Inducing apoptosis is a promising therapeutic approach to overcome cancer. Here we described that a novel synthesized compound, 3-amino-N-(4-chlorobenzyl)-6-(3-methoxyphenyl)thieno[2,3-b]pyridine-2-carboxamide (SKLB703), exhibits antitumor activity via inducing apoptosis both invitro and invivo. Our results showed that SKLB703 inhibited the proliferation of a panel of human cancer cell lines, and human hepatocellular carcinoma cell line HepG2 was the most sensitive. The proliferation inhibitory effect of SKLB703 was associated with its apoptosis-inducing effect by activating caspase-3 and caspase-9 rather than caspase 8. Exposure of HepG2 to SKLB703 also resulted in Bax upregulation, Bcl-2 downregulation, cytochrome c release and mitochondrial transmembrane potential change in mitochondrial apoptotic pathway. Moreover, the decrease of phosphorylated p 44/42 mitogen-activated protein kinase and phosphorylated Akt was observed. SKLB703 suppressed the growth of established tumors in xenograft models in mice, whereas no toxicity was exhibited. TUNAL analysis showed that SKLB703 induced HepG2 tumor apoptosis. Taken together, the present study demonstrates that SKLB730 exhibits its antitumor activity through inducing apoptosis via mitochondrial apoptotic pathway. Its potential to be a candidate of anticancer agent is worth being further investigated. 相似文献
Serous ovarian cancer is the most frequent type of epithelial ovarian cancer. Despite the use of surgery and platinum‐based chemotherapy, many patients suffer from recurrence within 6 months, termed platinum resistance. Currently, the lack of relevant molecular biomarkers for the prediction of the early recurrence of serous ovarian cancers is linked to the poor prognosis. To identify an effective biomarker for early recurrence, we analyzed the genome‐wide DNA methylation status characteristic of early recurrence after treatment. The patients in The Cancer Genome Atlas (TCGA) dataset who showed a complete response after the first therapy were categorized into 2 groups: early recurrence serous ovarian cancer (ERS, recurrence ≤12 months, n = 51) and late recurrence serous ovarian cancer (LRS, recurrence >12 months, n = 158). Among the 12 differently methylated probes identified between the 2 groups, we found that ZNF671 was the most significantly methylated gene in the early recurrence group. A validation cohort of 78 serous ovarian cancers showed that patients with ZNF671 DNA methylation had a worse prognosis (P <.05). The multivariate analysis revealed that the methylation status of ZNF671 was an independent factor for predicting the recurrence of serous ovarian cancer patients both in the TCGA dataset and our cohort (P =.049 and P =.021, respectively). Functional analysis revealed that the depletion of ZNF671 expression conferred a more migratory and invasive phenotype to the ovarian cancer cells. Our data indicate that ZNF671 functions as a tumor suppressor in ovarian cancer and that the DNA methylation status of ZNF671 might be an effective biomarker for the recurrence of serous ovarian cancer after platinum‐based adjuvant chemotherapy. 相似文献
The purpose of this study was to evaluate the structure and function of the meibomian gland and the incomplete blinking rate to understand the pathophysiology of dry eye in thyroid eye disease (TED) patients.
Methods
Patients who were diagnosed with TED were enrolled between October 2015 and February 2016. Clinical measurements were performed in the following order: (i) external examination (Hertel exophthalmometer and palpebral fissure height), (ii) LipiView interferometer (lipid layer thickness [LLT], incomplete blinking rate, and meibography), (iii) slit-lamp biomicroscopy (corneal surface staining, tear breakup time, meibum expression, Marx line).
Results
Thirty eyes of 30 TED patients (male = 8; female = 22) were included in this study. The TED patient population had a mean age of 42.9 ± 11.8 years and a mean clinical activity score (CAS) of 2.33 ± 1.60. The meiboscore was 1.17 ± 0.90 in the upper eyelid and 0.70 ± 0.65 in the lower eyelid; scores were significantly higher in the upper eyelid (p < 0.001). The mean LLT was 82.43 ± 24.52 nm, and the mean incomplete blinking rate was 51.04 ± 33.62% (0–100%). CAS was the only variable that correlated with the meiboscore. There was no significant correlation between incomplete blinking and a degree of palpebral fissure height or proptosis.
Conclusions
Tear film instability due to increased incomplete blinking can cause dry eye in TED. In addition to the increase in CAS, meibomian gland dysfunction may also be a cause of dry eye in TED. However, further comparative studies are needed to confirm these results. 相似文献
Objectives: Genome-wide association studies (GWAS) followed by independent replications suggest that ZNF804A is a risk gene for schizophrenia (SCZ), considering the substantial genetic overlap between SCZ and major mood disorders (e.g., bipolar disorder (BPD) and major depressive disorder (MDD)).
Methods: We collected the data of two ZNF804A single-nucleotide polymorphisms (SNPs rs1344706 and rs7597593) from European and Asian populations to perform systematic meta-analyses with major mood disorders in a total of 65,240 subjects.
Results: Meta-analysis showed that rs1344706 and rs7597593 were both associated with major mood disorders as well as diagnosis of either BPD or MDD, although neither of the analyses achieved a genome-wide level of statistical significance.
Conclusions: Our data provide evidence for the genetic involvement of ZNF804A SNPs in the susceptibility of major mood disorders, but further replication analyses in larger samples are necessary. 相似文献
Imaging studies have demonstrated that prefrontal and parietal regions are activated during working memory (WM) tasks. Recently some molecular genetic studies reported associations between a functional promoter polymorphism of the tryptophan hydroxylase 2 gene (TPH2), that regulates the synthesis of serotonin, and attention. In 49 healthy Caucasian subjects the role of the TPH2 -703 G/T polymorphism for WM was tested by means of an imaging genomics approach in an n-back task. fMRI data showed an increased activation for the 2-back as compared to the 0-back condition for a large network in prefrontal and parietal areas. Although behavioural data showed no performance differences between the genotype groups of the -703 G/T a significantly stronger activation of the TT genotype carriers in BA 6, BA 46, and BA 40 was visible in contrast to the GT and GG groups. Present findings in congruence with previous findings support the hypothesis that TT carriers compensate deficits in executive control functions by increased brain activity. 相似文献