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)

The A-G polymorphism at codon 104 in the glutathione S-transferase P1 (GSTP1) gene was examined in 138 male lung cancer patients and 297 healthy controls. The patients had significantly higher frequency of the GG genotype (15.9%) and a lower frequency of AA (38.4%) than the controls (9.1% and 51.5%, respectively). The level of hydrophobic DNA-adducts were determined in lung tissue from 70 current smokers. Patients with the GG genotype had a significantly higher adduct level than patients with AA (15.5 +/- 10.2 vs 7.9 +/- 5.1 per 10(8) nucleotides, P = 0.006). We also analyzed the deletion polymorphism in the GSTM1 gene in 135 male patients and 342 controls. The patients were stratified according to histology, smoking dose, age, adduct level and mutational types found in the tumors (Ki-ras and p53 genes). The results consistently indicated that the GSTM1 null genotype was associated with a slightly increased lung cancer risk. When the combined GST M1 and P1 genotypes were examined, patients with the combination null and AG or GG had significantly higher adduct levels than all other genotype combinations (P = 0.011). The distribution of combined genotypes was also significantly different in cases and controls, mainly due to increased frequency of the combination GSTM1 null and GSTP1 AG or GG among patients.
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PMID:Genotypes of glutathione transferase M1 and P1 and their significance for lung DNA adduct levels and cancer risk. 923 Feb 69

We examined the expression of gelsolin in a murine ras tumor and a number of human stomach, colon, bladder, and lung cancer cell lines and tissues. In most of the cell lines and tumor tissues, gelsolin expression was undetectable or extremely low in comparison with its expression in normal epithelial cells. Upon the introduction of the exogenous human wild-type gelsolin cDNA into human cancer cell lines, the gelsolin transfectants had greatly reduced colony-forming ability and tumorigenicity in vivo. After UVC irradiation, the gelsolin-overexpressing bladder cancer cells demonstrated increased accumulation and/or protracted delay in G2 phase as compared to neotransfected cells. UVC-induced production of diacylglycerol was reduced in gelsolin-overexpressed UMUC-2 cells as compared to neo-transfected UMUC-2 cells. Levels of cyclin B in the synchronized and gelsolin-overexpressing UMUC-2 cells remained low during the G2 delay. To investigate the in vivo efficacy of gene therapy with the gelsolin tumor suppressor, we treated human urinary bladder cancers (UMUC-2 and DAB-1), inoculated in nude mice, with recombinant retrovirus packaging cells containing the human gelsolin cDNA. This gene therapy resulted in remarkable tumor growth inhibition, and prolonged survival time in the majority of animals. These observations suggest that gelsolin plays a key role as a tumor suppressor by regulating a G2 checkpoint function of cancer cells through phosphoinositol lipid metabolism, and demonstrate the potential of using the gelsolin tumor suppressor in human urinary bladder carcinoma.
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PMID:[Tumor suppressive function of gelsolin]. 930 38

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

We have developed a rapid and highly sensitive method for the detection of mutant K-ras codon 12 allele in the presence of 10(5) copies of the wild-type alleles. This sensitivity is achieved by selective amplification of mutant K-ras sequences, using a two-stage procedure with modified primers. In the first stage, primers consist of K-ras sequences in the 3' portion and polyomavirus sequence (to minimize homology with human genome) on the 5' portion. The 3' portion also consists of mismatch sequence that generates an MvaI site in normal, but not mutant, K-ras codon 12 alleles. Thus, following the first round of 20 cycles, restriction enzyme cleavage is carried out to selectively digest normal K-ras codon 12 alleles. To enrich mutant alleles, a second amplification is performed using tail primers that recognize the polyoma, but not human sequences. This design ensures that in the second amplification only mutant alleles that were pre-amplified in the first round would serve as template for this reaction. Ethidium bromide-stained polyacrylamide gel electrophoresis (PAGE) of second-stage PCR product that has been digested with MvaI is used to monitor the presence of mutant alleles, detected at sensitivity of 1/10(5). This technique offers high sensitive detection of mutant K-ras alleles using a new concept of tail-primer design and is likely to assist in identifying patients at risk to develop pancreatic, colon, or lung cancer, which harbor high incidence of mutant ras alleles.
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PMID:Quantitative enriched PCR (QEPCR), a highly sensitive method for detection of K-ras oncogene mutation. 933 87

The ras GTPase activating protein (ras GAP), a regulator of Ras activity, has two isoforms; ras GAP 120 and ras GAP 100. The latter, whose molecular size is about 100 kDa, is generated alternative splicing from the ras GAP 120 gene and is considered placenta-specific, while the former is expressed ubiquitously. As point mutations of ras are frequently observed in human tumors, we investigated the expression of ras GAP in several human cancer cell lines and samples of human colon cancer using immunoprecipitation and immunoblot analysis with an anti-GAP monoclonal antibody, B4F8, as well as reverse transcription-polymerase chain reaction (RT-PCR). ras GAP 100 protein was detected in 4 of 9 colonic, 1 of 6 gastric and 1 of 4 lung cancer cell lines as well as ras GAP 120, but not in colon cancer specimens. In contrast, ras GAP 100 mRNA was present in all tested cell lines and colon cancer specimens. Then, we investigated ras GAP 100 expression in normal tissues, ras GAP 100 protein was not detected in human normal tissues except placenta. Contrary, ras GAP 100 message was expressed in normal tissues derived from liver, stomach, colon and lymphocyte although the level of which was smaller than that in placenta. These findings demonstrate that ras GAP 100, reportedly placenta-specific, is distributed in other normal tissues at least at mRNA level and its expression is augmented in some cancer cell lines.
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PMID:Expression of the placenta-specific, 100 kDa ras GTPase activating protein in several human cancer cell lines and normal human tissues. 935 52

The mapping near Kras2 of pulmonary adenoma susceptibility 1 (Pas1), a major locus affecting inherited predisposition to lung cancer in mice prompted us to test the homologous human region (12p12) for association with lung adenocarcinoma, by a population-based study. We genotyped 213 lung adenocarcinoma patients and 219 healthy blood donor subjects for five polymorphic markers mapping in the putative region of interest. Three marker polymorphisms, located in a region spanning approximately 700 kb, were significantly associated with lung adenocarcinoma risk. Furthermore, polymorphisms in KRAS2 and PTHLH loci were also associated with tumor prognosis. These results suggest the existence of a human Pas1 homologous locus on chromosome 12p12.
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PMID:Association of chromosome 12p genetic polymorphisms with lung adenocarcinoma risk and prognosis. 936

A human lung cancer xenograft, LC-GP, producing granulocyte-colony stimulating factor and parathyroid hormone-related protein was established by transplantation into severe combined immunodeficient (SCID) mice. The lung cancer patient and SCID mice bearing LC-GP showed leukocytosis and hypercalcemia. G-CSF and PTHrP gene expression were demonstrated in the primary lung cancer, metastatic lesions and LC-GP xenograft. Immunohistochemical analysis confirmed the presence of G-CSF protein in LC-GP xenograft cells. LC-GP possessed activated c-Ki-ras oncogene (point mutation at codon 12). This LC-GP lacked apparent G-CSF receptor expression. The expression of G-CSF and PTHrP may be coregulated by the activated c-Ki-ras oncogene, and autocrine stimulation of G-CSF is unlikely.
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PMID:A human lung cancer xenograft producing granulocyte-colony stimulating factor and parathyroid hormone-related protein. 946 57

RFLP-mediated PCR has been successfully applied as a reliable tool in the detection of ras mutations in many cancers and provides a basis for "mutant-enriched PCR" protocols. We have, therefore, modified this technique to the sensitive detection of K-ras codon 12 and also p53 "hot spot" mutations, which, frequently in lung cancer, affect codons at the positions 157, 175, 245, 248, 249, and 273. With a high sensitivity of 1 mutant allele in 10(4) normal alleles, our enrichment assay allows the detection of oncogene alleles when only a few tumor cells are present within a normal cell population. Brush cytology material obtained from the tumor site of 20 patients with endoscopically apparent bronchial carcinoma was compared to macroscopically normal mucosa taken from the contralateral bronchus ("control" cytology). We found K-ras codon 12 mutations in 5 cases (25%) and p53 mutations in 13 cases (65%) in the tumor-derived cell material but, with the exception of two cases, not in cell material taken from the control cytology. Seventy-five % of the samples analyzed showed that at least one of the two oncogenes was affected. In several cases, two p53 lesions were detected concomitantly. The majority of the mutations could be reconfirmed by an alternative approach exploiting changes in the genomic RFLP pattern induced by these mutations and were also demonstrated in separate diagnostic biopsies taken. Thus, we conclude that the established enriched PCR protocol ensures a high sensitivity and preserved specificity for the diagnosis of oncogene lesions associated with lung cancer. Because conventional techniques normally yield a lower incidence of corresponding ras and p53 mutations, we think that both the high rate and the heterogeneity of p53 mutations found in some cases are, indeed, related to the increased sensitivity of this new enriched PCR technique.
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PMID:Frequent detection of ras and p53 mutations in brush cytology samples from lung cancer patients by a restriction fragment length polymorphism-based "enriched PCR" technique. 951 24

Epidemiological studies have suggested that frequent olive oil consumption may be a protective factor against lung cancer formation. Squalene, a characteristic compound in olive oil, is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and has been proposed to inhibit the farnesylation of ras oncoproteins. The present study investigated the effect of dietary olive oil and squalene in a mouse lung tumorigenesis model. Female A/J mice were fed AIN-76A diets containing 5% corn oil (control), 19.6% olive oil, or 2% squalene starting at 3 weeks before a single dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (103 mg/kg, i.p.). Animals were maintained on their respective diets throughout the study. At 16 weeks after NNK administration, 100% of the mice in the control group had lung tumors with a tumor multiplicity of 16 tumors per mouse. The olive oil and squalene diets significantly (P < 0.05) decreased the lung tumor multiplicity by 46 and 58%, respectively. The squalene diet significantly (P < 0.05) decreased lung hyperplasia by 70%. In mice fed a diet containing 2% squalene for 3 weeks, the activation of NNK was increased by 1.4- and 2.0-fold in lung and liver microsomes, respectively, but its relationship to the inhibition of carcinogenesis is not clear. These results demonstrate that dietary olive oil and squalene can effectively inhibit NNK-induced lung tumorigenesis.
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PMID:Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis by dietary olive oil and squalene. 960 Mar 60

The N',N"-bis(ethyl) polyamine analogues demonstrate great potential as chemotherapeutic agents for lung cancer. This study examines how the expression of two oncogenes frequently associated with a worsened prognosis in lung cancer, c-myc and mutated ras, as well as the phenotypic transition induced by these genes, affects the sensitivity of small cell lung cancer (SCLC) cells to these polyamine analogues. Treatment with N1,N12-bis(ethyl)spermine (BE-Spm), a representative analogue, depresses polyamine levels and is cytostatic for the NCI H209 classic SCLC cell line. Both the overexpression of c-myc and the expression of oncogenic v-Ha-ras in these cells produce phenotypes that retain sensitivity to this growth inhibition. This sensitivity to BESpm is mediated by distinct pathways in these oncogene-expressing cells. c-myc overexpression markedly increases the expression of ornithine decarboxylase, which is then down-regulated by BESpm. In contrast, v-Ha-ras expression highly induces the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase. These findings suggest that the bis(ethyl)polyamine compounds may have broad utility for the treatment of both SCLC and non-SCLC, including those expressing oncogenic c-myc and ras.
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PMID:The growth inhibitory effect of N1,N12-bis(ethyl)spermine in small cell lung cancer cells is maintained in cells expressing the c-myc and Ha-ras oncogenes. 962 77


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