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)

Cell lines derived from human small cell carcinoma of the lung express high levels of a surface polypeptide termed the cluster-w4 antigen, which was previously identified as a potential target for toxin-based immunotherapy of lung cancer. We have cloned a complementary DNA encoding the cluster-w4 antigen from COS-1 fibroblasts transfected with a SW2 small cell carcinoma library, by panning with a mixture of the cluster-w4-specific monoclonal antibodies SWA11, SWA21, and SWA22. The sequence of the cluster-w4 complementary DNA encodes an unusually short (80-amino acid) protein identical to that recently reported for the leukocyte activation molecule CD24 except for a single valine-alanine substitution due to a single-base polymorphism within the region of the gene coding for the extracellular domain. Biochemical analyses of the cloned cluster-w4 antigen confirmed both the presence of the phosphatidylinositol tail and the extensive glycosylation reported for the CD24 molecule. Furthermore, the cloned cluster-w4 antigen expressed on COS cells was shown to react with a comprehensive panel of CD24-specific monoclonal antibodies, as assessed by indirect immunofluorescence staining. Northern blot hybridization indicated the presence of several transcript sizes for the cluster-w4 antigen that were greatly overexpressed in small cell carcinoma cell lines, compared with normal hemopoietic cells and CD24-positive cell lines. Southern blot hybridization of restriction digests of genomic DNA identified a complex pattern of bands consistent with either a complex gene structure containing many exons or the presence of a family of closely related genes.
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PMID:CD24, a signal-transducing molecule expressed on human B cells, is a major surface antigen on small cell lung carcinomas. 132 4

CPT-11, a recently developed topoisomerase I (Topo I) inhibitor, attracts the attention not only of basic researchers but also of clinicians because of its high antitumor activity. The CPT-11 resistant human lung cancer cell line, PC-7/CPT, showed 10-fold resistance compared to parental cell line, PC-7. The total activity of Topo I in the resistant cell line was one fourth that of the parental sensitive cell line. The Topo I from the resistant cells was also 5-fold more resistant to the inhibitory effect of CPT-11 than that of the parental cells. We speculated that the alteration of the Topo I gene may be responsible for the change in topoisomerase activity of the CPT-11 resistant cell line. Therefore, we analyzed the mutation of Topo I gene using the method of single strand conformation polymorphism of polymerase chain reaction and the reverse transcriptase. We divided Topo I cDNA into ten fragments which overlapped each other and covered whole coding sequences of the Topo I cDNA. We observed mobility shift of two fragments in the PC-7/CPT, suggesting the presence of some mutations in these fragments. We performed the direct-sequencing of these portions by the dideoxy chain termination method and observed an altered sequence having a G to A base change in PC-7/CPT. This base substitution results in replacement of the conserved threonine at 729 position with alanine. These results suggest that the point mutation of Topo I gene is related to the decreases of Topo I activity and the sensitivity to Topo I inhibitor in PC-7/CPT cells.
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PMID:Detection of topoisomerase I gene point mutation in CPT-11 resistant lung cancer cell line. 133 3

In this report, point mutations of the K-ras gene at codon 146 were analyzed in 25 cases of colon cancer, 4 cases of lung cancer, and 41 cases of lymphoid malignancy. A codon 146 mutation substituting threonine (ACA) for alanine (GCA) was detected in the tumor tissue of a patient with colon cancer and was not detected in the normal tissue of the same patient. Any additional mutations of the ras gene family were not detected in this patient. These results suggest that the codon 146 mutation of the K-ras gene could be involved in the development of naturally occurring human malignancies.
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PMID:A novel point mutation at codon 146 of the K-ras gene in a human colorectal cancer identified by the polymerase chain reaction. 201 78

4-methoxy-beta-naphthylamide and 7-amino-4-methyl coumarin, derivatives of Z-Ala-Arg-Arg, Leu- and Gly-Phe-beta-naphthylamides were used as substrates in estimation of peptide hydrolases activity in blood serum of patients with malignant tumors and glomerulonephritis in order to ascertain their efficiency for diagnostic purposes in clinic. Each of the fluorogenic substrates studied was hydrolyzed by various peptide hydrolases from blood serum both under normal and pathological conditions: metallopeptidases, cysteine- and serine-dependent peptide hydrolases. The rate of Z-Ala-Arg-Arg-MNA hydrolysis was decreased in lung, kidney and ileum cancer as well as in glomerulonephritis as compared with normal state. The "alkaline-resistant" cysteine-dependent cathepsin B-like proteinase, hydrolyzing this peptide, was not detected in blood serum neither in normal state nor in these diseases studied. Leu-NA and Gly-Phe-NA were hydrolyzed most effectively in blood serum of patients with lung cancer and glomerulonephritis as compared with normal state; cysteine-dependent peptide hydrolases were most markedly activated. Alterations in the enzymatic activity, detected in blood serum, did not exhibit any specificity for definite diseases, they were observed both in malignant and inflammatory impairments. The data obtained suggest that the fluorogenic substrates studied could not be suitable for clinico-diagnostic purposes.
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PMID:[The use of various fluorogenic substrates for determining peptide hydrolase activity of the blood serum]. 266 94

The metabolic changes following thoracic surgery in three groups of patients (esophageal cancer, lung cancer, and hiatus hernia) have been studied. Before operation patients with esophageal cancer, but not those with lung cancer, had significantly lower plasma total protein and albumin than patients with hiatus hernia. After surgery plasma albumin and total protein fell in both esophageal cancer and hiatus hernia patients, a development attributed to poor nutrition and restricted calorie diet in these two groups of patients respectively. With the exception of alanine and arginine in lung cancer patients, and free tryptophan in lung and esophageal cancer patients, the preoperative concentrations of all plasma amino acids were similar in both groups of cancer patients and in those with hiatus hernia. After operation the concentrations of glutamine, total tryptophan, alanine, glycine, and arginine fell sharply, whereas those of phenylalanine, lysine, valine, and leucine were slightly or not at all affected by surgery. The immediate postoperative fall of plasma free amino acids is thought to be due to the increased rate of gluconeogenesis. The rise of free fraction of plasma tryptophan after surgery is related to the raised level of plasma free fatty acids and increased secretions of catecholamines, which is believed to follow surgery.
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PMID:Preoperative and postoperative levels of plasma protein and amino acid in esophageal and lung cancer patients. 338 36

Many malnourished patients with cancer fail to gain weight with what appears to be adequate nutritional support. Metabolic abnormalities resulting from remote effects of the tumor on host metabolism have been postulated to increase energy requirements in such cancer patients. In the current study, 44 patients with lung cancer who had significant weight loss (16 +/- 2% of usual body weight) were studied under metabolic ward conditions. Whole body glucose production rates were significantly elevated in cancer patients compared to age-matched healthy controls. Blood glucose levels 2 hours after a standard oral glucose challenge were also significantly increased, but insulin levels were not different at this time. Fasting glucose and insulin levels were not different. Fasting plasma alanine levels were significantly decreased in these patients, while branched-chain amino acids were not different. Increased alanine flux for gluconeogenesis is likely to reflect a basic metabolic abnormality in patients with cancer and could be explained on the basis of a resistance to insulin action in such patients.
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PMID:Metabolic abnormalities in the cancer patient. 388 Jun 55

A study of arterial and arterio-venous amino acid concentration differences across the forearm was performed in 19 weight-losing cancer (CWL) patients (9 with lung cancer and 10 with other types of cancer), 8 weight-losing patients with active pulmonary tuberculosis (TWL) and 10 normal controls. Arterial concentrations of many of the amino acids measured were found to be lower in CWL than in TWL patients. In addition, the data suggested a venous excess of amino acids in the CWL patients compared with TWL patients and controls. The increased release of alanine from forearm muscles in the CWL group, together with the low arterial glycogenic amino acid levels, supports the concept of enhanced gluconeogenesis in CWL patients. Low arterial amino acid levels and possible increased release of amino acids from forearm muscle in CWL patients implies enhanced proteolysis with increased central clearance or tumour sequestration of these amino acids, though decreased proteogenesis cannot be excluded in accounting for the venous excesses in this group. Hypocitrullinemia in lung cancer patients was marked, and possible mechanisms to account for this are discussed.
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PMID:Serum amino acids in weight-losing patients with cancer and tuberculosis. 668 43

Using proton magnetic resonance spectroscopy (1H MRS) spectra were obtained in vitro from extracts of four types of lung cancer (squamous cell, adenocarcinoma, large cell, small cell) and normal lung. The hydrophilic phase of the chloroform/methanol-water extracts yielded several distinct peaks. Among them the peak areas for cholines, creatines, glycine, and alanine, and their ratios were calculated and used as parameters to characterize different lung tissues. The ratios, cholines/alanine and glycine/alanine, were significantly (P < 0.001 to P < 0.05) higher for the normal lung than lung cancers. Creatines/glycine and creatines/cholines generally provided good discrimination (P < 0.001 to P < 0.05) between any two types of lung cancer. When data were further analyzed by discriminant factor analysis, there was 81.5 to 90.7% accuracy in predicting between normal lung and each cancer type, or among the four types of lung cancer. These results suggested that 1H MRS might be useful as an adjunct modality in the differential diagnosis of lung cancers.
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PMID:In vitro characterization of lung cancers by the use of 1H nuclear magnetic resonance spectroscopy of tissue extracts and discriminant factor analysis. 838 59

We conducted a phase I and pharmacokinetic study of the topoisomerase II catalytic inhibitor fostriecin. Fostriecin was administered intravenously over 60 min on days 1-5 at 4-week intervals. Dose was escalated from 2 mg m(-2) day(-1) to 20 mg m(-2) day(-1) in 20 patients. Drug pharmacokinetics was analysed with high performance liquid chromatography with UV-detection. Plasma collected during drug administration was tested in vitro for growth inhibition of a teniposide-resistant small-cell lung cancer (SCLC) cell line. The predominant toxicities were elevated liver transaminases (maximum common toxicity criteria (CTC) grade 4) and serum creatinine (maximum CTC grade 2). These showed only a limited increase with increasing doses, often recovered during drug administration and were fully reversible. Duration of elevated alanine-amino transferase (ALT) was dose-limiting in one patient at 20 mg m(-2). Other frequent toxicities were grade 1-2 nausea/vomiting, fever and mild fatigue. Mean fostriecin plasma half-life was 0.36 h (initial; 95% CI, 0-0.76 h) and 1.51 h (terminal; 95% CI, 0.41-2.61 h). A metabolite, most probably dephosphorylated fostriecin, was detected in plasma and urine. No tumour responses were observed, but the plasma concentrations reached in the patients were insufficient to induce significant growth inhibition in vitro. The maximum tolerated dose (MTD) has not been reached, because drug supply was stopped at the 20 mg m(-2) dose level. However, further escalation seems possible and is warranted to achieve potentially effective drug levels. Fostriecin has a short plasma half-life and longer duration of infusion should be considered.
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PMID:Phase I and pharmacokinetic study of the topoisomerase II catalytic inhibitor fostriecin. 1007 Aug 85

We previously reported the presence of mitotic check-point impairment in about 40% of lung cancer cell lines. To gain an insight into the molecular basis of this impairment, we examined 49 lung cancer specimens for alterations in the hMAD1 mitotic checkpoint gene and identified a somatic, non-conservative missense mutation, which substitutes alanine (GCG) for threonine (ACG) at codon 299, together with a number of amino acid substituting, single nucleotide polymorphisms. This is the first demonstration of hMAD1 mutation in any type of human cancers. The present finding marks hMAD1 as a potential target, although with low frequency, for genetic alterations in lung cancer. Thus, further studies of hMAD1 dysfunction caused by other mechanisms appear to be warranted, as well as potential involvement of other components of the mitotic checkpoint.
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PMID:Search for in vivo somatic mutations in the mitotic checkpoint gene, hMAD1, in human lung cancers. 1059 20


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