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)

The CDKN2A gene located on chromosome region 9p21 encodes the cyclin-dependent kinase-4 inhibitor p16/INK4A, a negative cell cycle regulator. We analyzed p16/INK4A expression in different types of non-Hodgkin's lymphoma to determine whether the absence of this protein is involved in lymphomagenesis, while also trying to characterize the genetic events underlying this p16/INK4A loss. To this end, we investigated the levels of p16/INK4A protein using immunohistochemical techniques in 153 cases of non-Hodgkin's lymphoma, using as reference the levels found in reactive lymphoid tissue. The existence of gene mutation, CpG island methylation, and allelic loss were investigated in a subset of 26 cases, using single-strand conformational polymorphism and direct sequencing, Southern Blot, polymerase chain reaction, and microsatellite analysis, respectively. Loss of p16/INK4A expression was detected in 41 of the 112 non-Hodgkin's lymphomas studied (37%), all of which corresponded to high-grade tumors. This loss of p16/INK4A was found more frequently in cases showing tumor progression from mucosa-associated lymphoid tissue low-grade lymphomas (31 of 37) or follicular lymphomas (4 of 4) into diffuse large B-cell lymphomas. Analysis of the status of the p16/INK4A gene showed different genetic alterations (methylation of the 5'-CpG island of the p16/INK4A gene, 6 of 23 cases; allelic loss at 9p21, 3 of 16 cases; and nonsense mutation, 1 of 26 cases). In all cases, these events were associated with loss of the p16/INK4A protein. No case that preserved protein expression contained any genetic change. Our results demonstrate that p16/INK4A loss of expression contributes to tumor progression in lymphomas. The most frequent genetic alterations found were 5'-CpG island methylation and allelic loss.
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PMID:Loss of p16/INK4A protein expression in non-Hodgkin's lymphomas is a frequent finding associated with tumor progression. 973 37

Based on concepts of the successful German-Austrian pediatric Hodgkin studies DAL-HD 78 until-90, a new trial was initiated addressing the question whether radiotherapy can be further reduced or can be omitted in case of complete remission after initial chemotherapy, aiming at reduction of sequelae after radiotherapy, especially radiogenic second malignancies. In respect to CHEMOTHERAPY patients are stratified into 3 therapy groups (TG) according to stage and gender: 2 courses of OPPA (girls) or OEPA (boys) in TG1 (stage IA/B, IIA), and in addition 2 (TG2: stage IEA/B, IIEA, IIB, IIIA) or 4 (TG3: stage IIEB, IIIEA/B, IIIB, IVA/B) COPP courses. Boys with stage IIIB and IIIEB receive OPPA instead of OEPA. RADIOTHERAPY is administered according to response to chemotherapy independent of stage: patients with complete remission or minimal residues do not receive irradiation; patients with more than 75% tumor regression are irradiated to involved fields at a dose of 20 Gy. Doses of 30 or 35 Gy are given to regions with tumor regression below 75% or residual bulky tumor of > 50 ml, respectively. INTERIM RESULTS: From 8/95 till 1/98 we registered 385 patients under the age of 18 years from Germany, Austria, Switzerland, Sweden and the Netherlands. Therapy has been completed in 334 patients. Three patients with solitary nodular paragranuloma were treated with surgery only. Out of 331 patients 89 (26.9%) achieved a complete remission with chemotherapy. Tumor regression of more than 75% was seen in 193 (58.3%) patients and below 75% in 39 (11.8%) patients. Tumor progression during chemotherapy occurred in 1 (0.3%) patient. Response after chemotherapy was not evaluable for 9 (2.7%) patients. Radiotherapy was omitted in 91 (27.1%) patients: in TG1 50 of 142 (34%) patients, TG2 24 of 98 (24.5%) patients and TG3 18 of 94 (19.2%) patients. Initially involved regions were irradiated at a dose of 20 Gy in 164 of 334 (49.1%) patients. Doses up to 30 Gy or 35 Gy were given to 19 (5.7%) or 57 (17.1%) patients respectively. Events (tumor progression, relapse or death) occurred in 23 of 334 patients until now. The event-free survival rate is 0.91 at 2 1/2 years for all study patients and 0.89 for patients without radiotherapy. Six relapses occurred in 91 patients without radiotherapy. No relapse occurred in TG1 (n = 49), but in 5 of 24 TG2-patients, and in 1 of 18 TG3 patients without radiotherapy. As yet, the results are not significantly inferior compared with trial DAL-HD 82. Therefore this trial aiming at omitting radiation therapy in patients with complete remission after a short lasting chemotherapy will be continued. Longer follow up is necessary for final evaluations and conclusions.
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PMID:[Multi-national therapy study for Hodgkin's disease in children and adolescents GPOH-DH 95. Interim report after 2 1/2 years]. 974 55

Hodgkin's disease (HD) represents a malignant lymphoma in which the putative malignant Hodgkin and Reed-Sternberg (H-RS) cells are rare and surrounded by abundant reactive cells. Single-cell analyses showed that H-RS cells regularly bear clonal Ig gene rearrangements. However, there is little information on the clinical evolution of HD in a given patient. In this study, we used the single-cell polymerase chain reaction (PCR) to identify H-RS cells with clonal Ig gene rearrangements in biopsy specimens of patients with relapsed HD. The obtained clonal variable region heavy-chain (VH) gene rearrangements were used to construct tumor-clone-specific oligonucleotides spanning the complementarity determining region (CDR) III and somatically mutated areas in the rearranged VH gene. A number of biopsies were obtained during a period of 3 years from two HD patients. H-RS cells with identical VH rearrangements were detected in two separate infiltrated lymph nodes from one patient with nodular sclerosis HD. In a second patient with mixed cellularity HD subtype, clonal VH rearrangements with identical sequences were detected in infiltrated spleen and two lymph node biopsies. Despite the high sensitivity of the PCR method used (one clonal cell in 10(5) mononuclear cells), residual H-RS cells were not found in peripheral blood, leukapheresis material, purified CD34(+) stem cells or bone marrow. The results show that different specimens from relapsed patients suffering from classical HD carry the same clonotypic IgH rearrangements with identical somatic mutations, demonstrating the persistence and the dissemination of a clonal tumor cell population. Thus, PCR assays with CDRIII-specific probes derived from clonal H-RS cells are of clinical importance in monitoring the dissemination of HD and tumor progression and could be useful for analysis of minimal residual disease after autologous stem cell transplantation.
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PMID:Detection of clonal Hodgkin and Reed-Sternberg cells with identical somatically mutated and rearranged VH genes in different biopsies in relapsed Hodgkin's disease. 976 76

Cure is warranted in most cases of localized Hodgkin's disease, the more frequent ones. However, after 10 years of follow-up, early and late mortality of iatrogenic origin exceed casualties related to tumor progression. Reductions in irradiation doses and fields, as well as wiser chemotherapy choices attempt to circumvent these complications. Nevertheless, as long as the mechanism of disease propagation and the prognostic factors are not better defined, only pragmatic approaches are being tested. Large cooperative trials are therefore needed to improve the outcome.
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PMID:[Prognostic factors and treatment of localized Hodgkin's disease]. 978 Nov 51

The expression of the cell death-inducing protein, Bak, was investigated in 41 cases of Hodgkin's disease and was correlated with Epstein-Barr virus (EBV) status. Overall, Bak immunostaining was observed in 35/41 cases (85%). Among the 22 EBV-positive cases, 20 cases (91%) expressed Bak while 15/19 EBV-negative cases (79%) contained Bak-positive Reed-Sternberg cells. The expression of Bak, as assessed by the staining intensity and the numbers of positive tumor cells, varied greatly from case to case but was high in 6 cases (15%). Our findings show that, similar to Bax, a second apoptosis-inducing gene Bak is frequently expressed in Hodgkin's disease. Whilst Bak is suspected to protect cells immortalized by EBV from apoptosis, its expression in Hodgkin's disease appears to be unrelated to the EBV status of Reed-Sternberg cells. Moreover, the potential pro-apoptotic functions related to Bak and Bax in Hodgkin's disease might be surpassed by a stronger expression of anti-apoptotic molecules thus explaining tumor progression.
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PMID:Detection of the cell death-inducing protein BAK in Reed-Sternberg cells of Hodgkin's disease. 1049 82

We describe here the first well-characterized case of "composite" lymphoma of the spleen in which the two components were a low-grade and a high-grade B-cell non-Hodgkin's lymphomas. The patient was an elderly man with prominent splenomegaly and multiple hypoechogenic lesions of the spleen. A splenectomy was performed, and the macroscopic and histological findings showed the simultaneous presence of a "low-grade" B-cell lymphoma, lymphoplasmacytoid (immunocytoma) and a "high-grade" B-cell lymphoma (immunoblastic), which were spatially separated. The two lesions expressed the same immunoglobulin light chain (lambda), but the Southern blot analysis showed different patterns of immunoglobulin heavy chain (IgH) clonal rearrangement. PCR analysis followed by direct sequencing of the IgH-amplified rearrangement products provided molecular-genetic evidence that the two components of the composite lymphoma had the same clonal origin. Since both EBV LMP-1 and p53 were negative by immunohistochemistry, it is unlikely that EBV and p53 were involved in the neoplastic progression in this case. PCR analysis and direct sequencing of IgH-amplified rearrangement products are useful tools to investigate clonality in cases in which Southern blot analysis cannot be performed or does not provide conclusive findings.
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PMID:"Composite" lymphoma, lymphoplasmacytoid and diffuse large B-cell lymphoma of the spleen: molecular-genetic evidence of a common clonal origin. 1052 9

Comparative genomic hybridization (CGH) was used to detect chromosomal imbalances in tumor DNA from two relapsed samples obtained in stages II and IV of a T-cell non-Hodgkin lymphoma in order to identify genetic mechanisms involved in tumor progression of this neoplasm. With conventional cytogenetic techniques (CCT), a complex hyperdiploid karyotype was obtained in stage IV. Using CGH analysis, a normal profile was observed in stage II, whereas gains of 6p11.2, 7q11.2, 7q21-->q32, 7q34, 10p13, Xp11.4, and loss of 4q33-->qter chromosomal regions were detected in stage IV.
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PMID:Identification by comparative genomic hybridization of genetic changes involved in tumoral progression of a T-cell non-Hodgkin lymphoma. 1070 Aug 65

Angiogenesis entails new vessel formation from preexisting vessels. It follows vasculogenesis during embryo development. In post-natal life, it occurs both in physiological conditions (wound repair and cyclically in the female genital system) and pathological conditions such as tumors. Several sequential steps are involved, including basement membrane degradation by proteolytic enzymes secreted by the endothelial cells, chemotaxis toward the stimulus and proliferation of these cells, canalization, branching and formation of vascular loops, stabilization and functional maturation of neovessels following perivascular apposition of pericytes and smooth muscle cells, and neosynthesis of basement membrane constituents. Tumor angiogenesis is regulated by several factors, mainly growth factors for the endothelial cells secreted by both the tumor and host inflammatory cells, and mobilized from extracellular matrix stores by proteases secreted by tumor cells. Regulatory factors also include the extracellular matrix components and endothelial cell integrins, hypoxia, oncogenes and tumor suppressor genes. Angiogenesis is mandatory to the process of tumor progression (growth, invasion and metastasis), since it conveys oxygen and metabolites, whereas endothelial cells secrete growth factors for tumor cells and a variety of proteinases which facilitate invasion and increase opportunities for tumor cells to enter the circulation. We present our results concerning the relationship between angiogenesis and progression in patients with melanoma, multiple myeloma, B-cell non-Hodgkin's lymphomas and mycosis fungoides. Lastly, it is becoming increasingly evident that agents interfering with blood vessel formation also interfere with tumor progression. These include antagonists of angiogenic growth factors, angiogenic receptors, endothelial cell integrins, and proteolytic enzymes, as well as non-specific toxic agents for vessels and low-dose chemotherapeutic agents. Their recent applications in preclinical models and in neoplastic patients are reviewed.
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PMID:[Angiogenesis and anti-angiogenesis in human neoplasms. Recent developments and the therapeutic prospects]. 1084 87

Non-Hodgkin's lymphomas (NHLs) are a group of clinically important neoplasms with a complex biology that makes their classification and treatment difficult. Their incidence is increasing and they cause significant morbidity and mortality. NHLs result from transformation of B and T/natural killer (NK) cells. Their genetic hallmark is chromosomal translocations resulting from aberrant rearrangements of IG and TCR genes, which lead to inappropriate expression of genes at reciprocal breakpoints that regulate a variety of cellular functions, including gene transcription, cell cycle, apoptosis, and tumor progression. Cytogenetics followed by molecular genetic analysis of some of the recurring translocations continues to provide new insights into lymphomagenesis and cell biology. More recently, chromosomal and gene amplification and gene deletion have been recognized as frequent genetic changes that may play a role in lymphoma progression and clinical behavior. In this review, cytogenetic data pertaining to recurring chromosomal changes on lymphomas are reviewed and examined in relation to their relevance to lymphoma development, classification, and clinical behavior.
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PMID:Recurring chromosomal abnormalities in non-Hodgkin's lymphoma: biologic and clinical significance. 1107 61

The end-results of extended radical radiotherapy for stage II-III Hodgkin's disease with apparent factors of risk of relapse in the lung and/or liver are presented. The procedure included prophylactic irradiation of both organs. Ten-year relapse-free survival in the lung-irradiation group was 85.9%, overall 10-year survival--94.0%; the liver-irradiation group--90.0 and 94.7%, respectively. Preventive irradiation was shown to significantly decrease the influence of such risks as extended lesions of the mediastinum and spleen. Relapse in the lung was recorded in one case (1.6%) only, with no tumor progression defected in the liver. Significant increase in 5- and 10-year relapse-free survival was established in the lung-irradiation group, as a result of a comparison of the study group and that of controls who showed characteristic signs of intrathoracic risk. Significant difference in overall survival was recorded for the first three years only. As far as the liver-irradiation factor is concerned, the rise in both categories of survival was significant for the 10 years. It is suggested that patients with stage II-III Hodgkin's disease receive prophylactic irradiation whenever they reveal significant signs of risk of relapse in the lung and/or liver.
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PMID:[Experience with and perspectives of an extended radical regimen of radiotherapy for Hodgkin's disease with prophylactic irradiation of the liver and the lungs]. 1121 46


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