Browsing by Author "Sharma, Ashok"

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    Impact of noncoding RNAs on cancer directed immune therapies: Now then and forever
    (John Wiley and Sons Inc, 2022-04-30T00:00:00) Roy, Roshan Kumar; Yadav, Rakhi; Sharma, Uttam; Wasson, Mishi Kaushal; Sharma, Ashok; Tanwar, Pranay; Jain, Aklank; Prakash, Hridayesh
    Accumulating evidence demonstrates that the host genome's epigenetic modifications are essential for living organisms to adapt to extreme conditions. DNA methylation, covalent modifications of histone and interassociation of noncoding RNAs facilitate the cellular manifestation of epigenetic changes in the genome. Out of various factors involved in the epigenetic programming of the host, noncoding RNAs (ncRNAs) such as microRNA (miRNA), long noncoding RNA (lncRNA), circular RNA, snoRNA and piRNA are new generation noncoding molecules that influence a variety of cellular processes like immunity, cellular differentiation and tumor development. During tumor development, temporal changes in miRNA/lncRNA rheostat influence sterile inflammatory responses accompanied by the changes in the carcinogenic signaling in the host. At the cellular level, this is manifested by the upregulation of inflammasome and inflammatory pathways, which promotes cancer-related inflammation. Given this, we discuss the potential of lncRNAs, miRNAs, circular RNA, snoRNA and piRNA in regulating inflammation and tumor development in the host. � 2022 UICC.
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    Low dose radiation primed iNOS + M1macrophages modulate angiogenic programming of tumor derived endothelium.
    (PLOS, 2018) Nadella, Vinod; Singh Sandhya; Jain, Aklank; Jain, Manju; Vasquez, Karen M.; Sharma, Ashok; Tanwar, Pranay; Rath, Goura Kishore; Prakash Hridayesh.
    Solid tumors are covered by stroma, which is hypoxic in nature and composed of various non‐malignant components such as endothelial cells, fibroblasts, and pericytes that support tumor growth. Tumor stroma represents a mechanical barrier for tumor infiltration of CD8+ effector T cells in particular. In this context, our previous studies have demonstrated the therapeutic impact of Low‐Dose Radiation (LDR)‐primed and M1‐retuned (iNOS+) peritumoral macrophages that produce inducible nitric oxide, have immunological roles on tumor infiltration of effector T cells, cancer‐related inflammation, and subsequent tumor immune rejection in a mouse model of pancreatic cancer. These findings suggested a possible modification of tumor endothelium by LDR‐primed macrophages. In line with these observations, here we demonstrate the influence of LDR in down‐modulating HIF‐1 in irradiated tumors in the course of polarization of irradiated tumor‐associated macrophages toward an M1 phenotype. Furthermore, we demonstrate that M1 macrophages which are primed by LDR can directly influence angiogenic responses in eNOS+ endothelial cells which produce nitric oxide having both vascular and physiological roles. Furthermore, we demonstrate that naïve macrophages, upon differentiating to an M1 phenotype either by Th1 stimuli or LDR, potentially modify sphingosine‐1‐phosphate/VEGF‐induced angiogenic signaling in tumor‐derived endothelial cells with tumorigenic potential, thus indicating the significance of iNOS+ macrophages in modulating signaling in eNOS+ tumor‐derived endothelium. Our study suggests that iNOS+ macrophages can activate tumor endothelium which may contribute to cancer‐directed immunotherapy in particular.