George Mathew

Bio: George Mathew is an academic researcher from University of Pelita Harapan. The author has contributed to research in topics: Population & Cancer. The author has an hindex of 5, co-authored 12 publications receiving 55 citations.

Proinflammatory response induced by Newcastle disease virus in tumor and normal cells.

Abstract: PURPOSE To investigate the specific role of immune responses induced by lentogenic Newcastle disease virus (NDV) for its antitumor effect. MATERIALS AND METHODS NDV LaSota strain was used to infect the following human cells: non-small cell lung carcinoma (A549), glioblastoma (U87MG and T98G), mammary gland adenocarcinoma (MCF7 and MDA-MB-453), hepatocellular carcinoma (Huh7), transformed embryonic kidney cells (HEK293), primary monocytes, lung fibroblast (HF19), skin fibroblast (NB1RGB) and rat astroglia (RCR-1) at 0.001 multiplicity of infection. NDV-induced cytotoxicity and expression of proinflammatory cytokines were analyzed using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay and multiplex enzyme-linked immunosorbent assay, respectively. RESULTS Tumor cells (A549, U87MG, T98G, Huh7, MDA-MB-453, and MCF7) showed viability of <44%, while normal cell lines HEK293, NB1RGB, and RCR-1 showed 84%, 73%, and 69% viability at 72 hours postinfection, respectively. Proinflammatory cytokine profiling showed that NDV mainly induced the secretion of interferon (IFN)-α, IFN-β, and IFN-λ in tumor cells and only IFN-λ in normal cells. In addition, NDV infection induced the production of interleukin (IL)-6 in most cells. CONCLUSION Our findings suggest a new perspective regarding the role of IFN-λ and IL-6 in the mechanism of tumor selectivity and oncolysis of NDV.

Genetic Risk Factors for Colorectal Cancer in Multiethnic Indonesians

Abstract: Purpose Colorectal cancer is a common cancer in Indonesia, yet it has been understudied. We conduct a genome-wide association study focused on evaluation and discovery of colorectal cancer risk factors in Indonesians. Methods We administered detailed questionnaires and collecting blood samples from 162 colorectal cancer cases throughout Makassar, Indonesia. We also established a control set of 193 healthy individuals frequency matched by age, sex, and ethnicity. A genome-wide association analysis was performed on 84 cases and 89 controls passing quality control. We evaluated known colorectal cancer genetic variants using logistic regression and established a genome-wide polygenic risk model using a Bayesian variable selection technique. Results We replicate associations for rs9497673, rs6936461 and rs7758229 on chromosome 6; rs11255841 on chromosome 10; and rs4779584, rs11632715, and rs73376930 on chromosome 15. Polygenic modeling identified 10 SNP associated with colorectal cancer risk. Conclusions This work helps characterize the relationship between variants in the SCL22A3, SCG5, GREM1, and STXBP5-AS1 genes and colorectal cancer in a diverse Indonesian population. With further biobanking and international research collaborations, variants specific to colorectal cancer risk in Indonesians will be identified.

Antiviral interferons induced by Newcastle disease virus (NDV) drive a tumor-selective apoptosis

Abstract: Newcastle disease virus (NDV) strongly induces both type I and III antiviral interferons (IFNs-α/-β and IFN-λ, respectively) in tumor cells while it induces mainly type III IFN in normal cells. Impairment of antiviral type I IFN signaling in tumor cells is thought to be the reason for effective oncolysis. However, there is lack of clarity why lentogenic strain NDV can also induce oncolysis. NDV infection caused apoptosis in normal and tumor cells as demonstrated with the caspase-3 enzyme activation and annexin-V detection. The apoptosis response was inhibited by B18R protein (a type I IFN inhibitor) in tumor cells i.e. A549 and U87MG, and not in normal cells i.e. NB1RGB and HEK293. Similarly, UV-inactivated medium from NDV infection was shown to induce apoptosis in corresponding cells and the response was inhibited in A549 and U87MG cells with the addition of B18R protein. Treatment with combination of IFNs-α/-β/-λ or IFNs-α/-β or IFN-λ in NB1RGB, HEK293, A549 and U87MG showed that caspase activity in IFNs-α/-β/-λ group was the highest, followed with IFN-α/-β group and IFN-λ group. This suggests that tumor-selectivity of NDV is mainly because of the cumulative effect of type I and III in tumor cells that lead to higher apoptotic effect.

Genetic risk factors for colorectal cancer in multiethnic Indonesians.

Abstract: Colorectal cancer is a common cancer in Indonesia, yet it has been understudied in this resource-constrained setting. We conducted a genome-wide association study focused on evaluation and preliminary discovery of colorectal cancer risk factors in Indonesians. We administered detailed questionnaires and collecting blood samples from 162 colorectal cancer cases throughout Makassar, Indonesia. We also established a control set of 193 healthy individuals frequency matched by age, sex, and ethnicity. A genome-wide association analysis was performed on 84 cases and 89 controls passing quality control. We evaluated known colorectal cancer genetic variants using logistic regression and established a genome-wide polygenic risk model using a Bayesian variable selection technique. We replicate associations for rs9497673, rs6936461 and rs7758229 on chromosome 6; rs11255841 on chromosome 10; and rs4779584, rs11632715, and rs73376930 on chromosome 15. Polygenic modeling identified 10 SNP associated with colorectal cancer risk. This work helps characterize the relationship between variants in the SCL22A3, SCG5, GREM1, and STXBP5-AS1 genes and colorectal cancer in a diverse Indonesian population. With further biobanking and international research collaborations, variants specific to colorectal cancer risk in Indonesians will be identified.

Hepatitis B virus genotypes: Global distribution and clinical importance

Abstract: At least 600000 individuals worldwide annually die of hepatitis B virus (HBV)-related diseases, such as chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Many viral factors, such as viral load, genotype, and specific viral mutations, are known to affect disease progression. HBV reverse transcriptase does not have a proofreading function, therefore, many HBV genotypes, sub-genotypes, mutants, and recombinants emerge. Differences between genotypes in response to antiviral treatment have been determined. To date, 10 HBV genotypes, scattered across different geographical regions, have been identified. For example, genotype A has a tendency for chronicity, whereas viral mutations are frequently encountered in genotype C. Both chronicity and mutation frequency are common in genotype D. LC and progression to HCC are more commonly encountered with genotypes C and D than the other genotypes. Pathogenic differences between HBV genotypes explain disease intensity, progression to LC, and HCC. In conclusion, genotype determination in CHB infection is important in estimating disease progression and planning optimal antiviral treatment.

Oncolytic viruses: how "lytic" must they be for therapeutic efficacy?

Abstract: Oncolytic viruses (OVs) preferentially target and kill cancer cells without affecting healthy cells through a multi-modal mechanism of action. While historically the direct killing activity of OVs was considered the primary mode of action, initiation or augmentation of a host antitumor immune response is now considered an essential aspect of oncolytic virotherapy. To improve oncolytic virotherapy, many studies focus on increasing virus replication and spread. In this article, we open for discussion the traditional dogma that correlates replication with the efficacy of OVs, pointing out several examples that oppose this principle.

The current and future organisational structure of the OIE (World Organisation for Animal Health)

Abstract: Les auteurs se penchent sur la structure organisationnelle de l'OIE (Organisation mondiale de la sante animale) et soulignent le role joue par le Bureau central, les Commissions specialisees, les Commissions regionales, les Groupes de travail et les Groupes ad hoc, les Representations regionales, les Laboratoires de reference et les Centres collaborateurs. Ils livrent egalement quelques pistes de reflexion sur les moyens a mettre en oeuvre par l'OIE pour se rapprocher de ses clients (les Pays Membres), dans l'esprit des dernieres theories en matiere de flexibilite organisationnelle, tout en prenant en compte la situation actuelle de l'OIE et notamment les orientations du Plan strategique et du Plan de travail adoptees en 2001, lors de la 69 e Session generale du Comite international de l'organisation.