Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diffuse large B-cell lymphoma in the Revised European-American Lymphoma Classification encompasses various morphologic subtypes of diffuse large-cell lymphomas of B-cell origin. The category is biologically and clinically heterogeneous, even though it constitutes approximately 30% of all non-Hodgkin's lymphomas. Clinically, the International Prognostic Index that identifies high-risk group in aggressive non-Hodgkin's lymphomas is widely accepted. Lacking, however, are biologic or molecular prognostic markers that might aid in understanding the pathogenesis and designing specific therapies. CD44 isoforms are involved in tumor dissemination and might be associated with aggressive behavior of non-Hodgkin's lymphomas. We studied immunohistochemical expression of CD44s and CD44v6 in the tumors and examined their clinical significance in a cohort of patients with primary nodal diffuse large B-cell lymphoma who were uniformly evaluated and treated with doxorubicin-containing chemotherapy (n = 42). In contrast to CD44s signals, CD44v6 signals were weak in routinely processed non-Hodgkin's lymphoma sections. Therefore, we used a highly sensitive catalyzed reporter deposition system and successfully detected CD44v6 signals in diffuse large B-cell lymphomas. Overexpression of the isoform was verified by Southern blot of reverse transcription polymerase chain reaction products. CD44s and CD44v6 were positive in 17 (40%) of 42 and 13 (31%) of 42, respectively. CD44v6 was detected predominantly in lymphoma cells, whereas CD44s was often positive for nonneoplastic small lymphocytes as well. In univariate regression analysis, the B symptoms, being in the International Prognostic Index high-risk group, and CD44v6 expression emerged as significant parameters for poorer overall survival, but CD44s expression did not achieve statistical significance. When multivariate regression analysis was performed using the former three parameters, only CD44v6 expression remained significant (P = .017; relative risk = 3.48), indicating that CD44v6 is a molecule particularly important for predicting worse prognosis. CD44v6, which can be detected in the archival materials, might be a biologically and clinically useful marker in identifying the high-risk group in the diffuse large B-cell lymphoma category of the Revised European-American Lymphoma Classification.
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PMID:Prognostic significance of CD44v6 in diffuse large B-cell lymphoma. 1034 95

In this study the authors explored the value of immunostaining for follicular center B-cell markers, BCL-6 and CD10, in paraffin sections as a tool for the differential diagnosis of B-cell lymphomas. The cases studied comprised reactive lymphoid hyperplasia (RLH; n = 19), follicular lymphoma (FL; n = 50), low-grade mucosa-associated lymphoid tissue (MALT) lymphoma (n = 24), mantle cell lymphoma (n = 19), splenic marginal zone lymphoma (n = 13), diffuse large B-cell lymphoma (DLBCL; n = 54), Burkitt's lymphoma (BL; n = 20), nodular lymphocyte predominance Hodgkin's disease (NLPHD; n = 16), and classic Hodgkin's disease (CHD; n = 13). In RLH, CD10 and BCL-6 were expressed almost exclusively by the follicular center cells. In contrast in FL, the expression of CD10 (39/50) and BCL-6 (34/36) was seen in both follicular and interfollicular neoplastic B cells. Marginal zone/MALT lymphomas and mantle cell lymphoma were always negative. In DLBCL the expression was variable for both CD10 (21/54) and BCL-6 (39/47), with some tumors, including cases of transformed follicular lymphoma (9/10), coexpressing CD10 and BCL-6, and others expressing only BCL-6, and a small group expressing neither marker, possibly reflecting the underlying primary pathogenetic events such as the rearrangement of BCL-2 or BCL-6 genes. BL was always both CD10 and BCL-6 positive. In NLPHD the L&H cells expressed BCL-6 (11/13) but not CD10, whereas in CHD BCL-6 expression was seen in half of the cases. This study demonstrates that both CD10 and BCL-6 are reliable markers of follicular center B-cell differentiation. CD10 and BCL-6 immunostaining have an important role in differential diagnosis of FL from RLH and other low-grade B-cell lymphomas. The results also suggest that a CD10/BCL-6 expression pattern may be helpful in identifying main subsets of DLBCL. However, additional studies comparing genotype with immunophenotype are required.
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PMID:CD10 and BCL-6 expression in paraffin sections of normal lymphoid tissue and B-cell lymphomas. 1084 87

Chromosomal translocation t(6;14)(p21.1;q32.3) has been reported as a rare but recurrent event not only in myeloma and plasma cell leukemia but also in diffuse large B-cell non-Hodgkin lymphoma (B-NHL) (diffuse large B-cell lymphoma [DLBCL]) and splenic lymphoma with villous lymphocytes (SLVL); however, the nature of the target gene(s) has not been determined. This study identified t(6;14)(p21.1;q32.3) in 3 cases of transformed extranodal marginal zone B-NHL, in 1 case of SLVL, and in 1 case of a low-grade B-cell lymphoproliferative disorder. In a sixth case, a CD5(+) DLBCL, the translocation was identified by molecular cloning in the absence of cytogenetically detectable change. Two chromosomal translocation breakpoints were cloned by using long-distance inverse polymerase chain reaction methods. Comparison with the genomic sequence for chromosome 6p21.1 showed breakpoints approximately 59 and 73.5 kilobases 5' of the cyclin D3 (CCND3) gene with no other identifiable transcribed sequences in the intervening region. Although Southern blotting with derived genomic 6p21.1 probes failed to detect other rearrangements, fluorescent in situ hybridization assays, using BAC (bacterial artificial chromosome) clones spanning and flanking the CCND3 locus, along with probes for IGH confirmed localization of 6p21.1 breakpoints within the same region, as well as fusion of the CCND3 and IGH loci. Furthermore, in all cases, high-level expression of CCND3 was demonstrated at RNA and/or protein levels by Northern and Western blotting and by immunohistochemistry. These data implicate CCND3 as a dominant oncogene in the pathogenesis and transformation in several histologic subtypes of mature B-cell malignancies with t(6;14)(p21.1;q32.3) and suggest that CCND3 overexpression seen in about 10% of DLBCL cases may have a genetic basis.
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PMID:Cyclin D3 is a target gene of t(6;14)(p21.1;q32.3) of mature B-cell malignancies. 1167 58

Diffuse large B-cell lymphoma (DLBCL), a histologically well-defined subset of non-Hodgkin lymphoma, is clinically and genetically heterogenous. By G-banding, most cases showed complex hyperdiploid karyotypes and diverse cytogenetic abnormalities that included recurring and nonrecurring translocations, deletions, duplications, and marker chromosomes. While G-banding provided valuable leads to identification of specific rearrangements that enabled gene discovery and clinical correlations, many aberrations remained uncharacterized because of their complexity. The molecular cytogenetic technique spectral karyotyping (SKY), on the other hand, enables complete characterization of all aberrations in a tumor cell karyotype and, hence, precise quantitation of chromosome instability. We report here, for the first time, SKY analysis of a panel of 46 DLBCL cases previously analyzed by G-banding, ascertained at the Memorial Sloan-Kettering Cancer Center. This analysis provided a cytogenetic profile of DLBCL that was characterized by a higher level of instability, qualitatively as well as quantitatively, compared with G-banding. Thus, 551 breakpoints were detected by SKY, in contrast to the 295 by G-banding. Several new recurring breakpoints, translocations, and regions of gain and loss were identified, which included 13 breakpoints not previously identified by G-banding, 10 breakpoints that were underrepresented by G-banding, and 4 previously unrecognized translocations: der(14)t(3;14)(q21;q32), t(1;13)(p32;q14), t(1;7)(q21;q22), and der(6)t(6;8)(q11;q11). We identified new clinical associations involving recurring breakpoints detected by SKY. These studies emphasize the value of SKY analysis for redefinition of chromosomal instability in DLBCL to enhance gene discovery as well as clinical correlation analysis.
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PMID:Spectral karyotyping identifies new rearrangements, translocations, and clinical associations in diffuse large B-cell lymphoma. 1189 93

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. In contrast to many other hematological malignancies, no chromosomal abnormalities with a diagnostic or prognostic value have been identified in DLBCL. Numerical chromosomal imbalances were characterized by comparative genomic hybridization (CGH) performed on 54 DLBCL tumors from a total of 40 patients. The clonal relatedness was demonstrated in 9 of 11 pairs of matched diagnostic tumors and their relapses as determined by IGH gene rearrangement analysis and/or the CGH profiles. Furthermore, immunohistochemical expression analyses of BCL2 and BCL6/LAZ3 were performed on all cases. Copy number changes were detected in 94% of the diagnostic tumor samples and in all of the relapses. Chromosomal losses in diagnostic tumors were preferentially observed at 8p22-pter (29%), 1p34-pter (26%), 6q23-qter (20%), 17p12-pter (17%) and 22q (17%), 9p23-pter (14%), whereas gains were mainly seen in Xq25-26 (43%), 13q22 (26%), 12cen-q14 (20%), 3q24-25 (11%), 7 (11%), and 18q12-21 (11%). Loss of 22q was significantly more commonly seen in the diagnostic tumor samples with more advanced clinical stage in other words, Stage III-IV compared with Stage I-II, and band 18q21 was significantly more often gained in relapses as compared to diagnostic tumors. None of the recurrent alterations were detected as a single abnormality, suggesting that other genetic lesions below the detection level of CGH may be the initiating event in the tumorigenesis of DLBCL. However, the distribution of CGH alterations support the idea of a progression of genetic events where loss of 8p and 9p and gain of 3q, 13q, and 18q would represent relatively early events because they were distributed in tumors with only two abnormalities.
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PMID:Chromosomal imbalances in diffuse large B-cell lymphoma detected by comparative genomic hybridization. 1218 Dec 65

Non-Hodgkin's lymphomas are a heterogeneous group of malignancies of the lymphoid system. The exact etiology for most lymphomas has not been determined, but both viral and bacterial infections have been shown to be important etiologic factors. The WHO classification of hematopoietic and lymphoid tumours classifies lymphomas into B-cell and T-cell neoplasms. B-cell lymphomas account for more than 85% of all lymphomas. The Ann Arbor staging classification has been adopted by the AJCC and UICC as a standard for classifying extent of anatomic disease. The two most common histologic disease entities are follicular lymphomas and diffuse large B-cell lymphomas. The management of follicular lymphomas is used as a paradigm for the management of all indolent lymphomas. Radiation therapy is used for stage I and II disease, while alkylating agent chemotherapy, immunotherapy and radioimmunotherapy are most frequently used in stage III and IV disease that requires treatment. Most patients with follicular lymphoma enjoy prolonged survival, but at present there is no evidence that those with stage III and IV follicular lymphoma can be cured. Diffuse large B-cell lymphomas serve as a paradigm for treating aggressive lymphomas. Stage I and II diffuse large cell lymphomas are generally treated with combined modality therapy with doxorubicin-based chemotherapy followed by involved field radiation therapy, while those with stage III and IV disease are treated with chemotherapy alone. Patients who fail initial management are treated with further chemotherapy. High-dose chemotherapy with stem cell rescue has been shown to be particularly effective as salvage treatment for diffuse large cell lymphomas. The management of a heterogeneous group of primary extranodal lymphomas in general follows the above treatment principles, with additional treatment being required for those with a high risk of CNS failures, or involvement of contralateral paired organs. The management of MALT lymphomas, especially gastric MALT lymphoma, deserves special attention because of the high response rate to Helicobacter pylori eradication therapy.
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PMID:Therapy of non-Hodgkin's lymphoma. 1269 88

PDX (10-propargyl-10-deazaaminopterin) is a novel anti-folate with improved membrane transport and polyglutamylation in tumor cells. In prior studies, PDX exhibited enhanced efficacy over methotrexate (MTX) in lung and breast carcinoma xenografts. Because MTX is active in the treatment of aggressive non-Hodgkin's lymphoma (NHL), we compared the efficacy of PDX and MTX against five lymphoma cell lines: RL (transformed follicular lymphoma), HT, SKI-DLBCL-1 (diffuse large B cell), Raji (Burkitt's), and Hs445 (Hodgkin's disease). After 5-day continuous in vitro exposure, PDX demonstrated > 10-fold greater cytotoxicity than MTX in all cell lines (IC50PDX = 3-5 nM, IC50MTX = 30-50 nM). We then compared the in vivo effects of anti-folates against three established human NHL xenografts in NOD/SCID mice. Tumor bearing animals were treated with saline (control) or the maximum tolerated doses of MTX (40 mg/kg) or PDX (60 mg/kg) via an intraperitoneal route twice weekly for 2 weeks. Almost 90% of HT lymphomas treated with PDX completely regressed, whereas, those treated with MTX treatment had only modest growth delays. In two other xenografts, tumor bearing mice had complete regression rates of 56% (RL) and 30% (SKI-DLBCL-1) after PDX therapy. No regressions and only minor growth inhibition was noted after MTX therapy. RT-PCR analysis for the expression of genes involved in folate metabolism demonstrated that increased sensitivity to PDX correlated with higher RFC-1 gene expression with no difference in FPGS or FPGH levels, suggesting that measurement of tumor RFC-1 gene expression level may be a predictor of response to PDX. These results demonstrate that the PDX has markedly greater potential activity against human NHL than MTX and warrants further preclinical and clinical evaluation.
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PMID:Activity of a novel anti-folate (PDX, 10-propargyl 10-deazaaminopterin) against human lymphoma is superior to methotrexate and correlates with tumor RFC-1 gene expression. 1285 5

Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 40% of all B-cell non-Hodgkin lymphomas of the Western world. According to the "WHO classification of tumours of the haematopoietic and lymphoid tissues", the term DLBCL is likely to include more than one disease entity, as suggested by the marked variability of the clinical presentation and response to treatment of this disease. Such heterogeneity may reflect the occurrence of distinct molecular subtypes of DLBCL as well as differences in the host's immune function. In immunocompetent hosts, approximately 50% DLBCL carry one of two primary molecular lesions defining two distinct genotypic subgroups, characterized by activation of either the BCL-6 or the BCL-2 proto-oncogene. Conversely, the remaining DLBCL of immunocompetent hosts display one of several molecular lesions, each associated with a small subset of cases and including activation of the proto-oncogenes REL, MUC-1, BCL-8 and c-MYC. The molecular pathogenesis of immunodeficiency-associated DLBCL differs substantially from that of DLBCL in immunocompetent hosts. In fact, EBV infection is present in a large fraction of immunodeficiency-associated DLBCL, whereas it is consistently negative in DLBCL of immunocompetent hosts, probably reflecting the critical role of disruption of the immune system in this disease. Finally, the application of DNA microarray technology to DLBCL has led to the distinction of two disease variants: a germinal center like DLBCL and an activated peripheral B-cell like DLBCL. Overall the molecular features of DLBCL may identify prognostic categories of the disease and may represent a powerful tool for therapeutic stratification.
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PMID:Molecular heterogeneity of diffuse large B-cell lymphoma: implications for disease management and prognosis. 1497 86

Studying a large series of malignant lymphoma is important to increasing our understanding of this disease. Based on the World Health Organization classification system, 1983 cases of lymphoma at Siriraj Hospital were classified as either non-Hodgkin lymphoma (NHL) (92.1%) or Hodgkin lymphoma (HL) (7.9%). The NHL cases were 75% B cell type and 25% T cell type. Diffuse large B-cell lymphoma, unspecified peripheral T-cell lymphoma, follicular lymphoma, extranodal marginal zone B-cell lymphoma, precursor T lymphoblastic lymphoma, and Burkitt lymphoma accounted for 84.3% of all NHL cases found. Mixed cellularity and nodular sclerosis types constituted 77.7% of the HL cases found. An overall male preponderance was observed, but sex distribution differed among various types of lymphoma, and a female preponderance was observed in the elderly subjects. Changes in the frequency of B-cell NHL by age were characteristic: <50% in the first decade of life, a further decrease in the second decade, >60% in the third decade, and increases thereafter, reaching 90% after the seventh decade. High frequency of follicular lymphoma in Bangkok but low frequency in the Northeastern region and high frequency of HL in the Southern region were significant (P <0.05). Extranodal involvement was observed in 58.7% of NHLs, commonly affecting the upper aerodigestive tract and gastrointestinal tract, with some differences in geographical distribution. Higher frequencies of T-cell NHLs involving extranodal sites and of B-cell NHLs involving lymph nodes were significant (P <0.05). The distribution of various types of lymphoma and comparison with other large series of lymphoma further demonstrates the heterogeneity of this disease.
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PMID:Analysis of 1983 cases of malignant lymphoma in Thailand according to the World Health Organization classification. 1499 41

Primary extranodal non-Hodgkin's lymphomas of the head and neck account for 10-20% of all non-Hodgkin's lymphomas. Primary tonsillar lymphoma accounts for less than 1% of head and neck malignancies, although the tonsil is the most common primary extranodal site of head and neck non-Hodgkin's lymphomas. In this study we analyzed our cases of tonsillar lymphoma treated in our institution during the last 10 years to compare the finding of this study with those of previous studies. We reviewed the cases of tonsillar lymphoma treated in the Radiation Oncology Department of Shiraz University from 1992 to 2002. Clinical data were obtained from patients' files. The patients were treated by combined chemotherapy [a median of six cycles of a CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisolone)] and radiation therapy (40-50 Gy to the primary site and neck). Chemotherapy mainly preceded radiotherapy, although the sequence of radiotherapy and chemotherapy was determined by individual physicians and patients' choice. Surgery was used mainly to establish the diagnosis, and tonsillectomy was performed for localized small lesions. Between 1992 and 2002, 19 patients with stage IE (10), IIE (7), and IIIE (2) disease were treated. Median and mean age was 48 and 44 years (range: 22-76 years), respectively, at the time of diagnosis, with a male to female ratio of 1.2:1. The vast majority of patients presented in early stages with aggressive histology. High-grade tumors seemed to affect mainly young people (p=0.226). Diffuse large B-cell lymphomas were the most prevalent. Male patients were significantly younger than females (p=0.021). The patients were treated by combined chemotherapy and radiation therapy. All patients achieved and maintained complete remission with a median of 60 months relapse-free survival and a 5-year cause-specific survival rate of 100%. All patients developed some degree of oropharyngeal mucositis. Three patients (16%) experienced grade 3 or 4 neutropenia. Mild (grade I) xerostomia remained persistently in four patients (21%). A late fatal side effect was observed in one patient who developed radiation-induced sarcoma 7 years after initial diagnosis and died 8 months later without evidence of recurrent lymphoma. Complete follow-up was obtained in all patients. The follow-up period ranged from 18 to 141 months with a median of 60 and a mean of 60.4 months. At the time of last follow-up, all patients but one were alive. Age, sex, stage, bulk of disease, performance status, number of chemotherapy cycles, number of involved sites, histologic subtypes, and radiation dose were analyzed as prognostically significant for disease-specific survival in our cases. Significant prognostic factors were not identified by multivariate analysis. Combined chemotherapy and radiation therapy is safe, highly effective, and probably curative for most patients with primary tonsillar lymphoma.
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PMID:Treatment results of tonsillar lymphoma: a 10-year experience. 1504 16


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