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)

The effects of the i.v. administration of endotoxin (6.25-50 micrograms/mouse on day 13 after tumor implantation) in mice treated orally with lysozyme hydrochloride (100 mg/kg on days 5-12 from tumor implantation) were examined using Lewis lung carcinoma in the C57Bl mouse and MCa mammary carcinoma of CBA mice. On primary tumor growth, endotoxin alone causes a dose-dependent and statistically significant reduction with a nadir on day +2 from endotoxin treatment. Combined with lysozyme, endotoxin causes an effect independent of the dose used, corresponding to the effect caused by endotoxin alone at the dose of 25 micrograms/mouse. No tumor regression was recorded in any of the treated groups. Endotoxin is virtually devoid of effects at the metastatic level. In the same conditions, lysozyme causes a reduction of primary tumor growth and a more pronounced inhibition of lung metastasis formation as expected from its already reported effects. The antitumor activity of endotoxin, unlike lysozyme, can be ascribed to tumor hemorrhagic necrosis due to tumor necrosis factor (TNF) production, as determined in tumor homogenates. Endotoxin does not increase the antitumor effects in mice treated with lysozyme, as expected from the data obtained with the more immunogenic SA1 sarcoma, although lysozyme increased the mitogenic response to ConA of ex vivo isolated splenocytes, in vitro cultured in the presence of IL-2.
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PMID:Effects of endotoxin in mice bearing solid metastasizing tumors and treated with lysozyme hydrochloride. 140 79

Recombinant interleukin-2 (rIL-2) is able to maintain the growth and multiplication of T-lymphocytes and IL-2 dependent CTLL-2 cells up to 28 days with the multiplication of T-lymphocytes as high as about 1000 fold. When rIL-2 and its monoclonal antibody were added together, the above functions of rIL-2 were specially blocked, showing that these biological functions were exerted specifically by rIL-2. The rIL-2 is also able to increase the natural killer (NK) activity up to 46-96%, while higher concentrations of rIL-2 might exhibit inhibitory effect. The cytotoxicity of lymphokine activated killer (LAK) cells induced by rIL-2 for killing HL-60 cell line and solid tumour (human lung carcinoma) reached 54.84% and 37.96%, respectively. All these results indicate that the biological functions of rIL-2 were quite similar to that of the natural one.
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PMID:Biological functions of recombinant human interleukin-2. 177 13

In an attempt to further understand the biological significance of soluble IL-2 receptors (sIL-2R) in solid tumors, we have evaluated 160 cancer patients (breast: 40; lung: 66; colon: 18; stomach: 22; uterine cervix: 14) and 58 healthy subjects, as controls. Serum mean levels of sIL-2R, measured with an enzyme immunoassay, were significantly higher in cancer patients than in controls. Metastatic cancer patients showed significantly higher values than the non-metastatic ones; this difference was significant in all tumor histotypes, except small cell lung carcinoma. Moreover, in 15 patients in whom sIL-2R were evaluated either before or after radical surgery, a significant surgery-induced increase in sIL-R mean values was seen. Finally, the chemotherapy-induced rise in sIL-2R appeared to be associated with a lack of clinical response. These results seem to suggest that sIL-2R may be a marker of host biological response in patients with solid tumors, the significance of which needs further investigation.
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PMID:The biological significance of soluble interleukin-2 receptors in solid tumors. 213 75

Understanding local pulmonary immunoregulatory mechanism(s) in patients with carcinoma of the lung is an important step towards the development of innovative methods of treatment. Prostaglandin E2 plays an integral role in immunoregulation. Therefore, we evaluated PGE2 concentrations in BALF from 18 patients with bronchogenic carcinoma, compared to that from six patients with pulmonary diseases other than carcinoma and ten normal smokers of similar age. The level of PGE2 in patients with lung carcinoma (158.1 +/- 88.7 pg/ml) was significantly (p less than 0.001) higher than the other two groups (16.2 +/- 6.9 and 4.4 +/- 3.4 pg/ml). Levels of PGE2 also varied among patients with carcinoma of different cell types. Patients with SQCA had significantly (p less than 0.001) higher levels of PGE2 (242.7 +/- 29.4 pg/ml) than patients with ADCA or SCCA (82.3 +/- 27.9 and 66.3 +/- 15.2 pg/ml, respectively). Furthermore, there was a marked difference in PGE2 concentration between carcinomatous lung and clinically noninvolved lung in patients with SQCA and ADCA. Further study is warranted to determine the interactions between PGE2 and other cytokines (interleukin-1, IL-2, and tumor necrosis factor), as well as the activity of cytolytic lymphocytes (LAK cells) in the lungs of patients with bronchogenic carcinoma.
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PMID:Elevated prostaglandin E2 levels in bronchoalveolar lavage fluid of patients with bronchogenic carcinoma. 217 96

Tumor infiltrating (TIL) and peripheral blood lymphocytes (PBL) were isolated from 18 patients with non-small cell lung cancer undergoing radical surgery. Surface marker analysis revealed that TILs and PBLs mainly consisted of CD3+ T cells and that TILs generally displayed a lower CD4/CD8 ratio. Differences were found in the expression of CD25 (IL-2 receptor) and DR (MHC class II) antigens, which were increased in TILs, and in the percentage of CD16+ natural killer (NK) cells, which was reduced in TILs as compared to PBLs. Accordingly, the NK activity of TILs was lower than that of PBLs, whereas neither TILs nor PBLs expressed spontaneous cytolytic activity against fresh autologous tumor cells, melanoma cells and the "NK-resistant" A549 lung carcinoma cell line. After 4 days of culture in medium with recombinant-interleukin-2 (rIL-2), TILs and PBLs acquired cytolytic activity against all cell targets, but TILs expressed higher levels of cytotoxicity than autologous PBLs only in 3 patients out of 16 tested. More importantly, both TILs and PBLs displayed similar levels of cytotoxic activity against autologous tumor cells. TILs and PBLs from 8 patients were also analyzed by a limiting dilution microculture system. Cloning efficiency was remarkably lower in TILs, and surface marker analysis of T cell clones confirmed that an accumulation of CD8+ lymphocytes, which displayed cytolytic activity in a lectin-dependent assay, occurred at the tumor site. The non-MHC-restricted cytolytic activity of TIL- and PBL-derived T cell clones against K562, A549, and allogeneic melanoma cells and the cytolytic activity against autologous tumor cells showed no significant differences. Only 53% of TIL clones released IL-2 in response to PHA + TPA stimulation, whereas 68% of PBL-derived clones were IL-2 producers. Moreover, most PBL- and TIL-derived clones released tumor necrosis factor alpha in response to mitogen stimulation.
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PMID:Peripheral blood and tumor infiltrating lymphocytes in non-small cell lung cancer: analysis at the population and clonal level. 217 60

Adoptive immunotherapy with LAK-cells in conjunction with high-dose IL-2 has recently been introduced in the treatment of patients with advanced cancer. This therapeutic modality has thus far proved to be of limited efficacy, severe toxicity and entails complicated logistics. Our present study is aimed at establishing a model system to test for increasing efficacy and reducing toxicity by using AIT cojointly with chemotherapy. Mice implanted i.v. or i.p. with weakly immunogenic tumors (M109 lung carcinoma, MCA-105 sarcoma) were treated 7 to 20 days after tumor inoculation with or without CTX, with and without recombinant human IL-2, and with and without syngeneic/allogeneic LAK-cells. Whereas IL-2 or IL-2 + LAK-cells without CTX was largely ineffective, and CTX alone cured 0 to 20% of the animals with an i.p. tumor and only slightly reduced pulmonary tumor mass, the combination of CTX + IL-2 cured 50 to 80% of the mice bearing i.p. tumors and reduced pulmonary tumor growth by greater than or equal to 80%. The combination of CTX + IL-2 + LAK-cells proved no more beneficial than CTX + IL-2 without LAK-cells. Also relevant were the observations that murine LAK-cells are transiently sensitive to moderate doses of CTX (greater than or equal to 100 mg/kg body weight) and X-irradiation (greater than equal to 400 rad), and that administration of IL-2 by the i.v. or i.p. route variously affects LAK-cell activation in different tissues and eradication of growths localized at different sites. With the regimens used, no signs of toxicity were detected. It is proposed that instillation of IL-2 (and perhaps of additional immunostimulating cytokines as well) as an adjunct to chemotherapy (or chemoradiotherapy), each given at a subtoxic dose, is both safe and effective in the treatment of metastatic advanced tumors, and that the additional administration of LAK-cells may not be required.
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PMID:Therapy of advanced solid tumors in mice using chemotherapy in combination with interleukin-2 with and without lymphokine-activated killer cells. 326 51

Gene therapy with cytokine cDNA will provide a new tool for cancer treatment. We have already reported that immunization with interleukin-2 (IL2) cDNA transfected Lewis lung carcinoma (LLC) cells induced anti-tumor immunity, which, however, was not strong enough to eradicate an established tumor. In an attempt to develop more effective gene therapy methods, we have used tumor cells co-transfected with IL-2 and tumor necrosis factor (TNF) cDNAs. These cDNAs were introduced into pBMG-Neo and pcDV-X819 vectors, respectively, and then co-transfected into LLC cells. The co-transfectants were selected by incubating them in a medium containing G418 followed by the limiting dilution method twice to obtain IL2 and TNF cDNA co-transfected LLC (LLC-TNF-IL2) cells. When 5 x 10(5)/ml LLC-TNF-IL2 cells were incubated for 48 h, they secreted 7.56 U/ml TNF and 527.0 U/ml IL2 into the culture supernatant. When C57BL/6 mice were transplanted with 1 x 10(6) LLC-TNF-IL2 cells, all the tumors were rejected. The growth of transplanted LLC, but not B16F10 melanoma cells, was retarded in mice inoculated with LLC-TNF-IL2 on their contralateral sides, which suggests specific immunity was induced. The immunization effect by the co-transfectant was superior to that of the IL2- and TNF-transfectants alone.
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PMID:Gene therapy for Lewis lung carcinoma with tumor necrosis factor and interleukin 2 cDNAs co-transfected subline. 758 91

Lewis lung carcinoma (LLC-LN7) tumors stimulate myelopoiesis and induce immunosuppressive granulocyte-macrophage (GM)-progenitor cells. Treating mice having palpable tumors with IL-12 enhanced the frequency of GM-progenitors and did not diminish GM-suppressor activity. Proliferation of splenic T-cells of tumor-bearers to Con-A or to anti-CD3 plus IL-2 was suppressed; this was not enhanced by IL-12 treatment. Also not stimulated was T-cell secretion of IL-2 in response to autologous tumor, or the intratumoral T-cell content. IL-12 slightly increased splenic IFN-gamma secretion, and increased cytotoxicity of lymph node (but not spleen) cells toward autologous tumor. In these tumor-bearing mice that were immune depressed as a result of GM-suppressor cells, immune modulatory effects of IL-12 were marginal and did not affect tumor size or metastasis.
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PMID:Ineffective immune enhancement by IL-12 in tumor-bearing mice whose immune depression is mediated by suppressive granulocyte-macrophage progenitor cells. 760 May 36

Effectiveness of bispecific-monoclonal-antibody (BsMAb)-mediated cellular anti-tumour activity was evaluated in vitro and in vivo in relation to the additional need for T-cell activation in a new immunocompetent rat tumour model. L37 tumour cells, derived from a squamous-cell carcinoma of the lung of Wag/Rij rats, were transfected with the cDNA coding for the human 38-kDa transmembrane pan-carcinoma-associated antigen EGP-2. Intravenous inoculation of EGP-2-positive L37 cells resulted in a rapid outgrowth of EGP-2-positive tumour nodules in the lungs. A BsMAb BIS-19, recognizing EGP-2 on the transfected tumour cells and the T-cell receptor of the rat, was made and allowed specific lysis of EGP-2-transfected L37 tumour cells by activated rat T lymphocytes in vitro. In vivo T-cell activation, assessed by up-regulation of IL-2-receptor expression, could be induced by daily injection of rat rIL-2. Intravenous treatment of tumour-bearing EGP-2-positive L37 tumour with BIS-19 together with rat rIL-2 resulted in almost complete disappearance of established tumour. In contrast, animals treated with BIS-19 alone, IL-2 alone or a combination of anti-EGP-2, anti-TcR and IL-2 showed much less or no tumour reduction. These results show effectiveness of systemic treatment with BsMAbs to induce anti-tumour activity in established tumours. Immune activation prior to or during treatment with BsMAbs, as achieved with IL-2, appears to be a prerequisite for successful treatment.
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PMID:Reduction of EGP-2-positive pulmonary metastases by bispecific-antibody-redirected T cells in an immunocompetent rat model. 779 Jan 16

Three new peroxylactones, plakortolides B [6], C [7], and D [8], and a new peroxy ester, epiplakinic acid E methyl ester [9], were isolated and characterized from a previously unstudied marine sponge, Plakinastrella onkodes. A mixture of steroidal peroxides was also found in this organism. Plakortolides B [6] and D [8], and epiplakinic acid E methyl ester [9], were evaluated for biological activity and found to show cytotoxicity against the A549 human lung carcinoma and P388 murine leukemia cell lines, and to effect adhesion in an assay employing the EL-4.IL-2 cell line, which correlates with signal transduction activity.
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PMID:New cytotoxic peroxylactones from the marine sponge, Plakinastrella onkodes. 780 22


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