Utilizing databases to study the expression of DLG5 in clear cell renal cell carcinoma and its prognostic significance / 西安交通大学学报(医学版)

Objective: To clarify the role of discs large homolog 5 (DLG5) in the diagnosis and prognosis of renal clear cell carcinoma (ccRCC) by studying the expression of DLG5 in the clinical tissue of ccRCC. Methods: DLG5 expression in ccRCC tissues and normal renal tissue was measured by using the Cancer Genome Atlas (TCGA) Database and Gene Expression Omnibus (GEO) Database. The correlation of DLG5 expression with the prognosis and clinicopathological parameters of ccRCC was analyzed by LinkedOmics and GEPIA. The interactions protein network of DLG5 was predicted by String-DB. Results: Compared with that of the normal kidney tissues, DLG5 expression was significantly upregulated in the ccRCC tissues (P<0.05). The high DLG5 expression was an independent prognostic factor affecting the overall survival rate of ccRCC based on TCGA (P=2.997×10-5). Furthermore, DLG5 expression had a positive correlation with the TNM stage, ethnicity, tumor purity, year-to-birth, PCNA (P=1.1×10-6, R=0.19), and RAD1 (P=5.7×10-6, R=0.18) expression of ccRCC. Conclusion: In ccRCC, the high expression of DLG5 is a significant index of poor prognosis. Therefore, DLG5 can be a potential biomarker for predicting the metastasis, recurrence and prognosis of the patients.

The expression of IFN-γ and FOXP3 in the microenvironment of renal cell cancer, and its role in the tumor infiltrating lymphocytes distribution / 中华泌尿外科杂志

Objective To investigate the role of IFN-γ and FOXP3 expression in subpopulation distribution and functions of tumor-infiltrating lymphocytes (TILs) in the microenvironment of renal cell cancer.Methods 30 renal cell cancer tissue samples were freshly collected from the laparoscopic radical nephrectomy in the first hospital of Jiaxing.After frozen sectioning,immunofluorescent staining was conducted to detect the infiltrating CD4 positive and CDs positive cells,and the expression of FOXP3 and IFN-γ as well.In addition,TILs were isolated from the tumor tissues by density-gradient centrifugation.TILs from tumor center or tumor invasive edge were purified independently and measured for the mRNA levels of FOXP3 and IFN-γ by qRT (quantitative reverse transcription)-PCR.Results Tumor-infiltrating CD4+ and CD8+ T cells were concentrated in the invasive edge of renal cell cancer tissues.The expression of FOXP3 was found to be inversely related to that of IFN-γ from the immunofluorescent staining.The relative FOXP3 mRNA levels for the TILs from tumor center and invasive edge were 64.6 ± 9.4 and 36.2 ± 1.8,respectively,with significant difference(P ＜0.05).The relative IFN-γ mRNA levels were 631.8 ± 151.4 and 1 726.0 ± 344.1 (P ＜ 0.05).The trend of relative expression of FOXP3 was reversed in terms of IFN-γ.Conclusions The study on the renal cell cancer tissue samples suggested that the tumor-specific cytotoxic immune cells relatively concentrated in the tumor invasive edge.

miR-206 inhibits renal cell cancer growth by targeting GAK / 华中科技大学学报（医学）（英德文版）

Renal cell cancer (RCC) remains one of the most lethal types of cancer in adults. MicroRNAs (miRNAs) play key roles in the pathogenesis of RCC. The role of miR-206 in RCC has not been fully understood. The purpose of this study was to examine the role of miR-206 in the regulation of proliferation and metastasis of RCC and the possible mechanism. miR-206 expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in RCC cell lines (786-O and OS-RC-2 cells) and clinical samples. MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] method, colony formation and transwell assay were used to detect the tumor-suppressing ability of miR-206 in RCC. Luciferase assay was performed to verify the precise target of miR-206. The results showed that the expression of miR-206 was significantly down-regulated in RCC tissues and cells. The expression level of cyclin G-associated kinase (GAK), a master regulator of tumor proliferation and metastasis, was up-regulated with the decrease in miR-206 in RCC tissues as well as RCC cell lines. In addition, the miR-206 inhibitor promoted the proliferation, migration and invasion of 786-O and OS-RC-2 cells. Bioinformatics combined with luciferase and Western blot assays revealed that miR-206 inhibited the expression of GAK. Moreover, miR-206 regulates RCC cell growth partly through targeting GAK. Our study indicated that miR-206 functions as a tumor suppressor in regulating the proliferation, migration and invasion of RCC by directly targeting GAK, and it holds promises as a potential therapeutic target for RCC.

miRNA-30a expression in renal cell carcinoma and its effect on renal cancer cells / 中国肿瘤临床

Objective:To investigate the expression and clinical significance of microRNA-30a in renal cell carcinoma (RCC). Methods:The miRNA-30a expression in renal tissues and cell lines was detected using quantitative real-time polymerase chain reac-tion (qRT-PCR), and the relationship between miRNA-30a expression and the clinicopathological features of RCC was analyzed. The effect of miRNA-30a on cancer cells was evaluated using methyl thiazolyl tetrazolium (MTT) assay. In addition, a bioinformatics algo-rithm was adopted to predict the potential targets of miRNA-30a. Results:miRNA-30a was downregulated both in RCC tissues and cell lines. Patients with higher miRNA-30a expression exhibited better prognosis than those with lower miRNA-30a expression. Bioin-formatics algorithm and qRT-PCR both indicated that metadherin (MTDH) was a target of miRNA-30a. Moreover, MTT results showed that miRNA-30a could inhibit cell proliferation. Conclusion:miRNA-30a was inhibited in renal cancer, and low miRNA-30a expres-sion was associated with poor prognosis. In addition, miRNA-30a could inhibit the growth of cells through MTDH.

Sunitinib in metastatic renal cell carcimoma: A single-center experience.

INTRODUCTION: Historically, metastatic renal cell carcinoma (RCC) has had poor prognosis; the outcomes have improved with the introduction of tyrosine‑kinase inhibitors, such as sunitinib. There is no reported literature from India on the use of sunitinib in metastatic RCC. We present an analysis of sunitinib at our institute over 4 years. MATERIALS AND METHODS: An unselected population of patients with metastatic or relapsed metastatic RCC receiving sunitinib was analyzed with respect to patient characteristics, response, toxicity, and outcomes. RESULTS: Fifty‑nine patients (51 males, 8 females) with a median age of 55 years were included in the study. Lungs and bones were the most common site of metastases. The patients received a median number of 4 cycles, with 23 patients requiring dose‑modification and 12 discontinuing therapy due to toxicity. Overall, 38 patients (65%) had CR, PR, or standard deviation while 14 had progression or death at initial evaluation. The median progression‑free survival (PFS) was 11.4 months and overall survival was 22.6 months. Hand–foot syndrome, fatigue, mucositis, skin rash, and vomiting were seen more often among our patients, whereas hypertension was not as common compared with previously published reports. CONCLUSION: Sunitinib is a viable option for the treatment of metastatic RCC and shows a comparable PFS in Indian patients. Although toxicity remains a concern, most of the adverse effects can be managed conservatively. Careful patient selection, tailoring the dose of therapy, adequate counseling, and careful follow‑up is essential for optimum therapy.

The Usefulness of Stereotactic Radiosurgery for Radioresistant Brain Metastases

OBJECTIVE: We investigated the effectiveness of stereotactic gamma knife Radiosurgery (GKR) for radioresistant brain metastases with the impact upon histology. METHODS: Between April 2004 and May 2011, a total of 23 patients underwent GKR for 67 metastatic brain tumors from 12 renal cell cancers, 5 sarcomas and 6 melanomas. The mean age was 56 years (range, 18 to 79 years). Most of the patients were classified as the Radiation Therapy Oncology Group recursive partitioning analysis class II (91.3%). The synchronous metastasis was found in 6 patients (26.1%) and metachronous metastasis in 17 patients (73.9%). We analyzed the local control rate, intracranial progression-free survival (PFS) and overall survival (OS). RESULTS: The mean tumor volume for GKR was 2.24 cc and the mean prescription dose was 19.4 Gy (range, 10 to 24) to the tumor margin. Out of metachronous metastases, the median duration to intracranial metastasis was 3.3 years in renal cell cancer (RCC), 2.4 years in melanoma and 1.1 years in sarcoma (p=0.012). The total local control rate was 89.6% during the mean 12.4 months follow-up. The six-month and one-year local control rate was 90.2% and 83% respectively. Depending on the pathology, the control rate of RCC was 95.7%, sarcoma 91.3% and melanoma 80.5% during the follow-up. The common cause of local failure was the tumor bleeding in melanoma. The median PFS and OS were 5.2 and 8.4 months in RCC patients, 6.5 and 9.8 months in sarcoma, and 3.8 and 5.1 months in melanoma. CONCLUSION: The GKR can be one of the effective management options for the intracranial metastatic tumors from the radioresistant tumors. The melanoma showed a poor local control rate compared to other pathologies because of the hemorrhage.

Risk factors of renal artery pseudoaneurysm following partial nephrectomy / 中华泌尿外科杂志

ObjectiveTo study the risk factors of renal artery pseudoaneurysm (RAP) following partial nephrectomy.MethodsOpen partial nephrectomy was performed on a total of 464 cases of renal cell cancer from July 2003 to May 2010. Five patients ( 1.1％ ) had postoperative hemorrhage from RAP.The surgery technique of the open partial nephrectomy, the clinical presentation, imaging findings and treatment of RAP were reviewed. The anatomical characteristics of these five renal tumors on enhanced CT were quantified using the R.E.N.A.L. Nephrometry Score System.ResultsAll five cases were male, two had tumors on the left side and three on the right side. Median tumor size was 3.6 cm ( range from 2.5 to 5 cm; Radius score 1 - 2). Four tumors were exophytic of these, three had a major endophytic component (≥50％) deep in the parenchyma (Exophytic/endophytic score 2 ), one was entirely endophytic (score 3 ). The distance of all the tumors to the collecting system was ≤4 mm ( Nearness score 3 ). Four of the five tumors were across the polar line and/or renal axial midline ( Location score 3 ). The other tumor was located under the lower pole ( Location score 1 ) but close to the renal hilar. All patients presented with delayed gross haematuria and decreasing hemoglobin occurred on mean postoperative day 12 (3 -23 day). Four patients complained of flank pain, two of which had signs of hypovolemia requiring blood transfusion. The diagnosis was confirmed by the contrast medium-enhanced CT and selective angiography, and RAP was found most commonly arising from the segmental branch of renal artery. Superselective microcoil angioembolization was successfully performed in four cases, once in three cases and twice in the remaining case. The procedure failed in one patient and a nephrectomy was done. At a mean follow-up of 21 months (12 -30) , all patients had normal renal function without evidence of recurrence.ConclusionsRAP should be considered in all patients who had delayed hematuria after partial nephrectomy. A central, deep tumor and its relationship to the segmental branch of renal artery could be an important risk factor for this complication. Choosing the case properly for partial nephrectomy and suturing the transected vessels and the defect of parenchymal correctly could reduce occurrence of this serious complication. Early use of selective angioembolization could be a primary choice of treatment.

Effects of HIF-2? and VEGF on Angiogenesis and Metastasis of Renal Cell Carcinoma / 中国医师杂志

Objective To explore the expression of HIF-2? and VEGF in renal cell carcinoma (RCC) and their correlation with angiogenesis and metastasis of renal cell carcinoma. Methods Expression of HIF-2? and VEGF were assessed by immunohistochemical straining in 48 cases of renal cell carcinomas. Results In 48 cases of renal cell carcinomas, positive rate of HIF-2? was 70.8%. Strong expression of HIF-2? was observed in 12 cases, moderate in 10 cases, weak in 12 cases and no expression in 14cases.There was a significant difference in HIF-2? expression between carcinoma tissues and control tissues (P

Prostate Specific Membrane Antigen Expression in Renal Cell Carcinoma and Transitional Cell Carcinoma / 대한비뇨기과학회지

PURPOSE: Prostate specific membrane antigen (PSMA) has been used in molecular staging of prostatic cancer and known as a more sensitive marker than PSA (prostate specific antigen). Recently it has been known that PSMA is expressed in various tissue including kidney, bladder, testis, duodenum, breast, colon, etc. We performed RT-PCR (reverse transcriptase-polymerase chain reaction) assay for PSMA to evalute whether PSMA is expressed in renal cell carcinoma and bladder transitional cell carcinoma or not. MATERIALS AND METHODS: RNA was extracted from renal cell carcinoma cell lines (Caki-1, Caki-2, 7860, A498, ACHN, and 769-P), peripheral blood of metastatic renal cell carcinoma patients (7), peripheral blood of metastatic bladder transitional cell carcinoma patients (8), normal urothelium, bladder transitional cell carcinoma cell lines (RT4, 5637, HT1376, T24, TccSup) and prostatic cancer cell lines (LNCaP, DuCaP). These RNAs were analyzed by nested RT-PCR assay for the expression of PSMA. 196 bp nested PCR product was excised from the gel, cloned, and sequenced. RESULTS: PSMA mRNA was expressed in Caki-1, peripheral blood of metastatic renal cell ca (4/7, P=0.006), peripheral blood of metastatic blader trnasitional cell carcinoma patient (3/8, P=0.032), HT1376, LNCaP, and DuCaP. Automated sequencing analysis showed that all sequences were identical with PSMA mRNA sequence. CONCLUSIONS: PSMA is expressed in renal cell carcinoma and bladder transitional cell carcinoma besides prostatic cancer. This result suggests the possibility that PSMA expression can be a new biomarker for the renal cell carcinoma and bladder transitional cell carcinoma.

Renal cell carcinoma protocol

This paper presents some important concepts on renal cancer. Renal cancers origin, incidence, etiology, pathogenesis, histology, clinical presentation, manifestations due to tumor thrombus, manifestations secondary to metastasis, laboratory findings, tumor makers, diagnostic examinations, and differential diagnosis are discussed. The treatment protocol for renal cell carcinoma, from stages I-IV, are also included