Introduction: Cyclin D1 (D1) binds to cyclin-dependent kinases (CDK) 4 or 6 to form a holoenzyme that phosphorylates the Rb protein to promote cell cycle progression from G1 to S phase. Therefore, targeting CDK4/6 may be a good strategy for chemotherapy of cancer. We performed a proof-of-principle study to determine the effect of Naphtho [2, 1-α] pyrrolo [3, 4-c] carbazole-5, 7 (6H, 12H)-dione (NPCD), a novel CDK4 inhibitor, on breast cancer cell lines.Methods: NPCD was synthesized and purified to over 99% purity verified by HPLC. MCF7, MB231, MCF15, T47D and GI101Ap human breast cancer cells were analyzed for the efficacy of NPCD with MTT and clonogenic assays, with FACS and staining for ethidium bromide and acridine orange for cell death and cell cycle profile. Western blot, reverse transcription and PCR were used for studies of gene expression, and co-immunoprecipitation for protein-complex formation.Results: MTT assay showed that NPCD caused growth arrest and apoptosis of MCF7, MDA-MB231, T47D, MCF15 and GI101Ap cells with an IC50 ranging between 3 to 8 µM given as a single dose. The growth arrest persisted for many days after cessation of the treatment, as shown in a clonogenic assay. NPCD could induce or reduce the D1 and CDK4 protein levels, depending on the cell line, but this effect was not correlated with its efficacy. Phosphorylation of D1 at Thr286 was decreased but it unexpectedly did not correlate with the change in D1 level in the cell lines studied. Phosphorylation of the Rb protein was decreased as expected whereas the p27kip1 protein level was decreased unexpectedly. Protein levels of p21cip1, CDK2 and cyclin E were also decreased in some, but not all, of the cell lines, whereas the mRNA levels of D1, CDK4, cyclin E, CDK2, p27kip1 and p21cip1 were increased in different cell lines.Conclusions: NPCD can cause long-lasting growth arrest and cell death of breast cancer cell lines at an IC50 of 3-8 µM. Decreased phosphorylation of Rb by D1-CDK4/6 and decreased p27kip1 protein level may be part of the underlying mechanism.

To assess the clinicopathological significance of survivin in ovarian carcinoma through this meta-analysis. PubMed, EMBASE, Web of Science, and The Cochrane Library databases were searched for relevant studies published through September, 2017. Included studies reported the case-control study of surviving expression with ovarian cancer and its clinicopathological characteristics. The quality assessment was performed according to the Newcastle–Ottawa Scale (NOS) for quality assessment of case–control studies. Statistical analysis was performed with the software Stata 12.0. Twelve eligible studies with a total of 1097 patients were included in this meta-analysis. Survivin overexpression was closely related to FIGO stage (I-II vs. III-IV) of ovarian carcinoma (odds ratio [OR] = 0.26,95% confidence interval [CI]:0.16,0.42),P<0.00001),tumor grade (G1-G2 vs. G3) (OR = 0.29,95%CI(0.17, 0.51),P <0.0001), but was not significantly associated with lymphatic metastasis (OR = 1.53, 95%CI(0.77, 3.03, P = 0.23),ascites (OR = 0.89,95%CI(0.39,2.05),P = 0.79). Our meta-analysis shows that survivin is strongly associated with FIGO stage and tumor grade of ovarian carcinoma. Maybe survivin is a novel clinicopathological marker of ovarian carcinoma.

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Systematic investigation with large sample size of the distribution of etiologies of renal artery stenosis (RAS) is scant in both Western countries and China. We retrospectively analyzed the etiology of RAS in 2047 consecutive inpatients diagnosed with RAS for hypertension at Fuwai Hospital between 1999 and 2014. The number of patients with atherosclerosis was 1668 (81.5%), 259 (12.7%) with Takayasu's arteritis (TA), 86 (4.2%) with fibromuscular dysplasia (FMD), 34 (1.6%) with other causes. There was an obvious increase with age in the proportion of atherosclerotic RAS (P<0.001). In patients aged ⩽40 years (n=319) the predominant etiology of RAS was TA (60.5%), followed by FMD (24.8%). In patients aged >40 years (n=1728) the major cause of RAS was atherosclerosis (94.7%), followed by TA (3.8%).The proportion of TA and FMD in female patients was significantly higher than that in male patients (P<0.001). In female patients aged ⩽40 years (n=215), the top three etiologies of RAS were TA (68.4%), FMD (27.9%) and atherosclerosis (1.4%). The present analysis showed that atherosclerosis, TA and FMD were sequentially the top three causes of RAS in the National Center of China. Age and gender had a significant effect on the distribution of etiologies of RAS.