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)

T cells infiltrating (T-TIL) B cell non-Hodgkin's lymphomas (NHL) are thought to represent a local host response to the tumor. However, tumor progression in the presence of this T cell infiltrate suggests that the T-TIL may be functionally impaired. To address this issue we determined whether response to stimulation of T-TIL from 25 patients with NHL through the T cell receptor (TCR/CD3) and the interleukin-2 (IL-2) receptor (IL-2R) was intact, since activation of these receptors is important for proliferation and cytokine production. Our results demonstrate defects in response to stimulation via TCR/CD3 and the IL-2R in T-TIL cells from patients with NHL that were not observed with T cells from the peripheral blood. T-TIL showed minimal proliferation to anti-CD3 and only modest proliferation to IL-2 alone or when combined with anti-CD3. Moreover, cytokine production in T-TIL was impaired since stimulation through the TCR/CD3 complex did not induce mRNA for interferon gamma (IFN gamma), IL-2, IL-4 or IL-10. The functional unresponsiveness of these cells may be linked to altered signalling through the TCR/CD3 since an abnormal tyrosine phosphorylation pattern was detected in T-TIL after stimulation with anti-CD3.
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PMID:Responses to T cell receptor/CD3 and interleukin-2 receptor stimulation are altered in T cells from B cell non-Hodgkin's lymphomas. 755 87

Expression of isoforms of the CD44 is generated by alternative splicing of CD44 gene; CD44H: lacks all 10 alternative exons, CD44R: the alternative exons v8 to v10, CD44V: other group of variants which contains the alternative exon v6. In some tumors such as colorectal cancer, breast cancer, non-Hodgkin lymphoma, and melanoma, over-expressed CD44 isoform which contains such alternative-spliced variant exons may play a causative role in tumor metastasis. In lung cancer, however, the role of CD44 variants in tumor progression and metastasis is uncertain. In our study and reported literature, no definite correlation was observed between the expression of specific CD44 isoform and tumor progression or metastasis of lung cancer.
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PMID:[Expression of CD44 alternative splicing variants in lung cancer]. 763 11

Cytogenetic analysis of Non-Hodgkin's Lymphomas (NHL) taken together with immunophenotypic and genotypic studies, may contribute to better define their morphologic classification. In this review the main cytogenetic data have been summarized, looking at a histopathologic NHL categorization that is related to a modern multiparametric approach. The correlation of non random chromosome abnormalities with NHL categories will augment information about their pathogenesis and tumor progression.
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PMID:[Cytogenetic analysis in the definition and classification of non-Hodgkin's lymphomas]. 770 33

The LAZ3 gene encodes a novel zinc-finger protein that shares homology with several Drosophila transcription factors. This gene was identified by its disruption in translocations involving chromosome 3q27 in diffuse large-cell lymphomas. To assess the frequency and role of this gene's involvement in lymphomagenesis and tumor progression, we examined a series of 170 cases of non-Hodgkin's lymphomas of B-cell lineage for LAZ3 gene rearrangement, expression, and mutation. The cases included 35 de novo diffuse aggressive lymphomas (DAL; 19 large-cell, 4 mixed-cell, and 12 large-cell immunoblastic), 52 transformed aggressive lymphomas derived from follicular lymphomas (TFL), 42 indolent follicular lymphomas (FL), 14 mantle cell lymphomas (MCL), and 27 small noncleaved cell lymphomas (SNCL). LAZ3 rearrangements were found in 10 DAL (28.6%), 9 TFL (17.3%), and 6 FL (14.3%), but not in any of the SNCL or MCL. LAZ3 rearrangement was not exclusive of bcl-2 rearrangement. Most rearrangement breakpoints mapped to a 10-kb BamHI-Xba I fragment located 5' to the LAZ3 coding sequence, consistent with previously reported breakpoint locations. Northern analysis of both rearranged and nonrearranged B-cell lymphoma cases showed similar levels of a transcript of approximately 3.8 kb, indicating that LAZ3 is broadly expressed in B-cell tumors and is not confined to rearranged cases. To investigate whether mutation of the LAZ3 gene might contribute to a potential role for this gene in lymphomagenesis, we screened the coding sequences of 13 rearranged cases, 6 nonrearranged cases, and 13 hematopoietic tumor cell lines. Although three probable polymorphisms were identified, mutations were detected in only 2 rearranged cases. Only 1 of these resulted in an amino acid substitution. Two cell lines (SU-DHL4 and Molt-4) also contained mutations; only one resulted in an amino acid substitution. We conclude (1) that LAZ3 rearrangements occur in a significant fraction of de novo DAL as well as in a smaller subset of indolent and transformed follicular lymphomas; (2) that LAZ3 message is expressed in both rearranged and nonrearranged B-cell lymphomas; and (3) that mutation of the LAZ3 gene does not contribute to its putative oncogenic role in most 3q27 translocated B-cell lymphomas.
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PMID:Analysis of LAZ3 (BCL-6) status in B-cell non-Hodgkin's lymphomas: results of rearrangement and gene expression studies and a mutational analysis of coding region sequences. 774 50

Interactions between cancer cells and laminin, a major component of basement membranes, are mediated through a large variety of cell surface proteins designated as laminin receptors. Among the above proteins, a 67-kd monomeric high affinity laminin receptor (67 LR) has long been suspected to be involved in tumor progression. In this study we wished to establish whether the 67 LR molecule is detectable on tumor cells of Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHLs), to define its pattern of expression, and to assess the potential utility of 67 LR in differentiating these pathological entities. Morphological and immunohistological studies were performed on 85 specimens of HD and a series of 334 NHL specimens, including anaplastic large cell (ALC) (CD30-positive) lymphomas (73 specimens). For immunohistochemical assessment of the 67 LR we used the monoclonal antibody (MoAb) MLuC5 directed against the 67-kd laminin receptor on paraffin-embedded sections. Reed-Sternberg cells reacted with MLuC5 MoAb in four of 85 (4.7%) HD specimens. Among the NHL specimens, a MLuC5-positive reaction was expressed in 3.3% of B-cell lymphomas. They all belonged to the high grade subtypes. On the other hand, a MLuC5-positive reaction was detected in none of the T-cell lymphomas tested. In contrast to the results obtained with the other NHLs, in 30.2% of ALC (CD30-positive) lymphoma specimens, tumor cells reacted with MLuC5 MoAb. MLuC5-expressing ALC (CD30-positive) lymphoma cells were of either T-cell (six of 17 specimens), B-cell (three of 25 specimens), or undetermined phenotype (10 of 31 specimens). Our investigation has shown that 67 LR as shown by MLuC5 MoAb is detectable only in neoplastic cells of a fraction of ALC (CD30-positive) lymphomas and small subsets of B-cell high grade NHLs and HD. The restricted expression of the 67 LR molecule to ALC (CD30-positive) lymphomas provides a potential tool for the phenotypic separation of this pathological entity from HD and other lymphomas. Whether the detection of the 67 LR expression in these lymphoma subsets may be related to the aggressiveness of the disease remains to be ascertained.
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PMID:Expression of the monomeric 67-kd laminin-binding protein in human lymphomas as defined by MLuC5 monoclonal antibody and paraffin section immunohistochemistry. 1008 60

Invasive thymoma recently has been shown to be sensitive to combination chemotherapy and in some cases to be relatively indolent. Two cases of extensive thymoma which responded to primary treatment with a combination of a platinum compound (carboplatin or cisplatin), doxorubicin (Adriamycin), and cyclophosphamide (or PAC) are described. Tumor progression occurred 14 (case 1) and 60 months (case 2) after completion of initial PAC therapy and was treated with the same regimen resulting in a second remission, which lasted 6 months in case 1 and is continuing at 8 months in case 2. Similar reports of secondary responses using the same chemotherapy have been described in breast, lung, and ovarian cancers, as well as in Hodgkin's lymphomas. Our observations suggest that retreatment with the same platinum-based regimen should be considered in patients who have progressive thymomas following a previous chemotherapeutic response and a disease-free interval of greater than 12 months.
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PMID:Retreatment of recurrent invasive thymoma with platinum, doxorubicin, and cyclophosphamide. 926 13

A feasibility study was carried out on the treatment for refractory and relapsed non-Hodgkin's lymphomas with a combination of two oral topoisomerase II inhibitors, MST-16 and VP-16. On the basis of the synergistic activity in preclinical studies and the schedule dependency in these drugs, low-dose and long-term administration was planned. For the anticipated myelosuppression, two different regimens were designed as an open label trial in this study. In Regimen I, 400 mg of MST-16 combined with 25 mg of VP-16 was administered daily. With this regimen, the response rate (RR)/median time to tumor progression (TTP) in all evaluable patients was 50% (2/4)8.5 months in low grade (indolent) lymphoma and 60% (6/10)/5.2 months in intermediate/high grade (aggressive) lymphomas. In Regimen II, 400 mg of MST-16 combined with 25 mg of VP-16 was administered intermittently (3 days a week or every other day). With this regimen, there was an RR/median TTP of 60% (3/5)/7.0 months in indolent lymphoma and 33.3% (4/12)/1.1 months in aggressive lymphoma. A major side effect in both of these regimens was myelosuppression, with the incidence of grades 3 and 4 toxicity being higher in Regimen I than in Regimen II. The other side effects were uncommon and not severe. These findings indicated that two regimens were tolerated well and were promising for refractory and relapsed aggressive non-Hodgkin's lymphomas. To define the anti-tumor activity and safety of these regimens precisely, large-scale prospective randomized trials are necessary.
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PMID:Feasibility of salvage chemotherapy for refractory or relapsed non-Hodgkin's lymphoma with two topoisomerase II inhibitors, MST-16 and VP-16. MST-16 Study Group. 892 84

In a variety of human tumors, including high grade Non-Hodgkin's lymphoma (hgNHL), a linkage between expression of CD44 variant isoforms (CD44v) and tumor progression has been described. In search of an easily accessible diagnostic parameter, expression of CD44 standard (CD44s) and CD44 variant isoforms (exons v5, v6, v7 and v10) in peripheral blood lymphocytes (PBLs) of patients with hematological malignancies was evaluated by fluorescence activated cell scanning. The analysis of 30 blood samples of healthy donors and patients with non-malignant diseases and of 183 blood samples of patients with malignant hematological disorders revealed that only in patients with malignant disorders did a measurable proportion of PBLs express CD44 variant isoforms, mostly exons v5, v6, v7 and, less frequently, exon v10. Elevated levels of CD44v expression were noted in PBLs of patients with acute and chronic myeloid leukemia (AML: 16%, CML: 25%), Hodgkin's disease (HD: 17%), multiple myeloma (MM: 22%), polycythemia vera (PV: 33%), acute lymphoid leukemia (ALL: 23%) and, most frequently, in PBLs of patients with non-Hodgkin's lymphoma (NHL:54%). CD44v expression was not restricted to the malignant phenotype, but instead was also noted in T cells, B cells and monocytes, preferentially in a subpopulation of large cells. Furthermore, expression of CD44v in PBLs was not linked to the histological grading or clinical staging. There was, however, an inverse correlation with tumor progression, whereas response to therapy was frequently accompanied by upregulation of CD44v. Thus, expression of CD44v in the PBLs of patients with NHL mainly reflected immune responsiveness. Since NHL manifests itself primarily in lymphoid organs, its progression is difficult to follow. Monitoring of CD44v in PBLs could be used as an additional and convenient parameter for surveying the course of disease.
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PMID:Expression of CD44 variant isoforms in peripheral blood leukocytes in malignant lymphoma and leukemia: inverse correlation between expression and tumor progression. 896 Jan 9

DNA methylation has been studied intensively during the past years in order to elucidate its role in the regulation of gene expression, gene imprinting and cancer progression. Earlier studies have shown that a general genomic under-methylation is associated with chronic lymphocytic leukemia and metastatic prostate cancer. Site-specific methylation changes, as revealed by the use of methylation-sensitive restriction enzymes, have been reported to occur in the promotor region of the calcitonin gene in chronic myeloid leukemia as it progresses from the chronic phase to blast crisis, in non-Hodgkin's lymphoid neoplasms and in non-lymphocytic leukemia. We have now explored possible methylation changes associated with benign and malignant breast tumors. Two approaches were employed: (i) chemical determination of general genomic methylation status and (ii) base-specific analysis of the methylation changes in the promoter of the calcitonin gene with the aid of genomic sequencing. The results did not reveal any changes of total DNA 5-methylcytosine content in ductal carcinoma of breast in comparison with benign tumors. There was a small, yet significant, increase in 5-methylcytosine content in lobular carcinoma. Genomic sequencing of the promoter region of the calcitonin gene, however, revealed a striking hypermethylation at or around the transcription start site of the gene in ductal carcinomas. In benign tumors and lobular carcinomas, this region was either entirely unmethylated or only slightly methylated. The latter changes may reflect a regional hypermethylation of the short arm of chromosome 11, which harbors, in addition to the calcitonin gene, a number of putative or established tumor-suppressor genes. Our results demonstrate that genomic sequencing in its present form can be used for a reliable and precise DNA methylation analysis of primary human tumors.
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PMID:Hypermethylation of calcitonin gene regulatory sequences in human breast cancer as revealed by genomic sequencing. 898 Feb 49

Mantle-cell lymphoma comprises 2%-10% of all non-Hodgkin's lymphomas (NHLs). Patients present with generalized disease, and have a poor prognosis. Three different histologic patterns (mantle zone, nodular, and diffuse) and three different cytological variants (classical, blastic, and pleomorphic) have been described. The phenotype (strong surface IgM, CD5+, CD10-, CD23-, cyclin D1+ and B-cell markers+) is remarkably constant. Dependent on the methods used (PCR, Southern blot analysis, and cytogenetics) a t(11;14) can be detected in approximately 35%-66% of cases. Using FISH analysis, possibly almost all cyclin D1-expressing MCLs carry this translocation, indicating that a substantial part of these translocations are missed by conventional methods. This has been confirmed by DNA fiber FISH analysis by which the breakpoints could be accurately mapped over a 220 kb region centromeric of the cyclin D1 gene. Additional genetic abnormalities involve breakpoints and deletion at the 3' end of the cyclin D1 gene, numerical chromosomal aberrations, mutations in p53, and deletions of p16. These may be associated with tumor progression. Owing to the translocation t(11;14), the cyclin D1 gene is activated. At the RNA level, approximately 90% of MCLs show overexpression. This corroborates immunohistochemistry on paraffin tissue sections. Since expression of cyclin D1 in normal lymphoid cells is very low to undetectable, and only hairy-cell leukemia and very few other B-cell lymphomas show expression, immunohistochemistry for cyclin D1 provides an excellent marker for MCL. In hairy-cell leukemia, expression is moderate and cannot be explained by chromosomal translocation.
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PMID:Bcl-1/cyclin D1 in malignant lymphoma. 920 53


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