Podcasts about tie2

The angiopoietin/Tie2 pathway is an attractive therapeutic target for the management of retinal and choroidal vascular diseases, as it has been identified to play a role in vascular permeability and angiogenesis within the eye. Several therapies targeting this pathway have been investigated, and the FDA recently approved the first agent that inhibits both the angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF)-A pathways for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Dual inhibition of these 2 pathways has the potential to enhance visual acuity outcomes while lowering the treatment burden. In this podcast, Dr. Carl Regillo and Dr. Nancy Holekamp discuss the efficacy and safety of therapies targeting Ang-2 in DME.

The angiopoietin/Tie2 pathway is an attractive therapeutic target for the management of retinal and choroidal vascular diseases, as it has been identified to play a role in vascular permeability and angiogenesis within the eye. Several therapies targeting this pathway have been investigated, and the FDA recently approved the first agent that inhibits both the angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF)-A pathways for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Dual inhibition of these 2 pathways has the potential to enhance visual acuity outcomes while lowering the treatment burden. In this podcast, Dr. Carl Regillo and Dr. Arshad Khanani discuss the efficacy and safety of therapies targeting Ang-2 in nAMD.

The angiopoietin/Tie2 pathway is an attractive therapeutic target for the management of retinal and choroidal vascular diseases, as it has been identified to play a role in vascular permeability and angiogenesis within the eye. Several therapies targeting this pathway have been investigated, and the FDA recently approved the first agent that inhibits both the angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF)-A pathways for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Dual inhibition of these 2 pathways has the potential to enhance visual acuity outcomes while lowering the treatment burden. In this podcast, Dr. Carl Regillo and Dr. Judy Kim discuss the Tie2 pathway and its role in the pathophysiology of retinal vascular diseases.

Does the P-Shot work? Who won't the P-Shot work for? Will the P-Shot work for you? Stephanie Wolff and David Dumbroski from The Novus Center answer your P-Shot questions. You can learn more about The P-Shot on our website: https://www.thenovuscenter.com/treatments-los-angeles/sexual-performance/p-shot/ Studies on PRP for Erectile Dysfunction: [CLINICAL STUDY] Recent advances in the understanding and management of erectile dysfunction: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348436/ [CLINICAL STUDY] Safety and feasibility of platelet rich fibrin matrix injections for treatment of common urologic conditions: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754585/ [CLINICAL STUDY] Platelet rich plasma extract promotes angiogenesis through the angiopoietin1-Tie2 pathway: https://pubmed.ncbi.nlm.nih.gov/23660186/ [CLINICAL STUDY] The influence of platelet-derived products on angiogenesis and tissue repair: a concise update: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4611136/ FDA DISCLAIMER: THESE STATEMENTS HAVE NOT BEEN EVALUATED BY THE UNITED STATES FOOD AND DRUG ADMINISTRATION (FDA). EXOSOME THERAPY, STEM CELL THERAPY, SHOCKWAVE THERAPY, PRP THERAPY OR REGENERATIVE MEDICINE THERAPY IS NOT FDA APPROVED TO PREVENT, CURE OR TREAT DISEASES OR CONDITIONS. PLEASE VISIT THE FDA WEBSITE (WWW.FDA.GOV) FOR ADDITIONAL INFORMATION, INCLUDING CONSUMER ALERTS REGARDING EXOSOME THERAPY, STEM CELL THERAPY, SHOCKWAVE THERAPY, PRP THERAPY OR REGENERATIVE MEDICINE THERAPY. MEDICAL DISCLAIMER: These videos or any videos on "The Novus Center" YouTube channel does not provide medical advice. The information, including but not limited to, text, graphics, images and other material contained on this website are for informational purposes only. No material on this channel is intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified healthcare provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this channel.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.19.304188v1?rss=1 Authors: Zhao, Y. T., Fallas, J. A., Saini, S., Ueda, G., Somasundaram, L., Zhou, Z., Xavier, I., Ehnes, D., Xu, C., Carter, L., Wrenn, S., Mathieu, J., Sellers, D. L., Baker, D., Ruohola-Baker, H. Abstract: Angiopoietin 1 and 2 (Ang1 and Ang2) modulate angiogenesis and vascular homeostasis through engagement of their very similar F-domain modules with the Tie2 receptor tyrosine kinase on endothelial cells. Despite this similarity in the underlying receptor binding interaction, the two angiopoietins have opposite effects: Ang1 induces phosphorylation of protein kinase B (AKT), strengthens cell-cell junctions and enhances endothelial cell survival while Ang2 antagonizes these effects. To investigate the molecular basis for the opposing effects, we examined the protein kinase activation and morphological phenotypes produced by a series of computationally designed protein scaffolds presenting the Ang1 F-domain in a wide range of valencies and geometries. We find two broad phenotypic classes distinguished by the number of presented F-domains: scaffolds presenting 4 F-domains have Ang2 like activity, upregulating pFAK and pERK but not pAKT, and failing to induce cell migration and tube formation, while scaffolds presenting 6 or more F-domains have Ang1 like activity, upregulating pAKT and inducing migration and tube formation. The scaffolds with 8 or more F-domains display superagonist activity, producing stronger phenotypes at lower concentrations than Ang1. When examined in vivo, superagonist icosahedral self-assembling nanoparticles caused significant revascularization in hemorrhagic brains after a controlled cortical impact injury. Copy rights belong to original authors. Visit the link for more info

In this MedEdTalks micro-CE podcast, Rishi P. Singh, MD, and Arshad M. Khanani, MD, MA, discuss new findings about emerging therapies that target the angiopoietin/Tie2 pathway that may improve the treatment of neovascular retinal diseases. Transcript: https://bit.ly/38jWicU To obtain CME Credit, please go here: https://bit.ly/2nBqmhq 

  Even though we have been having a terrific summer, innovation doesn’t just stop when the sun is beckoning, and the cottage is calling our name. It persists through rain and shine, and never has that been truer. Keep listening to find out what’s new this week!  +++++  Vasomune Therapeutics, a Toronto-based spin-out from Sunnybrook Research Institute and MaRS Innovation, and AnGes, Inc., a Japan-based biotechnology company focused on developing biotherapeutics, sign an innovative multi-million-dollar global Co-Development Agreement for the development and commercialization of therapeutics treating diseases associated with blood vessel dysfunction and destabilization.  The collaboration will advance Vasomune’s peptide-based Tie2 receptor agonist program, initially for the treatment of critical care indications, including Acute Respiratory Distress Syndrome (ARDS), into clinical development with the expectation of initiating clinical trials in 2020. Acute Respiratory Distress Syndrome is a critical care indication with a significant unmet medical need as there are currently no approved therapeutics.   With such a foundational mechanism involved in multiple disease states, the parties have the option to co-develop the compounds for additional indications associated with vascular dysfunction and leakage. These indications include asthma, atopic dermatitis, glaucoma and vascular complications of diabetes.  Parimal Nathwani, president and CEO of Vasomune Therapeutics says, “Vasomune is enthusiastic to combine our technology, scientific and preclinical expertise with the significant development capabilities and track record of our colleagues at AnGes through this unique partnership structure to maximize the opportunity for a Tie2 receptor agonist to benefit patients. AnGes’ commitment to developing truly novel biotherapeutic medicines directly aligns with Vasomune’s objectives.”  Under the terms of the agreement, AnGes will provide Vasomune with multi-million-dollar co-development contributions including upfront and clinical milestone fees. The initial objective of the partnership is to achieve human proof of concept in Acute Respiratory Distress Syndrome, which alone is could potentially be a US$2.5 billion market opportunity worldwide.  Ei Yamada, president and CEO, AnGes, states, “We are truly impressed by the quality of the research derived from Sunnybrook Research Institute and the unique partnership with MaRS Innovation that has created and advanced Vasomune Therapeutics. This program represents a significant commitment by AnGes to advance and develop truly innovative biotherapeutics towards commercialization for the benefit of patients.”  The partnership provides the option for continued co-development through to commercialization and expansion to other indications. The parties will share equally in all expenses and all proceeds including milestone and royalty payments from any third-party licensing transaction. Development and commercialization of the program will be managed through joint committees organized by the two companies.  Rafi Hofstein, president and CEO of MaRS Innovation  says, “We are honoured to have AnGes validate the strength and translatability of Vasomune’s science led by Dr. Paul Van Slyke, chief scientific officer and co-inventor. This unique partnership has attracted foreign capital and expertise to allow Vasomune, a Canadian born company to grow and scale in Canada and maintain the legacy of the late Dr. Daniel Dumont.”  +++++  Even as brief as two weeks of inactivity as an aging adult might put you at risk of developing type 2 diabetes according to a study conducted at McMaster University.  Not only did an abrupt, brief period of inactivity hasten the onset of the disease and elevate blood sugar levels among pre-diabetic patients, but researchers reported that some study participants did not fully recover when they returned to normal activity for two weeks.  The findings are published online in The Journals of Gerontology.  Lead author of the study, Chris McGlory, a diabetes Canada research fellow in the Department of Kinesiology at McMaster University says, “We expected to find that the study participants would become diabetic, but we were surprised to see that they didn’t revert back to their healthier state when they returned to normal activity.”  Participants were asked to reduce their daily steps to no more than 1000 steps per day, the equivalent of being housebound due to factors such as illness. Their steps and activity were measured using pedometers and specialized activity monitors, while researchers tested their blood sugar levels and took blood samples during the two-week period.  The results imply that seniors who experience periods of physical inactivity from illness, hospitalization and bed rest are more likely to suffer detrimental consequences to their overall health.  Stuart Phillips, the professor in the Department of Kinesiology at McMaster who oversaw the research explains, “Treatment of type 2 diabetes is expensive and often complicated. If people are going to be off their feet for an extended period they need to work actively to recover their ability to handle blood sugar.”  According to the most recent statistics from the Centres for Disease Control and Prevention, more than 30 million Americans have diabetes and more than 84 million are prediabetic.  In Canada, Type 2 diabetes is one of the fastest growing diseases, with nearly 60,000 new cases reported each year, according to the Public Health Agency of Canada.  It is the sixth leading cause of death and the leading cause of adult blindness and adult amputation.  In order for pre-diabetic older adults to recover metabolic health and prevent further declines from periods of inactivity, strategies such as active rehabilitation, dietary changes and perhaps medication might be useful.  This research has shown that within days of the onset of inactivity, there are substantial reductions in skeletal muscle mass, strength and a rapid onset of insulin resistance, which is a common feature of type 2 diabetes.  +++++  The Canadian Institutes for Health Research awards the University of Saskatchewan over $2.4 million for indigenous health care, stroke recovery, and cancer research.  Karen Chad, the vice-president of research says, “This major health funding will accelerate research into cancer, stroke, and infectious diseases such as HIV, improving the lives of patients and their families. This funding success also underscores our commitment to community-based research and to incorporating Indigenous ways of knowing.”  Dr. Alexandra King, Cameco chair in Indigenous health, is leading the two projects with an Indigenous focus: studying the potential benefits of peer support for Indigenous women who have HIV or hepatitis C and examining how to improve health and wellness in older Indigenous women living with HIV.  Saskatchewan has the highest rate of HIV in Canada––2.3 times higher than the national diagnosis rate, according to the provincial government. HIV and hepatitis disproportionately affect Indigenous peoples and particularly, Indigenous women.  King will observe the role of a “peer navigator” to determine if the support they extend to indigenous women living with HIV and hepatitis helps them better connect and receive backing from the health care system. Peer navigators are individuals who have gained the wisdom of specific conditions through lived experience, and who receive further training and education on health and related issues.  King says, “Within most Indigenous communities, we put great value on wisdom gained through lived experience. Peer navigators relate to patients in ways that physicians and nurses or other health professionals can not. It just makes sense to have peers involved in health care.”  King’s other study will involve engaging older Indigenous women who are living with HIV to collaboratively create and implement a wellness pilot project based on their self-defined programming needs in five communities in Saskatchewan and British Columbia.  King goes on to say that “Indigenous health research long ago embraced many of the same principles that patient-oriented research now does, in that people with lived experience of a health condition are involved throughout. We’re incorporating culture and ceremony as part of the research process, so the research itself is healing for participants and for the researchers.”  Microbiology and immunology researcher Linda Chelico will lead an $822,000 project to examine the activity of a specific family of enzymes that protect the body against viruses. But if there are too many enzymes, it could lead to a mutation in healthy DNA cells potentially leading to cancer.  Chelico will determine in breast cancer cells whether the enzymes can be used to predict cancer outcomes, be targeted to block cancer starting or progressing, or be used to suppress cancer evolving.  Pharmacy and nutrition researcher Phyllis Paterson is using a rat model to examine how better, more protein-rich nutrition after a stroke can bolster recovery of the brain and leg muscles, in part of a combination of therapies.  Protein-deficient nutrition affects 20 to 35 per cent of patients one-week post-stroke, and up to half of all patients during rehabilitation are protein-deficient due to challenges such as physical and mental disability, and difficulty swallowing.  Overall, the CIHR grants will pay for 14 staff positions and funding of six graduate students and one post-doctoral fellow.  +++++  Antibe Therapeutics Incorporated., a company developing safer therapeutics for pain and inflammation, updates its clinical development activities for its lead drug, ATB-346.  ATB-346 is a hydrogen sulfide-releasing derivative of naproxen. Nonsteroidal Anti-inflammatory Drugs are the most commonly used therapy for osteoarthritis, rheumatoid arthritis, gout, and general pain reduction, but their use is associated with a high rate of gastrointestinal ulceration and bleeding. Patients with these conditions would benefit greatly from an effective, non-addictive, Gastrointestinal-sparing anti-inflammatory/analgesic agent such as ATB-346.  The Phase 2 dose-ranging, efficacy study remains on track to commence this quarter. Furthermore, Antibe has been pursuing additional development activities that are required for regulatory approval and of strategic value to future partners. The company recently completed a series of animal metabolism studies that have provided key insights on the pharmacokinetic profile of ATB-346. These insights can now be leveraged to better determine the doses and dosing regimens to be used in the upcoming Phase 2 study.  Dan Legault, Antibe’s CEO, says, “Based on the recently reported COX inhibition data and metabolism insights, we have augmented our Phase 2 dose-ranging, efficacy study for ATB-346 to include two protocols. The first protocol will expand upon the metabolism findings which should enable us to better select the optimal doses for the subsequent protocol. Although this modestly extends the timelines of the overall study, it provides a faster path to obtaining the comprehensive package of efficacy and metabolism data that is required for regulatory bodies such as the FDA and valued by global partners.”  The upcoming Phase 2 study will now include a metabolism protocol that will directly inform the dosing cohorts to be used in the subsequent dose-ranging, efficacy protocol. Therefore, the updated development plan will include two parts:  Part 1: Characterization of Metabolites. The primary objective of the metabolism study is to determine the principle metabolites of ATB-346 in humans and characterize their activity and pharmacokinetic profile. The study will be conducted in approximately 25 healthy volunteers and is anticipated to commence this quarter and should take 8-10 weeks to complete.  Part 2: Validation of Effectiveness. The dose-ranging, efficacy study will be conducted in approximately 200 osteoarthritis patients. The primary objective of the study is to evaluate the efficacy of ATB-346 in reducing pain at three doses (versus control) and establish the lowest effective dose. The profile of each ATB-346 dosing cohort will be finalized based on the findings of the above-mentioned metabolism protocol. A top-line data read-out from this study is anticipated in second quarter of 2019.  Antibe expects that the full Phase 2 study with the metabolism protocol will cost roughly $3 million and will be funded with cash-on-hand. Clinical studies have indicated that ATB-346 is much more potent than naproxen and proposes that that one or more active metabolites contribute to the mechanism of action.  +++++  Well that wraps up another episode of Biotechnology Focus radio. Thanks for listening! Hope you all had a chance to get outside this past long weekend and take advantage of what’s left of summer. Maybe innovation will strike, and it will be your story I’m reading next! For the stories in full, check them out at biotechnologyfocus.ca. Until next time, from my desk to yours – this is Michelle Currie.  

Prof Bradley Monk talks to ecancer at the 2013 ESGO meeting in Liverpool about a phase III, randomised trial with pacitaxel plus trebanaib in recurrent ovarian cancer. Trebananib is an anti-angiogenesis peptibody that inhibits the binding of angiopoietin 1/2 to the Tie2 receptor. The trial reported that trebananib prolonged progression free survival by 52% and had an increased response rate from 30% to 38%.

We assessed whether Angiopoietin-2 (Ang2), a Tie2 ligand and partial antagonist of Angiopoietin-1 (Ang1), is required for early vessel destabilization during postischemic angiogenesis, when combined with vascular growth factors. In vitro, matrigel co-cultures assessed endothelial-cell tube formation and pericyte recruitment after stimulation of VEGF-A, Apelin (APLN), Ang1 with or without Ang2. In a murine hindlimb ischemia model, adeno-associated virus (rAAV, 3×10(12) virusparticles) transduction of VEGF-A, APLN and Ang1 with or without Ang2 (continuous or early expression d0-3) was performed intramuscularly (d-14). Femoral artery ligation was performed at d0, followed by laser doppler perfusion meassurements (LDI) 7 and 14. At d7 (early timepoint) and d14 (late timepoint), histological analysis of capillary/muscle fiber ratio (CMF-R, PECAM-1) and pericyte/capillary ratio (PC-R, NG2) was performed. In vitro, VEGF-A, APLN and Ang1 induced ring formation, but only APLN and Ang1 recruited pericytes. Ang2 did not affect tube formation by APLN, but reduced pericyte recruitment after APLN or Ang1 overexpression. In vivo, rAAV.VEGF-A did not alter LDI-perfusion at d14, consistent with an impaired PC-R despite a rise in CMF-R. rAAV.APLN improved perfusion at d14, with or without continuous Ang2, increasing CMF-R and PC-R. rAAV.Ang1 improved perfusion at d14, when combined with rAAV.Ang2 (d0-3), accompanied by an increased CMF-R and PC-R. The combination of early vessel destabilization (Ang2 d0-3) and continuous Ang1 overexpression improves hindlimb perfusion, pointing to the importance of early vessel destabilization and subsequent vessel maturation for enhanced therapeutic neovascularization.

Targeting the Angiopoietin-Tie2 axis is a promising alternative antiangiogenic strategy for the treatment of ovarian cancer that exhibits non-overlapping toxicities with inhibitors of the VEGF signaling pathway.

Cytomegalovirus (CMV) is frequently transmitted by solid organ transplantation and is associated with graft failure. By forming the boundary between circulation and organ parenchyma, endothelial cells (EC) are suited for bidirectional virus spread from and to the transplant. We applied Cre/loxP-mediated green-fluorescence-tagging of EC-derived murine CMV (MCMV) to quantify the role of infected EC in transplantation-associated CMV dissemination in the mouse model. Both EC- and non-EC-derived virus originating from infected Tie2-cre(+) heart and kidney transplants were readily transmitted to MCMV-naïve recipients by primary viremia. In contrast, when a Tie2-cre(+) transplant was infected by primary viremia in an infected recipient, the recombined EC-derived virus poorly spread to recipient tissues. Similarly, in reverse direction, EC-derived virus from infected Tie2-cre(+) recipient tissues poorly spread to the transplant. These data contradict any privileged role of EC in CMV dissemination and challenge an indiscriminate applicability of the primary and secondary viremia concept of virus dissemination.