Category Archives: Gene Medicine

MSUToday

Research offers new clues to rare genetic disease MSUToday Tuberous sclerosis complex, or TSC, is considered a rare genetic disease, yet for the estimated 50,000 patients in the United States and almost 2 million individuals worldwide, dealing with its symptoms can be overwhelming. It's a devastating disease ...

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Research offers new clues to rare genetic disease - MSUToday

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Sea anemone genes could spur advancements in regenerative medicine - Digital Trends

TissueGene has been awarded a $750,000 clinical grant from the Maryland Technology Development Corporation (TEDCO) via the MSCRF. The clinical grant is to be used for conducting clinical trials in Maryland using cell therapy. This money is part of Accelerating Cure, a new TEDCO initiative to support regenerative medicine and cell therapy technologies in Maryland.

The grant award will be used by TissueGene to fund a component of a clinical study at a Maryland location for its US Phase III clinical trial for Invossa. The ultimate outcome of this study is the verification that Invossa exerts its therapeutic effect not only by tissue regeneration but on other inflammatory aspects of the disease such as synovitis.

The title of the grant is "Assessment of the Efficacy of TG-C in Treating Synovitis Using Contrast Enhanced MRI in a Clinical Study of Knee Osteoarthritis." The Principal Investigator (PI) for the study will be Dr. Gurdyal Kalsi, Chief Medical Officer of TissueGene.

"We are excited to support this important clinical trial and the growth of TissueGene in Maryland," said Dr. Dan Gincel, TEDCO's VP University Partnerships, and MSCRF's Executive Director. "We look forward to see many more patients treated and cured from this and other devastating diseases."

Woosok Lee, CEO of TissueGene stated, "As a Maryland-based company, TissueGene is honored by the grant award from the State of Maryland which has consistently demonstrated its commitment to supporting innovative therapies such as Invossa, which could potentially be the world's first disease-modifying drug for treating osteoarthritis."

Invossa is a first-in-class osteoarthritis drug designed to conveniently and effectively treat osteoarthritis of the knee through a single intra-articular injection. Clinical trials completed in Korea and on-going trials in the US have demonstrated pain relief, increased mobility, and improvements in joint structure offering substantial convenience for the nearly 33 million Americans with osteoarthritis who would otherwise be in need of surgery.

TissueGene, Inc. TissueGene, Inc., is a Maryland-based regenerative medicine company specializing in cell and gene therapy. TissueGene's lead product is Invossa, an allogeneic, cell and gene therapy for osteoarthritis of the knee that has completed Phase II clinical trials in the US. TissueGene has recently reached an agreement with the U.S. Food and Drug Administration regarding a Special Protocol Assessment (SPA) for a Phase 3 clinical trial for Invossa. Information can be found at the NIH registry, ww.clinicaltrials.gov. For additional information about TissueGene, Inc., please visit http://www.tissuegene.com.

The Maryland Stem Cell Research Fund (MSCRF) was established by the State of Maryland under the Maryland Stem Cell Research Act of 2006 to promote State-funded stem cell research and cures through grants and loans to public and private entities in the State. Administered by The Maryland Technology Development Corporation (TEDCO), the MSCRF is overseen by an independent Commission that sets policy and develops criteria, standards and requirements for applications to the Fund. For more information about the Maryland Stem Cell Research Fund, please visit http://www.mscrf.org.

The Maryland Technology Development Corporation (TEDCO) is the go-to source for entrepreneurial support and guidance for technology start-ups and early-stage companies engaged in bringing innovative ideas to market. For over nineteen years, the organization has provided funding, mentoring and networking opportunities to support Maryland's innovation ecosystem. It is frequently ranked as one of the most active seed/early-stage investors in the nation. The organization plays a key role in bringing research created in Maryland's educational institutions and federal laboratories into the commercial marketplace. For more information on TEDCO and its programs and resources, visit http://www.TEDCO.md.

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/tissuegene-awarded-750000-maryland-stem-cell-grant-for-invossa-clinical-study-300482506.html

SOURCE TissueGene, Inc.

http://www.tissuegene.com

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TissueGene Awarded $750000 Maryland Stem Cell Grant for Invossa Clinical Study - PR Newswire (press release)

NBCNews.com

Gene Testing for Most Effective Drugs Could Help Save Lives NBCNews.com Gene Testing for Most Effective Drugs Could Help Save Lives. Thu, Jun 29. An apparent breakthrough in the field of personalized medicine: people can now test their genetic profiles to see how they might process a variety of drugs from pain relievers to ... and more »

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Gene Testing for Most Effective Drugs Could Help Save Lives - NBCNews.com

Gene Medicine TherapyMarketanalysis is provided for global market including development trends by regions, competitive analysis of Gene Medicine Therapymarket. The Gene Medicine Therapyindustry report firstly announced the Gene Medicine TherapyMarket fundamentals: definitions, classifications, applications and market overview; product specifications; manufacturing processes; cost structures, raw materials and so on.

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Table of Contents:

Chapter 1: Gene Medicine TherapyMarket Overview

1.1 Definition

1.2 Classification Analysis

1.3 Application Analysis

1.4 Gene Medicine TherapyIndustry Chain Structure Analysis

1.5 Gene Medicine TherapyMarket Development Overview

1.6 Global Gene Medicine TherapyMarket Comparison Analysis

1.6.1 Global Import Market Analysis

1.6.2 Global Export Market Analysis

1.6.3 Global Main Region Market Analysis

1.6.4 Global Market Comparison Analysis

1.6.5 Global Market Development Trend Analysis

Chapter 2:Gene Medicine TherapyUp and Down Stream Industry Analysis

2.1 Upstream Raw Materials Analysis of Gene Medicine TherapyMarket

2.1.1 Upstream Raw Materials Price Analysis

2.1.2 Upstream Raw Materials Market analysis

2.1.3 Upstream Raw Materials Market Trends

2.2 Down Stream Market Analysis of Gene Medicine TherapyMarket

2.1.1 Down Stream Market Analysis

2.2.2 Down Stream Demand Analysis

2.2.3 Down Stream Market Trend Analysis

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Chapter 3: Gene Medicine TherapyProductions Supply Sales Demand Market Status and Forecast

3.1 2012-2017 Gene Medicine TherapyMarket Capacity Production Overview

3.2 2012-2017 Gene Medicine TherapyProduction Market Share Analysis

3.3 2012-2017 Gene Medicine TherapyMarket Demand Overview

3.4 2012-2017 Supply Demand and Shortage of Gene Medicine TherapyIndustry

3.5 2012-2017 Gene Medicine TherapyImport Export Consumption

3.6 2012-2017 Gene Medicine TherapyCost Price Production Value Gross Margin

In the end Gene Medicine TherapyMarket report provides the main region, market conditions with the product price, profit, capacity, production, supply, demand and market growth rateand forecast etc. Gene Medicine TherapyMarket report also Present new project SWOT analysis, investment feasibility analysis, and investment return analysis.

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Gene Medicine Therapy Market Growth Analysis, Share, Demand by Regions, Types and Analysis of Key Players ... - MilTech

Marco Solmi,1,2 Andrea Murru,3 Isabella Pacchiarotti,3 Juan Undurraga,4,5 Nicola Veronese,2,6 Michele Fornaro,7,8 Brendon Stubbs,2,911 Francesco Monaco,2 Eduard Vieta,3 Mary V Seeman,12 Christoph U Correll,13,14 Andr F Carvalho2,15

1Neuroscience Department, University of Padua, 2Institute for Clinical Research and Education in Medicine, Padua, Italy; 3Bipolar Disorders Unit, Institute of Neuroscience, Hospital Clnic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; 4Department of Psychiatry, Faculty of Medicine, Clnica Alemana Universidad del Desarrollo, 5Early Intervention Program, J. Horwitz Psychiatric Institute, Santiago, Chile; 6National Research Council, Ageing Section, Padua, 7Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, School of Medicine, University Federico II, Naples, Italy; 8New York State Psychiatric Institute, Columbia University, New York, NY, USA; 9Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, 10Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, 11Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK; 12Institute of Medical Science, Toronto, ON, Canada; 13Department of Psychiatry Research, Zucker Hillside Hospital, Northwell Health, Glen Oaks, 14Department of Psychiatry and Molecular Medicine Hempstead, Hofstra Northwell School of Medicine, Hempstead, NY, USA; 15Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Cear, Fortaleza, Cear, Brazil

Abstract: Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole,ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the behavioral toxicity conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed first. However, alongside with safety, efficacy should also be considered on a patient-tailored basis. Keywords: antipsychotics, side effects, tolerability, safety, psychosis, psychiatry

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art ... - Dove Medical Press

Patients who underwent genetic screenings now fear that documentation of the results in their medical records could lead to problems if a new health law is enacted. Sam Edwards/Caiaimage/Getty Images hide caption

Patients who underwent genetic screenings now fear that documentation of the results in their medical records could lead to problems if a new health law is enacted.

Two years ago, Cheasanee Huette, a 20-year-old college student in Northern California, decided to find out if she was a carrier of the genetic mutation that gave rise to a disease that killed her mother. She took comfort in knowing that whatever the result, she'd be protected by the Affordable Care Act's guarantees of insurance coverage for pre-existing conditions.

Her results came back positive. Like her mother, she's a carrier of one of the mutations known as Lynch syndrome. The term refers to a cluster of mutations that can boost the risk of a wide range of cancers, particularly colon and rectal.

As Republican lawmakers advance proposals to overhaul the ACA's consumer protections, Huette frets that her future health coverage and employment options will be defined by that test.

She even wonders if documentation of the mutation in her medical records and related screenings could rule out individual insurance plans. She's currently covered under her father's policy. "Once I move to my own health care plan, I'm concerned about who is going to be willing to cover me, and how much will that cost," she says.

In recent years, doctors have urged patients to be screened for a variety of diseases and predisposition to illness, confident it would not affect their future insurability. Being predisposed to an illness such as carrying the BRCA gene mutations associated with breast and ovarian cancer does not mean a patient will come down with the illness. But knowing they could be at risk may allow patients to take steps to prevent its development.

Under the current health law, many screening tests for widespread conditions such as prediabetes are covered in full by insurance. The Centers for Disease Control and Prevention and the American Medical Association have urged primary care doctors to test patients at risk for prediabetes. But doctors, genetic counselors and patient advocacy groups now worry that people will shy away from testing as the ACA's future becomes more uncertain.

Dr. Kenneth Lin, a family physician at Georgetown University School of Medicine in Washington, D.C., says if the changes proposed by the GOP become law, "you can bet that I'll be even more reluctant to test patients or record the diagnosis of prediabetes in their charts." He thinks such a notation could mean hundreds of dollars a month more in premiums for individuals in some states under the new bill.

Huette says she's sharing her story publicly since her genetic mutation is already on her medical record.

But elsewhere, there have been "panicked expressions of concern," says Lisa Schlager of the patient advocacy group Facing Our Risk of Cancer Empowered (FORCE). "Somebody who had cancer even saying, 'I don't want my daughter to test now.' Or 'I'm going to be dropped from my insurance because I have the BRCA mutation.' There's a lot of fear."

Those fears, which come in an era of accelerating genetics-driven medicine, rest upon whether a gap that was closed by the ACA will be reopened. That remains unclear.

A law passed in 2008, the Genetic Information Nondiscrimination Act, bans health insurance discrimination if someone tests positive for a mutation. But that protection stops once the mutation causes "manifest disease" essentially, a diagnosable health condition.

That means "when you become symptomatic," although it's not clear how severe the symptoms must be to constitute having the disease, says Mark Rothstein, an attorney and bioethicist at the University of Louisville School of Medicine in Kentucky, who has written extensively about GINA.

The ACA, passed two years after GINA, closed that gap by barring health insurance discrimination based on pre-existing conditions, Rothstein says.

On paper, the legislation unveiled by Senate Majority Leader Mitch McConnell last week wouldn't let insurers set higher rates for people with pre-existing conditions, but it could effectively exclude such patients from coverage by allowing states to offer insurance plans that don't cover certain maladies, health analysts say. Meanwhile, the bill that passed the House last month does have a provision that allows states to waive protections for people with pre-existing conditions, if they have a gap in coverage of 63 days or longer in the prior year.

When members of a Lynch Syndrome social media group were asked for their views on genetic testing amid the current health care debate, about two dozen men and women responded. Nearly all said they were delaying action for themselves or suggesting that family members, particularly children, hold off.

Huette was the only one who agreed to speak for attribution. She says before the ACA was enacted, she witnessed the impact that fears about insurance coverage had on patients. Her mother, a veterinarian, had wanted to run her own practice but instead took a federal government job for the guarantee of health insurance. She died at the age of 57 of pancreatic cancer, one of six malignancies she had been diagnosed with over the years.

Huette says she doesn't regret getting tested. Without the result, Huette points out, how would she have persuaded a doctor to give her a colonoscopy in her 20s?

"Ultimately, my health is more important than my bank account," she says.

Kaiser Health News, a nonprofit health newsroom whose stories appear in news outlets nationwide, is an editorially independent part of the Kaiser Family Foundation.

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Researchers in China have discovered another gene that confers resistance to the last-resort antibiotic colistin.

In a study yesterday in mBio, the researchers report that the MCR-3 gene was discovered in a fecal sample obtained from an apparently healthy pig at a farm in Shangdong province during a routine surveillance study of antimicrobial resistant bacteria. The gene was located on a colistin-resistant Escherichia coli isolate, on a plasmid that contained 18 additional antibiotic resistance genes.

The authors of the study say they're concerned the gene may already be widely disseminated, and that scientists should be on the lookout for it. "Screening for the mcr-3 gene should be urgently included in the surveillance of colistin-resistant Gram-negative pathogens from animals, humans, and the environment," they write.

The discovery was made by several members of the research team that first reported the discovery of the mobile colistin resistance gene MCR-1 in E coli from pigs, pork products, and humans in China in November 2015. That finding raised international concern, given that colistin is an antibiotic of last resort for multidrug-resistant bacterial infections. The gene's location on plasmids, which are highly mobile pieces of DNA that can be shared within and between different bacterial species, means that resistance to colistin can quickly spread.

Since then, MCR-1 has been identified in bacteria from humans, animals, and the environment in more than 30 countries, including the United States, and studies have documented the spread of the gene to the clinical setting in China. Earlier this year, Chinese scientists reported an outbreak of MCR-1carrying Klebsiella pneumoniae among patients in a pediatric leukemia ward.

In addition, six different variants of the MCR-1 gene have been reported, along with a second mobile resistance gene, MCR-2.

In yesterday's study, the researchers report that MCR-3 was identified when molecular testing showed the colistin-resistant E coli isolate was negative for both MCR-1 and MCR-2, but contained an unknown colistin resistance gene that could be transferred to another E coli strain. Further analysis revealed that the gene was located on a plasmid similar to MCR-1carrying plasmids.

The investigators also found that the genomic sequence of MCR-3 closely resembled sequences found in Enterobacteriaceae and Aeromonas bacteria collected from both clinical infection and environmental samples in 12 countries on four continents, a finding that suggests the previously unidentified gene may already have spread. "Due to the ubiquitous profile of aeromonads in the environment and the potential transfer of mcr-3 between Enterobacteriaceae and Aeromonas species, the wide spread of mcr-3 may be largely underestimated," they write.

Up until recently, colistin was widely used in Chinese agriculture, and MCR-1 is thought to be a product of selection pressure caused by that use. China banned use of the drug in animal feed in 2016, based in part on the discovery of MCR-1.

Because of its toxicity, colistin was rarely used in human medicine until the late 1990s, when resistance to other last-resort drugs, including carbapenems, necessitated its use in serious multidrug-resistant infections. Colistin is on the World Health Organization's list of critical antimicrobials for human medicine.

One of the major concerns about MCR-1 and its offshoots is that it's often located on plasmids that contain other antibiotic resistance genes. That raises the possibility of bacterial infections that will not respond to any antibiotic. The authors say continuous monitoring for mobile resistance elements in colistin-resistant bacteria is "imperative for understanding and tackling the dissemination of mcr genes in both the agricultural and health care sectors."

Scientists with the SENTRY Antimicrobial Surveillance Program, which monitors worldwide pathogens and changes in antibiotic resistance patterns, have been tracking the global spread of MCR-1 since it was identified, while the Centers for Disease Control and Prevention has been hunting for the gene in the United States.

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Jun 27 mBio study

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New colistin resistance gene identified in China - CIDRAP

June 28, 2017 Disruption of a region in chromosome 6 or epigenetic modifications of the DNA block Sestrin1 expression and these contribute to the development of follicular lymphoma. Credit: Elisa Oricchio/Natalya Katanayeva/EPFL

Follicular lymphoma is an incurable cancer that affects over 200,000 people worldwide every year. A form of non-Hodgkin lymphoma, follicular lymphoma develops when the body starts making abnormal B-cells, which are white blood cells that in normal conditions fight infections. This cancer is associated with several alterations of the cell's DNA, but it has been unclear which gene or genes are involved in its development. EPFL scientists have now analyzed the genomes of more than 200 patients with follicular lymphoma, and they discover that a gene, Sestrin1, is frequently missing or malfunctioning in FL patients. The discovery opens to new treatment options and it is now published in Science Translational Medicine.

One of the common features of follicular lymphoma is a genetic abnormality between two chromosomes (14 and 18). In an event known as "chromosomal translocation" the two chromosomes "swap" certain parts with each other. This triggers the activation of a gene that protects cells from dying, making cells virtually immortalthe hallmark of a tumor.

Moreover, approximately 30% of follicular lymphoma patients lose also a portion of chromosome 6, affecting multiple genes involved in suppressing the emergence of a tumor. These patients typically have poor prognosis. Another 20 % of patients have alterations causing chromosomal disorganization and the consequent malfunctioning of several genes and proteins. The bottom line is that for both group of patients it is very difficult to pinpoint which of all the affected genes are actually causing the disease.

The lab of Elisa Oricchio at EPFL, with colleagues from the US and Canada, analyzed the genomes of over 200 follicular lymphoma patients. Their analyses revealed that a specific gene, Sestrin1, can be harmed by both loss of chromosome 6 and silenced in patients.

Sestrin1 helps the cell defending itself against DNA damagefor example after exposure to radiationand oxidative stress. In fact, Sestrin1 is part of the cell's anti-tumor mechanism that stops potentially cancerous cells from growing.

Disruption of a region in chromosome 6 or epigenetic modifications of the DNA block Sestrin1 expression and these contribute to the development of Follicular Lymphoma.

Beyond identifying the Sestrin1 gene as frequently altered in FL patients, the scientists demonstrated that Sestrin1 is able to suppress tumors in vivo. They showed that Sestrin1 exerts its anti-tumor effects by blocking the activity of a protein complex called mTORC1, which is well known for controlling protein synthesis as well as acting as a sensor for nutrient or energy changes in the cell.

Finally, the identification of loss of Sestrin1 as a key event behind the development of follicular lymphoma is particular important because it helps identifying patients that will benefit from new therapies. Indeed, this study shows that the therapeutic efficacy of a new drug that is currently in clinical trial depends on Sestrin1. Importantly, this dependency can be extended beyond follicular lymphoma to other tumor types.

Explore further: Combination therapy may help patients with follicular lymphoma

More information: E. Oricchio el al., "Genetic and epigenetic inactivation of SESTRIN1 controls mTORC1 and response to EZH2 inhibition in follicular lymphoma," Science Translational Medicine (2017). stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aak9969

A new study in The Journal of Experimental Medicine reveals that a high-risk group of patients with follicular lymphoma could benefit from a novel drug combination.

Mutations present in a blood cancer known as follicular lymphoma have revealed new molecular targets for potential treatments, according to researchers at Queen Mary University of London (QMUL) together with collaborators ...

Immune cellular therapy is a promising new area of cancer treatment. Anti-cancer therapeutics, such as chimeric antigen receptor (CAR) modified T cells, can be engineered to target tumor-associated antigens to attack and ...

Follicular lymphoma (FL), the second most common form of non-Hodgkin lymphoma, is a largely incurable disease of B cells, yet in many cases, because of its indolent nature, survival can extend to well beyond 10 years following ...

The goal for many cancer patients is to reach the five-year, disease-free mark, but new research from UR Medicine's Wilmot Cancer Institute suggests that two years might be a more practical survival goal for people with follicular ...

(HealthDay)An initial watch-and-wait strategy does not have a detrimental effect on the freedom from treatment failure (FFTF) or overall survival rate in selected patients with low-tumor burden follicular lymphoma compared ...

While mutations in protein-coding genes have held the limelight in cancer genomics, those in the noncoding genome (home to the regulatory elements that control gene activity) may also have powerful roles in driving tumor ...

Scientists have had limited success at identifying specific inherited genes associated with prostate cancer, despite the fact that it is one of the most common non-skin cancers among men. Researchers at University of Utah ...

Cancerous tumors are formidable enemies, recruiting blood vessels to aid their voracious growth, damaging nearby tissues, and deploying numerous strategies to evade the body's defense systems. But even more malicious are ...

Follicular lymphoma is an incurable cancer that affects over 200,000 people worldwide every year. A form of non-Hodgkin lymphoma, follicular lymphoma develops when the body starts making abnormal B-cells, which are white ...

Leukemia researchers led by Dr. John Dick have traced the origins of relapse in acute myeloid leukemia (AML) to rare therapy-resistant leukemia stem cells that are already present at diagnosis and before chemotherapy begins.

Adding an investigational antibody to the chemotherapy rituximab appears to restore its cancer-killing properties in certain leukemia patients with a natural resistance to the drug, according to a small, proof-of-concept ...

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The gene behind follicular lymphoma - Medical Xpress

June 29, 2017 Micrograph showing prostatic acinar adenocarcinoma (the most common form of prostate cancer) Credit: Wikipedia

Scientists have had limited success at identifying specific inherited genes associated with prostate cancer, despite the fact that it is one of the most common non-skin cancers among men. Researchers at University of Utah Health studied prostate cancer patients with multiple cancer diagnoses, many who would not be recommended for genetic tests following current guidelines, to identify genetic mutations that may influence cancer treatment and cancer risk assessment for family members. Their findings are reported in the June issue of the journal Cancer.

"We commonly use a combination of a patient's personal and family cancer histories to identify those individuals who may have a mutation in a gene that predisposes that individual to developing cancers," said Patrick Pili, M.D., medical oncology fellow at the University of Texas MD Anderson Cancer Center. "Testing for hereditary cancers impacts not only the patient with cancer but also potentially the cancer screening and health outcomes of their entire family, but many prostate cancer patients do not meet the current guidelines to test for genetic cancer heritability."

Pili was part of a research team led by Kathleen Cooney, M.D., chair of the Department of Internal Medicine at U of U Health and a Huntsman Cancer Institute investigator, who proposed a strategy to identify germline mutations in men selected for the study based on their clinical history not their family history.

The study was highly selective, including 102 patients who had been diagnosed with prostate cancer and at least one additional primary cancer, like melanoma, pancreatic cancer, testicular cancer, or Hodgkin lymphoma.

The researchers examined the frequency of harmful germline mutations in this group of men. These mutations originate on either the egg or sperm and become incorporated into the DNA of every cell in the body of the resulting offspring.

Using next generation sequencing, the researchers found that 11 percent of the patients had a disease-causing mutation in at least one cancer-predisposing gene, which suggests these genetic variations contributed to their prostate cancer. Cooney found no difference in cancer aggressiveness or age of diagnosis compared to patients without these mutations.

In addition, a certified genetic counselor and co-investigator Elena Stoffel, M.D., University of Michigan Comprehensive Cancer Center, reviewed personal and family histories from each patient to determine whether they would meet clinical genetic testing guidelines. The majority of the men in the study, 64 percent, did not meet current criteria to test for hereditary cancer based on personal and/or family history.

The findings suggest that there are men with heritable prostate cancer-predisposing mutations that are not eligible for genetic screening under current guidelines.

"This is the first paper in which we can show the potential of using a clinical history of multiple cancers, including prostate cancer, in a single individual to identify inherited germline mutations," Cooney said.

The majority of harmful mutations identified were in genes involved in DNA repair.

"These mutations prevent the DNA from healing itself, which can lead to a predisposition for cancer," Cooney said.

This result is also beneficial because drugs like PARP [poly ADP ribose polymerase] inhibitors have a better success rate in treating cancers with the underlying gene mutation associated with DNA repair.

Cooney cautions that this is a small pilot study rather than a broader epidemiological survey, and it consists of a highly specific subset of patients.

"We cannot generalize these findings to the broader population, because we used highly selective criteria to tip us off to patients that may have mutations outside typical hereditary genetic patterns," she said.

The 102 patients included in the study were identified from the University of Michigan's Prostate Cancer Genetics Project, which registers patients who are diagnosed with prostate cancer before age 55 or who have a first- or second-degree relative with prostate cancer. In addition, the research team identified patients from the University of Michigan's Cancer Genetics Registry, which includes individuals with personal or family history suggestive of a hereditary risk of cancer.

"Our findings are in line with those of other studies, suggesting that approximately 1 in 10 men with advanced prostate cancer harbors a genetic variant associated with increased cancer risk," said Stoffel. "While family history is an important tool, there may be better ways to identify patients with genetic risk."

Future studies with larger sample sizes will include sequencing of tumors that will allow investigators to more carefully explore the different features associated with tumors that arise in individuals with germline mutations.

"This approach will help us identify patients at greater risk for aggressive prostate cancer so they can seek earlier screening while pre-symptomatic," Cooney said.

Explore further: Are men with a family history of prostate cancer eligible for active surveillance?

More information: Patrick G. Pili et al. Germline genetic variants in men with prostate cancer and one or more additional cancers, Cancer (2017). DOI: 10.1002/cncr.30817

Journal reference: Cancer

Provided by: University of Utah

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Researchers propose new approach to identify genetic mutations in men with prostate cancer - Medical Xpress