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 effect of human recombinant leukocyte interferon A (IFN-alpha A) and DL-alpha-difluoromethylornithine (DFMO) as single drugs and in combination on the in vitro growth, cell cycle distribution, activity of the enzyme L-dopa decarboxylase, and expression of the c-myc and N-myc oncogenes was studied in human lung cancer cell lines. In vitro growth activities were tested in concentrations ranging from 10 to 50,000 IU/ml for IFN-alpha A and from 0.1 to 10 mM for DFMO by means of the soft agarose clonogenic assay using continuous drug exposure. Ten well established small cell lung cancer (SCLC) cell lines including five cell lines of the classic and five of the variant phenotype, two cell lines derived from adenocarcinoma of the lung, and one large cell lung cancer cell line were included in the study. We found that IFN-alpha A inhibited the growth only of the variant phenotype of SCLC with an approximate drug concentration yielding a 50% inhibition of colony growth of 1000 IU/ml. None of the SCLC classic cell lines was inhibited significantly. The growth inhibition of IFN-alpha A correlated with the proliferation rate of the tumor. IFN-alpha A inhibited one of two adenocarcinoma cell lines and 0 of 1 large cell lung cancer cell line. DFMO inhibited the colony formation of 10 of 10 SCLC cell lines, 2 of 2 adenocarcinoma cell lines, and 0 of 1 large cell lung cancer cell line with a drug concentration yielding a 50% inhibition of colony growth of 1 mM. No difference between the classic and variant phenotypes of SCLC was found. The combination of IFN-alpha A and DFMO resulted in an additive cytostatic effect in all cell lines tested. The same result, i.e., an additive cytostatic effect, was obtained for two SCLC cell lines that were tested in liquid culture. Neither single drugs nor their combination led to an accumulation of cells in a particular phase of the cell cycle nor did it affect the activity of the SCLC classic marker enzyme L-dopa decarboxylase. In addition, IFN-alpha A, DFMO, and their combination did not affect the expression of the c-myc and N-myc oncogenes in cell lines NCI-N417 and NCI-H526, respectively, following 4, 24, and 72 h of continuous drug exposure.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Additive and differential biological activity of alpha-interferon A, difluoromethylornithine, and their combination on established human lung cancer cell lines. 308 22

Hundred and fifty-four samples of heparinized blood from patients with chronic toxoplasmosis, chronic brucellosis, lung diseases, psychiatric affective disorders, healthy individuals and neonates, were obtained. The experimental material included also 14 bone marrow samples from patients with hematological diseases or lung cancer. The whole cell populations were treated with several classical IFN inducers and supernatants were assayed for IFN activity in human lung adenocarcinoma cell line A 549 using VSV or EMC viruses as challenge. The response of WBC to NDV or PHA + PMA was high and remarkably stable in majority of cases except listed below. The levels of IFN induced by LPS were low. The response of WBMC to IFN inducers closely resembled the response of WBC. Low IFN levels in samples of stimulated WBMC from some hematological patients were connected with low cellularity. WBC from psychiatric patients with affective disorders weakly responded to stimulation with NDV. This suggested an existence of deficiency of IFN alpha production connected with affective disorders. Also WBC from cord blood failed to react to PHA + PMA and were poorly responsive to NDV.
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PMID:Assessment of interferon production in patients with chronic nonviral diseases by whole blood or whole bone marrow techniques. 315 Jun 55

During a phase II trial of recombinant IFN-alpha given in doses of 50 X 10(6) units/m2 three times per week to lung cancer patients, 13 patients were evaluated longitudinally in NK and ADCC assays and in immunofluorescence tests enumerating the number of cells reactive with the new N901 NK-cell antibody. An increase in NK-cell activity could be demonstrated when values before and 24 h after the first injection of IFN were compared, but simultaneously the enhancing effect of IFN-alpha on NK-cells added to in vitro cultures was abolished, probably as a result of preactivation of NK cells in vivo. After 2-4 weeks of treatment, the majority of patients exhibited a pronounced decrease in NK-cell activity while still retaining the inability to be boosted by IFN added in vitro. Investigations with the NK antibody N901 showed that the initial increase in NK activity appeared concomitantly with an increase in the number of N901 positive cells, indicating that the mechanism behind this increase was an increase in the number of circulating NK cells. In contrast, the decrease in NK activity mentioned above was not followed by a similar decrease in the number of N901+ cells, and it was concluded that this decrease might be attributable to either an exhaustion phenomenon or to an induction of a refractory state of peripheral blood NK cells. When measuring ADCC activity, increases in lytic activity were seen only in patients in whom they could be attributed to non-IgG-dependent (NK-like) mechanisms. These data are discussed in relation to other clinical trials using leukocyte or recombinant IFN-alpha.
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PMID:Effect of recombinant alpha interferon on NK and ADCC function in lung cancer patients: results from a phase II trial. 609 85

Pleural effusions and sera of two patients with lung cancer were tested after intrapleural injection of OK-432 as an anticancer drug for IFN-alpha activity by biological assay and for IFN-alpha as an antigen by radioimmunoassay. The titers by radioimmunoassay were fairly consistent with those by biological assay, but were usually higher. In Case 1, IFN-alpha was observed fairly early after administration of OK-432 and only in pleural effusions. In Case 2, induction of IFN-alpha at low level was observed late after the first administration of OK-432 both in the pleural effusion and serum and was detected only by radioimmunoassay.
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PMID:Interferon-alpha in serum and carcinomatous pleural effusion after repeated intrapleural injections of antitumor agents. 631 25

Clonogenic tumor cells from fresh biopsies of human cancers were cultivated in vitro and tested for sensitivity by continuous exposure to pharmacologically achievable concentrations of either of two highly purified human leukocyte interferon subtypes (IFN-alpha A and IFN-alpha D) prepared by recombinant DNA methods. The interferons were compared on a weight basis at concentrations of 0.4 and 4.0 ng/ml (equivalent to 80 and 800 units of interferon activity for IFN-alpha A and 2.0 and 20 units for IFN-alpha D). Inhibition of tumor colony-forming units (50% of control or less) was observed in 38.1% of the 273 tumors tested against IFN-alpha A, and in 16% of the 71 tumors tested against IFN-alpha D. Of the tumor types with at least ten samples tested against IFN-alpha A, the percentage of cases exhibiting inhibition was as follows: melanoma (51.7%), lung cancer (50%), myeloma (33.4%), ovarian cancer (33.9%), sarcoma (33.3%), adenocarcinoma of unknown primary (30.4%), breast cancer (28%), acute leukemia (30.8%), and renal cancer (23%). More marked inhibition (30% of control or less) was observed in 18.7% of all tumors tested against IFN-alpha A. Of 60 melanomas tested, 18 (30%) exhibited marked in vitro inhibition of growth with IFN-alpha A. Although a smaller number of tumors (71) were tested against IFN-alpha D on a weight basis, it appeared, in general, to be slightly less active than IFN-alpha A (p less than 0.01), and only 8% of tumors tested exhibited marked inhibition over the same dosage range of interferon. Comparison of the dose-response curves for the 68 tumors tested simultaneously against both interferons did not reveal marked interpatient differences in the inhibition curves, although IFN-alpha D was slightly less active overall. Tumors exhibiting at least 50% inhibition of tumor colony formation also proved to be sensitive to a significantly larger number of cytotoxic drugs (tested simultaneously) than the tumors not inhibited with interferon (p less than 0.0001 for IFN-alpha A). We conclude that the in vitro clonogenic assay may aid in targeting tumor types most likely to exhibit interferon sensitivity and assist in case selection for entry into clinical trials with cloned interferons.
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PMID:Effects of cloned human leukocyte interferons in the human tumor stem cell assay. 668 47

The constant increase of lung cancer incidence is confronted with the relatively low efficacy of drug therapy in patients with advanced stages of this disease. According to results of phase II studies interferon-alpha (IFN-alpha) monotherapy used as palliative measure is ineffective in all histological types of lung cancer. However, in certain therapy settings IFN-alpha has some efficacy. In small cell lung cancer IFN-alpha therapy, when given as maintenance following chemo- and/or radiation therapy-induced remissions, has shown some clinical benefit as documented by a prolongation of remission-free intervals. In patients with advanced non-small cell lung cancer and especially of the squamous cell type the combination of IFN-alpha with cisplatinum achieved remissions in about 45%. The efficacy of locoregional administration, i.e. intrapleural, in patients with malignant effusions is currently under investigation.
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PMID:[Interferon therapy of the lung and locoregional therapy in pulmology]. 750 89

Interstitial deletions of the short arm of chromosome 9 are associated with glioma, acute lymphoblastic leukemia, melanoma, mesothelioma, lung cancer, and bladder cancer. The distal breakpoints of the deletions (in relation to the centromere) in 14 glioma and leukemia cell lines have been mapped within the 400 kb IFN gene cluster located at band 9p21. To obtain information about the mechanism of these deletions, we have isolated and analyzed the nucleotide sequences at the breakpoint junctions in two glioma-derived cell lines. The A1235 cell line has a complex rearrangement of chromosome 9, including a deletion and an inversion that results in two breakpoint junctions. Both breakpoints of the distal inversion junction occurred within AT-rich regions. In the A172 cell line, a tandem heptamer repeat was found on either side of the deletion breakpoint junction. The distal breakpoint occurred 5' of IFNA2; the 256 bp sequenced from the proximal side of the breakpoint revealed 95% homology to long interspersed nuclear elements. One- and two-base-pair overlaps were observed at these junctions. The possible role of sequence overlaps, and repetitive sequences, in the rearrangement is discussed.
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PMID:Breakpoint junctions of chromosome 9p deletions in two human glioma cell lines. 752 63

The FONICAP group is screening, with randomised phase II studies, the activity of new chemotherapy programmes for advanced non-small-cell lung cancer (NSCLC) looking for regimens with > 30% activity. In the present study, three regimens were tested: MIP (mitomycin 6 mg m-2, ifosfamide 3 g m-2, cisplatinum 80 mg m-2 on day 1 every 28 days); MIP-IFN (MIP and interferon alpha-2b 3 MU s.c. three times a week); and PC (cisplatinum 60 mg m-2 and carboplatin 400 mg m-2 on day 1 every 28 days). Overall 93 chemotherapy-naive patients were enrolled: 23 received MIP, 27 received MIP-IFN and 43 received PC. Eighty per cent of the patients had stage IV and 20% stage IIIb disease (positive pleural effusion or supraclavicular nodes). Response rates were as follows: MIP = 9% (95% CI 1-28%), MIP-IFN = 7% (95% CI 1-24%) and PC = 14% (95% CI 5-28%). The overall median survival was 183 days. Grade III-IV leucopenia was observed in 36% of patients treated with MIP-IFN vs 10% in the other two arms, and thrombocytopenia grade III-IV was reported in nearly 10% of patients overall. In conclusion, (1) all three regimens investigated have poor activity (< 30%); (2) when tested in multicentre randomised phase II trials, MIP displays lower activity than in phase II trials; (3) PC has similar activity to other platinum-containing regimens; (4) randomised phase II studies are a reliable and quick method of determining the anti-tumour activity of novel chemotherapeutic regimens in NSCLC.
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PMID:Mitomycin-ifosfamide-cisplatinum (MIP) vs MIP-interferon vs cisplatinum-carboplatin in metastatic non-small-cell lung cancer: a FONICAP randomised phase II study. Italian Lung Cancer Task Force. 752 22

In order to select a suitable combination chemotherapy with BOF-A2 from the view of both anti-tumor effect (IR) and decrease of side effect, we studied a combination significance of BOF-A2 with CPT-11 that promised for a new anticancer drug, CDDP or mitomycin C (MMC) that used widely to many cancer patients and interferon-alpha (IFN-alpha) against colon, stomach and renal cancer, respectively, by using xenografted nude mice. The combination therapy of BOF-A2 with CDDP was effective against stomach cancer (H-111) from the cellular change and decreased side effect. The combination therapy of BOF-A2 with MMC showed additive effect against stomach cancer (H-111) from IR and cellular changes. The combination effect of BOF-A2 with IFN-alpha was additive and synergistic against renal cancer (H-12). The combination therapy with CPT-11 was effective (IR > or = to 58%) from antitumor effect, additive from IR and synergistic from cellular change against lung cancer (H-74) and colon cancer (H-110), to which conventional drugs were generally insensitive and spontaneously tolerant. BOF-A2 was expected to be a promising new anti-cancer agent in the future clinical trial.
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PMID:[Combination chemotherapy of BOF-A2, a new 5-FU derivative, with various anticancer agents against human cancer xenografts in nude mice]. 806 Jan 37

A Phase I trial was conducted to investigate the clinical toxicity, pharmacokinetics, and chemiluminescence (CL) responses of alveolar macrophages (AMs), peripheral blood neutrophils, and monocytes after subcutaneous injection of recombinant interferon-gamma (rIFN-gamma). Six patients with lung cancer received rIFN-gamma subcutaneously as single doses of 0.2, 0.6, and 1.8 mg. Bronchoalveolar lavage was performed three times: 21 h before as well as 6-7 and 27 h after injection. Serum samples were taken five times during the 27-h follow-up. IFN concentrations were measured from alveolar epithelial lining fluid (ELF) and serum by using an antiviral bioassay. IFN-gamma was not detectable in ELF after subcutaneous injection. AMs did not effect an increase in CL responses to N-formyl-methionyl-leucyl-phenylalanine or to phosphate-buffered saline. Circulating IFN-gamma was detectable at 3-12 h after an injection of 1.8 mg of rIFN-gamma, the highest dose given. CL responses of peripheral blood monocytes increased in all patients after injection, whereas the responses of neutrophils were less clear-cut. All patients developed systemic side effects such as transient fever, nausea, headaches, and flu-like symptoms. The findings suggest that rIFN-gamma passes poorly from the blood to the pulmonary alveoli. On the basis of this and our previous findings of increased CL responses in AMs and measurable IFN concentrations in ELF after inhalation of rIFN-gamma, we recommend inhalation rather than the parenteral route of IFN-gamma for the treatment of respiratory diseases.
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PMID:Subcutaneously administered recombinant interferon-gamma in humans: pharmacokinetics and effects on chemiluminescence responses of alveolar macrophages, blood neutrophils, and monocytes. 806 1


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