To be effective, therapeutic cancer vaccines should stimulate both an effective cell-mediated and a robust cytotoxic CD8+ T-cell response against human papillomavirus (HPV)-infected cells to treat the pre-existing tumors and prevent potential future tumors. In this study, the therapeutic experiments were designed in order to evaluate antitumor effect against the syngeneic TC-1 tumor model. The anti-tumor efficacy of a HPV-16 E7 DNA vaccine adjuvanted with melatonin (MLT) was evaluated in a C57BL/6 mouse tumor model by measuring tumor growth post vaccination and the survival rate of tumor-bearing mice, analyzing the specific lymphocyte proliferation responses in control and vaccinated mice by MTT assay. The E7-specific cytotoxic T cells (CTL) were analyzed by lymphocyte proliferation and lactate dehydrogenates (LDH) release assays. IFN-γ, IL-4 and TNF-α secretion in splenocyte cultures as well as vascular endothelial growth factor (VEGF) and IL-10 in the tumor microenvironment were assayed by ELISA. Our results demonstrated that subcutaneous administration of C57BL/6 mice with a DNA vaccine adjuvanted with MLT dose-dependently and significantly induced strong HPV16 E7-specific CD8+ cytotoxicity and IFN-γ and TNF-α responses capable of reducing HPV-16 E7-expressing tumor volume. A significantly higher level of E7-specific T-cell proliferation was also found in the adjuvanted vaccine group. Furthermore, tumor growth was significantly inhibited when the DNA vaccine was combined with MLT and the survival time of TC-1 tumor bearing mice was also significantly prolonged. In vivo studies further demonstrated that MLT decreased the accumulation of IL-10 and VEGF in the tumor microenvironment of vaccinated mice. These data indicate that melatonin as an adjuvant augmented the cancer vaccine efficiency against HPV-associated tumors in a dose dependent manner.

BackgroundSince there is no effective treatment or vaccine against the congenital cytomegalovirus (cCMV) infection, knowledge and awareness of medical doctor’s (MDs) especially family doctors are essential for preventive strategies and it also seems to be usually ignored by healthcare providers. Aim of this study was to investigate awareness of MDs about cCMV infection in Iran.MethodsA single page questionnaire was randomly distributed among 450 MDs including general practitioners, pediatricians, gynecologists, internal and other medical specialists concerning of their knowledge in clinical presentation, diagnosis, prevention, prognosis, epidemiology, transmission, and management of cCMV infection. All statistical analyses were performed using SPSS version 16.ResultsMore than half of questionnaire recipients refused to take part in any of the questionnaire items. The most of the respondents were agreed for newborn CMV screening tests and mandatory CMV test for women trying to get pregnant, which, are not routinely tested. The knowledge of general practitioners about cCMV was less than usual. The field of expertise had a profound effect in this survey, but age and gender did not.ConclusionsOur results indicated that the knowledge of cCMV infection, especially among family doctors contains several gaps. Urgent action is required to improve family doctor’s knowledge of CMV infection. Surveys to evaluate CMV awareness among MDs, healthcare professionals and women of childbearing age are proposed.Electronic supplementary materialThe online version of this article (10.1186/s13052-018-0470-4) contains supplementary material, which is available to authorized users.

No abstract