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Sandwiched perfectly between CinemaCon and Cine Europe, CTCs podcast team have recorded another full length episode! Host Mike Bradbury is once again joined by regulars Kevin Markwick and Toni Purvis along with special guest Rob Younger from the Parkway Cinema in Barnsley to talk about the renaissance of 35mm and 70mm film, preparing for Avatar: Fire and Ice and server speeds.
In today's episode, we feature reports on the Supreme Court's order to liquidate Bhushan Power and Steel, affecting JSW Steel's acquisition plans. Apple diverts India-made iPhones to the US, and Adobe CEO's insights on India's creator economy. There's also a revival of Amaravati as a green capital project and an increase in corporate NPS as employees shift to the new tax regime. Plus, MC Insider covers unusual boardroom gossip, including chapatis in CTCs and a wedding-turned-warfare.
The Joint Readiness Training Center is pleased to present the ninety-first episode to air on ‘The Crucible - The JRTC Experience.' Hosted by the LTC Westly “West” LaFitte, the Brigade Executive Officer Observer-Coach-Trainer for Brigade Command & Control on behalf of the Commander of Ops Group (COG). Today's guests are two other senior members of BC2, MAJ David Pfaltzgraff and MAJ Marc Howle. MAJ Pfaltzgraff is the BDE S-3 Operations OCT and MAJ Howle is the Senior Engineer / Protection OCT for BDE C2 (BDE HQ). In this episode, we focus on the military decision-making process (MDMP) and the common pitfalls that units encounter when executing it during large-scale combat operations (LSCO). A central theme is the misconception that skipping or abbreviating MDMP steps saves time, when in reality, it creates gaps in mission analysis, weakens course of action (COA) development, and leads to incomplete wargaming. The discussion highlights how units often struggle due to a lack of experience, insufficient staff training, and the failure to apply MDMP rigorously before arriving at combat training centers (CTCs). The speakers emphasize that effective planning is not just about following doctrine but also about ensuring that the process remains disciplined and repeatable under stress. Additionally, they discuss the importance of parallel planning and how mismanaging transitions between planning and execution can derail operations. The episode also explores the integration of staff members across warfighting functions to improve MDMP execution. It stresses that commanders must empower their staffs to conduct deliberate planning rather than relying on directed COAs that bypass critical analysis. A key takeaway is the role of noncommissioned officers in the planning process—often overlooked, their experience and tactical awareness are invaluable in refining mission details and ensuring feasibility. The conversation highlights the need for clear transition points between planning and current operations, ensuring that staff handoffs are seamless and do not disrupt tempo. Ultimately, the discussion underscores that MDMP is a leadership challenge requiring constant refinement, disciplined adherence to doctrinal steps, and a commitment to training at home station to build the repetitions necessary for success in LSCO. Part of S01 “The Leader's Laboratory” series. For additional information and insights from this episode, please check-out our Instagram page @the_jrtc_crucible_podcast Be sure to follow us on social media to keep up with the latest warfighting TTPs learned through the crucible that is the Joint Readiness Training Center. Follow us by going to: https://linktr.ee/jrtc and then selecting your preferred podcast format. Again, we'd like to thank our guests for participating. Don't forget to like, subscribe, and review us wherever you listen or watch your podcasts — and be sure to stay tuned for more in the near future. “The Crucible – The JRTC Experience” is a product of the Joint Readiness Training Center.
ANGLE PLC (AIM:AGL, OTCQX:ANPCY) Chief Executive Andrew Newland talked with Proactive's Stephen Gunnion about the company's recent breakthrough in dual ctDNA and CTC DNA analysis on the Illumina platform. The six-month project overcame technical hurdles to achieve an end-to-end solution using Illumina's specialist lung cancer DNA kit, demonstrating its potential impact in a 27-patient study. Newland highlighted that ANGLE's Parsortix system identified actionable DNA variants in circulating tumor cells (CTCs) that were not present in ctDNA samples. This advancement underscores the importance of analysing intact cancer cells rather than focusing solely on fragmented DNA. He also noted that Illumina has allocated its upcoming European Association of Cancer Research conference webinar to ANGLE's findings, marking the start of a co-marketing initiative. On the relevance of artificial intelligence (AI), Newland explained how it is used in analysing proteins on cells and molecular signatures, emphasising that the best possible sample, like Parsortix-based ones, is key to maximising the impact of AI and sequencing in liquid biopsies. For more insights, visit Proactive's YouTube channel, and don't forget to like, subscribe, and enable notifications to stay updated." #ANGLEPLC #LiquidBiopsy #CancerResearch #IlluminaCollaboration #Parsortix #CTCDNA #LungCancer #ArtificialIntelligence #MedicalBreakthrough #BiotechInnovation
Back together and in-person, CTCs podcast team combined to bring a new episode! Recorded during the Norwegian Cinema Conference in Lillehammer, host Mike Bradbury is joined by regulars Kevin Markwick and Toni Purvis along with special guests Tim Potter (Trigage) and Lillebjörn Gyllfeldt (Cinema Design in Sweden) to talk about whether technology alone can drive movie-goers to the box office, environmental sustainability in exhibition and how cinemas should be preparing for 2025 and beyond from a equipment stand point.
Watch the after show on Patreon: https://patreon.com/dannyjones Dr. Ronald Mallett is a physicist who is developing a time machine using ring lasers. Dr. Mallett also studies black holes, relativistic astrophysics, and quantum cosmology. SPONSORS https://zbiotics.com/danny - Use code DANNY for 15% off your order. https://meundies.com/dannyjones - Get 20% off + free shipping. https://shopmando.com - Use code DANNY for $5 off your starter pack. https://whiterabbitenergy.com/?ref=DJP - Use code DJP for 20% off EPISODE LINKS Time Traveler book: https://a.co/d/bGJIAQT https://twitter.com/RLMallett FOLLOW DANNY JONES https://www.instagram.com/dannyjones https://twitter.com/jonesdanny OUTLINE 00:00 - Einstein's basis for time travel 10:21 - Forward vs. backwards time travel 22:59 - How GPS satellites time travel 30:40 - The illusion of time 38:04 - Black holes 52:49 - Creating closed time curves (CTCs) 54:54 - How light can affect time; the ring laser 01:05:20 - How to build a time machine 01:15:06 - Limitations of time travel 01:28:32 - Dr. Ronald Mallet's motivation for time travel research 01:33:57 - Quantum mechanics vs. block universe 01:46:26 - Secret research program on time travel 01:55:45 - Evolution of technology 02:01:21 - UFOs 02:13:18 - Fighting deception with science 02:21:03 - Brain filters & living in a simulation Learn more about your ad choices. Visit megaphone.fm/adchoices
The Joint Readiness Training Center is pleased to present the sixty-eighth episode to air on ‘The Crucible - The JRTC Experience.' Hosted by the former Commander of Ops Group (COG), COL Matthew Hardman. Today's guest is the Commanding General of the Joint Readiness Training Center and former COG, BG Jason Curl. BG Curl commissioned as an infantry officer from the United States Military Academy in 1995 and has served in a variety of maneuver assignments. As the CG at the Joint Readiness Training Center, he has the Hollywood call-sign of “Warrior 06.” In this episode, we dive into the pivotal role combat training centers (CTCs) play in preparing brigade combat teams (BCTs) and divisions to fight and win on tomorrow's multi-domain battlefield. The CTC experience is a crucible, pushing units to their limits and refining their warfighting skills through realistic, high-intensity scenarios that mirror the complexity of modern warfare. We explore how these rigorous training environments shape the collective glidepath of readiness, fostering adaptability, cohesion, and mastery across land, air, sea, cyber, and space domains. Join us as we discuss how the lessons learned at CTCs are crucial for future mission success. Additionally, we highlight some of the modernization and innovation efforts that have been incorporated into our rotational design as well as some of the modernization of our rotational training units. Part of S01 “The Leader's Laboratory” series. For additional information and insights from this episode, please check-out our Instagram page @the_jrtc_crucible_podcast Be sure to follow us on social media to keep up with the latest warfighting TTPs learned through the crucible that is the Joint Readiness Training Center. Follow us by going to: https://linktr.ee/jrtc and then selecting your preferred podcast format. Again, we'd like to thank our guests for participating. Don't forget to like, subscribe, and review us wherever you listen or watch your podcasts — and be sure to stay tuned for more in the near future. “The Crucible – The JRTC Experience” is a product of the Joint Readiness Training Center.
The responsibility for recruiting, training and retaining US Army soldiers sits on the shoulders of the Sergeant Major of the Army; a job in which there is no training course and where experience is the defining factor. To break down what the Sergeant Major of the Army does, the current state of the Army, and where the Army is headed, Fran Racioppi traveled deep into the center of the Pentagon for a conversation with Sergeant Major Mike Weimer, the 17th Sergeant Major of the Army and the first Green Beret selected for the role. The SMA defined professional warfighting and the importance of an all volunteer force. He broke down the art and science relationship between commissioned and non-commissioned officers. He shared how his experience in the Special Forces shadows prepared him for the limelight of the SMA role. And they talked about the future, including his vision for solving the recruiting challenge, how warfare is evolving from the kill chain to the kill web, how he's planning to retain the right people, and how the integration of Special Operations and the regular Army is more important now than ever. Highlights:0:00 Introduction2:53 The Army is busy 3:52 The Professional Warfighter11:40 People are the Army's weapons system 15:53 The relationship between Commanders and NCOs22:24 SMA Weimer's transition from the shadows25:55 The Army's recruiting challenges34:51 CTCs and the Kill Web40:12 Retaining the best and brightest43:50 Integrating Special Forces and the regular Army50:36 The Army's biggest opportunity52:17 Daily Foundations to SuccessQuotes: “Those that are committed, I remind them; the audio and video has got to match.” “All of the services are platform centric. The Army's platform is its people.” “The non-commissioned officer is the asymmetric advantage.” “The things that are usually the hardest in life are the things that are usually the most rewarding.” “Whatever you've done prior to coming into this seat is how you've prepared.” “We're on track to make our numbers this year….We need those numbers to be higher in upcoming years.” “I have a fair amount of combat…I've never been to war.” “You don't necessarily get do-overs in the fight that we're preparing for now.”“It's not just about retaining people; it's about retaining the right people.”“Standards and discipline can't just be some whimsical thing we throw around.”Take a listen, watch, or read our conversation with the Army's most senior non-commissioned officer, then head over to our YouTube channel or your favorite podcast platform to catch up on our entire national security series from Washington, DC and Fort Liberty, NC. The Jedburgh Podcast and the Jedburgh Media Channel are an official program of The Green Beret Foundation. Learn more on The Jedburgh Podcast Website. Subscribe to us and follow @jedburghpodcast on all social media.
The Joint Readiness Training Center is pleased to present the sixty-second episode to air on ‘The Crucible - The JRTC Experience.' Hosted by the Commander of Ops Group (COG), COL Matthew Hardman. Today's guests are a pre-command and incoming commander for 2nd Brigade Combat Team of 10th Mountain Division (Light Infantry), COL Anthony Gore and the current commander of 1st Brigade Combat Team of the 101st Airborne Division (Air Assault), COL Trevor Voelkel. Established during the build-up of US forces in the Cold War, 2nd BCT / 10th MTN has been continually deployed in support of various contingencies around the world as well as six deployments during the Global War on Terror. They have the Hollywood call-sign of “Commando” and the motto of “Courage & Honor.” 1st BCT / 101st ABN started life as 327th Infantry Regiment in WWI and then came to the 101st ABN as a Glider Infantry Regiment. They are one of the most storied infantry brigades in the US Army, having fought in WWI, WWII, Vietnam, Op Desert Storm / Gulf War, and continuously during the GWOT. They have the Hollywood call-sign of “Bastogne” and the motto of “Honor & Country.” In this episode we discuss developing leaders at echelon within our brigade combat teams for the next looming fight. Developing leaders at echelon within BCTs is essential for preparing our force to effectively navigate the complexities of large-scale combat operations across multiple domains. This development begins with comprehensive training programs that emphasize the integration of multi-domain capabilities, ensuring leaders understand how to coordinate and leverage assets across these domains. Leaders must be proficient in multi-domain operational planning and execution, capable of making informed decisions in high-pressure environments. Training scenarios at home-station should replicate the intensity and unpredictability of LSCO as seen at the CTCs, fostering adaptability, resilience, and innovative problem-solving skills. Additionally, leadership development must focus on enhancing communication and collaboration skills, enabling leaders to work seamlessly with joint and coalition forces. By investing in robust leadership training and fostering a culture of continuous learning, BCTs can cultivate a cadre of leaders who are well-prepared to face the dynamic challenges of modern warfare and effectively command operations across multiple domains. Part of S02 “If I Would Have Only Known” series. Be sure to follow us on social media to keep up with the latest warfighting TTPs learned through the crucible that is the Joint Readiness Training Center. Follow us by going to: https://linktr.ee/jrtc and then selecting your preferred podcast format. Again, we'd like to thank our guests for participating. Don't forget to like, subscribe, and review us wherever you listen or watch your podcasts — and be sure to stay tuned for more in the near future. “The Crucible – The JRTC Experience” is a product of the Joint Readiness Training Center.
The Joint Readiness Training Center is pleased to present the fifty-third episode to air on ‘The Crucible - The JRTC Experience.' Hosted by the Commander of Ops Group (COG), COL Matthew Hardman. Today's guest is Director of Operations Research Center at the U.S. Military Academy at West Point, LTC David Beskow, PhD. He has a PhD in Societal Computing from Carnegie Mellon University School of Computer Science and serves in the Department of Systems Engineering. The Operations Research Center (ORCEN) provides a dedicated analytical capability that engages problems of national significance for the purpose of enriching cadet education, enhancing the professional development of Operations Research Systems Analysis Officer Faculty, integrating emerging technologies and analytical tools into the Academic Program, and sustaining ties between the Academy, the Army, and the Department of Defense (DoD). The United States Military Academy (USMA) is a United States service academy in West Point, New York. It was originally established as a fort during the Revolutionary War, as it sits on strategic high ground overlooking the Hudson River 50 miles (80 km) north of New York City. It is the oldest of the five American service academies and educates cadets for commissioning into the United States Army. In this episode we continue to discuss warfighting on the modern battlefield, the incorporation of technology as a combat multiplier, and preparing the force for AI centric warfare of the future. Specifically, we discuss using data to feed intelligence and the operations process as well as how the Army is planning to incorporate emerging technologies into its formations on the modern battlefield. We also look at the application of machine learning to sift through massive amounts of data to find the nuggets of key information, classify it, and then start to do predictive analysis. LTC Beskow's department has been tasked to look at: How do we become more data enabled as a fighting formation? How can we better utilize technology, especially ML/AI? Do we have the right systems in place to collect the data to feed ML/AI? If not, what methodology would you recommend? For the CTCs like JRTC, his team is looking at: What data do the CTCs produce that the Army could leverage? What changes to the collection requirements would you recommend that would be least impactful from a collection process but be massively impactful to the Army at large? How can we better use the data? Understanding human performance, streamlining our acquisitions, better utilization of ML/AI, etc. Part of S01 “The Leader's Laboratory” series. For additional information and insights from this episode, please check-out our Instagram page @the_jrtc_crucible_podcast Be sure to follow us on social media to keep up with the latest warfighting TTPs learned through the crucible that is the Joint Readiness Training Center. Follow us by going to: https://linktr.ee/jrtc and then selecting your preferred podcast format. Again, we'd like to thank our guests for participating. Don't forget to like, subscribe, and review us wherever you listen or watch your podcasts — and be sure to stay tuned for more in the near future. “The Crucible – The JRTC Experience” is a product of the Joint Readiness Training Center.
The following guest sits down with host Justin White:• Mahb Rahman – Mortgage Broker, Safetrust MortgageHow a Mortgage Broker Shop is Scaling by Prioritizing a Streamlined Operations ProcessWhile many mortgage loan originators aim for operational efficiency, Safetrust Mortgage is building its company on operational excellence. How is Safetrust impressing clients and referral partners with a smooth and speedy loan process? Listen to Episode #66 of Good. Better. Broker. as we talk with Chief Growth Officer, Mahb Rahman, about their strategy to scale by doing all the basics exceptionally well.In this episode of the Good. Better. Broker. podcast, you'll learn how a growing mortgage company is spearheading its growth with its Operations team.In this episode, we discuss ...• 1:29 – Mahb's move to becoming an independent mortgage broker• 2:45 – Why Safetrust Mortgage built their company on having a strong Operations team• 4:11 – How Safetrust has structured their process to align with their vision• 6:25 – How Mahb's prior experience helped him streamline the company's process• 8:02 – Why delegating parts of the loan process fosters accountability and collaboration• 10:14 – The advantage of having an experienced Operations team• 13:07 – How Safetrust leverages their Operations team to impress real estate agents• 16:45 – The importance of posting fast CTCs on social media• 19:16 – How Safetrust plans to grow with Operations continuing to lead the wayShow Contributor:Connect on LinkedInConnect on FacebookConnect on InstagramJustin White is UWM's in-house brand journalist and the host of the daily news video, Inside Pass. He creates engaging content across multiple platforms to promote the benefits of the wholesale channel and partnering with UWM. A seven-time Emmy-award winner, Justin is a graduate of the S.I. Newhouse School of Public Communications at Syracuse University.Connect with Justin on LinkedIn, Instagram or TwitterConnect with UWM on Social Media:• Facebook• LinkedIn• Instagram• Twitter• YouTubeHead to uwm.com to see the latest news and updates.
The treatment and management of patients with multiple myeloma is continually evolving, giving rise to novel prognostic tools and therapeutic... The post Unanswered questions regarding the sequencing of BCMA therapies, the prognostic value of CTCs & the growing role of quadruplets appeared first on VJHemOnc.
The Joint Readiness Training Center is pleased to present the thirty-sixth episode to air on ‘The Crucible - The JRTC Experience.' Hosted by the Commander of Ops Group (COG), COL Matthew Hardman. Today's guest are Today's guests are all seasoned Observer-Coach-Trainers from across Operations Group, MAJ(P) Drew Zabriskie, MAJ Westly “Wes” LaFitte, and MAJ James Lee. Our guest observer-coach-trainers with nearly fifty decisive action training environment rotations between them. MAJ(P) Drew Zabriskie (L05) is the BSB Executive Officer OCT for TF Sustainment (BSB / CSSB / DSSB) with ten rotations. MAJ Westly “Wes” LaFitte is the BN Executive Officer OCT for the Fires Support TF (Field Artillery BN). MAJ James Lee is the BDE S-3 Operations Officer OCT for the BDE Command & Control (BCT HQ). (MAJ(P) Zabriskie would become LTC Zabriskie a few short weeks post filming and MAJ Lee would become the BDE Executive Officer for BC2 as well.) In this episode we discuss the lessons learned from field grade officer perspective in preparation for conducting large scale combat operations across multiple domains. The panel discusses large scale combat operations executed at the battalion, brigade, and division echelons, offering perspectives on a variety of topics including combined arms maneuver, transparent battlefield, fires, and contested logistics as well as emerging technologies employment. Key lessons learned for field grade leaders at all echelons are understanding the amount of control and influence leaders must exert to be effective, grasping what you can't control and not wasting resources in pursuit of it, understanding your area of operations and your sphere of influence within it, and lastly understanding the systems which drive all of these is critical. The goal for leaders at all echelons must be to ensure that you're not creating problems than you're solving for your subordinates as well as your higher headquarters. Embracing the “teamwork makes the dream work” philosophy and striving to work together as a team across the brigade combat team. The number one question that commanders and staff ask across the force is how can we get better at the military decision making processes (MDMP)? There's no shortcut, it's simply sets and repetitions that make staffs better at MDMP. The largest myths that most field grade officers have when coming to JRTC is that as the “Iron Major” for their echelon that they can't or won't fail at any time. The combat training centers have been described as the “Ranger school for command teams and staffs.” With that in mind, every organization that comes to the CTCs is destined to fail by design. It is only through failure that growth can occur. Part of S01 “The Leader's Laboratory” series. Don't forget to checkout our annual Large Scale Combat Operations Symposium, episode 16 and episode 30 of ‘The Crucible.' Be sure to stay to for a follow-up episode with the company team OCTs from LSCO Symposium of '23. For additional information and insights from this episode, please check-out our Instagram page @the_jrtc_crucible_podcast Be sure to follow us on social media to keep up with the latest warfighting TTPs learned through the crucible that is the Joint Readiness Training Center. Follow us by going to: https://linktr.ee/jrtc and then selecting your preferred podcast format. Again, we'd like to thank our guests for participating. Don't forget to like, subscribe, and review us wherever you listen or watch your podcasts — and be sure to stay tuned for more in the near future. “The Crucible – The JRTC Experience” is a product of the Joint Readiness Training Center.
CTCs podcast team are on the road at the Norwegian Film Conference recording a brand new episode. Publican Mike Bradbury is once again joined by regulars Kevin Markwick and Toni Purvis and special guest Orjan Taule (MD of Unique Digital Cinema Norway). In this episode the team talk about intermissions in the wake of Killers of the Flower Moon, masking, tabs and ambient light and also discuss the concerns around content security and impending critical updates to servers.
The Joint Readiness Training Center is pleased to present the thirty-fourth episode to air on ‘The Crucible - The JRTC Experience.' Hosted by the Commander of Ops Group (COG), COL Matthew Hardman. Today's guest is the Commanding General of the 82nd Airborne Division, MG Christopher LaNeve (All American 06). He was previously the Commander of Ops Group from 2015 to 2016. The 82nd Airborne Division was founded after the American entry into World War I in August 1917 as part of the American Expeditionary Forces. They were redesignated as an airborne division in February 1942 have taken part of every conflict since WWI with the exception of the Korean War. The 82nd Airborne DIV is an airborne infantry division of the U.S. Army specializing in joint forcible entry operations via vertical envelopment, both airborne and air assault, into denied areas with a U.S. Department of Defense requirement to respond to crisis contingencies anywhere in the world within 18 hours. They have the Hollywood call-sign of “All American” Division and the motto of “In Air, On Land.” In this episode we discuss what an airborne infantry division needs to not only survive but succeed on the modern battlefield, conducting large scale combat operations. All American 06 frames the conversation by highlighting the importance of the training offered at the three Combat Training Centers as well as the training that is required to ensure that the Army is prepared to fight and win on tomorrow's battlefield. Divisions can prepare their brigades to a fair degree of readiness through their intensive training cycles but simply cannot train a brigade combat team plus attachments against a free-thinking opposing force to scale in time and space. The CTCs are where our Force is able to test new tactics, techniques, and procedures in a realistic operating environment. XVIII Airborne Corps, their higher headquarters, had tasked 82nd ABN to structure itself and then test it as a unit under the ‘Division of 2030' concept. The division has restructured itself where the 82nd Airborne Division Artillery (DIVARTY) is the brigade headquarters for each of the field artillery battalions within the division as well as the 82nd Airborne Division Sustainment Brigade is the brigade headquarters for each of the brigade support battalions. This has allowed the Division to focus on “push” style logistics instead of “pull” style logistics that were common over the last twenty years supporting the Global War on Terror. The testing has identified that the DIVARTY needs a BSB itself just like the traditional infantry IBCTs. The Division has also been able to test their mobile assault command posts, making them not only more robust but streamlining to being smaller in-size while being more mobile and thus more survivable. All American 06's goal: “Uncomfortably light, increasingly lethal” for his formations. His guidance to company through brigade commanders on their command posts has been: Must have both a digital & analog common operating picture Must establish & maintain communications Employ effective & timely joint fires Goal of displacing in under five minutes Part of S01 “The Leader's Laboratory” series. Don't forget to check-out XVIII Airborne Corps' social media pages, their handles are ‘XVIII Airborne Corps' on Facebook, ‘18airbornecorps' on X, and ‘18thairbornecorps' on Instagram. For additional information and insights from this episode, please check-out our Instagram page @the_jrtc_crucible_podcast Be sure to follow us on social media to keep up with the latest warfighting TTPs learned through the crucible that is the Joint Readiness Training Center. Follow us by going to: https://linktr.ee/jrtc and then selecting your preferred podcast format. Again, we'd like to thank our guests for participating. Don't forget to like, subscribe, and review us wherever you listen or watch your podcasts — and be sure to stay tuned for more in the near future. “The Crucible – The JRTC Experience” is a product of the Joint Readiness Training Center.
A new review paper was published in Oncotarget's Volume 14 on August 10, 2023, entitled, “Peripheral surrogates of tumor burden to guide chemotherapeutic and immunotherapeutic strategies for HPV-associated malignancies.” With the rapid adoption of immunotherapy into clinical practice for HPV-associated malignancies, assessing tumor burden using “liquid biopsies” would further our understanding of clinical outcomes mediated by immunotherapy and allow for tailoring of treatment based on real-time tumor dynamics. In their new review, researchers Meghali Goswami, Jeffrey Schlom and Renee N. Donahue from the National Cancer Institute examine translational studies on peripheral surrogates of tumor burden derived from peripheral blood in HPV-associated malignancies, including levels and methylation of circulating tumor DNA (ctDNA), miRNA derived from extracellular vesicles, circulating tumor cells (CTCs), and HPV-specific antibodies and T cell responses. “We review their utility as prognostic and predictive biomarkers of response to chemotherapy and radiation, with a focus on how they may inform and guide immunotherapies to treat locally advanced and metastatic HPV-associated malignancies. We also highlight unanswered questions that must be addressed to translate and integrate these peripheral tumor biomarkers into the clinic.” DOI - https://doi.org/10.18632/oncotarget.28487 Correspondence to - Jeffrey Schlom - schlomj@mail.nih.gov Video short - https://www.youtube.com/watch?v=b9FhlVB6iY0 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28487 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, HPV-associated malignancies, immunotherapy, circulating tumor DNA, circulating tumor cells, HPV-specific antibodies About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
CTCs podcast team are back for a whole new feature length episode. Publican Mike Bradbury is once again joined by regulars Kevin Markwick and Toni Purvis and special guest Cinematographer Nic Knowland (best known for his work on movies including Institute Benjamenta, or This Dream People Call Human Life (1995), Berberian Sound Studio (2012) and The Duke of Burgundy (2014)). In this episode the team get insights in to the creative process and why the differences between what the film maker intended and what's shown on screen matters, they discuss HDR and the lack of standards, the magic of cinema, audio description technology and much more.
A new research paper was published in Oncotarget's Volume 14 on July 20, 2023, entitled, “Development of a multiplex assay to assess activated p300/CBP in circulating prostate tumor cells.” Reduced SIRT2 deacetylation and increased p300 acetylation activity leads to a concerted mechanism of hyperacetylation at specific histone lysine sites (H3K9, H3K14, and H3K18) in castration-resistant prostate cancer (CRPC). In this new study, researchers Mikolaj Filon, Bing Yang, Tanaya A. Purohit, Jennifer Schehr, Anupama Singh, Marcelo Bigarella, Peter Lewis, John Denu, Joshua Lang, and David F. Jarrard from the University of Wisconsin examined whether circulating tumor cells (CTCs) identify patients with altered p300/CBP acetylation. “In the current study, employing a novel Exclusion-based Sample Preparation (ESP) technology (9) (Supplementary Figure 1) to isolate CTCs, we evaluated p300 activity, SIRT2 expression and H3K18 acetylation in CTCs in a series of patients with sensitivity or resistance to ADT.” CTCs were isolated from 13 advanced PC patients using Exclusion-based Sample Preparation (ESP) technology. Bound cells underwent immunofluorescent staining for histone modifying enzymes (HMEs) of interest and image capture with NIS-Elements software. Using the cBioPortal PCF/SU2C dataset, the response of CRPC to androgen receptor signaling inhibitors (ARSI) was analyzed in 50 subjects. Staining optimization and specificity revealed clear expression of acetyl-p300, acetyl-H3K18, and SIRT2 on CTCs (CK positive, CD45 negative cells). Exposure to A-485, a selective p300/CBP catalytic inhibitor, reduced p300 and H3K18 acetylation. In CRPC patients, a-p300 strongly correlated with its target acetylated H3k18 (Pearson's R = 0.61), and SIRT2 expression showed robust negative correlation with a-H3k18 (R = −0.60). A subgroup of CRPC patients (6/11; 55%) demonstrated consistent upregulation of acetylation based on these markers. To examine the clinical impact of upregulation of the CBP/p300 axis, CRPC patients with reduced deacetylase SIRT2 expression demonstrate shorter response times to ARSI therapy (5.9 vs. 12 mo; p = 0.03). A subset of CRPC patients demonstrate increased p300/CBP activity based on a novel CTC biomarker assay. “With further development, this biomarker suite may be used to identify candidates for CBP/p300 acetylation inhibitors in clinical development.” Read the full study: DOI: https://doi.org/10.18632/oncotarget.28477 Correspondence to: David F. Jarrard - jarrard@urology.wisc.edu Keywords: prostate cancer, circulating tumor cells, p300/CBP About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Sign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28477 For media inquiries, please contact: media@impactjournals.com.
CTCs podcast team are back for a whole new feature length episode. Publican Mike Bradbury is once again joined by regulars Kevin Markwick and Toni Purvis and special guest Graham Lodge (Sound Associates and CTC Vice President). In this episode the team talk about projector availability, energy savings, PLFs, intermissions and Kevin gets a red card!
Top 5 Most Read RNS's on Vox Markets for Wednesday 19th April 2023 1. Kistos Holdings #KIST - Agreement to Acquire Mime Petroleum A.S On completion, the acquisition will add 24 MMboe of 2P reserves and will also add over 2,000 boe/d of production immediately. Group production in 2023 will be in the range of 8,500 and 10,500boe/d. The consideration for the transaction is US$1 plus the issue of up to 6 million warrants exercisable into new Kistos ordinary shares at a price of 385p 2. Amigo Holdings #AMGO - Statement re. share price movement Amigo Holdings has noted the recent movement in the Company's share price and confirms that it knows of no reason for this increase. The board continues to implement the fallback solution, which is the orderly wind-down of the business, which is expected to result in no value attributable to shareholders once the wind-down is completed. 3. Angus Energy #ANGS - Finalisation of Management Changes & Options issue Further to the announcement of 2 March 2023 and Angus's vision of becoming a significant player in the aggregation, production and storage of gas, the Company is pleased to finalise the appointment of Richard Herbert as Chief Executive Director, George Lucan as Executive Chairman and Patrick Clanwilliam as Non-Executive Director. 4. Audioboom Group #BOOM - Q1 Trading Update Q1 revenue, in line with expectations, of US$15.4 million. This was, as expected, lower than Q1 2022 (US$19.5 million). Strong management and cost control enabled maintenance of profitable operations despite market conditions with Q1 adjusted EBITDA(1) profit of US$0.2 million. Group cash at 31 March 2023 of US$5.1 million (31 December 2022: US$8.1 million). 5. Angle #AGL - ANGLE announces partnership with BioView ANGLE announce it has signed an agreement with BioView to develop a liquid biopsy circulating tumor cell (CTC) HER2 assay for breast cancer utilising ANGLE's FDA cleared Parsortix® PC1 Clinical System to harvest CTCs and BioView's automated microscopy systems and software to detect and assess the HER2 expression and/or gene amplification in CTCs.
近期，国际顶级学术期刊 Cancer Cell的封面设计出现《西游记》中“三打白骨精”的一幕。当孙悟空（NKs）识破美丽的小女孩是由一心想吃唐僧肉的白骨精（CTCs）所变，并要尝试将其杀死时，白骨精会通过假装楚楚可怜唤起唐僧（血小板）的悲悯之心来保护她，猪八戒（HLA-E）也被唐僧误导，以致最后阻碍了对白骨精的制服。
JRTC is pleased to present this episode of ‘The Crucible.' Hosted by the Commander of Ops Group (COG), COL Matthew Hardman. Today's guest is the commander of 1st IBCT, 82nd ABN, COL Theodore Kleisner. In this episode they discuss some of the things that the Devil BDE would have liked to have known prior to the start of this LTP as well as how the CTCs prepare BCTs to succeed in modern warfare.
Top 5 Most Read RNS's on Vox Markets for Wednesday 2nd November 2022 5. Sabien Technology #SNT - Supply of UK's First Regenerative Green Oil System Sabien Technology provides an update on contract status with City Oil Field, Inc., of South Korea and b.grn Group, a previously announced special purpose vehicle 33% owned by Sabien. b.grn has today paid a fee to COF to formalise this contract. The Agreement is conditional on b.grn raising the required funding and entering into an EPC agreement within one year (unless mutually agreed to extend). 4. Angle #AGL - Multiple downstream analysis techniques for CTCs ANGLE announces the publication of results from a multi-centre clinical study undertaken that shows the Parsortix® system was used to enrich circulating tumour cells (CTCs) from 207 patients with metastatic breast cancer (MBC). 3. Alien Metals #UFO - Alien acquires 90% interest in Iron Ore Projects Alien Metals has given notice to exercise its option to acquire an additional 39% interest in the Hancock and Brockman direct shipping iron ore projects from Windfield Metals. 2. Hurricane Energy #HUR - Formal Sale Process, Capital Return & Ops Update Following receipt of an unsolicited offer and after a period of engagement with the bidder, Hurricane has received an offer at an indicative price of 7.7p. The Indicative Offer is at a premium of only 13% compared to the mid-market closing price of 6.8p on 1 November 2022. The directors of Hurricane have concluded that the Indicative Offer should not be recommended to shareholders. 1. Supply @ME Capital #SYME - Grant of Awards under Long Term Incentive Plan Following approval from the Company's board of directors and remuneration committee of the Board, on 31 October 2022 awards in the form of nominal-cost share options over 897,424,157 shares were granted under the Supply@ME Long Term Incentive Plan to certain of the Company's executives and senior management.
Josh Smith and Dustin Shoe recently attended ACC Media Day, where they got to ask Jon Scheyer, Jeremey Roach, and Jacob Grandison some questions about this year's team. Along with Raul Clement, they react to some of the clips they recorded and discuss the event as a whole. Then they look ahead to Countdown to Craziness and recount their favorite moments from CTCs past. On the next episode: Countdown to Craziness Reaction and Overanalysis To learn more about listener data and our privacy practices visit: https://www.audacyinc.com/privacy-policy Learn more about your ad choices. Visit https://podcastchoices.com/adchoices
Vortex Biosciences PLC's CEO Paul Jones explains the company's technology for capturing live circulating tumour cells (CTCs). One of NetScientific's portfolio companies, Jones says the next stage for developing the business is to build relationships with the pharmas and biotechs developing cancer therapies and support them with companion diagnostics. This will involve Vortex moving towards a CTC service providing lab-developed tests and in-vitro diagnostics, he says. #Vortex Biosciences #Netscientific
Intro: Even our lungs need a sense of purpose. Let Me Run This By You: Boz is buying a house!Interview: We talk to actor and documentary filmmaker Cullen Douglas about AMDA, Florida School of the Arts, Southeastern Theatre Conference, Tyne Daly, character actors, Jason Priestly, Patricia Crotty, Our Town, Lenny Bruce, Dick Van Dyke, investigative journalism, reusing caskets, David Carr, Deadwood, playing Bilbo Baggins, being pen pals with Andrea McCardle, singing If I Were A Rich Man, The Pirates of Penzance, Bye Bye Birdie, Robert Sean Leonard, Billy Flanigan: The Happiest Man on Earth, Shonda Rhimes, Twin Peaks, Grey's Anatomy , Barry, Bill Hader, documentary filmmaking, The Humanitas Prize, Private Practice.FULL TRANSCRIPT (Unedited): 1 (8s):I'm Jen Bosworth Ruez.2 (10s):And I'm Gina Paci.1 (11s):We went to theater school together. We survived it, but we didn't quite understand it.2 (15s):20 years later, we're digging deep talking to our guests about their experiences and trying to make sense of1 (20s):It all. We survived theater school and you will too. Are we famous yet?3 (33s):TikTok and I started looking at the videos and I was like, Ooh, I don't know about this. I think I need to start wearing wake up. So thank you. You1 (43s):Look gorgeous. How are3 (43s):You doing?1 (44s):Yeah, hi. I'm finally, Many things are happening. Many things are happening. So I finally, even though I'm coughing still little, I finally feel like I am, I like kicked the pneumonia bronchitis situation and little mostly thank you. I, yeah, I, we went away and then to Ventura and I slash Ojai and I really rested and I really, there was one day I worked, but I really mostly rested and I just really was like, okay, I need actual ass downtime. And yeah.1 (1m 25s):And then I started to heal and I was also on praise God for antibiotics. And then the thing that really helped me really kick it was I hadn't exercised my lungs in a really long time at all because I was so sick that I just was like, Who wants to like walk or, and, and it was 107 degrees, so it's like, who wants to exercise in that? So my cousin, my sister came in town, I, that's like a big eyebrow raise for, to drop my niece off to college. And we went on a hike to Griffith, but like a sloping hike, not a crazy hike. And I was like, I don't think I'm gonna be able to do it.1 (2m 5s):And it actually helped my lungs to like feel like they were contributing to fucking something and me like Forgot I3 (2m 16s):Like a sense of purpose. Right,1 (2m 17s):Right. And also like to, yeah, to have a job. And they were like, like to be exercised and I was like, Oh, I forgot that. Like the lungs. And, and it's interesting in this whole covid situation, like the lungs need to work too. And I never understood in hospitals, cuz I spent quite a long time in them, why they have those breathing like tube things that you blow the ball and the ball floats up. You have to, I thought that was so dumb until I had bronchitis and pneumonia and I was like, Oh, they have to work. Like they have to be expanded. If you don't use them and work them, they get, it's not good when,3 (2m 58s):When my dad, you know, my dad had this really bad car accident when I was like nine years old and yeah, he rolled 40 times and he wasn't wearing a seatbelt, which saved his life because he was in a convertible. But of course the reason he got into the accident was because he was drinking anyway. He broke everything. Like he broke six ribs and he had one of, he had to spend one year lying on an egg crate mattress on the floor one year. And for the rest of his life, every time he sneezed or coughed it hurt his ribs. But he,1 (3m 34s):Oh, and he3 (3m 36s):Had one of of those things like you're talking about. And as a child I could not get it to the height that I was supposed to go. I shuder to think what it would be like right now. Yes. So you're, that was a good reminder to exercise our lungs. I make sure my breathing capacity is good1 (3m 54s):And, and, and even wait and, and it's like, I always literally thought, oh, you exercise to be skinny. That is the only, only reason no other, like, if you had asked me, I'd say, Oh, there's no other reason. What are you talking about? But now I'm like, oh, these parts of us need actual exercising. Literally lie. I just, it blew my mind.3 (4m 19s):I was lies1 (4m 21s):The lies.3 (4m 22s):It's endless. Yes.1 (4m 27s):Hey, let me run this by you. Oh, I think we're buying a house. What? This is the craziest Oh my not in, Yeah. Okay. This is what went down. So this is so crazy. Miles' job stuff has evened out in terms of like, there's just so much going on that I can't talk about, but which is makes for terrible radio, but podcasting. But anyway, the point is we're we're a little stable, so we went to Ventura and I was like, I fucking love this town. I love Ventura. It's an hour away. It's a weird like, think lost boys, right? Like Lost Boys. The movie is, is really Santa Cruzi, but like, that's what this town reminded of.1 (5m 9s):It's not, so it's Adventurer county, so it's like an hour northwest. It's on the beach. And I was like, I love this town. I I I love it here. There's so many brown folk. It's heavily, heavily you Latina. And it's like, so anyway, I was like, I love it, but I bet I can't afford it like anywhere in California. Well it turns out that Ventura is about 500,000 less on a house than la. So I was like, wait, what? So we saw this darling house that was, that is was small but like beautiful craftsman and you know, I'll just say I'll be totally transparent with $729,000, which is still a shit ton of money.1 (5m 49s):But I looked at the same exact property almost in, in, in Pasadena for 1.3 million for two bedroom, one bath. Yeah. Two bedroom, one bath got preapproved. I've never been preapproved for anything in my goddamn light. We got preapproved for a mortgage. I couldn't, Gina, I couldn't. But when we got the preapproval letter, like I literally, speaking of lies, I was like, okay, well just expect him to come back and say we can't do anything for you.3 (6m 17s):Yeah, right.1 (6m 19s):Just really know it's not gonna work. And he wrote back and was like, Here's what we can do on this house the mortgage wise and it's comparable. It's in the ballpark of what we're paying in rent. And I was like, I don't wanna be going into my middle aged and later years in no space.3 (6m 39s):It really takes a toll. It really takes a toll on your psyche in a way that you can't really account for until you go from no space to having space. And then you go, oh my gosh, there's these three specific muscles in my shoulders that have been tense for the entire time I've been living in a city, you know, decades in some1 (6m 56s):Cases. So it's a whole different, I could build a little studio, like all the things. So yeah. So I'm grateful. Never would occur to me, never would have occurred to me. Never.3 (7m 6s):Do you care to say anything about your sister's visit?1 (7m 10s):Well, you know what is yes. And what is so comforting to me again, you know, if you listen to this podcast you're like, Oh my god, Jen, shut up. But about the truth. Okay. The truth is the fucking truth of, and even, even if it changes from person to person, that person's truth is the truth. And my truth is, I feel, So she came and she stayed not with me because I just, that what we were outta town. And then she stayed in my house while we were gone, which was fine with her, with my niece for one night. And then I saw her one day and that was, that was fine. And then she stayed with my cousin and it was, let's just say it was very, the, for me, my experience was, oh, someone else besides me sees the challenges.1 (7m 60s):And that's what I will say about that. There is something about being witnessed and having someone else go. I see, I feel what you're talking about.3 (8m 11s):Yes. Oh, I, I relate very deeply to that because people who are good at1 (8m 19s):Image image management,3 (8m 22s):At image management, a term I like is apparent competent.1 (8m 26s):Oh yes. Oh yes. I love that. I've never heard that. Apparent, competent. That is it.3 (8m 30s):Yes. Many, many people in life are apparently competent because all of their energy and effort goes into projecting very much just that idea and to be at home with them is a completely different thing. And I'm not saying like, Oh, you should always be competent in all areas of life or that I'm competent in all areas of life. I'm just saying like, yeah, there, there are some, some forms of personality disorders and just like, not even that, but just interpersonal problems are so kind of covert. And they're so, because I feel like people say, I feel like people are always trying to look for like the most broad, you know, big actions to determine whether somebody is1 (9m 13s):Whatever, nurse, whatever. They haven't been hospitalized, they've never been in rehab, they still have a house. You're like,3 (9m 20s):What? It's the same kind of mentality that says if you're not like in the gutter with a, with a mad dog in a paper bag that you're not an alcoholic, you know, it completely ignores probably what 85% of alcoholic for, which is highly functioning Correct. People who don't miss work and Correct. You know, maybe even people in their lives would never, ever know that they had a drinking problem. So yeah. So that is validating. I'm happy that for you, that you had that experience and sometimes it takes like 20, 30 years to get that validation. But the truth always, I mean, you know, it's true. That's the thing. It comes to the surface eventually.1 (9m 56s):Well, and the other thing is, I now as where I used to be so afraid of the truth and I still am, look, I I don't like getting, we know this about me, my feedback is hard for me. I'm scared of all the things, but I used to run from the truth like nobody's business in my own ways. Now I sort of clinging to it as, wait a second, wait a second, what is the truth of the matter? Like what are the facts here? Because I feel like that is the only way for me to not get kaka go, go crazy. And it is comforting. I am comforted in knowing that. Like, it was interesting. So I also am taking a solo show, writing class, I'm writing a new solo show, my third one.1 (10m 41s):And I'm just started and I thought, let me take a class with the woman who I taught. I did the first one in oh four in LA with, anyway, but I was saying on Facebook, like I, I, I'm taking this class with Terry and she's magic and I'm so glad I'm doing it and da da da. And she was like, Hey, I have a question for you. Can I quote you? And I was like, Yes. Because in her, in her like, for a and I said, of course it's all true. Like I didn't have to worry that my quote was somehow dirty or misleading or like, not really what I felt like I've done that so much in my life in the past where I've been like, oh shit, I told them I loved them or I loved their stuff, or I loved and I feel inside totally incongruent with that kind of thing.1 (11m 30s):No, I was like, no, these are what, these are my words now. I try to, it doesn't always work, but I try to just be like, okay, like what is the truth? And if someone had to quote me, would I be okay? And I, and I am a lot of the time I was like, of course you can. It's what I, I'm thanking for asking, but also it's what I feel in my bones about that, that you, that you have a magic when it comes to solo show teaching. That's it, it that is the truth. That my,3 (11m 55s):That is so cool. It's cool that you're doing that and I'll, that it, that gave me a reminder I had wanted to say on this podcast because you know, we had Jeremy Owens on the podcast. Yes. And he recently put on his social that he, he was doing it kind of as a joke, but I think he's actually doing it now, which is doing another solo show. And I had messaged him to say, you know, I meant what I said when I told you that you should do this and that I would help you and that goes for anybody cuz I said, I've said that to a lot of people on this podcast. Like, if you need help, you know, if this conversation has reinspired in you, a desire to go and do this other creative thing, please, I'm not saying like, I'm gonna co-write it with you.3 (12m 37s):I'm saying like, let me know if there's something I can do, if I can read it or, or, or bounce it off of you so that that stands for any of our previous guests. But tell us more about what, what's it gonna be about, what are you gonna be talking about? Well,1 (12m 51s):I don't entirely know, but where I'm leading is, it was interesting in this, See the thing I forgot means is that I like writing exercises. I never do them on my own. I never do. So this, she does writing exercises and a meditation before and I really longed and craved that because I spend so much of my hustle these days. How can I bring in income? How can I advance my career in Hollywood? And that is really shuts down the play aspect of all things. And I'm not saying, you know, I'm not saying that you, that I I'm not saying it's bad. All I'm saying is it totally eliminates for me the create like the really raw fun play creativity.1 (13m 37s):Okay? So in this, in this class, I just took it like, I just took the class. I was like, I'll do it. It's a masterclass in solo work, I'll do it. I like her. She called me, I was on the freeway and I was like, I'll do it. So right now the working title is, and also a solo show more or less. And I don't know if that's gonna change, but it is. Like I, and, and then in the exercise we did, we had our first class Sunday, it was all about, I realized that this solo show needs to be for me more of a call to action that that we, the, and it really comes from something you said, which is, I'm paraphrasing, but it's like we are our only hope, which is the good news and the bad news.1 (14m 25s):So like you said, we are the problem, I am the problem. Which is great. And also the, you know, terrible. So that is sort of this solo show is more gonna be about, it's like more activism based, but in a like creative arts activism way and, and not just a funny antidotes about my wacky family. And I mean, I would argue we could argue that like that my last solo show did have that underneath. But I think there needs to be a more like call to action for artists and people like us to start doing the things in the arts world that are gonna like help save the planet. And I don't know what that means yet, but she was like, oh this is like more of an activism piece based on what you're like it has that component to it.1 (15m 11s):And I was like, yeah. And then she said, if there was a banner, we did these cool exercise, she said, there's a banner all over town, whatever town you're in advertising your show, what would it say? And what came to mind in the meditation was it would be a red banner and it would just say, and it would say hope. And then in parentheses it would say sort of, So what I realized is I'm obsessed with the parentheses, like that's where I live. So I live in the world of I love my life parentheses, it's a fucking nightmare. So I love that kind of thing in my writing. And so I was like, okay, I'm really gonna embrace that. So it's like, it's like that, that stuff, I don't know where it's gonna go. I don't know what it's gonna happen.3 (15m 52s):Well two things. One is you have actually thrown out quite a few excellent titles for show, for solo shows. You'll periodically be like, that's the title of my new book or that's the title of my next, my next solo show. Yeah. So you might have to give a little re-listen to some episodes. I wish I could tell you which1 (16m 11s):I will.3 (16m 12s):Okay. The other thing is something that just came up for me when you said about the parenthesis, which I know exactly what you're talking about. I was saying like, oh yeah, she wants to show the good, the bad and the ugly. Oh. And something that occurred to me was like this concept of underbelly. Like you're showing yes, your soft underbelly. We are, I mean when I think when a person is maturing into themselves, that's what, that's the goal is to get to first accepting your own soft underbelly and then also contending with it and then representing it to the world. Because the thing that I've been on recently is like I have done myself and nobody else any favors for the amount of time I've spent misrepresenting myself because my misrepresenting myself has all been based on the lie that I thought there is a person that you are supposed to be, and your job is to be that person and you know, instead of like figure out the person that you are.3 (17m 10s):So, you know, coming into your own power is, is is a lot what we spend, what I spent my thirties about, like coming into your own power and not say that I arrived at it, but that No,1 (17m 23s):But3 (17m 24s):You about that. And then I think my forties are more about coming into my own vulnerability and that both of those things are really two sides of the same coin. Your power and your vulnerability, right? Because you can't have any power unless you're being honest about, you know, what the situation is. Today we are talking to Colin Douglas. Colin Douglas is an actor, writer, director, and documentary filmmaker who has been on absolutely everything. Most recently you've seen him on Barry and I love that for you.3 (18m 4s):But he's been, I joke in the, in our interview that he's been an absolutely every television show ever made. And that's only a slight exaggeration. He's been on Grey's Anatomy and Private Practice and the 2017 revival of Twin Peaks Agents of Shield, Pure genius. He's just been on everything Deadwood. So he's very experienced, he's very wise and he's very warm. So I hope you enjoy our conversation with Colin Douglas.0 (18m 34s):Great.3 (18m 36s):So congratulations Colin Douglas, you survived theater school. You survived4 (18m 42s):Two3 (18m 42s):Theater schools as a matter of fact.4 (18m 45s):I did. I was a glut for punishment actually. Yes. I I couldn't get enough of it.3 (18m 50s):So it was a BFA and MFA both in acting?4 (18m 54s):No, you know what, it was a zero degree. I, I am still just kind of riding by the seat of my pants. I actually, when I attended amda, it was not a degree program yet. Now it is. But back in the day it was basically they just kind of said, okay, go audition. And then when I went to Florida School, the arts, it only had an AA degree and I literally am still to this day two credit shy of my degree because I had booked a job out of Sctc and it was gonna be starting and I was like, I'm not sitting around and getting my degree just so that I can go get a job.4 (19m 42s):So I went, I took the job and I never looked back.1 (19m 45s):I mean that is, here's, I was just talking to someone who went to the theater school last night, my friend Lindsay. And we were talking about how conservatory I wish, I wish that I had done things differently, but it is what it is. But what you are reminding me of just go and audition is like the most valuable piece of advice anyone could have given us, which we never got. Which was now you, the piece of paper that says you have a BFA is not for not, but it's also not, it doesn't directly correlate to getting jobs. Like, it just doesn't. So you, you got a job while you were in school and said, I'm going, you didn't even think about staying or how did that work in your brain?4 (20m 30s):Well it was, it was because I was literally just the two credit shy kind of thing. And actually the class was, it was sort of a lab where I, you know, I had to help strike sets, but I was so busy with doing shows that I never had time to go help out with strike. So it was one of those things, oh okay, I'll, I'll require, I'll get that when I can get it when I have the time. And I never did. And then the tour was starting before the fall session started and I was like, you know what? My only regret honestly was the fact that I felt like, and, and again, it's not, you know, if somebody were to ask me today, you know, should you go to theater school?4 (21m 16s):I would say yes, if that's what really where you wanna hone your craft if you wanna, you know, build your community, but don't, if you're gonna do something like that, go to a program that has an established alumni because that's where your connections are being made when you get out of school is that support network that you have at amda at the time, there really wasn't, you know, when I was there, the biggest sort of claim to fame at the time was Time Daily. She was a graduate of, of Amda. And so it was, it wasn't as if I could reach out to Time Daily all of a sudden.4 (21m 59s):And then Florida School, the arts was, and still is such a small arts school that there really wasn't anybody for me to reach out to. Had I gone to Northwestern, had I gone to Juilliard or Yale or, or or Tish, that I would've had a built-in network of working professionals on the outside. So that was my only regret in that, that if I had perhaps gone to a different theater school, maybe I would've had those connections. But I certainly got the education I felt I needed.3 (22m 34s):Well and also you got the connections while getting paid instead of having to pay, which is was just definitely preferable. And by and speak about, you know, work experience and getting connections. You have been on every television show that has ever existed and tons of films too. So was your experience that as soon as you started working, you were just off to the races? I mean, I'm not suggesting that it's easy because no life of an actor is easy, but have, has it been pretty consistent for you would you say for your career?4 (23m 10s):It's been consistently inconsistent in that,1 (23m 16s):Wait, I just have to say that has to be the name of your book. Okay. I, we were talking about earlier before you got on about titles of shows and books, your book could be consistently inconsistent. The Culin Douglas story, I'm just, I'm just putting it out there. Thank you. Please send me 10% check to my office.4 (23m 32s):Yeah, thanks. No, it really, it was one of those things that I, I had a very dear professor at Florida School of the the Arts, Patricia Kadi, she was the acting instructor there and I was doing all of the plays, I was in all of the productions there and I had kind of become the top dog in the school, so to speak. And she pulled me aside one day and she said, you know, the one thing you're gonna have to realize is you're probably not gonna start working professionally until you're in your thirties.4 (24m 13s):And I, and I didn't really understand what she was saying there. What she was basically commenting on was that I was a young character actor and I didn't look like Jason Priestly, I didn't look and yet I hadn't grown into my framer look either. So I was gonna be in this really sort of, where do we cast him? He's talented but we don't know where to put him. And so I did a lot of theater for a lot of years and then in my thirties is when I was able to transfer into television and film. So what, cause I finally had kind of caught up to my look.1 (24m 45s):Yeah. So what I appreciative aid about that is it sounds like she said it so she said it in a way that wasn't like being a jerk, right? Like my experience was feeling that way except having it told like there is something deficient in you so that you cannot be an ingenue cuz you're too fat, you're too this. So instead of, hey, go do some theater, do all the things and then you'll grow into your look, do not fret. This is like part of the technical side of the business of how a camera sees you and not about your talent. It would've been so much different. Instead it comes down to, I think a lot of people we've talked to from the DePauls, from the Northwestern say, nobody told me that in a way which was, I could make a plan about it.1 (25m 35s):It was always just, well you're never gonna be cast. So by, and instead of hey maybe you could do theater, maybe you could write, maybe you could do something else until Hollywood catches up to the character of you.4 (25m 50s):Exactly.1 (25m 51s):It good, Patricia. Good. Is Patricia still around?4 (25m 54s):She is. And she literally just announced today that she's retiring from teaching. Well1 (25m 60s):Patricia, you did good work and you she did fantastic. You made it so call in part of it sounds like she encouraged you cuz you started with that story of her encouraged you to know that maybe later it would be your time to be on every single television show ever written. But for the twenties and the, you know, you were gonna do some theater and, and get your training right man, and,4 (26m 23s):And I honestly, I didn't completely understand everything she was saying in that little sound bite because, you know, I was, I was sort of standing there saying, Patty, look at all these job offers. I just got out of CTCs, you know, I'm gonna be working like crazy. And she said, No, no, no, don't get me wrong that the work is going to be there. But as far as what you're seeing in your mind's eye of, you know, Helen Douglas tonight on The Tonight Show, that's not gonna happen until you can kind of get into that other stream as it were. How3 (27m 0s):So did that match up? I mean, was that a surprise to you or did that match up with what you already thought about yourself? I don't think any 17 year old, 18 year old necessarily thinks of themselves as a character actor. Although it may just be because it never gets put to you that that's an option when you're a teenager. You know, the option is like, as Bos mentioned, Ingenu or not Ingenu, but they never really say like, Well, but you, you know, you're gonna fit into this different mold. So how did that butt up against what you already thought about yourself?4 (27m 32s):It actually kind of lined up okay with me in, in a weird way because at Florida School, the arts in particular, they were so gracious in the fact that when they picked their seasons, they picked shows that it made sense for me to be the lead in, in that I, I'm giving you an example, we did a production of Our Town and I was the stage manager and, you know, as opposed to being cast as the one of the young, you know, lead ingenue kind of a things. And then we did Bye by Birdie and I was cast in the Dick Van Dyke role.4 (28m 12s):And so they did it in such a way that, you know, or when we did Barefoot in the Park, I was Victor Velasco the old man who lived upstairs. So I was already sort of being primed that I was this character actor and would be gonna be doing that kind of stuff. And then quite honestly, as that look started to emerge, I mean in college I had sort of a flock of seagulls kind of hairdo thing going on, you know, and then it quickly all went away. And I had been playing about 20 years older in film and television and in theater than I've actually always been, you know, I was playing guys in my, when I was in my, you know, thirties, I was playing guys in my fifties.4 (28m 59s):Now I'm in my fifties and I'm playing guys in my in1 (29m 1s):In seventies. And I think that calling, the thing that I'm noticing too is like maybe for men it's a little different too, right? Like there's something about being, like, there's just, and it's a societal thing where like women who are play, like, it's, it's a insult for women when they're like, Oh, we're sending you in for a 50 year old and you're 30. But, and I think maybe if you have a certain kind of ego for a man as well, and we all have egos, I mean, it says, but, and I, I love the fact that you didn't, it doesn't sound like anyway, and you can tell me if I'm wrong, you took it as an insult that they were, that you were going out for roles that were for like the Victor Velasco of the world. You were able to embrace it as you were working.1 (29m 43s):Like that's, so I say this all to say, because I remember in our last class with Jim Ooff, who people call hostile prof and he said to me, You know who you are. And I was like, dying to hear you are Michelle Pfeiffer. That was never gonna happen. But I was dying to hear, he was like, That's who you, he's like, you are the next. And I'm waiting and, and I'm waiting. He goes, Lenny Bruce. And I was like, what the actual fuck is going on? What are you telling me?3 (30m 13s):No idea. What a great compliment that was.1 (30m 15s):I was devastated, devastated. I wanted to quit. I was suicide. Like it was just, But anyway, so what I'm saying is you didn't take that and run with it in a way that was like, I am not Jason Priestly and therefore my life is over. You were able to work and, and embrace the roles. It sounds like4 (30m 34s):I was able to embrace the roles and, and I was getting, okay, you are a young dick fan dyke, you're a young, this kind of a guy. So I was able to kind of make that connection. I honestly were being completely honest here. I think, how do I put this, that it does not sound completely like an asshole. It1 (30m 54s):Doesn't matter. We always sound like assholes here. Go ahead.4 (30m 57s):But at Florida school, the arts, I was one of, I was one of the only straight men at school and therefore undated a lot. So I was not, the fact that I wasn't looking like the young hot stud,1 (31m 22s):You were still getting it4 (31m 23s):Right? I was still getting it. So that didn't it, had it not been like that situation, I think I probably would've started to hyperventilate thinking, well hold it, I'm in my twenties, why are they making me play these old men? And this is affecting, you know, cus group. But that wasn't the case. And so I, I had sort of a, a false sense of ego I guess a little bit. But it was supporting the work that I was doing.3 (31m 50s):Yeah, absolutely. So did you grow up always knowing that you wanted to be an actor? Did you think, did you try any other paths first? Or were you, were you dead set on this?4 (32m 2s):I was dead set when the story goes, that when I was four I asked Santa for a tuxedo to wear to the Emmys and Santa delivered gave me a, a white dinner jacket and spats and stuff like that. So I was, I was ready to go.1 (32m 18s):Oh my god, do you have that picture? Can you please send us that?4 (32m 22s):Oh no, we have moved so many times. When I was growing up, my dad, when I was growing up was an undercover investigative reporter. And so wherever he was basically undercover was where we were living. Wait1 (32m 36s):A minute, wait a minute. Wait a minute, wait. Okay. This is fantastic because I do a lot of crime writing and so does Gina writes and undercover crime reporter father now, right there is sort of burying the lead. What in the hell? He was an undercover, What does that even mean? An undercover, He's not a police officer, but he's an undercover reporter.4 (32m 57s):He was an undercover investigative reporter. Well, what that for a period of time, So I'll give you an ex, there was a senator at one time back in the early seventies who was receiving kickbacks from his employees or hiring people on the books. And those people weren't actually having jobs. And so they would then send him the money. He was getting all of the money.1 (33m 24s):Sure. Like Chicago was like living in Chicago all time.4 (33m 28s):So the, somebody tipped my father off that this was happening. And so he went undercover and, and worked as sort of like an aid and things like that. Or there was a time where he, he worked at a meat packing place or he worked at a funeral parlor that was selling caskets with fake bottoms. And so people would buy these incredibly expensive things and then they would drop them and then they'd open up the hatch and the body would just drop into a pine box and then they would reuse the, the casket.1 (34m 8s):So this is the single greatest thing I've ever heard in my life, and I'm gonna write a pilot about it immediately called Fake Bottom. And it's4 (34m 14s):Gonna see, I've already wrote that was, I actually wrote a spec pilot. That's how I landed my lid agent. Oh, it was because what ended up happening is my dad, much to my mom's chagrin, used me in two of his undercover stings when I was a kid. One time, there was a situation where firemen had been hired and they weren't actually properly trained. It was another one of those kind of kickback situations. So it was a training session and they, I was supposedly, it was a staged event where they were gonna try to test the skills of the firemen or whatever.4 (34m 55s):And so I was gonna, I I practiced with a real fireman being fireman carried up and down a ladder from a second story kind of a thing. But once the word was out that it was an internal sting, they put me into one of those crane baskets. And so I was sort of floating over midtown in, in the basket kind of a thing. And then another time actually, there was a talent agent who was running a kitty porn ring. And so I was sort of used to expose, so to speak, this this person that was actually trying to take advantage of, of kids and parents.3 (35m 38s):Oh my God. Well, two things occur to me about that. One is your family was already full of drama before you came along. I mean, anybody who wants to, right, who wants to do this investigative journalism, Like that's, that's a dramatic person. I love David Carr. I love that kind of personality of per, you know, the person who wants to like really get in there, investigate and just as an aside, like, I'm sorry for the families who paid for those coffins, but at the same time, you know, good, good on them because it's such a waste. So much, many people spent putting mahogany boxes into the ground to to, to, to decompose over time. Okay. So did your parents like that you wanted to be an actor or did they have a different idea for plan for you?4 (36m 19s):Oh, they, they were 100% supportive. The very, very much so from day one, I think, because it was my mom who really sort of stepped in and said, Hey, let's figure out how we can get this new kid who's always the new kid to find his people. And so she took me when I was 11 years old to a local community theater, children's community theater. And they were doing a production, a musical version of The Hobbit. And you know, the intention was that I was just gonna audition and be, you know, number 40 in the background kind of a thing.4 (37m 0s):Third,3 (37m 1s):Third habit from the left,4 (37m 3s):Third habit from the, And so they auditioned and I remember you had to sing a song and God, I have not told this story, you had to sing a song. And I decided to sing tomorrow from Annie because I was me madly, deeply in love with Andrea Ricardo. And we were actually pen pals. And so I went in there and I sang tomorrow and jump cut to that weekend. And my mom came in Saturday morning smiling as I was watching cartoons and she said, You've been cast in the lead as Bill Bos. And that was sort of like, okay, I I I found my people.3 (37m 47s):That's amazing. Please tell us more about your penal with,4 (37m 54s):So I, I just, I, you know, I I had gotten the album when it came out and I listened to it and I memorized it. And even then I was casting myself as either Rooster or Daddy Warbuck, you know. And so somehow I found her address and sent her, you know, a, a letter as we used to write, you know, before texting. And she wrote back and then I wrote back, and then the thing that was really exciting was 20,3 (38m 28s):Wait a minute, are you married to Annie?4 (38m 31s):No, I am not married to Annie. Okay. But 20 some odd years later I was doing a national tour and staying in a hotel in Hershey, Pennsylvania. Andrea was on tour doing a national tour and was staying in the same hotel, kind of bumped into one another and was like, you know, you don't know who I am, but this. And it ended up, it was wonderful because I went to see her show on my dark night and she and her family came to see me on, on the other night. So.1 (39m 7s):Beautiful. Okay, so here we go. Your family's on board and why didn't you just go and strike it out either in New York or anywhere? Why did you end up going to school? Were you like, I wanna learn more, or how did that transition into schooling go?4 (39m 24s):It did, I did wanna learn more. It, it really was because up at that point, the only influences as far as acting I was going was from, you know, the, either the community theater directors or the high school drama teacher who had, you know, aspirations for theater, but was really just doing it because he didn't wanna coach the football team. So I felt like I needed a stronger foundation for myself. And, but always it was sort of like I was going to the theater school because I didn't feel like, Oh, I don't wanna go to a school where I'm gonna have to learn all of these other things that I'm not gonna ever use.4 (40m 7s):Now I look back and go, you know, I wish I had done some of that other stuff because I did not create any kind of a fallback plan for me. It would, this is either gonna work or it's not gonna work and you're gonna be screwed. I1 (40m 21s):Mean, here's the thing, here's the thing. I don't know what you, you two think, but like, there is this two schools of, well there's probably a bajillion schools of thought, but one of them is like, if you have a fallback plan, you will fall back. The other one is not everyone is gonna be a Colin Douglas or a John C. Riley that's gonna work, work, work, work, work, work, work. So a fallback plan for some of us might have been like another avenue to get into the industry, right? But a fallback plan can also literally have people go and not live their dreams and become, you know, actuary scientists because they're afraid. So it's like, it's so individual, which is why I think theater school training is so tricky is because you're taking young individuals who don't know shit and some know what they wanna do, some don't, some are good, some are talented, but not, it's so individual.1 (41m 10s):So it's like when people ask me, should I go to theater school? I'm like, I fucking don't know who, I'm like, who are you and what do you wanna do on the planet? But nobody ever asked me that as a 17 year old. So here we are. Gina, you were gonna say something? Oh,3 (41m 23s):I was just going, if you remember your audition,4 (41m 30s):My audition into theater school. Okay. So I do, I remember my audition into anda a, and again, I already recognizing I was a character actor. I sang if I were a rich man from Fiddler on the Roof, you know, you know, a skinny ass, you know, kid from, you know, suburbia singing that song. And then I did a monologue from a play that I had done in high school. And which1 (42m 9s):One do you remember? Or No,4 (42m 10s):It's okay. It was it, yes. No, actually it was weird because I look back on it now kind of thinking how the soul sometimes prepares. I think sometimes it was a, from a show called Juvie, and I played a young gentleman who was mentally challenged and I got a lot of incredible feedback from, from the role because I had researched, I had, I had gone to the library and this is, there was a thing called Microfish when you would go to the library and you'd have to look up stories on kind of like a big machine. And I did all of these kind of things and research the roles, and I saw images of babies and young people with different kind of cognitive delays.4 (42m 60s):And so I did that. I got into Amda, whatever, again, sort of jumping forward in life. In 1996, my oldest son was born and he happened to be born with Down syndrome. And when I met him for the first time at the bassinet, I immediately went back to that Microfish machine in high school and remembered seeing babies and images of people with Down syndrome. And so I made that kind of connection. So it was sort of like, all right, this is where life was going as far as Florida School, the arts went, I actually didn't audition for that.4 (43m 43s):What had happened is I was at, and I broke my foot during one of the dance classes. They would bring in dance captains from various Broadway shows and teachers routines. And we were doing a routine from cats and I jumped off of a piling and I came down flat for,1 (44m 5s):Let me tell you something. This is what, this is just one of the many reasons I don't care for that musical is that also what are you having people jumping around for that? Aren't I just, anyway, I'm glad they brought, I'm sure it was a great experience in some ways, but like, I just don't care for, that was my first musical I saw. And I even as a kid, I was like, I don't buy this at all. I don't know what's going on here, but I don't like it. But anyway, so you busted your foot. Oh, and can I just say about microfiche? I'm sorry to be an asshole, but like, I could never figure out how to slow the fucking shit down and I never could see a goddamn story, so I gave up on the microphone, so you made it further than me. I was like, why is it going too fast? That was my, that's like, like, that's like so indicative of my life. But anyway, so okay, so you, you broke your foot and so what happened?1 (44m 49s):You had to, why did you4 (44m 50s):So I, I, I broke my foot, I went home to my parents' place who were now living in Florida and kind of rehabbed for a while. I then auditioned for a play for Pirates of Penza, excuse me, that was up, up performances up near St. Augustine, Florida. And I went up there and I was playing Samuel the the second pirate. And the gentleman who was playing the modern major general in the show was actually the dean and artistic director of Florida School of the Arts. And he said to me, If you'd like to come to school, we'll offer you a full scholarship and you can start at the, as soon as the show closes.4 (45m 38s):And so that's what I did. It was like, I just went straight to Flos Bureau Arts and I did not go back up to Amda after my footed here. Helen,1 (45m 45s):It's really interesting, like, and I was talking about, this was someone else yesterday about how one, obviously one thing leads to the next, Oh it was a showrunner actually, that was that I was listening to a lecture and she just said that what I've done is I have walked through doors that have opened to me without a lot of second guessing. I followed my heart in terms of who took interest in me and who opened doors for me. I walked through them. I didn't say no, but, or no, I just did it. And so it sounds like that's what you did. You were like, Oh, full ride, I'm in Florida now. You could have been like, No, no, no, I'm gonna go back to Amda because whatever.1 (46m 26s):But you were like, I'm gonna do this. And it sounds like it worked in your favor, but what was your experience like at Florida? Did you, I mean obviously we know you left early, but did you get stuff out of it? Did you love it? What was the deal?4 (46m 41s):I did love it in the sense that because it was such a small school and because where the school is located, it's in Plac of Florida, which is sort of geographically in the middle of sort of Jacksonville and Gainesville. And so on a Friday night there really wasn't any partying going on. It was all of us getting together and doing monologues for one another, you know, because there wasn't any place to really go. And then as far as the classes went, because it was such a small institution, so many of my classes were literally just myself and professor in their office.4 (47m 26s):And we would do, you know, that's how I learned dialects was literally just, you know, we were working on the Italian dialect or whatever and I would go in and the professor would speak to me in that Italian dialect and then I would have to answer him and that would be the entire class. And then the next week we would do the brooklynese. And so I had all of that and they were very, very gracious to me because when I came in as quote a freshman, I was taking all of the freshman courses, but then they also had me taking all of the second year acting courses as well, sort of accelerating me through the program and then allowing that by doing that I was able to be cast in all of their different productions.3 (48m 15s):So when you did school and enter the workforce, what surprised about sort of the business that maybe you weren't expecting or hadn't been prepared for? For in terms of your training or, you know, and it could have been a happy surprise or, or, or not such a happy surprise, but like what was some I always just feel like there's, people have their list of things. Oh, I never thought the one that people always bring up as coverage, I never thought, when I watched TV shows that they had to do the same thing 50 times.4 (48m 58s):I, I think for, for me, the biggest sort of, even though Patty Crotty, Patricia Crotty had said, you know, Hey, it's gonna be a while before you're gonna start to work. You know, although I did work immediately when I got outta school, it was, it was one of those things where I quickly realized that they really didn't care that I had played Albert and by by Birdie they didn't care that I was in all of the productions. It was basically, no, you've earned the right to stand in the back of a line and you're gonna have to, you know, get up at an ungodly hour, go to equity, sign in at 6:00 AM and then come back at two in the afternoon for your audition.4 (49m 47s):But by the time you come back, if you pick up backstage, you're gonna read that Robert Strong Leonard has already been offered the role that you're auditioning for at two o'clock. So those were sort of some of the realities of, oh, okay, this is not necessarily gonna be the projecting thing that's gonna get me into the room. It's just, it's gonna be more for me that, okay, I feel like I deserve to be here and I'm competent enough in my abilities. But I, I think that was as far as just working in general. But Gina, to answer the question as far as like the thing that I was most surprised by within the industry, I'm, I'm trying to think if there was anything that I really was sort of taken aback by,1 (50m 31s):Well I guess I can ask like, did you, what was your like, like in terms of getting an agent and all that, did anything there go like, Oh my gosh, I didn't understand that I would have to, How did your representation come about? Was that a surprise or did you just get an agent? Cause a lot of our listeners, some of them we talk, you know, we talk about like a showcase or, but you left early and just started working, so what was that transition like in terms of getting representation and going on, on auditions for film and TV or theater? And if you think of anything that surprises you along the way, just let us know. But sure,4 (51m 4s):I didn't have theatrical, I didn't have legit theater representation for a lot of years. I was literally very lucky in that, you know, just using relationships, you know, to help propel me into the next situation that one show would be closing and I would hear about the fact that they were looking for something else. Or I would go to the Southeastern Theater conference and audition and be able to pick up my next year or year and a half worth of work. And I was able to kind of keep it at that point. I finally did get an agent who was gonna cover me theatrically as well as, you know, commercially.4 (51m 46s):And I remember her telling me, she was basically saying the same thing that Patty Crotty had said is that, you know, you know, you're a good actor, I'll put you out there, but it's, it's probably gonna be a while before you're gonna book a commercial or any kind of television cuz you're just really hard to place. She was good to her words. She put me out there and a week later I booked a Budweiser commercial. So I was like, Oh, okay, I think I got this. I, I think the hardest lesson that I had to learn was that because it sometimes came easy, it felt like, like, oh, okay, this is what it was, is I would get say to that chunk of change.4 (52m 29s):And I, it took me a while to figure out that I had to make that chunk of change, stretch as far as I possibly could because I didn't know exactly when the next job was coming from and, and that it was hard when I met and fell in love with my wife who was coming. She had been a model, but she had also worked in the corporate world. And so she was very accustomed to, well no, you make this amount of money every month and this is what you can expect with your expenses. It was hard when we started to realize, oh no, CU just got a great windfall of money, but if you break it down and spread it out over a year, he's not making minimum wage.4 (53m 10s):So, you know, it was a really, that was a hard kind of thing to adjust with.3 (53m 15s):Yes. I mean that's, yes, that's a common story and that's something that they don't teach you about in theater school. They don't teach you money management and how you have to withhold taxes and all kinda stuff. Yeah. So that, that's that, that's, that's a whole education in and of itself. But you were also a writer and director. When did the writing and directing and producing come into your career?4 (53m 40s):The writing actually started in college in that we would have to have monologues for class and I had an affinity to writing the monologues and so I started writing monologues for my classmates for beer money or they would need an audition piece for something in particular. And so I would tailor it to sort of echo whatever play that they were auditioning for kind of a thing. And so it really just sort of came easy for me. And then whenever I was auditioning, my biggest thing was I don't wanna go in there with something that they have seen 3000 times.4 (54m 23s):And so I was like, Okay, you know what? I'm just gonna write my own thing. And it worked, it worked to a degree. And so that's where I sort of started to do it. And then personally after my oldest son Gabe was born, I had a lot of demons to be dealing with. I didn't understand why I had been chosen or whatever, or, or given a child with a disability and, and it took me kind of having to get outta my own way to realize that was the least interesting thing about him. And, but in doing so, I, I started to write in journals and then I ended up writing a one man play that I in turn tour the country with for a handful of years.4 (55m 11s):And it was that play that I then attracted some other attention and then got hired on to do some other writing in script doctoring or whatever. And then as I shared earlier, I wrote a spec script about that time of my life when we were kind of moving into hotels and things like that. And then that kind of just started to snowball. And then I was very fortunate back in 2010, I had the Humanitas Organization, Humanitas Prize. They tapped me as the first recipient of their New Voices fellowship program, which pairs you with showrunners to sort of mentor you in creating a television series.4 (56m 0s):And so I was shared with, paired with Shonda rhymes over at Shondaland and was able to develop a show, which was actually an adaptation of my one man play, about a family, you know, coming to terms and dealing with a child with a disability. But I had already actually had a relationship with Shawnda prior to that because I had gotten cast in an episode of Grey's Anatomy and she and her producing partner, Betsy Beers, put me up for an Emmy for that role. And then when I didn't get the nomination, Shawnda turned around and created a role for me over on private practice.1 (56m 46s):Okay. So you know, all these people, and I guess I'm mindful of time and I wanna know what the hell are you, are you doing now you have this documentary, What is your jam right this second? Colin Douglas. And if you could do anything, what would it be? And tell us about this documentary, because what I don't wanna happen is it's like 10 minutes go by and we haven't heard about the documentary and we haven't heard about like, what is your jam and your juice right this second.4 (57m 13s):Okay. So I, I made the documentary, I started working on it when we got locked out, you know, the world was hurting, the industry was shut down. I couldn't stand in front of a camera, I couldn't direct a bunch of actors in a narrative, but I knew I could still tell stories. And so I, at one point in my career, I detoured and I was an associate show director and a performer at Walt Disney World. I was there for about three years. And the level of talent in those theme parks is just incredible. You know, there are a lot of people who come outta theater schools and they get their job, you know, at Dollywood or at Bush Gardens or at Disney World or Disneyland, and they spend the summer there and then they go off and do whatever else with their life.4 (58m 5s):There are other individuals like the subject of my film, Billy Flanigan, who, he started right after theater school. He went to Boston Conservatory. He then opened up Epcot in 1982 as a kid at the Kingdom and has been working for 40 years straight as a performer out at Disney. When the Disney Park shut down because of the pandemic, Billy was without a stage for the first time in his 40 year career. So what he did is he took it upon himself to start doing singing and dancing telegrams for other performers who were out of work. And then he started to literally take it on the road because he's a cyclist and he started crisscrossing the entire country, delivering these sing in dancing telegrams called Planograms.4 (58m 55s):And my Facebook page was blowing up with, I got Planogrammed, I got Planogrammed and I, so I reached out to some old friends from Disney and I said, I've heard about this name Billy Flanigan for years. He's a, he's a legend. He was a legend 20 years ago when I was working, You know, can you put me in touch with him? And so I spoke with Billy. I reached out to my producing partner and I said, There's a documentary here, because Billy has just been so incredibly selfless. He's always a pay it forward kind of a guy. He's a performers performer, you know, even though he jokes about the fact that he'll get a nosebleed if he's not on center.4 (59m 36s):But it's one of those things where he just really is about making the other people on stage look good. So he's been the face of Disney. But then what ended up happening is he was so busy working and raising an entire family that a handful of years ago, Billy finally slowed down and realized that he had been living a different life than he perhaps should have been. And he came out and it really destroyed his family and, and brought things down. And so you had this guy who day in and day out was still having to give that Disney, you know, RAAs, but behind the scenes, as we all know, his performers, the show's gotta go on.4 (1h 0m 20s):And so his heart was breaking. And so I said to Billy, Look, if we tell your story, we're gonna have to tell all of it, because I feel like you sharing your humanity and your pain is gonna help other people out there within the L G B T community who are feeling bullied or feeling like they don't have their place. So if we can do this, this is, this is sort of our mandate. And he said yes. And his family said yes. And, and thankfully not as a direct link to the film, but I shared the final cut with Billy and his family, because obviously I had to have their final approval. And Billy called me and said, This film is helping heal my family now, because it had given them that creative distance that it was no longer them, it was these other people up on a screen talking about a period of their life.4 (1h 1m 13s):So right now, the film, it premieres digitally on October 7th, and then is available on D V D November 15th. And then after the first of the year, it'll be looking like landing on one of the major streamers.3 (1h 1m 29s):Oh, that's fantastic. I'm so excited to see it because I watched the trailer and that thing that you were describing about, you know, he's, he's, he's gotta always have a stage that comes through from the first frame. You see him, you think, Wow, this guy is like a consummate performer in a way that I could never imagine. I mean, yes, I, I love to be on stage. It's fantastic, but I, I don't have this thing where like, you know, I've gotta be performing every second. And that was really clear. And I didn't know, I didn't glean from the trailer that he was doing that for fun for other performers. I thought he was just starting his business with the singing telegram. So that is even more interesting. Okay, that's really cool.3 (1h 2m 9s):So after the first of the year, it'll come out on a streamer. And actually when you know which one it is, you'll let us know and we'll, we'll promote it on our socials. And I4 (1h 2m 17s):Wanted, but you can preorder now the DVD and the digital.1 (1h 2m 22s):Yeah. I didn't mean to like cut us off from Shonda land, but I really wanted to make sure that we talk about this documentary because I think that it is taking your career and your life in, it's like it's made it bigger and about other things other than, I mean, it's like there's a service component to documentary work that like, I think is not always there in other kinds of media. That documentary work is like at once, for me anyway, really personal, but also universal and also has a great capacity for healing. And so, or at least the truth, right? Like what is the truth?1 (1h 3m 2s):So that's why I wanted to make sure we covered that. But if there's other things you wanna say about your career and like what you're doing now and where you wanna go or anything else, I wanna give you the opportunity, but I wanted to make sure, So I didn't mean to cut off your Shonda land story because I know people are probably like, Oh my God, tell more about Sean Rhymes. But I wanted to talk about the, the Billy documentary.4 (1h 3m 24s):I appreciate that so much. No, I, I, you know, just to sort of bookend the, the documentary, I never felt like it was one of those things that I knew I could tell stories, but I didn't feel like I had any business telling the documentary. I don't necessarily even gravitate towards documentaries, but I just felt like, hold it. This truly is a story that that needs to be told and can maybe bring about a little bit of healing. And that's what I think good films and television do that you, we, we see ourselves mirrored back in many ways and we feel less alone.4 (1h 4m 5s):And so I felt like if I could do that with a narrative, maybe I can do it with a, a documentary. That's not to say that I wanna become a documentarian, because it's not that I wouldn't if the opportunity ever presented itself, but it's the same way in which, you know, writing a narrative feature, it's like, well, I've gotta be compelled to wanna tell this story kind of a thing. And this just happened to be the medium in which to tell it as opposed to making a, you know, a, a film about a guy named Billy who wants to start out being a performer.1 (1h 4m 40s):And I think that you've said a really good word that we talk about sometimes in other ways on this show and in my life I talk about is being compelled. So when someone is compelled to do something, I know that the art created from that feeling of being compelled is usually authentic, true necessary, and, and, and, and, and sometimes healing. So I love the word what doing projects that were compelled. So anything else that you're compelled to do right now?4 (1h 5m 14s):Work great, really, you know, I I, I really, I I still even after, you know, making this, this film, I, I am still very much an actor at heart and I love being on camera. I love the collaborative experience working with other actors. You know, I was very, very fortunate this past season to to work on Barry with Bill Hater and Bill, I guess if I, it was like, what's next? What's my next jam? I would love to be able to emulate what Bill is doing. You know, Bill is the lead. He's also writing, he's also directing all of the episodes.4 (1h 5m 58s):You know, I joked with him that he also ran craft services because it was literally doing all those things and just watching him effortlessly move from being Barry back to Bill, giving me a note and then giving a note to the DP and then stepping back into Barry was just a really wonderful thing. And it's like, you know what, if I can do that, and I have other friends and, and mentors like Tom Verica, Tom actually directed me in that first episode of Grey's Anatomy. And he and I have since become dear friends. He's now the executive producer and resident director on Bridger.4 (1h 6m 39s):He also was the resident director and producer on inventing Anna. And he and I have developed a narrative film that we're looking to produce as well. And, and, and so again, and yet, you know, Tom as sort of an aspiration or an inspiration for me. And he started out as an actor himself. And then, you know, he directed a lot of Grey's Anatomy and then the next thing you know, he's playing Vila, Viola Davis' husband on how to Get Away with Murder. And then he was also the lead producer on Scandal. So it's like, you know, not being defined by what this industry wants to put you in.4 (1h 7m 20s):I feel like I'm finally at the point in my career where Colin can direct a documentary and he could write something for somebody else and he could act. And, and again, you know, from day one when I, when I left Flow Arts early to go out and do the job, it's just because I wanna keep working. Yeah.3 (1h 7m 38s):And that's, that's, everybody says that. Everybody says, I just wish I could be working constantly. Cuz it's where it's where all the fun of, of the work is, you know, not auditioning and getting head shots and whatever. It's, it's, it's doing the work. By the way, Barry is how I came to ask you to be on this podcast, because I didn't watch it when it first came out. I, I kind of came to it late and of course binge the whole thing and it's fantastic. And, and I immediately went and looked up every single actor to see who went to theater school because I, I would love to have them all. What a fantastic show and what an interesting kind of nice little parallel somehow with your documentary and, and also your own story.3 (1h 8m 18s):There's a lot about actors like figuring out what they're doing on screen and, and kind of reconciling that with their offscreen life or, or even just with their career. Do I wanna be this type of actor? Do I wanna be this type of person? You know, Ha and Bill Hater has seamlessly gone, I mean, once upon a time you would not have really thought of a Saturday Night Live person making quite this kind of crossover. And the humor in that show about actors is so perfect. I've ne I've seen things that have come close to that, but I've never seen something that you're just dying laughing if you know anything about the acting profession, Right?3 (1h 8m 58s):Yeah. Or were you gonna say that?1 (1h 8m 59s):I was gonna say that. And also that like, his account, So I have suffered, you know, from panic attacks and anxiety disorder and his journey through that and with that has given me so much hope as a artist because he was one of the first people I knew, especially from snl, especially from comedy, to say, I was struggling with this and this is how I dealt with it. So it didn't totally destroy my life. And he could have chosen to be like, I'm having panic attacks on set at Saturday Live. I'm done, I'm done. But he worked through it and now is doing all of this. So it gives me a lot of hope. So if you talk to him, tell him there's a late, an anxious lady that really feels like I can, I can really reclaim myself as an artist and even maybe thrive through the anxiety.4 (1h 9m 50s):No, I, I, I so appreciate that, Jen. I really do. You know, I have dealt with panic attacks over the years, you know, again, being that new kid, I was kind of predisposed to, Oh my gosh, you know, and luckily I've never had it within my art. It's always been on the other side. But the way in which Bill has navigated all of that is really truly just, you know, motivating and inspiring on so many different levels. And I think the thing that I also recognize is the fact that Bill never had aspirations to be on snl. He wanted to be a filmmaker, you know, he was editing, he was doing all these types of things and he sort of fell in backwards to groundings and, and all that kind of stuff.4 (1h 10m 38s):And somebody saw him and said, Hey, let's do it. It's sort of like he had to kind of take that detour to be able to get back to doing the kind of things that he really wanted to be doing, you know, Which is great for me because I look at like, my time at Disney, okay? I never would've imagined that that brief time at Disney would've been able to fuel me in that it brought back into my life to allow me to direct a film about one of their performers 20 years later.1 (1h 11m 6s):It's a, your story. I'm so glad you came on because your story is a story about the, the consistent inconsistencies and the detours that aren't really detours. And for me, like just being like, I'm just knowing now going into into meetings, being a former therapist for felons. Like that is the thing that people are really interested in. And I
We're back. And the wonderful and funny Abby Wambaugh is joining us! This week, we talk staying warm in cold water, Abbys war on the rejsekort and the last Queen of Europe (second last at the time of recording!) We also talk to Alun Thomas, writer of CTCs newest production. Hosted on Acast. See acast.com/privacy for more information.
We're back. And the wonderful and funny Abby Wambaugh is joining us! This week, we talk staying warm in cold water, Abbys war on the rejsekort and the last Queen of Europe (second last at the time of recording!) We also talk to Alun Thomas, writer of CTCs newest production.
We're back. And the wonderful and funny Abby Wambaugh is joining us! This week, we talk staying warm in cold water, Abbys war on the rejsekort and the last Queen of Europe (second last at the time of recording!) We also talk to Alun Thomas, writer of CTCs newest production. https://www.instagram.com/the_cic_show/?hl=en
An interview with Dr. Lynn Henry from the University of Michigan in Ann Arbor, MI, lead author on "Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update." Dr. Henry reviews new biomarkers for the purposes of making treatment decisions for triple-negative breast cancer, and hormone receptor-positive, HER2-negative breast cancer, as well as tumor agnostic tumor biomarkers. Specific biomarkers addressed in this conversation include PIK3CA, ESR1, BRCA 1/2, PALB2, HRD, PD-L1, dMMR/MSI-H, TMB, NTRK, ctDNA, and CTCs. Read the full guideline at www.asco.org/breast-cancer-guidelines. TRANSCRIPT Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs, covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one at asco.org/podcasts. My name is Brittany Harvey and today I'm interviewing Dr. Lynn Henry from the University of Michigan in Ann Arbor, Michigan, lead author on 'Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update'. Thank you for being here, Dr. Henry. Dr. Lynn Henry: Thank you very much for inviting me to participate. Brittany Harvey: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Henry, do you have any relevant disclosures that are related to this guideline topic? Dr. Lynn Henry: No, I do not. Brittany Harvey: Great! Thank you. Then let's talk about the scope of this guideline. So, what prompted this update to the guideline on the use of biomarkers to guide decisions on systemic therapy for patients with metastatic breast cancer, which was last updated in 2015? And what is the scope of this guideline update? Dr. Lynn Henry: Yes, so a lot has happened in the past six or seven years that influence how we treat metastatic breast cancer. And there are many new drugs that have been approved by the FDA during that time. When we reviewed the prior guideline and the new treatment landscape, we realized that while much of what was included in the old guideline was still relevant, there were quite a number of new biomarkers related to new drugs that needed to be included. The newly recommended biomarkers are primarily applicable to making decisions about treatment of estrogen receptor, progesterone receptor, and HER2-negative breast cancer, also called triple-negative breast cancer, as well as for treatment of hormone receptor-positive HER2-negative breast cancer. And finally, there are now some tumor biomarkers that can be tested for that are tumor agnostic, and these were included as well. Brittany Harvey: Great! So, then let's discuss the updated guideline recommendations based off these new biomarkers for our listeners. The guideline reviews testing for several different biomarkers. So, I would like to review each of the biomarkers that the panel assessed. Let's start with what is the role of PIK3CA mutation testing? Dr. Lynn Henry: Yeah! So, PIK3CA activating mutations are commonly found in tumors that are hormone receptor-positive and HER2-negative. Based on the results of the SOLAR-1 trial, patients whose tumors have an activating PIK3CA mutation had improved progression-free survival when treated with the PI3 kinase inhibitor alpelisib plus fulvestrant compared to fulvestrant alone. This improvement was not seen in patients whose cancers didn't have a mutation. So, therefore, this provided the evidence for the clinical utility of evaluating tumors for the somatic PIK3CA mutations. Testing of either a tumor specimen or plasma to look for PIK3CA mutations can be performed. However, it's important that if the plasma is tested, and no PIK3CA mutations are identified in the circulating tumor DNA, then our tumor specimen should really be tested if possible, because of the possibility of a false negative finding in the plasma. Also, since these mutations can be acquired over time, a more recent specimen should be tested if possible, as opposed to testing the primary tumor. Finally, in the SOLAR-1 trial, a patient's tumor had to have one of the 11 pre-specified PIK3CA mutations in exon 7, 9, or 20. And therefore, when mutations are identified using next-generation sequencing, it is important to confirm that the identified mutation is one of those 11 activating mutations and not a different one that may not convey benefit from treatment with a PI3 kinase inhibitor. Brittany Harvey: Great! I appreciate you're reviewing that recommendation, as well as the clinical utility of it and the evidence behind it. So, then following those recommendations, what is the role of testing for ESR1 mutations? Dr. Lynn Henry: At this time, there are insufficient data to support routine testing of metastatic hormone receptor-positive HER2-negative tumors for ESR1 mutations. However, the panel did note that there's a retrospective analysis of two different phases three trials that demonstrated that fulvestrant improved progression-free survival compared to the aromatase inhibitor exemestane in patients who had previously progressed on a non-steroidal AI and whose tumors had an ESR1 mutation. Importantly, there are ongoing clinical trials addressing this issue, including the PADA-1 trial, which is evaluating the effect of the switch of fulvestrant from aromatase inhibitor therapy, versus remaining on that therapy when ESR1 mutations are detected in the blood. However, although preliminary findings were presented at a recent large breast cancer meeting, and were suggestive of a possible progression-free survival benefit from switching therapy, data have not yet been published, and therefore they were not included in this guideline. Brittany Harvey: Great! So, we'll look forward to those updated data to potentially review that recommendation in the future. So, following those recommendations, what is the role of testing for germline BRCA 1 or 2 and PALB2 pathogenic mutations? Dr. Lynn Henry: So, the answer for germline BRCA1 and BRCA2 mutations is relatively straightforward. Patients with metastatic HER2-negative breast cancer can be either hormone receptor-positive or negative, and who are candidates for treatment with a PARP inhibitor should undergo testing for germline BRCA1 and BRCA2 pathogenic or likely pathogenic mutations to determine whether they should receive treatment with a PARP inhibitor. This recommendation is based on the results of two large randomized clinical trials comparing PARP inhibitor therapy to physician's choice chemotherapy, although notably, the chemotherapy options did not include taxanes, anthracyclines, or platinums. In contrast, there remains insufficient evidence to support a recommendation either for or against testing for germline PALB2 pathogenic variant for the purpose of determining eligibility for treatment with a PARP inhibitor. The panel did note, however, that there are small single-arm studies that show that there is high response rate to PARP inhibitors in patients with metastatic breast cancer and coding DNA repair defects, such as either germline PALB2 pathogenic variants or somatic BRCA1 or 2 mutations. It was also noted that it is likely that patients who harbored mutations in these genes will actually be identified through routine testing with panel testing for germline variants. Brittany Harvey: Okay, understood. So, then following those recommendations, what is the role of testing tumors for homologous recombination deficiency? Dr. Lynn Henry: So, although there are emerging data from other solid tumors to support the use of homologous recombination deficiency, or HRD testing to guide therapy, current data do not support the assessment of HRD in the management of metastatic breast cancer. Therefore, we did not recommend routine testing of tumors for HRD at this time. Brittany Harvey: It's important to note where we both have evidence and where we don't have evidence. So, then what is the role of testing for expression of PD-L1 in metastatic breast cancer? Dr. Lynn Henry: So, the panel recommends that patients who are candidates for treatment with immunotherapy, with either a PD1 or PD-L1 inhibitor, should undergo testing for expression of PD-L1 in the tumor and immune cells with an FDA-approved test. At present in the United States, pembrolizumab is the only approved immunotherapy for the treatment of metastatic breast cancer, and it is given in combination with chemotherapy. The FDA-approved test for this drug is the 22C3 assay which evaluates PD-L1 staining in the tumor and surrounding stroma to calculate a combined positive score or CPS, with positive considered to be a score of 10 or greater. Of note, in other countries, there are different anti PD1 and PD-L1 antibodies that are approved for treatment, and each has been approved with its own companion diagnostic. So, it is important to make sure that you're using the right biomarker test, depending on which drug you are planning to use. Brittany Harvey: Great! I appreciate you reviewing the test in addition to the role of the biomarker. So, then, following those recommendations, what is the role of testing for deficient mismatch repair microsatellite instability-high? Dr. Lynn Henry: Similar to PD-L1 testing, it is recommended that patients with metastatic breast cancer who are candidates for a treatment regimen that includes an immune checkpoint inhibitor should undergo testing for deficient mismatch repair or microsatellite instability-high to determine eligibility for treatment with one of the drugs that is currently FDA approved, either dostarlimab or pembrolizumab. In contrast to the PD-L1 data, however, there are no randomized studies that have been conducted specifically in patients with breast cancer addressing this question. The testing recommendation was therefore included in these guidelines because of the tumor agnostic FDA approval of these drugs. In terms of which biomarker methodology to use, it was noted that, while the original studies assessed the deficient mismatch repair and MSI high using immunochemistry, and PCR respectively. The FDA has subsequently approved the next-generation sequencing platform to use in selecting candidates for these treatments. And so, therefore, there are a number of different tests that can be used. Brittany Harvey: Thank you for reviewing those recommendations as well. So, then following, what is the role of testing for tumor mutational burden? Dr. Henry Lynn: So, tumor mutational burden describes the quantity of somatic mutations in the tumor. Similar to the biomarkers we were previously discussing, there are minimal data specifically in metastatic breast cancer to support the assessment of tumor mutational burden for making treatment decisions. However, the testing recommendation was again included in the guidelines because of the tumor agnostic FDA approval of the drug pembrolizumab in the setting of high TMB. And also there is one single arm phase two trial that looked at this specifically. Importantly, the panel noted that there are a variety of factors that influence assessment of TMB. These include sample type, pre-analytical factors so how the sample was handled, the size of the panel and mutations that are tested, depths of the sequencing, type of the mutations that are included on the panel, and cut point variables. So, in particular, assessment of TMB in cell-free DNA assays such as circulating tumor DNA is an area of evolving evidence. There are therefore very important caveats to be aware of when selecting a TMB assay and assessing the results, many of which are outlined in the guideline manuscript itself, and different assays can yield different results for the same tissue specimen. It is therefore very important to use the approved companion assay and the approved cut point when making decisions regarding a specific treatment. Brittany Harvey: Absolutely. I appreciate your reviewing those details. So, then what is the role of testing for neurotrophic tyrosine receptor kinase? Dr. Lynn Henry: So, I'm going to abbreviate that to NTRK. So, NTRK fusions are rare in metastatic breast cancer. One study said 0.39% of all breast cancers have NTRK fusions. So, as with the above biomarkers, the NTRK testing recommendation is based on the results of phase 1 and phase 2 studies that were identified by the panel evaluating the efficacy and safety of these inhibitors for the treatment of advanced solid tumors with NTRK gene fusions, noting that there are only minimal data available that are specific to metastatic breast cancer. Brittany Harvey: Understood. Some of these are very rare in metastatic breast cancer. So, then, following that recommendation, what is the role of using circulating tumor DNA? Dr. Lynn Henry: So, for circulating tumor DNA, although the ctDNA technology holds promise in metastatic disease, for its ability to potentially identify tumor-specific mutations that are shed into the blood and that may be targetable, to date, neither the measurement of changes in ctDNA as a marker of treatment responsiveness nor identification of specific mutations in the blood to direct therapy has actually been prospectively shown to improve patient outcomes compared to standard imaging-based detection of tumor progression. Therefore, at present, the guideline does not recommend routine assessment of ctDNA for monitoring response to therapy among patients with metastatic breast cancer, although many studies are underway evaluating this question. Brittany Harvey: Understood. Then the last biomarker that the panel assessed in this guideline update, what is the role of using circulating tumor cells? Dr. Lynn Henry: Similar to circulating tumor DNA, there are insufficient data to recommend routine use of circulating tumor cells to monitor response to therapy among patients with metastatic breast cancer. To date, studies that have examined the clinical utility of this marker to determine the optimal time for treatment change have not led to improvements in outcomes in metastatic breast cancer. Brittany Harvey: Great! Well, thank you for reviewing all of these recommendations. The panel certainly took on a lot of biomarkers and performed a critical review of all the evidence to make recommendations in this setting. So, in your view, Dr. Henry, what is the importance of this guideline update and what should clinicians know as they implement these updated recommendations? Dr. Lynn Henry: Yeah, that's an excellent question. So, this guideline addresses the key questions that we face, as we're making decisions about how best to treat patients with metastatic breast cancer. Importantly, the guideline highlights the current state of the science, with a focus on the available published data from randomized clinical trials. It also discusses the limitations of our current knowledge, as well as key considerations for different biomarkers. Of course, we recognize that there are new data emerging on a regular basis. And the panel therefore also highlighted where data are anticipated but not yet available, as well as key questions which we hope will be able to be addressed in the more distant future. Brittany Harvey: And then finally, how will these guideline recommendations affect patients with metastatic breast cancer? Dr. Lynn Henry: Yeah, so really, that is the bottom line, isn't it? So, ideally, this guideline will enable the dissemination of best practices in terms of biomarker selection and analysis to guide clinicians as they are making treatment decisions in conjunction with patients. Treatment of metastatic breast cancer has become more complex, with regimen selection affected by both inherited germline genetics and somatic changes in the cancer that can evolve over time. The assessment of relevant biomarkers should allow patients to receive the optimal therapies that are most likely to be effective based on the individual characteristics of their cancers. Brittany Harvey: Well, I want to thank you so much for reviewing this guideline with me today, and all of the recommendations and our gaps in evidence, for our listeners. Thank you for your work on this guideline update and thank you for your time today, Dr. Henry. Dr. Lynn Henry: Thank you so much! Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app available on iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.
Today's guest is Jason Christiansen, Chief Technology Officer at Epic Sciences in San Diego. Founded in 2008, Epic Sciences is developing novel diagnostics to personalize and advance the treatment and management of cancer. Epic's mission is to enable the rapid and non-invasive detection of genetic and molecular changes in cancer throughout a patient's journey. The company was founded on a powerful platform to identify and characterize rare cells, including circulating tumor cells (CTCs). Epic's technology helps match patients to targeted therapies and monitor for drug resistance, so that the best treatment path can be chosen at every clinical decision point. Today, they partner with leading pharmaceutical companies and major cancer centers around the world. Their goal is to commercialize our technology to increase the success rate of cancer drugs in clinical trials and improve patient outcomes by providing physicians with real-time information to guide treatment choices. In the episode, Jason will discuss: The work he is doing with Epic Sciences, Current projects the data science team are working on, Use cases of the impact their products bring to the industry, What the future holds for Epic Sciences & How they attract top talent to join the team
Kenna Anderes Ph.D., RAC, Vice President of Translational Medicine & Companion Diagnostics at Mirati Therapeutics, talks → The art of partnering: How your small company can change the game for big companies; plus, “FIO” Figure it Out, how to follow the data, and navigate complex timelines and more. Dr. Anderes has been a scientific leader in oncology drug discovery, biomarker identification and early clinical development in the pharmaceutical and biotech industries for over 20 years. She is trained as a pharmacologist and cancer biologist and has held a number of senior executive and scientific advisory positions at pharmaceutical, biotech and in vitro diagnostic companies. As an early employee in several startup companies, Dr. Anderes acquired very broad, interdisciplinary technical and business skills, with breadth in science, clinical research, clinical operations, regulatory strategy, product/medical device development. Achievements range from lead identification of novel small molecule or biological entities to characterization of clinical development candidates for several distinct first in class molecular targeted agents to treat cancer. She has extensive experience directing and designing studies to determine relationships to drug exposure, mechanism of action, efficacy and biomarkers in the single agent and combination settings in vitro and in vivo in classical xenografts and patient derived tumor models. In parallel to drug discovery/development activities, Dr. Anderes has led equally diverse biomarker and in vitro diagnostic projects. She has evaluated numerous liquid biopsy approaches and served as an advisor on pharma sponsored clinical trials to evaluate clinical utility of CTCs and ctDNA. Delivery on the promise of personalized medicine requires strategic and tactical translational medicine expertise, Dr. Anderes formed Translational Medicine Partners, Inc. and co-founded Wild Type Advisors, LLC to provide bespoke consulting services for the life sciences, biotechnology and pharmaceutical industries.
Dr. Nerymar Ortiz-Otero from the Meinig School of Biomedical Engineering, Cornell University, discusses a research paper she co-authored that was published by Oncotarget in Volume 11, Issue 12, entitled, “Cancer associated fibroblasts confer shear resistance to circulating tumor cells during prostate cancer metastatic progression.” DOI - https://doi.org/10.18632/oncotarget.27510 Correspondence to - Michael R. King - mike.king@vanderbilt.edu Abstract Previous studies have demonstrated that CTCs do not travel in the bloodstream alone, but rather are accompanied by clusters of stromal cells such as cancer associated fibroblasts (CAFs). Our laboratory has confirmed the presence of CAFs in the peripheral blood of prostate cancer (PC) patients. The observation that CAFs disseminate with CTCs prompts the examination of the role of CAFs in CTC survival under physiological shear stress during the dissemination process using a clinically relevant, three-dimensional (3D) co-culture model. In this study, we found that “reactive CAFs” induce shear resistance to prostate tumor cells via intercellular contact and soluble derived factors. In addition, these reactive CAFs conserve the proliferative capability of tumor cells in the presence of high magnitude fluid shear stress (FSS). This reactive CAF phenotype emerges from normal fibroblasts (NF), which take on the CAF phenotype when co-cultured with tumor cells. The reactive CAFs showed higher expression of α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP) compared to differentiated CAFs, when co-cultured with PC cells at the same experimental conditions. Together, we found that the activation mechanism of NF to CAF comprises different stages that progress from a reactive to quiescent cellular state in which these two states are differentiated by the fluctuation of intensity in CAF markers. Here we determined that a reactive state of CAFs proved to be important for supporting tumor cell survival and proliferation. These findings suggest the use of CAFs as a marker for cancer progression and a potential target for novel cancer therapeutics to treat metastatic disease. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27510 Press release - https://www.oncotarget.com/news/pr/cancer-associated-fibroblasts-confer-shear-resistance-to-circulating-tumor-cell/ Keywords - metastasis, cancer associated fibroblasts, circulating tumor cells, cytoprotection, collective migration About Oncotarget Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
This is today's edition of "A Fruitful Life" by Rick Clendenen. On this podcast, Bro. Rick brings us a special teaching entitled “Rick on CTCs and Youth”.
On this Tax Section Odyssey episode, April Walker, CPA, CGMA, Lead Manager — Association of International Certified Professional Accountants, representing AICPA & CIMA, and Larry Pon, CPA/PFS, CFP, EA, USTCP, AEP — Pon & Associates, review the changes to the 2021 child tax credit (CTC) and discuss the latest news regarding the related advanced payments. The American Rescue Plan Act enacted in March 2021 temporarily expands the CTC amount for certain taxpayers, made the credit fully refundable (meaning taxpayers can receive it even if they don't owe the IRS) and directs the IRS to make advance payments equal to 50% of IRS's estimate of the eligible taxpayer's 2021 CTCs during the period July 2021 through December 2021. In a letter currently being sent to taxpayers, the IRS explains that taxpayers will automatically receive advance CTC payments —assuming they are otherwise eligible to receive the CTC — for 2021. To date, the IRS has unveiled the following: Child Tax Credit Eligibility Assistant – allows families to answer a series of questions to determine whether they qualify for the advance payments Child Tax Credit Update Portal – allows families to verify their eligibility for the payments and gives them an option to unenroll from receiving the monthly payments Child Tax Credit Non-filer Sign-up Tool – allows families who are not required to file a tax return but who are otherwise eligible for the payments to report their qualifying children. What you'll learn in this episode Changes to the CTC for 2021 (1.13) What we know about the advance payments (3.50) How qualifying children are defined for the advance CTC (5.29) What practitioners should be discussing with clients in the next few weeks and related financial planning tips (6.28) Scenarios in which practitioners should advise clients to opt out of receiving advance payments and what is involved in the opt-out process (9.33) Tips for billing clients for work in this area (14.41) The CTC in 2022 and beyond (16.50) AICPA resources Child Tax Credit Client Letter – Client letter template for tax practitioners to use to notify their clients about the child tax credit changes and encourage clients to contact their CPA for additional tax and financial planning guidance. Child tax credit: New portal for opting out of advance payments – The Tax Adviser article published June 22, 2021 detailing the latest about the new portal. Other resources Advance Child Tax Credit Payments in 2021 – The IRS dedicated site that houses information related to the advance CTC payments as well as the eligibility assistant, update portal and non-filer sign-up tool 2021 Child Tax Credit and Advance Child Tax Credit Payments Frequently Asked Questions – Consolidation of answers to frequently asked questions related to the CTC and the advanced payments, separated by topic Proc. 2021-24 – Procedures for individuals who are not otherwise required to file federal income tax returns for taxable year 2020 to receive advance child tax credit payments under Sec. 7527A. Note, if your podcast app does not hyperlink to resources, visit https://taxodyssey.libsyn.com to access show notes with direct links. This episode is brought to you by the AICPA's Tax Section, your home base to maintain your professional edge. To learn more about the Tax Section, check out aicpa.org/tax or sign up for a free web tour.
RUBYnanomed was founded in 2018 as a spin-off of INL and aims to bring lab discoveries to the clinical market. RUBYnanomed focusses on non-invasive monitoring of cancer progression through liquid biopsy. Cancer is a major cause of morbidity and mortality worldwide (9.6 million deaths in 2018), but 90 % of those deaths are due to cancer spreading or metastasis. RUBYnanomed has developed the RUBYchip™, a microfluidic device for fast isolation of circulating tumour cells (CTCs), the cells responsible for metastasis, from unprocessed whole blood samples. Through the analysis of these cells, RUBYnanomed offers a non-invasive and real-time snapshot of cancer progression to oncologists. Visit their website to learn more: https://www.rubynanomed.com/ For questions or comments, please email us at info@inam.berlin. Also, if you or someone you know would like to be a guest on our show, we welcome any and all suggestions! Special thanks to Oxygen Sound Studios Track: Coastline — Ason ID [Audio Library Release] Music provided by Audio Library Plus Watch: https://youtu.be/B8TyOnh8S-U Free Download / Stream: https://alplus.io/_coastline The road by Esteban Orlando https://soundcloud.com/orlando-esteban-2 Creative Commons — Attribution-ShareAlike 3.0 Unported — CC BY-SA 3.0 Free Download / Stream: http://bit.ly/2QqI03Z Music promoted by Audio Library https://youtu.be/TsKWeCcjaBg
show notes @ https://thesternmethod.com/circulatingtumorcells/ KEY TAKEAWAYS 1. What are CTCs and what do they mean? Cells from a collection of cancer cells, tumor or metastatic deposit Sometime seen on scans but not always Circulate in the blood or lymphatic tissues Can only test for the CTC in blood. Need biopsy to detect in lymphatic tissue The presence of CTCs doesn’t necessarily indicate metastatic cancer CTCs don’t live very long in the blood – persistent CTC is cause for concern Cancer spreads in two ways Metastasize (means “evil spread”) - cells travel via blood vessels Direct invasion - cells invade the tissues and then access lymphatic system or blood stream What to look for in CTC testing Only available for certain cancers – ovarian, pancreatic, colon, lung, breast, prostate Looking for two different populations of CTCs- cytokeratin(CK)-positive and CK-negative ➔ CK is an anchor molecule for cells ➔ CK-negative cells are cells that have down regulated their CK and can leave the tissue space to ‘circulate’ as a CTC ➔ CK-positive cells are rarely found in CTC tests unless through trauma or if the tumor is invasive ➔ CK-negative cells can revert back to CK-positive and “anchor in” to a new tissue site Test results provide highly individual information about that person’s specific tumor Can also see some markers you’d see on pathology specimens - things that sit on the surface of cells such as androgen and estrogen receptors Hosted By: 2. 3. 29 When to test for CTCs At diagnosis and before treatment, when cancer is the highest During treatment to gauge therapeutic response Post treatment testing to determine if cancer is still present or to identify recurrences What to do with CTC test results Depends on the patient – their history, the cancer, how aggressive, treatment proto- cols undertaken. Every situation/person is different Run other lab tests to look at supporting factors in the blood and fix those: ➔ Inflammatory markers ➔ Cell markers ➔ Immune markers ➔ Tissue markers ➔ Hormones ➔ Tissues at risk – liver, lung, bones ➔ Nutrient levels ➔ Vitamin D – 25-Hydroxy and 1,25-Dihydroxy ➔ Look at lifestyle – diet, toxins, air, water Goal is to shut down the flow of CTC into the blood CASE STUDIES / CLINICAL EXAMPLES / DIAGNOSES REFERENCED Breast cancer Colon cancer Lung cancer Ovarian cancer Pancreatic cancer Prostate cancer STUDIES / ARTICLES / CLINICAL TRIALS REFERENCED N/A BOOKS REFERENCED N/A Hosted By: 30 SUPPLEMENTS REFERENCED N/A THERAPIES REFERENCED IV Vitamin C IV Quercetin Mistletoe therapy OTHER RESOURCES Biocept FOLLOW DR RUBIN Listenandcare.com Aspenmedcenter.com PH: 480.990.1111 Remote consultations available
A number of groundbreaking and practice-changing studies were presented at the San Antonio Breast Cancer Symposium 2020. The RxPONDER, ADAPT, and PRIME-2 trials revealed patients who can forgo chemotherapy or radiotherapy, monarchE and PENELOPE-B showed conflicting results with CDK4/6 inhibitors, one study indicated that a new tool can guide adjuvant chemotherapy, and another study suggested that circulating tumor cells (CTCs) can predict overall survival (OS). Alan P. Lyss, MD, subprincipal investigator for Heartland Cancer Research NCORP, joined host David H. Henry, MD, to discuss these and other studies — their top 10 presentations from SABCS 2020 — in this episode. 1. Abstract GS3-07. Identifying patients whose symptoms are under-recognized during breast radiotherapy: Comparison of patient and physician reports of toxicity in a multicenter cohort. https://bit.ly/2MGCVEH This presentation could be one of the most important stories to emerge from SABCS 2020, according to Dr. Lyss. The trial included 9,868 breast cancer patients who received radiotherapy over an 8-year period. Investigators compared patient and physician reports of toxicity during radiotherapy, assessing four symptoms: pain, pruritus, edema, and fatigue. Physicians under-recognized moderate to severe pain 30.9% of the time, pruritus 36.7% of the time, edema 51.4% of the time, and fatigue 18.8% of the time. “The bottom line is: We’ve got to do better at this, and the first step in correcting it is to acknowledge that there is a problem. This abstract established that,” Dr. Lyss said. 2. Abstract GS2-03. Prime 2 randomised trial (postoperative radiotherapy in minimum-risk elderly): Wide local excision and adjuvant hormonal therapy +/- whole breast irradiation in women =/> 65 years with early invasive breast cancer: 10-year results. https://bit.ly/3omINAL The trial enrolled 1,326 women with histologically confirmed, unilateral invasive, hormone receptor-positive (HR+) breast cancer who were all 65 or older, had a tumor measuring 3 cm or less, had no nodal involvement, and were about to undergo breast-conserving surgery. The women were randomized 1:1 to receive adjuvant whole-breast irradiation or no radiotherapy in addition to adjuvant endocrine therapy. At 10 years, the rate of ipsilateral recurrence was significantly lower with radiotherapy than without it (0.9% vs 9.8%, P = .00008). The 10-year rate of regional recurrence was significantly lower with radiotherapy as well (0.5% vs. 2.3%, P = .014). There was no significant difference in the radiotherapy and no-radiotherapy arms when it came to distant recurrence (3.6% vs. 1.9%, P = .07), contralateral recurrence (2.2% vs. 1.2%, P = .20), non–breast cancer (8.7% vs. 10.2%, P = .41), metastasis-free survival (96.4% vs. 98.1%, P = .28), or OS (81.0% vs. 80.4%, P = .68). These results suggest radiotherapy could be omitted in this patient population, but the decision should be discussed and tailored to the individual patient, according to Dr. Henry. 3. Abstract GS1-01. Primary outcome analysis of invasive disease-free survival for monarchE: abemaciclib combined with adjuvant endocrine therapy for high-risk early breast cancer. https://bit.ly/38oSHwt The monarchE trial enrolled 5,637 women with HR+, HER2- early breast cancer. Cohort 1 included patients with four or more positive nodes, up to three positive nodes and a tumor size ≥ 5 cm, or grade 3 disease. Cohort 2 included women with up to three positive nodes and a Ki-67 index ≥ 20%. Patients in both cohorts were randomized to standard endocrine therapy alone or standard endocrine therapy with abemaciclib. The 2-year rate of invasive disease-free survival (IDFS) was 92.3% in the abemaciclib arm and 89.3% in the control arm (P = .0009). The 2-year distant relapse-free survival rate was 93.8% and 90.8%, respectively (P = .0009). Dr. Lyss said this is the first real advance in HR+ breast cancer adjuvant treatment in many years and has the potential to save thousands of lives. However, these are early data and should be interpreted with caution. 4. Abstract GS1-02. Phase III study of palbociclib combined with endocrine therapy (ET) in patients with hormone-receptor-positive (HR+), HER2-negative primary breast cancer and with high relapse risk after neoadjuvant chemotherapy (NACT): First results from PENELOPE-B. https://bit.ly/2XeQvRs The PENELOPE-B trial enrolled 1,250 women who had completed neoadjuvant chemotherapy and locoregional therapy. They were randomized to palbociclib plus endocrine therapy or endocrine therapy plus placebo. There was no significant difference in IDFS with palbociclib or placebo at 2 years (88.3% vs. 84%), 3 years (81.2% vs. 77.7%), or 4 years (73% vs. 72.4%). 5. Abstract GS4-10. Development and validation of a tool integrating the 21-gene recurrence score and clinicopathologic features to individualize prognosis for distant recurrence and prediction of absolute chemotherapy benefit in early breast cancer. https://bit.ly/38htoMD The RSClin tool integrates the 21-gene recurrence score and clinicopathologic features, including the grade of the tumor, the tumor size, and the patient's age. Researchers found that RSClin could guide adjuvant chemotherapy in HR+, HER2-, axillary node-negative breast cancer with greater precision, when compared with clinicopathologic features or genomic data alone. RSClin is available at https://online.genomichealth.com/. 6. Abstract GS4-08. Clinical utility of repeated circulating tumor cell (CTC) enumeration as early treatment monitoring tool in metastatic breast cancer (MBC) - a global pooled analysis with individual patient data. https://bit.ly/2MGUrZp This study included 4,079 metastatic breast cancer patients who had undergone baseline and follow-up CTC measurements in previous trials. The investigators analyzed changes in CTC levels between baseline and follow-up to determine whether those levels were associated with OS. The median OS was 47 months for patients who were CTC-negative at both baseline and follow-up, 32.2 months for patients who were positive at baseline and negative at follow-up, 29.6 months for patients who were negative at baseline and positive at follow-up, and 17.8 months for patients who were positive at both time points. With the negative-negative group as the reference, hazard ratios were 1.52 for the positive-negative group, 1.74 for the negative-positive group, and 3.15 for the positive-positive group (P < .0001 for all). 7. Abstract GS3-00. First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) < 25: SWOG S1007 (RxPonder). https://bit.ly/35bK7Px RxPONDER included 5,083 adults with HR+, HER2- breast cancer, one to three positive nodes, no contraindications to taxane and/or anthracycline-based chemotherapy, and recurrence scores of 25 or below. Patients were randomized 1:1 to receive endocrine therapy or chemo-endocrine therapy using three stratification factors: recurrence score (0-13 vs.14-25), menopausal status, and axillary nodal dissection vs. sentinel node biopsy. At a median follow-up of 5.1 years, there was no association between chemotherapy benefit and recurrence score values in the whole study population. In postmenopausal patients, there was no difference in 5-year IDFS between patients who received chemotherapy and those who didn’t (91.6% vs. 91.9%, P = .82). However, in premenopausal patients, the 5-year IDFS rate was 94.2% with chemotherapy and 89% without it (P = .0004). The data also showed an OS benefit with chemotherapy in premenopausal patients (P = .032), although this result is considered early due to few deaths at the time of evaluation. “These data really establish that postmenopausal women with between one to three involved nodes and an Oncotype DX score of 25 or less do not need post-operative adjuvant chemotherapy; end of discussion,” Dr. Lyss said. “For physicians who have been giving those women chemotherapy, these data are immediately practice- changing.” 8. Abstract GS4-04. Endocrine therapy alone in patients with intermediate or high-risk luminal early breast cancer (0-3 lymph nodes), Recurrence Score 10% or the patient had clinical N2 or N3 lymph nodes, the patient was assigned to receive neoadjuvant chemotherapy. The 5-year IDFS rate was 92.6% in patients with a recurrence score of 12-25 and a Ki-67 response and 93.9% in patients with a recurrence score of 0-11. The 5-year distant relapse-free survival was 95.6% and 96.3%, respectively. The 5-year OS was 97.3% and 98%, respectively. These results suggest Oncotype DX testing could spare the majority of HR+, HER2- patients with zero to three positive lymph nodes from receiving chemotherapy, Dr. Lyss said. 9. Abstract GS3-01. Additional efficacy endpoints from the phase 3 KEYNOTE-355 study of pembrolizumab plus chemotherapy vs placebo plus chemotherapy as first-line therapy for locally recurrent inoperable or metastatic triple-negative breast cancer. https://bit.ly/394UCVX In KEYNOTE-355, 847 patients with locally recurrent, inoperable or metastatic triple-negative breast cancer were randomized to receive pembrolizumab plus chemotherapy or chemotherapy plus placebo. Chemotherapy consisted of nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin. The median progression-free survival (PFS) was longer in the pembrolizumab arm, at 7.5 months, versus 5.6 months with chemotherapy alone (hazard ratio, 0.82). The PFS was superior with pembrolizumab regardless of the chemotherapy partner. However, higher PD-L1 expression was associated with a longer PFS, a higher overall response rate, and a longer duration of response. 10. Abstract GS3-06. Biomarker evaluation in the phase 3 ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer. https://bit.ly/3hQ14nJ Trophoblast cell-surface antigen-2 (Trop-2) is highly expressed in triple-negative breast cancer. Sacituzumab govitecan (SG) consists of an anti-Trop-2 antibody coupled to SN-38, an active metabolite of irinotecan. In the ASCENT trial, patients with metastatic triple-negative breast cancer were randomized to SG or standard single-agent chemotherapy. A subgroup analysis of this trial showed that Trop-2 levels correlated with PFS and OS. Patients were divided into three groups by Trop-2 levels — low (H-score
Blood & Cancer news stories: Black patients with ES-SCLC get less chemo but have better survival: https://bit.ly/33Rb5eB Should CTCs guide treatment choice in HR+, HER2– breast cancer?: https://bit.ly/3gn6shc New drug approved for relapsed/refractory neuroblastoma: https://bit.ly/2VMpvIy FDA approves first agent for PSMA-PET imaging in prostate cancer: https://bit.ly/36TAaY7 Contact Blood & Cancer at podcasts@mdedge.com.
The @ReicherCougars fought back from an early deficit to top CTCS 27-22 in the 2nd round of the TAPPS playoffs. Hear how it happened with the highlights. #TXHFSB
Interview with Bryan P. Schneider, MD, and Milan Radovich, PhD, authors of Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy With Disease Recurrence in Patients With Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial
Interview with Bryan P. Schneider, MD, and Milan Radovich, PhD, authors of Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy With Disease Recurrence in Patients With Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial
Back by popular demand! Associate Professor Dr Karin Ried joins Nathan to discuss the National Institute of Integrative Medicine’s ISET®-CTC test. Ried explains how the test detects CTCs, including how it can distinguish between malignant CTCs and benign circulating epithelial cells, as well as nuances around interpretation of results and the value of monitoring CTCs. Enjoy the highly informative conversation with Dr Ried. *Highlights * A very good place to start – what is a CTC? (1:30) The role the ISET®-CTC test has in integrative oncology (8:00) Nuances around result interpretation (12:40) Comparing this test to marker tests (21:20) Emphasis on the role of the immune system (29:50) Delivering results to patients (33:20) Delving into cancer screening (39:00) Learnings from examining prostate cancer (40:00) The value of monitoring CTCs (53:30) Therapeutic considerations (105:00) Useful links and resources: e.g: Follow Metagenics Instagram - @metagenics_anz or Facebook - https://www.facebook.com/metagenics/ If you hold a Metagenics account in Australia or New Zealand join our Facebook Group here - https://www.facebook.com/groups/MetagenicsAU/ Paper – ‘New Screening Test Improves Detection of Prostate Cancer Using Circulating Tumor Cells and Prostate-Specific Markers’ - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192049/
Back by popular demand! Associate Professor Dr Karin Ried joins Nathan to discuss the National Institute of Integrative Medicine’s ISET®-CTC test. Ried explains how the test detects CTCs, including how it can distinguish between malignant CTCs and benign circulating epithelial cells, as well as nuances around interpretation of results and the value of monitoring CTCs. Enjoy the highly informative conversation with Dr Ried. *Highlights * A very good place to start – what is a CTC? (1:30) The role the ISET®-CTC test has in integrative oncology (8:00) Nuances around result interpretation (12:40) Comparing this test to marker tests (21:20) Emphasis on the role of the immune system (29:50) Delivering results to patients (33:20) Delving into cancer screening (39:00) Learnings from examining prostate cancer (40:00) The value of monitoring CTCs (53:30) Therapeutic considerations (105:00) Useful links and resources: e.g: Paper – ‘New Screening Test Improves Detection of Prostate Cancer Using Circulating Tumor Cells and Prostate-Specific Markers’ - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192049/
I’m back giving you the second update in this content series about what is going on with 4x400, the holding company for the brands that we at Common Thread Collective own ourselves. Last time I talked to you, I told you about how we were in a cash crunch. We basically had $300k in liabilities against $120k in the bank, plus a $70k payroll — and it was a huge challenge in front of us. That was going into the Black Friday,Cyber Monday weekend. Now that it's over, the results are in. Here’s a big takeaway for me from Black Friday this year that I saw across the board: our brands, CTCs, and everybody else ...
Ira Pastor, ideaXme exponential health ambassador, interviews Dr. Ronald Mallett, Professor Emeritus, Theoretical Physics, Department of Physics at the University of Connecticut. Ira Pastor Comments: Time travel is the concept of movement between certain points in time, analogous to movement between different points in space, by an object or a person, typically with the use of a hypothetical device known as a time machine. Time travel is a widely recognized concept in philosophy and fiction and the idea of a time machine was originally popularized by H. G. Wells' 1895 novel The Time Machine. Forward time travel, outside the usual sense of the perception of time, is an extensively observed phenomenon and well-understood within the framework of special relativity and general relativity and making one body advance a few milliseconds compared to another body has been demonstrated in experiments comparing atomic clocks on jets and satelites versus the earth. As for backward time travel, it is possible to find solutions in general relativity that allow for it, in a theoretical system known as a "closed timelike curve" (sometimes abbreviated CTC), which is where the world line of an object (the path that an object traces in 4-dimensional space-time) follows a curious path where it eventually returns to the exact same coordinates in space and time that it was at previously. In other words, a closed timelike curve is the mathematical result of physics equations that allows for time travel to the past. Dr. Ronald Mallett Our guest today who has been at the forefront of theoretical research in this area, and who has been developing some rather novel theories on the ways that light, specifically laser light, may be able to create CTCs, is Dr. Ronald Mallett, Professor Emeritus, Theoretical Physics, Department of Physics at the University of Connecticut. With a BS, MS, and PhD in Physics from Pennsylvania State University, Dr. Mallett has lectured over the past few decades in such diverse areas as general relativity and gravitation, black holes, relativistic astrophysics, quantum cosmology, gauge theories, and time travel. He has published numerous papers on black holes and cosmology in professional journals. Dr. Mallett's papers related to his time travel interests (also known as the "Space-time Twisting by Light(STL)" project), include "Weak Gravitational Field of the Electromagnetic Radiation in a Ring Laser", "Gravitational Faraday Effect Produced by a Ring Laser", and "The Gravitational Field of a Circulating Light Beam." His breakthrough research on theoretical time travelhas been featured extensively in the media around the world, including NPR’s This American Life, the History Channel, Science Channel, and Learning Channel. He is author of Time Traveler: A Scientist’s Personal Mission to Make Time Travel a Reality. On this episode of ideaXme we will hear from Dr. Mallett: About his background, how he developed an interest in physics, Albert Einstein, time travel theory. We'll learn about CTCs, gravity, and light frame-dragging of time theories. What it is like in the area of physics to investigate such "science fiction" topics. His thoughts on various time travel paradoxes and retro-causality. Credits: Ira Pastor interview video, text, and audio. Follow Ira Pastor on Twitter:@IraSamuelPastor If you liked this interview, be sure to check out ourinterview on Building a Synthetic Brain with Dr. Alice C. Parker! Follow ideaXme on Twitter:@ideaxm On Instagram:@ideaxme Find ideaXme across the internet including oniTunes,SoundCloud,Radio Public,TuneIn Radio,I Heart Radio, Google Podcasts, Spotify and more. ideaXme is a global podcast, creator series and mentor programme. Our mission: Move the human story forward!™ ideaXme Ltd.
Heather and Logan are back to talk about the science of witches and witchcraft! Grab your brooms and clean your cauldrons, because these pals take a dive into the history and context of witches and witchcraft. Listen to learn about what eye of newt, tongue of dog, and adder's fork actually are; and the conflicting theories on what the deal is with witches' hats. Love the pod? Go over to Apple Podcasts and rate us 5 stars to help boost CTCS! Thanks for listening! Keep sciencing!
Join us as we speak with Senate President Carmichael about Senate Bill 1 (the Last Dollar In Tuition Bill) and the WV Invests Grant program.
086 | Paving the way of the future Welcome to another episode of Biotechnology Focus radio! This week Toronto got their socks knocked off by an announcement from Sanofi; a Chinese company expresses interest in some of Canada’s regenerative medicine technologies; the scope of clinical trials in Canada is divulged at the recent Clinical Trials Ontario conference; and Shana Kelley and her team from the University of Toronto use new technology to essentially ‘find a needle in a haystack’ when it comes to prostate cancer. Keep listening to hear the latest news of Canada’s biotech scene! +++++ French company Sanofi announces one of their largest investments ever in a single building and knocks the socks off the Toronto life sciences community. Sanofi announces that they are investing €350 million (C$500 million) into their Toronto facility to significantly increase capacity to meet the growing demand for pediatric and booster vaccines and demonstrate their commitment to innovation and leadership in global health. The announcement was held at Sanofi Pasteur’s Canadian headquarters in Toronto and was joined by the Honourable Navdeep Bains, Minister of Innovation, Science and Economic Development, and the Honourable Steven Del Duca, Minister of Economic Development and Growth. Canada has a strong legacy in the research and development of vaccines. With this investment, Sanofi is renewing their longstanding commitment to making Canada central in the effort to protect and improve human health across the globe. Vaccines save three million lives every year and this new facility will be one step closer to a world where no one suffers or dies from a vaccine-preventable disease. The new facility will allow Sanofi Pasteur, the vaccines global business unit of Sanofi, to meet the growing demand of five-component acellular pertussis (5-acP) antigen. The building itself is expected to be completed within three to four years, a year or two to get the quality management system up and running, and a year or two to do product development and testing. The site will be equipped to produce the antigens used in the diphtheria and tetanus vaccines. Philippe Luscan, the executive vice president of Global Industrial Affairs, Sanofi says that this project is one of the most important investments for the Sanofi global industrial network. It demonstrates the continued commitment to manufacturing excellence and to better serving their vaccines portfolio to people all over the world. ++++++ New opportunities are arising at every turn for the regenerative medicine community. Research is at the tip of the iceberg, but a company in British Columbia isn’t waiting for the ice to melt. RepliCel, a regenerative medicine company, has been developing autologous cell therapies to treat conditions linked to the deficit of healthy cells required for normal function and healing. Their cell therapies are designed to treat chronic tendinosis, UV-damaged or aged skin, and pattern baldness as an alternative method to surgery, pills, and chemicals. Recently, YOFOTO, one of China’s largest health and wellness companies announced its intention to invest significant financial backing into the company to market RepliCel’s tendon repair and skin rejuvenation products – and they are not the only one – Shiseido, another giant, has been developing RepliCel’s hair regeneration technology for the Asian market. Last year hit significant milestones for the company with production of the first fully functioning prototypes of their next generation dermal injector that is optimal for the delivery of injectables into the skin. With patents already issued in the United States and in Europe, the functioning prototypes allow RepliCel to display the applications of the device with other potential partners as they move forward at finalising the mold for the commercial-ready devices. Last year also saw new clinical data produced on all three biologics programs – thinning hair (androgenic alopecia), aging/sun-damaged skin, and chronic tendinopathy (Achilles Tendinosis). The phase 1 clinical data demonstrated overwhelming product safety and highly encouraging signals of product efficacy to regrow hair, rejuvenate skin, and regenerate tendon tissue. In 2013, RepliCel executed a co-development and licensing agreement with Shiseido that covered all of Asia for their hair regeneration program. Now, with the potential for another deal emerging in Greater China, we have real opportunity to leverage these partnerships to be a leader in regenerative medicine platform across Asia. According to Brad Loncar, who recently launched a China BioPharm Index Fund, following the success of his Cancer Immunotherapy Fund, the biotechnology and pharmaceutical sectors are headed for exponential growth in the next few years and cell therapies are a significant focus in Greater China where he believes they are “ahead of the curve”. Indeed, last month, the Chinese government unveiled its Made In China 2025 industrial plan in which it laid out a strategy for revolutionizing the Chinese biopharmaceutical industry through major investments in the sector and its supporting infrastructure. It is a very exciting time for RepliCel as they move forward with a CE mark for their device in Europe and their potential expansion in Asia, as well as refining their US strategy for the launch of their dermal injector. With fascinating development projects in queue and continuing to look for the right opportunities, there will be substantial progress that will come from this innovative regenerative medicine company in the near future. ++++++ It would be too easy to say that the recent CTO 2018 Clinical Trials Conference was an immense success – but it was. A sold-out event with 400 people speaks for itself. It was held in Toronto at the Sheraton Centre Hotel over two days chalked full of intrinsic speakers and panels discussing clinical research, clinical trials, and patient engagement. The first day brought wonderful opening remarks from the Honourable Reza Moridi, Minister of Research, Innovation and Science, and was followed by Brian Goldman as the morning’s keynote speaker. Brian Goldman is an ER physician, author and radio broadcaster of CBC’s White Coat, Black Art but chose to direct his keynote towards clinical trials in the age of disruption. Disruptive innovation has become a powerful change in health care, amongst many other industries. He defined exactly what disruptive innovation was with recent examples and its potential implications in health care – clinical trials, big data, clinical research. To kick off the first panel was Jason Field, president and CEO of Life Sciences Ontario as a moderator of the evolving clinical research environment. The panel facilitated discussion on how to adapt to changes and how patients, health care and the economy will be impacted now and in the future. As the day progressed there were speakers touching on future strategies, why Canada has a health care system, the misalignment of evidentiary interests and clearing the path ahead. An engrossing one-on-one interview after lunch with Francis Plummer, professor of medicine and medical microbiology from the University of Manitoba about a lesson in preparedness and how his work with the Ebola vaccine was a prime example of pre-empting what may happen, so that when and if it does, society will have a cure or at least a way to face it. Clinical trials simply do not happen without participants, so the second panel brought patients and caregivers of patients to the stage to share their stories and experiences. They brought to life what the health care community works for and to and their advice on helping others find and join a clinical trial was instrumental. The second day did not disappoint. Robert Bell, Minister of Health and Long-Term Care gave the opening remarks and welcomed the keynote speaker Ken Getz, director of sponsored research programs and research associate professor from the Tufts Center for the Study of Drug Development. Coincidently, he was also the keynote speaker at the very first Clinical Trials Conference that CTO put on a few years back; allowing him to describe first-hand how much it had grown and the benefits and impact this conference has on the clinical trials environment. He examined the current global operating environment for clinical research and specific areas where patient engagement practices and initiatives are being implemented. Patient engagement with clinical trials remains a hot topic and largely uncharted territory. The first panel explored these models of patient engagement to give a voice to patient perspectives, quality of life values, and treatment experiences so that the health care system can get access to the drugs patients need sooner and create more robust trials and outcomes. Following that, Molly Shoichet, Ontario’s first Chief Scientist was the interviewee of the day and went into detail about Canada’s research strengths, her aspirations for Ontario and Canada, and the innovation economy. The remaining panels covered current interests such as big data in healthcare to advance opportunity and mitigate privacy risks, and how to advance ways to streamline the conduct of clinical trials and make Ontario and Canada a better place to have them executed. They engaged the audience in fruitful discussions and answered many burning questions from the listeners. The two days compressed a wealth of knowledge, aspirations, and innovative ideas for the future of clinical trials in Ontario and Canada and left guests with an eagerness to start down that road. +++++ Researchers at the University of Toronto have developed an innovative technology to identify which patients might not respond to standard therapy for prostate cancer before it is delivered from a “liquid biopsy”. Prostate cancer is the most common cancer in men (excluding non-melanoma skin cancers) and third leading cause of death in Canada, according to the Canadian Cancer Society 2017 statistics. While several viable treatment options for prostate cancer exist, many men affected with prostate cancer will not respond to first-line treatments. Shana Kelley, a professor at the University of Toronto divulges that screening for drug resistance is key to improving treatment approaches for many cancers. It is important for patients not to be on a therapy that won’t help them and it’s also important for health-care systems to avoid, whenever possible, delivering ineffective treatments. Creating an option for a “liquid biopsy” via a blood test instead of more invasive alternatives is a step in the right direction and will save time, money, and recuperation time. Kelley, lead investigator on the study published in Nature Chemistry, explains how her team has advanced a completely new approach using magnetic nanoparticles with DNA capture probes on their surface that can target circulating tumour cells (CTCs) in blood samples to see if the cells contain biomarkers associated with drug resistance. The team traps the individual magnetized cells in a microfluidic device built in the lab, isolating them from all the other cells in the sample and allowing them to perform highly sensitive analysis. The cells with the highest magnetic content will also have a high messenger RNA expression for the biomarker associated with drug resistance. This means that patients with high messenger RNA expression should be considered for other therapies because they won’t respond to the first-line treatment. Being able to access the circulating tumour cells CTC cells is critical in the fight against cancer, as they carry information from the primary tumour that will divulge the best form of treatment for the patient. They are, however, outnumbered by a billion-to-one by normal cells in a patient’s blood making catching them a very daunting task. In 2016, Kelley and her team published a study in Nature Nanotechnology that first introduced the microfluidic device and how it could be used to trap and analyze circulating tumour cells CTCs. The current study builds on this work by further targeting a specific biomarker within the circulating tumour cells CTCs. The blood samples analyzed were collected from a small cohort of patients undergoing treatment for metastatic prostate cancer. In 10 of the patients tested, circulating tumour cells CTCs were visualized but only four of the patients exhibited the biomarker associated with drug resistance. This finding demonstrates that the new method can provide both a circulating tumour cells CTC count and an analysis of the clinically relevant biomarker. “We are very excited because this is like finding a needle in a haystack,” says Kelley. “It paves the way for a straightforward and personalized screening tool that allows clinicians to see if a patient will respond to therapy or not. Our method is also rapid, accurate and inexpensive, which gives it real potential for clinical uptake.” Further studies need to be conducted to ensure consistent findings. Kelley and her team would also like to take this technology and expand it to other forms of cancer and disease. ++++++ Well that’s it for another episode of Biotechnology Focus radio! To read the stories in full check out our website at biotechnologyfocus.ca. Thank you for listening and have a great week ahead! From my desk to yours – this is Michelle Currie.
Institute of Historical Research Dr Elizabeth Bailey, University of Birmingham Education policy in England underwent major reform thirty years ago in terms of provision, curriculum, funding and management. City Technology Colleges (CTCs), proposed...
Dr Salomon Manier speaks with ecancer at the 16th International Myeloma Workshop about cell-free DNA (cfDNA) and circulating tumour cells (CTCs) sequencing that enable serial temporal sampling. The team looked at whole-exome sequencing (WES) and ultra low pass-whole genome sequencing (ULP-WGS) of cfDNA and CTCs in multiple myeloma. The study demonstrated that WES and ULP-WGS of cfDNA and CTCs are consistently representative of tumour DNA alterations in terms of CNAs and SNVs. This approach could therefore be used to longitudinally follow clonal evolution and minimal residual disease in MM, personalising and improving treatment. It also reduces the need for bone marrow biopsy, greatly improving the patient experience.
In New Jersey, each county has a Counterterrorism Coordinator (CTC), based out of the Prosecutor’s Office. These CTCs serve as the critical link between New Jersey’s municipalities, counties, the State, and the federal field offices. Each CTC works in conjunction with one another and the State to report and investigate suspicious activity occurring. This week, Monmouth County’s CTC Guy McCormick sits down with NJOHSP Intelligence Planner Jeff Elgrim to discuss the role of the CTCs in New Jersey and how the relationship between NJOHSP and the CTCs serves the residents of New Jersey.
Can you expect a colonoscopy performed via CT scan to be as accurate as a conventional colonoscopy? Physician Judy Yee of the University of California, San Francisco says innovative CT colonographies, or CTCs, are becoming a good alternative. "CT colonography is an imaging test that we would like to use for not only diagnosis of colorectal cancer, but for screening for colorectal cancer. There are many peer-reviewed papers and research that’s been done, including here, comparing the traditional CT colonography method to colonoscopy and have found that they’re pretty much equivalent for the clinically significant polyps. The true 3D, or the virtual holographic version of CT colonography is expected to be as accurate, if not more accurate." Yee is currently conducting larger studies on the procedure, which has proven to have multiple benefits. "So that’s another advantage, actually, of the CTC, is that you don’t need sedation at all."
Recently, there has been a push to develop alternative methods to traditional invasive techniques, such as solid tissue biopsies, for disease diagnosis and disease progression, as well as therapeutic response. Liquid biopsy is a new, minimally invasive technology for detecting circulating biomarkers without the need for costly or invasive procedures. Liquid biopsy enables users to sensitively, specifically and rapidly analyze circulating free nucleic acids (cfDNA), circulating tumor cells (CTCs) or exosomes from a blood sample. For more information please visit: http://bitesizebio.com/webinar/25528/liquid-biopsy-sample-handling/
Liquid biopsies (also called serum testing) is a practice already approved in Europe for EGFR lung cancer patients. Drawing blood to test for acquired resistance is easier and quicker than needle biopsies. How long until it is standard practice in the US?
Liquid biopsies (also called serum testing) is a practice already approved in Europe for EGFR lung cancer patients. Drawing blood to test for acquired resistance is easier and quicker than needle biopsies. How long until it is standard practice in the US?
Liquid biopsies (also called serum testing) is a practice already approved in Europe for EGFR lung cancer patients. Drawing blood to test for acquired resistance is easier and quicker than needle biopsies. How long until it is standard practice in the US?
Dr. Jack West reviews new techniques for evaluating mutations from blood, including detection of circulating tumor cells (CTCs) or mutations in circulating free DNA (cfDNA) that can replace at least some tissue biopsies.
Dr. Jack West reviews new techniques for evaluating mutations from blood, including detection of circulating tumor cells (CTCs) or mutations in circulating free DNA (cfDNA) that can replace at least some tissue biopsies.
Dr. Jack West reviews new techniques for evaluating mutations from blood, including detection of circulating tumor cells (CTCs) or mutations in circulating free DNA (cfDNA) that can replace at least some tissue biopsies.
Acquired Resistance Forum Video #3: Dr. Lecia Sequist of Massachusetts General Hospital detailed why doctors started doing repeat biopsies for patients receiving targeted therapies and how they help patients and doctors determine next steps in treatment.
Acquired Resistance Forum Video #3: Dr. Lecia Sequist of Massachusetts General Hospital detailed why doctors started doing repeat biopsies for patients receiving targeted therapies and how they help patients and doctors determine next steps in treatment.
Acquired Resistance Forum Video #3: Dr. Lecia Sequist of Massachusetts General Hospital detailed why doctors started doing repeat biopsies for patients receiving targeted therapies and how they help patients and doctors determine next steps in treatment.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 17/19
It is widely known that cells from epithelial tumors, e.g., breast cancer, detach from their primary tissue and enter blood circulation. We show that the presence of circulating tumor cells (CTCs) in samples of patients with primary and metastatic breast cancer can be detected with an array of selected tumor-marker-genes by reverse transcription real-time PCR. The focus of the presented work is on detecting differences in gene expression between healthy individuals and adjuvant and metastatic breast cancer patients, not an accurate quantification of these differences. Therefore, total RNA was isolated from blood samples of healthy donors and patients with primary or metastatic breast cancer after enrichment of mononuclear cells by density gradient centrifugation. After reverse transcription real-time PCR was carried out with a set of marker genes (BCSP, CK8, Her2, MGL, CK18, CK19). B2M and GAPDH were used as reference genes. Blood samples from patients with metastatic disease revealed increased cytokine gene levels in comparison to normal blood samples. Detection of a single gene was not sufficient to detect CTCs by reverse transcription real-time PCR. Markers used here were selected based on a recent study detecting cancer cells on different protein levels. The combination of such a marker array leads to higher and more specific discovery rates, predominantly in metastatic patients. Identification of CTCs by PCR methods may lead to better diagnosis and prognosis and could help to choose an adequate therapy.
Introduction: Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch® system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement. Methods: CellSearch® images (N = 272) of either CTCs or white blood cells or artifacts from 109 non-metastatic (M0) and 22 metastatic (M1) breast cancer patients from reported studies were sent to 22 readers from 15 academic laboratories and 8 readers from two Veridex laboratories. Each image was scored as No CTC vs CTC HER2-vs CTC HER2+. The 8 Veridex readers were summarized to a Veridex Consensus (VC) to compare each academic reader using % agreement and kappa (.) statistics. Agreement was compared according to disease stage and CTC counts using the Wilcoxon signed rank test. Results: For CTC definition (No CTC vs CTC), the median agreement between academic readers and VC was 92% (range 69 to 97%) with a median. of 0.83 (range 0.37 to 0.93). Lower agreement was observed in images from M0 (median 91%, range 70 to 96%) compared to M1 (median 98%, range 64 to 100%) patients (P < 0.001) and from M0 and < 3CTCs (median 87%, range 66 to 95%) compared to M0 and >= 3CTCs samples (median 95%, range 77 to 99%), (P < 0.001). For CTC HER2 expression (HER2-vs HER2+), the median agreement was 87% (range 51 to 95%) with a median. of 0.74 (range 0.25 to 0.90). Conclusions: The inter-reader agreement for CTC definition was high. Reduced agreement was observed in M0 patients with low CTC counts. Continuous training and independent image review are required.
From part one of the two-part JALA Special Issue on Advancements in Biomedical Micro/Nano Tools and Technology: three authors talk about metastatic dissemination and spread of malignant circulating tumor cells (CTCs) and how physical enrichment technologies may enable analysis of rare CTC phenotypes that may not be otherwise obtained.
ecancer reporter Peter Goodwin talks to Dr Navin at the 2013 IMPAKT conference in Brussels about the new technology of single cell sequencing. Blood tests allow the sampling of CTCs and thus the genome of any primary and metastatic tumours; this then allows the progress of a tumour to be monitored and it's repsonse to certain therapies. There is also potential for very early detection of tumours, and in the future a yearly test for early stage tumours which could lead to a huge reduction in deaths from cancer.
Breast cancer is still the most frequent cause of cancer-related death in women worldwide. Often death is not caused only by the primary tumour itself, but also by metastatic lesions. Today it is largely accepted, that these remote metastases arise out of cells, which detach from the primary tumour, enter circulation, settle down at secondary sites in the body and are called Circulating Tumour Cells (CTCs). The occurrence of such minimal residual diseases in the blood of breast cancer patients is mostly linked to a worse prognosis for therapy outcome and overall survival. Due to their very low frequency, the detection of CTCs is, still a technical challenge. RT-qPCR as a highly sensitive method could be an approach for CTC-detection from peripheral blood of breast cancer patients. This assumption is based on the fact that CTCs are of epithelial origin and therefore express a different gene panel than surrounding blood cells. For the technical approach it is necessary to identify appropriate marker genes and to correlate their gene expression levels to the number of tumour cells within a sample in an in vitro approach. After that, samples from adjuvant and metastatic patients can be analysed. This approach may lead to new concepts in diagnosis and treatment
It is widely known that cells from epithelial tumors, e. g., breast cancer, detach from their primary tissue and enter blood circulation. We show that the presence of circulating tumor cells (CTCs) in samples of patients with primary and metastatic breast cancer can be detected with an array of selected tumor-marker-genes by reverse transcription real-time PCR. The focus of the presented work is on detecting differences in gene expression between healthy individuals and adjuvant and metastatic breast cancer patients, not an accurate quantification of these differences. Therefore, total RNA was isolated from blood samples of healthy donors and patients with primary or metastatic breast cancer after enrichment of mononuclear cells by density gradient centrifugation. After reverse transcription real-time PCR was carried out with a set of marker genes (BCSP, CK8, Her2, MGL, CK18, CK19). B2M and GAPDH were used as reference genes. Blood samples from patients with metastatic disease revealed increased cytokine gene levels in comparison to normal blood samples. Detection of a single gene was not sufficient to detect CTCs by reverse transcription real-time PCR. Markers used here were selected based on a recent study detecting cancer cells on different protein levels. The combination of such a marker array leads to higher and more specific discovery rates, predominantly in metastatic patients. Identification of CTCs by PCR methods may lead to better diagnosis and prognosis and could help to choose an adequate therapy.
Dr Ged Brady talks to ecancer at the European Forum on Oncology in Berlin, May 2012 about the concept behind the EurocanPlatform and combining the resources of institute in order to create normalised templates for therapy and identifying biomarkers. Prof Brady finds that in practice, oncologists communicate and learn through journals and conferences, but there is a need for talking to peers and learning from them. Platforms like this allow institutes and members of those institutes to bring together ideas and resources with a strong focus. Early examples of sharing methodologies and results at the Paterson Institute for Cancer Research have been in the field of circulating tumour cells (CTCs) and the technology that allows for their isolation and numeration.
Prof Giuseppe Curigliano talks to ecancer about the heterogeneity of tumours and the challenges of biomarker development at IMPAKT 2012 in Brussels, May 2012. Specific mutations like PI3K mutation or p54 mutation provide targetable mutations for drug development; however, mutations found in the primary tumour are not the same as the metastatic tumour. Once a tumour is present, significant changes occur in the body and to the immune system when the tumour metastases treatment needs to focus on the microenvironment. Research conducted on future treatments involves CTCs, bone cells and tools to quickly characterise tumours.
Introduction: There is a multitude of assays for the detection of circulating tumor cells (CTCs) but a very limited number of studies comparing the clinical relevance of results obtained with different test methods. The DETECT trial for metastatic breast cancer patients was designed to directly compare the prognostic impact of two commercially available CTC assays that are prominent representatives of immunocytochemical and RT-PCR based technologies. Methods: In total, 254 metastatic breast cancer patients were enrolled in this prospective multicenter trial. CTCs were assessed using both the AdnaTest Breast Cancer and the CellSearch system according to the manufacturers' instructions. Results: With the CellSearch system, 116 of 221 (50%) evaluable patients were CTC-positive based on a cut-off level at 5 or more CTCs. The median overall survival (OS) was 18.1 months in CTC-positive patients. (95%-CI: 15.1-22.1 months) compared to 27 months in CTC-negative patients (23.5-30.7 months; p
B-roll of Noble Eagle, Sept 14th 2001. Scenes include aerial footage of the damage caused to the Pentagon after being attacked during the events of Sept. 11, 2001. Produced by Tech Sgt. T. Szestowicki - 1st CTCS, Charleston. 911TenAnniv
B-roll of Noble Eagle, Sept 14th 2001. Scenes include various footage of the damage caused to the Pentagon after being attacked during the events of Sept. 11, 2001. Produced by Staff Sgt. David Barlow - 1st CTCS, Charleston. Part 1 of 3. 911TenAnniv
B-roll of Noble Eagle, Sept 14th 2001. Scenes include various footage of the damage caused to the Pentagon after being attacked during the events of Sept. 11, 2001. Produced by Staff Sgt. David Barlow - 1st CTCS, Charleston. Part 2 of 3. 911TenAnniv
B-roll of Noble Eagle, Sept 14th 2001. Scenes include various footage of the damage caused to the Pentagon after being attacked during the events of Sept. 11, 2001. Produced by Staff Sgt. David Barlow - 1st CTCS, Charleston. Part 3 of 3. 911TenAnniv
Introduction: Circulating tumor cells (CTCs) reflect aggressive tumor behavior by hematogenous tumor cell dissemination. The tissue inhibitor of metalloproteinase 1 (TIMP-1) plays a role in tissue invasion and is also involved in angiogenesis, abrogation of apoptosis and in chemoresistance. Carbonic anhydrase IX (CAIX) is a metalloenzyme involved in cell adhesion, growth and survival of tumor cells. The aim of the study was to investigate whether serum concentrations of TIMP-1 and CAIX are associated with the detection of CTC in metastatic breast cancer. Methods: Blood was obtained in a prospective multicenter setting from 253 patients with metastatic breast cancer at the time of disease progression. Serum TIMP-1 and CAIX were determined using commercial ELISA-kits (Oncogene Science). CTC were detected with the CellSearch (TM) system (Veridex). Results: Five or more CTCs were detected in 122 patients out of 245 evaluable patients (49.8%). Out of 253 metastatic patients 70 (28%) had serum TIMP-1 levels above 454 ng/mL. Serum CAIX was elevated above 506 ng/mL in 90 (35%) patients. Both serum markers had prognostic significance. Median progression free survival (PFS) was 7.2 months with elevated TIMP-1 vs. 11.4 months with non-elevated levels (p < 0.01). OS was 11.5 vs. 19.1 months (p < 0.01). Median PFS was 7.5 months with elevated CAIX vs. 11.7 months with non-elevated levels (p < 0.01), overall survival (OS) was 13.4 months vs. 19.1 months (p < 0.01). In patients with five or more CTCs, serum levels were above the cut-off for CAIX in 47% vs. 25% in those with less than five CTCs (p = 0.01). For TIMP-1, 37% patients with five or more CTCs had elevated serum levels and 17% of patients with less than five CTCs (p = 0.01). Including TIMP-1, CAIX, CTC and established prognostic factors in the multivariate analysis, the presence of CTCs, the therapy line and elevated CAIX remained independent predictors of OS. Conclusions: Elevated serum levels of the invasion markers TIMP-1 and CAIX in metastatic breast cancer are prognostic markers and are associated with the presence of CTCs. Whether increased secretion of TIMP-1 and/or CAIX might directly contribute to tumor cell dissemination remains to be elucidated in further investigations.
Emma Grainger discusses articles on myelodysplastic syndromes, circulating tumour cells and prostate cancer, and palliative stents for oesophageal cancer.
Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 03/07
Ziel dieser Arbeit war es BoHV-1 Doppeldeletionsmutanten zu generieren, zu charakterisieren und bezüglich ihrer Vakzineeignung zu bewerten. Die vorgestellten Studien zur Charakterisierung eines gE und UL49.5 deletierten Virus (BoHV-1-DgEDUL49.5) konnten belegen, dass diese Deletionskombination als letal für BoHV-1 anzusehen ist. Ein UL49.5 deletiertes Virus verhielt sich dagegen funktionell wie ein Virus ohne UL49.5/gM-Komplex. Ähnlich wie bei anderen Alpha-Herpesviren war hier wahrscheinlich der zweite Umhüllungsschritt im Zytoplasma der infizierten Zelle gestört, so dass keine infektiöse Virusnachkommenschaft gebildet wurde. Ein Virus mit Deletionen der Genorte UL49 und gE (BoHV-1-DgEDUL49) zeigte hingegen fast keine Beeinträchtigungen im Hinblick auf die Replikationsfähigkeit. Dagegen war die Ausbreitungsmöglichkeit von Zelle-zu-Zelle (cell-to-cell-spread CTCS) einer solchen Mutante im Vergleich zu den entsprechenden einzel-deletierten Viren erheblich verringert. Da es sich hierbei um eine synergistische Verstärkung gegenüber den Einzelmutanten handelte, wurde geschlussfolgert, dass beide Proteine an derselben Funktionskette des CTCS beteiligt sind. Da die doppelt UL49 und gE deletierte Mutante allerdings weiterhin extrazelluläre, infektiöse Virusnachkommenschaften bildete, ist der CTCS als unabhängige Ausbreitungsform offensichtlich durch andere Funktionen bedingt als der klassische Weg der Virusausschleusung. Hinweise darauf, dass gE auch bei BoHV-1 mit pUL49 interagiert konnten dabei durch Kolokalisationsstudien im Laserscanmikroskop abgeleitet werden. Allerdings ließ keine dieser BoHV-1-Mutanten eine besondere Eignung als Vakzinestamm erkennen. Ein gE und TK doppelt deletiertes Virus zeigte hingegen in vitro kaum veränderte Wachstumseigenschaften verglichen mit dem einfach gEdeletierten Virus. Diese Deletionskombination sollte zudem gegenüber einer Virulenzsteigerung durch Rekombination mit Feldviren unempfindlicher sein, als die derzeit erhältlichen Lebendvakzinen. Zur Steigerung der immunogenen Wirkung des Lebendvirus wurde dieser neue Stamm (BoHV-1DgEDTK) in Kombination mit einem adjuvierenden, nicht viruziden, Blockpolymer eingesetzt. Dieser Ansatz wurde in einem Tierversuch an Kälbern im Vergleich zu der Immunisierung mit dem nicht adjuventierten Lebendvirus getestet. Im Ergebnis dieses Tierversuches schieden die Tiere, welche adjuventiert immunisiert wurden, weniger Virus und zudem für eine kürzere Zeit aus. Dies galt im Vergleich mit den nicht immunisierten Kontrolltieren wie auch im Vergleich mit den Tieren, die allein das Lebendvirus zur Immunisierung appliziert bekommen hatten. Auch die Quantifizierung der neutralisierenden Antikörper verdeutlichte eine gesteigerte Immunogenität der Kombination des doppelt deletierten Lebendvirus mit dem Adjuvants. Die sehr gute Immunitätslage der Tiere nach Impfung führte allerdings nach Belastungsinfektion auch zu einer zeitlich verzögerten Serokonversion im Markertest auf Basis des Nachweises von gE-spezifischen Antikörpern. Auch dies muss als Beleg für die hervorragende, immunisierende Leistung der neuen Präparation angesehen werden, da offensichtlich bei einigen der immunisierten Tiere die Virusreplikation soweit unterdrückt wird, dass keine gEspezifische Antikörperantwort mehr erfolgt. Die vorgestellte Kombination eines genetisch überattenuierten Lebendvirus und die Verstärkung der immunogenen Eigenschaften durch Zusatz eines nicht viruziden, potenten Adjuvants können die Grundlage für eine zukünftige Vakzinestratgie zur Bekämpfung der BoHV-1 oder anderer herpesviraler Infektionskrankheiten bilden.
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