No abstract

Testicular germ cell tumor (TGCT) is a rare cancer but the most common tumor among adolescent and young adult males. Patients with advanced TGCT often exhibit a worse prognosis due to the acquisition of therapeutic resistance. Cisplatin-based chemotherapy is a standard treatment for advanced TGCTs initially sensitive to cisplatin, as exemplified by embryonal carcinoma. The acquisition of cisplatin resistance, however, could be a fatal obstacle for TGCT management. To identify cisplatin resistance-related genes, we performed transcriptome analysis for cisplatin-resistant TGCT cells compared to parental cells. In two types of cisplatin-resistant TGCT cell models that we established from patient-derived TGCT cells, and from the NEC8 cell line, we found that mRNA levels of the high-mobility-group nucleosome-binding gene HMGN5 and meiosis-related gene TEX11 were remarkably upregulated compared to those in the corresponding parental cells. We showed that either HMGN5 or TEX11 knockdown substantially reduced the viability of cisplatin-resistant TGCT cells in the presence of cisplatin. Notably, TEX11 silencing in cisplatin-resistant TGCT cells increased the level of cleaved PARP1 protein, and the percentage of double-strand break marker γH2AX-positive cells. We further demonstrated the therapeutic efficiency of TEX11-specific siRNA on in vivo xenograft models derived from cisplatin-resistant patient-derived TGCT cells. Taken together, the present study provides a potential insight into a mechanism of cisplatin resistance via TEX11-dependent pathways that inhibit apoptosis and DNA damage. We expect that our findings can be applied to the improvement of cisplatin-based chemotherapy for TGCT, particularly for TEX11-overexpressing tumor.

BackgroundAcquired therapeutic resistance and metastasis/recurrence remain significant challenge in advance renal cell carcinoma (RCC), thus the establishment of patient-derived cancer models may provide a clue to assess the problem. We recently characterized that neuritogenesis-related protein neuritin 1 (NRN1) functions as an oncogene in testicular germ cell tumor. This study aims to elucidate the role of NRN1 in RCC.MethodsNRN1 expression in clinical RCC specimens was analyzed based on immunohistochemistry. NRN1-associated genes in RCC were screened by the RNA-sequencing dataset from The Cancer Genome Atlas (TCGA). RCC patient-derived cancer cell (RCC-PDC) spheroid cultures were established and their viabilities were evaluated under the condition of gene silencing/overexpression. The therapeutic effect of NRN1-specific siRNA was evaluated in RCC-PDC xenograft models.ResultsNRN1 immunoreactivity was positively associated with shorter overall survival in RCC patients. In TCGA RCC RNA-sequencing dataset, C-X-C chemokine receptor type 4 (CXCR4), a prognostic and stemness-related factor in RCC, is a gene whose expression is substantially correlated with NRN1 expression. Gain- and loss-of-function studies in RCC-PDC spheroid cultures revealed that NRN1 significantly promotes cell viability along with the upregulation of CXCR4. The NRN1-specific siRNA injection significantly suppressed the proliferation of RCC-PDC-derived xenograft tumors, in which CXCR4 expression is significantly repressed.ConclusionNRN1 can be a potential diagnostic and therapeutic target in RCC as analyzed by preclinical patient-derived cancer models and clinicopathological studies.

We report 2 rare cases of intrascrotal tumors complicated acute scrotum. Case 1: A 15-year-old adolescent presented to our emergency room with acute right scrotal pain. Testicular torsion was suspected, and surgical exploration was performed. A spermatocele with 180 degrees torsion on its pedicle was observed. The patient was diagnosed with torsion of a spermatocele, and it was excised. Case 2: A 25-year-old man presented with acute left scrotal pain. Testicular torsion was suspected, and manual detorsion relieved the pain effectively. However, scrotal swelling did not subside after detorsion, and surgical exploration was performed. The left testis was stony hard on palpation, and intraoperative ultrasound revealed a mosaic echo pattern. A testicular tumor was highly suspected and left high orchiectomy was performed. Histopathological examination revealed seminoma pT1. Torsion of a testicular tumor was diagnosed. Although these 2 cases are extremely rare, they should be considered for the differential diagnosis of acute scrotum.