CBX3 predicts an unfavorable prognosis and promotes tumorigenesis in osteosarcoma.

CBX3, namely chromobox protein homolog 3, a member of the heterochomatin protein 1 (HP1) family, has been shown to be associated with the tumorigenesis of various types of cancer. The aim of the present study was to assess the biological role and the clinicopathological importance of CBX3 in osteosarcoma. The Oncomine database was utilized to determine the CBX3 expression in sarcoma patients. A retrospective cohort study was conducted to evaluate the prognostic value of CBX3 expression. In addition, correlations between the clinicopathological features of the osteosarcoma patients and CBX3 expression were assessed and involved recurrence, distant metastasis, lymph node metastasis, response to chemotherapy, pathological differentiation, clinical stage, anatomic location, tumor size and age. To investigate the function of CBX3 in osteosarcoma, a small interfering RNA for CBX3 was designed and this was used for the transfection of osteosarcoma MG63 cells. Then, the effects of CBX3 on proliferation, cell cycle distribution and apoptosis of osteosarcoma cells were investigated via CCK­8 assay and cell cycle assay and cell apoptosis analysis, respectively. Based on our findings, upregulation of CBX3 expression was noted both in osteosarcoma and also other sarcoma types, which included pleomorphic liposarcoma, myxofibrosarcoma, myxoid/round cell liposarcoma and dedifferentiated liposarcoma. In addition, based on the retrospective cohort study, CBX3 expression was associated with the disease­free survival (DFS) and overall survival (OS) of the osteosarcoma patients and a large tumor size, high distant metastasis rate and high clinical stage rate. In addition, the proliferation ability was blocked by the knockdown of CBX3 through the application of CBX3 siRNA, and CBX3 knockdown also led to increased apoptosis and cell cycle arrest at G0 and G1 phases in osteosarcoma cells. CBX3 is highly expressed in human osteosarcoma tissues. Meanwhile, high CBX3 is a predictor of the poor prognosis of osteosarcoma patients. To conclude, the growth of osteosarcoma can be promoted by CBX3, which may be used as an independent potential prognostic biomarker for patients suffering from osteosarcoma.

Meta-analysis of the prognostic value of long non-coding RNA PVT1 for cancer patients.

BACKGROUND: Plasmacytoma variant translocation 1 (PVT1) is reported to be dysregulated in various cancers. Therefore, this meta-analysis was performed to clarify its utility as a prognosis marker in malignant tumors. METHODS: Electronic databases, including PubMed, OVID, Cochrane Library, and Web of Science databases, were retrieved from inception to December 16, 2017. Typically, hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated, so as to explore the relationship between PVT1 expression and patient survival. In addition, odds ratios (OR) were calculated to assess the association of PVT1 expression with pathological parameters. RESULTS: A total of 23 studies involving 2350 patients were included in this meta-analysis. The pooled HR suggested that high PVT1 expression levels were correlated with poor overall survival (OS, HR = 1.99, 95% CI: 1.73-2.28), disease-free survival (DFS, HR = 1.76, 95% CI: 1.45-2.14), and recurrence-free survival (RFS, HR = 1.74, 95% CI: 1.26-2.39) in cancer patients without obvious heterogeneity. Moreover, high PVT1 expression levels were also correlated with larger tumor size (OR = 1.47, 95% CI: 1.02-2.11), poor differentiation grade (OR = 1.79, 95% CI: 1.39-2.30), advanced tumor stage (pooled OR = 3.28, 95% CI: 2.46-4.38), lymph node metastasis (OR = 2.67, 95% CI: 1.66-4.29) and distant metastasis (OR = 4.00, 95% CI: 1.39-11.50) in cancer patients. CONCLUSIONS: Findings of this meta-analysis suggest that a high PVT1 expression level may serve as a novel biomarker of poor prognosis in cancers.

Enhanced Diffuse Reflectance and Microstructure Properties of Hybrid Titanium Dioxide Nanocomposite Coating.

In this research, we studied enhanced diffuse reflectance that can be achieved by excitations of multiple-scattering in a hybrid micro-structured titanium dioxide coating. Conventional approaches to obtain diffuse reflection structure rely heavily on exciting the scattering of randomly textured surface, whereas here, we reveal numerically and experimentally that, besides interface scattering, bulk scattering of ordered-disordered hybrid structure can be also employed to obtain highly efficient diffuse reflector. The diffuse reflectance over the measured wavelength region increases significantly with thickness, while angle and polarization-dependent specular reflections are suppressed. These results show the potential to be used as a highly efficient diffuse reflector or for applications in various advanced fields of photonics related to light extractions and diffusers.

PSA time to nadir as a prognostic factor of first-line docetaxel treatment in castration-resistant prostate cancer: evidence from patients in Northwestern China.

Docetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China; however, the prognostic factors associated with effects in these patients are still controversial. In this study, we retrospectively reviewed the data from 71 eligible Chinese patients who received docetaxel chemotherapy from 2009 to 2016 in our hospital and experienced a reduction of prostate-specific antigen (PSA) level ≥50% during the treatment and investigated the potential role of time to nadir (TTN) of PSA. TTN was defined as the time from start of chemotherapy to the nadir of PSA level during the treatment. Multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS). In these patients, the median of TTN was 17 weeks. Patients with TTN ≥17 weeks had a longer response time to chemotherapy compared to TTN <17 weeks (42.83 vs 21.50 weeks, P < 0.001). The time to PSA progression in patients with TTN ≥17 weeks was 11.44 weeks compared to 5.63 weeks when TTN was <17 weeks. We found several factors to be associated with OS, including TTN (hazard ratio [HR]: 3.937, 95% confidence interval [CI]: 1.502-10.309, P = 0.005), PSA level at the diagnosis of cancer (HR: 4.337, 95% CI: 1.616-11.645, P = 0.004), duration of initial androgen deprivation therapy (HR: 2.982, 95% CI: 1.104-8.045, P = 0.031), neutrophil-to-lymphocyte ratio (HR: 3.963, 95% CI: 1.380-11.384, P = 0.011), and total PSA response (Class 1 [<0 response] compared to Class 2 [0-50% response], HR: 3.978, 95% CI: 1.278-12.387, P = 0.017). In conclusion, TTN of PSA remains an important prognostic marker in predicting therapeutic outcome in Chinese population who receive chemotherapy for mCRPC and have >50% PSA remission.

MiR-1246 Promotes LPS-Induced Inflammatory Injury in Chondrogenic Cells ATDC5 by Targeting HNF4γ.

BACKGROUND/AIMS: Osteoarthritis (OA) is a common inflammatory joint disease. miRNAs are associated with OA and functionally implicated in the pathogenesis of the disease. In the present study, we investigated the role of miR-1246 in the lipopolysaccharide (LPS)-induced inflammatory injury of ATDC5 cells. METHODS: ATDC5 cells were cultured and treated with LPS in a series of concentration (0, 1, 5, and 10 µg/ml) for 5 h. The cells were transfected with miR-1246-mimic, inhibitor, si-HNF4γ or negative control, then were assessed for cell viability using CCK8 assay, apoptosis by flow-cytometry and expressions of miR-1246 and pro-inflammatory cytokines by qRT-PCR and western blot analysis. RESULTS: Cell viability was significantly reduced and cell apoptosis was added in ATDC5 cells injured with LPS at the dosage of 5 and 10 µg/ml. Relative mRNA expressions of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8 and TNF-α) were significantly increased. miR-1246 was up-regulated in ATDC5 cells treated with LPS. Moreover, miR-1246 overexpression aggravated LPS-induced decrease in cell viability, increase in apoptosis and overproduction of pro-inflammatory factors. mRNA and protein expressions of HNF4γ were significantly suppressed in cells transfected with miR-124-mimic. Further, miR-1246 knockdown alleviated LPS-induced inflammatory injury by up-regulating the expression of HNF4γ and activation of PI3K/AKT and JAK/STAT pathways. CONCLUSIONS: Suppression of miR-1246 alleviated LPS-induced inflammatory injury in chondrogenic ADTC5 cells by up-regulation of HNF4γ and activation of PI3K/AKT and JAK/STAT pathways. The findings of this study will provide a novel viewpoint regarding miR-1246 target for clinical.

Solasodine inhibits human colorectal cancer cells through suppression of the AKT/glycogen synthase kinase-3ß/ß-catenin pathway.

Solasodine is a main active component isolated from Solanum incanum L. that performs a wide range of functions containing anti-oxidant, anti-infection, and neurogenesis promotion. In this study, we explored the influence of solasodine on three types of human colorectal cancer (CRC) cell lines. The results show that solasodine prohibited CRC cell proliferation dose- and time-dependently and impeded CRC cell motility by downregulating MMPs. Solasodine was also found to fuel caspase-cascade reaction and increase the ratio between Bax and Bcl-2 so as to induce CRC cell apoptosis. When cells were pretreated with AKT activator (insulin-like growth factor-1) followed by solasodine, the solasodine-induced apoptosis was partially abrogated by insulin-like growth factor-1. Moreover, solasodine hindered tumor development and stimulated similar mechanisms in vivo. In general, our study provides the first evidence that solasodine has a suppressive effect on CRC cells and that this agent may be a novel therapeutic drug for CRC treatment.

Prognostic factors of first-line docetaxel treatment in castration-resistant prostate cancer: roles of neutrophil-to-lymphocyte ratio in patients from Northwestern China.

OBJECTIVE: To evaluate the potential role of neutrophil-to-lymphocyte ratio (NLR) with therapeutic response in patients who were treated with docetaxel for mCRPC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data from 111 consecutive patients who were treated with docetaxel for mCRPC from 2009 to 2016 in a single center from Northwestern China. Pretreatment baseline and follow-up data including age, PSA response, Gleason score, and cycle number were reviewed, and multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS) and progression-free survival (PFS). RESULTS: In Kaplan-Meier analyses, the NLR (optimal threshold 3.3), total PSA response, number of chemotherapy cycles, stage T, baseline of PSA, albumin, presence of visceral metastases, and PSA level at the diagnosis of cancer were significantly associated with OS, respectively. In multivariable analyses, higher NLR (>3.3), PSA level at the diagnosis of cancer (≥162 ng/ml), number of chemotherapy cycles, and albumin (<40.5 g/l) were associated with increased risk of death, respectively. Meanwhile, young age, higher NLR, number of chemotherapy cycles, presence of visceral metastases, and poor PSA response were associated with shorter PFS. CONCLUSION: NLR combined with PSA level at the diagnosis of cancer remains an important prognostic marker in predicting therapeutic outcome in Chinese men who receive chemotherapy for mCRPC.

[Efficacy and tolerability of dapoxetine in the treatment of premature ejaculation].

OBJECTIVE: To investigate the efficacy and adverse effects of dapoxetine in the treatment of premature ejaculation. METHODS: We randomly assigned outpatients with premature ejaculation in the proportion of 2:1 to receive 30 mg dapoxetine on demand (n =78) or 50 mg sertraline qd for one month (n = 39). Follow-up was accomplished in 95 cases, 63 in the dapoxetine group and 32 in the sertraline group. We recorded the intravaginal ejaculatory latency time (IELT), clinical global impression of change (CGIC) score, and adverse reactions of the patients and compared them between the two groups. RESULTS: IELT was significantly increased in both the dapoxetine (from [0.87 ± 0.31] to [2.84 ± 0.68] min, P < 0.05) and the sertraline group (from [0.84 ± 0.28] to [2.71 ± 0.92] min, P < 0.05) after medication. Based on the CGIC scores in premature ejaculation, the rate of excellence or effectiveness was 36.5% in the dapoxetine and 37. 5% in the sertraline group, and the rate of improvement was 63.5% in the former and 71.9% in the latter. The incidence rates of dizziness, nausea, headache, and diarrhea were slightly higher (P > 0.05) while those of fatigue, somnolence, and dry mouth significantly higher (P < 0.05) in the sertraline than in the dapoxetine group. CONCLUSION: On-demand oral medication of dapoxetine is effective and well-tolerated for the treatment of premature ejaculation.

[Effect of down-regulation of histone deacetylase 2 protein expression on cell proliferation and cell cycle in cervical carcinoma].

OBJECTIVE: To study the effect of down-regulation of histone deacetylase 2 (HDAC2) expression on cell proliferation and cell cycle in cervical carcinoma cell lines HeLa. METHODS: HDAC2 siRNA and control siRNA were transfected to HeLa cells. CCK-8 and flow cytometry were used to analyze the changes of cell proliferation and cell cycle, respectively. Western blot was employed to detect the changes of cell proliferation and cell cycle-related proteins. RESULTS: HDAC2 siRNA significantly down-regulated the expression of HDAC2 protein in HeLa cells, resulting in marked inhibition of cell proliferation. In addition, the percentage of cells in G(0)/G(1) phase in HDAC2 siRNA group (63.3% ± 2.0%) was significantly higher than that in untreated group (29.3% ± 1.7%) or control siRNA group (29.4% ± 1.7%), F = 354.181, P = 0.000. Furthermore, Western blot demonstrated that down-regulation of HDAC2 expression decreased the expression of cyclin D1, cyclin E and CDK2 proteins but increased the expression of p21 protein. CONCLUSIONS: Down-regulation of HDAC2 expression mediates proliferation inhibition and cell cycle arrest. It is associated with decrease in cyclin D1, cyclin E and CDK2 protein expression and increase in p21 protein expression.

Differentiations of transplanted mouse spermatogonial stem cells in the adult mouse renal parenchyma in vivo.

AIM: Spermatogonial stem cells can initiate the process of cellular differentiation to generate mature spermatozoa, but whether it possess the characteristic of pluripotency and plasticity, similar to embryonic stem cells, has not been elucidated. This study was designed to evaluate the differentiation potential of spermatogonial stem cells into renal cells in vivo. METHODS: Neonatal mouse spermatogonial stem cells were transplanted into mature male mice lacking endogenous spermatogenesis. The restoration of fertility in recipient males was observed. Spermatogonial stem cells were then injected into renal parenchyma of mature female mice to make a new extracellular environment for differentiation. Fluorescence in situ hybridization technology (FISH) was used to detect the expression of chromosome Y in recipient renal tissues. To determine the type of cells differentiated from spermatogonial stem cells, the expression of ricinus communis agglutinin, vimentin, CD45, and F(4/80) proteins were examined in the renal tissues by immunohistochemistry. RESULTS: The proliferation of seminiferous epithelial cells was distinctly observed in seminiferous tubules of transplanted testes, whereas no regeneration of spermatogenesis was observed in non-transplanted control testes. In transplanted female renal tissues, FISH showed a much stronger immuno-fluorescence signal of chromosome Y in the nucleolus of epithelial cells of the renal tubule and podocytes of the glomerulus. CONCLUSION: The spermatogonial stem cells were successfully purified from mouse testicles. This finding demonstrated that spermatogonial stem cells could not only restore damaged spermatogenesis, but were also capable of differentiating into mature renal parenchyma cells in vivo.

A novel anti-cancer effect of genistein: reversal of epithelial mesenchymal transition in prostate cancer cells.

AIM: The aim of the present study was to investigate whether low dose genistein affects the invasion and epithelial mesenchymal transition (EMT) of prostate cancer (PCa) cells. METHODS: Human PCa cell lines, IA8-ARCaP and LNCaP/ HIF-1a, were used in this study. The cell lines were found to process EMT in our previous study. The PCa cells were treated with increasing concentrations, from 0.1 to 75 micromol/L. Proliferation was assessed with 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay. EMT was proven by cell morphological transition and the expression changes of EMT-related markers, which were confirmed by RT-PCR, Western blotting, and indirect immunofluorescence labeling. Transwell invasion assay was used to analyze the invasive potency. RESULTS: The addition of genistein to the medium reduced the IA8-ARCaP and LNCaP/HIF-1a viable cell number in a dose-dependent manner (with increasing concentrations from 15 to 75 micromol/L). Less than 15 micromol/L genistein was selected as the low dose concentration, which did not affect cell proliferation. The treatment of cells with low-dose genistein induced the reversal of EMT, which was confirmed by cell morphological transition and the expression changes of EMT-related markers. The reversal of EMT in the PCa cells by low-dose genistein was in a dose-dependent manner. Moreover, low-dose genistein effectively inhibited invasion of the PCa cells in vitro. CONCLUSION: These results showed that treatment with low-dose genistein may be a potential strategy for the suppression of invasive growth through the reversal of EMT in cancer cells, which justifies the potential use of soybean foods as a practical chemopreventive approach for patients with PCa.

[Papillary cystadenocarcinoma in a Müllerian duct cyst: report of a case with literature review].

OBJECTIVE: To study the diagnosis and treatment of Müllerian duct cysts and their involvement with malignancy. METHODS: A 44-year-old male patient with papillary cystadenocarcinoma involving a Müllerian duct cyst was presented. The presentation treatment, and pathological and radiological appearances were retrospectively analysed and discussed with literature review. The main manifestation was intermittent episode of hemospermia accompanying terminal hematuria and infertility for 15 years. Final diagnosis was determined by the findings of transrectal ultrasound scan, CT scan, MRI imaging, cystoscopic examination and biopsy. RESULTS: Exploratory laparotomy was performed through a suprapubic retrovesical approach. The finding that a duct-like wedge of tumor tissue passed through the prostate near cyst neck to the posterior urethra without affecting the adjacent prostatic tissue during tylectomy confirmed that it arises from Müllerian duct system. Pathohistologic examination disclosed a papillary cystadenocarcinoma and it infiltrated the wall of the cyst. Both seminal vesicles and ejaculatory duct had no carcinoma invasion. CONCLUSION: Müllerian duct cyst involving with malignancy is exceedingly rare, the diagnosis is based on the findings of transrectal ultrasound scan, CT scan, MRI imaging, cystoscopic examination. The final diagnosis depends on the pathohistologic examination. Lumpectomy is effective and have a good outcome.