Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT-20 cells.

Drug options for the life-threatening Cushing's disease are limited, and surgical resection or radiation therapy is not invariably effective. Testicular receptor 4 (TR4) has been identified as a novel drug target to treat Cushing's disease. We built the structure model of TR4 and searched the TR4 antagonist candidate via in silico virtual screening. Bexarotene was identified as an antagonist of TR4 that can directly interact with TR4 ligand binding domain (TR4-LBD) and induces a conformational change in the secondary structure of TR4-LBD. Bexarotene suppressed AtT-20 cell growth, proopiomelanocortin (POMC) expression and adrenocorticotropin (ACTH) secretion. Mechanism dissection revealed that bexarotene could suppress TR4-increased POMC expression via promoting the TR4 translocation from the nucleus to the cytoplasm. This TR4 translocation might then result in reducing the TR4 binding to the TR4 response element (TR4RE) on the 5' promoter region of POMC. Results from in vivo mouse model also revealed that oral bexarotene administration markedly suppressed ACTH-secreting tumour growth, adrenal enlargement and the secretion of ACTH and corticosterone in mice with already established tumours. Together, these results suggest that bexarotene may be developed as a potential novel therapeutic drug to better suppress Cushing's disease.

A Competing Endogenous RNA Network and an 8-lncRNA Prognostic Signature Identify MYO16-AS1 as an Oncogenic lncRNA in Bladder Cancer.

Recently, growing evidence has shed light on the competitive endogenous RNAs (ceRNAs) activity of long noncoding RNAs (lncRNAs) in carcinogenesis and tumor progression. To better elucidate the regulatory mechanisms of lncRNA in muscle-invasive bladder cancer (MIBC), we identified aberrantly expressed mRNAs, lncRNAs, and miRNAs in tumor tissues by using RNA sequence profiles from The Cancer Genome Atlas. The MIBC-specific ceRNA network, including 58 lncRNAs, 22 miRNAs, and 52 mRNAs, was constructed and visualized in Cytoscape. Further, using the univariate and multivariate Cox regression model, we screened 8 lncRNAs (AC078778.1, LINC00525, AC008676.1, AP000553.1, SACS-AS1, AC009065.1, AC127496.3, and MYO16-AS1) to construct an lncRNA signature for predicting the overall survival of MIBC patients. Kaplan-Meier analysis and a receiver operating characteristic curve were applied to evaluate the performance of the signature. Real-time quantitative PCR analysis was carried out to test expression levels of the 8 lncRNAs in MIBC patient tissues. Transwell assays demonstrated that overexpressing MYO16-AS1 can enhance UMUC2 migration and invasion. Our study offers a novel lncRNA-correlated ceRNA model to better understand the molecular mechanisms involved in MIBC. In addition, we developed an independent 8-lncRNAs biomarker for prognostic prediction and identified MYO16-AS1 as an oncogenic lncRNA in bladder cancer.

Transcription Factor HBP1 Enhances Radiosensitivity by Inducing Apoptosis in Prostate Cancer Cell Lines.

Radiotherapy for prostate cancer has been gradually carried out in recent years; however, acquired radioresistance often occurred in some patients after radiotherapy. HBP1 (HMG-box transcription factor 1) is a transcriptional inhibitor which could inhibit the expression of dozens of oncogenes. In our previous study, we showed that the expression level of HBP1 was closely related to prostate cancer metastasis and prognosis, but the relationship between HBP1 and radioresistance for prostate cancer is largely unknown. In this study, the clinical data of patients with prostate cancer was compared, and the positive correlation was revealed between prostate cancer brachytherapy efficacy and the expression level of HBP1 gene. Through research on prostate cancer cells in vitro, we found that HBP1 expression levels were negatively correlated with oncogene expression levels. Furthermore, HBP1 overexpression could sensitize prostate cancer cells to radiation and increase apoptosis in prostate cancer cells. In addition, animal model was employed to analyze the relationship between HBP1 gene and prostate cancer radiosensitivity in vivo; the result showed that knockdown of HBP1 gene could decrease the sensitivity to radiation of xenograft. These studies identified a specific molecular mechanism underlying prostate cancer radiosensitivity, which suggested HBP1 as a novel target in prostate cancer radiotherapy.

Early channel transurethral resection of the prostate for patients with urinary retention after brachytherapy.

OBJECTIVE: It is recommended that transurethral resection of the prostate (TURP) after brachytherapy should not be performed at an early stage after implantation. Herein we report our experiences and the results of channel TURP (cTURP) within six months post-implant for patients with refractory urinary retention. METHODS: One hundred and ninety patients with localized prostate cancer of clinical stages T1c to T2c were treated by brachytherapy as monotherapy at our institution from February 2009 to July 2013. Nine patients who developed refractory urinary retention and underwent cTURP within six months after brachytherapy were retrospectively reviewed and analyzed. RESULTS: The median interval between prostate brachytherapy and cTURP was three months (range 1.5 to 5.0 months). There were no intraoperative or postoperative complications and no incontinence resulting from the surgery. All urinary retention was relieved per the American Brachytherapy Society urinary symptom score. With a mean follow-up time of 16 months (range 6 to 26 months) after cTURP, no patient experienced biochemical recurrence. The mean serum prostate-specific antigen (PSA) of the patients who underwent cTURP was 0.42 ng/ml (range 0.08 to 0.83 ng/ml) at the end of their follow-up. CONCLUSIONS: Early cTURP was found to be safe and effective in relieving urinary retention after brachytherapy and could be performed without compromising its therapeutic efficacy.

Metachronous contralateral testicular and bilateral adrenal metastasis of chromophobe renal cell carcinoma: a case report and review of the literature.

Chromophobe renal cell carcinoma (ChRCC) metastatic to the testis has not, to the best of our knowledge, been reported in the literature. Nor have there been reports of delayed bilateral adrenal metastasis of ChRCC. Here we report a case of metachronous contralateral testicular and bilateral adrenal metastasis of ChRCC in a 70-year-old man who underwent right radical nephrectomy for RCC six years ago. He was admitted to the hospital because of left intrascrotal enlargement of two-month duration. Ultrasonography revealed a mass in the upper pole of the left testis. Computed tomography (CT) showed irregular masses in the bilateral adrenal area. Left radical orchiectomy and laparoscopic bilateral adrenalectomy were performed. The pathologic examination showed metastatic ChRCC in the left testis and bilateral adrenal gland. Postoperative follow-up showed that the patient had survived for at least 56 months without recurrence. The case highlights the unique behavior of RCC with an unusual site of metastasis and favorable survival after multiple metastasectomy.