Gongxian Wang

Long-Term Results of a Prospective, Randomized Trial Comparing Retroperitoneoscopic Partial Versus Total Adrenalectomy for Aldosterone Producing Adenoma

PURPOSE The indication for laparoscopic total or partial adrenalectomy in patients with aldosterone producing adrenal adenoma remains controversial. We compared retroperitoneoscopic partial and total adrenalectomy for aldosterone producing adrenal adenoma in a prospective, randomized, multicenter trial. MATERIALS AND METHODS Patients with aldosterone producing adrenal adenoma were randomized to retroperitoneoscopic partial or total adrenalectomy. Patient characteristics, surgical data, complications and postoperative clinical results were analyzed statistically. RESULTS From July 2000 to March 2004, 212 patients were enrolled in this study, including 108 and 104 who underwent total and partial adrenalectomy, respectively. The 2 groups were comparable in patient age, gender, body mass index and tumor site. Mean followup was 96 months in each group. No conversion to open surgery was needed and no major complications developed. Partial adrenalectomy required a shorter operative time than total adrenalectomy but this did not attain statistical significance. Intraoperative blood loss in the partial adrenalectomy group was significant higher than in the total adrenalectomy group (p <0.05) but no patient needed blood transfusion. All patients in each group showed improvement in hypertension, and in all plasma renin activity and aldosterone returned to normal after surgery. No patient required potassium supplements postoperatively. In the total and partial adrenalectomy groups 32 (29.6%) and 29 patients (27.9%), respectively, were prescribed a decreased dose of or fewer antihypertensive medicines at final followup. CONCLUSIONS Retroperitoneoscopic partial adrenalectomy is technically safe. It has therapeutic results similar to those of total adrenalectomy in patients with primary aldosteronism due to aldosteronoma.

Survivin and PSMA Loaded Dendritic Cell Vaccine for the Treatment of Prostate Cancer

Dendritic cell (DC)-based vaccines are a promising therapeutic modality for cancer. Results from recent trials and approval of the first DC vaccine by the U.S. Food and Drugs Administration for prostate cancer have paved the way for DC-based vaccines. A total of 21 hormone refractory prostate cancer (HRPC) patients with a life expectancy >3 months were randomised into two groups. DC loaded with recombinant Prostate Specific Membrane Antigen (rPSMA) and recombinant Survivin (rSurvivin) peptides was administered as an subcutaneous (s.c.) injection (5×10(6) cells). Docetaxel (75 mg/m(2) intravenous (i.v.)) and prednisone (5 mg, bis in die (b.i.d.)) served as control. Clinical and immunological responses were evaluated. Primary endpoints were safety and feasibility; secondary endpoint was overall survival. Responses were evaluated on day 15, day 30, day 60, and day 90. DC vaccination was well tolerated with no signs of grade 2 toxicity. DC vaccination induced delayed-type hypersensitivity reactivity and an immune response in all patients. Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumours (RECIST) was 72.7% (8/11) versus 45.4 (5/11) in the docetaxel arm and immune related response criteria (irRC) was 54.5% (6/11) compared with 27.2% (3/11) in the control arm. The DC arm showed stable disease (SD) in 6 patients, progressive disease (PD) in 3 patients, and partial remission (PR) in two patients compared to SD in 5 patients, PD in 6 patients, and PR in none in the docetaxel arm. There was a cellular response, disease stabilization, no adverse events, and partial remission with the rPSMA and rSurvivin primed DC vaccine.

MiR-221-induced PUMA silencing mediates immune evasion of bladder cancer cells.

Immune evasion of cancer cells is mainly due to the impaired transduction of apoptotic signals from immune cells to cancer cells, as well as inhibition of subsequent apoptosis signal cascades within the cancer cells. Over the past few decades, the research has focused more on the impaired transduction of the apoptotic signal from immune cells to cancer cells, rather than inhibition of the intracellular signaling pathways. In this study, miR‑221 inhibitor was transfected into bladder cancer cell lines 5637, J82 and T24 to repress the expression of miR‑221. As a result, the repression of miR‑221 on p53 upregulated modulator of apoptosis (PUMA) was abolished, resulting in increased expression of the pro-apoptotic Bax and reduced expression of the anti-apoptotic Bcl-2, which promotes apoptosis of bladder cancer cells. The expression of MMP-2, MMP-9 and VEGF-C were reduced, resulting in reduced invasiveness and infiltration capability of bladder cancer cells, thereby inhibiting the immune evasion of bladder cancer cells.

Dissecting the roles of the androgen receptor in prostate cancer from molecular perspectives

Androgen receptor plays a pivotal role in prostate cancer progression, and androgen deprivation therapy to intercept androgen receptor signal pathway is an indispensable treatment for most advanced prostate cancer patients to delay cancer progression. However, the emerging of castration-resistant prostate cancer reminds us the alteration of androgen receptor, which includes androgen receptor mutation, the formation of androgen receptor variants, and androgen receptor distribution in cancer cells. In this review, we introduce the process of androgen receptor and also its variants’ formation, translocation, and function alteration by protein modification or interaction with other pathways. We dissect the roles of androgen receptor in prostate cancer from molecular perspective to provide clues for battling prostate cancer, especially castration-resistant prostate cancer.

Enhanced antitumor activity of epirubicin combined with cerulenin in osteosarcoma

Osteosarcoma (OS) is the most common primary malignant neoplasm in children and adolescents. Epirubicin is one of the chemotherapeutic agents currently used for the treatment of OS; however, the efficacy of chemotherapy is hampered by the acquired drug resistance of OS. Cerulenin, an inhibitor of fatty acid synthase, has been defined as a candidate tumor suppressor. In this study, we explored the combined effect of cerulenin plus the chemotherapy drug, epirubicin, on human OS U2-OS cells in vitro and in vivo. We demonstrated that cerulenin plus epirubicin induced synergistic growth inhibition and enhanced apoptosis in U2-OS cells. We also demonstrated that cerulenin plus epirubicin synergistically suppressed tumor growth in subcutaneously xenografted U2-OS cells in athymic nude mice. Our results indicate that cerulenin enhances the anti-OS effects of epirubicin in vivo and in vitro.

Do histological variants in urothelial carcinoma of the bladder portend poor prognosis? A systematic review and meta-analysis

The clinical implications of histological variants in urothelial carcinoma of the bladder has been a subject of significant controversy with many unanswered questions that remain. To clarify whether histological variants presage poor prognosis for patients suffering from urothelial carcinoma of the bladder, we scoured through various electronic databases such as Medline, Web of Knowledge, and the Cochrane Library up to August 18, 2016. Experts were consulted, and references from relevant articles were scanned. We identified thirteen eligible studies which met the inclusion criteria, including 9,533 participants. The existing evidence indicates that histological variants in urothelial carcinoma of the bladder patients do not alter their prognosis.

A comprehensive analysis of cancer-driving mutations and genes in kidney cancer

An accumulation of driver mutations is important for cancer formation and progression, and leads to the disruption of genes and signaling pathways. The identification of driver mutations and genes has been the subject of numerous previous studies. The present study was performed to identify cancer-driving mutations and genes in renal cell carcinoma (RCC), prioritizing noncoding variants with a high functional impact, in order to analyze the most informative features. Sorting Intolerant From Tolerant (SIFT), Polymorphism Phenotyping version 2 (Polyphen2) and MutationAssessor were applied to predict deleterious mutations in the coding genome. OncodriveFM and OncodriveCLUST were used to detect potential driver genes and signaling pathways. The functional impact of noncoding variants was evaluated using Combined Annotation Dependent Depletion, FunSeq2 and Genome-Wide Annotation of Variants. Noncoding features were analyzed with respect to their enrichment of high-scoring variants. A total of 1,327 coding mutations in clear cell RCC, 258 in chromophobe RCC and 1,186 in papillary RCC were predicted to be deleterious by all three of MutationAssessor, Polyphen2 and SIFT. In total, 77 genes were positively selected by OncodriveFM and 1 by OncodriveCLUST, 45 of which were recurrently mutated genes. In addition, 10 signaling pathways were recurrently mutated and had a high functional impact bias (FM bias), and 31 novel signaling pathways with high FM bias were identified. Furthermore, noncoding regulatory features and conserved regions contained numerous high-scoring variants, and expression, replication time, GC content and recombination rate were positively correlated with the densities of high-scoring variants. In conclusion, the present study identified a list of cancer-driving genes and signaling pathways, features like regulatory elements, conserved regions, replication time, expression, GC content and recombination rate are major factors that affect the distribution of high-scoring non-coding mutations in kidney cancer.

γ‑secretase inhibitor inhibits bladder cancer cell drug resistance and invasion by reducing epithelial‑mesenchymal transition

A previous study by our group demonstrated that the expression levels of Notch 1 and Jagged 1 in bladder cancer cells was significantly lower compared with those in normal bladder mucosa, while the expression levels of Notch 1 and Jagged 1 in invasive bladder cancer were higher compared with those in superficial bladder cancer. The present study investigated the effect of the Notch signaling pathway on the drug resistance and invasiveness of bladder cancer cells. It was demonstrated that complete inhibition of the Notch signaling pathway induced significant morphological changes and inhibited cell proliferation and migration (P<0.05). Reverse transcription quantitative polymerase chain reaction and western blot analyses revealed that the mRNA and protein expression levels of E-cadherin were upregulated (P<0.05) and the mRNA and protein expression levels of N-cadherin, vimentin and α-smooth muscle actin were downregulated (P<0.05). The present study concluded that complete inhibition of the Notch signaling pathway inhibited cell proliferation and invasion, and reduced drug resistance in bladder cancer cells, a phenomenon which may be associated with the inhibition of the epithelial-mesenchymal transition.

MP37-07 THE ADRENAL SCORE: A COMPREHENSIVE SCORING SYSTEM FOR STANDARDIZED EVALUATION OF ADRENAL MASS

INTRODUCTION AND OBJECTIVES: Treatment planning for adrenal tumors depends on a variety of qualitative and quantitative data, including tumor nature and anatomy, as well as the experience of the operating surgeon. Here, we have developed and propose a scoring system for adrenal masses designated as the A.D.R.E.N.A.L Score, to quantify the nature and anatomical characteristics of adrenal masses based on endocrinological assessment, computerized tomography and patient habitus. METHODS: The A.D.R.E.N.A.L score consists of 7 components including (A)ldosterone/cortisol/catecholamine secretion or suspicion of malignancy based on endocrinological and radiological study, (D)imension (tumor size as the maximal diameter), (R)elationship to adjacent organs, (E)nhancement on computerized tomography, (N)earness of the tumor to major vessels, (A)dipose (patient habitus as body mass index), and a combination of two (L)ocation descriptors [anterior (a) or posterior (p), left (L) or right (R)]. The A.D.R.E.N.A.L score was applied to 345 cases, including 212 laparoscopic retroperitoneal adrenalectomy cases and 105 robotic retroperitoneal adrenalectomy cases and 28 robotic transperitoneal adrenalectomy cases. RESULTS: For all three series, the A.D.R.E.N.A.L score accurately classified the complexity of cases in the above three series as evidenced by the positive correlation between the A.D.R.E.N.A.L score and surgical outcomes including the operative time and estimated blood loss, while BMI or tumor size did not as independent risk factor. CONCLUSIONS: Standardized evaluation of an adrenal tumor is essential for individualized patient preparation, surgical planning and postoperative care which translate to patient safety and cost-effectiveness. The A.D.R.E.N.A.L score is a reproducible classification system based on endocrinological, oncological and anatomical characteristics of adrenal masses. This novel scoring system of adrenal masses may provide a common reference for the decision making of both endocrinologist and urologist, assessment of the surgical risks, patient safetyguided designing of adrenalectomy training programs, and stratified analysis and comparisons of adrenal surgeries within a single or among multiple institutions.