Wistar Study Targets Telomeres To Treat Resistant Melanoma

MedicalResearch.com Interview with:
Gao Zhang, Ph.D.
Staff scientist in the Herlyn Lab
The Wistar Institute

MedicalResearch.com: What is the background for this study?

Response: The past 7 years have witnessed the great success in treating patients with unresectable or metastatic melanoma. Despite the breakthrough of molecularly targeted therapies and immune checkpoint blockade therapies, a majority of patients have experienced the rapid tumor recurrence and progression, following the dramatic regression. There is an urgent and unmet need to treat therapy-resistant tumors.

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Long Telomeres May Be Good For Heart Disease, Bad For Cancer Risk

MedicalResearch.com Interview with:

Philip C. Haycock, PhD MRC Integrative Epidemiology Unit University of Bristol Bristol, England

Dr. Philip Haycock

Philip C. Haycock, PhD
MRC Integrative Epidemiology Unit
University of Bristol
Bristol, England

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The direction and causal nature of the association of telomere length with risk of cancer and other diseases is uncertain. In a Mendelian randomization study of 83 non-communicable diseases, including 420,081 cases and 1,093,105 controls, we found that longer telomeres were associated with increased risk for several cancers but reduced risk for some other diseases, including cardiovascular diseases.

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Preventing Telomere Shortening May Delay Some Chronic Diseases and Cancer

MedicalResearch.com Interview with:

Jerry W. Shay PhD Professor Department of Cell Biology, UT Southwestern Medical Center

Dr. Jerry Shay

Jerry W. Shay PhD
Professor
Department of Cell Biology,
UT Southwestern Medical Center

MedicalResearch.com: What did you find?

Response: Telomeres are the ends of chromosomes and they gradually shortened with every cell division. There have been multiple studies proposing that shortened telomeres correlate with human aging. Most cancers overcome the shortening of telomeres and aging by activating the enzyme, telomerase. Surprisingly, the human telomerase gene (hTERT) is very close to the telomere on chromosome 5p. During human development telomerase is active until about 18 weeks of gestation. It has been a mystery until this present work of what actually causes telomerase to become silenced. We found in this current work that when telomeres are long during development the telomere loops over and helps to silence the telomerase gene. However, as we age and telomeres get progressively shorter, then telomerase becomes permissive for activation and possibly initiation of cancer. This study in part explain why most cancers are in the 65 and older segment of the population.
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Healthy Stem Cells Need Just Right Telomere Length

MedicalResearch.com Interview with:

Professor Jan Karlseder Molecular and Cell Biology Laboratory Donald and Darlene Shiley Chair Salk Institute for Biological Studies

Prof. Jan Karlseder

Professor Jan Karlseder
Molecular and Cell Biology Laboratory
Donald and Darlene Shiley Chair
Salk Institute for Biological Studies

MedicalResearch.com: What is the background for this study? 

Response: Telomeres are repetitive stretches of DNA at the ends of each chromosome whose length can be increased by an enzyme called telomerase. Our cellular machinery results in a little bit of the telomere becoming lopped off each time cells replicate their DNA and divide. As telomeres shorten over time, the chromosomes themselves become vulnerable to damage. Eventually the cells die. The exception is stem cells, which use telomerase to rebuild their telomeres, allowing them to retain their ability to divide, and to develop (“differentiate”) into virtually any cell type for the specific tissue or organ, be it skin, heart, liver or muscle—a quality known as pluripotency. These qualities make stem cells promising tools for regenerative therapies to combat age-related cellular damage and disease.

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Lab Finds Way To Lengthen Short Telomeres

Dr. John Ramunas PhD Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, CaliforniaMedicalResearch.com Interview with:
Dr. John Ramunas PhD
Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, California

Medical Research: What is the background for this study?

Dr. Ramunas: Telomeres comprise repetitive DNA sequences at the ends of chromosomes.  Telomeres protect the ends of chromosomes, but become shorter with each cell division and due to oxidative damage.  Critically short telomeres are implicated in diseases of aging and devastating genetic disorders of insufficient telomere maintenance .

Medical Research: What are the main findings?

Dr. Ramunas: Our main finding is that telomeres in human cells can be lengthened by a new method with therapeutic potential.  We delivered modified mRNA encoding TERT, the protein component of telomerase, the enzyme that increases the length of telomeres by adding DNA repeats.  The protein TERT is usually the rate limiting component of the enzyme. In this study, we used four groups of cells.  The first group received modified mRNA encoding TERT, and the other three groups were controls that received either mRNA encoding an inactive form of TERT, the solution in which TERT is delivered, or no treatment.  The telomeres of the first group (telomere extending treatment group) were extended rapidly over a period of a few days, whereas the telomeres of the three control groups were not extended.  The first group was also able to undergo more cell divisions, whereas the controls were not.  Importantly for the potential safety of our approach, the telomeres of the first group resumed shortening after they were extended.  This is important because it shows that due to the short, transient treatment, the cells were not immortalized, ie. not tumorigenic. Further, all of the cell populations treated to date eventually stopped dividing, further indicating that they were not immortalized.  We have tested the approach on cell types including fibroblasts and myoblasts and are now testing it on stem cells. A surprising and exciting finding was that we could treat the cells several times with enhanced effects on the capacity of cells to divide.  For instance, after a first treatment, we saw an increase of 50,000-fold in cell numbers before cells stopped dividing, compared to untreated cells.  If we waited a few weeks and repeated this treatment, we saw a similar gain in cell division and number.  Since the increase in numbers is compounded with each treatment, a small sample of cells, for example from a small biopsy, can be amplified to very large numbers. Continue reading

Mediterranean Diet May Delay Telomere Shortening, Increase Longevity

Immaculata De Vivo PhD Associate Professor Harvard Medical School Director, Dana Farber/Harvard Cancer Center High Throughput Genotyping Core Facility. Channing Division of Network Medicine Boston, MA 02115MedicalResearch.com Interview with:
Immaculata De Vivo PhD

Associate Professor Harvard Medical School
Director, Dana Farber/Harvard Cancer Center High Throughput Genotyping Core
Facility. Channing Division of Network Medicine
Boston, MA 02115

MedicalResearch: What is the background for this study? What are the main findings?

Dr. De Vivo: Our study found that greater adherence to the Mediterranean diet is associated with longer telomeres. Following a diet closer to the Mediterranean diet, can prevent accelerated telomere shortening. Our unique contribution to the literature is that we provide a potential molecular mechanism, preventing telomere shortening. Telomeres are bits of DNA that protect your chromosomes.

MedicalResearch: Is telomere shortening reversible?

Dr. De Vivo: Telomere shortening is a biological process, the shorten with age.

However, lifestyle choices can help to prevent accelerated shortening.

Fruits, vegetables, olive oil and nuts – key components of the Mediterranean diet have well known antioxidant and anti-inflammatory effects that could balance out the “bad effects” of smoking and obesity.

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Mindfulness Meditation Improved Telomere Length in Breast Cancer Patients

Linda E. Carlson, Ph.D., R.Psych.                Enbridge Research Chair in Psychosocial Oncology Alberta Innovates-Health Solutions Health Scholar Professor, Department of Oncology, Faculty of Medicine    Adjunct Professor, Department of Psychology, Faculty of Arts University of Calgary Clinical Psychologist, Director of Research Department of Psychosocial ResourcesMedicalResearch.com Interview with:
Linda E. Carlson, Ph.D., R.Psych.               
Enbridge Research Chair in Psychosocial Oncology
Alberta Innovates-Health Solutions Health Scholar
Professor, Department of Oncology, Faculty of Medicine
Adjunct Professor, Department of Psychology, Faculty of Arts
University of Calgary Clinical Psychologist, Director of Research
Department of Psychosocial Resources

Medical Research: What is the background for this study? What are the main findings?

Dr. Carlson: We have been investigating the effects of cancer support programs including the two in this study, Mindfulness-based cancer recovery, an 8-week group program in which patients learn mindfulness meditation and gentle yoga, and supportive-expressive therapy, a 12-week program where patients share difficult emotions in a supportive group environment. We know there is psychological benefit of these programs, but what about effects in the body?

Telomeres are the protective caps on the end of chromosomes (like the tips on shoelaces) that protect them from damage and degredation. They are longest when we are young and naturally get shorter as we age. Shorter telomere’s are associated with higher risk for many diseases, including cancer, and people with higher stress levels tend to have shorter telomeres.

This is the first study to investigate whether short psychosocial interventions can affect telomere length in cancer pateints. We randomly assigned breast cancer survivors with cancer-related distress, feelings such as anxiety, fear, worry, and depression, to either mindfulness-based cancer recovery, supportive expressive therapy or a control group that just had a minimal intervention. We took blood samples before and after the groups (or at equal time points for those in the control condition) and measured the length of the telomeres.

Women in both of the active support groups maintained the length of their telomeres over time, but the telomere length of women in the control group became shorter. This is the first controlled study to show that short-term interventions can actually have some effect on cellular aging in the telomeres.
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Shorter Telomeres Associated With Risk of Coronary Heart Disease

MedicalResearch.com Interview with:
Philip Haycock, PhD
Post-Doctoral Research Assistant
MRC Integrative Epidemiology Unit
University of Bristol
Bristol, BS8 2BN, UK

Medical Research: What are the main findings of the study?

Dr. Haycock: We found that shorter telomeres were significantly associated with risk of coronary heart disease and that the association was independent of conventional vascular risk factors, including age, sex, body mass index, smoking, history of diabetes, blood pressure and lipid markers.

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