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 lymphomas (DLBCLs) and Burkitt lymphoma (BL) account for the majority of aggressive lymphomas in adults and children. DLBCLs exhibit marked biological heterogeneity and variable clinical presentation and clinical course. Conversely, BL is genetically relatively homogeneous but associated with variable clinicopathological features. In this article, the authors summarize the recent advances pertaining to these B-cell neoplasms, following the latest World Health Organization classification and focusing on changes introduced since the previous edition. These changes include the addition of variants and subgroups of DLBCLs and "borderline" categories for high-grade B-cell neoplasms that show features intermediate between DLBCL and classical Hodgkin lymphoma, or between DLBCL and BL. In particular, the diagnostic and therapeutic problems related to neoplasms with features intermediate between DLBCL and BL will be discussed.
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PMID:Diffuse large B-cell lymphomas and burkitt lymphoma. 1957 70

Diffuse large B-cell lymphoma (DLBCL) forms a heterogeneous collection of aggressive non-Hodgkin's Lymphoma in which three principle classes of neoplasia have been defined according to gene expression and immunophenotyping studies. The present investigation sought to examine the immunophenotype of proposed subgroups and relate these to patient survival. A series of 155 DLBCL treated uniformly with anthracycline therapy in clinical trials, were stratified upon the basis of common biomarker expression with combination immunophenotype being related to patient overall survival. Stratification of tumours with respect to combined expression profiles of the three biological markers (CD10, Bcl-6 and MUM-1) revealed six groups showing significant differences in survival (p=0.014). The greatest difference resided between distinct populations of germinal centre (GC) cell tumours; the first being CD10-, Bcl-6+, MUM-1- and the second CD10+ Bcl-6+ MUM-1+ (p=0.002). The former group displayed median survival time of 143 months, the latter only 11 months. A third population of GC tumours (CD10+ Bcl-6+ and MUM-1-) also displayed a relative short median survival (32 months). Of the three groups presenting a non-GC or activated B cell (NGC/ABC) phenotype, only one (CD10-, Bcl-6+ and MUM-1+) presented short-term median survival (27 months) comparable with poor prognosis GC sub-populations. Within the remaining ABC tumour groups (CD10- Bcl-6- MUM-1- and CD10- Bcl-6- MUM-1+) patients presented intermediate median survival times of 54 and 58 months, respectively. Thus, the GC phenotype did not act as a universal indicator of good clinical prognosis, but rather multiple groups of GC tumours were associated with distinct overall survival profiles. Ultimately, the data allowed definition of a predictive algorithm defining three groups predicting poor, intermediate and good clinical prognosis. The first of these comprised two patient sub-populations with GC-like tumours together with one sub-population of NGC/ABC, the second two sub-populations of ABC-like tumours, and the final a single group of GC-like tumours associated with optimal long-term survival.
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PMID:Immunophenotyping of diffuse large B-cell lymphoma (DLBCL) defines multiple sub-groups of germinal centre-like tumours displaying different survival characteristics. 1978 48

Non-Hodgkin lymphomas (NHL) represent a frequent complication of human immunodeficiency virus (HIV) infection. To elucidate HIV-NHL pathogenesis, we performed a genome-wide DNA profiling based on a single nucleotide polymorphism-based microarray comparative genomic hybridization in 57 HIV-lymphomas and, for comparison, in 105 immunocompetent diffuse large B-cell lymphomas (IC-DLBCL). Genomic complexity varied across HIV-NHL subtypes. HIV-Burkitt lymphoma showed a significantly lower number of lesions than HIV-DLBCL (P = 0.032), whereas the median number of copy number changes was significantly higher in Epstein-Barr virus negative (EBV-) HIV-DLBCL (42.5, range 8-153) compared to EBV+ cases (22; range 3-41; P = 0.029). Compared to IC-DLBCL, HIV-DLBCL displayed a distinct genomic profile with no gains of 18q and specific genetic lesions. Fragile sites-associated genes, including FHIT (FRA3B), WWOX (FRA16D), DCC (FRA18B) and PARK2 (FRA6E) were frequently inactivated in HIV-NHL by interstitial deletions, and a significantly higher prevalence of FHIT alterations was observed in HIV-DLBCL compared to IC-DLBCL. The same genes involved by fragile site deletions were also frequently affected by aberrant methylation of regulative regions.
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PMID:Genome wide DNA-profiling of HIV-related B-cell lymphomas. 1983 7

We present chest x-ray, chest CT, and FDG PET images of a patient diagnosed with endobronchial lymphoma. The commonly involved thoracic structures in non-Hodgkin lymphoma are mediastinal lymph nodes. Non-Hodgkin lymphoma involving the tracheobronchial tree is rare. Localized primary endobronchial lymphoma confined to the tracheobronchial tree with no dissemination classified as type-2 is extremely rare. This is a report describing the type-2 endobronchial DLBCL. The patient also had a history of rheumatoid arthritis and was treated with methotrexate for 10 years. The other interesting aspect of this case is its association with rheumatoid arthritis and methotrexate treatment. Although there are reports documenting this type of association in the literature, there is almost no documented evidence of this association specifically with type-2 endobronchial non-Hodgkin lymphoma.
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PMID:Type two or localized endobronchial non-Hodgkin lymphoma. 1989 95

Drug metabolizing genes are involved in the detoxification of chemical carcinogens. Polymorphisms in drug-metabolizing genes affect the risk of some forms of cancer. We analyzed six polymorphisms to evaluate their association with risk for non-Hodgkin lymphoma (NHL), and to examine whether smoking modifies these associations in population-based study in Korea (713 cases and 1,700 controls). The GSTP1 rs1695 AG and the combined AG/GG genotypes were associated with decreased risk of NHL (odds ratio (OR)(AG) = 0.67, 95% confidence interval (CI) = 0.55-0.82; OR(AG/GG) = 0.66, 95% CI = 0.54-0.80) and DLBCL (OR(AG) = 0.63, 95% CI = 0.49-0.82; OR(AG/GG) = 0.64, 95% CI = 0.50-0.82). For T-cell lymphoma, only the combined AG/GG genotype was associated with decreased risk (OR(AG/GG) = 0.65, 95% CI = 0.44-0.96). The CYP1A1 rs1048943 AG genotype and the combined AG/GG genotypes were associated with increased risk of NHL (OR(AG) = 1.28, 95% CI = 1.07-1.54; OR(AG/GG) = 1.26, 95% CI = 1.06-1.51) and DLBCL (OR(AG) = 1.32, 95% CI = 1.04-1.66; OR(AG/GG) = 1.30, 95% CI = 1.03-1.63), but not T-cell lymphoma. Smoking does not modify the association between these polymorphisms and NHL risk. Our data provide evidence that the GSTP1 rs1695 and the CYP1A1 rs1048943 genotypes affect the risk of NHL in Korea.
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PMID:Polymorphisms of drug-metabolizing genes and risk of non-Hodgkin lymphoma. 1989 30

Diffuse large B-cell lymphoma (DLBCL) is the most common type of adult non-Hodgkin lymphoma and is treated with chemotherapy in combination with rituximab. Despite this aggressive therapy, the disease is fatal in 30-40% of patients. Inhibition of the apoptosis signalling pathways is strongly related to response to chemotherapy and eventual clinical outcome. In order to survive, lymphoma cells depend on disruption of the apoptosis pathway by mutations in apoptosis inducing genes or by continuous expression of anti-apoptotic proteins. The development of molecules targeting these apoptosis inhibitors provides a very promising opportunity to specifically target tumour cells without toxicity to non-malignant cells in DLBCL patients. Sensitivity for most of these antagonists can be predicted based on biological markers, suggesting the possibility of pre-defining patients who will most likely benefit from these targeted therapies. Experimental therapies aimed at restoring the upstream apoptosis pathway or targeting apoptosis inhibitors are currently being tested in clinical trials and are expected to be effective particularly in chemotherapy-refractory DLBCL, providing hope for patients who are refractory to current therapies.
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PMID:Molecular targeted therapies for diffuse large B-cell lymphoma based on apoptosis profiles. 2008 81

Class III beta-tubulin (TUBB3) expression in carcinoma is associated with resistance to tubulin-binding chemotherapeutic agents. Recently, follicular dendritic cells (FDCs) were reported to express TUBB3 under physiologic conditions. We investigated TUBB3 expression in a wide range of lymphoproliferative disorders using immunohistochemistry. Dual immunostaining for Bcl-6 and TUBB3 revealed that some germinal center B cells also express TUBB3 in addition to FDCs. In Hodgkin lymphomas (HLs), 47.1% (40/85) expressed TUBB3 in the tumor cells with an all-or-none pattern. TUBB3 expression in HL was more common in mixed cellularity type than nodular sclerosis type (P=0.032). Among non-HLs, 79.3% (23/29) of anaplastic large cell lymphoma (ALCL), 8% (2/25) of extranodal natural killer/T-cell lymphoma, and 75% (21/28) of Burkitt lymphoma showed TUBB3 expression with an all-or-none pattern. Of diffuse large B-cell lymphoma, 15.2% (32/210) expressed TUBB3 in a heterogeneous pattern. In ALCL, TUBB3 expression was more common in systemic ALCL than in primary cutaneous ALCL (P=0.046). Diffuse large B-cell lymphomas with a germinal center B-like subgroup exhibited TUBB3 expression more frequently than non-GCB-like subgroup (P=0.01). Otherwise, none of the 18 angioimmunoblastic T-cell lymphomas; 18 peripheral T-cell lymphomas, not otherwise specified; 12 follicular lymphomas; 62 marginal zone lymphomas; 7 mantle cell lymphomas; 8 small lymphocytic lymphomas; or 2 FDC sarcomas expressed TUBB3. In angioimmunoblastic T-cell lymphoma and Castleman disease, TUBB3 was positive in immunoblasts corresponding to Epstein-Barr virus-infected or Kaposi sarcoma herpes virus-infected cells. A variety of neoplastic and non-neoplastic lymphoproliferative disorders exhibited characteristic TUBB3 expression patterns; these results suggest potential for diagnostic utility, some insight into the pathobiology of TUBB3 expression, and potential therapeutic implications.
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PMID:Class III beta-tubulin shows unique expression patterns in a variety of neoplastic and non-neoplastic lymphoproliferative disorders. 2022 May 12

Genome-wide association and candidate gene studies implicate different genetic variants within the 6p21 chromosomal region with different non-Hodgkin lymphoma (NHL) subtypes. Complementing these efforts, we conducted human leukocyte antigen (HLA) class I and class II genotyping among 610 NHL cases and 555 controls of non-Hispanic white descent from a US multicenter study. Allele-disease associations were assessed by logistic regression for NHL and its subtypes. Statistically significant associations between HLA and NHL subtypes include HLA-DRB1*0101 for follicular lymphoma (odds ratio [OR] = 2.14, P < .001), HLA-DRB1*0401 for diffuse large B-cell lymphoma (DLBCL; OR = 0.45, P = .006), and HLA-DRB1*13 and follicular lymphoma (OR = 0.48, P = .008). We further observed significant heterozygote advantage for HLA class I alleles and NHL, and particularly DLBCL (P trend = .01 for elevated risk with increasing number of homozygous alleles). Our results support a role for HLA in the etiology of NHL and its subtypes.
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PMID:Human leukocyte antigen class I and II alleles in non-Hodgkin lymphoma etiology. 2038 91

Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL) and accounts for 30%to 40%of NHL. Molecules targeting nuclear factor-kappaB (NF-kappaB) are expected to be of therapeutic value in those tumors where NF-kappaB seems to play a unique survival role such as activated B-cell (ABC)-subtype DLBCL. We previously generated a rGel/BLyS fusion toxin for receptor-mediated delivery of the rGel toxin specifically to malignant B cells. In this study, we examined this fusion toxin for its ability to suppress DLBCL growth in vitro and in vivo. rGel/BLyS was specifically cytotoxic to DLBCL lines expressing all three BLyS receptors and constitutively active NF-kappaB. Treatment with rGel/BLyS induced down-regulation of the phosphorylation of inhibitory subunit of NF-kappaB (IkappaB-alpha), inhibition of NF-kappaB DNA-binding activity, and accumulation of IkappaB-alpha. In agreement with these results, we additionally found that rGel/BLyS downregulated levels of several NF-kappaB targets including Bcl-xL, Mcl-1, survivin, and x-chromosome linked inhibitor-of-apoptosis. Treatment also induced up-regulation of Bax and apoptosis through caspase-3 activation and poly ADP-ribose polymerase cleavage. Importantly, rGel/BLyS significantly inhibited tumor growth (P < .05) in a DLBCL xenograft model. Thus, our results indicate that rGel/BLyS is an excellent candidate for the treatment of aggressive NHLs that are both dependent on NF-kappaB and are resistant to conventional chemotherapeutic regimens.
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PMID:The rGel/BLyS fusion toxin inhibits diffuse large B-cell lymphoma growth in vitro and in vivo. 2045 8

The lysosomal protease Cathepsin D (CD) has been implicated in the homeostasis of lymphatic tissues. We investigated whether the level of CD expression influences the progression and the clinical outcome in Non-Hodgkin's Lymphomas (NHLs). The expression of CD was assessed by immunohistochemistry and immunofluorescence in biopsies of Diffuse Large B Cell Lymphomas (DLBCL, 35 cases), Follicular Lymphomas (FL, 9 cases of grade I-II plus 14 cases of grade IIIB), Chronic Lymphocytic Leukaemias (CLL, 17 cases) and Peripheral T-cell Lymphomas (PTCL, 5 cases). CD staining showed a cytoplasmic punctate pattern compatible with its lysosomal localization. Based on the level of CD expression and the proportion of positive cells, lymphomas were classified as 'low expressing' (< 20% of tumor cells) or 'highly expressing' (>or= 20% of tumor cells). Lymphomas highly expressing CD were associated with a worse stage (III-IV) at diagnosis (31/34 cases; p=0.002) and with a poor clinical outcome (i.e., partial remission and death; 28/34 cases; p=0.03). In the subgroup of aggressive/high grade of malignancy lymphomas (i.e., DLBCL, FL IIIB and PTCL), the Kaplan-Meier curve revealed a very low cumulative overall survival probability (approximately 20% at 5 year) for patients bearing a NHL with > 40% CD-positive cells compared to that of patients bearing a NHL with < 20% CD-positive cells ( approximately 70% at 5 year). This correlation was statistically significant (log-rank test, p=0.01). In Cox multivariate analysis CD failed to be a prognosticator independent of pathologic stage, though the hazard ratio confirmed the association of low expression with a better survival probability. These data indicate that the presence of a high percentage of CD-positive tumor cells negatively reflects on the progression of NHLs.
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PMID:High expression of cathepsin D in non-Hodgkin's lymphomas negatively impacts on clinical outcome. 2053 2


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