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Study identifies two genes that play key role in protecting ovarian cancer from the immune system

New mechanism by which senescent cells turn on genes encoding for tumor-regulating factors

Credit: The Wistar Institute PHILADELPHIA (April 1, 2021 Scientists at The Wistar Institute identified a new mechanism of transcriptional control of cellular senescence that drives the release of inflammatory molecules that influence tumor development through altering the surrounding microenvironment. The study, published in Nature Cell Biology, reports that methyltransferase-like 3 (METTL3) and 14 (METTL14) proteins moonlight as transcriptional regulators that allow for establishment of the senescence-associated secretory phenotype (SASP). Cellular senescence is a stable state of growth arrest in which cells stop dividing but remain viable and produce an array of inflammatory and growth-promoting molecules collectively defined as SASP. These molecules account for the complex crosstalk between senescent cells and neighboring cells and the effect of cellular senescence in various physiological processes and diseases. Although senescence is regarded as a potent barrier for tum

Jubilant Therapeutics Announces Research Collaboration with The Wistar Institute to Evaluate the Activity of Novel PAD4 Inhibitors to Reduce Clinical Severity of COVID-19

(1) BEDMINSTER, N.J., Jan. 15, 2021 /PRNewswire/ Jubilant Therapeutics Inc., a biopharmaceutical company advancing small molecule modulators to address unmet medical needs in oncology and autoimmune diseases, today announced a collaboration with The Wistar Institute, an international leader in biomedical research, to evaluate the ability of Peptidyl Arginine Deiminase 4 (PAD4) inhibitors provided by Jubilant Therapeutics to block neutrophil extracellular trap (NET) formation in the context of COVID-19 related cytokine storms. PAD4 is an enzyme that catalyzes conversion of arginine to citrulline in proteins, including histones and is highly expressed in neutrophils. Histone citrullination has been implicated in Neutrophil Extracellular Trap (NET) formation and accumulating evidence suggests that NETs may be linked to the severity of COVID-19, as their formation is a result of pro-inflammatory cytokine release syndrome (CRS), or cytokine storms, produced by the body s immune resp

Researchers Identify Link Between Ovarian Cancer, Metabolism

Researchers Identify Link Between Ovarian Cancer, Metabolism by Angela Mohan on  January 12, 2021 at 5:24 PM Nature Cancer. Up to 60% of ovarian clear cell carcinomas (OCCC) have inactivating mutations in the ARID1A tumor suppressor gene. These mutations are known genetic drivers of this type of cancer, which typically does not respond to chemotherapy and carries the worst prognosis among all subtypes of ovarian cancer. The laboratory of Rugang Zhang, Ph.D., deputy director of The Wistar Institute Cancer Center, professor and leader of the Immunology, Microenvironment & Metastasis Program, studies the effects of ARID1A inactivation to devise new mechanism-guided therapeutic strategies and combination approaches to enhance immunotherapy for ovarian cancer.

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