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

Small cell lung cancer (SCLC) tumors frequently display deletions on the short arm of chromosome 3 suggesting the existence of a 'tumor suppressor' gene within that region whose functional inactivation may be involved in tumorigenesis. Recently, a hybrid, HA(3)BB9F, was identified that contains a small fragment of human chromosome 3 of approximately 2 Mb on a mouse (A9) background (Killary et. al., 1992). This hybrid was utilized to define a functional tumor suppressor gene within 3p22-p21 which could suppress the tumorigenic properties of the mouse fibrosarcoma cell line. The existence of a tumor suppressor gene in the region 3p22-p21 is supported by the present report which describes the assessment of 89 SCLC and 32 non-SCLC lung cancer tumors and cell lines for the existence of a homozygous deletion(s) at 43 loci on the short arm of chromosome 3. One of the SCLC cell lines was found to harbor a homozygous deletion involving the loss of five markers on chromosome 3p. All five of the markers map to the region 3p21.3-p21.2 and four of the five markers are located within the chromosome 3 fragment exhibiting properties of tumor suppression in the HA(3)BB9F hybrid. The other tumors analysed all retained at least one copy of each of the markers assessed.
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PMID:A homozygous deletion on chromosome 3 in a small cell lung cancer cell line correlates with a region of tumor suppressor activity. 839 35

A retroviral vector system was developed to transduce a K-ras antisense construct efficiently into human cancer cells. A 2-kb fragment of K-ras gene DNA in antisense orientation was linked to a beta-actin promoter and inserted into retroviral vector LNSX in two different orientations. The constructs were transfected into amphotropic packaging cell line GP+envAm12 followed by alternating transduction between the ecotropic packaging cell line psi-2 and GP+envAm12. Titers up to 9.7 x 10(7) colony-forming units (cfu)/ml were achieved without detectable replication-competent virus. The human large cell lung carcinoma cell line H460a, which has a homozygous codon 61 K-ras mutation, was transduced with an efficiency of 95% after five to seven repeated transductions. DNA polymerase chain reaction (PCR) and genomic DNA Southern blot analysis showed that the retroviral construct was integrated into the genome of H460a cells. K-ras antisense RNA expression was detected in the cells by Northern analysis, slot blot hybridization, and reverse transcriptase-PCR. Translation of the mutated K-ras p21 protein RNA was specifically inhibited, whereas expression of other p21 species was unchanged. Proliferation of H460a cells was suppressed 10-fold following transduction by the antisense construct. Colony formation in soft agarose and tumorigenicity in an orthotopic lung cancer model in nu/nu mice were dramatically reduced in H460a cells expressing antisense K-ras. We conclude that an antisense construct for K-ras can be expressed effectively in a retroviral vector that can efficiently transduce human cancer cells.
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PMID:Retroviral vector-mediated transduction of K-ras antisense RNA into human lung cancer cells inhibits expression of the malignant phenotype. 839 92

Genomic imprinting at 11p15 is suggested to play a role in certain pediatric tumors such as Wilms' tumor, based on the findings of selective maternal loss of this chromosomal region. Although the allele loss at 11p15 is also frequent in a number of cancers of adults including lung, breast, and bladder cancers, possible involvement of genomic imprinting in these tumors has not been investigated extensively. p57KIP2, a newly described member of the p21 cyclin-dependent kinase (CDK) inhibitor family which is thought to negatively regulate the cell cycle at the G1 checkpoint, has been mapped to 11p15. In the present study, we searched for somatic p57KIP2 mutations in lung cancer, but failed to find such alterations. Interestingly, however, we found that the p57KIP2 gene is imprinted with maternal expression and that the maternal alleles had been selectively lost in 11 of 13 (85%) lung cancer cases carrying 11p15 deletions, this being a significant bias (p=0.01). These data provide the first evidence that genomic imprinting may play a role in the oncogenesis of not only rare pediatric tumors but also this common cancer of adults, suggesting that the imprinted p57KIP2 CDK inhibitor gene is a potential target for maternally biased 11p15 deletions.
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PMID:Selective maternal-allele loss in human lung cancers of the maternally expressed p57KIP2 gene at 11p15.5. 864 40

We have determined the allelotypes of 215 established lung cancer cell lines by PCR analysis at six loci on the short arm of chromosome 3 (3p): D3S3 (3p12-p13), D3S30 (3p13), D3S2 (3p14-p21.1), D3S32 (3p21), D3F15S2 (3p21), and THRB (3p24). Eighty-seven small cell lung cancer (SCLC), 93 non-small cell lung cancer (NSCLC), 6 extrapulmonary SCLC, 6 mesothelioma, and 23 normal B lymphocyte (BL) cell lines were analyzed. Low levels of heterozygosity at all six 3p loci were seen in both the SCLC and NSCLC cells. SCLC cell lines exhibited the lowest frequencies of heterozygosity at D3S3 (3%), D3S2 (3%), D3F15S2 (10%), and THRB (6%) when compared with frequencies of 8, 42, 48, and 34% at these same loci in the normal population. The lowest frequencies of heterozygosities among the NSCLC cell lines were seen at D3S3 (5%), DF15S2 (17%), and THRB (15%). Adenocarcinoma (Ad) was the only subtype of NSCLC that exhibited any heterozygosity (7%) at D3S3. In addition to D3S3, the lowest frequencies of heterozygosity were seen at D3F15S2 for Ad (9%), D3S2 for large cell carcinomas (8%), and THRB for adenosquamous (0%), bronchioloalveolar (0%), and large cell (8%) carcinomas. In summary, the 3p chromosome region near the D3S3 locus (3p12-p13) appears to be involved in all forms of lung cancer with additional involvement of regions close to the D3S2 (3p14-p21.1), D3F15S2 (3p21), and THRB (3p24) loci.
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PMID:Frequent involvement of chromosome 3p alterations in lung carcinogenesis: allelotypes of 215 established cell lines at six chromosome 3p loci. 880 2

In previous investigations p53 polymorphisms and haplotypes have been found to be associated with different types of cancer. In this paper the codon 31 polymorphism of the p53-inducible protein p21 was studied in 144 Swedish lung cancer patients and two different control groups: 95 patients with chronic obstructive pulmonary disease (COPD) and 761 healthy controls. An increased frequency of the p21 codon 31 A1 (arg) allele was found in lung cancer patients, especially in comparison with COPD patients (p = 0.004). There was a significantly increased frequency among lung cancer patients of individuals carrying the arg allele both in comparison with COPD controls (OR = 5.2, 95% CI 1.5-18.1) and healthy controls (OR = 1.7, 95% CI = 1.0-2.9). The results of this and previous studies indicate that allelic variants of both p53 and its effector protein p21 may have an influence on lung cancer.
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PMID:Association between the p21 codon 31 A1 (arg) allele and lung cancer. 880 25

The pathogenesis of mesenchymal and epithelial lung reactions was studied after a single intratracheal instillation of quartz into rats. Relationships between transforming growth factor beta1 (TGF-beta1) and the ras and p53 genes were investigated in silicosis and associated lung cancer. Immunohistochemical reactivity to mature TGF-beta1 was localized intracellularly in fibroblasts and macrophages at the periphery of silicotic granulomas and in stroma adjacent to hyperplastic alveolar type II cells and extracellularly in connective tissue matrix adjacent to hyperplastic alveolar type II cells. TGF-beta1 precursor was localized intracellularly in hyperplastic alveolar type II cells adjacent to granulomas and in the cells of adenomas, but not in carcinomas. Hematite-treated controls showed no reactivity to TGF-beta1. Immunohistochemical localization of pan-reactive p21 ras protein in quartz-treated rat lungs was increased in hyperplastic alveolar type II cells adjacent to granulomas, but not in adenomas and carcinomas. Foci of nuclear immunoreactivity to p53 protein were observed in 25% of the carcinomas.
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PMID:Transforming growth factor beta1, ras and p53 in silica-induced fibrogenesis and carcinogenesis. 892 85

Recent advance in cell-molecular biological studies have revealed various prognostic factors in lung cancer. The aim of this paper is to critically review the current status of molecular biological prognostic markers in non-small cell lung cancer. DNA ploidy, AgNORs and PCNA as marker of tumor cellular proliferative activity are reported to be a prognostic marker but still remain controversial. The proteases such as uPA, MMPs and CB catalyze degradation of the extracellular matrix and basement membranes. Although the prognostic implications of the uPA and MMPs still remain unclear, cathepsin B appears to be one of the most useful prognostic markers so far reported for non-small cell lung cancer. In a number of studies, genetic abnormalitis has been reported to be a prognostic marker in cancer patients. In non-small cell lung cancer, the prognostic implication of the altered p53 expression or ras p21 expression still remain unclear, especially p53 is conflicting. The most useful clinical prognostic marker may be obtained by the combined analysis of some prognostic information.
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PMID:[Molecular biological prognostic markers in lung cancer]. 904 11

The purpose of the present communication was to determine in lung cancer patients and healthy donors if there was a possible association between cancer and biomarkers of cytogenetic damage and ras p21 oncoprotein levels, and if various exogenous confounding factors (such as smoking habit) and endogenous ones (age, sex, etc.) could affect these biomarkers. Peripheral blood and plasma were collected from 31 lung cancer patients prior to treatment and 35 healthy donors of a similar socioeconomic status and from the same region in Poland. Chromosomal aberrations (CA), sister chromatid exchanges (SCE), high frequency cells (HFC), and proliferative rate index (PRI) were examined from the blood and ras p21 oncoproteins from the plasma. These parameters were used as biomarkers of genotoxic anomalies. All the biomarkers were examined for their relationship to confounding factors of age, sex, smoking habit, and immediate family cancer history. Results were analyzed by a t-test, analysis of variance (ANOVA), and stepwise multivariate regression analysis. All types of CA (including and excluding gaps), percent aberrant cells, SCE, and ras p21 oncoproteins were statistically significantly higher in cancer patients than in the healthy donors. Although there were smaller numbers of females in the cancer patients group who were older than the males, there was a difference due to sex (gender) with statistically significant increases in females for CA, SCE, and HFC, but there was no increase for ras p21 oncoproteins. Cytogenetic damage was not related to other cancers in the immediate families of the groups. All major CA parameters differed significantly between smokers and non-smokers in the cancer patients group, and SCE and HFC differed in the healthy donors group. Such parameters also showed a significant variability with the number of cigarettes smoked and the years of smoking habit. Multivariate regression analyses showed a significant association between cytogenetic damage, ras p21 oncoproteins, and cancer. In conclusion, cytogenetic damage and ras p21 oncoproteins in this study appear to be biomarkers associated with cancer, but have not been proved causally, and confounding factors such as age, sex (gender), and smoking can have an impact on them.
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PMID:Factors affecting various biomarkers in untreated lung cancer patients and healthy donors. 932 45

A large-scale sequencing analysis of genomic DNA in the vicinity of homozygous deletion on chromosome 3p found in a lung cancer cell line disclosed that the gene encoding phospholipase C delta 1 (PLCD1) is located just distal to the region removed by the deletion We report the genomic structure of this gene, which consists of 15 exons and spans about 22 kb, and its precise localization to chromosome 3p22-->p21.3.
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PMID:Genomic structure of the human PLCD1 (phospholipase C delta 1) locus on 3p22-->p21.3. 934 9

6-[3-(1-Adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN or CD437), originally identified as a retinoic acid receptor gamma-selective retinoid, was previously shown to induce growth inhibition and apoptosis in human breast cancer cells. In this study, we investigated the role of AHPN/CD437 and its mechanism of action in human lung cancer cell lines. Our results demonstrated that AHPN/CD437 effectively inhibited lung cancer cell growth by inducing G0/G1 arrest and apoptosis, a process that is accompanied by rapid induction of c-Jun, nur77, and p21(WAF1/CIP1). In addition, we found that expression of p53 and Bcl-2 was differentially regulated by AHPN/CD437 in different lung cancer cell lines and may play a role in regulating AHPN/CD437-induced apoptotic process. On constitutive expression of the c-JunAla(63,73) protein, a dominant-negative inhibitor of c-Jun, in A549 cells, nur77 expression and apoptosis induction by AHPN/CD437 were impaired, whereas p21(WAF1/CIP1) induction and G0/G1 arrest were not affected. Furthermore, overexpression of antisense nur77 RNA in A549 and H460 lung cancer cell lines largely inhibited AHPN/CD437-induced apoptosis. Thus, expression of c-Jun and nur77 plays a critical role in AHPN/CD437-induced apoptosis. Together, our results reveal a novel pathway for retinoid-induced apoptosis and suggest that AHPN/CD437 or analogs may have a better therapeutic efficacy against lung cancer.
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PMID:Molecular determinants of AHPN (CD437)-induced growth arrest and apoptosis in human lung cancer cell lines. 967 82


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