Three-dimensional-printed soft kidney model for surgical simulation of robot-assisted partial nephrectomy: A proof-of-concept study.

n/

PAX2 promoted prostate cancer cell invasion through transcriptional regulation of HGF in an in vitro model

AbstractElucidating the mechanism of prostate cancer cell invasion may lead to the identification of novel therapeutic strategies for its treatment. Paired box 2 (PAX2) and hepatocyte growth factor (HGF) proteins are promoters of prostate cancer cell invasion. We found that PAX2 protein activated the HGF gene promoter through histone H3 acetylation and upregulated HGF gene expression. Deletion analysis revealed that the region from −637 to −314 of the HGF gene was indispensable for HGF promoter activation by PAX2. This region contains consensus PAX2 binding sequences and mutations of the sequences attenuated HGF promoter activation. Using an in vitro invasion model, we found that PAX2 and HGF promoted prostate cancer cell invasion in the same pathway. Knockdown of HGF expression attenuated the cells' invasive capacity. Moreover, in tissue samples of human prostate cancers, HGF and PAX2 expression levels were positively correlated. These results suggested that upregulation of HGF gene expression by PAX2 enhanced the invasive properties of prostate cancer cells. The PAX2/HGF pathway in prostate cancer cells may be a novel therapeutic target in prostate cancer patients

Treatment impact of newly approved therapeutic agents for metastatic urothelial carcinoma in Japan: a single-center retrospective study

Abstract Although recent clinical trials of new therapeutic agents for metastatic urothelial carcinoma have shown prolonged overall survival, there are few real-world evidence. To assess the impact of new therapeutic agents, we performed retrospective analysis for consecutive 158 metastatic urothelial carcinoma patients who performed systemic therapy in our institution between May 2008 and August 2023. We defined a period from May 2008 to December 2017, when pembrolizumab was first introduced to the clinical setting in the new therapeutic agents for metastatic urothelial carcinoma in Japan, as “pre new drug era” and a period from January 2018 to August 2023 as “post new drug era”. We compared overall survival between pre- and post- new drug era using Kaplan–Meier method with log rank test. Median overall survival of pre- and post- new drug era were 14.5 months (95% confidence intervals: 11.6–16.7) and 23.1 months (95% confidence intervals: 14.5-NA), respectively (p < 0.001). Five-year survival rate of pre- and post- new drug era was 7.0% (95% confidence intervals: 2.3–15.3) and 36.3% (95% confidence intervals: 21.4–51.5), respectively. Multivariable Cox proportional hazards regression analysis of factors associated with overall survival showed that enfortumab vedotin administration, administration of second-line or more systemic therapy, best overall response of SD, PR and CR in first-line systemic therapy, higher serum albumin and lower CRP were factors for overall survival prolongation. Introduction of new therapeutic agents for metastatic urothelial carcinoma contributed to the improvement of overall survival in comparison with the era without these agents

Bilateral Pheochromocytoma with Germline MAX Variant without Family History

Recently, the genetic background of pheochromocytomas/paragangliomas (PPGLs) has been rapidly revealed. These tumors have been referred to as the “ten percent tumor”; however, the frequency of genetic variants of PPGLs has turned out to be more common than expected. PPGLs are potentially hereditary tumors and appear clinically sporadic. Here, we report a case of bilateral pheochromocytoma (PCC) with a variant in the MYC-associated factor X (MAX) gene (c.295 + 1G > A). A male patient was diagnosed with adrenal pheochromocytoma (PCC) and underwent a left adrenalectomy at the age of 40. A new tumor in the right adrenal gland was detected at the age of 43. Urinary metanephrine and normetanephrine concentrations gradually increased. The size of the right adrenal PCC continued to increase one year after detection. Genetic testing of the peripheral blood revealed the presence of a pathogenic variant in MAX. The natural history of adrenal PCCs with the MAX variant has not yet been clarified, because the number of reported cases is not sufficient. Thus, clinicians should consider a MAX variant when they find bilateral or multiple PCCs