Palak A. Shah

Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a groundbreaking modality in cancer immunotherapy, offering remarkable clinical benefits, particularly in hematologic malignancies. By genetically reprogramming autologous T-cells to express synthetic receptors targeting tumor-specific antigens, CAR T-cells can mediate robust antitumor responses. This review provides a comprehensive overview of CAR T-cell immunotherapy, including its historical development, structural design, mechanism of action, and preclinical and clinical evolution. We highlight the intricacies of the tumor immune microenvironment, immune evasion mechanisms employed by cancer cells, and how CAR T-cells address these barriers. FDA-approved CAR T-cell therapies for B-cell malignancies and the current landscape of clinical trials for both liquid and solid tumors are critically analyzed. Furthermore, we explore novel targets, combination strategies, and technological innovations aimed at enhancing CAR T-cell efficacy and overcoming challenges related to antigen heterogeneity, toxicity, and resistance. Issues surrounding cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and tumor antigen escape are also discussed. The review delves into ongoing efforts in preclinical models, translational advancements, and emerging approaches such as dual-targeting CARs, armored CARs, and alternative co-stimulatory domains. Finally, the ethical, economic, and logistical challenges associated with CAR T-cell therapy are examined, including access disparities, manufacturing constraints, and the need for value-based pricing models. By synthesizing current insights and future directions, this review emphasizes transformative role of CAR T-cell therapy in oncology and the imperative for continued innovation to extend its benefits to broader patient populations. Graphical abstract Overview of CAR T-Cell Immunotherapy in Cancer Management. This figure illustrates the current landscape and challenges of CAR T-cell therapy. Left panel: CAR T-cells are engineered to recognize tumor-specific antigens and are infused into patients to target both hematologic (liquid) and solid tumors. Upon engagement, CAR T-cells release effector cytokines (IFN-γ, TNF-α) to induce tumor cell death. Key clinical hurdles include cytokine release syndrome (CRS), tumor antigen escape, and limited efficacy in solid tumors due to immune evasion mechanisms within the tumor microenvironment (TME). Right panel: The figure also highlights the dynamic interplay between cancer and innate/adaptive immune cells, showcasing the immunosuppressive milieu and the ongoing battle between immune recognition and tumor evasion strategies.

Background Disabled 2 (DAB2) is a multifunctional protein that has emerged as a critical component in the regulation of tumor growth. Its dysregulation is implicated in various types of cancer, underscoring its importance in understanding the molecular mechanisms underlying tumor development and progression. This review aims to unravel the intricate molecular mechanisms by which DAB2 exerts its tumor-suppressive functions within cancer signaling pathways. Methods and results We conducted a comprehensive review of the literature focusing on the structure, expression, physiological functions, and tumor-suppressive roles of DAB2. We provide an overview of the structure, expression, and physiological functions of DAB2. Evidence supporting DAB2's role as a tumor suppressor is explored, highlighting its ability to inhibit cell proliferation, induce apoptosis, and modulate key signaling pathways involved in tumor suppression. The interaction between DAB2 and key oncogenes is examined, elucidating the interplay between DAB2 and oncogenic signaling pathways. We discuss the molecular mechanisms underlying DAB2-mediated tumor suppression, including its involvement in DNA damage response and repair, regulation of cell cycle progression and senescence, and modulation of epithelial-mesenchymal transition (EMT). The review explores the regulatory networks involving DAB2, covering post-translational modifications, interactions with other tumor suppressors, and integration within complex signaling networks. We also highlight the prognostic significance of DAB2 and its role in pre-clinical studies of tumor suppression. Conclusion This review provides a comprehensive understanding of the molecular mechanisms by which DAB2 exerts its tumor-suppressive functions. It emphasizes the significance of DAB2 in cancer signaling pathways and its potential as a target for future therapeutic interventions. Graphical Abstract

Uricosuric activity of different extracts of Tinospora cordifolia was studied in hyperuricemia induced in albino Wistar rat using potassium oxonate. The uric acid level in serum and urine were measured. Uricosuric activity was also evaluated using phenol red dye excretion model. Phenol red levels were measured in blood. In potassium oxonate induced hyperuricemia, probenecid, aqueous, hydro-alcoholic, dichloromethane extract and galo satwa (starch of T. cordifolia) significantly lowered the serum uric acid levels. All the extracts increased uric acid excretion and decreased the elevated serum uric acid levels induced due to potassium oxonate. Probenecid, aqueous extract and galo satwa significantly increased fractional excretion of uric acid and phenol red levels in blood indicating uricosuria. Polysaccharides in aqueous extract and galo satwa may be responsible for uricosuric action. Video ClipsPreparation of extracts 4 min 22 secPrepared extracts 26 sec Potassium oxonate induced hyperurecimia 1 min 46 secInjection of red phenol into tail vein 52 secCollection of blood 16 secEstimation of uric acid 1 min 44 sec