Proxalutamide in metastatic castration-resistant prostate cancer: Primary analysis of a multicenter, randomized, open-label, phase 2 trial.

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).

ZBTB7A, a miR-144-3p targeted gene, accelerates bladder cancer progression via downregulating HIC1 expression.

BACKGROUND: Zinc finger and BTB domain-containing 7A (ZBTB7A) is a member of the POK family of transcription factors that plays an oncogenic or tumor-suppressive role in different cancers depending on the type and genetic context of cancer. However, the function and molecular mechanism of ZBTB7A in bladder cancer (BC) remain elusive. METHODS: The role of ZBTB7A in bladder cancer was detected by colony formation, transwell, and tumor formation assays. The expression levels of ZBTB7A, HIC1, and miR-144-3p were analyzed by qRT-PCR and Western blot. Bioinformatics analysis and a dual-luciferase reporter assay were used to assess the effect of ZBTB7A on the promoter activity of HIC1. RESULTS: The present study revealed that knockdown of ZBTB7A suppressed BC cell growth and migration, as indicated by an approximately 50% reduction in the number of colonies and an approximately 70% reduction in the number of migrated cells. Loss of ZBTB7A inhibited tumor growth in vivo, resulting in a 75% decrease in tumor volume and an 80% decrease in tumor weight. Further mechanistic studies revealed that ZBTB7A bound to the hypermethylated in cancer 1 (HIC1) promoter and downregulated HIC1 expression, accelerating the malignant behavior of BC. Increased expression of ZBTB7A in BC tissues was negatively corrected with the expression of HIC1. Moreover, ZBTB7A was a target of miR-144-3p, which decreased ZBTB7A expression in BC. CONCLUSION: Our data demonstrate that ZBTB7A, a targeted gene of miR-144-3p, promoted tumorigenesis of BC through downregulating HIC1 expression.

Clinical analysis of adrenal lesions larger than 5 cm in diameter (an analysis of 251 cases).

BACKGROUND: To describe the pathological distribution, imaging manifestations, and surgical managements and prognosis of large adrenal tumors (LATs) ≥ 5 cm METHODS: A total of 251 patients with LATs were analyzed on the basis of pathological or clinical diagnosis. Regarding surgery, open adrenalectomy was performed on 89 patients, and laparoscopic adrenalectomy was performed on 89 patients. Thirty-two patients with bilateral tumors were analyzed in terms of clinical characteristics. The survival rate was determined for 43 patients with adrenal metastases and 29 patients with primary adrenal malignancies. The CT characteristics including tumor diameter, shape, edge, heterogeneity, necrosis, calcification, pre-contrast attenuation, and contrast attenuation were analyzed for 117 patients. RESULTS: The majority of LATs were still benign, but they had a higher probability to be malignant. Benign LATs made up 68.13% of all cases, mainly adrenal cysts (19.52%), pheochromocytoma (18.73%), benign adenoma (16.73%), and myelolipoma (7.17%). Malignant LATs accounted for 28.69% of cases, mainly including adrenocortical carcinoma (8.76%) and metastases (17.13%). Laparoscopic surgery was found to involve less trauma than open surgery. It was also safer and postoperative recovery was faster, but it had drawbacks and could not completely replace open surgery. CT features had obvious specificity for the diagnosis of benign and malignant tumors. For example, benign adenomas had a smaller pre-contrast (< 10 Hu) whereas malignant adrenal tumors had, on the contrary, higher attenuation. Regarding adrenal malignant carcinoma, adrenal primary malignant tumors showed a better prognosis than adrenal metastases (mean survival of 19.17 months vs 9.49 months). Primary adrenal cortical carcinoma without metastasis had a better prognosis than primary adrenal cortical carcinoma metastasis (mean survival of 23.71 months vs 12.75 months), and adrenal solitary metastasis had a better prognosis than general multiple metastatic carcinoma (mean survival of 14.95 months vs 5.17 months). CONCLUSION: LATs were more likely to be benign; however, they still had a high probability of being a malignant tumor. Understanding the clinicopathological characteristics of LATs can facilitate selection of more effective clinical treatment options.

The safety and efficiency of retroperitoneal laparoscopic adrenalectomy via extra and intra perinephric fat approaches: a retrospective clinical study.

BACKGROUND: This retrospective clinical study is to evaluate the safety and efficiency of two different approaches in retroperitoneal laparoscopic adrenalectomy and provide experience and basis for the treatment of adrenal tumors through retroperitoneal approach. METHODS: From July 2015 to February 2018, 112 patients with adrenal lesions underwent retroperitoneal laparoscopic adrenalectomy (RLA) using a 3-port method. Among them, 56 patients underwent RLA via the extra perinephric fat approach (EPFA), 56 patients underwent RLA via the intra perinephric fat approach (IPFA). Clinical data, including preoperative, operative and postoperative management were recorded. RESULTS: All surgeries were successfully completed, and there was no single patient who died during these surgeries. There was no statistically significant difference between the two groups in blood loss, postoperative complications, vena cava injury, renal cortex injury, peripheral organ injury, and post operation hospital stay. Peritoneum injury occurred more frequently in the EPFA group when compared with the IPEA group (p = 0.042). The average surgery time of the IPEA group is significantly shorter when compared with that of the EPEA group (p < 0.001). Due to serious saponification of the perinephric fat and heavy adhesion to renal fascia, three cases in IPFA group were converted to the EPFA surgery. CONCLUSION: RLA is a safe and effective procedure both via extra perinephric fat and intra perinephric fat approaches. IPEA is superior to EPEA in terms of peritoneal injury and duration. The choice may mainly depend on the experience of the surgeon, the characteristics of the adrenal tumor and the nature of the perinephric fat.

Long noncoding RNA lung cancer associated transcript 1 promotes proliferation and invasion of clear cell renal cell carcinoma cells by negatively regulating miR-495-3p.

Recently, long noncoding RNAs have emerged as new gene regulators and prognostic markers in several cancers, including renal cell carcinoma (RCC). Here, we focused on the long noncoding RNA lung cancer associated transcript 1 (LUCAT1) based on clear cell RCC (ccRCC) the cancer genome atlas (TCGA) data. However, whether aberrant expression of LUCAT1 in ccRCC is correlated with malignancy, metastasis or prognosis has not been elucidated. In the current study, we found that the expression of LUCAT1 was upregulated in ccRCC tissues and cancer cell lines. Upregulated LUCAT1 was positively correlated with larger tumor size, advanced tumor-node-metastasis (TNM) stage, higher smoking frequency, nodal metastasis and shorter overall survival in patients with ccRCC. Inhibition of LUCAT1 by small interfering RNA reduced cell proliferation and invasion of ccRCC cells in vitro. In vivo assay showed that the tumor volume and weight were lower in the group of LUCAT1 inhibition than that in the control group. We then found that LUCAT1 directly bound and inhibited the expression of micoRNA-495-3p (miR-495-3p), which subsequently regulated the expression of special adenine-thymine (AT)-rich DNA-binding protein 1 (SATB1). Collectively, LUCAT1 was critical for proliferation and invasion of ccRCC cells by regulating miR-495-3p and SATB1. Our findings indicated that LUCAT1 and miR-495-3p may offer potential novel therapeutic targets of treatment of ccRCC.

KLF4, a miR-32-5p targeted gene, promotes cisplatin-induced apoptosis by upregulating BIK expression in prostate cancer.

BACKGROUND: Chemotherapeutic insensitivity remains a big challenge in prostate cancer treatment. Recently, increasing evidence has indicated that KLF4 plays a key role in prostate cancer. However, the potential biological role of KLF4 in Chemotherapeutic insensitivity of prostate cancer is still unknown. METHODS: The role of KLF4 in cisplatin-induced apoptosis was detected by western blotting and a cell counting kit (CCK8). The potential molecular mechanism of KLF4 in regulating prostate cancer chemosensitivity was investigated by RNA sequencing analysis, q-RT-PCR, western blotting and chromatin immunoprecipitation (ChIP). The expression level of KLF4 mediated by miR-32-5p was confirmed by bioinformatic analysis and luciferase assays. RESULTS: Here, we found that KLF4 was induced by cisplatin in prostate cancer cells and that the increase in KLF4 promoted cell apoptosis. Further mechanistic studies revealed that KLF4 directly bound to the promoter of BIK, facilitating its transcription. Additionally, we also found that the gene encoding KLF4 was a direct target of miR-32-5p. The downregulation of miR-32-5p in response to cisplatin treatment promoted KLF4 expression, which resulted in a increase in the chemosensitivity of prostate cancer. CONCLUSION: Thus, our data revealed that KLF4 is an essential regulator in cisplatin-induced apoptosis, and the miR-32-5p-KLF4-BIK signalling axis plays an important role in prostate cancer chemosensitivity.

Impact of tumor architecture on disease recurrence and cancer-specific mortality of upper tract urothelial carcinoma treated with radical nephroureterectomy.

Upper tract urinary carcinoma (UTUC) is a relatively uncommon but aggressive disease. Recent publications have assessed the prognostic significance of tumor architecture in UTUC, but there is still controversy regarding the significance and importance of tumor architecture on disease recurrence. We retrospectively reviewed the medical records of 101 patients with clinical UTUC who had undergone surgery. Univariate and multivariate analyses were conducted to identify factors associated with disease recurrence and cancer-specific mortality. As our single center study and the limited sample size may influence the clinical significance, we further quantitatively combined the results with those of existing published literature through a meta-analysis compiled from searching several databases. At a median follow-up of 41.3 months, 25 patients experienced disease recurrence. Spearman's correlation analysis showed that tumor architecture was found to be positively correlated with the tumor location and the histological grade. Kaplan-Meier curves showed that patients with sessile tumor architecture had significantly poor recurrence free survival (RFS) and cancer specific survival (CSS). Furthermore, multivariate analysis suggested that tumor architecture was independent prognostic factors for RFS (Hazard ratio, HR = 2.648) and CSS (HR = 2.072) in UTUC patients. A meta-analysis of investigating tumor architecture and its effects on UTUC prognosis was conducted. After searching PubMed, Medline, Embase, Cochrane Library and Scopus databases, 17 articles met the eligibility criteria for this analysis. The eligible studies included a total of 14,368 patients and combined results showed that sessile tumor architecture was associated with both disease recurrence with a pooled HR estimate of 1.454 and cancer-specific mortality with a pooled HR estimate of 1.416. Tumor architecture is an independent predictor for disease recurrence after radical nephroureterectomy for UTUC. Therefore, closer surveillance is necessary, especially in patients with sessile tumor architecture.

[Safety and efficacy of China-made sildenafil citrate in the treatment of erectile dysfunction].

OBJECTIVE: To evaluate the safety, efficacy and tolerability of China-made sildenafil citrate (Jinge) in the treatment of ED. METHODS: We conducted a multi-center, randomized, double-blind and placebo-controlled clinical trial among 222 ED patients in five urological or andrological clinics of China. The patients were randomly assigned to receive sildenafil citrate (SC, n = 111) or placebo (n = 111) for 8 weeks. We obtained and analyzed the demographic and clinical characteristics of the patients, the scores of International Index of Erectile Function (IIEF), the success rate of sexual intercourse, and the incidence of adverse events. RESULTS: No statistically significant differences were found between the patients of the SC and those of the placebo group in the mean age (ï¼»47.2±11.32ï¼½ yr vs ï¼»46.67±13.08ï¼½ yr, P>0.05), psychological etiology (27.93% vs 23.42%, P>0.05), organic etiology (21.62% vs 29.73%, P>0.05) or mixed etiology (50.45% vs 46.85%, P>0.05), nor in height, weight, nationality, or history of smoking, drinking or allergy. Compared with the placebo controls, the SC-treated patients showed significant increases in the excellence rate of effectiveness (29.91% vs 78.90%, P<0.01), success rate of sexual intercourse (29.16% vs 63.87%, P<0.01), and total effectiveness rate (34.58% vs 77.98%, P<0.01). The effectiveness rates on organic, psychogenic and mixed types ED were remarkably higher in the SC group (64.52%, 83.33%, and 82.14%) than in the placebo control (46.15%, 21.21%, and 25.00%) (P<0.01). Mild or temporary adverse events were observed in 32 cases in the SC group as compared with 13 in the placebo control. CONCLUSIONS: China-made sildenafil citrate is an effective, safe and well-tolerated drug for ED of different etiologies in the Chinese population.

Is Overexpression of Ki-67 a Prognostic Biomarker of Upper Tract Urinary Carcinoma? A Retrospective Cohort Study and Meta-Analysis.

BACKGROUND: Upper tract urinary carcinoma (UTUC) is a relatively uncommon but aggressive disease. The Ki-67 antigen is a classic marker of cellular proliferation, but there is still controversy regarding the significance and importance of Ki-67 in tumor progression. METHODS: In this study, we first detected Ki-67 expression in UTUC patients by immunohistochemistry (IHC). Subsequently, we quantitatively combined the results with those from the published literature in a meta-analysis after searching several databases. RESULTS: IHC results demonstrated that patients with muscle-invasive tumors (T2-T4) had higher Ki-67 expression than those with non-muscle-invasive tumors (Tis-T1), suggesting that high Ki-67 expression may be associated with the aggressive form of UTUC. Kaplan-Meier curves showed that patients with high Ki-67 expression had significantly poorer cancer-specific survival (CSS) and disease-free survival (DFS). Furthermore, multivariate analysis suggested that Ki-67 expression was an independent prognostic factor for CSS (hazard ratio, HR=3.196) and DFS (HR=3.517) in UTUC patients. Then, a meta-analysis of the published literature investigating Ki-67 expression and its effects on UTUC prognosis was conducted. After searching the PubMed, Medline, Embase, Cochrane Library and Scopus databases, 12 articles met the eligibility criteria for this analysis. The eligible studies included a total of 1740 patients with a mean number of 82 patients per study (range, 38-475). The combined results showed that increased Ki-67 levels were associated with poor survival and disease progression, with a pooled HR estimate of 2.081 and 2.791, respectively. In subgroup analysis, the pooled HR was statistically significant for cancer-specific survival (HR=2.276), metastasis-free survival (HR=3.008) and disease-free survival (HR=6.336). CONCLUSIONS: In conclusion, high Ki-67 expression was associated with poor survival in patients with UTUC, as well as a high risk of disease progression, although these findings need to be interpreted with caution. Large-scale, adequately designed, prospective trials are needed to further confirm the value of Ki-67 in prognosis of UTUC patients.

Effect of AQP9 Expression in Androgen-Independent Prostate Cancer Cell PC3.

It is known that aquaporin 9 (AQP9) in the prostate was strictly upregulated by androgen and may represent a novel therapeutic target for several cancers, but whether AQP9 plays a role in the regulation of androgen-independent prostate cancer still remains unclear. In the present study, AQP9 was determined in prostate cancer and adjacent cancer tissues; AQP9-siRNA was applied to silencing AQP9 in androgen-independent prostate cancer cell PC3 cell line. Western blot and flow cytometry analysis were employed to detect changes in related-function of control and AQP9-siRNA groups. The results showed that AQP9 is significantly induced in cancer tissues than that in adjacent cancer tissues. Moreover, knockdown of AQP9 in PC3 androgen-independent prostate cancer cell prostate cancer cells increased inhibition rates of proliferation. In addition, knockdown of AQP9 resulted in a significant decrease in the expression of the Bcl-2 and with a notable increase in the expression of Bax and cleaved caspase 3, indicated that AQP9 knockdown promoted apoptosis in prostate cancer cells. From wound healing assay and matrigel invasion, we suggested that AQP9 expression affects the motility and invasiveness of prostate cancer cells. Moreover, In order to explore the pathway may be involved in AQP9-mediated motility and invasion of prostate cancer cells, the phosphorylation of ERK1/2 was significant suppressed in AQP9 siRNA-transfected cells compared with that in control cells, suggesting that AQP9 is involved in the activation of the ERK pathway in androgen-independent prostate cancer cells.

MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor PDCD4 and promotes cell transformation, proliferation, and metastasis in renal cell carcinoma.

OBJECTIVES: MiR-21 induces neoplastic transformation, cell proliferation, and metastasis and downregulates programmed cell death4 (PDCD4) in some cancers. The aim of this study was to investigate the roles and interactions of PDCD4 and miR-21 in human renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 32 paired tumor and normal tissue specimens from RCC patients as well as three renal cancer cell lines (786-O, A498, caki-1) and one normal epithelial kidney cell line (HK-2) were studied. The expression levels of PDCD4 (protein and mRNA) and miR-21 were examined by Western blot analysis and by qRT-PCR and luciferase reporter assays. Furthermore, we transfected 786-O cells with pre-miR-21 (mimics) and anti-miR-21 (inhibitor) and then again analyzed the expression of PDCD4 protein and mRNA, and determined cell proliferation and transformation capabilities by EDU and soft agar colony formation assay. RESULTS: MiR-21 expression was significantly upregulated in RCC, metastatic RCC specimens and renal cancer cell lines (A498, 786-O, caki-1) compared to normal non-metastatic RCC specimens and HK-2 cells (P<0.05). In contrast, PDCD4 protein expression significantly decreased (P<0.05), whereas PDCD4 mRNA expression remained unaltered (P>0.05). Moreover, we observed a significant reduction in PDCD4 protein levels in miR-21mimic-transfected cells, but a significant increase in miR-21inhibitor-transfected cells (P<0.05), whereas PDCD4 mRNA was practically unaltered (P>0.05). Furthermore, miR-21mimic-transfected cells exhibited increased cell proliferation and transformation capacity according to EDU analysis and soft agar formation assay, whereas miR-21inhibitor-transfected cells exhibited the opposite phenomenon(P<0.05). CONCLUSIONS: MiR-21 not only promoted cancer cell hyperplasia and contributed to tumor cell transformation and metastasis, but also post-transcriptionally downregulated PDCD4 protein expression. PDCD4 and miR-21 expression levels potentially play an important role in renal cell cancer.

Visceral fat accumulation is associated with different pathological subtypes of renal cell carcinoma (RCC): a multicentre study in China.

OBJECTIVE: To investigate whether visceral obesity is associated with certain histological subtypes of renal cell carcinoma (RCC) ina multicentre Chinese cohort. PATIENTS AND METHODS: A kidney tumour database was created using three tertiary centres in China; 487 patients were enrolled presenting with localised RCC and complete computer tomography(CT)/magnetic resonance imaging (MRI) information. A single-slice CT image was used to measure the area of visceral and subcutaneous adipose tissues in each patient. Statistical methods were used to analyse clear-cell RCC (ccRCC) and non-clear-cell RCC (non-ccRCC) as they relate to visceral fat area (VFA) and other risk factors, such as age, gender, tumour size, diabetes, hypertension, total fat area (TFA) and body mass index (BMI). RESULTS: In all, 418 patients had a ccRCC subtype and 69 had a non-ccRCC subtype. For all the patients with RCC, the mean VFA was 102 cm2, while mean BMI was 24 kg/m2. The mean VFA was greater in ccRCC than non-ccRCC patients by 25 cm2. There were significant differences in the mean VFA and TFA between patients with ccRCC and those with non-ccRCC.Multivariate analysis showed that the presence ofVFA was more important than the effects of BMI and Type 2 diabetes on pathology prediction. In patients with a normal BMI, those with a higher quartile of VFA were more likely to develop ccRCC than those with a low VFA. CONCLUSIONS: Increased visceral fat was found to be associated with ccRCC and the significance of VFA outweighed the effects of BMI and Type 2 diabetes for the prediction of RCC pathology in multivariate analyses. As a result, VFA could constitute a primary explanation for the link between obesity and ccRCC.

[Retracted] Isoquercitrin inhibits bladder cancer progression in vitro and in vivo by regulating the PI3K/Akt and PKC signaling pathways.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the agarose gel electrophoretic bands shown in Fig. 4A for PKC were strikingly similar to bands that had already appeared in another article written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 36: 165­172, 2016; DOI: 10.3892/or.2016.4794].

Zinc sensitizes prostate cancer cells to sorafenib and regulates the expression of Livin.

In prostate carcinogenesis, normal zinc-accumulating epithelial cells are transformed into malignant cells that do not accumulate zinc. Increased levels of zinc have been shown to induce apoptosis through a caspase-dependent mechanism with down-regulated anti-apoptotic proteins in prostate cancer cells. Our previous study showed that, as a member of the inhibitor of apoptosis proteins (IAPs) family, Livin could play an important role in the initiation of human prostate cancer and promote cell proliferation by altering the G1-S cell cycle transition. In the present study, we measured the apoptosis sensitivity of prostate cancer cells to zinc and sorafenib and found that zinc sensitized prostate cancer cells to sorafenib-induced apoptosis. Surprisingly, we also found that, unlike its counterparts Survivin and cIAP2, Livin was not decreased all the time; instead, it was compensatively increased in zinc-mediated apoptosis at 48 h in prostate cancer cells. Our results offer potential treatment combinations that may augment the effect of sorafenib, and also reveal, for the first time, that increased Livin expression may play a role in the early cell death response of prostate cancer cells to zinc.

Can tamsulosin facilitate expulsion of ureteral stones? A meta-analysis of randomized controlled trials.

OBJECTIVES: To determine the efficacy and safety of the adrenergic alpha-antagonist tamsulosin in facilitating ureteral stones expulsion. METHODS: A literature search was carried out using the PubMed database, Medline via Ovid, Embase and the Cochrane Library database to identify randomized controlled trials evaluating the efficiency of tamsulosin in the treatment of ureteral stones. Meta-analysis and forest plots were carried out by use of Review Manager version 5.1 software (Cochrane Collaboration). RESULTS: Compared with the control group, the tamsulosin group had an increase in expulsion rate of 51% and a decrease in expulsion time of 2.63 days. Furthermore, tamsulosin was found to reduce the risk of ureteral colic during treatment by 40% and also the risk of requirement of auxiliary procedures during follow up by 60%. In terms of safety, the tamsulosin group had a 117% increase in the incidence of side-effects compared with the control group, especially for incidence of dizziness. CONCLUSION: Tamsulosin facilitates the expulsion of ureteral calculi by providing a higher expulsion rate, a shorter expulsion time, a lower incidence of ureteral colic during treatment and a lower requirement of auxiliary procedures. However, the incidence of dizziness occurring during tamsulosin treatment is significantly higher in this setting.

[Efficacies of sorafenib plus interferon in advanced renal cell carcinoma: a report of 57 cases].

OBJECTIVE: To explore the efficacies and adverse events of sorafenib in the treatment of advanced metastatic renal cell carcinoma. METHODS: A total of 57 patients with advanced kidney cancer were recruited from our hospital from April 2007 to October 2011. They were divided into sorafenib group (A, n = 24) and sorafenib + IFN group (B, n = 33). The primary endpoints included objective response rate and progression-free survival (PFS). And the secondary endpoints were overall survival (OS) and incidence of adverse events. RESULTS: The mean medication time of group A was 15 (7-56) months. The outcomes were partial response (PR, n = 1), stable disease (SD, n = 8), progressive disease (PD, n = 1) and death (n = 14). The rates of objective response and disease control were 4.2% (1/24) and 37.5% (9/24) respectively. For group B, the mean medication time was 15 (4-30) months. The outcomes were PR (n = 2), and include 2 patients of PR, 21 examples of SD, 1 patient of PD and death. The rates of objective response and disease control were 6.1% (2/33) and 69.7% (23/33) respectively. Two groups had no significant difference in incidence or severity of adverse events (both P > 0.05). CONCLUSIONS: As a safe and effective agent for advanced kidney cancer, sorafenib is well-tolerated in patients. The combined use of interferon may improve the therapeutic efficacies without an occurrence of adverse events.

[Effects of neoadjuvant chemotherapy on the prognostic mortality risk of invasive transitional bladder cancer: a meta-analysis].

OBJECTIVE: To systematically assess the effects of neoadjuvant chemotherapy on the prognostic risk of invasive transitional bladder cancer. METHODS: All known randomized controlled trials (RCTs) on neoadjuvant chemotherapy in the treatment of invasive transitional bladder cancer, published from the date of database building to September 2012, were retrieved from such databanks as Pubmed, CBMdisc, Embase and Cochrane. The data on 5-year survival rate of included studies were extracted for further heterogeneity exploration, subgroup analysis and statistical pooling with the RevMan 5.10 software. RESULTS: Fourteen subjects involving 2072 cases and 2086 controls were published from 1991 to 2012. The overall odds ratio of survival suggested a 21% relative reduction in mortality risk for neoadjuvant chemotherapy compared to that on control (OR = 0.79, 95%CI:0.70-0.90). In subgroup analysis according to different neoadjuvant chemotherapies, MCV (methotrexate, cisplatin and vinblastine) and MVAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapies showed significant benefit to overall survival with 28% and 25% reduction in risk of death respectively (OR = 0.72,95%CI:0.60-0.86, OR = 0.75,95%CI:0.59-0.96) . However, no significant difference existed in effects between C (cisplatin) chemotherapy, CM (cisplatin and methotrexate) chemotherapy and CD (cisplatin and docetaxel) chemotherapy and controls. In subgroup analysis according to local treatment of cystectomy or radiotherapy after neoadjuvant chemotherapy, the patients with cystectomy showed significant benefits in overall survival with 25% reduction in risk of death (OR = 0.75, 95%CI:0.65-0.87). However, the patients with radiotherapy or radiotherapy plus cystectomy showed no significant benefits in overall survival. CONCLUSIONS: MCV and MVAC neoadjuvant chemotherapies improve survival among patients with bladder cancer. And neoadjuvant chemotherapy has better long-term survival after cystectomy.

[Clinical research on the correlations between type 2 diabetes mellitus and renal clear cell carcinoma].

OBJECTIVE: To investigate the relationship between renal clear cell carcinoma and type 2 diabetes mellitus (DM). METHODS: Two hundreds and sixty-four patients with renal clear cell carcinoma and four hundred controls who suffered from non-urinary system, non-neoplastic or non-hormone-related disorders, were enrolled from January 2008 to December 2012. The incidence of diabetes between the 2 groups and the relationship between renal clear cell carcinoma and duration of diabetes were compared, moreover, renal clear cell carcinoma patients with DM were compared with patients without DM for their clinical features, laboratory examinations and histological characteristics. RESULTS: The comparison of renal clear cell carcinoma group and control group: the incidence of DM in the two groups were 19.7% and 12.8% respectively, and the difference was significant (χ(2) = 5.86, P < 0.05, OR = 1.68). In the renal clear cell carcinoma group, the proportion of patients with DM diagnosed within 2-4 years was 4.92%, which were significant higher than those in the control group 1.70% (χ(2) = 5.49, P < 0.05, OR = 2.91). And men with diabetes had high occurrence risk 86% of renal clear cell carcinoma (OR = 1.86, 95%CI: 1.09-3.15). The comparison of diabetes patients subgroup and non-diabetic patients subgroup in renal clear cell carcinoma group: in respect of clinical features, greatest tumor diameter in the two subgroups were (4.9 ± 2.3) cm and (4.2 ± 2.1) cm respectively, and the difference was significant (t = 1.96, P < 0.05). However, there was no significant difference in terms of age, gender and cancer location between the two subgroups (P > 0.05). In respect of laboratory examinations, serum creatinine in the two subgroups were (72 ± 20) µmol/L and (65 ± 17) µmol/L, and the difference was significant (t = 2.34, P < 0.05); serum urea nitrogen in the 2 subgroups were (7.1 ± 2.1) mmol/L and (6.0 ± 1.5) mmol/L respectively, and the difference was significant too (t = 1.47, P < 0.05). In respect of histological characteristics, the proportion of well differentiated clear cell carcinoma were 80.8% and 81.1% respectively, and the difference was significant (χ(2) = 4.23, P < 0.05). The proportion of stage II were 25.0% and 27.8% respectively and the difference was significant (χ(2) = 4.08, P < 0.05). CONCLUSIONS: DM is closely related with renal clear cell carcinoma and DM may be a possible risk factor for the tumor. And for elderly patients with diabetes who appear waist discomfort or hematuria, a careful examination of kidney is important to make early diagnosis, give timely treatment and improve survival prognosis.

Livin regulates prostate cancer cell invasion by impacting the NF-κB signaling pathway and the expression of FN and CXCR4.

Prostate cancer (PCa) has the second highest mortality rate of all tumor-related diseases for males in Western countries, and the incidence of PCa in China is increasing. Previous studies have proven that inhibitor of apoptosis proteins (IAPs) can regulate tumor cell invasion and metastasis. Livin is the most recently identified IAP. Our previous study showed that Livin might play an important role in the initiation of human PCa and that Livin-α might promote cell proliferation by regulating the G1-S cell cycle transition. However, whether Livin, as an IAP, can regulate the invasive ability of PCa cells remains unknown. In this study, we found that the expression of Livin was higher in metastatic PCa tissues than in nonmetastatic tissues and that the expression of Livin was downregulated/upregulated by small interfering RNA/vector, which could inhibit/promote PC-3/LNCaP cell invasion. This action was related to the impact of Livin on nuclear factor-κB (NF-κB) and its downstream signaling pathway, including FN and CXCR4. Together, our findings suggested that Livin might regulate tumor cell invasion in PCa directly, and that Livin might be an ideal candidate for preventing tumor cell invasion.