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

We previously reported a high incidence of loss of heterozygosity (LOH) on chromosome 2q33 in neuroblastoma (NB), observed in various types of human cancers including lung cancer, head and neck cancer and follicular thyroid carcinoma. To better elucidate the role of chromosome 2q aberrations in NB, we examined common allelic imbalance (AI) regions on chromosome 2q in 82 NB patients using 10 polymorphic microsatellite markers. AI on 2q was detected in 26 (32%) of 82 NB cases. There was a distinct common AI region between the D2S115 and D2S307 markers on 2q33. The distance between these markers was about 2.0 cM. Recently, the caspase 8 and caspase 10 genes, both of which encode cystein protease, were mapped to chromosome 2q33. Since the common AI region on 2q33 includes the caspase 8 and caspase 10 genes, the alterations of these genes were examined further. Absent or reduced expression of caspase 8 and caspase 10 were found in 19 (70%) of 27 and two (7%) of 27 NB cell lines by reverse transcription-polymerase chain reaction, respectively. A missense mutation was detected at codon 96, GCT (Alanine) to GTT (Valine), of the caspase 8 gene in one of the NB cell lines lacking caspase 8 expression. Thirteen (68%) of 19 cell lines lacking caspase 8 expression displayed methylation of the CpG island of the caspase 8 gene, whereas only one (13%) of eight cell lines with caspase 8 expression showed caspase 8 methylation (P=0.031). Furthermore, there was a significant association between AI at 2q33 and loss of caspase 8 expression (P=0.026). These results indicated that there was a tumor suppressor gene in the common AI region on chromosome 2q33 involved in the pathogenesis of a subset of NB. It is possible that the caspase 8 gene is one of the candidate tumor suppressor genes for NB and inactivation of this gene plays an important role in the tumorigenesis of NB through mainly its methylation.
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PMID:Allelic imbalance on chromosome 2q and alterations of the caspase 8 gene in neuroblastoma. 1146 26

The CYFRA 21-1 assay which detects the cytokeratin 19 (CK19) fragment is widely used as a tumor marker for lung cancer. We previously suggested that the failure of PCR amplification of exon 1 is closely related to the inability of the expression of mRNA for CK19, and hypothesized that point mutations might exist within exon 1. In order to prove this, sequence analysis of the promoter region and exon 1 was performed in 14 human lung cancer cell lines. Among the 14 lung cancer cell lines evaluated, point mutations within the promoter region (at -99, G-->C) of the CK19 gene were demonstrated in two cell lines (Lu135 and HI1017). In addition, point mutations within exon 1 (at 90, T-->C, Ala-->Ala and at 179, G-->C, Gly-->Ala) were also demonstrated in three cell lines (LU135, HI1017, and LC2/AD). Point mutations within the promoter region of CK19 (at -99) and within exon 1 (at 179) were confirmed by analysis of digestion by specific restriction enzymes. Since the same point mutation within exon 1 (at 179) was observed in genomes of normal volunteers, this mutation was considered as a single nucleotide polymorphism. In contrast, there were no mutations within the promoter region of exon 1 in genomes of normal volunteers. After a computer search, it was demonstrated that several transcription factors bind to the sense primer sequence which was designed for amplification of exon 1. In addition, after point mutations within the promoter region occurred (at -99), new sequences appeared to which known transcription factors (AP2) bind. In conclusion, analysis of genomic DNA for CK19 suggested that expression of mRNA for CK19 was regulated by several transcription factors which bound to the specific sequence with the promoter region of the CK19 gene. It was also suggested that the mutation in the promoter region of the CK19 gene down-regulated the expression of mRNA for CK19.
Lung Cancer 2001 Dec
PMID:The point mutation in the promoter region and the single nucleotide polymorphism in exon 1 of the cytokeratin 19 gene in human lung cancer cell lines. 1171 36

We have recently shown that lysine mutations in p53's putative C-terminal acetylation sites result in increased stability and cytoplasmic distribution of the p53 protein in a human lung cancer cell line. In the present study, we showed that when lysine residues 372, 373, 381, and 382 of p53 were substituted with alanine, the resulting A4 protein was resistant to MDM2-mediated proteosomal degradation but was highly sensitive to human papillomavirus E6-mediated proteolysis. When A4 and wild-type p53 were transfected into MDM2-overexpressing MCF-7 cells, A4 significantly reduced colony formation in vitro, when compared with wild-type p53. Our results suggest that A4 exerts a growth-inhibitory effect more efficiently than wild-type p53 does in cell lines that overexpress MDM2 and may therefore be a better therapeutic tool than wild-type p53 for certain cancers in which MDM2 is amplified or overexpressed.
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PMID:Multiple lysine mutations in the C-terminus of p53 make it resistant to degradation mediated by MDM2 but not by human papillomavirus E6 and induce growth inhibition in MDM2-overexpressing cells. 1197 Nov 95

Elevated mortality rates of lung cancer in the Mississippi River corridor in Louisiana have been clearly documented for the past half-century and rank among the highest in the nation. A population-based case-control study of lung cancer termed Lower Mississippi River Interagency Cancer Study was conducted in southern Louisiana. Lung tumor specimens were collected, isolated by laser capture microdissection, subjected to PCR to amplify KRAS, and sequenced to confirm mutation status and specificity. Of the 116 lung tumors analyzed to date, 32 (27.6%) contained mutations in either codon 12 or 13 of KRAS. This frequency is comparable to that reported in the literature; however, the mutation spectrum was strikingly different. Of the 32 mutations observed, 21 (65.6%) resulted in the inappropriate insertion of cysteine, 6 (18.8%) resulted in the insertion of serine, 3 (9.4%) resulted in the insertion of valine, and 1 (3.1%) each resulted in the insertion of aspartate and alanine. These data indicate that an abnormally high proportion of cysteine (P = 0.010) and serine (P = 0.002) mutations was observed in our sample group versus lung cancers reported in the literature. KRAS mutations were more common in African Americans with an odds ratio of 2.4 (P = 0.048), as were serine mutations, although the latter did not reach statistical significance (odds ratio, 2.6; P = 0.373). No association was found between the observed mutation spectrum and known lung cancer risk factors.
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PMID:Differences in KRAS mutation spectrum in lung cancer cases between African Americans and Caucasians after occupational or environmental exposure to known carcinogens. 1243 19

Folate metabolism is thought to play an important role in carcinogenesis through its involvement in both DNA methylation and nucleotide synthesis. A common Ala(222)/Val variant in the methylenetetrahydrofolate reductase (MTHFR) gene leads to a disturbed folate metabolism and is associated with decreased genomic DNA methylation. We previously reported that the MTHFR Val/Val genotype was associated with increased cancer mortality in men from a population-based cohort of subjects ages > or = 85 years. To further explore the deleterious effects of the MTHFR genotype, we studied the association of the genotype with cancer risk in 860 men ages 65-84 years who were followed >10 years (Zutphen Elderly Study). During follow-up, 149 new cases of cancer occurred among the 793 men without cancer at baseline. The risk of developing cancer was 1.80-fold (95% confidence interval, 1.09-3.00) higher among men with the Val/Val genotype than among men with the Ala/Ala genotype. Except for lung cancer [relative risk (RR), 1.15], the risks of common forms of cancers were significantly increased among men with the Val/Val genotype [cancer of the prostate (RR, 3.48); the colorectum (RR, 3.65); the kidney and bladder (RR, 5.48)]. The risks of cancer were particularly increased among men with a lower folate and a higher alcohol intake and men of an older age. In conclusion, our current and previous studies in two independent populations indicate that a common Ala/Val variant in the MTHFR gene is a risk factor for cancer in elderly men from the general population. The mechanism underlying this association might involve genomic instability as a result of insufficient methylation of genomic DNA.
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PMID:A common variant of the methylenetetrahydrofolate reductase gene (1p36) is associated with an increased risk of cancer. 1264 84

Gene methylation and K-ras mutations were examined in tumor and paired serum DNA of 50 resected non-small-cell lung cancer patients. RASSF1A, death associated protein kinase and target of methylation-induced silencing were methylated in 17/50 (34%), 23/50 (45%) and 18/50 (35%) tumors, respectively, and in 17/50 (34%), 20/50 (40%) and 17/50 (34%) sera, respectively. Methylation in tumor and serum were closely correlated (P=0.001), but no correlation was found with survival. Twelve K-ras mutations (cysteine) were found in serum and nine mutations were found in tumor (five cysteine, one alanine, one aspartic, one arginine, and one valine). K-ras mutations in serum correlated significantly with survival (P=0.01).
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PMID:Methylation patterns and K-ras mutations in tumor and paired serum of resected non-small-cell lung cancer patients. 1474 28

A sensitive and specific RP-HPLC assay was developed to measure the levels of polymorphonuclear elastase (PMN-E) activity in growing cell cultures. By combining a pre-incubation of the cells with a relatively non-toxic, PMN-E-specific inhibitor, MeOSuc-Ala-Ala-Pro-Val-chloromethylketone (MAAPVCK), the p-nitroaniline formed by the hydrolysis of the substrate MeOSuc-Ala-Ala-Pro-Val-p-NA by PMN-E is quantified. Elastase-like activity was measured in 14 human cells lines: 13 cancer cell lines (HL-60, U-937, A-427, LCLC-103H, YAPC, DAN-G, PA-TU-8902, KYSE-70, -510, -520, 5637, SISO and MCF-7) and one immortalized epithelial cell line (hTert-RPE1). Activity was detected in all lines; the lowest was found in hTert-RPE1 cells while the highest was detected in a pancreas adenocarcinoma line (PA-TU-8902). When the results were normalized according to cell volume instead of cell number, the leukemia line HL-60 had the highest activity and PA-TU-8902 ranked second. A 1 h pre-incubation with 9.0 microM of the irreversible PMN-E inhibitor MAAPVCK led to varying degrees of enzyme inhibition depending on the cell line; the strongest inhibition was observed with the PA-TU-8902 pancreatic cancer cell line (90% inhibition) while the weakest was seen with the A-427 lung cancer cell line (52%). These results indicate that PA-TU-8902 is a suitable in vitro model for testing the efficacy of PMN-E-activated prodrugs of antitumor agents.
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PMID:Quantification of elastase-like activity in 13 human cancer cell lines and in an immortalized human epithelial cell line by RP-HPLC. 1281 79

The authors imaged a lung cancer patient with an enlarging solitary pulmonary nodule and incidentally found intense activity in the right proximal humerus consistent with known Paget disease confirmed via plain film and computed tomography (CT) without change in the CT appearance or symptoms during the next 7 months. The alkaline phosphatase and alanine amino transferase (ALT) levels were in the normal ranges. Their findings of high uptake with normal alkaline phosphatase and ALT are contradictory to previous reports. The authors present a case of Paget disease that appeared "hot" on positron emission tomography initially thought to be a malignant transformation that typically demonstrated high uptake.
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PMID:Positron emission tomography and Paget disease: hot is not necessarily malignant. 1297 6

Antagonists of human growth hormone-releasing hormone (hGHRH) with increased potency and improved enzymatic and chemical stability are needed for potential clinical applications. We synthesized 21 antagonistic analogs of hGHRH(1-29)NH(2), substituted at positions 8, 9, and 10 of the common core sequence [phenylacetyl-Tyr(1), d-Arg(2,28), para-chloro-phenylalanine 6, Arg(9)/homoarginine 9, Tyr(10)/O-methyltyrosine 10, alpha-aminobutyric acid 15, norleucine 27, Har(29)] hGHRH(1-29)NH(2). Inhibitory effects on hGHRH-induced GH release were evaluated in vitro in a superfused rat pituitary system, as well as in vivo after i.v. injection into rats. The binding affinities of the peptides to pituitary GHRH receptors were also determined. Introduction of para-amidinophenylalanine 10 yielded antagonists JV-1-62 and -63 with the highest activities in vitro and lowest receptor dissociation constants (K(i) = 0.057-0.062 nM). Antagonists JV-1-62 and -63 also exhibited the strongest effect in vivo, significantly (P < 0.05-0.001) inhibiting hGHRH-induced GH release for at least 1 h. Para-aminophenylalanine 10 and O-ethyltyrosine 10 substitutions yielded antagonists potent in vitro, but His(10), 3,3'-diphenylalanine 10, 2-naphthylalanine 10, and cyclohexylalanine 10 modifications were detrimental. Antagonists containing citrulline 9 (in MZ-J-7-72), amidinophenylalanine 9 (in JV-1-65), His(9), d-Arg(9), citrulline 8, Ala(8), d-Ala(8), or alpha-aminobutyric acid 8 substituents also had high activity and receptor affinity in vitro. However, in vitro potencies of analogs with substitution in position 9 correlated poorly with acute endocrine effects in vivo, as exemplified by the weak and/or short inhibitory actions of antagonists JV-1-65 and MZ-J-7-72 on GH release in vivo. Nevertheless, antagonist JV-1-65 was more potent than JV-1-63 in tests on inhibition of the growth of human prostatic and lung cancer lines xenografted into nude mice. This indicates that oncological activity may be based on several mechanisms. hGHRH antagonists with improved efficacy could be useful for treatment of cancers that depend on insulin-like growth factors or GHRH.
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PMID:Increased activity of antagonists of growth hormone-releasing hormone substituted at positions 8, 9, and 10. 1475 56

Using the "one-bead one-peptide" combinatorial technology, a library of random cyclic octapeptides and nonapeptides, consisting of natural and unnatural amino acids, was synthesized on polystyrene beads. This library was used to screen for peptides that promoted attachment and proliferation of bronchioloalveolar carcinoma cells (H1650), employing a "cell growth on bead" assay. Consensus peptide sequences of cNleDXXXXc and cXNleDXXXXc (where Nle is norleucine) were identified. With alanine scanning and site-directed deletion, a typical ligand consisted of a motif of -NleDI/V/Nle- with two flanking cysteines. These peptide ligands were specific for promoting cell attachment of the H1650 cells and the cells of lymphoid cancers (Jurkat and Raji) but not other selected human cell lines of lung cancer and fibroblast. In an antibody blocking assay, integrin alpha(4)beta(1), which was overexpressed in H1650, Jurkat, and Raji, was identified as a putative receptor for these peptide ligands. Using Chinese hamster ovary cells transfected with either wild-type or mutant integrin alpha(4), a critical binding site for these peptides was localized to the glycine residue at position 190 of integrin alpha(4).
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PMID:Novel peptide ligands for integrin alpha 4 beta 1 overexpressed in cancer cells. 1548


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