Expression variations of DNA damage response genes ATM and ATR in blood cancer patients.

Hematological malignancies (HM) constitute a variety of cancers originating in blood, bone marrow (BM), and lymphatic systems. During the last two decades, the incidence of HM has dramatically increased worldwide. The etiology of HM is still debatable. Genetic instability is a major risk factor for HM. DDR network is a complex signal transduction cellular machinery that detects DNA damage and activates cellular repair factors, thus maintaining genomic integrity. DDR network detects a variety of DNA damage and triggers the activation of cell cycle control, DNA repair, senescence, and apoptosis. Among the DNA repairing pathways, the DNA damage response (DDR) pathway includes DNA damage signaling apparatus such as ATM and ATR genes. ATM tends to detect double-strand breaks (DSBs) while ATR detects single-strand DNA (ssDNA). The study was conducted to observe the expression deregulations of DNA damage response (DDR) pathway genes (ATM, ATR) at mRNA level in 200 blood cancer patients and 200 controls. The real-time PCR was used to analyze the expression of the target genes. The expression results showed statistically significant downregulation of ATM (p < 0.0001) and ATR (p < 0.0001) genes in blood cancer patients vs. controls. Moreover, a significant downregulation of ATM (p < 0.0001) and ATR (p < 0.0001) was obtained in chemotherapy-treated patients vs. healthy controls. The results suggest that dysregulation in ATM and ATR genes may be associated with increased blood cancer risk.

Fyn and Lyn gene polymorphisms impact the risk of thyroid cancer.

Thyroid cancer is the most common malignancy of the endocrine glands, and during last couple of decades, its incidence has risen alarmingly, across the globe. Etiology of thyroid cancer is still debatable. There are a few worth mentioning risk factors which contribute to initiation of abnormalities in thyroid gland leading to cancer. Genetic instability is major risk factors in thyroid carcinogenesis. Among the genetic factors, the Src family of genes (Src, Yes1, Fyn and Lyn) have been implicated in many cancers but there is little data regarding the association of these (Src, Yes1, Fyn and Lyn) genes with thyroid carcinogenesis. Fyn and Lyn genes of Src family found engaged in proliferation, migration, invasion, angiogenesis, and metastasis in different cancers. This study was planned to examine the effect of Fyn and Lyn SNPs on thyroid cancer risk in Pakistani population in 500 patients and 500 controls. Three polymorphisms of Fyn gene (rs6916861, rs2182644 and rs12910) and three polymorphisms of Lyn gene (rs2668011, rs45587541 and rs45489500) were analyzed using Tetra-primer ARMS-PCR followed by DNA sequencing. SNP rs6916861 of Fyn gene mutant genotype (CC) showed statistically significant threefold increased risk of thyroid cancer (P < 0.0001). In case of rs2182644 of Fyn gene, mutant genotype (AA) indicated statistically significant 17-fold increased risk of thyroid cancer (P < 0.0001). Statistically significant threefold increased risk of thyroid cancer was observed in genotype AC (P < 0.0001) of Fyn gene polymorphism rs12910. In SNP rs2668011 of Lyn gene, TT genotype showed statistically significant threefold increased risk of thyroid cancer (P < 0.0001). In case of rs45587541 of Lyn gene, GA genotypes showed statistically significant 11-fold increased risk in thyroid cancer (P < 0.0001). Haplotype analysis revealed that AAATAG*, AGACAG*, AGCCAA*, AGCCAG*, CAATAG*, CGCCAG* and CGCCGA* haplotypes of Fyn and Lyn polymorphisms are associated with increased thyroid cancer risk. These results showed that genotypes and allele distribution of Fyn and Lyn are significantly linked with increased thyroid cancer risk and could be genetic adjuster for said disease.

Role of Chk1 gene in molecular classification and prognosis of gastric cancer using immunohistochemistry and LORD-Q assay.

Purpose: The aim of the current study was to assess the prognostic value of the Chk1 gene in the DNA damage response pathway in gastric cancer (GC). Methods: Expression levels of the Chk1 were measured in 220 GC tumor tissues and adjacent healthy/noncancerous tissues using real-time PCR and immunohistochemical staining. Genomic instability in GC patients was measured using the long-run real-time PCR technique for DNA-damage quantification assay and comet assay. Results: Significantly downregulated expression of Chk1 was observed at the mRNA level (p < 0.0001) and protein level (p < 0.0001). Significantly increased frequency of lesions/10 kb and comets was observed in tumor tissues compared with control tissues. Conclusion: The data suggest that downregulated expression of Chk1 and positive Heliobacter pylori infection status may have prognostic significance in GC.

Synthesis and characterization of ZnO decorated reduced graphene oxide (ZnO-rGO) and evaluation of its photocatalytic activity toward photodegradation of methylene blue.

Photocatalytic treatment is one of the techniques used for the treatment of dyes-contaminated wastewater. It is important to develop an effective visible-light-driven catalyst for the treatment of dyes-contaminated wastewater. This study reports the synthesis of ZnO-reduced graphene oxide catalyst for the degradation of methylene blue. Graphene oxide was prepared by Hammer and Offeman process, while ZnO-rGO (1:1) was prepared by the chemical reduction method. The prepared ZnO-rGO composite was characterized by XRD, TEM, SEM, UV-Vis, DRS, N2 adsorption-desorption, FTIR, and XPS analyses. The photocatalytic activity was evaluated by photodegradation of methylene blue solution under irradiation. It was found that ZnO-rGO is capable of removing the dye from water and achieved the highest dye degradation efficiency of ~99% within 60 min. Furthermore, the ZnO-rGO was recycled in degradation experiments without any loss in its catalytic performance. The reaction kinetics was described in terms of the Langmuir-Hinshelwood mechanism, one of the kinetics mechanisms of surface catalyzed reaction. 36.2 and 13.1 kJ/mol were calculated as the apparent and true activation energy for photodegradation of methylene blue respectively.

Association between single nucleotide polymorphisms of DNA damage response pathway genes and increased risk in breast cancer.

Aim: We aimed to evaluate the role of selected single nucleotide polymorphisms of DNA damage response pathway genes in breast cancer (BC). Materials & methods: In present study, 500 BC patients and 500 controls was used to estimate the frequency of single nucleotide polymorphisms of DNA damage response pathway genes. Tetra-amplification refractory mutation system-PCR technique was used for screening of the six selected polymorphisms. Results: Logistic regression analysis showed that heterozygous mutant genotype of rs1800057 (p < 0.0001) and homozygous mutant genotype of rs1801516 (p < 0.0001) was associated with significant increased risk of BC. In the ATR gene, heterozygous mutant genotype of rs2227931 (p < 0.0001) was associated with significant increased risk of BC. However, significant decreased risk of BC was found associated with heterozygous mutant genotype of rs2227928 (p < 0.0002) and homozygous mutant genotype of rs2229032 (p < 0.0001) in patients compared with controls. Conclusion: The present results showed that alteration in DNA damage response pathway gene (ATM & ATR) results in increased BC risk.

Linkage disequilibrium and haplotype analysis of Src and Yes1 genes in thyroid cancer.

Purpose: This study was planned to examine the effects of Src and Yes1 single nucleotide polymorphism (SNPs) on the risk of thyroid cancer in 499 patients and 500 controls. Materials & methods: Three SNPs of Src gene and three SNPs of Yes1 gene were analyzed using Tetra-primer ARMS-PCR followed by sequencing. Results: rs121913314 of Src gene genotype TT showed 32-fold increased risk of thyroid cancer and rs2305994 of Yes1 genotypes TT and CT showed 2.7-fold and 16-fold increased risk in thyroid cancer (p < 0.0001). Haplotype analysis revealed that CATGCC, CATGCT, CATGTC, CATGTT, TATGCC and TATGTTA haplotypes are associated with thyroid cancer risk. Conclusion: Results showed that genotypes and allele distribution of Src and Yes1 genes are significantly linked with increased risk of thyroid cancer.