Squid: Coming to Life—images and video captured the MBL Embryology course between 2007 and 2016. Produced by former course co-director Nipam Patel, UC Berkeley.
Reporter: Aviva lev-Ari, PhD, RN
Archive for December, 2016
Squid: Coming to Life—images and video captured the MBL Embryology course between 2007 and 2016. Produced by former course co-director Nipam Patel, UC Berkeley.
Posted in Biological Networks, Gene Regulation and Evolution on December 16, 2016| Leave a Comment »
Technion Integrated Cancer Center (TICC): Turning Big Ideas into Action
Posted in CANCER BIOLOGY & Innovations in Cancer Therapy on December 16, 2016| Leave a Comment »
Technion Integrated Cancer Center (TICC): Turning Big Ideas into Action
Reporter: Aviva Lev-Ari, PhD, RN
www.ats.org/cancer
Technion Integrated Cancer Center (TICC): Turning Big Ideas into Action
Compelling philanthropic initiatives often sound simple.
End child hunger. Educate all people. Spread clean water access. Help earthquake victims. Improve health care. Cure cancer.
But these bold objectives are not simple. These are big, complex ideas requiring tremendous resources that research universities are often best equipped to harness. Philanthropy is one of the key resources needed. We at ATS don’t actually execute these initiatives—but we play the critical role of translating the big ideas into action by connecting the diverse and sometimes disparate groups of people who can accomplish these far-reaching goals together.
In other words, we don’t solve the problem: we enable the Technion to assemble the team that can solve the problem. It’s a subtle but important distinction that was brought to life earlier this month, as we marked the opening of the Technion Integrated Cancer Center, a first-of-its-kind institution that brings together world-class clinical experts, a group of life science researchers led by a Nobel Prize winner, and top-level chemists, physicists and engineers to win the battle against cancer.
The TICC serves as a nexus for the Technion’s five affiliated hospitals that run clinical trials, the Rappaport Faculty of Medicine’s life sciences researchers, the Faculty of Computer Science’s innovations in processing large data sets, the Viterbi Faculty of Electrical Engineering’s and the Faculty of Physics’ development of devices for diagnosis and imaging, and the Faculty of Mathematics’ search for new, more powerful algorithms to quickly and effectively process complex data.
(l to r) Prof. Ze’ev Ronai, Co-Director of the TICC; Technion President Professor Peretz Lavie; Yona Yahav, Mayor of Haifa; Distinguished Professor Aaron Ciechanover, Co-Director of the TICC; Prof. Rafi Beyar, Director of the Rambam Healthcare Campus
Cancer is one of the greatest challenges of humankind today. In the U.S. alone, with its population of 300 million people, there are 1.5 million new cancer patients every year, causing 300,000 deaths. When I spoke with TICC Co-Director Ze’ev Ronai, he emphasized that harnessing the power of diverse, accomplished researchers and practitioners is essential to advancing our ability to combat cancer.
“We have quite a few ideas about how to combat this disease, but translating those ideas into actual drugs is not easy. We have to determine if the drugs work by finding the right patient population because not all patients will respond to certain drugs. And we need to develop new strategies to determine who those patients are,” Ronai said. “We used to develop the same drugs to attack cancer, but we now know that cancer is complex and heterogeneous. Our drugs need to be smart enough to attack the different elements of each different type of cancer.”
SOURCE
At 95, Thomas Schelling died, 2005 Nobel Prize in Economics and Contributor to Game Theory as an Academic Discipline and tool in Strategic Studies
Posted in Interviews with Scientific Leaders on December 15, 2016| Leave a Comment »
At 95, Thomas Schelling died, 2005 Nobel Prize in Economics and Contributor to Game Theory as an Academic Discipline and tool in Strategic Studies
Reporter: Aviva Lev-Ari, PhD, RN
WordCloud Image Produced by Adam Tubman
Thomas Schelling’s Lecture in 12/2005 – Nobel Prize Laureate in Economics
http://www.nobelprize.org/mediaplayer/index.php?id=626
Thomas C. Schelling – Facts
Photo: T. Zadig
Thomas C. Schelling
Born: 14 April 1921, Oakland, CA, USA
Died: 13 December 2016, Bethesda, MD, USA
Affiliation at the time of the award: University of Maryland, Department of Economics and School of Public Policy, College Park, MD, USA
Prize motivation: “for having enhanced our understanding of conflict and cooperation through game-theory analysis”
Field: game theory
Contribution: A creative application of game theory to important social, political and economic problems. Showed that a party can strengthen its position by overtly worsening its own options, that the capability to retaliate can be more useful than the ability to resist an attack, and that uncertain retaliation is more credible and more efficient than certain retaliation. These insights have proven to be of great relevance for conflict resolution and efforts to avoid war.
Prize share: 1/2
SOURCE
http://www.nobelprize.org/nobel_prizes/economic-sciences/laureates/2005/schelling-facts.html
Thomas Schelling, Nobelist and game theory pioneer, 95
Was co-founder of Harvard Kennedy School, Weatherhead Center
WATCH the VIDEO
More on Thomas Schelling Life and Accomplishments
Reduction in Mortality in Breast Cancer Patients: Outcome of Drug Interactions
Posted in Cancer and Current Therapeutics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Genomics, Cancer Informatics, Genomic Expression on December 14, 2016| Leave a Comment »
Reduction in Mortality in Breast Cancer Patients: Outcome of Drug Interactions
Reporter: Aviva Lev-Ari, PhD, RN
Drug interactions using gene-expression data: common molecular pathways that might account for drug pairs with apparent synergistic effects, searching for drug-protein interactions in the twoXAR company’s database.
“This is a holistic look at the data — EHR, gene expression, protein targets of drugs — all in one analysis,”
Study reveals drug interactions that may reduce mortality in breast cancer patients
Stanford researchers found that certain drug combinations were associated with lower mortality rates among breast cancer patients, pointing to potential drug targets and new ways of thinking about known diseases.
DEC 9 2016
Nigam Shah
Patient health records revealed two drug combinations that may reduce mortality rates in breast cancer patients, according to a study led by researchers at the Stanford University School of Medicine.
The drugs involved were commonly used noncancer drugs that turned out to be associated with a longer average survival rate in breast cancer patients.
The study was published online Dec. 9 in the Journal of the American Medical Informatics Association. The lead author is Stanford postdoctoral scholar Yen Low, PhD. The senior author is Nigam Shah, MBBS, PhD, associate professor of medicine and of biomedical data science.
“So we ran the analysis, and we found a few drug combinations that seemed to associate with better survival,” said Shah.
‘How do we know it’s true?’
Specifically, there were three pairs of drug types. The two combinations in Red are impplicated with improved survivability.
- anti-inflammatory drugs, such as aspirin or naproxen, and blood-lipid modifiers, such as statins;
- lipid modifiers and drugs such as fluticasone used to treat asthma like conditions; and
- anti-inflammatories and anti cancer hormone antagonists — typically, drugs that suppress the synthesis of estrogen.
SOURCE
CHI’s Combination Immunotherapy Design Models, February 20-22, 2017, Moscone North Convention Center, San Francisco, CA – part of the 24th International Molecular Medicine Tri-Conference
Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Conference Coverage with Social Media, Genome Biology, Immuno-Oncology & Genomics, Immunotherapy on December 14, 2016| Leave a Comment »
CHI’s Combination Immunotherapy Design Models, February 20-22, 2017, Moscone North Convention Center, San Francisco, CA – part of the 24th International Molecular Medicine Tri-Conference
Reporter: Aviva Lev-Ari, PhD, RN
Cambridge Healthtech Institute’s Fifth Annual
Combination Immunotherapy Design Models
Preclinical Approaches and Biomarkers to Bring Combination Therapies to the Clinic
February 20-22, 2017 | Moscone North Convention Center | San Francisco, CA
Part of the 24th International Molecular Medicine Tri-Conference
Despite tremendous progress in our understanding of cancer biology, the majority of novel anticancer therapies fail in clinical trials, which indicates deficiencies in conventional translational approaches. In most cases preclinical data have overpredicted clinical efficacy in oncology. With the rise of immuno-oncology the challenge of in vivo pharmacology was enhanced by the differences in mouse and human immune systems that further damages the predictiveness of preclinical data. The phenomenon of cancer heterogeneity and subsequent drug resistance add another dimension to the preclinical cancer research warranting active work on combination cancer regimens. Better models and approaches are clearly in high and urgent demand and has been worked on by industry and academia scientists. Cambridge Healthtech Institute’s Fifth Annual Translational Models in Oncology and Immuno-Oncology conference is designed to highlight cutting edge advances in in vivo, in vitro and in silico modeling and to facilitate a discussion about effective translational approaches in cancer research.
Day 1 | Day 2 | Day 3 | Download Brochure
You may be interested in these related Tri-Conference short courses:
SC5: Genomics in Drug Discovery and Development: Pharmaceutical Applications of NGS
SC13: Humanized Mouse Models for Pre-Clinical Assessment of Cancer Immunotherapy
SC20: Translating Preclinical Data in the Rational Design of Cancer Combination Therapies
SC24: Flow Cytometry and Phenotypic Cell Analysis in Immuno-Oncology
10:30 am Conference Program Registration Open
TRANSLATIONAL IMMUNO-ONCOLOGY
11:50 Chairperson’s Opening Remarks
Terri McClanahan, Ph.D., Executive Director, Molecular Discovery, Biologics, Merck Research Laboratories
12:00 pm KEYNOTE PRESENTATION: Rational Development of Combination Therapies in Immuno-Oncology
Michael Kalos, M.D., CSO, Cancer Immunobiology, Eli Lilly
Treatment of patients with combinations of agents, such as CTLA4 and PD1, has provided additional benefit to patients, along with increased toxicity, highlighting the value for developing combination therapies. In this session, we will discuss preclinical and translational strategies and approaches to support the rational development of more effective combination strategies that lead to increased clinical benefit for patients.
12:30 Biomarker Development for the Era of Combination Cancer Immunotherapy
Terri McClanahan, Ph.D., Executive Director, Molecular Discovery, Biologics, Merck Research Laboratories
Keytruda® (pembrolizumab), a PD-1-specific monoclonal antibody, is approved in the U.S. for advanced melanoma, NSCLC and SCCHN, and is being studied in >30 cancers. Efforts are now underway to extend the benefit of cancer immunotherapy to more patients through the use of anti PD-1-based combination regimens. However, significant challenges remain to identify the best combinations that provide true immune synergy, and to target the right combinations to the right patients who will experience unambiguous clinical benefit. Biomarker and translational research-driven strategies can guide the future state of the field, ultimately allowing for the development of precision medicine approaches to combination cancer immunotherapy.
1:00 Session Break
1:10 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
2:10 Session Break
TRANSLATIONAL IMMUNO-ONCOLOGY (CONT.)
Christian Gerdes, Ph.D., Head, Pharmacology, Roche Pharma Research & Early Development, Roche
2:40 Immunocompetent Mouse Models as a Tool for Cancer Immunotherapy Pipeline Advancement
Christian Gerdes, Ph.D., Head, Pharmacology, Roche Pharma Research & Early Development, Roche
As immunotherapy gains more and more traction, the need for more predictive preclinical models grows as well. It is widely recognized that immunocompetent mice are used to assess the anti-tumor efficacy of cancer immunotherapies. This presentation will discuss the uses of mouse models and how they can advance drug pipelines.
3:10 Designing and Executing Cancer Immunotherapy Clinical Trials
Pamela N. Munster, M.D., Professor, Medicine, Program Leader, Development Therapeutics, Director, Early Phase Clinical Trials Program, Helen Diller Cancer Center, University of California, San Francisco
A breakdown in immune tumor surveillance plays a crucial role in the development of metastatic cancer. Targeting the programmed death receptor (PD-1) and its ligand (PD-L1) have been major breakthroughs in certain cancers such melanoma, lung and other cancers. However, many cancers, including breast cancers, appear less responsive. We are exploring the roles of tumor lymphocyte infiltration, T cell differential, epigenetic modifiers and the co-operative involvement of other immune pathways to induce responses in immune silent tumors. Translating preclinical findings into early phase clinical studies, we will describe recent advances in how to determine safety, feasibility and efficacy of integrating immunotherapy into targeted therapy and chemotherapy.
3:40 Talimogene Laherparepvec in Combination with Checkpoint Inhibitors: From Bench to Bedside
Pedro J. Beltran, Ph.D., Research Director, Oncology Research, Amgen, Inc.
Checkpoint inhibitors and viral immunotherapy with talimogene laherparepvec have shown significant therapeutic benefit in melanoma patients when used as monotherapies. As these two forms of approved immunotherapy act mostly on different parts of the immunity cycle, studying their combination pre-clinically and clinically informs their future development. We have used 3 syngeneic murine models to study the pharmacodynamic and efficacy changes driven by the combination of talimogene laherparepvec and blockade of CTLA-4 or PD-1/PD-L1. Clinical trials testing these combinations in the clinic are currently ongoing.
4:10 Presentation to be Announced
4:25 Sponsored Presentation (Opportunity Available)
4:40 Refreshment Break and Transition to Plenary Session
6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing
7:30 Close of Day
Day 1 | Day 2 | Day 3 | Download Brochure
TUESDAY, FEBRUARY 21
7:30 am Registration Open and Morning Coffee
9:00 Refreshment Break in the Exhibit Hall with Poster Viewing
TUMOR MODELS FOR CANCER IMMUNOTHERAPY
10:05 Chairperson’s Remarks
Gavin Thurston, Vice President, Oncology and Angiogenesis Research, Regeneron Pharmaceuticals
10:15 Mouse Models to Test Human Cancer Immuno-Therapeutics
Gavin Thurston, Vice President, Oncology and Angiogenesis Research, Regeneron Pharmaceuticals
Preclinical in vivo tumor models are essential to test anti-tumor activity and side-effect profiles of novel immunotherapeutics. However, antibody-based therapies often do not cross-react with the corresponding murine targets, making such tests difficult. We have utilized Regeneron’s capabilities in murine genetic engineering to develop several approaches of combining functional immune cells with preclinical tumor models. We have used these approaches for preclinical testing of both checkpoint inhibiting antibodies and T cell-engaging bispecific antibodies.
10:45 Characterization of Molecular and Cellular Properties of Murine Syngeneic Models to Aid Model Selection and Biomarker Discovery for Immune-Oncology Programs
Wenyan Zhong, Ph.D., Senior Principal Scientist, Oncology R&D Group, Pfizer
Preclinical in vivo models for most immuno-oncology (IO) programs require the use of immunocompetent mice bearing syngeneic tumors. To facilitate model selection for use in preclinical efficacy studies, we characterized a panel of mouse tumor cell lines and syngeneic tumor tissues. In this talk, we will discuss molecular and cellular properties of these models.
11:15 Case Study: Blockade of Phosphatidylserine-Mediated Tumor Immune Suppression to Enhance Immune Checkpoint Therapies
Michael Gray, Ph.D., Senior Research Scientist, Peregrine Pharmaceuticals
Phosphatidylserine (PS) exposure in tumors induces non-inflammatory signals which contribute to an immunosuppressive environment. Antibody blockade of PS activates immune responses by promoting M1 macrophages, maturation of dendritic cells and inducing adaptive T-cell responses. PS targeting antibodies enhance the anti-tumor activity of checkpoint antibodies in preclinical tumor models.
11:45 Methods and Models for Preclinical Immuno-Oncology
Dylan Daniel, Ph.D., Director, Scientific Development, MI Bioresearch
MI Bioresearch has characterized an array of syngeneic immuno-oncology models to support in vivo pharmacology drug discovery. Our characterization includes comprehensive lymphoid and myeloid flow cytometry immune profiling, and model responses to checkpoint inhibitors and focal beam radiotherapy combinations.
12:00 pm 
Genetically Engineered Miniswine Models of Cancer
John Swart, Ph.D., President, Exemplar Genetics
Current preclinical models of cancer fail to accurately recapitulate human disease and do not effectively translated to the clinic. Recently, Exemplar Genetics has developed a genetically engineered miniature swine model that contains a conditional KRAS mutation on the background of TP53-targeted pigs, the ExeGen® TP53+/R167H& KRAS+/G12D miniswine model. This model should allow for the inducement of human-like tumors in a tissue specific manner. Initial characterization of induced tumors demonstrates the transformative nature of this model.
12:30 Session Break
12:35 Luncheon Presentation to be Announced
1:25 Refreshment Break in the Exhibit Hall with Poster Viewing
ADVANCING TRANSLATION WITH NOVEL APPROACHES AND INDUSTRY-ACADEMIA PARTNERSHIPS
2:00 Chairperson’s Remarks
Lawrence B. Schook, Ph.D., Gutsgell Professor, Animal Sciences and Radiology, University of Illinois
2:10 Collaboration for Translation: Academic-Industry Partnerships to Explore Novel Opportunities in the Area of Immuno-Oncology
Joseph Dal Porto, Ph.D., Director, Pfizer Center for Therapeutic Innovation
The Center for Therapeutic Innovation (CTI) -San Francisco is a direct partnership between Pfizer and leading academic institutions, including UC San Francisco, UC San Diego, Stanford University and others, to establish open collaborations designed to rapidly identify targets and develop therapeutic NMEs. The long-term goal is to substantially reduce the time required to translate promising bio-medical research into new medications and therapies. Most recently, CTI has joined with academic oncology and immunology researchers to understand the translatability of emerging targets in the Immuno-Oncology therapeutic arena.
2:40 An Example of a Collaboration between Industry and Academia for Testing Combination Therapies in Preclinical Patient-Derived Xenograft Models of Glioblastoma
Anderson Clark, Ph.D., Director, Translational in vivo Pharmacology, Oncology, EMD Serono Research & Development Institute
John De Groot, Associate Professor, Chair Ad Interim, Neuro-Oncology, The University of Texas MD Anderson Cancer Center
The use of patient-derived xenograft (PDX) models of cancer has increased over the past decade, both in industry and academia, providing preclinical data to support both drug development and basic oncology research.
3:20 The Oncopig Cancer Model (OCM): A Platform for Transitional, Translational and Transformative Advances in Cancer Research
Lawrence B. Schook, Ph.D., Gutsgell Professor, Animal Sciences and Radiology,
University of Illinois
Mammalian models are integral components of basic, translational, and clinical cancer research. Recently, there have been advances in creating large animal transitional porcine cancer models, for use in preclinical and translational research studies with transformational impact for human clinical trials. Pigs, due to their anatomy, physiology, metabolism, and genetics, provide an ideal investigational transitional platform for human clinical trials and offer a critical pathway to narrow gaps in cancer therapy.
3:40 Presentation to be Announced
4:10 Hollywood Oscar Dessert Reception in the Exhibit Hall with Poster Viewing
5:00 Breakout Discussions in the Exhibit Hall
These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion. Pre-registration to sign up for one of the topics will occur a week or two prior to the Event via the App.
Humanized Mouse Models
Gavin Thurston, Vice President, Oncology and Angiogenesis Research, Regeneron Pharmaceuticals
- Appropriate applications of humanized mouse models in immuno-oncology
- Limitations of current models
- Areas of future development
Next Generation Cellular Models
Scott Martin, Senior Scientific Manager, Group Lead, Functional Genomics, Discovery Oncology, Genetech Inc.
- Cancer cell line profiling
- Large-scale genomic and drug response screening
- Future directions
Biomarkers for Cancer Combination Design
Jianda Yuan, M.D., Ph.D., Director, Translational Immuno-Oncology Research, Early Clinical Oncology Development, Merck & Co., Inc.
- Validation of biomarkers before use in clinical care
- Using prognostic and predictive biomarkers for enrichment and stratification factors in drug development
- Challenges and Implementation of biomarkers into clinical practice
6:00 Close of Day
Day 1 | Day 2 | Day 3 | Download Brochure
WEDNESDAY, FEBRUARY 22
7:00 am Registration Open
7:00 Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee
10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall
TRANSLATIONAL BIOMARKERS IN CANCER IMMUNOTHERAPY DEVELOPMENT
10:50 Chairperson’s Remarks
Jianda Yuan, M.D., Ph.D., Director, Translational Immuno-Oncology Research, Early Clinical Oncology Development, Merck & Co., Inc.
11:00 Next Generation Biomarkers for the Era of Combination Cancer Immunotherapy
Jianda Yuan, M.D., Ph.D., Director, Translational Immuno-Oncology Research, Early Clinical Oncology Development, Merck & Co., Inc.
Sarah Javaid, Ph.D., Senior Scientist, Discovery Pharmacogenomics, Genetics and Pharmacogenomics, Merck & Co., Inc.
Combination approaches are the keys to improving clinical response. From preclinical immune-oncology mouse models to patients enrolled on clinical trials, novel high throughput technologies enable us to understand the mechanisms underlying the complex interactions between the immune system and cancer, identify predictive biomarkers for the patients who will most likely benefit from current immunotherapies, avoid immune-related adverse events and guide the future combination cancer immunotherapy.
11:30 High-Content Molecular Profiling in Preclinical Immuno-Oncology Research
Ruslan Novosiadly, Senior Research Advisor, Cancer Immunobiology, Biomarkers, Eli Lilly
Recent clinical data have revealed the remarkable potential for T cell modulating agents to induce potent and durable responses in a subset of cancer patients. In this presentation, we discuss molecular approaches, platforms and strategies that enable a broader interrogation of the activity of agents that modulate the activity of tumor-specific T cells as well as examples of data sets generated in preclinical studies that have provided important insights into the biological activity of T cell therapies and support further rational development of this exciting treatment modality.
12:00 pm Utility of Quantifying Circulating Lymphocyte Populations as Pharmacodynamic Biomarkers in Trials of Immune Oncology Therapeutics
Nathan Standifer, Ph.D., Scientist II, Clinical Pharmacology and DMPK, MedImmune
Immune oncology (IO) therapeutics are directed at inducing immune responses against tumor cells. Intrinsic to this mechanism of action is the activation of circulating immune cells, which can be most effectively monitored using flow cytometry-based assays. In this presentation, aspects of assay development, validation, implementation and analysis of clinical flow cytometry datasets will be discussed. Results from clinical trials of IO as single agents or in combination with other IO will be shown and strategies for interpretation and post-hoc analyses will be detailed.
12:30 Session Break
12:40 Luncheon Presentation to be Announced
1:10 Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing
CELLULAR MODELS FOR COMBINATION THERAPY DESIGN
1:50 Chairperson’s Remarks
Scott Martin, Senior Scientific Manager, Group Lead, Functional Genomics, Discovery Oncology, Genetech
2:00 Understanding and Predicting Cellular Response through Chemical and Functional Genomic Profiling of Well-Characterized Cancer Cell Lines
Scott Martin, Senior Scientific Manager, Group Lead, Functional Genomics, Discovery Oncology, Genetech
Determining relationships between genomic features and drug sensitivity is central to the concept of personalized medicine and indication selection. Many studies have highlighted the value of integrating omics data with drug activity across cell lines to identify predictors of response. Here we extend upon these studies with numerous chemical and genetic perturbations to explore such relationships. Data reveals both known and novel correlations, and was also used to explore best experimental and computational practices.
2:30 Beyond Genomics: Identifying Treatment Options for Refractory Cancer Patients Using Real Time Functional Assays and FDA Approved Drug Combinations
Matthew De Silva, CEO, Founder, Notable Labs
Refractory cancer patients often have resistant disease that does not respond to single agent therapy. Combination strategies are promising, but patient heterogeneity makes clinical trial design difficult. Next generation functional phenotypic assays using a patient’s cancer cells can identify potentially synergistic treatments in a matter of days, but the combinatorial space is often larger than the available cells. In silico models that employ ‘omic data from a patient can prioritize which combinations to test ex vivo. If the agent(s) of choice are approved, physicians can then prescribe them
3:00 Generation of ex vivo Tumor Models from PDX Tumors as a Platform for Clinically Relevant Anticancer Drug Discovery
Geoffrey A. Bartholomeusz, Ph.D., Associate Professor and Director, siRNA Core Facility, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Monolayer cell cultures platforms inadequately represent the complex tumor microenvironment and drugs identified by these systems have failed when translated into the clinics. Clinically relevant PDX systems are both costly and time consuming. We have developed a clinically relevant ex vivo tumor tissue system derived from a PDX tumor, and preliminary data confirms its potential to serve as a platform for clinically relevant drug discovery in a time and cost effective manner.
3:30 Session Break
CRISPR FOR TUMOR MODELING, INTERNATIONAL INITIATIVES
3:40 Chairperson’s Remarks
Monte Winslow, Ph.D., Assistant Professor, Genetics, Stanford University
3:45 Cancer Modeling with in vivo CRISPR/Cas9 Genome Editing
Monte Winslow, Ph.D., Assistant Professor, Genetics, Stanford University
Conventional genetically engineered mouse models of human cancer have been instrumental in our understanding of all aspects of cancer development. However, these models are much too labor-intensive, expensive, and slow to perform the extensive molecular analyses needed to adequately comprehend this disease. I will discuss our ongoing work to employ CRISPR/Cas9-mediated genome editing to generate cancer models and illuminate gene function during cancer progression within the natural in vivo setting.
4:15 Tailored Pre-Clinical Models with CRISPR-Based Genome Editing
Lukas Edward Dow, Assistant Professor, Medicine, Weill Cornell Medicine
CRISPR/Cas9 genome editing has changed the way we design and execute in vivo experiments. We are using CRISPR-based genome editing in stem cells and in adult mice to generate tailored pre-clinical models. This allows both a deeper understanding of the genetic underpinnings of cancer progression and provides a platform to interrogate new therapeutic strategies in specific genetic contexts, which is key for realizing the potential of personalized medicine.
4:45 The Human Cancer Model Initiative
Louis M. Staudt, M.D., Ph.D., Director, Center for Cancer Genomics, Co-Chief, Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health
The Human Cancer Model Initiative (HCMI) aims to generate 1000 new cancer cell lines directly from patient biopsy material using a variety of technologies, including organoids and conditionally reprogrammed cells. Each cell line will be genomically characterized and clinical diagnostic and therapeutic data will be gathered from the participating patients. The new cell lines and their associated data will be made available to the research community to promote a deeper understanding of cancer and its response or resistance to therapy.
5:15 Close of Conference Program
SOURCE
http://www.triconference.com/Pre-Clinical-Oncology-Models/
From: Marina Filshtinsky <pete@healthtech.com>
Date: Wednesday, December 14, 2016 at 10:00 AM
To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>
Subject: Combination Immunotherapy Design Models
Li -Fraumeni Syndrome and Pancreatic Cancer
Posted in Cancer Screening, Cell Biology, Genome Biology, Genomic Testing: Methodology for Diagnosis, Li-fraumeni syndrome., Mutagenesis, TP53 - Germline mutations, Variation in human protein-coding regions, tagged gene therapy, Li-fraumeni syndrome., Pancreatic cancer, PRIMA-1, TP53 on December 14, 2016| Leave a Comment »
Li -Fraumeni Syndrome and Pancreatic Cancer
Curator: Marzan Khan, B.Sc.
Li-Fraumeni syndrome (LFS) is a condition that makes individuals prone to developing a wide variety of cancers that occur early on in life, the most common types being- soft tissue sarcoma, osteosarcoma, breast cancer, brain tumors, adrenocortical carcinoma (ACC), and leukemia. (1) Pancreatic cancer is minimally associated with the condition. (2) A survey found the presence of pancreatic cancer in only 1% of 475 tumor samples collected from 91 families who were carriers of p53 mutations, with half of them having LFS. The incidence of breast cancer amongst them was the highest -24%. (2) Pancreatic carcinoma in LFS patients usually occurs in the later stages of life. (3)
The underlying cause of LFS is germline mutations in TP53 gene on chromosome 17p, that encodes the transcription factor p53, crucial in cell cycle regulation and the repair of damaged and/or abnormal cells. (4) In the majority of cases, this mutation is obtained by inheritance. (5) De-novo germline mutations in p53 occur in 7%-20% of the cases. (5)
A person showing symptoms of any type of cancer at an early age or having first or second-degree relatives with cancer are at risk of developing LFS. (5) That is why tracing family history is an important part of diagnosis in LFS patients. Genetic testing can confirm mutations present in the gene, however, there are controversial ethical issues regarding their use, particularly in children and fetuses.
In patients with LFS, it is important to control the manifestations of the disease. They should be monitored closely so that any new cancers that arise are diagnosed and treated during the early stages. (6) Patients are also at risk of developing radiation-induced second and third primary tumors. (6) Therefore, radiation and alkylating agents should be used minimally (6) People at risk can be cautioned to avoid exposure to carcinogens such as sunlight, cigarette smoke, and alcohol consumption. (5) Therapeutic approaches that are aimed at restoring wild-type p53 by gene therapy as well as reactivating non-functional p53 by the use of small-molecule drugs are currently being investigated in many cancers. (7) Unlike radiation therapy, these small-molecule drugs are non-toxic to healthy cells, thus eliminating the risk of forming new tumors.
So far, PRIMA-1 has proven to be quite effective at correcting non-functional p53. (8) PRIMA-1 is changed to its methylated form, PRIMA-1MET that forms covalent adducts to thiol groups in the mutated protein and modifies them. (8) As a result, p53 regains its ability to destroy malignant cells. (8) A research study also found that PRIMA-1 induces apoptosis and increases the sensitivity of pancreatic cancer cells to various chemotherapeutic agents. (9)
- Magali Olivier, David E. Goldgar, Nayanta Sodha, Hiroko Ohgaki, Paul Kleihues, Pierre Hainaut and Rosalind A. Eeles. Li-Fraumeni and Related Syndromes. Cancer Res October 15 2003 63 (20) 6643-6650 http://cancerres.aacrjournals.org/content/63/20/6643.abstract
- Kleihues P, Schauble B, zur Hausen H, et al. Tumors associated with p53 germline mutations: a synopsis of 91 families. Am J Pathol 1997; 150:1-13 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1858532/
- John P. Neoptolemos, Raul Urrutia, James L. Abbruzzese, Markus W. Buchler. Pancreatic Cancer. 2010.1st ed, pp-6, 2010, Springer, Verlag, New York
- Mishra B and Patel RR. Gene Therapy for Treatment of Pancreatic Cancer. Austin Therapeutics. 2014;1(1): 10. https://books.google.ca/books?id=NmBB5ZoKkk4C&pg=PA6&lpg=PA6&dq=connection+between+li+fraumeni+and+Pancreatic+cancer&source=bl&ots=H0iCeaPP0N&sig=pqJT1tPMR6C-NIig3S_NkFKFsD0&hl=en&sa=X&ved=0ahUKEwi4nLrgzuPQAhUUIWMKHS3wBoc4ChDoAQhNMAg#v=onepage&q=connection%20between%20li%20fraumeni%20and%20Pancreatic%20cancer&f=false
- Schneider K, Zelley K, Nichols KE, et al. Li-Fraumeni Syndrome. 1999 Jan 19 [Updated 2013 Apr 11]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. https://www.ncbi.nlm.nih.gov/pubmed/20301488
- Elisa Becze BA, ELS, 2011 Mar 1. An introduction to Li-Fraumeni Syndrome, Five-Minute-In-Service. http://connect.ons.org/columns/five-minute-in-service/an-introduction-to-li-fraumeni-syndrome
- Sorrell, A. D., Espenschied, C. R., Culver, J. O., & Weitzel, J. N. (2013).TP53Testing and Li-Fraumeni Syndrome: Current Status of Clinical Applications and Future Directions. Molecular Diagnosis & Therapy, 17(1), 31–47. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627545/
- Emily J. Lewis. PRIMA-1 as a cancer therapy restoring mutant p53: a reviewBioscience Horizons (2015) 8: hzv006 http://biohorizons.oxfordjournals.org/content/8/hzv006.full
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Other related articles published in this Online Scientific Journal include the following:
p53 mutation – Li-Fraumeni Syndrome – Likelihood of Genetic or Hereditary conditions playing a role in Intergenerational incidence of Cancer
Reporter: Aviva Lev-Ari, PhD, RN
Pancreatic Cancer: Articles of Note @PharmaceuticalIntelligence.com
Curator: Aviva Lev-Ari, PhD, RN
Advanced Peripheral Artery Disease (PAD): Axillary Artery PCI for Insertion and Removal of Impella Device
Posted in Assist Devices: LV, Atherogenic Processes & Pathology, Cardiac & Vascular Repair Tools Subsegment, Cardiac and Cardiovascular Surgical Procedures, Frontiers in Cardiology and Cardiovascular Disorders, Mechanical Assist Devices: LVAD, PCI, Peripheral Arterial Disease & Peripheral Vascular Surgery on December 13, 2016| Leave a Comment »
Advanced Peripheral Artery Disease (PAD): Axillary Artery PCI for Insertion and Removal of Impella Device
Reporter: Aviva Lev-Ari, PhD, RN
TOTALLY PERCUTANEOUS INSERTION AND REMOVAL OF IMPELLA DEVICE USING AXILLARY ARTERY IN THE SETTING OF ADVANCED PERIPHERAL ARTERY DISEASE
July 15, 2016
Abstract: Traditionally, brachial and common femoral arteries have served as access sites of choice, with many operators recently converting to radial artery access for coronary angiography and percutaneous intervention due to literature suggesting reduced bleeding risk, better patient outcomes, and lower hospital-associated costs. However, radial access has limitations when percutaneous procedures requiring larger sheath sizes are performed. Six Fr sheaths are considered the limit for safe use with the radial artery given that the typical luminal diameter of the vessel is approximately 2 mm, while peripheral artery disease (PAD) may often limit use of the common femoral artery, particularly in patients with multiple co-morbid risk factors. Similarly, the brachial artery has fallen out of favor due to both thrombotic and bleeding risks, while also not safely and reliably accommodating sheaths larger than 7 Fr. Here we describe 3 cases of a new entirely percutaneous technique utilizing the axillary artery for delivery of Impella 2.5 (13.5 Fr) and CP (14 Fr) cardiac-assist devices for protected percutaneous coronary intervention in the setting of prohibitive PAD.
J INVASIVE CARDIOL 2016;28(9):374-380. 2016 July 15 (Epub ahead of print)
Key words: axillary artery, percutaneous access, high-risk PCI
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