Thyroid cancer is rapidly increasing in incidence worldwide. Although most thyroid cancer can be cured with surgery, radioactive iodine, and/or chemotherapy, thyroid cancers still recur and may become chemoresistant. Autophagy is a complex self-degradative process that plays a dual role in cancer development and progression. In this study, we found that miR-125b was downregulated in tissue samples of thyroid cancer as well as in thyroid cancer cell lines, and the expression of Foxp3 was upregulated. Further, we demonstrated that miR-125b could directly act on Foxp3 by binding to its 3' UTR and inhibit the expression of Foxp3. A negative relationship between miR-125b and Foxp3 was thus revealed. Overexpression of miR-125b markedly sensitized thyroid cancer cells to cisplatin treatment by inducing autophagy through an Atg7 pathway in vitro and in vivo. Taken together, our findings demonstrate a novel mechanism by which miR-125b has the potential to negatively regulate Foxp3 to promote autophagy and enhance the efficacy of cisplatin in thyroid cancer. miR-125 may be of therapeutic significance in thyroid cancer.
Dendritic cells (DCs) are professional antigen-presenting cells (APCs) in human immune system. DC-based tumor vaccine has met with some success in specific malignancies, inclusive of breast cancer. In this study, we electrofused MDA-MB-231 breast cancer cell line with day-3 DCs derived from peripheral blood monocytes, and explored the biological characteristics of fusion vaccine and its anti-tumor effects in vitro. Day-3 mature DCs were generated from day-2 immature DCs by adding cocktails composed of TNF-α, IL-1β, IL-6 and PEG2. Day-3 mature DCs were identified and electofused with breast cancer cells to generate fusion vaccine. Phenotype of fusion cells were identified by fluorescence microscope and flow cytometer. The fusion vaccine was evaluated for T cell proliferation, secretion of IL-12 and IFN-γ, and induction of tumor-specific CTL response. Despite differences in morphology, day-3 and day-7 DC expressed similar surface markers. The secretion of IL-12 and IFN-γ in fusion vaccine group was much higher than that in the control group. Compared with control group, DC-tumor fusion vaccine could better stimulate the proliferation of allogeneic T lymphocytes and kill more breast cancer cells (MDA-MB-231) in vitro. Day-3 DCs had the same function as the day-7 DCs, but with a shorter culture period. Our findings suggested that day-3 DCs fused with whole apoptotic breast cancer cells could elicit effective specific antitumor T cell responses in vitro and may be developed into a prospective candidate for adoptivet immunotherapy.
Accumulating evidence suggests that breast cancer originates from cancer stem cells (CSCs), which comprise a small percentage of the overall tumor but are highly tumorigenic and pluripotent with unlimited proliferation potential. Furthermore, CSCs are highly resistant to conventional treatment, which may explain certain difficulties in treating cancer with current therapy options. In this study, the third generation oncolytic herpes simplex virus (oHSV) vector G47∆ effectively killed different subtypes of breast cancer cells, with more than 98% of the tumor cells killed by Day 5. Moreover, G47∆ targeted equally non-cancer stem cells (NCSCs) and CSCs which showed resistance to paclitaxel. We demonstrated that G47∆ effectively replicated and spread among CSCs. G47∆ also impaired the self-renewal ability of CSCs, as the viable cells were unable to form secondary tumor spheres. We also showed that G47∆ was able to induce the regression of tumor xenografts in BALB/c nude mice and demonstrated the ability of G47∆ to synergize with paclitaxel by killing both NCSCs and CSCs, suggesting that oHSV may be an effective treatment modality for patients with breast cancer.
Cavernous nerve injury (CNI) is the main cause of erectile dysfunction (ED) following pelvic surgery. Our previous studies have demonstrated that transplantation of different sources of mesenchymal stem cells (MSCs) was able to alleviate ED induced by CNI in rat models. However, little is known about the therapeutic effects of human gingiva-derived MSCs (hGMSCs) in CNI ED rats. Herein, we injected the hGMSCs around the bilateral major pelvic ganglia (MPG) in a rat model of CNI and evaluated their efficacy. The results showed that treatment of hGMSCs could significantly promote the recovery of erectile function, enhance smooth muscle and endothelial content, restore neuronal nitric oxide synthase (nNOS) expression, and attenuate cell apoptosis in penile tissue. Moreover, penile fibrosis was significantly alleviated after hGMSC administration. In addition, potential mechanism exploration indicated that hGMSCs might exert its functions via skewed macrophage polarity from M1 toward M2 anti-inflammatory phenotype. In conclusion, this study found that transplantation of hGMSCs significantly improved CNI-related ED, which might provide new clues to evaluate their pre-clinical application.
Oxidative stress-induced DNA damage is a known causing factor for many types of tumors, but information on the role of oxidants and antioxidants in thyroid tumors is limited. The aim of this study was to determine antioxidant levels in thyroid tumors. In this study, tumor and its matched non-tumor thyroid tissue samples were obtained from 53 patients with thyroid tumors. The levels of manganese superoxide dismutase (MnSOD), thioredoxin reductase 2 (TXNRD2), glutathione (GSH), glutathione peroxidase (Gpx), catalase (CAT), and 27 kd heat-shock protein (hsp27) were determined in both thyroid tissue samples and cultured thyroid cells by immunohistochemical staining and western blot. Hydrogen peroxide (H2 O2 ) was used to generate oxidant stress in the cell culture experiments. We found that the levels of MnSOD, TXNRD2, GSH, Gpx, and Hsp27 were increased in both malignant and benign tumors, while the level of CAT was decreased. To verify the results of the tissue study, we treated cultured thyroid cells with H2 O2 and found the same pattern of antioxidant changes. Hsp27 was also increased after H2 O2 treatment. The expression of hsp27 was upregulated by 8.24-, 6.96-, and 3.09-fold in thyroid cancer, follicular adenoma, multinodular goiter, respectively. Collectively, our study demonstrated that the levels of hsp27 together with MnSOD, TXNRD2, GSH, and Gpx were significantly upregulated by H2 O2 in thyroid tumors. The increase of these antioxidants is observed in both malignant and benign tumors, particularly in the former. The upregulation of antioxidants is likely a protective mechanism of tumor cells to maintain their survival and growth. J. Cell. Biochem. 117: 2473-2481, 2016. © 2016 Wiley Periodicals, Inc.
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