Background/Aims: Monitoring the appearance and progression of tumors are important for improving the survival rate of patients with ovarian cancer. This study aims to examine circulating tumor cells (CTCs) in epithelial ovarian cancer (EOC) patients to evaluate their clinical significance in comparison to the existing biomarker CA125. Methods: Immuomagnetic bead screening, targeting epithelial antigens on ovarian cancer cells, combined with multiplex reverse transcriptase-polymerase chain reaction (Multiplex RT-PCR) was used to detect CTCs in 211 samples of peripheral blood (5 ml) from 109 EOC patients. CTCs and CA125 were measured in serial from 153 blood and 153 serum samples from 51 patients and correlations with treatment were analyzed. Immunohistochemistry was used to detect the expression of tumor-associated proteins in tumor tissues and compared with gene expression in CTCs from patients. Results: CTCs were detected in 90% (98/109) of newly diagnosed patients. In newly diagnosed patients, the number of CTCs was correlated with stage (p=0.034). Patients with stage IA-IB disease had a CTC positive rate of 93% (13/14), much higher than the CA125 positive rate of only 64% (9/14) for the same patients. The numbers of CTCs changed with treatment, and the expression of EpCAM (p=0.003) and HER2 (p=0.035) in CTCs was correlated with resistance to chemotherapy. Expression of EpCAM in CTCs before treatment was also correlated with overall survival (OS) (p=0.041). Conclusion: Detection of CTCs allows early diagnose and expression of EpCAM in CTC positive patients predicts prognosis and should be helpful for monitoring treatment.
Tumor-associated macrophages are regarded as tumor-enhancers as they have key roles in the subversion of adaptive immunity and in inflammatory circuits that promote tumor progression. Here, we show that cancer cells can subvert macrophages yielding cells that have gained pro-tumor functions. When macrophages isolated from mice or humans are co-cultured with dead cancer cell line cells, induced to undergo apoptosis to mimic chemotherapy, up-regulation of pro-tumor gene expression was identified. Phagocytosis of apoptotic cancer cells by macrophages resulted in their transformation into tumor stem (initiating)-like cells, as indicated by the expression of epithelial markers (e.g., cytokeratin) and stem cell markers (e.g., Oct4) and their capability to differentiate in vitro and self-renew in serum-free media. Moreover, we identified a subset of monocytes/macrophages cells in the blood of cancer (breast, ovarian and colorectal) patients undergoing chemotherapy that harbor tumor transcripts. Our findings uncover a new role for macrophages in tumor development, where they can be transformed into tumor-like cells, potentially by horizontal gene transfer of tumor-derived genes, thus, by taking advantage of chemotherapy, these transformed macrophages promote tumor metastasis by escaping immune surveillance.
Diabetic cardiomyopathy (DCM) remains the major cause of death associated with diabetes. Researchers have demonstrated the importance of impaired cardiac insulin signaling in this process. Insulin resistance (IR) is an important predictor of DCM. Previous studies examining the dynamic changes in autophagy during IR have yielded inconsistent results. This study aimed to investigate the dynamic changes in autophagy and apoptosis in the rat H9c2 cardiomyocyte IR model. H9c2 cells were treated with 500 μM palmitic acid (PA) for 24 hours, resulting in the induction of IR. To examine autophagy, monodansylcadaverine staining, GFP-LC3 puncta confocal observation, and Western blot analysis of LC3I-to-LC3II conversion were used. Results of these studies showed that autophagic acid vesicles increased in numbers during the first 24 hours and then decreased by 36 hours after PA treatment. Western blot analysis showed that treatment of H9c2 cells with 500 μM PA for 24 hours decreased the expression of Atg12-Atg5, Atg16L1, Atg3, and PI3Kp85. Annexin V/PI flow cytometry revealed that PA exposure for 24 hours increased the rate of apoptosis. Together, this study demonstrates that PA induces IR in H9c2 cells and that this process is accompanied by excessive activation of autophagy and increases in apoptosis.
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