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Oncotarget published this trending review on March 30, 2017, entitled, "Physical activity and telomere length: Impact of aging and potential mechanisms of action" by researchers from the Department of Nursing, College of Nursing and Health Sciences, University of Massachusetts Boston, Boston, MA; Department of Exercise and Health Sciences, College of Nursing and Health Sciences, University of Massachusetts Boston, Boston, MA;  Department of Kinesiology & Sport Management, Texas Tech University, Lubbock, TX; Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, Columbus, OH.

DOI - https://doi.org/10.18632/oncotarget.16726

Correspondence to - Tongjian You - tongjian.you@umb.edu and Li Zuo - zuo.4@osu.edu

Abstract:
Telomeres protect the integrity of information-carrying DNA by serving as caps on the terminal portions of chromosomes. Telomere length decreases with aging, and this contributes to cell senescence. Recent evidence supports that telomere length of leukocytes and skeletal muscle cells may be positively associated with healthy living and inversely correlated with the risk of several age-related diseases, including cancer, cardiovascular disease, obesity, diabetes, chronic pain, and stress. In observational studies, higher levels of physical activity or exercise are related to longer telomere lengths in various populations, and athletes tend to have longer telomere lengths than non-athletes. This relationship is particularly evident in older individuals, suggesting a role of physical activity in combating the typical age-induced decrements in telomere length. To date, a small number of exercise interventions have been executed to examine the potential influence of chronic exercise on telomere length, but these studies have not fully established such relationship. Several potential mechanisms through which physical activity or exercise could affect telomere length are discussed, including changes in telomerase activity, oxidative stress, inflammation, and decreased skeletal muscle satellite cell content. Future research is needed to mechanistically examine the effects of various modalities of exercise on telomere length in middle-aged and older adults, as well as in specific clinical populations.

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Keywords - telomere length, leukocyte, muscle, physical activity, exercise

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Trending With Impact: Physical Activity, Telomere Length and Aging

Dr. Sandip Pravin Patel, Dr. Karen Yun and Dr. Karen Mccowen from the University of California San Diego, discuss a research paper they co-authored that was published by Oncotarget in Volume 11, Issue 28, entitled, “Rapid onset type 1 diabetes with anti-PD-1 directed therapy.”

DOI - https://doi.org/10.18632/oncotarget.27665

Correspondence to - Sandip Pravin Patel - patel@ucsd.edu

Abstract
Type 1 diabetes is a rare immune-related adverse event (irAE) caused by checkpoint inhibitors with serious risk for diabetic ketoacidosis (DKA). Using our electronic medical record, we identified 1327 adult patients who received PD-(L)1 or CTLA-4 inhibitors from 2013 to 2018. Of the patients who received immunotherapy, 5 (0.38%) patients were found to have type 1 diabetes, all of whom presented with DKA requiring insulin at 20 to 972 days from their first anti-PD-(L)1 dose. All patients were treated with anti-PD-1 therapy (nivolumab or pembrolizumab). Four patients had new onset diabetes with mean HbA1c of 9.1% on DKA presentation and persistent elevations over time. Two patients who tested positive for glutamic acid decarboxylase (GAD) antibodies presented with DKA at 20 and 106 days from first anti-PD-1 administration whereas patients who were autoantibody negative had DKA more than a year later. Type 1 diabetes occurs within a wide time frame after anti-PD-1 initiation and commences with an abrupt course. Our case series suggests that monitoring glycemia in patients on PD-1 inhibitors is not predictive for diabetes occurrence. GAD autoantibodies could portend earlier onset for diabetes, although further prospective studies are needed to elucidate their diagnostic utility and contribution in therapeutic interception.

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Press release - https://www.oncotarget.com/index.php?journal=oncotarget&page=news&op=press&item=oncotarget-rapid-onset-type-1-diabetes-with-anti-pd-1-directed-therap

Keywords - type 1 diabetes, diabetic ketoacidosis (DKA), immune-related adverse event (irAE), immunotherapy, PD-1 inhibitors

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Author Insight: Rare Incidence of Type 1 Diabetes Induced by Immunotherapy

Dr. Sridhar Mani from Medicine and Genetics of The Albert Einstein College of Medicine, Bronx, NY, details his editorial published by Oncotarget in Volume 11, Issue 19, entitled, “Microbial metabolite mimicry: one step closer to drug discovery.”

DOI - https://doi.org/10.18632/oncotarget.27591

Correspondence to - Sridhar Mani - sridhar.mani@einsteinmed.org

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Keywords - microbial metabolites, inflammation, IBD, mimicry, drugs

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Author Insight: Microbial Metabolite Mimicry May Improve Drug Discovery

Oncotarget published this trending research paper chosen as the cover for Volume 12, Issue 6, entitled, "Genomic and neoantigen evolution from primary tumor to first metastases in head and neck squamous cell carcinoma," by researchers from the Division of Medical Oncology, Washington University in St. Louis, St. Louis, MO; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO; Department of Pathology and Cell Biology, Columbia University, New York, NY; Division of Hematology/Oncology, Columbia University, New York, NY; Department of Genetics, Washington University in St. Louis, St. Louis, MO; Division of Pediatric Hematology and Oncology, St. Louis Children’s Hospital, St. Louis, MO; Siteman Cancer Center, St. Louis, MO.

Abstract:
Head and neck cell squamous-cell carcinomas (HNSCC) are a group of common cancers typically associated with tobacco use and human papilloma virus infection. Up to half of all cases will suffer a recurrence after primary treatment. As such, new therapies are needed, including therapies which promote the anti-tumor immune response. Prior work has characterized changes in the mutation burden between primary and recurrent tumors; however, little work has characterized the changes in neoantigen evolution. We characterized genomic and neoantigen changes between 23 paired primary and recurrent HNSCC tumors. Twenty-three biopsies from patients originally diagnosed with locally advanced disease were identified from the Washington University tumor bank. Whole exosome sequencing, RNA-seq, and immunohistochemistry was performed on the primary and recurrent tumors. Within these tumors, we identified 6 genes which have predicted neoantigens in 4 or more patients. Interestingly, patients with neoantigens in these shared genes had increased CD3+ CD8+ T cell infiltration and duration of survival with disease. Within HNSCC tumors examined here, there are neoantigens in shared genes by a subset of patients. The presence of neoantigens in these shared genes may promote an anti-tumor immune response which controls tumor progression.

Press release - https://www.oncotarget.com/news/pr/genomic-and-neoantigen-evolution-in-head-and-neck-squamous-cell-carcinoma/

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DOI - https://doi.org/10.18632/oncotarget.27907

Full text - https://www.oncotarget.com/article/27907/text/

Correspondence to - Brian A. Van Tine - bvantine@wustl.edu

Keywords - head and neck squamous cell carcinoma, neoantigens, mutational evolution, tumor relapse, immune cell infiltration

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Paper Spotlight: Genomic and Neoantigen Evolution in Head, Neck Cancer

Oncotarget published this trending research perspective in Volume 12, Issue 25, entitled, "Cell fusion as a link between the SARS-CoV-2 spike protein, COVID-19 complications, and vaccine side effects" by Yuri Lazebnik, PhD., from Lerna Consulting, New Haven, CT.

Abstract:
A distinctive feature of the SARS-CoV-2 spike protein is its ability to efficiently fuse cells, thus producing syncytia found in COVID-19 patients. This commentary proposes how this ability enables spike to cause COVID-19 complications as well as side effects of COVID-19 vaccines, and suggests how these effects can be prevented.

Press release - https://www.oncotarget.com/news/pr/sars-cov-2-covid-19-vaccine-side-effects/

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DOI - https://doi.org/10.18632/oncotarget.28088

Full text - https://www.oncotarget.com/article/28088/text/

Correspondence to - Yuri Lazebnik - yuri@lernaconsulting.com

Keywords - cell fusion, thrombosis, neuropathy, cancer, vaccines

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Trending With Impact: Negative Effects of the Spike Protein in SARS-CoV-2 and Some Vaccines

Oncotarget published this trending research paper on September 17, 2019, entitled, "Consuming cholera toxin counteracts age-associated obesity" by researchers from the Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA; Department of infectious Diseases and Pathology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Greece.

Abstract:
During the past forty years there has been an inexplicable increase in chronic inflammatory disorders, including obesity. One theory, the ‘hygiene hypothesis’, involves dysregulated immunity arising after too few beneficial early life microbe exposures. Indeed, earlier studies have shown that gut microbe-immune interactions contribute to smoldering inflammation, adiposity, and weight gain. Here we tested a safe and well-established microbe-based immune adjuvant to restore immune homeostasis and counteract inflammation-associated obesity in animal models. We found that consuming Vibrio cholerae exotoxin subunit B (ctB) was sufficient to inhibit age-associated obesogenic outcomes in wild type mice, including reduced crown-like structures (CLS) and granulomatous necrosis histopathology in fat depots. Administration of cholera toxin reduced weight gain irrespective of age during administration; however, exposure during youth imparted greater slenderizing effects when compared with animals receiving ctB for the first time during adulthood. Beneficial effects were transplantable to other obesity-prone animals using immune cells alone, demonstrating an immune-mediated mechanism. Taken together, we concluded that oral vaccination with cholera toxin B helps stimulate health-protective immune responses that counteract age-associated obesity.

Press release - https://www.oncotarget.com/news/pr/consuming-cholera-toxin-counteracts-age-associated-obesity/

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DOI - https://doi.org/10.18632/oncotarget.27137

Full text - https://www.oncotarget.com/article/27137/text/

Correspondence to - Susan E. Erdman - serdman@mit.edu

Keywords - body weight, mouse, exotoxin subunit B, CLS, inflammation

About Oncotarget

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