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

Peripheral blood lymphocytes (PBL) of gastric cancer patients in advanced stages showed lymphokine activated killer (LAK) activities comparable to those of healthy donors, suggesting potential applicability of LAK cells induced from PBL stimulated with recombinant interleukin-2 (rIL-2) in adoptive immunotherapy (AIT) for gastric cancer. In order to generate a large number of LAK cells from PBL, lymphocytes were cultured with both rIL-2 and phytohemagglutinin (PHA). In this culture, the numbers of cells increased to a greater extent than those in culture with rIL-2 alone but cytotoxic activity did not augment, thus suggesting that this procedure would not afford sufficient clinical effects. On the other hand, a large number of LAK cells with high anti-tumor activities were efficiently induced from spleen cells of the patients by culture of rIL-2; hence clinical usefulness of these LAK cells is anticipated. In regional lymph node lymphocytes (RLNL) cultured with rIL-2, the cytotoxic activities were lower than in those induced in PBL, and a characteristic increase of CD8 + CD11 + suppressor T cells was observed after incubation with rIL-2. Nevertheless, an increase of CD4 + 4B4 + helper inducer T cells was also observed in RLNL after the culture with rIL-2. Furthermore, high cytotoxic activities were induced in RLNL in some cases in which metastasis to the regional lymph nodes was not detected. When gastric cancer patients were pretreated with biological response modifiers (BRM), especially with Lentinan, LAK cells from PBL showed higher NK and LAK activities as compared with those of patients without BRM pretreatment.
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PMID:Evaluation of basic procedures for adoptive immunotherapy for gastric cancer. 152 56

Nineteen patients with metastatic liver tumor (9 of gastric cancer, 5 of colon cancer, 2 of pancreatic cancer, one each of mammary cancer, cholecystic cancer, carcinoid of biliary tract) and one patient with primary liver cancer were treated by endogenously induced LAK therapy consisting of transhepatic arterial infusion with ADM or MMC for induction therapy and OK-432 and rIL-2 (TGP-3) for immunotherapy. The following results were obtained. 1) Clinical response for liver tumor showed no CR but 8 cases of PR, for an overall response rate of 42.1%. 2) Reduced tumor marker value was noted in 76.5% cases, and 50% survival term became 349 days after the therapy. 3) Many CD4 and CD8 positive mononuclear cells had infiltrated around liver tumor after therapy by immuno-histochemical staining of surface marker. 4) NK activity of peripheral blood lymphocytes was markedly reduced soon after the therapy and continued for about 4-7 days, while in cases of combined subcutaneous administration with OK-432, NK activity showed only a slight decrease.
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PMID:[Significance of antitumor effects and immunological response on endogenously induced LAK therapy for primary or metastatic liver tumor]. 153 Feb 92

Little is known about the role of tumor infiltrating T lymphocytes (TIL-T) in the pathogenesis of malignant diseases and collaboration between normal and malignant cells has not yet been proved. In the present work, we have investigated whether immune T lymphocytes exist in tumors invaded by B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). Therefore, we have studied the reactivity of the CD45RA monoclonal antibody, which discriminates between naive and memory CD4 T lymphocytes. Our results showed far lower percentages of CD4+ CD45RA+ in malignant lymphoma (30.3 +/- 15.0% in B-cell NHL, and 37.4 +/- 18.6% in HD) than in reactive hyperplasia (54.7 +/- 13.2%), leading to the conclusion of an accumulation of immune cells in tumor microenvironment. A further heterogeneity in the relative proportion of naive and memory TIL-T was also observed within lymphoma (range: 11 to 68% in B-cell NHL, 5 to 69% in HD). In B-cell NHL, it was related to histological features, as documented by the Kiel classification (P = .028), and to a stronger extent to cytological characteristics analysed with the Grenoble classification (P less than .0001): class 1 NHL, which are essentially indolent NHL displayed lower naive cells (22.2 +/- 7.4%) than class 3 NHL, which are more aggressive (40.1 +/- 16.1%). Among the monoclonal antibodies (mAb) defining the B-cell clone phenotype or activation state (CD19, CD20, CD21, CD22, CD23, CD24, CD5, CD10, CD11a, and Ki67), only CD23 (P = .0003) and Ki67 (P = .0007) revealed statistical association with the percentage of naive CD4 lymphocytes. No correlation could be demonstrated with the proportion of whole TIL-T, activated CD3 DR TIL-T, or CD4 subset.
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PMID:CD45RA expression by CD4 T lymphocytes in tumors invaded by B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). 153 69

Coculture of purified murine T cells with anti-CD3 monoclonal antibody (145-2C11) results in the induction of nonspecific cytotoxic T lymphocytes (CTL) with MHC-unrestricted cytolytic activity against a range of tumor targets. Serine proteases associated with effector cell granules are among the molecules postulated to play a role in cell-mediated cytolysis. The present study examines the ability of exogenous serine protease substrates to inhibit anti-CD3-activated cytotoxic T (ACT) cell-mediated killing of P815 mastocytoma and YAC1.2 lymphoma target cells. The chymotrypsin substrate N-acetyl-L-tyrosine ethyl ester (ATEE) was found to significantly inhibit ACT cell-mediated cytolysis. In contrast, the trypsin substrate N-benzoyl-L-arginine ethyl ester (BAEE) had little, if any, effect on ACT cell-mediated cytolysis. These effects were observed with both target cell populations. Conjugate inhibition studies performed with ATEE indicated that a chymotrypsin-like serine protease is involved in a postbinding event during cytolysis. Pretreatment of either target or effector cells with ATEE prior to cytolytic assay revealed that the chymotrypsin-like serine protease involved in cytotoxicity is of effector cell origin. Northern blot analysis of total RNA extracted from ACT cells revealed the presence of transcripts coding for CCP1 and CCP2 serine proteases known to be involved in antigen-specific CTL function, but little or no expression of the HF serine protease which has also been implicated in antigen-specific CTL killing. CCP2 exhibits chymotrypsin-like activity while HF displays trypsin-like activity. On the other hand, the CCP1 gene product has protease activity which resembles neither chymase nor tryptase activities. Thus, the level of mRNA expression for these serine proteases is consistent with our earlier observations, using the serine protease substrates, that a chymotrypsin-like serine protease but not a trypsin-like serine protease is involved in ACT cell-mediated cytolysis. "Lymphocyte panning" of ACT cells revealed abundant CCP1 and moderate CCP2 mRNA expression in CD4- and CD8+ anti-CD3-activated T cells with strong tumoricidal activity. CD8- anti-CD3-activated T cells with moderate cytolytic activity also expressed substantial levels of CCP1 and CCP2 mRNA, suggesting that both CD4- CD8- and CD4- CD8+ ACT cells participate in killing tumor targets. In contrast, CD4+ anti-CD3-activated T cells lacked both cytolytic activity and significant CCP1 and CCP2 mRNA expression. These findings are consistent with the involvement of chymotrypsin-like, as well as other, serine proteases in CTL-mediated lysis.
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PMID:Expression and utilization of chymotrypsin-like but not trypsin-like serine protease enzymes by nonspecific T killer cells activated by anti-CD3 monoclonal antibody. 153 39

Tumor-infiltrating lymphocytes (TIL) were obtained from a mouse melanoma cell line (CL 62) transfected with the gene for the human melanoma Ag p97. TIL were cultured with anti-CD3 antibody and IL-2 for up to 38 days. Flow cytometry identified these TIL as Thy-1.2 + ve/CD4-ve/CD8 + ve cells. A heteroconjugated antibody 500A2 x 96.5, specific for both the CD3 Ag on TIL and the p97 Ag on CL 62 melanoma cells, was prepared using N-succinimidyl-3-(2-pyridyldithio)-propionate as a linking agent. TIL alone demonstrated low levels of cytotoxicity against autologous CL 62 tumor and also against the parental K1735 tumor and an allogeneic murine melanoma (B16). The addition of 500A2 x 96.5 heteroconjugated antibody enhanced TIL-mediated lysis of CL 62 tumor, but not of the K1735 or B16 tumors. This enhanced cytotoxicity was elicited at E:T ratios as low as 0.4:1, and in TIL cultured for 7 to 38 days. These results suggest that hetero-conjugated antibody may enhance the anti-tumor effect of TIL in vivo.
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PMID:Enhancement of in vitro tumor-infiltrating lymphocyte cytotoxicity by heteroconjugated antibodies. 153 18

We have recently reported that autologous tumor-specific cytotoxic T lymphocyte (CTL) lines and clones can be developed from lymphocytes infiltrating ovarian malignant ascites (TAL). In this study, we investigated the biological effects of tumor necrosis factor alpha (TNF alpha) in the induction, expansion, long-term proliferation and lytic function of CD8+ TAL. TNF alpha up-regulated the IL-2 receptor (IL-2R) alpha chain (Tac antigen) on the surface of CD3+ CD8+ CD4- TAL, enhanced the proliferation of autologous tumor-specific CTL, and potentiated their lytic function in long-term cultures. Furthermore, in the induction and expansion phase of CD8+ TAL, the presence of TNF alpha was associated with a selective increase in CD8+ IL-2R+ (Tac+) cells, and subsequent decrease in CD4+ IL-2R+ (Tac+) cells. These results suggest that the observed facilitation of the outgrowth of CD8+ cells in TAL cultures may be due, at least in part, to the up-regulation of IL-2R, and indicate the usefulness of TNF alpha in the analysis of signalling in autologous tumor-reactive CTL.
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PMID:Induction of interleukin-2 receptor by tumor necrosis factor alpha on cultured ovarian tumor-associated lymphocytes. 153 15

Plasmacytoid T-cell (PTC) lymphoma is a rare clinicopathologic entity characterized by generalized lymphadenopathy in association with a myeloproliferative disorder. Hepatosplenomegaly and weight loss frequently are present. Nodal T-zone expansion by mononuclear cells with ultrastructural and immunohistochemical features typical of PTC is diagnostic. All of the five previously reported cases of PTC lymphoma coincided with or heralded the onset of a clinically aggressive myeloid leukemia. This strong association and recent immunohistochemical findings in reactive or neoplastic PTC favored a monocyte/macrophage derivation of these cells, and it has been suggested that they be renamed plasmacytoid monocytes (PM). Two additional cases of PTC lymphoma were studied at the institutions of the authors, and the findings supported the concept that PTC belong to the monocytic lineage. The disease presentation was generalized lymphadenopathy with constitutional symptoms. One patient also had hepatosplenomegaly and bilateral renal enlargement concomitantly with myelofibrosis with myeloid metaplasia that progressed within months to acute myelogenous leukemia. Similar rapid evolution of acute monoblastic leukemia occurred in the other patient. Tumor cells within subtotally effaced lymph nodes had positive findings for CD45, CD4, CD7, and LN2 and negative findings for CD3, CD8, and beta F1. Occasional cells had positive findings for CD2. One case demonstrated CD5, HLA-DR, CD71, and CD43 (Leu-22)-positive cells. The myeloid/monocyte-associated antigens CD14 and CD68 were identified in both. The tumor cells lacked the B-cell markers LN1, CD20 (L26), CD19, and CD22 and did not rearrange immunoglobulin heavy chain genes and T-cell receptor beta, gamma, and delta chain genes. The term plasmacytoid T-zone lymphoma or PM proliferation is more appropriate for this rare disease. The close association of the PM proliferation with a myeloproliferative disorder indicates that the two entities are related.
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PMID:Plasmacytoid monocyte proliferation associated with myeloproliferative disorders. 154 Aug 83

Lymphocytes have a finite and predictable proliferative life span in culture similar to that observed in fibroblasts. In general, the senescence of human fibroblasts is inevitable and irreversible, but their proliferative life span can be extended by certain DNA tumor virus oncogenes, such as the large T antigen of the SV40 virus. Here, we show that human T lymphocytes (HTL) can be stably transfected with SV40 large T and that expression of T antigen extended the life span of T cell cultures. PHA-stimulated HTL were transfected with pSV3neo, an expression vector containing the SV40 early region and the neomycin resistance gene. Transfectants were selected for neomycin (G418) resistance. Control HTL, either mock transfected or transfected with pSV2neo (containing the neomycin resistance gene only), ceased proliferation after about 17 population doublings. In contrast, HTL transfected with pSV3neo underwent more than 170 doublings. pSV3neo-transfected cells expressed SV40 large T RNA, detectable by in situ hybridization, and SV40 T antigen, detectable by immunofluorescence. Greater than 95% of the transfected cells were CD4 positive. These results clearly show that SV40 large T enables HTL to escape senescence. Transfection with SV40 large T may be a valuable method for obtaining long term human T cell lines for studies of both aging and immunology.
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PMID:Extension of lifespan of human T lymphocytes by transfection with SV40 large T antigen. 154 79

The cutaneous T-cell lymphomas (CTCL) are a group of diseases characterized by malignant proliferations of CD4 positive T-cells having monoclonally rearranged T-cell receptor (TCR) genes. A recent study using monoclonal antibodies to two TCR beta-chain variable (V) region gene products showed preferential expression of the V beta 8 gene product in these tumors. The finding of predominant usage of a single V beta gene would imply that selection by antigen is important in the etiology of these tumors. We have studied eight cases of cutaneous T-cell lymphoma and one cell line derived from a patient with mycosis fungoides/Sezary syndrome, using an extended panel of antibodies to V region gene products. Contrary to the previous report, in our study expression of the V beta 8 gene product by tumor cells was not observed in any of the cases of CTCL or in the tumor cell line studied; preferential use of any of the variable region genes recognized by the antibodies in the panel was not observed.
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PMID:T-cell receptor variable region gene expression in cutaneous T-cell lymphomas. 155 63

Quantitative evaluation of the levels of endogenous gamma-interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the extracts of tumor, peritumoral and normal colorectal tissues resected surgically from 43 patients with colorectal adenocarcinoma was carried out using solid-phase, sandwich radioimmunoassay (RIA). The levels of both IFN-gamma and TNF-alpha detected in the tumor tissues were higher than those in the peritumoral and normal tissues obtained from each patient. A significant negative correlation was observed between the levels of IFN-gamma and TNF-alpha in each tumor tissue. The decrease of endogenous IFN-gamma in the tumors correlated with the advance of histopathological stages. Thirty seven patients were classified into three types according to the endogenous IFN-gamma distribution (intratumoral dominant type, peritumoral dominant type and nonreactive type). There was no significant difference concerning to the tumor diameters among them. However, the mean stage of the intratumoral dominant type was significantly earlier than that of the nonreactive types. On the other hand, the increase of endogenous TNF-alpha correlated with the maximum diameter of primary tumors. The production of endogenous TNF-alpha was localized in the tumor tissues, and the significant elevation of endogenous TNF-alpha was not observed in the peritumoral tissues. The immunohistochemical staining of IFN-gamma- and TNF-alpha-producing cells in tumor tissues represented that IFN-gamma was mainly produced by CD4+CD8-CD11c- lymphocytes and that TNF-alpha was mainly produced by CD4-CD8-CD11c+ cells with macrophage-like morphology. These results suggest that CD4+ lymphocytes producing IFN-gamma might play an important role in the anti-tumor response against cancer progression in human colorectal adenocarcinoma.
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PMID:[Detection of endogenous IFN-gamma and TNF-alpha in tumor-infiltrating mononuclear cells of human colorectal cancer]. 155 60


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