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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of vitamin A on the development of chemically induced lung carcinomas in rats was investigated. Rats were maintained on low, "normal" and excess levels of retinyl acetate (RA). Respiratory tract-squamous carcinomas were induced by intratracheal injections of 3-methylcholanthrene (3-MCA). The carcinogen doses used ranged from 1.25 to 10.0 mg of 3-MCA. Serial sacrifices conducted during the first 20 weeks following carcinogen exposure showed that metaplastic lung nodules, presumed to be precursors of later appearing carcinomas, occurred earlier and at higher incidence in rats maintained on low levels of RA than in rats maintained on moderate or high levels of RA. The development of invasive pulmonary carcinomas was enhanced at all four carcinogen doses in rats receiving low levels of RA as compared to rats receiving moderate or high levels of RA. No consistent difference in lung cancer incidence existed between the groups receiving normal and high levels of RA. The data clearly show an increased susceptibility of vitamin A-deficient rats to develop chemically induced lung cancers. Possible mechanisms underlying this effect are discussed.
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PMID:Vitamin A and the susceptibility of respiratory tract tissues to carcinogenic insult. 51 Feb 47

The studies reported here demonstrate some of the factors affecting the binding of benzo(a)pyrene (BP) to macromolecules in cultured human bronchial mucosa. Bronchial specimens were obtained at either surgy or "immediate" autopsy from patients with and without lung cancer. Grossly normal-appearing pieces of bronchus were cultured in a chemically defined medium, i.e., CMRL 1066 medium containing 1 mug insulin per ml, 0.1 mug beta-retinyl acetate per ml,, 0.1 mug hydrocortisone hemisuccinate per ml, 2 mM L-glutamine, 100 units penicillin G per ml, and 100 mug streptomycin per ml. After 7 days, explant cultures were exposed to [3H]BP, usually for 24 hr, and then binding to total cellular macromolecules was studied by autoradiography, and binding to DNA was measured following isolation of DNA from bronchial mucosal cells. The extent of binding of [3H]BP was dependent on dose of BP, length of exposure to [3H]BP, and temperature. By autoradiography, bronchial epithelial cells bound more [3H]BP than stromal fibroblasts. Both 7,8-benzoflavone and butylated hydroxytoluene appeared to reduce the level of [3H]BP bound to DNA, while nicotine apparently did not alter the level of binding. These studies demonstrate that the bronchial mucosa, an important human cancer target tissue, has the capability to form metabolites of BP which bind to macromolecules including DNA. In addition, 7,8-benzoflavone and butylated hydroxytoluene, both known to alter the microsomal metabolism of BP, reduce the level of [3H]BP bound to DNA.
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PMID:Binding of (3H)benzo(a)pyrene to DNA in cultured human bronchus. 2809 25

The capacity of alveolar macrophages and peripheral blood monocytes from patients with non-small cell lung cancer to develop tumoricidal function after in vitro stimulation with different macrophage activators was investigated. Alveolar macrophages were found to be impaired in their ability to develop cytotoxic activity compared with either the peripheral blood monocytes from the same patients or alveolar macrophages from patients with nonmalignant lung disorders. This result was observed consistently under diverse culture conditions and with different macrophage activators including gamma-interferon (gamma-IFN), granulocyte-macrophage colony-stimulating factor (GM-CSF), phorbol myristate acetate, or endotoxin. The impairment in tumoricidal function observed in alveolar macrophages was not associated with reduced target cell binding compared to peripheral blood monocytes. Alveolar macrophages from patients with lung cancer were found to secrete significantly greater amounts of tumor necrosis factor (TNF) and interleukin-1 (IL-1) than either peripheral blood monocytes from the same patients or alveolar macrophages from the patients with nonmalignant disorders. These results are consistent with either different regulatory pathways for cytotoxicity and cytokine secretion in the alveolar macrophages of patients with lung cancer or diversity in the subpopulations of cells responsible for these functions.
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PMID:Impaired tumoricidal function of alveolar macrophages from patients with non-small cell lung cancer. 165 12

Human aortic endothelial cells, isolated at autopsy from a 52-year-old male dying from lung cancer, were treated with simian virus 40 (SV40). One colony was isolated from the infected endothelial cell culture 4 weeks after infection. The cells expressed SV40 large T antigen and p53 protein (p53) in their nuclei but lacted the characteristics of a transformed phenotype. The cells grew well in a monolayer over the 97th passage and exhibited Factor VIII-related antigen, Ulex europaeus 1 agglutinin (UEA-1) as endothelial cell markers, and a well-developed fibronectin network. The amount of prostacyclin synthesized by the cells was less than the amount synthesized by normal aortic or umbilical cord vein endothelial cells. The cells produced relatively large amounts of procollagenase, and 12-o-tetradecanoyl-phorbol-13-acetate (TPA) augmented the ability of the cells to produce this enzyme. These immortalized human aortic endothelial cells, which have some characteristics of normal endothelial cells and, like capillary endothelial cells, have the ability to produce collagenase, will probably prove useful for studies of atherosclerosis and angiogenesis.
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PMID:Collagenase production by immortalized human aortic endothelial cells infected with simian virus 40. 167 13

Hematopoietic growth factors are produced by a number of human tumors. We extracted RNA from selected human tumor cells known to produce at least one hematopoietic growth factor and found high levels of abnormally stable cytokine messenger (m)RNA. Half-life experiments performed after preventing RNA synthesis by exposing cells to actinomycin D before RNA extraction showed stabilization of cytokine messages in tumor cells in liquid culture as well as in human tumor xenografts grown in mice. Exposure to the phorbol ester phorbol 12-myristate 13-acetate (TPA) caused enhancement of granulocyte-macrophage colony-stimulating factor (GM-CSF) message level in lung cancer cells and in control fibroblasts but elevated levels persisted far longer in the tumor cells. In normal cells, an AU-rich sequence in the 3' untranslated region of cytokine mRNAs confers lability to the message. Although a beta-globin gene expression vector containing this region appears to produce unstable mRNA in lung cancer cells, cytokine mRNAs, which also contain this sequence, are very stable in the tumors we studied. This may indicate that another region of the cytokine mRNA molecule is of greater importance than the AU-rich region in determining mRNA stability in tumor cells.
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PMID:Cytokine messenger RNA stability is enhanced in tumor cells. 184 61

The scintigraphic "flare" phenomenon on bone imaging refers to an increase in intensity of tracer uptake in sites of bone metastases and/or the appearance of "new" lesions, which occur shortly after commencement of hormonal therapy or chemotherapy for breast, prostate, or lung cancer. In this study, we observed that scintigraphic flare can occur in patients with prostate cancer following treatment with the "hormone-like" luteinizing hormone releasing hormone analog, leuprolide acetate. Twenty-six patients with prostate cancer being treated with leuprolide acetate underwent serial bone scans at three-month intervals. Five (19.2%) of the 26 patients had findings consistent with a scintigraphic flare on bone scans obtained between three and six months after initiation of therapy. These scan findings should not be confused with progression of skeletal metastases.
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PMID:Leuprolide therapy for prostate cancer. An association with scintigraphic "flare" on bone scan. 211 49

A 70-year-old man having severe ischemic heart diseases developed bilateral, duplicate lung cancer of large cell and squamous cell types. Chemoimmunotherapy consisting of carmofur, picibanil inhalation, i.m. sizofilan, and peroral bestatin was started, and 3 months later, peroral medroxyprogesterone acetate was added. The tumor regressed, and the patient survived more than 34 months. This type of nonaggressive regimen may thus be useful for tumors other than adenocarcinomas, too.
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PMID:Medroxyprogesterone acetate for lung cancer. 214 30

Eighty-nine patients over 70 years old with untreated lung cancer, of various cell type and in various stages, were randomly assigned to chemotherapy (CT) alone or CT combined with medroxyprogesterone acetate (MPA). CT consisted of cisplatin, 60 mg/m2 i.v., along with etoposide (VP-16), 150 mg/m2 i.v., on day 1. The VP-16 was increased to 200 mg/m2, orally, on day 3. The entire regimen was given every 4 weeks for a maximum of six cycles. MPA was administered in daily 500-mg doses, i.m., 5 days a week for 1 month, followed by 1000 mg i.m., once a week, for 5 months. Changes in body weight and appetite were documented. After two cycles of CT, 64 patients were found to be evaluable for response. Forty-five had non-small-cell lung cancer (NSCLC) and 19 had small-cell lung cancer (SCLC). Thirty-seven patients had received CT alone and 27 CT plus MPA. In NSCLC, the objective response to CT alone was 36% versus 37% with CT plus MPA. In SCLC, the corresponding figures were 63% and 22%. The overall objective response rate was 60% in NSCLC and 48% in SCLC. Median survival using CT alone was 10 months for NSCLC patients and 11 months for SCLC patients. Using CT plus MPA, it was 10 months for NSCLC patients and 7 months for SCLC patients. In the control arm, 1-year survival was 42% for NSCLC patients and 48% for SCLC patients; in those who were given MPA, it was 48% for NSCLC patients and 9% for SCLC patients. Improved appetite and weight gain were reported more frequently by MPA patients, and they did not complain of CT's usual side effects. The fact that MPA had no significant effect on CT response or survival in patients also treated with a combination of cisplatin and VP-16, along with the small survival advantage for the control group in SCLC patients, suggests that combining MPA and CT may result in improved quality of life.
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PMID:The clinical effect of medroxyprogesterone (MPA) in elderly patients with lung cancer. 215 16

The growth inhibitory effect of tumour promoters on human leukaemia and lung cancer cell lines was examined using the [3-(4,5 dimethylthiazol)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. The four cell lines used were the K562 human leukaemia cell line, its adriamycin (ADM)-resistant subline (K562/ADM), which shows the mdr phenotype, PC-9 (a human lung adenocarcinoma cell line) and its cisplatin (CDDP)-resistant subline (PC-9/CDDP), which does not show the mdr phenotype. Phorbol 12-tetradecanoate-13-acetate (TPA) and the TPA-type tumour promoters, aplysiatoxin and debromoaplysiatoxin, inhibited the growth of the two parental cell lines, K562 and PC-9. The non-TPA-type tumour promoter, okadaic acid, also inhibited the growth of the two parental cell lines in a dose-dependent manner. TPA-type and okadaic acid inhibited the growth of K562/ADM more weakly than that of K562, and showed no growth inhibition in PC-9/CDDP. Anhydrodebromoaplysiatoxin, an inactive derivative of the TPA-type tumour promoter, could suppress the growth of K562 and K562/ADM only at high concentration (more than 50 pM) and it showed similar growth inhibitory effects on the two cell lines. Okadaic acid tetramethyl ether, the inactive form of the non-TPA-type tumour promoter did not inhibit the growth of any of the cell lines. The growth inhibitory effect of these compounds was well correlated with their tumour-promoting activity. A study of the accumulation of okadaic acid revealed that the amount of 3H-okadaic acid in K562/ADM and PC-9/CDDP was similar to that in their parental cells indicating that cross-resistance to this tumour promoter in the drug-resistant cell lines is not due to a difference in the amount of drug accumulated in sensitive and resistant cells. These results suggest the presence of another common mechanism for resistance to ADM and CDDP as well as to TPA- or non-TPA-type tumour promoters.
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PMID:Cross-resistance to tumour promoters in human cancer cell lines resistant to adriamycin or cisplatin. 220 49

A search of the literature using National Library of Medicine databases and individual cancer journal articles yielded over 500 compounds with published chemopreventive activity in animals. From these, an initial 16 agents or agent combinations have been evaluated in the following animal tumor models: mouse skin papillomas/carcinomas induced by 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate; rat breast adenocarcinoma induced by N-methyl-N-nitrosourea or 7,12-dimethylbenz(a)anthracene; hamster lung carcinoma induced by N-methyl-N-nitrosourea or diethylnitrosamine; mouse bladder papillary carcinoma induced by N-butyl-N-(4-hydroxybutyl)nitrosamine; and rat and mouse colon cancer induced by azoxymethane/methylazoxymethanol acetate. Some of the most interesting positive results observed include 4-hydroxyphenyl retinamide plus tamoxifen in breast cancer, piroxicam in colon cancer, dimethylfluoroornithine in breast and bladder cancer, oltipraz in lung cancer, dehydroepiandrosterone in colon cancer, and molybdate in bladder cancer. Eighteen human intervention trials in progress are described that involve the following agents: beta-carotene (eight trials). Retinol/retinoic acid (seven trials), vitamins C and E (three trials), 4-hydroxyphenyl retinamide (one trial), piroxicam (one trial), and calcium (one trial). By organ site these studies involve cancer of the lung (six studies), skin (five studies), colon (four studies), breast (one study), and uterine cervix (two studies).
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PMID:Identification of candidate cancer chemopreventive agents and their evaluation in animal models and human clinical trials: a review. 240 15


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