Research progress of Coxsackievirus A21 / 公共卫生与预防医学

Enteroviruses are currently divided into groups A to J, among which groups A to D can infect human body. People infected with enterovirus can present invisible infection, which can lead to different clinical symptoms when the immunity is weakened. Among the diseases caused by enteroviruses, hand-foot-mouth disease, herpetic angina, and encephalitis have attracted much attention. Coxsackie virus A21 (CV-A21) belongs to enterovirus C group, which mainly causes acute respiratory tract infection. According to research reports, CV-A21 infection has been found in many countries and regions, and the infection scope is gradually expanding. In the past two years, it has been found that CV-A21 infection has a significant association with the outbreak of acute respiratory tract infection. This indicates that acute respiratory tract infection caused by CV-A21 infection may have potential public health problems. However, there are few studies on the epidemiology and pathogenic mechanism of this virus, and most of the studies are on the mechanism of its oncolytic action on specific malignant tumors. Therefore, in this paper, the structural characteristics, epidemiological characteristics, infection mechanism and oncolytic effects of CV-A21 are reviewed to provide relevant clues for the understanding and exploration of CV-A21.

Reoviral Oncotropism Against c-Myc Overexpressing HS 68 Cells

Naturally occurring reoviruses are live replication-proficient viruses specifically infecting human cancer cell while sparing normal counterpart. Since the discovery of reoviruses in 1950s, reoviruses have shown various degrees of safety and efficacy in pre-clinical or clinical application for human anti-cancer therapeutics. I have recently shown that cellular tumor suppressor genes, such as p53, ATM (Ataxia telangiectasia mutated), and RB (Retinoblastoma associated), are important in determining reoviral oncotropism. Thus, it is interesting to examine whether the aberrancy of c-Myc expression, whose normal function also plays an important role in the maintenance of genomic integrity, could affect reoviral oncolytic tropism. Hs68 cells are non-tumorigenic normal cells and resistant to reoviral cytopathic effects. Importantly, I found that c-Myc overexpression in human HS68 cells effectively induced reovirus cytophatic effects compared to mock expressed cells as shown by the typical reoviral cytophathology and an increased level of caspase-3 activity. Taken together, overexpression of c-Myc could play an important role in determining reoviral oncolytic tropism.

Terapia génica para el tratamiento del cáncer / Gene therapy for cancer treatment

El cáncer es una enfermedad compleja de etiología desconocida. Factores genéticos y epigenéticos se asocian al incremento en el riesgo de desarrollar esta enfermedad. A pesar del avance en los tratamientos tradicionales contra el cáncer, el pronóstico de los pacientes no ha mejorado significativamente. Estudios en la patogénesis molecular del cáncer han evidenciado la existencia de dianas moleculares con potencial terapéutico que permiten trasladar los conocimientos de la investigación básica a la clínica implementando nuevas terapias para el beneficio del paciente. El conocimiento del genoma viral, su función, replicación y los mecanismos de infección a la célula tumoral han permitido el desarrollo de la terapia génica viral que puede ser la herramienta ideal para el tratamiento del cáncer. Este artículo revisa diferentes metodologias desarrolladas para el diseno de una terapia génica contra el cáncer, abordada desde diferentes contextos biológicos, y su aplicación clínica para el tratamiento del cáncer.

Cancer is a complicated disease of unknown etiology. Genetic and epigenetic factors are associated with an increased risk for developing this disease. Despite the progress in the traditional cancer therapies, the prognosis of patients has not improved significantly. Studies on the molecular pathogenesis of cancer have demonstrated the existence of molecular targets with therapeutic potential. Furthermore, knowledge of the viral genome function and replication, as well as of the mechanisms of tumor cell infection, have made it possible to develop an ideal tool for gene therapy against cancer and thus, enable the transfer of knowledge from basic to clinical research for the benefit of patients. This article reviews different methodologies developed to design a cancer gene therapy and its clinical application for treating cancer, addressed from various biological contexts.

Comparative analysis of targeted oncolysis of five strain bluetongue virus / 中华微生物学和免疫学杂志

Objective To study the death mode and mechanism of HeLa cancer cell induced by five strain bluetongue virus(BTV). Methods Transmission electron microscope(TEM) was introduced to study changes of ultrastructure. Growth and apoptosis of HeLa cell infected with bluetongue virus were detected with MTT assay and flow cytometry. DNA fragmentation and the activity of caspase-3, -8, -9 were determined by colorimetric assay. Results Many HeLa cells which infected with BTV were observed apoptosis and lyse, and in the plasma were found many viral inclubodies and subviral particles without outer layer proteins. BTV could inhibit HeLa cell proliferation moderately and different serotypes of virus had different effect. Various stages of apoptotic cells were found by flow cytometry and the percentage of apoptosis caused by five strain bluetongue virus were not the same. DNA-Ladder was typical. Caspase-3,-8 ,-9 activity were increased by varying degrees. Conclusion BTV could infect in HeLa cell efficiently and induce it to apoptosis in vitro, then different serotypes of virus have different effect.

Imaging of Viral Thymidine Kinase Gene Expression by Replicating Oncolytic Adenovirus and Prediction of Therapeutic Efficacy

PURPOSE: We have used a genetically attenuated adenoviral vector which expresses HSVtk to assess the possible additive role of suicidal gene therapy for enhanced oncolytic effect of the virus. Expression of TK was measured using a radiotracer-based molecular counting and imaging system. MATERIALS AND METHODS: Replication-competent recombinant adenoviral vector (Ad-deltaE1B19/55) was used in this study, whereas replication-incompetent adenovirus (Ad-deltaE1A) was generated as a control. Both Ad-deltaE1B19/55-TK and Ad-deltaE1A-TK comprise the HSVtk gene inserted into the E3 region of the viruses. YCC-2 cells were infected with the viruses and incubated with 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-5-iodouracil (I-131 FIAU) to measure amount of radioactivity. The cytotoxicity of the viruses was determined, and gamma ray imaging of HSVtk gene was performed. MTT assay was also performed after GCV treatment. RESULTS: On gamma counter-analyses, counts/minute (cpm)/microgram of protein showed MOIs dependency with deltaE1B19/55-TK infection. On MTT assay, Ad-deltaE1B19/55-TK led to more efficient cell killing than Ad-deltaE1A-TK. On plate imaging by gamma camera, both Ad-deltaE1B19/55-TK and Ad-deltaE1A-TK infected cells showed increased I-131 FIAU uptake in a MOI dependent pattern, and with GCV treatment, cell viability of deltaE1B19/55-TK infection was remarkably reduced compared to that of Ad-deltaE1A-TK infection. CONCLUSION: Replicating Ad-deltaE1B19/55-TK showed more efficient TK expression even in the presence of higher-cancer cell killing effects compared to non-replicating Ad-deltaE1A-TK. Therefore, GCV treatment still possessed an additive role to oncolytic effect of Ad-deltaE1B19/55-TK. The expression of TK by oncolytic viruses could rapidly be screened using a radiotracer-based counting and imaging technique.

The value of oncolysis virus in treating liver cancer / 介入放射学杂志

The effect of traditional therapy is limited for liver cancer,gene therapy gets more and more recognition in recent years.Oncolysis virus is a kind of conditionally replicating virus,with special reproductivity in cancer cells,and then kills them.Gene agents are usually introduced into tumor tissue by intra-tumor and intra-arterial injection,and the technique of interventional therapy is able to satisfy the demand excellently.So,some breakthrough is expected in treating liver cancer by skillfully combining oncolysis virus and interventional technique