Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transgenic mice bearing a mutant, activated N-ras oncogene directed to express within hematopoietic cells by an immunoglobulin enhancer (E mu) sporadically develop T-cell lymphomas and non-lymphoid tumors that may be of macrophage origin. To identify genes that can collaborate with N-ras in hematopoietic neoplasia, Moloney murine leukemia virus was used as an insertional mutagen. Infection of newborn E mu-N-ras mice with the virus greatly accelerated tumorigenesis, and nearly all the tumors proved to be T-cell lymphomas. Their variable surface phenotype (CD4+CD8-, CD4+CD8+ and CD4-CD8-) suggested that cells at several stages of T-cell development were susceptible to tumorigenesis. Southern blot analysis revealed that 68% of the tumors bore a proviral insert 5' to the c-myc gene, while 13% had an insert within the 3' untranslated region of the N-myc gene. Insertion was associated with elevated expression of these genes. Hence, activation of a myc gene appears to be the dominant pathway to tumorigenesis by insertional mutagenesis in lymphoid cells expressing a mutant ras gene. However, since many of the tumors were not transplantable, even the partnership of myc and ras may not suffice for full lymphoid malignancy.
 ...
PMID:Retroviral infection accelerates T lymphomagenesis in E mu-N-ras transgenic mice by activating c-myc or N-myc. 157 Jan 58

Squamous cell carcinoma of the head and neck produces a prostaglandin, PGE2, a potent inhibitor of cellular immune responses. We tested the effects of prostaglandin synthetase inhibition on the infiltration of squamous cell carcinoma of the head and neck with host lymphocytes. Tumor tissue samples were obtained from six patients (age range, 51 to 72 years) who presented with squamous cell carcinoma of the head and neck before and after 14 days of treatment with indomethacin (50 mg administered orally three times a day). Tumor-infiltrating immune cells were assayed in frozen tissue samples by indirect immunofluorescence. An eightfold increase in CD2+ lymphocytes compared with pretreatment tissue was observed. The number of CD4 and CD8 lymphocytes increased similarly. CD57 lymphocytes increased 15-fold and CD11b cells increased 11-fold. No infiltrating B-cell populations were evident. Double-labeling studies revealed that the mononuclear cells were located outside blood vessel walls, indicating that they had infiltrated the tumor parenchyma. Our findings demonstrate that the administration of indomethacin is associated with the increased immune cell infiltration of squamous cell carcinoma of the head and neck. This suggests that inhibition of PGE2 synthesis as it occurs in the tumor and or systemically may contribute to the homing of mononuclear cells to the tumor. These data suggest a mechanism to account for the clinical response to indomethacin previously reported in squamous cell carcinoma.
 ...
PMID:Administration of a prostaglandin synthetase inhibitor associated with an increased immune cell infiltrate in squamous cell carcinoma of the head and neck. 157 Nov 28

The regeneration of the liver is frequently observed after the resection of liver tumor and partial liver transplantation, and it is assumed that the modification of the hematolymphoid system in the liver will occur during this process and influence not only the progress of the primary disease but also liver regeneration itself. In this study, we investigated by flow cytometric analysis the modification of the cell subpopulation in the peripheral blood lymphocytes (PBL), intrahepatic lymphocytes fraction 1, which come into marginal contact with the liver (IHL Fr. 1), and intrahepatic lymphocytes fraction 2, which come into close contact with the liver (IHL Fr.2). (1) The positive cells of each antigen (Thy 1.2, alpha beta TCR, gamma delta TCR, CD4 and CD8) exist in the normal liver as PBL. (2) CD8/CD4 ratio is 0.3-0.4 in PBL and IHL Fr.1 and significantly higher in IHL Fr.2 (0.7). (3) Compared with other fractions, the ratio of alpha beta TCR dull positive cells to whole alpha beta TCR positive cells is low, while (4) the percentage of gamma delta TCR positive cells is high in IHL Fr.2. These facts suggest that lymphocyte populations in the liver differ from those of PBL. Furthermore, one day after partial hepatectomy, (5) the percentage of the alpha beta TCR dull positive cells decreases in PBL, but remarkably increases to 2.6 times the normal level in IHL Fr.2 and (6) the ratio of CD8/CD4 increases to 1.4 times in IHL Fr.2. (7) The percentage of gamma delta TCR positive cells decreases in PBL, but does not significantly change in IHL Fr. 2 during the liver regeneration. These findings reveal that lymphocyte populations different from PBL exist in the liver and respond to stimulus to the liver in different ways from PBL. The mechanism for the modification occurring in the IHL population during liver regeneration and its biological significance are discussed.
 ...
PMID:[The kinetic changes in murine lymphocyte subsets in regenerating liver]. 157 19

C57BL/Ka bone marrow and spleen cells fractionated by density gradients were transplanted to lethally irradiated (800 rad) BALB/c recipients. Unfractionated bone marrow and spleen cell mixtures (1:1), or high density fractions of these cells induced acute lethal graft-vs-host disease (GVHD). In contrast, low and middle density fractions of bone marrow and spleen cell mixtures reconstituted the irradiated hosts, and the majority survived for at least 100 days. The latter cells contained sufficient hemopoietic cells for reconstitution, but were deficient in inducing GVHD. Examination of the T cell subsets in the low density fractions showed a reduction of typical alpha beta TCR+ CD4+ or CD8+ cells and little change in the proportion of alpha beta TCR+ CD4- CD8- cells. BALB/c mice injected with the BCL1 B cell leukemia/lymphoma were lethally irradiated and transplanted with unfractionated BALB/c or C57BL/Ka bone marrow and spleen mixtures or low density fractions of C57BL/Ka mixtures. All control unirradiated BALB/c mice given the BCL1 tumor cells died by day 55. Almost all BALB/c mice given the BCL1 tumor cells, irradiation, and injected with a syngeneic marrow and spleen mixture died by day 95. All of the latter recipients tested showed evidence of tumor relapse. Almost all BALB/c mice given BCL1 cells, irradiation, and a C57BL/Ka unfractionated marrow and spleen mixture died by day 40. The survival of BALB/c mice given BCL1 cells, irradiation, and a low density fraction of the C57BL/Ka mixture was markedly prolonged as compared to those recipients given unfractionated allogeneic or syngeneic mixtures. None of the low density fraction recipients tested showed evidence of tumor relapse. Similar results were obtained with leukemic C57BL/Ka x BALB/c F1 hybrid mice. Thus, the low density fraction fails to induce acute lethal GVHD, but retains graft-vs-leukemia activity.
 ...
PMID:Treatment of BCL1 leukemia by transplantation of low density fractions of allogeneic bone marrow and spleen cells. 157 52

We developed a syngeneic mouse IgG2a monoclonal antibody (MAb) A9D41 directed against the Friend leukemia virus envelope gp70 antigen present on the cell surface membranes of virus producer 3C18 Friend leukemia cells (FLC). A9D41 showed a marked antitumor activity in DBA/2 mice given injections of gp70 positive 3C18 FLC, but it was ineffective in mice given injections of gp70 negative 745 FLC or unrelated tumor cells. A9D41 was particularly effective in inhibiting the development of 3C18 FLC liver and spleen metastases. MAb was also effective as adjuvant therapy in inhibiting visceral metastases after excision of an established s.c. FLC tumor, and combined therapy of A9D41 with mouse interferon alpha/beta was more effective than MAb or interferon alpha/beta alone. The immune system of the host played a decisive role in the antimetastatic action of A9D41. Thus, although MAb was cytotoxic for 3C18 FLC in vitro in the presence of rabbit complement, the F(ab')2 fragment was ineffective in vivo, and the antitumor effect of MAb was abolished in mice treated with an antibody to CD4 and diminished in natural killer cell-deficient beige and athymic nude mice. MAb-treated mice surviving injection of FLC developed an immune response to 3C18 FLC.
 ...
PMID:Inhibition of Friend leukemia cell visceral metastases by a new monoclonal antibody and role of the immune system of the host in its action. 158 3

Cytotoxic T lymphocyte (CTL) responses to most antigens are generated by in vivo priming and secondary stimulation with antigen in vitro. The present studies were designed to determine whether that strategy could be used to stimulate development of CTL against brain tumors. Rats were primed with one of two tumors, RT2, an astrocytoma, or 9L, a gliosarcoma, and Corynebacterium parvum. Spleen cells from primed rats were stimulated with tumor cells and interleukin-2 in vitro to generate CTL. CTL generated against RT2 killed RT2 and 9L, but not allogeneic or histopathologically unrelated tumor cells, suggesting that the killing was brain tumor-specific and major histocompatibility complex gene product-restricted. Similar results were obtained with rats primed and secondarily stimulated with 9L. Specific cytotoxic cells only developed when syngeneic brain tumor cells were used for both priming and secondary stimulation. The cytotoxic cell populations were composed of OX-19+ T cells with a mixed CD4/CD8 phenotype. Controls consisting of spleen cells from unprimed or primed rats tested before culture exhibited low levels of cytotoxicity against brain tumor targets. Culturing unprimed or primed cells with interleukin-2 alone stimulated cell proliferation, but the cells that grew out exhibited only low levels of cytotoxicity for brain tumor cells. Cell populations exhibited consistent cytotoxicity against natural killer cell targets. None of the cell populations killed lymphokine-activated killer cell targets. The results demonstrated that brain tumor-specific CTL could be produced by priming in vivo followed by secondary stimulation with brain tumor cells in vitro. The results further demonstrated that RT2 and 9L share antigens that both induce and serve as target structures for specific cytotoxic cells.
 ...
PMID:Generation of cytotoxic immune responses against a rat glioma by in vivo priming and secondary in vitro stimulation with tumor cells. 158 47

In previous studies we showed that idiotypic determinants of a B cell hybrid, 2C3, was involved in the generation of idiotype (Id)-specific noncytolytic CD4+ effector T cells that suppressed the Ig expression of wild type 2C3 tumor. In the present investigation we report that Id+ Ig associated with 2C3 was also capable of eliciting syngeneic cytotoxic T lymphocytes (CTL) when mice were hyperimmunized with irradiated 2C3 cells. These effector cells were predominantly Thy 1.2+, CD8+, and CD4- and highly cytotoxic to 2C3 as shown by in vitro and in vivo assays. The unique idiotypic determinants (private Id) of 2C3 Ig was important in the induction of CTL since these effector cells were generated in mice only after immunization with Id+ 2C3 cells. In contrast, immunization of mice with 6B2, an Ig-loss variant of 2C3, and 1BF7, an unrelated syngeneic B cell hybrid which expresses Ig of the same isotype as that of 2C3 but of different Id, failed to elicit any cytotoxic response. Furthermore, incorporation of anti-idiotypic monoclonal and polyclonal antibodies into culture medium abrogated the activation of CTL during in vitro stimulation of the primed splenocytes. Induction of CTL was also inhibited by anti-MHC class I and anti-CD3 monoclonal antibodies, indicating that CD3-TcR complex of the effector T cells were involved in the recognition of Id+ Ig in the context of MHC class I antigens. These results, together with our previous observation, suggest that the anti-2C3 immune response is mediated by two kinds of effector cells, namely, CD4+ noncytolytic and CD8+ cytotoxic T cells. Moreover, the unique private Id associated with 2C3 plays a pivotal role in the induction of both of these effector cells.
 ...
PMID:Induction of syngeneic cytotoxic T lymphocytes against a B cell tumor. I. Role of idiotypic immunoglobulin. 158 59

Monoclonal antibodies and flow cytometry were used to study lymphocyte, monocyte and tumor cell antigen expression in uveal melanoma. Forty-one melanomas were studied after various forms of treatment. An antimelanoma antibody, 13A3E, stained 81.7% of the cells. Tumors treated with helium ions or 125I plaques had 13A3E staining reduced to 62.5%, p = 0.011. HLA-A,B,C stained 85.4%, and HLA-DR stained 7.0% of the cells. T cells (CD3 positive) comprised 4.5% (range 0.1-29.2%) of total cell population. Natural killer (NK) cells, B cells and macrophages were present in small numbers (mean less than 2.5% in each case). Tumors with numerous T cells (greater than 5%), were used for T cell subtype studies. The mean helper/inducer (CD4) to cytotoxic/suppressor (CD8) ratio was 1.00 (range 0.11-3.15). CD8 decreased, and CD4 increased with age in unirradiated tumors (p less than 0.02).
 ...
PMID:Infiltrating lymphocytes and antigen expression in uveal melanoma. 160 88

In this study we describe the generation and characterization of interspecies somatic cell hybrids between human activated mature T cells and mouse BW5147 thymoma cells. A preferential segregation of human chromosomes was observed in the hybrids. Phenotypic analysis of two hybrids and their clones demonstrated coexpression of CD4 and CD69 antigens in the same cells. Segregation analysis of an informative family of hybrids followed by molecular and karyotype studies clearly demonstrated that the locus encoding CD69 antigen mapped to human chromosome 12. Although the expression of CD69 antigen is an early event after T-lymphocyte activation and rapidly declines in absence of exogenous stimuli, in the hybrids described in this study the expression was constitutive, similarly to what was previously found in early thymocyte precursors and mature thymocytes. In this respect it was important to note that the behavior of the hybrids in culture strongly suggested a dominant influence of the thymus-derived mouse tumor cell genome in controlling the constitutive expression of human CD69. These hybrids may thus provide a system to study the genetic and molecular mechanisms controlling the expression and function of this activation antigen.
 ...
PMID:Constitutive expression of CD69 in interspecies T-cell hybrids and locus assignment to human chromosome 12. 161 43

We have studied the cellular immune response that accompanies primary and metastatic brain cancers induced experimentally in rats by inoculation of RG-2 glioma and Walker 256 (W256) carcinoma cells, respectively. The inflammatory cell infiltrates were characterized with lectin histochemistry to visualize microglial cells and macrophages and with immunohistochemistry, using a panel of monoclonal antibodies, to detect major histocompatibility complex (MHC), lymphocytic, and macrophage antigens. The metastatic tumor was composed of a loose stroma with multiple, often large, necrotic areas, whereas the RG-2 glioma was composed of a dense collection of tumor cells showing only rare necrotic foci. Both tumor types were heavily infiltrated with microglia and/or macrophages, and these were positive for MHC Class II (Ia) antigens. Expression of MHC Class I antigens was absent from RG-2 glioma cells, but it was present in W256 metastatic carcinoma cells. The metastatic tumor was also characterized by a much heavier infiltrate of lymphocytes, as shown by the presence of cells positive for CD4, CD8, and leukocyte common antigens. These lymphocytic markers were absent from reactive microglia in the W256 carcinoma, whereas they were present in the RG-2 glioma. Polymorphonuclear leukocytes were seen only in the metastatic tumor. Our study delineates differences between the inflammatory cell infiltrates found in metastatic brain tumors and those found in primary brain tumors. The differences in cell composition and immunophenotype may indicate a more effective antitumor response in the metastatic tumor that could account for the observed tissue destruction.
 ...
PMID:Inflammatory cell infiltrates vary in experimental primary and metastatic brain tumors. 161 93


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