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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor effects of two anti-CD22 ricin A chain-containing immunotoxin (IT) constructs were compared in mice with severe combined immunodeficiency disease with human Daudi cell tumors (SCID-Daudi mice). SCID-Daudi mice develop disseminated lymphoma that clinically resembles African Burkitt's lymphoma, i.e., extranodal disease including infiltration of the vertebral column and spinal canal. In the absence of treatment, the mean survival time of SCID-Daudi mice was 45.9 +/- 4.3 days. The mice was given injections of a dose of IT equal to 40% of the 50% lethal dose. The ITs consisted of either IgG or Fab' fragments of mouse anti-CD22 antibody coupled to deglycosylated ricin A chain (dgA). Both ITs were potent and specific and inhibited protein synthesis in Daudi cells in vitro by 50% at concentrations of 1.2 x 10(-12) (IgG-dgA) and 1.3 x 10(-11) M (Fab'-dgA). When administered to mice beginning 1 day after inoculation with tumor cells, both ITs extended the mean survival time, to 87.2 +/- 18.9 days (IgG-dgA) or 57.9 +/- 3.8 days (Fab'-dgA). The latter represented the killing of 2 logs of Daudi cells, and the former 4 logs. IgG antibody alone killed 1 log of tumor cells. The IgG-dgA had an antitumor effect even when administered 20-23 days after tumor inoculation. Gross and histological examinations of IT-treated tumor-bearing mice showed a marked decrease in the number and size of neoplastic foci in both lymphoid organs and extranodal sites.
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PMID:Antitumor activity of Fab' and IgG-anti-CD22 immunotoxins in disseminated human B lymphoma grown in mice with severe combined immunodeficiency disease: effect on tumor cells in extranodal sites. 193 55

The aim of this study was to analyze the homing and progression patterns of childhood acute lymphoblastic leukemias (ALL) in mice with severe combined immunodeficiency (SCID). Upon intraperitoneal (IP) transfer, cells from relapse samples of three children with T-lineage ALL spread hematogenously and infiltrated the non-lymphoid and/or lymphoid organs with a pattern reminiscent of the human clinical disease. These mice either died or were killed in extremis at a mean of 9 weeks. Moreover, cell lines established in vitro from two of these samples manifested identical homing and progression in the SCID mouse as compared with the original patients' cells. Thus, long-term culture of the primary leukemic T cells did not alter their invasive potential and migration pattern. When engrafted IP, three cell lines established from pre-B-ALL cases displayed primarily a lymphatic spread with induction of local tumor masses and kidney/liver nodules. Mice were killed at 11 to 13 weeks, but had not developed imminently fatal leukemia. However, when transferred intravenously, one pre-B ALL cell line was able to spread hematogenously and to infiltrate both lymphoid and non-lymphoid tissues. Overall, these data demonstrate that the SCID mouse provides an efficient and reproducible model to study the pathogenesis of childhood ALL, and may be a suitable system for evaluating therapy.
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PMID:Homing and progression patterns of childhood acute lymphoblastic leukemias in severe combined immunodeficiency mice. 203 29

In severe combined immunodeficiency (scid) mice which are deficient in T and B cell functions, human yolk sac tumor (YST-2) grew rapidly to enormous sizes in all of the animals after both subcutaneous and intraperitoneal transplantation, while only half of the subcutaneous and none of the intraperitoneal transplants were accepted in usual athymic nude mice. Furthermore, transplanted tumors metastasized spontaneously to distant organs such as lung, liver, kidney, pancreas, and spleen in scid mice, while metastases were not found in athymic nude mice. Similar results were observed in scid mice and scid-nude (streaker) double mutant mice with human classic (typical) seminoma which has been neither transplantable nor metastatic in athymic nude mice. Thus, scid mice provide an invaluable experimental system to investigate the mechanism of metastasis which is the most important and life-threatening problem in cancer patients.
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PMID:SCID (severe combined immunodeficiency) mice as a new system to investigate metastasis of human tumors. 224 54

A human Burkitt lymphoma (Daudi) has been grown in the mutant mouse called C.B-17 SCID. Twenty-eight days after s.c. injection of Daudi cells, a palpable tumor grew only at the site of injection in all injected mice. In contrast, after intravenous (i.v.) or intraperitoneal (i.p.) injection, macroscopic, disseminated tumors developed. Following i.v. inoculation, tumors grew in the lungs, kidneys, ovaries and adipose tissue, and microscopic tumor infiltrates were observed in the spleen, bone marrow, spinal column and femur, whereas after i.p. injection, the tumors were localized in the abdomen, liver, spleen, ovaries and muscular tunics of the gut, but did not disseminate into the lung or bone marrow. The growth pattern and phenotype of the Daudi cells were similar whether the inoculated tumor cells were derived from the in vitro cell line or from in vivo passaged tumors. The survival time of the tumor-bearing animals was dependent on the dose of i.v.-administered Daudi cells; as few as 100 cells caused death. All mice injected i.v. showed paresis or paralysis of the hind legs just prior to death. This was associated with the presence of neoplastic nodules within the spinal canal. Two surface antigens on Daudi cells (CD19 and CD22) were stably expressed in all the neoplastic lesions. Radiolabelled anti-CD22 antibodies localized in organs infiltrated with tumor, but did not penetrate primary s.c. tumors. This model of disseminated vs. solid tumor should prove useful for evaluating the efficacy of different types and doses of therapeutic antibodies, immunoconjugates and immunotoxins prepared from anti-human B-cell antibodies.
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PMID:Disseminated or localized growth of a human B-cell tumor (Daudi) in SCID mice. 230 38

Histologic findings in mice with severe combined immunodeficiency (SCID) were remarkably uniform, consisting of lymphopenia, a rudimentary thymic medulla without cortex, relatively empty splenic follicles and lymph nodes, and undeveloped bronchial and gastrointestinal lymphocytic foci. Fluorescence-activated cell sorter studies revealed a few T cells (apparently nonfunctional) in thymus and spleen; interestingly, these cells seemed highly disposed to neoplasia, because thymic T-cell lymphomas were observed in 41 of 269 mice. No pre-B or B cells could be identified. Cells of the myeloid lineage appeared normal. Reconstitution of lymphoid tissues was achieved after intravenous injection of histocompatible bone marrow cells.
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PMID:Severe combined immunodeficiency (SCID) in the mouse. Pathology, reconstitution, neoplasms. 241 48

We examined the effect of type I IFN inducers and rIFN-alpha on MHC expression in mouse tissues in vivo. MHC expression was assessed in a radiolabeled mAb binding assay and by indirect immunoperoxidase staining of tissue sections. polyI:C, an inducer of IFN-alpha/beta, induced large increases in class I MHC in many tissues, with little effect on class II expression. In the kidney, which was studied in detail, polyI:C increased class I expression from day 1 to day 6, localized in glomeruli, tubules, and arterial endothelium. Renal class II MHC was less affected but tended to be decreased at days 3 to 6, corresponding to diminished staining of class II-positive interstitial cells. polyI:C increased renal class I MHC in nude mice and mice with severe combined immunodeficiency, and in mice treated with cyclosporine or mAb against IFN-gamma. The effects of influenza virus resembled those of polyI:C. However, a potent T cell stimulus, allogeneic ascites tumor cells, induced markedly different MHC changes, with massive and sustained increases in class I and II, presumably due to IFN-gamma release, which was inhibited by cyclosporine or by mAb against IFN-gamma. The effect of polyI:C was largely simulated by rIFN-alpha, whereas the effect of allogeneic cells was simulated by rIFN-gamma. Thus, rIFN-alpha and its inducers in vivo produce a sustained increase in renal class I expression in kidney and other tissues, sometimes with changes in class II expression. Such effects could be relevant to the immune modulatory actions of IFN, and to the immunologic consequences of viral infections.
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PMID:Regulation of MHC expression in vivo. II. IFN-alpha/beta inducers and recombinant IFN-alpha modulate MHC antigen expression in mouse tissues. 249 28

Mice with severe combined immunodeficiency (C.B-17 scid, hereafter SCID) accept xenografts of adult human peripheral blood leukocytes (PBL). The transplanted human PBL expand in number and survive for at least thirteen months and have been shown to reconstitute human immune function at both the T and B cell levels. Human immunoglobulin production is restored, and secondary antibody responses to antigens such as tetanus toxoid can be induced. All SCID mice reconstituted with 50 x 10(6) or more PBL from donors with evidence of exposure to Epstein-Barr virus (EBV) have developed human B cell lymphomas at 8-16 weeks after PBL engraftment, whereas mice reconstituted with PBL from EBV-seronegative donors fail to develop tumors. These tumors involve both lymphatic and non-lymphatic organs, and histologically they resemble large cell or immunoblastic lymphomas. The tumors are associated with high levels of human immunoglobulin secretion and serum electrophoresis reveals oligoclonal immunoglobulin banding patterns. Analysis of tumor DNA shows the presence of EBV genomes and oligoclonal patterns of immunoglobulin JH gene rearrangement. Taken together, these observations suggest an EBV-related proliferation of B lymphocytes leading to the rapid appearance of oligoclonal B cell malignancies following transfer of B lymphocytes from "normal" donors to SCID mice. SCID mice reconstituted with PBL from EBV-seronegative donors have been infected with the LAV-1 strain of human immunodeficiency virus (HIV-1). Virus has been recovered from most infected animals by co-culture of mouse tissue with human T lymphoblasts. Some mice with high virus titers have developed an acute wasting syndrome and depletion of human T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies of HIV infection and the development of Epstein-Barr virus-related B cell lymphomas following transfer of human lymphocytes to mice with severe combined immunodeficiency. 255 38

Patients with congenital and acquired immunodeficiencies are at increased risk for the development of B-cell lymphoproliferative disorders. When the appropriate tests have been performed, the Epstein-Barr virus (EBV) nuclear antigen (EBNA) or EBV DNA has been found in tissues from these tumors. These data have provided support for the idea that these tumors are associated with EBV. In this article we report about a child with severe combined immunodeficiency (SCID) who developed a malignant B-cell lymphoma that was not associated with EBV. The B-cell lymphoma in the patient proved to be, by hybridization analysis of immunoglobulin (Ig) heavy chain gene rearrangements of tumor-cell DNA, of clonal origin. However, neither EBNA nor EBV DNA could be detected in tumor tissue by anticomplement immunofluorescence or in situ cytohybridization with an EBV DNA probe. Furthermore, EBV DNA could not be detected by Southern blot hybridization using two EBV DNA hybridization probes on the same DNA blots that clearly contained the clonal Ig gene rearrangement. This case represents a clonal B-cell lymphoma occurring in a severely immunodeficient patient that was not associated with EBV. Antiviral chemoprophylaxis has been recommended for the prevention of EBV-related B-cell lymphoproliferations in transplant patients. Such prophylaxis may be ineffective in patients with B-cell lymphoproliferative disorders not associated with EBV.
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PMID:B-cell lymphoma in severe combined immunodeficiency not associated with the Epstein-Barr virus. 282 20

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

A small subpopulation (about 2%) of normal CD3+ human T lymphocytes lacks both CD4 and CD8 antigens. We have cloned these cells from peripheral blood lymphocytes (PBL) obtained from healthy individuals and from a patient with severe combined immunodeficiency. Six out of seven CD3+4-8-clones exert strong cytolytic activity against a variety of so-called NK-susceptible and -nonsusceptible tumor target cells. Their target cell specificity spectrum can virtually be as wide as that of CD3-NK cell-derived clones, with strong lytic capacity. Some of these clones also exert antibody-dependent cellular cytotoxicity (ADCC), a characteristic of NK cell-derived clones but not of CD3+4+ or CD8+ mature T cell-derived clones. Such CD3+ T cell clones do not express the CD16 (IgG Fc receptor) antigen, but as we demonstrate here, the CD16 antigen can be identified on CD3+4-8-clones. Both ADCC activity and CD16 antigen expression are lower in CD3+4-8- than in CD3- NK cell clones. Lytic activity of mature CD3+4+ or CD8+ and CD3- NK cell clones can be augmented, respectively, by anti-CD3 or anti-CD16 monoclonal antibodies (MAb), but that of CD3+4-8- clones are augmented by both MAb. Lytic activity of CD3+4+ or CD8+ clones is considerably enhanced after 3 hr of incubation with recombinant IL 2, as found for CD3- NK cells. Enhancement of lytic activity of allospecific CD3+4+ or CD8+ clones requires 18 hr of incubation. Thus, CD3+4-8-16+ cells share several features with CD3- NK cells. However, they express the CD3 antigen, which is characteristic for CD4+ or CD8+ mature T cells. Our results also indicate that although CD3+4-8- clones react with five preparations of anti-CD3 MAb tested, these clones do not express a classical CD3+/Ti alpha, beta antigen receptor complex. This is suggested by the finding that the CD3+4-8- clones do virtually not express the common epitope of the T cell receptor alpha, beta-chains as identified by the WT31 MAb. These CD3+4-8- lymphocytes may represent functionally mature lymphocytes of a distinct T cell subpopulation having a particular immune function.
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PMID:Lysis of tumor cells by CD3+4-8-16+ T cell receptor alpha beta- clones, regulated via CD3 and CD16 activation sites, recombinant interleukin 2, and interferon beta 1. 294 18


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