The proliferation, apoptosis, invasion of endothelial-like epithelial ovarian cancer cells induced by hypoxia

<p>Abstract</p> <p>Background</p> <p>Epithelial ovarian cancer is one of the most malignant cancers in women because metastasis occurs in the most of patients by the time of diagnosis. Cancer cells have strong capacity to form angiogenesis or vasculogenic mimicry, which plays the major role in its malignant phenotype. Vasculogenic mimicry might contribute to the failure of the angiogenesis-targeted therapy strategies. Under the microenvironment of the tumor, hypoxia is the most common phenomena because of the vast energy and oxygen consuming. In the present study, the endothelial-like cells induced by hypoxia from SKOV-3 and ES-2 ovarian cancer cells were harvested to investigate the changes in their biological behaviors.</p> <p>Methods</p> <p>The endothelial-like cells from SKOV-3 and ES-2 cells were harvested by laser capture microdissection. The biological behaviors of the endothelial-like cells, including proliferation, cell cycle, apoptosis, invasion and telomerase activity were determined by MTT, FCM, Transwell chamber and TRAP-ELISA methods. HIF-1α is the most important factor for the behavior changes under hypoxic condition. Some other genes relative to biological behaviors are also changes following the changes of HIF-1α. In order to elucidate the underlying mechanisms for these changes by hypoxia, the relative genes expressions including HIF-1α, CyclinD1, Flk-1, VEGF, p53 and V-src were determined by real-time PCR.</p> <p>Results</p> <p>SKOV-3 and ES-2 cells were resistant to hypoxia by adoption of proliferation, apoptosis, differentiation and invasion. Combined with other studies, the more poorly cancer cells differentiate, the more strongly cells are resistant to hypoxia, the more possible to form vasculogenic mimicry. The changes in the expression of HIF-1α, and HIF-1α-dependent VEGF, Flk-1, Cyclin D1, and HIF-1α-independent p53 have been involved in this process.</p> <p>Conclusions</p> <p>HIF-1α took an important role in the behavioral changes of SKOV-3 and ES-2 cells by hypoxia. At the same time, other mechanisms were also involved in this process.</p

Recurrence of ovarian squamous cell carcinoma with MET gene copy number variation: a case report and review of literature

Abstract Background Malignant transformation such as ovarian squamous cell carcinoma (SCC) in ovarian mature cystic teratoma (OMCT) is a rare tumor. The gene mutation of ovarian SCC remains unclear. We herein report a recurrent case of ovarian squamous cell carcinoma with MET gene copy number variation. Case presentation A 60-year-old woman presented with recurrence of ovarian SCC 8 months after primary surgery. Adhesiolysis, right abdominal wall mass excision, prosthetics, enterectomy, enterostomy and partial cystectomy were performed by laparoscope. Pathologic examination demonstrated metastatic squamous cell carcinoma in ileocecus, rectum and abdominal wall muscle. MET gene copy number was elevated with copy number of six in this case. Postoperatively, the patient was treated with four cycles of combination chemotherapy with docetaxel and carboplatin. The patient was free of disease at 20 months’ follow-up. Conclusions Optimal cytoreductive surgery combined with platinum-based chemotherapy is recommended currently for not only primary tumor but also recurrence. For patients with malignant transformation in OMCT, prompt diagnosis and individualized treatment are crucial for better prognosis. Increased copy number of MET may be correlated with her poor PFS and can be a potential therapeutic target for this case

FASDQ: Fault-Tolerant Adaptive Scheduling with Dynamic QoS-Awareness in Edge Containers for Delay-Sensitive Tasks

As the requirement for real-time data analysis increases, edge computing is being implemented to leverage the resources of edge devices to reduce system response times and decrease the latency. However, due to the resource constraints of edge clouds, edge servers are more prone to failures than other systems. Therefore, guaranteeing the reliability of services in edge clouds is critical. In this paper, we propose a fault-tolerant adaptive scheduling mechanism with dynamic quality of service (QoS) awareness (FASDQ), which extends the primary/backup (PB) model by applying QoS on demand to task copies. The aim of the method is to reduce the latency and achieve reliable service for tasks by changing the execution time of task copies. This paper also proposes a container resource-adaptive adjustment mechanism, which adjusts the timing of resources when the available resources cannot meet the task copy requirements. Finally, this paper reports the results of simulation experiments on the EdgeCloudSim platform to evaluate the difference in performance between FASDQ and other methods. The results show that the mechanism effectively reduces the execution time of task copies and outperforms other methods in terms of reliability and general resource utilization

The Expression and Role Analysis of Methylation-Regulated Differentially Expressed Gene UBE2C in Pan-Cancer, Especially for HGSOC

High-grade serous ovarian cancer (HGSOC) is the most fatal gynecological malignant tumor. DNA methylation is associated with the occurrence and development of a variety of tumor types, including HGSOC. However, the signatures regarding DNA methylation changes for HGSOC diagnosis and prognosis are less explored. Here, we screened differentially methylated genes and differentially expressed genes in HGSOC through the GEO database. We identified that UBE2C was hypomethylation and overexpression in ovarian cancer, which was associated with more advanced cancer stages and poor prognoses. Additionally, the pan-cancer analysis showed that UBE2C was overexpressed and hypomethylation in almost all cancer types and was related to poor prognoses for various cancers. Next, we established a risk or prognosis model related to UBE2C methylation sites and screened out the three sites (cg03969725, cg02838589, and cg00242976). Furthermore, we experimentally validated the overexpression of UBE2C in HGSOC clinical samples and ovarian cell lines using quantitative real-time PCR, Western blot, and immunohistochemistry. Importantly, we discovered that ovarian cancer cell lines had lower DNA methylation levels of UBE2C than IOSE-80 cells (normal ovarian epithelial cell line) by bisulfite sequencing PCR. Consistently, treatment with 5-Azacytidine (a methylation inhibitor) was able to restore the expression of UBE2C. Taken together, our study may help us to understand the underlying molecular mechanism of UBE2C in pan-cancer tumorigenesis; it may be a useful biomarker for diagnosis, treatment, and monitoring, not only of ovarian cancer but a variety of cancers

Human mesenchymal stem cells in the tumour microenvironment promote ovarian cancer progression: the role of platelet-activating factor

Abstract Background The tumour microenvironment conferred by mesenchymal stem cells (MSCs) plays a key role in tumour development and progression. We previously determined that platelet-activating factor receptor (PAFR) was overexpressed in ovarian cancer cells (OCCs) and that PAF can promote ovarian cancer progression via PAF/PAFR-mediated inflammatory signalling pathways. Evidence suggests that MSCs can secrete high concentrations of PAF. Here, we investigated the role of PAF/PAFR signalling in the microenvironment mediated by MSCs and OCCs and its effect on cancer progression. Methods The PAF concentrations in the culture media of MSCs, OCCs and co-cultured MSCs and OCCs were determined by ELISA. The effects of MSCs on OCCs in vitro were assessed on cells treated with conditioned medium (CM). The expression and phosphorylation of key proteins in the PAF/PAFR signalling pathway were evaluated. In vivo, MSCs/RFP and SKOV3 cells were co-administered at different proportions to nude mice by interscapular injection. Mice in the WEB2086 group were intraperitoneally injected with the PAFR antagonist WEB2086 at a dose of 1 mg/kg.d for the duration of the animal experiments. Tumour progression was observed, and the weight and survival time of mice were measured. The PAF concentration in peripheral and tumour site blood was determined by ELISA. Results High concentrations of PAF were detected in CM from MSCs and MSCs co-cultured with OCCs. Both types of medium promoted non-mucinous OCC proliferation and migration but had no effect on mucinous-type OCCs. These effects could be blocked by PAFR inhibitors. The expression and phosphorylation of key proteins in the PAF/PAFR pathway significantly increased upon treatment with PAF and MSC-CM. In vivo, the tumour volume was larger following co-injection of SKOV3 cells and MSCs/RFP than following injection of SKOV3 cells alone. The tumour-promoting effect of MSCs/RFP was blocked by the PAFR antagonist WEB2086. Serum PAF concentrations significantly increased in co-injected mice. Conclusion Our results suggest that the tumour-promoting effect of MSCs on OCCs via their cross-talk in the tumour microenvironment was, at least in part, mediated by the PAF/PAFR pathway, suggesting a new target for the treatment of ovarian cancer

Transcriptome analysis of hepatopancreas of Eriocheir sinensis with hepatopancreatic necrosis disease (HPND).

Hepatopancreatic necrosis disease (HPND) is a newly emerging disease in the Chinese mitten crab, Eriocheir sinensis, which has resulted in large economic losses. However, the underlying cause of this disease remains unclear. To better understand the pathogenesis and pathogenic mechanism of HPND, we compared the transcriptome differences of the hepatopancreas of E. sinensis with and without HPND. The analysis yielded > 30 million reads for each sample of three test (with HPND) and three control groups (without HPND). We observed 978 downregulated genes and 644 upregulated genes. Among the gene ontology categories "biological process," "cellular component," and "molecular function", the subcategories cellular process, single-organism process, biological regulation, metabolic process, cell part, organelle, organelle part, binding, and catalytic were enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that "metabolism of xenobiotics by cytochrome P450," "drug metabolism-cytochrome P450," "chemical carcinogenesis," and "material metabolism" were the "five" most significantly enriched pathways in the hepatopancreas of E. sinensis with HPND. The results revealed that material metabolic abnormalities and drug effects from the external environment might be associated with HPND in the Chinese mitten crab. Considering the wide use of pyrethroids for pond cleaning in Xinghua city, we speculated that pyrethroids might cause HPND in the Chinese mitten crab. Our study provided useful information about the cause and pathogenetic mechanisms of HPND and could help to prevent this disease in production practice

DataSheet_1_A durable response to programmed cell death 1 blockade in a multidrug-resistant recurrent ovarian cancer patient with HLA-B44 supertype: A case report.pdf

Relapsed/refractory ovarian cancer, especially platinum resistance recurrence, remains a major therapeutic challenge. Here, we present the case of a patient with recurrent ovarian clear cell carcinoma (OCCC) who failed to respond to multiline chemotherapy and target therapy but achieved an immune complete response (iCR) with programmed cell death 1 (PD-1) inhibitor treatment. The overall survival (OS) was 59 months, and the recurrence-free survival (RFS) was 34 months after immunotherapy, which was counting. Meantime, molecular testing results revealed that traditional biomarkers for immunotherapy, including PD-L1 expression, microsatellite instability (MSI), and tumor mutational burden (TMB), were negative. HLA-B44 (B*18:01) supertype was confirmed by sequence-based HLA typing. This case raises the possibility that ovarian cancer patients with multidrug resistance may still benefit from PD-1 inhibitor therapy, even if PD-L1 pathology is negative.</p