Role of sonic hedgehog ligand in gastric cancer therapeutics.

Purpose: The abnormal activation of the sonic hedgehog (SHH) signaling pathway is responsible for the progression of several types of cancers including Gastric Cancer (GC). SHH has been associated with the activation of different signaling pathways. Therefore, in this study, we investigated messenger RNA (mRNA) and protein expression of SHH in gastric malignancies and possible correlation with various clinicopathological parameters. Materials and Methods: A total of 53 surgically resected tumors and adjacent histologically normal tissues from GC patients were investigated in study subjects. A quantitative real-time polymerase chain reaction and immunohistochemistry methods were used for expression analysis of SHH. Results: At mRNA level, SHH was overexpressed in 60% (27/45) of GC cases as compared to their adjacent normal tissues. SHH immunohistochemical analysis revealed abundant cytoplasmic localization and overexpression in 43.39% (23/53) of GC tissues. SHH overexpression was not associated with any of the clinicopathological parameters. Conclusion: Our results showed that SHH is dysregulated in GC and might be considered as a biomarker for GC progression and can be used as a target in cancer therapeutics.

Connective tissue growth factor expression hints at aggressive nature of colorectal cancer.

BACKGROUND: Connective tissue growth factor (CTGF) is a mediator of transforming growth factor-beta signaling and plays a key role in connective tissue remodeling, inflammatory processes and fibrosis in various illnesses including cancer. AIM: To investigate the role of CTGF in colorectal cancer (CRC) progression and to compare the CTGF expression with different clinicopathological parameters. METHODS: Real-time polymerase chain reaction, immunohistochemistry and Western blotting was performed to evaluate the CTGF expression and the results were statistically analyzed against the clinicopathological variables of patient data using STATA software version 16. RESULTS: CTGF expression levels in tumor specimens were significantly higher than their paired normal specimens. The higher protein expression levels showed a significant association with smoking, staging, tumor grade, invasion depth, necrosis of tumor tissue, and both lymphovascular and perineural invasion. As per the cox regression model and classification tree analysis, tumor-node-metastasis stage and perineural invasion were important predictors for CTGF expression and prognosis of CRC patients. Survival analysis indicated that CTGF overexpression was associated with poorer overall and disease-free survival. CONCLUSION: Expression of CTGF was increased in CRC and was linked with poor overall and disease-free survival of CRC patients. These findings support prior observations and thus CTGF may be a possible prognostic marker in CRC.

Effects of Arterial Stiffness on Visual Field Severity and Progression in Malay Patients with Primary Open Angle Glaucoma

@#Introduction: Vascular dysregulation is postulated to be involved in the pathogenesis of primary open angle glaucoma (POAG). Systemic arterial stiffness may accelerate the pre-existing damage. The purpose of this study was to determine the association of arterial stiffness with severity and progression of visual field in Malay patients with POAG. Methods: A cross-sectional study was conducted with 55 patients with POAG and 55 age- and sex-matched control subjects. The patients with POAG were further divided in accordance with their Advanced Glaucoma Intervention Study (AGIS) scores on their visual fields (VFs) (mild in 23 patients, moderate in 18, and severe in 14). Progression was defined as the worsening of the VF defect quantified as an increase in AGIS score of 4 points from the baseline. Arterial stiffness was measured using SphygmoCor and quantified as pulse wave analysis (PWA) and pulse wave velocity (PWV). Results: No significant differences in PWA and PWV were found between the patients with POAG and the control subjects (p=0.333 and p=0.443, respectively). The mean follow-up duration for the patients with POAG was 4.7±3.1 years. PWA and PWV showed no significant association with POAG severity after the confounding factors were controlled for. Ten patients with progression of VF were identified. In the analysis of covariance, a significantly higher PWV was found in the patients with disease progression (p=0.036). Conclusion: VF severity and progression were not associated with systemic arterial stiffness. The probable reason is that other factors affecting retinal microcirculation may play a larger role in the severity and progression of POAG.

Splice site and Germline variations of the MGMT gene in Esophageal cancer from Kashmir Valley: India.

OBJECTIVES: The aim of our investigation was to detect mutation or genetic polymorphisms in MGMT gene of esophageal cancer patients from Kashmir Valley (India). METHODOLOGY: The genetic polymorphisms or mutations in the coding exons 2, 3, 4 and 5 of MGMT gene were searched for in DNA samples from the frozen tumor tissues of 30 esophageal cancer patients from Kashmir. The PCR products were sequenced with fluorescently labelled terminators and separated on automatic sequencer. We developed a new PCR based RFLP approach for genotyping c.459A>G (p.Gly153Gly) variation in 71 esophageal cancer patients and 60 healthy controls. RESULTS: Two somatic variations c.274 +4G>A and c.274 + 22G>A were identified in Exon3-intron 4 boundary. A novel germline variation c.459A>G (p.Gly153Gly) was found in the exon 5 of an esophageal cancer patient. This germline variation was not found in any of the studied esophageal cancer patients and healthy controls except the patient where it has been found by direct sequencing. CONCLUSION: We identified novel sequence variants of the MGMT gene in esophageal cancer patients from Kashmir valley-India.

Lack of influence of MGMT codon Leu84Phe and codon Ileu143Val polymorphisms on esophageal cancer risk in the Kashmir Valley.

The enzyme encoded by the MGMT gene is involved in the repair of alkylated lesions formed in DNA by carcinogenic nitrosamines. Since dietary items consumed by the Kashmiri population contain high concentrations of these agents, it is biologically plausible that MGMT polymorphic variants may be associated with their risk of esophageal cancer. The present study was performed to assess whether non-synonymous SNPS at codon Leu84Phe and codon Ileu143Val of the MGMT gene, close to the active site of the protein, might be linked to predisposition of Kashmiris to esophageal cancer. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism on 92 cases and 77 healthy controls. Codon 84 and codon 143 SNPs of the MGMT gene were not associated with any increase in risk. While the frequency of the Phe allele at codon 84 in cases was (0.16), slightly higher than controls (0.12), the difference was not statistically significant. Similarly, the frequency of Valine allele in cases at codon 143 (0.08) and controls (0.09) was nearly equal. Moreover, no significant association of MGMT genotypes with the clinicopatholgic variables of esophageal cancer patients was observed. In conclusion, MGMT variants at codon 84 and codon143 may not be involved in the susceptibility of the Kashmiri population to esophageal cancer.