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CardioNerds Co-Founder Dr. Daniel Ambinder, Episode Chair Dr. Dinu Balanescu, and FIT Lead Dr. Natalie Tapaskar discuss advanced heart failure in CardioOncology with expert Dr. Richard Cheng. Audio editing by CardioNerds Academy Intern, Dr. Akiva Rosenzveig. In this episode, we discuss the spectrum of advanced heart failure in patients with a history of cancer. We dissect cancer therapy-related cardiac dysfunction (CTRCD) cases and the imaging and biomarker tools available for risk stratification and disease monitoring. We delve into the data on the use of guideline-directed medical therapy (GDMT) and cardiac resynchronization therapy (CRT) in these patients. We discuss the risk of prior radiation and chemotherapy during cardiac surgery. Finally, we learn about the post-transplant risk of rejection, recurrent malignancy, and de-novo malignancies, as well as treatment strategies we can employ for these patients. This episode is supported by a grant from Pfizer Inc. This CardioNerds Cardio-Oncology series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Giselle Suero Abreu, Dr. Dinu Balanescu, and Dr. Teodora Donisan. CardioNerds Cardio-Oncology PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls and Quotes - Advanced Heart Failure in CardioOncology Use the HFA-ICOS risk tool to understand the baseline risk of developing cancer therapy-related cardiac dysfunction (CTRCD). Key factors are type of cancer therapy, baseline CV risk factors, and age. A relative change in global longitudinal strain of more than 15% from baseline is a marker of early cardiac dysfunction and predicts the subsequent risk for systolic dysfunction in patients undergoing cardiotoxic chemotherapy. Statins may be useful in prevention of cardiovascular dysfunction in patients receiving anthracycline chemotherapy. There is limited data on the 4 pillars of GDMT in prevention of CTRCD, but should be started early once CRTCD is suspected or diagnosed! Mediastinal radiation causes adhesions and scarring which increase the risk of bleeding during cardiac surgery, lead to longer operative times, and can lead to RV failure and poor wound healing. Patients with a pre-transplant history of malignancy have a higher risk of mortality due to post-transplant malignancy. And patients with active cancer should not be considered for heart transplant. Post-transplant malignancy risk can be mitigated by utilizing an mTOR based, CNI free immunosuppression regimen. Show notes - Advanced Heart Failure in CardioOncology How do cardio-oncology and advanced heart failure intersect? There are 3 basic populations of patients to consider:Patients with advanced heart failure who develop cancer.Patients with pre-existing chemotherapy and radiation exposure for cancer treatment who later develop advanced heart failureHeart transplant recipients who, in the long term are at very high risk of developing cancer Cardio-oncologists must consider risk assessment and mitigation, long-term prognosis, and treatment strategies for each of these unique populations. How can we assess the risk of developing cardiovascular disease during cancer treatment (CTRCD)? There are many proposed risk tools. However, the majority are not well-validated. One of the most used tools is the HFA-ICOS risk tool.1You can select the planned cancer therapy for the patient (anthracyclines, HER-2, VEGF, RAF/MEK inhibitors, Kinase inhibitors, multiple myeloma therapies) and then calculate their risk of developing CV disease during cancer treatment based on baseline variables:1) previous history of CV disease,2) biomarkers – troponin and NT-proBNP3)age,4) CV risk factors -HTN, DM,
Join our expert panel as they discuss the role of Janus kinase (JAK) inhibitors in the treatment of axial spondyloarthritis (axSpA). Credit available for this activity expires: 4/24/25 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/1000707?ecd=bdc_podcast_libsyn_mscpedu
Lewis C. Cantley, PhD, is a Professor of Cell Biology at Harvard Medical School. Prior to this appointment, he was the Margaret and Herman Sokol Professor and Meyer Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medical College/Ronald P. Stanton Clinical Cancer Program at New York Presbyterian Hospital (2012-22). Dr. Cantley is a graduate of West Virginia Wesleyan College, obtained a PhD in biophysical chemistry from Cornell University, completed postdoctoral training at Harvard University, and subsequently taught and conducted research in biochemistry, physiology and cancer biology at Beth Israel Deaconess Medical Center and Harvard Medical School. His laboratory discovered the PI 3-Kinase pathway that plays a critical role in insulin signaling and in cancers.Dr. Cantley was elected to the National Academy of Inventors in 2020, the Institute of Medicine in 2014, the National Academy of Sciences in 2001, and the American Academy of Arts and Sciences in 1999. Among his other awards are the ASBMB Avanti Award for Lipid Research in 1998, the Heinrich Wieland Preis for Lipid Research in 2000, the Caledonian Prize from the Royal Society of Edinburgh in 2002, the 2005 Pezcoller Foundation–AACR International Award for Cancer Research, the 2009 Rolf Luft Award for Diabetes and Endocrinology Research from the Karolinska Institute, Stockholm, the 2011 Pasrow Prize for Cancer Research, the 2013 Breakthrough in Life Sciences Prize and the 2013 Jacobaeus Prize for Diabetes Research from the Karolinska Institute and the 2015 AACR Princess Takamatsu Memorial Lectureship.
Do you know how to integrate the current evidence about Janus kinase (JAK) inhibitors? Credit available for this activity expires: 2/28/25 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/1000237?ecd=bdc_podcast_libsyn_mscpedu
References Biomedicines 2023, 11(7), 1804 BMC Biology. 2011. 9:85 Cancer Res. 2011 Jan 15;71(2):293-7. FEBS Lett.2019.593.17:2428-2451 Verdi, G. 1841. Nabucco Overture https://youtu.be/OseGETWEnCo?si=LhiIQV-N0-_Z_s-s Lennon&McCartney. 1966 "For No One". Beatles: Revolver. https://youtu.be/sep5E3ssXLQ?si=WLtMrP-Xq279qZXl --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support
This podcast covers the regulation of pyruvate kinase allosterically and by hormone-dependent (insulin & glucagon) covalent modification. --- Send in a voice message: https://podcasters.spotify.com/pod/show/a-j-ghalayini/message
References Nature 2019.volume 575, pages 361–365 Cells 2022, 11(21), 3339 Guerra: Polypeptide, endomembranous lipid homeostasis, and bioenergetics lecture archives. --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support
BUFFALO, NY- February 7, 2024 – A new #research perspective was #published in Oncotarget's Volume 15 on February 5, 2024, entitled, “Preclinical and clinical evaluation of the Janus Kinase inhibitor ruxolitinib in multiple myeloma.” In this new paper, researchers Ashley Del Dosso, Elizabeth Tadevosyan, and James R. Berenson from ONCOtherapeutics, Berenson Cancer Center, and Institute for Myeloma and Bone Cancer Research discussed multiple myeloma (MM) — the most common primary malignancy of the bone marrow. No established curative treatment is currently available for patients diagnosed with MM. In recent years, new and more effective drugs have become available for the treatment of this B-cell malignancy. These new drugs have often been evaluated together and in combination with older agents. However, even these novel combinations eventually become ineffective; and, thus, novel therapeutic approaches are necessary to help overcome resistance to these treatments. Recently, the Janus Kinase (JAK) family of tyrosine kinases, specifically JAK1 and JAK2, has been shown to have a role in the pathogenesis of MM. Preclinical studies have demonstrated a role for JAK signaling in direct and indirect growth of MM and downregulation of anti-tumor immune responses in these patients. Also, inhibition of JAK proteins enhances the anti-MM effects of other drugs used to treat MM. These findings have been confirmed in clinical studies which have further demonstrated the safety and efficacy of JAK inhibition as a means to overcome resistance to currently available anti-MM therapies. Additional studies will provide further support for this promising new therapeutic approach for treating patients with MM. “The following sections of this article will be focused on studies of RUX [Ruxolitinib] in the preclinical [21–24] and clinical settings [18–20] focused on the treatment of relapsed/refractory (RR) MM.” DOI - https://doi.org/10.18632/oncotarget.28547 Correspondence to - James R. Berenson - jberenson@berensoncancercenter.com Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28547 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, multiple myeloma, ruxolitinib, JAK/STAT, cytokine, clinical trial 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: Facebook - https://www.facebook.com/Oncotarget/ X - 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/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
References J Immunol. 2018 Feb 1; 200(3): 915–927 Cells. 2020 Jan; 9(1): 198. Cells. 2022 Apr; 11(7): 1105 Nature Comm. 2020. volume 11, Article number: 35 Schubert F. 1829. Fantasie in F minor. D940 https://youtu.be/UyjzqPPXDcw?si=XW_SMP7j-Kza8pmq Winwood, Capaldi and Wood. 1967 (Traffic). "Dear Mr Fantasy" https://youtu.be/dyMiUmrouZU?si=1ZSdXupm3WFBAxTz --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support
Once in a while there's a surfeit of positive news in the field of medicine. This week was one of 'em.
References Front Immunol. 2019; 10: 14 Cancer Immunol Immunother. 2016 Apr;65(4):441-52 Anal Cell Pathol (Amst).2018; 2018: 787.1814. Molecular Cancer 2020. volume 19, Article number: 39 Cohan, G. 1917. "Over There" https://youtu.be/BYV044H5muI?si=LdANMG6dtXeC14tj --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support
On this episode, Dr. Rachael Grace is in conversation with Claire Egan, Senior Genetic Counselor with InformedDNA, to talk all about genetics. SHOW DESCRIPTION Just Listen: Voices of PK Deficiency is a podcast about Pyruvate Kinase Deficiency and is intended for patients, caregivers, providers, and the greater community of people who are impacted by PKD. Each episode, Just Listen: Voices of PK Deficiency strives to provide listeners with critical education, the latest scientific updates, and voices from the PKD community. Learn more about PKD by visiting KnowPKDeficiency.com or connect with KnowPKDeficiency on Facebook: bit.ly/KnowPKD and Instagram shorturl.at/gmFT4. TRANSPARENCY STATEMENT Just Listen: Voices of PK Deficiency and KnowPKDeficiency.com are made possible by Agios Pharmaceuticals Inc. Visit Agios.com to learn more. The following Agios-supported programs are intended for informational and educational purposes only and are not intended as medical advice. Please speak with your healthcare professional before making any treatment decisions. Host Rachael Grace and guest Claire Egan have been compensated for their time.
Guest: Bruce H. Cohen, MD, FAAN Thymidine kinase 2 deficiency is a very rare disorder that presents several diagnostic and treatment challenges. Learn more about those challenges along with the clinical manifestations of thymidine kinase 2 deficiency and the importance of taking a multidisciplinary approach to care with Dr. Bruce H. Cohen, Chair of the NeuroDevelopmental Science Center at Akron Children's Hospital.
Dr. Rachael Grace returns with patient advocate (and PK Deficiency TikTok influencer) Karla Chichester. On this episode, Dr. Grace and Karla dispel some of the biggest myths surrounding Pyruvate Kinase Deficiency. Originally aired on September 29, 2022. SHOW DESCRIPTION Just Listen: Voices of PK Deficiency is a podcast about Pyruvate Kinase Deficiency (PK Deficiency) and is intended for patients, caregivers, providers, and the greater community of people who are impacted by PKD. Each episode, Just Listen: Voices of PK Deficiency strives to provide listeners with critical education, the latest scientific updates, and voices from the PKD community. Learn more about PKD by visiting KnowPKDeficiency.com or connect with KnowPKDeficiency on Facebook: bit.ly/KnowPKD and Instagram shorturl.at/gmFT4. TRANSPARENCY STATEMENT Just Listen: Voices of PK Deficiency and KnowPKDeficiency.com are made possible by Agios Pharmaceuticals Inc. Visit Agios.com to learn more. The following Agios-supported programs are intended for informational and educational purposes only and are not intended as medical advice. Please speak with your healthcare professional before making any treatment decisions. Guest Host, Dr. Rachel Grace and Karla Chichester been compensated for their time.
References Cell. 2020 Jul 23; 182(2):404–416.e14. Nature Communications 2020. volume 11,3146 Curr Genet. 2021 Feb; 67(1):19–26 --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support
Jenna Lesser is originally from NY, but she's been a Baltimore resident since she began her undergrad at Johns Hopkins in 2011. She earned her Bachelor's degree with a major in biology and a minor in bioethics. After working as a laboratory technician in neurogastroenterology for two years, she began graduate school at the University of Maryland Baltimore.She studied the impact of aging on osteocyte biology, mechanisms by which bones respond to mechanical load, and the contribution of a protein called Calcium/calmodulin-dependent Kinase 2 on the homeostasis of bone mass. She just completed her PhD! She hopes to take her expertise into a career in science policy. When she's not in the lab, teaches and practices yoga, staying connected to her roots as a dancer and gymnast, and plays field hockey. To learn more about Dr. Lesser, check out:Instagram: @jleser
On today's episode, we travel to New Orleans for a discussion about aging with pyruvate kinase deficiency (PKD) with returning guests Jill Welle and Tamara Schryver. Janie Davis, Associate Director Patient Advocacy at Agios Pharmaceuticals, leads the conversation. SHOW DESCRIPTION Just Listen: Voices of PK Deficiency is a podcast about Pyruvate Kinase Deficiency and is intended for patients, caregivers, providers, and the greater community of people who are impacted by PKD. Each episode, Just Listen: Voices of PK Deficiency strives to provide listeners with critical education, the latest scientific updates, and voices from the PKD community. Learn more about PKD by visiting KnowPKDeficiency.com or connect with KnowPKDeficiency on Facebook: bit.ly/KnowPKD and Instagram shorturl.at/gmFT4. TRANSPARENCY STATEMENT Just Listen: Voices of PK Deficiency and KnowPKDeficiency.com are made possible by Agios Pharmaceuticals Inc. Visit Agios.com to learn more. The following Agios-supported programs are intended for informational and educational purposes only and are not intended as medical advice. Please speak with your healthcare professional before making any treatment decisions. Host Rachel Grace and guest Matthew Heeney have been compensated for their time.
On this episode, we interview Alejandra Watson and Laura Miller D'Angelo of Pyruvate Kinase Deficiency Foundation. We learn more about the organization as well as Alejandra's experience as a caregiver for a child with PKD as well as Laura's experience living with PKD. SHOW DESCRIPTION Just Listen: Voices of PK Deficiency is a podcast about pyruvate kinase deficiency (PK Deficiency) and is intended for patients, caregivers, providers, and the greater community of people who are impacted by PKD. Each episode, Just Listen: Voices of PK Deficiency strives to provide listeners with critical education, the latest scientific updates, and voices from the PKD community. Learn more about PKD by visiting KnowPKDeficiency.com or connect with KnowPKDeficiency's on Facebook: bit.ly/KnowPKD. TRANSPARENCY STATEMENT Just Listen: Voices of PK Deficiency and KnowPKDeficiency.com are made possible by Agios Pharmaceuticals Inc. Visit Agios.com to learn more. The following Agios-supported programs are intended for informational and educational purposes only and are not intended as medical advice. Please speak with your healthcare professional before making any treatment decisions. Host featured in this episode have been compensated for their time.
In this episode, we review the high-yield topic of Pyruvate Kinase Deficiency from the Hematology section. Follow Medbullets on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbullets --- Send in a voice message: https://podcasters.spotify.com/pod/show/medbulletsstep1/message
References Immunity. 2021 Feb 9; 54(2): 308–323.e6. J Endocrinol. 2003 Sep;178(3):479-89. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message
Janus kinase inhibitor therapy and venous thromboembolism risk factors by AORNJournal
References Neural Plasticity. 2019; 2019: 1648736. Molecular Pharmacology May 2017, 91 (5) 451-463. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message
References Dr Guerra EtOH lectures Physiol Rev 2016. 96: 1261–1296. Clinical and Molecular Teratology. 2016. Volume 106, Issue 9 Pages 749–760 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message
Dr Eva Hoytema van Konijnenburg describes the case of a patient with mevalonate kinase deficiency presenting solely with neurological symptoms and without an inflammatory component. Isolated neurological presentations of mevalonate kinase deficiency Eva Hoytema van Konijnenburg, et al https://doi.org/10.1002/jmd2.12348
This episode: Bacteria can use blobs of disordered proteins to quickly adapt to new conditions! Thanks to Dr. Saumya Saurabh for his contribution! Download Episode (10.9 MB, 15.9 minutes) Show notes: Microbe of the episode: Drosophila melanogaster Micropia virus Takeaways Bacteria can adapt to environmental fluctuations via mechanisms operating at the various levels of the central dogma, or metabolism (stringent response). Recently, researchers at Stanford University discovered a mechanism that allows bacteria to sense and rapidly adapt to nutrient fluctuations by simply tuning protein self-assembly as a function of nutrient availability. Termed membraneless organelles or condensates, these proteinaceous assemblies can dynamically sequester key signaling enzymes within them in response to environmental cues. Biophysical adaptation mediated by organelles is fast, reversible, and facile; thereby representing a crucial step in the mechanistic understanding of microbial adaptation. Journal Paper: Saurabh S, Chong TN, Bayas C, Dahlberg PD, Cartwright HN, Moerner WE, Shapiro L. 2022. ATP-responsive biomolecular condensates tune bacterial kinase signaling. Sci Adv 8:eabm6570. Other interesting stories: Bacteria produce biofuel from carbon dioxide, light, and solar power-generated electricity Vine that can mimic leaves of different trees may get info from bacteria (paper) Email questions or comments to bacteriofiles at gmail dot com. Thanks for listening! Subscribe: Apple Podcasts, Google Podcasts, Android, or RSS. Support the show at Patreon, or check out the show at Twitter or Facebook.
References Dr Guerra's lipid lectures Front Pharmacol. 2020; 11: 569802 Biomolecules 2022, 12(10), 1434; https://doi.org/10.3390/biom12101434 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message
Dr. Dan Regan discusses his OutSmarting Osteosarcoma funded work on Focal Adhesion Kinase (FAK) inhibition to improve losartan-sunitinib immunotherapy in metastatic osteosarcoma. - Dr. Dan Regan is an Assistant Professor at the Flint Animal Cancer Center at Colorado State University and he is one of our OutSmarting Osteosarcoma 2022 grant recipients. Dr. Regan received his DVM degree from the University of Georgia and subsequently completed his residency training in veterinary anatomic pathology and PhD in the Department of Microbiology, Immunology, and Pathology (MIP) at Colorado State University. In 2018 he joined the Flint Animal Cancer Center and MIP in the College of Veterinary Medicine and Biomedical Sciences at Colorado State University. The focus of Dr. Regan's laboratory is to increase our understanding of the interplay between the immune system and (non-immune) tumor stroma, and how these compartments of the tumor microenvironment promote metastasis as well as respond to and mediate extrinsic mechanisms of resistance to anti-cancer therapy. To investigate this area of cancer biology, his laboratory utilizes a combination of in vitro 3-dimensional tumor co-culture models and animal models, focusing on breast and bone cancer (osteosarcoma). Dr. Regan also has a strong interest in comparative oncology and leveraging naturally occurring cancers in dogs as both a surrogate and intermediary model to evaluate and validate his laboratory's investigations into the tumor microenvironment. In collaboration with the laboratory of Dr. Steve Dow, his lab conducted immunotherapy clinical studies in dogs with spontaneous osteosarcoma and these study results have led to a phase I clinical trial in children with osteosarcoma. His lab's continued long-term research goal is to fully elucidate the mechanisms by which tumors prime non-malignant host stromal cells of distant organs to promote their metastasis and chemo-resistance, in order to identify novel targets for host-directed stromal therapies which “poison the soil” for effective combination with conventional tumor cell targeted drugs. --- What We Do at MIB Agents: PROGRAMS: ✨ End-of-Life MISSIONS ✨ Gamer Agents ✨ Agent Writers ✨ Prayer Agents ✨ Healing Hearts - Bereaved Parent Support ✨ Ambassador Agents - Peer Support ✨ Warrior Mail ✨ Young Adult Survivorship Support Group ✨ EDUCATION for physicians, researchers and families: ✨ OsteoBites, weekly webinar & podcast with thought leaders and innovators in Osteosarcoma ✨ MIB Book: Osteosarcoma: From our Families to Yours ✨ RESEARCH: Annual MIB FACTOR Research Conference ✨ Funding $100,000 annually for OS research ✨ MIB Testing & Research Directory ✨ The Osteosarcoma Project partner with Broad Institute of MIT and Harvard ... Kids are still dying with 40+ year old treatments. Help us MakeItBetter.
In this podcast, expert clinicians will review recent updates in the safety data regarding Janus kinase (JAK) inhibitors and discuss the appropriate selection of candidates for safe and effective use of JAK inhibitor therapy.
Dr. Rachael Grace and patient advocate (and PKD TikTok influencer) Karla Chichester are back to bust more myths about PKD! This is part two of our MythBusters: PKD Edition series. SHOW DESCRIPTION Just Listen: Voices of PK Deficiency is a podcast about Pyruvate Kinase Deficiency (PK Deficiency) and is intended for patients, caregivers, providers, and the greater community of people who are impacted by PKD. Each episode, Just Listen: Voices of PK Deficiency strives to provide listeners with critical education, the latest scientific updates, and voices from the PKD community. Learn more about PKD by visiting KnowPKDeficiency.com or connect with KnowPKDeficiency on Facebook: bit.ly/KnowPKD and Instagram shorturl.at/gmFT4. TRANSPARENCY STATEMENT Just Listen: Voices of PK Deficiency and KnowPKDeficiency.com are made possible by Agios Pharmaceuticals Inc. Visit Agios.com to learn more. The following Agios-supported programs are intended for informational and educational purposes only and are not intended as medical advice. Please speak with your healthcare professional before making any treatment decisions. Guest Host, Dr. Rachel Grace and Karla Chichester have been compensated for their time.
Dr. Rachael Grace returns with patient advocate (and PK Deficiency TikTok influencer) Karla Chichester. On this episode, Dr. Grace and Karla dispel some of the biggest myths surrounding Pyruvate Kinase Deficiency. SHOW DESCRIPTION Just Listen: Voices of PK Deficiency is a podcast about Pyruvate Kinase Deficiency (PK Deficiency) and is intended for patients, caregivers, providers, and the greater community of people who are impacted by PKD. Each episode, Just Listen: Voices of PK Deficiency strives to provide listeners with critical education, the latest scientific updates, and voices from the PKD community. Learn more about PKD by visiting KnowPKDeficiency.com or connect with KnowPKDeficiency on Facebook: bit.ly/KnowPKD and Instagram shorturl.at/gmFT4. TRANSPARENCY STATEMENT Just Listen: Voices of PK Deficiency and KnowPKDeficiency.com are made possible by Agios Pharmaceuticals Inc. Visit Agios.com to learn more. The following Agios-supported programs are intended for informational and educational purposes only and are not intended as medical advice. Please speak with your healthcare professional before making any treatment decisions. Guest Host, Dr. Rachel Grace and Karla Chichester been compensated for their time.
Kinase inhibitors have become staples in the arsenal to battle cancer. These medicines can disrupt the cell signaling that drives the growth and spread of tumors. There are more than 30 approved kinase inhibitors today, but they often have dose limiting toxicities, in part because they often lack specificity and can have activity against multiple kinases at once. Blueprint Medicines is seeking to develop next-generation kinase inhibitors that are highly selective to treat genomically-defined cancers and rare diseases. We spoke to Fouad Namouni, president of research and development for Blueprint, about the company's discovery platform, the large unexplored territory of kinases, and what makes Blueprint's kinase medicines next-generation.
A new research paper was published in Oncotarget on August 4, 2022, entitled, “Kinase activity profiling in renal cell carcinoma, benign renal tissue and in response to four different tyrosine kinase inhibitors.” Kinase activity is frequently altered in renal cell carcinoma (RCC), and tyrosine kinase inhibitors (TKIs) are part of the standard treatment strategy in patients with metastatic disease. However, there are still no established biomarkers to predict clinical benefits of a specific TKI. “Despite a number of new treatment options improving RCC patients' disease control rates and survival, the lack of useful biomarkers remains a major clinical concern.” In the current study, researchers Andliena Tahiri, Katarina Puco, Faris Naji, Vessela N. Kristensen, Glenny Cecilie Alfsen, Lorant Farkas, Frode S. Nilsen, Stig Müller, Jan Oldenburg, and Jürgen Geisler, from University of Oslo, Oslo University Hospital, Akershus University Hospital, and Pamgene International BV, performed protein tyrosine kinase (PTK) profiling using PamChip® technology. “The aim of this study was to identify differences in PTK activity between normal and malignant kidney tissue obtained from the same patient, and to investigate the inhibitory effects of TKIs frequently used in the clinics: sunitinib, pazopanib, cabozantinib and tivozanib.” The results showed that 36 kinase substrates differ (FDR < 0.05) between normal and cancer kidney tissue, where members of the Src family kinases and the phosphoinositide-3-kinase (PI3K) pathway exhibit high activity in renal cancer. Furthermore, ex vivo treatment of clear cell RCC with TKIs revealed that pathways such as Rap1, Ras and PI3K pathways were strongly inhibited, whereas the neurotrophin pathway had increased activity upon TKI addition. Their assay showed that tivozanib and cabozantinib exhibited greater inhibitory effects on PTK activity compared to sunitinib and pazopanib, implying they might be better suitable as TKIs for selected RCC patients. “The results of our study contribute to better understanding of the changes in kinase activity in RCC tumor cells involved in fundamental oncogenic cellular processes and the ex vivo effect of TKIs. We found tivozanib and cabozantinib to be more potent TKIs in RCC samples than sunitinib or pazopanib. The next step will be to correlate the efficacy and toxicity in individual patients with their respective kinase activity of normal and malignant kidney tissue.” DOI: https://doi.org/10.18632/oncotarget.28257 Correspondence to: Jürgen Geisler – Email: juergen.geisler@medisin.uio.no Keywords: kidney cancer, kinase activity, tyrosine kinase inhibitors, renal cell carcinoma, tyrosine kinase 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: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
Susan S. Taylor, a distinguished professor at the University of California, San Diego, won the 2022 Herbert Tabor Research Award, which is given for excellence in biological chemistry and molecular biology and contributions to the community of scientists. Taylor has done pioneering structural studies of protein kinase A, revealing fundamental themes for all protein kinases. She presented her award lecture, "My journey with cAMP-dependent protein kinase," on Sunday, April 3, at the 2022 ASBMB Annual Meeting, held in conjunction with Experimental Biology, in Philadelphia. Learn more about her work: https://www.asbmb.org/asbmb-today/people/122321/taylor-s-career-began-as-a-med-school-detour.
Alex Toker, winner of the 2022 Avanti Award in Lipids, which recognizes outstanding lipid research contributions, presented his lecture, "PI 3-Kinase signaling: A journey in three AKTs," on Monday, April 4, at the 2022 ASBMB Annual Meeting, held in conjunction with Experimental Biology, in Philadelphia. Learn more about his work: https://www.asbmb.org/asbmb-today/people/120721/toker-recognized-for-seminal-contributions-to-lip.
Go online to PeerView.com/XJG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Systemic lupus erythematosus (SLE) is an autoimmune disease associated with substantial morbidity and mortality, especially in women. The disease causes progressive damage to multiple organ systems and reduces quality of life. Improving your understanding of SLE heterogeneity at the clinical and mechanistic level can drive significant improvements across the care spectrum. In this expert-driven activity, you will hear the latest clinical evidence presented during the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress in Copenhagen, Denmark, with regard to the current treatment options for SLE and the potential for TYK2 inhibitors to change SLE management. Upon completion of this activity, participants should be better able to: Recognize the burden of SLE and the impact of delayed or suboptimal treatment on patient outcomes; Describe the mechanistic rationale and recent safety and efficacy data supporting a role for targeting TYK2 and BTK as potential therapeutic approaches in SLE; and Identify SLE patients who might benefit from emerging TYK2 and BTK inhibition strategies through clinical trial enrollment and recognizing potential implications for a future treatment paradigm.
Go online to PeerView.com/XJG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Systemic lupus erythematosus (SLE) is an autoimmune disease associated with substantial morbidity and mortality, especially in women. The disease causes progressive damage to multiple organ systems and reduces quality of life. Improving your understanding of SLE heterogeneity at the clinical and mechanistic level can drive significant improvements across the care spectrum. In this expert-driven activity, you will hear the latest clinical evidence presented during the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress in Copenhagen, Denmark, with regard to the current treatment options for SLE and the potential for TYK2 inhibitors to change SLE management. Upon completion of this activity, participants should be better able to: Recognize the burden of SLE and the impact of delayed or suboptimal treatment on patient outcomes; Describe the mechanistic rationale and recent safety and efficacy data supporting a role for targeting TYK2 and BTK as potential therapeutic approaches in SLE; and Identify SLE patients who might benefit from emerging TYK2 and BTK inhibition strategies through clinical trial enrollment and recognizing potential implications for a future treatment paradigm.
PeerView Family Medicine & General Practice CME/CNE/CPE Video Podcast
Go online to PeerView.com/XJG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Systemic lupus erythematosus (SLE) is an autoimmune disease associated with substantial morbidity and mortality, especially in women. The disease causes progressive damage to multiple organ systems and reduces quality of life. Improving your understanding of SLE heterogeneity at the clinical and mechanistic level can drive significant improvements across the care spectrum. In this expert-driven activity, you will hear the latest clinical evidence presented during the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress in Copenhagen, Denmark, with regard to the current treatment options for SLE and the potential for TYK2 inhibitors to change SLE management. Upon completion of this activity, participants should be better able to: Recognize the burden of SLE and the impact of delayed or suboptimal treatment on patient outcomes; Describe the mechanistic rationale and recent safety and efficacy data supporting a role for targeting TYK2 and BTK as potential therapeutic approaches in SLE; and Identify SLE patients who might benefit from emerging TYK2 and BTK inhibition strategies through clinical trial enrollment and recognizing potential implications for a future treatment paradigm.
PeerView Family Medicine & General Practice CME/CNE/CPE Audio Podcast
Go online to PeerView.com/XJG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Systemic lupus erythematosus (SLE) is an autoimmune disease associated with substantial morbidity and mortality, especially in women. The disease causes progressive damage to multiple organ systems and reduces quality of life. Improving your understanding of SLE heterogeneity at the clinical and mechanistic level can drive significant improvements across the care spectrum. In this expert-driven activity, you will hear the latest clinical evidence presented during the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress in Copenhagen, Denmark, with regard to the current treatment options for SLE and the potential for TYK2 inhibitors to change SLE management. Upon completion of this activity, participants should be better able to: Recognize the burden of SLE and the impact of delayed or suboptimal treatment on patient outcomes; Describe the mechanistic rationale and recent safety and efficacy data supporting a role for targeting TYK2 and BTK as potential therapeutic approaches in SLE; and Identify SLE patients who might benefit from emerging TYK2 and BTK inhibition strategies through clinical trial enrollment and recognizing potential implications for a future treatment paradigm.
Go online to PeerView.com/XJG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Systemic lupus erythematosus (SLE) is an autoimmune disease associated with substantial morbidity and mortality, especially in women. The disease causes progressive damage to multiple organ systems and reduces quality of life. Improving your understanding of SLE heterogeneity at the clinical and mechanistic level can drive significant improvements across the care spectrum. In this expert-driven activity, you will hear the latest clinical evidence presented during the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress in Copenhagen, Denmark, with regard to the current treatment options for SLE and the potential for TYK2 inhibitors to change SLE management. Upon completion of this activity, participants should be better able to: Recognize the burden of SLE and the impact of delayed or suboptimal treatment on patient outcomes; Describe the mechanistic rationale and recent safety and efficacy data supporting a role for targeting TYK2 and BTK as potential therapeutic approaches in SLE; and Identify SLE patients who might benefit from emerging TYK2 and BTK inhibition strategies through clinical trial enrollment and recognizing potential implications for a future treatment paradigm.
Visit https://thermofisher.com/bctl to register for your free Bringing Chemistry to Life T-shirt and https://www.thermofisher.com/chemistry-podcast/ to access the extended video version of this episode and the episode summary sheet, which contains links to recent publications and additional content recommendations for our guest. You can access the extended video version of this episode via our YouTube channel to hear, and see, more of the conversation!Chemical biology is a relatively recent discipline where thinking about biomolecules as big organic molecules isn't shocking, but it was completely revolutionary just 3 or 4 decades ago. What is undeniable is that chemistry offers a new lens to observe, interact with and alter biological phenomena. Chemistry opens the possibility to understand biomolecules at the atomic level and to leverage traditional organic chemistry methods to change their function, ultimately influencing macroscopic biological phenomena.Dr. Shanique Borteley Alabi has been thinking about how chemicals can influence humans ever since childhood observations of her grandfather at work in his pharmacy, in Ghana. She now uses chemistry to influence the interaction between cellular proteins by designing small molecules that work as “glues” for macromolecules. She spent her PhD developing “proteolysis targeted chimeras” (ProTaC), the use of small molecules with affinity for both a specific protein target and for kinases that tag proteins to initiate their degradation. She now works on similar concepts to selectively initiate and promote the interaction between natural proteins with the objective of amplifying specific natural pathways to treat disease. This is the frontier of drug development, going beyond simple competitive inhibition and promising a way to develop drugs for undruggable targets.
The emergence of tyrosine kinase inhibitors represented a major advance in the fight against cancer, but the ability of tumors to mutate and develop resistance to these therapies remains a challenge. Theseus Pharmaceuticals is developing what it calls “pan-variant” kinase inhibitors in the hopes of outsmarting tumors by anticipating the range of kinases that may drive their spread and growth as they change. We spoke to Tim Clackson, president and CEO of Theseus Pharmaceuticals, about its structural-based approach to drug development, how it determines the appropriate targets for its pan-variant kinase inhibitors, and why it believes its next-generation TKIs can overcome the challenge of drug resistance.
Treatment approved for hospitalized COVID-19 patients; Update on Varenicline supply; Limits have been set for the Janssen COVID-19 vaccine; Safety alert issued for a COVID-19 test; And certain hemodialysis machines may carry the potential for chemical exposure.
In which Neil Vasan, assistant professor of medicine and medical oncologist at the Columbia University Irving Medical Center, and Vaibhav discuss the biochemistry and structural biology of kinases, as well as their salience in cancer development and progression. Neil tells the story behind his critical discovery of hyper-activating double mutations cooccurring in cis on PI3K alleles, discusses his group's use of deep mutational scanning in elucidating mechanisms of drug resistance and disease pathogenesis, and describes his efforts to illuminate the dark phosphoproteome. As well, he discusses how proteomics complements genomic approaches to understanding cancer and provides advice for aspiring physician-scientists.
On this episode, we discuss the Pyruvate Kinase Deficiency Advocacy Advisory Council, (AAC), an international, multi-disciplinary group of experts including patients, caregivers, patient advocates and clinicians. The AAC launched a survey, which received 275 respondents from 11 countries, making it the largest of its kind for this community which resulted in a White Paper. The White Paper shares the results of the international survey exploring communication between PK deficiency patients and caregivers and their hematologists. Agios funds and supports the AAC. We speak with AAC member, Dr. Rachael Grace, a pediatric hematologist and a clinical researcher at the Boston Children's Cancer and Blood Disorders Center about the AAC and the White Paper. We also hear from former guests Tamara Schryver and Carl Lander of Thrive with PK Deficiency Patient Organization (thrivewithpkd.org) as well as Alejandra Watson and Laura Miller-D'Angelo of the Pyruvate Kinase Deficiency Foundation (pkdf.org) who are also AAC members. To read the AAC White Paper, Pyruvate Kinase Deficiency: Reflections on the Patient Experience to Support Treatment and Care white paper go to: https://thalassaemia.org.cy/pk-deficiency/. SHOW DESCRIPTION Just Listen: Voices of PK Deficiency is a podcast about pyruvate kinase deficiency (PK Deficiency) and is intended for patients, caregivers, providers, and the greater community of people who are impacted by PKD. Each episode, Just Listen: Voices of PK Deficiency strives to provide listeners with critical education, the latest scientific updates, and voices from the PKD community. Learn more about PKD by visiting KnowPKDeficiency.com or connect with KnowPKDeficiency's on Facebook: bit.ly/KnowPKD. TRANSPARENCY STATEMENT Just Listen: Voices of PK Deficiency and KnowPKDeficiency.com are made possible by Agios Pharmaceuticals Inc. Visit Agios.com to learn more. The following Agios-supported programs are intended for informational and educational purposes only and are not intended as medical advice. Please speak with your healthcare professional before making any treatment decisions. Host and guests featured in this episode have been compensated for their time. Produced by BloodStream Media
"Defining the Diagnosis and Management of Pyruvate Kinase Deficiency"
References Dr. Guerra lecture notes Circulation Research Volume 128, Issue 10, 14 May 2021; Pages 1419-1420 Adv Exp Med Biol . 2017;960:135-160. Current Opinion in Clinical Nutrition and Metabolic Care Issue: Volume 21(4), July 2018, p 260-266 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support
On this episode, we interview Alejandra Watson and Laura Miller D'Angelo of Pyruvate Kinase Deficiency Foundation. We learn more about the organization as well as Alejandra's experience as a caregiver for a child with PKD as well as Laura's experience living with PKD. SHOW DESCRIPTION Just Listen: Voices of PK Deficiency is a podcast about pyruvate kinase deficiency (PK Deficiency) and is intended for patients, caregivers, providers, and the greater community of people who are impacted by PKD. Each episode, Just Listen: Voices of PK Deficiency strives to provide listeners with critical education, the latest scientific updates, and voices from the PKD community. Learn more about PKD by visiting KnowPKDeficiency.com or connect with KnowPKDeficiency's on Facebook: bit.ly/KnowPKD. TRANSPARENCY STATEMENT Just Listen: Voices of PK Deficiency and KnowPKDeficiency.com are made possible by Agios Pharmaceuticals Inc. Visit Agios.com to learn more. The following Agios-supported programs are intended for informational and educational purposes only and are not intended as medical advice. Please speak with your healthcare professional before making any treatment decisions. Host featured in this episode have been compensated for their time.
Don Cleveland, PhD, shares new research on the role of chromothripsis, targeting cancers driven by ecDNA and more. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37586]
On this episode, we interview Tamara Schryver and Carl Lander of Thrive with Pyruvate Kinase Deficiency Patient Organization. We learn more about Thrive as well as Tamara and Carl's experiences living with PKD. SHOW DESCRIPTION Just Listen: Voices of PK Deficiency is a podcast about pyruvate kinase deficiency (PK Deficiency) and is intended for patients, caregivers, providers, and the greater community of people who are impacted by PKD. Each episode, Just Listen: Voices of PK Deficiency strives to provide listeners with critical education, the latest scientific updates, and voices from the PKD community. Learn more about PKD by visiting KnowPKDeficiency.com or connect with KnowPKDeficiency's on Facebook: bit.ly/KnowPKD. TRANSPARENCY STATEMENT Just Listen: Voices of PK Deficiency and KnowPKDeficiency.com are made possible by Agios Pharmaceuticals Inc. Visit Agios.com to learn more. The following Agios-supported programs are intended for informational and educational purposes only and are not intended as medical advice. Please speak with your healthcare professional before making any treatment decisions. Host and guests featured in this episode have been compensated for their time. Produced by BloodStream Media