Study of the Possible Alleviated Role of Atorvastatin on Irinotecan-Induced Lingual Mucosal Damage: Histological and Molecular Study.

BACKGROUND: Oral mucositis is the most debilitating and troublesome adverse effect of irinotecan (CPT-11) treatment. It adversely affects the patient quality of life. The aim of this work was to study the histological, immunohistochemical, and molecular changes in the oral mucosa by CPT-11 and the possible alleviated role of atorvastatin. METHODS: Rats were randomly divided into control, CPT-11-treated group, and CPT-11+ atorvastatin-treated group. At the end of the experiment, the anterior two-thirds of the tongue was dissected out and divided into two parts: one part for light microscopic examination and the second for molecular study. RESULTS: CPT-11-treated group revealed loss of normal mucosal organization, areas of ulceration and inflammation, and loss of architecture of lingual papillae. A significant decrease in immunohistochemical and molecular gene expression of Ki-67 and antiapoptotic Bcl-2 levels was observed. A significant increase in NF-κB immunohistochemical and mRNA gene expression level and a nonsignificant increase in Nrf2 gene expression were detected. Coadministration of atorvastatin showed remarkable improvement in the histopathological picture with a significant increase in Ki-67 and Bcl-2, a significant decrease in NF-κB protein and gene expression, and a significant increase in Nrf2 gene expression. CONCLUSION: Atorvastatin substantially attenuates CPT-11-induced oral mucositis through the initiation of the antiapoptotic gene, modulation of the inflammatory, and antioxidant gene expression.

Significance of BRAFV600E mutation in intra-axial brain tumor in Malaysian patients: case series and literature review.

BACKGROUND: To date, BRAF mutations in brain tumor patients have not been characterized in the Malaysian population. Based on the numerous reported studies, there are main mutations that exist in BRAF gene in various types of cancers. A missense mutation in codon 600 of the BRAF nuclear oncogene (BRAFV600E) is the most prevalent hotspot point mutation that has been identified in multiple human malignancies. AIM: We here aimed to find out the frequency of BRAFV600E mutation in a series of Malaysian patients with brain tumors and if any association exists between BRAFV600E mutation and clinicopathological features of patients. MATERIAL AND METHODS: Fresh frozen tumor tissue samples from 50 Malaysian brain tumor patients were analyzed for BRAFV600E mutational status, and its correlation with clinicopathological features (including age, gender, and tumor localization such as intra-axial: within the brain substance or extra-axial: outside the brain substance) was examined. RESULTS: The overall BRAFV600E mutation frequency was determined to be 22% (in 11 of 50 patients). BRAFV600E was significantly correlated with the tumor location group, which shows BRAFV600E was more frequent in the intra-axial tumor than the extra-axial tumor group. In this study, we also observed that male patients were slightly more susceptible to BRAFV600E mutation, and this mutation was predominant in patients of the age group < 40 years. However, these parameters did not translate to statistical significance. CONCLUSION: The data demonstrate that BRAFV600E mutation is observed significantly more often in intra-axial brain tumor patients, which can serve as baseline information for further research on genetic alteration that occurs during brain tumor progression in the Malaysian population.

Genetic variants of XRCC1 and risk of hepatocellular carcinoma in chronic hepatitis C patients.

BACKGROUND: Hepatitis C virus (HCV) related liver cirrhosis occurs in about 20% of chronically infected patients over a duration of 10-20 years, and within 5 years approximately 10-20% of these cirrhotic patients will develop hepatocellular carcinoma (HCC). Previous studies report that the X-ray repair cross-complementing group1 gene (XRCC1) is important in the risk of HCC development; however, results obtained from these studies are conflicting rather than conclusive. We hypothesised an association between single nucleotide polymorphisms (SNPs) in XRCC1 with the HCC risk on a background of chronic hepatitis C. MATERIALS AND METHODS: We recruited 210 subjects, 70 with HCC, 70 with cirrhosis and 70 healthy controls. Two SNPs [c.1254C>T(rs2293035) and c.1517G>C(rs139599857)] in XRCC1 were genotyped using created restriction site-polymerase chain reaction (CRS-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS: The TT genotype, CT genotype and T-allele in c.1254C>T (rs2293035) were linked to risk of HCC compared to the CC genotype: OR 3.58 [confidence interval (CI) 95%: 1.19-10.7] p = 0.019; OR 2.16 (CI 95%: 1.04-4.47) p = 0.037 and OR 2.10 (CI 95%: 1.2-3.3) p = 0.006, respectively. Regarding c.1517G>C (rs139599857), the CC genotype, GC genotype and C-allele were linked with higher risk of developing HCC compared to GG genotype: OR 4.77 (CI 95%: 1.3-16.9), p = 0.016; OR 3.02 (CI 95%: 1.46-6.2), p = 0.002 and OR 2.4 (CI 95%: 1.4-4.0), p = 0.001, respectively. CONCLUSION: We conclude that the T-allele of c.1254C>T (rs2293035) and the C allele of c.1517G>C (rs139599857) genetic variants may be associated with increased HCC risk among chronic hepatitis C patients.

The epidemiology of multicomponent blood transfusion: a systematic review.

We performed a systematic review to describe the prevalence of multicomponent blood transfusion and, as a secondary objective, to determine patient characteristics and outcomes associated with multicomponent transfusion. There is a lack of literature on the epidemiology of multicomponent transfusion as most studies concentrate on a single blood product and its utilisation. Patient care and blood management can be optimised by better understanding the patients who receive multicomponent transfusions. The databases Medline, EMBASE and the Cochrane Library of Systematic Reviews were searched. Observational cohort and cross-sectional studies of hospital patients reporting on multicomponent transfusion prevalence or on patient characteristics and outcomes associated with multicomponent transfusion were included. A descriptive synthesis of studies was performed. A total of 37 eligible studies were included. It was found that multicomponent transfusion prevalence varied greatly by patient population and by the combination of blood products given in the multicomponent transfusion. Multicomponent-transfused patients included burn, cardiac surgery, liver surgery and transplant, cancer, infectious diseases, trauma and intensive care unit patients. Five studies found associations between multicomponent transfusion and adverse health outcomes; however, these findings are likely confounded by indication. The overall quality of evidence was low given a fair-to-poor individual study quality, inconsistent multicomponent transfusion prevalence estimates and confounding by indication. Further research is needed to better understand the epidemiology of multicomponent transfusion, including studies on multicomponent transfusion in haematological cancer patients and studies looking for patient characteristics that can better predict multicomponent transfusion need.