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

A lack of adenosine deaminase activity has been associated with severe combined immunodeficiency and decreased enzyme activity observed in acute lymphocytic leukemia. We have measured enzyme activity in lymphocytes, red blood cells, and plasma of patients with a variety of metastatic tumors. Patients with tumor had a significantly lower erythrocyte adenosine deaminase activity (p less than 0.025) and statistically higher enzyme activity in their lymphocytes (p less than 0.010) when compared with control plasmaphoresis donors. Interestingly, blood type A tumor patients showed a significant decrease in their erythrocyte enzyme concentration compared with blood group A controls (p less than 0.001) as well as a collective group of type B and O tumor patients (p less than 0.001). Type A patient lymphocyte adenosine deaminase activity was not increased and was not statistically different from control group A donors. Tumor patients with blood groups B and O considered collectively had a statistically significant increase in their lymphocyte enzyme concentration compared with group B and O controls (p less than 0.001).
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PMID:Adenosine deaminase levels in blood type A patients with metastatic tumor. 124 85

Specific host-graft interactions, as well as intrinsic properties of transferred cell, determine tumorigenicity in xenogeneic systems. We compared the growth characteristics of human B-lymphoid cell lines in SCID mice with the well characterized growth pattern in nude mice and observed striking differences in malignancy in the respective hosts. Two cell lines derived from the same individual, the Epstein-Barr-virus(EBV)-positive Burkitt's lymphoma BL 60 (BL) and the autologous EBV-immortalized lymphoblastoid cell line IARC 277 (LCL) were used. In addition, we tested somatic cell hybrids (HYB) of both cell lines, which despite the LCL-like differentiation phenotype show the de-regulated c-myc expression pattern of the parental BL line, assumed to be a critical factor in BL pathogenesis. Subcutaneously (s.c.) injected BL cells produced local progressively growing tumor masses at the injection site without distant metastases in both nude and SCID mice. Although both mouse strains possess the same genetic background (BALB/c) and differ only in the B-cell sub-set, the growth patterns of the LCL and hybrids were completely different. In contrast to the regressive behaviour of LCL and hybrids in nude mice, these lines show invasive and disseminated progressive growth in SCID mice. Peripheral lymph nodes an thymic tissue were preferentially colonized, whereas mucosal-associated lymphoid tissue (Peyer's patches and appendix) and spleen were not infiltrated. The preferential migration of lymphocytes to certain tissues is termed homing in a syngeneic system and mediated by homing receptors and vascular addressins. The "homing" of LCL and hybrids into lymphoid SCID mouse tissue suggests a strong interaction with the endothelial cells of the host. Detailed phenotypic analysis of BL, LCL and 3 different hybrids was performed using an antibody panel against differentiation and adhesion markers. Overall dominance of the LCL phenotype was observed in the hybrids, as indicated by cytology, tumor growth, dissemination and the pattern of surface-marker expression. The c-myc activation in hybrids does not appear to influence growth behavior.
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PMID:Local growth of a Burkitt's lymphoma versus disseminated invasive growth of the autologous EBV-immortalized lymphoblastoid cells and their somatic cell hybrids in SCID mice. 130 26

Mice infected with various tumor retroviruses have been used as models for evaluating therapeutic substances for the treatment of some cancers, and more recently, for human immunodeficiency virus (HIV) infection, the causative agent of acquired immune deficiency syndrome (AIDS). Consequently, there is a need to determine the ability of biological response modifiers (BRMs) to specifically reduce virus-infected cells, as compared to their non-specific anti-proliferative effects. To address this need, a BRM, imexon, was evaluated in this study using three strains of mice having different Friend virus (FV)-specific immunological capabilities. The first strain, (B10.A x A/WySn)F1, was genetically capable of producing FV-specific neutralization and cytotoxic antibodies, the second, Balb/c, was not, and the third, SCID mice, lacked functional T and B cell immunity. Imexon treatment reduced virally-induced splenomegaly in all 3 strains; however, the concentration of splenic viral infectious centers (IC) were not affected. Since imexon was efficacious in reducing splenomegaly in SCID mice, the mode of action was concluded to not require functional T or B cell immunity. The observation that imexon did not affect splenic IC titers also suggested that imexon did not specifically eliminate virally infected cells, but may have functioned by other mechanisms. This study also demonstrated the use of various mouse strains as a strategy for delineating the modes of action of BRMs against murine retroviral infections.
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PMID:Elucidation of mode of retroviral-inhibitory effects of imexon through use of immune competent and severe combined immune deficiency (SCID) mice. 131 37

Epstein-Barr virus (EBV) is associated with B-cell malignancy in immunosuppressed humans and SCID mice receiving human peripheral blood leukocyte grafts (hu-PBL-SCID). We have further characterized the process of lymphoma development in hu-PBL-SCID mice. We report that EBV-seropositive donors differ markedly in the capacity of their PBL to give rise to immunoblastic lymphomas in SCID mice; some donors (high incidence) generated tumors rapidly in all hu-PBL-SCID mice, other donors (intermediate-low incidence) gave rise to sporadic tumors after a longer latent period (greater than 10 weeks), and some donors failed to produce tumors. B-cell lymphomas arising from high incidence donors were multiclonal in origin, and EBV replication was detected in all tumors. Tumors derived from intermediate-low incidence donors were monoclonal or oligoclonal and often had no evidence of viral replication. All tumors, regardless of the donor, resembled EBV-transformed lymphoblastoid cell lines in surface phenotype but differed from lymphoblastoid cell lines by having less Epstein-Barr nuclear antigen 2 and CD23 expression. The variable patterns of lymphomagenesis seen among different EBV-sero-positive donors may be explained by lower levels of specific immunity to EBV in high incidence donors, permitting activation of EBV replication and potential transformation of secondary B-cell targets. In addition, there may be differences in the transforming potential of EBV infecting different donors. The use of the hu-PBL-SCID model may help predict patients at high risk for posttransplant or acquired immunodeficiency syndrome-associated lymphomas.
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PMID:Heterogeneity among Epstein-Barr virus-seropositive donors in the generation of immunoblastic B-cell lymphomas in SCID mice receiving human peripheral blood leukocyte grafts. 131 93

We analyzed the karyotype of 27 B-cell lymphomas of human origin that developed in mice with severe combined immunodeficiency disease following the injection of peripheral blood leukocytes from Epstein-Barr virus-seropositive donors. Three tumors had clonal abnormalities detected with conventional techniques, 2 had trisomy 11, and 1 had a del(6)(q21q25). One other tumor had trisomy 11 detected with fluorescence in situ hybridization. Twelve tumors had a normal karyotype, 11 tumors had nonclonal abnormalities (which included trisomy 9 or 12 in 3 or 2 tumors, respectively), and one tumor had a karyotype of 92,XXXX(75%)/46,XX(25%) by conventional cytogenetic analysis. Trisomy for chromosomes, 9, 11, and 12 are recurring abnormalities that have been observed in lymphomas associated with an immunocompromised state. Clonal or nonclonal abnormalities were observed in 8 of 11 tumors derived from 3 donors whose peripheral lymphocytes induced a high incidence of tumors in mice with severe combined immunodeficiency disease compared with a clonal abnormality and 2 nonclonal abnormal cells in 2 of 5 tumors derived from 3 donors whose lymphocytes induced an intermediate to low incidence. These observations suggest an association between a higher incidence of karyotypically abnormal cells in lymphomas and the increased tumorigenic potential of the lymphocytes that induced these tumors.
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PMID:Cytogenetic characterization of B-cell lymphomas from severe combined immunodeficiency disease mice given injections of lymphocytes from Epstein-Barr virus-positive donors. 132 90

Severe combined immunodeficiency (scid) mice develop EBV (+)B cell tumors after infusion of EBV(+)B cells or of B cells and EBV. In this study, scid mice were infused with B cell lines derived from three patients who developed a B lymphocyte proliferative disorder after bone marrow or organ transplantation. Intraperitoneal injection of 5 x 10(6) B cells induced tumor growth in all mice, leading to death within 60 d. Human B cells were identified in spleen and bone marrow by means of immunofluorescence or EBV genome amplification, and human IgM was detected in serum. Infusion of murine monoclonal antibodies specific for human B cell membrane antigens CD21, CD24, and CD23 was effective in 80% of animals, against two of the three cell lines preventing tumor development or inducing remission according to the time of treatment. The effect was antibody dose dependent and was optimal with four intravenous infusions of at least 0.1 mg 4 d apart. Human IgM in serum and human B cells in spleen and bone marrow became undetectable when peritoneal tumors regressed completely. Infusions of IgG1 isotype-matched anti-CD4 antibody or anti-CD3 antibody had no effect. Tumors developed or recurred in 50% of these animals injected with one of the B cell line 3 mo after treatment was stopped. The same anti-CD21 and anti-CD24 antibodies had been used to treat the three patients, and shown similar degrees of effectiveness as in the scid mouse model. These results indicate that scid mice may be suitable for assessing therapeutic approaches to human B cell proliferation.
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PMID:Control of human B cell tumor growth in severe combined immunodeficiency mice by monoclonal anti-B cell antibodies. 132 2

Epstein-Barr virus (EBV) infection is associated with immunoblastic B-cell lymphomas in immunosuppressed or human immunodeficiency virus-infected individuals and in SCID mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID) from EBV-seropositive donors. The risk of tumors appearing in the hu-PBL-SCID mice differs among EBV-seropositive donors. Four different outcomes have been noted: (a) no tumors appear (no incidence donors); (b) tumors appear in a fraction of hu-PBL-SCID mice with a 10-20 week latent period (low- and intermediate-incidence donors); or (c) tumors appear in all hu-PBL-SCID mice within 6-10 weeks (high-incidence donors). The latter category of rapidly appearing tumor invariably involved activation of EBV replication, whereas more slowly growing tumors rarely activated EBV. The results indicate that prospective screening of high-risk individuals in the hu-PBL-SCID model may predict the risk of EBV-associated lymphoma development.
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PMID:Epstein-Barr virus-induced human B-cell lymphomas in SCID mice reconstituted with human peripheral blood leukocytes. 132 10

Injection of Epstein-Barr virus (EBV)-transformed human lymphoblastoid B cells into immunodeficient SCID mice results in the appearance of rapidly growing, fatal human B-cell tumors. To evaluate the role of EBV nuclear protein 2 (EBNA-2) in this process, we generated lymphoblastoid cell lines transformed by several EBV mutants which were identical except for deletions in the EBNA-2 gene (J. I. Cohen, F. Wang, and E. Kieff, J. Virol. 65:2545-2554, 1991). These cell lines were injected intraperitoneally into SCID mice, and the interval until tumor detection was determined. Cell lines transformed with EBV type 1 (strain W91) or with EBV type 2 (strain P3HR-1) with an inserted type 1 EBNA-2 gene grew at the same rapid rate, indicating the potential importance of EBNA-2 for tumor formation in vivo. Cell lines derived from three different EBV mutants with deletions in the amino half of EBNA-2 produced tumors more slowly than cell lines transformed by wild-type W91 virus. In contrast, a cell line transformed with an EBV mutant with a deletion in the carboxy terminus of EBNA-2 grew more rapidly than cell lines transformed by wild-type virus. EBV mutants with deletions in the amino half of EBNA-2 had had reduced transforming activity in vitro, while the carboxy-terminal EBNA-2 mutant had had transforming activity greater than or equal to that of the wild type. These data indicate that EBNA-2 plays a critical role both for B-cell tumor growth in SCID mice and for B-lymphocyte transformation in vitro.
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PMID:Epstein-Barr virus nuclear protein 2 is a critical determinant for tumor growth in SCID mice and for transformation in vitro. 133 38

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

We have examined the antimetastatic effects of taxol on a PC-3 human prostatic tumor variant (PC-3 ML) which metastasizes to the lumbar vertebrae in severe combined immunodeficiency-carrying (SCID) mice. Immunofluorescence labeling indicated that taxol (0.5 to 1.0 microM for 6 h) produced an abnormal bundling of microtubules in a dosage-dependent manner. Slot blotting and gelatinase assays revealed that taxol inhibited secretion of the M(r) 72,000 and M(r) 92,000 type IV collagenases plus a M(r) 57,000 gelatinase. Radioimmunoprecipitation measurements confirmed that the drug inhibited both the secretion and the synthesis of the M(r) 72,000 collagenase. Taxol also blocked total protein secretion but did not influence total protein synthesis or turnover. Boyden chamber chemotactic studies further showed that taxol (0.5 to 1.0 microM) inhibited invasion of Matrigel. More importantly, studies in SCID mice demonstrated that taxol (50 to 250 mg/m2/day) blocked the establishment, growth, and long-term survival of PC-3 ML cells.
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PMID:Taxol blocks processes essential for prostate tumor cell (PC-3 ML) invasion and metastases. 135 84


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