Podcasts about Myc

Durant l'Antiquité, certains peuples ont dominé de vastes régions pendant des siècles, avant de connaître un brusque déclin. C'est notamment le cas des Hittites. Entre 1.650 et 1.200 avant notre ère, ils ont formé un Empire qui s'étendait sur une partie de l'Anatolie, dans la Turquie actuelle, et une part de la Syrie. Puis d'une manière assez soudaine, vers 1.200 avant J.-C., cette civilisation hittite, qui pouvait rivaliser avec l'Égypte de Ramsès II, s'est effondrée. La capitale, Hattusa, aujourd'hui classée au patrimoine mondial de l'Unesco, a été abandonnée par ses habitants et livrée aux flammes. Durant ce qu'il est convenu d'appeler l'"effondrement de l'âge du bronze", d'autres Empires, comme celui des Mycéniens par exemple, ont également périclité. Les historiens n'on pas manqué de s'interroger sur les raisons d'un pareil déclin. On a évoqué des invasions, perpétrées notamment par ceux que les Égyptiens appelaient les "peuples de la mer". On a aussi parlé d'épidémies meurtrières. Mais, même si ces faits ont dû avoir leur part dans la chute de l'Empire hittite, la vraie raison serait à rechercher dans un profond changement climatique. En effet, des chercheurs ont examiné des genévriers utilisés dans la construction de monuments funéraires. L'étude attentive des cernes de ces arbres et la présence de carbone, dans le bois, en apprennent beaucoup sur les conditions climatiques de l'époque. Cet examen a ainsi révélé le passage progressif, aux XIIIe et XIIe siècle avant J.-C., à un climat beaucoup plus sec. Les chercheurs ont même pu identifier trois années consécutives particulièrement arides, 1198, 1197 et 1196 avant notre ère. Tout laisse à penser que, durant ces trois années successives, les récoltes furent très mauvaises. Si, grâce aux réserves de blé amassées dans les greniers, il était possible de résister à une ou même deux années de pénurie, la troisième année de sécheresse a pu entraîner de véritables catastrophes. Des disettes, accompagnées de maladies, on pu se manifester dans l'Empire hittite, suscitant des émeutes et des troubles qui, d'après cette explication, ont fini par avoir raison de la puissance hittite. Learn more about your ad choices. Visit megaphone.fm/adchoices

Crossref is a non-profit organization that logs and updates citations for scientific publications. Each month, Crossref identifies a list of the most popular Oncotarget papers based on the number of times a DOI is successfully resolved. Below are Crossref's Top 10 Oncotarget DOIs in 2022. 10: Cell fusion as a link between the SARS-CoV-2 spike protein, COVID-19 complications, and vaccine side effects DOI: https://doi.org/10.18632/oncotarget.28088 Author: Yuri Lazebnik 9: A Jurkat 76 based triple parameter reporter system to evaluate TCR functions and adoptive T cell strategies DOI: https://doi.org/10.18632/oncotarget.24807 Authors: Sandra Rosskopf, Judith Leitner, Wolfgang Paster, Laura T. Morton, Renate S. Hagedoorn, Peter Steinberger, and Mirjam H.M. Heemskerk 8: IL-37 suppresses hepatocellular carcinoma growth by converting pSmad3 signaling from JNK/pSmad3L/c-Myc oncogenic signaling to pSmad3C/P21 tumor-suppressive signaling DOI: https://doi.org/10.18632/oncotarget.13196 Authors: Rui Liu, Chengyong Tang, Ai Shen, Huating Luo, Xufu Wei, Daofeng Zheng, Chao Sun, Zhongtang Li, Di Zhu, Tingting Li, and Zhongjun Wu 7: Apatinib-based targeted therapy against pulmonary sarcomatoid carcinoma: a case report and literature review DOI: https://doi.org/10.18632/oncotarget.25989 Authors: Xiaofeng Li, Yueming He, Jinfeng Zhu, Hongxia Pang, Yongwei Lin, and Jinyang Zheng 6: Treasures from trash in cancer research DOI: https://doi.org/10.18632/oncotarget.28308 Authors: Fabiano Cordeiro Moreira, Dionison Pereira Sarquis, Jorge Estefano Santana de Souza, Daniel de Souza Avelar, Taíssa Maria Thomaz Araújo, André Salim Khayat, Sidney Emanuel Batista dos Santos, and Paulo Pimentel de Assumpção 5: Real-world survival analysis by tumor mutational burden in non-small cell lung cancer: a multisite U.S. study DOI: https://doi.org/10.18632/oncotarget.28178 Authors: Connor Willis, Hillevi Bauer, Trang H. Au, Jyothi Menon, Sudhir Unni, Dao Tran, Zachary Rivers, Wallace Akerley, Matthew B. Schabath, Firas Badin, Ashley Sekhon, Malini Patel, Bing Xia, Beth Gustafson, John L. Villano, John-Michael Thomas, Solomon J. Lubinga, Michael A. Cantrell, Diana Brixner, and David Stenehjem 4: Continuous treatment with abemaciclib leads to sustained and efficient inhibition of breast cancer cell proliferation DOI: https://doi.org/10.18632/oncotarget.28249 Authors: Raquel Torres-Guzmán, Maria Patricia Ganado, Cecilia Mur, Carlos Marugan, Carmen Baquero, Yanzhu Yang, Yi Zeng, Huimin Bian, Jian Du, Alfonso de Dios, Oscar Puig, and María José Lallena 3: Increased gut permeability in cancer cachexia: mechanisms and clinical relevance DOI: https://doi.org/10.18632/oncotarget.24804 Authors: Laure B. Bindels, Audrey M. Neyrinck, Audrey Loumaye, Emilie Catry, Hannah Walgrave, Claire Cherbuy, Sophie Leclercq, Matthias Van Hul, Hubert Plovier, Barbara Pachikian, Luis G. Bermúdez-Humarán, Philippe Langella, Patrice D. Cani, Jean-Paul Thissen, and Nathalie M. Delzenne 2: Inflammatory responses and inflammation-associated diseases in organs DOI: https://doi.org/10.18632/oncotarget.23208 Authors: Linlin Chen, Huidan Deng, Hengmin Cui, Jing Fang, Zhicai Zuo, Junliang Deng, Yinglun Li, Xun Wang, and Ling Zhao 1: Proteomic profiling of skeletal and cardiac muscle in cancer cachexia: alterations in sarcomeric and mitochondrial protein expression DOI: https://doi.org/10.18632/oncotarget.25146 Authors: Angie M. Y. Shum, Anne Poljak, Nicholas L. Bentley, Nigel Turner, Timothy C. Tan, and Patsie Polly _______________________________ About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com

Videos: Brought to you by… Pfizer! FORMER PFIZER VP, DR. MIKE YEADON – EVERYTHING WE HAVE BEEN TOLD ABOUT COVID-19 WAS A LIE Fauci didn't want autopsies done on Covid victims. I wonder why? Dr. Peter McCullough SLAMS Pfizer board member over censorship and propaganda | Redacted News Study explores effects of dietary choline deficiency on neurologic and system-wide health Arizona State University, January 16, 2023 Choline, an essential nutrient produced in small amounts in the liver and found in foods including eggs, broccoli, beans, meat and poultry, is a vital ingredient for human health. A new study explores how a deficiency of dietary choline adversely affects the body and may be a missing piece in the puzzle of Alzheimer's disease. It's estimated that more than 90% of Americans are not meeting the recommended daily intake of choline. The current research, conducted in mice, suggests that dietary choline deficiency can have profound negative effects on the heart, liver and other organs. Lack of adequate choline is also linked with profound changes in the brain associated with Alzheimer's disease. These include pathologies implicated in the development of two classic hallmarks of the illness: amyloid plaques, which aggregate in the intercellular spaces between neurons; and tau tangles, which condense within the bodies of neurons. The new research, led by scientists at Arizona State University and published in Aging Cell, describes pathologies in normal mice deprived of dietary choline and in choline-deficient transgenic mice, the latter of which already exhibit symptoms associated with the disease. In both cases, dietary choline deficiency results in liver damage, enlargement of the heart and neurologic alterations in the AD mice, typically accompanying Alzheimer's disease and including increased levels of plaque-forming amyloid-beta protein and disease-linked alterations in tau protein. Further, the study illustrates that choline deficiency in mice causes significant weight gain, alterations in glucose metabolism (which are tied to conditions such as diabetes), and deficits in motor skills. In the case of humans, “it's a twofold problem,” according to Ramon Velazquez, senior author of the study and assistant professor with the ASU-Banner Neurodegenerative Disease Research Center. “First, people don't reach the adequate daily intake of choline established by the Institute of Medicine in 1998. And secondly, there is vast literature showing that the recommended daily intake amounts are not optimal for brain-related functions.” The research highlights a constellation of physical and neurological changes linked to choline deficiency. Sufficient choline in the diet reduces levels of the amino acid homocysteine, which has been recognized as a neurotoxin contributing to neurodegeneration, and is important for mediating functions such as learning and memory through the production of acetylcholine. The growing awareness of choline's importance should encourage all adults to ensure proper choline intake. This is particularly true for those on plant-based diets, which may be low in naturally occurring choline, given that many foods high in choline are eggs, meats, and poultry. Plant-based, choline-rich foods, including soybeans, Brussels sprouts and certain nuts can help boost choline in these cases. Moreover, inexpensive, over-the-counter choline supplements are encouraged to promote overall health and guard the brain from the effects of neurodegeneration. The new study examines mice at 3-12 months, or early to late adulthood (roughly equivalent to 20-60 years of age for humans). In the case of both normal and transgenic mice displaying symptoms of Alzheimer's, those exposed to a choline-deficient diet exhibited weight gain and adverse effects to their metabolism. Damage to the liver was observed through tissue analysis, as was enlargement of the heart. Elevated soluble, oligomeric and insoluble amyloid-beta protein were detected, as well as modifications to tau protein characteristic of those leading to neurofibrillary tangles in the brain. Further, choline-deficient mice performed poorly in a test of motor skills, when compared with mice receiving adequate choline in their diet. These adverse effects were heightened in the transgenic mice. Translating these findings to humans, this implies that people who are predisposed to Alzheimer's disease or in the throes of the illness should ensure they are getting enough choline.”Our work provides further support that dietary choline should be consumed on a daily basis given the need throughout the body,” Velazquez says. (NEXT) Melanoma: Vitamin D supplements linked to reduced skin cancer risk University of Eastern Finland & Kuopio University, January 15, 2023 A new study finds that the regular use of vitamin D is associated with lower rates of melanoma skin cancer. The cross-sectional study was a collaboration between the University of Eastern Finland and Kuopio University Hospital. The research involved 498 Finnish adults determined by dermatologists to be at high risk of skin cancer, such as melanoma, as well as squamous cell carcinoma and basal cell carcinoma. According to researchers, people who took vitamin D regularly were less likely to have had melanoma in the past or currently and were deemed by dermatologists to be less likely to develop melanoma in the future. Study participants ranged in age from 21 to 79 years old, including 253 males and 245 females. Participants were divided into three groups based on their intake of vitamin D supplements: non-use, occasional use, or regular use. The researchers were also interested in finding out whether regular use of vitamin D supplements corresponded to higher blood levels of vitamin D, known as serum calcidiol or 25-hydroxy-vitamin D3. This is the “storage form” of vitamin D in the body. Some research has linked low serum calcidiol with increased cancer risk, while other research has suggested otherwise. Nonetheless, it is a measure often used to determine a person's vitamin D levels. After testing serum calcidiol levels in 260 participants, researchers found that regular vitamin D supplementation corresponded with the highest levels of serum calcidiol and non-supplementation with the lowest levels. “Human skin itself expresses [the enzyme] CYP27A1 that produces calcidiol from vitamin D, and CYP27B1 that produces biologically very active calcitriol from calcidiol,” Dr. Harvima explained, noting that enzyme expression determines the level of vitamin D and its metabolites in the body. (NEXT) New research furthers case for exercise promoting youthfulness University of Arkansas, January 17, 2023 A recent paper published in the Journal of Physiology deepened the case for the youthfulness-promoting effects of exercise on aging organisms, building on previous work done with lab mice nearing the end of their natural lifespan that had access to a weighted exercise wheel. For this paper, the researchers compared aging mice that had access to a weighted exercise wheel with mice that had undergone epigenetic reprogramming via the expression of Yamanaka factors. The Yamanaka factors are four protein transcription factors (identified as Oct3/4, Sox2, Klf4 and c-Myc, often abbreviated to OKSM) that can revert highly specified cells (such as a skin cell) back to a stem cell, which is a younger and more adaptable state. The Nobel Prize in Physiology or Medicine was awarded to Dr. Shinya Yamanaka for this discovery in 2012. In the correct dosages, inducing the Yamanaka factors throughout the body in rodents can ameliorate the hallmarks of aging by mimicking the adaptability that is common to more youthful cells. Of the four factors, Myc is induced by exercising skeletal muscle. Myc may serve as a naturally induced reprogramming stimulus in muscle, making it a useful point of comparison between cells that have been reprogrammed via over expression of the Yamanaka factors and cells that have been reprogrammed through exercise—”reprogramming” in the latter case reflecting how an environmental stimulus can alter the accessibility and expression of genes. Ultimately, the team determined that exercise promotes a molecular profile consistent with epigenetic partial programming. That is to say, exercise can mimic aspects of the molecular profile of muscles that have been exposed to Yamanaka factors (thus displaying molecular characteristics of more youthful cells). This beneficial effect of exercise may in part be attributed to the specific actions of Myc in muscle. Murach sees their research as further validation of exercise as a polypill. “Exercise is the most powerful drug we have,” he says, and should be considered a health-enhancing—and potentially life-extending—treatment along with medications and a healthy diet. (NEXT) Exploiting the synergy of nutraceuticals for cancer prevention and treatment Research suggests that free radicals (ROS) generated upon mixing two nutraceuticals—resveratrol and copper—can help ameliorate various diseases by inactivating cell-free chromatin particles Tata Memorial Centre (India), January 16, 2023 Chromatin comprises a complex mixture of DNA and proteins that forms the structural basis of chromosomes in the cellular nuclei. When cells die, they release cell-free chromatin particles or “cfChPs” into the circulatory system. In 1996, evidence for tumour-derived DNA circulating in the blood of cancer patients was first reported. This evidence caught the interest Dr. Indraneel Mittra, who is now Professor Emeritus and the Dr. Ernest Borges Chair in Translational Research at Tata Memorial Centre in Mumbai, India. His tryst with research on genetic material in cancer metastases began, and after 15 years of research he has presented various papers, developing a body of evidence that indicates the critical role of cfChPs in orchestrating development of not only cancer, but various other diseases. Emerging evidence indicates that cfChPs play an essential role in ageing, sepsis, cancer development, and chemotherapy-related toxicity. With respect to the latter, Prof. Mittra explains, “Chemo-toxicity is not primarily caused by chemotherapeutic drugs, but rather by cfChPs that are released from the first cells that die after chemotherapy. The released cfChPs set in motion a cascading effect, increasingly damaging the DNA of healthy host cells, and triggering inflammatory processes in a vicious cycle that perpetuates and prolongs the toxicity of chemotherapy.” Recently, a team from Tata Memorial Centre have demonstrated the therapeutic benefits of a pro-oxidant mixture of resveratrol and copper, R-Cu, in patients undergoing chemotherapy for advanced gastric cancer. Combining R with Cu (R-Cu) leads to the generation of free oxygen radicals which can inactivate the offending cfChPs. In this context, the research team launched a single-arm phase II clinical trial to study the synergistic effects of R-Cu administration on cfChPs inactivation in patients with advanced gastric cancer. The primary objective was to determine whether R-Cu, via cfChPs' inactivation, was successful in reducing the grade ≥ 3 toxicity seen with docetaxel-based chemotherapies. To this end, the researchers monitored the likely changes in the toxicities of chemotherapeutic treatments using a grading system that provides a framework for the assessment of unwanted physiological effects. The results were promising—although R-Cu did not reduce haematological toxicities, it significantly reduced the incidence of non-haematological toxicities comprising hand-foot syndrome, diarrhoea, and vomiting. Moreover, R-Cu reduced docetaxel exposure compared to the control arm without affecting efficacy in terms of overall survival. (NEXT) Deep meditation may alter gut microbes for better health Shanghai Jiao Tong University School of Medicine (China), January 16, 2023 Regular deep meditation, practiced for several years, may help to regulate the gut microbiome and potentially lower the risks of physical and mental ill health, finds a small comparative study published in the open access journal General Psychiatry. The gut microbes found in a group of Tibetan Buddhist monks differed substantially from those of their secular neighbors, and have been linked to a lower risk of anxiety, depression, and cardiovascular disease. Research shows that the gut microbiome can affect mood and behavior through the gut–brain axis. This includes the body's immune response, hormonal signaling, stress response and the vagus nerve—the main component of the parasympathetic nervous system, which oversees an array of crucial bodily functions. The significance of the group and specimen design is that these deep-thinking Tibetan monks can serve as representatives of some deeper meditations. Although the number of samples is small, they are rare because of their geographical location. The researchers analyzed the stool and blood samples of 37 Tibetan Buddhist monks from three temples and 19 secular residents in the neighboring areas. None of the participants had used agents that can alter the volume and diversity of gut microbes: antibiotics; probiotics; prebiotics; or antifungal drugs in the preceding 3 months. Sample analysis revealed significant differences in the diversity and volume of microbes between the monks and their neighbors.”Collectively, several bacteria enriched in the meditation group [have been] associated with the alleviation of mental illness, suggesting that meditation can influence certain bacteria that may have a role in mental health,” write the researchers. These include Prevotella, Bacteroidetes, Megamonas and Faecalibacterium species, the previously published research suggests. Finally, blood sample analysis showed that levels of agents associated with a heightened risk of cardiovascular disease, including total cholesterol and apolipoprotein B, were significantly lower in the monks than in their secular neighbors by their functional analysis with the gut microbes. (NEXT) Curcumin/Boswellia shows promise in chronic kidney disease Baylor University, January 14, 2023. The Journal of Complementary and Integrative Medicine reports the finding of researchers at Baylor University of a reduction in a marker of inflammation among chronic kidney disease patients given a combination of Curcuma longa (curcumin) and Boswellia serrata. The study included sixteen individuals receiving standard care for chronic kidney disease who were not undergoing dialysis. Participants were randomized to receive capsules containing curcumin from turmeric extract plus Boswellia serrata, or a placebo for eight weeks. Blood samples collected before and after treatment were analyzed for plasma interleukin-6 (IL-6), tumor necrosis factor alpha (markers of inflammation), and the endogenous antioxidant enzyme glutathione peroxidase, as well as serum C-reactive protein (CRP, another marker of inflammation.) Blood test results from the beginning of the study revealed increased inflammation and reduced glutathione peroxide levels. At the study's conclusion, participants who received curcumin and Boswellia serrata experienced a reduction in interleukin-6 in comparison with pretreatment values, indicating decreased inflammation, while IL-6 values rose among those who received a placebo. In their discussion of the findings, the authors remark that curcumin and Boswellia serrata have been separately shown to lower interleukin-6 via inhibition of the nuclear factor kappa beta and mitogen activated protein kinase (MAPK) signaling pathways.

Penúltimo capítulo de temporada y en el episodio de hoy toca el turno de platicar del West Highland White Terrier y para ello tendremos de invitado a Bernardo Navia, criador profesional y fundador de Criadero Navia “La Casa del West Highland”. En el ¿sabías qué? de la semana hablaremos del abandono de perros de trabajo por parte del ejército de los Estados Unidos.  Y para finalizar, tendremos nuestra gustada sección, a Otro Perro con ese Hueso, con la intervención del MVZ Everardo Salas, quién resolverá algunos de los mitos más populares del mundo de los canes.   CriaderoNavia https://www.facebook.com/Criadero-West-Highland-Mexico-1766695543560929  Petco https://www.facebook.com/Petco.Mexico   M&CAdiestramientoCanino https://www.facebook.com/MyC.Adiestramiento.Canino   Bicu Pet Fashion https://www.facebook.com/BicuPetFashion   Husse https://www.facebook.com/hussepueblatlaxcala   UMAD https://www.facebook.com/universidadmaderopuebla  Croquetones Go https://www.facebook.com/Croquetonespuebla

Toca el turno de conocer a detalle una de las razas que ganó fama gracias a su aparición en la película animada de 1955  de Disney, La Dama y el Vagabundo, así es, nos referimos al Cocker Spaniel Americano, y para ello tendremos la intervención  de Saúl Alberto Ruíz Gómez, criador profesional y fundador de Gos D´orella Kennel, quien nos hablará de esta elegante raza.  En el sabías que de la semana, revelaremos un dato que posiblemente desconocías y que podría evitarte pasar un mal momento con tu mascota.   Para finalizar tendremos nuestra polémica sección “El Perrometro” donde debatiremos los pros y contras del corte de orejas en los perros, un tema que mucha controversia suele generar.  Gos D´orella Kennel https://www.facebook.com/rgomez.saul Petco https://www.facebook.com/Petco.Mexico M&CAdiestramientoCanino https://www.facebook.com/MyC.Adiestramiento.Canino Bicu Pet Fashion https://www.facebook.com/BicuPetFashion Husse https://www.facebook.com/hussepueblatlaxcala UMAD https://www.facebook.com/universidadmaderopuebla Velazquez Kennel https://www.facebook.com/velazquezkennelbti CriaderoNavia https://www.facebook.com/Criadero-West-Highland-Mexico-1766695543560929

A new research paper was published in Oncotarget's Volume 13 on December 6, 2022, entitled, “Expression of p-STAT3 and c-Myc correlates with P2-HNF4α expression in nonalcoholic fatty liver disease (NAFLD).” Nonalcoholic fatty liver disease (NAFLD) is associated with the metabolic syndrome and is rapidly becoming one of the major causes of hepatic cirrhosis and hepatocellular carcinoma (HCC), although some cases of HCC have developed in non-cirrhotic livers [1–8]. Although the percentage of patients with NAFLD who ultimately progress to fibrosis and later to HCC is relatively small, the number is significant because of the sheer number of patients who have NAFLD. Because there are no reliable biomarkers to predict the risk of HCC in patients with NAFLD, designing effective and cost-effective surveillance programs aimed at prevention and early detection of HCC is difficult, if not impossible. Therefore, there is an urgent need to identify such biomarkers and especially those that may appear at different stages of progression toward HCC. In the current study, researchers Mamoun Younes, Lin Zhang, Baharan Fekry, and Kristin Eckel-Mahan from George Washington University School of Medicine and Health Sciences and McGovern Medical School at the University of Texas Health Science Center (UTHealth) studied the expression of two hepatocyte nuclear factor 4 alpha (HNF4α) isoforms, p-STAT3. and c-Myc in 49 consecutive liver biopsies with nonalcoholic fatty liver disease (NAFLD) using immunohistochemistry. “The aim of this study was to determine the relationships between p-STAT3, c-Myc and P2-HNF4α expression in biopsies from livers with NAFLD as potential biomarkers of HCC risk.” All 49 biopsies (100%) were positive for nuclear expression of P1-HNF4α. Twenty-eight (57%) cases were positive for P2-HNF4α, 6 (12%) were positive for p-STAT3 and 5 (10%) were positive for c-Myc. All 6 (100%) p-STAT3-positive cases were also positive for P2-HNF4α (p = 0.03). p-STAT3-positive cases were more likely to be positive for c-Myc (67% vs. 2%, p = 0.0003). Four cases were positive for P2-HNF4α, p-STAT3 and c-Myc. p-STAT3 expression was associated with hypertension (p = 0.037). All c-Myc positive biopsies were from patients with obesity, diabetes and hypertension. Only c-Myc expression was associated with advanced fibrosis; three (60%) of the c-Myc positive cases were associated with advanced fibrosis in contrast to 7 (10%) of the 44 c-Myc negative cases (p = 0.011). “Based on these results, we hypothesize with the following sequence of events with progression of NAFLD: P2-HNF4α expression is followed by expression of p-STAT3 which in turn is followed by the expression of c-Myc. Additional larger studies are needed to confirm these findings.” DOI: https://doi.org/10.18632/oncotarget.28324 Correspondence to: Mamoun Younes - myounes@mfa.gwu.edu Video: https://www.youtube.com/watch?v=LVR29K6P5I4 Keywords: hepatocyte nuclear factor four alpha, steatohepatitis, immunohistochemistry, hepatocellular carcinoma, isoform 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

En el episodio de hoy tendremos un invitado de talla internacional y haremos un enlace hasta la madre patria para platicar con el Sr. Carlos Jose Sanchez Beldad, Expositor, Criador Profesional y Fundador de Bouleonuba Kennel, con quien tendremos quien nos contará todo acerca del Bulldog Francés. En el ¿sabías qué? de la semana, conoceremos todos los detalles de la nueva mascota oficial de la selección española de fútbol. Y para finalizar tendremos la sección “A otro perro con ese hueso, con la intervención del MVZ Everardo Salas de Medi-Vets Centro Médico Veterinario, quien aclarará algunos de los mitos más comunes del mundo canino. Carlos Jose Sanchez Beldad (Bouleonuba Kennel) https://www.facebook.com/BOULEONUBA Petco https://www.facebook.com/Petco.Mexico M&CAdiestramientoCanino https://www.facebook.com/MyC.Adiestramiento.Canino Bicu Pet Fashion https://www.facebook.com/BicuPetFashion Husse https://www.facebook.com/hussepueblatlaxcala UMAD https://www.facebook.com/universidadmaderopuebla Torettos Burdeos https://www.facebook.com/ricardo.perezabreu Ravell Kennel https://www.facebook.com/RavellKennelMerida

Se vive la pasión mundialista y en el episodio de hoy  hablaremos de un perro originario de tierras pamperas ¡así es! toca el turno de conocer más a fondo al Dogo Argentino ¡El Messi de los perros! Para ello, contaremos con la intervención de Gerardo Reyes, expositor, criador profesional y fundador de Dogos Reyes. En el ¿Sabías qué? de la semana rendiremos un pequeño homenaje a Frida, la perra rescatista que se ganó el corazón de todos los mexicanos. Conoceremos algunos datos que poco se sabían de ella.  Para finalizar, tendremos nuestra tan controversial sección “El Perrometro” donde debatiremos los pros y contras de dormir con el perro.   Dogos Reyes https://www.facebook.com/profile.php?id=100082241036638  Petco https://www.facebook.com/Petco.Mexico  M&CAdiestramientoCanino https://www.facebook.com/MyC.Adiestramiento.Canino  Bicu Pet Fashion https://www.facebook.com/BicuPetFashion  Husse https://www.facebook.com/hussepueblatlaxcala  UMAD https://www.facebook.com/universidadmaderopuebla  Sutams Kennel https://www.facebook.com/sutamskennel  Rotts Vom Cervantes https://www.facebook.com/profile.php?id=100010648780156

On this episode of the Dr. Tyna Show, I am going solo and I am going to be talking with you today all about Naturopathic prospectives on sauna and hydrotherapy and why I think protocols are bullish*t.Topics Covered In This Episode:Benefits of sauna therapyWhen to use a saunaWho can benefit from sauna therapyBy blanket sauna protocols are not appropriateMy personal sauna protocolWhen I use a saunaWhen I don't use a saunaSeasonal effective disorderSauna and depressionThis episode is sponsored by Sunlighten Saunas. You can save up to $600 when you purchase through THIS LINK and let them know Dr. Tyna sent you!Affiliate Link for Savings (can also be found on my website at drtyna.com): https://sunlighten.com/?utm_source=DrTyna&utm_medium=Partner&leadsource=DrTyna&utm_campaign=DrTynaFurther Listening:EP 19: My C-19 Experience - Solo EpisodeEP 24: 10 Reasons I Love My Sauna - Solo EpisodeEP 68: Hot and Healthy with Connie Zack of Sunlighten Saunas Get full access to Dr. Tyna Show Podcast & Censorship-Free Blog at drtyna.substack.com/subscribe

En el episodio de hoy toca el turno de hablar del Rottweiler, para ello contaremos con la intervención de Enrique González, Juez Especialista de la raza, Criador y expositor profesional, además de ser Fundador de Criadero Von Der Gopa´s Rottweilers, quien nos platica más acerca de esta popular raza. En el sabías que de la semana conoceremos de la capacidad auditiva súper desarrollada que tienen los perros, cuatro veces superior al ser humano. Y en nuestra sección “La perra duda” tendremos de invitado al MVZ Iván Flores de Bicu Pet Fashion quien estará resolviendo algunas de las preguntas que el público nos hace llegar. Criadero Von Der Gopa´s https://vondergopas.com/ Petco https://www.facebook.com/Petco.Mexico M&CAdiestramientoCanino https://www.facebook.com/MyC.Adiestramiento.Canino Bicu Pet Fashion https://www.facebook.com/BicuPetFashion Husse https://www.facebook.com/hussepueblatlaxcala UMAD https://www.facebook.com/universidadmaderopuebla Garces Store Malinois https://www.facebook.com/garcesstore1989 Rotts Mejía https://www.facebook.com/profile.php?id=100018961052374

Omomyc es el nombre provisional de un nuevo fármaco desarrollado en Barcelona, España, por parte de un equipo de investigación que lleva trabajando 25 años en algo que se consideraba biológica y farmacológicamente imposible, al menos hasta la fecha, penetrar en un tipo de proteína, denominada MYC, que se encuentra en el núcleo de las células y que es responsable de la regeneración celular necesaria para la vida, pero también de la proliferación dañina asociada a la enfermedad del cáncer. Tras conseguir demostrar progresos muy importantes en laboratorio y con animales, OMOMYC ha comenzado sus pruebas con humanos y ha superado la fase 1, la menos numerosa, con éxito. En este momento se disponen a comenzar los ensayos con humanos (más numerosa y con pacientes en mejor perspectiva) de fase 2, o lo que es lo mismo, de las 5 fases necesarias para que un medicamento pueda llegar al mercado, Omomyc está a punto de arrancar su cuarto estadio. Si las fases 2 y 3 con humanos llegan a buen puerto el tratamiento contra el cáncer podría tener una nueva y poderosa arma que hasta ahora se había considerado inviable. En este podcast te contamos todos los detalles e información de un fármaco que puede salvar miles de vida y mejorar también la de las personas que parecen la enfermedad del cáncer. Mis Aparatos y equipos imprescindibles para trabajar y vivir: https://www.amazon.es/shop/juanfranciscocalero-clubonmotor Apóyame para hacer más y mejores vídeos en PATREON. Sé mi mentor: https://www.patreon.com/jfcalero Sígueme en INSTAGRAM, TWITTER o AMBAS, súperfácil: @jfcalero No te vayas a la cama sin saber algo más, o al menos sin saber algo nuevo. Si lo hiciste, misión cumplida, gracias por acompañarme. Puedes ver el video correspondiente a este podcast en el siguiente enlace: https://www.youtube.com/watch?v=SFpYc6WfjU4

En el programa de hoy hablaremos acerca de los mitos y realidades sobre la Estética Canina y para ello contaremos con la intervención del Groomer profesional y fundador de Peludogs & Vet, David Padilla, quien nos acompañará para platicar de este fascinante tema. En el sabías qué de la semana te contaremos de la importancia que ha tenido el Xoloitzcuintle en nuestra cultura desde épocas prehispánicas. Y en la sección “El perrometro” tendremos un acalorado debate acerca de los pros y los contras de viajar con tu mascota. Somos Los RecomendaDogs…Porque amamos a los perros. David Padilla (Peludogs & Vet) https://www.facebook.com/Peludogsapi Petco https://www.facebook.com/Petco.Mexico M&CAdiestramientoCanino https://www.facebook.com/MyC.Adiestramiento.Canino Bicu Pet Fashion https://www.facebook.com/BicuPetFashion Husse https://www.facebook.com/hussepueblatlaxcala UMAD https://www.facebook.com/universidadmaderopuebla Criadero Von Der Gopa´s https://vondergopas.com/

En este tercer episodio conoceremos un poco más de una de las razas más populares entre las familias, en la industria del cine y por supuesto del mundo canófilo. ¡Así es! toca el turno de hablar del Pastor Alemán y para ello contaremos con la intervención de Gerardo Venegas, Criador Profesional y Fundador de Casa Von Vesa. En el ¿Sabías qué? platicaremos del curioso fenómeno que ocurre con los cachorros Dálmatas, los cuales nacen sin sus características manchas negras.  Para finalizar tendremos nuestra gustada sección “A otro perro con ese hueso” con la participación del MVZ Everardo Salas de Medi-Vets Centro Médico Veterinario.  M&CAdiestramientoCanino https://www.facebook.com/MyC.Adiestramiento.Canino  Petco https://www.facebook.com/Petco.Mexico  Bicu Pet Fashion  https://www.facebook.com/BicuPetFashion  Husse  https://www.facebook.com/hussepueblatlaxcala  UMAD  https://www.facebook.com/universidadmaderopuebla  Vom Haus Mejía  https://www.facebook.com/MejiaRotts.MiniBullterries Golden Dogs  https://www.facebook.com/goldendogsmex

En el episodio de hoy estaremos hablando de la educación canina ¿Qué hacer y que no hace con nuestros perro? y para ello, contaremos con la participación de Lupita Pérez y Jared Romero, adiestradores profesionales y fundadores de “M&C Adiestramiento Canino, En el ¿sabías que? de la semana, te contaremos del único país del mundo que ha sido capaz de  erradicar  la problemática de los perros en situación de calle. Y para finalizar tendremos nuestra sección “La Perra Duda” con  la intervención del MVZ Iván Flores de Bicu Pet Fashion. M&C Adiestramiento Canino https://www.facebook.com/MyC.Adiestramiento.Canino Petco https://www.facebook.com/Petco.Mexico Bicu Pet Fashion https://www.facebook.com/BicuPetFashion Husse https://www.facebook.com/hussepueblatlaxcala UMAD https://www.facebook.com/universidadmaderopuebla Vom Haus Gamez Rotts https://www.facebook.com/profile.php?id=100063556869501 LK-9 Services México https://www.facebook.com/LK9services

Estrenamos temporada y para celebrarlo, hoy tendremos un programa lleno de información. En Casta de Campeones hablaremos de una de las razas más polémicas, ¡Así es! toca el turno de conocer al Pastor Belga Malinois, y contaremos con la participación del Mtro. David Garcés Islas, Criador Profesional y Fundador de Garcés Store Malinois. En el sabías que de la semana, te platicaremos de una raza que ha sido reconocida como patrimonio nacional de Turkmenistán.  Para cerrar tendremos nuestra El Perrometro, donde debatiremos  si los tatuajes de identificación en los perros siguen siendo un método útil u obsoleto.  Garcés Store Malinois https://www.facebook.com/garcesstore1989  Petco https://www.facebook.com/Petco.Mexico  Bicu Pet Fashion https://www.facebook.com/BicuPetFashion  Husse https://www.facebook.com/hussepueblatlaxcala  M&C Adiestramiento Canino https://www.facebook.com/MyC.Adiestramiento.Canino  UMAD https://www.facebook.com/universidadmaderopuebla

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.22.508987v1?rss=1 Authors: Tiwari, S., Singh, A., Gupta, P., K, A., SINGH, S. Abstract: Mitochondrial homeostasis regulates energy metabolism, calcium buffering, cell function and apoptosis. The present study has been conducted to investigate the implications of ubiquitin-encoding gene UBA52 in mitochondrial physiology. Transient expression of Myc-UBA52 in neurons significantly inhibited the rotenone-induced increase in reactive oxygen species generation, nitrite level and depleted glutathione level. Mass spectrometric and co-immunoprecipitation data suggested the profound interaction of UBA52 with mitochondrial outer membrane channel protein, VDAC1 in both the wild-type and Myc-alpha-synuclein overexpressed neuronal cells and in the Parkinson disease (PD)-specific substantia nigra and striatal region of the rat brain. In vitro ubiquitylation assay revealed that UBA52 participates in the ubiquitylation of VDAC1 through E3 ligase CHIP. Myc-UBA52 overexpression in neurons further improved the mitochondrial functionality and cell viability by preventing the alteration in mitochondrial membrane potential, mitochondrial complex-I activity, translocation of cytochrome-c and p-Nrf2 along with effect on intracellular calcium uptake, thus collectively inhibiting the opening of mitochondrial permeability transition pore. Additionally, Myc-UBA52 expression in neuronal cells offered protection against apoptotic and autophagic cell death. Altogether, our findings delineate functional association between UBA52 and mitochondrial homeostasis, providing new insights into the deterrence of dopaminergic cell death during acute PD pathogenesis. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

C'est la fin de la guerre de Troie. Les rois grecs vainqueurs se séparent et chacun rentre chez soi, avec son armée. Avant de monter dans son navire, Agamemnon sacrifie aux Dieux. Ainsi, il fera bon voyage jusqu'à Mycènes, la cité dont il est le roi... Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. In the Research Round Up series, ASCO experts and members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, our guests will discuss new research in lung cancer, lymphoma, and childhood cancer that was presented at the 2022 ASCO Annual Meeting, held June 3-7 in Chicago, Illinois. First, Dr. Charu Aggarwal will discuss 3 studies looking at treatment options for people with non-small cell lung cancer. Dr. Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine in Philadelphia, Pennsylvania. She is also the Cancer.Net Associate Editor for Lung Cancer. You can view Dr. Aggarwal's disclosures at Cancer.Net. Dr. Aggarwal: Hello and welcome to this Cancer.Net podcast. I'm bringing you updates from the Annual Meeting of the American Society of Clinical Oncology, held in Chicago in 2022. I'm Dr. Charu Aggarwal. I'm the Leslye Heisler Associate Professor for Lung Cancer Excellence at the University of Pennsylvania's Abramson Cancer Center. I will be discussing updates on 3 studies today that offer insights and new advances in the management of patients with non-small cell lung cancer. I don't have any direct relationship with any of these companies or studies, and you can view a list of my disclosures on the Cancer.Net website. First off, I would like to talk a little bit about advances in the management of patients with EGFR exon 20 mutations. We know that a lot of advances have been made in the management of patients with non-small cell lung cancer, and much of that has been attributed to the fact that we are now able to deliver targeted therapy for a subset of patients. EGFR mutations form one such subset where we have a lot of oral drugs that are available, and we can offer these that improve survival, and patients can avoid chemotherapy, immunotherapy, and other IV infusional therapies. Within the subset of EGFR mutations lies this unique subset of EGFR exon 20 insertion mutations, which have been historically harder to target with currently available EGFR inhibitors. And over the last 5 years, we have seen tremendous growth of opportunities, targets, and new drugs for this subset of patients. The mutations in this subset forms about 2% to 5% of all non-small cell lung cancers. But now we have 2 FDA-approved drugs in this space, one being intravenously administered, amivantamab, and another that is orally available, mobocertinib. We covered this in a podcast as well as a blog, so please check those out on our Cancer.Net website. But building upon that progress, there is now another drug that was reported at ASCO. This drug is called CLN-081. And we saw preliminary activity in a phase 1 and 2 study of this molecule or this drug in patients with EGFR exon 20 insertion mutations. It's an orally available drug. The top line data is that it is safe, it is effective, it was tested in different doses. It was tested at less than 65 milligrams, 100 milligrams, and 150 milligrams, again, as I mentioned, administered orally, and we saw responses and patients that had previously received other therapies and may have progressed on other therapies. And what we found was that this drug also tends to have activity against brain metastases, which I think is this huge unmet need in the management of such patients. So I think more to come, but again, I think offers us an insight into what may be in the future, an attractive drug for our patients with EGFR exon 20 insertion mutations. So stay tuned, more on that in the future. Shifting gears, I would like to now talk about one of the common mutations. So we talked about EGFR exon 20, which is about only 2% to 5%, but the largest subset of mutations in non-small cell lung cancer really revolves around KRAS mutations, and these form about 30% to 35% of all mutations in non-squamous, non-small cell lung cancer. And amongst this group there is another subset which is KRAS G12C non-small cell lung cancer, that forms about 13% of all lung cancers. We have 1 approved drug already in this space by the name of sotorasib that is FDA approved for the management of patients with this particular mutation after having received 1 prior therapy, be it chemo-immunotherapy or immunotherapy. At this year's ASCO meeting, we heard data from a study called KRYSTAL-1, which looked at the activity and safety of another molecule called adagrasib, which is an orally available drug targeting KRAS G12C, again, in a similar population of patients with advanced and metastatic non-small cell lung cancer harboring a mutation. We found that this drug is again effective, the overall response rate was about 43%, the majority of the patients had stabilization of disease, about 80%, and many patients were able to remain on treatment with stabilization of disease. We found that this drug does have side effects and adverse events and most commonly of this were diarrhea, nausea, vomiting, and fatigue. Many patients did require dose reductions, but the activity of the drug remained despite dose reductions. Now, what would be the advantage of this drug against the currently available sotorasib? In another smaller study reported at ASCO, there seemed to be activity in the brain, including intracranial penetration with the use of this molecule, adagrasib, which has not been demonstrated before with other KRAS G12C inhibitors, so I think that makes it a potentially attractive option. Again, I will say that the report of this intracranial activity was in a very small subgroup of patients, so I think needs to be further corroborated in a larger study. Shifting gears again and talking about our last study, so I would like to highlight what do we do if, in case, patients don't have a targetable mutation. I want to highlight that we do have a lot of available options, and we are continuing to improve upon available options. The way we treat such patients is by using immunotherapy, either alone or in combination with chemotherapy. But what do we do after this treatment stops working? Researchers from the Southwestern Oncology Group, or SWOG, launched a massive national effort called Lung-MAP, which is basically a clinical trial that evaluates several different strategies all at once, either for patients with targetable mutations or for patients without a targetable alteration. And they reported results from a study that evaluated the combination of pembrolizumab with ramucirumab in patients that may have progressed after frontline immunotherapy. Now, pembrolizumab is immunotherapy, so the concept was, can we continue immunotherapy beyond progression and perhaps get some synergistic activity by using ramucirumab, which is a drug that prevents blood vessels from forming in the tumor itself. It's an anti-angiogenic agent, meaning that it is a targeted molecule that prevents blood vessel formation and promotes tumor death. What they found was that patients that received pembrolizumab and ramucirumab were more likely to live longer, so overall survival was longer for patients with this combination compared to a physician investigator discretion choice, such as chemotherapy in combination with ramucirumab or other chemotherapies that are otherwise used in the second line setting. And interestingly, we did not find a significant improvement in shrinkage with this combination of pembrolizumab and ramucirumab or a significant reduction in the time of progression-- or, sorry, prolongation of the time of progression of disease. But the overall survival findings are interesting, and I think that's why we are including them in this podcast because that's one of the approaches that is leading to an improvement in survival and improvement in outcomes. I will point out that this is a phase 2 study. These results would need to be validated in a large prospective phase 3 trial so that we can account for certain confounding factors that may have led to these results. Having said that, I think there's a tremendous excitement, there's tremendous excitement in this field. I gave you examples of, or highlighted, 3 studies: one in patients with EGFR exon 20 insertion mutations, another in KRAS G12C mutations, and the third in patients who may have already received either immunotherapy or chemoimmunotherapy. We will continue to update our Cancer.Net website with updates as they come through, new advances, new studies, so thanks for following, thanks for listening, and more to come. Stay tuned. Thank you. ASCO: Thank you, Dr. Aggarwal. Next, Dr. Christopher Flowers will discuss new research in treating people with different subtypes of lymphoma, including mantle cell lymphoma and diffuse large B-cell lymphoma. Dr. Flowers is the Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and was appointed Division Head ad interim of Cancer Medicine in August 2020. He is also the 2022 Cancer.Net Associate Editor for Lymphoma.   You can view Dr. Flowers' disclosures at Cancer.Net. Dr. Flowers: Hello and welcome to this podcast that is a review of late breaking abstracts from the ASCO Meeting and recent updates in lymphoma. I'm Dr. Christopher Flowers, professor and chair of the Department of Lymphoma and Myeloma and Interim Division Head for Cancer Medicine at The University of Texas MD Anderson. And it's my great pleasure to discuss with you some of these late breaking abstracts. I do have some disclosures that are related to the content that I will present from this year's ASCO Meeting and recent studies in lymphomas. Those are available at Cancer.Net. Those relate to my role as a consultant for the development of clinical trials in lymphomas and research funding that MD Anderson has received from companies related to my role in clinical trials in lymphoma and clinical trials across cancers. So, the ASCO Meeting had a host of new information that was presented. Some of that information centers around key clinical trials. One that was a pivotal clinical trial, the SHINE clinical trial, looked at patients with mantle cell lymphoma, a rarer lymphoma subtype, that looked at the combination of bendamustine and rituximab, a standard chemoimmunotherapy combination, compared to that same chemoimmunotherapy combination, bendamustine, rituximab, plus the Bruton's tyrosine kinase inhibitor ibrutinib. Ibrutinib, as some of you may know, is a kind of therapy that is typically used in the relapse setting for patients with mantle cell lymphoma when they have their disease come back. And the SHINE clinical trial was looking at adding it to frontline therapy. What this randomized, controlled trial in the phase 3 setting found was that patients who received the combination of bendamustine, rituximab, plus ibrutinib had improvement in their progression-free survival, meaning that the time that it took for their disease to come back or them to have deaths related to the lymphoma was longer for patients who received this combination. About 2.3 years longer than the group that received bendamustine, rituximab, plus placebo. And in total, that led to a median progression-free survival of 6.7 years. That study has now been published in the New England Journal of Medicine and was led by my colleague Dr. Michael Wong from MD Anderson. Dr. Wong also led another study that was presented at the ASCO Meeting looking at CAR T-cell therapy for patients with mantle cell lymphoma. That study has now been published in the Journal of Clinical Oncology, and it looks at brexucabtagene autoleucel, a kind of CAR T-cell therapy, where that-- the CAR T-cell therapy was successfully manufactured for 71 of the 74 patients in the trial. 68 of those patients received an infusion and the median progression-free survival, so the average amount of time that it took for patients to have progression of their disease, was about 25 months. And so a marked benefit for those patients who were receiving CAR T-cell therapy when their mantle cell lymphoma came back. There also were major breaking abstracts at the ASCO Meeting in the area of diffuse large B-cell lymphoma. As many of you may know, diffuse large B-cell lymphoma is the most common type of lymphoma that occurs in the United States. And there was a breaking trial that was presented in December at the American Society of Hematology Meeting describing polatuzumab, a CD79b antibody drug conjugate, as a new drug in the substitution of frontline therapy for patients with diffuse large B-cell lymphoma in combinations with rituximab, cyclophosphamide, adriamycin, and prednisone, or the pola-R-CHP arm, that compared favorably to rituximab and CHOP chemotherapy, which has been the standard of care for patients with diffuse large B-cell lymphoma. And that trial showed an improvement in progression-free survival. At this year's ASCO Meeting, Franck Morschhauser presented results from looking at subsets of that patient population. Those patients who had BCL2 by immunohistochemistry that was positive or MYC expression by immunohistochemistry that was positive, or both of those, what we call double-expressor lymphomas, those who have poorer risk than standard groups. And those double-expressor lymphomas, treated with pola-R-CHP, had improvement in progression-free survival compared to R-CHOP with a hazard ratio of 0.64 in that group. We also saw in a multitude of analysis that that supported the benefit of pola-R-CHP in patients with both BCL2-positive and MYC-positive diffuse large B-cell lymphoma. Another area that has been very hot in diffuse large B-cell lymphoma clinical trials is the role of bispecific antibodies. Bispecific antibodies are antibodies that bind both to CD20, a marker on the diffuse large B-cell or the lymphoma cells, and to the marker CD3, which is a marker on T-cells which brings the normal T-cells of the immune system in close proximity to the lymphoma cells and then leads to immune-directed killing of lymphoma cells. The agent glofitamab is an agent that was presented by Michael Dickinson at this year's ASCO Meeting in an abstract. And in this study, 107 patients who received more than 1 dose of steady treatment went on to have complete responses in about 35% of patients. And this showed that glofitamab induced durable complete responses and had a very favorable safety profile in patients with relapsed and refractory diffuse large B-cell lymphoma. And in this trial, they compared that also for patients who had prior exposure to CAR T-cells and showed that responses were also good in those patients. Another set of studies has also looked at bispecific antibodies and a whole host of other areas with multitude of other agents. Another study that was presented at this year's ASCO Meeting explored the use of bispecific antibodies in the frontline setting in combination with the R-CHOP regimen that I just discussed. In that study, Lorenzo Falchi presented results of the subcutaneous bispecific antibody epcoritamab in combination with R-CHOP. This was a relatively small study of 33 patients that showed that the combination of epcoritamab plus R-CHOP was something that was safe and tolerable. There were no new treatment emergent adverse events that led to discontinuation of epcoritamab in the study. And there are some adverse events that are of special interest that we see with the bispecific antibodies, and those include the kind of immune-mediated adverse events that we can also see with CAR T-cells, like cytokine release syndrome, or CRS, or neurologic toxicities that we can see there that are also called ICANS. What we've seen in this trial, that about 42% of patients had some form of cytokine release syndrome, but that most severe form of cytokine release syndrome, those that were greater than grade 3 in severity, was only in 3% of patients. And likewise, the neurologic toxicities, or ICANS, that were grade 2 was in only 3% of patients. Relatively few patients completed all therapy by the time that this was presented. Only 10 patients had completed 6 cycles of therapy, but that showed an overall response rate that was quite high in that patient population. There were a whole host of other trials that were presented at this year's ASCO Meeting, and those portend improved kinds of outcomes on the horizon for patients with lymphomas across the spectrum. And I think it's an exciting time moving forward for clinical trials in lymphoma and hopefully, to see new therapies that emerge for the management of this disease. One of those new therapies that happened outside of the ASCO Meeting was the recent FDA approval of CAR T-cell therapy in the relapse setting for follicular lymphoma. And this was based on the ELARA clinical trial. And I think the future is quite bright for therapies and for patients with lymphomas broadly. ASCO: Thank you, Dr. Flowers. Finally, Dr. Daniel Mulrooney will discuss new research in childhood cancers, including a study comparing treatment options for Ewing sarcoma, and several studies on neuroblastoma. Dr. Mulrooney is an Associate Member in the Division of Cancer Survivorship at St. Jude Children's Research Hospital. He is also the Cancer.Net Associate Editor for Pediatric Cancers. You can view Dr. Mulrooney's disclosures at Cancer.Net. Dr. Mulrooney: My name is Dr. Dan Mulrooney from St. Jude Children's Research Hospital. I'm the Deputy Director of the After Completion of Therapy Clinic at St. Jude and primary care for survivors of pediatric solid tumors. The annual ASCO Meeting is typically quite busy and full of research presentations sharing knowledge and advances in cancer treatment and care. Today, I'd like to highlight some of the exciting presentations in pediatric cancer. Please note, I do not have any relationships to disclose related to any of these studies. At this year's meeting, one of the highlights was a European study in patients with relapsed or refractory Ewing sarcoma. Ewing sarcoma is a rare bone cancer that typically occurs in adolescents or young adults. While challenging to treat, it is difficult to cure in patients who have relapsed, and studies are needed to improve the care of these patients. Investigators from 13 European countries and Australia and New Zealand studied the most common relapsed therapies, which include irinotecan and temozolomide, gemcitabine and docetaxel, topotecan and cyclophosphamide, or high-dose ifosfamide. The study enrolled 451 patients between 2014 and 2021 and randomly assigned them to one of these four treatments. Based on response rates, the first 2 arms were dropped and the study was largely a comparison between topotecan cyclophosphamide and high-dose ifosfamide. The main outcome was event-free survival. Event-free survival is a common way in a clinical trial to see how well a treatment works. It measures the time from treatment that the patient remains free of complications, such as return or progression of the cancer. But investigators also looked at overall survival, toxicity, and quality of life. The 6-month event-free survival was better for high-dose ifosfamide at 47% compared to 37% for topotecan cyclophosphamide. The median overall survival was also better for high-dose ifosfamide compared to topotecan cyclophosphamide. The results were best for children younger than 14 years old versus those 14 or greater. Toxicities included fever and neutropenia, nausea, vomiting, and diarrhea. Patients receiving high-dose ifosfamide had more neurologic and kidney toxicities, which might be expected since ifosfamide is known to affect these organ systems, while only descriptive measurements of quality of life appeared higher for those children treated with high-dose ifosfamide compared to topotecan and cyclophosphamide. The strength of this trial is its large size, particularly for a rare cancer, and the fact that it randomized patients to the most commonly used treatment regimens for relapsed Ewing sarcoma. Importantly, data did not previously exist comparing these different treatments. While the results of this study are promising, clearly more needs to be done, and there was a lot of discussion at the ASCO Meeting about how to further improve survival in these patients. This study provides some information for doctors and patients, but importantly, provides data to advance future trials, which will concentrate on incorporating new targeted drugs with high-dose ifosfamide. This study is ongoing and is adding additional arms to continue to improve the outcomes for patients with relapsed or refractory Ewing sarcoma. In addition to this study in Ewing sarcoma, several studies investigating neuroblastoma were presented. Neuroblastoma is the most common extracranial solid tumor in children and for children with high-risk disease requires intensive and prolonged treatment, including chemotherapy, surgery, radiation therapy, and stem cell transplantation. Treatment for these patients has improved since the introduction of immunotherapy, particularly an antibody directed at a particular antigen named GD2 on the neuroblastoma cells. One study showed improvement in outcomes using this antibody for children with relapsed or refractory neuroblastoma, and another study demonstrated feasibility of using this antibody earlier in treatment, which was not previously known to be safe and tolerable. In what is called the BEACON study, investigators tested whether the antibody, called dinutuximab, would be effective when combined with chemotherapy for relapsed or refractory neuroblastoma. They enrolled 65 patients from 2019 to 2021 and randomized these patients to either chemotherapy alone or chemotherapy plus dinutuximab. The median age of these children was 4 years. The overall response rate, which means either a complete or partial response, was 18% for the chemotherapy-only arm but improved to nearly 35% for those treated with chemotherapy and dinutuximab. The progression-free survival was 27% for chemotherapy only and improved to 57% for those treated with chemotherapy and the antibody. There was no change in overall survival, though investigators think this may have been due to some patients who had progressive disease and crossed over to the antibody arm of the study. This presentation was followed by a study from the Children's Oncology Group, which investigated the feasibility of adding antibody treatment earlier in the treatment regimen for neuroblastoma. Prior studies had used antibody later in treatment when the tumor burden is thought to be lower. The endpoint of this study was tolerability measured by toxic deaths or unacceptable toxicities, such as adverse reactions to the medication. For example, sustained low blood pressure requiring a ventilator or breathing machine, or severe neuropathy. 42 high-risk neuroblastoma patients were enrolled from 8 different children's hospitals between 2019 and 2021. 41 of the 42 were able to complete the induction chemotherapy plus the antibody. There were no toxic deaths or unacceptable toxicities. Importantly, 85% were able to complete the next phase of treatment, called the consolidation phase, and 79% were able to complete the following phase after consolidation, called post-consolidation. One-year event-free survival was 83%, and 1-year overall survival was 95%. Now, it's important to know these are still early results, and the trial recently closed, and some of the patients have only completed therapy within the last year. Both of these studies add to the knowledge of chemoimmunotherapy for children with high-risk neuroblastoma. These studies provide a foundation for larger randomized trials that will further advance the care of these children. And finally, another study looked at race, ethnic, and socioeconomic disparities among children treated for high-risk neuroblastoma on Children's Oncology Group studies. There were no differences in event-free survival, but there were differences in overall survival based on ethnicity. The 5-year survival was lowest for Hispanic patients at 47%, 50% for non-Hispanic other ethnicities, which included Asian, Native American, Native Hawaiian, or Pacific Islanders, and 62% for non-Hispanic Black and non-Hispanic White children. Importantly, these investigators also studied household and neighborhood poverty. Overall, survival was lower for children living in poverty, though some of these differences went away when accounting for other factors, such as stage of disease or high-risk features. This study is important because it highlights the increasing need to collect data on clinical trials that may contribute to inequities in outcomes. While most studies collect data on the race and ethnicity of participants, other factors known as social determinants of health, such as income, neighborhood, education, access to health care, and insurance coverage, may also contribute to outcomes in pediatric cancer patients. Overall, the studies highlighted here and presented at this year's ASCO Annual Meeting focused on difficult-to-treat cancers, such as relapse or refractory disease, and they have laid the groundwork for future investigations to continue to improve survival rates for all children diagnosed with a malignancy through improved therapies and by addressing potential social barriers. Thank you for listening to this brief summary of the new research in pediatric oncology presented at the 2022 ASCO Annual Meeting. ASCO: Thank you, Dr. Mulrooney. You can find more research from recent scientific meetings at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

Back in May 2019, MTPConnect launched the Biomedical Translation Bridge (BTB) program, a $22.3 million initiative of the Medical Research Future Fund, supporting the translation of new therapies, technologies and medical devices through to the proof-of-concept stage. In a first for Australia, it did that by pairing funded projects with industry mentors and commercialisation experts.Three years on and a COVID-19 pandemic later and the program is now moving to completion. To celebrate this milestone, we brought together the 21 funded projects and our venture and education partners, Biocurate, UniQuest, Medical Device Partnering Program and the Bridge and BridgeTech programs, for the BTB Finale event at Luna Park in Sydney. In part two of this episode, hosts Caroline Duell and Dr Duncan Macinnis walk the floor catching up with awardees and partners. We hear from Dr Alison Thistlethwaite from Melbourne-based biotech MycRx - developing first-in-class small molecule inhibitors of the Myc oncoprotein as safe and effective treatments for cancer. Dr Jeremy Paull from Melbourne biotech Starpharma talks about how the funding supported the development of their anti-viral nasal spray, Viraleze™  within 12 months which is now registered for sale in more than 30 countries. And venture partners Dr Mark Ashton from Uniquest, the Biocurate team of Linda Peterson, Dr Tifelle Reisinge and Dr Eric Hayes, and BridgeTech's Professor Lyn Griffiths explains how they bring their expertise in commercialisation to assist BTB projects reach commercialisation stage. 

My C train runs from 168 St to Lefferts via 8th Ave & Central Park West Express and Fulton St local. All A train service goes to Far Rockaway.  I am deleting my discord. --- Send in a voice message: https://anchor.fm/savion-divino/message

Myc Tyson is on a mission to spread the word about fungi to every person on the planet! Myc has demonstrated this by starting the hugely successful subreddit r/Mushroomgrowers back in 2015, starting an online mushroom culture business, and orchestrating various mycophilanthropy projects - giving back to the world via the power of Mushrooms. Click the links below to learn more about the work Myc has done in Kenya. This was such an awesome conversation and Myc is doing some really important work in the field of mushrooms. As always, let us know what you loved, what we missed, and who you want us to bring on the show next time. Thanks for watching! Chapters:0:00 Framing the Conversation0:59 Introducing Mr. Myc Tyson! (Appreciating the Beards)4:00 Myc's Mushroom Background7:45 The Creation r/MushroomGrowers and Quitting an IT Career15:00 The Power of Lion's Mane22:58 Mycophilanthropy33:03 Growing Mushrooms at Home40:40 Mushrooms Find a Way44:47 The Pros and Cons of Myco-preneurship50:57 The Secret Sauce for Agaricus Farming55:20 The Doorway to Mycology & Mike Tyson Himself1:01:50 How to Connect with MycListen on Spotify: https://tinyurl.com/2p8aks8cLinks:Myc's Website: https://myctyson.com/Hericium Labs: https://www.hericiumlabs.com/Eco Agric Uganda: https://www.ecoagricuganda.org/

This episode is sponsored by BTG Speciality Pharmaceuticals. BTG provides rescue medicines typically used in emergency rooms and intensive care units to treat patients for whom there are limited treatment options. They are dedicated to delivering quality medicines that make a real difference to patients and their families through the development, manufacture, and commercialization of pharmaceutical products. Their current portfolio of antidotes counteracts certain snake venoms and the toxicity associated with some heart and cancer medications. Their drug, Voraxaze, is for high-dose methotrexate toxicity. This talk will focus on research elucidating MYC amplification as the first genomic prognostic biomarker in osteosarcoma, which may be used for risk stratification in future clinical trials and to inform conversations with patients and families. Dr. Marinoff will discuss the tools used to detect MYC amplification, what we have learned about its association with outcome in children/ young adults with osteosarcoma, and what we still don't know but are trying hard to find out: the biological roles of MYC amplification in driving osteosarcoma and how it may serve as a potential therapeutic target in the future. Dr. Marinoff graduated from Harvard Medical School and completed her pediatric residency at Boston Combined Residency Program, during which time she worked with Dr. Katie Janeway on elucidating the genomic landscape of and novel genomic biomarkers in osteosarcoma. She is currently completing her fellowship training in Pediatric Hematology/Oncology at UCSF, where she is focused on developing novel genome-informed therapeutics for osteosarcoma under the mentorship of Dr. Alejandro Sweet-Cordero. She plans to develop an active clinical and translational research program focused on conducting early phase precision medicine-oriented trials for patients with advanced sarcomas. She is grateful to have the best job in the world.

News: NASA Solar Sail Spacecraft to Chase Tiny Asteroid After Artemis I Launch | SciTechDaily (01:25) Launching with the Artemis I uncrewed test flight, NASA's shoebox-size Near-Earth Asteroid Scout will chase down what will become the smallest asteroid ever to be visited by a spacecraft. The asteroid being targeted is, 2020 GEnear-Earth asteroid (NEA) that is less than 60 feet (18 meters) in size Asteroids smaller than 330 feet (100 meters) across have never been explored up close before. The spacecraft will use its science camera to get a closer look, measuring the object's size, shape, rotation, and surface properties. It will ride as one of 10 secondary payloads aboard the powerful Space Launch System (SLS) rocket, which will launch no earlier than March 2022. After it is dispensed in space it will use stainless steel alloy booms to unfurl a solar sail that will expand from a small package to a sail about the size of a racquetball court, or 925 square feet (86 square meters).Will generate thrust by reflecting solar photons – quantum particles of light radiating from the Sun Sunlight acts as a constant force, so a tiny spacecraft equipped with a large solar sail can eventually travel many miles per second. Maneuver by tipping and tilting its sail to change the angle of sunlight The mission will act as a nimble scout for future human and robotic missions that may utilize asteroid resources – and will gain important planetary defense insights about this class of NEA. Julie Castillo-Rogez, the mission's principal science investigator, provides insight as to why looking at even small asteroids are important:“Although large asteroids are of most concern from a planetary defense perspective, objects like 2020 GE are far more common and can pose a hazard to our planet, despite their smaller size.”   Altos bursts out of stealth with $3B, a dream team C-suite and a wildly ambitious plan to reverse disease | FierceBiotech (08:11) Early details of Altos leaked out last year when MIT Technology Review reported Jeff Bezos had invested to support development of technology that could “revitalize entire animal bodies, ultimately prolonging human life.” The official reveal fleshes out the vision in more detail Hal Barron, M.D, the future CEO of Altos, provided a statement on the company:“It's clear from work by Shinya Yamanaka, and many others since his initial discoveries, that cells have the ability to rejuvenate, resetting their epigenetic clocks and erasing damage from a myriad of stressors. These insights, combined with major advances in a number of transformative technologies, inspired Altos to reimagine medical treatments where reversing disease for patients of any age is possible.” Yamanaka is a 2012 Nobel Prize winner for the discovery of the ‘Yamanaka factors' — four transcription factors (Oct3/4, Sox2, c-Myc and Klf4) that can reprogram cells to roll back cellular aging and repair tissues.  Altos is bringing in the biggest names in life sciences to staff out their C level positions at the company. The team will use $3 billion in capital committed by investors to turn breakthroughs in our understanding of cellular rejuvenation into transformational medicines.  Co-founder, Rick Klausner, M.D., stated in a press release:"Remarkable work over the last few years beginning to quantify cellular health and the mechanisms behind that, coupled with the ability to effectively and safely reprogram cells and tissues via rejuvenation pathways, opens this new vista into the medicine of the future. Altos begins with many of the leading scientists who are creating this new science. Together, we are building a company where many of the world's best scientists can collaborate internally and externally and develop their research with the speed, mission, and focus of private enterprise. Our success will depend upon a culture of intense collaboration, enthusiasm, and openness." David Baltimore, PhD, a board member provided a positive goal Altos is shooting for:“The goal of Altos will be to reverse the ravages of disease and aging that lead to disability and death, reinvigorating and extending the quality of life. Altos will provide an unparalleled environment for collaborative discovery and has already attracted a most impressive group of investigators to the daunting task of reversing ill health and taking medicine in a new direction.”   Patient-specific spinal model may predict the effect of disc implants | New Atlas (16:28) As people get older, the intervertebral discs in their spine tend to deteriorate, some of which end up being surgically replaced with implants. Who doesn't know someone that has a bad back? A new patient-specific spinal model by scientists at Florida Atlantic University, could help determine how successful such surgery will be. Process:Obtain a CT scan of a patient's spine Create a 3D computer model from the scan Produce a 3D-printed model of one section of the spine with a cervical disc implant already in place Utilize a robotic arm to flex and extend the spinal replica, simulating five different real-life spinal postures Sensors then monitored the manner in which the added implant was causing stress to be distributed throughout the spine. The setup was found to be 100 percent accurate at replicating the effects that the postures would have on the real spine, with the addition of the implanted disc. Once developed further, the technology could be used to determine what sort of implant and/or surgical technique would work best, before the surgery is performed. Additionally, simulations could provide information as to what movements are best while recovering from the surgery.   Intel Is Investing $20 Billion Towards a Massive New Semiconductor Plant | Interesting Engineering (21:10) According to a Reuters report, Intel is set to invest $20 billion into a massive new semiconductor chip manufacturing site near Columbus, Ohio. All coincides with a recent analysis informing that China is "three or four generations" away from being at the cutting edge of semiconductor production. Chipmakers worldwide are frantically trying to boost output amid the global chip shortage brought on by massive demand and supply chain disruption fueled by the pandemic. Intel's new investment will go towards building two new semiconductor manufacturing plants, bringing 3,000 new permanent jobs to the 1,000-acre site in Albany, OhioThe first step in building an eight-factory complex that could cost additional tens of billions of dollars. Intel also recently announced plans for another U.S. campus site that would begin construction before the end of the year.The new site, according to reports, could cost $100 billion and eventually employ 10,000 people.   Elon Musk's brain chip firm Neuralink lines up clinical trials in humans | The Guardian (27:10) The billionaire entrepreneur Elon Musk's brain chip startup is preparing to launch clinical trials in humans. This is stemming from a job post for Neuralink for a “Clinical Trial Director.” What is mentioned in this post?“As the clinical trial director, you'll work closely with some of the most innovative doctors and top engineers, as well as working with Neuralink's first clinical trial participants …. You will lead and help build the team responsible for enabling Neuralink's clinical research activities and developing the regulatory interactions that come with a fast-paced and ever-evolving environment.” Just last month, Elon Musk, mentioned his optimism in allowing quadriplegics to move again:“We hope to have this in our first humans, which will be people that have severe spinal cord injuries like tetraplegics, quadriplegics, next year, pending FDA approval … I think we have a chance with Neuralink to restore full-body functionality to someone who has a spinal cord injury. Neuralink's working well in monkeys, and we're actually doing just a lot of testing and just confirming that it's very safe and reliable and the Neuralink device can be removed safely.” The company is also recruiting for a “clinical trial coordinator” to help build a team of people to run the trial and liaise with regulators.  These applicants, according to the posting, have an “opportunity to change the world and work with some of the smartest and the most talented experts from different fields”.  

Dr. Dean Felsher from Stanford University School of Medicine, Departments of Medicine and Pathology and member of Oncotarget's Founding Editorial Board, talks about the editorial process at Oncotarget. DOI - https://doi.org/10.18632/oncotarget.22342 Correspondence to - Dean W. Felsher - dfelsher@stanford.edu Keywords - liver cancer, HCC, miR, MYC, lipid nanoparticle (LNP) About Oncotarget Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Multiple Sclerosis News Today's multimedia associate, Price Wooldridge, discusses an article about how increasing the activity of the Myc gene can make myelin-repairing cells more efficient, a finding that may help advance MS treatments, a study says; and reads the column by John Connor, Fall Down, Get Up Again, “I'm Back in the Desert Without a Horse”. =================================== Are you interested in learning more about multiple sclerosis? If so, please visit: https://multiplesclerosisnewstoday.com/ ===================================== To join in on conversations regarding multiple sclerosis, please visit: https://multiplesclerosisnewstoday.com/forums/

Oncotarget Volume 11 Issue 15 reported that several zebrafish T-ALL models have been reported, but until recently, robust D. rerio B-ALL models were not described. Here, the Research Team has shown new B-ALL findings in one of these models, fish expressing transgenic human MYC. They describe B-ALL incidence in a large cohort of hMYC fish, and show B-ALL in two new lines where T-ALL does not interfere with B-ALL detection. Dr. J. Kimble Frazer from the Department of Cell Biology and the Department of Pediatrics, Section of Pediatric Hematology-Oncology, as well as the Department of Microbiology & Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA said, "Acute lymphoblastic leukemia (ALL) and the related malignancy lymphoblastic lymphoma (LBL) dominate pediatric oncology, together representing over one third of all childhood cancer." For T-ALL in particular, zebrafish models have been highly informative, advancing our understanding of T-ALL genetics, pro- and anti-oncogenic interactions between different genes and pathways, tumor heterogeneity, leukemia stem cells, and in screens for new therapeutics. However, despite the fact that zebrafish T-ALL models had proven to be fertile grounds for study, B-ALL modeling in D. rerio had not been fruitful, with only one low penetrance and long latency line reported. This was curious because zebrafish recombination activating gene 2 promoters active in both immature T and B cells was used to regulate most of these transgenic oncoproteins in the various T-ALL lines, yet D. rerio B-ALL had not been reported in them. In 2018, the zebrafish ALL field advanced suddenly with reports of B-ALL in two closely-related transgenic lines where T-ALL was already known to occur. Here, the authors present new results in the hMYC model, including B- and T-ALL latency and penetrance data in a cohort of over 600 animals, in vivo glucocorticoid and radiation treatment of B-ALL, and expression profiles from single B- and T-ALL cells. The Frazer Research Team concluded in their Oncotarget Research Perspective, "We postulate these and other differences may explain the apparently disparate oncogenic mechanisms employed by hMYC and mMyc in the B lymphoblasts of these closely-related lines. Pathway analysis of differentially-regulated genes predicted differing activation of several biologic pathways (e.g., cell differentiation, immune system process, lymphocyte activation, RNA binding, etc.; Figure 6B panels and Supplementary Table 4). These markedly different pathway signatures further demonstrate that human and murine MYC are far from synonymous in terms of their oncogenic effects upon zebrafish B lymphoblasts." Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27555 DOI - https://doi.org/10.18632/oncotarget.27555 Full text - https://www.oncotarget.com/article/27555/text/ Correspondence to - J. Kimble Frazer - Kimble-Frazer@ouhsc.edu Keywords - acute lymphoblastic leukemia, ALL, zebrafish, lymphocyte, MYC About Oncotarget Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Not totally sure what those poker graphs with red, blue, and green lines mean? In this episode, we explain everything you need to know about the red line, the blue line, stats like “My C all-in adj”, and more. Concepts include understanding graphs with higher red lines, “normal results”, and why the EV line should just be ignored. Take A Free Trial Of PokerTracker 4: https://www.splitsuit.com/visit/pokertracker 4 Question To Ask Before C-Betting: https://redchippoker.com/4-questions-before-c-betting/ Start The CORE Poker Course: https://redchippoker.com/launch-core/ Be sure to join our free Discord as well to post hands, ask questions, and join a community of players who love poker as much as you do: https://redchippoker.com/discord

En esta ocasión, Laura Soucek, científica y emprendedora que tiene como misión acabar con el cáncer, nos cuenta cómo ha creado el primer fármaco capaz de inhibir la proteína Myc, la cual se encuentra vinculada a todos los tipos de cáncer. Notas del Episodio: CLUB: https://yoemprendedora.es/club/ Notas del podcast: https://yoemprendedora.es/la-emprendedora-que-quiere-acabar-con-el-cancer/

Intro: Gina ordered her theatre school transcriptsLet Me Run This By You: knowing when to let go, moments of clarityInterview: We talk to Ammar Daraiseh about being an MFA, homesickness, Joe Slowik and Bella Itkin, Joe Mantegna, type casting, being a middle eastern actor, Sweet Smell of Success, film noir. www.ammardaraiseh.com - there is where you can watch Ammar's acting reel and my short films he produced www.karenkanas.com - Ammar's wife's website FULL TRANSCRIPT (unedited):2 (10s):And I'm Gina . We went to theater school1 (12s):Together. We survived it, but we didn't quite understand it. 20 years later,2 (16s):We're digging deep talking to our guests about their experiences and trying to make sense of it all1 (21s):Theater school. And you will too. Are we famous yet?2 (34s):Frog into my, my morning frog out of my throat yet. How you doing? I am. Wow. I have a lot to talk to you about, oh, I1 (45s):Half expected you to have red hair this morning.2 (49s):Oh, do you think I should. I okay. But like, did you see the picture? I put a run Lola run. I mean, that might be a little hard to maintain.1 (59s):It's super hard to make, like you'll, you'll have to be the salon and read six weeks at least, or four weeks for root touch-up. But I mean, I personally think the routes coming in would look cool, but wow. Yeah,2 (1m 13s):The whole rally thing. Well, I'll keep you posted cause I, I definitely want to do something different, much different what's going on. Okay. So first thing I'll just get out of the way is for fun, because we're always trying to remember our classes and who taught and what gear we did, everything I ordered my transcript, which unfortunately does not have the names of your professors. Just, yeah, it just has the name of the class and my grades were fair, not great. Like I had a 3.5 or something like that, which I would have, I thought in my memory that I got really good grades in college, but they were really just pretty average.2 (2m 1s):But guess what my lowest grade was in1 (2m 8s):Was it, was it, well, the easy choice is add Colleen,2 (2m 13s):My C my, my one and only see mine was an intro to psychology. I was talking to my husband about it and he goes, yeah, I got a low grade too. He's like, we were just basically saying, this is all too real. We're not ready yet. I think1 (2m 40s):That's a great observation by him.2 (2m 44s):See my whole areas. It's just hilarious. And then in other classes where I was sure, you know, I was hated like an alcohol use class in that I got A's so my God isn't that it's also subjective, like our, our experiences, something as subjective and then our memory about something totally changing. Only subjective as the years go by. Right.1 (3m 7s):It's not just subjective. It's yeah. It's very like mutating subjects, right? Yeah. That's crazy. Oh my God. So you ordered your transcript. Okay. Now you have a transcript2 (3m 21s):And guess what? Anybody can, it's 25 cents. Like if you have, if you haven't ordered, like you have a certain number, you can get in a certain period of time. And so your first one is 25 cents. You,1 (3m 33s):Anybody else want to have a transcript? You2 (3m 36s):Could relive your, your grades. Oh my gosh. Might find some surprises. Do you think you would find some surprises in your1 (3m 42s):I'm? Sure. I mean, I know for a fact that I, that I, I was supposed to drop a class, a, a non, obviously non theater school class, and I never dropped it. So if you don't drop it, you get an F. So I got an F in, like, I want to say it was like sociology or something like that. And I almost didn't graduate because they thought, yeah. And so you can't, I knew it was like, I remember my last year, my senior year, I had to like, do all kinds of regular role. And the other thing is that I didn't do was one year, one quarter or something you had to like re up your financial aid and I didn't do that.1 (4m 24s):So I didn't pay for like a quarter. And they were like, yeah, you're, I'm so shocked. I graduated. I don't know what was happening. They were like, yeah, you have to pay.2 (4m 35s):I had to do some real tap dancing to my parents graduate.1 (4m 39s):Yeah, I remember that, but I don't. Yeah. I I'm sort of scared to look at the grades. I don't.2 (4m 46s):Yeah. I mean, whatever, it's like a grade and acting school is just kind of funny. It should probably be, and maybe at some schools it is pass, fail. It just should be pass, fail. Like you either got it. Or you didn't get it. You either write forth effort or you didn't. Right. So that's kind of, wow. Okay. And update on surprises. Because last week I was saying like, I'm open to surprise. And it worked, which is to say, I think pretty much not that like some big surprise came falling out of the sky, like is what, the thing that I was really after. But instead I did, I took my own advice and like pursued, doing something differently.2 (5m 27s):And on Saturday we ended up, I just on Friday night when Aaron came home, I said, I want to have fun tomorrow, but I've got to get out of this house. I've got to get out of this town. And so he searched up like fun things to do. And he found something which actually was terrible, but it didn't matter because it was different. And we, it was a car. It was, it, it was promoting itself as some like amazing fall festival with all this kind of stuff. And it was literally a carnival, like the Carney trucks. It's amazing.1 (6m 7s):Like, yeah. Right. Oh, well they had some good marketing.2 (6m 11s):Yeah, they sure did. Cause it was listed as the number one thing to do in my state this weekend, the state and the state and the state. But even, maybe it was a slow weekend and we had fun. Anyway, we had fun. We went to a town we've never been to, we spent time together. You know, it, it was fine. It was good. And more importantly, I feel like it, it just doing something like that and genders like, okay, what else can you do? What else? You know? So I think that, that was the important thing is that it opened me up to1 (6m 43s):Novelty. Did anyone else, did anyone get hurt on a ride?2 (6m 48s):No, but the whole time I was like, I bet this is going to be one of those times where one, we're one of these things just going to go flying off into the, so if you really want to call it,1 (6m 58s):If you really want to go down a crazy dark rabbit hole, like, okay, well I'm obsessed with fail videos fails. You know, if you watch carnival fails. Oh my God. And most of them are deadly. Thank God. But they're just like, where thing flies off. Or like, like a lot of times what you have is cell phones going crazy or birds like birds attacking people on rollercoasters is one of my favorite things to watch. It's not that the bird is attacking. It's at the bird is just trying to fucking fly. And it runs smack into a person on rollercoaster, the best thing you've ever seen.1 (7m 38s):But the sad thing is 90% of the time the bird dies, you know? But like, because the velocity, the force is so great, but it's pretty freaking funny. People are filming themselves usually like right then all of a sudden, a huge pigeon like common. So carnival fails is, is one thing where like someone's standing there like videotaping their friend on the tilt, a whirl or whatever the hell it is and a bolt or something goes with. And they're like, oh, that was a part of the ride. So2 (8m 13s):You're standing there as an adult. I mean, as a kid, you're just like, this is the most amazing thing ever. But as you're sitting there as an adult, you just can see like the hinges where things fold up into the, you know, and you're just like, this is just, we're just all hoping that nothing bad happens, right. Best you can do is cross your fingers and hope for the best. Right.1 (8m 33s):And the other thing is that I I'm obsessed with watching is those Slingshot videos. So some people pass out, pass out or like people's weaves fall, fly off and like, or, well, yeah, like people pass out, but I like when things fly off or when just people say really weird stuff or like, yeah. But those2 (8m 55s):Slingshots are horrible. They look horrible ever. I would never, of course, of course, where I'm sure many people have been slung right off into an alligator pit ever at the museum again. Oh, that's crazy. Okay. So the, the big O thing that changed for me since I last talked to you and I'm fighting the urge since yesterday to call you for the podcast, I haven't heard the podcast. Well, I wrote down the headline is I'm going to do this in a politic way organization on the brink of collapse, ALEKS new leadership to ensure its future spends next two years, undermining their, every effort says leadership.2 (9m 40s):We quit. I have quit the organization organization that I have dedicated a lot of hours to serving. And it happened. Yeah. It happened after a meeting last night that went left and it didn't even honestly, as these things, are, it didn't even go as left as it's gone. There's been times where it's gone so much further skew, but all of us just had it. And actually after our interview today, I have, we have an emergency meeting to talk about it, but my decision is made, I quit.2 (10m 25s):I fully quit. Like I'm, I'm happy to help transition or whatever. And yeah, that happened inside. Like how did you come to the, like what happened in, what have you? Yeah. So this is kind of like a combination, just like what I wanted to talk to you about. And then also what I want to run by you because, you know, I just wrote that blog post about like how I meant examining myself in relationships and how I sometimes in the past have just, you know, one day just up and left. And the first time I did that, that felt the way that actually this thing felt last night was when I broke up with my first boyfriend in high school, it was literally like I was asleep.2 (11m 10s):I shot up out of bed, like in a movie. And I said, I've got to break up with this guy. And I got my clothes on and I got in my car and I drove over to his house and I walked into his house. I didn't knock the door. I walked in the house, he was in the bathroom getting ready. I, I had a little box of his shit. I go here by, I walked, he's following help cheetah. What's the matter, what's the matter. And I left. I mean, we, we did speak after that. And actually I had a couple of really crazy incidents with him even like later in life when I ran into him as an adult. But, and you know, that was terrible of me to do that was terrible.2 (11m 51s):But now I understand that it was because I lacked the ability to say along the way I don't like this. And I don't like that. And just kind of kept putting up with it and putting up with it. And I think my big takeaway from how I conducted myself in this organization is that I put up with stuff and put up with stuff that I really should have found more backbone along the way to say, I don't like the way you're talking to me. I don't like the way you're treating me. And in fact, I had the group of people that I work with. It I'm basically the leader of, you know, they were constantly expressing to me that they felt really abused by this group. And I would validate that and listen to them and agree with them.2 (12m 36s):But then when it came time to going back to the group, I fell short of saying, this will not stand. You know what I mean? I never did that. I never put my foot down and said, this that's enough because I was trying to do it in this way that I feel you're kind of supposed to do as a leader of something you're supposed to keep a level head. And it's really, frankly, it's a lot like being a therapist, you take people's projections and you take their shit and you, and you're able to see, okay, this thing is about me. This thing is not about me. This is just you projecting your shit onto me and you try to like, keep it moving for.2 (13m 17s):Good. Great. And it's not that we never responded with, like, this is not a feedback. Yeah. But it, I mean, obviously it didn't work. It didn't get us to where we needed to go. So we ended the meeting yesterday. I stayed on and talked to my cohort. I said, you guys, I'm, I'm done. And there was seven of us and only four of us were, were talking after cause or five of us. So there was two people who had no idea, but, but four of us said, we're ready to, oh.2 (13m 58s):And I spent three hours last night writing a letter that just basically told the whole history and laid it out. Exactly why, you know? And I wrote it as like, we came to this decision. I don't know if we're coming to this decision because we have to have our meeting later and I just laid it all out. And I just said, you know, basically we're at cross purposes here. Like you asked us to do something that we are doing and you don't like the way we're doing it. So it's fundamentally not going to work out. Wow. I was all revved up. I stayed awake until two 30.2 (14m 38s):Sure. Yeah. I've been there got three hours of sleep. Holy shit. Feeling great. 1 (15m 0s):Good for you. I mean, I think the other thing is like, yeah. I mean, I think that when things, something isn't working, yeah. I've always struggled with knowing when to, when to leave something and like when to, I never knew, okay. Like even stupid shit, like staying home, sick from school. So like, my mom always taught us, like, you never do that unless your like hand is falling off and even then you try to go. But so then in my adult life, when I never knew when was the time to listen to yourself?1 (15m 43s):Yeah. Or to call it quits. Yes. Right, right. To listen to myself or like, was that, and I always second guessed myself for a long time. And even like, like I remember having like a date, you know, with, with a friend or she was really like a mentor, like an authority figure. That's always when it gets really kicked up. And I didn't know, like if I was sick or just wasn't feeling off, should I cancel? Would they be mad at me? Would I, could I take care of myself? What did taking care of myself look like? Because sometimes, and people would say like, people would, I would ask for advice and they say, sometimes taking care of yourself means staying home. Sometimes it means pushed through a little bit.1 (16m 25s):I never knew what, how to do that. So I never had a gauge. So it sounds like you're learning finally to like, or like you're coming to the thing of like this, this is not right. This is not working for me. And, and, and I'm going to make a bold move and then I'm going to stick by that bold move. And also knowing that like, you know, it's, it's a, it's a, it's a move that right. That you can back up that you feel done and that you don't need to ask for reassurance or like try to, but that you're done.1 (17m 9s):I mean, I think that's really great. I mean, I think it's part of being a self-actualized adult to know when something's over and, and why it's over and how to do it. Right. How to end it right by you for you versus like the right thing that people want you to do. Oh,2 (17m 27s):100% that, and that thing that you're describing about the way that we need to be able to differentiate when I'm just feeling avoidant versus when I really need to, that is such a crucial part of a person's development. And I can say, as a parent, it's pretty hard to teach because you're like, I don't know. Do you really feel sick or really just not want to go to school? Like it's, it's tricky.1 (17m 56s):I, I mean, I can't imagine doing that with someone else because I literally am just now learning at 46, how to do it with myself. So like, like I can't imagine being, because the second guessing it's so interesting. It's like, it's like my, my growing up, it was, yeah, it was literally like, you, you didn't ever, you always muscled through, but I guess the, the, the, and it's like, how do you know that muscling through is too much? What is the answer? Like, you're dead. Like, that's going to be how you found out. Like, I remember this and it wasn't just my parents.1 (18m 38s):Like I remember my aunts, my aunts had a cleaning business. Okay. My mom's sister and her and her wife, or at the time her girlfriend, they had a cleaning business. So they cleaned people's houses. And at the end of, I think it was, I don't know which some play I was in at the rescue. And it must have been, I think it had to be it wasn't yellow boat. So it had to be this other search for delicious. Anyway, I was really sick. And, you know, obviously we, we still do performances when we're sick. That's another thing that needs to change. Right. And they're trying to change people's trenches anyway, I'm sick as a dog and I I'm sick as a dog. And I, I had to schlep my shit from the Myrtle Ruskin.1 (19m 19s):And the next day I was supposed to clean houses with my aunt. Like I was helping her. She gave me like a part-time job, but I'm so sick. And the night before I call, I'm literally like, like I'm hacking up blood. It turned out I had pneumonia and I had to go to the, it, it was, it was crazy. But my aunt was so mad at me that I had to bail. She shamed me. She was like, I can't believe you let me down. I literally can't talk. And she's she? And you know, she was the adult and I was a young adult, but she was anyway, the point is it, wasn't just my parents. It's a whole thing of like, how could you leave us?2 (19m 54s):We're going to have to talk about this with Molly Smith, Metzler, who we're going to be talking to in like maybe next week or the week after who's the creator and showrunner of a major television series. That's based on a book because this theme comes up in that series. And it's, it's something related also to, I don't know. I don't really remember if you told me that your mom's family grew up with money or without money, but1 (20m 21s):Without with, with, and then without, so they, they had it in Columbia and they didn't have it here.2 (20m 27s):Yeah. So people without money, I mean, it's, it's true. The, the decision about muscling through it is really, usually one about survival. Like you don't have the option, but for people who are, you know, in our situation now, I mean, I think the only way you really learn that for yourself, whether you should stay in through or not is with experience of, well this time when I didn't feel like doing something, and then I did it, I felt better this time when I didn't feel like something doing something. And I did it, I felt worse. Like, and just trying to build up the data as to say, this is an example of a time, like just, just the ability to be able to at, at our age, we've had enough experience that we can think through almost any set of, you know, like, okay, well, if I go to this thing, like, I think you were talking about you, miles was at the hospital getting checked out for a possible recurrence of his cancer and you were doing a reading.2 (21m 32s):Oh, oh,1 (21m 33s):It was the worst. It was insane. I was in the chapel at the hospital trying to memorize lines for a fucking 10 minute play reading that was supposed to be on book. And then they told me it was off book. And then2 (21m 46s):You weren't getting paid for that. Wasn't going to advance your career in any way. Yeah. That's what I'm talking about. This is, and so the, the thing I really want to run by you is about like moments of clarity and really you can't force a moment of clarity it to me, or maybe you can, I can't, it just comes to you, you know, it just, it just comes to you for me, it comes to me in a moment and it just feels like on ambivalent, there's no question. This is what I have to do. This is what I can't do. This is what I can do. And I think the only way you get there is with time.1 (22m 25s):Yeah. Yeah. I mean, I think it's time and I think you're right. I think it's like trying it out. Like I tried this, it went horribly wrong or I tried this and yeah. And also, yeah, I think right there was this thing too, of like, there's also this thing I feel, and maybe this also goes back to the, the working class. I don't know what it is, but it's like people wanting to end things the quote right. Way. So like my, my mom was always big on like, you know, and my dad about like, having a conversation, like having to sit down with people and say, Hey, this is how I feel.1 (23m 11s):And like, it was a cop-out to like send an email or a cop-out to, but that's also kind of, garbagy like, people am things the way they can end them in the moment. And they, I don't know, I don't hold it against people for ending things the way. Look, it, would it be great if we could have closure and like, stuff like that. But like, what if, I don't know, I'm just like all for now, people doing things the way that they feel like in the moment they need to do them. Like, I don't, like I used to get into, like, I remember like leaving a sponsor relationship and she was so she was not well in my view.1 (23m 53s):And she was, and I've sent her an email and she really wanted to have a sit down. And yes, there's two things are true. Like, I was really scared to sit down with her and tell her, like, I think you're fucked up and this isn't working for me or whatever, but I also didn't feel safe enough to do that.2 (24m 10s):Yeah. Yes. That's. The other thing is if we lived in a world where it was a given that everybody was being forthright and honest and was themselves in constant dialogue about their strengths and weaknesses, and was B you know, if we lived in a world where everybody was operating from a basic level of like honesty and good intentions, then this problem would be much easier to these types of problems would be much easier to resolve because you'd say, well, I mean, it just would be a given, like, of course nobody would want to see me suffering to do.2 (24m 51s):Of course, they'd rather, you know, but you can't, that's not the situation in most cases. So you literally can only rely on your own understanding of yourself. Right.1 (25m 1s):Different context. Right. And I know that there's, there's the there that looking back, I wish I had ended things differently in a lot of different ways, but I did what I, I did what I could, you know, I did really could, but I just remember it being like my, my dad being like, you know, you should really sit down with them and talk to them and being like, you know, why like, okay, I, I hear what you're saying. So when people, yeah. I think, I think being willing to have conversations and having hard will being willing and open and available to having hard conversations with people is so much more difficult than people make it out to be.1 (25m 41s):Because like you're saying, it takes, it has all it takes. It's all these things come into play. It's not just like, I'm going to be a mature adult and do this the right way. It's like, what am I willing to have? What can I handle? You know,2 (25m 55s):W what can I handle? And, you know, in some cases, if an issue is really contentious, it becomes, you know, if I sit down with this person and really try to, they might actually further harm me. Like, I I've already had that experience with some people in this group that where I've decided, okay, the approach is I have to call this person. Right. I have to say, Hey, we're, you know, not seeing eye to eye. And a couple of times when I did that, it turned out fine. Right. And a couple of times when I did that, I thought,1 (26m 26s):Why did I do that? Yeah.2 (26m 28s):Like, not just, that was bad for me, but that was bad for them. And I feel like, I, I feel like I took us several steps backwards just because this person's mentally unwell and I'm able to have like a reasonable back and forth in a conflict.1 (26m 42s):Right. So it's, it's, it's a lot more complicated, I think, than people people think. And also right when you're done, you're done. And when you're done, it's like, how can I extricate myself and not try to cause further harm to other people, but also not trying to cause further harm to myself.2 (27m 3s):Yeah. Yeah. Which is literally, you're the1 (27m 6s):Only person who can do that. Right. That's nobody else's job. Right. Somebody else's job. Holy shit. Well, congratulations.2 (27m 14s):Thank you. So how are you doing1 (27m 16s):Well, this is, I'm pretty good. I'm on, I'm so weird. I don't even know. I don't think I told you this last Wednesday. I had a zoom look. I haven't had any auditions in a long time. Last Wednesday. I had a zoom audition for a film being shot in Chicago. And of course, and now I'm on, I'm on hold for it. I'm on check avail for films in Chicago. And it's a big film. And it's, I'm like, what2 (27m 43s):If it's going to start filming, like on one, the one-year anniversary of the day you guys went there and then had to stay,1 (27m 50s):Well, the thing is, it starts filming Monday, but I oh yeah. For a month. But I, I, my part is super, super small. So I doubt I I'm thinking it's a one or two days shoot. If I book it and you know, the difference of, I mean, I feel like petrified of getting it because I'm, I'm just, I I'm, we're really, you know, that's my first go-to, but I also felt like it was the first time in an audition where I was like, you know, like, how can we talk about this on here? But like, how willing am I to treat myself? Like, shit, I'm not anymore as much. So like, no matter what happens if I, if I, you know, I'm not even sure I want to be an actor.1 (28m 36s):Right. So, so I, I have to get clear about that. I, so if I'm not really sure that this is my life's path, then, then, then the reason that I'm scared is definitely old stuff of being approved of and making a fool of myself and feeling like all is lost if I screw up, like, so that's what I'm working with. It's not so much that this is my dream. And I want so badly to be in this film that I'm so nervous. It is old stuff, which doesn't mean that it makes it easier, but it's just clear. So I'm getting clear. So I was like, all right, if that's the case, then how can I work with that? And I just, I just had, I was like, you know what?1 (29m 17s):I'm not going to pretend that I don't care because I do, but I'm also not going to, I just put my foot down in terms of beating, being, being cruel to myself, I put my foot down. I said, I am not, I am not willing to berate, belittle and hurt myself if I screw this up. Or if I don't get it, or if I do get it, I am not no longer willing. I'm just going to have to set some boundary with myself about my, my, how far am I willing to go with my, with my weirdness craziness and, and self abuse. And I just, so I didn't go there and now I'm on top of avail.1 (29m 59s):I mean, you know, it's like, it, I'm not saying they're totally related, but I'm just saying like, it makes sense to me.2 (30m 5s):Yeah. It makes sense. Because every time you go further and that's been the case like over the last year or the, we talked about this every time you you're like, I don't, I, you let it go. And all of a sudden,1 (30m 17s):Yeah. And like, no matter, I think the, for me, the freedom lies in no matter how badly I do or think I do, no matter how awful rotten, I may screw this up in my head, or even in real life screwed up because it happened, I am not willing to treat myself like a piece of shit. Like that's where I got to, because I thought that is the only thing I have control over really, really the evidence shows that I have control. And even that is questionable sometimes. But if I'm going to have control or ownership over anything, let it be about how I treat myself as I go through this experience or I'll still do it, or else not stop auditioning because this doesn't, this is not.1 (31m 7s):And so I thought, okay, okay, can I, can I, and I, and I, I really was like, I was like, breathe. You know, it's a zoom audition, it's weird breathe. And it was just me in casting. And then I just went right to check avail, but which is great, but two scenes and w and we'll see, but I think it just, it's all fodder for like, can I put, can I stop treating myself terribly well,2 (31m 32s):Well, you know, one thing for certain, you can never go wrong when that's your guiding principle, you can go wrong when your guiding principle is, will they like me? And is it okay at, am I good enough? You know, but you'll never go wrong with when you're trying to set when you're just trying to do something intentionally. I mean, that's kind of what we're talking about is like being extremely intentional, right. Instead of reactive about right. How do I want to wind my way through the situation? What do I want my, this is just a concept that I really am new to, what do I want out of the situation? How do I want to reflect back on how I conducted myself, forget about what I want them to do.2 (32m 13s):Right. Because that's what I've been focused on my whole life, the other person to do.1 (32m 17s):Right. I, I, how can I make, how can I, how can I yeah. Make this easier for them, better for them read their mind, do what they want me to do. And I'm like, oh my God, that, that, that not only forget, it's not, it can't happen because in my make-believe mind that that, that doesn't come into play, but it, it, it feels terrible. And it, and it increases my anxiety and depression because it's so, it's so unattainable. So at least if I, if, like you said, like, if I'm the, if I'm the problem, right. If I'm the problem, that means that I'm also inside of me is also the, when the solution, the success, you know, that, thank God.2 (33m 7s):Yeah. Yeah. Thank God. Yeah. That's the best news. So I have, I actually was just a couple of days ago thinking about you and your career paths and, and, and like the things that you have described to me, like you, you basically pursued acting because of your relationship with this other person who you wanted to emulate. And then you basically, you know, got the job as the, as the Hollywood assistant when somebody else came. I mean, it was all kind of, you know, not, maybe not that intentional.2 (33m 50s):And I remember having like, kind of a aha thought about it. I should have written it down because it's not occurring to me right now, but it was something about like, maybe it was just that the further she goes in figuring out the basic questions about what she really likes and what she really wants, this is going to be less and less of a thing. Like, you're the thing that you you've said a lot. Like maybe I should work at seven 11. Maybe I should work at this bakery. I don't know. There's something to it that I feel maybe it's that I feel you're really changing for yourself right now.2 (34m 35s):I see you approaching things with a lot more intentionality1 (34m 38s):And you know, what was so crazy is that I think this podcast for us is a way of actually looking at all that stuff. So like, even if the POC, I mean, I hope it goes, goes a global. And, but even if it's just for you and I to look at what the hell am I doing? Who am I, how, how can I make things better for myself? And thus be a better like kinder human probably for everybody else. Then that was all worth it. Because it's like, I could not keep going the way I was going and expect to be happy, or even at peace or even do something fun. Like I had to look at like, wait, wait, wait, what is underneath all this?1 (35m 20s):Like, I should just work at seven 11. And, and I, you know, and we say, this we've said this before, but like, I want to be clear, seven 11 is not the problem. I am the problem. Right? So like you work at seven 11. That's not what I'm saying. What I'm saying is that, like, for me, what using that is as an excuse and our tool to try to figure out like, okay, where do I belong? That's what it is like, where do I belong? Where do I want to belong? Where can I contribute? But also, like you say, like, what do I want, where do I want to belong?2 (35m 54s):It's actually the, are you my mother phenomenon? You know? But in this case regarding like, where's your place in the world instead of wandering around wondering like who's in charge of you or whatever, it's that it's, which actually they're both the same thing. They're both about belonging. Right. But instead of you making it about, I guess that's what it is just like, instead of you making about another person or another institution or another entity, you're figuring out where you're guiding your own self1 (36m 21s):And myself and like, yeah, that's just it. Where do I belong? And I don't know yet, but I I'm pretty sure it's not at the am PM. Do you know what I mean? I just don't know that that's going to do it for me.2 (36m 35s):No matter how good those hot dogs are, future, how,1 (36m 41s):How good the deal is, two for one veggie chips. You know what I mean? Like,2 (36m 48s):So then when I went to that amp, it was so like, it, no, it was like1 (36m 55s):Vibration whole. They it's like a club. It's like a club on the weekend.2 (37m 1s):That's what I felt like. I felt like I walked into a club with no music and the lights were really bright.1 (37m 8s):It's crazy. It's put the same vibe. Like, you're like, this is a whole scene here. There's a lot of back and forth.2 (37m 19s):Yeah. About that all the time at gas stations, by the way, because the people who work at gas stations, I think tend to be people who are in transition. And I just observed so much, like, I love the idea that at any place I am visiting in a transitory fashion, there's a whole entrenched, you know, rich, layered history and culture. And that I just don't have any idea about because how could I, it's fascinating to think about,1 (37m 54s):Well, that's why you're a good writer too. It's like you get in there and you can like observe and like create w like it's a whole world. That's there2 (38m 3s):To be curious. Fun to be1 (38m 4s):Curious about. Yeah.2 (38m 17s):Today on the podcast we talked to Amar derisory Amar is originally from Jordan, grew up in Michigan, got his BFA and his MFA, and is a fan of Shakespeare, has some great Shakespeare series that you can check out through his website. And we enjoy talking with him about what his lasting impressions are of attending theater school. So please enjoy. So Amar, congratulations. You survived theater3 (38m 54s):School. Thank you. Yes, I did. You2 (38m 57s):Survived it twice cause you got your BFA in Michigan, right? And then your MFA at DePaul. That's correct. So you must've been very committed to being an actor from high school or earlier.3 (39m 9s):Yes, that is correct. I think high school is where I got the bug. Some teacher encouraged me to be in the school play and I'm like, ah, no, no, no, you have a great personality. You can do a kid. You can do it. I'm like, all right. And as soon as I got on that stage, it was like, right there. It was2 (39m 30s):The feeling that you had.3 (39m 32s):It's it's, it's, it's it's excitement. And you get these, you know, these vibes like, oh my God, I'm doing something. This is fun. It's like an addiction. It really is. It's like anything else? I just, I just went crazy. I started eating the scenery because it was like, I'm enjoying, this could be another role. At one point I wanted to play like 5, 6, 7 roles, you know, because I just said, I want to do everything. It was that much excitement. So that's when I decided to really pursue this,2 (40m 4s):I think to do with, I don't know something about the way you just said that made me think you were set. You were keying into people are listening to me here. Was that something3 (40m 15s):People were looking at me, people were watching me. People were doing that. Yes. There to a certain degree. Yes. But you know, not to the point where I want attention, you know, like, look at me, look at me. But I wanted, I wanted to make people happy, laugh, cry, you know, do something. That was the thing. I think, I think what got me was when people reacted to your performance, people that then it's like, oh my God, I did that. I did that. And that is something that is just, you can't, you can't describe that feeling is, is, it's just, it's like a forest.1 (40m 52s):Something that you said that really sparked a memory of you for me was like that your you are, and look, this is not everyone. We're not a one-sided, but you are a people person. Like I remember that about you. Like, there are some people who just like people, I'm a people person too. But, and I, so I recognize that. And other people where I feel like from seeing you around in school and in plays, like you really had the ability to connect with a wide variety of different kinds of people. Do you know where that came from? If that's true, if you,3 (41m 31s):I identify with that. I, I make friends with people on the street, just I'll just say hi to anybody. You know, I that's just my nature, my personality. I believe if you say hi to someone, you, it just makes them feel better. I think, hi, how you doing? Oh, hi. Oh, kind of surprises them that, you know, I don't have any money to leave me alone. I think some people get, get pretty weird about it. When somebody like myself says hi, where it comes from. I can't tell you. I think it's just, I've always been an outgoing person since I was a kid. I remember my parents telling me that, you know, this kid is going to be something he likes to talk to people.3 (42m 16s):Just, I would just talk to people. Hi,2 (42m 20s):Do you have artists in your family?3 (42m 23s):No, I am the only artist. My brother, my brother's a doctor. My sister is a, is a teacher and an administrator at a school in Abu Dhabi and the Emirates. So I am the only performance.2 (42m 39s):It's always so interesting to think about. Like, of course, going back throughout your family's lineage, you're not the only artist you may have been. The only one who had the opportunity. Like this is the case for me, had the opportunity to pursue it. You know? Cause what I found after I decided that I really wanted to pursue this. It's like, oh, but then my aunt can kind of paint and this one can kind of write a little bit. It just feels like it's not something that they pursued for their, you know, for their regular career. But there it's a privilege, I guess that we, you know, got a chance in school and after to pursue it. And you had some great, you were in some great plays, Romeo and Juliet landscape of the body during the3 (43m 21s):That's right. Oh my God. I still have that picture of me and the golden matress that John Bridges, I'm going to send it to you. I got a whole bunch of pictures of sent to you today. So I was rummaging through the old photo albums and I found a whole bunch of DePaul pictures, but yeah. Yeah, that was, that was an interesting play. I landscape with the body. It was just a, a fun, a fun play, a fun.1 (43m 45s):Now did you, you said that you got the bug early on because the teacher sort of encouraged you then how did that grow into? Because I'm always interested in like, okay, so when you're in a play and I'm sure that, you know, you were magnificent and they, but how did it people loved you and you loved it, but how did that transform into like, I'm going to go to a conservatory because that place was, you know, DePaul, the conservatories are crazy. So how does,3 (44m 13s):Okay, this is a good story. I'm glad you asked this. No, I was, I was doing a play in Flint, Michigan and the lead actress, her and I were backstage and we were just chit chatting before our next it was, I think it was during intermission, but anyway, it doesn't matter. She actually, she goes, well, are you going to go to grad school? Are you going to continue your journey? And I said, I'm not sure. I thought I'd just stick around. Maybe do some theater around here. She goes, no, no, no, you should really go. There's this place called DePaul university. It's a great school. You should go and check it out. I said, really? I said, where's that Chicago? Okay. Well, you know, sure. I go to my, my professors that my undergrad school and they paid for the application fee.3 (44m 56s):I mailed it in. And I think within, I think within a few weeks I got my appointment to audition for the school. And it was in January, in the dead of winter, in Michigan, Nine feet of snow as we're driving to Chicago, I'm my friend and I, but yeah,2 (45m 20s):You applied. It was the only place you applied for grad school.3 (45m 24s):I applied at Purdue university as well. I got accepted at both, both places. The, and it was Purdue or Chicago, DePaul. But I think with Purdue, you're in the middle of nowhere. It's God's country out there. There's just the school. And that's it. Where you had the theater school in Chicago and a vibrant city. It was very infectious and scary at the same time. But that's when I met the infamous John Bridges. I thought I blew it to be totally honest with you. I thought I blew it. I did a, I did a classical and I did a contemporary, obviously Joe Slovak, John Bridges.3 (46m 4s):And I believe Betsy Hamilton where my, my auditioners, if you will. And I thought I did okay with the classical, the contemporary was kind of thing. I got an, I, you know, green to the business, didn't know how to actually present a monologue or, you know, my teachers back and undergraduate say, look, just put them together. Just stop and blah, blah, blah, or just, you know, they, you know, they told me what, what I had to do, but I just remember saying goodbye and thank you for the time. And Joe slow. It was, you know, okay, you got a good job, good job. You know, you have a great journey back home. And I said, okay. And my friend goes, how did it go?3 (46m 46s):And I'm like, ah, forget it. I'm going to Purdue. I'm going to Purdue. And then, and then shoot, I auditioned on a Saturday in January. I get the letter on a Tuesday. And I remember my friend goes, Hey, you got this letter from DePaul. Why don't you open it? I said, oh, it's BS. They're just telling me they're not going to accept me. Look, I'm going to open it. I was about to rip it. And I said, oh, but it just opened it. And I'm like, oh yeah, let me read it to you. You know, I'm going to decline. You have been formally accepted.2 (47m 20s):Oh my God, that's amazing. That's a side note. Do you guys know that in today's day and age, when kids get their acceptance, it's email obviously. And then a lot of schools or maybe even most schools when they open the email, if they got accepted, it's a confetti graphic. So like they know as soon as they open it, if there's confetti, that is so it's so wild, right? Like the things that they could never imagine having to wait in a letter to come in the mail,3 (47m 52s):But2 (47m 52s):You did BFA. So why, why are you saying you kind of were green? You knew about,3 (48m 0s):I mean, I knew about acting it's I, I didn't know the, the, what we call the business affairs of acting the mechanics of acting, I guess I think, you know, we all experienced this. I'm sure guilty is charged. You know, when you're young or you're an actor, you really don't pay attention to a lot of things. You just want to, you know, you want to act, you want to do a performance. You want to do the best you can, of course. But then you also want to party afterwards and do all the things that young people do. And I, and I think I was talking to one of my fellow actors the other day and he asked me if you were to go back to grad school, what would you change? Or what would you, what would have helped you? And I said, have a class that teaches the business of acting and okay, these actors are going into Hollywood.3 (48m 47s):They're going to New York. They're going, whatever, teach them the basics of what the business of acting is. They got to know what a contract looks like. They got to know what business affairs mean. They got to know all this terminology. They got to know all that stuff. If I had known that that would have been a great tool for me coming to LA, coming to LA, I was green as green as a Shamrock, you know, just green. And I had to learn the hard way1 (49m 10s):And we'll get back to the LA part, but I'm not so curious about, okay, so you get into DePaul and then when, and usually being zest this, but I'll ask this, like when you get there, how did it match up to what you were thinking? Were you like, what the hell is going on? Why am I rolling on the floor to music or what?3 (49m 29s):I had no idea what was going on. And that I think scared, you know, on a side note, Chicago scared me. I was homesick for quite a bit of time before school started, I got to, I moved to Chicago, I think three weeks before school started. So there was three weeks where I did not know anybody did not know. I didn't know. Oh, I was in bad shape. And thank God for friends and family. Of course, you know, they call and man, you sound depressed, which is that dude. I'm by myself in Chicago. I don't know anybody. I don't know the city. It's a big city. It's like Flint times 20.3 (50m 9s):It's huge. But, but I think I, to answer your question about the school when the first day of school, wow. What up Betsy Hamilton's class. I'm like buoyancy. And I'm like, what the hell is she doing this buoyancy famously I ever done? And then it clicked it. Then I'm like, okay, I know what she's doing. All right. Okay. Joel, slow acting class. Woo. You can't do that. Okay. You got to do it this way. Okay. This little guy is running around this class and he inspired me.3 (50m 55s):I'm like, this is beautiful. This man in his seventies is running around like his, a guy in his twenties. He loves acting grub. Kowski all that stuff. And he was amazing, but4 (51m 8s):We didn't have him. So he's he was real. Hands-on3 (51m 11s):Like hands-on he was, I mean, I, I won the lottery with Joe slower. N not, not to say anything negative about Jim ocelot or anything like that, but he was just, he was on hands. And he really gave you when he gave you a note, he gave you a note. Okay. You know, he's like Amar, okay. Your legs. I don't know why your feet are doing that on the chair. It's like, it's not, it's not, that's an ism of yours. We gotta, you gotta, yeah. That's kinda like your feet, your feet, your body, your, your, your body is your instrument. And, you know, got to learn all this stuff.3 (51m 52s):And it's just woo. Graduate school. This is graduate school. So, yeah, that was a, a couple of experiences. I'm trying to think.1 (52m 2s):Did you feel like you fit in? Did you, did you, what was your, what was your vibe like there?3 (52m 10s):Unfortunately, my violet started to change in year two. That's when I started to feel, not that things weren't clicking for me or anything like that, but it just seemed like favorites started to appear. Oh, okay. You know, it's like, it happens. It's not something that, you know, it's done intentionally. It just happens. But if I, if you guys remember Eric Hayes, Eric, Michael Hayes,4 (52m 43s):Isabel. I haven't3 (52m 44s):Thought he was in Trojan women. I think he1 (52m 50s):Was like, yes, yes, yes, yes. So3 (52m 52s):He became a seminar. Yeah. Him and I don't know him and I beat we're we're unofficially the outcasts of the graduate class more or less. We weren't, we were not that, not that we were mistreated or anything. I'm not saying that we were mistreated by it just, it just seemed like we were known as the two actors that really didn't take things seriously. And I think that's a fallacy because I think I was taking it very seriously. I was just bored at times. I wanted to act, I didn't want to sit in a classroom all day and just sit. I wanted perform. I think, I think I understand the classroom format where you sit down, you watch your colleagues do their scenes, but I was getting fidgety, fidgeting, bored, bored.3 (53m 39s):And to the point where you dread going to school, it was like, oh, I've got to go to acting class and sit there for two and a half hours. And watch people act, you know, which I get. And again, that didn't sound right coming out. But I mean, it's just, I loved, I loved all my classmates. I loved all my classmates. I think from Derek smart to Eric Hayes, the niece Odom, Heather Ireland to name a few, you know, they, they were fantastic. Pat. Tiedemann Kendra. I mean, and one of my, let me aside. No, one of my favorite, favorite times on DePaul was with you. Gina.3 (54m 19s):Do you remember you? And I started a film. I, I did.2 (54m 23s):Oh, say what3 (54m 27s):You guys remember bill Burnett. The voice in nucleus. Okay. So for our, for my final exam, I wanted to film a short film about quitting smoking. And2 (54m 38s):Coming back to me, wait a minute,3 (54m 40s):You were asking me, I had to, I rented a camera from the video department on the campus and I walked into the lobby of the theater school and you were there and it's like, I need to shoot a scene. It's like, oh, let me be in it. And I said, okay, we'll just improv. We'll just talk about quitting. So we set the camera and you and I sat in the lobby and we filmed it and we did it. I think I still have it. I'll find it for you in 1994.2 (55m 7s):I have to tell you something, because I know you haven't been able to listen to the podcast because our website had a broken link. Okay. But what, what I should tell you is that boss and I have huge memory gaps about our time. There are many things we do not remember.3 (55m 28s):What2 (55m 29s):What's kind of weird is I sort of remembered this film that you really are hearing about it. Yeah. I mean, I believe you, I believe both of you. Okay. How exciting, you know, why I would really love that is because just last week I was saying to boss, wouldn't you like the opera? Because nothing was recorded. Really? Not even our showcase or if it was, it's not something I ever saw. No. Wouldn't you like to go back and just watch yourself? Because now we've spent basically a year and a half fully immersed. We have talked to 55 people about what their theater school experiences.2 (56m 9s):So we, we are getting back on board with what it was and we're slipping, you know, different people fill in like little bit of blanks. But now I like, now I'm just so curious about, you know, what, what, what was the experience of what was I like at that time? And a lot of people don't remember us, so we haven't really gotten this feedback from3 (56m 29s):Yeah. I mean, I remember boss. I remember all you guys. I do remember a lot of, and there's a lot of people I don't remember. I mean, I think when I was on your website the other day, you know, trying to figure out what you're like and it, which is congratulations to the both of you. I think it's awesome. I saw Tate Smith. I saw a picture of Pete Smith and I completely Like that. It was stuff like that. You know, you running into people that wow, amazing. I'm sorry. Go ahead. I interrupted you.1 (56m 59s):No, no, no. I was just going to ask, like, what was your, okay, so, so year two, you started getting itchy and like, but how did you feel? We talk a lot about like casting. How did you feel about your casting in shows? Which most people do? Like, there's been like one person that we've talked to. That was like, I loved my casting, but everyone else is like, I fucking hate it.3 (57m 23s):Nope. I haven't hated it. I hated it. And again, like I said, it happens. I think, I think a lot of the directors, the professors who are directing and all that stuff were just picking their favorites. They're not, if we're going to be in a learning environment, then you, you should take a risk with me, with somebody else with, with Heather. I think nobody was taking any risks. And everyone's like, Hey, I gotta put on a show and it's gotta be the best show I possibly can. And I'm going to use the best actors or that, you know, my opinion, the best actors. And it's like, you know, you know, if you're, you're not preparing us for the real world, you know, if you're going to do this, you know, this blind casting, whatever I thought I thought, Hey, it's a learning. I'm sure. I'm sure one of them, I'm sure Jim Ossoff will cast me.3 (58m 3s):Never did Joe slow cast me, you know, and his journey of the fifth horse. It was a great experience for me. That's when you learn, I didn't want to be the lead role. I want to learn. I want to learn, teach me, teach me what it like to perform on a stage that would typically be a stage from new in New York or a main stage in Chicago. That's where we got to learn. Right? Yeah.2 (58m 29s):That's another thing that we've really uncovered here and it, by the way, it makes perfect sense. I'm really not maligning anybody, but that the professors, you know they, they were also trying to express their own artistic desires through the projects that they were casting. And I'm sure nine times out of 10, they got carried away with their own ego about what they wanted to like, actually, we just heard this story from the episode that's airing today with Stephen Davis.3 (58m 58s):Oh, wow. Yeah.2 (59m 1s):That's a great episode. You listened to it. He re he begged the theater school to do Shakespeare. He begged them to do Romeo and Juliet, which they did. Yep. He, he really wanted to be Romeo. He didn't get cast. And he was told if I had cast you, I would had to gone with my fourth choice for Juliet of the height, because Karen mold is very tall. That's a perfect example of something that should be okay in theater school. I understand you don't want to do it when you're charging $400 a ticket on Broadway.1 (59m 38s):We're in a film where the camera's going to be jacked up, but like, but just cast. And sometimes, and sometimes I would think that, and maybe they do it now. Like sometimes you would say, why not? No. Cause it's obvious when someone wants a rule, right? So whoever wants this rule so badly, for whatever reason, they've never been cast and whatever, give them the role, let them do the role. Like maybe it's, maybe it's not, it's a long shot, but that's what school's about is long shots and learning. Right? It's like, let, let the person do this. You know, they're dying to play Romeo. Just let them play Romeo.1 (1h 0m 19s):Yeah.3 (1h 0m 19s):Yeah. Okay. And excuse me, the, if, if, if you don't mind, you know, now that you guys have you, of course, but I'm just saying the play was set in the middle east.2 (1h 0m 31s):Right. Very3 (1h 0m 32s):Last time I checked I'm Jordanian.2 (1h 0m 35s):Right?3 (1h 0m 36s):The play Romeo Lord Capulet he was Jewish. I'm sorry. He was the Jewish character, but yeah, I get it. I totally get it. I totally get it. And I agree with Steven on this one, because it just seemed like, it seemed like we are in a learning environment and let's learn. And if you're going to, if you're going to just cast people because whatever, then, then what's the point of going to the, to the fricking school and spending, spending $16,000 a year. I don't know what it is today, but1 (1h 1m 10s):It's like 48 or some craziness3 (1h 1m 13s):For paying student loans for three years, three years of, you know, every now and then some BS. Okay. Other than that, you know, the two best teachers that I had over there, arguably as Dr. Bella and Joe slower. And I think because they come from, you know, such interesting backgrounds, you know, Joe slug being Polish, you know, Bella, it can be in a Russian Jewish woman. Oh, I got a lot of stories while her, oh my God.1 (1h 1m 43s):She did she help you? Do you feel like she helped you as a teacher?3 (1h 1m 47s):Oh, she was. She, she, she, I am in her debt, you know, when it comes to acting and stuff like that. I think, I think she finally, I think she was the one that I finally, I realized what it's like to feel the, you know, like with the apple and, you know, I didn't know. It's like the Pandora box thing that she was talking about. And then it just like a light bulb over my head. It's like, oh my God, the feel what it's like to be in winter, you know, even though you're on the stage and it's hot, you gotta like, as if it's 40 below zero, she really, that, that, that, that technique, that acting technique was just incredible.3 (1h 2m 28s):I am forever in her dad and she is awesome. She's an automation rest in peace. And I, a couple of great stories about her is one that when she would like to meet her students before class, so we will walk into her office and talk and I'm sitting there in the office, she's looking at the hair. She goes, okay. Oh yeah, that doesn't sound English. And I said, oh, well, it's, it's Jordanian. I'm from the police. It's Jordanian. She goes, oh, well, you know, I'm Jewish. And I remember talking to my dad, I said, dad, I, I have to talk to this Jewish professor.3 (1h 3m 9s):You just say we're cousins. Okay. Because we are just say that don't rock the boat. Okay. So when she said they're doing, you know, I'm Jewish. And I said, well, well, yeah, I do. I do. But you know, being Jordanian and you being Jewish, you know, we're, we're practically cousins. So, you know, it's great, right. Without a drop of a dime, she goes, well, we might be cousins over, not exactly kissing cousins.2 (1h 3m 38s):Oh, that's hilarious. By the way, in case you don't know, I might have mentioned this on the podcast. Once before there exists on the internet, a Hastick interview with Joseph Loic and Bella it kin, okay. Was it conducted by studs, Terkel? It might've been, or some radio project. And the two of them talking about their approaches to acting and to teaching acting is really, really good. Yeah. You got to check it out. Right. So she really helped me. W we didn't, neither one of us had either one of those teachers, unfortunately, but we love,3 (1h 4m 13s):She, she was great. And I would give her ride home, poor thing. You know, she, you know, her husband, Frank was very ill at the time and she was like, oh, muck. And you're giving me a ride home. And I'm like, yes. Yes. Ma'am. And I was like, oh, you'll cause kind of a mess there. What'd you just get in the car.2 (1h 4m 34s):We know you had a car. That's K that's it wasn't that useful for people in school? Did you, and you messed up, I guess all the MFA's probably lived in apartments or was there any dorm living for MFS?3 (1h 4m 45s):No, no, no. Don't limit for MFA. So we had to live in apartments and my first apartment was a studio. And then I think the second year I moved in with, with Eric, from school and then we had a former student. I don't know if you remember John Soldani by any chance familiar. He was first year grad. And then I think he was cut from the program after the first year, but he came back to Chicago. So we were roomies. And then I met my girlfriend who was also a student at DePaul, Alicia hall. Right. So we, we were together. So we moved in together, I think, mid third year, something like that.3 (1h 5m 29s):I'm not sure, but yeah. And then I stayed in Chicago after graduation. I just decided to stay in Chicago and did get quite a bit of theater in Chicago and then decided to do the LA thing. And,1 (1h 5m 41s):Okay. So, so I just have a question about what was your experience like of the warning system and the cutting system where you weren't?3 (1h 5m 49s):Oh, good question. Good question. Oh, I'm glad you brought that up. I think it's, I think it took the attention away from the program because I think all the students were more concerned about the warning, getting warned and getting caught than anything, and that affected their performance in class and it affected their performance on stage my opinion. I remember some friends of mine who were just scared and I admit I was very, very nervous, but when I didn't get warned, then all of a sudden I was able to concentrate on school. I was like classes where the people that were warned, all they can think about what I can do to not get kicked out of the class.3 (1h 6m 31s):And then next thing you know, it just, it just really, really was detrimental to their performance in my opinion.2 (1h 6m 38s):But it took the focus3 (1h 6m 40s):Away. Oh yeah. Never worn. I was the only, I was the only male that wasn't warrant. All the male actors were warned except for me. And we ended up having eight graduate students, three men and five women, which I mean Derek smart, Eric Hayes and myself, and then the five women, Denise home, Heather Ireland, pat Tiedemann Kendra. I forgot her last name. Thank you. And Alicia, Alicia, Alicia was in the other class. Lisa was in the other, but I remembered you guys remember a teacher named Susan Lee.2 (1h 7m 24s):Her name has come up at times on this podcast. Yes,3 (1h 7m 30s):She was my advisor. She was the one that told me whether I was warned or not, or kicked out or not. And she said the most procurator thing. And I'm not sure if it was from the professors, but she said, well, you're not cut. You're not warned. We just don't know what to do with you. I just looked at her. What do you mean by that? Well, I mean, you're, you're, you know, I don't remember the conversation.1 (1h 7m 55s):Did she say that she raised, she say something about being a, from the middle east or3 (1h 8m 3s):Yeah, something like that. And I said, well, why don't you, why don't you and your professors just ask me and find out what you can do. Right? I mean, just I'm middle Eastern doesn't mean, I don't know how to act girl. You there.1 (1h 8m 23s):Wait a minute. So wait a minute.3 (1h 8m 25s):There's more than one professor that kind of, oh, I'm sure. I'm sure I'm not going to mention any names, but2 (1h 8m 32s):There was quite a few.1 (1h 8m 35s):Yeah. Right? To say that, that, that being from the middle east, my guesses, people were assholes about it. Like right. Like racist, racist, assholes.3 (1h 8m 50s):I mean, and that's what was going to be NASA, regardless of what race you are. So, you know, you're going to be an asshole. You're going to be an asshole. If you are a mean person, you are a mean person. It has nothing to do with your gender, your culture, where you come from, you're you, if you're a mean person, you're a mean person having said that there was quite a few people that said some things to me while I was in school, which was very offensive. But what do you want me to do? Fight every person. That's some kind of, you know, I was called many things. I was called camel jockey. I was called by students. Oh, somebody students. Yeah. Mostly by students. You know, I was called no, no, no. It's okay.3 (1h 9m 31s):Hey, that's you know, you, you grow from it. There was, there was one person that called me a word. I don't think I can say it on this podcast, but it's a, it's like, whoa.2 (1h 9m 42s):Well, well, we've heard so much about from every alum of color that we've talked to, is this thing that you're describing of maybe they even got selected for the program with the idea, oh, you know, we don't have anybody who looks like this in our program, but then it became, we can,1 (1h 10m 2s):We don't have any money.2 (1h 10m 3s):We can only find a role for that person. If it's clearly identified in the text that that person is that ethnicity. Meanwhile, all the white actors could be up for any role. Right. That, that was sort of the default. Like if you're white, then you can play anything. But if you're not white, then you, then you have to play a role that's written for whatever your ethnicity is.3 (1h 10m 27s):I agree with that. And yeah. And I think, I think Christina dare kind of broke the window on that with Romeo and Juliet, by casting Leonard Roberts as Romeo, you know, an African-American man. And he was great in the role. He was great. Absolutely. You know, she passed me as, you know, as a Jewish man, you know, even though I'm there, I like that. I I'm playing against type. This is, these are the rules that I would like to be challenged with. And unfortunately I wasn't challenged with over there. And I think the school to your saying, Gina, I think the school was just kinda like, eh, let's just bring this middle Eastern guy. See what happens. Let's get this African-American person. Let's see what happens. Let's get this Indian person. Let's see what happens. And nothing happened, nothing happened.3 (1h 11m 8s):And, and by the third year, by the third year, I was just, I was done. I was done. After, after Shakespeare, Susan Lee, I was done. I was done. She, she was a hard teacher. She was a hard teacher to deal with both academically. And you know, personally it's just, just was hard. It was hard to deal with her. I'm not, I know Bobby, some students have some harsher words for her, but again, I was going back to what I said earlier, Eric and I were pretty much marked by her that we were not serious about Shakespeare.3 (1h 11m 48s):And I was very serious about it. I just wanted, I remember students coming up to me, they tried to avoid being partners with us. And then I had one partner telling me, Hey, you better not fool around or do this. You know, you gotta be serious. I said, what the hell is wrong with you? And then when they find out the real me, and then it's like, wow, that's totally different than what I'm hearing about you. And I'm like,2 (1h 12m 11s):Yeah, this is serious. Is my lasting impression of you. I would never have said that you were anything but very serious.3 (1h 12m 21s):I appreciate that. I really do. I appreciate that. I

Shelly hangs with Myc again to dive into the mind of William Leonard Pickard. Myc calls him an ENIGMA-defined as 'a person or thing that is mysterious, puzzling, or difficult to understand'. I would have to agree. In the middle of reading this epic memoir that is at times magical realism and often an historical reference, I heard him speak at the inaugural Enthoefest. He was the most present soft spoken world traveling master chemist recently released from a life prison sentence psychonaut that I have ever met. His journey takes him out of prison to the monastery to Harvard to the sometimes dark and terrible and sometimes healing and beautiful drug behavior and policy that effects it all over the world and back to the largest LSD production lab bust in history. Well, it isn't boring. Also, reading someone's story through their own beautifully elevated consciousness and understanding is just so lovely.

Message by Pastor Tim Somers on Friday, Oct 22nd, 2021 at MYC

Message by Pastor Tim Somers on Thursday, Oct 21st, 2021 at MYC

Message by Pastor Peter Reeves on Friday, Oct 22nd, 2021 at MYC

In part one of this two-part ASCO Education Podcast episode, Dr. Sonali Smith (University of Chicago Medicine) and Dr. Paolo Strati (MD Anderson Cancer Center) discuss the application of recently approved therapies for diffuse large B-cell lymphoma through examination of challenging patient cases. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 10/20/21   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] SONALI SMITH: Hello, and welcome to this episode of the ASCO Education Podcast highlighting new therapies for lymphoma. My name is Dr. Sonali Smith, and I'm a hematologist and medical oncologist specializing in lymphoma and clinical investigation in lymphoma. I'm also the Elwood V. Jensen Professor and chief of the hematology/oncology section at the University of Chicago, and very excited to be joined by my colleague, Dr. Paolo Strati. PAOLO STRATI: Good morning to everybody. My name is Paolo Strati. I'm a hematologist and medical oncologist and an assistant professor in the Department of Lymphoma/Myeloma, and in the Department of Translational Molecular Pathology at MD Anderson Cancer Center, Houston, Texas. And I'm also the clinical director for the Lymphma Tissue Bank. In part one of this podcast episode, we will discuss the adoption of recently approved therapies for diffuse large B-cell lymphoma, such as selinexor, tafasitamab, Liso-Cel, and Lonca-T. These therapies have transformed care for patients with this disease. And we'll start our conversation today with a patient case. SONALI SMITH: Great. Well, I'll go ahead and present a patient to you, Paulo. So this is a 78-year-old man with diffuse large B-cell lymphoma that is the germinal center-derived subtype. It is not double expressor, it is not double-hit. He has advanced stage disease with a high IPI, as well as the high CNS IPI. Luckily, his performance status is zero and he has no significant comorbidities or other health conditions. He received frontline dose-adjusted EPOC-R with intrathecal methotrexate for six cycles. But at the end, he had a partial remission. So how do you select your salvage therapy in this situation? Are you concerned about using agents targeting CD19 in the second line, given the potential need to use anti-CD19 cellular therapy, or CAR-T in the third line? PAOLO STRATI: This is a very interesting and unfortunately not uncommon case. And thank you, Sonali, for asking these very important questions. Technically, a platinum-based regimen followed by autologous transplant will be a standard answer and may be feasible. Because as you mentioned, this patient has a good performance status and non-meaningful comorbid health conditions. However, patients who are refractory to a frontline anthracycline-based regimen, such as in this case, with achievement only of partial remission at the end of frontline dose-adjusted EPOC, can potentially experience a suboptimal outcome following the standard approach with a platinum-based second line regimen. And as such, alternative strategies may be needed. To this regard, the combination of tafasitamab that, as you know, is a monoclonal antibody targeting CD19, and lenalidomide, an oral immunomodulatory agent, a combination which is currently approved by the FDA in the United States as a standard second line option for transplant ineligible patients, would be a great option in this case. Data from the three year follow-up of the phase II study that has brought to the FDA approval this combination, the L-MIND had been recently presented and have showed the complete remission rate of 40% and immediate duration of response of 44 months, including patients who received this regimen as a third line or beyond. So there is, of course, a biological concern by targeting CD19 in second line. These may potentially impact a third line use of an autologous anti-CD19 CAR-T, because CD19 downregulation may potentially be a mechanism of escape to tafasitamab. And recent data has shown the CD19 levels are strongly associated with the efficacy of CAR-T cell therapy in patients with large B-cell lymphoma. Small retrospective studies have shown that autologous anti-CD19 CAR-T can be safely and effectively used after antibodies or antibody drug conjugate targeting CD19. But we need a significantly larger and prospective data, including serial tissue biopsy in these patients before considering this combination as a standard practice in patients for whom we plan to use CAR-T as a third line. Until then, I would be cautious in using second line tafasitamab in patients, again, for whom there is a potential plan for anti-CD19 autologous CAR-T in third line. And if necessary, limited to very selective cases. Finally, recent press releases have anticipated the two autologous anti-CD19 CAR-T products, Axi-Cel and Liso-Cel, are superior to autologous settings transplanted in second line. And so in the near future, CAR-T cell therapy may become a standard second line option. And that would be an ideal option in primary chemorefractory patients as the case that you presented here. SONALI SMITH: Yeah, I agree. There are a tremendous number of options. And having anti-CD19 products as well as autologous stem cell transplant, the sequencing will be an evolution. So going back to this patient, he received tafasitamab and lenalidomide for two cycles with no significant toxicity, but unfortunately, he had further progression after two cycles based on a PET/CT scan. So what are your next steps? Would you move directly to an autologous anti-CD19 CAR-T cell therapy now? Would you re-biopsy before that? And how would you select among the three available CAR-T products? PAOLO STRATI: These are not easy questions, particularly the selection of one out of three available CAR-T products. As you said, there are currently three autologous anti-CD19 CAR-T products approved by the FDA in the United States for the treatment of large B-cell lymphoma in third line or beyond. And these are Axi-Cel, Tisa-Cel, and Liso-Cel. For all of them, the best outcome is observed for patients who have a low turmor burden at time of CAR-T infusion. And they need to either select patients with no bulky disease or to decrease it through bridging therapy. And as we define bridging therapy given between leukapharesis and CAR-T infusion. Unfortunately, there is currently no standard bridging therapy and all FDA products approved in third line can potentially be used in this specific scenario that you described, including polatuzumab with bendamustine/rituximab, selinexor, and Lonca-T, of course, beyond tafasitamab and len that has already been used in this case. Of course, when selecting a bridging therapy, there are many disease-related and patient-related factors to take into consideration, including the need to preserve the host immune microenvironment that we all know is crucial for the subsequent activity of CAR-T cells. And also, we need to give into consideration the need to preserve as much as possible, as we discussed previously, in CD19 expression. To this regard, and going back to one of your questions, I strongly recommend to re-biopsy patients if any bridging therapy is used between bridging therapy and CAR-T infusion in order to document CD19 expression before CAR-T infusion. When it comes to CAR-T product selection, as I said, it's a really difficult decision to do. And we don't have at this time randomized trials in third line. And as such, the decision is really left to the treating physician based on multiple factors. But all of the limitations of inter-study comparison, efficacy seems to be pretty much the same for the two products, maybe slightly higher based on the recent second line data. But Axi-Cel and Liso-Cel as compared to Tisa-Cel, and also as suggested by recent press release. However, due to the fact that Liso-Cel and Tisa-Cel have less potent co-stimulatory domain for 1BB instead of CD28, the rate of CRS and ICANS, the two main toxicities associated with CAR-T cell therapy, is usually lower with this to the point that some centers are able to infuse them in the outpatient setting, whereas Axi-Cel is almost always infused in the inpatient setting so the toxicity can be monitored more closely. So with older patients or those who have comorbid health condition, Tisa-Cel and Liso-Cel may be a safer option, though there's a lot of research going on trying to mitigate toxicities associated with Axi-Cel. Finally, it's important to keep in mind manufacturing time. Axi-Cel is manufactured in an average of 17 days, whereas Tisa-Cel and Liso-Cel take typically longer than three to four weeks. This can be itself a determining factor, particularly for patients who are quickly progressing and where immediate treatment is needed. SONALI SMITH: Yeah, I agree. I think there are going to be many patient product and disease-based factors that will impact both the effectiveness as well as the toxicity. And you did a really great job of explaining the role of the co-stimulatory domain potentially in some of that, as well as all of the products that are out there. It's definitely a complicated area. Going back to our patient, so he did undergo leukapharesis for Liso-Cel and received third line polatuzumab and rituximab without bendamustine. The restaging PET/CT after two cycles showed a PR with a significant decrease in tumor burden, and repeated biopsy showed high expression of CD19 by flow cytometry. He then proceeded with Liso-Cel, which was relatively well tolerated. There was only grade 1 cytokine release syndrome and no ICANS, so no neurotoxicity. And his day 30 PET/CT showed a complete remission. Unfortunately, the 90 day PET/CT showed progression. So Dr. Strati what is the outcome for patients who relapse after CAR-T? Do you recommend to re-biopsy? And what are the efficacy data for FDA approved agents for these patients? And I know this is a long question, but is there any role for repeated CAR-T or allogeneic transplant now? PAOLO STRATI: Unfortunately, currently, the outcome of patients with large B-cell lymphoma relapse or progress after autologous anti-CD19 CAR-T is suboptimal, with a life expectancy, unfortunately, shorter than six months. Hence, the need to be creative and customize treatment based on biological data. To this regard, I think it's crucial to repeat a tissue biopsy to guide subsequent therapy. As mentioned previously, there are currently four products approved by the FDA for patients with large B-cell lymphoma in third line and beyond. Two of these target CD19, tafasitamab plus lenalidomide and Lonca-T One targets CD79B, polatuzumab combined with bendamustine and rituximab. And one is an SPO1 inhibitor, selinexor. While we have no data for selinexor in patients who relapse or progress after CAR-T cell therapy, limited prospective data showed that a progression-free survival in the order of weeks is usually observed for patients who receive polatuzumab with or without bendamustine and rituximab after CAR-T cell therapy. So I would not recommend that. However, there's some interesting activity in the post-CAR-T setting for Lonca-T and for tafasitamab/len is limited to patients who still express CD19 in time of relapse. And of course, it needs to be largely and prospectively further investigated before becoming a standard approach for patients who relapse or progress after CAR-T cell therapy. When it comes to cellular therapy, repeated anti-CD19 CAR-T infusion is not shown to be successful in the original registration studies. So it is not currently something that I would recommend and is not definitely a common practice. And very limited retrospective studies have shown the use of allogeneic stem cell transplants in the post-CAR-T setting may be associated with quite elevated treatment-related mortality. So I don't suggest this as a standard practice in large B-cell lymphoma at this time. This is different from B acute lymphoblastic leukemia, where instead, allogeneic stem cell transplant is becoming progressively a standard approach. And we definitely need more data before using this consistently. While we strive to identify the optimal cell batch therapy for large B-cell lymphoma patients who relapse or progress after CAR-T cell therapy. I think the priority should be given to clinical trials, including CAR-T targeting molecules other than CD19, such as CD20, CD22, CD79B, allogeneic CAR-T there are immediately available, so without the need to wait for manufacturing times. And K-CAR, that may be less toxic than CAR-T and other non-cellular therapy biological agents. So definitely, clinical trials are, at this time, the best approach in patients who relapse after CAR-T cell therapy, as the case that you described. SONALI SMITH: Thank you Dr. Strati. As an update, this patient had repeated biopsy showing a CD19 positive relapse. He consented for a clinical trial with a novel NK-CAR targeting CD19, achieving CR which is still ongoing at nine months. And this case really does represent some of the most exciting advances that we've had for this disease for patients who can tolerate aggressive therapies and have access to clinical trials. PAOLO STRATI: Dr. Smith, I'd like to hear your opinion about another patient with diffuse large B-cell lymphoma. This patient is an 81-year-old man with a history of coronary artery disease and well-controlled diabetes mellitus, who noticed a right cervical lymph node while shaving that seemed to have popped up. He was evaluated by his primary care physician and given a course of antimicrobials. 10 days later, the lymphoma seems to be enlarging and he is referred to ENT pharyngeal biopsy. The specimen is small but shows follicular lymphoma in a portion of the sample. However, there is also concern for larger cells and possible transformation. The patient is also beginning to note night sweats and a decreased appetite. And labs are notable for elevated LDH, 500, and thrombocytopenia with a platelet count of 110. So Dr. Smith, in your opinion, is this specimen sufficient to start treatment? Or should treatment be delayed to get a larger and maybe excisional biopsy? SONALI SMITH: Yeah, thank you for this question. I think this is a challenge we have in the clinic all the time, which is what is a sufficient biopsy specimen to make a diagnosis that allows us to subtype lymphoma? As we know, every lymphoma subtype, the treatment is really guided by the histology and not so much the stage or some other factors. So having a needle biopsy is unfortunately often insufficient. In this case, we have a very strong concern for a possible transformation. And as we know, both follicular lymphoma and diffuse large B-cell lymphoma can mark very similarly when it comes to immunophenotype. Certainly, the germinal center type of diffuse large B-cell lymphoma or any transformed follicular lymphoma will be CD20 positive, CD10 positive, and it really requires architecture to be able to tell whether or not there are sheets of large cells. So the ideal outcome for this patient would be to have a biopsy that is done promptly that allows us not only to confirm whether or not there is histologic evidence of transformation, but also to conduct FISH studies to determine if there's acquisition of a MYC rearrangement. At its core, all follicular lymphoma patients essentially have a transformation of 14;18, leading to BCL2 rearrangement and BCL2 overexpression. During the transformation process, there can be an acquisition of a MYC rearrangement, which would then make this a double-hit lymphoma and certainly has a much worse prognosis and may also prompt a change in treatment if the patient can tolerate more intensive therapy. So my recommendation would be to have a biopsy. Now one other aspect is that sometimes, we don't really have the time to proceed with a biopsy, or the lymph node may be in an inaccessible area. And in that case, there are some other criteria that we can use to assume that somebody has a transformation. Symptoms such as profound B symptoms and elevated LDH, and sometimes, a PET scan with multiple areas of very high avidity, can lead you to feel or suggest that this person has a transformation. There is some controversy over the use of PET and we know it does not confirm a diagnosis of transformation. But in my opinion, this is very suggestive if there are many areas of high SUV. PAOLO STRATI: Thank you, Dr. Smith. I agree completely about the importance, when time allows, to perform either a larger core biopsy or an excisional biopsy, because as you very well-outlined, this has not just a mere diagnostic purpose, but can meaningfully affect treatment planning for patients. And actually, in this case, as you suggested, the patient eventually had multiple core biopsy that showed transformed follicular lymphoma with very evident areas of diffuse large B-cell lymphoma. FISH, as expected for follicular lymphoma, was positive for translocation for TN18, but luckily negative for MYC rearrangement. So fortunately, we didn't have to deal with a double-hit lymphoma. The remainder of his staging showed he had diffuse lymphadenopathy. And PET scan, as you mentioned, has a controversial role in the diagnosis of transformation. So there's some areas that had high avidity with an uptake with an SUV of 1215, whereas other areas were less intense with SUV 618. And usually, heterogeneity in SUV actually helps further supporting diagnosis or transformation. While meta-maps showed follicular lymphoma, no large cells. So movement was isolated in the B-cell lymphoma. So Dr. Smith, at this point, based on the provided information, what's your treatment approach in this older patient and also a patient with comorbid health conditions, but with diffuse large B-cell lymphoma? SONALI SMITH: Yes. The goal of treating any aggressive lymphoma is to obtain remission, and if the remission lasts, to hopefully offer cure to the patient. And when somebody has a transformed lymphoma, of course, there is a dual concern, which is that the aggressive component can potentially be put into remission in a durable way achieving cure. But the indolent component will always need to be monitored, although hopefully, will not be life threatening the way the aggressive component can be. Treating an octogenarian is really challenging, particularly due to comorbidities in this age group and the potential toxicity of chemotherapy. So the standard of care for diffuse large B-cell lymphoma is anthracycline-based chemotherapy. But this, of course, can have significant toxicity in older patients. And in addition, the vincristine can aggravate neuropathy. And I've personally found that the high dose steroids that are part of CHOP can also cause toxicity in older patients and patients who are frail. So unfortunately, the literature is somewhat sparse. But we do have several data sets that can guide management in this particular patient situation. The French published, over a decade ago, the development of R mini CHOP, that includes an attenuated dose of cyclophosphamide, doxorubicin, and vincristine, and leads to some durable remissions and cure. Unfortunately, the long-term overall survival is less than 50% with R mini CHOP. And so although this is an appropriate backbone, there's certainly a lot of room for improvement. And there's also toxicity even with R mini CHOP. So in their initial phase II trial, there was actual deaths related to the R mini CHOP, particularly in the first cycle or two, really necessitating some type of pre-phase help ease patients into the chemotherapy. One of the challenges that we face in the clinic is that when we meet an older patient, we both want to maximize our chance for cure, but also minimize the toxicity that is particularly pronounced. And there is very little data in terms of how to guide this at the bedside. I'm excited that SWOG, with the US Intergroup, is conducting a trial, S1918, which prospectively includes a frailty assessment tool that was developed by the Italian group in lymphoma, and then also includes serial comprehensive geriatric assessment so that we can get a better idea about quality of life both during and after treatment. So there is no great standard of care right now, but I would say that R mini CHOP, outside of a trial, is a very reasonable way to proceed. PAOLO STRATI: Dr. Smith, thank you for outlining so well what we can do to minimize toxicity and to better select patients for this type of treatment. And as an Italian practitioner in the United States, I am very excited that the Italian frailty tool will be used in this SWOG trial. Are there any other ways to further improve safety when we use chemo immunotherapy in older patients or patients with comorbid health conditions? In particular, there is a lot of concern about potentially infectious complications in these patients. And so I'm wondering if there's any routine antimicrobial prophylaxis that you recommend. SONALI SMITH: Yes. I think it's really important to maximize supportive care for our older patients with aggressive lymphomas getting intensive therapy. I did mention the pre-phase, and I would just like to mention that one more time because I do think there's data that providing a brief pre-phase can minimize toxicity with the first cycle. And how this pre-phase is given is highly variable. Again, the data is somewhat limited, but it typically includes steroids given for five to seven days with or without a dose of vincristine. And steroids themselves can have toxicity. And the dose of the steroids, I think, is somewhat controversial. In my personal practice, I use somewhere between 40 to 60 milligrams per day for five to seven days. And I do not typically use vincristine, although a prospective French trial recently did and showed that this significantly improved toxicity. Other complications that can occur really are related to infection. And so, of course, all patients should have growth factor support as per ASCO guidelines. But I also routinely give VZV prophylaxis with acyclovir or valacyclovir. And for the first cycle in particular, I have patients come back to clinic after the first dose one week later to ensure that the counts are stable and that they are doing well. This is really where our team of nurses and other providers who are part of the care team are so important and communication is also very important. PAOLO STRATI: So Dr. Smith, as you suggested, also, this patient actually received mini R-CHOP without any complications. And end-of-treatment PET/CT can showed a VL score of 3, so a complete metabolic remission, potentially. How do you interpret these findings? SONALI SMITH: So response criteria in clinical trials, and then of course, extrapolated to the clinic, have evolved in lymphoma. And the Deauville or the International Prognostic Scoring System that has been used typically defines a uptake relative to liver and mediastinal blood pool. And those patients who have a Deauville 1 to 2, which is less than that bar, is considered negative. And 4 to 5 is positive, with five being the emergence of new sites of adenopathy. The interpretation of a Deauville 3 can be somewhat more complicated, but this really outlines the limitations of just using the SUV or the PET scan uptake to measure response. For my patient and for this patient, the lymph nodes all substantially decreased in size. And having some type of combined interpretation of the uptake, as well as the size that has decreased, I think is going to be a very important part of how we approach patients going forward. So for this patient, I opted for close observation after the completion of therapy and felt that his Deauville 3, along with the decrease in the size of the lymph nodes, was very significant. PAOLO STRATI: I completely agree with that. Where PET scan is an extremely helpful tool, particularly for the management of aggressive B-cell lymphoma, can also become a major challenge when it comes to its interpretation for these borderline scenarios. And as you said, it's very important to add into the equation multiple parameters, including CT findings and overall patient performance status symptoms. So that's all we have for today. Thank you, Dr. Smith. This was a great conversation. We have learned and discussed a lot about diffuse large B-cell lymphoma, including novel biological agents, CAR-T cell therapy, management of elderly patients, and patients with comorbid health conditions and interpretation of PET/CT scan. I think this will be very helpful. And the conversation will continue beyond this podcast. In part 2 of this episode, airing in November, we will discuss new therapies for mantle cell lymphoma and for follicular lymphoma. Thank you so much to all the listeners tuning into this episode of the ASCO Educational Podcast. SONALI SMITH: Thank you. It's been a pleasure to speak with you today. [MUSIC PLAYING] SPEAKER: Thank you for listening to this week's episode of the ASCO e-learning weekly podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.

A 2016 study found that more than 50% of the population said they'd prefer public spaces like offices, hotels, airplanes and healthcare facilities be fragrance-free. Despite this, fragrance use is ubiquitous: it's found in everything from perfumes, beauty products, and cleaning supplies to plastics, paints, and disinfectants. The problem with these synthetic and artificial fragrances is the health effects they can have on our bodies. Chemicals used to create or prolong these “fresh” scents often have deleterious effects on our health like neurological, metabolic, respiratory, and hormonal imbalances. Today's episode continues the summer series, answering your questions about hormones. Listen in as Erin gets into the nitty gritty answering your questions about fragrance effects on hormone health, and lays out what to be aware of in products we often use on our bodies or in our home. This is a topic everyone can benefit from because most people don't even know how toxic synthetic fragrances are, nor how pervasive they are in products many of us use daily. In this episode: -Small steps we can take to get closer to non toxic living [4:38] -Starting with the basics [6:56] -Fragrance and endocrine disruptors [8:11] -“Overly sensitive” or canaries in the coalmine? [11:30] -A non exhaustive list of product types that contain artificial or synthetic fragrances [13:02] -The real problem with fragranced products [17:16] -How these fragrances can affect our health [19:28] -Why and how synthetic fragrances linger [22:17] -VOCs: what they are and common sources [23:36] -Best way to protect yourself from outdoor pollution [25:27] -Let's talk about phthalates [26:08] -Xenoestrogens and estrogen dominance [27:58] -How these chemicals impact our metabolism [29:55] -Mitochondrial dysfunction symptoms [32:11] Resources mentioned: Your Hormone Revival™ (get on the waitlist - next round starts Sept 19th!) https://www.erinholthealth.com/hormones Forrester Cabinets: https://forrestercabinets.com/ Research articles about fragrance: FRAGRANCE IN THE WORKPLACE IS THE NEW SECOND-HAND SMOKE http://www.national-toxic-encephalopathy-foundation.org/fragsmoke.pdf Scientific American's Scent of Danger: Are There Toxic Ingredients in Perfumes and Colognes https://www.scientificamerican.com/article/toxic-perfumes-and-colognes/ The Danger of Toxic Consumer Products, Fragrances https://www.huffpost.com/entry/toxic-chemicals_b_625648 Fragranced consumer products: exposures and effects from emissions https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093181/ Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls https://pubmed.ncbi.nlm.nih.gov/20308033/ Phthalates induce proliferation and invasiveness of estrogen receptor-negative breast cancer through the AhR/HDAC6/c-Myc signaling pathway https://pubmed.ncbi.nlm.nih.gov/22049059/ Exposure to Environmental Endocrine Disruptors and Child Development https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572204/ Baby Care Products: Possible Sources of Infant Phthalate Exposure https://pediatrics.aappublications.org/content/121/2/e260?sso=1&sso_redirect_count=1&nfstatus=401&nftoken=00000000-0000-0000-0000-000000000000&nfstatusdescription=ERROR%3a+No+local+token Adipose Tissue as a Site of Toxin Accumulation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101675/ The Impact of Bisphenol A and Phthalates on Allergy, Asthma, and Immune Function: a Review of Latest Findings https://link.springer.com/article/10.1007/s40572-015-0066-8 Concentrations of Urinary Phthalate Metabolites Are Associated with Increased Waist Circumference and Insulin Resistance in Adult U.S. Males https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892109/ Phthalates and Metabolism: Exposure Correlates with Obesity and Diabetes in Men https://ehp.niehs.nih.gov/doi/full/10.1289/ehp.115-a312b Fragranced consumer products: exposures and effects from emissions https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093181/ Organifi supplement powder (save 20% on your order with code FUNK) https://organifi.com/FUNK Coyote River Hemp Co CBD products (save 10% & free shipping on your order with code FUNK10) https://coyoteriverhempco.com/ Bio-Kult Boosted probiotic supplement (save 15% on your order with code FUNK15) https://www.bio-kult.com/bio-kult-boosted/p9 Follow Erin on Insta https://www.instagram.com/the.funktional.nutritionist/ Related pods: Ep 48: Exploring Female Hormones & Birth Control with Dr. Jolene Brighten https://www.erinholthealth.com/funktional-nutrition-podcast/2019/2/14/48-exploring-female-hormones-amp-birth-control-with-dr-jolene-brighten Ep 55: How to Tell if Your Blood Sugar is a Problem https://www.erinholthealth.com/funktional-nutrition-podcast/2019/4/3/episode-55? Ep 65: Everything You Ever Wanted to Know About Weight Loss erinholthealth.com/funktional-nutrition-podcast/2019/6/20/episode-65-everything-you-ever-wanted-to-know-about-weight-loss

MYC 2021

MYC 2021

MYC 2021

MYC 2021

MYC 2021

Hoy, en "Misterios y Cubatas", os traemos el audio de Twitch donde compartimos el Ranking de Mejores Momentos de MYC elaborado por parroquiers. A partir de vuestras propuestas, elaboramos una lista TOP y nos descojonamos lo que no está escrito. ¿Está tu mejor momento en esta lista? Solo lo sabrás si escuchas este programa. Así que ya sabes, elige tu bebida y aperitivos, que vamos a pasar una hora de chinchorreo. ¿Te apetece? ¡Pues dale fufa al PLAY! ▶️ No te olvides de seguirnos en redes sociales y si te echas unas risas, ¡comparte y comenta el podcast! - Instagram: @misteriosycubatas - Twitter: @misterioycubata - Twitch: misteriosycubatas - Ko-Fi: https://ko-fi.com/misteriosycubatas Dirige y presenta: Sére Skuld

MYC 21- The glory that excelleth

MYC 21- The glory that excelleth

MYC 21- The glory that excelleth

MYC 21- The glory that excelleth

MYC 21- The glory that excelleth

On this episode Tyler D and Jarrell review new albums from AFI, Migos & Garbage. In Entertainment (Music) News, Jarrell sadly announces the future closing of legendary New Jersey Record Store Vintage Vinyl.Website: Puppetperspectives.comFacebook: facebook.com/puppetreviews15Twitter: @puppetreviews15Instagram: @puppetreviews15

In this episode we chat with Chattanooga FC's David Smotherman, Director of Merchandise and Owen Seaton, Chief Marketing Officer.   We talk about their soccer history, MyC***o, David's mad soccer skills, and much much more.    You can find David on twitter @CFCMerchBooth and @cfcmerchguy    Find Owen on twitter at @CFC_CMO and @SeatonOB    Find us on twitter at @section109pod    Find us on instagram at @section109podcast

Dr. Alberto Martin discusses A 1985 paper demonstrating that cancer could be caused by a non-mutated version of Myc

We discuss WWE No Mercy main event, Quarter & semi finals of MYC, and who should leave WWE.