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)

Activated lymphocytes and malignant lymphoma cells derived from them (Ki-1 positive lymphoma cells) share similar mechanisms of proliferation. To further examine the inhibitory role of endogenous transforming growth factor beta (TGF beta) in Ki-1 positive lymphoma cells, the authors studied anti-TGF beta antibodies and measured their effect on proliferation. A monoclonal antibody (T1A5) prepared against a unique antigenic epitope of high molecular weight Hodgkin's TGF beta and a polyclonal rabbit antibody prepared against highly purified 25,000 D porcine platelet TGF beta 1 were used. Both antibodies are shown here to inhibit the biological activity of Hodgkin's TGF beta and to crossreact with their respective antigens in immunoblotting. DNA synthesis by Ki-1 lymphoma cells was increased 138-fold by anti-TGF beta 1 antibody and 262-fold by anti-Hodgkin's TGF beta. Exogenous TGF beta 1 suppression was completely reversed by anti-TGF beta 1 antibody and IL-2-induced proliferation was markedly potentiated (41 fold). L-428 Reed-Sternberg cells secrete physiologically active TGF beta but have fewer than 500 TGF beta receptor sites per cell; no significant proliferative response was measured for either anti-TGF beta 1 or anti-Hodgkin's TGF beta. These results show the suppressive effect of exogenous TGF beta 1 on indolent Ki-1 lymphoma cells and suggest that the endogenous secretion of high molecular weight physiologically active TGF beta is important in maintaining the indolent nature of this low-grade Ki-1 positive lymphoma.
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PMID:Neutralizing antibodies against transforming growth factor beta potentiate the proliferation of Ki-1 positive lymphoma cells. Further evidence for negative autocrine regulation by transforming growth factor beta. 131 8

To measure the in vivo secretion of high molecular weight (HMW) transforming growth factor (TGF)beta by Reed-Sternberg cells from patients with nodular sclerosing Hodgkin's disease, we studied the urine samples from untreated patients. The urinary proteins did not promote the proliferation of NIH-3T3 cells in monolayer culture and contained similar amounts of total TGF activity when compared with normal controls. Urinary proteins from 24 different control and test urines were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Either of two primary antibodies were used for immunoblot detection: (a) affinity column purified polyclonal anti-TGF beta 1 prepared against platelet TGF beta 1 or (b) monoclonal anti-HMW-TGF beta prepared against HMW-TGF beta secreted by cloned L-428 Reed-Sternberg cells. All patients with active nodular sclerosing Hodgkin's disease had a detectable HMW-TGF beta (approximately 300,000) which cross-reacted with both anti-TGF beta 1 and anti-HMW-TGF beta. Purification demonstrated HMW-TGF beta which was active at physiological pH. Twelve control urine samples from healthy adults and 5 follow-up samples from the Hodgkin's patients after successful treatment contained no detectable urinary HMW-TGF beta. The in vivo production of HMW-TGF beta in untreated nodular sclerosing Hodgkin's disease supports the conclusion that this growth factor is secreted in large amounts by Reed-Sternberg cells or cells stimulated by Reed-Sternberg cells.
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PMID:High molecular weight transforming growth factor beta is excreted in the urine in active nodular sclerosing Hodgkin's disease. 145 64

The loss of bands p21-22 from one chromosome 9 homologue as a consequence of a deletion of the short arm [del(9p)], unbalanced translocation, or monosomy 9 is frequently observed in the malignant cells of patients with lymphoid neoplasias, including acute lymphoblastic leukemia and non-Hodgkin lymphoma. The alpha- and beta 1-interferon genes have been assigned to this chromosome region (9p21-22). We now present evidence of the homozygous deletion of the interferon genes in neoplastic hematopoietic cell lines and primary leukemia cells in the presence or absence of chromosomal deletions that are detectable at the level of the light microscope. In these cell lines, the deletion of the interferon genes is accompanied by a deficiency of 5'-methylthioadenosine phosphorylase (EC 2.4.2.28), an enzyme of purine metabolism. These homozygous deletions may be associated with the loss of a tumor-suppressor gene that is involved in the development of these neoplasias. The relevant genes may be either the interferon genes themselves or a gene that has a tumor-suppressor function and is closely linked to them.
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PMID:Homozygous deletion of the alpha- and beta 1-interferon genes in human leukemia and derived cell lines. 313 58

Immunoelectrophoretic study of serum proteins in patients with various types of malignant proliferations of haemopoietic tissue was performed. It was established that myeloproliferative diseases (chronic myeloleukemia, acute leukemia) are notable for changes in alpha 2-globulins (frequent increase in the content of alpha 2-macroglobulin, haptoglobin) increase in the of beta 1 A-globulin as well as for reactive increase in the content of one or several immunoglobulins. During malignant proliferations of lymphoreticular tissue (chronic lympholeukemia, lymphosarcoma, myeloma, lymphogranulomatosis), major disturbances occur in the group of immunoglobulins, changes in which during this pathology can be of three types: reactive increase, decrease with a syndrome of antibody deficiency, paraproteinemia. The type of changes of immunoglobulins is determined by morphogenetic species of malignant cells.
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PMID:[Immunoelectrophoretic characterization of the changes in serum proteins in hemoblastosis]. 531 20

Low- and high-grade malignant non-Hodgkin's lymphomas have been investigated by immunohistochemistry for their expression of various integrins and CD44 isoforms. Comparison with the expression patterns obtained in non-malignant adult lymph nodes revealed the following differences: alpha 6 and beta 4 integrins were expressed in several high-grade malignant lymphomas to a lower degree than in both the low-grade malignant lymphomas and the normal lymph nodes; all other integrins (alpha 2, alpha 4, alpha 5, alpha v, beta 1, beta 2, beta 3, and beta 7) did not exhibit significant differences in the expression levels between malignant and non-malignant tissues. The standard isoform of CD44 (CD44s) was highly expressed in all lymphoid tissues. Using CD44 exons-specific monoclonal antibodies, CD44 variant isoforms were not detected in non-malignant lymph nodes and were detected only rarely in low-grade malignant lymphomas. In contrast, high-grade malignant lymphomas expressed several CD44 variant isoforms, which included the products from the variant exons 3v, 6v, and 9v, but not 4v. Specifically, detection of exon 3v and 6v products indicates a more aggressive phenotype.
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PMID:Expression of integrins and CD44 isoforms in non-Hodgkin's lymphomas: CD44 variant isoforms are preferentially expressed in high-grade malignant lymphomas. 752 12

In this study the distribution patterns of various extracellular matrix components and their receptors (i.e. beta 1 integrins) in B-cell non-Hodgkin lymphomas were examined and compared to those in reactive lymphoid tissue. Neoplastic follicles within follicular lymphomas showed similar patterns to that observed in reactive follicles, which appeared to be strongly associated with the presence of follicular dendritic cells. Diffuse lymphomas of low and intermediate malignancy grade revealed features comparable to those of interfollicular areas of reactive lymphoid tissue, irrespective to which compartment the tumour cells were related. Highly malignant lymphomas, however, displayed unique extracellular matrix configurations, resulting from active matrix degradation by macrophages; this may support rapid tumour growth. Extranodal lymphomas showed virtually the same matrix patterns as their nodal counterparts, suggesting that (malignant) lymphoid cells generate (at least partly) their own specific microenvironment. In reactive lymphoid tissue beta 1 integrins were mainly found on resident cells and except for alpha 4, alpha 5 (and beta 1) the lymphoid cells expressed very little, if any, beta 1 integrins. In comparison, expression of these integrins on lymphoma cells was reduced (follicular lymphomas) or could not be detected at all (diffusely growing lymphomas); this might contribute to the growth pattern and metastatic properties of the tumours.
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PMID:Distribution of extracellular matrix components and their receptors in human lymphoid tissue and B-cell non-Hodgkin lymphomas. 753 15

The use of molecular methods to diagnose malignant lymphoma, while firmly established in reference centers, has not been well evaluated at the community level. A group of 57 specimens from patients with non-Hodgkin's lymphomas (NHL), lymphoid leukemias (LL), and a variety of other lymphoproliferative lesions with the Southern blot methodology have been studied by us. Molecular probes to the joining regions of the heavy (JH) and light (J kappa) immunoglobulin chains and the beta (J beta 1-2) chain of the T cell receptor genes were used. Gene rearrangements were detected in 90 percent of all NHL/LL with a 95 percent detection rate specifically for B-NHL/LL. In comparison, phenotypic analysis by immunoperoxidase stains favored a B phenotype in 75 percent of those cases, while flow cytometry assigned 63 percent of cases to a B cell lineage. Gene rearrangements were detected in four of six cases of T-NHL for a rate of 67 percent. The six other lymphoproliferative lesions included Hodgkin's disease, Castleman's disease, and a case of lymphoid hyperplasia. No rearrangements were detected in these specimens. The studies allowed development of increased confidence in the diagnosis of NHL/LL on ever smaller specimens. The availability of these studies has also helped establish a priority of handling all specimens so that the most appropriate studies can be performed to yield the most useful diagnostic information.
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PMID:Gene rearrangements in malignant lymphomas. 804 94

Since TGF beta 1 inhibits the proliferation of normal B-cells, its disturbed activity in B cell lymphomas is conceivable. We found high expression of TGF beta 1 mRNA in three human B cell non-Hodgkin lymphoma xenografts; also, the gene product (in latent form) was detectable in all lymphoma cells. However, on exposing the cells to exogenously activated TGF beta 1, the incorporation of tritiated thymidine decreased in normal (murine thymocytes, human peripheral mononuclear cells), but not in lymphoma cells. These observations suggest the malfunction of TGF beta 1 mediated regulatory pathway (e.g. insufficient activation or receptor expression) which can contribute to the unlimited expansion of a lymphoid clone. The opposite expression of c-myc to TGF beta and the retained sensitivity to anti-IgM indicate that c-myc and Ig receptor can operate independently of TGF beta in the regulation of lymphoid cell proliferation.
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PMID:Loss of transforming growth factor beta 1 regulatory activity in human non Hodgkin lymphomas. 816 37

Follicular dendritic cells are the major supporting cell of the germinal center microenvironment. The major function of follicular dendritic cells is to present antigen to B cells in secondary lymphoid tissues. Through cell-cell interactions, FDCs are hypothesized to be central to the regulation of normal B cell growth and differentiation. The major receptor-ligand pair which mediates B cell-FDC adhesion is the beta 1 integrin VLA-4, present on B cells and VCAM-1 expressed on FDCs. Follicular non-Hodgkin's lymphomas similarly employ this mechanism to bind to neoplastic germinal centers. The VCAM-1 molecule can exist as a 6 or 7 immunoglobulin domain form. The major form of VCAM-1 on activated endothelium is the 7 domain form. In this report we have determined by polymerase chain reaction of purified FDCs that they express predominantly mRNA for 7 domain VCAM-1. It is likely that the two forms of VCAM-1 are associated with distinct functions, therefore the expression of 7 domain VCAM-1 may be important in normal and neoplastic B cell-FDC interactions.
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PMID:Expression of vascular cell adhesion molecule-1 by follicular dendritic cells. 853 91

Hepatocyte growth factor (HGF)/scatter factor (SF) is the ligand for a tyrosine kinase cell surface receptor encoded by the MET protooncogene (c-MET). HGF/SF can induce proliferation and motility in epithelial cells and promotes invasion of carcinoma cells and NIH3T3 fibroblasts transfected with both HGF/SF and c-MET genes. Our results show that HGF/ SF and c-MET also play a role in adhesion and invasion of human lymphoma cells. c-MET mRNA is expressed in hemopoietic cells, such as hemopoietic progenitor cells (CD34+ cells) in bone marrow (BM) and mobilized peripheral blood, immature B cells in cord blood and BM, and germinal center B-centroblasts. In normal peripheral blood B cells, which are c-MET-, c-MET expression was induced by PMA, ConA, HGF/ SF, and Epstein-Barr virus (EBV) infection. Using immunohistochemistry, we detected c-MET on the cell surface of large activated centroblasts in lymph nodes from patients with B-non-Hodgkin's lymphoma and Hodgkin's disease. In the latter group, c-MET expression correlated well with the presence of EBV. Because HGF/SF and c-MET promote metastasis of carcinoma cells, we studied the effects of c-MET stimulation by HGF/SF of B-lymphoma cells on properties relevant for metastasis, ie, adhesion, migration, and invasion. HGF/SF stimulated adhesion of the c-MET+ B-cell lines to the extracellular matrix molecules fibronectin (FN) and collagen (CN) in a dose dependent manner. However, adhesion to laminin was not affected by HGF/SF. Adhesion to FN was mediated by beta 1-integrins alpha 4 beta 1 (VLA4) and alpha 5 beta 1 (VLA5) since blocking antibodies against beta 1- (CD29), alpha 4-(CD49d), or alpha 5- (CD49e) integrin subunits, completely reversed the effect of HGF/SF. Furthermore, HGF/SF induced adhesion was abrogated by addition of genistein, which blocks protein tyrosine kinases, including c-MET. Addition of HGF/SF resulted in a sixfold increase in migration of c-MET B-lymphoma cells through Matrigel, compared to medium alone. In rat fibroblast cultures, HGF/SF doubled the number of c-MET+ B-lymphoma cells that invaded the fibroblast monolayer. In these adhesion, migration and invasion assays HGF/SF had no effect on c-MET- cell lines. In conclusion, c-MET is expressed or can be induced on immature, activated, and certain malignant B cells. HGF/SF increased adhesion of c-MET+ B-lymphoma cells to FN and CN, mediated via beta 1-integrins alpha 4 beta 1 and alpha 5 beta 1, and furthermore promoted migration and invasion.
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PMID:Hepatocyte growth factor/scatter factor promotes adhesion of lymphoma cells to extracellular matrix molecules via alpha 4 beta 1 and alpha 5 beta 1 integrins. 902 31


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