Chimeric antigen receptor (CAR) T cell therapy represents a major breakthrough in cancer care since the approval of tisagenlecleucel by the Food and Drug Administration in 2017 for the treatment of pediatric and young adult patients with relapsed or refractory acute lymphocytic leukemia. As of April 2023, six CAR T cell therapies have been approved, demonstrating unprecedented efficacy in patients with B-cell malignancies and multiple myeloma. However, adverse events such as cytokine release syndrome and immune effector cell-associated neurotoxicity pose significant challenges to CAR T cell therapy. The severity of these adverse events correlates with the pretreatment tumor burden, where a higher tumor burden results in more severe consequences. This observation is supported by the application of CD19-targeted CAR T cell therapy in autoimmune diseases including systemic lupus erythematosus and antisynthetase syndrome. These results indicate that initiating CAR T cell therapy early at low tumor burden or using debulking strategy prior to CAR T cell infusion may reduce the severity of adverse events. In addition, CAR T cell therapy is expensive and has limited effectiveness against solid tumors. In this article, we review the critical steps that led to this groundbreaking therapy and explore ongoing efforts to overcome these challenges. With the promise of more effective and safer CAR T cell therapies in development, we are optimistic that a broader range of cancer patients will benefit from this revolutionary therapy in the foreseeable future.

The present study primarily intends to document how textbooks and reference textbooks on film studies written by Western and diaspora authors either belittled Indian cinema as masala genre or glorified the moniker Bollywood as a signifier of pan-Indianness, overlooking the significant contributions of the Telugu film industry, which is the twin brother of the Hindi film industry both in genesis and growth (since 1931) and even today runs neck to neck with Hindi cinema in the production of films and film remakes. The study argues that Indian cinema has never been examined at the modernist (foundation) level of its structural perspectives comprising innovations of production, cultural flows in the delineation of regional variations, and fine arts including aesthetics consisting of six arts and genres that are native, distinct, and unique. Drawing its support from de-Westernizing media studies, the article posits that lack of familiarity with the Indian cultural and linguistic traditions, together with its complex structure and semiotics rooted in religious classics, which are portrayed more effectively in Telugu cinema than in Hindi cinema, is the reason for the failure of

Prostate cancer is the most commonly diagnosed noncutaneous cancer in American men. TDRD1, a germ cell-speci c gene, is erroneously expressed in more than half of prostate tumors, but its role in prostate cancer development remains elusive. In this study, we identi ed a PRMT5-TDRD1 signaling axis that regulates the proliferation of prostate cancer cells. PRMT5 is a protein arginine methyltransferase essential for small nuclear ribonucleoprotein (snRNP) biogenesis. Methylation of Sm proteins by PRMT5 is a critical initiation step for assembling snRNPs in the cytoplasm, and the nal snRNP assembly takes place in Cajal bodies in the nucleus. By mass spectrum analysis, we found that TDRD1 interacts with multiple subunits of the snRNP biogenesis machinery. In the cytoplasm, TDRD1 interacts with methylated Sm proteins in a PRMT5-dependent manner. In the nucleus, TDRD1 interacts with Coilin, the scaffold protein of Cajal bodies. Ablation of TDRD1 in prostate cancer cells disrupted the integrity of Cajal bodies, affected the snRNP biogenesis, and reduced cell proliferation. Taken together, this study represents the rst characterization of TDRD1 functions in prostate cancer development and suggests TDRD1 as a potential therapeutic target for prostate cancer treatment.GCA ATA GT-5') and the non-targeting control vector(U-009501-01-02) were obtained from Dharmacon (CO, USA). The ERG lentiviral sgRNA vector was purchased from Sigma-Aldrich with the sgRNA sequence: 5'-CCG TGG AGA GTT TTG TAA GGC T-3'. VCaP cells were transduced with lentivirus expressing Cas9 and then selected with 5 µg/ml blasticidin (Sigma-Aldrich #15205), followed by transduction with lentiviruses containing TDRD1 and ERG sgRNAs and control, followed by a selection of 5 µg/ml puromycin (Sigma-Aldrich #P8833). Cell growth assayVCaP, 22Rv1, and LNCaP cells were seeded at a density of 1 × 10 4 cells per well in at-bottomed 96-well plates and grew for 3-11 days. CellTiter-Glo® Luminescent Cell Viability Assay (Promega, Madison, WI, USA) was used to measure cell viability every other day, and the luminescence was determined by Synergy™ neo2 multi-mode reader (BioTek, Winooski, VT, USA).

Altodi Poltodi thinks through aspects of permeability and preservation, provoking an image of shadowy protector figures. How do they interact with a landscape, what could they want to protect and where do they mark their boundary lines? Drawing from the ancient stories of Rakhandars, mythic beings that guard or protect Goan villages, this collaborative process weaves personal stories with the land and history of Goa. Altodi Poltodi began as a conversation between two friends on a bridge over a river, in a state of suspension, connecting two shores – those of memory and the present.

Prostate cancer is the most commonly diagnosed noncutaneous cancer in American men. TDRD1, a germ cell-specific gene, is erroneously expressed in more than half of prostate tumors, but its role in prostate cancer development remains elusive. In this study, we identified a PRMT5-TDRD1 signaling axis that regulates the proliferation of prostate cancer cells. PRMT5 is a protein arginine methyltransferase essential for small nuclear ribonucleoprotein (snRNP) biogenesis. Methylation of Sm proteins by PRMT5 is a critical initiation step for assembling snRNPs in the cytoplasm, and the final snRNP assembly takes place in Cajal bodies in the nucleus. By mass spectrum analysis, we found that TDRD1 interacts with multiple subunits of the snRNP biogenesis machinery. In the cytoplasm, TDRD1 interacts with methylated Sm proteins in a PRMT5-dependent manner. In the nucleus, TDRD1 interacts with Coilin, the scaffold protein of Cajal bodies. Ablation of TDRD1 in prostate cancer cells disrupted the integrity of Cajal bodies, affected the snRNP biogenesis, and reduced cell proliferation. Taken together, this study represents the first characterization of TDRD1 functions in prostate cancer development and suggests TDRD1 as a potential therapeutic target for prostate cancer treatment.