Category Archives: Molecular Medicine

A three-drug chemo cocktail appears to shrink tumors and improve survivorship among pancreatic cancer patients, a new, small study shows.

Tumors substantially shrank for just over 71% of patients treated with a three-drug regimen of nab-paclitaxel, gemcitabine, and platinum-based cisplatin, the researchers found.

Further, 16 patients (64%) out of the 25 treated were still alive a year after treatment, more than double the average 26% one-year survival rate for people with advanced pancreatic cancer.

Ten patients (40%) were still alive after two years, a survival rate unheard of for patients with stage 4 pancreatic cancer, said senior researcher Dr. Daniel Von Hoff. He's director of the Translational Genomics Research Institute's molecular medicine division, in Phoenix.

All three drugs have been approved by the U.S. Food and Drug Administration for chemotherapy. Nab-paclitaxel and gemcitabine are the current front-line chemo combo used to treat pancreatic cancer, the study authors noted.

For the study, the researchers added low doses of platinum-based cisplatin to that usual combo, based on laboratory evidence that cisplatin inhibited the ability of pancreatic cancer cells to repair their DNA, causing them to self-destruct.

"We had preclinical evidence that these tumors have significant trouble repairing DNA damage, so throwing in a little something that causes DNA damage in a tumor would hopefully push it a little further," Von Hoff said.

Tumors wound up shrinking in seven of every 10 patients, nearly triple the usual response rate of 26%, Von Hoff said.

The researchers described the additional side effects as "tolerable," involving mainly blood-related conditions that were manageable.

About two-thirds of the patients experienced a decrease in platelets, the blood cells that help clotting, and one-third developed anemia from a reduction in the red blood cells that carry oxygen through the body. About one-quarter developed neutropenia, a drop in white blood cells that can impair immune response.

Because cisplatin is a long-standing chemo drug available in generic form, adding the drug should not dramatically increase the cost of cancer treatment, Von Hoff said.

"I wouldn't say it's dirt cheap, but it's pretty cheap," Von Hoff said.

Pancreatic cancer is relatively rare, accounting for about 3% of all cancers in the United States and about 7% of all cancer deaths, according to the American Cancer Society. About 57,000 people will be diagnosed with pancreatic cancer this year, and about 46,000 will die from it.

Based on the study, which was funded by Translational Genomics Research Institute and the HonorHealth Research Institute, Von Hoff expects the three-drug combination will be strongly considered as a potential treatment option by cancer doctors.

Dr. Len Lichtenfeld, interim chief medical officer for the American Cancer Society, agreed that the study will increase interest in this three-drug combo.

"Pancreatic cancer usually presents in an advanced state, requiring chemotherapy, and the chemotherapy options are not particularly good," Lichtenfeld said. "This study of a relatively small number of patients suggests this regimen of currently available drugs appears to be better than the other treatments used for this disease."

However, Lichtenfeld said more study is needed to cement the drug cocktail's results. This study was very small and patients were not chosen at random, so there could be other factors that account for the responses seen here, he said.

Lichtenfeld added that while encouraging, the study does not constitute the sort of revolutionary new treatment seen in other cancers through the innovative use of targeted therapies or immunotherapies.

"I don't think it rises to that level," Lichtenfeld said. "I think through some adjustments of available treatments we have a lot of experience with, the results were better. But is it the breakthrough treatment for pancreatic cancer we all hope for? No, it's not going to rise to that level."

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Drug Trio Highly Effective Against Pancreatic Cancer - Newsmax

Researchers at Western University have shown for the first time the molecular mechanisms at work that cause cannabidiol, or CBD, to block the psychiatric side-effects caused by tetrahydrocannabinol (THC), the main psychoactive chemical in cannabis.

It has been previously shown that strains of cannabis with high levels of THC and low levels of CBD can cause increased psychiatric effects, including paranoia, anxiety, and addictive-behaviors, but why that was occurring was not fully understood.

Steven Laviolette, PhD, and his research team used rats to investigate the role of a molecule in the brains hippocampus called extracellular-signal regulated kinase (ERK) which triggers the neuropsychiatric effects of THC.

Steven Laviolette investigates the role of ERK in the brains hippocampus which triggers the neuropsychiatric effects of THC. Credit: Western University

For years we have known that strains of cannabis high in THC and low in CBD were more likely to cause psychiatric side-effects, said Laviolette, a professor at Westerns Schulich School of Medicine & Dentistry. Our findings identify for the first time the molecular mechanisms by which CBD may actually block these THC-related side-effects.

The research, published in the Journal of Neuroscience demonstrates that rats that were given THC had higher levels of activated ERK, showed more anxiety behaviors and were more sensitive to fear-based learning. Rats that were given both CBD and THC acted like the control rats: they had normal levels of activated ERK, less anxiety behaviors, and were less sensitive to fear-based learning.

Based on these results, the research team proposes that CBD blocks the ability of THC to overstimulate the ERK pathway in the hippocampus and thus prevent its negative side-effects.

PhD Candidate and Vanier Scholar Roger Hudson showed that by co-administering CBD with THC, they were able to reverse the anxiety-like and addictive-like behaviors caused by the THC. Credit: Western University

Our findings have important implications for prescribing cannabis and long-term cannabis use. For example, for individuals more prone to cannabis-related side-effects, it is critical to limit use to strains with high CBD and low THC content, said Laviolette. More importantly, this discovery opens up a new molecular frontier for developing more effective and safer THC formulations.

PhD Candidate and Vanier Scholar Roger Hudson, lead author on the study, says another interesting finding was that CBD alone had no effect on the ERK pathway. CBD by itself had no effect, he said. However, by co-administrating CBD and THC, we completely reversed the direction of the change on a molecular level. CBD was also able to reverse the anxiety-like behavior and addictive-like behavior caused by the THC.

Laviolette says they will be following up these studies by continuing to identify the specific features of this molecular mechanism. The research team will examine ways to formulate THC with fewer side-effects and to improve the efficacy of CBD-derived therapies.

Reference: Cannabidiol Counteracts the Psychotropic Side-Effects of -9-Tetrahydrocannabinol in the Ventral Hippocampus Through Bi-Directional Control of ERK1-2 Phosphorylation by Roger Hudson, Justine Renard, Christopher Norris, Walter J. Rushlow and Steven R. Laviolette, 30 September 2019, Journal of Neuroscience.DOI: 10.1523/JNEUROSCI.0708-19.2019

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Molecular Cannabis Study Reveals How CBD Offsets the Psychiatric Side-Effects of THC - SciTechDaily

Prof Luis Vitetta will deliver his talk, titledMood Disorders and the BrainIntestinal MucosaAppendixMicrobiomeBrain Loopat the event which takes place at the Hilton hotel from October 22-24.

He said: The brain and the gut are connected from early foetal life and the mother's exposure to microbial molecules is thought to exert in utero developmental effects on the foetus. These effects could underpin the groundwork for subsequent pathophysiological mechanisms for achieving immunological tolerance and metabolic equilibrium post birth, events that continue through to 3-4 years of age.

His presentation will focus on how the microbiome promotes cues that instruct the neonate's mucosal tissues and skin in the language of molecular and cellular biology.

It will examine how post-birth mucosal lymphoid tissue formation and maturation (most probably including the vermiform appendix) is microbiota-encouraged and co-establishes the intestinal microbiome with a developing immune system.

Furthermore, Intestinal mucosal tissue maturation loops the brain-gut-brain and is postulated to influence mood dispositions via adverse shifts in the intestinal microbiome phyla, he added.

Key takeaways will include:

From 2007 to 2013 Luis was the Director and Professor of the Centre for Integrative Clinical and Molecular Medicine at the University of Queensland, Faculty of Medicine, based at the Princess Alexandra Hospital in Brisbane.

In 2013 he joined Medlab Clinical, where he now conducts research on the intestinal microbiome in the areas of mood disorders, metabolic diseases, pain and skeletal muscle health. Consequently, Luis has research interests in the microbiome / nutrition / probiotics / prebiotics and mucosal and cellular immunity as well as research on cannabis medicines.

Other confirmed speakers include:

To register, visit:https://www.probiotaasia.com/register/

For sponsorship and commercial partnership queries, please contactSue Ann PehorTim Evans.

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Probiota Asia 2019: Medlab to assess mood disorders and the power of probiotics - FoodNavigator-Asia.com

While AI may increase speed and efficiency of medical care on the front lines, one of its most powerful benefits is the ability to search vast amounts of data to learn about genetic aspects of various diseases.

Cardiomegaly Is An Enlargement Of The Heart Due To Dilatation Of The Heart Cavities. This Can Result From Many Conditions Including A Disease Of The Heart Muscle Myocardial Disease, Defective Valve Function, Or Hypertrophy Of The Heart Muscle Due To

Earlier identification of persons at risk for heart failure or a genetic cardiomyopathy is a prime example. This could enable persons to be more closely monitored by health care providers and even placed on lists for transplant before they decompensate and develop heart failure leading to cardiogenic shock, which can be ultimately be fatal if not treated and identified in a timely fashion.

Researchers at Queen Mary University of London have now harnessed the power of AI to identify patients who are at risk for heart failure, enabling earlier identification, management and treatment of these high-risk individuals.

The research team used an artificial intelligence (AI) technique to analyze cardiac MRI images of 17,000 healthy UK Biobank volunteers. They noted that genetic factors accounted for 22-39% of variation in the size and function of the left ventricle (LV), the main chamber in the heart that pumps blood to the rest of the body. Reduced pumping ability and increase in size of the left ventricle leads to heart failure.

The research, recently published in the journalCirculation, highlights the importance of genetic factors and their role in the contribution to structural heart disease. The investigators discovered 14 specific areas (loci) linked to the dimensions, structure and function of the left ventricle containing genes that control the embryonic development of heart chambers and the contraction of heart muscle.

"It is exciting that the state-of-the-art AI techniques now allow rapid and accurate measurement of the tens of thousands of heart MRI images required for genetic studies, said lead researcher Dr. Nay Aung from Queen Mary University of London in a press release. The findings open up the possibility of earlier identification of those at risk of heart failure and of new targeted treatments; the genetic risk scores established from this study could be tested in future studies to create an integrated and personalized risk assessment tool for heart failure.

"The AI tool allowed us to analyze images in a fraction of the time it would otherwise have taken; this should translate to time and cost savings for the NHS and could potentially improve the efficiency of patient care, he added.

"Previous studies have shown that differences in the size and function of the heart are partly influenced by genes but we have not really understood the extent of that genetic influence,explained co-investigator Steffen Petersen, Professor of Cardiovascular Medicine at Queen Mary University of London. This study has shown that several genes known to be important in heart failure also appear to regulate the heart size and function in healthy people.

That understanding of the genetic basis of heart structure and function in the general population improves our knowledge of how heart failure evolves; the study provides a blueprint for future genetic research involving the heart MRI images in the UK Biobank and beyond, he added.

"High fidelity MRI measures combined with genetics is reassuringly validating many known heart structural proteins, but our work also finds new genes from more heritable functional measures that are associated with ventricular remodeling and fibrosis, added co-investigator Patricia Munroe, Professor of Molecular Medicine at Queen Mary University of London. Further genetic studies including analyses of additional heart MRI chambers are expected to provide deeper insights into heart biology."

In fact, identification of specific genes that play a role in determining left ventricular volume, a key marker of survival in the setting of heart failure (resulting from LV remodeling in the setting of a cardiomyopathy), would be quite valuable. The advent of gene therapy, progenitor cell therapy (stem cells) and emerging molecular genetic approaches to address these genetic anomalies may offer promise.

With the expansion of the UK Biobank database, the expectation is that more genes for cardiac abnormalities will be notified in the future. In fact, UK Biobank announced earlier this month that it will begin sequencing the entire human genome of 450,000 participants, after success of a pilot sequencing trial in 50,000 participants.

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AI Pinpoints Genes Associated With Heart Failure - Forbes

Basel, 30 September 2019 - Roche (SIX: RO, ROG; OTCQX: RHHBY) will today announce positive results from a single-arm cohort of the Phase II/III Blood First Assay Screening Trial (BFAST), the first prospective study to use only blood-based next generation sequencing (NGS) to detect specific fusions with the aim of selecting treatment for people with advanced non-small cell lung cancer (NSCLC), without the need for tissue biopsy. Results from the anaplastic lymphoma kinase (ALK) cohort will be presented at the European Society for Medical Oncology (ESMO) 2019 Congress on Monday 30 September 2019, from 9:15 - 9:30 am CEST (Abstract LBA81 PR), and were also part of the official ESMO press programme.

Obtaining tumour tissue for biomarker testing can be a challenge in many people with cancer and, as a result, some may not receive optimal treatment for their disease, said Sandra Horning, MD, chief medical officer and head of Global Product Development. BFAST is the first trial to show that by using a blood-based next-generation diagnostic, it is possible to identify the ALK mutation in people with non-small cell lung cancer using a blood draw alone, which means that more people could potentially benefit from Alecensa.

Foundation Medicine is pleased to partner with Roche on this study, a first-of-its-kind, pivotal trial that directly demonstrates the clinical utility of using our comprehensive blood-based assay, FoundationOne Liquid, to detect specific fusions and match NSCLC patients with first-line treatment, said Brian Alexander, MD, chief medical officer of Foundation Medicine. Validated and comprehensive liquid biopsy tests are critical to help physicians find the best possible treatment approach for patients with advanced cancer and for whom tissue testing isnt feasible. Identifying ALK fusions can be particularly challenging and these data demonstrate that FoundationOne Liquid can accurately predict which patients can respond to therapy.

The BFAST study used FoundationOne Liquid, Foundation Medicines comprehensive liquid biopsy test, which detects the four main classes of genomic alterations, microsatellite instability (MSI) and select fusions including ALK in circulating tumour DNA (ctDNA) from a blood draw. These data demonstrate that the FoundationOne Liquid assay can help to test and identify a broader population of people with advanced NSCLC who may benefit from Alecensa (alectinib), for whom current diagnostic tests are not suitable, such as for those who cannot provide tissue samples due to insufficient or absent tumour tissue or where tissue diagnostics are not available, and validate the clinical utility of blood-based NGS as an additional method to inform clinical decision-making in ALK-positive NSCLC.

In the study, 87.4% (95% CI: 78.5-93.5) of people with advanced NSCLC who were identified by the FoundationOne Liquid biopsy assay to have ALK fusions had a confirmed response to treatment with Alecensa (overall response rate; ORR) as measured by the investigator per Response Evaluation Criteria in Solid Tumours (RECIST v1.1). This is consistent with the ORR for Alecensa observed in the pivotal Phase III ALEX trial, which identified people using tissue-based testing. When measured using an Independent Review Facility per RECIST v1.1, the confirmed ORR was numerically higher at 92.0% (95% CI: 84.1-96.7). Median progression free-survival (PFS) and duration of response (DoR) were not reached after a median follow-up of 12.6 months. The safety profile of Alecensa was consistent with prior clinical trials and post-marketing experience, with no new safety signals observed.

About the BFAST Study BFAST (Blood First Assay Screening Trial; NCT03178552) is a Phase II/III global, multi-centre, open label, multi-cohort study evaluating the safety and efficacy of targeted therapies or immunotherapies as single agents or in combination in people with unresectable, advanced or metastatic NSCLC determined to harbour oncogenic somatic mutations or be tumour mutational burden (TMB) positive as identified by blood-based NGS ctDNA assays. The Alecensa ALK-positive cohort is the first to readout, with other cohorts due to follow. The primary endpoint for the Alecensa ALK-positive cohort of the BFAST study is confirmed investigator (INV)-assessed ORR. Secondary endpoints include: independent review facility (IRF)-assessed ORR, DoR (INV and IRF), PFS (INV and IRF), overall survival (OS) and safety.

About AlecensaAlecensa (RG7853/AF-802/RO5424802/CH5424802) is a highly selective, CNS active, oral medicine created at Chugai Kamakura Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK-positive. ALK-positive NSCLC is often found in younger people who have a light or non-smoking history. It is almost always found in people with a specific type of NSCLC called adenocarcinoma. Alecensa is now approved in 83 countries as an initial (first-line) treatment for ALK-positive, metastatic NSCLC, including in the US, Europe, Japan and China.

About Foundation Medicine Foundation Medicine is a molecular information company dedicated to a transformation in cancer care in which treatment is informed by a deep understanding of the genomic changes that contribute to each patient's unique cancer. The company, a member of the Roche Group, offers a full suite of comprehensive genomic profiling tests to identify the molecular alterations in a patient's cancer and match them with relevant targeted therapies, immunotherapies and clinical trials. Foundation Medicines molecular information platform aims to improve day-to-day care for patients by serving the needs of clinicians, academic researchers and drug developers to help advance the science of molecular medicine in cancer.

For more information, please visit http://www.foundationmedicine.com or follow Foundation Medicine on Twitter (@FoundationMedicineATCG).

About Roche in lung cancerLung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have five approved medicines to treat certain kinds of lung cancer and more than ten medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

About RocheRoche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve peoples lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the worlds largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the eleventh consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2018 employed about 94,000 people worldwide. In 2018, Roche invested CHF 11 billion in R&D and posted sales of CHF 56.8 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit http://www.roche.com.

All trademarks used or mentioned in this release are protected by law.

Roche Group Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com- Nicolas Dunant (Head)- Patrick Barth- Ulrike Engels-Lange- Daniel Grotzky- Karsten Kleine- Nathalie Meetz- Barbara von Schnurbein

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Roche to present results of first prospective trial using blood-based next generation sequencing which successfully identifies people for treatment...

Researchers at Karolinska Institutet in Sweden have uncovered a chromosome-wide mechanism that keeps the gene expression of sex chromosomes in balance in our cells. The findings shed light on molecular reasons for early miscarriage and could be important for the emerging field of regenerative medicine. The study is published in Nature Structural and Molecular Biology.

The genes in our cells are packaged into 23 large units of DNA called chromosomes. The sex chromosomes, X and Y, differ from all other chromosomes in that they are only present as one active copy per cell instead of two. This renders a copy-number imbalance between genes located on sex chromosomes and the rest of our genome. Now researchers at Karolinska Institutet have figured out how our cells manage to double the expression of X-chromosome genes to achieve balance.

By examining gene expression dynamics in fine detail in female and male embryonic and somatic cells, the researchers found that genes on the X chromosome produced waves of gene products at a faster tempo than other chromosomes.

"The X chromosome generates 'bursts' of gene expression at higher rate that other chromosomes, pointing to the involvement of special DNA elements called enhancers in maintaining an elevated X-chromosome expression" says Bjrn Reinius, the principal investigator at the Department of Medical Biochemistry and Biophysics, who directed the study.

In female cells, carrying two X chromosomes, the increased tempo established on one X-chromosome copy during the same developmental window in which the second X-copy became inactivated. 'X inactivation' is a previously characterized mechanism that keeps one X chromosome silent in women, resulting in patches of cells expressing either the maternal or paternal copy. Male cells, carrying only one X chromosome, instead maintained a constantly fast rhythm of expression throughout developmental phases and cell types.

"Failure to establish X-chromosome dosage compensation during the early female embryogenesis is lethal and leads to early spontaneous abortion" Reinius says. "With the new knowledge, we better understand how the cells' gene expression network becomes destabilised."

According to the researchers, the findings represent a breakthrough in understanding sex-chromosome gene regulation. Understanding these chromosome-wide mechanisms could also be important in the field of regenerative medicine, since the reprogramming of cells may disturb the X-chromosome dosage balance in a gender-specific manner.

Reference: Larsson, Coucoravas, Sandberg and Reinius. 2019.X-chromosome upregulation is driven by increased burst frequency. Nature Structural and Molecular Biology. DOI: https://doi.org/10.1038/s41594-019-0306-y.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Keeping the Gene Expression of Sex Chromosomes in Balance - Technology Networks

BALTIMORE--(BUSINESS WIRE)--The Institute of Human Virology (IHV) at the University of Maryland School of Medicine commenced IHV2019 held Thursday, October 3 through Friday, October 4 at the Four Seasons Hotel in Baltimore, Maryland. This year Progress in HIV/AIDS: Challenges in 2020 opened with highlights about the recent plan for "Ending the HIV Epidemic by 2030 with expert opinions by ADM Brett Giroir, MD, Assistant Secretary for Health at the U.S. Department of Health and Human Services (HHS), Anthony Fauci, MD, Director at the National Institute of Allergy and Infectious Diseases (NIAID) and Nora Volkow, MD, Director, National Institute of Drug Abuse (NIDA), among other notable speakers. The Meeting focuses on two critical issues, including leveraging scientific advances in the field of HIV to end the epidemic in America and integrating resources to address the ongoing opioid epidemic and prevent its impact on the lives of HIV-infected patients. The Annual International Meeting attracts hundreds of elite scientists who descend upon Baltimore to share ideas and inspire medical virus research collaborations.

We have known for some time that it is, at least in theory, possible to end the HIV/AIDS epidemic, and I am pleased we are focusing on these efforts in addition to uniquely focusing on the intersection of infectious disease and opioid use disorder, said Robert C. Gallo, MD, the Homer & Martha Gudelsky Distinguished Professor in Medicine, Co-founder and Director of the Institute of Human Virology at the University of Maryland School of Medicine and Co-founder and International Scientific Advisor of the Global Virus Network (GVN). We are grateful to our nations leaders for advancing efforts to end the epidemic. Further, clinicians are uniquely positioned to advance addiction research as many infectious disease patients coming into the clinic are also afflicted with opioid use disorder.

During a gala held this evening, the 2019 IHV Lifetime Achievement Awardees, who are nominated and voted upon by IHV faculty, will be honored.

The 2019 IHV Lifetime Achievement Award for Scientific Contributions will be presented to Warner Greene, MD, PhD, Director, Gladstone Center for HIV Cure Research, Nick and Sue Hellmann Distinguished Professor of Translational Medicine, Founding and Emeritus Director, Gladstone Institute of Virology and Immunology (GIVI). Dr. Greene was a leader in the new field of the molecular biology of all human retroviruses, beginning with HTLV-1, the first discovered human retrovirus back in 1980, by Dr. Gallo and his colleagues, as well as HIV by the mid 1980s. Dr. Greenes research focused on many aspects of the understanding of the biology of the virus, including its molecular biology, its genes and their products how it replicated, how it induced, and other aspects of resistance to infection and the pathogenic mechanisms of how HIV causes disease. In recent years, he has turned his attention towards finding new ways to advance science so that a patient could live a normal life without any drug therapy whatsoever. Warner has also expanded his work to include global health activities in sub-Saharan Africa, and he has mentored more than 130 students and fellows during his career.

Warner Greene is a national treasure in the molecular biology of very important viruses and genes, said Dr. Gallo.

Two deserving individuals will receive the 2019 IHV Lifetime Achievement Award for Public Service.

The first will be presented to The Honorable Kathleen Kennedy Townsend, Director of Retirement Security, Economic Policy Institute, Lt. Governor of Maryland (1995-2003). As Marylands first woman Lt Governor, along with Gov. Parris Glendening, she recruited Dr. Gallo and his colleagues to the State. The Institute has great respect for the Lt. Governor for helping people in need and advancing human health in multiple areas, where she has worked very hard and lent her time. She became one of IHVs early board chairs, is a current IHV Board member and has been a tremendous force in paving the way for the Institutes success here in Maryland. The Lt. Governor previously served as Deputy Assistant Attorney General of the United States, led the fight to make Maryland the firstand onlystate to make service a high school graduation requirement, and has served in numerous other public service roles.

The second will be presented to The Honorable Parris Glendening, President, Smart Growth Americas Leadership Institute, President, Governors Institute on Community Design, Governor of Maryland (1995-2003). Among other important benefits from Governor Glendening, who led the recruitment of Dr. Gallo and his colleagues, Robert Redfield, MD and William Blattner, MD, to form the Institute, it was the Governors personal commitment to their mission, having shared publicly about the death of his brother from AIDS, which brought them closer. In addition, the Governor has a long history of public service, including his current national and international advocacy on smart growth, sustainability, global climate change, land conservation, transit-oriented development and equity. He was previously elected in local positions in the State and served as a professor at the University of Maryland, College Park for 27 years.

For both the Governor and Lt. Governor, we not only honor them with this Lifetime Achievement Award in Public Service because of their vital roles in the formation of the Institute, which never would have happened without them, but also as a public thank you, for their local, national and international service and leadership, said Dr. Gallo.

Since IHVs founding, the Baltimore-based Institute faculty and staff have grown from 50 to more than 300, and the Institute's patient base has grown from just 200 patients to currently more than 5,000 in Baltimore and Washington, DC, and more than 2 million in African and Caribbean nations since 2004. IHV is also internationally renowned for its basic science research, which includes a promising preventive HIV vaccine funded largely by the Bill & Melinda Gates Foundation and, in part, by others including National Institute of Allergy and Infectious Diseases.

For more information, visit http://www.ihv.org.

About the Institute of Human Virology

Formed in 1996 as a partnership between the State of Maryland, the City of Baltimore, the University System of Maryland and the University of Maryland Medical System, IHV is an institute of the University of Maryland School of Medicine and is home to some of the most globally-recognized and world-renowned experts in all of virology. The IHV combines the disciplines of basic research, epidemiology and clinical research in a concerted effort to speed the discovery of diagnostics and therapeutics for a wide variety of chronic and deadly viral and immune disorders - most notably, HIV the virus that causes AIDS. For more information, http://www.ihv.org and follow us on Twitter @IHVmaryland.

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Institute of Human Virology Hosts 21st Annual International Meeting of Top Scientists on Ending the HIV/AIDS Epidemic in America and the Intersection...

The goal of finding a cure for cancer was eclipsed long ago by the need to identify and understand the wide variety of cancers and their subtypes, and the need to focus on developing therapies specific to different cancer mechanisms and challenges. With this understanding and the rise of immunotherapy and genomic sequencing, a vast chunk of current cancer research now focuses on finding biomarkers that can predict disease response to certain drugs and guide therapy protocols.

But single biomarkers genomic, molecular, orotherwise can only go so far in predicting responses given the complexity andheterogeneity of individual malignancies and their microenvironments.

The exploding field of genomics is advancing, andresearchers are starting to examine constellations of features that may bettercharacterize disease subtypes on the path to precision medicine, but genomicsalone cannot always distinguish differing phenotypes within cancer subtypes.

Hence, the rise of radiomics and pathomics, whichare fields that take a similar approach to genomics using technology to betterunderstand features of solid tumors.

We have been moving in the latest 15 years froman organ-based cancer treatment to [a] histology-based one, to the most recentprecision medicine, which means that we are going to treat the specificalteration of the tumor independently by the site where [it] arose, Giuseppe Luigi Banna, MD, of the UnitedLincolnshire Hospital Trust in Lincoln, United Kingdom, told Cancer TherapyAdvisor.

Dr Banna and his colleagues recently published apaper exploring the promise of digital biopsy for predicting immunotherapyoutcomes based on radiomics and pathomics.1 Although moleculardeterminants such as PD-1 or PD-L1 expression, and tumor mutational burden(TMB), are already used in clinical practice, these fail in consistency,applicability, or reliability to precisely identify the responding patientsmainly because of their spatial intratumoral heterogeneity, they wrote.

Dr Banna elaborated: The following 3 mainproblems with the current assessment of PD-L1 could be overcome by pathomicsand radiomics: the different platforms used to test it, the possibleinterobserver variability, and the dynamic changes in PD-L1 expression.

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Digital Biopsies: Radiomics and Pathomics Are Important Stops on the Path to Precision Medicine - Cancer Therapy Advisor

When I imagine the inner workings of a robot, I think hard, cold mechanics running on physics: shafts, wheels, gears. Human bodies, in contrast, are more of a contained molecular soup operating on the principles of biochemistry.

Yet similar to robots, our cells are also attuned to mechanical forcesjust at a much smaller scale. Tiny pushes and pulls, for example, can urge stem cells to continue dividing, or nudge them into maturity to replace broken tissues. Chemistry isnt king when it comes to governing our bodies; physical forces are similarly powerful. The problem is how to tap into them.

In a new perspectives article in Science, Dr. Khalid Salaita and graduate student Aaron Blanchard from Emory University in Atlanta point to DNA as the solution. The team painted a futuristic picture of DNA mechanotechnology, in which we use DNA machines to control our biology. Rather than a toxic chemotherapy drip, for example, a cancer patient may one day be injected with DNA nanodevices that help their immune cells better grab ontoand snuff outcancerous ones.

For a long time, said Salaita, scientists have been good at making micro devices, hundreds of times smaller than the width of a human hair. Its been more challenging to make functional nano devices, thousands of times smaller than that. But using DNA as the component parts is making it possible to build extremely elaborate nano devices because the DNA parts self-assemble.

Just as the steam engine propelled civilization through the first industrial revolution, DNA devices may fundamentally change medicine, biological research, and the development of biomaterials, further merging man and machine.

When picturing a tiny, whirling machine surveying the body, DNA probably isnt the first candidate that comes to mind. Made up of long chains of four lettersA, T, C, and GDNA is normally secluded inside a tiny porous cage in every cell, in the shape of long chains wrapped around a protein core.

Yet several properties make DNA a fascinating substrate for making mechano-machines, the authors said. One is its predictability: like soulmates, A always binds to T, and C with G. This chemical linking in turn forms the famous double helix structure. By giving the letters little chemical additions, or swapping them out altogether with unnatural synthetic letters, scientists have been able to form entirely new DNA assemblies, folded into various 3D structures.

Rather than an unbreakable, immutable chain, DNA components are more like Japanese origami paper, or Lego blocks. While they cant make every single shapetry building a completely spherical Death Star out of Legothe chemistry is flexible enough that scientists can tweak its structure, stiffness, and coiling by shifting around the letters or replacing them with entirely new ones.

In the late fall of 1980, Dr. Nadrian Seeman was relaxing at the campus pub at New York University when he noticed a mind-bending woodcut, Depth, by MC Escher. With a spark of insight, he realized that he could form similar lattice shapes using DNA, which would make it a lot easier for him to study the molecules shape. More than a decade later, his lab engineered the first artificial 3D nanostructurea cube made out of DNA molecules. The field of DNA nanotechnology was born.

Originally considered a novelty, technologists rushed to make increasingly complex shapes, such as smiley faces, snowflakes, a tiny world map, and more recently, the worlds smallest playable tic-tac-toe set. It wasnt just fun. Along the way, scientists uncovered sophisticated principles and engineering techniques to shape DNA strands into their desired structures, forming a blueprint of DNA engineering.

Then came the DNA revolution. Reading and writing the molecule from scratch became increasingly cheaper, making it easier to experiment with brand-new designs. Additional chemical or fluorescent tags or other modifications gave scientists a direct view of their creations. Rather than a fringe academic pursuit, DNA origami became accessible to most labs, and the number of devices rapidly explodeddevices that can sense, transmit, and generate mechanical forces inside cells.

If you put together these three main components of mechanical devices, you begin to get hammers and cogs and wheels and you can start building nano machines, said Salaita.

Salaita is among several dozen labs demoing the practical uses of DNA devices.

For example, our cells are full of long-haul driver proteins that carry nutrients and other cargo throughout their interior by following specific highways (it eerily looks like a person walking down a tightrope). Just as too much traffic damages our roadways, changes in our cells logistical players can also harm the cells skeleton. Here, scientists have used DNA handles to measure force-induced changes like stretching, unfolding, and rupture of molecules involved in our cells distribution system to look for signs of trouble.

Then there are DNA tension sensors, which act like scales and other force gauges in our macroscopic world. Made up of a stretchable DNA spring to extend with force, and a fluorescent ruler that measures the extension, each sensor is anchored at one end (generally, the glass bottom of a Petri dish) and binds to a cell at the other. If the pulling force exceeds a certain threshold, the spring unfolds and quenches the fluorescent light in the ruler, giving scientists a warning that the cellular tugging is too strong.

The work may sound abstruse, but its implications are plenty. One is for CAR-T, the revolutionary cancer treatment that uses gene therapy to amp up immune cells with better graspers to target tumor cells. The kiss of death between graspers and tumors are extremely difficult to measure because its light and fleeting. Using a DNA tension sensor, the team was able to track the force during the interaction, which could help scientists engineer better CAR-T therapies. A similar construct, the DNA tension gauge tether, irreversibly ruptures under too much force. The gauge is used to track how stem cells develop into brain cells under mechanical forces, and how immune cells track down and recognize foreign invasion.

[Immune] T cells are constantly sampling cells throughout your body using these mechanical tugs. They bind and pull on proteins on a cells surface and, if the bond is strong, thats a signal that the T cell has found a foreign agent, explained Salaita. DNA devices provide an unprecedented look at these forces in the immune system, which in turn could predict how strongly the body will mount an immune response.

To the authors, however, the most promising emerging DNA devices dont just observethey can also generate forces. DNA walkers, for example, uses DNA feet to transport (and sort) molecular cargo while walking down a track also made of DNA strands. When the feet bind to the track (A to T, C to G), it releases energy that propel the walker forward.

Even more exciting are self-assembling DNA machines. The field has DNA-based devices that transmit, sense and generate mechanical forces, the authors said. But eventually, their integration will produce nanomachines that exert mechanical control over living systems.

As costs keep dropping, the authors believe well witness even more creative and sophisticated DNA nanomachines.

Several hiccups do stand in the way. Like other biomolecules, foreign DNA can be chopped up by the bodys immune system as an invader. However, the team believes that the limitation wont be a problem in the next few years as biochemistry develops chemically-modified artificial DNA letters that resist the bodys scissors.

Another problem is that the DNA devices can generate very little forceless than a billionth the weight of a paperclip, which is a little too low to efficiently control forces in our cells. The authors have a solution here too: coupling many force-generating DNA units together, or engineer translators that can turn electrical energy into mechanical forcesimilar to the way our muscles work.

Fundamentally, any advancements in DNA mechanotechnology wont just benefit medicine; they will also feed back into the design of nanomaterials. The techniques, tools and design principlesare not specific to DNA, the authors said. Add in computer-aided design templates, similar to those used in 3D printing, and potentially anyone can dream up a nano-machine design and make it a reality, said Salaita.

Image Credit: Emory University. DNA mechanotechnology expands the opportunities for research involving biomedicine and materials sciences, says Khalid Salaita, right, professor of chemistry at Emory University and co-author of the article, along with Aaron Blanchard, left, a graduate student in the Salaita Lab.

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Newswise A new study examined the effects of local anesthetics combined with standard chemotherapy for treatment of incurable triple-negative (TN) breast cancer, as well as melanoma. The results suggest that the combined treatment can lower the effective chemotherapy dosage, reduce side effects, improve tumor cell apoptosis, and reduce tumor cell migration.

Researchers at the Sbarro Health Research Organization (SHRO), at the Center for Biotechnology, Temple University, Philadelphia, and the University of L'Aquila, Italy, and the University of Siena, Italy, examined the effects of two anesthetics, ropivacaine and levobupivacaine, on two different human cancer cell lines, MDA-MB-231, triple-negative breast cancer, and A375, melanoma. This discovery may have important implications for the design of new drugs and therapeutic interventions for these recurrent and incurable tumors.

The findings were published September 20, 2019 in the Journal of Cellular Physiology.

Researchers are pursuing possible strategies for defeating TN breast cancer and melanoma by interfering with cell proliferation and apoptosis induction because these forms of cancer are notoriously difficult to treat. Building on the previously indicated effect of anesthetics in breast cancer cells and in other types of cancer in counteracting cell cycle progression, this study explores more in-depth how anesthetics may be used in cancer therapy, and the authors suggest further study is warranted.

Our studies point towards a possible way to counteract tumor growth and recurrence by interfering with cell cycle progression, apoptosis induction, and migration, says Annamaria Cimini of the University of L'Aquila, lead author of the study.

"The design of new protocols with regional anesthetics may provide new perspectives for breast and melanoma therapies reducing cancer recurrence after surgery by counteracting their metastatic potential and resistance, says Antonio Giordano, MD, PhD, founder and director of the Sbarro Institute for Cancer Research and Molecular Medicine.

About the Sbarro Health Research Organization

The Sbarro Health Research Organization (SHRO) is non-profit charity committed to funding excellence in basic genetic research to cure and diagnose cancer, cardiovascular diseases, diabetes and other chronic illnesses and to foster the training of young doctors in a spirit of professionalism and humanism. To learn more about the SHRO please visitwww.shro.org

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Treatment for Incurable Breast Cancer, Melanoma Improved by Adding Local Anesthetics - Newswise