Human papillomavirus (HPV) is the etiologic agent for cervical cancer. In Mexico, a women dies every 2 h, and since 1990 the statistics have shown that the numbers of deaths are increasing. We conducted a phase II clinical trial to evaluate the potential use of the MVA E2 recombinant vaccinia virus in treating high-grade lesions (CIN 2 and CIN 3) associated with oncogenic papillomavirus. Fifty-four female patients with high degree lesions were treated either with an MVA E2 therapeutic vaccine or with conization. Thirty-four women received the therapeutic vaccine, at a total of 10 7 virus particles per dose injected directly into the uterus once every week over a 6-week period. Twenty control patients were treated with conization. By colposcopy, 19 patients out of 34 showed no lesion, in three patients the lesions were reduced by 85-90%, in eight other lesions had reduced by 60%, and in four more patients, they were reduced by 25%. Histological analysis showed total elimination of high-grade lesions in 20 out of 34 patients after treatment with MVA E2. Eleven patients had a 50% reduction in lesion size. In two other patients, the lesion was reduced to CIN 2 and in one more patient the lesion was reduced to low grade (CIN 1). All patients developed antibodies against the MVA E2 vaccine, and generated a specific cytotoxic response against papilloma-transformed cells. DNA viral load was significantly reduced in MVA E2-treated patients. Conization eliminated the lesions in 80% of the patients, but patients did not develop cytotoxic activity specific against cancer cells and did not eliminate the papillomavirus. In addition, three patients treated with conization had recurrence of lesions 1 year later. These results show that therapeutic vaccination with MVA E2 proved to be very effective in stimulating the immune system against papillomavirus, and in generating regression of high-grade lesion.

Our results show: (1) A strong association between rs9939609 SNP of the FTO gene variant and obesity in Spanish morbidly obese adult patients; (2) positive correlations between FTO mRNA and leptin, perilipin, and visfatin gene expressions in subcutaneous adipose tissue; (3) FTO and perilipin gene expressions were positively correlated in visceral fat depot. Overall these results may suggest a role of FTO in the regulation of lipolysis as well as in total body fat rather in fat distribution patterns.

GONZÁ LEZ-SÁ NCHEZ, JOSÉ L., CARINA A. ZABENA, MARÍA T. MARTÍNEZ-LARRAD, CRISTINA FERNÁ NDEZ-PÉ REZ, MILAGROS PÉ REZ-BARBA, MARKKU LAAKSO, AND MANUEL SERRANO-RÍOS. An SNP in the adiponectin gene is associated with decreased serum adiponectin levels and risk for impaired glucose tolerance. Obes Res. 2005;13:807-812. Adiponectin is a plasma protein produced by the adipose tissue. Hypoadiponectinemia has been associated with insulin resistance and several components of the metabolic syndrome (MS): type 2 diabetes, obesity, and dyslipidemia. We investigated whether single nucleotide polymorphisms (SNPs) at positions 45 and 276 in the adiponectin gene were associated with features of the MS in 747 unrelated Spanish subjects. The G allele of SNP45 and the G/G genotype of SNP276 were associated with impaired glucose tolerance (p ϭ 0.020 and 0.042, respectively). The G/G genotype for SNP276 was associated with lower serum adiponectin levels as compared with the G/T and T/T genotypes (G/G, 10.10 Ϯ 0.24 g/mL; G/T, 10.98 Ϯ 0.32 g/mL; T/T, 12.00 Ϯ 0.92 g/mL; p ϭ 0.015) even after adjustment for sex, age, BMI, waist-to-hip ratio, homeostasis model assessment index, and the degree of glucose tolerance (p ϭ 0.040). We found a significant negative association of circulating adiponectin levels with waist-to-hip ratio (r ϭ Ϫ0.42, p Ͻ 0.001), sagittal abdominal diameter (r ϭ Ϫ0.24, p Ͻ 0.001), triglycerides (r ϭ Ϫ0.32, p Ͻ 0.001), homeostasis model assessment index (r ϭ Ϫ0.14, p ϭ 0.001), and uric acid (r ϭ Ϫ0.36, p Ͻ 0.001) and positive association with high-density lipoprotein-cholesterol (r ϭ 0.41, p Ͻ 0.001). Our findings indicate that serum adiponectin levels are associated with several components of the MS. The SNP276 of the adiponectin gene may affect impaired glucose tolerance and hypoadiponectinemia.

No abstract