記述言語：英語   掲載種別：研究論文（学術雑誌）  

Advanced bladder cancer (BC) (local invasive and/or metastatic) is not curable even with cytotoxic chemotherapy, immune checkpoint inhibitors, and targeted treatment. Targeting GSK-3β is a promising novel approach in advanced BC. The induction of autophagy is a mechanism of secondary resistance to various anticancer treatments. Our objectives are to investigate the synergistic effects of GSK-3β in combination with autophagy inhibitors to evade GSK-3β drug resistance. Small molecule GSK-3β inhibitors and GSK-3β knockdown using siRNA promote the expression of autophagy-related proteins. We further investigated that GSK-3β inhibition induced the nucleus translocation of transcription factor EB (TFEB). Compared to the GSK-3β inhibition alone, its combination with chloroquine (an autophagy inhibitor) significantly reduced BC cell growth. These results suggest that targeting autophagy potentiates GSK-3β inhibition-induced apoptosis and retarded proliferation in BC cells.

DOI： 10.3390/curroncol30060406

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Sarcomatoid carcinoma is a rare, high-grade malignancy with epithelial and mesenchymal components. It may be a good candidate for immunotherapy because it is associated with overexpression of programmed cell death ligand 1. Sarcomatoid urothelial carcinoma (UC) of the upper urinary tract is extremely rare. Here we report the first case of sarcomatoid UC of the renal pelvis that responded to immunotherapy. CASE PRESENTATION: A 79-year-old man was referred to our hospital complaining of various symptoms, including anorexia and abdominal pain. A computed tomography scan revealed a right atrial tumor, a 9 cm left renal mass with a renal vein tumor thrombus, para-aortic lymphadenopathy, and multiple small lung nodules. The patient underwent resection of the right atrial tumor. Pathological analysis of the tumor did not lead to an accurate diagnosis even after several rounds of immunohistochemistry. He underwent a needle biopsy of the left kidney and was initially diagnosed with collecting duct carcinoma, a rare subtype of renal cell carcinoma (RCC). Following the initial diagnosis, immunotherapy with nivolumab and ipilimumab commenced. Thereafter, almost all lesions, including the left renal tumor, were reduced in size. However, he underwent a left nephrectomy approximately a year after beginning immunotherapy due to repeated left renal bleeding. Histological examination of the nephrectomy specimen revealed two forms of cancer-sarcomatoid UC and conventional high-grade UC. Two months after surgery, the patient was found to have new lung metastases. He underwent chemotherapy with gemcitabine and cisplatin, followed by immunotherapy with pembrolizumab. However, both treatments were ineffective. The patient died of cancer 19 months after his first admission. CONCLUSIONS: The presented case of sarcomatoid UC of the renal pelvis that partially responded to immunotherapy suggests that immunotherapy can be a promising treatment for sarcomatoid UC.

DOI： 10.1186/s12894-023-01210-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Immune checkpoint inhibitors (ICI) have dramatically changed the treatment of metastatic renal cell carcinoma (mRCC). Although many studies have reported biomarkers as predicting the efficacy of ICI in mRCC, they remain controversial and have challenges to apply in real-world practice. We evaluated prognostic significance of multiple molecules associated with tumor immunity in patients treated with ICI. The molecules were detected in tumor tissues by immunohistochemical staining. We identified CD8-positive T cells and CD68-positive macrophages infiltrating into the tumor tissue as significant favorable prognostic factors for ICI treatment. Conversely, high expression of CD4-positive T cells was associated with poor response to ICI. Furthermore, we demonstrated that scoring for the expression status of these three molecules provides a remarkably accurate biomarker in patients with mRCC. Even the classical approach of immunohistochemistry could predict the outcome of ICI treatment by assessing the combined status of tumor-infiltrating immune cells.

DOI： 10.1038/s41598-022-24437-6

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記述言語：英語  

Introduction: Tumors in the fibroma-thecoma group are benign tumors, typically found in the ovaries of postmenopausal women and occasionally develop in the testes. These tumors are mostly treated with radical orchiectomy because preoperative diagnosis confirming the benign nature is difficult. Case presentation: A 40-year-old man was incidentally pointed out to have a right intrascrotal mass, measuring approximately 10 cm on computed tomography. Malignant testicular tumor was suspected based on the location and size of the tumor. The patient underwent right radical orchiectomy. Histologically, the tumor had no evidence of malignancy, and the diagnosis of tumors in the fibroma-thecoma group was made. The patient had no recurrence 8 months after surgery. Conclusion: Intrascrotal tumors in the fibroma-thecoma group are rare benign tumors and mostly treated with radical orchiectomy due to concerns about malignancies. Further investigation is needed for accurate preoperative diagnosis, and we should be aware of these rare tumors.

DOI： 10.1002/iju5.12430

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The selection of effective therapeutic agents is critical for improving the survival of patients with renal cell carcinoma (RCC). The aim of the present study was to develop an ex vivo drug testing assay using patient‑derived tumor organoid (TO) cultures. For this purpose, surgical tumor specimens were obtained from 20 patients with RCC. TOs were developed ex vivo from freshly resected RCC tumors, and their histopathological and molecular characteristics were evaluated using histological staining and whole‑exome sequencing (WES). Using a cell viability assay, the therapeutic efficacy of standard of care tyrosine kinase inhibitors in RCC TOs was determined. It was found that TOs recapitulated the histological features of primary RCC tumors. Using WES, a strong concordance was identified at the genetic level between the primary tumors and their corresponding TOs. Using patient‑derived TO models, a prototype of an ex vivo drug testing assay was developed, and it was found that RCC TOs exhibited differential responses to sunitinib, pazopanib, cabozantinib, axitinib and sorafenib treatment. On the whole, although the predictive value of the current assay has to be tested and validated in future clinical studies, the findings of the present study demonstrate a novel approach for ex vivo drug testing in patient‑derived TO models, which may have potential for use in the personalized treatment of cancer patients.

DOI： 10.3892/or.2021.8177

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記述言語：日本語   出版者・発行元：日本尿路結石症学会  

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記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会総会事務局  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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