Podcasts about treg

Treg and Bobby go into the Biblical reasons to have pastoral interns. Bobby talks about how to have an intern for minimal money, what to do with an intern, and how to mentor while still being an assistant pastor.    Treg's Book: https://www.amazon.com/Ministering-Middle-Becoming-Assistant-Pastor/dp/1632967464  Treg's Website: https://tregspicer.com/  Treg's Blog: https://tregspicer.com/blog/  Bobby's Contact: info@trinitybc.church Bobby's Books: http://bit.ly/4e3ysEt  Bobby's Articles: https://www.thegospelcoalition.org/profile/bobby-jamieson/   

This week, the party wraps up their dealings with Treg and the ever-demanding Lady Shimmersnips. Fresh off a narrow brush with death, some of the group decide to press their luck even further—diving into the shadier, underground offerings of Highhelm. What could possibly go wrong?

Chris Parrish has been the senior pastor at Buck Run Baptist Church for one hear. He talks to Treg about how Pastor York set up him to succeed.

This week, as the party puts the final nail in the House of Six Nails, Ektar asks them to lend a hand to his friend Treg in the Depths—who's having trouble with his prized crab. Let's just hope no one has a shellfish allergy!

In Episode 42, Wes interviews Pastor Treg Spicer of Faith Baptist Church in Morgantown WV. Topics covered include:Treg's journey to faith in ChristThe value of physical fitnessThe importance of pursuing both biblical proficiency and vocational excellenceHow God used near death experiences in Treg's life What it was like surviving a heart attack

Send us a textIf you like learning about the mysteries of the immune system - you're going to like this episode! Dr Yas makes learning about the immune system fun - even going so far as to create poke-immune cards on instagram. If you are a pokemon fan & science lover - you'll love it. Check out an example below.Dr Yasmin Mohseni, PhD is an immunologist with 6+ years of experience in the cell and gene therapy biotech space, specialising in immunotherapy for cancer and immunoregulation. Dr Mohseni earned her PhD in Immunotherapy from King's College London, where she focused on using engineered regulatory T cells (Tregs) to promote immune tolerance in solid organ transplantation with applications to autoimmunity. She began her industry journey at Quell Therapeutics, advancing Treg-based therapies, and now works at A2 Biotherapeutics in the cancer immunotherapy space, developing therapies for solid tumours. She currently serves as the scientific lead within Quality, bridging analytical strategy, process and product knowledge improvements within CMC.Dr. Yasmin Mohseni is an immunologist with an interest in immunology and cancer biotech. She discusses the emotional complexities of being an IBD patient while also being a scientist, the intricacies of the immune system, and her current role in developing immunotherapies for cancer treatment. The conversation highlights the importance of understanding the immune system's balance and the potential of immunotherapy in revolutionizing the future healthcare. In this conversation, Dr. Yasmin Mohseni delves into the complexities of the immune system, particularly in relation to Inflammatory Bowel Disease (IBD), immune memory and the effects of stress. The discussion highlights the mechanisms of immune responses, the role of cytokines, and how various factors, including hormones and stress, can influence immune health and disease progression.Takeaways-Dr. Yasmin Mohseni shares her experience of becoming an immunologist.Immunology is about communication between cells.T cells play a crucial role in fighting cancer.Immunotherapy is changing the landscape of cancer treatment.The immune system not only protects the body from invaders but also aids in healing and repair.Inflammation is a natural response to infection.Understanding the immune system can empower patients. IBD involves complex immune responses and genetic predispositions.Cytokines serve as crucial communicators in the immune system.Antibody presence does not always indicate immune memory.Chronic stress can lead to dysregulated immune responses.Pregnancy can alter immune responses, affecting autoimmune diseases..Understanding immune memory is essential for vaccine responses.The relationship between hormones and immunity is nuanced and complex.Follow us on instagram @crohns_and_colitis_dietitiansFollow us on youtube @thecrohnscolitisdietitiansWe love helping provide quality content on IBD nutrition and making it more accessible to all through our podcast, instagram and youtube channel. Creating the resources we provide comes at a significant cost to us. We dream of a day where we can provide even more free education, guidance and support to those with IBD like us. We need your support to do this. You can help us by liking episodes, sharing them on your social media, subscribing to you tube and telling others about us (your doctors, friends, family, forums/reddit etc). Can you do this for us? In return, I promise to continually level up what we do here.

Join us as we celebrate a major milestone — the 200th episode of the Xtalks Life Science Podcast! From groundbreaking biotech innovations to exclusive interviews with life science industry innovators and leaders, we've covered it all. Thank you for tuning in each week! We look forward to continuing to bring the latest and greatest across the pharma, biotech and medical industries! In this episode, Ayesha spoke with Arun Swaminathan, PhD, CEO of Coya Therapeutics, a company developing regulatory T cell (Treg) therapies targeting neurodegenerative, autoimmune and metabolic diseases. The company is developing a pipeline of therapies designed to enhance the function of dysregulated Tregs in various diseases, including ALS and Alzheimer's disease. Dr. Swaminathan has over 20 years of healthcare business executive experience. He began his career in clinical development, taking on commercial roles of increasing responsibility at Bristol Myers Squibb and Covance. Prior to joining Coya, Dr. Swaminathan served as chief business officer (CBO) at Actinium Pharmaceuticals and Alteogen, leading multi-billion-dollar deals. He also co-founded Lynkogen, a pre-clinical stage biotech, and served as its CEO. Dr. Swaminathan has a PhD in pharmaceutical sciences from the University of Pittsburgh.   Tune into the episode to hear more about Coya Therapeutics' innovative immunotherapeutic approach from Dr. Swaminathan.   For more life science and medical device content, visit the Xtalks Vitals homepage. https://xtalks.com/vitals/ Follow Us on Social Media Twitter: https://twitter.com/Xtalks Instagram: https://www.instagram.com/xtalks/ Facebook: https://www.facebook.com/Xtalks.Webinars/ LinkedIn: https://www.linkedin.com/company/xtalks-webconferences YouTube: https://www.youtube.com/c/XtalksWebinars/featured

We love to hear from our listeners. Send us a message.In this episode, Host Erin Harris sits down with Dr. Simrit Parmar, Founder of Cellenkos, to explore how the company is pioneering umbilical cord blood-derived Regulatory T cell (Treg) cell therapies for autoimmune and inflammatory diseases. Dr. Parmar shares the vision behind Cellenkos, the advantages of cord blood-derived Tregs over other sources, and how their CRANE technology platform enhances precision in targeting diseases. They also discuss key findings from their Phase 1b trial for CK0804, the challenges of scaling up off-the-shelf Treg therapies, and what's next for Cellenkos in 2025.Subscribe to the podcast!Apple | Spotify | YouTube

Treg and Vicky catch up on their weeks and how marathon training is going. Then they discuss how and when to introduce speed workouts into a training plan.

Treg and Vicky welcome the (in)famous Coach Nick on the podcast today where they discuss Nick's running journey, how he struggled with burnout, and how he ended up re-finding his love for running.

Dr. Simrit Parmar, Founder of Cellenkos, is developing T regulatory cell therapies from cord blood to treat aplastic anemia, myelofibrosis, and acute lymphoblastic leukemia. Their three-prong strategy focuses on resolving inflammation and alleviating the burden of transfusions. Treg cells from cord blood are naturally tolerant and do not risk rejection, meaning they can be administered to patients without the need for matching. The cells can be consistently manufactured in a scalable way and distributed globally. Simrit explains, "Tregs, the T regulatory cells, are actually regulators of our immune system. So if you think about it every day as a human being, we face many challenges. We face many insults and injuries to our body, both externally and internally, but our body has a way to maintain that balance. The T regulatory cells are the cells that are the mastermind of making sure that any response by our body, for example, to get rid of an antigen or to get rid of an irritant does not overstay the welcome because our body utilizes the mechanism of inflammation to get rid of these injuries or these insults."  "So umbilical cord blood is, or the umbilical cord is, the connection between the baby, the fetus, and the mother. And if you think about it, the baby is 50% mismatched to the mother, and nature allows it. Nature allows a permissive environment where the baby can grow and eventually give birth, and the whole species is advanced. What happens is that nature has allowed the tolerance, and one of the mechanisms by which this tolerance, the maternal-fetal tolerance, is induced by the very T regulatory cells that populate the conduit between the mother and the baby, is the cord blood. So what we did is harness the power that nature has bestowed upon these cells to just do one job and one job only, which is to resolve inflammation. This is the fundamental reason we went after cord blood as a starting material because as a physician and drug developer, we wanted to make sure that the product, the cells we're giving into the patient, are doing its job." #Biotechnology #DrugDevelopment #LifeSciences #AplasticAnemia #Myelofibrosis #GVHD #ALS #Tregs #CellTherapies #TargetedTherapies #AutoimmuneDiseases cellenkosinc.com   Listen to the podcast here  

Dr. Simrit Parmar, Founder of Cellenkos, is developing T regulatory cell therapies from cord blood to treat aplastic anemia, myelofibrosis, and acute lymphoblastic leukemia. Their three-prong strategy focuses on resolving inflammation and alleviating the burden of transfusions. Treg cells from cord blood are naturally tolerant and do not risk rejection, meaning they can be administered to patients without the need for matching. The cells can be consistently manufactured in a scalable way and distributed globally. Simrit explains, "Tregs, the T regulatory cells, are actually regulators of our immune system. So if you think about it every day as a human being, we face many challenges. We face many insults and injuries to our body, both externally and internally, but our body has a way to maintain that balance. The T regulatory cells are the cells that are the mastermind of making sure that any response by our body, for example, to get rid of an antigen or to get rid of an irritant does not overstay the welcome because our body utilizes the mechanism of inflammation to get rid of these injuries or these insults." "So umbilical cord blood is, or the umbilical cord is, the connection between the baby, the fetus, and the mother. And if you think about it, the baby is 50% mismatched to the mother, and nature allows it. Nature allows a permissive environment where the baby can grow and eventually give birth, and the whole species is advanced. What happens is that nature has allowed the tolerance, and one of the mechanisms by which this tolerance, the maternal-fetal tolerance, is induced by the very T regulatory cells that populate the conduit between the mother and the baby, is the cord blood. So what we did is harness the power that nature has bestowed upon these cells to just do one job and one job only, which is to resolve inflammation. This is the fundamental reason we went after cord blood as a starting material because as a physician and drug developer, we wanted to make sure that the product, the cells we're giving into the patient, are doing its job."  #Biotechnology #DrugDevelopment #LifeSciences #AplasticAnemia #Myelofibrosis #GVHD #ALS #Tregs #CellTherapies #TargetedTherapies #AutoimmuneDiseases   cellenkosinc.com   Download the transcript here  

Treg and Vicky recap their most recent races and give a little update on how training for their respective marathons are going. They discuss Treg's infamous race curse, Vicky's therapy updates, and hot takes (kinda...)

In this episode, we dive into the interplay between the gut microbiota (their postbiotics) and the immune system. We will examine how gut microbiome-derived metabolites, such as short-chain fatty acids (SCFAs) and polyphenol metabolites, influence immune function by modulating key cellular and molecular pathways within the intestinal mucosa. Additionally, we discuss strategies for supporting butyrate production and optimizing microbiome health to foster a balanced and resilient gut-immune axis. Topics: 1. Introduction Overview of the gut-immune axis. Importance of gut microbiome-derived metabolites in supporting immune function. 2. The Intestinal Barrier Layers of the intestinal wall Focus on mucosa, specifically the epithelium and lamina propria. 3. Structure of the Intestinal Layers The intestinal lumen, mucus layer, epithelium (with tight junctions), and lamina propria. Importance of the lamina propria as a hub for immune responses and structural integrity. 4. Cellular and Structural Components of the Lamina Propria Extracellular matrix (ECM): structural support. Fibroblasts and myofibroblasts. Lymphatic vessels: immune cell transport, linking mucosal and systemic immune systems. 5. Immune Cells in the Lamina Propria T cells: immune tolerance, regulatory T cells (Tregs). B cells: Secretory immunoglobulin A (sIgA). Dendritic cells: antigen sampling and presentation. Macrophages: pathogen clearance. Mast cells 6. Role of Secretory Immunoglobulin A (sIgA) Functions as a first-line defense in the intestinal mucus layer. Neutralizes pathogens, prevents epithelial adhesion. 7. Postbiotics Overview Bioactive compounds produced by gut microbiota. Examples: short-chain fatty acids (SCFAs) 8. Short-Chain Fatty Acids (SCFAs) and Their Functions Influence on Treg cells in the lamina propria, promoting immune tolerance. Butyrate also as an energy source for epithelial cells. 9. Supporting Butyrate Production Microbiome optimization to enhance beneficial butyrate-producing microbes. Use of prebiotics: resistant starch, soluble fibers, and polyphenols. Supplementation with sodium butyrate as an additional tool. 10. Other Postbiotics Antimicrobial peptides produced by beneficial microbes. Complex carbohydrates produced by beneficial microbes and can act as prebiotics. Polyphenol metabolites: Gut microbiota biotransforms polyphenols into bioactive metabolites with increased bioavailability. 11. Specific Polyphenols Examples: resveratrol, quercetin, and ellagitannins. Effects on intestinal barrier function, inflammation, and immune cell populations. "⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠75 Gut-Healing Strategies & Biohacks⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠" Follow Chloe on Instagram ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Follow Chloe on TikTok @chloe_c_porter Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠synthesisofwellness.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support

Treg and Vicky read out your 2024 running wins (thank your for the submissions!) and are extremely inspired by everything you've overcome this past year. It's been an awesome season 2 of the pod, see you in the new year!

Professor Piotr Trzonkowski, CEO of PolTREG, is focused on developing cell therapies for autoimmune diseases like type-1 diabetes and multiple sclerosis using polyclonal T-regulatory cell therapy. Treg cells are key in regulating the immune system and preventing autoimmune diseases. Clinical trials are showing promise for safe and effective treatments for preventing type-1 diabetes in pre-symptomatic patients and maintaining insulin production for years after treatment in those with this form of diabetes.   Piotr explains, "My initial research subject was vaccination in the elderly, and I was looking for the reasons they did not respond to the vaccine. It was initially on the flu vaccine. The same is valuable, for example, for the COVID-19 vaccine. What we found is that elderly people do not respond to the vaccines because of the high level of accumulation of T-regulatory cells. T-regulatory cells can suppress immune responses, which is bad for the elderly." "A very simple answer would be if you compare the immune system to kind of an army. The majority of the army fights with enemies. In the case of the immune system, these enemies are bacteria and viruses that attack us, and in each and every army, there must be police who keep an eye on the soldiers. So, the soldiers really fight with the enemies and do not fight with the self-tissue." "The T-regulatory cells are a kind of military police of the immune system, which really keeps an eye on the immune system. So, the immune system fights with bacteria and virus cells and does not touch our own tissues. We call it in immunology, keeping the immune tolerance. So, proper immune tolerance is very dependent on T-regulatory cells. We say that this is an immune-dominant mechanism. T-regulatory cells are present in each and every process where the immune system responds to the bacteria. So, we successfully fight the infection, and at the same time, we do not destroy ourselves." #PolTREG #TregCells TRegulatoryCells #CellTherapy #AutoimmuneDiseases #Diabetes #Type1Diabetes poltreg.com Download the transcript here

Professor Piotr Trzonkowski, CEO of PolTREG, is focused on developing cell therapies for autoimmune diseases like type-1 diabetes and multiple sclerosis using polyclonal T-regulatory cell therapy. Treg cells are key in regulating the immune system and preventing autoimmune diseases. Clinical trials are showing promise for safe and effective treatments for preventing type-1 diabetes in pre-symptomatic patients and maintaining insulin production for years after treatment in those with this form of diabetes.   Piotr explains, "My initial research subject was vaccination in the elderly, and I was looking for the reasons they did not respond to the vaccine. It was initially on the flu vaccine. The same is valuable, for example, for the COVID-19 vaccine. What we found is that elderly people do not respond to the vaccines because of the high level of accumulation of T-regulatory cells. T-regulatory cells can suppress immune responses, which is bad for the elderly." "A very simple answer would be if you compare the immune system to kind of an army. The majority of the army fights with enemies. In the case of the immune system, these enemies are bacteria and viruses that attack us, and in each and every army, there must be police who keep an eye on the soldiers. So, the soldiers really fight with the enemies and do not fight with the self-tissue." "The T-regulatory cells are a kind of military police of the immune system, which really keeps an eye on the immune system. So, the immune system fights with bacteria and virus cells and does not touch our own tissues. We call it in immunology, keeping the immune tolerance. So, proper immune tolerance is very dependent on T-regulatory cells. We say that this is an immune-dominant mechanism. T-regulatory cells are present in each and every process where the immune system responds to the bacteria. So, we successfully fight the infection, and at the same time, we do not destroy ourselves." #PolTREG #TregCells TRegulatoryCells #CellTherapy #AutoimmuneDiseases #Diabetes #Type1Diabetes poltreg.com Listen to the podcast here

In this episode, we examine the bidirectional relationship between intestinal health and immune aging, emphasizing how gut barrier dysfunction and microbial imbalances accelerate systemic inflammation and diminished immune function. Furthermore, we explore the effects of aging on intestinal barrier function, focusing on the decline in tight junction integrity, reduced mucus production, and impaired epithelial renewal, all of which contribute to increased gut permeability and chronic inflammation. Thus, restoring microbial diversity, supporting mucosal defenses, and addressing gut permeability are essential strategies to break this cycle and promote healthy aging. Topics: 1. Introduction: Immune Aging - Immune aging: a decline in immune function, increasing vulnerability to infections and chronic diseases. - The intestinal microbiome influences and is shaped by immune aging. - Microbial metabolites, epithelial integrity, and immune signaling are critical. 2. Anatomical Context of the Gut and Immune Cells - Gut layers: lumen, mucus, epithelium, lamina propria, and more. - The mucus layer protects the epithelium; function can become impaired with age. - Tight junctions prevent pathogen entry, while the lamina propria houses immune cells. 3. Mucus Layer and Goblet Cells: Role and Aging Effects - Goblet cells secrete mucins that form the protective mucus layer. - Aging can reduce mucin production, weakening the mucus barrier. - A thin mucus layer increases epithelial exposure and inflammation risk. 4. Microbial Interactions with the Mucus Layer - Commensal bacteria support mucus turnover by controlled mucin degradation. - Dysbiosis can disrupt this process, thinning the mucus layer. - Reduced mucus protection increases susceptibility to pathogens. 5. Effects of Immune Aging on the Intestinal Barrier - Aging effects on T cells, B cells, and inflammatory cytokine secretion. - Cytokines disrupt tight junctions and increase permeability. - Microbial products like LPS (endotoxin) cross the barrier, fueling chronic inflammation. 6. Dysbiosis and Its Role in Immune Aging - Dysbiosis reduces SCFA production and Treg activity. - Dysbiosis promotes chronic inflammation and accelerates immune aging. 7. Microbial Translocation and Systemic Effects - A weakened barrier allows microbial products to reach immune cells. - LPS triggers inflammatory signaling, amplifying systemic inflammation. - Chronic inflammation perpetuates gut dysfunction and immune aging. 8. Conclusion - Immune aging and intestinal health are interconnected in a feedback loop. - Aging weakens the gut barrier, while dysbiosis amplifies inflammation. - Restoring microbial balance and gut integrity is vital for healthy aging. Thanks for tuning in! "⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠75 Gut-Healing Strategies & Biohacks⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠" Follow Chloe on Instagram ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Follow Chloe on TikTok @chloe_c_porter Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠synthesisofwellness.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support

Treg and Vicky discuss everything you need to know about bone stress injuries including how to determine if you have one, treatment protocols, and prevention tips!

Treg and Vicky discuss their recent race experiences which leads them down a path of discussing important topics like how determine if you're fueling enough and what to do when those negative thoughts hit during a race.

durée : 00:27:22 - Le Feuilleton - Ayden, Liv et Od' font route vers l'Académie des druides. Lorsque leur maître Tregòn s'absente, ils décident de faire escale dans une étrange auberge perdue au milieu de la forêt. Mais ils ignorent encore que ce lieu cache un terrible secret…

durée : 00:27:22 - Le Feuilleton - Ayden, Liv et Od' font route vers l'Académie des druides. Lorsque leur maître Tregòn s'absente, ils décident de faire escale dans une étrange auberge perdue au milieu de la forêt. Mais ils ignorent encore que ce lieu cache un terrible secret…

Håkon og David har reist til Tyskland for å teste Opels nye Model Y-konkurrent, som har plass til vaskemaskin i bagasjerommet og kommer med monsterrekkevidde. Men går nye Grandland for sakte? Hosted on Acast. See acast.com/privacy for more information.

Treg and Vicky discuss piriformis syndrome and hamstring tendinopathy in today's episode. This discussion starts at 18:23 after Treg and Vicky recap their weeks.

Treg and Vicky continue the common running injury series today discussing patellar tendinopathy and ITB pain in runners.

I ftuar në “Live From Tirana” ka qenë artisti më i ri i tregut, Eko. Ai ka publikuar këngën e tij më të re të titulluar “Prej që t'kom lon” që është bërë këtë jave pjesë e “The Top List”. Po ashtu ai ka nxjerrë dhe EP-n e tij “9 Minuta Ego” për të cilën ka folur më shumë…

Treg and Vicky discuss the first topic in the new "common running injury" series where each week they will review different injuries that most runners experience. Vicky will put up a question box on her instagram each week so check there if you have specific questions! Today is on the plantar fascia, achilles tendon and post tib pain.

Why You Should Listen:  In this episode, you will learn about the use of GENIE testing in Chronic Inflammatory Response Syndrome. About My Guest: My guest for this episode is Dr. Ritchie Shoemaker.  Ritchie Shoemaker, MD is a recognized leader in patient care, research, and an education pioneer in the field of biotoxin related illness.  While illness acquired following exposure to the interior environment of water-damaged buildings (WDB) comprises the bulk of Dr. Shoemaker's daily practice, other illnesses caused by exposure to biologically-produced toxins are quite similar in their “final common pathway.”  What this means is that while the illness might begin acutely with exposure to fungi, spirochetes, apicomplexans, dinoflagellates and cyanobacteria, for example, in its chronic form, each of these illnesses has similar symptoms, lab findings, and Visual Contrast Sensitivity (VCS) findings.  Taken together the inflammatory illness from each of these diverse sources is known as  Chronic Inflammatory Response Syndrome. Key Takeaways: What is GENIE? Is HLA-DR still relevant? What are the common triggers of CIRS?  Actinobacteria?  Endotoxins?  Mold and mycotoxins? What is hypometabolism? How does CIRS impact insulin and blood sugar? What is apoptosis? What is the role of coagulation in CIRS? Are upregulated cytokines seen in CIRS? Can GENIE identify those that may have Lyme? What are defensins? What is Ikaros? What is the role of MAP kinases in CIRS? What do Toll receptors tell us? How are B and T cells involved in CIRS? How many CIRS markers are needed in GENIE to suggest CIRS? What is the PTSD gene? How often is histamine involved? What are the cytoskeleton and microtubules?  What can be determined around the function of Treg cells? What are the recent additions to GENIE in the realm of Parkinson's disease? What has GENIE told us about MARCoNS? Connect With My Guest:  http://SurvivingMold.com Interview Date: September 11, 2024 Transcript: To review a transcript of this show, visit https://BetterHealthGuy.com/Episode205. Additional Information: To learn more, visit https://BetterHealthGuy.com. Disclaimer:  The content of this show is for informational purposes only and is not intended to diagnose, treat, or cure any illness or medical condition. Nothing in today's discussion is meant to serve as medical advice or as information to facilitate self-treatment. As always, please discuss any potential health-related decisions with your own personal medical authority. 

In this episode, we dive into how short-chain fatty acids (SCFAs), particularly butyrate, and tryptophan metabolites support the gut-immune axis by promoting regulatory T cell differentiation, strengthening the intestinal barrier, and enhancing antimicrobial defenses through IL-22 signaling. We break down how butyrate can improve immune tolerance as well as epithelial integrity, aiding in the prevention of chronic inflammatory responses. We also detail practical ways to support butyrate levels and aid in strengthening both the epithelial barrier and gut-immune axis. Topics: 1. Introduction - Overview of the role of SCFAs and tryptophan metabolites in supporting the gut-immune axis. - Quick review of the location of immune cells in relation to the gut microbiota. 2. The Intestinal Barrier - Structure of the intestinal wall and layers - Focus on the mucosal layer, specifically epithelium and lamina propria. 3. The Lamina Propria - Structural elements: fibroblasts, extracellular matrix (ECM), and myofibroblasts. - Vascular components: endothelial cells, capillaries, and lymphatic vessels. - Importance of the lamina propria as a hub for immune responses. 4. Immune Cells in the Lamina Propria - T cells: Role of regulatory T cells (Tregs) in immune modulation. - B cells: Production of IgA, class switching, and plasma cells. - Dendritic cells: Sampling luminal antigens and initiating immune responses. - Macrophages: Phagocytic activity, pro-inflammatory (M1) vs. anti-inflammatory (M2) states. - Mast cells: Role in allergic responses, chronic inflammatory conditions, and MCAS. 5. Short-Chain Fatty Acids (SCFAs) - Production of SCFAs (acetate, propionate, butyrate) by gut microbiota. - Butyrate's role in supporting regulatory T cell (Treg) differentiation and immune tolerance. -Butyrate as fuel for epithelial cells and the production of tight junction proteins. 6. Mechanisms of Butyrate in Immune Modulation - Impact on Tregs through FoxP3 expression. - SCFA's role in maintaining immune balance. 7. Butyrate and Epithelial Integrity - Support for tight junction protein expression. - Prevention of translocation of harmful microbes and antigens. - Reduced systemic inflammation through a strengthened barrier. 8. Supporting Butyrate Production - Sodium butyrate supplementation and microbiome optimization. - Role of fiber, polyphenols, and probiotics. 9. Tryptophan Metabolites - Overview of tryptophan metabolism by gut bacteria into indoles. - Indoles' role in promoting IL-22 production, contributing to antimicrobial defense and immune tolerance. 10. IL-22 - IL-22's enhancement of antimicrobial peptides (AMPs) and mucin production. - Case Study: Role of Lactobacillus strains in restoring IL-22 and helping to mitigate colitis. 11. Conclusion - Recap of how SCFAs and tryptophan metabolites interact with the gut-immune axis. - Importance of gut microbiome support for maintaining immune balance. Thank you to our episode sponsor: 1. Check out ⁠⁠⁠⁠Daily Nouri⁠⁠⁠⁠ and use code ⁠⁠⁠⁠CHLOE20⁠⁠⁠⁠ for 20% off your order. Thanks for tuning in! Get Chloe's Book Today! "⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠75 Gut-Healing Strategies & Biohacks⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠" Follow Chloe on Instagram ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Follow Chloe on TikTok @chloe_c_porter Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠synthesisofwellness.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to purchase products, subscribe to our mailing list, and more! --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support

Treg and Vicky answer the rest of the marathon questions from last week's episode, and then discuss best taper strategies to make sure you're prepared for race day!

Treg and Vicky discuss what they learned and defining experiences while training for their respective marathons as well as on race day. A must-listen for anyone who has a marathon on their calendar this fall!

Treg and Vicky discuss their plans for season 2 of the podcast, how they both approached running differently on their summer vacations, and *TW* the tragic passing of Olympic runner Rebecca Cheptegei as well as important conversations around keeping women safe in the running community. If you or anyone you know has experienced domestic abuse please refer to the National Domestic Violence hotline: https://www.thehotline.org/ Additional resources as discussed in our show: Tirop's Angels @tirops_angels on IG

Dr. Lillian Siu and Dr. Melvin Chua discuss the new technologies and novel therapeutics that were featured at the 2024 ASCO Breakthrough meeting. TRANSCRIPT Dr. Lillian Siu: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Lillian Siu, a medical oncologist and director of the Phase 1 Trials Program at the Princess Margaret Cancer Center in Toronto, Canada, and a professor of medicine at the University of Toronto. On today's episode, we'll be discussing key takeaways from the 2024 ASCO Breakthrough meeting in Yokohama, Japan. Joining me for this discussion is Dr. Melvin Chua, who served as the chair of Breakthrough's Program Committee. Dr. Chua is the head of the Department for Head, Neck and Thoracic Cancers in the Division of Radiation Oncology at the National Cancer Center in Singapore. Our full disclosures are available in the transcript of this episode. Dr. Chua, it's great to be speaking with you today and congratulations on a very successful Breakthrough meeting. Dr. Melvin Chua: Thanks Dr. Siu. It was really inspiring to come together again to showcase the innovative work of world-renowned experts, clinicians, researchers, med-tech pioneers, and drug developers from around the globe. Our theme this year was inclusivity and thus it was important to bring people together again in the Asia Pacific region and to foster international collaborations that are so important in advancing cancer care. This year, we invited 65 international faculty, of which 55% were from Asia. Also, importantly, we achieved approximately a 50-50 split for male to female representation. These are remarkable statistics for the meeting, and we really hope to retain this for future Breakthrough [meetings]. Dr. Lillian Siu: The meeting featured renowned keynote speakers who shared great insights on new technologies and therapies that are shaping the future of drug development and care delivery. Let's first talk about artificial intelligence and the keynote address by Dr. Andrew Trister. He gave a very interesting talk titled, “Plaiting the Golden Braid: How Artificial Intelligence Informs the Learning Health System.” What are the key messages from his talk? Dr. Melvin Chua: Couldn't agree with you more, Dr. Siu. Dr. Trister is the chief medical and scientific officer of Verily, a precision health company. He previously worked in digital health and AI at The Bill and Melinda Gates Foundation, and worked at Apple where he led clinical research and machine learning with Apple partners. But perhaps it was really his background and training as a radiation oncologist that was most pertinent as he was able to weave both the components of new AI models and the applications and pitfalls in the clinic to the audience. Dr. Trister provided a very high-level view through the history of AI and showcased the progression of the different AI models and he basically explained between deep and shallow methods as well as deductive logic versus inductive probabilistic methods. He then provided several clinical examples where these models have shown their utility in the clinic, for example, pathology and so forth. At the same time, he illustrated several pitfalls with these models. So overall, I think Dr. Trister's talk was very well received by the audience with several key messages, including the importance of [using] high-quality data as the basis of a good AI model. AI was also addressed in an Education Session that looked at Artificial Intelligence in the Cancer Clinic. And we had a panel of experts that highlighted current progress and successes with AI in the clinic, advances with AI assisted pathology for clinical research and precision medicine, large language models (LLMs) for applications in the clinic, and how we could leverage AI in precision oncology. And from this session, I had several key takeaways. Dr. Alexander Pearson [of the University of Chicago] gave a very illustrative talk on how multimodal information across clinical omics, radiological information and multi omics could be used to improve diagnostic tasks and clinical prediction across different cancers. And Dr. Joe Yeong [of Singapore General Hospital] gave a very good talk on how AI can be applied in digital pathology to accelerate research in immunology and help in the development of immunotherapies. Dr. Danielle Bitterman [of Brigham and Women's Hospital] shared very good examples of how LLMs could be used in a clinic. And I think the example that really stood out for me was how LLMs could be deployed to create responses to patient queries. And of course, the big question in the room was: How could AI eventually encapsulate compassion in their response? I think this again showcased how LLMs could really help to accelerate our clinical work going forward. And ultimately circling back to data, Dr. Caroline Chung [of MD Anderson] gave a very poignant description on the importance of data quality and how poor-quality data could eventually lead to underperforming AI models. So all in all, I think this was a great session. And what do you think, Dr. Siu? Dr. Lillian Siu: Melvin, I totally agree with you. I like all your comments and I really enjoyed the keynote as well as the session on AI in the cancer clinic chaired by Dr. Pearson. I think all these sessions were really informative. Discussions on the latest AI and machine learning, algorithms and technologies on digital pathology, LLMs and big data, as you said, really enables the attendees, especially clinicians like me, to gain a deep understanding of how AI can be translated to practical applications. Dr. Melvin Chua: Great. So, Dr. Siu, let's talk about some of the novel therapeutics that were featured at the meeting. Again, this was an important session for Breakthrough, and it's always been there. So could you share some highlights from the sessions on novel drug development from your perspective? Dr. Lillian Siu: Yes, indeed. Drug development is such an exciting aspect of this meeting. On Day 3 of the meeting, we had a keynote by Dr. Shimon Sakaguchi of Osaka University, who discussed “Targeting Regulatory T cells (Tregs) in Cancer: The Science, Trials, and Future.” And he talked about T cells, especially Treg biology, the role of Tregs in immune regulation, new developments in Treg immuno-oncology drugs, and how we can actually target Tregs to treat early cancers, etc. This talk is particularly exciting because there are now anti CCR8 antibodies in the clinic that specifically target Tregs, and some early signals of anti-tumor activities are already being observed. Dr. Sakaguchi also emphasized the importance of combination sequence and timing of drugs for the successful use of cancer immunotherapeutic agents. I also want to emphasize the Education Session that followed, titled, “The Future of Immunotherapy, New Drugs and New Ideas.” In that particular session, we heard about engineering T-cell immunity to eradicate tumors. We heard about CAR T-cell therapy in GI cancers, novel immunotherapeutic combinations, and T-cell engagers, which are bispecifics in cancer. While success with some of these immunotherapeutic modalities, such as cell therapies and T-cell engagers have been largely seen in hematological malignancies, we are beginning to observe efficacy signals in solid tumors. For example, the CAR T targeting Claudin18.2 in gastrointestinal cancers and the recently approved FDA-approved DLL3/CD3 bispecific T-cell engager, tarlatamab, in small cell lung cancer are really exciting examples. We also heard from investigators who are exploring neoadjuvant therapies in the neoadjuvant therapy session, and the key takeaway from that session is that we have growing interest in using neoadjuvant therapy or perioperative therapy. In other words, neoadjuvant plus adjuvant therapy in different cancers. In the neoadjuvant session, there were updates provided by different experts on the roles of neoadjuvant therapy in melanoma, liver cancer, bladder cancer, and nasopharyngeal cancer. Increasingly, there is randomized trial evidence to support the use of neoadjuvant therapy or perioperative immunotherapy in several cancer types with survival-based endpoints. Very exciting indeed. Dr. Melvin Chua: Indeed, I couldn't agree with you more. I think one of the things that went into designing the case-based discussions this year was that we wanted to talk about cancers that were relevant to this part of the world and hence we again showcased lung cancers, gastric cancers and melanomas, and whereby we have again perspectives from an expert from the West coupled to an expert from the East, thereby showcasing the diversity of practice around the world. The other thing that we did this year was we decided to pair the case-based discussions with the keynotes and the Education Sessions as well. For example, on Day 3, we had Dr. Sakaguchi speak on Tregs, as you mentioned. And this was followed by an in-depth session on new immunotherapies, and then followed by a case-based discussion on different melanoma cases on the role of neoadjuvant immunotherapy in this disease, and the strikingly relevance of response to prognostication. This is an important trait that we're seeing now that seems to pan out across different cancers, where we find that neoadjuvant response to combination systemic therapies and/or radiotherapy is a strong prognosticator. Dr. Lillian Siu: So, Dr. Chua, we've discussed some breakthrough treatments and promising advances in cancer care, and we've touched upon some barriers to success in cancer treatment. I would like to ask you about the keynote address by Dr. Raffaella Casolino of the World Health Organization, who spoke passionately about efforts by the WHO and its partners to build equity in cancer care. Can you share some highlights with us? Dr. Melvin Chua: Absolutely, Dr. Siu. In spite of the tremendous advances we've seen in recent years in oncology, there are still major disparities in cancer care, such as cost and access, which affect patients worldwide. I think Dr. Casolino's talk was a very nice overview whereby she showed, first of all, the WHO's impact in terms of the WHO Cancer Resolution initiative that was implemented in 2017, where through this initiative, WHO has impacted 100 countries, invested $1 billion in funds, and that has led to millions of lives saved. But she then really drilled down to some of the key examples of the focus of the WHO in terms of equalizing care in cancer. I think one which struck me was the appreciation of the disparities in the clinical trials landscape. I think it is clear that there's still a huge barrier to clinical trials between the high- and middle-income countries and the low- and middle-income countries, and the majority of clinical trials these days are industry sponsored and we really need to look at leveling the playing field in this regard. Then she highlighted the WHO's work on trying to lower the barriers to precision oncology. And I think there are several issues in that sense, but I think what the WHO has really worked hard on is promoting education for genomic medicine, where they've done several reviews with experts around the world to educate the field across the world on how we interpret and apply genomics in the clinic. So all in all, it was very interesting to hear Dr. Casolino's insights from a policy perspective, and again, this emphasizes that there's so much work to be done at the end of the day and the dialogue needs to continue. We also heard about policy, academic and industry perspectives in the context of clinical trials, and that led to a discussion on real-world evidence generation for regulatory approvals. It was very nice that we had a session on that at the end of Breakthrough 2024 (Real-World Evidence and Clinical Trials: Beyond the Ivory Tower). And in that session, we heard from Dr. Shaalan Beg [of the NIH], and Dr. Janet Dancey [of Queen's University] who represented views from academia and Dr. Hidetoshi Hayashi [of Kindai University Hospital] shared perspectives on decentralized trials. I'd like to encourage our listeners to watch these sessions if they were unable to attend. The content is very rich, and I'm sure they'll learn from it. Dr. Lillian Siu: Thank you so much, Dr. Chua. Is there anything else you would like to cover before we wrap up the podcast today? Dr. Melvin Chua: Thank you, Dr. Siu. The thing I really want to emphasize is, apart from all these Educational Sessions and having very eminent keynote speakers, one of the key points that we really want to bring out for Breakthrough is to showcase the high-quality research. This year we had 300 abstracts submitted and they were all high quality, cutting across trials, omics research, AI and technology, and eventually we selected 235 of them and we were able to showcase some of them across three oral sessions over three days. I think this is an important component of Breakthrough that we really wish to continue building upon where people are now excited to use this forum to present their work. Dr. Lillian Siu: Thank you so much, Dr. Chua. I really enjoyed our discussions today. I look forward to seeing how the Breakthrough meeting will continue to grow in future years. Dr. Melvin Chua: Thank you again, Dr. Siu. Thank you for all your leadership and efforts in making Breakthrough a successful meeting series the past few years. Dr. Lillian Siu: Thank you to our listeners for your time today. You'll find links to the session discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcast. Thank you.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:   Dr. Lilian Siu  @lillian_siu  Dr. Melvin Chua  @DrMLChua    Follow ASCO on social media:    @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:   Dr. Lillian Siu:  Leadership (Immediate family member): Treadwell Therapeutics  Stock and Other Ownership Interests (Immediate family member): Agios    Consulting or Advisory Role: Merck, AstraZeneca/MedImmune, Roche, Voronoi Inc., Oncorus, GSK, Seattle Genetics, Arvinas, Navire, Janpix, Relay Therapeutics, Daiichi Sankyo/UCB Japan, Janssen, Research Funding (Institution): Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Merck, Novartis, Pfizer, AstraZeneca, Boehringer Ingelheim, Bayer, Amgen, Astellas Pharma, Shattuck Labs, Symphogen, Avid, Mirati Therapeutics, Karyopharm Therapeutics, Amgen   Dr. Melvin Chua:  Leadership, Stock and Other Ownership Interests: Digital Life Line  Honoraria: Janssen Oncology, Varian  Consulting or Advisory Role: Janssen Oncology, Merck Sharp & Dohme, ImmunoSCAPE, Telix Pharmaceuticals, IQVIA, BeiGene  Speakers' Bureau: AstraZeneca, Bayer, Pfizer, Janssen   Research Funding: PVmed, Decipher Biosciences, EVYD Technology, MVision, BeiGene, EVYD Technology, MVision, BeiGene  Patents, Royalties, Other Intellectual Property: High Sensitivity Lateral Flow Immunoassay for Detection of Analyte in Samples (10202107837T), Singapore. (Danny Jian Hang Tng, Chua Lee Kiang Melvin, Zhang Yong, Jenny Low, Ooi Eng Eong, Soo Khee Chee)    

Það gengur hægt að vinda ofan af verðbólgunni sem er þó komin undir 6% í fyrsta sinn um langt skeið - þingkosningar standa fyrir dyrum í Frakklandi og sumir telja að valið standi milli pestar og kóleru- þessa dagana eru nemendur í skólastofum Háskólans á Akureyri yngri en allajafna. Tregbreytanleg er orðið sem greiningardeildir bankanna nota til að lýsa þróun hennar næstu mánuði. Róbert Farestveit, hagfræðingur hjá ASÍ segir húsnæðismarkaðinn sökudólginn og sá vandi verði ekki leystur með vaxtastigi heldur aðgerðum.

Dr. Diwakar Davar and Dr. Jason Luke discuss advances in the neoadjuvant immunotherapy space that were presented at the 2024 ASCO Annual Meeting, including promising outcomes in high-risk melanoma from the NADINA trial, as well as other new treatment options for patients with advanced cancers.    TRANSCRIPT Dr. Diwakar Davar: Hello and welcome to the ASCO Daily News Podcast. I'm your guest host, Dr. Diwakar Davar, and I am an associate professor of medicine and the clinical director of the Melanoma Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. I am delighted to have my colleague and friend Dr. Jason Luke on the podcast today to discuss key late-breaking abstracts and advances in immunotherapy that were presented at the 2024 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the associate director of clinical research, and the director of the Cancer Immunotherapeutic Center at the University of Pittsburgh Hillman Cancer Center.   You will find our full disclosures in the transcript of this episode.  Jason, it's always a pleasure to hear your insights on the key trials in these spaces and to have you back as a guest on this podcast that highlights some of the work, especially advances, that were just presented. Dr. Jason Luke: Well, thanks very much for the invitation. I always love joining the podcast. Dr. Diwakar Davar: We'll start very quickly by talking about some advances and really interesting things that happened both in the context of melanoma but also in immunotherapy in general. And we'll start with what I think was certainly one highlight for me, which was LBA2, the late-breaking abstract on the NADINA trial. It was featured in the Plenary Session, and in this abstract, Dr. Christian Blank and colleagues reported on the results of this phase 3 trial of neoadjuvant ipi-nivo. This is the flipped dose of ipi1/nivo3 versus adjuvant nivolumab in PD-1 naive, macroscopic, resectable, high-risk stage 3 melanoma.  By way of background, neoadjuvant immunotherapy for those listening is an area of increasing interest for drug developers and development for both approved and novel agents. Neoadjuvant immunotherapy has been studied with multiple approved agents, including PD-1 monotherapy, PD-1 LAG-3, PD-1 CTLA-4, T-VEC, as well as investigational agents and multiple randomized and non-randomized studies. The benchmark pathologic response rates with these agents range from 17% PCR with PD-1 monotherapy, 45% to 55% PCR with PD-1 CTLA-4 combination therapy, and slightly higher 57% PCR with PD-1 LAG-3 has recently reported by Dr. Rodabe Amaria from MD Anderson. However, as we embark on phase 3 comparisons for various neoadjuvant compared to adjuvant immunotherapy trials and combinations, we're increasingly moving towards event-free survival as the primary endpoint for neoadjuvant versus adjuvant studies. And this was most recently studied in the context of SWOG S1801, a study that was led by Dr. Sapna Patel.  So, Jason, before we start on NADINA, can you briefly summarize the SWOG S1801 trial and the event-free survival statistic reported by Dr. Patel and her colleagues? Dr. Jason Luke: Well, absolutely. And these data were reported at ESMO about two years ago and then in the New England Journal last year. The S1801 study answered a very simple question: What would happen if you took three of the doses of standard adjuvant therapy with pembrolizumab and moved them prior to surgery? And on a high level, the study is as simple as that. And many of us were somewhat skeptical of this trial design because we thought that just moving the doses earlier may not actually have a major impact.  In the study, you alluded to the event-free survival statistic, and that alludes to what was considered an event. And so, without reading all of it, there were several different aspects that were included in terms of time, based on the date of randomization until the first of a series of events, such as disease progression, toxicity from treatment, if the patient was unable to go to surgery or had surgical complications, or if they had delay in starting the adjuvant therapy due to toxicity, and obviously, recurrence of melanoma or death from any cause. In that context, merely moving the 3 doses of pembrolizumab to the neoadjuvant setting saw an improvement in this two-year event free survival to 72% for the neoadjuvant therapy compared to 49% for the adjuvant therapy. That was quite an outstanding change. And again, noting the power of neoadjuvant treatment, really dictating the impact of anti PD-1, again, just with 3 doses moving from adjuvant into the neoadjuvant setting, and I think all of us were somewhat surprised to see that magnitude of a benefit. But it set up the current study very well, where we now look at combination therapy. Dr. Diwakar Davar: So let's move on to the phase 3 NADINA trial. Do you want to perhaps discuss the study design, particularly focusing on the EFS primary endpoint and maybe also touching on the different schedules? So, SWOG S1801 was a neoadjuvant study of 3 cycles of pembrolizumab and how did that compare and contrast to the neoadjuvant combination that was studied in NADINA? Dr. Jason Luke: Well, as you alluded to, NADINA investigated the regimen of nivolumab plus ipilimumab and compared that against adjuvant therapy with nivolumab alone. So, in the study, as you alluded, the dose and schedule of the two drugs used was nivolumab at 3 milligrams per kilogram, and ipilimumab with 1 milligram per kilogram. That was based on a series of signal finding and safety studies that had been previously done by the same group of authors identifying that as the optimal treatment regimen. And it's worth noting that's slightly different than the labeled indication that's generally used for those same drugs for metastatic melanoma, albeit that the NCCN also endorses this schedule. So, in the trial, 423 patients were randomized, 1:1 to receive either neoadjuvant therapy with those 2 doses of nivolumab plus ipilimumab as compared with standard adjuvant therapy with nivolumab following surgery.   Now, one interesting tweak was that there was an adaptive nature to the study, meaning that patients had a fiducial placed at the index lymph node, and after the neoadjuvant therapy in that arm, that lymph node was removed. And if the patient had a major pathological response, they did not go on to receive the adjuvant portion of the treatment. So it was adaptive because those patients who did very well to the neoadjuvant did not require the adjuvant portion. And in those patients who did not achieve a major pathological response, they could go on to have the adjuvant therapy. And that also included the BRAF therapy for those whose tumors were BRAF mutants.  It's also worth pointing out that the definition of event free survival was slightly different than in the S1801 study that was alluded to just a second ago. And here, EFS was defined from the date of randomization until progression due to melanoma or due to treatment. So that's slightly different than the definition in the S1801 trial. So, a somewhat complicated study, but I really applaud the authors because I think this study does mirror what we would likely be doing in actual clinical practice.  Dr. Diwakar Davar: So, just to briefly summarize the efficacy, and then to get your comments on this, the path response, the PCR rate was 47%. The major pathologic response rate, which is the proportion of patients with between 0% to 1/10% of residual viable tumors, was about 12%. And for a major pathologic response rate of 0% to 10% of 59%. And then the rest of the patients had either pathologic partial response, which was 10% to 50%, or pathologic non response or 50% or greater residual viable tumor, all assessed using central pathology grades. The one year RFS was 95% in the FDR patient population versus 76% in the pathologic partial response patient population, 57% in the pathologic non response patient population. So how do you view these results? Can you context the FDR rates and the EFS rates from NADINA relative to nivo-rela and also potentially SWOG 1801? Dr. Jason Luke: Well, I think these are very exciting results. I think that for those of us that have been following the field closely, they're actually not especially surprising because they mirror several studies that have come before them. When we put them in context with other studies, we see that these rates of major pathological response are consistent with what we've seen in phase 2 studies. They're relatively similar. Or I should say that the results from nivolumab and relatlimab, which was also pursued in a phase 2 study of somewhat similar design, are somewhat similar to this. So, combination immunotherapy does look to deliver a higher major pathological response than pembrolizumab alone, as was known in S1801. Which of course, the caveat being is these are cross control comparisons that we need to be careful about. So I think all of these are active regimens, and I think adding a second agent does appear to enhance the major pathologic response rates. When we look at the event free survival, we see something similar, which is that numerically it looks to be that combination immunotherapy delivers a higher event free survival rate. And that looks to be rather meaningful given the difference in the hazard ratios that were observed between these various studies. And here in the NADINA study, we see that 0.3 hazard ratio for EFS is just extremely impressive.  So the abstract then, from ourselves, out of these specific studies, what does this mean more broadly in the real world, where patients exist and the rest of the landscape for clinical trials? I think we can't take enough time to stop for a second and just think about what a revolution we've come forward in with immune checkpoint blockade and melanoma. When I started my career, now, more than 15 years ago, melanoma was the cancer that made cancer bad. And now here we say, in the highest risk of perioperative patients, we can deliver 2 doses of nivolumab and ipilimumab, and essentially half of the patients then don't need to go on, and more than half the patients don't need to go on to have a full surgery and don't need adjuvant therapy. And from what we could tell of a very, very low risk of every heavy recurrence of melanoma. Of course, there's the other half of patients where we still need to do better, but these are just fantastic results and I think highly meaningful for patients.   In the context of ongoing clinical trials, another abstract that was presented during the meeting was the update to the individualized neoantigen therapy, or V940 with pembrolizumab or against pembrolizumab alone. That's the KEYNOTE-942 study. In that study, they presented updated data at two and a half years for relapse free survival, noting a 75% rate without relapse. So those results are also highly intriguing. And these are in a similar population of very high risk patients. And so I think most of us believe that neoadjuvant therapy with this study in NADINA is now confirmed as the priority approach for patients who present with high-risk stage 3 disease. So that would be bulky disease picked up on a scan or palpable in a clinic. I think essentially all of us now believe patients should get preoperative immunotherapy. We can debate which approach to take, and it may vary by an individual patient's ability to tolerate toxicity, because, of course, multi agent immunotherapy does have increased toxicity relative to anti PD-1 alone. But we'll have to wait now for the full phase 3 results from the V940 individualized neoantigen therapy. And if those come forward, that will be an extremely attractive approach to think about for patients who did not achieve a major pathological response to neoadjuvant therapy, as well as of course to the other populations of patients with melanoma where we otherwise currently give adjuvant therapy stage 2B all the way through stage 4 resected. It's an amazing time to think about perioperative therapy in melanoma. Dr. Diwakar Davar: So this is clearly outstanding data, outstanding news. Congratulations to the investigators for really doing what is an investigative initiated trial conducted across multiple continents with a huge sample size. So this clearly appears to be, at this point in time at least, a de facto standard. But is this going to be FDA-approved, guideline-approved, or is it possible in your mind? Dr. Jason Luke: Well, that's an interesting question. This study was not designed with the intent to necessarily try to register this treatment regimen with the FDA. One would have to take a step back and say, with how powerful these data appear, it sort of seemed like it would be too bad if that doesn't happen. But all the same, I think the community and those of us who participate in guideline recommendations are fully supportive of this. So, I think we will see this move into compendium listings that support insurance approval, I think, very, very quickly. So, whether or not this actually becomes formally FDA approved or is in the guidelines, I think this should become the standard approach that is considered for patients, again presenting with high-risk stage 3 disease.  Dr. Diwakar Davar: Fantastic. So now we're going to go in and talk about a slightly different drug, but also from the melanoma context, and that is the safety and efficacy of RP1 with nivolumab in the context of patients with melanoma who are PD-1 failures. So, this is Abstract 9517. And in this abstract, our academic colleagues essentially talked about these data, and we'll start by describing what RP1 is. RP1 essentially is a HSV-1 based oncolytic immunotherapy. And RP1 expresses GM-CSF as well as a fusogenic protein, GALV-GP-R-. And in this abstract, Dr. Michael Wong from MD Anderson and colleagues are reporting the results of IGNYTE, which is a phase I trial of intratumoral RP1 co-administered with systemic nivolumab in patients with advanced metastatic treatment refractory cutaneous melanoma. And the data presented in this abstract represents data from a registration directed, abbreviated as RD, registration directed cohort of RP1 plus nivolumab in PD-1 refractory melanoma. So, let's start with the description of the cohort.  Dr. Jason Luke: Right. So, in this study, there were a total of 156 patients who were presented, and that included an initial safety and dose finding group of 16, as well as the RD cohort, as you noted, of 140 patients. And it's important to point out that this was a cohort that was selected for a very strict definition of progression on anti PD-1, or a combination immunotherapy as their immediately prior treatment. So, all of the patients in the cohort had exposure to anti PD-1, and 46% of them had anti PD-1 plus anti CTLA4, nivolumab and ipilimumab as their immediately prior therapy. This was also a group of relatively high-risk patients when one considers stage. So, within the stage 4 population, the entry here included 51% who had stage M1B, C, and D melanoma. And that is worth pointing out because this is an injectable therapy. So, trials like this in the past have tended to be biased towards earlier stage, unresectable or metastatic melanoma, meaning stage 3B, 3C, 3D and then stage 4m1a. Again, to emphasize the point here, these were pretreated patients who had a strict definition of anti PD-1 resistance, and over half of them, in fact, had high-risk visceral metastatic disease.  In that context, it's very interesting to observe that the overall response rate was described in the total population, as 31%, and that included 12% who achieved complete response. And so, again, to make sure it's clear, we're talking about a treatment where the oncolytic virus is injected into one or multiple sites of recurrent disease, and then the patients administer nivolumab as per standard. And so, I think these data are quite intriguing. Again, such a high- risk population and their maturity now, with a follow-up of over a year, I think, makes this look to be a very interesting treatment option.  Dr. Diwakar Davar: I guess on that topic of mature follow-up, it probably would be important for us to inform our audience that the top line data for the primary analysis was actually just released, I think, earlier today, and wherein the central confirmed objective response rate was 34% by modified RECIST and 33% by RECIST, clearly indicating that these responses, as you noted, very treatment refractory patient population, these responses were clearly very durable. So, you mentioned that there were responses seen in uninjected visceral lesions, responses seen in both PD-1 and PD-1 CTLA-4 refractory patients. Can you talk a little bit about the response rate in these high-risk subgroups, the uninjected visceral lesions, the patients who had both combination checkpoint and epidural refractory response rate by primary PD-1 resistance.  Dr. Jason Luke: Sure. You know, I think, again, to emphasize this point in the study, we saw that there were responses in the non-injected lesions, and I think it's really important to emphasize that. Some have referred to this as a putative abscopal like effect, similar to what is described in radiation. But it implies that local treatment with the oncolytic virus is triggering a systemic immune response. In the higher risk patient population, we'll note that whereas the overall response rate in PD-1 refractory patients was 34%, in the combination of PD-1 and CTLA-4 refractory patients, the response rate was 26%. So, [this is] still very good. And when we looked at that split by stage, as I alluded to before, in the population of patients that had, what you might call earlier unresectable diseases, so 3B through 4A, the response rate was 38%, and in the stage 4 M1b through M1d, it was 25%. So slightly lower, but still very good. And that would be as expected, because, of course, the patients with visceral metastatic disease have more advanced disease, but those response rates look quite good. Again, looking at the combination refractory population as well as the more high-risk disease. Dr. Diwakar Davar: So, clearly, these are very promising data and exciting times for multiple investigators in the field and the company, Replimune, as well. So, what are the next steps? I believe that a registration trial is planned, essentially, looking at this with the goal of trying to get this combination registered. Can you tell us a little bit about IGNYTE-3, the trial design, the control arm, and what you foresee this trial doing over the next couple of years?  Dr. Jason Luke: So, as this agent has been maturing, it's worth pointing out that the company that makes this molecule, called RP1, but I guess now we'll have to get used to this name vusolimogene oderparepvec as the actual scientific term, they have been having ongoing discussions with the FDA, and there is the potential that this agent could come forward on an accelerated path prior to the results being released from a phase 3 trial. That being said, the phase 3 confirmatory study, which is called the IGNYTE-3 study, is in the process of being launched now. And that's a study investigating this molecule in combination with nivolumab, as was alluded to earlier, and a randomized phase 3 design, where that combination is compared with a physician's choice, essentially a chemotherapy-based option.   In that study, it will be 400 patients with stage 3B through stage 4; patients will have progressed on anti PD-1, either as a combination or in sequence, and then come on the study to be randomized to either vusolimogene oderparepvec plus nivolumab versus that physician's choice. And the physician's choice includes chemotherapy agents, but also nivolumab plus relatlimab as another option, or an anti PD-1 monotherapy, if that's deemed to be a reasonable option by the treating investigator. And the primary endpoint of that study is overall survival. And unfortunately, in this highly refractory patient population, that's something that may not take long to identify with key secondary endpoints of progression free survival, as well as overall response rate. I'm quite enthusiastic about this study, given these data, which have now been centrally confirmed as you alluded to before. I think this is a very exciting area of investigation and really crossing my fingers that this may be perhaps the first locally administered therapy which does appear to have a systemic impact that can hold up in phase 3. Dr. Diwakar Davar: Very, very, very exciting results. And I guess it's worthwhile pointing out that this company also has got, I think, multiple studies planned with both RP1 and cutaneous squamous cell carcinoma in a solid organ transplant patient population where single agent activity has already been reported by Dr. Migden at prior meetings, as well as a novel trial of potentially RP2 metastatic uveal melanoma. So we'll now pivot to Abstract 6014. So, 6014 is a drug by a company known as Merus. Essentially, it's a very novel agent. Merus essentially is a company that is specialized in making bicyclics and tricyclics. And these are not bicycles or tricycles, but rather drugs that essentially are bispecific antibodies. And Merus essentially has come up with petosemtamab. I think we're going to have to figure out better names for all of these drugs at some point. But petosemtamab, or MCLA-158, essentially is a bicyclic, targeting both EGFR as well as LGR-5. So EGR-5, of course, is a known oncogenic driver in multiple tumor types, squamous, including non small cell lung cancer, cutaneous squamous cell carcinoma, but also head and neck squamous cell carcinoma. And LGR-5 essentially is leucine-rich repeat-containing G-protein coupled receptor 5, but it's a receptor in cancer stem cells and certainly highly expressed in head neck squam. And MCLA-158, or petosemtamab is a IgG one bispecific with ADCC-activity because of IgG1 backbone co-targeting EGFR and LGR5. Merus had earlier results that evaluated petosemtamab monotherapy. They defined the RP2D and second- and third-line head and neck blastoma patients with a respectable response rate of 37% investigator-assessed ORR with six months median DoR, and this was published by Ezra Cohen about a year or so ago.  In this abstract, Dr. Fayette and colleagues report on the results of the MCLA-158-CL01 trial, which is a trial of pembrolizumab plus petosemtamab in one front line head and neck squamous cell population. So maybe let's start with the description of the cohort. And it is a small trial, but we'll be able, I think, to dig into a little bit about why this might be exciting. Dr. Jason Luke: Yes. So, as alluded to, it's not the biggest trial as yet, but there were 26 patients with anti PD-1 treatment naive head and neck squamous cell carcinoma. And all the patients in the study did receive, as you alluded to, pembrolizumab plus petosemtamab. Based on the label for pembrolizumab, all the patients in this study were PDL-1 positive. So that's one point that it's worth pointing out to make sure that that's understood. This is the population of patients who would be expected to benefit from pembrolizumab in the first place. Now, in the abstract, they reported out only 10 response evaluable patients, but they updated that in the actual slides of presentation at the meeting. So among 24 patients that were alluded to, 67% were described as having had a response, although some of those were yet to be confirmed responses. And when it was evaluated by PDL-1 status, there didn't seem to be a clear enrichment of response in the PD-1 positive more than 20% group, as compared to the 1-19% group. That isn't especially surprising because that was a trend that one would see, presumably with pembrolizumab alone. But overall, I think these data are pretty exciting in terms of a preliminary study. Dr. Diwakar Davar: You know, you mentioned that the objective response rate was high, almost 60-something%. The prognosis of these patients is generally poor. The OS is typically thought of as between 6-15 months. And based on KEYNOTE-048, which was led by Dr. Burtness and colleagues, the standard of care in the setting is pembrolizumab +/- platinum based chemotherapy regimens. Allowing for the fact that we only have 10 patients here, how do you think these results stack up against KEYNOTE-048? And you made a very important point earlier, which was, by definition, pembro is on label only for the CPS. So PDL-1 score, at least in head and neck squamous cell carcinoma CPS and not TPS. But in the CPS 1% or greater patient population, where pembro is on label, how do these results stack up against the KEYNOTE-048 results. Dr. Jason Luke: Right. KEYNOTE-048 is considered the seminal study that dictates frontline treatment in head and neck cancer. And before we dive into this too far, we do want to acknowledge that here we're comparing 26 patients versus a phase 3 trial. So, we're not trying to get too far ahead of ourselves, but this is just a preliminary comparison. But in KEYNOTE-048, as you alluded to, two regimens were superior to chemotherapy. One was the pembrolizumab monotherapy, as well as pembrolizumab plus chemotherapy. So again, the study overall survival, of course, was much higher, the PDL-1 positive subgroup, which is what dictated the unlabeled use of this. But response to pembro monotherapy in that population of patients is still modest. We're talking about upwards of 20-30%. So, if you compare that to, again, preliminary evidence here from this trial of only 24 patients, that response rate of 60% seems extremely high. And so even if that were to come down somewhat in a larger data series of patients, that still looks to be quite promising as a treatment regimen, that might eventually even be chemotherapy sparing for this population of patients. I think this raises a lot of eyebrows that perhaps this dual targeting approach, EGFR and LDR-5, may bring something really important to the field that evolves it. Dr. Diwakar Davar: So, what are the next steps for petosemtamab? You mentioned that the activity was interesting. Are we going to see a larger trial? Any thoughts on where things are going to go?  Dr. Jason Luke: Well, based on the phase 2 data of petosemtamab alone, even without pembrolizumab, the molecule had already been given fast track designation by FDA, which means allowing for greater communication between the drug sponsor in the FDA and designing a seminal study design. One would assume that this trial will be rapidly expanded quite greatly, perhaps to 100 or 200 patients, to try to flush out what the real response rate is in a more meaningful number of patients. But I think these data will probably also trigger the design and probably near-term evaluation or expedited acceleration of a phase III clinical trial design that would potentially validate this against the current standard of care. So, I'm pretty excited. I think we'll see a lot more about this agent in the relatively near future. Dr. Diwakar Davar: So, finally, we'll pivot to the last abstract that we're going to talk about, which is Abstract 2504. It's a relatively interesting target, CCR8 monoclonal antibody. But this is the efficacy and safety of LM-108, and LM-108 is an anti CCR8 monoclonal antibody that is being developed by LaNova Medicine. And the results that are described, actually a pool set of results of combinations of LM-108 with anti PD-1, two separate anti PD-1, in patients with gastric cancer, mostly done ex-U.S., which is interesting because of this patient population, and it's a pool result of several, 3 phase 1 and 2 studies.  LM-108 is an Fc-optimized anti CCR8 monoclonal antibody that selectively depletes tumor infiltrating Tregs. The abstract reported a pooled analysis of three phase 1, 2 trials with 3 different NCT numbers that all evaluated the efficacy of LM-108 and anti PD-1 in patients with gastric cancer. So, let's start with the description of the cohort. Maybe, Jason, you can tell us a little bit about before you start, as you describe the cohort, sort of what we know, editorially speaking, about the difficulty with which Tregs depletion has been tried and obviously failed up until now in the tumor microenvironment. Dr. Jason Luke: Right. I think that's a really interesting comment. And so, for decades, in fact, targeting regulatory T-cell to alleviate immune exclusion in the tumor microenvironment has been of interest in immuno-oncology. And in preclinical mouse models, it seems quite clear that such an approach can deliver therapeutic efficacy. However, by contrast, in human clinical trials, various different Treg depleting strategies have been attempted, and there's really little to no evidence that depleting Tregs from human tumors actually can deliver therapeutic responses. And by that we're referring to CD-25 antibodies. The drug ipilimumab, the CTLA-4 antibody, was punitively described as a Tregs depleter preclinically, but that doesn't seem to be the case in patients. And so, in that background, this is quite an eye raiser that an anti CCR8 antibody could be driving this effect. Now, before we talk about the results of this trial, I will point out, however, that given the Fc-optimization, it's entirely possible that the Tregs are being depleted by this mechanism, but that more could also be going on. Because Fc gamma RII binding by this antibody that could be nonspecific also has the potential to trigger immune responses in the tumor microenvironment, probably mediated by myeloid cells. So I think more to come on this. If this turns out to be the first meaningful Tregs depletor that leads to therapeutic efficacy, that would be very interesting. But it's also possible this drug could have multiple mechanisms.  So, having said all of that, in the clinical trial, which was a pooled analysis, like you mentioned, of LM-108 in combination with anti PD-1 of a couple different flavors, there were 48 patients treated either with LM-108, with pembrolizumab, or with toripalimab, which is another anti PD-1 antibody. On the drug combination was, generally speaking, pretty well tolerated, noting grade 3 treatment related adverse events in the range of 38%, which is somewhat expected given combination immunotherapy. We talked about nivolumab and ipilimumab before, which, of course, gives even higher rates of immune-related adverse events, with the most common toxicities being anemia, lipase elevations, rash, ALC decrease; albeit, quite manageable. Dr. Diwakar Davar: So, what about the objective response rate? Can you contextualize the efficacy? And as you do that, maybe we'll think about what you'd expect in the context of, say, gastric cancer, especially in patients who've never really had a prior checkpoint inhibitor before. What do you think about the ORR? What do you think about the relative efficacy of this combination? Dr. Jason Luke: Well, so, in the study, they described overall response rate in the 36 patients as 36% and described immediate progression for survival of about 6.5 months. And so that was among patients who were treatment naive. And in second-line patients, they actually described an even higher response rate, although it was only 11 patients, but they're at 64%. And so, I think those data look to be somewhat interesting. When I was actually scrutinizing the actual data presented, it was of some interest to note that the quality of responses seemed to be about as good on the lower dose of LM-108, so 3 milligrams per kilogram as compared to 10 milligrams per kilogram. I think there's definitely more to learn here to try to optimize the dose and to fully understand what the overall efficacy of this treatment combination would be.  I would emphasize that in this disease, I think novel treatment strategies are certainly warranted. While anti PD-1 with chemotherapy has moved the needle in terms of standard of care treatment, it's really only a minor subset of patients who derive durable long-term benefit like we normally associate with immune checkpoint blockade. I think these are preliminary data. They're very intriguing.   You alluded to earlier that this population of patients was an Asian data set, and it is well known that the efficacy of chemotherapy and immunotherapy does appear to be somewhat enhanced in Asian populations, and that goes to distributions of metastasis and tumor microenvironment effects, etc. Very difficult to try to tease any of that out in this abstract, other than to look at these data and suggest that this is pretty interesting, both from a novel therapeutic approach, we talked about the Tregs consideration, but also straight up on the efficacy because I think if these data could hold up in a larger number of patients, and particularly in a western population of patients, I think it would be very intriguing. Dr. Diwakar Davar: Certainly, ASCO 2024 had a lot of interesting data, including data from targeted agents, the LAURA trial, ADCs. But just focusing on the immune therapy subset, we certainly saw a lot of great advances in patients who were treated with neoadjuvant as well as relapse refractory disease in the context of RP1 and then a couple of newer agents such as this petosemtamab as well as LM-108. And of course, we cannot forget to highlight the extended DMFS data from the pembro vaccine study from KEYNOTE-942.  Jason, as always, thank you for taking a little bit of time out of your extremely busy schedule to come and give us insights as to how these agents are impacting the landscape. We really value your input and so thank you very much.  Dr. Jason Luke: Thank you for the opportunity. Dr. Diwakar Davar: And thank you to our listeners for your time today. You will find the links to all the abstracts that we discussed in the transcript of this episode. And finally, if you value the insights that you hear on this podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. So, thank you.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Follow today's speakers:   Dr. Diwakar Davar   @diwakardavar   Dr. Jason Luke   @jasonlukemd      Follow ASCO on social media:    @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn      Disclosures:       Dr. Diwakar Davar:     Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences    Consulting or Advisory Role: Instil Bio, Vedanta Biosciences    Consulting or Advisory Role (Immediate family member): Shionogi    Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences    Research Funding (Inst.): Zucero Therapeutics    Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy       Dr. Jason Luke:    Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX    Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine    Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure    Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)    Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

Treg and Vicky discuss the mini 10k, weight gain during marathon training, and how to keep the sport of running accessible and affordable. TW: Treg and Vicky discuss eating disorders in this episode. We completely understand if this isn't for you!

In this riveting episode of The Social Guys, we sit down with "Philly," also known as Paul Fisher, to dive into his extraordinary journey post-high school. Philly opens up about his adventurous life in the Navy, recounting tales of jumping off ships, firing 50-caliber guns, and the challenges of cooking for thousands on a carrier ship.One of the most gripping stories includes the moment Seal Team Six brought Osama Bin Laden onto the same ship Philly was stationed on. The conversation also touches on Philly's and Treg's last encounter before Philly's big move to Arizona and what life has been like in the desert.The crew doesn't stop there; they dive into trending topics, including Diddy's raid and Justin Bieber's baby. Plus, they take a look at some of the hottest TikTok trends of the moment. Don't miss this episode filled with thrilling stories, laughter, and up-to-date trending news!Tune in for an episode that promises to be both exciting and enlightening, offering a unique glimpse into life on the high seas and beyond with Philly.

Treg and Vicky discuss down weeks and the upcoming mini 10k before diving into myths part 2. They then go over their wins for the week which includes hot dogs and therapy.

Treg and Vicky talk about their long weekends and then start busting some common myths in the running community.

Treg and Vicky discuss a range of topics including rescuing cats in Barbados, a stray dog seen while running, choosing the bear, and everything you need to know about how to prepare for summer running! If you're interested in helping the Ocean Acres Animal Sanctuary, check out their website and Instagram page: https://www.oceanacresanimalsanctuary.org/ @oceanacresanimals

In Episode 82 of The Social Guys, the tables are turned as Rylan Ward steps into the host's seat to interview the crew about the exciting future of their rapidly growing digital marketing company, RMG. Get an insider's look at their ambitious goals, plans for expansion, and Treg's personal aspirations for the company as it continues to rise as a major powerhouse in the industry. But that's just the beginning! The conversation shifts gears as they dive into the latest trending topics, including the unexpected connection between Beyoncé's new song and a beloved children's TV show. The crew also shares their thoughts on intriguing podcasts, comedic movies, and the latest buzz surrounding Lindsay Lohan. Things get a bit cheeky with a round of naughty "Would You Rather" questions, followed by a deep dive into the META crash and the ever-evolving world of TikTok. Stay tuned as they check out the latest viral TikToks, featuring Tyler Cassidy's epic comeback, a bone-chilling cannon mishap, the adorable Golden Girls toddler, and many more surprises! Don't miss this jam-packed episode filled with laughter, insights, and all the latest trends. Tune in to The Social Guys Episode 82 Part Deux with Rylan Ward for a wild ride through the world of digital marketing and pop culture!

Treg and Vicky discuss Vicky's recent 10k that she raced watchless (gasp!), Tregue's, hot dogs, and how Treg trained for a marathon on a plant-based diet.

References Acta Pharmacol Sin. 2019 Aug;40(8): 1076–1084 Nucleus. 2022; 13(1): 236–276.  Cancers (Basel). 2023 Nov; 15(21): 5177 Dylan, R. 1965 "Like a Rolling Stone" https://youtu.be/IwOfCgkyEj0?si=1vnIW2vqfsg-9MGp Dvorak, A. 1893. Symphony 9 in E minor. Op.95.B178. "From the New World" https://youtu.be/jOofzffyDSA?si=LiM8g7l487jmD22J --- 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

Treg and Vicky are back for another episode where they only talk about pigeons for a very short amount of time (womp womp) because they have much more interesting topics to cover!

Buckle up for this wildly entertaining episode of The Social Guys, where we're joined by the remarkably versatile Brad Heckathorn. Not only is Brad a mastermind behind organizing a girls' basketball league, but he's also teamed up with Treg to develop a summer Golf Camp for kids. This episode is packed with laughs as we delve into a spicy list of the top 50 sex fetishes and reminisce about comedic gems like "Tropic Thunder". We also dive into celebrity buzz around Jason Kelce and Taylor Swift, the frenzy of the Stanley Cup craze, and a hilarious story of an airplane passenger who just couldn't wait. Plus, we'll catch up on the latest and greatest in trending TikToks. Don't miss out on the fun—join us for a laugh-filled journey through sports, movies, and more on The Social Guys!

In this episode of AOA, Treg talks with Jonathan Beazley who has travelled as an evangelist, church planter, and fitness coach. Jonathan is going to share his struggles with church planting and ministry and how our fitness can advance our ministries as assistant pastors. Jonathan's website: mindandbodystrength.com  

durée : 00:27:13 - Le Feuilleton - Ayden, Liv et Od' font route vers l'Académie des druides. Lorsque leur maître, Tregòn, s'absente pour la nuit, ils décident de faire escale dans une étrange auberge perdue au milieu de la forêt. Mais ils ignorent encore que ce lieu cache un terrible secret…

Treg and Vicky are back and covering a variety of topics including their thoughts on banditing a race, Vicky's obsession with pigeons, something about PVC pipes (??) and how to get through a running injury.

The infamous Jersey City half/marathon race recap that we've been waiting for! Treg and Vicky spend the majority of the episode detailing how they both felt before/during/after the Jersey City race this past weekend, detailing Treg's incredible PR and BQ and in contrast, Vicky's panic attack at mile 3. This episode is truly for everyone! We hope you enjoy :)

This is part two of a conversation Treg and Dan began last episode. In this episode Treg and Dan talk more specifically about what a thrown spear looks like in ministry and talk about some helpful ways for assistant pastors to avoid those thrown spears.