Combined oncolytic adenovirus carrying MnSOD and mK5 genes both regulated by survivin promoter has synergistic inhibitory effect on gastric cancer

Gastric cancer (GC) is one of the major causes of cancer related mortality. The use of oncolytic virus for cancer gene-virotherapy is a new approach for the treatment of human cancers. In this study, a novel Survivin promoter driven recombinant oncolytic adenovirus carrying mK5 or MnSOD gene was constructed, which was modified after deletion of E1B gene. Human plasminogen Kringle 5 mutant ( mK5 ) and manganese superoxide dismutase ( MnSOD ) are both potential tumor suppressor genes. To construct Ad-Surp- mK5 and Ad-Surp- MnSOD oncolytic adenovirus, we hypothesized that the combination of the two viruses would enhance the therapeutic efficacy of GC as compared to the virus alone. The results of the in vitro experiments revealed that the combination of adenovirus carrying mK5 and MnSOD gene exhibited stronger cytotoxicity to GC cell lines as compared to the virus alone, Additionally, the virus could selectively kill cancer cells and human somatic cells. Cell staining, flow cytometry and western blot analysis showed that the combination of two adenovirus containing therapeutic genes could promote the apoptosis of cancer cells. In vivo experiments further verified that Ad-Surp- mK5 in combination with Ad-Surp- MnSOD exhibited significant inhibitory effect on the growth of GC tumor xenograft as compared to the virus alone, and no significant difference was observed in the body weight of treatment and the normal mice. In conclusion, the combination of our two newly constructed recombinant oncolytic adenovirus containing mK5 or MnSOD therapeutic genes could significantly inhibit gastric cancer growth by inducing apoptosis, suggestive of its potential for GC therapy.

Relationship between Superoxide Dismutase Manganese Gene Polymorphism and Eye Tumors

ABSTRACT Background: Orbital tumor in Indonesia is one of the eye health problems that can cause blindness. The impact caused by orbital tumors on patients is quite large because it can result in blindness and even death due to its metastatic nature. The role that SOD plays in cancer biology is not well understood, most studies showing a more oxidative state, characterized by increased intracellular ROS, particularly superoxide. Objective: To determine the relationship between Manganese Superoxide Dismutase (SOD2) gene polymorphisms and the incidence of orbital tumors in Medan. Methods: This study is an analytic observational study with a cross-sectional data collection method using controls. Comparisons were made between the control group and the observed group to see the relationship between SOD2 polymorphisms and the risk of orbital tumor incidence in Medan. The ophthalmic examination, anterior and posterior segments, and assessment of CT orbit if deemed necessary for the orbital tumor patients. Histopathological examination was done by the Pathologist. Blood samples was taken for polymorphism examination on extracted DNA using the Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) methods. Results: About 30 patients that met the inclusion criterias. Laterality, the left eye is more likely to suffer from tumors when compared to the right eye. This study found as many as 16 patients, while malignant tumors was 14 patients. There was a relationship between the MnSOD gene polymorphism and the incidence of orbital tumors (p <0.001), there was a relationship between the MnSOD gene polymorphism and the incidence of orbital tumors in the female sex (p <0.001) Conclusion: There was a relationship between MnSOD gene polymorphisms and the incidence of orbital tumors (p <0.001)

Association of MnSOD gene polymorphism with susceptibility to Kawasaki disease in Chinese children

Background: Kawasaki disease is a type of acute febrile rash disease that is common in children and is characterised by primary lesions of systemic middle and small vasculitis, which can lead to coronary artery lesions. Manganese superoxide dismutase (MnSOD), one of the most important antioxidases in the human body, plays a key role in maintaining the balance of free radicals in the human body. Two single-nucleotide polymorphisms (SNPS) (rs4880 and rs5746136) in the MnSOD gene were related to oxidative stress disease. The purpose of this study is to explore the possible relationship between MnSOD gene polymorphisms and Kawasaki disease susceptibility. Methods: This study included 100 Kawasaki disease children and 102 healthy children. Two single-nucleotide polymorphisms (rs4880 and rs5746136) were detected by polymerase chain reaction sequence-based typing. Results: There was a significant difference in both the genotype frequency (χ2 = 10.805, p = 0.005) and the allele frequency (χ2 = 7.948, p = 0.005) of rs5746136 between the Kawasaki disease group and the control group. Children with the A allele had a 0.558 times lower risk of Kawasaki disease than those without the A allele (χ2 = 7.948, p = 0.005, odds ratio = 0.558, 95% confidence interval = 0.371–0.838). There was no significant difference in the genotype and gene frequencies of rs5746136 between the Kawasaki disease-coronary artery lesion and Kawasaki disease-without coronary artery lesion groups (p > 0.05), and there was no significant difference in the rs4880 genotype and allele frequencies between the Kawasaki disease and healthy control groups or between the Kawasaki disease-coronary artery lesion and Kawasaki disease-without coronary artery lesions groups (p > 0.05). Conclusion: This study provides evidence supporting an association between MnSOD gene polymorphisms and susceptibility to Kawasaki disease. The genotype AA and the allele A of the MnSOD gene locus rs5746136 were risk factors for Kawasaki disease.

Regulation of mitochondrial manganese superoxide dismutase (MnSOD) gene expression in cereals by copper and manganese excess

Within many different cytotoxic activities of heavy metals in plant cells, one of the most important is connected with reactive oxygen species (ROS) generation. Mechanism of plant cell defense against reactive oxygen species and free radicals has a comprehensive character. The aim of presented paper is characterization of changes in mitochondrial manganese superoxide dismutase (MnSOD) gene transcript level that occurred in bread wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) seedlings during copper and manganese treatment. Our results show down-regulation of MnSOD expression in most cases after the oxidative burst evoked by copper excess. Manganese treatment, on the other hand, caused differential reaction of tested material indicating the substantial impact of cultivar genetic background in molecular response to the same stress-inducing conditions.

Polimorfisme V16A Gen MnSOD pada Penderita Diabetes Melitus Tipe 2 dengan Retinopati

Complications of diabetes mellitus (DM) include diabetic retinopathy (RD) both non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). The development of RD depends on environmental and genetic factors. MnSOD gene (manganese-superoxid dismutase) is one of the candidate risk factors gene for RD. The presence of V16A MnSOD gene polymorphism results in decrease of mitochondrial MnSOD enzymes expression and triggers the oxidative stress. Hyperglycemia in DM increases oxidative stress in tissues, including the retina resulting in metabolic abnormalities in the retina, which play a role in the development of DM complications, namely diabetic retinopathy. In Indonesia, especially the Javanese tribes in Yogyakarta, there has never been any research on MnSOD gene polymorphism in type 2 diabetes patients with and without retinopathy. Subjects were Poly Endocrine patients and Eye Polyclinic patients of Dr. Sardjito’s General Hospital, 121 subjects consisting of 63 type 2 DM patients without retinopathy were group 1 (KI) and 58 type 2 DM patients with retinopathy were group 2 (KII) (20 NPDR subjects and 38 PDR subjects). V16A polymorphism of MnSOD gene from leukocytes DNA was analyzed by PCR-RFLP method. From 121 DM subjects, 70 subjects with VV genotype were found, 50 subjects with VA genotype and 1 subject with AA genotype. From 63 non-RD DM subjects, 22 subjects with VA genotypes and 41 subjects with VV genotype were found, while in DM with retinopathy (non-PDR, n = 20) found 6 subjects with VA genotype and 14 subjects with VV genotype, and in DM with retinopathy (PDR, n = 38) found 1 subject with AA genotype, 22 subjects with VA genotype and 15 subjects with VV genotype. In DM with retinopathy (NPDR and PDR, n = 58), 1 subject was found with AA genotype, 27 subjects with VA genotype and 29 subjects with VV genotype.

Expression of some Genes in Response to Cadmium Stress in Triticum aestivum

Heavy metal toxicity has become a universal threat to all life forms, including plants. The main purpose of this study was to identify the gene expression profiling of MAPK, Thioredoxin, and MnSOD genes in wheat seedlings as affected by cadmium treatment. For this experiment, the quantitative Real-Time PCR on RNA isolated from shoots of wheat exposed to CdCl2 at a concentration of 100 mg/L was used. Results showed that in wheat seedling that exposed to cadmium stress for six days of beginning constant cadmium stress, Thioredoxin gene expression showed a large rise compared with the control sample, MnSOD gene expression increased compared with non-treated wheat seedling at the same times, but unlike the Thioredoxin and MnSOD genes, MAPK gene expression has no significant changes. Of course, it is possible that other times of beginning treatments (instead of six days) cause a change in this gene expression.