Suppression of E6 Oncogene Induces Apoptosis in CaSki Cervical Cancer Cells.

OBJECTIVE: The most important casuse of cervical cancer incidence and high mortality rate is infection to the human papillomavirus (HPV). The aim of the present study was to investigate the effect of silencing HPV E6 oncogene on cervical cancer cells using specific siRNAs. MATERIALS AND METHODS: CaSki cervical cancer cells, carrying E6 gene, were cultured and then transfected with E6 targeting siRNAs. The cell viability through suppression of E6 expression was explored using MTT assay. Besides, apoptosis induction was investigated by means of flow cytometry using Annexin / PI staining. The changes in the expression of target genes were examined via  Real-Time PCR. RESULTS: E6 gene silencing caused a significant decrease in the survival rate of CaSki cells through remarkable enhancement of apoptosis induction. Moreover, E6 suppression led to significant upregulation of P53, Bax, Caspase-3, and Caspase-9 mRNA expression while downregulated Bcl-2 expression. Interestingly, it was found that suppression of E6 expression could lead to upregulation of  E5 and E7 expression as a compensatory mechanism for E6 deactivation. CONCLUSION: According to the results of this study, suppression of E6 expression using specific siRNAs could be considered as a therapeutic approach for cervical cancer.

Molecular pathways in the development of HPV-induced cervical cancer.

Recently, human papillomavirus (HPV) has gained considerable attention in cervical cancer research studies. It is one of the most important sexually transmitted diseases that can affect 160 to 289 out of 10000 persons every year. Due to the infectious nature of this virus, HPV can be considered a serious threat. The knowledge of viral structure, especially for viral oncoproteins like E6, E7, and their role in causing cancer is very important. This virus has different paths (PI3K/Akt, Wnt/ß-catenin, ERK/MAPK, and JAK/STAT) that are involved in the transmission of signaling paths through active molecules like MEK (pMEK), ERK (pERK), and Akt (pAkt). It's eventually through these paths that cancer is developed. Precise knowledge of these paths and their signals give us the prognosis to adopt appropriate goals for prevention and control of these series of cancer.

Helicobacter pylori Pathogenicity Factors Related to Gastric Cancer.

Background: Although the causal relationship between Helicobacter pylori infection and the development of gastric cancer is firmly established, the exact nature of the pathogenicity factors of H. pylori that predispose to gastric oncogenesis remains incompletely characterized. We investigated the association between H. pylori virulence genotypes and disease in a well-characterized cohort consisting of 109 H. pylori isolates from gastric biopsies originating from patients. Methods: The prevalence of genotype was assessed by PCR and related to clinical histopathological parameters. Results: The relation of babA2 and babB negative and iceA1 positive genotype as a single genotype and the development of cases to GC was statistically significant (P < 0.001). The cagE, cagA, and iceA1 were found more commonly in patients with GC as compared with the other groups. The relation of the presence of iceA1 and the development of cases to GC was statistically significant (P = 0.008), but babA2 and babB alleles were not detected in these patients. These apparent negative associations were still statically significant (P = 0 and 0.005). Conclusion: Our results show an elevated prevalence of infection with H. pylori strains carrying known virulence genotypes with high genetic diversity. This highlights the importance of identifying gene variants for an early detection of virulent genotypes.

Magnetic nanoparticles: Applications in gene delivery and gene therapy.

Gene therapy is defined as the direct transfer of genetic material to tissues or cells for the treatment of inherited disorders and acquired diseases. For gene delivery, magnetic nanoparticles (MNPs) are typically combined with a delivery platform to encapsulate the gene, and promote cell uptake. Delivery technologies that have been used with MNPs contain polymeric, viral, as well as non-viral platforms. In this review, we focus on targeted gene delivery using MNPs.

Real-time PCR detection of 16S rRNA novel mutations associated with Helicobacter pylori tetracycline resistance in Iran.

BACKGROUND: Tetracycline is an antibiotic widely used for the treatment of Helicobacter pylori infection, but its effectiveness is decreasing due to increasing bacterial resistance. The aim of this study was to investigate the occurrence of 16S rRNA mutations associated with resistance or reduced susceptibility to tetracycline of Helicobacter pylori by real-time PCR (RT-PCR) assays from culture. MATERIALS AND METHODS: Tetracycline susceptibility and minimal inhibition concentration (MIC) was determined by the Epsilometer test (Etest) method. A LightCycler assay developed to detect these mutations was applied to DNA extracted from culture. The 16S rRNA of these isolates was sequenced and resistance-associated mutations were identified. From 104 isolates of H. pylori examined, 11 showed resistance to tetracycline. RESULTS: LightCycler assay was applied to DNA extracted from 11 tetracycline-susceptible and 11 tetracycline resistance H. pylori isolates. In our study the sequencing of the H. pylori wild types in 16 s rRNA gene were AGA 926-928 with MIC (0.016 to 0.5 µg/ml), while the sequencing and MIC for resistant were GGA and AGC, (0.75 to 1.5 µg/ml), respectively. Also we found a novel mutation in 2 strains with 84° as their melting temperatures and exhibition of an A939C mutation. CONCLUSIONS: We conclude that real-time PCR is an excellent method for determination of H. pylori tetracycline resistance related mutations that could be used directly on biopsy specimens.