The aim of this study is to investigate the plasticity of human epithelial ovarian cancer cell SKOV3ip and formation of vasculogenic mimicry (VM) in vivo. SKOV3ip was transfected with lentiviral vector carrying green fluorescence protein (GFP). Female nude mice were implanted intraperitoneally with GFP-labled SKOV3ip. When the transplanted tumor reached a volume of approximately 1 cm(3), paraffin-embedded, formaldehyde-fixed tissue was prepared and stained with hematoxylin and eosin (H & E). Tumor tissues were also studied by electron microscopy and fluorescence microscopy. The results of H & E staining, electron microscopy, and fluorescence microscopy indicated SKOV3ip formed patterned networks with erythrocytes in them, in the absence of vascular epithelial cells, which was a sign that SKOV3ip engaged in VM in vivo. Expression of vascular epithelium marker CD31 was investigated by immunohistochemical staining, immunofluorescence assay, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and flow cytometric analysis (FACS). Factor VIII and vascular endothelial growth factor (VEGF) were also analyzed by FACS. Weak and focal CD31 immunohistochemical staining was found along the channels of tumor cells. Immunofluorescence assay and RT-PCR demonstrated that CD31 was expressed in primary-cultured SKOV3ip. CD31 and Factor VIII, but not VEGF were detected in primary-cultured SKOV3ip by FACS. The present study has shown that human ovarian cancer cell line SKOV3ip may be able to express some specific markers of vascular epithelial cells and has plasticity to form VM in vivo. In the following study, we indicated that hypoxia-inducible factor (HIF)-1alpha inhibitor, rapamycin, could possibly prevent VM and phenotype transformation of SKOV3ip, reflected by down-regulating expression of CD31 and Factor VIII. HIF-1alpha protein expression correlated with CD31 and Factor VIII protein expression in SKOV3ip. These results indicated that VM might be associated with HIF-1alpha.
Background Wilms tumor 1 associated protein (WTAP) modulates other genes via transcriptional and post-transcriptional regulation, in particular, by acting as a N6-methyladenosine writer or binding to the 3’UTR of mRNA, and promotes a variety of tumuors. However, the roles and mechanisms of WTAP in ovarian cancer are unknown. Results In this study, using univariate Cox analysis and online CPTA analysis, we found that WTAP was a poor prognostic factor for ovarian cancer, and its protein expression level was higher in ovarian cancer than in normal tissue. Functionally, WTAP promoted the proliferation, invasion, and migration capability of ovarian cancer, according to the results of real time cellular analysis (RTCA), EdU cell proliferation assay, transwell assay. Subsequently, we identified a module containing 133 genes that were carefully related to WTAP expression through weighted gene co-expression network analysis (WGCNA). By calculating the hazard ratios of these genes and comparing their differences in the WTAP high-expression group and the low-expression group, we observed that there was a significant positive correlation between WTAP and two poor survival-related genes, family with sequence similarity 76 member A (FAM76A) and HBS1 like translational GTPase (HBS1L), which was also verified by quantitative real-time PCR in SKOV3 and A2780 cells. Conclusion WTAP functions as an oncogenic factor that promotes the progression of ovarian cancer in which WTAP-HBS1L/FAM76A axis may be involved. Our study indicates the potential role of WTAP in prognostic biomarker and therapeutic target for ovarian cancer.
With this study, we intended to construct a personalized drug-screening system for platinum-resistant ovarian cancer patients by consulting a patient's medical history, data derived from gene mutation detection, and drug screening results derived from mini-PDX (patient-derived xenograft) models. We also aimed to evaluate the efficacy and safety of our system. Patients and Methods: We selected 12 patients with platinum-resistant ovarian cancer who were treated at our hospital from January 2018 to December 2019 to design a single-arm clinical trial. The subsequent chemotherapeutic plans were selected according to a personalized drug-screening system that circulating tumor DNA (ctDNA) testing and the establishment of mini-PDX models. We then analyzed the patients for clinical benefits side-effects in response to chemotherapy in order to evaluate the clinical effects and safety of our new personalized drug-selection system. Results: We successfully established an individualized and sensitive drug-screening system for the 12 patients. Mini-PDX models verified that potentially effective drugs were identified for 11 of the patients. Treatment resulted in complete remission (one patient), partial remission (five patients), and stable disease (three patients). The remaining three patients experienced disease progression. The overall clinical-benefit rate was 75.0%. Following treatment, the levels of CA125 levels decreased significantly in seven of the 12 patients. Severe side effects, arising from chemotherapy, were only observed in one case. Conclusion:Constructing a personalized drug-screening system for platinum-resistant ovarian cancer patients can be used to guide clinical drug selection and improve the clinical-benefit rate for patients. Trial Registration Number: ChiCTR1800016766 (Chinese Clinical Trial Registry Center).
Objective Postincision pain often occurs after surgery and is an emergency to be treated in clinic. Electroacupuncture (EA) is a Chinese traditional treatment widely used to cure acute or chronic pain, but its mechanism is not clear. Interleukin-10 (IL-10) is a powerful anti-inflammatory cytokine that shows neuroprotective effects in inflammation and injury in the CNS. The present study attempts to reveal that IL-10 is crucial for EA analgesia on postincision pain. Methods A model of incision pain was established in C57BL/6J mice. The pain threshold was detected by behavioral test, and the expression of IL-10 and its receptor was detected by an immunohistochemical method. C-fiber-evoked field potentials were recorded by in vivo analysis. Results The mechanical allodynia induced by paw incision was significantly inhibited by pretreatment of EA in mice. Intrathecal injection of IL-10 neutralizing antibody (2 µg/10 µL) but not intraplantar injection (10 µg/10 µL) reversed the analgesia of EA. The upregulations of IL-10 mRNA and protein were induced by EA at 6 h and 1 d after incision, respectively. Spinal long-term potentiation (LTP), a substrate for central sensitization, was also suppressed by EA with IL-10. IL-10 recombinant protein (1 µg/10 µL, i.t.) mimicked the analgesia of EA on mechanical allodynia and inhibition on the spinal LTP. Posttreatment of EA after incision also transitorily relieved the mechanical allodynia, which can be blocked by spinal IL-10 antibody. IL-10 and its receptor, IL-10RA, are predominantly expressed in the superficial spinal astrocytes. Conclusions These results suggested that pretreatment of EA effectively prevented postincision pain and IL-10 in spinal astrocytes was critical for the analgesia of EA and central sensitization.
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