Immunotherapy Based on Tumor Microenvironment in Renal Cell Carcinoma / 中国医学科学院学报

Renal cell carcinoma (RCC) is a common lethal urological cancer,the distant metastasis of which is the leading cause of death.Although targeted agents have remarkably improved the overall prognosis of RCC patients,nearly all the patients eventually acquire therapeutic resistance.With the advent of immune checkpoint inhibitors,immunotherapy based on tumor microenvironment (TME) has shown a broad scope in clinical application.The deepening understanding of TME leads to the changes of therapeutic strategies for advanced RCC,and the combination of targeted therapy and immunotherapy is exhibiting a promising prospect.Herein,we reviewed the TME characteristics,candidate predictive biomarkers,and possible targets for future development of drugs against RCC.

CMTM2 is involved in spermiogenesis in mice / 北京大学学报(医学版)

OBJECTIVE@#To investigate whether CKLF-like MARVEL transmembrane domain-containing protein 2 (CMTM2) is involved in spermatogenesis in mice. CMTM2 is highly expressed in testis, and could possibly be a potential spermagogenesis specific gene.@*METHODS@#CMTM2-deficient mouse model was generated. Northern, RT-PCR and Western blotting analysis were performed on total RNA derived from wild-type (WT, CMTM2+/+) and CMTM2+/- (heterozygote) and CMTM2-/-(homozygote) mice to examine the CMTM2 level. The number of litters and the number of pups were counted and pregnancy rates calculated. The motility and morphology of the sperm and the histology of testes were analyzed. Serum testosterone and FSH concentrations were also measured. Standard t-tests were used and standard error of means were calculated.@*RESULTS@#CMTM2 was highly expressed in a finely regulated pattern in the mouse testis during spermatogenesis. The body weight of adult mice with CMTM2 deficiency was not significantly different from that of wild type mice. No obvious anatomical or behavioral abnormalities were observed. The testis of CMTM2-/- was smaller than that of CMTM2+/+ mice. The testis diameter in wild mice and CMTM2 null mice were (11.32±1.21) mm vs. (8.29±1.92) mm (P<0.05), and the weights were (101.63±2.33) mg vs. (85.22±2.84) mg (P<0.05), respectively. Female CMTM2 null mice were fertile, indicating that CMTM2 was not required for female gametogenesis. The CMTM2-/- mice produced virtually no sperm, and CMTM2+/- mice sperm count showed a significant decline. In terms of sperm morphorlogy study, more round spermatids could be observed in the heterozygote group, compared with the wild type group; while in the homozygote group, a large amount of round spermatids could be observed because of complete arrest of spermiogenesis. The hormone levels were not significantly different. The CMTM2-/- male mice were sterile due to a late, complete arrest of spermiogenesis. The organized architecture of the seminiferous epithelium of the seminiferous tubules seen in CMTM2+/+ mice was lost in CMTM2-/- mice.@*CONCLUSION@#This study suggests CMTM2 is not required for embryonic development in the mouse but is essential for spermiogenesis, however, further studies are required for more detailed mechanism study.

Minimal fat renalangiomyolipoma with multiple lymph nodes enlargement and postoperative refractory lymphatic fistula: a case report and literature review / 北京大学学报(医学版)

Renal angiomyolipoma (AML) is a common benign tumor in the urinary system, mainly composed of adipose tissue, blood vessels and muscle tissue. Renal AML is sporadic in most of patients, while a few are associated with tuberous sclerosis. Classical renal AML occurs predominantly in middle-aged females. Most cases are found incidentally during imaging examinations. The fat content makes AML have unique imaging characteristics and is easy to be identified with other renal tumors. However, the amount of fat varies in each tumor. AML that contains only microscopically detectable fat and whose amount of intratumoral fat may be too small to be identified on unenhanced computed tomography (CT) images is termed minimal fat or fat-poor renal AML, which appears as a high density shadow in the renal parenchyma on unenhanced CT images. Thus, it can be difficult to distinguish it from renal cell carcinoma (RCC) on imaging. Since the imaging findings are atypical, the diagnosis depends on pathological results. In addition, a few of AML can mimic malignant neoplasms. Recent studies suggested that AML might involve to peri-renal or renal sinus fat, regional lymphatics and other visceral organs, as well as inferior vena cava, which further makes the diagnosis more difficult. However, there is currently no reports about involvement of regional limphatics in minimal fat renal AML. In this article, we report a 27-year-old female patient without family history of tuberous sclerosis, who came to visit the hematologist because a high density shadow near the left kidney was found during CT scan which was accompanied by neck, armpits, groin, abdominal cavity and retroperitoneal lymph nodes enlargement. She was suspected of lymphoma in the beginning and transferred to Department of Urology to perform laparoscopic left renal mass and retroperitoneal lymph node excision and pathological examination for a definitive diagnosis. Finally, pathologic results revealed AML. Postoperative continuous lymphatic fistula developed and the retroperitoneal drainage of chylous fluid was 100-200 mL per day, lasting for 12 weeks. The fistula was successfully closed after conservative treatment including fasting and rehydration. This article summaries and discusses the diagnosis and treatment of renal AML with lymph nodes enlargement and the management of postoperative refractory lymphatic fistula by reviewing the related cases and literature.

Influence of SOX10 on the proliferation and invasion of prostate cancer cells / 北京大学学报(医学版)

OBJECTIVE@#To explore the influence of SOX10 on the proliferation and invasion of prostate cancer cells.@*METHODS@#SOX10 protein in prostate cancer cell lines PC3, DU145 and LNcap was detected by Western blotting analysis. The expression of SOX10 in prostate cancer cell lines (PC3 and DU145) were knocked down by small interfering RNAs, and the efficiency of SOX10 by small interfering RNAs was confirmed using Western blotting analysis. CCK-8 assays were conducted to assess the influences of SOX10 on the proliferation of PC3 and DU145 cells, and invasion assays were conducted to assess the influences of SOX10 on the invasion of PC3 and DU145 cells.@*RESULTS@#After SOX10 in prostate cancer cells was knocked down by small interfering RNAs, the proliferation of prostate cancer cells PC3 and DU145 was significantly inhibited. Results of CCK-8 assays showed that the absorbance of PC3 and DU145 in SOX10-silenced groups was decreased compared with those in control groups (PC3: 0 d: 0.166±0.01, 0.162±0.012 vs. 0.155 ±0.01, P>0.05; 1 d: 0.210±0.011, 0.211±0.018 vs. 0.252±0.023, P>0.05; 2 d: 0.293±0.017, 0.280±0.028 vs. 0.433±0.030, P<0.01; 3 d: 0.363±0.071, 0.411±0.038 vs. 0.754±0.045, P<0.01; 4 d: 0.592±0.065, 0.670±0.093 vs. 1.456±0.111, P<0.01. DU145: 0 d: 0.168±0.018, 0.164±0.01 vs. 0.153 ±0.012, P>0.05; 1 d: 0.218±0.007, 0.206±0.024 vs. 0.255±0.02, P>0.05; 2 d: 0.297±0.013, 0.291±0.012 vs. 0.444±0.023, P<0.05; 3 d: 0.378±0.058, 0.419±0.026 vs. 0.762±0.039, P<0.01; 4 d: 0.681±0.094, 0.618±0.050 vs. 1.419±0.170, P<0.01). Meanwhile, knocking down SOX10 significantly suppressed the invasion of prostate cancer cells PC3 and DU145. Results of invasion assays showed that the numbers of invaded cells in SOX10-silenced groups were significantly less than those in control groups (PC3: 142±38, 171±17 vs. 304±55; DU145: 96±22, 134±23 vs. 341±34, P<0.05).@*CONCLUSION@#SOX10 might promote prostate cancer progression by accelerating the ability of the proliferation and invasion of prostate cancer cells, and SOX10 might be a potential therapeutic target for prostate cancer.