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)

A human lung tumor-associated fetal antigen (LTFA) has been partially isolated and characterized. The antigen that differs in several immunochemical parameters from previously described lung cancer antigens was shared by fetal lung and liver tissue. The neoantigen migrated in immunoelectrophoresis as an alpha2-beta globulin, had an average molecular size of 7S, and was soluble in 50% saturated ammonium sulfate. Whereas LTFA was insensitive to both DNase and RNase treatment, its antigenicity was completely abolished by pronase. The biologic significance of this antigen and its possible clinical use were discussed.
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PMID:Partial characterization of a fetal lung antigen associated with human bronchogenic carcinoma. 10 44

Serum ribonuclease levels were determined in 54 patients with lung carcinoma, 74 long-term cigarette smokers, and 172 nonsmokers. The mean serum ribonuclease level was significantly higher in patients with lung carcinoma and long-term smokers compared with healthy nonsmokers (P less than .001). The serum ribonuclease activity level was not related to chronological age, sex, or race of the smoker or nonsmoker population. Forty (75%) of 53 patients with lung cancer and 49 (66%) of 74 smokers had elevated serum ribonuclease levels compared with 13 (7%) of 179 nonsmoker healthy controls (P less than .001). The highest incidence of elevation was noted in patients with epidermoid carcinoma (95%).
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PMID:Carcinoma of the lung and cigarette smoking. Effect on serum ribonuclease activity. 20 37

Serum RNase (ribonuclease) of normal persons and of patients with pancreatitis, carcinoma of pancreas, or other neoplasms was determined with poly(C) as substrate. Strikingly abnormal elevations occur in the serum RNase of patients with pancreatic cancer. There is no elevation in the serum RNase level of patients with pancreatitis. Average serum RNase values of 52 normal persons, 10 patients with pancreatitis, 30 patients with pancreatic cancer, 28 patients with breast cancer, 11 patients with lung cancer, 20 patients with colon cancer, six patients with stomach cancer, and four patients with liver cancer, respectively, were 104, 120, 383, 131, 173, 197, 194, and 152 units/ml of serum. Ninety percent of the patients with pancreatic cancer were above the level of 250 units of serum and 90% of all patients with varied cancers were below this level. In the presence of severe renal insufficiency, marked elevation of serum RNase was also observed. Serum RNase, because of its unique specificity, pancreatic origin, and its abnormal elevation in sera of patients with pancreatic cancer, serves as a reliable biochemical marker of carcinoma of the pancreas in the presence of normal renal function.
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PMID:Elevated serum ribonuclease in patients with pancreatic cancer. 106 80

The p53 gene initially was thought to be an oncogene, but recent evidence suggests that wild-type p53 can function as a tumor suppressor gene in lung, colon, and breast cancer as well as less common malignancies. This study reports the first identification of intronic point mutations as a mechanism for inactivation of the p53 tumor suppressor gene. Abnormally sized p53 mRNAs found in a small cell and a non-small cell lung cancer cell line were characterized by sequence analysis of cDNA/PCR products, the RNase protection assay and immunoprecipitation. These mRNAs were found to represent aberrant splicing leading to the production of abnormal or no p53 protein. Sequence analysis of genomic DNA revealed that a point mutation at the splice acceptor site in the third intron or the splice donor site in the seventh intron accounts for the abnormal mRNA splicing. In one patient the same intronic point mutation was found in the tumor cell line derived from a bone marrow metastasis and in multiple liver metastases but not in normal DNA, indicating that it occurred as a somatic event before the development of these metastases. These findings further support the role of inactivation of the p53 gene in the pathogenesis of lung cancer and indicate the role of intronic point mutation in this process.
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PMID:Identification of intronic point mutations as an alternative mechanism for p53 inactivation in lung cancer. 216 47

Point mutations in genes can be etiologic of pulmonary diseases, as in the case of the inherited disorders alpha-1-antitrypsin deficiency and cystic fibrosis or in the context of dominant and recessive oncogenes in lung cancer. Various methodologies have been developed to screen for single-base mutations. These techniques include direct DNA sequencing, RNase protection, denaturing gradient gel electrophoresis, and chemical mismatch cleavage. The latter method offers the advantages of rapid and efficient analysis of genomic or cDNA and is thus ideally suited to screening applications. Furthermore, all possible single-base changes can theoretically be detected. In the present work, chemical mismatch cleavage was utilized to detect mutations in the p53 gene in small cell and non-small cell lung cancer. This technique was modified by using a two-step, hemi-nested PCR procedure for preparation of target genomic DNAs permitting an expanded target size for analysis. Evaluation by chemical mismatch cleavage of eight p53 cDNAs derived from lung tumors shown to have different mutations by DNA sequencing correctly detected the presence of a point mutation in all instances. Analysis of six additional tumor genomic DNAs with defined mutations in the corresponding p53 cDNAs accurately confirmed the mutation at the level of the genome. The technique also identified codon 72 and intron 6 polymorphisms. Using the intron 6 polymorphism, loss of heterozygosity at the p53 locus in tumor DNA was readily detected by chemical mismatch cleavage. Finally, utilizing this technique for scanning analysis of the p53 gene of uncharacterized lung tumor DNAs, additional mutations were identified in a prospective manner which were confirmed by sequence analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A chemical mismatch cleavage method useful for the detection of point mutations in the p53 gene in lung cancer. 222 98

The influence of a variety of clinical and biochemical parameters on the activities in serum of ribonuclease (RNAse) selective for polycytidylic acid (RNAse C) were examined in 90 adult patients with cancer. The clinical data base determined on each patient included: RNAse C level, carcinoembryonic antigen (CEA) level, age, sex, race, presence (or absence of metastases, type of cancer, site of metastasis, renal function blood urea nitrogen [BUN], creatinine), hepatic function (bilirubin, alkaline phosphatase), and nutritional status (percent ideal body weight, percent weight loss, and albumin). Common tumor types studied included: colon (21), lung (18), breast (15), and hepatocellular carcinoma (10). For comparison, 175 nonmalignant control patients were studied to establish the normal range for RNAse. In patients with cancer, RNAse levels were increased in 57% and CEA levels were above 10 ng/dl in 36%. Although patients with BUN greater than 25 mg/dl or creatinine greater than 1.5 mg/dl were not entered on the study, nonetheless, RNAse was significantly (P less than 0.05) associated with both BUN and creatinine. Nutritional status also had an important influence on RNAse levels as both percent weight loss and percent ideal body weight were significantly (P less than 0.05) associated with circulatory RNAse: weight loss resulted in higher RNAse levels. These results account in part for the increased RNAse levels seen in those malignant conditions such as pancreatic and lung cancer commonly associated with weight loss in advanced stage. The possibility that circulatory RNAse C determination will provide a sensitive means for assessing nutritional status in cancer patients will require prospective evaluation.
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PMID:Influence of nutritional status on circulatory ribonuclease C levels in patients with cancer. 298 Nov 45

We have found growth-promoting activity for vascular endothelial cells in the conditioned medium of a human lung cancer cell line, T3M-11. Purification and characterization of the growth-promoting activity have been carried out using ammonium sulfate precipitation and gel-exclusion chromatography. The activity migrated as a single peak just after ribonuclease. It did not bind to a heparin affinity column. These results suggest that the activity is not a heparin-binding growth factor (including fibroblast growth factors) or a vascular endothelial growth factor. To identify the molecule exhibiting the growth-promoting activity, a cDNA encoding the growth factor was isolated through functional expression cloning in COS-1 cells from a cDNA library prepared from T3M-11 cells. The nucleotide sequence encoded by the cDNA proved to be identical with that of insulin-like growth factor II.
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PMID:Isolation of a cDNA for a growth factor of vascular endothelial cells from human lung cancer cells: its identity with insulin-like growth factor II. 773 Jan 45

Cytochrome P450 (CYP) enzymes expressed in human lung can metabolize a variety of xenobiotics, drugs, and endogenous compounds. Metabolism of these substrates may lead to their detoxification or activation and may affect the homeostasis of the lung, its susceptibility to disease, response to therapy, and clinical prognosis. We analyzed the expression of CYP2B7, CYP4B1, and NADPH-cytochrome P450 oxidoreductase (OR) mRNAs in normal lung controls, normal lung from lung cancer patients, and lung tumors using the sensitive technique of RNase protection. The mRNAs of CYP2B7, CYP4B1, and OR were detected in all the normal and a majority of neoplastic tissues. The three mRNAs were quantified and found at an average ratio of 0.89, 4.03, and 0.88% relative to actin mRNA in normal lung, respectively. There was no correlation between the levels of expression of the three mRNAs and the histological diagnosis of tumors. The amounts of each of the three mRNAs varied considerably between patients, but analysis of frequency distribution of the levels of CYP2B7 and CYP4B1 mRNAs did not present evidence for genetic polymorphism as a possible source of the observed interindividual variability. Levels of expression of the two P450 mRNAs were reduced (2.3- and 2.4-fold) in the neoplasms compared to normal lung. The level of OR mRNA expression was uniform with no significant differences between normal and neoplastic tissues, and its interindividual variability was the lowest amongst the three mRNAs studied. All mRNAs had increased interindividual variability in neoplastic tissues. Analysis of the patients' smoking histories and the level of CYP2B7, CYP4B1, and OR mRNAs revealed no evidence for their induction by compounds present in cigarette smoke. This study identifies and characterizes lung and lung tumor mRNAs encoding enzymes that may participate in the metabolism of xenobiotics in humans.
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PMID:Quantification of CYP2B7, CYP4B1, and CYPOR messenger RNAs in normal human lung and lung tumors. 831 65

Human cells can become multidrug resistant (MDR) by an increase in the activity of the MDR1 P-glycoprotein or by other, as yet unknown mechanisms, referred to as non-P-glycoprotein mediated MDR (non-Pgp MDR). S. P. C. Cole et al. [Science (Washington DC), 258: 1650-1654, 1992] recently reported that in two cell lines non-Pgp MDR was associated with the overexpression of a new putative membrane transporter gene, MRP. Using an RNase protection assay we have analyzed the expression of MRP in non-Pgp MDR sublines of the human lung cancer cell lines SW-1573 (non-small cell lung cancer) and GLC4 (small cell lung cancer). In all of ten SW-1573 derived lines examined the MRP mRNA level was equal to that in the parental line, whereas MRP was 25-fold overexpressed in a resistant subline of GLC4. We conclude that overexpression of MRP cannot account for all forms of non-Pgp MDR.
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PMID:Analysis of the expression of MRP, the gene for a new putative transmembrane drug transporter, in human multidrug resistant lung cancer cell lines. 846 91

The multidrug resistance-associated protein (MRP), a new membrane transporter related to non-Pgp multidrug resistance, is overexpressed in some drug-selected cancer-cell lines. The role of MRP in unselected cell lines and in human cancer is unknown. MRP gene expression, determined by RNase protection assay and chemosensitivity to doxorubicin, etoposide and cisplatin, determined by MTT assay, were assessed in 18 non-drug-selected lung-cancer cell lines (10 small-cell lung cancer, 6 non-small-cell lung cancer, and 1 carcinoid). MRP gene expression was also investigated in normal lung tissue and primary non-small-cell lung cancer. All cell lines except one and all normal lung tissues and primary non-small-cell lung cancers expressed detectable levels of MRP. Expression was significantly lower in cell lines than in normal and neoplastic lung. MRP protein expression was also assessed by immunohistochemistry using the monoclonal antibody MRPr1; comparable levels of expression were observed between mRNA and protein in cell lines; however, in tumor samples intense staining was observed in tumor cells as well as in infiltrating normal cells in tumors, making the results less comparable to those obtained by RNase expression. MRP expression did not directly correlate with function in a calcein accumulation assay in 2 unselected cell lines. No gene amplification was observed by Southern-blot analysis, in the unselected cell lines or in tumor samples. In general, in cell lines, MRP gene expression was correlated with lower chemosensitivity to doxorubicin and etoposide, but not to cisplatin. However, MRP expression did not directly correlate with MRP function as assessed by a calcein accumulation assay in one of 2 unselected cell lines examined. Our results suggest that MRP may be implicated in drug resistance in unselected lung-cancer cell lines and its role in normal lung and primary lung cancer warrants further investigation in patients undergoing chemotherapy.
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PMID:MRP is frequently expressed in human lung-cancer cell lines, in non-small-cell lung cancer and in normal lungs. 864 46


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