Hongchao He

Sorafenib or sunitinib as postoperative adjuvant therapy for Chinese patients with locally advanced clear cell renal cell carcinoma at high risk for disease recurrence.

OBJECTIVE To evaluate the efficacy and safety of targeted agents (sorafenib and sunitinib) as postoperative adjuvant therapy in Chinese patients with clear cell renal cell carcinoma (CC-RCC) who are at high risk for disease recurrence. MATERIALS AND METHODS Forty-three patients treated at our center between December 2007 and December 2010 with locally advanced CC-RCC who were at a high risk for disease recurrence were enrolled into the study. The criteria for high risk of CC-RCC recurrence postoperatively were defined according to the Mayo Clinic stage, size, grade, and necrosis (SSIGN) score for CC-RCC. After radical nephrectomy, patients received either sorafenib (group A, n = 20) or sunitinib (group B, n = 23) and were followed up for at least 1 year to determine the efficacy and safety of the test products. The duration of maintenance targeted medication treatment was approximately 1 year. Group C consisted of 388 CC-RCC patients treated at our center between 1992 and 2007, who were at high risk for disease recurrence and who received no adjuvant therapy. RESULTS The demography characteristics were similar among the 3 groups. The overall rate of recurrence in groups A and B was not different (15.0% and 17.4% (P > 0.05), respectively), which was lower than that of group C (38.7%, P < 0.05 compared with groups A and B). Disease-free survival (DFS) was longer in groups A and B (18.9 ± 5.9 months and 16.9 ± 6.1 months [P > 0.05], respectively), compared with group C (13.3 ± 7.2 months, P < 0.05 compared with groups A and B). The common adverse effects of targeted therapy included hand-foot syndrome, fatigue, diarrhea, taste disturbance, rash, hypertension, alopecia, stomatitis, neutropenia, nausea, pruritus, hypothyroidism in groups A and B. The adverse effects were mild in both groups and the incidence was not significantly different between groups A and B. CONCLUSIONS Targeted adjuvant therapy postoperatively with sorafenib or sunitinib in patients with CC-RCC who are at a high risk for disease recurrence was well tolerated and effective in reducing the rate of CC-RCC recurrence in these patients. This study is an attempt to assess the utility of adjuvant tyrosine kinase inhibitors (TKIs) after surgery for renal carcinoma. The apparently improved outcomes, compared with a historical control population, are of sufficient interest to support the continuation of an ongoing randomized clinical trial to validate the hypothesis.

Heparanase-1 and Cyclooxygenase-2: prognostic indicators of malignancy in pheochromocytomas

The objective of this article is to evaluate Heparanase-1 and Cyclooxygenase-2 as tissue-based markers of pheochromocytoma prognosis. Ninety-two sporadic pheochromocytoma patients with a minimum of 8-year follow-up post-diagnosis were enrolled. Slides of normal adrenal glands in nephrectomy specimens from 20 patients with benign renal tumors were as control. Heparanase-1 and Cyclooxygenase-2 expression as well as microvessel density were examined using immunohistochemistry in tissues from these patients. Positive staining for Heparanase-1 was observed in 23.68% of the benign and 77.78% of the malignant cases, whereas none of the normal adrenal controls showed positive staining. Similarly, Cyclooxygenase-2 staining was seen in 23.68% of the benign versus 83.33% of the malignant cases, and none of the normal controls appeared positive for Cyclooxygenase-2. Using both HPA-1 and Cox-2 combined, the positive predictive value of malignancy was significantly increased to 0.72, compared to about 0.45 by their own. Malignant cases showed higher microvessel density compared to benign tumors and normal controls (36.41, 21.43, and 13.36%, respectively). Heparanase-1 and Cyclooxygenase-2 may contribute to the invasive characteristics of malignant pheochromocytomas. Heparanase-1 and Cyclooxygenase-2 combined is better than their own to be used as a marker to distinguish malignant from benign pheochromocytoma.

Tension-free vaginal tape retropubic sling for recurrent stress urinary incontinence after Burch colposuspension failure.

Objectives:  To verify the efficacy and to clarify the mechanism of the tension‐free vaginal tape retropubic sling for recurrent stress urinary incontinence after Burch colposuspension failure.

The Advantages of Unilateral Pedal Lymphography in the Diagnosis of Chyluria

Objectives: To evaluate the efficacy and safety of pedal lymphography (PLG) in the localization diagnosis of chyluria. Methods: Cystoscopy was performed in 153 patients and PLG in 121 cases. Unilateral or staged bilateral ligation and stripping of renal lymphatic vessel were performed according to the results of cystoscopy and/or PLG. Results: Unilateral and bilateral urinary excretion of chyle was detected in 123 and 1 case by cystoscopy, respectively. In 121 cases receiving PLG, 100 cases of unilateral fistulous connection between the renal pelvis and the lymphatic system, 18 cases of bilateral fistulas and 1 case of lymphatic bladder fistula were demonstrated. PLG has a higher diagnostic rate for the detection of bilateral lymphatic renal pelvis fistulas than cystoscopy (p < 0.05). 28 cases received renal pedicle lymphatic disconnection only according to the results of cystoscopy, and 3 of them failed (10.1%). While 121 cases had the same operation according to the results of PLG, only 1 case failed the operation (0.8%). Conclusions: PLG was efficient and safe for the localization diagnosis of chyluria, with a higher detection rate of bilateral fistulas than cystoscopy. PLG might benefit the selection of appropriate therapy and improve the surgical effect.

Specific inhibition of ICAM-1 effectively reduces bladder inflammation in a rat model of severe non-bacterial cystitis

The development and progression of bladder pain syndrome/interstitial cystitis (BPS/IC) is closely related to bladder inflammation. Intercellular adhesion molecule 1 (ICAM-1) is associated with bladder inflammation in BPS/IC. We investigated the effect of specific inhibition of ICAM-1 using an anti-ICAM-1 antibody (AIA) on bladder inflammation in a rat model of severe non-bacterial cystitis (NBC) resembling BPS/IC by evaluating the bladder inflammation grade, mast cell infiltration and related cytokines and receptors. We also compared the effects of AIA with the COX-2 inhibitor celecoxib and the neurokinin-1 receptor (NK1R) inhibitor aprepitant. Our NBC model was established by intraperitoneal injection of cyclophosphamide combined with intravesical protamine/lipopolysaccharide, which resulted in severe bladder inflammation and increased mast cell infiltration, similar to the pathological changes of BPS/IC. Inhibition of ICAM-1 by AIA significantly decreased the bladder inflammation grade and mast cell counts, which was accompanied by a reduction of purinergic receptors (P2X2/P2X3), prostaglandin E2, EP1/EP2 receptors, TNF-α, NK1R, and ICAM-1. Moreover, AIA showed superior effects to those of celecoxib and aprepitant treatment in improving the bladder inflammatory response. Our results suggest that ICAM-1 may play a critical role in bladder inflammation in severe NBC and may be used as a novel therapeutic target in non-bacterial bladder inflammation such as BPS/IC.

Right-Crossed, Fused Renal Ectopia L-Shaped Kidney Type with Urinary Chyluria

Crossed fused renal ectopia combined with chyluria is extremely rare. Here we report the case of a patient who was admitted to our institution since milky urine and was finally found to have an L-shaped fused kidney and renal pelvis fistula. The patient was cured by renal pelvic instillation sclerotherapy.

Fbxw7 regulates renal cell carcinoma migration and invasion via suppression of the epithelial-mesenchymal transition

F-box and WD repeat domain containing 7 (Fbxw7) is an F-box protein that belongs to the SKP1-CUL1-F-box protein E3 ligase complex and is responsible for transferring the ubiquitin molecule to the substrate, which results in its recognition and subsequent degradation by proteasomes. Furthermore, it can identify a network of signaling proteins that function in cell growth, diversion and apoptosis. In the present study, Fbxw7 was downregulated in renal cell carcinoma (RCC) tissues compared with the adjacent non-tumor tissues and its expression was significantly associated with the tumor-node-metastasis stage, lymph node metastasis and distant metastasis in patients with RCC. Furthermore, multivariate Cox regression analyses indicated that Fbxw7 expression was an independent factor for the prediction of the overall survival of patients with RCC. A functional study demonstrated that downregulation of Fbxw7 facilitated tumor cell migration and invasion via the epithelial-mesenchymal transition (EMT). Therefore, the results of the current study indicted that Fbxw7 is an anti-oncogene that serves a notable function in RCC development by suppressing RCC metastasis and the EMT, indicating the potential therapeutic value of Fbxw7 in inhibiting metastasis in RCC.

Study on the mechanism behind lncRNA MEG3 affecting clear cell renal cell carcinoma by regulating miR-7/RASL11B signaling: HE et al.

The goal of this research was to study the relationships between maternally expressed gene 3 (MEG3), microRNA‐7 (miR‐7), and RASL11B, and explore their influence on the progression of clear cell renal cell carcinoma (CCRCC). Microarray analysis was conducted using the data provided by The Cancer Genome Atlas. The expression levels of MEG3 and miR‐7 in CCRCC and adjacent tissue samples were ascertained by quantitative real‐time polymerase chain reaction (qRT‐PCR). The cell proliferation activity was unmasked by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, and cell apoptosis and cell cycle were investigated by flow cytometry. A dual luciferase reporter assay was used to verify target relationships. Wound healing assay and transwell assay were used to detect cell migration and invasion ability. Decreased MEG3 expression was observed in CCRCC tissues and cells. Overexpression of MEG3 accelerated apoptosis; inhibited cell proliferation, migration and invasion; and induced G0/G1 phase cell cycle arrest in CCRCC. MiR‐7, directly binding to MEG3, was overexpressed in the CCRCC tissues and could inhibit the apoptosis and promote the migration and invasion of CCRCC cells. RASL11B, lowly expressed in CCRCC, was a target of miR‐7. After the overexpression of RASL11B, G0/G1 phase cell cycle arrest was induced; cell apoptosis was promoted; and the proliferation, invasion, and migration of CCRCC cells were inhibited. MEG3 could up‐regulate RASL11B to inhibit the cell proliferation, invasion, and migration; induce G0/G1 cell cycle arrest; and promote cell apoptosis by suppressing miR‐7 in CCRCC.

Silencing of MED27 inhibits adrenal cortical carcinogenesis by targeting the Wnt/β-catenin signaling pathway and the epithelial-mesenchymal transition process

Abstract This study aimed to explore the effect of MED27 on the expression of epithelial-mesenchymal transition (EMT)-related proteins and β-catenin in adrenal cortical carcinoma (ACC). The functional mechanism of MED27 on ACC processes was also explored. The expression of MED27 was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). siRNA was utilized to knockdown the expression of MED27. CCK8 assays were performed to evaluate SW-13 cell proliferation. Transwell assays were performed to assess the invasion ability, and wound healing assays were utilized to detect migration. A tumor xenograft mouse model was established to investigate the impact of silencing MED27 on tumor growth and metastasis. MED27 was highly expressed in ACC tissues and cells. Down-regulation of MED27 induced ACC cell apoptosis, and significantly attenuated ACC cell proliferation, invasion and metastasis in vivo and in vitro. MED27 knockdown regulated the expression of EMT-related proteins and Wnt/β-catenin signaling pathway-related proteins. Our study investigated the function and mechanism of MED27 and validated that MED27 plays a negative role in ACC occurrence and progression and could be utilized as a new therapeutic target in ACC prevention and treatment.

Targeting of CCN2 suppresses tumor progression and improves chemo-sensitivity in urothelial bladder cancer

Urothelial bladder cancer (UBC) is the most common urinary neoplasm in China. CCN family protein 2 (CCN2), a cysteine-rich matricellular protein, is abnormally expressed in several cancer types and involved in tumor progression or chemo-resistance. However, detailed expression patterns and effects of CCN2 in UBC still remain unknown. We found that down-regulation of CCN2 suppressed proliferation, migration and invasion of UBC cells in vitro and targeting of CCN2 decelerated xenograft growth in vivo. When treated with mitomycin C (MMC), CCN2-scilencing UBC cells showed lower survival and higher apoptotic rates and these effects were probably mediated via inactivation of Akt and Erk pathways. We also demonstrated the clinical significance of CCN2 expression, which was higher in UBC tissues and associated with advanced tumor stage and high pathologic grade. Taken together, our data suggest that CCN2 is an oncogene in UBC and might serve as a matricellular target for improving chemotherapeutic efficacy.