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

Esophagitis is a major limiting factor in the treatment of lung cancer by radiation alone or in combination with chemotherapy. We have previously demonstrated that intraesophageal injection of manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) complex into C3H/HeNsd mice blocks irradiation-induced esophagitis. To determine whether the human esophagus can be similarly transfected, normal human esophageal sections obtained from the margins of esophagectomy specimens from esophageal cancer patients were transfected in vitro with alkaline phosphatase (AlkP)-PL complex and stained for AlkP activity, and the percent of cells expressing AlkP was calculated. At 24 hr after transfection with 20 or 200 microgram of AlkP-PL complex, 55.0% and 85.8% of esophageal epithelial cells expressed detectable AlkP, respectively. Other sections transfected with MnSOD-PL complex showed transgene mRNA by nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay and increased MnSOD biochemical activity for at least 96 hr after transfection. Irradiated MnSOD-PL complex-transfected sections demonstrated a significantly decreased percentage of apoptotic cells when compared to irradiated control sections. Following 1,000 cGy, MnSOD-PL-treated samples showed 7.5 +/- 2.8% and 33.3 +/- 7.3% apoptotic cells at 24 and 48 hr compared to 53.6 +/- 6.9% and 59.0 +/- 13.8% for nontransfected controls (P < 0.0001 and P < 0.1175). After 2,000 cGy, results at 24 and 48 hr were 25.0 +/- 7.6% and 66.9 +/- 4.9% for MnSOD-transfected sections compared to 65.6 +/- 4.3% and 90.0 +/- 4.1% for control sections (P < 0.0001 and P = 0.0353), respectively. Thus, human esophageal sections can be transfected with MnSOD-PL complex in vitro and thereby protected against ionizing irradiation-induced apoptosis. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 128-137 (2000).
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PMID:Plasmid/liposome transfer of the human manganese superoxide dismutase transgene prevents ionizing irradiation-induced apoptosis in human esophagus organ explant culture. 1090 Apr 24

A newly identified gene, p51, is a functional and structural homologue of the p53 gene and thus a Candidate tumor suppressor gene. To elucidate the role of the p51 gene in lung carcinogenesis, we determined the sequences of exon-intron boundaries and the 5'- and 3'-flanking regions of all the 15 coding exons and performed a mutation analysis, as well as detailed analysis for gene expression. A frameshift mutation was detected in 1 of 44 lung cancer cell lines, whereas no mutation was detected in 45 primary lung cancers. Thus, p51 mutation occurs only in a small subset of lung cancer. Expression of the p51 gene was detected in 23 of 43 cell lines by Northern blot analysis and 34 of 44 by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Thus, p51 expression is low or absent in a subset of lung cancer. The deltaN isotype of p51 transcripts was dominantly expressed in several cell lines, particularly in cell lines with high levels of p51 expression. Because the deltaN isotype encodes a protein that transdominantly suppresses the transactivation function of the TA type of p51, it is possible that p51 protein is not functionally active, even in lung cancer cells with p51 mRNA expression, due to expression of dominant-negative p51 protein. These results suggested that the p51 gene is inactive in a considerable proportion of lung cancers. RT-PCR analysis also revealed the presence of a novel type of mRNA transcript, p51delta, which lacks exons 12 and 13 by alternative splicing. The delta isotype was expressed in 18 of 44 lung cancer cell lines and in diverse normal tissues. Further analysis on p51 expression in cancerous as well as noncancerous cells will provide us with valuable information for the understanding of multiple functions of the p53 family proteins in human carcinogenesis.
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PMID:Mutation and expression of the p51 gene in human lung cancer. 1093 72

The CYFRA 21-1 assay which detects cytokeratin 19 (CK19) fragment is widely used as a tumor marker for lung cancer. However, the reason why some lung cancer cell lines release CK19 fragment in culture supernatants and others do not, remains unclear. It was hypothesized that the release of CK19 fragment may be elucidated by the expression of mRNA for CK19. In order to prove this, the mRNA for CK19 was quantitatively evaluated by the competitive reverse transcriptase-polymerase chain reaction (competitive RT-PCR). The level of CYFRA 21-1 in the culture supernatant was measured by an immunoradiometric assay. CK19 protein synthesis was evaluated by a Western blotting and immunohistochemistry. Fourteen lung cancer cell lines were evaluated, and the amount of mRNA correlated well with the level of CYFRA 21-1 in culture supernatants. Analysis of genomic DNA for CK19 demonstrated that three cell lines which could not produce CYFRA 21-1, conjectured that some abnormalities in exon 1 or the 5'-region upstream from exon 1. In conclusion, it was demonstrated that the release of CK19 fragment was closely related to the expression of mRNA for CK19, and the possibility that genomic change of CK19 DNA down-regulated the expression of mRNA for CK19 was suggested.
Lung Cancer 2000 Oct
PMID:Mechanisms of the release of CYFRA21-1 in human lung cancer cell lines. 1100 10

Cyclooxygenase (COX)-2 has been reported to play an important role in carcinogenesis. Meloxicam (preferential COX-2 inhibitor) inhibits the growth of COX-2 positive and COX-1 negative colorectal cancer cells. We evaluated the effects of meloxicam on the growth of lung cancer cells. By reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis, COX-2 but not COX-1 was expressed in human non-small cell lung cancer (NSCLC) cell lines (A549 and PC14). In human small cell lung cancer (SCLC) cell line (H841), both COX-1 and COX-2 were not detected. MTT assay and prostaglandin (PG) E2 enzyme immunoassay showed that meloxicam inhibited the growth and PGE2 production of both A549 and PC14, but not H841 cells. These findings suggest that COX-2 may play an important role in the pathogenesis and progression of NSCLC, and that meloxicam may be a useful therapeutic agents in the treatment of NSCLC.
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PMID:Meloxicam inhibits the growth of non-small cell lung cancer. 1106 95

The proliferative capability is time-limited in normal somatic cells by the shortening of their chromosomal ends, the telomeres (Hayflick limit). An important feature of malignant cells is their immortality. The probably most common mechanism of tumour cells to achieve unlimited replicability is the activation of the enzyme telomerase. The reverse transcriptase can compensate the loss of telomeres. Using a PCR-based TRAP assay we found telomerase activity in tumour biopsies, exsudates and bronchial washings in various thoracic malignancies. In 38 of 47 patients with suspected peripheral lung cancer eventually surgery or invasive procedures proved a malignancy. In fluoroscopically guided bronchial brushings from 25 of these 38 patients (66%) the TRAP assay revealed telomerase activity. There was a single false positive case (tuberculosis) and with a single exception, the simultaneously taken brushes of the contralateral lobes were all telomerase negative. In 23 patients (61%) tumour cells were found in the cytological examination. In 33 patients at least one marker was positive. Thus the combination of cytology and telomerase test in bronchial brush biopsies attained a diagnostic yield of 87%.
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PMID:[Telomerase in lung cancer. Testing the activity of the "immortaligy enzyme" bronchial biopsies increases the diagnostic yield in cases of suspected peripheral bronchogenic carcinomas]. 1113 43

The CYFRA 21-1 assay, which detects cytokeratin 19 (CK19) fragment, is widely used as a tumor marker for lung cancer, particularly non-small cell lung cancer. However, the reason that some lung cancer cell lines release CYFRA 21-1 in culture supernatants and others do not remains unclear. We hypothesized that the release of CYFRA 21-1 might be related to the expression of CK19 and caspase 3. In order to prove this, the quantities of mRNA for CK19 were evaluated by the competitive reverse transcriptase-polymerase chain reaction (RT-PCR). CK19 protein synthesis was also evaluated by Western blotting and immunohistochemistry, and the levels of CYFRA 21-1 in the culture supernatant were measured by an immunoradiometric assay. The expression of mRNA for caspase 3 was evaluated by the RT-PCR, and caspase 3 protein synthesis was also evaluated by immunohistochemistry. In 13 lung cancer cell lines, the amounts of mRNA for CK19 correlated with the levels of CYFRA 21-1 in culture supernatants, results of Western blotting for CK19, and positivities of immunohistochemistry for CK19. In 5 cell lines that produced a significant amount of CYFRA 21-1, the level of CYFRA 21-1 correlated with the positivity of RT-PCR for caspase 3 and immunohistochmistry for caspase 3. This suggests that caspase 3 played a role in the formation of CYFRA 21-1. In addition, the specific inhibitor of caspase 3 significantly inhibited the release of CYFRA 21-1 in culture supernatants. In conclusion, we demonstrate that caspase 3, which cleaves several intermediate filaments and carries out cell apoptosis, played an important role in producing CYFRA 21-1 in human lung cancer cell lines.
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PMID:The role of caspase 3 in producing cytokeratin 19 fragment (CYFRA21-1) in human lung cancer cell lines. 1125 67

Studies suggest that resveratrol (trans-3,4',5-trihydroxystilbene), which is a diphenolic antioxidant found in plants and foods, has cancer chemopreventive and chemotherapeutic potential. A lower risk of lung cancer among consumers of wine compared with consumers of other beverages has been observed, which may be partly attributed to the high content of resveratrol particularly in red wine. We have studied the effect of resveratrol on the expression of genes involved in the metabolism of polycyclic aromatic hydrocarbons in the human bronchial epithelial cell line BEP2D. Expression of the cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1), microsomal epoxide hydrolase (mEH), and glutathione S-transferase P1 (GSTP1) genes was measured by quantitative reverse transcriptase-polymerase chain reaction. The cells were treated either with benzo[a]pyrene or 2,3,7,8-tetrachlorodibenzo-p-dioxin in the presence or absence of resveratrol. Resveratrol inhibited both the constitutive and the induced expression of CYP1A1 and CYP1B1 in a dose-dependent manner. In contrast, the expression of the mEH gene was increased in response to resveratrol and no change in the expression of GSTP1 was found. The altered gene expression in response to resveratrol was reflected in a reduced overall level of benzo[a]pyrene metabolism. These data indicate that resveratrol may exert lung cancer chemopreventive activity through altering the expression of genes involved in the metabolism of polycyclic aromatic hydrocarbons, resulting in altered formation of carcinogenic benzo[a]pyrene metabolites in human bronchial epithelial cells.
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PMID:Lung carcinogenesis: resveratrol modulates the expression of genes involved in the metabolism of PAH in human bronchial epithelial cells. 1127 1

Small-cell lung cancer (SCLC) synthesises a wide range of neuropeptides and their corresponding receptors. Together, these can form autocrine growth loops. Non-small-cell lung cancer (NSCLC) does not generally share this neuroendocrine phenotype. In this study, we tested the hypothesis that multiple neuropeptides and their receptors are co-expressed in SCLC, constituting potential autocrine loops. Expression of mRNA for arginine vasopressin, gastrin, cholecystokinin, gastrin-releasing peptide, endothelin and neurotensin, together with their cognate receptors, was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) in a panel of human lung cancer cell lines. We have assessed those neuropeptides and neuropeptide receptors that could be used as potential early markers to detect lung cancer cells both as micrometastases in blood and within dysplasia in bronchial biopsies. We establish that although no cell line expressed all neuropeptides, co-expression of neuropeptides and their receptors is common in SCLC but not in NSCLC. We conclude that mRNA for the neuropeptides gastrin-releasing peptide and arginine vasopressin and the cholecystokinin receptor B were most SCLC-specific and RT-PCR for these markers could be used to distinguish between SCLC and NSCLC.
Lung Cancer 2001 Jul
PMID:Use of RT-PCR to detect co-expression of neuropeptides and their receptors in lung cancer. 1142 90

We used our palindromic polymerase chain reaction (PCR)-driven cDNA differential display technique to identify and isolate a gene, designated periostin, from cancer tissues and found it to be overexpressed in several human tumors. We attempted to determine the influence of periostin expression on clinical outcome in patients with non-small cell lung cancer (NSCLC) by reverse transcriptase (RT)-PCR analysis. Periostin gene was highly expressed at the tumor periphery of lung cancer tissue but not within the tumor by in situ RNA hybridization, suggesting that expression of periostin may be involved in the process of tumor invasion. Periostin transcripts were detected in 50 (49.0%) of the tumor samples, although some paired normal lung samples showed weak expression. There was no relationship between periostin gene expression and gender, N- or T-status. The NSCLC patients with periostin expression had significantly poorer survival than the patients without periostin expression (P = 0.0338).
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PMID:Expression of Periostin, homologous with an insect cell adhesion molecule, as a prognostic marker in non-small cell lung cancers. 1150 19

Lung tumors frequently exhibit altered expression of oncogenes and/or tumor suppressor genes. Although some of these alterations are believed to arise from chemical exposure, the ability of specific chemicals to cause distinct changes in gene expression is not well characterized. We previously reported the development of a quantitative reverse transcriptase/polymerase chain reaction (RT/PCR) method for measuring c-myc mRNA levels, and reported that c-myc proto-oncogene expression is significantly increased in small-cell lung carcinoma cells. In the present study, quantitative RT/PCR was used to assess the effect of model toxins cycloheximide (CHX), a protein synthesis inhibitor, and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a DNA alkylating agent, on c-myc mRNA levels in normal human bronchial epithelial (NHBE) and lung adenocarcinoma (A549) cells. Expression of c-myc was evaluated at 1-100 microM CHX and MNNG and was compared to the cytotoxic response as measured by the neutral red assay. Cycloheximide elicited a dose-dependent increase in c-myc mRNA levels in NHBE and A549 cells, but did not alter expression of the housekeeping gene beta-actin. A maximum increase for c-myc expression (200% of control) was observed 5 h after treatment with noncytotoxic concentrations. In contrast, MNNG elicited a dose-dependent decrease in c-myc expression in A549 cells, but no significant change in c-myc was observed in NHBE cells. The results from this study suggest that the quantitative RT/PCR method may be an appropriate technique for monitoring gene expression changes following chemical exposure. Hence, these types of studies may assist in the identification of specific chemicals which may induce the genetic alterations involved in the development of lung cancer as well as provide information relevant to the interactive effects of chemicals within complex mixtures.
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PMID:Quantification of changes in c-myc mRNA levels in normal human bronchial epithelial (NHBE) and lung adenocarcinoma (A549) cells following chemical treatment. 1150 50


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