Synergistic effects of exosomal crocin or curcumin compounds and HPV L1-E7 polypeptide vaccine construct on tumor eradication in C57BL/6 mouse model.

Cervical cancer is the most common malignant tumor in females worldwide. Human papillomavirus (HPV) infection is associated with the occurrence of cervical cancer. Thus, developing an effective and low-cost vaccine against HPV infection, especially in developing countries is an important issue. In this study, a novel HPV L1-E7 fusion multiepitope construct designed by immunoinformatics tools was expressed in bacterial system. HEK-293T cells-derived exosomes were generated and characterized to use as a carrier for crocin and curcumin compounds. The exosomes loaded with crocin and curcumin compounds as a chemotherapeutic agent (ExoCrocin and ExoCurcumin) were used along with the L1-E7 polypeptide for evaluation of immunological and anti-tumor effects in C57BL/6 mouse model. In vitro studies showed that ExoCrocin and ExoCurcumin were not cytotoxic at a certain dose, and they could enter tumor cells. In vivo studies indicated that combination of the L1-E7 polypeptide with ExoCrocin or ExoCurcumin could produce a significant level of immunity directed toward Th1 response and CTL activity. These regimens showed the protective and therapeutic effects against tumor cells (the percentage of tumor-free mice: ~100%). In addition, both ExoCrocin and ExoCurcumin represented similar immunological and anti-tumor effects. Generally, the use of exosomal crocin or curcumin forms along with the L1-E7 polypeptide could significantly induce T-cell immune responses and eradicate tumor cells.

The Role of ATP-Binding Cassette Transporters in the Chemoresistance of Anaplastic Thyroid Cancer: A Systematic Review.

Anaplastic thyroid cancer (ATC) is an aggressive type of thyroid cancer with a high mortality rate. Cytotoxic drugs are among the treatment modalities usually used for ATC treatment. However, systemic chemotherapies for ATC have not been shown to have remarkable efficacy. ATP-binding cassette (ABC) transporters have been suggested as a possible mechanism in ATC resistance to chemotherapy. This systematic review was aimed to define the possible roles of ABC transporters in ATC resistance to chemotherapy. Numerous databases, including Scopus, Web of Science, PubMed, Cochrane Library, Ovid, ProQuest, and EBSCO, were searched for papers published since 1990, with predefined keywords. The literature searches were updated twice, in 2015 and 2017. All identified articles were reviewed, and 14 papers that met the inclusion criteria were selected. In the eligible studies, the roles of 10 out of 49 ABC transporters were evaluated; among them, three pumps (ABCB1, ABCC1, and ABCG2) were the most studied transporters in ATC samples. ABCC1 and ABCG2 had the highest expression rates in ATC, and ABCB1 ranked second among the inspected transporters. In conclusion, ABC transporters are the major determinants of ATC resistance to chemotherapy. By identifying these transporters, we can tailor the best treatment approach for patients with ATC. Additional studies are needed to define the exact role of each ABC transporter and other mechanisms in ATC drug resistance.

Effect of adiponectin gene polymorphisms on waist circumference in patients with diabetes.

BACKGROUND: Plasma levels of adiponectin which is secreted from adipose tissue are associated with various parameters of metabolic syndrome. This effect seems to be a result of interactions between genetic and environmental factors including central obesity. The present study was carried out to investigate the possibility of relation between single nucleotide polymorphisms of adiponectin gene (+45 T/G and -11391 G/A) and waist circumferences (WC) in patients with type 2 diabetes. METHODS: This cross-sectional study was conducted on n = 238 diabetic patients selected as cases and n = 159 as healthy control who were recruited from Rafsanjan city in south - east of Iran. The possible association of +45 T/G and -11391 G/A adiponectin gene polymorphisms with WC according to age and sex was evaluated. RESULTS: There was no significant difference in distribution of frequencies of +45 T/G and -11391 G/A adiponectin gene polymorphisms in each group. We only found a significant association between -11391 G/A adiponectin gene polymorphism with WC in diabetic group (p = 0.021). This association was remained significant after adjustment in multivariate regression model (p = 0.019, OR: 0.244, 95%CI: 0.075-0.791) and also this effect was independent of sex and age. CONCLUSION: We found higher abdominal obesity in GA or AA carriers of adiponectin - 11391 G/A genotype in type 2 diabetes patients independent of age and sex.