Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Controversy exists as to whether interferons usefully influence the growth of epithelial carcinomas. A small cell lung carcinoma (SCLC) cell line, WX322, has been derived which is greater than 1000-fold more sensitive to alpha-interferon (IFN) when grown in agar than other reported SCLC cell lines. The WX322 line has been characterised to prove its epithelial origin and its chemosensitivity compared with that of the NCI-H69 small cell line. The WX322 cell line expresses neuroendocrine and epithelial markers and possesses a morphology consistent with SCLC origin. A concentration of 5 IU ml-1 of IFN produced 50% inhibition of colony formation in agar in the WX322 line, whereas a concentration of greater than 10(5) IU ml-1 was required to produce a comparable effect with the NCI-H69 cell line. In contrast, WX322, possessed similar sensitivity to NCI-H69 cells when exposed to a range of cytotoxic agents. Analysis of the cell cycle indicated that IFN increased the percentage of cells in the G0/G1 phase for the WX322 cell line but increased the percentage in S phase for the NCI-H69 line. Growth of the xenograft, from which the cell line was derived, was also inhibited by IFN at doses greater than 10(5) IU/mouse/day. The WX322 cell line whether grown in agar or as a xenograft shows an unusually high sensitivity to IFN and provides an interesting model for studying mechanisms of IFN cytotoxicity to epithelial cells.
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PMID:Characterisation and properties of a small cell lung cancer cell line and xenograft WX322 with marked sensitivity to alpha-interferon. 171 22

The possibility for new interferon therapy was investigated using the effect of endogenous human interferon-beta (HuIFN-beta) on various culture cell lines. Cell lines were exposed to superinduction agents (poly I: poly C, cycloheximide, and actinomycin D) and the production of endogenous interferon analyzed. Quantitative determination of HuIFN-beta and messenger ribonucleic acid (mRNA) showed HuIFN-beta was induced in all of five glioma cell lines, one of two melanoma cell lines, and all of three lung carcinoma cell lines as well as fibroblasts. Northern blot analysis showed HuIFN-beta mRNA induced in glioma cells was identical to that from fibroblasts. Endogenous HuIFN-beta induced from glioma cells had a cytostatic or cytocidal effect against various human glioma cell lines, even those resistant to fibroblast-derived HuIFN-beta. These results show it may be possible to use the induction of excess endogenous cytotoxic HuIFN-beta in human glioma tissue itself.
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PMID:Superinduction of cytotoxic interferon-beta in glioma cells. 172 75

Macrophages are thought to play an important immune effector cell role in antitumor host defense. It remains unclear whether PAM antitumor activity in patients with lung cancer is normal or impaired. We examined PAM cytostasis in patients with lung cancer and in control subjects and determined whether the in vitro PAM response could be enhanced by gamma-interferon. Nineteen patients with primary lung carcinoma and 15 control patients underwent BAL. Five patients with cancer underwent lavage of both lungs to assess whether any abnormality found related to tumor proximity or was part of a more generalized defect. Cytostatic activity was assessed by measuring inhibition of incorporation of tritiated thymidine into the target cell U937. There was a significant difference in baseline cytostatic activity between patients with cancer (mean +/- SE, 59 +/- 7 percent) and control patients (92 +/- 2 percent) (p less than 0.0002). The increase in cytostatic function after stimulation with gamma-interferon (1,250 units/ml) was higher in the group with cancer (28 +/- 5 percent increase from baseline) than in controls (5 +/- 1 percent) (p less than 0.0005). Cytostasis after stimulation was not significantly different between the groups. In the bilaterally lavaged group, baseline cytostatic activity was not different between cancerous and noncancerous lungs and was again significantly lower than in control subjects. These results indicate (a) that PAM baseline cytostatic activity in patients with cancer is lower than in controls, (b) that gamma-interferon can significantly augment cytostatic function in patients with cancer, to levels comparable with those achievable in control patients, and (c) that the PAM abnormality is part of a generalized immune defect in lung cancer and does not simply reflect a local response to the carcinoma. It may be inferred from these results that PAMs from patients with primary lung cancer are not fully stimulated in vivo and that a defect of T cell lymphokine production may underlie the macrophage dysfunction.
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PMID:Defective cytostatic activity of pulmonary alveolar macrophages in primary lung cancer. 193 23

Expression of HLA-DR antigens and Fc IgG receptors as well as C3 complement component, was studied on patients with the primary lung carcinoma and in the control group of nonsmokers and smokers. Macrophages were isolated by broncho-alveolar lavage using bronchofiberoscope. The study was carried out before the treatment, within its course and during remission. The percentage of macrophages with HLA-DR antigens and Fc IgG receptors and C3 complement was observed to diminish before the treatment, after chemo- and radiotherapy as compared to the control. In the course of alpha interferon-treatment and at remission, the expression of HLA-DR antigens on macrophages increased in relation to the remaining groups of patients (p less than or equal to 0.05). The expression of Fc IgG receptors and C3 complement revealed no statistically significant differences. As the findings show the expression of HLA-DR antigens is modulated by interferon and has a tendency to increase in the course of convalescence. On the other hand, the expression of RFc IgG and RC3 complement shows great stabilization in the primary lung carcinoma and undergoes no changes either in the course of treatment or remission.
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PMID:Study on the expression of HLA-DR antigens, Fc IgG receptors and C3 complement component on lung macrophages in the primary lung carcinoma. 215 44

Cadeguomycin retarded growth of sc solid IMC carcinoma in CDF1 mice, and pulmonary metastasis of Lewis lung carcinoma in C57BL/6 mice. The antibiotic enhanced phagocytic activity of murine peritoneal macrophages and IL-1 production by P388D1 cells. Delayed type hypersensitivity was stimulated and interferon was induced by the drug. The results suggest that cadeguomycin inhibits tumor growth and metastasis in association with modification of the immune system. The cytotoxicity of arabinosylcytosine to K562 and YAC-1 cells was markedly enhanced by cadeguomycin in culture. The combined administration of arabinosylcytosine and cadeguomycin displayed potentiation in the inhibition of growth of ip-implanted P388 leukemia and metastasis of sc-implanted P388 leukemia to the regional lymph nodes. Cadeguomycin showed low toxicity for mice.
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PMID:Biological activity of cadeguomycin. Inhibition of tumor growth and metastasis, immunostimulation, and potentiation of 1-beta-D-arabinofuranosylcytosine. 241 Mar 97

Four human tumor cell lines were studied for their response to antiproliferative effects of various interferons (IFNs) alone and in combination with the novel mismatched dsRNA, r(I)n r(C12,U)n (Ampligen). RT4 cells (bladder carcinoma) were resistant to Ampligen alone, while A2182 (lung carcinoma), HT 1080 C14 (fibrosarcoma) and RT112 (bladder carcinoma) cells were inhibited in a dose-dependent manner. In contrast, RT4 cells were sensitive to the antitumor effects of IFNs as were HT1080 C14 and RT112 cells, while A2182 cells were resistant. In 3 of 4 cell lines, the recombinant IFNs were less effective than the corresponding natural IFNs when compared by analysis of variance on an IRU/ml basis over a range of concentrations. In all cell lines, a synergistic antiproliferative effect was seen with all IFN preparations studied in combination with Ampligen, as calculated by the isobole method according to Berenbaum (1981). The antiproliferative effect of IFN was potentiated greater than 3.3- to greater than 250-fold, depending on the cell lines, IFN, and concentrations used. Varying the concentration of beta ser-IFN while holding the Ampligen concentration constant gave synergy at all of the physiologically achievable concentrations tested in RT4 cells. These results indicate that: Ampligen worked synergistically with all IFNs in all cell lines studied; growth inhibition of cells resistant to IFNs can be potentiated by low doses of Ampligen; the antiproliferative effect of IFNs can be potentiated by Ampligen in Ampligen-resistant cells; and Ampligen may work by a mechanism other than, or in addition to, the induction of IFNs.
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PMID:Synergistic antiproliferative effect of human interferons in combination with mismatched double-stranded RNA on human tumor cells. 241 65

The effects of treatment of human lung carcinoma cell line A 549 with recombinant DNA-derived human leukocyte interferons A (rIFN-alpha A) or D (rIFN-alpha D), and human lymphoblastoid interferon (Wellferon) on in vitro cell invasion were investigated in a quantitative invasion assay using human amnion. The A 549 cells treated with IFN for one day were incubated on the denuded basement membrane of the amnion in the absence of IFN, and cells which penetrated the full thickness of the connective tissue barrier were measured after 4 days. A dose-dependent inhibition of cell invasion was produced by the recombinant IFNs. The one day treatment of cells with 2.4 X 10(3) to 1.8 X 10(4) units/ml of rIFN-alpha A resulted in a 60-80 per cent inhibition of invasiveness compared to untreated cells. After a one day exposure of cells to 2.2 X 10(4) units/ml of rIFN-alpha D, cell invasion was reduced by approximately 70 per cent; a concentration of 4.4 X 10(3) units/ml had no apparent effect. Similar treatment with lymphoblastoid IFN (6 X 10(4) units/ml) had no significant effect on cell invasion. Accompanying the one day exposure to rIFN-alpha A (1.8 X 10(4) units/ml) or rIFN-alpha D (2.2 X 10(4) units/ml), (2',5') oligo (A) synthetase activity was induced approximately 20-fold; a 4-fold induction of enzyme activity was found in cells exposed to lymphoblastoid IFN (6 X 10(4) units/ml). After exposure of A 549 cells to the three IFNs at these concentrations, no significant alteration of the ability of the cells to attach to the basement membrane was found. Moreover, none of the one day IFN treatment regimens were cytocidal, and cell proliferation ability was not affected. This model system may be useful for investigating anti-invasive activity of other IFN types and subtypes.
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PMID:Treatment with human recombinant leukocyte interferons inhibits in vitro invasive ability of human lung carcinoma cells. 242 70

Thymostimulin (TS), a partially purified thymic factor, has a significant impact on tumor development in C57B1/6 mice inoculated with Lewis lung carcinoma (3LL) cells, as judged by its effect on time of tumor appearance after tumor cell transplantation. In a previous study, we determined the conditions under which survival rate of the tumor-bearing mice can be significantly increased by TS treatment. In the study communicated here we analyzed host defense mechanisms that are modified by TS treatment in the tumor-bearing mice. In general, immune parameters that were increased or stimulated by the presence of the tumor were further increased in the TS-treated animals (number of lymphoid spleen cells, their response in mixed lymphocyte tumor cultures, their natural killer cell activity, and their ability to produce colony-stimulating factor), or reached earlier maximum levels (spontaneous [3H]thymidine incorporation, a reflection of in vivo spleen cell activation). Responses which reflect tumor-induced immunosuppression (proliferative response induced by phytohemagglutinin or concanavalin A stimulation) were restored to normal level by TS. Specific tumor-related reactions (specific cell-mediated cytotoxicity) were preserved in the TS-treated animals. The wide spectrum of TS effects had, nevertheless, certain elements of selectivity; e.g. colony-stimulating factor, but no interferon production is enhanced by TS in the tumor-bearing mice in diametric contrast to TS effect in Mengo virus-infected mice. The spectrum of TS effects was also dependent on the type of tumor cell used. The results indicate that the significant effect of TS on 3LL tumor development in mice is associated with a strong, multifaceted effect of TS on the immune system.
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PMID:Modulation of immune response and tumor development in tumor-bearing mice treated by the thymic factor thymostimulin. 243 37

Immunochemical methods were used to examine the effect of viral infection on the dynamics of intracellular ubiquitin pools. Infection of either the human lung carcinoma line A-549 or the mouse fibroblast line L929 with encephalomyocarditis virus had little effect on either the distribution or fractional level of intracellular ubiquitin conjugates. In contrast, viral infection resulted in a significant decline in the steady state content of the mono-ubiquitin conjugate to histone 2A (uH2A). Prior treatment with interferons protected against this decrease of uH2A. Furthermore, interferons induced the de novo synthesis of a 15-kDa protein immunologically related to ubiquitin. The ubiquitin cross-reactive protein (UCRP) was not constitutively present in control cells but was significantly induced in various cells sensitive to the biological effects of interferons. Induction of UCRP with respect to both time and interferon concentration dependence closely paralleled the appearance of resistance to viral infection and could be blocked by low levels of actinomycin D. Subsequent studies demonstrated that UCRP was identical to an interferon-induced 15-kDa protein whose sequence has recently been reported (Blomstrom, D. C., Fahey, D., Kutny, R., Korant, B. D., and Knight, E. (1986) J. Biol. Chem. 261, 8811-8816). An authentic sample of the 15-kDa protein was found to co-migrate with UCRP and to cross-react with two different anti-ubiquitin antibodies. Using the authentic 15-kDa protein as a standard, UCRP accumulated to 6.2 +/- 0.5 pmol/10(6) cells and 34 +/- 2 pmol/10(6) cells in interferon-treated A-549 and L929 cultures, respectively. Comparison of the primary sequence of the 15-kDa protein to that of ubiquitin indicated that the former is composed of two domains, each of which bears striking homology to ubiquitin. These observations suggest that the 15-kDa protein may represent one example of a functionally distinct family of ubiquitin-like proteins.
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PMID:Interferon induces a 15-kilodalton protein exhibiting marked homology to ubiquitin. 244 Aug 90

We have used several transplantable experimental murine tumors to evaluate the potentiation of antitumor activity by a combination of human recombinant interleukin 2 (rHIL2) and recombinant interferons (rIFNs). The combination of rHIL2 and either human hybrid recombinant alpha-interferon A/D (rIFN-alpha A/D) or mouse recombinant beta-interferon (rIFN-beta) induced the s.c. adenocarcinoma 755, which had been established for 8 days, to regress, although rHIL2 or the rIFNs alone hardly inhibited the tumor's growth. Eight injections of the rHIL2-rIFN-alpha A/D combination cured 38% of the tumor-bearing mice. The rHIL2-rIFN-beta combination achieved a complete cure only when given in more than 13 injections. The administration of rHIL2 and mouse recombinant gamma-interferon (rIFN-gamma) markedly inhibited tumor growth of the s.c. established adenocarcinoma 755, but did not cure any of the mice. Other tumors, B16-F10 melanoma, and colon tumors 38 and 26 responded almost as well to a rHIL2-rIFN-alpha A/D or -beta combination, but not to a rHIL2-rIFN-gamma combination. The growth of Lewis lung carcinoma was inhibited to a lesser extent by all combinations, for which there were no long-term survivors. The combination therapy of rHIL2 and rIFN-beta produced a marked regression of the tumor in beige mice which have low natural killer activity, suggesting the activated natural killer cells not to be responsible for the therapeutic effect. And T-cell immunity may be important in the regression of s.c. established tumors, because of the lesser potentiation of antitumor activity in athymic mice. These results demonstrate that combination therapies of rHIL2 and rIFN-alpha A/D or -beta can function synergistically in the various s.c. established murine tumor systems and give further evidence in support of their clinical potential.
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PMID:In vivo antitumor activity of multiple injections of recombinant interleukin 2, alone and in combination with three different types of recombinant interferon, on various syngeneic murine tumors. 244 44


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