POPULARITY
3 episodes with cd47
4 episodes with cd47
2 episodes with cd47
2 episodes with cd47
2 episodes with cd47
Free course ChatGPT4 in medical writing and editing at learnAMAstyle.com · Nascentmc.com for medical writing assistance for your company.Visit nascentmc.com/podcast for full show notes Boxed Warning for CAR-T Cell Therapy: The FDA mandates a boxed warning on all CAR T-cell therapies due to increased secondary cancer risks, affecting six named treatments. This follows investigations into T-cell malignancies in patients treated with BCMA- or CD19-directed therapies. Manufacturers have 30 days to comply or challenge this requirement, reflecting the FDA's stance that benefits still outweigh risks. Dupilumab for Pediatric EOE: The FDA has approved dupilumab for children aged 1-11 with eosinophilic esophagitis (EoE), expanding from its prior approval for older patients. Dupilumab, targeting interleukin-4 and -13, treats EoE, an allergic inflammation causing symptoms like heartburn and difficulty swallowing. The approval, based on the EoE KIDS trial, marks the first FDA-approved EoE treatment for this age group. Wearable Device for Osteopenia: The FDA has cleared Osteoboost, a wearable belt for treating osteopenia, marking a non-drug medical device approach in this field. Developed by Bone Health Technologies, it uses low-intensity vibrations on the spine and hip, inspired by NASA's bone loss prevention methods. Clinical trials show its effectiveness in maintaining bone health, and it was reviewed under the FDA's De Novo process with Breakthrough Device Designation. BSI-082 IND for Solid and Liquid Tumors: The FDA approved an IND application for BSI-082, a novel antibody targeting SIRPα and β to enhance tumor-associated macrophages' phagocytic activity. Developed by Biosion USA, Inc., BSI-082 covers over 90% of human populations and avoids broad toxicity typical in CD47-targeting therapies. Its in vivo efficacy, especially when combined with other antibodies, shows significant anti-tumor effects in animal models. VCA-894A for Charcot Marie-Tooth: The FDA approved an IND application for VCA-894A by Vanda Pharmaceuticals to treat Charcot-Marie-Tooth disease, axonal, type 2S (CMT2S). VCA-894A, an antisense oligonucleotide, targets the IGHMBP2 gene variant responsible for CMT2S. CMT2S, a rare condition with symptoms like muscle weakness and sensory impairment, currently has no available treatments; this approval represents a significant step in addressing this genetic disorder. Free course on ChatGPT4 for medical writers and editors learnAMAstyle.com
主播：拉帝｜奇妙导演 小红书：拉帝阿葵｜动漫大师因为最近突然意识到我们很多朋友已经很久没有上节目甚至处于断联状态！原本壮大的主播阵容最近也变得形单影只，拉帝决定启动“朋友寻回计划”旨在找回那些散落世界各地的朋友们，聊聊看他们最近在做什么？今天寻回的是大洋彼岸的加州老朋友阿葵，在没有录节目的一年时间里，阿葵经历了加州近几年最难找工作毕业季，也在非盈利社会福利公司找到了新方向，最近还去了西雅图回母校看看，顺便也分享了一些令人窒息的ky直男朋友行为。与此同时，拉帝也久违的给阿葵update了一下在上海熏陶下越来越troll的上海段子，让阿葵大受震撼。这到底是怎么一回事呢！ShowNotes：00:37 为年轻时的前缀感到害羞的动漫大师01:07 朋友寻回计划是什么01:46 拉帝和小语吵架了？07:44 加州今年毕业生真烦恼08:14 加州流浪汉救助非盈利组织17:46 毕业生维持着焦虑20:46 关于回到学校的愿望24:37 take a break看看炖锅里的猪蹄27:07 做独立游戏的愿望！30:16 上海上海上海，一天到晚就知道上海36:07 加州的天气36:32 广州今年的天气，阿葵你懂吗？38:22 北美时尚话题？39:41 唐突聊《逆转裁判》43:09 我想吃刺身！45:14 酒保行动45:36 上海吃饭真的太贵了！46:09 买给我46:47 开始收藏CD47:30 我想买衣服！47:58 我们怎么变成这样了啊！49:12 消费观念，有的人买了上海几套房却没有《潜水员戴夫》49:52 加州好的餐厅记忆，睡了就不饿了53:19 我要vroom vroom开车！54:08 西雅图游记和KY直男1:07:47 想去阿拉斯加啦！1:10:31 Resume里面少了一些纽约和巴黎1:11:19 纽约是拉帝的trolling启蒙1:14:09 收尾，听歌本期背景音乐：downt - 111511宮内優里 - 110228 宮内優里 - 110308 宮内優里 - 110404 宮内優里 - 110427 宮内優里 - 110515 宮内優里 - 110525 宮内優里 - 110620 宮内優里 - 110629 宮内優里 - 110704 宮内優里 - 110819 宮内優里 - 110830 宮内優里 - (やすだけんじ 手紙 remix) 宮内優里 - 111004 宮内優里 - 111020 宮内優里 - 111109 宮内優里 - 101026 downt - AM4：50
Dr. Helen Blau is the Donald E. and Delia B. Baxter Foundation Professor and Director of the Baxter Laboratory for Stem Cell Biology at Stanford University. Dr. Blau's research focuses on the basic molecular mechanisms of stem cells and muscle and their application to aging, regenerative medicine, and disease. Her lab aims to understand and apply biology to improve quality of life, and their current primary focus is on understanding the gerozyme 15-PGDH. She talks about the roles of NSAIDs and CD47 in muscle regeneration. She also discusses growing cultured meat and writing a children's book!
Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world. In recent biopharma news, Bavarian Nordic, a Dutch biotech company, has faced setbacks in its late-stage trials for respiratory syncytial virus (RSV) and COVID-19 vaccines. However, the company's CEO, Paul Chaplin, remains optimistic about the potential of the company in the travel vaccine market. Another development is that Eisai's Alzheimer's drug Leqembi has received approval in Japan and is still undergoing regulatory reviews in other countries. Intercept, a liver drug company, has agreed to a buyout by Alfasigma after failing to secure FDA approval for its research on nonalcoholic steatohepatitis (NASH). Bristol Myers' Opdivo has won a trial supporting its expanded use in lung cancer treatment, and new vaccines for respiratory syncytial virus (RSV) have the potential to be powerful tools, although their rollout poses challenges. In a merger deal worth $3 billion, HealthComp, a private equity-owned health benefits administrator, is set to merge with Virgin Pulse, a digital health and wellness company. The transaction aims to create an integrated platform for employer-sponsored health benefits, with investment firms joining forces for the merger. On the other hand, health insurer Centene is laying off 3% of its workforce due to challenges from Medicaid redeterminations and Medicare Advantage (MA) star ratings. Cano Health has sold its Texas and Nevada centers to a subsidiary of Humana for $67 million due to its worsening liquidity position. Lawmakers in Ohio have proposed minimum nurse-to-patient ratios to address nurse recruitment and retention and improve patient care. Nuance Communications has rolled out an automated clinical documentation tool called DAX Copilot, improving efficiency for healthcare providers.Roche has struck a deal to acquire preclinical RNA medicines from Ionis Pharmaceuticals, focusing on treatments for Alzheimer's and Huntington's diseases. Despite recent setbacks in phase 3 trials for respiratory syncytial virus (RSV) and COVID-19 vaccines, Bavarian Nordic CEO Paul Chaplin remains optimistic about the company's future in the travel vaccine market. ProQR's planned sale of eye drugs to Laboratoires Thea has fallen through due to certain ProQR personnel opting not to work for the French company. John Tsai has been appointed as CEO of UK heart drug startup Forcefield Therapeutics. The FDA staff have expressed "major concerns" with Brainstorm's ALS therapy. Obesity drugs like Ozempic and Wegovy could revolutionize the treatment of obesity and advance the understanding of the condition.Gilead Sciences has announced the discontinuation of a Phase III trial for its anti-CD47 antibody, magrolimab, in acute myeloid leukemia (AML). AbbVie has terminated its contract with Caribou Biosciences for the development of allogeneic CAR-T therapies. Astrazeneca and Bristol Myers Squibb have agreed to participate in the first round of price negotiations under the Medicare drug price negotiation program, despite filing lawsuits challenging the program. Italian pharma company Alfasigma has acquired Intercept Pharmaceuticals in an $800 million cash deal. Alto has reported positive Phase II data for post-traumatic stress disorder. Astellas has withdrawn its lawsuit challenging the inflation reduction act.BioNTech has announced plans to manufacture mRNA vaccines in Africa to address the vulnerability of relying on global supply chains for vaccine production. Proper chemical procurement is emphasized to avoid disruptions in the chemical supply chain for research and development (R&D) and drug manufacturing. AbbVie has terminated its contract with Caribou Biosciences as part of its strategy to cull cancer pipelines. AstraZeneca and Bristol Myers Squibb have reluctantly agreed to participate in the Medicare drug price negotiation program. Immunovant's stock has soared following positive Phase
CD47 is a cell surface protein which is overexpressed in several cancer cells and appears to play an important role... The post The importance of CD47 in MDS and other targets of interest appeared first on VJHemOnc.
CD47 is a cell surface protein which is overexpressed in several cancer cells and appears to play an important role... The post The importance of CD47 in MDS and other targets of interest appeared first on VJHemOnc.
The signal, called CD47, is disrupted in autistic people who have a larger-than-average head. The post Excess of ‘don't eat me' cell signals may drive brain enlargement in autism appeared first on Spectrum | Autism Research News.
The signal, called CD47, is disrupted in autistic people who have a larger-than-average head.
The signal, called CD47, is disrupted in autistic people who have a larger-than-average head.
In this podcast episode, Sarah M. Tinsley, PhD, APRN, AOCN, discusses management strategies for secondary AML and novel therapies currently in clinical trials for AML. Topics include:Liposomal cytarabine plus daunorubicin for secondary AMLAn overview of emerging immune-based strategies for AMLEvidence on immune-based therapies, including agents targeting CD47, TIM3, and bispecific antibodiesPresenter:Sarah M. Tinsley, PhD, APRN, AOCNNurse PractitionerCourtesy Assistant ProfessorDepartment of Malignant HematologyMoffitt Cancer CenterUniversity of South FloridaTampa, Florida
Two CD47 targeting companies announced data updates from their clinical programs: Shattuk Labs and ALX Oncology. Both have suffered major stock price declines and in this episode, I go through the updates and discuss the potential of their molecules moving forward. Biogen cannot catch a break with the latest news continuing to contribute to new stock price lows. However, Medicare is close to announcing their National Coverage Determination (NCD) decision on Aduhelm, which will be a big mover for the stock. Help out the show (or join the discord) by becoming a patron at: https://www.patreon.com/breakingbiotech Follow me on twitter @matthewlepoire Send me an email matthewlepoire@gmail.com www.breakingbiotech.com #breakingbiotech Disclaimer: All opinions expressed by Matt (or his guests) in this podcast are solely his (their) opinions. You should not treat any opinion expressed by Matt in this podcast as a specific inducement to make a particular investment or follow a particular strategy, but only as an expression of his opinion. Matt's opinions are based upon information he considers reliable, but Matt cannot warrant its completeness or accuracy, and it should not be relied upon as such. Matt is not under any obligation to update or correct any information provided in this podcast. Past performance is not indicative of future results. Matt does not guarantee any specific outcome or profit. You should be aware of the real risk of loss in following any strategy or investment discussed in this podcast. #biotech
Trillium Therapeutics is acquired by Pfizer for $2.26B! Finally, the small-mid cap biotech sectors sees good news with M&A activity that rippled through the sector. In this video, I talk about a few other companies that have CD47 assets that should see tailwinds from the TRIL acquisition. I also talk about the recent controversy surrounding Cassava Sciences and the citizen's petition filing with the FDA. A package was provided to the FDA alleging misconduct and requesting a halt on further clinical development of Simufilam. I talk about how we got here and what's next in the saga. The other companies mentioned in this video are $ALXO $STTK $TGTX $CRTX $CYCN $YMTX $ALEC $ANVS $AVXL $APLS Help out the show (or join the discord) by becoming a patron at: https://www.patreon.com/breakingbiotech Follow me on twitter @matthewlepoire Send me an email matthewlepoire@gmail.com www.breakingbiotech.com #breakingbiotech Disclaimer: All opinions expressed by Matt (or his guests) in this podcast are solely his (their) opinions. You should not treat any opinion expressed by Matt in this podcast as a specific inducement to make a particular investment or follow a particular strategy, but only as an expression of his opinion. Matt's opinions are based upon information he considers reliable, but Matt cannot warrant its completeness or accuracy, and it should not be relied upon as such. Matt is not under any obligation to update or correct any information provided in this podcast. Past performance is not indicative of future results. Matt does not guarantee any specific outcome or profit. You should be aware of the real risk of loss in following any strategy or investment discussed in this podcast. #biotech
This week on the podcast Agustin celebrates the acquisition of Trillium Therapeutics, a previous pick of the week, comments on the future acquisition prospects for other CD47 players (i.e. $ALXO/ALX Oncology) within the market, and shares his thoughts on the questionable data behind Cassava Sciences and there dubious efficacy claims. Make sure to like, comment, subscribe and follow me on Twitter @biotech_bros
La Dra. Laura Torrecillas, oncóloga médica adscrita al Centro Médico Nacional "20 de Noviembre", ISSSTE en la Ciudad de México, México, nos habla sobre lo mejor del Congreso de ESMO GI 2021. Cáncer gástrico y de la unión gastroesofágico: KEYNOTE-811: Ensayo fase 3 de pembrolizumab en 1L más el estándar de tratamiento (trastuzumab y quimioterapia; las opciones de quimioterapia son 5-fluoracilo más cisplatino o capecitabina más oxaliplatino) en pacientes con cáncer gástrico o en la unión gastroesofágica metastásico o irresecable, HER2 positivo vs. placebo más trastuzumab y quimioterapia. Destiny: Análisis post-hoc de trastuzumab deruxtecán vs. quimioterapia en pacientes con cáncer gástrico avanzado HER2 positivo, que mostraban progresión en ≥2 líneas previas de tratamiento. SO-31 ASPEN-01: Estudio fase 1 de ALX148, un bloqueador de CD47, en combinación con trastuzumab, ramucirumab y paclitaxel en pacientes con cáncer avanzado de la unión gástrica o gastroesofágica, HER2 positivo, de segunda línea. Análisis sobre el impacto de la quimioterapia adyuvante en pacientes que recibieron como tratamiento neoadyuvante quimioterapia. Cáncer de colon: Análisis sobre el uso excesivo de antibióticos y el impacto que estos tienen en la incidencia de cáncer de colon en pacientes menores a 50 años. REVERCE: Regorafenib seguido de cetuximab vs. la secuencia inversa para pacientes con cáncer colorrectal metastásico. SAPPHIRE: Analiza el mantenimiento de panitumumab en combinación (LV o mFOLFOX) después de una primera línea con mFOLFOX6 + panitumumab, en pacientes RAS wt. Valentino: Mantenimiento basado en panitumumab en pacientes con cáncer colorrectal metastásico, RAS wt. KEYNOTE-177: Estudio aleatorizado, fase III, de pembrolizumab vs. quimioterapia para el cáncer colorrectal avanzado con inestabilidad microsatelital. Entre otros... Cáncer de recto: AVANA: Estudio fase II de quimioterapia más radioterapia preoperatoria más avelumab en pacientes con cáncer de recto localmente avanzado. Averectal: Radiación neoadyuvante de corta duración seguida de mFOLFOX-6 más avelumab para el adenocarcinoma de recto localmente avanzado. Tumores neuroendocrinos: NETTER-1: Lutecio-177-DOTATATE (radiofármaco) en pacientes con tumores neuroendocrinos del intestino medio.
Trillium Therapeutics held its R&D day on April 28th, 2021. There, they presented data updates on the effects of TTI-621 and TT-622 in lymphoma indications. They also announced 7 hematologic and solid tumor indications that they are going to focus on for the next year or so. In this episode, I go through these details and talk about the CD47 space as a whole. I also discuss updates from CYCN and ADVM. Check out our sponsor at Gallant.com and use promo code: BIO to save when you enroll your pet for stem cell banking. Help out the show (or join the discord) by becoming a patron at: https://www.patreon.com/breakingbiotech Follow me on twitter @matthewlepoire Send me an email matthewlepoire@gmail.com www.breakingbiotech.com #breakingbiotech Disclaimer: All opinions expressed by Matt in this podcast are solely his opinions. You should not treat any opinion expressed by Matt in this podcast as a specific inducement to make a particular investment or follow a particular strategy, but only as an expression of his opinion. Matt's opinions are based upon information he considers reliable, but Matt cannot warrant its completeness or accuracy, and it should not be relied upon as such. Matt is not under any obligation to update or correct any information provided in this podcast. Past performance is not indicative of future results. Matt does not guarantee any specific outcome or profit. You should be aware of the real risk of loss in following any strategy or investment discussed in this podcast. #biotech
Featuring an interview with Dr Harry Paul Erba, including the following topics: Improvement in overall survival in the VIALE-A trial with azacitidine/venetoclax compared to azacitidine alone for patients with previously untreated acute myeloid leukemia (AML) ineligible for intensive chemotherapy (0:00) Delay in time to deterioration of health-related quality of life for patients with AML receiving venetoclax in combination with azacitidine or low-dose cytarabine (2:26) Interim analysis of the Phase Ib/II study of venetoclax with FLAG-IDA for patients with newly diagnosed or relapsed/refractory (R/R) AML (4:12) High rates of minimal residual disease-negative complete remission and excellent tolerability with venetoclax added to cladribine and low-dose ara-C alternating with 5-azacitidine for newly diagnosed AML in older patients (7:14) Final results of a Phase III study evaluating CPX-351 versus 7 + 3 for older adults with newly diagnosed high-risk or secondary AML (8:39) Phase II study of CPX-351 with venetoclax for patients with AML (11:07) Results with venetoclax and azacitidine for chemotherapy-ineligible patients with untreated AML with IDH1/2 mutations (18:00) Improvement in overall survival with ivosidenib compared to standard therapies for relapsed or refractory AML with IDH1 mutation (22:26) Beat AML Master Trial: Enasidenib monotherapy with the addition of azacitidine for nonresponders is effective in older patients with newly diagnosed AML with IDH2 mutations (24:48) Efficacy of gilteritinib in patients with R/R AML harboring FLT3 mutations (26:46) Clinical outcomes for patients with R/R AML treated with gilteritinib who received prior midostaurin or sorafenib (30:17) Difference in patterns of secondary resistance between Type I and Type II FLT3 inhibitors in patients with AML (31:33) Final results of a Phase I study of gilteritinib in combination with induction and consolidation chemotherapy for patients with newly diagnosed AML (34:21) Phase III LACEWING study of gilteritinib, gilteritinib with azacitidine or azacitidine alone for patients with newly diagnosed AML with FLT3 mutations who are ineligible for intensive induction chemotherapy (35:28) Efficacy and safety of venetoclax in combination with gilteritinib in patients with R/R AML with FLT3 mutations in the expansion cohort of a Phase Ib study (38:27) Phase Ib results with the first-in-class anti-CD47 antibody magrolimab combined with azacitidine for AML (41:29) Results from the QUAZAR AML-001 maintenance trial of CC-486 for patients with AML (46:00) BMT CTN 1102 trial comparing reduced-intensity allogeneic hematopoietic cell transplantation to hypomethylation therapy or best supportive care for patients aged 50 to 75 with advanced myelodysplastic syndromes (MDS) (51:45) Health-related quality-of-life outcomes for patients with MDS with ring sideroblasts treated with luspatercept in the MEDALIST study (56:52) Interim analysis of the Phase III European SINTRA-REV trial of lenalidomide for patients with low-risk del(5q) MDS who are not transfusion dependent (1:01:26) Safety, efficacy and patient-reported outcomes with venetoclax in combination with azacitidine for patients with higher-risk MDS (1:04:38) Efficacy and safety of pevonedistat and azacitidine compared to azacitidine alone for patients with higher-risk MDS in the Pevonedistat-2001 trial (1:08:53) Conclusions in AML and MDS from 2021 Highlights of ASH® (1:11:19) CME information and select publications
Featuring an interview with Dr Gilles Salles on the following topics: Novel and emerging strategies for diffuse large B-cell lymphoma (DLBCL) (0:00) Available efficacy and safety data with the antibody-drug conjugate polatuzumab vedotin for DLBCL (1:01) Mechanism of action of selinexor, the novel selective inhibitor of nuclear export; key efficacy and safety findings from the pivotal Phase II SADAL trial of selinexor for relapsed/refractory (R/R) DLBCL (8:15) Emerging data with tafasitamab and biologic rationale for combining it with lenalidomide for DLBCL; benefits and risks of tafasitamab/lenalidomide for patients with R/R DLBCL (14:58) Role of chimeric antigen receptor (CAR) T-cell therapies in the management of DLBCL (25:18) Therapeutic algorithm for patients with DLBCL (31:35) Biologic rationale for the investigation of the novel bispecific antibody mosunetuzumab; activity and tolerability of mosunetuzumab in DLBCL (38:46) Efficacy of the antibody-drug conjugate loncastuximab tesirine and the anti-CD47 antibody magrolimab; role of venetoclax-based therapy for DLBCL (45:34) Case: A man in his late 60s with DLBCL receives polatuzumab vedotin in combination with bendamustine/rituximab (B/R) after disease progression on 3 lines of therapy, including autologous stem cell transplant and CAR T-cell therapy (53:30) Sequencing of tafasitamab/lenalidomide, polatuzumab vedotin/BR and selinexor for patients with R/R DLBCL (1:01:32) Response to bispecific antibodies in patients with DLBCL (1:04:59) Case: A woman in her mid-70s receives tafasitamab and lenalidomide after experiencing disease relapse on R-CHOP for Stage IV DLBCL (1:09:22) Case: A man in his early 70s presents with DLBCL with C-MYC and Bcl-2 translocation (1:11:21) CME information and select publications
Go online to PeerView.com/ZAW860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Myelodysplastic syndromes (MDS) are a group of clonal myeloid neoplasms characterized by reduced and/or defective production of red blood cells, platelets, and mature granulocytes, often resulting in anemia, bleeding, increased risk of infection, and risk of transformation to AML. For many years, supportive therapy, blood transfusion, erythropoiesis-stimulating agents, and treatment of infections were the only therapies available. Subsequently, DNA methyltransferase inhibitors and immunomodulators showed survival benefits in MDS, leading to additional research on the efficacy of novel erythroid maturation agents in the setting of MDS-related anemia. Currently, multiple innovative therapies—including multikinase inhibitors, NEDD8-activating enzyme inhibitors, isocitrate dehydrogenase 1/2 inhibitors, BCL-2 inhibitors, and CD47 antibodies—are being investigated to improve care across different MDS populations, including low-, intermediate-, or high-risk patients, elderly individuals with comorbid conditions, and those ineligible for intensive treatment. At a recent CME web broadcast, an expert panel discussed the diagnosis and management of MDS. The panelists reviewed innovative treatment strategies, prognostic scoring systems for risk stratification, and how hematologist-oncologists can recommend appropriate therapeutic options for patients with MDS. Upon completion of this activity, participants should be better able to: Recognize the pathophysiology, clinical features, and modern prognostic scoring system for risk stratification in myelodysplastic syndromes (MDS), Identify mechanisms of action and safety-efficacy data of currently available and novel investigational agents in the settings of low-, intermediate-, and high-risk groups as well as MDS with adverse or targetable genetic features, Select risk-adapted therapeutic strategies for patients with MDS, based on the prognostic scoring systems and baseline factors such as patient age and comorbid conditions, Develop individualized treatment plans based on the potential use of novel and emerging combination therapies for managing high-risk MDS with targetable genetic mutations.
Go online to PeerView.com/ZAW860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Myelodysplastic syndromes (MDS) are a group of clonal myeloid neoplasms characterized by reduced and/or defective production of red blood cells, platelets, and mature granulocytes, often resulting in anemia, bleeding, increased risk of infection, and risk of transformation to AML. For many years, supportive therapy, blood transfusion, erythropoiesis-stimulating agents, and treatment of infections were the only therapies available. Subsequently, DNA methyltransferase inhibitors and immunomodulators showed survival benefits in MDS, leading to additional research on the efficacy of novel erythroid maturation agents in the setting of MDS-related anemia. Currently, multiple innovative therapies—including multikinase inhibitors, NEDD8-activating enzyme inhibitors, isocitrate dehydrogenase 1/2 inhibitors, BCL-2 inhibitors, and CD47 antibodies—are being investigated to improve care across different MDS populations, including low-, intermediate-, or high-risk patients, elderly individuals with comorbid conditions, and those ineligible for intensive treatment. At a recent CME web broadcast, an expert panel discussed the diagnosis and management of MDS. The panelists reviewed innovative treatment strategies, prognostic scoring systems for risk stratification, and how hematologist-oncologists can recommend appropriate therapeutic options for patients with MDS. Upon completion of this activity, participants should be better able to: Recognize the pathophysiology, clinical features, and modern prognostic scoring system for risk stratification in myelodysplastic syndromes (MDS), Identify mechanisms of action and safety-efficacy data of currently available and novel investigational agents in the settings of low-, intermediate-, and high-risk groups as well as MDS with adverse or targetable genetic features, Select risk-adapted therapeutic strategies for patients with MDS, based on the prognostic scoring systems and baseline factors such as patient age and comorbid conditions, Develop individualized treatment plans based on the potential use of novel and emerging combination therapies for managing high-risk MDS with targetable genetic mutations.
Go online to PeerView.com/ZAW860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Myelodysplastic syndromes (MDS) are a group of clonal myeloid neoplasms characterized by reduced and/or defective production of red blood cells, platelets, and mature granulocytes, often resulting in anemia, bleeding, increased risk of infection, and risk of transformation to AML. For many years, supportive therapy, blood transfusion, erythropoiesis-stimulating agents, and treatment of infections were the only therapies available. Subsequently, DNA methyltransferase inhibitors and immunomodulators showed survival benefits in MDS, leading to additional research on the efficacy of novel erythroid maturation agents in the setting of MDS-related anemia. Currently, multiple innovative therapies—including multikinase inhibitors, NEDD8-activating enzyme inhibitors, isocitrate dehydrogenase 1/2 inhibitors, BCL-2 inhibitors, and CD47 antibodies—are being investigated to improve care across different MDS populations, including low-, intermediate-, or high-risk patients, elderly individuals with comorbid conditions, and those ineligible for intensive treatment. At a recent CME web broadcast, an expert panel discussed the diagnosis and management of MDS. The panelists reviewed innovative treatment strategies, prognostic scoring systems for risk stratification, and how hematologist-oncologists can recommend appropriate therapeutic options for patients with MDS. Upon completion of this activity, participants should be better able to: Recognize the pathophysiology, clinical features, and modern prognostic scoring system for risk stratification in myelodysplastic syndromes (MDS), Identify mechanisms of action and safety-efficacy data of currently available and novel investigational agents in the settings of low-, intermediate-, and high-risk groups as well as MDS with adverse or targetable genetic features, Select risk-adapted therapeutic strategies for patients with MDS, based on the prognostic scoring systems and baseline factors such as patient age and comorbid conditions, Develop individualized treatment plans based on the potential use of novel and emerging combination therapies for managing high-risk MDS with targetable genetic mutations.
Go online to PeerView.com/ZAW860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Myelodysplastic syndromes (MDS) are a group of clonal myeloid neoplasms characterized by reduced and/or defective production of red blood cells, platelets, and mature granulocytes, often resulting in anemia, bleeding, increased risk of infection, and risk of transformation to AML. For many years, supportive therapy, blood transfusion, erythropoiesis-stimulating agents, and treatment of infections were the only therapies available. Subsequently, DNA methyltransferase inhibitors and immunomodulators showed survival benefits in MDS, leading to additional research on the efficacy of novel erythroid maturation agents in the setting of MDS-related anemia. Currently, multiple innovative therapies—including multikinase inhibitors, NEDD8-activating enzyme inhibitors, isocitrate dehydrogenase 1/2 inhibitors, BCL-2 inhibitors, and CD47 antibodies—are being investigated to improve care across different MDS populations, including low-, intermediate-, or high-risk patients, elderly individuals with comorbid conditions, and those ineligible for intensive treatment. At a recent CME web broadcast, an expert panel discussed the diagnosis and management of MDS. The panelists reviewed innovative treatment strategies, prognostic scoring systems for risk stratification, and how hematologist-oncologists can recommend appropriate therapeutic options for patients with MDS. Upon completion of this activity, participants should be better able to: Recognize the pathophysiology, clinical features, and modern prognostic scoring system for risk stratification in myelodysplastic syndromes (MDS), Identify mechanisms of action and safety-efficacy data of currently available and novel investigational agents in the settings of low-, intermediate-, and high-risk groups as well as MDS with adverse or targetable genetic features, Select risk-adapted therapeutic strategies for patients with MDS, based on the prognostic scoring systems and baseline factors such as patient age and comorbid conditions, Develop individualized treatment plans based on the potential use of novel and emerging combination therapies for managing high-risk MDS with targetable genetic mutations.
Go online to PeerView.com/ZAW860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Myelodysplastic syndromes (MDS) are a group of clonal myeloid neoplasms characterized by reduced and/or defective production of red blood cells, platelets, and mature granulocytes, often resulting in anemia, bleeding, increased risk of infection, and risk of transformation to AML. For many years, supportive therapy, blood transfusion, erythropoiesis-stimulating agents, and treatment of infections were the only therapies available. Subsequently, DNA methyltransferase inhibitors and immunomodulators showed survival benefits in MDS, leading to additional research on the efficacy of novel erythroid maturation agents in the setting of MDS-related anemia. Currently, multiple innovative therapies—including multikinase inhibitors, NEDD8-activating enzyme inhibitors, isocitrate dehydrogenase 1/2 inhibitors, BCL-2 inhibitors, and CD47 antibodies—are being investigated to improve care across different MDS populations, including low-, intermediate-, or high-risk patients, elderly individuals with comorbid conditions, and those ineligible for intensive treatment. At a recent CME web broadcast, an expert panel discussed the diagnosis and management of MDS. The panelists reviewed innovative treatment strategies, prognostic scoring systems for risk stratification, and how hematologist-oncologists can recommend appropriate therapeutic options for patients with MDS. Upon completion of this activity, participants should be better able to: Recognize the pathophysiology, clinical features, and modern prognostic scoring system for risk stratification in myelodysplastic syndromes (MDS), Identify mechanisms of action and safety-efficacy data of currently available and novel investigational agents in the settings of low-, intermediate-, and high-risk groups as well as MDS with adverse or targetable genetic features, Select risk-adapted therapeutic strategies for patients with MDS, based on the prognostic scoring systems and baseline factors such as patient age and comorbid conditions, Develop individualized treatment plans based on the potential use of novel and emerging combination therapies for managing high-risk MDS with targetable genetic mutations.
Go online to PeerView.com/ZAW860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Myelodysplastic syndromes (MDS) are a group of clonal myeloid neoplasms characterized by reduced and/or defective production of red blood cells, platelets, and mature granulocytes, often resulting in anemia, bleeding, increased risk of infection, and risk of transformation to AML. For many years, supportive therapy, blood transfusion, erythropoiesis-stimulating agents, and treatment of infections were the only therapies available. Subsequently, DNA methyltransferase inhibitors and immunomodulators showed survival benefits in MDS, leading to additional research on the efficacy of novel erythroid maturation agents in the setting of MDS-related anemia. Currently, multiple innovative therapies—including multikinase inhibitors, NEDD8-activating enzyme inhibitors, isocitrate dehydrogenase 1/2 inhibitors, BCL-2 inhibitors, and CD47 antibodies—are being investigated to improve care across different MDS populations, including low-, intermediate-, or high-risk patients, elderly individuals with comorbid conditions, and those ineligible for intensive treatment. At a recent CME web broadcast, an expert panel discussed the diagnosis and management of MDS. The panelists reviewed innovative treatment strategies, prognostic scoring systems for risk stratification, and how hematologist-oncologists can recommend appropriate therapeutic options for patients with MDS. Upon completion of this activity, participants should be better able to: Recognize the pathophysiology, clinical features, and modern prognostic scoring system for risk stratification in myelodysplastic syndromes (MDS), Identify mechanisms of action and safety-efficacy data of currently available and novel investigational agents in the settings of low-, intermediate-, and high-risk groups as well as MDS with adverse or targetable genetic features, Select risk-adapted therapeutic strategies for patients with MDS, based on the prognostic scoring systems and baseline factors such as patient age and comorbid conditions, Develop individualized treatment plans based on the potential use of novel and emerging combination therapies for managing high-risk MDS with targetable genetic mutations.
Hello there! Welcome to the international showcase of writers from all walks of life! Today it’s my pleasure to present poetry by Dr. Thomas Davison. Thank you for sharing your work with us! Dr. Davison is teaching at two all-male prison facilities in Northern Ohio. He has been deeply moved by his interactions with incarcerated students and has been motivated to create poems and short stories about these experiences. Thomas has started a non-profit dedicated to providing free one-on-one support services for felons. You can view more of his published work at: https://thomasdavisoncom.wordpress.com TAKING A WALK IN MY YARD THIS MORNING: The State prison culture is unique. The felons live by their own code and set of values. There is no better place to observe this – then in the prison Yard. The following poem Taking a Walk in My Yard This Morning best captures what it truly feels like – for me. The prison ‘pecking order’ is complex and fluid. As you probably can imagine - there are some very hard people on the inside. The prison Yard is an integral part of prison life. It is the place where reputations are made – and lost. It is where leaders are crowned - and dethroned. It is where all social activities have their origins – and their endings. This is where individuals and gangs have their battles – and wars. Trips to everything important in a felon’s life: visitation, mess hall, chapel, etc., all pass through the Yard. JUST ANOTHER DAY IN MY HOUSE: Like most people I want to believe that I am a good judge of character. I have spent most of my adult life working with young men. In the US Army, with my son’s and grandson’s boy scout troops, with inner city college students, and with incarcerated felons. I also want to believe that I am a realist. There is no doubt that I am an optimist. I’m one of those folks who is always looking for that ‘silver lining’ in any situation. I have been accused of being a Pollyanna. That is not true. I see people for what they are – but – I also see people (especially my students) for their potential - of what they can become. The prison changes all men. For some this change is for the worse. Mental health is a huge challenge within the prisons. The following poem Just Another Day in My House - is my way of accepting that for some - there is not always potential - or a silver lining. For some there is only a slow sinking into the abysmal pit of: self-despair – anger – retribution – and ultimately madness. At the risk of being referred to as ‘Captain Obvious’ – prison has a dark-side. HOLD ON: The first thing that I ever wrote about the state prisons was the following poem called Hold On. The feelings and stress felt by the prisoners is apparent every moment of every day. Half of the prison staff and administration – that I work and talk with - on an almost daily basis – sincerely believe their role is to punish felons for their offenses to society. Whereas, the other half (just as sincerely) believe that it is their role to rehabilitate these offenders. I am reminded of a boat with rowers on both sides. One side is rowing in what they believe is the best direction for their ship. While the other side is rowing just as eagerly to a totally different direction. Result – the ship is going nowhere – it is in the middle of the ocean spinning in tight little circles. Unable to change course. We as an American Society must decide if prisons exist to rehabilitate or to punish. It can’t do both. Previously published works: Taking a Walk in My Yard This Morning – Teach. Write. A Writing Teachers’ Literary Journal Spring/Summer 2020. Just Another Day in My House – Black Petals, Issue #91, Spring, 2020 -- Creative Drive is an international podcast produced by J. Alejandro to bring visibility to poets and writers from all walks of life. Now accepting 3 poems or flash fiction! https://cruzfolio.com/you/ Acepto poesia y relatos cortos en español! https://cruzfolio.com/fuerza-creativa/ For more information about the podcast, visit https://cruzfolio.com/creative-drive-…
CD47 is the latest immuno-oncology target and multiple companies are commercializing molecules in blood and solid tumors. Two exciting companies in the space are Trillium Therapeutics and ALX Oncology. Both of them have molecules that target CD47 to stop the "don't eat me" response from macrophages. However, each therapeutic has some interesting characteristics that will define its efficacy and safety profile. In this video, I contrast the companies and discuss the data to date. If you want to help out the show (or join the discord), become a patron at: https://www.patreon.com/breakingbiotech Follow me on twitter @matthewlepoire Send me an email matthewlepoire@gmail.com www.breakingbiotech.com #breakingbiotech Disclaimer: All opinions expressed by Matt in this podcast are solely his opinions. You should not treat any opinion expressed by Matt in this podcast as a specific inducement to make a particular investment or follow a particular strategy, but only as an expression of his opinion. Matt's opinions are based upon information he considers reliable, but Matt cannot warrant its completeness or accuracy, and it should not be relied upon as such. Matt is not under any obligation to update or correct any information provided in this podcast. Past performance is not indicative of future results. Matt does not guarantee any specific outcome or profit. You should be aware of the real risk of loss in following any strategy or investment discussed in this podcast. #biotech #tril
In this episode, Naval G. Daver, MD, discusses promising investigational agents and treatment combinations in clinical trials for patients with newly diagnosed and relapsed/refractory AML, including:FLT3 inhibitors crenolanib and quizartinibAnti-CD47 antibody magrolimabIMGN632, a CD123 antibody–drug conjugateAnti-CD70 antibody cusatuzumabAPR-246, targeting the TP53 mutationContent is part of an online CME program supported by an educational grant from Daiichi-Sankyo.Link to full program, including a ClinicalThought commentary: https://bit.ly/2Y2uCG2
A special video supplement to a CME conference held during the 61st ASH Annual Meeting featuring expert comments on the management of acute myeloid leukemia. Featuring perspectives from Dr Richard M Stone. Design and results of the QUAZAR AML-001 maintenance trial assessing CC-486 versus placebo for patients with AML in first remission (00:00) Mechanism of action of azacitidine in AML (04:09) Preclinical data on the use of anti-inflammatory agents for clonal hematopoiesis of indeterminate potential (CHIP) (05:56) Ongoing investigations of anti-CD47 antibodies, antibody-drug conjugates and immune checkpoint inhibitors for AML (07:40) Clinical relevance of CHIP mutations (11:05) Pathophysiology of CHIP mutations and cardiovascular disease (16:23) Composition of CPX-351; advantages and disadvantages in the management of AML (17:45) Efficacy and safety of CPX-351 for secondary AML; patient selection for treatment with CPX-351 (20:10) Investigation of venetoclax-based combination strategies in AML (23:27) Factors determining eligibility for intensive chemotherapy for older and younger patients with AML (26:10) Counseling patients on potential outcomes of intensive chemotherapy for AML (30:51) Duration of therapy with an HMA and venetoclax for patients with AML (34:27) Genetic alterations in AML; incidence and biology of FLT3 mutations (36:12) Clinical presentation of patients with AML with FLT3 mutations; activity of the FLT3 inhibitors gilteritinib and midostaurin (38:44) Role of FLT3 inhibitors as a bridge to transplant and in the post-transplant setting (42:12) Tolerability of FLT3 inhibitors for patients with AML and choice of agent in the post-transplant maintenance setting (45:18) Evidence with and ongoing investigation of the FLT3 inhibitor quizartinib in patients with AML with a FLT3 mutation (47:28) Incidence of IDH mutations in AML; treatment for AML with IDH1 and IDH2 mutations (49:45) Differentiation syndrome with IDH inhibitors: Incidence, presentation and management (54:20) Treatment options for patients with AML harboring IDH or FLT3 mutations who are unfit for intensive chemotherapy (57:02) Future developments in the management of AML (59:28) Long-term outcomes with HMA and venetoclax in AML (1:01:32) CME information and select publications
Host: Vincent Racaniello Guests: Nicholas Arpaia and Tal Danino Vincent meets up with Nick and Tal to explain how they engineered E. coli to lyse within tumors and deliver an antibody that causes tumor regression in mice. Links for this episode: Programmable bacteria induce tumor immunity (Nat Med) Synchronized cycles of bacterial lysis (Nature) TWiM Listener survey Subscribe to TWiM (free) on iTunes, Google Podcasts, Stitcher, Android, RSS, or by email. You can also listen on your mobile device with the Microbeworld app. Become a Patron of TWiM! Music used on TWiM is composed and performed by Ronald Jenkees and used with permission. Send your microbiology questions and comments to twim@microbe.tv
ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer. 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. The 2019 ASCO Annual Meeting, held May 31 to June 4, brought together physicians, researchers, patient advocates, and other health care professionals from around the world to present and discuss the latest research in cancer treatment and patient care. In the annual Research Round Up podcast series, Cancer.Net Associate Editors share their thoughts on the most exciting scientific research to come out of this year’s ASCO Annual Meeting and what it means for patients. First, Dr. Jeffrey Meyerhardt will discuss 4 studies in gastrointestinal cancers, including 1 on colorectal cancer, 1 on gastric cancer, and two studies related to pancreatic cancer. Dr. Meyerhardt is the Douglas Gray Woodruff Chair in Colorectal Cancer Research, Clinical Director and Senior Physician at the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute, Deputy Clinical Research Officer at the Dana-Farber Cancer Institute, and Professor of Medicine at Harvard Medical School. He is also the Cancer.Net Associate Editor for gastrointestinal cancers. Dr. Meyerhardt: My name's Jeff Meyerhardt. I'm a gastrointestinal medical oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts. Today I'm going to discuss research on gastrointestinal cancers that were presented at the 2019 ASCO Annual Meeting. And let's talk about four studies: 1 in colon cancer, 1 in gastric cancer, and 2 studies related to pancreatic cancer, all of which are going to affect how patients are treated in the upcoming years. Starting with the studies on colon cancer, there were 2 additional studies looking at the duration of adjuvant therapy for colon cancer. Adjuvant therapy is the chemotherapy that's given after surgery for people who had a resection of their colon cancer that didn't have evidence of metastases. We give adjuvant therapy to try to prevent and reduce the risk of recurrent disease. The standard of care up till a few years ago was to give 6 months of adjuvant therapy. And for most patients who had stage III or lymph node positive disease, that was 6 months of a fluoropyrimidine, either 5-FU, or an oral form capecitabine with oxaliplatin. This was also given to some patients who have higher-risk stage II disease. Two years ago at ASCO, we learned that giving 3 months of therapy was sufficient, or what we'd describe as non-inferior, for some patients who have stage III colon cancer, particularly those who had what would be considered a better-risk stage II colon cancer, and actually particularly if they got a particular regimen of combining capecitabine and oxaliplatin. At this year's ASCO, there was a study looking at patients with stage II disease. Most of them had higher-risk stage II disease, something where they didn't have positive lymph nodes, but some other feature that made you a little bit more worried that there was a relatively higher-risk of recurrent disease. And the findings were essentially very similar to what we saw for stage III disease; that for some patients, 3 months of treatment was adequate, particularly if you gave capecitabine/oxaliplatin, and had less toxicity than 6 months of therapy. But if you gave 5-FU/leucovorin/oxaliplatin, a regimen called FOLFOX, 6 months of treatment was necessary. These studies add to the conclusion that first, we can't treat all colon cancers in the adjuvant setting the same, that we should think of them as risk adjustment, and we also have to make decisions regarding what type of treatment, which will help determine the duration of therapy. The next study I'm going to focus on is looking at gastric cancer and looking specifically at the role of immunotherapy. So what we've already known is that patients who have gastric cancer and esophageal cancer can benefit from immunotherapy in later-line therapy, so after an initial first-line or second-line chemotherapy is no longer helping a patient or is too toxic to continue. The study that was presented at ASCO this year, what is called the KEYNOTE-062 study, was actually looking at 3 different arms of therapy. One was giving a drug pembrolizumab, one of the immunotherapies alone. The second arm was giving chemotherapy alone. And the third arm was giving pembrolizumab with chemotherapy. In looking at what would be the best strategy for patients who are initially being treated for metastatic gastric cancer. They specifically looked at patients where we think there may be a higher chance of activity. So there are certain ways to look at the tumor and score what's the potential in immunotherapy would be helpful. And this is what's called the CPS score. Patients who had had a CPS score of at least 1, and they also broke it down for people that had even a higher score, greater than 10, in the analysis. And what they found is compared to doing standard chemotherapy, in this case, of fluoropyrimidine, 5-FU, or capecitabine with a platinum, cisplatin, giving pembrolizumab could be non-inferior in terms of overall survival for patients as initial therapy for metastatic gastric cancer; that they saw that in patients who had a CPS score greater than 1. They showed actually that it was superior to give pembrolizumab in terms of overall survival if the CPS score was greater than 10. What is a little curious in this study is that progression-free survival, which is how long it takes until you have to switch to therapy, wasn't actually better with pembrolizumab compared to chemotherapy for the people who had relatively lower CPS scores. But it was non-inferior for those who had a greater than 10. The second part of the study was looking at should we give chemotherapy and pembrolizumab at the same time, like the whole kitchen sink, at the same time of both giving chemotherapy and an immunotherapy. And that actually didn't add any benefit to chemotherapy alone. So it was not improvement in overall or progression-free survival. So what do we conclude from KEYNOTE-062? Well first is that there are some patients where giving an immunotherapy upfront by itself can be just as good as starting chemotherapy, particularly those who have a score that's a relatively higher likelihood of benefiting from immunotherapy. But we also learned that combining them together does not add extra bang for the buck as initial treatment. There should still be a therapy considered later, whether you start with pembrolizumab and then later get chemotherapy or vice versa. But doing them all at the beginning does not seem to add additional benefits. There were then 2 studies of note for pancreatic cancer. One of them was an adjuvant study, which again, adjuvant therapy is giving chemotherapy after surgery to try to reduce the risk of recurrent disease. What we know for pancreas cancer, there are several options to consider in terms of adjuvant therapy after surgery. For quite a few years now, the standard was giving a drug called gemcitabine. There was then a study looking at gemcitabine with an oral drug called capecitabine, again, the oral form of 5-FU, and that looked to be a little better than gemcitabine alone. And then several years, a study from the Canadian Cancer Treatment Group and then a Unicancer GI PRODIGE Group looked at a combination of folfirinox, a 4-drug regimen that's now very standard for some patients with metastatic pancreas cancer. In looking at that regimen as adjuvant therapy, compared to gemcitabine alone, that study showed a real significant improvement in terms of recurrence rate and disease-free survival for patients who got this 4-drug regimen compared to gemcitabine alone, and has really become a standard for patients who have a good performance status after their surgery. The current study that was presented at the 2019 ASCO Meeting was looking at a different combination, looking at gemcitabine plus another drug called nab-paclitaxel. It's a combination also used in metastatic pancreatic cancer. It was shown to be better than gemcitabine by itself in metastatic pancreatic cancer. And the hope would be another option for patients in the adjuvant setting. Unfortunately, the study fell a little short in terms of the primary endpoint as initially determined when the protocol was being developed, what was called an independent assessment of disease-free survival. So sending the scans and sending all the data to independent reviewers, and that again just fell a little short statistically. If you look at investigator-assessed disease-free survival, it actually was statistically significant, as well as overall survival. The conclusion for the study is even though it didn't quite meet the mark in terms of what was predefined, it does give suggestion that it is better than giving gemcitabine alone. And there are patients in the adjuvant setting for pancreas cancer where folfirinox is probably not as good of an option: it's a fairly toxic regimen. People who have a performance status having a little more difficulty recovering from the surgery or have more comorbidities, gemcitabine plus nab-paclitaxel probably still should be considered an option for these patients, compared to gemcitabine alone. The final study, which led to a plenary session, which is basically one of the 4 most attractive abstracts in the 2019 ASCO Annual Meeting this year, was looking at maintenance therapy for people with metastatic pancreatic cancer using what's called a PARP inhibitor olaparib. It was specifically for patients who had received a platinum-based chemotherapy and they had a germline mutation of BRCA. So BRCA mutations are commonly known to affect the risk of developing breast and ovarian cancer. There are 2: BRCA 1 and BRCA 2. Those also have association with increased risk of pancreatic cancer. And what we know is the PARP inhibitor, through what are called DNA repair mechanism, do seem to have activity in these various type of cancers, including for patients with metastatic pancreatic cancer. This was specifically looking at people who had metastatic pancreatic cancer. Could you get them off the more cytotoxic chemotherapy for a period of time to do something more of what would be considered a maintenance therapy. So having them for period time off toxic therapy and not impacting their overall outcome. It ends up about 4 to 7 percent of metastatic pancreatic cancer patients harbor a BRCA mutation. What we know about BRCA-mutated pancreatic cancers, they have an increased benefit from a platinum-based chemotherapy, cisplatin or oxaliplatin, so patients had to have had a platinum-based therapy to go on the study. They were on chemotherapy for at least 16 weeks and then they were randomized to stop their chemotherapy and receive elaborate versus placebo until there was disease-free, disease progression, or increased toxicity. And what we saw is that the progression-free survival, the time till they had to restart chemotherapy, actually was doubled with the group receiving the maintenance therapy with olaparib. So that was really an exciting finding and a really important finding where you can get people off of chemotherapy for a period of time until you have to restart chemotherapy. Now there is not a survival benefit that was noted yet on the study. It is still very early to look at overall survival. There are also patients who are able to crossover in terms they got olaparib, another part in their cancer treatment, because of the known benefit in metastatic disease. So overall survival may be a little harder to fully interpret, but I do think that this will become a standard for patients with BRCA-mutated colorectal cancers, to receive chemotherapy for some period of time, several months, and then if they're doing well, then to switch them to a maintenance therapy. So that is our summary of the GI cancer research from the 2019 ASCO Annual Meeting. Again, my name is Jeffrey Meyerhardt, and thank you for listening. ASCO: Thank you, Dr. Meyerhardt. Next, Dr. Guillermo Garcia-Manero will discuss a study on a new immunotherapy drug that offers promising results in patients with acute myeloid leukemia or myelodysplastic syndromes, as well as 2 additional studies that looked at t-cell therapies. Dr. Garcia-Manero is the Deputy Chair of Translational Research and Professor, Department of Leukemia, at The University of Texas MD Anderson Cancer Center in Houston, Texas, and the Chief of the Section of Myelodysplastic Syndromes at MD Anderson Cancer Center. He is also the Cancer.Net Associate Editor for Leukemia. Dr. Garcia-Manero: Hello. I am Guillermo Garcia-Manero. I am a professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center. I'm very happy to summarize some of the key presentations at this year's ASCO meeting in Chicago. Of course, ASCO is big on solid tumor malignancies, but there is more and more information regarding leukemia treatment for our patients, also, at the meeting. This year, there were a number of very interesting presentations. First, I want to start briefly saying that there was a very interesting educational symposium where Drs. Al-Kali, Sekeres, Craddock, and myself discussed how to use these hypomethylating agents, drugs like azacitidine or decitabine in patients with leukemia. This meeting was very well attended by multiple community physicians that attend ASCO, and it contained, I think, very useful information in terms of the use of these compounds for our patients. In terms of research presentations, there were multiple. The one that I actually felt was perhaps more interesting was a presentation by Dr. Sallman from the Moffitt Cancer Center in Tampa where he was describing the first results of a new therapy for patients with MDS and AML and potentially other hematological malignancies and cancers known as Hu5F9-G4. This agent is an antibody that targets a molecule called CD47. This was discovered by Dr. Maute and Dr. Weissman at Stanford. It is known to be a “don’t eat me” signal in a way kind of an alternative immune checkpoint inhibitor type of process. But this is interesting because it's focusing more around macrophages more than lymphocytes and it could have a broad use, again, not only in leukemia and hematological malignancies but potentially many other cancers. I think that this data is very striking because the results of Dr. Sallman indicate a very high level of activity with the combination of the hypomethylating agent azacitidine, in this case, both in MDS and AML. This was agnostic of molecular and cytogenetic alterations. It was well tolerated, although there was a little bit of anemia early on with administration of this therapy. But I think this was one of the most innovative and promising new potential therapies for our patients with leukemia. This drug has been shown to be active in lymphoma and now, we expect that the studies initially done in the UK and in Tampa are going to be expanded to other centers in North America, and they may actually provide with a very interesting innovative and very active new form of therapy for our patients. So I thought that was the most innovative presentation at the ASCO meeting. Of course, there were multiple other presentations. There was additional data on new FLT3 inhibitor known as gilteritinib. This drug recently approved for patients with AML. There was also further information on a new compound known as CX-01 for patients with acute myelogenous leukemia. Again, this is an interesting compound that seems to be a heparin analog, and the early studies are showing significant activity as well for our patients. There was also very interesting data in terms of the phase I results of the ZUMA-3 trial. This is a CAR T-cell type of approach for refractory patients with acute lymphocytic leukemia. And finally, this interesting presentation from the MD Anderson group with an off-the-shelf viral-specific T-cell therapy against patients with adenovirus disease that are immunosuppressed. It's actually very important in a way-- kind of similar therapies for patients that have viral complications, this group have shown, actually, significant activity of similar type of approaches for patients with BK virus and other conditions. So in summary, I think that the meeting was very important like it is every year. I think that we're starting to see presentations at ASCO for new agents of high relevance. I think that the community, at least in MDS and AML, it is very interested on the follow-up with the Hu5F9-G4 agent in combination with AZA for MDS and AML. And we're looking forward to be part and see the results of expanded phase II and potential phase III studies with this compound. And with that, I want to thank you for your attention. ASCO: Thank you Dr. Garcia-Manero. Learn more about these topics and other research presented at the 2019 ASCO Annual Meeting at www.cancer.net, including additional Research Round Up podcasts. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. This Cancer.Net podcast is part of the ASCO Podcast Network, a collection of 9 programs covering a range of educational and scientific content offering insight into the world of cancer care. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.
The immunophiles explain how metabolic rewiring of macrophages by CpG promotes clearance of cancer cells. Hosts: Vincent Racaniello, Stephanie Langel, and Cynthia Leifer Become a patron of Immune! Links for this episode Darwin Day Metabolic rewiring of macrophages by CpG (Nat Immunol) Letters read on Immune 17 Time stamps by Jolene. Thanks! Weekly Science Picks Steph- Pregnant Scholar Cindy- Anti-vaxxers vaccinating against measles Vincent- Center for Science in the Public Interest Music by Steve Neal. Immune logo image by Blausen Medical. Send your immunology questions and comments to immune@microbe.tv
Continuing education episode! Ever since the introduction of anti-CD38 (daratumumab, or DARA), blood bankers have been hearing about a new chemotherapy agent, anti-CD47, that would interfere far more in our testing than anti-CD38. Well, anti-CD47 is here (in trials), and it lives up to its reputation! Connie Westhoff and her team report on results from blood bank testing of patients taking the drug, and what you can do to overcome the problems. This episode is eligible for free CME and SAMs/CC credit for physicians and P.A.C.E. contact hours for laboratorians through Transfusion News Continuing Education on Wiley Health Learning.
Regenerative Medicine Today welcomes Dr. Jeffrey Isenberg. Dr. Isenberg is an Associate Professor in the Department of Medicine at the University of Pittsburgh. Dr. Isenberg discusses his research on controlling blood flow and tissue survival, particularly the thrombospondin-1-CD47 signaling nexus. Host John Murphy. For more information about the McGowan Institute for Regenerative Medicine, visit: McGowan Institute [...]
Zymeworks, ProMetic Life Sciences, Innovative Targeting Solutions all back in the news again; Saskatchewan researchers make a breakthrough on a devastating pig virus, and healthcare behemoth GE partners with STEMCELL Technologies.We have this and more on this week’s Biotechnology Focus Podcast! Welcome to Biotechnology Focus Podcast. I’m your host Shawn Lawrence. Story 1 We kick things off this week in the prairies, where in less than a year, University of Saskatchewan (U of S) scientists have developed and tested a prototype vaccine that could protect the North American swine industry from a virus that has killed more than eight million pigs and cost more than $400 million in lost income since 2013. The Porcine Epidemic Diarrhea Virus (PEDV) hit the U.S. in 2013 and spread to Canada in 2014. It is a coronavirus, a virus group which includes important emerging human diseases such as SARS and MERS. It was first discovered in Europe, and has become increasingly problematic in Asian countries. Occurring only in pigs, PEDV can kill up to 100 per cent of infected piglets. Using its new containment Level 3 facility, the Universtiy of Saskatchewan Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac) quickly launched a vaccine development project. The project has resulted in a prototype vaccine that protects 100 per cent of the piglets who have received it, according to Dr. Volker Gerdts, VIDO-InterVac’s research director. The successful vaccine results have since triggered the interest of several animal health companies including Huvepharma, which has partnered with VIDO-InterVac to develop the technology for commercial production in North America. With the support of the swine industry, the vaccine is now undergoing field testing in Saskatchewan, as well as in Manitoba where it is being used to help protect piglets from a recent PEDV outbreak. VIDO-InterVac director Andrew Potter said such a project wouldn’t be possible without this facility, adding that “This is a perfect example of why InterVac was constructed – it is one of the only facilities available internationally with the capacity to conduct vaccine development and testing on this scale for emerging infectious diseases and It helps Canada remain prepared to quickly respond to outbreaks like this,” he said. The PEDV vaccine development project has been supported by a variety of funders including the Government of Saskatchewan (ADF), Sask Pork, and the Canadian Swine Health Network. Story 2 The US Food and Drug Administration (FDA) has given Toronto’s Trillium Therapeutics Inc. the go-ahead to initiate a Phase 1 clinical trial for its lead drug candidate, TTI-621 (SIRPaFc), in solid tumours and mycosis fungoides. Trillium is developing TTI-621 as a novel checkpoint inhibitor of the innate immune system, and the drug is currently being evaluated in an ongoing Phase 1 dose escalation study in patients with relapsed or refractory hematologic malignancies. Patient enrollment in the Phase 1 trial is anticipated to commence by year end. The trial will be multicenter and open-label, with TTI-621 being delivered to patients with relapsed and refractory, percutaneously-accessible cancers by intratumoral injection that increase in dose and dosing frequency to characterize safety, pharmacokinetics, pharmacodynamics and preliminary evidence of antitumour activity. In addition, detailed evaluation of serial, on-treatment tumor biopsies of both injected and non-injected cancer lesions will help characterize tumor microenvironment changes anticipated with CD47 blockade. Story 3 As part of its strategy to leverage and attract investor interest to Québec’s life sciences sector, the Fonds de solidarité FTQ has made a $15 million investment in Genesys Capital’s latest venture fund Genesys Ventures III. The fund itself will used to back companies at the seed-stage, considered by many in the industry the valley of death, to help these companies advance technologies and products for unmet medical needs. Genesys Capital is one of the largest Canadian-based venture capital firms exclusively focused on the life sciences industry. Of note, Knight Therapeutics Inc., a specialized biopharmaceutical company based in Montreal, QC is also committing $1 million to Canadian-based life sciences venture capital fund Genesys Ventures III LP. For Knight the investment is the eighth life sciences equity fund investment Knight has made to date, having committed over $125 million. In terms of the Genesys Ventures III fund, Genesys Capital says it has closed $90 million of its $125 million target for the fund, while Managing director Damian Lamb adds that the firm expects to reach its goal for Genesys Ventures III early next year. Should the fund reach this target, it would be the largest Genesys has raised in its 16-year history. Story 4 Zymeworks is back in the news this week as the United States Food and Drug Administration (FDA) has accepted the company’s Investigational New Drug (IND) application for its lead product ZW25 as a treatment for certain HER2-expressing cancers. ZW25 is a novel bi-specific antibody, developed using the company’s Azymetric™ platform, to target two different epitopes (bi-paratopic targeting) of the human epidermal growth factor receptor 2 (HER2) proteinThe protein is known to be over-expressed on the surface of many tumour types, including certain breast, gastric, lung, and ovarian cancers. ZW25 will be evaluated in the clinic for safety as well as efficacy in patients with tumours with low to moderate levels of HER2 expression. The company anticipates it will begin a Phase 1 clinical trial for ZW25 in late August of this year. Additionally, last week the FDA granted Orphan Drug Designation to ZW25 and a second product, ZW33 for the treatment of ovarian cancer. ZW33 is a drug-conjugated version of ZW25 that is currently in development in preparation for an IND filing in early 2017. Orphan designation qualifies Zymeworks for a number of development incentives, including tax credits for clinical testing and marketing exclusivity for a period of seven years if ZW25 and/or ZW33 is approved for this indication. Story 5 The Ontario Institute for Cancer Research (OICR), Thermo Fisher Scientific and Queen’s University are collaborating on a research study to help bring more targeted diagnosis and treatment to breast cancer patients in the future. The study, led by Dr. John Bartlett, director of OICR’s Transformative Pathology Program, and Dr. Harriet Feilotter, Department of Pathology and Molecular Medicine, Queen’s University, aims to identify mutations and copy number changes found in breast cancer samples and establish whether these abnormalities correlate with on-market drugs, available clinical trials or published studies. OICR-affiliated researchers and collaborators at Queen’s University and Sunnybrook Health Sciences Centre will process the same breast cancer samples to establish whether the results are reproducible at different sites. This study will also characterize more than 400 additional retrospective breast cancer samples supporting ongoing clinical research efforts of Dr. Bartlett’s team at OICR, which strives to improve the clinical management of the disease. Collaborators Drs. Martin Yaffe and Arun Seth at Sunnybrook Health Sciences Centre will provide laboratory space and additional technical support for the study. Dr. Yaffe is also co-leader of OICR’s Smarter Imaging and Imaging Translation Programs. The study will use Thermo Fisher’s Oncomine Comprehensive Assay, a targeted, next-generation sequencing (NGS) research tool that analyzes 143 genes relevant to cancer and which is the NGS assay used for the NCI-MATCH study in the United States. The data generated can be further studied with the Oncomine Knowledgebase Reporter, which is a curated set of published evidence that matches driver genetic variants with relevant information, such as on-market drugs, available clinical trials, or published studies. The findings of the OICR study will be used to assess the technology and could inform subsequent clinical trials. Drs. Feilotter and Bartlett have also engaged six laboratories in Ontario, including at Hamilton Health Sciences, London Health Sciences Centre, Ottawa General Hospital, Sunnybrook Health Sciences Centre, Sudbury Health Science North and University Health Network to look at the robustness and reproducibility of the assay across different cancer samples. This collaboration could extend the findings of this study beyond breast cancer to other common cancers. Story 6 Vancouver’s Innovative Targeting Solutions has teamed up with yet another major life science company, this time striking a research collaboration deal with Janssen Biotech, Inc. (Janssen), through Johnson & Johnson Innovation. The deal will allow Janssen to utilize Innovative Targeting Solutions' proprietary HuTARG™ research platform to discover antibody candidates useful for modulating immune responses in autoimmunity or cancer. The HuTARG™ protein engineering platform is able to engineer both T-cell receptors and fully human antibodies that bind major histocompatibility complex (MHC)/peptide complexes displaying fragments of intracellular proteins of interest. Essentially, it allows researchers to generate and engineer fully human antibodies. The technology underlying the platform is based upon the natural process of V(D)J recombination, employed by the human immune system to produce a diverse repertoire of antibodies. Details of the collaboration including the specific targets, number of targets, and specific therapeutic indications have not yet been disclosed nor have financial details. In June, ITS announced a research collaboration with Merck, to utilize the HuTARG™ research platform to help identify and develop biologic therapeutic candidates directed towards targets that have historically been a challenge for biologic therapies, and just two weeks ago, ITS also partnered with another Vancouver-based company known for its own string of deals with pharma, Zymeworks. Other disclosed ITS collaborators include Novartis and Amgen. Story 7 A few months ago, Biotechnology Focus spoke with Phil Vanek (of GE Healthcare) and Michael May (of CCRM) about BridGE@CCRM, the centre they co-created at the MaRS West Towere to help accelerate the creation of cellular therapeutic tools. Now GE is taking another step in its mission to bring the right infrastructure to the global cell therapy industry, with another unique partnership here in Canada, signing an exclusive licensing agreement with Vancouver-based STEMCELL Technologies Inc., to develop and commercialize cGMP grade versions of STEMCELL’s T-Cell reagents for the isolation, activation, and culture of T-cells in clinical applications. Both parties say these reagents are critical tools in the development and manufacturing of cell and gene therapies intended for administration to patients. The following proprietary reagents from STEMCELL Technologies will be qualified as cGMP-grade materials and licensed by GE Healthcare: ImmunoCult™ Human CD3/CD28 T-Cell Activator, ImmunoCult™ Human CD3/CD28/CD2 T-Cell Activator, EasySep™ Release Human CD3 Positive Selection Kit and the ImmunoCult™–XF T-Cell Expansion Medium. According to Allen Eaves, president and CEO of STEMCELL Technologies Inc. this partnership with GE will give STI customers the confidence of a path to the clinic with a suite of critical cGMP grade T-cell reagents as well as help the industry evolve and make these promising therapies, such as CAR-T cells and TCR-engineered T cells, a clinical reality. The agreement closely follows GE’s acquisition of Biosafe Group SA, as well as many other investments in the space to make available a turnkey, scalable, flexible manufacturing solution that will enable access to these critical therapies. With that we’ve come to the end of this week’s program. We hope you enjoyed it. A big thanks to our production manager Laskey Hart and the rest of the Biotechnology Focus team. You can find past episodes online at www.biotechnologyfocus.ca and we’re always looking for your feedback, story ideas and suggestions so we’d love to hear from you. Simply reach out to us on twitter: @BiotechFocus or by email biotechnology_focus@promotive.net. For all of us here at Biotechnology Focus, thank you for listening.
Anaemia, CD47, HeLa cell lines and cancer. Plus Neem, the planet Pleiades, gastric bands and valium, valium, valium, valium, valium, valium, valium, valium. It’s what you’ll need to get through this episode of Skeptics with a K.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 01/06
The SIRPs are a recently discovered family of glycoproteins comprising more than 30 members belonging to the immunoglobulin superfamily. The two different structural subtypes, termed SIRP α and SIRP β, are distinguished by the presence or absence of a cytoplasmic domain, respectively. SIRP α1, the first member of the family to be purified, had been characterised as a negative regulator of signal transduction, and transformation assays had suggested that it also had tumour suppressive effects. Little or nothing is known about the possible function of either the other SIRP α homologues or the members of the SIRP β subtype. The Ig-like domains possessed in the extracellular domains of all SIRPs suggest they have binding partners outside the cell. Cell adhesion experiments using the extracellular domains of SIRP family members showed that SIRP α have adhesion molecule properties. This led to the identification of CD47 as one ligand for SIRP α, performed in collaboration with others21and confirmed here. Furthermore, these experiments suggested that SIRP α molecules have at least one further unknown ligand that is not CD47. The discovery that SIRP α was a cell adhesion molecule with a regulatory role in signal transduction was expanded by in vitro kinase experiments and experiments with inhibitors of tyrosine kinases. They showed that SIRP α associated with more than one kinase activity, and that cytosolic tyrosine kinases, probably of the srcfamily, were necessary for SIRP α to regulate tyrosine phosphorylation of a receptor. In contrast to SIRP α molecules, proteins belonging to the SIRP β subtype remain uncharacterised. Therefore a large part of this work concentrates on the SIRP β subtype, its associated proteins, localisation and possible function in a cell. In vitro association experiments revealed that SIRP β is part of a multiprotein complex at the cell membrane, where SIRP β1 interacted with DAP12, an adaptor protein with a transmembrane domain. DAP12 linked SIRP β to a cytosolic tyrosine kinase identified as Syk confirmed by western blot and PCR from cDNA preparations of the cell lines used in these experiments. The interaction of Syk with the complex required the tyrosine phosphorylation of DAP12. Coligating SIRP β molecules at the membrane with a SIRP β-specific monoclonal antibody recruited Syk to DAP12 where it could be activated by treatment with sodium pervanadate. In vitro kinase assays detected several unknown phosphorylated proteins associated with SIRP β/DAP12/Syk when Syk was activated that may represent signalling molecules operating downstream of the complex. Cotransfection experiments showed that SIRP α complexed with kinase activities that enabled it to inhibit both DAP12 tyrosine phosphorylation and Syk kinase activity. This suggested that both complexes at some point operated in close contact, so experiments were carried out to localise SIRP proteins in the cell. Fractionation experiments discovered that SIRP α and possibly SIRP β could be detected in fractions that contained GPI microdomains, or caveolae. Similar investigations with the SIRP β1/DAP12 complex revealed that DAP12 was dependent upon SIRP β for its direction to the plasma membrane where it was activated by tyrosine kinases. Membrane localisation of SIRP β was similarly reliant upon DAP12 expression, however, further experiments suggested that SIRP β may be secreted from the cell in the absence of DAP12. To address the potential role of SIRP β1/DAP12 complex in signal transduction, cell lines overexpressing SIRP β and DAP12 were analysed. Cell death assays suggested that the SIRP β1/DAP12 complex was a negative regulator of induced cell death, and that tyrosine kinases might be involved in this regulation. Cells overexpressing SIRP β and DAP12 showed an enhanced rate of acid production, corresponding to an enhanced rate of glucose metabolism. These observations suggests that, SIRP β1/DAP12 overexpression may be a factor that contributing to a transformed phenotype, works in opposition to SIRP α molecules. This work views the SIRPs as components of a cluster of different proteins at the cell membrane that recruit and use other cytosolic proteins, among them tyrosine kinases and phosphatases. It shows that SIRP α molecules may collaborate with SIRP β family members to modulate the signals generated by other receptors in signal transduction. This modulation may influence aberrant cellular processes that lead to disease.
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