Podcasts about Oncogene

In this episode of THE MENTORS RADIO, host Tom Loarie talks with Justin Stebbing, M.D., a London-based, world-renown scientist, cancer researcher, medical journal editor and author. Dr. Stebbing talks about the excitement and rewards of a STEM career, the life of a scientist, and about his own journey to becoming a world-renown clinician and scientist. He also about the tremendous wonder of discovering improved therapies for cancer and for treating covid. Professor Justin Stebbing, M.D., is also a professor of biomedical sciences at ARU, Cambridge, and a visiting professor at Imperial College where he has an active and widely known translational laboratory. He is the author of more than 700 peer-reviewed papers published in The Lancet, The New England Journal of Medicine and elsewhere. Dr. Stebbing is the co-chief editor of Oncogene and author of the book, Witness to Covid. Find Show Notes below. Listen to this episode below and on ANY podcast platform (from Apple to Spotify, Google, Stitcher, Spotify, TuneIn, etc) by typing in “THE MENTORS RADIO” … even easier, Subscribe HERE to listen on any podcast platform!!! SHOW NOTES: JUSTIN STEBBING, M.D.: BIO: https://www.imperial.ac.uk/people/j.stebbing AND https://justinstebbing.me/ BOOK: Witness to Covid: The diary of a global pandemic, by Professor Justin Stebbing ARTICLES: PROFESSOR JUSTIN STEBBING: The revolution that makes me believe we really CAN beat cancer in my lifetime

In today's episode, we had the pleasure of speaking with Alec Watson, MD, a thoracic oncology fellow in the School of Medicine in the Division of Medical Oncology at the University of Colorado Anschutz Medical Campus in Aurora. In our exclusive interview, Dr Watson discussed the rationale for and key findings from a retrospective analysis examining the ways that oncogene overlap could identify clinically relevant thresholds for MET, KRAS, and HER2 gene copy number gain in non–small cell lung cancer; next steps for this research; and the future implications of these findings.

Dr. Keith Ellis is a Scientist and Associate Professor of Medicinal Chemistry that is dedicating his time, energy, and talents to helping people recover from Long Covid. Dr. Ellis is using his knowledge, expertise, and experience in medicinal chemistry, pharmacology, and natural products to research the biological mechanisms that cause Long Covid and the potential therapeutic mechanisms that can help people recover. Combining this scientific work with his interest in entrepreneurship, Dr. Ellis has designed and brought to market a custom-formulated natural product supplement to help people recover from Long Covid. In 2023, Dr. Ellis founded Science-Driven Supplements and launched its first product: CircuGuard - a natural, herbal supplement to help people recover from Long Covid microclots. Dr. Ellis and Science-Driven Supplements are committed to creating custom-formulated solutions for people with Long Covid that are safe, inexpensive, accessible for everyone without a doctor's prescription, and available RIGHT NOW. Several more products targeting other underlying biological mechanisms of Long Covid are in the design phase and will be launched in the coming year. In parallel with his Long Covid research and work as Founder of Science-Driven Supplements, Dr. Ellis serves as an Associate Professor of Medicinal Chemistry conducting academic research in early lead discovery in the oncology field and teaching organic and medicinal chemistry to graduate students, professional students, and undergraduates. Dr. Ellis has published academic scholarly work in world-class scientific journals including: the Journal of Natural Products, ACS Medicinal Chemistry Letters, ACS Chemical Biology, Molecular Pharmacology, Oncotarget, Oncogene, Bioorganic & Medicinal Chemistry, and Cancer Biology & Therapy. Career Highlights: Founder - Science-Driven Supplements, LLC - 2023 Faculty PositionsVirginia Commonwealth University, Richmond, VAAssociate Professor of Medicinal Chemistry (with Tenure) - 2018-presentAssistant Professor of Medicinal Chemistry - 2008-2018 Education and Professional TrainingBA Cum Laude (Chemistry) - 1999 - Cornell University, Ithaca, NYPhD (Chemistry) - 2004 - University of Virginia, Charlottesville, VAPost-Doctoral Researcher - 2005-2006 - Department of Medicinal Chemistry, University of Kansas, Lawrence, KSResearch Associate - 2007-2008 - Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN Long Covid Research, Social Media Links, and LinkedIn Profile can be found at www.keithcellisphd.com.

References FEMS Microbiol Rev.1998. Oct;22(4):255-75 Discoveries(Craiova). 2017 Jul-Sep; 5(3): e77. J Cell Mol Med. 2015 Jul; 19(7): 1427–1440. Oncogene. 2017 Mar 23; 36(12): 1607–1618. Bach, JS. 1742. Kunst der Fuge , BWV 1080; Marta Czech https://youtu.be/p1Sq1HOYglU?si=2GMF7kf3dLW4rr2O Lennon and MCartney.1968. "Martha my Dear" https://youtu.be/RXawa90YU2s?si=dUPDtTdm4UqrgWit --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

References Front. Oncol. 2017. 26 November.V.7. Oncogene. 2017 Mar 23; 36(12): 1607–1618. Schubert, F. 1819 Piano Quintet in A major, D. 667/ "Trout" https://youtu.be/syod5rkFdNY?si=5F3rexiou7dTifYg Hunter, R., Garcia , J. 1970 "Ripple" https://youtu.be/xofhZx9eWUQ?si=tpOAMzyW5qUy01P_ --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

References Cancers (Basel). 2019 May; 11(5): 678. Oncogene.2017 Mar 23; 36(12): 1607–1618 Dr Guerra's annotated lecture notes from graduate biochemistry course(s) --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message

References Front. Cell Dev. Biol., 26 March2021 Sec. Molecular and Cellular Oncology Volume 9 Cancer Drug Resist 2020;3:762-74. Oncogene.2017 Mar 23; 36(12): 1607–1618 Front Immunol. 2020; 11: 1782. --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message

A new editorial paper was published in Oncotarget's Volume 14 on February 11, 2023, entitled, “Unveiling the non-canonical functions of EZH2 in prostate cancer.” Prostate cancer (PCa) is ranked as the second leading cause of cancer-related death among American men excluding skin cancer. In this new editorial, researchers Yang Yi, Yanqiang Li, Kaifu Chen, and Qi Cao from Northwestern University's Feinberg School of Medicine discuss a well-known oncogenic driver in PCa: enhancer of zeste homolog 2 (EZH2)—canonically known for the functions as the catalytic subunit of Polycomb Repressive Complex 2 (PRC2) that deposes histone H3 lysine 27 mono, di-, and tri-methylation (H3K27me1-3) and represses transcription. “Although the oncogenic role of EZH2 mainly relies on its enzymatic activity and the PRC2, accumulating evidence suggests that targeting the lysine methyltransferase activity of EZH2 alone is ineffective in treating EZH2-dependent malignancies including PCa [4, 5].” Hence, deeply investigating the multifaceted tumorigenic functions of EZH2 will shed new light on understanding the etiology of PCa. It is noteworthy that two recent studies published in Nature Cell Biology and Oncogene by Yi et al. described previously unrecognized roles of EZH2 in regulation of translation and coactivation of transcription, respectively. In both cases, EZH2 exerts oncogenic functions independently of PRC2 and H3K27me3 to promote tumorigenesis and aggressiveness in PCa. “In summary, both articles by Yi et al. emphasized the significance of non-canonical functions of EZH2 during PCa development, which may provide novel insights into the advancement of EZH2-targeting strategies to treat PCa patients. In fact, a new wave has been ushed for the discovery of EZH2 inhibitors to eliminate both the catalytic and non-catalytic activities of EZH2 [12–14]. Will these newly developed EZH2 degraders be successfully applied in PCa therapy? Will additional noncanonical functions of EZH2 be characterized in the PCa model? Let's eagerly wait and see.” Full editorial: DOI: https://doi.org/10.18632/oncotarget.28357 Correspondence to: Qi Cao - qi.cao@northwestern.edu Keywords: EZH2, prostate cancer, FBL, CDCA8, E2F1 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28357 Keywords - EZH2, prostate cancer, FBL, CDCA8, E2F1 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 and 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/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

In this episode, host Tom Loarie talks with London-based, world-renown scientist, cancer researcher, medical journal editor and author, Justin Stebbing, M.D. They discuss the excitement and rewards of a STEM career, the life of a scientist, Dr. Stebbing's journey to becoming a world renown clinician and scientist and the wonders of discovering improved therapies for cancer and for treating covid. Professor Justin Stebbing, M.D., is also a professor of biomedical sciences at ARU, Cambridg and a visiting professor at Imperial College where he has an active and widely known translational laboratory. He is the author of more than 700 peer-reviewed papers published in The Lancet, The New England Journal of Medicine and elsewhere. He is the co-chief editor of Oncogene and author of the book, Witness to Covid. Find Show Notes below. Listen to this episode below and on ANY podcast platform (from Apple to Google to Stitcher, Spotify, TuneIn, etc) by typing in “THE Mentors RADIO” … even easier, Subscribe HERE to listen on any podcast platform!!! SHOW NOTES: JUSTIN STEBBING, M.D.: BIO: https://www.imperial.ac.uk/people/j.stebbing AND https://justinstebbing.me/ BOOK: Witness to Covid: The diary of a global pandemic, by Professor Justin Stebbing ARTICLES: PROFESSOR JUSTIN STEBBING: The revolution that makes me believe we really CAN beat cancer in my lifetime

The 2019 Cell Reports paper, “Chromatin Remodeling in Response to BRCA2-Crisis” by J Gruber and M Snyder et al. is available online here.Dr. Michael Snyder's Stanford laboratory home page is here.A 1998 Oncogene paper, “The BRCA2 is a histone acetyltransferase” by S Habibur and E S P Reddy et al. is located online here. A 2014 Cancer Discovery paper, “R-loop Processing by BRCA2 is Required for Genomic Stability” is located here. And more about TIP60 can be found in this recent 2022 Oncogenesis reference, “The TIP60-ATM axis regulates replication fork stability in BRCA-deficient cells” located online here. If you would like to contact Dale, Cindy or Sarantis feel free to email us at info@olink.com and if you would like to learn more about our backgrounds, Cindy's LinkedIn is here, Sarantis' is here, and Dale's is here.In case you were wondering, Proteomics in Proximity refers to the principle underlying Olink Proteomics assay technology called the Proximity Extension Assay (PEA), and more information about the assay and how it works can be found here.Would you like to subscribe to the podcast on your favorite player or app? You can do so here: Apple Podcasts: https://apple.co/3T0YbSm Spotify Podcasts: https://open.spotify.com/show/2sZ2wxOqI4b4vSngkajLs8?si=d957d55c8db046f7 Google Podcasts: https://podcasts.google.com/feed/aHR0cHM6Ly9mZWVkcy50cmFuc2lzdG9yLmZtL3Byb3Rlb21pY3MtaW4tcHJveGltaXR5 Amazon Music: https://music.amazon.com/podcasts/d97ace94-f02b-4b37-9532-799548ef2840 Podcast Addict: https://podcastaddict.com/podcast/4098296 Deezer: https://www.deezer.com/show/5178787 Player FM: https://player.fm/series/series-3396598

In this episode, experts explore new data related to EGFR TKI resistance, specifically resistance to osimertinib. Listen to our experts evaluating the real-world data on most common resistance mechanisms to osimertinib and emerging strategies to overcome resistance. 

In this episode, our experts discuss current and new strategies for targeting KRAS G12C mutation. Hear about emerging strategies to enhance activity of current treatment options in this molecular subtype. 

In this episode two experts discuss new data presented at WCLC on targeting MET ex14 skipping mutations. Listen to the latest evidence on managing this rare molecular subtype and how these data may impact clinical practice. 

Deme Karikios, Medical Oncologist and Director of Clinical trials at Nepean Cancer Care Centre in Sydney is joined by Wanda Cui, Medical Oncologist from the Peter MacCallum Cancer Centre in Melbourne and Chris Karapetis,  Head of the Department of Medical Oncology and Director of Clinical Research at the Flinders Medical Centre in Adelaide.

In this episode of the Epigenetics Podcast, we caught up with Erna Magnúsdóttir from the University of Iceland to talk about her work on the role of Blimp-1 in immune-cell differentiation. The Magnúsdóttir Lab is interested in how the mammalian genome is interpreted in a context dependent manner, leading to different cellular states, by using mouse primordial germ cells as well as mouse and human B-cells as model systems. More specifically, the team is interested in the Transcription Factor Blimp-1 and its effect on immune cell differentiation. Next to its function in immune cells, Blimp-1 also plays a role in Waldenström's macroglobulinemia. The lab hopes to reveal the intricacies in disease progression and alteration in cellular states to increasingly aggressive tumor behavior.   References Magnúsdóttir, E., Dietmann, S., Murakami, K. et al. A tripartite transcription factor network regulates primordial germ cell specification in mice. Nat Cell Biol 15, 905–915 (2013). https://doi.org/10.1038/ncb2798 Anderson, K.J., Ósvaldsdóttir, Á.B., Atzinger, B. et al. The BLIMP1—EZH2 nexus in a non-Hodgkin lymphoma. Oncogene 39, 5138–5151 (2020). https://doi.org/10.1038/s41388-020-1347-8   Related Episodes Pioneer Transcription Factors and Their Influence on Chromatin Structure (Ken Zaret) DNA Methylation and Mammalian Development (Déborah Bourc'his) The Role of SMCHD1 in Development and Disease (Marnie Blewitt)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

Featuring perspectives from Drs Marc Ladanyi, Andrew McKenzie and Helena Yu, including the following topics: Introduction: Role of Genomic Profiling in Non-Small Cell Lung Cancer (NSCLC) (0:00) Case: A woman in her mid-40s with newly diagnosed Stage IIB adenocarcinoma of the lung and an EGFR L858R mutation — Helena Yu, MD (13:33) Case: A man in his late 70s with metastatic NSCLC and osimertinib resistance due to acquired RET fusion — Marc Ladanyi, MD (23:08) Case: A woman in her mid-60s with newly diagnosed adenocarcinoma of the lung and an EGFR exon 20 mutation — Dr Yu (27:28) Case: A man in his late 70s with Stage IV adenocarcinoma of the lung and a RET fusion — Andrew J McKenzie, PhD (36:49) Case: A man in his late 60s with metastatic mucinous adenocarcinoma of the lung and a HER2 mutation — Spencer Bachow, MD (46:01) Case: A woman in her mid-30s with newly diagnosed metastatic NSCLC and an ALK mutation — Nikesh Jasani, MD (51:57) Case: A man in his late 70s with NSCLC and a TRK fusion — Dr McKenzie (53:24) Case: A woman in her mid-60s with discordant BRAF mutation testing results — Syed Zafar, MD (55:41) CME information and select publications

Featuring perspectives from Drs Marc Ladanyi, Andrew McKenzie and Joel Neal, including the following topics: Introduction (0:00) Role of Genomic Profiling; New Developments in Non-Small Cell Lung Cancer (NSCLC) with an EGFR Mutation (0:49) Case: A woman in her early 60s with NSCLC and an EGFR exon 19 deletion — Andrew J McKenzie, PhD (30:40) Case: A man in his early 50s with metastatic lung adenocarcinoma and an EGFR exon 20 mutation — Atif Hussein, MD, MMM (35:04) Case: A man in his early 50s with RET positive NSCLC — Joel W Neal, MD, PhD (48:48) Case: A woman in her mid-60s with metastatic NSCLC and a HER2 exon 20 insertion — Dr Neal  CME information and select publications

Este episodio se grabó el 16 de julio de 2021, en el estudio de grabación de la Facultad de Ciencias de la Comunicación (Universidad de Málaga). Como siempre, os presentamos una tertulia con la actualidad de la semana en investigación biomédica. Tras la presentación, comenzamos (min. 04:00) hablando de una noticia que ha causado bastante revuelo mediático en los círculos científicos: el anuncio, por parte de dos reputadas investigadoras, la microbióloga Jill Banfield y la premio Nobel Jennifer Doudna (ambas de la Universidad de California, Berkeley), de unas misteriosas secuencias de ADN previamente desconocidas, únicas y "absolutamente fascinantes” a las que han bautizado con el rimbombante nombre de BORGs (la referencia es: Al-Shayeb et al.. Borgs are giant extrachromosomal elements with the potential to augment methane oxidation. bioRxiv 2021.07.10.451761. https://doi.org/10.1101/2021.07.10.451761). De todo este “hype” charlamos entre nosotros y con uno de nuestros mayores expertos en metagenomas (min 21:45), el profesor Francisco Rodríguez-Valera (Universidad Miguel Hernández, Elche). A continuación (min 38:30), los reporteros más dicharacheros, Belén e Íker, nos traen la sección de (bio)noticias: el impacto que ha tenido la campaña mundial de vacunación contra la COVID19 en las otras, ya establecidas, campañas anuales; la relación entre consumo de alcohol y cáncer y la publicación en Nature del código fuente de AlphaFold, un algoritmo basado en redes neuronales de predicción de estructuras tridimensionales de proteínas, creado por DeepMind (el programa de inteligencia artificial de Google) y que aspira a ser la gran revolución en Biología Estructural de este siglo (la referencia es: Jumper et al. (2021). Highly accurate protein structure prediction with AlphaFold. Nature 1–11. https://doi.org/10.1038/s41586-021-03819-2). Desde luego, los primeros resultados son muy prometedores y, aunque aún requiere más entrenaniento, las espectativas son elevadas. Nuestro experto bioinformático, Francis, nos da su opinión sobre este asunto y aprovecha para comentarnos (min. 58:00) otro artículo, publicado el mismo día, pero en Science, en el que se anuncia otro algoritmo surgido, como AlphaFold, de la iniciativa CASP (Critical Assessment of Techniques for Protein Structure Prediction) y que promete ser un digno competidor: RoseTTAFold (la referencia es: Baek et al. (2021). Accurate prediction of protein structures and interactions using a three-track neural network. Science eabj8754. DOI: 10.1126/science.abj8754). Por último (min. 69:00), Pepe comenta un trabajo del grupo de Nuria Bigas y Lluís Espinosa (Hospital del Mar, Barcelona), recién publicado en Oncogene, en el que proponen una nueva terapia contra el melanoma basada en la combinación de un inhibidor específico del oncogén BRAF y la quimioterapia clásica. El propio Dr. Espinosa comenta con nosotros, via telefónica, los principales aspectos de este descubrimiento y sus implicaciones terapéuticas (la referencia es: Alonso-Marañón et al. (2021). Combination of chemotherapy with BRAF inhibitors results in effective eradication of malignant melanoma by preventing ATM-dependent DNA repair. Oncogene 1–7. https://doi.org/10.1038/s41388-021-01879-2). Esperamos que os guste BS16. Gracias por seguir ahí. (Audios de la misión Apolo 11, NASA: https://go.nasa.gov/3hZv5TH. Audios del Trinity nuclear test: https://bit.ly/3BxDk10)

Prof Perol summarizes the key information from Medscape’s live symposium on EGFR exon 20 insertions and ALK-positive NSCLC. Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/950660?src=mkm_podcast_addon_950660

Gene editing, amazing technology, and personalized medicine?! From advancements in treatment to providing insight on improving rates of survival, cancer PhD student and friend of the show Erin Marshall (University of British Columbia) has us covered. Together we explain a big misconception of cancer, share some of the mind blowing research developments in the world of oncology, and how these advancements have made “cancer startups” all the rage.Join us as we dig into the health headlines you already know and tell you more about the ones you don't. Twitter: @SickHealthShowInstagram: @SickHealthShowRitual Music Promotion: https://www.ritualmusic.com/r/SickHealthShow CreditsThanks to Erin Marshall, the expert guest on the episodeLogo design: Brad HartMusical theme: Double Whistle TripHop by Down 7 thanks to RitualMusic.comEditor: Mack Britton LinksThe top 10 causes of deathStatistics Canada - Leading causes of deathBC Cancer Foundationhttps://cc-arcc.ca/wp-content/uploads/2015/01/Current-gotay.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209562/https://www.globenewswire.com/news-release/2020/12/11/2143509/0/en/Metastatic-Cancer-Treatment-Market-Size-To-Be-Worth-USD-111-16-Billion-by-2027-Emergen-Research.htmlhttps://www.cancer.ca/en/about-us/our-research/?region=on#:~:text=In%202019%E2%80%932020%2C%20the%20Canadian,in%20the%20future%20of%20cancer. https://www.nap.edu/resource/25665/Heritable%20Human%20Genome%20Editing%20Report%20Summary%20-%20FINAL%2020200903.pdfhttps://www.sciencemag.org/news/2018/11/crispr-bombshell-chinese-researcher-claims-have-created-gene-edited-twinshttps://www.theatlantic.com/science/archive/2018/12/15-worrying-things-about-crispr-babies-scandal/577234/https://www.nature.com/articles/d41586-019-00673-1https://www.sciencemag.org/news/2019/08/did-crispr-help-or-harm-first-ever-gene-edited-babieshttps://www.nap.edu/resource/25665/Heritable%20Human%20Genome%20Editing%20Report%20Summary%20-%20FINAL%2020200903.pdf

Reference List: 1. Aune D, Chan DS, Vieira AR, et al. Dietary compared with blood concentrations of carotenoids and breast cancer risk: a systematic review and meta-analysis of prospective studies. Am J Clin Nutr 2012, 96:356-373. doi: 10.3945/ajcn.112.034165 2. Thomson CA, Rock CL, Thompson PA, et al. Vegetable intake is associated with reduced breast cancer recurrence in tamoxifen users: a secondary analysis from the Women's Healthy Eating and Living Study. Breast Cancer Research and Treatment 2011, 125:519-527. doi: 10.1007/s10549-010-1014-9 3. Lee SA, Fowke JH, Lu W, et al. Cruciferous vegetables, the GSTP1 Ile105Val genetic polymorphism, and breast cancer risk. Am J Clin Nutr 2008, 87:753-760. 4. Seow A, Yuan JM, Sun CL, et al. Dietary isothiocyanates, glutathione S-transferase polymorphisms and colorectal cancer risk in the Singapore Chinese Health Study. Carcinogenesis 2002, 23:2055-2061. doi: 10.1093/carcin/23.12.2055 5. Zhang X, Shu XO, Xiang YB, et al. Cruciferous vegetable consumption is associated with a reduced risk of total and cardiovascular disease mortality. Am J Clin Nutr 2011, 94:240-246. doi: 10.3945/ajcn.110.009340 6. Darmadi-Blackberry I, Wahlqvist ML, Kouris-Blazos A, et al. Legumes: the most important dietary predictor of survival in older people of different ethnicities. Asia Pac J Clin Nutr 2004, 13:217-220. doi: 7. Piccolo E, Vignati S, Maffucci T, et al. Inositol pentakisphosphate promotes apoptosis through the PI 3-K/Akt pathway. Oncogene 2004, 23:1754-1765. doi: 10.1038/sj.onc.1207296 8. Galeone C, Pelucchi C, Levi F, et al. Onion and garlic use and human cancer. Am J Clin Nutr 2006, 84:1027-1032. doi: 10.1093/ajcn/84.5.1027 9. Thompson LU, Chen JM, Li T, et al. Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer. Clin Cancer Res 2005, 11:3828-3835. doi: 10.1158/1078-0432.CCR-04-2326 10. McCann SE, Thompson LU, Nie J, et al. Dietary lignan intakes in relation to survival among women with breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study. Breast Cancer Res Treat 2010, 122:229-235. doi: 10.1007/s10549-009-0681-x 11. Anand P, Sundaram C, Jhurani S, et al. Curcumin and cancer: an "old-age" disease with an "age-old" solution. Cancer Lett 2008, 267:133-164. doi: 10.1016/j.canlet.2008.03.025 12. Giovannucci E, Rimm EB, Liu Y, et al. A prospective study of tomato products, lycopene, and prostate cancer risk. J Natl Cancer Inst 2002, 94:391-398. doi: 10.1093/jnci/94.5.391 13. Grainger EM, Schwartz SJ, Wang S, et al. A combination of tomato and soy products for men with recurring prostate cancer and rising prostate specific antigen. Nutr Cancer 2008, 60:145-154. doi: 10.1080/01635580701621338

Join us for a conversation with internationally recognized Medical Oncologists and researchers, Professor Ben Solomon & Associate Professor Tom John as they discuss the increased survival benefits for patients with oncogene driven lung cancer and how novel treatments are contributing.Oncogenes discussed include EGFR & osimertinib; ALK & brigatinib, alectinib, lorlatinib; ROS1 & crizotinib, entrectinib; KRAS & sotorasib; G12C; Exon20 insertions & poziotinib, amivantamab, RET & selpercatinib, pralcetinib. Also discussed – the importance of the move beyond single gene testing to panels and NGS is important to maximise turn-around times and the efficient utilization of clinical samples.

Episode 347 is an updated guide to somatropic hormone and GOD did I go crazy on this one! I honestly want to know more about growth hormone than anyone alive and thus, begins this string of GH based guides! I DID finally discuss the MoA for how GH causes localized fat loss which really had me excited since no one in our industry has EVER talked about this so that definitely was an interesting avenue to go down! Below I am going to reference a lot of the literature for this hormone that I was read through over the past few years on this topic so please DO NOT TAKE MY WORD FOR THIS - READ THESE YOURSELF! Keep in mind this is a brief snippet of every bit of literature on the topic however. REFERENCES   Daughaday WH, Rotwein P. Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocr Rev. 1989;10:68–91. [PubMed] [Google Scholar] Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 1995;16:3–34. [PubMed] [Google Scholar] Le Roith D, Bondy C, Yakar S, Liu JL, Butler A. The somatomedin hypothesis: 2001. Endocr Rev. 2001;22:53–74. [PubMed] [Google Scholar] Melmed S. Endocrinology. 5th edn. Philadelphia: Elsevier Saunders; 2006. pp. 411–428. [Google Scholar] Fain, J. N., García‐Sáinz, JA. (1983) Adrenergic regulation of adipocytes metabolism. J Lipid Res 24: 945– 966. CAS PubMed Web of Science®Google Scholar  Gilman, AG. (1987) G protein: transducer of receptor‐generated signals. Annu Rev Biochem 56: 615– 649. Crossref CAS PubMed Web of Science®Google Scholar  Jimenez, M., Lèger, B., Canola, K., et al (2002) Beta(1)/beta(2)/beta(3)‐adrenoceptor knockout mice are obese and cold‐sensitive but have normal lipolytic responses to fasting. FEBS Lett 530: 37– 40. Wiley Online Library CAS PubMed Web of Science®Google Scholar  Birnbaumer, L., Abramowitz, J., Brown, AM. (1990) Receptor‐effector coupling by G proteins. Biochim Biophys Acta 1031: 163– 224. Crossref CAS PubMed Web of Science®Google Scholar  Spiegel, A. M., Shenker, A., Weinstein, LS. (1992) Receptor‐effector coupling by G‐protein: implications for normal and abnormal signal transduction. Endocr Rev 13: 536– 565. Crossref CAS PubMed Web of Science®Google Scholar  Beebe, S. J., Holloway, R., Rannels, R. S., Corbin, JD. (1984) Two classes of cAMP analogs which are selective for the two different cAMP‐binding sites of type II protein kinase demonstrate synergism when added together to intact adipocytes. J Biol Chem 269: 3539– 3547. PubMed Google Scholar Frank RN. Diabetic retinopathy. N Engl J Med. 2004;350:48–58. [PubMed] [Google Scholar] Tatar M, Bartke A, Antebi A. The endocrine regulation of aging by insulin-like signals. Science. 2003;299:1346–1351. [PubMed] [Google Scholar] Ibrahim YH, Yee D. Insulin-like growth factor-I and cancer risk. Growth Horm IGF Res. 2004;14:261–269. [PubMed] [Google Scholar] Laban C, Bustin SA, Jenkins PJ. The GH-IGF-I axis and breast cancer. Trends Endocrinol Metab. 2003;14:28–34. [PubMed] [Google Scholar] Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer. 2008;8:915–928. [PubMed] [Google Scholar] Mayo KE. A little lesson in growth regulation. Nat Genet. 1996;12:8–9. [PubMed] [Google Scholar] Rosenfeld RG, Rosenbloom AL, Guevara-Aguirre J. Growth hormone (GH) insensitivity due to primary GH receptor deficiency. Endocr Rev. 1994;15:369–390. [PubMed] [Google Scholar] Goddard AD, Covello R, Luoh SM, Clackson T, Attie KM, Gesundheit N, Rundle AC, Wells JA, Carlsson LM. Mutations of the growth hormone receptor in children with idiopathic short stature. The Growth Hormone Insensitivity Study Group. N Engl J Med. 1995;333:1093–1098. [PubMed] [Google Scholar] Abuzzahab MJ, Schneider A, Goddard A, Grigorescu F, Lautier C, Keller E, Kiess W, Klammt J, Kratzsch J, Osgood D, Pfaffle R, Raile K, Seidel B, Smith RJ, Chernausek SD. IGF-I receptor mutations resulting in intrauterine and postnatal growth retardation. N Engl J Med. 2003;349:2211–2222. [PubMed] [Google Scholar] Woods KA, Camacho-Hubner C, Savage MO, Clark AJ. Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. N Engl J Med. 1996;335:1363–1367. [PubMed] [Google Scholar] Lupu F, Terwilliger JD, Lee K, Segre GV, Efstratiadis A. Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth. Dev Biol. 2001;229:141–162. [PubMed] [Google Scholar] Powell-Braxton L, Hollingshead P, Warburton C, Dowd M, Pitts-Meek S, Dalton D, Gillett N, Stewart TA. IGF-I is required for normal embryonic growth in mice. Genes Dev. 1993;7:2609–2617. [PubMed] [Google Scholar] Sotiropoulos A, Ohanna M, Kedzia C, Menon RK, Kopchick JJ, Kelly PA, Pende M. Growth hormone promotes skeletal muscle cell fusion independent of insulin-like growth factor 1 up-regulation. Proc Natl Acad Sci U S A. 2006;103:7315–7320. [PMC free article] [PubMed] [Google Scholar] Fernandez AM, Dupont J, Farrar RP, Lee S, Stannard B, Le Roith D. Muscle-specific inactivation of the IGF-I receptor induces compensatory hyperplasia in skeletal muscle. J Clin Invest. 2002;109:347–355. [PMC free article] [PubMed] [Google Scholar] Coleman ME, DeMayo F, Yin KC, Lee HM, Geske R, Montgomery C, Schwartz RJ. Myogenic vector expression of insulin-like growth factor I stimulates muscle cell differentiation and myofiber hypertrophy in transgenic mice. J Biol Chem. 1995;270:12109–12116. [PubMed] [Google Scholar] Barton-Davis ER, Shoturma DI, Musaro A, Rosenthal N, Sweeney HL. Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function. Proc Natl Acad Sci U S A. 1998;95:15603–15607. [PMC free article] [PubMed] [Google Scholar] Bodine SC, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R, Zlotchenko E, Scrimgeour A, Lawrence JC, Glass DJ, Yancopoulos GD. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol. 2001;3:1014–1019. [PubMed] [Google Scholar] Musaro A, McCullagh K, Paul A, Houghton L, Dobrowolny G, Molinaro M, Barton ER, Sweeney HL, Rosenthal N. Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle. Nat Genet. 2001;27:195–200. [PubMed] [Google Scholar] Barton ER, Morris L, Musaro A, Rosenthal N, Sweeney HL. Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice. J Cell Biol. 2002;157:137– 148. [PMC free article] [PubMed] [Google Scholar] Caroni P, Schneider C. Signaling by insulin-like growth factors in paralyzed skeletal muscle: rapid induction of IGF1 expression in muscle fibers and prevention of interstitial cell proliferation by IGF-BP5 and IGF-BP4. J Neurosci. 1994;14:3378–3388. [PMC free article] [PubMed] [Google Scholar] Edwall D, Schalling M, Jennische E, Norstedt G. Induction of insulin-like growth factor I messenger ribonucleic acid during regeneration of rat skeletal muscle. Endocrinology. 1989;124:820–825. [PubMed] [Google Scholar] DeVol DL, Rotwein P, Sadow JL, Novakofski J, Bechtel PJ. Activation of insulin-like growth factor gene expression during work-induced skeletal muscle growth. Am J Physiol. 1990;259:E89–E95. [PubMed] [Google Scholar] Carson JA, Nettleton D, Reecy JM. Differential gene expression in the rat soleus muscle during early work overload-induced hypertrophy. FASEB J. 2002;16:207–209. [PubMed] [Google Scholar] Waters MJ, Hoang HN, Fairlie DP, Pelekanos RA, Brown RJ. New insights into growth hormone action. J Mol Endocrinol. 2006;36:1–7. [PubMed] [Google Scholar] Herrington J, Carter-Su C. Signaling pathways activated by the growth hormone receptor. Trends Endocrinol Metab. 2001;12:252–257. [PubMed] [Google Scholar] Lanning NJ, Carter-Su C. Recent advances in growth hormone signaling. Rev Endocr Metab Disord. 2006;7:225–235. [PubMed] [Google Scholar] Rotwein P, Thomas MJ, Harris DM, Gronowski AM, LeStunff C. Nuclear actions of growth hormone: an in vivo perspective. J Anim Sci. 1997;75:11–19. [Google Scholar] Herrington J, Smit LS, Schwartz J, Carter-Su C. The role of STAT proteins in growth hormone signaling. Oncogene. 2000;19:2585–2597. [PubMed] [Google Scholar] Levy DE, Darnell JEJ. Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol. 2002;3:651–662. [PubMed] [Google Scholar] Gronowski AM, Rotwein P. Rapid changes in nuclear protein tyrosine phosphorylation after growth hormone treatment in vivo. Identification of phosphorylated mitogen-activated protein kinase and STAT91. J Biol Chem. 1994;269:7874–7878. [PubMed] [Google Scholar] Gronowski AM, Zhong Z, Wen Z, Thomas MJ, Darnell JEJ, Rotwein P. In vivo growth hormone treatment rapidly stimulates the tyrosine phosphorylation and activation of Stat3. Mol Endocrinol. 1995;9:171–177. [PubMed] [Google Scholar] Ram PA, Park SH, Choi HK, Waxman DJ. Growth hormone activation of Stat 1, Stat 3, and Stat 5 in rat liver. Differential kinetics of hormone desensitization and growth hormone stimulation of both tyrosine phosphorylation and serine/threonine phosphorylation. J Biol Chem. 1996;271:5929–5940. [PubMed] [Google Scholar] Campbell GS, Meyer DJ, Raz R, Levy DE, Schwartz J, Carter-Su C. Activation of acute phase response factor (APRF)/Stat3 transcription factor by growth hormone. J Biol Chem. 1995;270:3974–3979. [PubMed] [Google Scholar] Smit LS, Vanderkuur JA, Stimage A, Han Y, Luo G, Yu-Lee LY, Schwartz J, Carter-Su C. Growth hormone-induced tyrosyl phosphorylation and deoxyribonucleic acid binding activity of Stat5A and Stat5B. Endocrinology. 1997;138:3426–3434. [PubMed] [Google Scholar] Smit LS, Meyer DJ, Billestrup N, Norstedt G, Schwartz J, Carter-Su C. The role of the growth hormone (GH) receptor and JAK1 and JAK2 kinases in the activation of Stats 1, 3, and 5 by GH. Mol Endocrinol. 1996;10:519–533. [PubMed] [Google Scholar] Gebert CA, Park SH, Waxman DJ. Regulation of signal transducer and activator of transcription (STAT) 5b activation by the temporal pattern of growth hormone stimulation. Mol Endocrinol. 1997;11:400–414. [PubMed] [Google Scholar] Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D, Brown M, Bodner S, Grosveld G, Ihle JN. Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell. 1998;93:841–850. [PubMed] [Google Scholar] Udy GB, Towers RP, Snell RG, Wilkins RJ, Park SH, Ram PA, Waxman DJ, Davey HW. Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. Proc Natl Acad Sci U S A. 1997;94:7239–7244. [PMC free article] [PubMed] [Google Scholar] Kofoed EM, Hwa V, Little B, Woods KA, Buckway CK, Tsubaki J, Pratt KL, Bezrodnik L, Jasper H, Tepper A, Heinrich JJ, Rosenfeld RG. Growth hormone insensitivity associated with a STAT5b mutation. N Engl J Med. 2003;349:1139–1147. [PubMed] [Google Scholar] Hwa V, Little B, Adiyaman P, Kofoed EM, Pratt KL, Ocal G, Berberoglu M, Rosenfeld RG. Severe growth hormone insensitivity resulting from total absence of signal transducer and activator of transcription 5b. J Clin Endocrinol Metab. 2005;90:4260–4266. [PubMed] [Google Scholar] Rosenfeld RG, Belgorosky A, Camacho-Hubner C, Savage MO, Wit JM, Hwa V. Defects in growth hormone receptor signaling. Trends Endocrinol Metab. 2007;18:134–141. [PubMed] [Google Scholar] Thompson BJ, Shang CA, Waters MJ. Identification of genes induced by growth hormone in rat liver using cDNA arrays. Endocrinology. 2000;141:4321–4324. [PubMed] [Google Scholar] Flores-Morales A, Stahlberg N, Tollet-Egnell P, Lundeberg J, Malek RL, Quackenbush J, Lee NH, Norstedt G. Microarray analysis of the in vivo effects of hypophysectomy and growth hormone treatment on gene expression in the rat. Endocrinology. 2001;142:3163–3176. [PubMed] [Google Scholar] Rowland JE, Lichanska AM, Kerr LM, White M, d'Aniello EM, Maher SL, Brown R, Teasdale RD, Noakes PG, Waters MJ. In vivo analysis of growth hormone receptor signaling domains and their associated transcripts. Mol Cell Biol. 2005;25:66–77. [PMC free article] [PubMed] [Google Scholar] Huo JS, McEachin RC, Cui TX, Duggal NK, Hai T, States DJ, Schwartz J. Profiles of growth hormone (GH)-regulated genes reveal time-dependent responses and identify a mechanism for regulation of activating transcription factor 3 by GH. J Biol Chem. 2006;281:4132–4141. [PubMed] [Google Scholar] Vidal OM, Merino R, Rico-Bautista E, Fernandez-Perez L, Chia DJ, Woelfle J, Ono M, Lenhard B, Norstedt G, Rotwein P, Flores-Morales A. In vivo transcript profiling and phylogenetic analysis identifies suppressor of cytokine signaling 2 as a direct signal transducer and activator of transcription 5b target in liver. Mol Endocrinol. 2007;21:293–311. [PubMed] [Google Scholar] Clodfelter KH, Holloway MG, Hodor P, Park SH, Ray WJ, Waxman DJ. Sex-dependent liver gene expression is extensive and largely dependent upon signal transducer and activator of transcription 5b (STAT5b): STAT5b-dependent activation of male genes and repression of female genes revealed by microarray analysis. Mol Endocrinol. 2006;20:1333–1351. [PubMed] [Google Scholar] Jorgensen JO, Jessen N, Pedersen SB, Vestergaard E, Gormsen L, Lund SA, Billestrup N. GH receptor signaling in skeletal muscle and adipose tissue in human subjects following exposure to an intravenous GH bolus. Am J Physiol Endocrinol Metab. 2006;291:E899–E905. [PubMed] [Google Scholar] Nielsen C, Gormsen LC, Jessen N, Pedersen SB, Moller N, Lund S, Jorgensen JO. Growth hormone signaling in vivo in human muscle and adipose tissue: impact of insulin, substrate background, and growth hormone receptor blockade. J Clin Endocrinol Metab. 2008;93:2842–2850. [PubMed] [Google Scholar] Waxman DJ, O'Connor C. Growth hormone regulation of sex-dependent liver gene expression. Mol Endocrinol. 2006;20:2613–2629. [PubMed] [Google Scholar] Wauthier V, Waxman DJ. Sex-specific early growth hormone response genes in rat liver. Mol Endocrinol. 2008;22:1962–1974. [PMC free article] [PubMed] [Google Scholar] Ahluwalia A, Clodfelter KH, Waxman DJ. Sexual dimorphism of rat liver gene expression: regulatory role of growth hormone revealed by deoxyribonucleic Acid microarray analysis. Mol Endocrinol. 2004;18:747–760. [PubMed] [Google Scholar] Zhou YC, Waxman DJ. Cross-talk between janus kinase-signal transducer and activator of transcription (JAK-STAT) and peroxisome proliferator-activated receptor-alpha (PPARalpha) signaling pathways. Growth hormone inhibition of pparalpha transcriptional activity mediated by stat5b. J Biol Chem. 1999;274:2672–2681. [PubMed] [Google Scholar] Zhou YC, Waxman DJ. STAT5b down-regulates peroxisome proliferator-activated receptor alpha transcription by inhibition of ligand-independent activation function region-1 transactivation domain. J Biol Chem. 1999;274:29874–29882. [PubMed] [Google Scholar] Ono M, Chia DJ, Merino-Martinez R, Flores-Morales A, Unterman TG, Rotwein P. Signal transducer and activator of transcription (Stat) 5b-mediated inhibition of insulin-like growth factor binding protein-1 gene transcription: a mechanism for repression of gene expression by growth hormone. Mol Endocrinol. 2007;21:1443–1457. [PubMed] [Google Scholar] Murphy LJ. Insulin-like growth factor-binding proteins: functional diversity or redundancy? J Mol Endocrinol. 1998;21:97–107. [PubMed] [Google Scholar] Barthel A, Schmoll D, Unterman TG. FoxO proteins in insulin action and metabolism. Trends Endocrinol Metab. 2005;16:183–189. [PubMed] [Google Scholar] Accili D, Arden KC. FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell. 2004;117:421–426. [PubMed] [Google Scholar] Rotwein P. Contemporary endocrinology: the IGF system. Totowa: Humana Press; 1999. Molecular biology of IGF-I and IGF-II; pp. 19–35. [Google Scholar] Hall LJ, Kajimoto Y, Bichell D, Kim SW, James PL, Counts D, Nixon LJ, Tobin G, Rotwein P. Functional analysis of the rat insulin-like growth factor I gene and identification of an IGF-I gene promoter. DNA Cell Biol. 1992;11:301–313. [PubMed] [Google Scholar] Adamo ML, Ben-Hur H, Roberts CTJ, LeRoith D. Regulation of start site usage in the leader exons of the rat insulin-like growth factor-I gene by development, fasting, and diabetes. Mol Endocrinol. 1991;5:1677–1686. [PubMed] [Google Scholar] Shimatsu A, Rotwein P. Mosaic evolution of the insulin-like growth factors. Organization, sequence, and expression of the rat insulin-like growth factor I gene. J Biol Chem. 1987;262:7894–7900. [PubMed] [Google Scholar] Kim SW, Lajara R, Rotwein P. Structure and function of a human insulin-like growth factor-I gene promoter. Mol Endocrinol. 1991;5:1964–1972. [PubMed] [Google Scholar] Kavsan VM, Koval AP, Grebenjuk VA, Chan SJ, Steiner DF, Roberts CTJ, LeRoith D. Structure of the chum salmon insulin-like growth factor I gene. DNA Cell Biol. 1993;12:729–737. [PubMed] [Google Scholar] Hoyt EC, Van Wyk JJ, Lund PK. Tissue and development specific regulation of a complex family of rat insulin-like growth factor I messenger ribonucleic acids. Mol Endocrinol. 1988;2:1077–1086. [PubMed] [Google Scholar] Woelfle J, Billiard J, Rotwein P. Acute control of insulin-like growth factor-1 gene transcription by growth hormone through STAT5B. J Biol Chem. 2003;278:22696–22702. [PubMed] [Google Scholar] Woelfle J, Chia DJ, Rotwein P. Mechanisms of growth hormone (GH) action. Identification of conserved Stat5 binding sites that mediate GH-induced insulin-like growth factor-I gene activation. J Biol Chem. 2003;278:51261–51266. [PubMed] [Google Scholar] Bichell DP, Kikuchi K, Rotwein P. Growth hormone rapidly activates insulin-like growth factor I gene transcription in vivo. Mol Endocrinol. 1992;6:1899–1908. [PubMed] [Google Scholar] Thomas MJ, Kikuchi K, Bichell DP, Rotwein P. Characterization of deoxyribonucleic acid-protein interactions at a growth hormone-inducible nuclease hypersensitive site in the rat insulin-like growth factor-I gene. Endocrinology. 1995;136:562–569. [PubMed] [Google Scholar] An MR, Lowe WLJ. The major promoter of the rat insulin-like growth factor-I gene binds a protein complex that is required for basal expression. Mol Cell Endocrinol. 1995;114:77–89. [PubMed] [Google Scholar] Mittanck DW, Kim SW, Rotwein P. Essential promoter elements are located within the 5' untranslated region of human insulin-like growth factor-I exon I. Mol Cell Endocrinol. 1997;126:153–163. [PubMed] [Google Scholar] Wang L,Wang X, Adamo ML. Two putative GATA motifs in the proximal exon 1 promoter of the rat insulin-like growth factor I gene regulate basal promoter activity. Endocrinology. 2000;141:1118–1126. [PubMed] [Google Scholar] Wang X, Talamantez JL, Adamo ML. A CACCC box in the proximal exon 2 promoter of the rat insulin-like growth factor I gene is required for basal promoter activity. Endocrinology. 1998;139:1054–1066. [PubMed] [Google Scholar] Wang Y, Jiang H. Identification of a distal STAT5-binding DNA region that may mediate growth hormone regulation of insulin-like growth factor-I gene expression. J Biol Chem. 2005;280:10955–10963. [PubMed] [Google Scholar] Chia DJ, Ono M, Woelfle J, Schlesinger-Massart M, Jiang H, Rotwein P. Characterization of distinct Stat5b binding sites that mediate growth hormone-stimulated IGF-I gene transcription. J Biol Chem. 2006;281:3190–3197. [PubMed] [Google Scholar] Eleswarapu S, Gu Z, Jiang H. Growth hormone regulation of insulin-like growth factor-I gene expression may be mediated by multiple distal signal transducer and activator of transcription 5 binding sites. Endocrinology. 2008;149:2230–2240. [PMC free article] [PubMed] [Google Scholar] Björntorp, P. (1992) Biochemistry of obesity in relation to diabetes. In: KGMM Alberti RA DeFronzo H Keen P Zimmet eds. International Textbook of Diabetes Mellitus 551– 568. John Wiley & Sons Ltd London, United Kingdom. Google Scholar  Björntorp, P. (1992) Hormonal effects on fat distribution and its relationship to health risk factors. Acta Paediatr Suppl 383: 59– 60. CAS PubMed Google Scholar  Rosèn, T., Bosaeus, I., Tolli, J., Lindstedt, G., Bengtsson, BA. (1993) Increased body fat mass and decreased extracellular fluid volume in adults with growth hormone deficiency. Clin Endocrinol (Oxf) 38: 63 Wiley Online Library PubMed Web of Science®Google Scholar  Liu JP, Baker J, Perkins AS, Robertson EJ, Efstratiadis A. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r) Cell. 1993;75:59–72. [PubMed] [Google Scholar] Zhou Y, Xu BC, Maheshwari HG, He L, Reed M, Lozykowski M, Okada S, Cataldo L, Coschigamo K, Wagner TE, Baumann G, Kopchick JJ. A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse) Proc Natl Acad Sci U S A. 1997;94:13215–13220. [PMC free article] [PubMed] [Google Scholar] Sims NA, Clement-Lacroix P, Da Ponte F, Bouali Y, Binart N, Moriggl R, Goffin V, Coschigano K, Gaillard-Kelly M, Kopchick J, Baron R, Kelly PA. Bone homeostasis in growth hormone receptor-null mice is restored by IGF-I but independent of Stat5. J Clin Invest. 2000;106:1095–1103. [PMC free article] [PubMed] [Google Scholar] Yakar S, Rosen CJ, Beamer WG, Ackert-Bicknell CL, Wu Y, Liu JL, Ooi GT, Setser J, Frystyk J, Boisclair YR, LeRoith D. Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest. 2002;110:771–781. [PMC free article] [PubMed] [Google Scholar] Miyakoshi N, Kasukawa Y, Linkhart TA, Baylink DJ, Mohan S. Evidence that anabolic effects of PTH on bone require IGF-I in growing mice. Endocrinology. 2001;142:4349–4356. [PubMed] [Google Scholar] Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;344:1434–1441. [PubMed] [Google Scholar] Ishizuya T, Yokose S, Hori M, Noda T, Suda T, Yoshiki S, Yamaguchi A. Parathyroid hormone exerts disparate effects on osteoblast differentiation depending on exposure time in rat osteoblastic cells. J Clin Invest. 1997;99:2961–2970. [PMC free article] [PubMed] [Google Scholar] McCarthy TL, Centrella M, Canalis E. Parathyroid hormone enhances the transcript and polypeptide levels of insulin-like growth factor I in osteoblast-enriched cultures from fetal rat bone. Endocrinology. 1989;124:1247–1253. [PubMed] [Google Scholar] Zhao G, Monier-Faugere MC, Langub MC, Geng Z, Nakayama T, Pike JW, Chernausek SD, Rosen CJ, Donahue LR, Malluche HH, Fagin JA, Clemens TL. Targeted overexpression of insulin-like growth factor I to osteoblasts of transgenic mice: increased trabecular bone volume without increased osteoblast proliferation. Endocrinology. 2000;141:2674–2682. [PubMed] [Google Scholar] Bengtsson, BÅ, Edén, S., Lönn, L., et al (1993) Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. J Clin Endocrinol Metab 76: 309– 317. Crossref CAS PubMed Web of Science®Google Scholar  Al‐Shoumer, K. A. S., Page, B., Thomas, E., Murphy, M., Beshyah, S. A., Johnston, DG. (1996) Effects of four years’ treatment with biosynthetic human growth hormone (GH) on body composition in GH‐deficient hypopituitary adults. Eur Endocrinol 135: 559– 567. Crossref CAS PubMed Web of Science®Google Scholar  Li, C. H., Simpson, M. E., Evans, HM. (1949) Influence of growth and adrenocorticotropic hormone on the body composition of hypophysectomized rats. Endocrinology 44: 71– 75. Crossref CAS PubMed Web of Science®Google Scholar  Scow, RO. (1959) Effects of growth hormone and thyroxine on growth and chemical composition of muscle, bone and other tissues in thyroidectomized‐hypophysectomized rats. Am J Physiol 196: 859– 865. CAS PubMed Web of Science®Google Scholar  Lee, M. O., Schaffer, NK. (1934) Anterior pituitary growth hormone and the composition of growth. J Nutr 7: 337– 363. Crossref CAS Web of Science®Google Scholar  Goodman, H. M., Schwartz, J. (1974) Growth hormone and lipid metabolism. In: E Enobil WH Sawyer eds. Handbook of Physiology, Part 2 IV: 211– 232. American Physiological Society Washington DC. Google Scholar  Bengtsson, BÅ, Brummer, R. J. M., Edén, S., Rosèn, T., Sjöström, L. (1992) Effects of growth hormone on fat mass and fat distribution. Acta Paediatr Suppl 383: 62– 65. PubMed Google Scholar  Tanner, J. M., Hughes, P. C. R., Whitehouse, RH. (1977) Comparative rapidity of response of height, limb muscle and limb fat to treatment with human growth hormone in patients with and without growth hormone deficiency. Acta Endocrinol (Copenh) 84: 53– 57. Google Scholar  Goodman, H. M., Gorin, E., Honeyman, TW. (1988) Biochemical basis for the lipolytic activity of growth hormone. In: LE Underwood eds. Human Growth Hormone: Progress and Challenges 75– 111. Marcel Dekker Inc New York. Google Scholar  Bonnet, F., Vanderschueren‐Lodeweyckx, M., Echels, R., Malvaux, P. (1974) Subcutaneous adipose tissue and lipids in blood in growth hormone deficiency before and after treatment with human growth hormone. Pediatr Res 8: 800– 805. Crossref CAS PubMed Web of Science®Google Scholar  van Vliet, G, Bosson, D., Craen, M., Caju, NVLD, Malvaux, P., Vanderschueren‐Lodeweyckx, M. (1987) Comparative study of the lipolytic potencies of pituitary‐derived and biosynthetic human growth hormone in hypopituitary children. J Clin Endocrinol Metab 65: 876– 879. Crossref PubMed Web of Science®Google Scholar  Beauville, M., Harent, I., Crampes, F., Riviere, D., Tauber, M. T., Tauber, J. P., Garrigues, M. (1992) Effect of long‐term rhGH administration in GH‐deficient adults on fat cell epinephrine response. Am J Physiol 263: E467– E472. Crossref CAS PubMed Web of Science®Google Scholar  Vernon, R. G., Flint, DJ. (1989) Role of growth hormone in the regulation of adipocyte growth and function. In: RB Heap, C Prosser GE Lamming eds. Biotechnology in Growth Regulation 57– 71. Butterworths London, United Kingdom. Crossref Web of Science®Google Scholar  Harant, I., Beauville, M., Crampes, F., et al (1994) Response of fat cells to growth hormone (GH): effect of long term treatment with recombinant human GH in GH‐deficient adults. J Clin Endocrinol Metab 78: 1392– 1395. Crossref PubMed Web of Science®Google Scholar  Marcus, C., Bolme, P., Micha‐Johansson, G., Margery, V., Brönnegård, M. (1994) Growth hormone increases the lipolytic sensitivity from catecholamines in adipocytes from healthy adults. Life Sci 54: 1335– 1341. Crossref CAS PubMed Web of Science®Google Scholar  Yang, S., Björntorp, P., Liu, X., Edén, S. (1996) Growth hormone treatment of hypophysectomized rats increases catecholamine‐induced lipolysis and the number of β‐adrenergic receptors in adipocytes: no differences in the effects of growth hormone on different fat depots. Obes Res 4: 471– 478. Wiley Online Library CAS PubMed Web of Science®Google Scholar  Watt, P. W., Finley, E., Cork, S., Legg, R. A., Vernon, RG. (1991) Chronic control of the β‐ and α2‐adrenergic systems of sheep adipose tissue by growth hormone and insulin. Biochem J 273: 39– 42. Crossref CAS PubMed Web of Science®Google Scholar  Arner, P. (1992) Adrenergic receptor function in fat cells. Am J Clin Nutr 55: 228S– 236S. Crossref CAS PubMed Web of Science®Google Scholar  Arner, P., Hellmér, J., Wennlund, A., Östman, J., Engfeldt, P. (1988) Adrenoceptor occupancy in isolated human fat cells and its relationship with lipolysis rate. Eur J Pharmacol 146: 45– 56. Crossref CAS PubMed Web of Science®Google Scholar  Davidson, MB. (1987) Effect of growth hormone on carbohydrate and lipid metabolism. Endocr Rev 8: 115– 131. Crossref CAS PubMed Web of Science®Google Scholar  Ottosson, M., Lönnroth, P., Björntorp, Edén S. (2000) Effects of cortisol and growth hormone on lipolysis in human adipose tissue. J Clin Endocrinol Metab 85: 799– 803. Crossref CAS PubMed Web of Science®Google Scholar  Pierlussi, J., Pierlussi, R., Aschcroft, SJH. (1980) Effects of growth hormone on insulin release in the rat. Diabetologia 19: 391– 396. Crossref PubMed Web of Science®Google Scholar  Roupas, P., Ghou, S. T., Towns, R. J., Kostyo, JL. (1991) Growth hormone inhibits activation of phosphatidylinositol phospholipase C in adipose plasma membranes: evidence for a growth hormone‐induced change in G protein function. Physiol Pharmacol 88: 1691– 1695. CAS PubMed Web of Science®Google Scholar  72 Slavin, B. G., Ong, J. M., Kern, P. (1994) Hormonal regulation of hormone‐sensitive lipase activity and mRNA levels in isolated rat adiposities. J Lipid Res 35: 1535– 1541. CAS PubMed Web of Science®Google Scholar  Sheridan, MK. (1986) Effects of thyroxin, cortisol, growth hormone, and prolactin on lipid metabolism of coho salmon, oncorhynchus kisutch, during smoltification. Gen Comp Endocrinol 64: 220– 238. Crossref CAS PubMed Web of Science®Google Scholar  Dietz, J., Schwartz, J. (1991) Microdetermination of long chain fatty acids in plasma and tissue. J Biol Chem 235: 2595– 2599. PubMed Web of Science®Google Scholar Yang, S., Xu, X., Björntorp, P., Edén, S. (1995) Additive effects of growth hormone and testosterone on lipolysis in adipocytes of hypophysectomized rats. J Endocrinol 147: 147– 152. Crossref CAS PubMed Web of Science®Google Scholar  Lands, A. M., Arnold, A., McAuliff, J. P., Bron, TG. (1967) Differentiation of receptor systems activated by sympathetic amines. Nature 214: 597– 598. Crossref CAS PubMed Web of Science®Google Scholar  Stiles, G. L., Caron, M. G., Lefkowitz, RJ. (1984) β‐Adrenergic receptors: biochemical mechanisms of physiological regulation. Physiol Rev 64: 661– 743. Crossref CAS PubMed Web of Science®Google Scholar  Emorine, L. J., Marullo, S., Briend‐Sutren, M. M., et al (1989) Molecular characterization of human β3‐adrenergic receptor. Science 245: 1118– 1121. Crossref CAS PubMed Web of Science®Google Scholar  Ahquist, RP. (1948) A study of the adrenotropic receptors. Am J Physiol 153: 586– 600. PubMed Web of Science®Google Scholar  Honnor, R. C., Dhillon, G. S., Londos, C. (1985) cAMP‐dependent protein kinase and lipolysis in rat adipocytes. I. Cell preparation, manipulation and predictability in behavior. J Biol Chem 260: 15122– 15129. CAS PubMed Web of Science®Google Scholar  Honnor, R. C., Dhillon, G. S., Londos, C. (1985) cAMP‐dependent protein kinase and lipolysis in rat adipocytes. II. Definition of steady‐state relationship with lipolytic and antilipolytic modulators. J Biol Chem 260: 15130– 15138. CAS PubMed Web of Science®Google Scholar  Corbin, J. D., Cobb, C. E., Beebe, S. J., et al (1988) Mechanism and function of cAMP‐ and cGMP‐dependent protein kinases. Adv Second Messenger Phosphoprotein Res 21: 75– 86. CAS PubMed Web of Science®Google Scholar  Londos, C., Brasaemle, D. L., Schultz, C. J., Segrest, J. P., Kimmel, AR. (1999) Perilipins, ADRP, and other proteins that associate with intracellular neutral lipid droplets in animal cells. Semin Cell Dev Biol 10: 51– 58. Crossref CAS PubMed Web of Science®Google Scholar  Holm, C., Osterlund, T., Laurell, H., Contreras, JA. (2000) Molecular mechanisms regulating hormone‐sensitive lipase and lipolysis. Annu Rev Nutr 20: 365– 393. Crossref CAS PubMed Web of Science®Google Scholar  Brasaemle, D. L., Rubin, B., Harten, I. A., Gruia‐Gray, J., Kimmel, A. R., Londos, C. (2000) Perilipin A increases triacylglycerol storage by decreasing the rate of triacylglycerol hydrolysis. J Biol Chem 275: 38486– 38493. Crossref CAS PubMed Web of Science®Google Scholar  Tansey, J. T., Huml, A. M., Vogt, R., et al (2003) Functional studies on native and mutated forms of perilipins. A role in protein kinase A‐mediated lipolysis of triacylglycerols. J Biol Chem 278: 8401– 8406. Crossref CAS PubMed Web of Science®Google Scholar  Strålfors, P., Björgell, P., Belfrage, P. (1984) Hormone regulation of hormone‐sensitive lipase in intact adipocytes: Identification of phosphorylated sites and effects of the phosphorylation by lipolytic hormone and insulin. Proc Natl Acad Sci U S A 81: 3317– 3321. Crossref CAS PubMed Web of Science®Google Scholar  Egan, J. J., Greenberg, A. S., Chang, M. K., Wek, SA Moos JMC, Londos, C. (1992) Mechanism of hormone‐stimulated lipolysis in adipocytes: translocation of hormone‐sensitive lipase to the lipid storage droplet. Proc Natl Acad Sci U S A 89: 8537– 8541. Crossref CAS PubMed Web of Science®Google Scholar  Anthonsen, M. W., Ronnstrand, L., Wernstedt, C., Degerman, E., Holm, C. (1998) Identification of novel phosphorylation sites in hormone‐sensitive lipase that are phosphorylated in response to isoproterenol and govern activation properties in vitro. J Biol Chem 273: 215– 221. Crossref CAS PubMed Web of Science®Google Scholar  Sztalryd, C., Xu, G., Dorward, H., et al (2003) Perilipin A is essential for the translocation of hormone‐sensitive lipase during lipolytic activation. J Cell Boil 161: 1093– 1103. Crossref CAS PubMed Web of Science®Google Scholar  Smith, PE. (1930) Hypophysectomy and replacement therapy in the rat. Am J Anat 45: 205– 273. Wiley Online Library Web of Science®Google Scholar  Edén, S., Jansson, J. O., Oscarsson, J. (1987) Sexual dimorphism of growth hormone secretion. In: O Isaksson C Binder K Hall B Hökfelt eds. Growth Hormone—Basic and Clinical Aspects 129– 151. Elsevier Science Publishers B.V Amsterdam. Google Scholar  Frohman, L. A., Bernardis, LL. (1970) Growth hormone secretion in rat: metabolic clearance and secretion rates. Endocrinology 86: 305– 312. Crossref CAS PubMed Google Scholar  Jansson, J. O., Albertsson‐Wikaland, K., Edén, S., Thorngren, K. G., Isaksson, O. (1982) Circumstantial evidence for a role of the secretory pattern of growth hormone in control of body growth. Acta Endocrinol 99: 24– 30. CAS PubMed Web of Science®Google Scholar  Björntorp, P., Karlsson, M., Pertoft, H., Pettersson, P., Sjöström, L., Smith, U. (1978) Isolation and characterization of cells from rat adipose tissue developing into adipocytes. J Lipid Res 19: 316– 324. CAS PubMed Web of Science®Google Scholar  Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, RJ. (1951) Protein measurements with the folin phenol reagent. J Biol Chem 193: 265– 275. CAS PubMed Web of Science®Google Scholar  Rebuffé‐Scrive, M. (1987) Sex steroid hormones and adipose tissue metabolism in adrenalectomized and ovariectomized rats. Acta Physiol Scand 129: 471– 477. Wiley Online Library CAS PubMed Web of Science®Google Scholar  Laurell, S., Tibbling, G. (1966) An enzymatic fluorometric micromethod for the determination of glycerol. Clin Chim Acta 13: 317– 322. Crossref CAS PubMed Web of Science®Google Scholar  Dole, V. P., Meinertz, H. (1960) Microdetermination of long chain fatty acids in plasma and tissues. J Biol Chem 235: 2595– 2599. CAS PubMed Web of Science®Google Scholar  Smith, U., Sjöström, L., Björntorp, P. (1972) Comparison of two methods of determining human adipose cell size. J Lipid Res 13: 822– 824. CAS PubMed Web of Science®Google Scholar  Östman, J., Arner, P., Kimura, H., Wahrenberg, H., Engfeldt, P. (1984) Influence of fasting on lipolytic response to adrenergic agonists and on adrenergic receptors in subcutaneous adipocytes. Eur J Clin Invest 14: 383– 391. Wiley Online Library PubMed Web of Science®Google Scholar  Steiner, A. L., Pagliara, A. S., Chase, L. R., Kipnis, DM. (1972) Radioimmunoassay for cyclic nucleotides. II. Adenosine 3′, 5′‐monophosphate and guanosine 3′, 5′‐monophosphate in mammalian tissues and body fluids. J Biol Chem 247: 1114– 1120. CAS PubMed Web of Science®Google Scholar  Steiner, A. L., Parker, C. W., Kipnis, DM. (1972) Radioimmunoassay for cyclic nucleotides. I. Preparation of antibodies and iodinated cyclic nucleotides. J Biol Chem 247: 1106– 1113. CAS PubMed Web of Science®Google Scholar  McKenzie, FR. (1988) Basic techniques to study G‐protein function. In: G Milligan eds. Signal Transduction—A Practical Approach, Part 2 31– 56. Oxford University Press New York. Google Scholar  Solomon, S. S., Sibley, S. D., Dismukes, J.R. (1991) Growth hormone‐enhanced lipolysis in the spontaneously diabetic BB rat. J Lab Clin Med 118: 99– 105. CAS PubMed Web of Science®Google Scholar  Nam, S. Y., Marcus, C. (2000) Growth hormone and adipocyte function in obesity. Horm Res 53: (Suppl 1), 87– 97. Crossref CAS PubMed Web of Science®Google Scholar  Bahouth, S. W., Malbon, CC. (1988) Subclassification of β‐adrenergic receptors of rat fat cells: a re‐evaluation. Mol Pharmacol 34: 318– 326. CAS PubMed Web of Science®Google Scholar  Granneman, J. G., Lahners, K. N., Chaudhry, A. (1992) Molecular cloning and expression of the rat β3‐adrenergic receptor. Mol Pharmacol 40: 895– 899. Web of Science®Google Scholar  Hollenga, C. H., Zaagsma, J. (1989) Direct evidence for the atypical nature of functional β‐adrenoceptors in rat adipocytes. Br J Pharmacol 98: 1420– 1424. Wiley Online Library CAS PubMed Web of Science®Google Scholar  Lacasa, D., Agli, B., Giudicelli, Y. (1985) Direct assessment of β‐adrenergic receptors in intact rat adipocytes by binding of [3H]CGP 12177. Eur J Biochem 146: 339– 346. Wiley Online Library CAS PubMed Web of Science®Google Scholar  Umekawa, T., Yoshida, T., Sakane, N., Kondo, M. (1996) Effect of CL316, 243, a highly specific β3‐adrenoceptor agonit, on lipolysis of human and rat adipocytes. Horm Metab Res 28: 394– 396. Crossref CAS PubMed Web of Science®Google Scholar  Bojanic, D., Nahorski, SR. (1983) Identification and subclassification of rat adipocyte β‐adrenoceptors using (±)‐[125I]cyanopindolol. Eur J Pharmacol 93: 235– 243. Crossref CAS PubMed Web of Science®Google Scholar  Langin, D., Portillo, M., Saulnier‐Blache, J. S., Lafontan, M. (1991) Coexistence of three beta‐adrenergic receptor subtypes in white fat cells of various mammalian species. Eur J Pharmacol 199: 291– 301. Crossref CAS PubMed Web of Science®Google Scholar   •••WANT YOUR QUESTION ANSWERED?••• Create a free account at www.theprepcoachforum.com and post up your question in the Mike Arnold PED Q&A open threat!    •••SUPPORT OUR PEPTIDE/RESEARCH CHEMS SPONSORS•••   (RESEARCH CHEMS) www.maresearchchems.net___use discount code “alex15” to save off your order!   (SPECIALTY SUPPS) www.masupps.com___use discount code “alex20” to save off your order!   (BEEF) www.skinnybeef.com___use discount code “alex10” to save off your order!   •••FIND THE EPISODES•••   ITUNES:https://itunes.apple.com/us/podcast/beastfitness-radios-podcast/id1065532968   LIBSYN:http://beastfitnessradio.libsyn.com   VIMEO: www.vimeo.com/theprepcoach        •••PREP COACH APPAREL•••   https://teespring.com/stores/the-prep-coach-apparel    

Guest: Fred R. Hirsch, MD, PhD Here to walk us through our current understanding of oncogene addiction and the resulting progress that’s been made in lung cancer treatment is Dr. Fred Hirsch from Mount Sinai.

Guest: Fred R. Hirsch, MD, PhD Here to walk us through our current understanding of oncogene addiction and the resulting progress that’s been made in lung cancer treatment is Dr. Fred Hirsch from Mount Sinai.

Kimberly was a member of the Dr. Joanna Burdette lab and worked on projects related to the origins of ovarian cancer. She also discusses the learning curve of being a new member of a research lab. Kimberly's citations: Ren, Y., Ribas, H. T., Heath, K., Wu, S., Ren, J., Shriwas, P., & Kinghorn, A. D. (2020). Na+/K+-ATPase-Targeted Cytotoxicity of (+)-Digoxin and Several Semisynthetic Derivatives. Journal of Natural Products, 83(3), 638-648. [link] Hardy, L. R., Pergande, M. R., Esparza, K., Heath, K. N., Önyüksel, H., Cologna, S. M., & Burdette, J. E. (2019). Proteomic analysis reveals a role for PAX8 in peritoneal colonization of high grade serous ovarian cancer that can be targeted with micelle encapsulated thiostrepton. Oncogene, 38(32), 6003-6016. [link] Ren, Y., Tan, Q., Heath, K., Wu, S., Wilson, J. R., Ren, J., ... & Chen, X. (2020). Cytotoxic and non-cytotoxic cardiac glycosides isolated from the combined flowers, leaves, and twigs of Streblus asper. Bioorganic & Medicinal Chemistry, 115301. [link]

Tras un descanso, regresamos con el 1er episodio de la 2ª temporada (grabado el 25-09-19). En este episodio Francis nos comenta un análisis bioinformático publicado en Nature Microbiology que analiza la historia evolutiva de las agrupaciones génicas. Pepe entrevista a Sandra Peiró (VHIO, Barcelona) y comenta el último trabajo de su grupo, publicado en Oncogene, sobre una nueva estrategia terapéutica contra el cáncer de mama triple negativo. Silvana, por su parte, nos resume un interesante estudio comparativo en el que analizan la microbiota de los recién nacidos y nos presenta el libro "Superbacterias" (Editorial Guadalmazán) del microbiólogo José Ramos Vivas (IDIVAL, Santander), a quien entrevistamos en la última parte del episodio. Y, como siempre, nuestros estudiantes preferidos, Belén e Íker nos traen sus entetenidas (bio)noticias. Bienvenidos al octavo episodio de Biosíntesis.

is a groundbreaking look at the role of water in living organisms that ultimately brings us closer to answering the riddle of the etiology of, and therapy and treatment for, cancer. When President Nixon launched the War on Cancer with the signing of the National Cancer Act of 1971 and the allocation of billions of research dollars, it was amidst a flurry of promises that a cure was within reach. The research establishment was trumpeting the discovery of oncogenes, the genes that supposedly cause cancer. As soon as we identified them and treated cancer patients accordingly, cancer would become a thing of the past. Fifty years later it’s clear that the War on Cancer has failed―despite what the cancer industry wants us to believe. New diagnoses have continued to climb; one in three people in the United States can now expect to battle cancer during their lifetime. For the majority of common cancers, the search for oncogenes has not changed the treatment: We’re still treating with the same old triad of removing (surgery), burning out (radiation), or poisoning (chemotherapy). In , Dr. Cowan argues that this failure was inevitable because the oncogene theory is incorrect―or at least incomplete―and based on a flawed concept of biology in which DNA controls our cellular function and therefore our health. Instead, Dr. Cowan tells us, the somatic mutations seen in cancer cells are the result of a cellular deterioration that has little to do with oncogenes, DNA, or even the nucleus. The root cause is metabolic dysfunction that deteriorates the structured water that forms the basis of cytoplasmic―and therefore, cellular―health. Despite mainstream medicine’s failure to bring an end to suffering or deliver on its promises, it remains illegal for physicians to prescribe anything other than the “standard of care” for their cancer patients―no matter how dangerous and ineffective that standard may be―and despite the fact that gentler, more effective, and more promising treatments exist. While Dr. Cowan acknowledges that all of these treatments need more research, is an impassioned plea from a long-time physician that these promising treatments merit our attention and research dollars and that patients have the right to information, options, and medical freedom in matters of their own life and death. Dr. Cowan, MD, is a veteran family physician who has studied and written about many subjects in medicine, including nutrition, homeopathy, anthroposophical medicine, and herbal medicine. He is the author of : A Doctor’s Quest to Understand, Treat, and Prevent Cardiovascular Disease and the new book from Chelsea Green Publishing. He is also a founding board member of the Weston A. Price Foundation, and a frequent lecturer throughout the US and Canada. He's also the same doctor I mentioned in when I talked about how your “heart is not a pump”. He also produces some of the most fantastic vegetable powders in existence, which I use every day: My previous episodes with Dr. Cowan include: - ). - - He also published the fascinating article on my website entitled: - . Dr. Cowan's other excellent books include:   During our discussion, you'll discover: -Whether or not the efficacy of chemotherapy has ever been studied [7:45] President Nixon announced "War on Cancer" in 1971; promised it would be gone within 10 years Early 1990's, German statistician  announces 2.9% of stage 3&4 cancer patients see improvement with chemo Early 2000's, Australian government commissions a study for all stages; Concluded that 2.3-2.4% show improvement Decreased quality of life; marginally longer life expectancy in chemo patients -Why a reduction in tumor size isn't always a good thing [12:00] Any study not involving life expectancy is called a "surrogate study" Reduction in size can result in a compromised immune system which perpetuates the need for chemo -Dr. Cowan's thoughts on the current theories upon which modern cancer treatments are based [15:30] "Oncogene" or "somatic mutation" theory came to light in 1971 Mutation in a somatic chromosome, which drives the cancer Actual results: everyone has different somatic mutations Biotech industry is based on finding problematic mutations, which are impossible to decipher After 40 years of war on cancer, over 95% of treatment has nothing to do with the oncogene theory Oncogenes are not the root cause of cancer when you get right down to it Mutations are a consequence of an improperly functioning cell, not the cause of it When you transfer the nuclei from a cancerous cell to a healthy cell, the healthy cell will not become cancerous; however, if you transfer the cytoplasm from a cancerous cell, the healthy cell will develop cancer - and his contributions to current cancer treatments [25:00] All cancers feel different (rock like) compared to other tissue Cells have a charge around them, and when two similarly charged cells come together, they keep their distance Strength of the charge determines the density of the tissue (why different organs have different textures) Halo of charges come from sodium/potassium gradient Always start with the charge: walk barefoot, swim in the ocean, sunlight, expose to heat and cold, mineral water Sodium/potassium pump is a myth "The contents of the cytoplasm are structured water" -The form of water while it's inside the cytoplasm [35:10] It's gel-like, not the forms we usually think It's a mesh that binds to the potassium in the cell, excludes the sodium, and maintains the sodium/potassium gradient Structured water forms similar to Jello ATP molecule acts as the heat that activates the gel (energy currency) Watery matrix the DNA resides in is what determines which part of the DNA will be expressed The DNA is an expression of an "idea" or a creator, and the "idea" is the water -How the integrity of the DNA and cytoplasm is damaged, thus enabling cancer to form [43:15] Cells lose charge, clump together, form a tumor Aneuploidy: the presence of an abnormal number of chromosomes in a cell Reversing the loss of charge, restoring the cell would be a more efficacious treatment for cancer than radiation, surgery, chemo, etc. Cytoplasm is akin to the birth of Jesus Christ Lourdes healing water (in France) -Gerson Therapy, Quinton and cancer treatment [50:15] "The problem with cancer is the problem of sodium/potassium" Created a juicer that extracts cytoplasm from fruits and veggies Gerson's protocol was based on increasing potassium, reducing sodium Rene Quinton's sea water (natural way of structuring water) is a mineral-rich water put through a vortex -The reason why Dr. Cowan does not treat cancer patients in his practice [57:45] -How plants and mushrooms are used to treat cancer [59:15] Mistletoe is the most used, most successful natural treatment To be injected subcutaneously Mistletoe is not currently available in the U.S. -Whether deuterium-depleted water could be an effective treatment for cancer [1:03:10] Deuterium (D2O) interferes with ability of mitochondria to generate ATP, and has different physical chemical properties from water Dr. Cowan is disappointed w/ the current state of deuterium-depleted water manufacturers "If you have cancer, or might get cancer, you should drink deuterium-depleted water." -Whether oral or IV administration is optimal for Nicotinamide adenine dinucleotide (NAD) [1:10:15] NADH is better than NAD -The value of electronic devices such as the Rife for treating cancer [1:13:30] -How melatonin is used for cancer therapy [1:15:45] -And much more... Resources from this episode:  - Book: - - Study: - Quinton water from (use code GREENFIELD10) - Quinton water from Dr. Slovak's website (use code GREENFIELD for a 10% discount) - - - Melatonin (use code GREENFIELD10) - - - Bone broth recipe: Onions, carrots, greens sautéed in ghee/turmeric mixture Add Add tsp of , , - Ben's previous podcasts and episodes about cancer: - podcast with Dr. David Minkoff - podcast with Eric Remensperger - podcast with Dr. Joshua Axe Episode sponsors: -: My personal playground for new supplement formulations, Kion blends ancestral wisdom with modern science. Ben Greenfield Fitness listeners, receive a 10% discount off your entire order when you use discount code: BGF10. -: A new take on an ancient secret: Pain-soothing herbs, incredible antioxidants, and phytonutrients all in one delicious, soothing “Golden Milk” nighttime tea! Receive a 20% discount on your entire order when you use discount code: BENG20. -: Organic brands you love, for less. Your favorite organic food and products. Fast and free shipping to your doorstep. Receive 25% off your order when you use ! -: Try the shaving company that’s fixing shaving. Get a $13 value trial set that comes with everything you need for a close, comfortable shave when you go to -: Whether you’re an insurance expert or a newbie, Policygenius created a website that makes it easy for you to compare quotes, get advice, and get covered. Do you have questions, thoughts or feedback for Dr. Thomas Cowan or me? Leave your comments below and one of us will reply!

Ahead on Biotechnology Focus radio are some of the stories from universities across the country and their innovative research this week. The University of British Columbia presents research that Alzheimer’s might be a whole-body problem. The University of Guelph identifies key protein in cancer metastasis. A University of Toronto scientist will be conducting a real-time study of astronauts while on mission. And, Western University’s National Centre for Audiology will be testing a device that may lay the foundation for hearing in the future. Welcome to another episode of Biotechnology Focus radio. I am your host, Michelle Currie, here to give you a run-down of the top stories of Canada’s biotech scene.  Our first story this week takes us to British Columbia, where recent studies are showing that Alzheimer’s might be linked to more than just deteriorating brain matter and plaque. It could be a whole-body phenomenon. The findings that were published in Molecular Psychiatry offer hope that future drug therapies might be able to stop or slow the disease without acting directly on the brain. Instead, the drugs might be able to target areas such as the liver and kidney to flush out the toxic proteins that cause dementia before ever reaching the brain. Weihong Song, a psychiatry professor from the university of British Columbia and Yan-Jiang Wang, a neurology professor at the Third Military Medical University in Chongqing, China, demonstrated the mobility of a protein linked to Alzheimer’s disease through a technique called parabiosis. The technique involves surgically attaching two specimens together so they share the same blood supply for several months. The scientists attached normal mice, which don’t naturally develop Alzheimer’s disease, with mice modified to carry a mutant human gene that produces elevated levels of the protein called amyloid beta. In people with Alzheimer’s disease, that protein ultimately forms clumps, or “plaque”. The findings described the mice who had been attached to an amyloid beta inflicted counterpart ended up “contracting” the disease, all in just a few months. Not only did the normal mice develop plaque, but also a “tangle”-like pathology, which are twisted protein strands that form inside brain cells that disrupt their function to eventually kill them from the inside-out. Other signs of Alzheimer’s-like damage included brain cell degeneration, inflammation, and microbleeds. Even the ability to transmit electrical signals involved in learning and memory were impaired after a brief time being joined. Amyloid beta is produced in other areas of the body besides the brain. It can be found in blood platelets, blood vessels, and muscles. Until these experiments, it was unclear if amyloid beta from outside the brain could contribute to Alzheimer’s disease. It appears from this study, that indeed it can. Perhaps in the near future, researchers and scientists will develop a drug that would tag the amyloid beta biochemically in such a way that the liver or kidney will be able to flush it out before generating damage. +++++++ The University of Guelph researchers have made a discovery during one of their ground-breaking studies. They have identified a protein known as cadherin-22 that binds cancer cells together and allows them to invade tissues. Hindering this protein showed signs of reduction in metastatic cancer patients for breast and brain cancer cells by up to 90 per cent. This study was published in the journal Oncogene and looks specifically at hypoxia in tumours. More solid cancer tumours that are depleted of oxygen, are difficult to treat and replicate at a faster rate. The researchers from the university discovered from the analysis of more than 100 patients with breast or brain cancer that there was a link between the quantity of cadherin-22 and the level of hypoxia in a tumour itself. The more hypoxic the tumour was, the higher the protein count of cadherin-22. Until now, little was known about how oxygen-deprived cancer cells bound together and interacted to spread. The U of G researchers found that it is precisely under conditions of low oxygen that cancer cells trigger the production of cadherin-22, putting in motion a kind of protein boost that helps bind cells together, enhancing cellular movement, invasion, and likely metastasis. The protein is found on the outside of cells and allows hypoxic cancer cells to migrate together. Scientists have known for decades that hypoxia plays a role in tumour growth and metastasis, as well as a poor patient outcome. Professor Jim Uniacke and his team identified that cadherin-22 plays an integral part in the advancement of cancer cells. The researchers used an incubator to monitor cancer cells in a low-oxygen environment comparable to a tumour, where the protein cadherin-22 had been removed via molecular tools. The cancer cells failed to spread. These findings offer vital insights into the aggression and migration of cancer cells. +++++++ A University of Toronto scientist will be performing real-time blood cell analyses on astronauts to reveal how time, space, and speed affect the immune system. Dr. Chen Wang hopes that this research will lead to an understanding of how stress and other environmental factors impact our ability to fight disease. Wang, a professor in the faculty of medicine’s department of laboratory medicine and pathobiology and a clinician-scientist at Mount Sinai Hospital, will be leading the project named Immuno Profile, to study the astronauts on the International Space Station over the course of five years. Canadian astronaut and physician, David Saint-Jacques, will be part of the next mission to the space station and will participate in several Canadian-made health experiments announced by the Canadian Space Agency. The astronauts will use a device that will take finger-prick blood samples during the flight mission, then the information will be sent back to Wang and his team for analysis. Wang expects to see immune cell and cytokine mediator changes, identify different types of immune cells and to see if the cells are functioning well or not. Wang also commented on the uniqueness of the space flight environment to study immune system stressors. Immune dysfunction relates to many diseases, including cancers, viral infections, MS, type I diabetes, and even the aging process. The weightlessness of space can also be used to learn more about the less-understood lymphatic system, which depends on the pressure to flow properly. They hope to develop a new model for how the immune system responds to circadian rhythm and various stresses. +++++++ Lastly for this week, Western University’s National Centre for Audiology (NCA) is testing a new device that may lay the foundation for the hearing of the future. Recently approved by Health Canada and already available in the states, Earlens hearing aid offers a remarkable chance for the hearing impaired to listen in to the everyday world. Its sound-to-light technology eliminates the whistling noise common in conventional hearing aids and delivers the broadest frequency on the market that results in a more life-like sound with crisp highs and rumbling lows. Western University is the first Canadian location authorized to test out the Earlens hearing aid and see if it measures up. Traditional hearing aids are worn behind the ear or in the ear and pick-up, amplify and process incoming sounds and direct them into the ear canal. Meanwhile, the Earlens rests directly on the eardrum and gently activates the natural hearing system. Western’s National Centre for Audiology is a state-of-the-art research centre. It has developed national protocols for pediatric heating assessments, developed methods for fitting hearing aids, has tested numerous devices for more than a dozen companies across the globe and is dedicated to tackling complex issues related to hearing loss. The NCA will be testing the Earlens device using a double-blind study to examine if its light pulse invention turns on the bulb to resonate a way to the future of hearing. ++++++++ Well that wraps up another episode of Biotechnology Radio. We hope you enjoyed it. If you have any feedback or story ideas, please reach out to us via press@promotivemedia.ca. From all of us here at Biotechnology Focus, have a wonderful week ahead. From my desk to yours – this is Michelle Currie.

Hosts: Vincent Racaniello, Alan Dove, Rich Condit, and Kathy Spindler Guest: Mark Fuccio The TWiVome reveal the first eukaryotic genes found in a bacteriophage of Wolbachia, and how DNA tumor virus oncogenes antagonize sensing of cytoplasmic DNA by the cell.   Become a patron of TWiV! Links for this episode Zika virus in vaginal secretions (EID) Zika virus in semen (EID) Eukaryotic genes in a bacteriophage (Nat Commun) Seth Bordenstein on TWiV 332 DNA tumor virus oncogenes antagonize cGAS-STING (Science) Letters read on TWiV 412 This episode is brought to you by CuriosityStream, a subscription streaming service that offers over 1,400 documentaries and non­fiction series from the world's best filmmakers. Get unlimited access starting at just $2.99 a month, and for our audience, the first two months are completely free if you sign up at curiositystream.com/microbe and use the promo code MICROBE. This episode is also brought to you by Drobo, a family of safe, expandable, yet simple to use storage arrays. Drobos are designed to protect your important data forever. Visit www.drobo.com to learn more. Listeners can save $100 on a Drobo system at drobostore.com by using the discount code Microbe100. Weekly Science Picks Mark - EFN Enterprise Futures Network and Mission Log Podcast Alan - 2016 Wildlife Comedy Photography Rich -  ZuTA, portable robotic printerKathy - How LEGO help blind people see Vincent - Airplane photos of Mike Kelley Listener Pick Hannah - Frozen Flow Glass (Instagram) Send your virology questions and comments to twiv@microbe.tv

Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Rich Condit, and Kathy Spindler Guest: Harold Varmus The TWiV team is together in New York City for a conversation with Nobel Laureate Harold Varmus about his remarkable career in science.   Become a patron of TWiV! Links for this episode Varmus Laboratory Varmus and Kandel on Charlie Rose (transcript) Rescuing biomedical research Letters read on TWiV 400 Video of this episode at YouTube This episode is sponsored by CuriosityStream. Get two months free when you sign up at curiositystream.com/microbe and use the promo code MICROBE. This episode was made possible by PLoS Pathogens - the leading Open Access journal to publish breakthroughs in understanding pathogens and their interactions with host organisms and each other. PLOS Pathogens fosters the open exchange of ideas across fields, publishing original research on viruses, bacteria, fungi, parasites, and prions. For more information, check out www.plospathogens.org Weekly Science Picks Alan - A year on EarthRich - TWiV #1: West Nile Virus Dickson - Chasing storms, chasing beautyKathy - Bioartography and FASEB image and video competitionVincent - The Art and Politics of Science by Harold Varmus (free download) Listener Picks Trudy - Scientific Studies on Last Week Tonight with John Oliver Send your virology questions and comments to twiv@microbe.tv

The amazing advances made in mapping the human genome don’t alter one longstanding fact: when it comes to unlocking the scientific secrets of life, fruit flies rule. Uptal Banerjee, Chair of the the Department of Molecular, Cell and Developmental Biology at UCLA, explains that most principles that have been laid out in developmental biology — from mechanisms of stem cell maintenance to how a head differs from a tail — came from work in Drosophila. Series: "UCLA Faculty Research Lectures" [Science] [Show ID: 30565]

The amazing advances made in mapping the human genome don’t alter one longstanding fact: when it comes to unlocking the scientific secrets of life, fruit flies rule. Uptal Banerjee, Chair of the the Department of Molecular, Cell and Developmental Biology at UCLA, explains that most principles that have been laid out in developmental biology — from mechanisms of stem cell maintenance to how a head differs from a tail — came from work in Drosophila. Series: "UCLA Faculty Research Lectures" [Science] [Show ID: 30565]

Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Rich Condit, and Kathy Spindler The TWiVniks consider the role of a cell enzyme that removes a protein linked to the 5'-end of the picornavirus genome, and the connection between malaria, Epstein-Barr virus, and endemic Burkitt's lymphoma.   Links for this episode Divergent requirements for removing VPg (mBio) Bond, covalent bond (TWiV 210) Link between malaria and endemic Burkitt's lymphoma (PLoS Path) Multifactorial role of malaria in Burkitt's lymphoma (PLoS Path) Plasmodium infection promotes AID-dependent B cell lymphoma (Cell) Children's cancer dependent on climatic factors (Nature) Denis Burkitt (Wikipedia) Request for PACE trial data (virology blog) Letters read on TWiV 374 This episode is sponsored by 32nd Clinical Virology Symposium and ASM Grant Writing Webinar Weekly Science Picks Alan - Indoor skydivingVincent - Cancer Virus by Crawford, Johannessen, and RickinsonRich - WitKathy - The Only Woman in the Room by Eileen PollackDickson - Show everyone your clinical data Send your virology questions and comments to twiv@microbe.tv

Vincent, Dickson, and Daniel discuss how a secreted protein from the protozoan parasite Theileria transforms its host cells via a cellular proto-oncogene. Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin Links for this episode: Leishmania (TWiP #14) Transformation by a prolyl isomerase (Nature) Theileria.org Prolyl isomerase (Wikipedia) Image from Transformation & Oncogenesis Letters read on TWiP 88 Contact Send your questions and comments (email or mp3 file) to twip@twiv.tv Subscribe Subscribe to TWiP (free) in iTunes, by the RSS feed or by email

Winning the war?: In 1971, the then president of the United States, Richard Nixon, declared ‘war’ on cancer. Since then, billions of dollars have been poured into cancer research worldwide, but a cure for the disease is still a long way off. In this Nature Video, reporter Lorna Stewart marks the scientific milestones of the past four decades. She explores cancer genetics with Nobel laureate Michael Bishop, vaccines with fellow laureate Harald zur Hausen, and two young researchers tell Lorna about some of cancer research’s greatest success stories.

In this podcast, I will discuss first-line usage of anti-EGFR therapies in metastatic colorectal cancer in the context of the PEAK trial findings with a focus on the emerging data surrounding RAS oncogene mutations in treatment selection.

Professor Xin Lu talks about the links between cancer and regenerative medicine. Professor Xin Lu is the Director of the Oxford branch of the Ludwig Institute for Cancer Research. Her lab works toward identifying molecular mechanisms that suppress tumour growth and metastasis and focuses on understanding the factors that lead to uncontrollable cell growth.

Professor Xin Lu talks about the links between cancer and regenerative medicine. Identifying the switches that turn cell growth off and on would have profound implications for cancer medicine. If the right mechanisms can be found, cancer cells could be targeted specifically, resulting in more efficient treatments. Professor Xin Lu is working to identify the molecular mechanisms that naturally suppress tumour growth. Nuclear reprogramming could also enable cells to be utilized more safely and effectively in regenerative medicine.

Professor Xin Lu talks about the links between cancer and regenerative medicine. Identifying the switches that turn cell growth off and on would have profound implications for cancer medicine. If the right mechanisms can be found, cancer cells could be targeted specifically, resulting in more efficient treatments. Professor Xin Lu is working to identify the molecular mechanisms that naturally suppress tumour growth. Nuclear reprogramming could also enable cells to be utilized more safely and effectively in regenerative medicine.

Professor Xin Lu talks about the links between cancer and regenerative medicine. Professor Xin Lu is the Director of the Oxford branch of the Ludwig Institute for Cancer Research. Her lab works toward identifying molecular mechanisms that suppress tumour growth and metastasis and focuses on understanding the factors that lead to uncontrollable cell growth.

How does cancer spread? How can we target our immune system to take out tumours? This week we visit the National Cancer Research Institute's annual conference to explore the cutting edge of cancer research. We'll find out why cancers become resistant to chemotherapy, and how new research offers us a window to watch a cancer as it spreads. Like this podcast? Please help us by supporting the Naked Scientists

How does cancer spread? How can we target our immune system to take out tumours? This week we visit the National Cancer Research Institute's annual conference to explore the cutting edge of cancer research. We'll find out why cancers become resistant to chemotherapy, and how new research offers us a window to watch a cancer as it spreads. Like this podcast? Please help us by supporting the Naked Scientists

A growth signal can mediate feedback that reduces cell proliferation and stem cell self-renewal.

Vincent, Dickson, Rich, and Alan answer listener questions about XMRV, cytomegalovirus, latency, shingles vaccine, myxomavirus and rabbits, and more.

Silvano Riva, Institute for Biochemical and Evolutionary Genetics/CNR, Pavia, Italy speaks on "Role of alternative splicing of the RON proto-oncogene mRNA in epithelian-mesenchimal transition (EMT) and metastasis". This seminar has been recorded at ICTP Trieste by ICGEB

Deregulation of the cell cycle regulator cyclin D1 in a wide variety of tumors has highlighted the role of cell cycle alterations in cancer. Genomic amplifications, mutations or balanced chromosomal translocations involving this gene are believed to lead to its aberrant overexpression in tumors. Somatic mutations in the 3’UTR of cyclin D1 gene have been reported in breast cancer, neuroblastoma and mantle cell lymphoma patients although their contribution to the cyclin D1 deregulation is unclear. In our study, we confirmed a regulatory role of the 3’UTR in cyclin D1 expression. Our results demonstrated that deletion of the cyclin D1 3’UTR significantly alters cyclin D1 protein expression and function. Similarly, the introduction of mutations observed in MCL patients in the cyclin D1 3’UTR significantly increased the expression of the cyclin D1 protein. These results underline that in malignancies such as MCL, truncation of the 3’UTR due to genomic deletions or somatic mutations is a likely cause of cyclin D1 overexpression. In order to ascertain whether the deletion of the cyclin D1 3’UTR could impart proliferative properties to cells, thereby contributing to transformation, we assessed the phenotype of fibroblasts retrovirally transduced with cyclin D1 with or without the 3’UTR. Interestingly our results demonstrated marked changes in cyclin D1 function upon deletion of the cyclin D1 3’UTR. Cells expressing cyclin D1 without the 3’UTR proliferated significantly more than those expressing the full length cyclin D1. Similar results were observed in rat ileum epithelial cells which lack the endogenous cyclin D1. Thus our data confirm that the deletion of the 3’UTR confers a proliferative advantage to cells. Furthermore, in this dissertation, we focused on the different potential regulatory elements of the cyclin D1 3’UTR to assess their role in controlling cyclin D1 expression. We reasoned that elements in the 3’UTR that are responsible for the controlled expression of the cyclin D1 protein are lost in 3’UTR deleted tumors. Therefore, it would be interesting to specifically pinpoint the role of these elements and highlight their contribution to cyclin D1 protein expression. It is assumed that since AU-rich elements (AREs) in the 3’UTR of cyclin D1 could have a potential destabilizing effect on the cyclin D1 mRNA, their loss could contribute to the observed overexpression of cyclin D1. Importantly, using highly sensitive reporter assays, we showed that the targeted loss of AREs from an otherwise intact 3’UTR leads to a decrease in reporter expression. These results demonstrate that the loss of these cis-acting elements in 3’UTR deleted tumors cannot account for cyclin D1 overexpression and there must be additional factors involved. Using bioinformatic analysis, we identified putative binding sites for microRNAs, small regulatory non-coding RNAs that have been shown to have important roles in cancer. Our study confirmed that microRNAs of the miR-15/16 family and the miR-17-92 cluster directly target the cyclin D1 gene through post-transcriptional regulation. These microRNAs have been shown to be involved in a cell cycle regulation and in a number of malignancies, especially in B-cell lymphoma. The various forms of cyclin D1 generated by deletions or mutations in the 3”UTR of cyclin D1 in tumors exclude these microRNA binding sites. Taken together, our results demonstrate a regulatory role for the 3’UTR in cyclin D1 expression and function. We show that the deletion of the cyclin D1 3’UTR leads to cyclin D1 overexpression and confers a proliferative advantage to cells. Finally, our results characterize the regulators functions of the different cis and trans-acting elements of the cyclin D1 3’UTR and identify this region as a bona fide target of cell cycle regulatory microRNAs. Extending these findings to other oncogenes, it is conceivable that the escape of 3’UTR mediated regulation by the acquisition of additional mutations of this region is an under-appreciated mechanism in the pathogenesis of cancer.

Overexpression of proto-oncogene c-jun and constitutive activation of the Jun NH2-terminal kinase (JNK) signaling pathway have been implicated in the leukemic transformation process. However, c-jun expression has not been investigated in acute myeloid leukemia (AML) cells containing the most common chromosomal translocations. t(8;21) is one of the most common AML-associated translocation and results in the AML1-ETO fusion protein. Overexpression of AML1-ETO in NIH3T3 cells leads to increased phosphorylation of Ser63 in c-Jun, which is generally JNK dependent. The role of the JNK signaling pathway for the functional properties of AML1-ETO is, however, unknown. In the present study we found high expression levels of c-jun mRNA in t(8;21), t(15;17) or inv(16) positive patient cells by microarray analysis. Within t(8;21) positive patient samples, there was a correlation between AML1-ETO and c-jun mRNA expression levels. In myeloid U937 cells, c-jun mRNA and c-Jun protein expression levels increased upon induction of AML1-ETO. AML1-ETO transactivated the human c-jun promoter through the proximal AP-1 site via activating the JNK signaling pathway. JNK targets c-Jun and ATF-2, which also bind to the proximal AP-1 site in U937 cells, were also phosphorylated upon AML1-ETO induction. Furthermore, AML1-ETO induction increased the DNA binding capacity of c-Jun and ATF-2 to the proximal AP-1 site of the c-jun promoter, which might result in their enhanced transactivation capacities. Interference with JNK and c-Jun activation by using JIP-1 or a JNK inhibitor reduced the transactivation capacity of AML1-ETO on the c-jun promoter and the pro-apoptotic function of AML1-ETO in U937 cells. AML1-ETO seems to activate the JNK signaling pathway by inducing the expression of a cytoplasmic factor, possibly G-CSF, because supernatant of AML1-ETO expressing cells was sufficient to induce phosphorylation of JNK and c-Jun in wildtype U937 cells. This data demonstrates a novel mechanism of how AML1-ETO might exert positive effects on target gene expression and identifies the proto-oncogene c-jun as a common target gene in AML patient cells.

Alterations in oncogenes are critical steps in the development of endometrial cancer. To investigate the potential clinical relevance of the amplification of the oncogenes c-erbB2, c-myc, and int-2 and the mutation of K-ras in endometrial cancer, 112 tumors were examined using PCR-based fluorescent DNA technology. Amplification of the three oncogenes and the mutation of K-ras were correlated with age, tumor size, lymph node status, metastases, stage, histological types, grade, steroid hormone receptor expression (estrogen receptor, ER; progesterone receptor, PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy. Oncogene amplification of c-erbB2 was detected in 18.9%, of c-myc in 2.7% and of int-2 in 4.2%, and K-ras mutation in 11.6%. No significant correlations could be detected between amplification of c-erbB2 and any of the other parameters. Mutation of K-ras is associated with positive expression of PgR. This might indicate that mutation and activation of K-ras are involved in the development of hormonal independence in endometrial cancer.

Más información de este acto