ABSTRACT
Oncolytic virotherapy is an emerging biotherapeutic platform for selectively infecting cancer cells and triggering apoptosis in a number of malignant cells due to robust viral replication. Studies related to the oncolytic activity of human orthopneumovirus (hOPV) are conflicting. AIM: This study was designed to elucidate the possible role of hOPV in the modulation of cell growth and apoptosis in cancer cell lines including human epidermoid carcinoma (HEp-2), lung epithelial cell line (A549), and breast cancer cell line (MCF-7). MATERIALS AND METHODS: The oncolytic activity of hOPV on cancer cells was studied in vitro. The virus titers were determined by tissue culture infectious dose (TCID50/mL) in A549 cell. The cytotoxic effect of the virus on HEp-2, A549, and MCF-7 was determined using MTT and trypan blue dye exclusion test assays. hOPV in the infected cells was detected using real-time reverse transcription polymerase chain reaction (rRT-PCR) and indirect immunofluorescence (IIF) assays. The relative expression of apoptosis-related genes (CASP-3, -8, -9, Bax, Bcl-2, Bcl-XL, TP53, P21) during virus infection was estimated using rRT-PCR assay in comparison with the house-keeping gene (GAPDH). RESULTS: hOPV infection inhibited the growth of HEp-2, A549, and MCF-7 cells in a dose-and time-dependent manner. At a multiplicity of infection (MOI) of 5, hOPV reduced the viability of A549 cells to about 16%, HEp-2 to 22%, and MCF-7 to 28% (p = 0.001), while no significant inhibitory effect was observed when cells were infected at MOI of 1 and 2. hOPV mRNA and antigens were detected in infected HEp-2, A549, and MCF-7 cells by RT-PCR and IIF. Upon hOPV infection, expression of CASP-3, -8, -9, as well as Bax, TP53, and p21 mRNA increased while expression of Bcl-2, Bcl-xL anti-apoptotic genes decreased. In hOPV-infected A549 cells, the fold increase of CASP-8 and CASP-9, Bax, TP53, and P21 expression exceeded significantly compared to that in HEp-2 or MCF-7 cells. CONCLUSIONS: Our results provide evidence that hOPV could be a potential candidate for oncolytic virotherapy.
Subject(s)
Neoplasms , Proto-Oncogene Proteins c-bcl-2 , Apoptosis/genetics , Humans , MCF-7 Cells , Neoplasms/genetics , Neoplasms/therapy , RNA, Messenger , bcl-2-Associated X Protein/metabolism , bcl-2-Associated X Protein/pharmacologyABSTRACT
The study evaluated the efficacy of fasting in Ramadan on the clinical, laboratory and ultrasonographic parameters of chronic liver disease patients. A total of 202 patients were selected from the departments of Tropical medicine and outpatient clinics of Al-Azhar University hospitals, Cairo, Egypt from the 26th of July till the 30th of September 2010. Patients submitted to complete clinical, laboratory, ultrasonographic and endoscopic evaluation pre, during, and post Ramadan. The fasting group was 103 (51%) and the non-fasting group was 99 (49%) patients. The non-fasting group showed significantly a good adherence to therapy (43.4%) compared to (27.2%) the fasting group (p=0.016). Dyspeptic symptoms was higher in the fasting (53.4%) compared to (38.4%) the non-fasting group (p=0.032). G.I. bleeding during Ramadan was higher in the fasting group (17.5%) compared to non-fasting (14.1%), but the bleeding due to o.v. was significantly higher in the non-fasting group (9.1%) compared to (1%) in the fasting group (p=0.004). Chronic hepatitis in the fasting group showed non significant changes pre, during and post-Ramadan regarding liver function. Fasting cirrhotic group patients child class C was developed to (13%) during and (32.6%) after Ramadan compared to (0%) before (p=0.001).
