https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/35 Principal Investigator- Dr. Anil Suri 2026-04-27T15:41:15Z https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1541 Title: Gut Metabolite Indoxyl Sulfate Has Selective Deleterious and Anticancer Effect on Colon Cancer Cells Authors: Dalal, Nishu; Makharia, Govind K; Dalal, Monu; Mohan, Anand; Singh, Rajeev; Kumar, Anil Abstract: There are a number of reports about anticancer activity of indole derivatives. In this study, we investigated the role of indoxyl sulfate (IS) for its selective anticancer activity on colon cancer cells. IS treatment on HCT-116 and HT-29 human epithelial adenocarcinoma cells led to a decrease in cell proliferation, cell viability, and ATP content. Colon cancer cells showed a 10% increase in cell apoptosis in comparison to control. Due to IS treatment, cell morphology got distorted, cell number found decreased, intracellular vesicles formed, and cells were found floating in the media. Cells also showed a loss in membrane integrity and a decrease in colony-forming ability and ceased at the G2/M phase of the cell cycle. No significant change was noted in the level of inflammatory cytokines IL-17A, IL-1β, and TNF-α, histology, length of intestine, and spleen after 100 mM IS treatment to balb/c mice. These observations indicate the selective anticancer effect of IS on colon cancer cells. 2023-01-01T00:00:00Z https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1523 Title: Optimization and Validation of a Harmonized Protocol for Generating Therapeutic-Grade Dendritic Cells in a Randomized Phase II Clinical Trial, Using Two Varied Antigenic Sources Authors: Seetharaman, Abirami; Christopher, Vasanth; Dhandapani, hemavati; Jayakumar, Hascitha; Dhanushkodi, Manikandan; Bhaskaran, Narmadha; Rajaraman, Swaminathan; Ranganathan, Rama; Singh, Shirley Sunder; Vijayakumar, Varalakshmi; Rajamanickam, Arivazhagan; Suri, Anil; Jagadish, Nirmala; Rajkumar, Thangarajan; Ramanathan, Priya Abstract: Autologous dendritic cell (DC)-based immunotherapy is a cell-based advanced therapy medicinal product (ATMP) that was first introduced more than three decades ago. In the current study, our objective was to establish a harmonized protocol using two varied antigenic sources and a good manufacturing practice (GMP)-compliant, manual method for generating clinical-grade DCs at a limited-resource academic setting. After obtaining ethical committee-approved informed consent, the recruited patients underwent leukapheresis, and single-batch DC production was carried out. Using responder-independent flow cytometric assays as quality control (QC) criteria, we propose a differentiation and maturation index (DI and MI, respectively), calculated with the QC cut-off and actual scores of each batch for comparison. Changes during cryopreservation and personnel variation were assessed periodically for up to two to three years. Using our harmonized batch production protocol, the average DI was 1.39 and MI was 1.25. Allogenic responder proliferation was observed in all patients, while IFN-gamma secretion, evaluated using flow cytometry, was detected in 10/36 patients and significantly correlated with CD8+ T cell proliferation (p value-0.0002). Tracking the viability and phenotype of cryopreserved MDCs showed a >90% viability for up to three years, while a mature DC phenotype was retained for up to one year. Our results confirm that the manual/semi-automated protocol was simple, consistent, and cost-effective, without the requirement for expensive equipment and without compromising on the quality of the final product. 2024-01-01T00:00:00Z https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1522 Title: Optimization and Validation of a Harmonized Protocol for Generating Therapeutic-Grade Dendritic Cells in a Randomized Phase II Clinical Trial, Using Two Varied Antigenic Sources Authors: Abirami Seetharaman, Abirami; Christopher, Vasanth; Dhandapani, Hemavathi; kumar, Hascitha; Dhanushkodi, Jaya; Bhaskaran, Narmadha; Rajaraman, Swaminathan; Ranganathan, Rama; Singh, Shirley Sunder; Vijayakumar, Varalakshmi; Rajamanickam, Arivazhagan; Suri, Anil; Jagadish, Nirmala; Rajkumar, Thangarajan; Ramanathan, Priya Abstract: Autologous dendritic cell (DC)-based immunotherapy is a cell-based advanced therapy medicinal product (ATMP) that was first introduced more than three decades ago. In the current study, our objective was to establish a harmonized protocol using two varied antigenic sources and a good manufacturing practice (GMP)-compliant, manual method for generating clinical-grade DCs at a limited-resource academic setting. After obtaining ethical committee-approved informed consent, the recruited patients underwent leukapheresis, and single-batch DC production was carried out. Using responder-independent flow cytometric assays as quality control (QC) criteria, we propose a differentiation and maturation index (DI and MI, respectively), calculated with the QC cut-off and actual scores of each batch for comparison. Changes during cryopreservation and personnel variation were assessed periodically for up to two to three years. Using our harmonized batch production protocol, the average DI was 1.39 and MI was 1.25. Allogenic responder proliferation was observed in all patients, while IFN-gamma secretion, evaluated using flow cytometry, was detected in 10/36 patients and significantly correlated with CD8+ T cell proliferation (p value-0.0002). Tracking the viability and phenotype of cryopreserved MDCs showed a >90% viability for up to three years, while a mature DC phenotype was retained for up to one year. Our results confirm that the manual/semi-automated protocol was simple, consistent, and cost-effective, without the requirement for expensive equipment and without compromising on the quality of the final product. 2024-01-01T00:00:00Z https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1362 Title: Role of A-Kinase anchor protein (AKAP4) in growth and survival of ovarian cancer cells Authors: Suri, Anil; Kumar, Vikash; Jagadish, Nirmala Abstract: Ovarian cancer represents one of the most common malignancies among women with very high mortality rate worldwide. A-kinase anchor protein 4 (AKAP4), a unique cancer testis (CT) antigen has been shown to be associated with various malignant properties of cancer cells. However, its involvement in various molecular pathways in ovarian cancer remains unknown. In present investigation, employing gene silencing approach, we examined the role of AKAP4 in cell cycle, apoptosis and epithelial-mesenchymal transition (EMT). Further, we also investigated the effect of ablation of AKAP4 on tumor growth in SCID mice ovarian cancer xenograft mouse model. Our results showed that ablation of AKAP4 resulted in increased reactive oxygen species (ROS) generation, DNA damage, cell cycle arrest and apoptosis in ovarian cancer cells. AKAP4 knockdown lead to degradation of protien kinase A (PKA) which was rescued by proteosome inhibitor MG-132. ROS quencher N-acetyl cysteine (NAC) treatment rescued cell cycle arrest and resumed cell division. Subsequently, increased expression of pro-apoptotic molecules and decreased expression of pro-survival/anti-apoptotic factors was observed. As a result of AKAP4 depletion, DNA damage response proteins p-γH2AX, p-ATM and p21 were upregulated. Also, knockdown of CREB resulted in similar findings. Further, PKA inhibitor (H89) and oxidative stress resulted in similar phenotype of ovarian cancer cells as observed in AKAP4 ablated cells. Collectively, for the first time our data showed the involvement of AKAP4 in PKA degradation and perturbed signaling through PKA-CREB axis in AKAP4 ablated ovarian cancer cells. 2017-01-01T00:00:00Z