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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined a possible role for the adhesion molecules LFA-1 and ICAM-1 in localizing central nervous system non-Hodgkin's lymphomas (CNS-NHLs) to the brain. Fresh frozen sections from 12 monoclonal CNS NHLs (11 primary, one secondary) were stained with monoclonal antibodies to LFA-1 alpha chain (CD11a), beta chain (CD18) and, ICAM-1 (CD54). Additional staining made use of rat monoclonal antibodies to the human and mouse high endothelial venule antigens HECA 452 and MECA 79 and mouse ICAM-1. The expression of these same molecules was also studied in mice with severe combined immunodeficiency (SCID) mice, bearing intracranial human lymphoblastoid cells. Eleven of the CNS-NHL tumors expressed LFA-1 alpha (one strongly, one intermediate, nine weakly). Nine of the tumors weakly expressed LFA-1 beta.. Nine of twelve tumors weakly expressed ICAM-1. In six of seven tumors definite blood vessels stained for ICAM-1. Non-tumor brain from two patients and non-tumor cerebral blood vessels showed no staining with CD11a, CD18 or CD54 antibodies. Strong expression of LFA-alpha and LFA-beta as well as ICAM-1 was noted in human lymphoblastoid cells (LCLs)/SCID mouse CNS lymphomas. Tumor blood vessels in these mice stained for mouse ICAM-1. Normal SCID mouse brains showed no staining with CD11a, CD18, CD54 or mouse ICAM-1 antibodies. Human, human/mouse CNS lymphomas, normal human, and mouse brains showed no staining with either HECA 452 or MECA 79.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of LFA-1/ICAM-1 in CNS lymphomas: possible mechanism for lymphoma homing into the brain. 134 29

Until now there has been no satisfactory animal host for the in vivo growth of Hodgkin lymphoma cells. With the exception of one mutant subline (L540Cy) none of the other Hodgkin derived cell lines nor Hodgkin's disease (HD) derived lymphatic tissue could be propagated in suitable animal systems such as the T-cell deficient nude mouse. Recently, the severe combined immunodeficient (SCID-) mouse has been demonstrated as a possible recipient for human lymphatic tissue. In the present study, we have evaluated the SCID mouse as a possible in vivo model for Hodgkin's lymphoma. I) We demonstrate that seven permanent cell lines derived from patients with Hodgkin's disease grow progressively in SCID mice after subcutaneous and intraperitoneal inoculation. II) In addition, after intravenous injection, two of these lines (L540, L540Cy) show a disseminated growth pattern resembling the distribution of HD cells in man (involvement of lymph nodes, liver and bone marrow but not of spleen). The observed reproducible disseminated tumor growth establishes the SCID mouse as a new animal model for experimental treatment strategies in Hodgkin's lymphoma. III) We present preliminary results of the transplantation of primary material from 13 patients with Hodgkin's disease. Material from two patients induced human tumors in the SCID mice recipients, whereas material from two others led to the induction of mouse lymphomas. The human tumors showed three distinct histological patterns: 1) Lymphoproliferative disease (LPD); 2) anaplastic large cell lymphomas (ALCL); 3) Hodgkin like lesions (HLL). In vitro cell lines established from human SCID mouse tumors were of B-lymphoid origin, were EBV-positive and showed numerical and some structural chromosomal aberrations of varying degree.
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PMID:Preliminary report: growth of Hodgkin's lymphoma derived cells in immune compromised mice. 145 76

In the present paper, the authors describe the production and testing of immunotoxins for clinical application in Hodgkin's disease. The immunotoxins were constructed by chemical coupling of deglycolysated ricin-A to monoclonal antibodies against antigens on Hodgkin's and Reed-Sternberg cells (CD25, CD30, IRac). The cytotoxic effect of the immunotoxins was investigated in vitro against Hodgkin's and Reed-Sternberg cells (H-RS) and in vivo against solid Hodgkin's tumors in nude mice and disseminated Hodgkin's tumors in SCID mice. Cross-reactivity with normal tissue and the staining behaviour observed in sections of Hodgkin's tissue of various subtypes proved important parameters for the assessment of clinical applicability. Of more than 30 evaluated MoAb's, eight immunotoxins were produced, of which six showed both, cytotoxic effects of considerable potency against Hodgkin's tumor cells and low cross-reactivity with vital human organs. The most effective immunotoxin, RFT5 gamma 1.dgA, (CD25) inhibits the growth of H-RS cells at concentrations of 7 pMol and destroys about 60% of solid Hodgkin's tumors of 0.5 cm in diameter in nude mice. This immunotoxin binds to virtually all tumor cells in more than 90% of patients with Hodgkin's disease. Sufficient quantities of RFT5 gamma 1.dgA were produced for the treatment of patients with refractory Hodgkin's disease. These patients are currently being treated in a phase I clinical trial.
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PMID:[New perspectives in oncology: is selective destruction of tumor cells with immunotoxins in Hodgkin's disease an additional therapeutic alternative?]. 146 Dec 15

Canine lymphoid tumours, which share a number of features with human non-Hodgkin's lymphomas, were grafted in nude or SCID mice. Two (DL.24,DL.31) out of eight lymphomas and two (DL.31,DL.35) out of three lymphomas produced a sub-cutaneous (s.c.) tumour in nude and SCID mice respectively. In all animals, the s.c. tumours that developed at the inoculation site were regularly associated with metastasis to the regional lymph nodes, and also to the spleen, liver and bone marrow in SCID mice. The four transplanted tumours, with a pseudo-diploid canine karyotype, were diffuse large cell lymphomas as the initial dog tumours, and could be immunophenotypically characterized by surface immunoglobulins, MHC-class 2 and Thy-1 antigens. Serially transplanted lymphomas in nude and SCID mice may hence be used for further studies of these tumours.
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PMID:Transplantation of canine malignant lymphomas in the nude and SCID mouse. 162 46

The anatomical distribution, morphology, and clonality, of 'non-Hodgkin's lymphomas' in immunocompromised patients are usually distinctly different from NHL occurring in the general population. Mosier DE, Gulizia RJ, Baird SM, Wilson DB: Nature (London) 335:256, 1988 have described lymphoproliferative disease (LPD) of human B cell origin in mice with severe combined immunodeficiency (scid mice) after transfer of human peripheral blood mononuclear cells from Epstein-Barr virus-seropositive individuals. Reported herein is detailed information regarding the morphology, phenotypes, and clonality of LPD lesions in 10 of 18 scid mice that had developed LPD after transfer of peripheral blood mononuclear cells. These lesions were diffuse and monomorphic proliferations of immunoblastoid cells. They were invasive in their growth and often necrotic. Human B cell-related and activation-associated antigens were found on the LPD lesions, although the numbers of cells with the latter antigens were relatively small. Immunofixation electrophoresis for human immunoglobulins in sera of the majority of mice revealed oligoclonal populations, however, phenotypic and cytogenetic analyses showed no definite monoclonality. This scid mouse model is beneficial for understanding the early phases in the pathogenesis of LPD in immunocompromised patients.
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PMID:Hematopathologic features of Epstein-Barr virus-induced human B-lymphoproliferation in mice with severe combined immunodeficiency. A model of lymphoproliferative diseases in immunocompromised patients. 165 38

The association between cancer and immunodeficiency is well established. In common variable immunodeficiency (CVI), a primary immunodeficiency disease characterized by low serum immunoglobulins and poor antibody production, we previously reported a total of 13 cancers in 11 individuals arising in continuously observed group of patients. Of the 13, 7 were NHL and 1 was a myeloma which progressed to lymphoma. We report here the histologic, immunologic, cytogenetic, and clinical features of these 8 NHL along with 3 new lymphomas which have appeared in this group (now 117 patients). From our studies, the lymphomas which have arisen in CVI share certain features with the lymphomas which appear in the childhood immunodeficient syndromes. Wiskott Aldrich Syndrome, Ataxia Telangiectasia, or severe combined immunodeficiency: they are similar in overall frequency (13%), are often B-cell in origin, and extranodal in location. However, unlike the lymphomas of the immunodeficient child, lymphomas in CVI may be more differentiated and secrete immunoglobulin. For CVI patients with stage I or II disease, as for non-Hodgkin lymphomas in general, the prognosis is good. In our group, NHL in CVI have appeared most often in females of the 5th to 7th decade and not in childhood. Cytogenetic studies in lymphomas show that cytogenic abnormalities, including chromosomal translocation, can be found in this group, but more studies will be needed to assess the frequency of these events.
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PMID:Non-Hodgkin lymphoma in common variable immunodeficiency. 182 73

Individuals with either primary or secondary immunodeficiencies are at high risk to develop not only infections but also malignancy (especially of the lymphoid system). The major focus of this paper is on malignancies that develop in immunodeficiency syndromes, particularly malignancies in naturally occurring immunodeficiencies and following bone marrow transplantation (BMT). As of August, 1986, 514 cases of naturally occurring immunodeficiencies have been registered at the Immunodeficiency Cancer Registry. Overall non-Hodgkin's lymphomas predominate in these patients, accounting for 48.6% of all cases. Non-Hodgkin's lymphoma is the predominant malignancy in ataxia-telangiectasia, common variable immunodeficiency, Wiskott-Aldrich syndrome (WAS) and severe combined immunodeficiency (SCID). The histopathology of the lymphomas differs somewhat in each of the disorders. In WAS, large cell "histiocytic" lymphoma predominates, with most cases having the features of B lymphocytes, including pleomorphic immunocytoma and immunoblastic lymphoma. Non-Hodgkin's lymphoma in SCID also generally has B cell features and in some cases multiple copies of Epstein-Barr virus (EBV) genomic DNA have been found in tumor tissue. In contrast to ataxia-telangiectasia, in which non-Hodgkin's lymphoma is also the predominant neoplasm, the morphology and cell marker characteristics are more similar to those seen in nonimmunodeficient children. The lymphomas in ataxia-telangiectasia are very heterogeneous with representation from all the major histologic subtypes. We have found no relationship between the degree of immunodeficiency and the development of malignancy. Immunodeficiency following BMT, as in naturally occurring immunodeficiencies, appears to predispose patients to the development of lymphoid malignancy, especially for recipients of partially mismatched bone marrow. In Minnesota 8 patients have developed B cell lympho-proliferative disorders (BLPD) following BMT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship of immunodeficiency to lymphoid malignancy. 284 Jun 29

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.
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PMID:Disseminated growth of Hodgkin's-derived cell lines L540 and L540cy in immune-deficient SCID mice. 751 37

Epstein-Barr Virus (EBV) is implicated in the pathogenesis of endemic Burkitt's lymphoma (BL), B-cell lymphomas occurring under immunosuppression, nasopharyngeal carcinoma and Hodgkin's disease. Two distinct patterns of latent EBV gene expression occur in EBV-associated lymphomas. BLs typically display expression of the nuclear antigen EBNAI only, whereas EBV-associated, non-Burkitt B-cell lymphomas express at least 9 latent viral genes (6 EBNAs and 3 latent membrane proteins), reminiscent of in vitro EBV-immortalized lymphoblastoid cell lines (LCL). BLs are characterized by local, extra-nodal growth, whereas EBV-associated B-cell lymphomas often disseminate to peripheral lymphoid tissue. We show here that BL cells forming local tumors after xenotransplantation into SCID mice disseminate to lymphoid tissue following introduction of the latent membrane protein I (LMP 1) gene. Introduction of LMP 1 into BL cells induced expression of CD44 on the cell surface, a molecule implicated in enhanced lymphoid tumor growth and dissemination. Introduction of CD44 into LMP 1-/CD44-BL cells was observed to confer the disseminated tumor growth pattern associated with LMP 1 expression. Taken together our results show that expression of LMP 1 may regulate expression of CD44 and play an important role in the behavior of EBV-based lymphomas.
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PMID:Induction of CD44 expression by the Epstein-Barr virus latent membrane protein LMP1 is associated with lymphoma dissemination. 753 55

The lymphocyte activation marker CD30 has been shown to be an excellent target for the immunotherapy of human Hodgkin's lymphoma. In order to develop new potent immunotoxins (ITs) against CD30, we chemically linked 6 recently described monoclonal antibodies (MAbs) via SMPT to deglycosylated ricin A-chain (dgA). Cross-blocking experiments demonstrated that these MAbs, termed Ki-2 to Ki-7, recognize 3 different clusters on the CD30 antigen: Ki-2, Ki-4, Ki-5 and Ki-7 recognize cluster A; Ki-6 recognizes cluster B; Ki-3 binds to cluster C. Staining of 29 sections of normal human organs revealed no major cross-reactivity of any MAbs tested. Binding to the CD30 antigen on L540Cy Hodgkin cells was assessed by flow cytometry, and demonstrated high affinities for Ki-2, Ki-3 and Ki-4. The concentration giving 50% of the mean fluorescence intensity (MFI50) was 0.58 micrograms/ml to 0.78 micrograms/l. MAbs Ki-5, Ki-6, and Ki-7 bound much more weakly. The staining intensity of the MAbs correlated with the cytotoxicity of the corresponding ITs. Ki-2.dgA, ki-3.dgA and Ki-4.dgA inhibited the protein synthesis of L540Cy cells by 50% at concentrations (IC50) of 3.5 x 10(-10)M to 4.0 x 10(-11)M. The most effective IT, Ki-4dgA, is 5-fold more potent than previously reported CD30 ricin A-chain ITs. Ki-4.dgA was subsequently used for the treatment of disseminated human Hodgkin's lymphoma in a SCID mouse model. The mean survival time (MST) of lymphoma-bearing SCID mice was extended from 42 days in untreated controls to more than 132 days when Ki-4.dgA was applied one day after tumor challenge. Ki-4.dgA is a new potent IT suitable for further evaluation against Hodgkin's lymphoma in man.
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PMID:Development of new ricin A-chain immunotoxins with potent anti-tumor effects against human Hodgkin cells in vitro and disseminated Hodgkin tumors in SCID mice using high-affinity monoclonal antibodies directed against the CD30 antigen. 759 Dec 11


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