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

Individual susceptibility to cancer may result from host factors including differences n metabolism, DNA repair, altered expression of protooncogenes and tumor suppressor genes, and nutritional status. Since most carcinogens require metabolic activation before binding to DNA, variations in an individual's metabolic phenotype that have detected in enzymes involved in activation and detoxification should play an essential role in the development of environmental cancer. This phenotypic metabolic variation has now been related to genetic polymorphisms, and many genes encoding carcinogen-metabolizing enzymes have been identified and cloned. Consequently, allelic variants or genetic defects that give rise to the observed variation and new polymorphisms have been recognized. Development of simple polymerase chain reaction (PCR)-based assays has enabled identification of an individual's genotype for a variety of metabolic polymorphisms. Thus, recent knowledge of the genetic basis for individual metabolic variation has opened new possibilities of studies focusing on increased individual susceptibility to environmentally induced cancer, which are reviewed with special reference to smoking-induced lung cancer. Cancer susceptibility due to chemical exposure is likely to be determined by an individual's phenotype for a number of enzymes (both activating and detoxifying) relevant to that of a single carcinogen or mixtures of carcinogens. Given the number and variability in expression of carcinogen-metabolizing enzymes and the complexity of chemical exposures, assessment of a single polymorphic enzyme (genotype) may not be sufficient. Mutations in the p53 gene are among the most common genetic changes in human cancer. The frequency and type p53 mutations can act as a fingerprint of carcinogen exposure and may therefore provide information about external etiological agents, intensity of exposure, and host factors affecting the tumorigenesis process. In human lung cancer, p53 mutations (both the mutation pattern and frequency) have been linked with tobacco smoking; the type of mutation most frequently observed is G:C to T:A transversion, a mutation preferentially induced by benzo[a]pyrene diol epoxide. An association between the presence of this transversion and the genotype deficient in glutathione S-transferase M1-mediated detoxification has been observed in lung cancer. Taken together, these findings suggest that determination of metabolic at risk genotypes in combination with levels of DNA adducts in target (surrogate) tissues and the p53 mutation pattern should allow the identification of susceptible individuals and subgroups in carcinogen-exposed populations.
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PMID:The role of individual susceptibility in cancer burden related to environmental exposure. 878 85

Retinoic acid has been shown to be an anticancer agent, and a growing literature suggests that it is the nuclear retinoic acid receptor beta2 (RARbeta2) that is primarily responsible for mediating this effect, at least in some systems. To determine whether partial inactivation of RARbeta2 would predispose to lung cancer in mice, we generated three transgenic lines expressing antisense sequences. When killed at 13-3/4-18 months of age, 21/36 animals had a total of 43 pulmonary tumors superficially visible upon necropsy, whereas among 23 nontransgenic mice, only 1 had a single visible lung tumor. A twofold higher incidence of lung tumors was seen in homozygous vs. hemizygous antisense mice. The endogenous RARbeta2 message level was reduced in transgenic lung tissue and further reduced in the tumors. RARbeta4, a truncated isoform derived from the same transcript as RARbeta2, does not carry the sequence identified by the antisense construct and its message was not as strongly affected. Immunofluorescence studies showed that RARbeta was virtually undetectable in the tumors, but present in normal tissue. We conclude that RARbeta2, but probably not RARbeta4, plays an important role in suppression of murine lung tumorigenesis.
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PMID:Lung tumors in mice expressing an antisense RARbeta2 transgene. 880 Nov 72

Pathways involved in the transduction of biological signals within cells overlap with those involved in oncogenesis. Previous studies have identified a number of discrete disturbances of some elements of these pathways in human lung cancer cells, by virtue of the overexpression or the mutation of certain key molecules. The sequence of biochemical events triggered by a mitogenic stimulus such as the exposure to bombesin-like peptides are being unravelled. The opportunity exists to identify additional changes involving regulatory proteins which may contribute to the regulation of these systems and which may function as suppressors of the malignant phenotype. Furthermore, the understanding of these pathways may identify targets for the pharmacological regulation of tumor cell response to mitogens which may be usable in the clinic.
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PMID:Involvement of signal transduction pathways in lung cancer biology. 880 5

Exposure to asbestos, particularly members of the amphibole subgroup (crocidolite, amosite), is associated with the development of malignant mesothelioma and lung cancer. Although management of asbestos in buildings and increased regulation of asbestos in workplace settings are viable approaches to the prevention of disease, the prognosis of asbestos-associated tumors is generally dismal. Moreover, although a vast amount of information is available on the responses of cells and tissues to fibers, understanding the pathogenesis of asbestos-associated malignancies is hampered by the complexity of and differences between various fiber types. Multiple interactions between components of cigarette smoke and asbestos may be important in the development of lung cancer. In this article, the general properties of asbestos fibers will be discussed with an emphasis on chemical and physical features implicated in tumorigenesis. We will then provide a brief overview of the clinical features and treatment of cancers associated with exposure to asbestos. Finally, we will review recent experimental data providing some insight into the cellular and molecular mechanisms of carcinogenesis by asbestos.
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PMID:Mechanisms of carcinogenesis and clinical features of asbestos-associated cancers. 881 62

Germline mutations of the adenomatous polyposis coli gene are associated with the dominantly inherited syndrome of familial adenomatous polyposis. Somatic mutations in this gene are an early event in sporadic colorectal tumorigenesis. Here we report a family with genetic characteristics that do not conform exactly to either of these situations. The index case and three siblings presented with colorectal cancer, and another sibling had lung cancer. There was no evidence of colorectal cancer susceptibility in previous generations, although one case of gastric cancer was observed. Using restriction fragment length polymorphism, single-strand conformational polymorphism, and sequencing analysis, we screened each living family member for alterations in the mutation cluster region of exon 15 of the APC gene. A constitutional single base pair substitution at codon 1317 was observed in two of the siblings with colorectal cancer, but neither exhibited any colonic features typical of FAP nor an early onset of cancer. This constitutional change is a missense mutation and therefore does not result in the truncation of the APC protein, the most commonly observed result of mutation in this gene. We present evidence that this change is not a polymorphism and may be capable of conferring a growth advantage. This particular germline APC mutation does not completely cosegregate with cancer in this family; therefore, we conclude that another gene locus may be responsible for the increased cancer risk observed.
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PMID:Germline APC mutation (Gln1317) in a cancer-prone family that does not result in familial adenomatous polyposis. 883 76

A remarkable volume of novel findings on the oncogenesis of cancer has been presented during the past decade, including the recognition of tumor suppressor genes, Rb and p53. In the field of molecular biology of the lung carcinogenesis, however, the study of the molecular events occurring during the progression from premalignant changes to invasive lung cancer, has been hampered by a number of difficulties. First, lung cancer includes different phenotypes: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), which contains three different main types: adenocarcinoma, squamous cell carcinoma and large cell carcinoma. The development of these phenotypes of lung cancer may involve different molecular mechanisms. Second, the specific familial genetic changes of lung cancer are largely unknown. Third, the early detection of lung cancer is difficult. In this article, we review recent topics in the field of molecular oncology of the lung. We will also refer to our novel detection systems for mutations in the cells in the tissue specimens. While specific oncogenesis of lung cancer phenotypes might eventually become evident, and successful gene-therapy might be carried out according to newly established molecular technology in the near future, we should attempt to evaluate the independent multi-steps of oncogenesis in each lung cancer patient.
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PMID:[Prospective views for molecular oncology of the lung]. 883 72

Genomic imprinting is defined as a gamete-specific modification causing differential expression of the two alleles of a gene in somatic cells. While insulin-like growth factor 2 (IGF2) and H19 both at 11p15 are imprinted in normal lung, we observed frequent loss of imprinting (LOI) of the IGF2 and H19 genes in the lung cancer. While genomic imprinting is thought to play an important role in embryonal development and possibly in the development of certain embryonal tumors such as Wilms' tumor, these results suggest that altered imprinting may also play a role in the oncogenesis of this common cancer of adults, lung cancer.
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PMID:[Altered genomic imprinting in the IGF2 and H19 genes in human lung cancer]. 883 3

Administration of the heme precursor 5-aminolevulinic acid (ALA) leads to the selective accumulation of the photosensitizer protoporphyrin IX (PpIX) in certain types of normal and abnormal tissues. This phenomenon has been exploited clinically for detection and treatment of a variety of malignant and nonmalignant lesions. The present preclinical study examined the specificity of ALA-induced porphyrin fluorescence in chemically induced murine lung tumors in vivo. During the early stages of tumorigenesis, ALA-induced PpIX fluorescence developed in hyperplastic tissues in the lung and later in early lung tumor foci. In early tumor foci, maximum PpIX fluorescence occurred 2 h after the administration of ALA and returned to background levels after 4 h. There was approximately a 20-fold difference in PpIX fluorescence intensity between tumor foci and the adjacent normal tissue. The specificity of ALA-induced fluorescence for hyperplastic tissues and benign tumors in lung during tumorigenesis suggests a possible use for this fluorochrome in the detection of premalignant alterations in the lung by fluorescence endoscopy. Two non-small cell lung cancer cell lines developed ALA-induced PpIX fluorescence in vitro. These lines exhibited a light-dose-dependent phototoxic response to ALA photodynamic therapy (PDT) in vitro. Because PpIX is a clinically effective photosensitizer for a wide variety of malignancies, these results support the possible use of ALA-induced PpIX PDT for lung cancer.
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PMID:Detection of early stages of carcinogenesis in adenomas of murine lung by 5-aminolevulinic acid-induced protoporphyrin IX fluorescence. 886 73

Naturally occurring and synthetic isothiocyanates are among the most effective chemopreventive agents known. A wide variety of isothiocyanates prevent cancer of various tissues including the rat lung, mammary gland, esophagus, liver, small intestine, colon, and bladder. Mechanistic studies have shown that the chemopreventive activity of isothiocyanates is due to favorable modification of Phase I and Phase II carcinogen metabolism, resulting in increased carcinogen excretion or detoxification and decreased carcinogen DNA interactions. In the majority of studies reported, the isothiocyanate must be present at the time of carcinogen exposure in order to observe inhibition of tumorigenesis. Our studies have focused on the naturally occurring isothiocyanates phenethyl isothiocyanate (PEITC) and benzyl isothiocyanate (BITC) as inhibitors of lung cancer. The carcinogens employed in these studies have been the major lung carcinogens in tobacco smoke- 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (BaP). Combinations of chemopreventive agents that inhibit tumorigenesis by NNK and BaP in rodents may be effective in addicted smokers. PEITC is an effective inhibitor of lung tumor induction by NNK in F-344 rats and A/J mice. BITC but not PEITC inhibits BaP induced lung tumorigenesis in A/J mice. PEITC is a selective inhibitor of the metabolic activation of NNK in the rodent lung, and studies in smokers who consumed watercress, a source of PEITC, indicate that the metabolic activation of NNK is also inhibited by PEITC in humans. Combinations of chemopreventive agents active against different carcinogens in tobacco smoke may be useful in the chemoprevention of lung cancer.
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PMID:Chemoprevention of lung cancer by isothiocyanates. 888 22

Immunohistochemical analysis of Bcl-2 oncoprotein, one of the oncogenes associated with the regulation of programmed cell death, was performed on 12 surgically resected tumors of the combined type of small-cell lung cancer. Ten cases (83%) expressed Bcl-2 oncoprotein within the tumor tissues. Two of them showed its expression in both the small cell carcinoma and non-small cell carcinoma types, and 7 cases exhibited Bcl-2 expression only in the portion of the small cell carcinoma. Considering previous reports indicating a high prevalence of Bcl-2 oncoprotein expression in small cell lung cancer, it is suggested that Bcl-2 oncoprotein even in the combined type of lung cancer may play an important role in tumorigenesis and tumor development and ensuing histological alterations between small cell carcinoma and non-small cell carcinoma types.
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PMID:Bcl-2 oncoprotein expression is increased especially in the portion of small cell carcinoma within the combined type of small cell lung cancer. 893 49


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