ABSTRACT
We infected HeLa cells with low (10(-9) units), medium (10(-6) units), and high (10(-2) units) influenza B titers and compared the resulting human papilloma virus (HPV), retinoic acid receptor alpha subunit (RARalpha) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA content of surviving infected hosts with that of their uninfected precursors by semi-quantitative reverse transcriptase/polymerase chain reaction amplification (RT/PCR). This comparison revealed a moderate and drastic dependence of HPV and RARalpha mRNA content, respectively, but a complete independence of GAPDH mRNA expression on viral titer. A mechanism of adoptive replacement of tolerable cellular with viral gene expression was proposed to explain these findings. We conclude that the reported ability of influenza B viruses to specifically target and eliminate the cervical adenocarcinoma HeLa cell line studied may find practical applications in biological cancer management.
Subject(s)
Adenocarcinoma/virology , Influenza B virus/pathogenicity , Oncolytic Virotherapy , Oncolytic Viruses/pathogenicity , Uterine Cervical Neoplasms/virology , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/therapy , Antigens, Viral/metabolism , Apoptosis , Cell Survival , Female , Gene Expression Regulation, Neoplastic , Gene Expression Regulation, Viral , Glyceraldehyde-3-Phosphate Dehydrogenases/genetics , Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism , HeLa Cells , Human papillomavirus 18/genetics , Human papillomavirus 18/metabolism , Humans , Influenza B virus/genetics , Influenza B virus/immunology , Oncolytic Viruses/genetics , Oncolytic Viruses/immunology , Phenotype , RNA, Messenger/metabolism , Receptors, Retinoic Acid/genetics , Receptors, Retinoic Acid/metabolism , Retinoic Acid Receptor alpha , Reverse Transcriptase Polymerase Chain Reaction , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/therapyABSTRACT
BACKGROUND: Advanced ovarian cancer is the leading non-breast gynaecologic cause of malignant pleural effusion. Aim of this study was to assess the efficacy of mitoxantrone sclerotherapy as a palliative treatment of malignant pleural effusions due to ovarian cancer. METHODS: Sixty women with known ovarian cancer and malignant recurrent symptomatic pleural effusion were treated with chest tube drainage followed by intrapleural mitoxantrone sclerotherapy. Survival, complications and response to pleurodesis were recorded. The data are expressed as the mean +/- SEM and the median. RESULTS: The mean age of the entire group was 64 +/- 11,24 years. The mean interval between diagnosis of ovarian cancer and presentation of the effusion was 10 +/- 2,1 months. Eighteen patients (30%) had pleural effusion as the first evidence of recurrence. The mean volume of effusion drained was 1050 +/- 105 ml and chest tube was removed within 4 days in 75% of patients. There were no deaths related to the procedure. Side effects of chemical pleurodesis included fever (37-38,5 degrees C) chest pain, nausea and vomiting. At 30 days among 60 treated effusions, there was an 88% overall response rate, including 41 complete responses and 12 partial responses. At 60 days the overall response was 80% (38 complete responses and 10 partial responses). The mean survival of the entire population was 7,5 +/- 1,2 months. CONCLUSIONS: Mitoxantrone is effective in the treatment of malignant pleural effusion secondary to ovarian cancer without causing significant local or systemic toxicity.
