Low-Dose Aspirin Has Antiproliferative and Apoptosis Effects in HPV16 Tumor Cells and Delays Tumor Development and Growth in an Experimental Model.

OBJECTIVES: The purpose of this study was to investigate the effect of aspirin on epithelial HPV16-transformed cells and its antitumor effects, in an experimental HPV16-positive tumor model. DESIGN: The design of the study is experimental (in vitro and in vivo). PARTICIPANTS/MATERIALS, SETTING, AND METHODS: SiHa and BMK-16/myc cells were treated with aspirin and cell proliferation was determined by MTT; Caspase-Glo 3/7 Assay was used to determine apoptosis. The tumor-bearing mice group was treated with 50 mg/gr/day of aspirin (orally) during 30 days and the antitumor effect was determined. RESULTS: Here, we provide evidence that aspirin has a negative effect on proliferation and induces apoptosis in the human (SiHa) and murine (BMK-16/myc) HPV16 cells. Furthermore, aspirin showed inhibition of tumor growth, and in mice treated with aspirin prior to implantation of tumor cells, the tumor growth was delayed. Also, the effect of aspirin increased survival in tumor-bearing mice and in mice pre-treated with aspirin. LIMITATIONS: It is necessary to carry out in vitro and in vivo studies of the molecular mechanisms involved in the effects of aspirin on tumor cells. CONCLUSION: Aspirin showed antiproliferative effects in tumor cells and inhibited tumor progression and could be effective as a chemopreventive agent. Thus, aspirin deserves further exploration for the treatment of cervical cancer and other neoplasms.

A1BG and C3 are overexpressed in patients with cervical intraepithelial neoplasia III.

The present study aimed to analyze sera proteins in females with cervical intraepithelial neoplasia, grade III (CIN III) and in healthy control females, in order to identify a potential biomarker which detects lesions that have a greater probability of cervical transformation. The present study investigated five sera samples from females who were Human Papilloma Virus (HPV) 16+ and who had been histopathologically diagnosed with CIN III, as well as five sera samples from healthy control females who were HPV-negative. Protein separation was performed using two-dimensional (2D) gel electrophoresis and the proteins were stained with Colloidal Coommassie Blue. Quantitative analysis was performed using ImageMaster 2D Platinum 6.0 software. Peptide sequence identification was performed using a nano-LC ESIMS/MS system. The proteins with the highest Mascot score were validated using western blot analysis in an additional 55 sera samples from the control and CIN III groups. The eight highest score spots that were found to be overexpressed in the CIN III sera group were identified as α-1-B glycoprotein (A1BG), complement component 3 (C3), a pro-apolipoprotein, two apolipoproteins and three haptoglobins. Only A1BG and C3 were validated using western blot analysis, and the bands were compared between the two groups using densitometry analysis. The relative density of the bands of A1BG and C3 was found to be greater in all of the serum samples from the females with CIN III, compared with those of the individuals in the control group. In summary, the present study identified two proteins whose expression was elevated in females with CIN III, suggesting that they could be used as biomarkers for CIN III. However, further investigations are required in order to assess the expression of A1BG and C3 in different pre-malignant lesions.

Danazol improves thrombocytopenia in HCV patients treated with peginterferon and ribavirin.

BACKGROUND: Thrombocytopenia is a common hematologic disorder observed in patients with chronic hepatitis C virus (HCV) infection. Combined peginterferon (PEG-INF) and ribavirin treatment may exacerbate thrombocytopenia in patients with HCV. OBJECTIVE: The aim of this pilot clinical trial was to assess the efficacy, tolerability and safety of Danazol in thrombocytopenia associated with PEG-INF and ribavirin treatment in patients with HCV. MATERIAL AND METHODS: We included patients whose platelets were < 90,000/mm³ and who were undergoing antiviral treatment. Danazol (300-600 mg/day) was administered during and until the end of antiviral therapy [7.6 months (2 to 11 months)]. The monitoring was performed through platelet analysis and liver function tests. A viral load test was done at the beginning and end of treatment. Fortynine patients receiving a combined therapy of PEG-INF, ribavirin and Danazol increased their platelet levels to 121,081/mm³ (46,000-216,000/mm³); 10.6% of patients gained > 100,000 platelets/mm³, and 71% of patients maintained their initial platelet levels. Sustained viral response (SVR) was achieved in 63% of patients. SVR rates were high in patients with genotype non 1 (78.7%) and decreased in patients with genotype 1 (60.1%). The increase in platelet levels was associated to an increase in fibrinogen levels and a decrease in the activity of ALT. By contrast, patients without SVR presented a delayed response to increased platelet levels and showed no significant improvement in liver function when they received Danazol. CONCLUSION: Danazol can be used along with PEG-INF and ribavirin to treat thrombocytopenia in patients with HCV.