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

The clonality of Reed-Sternberg cells is still a matter of controversy. In Hodgkin's disease, these cells rarely constitute more than 2% of all cells in tissue biopsies of lymph node lesions, the rest being a large collection of various reactive cells. To determine in which cells the abnormal karyotype occurs, we studied two patients with Hodgkin's disease by a cytogenetic method allowing simultaneous analysis of cell morphology, immunologic phenotype, and karyotype in the same mitotic cell. The Ber-H2 (CD30) and Leu-M1 (CD15) monoclonal antibodies were used to identify mitotic Reed-Sternberg cells. In 24-48-hour cultures of lymph node cells from Hodgkin's lesions, there was a mixture of cells with an abnormal clonal karyotype and a normal karyotype. The abnormal clonal karyotype was restricted to Ber-H2- and Leu-M1-positive cells, i.e., the Reed-Sternberg cells. In keeping with these findings, most of the clonal atypical karyotypes occurred in kappa- and lambda-positive large cells, i.e., Reed-Sternberg cells. Mitotic cells with T markers (CD3,4,8) or B markers (CD22) had the normal karyotype. There were no mitoses in cells expressing the antigens recognized by Leu11 (CD16) or Leu11 + Leu7. These findings provide strong evidence suggesting that in Hodgkin's disease only the Reed-Sternberg cells possess a clonal karyotypic abnormality and thus are most probably the only neoplastic component in Hodgkin's disease.
 ...
PMID:Unique display of a pathologic karyotype in Hodgkin's disease by Reed-Sternberg cells. 340 2

This paper describes a newly recognized clinicopathologic syndrome of regressing cutaneous nodules, peripheral lymphadenopathy and fever occurring mainly in children and adolescents. Skin lesions show pseudoepitheliomatous hyperplasia, absence of epidermotropism and pleomorphic large lymphoma cells infiltrating the dermis and subcutaneous fat. Lymph nodes have a distinctive appearance with lymphoma cells in sinuses and paracortex. Despite their usual histiocyte-like appearance, the lymphoma cells in most cases have an aberrant T-cell phenotype, expressing several activation antigens including Hodgkin's disease associated antigen Ki-1 (CD30). Clonal rearrangements of the beta chain genes for the T-cell antigen receptor (TCR) were found and revealed a T-cell origin in one case lacking T-cell surface antigens. Identical rearrangements of the TCR genes indicated a monoclonal origin for separate lesions on the arm and leg of another patient. Treatment results in the first group of patients indicate that radiation treatment of an affected area is associated with frequent relapse at other sites, but multiagent chemotherapy (COMP or D-COMP) produces durable remissions in nearly all patients. Bone marrow transplantation was effective salvage therapy for treatment failures. Further studies are underway to investigate the mechanism(s) of tumor regression, the epidemiology, and etiology of Ki-1+ lymphomas which appear to be relatively more frequent in Oriental and Black patients, and in which the first lesion may resemble an insect bite.
 ...
PMID:Cutaneous Ki-1 lymphoma: pathology, immunology and clinical characteristics. 350 41

Waldeyer's ring is an uncommon, rarely reported primary site for Hodgkin's disease. We report a series of 16 such cases culled from the files of the Armed Forces Institute of Pathology and the National Cancer Institute. The patients' median age was 41 years (range, 14-74), and they presented with airway obstruction or unilateral tonsillar enlargement. The disease was localized to the Waldeyer's ring (stage I) in 46% of patients and extended to the cervical lymph nodes (stage II) in 39% and to the spleen (stage III) in 15%. Local radiation therapy, with or without chemotherapy, obtained a complete response in all but two patients. There was local recurrence in one patient and distant spread in three others. All patients for whom follow-up is available are alive without evidence of disease at 9 to 216 months (median, 20 months) except two who died of widespread Hodgkin's disease and two others who died of other causes. Histologically, eight cases were classified as mixed cellularity type (50%), four as nodular sclerosis (25%), and one as lymphocyte predominance, nodular (LPn; 6.3%); three others that showed interfollicular involvement were unclassified (18.7%). The Reed-Sternberg (RS) and atypical mononuclear cells in most cases of mixed cellularity and interfollicular types and all cases of nodular sclerosis had the classic immunophenotype (CD45-, CD20- and/or CD45RO-, CD15+ and/or CD30+). In the single case of LPn, they were of B-cell lineage (CD45+, CD20+, CD45RO-, CD15-, CD30-). In situ hybridization performed on routinely processed sections revealed Epstein-Barr virus (EBV) EBER1 mRNA in RS cells of eight of 12 cases studied (67%) only in mixed cellularity and nodular sclerosis, but not in LPn. We conclude that, however rarely, Hodgkin's disease of typical morphology and immunophenotype can originate in Waldeyer's ring. The incidence of EBV detection in the RS cells in our study is greater than that usually seen in nodal Hodgkin's disease in the United States. The greater prevalence of EBV-related Hodgkin's disease at this site is probably a reflection of the fact that the Waldeyer's ring is a reservoir for EBV.
 ...
PMID:Hodgkin's disease of Waldeyer's ring. Clinical and histoimmunophenotypic findings and association with Epstein-Barr virus in 16 cases. 750 65

Local tumor growth has been reported after subcutaneous and intraperitoneal injection of Hodgkin's disease (HD) derived cell lines into different immunodeficient mouse strains. An animal model with disseminated growth of tumor cells would be useful for studying the in vivo biology of HD cells as well as for preclinical testing of new therapeutic regimens. For this purpose the HD-derived cell lines L540, L540cy, L428, and KM-H2 were injected intravenously into SCID mice. In contrast to L428 and KM-H2, widespread neoplasia occurred after a period of four to six weeks following injection of L540 and the subline L540cy. Lymph nodes were found to be the preferred site of tumor growth. CD30 surface antigen expression on Hodgkin cells and the karyotype of the tumor cells were preserved in the animal host. Thus, to a large extent, the SCID mouse model mimics the dissemination pattern of Hodgkin's disease in man. To evaluate the role of adhesion molecule expression in the dissemination of HD-derived cell lines, CD44 and members of the immunoglobulin, integrin, selectin, and Fc receptor families were quantified by flow cytometry. CD30 expression was also measured. Although CD44 expression has been correlated with dissemination in non-Hodgkin's lymphoma (NHL), this was not the case in the Hodgkin's SCID mouse model. CD44 was not expressed on the disseminating cell lines L540 and L540cy but was expressed in the nondisseminating lines L428 and KM-H2.
 ...
PMID:Disseminated growth of Hodgkin's-derived cell lines L540 and L540cy in immune-deficient SCID mice. 751 37

Analysis of most hematologic neoplasms indicates the involvement of one or more cell lineages in the bone marrow and/or the blood but rules out the involvement of all lineages in any one neoplasm. It is important to detect lineage involvement in order to clarify which stem cells are involved in leukemia, to predict prognosis, and to select appropriate treatment. Our aim was to study the cell lineage involvement of some of the recurrent chromosomal abnormalities seen in hematological neoplasms. The direct morphology-antibody-chromosomes (MAC) method was used. The deletion 20q in myeloproliferative diseases (MPD), the deletion of 5q and t(1;7) in myelodysplastic syndromes (MDS), and t(3;3) in acute myeloid leukemia subtype M7 (AML-M7) were seen in all or at least in two myeloid lineages. These were interpreted as stem cell abnormalities. Deletion 13q in MPD, t(8;21) in AML-M2 and t(15;17) in AML-M3 were seen in granulocytic lineages only; t(14;18) in non-Hodgkin's lymphoma and trisomy 12 as the sole abnormality in chronic lymphocytic leukemia (B-CLL) were seen only in immunoglobulin light chain clonal B cells; inversion 14 in T-CLL was seen only in T cells, whereas t(15;14) in acute lymphocytic leukemia with eosinophilia (ALL-EO) was seen in lymphoid stem cells but not in mature granulocytes or lymphocytes. Additional abnormalities (in addition to the Philadelphia chromosome) in chronic myeloid leukemia (CML) were seen in all myeloid cell lineages and also in mature granulocytes, B cells, and large granular lymphocytes. Abnormalities in Hodgkin's disease were restricted to CD30-positive Reed-Sternberg cells. Trisomy 8 and monosomy 7 are abnormalities that may be present in either stem cells or any of the single cell lineages.
 ...
PMID:Cell lineage involvement of recurrent chromosomal abnormalities in hematologic neoplasms. 752 Feb 72

CD40 was originally described as a B-cell-restricted antigen and was subsequently found to be a member of the tumor necrosis factor (TNF) receptor superfamily. CD40 is also expressed on dendritic cells, thymic epithelium, monocytes, and some carcinoma cell lines, and plays a critical role in cell contact-dependent activation. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, the presumed malignant cells of Hodgkin's disease (HD); were found to express high levels of cell surface CD40. We found that recombinant CD40 ligand (CD40L) induced interleukin-8 (IL-8) secretion and enhanced IL-6, TNF, and lymphotoxin-alpha (LT-alpha/TNF-beta) release from cultured H-RS cells. These cytokines play a significant role in the clinical presentation and pathology of HD, a tumor of cytokine-producing cells. CD40L had no mitogenic activity for HD-derived cell lines. In contrast, CD40L enhanced expression of costimulatory molecules intracellular adhesion molecule-T and B7-1 on cultured H-RS cells, both of which are overexpressed on primary H-RS cells. In addition, CD40L induced a 40% to 60% reduction of the expression of the HD-associated CD30 antigen, another member of the TNF receptor superfamily. Primary and cultured H-RS cells express not only CD30, but also CD40. CD40L has pleiotropic biologic activities on H-RS cells, and the CD40-CD40L interaction might be a critical element in the deregulated cytokine network and cell contact-dependent activation cascade typical for HD.
 ...
PMID:Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the possible relevance for Hodgkin's disease. 752 24

T-cell non-Hodgkin's lymphomas can be considered the neoplastic equivalents of immunologically functional, site-restricted T lymphocytes. Little is known about the occurrence and clinical behavior of T-cell lymphomas that are the neoplastic equivalents of different functional T-cell subsets. Here, we investigated the prevalence, preferential site, immunophenotype, and clinical behavior of the neoplastic equivalents of activated cytotoxic T cells (CTLs) in a group of 140 nodal and extranodal T-cell lymphomas. Activated CTLs were shown immunohistochemically with a monoclonal antibody against granzyme B, a major constituent of the cytotoxic granules of activated T cells. Granzyme B-positive T-cell lymphomas were mainly found in mucosa-associated lymphoid tissue (MALT; nose, 63% of the cases; gastrointestinal tract, 46%; and lung, 33%). Granzyme B-positive cases with primary localization in MALT were more often associated with angioinvasion (P = .005), necrosis (P = .002), and histologic characteristics of celiac disease in adjacent mucosa not involved with lymphoma. Eosinophilia was more often observed in granzyme B-negative cases (P = .03). Most cases belonged to the pleomorphic medium- and large-cell group of the Kiel classification. CD30 expression was more often found in granzyme B-positive lymphomas of MALT (P = .04), whereas CD56 expression was exclusively found in nasal granzyme B-positive lymphomas. Immunophenotypically, most of the cases should be considered as neoplastic equivalents of activated CTLs based on the presence of T-cell markers on tumor cells. In two cases of nasal lymphoma, tumor cells probably were the neoplastic counterparts of natural killer cells. The prognosis of the granzyme B-positive gastrointestinal T-cell lymphomas was poor but did not differ from granzyme B-negative gastrointestinal T-cell lymphomas. This indicates that, in peripheral T-cell lymphomas, site of origin is more important as a prognostic parameter than derivation of activated CTLs.
 ...
PMID:Granzyme B-expressing peripheral T-cell lymphomas: neoplastic equivalents of activated cytotoxic T cells with preference for mucosa-associated lymphoid tissue localization. 752 49

Epstein-Barr virus (EBV) has been demonstrated in the Reed-Sternberg cells and their mononuclear variants (Hodgkin cells; H-RS cells) in a substantial number of Hodgkin's disease (HD) cases. Moreover, EBV can modulate both in vivo and in vitro the expression of several cellular genes, including lymphoid differentiation markers. Therefore we investigated, in 64 cases of HD, the relationship between the presence of EBV and the expression of lymphoid (CD45RB), T- (CD3, CD45RO), B- (CD20, MB2 antigen, CDw75), and myeloid-cell lineage markers (CD15), and of activation markers (CD30, EMA, and the 115D8 antigen) on the H-RS cells. EBV-positive cases, as demonstrated by the presence of EBER-1 and -2 RNA and LMP-1 protein expression, showed a significant reduction in the expression on H-RS cells of T-cell lineage (CD3, P < 0.02), B-cell lineage (CD20; P < 0.005), and activation markers (EMA; P < 0.002 and the 115D8 antigen; P < 0.001) as compared with EBV-negative cases. No differences were found in the expression of CD15, CD30, CD45RO, CD45RB, CDw75, or the MB2 antigen on H-RS cells in EBV-positive and EBV-negative HD cases. Interestingly, in 11 cases of EBV-negative HD, B- as well as T-cell lineage markers could be found on some H-RS cells. These data suggest that EBV in H-RS cells is able to down-regulate the expression of T- (CD3) and B- (CD20) cell lineage markers and lymphoid activation markers (EMA and the 115D8 antigen).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Decreased expression of cellular markers in Epstein-Barr virus-positive Hodgkin's disease. 752 10

CD30L, the ligand for the activation antigen CD30, is a member of the tumor necrosis factor family of cytokines. Binding of CD30L to CD30, which is a member of the nerve growth factor/tumor necrosis factor receptor family, induces proliferation in peripheral blood lymphocytes and Hodgkin's derived cell lines with a T-cell phenotype such as HDLM-2 and L540, while cell lines derived from anaplastic large cell lymphomas, such as Karpas 299, undergo cell death. In order to investigate whether mutations of the CD30 antigen are responsible for these opposite effects, we cloned the open reading frame of CD30 cDNAs from the cell lines L540 and Karpas 299 and from peripheral blood lymphocytes by reverse transcriptase polymerase chain reaction. Sequencing of independent plasmid clones revealed that these cells have a silent transition (A-->G) at position 771 of the open reading frame compared to the published sequence derived from the HTLV-1+ cell line HUT-102. As published data have shown that crosslinking of CD30 induces an elevation of cytosolic free calcium ([Ca2+]i) in TCR positive Jurkat cells, we have analysed the effect of crosslinking of CD30 on L540 and Karpas 299 cells. No elevations of [Ca2+]i have been observed in these cell lines after crosslinking of CD30 with HRS-4. We conclude (i) that the different functional effects of CD30 in PBL, L540 and Karpas 299 are not due to differences in the primary structure of the receptor; and (ii) that the different responses observed upon engagement with CD30L for the cell lines L540 and Karpas 299 do not correlate with differences in mobilization of [Ca2+]i after crosslinking of CD30.
 ...
PMID:Opposite effects of the CD30 ligand are not due to CD30 mutations: results from cDNA cloning and sequence comparison of the CD30 antigen from different sources. 752 1

The CD30 antigen was originally described as a specific surface marker for Hodgkin's lymphoma. Recent work established CD30 as a member of the tumor necrosis factor/nerve growth factor receptor superfamily whose ligand (CD30L) has also been cloned and expressed; CD30L is active as membrane-bound type II glycoprotein. Here, CD30L mRNA expression was studied in a panel of 102 continuous human leukemia-lymphoma cell lines and was found only in four Burkitt lymphoma, one Burkit-type acute lymphoblastic leukemia and one non-Hodgkin's lymphoma (NHL) cell line. The product of CD30L mRNA is expressed as a membrane protein on the surface of these malignant B-cell lines. Treatment of these cell lines with soluble CD27L, phorbol ester or staphylococcus aureus Cowan antigen resulted in the enhancement of cell surface CD30L protein expression. CD30L mRNA was not detected in normal unstimulated peripheral blood (PB) monocytes, monocyte-derived macrophages, or T-cells, but was detected in primary granulocytes; exposure to activating reagents induced and upregulated CD30L transcription in these different PB populations. While CD40 and CD30L surface protein expression on PB monocytes could be enhanced or induced by treatment with gamma-interferon, these cells remained negative for CD30, both at the mRNA and at the protein level. Similarly, PB monocyte-derived macrophages and granulocytes remained negative for CD30 mRNA and protein expression, regardless of stimulation. Only activated T-cells expressed CD30 mRNA and surface protein. CD30L-transfected cells and cells constitutively expressing CD30L delivered a similar stimulus for proliferation of the CD30+ Hodgkin's disease (HD)-derived cell line HDLM-2, but inhibited proliferation of the CD30+ large cell anaplastic lymphoma cell line KARPAS-299. These data provide strong evidence for the involvement in growth regulation of recombinant and natural CD30L through its interaction with the CD30 receptor. Collectively, these data suggest that the CD30L-CD30 interaction has potent biological activity and might play a critical role in the immune response and pathogenesis of HD and some NHL, in particular Burkitt lymphomas.
 ...
PMID:Expression and regulation of CD30 ligand and CD30 in human leukemia-lymphoma cell lines. 752 56


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>