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)

Eighty one patients (59 females, 22 males) with advanced solid tumors were treated with Adriamycin in doses of 40 mg/m2 body surgace daily, in two days cycles, with resting periods of 3 weeks. Overall response rate was 46% (37/81). In breast cancer response rate was 56% (13/23) and in ovarian cancer 48% (13/27). In various other tumors remission was observed in soft tissue sarcomas (3/8), thyroid cancer (1/7), osteogenic sarcoma (1/4), oesophageal cancer (2/4), lung cancer (2/4), bladder cancer (1/2) and hepatoma (1/2). In breast cancer patients, 2-7 month remission duration was observed (M equal to 4.5 month) and in ovarian cancer 1.5-5 month (M equal to 3.2 month). Adriamycin was also applied intrapleurally in 31 patients with malignant pleural effusions with a low response rate (26%). This modified schedule of Adriamycin administration showed a high antitumor activity in breast and ovarian cancer and in soft tissue sarcomas. Squamous cell carcinoma of the esophagus was also sensitive to Adriamycin therapy. The very low rate of myelosuppression and oral ulceration showed the decreased toxicity of this Adriamycin administration schedule.
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PMID:Modified administration schedule of adriamycin in solid tumors. 14 May 42

Adriamycin has not been as extensively evaluated in Japan as in some other countries. This is due both to the widespread use of mitomycin C and importantly to the alopecia caused by adriamycin being particularly disturbing to Japanese patients. Japanese studies have shown the drug to be highly active in tumors such as stomach cancer (31/92), lung cancer (27/84), and malignant lymphomas (15/46). Combination studies have been mainly with 5-FU although others have also been investigated. Other approaches which have been studied include intraarterial infusion, local application in bladder cancer, intrapleural application and in the treatment of childhood malignancies.
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PMID:Clinical aspects of adriamycin in Japan. 70 10

Adriamycin (40 mg/m2 i.v., on day 1) plus cyclophosphamide (200 mg/m2 orally, day 1 to 5) were given to 23 patients with advanced lung cancer. Administration cycles were repeated every 3 weeks. No patient had been previously treated with chemotherapy, 5 received prior radiotherapy. Objective improvement was observed in 7 patients, partial remission was observed in 3. The median duration of response was 2 months.
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PMID:Adriamycin plus cyclophosphamide in advanced bronchial carcinoma. 102 44

Adriamycin is a new anticancer antibiotic with a wide spectrum of activity against solid tumours. The results obtained with this agent in 159 patients with histologically confirmed advanced metastastic malignancies are reported. Encouraging results were obtained in patients with sarcomas of bone and soft tissue (12/22). Response was also seen in mesothelioma (3/9) and lung cancer (5/15). A variety of other neoplasms was also treated and results obtained in neuroblastoma, testicular tumours, stomach carcinoma, breast cancer and nephroblastoma are reported. Treatment is discussed, with reference to response rates and toxicity. Results in 72 patients with advanced breast cancer, who received adriamycin in combination with other chemotherapeutic agents, are presented. Seventeen patients with primary liver cancer were also treated with adriamycin. To date, this is the only chemotherapeutic agent that appears to significantly improve survival times in patients with this resistant form of cancer. The prophylactic use of adriamycin against osteogenic sarcoma is also discussed.
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PMID:Adriamycin in the treatment of cancer. 125 Dec 78

The National Cancer Institute has instituted a primary screening system for testing new agents against cultured cancer cell lines. The purpose of this study was to determine the feasibility of using a nude rat orthotopic (organ-specific) human lung cancer model system as an in vivo secondary screen for general evaluation of new anticancer agents and therapies active against lung cancer. To make this determination, we tested whether this system allows measurement of uptake and tumoricidal activity of anticancer therapies. Tumor-bearing lungs from 53 Rowett nude rats with orthotopically implanted human large-cell undifferentiated lung carcinoma (NCI-H460) were perfused ex vivo for 1 hour with or without each of two anticancer modalities. Lungs were perfused with blood-free perfusate alone (untreated control), perfusate with 100 micrograms/mL doxorubicin (treated positive control), or perfusate with lymphokine-activated killer cells plus human recombinant interleukin-2 (LAK/rIL-2). Weight gain during perfusion was the criterion used to quantitate lung injury. Treatment efficacy was measured by clonogenic assay after enzymatic disaggregation of the perfused tumors. Doxorubicin levels in the tumor and in the uninvolved lung were measured by high-performance liquid chromatography. Both treatment groups showed only slight increases in lung weight compared with that in the untreated control group, suggesting good lung tolerance of the procedure. Lung and tumor levels of doxorubicin were 320 +/- 21 ng/mg of tissue and 32 +/- 5 ng/mg of tissue (means +/- SE), respectively. Clonogenic assay demonstrated a fivefold to 10-fold reduction in the surviving fraction of tumor cells with doxorubicin but no change with LAK/rIL-2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Secondary screening system for preclinical testing of human lung cancer therapies. 131 Jul 46

Doxorubicin is one of the most potent drugs for the treatment of small cell lung cancer (SCLC), but less potent for non-small eell lung cancer (NSCLC). The prevalent use of doxorubicin is limited by the development of cardiomyopathy. Therefore, TUT-7 SM-5887, and ME2303 have been under the clinical studies to find new anthracyclines with less cardiotoxicity and higher therapeutic indices not only for SCLC but also for NSCLC. The dose-limiting factor of these drugs determined in phase I studies was leukocytopenia. Phase II studies which are currently under way have indicated that SM-5887 is possibly most potent for the treatment of NSCLC, and that these drugs have less cardiotoxicity compared to the mother compound, doxorubicin.
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PMID:[New anthracycline analogues in the treatment of lung cancer]. 133 24

Multidrug resistance can be induced in mammalian cells by selection with a single cytotoxic agent. Overproduction of the energy-dependent drug efflux pump P-glycoprotein, encoded by the mdr1 gene, has been identified as the cause of one form of multidrug resistance. The molecular basis of other forms of multidrug resistance is unknown. Doxorubicin selection of the human squamous lung cancer cell line SW-1573 resulted in multidrug-resistant sublines in which a non-P-glycoprotein-mediated form of multidrug resistance precedes mdr1 expression. Here we present a cytogenetic analysis of both non-P-glycoprotein-mediated multidrug-resistant and P-glycoprotein-mediated multidrug-resistant sublines derived from SW-1573. Three independently derived non-P-glycoprotein-mediated multidrug-resistant sublines showed a heterozygous deletion of the short arm of chromosome 2 (p23-pter), whereas alterations of chromosome 7 were present in the P-glycoprotein-mediated multidrug-resistant cell lines. In one series of clonally derived P-glycoprotein-mediated multidrug-resistant sublines, mdr1 overexpression was accompanied by various markers of chromosome 7 with breakpoints at 7q22, the mdr1 gene being known to be located at 7q21.1. Our data suggest that in SW-1573 cells acquisition of non-P-glycoprotein-mediated multidrug resistance is accompanied by a specific deletion or a translocation involving the short arm of chromosome 2, whereas in the emergence of P-glycoprotein-mediated multidrug resistance a rearrangement of the long arm of chromosome 7 is a critical event.
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PMID:Cytogenetic alterations associated with P-glycoprotein- and non-P-glycoprotein-mediated multidrug resistance in SW-1573 human lung tumor cell lines. 135 3

A series of analogues of the antitumor alkaloids ellipticine and olivacine were tested for cytotoxicity against four human lung cancer cell lines: H69, N417, H460, and H358. Adriamycin (doxorubicin), ellipticine, olivacine, and celiptinium were used as standards. Adriamycin was cytotoxic at 2 microM and celiptinium was inactive at the highest concentrations tested (IC50 > 48 microM). N-methylcarbamates of 9-methoxy-6H-pyrido[4,3-b]carbazole 1-,5-, and 11-methanols gave IC50 values ranging from 0.02 to 0.11 microM against N417, H460, and H358 and were only slightly less effective against H69.
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PMID:N-methylcarbamate derivatives of ellipticine and olivacine with cytotoxic activity against four human lung cancer cell lines. 147 85

Liposome entrapment of doxorubicin has been shown to reduce its cardiotoxicity in vivo and increase its therapeutic index. A further improvement in therapeutic index could be achieved through targeting of liposome-entrapped drug selectively to cancer cells. Monoclonal antibodies against the squamous lung cancer cell line KLN-205 have been ligated to the surface of long-circulating (Stealth) and conventional liposomes. The antibody-bearing liposomes showed specific, competitive uptake by KLN-205 cells as compared to liposomes bearing nonspecific isotype-matched antibodies or antibody-free liposomes. Doxorubicin-containing antibody-liposomes resulted in as much as a 15-fold decrease in the 50% inhibitory concentration for doxorubicin against KLN-205 cells as compared to free doxorubicin or doxorubicin entrapped in antibody-free liposomes.
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PMID:Antibody-mediated specific binding and cytotoxicity of liposome-entrapped doxorubicin to lung cancer cells in vitro. 151 45

Doxorubicin (Dox) was coupled by four published methods to a murine monoclonal antibody (MAb) developed against human pulmonary adenocarcinoma. Dox immunoconjugates made with this murine IgG1 MAb, 44-3A6, were evaluated for anti-tumor activity against the human lung cancer cell line, A549. Dox was attached to the MAb (1) by an oxidized dextran T40 intermediate, (2) using dilute glutaraldehyde cross-linking, (3) with an acid-sensitive linker using cis-aconitic anhydride and EDCI, a water-soluble carbodiimide, and (4) using EDCI alone. The biological activity of the different conjugates was compared in vitro by antigen binding (whole-cell RIA) versus serial dilutions of unconjugated MAb cytotoxicity (dye exclusion/viability) versus long dilutions of the various Dox conjugates, Dox and mixtures of Dox and MAb. Preincubation of antigen-expressing tumor cells (A549) for 2 h with excess (250 micrograms/ml) unconjugated MAb prior to conjugate exposure was attempted in order to block the cytotoxic effect. The number of Dox molecules conjugated to 44-3A6 (molar incorporation ratio or MIR) ranged from 3 to 10/1 for carbodiimide linkage and up to 63/1 using the dextran intermediate. Cis-aconityl-derivatized Dox conjugates contained an average of 22 mol Dox/mol immunoglobulin, but drug incorporation was quite variable from experiment to experiment. Dilute glutaraldehyde cross-linking produced an average MIR of 10/1. After repeated attempts to minimize drug and/or MAb precipitation, the percentage decrease (versus MAb) in immunoreactivity of the drug conjugates ranged from 2 to 42% and was dependent on the coupling method and extent of aggregate formation in the preparation. Loss of biological activity (antigen binding and cytotoxicity) was significant when aggregation and precipitation occurred. There were additional losses (17-25%) after sterile filtration through low protein-binding (0.22 microns) filters. Immunoconjugates produced by glutaraldehyde cross-linking were reproducibly 5-10 times more potent against antigen-bearing tumor cells than Dox, and showed selectivity for inhibiting the viability of antigen-positive A549 cell line. Noncovalent mixtures of 44-3A6 and Dox were slightly more potent than Dox. Immunoconjugates produced by the aconityl method and the dextran intermediates were less effective than Dox, the glutaraldehyde-mediated conjugates or Dox and 44-3A6 mixtures. The unconjugated MAb was not cytotoxic when tested at concentrations up to 500 micrograms/ml. Blocking studies using 'cold', unlabeled MAb were of limited success.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Monoclonal antibody 44-3A6 doxorubicin immunoconjugates: comparative in vitro anti-tumor efficacy of different conjugation methods. 165 54


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