Podcasts about akt1

Featuring an interview with Dr Rinath M Jesselsohn, including the following topics: Imlunestrant with or without abemaciclib in advanced breast cancer: Results of the Phase III EMBER-3 trial (0:00) Jhaveri KL et al. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med 2025;392(12):1189-202. Abstract  Jhaveri KL et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy & combined with abemaciclib, for patients with ER+, HER2- advanced breast cancer (ABC), pretreated with endocrine therapy (ET): Results of the Phase 3 EMBER-3 trial. San Antonio Breast Cancer Symposium 2024;Abstract GS1-01. Comprehensive genomic profiling of ESR1, PIK3CA, AKT1 and PTEN in HR-positive, HER2-negative metastatic breast cancer: Prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice (7:00) Bhave MA et al. Comprehensive genomic profiling of ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(-) metastatic breast cancer: Prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice. Breast Cancer Res Treat 2024;207(3):599-609. Abstract Camizestrant, a next-generation oral selective estrogen receptor degrader (SERD), versus fulvestrant for postmenopausal women with estrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): A multi-dose, open-label, randomized, Phase II trial (10:25) Oliveira M et al. Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): A multi-dose, open-label, randomised, phase 2 trial. Lancet Oncol 2024;25(11):1424-39. Abstract Latest on SERDs: An education session at San Antonio Breast Cancer Symposium 2024 (13:57) Jeselsohn RM. Latest on selective estrogen receptor degraders (SERDs). San Antonio Breast Cancer Symposium 2024;Education Session 5. CME information and select publications

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

In this JCO Article Insights episode, Giselle de Souza Carvalho provides a summary on  "Navigating Treatment Pathways in Metastatic Hormone Receptor–Positive, HER2-Negative Breast Cancer: Optimizing Second-Line Endocrine and Targeted Therapies" by Bhardwarj, et al and "US Food and Drug Administration Approval Summary: Capivasertib With Fulvestrant for Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Locally Advanced or Metastatic Breast Cancer With PIK3CA/AKT1/PTEN Alterations" by Dilawari et al published in the Journal of Clinical Oncology.  TRANSCRIPT Giselle Carvalho: Hello and welcome to JCO Article Insights episode for the December issue of the Journal of Clinical Oncology. I'm your host Giselle Carvalho, Medical Oncologist in Brazil focusing on breast cancer and melanoma skin cancers and one of the ASCO Editorial Fellows at JCO this year. Today, I will be discussing two articles. The first one is “Navigating Treatment Pathways in Metastatic Hormone Receptor–Positive, HER2-Negative Breast Cancer: Optimizing Second-Line Endocrine and Targeted Therapies,” and the second one is the “US FDA Approval Summary on Capivasertib with Fulvestrant  for HR-positive HER2-negative Locally Advanced or Metastatic Breast Cancer with PIK3CA/AKT1/PTEN Alteration.”  As we know, 65% to 70% of all breast cancers are HR-positive HER2-negative and this is also the most common subtype of metastatic breast cancer. The current standard of care for frontline therapy of patients with luminal metastatic disease is a CDK4/6 inhibitor in combination with endocrine therapy. However, as new endocrine and targeted therapies gain approval, choosing the best systemic therapy upon disease progression after frontline therapy is a topic of ongoing debate. Nearly 40 to 50% of HR-positive breast cancers have actionable genomic alterations and molecular testing should be a routine recommendation for patients with metastatic HR-positive HER2-negative disease. This can be performed repeating tissue biopsy at the time of progression or from archival tissue. Treatment options after progression on CDK4/6 inhibitors include alpelisib in combination with fulvestrant in patients with PIK3CA mutant tumors as seen in the SOLAR-1 trial, or capivasertib with fulvestrant in patients with a tumor mutation in (PI3K)–AKT–PTEN pathway as seen in the CAPItello-291 study, which will be discussed further.  In approximately 30% of patients, progression on frontline endocrine plus CDK4/6 inhibitor treatment is caused by endocrine resistance, frequently involving activating mutations in ESR1. For those tumors, elacestrant, an oral SERD is an option as demonstrated in the EMERALD trial. For patients with a BRCA mutation, PARP inhibitors represent another option. If no mutations are detected, everolimus, an mTOR inhibitor, can be used based on the BOLERO-2 results. The phase 2 MAINTAIN and PACE trials, along with the phase 3 postMONARCH trial support changing the endocrine therapy backbone with or without switching the CDK4/6 inhibitor. In less resourced areas, fulvestrant monotherapy is still an option to delay cytotoxic chemotherapy, though its efficacy is limited when used as a single agent. Finally, after progression on at least one line of chemotherapy, antibody drug conjugates including sacituzumab govitecan or trastuzumab deruxtecan may be an option.  Now focusing on the PI3K AKT PTEN signaling pathway, activating mutations in PIK3CA and AKT1 and inactivating alterations in PTEN occur in approximately half of luminal breast cancers. In June 2023, the CAPItello-291 trial was published and treatment with fulvestrant plus capivasertib, a PTEN AKT inhibitor, demonstrated a 3.6 month PFS benefit compared to fulvestrant alone, regardless of the presence of AKT pathway alterations. However, for those with tumors without AKT pathway alteration, an exploratory analysis showed that although there was a numerical improvement in PFS, it did not meet statistical significance, indicating that the biomarker positive population primarily drove the positive results noted in the overall population. Therefore, capivasertib plus fulvestrant was approved by the US FDA in November 2023 exclusively for patients with PI3K/AKT1/PTEN tumor alterations after progression on an aromatized inhibitor with or without a CDK4/6 inhibitor. The approved schedule of capivasertib is slightly different from that of other agents used in breast cancer. It is 400 milligrams taken orally twice a day for four days per week every week in a 28-day cycle in combination with fulvestrant. Diarrhea, rash and hyperglycemia were the most commonly reported grade three or four adverse events in the interventional group. I would like to highlight that even though the CAPItello trial excluded patients with glycosylated hemoglobin levels higher than 8% or those diagnosed with diabetes who required insulin, hyperglycemia occurred in 19% of biomarker positive patients treated with capivasertib, with nearly 2% of this population experiencing grade 3 or 4 hyperglycemia and some patients experiencing life threatening outcomes such as diabetic ketoacidosis.  By way of comparison, hyperglycemia of any grade was three times higher with alpelisib therapy in the SOLAR-1 trial, occurring in 64% of the patients and grade three or higher hyperglycemia was seen in 37% of the patients. Diarrhea was the most common treatment related adverse event experienced by 77% of the biomarker positive population. Prompt use of the antidiarrheal drugs when needed, such as loperamide must be encouraged as untreated diarrhea can lead to dehydration and renal injury. Cutaneous rash occurred in 56% of the biomarker positive population in the interventional group and 15% experienced a grade 3 or 4 rash. Nearly half of the patients with cutaneous adverse reactions required treatment and this was the leading reason for dose reduction of capivasertib.  In the biomarker positive population, the improvement in medium PFS were 4.3 months by investigator assessment. Overall survival data from the CAPItello-291 trial is still immature, but quality of life data was recently published in September this year and was assessed by the 30 item QLQ C30 questionnaire and the QLQ BR23, the breast module. According to Oliveira et al, global health status and quality of life were maintained for a longer period with capivasertib fulvestrant than with placebo fulvestrant except for symptoms of diarrhea which were significantly worse in the capivasertib group. The median time of deterioration of global health status and quality of life was twice as long in the capivasertib group being almost 25 months versus 12 months in the placebo fulvestrant group. These data reinforced the use of capivasertib in combination with fulvestrant for the treatment of HR-positive HER2-negative advanced breast cancer patients with PIK3CA/AKT1/PTEN tumor alterations who have progressed after an aromatase inhibitor-based therapy with or without a CDK4/6 inhibitor.  Thank you for listening to JCO Article Insights. This is Giselle Carvalho. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts. See you next time.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.  

Dr. Angela DeMichele, Dr. Lynn Henry, and Dr. Harold Burstein present the latest breast cancer rapid recommendation update impacting two ASCO guidelines. This update focuses on the new option, capivasertib plus fulvestrant, for patients with hormone receptor-positive, HER2-negative metastatic breast cancer with activating PIK3CA or AKT1 mutations or inactivating alterations in PTEN based on data from the recent CAPItello-291 trial. They discuss the updated recommendations on lines of endocrine treatment and selecting between the options for patients with activating PIK3CA mutations. Additionally, we discuss implications for clinicians and patients, and what ongoing research is occurring in the field. Read the latest update, “Endocrine and Targeted Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer – Capivasertib-Fulvestrant: ASCO Rapid Guideline Update“ at www.asco.org/breast-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/breast-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.24.00248 Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.   My name is Brittany Harvey, and today I am interviewing Dr. Harold Burstein from Dana-Farber Cancer Institute, Dr. Angela DeMichele from the University of Pennsylvania, and Dr. Lynn Henry from the University of Michigan, co-chairs on “Endocrine and Targeted Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Capivasertib–Fulvestrant: ASCO Rapid Guideline Update.” Thank you for being here, Dr. Burstein, Dr. DeMichele, and Dr. Henry. Dr. Harold Burstein: We're happy to be here.  Brittany Harvey: And before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including our guests on this episode today, are available online with the publication of the guideline update in the Journal of Clinical Oncology, which is linked in the show notes.  So then, to kick us off, Dr. Burstein, could you first describe what prompted this rapid update, which provides updated recommendations for two ASCO guidelines: the biomarkers for systemic therapy in metastatic breast cancer guideline, and the endocrine treatment and targeted therapy for hormone receptor-positive, HER2-negative metastatic breast cancer guideline? Dr. Harold Burstein: Thanks, Brittany. Well, this team has been working, as you mentioned, actually, on two guidelines, which are clearly evolving in parallel and kind of converging, actually, when you look at data, as we'll be talking about in the next few minutes. The particular catalyst here was a large randomized clinical trial which looked at a new targeted therapy in the space of estrogen receptor-positive, HER2-negative breast cancer. That drug is capivasertib. And the trial was the so-called CAPItello study. In that trial, patients who were receiving second-line therapy with fulvestrant were randomized to that treatment alone, or that plus capivasertib. So the data from that study were the first strong signal that we needed to update the guideline because they were important clinical data.   The other strong signal was that the drug was tested in a cohort of patients who had a specific set of mutations in their cancers. And that included PIK3CA mutations, a class of mutations for which we already had a targeted drug. But it also included some new potential targets, including mutations in the AKT gene itself, capivasertib is an AKT inhibitor, as well as loss of PTEN protein functionality, which potentially sensitizes tumors to the targeted action of this drug as well. So while we had a couple of guidelines catching up on the endocrine therapy space, which is increasingly looking like a targeted therapy space, it was clear that this major study, which had clinical and diagnostic implications, would sort of push them together and served as the impetus for updating both guidelines at the same time. Brittany Harvey: Understood. I appreciate that background information.   So then, Dr. DeMichele, based on this updated data that Dr. Burstein just described, what is the updated recommendation from the guideline panel regarding lines of endocrine treatment? Dr. Angela DeMichele: Well, I think this is where the biomarker evolution that Dr. Burstein just referred to really comes in because now we have the opportunity to perform genomic testing in patients who have ER-positive, HER2-negative metastatic breast cancer, on either the tumor or commonly from the blood. And we can now start to tailor treatment to the specific genomic abnormalities that that patient's tumor contains. So now our guideline really marries both the genomic abnormality with the therapeutic option. First-line treatment remains endocrine therapy plus a CDK 4/6 inhibitor. But things then really start to diverge once we enter second and third-line therapy because at that point, we now have the option to test for several genomic markers: ESR1 mutations, PIK3CA mutations, AKT1 mutations, and PTEN inactivation. And based on whether the tumor has one or any of those mutations, we can then select the therapy based on that.  So in the case of capivasertib, as you just heard, that is a therapy for patients whose tumors have PIK3CA mutations or activating mutations in AKT1 or loss of PTEN. But other patients who don't have one of those mutations may, in the second line, go on to another drug. For example, if they have an ESR1 mutation, they then may be eligible to take elacestrant. Patients who have no targetable mutations still have a targeted option in that they can use everolimus. And in all of these settings, the endocrine therapy partner for this line of therapy is typically fulvestrant. So now we're really starting to tailor therapy in the second- and third-line based on genomic changes. Brittany Harvey: Excellent. That information is helpful for choosing optimal therapy tailored to the individual patients, as you just described.  So then, Dr. Henry, what guidance does the expert panel provide regarding choosing a PIK3CA targeted option? Dr. Lynn Henry: Thank you. So for patients whose tumors are found to have an activating mutation in PIK3CA, we now have two drug options: either alpelisib or capivasertib in combination with fulvestrant. And the problem is, these drugs have not been compared head-to-head. We can't say that one is clearly better than the other, either in terms of efficacy or in terms of side effect profile. What we do have is information from two separate trials in which they were each tested against placebo. The efficacy appears to be fairly similar based on the data that we have. It does appear that the side effect profiles may be slightly different. And so, when you have a patient sitting in front of you and you're trying to decide how best to treat her, you really have to think about, what symptoms does my patient already have? What is she more or less likely to tolerate? So what we do know is that it appears that the rates of grade 3 diarrhea and rash were slightly higher with capivasertib. It looks like hyperglycemia was higher with alpelisib, as was treatment discontinuation. So really you have to make an individualized decision when you have a patient sitting in front of you about which drug you'd like to try. Of course, if someone doesn't tolerate one drug, you can always switch to the other one.  Brittany Harvey: I appreciate that analysis and to provide guidance without a head-to-head trial and to specifically provide options based on an individual patient's profile.   So then, Dr. DeMichele, what should clinicians know as they implement these new recommendations?  Dr. Angela DeMichele: Well, first of all, I think most clinicians now are becoming more familiar with the procedures required for doing genomic testing. But this is something that now has become the standard of care. And so, it is incumbent upon all of us who treat these patients to understand what the options for genomic testing are for that patient, which companies offer this testing, how to send a sample, and how to interpret the report that comes back. So, I think this has really added a level of complexity to the therapy for patients. I also think that one can't simply apply an algorithm to a patient. We have to really treat the whole patient and we have to take into consideration, as Dr. Henry said, the toxicities of these agents and the cost which is also a major issue. So I think that while it is more complex, really that doctor-patient relationship is so important in communicating what these genomic tests mean for a patient and for their options, and also important for the clinician to really understand what the different therapeutic agents might mean for a patient, and really try to pick the agent that's best for that patient. Using genomic testing is just one of several different features that they'll consider. Brittany Harvey: Absolutely. It's key to obtain the data needed to select appropriate patients and to recognize the complexity.   So then, Dr. Henry, in your view, how will this update impact patients with metastatic breast cancer? Dr. Lynn Henry: Yes, so as we've discussed, I think this is really exciting. Over the last few years, we have had quite a number of new medications that have become available for patients and have been FDA-approved. And so this is yet the latest in a series. For those patients whose tumors have a PIK3CA mutation, as we discussed, there are now two options. So you have a choice depending on which one is better covered by insurance, by which one you may tolerate better. But I think the other thing is now, although it's a smaller subset of patients, there are patients out there whose tumors have mutations in AKT1 or alterations in PTEN, and so there's an entirely new endocrine therapy-based option available for them that wasn't available before. So I think that thinking about the new data that are out there, the new drugs that are out there, really is exciting because there are new options available and hopefully there are more to come as well.    Brittany Harvey: Absolutely. It's great to have these new options.  So, finally, Dr. Burstein, Dr. Henry just mentioned what's to come. Could you touch on what some of the outstanding questions are regarding endocrine therapy for patients with metastatic breast cancer?  Dr. Harold Burstein: A couple of things to say. First, ER-positive metastatic breast cancer is the most common kind of metastatic breast cancer, roughly three quarters of metastatic cases of breast cancer will be hormone receptor-positive cancers. So this is a very big public health issue around the world, actually, breast cancer being the number one most commonly diagnosed cancer of women around the world. So minor or major improvements in treatment for advanced ER-positive breast cancer really have a tremendous impact.  The second thing is it's been remarkable to see the progress in the past decade. We've gone from simply targeting the hormonal access itself with medicines like tamoxifen or aromatase inhibitors or an injectable selective estrogen receptor degrader like fulvestrant to incorporating targeted therapies at the same time. And this whole class of drugs called CDK4/6 inhibitors has emerged which we use in either first- or in second-line therapy. Those drugs have transformed our standard of care, improved survival for patients with advanced ER-positive disease, now with median survival nearly 50% longer than what we had seen in the past.  And if you've heard, we have a wealth of opportunities. We can target PIK3CA, we can target ESR1 mutations. Other drugs emerging in the space include PROTACs which is another way of degrading the estrogen receptor. And so there's going to be more progress in the years to come.   So one of the biggest challenges has been to try and understand, is there really an optimal way to use these drugs, or can we be smarter about the particular sequence of all these particular things that are happening.  So one example of this was a recent study that is on a drug, not as yet FDA-approved, called inavolisib, which is a PIK3CA targeted drug used in first line in combination with a CDK4/6 inhibitor and endocrine therapy. And that study, for a high-risk group of women with ER-positive metastatic disease, actually showed a dramatic improvement in overall survival, asking the question if combining some of these targeted therapies together might yet further improve outcomes.  And as you've heard from the diagnostic space, one of the other interesting things is that tumors evolve over time. And so acquisition of the estrogen receptor mutations, ESR1 mutations, which are typically not found early in the course of advanced breast cancer but otherwise later, now have targeted treatments. So there's a whole bunch of stuff going on all at the same time, including multiple ways of targeting things, serial testing to look for acquisition of ESR1 mutations and new pathways to explore. It's an embarrassment of riches in some respects because it has meant it's actually really hard to write a guideline as you've heard, which says, “Do this first, do this second, and do this third.” I suppose that's a good problem to have under the circumstances, but it's going to require really thoughtful clinical trials and careful analysis to help guide specific lines of treatment recommendations like that.  Brittany Harvey: Excellent. We'll look forward to these exciting, continuing developments for patients with metastatic breast cancer. And I want to thank you all so much for your work to develop this rapid recommendation update for these two guidelines. And thank you for taking the time on this podcast today. Dr. Harold Burstein: Thanks. Dr. Lynn Henry: Thank you so much.  Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in the Apple App Store or the Google Play Store. If you have enjoyed what you heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.      

In this discussion with Dr. Hope Rugo, we covered her study Capitello-291, which led to the approval of Capivasertib in hormone receptor-positive breast cancer with AKT1, PTEN, and PIK3CA mutations, which are seen in 40-50% of the cases. We touched base on sequencing of this therapy, and important clinical pearls around the side effect management associated with this drug.

This episode features an interview with Carlos Doti, MD, Vice President, US Medical Affairs Oncology, AstraZeneca, about new breast cancer treatments.Dr. Doti is a hematologist by training and is passionate about developing treatments that have a real impact for people living with cancer across every aspect of their disease. Dr. Doti has worked in industry for the last 14 years, including seven years at AstraZeneca in various roles, and in small markets like Argentina as well as larger global markets. Since 2022, Dr. Doti has been focusing on the US market in hematology and oncology, working in breast, lung, GI and gynecological cancers among others.Dr. Doti has previously served in medical affairs roles at Novo Nordisk A/S and Pfizer. His work is supported by more than 70 congress presentations and several peer-reviewed publications. He has also served as an investigator in more than 25 clinical trials in hemostasis, onco-hematology and infectious disease.Recently, AstraZeneca won approval for the company's AKT inhibitor Truqap (capivasertib) in combination with Faslodex (fulvestrant) for the treatment of hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1, or PTEN). The approval of Truqap was the first-in-class approval for AstraZeneca.Tune into the episode to hear more about the milestone approval of the new combination breast cancer treatment, which has been a much-needed treatment option for the nearly 50 percent of patients with advanced HR-positive breast cancer who have PIK3CA and AKT1 mutations or PTEN alterations, and experience resistance to first-line treatments such as endocrine therapies and CDK 4/6 inhibitors. For more life science and medical device content, visit the Xtalks Vitals homepage.Follow Us on Social MediaTwitter: @Xtalks Instagram: @Xtalks Facebook: https://www.facebook.com/Xtalks.Webinars/ LinkedIn: https://www.linkedin.com/company/xtalks-webconferences YouTube: https://www.youtube.com/c/XtalksWebinars/featured

Recently, the FDA granted approval to capivasertib in combination with fulvestrant for patients with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alterations. In this interview, Editorial Board member Dr. Jason Mouabbi speaks with Dr. Carlos Doti, Head of Medical Affairs, US Oncology at AstraZeneca, about the significance of the approval, its dosing schedule, AstraZeneca's approach towards patient education and adverse event management, and the future of capivasertib in different treatment settings.

Dr Gradishar discusses the FDA approval of capivasertib plus fulvestrant for patients with advanced HR-positive, HER2-negative breast cancer harboring PIK3CA, AKT1, or PTEN alterations.

In our last installment from Lethal Weapons TX, Chris speaks with Blair of AKT1 Sport and Tyler from Resilient Suppressors about the ins and outs of their particular businesses. You can find out more about their companies here at the links below. https://akt1sport.com/and https://resilientsuppressors.com/As always you can listen to our podcast on your favorite podcast app!This is brought to you by https://www.btogear.com/

In this episode of the Hart2Heart Podcast, Dr. Mike Hart is joined by genomics expert Kevin McKernan. The duo delve deep into the complex world of cannabis and psilocybin, discussing THC use in teenagers and schizophrenics, the benefits of CBD, the comparative impacts of cannabis and cigarette smoke, and the potential of THC as a safer option than alcohol. The conversation touches on the carcinogenic risks associated with THC acetate, the importance of product regulation, the potential benefits of cannabinoids for various age groups, and the effects of CBN and other cannabinoids on sleep. Kevin also shares information on a compound ten times more potent than CBD for treating anxiety and schizophrenia. The episode takes a significant turn to discuss vaccine lot variations, the potential risks of repeated mRNA vaccinations, and the importance of not creating more fear around vaccines. Lastly, McKernan enlightens listeners on the health benefits of mycelium, a component of mushrooms. Time-Codes:00:00 - Kevin McKernan introduces his background in genomics, sharing his contributions to the human genome project and his current work on genomic tools for cannabis and psilocybin.03:18 - McKernan tackles the controversial topic of THC use in teenagers and schizophrenics, discussing the biased narrative often presented by government agencies.07:10 - McKernan delves into the AKT1 variant, explaining how it can cause paranoia and other adverse effects in certain individuals when using THC.09:30 - A discussion ensues on the pattern of developing hyperemesis syndrome due to consistent, high THC use, especially with concentrated forms like dab pens.10:30 - Dr. Hart touches on the benefits of CBD for teenagers, particularly for controlling epilepsy and improving mood disorders.12:27 - The potential benefits and risks of THC use among teenagers are explored, with McKernan suggesting it may be a safer alternative to alcohol.16:13 - McKernan discusses a study comparing cannabis and cigarette smoke, shedding light on the anti-inflammatory nature of cannabinoids.18:02 - Carcinogenic risks associated with THC acetate are discussed, underlining the importance of proper regulation and testing for vaping products.24:05 - Dr. Hart discusses Israel's prominent position in cannabis research and CBD's protective effect against concussions.29:36 - McKernan shares a study revealing a compound with tenfold potency compared to CBD for treating anxiety and schizophrenia, implying a lower dose could be equally effective.32:58 - The importance of THCV for weight management is discussed, particularly in the context of the COVID-19 pandemic.34:20 - Dr. Hart shares the benefits of CBD for pain control, especially for inflammation and muscle spasms.36:10 - McKernan talks about the effects of CBN and its potential role in aiding sleep.44:22 - The conversation shifts to psilocybin and its potential for treating depression, citing a recent study comparing it to escitalopram.54:46 - The importance of consuming mycelium in adaptogenic mushrooms for their potential health benefits is discussed.

Featuring perspectives from Dr Komal Jhaveri, including the following topics: •      Case: A premenopausal woman in her early 40s with a 5.8-cm, ER/PR-positive, HER2-negative infiltrating lobular carcinoma and microscopic sentinel node involvement — Arielle Heeke, MD (11:58) •      Case: A premenopausal woman in her early 40s with a 3.1-cm ER/PR-positive, HER2-negative localized invasive ductal carcinoma (IDC) and a Recurrence Score® of 18 — Alan B Astrow, MD (14:51) •      Case: A woman in her late 50s with ER/PR-positive, HER2-negative, microsatellite stable, BRCA1/2 wild-type, metastatic IDC with PALB2 mutation who receives palbociclib/letrozole and zoledronic acid — Shaachi Gupta, MD, MPH (19:37) •      Case: A postmenopausal woman in her early 60s with de novo ER/PR-positive, HER2-low (IHC 1+) metastatic IDC after disease progression on abemaciclib/letrozole and alpelisib/fulvestrant — Zanetta S Lamar, MD (29:32) •      Case: A premenopausal woman in her mid 30s with ER/PR-positive, HER2-negative IDC receiving neoadjuvant chemotherapy and goserelin, now with sexual dysfunction — Laila Agrawal, MD (34:48) •      Case: A woman in her mid 60s with ER/PR-positive, HER2-low bone-only metastatic IDC on endocrine therapy alone since 2001, now experiencing asymptomatic disease progression (ESR1 variant, AKT1 mutation on liquid biopsy) — Philip L Brooks, MD (45:55) CME information and select publications

I en lille podcastserie på fem afsnit dykker vi ned i tilblivelsen af MENS SOLEN BRÆNDER: En co-produktion mellem AKT1 og Sort/Hvid. I dette afsnit kan du høre astrofysiker Anja Cetti Andersen og kulturkritiker Sigrid Adamsson. De så en lille bid af forestillingen kort inden premieren i november og taler om, hvad de har set, og hvordan man også kan se forestillingen fra et videnskabeligt perspektiv. Og hvilket blik er det vigtigste? Det følelsesmæssige eller det videnskabelige? Lyt med. MENS SOLEN BRÆNDER havde premiere den 18. november og spiller indtil den 10. december 2022 på Sort/Hvid i Kødbyen i København. Find billetter på teaterbilletter.dk eller sort-hvid.dk Podcasten er produceret af Felix Thorsen Katzenelson, Laurits Jongejan og Clara Lindstrøm Gleerup. Stort tak til Novo Nordisk Fonden for at gøre forestillingen og podcasten muligt.

I en lille podcastserie på fem afsnit dykker vi ned i tilblivelsen af MENS SOLEN BRÆNDER: En co-produktion mellem AKT1 og Sort/Hvid. I dette afsnit kan du høre Peder Frederik Jensen og Marie Bjørn tale om deres arbejde med manuskriptet til forestillingen: de helt store opgør og de helt små samtaler. Og en samtale om, hvorvidt vi kan leve uden elektricitet? Lyt med. MENS SOLEN BRÆNDER havde premiere den 18. november og spiller indtil den 10. december 2022 på Sort/Hvid i Kødbyen i København. Find billetter på teaterbilletter.dk eller sort-hvid.dk Podcasten er produceret af Felix Thorsen Katzenelson, Laurits Jongejan og Clara Lindstrøm Gleerup. Stort tak til Novo Nordisk Fonden for at gøre forestillingen og podcasten muligt.

I en lille podcastserie på fem afsnit dykker vi ned i tilblivelsen af MENS SOLEN BRÆNDER: En co-produktion mellem AKT1 og Sort/Hvid. I dette afsnit kan du høre Lise Marie Birch (scenograf) og Rasmus Juncker (komponist og lyddesigner)fortælle om deres arbejde med tilblivelsen af det visuelle og auditive univers bag MENS SOLEN BRÆNDER. Vi talte med dem netop, som scenografien skulle indtages af skuespillerne. MENS SOLEN BRÆNDER har premiere den 18. november og spiller indtil den 10. december 2022 på Sort/Hvid i Kødbyen i København. Find billetter på teaterbilletter.dk eller sort-hvid.dk Podcasten er produceret af Felix Thorsen Katzenelson, Laurits Jongejan og Clara Lindstrøm Gleerup. Stort tak til Novo Nordisk Fonden for at gøre forestillingen og podcasten muligt.

I en lille podcastserie på fem afsnit dykker vi ned i tilblivelsen af MENS SOLEN BRÆNDER: En co-produktion mellem AKT1 og Sort/Hvid. I dette afsnit kan du høre Ida Marie Hede og Ursula Andkjær Olsen tale om deres arbejde med manuskriptet til forestillingen. Det handler om teenageoprør, dødsenergier og måske bumser med materie. Lyt med. MENS SOLEN BRÆNDER har premiere den 18. november og spiller indtil den 10. december 2022 på Sort/Hvid i Kødbyen i København. Find billetter på teaterbilletter.dk eller sort-hvid.dk Podcasten er produceret af Felix Thorsen Katzenelson, Laurits Jongejan og Clara Lindstrøm Gleerup. Stort tak til Novo Nordisk Fonden for at gøre forestillingen og podcasten muligt.

Alting er forbundet i kredsløb. Økologiske, økonomiske, kosmiske kredsløb. Vand stiger op på den ene side af kloden og falder som regn på den anden. Af jord er du kommet, til jord skal du blive. d. 18 november har den vildtvoksende musikforestilling ‘MENS SOLEN BRÆNDER' premiere på teater Sort/Hvid. Forestillingen handler om kredsløb og er blevet til i mødet mellem fire forskere og fire forfattere, der omsætter videnskabens pointer til ét samlet teatermanuskript. For hvordan forvandler vi videnskabelige erkendelser om verden til fortællestof, til dramatik, til teater? I denne udgave podcast vil forfatter og dramatiker Ida Marie Hede i samtale med teaterinstruktør Niels Erling fortælle om sit bidrag til deres kommende forestilling om verdens skrøbelige kredsløb – et bidrag, som hun har udviklet i dialog med videnskabsfilosof Rasmus Grønfeldt Winther. ‘MENS SOLEN BRÆNDER' er en musikforestilling af AKT1, som får premiere på teatret Sort/Hvid i København i efteråret 2022. Forestillingen bliver til på baggrund af forskningsinspireret kunstneriske udvikling med følgende præmis: Fire forfattere møder fire forskere og omsætter de videnskabelige pointer til bidrag til et teatermanuskript. Foruden Ida Marie Hede bidrager Ursula Andkjær Olsen, Kaspar Colling Nielsen og Peder Frederik Jensen til 'MENS SOLEN BRÆNDER' i samarbejde med en astrofysiker, en biolog og en geolog. Præsenteres i samarbejde med AKT1 – Danmarks lydteater og Sort/Hvid.

I en lille podcastserie på fem afsnit dykker vi ned i tilblivelsen af MENS SOLEN BRÆNDER: En co-produktion mellem AKT1 og Sort/Hvid. I dette afsnit kan du høre instruktør/idé-person Niels Erling og skuespiller/idé-person i samtale med Felix Thorsen Katzenelson om, hvordan tanken til denne forestilling opstod, og hvilket univers de ønsker at drage publikum ind i. MENS SOLEN BRÆNDER har premiere den 18. november og spiller indtil den 10. december 2022 på Sort/Hvid i Kødbyen i København. Find billetter på teaterbilletter.dk eller sort-hvid.dk Podcasten er produceret af Felix Thorsen Katzenelson, Laurits Jongejan og Clara Lindstrøm Gleerup. Stort tak til Novo Nordisk Fonden for at gøre forestillingen og podcasten muligt.

Growing evidence fruit may lower type 2 diabetes risk Research has found eating at least two serves of fruit daily has been linked with 36% lower odds of developing type 2 diabetes Edith Cowan University (Australia), June 2, 2021 Eating at least two serves of fruit daily has been linked with 36 percent lower odds of developing type 2 diabetes, a new Edith Cowan University (ECU) study has found.  The study, published today in the Journal of Clinical Endocrinology and Metabolism, revealed that people who ate at least two serves of fruit per day had higher measures of insulin sensitivity than those who ate less than half a serve.  Type 2 diabetes is a growing public health concern with an estimated 451 million people worldwide living with the condition. A further 374 million people are at increased risk of developing type 2 diabetes. The study's lead author, Dr Nicola Bondonno from ECU's Institute for Nutrition Research, said the findings offer fresh evidence for the health benefits of fruit.  "We found an association between fruit intake and markers of insulin sensitivity, suggesting that people who consumed more fruit had to produce less insulin to lower their blood glucose levels," said Dr Bondonno.  "This is important because high levels of circulating insulin (hyperinsulinemia) can damage blood vessels and are related not only to diabetes, but also to high blood pressure, obesity, and heart disease. "A healthy diet and lifestyle, which includes the consumption of whole fruits, is a great strategy to lower your risk of developing type 2 diabetes." Fresh is best The study examined data from 7,675 Australians participating in the Baker Heart and Diabetes Institute's AusDiab Study and assessed fruit and fruit juice intake and the prevalence of diabetes after five years. Dr Bondonno said they did not observe the same beneficial relationship for fruit juice.  "Higher insulin sensitivity and a lower risk of diabetes was only observed for people who consumed whole fruit, not fruit juice," she said.  "This is likely because juice tends to be much higher in sugar and lower in fibre."  Dr Bondonno said that it's still unclear exactly how fruit contributes to insulin sensitivity, but it is likely to be multifaceted.  "As well as being high in vitamins and minerals, fruits are a great source of phytochemicals which may increase insulin sensitivity, and fibre which helps regulate the release of sugar into the blood and also helps people feel fuller for longer," she said. "Furthermore, most fruits typically have a low glycaemic index, which means the fruit's sugar is digested and absorbed into the body more slowly."  The study builds on Dr Bondonno's research into the health benefits of fruit and vegetables, particularly those that contain a key nutrient known as flavonoids. The research is part of ECU's Institute of Nutrition Research.     Ginkgo biloba leaves have multicomponent and multitarget synergistic effects on treatment of neurodegenerative diseases Jiangsu Kanion Pharmaceutical Co (China), June 1, 2021 According to news reporting out of Jiangsu, People's Republic of China, research stated, “Ginkgo biloba L. leaves (GBLs), as widely used plant extract sources, significantly improve cognitive, learning and memory function in patients with dementia. However, few studies have been conducted on the specific mechanism of Neurodegenerative diseases (NDs).” Our news journalists obtained a quote from the research from Jiangsu Kanion Pharmaceutical Co. Ltd., “In this study, network pharmacology was employed to elucidate potential mechanism of GBLs in the treatment of NDs. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to obtain the chemical components in accordance with the screening principles of oral availability and drug-like property. Potential targets of GBLs were integrated with disease targets, and intersection targets were exactly the potential action targets of GBLs for treating NDs; these key targets were enriched and analyzed by the protein protein interaction (PPI) analysis and molecular docking verification. Key genes were ultimately used to find the biological pathway and explain the therapeutic mechanism by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Twenty-seven active components of GBLs may affect biological processes such as oxidative reactions and activate transcription factor activities. These components may also affect 120 metabolic pathways, such as the PI3K/AKT pathway, by regulating 147 targets, including AKT1, ALB, HSP90AA1, PTGS2, MMP9, EGFR and APP. By using the software iGEMDOCK, the main target proteins were found to bind well to the main active components of GBLs.” According to the news editors, the research concluded: “GBLs have the characteristics of multi-component and multi-target synergistic effect on the treatment of NDs, which preliminarily predicted its possible molecular mechanism of action, and provided the basis for the follow-up study.” This research has been peer-reviewed.     Diets that promote inflammation could increase breast cancer risk Analysis of dietary patterns for over 350,000 women suggests eating more anti-inflammatory foods helps lower risk Catalan Institute of Oncology and Biomedical Research Institute (Spain) June 7, 2021  A new study of more than 350,000 women found that women with diets incorporating more foods that increase inflammation in the body had a 12% increase in their risk of breast cancer compared to women who consume more anti-inflammatory diets. The new findings are being presented at NUTRITION 2021 LIVE ONLINE.  The study authors found that moving from a more anti-inflammatory diet toward one that increases inflammation upped breast cancer risk in an almost linear manner. Foods that increase inflammation include red and processed meat; high-fat foods such as butter, margarines and frying fats; and sweets including sugar, honey and foods high in sugar. Fruits, vegetables, legumes, tea and coffee all have potentially anti-inflammatory properties. "Most studies examining diet and breast cancer risk have focused on single nutrients or foods rather than the whole diet," said the study's first author Carlota Castro-Espin, a predoctoral fellow at the Catalan Institute of Oncology and Bellvitge Biomedical Research Institute in Barcelona, Spain. "People consume food not nutrients, thus examining overall dietary patterns, rather than single components of diets can lead to more accurate conclusions when analysing associations with a health outcome such as breast cancer."  The new results are based on data from the European Investigation into Cancer and Nutrition (EPIC) study, a prospective study that recruited more than 500,000 participants across 10 European countries starting in the mid-1990s. The study included more than 13,000 breast cancer diagnoses during approximately 15 years of follow-up.  The typical diet for EPIC participants was measured for a year using food frequency or diet history questionnaires. The researchers used this information to calculate an inflammatory score for each study participant based on their intake of 27 foods.  The researchers examined dietary patterns linked with inflammation because long-term, low grade inflammation has been linked with the development of breast cancer. The large number of women in the study allowed the researchers to take a more nuanced look at the relationship between dietary patterns and breast cancer risk.  Their analysis showed that the increase in breast cancer risk due to pro-inflammatory diets appears to be more pronounced among premenopausal women. They also found that the association did not vary by breast cancer hormone receptor subtypes.  "Our results add more evidence of the role that dietary patterns play in the prevention of breast cancer," said Castro-Espin. "With further confirmation, these findings could help inform dietary recommendations aimed at lowering cancer risk."  As a next step, the researchers plan to evaluate the association of the inflammatory potential of diet and other dietary patterns with breast cancer survival using participants in the EPIC study.      Emerging impact of quercetin in the treatment of prostate cancer Shahid Beheshti University of Medical Sciences (Iran), June 3, 2021   According to news originating from Tehran, Iran, research stated, “Quercetin is a flavonoid agent detected in fruits and vegetables with anti-inflammatory, antioxidant, and anticancer effects. This flavonoid can suppress cell cycle transition and induce apoptosis in neoplastic cells.” Our news reporters obtained a quote from the research from Shahid Beheshti University of Medical Sciences: “Therapeutic effects of quercetin have been assessed in diverse cancers including prostate cancer through the establishment of in vitro and in vivo experiments. Moreover, this agent might prevent the initiation of this type of cancer as it indirectly blocks the activity of promoters of two important genes in the pathogenesis of prostate cancer i.e. androgen receptor (AR) and prostate specific antigen (PSA). Several in vitro investigations have identified the differential influence of quercetin on normal prostate cells versus neoplastic cells, emphasizing its specific cytotoxic effects on cancerous cells. The most appreciated route of quercetin effect on prostate cancer cells is the detachment of Bax from Bcl-xL and the stimulation of caspase families. Besides, quercetin might enhance the effects of other therapeutic options against prostate cancer. For instance, a combination of TNF-related apoptosis-inducing ligand (TRAIL) and quercetin has been recommended as a novel modality for the treatment of prostate cancer.” According to the news editors, the research concluded: “These kinds of strategies might overcome resistance to apoptosis in cancer cells. In the current paper, we summarize the recent data about the preventive and therapeutic influences of quercetin in prostate cancer.”     Breast microbiome modified by diet, fish oil Wake Forest School of Medicine, June 4 2021.    Findings reported on June 3, 2021 in Cancer Research add evidence to the effects of diet on the breast's microbiome, the community of microorganisms that exists in breast tissue.  “We have recently demonstrated that dietary patterns modulate mammary microbiota populations,” wrote David R. Soto-Pantoja and colleagues. “An important and largely open question is whether the microbiome of the gut and mammary gland mediates the dietary effects on breast cancer.” To help answer this question, the researchers fed a high fat or a control diet to mice that are susceptible to developing breast cancer. Animals that received the high fat diet had a greater number of tumors, more rapid tumor growth and larger tumor size than those that received the control diet.  Next, mice that were given high fat diets received fecal transplants from mice that received control diets, and control diet-fed animals received transplants from high fat diet-fed animals. The team found that animals that received the control diet developed as many tumors as mice that received the high fat diet.   In a double-blind trial, breast cancer patients were given fish oil supplements or a placebo for two to four weeks prior to surgical removal of their tumors. The researchers observed a change in the microbiota of tumor and normal breast tissue in participants who received fish oil, including an increase in Lactobacilli (which has been associated with reduce breast cancer tumor growth in animals) in normal tumor-adjacent breast tissue of participants who received fish oil for four weeks.  "Obesity, typically associated with a high-fat diet consumption, is a well-known risk factor in postmenopausal breast cancer," commented coauthor Katherine L. Cook, PhD, of Wake Forest University. "This study provides additional evidence that diet plays a critical role in shaping the gut and breast microbiome."     Self-administered aroma foot massage may reduce symptoms of anxiety   Okayama University (Japan), June 8, 2021  Researchers at Okayama University conduct the first community-based study on the effects of self-administered aromatherapy foot massage on stress and anxiety symptoms. The results suggest aromatherapy massages might provide an inexpensive, simple way of managing anxiety.   The continuing popularity of complementary therapies, such as aromatherapy and massage, has prompted scientists to investigate the effects of such therapies on the body in more detail. Complementary therapies are said to reduce the symptoms associated with stress and anxiety, and therefore may reduce the chances of severe illness, such as hypertension and heart disease. The precise effects on the body following such therapies is unclear, however.   Previous studies have focused on the effects of massage and aromatherapy treatments on blood pressure and mental state in hospitalized patients in Japan, but none have been conducted on individuals living in the community. Now, Eri Eguchi and co-workers at Okayama University, together with researchers across Japan, have conducted the first study into the effect of aromatherapy-based foot massage on blood pressure, anxiety and health-related quality of life in people living in the community.   57 participants took part in the study; 52 women and 5 men. Baseline blood pressure and heart rate values were taken at the start and end of the four-week trial period, as well as at a follow-up session 8 weeks later. Participants also completed questionnaires on anxiety status and health-related quality of life at each stage of the trial. The participants were divided into two groups, and one group were taught to perform a 45-minute aromatherapy-based foot massage on themselves three times a week for four weeks.   The results suggest that aroma foot massage decreased the participants' average blood pressure readings, and state of anxiety, and tended to increased mental health-related quality of life score. However the effect of massages was not significant with changes in other factors such as physical health-related quality of life scores and heart rate.   In their paper published in March 2016 in PLOS One, Eguchi's team are cautiously optimistic about the potential for self-administered massage to reduce anxiety in the population: "[although] it was difficult to differentiate the effects of the aromatherapy from the effects of the massage therapy... [the combination] may be an effective way to increase mental health and improve blood pressure."     Aromatherapy and massage Aromatherapy has long been used to relieve stress and anxiety in populations across the globe. Different aroma essential oils are said to have different properties, and are used to induce relaxation and promote well-being. Trials have indicated that certain essential oils, when inhaled, can reduce blood pressure levels and alleviate depression by stimulating the olfactory system. Massage (in its many forms) also has a long history in therapeutic medicine, and the practice of manipulating key pressure points in the body to induce relaxation has been shown to improve mental and physical health. However, detailed scientific studies of the effects of aromatherapy foot massage – an increasingly popular treatment in Japan – on blood pressure and perceived quality of life are limited.   Significance and further work While the trial carried out by Eguchi and her team is limited in some respects, their results provide an initial starting point from which to extend studies into the benefits of aroma foot massage for the general population. Their findings that massage, or the aromatherapy, or a combination of both, reduce blood pressurereadings (at least in the short term) warrants further investigation. Eguchi and her team acknowledge that their decision to advertise for participants may have encouraged more health-conscious and pro-active people to apply. They also received far more applications from women than men, although their age-range (from 27 to 72) was diverse. Further work is needed to determine the effect of aroma foot massage on specific age and sex categories, for example, before such interventions are encouraged in the wider population.     Proteomics reveals how exercise increases the efficiency of muscle energy production University of Copenhagen (Denmark), May 27, 2021 Mitochondria are the cell's power plants and produce the majority of a cell's energy needs through an electrochemical process called electron transport chain coupled to another process known as oxidative phosphorylation. A number of different proteins in mitochondria facilitate these processes, but it's not fully understood how these proteins are arranged inside mitochondria and the factors that can influence their arrangement. Now, scientists at the University of Copenhagen have used state-of-the-art proteomics technology to shine new light on how mitochondrial proteins gather into electron transport chain complexes, and further into so-called supercomplexes. The research, which is published in Cell Reports, also examined how this process is influenced by exercise training.  "This study has allowed for a comprehensive quantification of electron transport chain proteins within supercomplexes and how they respond to exercise training. These data have implications for how exercise improves the efficiency of energy production in muscle," says Associate Professor Atul S. Deshmukh from the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen.  Traditional methods provide too little detail It is already well established that exercise training stimulates mitochondrial mass and affects the formation of supercomplexes, which allows mitochondria in skeletal muscle to produce energy more efficiently. But questions remain about which complexes cluster into supercomplexes and how. To better understand supercomplex formation, particularly in response to exercise, the team of scientists studied two groups of mice. One group was active, and given an exercise wheel for 25 days, and the second group was sedentary, and was not provided the exercise wheel. After 25 days, they measured the mitochondrial proteins in skeletal muscle from both groups to see how the supercomplexes had changed over time.  When scientists typically analyze how supercomplexes form, they use antibodies to measure one or two proteins per electron transport chain complex. But as there can be up to 44 proteins in a complex, this method is both time consuming and provides limited information about what happens to the remainder of the proteins in each complex.  As a result, there is a lack of detailed knowledge in the field. Proteomics helps supercomplexes give up their secrets To generate much more detailed data, the team applied a proteomic technology called mass spectrometry to measure the mitochondrial proteins. By applying proteomics instead of antibodies, the scientists were able to measure nearly all of the proteins in each complex. This provided unprecedented detail of mitochondrial supercomplexes in skeletal muscle and how exercise training influences their formation. Their approach demonstrated that not all of the proteins in each complex or a supercomplex respond to exercise in the same manner.  "Mitochondrial protein content is known to increase with exercise, thus understanding how these proteins assemble into supercomplexes is crucial to decipher how they work. Our research represents a valuable and precious resource for the scientific community, especially for those studying how the mitochondrial proteins organize to be better at what they do best: produce energy under demand,", explains Postdoc Alba Gonzalez-Franquesa. The interdisciplinary project was a collaboration between the Deshmukh, Treebak and Zierath Groups at CBMR, and the Mann Group at the Novo Nordisk Foundation Center for Protein Research.

Memory And The Dreaming Mind If you’ve ever stayed up too late studying for a test, you know that sleep impacts memory—you need that precious shut-eye in order to encode and recall all that information. But what is it about sleep that aids memory?  Researchers have pinpointed a specific stage of sleep, REM sleep, as an area of interest for studying memory consolidation. REM, or rapid eye movement sleep, is the same stage in which dreams occur. So researchers at Northwestern University devised a way to communicate with lucid dreamers—people who are aware of their dreams and can control what they do in them—as a way to study how memories get made. Science Friday producer Katie Feather talks with Ken Paller, professor of psychology at Northwestern University to discuss what lucid dream research has taught us about memory. Progress In Considering Sex As A Biological Variable Back in 2013, Charles Hoeffer from the University of Colorado Boulder was studying memory and learning in mice. He was looking at a specific protein in the brain called AKT1, which helps mice forget an old task and learn a new one. In humans, a mutation in that protein has been linked to disorders like schizophrenia, Alzheimer’s and depression.  But in a follow-up study, Hoeffer did something different. He included both male mice and female mice, and then tested them separately. As expected, he discovered that male mice had a much tougher time learning the task when AKT1 wasn’t working. But in female mice, he found the unexpected: It didn’t make any difference whether the protein was removed or not. In other words, the sex of the mouse became an important variable that affected the outcome of the research. Hoeffer’s study is one example of considering sex as a biological variable (SABV) in pre-clinical research. And in 2016, the National Institutes of Health’s Office of Research on Women’s Health made it an official policy for researchers applying for funding.  But that didn’t change things overnight. Five years later, the approach is still catching on in many areas of research. Chyren Hunter, from the Office of Research on Women’s Health, joins Ira to discuss the progress that’s been made, and what lies ahead for the effort to make pre-clinical research more inclusive. Further information on the NIH’s policy on sex as a biological variable is on its website. The Problem With ‘Parachute Science’ “Parachute science” is a term describing how researchers sometimes drop down from an ivory tower in the wealthy Western world into a foreign community for field work. They gather their data, and then zip off home without engaging with or acknowledging the contributions of the local researchers in that community. This week in the journal Current Biology, researchers tried to quantify just how widespread that tendency is in one area of study—coral reefs.Searching through fifty years of publications published on the topic of warm water coral reef biodiversity research, they found that in 22% of the studies on coral reef ecosystems in Australia, there were no Australian researchers included as authors on the publication. The effect was even more noticeable in lower-income countries, such as Indonesia and the Philippines—where 40% of the published studies on coral reefs included no local scientists.  Ira talks with two of the study’s authors, Paris Stefanoudis and Sheena Talma, about what they found, and how researchers can work to make science more inclusive. The Global COVID-19 Supply Problem  Of the more than 200 million COVID-19 vaccines that have made it to patients’ arms this winter, more than a quarter have gone to people in the United States—a country with 4 percent of the total world population. Just last week, UN Secretary-General Antonio Guterres said that 75% of the world’s vaccinations so far had been in just 10 countries—while 130 countries had not received a single dose.  Meanwhile, on Wednesday, the nation of Ghana was the first to receive vaccines—600,000 doses—shipped as part of COVAX, a multi-national program which aims to provide as many as two billion free vaccines to poor and middle-income countries by the end of the year. Ira talks to Yale global health expert Saad Omer about the international effort to move vaccines equitably around the world, and the remaining hurdles for poorer countries.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.14.340067v1?rss=1 Authors: Okerman, T., Jurgenson, T., Moore, M., Klein, A. H. Abstract: Background: Opioid management of chronic pain can cause opioid-induced analgesic tolerance and hyperalgesia, complicating clinical pain-management treatments. Research presented here sought to determine if opioid induced tolerance is linked to activity changes within the PI3K{gamma}-AKT-cGMP-JNK intracellular signaling pathway in spinal cord or peripheral nervous systems. Methods: Morphine or saline injections were given subcutaneously twice a day for five days (15 mg/kg) to male C57Bl6 mice. A separate cohort of mice received spinal nerve ligation (SNL) one week prior to the start of morphine tolerance. Afterwards, spinal cord, dorsal root ganglia, and sciatic nerves were isolated for quantifying total and phosphorylated- JNK levels, cGMP, and gene expression analysis. Results: Gene expression for the PI3K{gamma}-AKT-cGMP-JNK signaling pathway including, Akt1, Akt2, Akt3, Pik3cg, Pten, Jnk3, and nNos1 were decreased in the spinal cord with varied expression changes in the dorsal root ganglia and sciatic nerve of morphine tolerant and morphine tolerant mice after SNL. We observed significant increases in total and phosphorylated- JNK levels in the spinal cord, total JNK in dorsal root ganglia, and cGMP in the sciatic nerve of morphine tolerant mice with SNL. Pharmacological inhibition of PI3K, nNOS, or JNK, using thalidomide, quercetin, or SP600125, attenuated the development of morphine tolerance in mice with SNL as measured by thermal paw withdrawal. Conclusions: Overall, the PI3K/AKT intracellular signaling pathway is a potential target for reducing the development of morphine tolerance. Continued research into this pathway will contribute to the development of new analgesic drug therapies. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.25.313635v1?rss=1 Authors: Wani, A. H., Aiello, A. E., Kim, G. S., Xue, F., Martin, C. L., Ratanatharathorn, A., Qu, A., Koenen, K., Galea, S., Wildman, D. E., Uddin, M. Abstract: Background: A range of factors have been identified that contribute to greater incidence, severity, and prolonged course of post-traumatic stress disorder (PTSD), including: comorbid and/or prior psychopathology; social adversity such as low socioeconomic position, perceived discrimination, and isolation; and biological factors such as genomic variation at glucocorticoid receptor regulatory network (GRRN) genes. This complex etiology and clinical course make identification of people at higher risk of PTSD challenging. Here we leverage machine learning (ML) approaches to identify a core set of factors that may together predispose persons to PTSD. Methods: We used multiple ML approaches to assess the relationship among DNA methylation (DNAm) at GRRN genes, prior psychopathology, social adversity, and prospective risk for PTS severity (PTSS). Results: ML models predicted prospective risk of PTSS with high accuracy. The Gradient Boost approach was the top-performing model with mean absolute error of 0.135, mean square error of 0.047, root mean square error of 0.217, and R2 of 95.29%. Prior PTSS ranked highest in predicting the prospective risk of PTSS, accounting for >88% of the prediction. The top ranked GRRN CpG site was cg05616442, in AKT1, and the top ranked social adversity feature was loneliness. Conclusion: Multiple factors including prior PTSS, social adversity, and DNAm play a role in predicting prospective risk of PTSS. ML models identified factors accounting for increased PTSS risk with high accuracy, which may help to target risk factors that reduce the likelihood or course of PTSD, potentially pointing to approaches that can lead to early intervention. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.31.275909v1?rss=1 Authors: Lu, W.-C., Omari, R., Ray, H., Carpenter, R. L. Abstract: The heat stress response activates the transcription factor heat shock factor 1 (HSF1), which subsequently upregulates heat shock proteins to maintain the integrity of the proteome. HSF1 activity requires nuclear localization, trimerization, DNA binding, phosphorylation, and gene transactivation. Phosphorylation at S326 is an important regulator of HSF1 transcriptional activity. Phosphorylation at S326 is mediated by AKT1, mTOR, p38, and MEK1. mTOR, p38, and MEK1 all phosphorylated S326 but AKT1 was the more potent activator. Mass spectrometry showed that AKT1 phosphorylated HSF1 at T142, S230, and T527 in addition to S326 whereas the other kinases did not. Subsequent investigation revealed that phosphorylation at T142 is necessary for HSF1 trimerization and that S230, S326, and T527 are required for HSF1 gene transactivation and recruitment of TFIIB and CDK9. This study suggests that HSF1 activity is regulated by phosphorylation at specific residues that promote different stages of HSF1 activation. Furthermore, this is the first study to identify the functional role of these phosphorylation events. Copy rights belong to original authors. Visit the link for more info

"Man kan se med det samme på dig, at du aldrig har været oppe efter midnat" TAGTERASSEN Dramatiker: Xiao Jing(CHN) Oversættere: Jimbut Jun Feng, Gritt Uldall-Jessen Skuespillere: Hanin Georgis, Laura Skjoldborg Iscenesættelse: Xiao Jing(CHN), Niels Erling Lydscenografi og redigering: Rasmus Juncker Arrangør, producent og fundraising: Nydanskeren Jimbuts Kulturforening TAGTERASSEN er et kunstnerisk samarbejde mellem Nydanskeren Jimbuts Kulturforening og AKT1. TAGTERASSEN er støttet af Statens Kunstfond, Frederiksberg Kommune og S. C. Van-fonden.

Sidste podcast i 2017! Vi besøger balletmester på Det Kongelige Teter, Nikolaj Hübbe, i hans kontor på Gamle Scene. Vi er dog også på besøg i Skuespilhuset ved kunsterkollektivet Sort Samvittighed under prøverne på deres akutelle forestilling 'TOVETOVETOVE'. Derudover snakker vi om AKT1 Radiodrama, 'Min Mor Siger' og om alle de mange forestillinger, vi glæder os til i det nye år. GOD JUL OG GODT NYTÅR. VI LYTTES VED I 2018.

Fra digter til dramatiker: Kunstnersamtale mellem Tine Høeg, Nanna Goul, Victor Boy Lindholm og Niels Erling, modereret af Klaus Rothstein Hvad sker der, når man beder en digter skrive dramatik? AKT1 har gjort det til sin mission at invitere nye stemmer ind i samtidsdramatikken med sit særlige debutformat for radiodramatikere, som forløses i et levende møde med publikum, der er med til optagelsen. Hvorfor skal digtere og forfattere skrive (radio)dramatik? Hvad får de selv ud af eksperimentet? Og hvad får dramatikken tilbage ved at inddrage skribenter, der arbejder i andre kunstneriske tekstformater? Vi varmer op til hørespilsoptagelserne med en kunstnersamtale modereret af litteraturkritiker og teateranmelder Klaus Rothstein om ny (radio)dramatik, litteratur og scenekunst med de aktuelle AKT1-debutanter digter Tine Høeg og forfatter Nanna Goul, digter og tidligere AKT1-debutant Victor Boy Lindholm samt instruktør og AKT1s kunstneriske leder Niels Erling.

ET LØV FALDER NED Live på KB18, oktober 2016 Manuskript: Sofie Diemer Instruktion: Sargun Oshana Medvirkende: Laura Skjoldborg Lydscenografi: Rasmus Juncker Teknik: Morten Frank

DU HAR VIRKELIG ÆNDRET DIG MEGET Live på CPH Stage NatCabaret, juni 2016 Manuskript: Jonas Wilmann Instruktion: Nicolai Nyholm Medvirkende: Youssef Hvidtfeldt, Jesper Groth og Christian Gade Bjerrum Lydscenografi: The Bowdashes Teknik: Morten Frank

AFTENRØDE Live på CPH Stage NatCabaret, juni 2016 Manuskript: Lars Kramhøft Instruktion: Daniel Kragh-Jacobsen Medvirkende: Ina-Miriam Rosenbaum, Sune Kofoed og Janus Elsig Lydscenografi: Marc Breidfjord Teknik: Morten Frank

Hör musikalisk kreativitet ihop med förmåga till unika associationer, att vara excentrisk, too much, heldeppig, gränsöverskridande eller hyperaktiv? Kort sagt - allt annat än mainstream. Del 1 av 4. Vad har Britney Spears, Robert Schumann och Amy Winehouse gemensamt? Eller Gioacchino Rossini, som skrev 40 operor på 20 år, och singersongwritern Jeff Buckley? Beethoven och Nina Simone? Tom Waits och Mozart? Hör galenskap och genialitet ihop? 2012 tilldelades Benjamin Staern Sveriges största tonsättarpris, Christ Johnsonpriset, på 180 000 kronor, för sin klarinettkonsert Worried Souls, Oroade själar, med solisten Karin Dornbusch och Norrköpings Symfoniorkester under ledning av Stefan Solyom. Svenska musikaliska Akademin gav motiveringen: "Med häpnadsväckande förmåga hanterar Benjamin Staern stora musikaliska former på ett originellt och personligt sätt, i ett verk präglat av rikt varierad orkestrering och bländande virtuositet i solostämman." Benjamin Staern har flera utvidgade sinnen; dels absolut gehör och dessutom synestesi. Benjamin hör färger i toner och ser toner i färger. Detta förstod han först själv när han vid Universitet i Lund började läsa om tonsättaren Arnold Schönbergs samarbete med bildkonstnären Vassily Kandinsky. Även tonsättarna Olivier Messiaen och Nikolaj Rimskij-Korsakov var synestetiker. När Benjamin Staern ser en speciell färg hör han en bestämd ton. Och när han hör en ton ser han en färg. Samma ton högre upp i oktaven har en ljusare nyans än den lägre tonen. Färgen svart är tystnad. Tonen C är vit. G-klaven ser han i gult, altklaven i rött, tenorklaven i brunt, basklaven i blå färg, blåsinstrumenten i grön färg och slagverken har ett brus av grå nyanser eller tonkluster, eftersom de ofta inte har någon fixerad tonhöjd. Experimentstycket för brassensemble Colour Wandering är en färgvandring där Benjamin Staern lät färgerna styra det musikaliska uttrycket. Här bygger han upp samma melodi i olika hastigheter samtidigt. Då uppstår det bland annat kvartstoner, vilket han sjunger för oss i programmet. Han har ju absolut gehör. Men ibland blir det kaos i Benjamin Staerns hjärna när han till exempel under en konsert bombarderas av musikens alla färger eller när han ständigt översköljs av toner när han ser färger. Även det absoluta gehöret kan ge upphov till frustrationer. Men när han komponerar så överröstar hans egna musikaliska infall alla de andra tonerna och färgerna i huvudet! När jag var sju år hörde jag en repetition av Verdis opera La Traviata och huvudrollen sjöng en kvartston fel. Då mådde jag illa, på samma sätt som när jag hör mikrotoner. Då kan jag se fler färger än vanligt. Det är som att se bensin på trottoaren eller att se flera strimmor framför mig som blir missfärgade, liksom fraktalmålningar, Mandelbrot. Toner och färger krockar med varandra och en märklig mosaik uppstår. Det är helt surrealistiskt, skrattar Benjamin Staern, som föddes med Kraniosynostos, vilket betyder att fontanellerna hos honom som litet barn slöt sig alltför tidigt. Det här är något som sker för ett barn på 2 000 födda. Han opererades som bebis och var helt stum mellan 2 år och 6 år. Benjamin Staern diagnostiserades då med en speciell form av autism. Det är samma diagnos som Gustav III hade, berättar Benjamin. Även Stanley Kubrick och Glenn Gould var förmodligen autister. Jag grät när jag såg filmen Rain Man med Dustin Hoffman, eftersom jag kände igen mig. Musiken har hjälpt mig i livet. Jag har med åren vant mig vid mina utvidgade sinnen och upplever dem nu som fantastiska. Jag är stolt över den jag är, säger Benjamin Staern och skrattar sitt härliga skratt.   Benjamin är son till den legendariske dirigenten Gunnar Staern, som ledde orkestern som senare blev Kungliga filharmonikerna. Han dirigerade även Gävle Symfoniorkester, Stora Teaterns Orkester i Göteborg och Malmö Operaorkester. Min far hade 5 000 partitur från ett helt yrkesliv. Jag blev mycket intresserad av den grafiska bilden i komplexa partitur, t ex hos Krzysztof Penderecki och Witold Lutosawski. Redan som sexåring började jag kopiera noter från de partitur som min pappa använde i sitt arbete, berättar Benjamin. Gunnar Staern avled 2011. Mamma Harriet Staern har varit körsångerska och kostymansvarig på Malmöoperan och är nu påklädare på samma opera där även Benjamin arbetar som notbibliotikarie. Han sorterar noter och stämmor. Det är en vilopunkt i skapandet, säger han själv. Benjamins mamma har varit och är fortfarande ett stort stöd för Benjamin. Hon tog hand om honom medan fadern var ute och jobbade på fältet, som Benjamin Staern säger. Tidigare i mitt liv hade jag problem med grovmotoriken. Jag var ofta ute och spelade cello och piano med flera ungdomsorkestrar och då var mamma ett ovärderligt stöd för mig. Nuförtiden går mamma och jag tillsammans på uruppföranden av både konserter och operor. Benjamin Staern slog igenom år 2000 med det symfoniska verket The Threat of War, Krigshot, som fick stort internationellt gensvar. Hans stycken har framförts på flera scener i Sverige, i Tyskland, i Tokyo, på Island och i Skottland. Numera får Benjamin Staern beställningar från orkestrar, ensembler och musiker runt om i Europa. Under tre år var han Composer-in-residence hos New European Ensemble i Holland. Han komponerade ett helaftonsstycke som uruppfördes av denna ensemble 2014, då Umeå var europeisk kulturhuvudstad. Musiklista:Fire And ImprovisationEmil Jonason,Emil JonasonREHABAmy Winehouse,Mbuyamba, NaAmy WinehouseAmy WinehouseISLAND RECORDS00407, 171 782 3Cp SkräckMbuyambaMad OddsFire And ImprovisationEmil Jonason,Emil JonasonWorried SoulsBenjamin Staern,Karin DornbuscNorrkopings SymfoniorkesterStefanSolyom, DirIL BARBIERE DISIVIGLIA: NR 7 (5), AKT1, "UNA VOCE POCOFA"Gioacchino Rossini,Cesare SterbiniMalena Ernman/ AlbertoHold-Garrido/ Stockholm SinfoniettaROXY RECORDINGS29117, 1019892YELLOW SKIESBenjamin Staern,Anna Svensdotter/Benjamin StaernSFZ RECORDS 23788, SFZ 1016 Yellow SkiesBenjamin Staern,Anna Svensdotter/Benjamin StaernSFZ RECORDS 23788, SFZ 1016Colour WanderingBenjamin Staern,Musikhögskolans I Malmö BrassensembleHåkan Hardenberger, DirColour WanderingBenjamin Staern,Musikhögskolans I Malmö BrassensembleHåkan Hardenberger, Dir Il Barbiere Di Siviglia: Nr7 (5), Akt 1, "Una Voce Poco Fa"Gioacchino Rossini,Cesare SterbiniMalena Ernman/ Alberto Hold Garrido/ Stockholm SinfoniettaRoxy Recordings 29117, 1019892Colour WanderingBenjamin Staern,Musikhögskolans I Malmö BrassensembleHåkan Hardenberger, DirJubilateBenjamin Stearn,BBC Scottish Symphony OrchestraFire And ImprovisationEmil JonasonEmil JonasonThreat Of WarBenjamin Stearn,Gävle SynfoniorkesterMats Rondin, DirTranströmersångerBenjamin Stearn,New European EnsembleCarina Vinke Christian Karlsen, DirNATTENS DJUPA VIOLONCELLBenjamin Staern,Karin BoyeAnna Larsson/ JanRisberg/ SonanzaPHONO SUECIA 00408, PSCD 180

FEBERDRØMME Live på DieselHouse, april 2016 Manuskript: Runi Weihe Instruktion: Kasper Sejersen Medvirkende: Neel Rønholt, Nicklas Søderberg Lundstrøm og Esben Dalgaard Andersen Lydscenografi: Sanne Dasseville Teknik: Morten Frank

VI ER JO IKKE IDIOTER Live på DieselHouse, april 2016 Præsenteres i samarbejde med Dagbladet Information Manuskript: Kronikker fra Dagbladet Information af Bent Vinn Hansen og Mikka Tecza, bearbejdet af Thea Kulavig Instruktion: Sigrid Johannessen Medvirkende: Signe A. Mannov, Ulrik Waarli Grimstad og Mikkel Hansen Lydscenografi: Mads Fisker og Daniel Ashok Skjødt Teknik: Morten Frank

Da vi skiftede til vores nye podcastfeed, kunne vi desværre ikke rykke alle vores gamle afsnit med over. Det nye feed startede derfor ved podcast 28. Vi synes dog ikke, I skal snydes for de gamle, hvorfor vi nu udgiver dem løbende i en lettere redigeret udgave. I dette arkivprogram kan du høre et interview med skuespilchef Morten Kirkskov, samt høre et indslag om radiodramapodcasten AKT1. 

PUSTERUM IN ABSURDUM Live på DieselHouse, april 2016 Manuskript: Felicia Ohly (SE) Instruktion: Camille Sieling Langdal Medvirkende: Emma Sehedsted Høeg, Magnus Bruun og Stina Mølgaard Oversættelse: Niels Erling Teknik: Morten Frank

Live på Transistor Sound - Festival for hørespil og radioteater i Malmö, april 2016 Manuskript: Martin Bengtsson (SE) Instruktion: Stefan Stanisic (SE) Medvirkende: Rosa Sand Michelsen Lydscenograf: Marc Breidfjord Oversættelse: Anna Schulin-Zeuthen Teknik: Morten Frank

Live på Transistor Sound - Festival for hørespil og radioteater i Malmö, april 2016 Manuskript: Robin N Spegel (SE) Instruktion: Carina Ehrenholm (SE) Medvirkende: Durita Dahl Andreassen, Linn Mildehav (SE) og Mette K. Madsen Lydscenograf: Frederik Bækgaard Ludwigs og Lukas Wendt Oversættelse: Niels Erling Teknik: Morten Frank

DET EXCEPTIONELLE ØJEBLIK HVOR BARBIE FIK CHANCEN FOR AT FLYGTE VÆK MED KEN I DEN RØDE SPORTSVOGN MEN GAV CHANCEN TIL SKIPPER Live på Transistor Sound - Festival for hørespil og radioteater i Malmö, april 2016 Manuskript: Anja Grim (SE) Instruktion: Jörgen Dahlqvist (SE) Medvirkende: Anne Plauborg og Sofie Torp Lydscenograf: Jörgen Dahlqvist (SE) Oversættelse: Niels Erling Teknik: Morten Frank

ET NO STRESS-ALBUM FOR PIKKEN Live i Dome of Visions, januar 2016 Præsenteres i samarbejde med AF·ART Magazine Tekst: Artiklen "Bag om værket Sheehan Casting Couch" af Nils Bloch fra AF·ART Magazine Bearbejdelse: Marie Bjørn Instruktion: Emil Rostrup Medvirkende: Henriette Katrine Lund, Anders Kristian Aamodt og Simon Bennebjerg Teknik: Morten Frank

FØDT I 1991 Live på Den Frie, januar 2016 Præsenteres i samarbejde med Dagbladet Information Tekst: Kronikker fra Dagbladet Information af Anton Sørensen, Birgitte Antonius, Max Martinussen og Tenna Ida Udesen samt et udvalg af Inger Christensens digte fra samlingen 'Handlingen' Bearbejdelse: Thea Kulavig og Stefan Stanisic Instruktion: Stefan Stanisic Medvirkende: Maria Stenz, Pernille Schrøder og Jannie Faurschou Teknik: Morten Frank

PÅ SPORET AF ALLAN Live på Den Frie, januar 2016 Manuskript: Mikkel Trier Rygaard Instruktion: Nicolai Nyholm Medvirkende: Alexander Clement, Josephine Nørring og Ulver Skuli Abildgaard Lydscenograf: Sanne Dasseville Teknik: Morten Frank

VERDENSBORGER NR. 1 Live på Den Frie, januar 2016 Manuskript: Victor Boy Lindholm Instruktion: Johan Sarauw Medvirkende: Josephine Park og Sicilia Gadborg Høegh Lydscenograf: Theis Vesterløkke Teknik: Morten Frank

ATHEN Live på Den Frie, januar 2016 Manuskript: Esben Weile Kjær Instruktion: Sargun Oshana Medvirkende: Jens Sætter-Lassen og Morten Hee Andersen Lydscenograf: Lotte Rose Kjær Skau Teknik: Morten Frank

FREELANCE Live på Byens Lys, oktober 2015 Manuskript: Anders Haahr Rasmussen og Kian Fonoudi Instruktion: Emil Rostrup Medvirkende: Sebastian Jessen, Sidsel Siem Koch, Jacob Teglgaard og Robert Reinhold Lydscenograf: Theis Vesterløkke Teknik: Morten Frank

AT SULTE SIG ER EGOISME Live på Byens Lys, oktober 2015 Manuskript: Manda Stenström Instruktion: Kasper Sejersen Medvirkende: Marie-Lydie Nokouda Lydscenograf: Sanne Dasseville Teknik: Morten Frank

JEG HAR IKKE TALENT FOR KÆRLIGHED Live på Byens Lys, oktober 2015 Præsenteres i samarbejde med Dagbladet Information Tekst: Kronikker fra Dagbladet Information af Ulrik Frost, Iben Thranholm og Julie Top-Nørgaard Bearbejdelse: Marie Bjørn og Thea Kulavig Instruktion: Carina Ehrenholm Medvirkende: Jens Alexander Kepny Kristensen, Anders Kristian Aamodt og Sigurd Holmen Le Dous Teknik: Morten Frank

EFTER VOLDEN Live på Byens Lys, oktober 2015 Manuskript: Johannes Lilleøre Instruktion: Niels Erling Medvirkende: Kristian Halken, Johanne Louise Schmidt og Nanna Skaarup Voss Lydscenograf: Theis Vesterløkke Teknik: Morten Frank

LIGEVÆGTIG AKT1 feat. Zulu Comedy Festival - optaget live i Det Røde Rum i august 2015 Manuskript: Søren Dürr Instruktion: Liv Helm Medvirkende: Nanna Cecilie Bang, Jesper Groth og Jens Andersen Teknik: Morten Frank

FAIRTRADE AKT1 feat. Zulu Comedy Festival - optaget live i Det Røde Rum i august 2015 Manuskript: Zainab Ahmed Instruktion: Claudio Morales Medvirkende: Josephine Raahauge, Mohamed Ali Osman, Zaineb Ahmed og Youssef Hvidtfeldt Teknik: Morten Frank

BANKRØVERNE AKT1 feat. Zulu Comedy Festival - optaget live i Det Røde Rum i august 2015 Manuskript: Brian Lykke Instruktion: Nicolai Nyholm Medvirkende: Adam Ild Rohweder, Niklas Bentzen og Mads M. Nielsen Teknik: Morten Frank

FLYGTNING AKT1 feat. Zulu Comedy Festival - optaget live i Det Røde Rum i august 2015 Manuskript: Mark Le Fevre og Mikkel Rask Instruktion: Line Paulsen Medvirkende: Tilde Maja Frederiksen, Benjamin Boe Rasmussen og Morten Hembo Teknik: Morten Frank

VELKOMMEN TIL DANMARK Optaget live på Husets Teater som en del af FLYD - Festival for Lyddramatik 2015 Tekst: Kronikmateriale fra Dagbladet Information Bearbejdelse: Anders Djurslev og Marie Bjørn Instruktion: Kasper Sejersen Medvirkende: Ina-Miriam Rosenbaum og Anders Heinrichsen Teknik: Anders Munch Amdisen

DE NATTEGALE I OMER Optaget live på Husets Teater som en del af FLYD - Festival for Lyddramatik 2015 Manuskript: Nanna Tychsen Instruktion: Emil Rostrup Medvirkende: Alexander Clement og Hans Henrik Clemensen Musik: Louis Petri Teknik: Anders Munch Amdisen

PIANO Optaget live i Nikolaj Kunsthal, maj 2015 Manuskript & udførelse: Betina Birkjær Øvrige medvirkende: Nicolai Jandorf & Niels Erling Lyddesign: Inuk Thomsen Spilledåselyd: Stephan Laidet Klaverstykke: Nocturnes af Chopin fremført af Maurizio Pollini Teknik og redigering: Morten Frank og Julie Pedersen

PARMIDDAG Optaget live i Nikolaj Kunsthal, maj 2015 Manuskript: Irmelin Prehn Instruktion: Nicolai Nyholm Medvirkende: Sofie Ancher Vea, Nicolai Jandorf, Anne Vester Høyer, Christian Gade Bjerrum og Stefanía Ómarsdóttir Lydredigering: Morten Frank og Julie Pedersen

I FORHOLD TIL ANETTE Optaget live i Nikolaj Kunsthal, maj 2015 Manuskript: Simon Holm Pedersen Instruktion: Stefan Stanisic Medvirkende: Sara Line Møller Olsen, Morten Holst og Signe Kærup Hjort Lydredigering: Morten Frank og Julie Pedersen

JEG RÅBER HERNEDE FRA BUNDEN Præsenteres i samarbejde med Dagbladet Information Optaget live i Nikolaj Kunsthal, maj 2015 Tekst: Kronikmateriale fra Dagbladet Information (Sarah Elizabeth Daley: 'Kære Inger Støjberg, Jeg råber til dig hernede fra bunden' og Thomas Steen Parum: 'Kontanthjælpsmodtager: Jeg nægter at skamme mig') Bearbejdelse: Anders Djurslev og Liv Helm Instruktion: Line Paulsen Medvirkende: Joachim Fjelstrup, Andreas Berg Nielsen og Amalie Lindegård Lydredigering: Morten Frank og Julie Pedersen

UDE I FORSTADEN Optaget live i Dome of Visions, februar 2015 Manuskript: Daniel Vatsvåg Instruktion: Nicolai Nyholm Medvirkende: Claes Bang, Alexander Clement og Christine Sønderris Lydredigering: Anders Amdisen og Morten Frank

UDE I FORSTADEN Præsenteres i samarbejde med Dagbladet Information Optaget live i Dome of Visions, februar 2015 Efter en kronik skrevet af Mette R. Jakobsen bragt i Information 12. juli 2010 Bearbejdet og instrueret af Liv Helm Medvirkende: Mette K. Madsen og Claus Flygare Lydredigering: Anders Amdisen og Morten Frank

CORNWALL Optaget live i Dome of Visions, februar 2015 Manuskript: Lars Bo Nørgaard Instruktion: Stefan Stanisic Medvirkende: Niclas Kølpin og Zaki Nobel Mehabil Lydredigering: Anders Amdisen og Morten Frank

DRØMMEDØD Præsenteres i samarbejde med Dagbladet Information Optaget live i vinterhaven på Krausesvej 3, november 2014 Efter en kronik skrevet af Lise Uhrup og bragt i Information 23. oktober 2014 Bearbejdet og instrueret af Liv Helm Medvirkende: skuespillerinde Lone Hertz og sangerinde Anna Mose Lydredigering: Jonas Schou Hansen og Morten Frank

HUSK BLOMSTER Optaget live i vinterhaven på Krausesvej 3, november 2014 Manuskript: Martin Snoer Raaschou Instruktion: Stefan Stanisic Medvirkende: Nanna Bøttcher, Youssef Hvidtfeldt og Ulver Skuli Abildgaard Lydredigering: Jonas Schou Hansen og Morten Frank

LILLE DUKKE Optaget live i vinterhaven på Krausesvej 3, november 2014 Manuskript: Marie Markvardt Andersen Instruktion: Claudio Morales Medvirkende: Anne Reumert, Mikkel Hansen og Marianne Mortensen Lydredigering: Jonas Schou Hansen og Morten Frank

NAUSICA NAUSICA Optaget foran livepublikum i vinterhaven på Krausesvej 3, november 2014 Manuskript: Mikkel Rosenberg Instruktion: Henrik Grimbäck Medvirkende: Christine Albeck Børge, Sara Ullner og Lise Lauenblad Lydredigering: Jonas Schou Hansen og Morten Frank

FRISK LUFT, BESØG OG FRI TANDPLEJE Optaget foran livepublikum på FLYD - Festival for Lyddramatik i august 2014 Manuskript: Nanna Cecilie Bang Instruktion: Claudio Morales Medvirkende: Marie Mondrup Lydredigering: Morten Frank og Inuk Thomsen

JEG SVÆRGER Optaget foran livepublikum på Vela Bar i København i maj 2014 Manuskript: Amanda Ginman Instruktion: Sabrina Ruiz Medvirkende: Nanna Schaumburg-Müller og Amira Jasmina Jensen Lydredigering: Morten Frank

EKSIL Optaget foran livepublikum på Vela Bar i København i maj 2014 Manuskript: Morten Ettrup Instruktion: Emil Rostrup Medvirkende: Christian Bergman og Thomas Ernst Lydredigering: Morten Frank

AT SE RØDT Optaget foran livepublikum på Vela Bar i København i maj 2014 Manuskript: Camille Sieling Langdal Instruktion: Martin Nyborg Medvirkende: Marie Knudsen Fogh og Preben Kristensen Lydredigering: Morten Frank

LIGEGYLDIGT Manuskript: Emma Bexell (SE) Instruktion: Henrik Grimbäck (SE/DK) Medvirkende: Josephine Raahauge og Marie Mondrup Lydredigering: Sofie Vadstrup Harder

FRISK LUFT, BESØG OG FRI TANDPLEJE Manuskript: Nanna Cecilie Bang Instruktion: Claudio Morales Medvirkende: Kitt Maiken Mortensen Lydredigering: Niels Porsborg

I DEN MØRKE MØRKE MØRKE SKOV Manuskript: Miriam Kathrine Valentin Boolsen Instruktion: Nicolai Nyholm Medvirkende: Nanna Cecilie Bang, Kit Eichler og Anders Mossling Lydredigering: Niels Porsborg

IKKE ALLE DER GÅR MED RØDE SOKKER Manuskript: Thomas Michaelsen Brøchner Instruktion: Anna Balslev Medvirkende: Penille Albæk Andersen, Kenneth M. Christensen, Jonas Kriegbaum og Luise Skov Lydredigering: Sofie Vadstrup Harder

LE BANQUET FINAL Manuskript: Magnus Iuel Berg Instruktion: Sargun Oshana Medvirkende: Meike Bahnsen, Peter Flyvholm og Sabrina Ruiz Lydredigering: Niels Porsborg

POTENS Manuskript: Marie Bjørn Instruktion: Henrik Grimbäck (SE) Medvirkende: Claus Flygare, Emil Gohr, Morten Klode og Amanda Bjerre-Petersen Lydredigering: Sofie Vadstrup Harder

SIMON Manuskript: Rasmus Elvers Instruktion: Liv Helm Medvirkende: Tina Gylling Mortensen, Johannes Nymark og Niels Erling Lydredigering: Niels Porsborg

HESTENE Manuskript: Kristina Pfeil Nielsen Bearbejdelse og Iscenesættelse: Jeremy M. Thomas-Poulsen Medvirkende: Helle Rossing, Laura Kvist, Claudio Morales og Anders Heinrichsen

UNIVERSETS LOVE Manuskript: Anna Panduro Bearbejdelse og iscenesættelse: Camille Sieling Langdal Skuespillere: Sofia Nolsøe og Anne Sofie Wanstrup Lydredigering: Niels Porsborg

UNDER TEKST Manuskript: Kristofer Grønskag (NO) Medvirkende: Marie Tourell Søderberg og Søren Hauch-Fausbøll Instruktion: Claudio Morales

LANGT OVER GRÆNSEN Manuskript: Amalie Munkgaard Olesen Bearbejdelse og iscenesættelse: Mette Ovesen Skuespillere: Lene Poulsen og Peter Hald Lydredigering: Kristina Pfeil

DET STORE BILLEDE Manuskript: Thea Kulavig Bearbejdelse og iscenesættelse: Nicolai Nyholm Skuespillere: Niels Erling og Nanna Voss Lydredigering: Kristina Pfeil

EN PILOT Manuskript: Rasmus Rhode Bearbejdelse og Iscenesættelse: Magnus Iuel Berg Skuespillere: Morten Vejbæk Klode, Maria La Cour og Jan Hertz Teknik: Sofie Vadstrup Harder

Just some time with Jesus worshiping positive talk and music from Jonathan Steingard's solo EPs http://jonathansteingard.blogspot.com/

Thu, 17 Apr 2008 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/8459/ https://edoc.ub.uni-muenchen.de/8459/1/Horvath_Christina.pdf Horvath, Christina

Hintergrund und Fragestellung Eines der schwerwiegenden Probleme der interventionellen Kardiologie stellte bislang die koronare Restenose im Stent dar. Erst durch die Einführung eines Rapamycin- freisetzenden-Stents konnte die Restenoserate erheblich gesenkt werden. Trotz dieses therapeutischen Erfolges sind die transkriptionellen pathophysiologischen Mechanismen der Neointimahyperplasie, die zu über 90% für den Lumenverlust nach koronarer Stentimplantation verantwortlich ist, sowie deren Beeinflussung durch Rapamycin nur teilweise verstanden. Methodik Die vorliegende Arbeit untersuchte deshalb in einem humanen Organkulturmodell auf genregulatorischer Ebene die molekularen Mechanismen, die der Neointimaformation im Menschen zu Grunde liegen, sowie die Beeinflussung dieser Mechanismen durch eine Behandlung mit Rapamycin. Ergebnisse Es konnte gezeigt werden, dass (1) die Veränderungen in der Genexpression einem zeitlichen Muster folgen mit maximalen Veränderungen 21 Tage nach Ballondilatation; (2) die inflammatorische Komponente zu den frühen Zeitpunkten eine wichtigere Rolle spielt während Proliferation und Apoptose die späteren Veränderungen in der Genexpression dominieren; (3) die Ballonangioplastie ein Genexpressionsprofil induziert, welches die Rekrutierung und Aktivierung sowohl inflammatorischer als auch hämatopoetischer Vorläuferzellen erleichtert; (4) Rapamycin die Induktion eines solchen pro-adhäsiven, proinflammatorischen Genexpressionsmusters als auch die Induktion von HPC-stimulierenden Genen verhindert. Diskussion Eine zeitlich gestaffelte Genexpressionsanalyse menschlicher Arterien nach Ballonangioplastie ist bisher nicht veröffentlicht worden. In dieser Arbeit zeigte sich, dass die Veränderungen in der Genexpression einem zeitlichen Muster folgen mit einer maximalen Alteration nach 21 Tagen und nur wenigen ausschließlich nach 56 Tagen regulierten Genen. Somit lässt sich schlussfolgern, dass eine spätere Restenose die Folge einer frühen, gestörten Wundheilung ist. Diese Auffassung wird durch die beeindruckende Verminderung der In-Stent-Restenose durch Rapamycin-freisetzende Stents unterstützt, da diese Stents etwa 80% der totalen Medikamentendosis innerhalb der ersten 30 Tage freisetzen. Während die Proliferation bekanntermassen eine wichtige Rolle für die Neointimaformation spielt, wurde die Bedeutung inflammatorischer Prozesse, welche zur Rekrutierung von Leukozyten und hämatopoetischen Vorläuferzellen führen, erst später vermehrt beschrieben. Die koordinierte Induktion eines in dieser Arbeit nachgewiesenen proinflammatorischen Genexpressionsmusters stellt eine beeindruckende Rationale für eine umfangreiche Rekrutierung von Leukozyten nach Ballondilatation dar. Zytokine wie IL-8, EMAP-II, NAP-2 oder GCP-2 waren nach Angioplastie vermehrt exprimiert und verstärken die Migration von Granulozyten. Die mechanisch induzierte Aktivierung dieses Genexpressionsmusters begünstigt somit die Leukozytenrekrutierung und dadurch auch die Restenose, da die Dichte inflammatorischer Zellen in der Neointima mit dem Ausmass der Restenose korreliert. Als weiterer Mechanismus der Neointimaformation wurde kürzlich die Rekrutierung hämatopoetischer Vorläuferzellen im Tiermodell nachgewiesen. Es war jedoch bisher nicht bekannt, ob sich diese Beobachtungen auf den Menschen übertragen lassen. Im Organkulturmodell zeigte sich nach Angioplastie die vermehrte Expression von einigen mit hämatopoetischen Vorläuferzellen assoziierten Genen. Dies weist daraufhin, dass diese Mechanismen auch im Menschen eine Rolle spielen. Im zweiten Teil dieser Arbeit wurde der Einfluss des Makrolidantibiotikums Rapamycin auf die transkriptionellen Mechanismen nach Ballonangioplastie untersucht. Zunächst spiegelten sich die bekannten antiproliferativen Effekte von Rapamycin in einer deutlich verminderten Expression von wachstumsassoziierten Genen wie verschiedenen Transkriptionsfaktoren und Kinasen wie JAK1 oder AKT1 wieder. Darüberhinaus führte die Rapamycinbehandlung zu einer koordinierten Hemmung der CXC Chemokine 6-8 (GCP-2, β- Thromboglobulin, IL-8) und von EMAP-II, welche alle eine wichtige Rolle in der Adhäsion, der Migration und der Aktivierung von Neutrophilen und Monozyten spielen. Folglich könnte eine durch Rapamycin veminderte Rekrutierung und Aktivierung dieser Zellen ein wesentlicher Mechanismus in der Reduktion der Neointimaformation sein. Zusätzlich unterstützt diese Arbeit die Hypothese, dass Rapamycin auch direkte Effekte auf hämatopoetische Vorläuferzellen hat. Im Organkulturmodell führte eine Rapamycinbehandlung zur veminderten Expression verschiedener Gene wie des Oncostatin M Rezeptors beta und JAK1, welche das Wachstum immaturer, noch differenzierender Zellen in der Gefässwand fördern. Es lässt sich zusammenfassen, dass Rapamycin neben seiner anti-proliferativen Wirkung nach Ballonangioplastie tiefgreifende hemmende Effekte auf das pro-inflammatorische Genexpressionsmuster und auf Promotoren hämatopoetischer Vorläuferzellen verübt. Somit zeigt diese Arbeit erstmals eine Rationale auf, wie Rapamycin auch im Menschen die Rekrutierung hämatopoetischer Vorläuferzellen in die Gefässwand verhindern könnte. Dies vermag möglicherweise seine hohe Effektivität in der Reduzierung der Restenose erklären.