Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of combination chemotherapy in the treatment of advanced non-small-cell lung cancer is controversial. At best, a small survival benefit can be achieved. Therefore, other treatment modalities are needed. On the basis of the promising treatment results with interleukin-2 (IL-2) -containing immunotherapy in renal cell cancer and melanoma, we performed a phase I-II study with IL-2 and interferon alpha (IFN-alpha). Eligible patients were treated with IL-2 18 x 10(6) IU/m2/day by continuous intravenous infusion (c.i.v.) for 3 days. On the same days, 5 x 10(6) U/m2/day IFN-alpha was given intramuscularly. After a rest period of 4 days, patients at the first dose level received IL-2 2.4 x 10(6) IU/m2/day c.i.v. for a period of 28 days, followed by 14 days' rest, 14 days' treatment, 7 days' rest, and a final treatment for 14 days. Patients at the second dose level were treated according to the same schedule, in which the dose of IL-2 was increased to 3.6 x 10(6) IU/m2/day. During low-dose IL-2 treatment, patients received IFN-alpha 5 x 10(6) U/m2/day on days 1 and 4 of each week. Eleven patients were admitted to the study, six at the first and five at the second dose level. Median age was 54 years; all patients had a performance status of 0 or 1. The most important adverse effects included anorexia, fatigue, nausea, and headache, which were not dose limiting. In the 11 patients treated, no responses were seen. Nine patients developed progressive disease during the first 5 weeks of treatment. We concluded that this regimen of IL-2 and IFN-alpha is ineffective.
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PMID:Interleukin-2 and interferon-alpha in the treatment of patients with advanced non-small-cell lung cancer. 132 67

Ninety-three collections of leucocytes by cytapheresis followed by separation of monocytes by centrifugal elutriation were undertaken in twelve metastatic cancer patients (four melanomas, six colon carcinomas, one ovarian carcinoma, and one lung cancer). The leucaphereses were performed aiming to collect a product, ready for introduction into the elutriation chamber, i.e., with low contamination by erythrocytes and granulocytes. The median collection of leucocytes was 7.3 x 10(9). After elutriation, purified monocytes (mean: 0.91 x 10(9)) were cultured with 3-5% autologous serum for 7 days in the presence of 250 IU/ml of recombinant human gamma-interferon (Rh-IFN gamma) for the last 18 h of culture. The median number of activated macrophages (MAK) available for reinfusion was 2.4 x 10(8) for each culture. The phenotypes and the antitumoral potentiality of MAK cells were documented. Reinfusions performed i.v. or i.p. were well tolerated with no major side effects. No complete tumor response was obtained. One partial response and two stabilizations of the disease were observed in one melanoma and two colon carcinomas.
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PMID:Adoptive immunotherapy with activated macrophages grown in vitro from blood monocytes in cancer patients: a pilot study. 151 25

Expression of class I and class II major histocompatibility complex antigens on a human small-cell lung cancer cell line and its multidrug-resistant variant was examined before and after exposure to interferon alpha (IFN alpha) and IFN gamma by flow cytometry. Neither IFN alpha nor IFN gamma induced class II antigen expression on the drug-sensitive or resistant cell line. Induction of class I antigen expression along with an inhibition of proliferation was observed in both cell lines after IFN alpha treatment. On the other hand, IFN gamma treatment resulted in growth inhibition and enhancement of class I antigen expression in the sensitive cell line but not the resistant cell line. The differential response of the two cell lines to IFN gamma cannot be directly attributed to the acquisition of drug resistance but it suggests that further investigation of the possibility that drug-sensitive and resistant small-cell lung tumors may respond differently to immunotherapies that include IFN gamma is warranted.
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PMID:Differential growth inhibition and enhancement of major histocompatibility complex class I antigen expression by interferons in a small-cell lung cancer cell line and its doxorubicin-selected multidrug-resistant variant. 171 27

Thirty-four patients with previously untreated advanced non-small-cell lung cancer were treated with a combination of polychemotherapy and recombinant interferon. Chemotherapy consisted of cyclophosphamide, 400 mg/m2, epidoxorubicin, 50 mg/m2, and cisplatin, 40 mg/m2 (CAP) i.v. on day 4; recombinant alpha 2b interferon (r alpha 2b IFN) was given i.m. daily at the dose of 3-5 MU from days 1 to 7. The treatment was repeated every 4 weeks. In the 32 eligible patients the overall response rate was 19.3% (95% C.L. 7.4-37.4%). Non-hematologic toxicity consisted formerly in flulike symptoms and fatigue complained of by 37.5% and 31.2% of patients, respectively, and vomiting reported in 68.7% of patients; grade III-IV myelotoxicity was observed in 12.5% of cases. In no case was the toxicity life threatening. The median overall actuarial survival and progression-free survival were 37 and 20 weeks, respectively. This study indicates that the combination of CAP chemotherapy and r alpha IFN is feasible and active in the treatment of advanced non-small-cell lung cancer.
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PMID:Combination chemotherapy and interferon alpha 2b in the treatment of advanced non-small-cell lung cancer. The Italian Lung Cancer Task Force (FONICAP). 185 86

Currently, three classes of interferon are used in the treatment of malignancies. Interferon-gamma is the best studied. Bone marrow suppression as well as immune hemolytic anemia have been described. Heretofore, only bone marrow suppression has been attributed to interferon-gamma (IFN gamma). In this report, we describe a woman with lung cancer being treated with IFN gamma in whom acute hemolytic anemia occurred. Immune hemolysis did not appear to be the cause. We concluded that in addition to bone marrow suppression, hemolysis should be considered in a patient receiving IFN gamma in whom an unexplained drop in hematocrit occurs.
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PMID:Hemolytic anemia in a cancer patient treated with recombinant interferon-gamma. 211 76

The antiproliferative and cytotoxic effects of purified IFN-alpha and recombinant IFN-gamma were investigated using both direct cell counting and a clonogenic assay on a panel of 5 established human lung cancer cell lines and for 2 of them also on their multidrug-resistant counterparts. There was considerable heterogeneity in the response of the cell lines to the IFNs in terms of growth inhibition. Clonogenic assay of IFN-treated cells indicated that, where a cell line had responded markedly to an IFN, only a small fraction of the cells remaining after IFN treatment were clonogenically viable. When cells were placed into the clonogenic assay in the presence of IFNs, the time course of colony formation was different from that seen in the control cultures for most of the cell lines. The measured "surviving fraction" was greatly dependent upon the time of colony counting. When the effects of IFNs in combination with ADM were studied, conclusions regarding the interaction of the effects of the agents also depended upon the time at which colonies were counted.
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PMID:The use of clonogenic assays in assessing the response of human lung cancer cell lines to alpha and gamma interferons alone or in combination with adriamycin. 211 86

This study was conducted to assess, by continuous exposure, the inhibitory effects of rH-TNF and rH-IFN-alpha, -beta and -gamma, either alone or in combination, on the colony formations of human lung cancer cell lines. The cell lines tested were PC-7 and PC-9 (adenocarcinoma), PC-10 (squamous cell carcinoma) and PC-13 (large cell carcinoma). Additional experiments were performed with L929 (transformed murine fibroblast), because of its known high sensitivity to TNF. rH-TNF inhibited the colony formations of PC-10 and L929 even at a low concentration (10 U/ml). However, PC-7, PC-9 and PC-13 were resistant to rH-TNF. rH-IFN-alpha, -beta and -gamma inhibited the colony formation of PC-10 (less than 50% of control) at the highest concentration tested (10(4) U/ml), but only rH-IFN-beta inhibited that of PC-7. PC-9, PC-13 and L929 were insensitive to all three rH-IFNs, even at the highest concentrations tested. Combination effects of rH-TNF and rH-IFN-alpha or -gamma were synergistic only at the highest concentration combinations tested in PC-9. However, the maximum inhibition of colony formation of PC-7, PC-9 or PC-13 in any concentration combination treatment was less than 50%.
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PMID:Colony inhibitory effect of recombinant human tumor necrosis factor (rH-TNF) and/or recombinant human interferon (rH-IFN)-alpha, -beta and -gamma on human lung cancer cell lines. 243 30

Human lung cancer that induced marked granulocytosis in both the patient and tumor-transplanted nude mice (G2 mice) and from which conditioned medium (G2-T-CM) exhibited human and mouse active colony-stimulating activity (CSA) has been reported (K. Ikeda et al. Cancer Res 1985; 45:4144-4249). Recently, we found differentiation-inducing activity (DIA) in G2-T-CM, which differentiated human promyelocytic leukemic cells (HL-60) to macrophage-like cells. Differentiated HL-60 cells were considered to be mature macrophages as judged by the positivity of butyrate esterase activity, the acquisition of Fc receptor, and the increment in capacity of phagocytosis and nitroblue tetrazolium reduction. The DIA in G2-T-CM was not attributed to interferons known to have DIA, because interferon activity was not found in G2-T-CM by bioassay (less than 4 U/ml) and by radioimmunoassay for gamma-IFN (less than 0.1 U/ml). Molecular weight of DIA was 36,000 Da and separated from CSA of which molecular weight was 22,000 Da by gel filtration on Sephadex G-150. DIA and CSA were also separated on chromatofocusing chromatography, because isoelectric point of DIA was mainly less than 4.0 and that of CSA was 4.3-5.7. This DIA was stable after heat treatment (56 degrees C for 30 min or 100 degrees C for 10 min) and in acidic condition (pH 2.0 for 24 hr). G2-T-CM is a good source of differentiation-inducing factor for further purification and molecular cloning.
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PMID:Human colony-stimulating factor-producing lung cancer tissue releases a differentiation-inducing factor for human leukemic cells. 244 32

The growth inhibitory effects of interferons, IFN-alpha and IFN-gamma on human lung cancer cell lines were studied using both a tetrazolium (MTT) colorimetric assay and direct cell counting. Significant discrepancies between the two assays were observed, the MTT assay consistently underestimating the growth inhibitory effects of the IFNs. There was no direct chemical effect of the IFNs on the tetrazolium reduction process. IFN treated cells showed increased cell size compared with control cells, although there was little or no change in cell cycle distribution. Mitochondrial activity was 30-50% greater in IFN-gamma treated cells (COR-L23) than the controls. Reduced formazan production per cell was observed in medium which had supported cell growth for several days. Differential 'medium conditioning' led to a difference in formazan production per cell between IFN and control cells and this was the major basis of the observed discrepancy. This discrepancy was not due to the differences in the glucose concentrations between these media. However, differences in pH between the media proved to be the major contributory factor of the discrepancy.
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PMID:The MTT assay underestimates the growth inhibitory effects of interferons. 252 90

The effect of cloned human interferon-alpha (IFN-alpha) on the expression of HLA-ABC antigens (HLA-ABC) and beta 2-microglobulin (beta 2m) on human peripheral lymphoid cells in vivo was studied by cytofluorometry using monoclonal antibodies and fluorescein-labelled rabbit anti-mouse immunoglobulin. A significant increase in the mean fluorescence intensity of HLA-ABC (median 59%, P less than 0.001) and beta 2m (median 57%, P less than 0.001) on small lymphoid cells was observed 24 h after initiation of IFN-alpha treatment (50 X 10(6) units IFN-alpha/m2 three times a week). The enhanced expression of these antigens in vivo was found in 11 of 12 examined patients with primary bronchial carcinoma. A concomitant increase in serum beta 2m (median 90%, P less than 0.001) was found in all patients. In contrast the amount of cell-associated HLA-ABC and beta 2m remained unchanged (P greater than 0.1 and P greater than 0.5, respectively) by day-to-day analysis of an untreated healthy control group. An increased expression of both HLA-ABC (mean 55%, P less than 0.0005) and beta 2m (mean 23%, P less than 0.01) was also observed prior to treatment in the lung cancer patients when compared to a group of age matched healthy individuals. Treatment with IFN-alpha caused a significant redistribution of mononuclear cells resulting in both absolute and relative lymphopenia. Pre-treatment lymphocyte counts were 1.09 X 10(9)/1 (range 0.49-1.73), post-treatment counts were 0.55 X 10(9)/1 (range 0.39-1.06).
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PMID:Enhanced expression in vivo of HLA-ABC antigens and beta 2-microglobulin on human lymphoid cells induced by human interferon-alpha in patients with lung cancer. Enhanced expression of class I major histocompatibility antigens prior to treatment. 298 11


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