Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Suspensions of fresh tumor-infiltrating lymphocytes (TIL) were prepared from 30 human breast ductal adenocarcinomas. To evaluate the phenotypic pattern of the isolated TIL, lymphocyte surface markers including CD19, CD3, CD4, CD8, CD16 and HLA-DR were examined by flow cytometry. Lymphocyte recovery ranged from 1.1% to 44%, independent of tumor size. TIL most often scored high for CD3+ with a varying number of CD4+ and CD8+ cells. Three samples out of 30 expressed up to 44% of CD19+ B cells, while CD3-CD16+ NK cells were rare. CD4 and CD8 expression was significantly different between the lymph node metastases group and the lymph node negative group (p < 0.01). 67% of the TIL with a CD4/CD8 ratio greater than 1 showed lymph node metastases. Furthermore, the CD4 expression of TIL and CD4/CD8 ratio correlated with tumor size (p < 0.01), but not with tumor differentiation and hormone receptor expression. Although there was considerable diversity of TIL among breast tumors, our data suggest that a high expression of CD4+ T cells may imply progression of the tumor, and an increased CD4/CD8 ratio of the TIL isolated from human breast adenocarcinoma may indicate development of metastases.
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PMID:Phenotypic analysis of tumor-infiltrating lymphocytes from human breast cancer. 133 79

In vitro models of intestinal cell differentiation provide an important adjunct for studying normal and abnormal intestinal epithelial cell differentiation. The studies reported herein describe morphologic and biochemical changes in the colonic epithelial cell line SW620 following dimethylsulfoxide (DMSO) incubation. Cells cultured in the presence of DMSO showed striking changes in morphology characterized by enlargement, elongation, and formation of process-like structures by light microscopy and a propensity to form microvillus-like structures by electron microscopy. These changes were accompanied by significant differences in the expression of the cell surface markers CD4 (HIV gp120 receptor), CD44 (hyaluronate receptor), and KS1 (adenocarcinoma/epithelial specific antigen). There was a marked decrease in CD4 expression (38% to 2%), an increase in CD44 expression (4% to 50%) and a decrease in KS1 expression (98% to 66%) as detected by flow cytometry following incubation of SW620 cells in DMSO. Parallel changes in the expression of these markers were seen by metabolic and surface labeling studies. Although SW620 cells were infected by HIV-1, DMSO-treated SW620 cells could not be infected. DMSO-induced changes in surface expression of CD4, CD44, and KS-1 were reversible over time upon removal of DMSO from the culture medium. Secretory component, sucrase, neuron-specific enolase, chromogranin-A, and mucin were not detectable in SW620 cells with or without DMSO treatment. SW620 cells provide a useful model for studying specific biochemical and molecular events involved in intestinal epithelial cell differentiation and function.
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PMID:Biochemical and morphological differentiation of the human colonic epithelial cell line SW620 in the presence of dimethylsulfoxide. 140 Jun 16

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

Tumor-associated lymphocytes (TAL) were isolated from the ascitic fluid of patients with adenocarcinoma of the ovary. These cells proliferated and expanded by 100-600-fold as either CD3+ CD4+ or CD3+ CD8+ cultures in the presence of moderate concentrations (50-200 cetus units/ml) of recombinant interleukin 2 and reached high numbers (5 x 10(8)-1 x 10(9)). After expansion of 16 TAL samples from 15 patients, 5 of the 7 isolated ovarian cytotoxic T-lymphocyte cell lines of T-cell receptor (TCR) (alpha beta)+ CD3+ CD8+ CD4- phenotype exhibited preferential cytolytic activity against autologous tumor targets and significantly lower cytolytic activity against allogeneic tumor targets and the natural killer-sensitive cell line K562. The cytolytic activity of the CD8+ TAL was inhibited by operationally anti-TCR (alpha beta) monoclonal antibody and monoclonal antibody specific for the CD3 differentiation antigen, indicating that the TCR and CD3 are involved in the cytolytic process. The other TAL cultures demonstrated similar cytolytic activity against both autologous and allogeneic tumors. The phenotype of these TAL was predominantly TCR (alpha beta)+ CD3+ CD4+ CD8-. Certain CD3+ CD8+ T-cell clones isolated from representative TAL exhibited preferential autologous tumor-specific cytotoxicity that may be major histocompatibility complex restricted. Other CD3+ CD8+ and CD3+ CD4+ clones exhibited nonmajor histocompatibility complex restricted cytotoxicity. These results demonstrate that CD3+ CD4+ and CD3+ CD8+ T-cells present in the ovarian malignant ascites can be propagated in large numbers and for long time intervals as T-cell lines in vitro. This finding may be significant for further investigation of ovarian tumor-specific cytotoxic T-lymphocytes and future adoptive specific immunotherapy studies.
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PMID:Tumor cytolysis by lymphocytes infiltrating ovarian malignant ascites. 186 46

This study was undertaken to investigate the effects of a single infusion of radiolabelled murine monoclonal antibody (MAb) on peripheral blood leukocytes in cancer patients. Eleven patients with disseminated colon cancer, malignant melanoma, or lung adenocarcinoma were infused with 111In-labelled anti-ZCE 025, anti-p97 type 96.5c, or LA 20207 MAb, respectively. Blood samples were obtained before infusion, immediately after infusion (1 hr), and at 4 and 7 days postinfusion. Flow cytometry analysis of CD3+, CD4+, CD8+, CD16+, and CD19+ lymphocytes showed increasing CD4:CD8 ratios in seven patients after infusion. This phenomenon was not restricted to antibody subclass or to type of cancer. Two of the remaining patients exhibited a marked post-infusion increase in CD8+ cells. In all three patients with malignant melanoma, decreasing levels of CD16+ lymphocytes were noted after infusion and natural killer cell cytotoxicity showed fluctuations which paralleled the changes in the CD16+ subpopulation. Oxygen radical production by phagocytic cells was markedly affected in three subjects. These results suggest that a single infusion of radiolabelled murine MAb may alter the balance of critical lymphocyte subpopulations and modulate other leukocyte responses in cancer patients.
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PMID:Effects of radiolabelled monoclonal antibody infusion on blood leukocytes in cancer patients. 196 68

The ability of rIL-4 to trigger host reactivity against both a chemically induced fibrosarcoma (CE-2) and a spontaneous adenocarcinoma (TS/A) of BALB/c mice was studied. Daily local s.c. administration around tumor draining lymph nodes of 10 injections of progressive amounts (0.00001 to 1000 pg/day) of rIL-4 induced appreciable inhibition of the growth of both tumors after a dose-response survival curve peaking at 0.1 pg/day. Inasmuch as rIL-4 has no direct antitumor activity, as shown by in vitro tests, host immune reactivity plays a fundamental role in this lymphokine activated tumor inhibition (LATI). LATI, in fact, is abolished when recipient mice are sublethally irradiated or treated with cyclosporin A, or when the reactivity of CD4+ lymphocytes is suppressed, whereas it is not affected by anti-asialo GM1 antibody. The morphologic data show that rIL-4 LATI rests on the recruitment of several cell reaction mechanisms, among which those that are nonspecific seem to predominate. rIL-4 LATI also leads to a state of long lasting and specific immune memory: the growth of a second contralateral tumor challenge is significantly impaired after LATI. This immune memory takes place after LATI of both the poorly immunogenic CE-2 fibrosarcoma and the TS/A adenocarcinoma, previously classed as nonimmunogenic on the basis of immunization-protection tests. In the latter case, adoptive transfer experiments show that Thy-1+ lymphocytes and, in particular, the CD4 cell-depleted T lymphocyte subpopulation, are responsible for the immune memory. Finally, the ability of rIL-4 to trigger LATI is greater than that of the most effective doses of rIL-2, rIL-1 beta, and IFN-gamma, whereas its association with rIL-1 beta induces a more effective immune memory.
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PMID:Low doses of IL-4 injected perilymphatically in tumor-bearing mice inhibit the growth of poorly and apparently nonimmunogenic tumors and induce a tumor-specific immune memory. 221 77

The CD4 glycoprotein serves as a receptor for the human immunodeficiency virus HIV, the etiologic agent of acquired immunodeficiency syndrome (AIDS). We have examined the expression of CD4 molecules in a clone (HT29-D4) derived from a human colon adenocarcinoma cell line. HT29-D4 cells synthesized a 60 kDa polypeptide immunoprecipitated with two anti-CD4 monoclonal antibodies after metabolic or cell surface labeling. This 60 kDa polypeptide was also immunodetected using the same antibodies in human acute lymphoblastic leukemia cells CEM which are known to express CD4. HT29-D4 cells can be induced to differentiate into enterocyte-like cells by removing glucose from the culture medium. Under these conditions, HT29-D4 cells form a polarized epithelial monolayer in which tight junctions separate the plasma membrane in an apical and a basolateral domain. The localization of CD4 molecules in differentiated HT29-D4 cells was exclusively restricted to the basolateral membrane domain as demonstrated by radioimmunoassay and indirect immunofluorescence studies. Therefore the HT29-D4 clonal cell line represents a unique model for polarized HIV infection of colonic epithelial cells and may be useful to understand some of the gastrointestinal disorders occurring in AIDS patients.
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PMID:CD4 molecules are restricted to the basolateral membrane domain of in vitro differentiated human colon cancer cells (HT29-D4). 236 56

The phenotype of glass-adherence-depleted tumor-immune peritoneal exudate lymphocytes (PEL) which generated anti-tumor reactivity against the rat mammary adenocarcinoma 13762A in vitro was examined by indirect panning. Monoclonal antibodies W3/25 and OX8, directed against the CD4 and CD8 differentiation antigens, respectively, were used to separate immune PEL into subsets of functionally different T cells. The panned populations of immune PEL were examined for anti-tumor reactivity in three different in vitro assays. Tumor-specific proliferation, tumor-specific induction of the helper lymphokine interleukin 2 (IL-2), and tumor-specific induction of an antiproliferative tumor-induced suppressor lymphokine (TISL) were determined. Panning experiments together with indirect immunofluorescence analysis of unpanned immune PEL indirectly indicated that a proportion of cells (15-20%) coexpressed CD4 and CD8 antigens. Strong tumor-specific proliferation and IL-2 and TISL production were generated from these double-positive cells, as determined by double-panning experiments. Significant tumor-specific proliferation and IL-2 production were produced also from CD4+CD8- cells, but TISL production was minimal, and could be accounted for by contaminating CD4+CD8+ cells. CD4-CD8+ cells produced negligible responses against the tumors as measured by these three assays, and no synergistic responses were demonstrated when CD4-CD8+ cells were incubated together with CD4+CD8- cells. These data demonstrated that CD4+CD8+ T cells exist in primed populations of rat peripheral lymphocytes, and that both helper and suppressor functions were generated from these double-positive cells.
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PMID:Helper and suppressor functions of panned populations of immune peritoneal T cells with reactivity to the rat mammary adenocarcinoma 13762A. 244 78

We report the presence of a CD4-mediated T-cell activation pathway on an autoreactive CD3+WT31+CD4+CD8- T-cell clone, designated 2F9, isolated from the peripheral blood of a patient with ovarian adenocarcinoma. The OKT4 mab modulated the CD4 antigen independently of the CD3 antigen or the alpha beta T-cell receptor. OKT4 mab immobilized on plastic or soluble OKT4 mab in the presence of feeder PBMC induced proliferation and IL-2 production by cells of the 2F9 clone. Mixtures of the OKT4 mab and the OKT3 or anti-WT31 mabs induced additive proliferative responses and IL-2 production. The OKT4 mab synergized with recombinant IL-2 in inducing proliferative responses. These results suggest the presence of activation pathway on 2F9 cells.
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PMID:OKT4 monoclonal antibody-induced activation of an autoreactive T-cell clone. 257 Jun 45

A 67-year-old man was admitted in October 1987 with complaints of nausea, headache, dizziness and speech disturbance. Hematological examination showed pancytopenia. Bone marrow aspiration failed with a dry tap. A month later, the second aspiration showed hypocellular marrow containing 18.2% of lymphoma cells. Physical examination showed splenomegaly and lymph node swelling. Polyclonal hypergammaglobulinemia was not observed. A lymph node biopsy exhibited typical histology of immunoblastic lymphadenopathy (IBL)-like T cell lymphoma. Surface marker CD3 and CD4 positive cells were dominant. The patient complained of epigastric pain and occult blood was positive in stool. Gastrofiberscopic examination disclosed well differentiated adenocarcinoma in situ located on a polyp, and polypectomy was performed. Lymphoma was treated with cyclophosphamide, doxorubicin, vinblastine and prednisolone. Splenomegaly and lymph node swelling were reduced in size but the effect was temporary. Thereafter the patient has been treated with cyclophosphamide, doxorubicin, vindesine, prednisolone and etoposide every 3 weeks. This is our first case report of IBL-like T cell lymphoma associated with early gastric cancer.
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PMID:[IBL-like T cell lymphoma associated with early gastric cancer: a case report]. 278 12


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