Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.1.1.27 (lactate dehydrogenase)
29,211 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene for the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), which is closely related with cellular sensitivity to alkylating agents, is inactivated by promoter hypermethylation in several human cancers, including malignant lymphoma. Promoter hypermethylation of the MGMT gene is a favorable prognostic factor in diffuse large B-cell lymphoma (DLBCL). Although inactivation of the MGMT gene is closely related to p53 gene mutations in several cancers, the relationship between p53 gene mutation and MGMT inactivation in malignant lymphoma has not been thoroughly examined. We studied the correlation between MGMT hypermethylation and p53 mutation in DLBCL and their impacts on patient prognosis. In a retrospective cohort study, we used a methylation-specific polymerase chain reaction technique to analyze the methylation status of the promoter region of the MGMT gene in 116 DLBCL patients who received cyclophosphamide as part of multidrug combination chemotherapies. Denaturing high-performance liquid chromatography and direct sequencing were used to search for p53 gene mutations in exons 5 through 9 in 96 of the 116 samples. Disease-free survival and overall survival were estimated by the Kaplan-Meier method. Multivariate survival analyses were performed with the Cox proportional hazards model. Forty-five (38.8%) of 116 DLBCL patients showed MGMT promoter hypermethylation. The presence of MGMT hypermethylation was associated with better overall survival (P = .036). MGMT promoter hypermethylation was a prognostic factor that was independent of established prognostic factors, such as age, disease stage, serum lactic dehydrogenase level, and the number of extranodal disease sites (hazard ratio, 2.43; 95% confidence interval, 1.28-4.61; P = .007). p53 mutations were detected in 19 (19.8%) of 96 patients and were identified as a risk factor in the complete remission rate and overall survival (P = .0040, and P = .027, respectively). A correlation between MGMT hypermethylation and p53 mutation or p53 G:C-to-A:T mutation was not observed (P = .88, and P = .31, respectively). MGMT promoter hypermethylation and p53 mutation are useful prognostic markers in DLBCL. The impact of MGMT inactivation on p53 mutation in DLBCL is unclear.
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PMID:Promoter hypermethylation of the DNA-repair gene O6-methylguanine-DNA methyltransferase and p53 mutation in diffuse large B-cell lymphoma. 1705 Feb

The study was aimed to investigate the BCL-XL expression and mutation, and its clinical significance in non-Hodgkin's lymphoma. Lymphoma cells were selectively isolated by laser microdissection. BCL-XL expression from lymphoma tissue and microdissected lymphoma cells was measured by using real-time quantitative reverse transcription-polymerase chain reaction. BCL-XL mutation was analyzed by using direct sequencing of PCR products. The results showed that compared to 15 patients with reactive hyperplasia, BCL-XL was overexpressed in follicular lymphoma (n = 30), both in lymphoma tissue (P = 0.0064) and in microdissected lymphoma cells (P < 0.0001). No significant rise of BCL-XL expression was observed in patients with T-cell lymphoma (n = 24) and diffuse large B cell lymphoma (n = 24). In follicular lymphoma, high BCL-XL level was associated with multiple extranodal involvement (P = 0.0004), elevated lactate dehydrogenase level (P = 0.0019), high-risk international prognostic index (P = 0.0013) and a short overall survival time (P = 0.0451). Mutation analysis revealed one synonymous mutation (Codon 109 ACA-->ACC) in one case of follicular lymphoma patient. It is concluded that BCL-XL expression is closely correlated with progress of follicular lymphoma and prognosis of patients with follicular lymphoma. The value of BCL-XL expression as a prognostic marker in follicular lymphoma should be considered.
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PMID:[BCL-XL expression and mutation in non-Hodgkin's lymphoma]. 1709 86

To clarify the clinicopathologic significance of a loss of CD19 expression in diffuse large B-cell lymphoma (DLBCL), we evaluated CD19 expression immunohistochemically in frozen sections from 227 patients who had received diagnoses of DLBCL according to the World Health Organization classification between 1987 and 2002. Histopathologic features of patients with CD19- DLBCL were reviewed, and their clinical features, immunophenotypes, and prognoses were compared retrospectively with respect to CD19 expression. CD19 expression was positive in 205 patients (90%). The 22 patients with CD19- DLBCL had a median age of 63 years, and the male-female ratio was 11:11. Compared with patients with CD19+ DLBCL, those with CD19- DLBCL more frequently showed elevated lactate dehydrogenase (LDH) levels (73%, P= .011). Morphologically, 15 (79%) of the 19 CD19- DLBCL patients examined showed plasmablastic/plasmacytoid differentiation. Patients with CD19- DLBCL expressed BCL2 protein less frequently than CD19+ DLBCL (P= .042). Especially noteworthy is that half of the patients with CD19- DLBCL died within 2 years after diagnosis. The CD19- DLBCL group showed a survival curve significantly inferior to that for the CD19+ group (P= .034, generalized Wilcoxon test). Our findings demonstrate that loss of CD19 expression in DLBCL is associated with elevated serum LDH levels and a poor prognosis, especially during the early follow-up period.
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PMID:Clinicopathologic significance of loss of CD19 expression in diffuse large B-cell lymphoma. 1726 1

A 63-year-old male presented with fever and general malaise in June 2004. On admission hepatosplenomegaly was apparent, but without lymphadenopathy. The laboratory examination revealed pancytopenia and increased levels of lactate dehydrogenase, direct bilirubin and soluble interleukin-2 receptor. Histological analysis of the bone marrow biopsy specimen demonstrated proliferation of atypical lymphoid cells positive for CD20 in the small capillaries, leading to the diagnosis of the Asian variant of intravascular large B-cell lymphoma (AIVL). The presence of rearrangement of the immunoglobulin gene confirmed the diagnosis. The patient responded well to CHOP therapy followed by seven courses of rituximab-combined CHOP therapy and has remained in complete remission up to the present. This case implies that bone marrow biopsy could be a useful examination for diagnosing AIVL and that rituximab-combinedchemotherapy could improve survival in patients with the disease.
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PMID:[Asian variant of intravascular large B-cell lymphoma diagnosed by bone marrow biopsy]. 1731 78

In diffuse large B-cell lymphoma (DLBCL), previous studies have suggested that, while concordant bone marrow (BM) involvement confers a poor prognosis, discordant BM involvement does not. Whether this correlation is independent of the non-Hodgkin lymphoma International Prognostic Index (IPI) was previously unknown. We reviewed all DLBCL case histories from 1986 to 1997 at our center with complete staging, IPI data, and follow-up. A total of 55 (11.2%) of 489 patients had BM involvement, including 29 with concordant involvement and 26 with discordant involvement. The 55 patients with BM involvement had a poor prognosis compared with the uninvolved BM group (5-year overall survival [OS], 34.5% versus 46.9%; log-rank P = .019). However, concordant involvement portended a very poor prognosis (5-year OS, 10.3%; P < .001), whereas discordant involvement did not (5-year OS, 61.5%, P value nonsignificant). Compared with the discordant subset, the concordant subset patients were older, had a higher serum lactate dehydrogenase level, and a significantly higher IPI. However, the poor survival associated with concordant BM involvement was independent of the IPI score (P = .002, Cox regression). We conclude that in patients with DLBCL, concordant but not discordant BM involvement confers a very poor clinical outcome. Furthermore, concordant BM involvement is an independent adverse prognostic factor.
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PMID:Concordant but not discordant bone marrow involvement in diffuse large B-cell lymphoma predicts a poor clinical outcome independent of the International Prognostic Index. 1747 10

The records of 34 patients diagnosed with primary small bowel non-Hodgkin's lymphoma during a 10-year period between January 1996 and December 2005, including 27 cases for which complete follow-up records were available, were studied. Abdominal pain (70.6% of patients) was the main presenting symptom, followed by intestinal obstruction (38.2%). The most common primary site was the ileum (58.8%), followed by the jejunum (26.5%) and duodenum (17.6%); one case had tumours at two sites in the small bowel. Twenty-seven patients had small bowel B-cell lymphoma (24 diffuse large B-cell lymphoma; three mucosa-associated lymphoid tissue B-cell lymphoma) and seven patients had small bowel T-cell lymphoma. Cumulative survival in patients with small bowel B-cell lymphoma was higher than that in patients with small bowel T-cell lymphoma. Data on 16 male and eight female patients with diffuse large B-cell lymphoma showed that 62.5% of these patients presented with disease stages I or II and 37.5% with stages III or IV. Cumulative survival in patients at stages IE or IIE was significantly higher than that of patients at stages IIIE or IVE. Four of five patients who died from diffuse large B-cell lymphoma had abnormal levels of lactate dehydrogenase and serum albumin.
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PMID:Primary small-bowel non-Hodgkin's lymphoma: a study of clinical features, pathology, management and prognosis. 1759 70

Disorders of the cell cycle regulatory machinery play a key role in the pathogenesis of cancer. Over-expression of cyclin D1 protein has been reported in several solid tumors and certain lymphoid malignancies, but little is known about the effect of its expression on clinical behavior and outcome in B-cell Non-Hodgkin lymphoma (NHL). In this study, we investigated the expression of cyclin Dl in group of patients with NHL and correlated the results with the clinical and laboratory data. The degree of expression of cyclin Dl protein was evaluated by flow cytometry in a group of NHL patients (n = 46) and in normal control group (n = 10). Cyclin Dl over expression was detected in 10 out of 46 (21.7%) patients; they were 5/5-mantle cell lymphoma (MCL) (100%) and 5/28 large B-cell lymphoma (17.8%). All other NHL subtypes showed normal cyclin D1 expression. The clinical signs (hepatomegaly, splenomegaly and B-symptoms, clinical staging) and laboratory data (hemoglobin, white cell count (WBCs), platelet count, and bone marrow infiltration) were not significantly different between NHL subgroup with cyclin Dl over expression and that with normal cyclin Dl expression. Serum lactic dehydrogenase (LDH) levels and lymphadenopathy were significantly higher in NHL group with cyclin D1 over expression as compared to those without. Also, cyclin D1 over expression is associated with poor outcome of NHL patients. Cyclin Dl over expression was evident among all cases of MCL and few cases of large B-cell lymphoma. Cyclin Dl over expression might be used as adjuvant tool for diagnosis of MCL; has role in NHL biology and is bad prognostic index in NHL.
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PMID:Cyclin Dl expression in B-cell non Hodgkin lymphoma. 1760 88

Astrocytes are one of the predominant glial cell types in the adult central nervous system functioning as both supportive and metabolic cells for the brain. Our objective in this experiment is to study the direct effects of hydrogen peroxide induced oxidative stress on astrocytes in culture. These astrocytes were derived from both an aged mouse strain (P8) and a matched control strain (R1). The astrocytes for both the P8 and R1 strains were treated with increasing concentrations of hydrogen peroxide. Our results showed that the oxidative stress had a similar effect in both strains of astrocytes; decreases in 3-(4,5-dimethylthiazol-2-yl)-2,2-diphenyltetrazolium bromide (MTT) and glial fibrillary acidic protein (GFAP) levels, and increases in terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL) staining, lactate dehydrogenase (LDH) staining, and superoxide dismutase (SOD), caspase-3 and B-cell lymphoma 2-associated protein X (bax) levels. At a hydrogen peroxide concentration of 400 microM , the differences of the above parameters between P8 cultures and R1 cultures were statistically significant (p<0.05). This strongly suggested that astrocytes derived from P8 and R1 strains reacted to oxidative stress with similar mechanisms and consequences. However, the mechanisms were not able to compensate for the oxidative stress in the P8 strain at a hydrogen peroxide concentration of 400 microM. The inability of the P8 astrocytes to counteract the oxidative stress might lead to inadequate protection from neuronal loss possibly resulting in significantly more astrocytic death. Our results suggested that the changes of astrocytes in peroxide detoxification may play a role in aging of the central nervous system, and further aging studies should examine the oxidative status of the samples.
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PMID:Oxidative stress on the astrocytes in culture derived from a senescence accelerated mouse strain. 1766 19

A 68-year-old man presented with systemic lymph node swelling. A biopsy specimen taken from the right cervical lymph node showed that the normal architecture was replaced by a diffuse proliferation of large lymphoid cells with large atypical nuclei. Immunohistochemical analysis showed that the atypical lymphoid cells were positive for CD5, CD10, CD20, CD79a, and Bcl2, and negative for CD3 and cyclin D1. A diagnosis of diffuse large B-cell lymphoma was made. Karyotypic findings included add(5)(q13), del(6)(q13), add(17)(p11), add(19)(p11), add(19)(p13), and t(6;14)(q15;q32). The serum lactate dehydrogenase level and indirect bilirubin level were slightly elevated. Elliptocytosis was observed in the peripheral blood, and a diagnosis of hereditary spherocytosis was made from the family history. Regarding CD5+CD10+ diffuse large B-cell lymphoma with a non-random chromosomal translocation of t(6;14)(q15;q32), studies on the mechanism of lymphomagenesis are needed.
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PMID:t(6;14)(q15;q32) in a patient with CD5+CD10+ diffuse large B-cell lymphoma. 1787 29

Improved survival has been observed in poor-risk diffuse large B-cell lymphoma (DLBCL) patients treated with high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) in first complete remission. Retrospective studies have suggested that HDT with ASCT can improve survival also in partial responders but some doubts about the advantage of intensive therapy in such patients still remain. We evaluated retrospectively the results of HDT and ASCT in 55 patients with confirmed DLBCL treated between May 1999 and July 2006. Thirty-six patients (65%) showed partial remission (PR) and 19 patients (35%) reached complete remission (CR) after induction treatment with (44%) or without (56%) concomitant rituximab (R) immunotherapy. After HDT and ASCT, 69% of patients fulfilled the criteria of CR, 22% had unconfirmed CR (CRu), 7% remained in PR and 1 patient (2%) relapsed. Twenty patients in PR after the induction treatment reached CR after ASCT, 12 other PR patients achieved CRu. The 5-year event-free survival (EFS) of the 55 transplanted patients was 76% (95% confidence interval /CI/, 63% to 89%) and the 5-year overall survival (OS) was 85% (95% CI, 73% to 97%). The EFS and OS rates differed significantly only between patients younger than 40 years and older groups (p=0.022 and p=0.046, respectively). On univariate analysis of prognostic factors, EFS and OS were not affected by any of the following: age, sex, stage, subtype of DLBCL, initial lactate dehydrogenase, beta-2-microglobulin and serum thymidine kinase levels, International Prognostic Index (IPI) and age-adjusted IPI scores, induction treatment with or without rituximab and type of primary therapeutic response (CR vs PR). These results show that first-line HDT and ASCT for adults up to the age of 65 years with poor-risk DLBCL is a feasible and effective treatment option even in the era of R-chemotherapy in CR as well as for patients in PR.
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PMID:High-dose therapy and autologous stem cell transplantation in patients with diffuse large B-cell lymphoma in first complete or partial remission. 1834 54


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