Cisplatin resistance remains one of the major obstacles when treating epithelial
ovarian cancer. Because oxaliplatin and nedaplatin are effective against
cisplatin-resistant ovarian cancer in clinical trials and signal transducer and
activator of transcription 3 (STAT3) is associated with cisplatin resistance, we
investigated whether overcoming cisplatin resistance by oxaliplatin and nedaplatin
was associated with the STAT3 pathway in ovarian cancer. Alamar blue, clonogenic, and
wound healing assays, and Western blot analysis were used to compare the effects of
platinum drugs in SKOV-3 cells. At an equitoxic dose, oxaliplatin and nedaplatin
exhibited similar inhibitory effects on colony-forming ability and greater inhibition
on cell motility than cisplatin in ovarian cancer. Early in the time course of drug
administration, cisplatin increased the expression of pSTAT3 (Tyr705), STAT3α, VEGF,
survivin, and Bcl-XL, while oxaliplatin and nedaplatin exhibited the
opposite effects, and upregulated pSTAT3 (Ser727) and STAT3β. The STAT3 pathway
responded early to platinum drugs associated with cisplatin resistance in epithelial
ovarian cancer and provided a rationale for new therapeutic strategies to reverse
cisplatin resistance.
BackgroundThe aim of this study was to explore the relationships of HPIP expression status with the clinicopathological variables and survival outcomes of patients with cervical cancer (CC).MethodsWe compared the HPIP expression of 119 samples from CC tissues, 20 from cervical intraepithelial tissues, and 20 from normal cervical tissues by using immunohistochemical staining.ResultsIt was observed that the ratio of elevated HPIP expression was higher in CC tissues than in cervical intraepithelial neoplasia (P=0.017) and normal cervical tissues (P=0.001). In addition, there was an association between HPIP and clinicopathological factors, such as histological grade (P<0.001), stromal infiltration (P=0.015), lymph node metastasis (P<0.001), lymphovascular space invasion (LVSI; P=0.026), and recurrence (P=0.029). Furthermore, multivariate Cox regression analysis revealed that high HPIP expression (P=0.027 and P=0.042) as well as the International Federation of Gynaecology and Obstetrics stage (P=0.003 and P=0.009), lymph node metastasis (P=0.031 and P=0.017), and LVSI (P=0.024 and P=0.046) were independent prognostic factors. In addition, we demonstrated that high HPIP expression (P=0.003) and LVSI (P<0.001) were independently related to lymph node metastasis.ConclusionElevated HPIP expression may contribute to the progression and metastasis of CC and may also serve as a new biomarker to predict the prognosis of CC.
Adverse intrauterine environment has been considered a predisposing factor for fetal programming in preeclampsia. Using human umbilical vein endothelial cells (HUVECs), we specifically explored if aberrant histone methylation occurs in fetal endothelial cells in preeclampsia. Strikingly, we found that increased di-, and trimethylation of histone H3 lysine 9 (H3K9me2 and H3K9me3) expression were associated with upregulation of methyltransferase G9a and downregulation of endothelial nitric oxide synthase and CuZn-SOD expression in preeclamptic HUVECs. We further demonstrated that hypoxia-induced hypermethylation of H3K9 and reduced CuZn-SOD expression mimicked what were seen in preeclamptic HUVECs and inhibition of G9a could attenuate these hypoxia-induced adverse events. Our study was the first to identify hypermethylation status in fetal endothelial cells in preeclampsia, which provides plausible evidence that increased oxidative stress in the intrauterine environment is likely a mechanism to induce aberrant histone modification in fetal endothelial cells which may have a significant impact on fetal programming in preeclampsia.
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