Browsing by Author "Avadhesh"

Now showing 1 - 3 of 3
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    Immune checkpoint molecules in neuroblastoma: A clinical perspective
    (Academic Press, 2022) Pathania, Anup S.; Prathipati, Philip; Murakonda, Swati P.; Murakonda, Ajay B.; Srivastava, Ankit; Avadhesh; Byrareddy, Siddappa N.; Coulter, Don W.; Gupta, Subash C.; Challagundla, Kishore B.
    High-risk neuroblastoma (NB) is challenging to treat with 5-year long-term survival in patients remaining below 50% and low chances of survival after tumor relapse or recurrence. Different strategies are being tested or under evaluation to destroy resistant tumors and improve survival outcomes in NB patients. Immunotherapy, which uses certain parts of a person's immune system to recognize or kill tumor cells, effectively improves patient outcomes in several types of cancer, including NB. One of the immunotherapy strategies is to block immune checkpoint signaling in tumors to increase tumor immunogenicity and anti-tumor immunity. Immune checkpoint proteins put brakes on immune cell functions to regulate immune activation, but this activity is exploited in tumors to evade immune surveillance and attack. Immune checkpoint proteins play an essential role in NB biology and immune escape mechanisms, which makes these tumors immunologically cold. Therapeutic strategies to block immune checkpoint signaling have shown promising outcomes in NB but only in a subset of patients. However, combining immune checkpoint blockade with other therapies, including conjugated antibody-based immunotherapy, radioimmunotherapy, tumor vaccines, or cellular therapies like modified T or natural killer (NK) cells, has shown encouraging results in enhancing anti-tumor immunity in the preclinical setting. An analysis of publicly available dataset using computational tools has unraveled the complexity of multiple cancer including NB. This review comprehensively summarizes the current information on immune checkpoint molecules, their biology, role in immune suppression and tumor development, and novel therapeutic approaches combining immune checkpoint inhibitors with other therapies to combat high-risk NB. � 2022
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    Moringin, an isothiocyanate modulates multiple cellular signalling molecules in breast cancer cells
    (Elsevier Inc., 2024) Srivastava A.; Mishra S.; Avadhesh; Shekher A.; Rai V.; Dhasmana A.; Das J.; Perenzoni D.; Iori R.; Gupta S.C.
    Prohibitin (PHB) is a pleiotropic molecule with a variety of known functions and subcellular locations. PHB's function in breast cancer is poorly understood. Herein, we report that PHB is expressed in cancer types of diverse origin including breast cancer. The cancer patients with changes in PHB were reported to have significantly reduced �overall survival� in comparison to the cases without alterations in PHB. The expression of PHB was increased by H2O2 and also by Moringin (MG), which is an isothiocyanate derived from the seeds of Moringa oleifera. MG interacted with PHB, DRP1, and SLP2 and inhibited the growth of MCF-7 and MDAMB-231 cells. The isothiocyanate triggered apoptosis in breast cancer cells as revealed by AO/PI assay, phosphatidylserine externalization, cell cycle analysis and DAPI staining. MG induced proapoptotic proteins expression such as cytochrome c, p53, and cleaved caspase-7. Further, cell survival proteins such as survivin, Bcl-2, and Bcl-xL were suppressed. A depolarization of membrane potential suggested that the apoptosis was triggered through mitochondria. The isothiocyanate suppressed the cancer cell migration and interacted with NF-?B subunits. MG suppressed p65 nuclear translocation induced by TNF-?. The reactive oxygen species generation was also induced by the isothiocyanate in breast cancer cells. MG also modulated the expression of lncRNAs. Collectively, the functions of PHB in breast cancer growth is evident from this study. The activities of MG against breast cancer might result from its ability to modulate multiple cancer-related targets. � 2023
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    Role of IL-1 gene polymorphisms in common solid cancers
    (Elsevier, 2023) Singh, Ragini D.; Dholariya, Sagar; Shekher, Anusmita; Avadhesh; Parchwani, Deepak; Gupta, Subash C.
    Because of the strong association of inflammation with cancer, the master cytokine, interleukin-1 (IL-1), has been extensively researched for its role in carcinogenesis. An appropriate, limited, targeted inflammatory response may provide protection to the host. However, on the other hand, an unusually protracted or severe inflammatory response may generate a microenvironment conducive to carcinogenesis. Inherited variants in the IL-1 gene affect its expression and eventually the molecular physiology of the IL-1 system. Studies have reported a wide variety of genetic variations inside the IL-1 gene cluster. Also, interpopulation differences in the distribution of polymorphic IL-1 genotypes are widespread. The polymorphic forms exert effects on cancer risk, development, and progression. This chapter focuses on the structure of the IL-1 gene, the polymorphisms reported in the IL-1 prototypes, i.e., IL1A, IL1B, and IL1RN, and the current knowledge on the involvement of polymorphic forms of IL-1 prototypes in cancer predisposition and prognosis, with particular emphasis on solid tumors. � 2023 Elsevier Inc. All rights reserved.