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Introduction:The FMS-like tyrosine kinase-3 (FLT3), a member of the Platelet-derived growth factor (PDGF-R) subfamily of receptor tyrosine kinases, expressed on early hematopoietic progenitor cells play an essential role in survival and differentiation of stem cell. Majority of acute myeloid leukemia (AML) patients have mutation in this gene. Two types of frequent mutations are present in this gene. Both the types FLT3-ITD and D835 mutations play an important role in prognosis of AML patients. Methods:Total 33 patients were enrolled in the study. Blood samples were collected from the subjects, from which the DNA isolation was carried out.For FLT3-ITD mutation, PCR was performed and for D835 mutation PCR-RFLP was performed. DNA segments were amplified using Polymerase Chain Reaction (PCR). Results: FLT-3 ITD mutation was detected in 12% of patients and D835 mutation was detected in 3% of patients. The study revealed significant correlation between ITD and Tdt, while D835 negatively correlated with CD33, HLADR and Tdt. However, there was no substantial correlation of D835 with LDH value. also revealed that FLT-3 ITD significantly correlated with LDH values in AML patients. The mean value of LDH was 753.45 IU/L in ITD positive patients as compared to ITD negative patients with 338 IU/L mean LDH value, suggesting higher LDH values in ITD positive. Conclusion:These Genotypic analysis of FLT-3 mutation results from West Indian population provide important tools for understanding of AML pathogenesis and determination of appropriate therapeutic intervention. Further large number of patient data can also corroborate these significant results.
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Background:The double strand break repair pathway, comprising XRCC2 and XRCC3 has crucial role in maintenance of genomic stability and prevention of tumor initiation and progression. Therefore, sequence variants of such DNA repair genes may compromise individual's DNA repair capacity and can influence risk of developing breast cancer. Method and Results:To estimate the impending effect of XRCC2 (Arg188His) and XRCC3 (Thr241Met) polymorphisms on breast cancer, 133 breast cancer patients and 154 healthy controls were evaluated by PCR-RFLP method. In the present study, it was noted that there was no significant correlation between these polymorphisms and breast cancer risk. However, within patient group, significant association of XRCC2 variants with PR negative breast cancer was detected. Further, patients with XRCC2 variant genotypes were also at high risk of developing TNBC and Her2 enriched subtypes as compared to luminal A subtype. Significant relation was also obtained between XRCC3 variants and large sized and infiltrative breast tumors. Conclusion: These noteworthy observations demonstrate potential involvement of XRCC2 and XRCC3 polymorphisms in pathophysiology of breast cancer.
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OBJECTIVE: Oral cancer is the leading malignancy in India, with tobacco playing a major role in the etiology. The aim of the present study was to quantify nitrate+nitrite (NO2+NO3) in tobacco products as well as to study tobacco exposure related biomarkers in controls, patients with oral precancers (OPC) and oral cancer patients. MATERIALS & METHODS: Healthy individuals (n=90) were grouped into without habit of tobacco (NHT, n=30) and healthy individuals with habit of tobacco (WHT, n=60). Oral cancer patients with a tobacco habit were classified into abstinence (n=62) and non-abstinence (n=64) groups according to status at the study time. Urinary nicotine and cotinine levels were analyzed by modified high-pressure liquid chromatography (HPLC) using a UV detector. Levels of NO2+NO3 in tobacco and urine, and urinary thioether levels were estimated by spectrophotometry. RESULTS: NO2+NO3 levels in different types of tobacco product ranged between 0.13 to 3.39 mg/g. The Odds Ratio (OR) analysis indicated positive associations of both smoking and chewing habits of tobacco with high risk of development of oral cancer. Urinary nicotine, cotinine and NO2+NO3 levels were significantly elevated in WHT, patients with OPC and oral cancer patients as compared with the NHT group. This was also the case for urinary thioether levels. Levels of urinary nicotine and cotinine were also higher in the non-abstinence group with oral cancers. CONCLUSION: The results confirmed that tobacco chewing and smoking habits are prominent risk factors for development of oral cancer in the western part of India (Gujarat). Urinary nicotine, cotinine, NO2+NO3 and thioether levels can be helpful for screening programs for oral cancer.