Association of genetic polymorphism of GSTT1, GSTM1 and GSTM3 in COPD patients in a north Indian population

Environmental exposures and genetic susceptibility can contribute to lung function decline in chronic obstructive pulmonary disease (COPD). Cigarette smoking is the main etiological factor for decline in lung function in COPD. However, only 10-20% chronic smokers develop symptomatic COPD. Genetic susceptibility to COPD might depend upon the variation of enzyme activities that detoxify cigarette smoke components. We performed a case control study to assess the association of Glutathione- S-transferase T1(GSTT1),Glutathione- S-transferase M1 (GSTM1), and Glutathione-S-transferase M3(GSTM3) common polymorphisms with the susceptibility to COPD patient in a north India population. In the present study, the genotypes of 412 subjects, (204 COPD patients and 208 healthy controls) were analyzed. Statistical analysis revealed that the frequency of homozygous GSTM1 null genotype was found to be significant higher in COPD patients as compared with healthy controls (OR, 2.58; 95% CI, 1.73-3.84; P = 0.001), but there were no significant differences in the distribution of homozygous null GSTT1 and 3-bp deletion polymorphism (rs1799735) in intron 6 variant allele in GSTM3 between COPD patients and healthy controls. Our study results suggest that GSTM1 null polymorphism is associated with genetic susceptibility to COPD. Moreover, we also found association between this polymorphism with pulmonary function test in smokers as well as nonsmokers.     

Treatment of diffuse large B-cell lymphoma

A review of new or emerging ideas concerning diffuse large B-cell lymphomas (DLBCL) is presented with particular emphasis on histologic classification, genetic prognostic factors, and first-line treatments. This lymphoma rests the most heterogeneous of all lymphomas for its clinical characteristics and outcome. This heterogeneity is probably secondary to the fact that a large proportion seems to occur from a transformation of an unknown indolent lymphoma. Current treatment is based on the combination of chemotherapy including cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) or dose-intense CHOP-like regimen, and rituximab (R-CHOP).     

Drug resistance in diffuse large B-cell lymphoma

Despite significant advances in the treatment of diffuse large B-cell lymphoma (DLBCL), drug resistance remains a major cause of treatment failure. Early strategies to improve outcome were mostly empiric or relied on classical mechanisms of drug resistance and were largely unsuccessful. More recent approaches have been aided by an understanding of the molecular pharmacology of drug action and tumor biology. Microarray profiling in particular has provided important insights into the complex biology of DLBCL and has led to a molecular taxonomy based on cell of origin and pathways of lymphomagenesis. It is now recognized that drug resistance is a complex and dynamic process related to cell cycle and apoptotic pathways, cellular differentiation, and the microenvironment. Drugs that target potential pathways of drug resistance, such as nuclear factor kappaB (NFkappaB), cyclin-dependent kinases (CDKs), and BCL-2 have entered clinical trials. However, the complexity of drug resistance requires that future clinical trials incorporate molecular translational endpoints to help identify the biologic basis of treatment failure.     

Microarray-based classification of diffuse large B-cell lymphoma

OBJECTIVE: Hierarchical clusterings of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures have previously been used to classify DLBCL into Germinal Center B-cell (GCB) and Activated B-cell (ABC) types. To examine if it was feasible to perform a cross-platform validation on the Affymetrix HG-U133A oligonucleotide arrays and improve the classification, we determined the expression profiles of pretreatment, diagnostic samples from 52 primary nodal DLBCL. METHODS AND RESULTS: First, three previously published gene lists were converted to the HG-U133A probe sets and used for hierarchical clustering. In this way, three subtypes, including the GCB type (n = 20), the ABC type (n = 25) and an intermediate group, Type-3 (n = 5), were distinguished. The CD10 and Bcl-6 expression as well as t(14;18) translocation were prevalent, but not exclusive to the GCB type. By contrast, MUM1 was only expressed in the ABC and in Type-3 samples. The 5-year survival was similar between the groups, but GCB patients showed a better initial response to CHOP or CHOP-like regimens than the remaining patients and tended to have less advanced disease and lower IPI scores. As a next step, an improved set of classifier genes was generated by analysis of 34 patients that were consistently classified as GCB or ABC in the above analyses. Seventy-eight genes were selected and demonstrated on two previously published data sets (Shipp et al. Nat Med 2002;8:68-74 and Houldsworth et al. Blood 2004;103:1862-1868) to exhibit a higher specificity than the original gene lists. CONCLUSION: We conclude that gene expression profiling with Affymetrix Genechips is efficient to distinguish between GCB and ABC types of DLBCL and that these are likely to represent separate biological entities. The Genechip platform is highly standardised and therefore useful for future prospective investigations to establish the value of gene expression profiling in the clinical management of DLBCL.     

Mastocytosis and diffuse large B-cell lymphoma, an unlikely combination

Systemic mastocytosis may be accompanied by a second haematological malignancy, usually of myeloid origin. However, a number of case reports describe systemic mastocytosis coexisting with a second haematological malignancy of lymphoid origin. Here, we report a case of a 74-year-old man with systemic mastocytosis who developed a diffuse large B-cell lymphoma. A short overview of the literature concerning mastocytosis accompanied by a second haematological malignancy is presented.     

Systemic neurolymphomatosis complicated in diffuse large B-cell lymphoma

A 73-year-old woman was diagnosed with diffuse large B-cell lymphoma of the uterus (Stage IVB). After 3 courses of CHOP therapy, right abducens nerve paralysis appeared and was diagnosed as central nervous system infiltration with lymphoma cells. Although partial remission was obtained by chemotherapy with methotrexate, numbness and muscle weakness of all four limbs appeared asymmetrically and progressed subacutely. Nerve conduction velocity examination revealed mononeuritis multiplex, but we could not reach a final diagnosis. Steroid pulse therapy, chemotherapy including high-dose methotrexate, and radiation therapy were ineffective. On autopsy, histological examination of the peripheral nerves revealed systemic neurolymphomatosis.     

Primary diffuse large B-cell lymphoma of the stomach

The stomach is the extranodal site most commonly involved by non-Hodgkin lymphomas. Diffuse large B-cell lymphoma is the most common histotype category arising in this organ. This is an aggressive lymphoma usually presenting as limited disease, being associated or not to Helicobacter pylori infection and mucosa-associated lymphoid tissue-type areas. Histopathological characteristics are similar to those reported for other diffuse large B-cell lymphomas. It occurs more frequently in males with a median age ranging between 50 and 60 years. With an adequate therapeutic strategy, its prognosis is good, with a 5-year overall survival near to 90%. Conservative treatment with anthracycline-containing chemotherapy, followed or not by involved-field radiotherapy has replaced gastrectomy as standard approach against this malignancy. Several questions on the best treatment remain unanswered. Among others, the role of rituximab, consolidation radiotherapy as well as of more conservative approaches like H. pylori-eradicating antibiotic therapy should be better defined.