Inmunoterapia y Cáncer

Efficacy of DNA vaccines forming e7 recombinant retroviral virus-like particles for the treatment of human papillomavirus-induced cancers.

Lescaille G¹, Pitoiset F, Macedo R, Baillou C, Huret C, Klatzmann D, Tartour E, Lemoine FM, Bellier B.

¹Research Unit UMR CNRS 7211/INSERM 959, 75013 Paris, France.

 

Abstract

Human papillomavirus (HPV) is involved in the development of anogenital tumors and also in the development of oropharyngeal head and neck carcinomas, where HPV-16, expressing the E6 and E7 oncoproteins, is the most frequent serotype. Although vaccines encoding L1 and L2 capsid HPV proteins are efficient for the prevention of HPV infection, they are inadequate for treating established tumors. Hence, development of innovative vaccine therapies targeting E6/E7 is important for controlling HPV-induced cancers. We have engineered a nononcogenic mutated E7-specific plasmo-retroVLP vaccine (pVLP-E7), consisting of plasmid DNA, that is able to form recombinant retrovirus-based virus-like particles (VLPs) that display E7 antigen into murine leukemia virus Gag proteins pseudotyped with vesicular stomatitis virus envelope glycoprotein (VSV-G). pVLP-E7 vaccinations were studied for their ability to generate specific immune responses and for induction of protective immunity against tumor cell challenge in preventive and therapeutic models. The produced VLPs induce the maturation of human dendritic cells in vitro and mount specific E7 T cell responses. Intradermic vaccinations of mice with pVLP-E7 show their efficacy to generate antigen-specific T cell responses, to prevent and protect animals from early TC-1 tumor development compared with standard DNA or VLP immunizations. The vaccine efficacy was also evaluated for advanced tumors in mice vaccinated at various time after the injection of TC-1 cells. Data show that pVLP-E7 vaccination can cure mice with already established tumors only when combined with Toll-like receptor-7 (TLR7) and TLR9 agonists. Our findings provide evidence that pVLPs, combining the advantages of DNA and VLP vaccines, appear to be a promising strategy for the treatment of HPV-induced cancers.

Hum Gene Ther. 2013 May;24(5):533-44. doi: 10.1089/hum.2012.037. Epub 2013 May 6.

http://online.liebertpub.com/doi/abs/10.1089/hum.2012.037 

Md. PhD. Rodney Macedo. Past-president del GII.

Dieta y Sindrome Premenstrual

Intake of selected minerals and risk of premenstrual syndrome.

Chocano-Bedoya PO¹, Manson JE, Hankinson SE, Johnson SR, Chasan-Taber L, Ronnenberg AG, Bigelow C, Bertone-Johnson ER.

¹Department of Public Health, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA.

 

Abstract

Iron, potassium, zinc, and other minerals might impact the development of premenstrual syndrome (PMS) through multiple mechanisms, but few studies have evaluated these relations. We conducted a case-control study nested within the prospective Nurses' Health Study II (1991-2001). Participants were free from PMS at baseline. After 10 years, 1,057 women were confirmed as PMS cases and 1,968 as controls. Mineral intake was assessed using food frequency questionnaires completed in 1991, 1995, and 1999. After adjustment for calcium intake and other factors, women in the highest quintile of nonheme iron intake had a relative risk of PMS of 0.64 (95% confidence interval (CI): 0.44, 0.92; P for trend = 0.04) compared with women in the lowest quintile. Women in the highest quintile of potassium intake had a relative risk of 1.46 (95% CI: 0.99, 2.15; P for trend = 0.04) compared with women in the lowest quintile. High intake of zinc from supplements was marginally associated with PMS (for intake of ≥25 mg/day vs. none, relative risk = 0.69, 95% CI: 0.46, 1.02; P for trend = 0.05). Intakes of sodium, magnesium, and manganese were unrelated to PMS risk. These findings suggest that dietary minerals may be useful in preventing PMS. Additional studies are needed to confirm these relations.

KEYWORDS:

dietary iron; minerals; premenstrual syndrome

Am J Epidemiol. 2013 May 15;177(10):1118-27. doi: 10.1093/aje/kws363. Epub 2013 Feb 26.

http://aje.oxfordjournals.org/content/177/10/1118.long

Md. PhD. Patricia Chocano. Ex miembro del GII.