[Predicting the 3-year tumor-specific survival in patients with T3a non-metastatic renal cell carcinoma].

OBJECTIVE: To predict the 3-year cancer-specific survival (CSS) of patients with non-metastatic T3a renal cell carcinoma after surgery. METHODS: A total of 336 patients with pathologically confirmed T3a N0-1M0 renal cell carcinoma (RCC) who underwent surgical treatment at the Department of Urology, Peking University Third Hospital from March 2013 to February 2021 were retrospectively collected. The patients were randomly divided into a training cohort of 268 cases and an internal validation cohort of 68 cases at an 4 ∶ 1 ratio. Using two-way Lasso regression, variables were selected to construct a nomogram for predicting the 3-year cancer-specific survival (CSS) of the patients with T3aN0-1M0 RCC. Performance assessment of the nomogram included evaluation of discrimination and calibration ability, as well as clinical utility using measures such as the concordance index (C-index), time-dependent area under the receiver operating characteristic curve [time-dependent area under the curve (AUC)], calibration curve, and decision curve analysis (DCA). Risk stratification was determined based on the nomogram scores, and Kaplan-Meier survival analysis and Log-rank tests were employed to compare progression-free survival (PFS) and cancer-specific survival (CSS) among the patients in the different risk groups. RESULTS: Based on the Lasso regression screening results, the nomogram was constructed with five variables: tumor maximum diameter, histological grading, sarcomatoid differentiation, T3a feature, and lymph node metastasis. The baseline data of the training and validation sets showed no statistical differences (P>0.05). The consistency indices of the column diagram were found to be 0.808 (0.708- 0.907) and 0.903 (0.838-0.969) for the training and internal validation sets, respectively. The AUC values for 3-year cancer-specific survival were 0.843 (0.725-0.961) and 0.923 (0.844-1.002) for the two sets. Calibration curves of both sets demonstrated a high level of consistency between the actual CSS and predicted probability. The decision curve analysis (DCA) curves indicated that the column diagram had a favorable net benefit in clinical practice. A total of 336 patients were included in the study, with 35 cancer-specific deaths and 69 postoperative recurrences. According to the line chart, the patients were divided into low-risk group (scoring 0-117) and high-risk group (scoring 119-284). Within the low-risk group, there were 16 tumor-specific deaths out of 282 cases and 36 postoperative recurrences out of 282 cases. In the high-risk group, there were 19 tumor-specific deaths out of 54 cases and 33 post-operative recurrences out of 54 cases. There were significant differences in progression-free survival (PFS) and cancer-specific survival (CSS) between the low-risk and high-risk groups (P < 0.000 1). CONCLUSION: A nomogram model predicting the 3-year CSS of non-metastatic T3a renal cell carcinoma patients was successfully constructed and validated in this study. This nomogram can assist clinicians in accurately assessing the long-term prognosis of such patients.

[Functional and oncologic outcomes of partial nephrectomy for cystic renal cell carcinoma: A single-center retrospective study].

OBJECTIVE: To investigate the postoperative renal function and oncologic outcomes of cystic renal cell carcinoma with partial nephrectomy, and to compared the single-center data on surgical outcomes with the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: This was a retrospective study that included the patients with cystic renal cell carcinoma who underwent partial nephrectomy in the Department of Urology, Peking University Third Hospital (PUTH) from 2010 to 2023. The clinical data and depicting baseline characteristics were collected. Renal dynamic imaging and the Chinese Coefficients for Chronic Kidney Disease Epidemiology Collaboration (C-CKD-EPI) formulae were used to calculate the estimated glomerular filtration rate (eGFR). The renal function curves over time were then plotted, and the patients were followed-up to record their survival status. Cases of cystic renal cell carcinoma in the SEER database between 2000 and 2020 were included, propensity score matching (PSM) was performed to balance the differences between SEER cohort and PUTH cohort, and the cancer-specific survival (CSS) curves for both groups were plotted and statistical differences were calculated by the Kaplan-Meier method. RESULTS: A total of 38 and 385 patients were included in the PUTH cohort and SEER cohort, respectively, and 31 and 72 patients were screened in each cohort after PSM. Of the baseline characteristics, only tumor size (P=0.042) was found to differ statistically between the two groups. There was no statistically significant difference between the two cohorts in terms of CSS after PSM (P=0.556). The median follow-up time in the SEER cohort was 112.5 (65, 152) months and a 10-year survival rate of 97.2%, while the PUTH cohort had a median follow-up of 57.0 (20, 1 172) months and a 10-year survival rate of 100.0%. There was no statistically significant difference between eGFR determined by preoperative renal dynamic imaging and the results of the C-CKD-EPI formulae based on creatinine estimation (P=0.073). There was a statistically significant difference in eGFR among the preoperative, short-term postoperative, and long-term postoperative (P < 0.001), which was characterized by the presence of a decline in renal function in the short-term postoperative period and the recovery of renal function in the long-term period. CONCLUSION: Partial nephrectomy for cystic renal cell carcinoma is safe and feasible with favorable renal function and oncologic outcomes.

Renal Angiomyolipoma with Tumor Thrombus in the Inferior Vena Cava and Right Atrium Accompanied by Renal Cell Carcinoma: A Case Report.

Background: Renal angiomyolipoma (AML) without local invasion is generally considered benign. However, it may extend to the renal sinus, even the renal vein, or the inferior vena cava (IVC). In patients with non-tuberous sclerosis complex, coexistence of renal cell carcinoma (RCC) and renal AML is uncommon. Case presentation: A 72-year-old woman was incidentally found to have a solitary right renal mass with an IVC thrombus extending into the right atrium during a routine health checkup. Robot-assisted laparoscopic radical nephrectomy and thrombectomy were successfully performed through adequate preoperative examination and preparation. Two tumor lesions were found and pathologically confirmed as renal AML and RCC, and the tumor thrombus was derived from the renal AML. During the one-year follow-up period, no signs of recurrence or metastatic disease were observed. Conclusions: Renal AML with a tumor thrombus in the IVC and right atrium accompanied by RCC may occur, although rarely. In clinical practice, if preoperative manifestations differ from those of common diseases, rare diseases must be considered to avoid missed diagnoses. In addition, adequate examination and multidisciplinary discussions before making a diagnosis are necessary. For a level 4 tumor thrombus with no infringement of the venous wall, adoption of robot-assisted minimally invasive surgery, without extracorporeal circulation technology, is feasible.

Preoperative predictive model of early urinary continence recovery after laparoscopic radical prostatectomy.

PURPOSE: To develop and validate a predictive model include magnetic resonance imaging (MRI) parameters preoperatively which can assess the risk of incontinence after laparoscopic radical prostatectomy (LRP) accurately. METHODS: We retrospectively reviewed and included 170 patients with prostate cancer who underwent LRP between July 2015 and June 2018 in our institution. All 170 patients were randomly resampled and divided into training set (n = 124) and verification set (n = 46) according to the ratio of 7:3. The Nomogram prediction model of the risk of incontinence after LRP was established through the training set and verified by the verification set. Baseline patient characteristics were obtained, including age, body mass index, and prostate volume. Perioperative characteristics such as pre-biopsy prostate specific antigen, biopsy Gleason score, clinical staging, and NVB sparing status were also collected. MRI parameters preoperatively including membranous urethral length (MUL), prostate apex depth ratio (PADR), and intravesical prostatic protrusion length (IPPL) were obtained. The C index and visual inspection of calibration curve were used to evaluate the discrimination and calibration of the model. RESULTS: According to the urinary incontinence (UI) at 3 months postoperatively, the patients were divided into 104 cases (61.2%) in the group with no incontinence and 66 patients (38.8%) in the group with incontinence. Multivariate logistic regression analysis of training set showed that cT3a (OR = 0.427, 95% CI 0.142-1.281, P = 0.1288), MUL (OR = 0.237, 95% CI 0.102-0.551, P < 0.01), PADR (OR = 0.276, 95% CI 0.116-0.655, P < 0.01), and IPPL (OR = 0.073, 95% CI 0.030-0.179, P < 0.01) were independent predictors of urinary incontinence at 3 months postoperatively. The model showed good discrimination with an area under the receiver operating characteristic (ROC) curve of 0.880, with the sensitivity and specificity 0.800 and 0.816, respectively, and good calibration (Hosmer-Lemeshow test result of 5.57, P = 0.695). Decision curve analysis demonstrated that the model was clinically useful. CONCLUSION: This study developed and validated a preoperative model in the form of a nomogram to predict the risk of UI after LRP at 3 months. MUL, PADR, and IPPL were significant independent predictive factors of the postoperative early urinary continence.

'Seven-step two-lobe' HoLEP: a modification to gain efficiency of the enucleation applying relatively low-power holmium laser devices.

PURPOSE: In order to increase the efficiency of the low-power holmium laser enucleation of the prostate (LP-HoLEP), and introduce it as a standard surgery for BPH, we described a modified 'seven-step two-lobe' HoLEP (ST HoLEP) technique applying 60-W device in a stepwise manner. METHODS: From July 2016 to August 2019, 120 patients who received LP-HoLEP at our hospital because of urinary tract symptoms caused by BPH were included in the study. The patients were assigned into two groups, 60 consecutive patients received modified ST HoLEP compared with another preexisting 60 consecutive patients who received the conventional three-lobe HoLEP (T HoLEP) before the technical modification. The clinical parameters, including patient characteristics, perioperative data, as well as voiding outcomes, and complications were evaluated after at least 3-month follow-up. RESULTS: The median enucleation efficiency of the ST HoLEP was 0.72 gm/min, which was significantly higher than 0.62 gm/min of the T HoLEP. Despite the preoperative IPSS was slightly higher in T HoLEP group, the other preoperative and perioperative data showed no statistical difference between the two groups. After ST HoLEP procedure, the urinary incontinence rate was continually improved at 1-week, 1-month, and 3-month follow-up which were 13.3%, 6.7%, and 1.7%, respectively. There was no significant difference in postoperative voiding outcomes and urinary continence results in 3-month follow-up. CONCLUSION: The ST HoLEP technique was proved to increase the efficiency which was benefit from minimizing the surgical incision, facilitating the single surgical plane identification and maintenance during the whole enucleation procedure.

[Management of calyceal diverticular calculi with stenotic infundibulum by flexible ureteroscopic holmium laser infundibulectomy and lithotripsy].

OBJECTIVE: To evaluate the efficacy and safety of flexible ureteroscopic holmium laser lithotripsy in treating calyceal diverticular calculi with stenotic infundibulum and to present our initial experience. METHODS: From Nov. 2012 to Nov. 2014, 10 patients with stone-bearing calyceal diverticulum and stenotic infundibulum underwent flexible ureteroscopic holmium laser lithotripsy in our hospital, including 3 female patients and 7 male patients with an average age of 36.9 years (range: 20 to 62 years). There were 6 patients with right side while 4 patients with left side calyceal diverticular calculi. The average cumulative stone size was (1.33±0.43) cm. Five patients underwent extracorporeal shock wave lithotripsy (ESWL) before hospital admission but no stone was discharged. All the patients received intravenous urography (IVU) and CT-urography (CTU) preoperatively and underwent double-J stents placement 2 weeks before operations. A digital-fiber flexible ureteroscopy and 200 µm holmium laser fiber were used for treatment. Surgeries began with routine flexible ureteroscopy and methylene blue injection was used to identify the small ostium of infundibulum. Then infundibulectomy followed by lithotripsy was performed. All the patients receive double-J stents placement and traditional Chinese medicine for 1 to 3 months after operations. The stone clearance was estimated by kidney ureter bladder (KUB) within 3 months' follow up. RESULTS: The locations of calyceal diverticulum were upper pole in 7 patients, and interpolar regions in 4 patients. The average operation time was (123.7±59.6) min, and the average estimated blood loss was (29.3±32.1) mL. Successful flexible ureteroscopic holmium laser infundibulectomies were performed in all the 10 patients. Success rate was 100%. The stone clearance rates for 1 and 3 months after surgery were 50.0% and 80.0%, respectively, which were observed by KUB follow-up. Two patients had serious post-operative fever (>38.0 °C) in coexistence with chills. The mobidity of urosepsis was 20.0%. No major complications were identified. CONCLUSION: In selected patients, calyceal diverticular calculi with stenotic infundibulum can be treated safely and efficiently with flexible ureteroscopic homium laser lithotripsy. CTU and IVU should be completed preoperatively for calyceal diverticulum location and technique difficulty prediction. Retrograde methylene blue injection can be used to identify the ostium during surgery. And prolonged post-operation stone clearance was observed.

[Expression and clinical significance of glycoprotein non-metastatic melanoma protein B in human renal cell carcinoma].

OBJECTIVE: To investigate the role of glycoprotein non-metastatic melanoma protein B (GPNMB) in renal cell carcinoma (RCC). METHODS: The method of immunohistochemistry (IHC) and Western blot were utilized to examine the expression of GPNMB in RCC and the normal adjacent tissues matched. RESULTS: The expression of GPNMB was lower in RCC than in the matched normal adjacent tissues (P=0.022). CONCLUSION: The abnormal expression of GPNMB may play an important role in the development of RCC and the detection of GPNMB may be useful for the early diagnosis of tumor and its development.

[Free fatty acids induce proliferation of human renal carcinoma 786-O cell line via integrin-linked kinase].

OBJECTIVE: To investigate the effects of free fatty acids on cell proliferation and integrin-linked kinase (ILK) expression in human renal carcinoma 786-O cell line. METHODS: The 786-O cells were exposed to normal medium and different concentrations of oleic acid (OA) carried by de-fatty bovine serum albumin (d-BSA). The MTT assay and the flow cytometry assay were performed respectively for cell proliferation and apoptosis after the treatment with OA for 48 h. The expressions of ILK, Akt and p-Akt were detected by Western blot. RESULTS: The MTT assay showed that the cell viabilities of 0.05 mmol/L, 0.1 mmol/L and 0.2 mmol/L OA groups were increased gradually, as compared with the blank control (absorbance: 0.657 ± 0.056, 0.682 ± 0.028, 0.718 ± 0.042 vs. 0.495 ± 0.034; all P<0.001). The effects of OA on cells apoptosis were not significant (apoptotic rates: 2.42% ± 0.25% vs. 2.33% ± 0.87% vs. 2.25%± 0.51%, P=0.082). After being treated with OA, the expressions of ILK and p-Akt were increased in 786-O cells. CONCLUSION: The results suggested that free fatty acids could promote the development of renal cell carcinoma via up-regulating ILK/Akt pathway, which may reveal the relations between metabolic disturbance and renal carcinoma to a certain extent.

V.I.P. Score: A Comprehensive Grading System to Predict Difficulty of HoLEP Procedure for Small-to-Moderate Sized Prostate (<120 mL).

OBJECTIVE: To develop a comprehensive scoring system in addition to the conventionally used prostatic volume (PV), for predicting the difficulty of holmium laser enucleation of the prostate (HoLEP) that may arise with small-to-moderate sized prostate. METHODS: We retrospectively reviewed 151 consecutive patients who underwent HoLEP and had a PV less than 120 mL. Based on previous literature, a difficult procedure was defined as a prolonged operative time (OT>90 minute) in 88 cases, while the control group (OT≤90 minute) consisted of 63 patients. The clinical data, including age, body mass index, PV, intravesical prostatic protrusion (IPP), prostate specific antigen (PSA), prostate specific antigen density, urinary tract infection, microscopic hematuria, prior biopsy, diabetes mellitus, hypertension, history of acute urinary retention, catheter dependency and use of antiplatelet / anticoagulation drugs or 5-alpha reductase inhibitor were compared between the 2 groups. RESULTS: Univariate analysis revealed significant differences between the 2 groups. Multivariate analysis identified 3 main independent predictors for difficulty, including volume (V) (60-90 mL OR = 9.812, P < .001) (≥90 mL OR = 18.173, P = .01), IPP (I) (OR = 3.157, P = .018), and PSA (P) (≥4 ng/ml OR = 16.738, P < .001). Therefore, a V.I.P. score was developed based on the regression model and ranged from 0 to 7 points. The area under the curve showed preferable predictive ability of the V.I.P. score compared to PV (0.906 vs 0.869). CONCLUSION: We developed a V.I.P. score that can accurately predict the difficulty of the HoLEP procedure for PV less than 120 mL in order to optimize clinical outcomes.

[Inhibitory effect of CMTM5 on xenografted human prostatic cancer in nude mice].

OBJECTIVE: To investigate the inhibitory effect of CKLF-like MARVEL transmembrane domain containing 5 (CMTM5) on xenografted human prostatic cancer in nude mice and its action mechanism. METHODS: We established a model of xenografted prostatic cancer by inoculating PC-3 cells subcutaneously into nude mice, and 3 weeks later injected CMTM5 adenovirus locally into the tumor followed by daily observation of the tumor volume and body weight of the experimental animals. All the rats were killed 2 weeks after CMTM5 injection and the tumor tissue harvested for detection of the inhibitory effect of CMTM5 on the expressions of VEGF and NF-kappaB proteins by immunohistochemistry. RESULTS: The tumor volume was significantly smaller and body weight of the CMTM5-treated mice were (573.39 +/- 175.24) mm3 and (0.55 +/- 0.11) g, respectively, significantly decreased as compared with those of the controls ([1482.50 +/- 327.86] mm3 and [1.31 +/- 0.29] g) (P = 0.03 and P = 0.027). Immunohistochemistry showed that the expressions of VEGF and NF-kappaB were obviously down-regulated in the CMTM5 group in comparison with the control group. CONCLUSION: CMTM5 suppresses the growth of prostate cancer by down-regulating the expressions of VEGF and NF-kappaB.

Case report and literature review: Primary leiomyosarcoma of the penis.

Background: Leiomyosarcoma (LMS) is a malignant spindle-cell mesenchymal tumor originating from the smooth muscle cells, which mostly affects soft tissues and abdominopelvic organs over extremities. Primary LMS of the penis is a relatively uncommon mesenchymal tissue disease and a poorly understood condition. Case Report: A 69-year-old man presented with a growing, painless mass protruding from the penis. The irregularly lobulated lump was roughly 3 cm × 2.5 cm, with a smooth surface, tough texture, distinct boundary, and no tenderness. It was determined to be a penile tumor during the preoperative radiological evaluation. The patient underwent resection of the penile mass, followed by extended resection in the second operation. The diagnosis of LMS was verified by pathological examination. During a 20-month follow-up, the patient made a smooth recovery and remained disease-free. Conclusion: An immunohistochemical examination is essential for rendering this rare diagnosis. Radical excision of tumor lesions with negative cut margins is guaranteed to be the best treatment for primary penile LMS. Close follow-up should be provided due to the high rate of local recurrence.

The Significant Role of Tumor Volume on the Surgical Approach Choice, Surgical Complexity, and Postoperative Complications in Renal Cell Carcinoma With Venous Tumor Thrombus From a Large Chinese Center Experience.

Objective: To explore the role of tumor volume (TV) on surgical approach choice, surgical complexity, and postoperative complications in patients with renal cell carcinoma (RCC) and inferior vena cava tumor thrombus. Method: From January 2014 to January 2020, we retrospectively analyzed the clinical data of 132 patients who underwent radical nephrectomy with inferior vena cava thrombectomy (RN-IVCT). Primary renal tumor volume (PRTV), renal vein tumor thrombus volume (RVTTV), inferior vena cava tumor thrombus volume (IVCTTV), and total tumor thrombus volume (TTTV) were measured with the help of an internationally recognized 3D volume measurement software. The patients were divided into three groups according to the tumor volume within the inferior vena cava (IVC). Group 1 included 48 patients with IVCTTV between 0 and 15 cm3 (36.6%), group 2 included 38 patients with IVCTTV between 16 and 30 cm3 (28%), and group 3 included 46 patients with IVCTTV above 30 cm3 (35%). The three IVCTTV groups, as well as four different volume groups, were compared in terms of surgical approach choice, surgical complexity, and postoperative complications. One-way ANOVA and a non-parametric test were used to compare the clinicopathological characteristics and distribution differences between the three groups. Result: This study found significant differences among the three groups in the proportion of open surgery (P < 0.001), operation time (P < 0.044), intraoperative bleeding (P < 0.001), and postoperative complications (P < 0.001). When the four different volumes were compared, we found that for higher volumes IVCTTV and TTTV, open surgery is used more often compared with laparoscopic surgery (P < 0.001). In addition, with the increase in renal vein tumor thrombus volume, inferior vena cava tumor thrombus volume, and total tumor thrombus volume, the operation time also increased. Finally, with the increase in tumor thrombus volume and total tumor thrombus volume, the amount of intraoperative bleeding increased. Conclusion: With the increase in tumor volume, the proportion of open surgery and the incidence of postoperative complications increased. In addition, larger tumor volume prolongs operation time, increases intraoperative blood loss, and makes the surgery more complicated.

[Expression of glycoprotein non-metastatic melanoma protein B in prostate cancer and its significance].

OBJECTIVE: To investigate the expression of glycoprotein non-metastatic melanoma protein B (GPNMB) in prostate cancer and its clinical significance. METHODS: The expression of GPNMB was analysed in 63 prostate cancer and 3 heterosexual hyperplasia prostate tissue and 8 benign prostatic hyperplasia samples by immunohistochemical staining, with integral optical density(IOD) value representing expression level of positive cells. RESULTS: The expression of GPNMB was lower in benign prostatic hyperplasia (BPH, IOD=70 017.49) than in Atypical hyperplasia (IOD=101 547.33, P=0.000 1) . The expression of GPNMB in tumor (IOD= 162 027.54) was higher than in non-tumor group (IOD=79 290.97), which included BPH and atypical hyperplasia (P=0.000 1). But GPNMB expression level was not positively elevated with degree of malignancy of prostate cancer. However, the expression of GPNMB in low pathological grading(IOD=177 944.30) was higher than that in high pathological grading(IOD=150 885.81, P=0.013). CONCLUSION: The abnormal expression of GPNMB may play an important role in the development of prostate cancer and its detection may be useful for the early diagnosis of prostate cancer.

[Effect of integrin-linked kinase on the growth of prostate cancer in nude mice].

OBJECTIVE: To investigate the effect of the integrin-linked kinase (ILK) small interfering RNA (siRNA) on prostate cancer in nude mice by orthotopic injection of human cell line DU145. METHODS: The cultured human cell line DU145 was knocked down for ILK using a siRNA .Cellular ILK expression was quantified by RT-PCR and Western blot analysis. Moreover, cell attachment, invasiveness and microfilament dynamics assays were performed. Furthermore, the impact of the ILK siRNA on the prostate cancer was tested using a nude mice model in which prostate cancer was induced by orthotopic injection of human prostate cancer cell line DU145.Gross tumor volume of prostate in nude mice,cell differentiation,the state of apoptosis and proliferation were tested after 5 weeks of injection. RESULTS: The expression of ILK was suppressed significantly by siRNA, cellular mRNA and protein of ILK decreased 87% and 81% separately. The knockdown of ILK also induced the attachment and invasiveness of DU145 cell growing down. The tumor volume, cell differentiation, apoptosis index and proliferation index of prostate in nude mice of ILK siRNA orthotopic injection model were significantly smaller, better, increased and decreased separately than those in control group. CONCLUSION: Targeting inhibition of ILK not only decreases attachment and invasiveness of human DU145 cells, but also suppresses the growth and development of prostate cancer of orthotopic injection human DU145 cell line model in nude mice.

High expression of SMYD3 indicates poor survival outcome and promotes tumour progression through an IGF-1R/AKT/E2F-1 positive feedback loop in bladder cancer.

The AKT/mTOR pathway is critical for bladder cancer (BC) pathogenesis and is hyper-activated during BC progression. In the present study, we identified a novel positive feedback loop involving oncogenic factors histone methyltransferase SMYD3, insulin-like growth factor-1 receptor (IGF-1R), AKT, and E2F-1. SMYD3 expression was significantly up-regulated in BC tumors and positively associated with histological grade, lymph node metastasis, and shorter patient survival. Depletion of SMYD3 inhibited BC cell proliferation, colony formation, migration, invasion, and xenograft tumor growth. Mechanistically, SMYD3 inhibition led to the diminished AKT/mTOR signaling activity, thereby triggering deleterious effects on BC cells. Furthermore, SMYD3 directly activates the expression of IGF-1R, a critical activator of AKT in BC, by inducing hyper-methylation of histone H3-K4 and subsequent chromatin remodeling in the IGF-1R promoter region. On the other hand, E2F-1, a downstream factor of the AKT pathway, binds to the E2F-1 binding motifs at the SMYD3 promoter and consequently induces SMYD3 transcription and expression. Thus, SMYD3/IGF-1R/AKT/E2F-1 forms a positive feedback loop leading to the hyper-activated AKT signaling. Our findings provide not only profound insights into SMYD3-mediated oncogenic activity but also present a unique avenue for treating BC by directly disrupting this signaling circuit.

VHL-HIF-2α axis-induced SMYD3 upregulation drives renal cell carcinoma progression via direct trans-activation of EGFR.

It has been well established that the von Hippel-Lindau/hypoxia-inducible factor α (VHL-HIFα) axis and epidermal growth factor receptor (EGFR) signaling pathway play a critical role in the pathogenesis and progression of renal cell carcinoma (RCC). However, few studies have addressed the relationship between the two oncogenic drivers in RCC. SET and MYND domain-containing protein 3 (SMYD3) is a histone methyltransferase involved in gene transcription and oncogenesis, but its expression and function in RCC remain unclear. In the present study, we found that SMYD3 expression was significantly elevated in RCC tumors and correlated with advanced tumor stage, histological and nuclear grade, and shorter survival. Depletion of SMYD3 inhibited RCC cell proliferation, colony numbers, and xenograft tumor formation, while promoted apoptosis. Mechanistically, SMYD3 cooperates with SP1 to transcriptionally promote EGFR expression, amplifying its downstream signaling activity. TCGA data analyses revealed a significantly increased SMYD3 expression in primary RCC tumors carrying the loss-of-function VHL mutations. We further showed that HIF-2α can directly bind to the SMYD3 promoter and subsequently induced SMYD3 transcription and expression. Taken together, we identify the VHL/HIF-2α/SMYD3 signaling cascade-mediated EGFR hyperactivity through which SMYD3 promotes RCC progression. Our study suggests that SMYD3 is a potential therapeutic target and prognostic factor in RCC.

Association of dyslipidemia with renal cell carcinoma: a 1∶2 matched case-control study.

Abnormal serum lipid profiles are associated with the risk of some cancers, but the direction and magnitude of the association with renal cell carcinoma is unclear. We explore the relationship between serum lipids and renal cell carcinoma via a matched case-control study. A 1∶2-matched case-control study design was applied, where one renal cell carcinoma patient was matched to two non-renal-cell-carcinoma residents with respect to age (±0 year) and gender. Cases (n = 248) were inpatients with a primary diagnosis of renal cell carcinoma, confirmed by pathology after operations. Controls were sampled from a community survey database matched on age and gender with cases, 2 controls for each case. Stratified Cox proportional hazard regression analysis was used to obtain hazard ratios and corresponding 95% confidence intervals of lipids level and dyslipidemia for the risk of renal cell carcinoma. Elevated serum cholesterol (p<0.001), LDL cholesterol (p<0.001), and HDL cholesterol (p = 0.003) are associated with decreased hazard of renal cell carcinoma, adjusting for obesity, smoke, hypertension and diabetes. However, risk caused by hTG showed no statistical significance (p = 0.263). This study indicates that abnormal lipid profile influences the risk of renal cell carcinoma.

Effects of oleic acid on cell proliferation through an integrin-linked kinase signaling pathway in 786-O renal cell carcinoma cells.

An increased risk of renal cell carcinoma (RCC) has been linked with obesity and metabolic syndrome. However, the mechanisms by which lipid metabolic disorders affect the development of RCC remain unclear and highly controversial. Integrin-linked kinase (ILK) is a serine/threonine protein kinase involved in the regulation of tumor cell growth and angiogenesis. In the present study, the effect of free fatty acids in the promotion of RCC progression was investigated by upregulating ILK. Results of the MTT assay indicated that treatment of 786-O cells with oleic acid induced a concentration-dependent increase in cell viability. Flow cytometry analysis revealed that the effect of oleic acid on cell apoptosis was not significant. Following treatment with oleic acid, the expression of ILK, phospho-Akt and G protein-coupled receptor 40 (GPR40) was increased in 786-O cells. These effects were reversed when the expression of ILK was downregulated using specific small interfering RNA. These results indicate that free fatty acids are associated with the development of renal cell carcinoma via activation of the GPR40/ILK/Akt pathway, revealing a novel mechanism for the correlation between metabolic disturbance and renal carcinoma.

The potential role of a self-management intervention for benign prostate hyperplasia.

OBJECTIVE: To tentatively evaluate the usefulness of self-management interventions in improving the lower urinary tract symptoms (LUTS) and quality of life (QoL) in patients with benign prostatic hyperplasia (BPH). METHODS: Two-hundred twent-two men were recruited from a teaching hospital at Peking University from March 2008 to September 2009. They were referred by general practitioners to urologic outpatient departments because of BPH after 3-month administration of α-blockers. Participants were randomized to attend either a self-management program or undergo standard care. Difference of scores of International Prostate Symptom Score (IPSS) and BPH-specific QoL scale between 2 groups was analyzed at the enrollment period, and at the first week, third month, and sixth month. RESULTS: All participants had been followed for 6 months. There was no significant difference in IPSS score and QoL score between the 2 groups at the enrollment period and first week, whereas at the third month and sixth month, the IPSS scores and QoL self-management interventional group scores were statistically significant lower than those of the standard care group. CONCLUSION: Self-management intervention may be associated with decreased LUTS symptoms and may improve QoL in BPH patients with α-blocker administration.