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Send us a textWelcome to our Season 10 opening episode! Today we're discussing some of the big updates in metastatic breast cancer research from the 2024 San Antonio Breast Cancer Symposium (SABCS). Joining us today is Dr. Debu Tripathy, breast oncologist at The University of Texas MD Anderson Cancer Center who will break down into understandable terms some of the most impactful findings shared at SABCS, from advances in endocrine therapy and HER2-targeted treatments to exciting developments in PI3K inhibition and nausea control.
En este primer episodio de BreastLink, el Dr. Juan Carlos Samamé, oncólogo médico, Vicepresidente de LABCA en Lima, Perú, da la bienvenida a la Dra. Eva Ciruelos, una destacada especialista en cáncer de mama y Vicepresidenta del grupo SOLTI en Madrid, España. En esta dinámica, se centraron en el estudio PATINA, un ensayo fase III que explora el uso de palbociclib como tratamiento de mantenimiento en pacientes con cáncer de mama avanzado RH+/HER2-positivo. A lo largo del podcast, la Dra. Ciruelos detalla los objetivos del estudio, su población, y cómo este tratamiento busca mejorar la supervivencia libre de progresión (SLP), sin sustituir terapias existentes, sino complementándolas.Durante la conversación, la Dra. Ciruelos explica los resultados del estudio PATINA, destacando una mejora significativa en la SLP en el grupo que recibió palbociclib, con una mediana de 44.3 meses frente a los 29.1 meses del grupo de control. Además, se habló sobre antecedentes de otros estudios como monarcHER y PATRICIA, que también analizaron inhibidores de CDK4/6 en contextos similares. También se discutió la relevancia de estos tratamientos en el contexto de la enfermedad metastásica y cómo la combinación de terapias dirigidas al ciclo celular, bloqueo de HER2 y estrógeno, puede ser una opción importante para prolongar la respuesta sin recurrir a tratamientos más agresivos como la quimioterapia. Finalmente, se abordó el futuro de las terapias de mantenimiento y la necesidad de desescalar tratamientos a largo plazo en pacientes que han mostrado respuesta prolongada, así como la integración de nuevos inhibidores de PI3K.Dentro de su conversación, se plantearon las siguientes preguntas:¿Cómo el estudio PATINA busca mejorar la SLP en pacientes con cáncer de mama avanzado RH-positivo?¿Cuál fue el impacto de palbociclib en la SLP en comparación con el grupo control?¿Cómo se relacionan los resultados del estudio PATINA con otros estudios previos como monarcHER o PATRICIA?¿Cuál es el enfoque clínico actual en cuanto a la desescalada de tratamientos a largo plazo en pacientes con cáncer de mama avanzado?¿Qué nuevas terapias y combinaciones se perfilan a futuro, como los inhibidores de PI3K, y cómo podrían cambiar el manejo de estos pacientes?Fecha de grabación: 12 de febrero de 2025. Todos los comentarios emitidos por los participantes son a título personal y no reflejan la opinión de ScienceLink u otros. Se deberá revisar las indicaciones aprobadas en el país para cada uno de los tratamientos y medicamentos comentados. Las opiniones vertidas en este programa son responsabilidad de los participantes o entrevistados, ScienceLink las ha incluido con fines educativos. Este material está dirigido a profesionales de la salud exclusivamente.
In today's episode, supported by Genentech, we had the pleasure of speaking with Komal Jhaveri, MD, FACP, about the clinical use of inavolisib (Itovebi) for patients with hormone receptor (HR)–positive, PIK3CA-mutated, locally advanced or metastatic breast cancer. Dr Jhaveri is section head of the Endocrine Therapy Research Program, clinical director of the Early Drug Development Service, and the Patricia and James Cayne Chair for Junior Faculty at Memorial Sloan Kettering Cancer Center in New York, New York. In our exclusive interview, Dr Jhaveri discussed the importance of having a PI3K inhibitor available for the treatment of patients with HR-positive metastatic breast cancer, advice for managing inavolisib-related adverse effects, and best practices for early biomarker testing in patients with breast cancer.
Welcome to another episode of the Oncology Brothers podcast! In this episode, Drs. Rahul and Rohit Gosain are joined by Dr. Alok Khorana, a GI medical oncologist from the Cleveland Clinic, to discuss the latest highlights from the GI ASCO 2025 conference. We dive into four key studies that are practice-informing and potentially practice-changing: 1. BREAKWATER: We explore the implications of using Encorafenib and Cetuximab in combination with FOLFOX for patients with BRAF V600E mutations, which are associated with poor prognosis. 2. CheckMate-8HW: This study investigates whether dual checkpoint inhibition is more effective than single-agent immunotherapy for MSI-high patients, revealing promising results in progression-free survival. 3. Aspirin in Adjuvant Settings: We discuss the role of low-dose aspirin in reducing recurrence rates for patients with PI3K alterations, highlighting its potential as a practice-changing intervention. 4. STARTER-NET: Finally, we review the findings from the study on Everolimus combined with Lanreotide for neuroendocrine tumors, noting the lack of overall survival benefit. Tune in for an insightful discussion on these important topics in oncology, and learn how these findings could impact treatment strategies in your practice. Don't forget to like, subscribe, and check out our other episodes for more conference highlights and treatment discussions! YouTube: https://youtu.be/YOToz3hKYTg Follow us on social media: • X/Twitter: https://twitter.com/oncbrothers • Instagram: https://www.instagram.com/oncbrothers #OncologyBrothers #GIASCO2025 #ColorectalCancer #Immunotherapy #NeuroendocrineTumors #CancerResearch #Podcast
The J.P. Morgan Healthcare Conference kicked off Monday with a flood of high-value deals, reinvigorating sentiment across the biopharma industry. Johnson & Johnson made the biggest splash, acquiring neurology leader Intra-Cellular Therapies for $14.6 billion, while GSK picked up precision therapy specialist IDRx for $1B upfront and Eli Lilly laid down up to $2.5 billion for Scorpion's PI3Kα inhibitor program. Meanwhile, the immunology and inflammation space continues to fire on all cylinders as Gilead invests up to $1.7 billion for LEO Pharma's preclinical oral small molecule STAT6 program. And those are only the deals accepted by both parties. Prior to the conference, Biogen offered to acquire its struggling neuro partner Sage Therapeutics for around $469M. The proposal follows a catastrophic run for Sage, which has seen its shares fall more than 90% in the past two years. 2024 sales and earnings forecasts have also generated attention this week, with Sarepta reporting that Duchenne muscular dystrophy gene therapy Elevidys beat analysts' expectations in the fourth quarter, and Eli Lilly projecting a full-year revenue miss driven largely by lower-than-expected sales of GLP-1 blockbusters Zepbound and Mounjaro. As expected, obesity has been a hot topic at JPM, with Pfizer CEO Albert Bourla announcing that his company is going “all in” in the space. This follows new FDA guidance revealed last week recommending a minimum weight loss threshold for drug developers. Among the many companies taking notice is newcomer Verdiva Bio, which launched last week with more than $410 million in opening funds. Also debuting last week was Kardigan, which raised $300 million to tackle heart disease. Kadigan joins a resurgent cardiovascular space, where several companies—including those developing gene therapies—are targeting myriad diseases. Finally, BioSpace senior editor Annalee Armstrong caught up with Daphne Zohar, CEO of BioSpace NextGen 2025 company Seaport Therapeutics Daphne Zohar, who offered her thoughts on the current state of the neuropsychiatric space.
Featuring articles on semaglutide in persons with obesity and knee osteoarthritis, the addition of PI3K inhibition in breast cancer, treatments in older patients with myeloma, and total hip replacement for hip osteoarthritis; a review article on lead poisoning; a case report of a man with dyspnea after old myocardial infarction; and Perspectives on large language models and the medical record, on measuring AI against the health care we have, on the failing U.S. health system, and on the contemporary rise of pronatalism.
BUFFALO, NY- October 30, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on October 11, 2024, entitled “Initiation of tumor dormancy by the lymphovascular embolus.” Researchers Yin Ye, Justin Wang, Michael G. Izban, Billy R. Ballard, and Sanford H. Barsky from Meharry Medical College in Nashville, TN, and Scripps Mercy Hospital in San Diego, CA, uncovered critical mechanisms that lead to tumor dormancy in breast cancer. This study sheds light on how certain cancer cells can remain dormant for years before potentially reawakening as metastatic tumors. Using breast cancer patient-derived organoids and tumor samples, the research team discovered that tumor dormancy in breast cancer can be triggered by specific signaling changes within small cell clusters, called tumor emboli, which detach from the primary tumor and travel through the bloodstream. These emboli can remain inactive, sometimes for years, before reawakening in other parts of the body. Key changes include reduced activity of mTOR, a metabolic regulator, and structural shifts in E-cadherin, a molecule involved in cell adhesion. This study also suggests these changes are regulated by the PI3K pathway and occur within the unique three-dimensional structure of tumor spheroids, shedding light on the interactions within dormant cell clusters. As a conclusion, this work not only identifies mTOR and E-cadherin as key components in maintaining dormancy but also offers a promising roadmap for future therapies. By targeting these pathways, there may be potential to keep cancer cells in a dormant state, reducing the risk of late-stage recurrence and improving patient outcomes. DOI - https://doi.org/10.18632/oncotarget.28658 Correspondence to - Sanford H. Barsky - sbarsky@mmc.edu Video short - https://www.youtube.com/watch?v=z6ex7Yl8r5Q Sign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28658 Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/ Keywords - cancer, dormancy, lymphovascular embolus, mTOR, E-cadherin proteolysis About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM
In this episode, Ayesha spoke with Sam Lee, PhD, Co-Chief Executive Officer and President of Cocrystal Pharma, a company developing novel antiviral therapeutics against COVID-19 and other coronaviruses, influenza viruses and noroviruses.Cocrystal Pharma leverages a unique structure-based drug discovery platform, complemented by Nobel Prize-winning expertise, to develop leading-edge antiviral drugs that are both first-in-class and best-in-class. Their antivirals specifically target the viral replication process and are designed for safety, broad-spectrum effectiveness, resistance management and ease of administration.Dr. Lee brings over 25 years of experience in anti-infective drug discovery research to his role. Before joining Cocrystal, he spent eight years overseeing anti-infective drug discovery initiatives at Icos Corporation. During his tenure at Icos, Dr. Lee integrated protein crystallography and structural screening technologies into the company's research programs and was instrumental in the development of phosphoinositide 3-kinase (PI3K) delta inhibitors, leading to an FDA-approved product. Dr. Lee earned his PhD in Biological Sciences from the University of Notre Dame and completed his postdoctoral training in viral biochemistry at Stanford University. While at Stanford, he also established Viral Assays in Cupertino, CA, where he served as CEO.Tune in to the episode to learn about Cocrystal Pharma's structure-based drug discovery approach to developing next-gen antiviral treatments. For more life science and medical device content, visit the Xtalks Vitals homepage. https://xtalks.com/vitals/ Follow Us on Social MediaTwitter: 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
Unlock the hidden truths about sugar's role in cancer as we sit down with chemist Dr. Lewis Cantley, whose work on the PI3K enzyme has revolutionized our understanding of this sweet substance's dark side. Picture a world where sugar isn't just a harmless treat but a trigger for one of today's leading health adversaries. This episode takes you on a journey through Dr. Cantley's personal dietary choices, stemming from his own health experiences, to his groundbreaking research that connects the dots between sugar intake, insulin spikes, and cancer cell proliferation. It's a narrative that not only sheds light on the molecular mechanisms of the Warburg effect but also opens the door to potential dietary interventions in chronic disease management.As we navigate the complexities of insulin resistance and its implications for both diabetes and cancer, we discover the pivotal discoveries in Dr. Cantley's lab. Here, the connection between high insulin levels and cancer risk emerges with startling clarity, as does the life-changing impact of insulin's discovery on diabetes treatment. This episode doesn't just leave you with alarming insights; it arms you with the knowledge needed to challenge dietary norms and embrace a path to longevity through informed nutrition. Join us as we dissect the profound impact of lifestyle choices on cancer risks, and learn how a simple decision at the dinner table could drastically alter your health's trajectory.Florence's courses & coaching programs can be found at:www.FlorenceChristophers.comConnect with Florence on:FACEBOOK | TWITTER | INSTAGRAM | YOUTUBE
In this podcast, our faculty discuss some newer treatment approaches for patients with HR-positive breast cancer including PI3K inhibition, AKT inhibition, and oral selective estrogen receptor down regulators. Visit www.morningcommutepodcast.com/HRPositiveBreast1 to view the activity and CME/CE information, download the transcript, and complete the post-test and evaluation to earn CME/CE credit.
Description: Dr. Maya Graham interviews Dr. Evan Noch about his and his team's recent manuscript entitled: "Insulin feedback is a targetable resistance mechanism of PI3K inhibition in glioblastoma", published online in Neuro-Oncology in July 2023. Read Paper
Click here to view and claim credit for Managing Toxicities of Novel Breast Cancer Therapies: PI3K Inhibitors, an accredited CME/NCPD/CPE activity by i3 Health: i3health.com/odabc-pi3k. Phosphatidylinositol-3-kinase (PI3K) inhibitors are effective treatment for patients with breast cancer but can be associated with significant hyperglycemia and rash. In this interview from the 48th Annual Oncology Nursing Society (ONS) Congress, Janie Metsker, RN, BSN, CN-BN, Clinical Coordinator at St. Luke's Koontz Center for Advanced Breast Cancer, shares updated strategies for managing these toxicities in order to provide the best outcomes for patients with breast cancer receiving PI3K inhibitors.
A new research paper was published in Aging (Aging-US) Volume 15, Issue 7, entitled, “Characterization of the HDAC/PI3K inhibitor CUDC-907 as a novel senolytic.” The accumulation of senescent cells has an important role in the phenotypical changes observed in aging and in many age-related pathologies. Thus, the strategies designed to prevent these effects, collectively known as senotherapies, have a strong clinical potential. Senolytics are a type of senotherapy aimed at specifically eliminating senescent cells from tissues. Several small molecule compounds with senolytic properties have already been identified, but their specificity and range of action are variable. Because of this, potential novel senolytics are being actively investigated. Given the involvement of HDACs and the PI3K pathway in senescence, researchers Fares Al-Mansour, Abdullah Alraddadi, Buwei He, Anes Saleh, Marta Poblocka, Wael Alzahrani, Shaun Cowley, and Salvador Macip from the University of Leicester, Najran University and Universitat Oberta de Catalunya hypothesized that the dual inhibitor CUDC-907, a drug already in clinical trials for its antineoplastic effects, could have senolytic effects. “Here, we show that CUDC-907 was indeed able to selectively induce apoptosis in cells driven to senesce by p53 expression, but not when senescence happened in the absence of p53.” Consistent with this, CUDC-907 showed senolytic properties in different models of stress-induced senescence. Their results also indicate that the senolytic functions of CUDC-907 depend on the inhibitory effects of both HDACs and PI3K, which leads to an increase in p53 and a reduction in BH3 pro-survival proteins. Taken together, their results show that CUDC-907 has the potential to be a clinically relevant senolytic in pathological conditions in which stress-induced senescence is involved. “According to our results, CUDC-907 could be an interesting drug to be used as a senolytic, alone or as part of a targeted approach.” DOI: https://doi.org/10.18632/aging.204616 Corresponding author - Salvador Macip - sm460@le.ac.uk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204616 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence, senolytics, HDAC, PI3K, CUDC-907 About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM
This month on Episode 46 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the March 3 and March 17th issues of Circulation Research. This episode also features an interview with Dr Andrew Hughes and Dr Jessilyn Dunn about their review, Wearable Devices in Cardiovascular Medicine. Article highlights: Delgobo, et al. Deep Phenotyping Heart-Specific Tregs Sun, et al. Inhibition of Fap Promotes Cardiac Repair After MI Sun, et al. Endosomal PI3Kγ Regulates Hypoxia Sensing Johnson, et al. Hypoxemia Induces Minimal Cardiomyocyte Division Cindy St. Hilaire: Hi, and welcome to Discover CircRes, the podcast of the American Heart Association's Journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire from the Vascular Medicine Institute at the University of Pittsburgh, and today I'm going to share four articles selected from the March 3rd and March 17th issues of CircRes. I'm also going to have a discussion with Dr Andrew Hughes and Dr Jessilyn Dunn about their review, Wearable Devices in Cardiovascular Medicine. And the Review is also featured in our March 3rd issue. Cindy St. Hilaire: First, the highlights. The first article I'm going to present is Myocardial Milieu Favors Local Differentiation of Regulatory T-Cells. The first author is Murilo Delgobo and the corresponding author is Gustavo Campos Ramos. After myocardial infarction, the release of autoantigens from the damaged heart cells activates local and infiltrating immune cells such as the T-cell. Studies in mice have shown that fragments of the muscle protein myosin can act as autoantigens, and these myosin fragments are the dominant driver of the T-cell response. But how do these myosin specific T-cells behave in the damaged heart to drive inflammation and repair is unknown. To find out, Delgobo and colleagues studied endogenous myosin specific T-cells, as well as those transferred into recipient mice. They found, whether exogenously supplied or endogenously created, the myosin specific T-cells that accumulated in the animals' infarcted hearts tended to adopt an immunosuppressive T-regulatory phenotype. Strikingly, even if the exogenous cells were differentiated into inflammatory TH-17 cells prior to transfer, a significant proportion of them were still reprogrammed into T-regs within the heart. Although cells pre-differentiated into an inflammatory TH-17 phenotype were less inclined to change after the transfer, the results nevertheless indicate that, by and large, the infarcted heart promotes T-cell reprogramming to quell inflammation and drive repair. Yet exactly how the heart does this is a question for future studies. Cindy St. Hilaire: The next article I'm going to present is titled Inhibition of FAP Promotes Cardiac Repair by Stabilizing BNP. The first authors of the study are Yuxi Sun and Mengqiu Ma, and the corresponding author is Rui Yue, and they are from Tongji University. After myocardial infarction, there needs to be a balance of recovery processes to protect the tissue. Fibrosis, for example, acts like an immediate bandaid to hold the damaged heart muscle together, but fibrosis can limit contractile function. Similarly, angiogenesis and sufficient revascularization is required to promote survival of cardiomyocytes within the ischemic tissue and protect heart function. To better understand the balance between fibrotic and angiogenic responses, Sun and colleagues examined the role of fibroblasts activated protein, or FAP, which is dramatically upregulated in damaged hearts, and brain natriuretic peptide, or BNP, which promotes angiogenesis in the heart. In this study, they found that genetic deletion or pharmacological inhibition of FAP in mice reduces cardiac fibrosis and improves angiogenesis and heart function after MI. Such benefits are not seen if BNP or its receptor, NRP-1, are lacking. The in vitro experiments revealed that FAP's protease activity degrades BNP, thus inhibiting the latter's angiogenic activity. Interestingly, while FAP is upregulated in the heart, its levels drop in the blood, showing that BNP inhibition is localized. Together, these results suggest that blocking FAP's activity in the heart after MI could be a possible strategy for protecting the muscle's function. Cindy St. Hilaire: The next article I want to present is Hypoxia Sensing of Beta-Adrenergic Receptor is Regulated by Endosomal PI-3 Kinase Gamma. The first author of this study is Yu Sun, and the corresponding author is Sathyamangla Naga Prasad. Hypoxia is the most proximate acute stress encountered by the heart during an ischemic event. Hypoxia triggers dysfunction of the beta-adrenergic receptors, beta-1AR and beta-2AR, which are critical regulators of cardiac function. Under normoxic conditions, activation of PI3K-gamma by beta-adrenergic receptors leads to feedback regulation of the receptor by hindering its dephosphorylation through inhibition of protein phosphatase 2A or PP2A. Although it is known that ischemia reduces beta-adrenergic receptor function, the impact of hypoxia on interfering with this PI3K feedback loop was unknown. Using in vitro and in vivo techniques, this group found that activation of PI3K-gamma underlies hypoxia sensing mechanisms in the heart. Exposing PI3K-gamma knockout mice to acute hypoxia resulted in preserved cardiac function and reduced beta-adrenergic receptor phosphorylation. And this was due to a normalized beta-2AR associated PP2A activity, thus uncovering a unique role for PI3K-gamma in hypoxia sensing and cardiac function. Similarly, challenging wild-type mice post hypoxia with dobutamine resulted in an impaired cardiac response that was normalized in the PI3K-gamma knockout mice. These data suggests that preserving beta-adrenergic resensitization by targeting the PI3K-gamma pathway would maintain beta-adrenergic signaling and cardiac function, thereby permitting the heart to meet the metabolic demands of the body following ischemia. Cindy St. Hilaire: The last article I want to highlight is Systemic Hypoxia Induces Cardiomyocyte Hypertrophy and Right Ventricle Specific Induction of Proliferation. First author of this study is Jaslyn Johnson, and the corresponding author is Steven Houser, and they're at Temple University. The cardiac hypoxia created by myocardial infarction leads to the death of the heart tissue, including the cardiomyocytes. While some procedures such as reperfusion therapy prevent some cardiomyocyte death, true repair of the infarcted heart requires that dead cells be replaced. There have been many studies that have attempted new approaches to repopulate the heart with new myocytes. However, these approaches have had only marginal success. A recent study suggested that systemic hypoxemia in adult male mice could induce cardiac monocytes to proliferate. Building on this observation, Johnson and colleagues wanted to identify the mechanisms that induced adult cardiomyocyte cell cycle reentry and wanted to determine whether this hypoxemia could also induce cardiomyocyte proliferation in female mice. Mice were kept in hypoxic conditions for two weeks, and using methods to trace cell proliferation in-vivo, the group found that hypoxia induced cardiac hypertrophy in both the left ventricle and the right ventricle in the myocytes of the left ventricle and of the right ventricle. However, the left ventricle monocytes lengthened while the RV monocytes widened and lengthened. Hypoxia induced an increase in the number of right ventricular cardiomyocytes, but did not affect left ventricular monocyte proliferation in male or in female mice. RNA sequencing showed upregulation of cell cycle genes which promote the G1 to S phase transition in hypoxic mice, as well as a downregulation of cullen genes, which are the scaffold proteins related to the ubiquitin ligase complexes. There was significant proliferation of non monocytes in mild cardiac fibrosis in the hypoxic mice that did not disrupt cardiac function. Male and female mice exhibited similar gene expression patterns following hypoxia. Thus, systemic hypoxia induced a global hypertrophic stress response that was associated with increased RV proliferation, while LV monocytes did not show increased proliferation. These results confirm previous reports that hypoxia can induce cardiomyocyte cell cycle activity in-vivo, and also show that this hypoxia induced proliferation also occurs in the female mice. Cindy St. Hilaire: With me today for our interview, I have Dr Andrew Hughes and Dr Jessilyn Dunn, and they're from Vanderbilt University Medical Center. And they're here to discuss the review article that they helped co-author called Wearable Devices in Cardiovascular Medicine. And just as a side note, the corresponding author, Evan Brittain, unfortunately just wasn't able to join us due to clinical service, but they're going to help dissect and discuss this Review with us. Thank you both so much for joining me today. Andy, can you just tell us a little bit about yourself? Andy Hughes: Yeah, thank you, Cindy. I'm Andy Hughes. I'm a third year medicine resident at Vanderbilt University who is currently on an NIH supported research year this year. And then will be applying to cardiology fellowships coming up in the upcoming cycle. Cindy St. Hilaire: Great, thank you. And Jessilyn, I said you are from Vanderbilt. I know you're from Duke. It was Evan and Andy at Vanderbilt. Jessilyn, tell us about yourself. Jessilyn Dunn: Thanks. I am an Assistant Professor at Duke. I have a joint appointment between biomedical engineering and biostatistics and bioinformatics. The work that my lab does is mainly centered on digital health technologies in developing what we call digital biomarkers, using data from often consumer wearables to try to detect early signs of health abnormalities and ultimately try to develop interventions. Cindy St. Hilaire: Thank you. We're talking about wearable devices today, and obviously the first thing I think most of us think about are the watch-like ones, the ones you wear on your wrists. But there's really a whole lot more out there. It's not just Apple Watches and Fitbits and the like. Can you just give us a quick summary of all these different types of devices and how they're classified? Jessilyn Dunn: Yeah, absolutely. We have a wide variety of different sensors that can be useful. A lot of times, we like to think about them in terms of the types of properties that they measure. So mechanical properties like movement, electrical properties like electrical activity of the heart. We have optical sensors. And so, a lot of the common consumer wearables that we think about contain these different types of sensors. A good example that we can think about is your consumer smartwatch, like an Apple Watch or a Fitbit or a Garmin device where it has something called an accelerometer that can measure movement. And oftentimes, that gets converted into step counts. And then it may also have an optical sensor that can be used to measure heart rate in a particular method called PPG, or photoplethysmography. And then some of the newer devices also have the ability to take an ECG, so you can actually measure electrical activity as well as the optical based PPG heart rate measurement. These are some of the simpler components that make up the more complex devices that we call wearables. Cindy St. Hilaire: And how accurate are the measurements? You did mention three of the companies, and I know there's probably even more, and there's also the clinical grade at-home ECG machines versus the one in the smartwatch. How accurate are the measurements between companies? And we also hear recent stories about somebody's Apple Watch calling 911 because they think they're dead, things like that. Obviously, there's proprietary information involved, but how accurate are these devices and how accurate are they between each other? Jessilyn Dunn: This is a really interesting question and we've done quite a bit of work in my lab on this very topic, all the way from what does it mean for something to be accurate? Because we might say, "Well, the more accurate, the better," but then we can start to think about, "Well, how accurate do we need something to be in order to make a clinical decision based off of that?" And if it costs significantly more to make a device super, super accurate, but we don't need it to be that accurate to make useful decisions, then it actually might not be serving people well to try to get it to that extreme level of accuracy. So there are a lot of trade-offs, and I think that's a tough thing to think about in the circumstances, is these trade-offs between the accuracy and, I don't know, the generalizability or being able to apply this to a lot of people. That being said, it also depends on the circumstances of use. When we think about something like step counts, for example, if you're off by a hundred step counts and you're just trying to get a general view of your step counts, it's not that much of a problem. But if we're talking about trying to detect an irregular heart rhythm, it can be very bad to either miss something that's abnormal or to call something abnormal that's not and have people worried. We've been working with the Digital Medicine Society to develop this framework that we call V3, which is verification, analytic validation and clinical validation. And these are the different levels of analysis or evaluation that you can do on these devices to determine how fit for purpose are they. Given the population we're trying to measure in and given what the goal of the measurement is, does the device do the job? And what's also interesting about this topic is that the FDA has been evolving how they think about these types of devices because there's, in the past, been this very clear distinction between wellness devices and medical devices. But the problem is that a lot of these devices blur that line. And so, I think we're going to see more changes in the way that the FDA is overseeing and potentially regulating things like this as well. Cindy St. Hilaire: These consumer-based devices have started early on as the step counters. When did they start to bridge into the medical sphere? When did that start to peak the interest of clinicians and researchers? Jessilyn Dunn: Yeah, sure. What's interesting is if we think back to accelerometers, these have been used prior to the existence of mobile phones. These really are mechanical sensors that could be used to count steps. And when we think about the smartwatch in the form that we most commonly think of today, probably looking back to about 2014 is when ... maybe between 2012, 2014 is when we saw these devices really hitting the market more ... Timing for when the devices that we know as our typical consumer smartwatch today was around 2012 to 2014. And those were things that were counting steps and then the next generation of that added in the PPG or photoplethysmography sensor. That's that green light when we look on the back of our watch that measures heart rate. And so, thinking back to the early days, probably Jawbone, there was a watch called Basis, the Intel Basis watch. Well, it was Basis and then got acquired by Intel. Fitbit was also an early joining the market, but that was really the timing. Cindy St. Hilaire: How good are these devices at actually changing behavior? We know we're really good at tracking our steps now and maybe monitoring our heartbeat or our oxygen levels. How good are they at changing behavior though? Do we know yet? Andy Hughes: Yeah, that's a great question and certainly a significant area of ongoing research right now with physical activity interventions. Things that we've seen right now is that simple interventions that use the wearable devices alone may not be as effective as multifaceted interventions. And what I mean by that is interventions that use the smartwatch but may be coupled with another component, whether that is health education or counseling or more complex interventions that use gamification or just in time adaptive interventions. And gamification really takes things to another level because that integrates components, competition or support or collaboration and really helps to build upon features of behaviors that we know have an increased likelihood of sustaining activity. With that being said, that is one of the challenges of physical activity interventions, is the sustainability of their improvements over the course of months to years. And something that we have seen is the effects do typically decrease over time, but there is work on how do we integrate all of these features to develop interventions that can help to sustain the results more effectively. So we have seen some improvement, but finding ways to sustain the effects of physical activity is certainly an area of ongoing research. Cindy St. Hilaire: I know it's funny that even as adults we love getting those gold stars or the circle completions. All of these devices, whether it's smartwatches like we're just talking about, or the other things for cardiac rehabilitation, they're generating a ton of data. What is happening with all this data? Who's actually analyzing it? How is it stored and what's that flow through from getting from the patient's body to the room where their physician is looking at it? Andy Hughes: And that is certainly a challenge right now that is limiting the widespread adoption of these devices into routine clinical care is, as Jessilyn mentioned. The wearables generate a vast amount of data, and right now, we need to identify and develop a way as clinicians to sort through all of the noise in order to be able to identify the information that is clinically meaningful and worthy of action without significantly increasing the workload. And a few of the barriers that will be necessary in order to reach that point is, one, finding ways to integrate the wearables' data into the electronic health record and also developing some machine learning algorithms or ways with which we can use the computational power of those technologies to be able to identify when there is meaningful data within all of the vast data that comes from wearables. So it's somewhere that certainly we need to get to for these devices to reach their full clinical potential, but we are limited right now by a few of those challenges. Jessilyn Dunn: I was just going to say, I will add on to what Andy was saying about this idea behind digital biomarkers because this fits really nicely with this idea that giving people this huge data deluge is not helpful, but if we had a single metric where we can say, "Here's the digital biomarker of step count, and if you're above some threshold, you're good to go. And if you're below some threshold, some intervention is needed." That's a lot of the work that we've been doing, is trying to develop what are these digital biomarkers and how can they be ingested in a really digestible way? Cindy St. Hilaire: Yeah, that's great. Regarding the clinical and the research grade devices, I know a Fitbit or Apple Watch can sometimes be used for those, but I guess I'm talking also about the other kind of more clinically oriented devices, how good is compliance and how trustable is that data? Everybody's on probably their best behavior when they're in the office with the physician or if they're on the treadmill in the cardiac lab, but home is a different story. And what don't we know about compliance when people are out of the office and the reliability of that data that's generated in that space? Andy Hughes: I think you touched on a really important point right here, and one of the potential advantages of these wearable devices is that they provide continuous long-term monitoring over the course of weeks to months to years as opposed to those erratic measurements that we get from the traditional office visits or hospitalizations where, for example, the measurements we're taking are either in a supervised environment with a six-minute walk distance, for example, or self-reported or questionnaires. So we build upon that information, but then additionally, we go beyond the observer effect where many individuals, the first week or two that you're wearing this new device, you may be more prone to increase your activity because you know that you're being monitored or you have this novel technology, but as you wear it for months to years, you outgrow those potential biases and you really can garner more comprehensive information. In terms of compliance, we can speak to some of the research studies that have either really struggled with compliance and that limits the interpretability of their results and something we'll need to address in the future, but I think that's something that can be addressed with future studies keeping in mind all of the advantages that these devices offer compared to some of the traditional measures that we have used in the past. Cindy St. Hilaire: With all this data we're collecting, whether it be biological data or even just behavioral data, have we actually learned anything new? And I mean that in terms of All Of Us study this, I don't know, it was like 5,000 patients I think, and lo and behold, it found out that higher step count correlated with lower risk for a ton of diseases, which is not exactly groundbreaking. So are we, at this point in time, learning anything new from the use of these at-home devices, or are they really just able to help us enforce what we thought we knew regarding behavior? Andy Hughes: I think these devices have certainly provided some novel insights that build upon our understanding of physical activity. Many of us can hypothesize that decreased activity would have poor outcomes on health, which the studies have demonstrated in many facets. But in reference to All Of Us study that you mentioned, I think it's interesting to look as well at some of the diagnoses or conditions that were associated with decreased activity. For example, reflux disease was also highlighted in that study, which may not have been identified if we didn't have the vast data and ability to really look for associations with diseases that have not been previously studied or thought to be related to physical activity. So I think that's one of the strong features of that database, is the wealth of knowledge that really will be hypothesis generating and help to inform future studies as we look even beyond cardiovascular conditions. Cindy St. Hilaire: One question, and you did bring it up in a bit of the discussion in your piece, is the bias that is in these devices. We know from COVID at-home pulse oximeters do not work as efficiently on darker skin. We actually know that going into bathrooms with the hand sensors that spit out the paper towels. So what kind of disparities or biases do these devices create or reinforce in the population? Jessilyn Dunn: This is such a critical topic because a lot of these issues had been discovered retrospectively because the people who were developing the technologies were not the representative of the people who were using the technologies. I think that's something that across the board we've been looking at from device development to AI implementation, which is having people who are going to be using the devices in the process of developing the technology and having voices heard from across the board. We did a detailed look when we were evaluating devices for their accuracy at this exact question of where the heart rate sensors in smartwatches use optical based technology. And there was some evidence that was also an issue for people with varying skin tones, for people with wrist tattoos or more hair or freckles. And so, we did a deep dive and the generation of devices that we looked at which would meet this study was probably about three years ago. We didn't see any discrepancies. And so, that's just one study and there are many more to be done, but I think prior to the technology development as well as once the technology comes out, keeping an eye on how that technology is doing, whether there are continued reports of failure of the technologies is really important. And there are a lot of ways that we can be vigilant about that. Cindy St. Hilaire: Yeah, that's great. And so, Andy, regarding patient populations, I can also see perhaps socioeconomic implications of this because smartwatches are not cheap. So how do we see that in terms of helping our patients? Are we going to be able to get a smartwatch through our insurance company? Andy Hughes: I think that's one of the really important next steps, is finding ways to make sure that as we advance the field of wearable devices in clinical care, that we recognize some of the existing inequities in terms of access to care, access to digital technologies that currently exist, and find ways by partnering with health insurance companies and the industry and providers and members of that community, finding ways to not only advance wearables, but use it in a way that we can decrease health disparities by really helping to increase access for these digital technologies to the underserved communities. Jessilyn Dunn: Yeah, the beauty of these technologies is that truthfully, at their core, they're very cheap. They're not difficult to develop, they're not difficult to build and disseminate. So a lot of what we think about is the infrastructure that goes around these devices. Does it require a smartphone to transfer data? Does it require internet access? What are the other pieces that need to be in place for these devices to work within an ecosystem? So this starts to get to questions beyond the devices themselves, but there's certainly a lot to think about and be done in the area of equity and ensuring that these devices can help everyone. Cindy St. Hilaire: And there's also the, I guess, ethical considerations of who owns this data. Obviously, if it's a consumable that you went and bought at Target, that's probably different than the one you're getting from your cardiologist. But who owns the data? Who has access to it? And are there any cases in the literature where an individual who's had certain measurements taken, have those measurements come back to bite them? And I guess I'm thinking of something like cardiac rehab. If a patient doesn't get up and move enough or doesn't follow their physical therapy enough or lose weight quick enough, could their insurance coverage get cut? Could their premiums go up? What safeguards are in place for these very tricky situations? Are there safeguards in place? Andy Hughes: And on the clinical side, I think it will be important to treat this information just like any other protected health information that we have as part of the electronic health record. And so, there will be inherently safeguards around that in a similar manner for how we treat other protected health information. But I think another important component of that will be a very clear consent policy when we reach the point that patients are consenting to include this information and their electronic health record, in terms of what the proposed benefits are and the potential risks associated with it, because it really is a vast amount of unique data that needs to be protected and safeguarded. And part of that comes by treating it as protected health information, but we will also need to make sure that there's a very clear consent policy that goes with it. Cindy St. Hilaire: Yeah. What do we see as the next steps in wearable devices? What do you guys see as the next big thing? I know one's coming from the actual AI and device side of things, and the other one is coming from the clinical side of things. What do each of you see as the next thing in this field? Jessilyn Dunn: I think on the device and AI side of things, I think we're thinking toward improving battery life, increasing the suite of sensors that are being added to these devices so we have a wider variety of measurements that are more representative of physiology, and then better algorithms to have better detection of sleep or activity or certain types of activity or certain types of arrhythmias. This combination of hardware and software and algorithms, I think coming together as all of these different pieces evolve will show us some really cool technology in the years to come. Andy Hughes: And I think from a clinical side, it's really twofold moving forward. I think as Jessilyn mentioned, there's a lot of novel sensor technologies that have a lot of exciting and evolving potential that we can hopefully integrate into the clinical space, but on the other hand, it's how can we use these wearable devices to enhance traditional therapies that we're already using? For example, if we take the heart failure population, is there a way that we can use the wearable devices and the existing measurements with heart rate and physical activity and blood pressure to find a way to improve remote management and safely up-titrate guideline directed medical therapy, which are medications that we know have clinical benefit. But can we augment their clinical benefit and their utility by using some of the existing technologies that we already have? And then lastly, building upon the initial studies with larger trials in more diverse generalizable populations to really enhance our understanding of the benefits that these devices may have for different cardiovascular conditions. Cindy St. Hilaire: Well, this was wonderful. Dr Andrew Hughes and Dr Jessilyn Dunn, thank you so much for joining me. The review, Wearable Devices in Cardiovascular Medicine, will be out in our March 3rd issue of Circulation Research. I forget which one, so I'll have to edit that out. Thank you so much for joining us, and I learned a ton. This was great. Jessilyn Dunn: Thank you. Andy Hughes: Thank you. Cindy St. Hilaire: That's it for our highlights from the March 3rd and March 17th issues of Circulation Research. Thank you for listening. Please check out the Circulation Research Facebook page and follow us on Twitter and Instagram with the handle @CircRes and #DiscoverCircRes. Thank you to our guests, Dr Andrew Hughes and Dr Jessilyn Dunn. This podcast is produced by Ishara Ratnayaka, edited by Melissa Stoner, and supported by the editorial team of Circulation Research. Some of the copy texts for the highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire, and this is Discover CircRes, you're on-the-go Source for the most exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association, 2023. The opinions expressed by speakers in this podcast are their own, and not necessarily those of the editors or of the American Heart Association. For more information, visit ahajournals.org.
In this week's episode, we'll discuss the findings from a phase 3 trial of PI3Kδ inhibitor leniolisib in activated PI3Kd syndrome, learn more about the efficacy and safety of dabrafenib plus trametinib in relapsed/refractory BRAF V600E mutation-positive hairy cell leukemia, and review the findings from a study conducted in an international cohort of patients with Tγδ LGL leukemia.
Go online to PeerView.com/SZT860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Are you up to date on the latest evidence with immunotherapy, targeted agents, and chemo-free options for follicular lymphoma (FL)? Find out by accessing this activity, where an expert will interpret new evidence supporting the continued integration of bispecific antibodies, CAR-T cell therapy, EZH2 inhibitors, and PI3K inhibitors across multiple lines of therapy in relapsed/refractory FL. Throughout, the expert shares guidance on therapeutic sequencing, safety management, and the future use of innovative combination platforms. Don't miss this important update from ASH! Upon completion of this activity, participants should be better able to: Summarize evidence surrounding targeted, epigenetic, and immunotherapy options for R/R FL; Integrate modern, evidence-based sequential treatment plans for R/R FL that include immunomodulatory drugs, targeted therapies, epigenetic agents, bispecific antibodies, and CAR-T constructs; and Manage the unique suite of adverse events associated with the use of novel therapeutics as sequential management options in R/R FL
Go online to PeerView.com/SZT860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Are you up to date on the latest evidence with immunotherapy, targeted agents, and chemo-free options for follicular lymphoma (FL)? Find out by accessing this activity, where an expert will interpret new evidence supporting the continued integration of bispecific antibodies, CAR-T cell therapy, EZH2 inhibitors, and PI3K inhibitors across multiple lines of therapy in relapsed/refractory FL. Throughout, the expert shares guidance on therapeutic sequencing, safety management, and the future use of innovative combination platforms. Don't miss this important update from ASH! Upon completion of this activity, participants should be better able to: Summarize evidence surrounding targeted, epigenetic, and immunotherapy options for R/R FL; Integrate modern, evidence-based sequential treatment plans for R/R FL that include immunomodulatory drugs, targeted therapies, epigenetic agents, bispecific antibodies, and CAR-T constructs; and Manage the unique suite of adverse events associated with the use of novel therapeutics as sequential management options in R/R FL
Go online to PeerView.com/SZT860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Are you up to date on the latest evidence with immunotherapy, targeted agents, and chemo-free options for follicular lymphoma (FL)? Find out by accessing this activity, where an expert will interpret new evidence supporting the continued integration of bispecific antibodies, CAR-T cell therapy, EZH2 inhibitors, and PI3K inhibitors across multiple lines of therapy in relapsed/refractory FL. Throughout, the expert shares guidance on therapeutic sequencing, safety management, and the future use of innovative combination platforms. Don't miss this important update from ASH! Upon completion of this activity, participants should be better able to: Summarize evidence surrounding targeted, epigenetic, and immunotherapy options for R/R FL; Integrate modern, evidence-based sequential treatment plans for R/R FL that include immunomodulatory drugs, targeted therapies, epigenetic agents, bispecific antibodies, and CAR-T constructs; and Manage the unique suite of adverse events associated with the use of novel therapeutics as sequential management options in R/R FL
Go online to PeerView.com/SZT860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Are you up to date on the latest evidence with immunotherapy, targeted agents, and chemo-free options for follicular lymphoma (FL)? Find out by accessing this activity, where an expert will interpret new evidence supporting the continued integration of bispecific antibodies, CAR-T cell therapy, EZH2 inhibitors, and PI3K inhibitors across multiple lines of therapy in relapsed/refractory FL. Throughout, the expert shares guidance on therapeutic sequencing, safety management, and the future use of innovative combination platforms. Don't miss this important update from ASH! Upon completion of this activity, participants should be better able to: Summarize evidence surrounding targeted, epigenetic, and immunotherapy options for R/R FL; Integrate modern, evidence-based sequential treatment plans for R/R FL that include immunomodulatory drugs, targeted therapies, epigenetic agents, bispecific antibodies, and CAR-T constructs; and Manage the unique suite of adverse events associated with the use of novel therapeutics as sequential management options in R/R FL
Go online to PeerView.com/SZT860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Are you up to date on the latest evidence with immunotherapy, targeted agents, and chemo-free options for follicular lymphoma (FL)? Find out by accessing this activity, where an expert will interpret new evidence supporting the continued integration of bispecific antibodies, CAR-T cell therapy, EZH2 inhibitors, and PI3K inhibitors across multiple lines of therapy in relapsed/refractory FL. Throughout, the expert shares guidance on therapeutic sequencing, safety management, and the future use of innovative combination platforms. Don't miss this important update from ASH! Upon completion of this activity, participants should be better able to: Summarize evidence surrounding targeted, epigenetic, and immunotherapy options for R/R FL; Integrate modern, evidence-based sequential treatment plans for R/R FL that include immunomodulatory drugs, targeted therapies, epigenetic agents, bispecific antibodies, and CAR-T constructs; and Manage the unique suite of adverse events associated with the use of novel therapeutics as sequential management options in R/R FL
Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) published a new review paper in Volume 15, Issue 4, entitled, “Cellular senescence: when growth stimulation meets cell cycle arrest.” In this review, researcher Mikhail V. Blagosklonny, M.D., Ph.D., from Roswell Park Comprehensive Cancer Center discusses cellular senescence—a natural process that occurs as cells age and eventually stop dividing. Recent research has revealed that cellular senescence can also be triggered by hypertrophy and hyperfunctions. “At the very moment of cell-cycle arrest, the cell is not senescent yet. For several days in cell culture, the arrested cell is acquiring a senescent phenotype. What is happening during this geroconversion? Cellular enlargement (hypertrophy) and hyperfunctions (lysosomal and hyper-secretory) are hallmarks of geroconversion.” In his comprehensive review paper, Dr. Blagosklonny explores the complex relationship between growth stimulation and cell cycle arrest in cellular senescence. He discusses the various mechanisms that can lead to senescence, markers of senescence and geroconversion, and the importance of understanding these mechanisms and markers in the development of anti-aging drugs. “The same pathways that drive geroconversion are involved in organismal aging and age-related diseases. The same drugs that slow down geroconversion also extend lifespan, as tested in animals so far. Targets of gerostatics (e.g., mTOR, PI3K) are involved in aging of animals from worms to mammals. Therefore, gerostatics are anti-aging drugs. The model of geroconversion is useful to discover anti-aging drugs.” Dr. Blagosklonny is a renowned expert in the field of aging research. He has focused on the molecular mechanisms of aging, the hyperfunction theory of aging and the development of new drugs to combat age-related diseases. Dr. Blagosklonny's research, perspectives and reviews have made significant contributions to our understanding of aging. Full Paper: DOI: https://doi.org/10.18632/aging.204543 Corresponding Author: Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com, Blagosklonny@rapalogs.com Keywords: rapamycin, mTOR, hyperfunction theory of aging, cell volume and enlargement, gerogenic conversion Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204543
Go online to PeerView.com/SZT860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Are you up to date on the latest evidence with immunotherapy, targeted agents, and chemo-free options for follicular lymphoma (FL)? Find out by accessing this activity, where an expert will interpret new evidence supporting the continued integration of bispecific antibodies, CAR-T cell therapy, EZH2 inhibitors, and PI3K inhibitors across multiple lines of therapy in relapsed/refractory FL. Throughout, the expert shares guidance on therapeutic sequencing, safety management, and the future use of innovative combination platforms. Don't miss this important update from ASH! Upon completion of this activity, participants should be better able to: Summarize evidence surrounding targeted, epigenetic, and immunotherapy options for R/R FL; Integrate modern, evidence-based sequential treatment plans for R/R FL that include immunomodulatory drugs, targeted therapies, epigenetic agents, bispecific antibodies, and CAR-T constructs; and Manage the unique suite of adverse events associated with the use of novel therapeutics as sequential management options in R/R FL
Last week, senior editor Annalee Armstrong and staff writer Gabrielle Mason covered the Clinical Trials on Alzheimer's Disease conference. We'll hear from them as they discuss the latest news and what surprised them. Also in this episode, we cover the week's biggest headlines including an investigation into Neuralink, Google's DeepMind and why things aren't working out for PI3Ks. To learn more about topics in this episode: Eisai, Biogen rocked by 2nd lecanemab death report ahead of Alzheimer's data reveal Facing a familiar side effect problem, Eisai makes the case for its next Alzheimer's drug after patient deaths Roche thins Alzheimer's program after phase 3 failure, may seek 'external partnerships' A winner is crowned in head-to-head Alzheimer's battle between Biogen's Aduhelm and Lilly Neuralink under federal investigation for animal testing practices: Reuters Elon Musk claims Neuralink is 6 months from implanting brain-computer interfaces in humans—and, someday, he'll be one of them 'Troubling' study finds Google's kidney disease-predicting AI performs worse in women—and may not have a quick fix In fresh blow to floundering PI3K space, FDA feedback drives MEI, Kyowa to halt blood cancer program Rigel scores green light in AML just 4 months after buying asset from Forma UPDATED: J&J bows out of Horizon bid as Amgen and Sanofi eye cash plays for rare disease drugmaker Pfizer plots €1.2B investment—and up to 500 new jobs—at Irish manufacturing plant Fierce JPM Week "The Top Line" is produced by senior multimedia producer Teresa Carey with managing editor Querida Anderson and senior editors Annalee Armstrong, Ben Adams, Conor Hale and Eric Sagonowsky. The sound engineer is Caleb Hodgson. The stories are by all our “Fierce” journalists. Like and subscribe wherever you listen to your podcasts.See omnystudio.com/listener for privacy information.
Featuring an interview with Dr Brady Stein, including the following topics: Case: A man in his late 70s with myelofibrosis (MF) presenting with fatigue and night sweats (0:00) Incidence and severity of fatigue and other symptoms; use of symptom scales to measure severity (3:43) Rapidity of symptom response to ruxolitinib; emerging data with momelotinib (7:34) Novel therapeutic targets for MF: BET, PI3K and BCL2 (13:25) Available data on JAK inhibitors for essential thrombocytosis and polycythemia vera; pathogenesis of pruritus and optimal management (20:31) Clinical pearls on managing splenomegaly, weight loss and other MF symptoms (26:34) Risks of localized therapy for splenomegaly; splenic progression among patients receiving ruxolitinib (30:14) Prevention and management of withdrawal rebound from ruxolitinib; factors to consider in choosing JAK inhibitors for different risk groups (34:17) Myths and misperceptions about MF among community general oncologists (38:26) Management algorithms for transplant-eligible and transplant-ineligible patients (44:32) Current understanding of MF pathophysiology; end-of-life care for patients with MF (50:13) CME information and select publications
Go online to PeerView.com/DFJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Breast cancer is a heterogeneous disease comprising different subtypes, with estrogen receptor positive (ER+) being the most common subtype. Endocrine therapy (ET) is the primary treatment in ER+ breast cancer, which includes different strategies that directly or indirectly modify estrogen production. CDK4 and 6 inhibition as well as PI3K inhibition have improved outcomes in these patients, but most still develop endocrine resistance. ESR1 gene mutations, somatic alterations, microenvironmental factors, and epigenetic changes have all been implicated as underlying mechanisms promoting resistance. Novel ER-targeting agents such as oral selective estrogen receptor degraders (SERDs) are showing therapeutic promise in the face of ET resistance. In addition, other agents are being evaluated in ER+ disease, including selective estrogen receptor modifiers (SERMs), SERM/SERD hybrids, selective estrogen receptor covalent antagonists (SERCAs), proteolysis targeting chimeras (PROTACs), and others.This PeerView educational activity, based on a recent live symposium, highlights and analyzes the latest evidence and advances in the treatment of ER+/HER2- breast cancer, focusing on the expanding evidence base supporting the use of novel ER-targeted agents such as oral SERDs as a new standard of care in pretreated ER+/HER2- breast cancer. Practical guidance is also provided on how to apply the latest evidence to practice, optimize the use of these agents, and individualize treatment plans that take into account key data, patient- and tumor-related factors, and the specific needs and preferences of each patient. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including novel oral SERDs and other ER-targeting therapies, and their evolving role in clinical practice; Develop individualized treatment plans for patients with previously treated ER+/HER2- breast cancer that take into account the latest treatment options and all the relevant treatment-, tumor-, and patient-related factors; Integrate a team-based, collaborative, coordinated, and patient-centered approach to select appropriate candidates for SERDs and other new therapies for ER+/HER2- breast cancer, provide essential patient education, and ensure optimal delivery of therapy
Go online to PeerView.com/DFJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Breast cancer is a heterogeneous disease comprising different subtypes, with estrogen receptor positive (ER+) being the most common subtype. Endocrine therapy (ET) is the primary treatment in ER+ breast cancer, which includes different strategies that directly or indirectly modify estrogen production. CDK4 and 6 inhibition as well as PI3K inhibition have improved outcomes in these patients, but most still develop endocrine resistance. ESR1 gene mutations, somatic alterations, microenvironmental factors, and epigenetic changes have all been implicated as underlying mechanisms promoting resistance. Novel ER-targeting agents such as oral selective estrogen receptor degraders (SERDs) are showing therapeutic promise in the face of ET resistance. In addition, other agents are being evaluated in ER+ disease, including selective estrogen receptor modifiers (SERMs), SERM/SERD hybrids, selective estrogen receptor covalent antagonists (SERCAs), proteolysis targeting chimeras (PROTACs), and others.This PeerView educational activity, based on a recent live symposium, highlights and analyzes the latest evidence and advances in the treatment of ER+/HER2- breast cancer, focusing on the expanding evidence base supporting the use of novel ER-targeted agents such as oral SERDs as a new standard of care in pretreated ER+/HER2- breast cancer. Practical guidance is also provided on how to apply the latest evidence to practice, optimize the use of these agents, and individualize treatment plans that take into account key data, patient- and tumor-related factors, and the specific needs and preferences of each patient. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including novel oral SERDs and other ER-targeting therapies, and their evolving role in clinical practice; Develop individualized treatment plans for patients with previously treated ER+/HER2- breast cancer that take into account the latest treatment options and all the relevant treatment-, tumor-, and patient-related factors; Integrate a team-based, collaborative, coordinated, and patient-centered approach to select appropriate candidates for SERDs and other new therapies for ER+/HER2- breast cancer, provide essential patient education, and ensure optimal delivery of therapy
Go online to PeerView.com/DFJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Breast cancer is a heterogeneous disease comprising different subtypes, with estrogen receptor positive (ER+) being the most common subtype. Endocrine therapy (ET) is the primary treatment in ER+ breast cancer, which includes different strategies that directly or indirectly modify estrogen production. CDK4 and 6 inhibition as well as PI3K inhibition have improved outcomes in these patients, but most still develop endocrine resistance. ESR1 gene mutations, somatic alterations, microenvironmental factors, and epigenetic changes have all been implicated as underlying mechanisms promoting resistance. Novel ER-targeting agents such as oral selective estrogen receptor degraders (SERDs) are showing therapeutic promise in the face of ET resistance. In addition, other agents are being evaluated in ER+ disease, including selective estrogen receptor modifiers (SERMs), SERM/SERD hybrids, selective estrogen receptor covalent antagonists (SERCAs), proteolysis targeting chimeras (PROTACs), and others.This PeerView educational activity, based on a recent live symposium, highlights and analyzes the latest evidence and advances in the treatment of ER+/HER2- breast cancer, focusing on the expanding evidence base supporting the use of novel ER-targeted agents such as oral SERDs as a new standard of care in pretreated ER+/HER2- breast cancer. Practical guidance is also provided on how to apply the latest evidence to practice, optimize the use of these agents, and individualize treatment plans that take into account key data, patient- and tumor-related factors, and the specific needs and preferences of each patient. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including novel oral SERDs and other ER-targeting therapies, and their evolving role in clinical practice; Develop individualized treatment plans for patients with previously treated ER+/HER2- breast cancer that take into account the latest treatment options and all the relevant treatment-, tumor-, and patient-related factors; Integrate a team-based, collaborative, coordinated, and patient-centered approach to select appropriate candidates for SERDs and other new therapies for ER+/HER2- breast cancer, provide essential patient education, and ensure optimal delivery of therapy
Go online to PeerView.com/DFJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Breast cancer is a heterogeneous disease comprising different subtypes, with estrogen receptor positive (ER+) being the most common subtype. Endocrine therapy (ET) is the primary treatment in ER+ breast cancer, which includes different strategies that directly or indirectly modify estrogen production. CDK4 and 6 inhibition as well as PI3K inhibition have improved outcomes in these patients, but most still develop endocrine resistance. ESR1 gene mutations, somatic alterations, microenvironmental factors, and epigenetic changes have all been implicated as underlying mechanisms promoting resistance. Novel ER-targeting agents such as oral selective estrogen receptor degraders (SERDs) are showing therapeutic promise in the face of ET resistance. In addition, other agents are being evaluated in ER+ disease, including selective estrogen receptor modifiers (SERMs), SERM/SERD hybrids, selective estrogen receptor covalent antagonists (SERCAs), proteolysis targeting chimeras (PROTACs), and others.This PeerView educational activity, based on a recent live symposium, highlights and analyzes the latest evidence and advances in the treatment of ER+/HER2- breast cancer, focusing on the expanding evidence base supporting the use of novel ER-targeted agents such as oral SERDs as a new standard of care in pretreated ER+/HER2- breast cancer. Practical guidance is also provided on how to apply the latest evidence to practice, optimize the use of these agents, and individualize treatment plans that take into account key data, patient- and tumor-related factors, and the specific needs and preferences of each patient. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including novel oral SERDs and other ER-targeting therapies, and their evolving role in clinical practice; Develop individualized treatment plans for patients with previously treated ER+/HER2- breast cancer that take into account the latest treatment options and all the relevant treatment-, tumor-, and patient-related factors; Integrate a team-based, collaborative, coordinated, and patient-centered approach to select appropriate candidates for SERDs and other new therapies for ER+/HER2- breast cancer, provide essential patient education, and ensure optimal delivery of therapy
Go online to PeerView.com/DFJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Breast cancer is a heterogeneous disease comprising different subtypes, with estrogen receptor positive (ER+) being the most common subtype. Endocrine therapy (ET) is the primary treatment in ER+ breast cancer, which includes different strategies that directly or indirectly modify estrogen production. CDK4 and 6 inhibition as well as PI3K inhibition have improved outcomes in these patients, but most still develop endocrine resistance. ESR1 gene mutations, somatic alterations, microenvironmental factors, and epigenetic changes have all been implicated as underlying mechanisms promoting resistance. Novel ER-targeting agents such as oral selective estrogen receptor degraders (SERDs) are showing therapeutic promise in the face of ET resistance. In addition, other agents are being evaluated in ER+ disease, including selective estrogen receptor modifiers (SERMs), SERM/SERD hybrids, selective estrogen receptor covalent antagonists (SERCAs), proteolysis targeting chimeras (PROTACs), and others.This PeerView educational activity, based on a recent live symposium, highlights and analyzes the latest evidence and advances in the treatment of ER+/HER2- breast cancer, focusing on the expanding evidence base supporting the use of novel ER-targeted agents such as oral SERDs as a new standard of care in pretreated ER+/HER2- breast cancer. Practical guidance is also provided on how to apply the latest evidence to practice, optimize the use of these agents, and individualize treatment plans that take into account key data, patient- and tumor-related factors, and the specific needs and preferences of each patient. Upon completion of this activity, participants should be better able to: Describe the rationale, mechanisms of action, and latest efficacy and safety data of approved and emerging treatment options for patients with ER+/HER2- breast cancer, including novel oral SERDs and other ER-targeting therapies, and their evolving role in clinical practice; Develop individualized treatment plans for patients with previously treated ER+/HER2- breast cancer that take into account the latest treatment options and all the relevant treatment-, tumor-, and patient-related factors; Integrate a team-based, collaborative, coordinated, and patient-centered approach to select appropriate candidates for SERDs and other new therapies for ER+/HER2- breast cancer, provide essential patient education, and ensure optimal delivery of therapy
VIDEOS : WES2022 | Yuval Noah Harari and Vanessa Nakate in conversation (3:19) Why Colleges Are Becoming Cults [Full Series] | Dr. Lyell Asher (15:00 to 43:42 Gary Null Speaking Out at the NYS Assembly Hearing (25:00) Astragulus found to inhibit breast cancer cell proliferation Fujian University of Traditional Medicine (China), September 8, 2022 Huang qi (Astragalus) is one of the fundamental herbs in traditional Chinese medicine, with earliest records of its use dating back over 2,000 years ago. Now, a study in BMC Complementary and Alternative Medicine has found that astragulus is also able to prevent the spread of breast cancer cells in the body. In the study, researchers from the Fujian University of Traditional Chinese Medicine in China looked at how astragulus extract can affect breast cancer cells and the process behind this biological effect. They also looked at the primary isoflavones in the extract, as well as its anti-proliferative activity on three breast cancer lines: MCF-7 (ER+), SK-BR-3 (HER2+) and MDA-MB-231 (triple-negative). They did this by exposing these breast cancer cells to the extract for 48 hours. In addition, they examined the effect of astragulus extract on phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways, a primary intracellular signaling pathway that contributes to cell proliferation, growth, migration, metabolism, and apoptosis. The results of the study showed that the treatment of astragulus exhibited anti-proliferative activity on breast cancer cells. Furthermore, the therapy promoted the death of breast cancer cells. These suggested that it's ability to inhibit breast cancer cell growth was linked to its ability to inhibit PI3K/Akt/mTOR activity. Moreover, the researchers found that the Huang qi extract contains four types of isoflavones, such as campanulin, ononin, calycosin, and formononetin, which contributed to the inhibitory effect of Huang qi extract on breast cancer cells proliferation. Vitamin D supplementation could help critically ill patients University Hospital Würzburg (Germany) September 12 2022. Findings from a review and meta-analysis reported in Critical Care suggest that providing critically ill patients with vitamin D supplements may improve some clinical outcomes, including survival. “Upon ICU admission, the majority of patients have significantly reduced 25-hydroxyvitamin D levels, which remain significantly reduced over the entire ICU length of stay,” Johannes Menger and colleagues wrote. “In these patients, significantly reduced vitamin D (25-hydroxyvitamin D) serum levels are frequent and independently associated with higher incidence and severity of sepsis.” Sixteen randomized, controlled trials that evaluated vitamin D supplementation's association with mortality were identified. Vitamin D supplementation was associated with a 22% lower risk of overall mortality in comparison with a placebo or standard care. Among studies that reported 28-day mortality, vitamin D supplementation was associated with a trend toward lower a lower risk. Receiving vitamin D by injection or intravenously had the strongest effect. Patients who received vitamin D spent an average of 3.13 days less in the ICU and 5 fewer days on a ventilator than those who received a placebo. “The results of this systematic review and meta-analysis suggest that vitamin D supplementation may be associated with reduced overall mortality in critically ill patients,” they concluded. Natural compound could reduce breast cancer risk in some women Luteolin may inhibit growth of human breast cancer cells in postmenopausal women taking hormone replacement therapy University of Missouri-Columbia, September 9, 2022 More than 100 women die from breast cancer every day in the United States. The odds increase in postmenopausal women who have taken a combined estrogen and progestin hormone replacement therapy; these women also have an increased risk of developing progestin-accelerated breast tumors. Now, University of Missouri researchers have found that luteolin, a natural compound found in herbs such as thyme and parsley as well as vegetables such as celery and broccoli, could reduce the cancer risk for women who have taken hormone replacement therapy. “Most older women normally have benign lesions in breast tissue,” Hyder said. “These lesions typically don't form tumors until they receive the ‘trigger'– in this case, progestin–that attracts blood vessels to cells essentially feeding the lesions causing them to expand.” His newest study shows that when the supplement luteolin is administered to human breast cancer cells in the lab, benefits can be observed including the reduction of those vessels “feeding” the cancer cells causing cancer cell death. Hyder's lab has found that as human breast cancer cells develop, they tend to take on stem cell-like properties, which can make them harder to kill. Here, luteolin was used to monitor stem cell-like characteristics of breast cancer cells and his team saw a vast reduction in this phenomenon, further proving that the natural compound exerts its anti-tumor effects in a variety of ways. “We feel that luteolin can be effective when injected directly into the bloodstream, so IV supplements may still be a possibility,” Hyder said. “But, until the supplement is tested for safety and commercialized, which we hope will happen after further testing and clinical trials, women should continue consuming a healthy diet with fresh fruits and vegetables.” CBD shows health benefits in estrogen-deficient mice that model postmenopause Rutgers University, September 14, 2022 A Rutgers study points to cannabidiol (CBD), a major component of hemp and medical marijuana used to treat conditions such as chronic pain, inflammation, migraines, epilepsy, autoimmune diseases, depression, and anxiety, as a possible treatment for postmenopausal women whose ovaries no longer make estrogen. In a study published in Frontiers in Pharmacology, scientists reported that when estrogen-deficient mice were fed CBD, a non-intoxicating compound extracted from hemp, they showed marked improvement in several areas. Their bloodstreams more readily disposed of glucose, and they burned more energy. In addition, their bone density improved, they had less inflammation in gut and bone tissues and they possessed higher levels of beneficial gut bacteria. “This preclinical study is the first to suggest the therapeutic potential of CBD for alleviating symptoms of estrogen deficiency,” said Diana Roopchand, an assistant professor in the Department of Food Science of the Rutgers School of Environmental and Biological Sciences (SEBS) and senior author on the study. “There is much anecdotal evidence of CBD's health benefits for menopausal and postmenopausal women, but our study is the first to investigate some of the claims in an established preclinical model of postmenopause.” Over 18 weeks, researchers fed the estrogen-deficient mice a steady diet of either tiny, CBD-laced peanut butter balls or peanut butter balls without CBD. The untreated estrogen-deficient mice developed symptoms that resembled those of postmenopausal human females, such as metabolic dysfunction, evidence of inflammation, lower bone density, and lower levels of beneficial gut bacteria. However, in mice that ingested CBD, these conditions were significantly improved. Mediterranean diet and depression among older individuals Harokopio University (Greece), September 9, 2022 According to news originating from Athens, Greece,research stated, “In Europe, depression is one of the most frequent mental disorders across all age groups, but particularly in people aged 65 years and over, and higher depressive symptoms have been reported among individuals with chronic diseases (e.g., diabetes and heart disease).” Research from Harokopio University stated, “To evaluate the role of adherence to the Mediterranean diet (MedDiet) in depression in a sample of older people living in the Mediterranean basin. Standard procedures were used to determine socio-demographic, lifestyle, and clinical characteristics of the participants, as well as their dietary habits, and depressive symptoms were evaluated using the Geriatric Depression Scale (GDS). Participants classified as having mild or severe depression were less educated and physically active, and more diabetic, and they reported less adherence to the MedDiet. Adherence to the MedDiet was associated with the absence of depression [(OR, 95% CI): 0.65, 0.50 – 0.85]. In addition, daily tea drinking was also related to the absence of depression [(OR, 95% CI): 0.51, 0.40 – 0.65].” According to the news editors, the research concluded: “Greater adherence to the MedDiet and daily tea drinking seem to have a beneficial effect on depressive symptoms in older adults.” High cholesterol leads to long-term liver scarring and immune cell dysfunction in lab study University of Southern California, September 15, 2022 There's a long-established link between a high-fat, high-sugar diet and fatty liver disease, which can lead to life-threatening conditions such as cirrhosis and liver cancer. Now, new research from the Keck School of Medicine of USC adds some detail and dimension to this picture. The lab study, published in Frontiers in Immunology, is the first-ever to focus on how different amounts of cholesterol as part of a diet high in fat and sugar affect fatty liver disease progression. Modeling the disease in mice, the investigators demonstrated that high cholesterol intake can make fatty liver disease worse—driving inflammation and scarring—and that, importantly, scar tissuecan persist even after switching to a diet low in cholesterol. The findings also indicated that a high-cholesterol diet can create long-lasting dysfunction in a specific population of immune cells previously shown to play a role in fatty liver disease. “We saw that you may have a high-fat and high-sugar diet, but when you add high cholesterol to that, it will accelerate the process that causes inflammation in your liver,” said corresponding author Ana Maretti-Mira, Ph.D., an assistant research professor of medicine at USC. “People focus on high cholesterol as a risk for heart disease, but we showed that your liver may also be affected, causing inflammation, scarring and, potentially, cirrhosis.” High cholesterol makes fatty liver disease worse The researchers fed mice a high-fat, high-sugar diet shown to cause a form of advanced fatty liver disease similar to human illness. The mice were split into three groups that received different amounts of cholesterol in their food for 20 weeks—midlife for the animals. The low-cholesterol group received one-quarter the cholesterol compared to medium; the high-cholesterol group received 25 times more than the low-cholesterol group. After 20 weeks, the livers of mice from all three groups showed accumulation of fat, a benign feature of fatty liver disease, but the high-cholesterol group had more advanced disease, with increased inflammation and scar tissue. For the following 10 weeks, mice from all three groups received low cholesterol as part of a diet that remained high in fat and sugar. At the end of that time, that change in diet had reversed inflammation in the original high-cholesterol mice, but had not reduced scar tissue. This finding shows that damage caused by high cholesterol can be hard to undo. The high-fat, high-sugar diet given to mice in the study has unfortunate similarities to the typical Western diet in humans. “Our daily diet has lots of carbohydrates, such as sugary drinks, bread, rice and pasta,” Maretti-Mira said. “Then there's high fat, since everybody likes deep fried foods. At the same time, we don't have the same active life we used to, so we end up eating much more than our body needs.”
A new research paper was published in Oncotarget on August 4, 2022, entitled, “Kinase activity profiling in renal cell carcinoma, benign renal tissue and in response to four different tyrosine kinase inhibitors.” Kinase activity is frequently altered in renal cell carcinoma (RCC), and tyrosine kinase inhibitors (TKIs) are part of the standard treatment strategy in patients with metastatic disease. However, there are still no established biomarkers to predict clinical benefits of a specific TKI. “Despite a number of new treatment options improving RCC patients' disease control rates and survival, the lack of useful biomarkers remains a major clinical concern.” In the current study, researchers Andliena Tahiri, Katarina Puco, Faris Naji, Vessela N. Kristensen, Glenny Cecilie Alfsen, Lorant Farkas, Frode S. Nilsen, Stig Müller, Jan Oldenburg, and Jürgen Geisler, from University of Oslo, Oslo University Hospital, Akershus University Hospital, and Pamgene International BV, performed protein tyrosine kinase (PTK) profiling using PamChip® technology. “The aim of this study was to identify differences in PTK activity between normal and malignant kidney tissue obtained from the same patient, and to investigate the inhibitory effects of TKIs frequently used in the clinics: sunitinib, pazopanib, cabozantinib and tivozanib.” The results showed that 36 kinase substrates differ (FDR < 0.05) between normal and cancer kidney tissue, where members of the Src family kinases and the phosphoinositide-3-kinase (PI3K) pathway exhibit high activity in renal cancer. Furthermore, ex vivo treatment of clear cell RCC with TKIs revealed that pathways such as Rap1, Ras and PI3K pathways were strongly inhibited, whereas the neurotrophin pathway had increased activity upon TKI addition. Their assay showed that tivozanib and cabozantinib exhibited greater inhibitory effects on PTK activity compared to sunitinib and pazopanib, implying they might be better suitable as TKIs for selected RCC patients. “The results of our study contribute to better understanding of the changes in kinase activity in RCC tumor cells involved in fundamental oncogenic cellular processes and the ex vivo effect of TKIs. We found tivozanib and cabozantinib to be more potent TKIs in RCC samples than sunitinib or pazopanib. The next step will be to correlate the efficacy and toxicity in individual patients with their respective kinase activity of normal and malignant kidney tissue.” DOI: https://doi.org/10.18632/oncotarget.28257 Correspondence to: Jürgen Geisler – Email: juergen.geisler@medisin.uio.no Keywords: kidney cancer, kinase activity, tyrosine kinase inhibitors, renal cell carcinoma, tyrosine kinase About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
Go online to PeerView.com/NDA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Are you ready to make personalized treatment choices with the potent suite of targeted agents, including BTK and BCL-2 inhibitors, that have become standards of care in chronic lymphocytic leukemia (CLL)? In collaboration with the CLL Society, this PeerView MasterClass & Case Forum, based on a live event at the ASCO Annual Meeting, will give learners foundational insights on the evidence that supports the use of personalized therapy with modern targeted platforms. Watch the expert panel present a series of highly practical case discussions that include guidance on: the evidence-based selection of treatment strategies for treatment-naïve and relapsed CLL; therapeutic planning based on safety considerations; and the integration of novel combinatorial and cellular therapy strategies. Don't miss this expert-led program and receive CME/MOC credit! Upon completion of this activity, participants should be better able to: Summarize updated efficacy and safety evidence supporting the integration of novel therapeutic classes in CLL, including evidence with BTK, PI3K, and BCL-2 inhibitors, novel combinations, and CAR-T options; Recommend personalized treatment with targeted agents, including fixed duration or continuous therapy strategies or appropriate combinatorial or sequential options, for patients presenting with treatment-naïve or relapsed/refractory CLL; and Manage unique safety considerations associated with the use of targeted agents, novel antibodies, or cellular therapies in the CLL setting.
Go online to PeerView.com/NDA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Are you ready to make personalized treatment choices with the potent suite of targeted agents, including BTK and BCL-2 inhibitors, that have become standards of care in chronic lymphocytic leukemia (CLL)? In collaboration with the CLL Society, this PeerView MasterClass & Case Forum, based on a live event at the ASCO Annual Meeting, will give learners foundational insights on the evidence that supports the use of personalized therapy with modern targeted platforms. Watch the expert panel present a series of highly practical case discussions that include guidance on: the evidence-based selection of treatment strategies for treatment-naïve and relapsed CLL; therapeutic planning based on safety considerations; and the integration of novel combinatorial and cellular therapy strategies. Don't miss this expert-led program and receive CME/MOC credit! Upon completion of this activity, participants should be better able to: Summarize updated efficacy and safety evidence supporting the integration of novel therapeutic classes in CLL, including evidence with BTK, PI3K, and BCL-2 inhibitors, novel combinations, and CAR-T options; Recommend personalized treatment with targeted agents, including fixed duration or continuous therapy strategies or appropriate combinatorial or sequential options, for patients presenting with treatment-naïve or relapsed/refractory CLL; and Manage unique safety considerations associated with the use of targeted agents, novel antibodies, or cellular therapies in the CLL setting.
Go online to PeerView.com/JJJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Are you ready to make personalized treatment choices with the potent suite of targeted agents, including BTK and BCL-2 inhibitors, that have become standards of care in chronic lymphocytic leukemia (CLL)? In collaboration with the CLL Society, this PeerView MasterClass & Case Forum, based on a live event at the ASCO Annual Meeting, will give learners foundational insights on the evidence that supports the use of personalized therapy with modern targeted platforms. Watch the expert panel present a series of highly practical case discussions that include guidance on: the evidence-based selection of treatment strategies for treatment-naïve and relapsed CLL; therapeutic planning based on safety considerations; and the integration of novel combinatorial and cellular therapy strategies. Don't miss this expert-led program and receive CME/MOC credit! Upon completion of this activity, participants should be better able to: Summarize updated efficacy and safety evidence supporting the integration of novel therapeutic classes in CLL, including evidence with BTK, PI3K, and BCL-2 inhibitors, novel combinations, and CAR-T options; Recommend personalized treatment with targeted agents, including fixed duration or continuous therapy strategies or appropriate combinatorial or sequential options, for patients presenting with treatment-naïve or relapsed/refractory CLL; and Manage unique safety considerations associated with the use of targeted agents, novel antibodies, or cellular therapies in the CLL setting.
Go online to PeerView.com/JJJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Are you ready to make personalized treatment choices with the potent suite of targeted agents, including BTK and BCL-2 inhibitors, that have become standards of care in chronic lymphocytic leukemia (CLL)? In collaboration with the CLL Society, this PeerView MasterClass & Case Forum, based on a live event at the ASCO Annual Meeting, will give learners foundational insights on the evidence that supports the use of personalized therapy with modern targeted platforms. Watch the expert panel present a series of highly practical case discussions that include guidance on: the evidence-based selection of treatment strategies for treatment-naïve and relapsed CLL; therapeutic planning based on safety considerations; and the integration of novel combinatorial and cellular therapy strategies. Don't miss this expert-led program and receive CME/MOC credit! Upon completion of this activity, participants should be better able to: Summarize updated efficacy and safety evidence supporting the integration of novel therapeutic classes in CLL, including evidence with BTK, PI3K, and BCL-2 inhibitors, novel combinations, and CAR-T options; Recommend personalized treatment with targeted agents, including fixed duration or continuous therapy strategies or appropriate combinatorial or sequential options, for patients presenting with treatment-naïve or relapsed/refractory CLL; and Manage unique safety considerations associated with the use of targeted agents, novel antibodies, or cellular therapies in the CLL setting.
Go online to PeerView.com/JJJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Are you ready to make personalized treatment choices with the potent suite of targeted agents, including BTK and BCL-2 inhibitors, that have become standards of care in chronic lymphocytic leukemia (CLL)? In collaboration with the CLL Society, this PeerView MasterClass & Case Forum, based on a live event at the ASCO Annual Meeting, will give learners foundational insights on the evidence that supports the use of personalized therapy with modern targeted platforms. Watch the expert panel present a series of highly practical case discussions that include guidance on: the evidence-based selection of treatment strategies for treatment-naïve and relapsed CLL; therapeutic planning based on safety considerations; and the integration of novel combinatorial and cellular therapy strategies. Don't miss this expert-led program and receive CME/MOC credit! Upon completion of this activity, participants should be better able to: Summarize updated efficacy and safety evidence supporting the integration of novel therapeutic classes in CLL, including evidence with BTK, PI3K, and BCL-2 inhibitors, novel combinations, and CAR-T options; Recommend personalized treatment with targeted agents, including fixed duration or continuous therapy strategies or appropriate combinatorial or sequential options, for patients presenting with treatment-naïve or relapsed/refractory CLL; and Manage unique safety considerations associated with the use of targeted agents, novel antibodies, or cellular therapies in the CLL setting.
Go online to PeerView.com/JJJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Are you ready to make personalized treatment choices with the potent suite of targeted agents, including BTK and BCL-2 inhibitors, that have become standards of care in chronic lymphocytic leukemia (CLL)? In collaboration with the CLL Society, this PeerView MasterClass & Case Forum, based on a live event at the ASCO Annual Meeting, will give learners foundational insights on the evidence that supports the use of personalized therapy with modern targeted platforms. Watch the expert panel present a series of highly practical case discussions that include guidance on: the evidence-based selection of treatment strategies for treatment-naïve and relapsed CLL; therapeutic planning based on safety considerations; and the integration of novel combinatorial and cellular therapy strategies. Don't miss this expert-led program and receive CME/MOC credit! Upon completion of this activity, participants should be better able to: Summarize updated efficacy and safety evidence supporting the integration of novel therapeutic classes in CLL, including evidence with BTK, PI3K, and BCL-2 inhibitors, novel combinations, and CAR-T options; Recommend personalized treatment with targeted agents, including fixed duration or continuous therapy strategies or appropriate combinatorial or sequential options, for patients presenting with treatment-naïve or relapsed/refractory CLL; and Manage unique safety considerations associated with the use of targeted agents, novel antibodies, or cellular therapies in the CLL setting.
Go online to PeerView.com/JJJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Are you ready to make personalized treatment choices with the potent suite of targeted agents, including BTK and BCL-2 inhibitors, that have become standards of care in chronic lymphocytic leukemia (CLL)? In collaboration with the CLL Society, this PeerView MasterClass & Case Forum, based on a live event at the ASCO Annual Meeting, will give learners foundational insights on the evidence that supports the use of personalized therapy with modern targeted platforms. Watch the expert panel present a series of highly practical case discussions that include guidance on: the evidence-based selection of treatment strategies for treatment-naïve and relapsed CLL; therapeutic planning based on safety considerations; and the integration of novel combinatorial and cellular therapy strategies. Don't miss this expert-led program and receive CME/MOC credit! Upon completion of this activity, participants should be better able to: Summarize updated efficacy and safety evidence supporting the integration of novel therapeutic classes in CLL, including evidence with BTK, PI3K, and BCL-2 inhibitors, novel combinations, and CAR-T options; Recommend personalized treatment with targeted agents, including fixed duration or continuous therapy strategies or appropriate combinatorial or sequential options, for patients presenting with treatment-naïve or relapsed/refractory CLL; and Manage unique safety considerations associated with the use of targeted agents, novel antibodies, or cellular therapies in the CLL setting.
Go online to PeerView.com/JJJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Are you ready to make personalized treatment choices with the potent suite of targeted agents, including BTK and BCL-2 inhibitors, that have become standards of care in chronic lymphocytic leukemia (CLL)? In collaboration with the CLL Society, this PeerView MasterClass & Case Forum, based on a live event at the ASCO Annual Meeting, will give learners foundational insights on the evidence that supports the use of personalized therapy with modern targeted platforms. Watch the expert panel present a series of highly practical case discussions that include guidance on: the evidence-based selection of treatment strategies for treatment-naïve and relapsed CLL; therapeutic planning based on safety considerations; and the integration of novel combinatorial and cellular therapy strategies. Don't miss this expert-led program and receive CME/MOC credit! Upon completion of this activity, participants should be better able to: Summarize updated efficacy and safety evidence supporting the integration of novel therapeutic classes in CLL, including evidence with BTK, PI3K, and BCL-2 inhibitors, novel combinations, and CAR-T options; Recommend personalized treatment with targeted agents, including fixed duration or continuous therapy strategies or appropriate combinatorial or sequential options, for patients presenting with treatment-naïve or relapsed/refractory CLL; and Manage unique safety considerations associated with the use of targeted agents, novel antibodies, or cellular therapies in the CLL setting.
A new research paper was published in Oncotarget on July 19, 2022, entitled, “CUDC907, a dual phosphoinositide-3 kinase/histone deacetylase inhibitor, promotes apoptosis of NF2 Schwannoma cells.” Neurofibromatosis Type 2 (NF2) is a rare tumor disorder caused by pathogenic variants of the merlin tumor suppressor encoded by NF2. Patients develop vestibular schwannomas (VS), peripheral schwannomas, meningiomas, and ependymomas. There are no approved drug therapies for NF2. Previous work identified phosphoinositide-3 kinase (PI3K) as a druggable target. Researchers Julianne Huegel, Christine T. Dinh, Maria Martinelli, Olena Bracho, Rosa Rosario, Haley Hardin, Michael Estivill, Anthony Griswold, Sakir Gultekin, Xue-Zhong Liu, and Cristina Fernandez-Valle, from the University of Central Florida and the University of Miami Miller School of Medicine, conducted an unbiased chemical compound screen of the Library of Pharmacologically Active Compounds (LOPAC) as a pilot high-throughput screen to identify NF2 schwannoma targets for inhibition. “Here we screened PI3K pathway inhibitors for efficacy in reducing viability of human schwannoma cells.” The lead compound, CUDC907, a dual histone deacetylase (HDAC)/PI3K inhibitor, was further evaluated for its effects on isolated and nerve-grafted schwannoma model cells, and primary VS cells. CUDC907 (3 nM IG50) reduced human merlin deficient Schwann cell (MD-SC) viability and was 5–100 fold selective for MD over WT-SCs. CUDC907 (10 nM) promoted cell cycle arrest and caspase-3/7 activation within 24 hours in human MD-SCs. Western blots confirmed a dose-dependent increase in acetylated lysine and decreases in pAKT and YAP. In a 14-day treatment regimen, CUDC907 decreased tumor growth rate by 44%, modulated phospho-target levels, and decreased YAP levels. In five primary VS, CUDC907 decreased viability, induced caspase-3/7 cleavage, and reduced YAP levels. Its efficacy correlated with basal phospho-HDAC2 levels. CUDC907 has cytotoxic activity in NF2 schwannoma models and primary VS cells and is a candidate for clinical trials. “In summary, we demonstrated that CUDC907 reduced the activity of three major signaling pathways in NF2 schwannomas (HDAC, PI3K, and YAP) and consistently reduced viability and induced apoptosis in several schwannoma cell models and in all five genetically unique primary VS studied. These consistent results offer the possibility that CUDC907 will promote schwannoma regression in patients with diverse NF2 mutations and support clinical evaluation of CUDC907 for NF2-associated schwannomas and potentially other cancers driven by NF2 pathogenic variants [45]. Current use of this drug in clinical trials for other indications reveals clinical interest in multi-modal drugs over monotherapies.” DOI: https://doi.org/10.18632/oncotarget.28254 Correspondence to: Cristina Fernandez-Valle – Email: cfv@ucf.edu Keywords: fimepinostat, Schwann cell, vestibular schwanomma, merlin, nerve allograft About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
Go online to PeerView.com/AFW860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Pharmacists have a central role in the management of chronic lymphocytic leukemia (CLL) and the delivery of potent targeted agents. How will new evidence influence the core tenets of pharmacy practice? In this activity, a leukemia clinical pharmacy specialist provides answers through a precise review of the newest targeted therapy standards for CLL. This program includes insights on the latest efficacy evidence and regulatory status of targeted agents in CLL, while addressing drug interactions, treatment adherence, safety considerations, dosing, and care coordination. Upon completion of this activity, participants should be better able to: Summarize the current treatment role, efficacy and safety evidence, and regulatory status of targeted therapy in CLL, including BTK, BCL-2, and PI3K inhibitors, Educate patients and clinical staff about potential drug–drug interactions, and appropriate dosing, safety, and drug delivery considerations related to the use of targeted agents for CLL, Apply team-based approaches to integrate novel therapies into customized CLL management while addressing drug interactions, adherence, safety, dosing, and care coordination.
Go online to PeerView.com/GUR860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Gain the skills you need to adapt your current management protocols to reflect the new treatment reality in chronic lymphocytic leukemia (CLL), utilize novel combinatorial and sequential strategies, and map out the role of emerging cell-based therapies! In this activity, expert hematologist-oncologists provide expert guidance on the transformed nature of modern CLL management, the practice-changing evidence that validated targeted therapy platforms, and the science that is redefining the roles of hematopoietic stem cell transplantation and cellular therapy, including in challenging pretreated CLL settings. Upon completion of this activity, participants should be better able to: Cite current guidelines and evidence on the treatment roles of hematopoietic stem cell transplantation; BTK, PI3K, and BCL-2 inhibitors; monoclonal antibodies; and CAR-T cell therapy in the CLL setting, Discuss evidence surrounding the efficacy and safety of novel therapeutics across the spectrum of CLL, including in higher-risk disease settings or in patients relapsing after multiple prior treatments, Recommend regimens with novel components for patients presenting with treatment-naïve, high-risk, or relapsed/refractory CLL.
Go online to PeerView.com/AFW860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Pharmacists have a central role in the management of chronic lymphocytic leukemia (CLL) and the delivery of potent targeted agents. How will new evidence influence the core tenets of pharmacy practice? In this activity, a leukemia clinical pharmacy specialist provides answers through a precise review of the newest targeted therapy standards for CLL. This program includes insights on the latest efficacy evidence and regulatory status of targeted agents in CLL, while addressing drug interactions, treatment adherence, safety considerations, dosing, and care coordination. Upon completion of this activity, participants should be better able to: Summarize the current treatment role, efficacy and safety evidence, and regulatory status of targeted therapy in CLL, including BTK, BCL-2, and PI3K inhibitors, Educate patients and clinical staff about potential drug–drug interactions, and appropriate dosing, safety, and drug delivery considerations related to the use of targeted agents for CLL, Apply team-based approaches to integrate novel therapies into customized CLL management while addressing drug interactions, adherence, safety, dosing, and care coordination.
Go online to PeerView.com/GUR860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Gain the skills you need to adapt your current management protocols to reflect the new treatment reality in chronic lymphocytic leukemia (CLL), utilize novel combinatorial and sequential strategies, and map out the role of emerging cell-based therapies! In this activity, expert hematologist-oncologists provide expert guidance on the transformed nature of modern CLL management, the practice-changing evidence that validated targeted therapy platforms, and the science that is redefining the roles of hematopoietic stem cell transplantation and cellular therapy, including in challenging pretreated CLL settings. Upon completion of this activity, participants should be better able to: Cite current guidelines and evidence on the treatment roles of hematopoietic stem cell transplantation; BTK, PI3K, and BCL-2 inhibitors; monoclonal antibodies; and CAR-T cell therapy in the CLL setting, Discuss evidence surrounding the efficacy and safety of novel therapeutics across the spectrum of CLL, including in higher-risk disease settings or in patients relapsing after multiple prior treatments, Recommend regimens with novel components for patients presenting with treatment-naïve, high-risk, or relapsed/refractory CLL.
Go online to PeerView.com/GUR860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Gain the skills you need to adapt your current management protocols to reflect the new treatment reality in chronic lymphocytic leukemia (CLL), utilize novel combinatorial and sequential strategies, and map out the role of emerging cell-based therapies! In this activity, expert hematologist-oncologists provide expert guidance on the transformed nature of modern CLL management, the practice-changing evidence that validated targeted therapy platforms, and the science that is redefining the roles of hematopoietic stem cell transplantation and cellular therapy, including in challenging pretreated CLL settings. Upon completion of this activity, participants should be better able to: Cite current guidelines and evidence on the treatment roles of hematopoietic stem cell transplantation; BTK, PI3K, and BCL-2 inhibitors; monoclonal antibodies; and CAR-T cell therapy in the CLL setting, Discuss evidence surrounding the efficacy and safety of novel therapeutics across the spectrum of CLL, including in higher-risk disease settings or in patients relapsing after multiple prior treatments, Recommend regimens with novel components for patients presenting with treatment-naïve, high-risk, or relapsed/refractory CLL.
Videos: 1. Klaus Schwab — A Conversation With Albert Bourla, CEO of Pfizer (play 3:00 mins) 2. Ft. Daniel Nolan – Speaking about misinformation and Truth (19:00) 3. This Western priest can afford to speak frankly. He has nothing to lose and no one to fear (2:29) 4. You heard it from Mr Twitter himself – Elon Musk (0:43) 5. FDA Limits J&J Vaccine “Trust the science “ – ABC News Clip (0:27) 6. What is Monkeypox and Was It Planned For A Year Ago – Ben Swann (6:34) 7. Ivory Hecker – Americans are done panicking about viruses. 8. Bill Gates – ” We didn't understand that it's a fairly low fatality rate” (0:30) Articles of Interest: FBI Conducted Potentially Millions of Searches of Americans' Data Last Year, Report Says I FOUND IT!!! Why do Ukrainians tie people to poles? Antioxidant-rich grape powder protects brain from damage caused by high fat and high sugar diets: Study Taipei Medical University (Taiwan), May 17, 2022 Antioxidants from grape powder helped ease hyperglycaemia-related cognitive dysfunction in aged rats, a study discovered. Researchers from the Taipei Medical University said polyphenols from grape powder produced antioxidative and blood sugar-lowering properties that reduced the damage caused by a high-fat-high-fructose (HFHF) diet. Findings revealed that 6% grape powder group had reduced RAGE, or receptor for advanced glycation end products in the brain tissue. “Inclusion of up to 6% grape powder in the diet markedly reduced RAGE expression and tau hyperphosphorylation, but upregulated the expression of Nrf2 and BDNF, as well as the phosphorylation of PI3K and ERK, in the brain tissues of aged rats fed the HFHF diet,” the researchers reported. Thus, while long-term diet high in fructose and fat levels can cause hyperglycemia-related cognitive dysfunction in aged rats, grape powder supplementation can help ease the damaging changes in the brain protein related to neurodegeneration. Excessive degradation of mitochondria is the tipping point from normal alcohol metabolism to alcoholic liver disease Medical University of South Carolina, May 24, 2022 While most commonly known as “the powerhouses of the cell” because of their energy producing capabilities, mitochondria also play important roles in regulating the health of cells. These important structures can be damaged by alcohol consumption, which can cause them to rupture and release their DNA, proteins and lipids, collectively known as “damage associated molecular patterns (DAMPs).” To understand more fully how alcohol damages mitochondria, and how this leads to mitophagy, researchers at the Medical University of South Carolina (MUSC) used an advanced imaging technique to investigate changes in mitochondrial function within the livers of mice that were exposed to alcohol. Their findings, published online on March 16 in the journal Autophagy, demonstrated that exposure to alcohol causes a specific type of mitochondrial damage called depolarization. In a completely novel discovery, they found that it is this depolarization that indicates to the cell that the mitochondria are damaged and thereby causes activation of the mitophagy machinery to remove the damaged mitochondria before they can cause harm. The current study determined that mitochondrial injury, specifically depolarization, initiates mitophagy to prevent damaged mitochondria from accumulating in cells. Blocking depolarization after ethanol exposure also blocks mitophagy, preventing mitochondrial depletion. Flavonoids may slow lung function decline due to aging Johns Hopkins School of Public Health, May 22, 2022 Previous research has shown that the plant-produced chemicals known as flavonoids have beneficial antioxidant and anti-inflammatory properties. Anthocyanins, the type of flavonoid investigated in the current study, have been detected in lung tissue shortly after being ingested, and in animals models of chronic obstructive pulmonary disease (COPD). The plant chemicals appear to reduce mucus and inflammatory secretions. The researchers analyzed data from 463 adults (average age: 44) who participated in the second and third European Community Respiratory Health Surveys from 2002 to 2012. The researchers also analyzed the association between anthocyanin consumption and lung function in smokers, those who had never smoked and those who quit. The association between high consumption of the flavonoids and reduced lung function decline appeared to be stronger among both never smokers and those who had quit than in the general study population. Among smokers, the study did not find an association between anthocyanin intake and lung function. “Our study suggests that the general population could benefit from consuming more fruits rich in these flavonoids like berries, particularly those who have given up smoking or have never smoked, Dr. Larsen said. Medication doesn't help kids with ADHD learn, study finds Florida International University, May 24, 2022 For decades, most physicians, parents and teachers have believed that stimulant medications help children with attention deficit hyperactivity disorder (ADHD) learn. However, in the first study of its kind, researchers found medication has no detectable impact on how much children with ADHD learn in the classroom. Approximately 10% of children in the U.S. are diagnosed with ADHD and more than 90% of them are prescribed stimulant medication as the main form of treatment in school settingsbecause most physicians believe that medication will result in better academic achievement. Researchers evaluated 173 children between the ages of 7 and 12 with ADHD participating in the center's Summer Treatment Program, a comprehensive eight-week summer camp program for children with ADHD and related behavioral, emotional and learning challenges. Each child was randomized to be medicated with a sustained-release stimulant medication during either the first or second of the instructional phases, receiving a placebo during the other. Contrary to expectations, researchers found that children learned the same amount of science, social studies, and vocabulary content whether they were taking the medication or the placebo. Mediterranean diet may blunt air pollution's ill health effects NYU School of Medicine May 21, 2022 Eating a Mediterranean diet may protect people from some of the harm of long-term exposure to air pollution, and reduce their risk of dying from heart attacks, stroke and other causes of death, according to new research. The researchers analyzed data from the National Institutes of Health (NIH)-American Association of Retired Persons (AARP) Diet and Health Study. Over 17 years, the study followed 548,699 people (average age 62 at enrollment) from 6 states. During that time, 126,835 people in the study group died. The researchers created five groups of participants based on their level of adherence to a Mediterranean diet and linked participants to estimates of long-term exposure to fine particulate matter (PM2.5), nitrous oxide (NO2) and ozone (O3) based on census tract information. When comparing those least and most adherent to a Mediterranean diet, the study found that: Deaths from all causes increased by 5 percent for every 10 parts per billion (ppb) increase in long-term average NO2 exposure in those least adherent, compared to 2 percent among the most adherent. Cardiovascular disease deaths increased by 17 percent for every 10 micrograms per cubic meter (μg/m3) increase in long-term average PM2.5 exposure in those least adherent, compared to 5 percent among the most adherent. Cardiovascular disease deaths increased by 10 percent for every 10 ppb increase in NO2. exposure in those least adherent, compared to 2 percent among the most adherent. Heart attack deaths increased by 20 percent for every 10 μg/m3 increase in PM2.5 exposure in those least adherent, compared to 5 percent among the most adherent. Heart attack deaths increased by 12 percent for every single ppb increase in NO2 exposure in those least adherent, compared to 4 percent among the most adherent. Why blueberries are an effective weapon in the war against Alzheimer's disease University of Cincinnati, May 21, 2022 Could a plump, little blueberry really hold colossal promise in the fight against Alzheimer's disease? New research adds to the growing evidence that blueberries, bursting with antioxidants, could help diminish the devastating defects of dementia. Newly released study findings show that certain flavonoids found in blueberries could also hold the key to lessening the effects of Alzheimer's disease. The researchers, led by Krikorian, believe that blueberries' beneficial effects against Alzheimer's could be due to certain flavonoids found in the berries. Known as anthocyanins, they have been shown to improve cognition in tests with animals. Those receiving the blueberry powder were found to exhibit improved brain function and cognitive performance compared to those in the control group, with better memory and improved access to words and concepts. In another study, 94 people, aged 62 to 80, were divided into four groups. The subjects did not have diagnosed early-onset Alzheimer's, but did report feelings of having their memory decline.
Dr. Evan Noch interviews Dr. Joanna Phillips about her and her team manuscript entitled: "PI3K/AKT/mTOR signaling pathway activity in IDH-mutant diffuse glioma and clinical implications", published online in Neuro-Oncology in March 2022.
In which Neil Vasan, assistant professor of medicine and medical oncologist at the Columbia University Irving Medical Center, and Vaibhav discuss the biochemistry and structural biology of kinases, as well as their salience in cancer development and progression. Neil tells the story behind his critical discovery of hyper-activating double mutations cooccurring in cis on PI3K alleles, discusses his group's use of deep mutational scanning in elucidating mechanisms of drug resistance and disease pathogenesis, and describes his efforts to illuminate the dark phosphoproteome. As well, he discusses how proteomics complements genomic approaches to understanding cancer and provides advice for aspiring physician-scientists.
On this week's episode, Agustin shares his opinion on recent developments within the Covid landscape and the potential for a private vaccine market to emerge. Additionally, he shares his insights on $MEIP's recent misfortune and the FDA's growing reluctance to dole out accelerated approvals for PI3K inhibitors.Make sure to like, comment, subscribe and follow me on Twitter @biotech_bros
PI3K inhibitors have been an area of great interest for drug developers targeting cancers, but they've been difficult to turn into promising drugs due to safety concerns and a lack of efficacy in clinical trials. Pharming, though, believes PI3K can be a valuable target to treat APDS, a rare, immune condition. The company is working to develop Leniolisib, which it licensed from the drug giant Novartis in 2019. We spoke to Anurag Relan, chief medical officer of Pharming, about APDS, the role its PI3K inhibitors can play in treating the condition, and why these drugs may have broader use in autoimmune and inflammatory diseases.
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