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)

Lymphokine production by human melanoma tumor-infiltrating lymphocytes (TIL) was studied. Uncultured TIL produced interferon gamma (IFN gamma), but not interleukin-2 (IL-2) or IL-4, in response to anti-CD3 mAb or IL-2. In bulk cultures, IL-2-activated TIL displaying autologous tumor-specific cytotoxicity (CTL-TIL) produced IFN gamma in culture with medium alone, whereas IL-2-activated noncytotoxic TIL did not. Addition of anti-CD3 mAb or autologous tumor cells up-regulated IFN gamma production in IL-2-activated TIL from 10 of 12 or 6 of 12 cases respectively. Those from 4 of 12 cases (2 CTL-TIL and 2 noncytotoxic TIL) produced IL-2 in culture with medium alone. At the clonal level, 5 (4 CD4+ and 1 CD8+) of 7 autologous tumor-specific CTL clones derived from TIL and 3 (2 CD4+ and 1 CD8+) of 7 noncytotoxic TIL clones produced IFN gamma in culture with medium alone, which was up-regulated by adding anti-CD3 mAb. Two IFN gamma-producing CTL clones tested produced IL-2 in 4x-concentrated supernatants from a 3.5-h culture with medium alone. Furthermore, 2 IFN gamma-producing CTL clones tested expressed mRNA for both IFN gamma and IL-2. IL-2 production and its mRNA expression were up- or down-regulated, respectively, by adding anti-CD3 mAb or autologous tumor cells. IL-4 production was not observed in culture either with medium alone or with IL-2 in any of the cells described above. Anti-CD3 mAb was required for IL-4 production in 3 of 12 IL-2-activated TIL, 2 of 6 CTL clones, and none of 5 noncytotoxic TIL clones. In summary, IFN gamma production was characteristic of melanoma TIL. Some autologous tumor-specific CTL in TIL are suggested to be productive of IL-2 and IFN gamma under unstimulated conditions, both being required for self-activation in an autocrine loop.
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PMID:Lymphokine production by human melanoma tumor-infiltrating lymphocytes. 138 86

Autologous mixed lymphocyte-tumor cell cultures (MLTC) were initiated with cytokine (IFN gamma and TNF alpha)-treated ex-vivo tumor cells of lung, ovarian, breast and stomach carcinomas. The cytokine-treated tumors expressed class-I but not class-II molecules. Although the proportion of CD8+ lymphocytes increased in the bulk culture of MLTCs, in 5/7 experiments the majority of the established T-cell clones were CD4+. Among the CD8+ clones a high proportion (77%) was cytotoxic, while the proliferative response was more frequent among the CD4+ clones (70%). In 4/26 cytotoxic T-lymphocyte (CTL) clones (3/17 CD4+ and 1/9 CD8+), derived from a patient with class I+ class II- stomach carcinoma, lysis was restricted to the autologous tumor cells. These auto-tumor-specific clones did not lyse the autologous ConA blasts, the 5 allogeneic ex-vivo tumors, the NK-sensitive K562 or the relatively sensitive Daudi cells. The cytotoxicity of these clones was inhibited by pre-incubation of the tumor cells with W6/32 (alpha-class I) MAb, or by preincubation of the lymphocytes with OKT3 (alpha-CD3) MAb. The alpha-CD4 (OKT4) MAb had only a marginal effect on the CD4+ clones, while the lytic function of the CD8+ clone was inhibited by the alpha-CD8 (OKT8) MAb. The 3 CD4+ CTL clones also responded with proliferation to the autologous tumor cells. This proliferative response was inhibited by the presence of W6/32 MAb. Our results indicate that the auto-tumor lysis exerted by CD4+ CTL clones was restricted by the class-I antigens, and that the CD4 molecules of the clones were not essential for the lytic interaction.
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PMID:MHC class-I-restricted auto-tumor-specific CD4+CD8- T-cell clones established from autologous mixed lymphocyte-tumor-cell culture (MLTC). 138 48

The proto-oncogene C-jun acts as a transcriptional activator or repressor for numerous cellular genes, and the overexpression of these genes may cause malignant transformation. JunB inhibits c-jun's transforming activities. We investigated the expression of jun genes in renal cell cancer (RCC) and their regulation by cytokines and transforming growth factor beta 1 (TGF-b1). The constitutive expression of c-jun was detected in 39 of 43 fresh frozen RCC, 5 of 10 normal kidneys, and the expression of junB detected in 28 of 34 RCC, 5 of 6 normal kidneys. C-jun was also found expressed in all 10 RCC tumor lines examined and junB was expressed at low levels in 6 of 10 renal tumor lines. TGF-b1 and tumor necrosis factor alpha (TNF-a) have been shown to alter the expression of jun genes in other tissue types. Additionally, TGF-b1, TNF-a, and gamma interferon (g-IFN) were shown to inhibit the growth of RCC. We found that TGF-b1 highly augmented the expression of junB (mean of 34 folds, p less than .05), but did not significantly alter the expression of c-jun, the transforming gene. In contrast, TNF-a significantly enhanced the expression of both c-jun (mean fold enhancement of 2.1, p less than .05) and junB (2.2 folds, p less than .05). Interleukin-2 (IL-2), interleukin-4 (IL-4) and g-IFN did not significantly alter jun expression. The findings presented suggest that c-jun may have a role in inducing malignant transformation in RCC and a novel mechanism by which TGF-b1 may exert its anti-tumor effects, via the activation of junB. Additionally, although TGF-b1, TNF-a, and g-IFN all have anti-proliferative actions on RCC in vitro, they were found to have different effects in altering jun expressions.
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PMID:The expression of C-jun and junB mRNA in renal cell cancer and in vitro regulation by transforming growth factor beta 1 and tumor necrosis factor alpha 1. 140 66

Peritoneal macrophages obtained from Lewis Lung carcinoma (3LL) tumor bearing mice release high amounts of soluble factors such as C3,H2O2 and lysosomal enzymes but fail to exert cytotoxic activity on tumor cells. In the present work we show that they acquire this property and become fully activated after in vitro incubation with supernatants derived from cultures of splenocytes from tumor bearing syngeneic mice. The presence of IFN gamma in the above supernatants was detected by immunoblotting analysis and by bioassay. The role played by IFN gamma in macrophage activation was investigated.
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PMID:In vivo and in vitro macrophage activation induced by IFN gamma spontaneously released by spleen cells from tumor bearing mice. 141 66

The recognition and presentation of tumor-associated antigens by cutaneous antigen-presenting cells (APC) may play an important role in the establishment of effective defense mechanisms against newly emerging tumors in the skin. Recent data demonstrate the ability of I-A+ epidermal cells (Langerhans cells) to present tumor-associated antigens for the induction of protective tumor immunity and elicitation of delayed-type hypersensitivity against the murine spindle cell tumor, S1509a. Furthermore, the local cytokine microenvironment in the vicinity of a cutaneous neoplasm may regulate the ability of resident epidermal APC to initiate and/or to elicit protective immunity against incipient cutaneous neoplasms. This article summarizes the effects of granulocyte-macrophage/colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF alpha), transforming growth factor-beta (TGF beta), and interferon-gamma (IFN gamma) on the modulation of antigen presentation by epidermal APC. Our data indicate that these cytokines significantly and differentially modify the ability of epidermal cells to present tumor-associated antigens and that their effects differ with regard to induction of primary immunity (sensitization) or elicitation of secondary immune responses.
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PMID:Effects of immunomodulatory cytokines on the presentation of tumor-associated antigens by epidermal Langerhans cells. 143 Dec 32

The clinical tolerance of and the effects recombinant human interferon-beta (rHuIFN-beta) obtained from mammalian cells (Chinese hamster ovary cells) exerts on 2',5'-oligoadenyl (2-5A) synthetase activity, human-Mx protein, neopterin, beta 2-microglobulin, interleukin-1 (IL-1) alpha and beta synthesis were compared to those of natural IFN-beta in 12 healthy volunteers. Each subject received a single i.m. injection of 6 x 10(6) IU rHuIFN-beta and natural IFN-beta according to a randomized double-blind cross-over study design. Both were well tolerated and provoked similar changes in clinical indices. Moreover, rHuIFN-beta and natural IFN-beta induced significant and similar increases in 2'-5' adenylates, human Mx protein, and neopterin levels, but neither modulated beta 2-microglobulin, IL-1 alpha or beta synthesis. The sum of these findings indicates that rHuIFN-beta and natural IFN-beta are biologically equivalent. In view of these results, we are of the opinion that these two types of IFN are probably also therapeutically equivalent and, in consequence, that trials to evaluate the response of viral and neoplastic disease patients to rHuIFN-beta are fully justified.
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PMID:Double-blind randomized phase I study on the clinical tolerance and biological effects of natural and recombinant interferon-beta. 143 12

Tumor-infiltrating lymphocytes (TIL) were tested for cytotoxicity against autologous tumor cells in a study utilizing a chemically induced cancer of the bladder (transitional cell carcinoma), BC-47, in inbred ACI/N rats. From tumors grown after subcutaneous implantation of BC-47 in the rats TIL were separated by density gradient centrifugation and incubated in plastic dishes for separation of non-adherent from adherent cells. The non-adherent cells were further fractionated into T and B cells by the panning method using anti-rat F(ab')2 antibody. The cell fractions were each added to BC-47 in culture to be assessed for antitumor effect by the crystal violet dye exclusion method and 3H-thymidine incorporation inhibition assay. Peripheral blood mononuclear cells (PBMC) were also tested as described above. TIL expressed significantly higher cytotoxicity against BC-47 with the mean % cytotoxicity of 56.6 +/- 5.6% and 87.5 +/- 7.1% at E/T ratios of 10:1 and 20:1, respectively, as compared to PBMC (9.9 +/- 5.0% at E/T 10:1) (P < 0.001). The adherent cells, B and T cell fractions showed respective % cytotoxicity of 92.4 +/- 2.8%, 57.9 +/- 10.6% and 9.9 +/- 7.8% at an E/T ratio of 10:1. TIL pretreated with IFN or rIL-2 for 24 or 48 hours did not exhibit any noticeably enhanced antitumor activity at an E/T ratio of 5:1. Prevention of direct contact of BC-47 cells and TIL by an interposed Millipore membrane (0.45 microns) resulted in an unequivocal reduction of antitumor effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cell-mediated cytotoxicity of tumor infiltrating lymphocytes on rat bladder cancer. 143 9

Cytokine-induced modulation of HLA expression on the cell surface of four human breast cancer cell lines was determined by continuous flow immunocytofluorometry with the aid of monoclonal antibodies directed to a non-polymorphic determinant of HLA class I and class II (DR) antigen. IFN-gamma and IFN-alpha were potent inducers of HLA class I in all examined cell lines, with decreasing inducibility as follows: BT-20, ZR-75-1, MCF-7 and MDA-MB-468 cells. HLA class II (DR) antigen was highly inducible by IFN-gamma in ZR-75-1 cells, followed by BT-20, MDA-MB-468 and MCF-7 cells. IFN-alpha increased the cell surface expression of DR antigen only in ZR-75-1 cells. IL-1-alpha induced a moderate level of HLA class I antigen in ZR-75-1, BT-20 and MDA-MB-468 cells, and HLA class II (DR) expression only in ZR-75-1 cells. This pattern of cell line inducibility by IL-1-alpha was similar to that induced by TNF-alpha. Differences in inducibility of HLA antigens on human breast cancer cell lines induced by different cytokines may reflect the differences in cytokine inducibility of the original tumor cells.
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PMID:Cytokine (IFN-alpha, IFN-gamma, IL-1-alpha, TNF-alpha)-induced modulation of HLA cell surface expression in human breast cancer cell lines. 143 41

Since the cell cycle of tumor cells is evaluable with the aid of flow cytometry, the mechanism of action of antineoplastic agents has readily been analyzed based on the changes of the cell cycle by antineoplastic agents. Propidium iodide had been a conventional staining method for such analysis, but after the introduction of DNA/BrdU double staining method using BrdU, it has become much easier. For evaluating antineoplastic agents, simultaneous measurement by FDA of the viability of the tumor cells is important. In vitro studies of the action mechanism and the antineoplastic effects of 5-FU, ACNU, IFN, PG, CDDP, PEP, and HCFU have been reported previously elsewhere. Similar action mechanism has been confirmed in clinical studies, in which optimal agent was selected by the sensitivity test using flow cytometry, and thus selected agent was actually given to tumor patients. In analyzing antineoplastic agents in vitro, concomitant and total evaluation of DNA-histogram and viability by flow cytometry is needed in the future.
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PMID:[Flow cytometric analysis, mechanism of action and evaluation of viability by antineoplastic agents]. 144 5

An open randomized trial was performed to compare the effect of recombinant interferon-alpha 2a (rIFN-alpha 2a) (group A, n = 12) versus rIFN-alpha 2a in combination with chemotherapy (group B, n = 11) in patients with malignant carcinoid tumors. Both groups received rIFN-alpha 2a at a dose of 3 MU/m2 s.c. three times weekly during the first 6 months. IFN was discontinued every third week in group B, followed by an i.v. injection of 2 g streptozocin and 40 mg/m2 doxorubicin. After 6 months group A showed one complete biochemical response (CR), 9 patients with stable disease (SD) and 2 who progressed (PD). Two patients had a partial reduction (PR) of tumor size, 9 showed SD and one PD. All patients in group B demonstrated SD. Chemotherapy was withdrawn after 6 months and all patients continued with rIFN-alpha 2a at an increased dose of 3 MU/m2 five days/week for a further 6 months. After 12 months 6 patients showed PR, 12 SD and one PD biochemically. Tumor size showed SD in 18 patients and PD in one. One patient died from cardiomyopathy, probably induced by doxorubicin. Antibodies against rIFN-alpha 2a developed in 41% of the patients. In conclusion, we detected no difference in response rates between the two treatment groups. Adverse reactions from the combination were considerable. The frequent development of IFN antibodies might have interfered with the therapeutic results.
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PMID:Treatment with alpha-interferon versus alpha-interferon in combination with streptozocin and doxorubicin in patients with malignant carcinoid tumors: a randomized trial. 145 46


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