Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Freshly isolated cells from patients with pleural or peritoneal effusions cytologically diagnosed as adenocarcinoma (n = 43), malignant nonepithelial neoplasms (n = 10), and benign (n = 8) were analyzed for expression of constitutive levels of the tumor antigens TAG-72 [recognized by monoclonal antibody (MAb) B72.3] and carcinoembryonic antigen (CEA) (recognized by MAb COL-4) as well as the class I and class II major histocompatibility (MHC) antigens, and the ability of human interferons (Hu-IFNs) to enhance cell surface expression of those antigens as measured by MAb binding. Both type I and type II IFNs enhanced the expression of TAG-72 and CEA and altered the level of expression of the MHC antigens. Comparative studies of three different Hu-IFNs (IFN-alpha A, IFN-beta ser, and IFN-gamma) revealed that IFN-gamma was the most potent in augmenting either B72.3 or COL-4 binding. Unlike the IFN-gamma -mediated induction of the class II human leukocyte antigens, the change in tumor antigen expression consisted of enhanced constitutive antigen expression; de novo induction of either TAG-72 or CEA could not be achieved by either type I or type II IFN. Of 43 effusions isolated from different adenocarcinoma patients, 42 (97.7%) expressed either CEA or TAG-72, and treatment with Hu-IFN increased the level of expression of either antigen in 36 of 42 samples (85.7%). These studies demonstrate the augmentation of tumor-associated antigens on human carcinoma cells isolated from serous effusions by Hu-IFNs which may be used to enhance the targeting of conjugated MAbs to human carcinoma lesions.
 ...
PMID:Selective interferon-induced enhancement of tumor-associated antigens on a spectrum of freshly isolated human adenocarcinoma cells. 246 27

A synergistic increase in the cytotoxic effects of recombinant human tumor necrosis factor (TNF-alpha), interferons (IFN-alpha, IFN-beta, and IFN-gamma) and heat-stress was demonstrated in vitro. The toxicity of these agents was assessed in the human cervical carcinoma HeLa cell line: the toxic effect was greatly increased when cells pretreated with IFNs or TNF were submitted to a 1-h heat-shock at 45 degrees C. Moreover if the heat-stress followed simultaneous treatment with both cytokines, a synergistic effect between these treatments could be observed. The same observations were made for two other transformed cell lines: the oral epidermoid carcinoma KB cells and the hepatocarcinoma PLC/PRF/5 cells. In contrast, the survival of normal cells (normal foetal lung MRC5 cells and foreskin F 7000 fibroblasts) was only slightly decreased by such treatments. These results suggest that combining a heat-stress with cytokines treatment might be one way of enhancing the sensitivity of cancer cells to the growth inhibitory effects of the individual cytokines.
 ...
PMID:Synergistic cytotoxic effects of recombinant human tumor necrosis factor, interferons, and heat-stress. 247 47

The purpose of these studies was to determine the possible mechanisms responsible for the therapeutic effects of systemic administration of 5-fluorouracil (FUra) and gamma-interferon on disseminated human colon cancer. We used several human carcinoma cell lines that were established from different surgical specimens. Some lines were selected in nude mice for increased metastatic potential, and one line was selected in vitro for resistance to human recombinant gamma-interferon (r-IFN-gamma). In initial in vitro studies, FUra was cytostatic against all the human cell lines but did not produce cytolysis in any of the lines tested. The two r-IFN-gamma were species specific for both antitumor and immunomodulatory effects. Human r-IFN-gamma produced cytostatic and cytolytic effects against sensitive human colon carcinoma cells but did not activate tumoricidal properties in mouse macrophages. In contrast, mouse r-IFN-gamma had no direct cytotoxic effects against any of the human colon carcinoma lines but did activate tumoricidal properties in mouse macrophages. Human colon carcinoma cells (sensitive or resistant to human r-IFN-gamma) were implanted into the spleens of nude mice. Three days later, we began treatments with FUra and human or mouse r-IFN-gamma. In all experiments, the combination of FUra with mouse r-IFN-gamma produced the best therapeutic effects against growth of the cells in the spleen and in the liver. Because the mouse r-IFN-gamma is devoid of direct antitumor effects (against human tumor cells) but is a potent macrophage activator, these results suggest that the antitumor effects were due to direct antitumor effects of FUra and to activation of host defense mechanisms by the r-IFN-gamma.
 ...
PMID:Mechanisms of combined effects of gamma-interferon and 5-fluorouracil on human colon cancers implanted into nude mice. 249 6

Lymphokine-activated killer (LAK) cells are cytotoxic for a variety of autologous and allogeneic tumor cells as well as modified autologous cells. It is assumed that LAK cells lyse their targets solely by direct cell to cell contact, possibly involving the degranulation and exocytosis of pore-forming elements, similar to that observed with cytotoxic T lymphocytes and NK cells. Reported here are studies demonstrating that LAK cells release factor(s) that are cytotoxic for a human breast carcinoma cell line, MCF-7, when stimulated with tumor cells. The factor(s) are slow acting and maximum cytotoxicity is observed only in a 72-h cytotoxic assay. The ability of LAK cells to secrete cytotoxic factor(s) is dependent on both the ratio of LAK cells to stimulating tumor cells as well as the length of their coincubation. A number of similarly slow acting cytokines that are cytostatic and/or cytotoxic for tumor cells have been described. We tested the ability of specific polyclonal antibodies directed against TNF, IFN-alpha, IFN-beta, and IFN-gamma to neutralize the cytotoxic supernatant activity. Only antibodies specific for IFN-gamma and TNF were neutralizing. We measured the amounts of IFN-gamma and TNF in the cytotoxic supernatants and determined that increased amounts of IFN-gamma and TNF were released after LAK cell-tumor cell interactions compared to supernatants of LAK cells alone or tumor cell alone. Comparable concentrations of human rIFN-gamma and rTNF resulted in similar levels (50 to 90%) of MCF-7 cell cytotoxicity as those observed with the stimulated LAK cell supernatants. We thus concluded that the majority of the cytotoxic activity released by LAK cells when stimulated with tumor cells was attributed to the synergistic activities of IFN-gamma and TNF. The significance of these observations in relation to the possible mechanisms by which LAK cells mediate cytolysis is discussed.
 ...
PMID:Tumor targets stimulate IL-2 activated killer cells to produce interferon-gamma and tumor necrosis factor. 249 6

Sensitivity of cultured choriocarcinoma cell lines to tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma was examined and compared with that of other cultured tumor cell lines. Tumor cells were cultured with 1,000 mu/ml of TNF-alpha and/or 100 mu/ml of IFN-gamma for 24hr. Antitumor effects of the lymphokines were measured by 3H-thymidine uptake and tetrazolium salt (MTT) colorimetric assay. The results revealed that TNF-alpha and/or IFN-gamma had little anti-tumor effect on the choriocarcinoma cell lines tested, while they had cytostatic and cytotoxic effects on other cultured tumor cell lines including Panc-1 (pancreatic carcinoma cell line), Lovo (colon carcinoma cell line) and Ishikawa (uterine endometrial carcinoma cell line). We also examined the effect of TNF-alpha and IFN-gamma on the expression of major histocompatibility complex (MHC) class I antigens in these tumor cell lines by means of cellular binding radioimmunoassay. No enhancing effect was observed on choriocarcinoma cell lines after the treatment with TNF-alpha and/or IFN-gamma. These results suggested the existence of a unique property of choriocarcinoma cells which results in the resistance to host immune attacks.
 ...
PMID:[Low sensitivity of choriocarcinoma cell lines to tumor necrosis factor (TNF)-alpha]. 250 46

In the present study we have evaluated the effect of recombinant interferons, including leukocyte (IFN-alpha A), fibroblast (IFN-beta) and immune (IFN-gamma), and the tumor promoting agent 12-0-tetradecanoyl-phorbol-13-acetate (TPA) on the expression of tumor associated antigens (TAA) and class II HLA-DR antigens on human breast carcinoma cell lines. The effect of these agents on the shedding of a high molecular weight tumor associated glycoprotein, BCA-225, was also determined. All three interferons and TPA enhanced the expression of the Mr 180,000 carcinoembryonic antigen (CEA) and CEA-related TAA recognized by monoclonal antibody B1.1 in both T47D and MCF-7 human breast carcinoma cell lines. The three types of interferons and TPA differed in their absolute TAA-augmenting ability, even in single-cell subclones derived from MCF-7 cells and previously shown to display a differential susceptibility to IFN-alpha augmentation of B1.1 expression. In general, IFN-gamma was more effective than IFN-alpha, IFN-beta or TPA in augmenting the expression of TAA, CEA and BCA-225, and HLA-DR expression in T47D and MCF-7 cells. Differences were also apparent in the ability of the three interferon preparations and TPA to induce shedding of BCA-225 in T47D and MCF-7 cells and their subclones. As observed with TAA expression, IFN-gamma was the most effective preparation in inducing TAA shedding. IFN-gamma also induced the expression and the shedding of BCA-225 by a subclone of T47D cells, T47D cl 17, which normally displays a reduced expression of BCA-225 and does not spontaneously shed this TAA without exposure to IFN-gamma. Recombinant leukocyte interferon (IFN-alpha A) also enhanced BCA-225 expression on T47D cells grown as xenografts in nude mice in vivo. The results of the present study emphasize the complexity of potential antigenic responses which can be induced in human breast carcinoma cells when they are exposed to biological response modulators, including different types of interferon, and tumor promoting agents, such as TPA. This investigation also indicates that both classes of agents can differentially augment expression and/or shedding of TAA by specific breast carcinoma cell lines as well as subclones derived from the same breast carcinoma cell line.
 ...
PMID:Increased surface expression and shedding of tumor associated antigens by human breast carcinoma cells treated with recombinant human interferons or phorbol ester tumor promoters. 251 15

The interferon (IFN) activity of sera from 19 patients with nasopharyngeal carcinoma (NPC) was determined by the plaque-reduction assay with vesicular stomatitis virus (VSV) in HeLa cells and compared to that of sera from matched healthy controls. High titers of interferon were detected in the sera of the NPC patients with a geometric mean titer (GMT) of 43 +/- 25 U/ml. The interferon activity of the patients' sera was acid- and heat-labile (pH = 2 and 56 degrees C for 1 hr) and could be neutralized by a goat antiserum to human IFN-gamma. Interferon titers of the patients, in contrast, to normal controls, were not correlated with natural killer (NK) activity which was abnormally low in the NPC patients. On the other hand, a high percentage of circulating cells co-expressing the LGL marker (HNK-I) and the OKT8 antigen was detected in parallel with high IFN levels in NPC patients.
 ...
PMID:High interferon titer and defective NK-cell activity in the circulation of nasopharyngeal carcinoma patients. 253 26

The relative ability of TNF and lymphotoxin (LT) to inhibit the growth of five human tumor cell lines was examined both in the presence and absence of IFN-gamma. Two adenocarcinoma lines, HT-29 and SK-CO-1, were 20- and 320-fold more sensitive to the inhibitory effects of TNF and LT in 3- to 4-day proliferation assays. In contrast, the breast carcinoma line BT-20 showed only a one- to twofold difference. The MCF-7 and ME-180 cell lines exhibited intermediate behavior. These results parallel the reported disparate potencies of TNF and LT in their effects on endothelial cells, hematopoietic development and their abilities to sustain a mixed lymphocyte response. Radiolabeled TNF binding studies showed two classes of receptors (Kd 0.04 to 0.15 nM and 0.2 to 1.0 nM) on the highly sensitive SK-CO-1 line. HT-29 cells also appeared to possess some high affinity-binding sites, whereas the BT-20 line completely lacked the high affinity form. Thus the presence of high affinity-binding sites correlated with increased sensitivity to the antiproliferative effects of TNF. Cold TNF competed with the binding of radiolabeled human TNF three- to fivefold better than LT for binding to all three lines. These relatively small differences between the TNF and LT receptor-binding characteristics are insufficient to explain the dramatic disparity in their antiproliferative properties. Likewise, the absolute concentrations of the unlabeled cytokines necessary to block the binding of 125I-TNF were 10- to 150-fold higher than the levels necessary to elicit the biologic response. Thus, the receptor binding data conflict with the growth inhibitory effects. This discrepancy is discussed in terms of either separate receptors for TNF and LT or more complex phenomena such as receptor cooperativity possibly resulting from multivalent interactions with the trimeric form of TNF.
 ...
PMID:Studies on the differing effects of tumor necrosis factor and lymphotoxin on the growth of several human tumor lines. 255 May 45

The vast majority (71 of 77) of human tumor cells derived from various tissue origins were found to express specific membrane receptors for gamma-interferon (IFN-gamma). Six receptor-negative tumors were found among leukemic cells of lymphoid origin. Scatchard analysis with 125I-labeled human recombinant IFN-gamma revealed a similar binding affinity with a mean dissociation constant (Kd) of around 2 X 10(-11) M not only for various established cell lines, but also for leukemic and carcinoma cells derived from biopsy material. In contrast to similar KdS, large differences in the number of expressed IFN-gamma membrane receptors were found on distinct tumor cells of the same cell type ranging from a few hundred up to 2 X 10(4) for both carcinoma cells and leukemic cells. For comparison, the IFN-gamma receptor number on normal lymphocytes (mean, approximately 300/cell) and normal bone marrow cells (mean, approximately 1000/cell) was consistently found to be low. Cross-linking of membrane-bound 125I-IFN-gamma with disuccinimidyl suberate and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed, in both leukemia and carcinoma cells, three distinct complexes with molecular weights of approximately 70,000, 92,000, and 160,000, suggesting the existence of IFN-gamma receptor subunits. A dimeric structure of the functional IFN-gamma receptor with an estimated molecular weight of about 128,000 +/- 10,000 is proposed. Together with the Scatchard analysis, these data suggest the existence of a single class of high affinity IFN-gamma receptors in tumor cells of distinct tissue origin.
 ...
PMID:Quantitation and characterization of gamma-interferon receptors on human tumor cells. 294 78

The expression of human histocompatibility leukocyte antigen class II antigens on gastric epithelia and gastric carcinoma (GaCa) was studied with the use of murine monoclonal antibodies to DR, DQ, and DP antigens. DR and DP antigens but not DQ antigens were demonstrated in fundic glands of normal gastric epithelia, and DP+ cells were located in part of the DR+ epithelia. Of 15 GaCas examined, 11 expressed DR antigen, and the degree of the expression varied considerably among the specimens. DP antigen was found in 3 of the 11 DR+ carcinomas, and the DQ antigen was found in one of the 3 DR+ DP+ specimens. Thus the expression of class II antigens in normal gastric epithelia and GaCas appears to be in the order of DR, DP, and DQ. Studies on 3 GaCa cell lines (Kato III, MKN28, and MKN45) demonstrated that 1 line (Kato III) expressed DR antigen only, and the remaining lines were negative. Interferon (IFN)-gamma treatment enhanced the expression of DR antigen on Kato III cells and induced expression of DQ and DP antigens. The IFN-gamma treatment also induced expression of DR antigen but not DQ or DP antigens in 1 of the 2 negative cell lines. The induction of the class II antigens by IFN-gamma was shown to be dose dependent. However, maximal induction of DQ and DP antigens on the Kato III cells and DR antigens on MKN45 cells required 10 times more IFN-gamma than that needed for the maximal expression of DR antigen on Kato III. Northern blot analyses of cytoplasmic RNA from these cells were in agreement with and affirmed the above-described expression of the class II antigens on the cell lines. The DR antigen on the Kato III cells was capable of stimulating allogeneic lymphocytes in MLR, and its stimulatory activity was significantly enhanced by IFN-gamma. These results demonstrated a differential expression of class II antigens in the "DR, DP, and DQ order" in normal gastric epithelia, GaCa cells, and GaCa cell lines, suggesting different mechanisms acting discordantly on the expression of each of these antigens and that the DR antigen on the GaCa cell lines possesses MLR-stimulatory ability.
 ...
PMID:Expression and function of class II antigens on gastric carcinoma cells and gastric epithelia: differential expression of DR, DQ, and DP antigens. 296 Aug 47


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