Significance and implications of FHIT gene expression and promoter hypermethylation in acute lymphoblastic leukemia (ALL).

BACKGROUND: Fragile histidine triad (FHIT) has been documented to play a vital role in various cancers including acute lymphoblastic leukemia (ALL). Keeping in view the plausible role of FHIT gene, we aimed to examine DNA promoter hypermethylation and mRNA expression in ALL cases in Kashmir (North India). METHODS: A total of 66 cases of ALL were analyzed for FHIT mRNA expression and promoter methylation by qRT-PCR and Methylation Specific-PCR (MS-PCR) respectively. RESULTS: FHIT mRNA expression showed significantly decreased expression in ALL cases with mean fold change of 9.24 ± 5.44 as compared to healthy controls (p = 0.01). The pattern of FHIT deregulation in ALL cases differed significantly between decreased and increased expression (p < 0.0001). A threefold decreased expression was observed in 75% of ALL cases than healthy controls (- 3.58 ± 2.32). ALL patients with FHIT gene promoter hypermethylation presented significantly higher in 80% (53/66) of cases (p = 0.0005). The association of FHIT gene hypermethylation and its subsequent expression showed FHIT mRNA expression as significantly lower in ALL cases with hypermethylation (p = 0.0008). B-ALL cases exhibited a highly significant association between the methylation pattern and its mRNA expression (p = 0.000). In low range WBC group, a significant association was found between increased expression (26%) of the cases and methylated (4%)/unmethylated group 86% (p = 0.0006). CONCLUSION: The present study conclude that FHIT gene hypermethylation and its altered expression may be linked in the pathogenesis of ALL and provide an evidence for the role of FHIT in the development of ALL.

Left ventricular diastolic function and cardiotoxic chemotherapy.

BACKGROUND: Left ventricular ejection fraction falls when the myocardium has already lost a significant portion of its functional capacity. There are conflicting data on whether diastolic dysfunction precedes systolic dysfunction after cardiotoxic chemotherapy. We aimed to study systolic and diastolic dysfunction after cardiotoxic chemotherapy and whether diastolic dysfunction can predict subsequent risk of systolic dysfunction. It was an observational prospective cohort study, and patients receiving cardiotoxic chemotherapy were included. Baseline, demographic, and clinical details were recorded. Echocardiographic measurements of left ventricular systolic function, global longitudinal strain, and diastolic function were noted at baseline, three months, and 6 months. RESULTS: We included eighty patients. The mean age of the patients was 54.92 ± 7.6 years, predominantly females (80%). The mean left ventricular ejection fraction fell from 64.92 ± 1.96 to 60.97 ± 4.94 at 6 months. Low ejection fraction was seen in 8 (10%) patients at 6 months. The mean global longitudinal strain (GLS) at baseline was - 18.81 ± 0.797 and fell to - 17.65 ± 2.057 at 6 months, with 12 (15%) patients having low GLS (< - 18). Grade 1 diastolic dysfunction was seen in 22 (27.5%) patients, and grade 2 diastolic dysfunction was seen in 3 (3.8%) patients at 6 months. There was a significant decrease in E/A ratio (inflow early diastolic velocity/Inflow late diastolic velocity), mitral tissue Doppler velocity, and an increase in isovolumic relaxation time, mitral valve deceleration time, and E/e' (inflow early diastolic velocity/tissue Doppler mitral annular velocity), at three months and 6 months. Ejection fraction at 6 months was significantly and negatively correlated with diastolic dysfunction at three months (r = - 0.595, p = 0.02). CONCLUSIONS: Cardiotoxic chemotherapy is associated with early diastolic dysfunction. Early diastolic dysfunction predicts subsequent left ventricular systolic dysfunction.

Evaluation of chromosome 1p/19q deletion by Fluorescence in Situ Hybridization (FISH) as prognostic factors in malignant glioma patients on treatment with alkylating chemotherapy.

BACKGROUND: Either deletion or co-deletion of chromosomal arms 1p or 19q is a characteristic and early genetic event in oligodendroglial tumors that is associated with a better prognosis and enhanced response to therapy. Information of 1p/19q status is now regarded as the standard of care when managing oligodendroglial tumors for therapeutic options in anticipation of the increased survival and progression-free survival times associated with it. Keeping this in view, we first time attempted to establish the FISH based detection of 1p/19q deletion in glioma tissue samples to evaluate its role and involvement in the disease. METHOD: Overall 39 glioma cases of different histologies were evaluated by fluorescence in situ hybridization (FISH) technique using specific FISH probes with Olympus BX43 fluorescent microscope to detect chromosomes 1p and 19q or co-deletions therein. RESULTS: Of the 39 glioma samples, overall 27 (69.2%) were found to have deletion either in 1p, 19q or both. Deletions were observed in 23.0%, 7.6% and 38.4% in 1p, 19q and 1p/19q co-deletions respectively. Overall oligidendrioglioma presented with 53.8% (21 of 39) deletions, astrocytoma group showed 12.8% and GBM accounted for 2.5% deletions. Overall survival and disease free survival was seen significantly better in oligidendrioglioma and astrocytoma with deleted tumors as compared to non-deleted ones (p<0.05). CONCLUSION: Allelic losses on 1p and 19q, either discretely or shared, were more frequent in classic oligodendrogliomas than in either astrocytoma or Glioblastoma with better survival and response to therapy.

Squamous Cell Carcinoma Lung with Skeletal Muscle Involvement: A 8-year Study of a Tertiary Care Hospital in Kashmir.

AIMS: Lung cancer is the most common malignancy throughout the world. Nonsmall cell lung cancer (NSCLC) is the most common type, and squamous cell type is most common in India. Mostly, patients present with chest-related symptoms and signs. Isolated skeletal muscle metastasis (ISMM) is rarely seen. The aim was to see muscle metastasis and its prognosis. MATERIALS AND METHODS: We are presenting our data of 8 years about this common malignancy with relation to muscle metastasis, either alone or with other system metastasis. RESULTS: Muscle metastasis is seen 1.5% of patients, with male: female of 8:1. Overall median survival was 15 months and progression-free survival was 12 months. CONCLUSION: One peculiarity seen was ISMM with no pulmonary system and severe paraneoplastic hypercalcemia. Local therapy may be having an impact on overall survival in metachronous muscle involvement.

Experience of 100 solid organ transplants over a five-yr period from the first successful pediatric multi-organ transplant program in India.

To analyze the clinical profile and outcome of pediatric patients who had undergone a liver and/or RT at our center over a five yr period, case records of all the patients who had undergone a liver or RT were analyzed retrospectively. One hundred solid organ transplants were performed at our center between January 2007 and January 2012. These included 50 liver, 44 renal, one sequential liver and renal, and two CLKT. BA was the most common indication for an LT (38%). At a median follow-up of two yr three months, the patient survival was 88%. The most common indication for an RT was chronic glomerulonephritis (54.5%). At a median follow-up of three yr, the survival was 91%. The CLKT were performed for hyperoxaluria. Two yr post LT, a sequential RT was performed for ESRD resulting from transplant associated microangiopathy. All patients received a living related graft. The common post-operative complications were infections, vascular complications, and graft dysfunction. Survival rates for liver and RT at our center are comparable to those in the established centers in the West.