Targeted therapy for intractable cancer on the basis of molecular profiles: An open-label, phase II basket trial (Long March Pathway).

Purpose: We evaluated he effects of molecular guided-targeted therapy for intractable cancer. Also, the epidemiology of druggable gene alterations in Chinese population was investigated. Materials and methods: The Long March Pathway (ClinicalTrials.gov identifier: NCT03239015) is a non-randomized, open-label, phase II trial consisting of several basket studies examining the molecular profiles of intractable cancers in the Chinese population. The trial aimed to 1) evaluate the efficacy of targeted therapy for intractable cancer and 2) identify the molecular epidemiology of the tier II gene alterations among Chinese pan-cancer patients. Results: In the first stage, molecular profiles of 520 intractable pan-cancer patients were identified, and 115 patients were identified to have tier II gene alterations. Then, 27 of these 115 patients received targeted therapy based on molecular profiles. The overall response rate (ORR) was 29.6% (8/27), and the disease control rate (DCR) was 44.4% (12/27). The median duration of response (DOR) was 4.80 months (95% CI, 3.33-27.2), and median progression-free survival (PFS) was 4.67 months (95% CI, 2.33-9.50). In the second stage, molecular epidemiology of 17,841 Chinese pan-cancer patients demonstrated that the frequency of tier II gene alterations across cancer types is 17.7%. Bladder cancer had the most tier-II alterations (26.1%), followed by breast cancer (22.4%), and non-small cell lung cancer (NSCLC; 20.2%). Conclusion: The Long March Pathway trial demonstrated a significant clinical benefit for intractable cancer from molecular-guided targeted therapy in the Chinese population. The frequency of tier II gene alterations across cancer types supports the feasibility of molecular-guided targeted therapy under basket trials.

Ornidazole Reduces the Progression of Endometriosis in a Rat Model.

OBJECTIVE: The aim of this study was to investigate the effectiveness of ornidazole in inhibiting the progression of endometriosis in a rat model. DESIGN: This was an in vivo experiment, including the ornidazole group (n = 16) and a control group (n = 14). Rats were provided with free access to water containing ornidazole (1 g/L) or drinking water only for 14 days. MATERIALS AND METHODS: Surgical induction of endometriosis was performed in Sprague Dawley rats via autologous endometrial transplantation. Rats were provided with free access to water containing ornidazole (1 g/L) or drinking water only for 14 days. Once the rats were euthanized (ornidazole group, n = 16; control group, n = 14), histological signatures and the volumes of endometriosis lesions were assessed. Cells positive for the inflammatory cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α were counted. Angiogenesis was identified by assessing vascular endothelial growth factor (VEGF) and microvessel density. RESULTS: The median lesion volume was lower in the ornidazole group (20.2 mm3; range, 5.7-53.3 mm3) than in the control group (81.3 mm3; range, 32.8-122.2 mm3; p = 0.007). Median IL-1ß cell counts were 5.3 (range, 4.5-6.4) for ornidazole and 11.7 (range, 9.4-15.4) for control (p < 0.001). Mean IL-6 cell counts were 5.6 ± 1.8 for ornidazole and 11.3 ± 4.1 for control (p < 0.001). Median TNF-α cell counts were 5.7 (range, 4.5-7.2) for ornidazole and 12.1 (range, 10.0-15.9) for control (p < 0.001). Median VEGF cell counts were 8.1 (range, 6.5-11.4) for ornidazole and 18.3 (range, 14.2-21.0) for control (p = 0.001). Median microvessel density values were 11.3/HPF (range, 7.7-21.8) for ornidazole and 28.7/HPF (range, 13.1-48.2) for control (p = 0.012). LIMITATIONS: This study is a short period and small sample size experiment. In this study, multiple drug concentrations were not used. We did not use in vitro models to assess the anti-inflammatory and antiangiogenic effects of ornidazole on endometriosis, and the specific anti-inflammatory and antiangiogenic mechanisms associated with ornidazole need to be further investigated. CONCLUSION: Ornidazole restricts the growth of endometriosis in rats, possibly by exerting anti-inflammatory and antiangiogenic effects.

Estradiol mediates the interaction of LINC01541 and miR-429 to promote angiogenesis of G1/G2 endometrioid adenocarcinoma in-vitro: A pilot study.

Background: Endometrioid adenocarcinoma (EAC) is the most common subtype of endometrial cancer (EC) and is an estrogen-related cancer. In this study, we sought to investigate the expressions and mechanism of action of 17ß-estradiol (E2) and long noncoding RNA (lncRNA) LINC01541 in G1/G2 EAC samples. Methods: The expressions of estrogen receptor ß (ESR2), LINC01541, miR-200s, and VEGFA were evaluated using real-time PCR in human EAC tissues (n = 8) and adjacent normal tissues (n = 8). Two EC cell lines (Ishikawa and RL95-2) were selected for validation in vitro. Bioinformatics analyses and luciferase reporter analyses were performed to verify potential binding sites. qRT-PCR, Western blot, and CCK-8 were used to identify the regulatory mechanisms of related genes in cell biological behavior. Results: Compared with adjacent normal tissues, LINC01541 and miR-200s family (except miR-200c) were highly expressed in EAC tissues (n=8), while ESR2 and VEGFA were lowly expressed in EAC tissues (* P < 0.05; ** P < 0.01). In vitro: E2 inhibited the expression of LINC01541 and miR-429 in both cell lines, and estrogen antagonist (PHTPP) could reverse this effect, in addition, PHTPP could promote the proliferation of these two cancer cells, cell transfection LINC01541 also had this effect after overexpression of plasmid and miR-429 mimic. E2 promotes the expression of VEGFA in both cell lines, and PHTPP can also reverse this effect. LINC01541 interacts with miR-429 to promote the expression of each other, and both inhibit the synthesis of VEGFA in EAC cells after overexpression. Through the double validation of bioinformatics analysis and dual fluorescein reporter gene, it was confirmed that miR-429 targets the regulation of VEGFA expression (* P < 0.05; ** P < 0.01). Conclusion: E2 promotes the synthesis of VEGFA by altering the expression levels of LINC01541 and miR-429 in EAC, thereby affecting the angiogenesis process of EAC. Also, E2-mediated LINC01541/miR-429 expression may affect cell migration in EAC. In addition, we identified a reciprocal promotion between LINC01541 and miR-429.

Use of apatinib combined with pemetrexed for advanced ovarian cancer: A case report.

INTRODUCTION: Ovarian cancer is the most deadly gynecologic cancer, and the therapy is very difficult. Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2. At present, there are few studies or case reports on apatinib treatment for patients with ovarian cancer. CASE PRESENTATION: A 75-year-old Chinese woman had a medical history of ovarian high-grade serous papillary adenocarcinoma, who got many lines of chemotherapy and apatinib-an antiangiogenesis drug therapy. Either alone or in combination, apatinib may extend the survival time of patients with advanced ovarian cancer. CONCLUSION: Apatinib may be an option for advanced ovarian cancer after failure of chemotherapy or other targeted therapy. The role of apatinib in the treatment of advanced ovarian cancer needs further study.

A potential link between polycystic ovary syndrome and non-alcoholic fatty liver disease: an update meta-analysis.

BACKGROUND: Epidemiological literature regarding the effect of polycystic ovary syndrome (PCOS) as a risk factor for non-alcoholic fatty liver disease (NAFLD) remains inconsistent. Furthermore, it remains debatable whether NAFLD is associated with PCOS as a consequence of shared risk factors or whether PCOS contributes to NAFLD in an independent fashion. Therefore, this meta-analysis was conducted. METHODS: This meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Relevant studies published before May 2017 were identified and retrieved from PubMed and Web of Science databases. The data were extracted, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: A total of 17 studies were included into the present analysis. Compared to the control group, the risk of NAFLD in the PCOS group was higher (OR = 2.25, 95% CI = 1.95-2.60). When stratified by BMI and geographic location, the results indicated that the frequency of NAFLD risk was significantly higher in obese subjects (OR = 3.01, 95% CI = 1.88-4.82), non-obese subjects (OR = 2.07, 95% CI = 1.12-3.85), subjects from Europe (OR = 2.00, 95% CI = 1.58-2.52), subjects from the Asia-Pacific Region, (OR = 2.32, 95% CI = 1.89-2.84) and subjects from America (OR = 2.96, 95% CI = 1.93-4.55). In addition, PCOS patients with hyperandrogenism (HA) had a significantly higher risk of NAFLD, compared with controls (OR = 3.31, 95% CI = 2.58-4.24). However, there was no association between PCOS patients without HA and higher risk of NAFLD (OR = 1.46; 95% CI =0.55-3.87). The results of this meta-analysis should be interpreted with caution due to the small number of observational studies and possible confounding factors. CONCLUSION: The meta-analysis results suggest that PCOS is significantly associated with high risk of NAFLD. Although this association was independent of obesity and geographic region, it might be correlated with HA.

Ambient air pollution and congenital heart defects in Lanzhou, China.

Congenital heart defects are the most prevalent type of birth defects. The association of air pollution with congenital heart defects is not well understood. We investigated a cohort of 8,969 singleton live births in Lanzhou, China during 2010-2012. Using inverse distance weighting, maternal exposures to particulate matter with diameter ≤10µm (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were estimated as a combination of monitoring station levels for the time spent at home and the work location. We used logistic regression to estimate the associations, adjusting for maternal age, education, income, BMI, disease, folic acid intake and therapeutic drug use, and smoking; season of conception; fuels for cooking; and temperature. We found significant positive associations of Patent Ductus Arteriosus (PDA) with PM10 during the 1st trimester, 2nd trimester and the entire pregnancy (OR 1st trimester=3.96, 95% Confidence Interval (CI): 1.36, 11.53; OR 2nd trimester=3.59, 95% Confidence Interval (CI): 1.57, 8.22; OR entire pregnancy=2.09, 95% CI: 1.21, 3.62, per interquartile range (IQR) increment for PM10 (IQR=71.2, 61.6, and 27.4 µg/m3 respectively)), and associations with NO2 during 2nd trimester and entire pregnancy (OR 2nd trimester= 1.92, 95% CI: 1.11, 3.34; OR entire pregnancy=2.32, 95% Cl: 1.14, 4.71, per IQR increment for NO2 (IQR=13.4 and 10.9 µg/m3 respectively)). The associations for congenital malformations of the great arteries and pooled cases showed consistent patterns. We also found positive associations for congenital malformations of cardiac septa with PM10 exposures in the 2nd trimester and the entire pregnancy, and SO2 exposures in the entire pregnancy. Results indicate a health burden from maternal exposures to air pollution, with increased risk of congenital heart defects.

Passive smoking and preterm birth in urban China.

Studies investigating the relationship between maternal passive smoking and the risk of preterm birth have reached inconsistent conclusions. A birth cohort study that included 10,095 nonsmoking women who delivered a singleton live birth was carried out in Lanzhou, China, between 2010 and 2012. Exposure to passive smoking during pregnancy was associated with an increased risk of very preterm birth (<32 completed weeks of gestation; odds ratio = 1.98, 95% confidence interval: 1.41, 2.76) but not moderate preterm birth (32-36 completed weeks of gestation; odds ratio = 0.98, 95% confidence interval: 0.81, 1.19). Risk of very preterm birth increased with the duration of exposure (P for trend = 0.0014). There was no variability in exposures by trimester. The associations were consistent for both medically indicated and spontaneous preterm births. Overall, our findings support a positive association between passive smoking and the risk of very preterm birth.