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)

Chromosome 3p is frequently deleted in various cancers including examples in the lung. A novel gene, termed FHIT, was recently isolated from the fragile site at 3p14.2, with aberrant transcripts being reported in lung cancer tumor specimens. To avoid overlooking tumor-specific altered transcripts due to contaminating normal cells in primary tumors, FHIT alterations were examined in 41 lung cancer cell lines in the present study. Lack of detectable expression or exclusive expression of aberrantly spliced transcripts, often accompanied by intragenic homozygous deletions, were observed in 7 of 24 non-small cell lung cancers (29%) but in 0 of 17 small cell lung cancers (0%). Extensive reverse transcription-PCR-single-strand conformation polymorphism analysis revealed polymorphisms and alternative splicing but failed to identify point mutations. These results suggest distinct mechanisms for FHIT alterations in lung tumorigenesis and that further studies of this interesting gene are warranted.
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PMID:Molecular analysis of the FHIT gene at 3p14.2 in lung cancer cell lines. 897 Nov 57

Lobund-Wistar (L-W) rats develop adenocarcinomas spontaneously in the accessory sex glands (prostate-seminal vesicles) (P-SV) in the livers and in the lungs-all after long periods of latency. This report addresses (a) the multistage pattern of induced lung carcinomas in L-W rats and (b) the role(s) of two putative promotional agents (testosterone propionate (TP) and phenobarbital (PB) in the development of carcinomas in the lungs of L-W rats. Lung cancer is a rare slow-growing spontaneous neoplasm in L-W rats. Their incidence increased from 4.4% in avg 25.6 months (spontaneously) to 23.8% in avg 19 months following a single IV inoculation of methylnitrosourea (MNU), and further increased to 57% in avg 15 months by adding phenobarbital to the diet of MNU-inoculated rats. Three stages of lung tumorigenesis were manifested in L-W rats following treatments with MNU, or MNU + PB: hyperplasia, adenoma, and carcinoma.
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PMID:Phenobarbital promotes multistage pulmonary carcinogenesis in MNU-inoculated L-W rats. 906 74

Microsatellite instability (or replication error phenotyp) is a new molecular phenotyp of a substantial fraction of human cancers. The microsatellite instability in these cancers arises from alterations in normal regions of the genome consisting short sequences of repeated DNA. Ubiquitous changes in length of microsatellite sequences between constitutional and tumor DNA occur in about 90% of cases of HNPCC and in about 15% of cases of non-familial, sporadic colorectal cancer. Microsatellite instability is also found in a substantial percentage of sporadic endometrial, and gastric cancer, as well as in additional sporadic cancers, such as lung cancer which is usually not associated with HNPCC. Thus far, four different mismatch repair genes (hPMS1, hPMS2, hMLH1 hMSH2), all homologous to bacterial DNA repair genes have been identified as involved in HNPCC kindreds, and consequently they are associated with microsatellite instability. In conclusion, these basic genetic informations provide new insights into a new molecular pathway in oncogenesis, i.e. the occurrence of mutations in genomic stability genes leading to an increased cellular mutation rate (replication error phenotyp) and thus to cancer.
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PMID:[Microsatellite instability--a new aspects in genetics and molecular biology of hereditary nonpolyposis and sporadic colorectal tumors]. 908 61

Cytogenetic and loss of heterozygosity (LOH) studies have demonstrated that deletions of chromosome 3p occur at a high frequency in all forms of lung cancer. To clarify the role of 3p in lung tumorigenesis and to more precisely identify targets for positional cloning efforts, we have performed 3p deletion analyses (microsatellite and fluorescence in situ hybridization) in a series of lung cancer cell lines and uncultured tumor samples. Importantly, we identified homozygous deletions in four uncultured tumors and one cell line. Homozygous deletions were found in three squamous tumors within a region of 3p21 which had previously been described only in cell lines, a 1-2-megabase homozygous deletion in a small cell tumor at 3p12, and a 3p14.2 homozygous deletion in a non-small cell lung carcinoma cell line. The detection of homozygous deletions affecting these multiple regions in uncultured tumor cells substantiates the belief (previously based on deletions found only in tumor cell lines) that these sites contain important tumor suppressor genes. Along with previously reported homozygous deletions in a distal portion of 3p21.3, we now have evidence for four separate regions of 3p which undergo homozygous deletions in either uncultured lung tumors or cell lines.
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PMID:Homozygous deletions of human chromosome 3p in lung tumors. 910 23

Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the principal component in Capsicum fruits consumed worldwide as a food additive. Capsaicin is known for its hot, pungent qualities. The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is viewed as an important etiological factor in the causation of human lung cancer. In our study, a single oral dose of capsaicin administered by oral gavage at 2 mg/kg and 10 mg/kg body weight to male Syrian golden hamsters altered the in vitro metabolism of NNK by liver and lung microsomes. The most significant effect was on the inhibition of alpha-carbon hydroxylation. The orally administered capsaicin inhibited the formation of keto aldehyde (methylating pathway) and the formation of keto alcohol (pyridyloxobutylating pathway) in lung microsomes except for microsomes from animals receiving 10 mg/kg capsaicin 24 h post-treatment. In contrast, capsaicin inhibited only the methylating pathway in liver microsomal metabolism of NNK. This effect persisted at 24 h post-treatment. Since it is reported that the pyridyloxobutylating pathway enhances the effects of the more damaging methylating pathway in the metabolism of NNK (reference 25), our results suggest that any potentially chemopreventive action of orally administered capsaicin may be greater toward NNK-induced lung tumorigenesis than toward NNK-induced liver tumorigenesis.
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PMID:Effects of orally administered capsaicin, the principal component of capsicum fruits, on the in vitro metabolism of the tobacco-specific nitrosamine NNK in hamster lung and liver microsomes. 913 55

Glutathione S-transferases (GSTs) of female A/J mouse lung have been purified and characterized for their (a) structural interrelationships, (b) substrate specificities toward the ultimate carcinogenic metabolite of benzo(a)pyrene (BP), (+)-anti-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene [(+)-anti-BPDE], and (c) induction by three naturally occurring organosulfides (OSCs)-from garlic [diallyl sulfide (DAS), diallyl trisulfide (DATS) and dipropyl sulfide (DPS)], which significantly differ in their efficacy against BP-induced lung cancer in mice. The GST activity in the lung was due to two alpha class (pI 9.4 and 6.0), two mu class (pI 8.7 and 8.6), and one pi class (pI 8.9) isoenzyme. The GST isoenzyme profile of the lung was different from that of the A/J mouse forestomach, which also is a target organ for BP-induced cancer in mice. Noticeably, an alpha class heterodimeric isoenzyme (pI 9.5) present in the forestomach of A/J mouse, which is exceptionally efficient in the glutathione (GSH) conjugation of (+)-anti-BPDE [X. Hu, S.K. Srivastava, H. Xia, Y. C. Awasthi, and S. V. Singh (1996) J. Biol. Chem. 271, 32684-32688], could not be detected in the lung. The specific activities of the lung GSTs in the GSH conjugation of (+)-anti-BPDE were in the order of GST 8.9 > GST 8.7 > GST 9.4 > GST 6.0. While DPS treatment did not increase the levels of any pulmonary GST isoenzyme, the expression of pi class GST 8.9 was significantly increased in response to both DAS and DATS administrations. Interestingly, DATS, an OSC which lacks activity against BP-induced lung cancer in mice, was a relatively more potent inducer of pi class GST isoenzyme than DAS, which is a potent inhibitor of BP-induced lung tumorigenesis. The results of the present study suggest that a mechanism(s) other than GST induction is likely to be responsible for the differential effects of DAS and DATS on BP-induced lung cancer in mice. Our results also suggest that relatively lower efficacies of the OSCs against BP-induced lung cancer than against forestomach neoplasia may be attributed to (a) a lack of expression in the lung of an isoenzyme corresponding to forestomach GST 9.5 and (b) a comparatively lower level of induction of pi type GST in the lung than in the forestomach by these OSCs.
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PMID:Glutathione S-transferases of female A/J mouse lung and their induction by anticarcinogenic organosulfides from garlic. 914 32

MDM2 is an oncoprotein that inhibits p53 tumour-suppressor protein. Amplification of the MDM2 gene and overexpression of its protein have been observed in some human malignancies, and these abnormalities have a role in tumorigenesis through inactivation of p53 function. To determine the clinicopathological and prognostic value of MDM2 abnormalities in non-small-cell lung cancer (NSCLC), MDM2 gene amplification and its protein expression status were analysed in surgically resected materials. MDM2 gene amplification was detected in only 2 (7%) of the 30 tested patients. MDM2 protein was found immunohistochemically in a total of 48 (24%) of the 201 patients. MDM2 protein was slightly frequently observed in patients with adenocarcinoma, but its presence or absence was not associated with clinicopathological factors such as T-factor, N-factor, stage, tumour size, differentiation or p53 protein status. Overall, MDM2-positive patients tended to have a better prognosis (P = 0.062). In particular, among immunohistochemically p53-negative patients (n = 110), those with positive MDM2 protein expression showed significantly better prognosis (P = 0.039) and, in a multivariate analysis, MDM2 protein status was a favourable prognostic factor (P = 0.037). In contrast, among p53-positive patients (n = 91), there was no difference in prognosis depending on MDM2 protein status. Thus, in the NSCLC patients studied, MDM2 gene amplification was a minor event, but expression of its protein, which was often observed immunohistochemically, was a favourable prognostic marker, especially among patients without p53 protein accumulation. Further study is needed to determine how MDM2 protein expression results in a better prognosis.
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PMID:MDM2 gene amplification and expression in non-small-cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation. 915 50

We evaluated primary lung cancers, tumor cell lines, and preneoplastic bronchial lesions for molecular genetic abnormalities in the candidate tumor suppressor gene FHIT, which spans the FRA3B fragile site at 3p14.2. 3p14.2 allele loss was very frequent in 32 lung cancer cell lines [100% of small cell lung cancer and 88% of non-small cell lung cancer (NSCLC)] and 108 primary NSCLC cancers (45%), with numerous breakpoints indicating involvement of several distinct regions in the FRA3B site. 3p14 allele loss was least frequent in the adenocarcinoma subtype and occurred at the relatively late carcinoma in situ stage of preneoplastic bronchial lesions found in NSCLC patients. Homozygous deletions within the FHIT/FRA3B region were found in 6 of 135 (4.4%) thoracic cancer cell lines. Northern blot showed low or absent FHIT expression in most thoracic cancer cell lines tested, whereas reverse transcription-PCR showed that 59-62% exhibited aberrant FHIT transcripts but nearly always (93-100%) also expressing the wild-type transcripts. Aberrant transcripts included precise deletions of FHIT exons, insertion of non-FHIT sequences between exons and insertions replacing exons. Complete open reading frame single-strand conformational polymorphism analysis of 102 lung cancer cDNAs revealed only one nonsplicing mutation. Normal cells including bronchial epithelium, lung, and trachea expressed wild-type FHIT transcript and a variant transcript deleted for exon 8 but not the other aberrant transcripts, arguing against exon 8-deleted FHIT transcripts being tumor specific. Our findings support the conclusion that FHIT/FRA3B abnormalities are associated with lung cancer pathogenesis but that FHIT abnormalities differ from the types of mutations and lack of wild-type transcript found in classic tumor suppressor genes, and functional studies are needed to define the role of FHIT in thoracic tumorigenesis.
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PMID:FHIT and FRA3B 3p14.2 allele loss are common in lung cancer and preneoplastic bronchial lesions and are associated with cancer-related FHIT cDNA splicing aberrations. 918 30

The optimum approach to conquering cancer is prevention. Although the human diet contains components which promote cancer, it also contains components with the potential to prevent it. Recent research shows that milk fat contains a number of potential anticarcinogenic components including conjugated linoleic acid, sphingomyelin, butyric acid and ether lipids. Conjugated linoleic acid inhibited proliferation of human malignant melanoma, colorectal, breast and lung cancer cell lines. In animals, it reduced the incidence of chemically induced mouse epidermal tumors, mouse forestomach neoplasia and aberrant crypt foci in the rat colon. In a number of studies, conjugated linoleic acid, at near-physiological concentrations, inhibited mammary tumorigenesis independently of the amount and type of fat in the diet. In vitro studies showed that the milk phospholipid, sphingomyelin, through its biologically active metabolites ceramide and sphingosine, participates in three major antiproliferative pathways influencing oncogenesis, namely, inhibition of cell growth, and induction of differentiation and apoptosis. Mice fed sphingomyelin had fewer colon tumors and aberrant crypt foci than control animals. About one third of all milk triacylglycerols contain one molecule of butyric acid, a potent inhibitor of proliferation and inducer of differentiation and apoptosis in a wide range of neoplastic cell lines. Although butyrate produced by colonic fermentation is considered important for colon cancer protection, an animal study suggests dietary butyrate may inhibit mammary tumorigenesis. The dairy cow also has the ability to extract other potential anticarcinogenic agents such as beta-carotene, beta-ionone and gossypol from its feed and transfer them to milk. Animal studies comparing the tumorigenic potential of milk fat or butter with linoleic acid-rich vegetable oils or margarines are reviewed. They clearly show less tumor development with dairy products.
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PMID:Cows' milk fat components as potential anticarcinogenic agents. 918 17

Autoimmune diseases have been extensively studied in man and experimental animal models and salient points are reviewed, as a clear understanding of the immune mechanisms involved is essential if one is to understand the potential of immune interactions with established cancer cells or in the premalignant period of hyperplasia. Such reactions may be of benefit to the host, with down regulation of tumor growth, or unfavourable, with facilitation of oncogenesis and cancer growth. In particular, evidence is cited that supports a beneficial effect of the host response to non-small-cell lung cancer and the association of a poor prognosis in established breast cancer caused by a heightened immune response to the tumor. Histologic evidence supports these conclusions, as do studies of specific and nonspecific immune reactivity in breast cancer patients. The potential for cytokines to stimulate breast cancer growth, increase angiogenesis and decrease cell adhesion is reviewed, also recent evidence for autologous lymphocyte stimulation of breast cancer. Parallels between immune promotion of breast cancer in mice, caused by the mouse mammary tumor virus, and the development of breast cancer in women are also reviewed. If the mouse model has relevance for human breast cancer, one could predict that there would be a reduced incidence of breast cancer in a population of chronically immunosuppressed women following organ transplantation. Such is the case. This finding, plus the fact that all treatments that have shown efficacy in breast cancer have one thing in common, they are immunosuppressive, strongly support the role of immune facilitation of breast cancer growth and immune promotion of oncogenesis in breast cancer in a substantial number of growth.
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PMID:Evidence for immune facilitation of breast cancer growth and for the immune promotion of oncogenesis in breast cancer. 922 71


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