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323 results on '"SHANKER, ANIL"'

6. Correction: Linking bacterial enterotoxins and alpha defensin 5 expansion in the Crohn’s colitis: A new insight into the etiopathogenetic and differentiation triggers driving colonic inflammatory bowel disease

Author

Rana, Tanu, primary, Korolkova, Olga Y., additional, Rachakonda, Girish, additional, Williams, Amanda D., additional, Hawkins, Alexander T., additional, James, Samuel D., additional, Sakwe, Amos M., additional, Nian, Hui, additional, Wang, Li, additional, Yu, Chang, additional, Goodwin, Jeffrey S., additional, Izban, Michael G., additional, Offodile, Regina S., additional, Washington, Mary K., additional, Ballard, Billy R., additional, Smoot, Duane T., additional, Shi, Xuan-Zheng, additional, Forbes, Digna S., additional, Shanker, Anil, additional, and M’Koma, Amosy E., additional

Published
2024
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8. Loss of Mitochondrial Tusc2/Fus1 Triggers a Brain Pro-Inflammatory Microenvironment and Early Spatial Memory Impairment.

Author

Farris, Tonie, González-Ochoa, Salvador, Mohammed, Muna, Rajakaruna, Harshana, Tonello, Jane, Kanagasabai, Thanigaivelan, Korolkova, Olga, Shimamoto, Akiko, Ivanova, Alla, and Shanker, Anil

Subjects
MEMORY disorders, SPATIAL memory, PATHOLOGICAL physiology, REGULATORY T cells, MEMORY loss, T cells, MITOCHONDRIAL membranes
Abstract

Brain pathological changes impair cognition early in disease etiology. There is an urgent need to understand aging-linked mechanisms of early memory loss to develop therapeutic strategies and prevent the development of cognitive impairment. Tusc2 is a mitochondrial-resident protein regulating Ca2+ fluxes to and from mitochondria impacting overall health. We previously reported that Tusc2−/− female mice develop chronic inflammation and age prematurely, causing age- and sex-dependent spatial memory deficits at 5 months old. Therefore, we investigated Tusc2-dependent mechanisms of memory impairment in 4-month-old mice, comparing changes in resident and brain-infiltrating immune cells. Interestingly, Tusc2−/− female mice demonstrated a pro-inflammatory increase in astrocytes, expression of IFN-γ in CD4+ T cells and Granzyme-B in CD8+T cells. We also found fewer FOXP3+ T-regulatory cells and Ly49G+ NK and Ly49G+ NKT cells in female Tusc2−/− brains, suggesting a dampened anti-inflammatory response. Moreover, Tusc2−/− hippocampi exhibited Tusc2- and sex-specific protein changes associated with brain plasticity, including mTOR activation, and Calbindin and CamKII dysregulation affecting intracellular Ca2+ dynamics. Overall, the data suggest that dysregulation of Ca2+-dependent processes and a heightened pro-inflammatory brain microenvironment in Tusc2−/− mice could underlie cognitive impairment. Thus, strategies to modulate the mitochondrial Tusc2- and Ca2+- signaling pathways in the brain should be explored to improve cognitive health. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Phase II Study of Immunotherapy With Tecemotide and Bevacizumab After Chemoradiation in Patients With Unresectable Stage III Non-Squamous Non–Small-Cell Lung Cancer (NS-NSCLC): A Trial of the ECOG-ACRIN Cancer Research Group (E6508)

Author

Patel, Jyoti D., Lee, Ju-Whei, Carbone, David P., Wagner, Henry, Shanker, Anil, de Aquino, Maria Teresa P., Horn, Leora, Johnson, Melissa L., Gerber, David E., Liu, Jane Jijun, Das, Millie S., Al-Nsour, Mohammed Ali, Dakhil, Christopher S.R., Ramalingam, Suresh, and Schiller, Joan H.

Published
2020
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11. Developing Ethics and Equity Principles, Terms, and Engagement Tools to Advance Health Equity and Researcher Diversity in AI and Machine Learning: Modified Delphi Approach

Author

Hendricks-Sturrup, Rachele, primary, Simmons, Malaika, additional, Anders, Shilo, additional, Aneni, Kammarauche, additional, Wright Clayton, Ellen, additional, Coco, Joseph, additional, Collins, Benjamin, additional, Heitman, Elizabeth, additional, Hussain, Sajid, additional, Joshi, Karuna, additional, Lemieux, Josh, additional, Lovett Novak, Laurie, additional, Rubin, Daniel J, additional, Shanker, Anil, additional, Washington, Talitha, additional, Waters, Gabriella, additional, Webb Harris, Joyce, additional, Yin, Rui, additional, Wagner, Teresa, additional, Yin, Zhijun, additional, and Malin, Bradley, additional

Published
2023
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12. Bortezomib Improves Adoptive T-cell Therapy by Sensitizing Cancer Cells to FasL Cytotoxicity

Author

Shanker, Anil, Pellom, Samuel T, Dudimah, Duafalia F, Thounaojam, Menaka C, de Kluyver, Rachel L, Brooks, Alan D, Yagita, Hideo, McVicar, Daniel W, Murphy, William J, Longo, Dan L, and Sayers, Thomas J

Subjects
Immunization, Rare Diseases, Vaccine Related, Cancer, 1.1 Normal biological development and functioning, 5.2 Cellular and gene therapies, Development of treatments and therapeutic interventions, Underpinning research, Animals, Antineoplastic Agents, Bortezomib, Combined Modality Therapy, Cytotoxicity, Immunologic, Fas Ligand Protein, Flow Cytometry, Humans, Immunoblotting, Immunohistochemistry, Immunotherapy, Adoptive, Kidney Neoplasms, Melanoma, Mice, Mice, Inbred BALB C, Mice, Knockout, T-Lymphocytes, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Cancer immunotherapy shows great promise but many patients fail to show objective responses, including in cancers that can respond well, such as melanoma and renal adenocarcinoma. The proteasome inhibitor bortezomib sensitizes solid tumors to apoptosis in response to TNF-family death ligands. Because T cells provide multiple death ligands at the tumor site, we investigated the effects of bortezomib on T-cell responses in immunotherapy models involving low-avidity antigens. Bortezomib did not affect lymphocyte or tissue-resident CD11c(+)CD8(+) dendritic cell counts in tumor-bearing mice, did not inhibit dendritic cell expression of costimulatory molecules, and did not decrease MHC class I/II-associated antigen presentation to cognate T cells. Rather, bortezomib activated NF-κB p65 in CD8(+) T cells, stabilizing expression of T-cell receptor CD3ζ and IL2 receptor-α, while maintaining IFNγ secretion to improve FasL-mediated tumor lysis. Notably, bortezomib increased tumor cell surface expression of Fas in mice as well as human melanoma tissue from a responsive patient. In renal tumor-bearing immunodeficient Rag2(-/-) mice, bortezomib treatment after adoptive T-cell immunotherapy reduced lung metastases and enhanced host survival. Our findings highlight the potential of proteasome inhibitors to enhance antitumor T-cell function in the context of cancer immunotherapy.

Published
2015

14. Bortezomib in Combination with Physachenolide C Reduces the Tumorigenic Properties of KRAS mut /P53 mut Lung Cancer Cells by Inhibiting c-FLIP.

Author

Kanagasabai, Thanigaivelan, Dunbar, Zerick, Ochoa, Salvador González, Farris, Tonie, Dhandayuthapani, Sivanesan, Wijeratne, E. M. Kithsiri, Gunatilaka, A. A. Leslie, and Shanker, Anil

Subjects
THERAPEUTIC use of antineoplastic agents, PROTEINS, IN vitro studies, BIOLOGICAL models, COMBINATION drug therapy, BIOLOGICAL products, ANIMAL experimentation, OXYGEN consumption, LUNG tumors, BORTEZOMIB, CANCER patients, CELL survival, CELL motility, COMPARATIVE studies, STEM cells, TOXICITY testing, DRUG synergism, DESCRIPTIVE statistics, RESEARCH funding, CELL lines, MICE, TRANSPLANTATION of organs, tissues, etc.
Abstract

Simple Summary: c-FLIP is a master anti-apoptotic regulator associated with resistance to various therapeutic options in different cancer types. Thus, exploring the combinatorial antitumor effects of a natural product, physachenolide C (PCC) and bortezomib, could lead to an effective, non-toxic therapeutic regimen against KRASmut/P53mut lung cancer cells. Our results showed that the bortezomib–PCC combination was more effective in reducing the viability and inhibiting migration and invasion of cancer cells. Additionally, c-FLIP protein expression was significantly inhibited along with a substantial reduction in the critical parameters of cellular metabolism in cancer cells. Strikingly, tumor growth inhibition was much more effective in tumor xenograft mice models with an enhanced efficacy without causing significant side effects. Background: Defects in apoptosis regulation are one of the classical features of cancer cells, often associated with more aggressiveness and failure to therapeutic options. We investigated the combinatorial antitumor effects of a natural product, physachenolide C (PCC) and bortezomib, in KRASmut/P53mut lung cancer cells and xenograft mice models. Methods: The in vitro anticancer effects of the bortezomib and PCC combination were investigated using cell viability, migration, and invasion assays in 344SQ, H23, and H358 cell lines. Furthermore, the effects of combination treatment on the critical parameters of cellular metabolism, including extracellular acidification rate (ECAR) and mitochondrial oxidative phosphorylation based on the oxygen consumption rate of cancer cells were assessed using Seahorse assay. Finally, the antitumor effect of the bortezomib (1 mg/kg) and PCC (10 mg/kg) combination was evaluated using xenograft mice models. Results: Our data showed that the bortezomib–PCC combination was more effective in reducing the viability of lung cancer cells in comparison with the individual treatments. Similarly, the combination treatment showed a significant inhibition of cell migration and invasion of cancer cells. Additionally, the key anti-apoptotic protein c-FLIP was significantly inhibited along with a substantial reduction in the key parameters of cellular metabolism in cancer cells. Notably, the bortezomib or PCC inhibited the tumor growth compared to the control group, the tumor growth inhibition was much more effective when bortezomib was combined with PCC in tumor xenograft mice models. Conclusion: These findings demonstrate that PCC sensitizes cancer cells to bortezomib, potentially improving the antitumor effects against KRASmut/P53mut lung cancer cells, with an enhanced efficacy of combination treatments without causing significant side effects. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Improving combination therapies: targeting A2B-adenosine receptor to modulate metabolic tumor microenvironment and immunosuppression

Author

Evans, Jason V, primary, Suman, Shankar, additional, Goruganthu, Mounika Uttam L, additional, Tchekneva, Elena E, additional, Guan, Shuxiao, additional, Arasada, Rajeswara Rao, additional, Antonucci, Anneliese, additional, Piao, Longzhu, additional, Ilgisonis, Irina, additional, Bobko, Andrey A, additional, Driesschaert, Benoit, additional, Uzhachenko, Roman V, additional, Hoyd, Rebecca, additional, Samouilov, Alexandre, additional, Amann, Joseph, additional, Wu, Ruohan, additional, Wei, Lai, additional, Pallerla, Aaditya, additional, Ryzhov, Sergey V, additional, Feoktistov, Igor, additional, Park, Kyungho P, additional, Kikuchi, Takefumi, additional, Castro, Julio, additional, Ivanova, Alla V, additional, Kanagasabai, Thanigaivelan, additional, Owen, Dwight H, additional, Spakowicz, Daniel J, additional, Zweier, Jay L, additional, Carbone, David P, additional, Novitskiy, Sergey V, additional, Khramtsov, Valery V, additional, Shanker, Anil, additional, and Dikov, Mikhail M, additional

Published
2023
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20. Data from Multivalent Forms of the Notch Ligand DLL-1 Enhance Antitumor T-cell Immunity in Lung Cancer and Improve Efficacy of EGFR-Targeted Therapy

Author

Biktasova, Asel K., primary, Dudimah, Duafalia F., primary, Uzhachenko, Roman V., primary, Park, Kyungho, primary, Akhter, Anwari, primary, Arasada, Rajeswara R., primary, Evans, Jason V., primary, Novitskiy, Sergey V., primary, Tchekneva, Elena E., primary, Carbone, David P., primary, Shanker, Anil, primary, and Dikov, Mikhail M., primary

Published
2023
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21. Data from Small-Molecule Natural Product Physachenolide C Potentiates Immunotherapy Efficacy by Targeting BET Proteins

Author

Tewary, Poonam, primary, Brooks, Alan D., primary, Xu, Ya-Ming, primary, Wijeratne, E.M. Kithsiri, primary, Babyak, Ashley L., primary, Back, Timothy C., primary, Chari, Raj, primary, Evans, Christine N., primary, Henrich, Curtis J., primary, Meyer, Thomas J., primary, Edmondson, Elijah F., primary, de Aquino, Maria T. Prudente, primary, Kanagasabai, Thanigaivelan, primary, Shanker, Anil, primary, Gunatilaka, A.A. Leslie, primary, and Sayers, Thomas J., primary

Published
2023
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22. Supplementary Figure S1 from Multivalent Forms of the Notch Ligand DLL-1 Enhance Antitumor T-cell Immunity in Lung Cancer and Improve Efficacy of EGFR-Targeted Therapy

Author

Biktasova, Asel K., primary, Dudimah, Duafalia F., primary, Uzhachenko, Roman V., primary, Park, Kyungho, primary, Akhter, Anwari, primary, Arasada, Rajeswara R., primary, Evans, Jason V., primary, Novitskiy, Sergey V., primary, Tchekneva, Elena E., primary, Carbone, David P., primary, Shanker, Anil, primary, and Dikov, Mikhail M., primary

Published
2023
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23. Supplementary Data from Small-Molecule Natural Product Physachenolide C Potentiates Immunotherapy Efficacy by Targeting BET Proteins

Author

Tewary, Poonam, primary, Brooks, Alan D., primary, Xu, Ya-Ming, primary, Wijeratne, E.M. Kithsiri, primary, Babyak, Ashley L., primary, Back, Timothy C., primary, Chari, Raj, primary, Evans, Christine N., primary, Henrich, Curtis J., primary, Meyer, Thomas J., primary, Edmondson, Elijah F., primary, de Aquino, Maria T. Prudente, primary, Kanagasabai, Thanigaivelan, primary, Shanker, Anil, primary, Gunatilaka, A.A. Leslie, primary, and Sayers, Thomas J., primary

Published
2023
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24. Supplementary Table S1 from Multivalent Forms of the Notch Ligand DLL-1 Enhance Antitumor T-cell Immunity in Lung Cancer and Improve Efficacy of EGFR-Targeted Therapy

Author

Biktasova, Asel K., primary, Dudimah, Duafalia F., primary, Uzhachenko, Roman V., primary, Park, Kyungho, primary, Akhter, Anwari, primary, Arasada, Rajeswara R., primary, Evans, Jason V., primary, Novitskiy, Sergey V., primary, Tchekneva, Elena E., primary, Carbone, David P., primary, Shanker, Anil, primary, and Dikov, Mikhail M., primary

Published
2023
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42. Correction to: Determinant roles of dendritic cell-expressed Notch Delta-like and Jagged ligands on anti-tumor T-cell immunity

Author

Tchekneva, Elena E., Goruganthu, Mounika U. L., Uzhachenko, Roman V., Thomas, Portia L., Antonucci, Anneliese, Chekneva, Irina, Koenig, Michael, Piao, Longzhu, Akhter, Anwari, de Aquino, Maria Teresa P., Ranganathan, Parvathi, Long, Nicholas, Magliery, Thomas, Valujskikh, Anna, Evans, Jason V., Arasada, Rajeswara R., Massion, Pierre P., Carbone, David P., Shanker, Anil, and Dikov, Mikhail M.

Published
2019
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43. Determinant roles of dendritic cell-expressed Notch Delta-like and Jagged ligands on anti-tumor T cell immunity

Author

Tchekneva, Elena E., Goruganthu, Mounika U.L., Uzhachenko, Roman V., Thomas, Portia L., Antonucci, Anneliese, Chekneva, Irina, Koenig, Michael, Piao, Longzhu, Akhter, Anwari, de Aquino, Maria Teresa P., Ranganathan, Parvathi, Long, Nicholas, Magliery, Thomas, Valujskikh, Anna, Evans, Jason V., Arasada, Rajeswara R., Massion, Pierre P., Carbone, David P., Shanker, Anil, and Dikov, Mikhail M.

Published
2019
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