Background/Aim: Wilms' tumor 1 (WT1) is involved in the development of the urogenital system and is expressed in podocytes throughout life. Inflammation of renal glomeruli causes renal damage-induced nephrotic syndrome and steroid-resistant nephrotic syndrome have mutations in the WT1 gene. The aim of this work was to determine if the inflammatory process modulates the expression and localization of WT1 in podocytes that cause kidney damage using lipopolysaccharide (LPS)-treated mice as a sepsis model. Materials and Methods: In investigation of renal damage, proteinuria and histology were analyzed. WT1 modulation was analyzed by indirect immunofluorescence, immunohistochemistry and western blot assays, and proinflammatory cytokines were analyzed by quantitative polymerase chain reaction assay. Results: WT1 expression decreased most at 24 and 36 h after the induction of inflammation and phosphorylated WT1 was mainly localized in the cytoplasm, reduced nephrin mRNA expression and increased mRNA expression of tumor necrosis factor α and interleukin 1β. Conclusion: These results indicate that the immune system plays an important role in the modulation of WT1, leading to kidney damage.

Background/Aim: Prostate apoptosis response 4 (PAR4), a tumour-suppressor protein, selectively induces apoptosis of cancer cells without affecting normal cells. Its soluble form is induced by secretagogues (e.g., chloroquine), and it induces apoptosis by interacting with the receptor of glucose-regulated protein 78, which is overexpressed in cancer cells. In this study, curcumin was analyzed as an inducer of PAR4 expression in 4T1 murine breast cancer cell. and its ability to induce PAR4 secretion in Balb/c mice. In addition, the cisplatin sensitizing effect of soluble PAR4 was analyzed. Material and Methods: The 4T1 cell line was treated in vitro using different concentrations of curcumin; cell viability was analyzed using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay and PAR4 expression by western blotting. The expression of soluble PAR4 in the serum of mice treated with intraperitoneal curcumin was analyzed using the dot-blot method. Moreover, MTT assay was used to analyze the effects of serum from curcumin-treated mice on cell viability. Tumor size was analyzed in mice treated with curcumin alone and in combination with cisplatin. Results: Curcumin showed a dose-and time-dependent effects on cell viability on 4T1 cells, as well as increasing PAR4 expression. Compared with the control group (phosphate-buffered saline), mice treated with curcumin showed an increase in plasma PAR4. In the Balb/C tumor model, mice treated with curcumin and cisplatin showed greater tumor shrinkage than the control group. Conclusion: These results indicate that curcumin induces expression of soluble PAR4 and sensitizes tumor cells to cisplatin.Prostate apoptosis response 4 (PAR4) is a tumor-suppressor gene that induces apoptosis via extracellular and intracellular mechanisms in cancer cells without affecting normal cells (1, 2). Its expression is decreased in some neoplasms, and it is associated with a poor prognosis (3, 4). In breast cancer, metastasis, resistance, and recurrence require PAR4 dysregulation (5-7). Recently, PAR4 has been observed to be secreted spontaneously in normal cell culture and not in cancer cells by various agents that induce endoplasmic reticulum stress in both mice and humans; this increases cellular secretion of PAR4 via a P53-dependent mechanism (5,8,9). Chloroquine and hydroxychloroquine are antimalarial drugs that act as robust secretagogues of PAR4 (5). On the other hand, arylquinoline 1 disrupts the integration between PAR4-vimentin, increasing its secretion (9, 10). Through the extracellular interaction with glucoseregulated protein 78 (GRP78), which is overexpressed on the surface of cancer cells and is correlated with malignancy, soluble PAR4 causes extrinsic apoptosis via FAS-associated death domain/caspase 8 and caspase 3 pathways in various 2767

ntroducción. Las muertes en los pacientes con cáncer de mama ocurren principalmente por la recurrencia y metástasis y no por el tumor primario, la agresividad del tumor se asocia al estatus hormonal, tumores receptor estrógeno negativo o triple negativo son neoplasias de mal pronóstico que tienen la capacidad de inducir metástasis o recurrencia la baja expresión de Par-4 se asocia a un mal pronóstico, por esa razón analizamos la participación de Par-4 en la recurrencia tumoral. Área cubierta. Se realizo una búsqueda de artículos relacionades con cáncer de mama, recurrencia y Par-4 en el PubMed y en otros bancos de datos, con la finalidad de comprender la relación de Par-4 como gen supresor de tumor con el proceso carcinogénico y recurrencia de cáncer de mama. Opinión experta. La baja expresión Par-4 está asociado en tumores receptor de estrógeno negativo o con alto grado de transformación, la expresión de par-4 disminuye o es bloqueada en las células remantes después de la quimioterapia y durante el proceso de transición epitelial mesenquimal (EMT) en la recurrencia del tumor, observándose que ar-4 es necesaria y esencial para la recurrencia del cáncer de mama. El entendimiento de la biología del Par-4 en el cáncer de mama abre la posibilidad de ser empleado como una estrategia terapéutica para que coadyuven a la eliminación destrucción de los tumores resistentes o recurrentes de cáncer de mama.