Correction: CuI-mediated synthesis of 1-aryl-5,6,7-trimethoxybenzimidazoles as potent antitubulin agents.

[This corrects the article DOI: 10.1039/D3RA01927F.].

CuI-mediated synthesis of 1-aryl-5,6,7-trimethoxybenzimidazoles as potent antitubulin agents.

In situ CuI-mediated cyclization methodology helped yield benzimidazoles with different substitution manner, such as 1,2-diarylbenzimidazoles (4 and 5) and 1-arylbenzimidazoles (6-15). The result of structure-activity relationship (SAR) study confirmed the significance of the 5,6,7-trimethoxybenzimidazole moiety, and the representative derivatives (8-10) exhibited marked antiproliferative activity against A549, HCT-116, and PC-3 cells; in addition, they are able to inhibit the polymerization of tubulin. Among them, compound 10 inhibited the growth of A549, HCT-116, and PC-3 cells with a mean IC50 value of 0.07 µM, and its IC50 value of tubulin polymerization is 0.26 µM.

ZnO Nanoparticles Induced Caspase-Dependent Apoptosis in Gingival Squamous Cell Carcinoma through Mitochondrial Dysfunction and p70S6K Signaling Pathway.

Zinc oxide nanoparticles (ZnO-NPs) are increasingly used in sunscreens, food additives, pigments, rubber manufacture, and electronic materials. Several studies have shown that ZnO-NPs inhibit cell growth and induce apoptosis by the production of oxidative stress in a variety of human cancer cells. However, the anti-cancer property and molecular mechanism of ZnO-NPs in human gingival squamous cell carcinoma (GSCC) are not fully understood. In this study, we found that ZnO-NPs induced growth inhibition of GSCC (Ca9-22 and OECM-1 cells), but no damage in human normal keratinocytes (HaCaT cells) and gingival fibroblasts (HGF-1 cells). ZnO-NPs caused apoptotic cell death of GSCC in a concentration-dependent manner by the quantitative assessment of oligonucleosomal DNA fragmentation. Flow cytometric analysis of cell cycle progression revealed that sub-G1 phase accumulation was dramatically induced by ZnO-NPs. In addition, ZnO-NPs increased the intracellular reactive oxygen species and specifically superoxide levels, and also decreased the mitochondrial membrane potential. ZnO-NPs further activated apoptotic cell death via the caspase cascades. Importantly, anti-oxidant and caspase inhibitor clearly prevented ZnO-NP-induced cell death, indicating the fact that superoxide-induced mitochondrial dysfunction is associated with the ZnO-NP-mediated caspase-dependent apoptosis in human GSCC. Moreover, ZnO-NPs significantly inhibited the phosphorylation of ribosomal protein S6 kinase (p70S6K kinase). In a corollary in vivo study, our results demonstrated that ZnO-NPs possessed an anti-cancer effect in a zebrafish xenograft model. Collectively, these results suggest that ZnO-NPs induce apoptosis through the mitochondrial oxidative damage and p70S6K signaling pathway in human GSCC. The present study may provide an experimental basis for ZnO-NPs to be considered as a promising novel anti­tumor agent for the treatment of gingival cancer.

Predictors for lower urinary tract symptoms and the urinary specific quality of life in prostate cancer patients: One-year follow-up.

BACKGROUND: Prostate cancer (PCa) is the most frequently diagnosed cancer and is becoming a growing concern in global epidemiology. Quality of life of patients has become a major outcome for cancer care but limited study investigated quality of life of PCa patients. Our study is to investigate predictors for treatment outcomes of lower urinary tract symptoms (LUTS), nocturia, and the urinary specific quality of life (uQoL) in PCa patients one year following treatment. METHODS: A prospective study of 131 consecutive patients was conducted with outcome measurements before treatment, at 3 months, 6 months, and one year following therapy. We utilized the International Prostate Symptom Score questionnaire to collect data. Generalized estimating equations were performed to identify predictors for major outcomes of LUTS, nocturia, and uQoL. RESULTS: LUTS increased slightly over time, but nocturia and uQoL were improved from baseline to 12 months. Results of the interaction analysis indicated that patients with TNM stage 3 compared with those with stage 2 had a reduction in LUTS from diagnosis to 6 months. Patients who received surgery or radiation compared to hormone therapy had worse nocturia from diagnosis to 6 months compared to those of patients who received hormone therapy. Higher body mass index (BMI) decreased the uQoL from diagnosis to 3 months, and higher prostate-specific antigen (PSA) level deteriorated the uQoL from diagnosis to 12 months. CONCLUSION: TNM stage and BMI affected the LUTS. Patients undergone a prostatectomy or radiation therapy showed more frequency of nocturia, BMI and PSA were also risk factors for nocturia. Moreover, patients' age, BMI, and PSA affected uQoL. In such patients, we recommend close monitoring of patients' specific characteristics such as TNM stage, BMI, and PSA for a better quality of life.

Tanshinone IIA inhibits angiogenesis in human endothelial progenitor cells in vitro and in vivo.

Accumulating evidence reports that bone marrow-derived endothelial progenitor cells (EPCs) regulate angiogenesis, postnatal neovascularization and tumor metastasis. It has been suggested that understanding the molecular targets and pharmacological functions of natural products is important for novel drug discovery. Tanshinone IIA is a major diterpene quinone compound isolated from Danshen (Salvia miltiorrhiza) and is widely used in traditional Chinese medicine (TCM). Evidence indicates that tanshinone IIA modulates angiogenic functions in human umbilical vein endothelial cells. However, the anti-angiogenic activity of tanshinone IIA in human EPCs has not been addressed. Here, we report that tanshinone IIA dramatically suppresses vascular endothelial growth factor (VEGF)-promoted migration and tube formation of human EPCs, without cytotoxic effects. We also show that tanshinone IIA markedly inhibits VEGF-induced angiogenesis in the chick embryo chorioallantoic membrane (CAM) model. Importantly, tanshinone IIA significantly attenuated microvessel formation and the expression of EPC-specific markers in the in vivo Matrigel plug assay in mice. Further, we found that tanshinone IIA inhibits EPC angiogenesis through the PLC, Akt and JNK signaling pathways. Our report is the first to reveal that tanshinone IIA reduces EPC angiogenesis both in vitro and in vivo. Tanshinone IIA is a promising natural product worthy of further development for the treatment of cancer and other angiogenesis-related pathologies.

Effectiveness of stress management in patients undergoing transrectal ultrasound-guided biopsy of the prostate.

BACKGROUND: To assess the utilization of stress management in relieving anxiety and pain among patients who undergo transrectal ultrasound (TRUS)-guided biopsy of the prostate. METHODS: Eighty-two patients admitted to a community hospital for a TRUS biopsy of the prostate participated in this case-controlled study. They were divided into an experimental group that was provided with stress management and a control group that received only routine nursing care. Stress management included music therapy and one-on-one simulation education. Before and after the TRUS biopsy, the patients' state-anxiety inventory score, pain visual analogue scale (VAS), respiratory rate, heart rate, and blood pressure were obtained. RESULTS: There were no differences in baseline and disease characteristics between the two groups. The VAS in both groups increased after the TRUS biopsy, but the difference in pre- and postbiopsy VAS scores was significantly lower in the experimental group (P=0.03). Patients in both groups experienced mild anxiety before and after the biopsy, but those in the experimental group displayed a significantly greater decrease in postbiopsy state-anxiety inventory score compared to the control group (P=0.02). CONCLUSION: Stress management can alleviate anxiety and pain in patients who received a TRUS biopsy of the prostate under local anesthesia.

Butein inhibits metastatic behavior in mouse melanoma cells through VEGF expression and translation-dependent signaling pathway regulation.

BACKGROUND: Melanoma is an aggressive skin cancer and a predominant cause of skin cancer-related deaths. A previous study has demonstrated the ability of butein to inhibit tumor proliferation and invasion. However, the anti-metastatic mechanisms and in vivo effects of butein have not been fully elucidated. METHODS: MTT cell viability assays were used to evaluate the antitumor effects of butein in vitro. Cytotoxic effects of butein were measured by lactate dehydrogenase assay. Anti-migratory effects of butein were evaluated by two-dimensional scratch and transwell migration assays. Signaling transduction and VEGF-releasing assays were measured by Western blotting and ELISA. We also conducted an experimental analysis of the metastatic potential of tumor cells injected into the tail vein of C57BL/6 mice. RESULTS: We first demonstrated the effect of butein on cell viability at non-cytotoxic concentrations (1, 3, and 10 µM). In vitro, butein was found to inhibit the migration of B16F10 cells in a concentration-dependent manner using transwell and scratch assays. Butein had a dose-dependent effect on focal adhesion kinase, Akt, and ERK phosphorylation in B16F10 cells. Butein efficiently inhibited the mTOR/p70S6K translational inhibition machinery and decreased the production of VEGF in B16F10 cells. Furthermore, the in vivo antitumor effects of butein were demonstrated using a pulmonary metastasis model. CONCLUSION: The results of the present study indicate the potential utility of butein in the treatment of melanoma.

Comparison of transrectal ultrasound-guided biopsy of the prostate and transurethral resection of the prostate for detection of prostate cancer in patients with moderate lower urinary tract symptoms.

BACKGROUND: To compare transrectal ultrasound (TRUS)-guided biopsy of the prostate and transurethral resection of the prostate (TURP) for detection of prostate cancer (PCa) in patients with moderate lower urinary tract symptoms (LUTS) by retrospective chart review. METHODS: Between January 2004 and December 2008, a total of 520 patients, aged 50.3-81.5 years, with moderate LUTS (International Prostate Symptom Score, 8-19), and elevation of prostate-specific antigen (≥ 4 ng/mL), or abnormal findings by digital rectal examination, were enrolled for evaluation. All the patients were recommended to receive TRUS-guided biopsy of the prostate (TRUS biopsy group) or TURP (TURP group) due to the possibility of PCa, according to their choice after full explanation by the doctors. RESULTS: There were 379 patients in the TRUS biopsy group and 141 in the TURP group. PCa was detected in 80 patients (21.1%) in the TRUS group and in 27 (19.1%) in the TURP group. Clinically localized PCa (T1-2N0M0) was found in 46 patients (57.5%) in the TRUS biopsy group and in 16 (59.3%) in the TURP group. Bone metastasis was noticed in 22 (27.5%) patients in the TRUS biopsy group and in 7 (25.9%) in the TURP group. The percentage of low-grade tumor was significantly higher in the TURP group than in the TRUS biopsy group (11.1% vs. 5%). CONCLUSION: TURP was not superior to TRUS-guided biopsy of the prostate for detection of PCa in patients with moderate LUTS and prostate-specific antigen ≥ 4 ng/mL.