Melatonin potentiates the antitumor effect of curcumin by inhibiting IKKß/NF-κB/COX-2 signaling pathway.

Curcumin, a natural polyphenolic compound, has commonly been used as a food additive or in many traditional medicine remedies for over 2,000 years in many Asian countries. Melatonin is a hormone secreted from pineal glands of mammals and possesses diverse physiological functions. Both curcumin and melatonin have the effective potential to inhibit proliferation of various types of cancers, but there is no report on their combination for bladder cancer treatment, and the underlying mechanism remains poorly understood. In the present study, we investigated whether the combination of curcumin and melatonin leads to an enhanced inhibition of cell proliferation in bladder cancer cells. Our results showed that the combinational treatment enhanced the repression of nuclear translocation of NF-κB and their binding on COX-2 promoter via inhibiting IKKß activity, resulting in inhibition of COX-2 expression. In addition, combined treatment with curcumin and melatonin induced cell apoptosis in bladder cancer through enhancing the release of cytochrome c from the mitochondrial intermembrane space into the cytosol. These results, therefore, indicated that melatonin synergized the inhibitory effect of curcumin against the growth of bladder cancer by enhancing the anti-proliferation, anti-migration, and pro-apoptotic activities, and provide strong evidence that combined treatment with curcumin and melatonin might exhibit an effective therapeutic option in bladder cancer therapy.

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

Bladder cancer is the most common malignancy of the urinary system and is also one of the 10 most common cancers of the human body. Currently, clinical treatment of bladder cancer mainly utilizes partial or total cystectomy, supplemented by conventional chemotherapy. However, such treatment has not fully improved the prognosis of patients and is associated with various side effects. Studies have found that flavonoids extracted from plants can be used in radiotherapy and chemotherapy for the prevention of postoperative recurrence and metastasis but also alone for the treatment of advanced tumors. Both applications can ameliorate clinical symptoms, improve the quality of life, and prolong the survival of patients. Based on the above information, the present study investigated the effect of isoquercitrin, a type of flavonoid found in Bidens pilosa L. extracts, on bladder cancer progression, with the goal of understanding the biological characteristics of isoquercitrin by which it participates in bladder cancer progression. Using in vitro experiments, we found that therapeutic doses of isoquercitrin significantly inhibited cell proliferation and induced apoptosis in human bladder cancer cells and that the cell cycle was arrested in the G1 phase. Isoquercitrin inhibited phosphatidylinositol 3-kinase (PI3K) and Akt phosphorylation expression levels, thus inhibiting proliferation and inducing apoptosis in the cancer cells. In addition, we found that isoquercitrin reduced protein kinase C (PKC) protein expression levels in the human bladder cancer cell lines. We also showed via in vivo experiments that isoquercitrin inhibited xenograft tumor growth in nude mice. In conclusion, our study confirmed that isoquercitrin inhibits bladder cancer progression in vivo and demonstrated that the molecular mechanism of this inhibition may be closely associated with the PI3K/Akt and PKC signaling pathways.

Prognostic analysis of Chinese patients with metastasis renal cell cancer receiving sorafenib: results from a multicenter long-term follow-up retrospective study.

The effects of sorafenib for Chinese patients with metastatic renal cell cancer (mRCC) were evaluated to figure out the relationship between clinical variables and prognosis. The data were analyzed retrospectively from six comprehensive cancer centers in Northeast China. All cases were diagnosed as mRCC histopathologically without exception. Patients were taken 400 mg sorafenib orally twice daily until progression of disease or intolerable toxic reaction occurred. Overall survival (OS), progression-free survival (PFS), and the influence of clinical variables on survival were appointed as main outcome measures. Clinical data were analyzed using SPSS statistical software. P<0.05 was considered as statistically significant. A total of 131 patients were available for survival analysis. The median follow-up periods were 16.9 months, and the median OS and PFS were 16.1 months and 10.5 months, respectively. Univariate analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), metastatic sites, and previous therapy were significantly associated with OS, whereas PFS was merely associated with ECOG PS and previous therapy. The multivariate analysis suggested that ECOG PS, metastatic sites, and previous therapy were the independent prognostic factors for OS, and ECOG PS and previous therapy as the independent prognostic factors for PFS. In the subgroup analysis for patients with visceral metastasis, the prognosis of patients with lung metastasis alone was better than those cases with liver metastasis alone or multiple organs metastasis. In our study, sorafenib shows a higher curative activity for patients with mRCC in Northeast China. ECOG PS, metastatic lesions, and previous therapy may be important parameters for OS and PFS prediction. Lung metastases alone may be a more sensitive indicator for sorafenib than other organ metastases.

[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.

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.

[Transurethral prostatectomy with the bipolar plasmakinetic technique for benign prostate hyperplasia: a report of 712 cases].

OBJECTIVE: To evaluate the effect and safety of transurethral prostatectomy with the bipolar plasmakinetic technique (PKRP) in the treatment of benign prostate hyperplasia (BPH). METHODS: A total of 712 BPH patients underwent transurethral prostatectomy with the bipolar plasmakinetic technique. The patients averaged 70.6 years of age and 52 g (range 35-102 g) in estimated prostate weight preoperatively. Comparative analyses were made on the maximum urine flow rate (Qmax), residual urine volume and scores on IPSS and QOL obtained pre- and post-operatively. RESULTS: The operations lasted 20-120 minutes (mean 51 min), the resected tissues weighed 15-96 g (mean 46 g), and no transurethral resection syndrome (TURS) occurred. The catheters were removed 4 -5 days after surgery. The patients were followed up for 1 -52 months (mean 27.6 mo). Obvious reduction was observed in the average Qmax from 4.7 ml/s preoperatively to 19. 1 ml/s postoperatively, in the mean IPSS score from 26.6 to 5. 8, and in the mean QOL score from 5.4 to 1.7, all with significant differences (P < 0.01). CONCLUSION: Transurethral prostatectomy with the bipolar plasmakinetic technique is a safe and effective means for the treatment of BPH.

[Transurethral prostatectomy with the bipolar plasma kinetic technique for benign prostate hyperplasia: a report of 297 cases].

OBJECTIVE: To evaluate the effect and safety of transurethral prostatectomy with the bipolar plasma kinetic technique (PKRP) in the treatment of benign prostate hyperplasia(BPH). METHODS: Two hundred and ninty-seven BPH patients underwent transurethral prostatectomy with the bipolar plasma kinetic technique. The preoperative estimated weight of the prostate ranged from 35 g to 102 g, averaging 52 g. RESULTS: The operation lasted 40 approximately 65 min, averaging 51 min. The resected tissues weighed 40 approximately 80 g, averaging 46 g. During the operation no transurethral resection (TUR) syndrome occurred. The catheter was removed 4 approximately 5 days after the operation, all with fluent urination. The patients were followed up for 2 approximately 33 months. IPSS decreased from average 31.5 preoperatively to average 6.8 postoperatively (P < 0.001). Average maximum flow-rate (Q(max)) decreased from 6.3 ml/s preoperatively to 18.6 ml/ s postoperatively (P < 0.001). Preoperative average residual urine was 97 ml and reduced to average 9 ml after the operation. Temporary incontinence occurred in 4 cases, perioperative hemorrhage in 2, and urethral stricture in 1. CONCLUSION: Transurethral prostatectomy with the bipolar plasma kinetic technique is a safe and effective means for the treatment of BPH.