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)

Selected immunotherapies (tumor necrosis factor, interleukin-1, interleukin-2, and gamma interferon), chemotherapeutic agents (mitomycin, platinum, doxorubicin [Adriamycin], and bleomycin), and radiation therapy have been described to exert cytotoxicity through the generation of reactive oxygen species, including superoxide and hydrogen peroxide. Tumor necrosis factor, however, has been shown to impart increased resistance in vitro and in vivo against reactive oxygen species stress, including radiation therapy and oxygen toxicity, possibly because of the induction of increased cellular buffering capacities. It is unknown whether the sensitivity of a lung cancer cell to reactive oxygen species therapy is altered by tumor necrosis factor through the induction of free radical scavenging enzymes such as manganese superoxide dismutase. This question was investigated as follows: A549 lung adenocarcinoma cells, exposed for 24 hours to 0, 0.1, 1.0, or 10 micrograms/ml concentrations of tumor necrosis factor, were exposed to hypoxanthine plus xanthine oxidase, a superoxide generating system, for varying intervals. The number of cells surviving 5 days after the stress was determined, and cells exposed to tumor necrosis factor were examined by Northern Blot analysis for induction of the manganese superoxide dismutase gene. The hypoxanthine-xanthine oxidase stress alone caused a time-dependent decrease in survival; however, pretreatment with tumor necrosis factor increased cell survival significantly. Moreover, the cells exposed to tumor necrosis factor had a fivefold increase in the number of manganese superoxide dismutase transcripts. These findings suggest that tumor necrosis factor may confer resistance of lung cancer cells to subsequent reactive oxygen species-based therapies, and the resistance of these cells may be due to increased expression of manganese superoxide dismutase. Clinical treatment failures may result, especially if tumor necrosis factor is given concurrently with other therapies.
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PMID:Tumor necrosis factor-alpha alters response of lung cancer cells to oxidative stress. 196 Sep 95

We established an etoposide (VP-16)-resistant human small-cell lung cancer cell line (H69/VP) by stepwise exposure to VP-16. The resistance of H69/VP to VP-16 was 9.4-fold that of the parent cell line (H69/P). H69/VP showed cross-resistance to Adriamycin (ADM), (4S)-4,11-diethyl-4-hydroxy-9-[(4-piperidinopiperidino) carbonyloxy]-1H-pyrano[3',4':6,7]indolizino [1,2-b]quinoline-3,14(4H,12H)-dionehydrochloride trihydrate (CPT-11), teniposide (VM-26), vindesine (VDS) and vincristine (VCR). The amount of DNA topoisomerase II (topo.II) was nearly the same in H69/P and H69/VP cells. The catalytic activity of topo.II in H69/VP cells was lower than that in the H69/P line. Accumulation of [3H]-VP-16 in H69/VP was 6.1-7.5 times lower than that in H69/P. According to Northern blot analysis, the mdr-1 mRNA level in H69/VP was markedly higher than that in H69/P. These findings suggest that H69/VP has a typical multidrug resistance (MDR) phenotype and that alteration of the drug accumulation mediated by P-glycoprotein may play an important role in resistance to VP-16. Reduced topo.II activity may also be associated with VP-16 resistance.
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PMID:Characterization of an etoposide-resistant human small-cell lung cancer cell line. 197 50

The Goldie-Coldman model explaining the kinetics of tumor cell kill and drug resistance has a potential application in designing chemotherapy regimes. In this Southwest Oncology Group (SWOG) trial we tested the alternation of two potentially noncrossresistant drug combinations with a concurrent drug combination in patients with limited small-cell lung cancer. The concurrent drug combination consisted of etoposide (VP-16), 75 mg/m2/intravenously (IV), days 1, 2, and 3; vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), 40 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (EVAC). The alternating combination consisted of VP-16, 100 mg/m2/IV, days 1, 2, and 3; and cisplatin (CDDP), 100 mg/m2/IV, day 1, alternating with vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin, 50 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (VP-16/CDDP-VAC). Chemotherapy was administered at 3-week intervals for six cycles both before and after chest (5,000 rads/5 weeks) and whole brain radiotherapy (3,000 rads/2 weeks). One hundred ninety-nine patients received EVAC and 201 received the alternating combination. There was no significant difference in the response rate to the initial six cycles of treatment with EVAC (CR, 40%) versus the alternating combination (CR, 38%). There was no significant difference between the best response, EVAC (CR, 48%) and VP-16/CDDP-VAC (CR, 51%). Median survival for all randomized patients on EVAC is 15.1 months versus 16.5 months on the alternating combination (P = .58). Toxicities consisted primarily of bone marrow suppression, anorexia, nausea and vomiting, peripheral neuropathies, and alopecia. As in previous trials, the chest was the most common site of relapse (33%). There were no differences in the incidence and sites of relapse between the two treatment arms. These treatments appear equally effective at inducing remission and prolonging survival in patients with small-cell lung cancer.
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PMID:Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study. 215 94

A combination phase II study was performed on 31 patients with previously untreated small-cell lung cancer (19 LD & 12 ED). Patients were treated intravenously with Adriamycin (30 mg/m2 day 1), CDDP (80 mg/m2 day 1) and Etoposide (70 mg/m2 x 3 day 1, 3, 5). This combination chemotherapy was administered over a four- or five-week period. Among 26 evaluable patients there were 4 CR and 17 PR, giving a response rate of 80.8% (68.4% in LD). The median duration of response was 19 (3-123) weeks. Despite the relatively low response rate and CR rate, the median survival times of LD and ED patients were 17.0 (3.1-43.1) and 9.4 (4.4-17.7) months, respectively. The major toxic effect of this regimen was bone marrow suppression. Two patients were excluded from this study in the first course because of severe hematologic toxicity. The renal toxicity of this regimen was minimal and no patients developed any clinical problem. Nausea and vomiting during the treatment were well controlled by high-dose metoclopramide and methylprednisolone. In conclusion, this combination of chemotherapy is effective for patients with small cell lung cancer. However, the advantage of adding Adriamycin to CDDP and Etoposide is still controversial.
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PMID:[A combination phase II study of adriamycin, CDDP and etoposide in small cell lung cancer]. 215 85

We examined the quality of life in the arterial infusion chemotherapy of hepatocellular carcinoma patients using a questionnaire. The questionnaire used a category scale method of five grades. The questions about the quality of life covered ten areas for investigation (appetite, discomfort pain, nausea, daily activities, sleep, fatigue, time with family and friends, thinking about illness and confidence in the treatment). We added up scale points after one week and those after two weeks after the treatment. Patients after one-shot infusion showed aggravated scale points of anorexia and discomfort. Patients after transcatheter arterial embolization showed scale points of abdominal pain, general fatigue and discouragement about illness. Scale points in matters of thinking about illness and confidence in the treatment informed us about confidence in the course of treatment and comprehension of illness by cancer patients. How do we measure the quality of our care? This is difficult, but we thought the rate of being at home in survival might furnish us with much information in respect to the treatment and the quality of our care. In 36 patients with hepatocellular carcinoma treated with transcatheter arterial infusion and embolization, the arithmetic mean survival time after treatment was 412.1 days and time at home was 305.6 days. The rate of being at home doing survival time was 74.2% after the arterial infusion chemotherapy in 39 patients. The rate of being at home in 9 cases with one-shot infusion of Adriamycin was 43.5% (111 days); that in 9 cases with infusion of Mitomycin C microcapsules was 86.6% (716 days); that in 17 cases with transcatheter arterial embolization using spongel was 72.0% (234 days),; and that in 4 cases with infusion using implantable reservoir was 84.6% (220 days). In non-resected patients with chemotherapy, the rate of being at home was 20.3% for 61 cases of gastric cancer patients, 30.7% for 11 cases of colon cancer, 9.6% for 14 cases of gallbladder cancer and 39.8% for 112 cases of lung cancer. The arterial infusion and embolization of hepatocellular carcinoma has made it possible to lengthen the time that patients may stay home and thereby assure good quality of life.
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PMID:[Evaluation of quality of life in arterial infusion chemotherapy of hepatocellular carcinoma]. 216 36

Forty-two patients with Stage III and IV advanced lung cancer received bronchial arterial infusion of Cyclophosphamide or Mitomycin in combination with Adriamycin and Cisplatin (CAP or MAP). Twenty-six patients were given radiotherapy too. Histologically, 16 had squamous cell carcinoma, 11 adenocarcinoma, 3 small cell anaplastic carcinoma and 1 un-classified cancer. Eleven were diagnosed by bronchial arterial radiography. The short-term results showed that complete response rate (CR) was 53.8% and partial response rate (PR) 38.5% in patients treated with combined chemotherapy and radiotherapy whereas in those treated with infusion chemotherapy, CR and PR were 0% and 81.3% respectively.
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PMID:[Bronchial arterial infusion chemotherapy with or without radiotherapy for advanced lung cancer]. 224 98

Plasma pharmacokinetics of Adriamycin (doxorubicin) has been studied after intraneoplastic administration during electrochemical treatment to patients with lung cancer that is noncurable with radiotherapy, surgery, or chemotherapy. Intraneoplastic administration of Adriamycin via the anode resulted in a dramatic change of the pharmacokinetic pattern in plasma as compared with what has been previously observed after intravenous administration. A fivefold reduction of the area under the plasma concentration time curve and a 25-fold reduction of the maximum plasma concentration was observed.
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PMID:Electrochemical treatment of cancer. III: Plasma pharmacokinetics of adriamycin after intraneoplastic administration. 231 83

A new model to predict antitumor activity of new analogues was developed, and the cross-resistance against cisplatin (CDDP) and Adriamycin (ADM) was examined. A preclinical evaluation of various new analogues using this new model was performed. The antitumor activities of KT6149, MX-2 (KRN8602), SM5887, menogaril (TUT-7), and liblomycin (NK313) were evaluated against four non-small cell lung cancer cell lines, PC-7, -9, -13, and -14; two small cell lung cancer cell lines, H69 and N231; four CDDP-resistant cell lines, PC-7/1.0, PC-9/0.5, PC-14/1.5, and H69/0.4; a human myelogenous leukemia cell line, K562; and its ADM-resistant subline, K562/ADM by clonogenic assay. The relative antitumor activities of these new analogues were compared with those of parental agents, mitomycin C, ADM, bleomycin, and several anticancer drugs, CDDP, daunomycin, vindesine, and etoposide. KT6149 was more active than mitomycin C against all lung cancer cell lines and the human myelogenous leukemia cell line. Menogaril showed greater activity than ADM, and MX-2 showed activity similar to ADM. However, the antitumor activity of SM5887 was lower than that of ADM. SM5887 and menogaril showed cross-resistance to K562/ADM. Nevertheless, the antitumor activity against K562/ADM of MX-2 was similar to that of the parental cell lines. The activity of liblomycin was similar to that of bleomycin. Thus, KT6149 appears to be the best analogue for use in a clinical trial against lung cancer. MX-2 was active even against ADM-resistant cancer cells. The values of relative resistance to CDDP or ADM were 4.7, 8.1, 7.5, 20.0, and 13.6 for PC-7/1.0, PC-9/0.5, PC-14/1.5, H69/0.4, and K562/ADM, respectively. CDDP-resistant cell lines showed no cross-resistance with other drugs in this study. K562/ADM showed cross-resistance against daunomycin, etoposide, and vindesine. In contrast, mitomycin C and bleomycin had nearly equal activity against K562 and K562/ADM. However, K562/ADM was 2.4-fold more sensitive to CDDP than its parental cell line, K562 (P less than 0.001). These results suggested that the mechanism of CDDP resistance is different from that of multidrug resistance.
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PMID:In vitro evaluation of the new anticancer agents KT6149, MX-2, SM5887, menogaril, and liblomycin using cisplatin- or adriamycin-resistant human cancer cell lines. 247 73

One hundred and one patients with oat (small) cell lung cancer have been treated with CAVE [Cytoxan, Adriamycin, Vincristine, and etoposide (VP-16)] chemotherapy +/- RA233 (a platelet-inhibiting agent). There was no difference in disease-free interval, pattern of relapse, or survival between groups.
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PMID:Chemotherapy plus RA233 in the treatment of oat cell lung cancer. 254 7

The correlation between peripheral neuropathy and cisplatin (CDDP) was elucidated in 27 patients with primary and metastatic lung cancer, who were treated with Adriamycin 30 mg/m2 day 1, CDDP 80 mg/m2 day 1, and VP-16 70 mg/m2 day 1-5 every 4 weeks. The incidence of peripheral neuropathy was 33% (9 of 27 patients) and it increased to 60% in the patients who received over 320 mg/m2 of CDDP, demonstrating a positive correlation between the incidence of this toxicity and the total dose of CDDP. However, no significant relation was observed between the grade of neuropathy and CDDP. The neuropathy was manifested in the sensory system of the distal extremities and was developed into proximal portions. The peripheral neuropathy with grade 3 was irreversible, resulting in the dose-limiting factor of this regimen.
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PMID:[Peripheral neuropathy caused by cisplatin in patients with lung cancer]. 254 51


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