Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastrin-releasing peptide (GRP) is a 27-amino acid neuroendocrine hormone that may play a role in the pathophysiology of small cell lung carcinoma. GRP and bombesin, a structurally related peptide, stimulate the growth of some cultured cell types. C-terminal GRP peptide analogs were developed that inhibited 6 nM bombesin-induced [3H]thymidine incorporation into quiescent murine Swiss 3T3 cells, which routinely produced a 6-fold stimulation over the basal extent of incorporation. The peptides were also analyzed for their capacity to inhibit the binding of 50 pM 125I-labeled GRP to Swiss 3T3 cells. The combination of two chemical modifications, each antagonistic in itself, led to the creation of antagonists with orders of magnitude greater potency than either modification alone. (i) Antagonist analogs of the form -Leu26-psi(CH2NH)-Xaa27-NH2 [where Xaa is Leu, norleucine (Nle), or Phe; residues numbered after GRP], similar to those introduced by Coy and coworkers [for review, see Jensen, R. T. & Coy, D. H. (1991) Trends Pharmacol. Sci. 12, 13-19], were found to have nanomolar potencies. (ii) We found that an octapeptide C-terminal GRP analog having D-Pro adjacent to the C-terminal amino acid amide was antagonistic, with a potency of 40 nM. By combining both modifications, specific analogs were found with potencies > 1000-fold greater than our lead structure--[(4'-hydroxy)-3-phenylpropanoyl]-Pro-Arg-Gly-Asn-His-Tr p-Ala-Val - Gly-His-Leu-psi(CH2NH)-Nle-NH2--and greater than any antagonist previously reported. The analogs [(4'-hydroxy)-3-phenylpropanoyl]-His-Trp-Ala-Val-D-Ala-His-D-Pro- psi(CH2NH)-Phe-NH2 and 1-naphthoyl-His-Trp-Ala-Val-D-Ala-His-D-Pro-psi(CH2NH)-Phe-NH2 antagonized [3H]thymidine incorporation with IC50 values of approximately 0.3 nM and inhibited the binding of 125I-labeled GRP with IC50 values of approximately 1 pM. These peptides may be of use in the study of the physiology of GRP.
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PMID:Development of potent gastrin-releasing peptide antagonists having a D-Pro-psi(CH2NH)-Phe-NH2 C terminus. 844 10

Lactic acidosis is a rare complication in lung cancer. We report a case of lung cancer accompanied by both syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and lactic acidosis. A 70-year-old man was referred to our hospital for examination of a left hilar mass shadow on a chest X-ray film. Small cell lung cancer (SCLC) was demonstrated by brushing the bronchial mucosa of the left lower lobe bronchus. His laboratory data showed SIADH and lactic acidosis that were probably due to SCLC. Fluid restriction improved SIADH, and combination chemotherapy for SCLC improved the lactic acidosis although the tumor size did not change.
Lung Cancer 1998 Dec
PMID:Small cell lung cancer accompanied by lactic acidosis and syndrome of inappropriate secretion of antidiuretic hormone. 1004 78

A 66-year-old man was admitted with dyspnea on exertion and an abnormal shadow on chest roentgenogram. Transbronchial biopsy yielded a diagnosis of large cell carcinoma of the lung. His dyspnea improved following irradiation and corticosteroid treatment and one month later, he was admitted again for chemotherapy. Because occult blood in stool was detected, upper gastrointestinal endoscopy was performed. Gastric submucosal large cell carcinoma was diagnosed, and this was considered to be metastatic from the lung. Such cases diagnosed prior to death are rare.
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PMID:[Large cell carcinoma of the lung with metastasis of the gastric submucosa]. 1051 14

SULT1A1 enzyme is a member of the sulfotransferase family that alters biological activities of numerous carcinogenic and mutagenic compounds through sulfation. A genetic polymorphism in the coding region of SULT1A1 gene has been associated with modulated enzyme activity. There is a G-->A nucleotide polymorphism in SULT1A1 gene that codes for an Arg-->His substitution, which results in decreased activity and thermal stability of the SULT1A1 enzyme. Utilizing a case-control study design, we hypothesized that the variant allele of the SULT1A1 gene may be associated with lung cancer risk. The PCR-RFLP assay was used to successfully genotype the SULT1A1*2 allele (variant A-allele) in 463 Caucasian lung cancer cases and 485 frequency matched Caucasian controls. There was an overall significant difference between cases and controls when adjusted by sex and smoking status (adjusted OR=1.41, 95% CI: 1.04-1.91). The adjusted OR was higher for females (OR=1.64, 95% CI: 1.06-2.56) than for males (OR=1.23, 95% CI: 0.80-1.88). Furthermore, the risk was significantly higher in current smokers (OR=1.74, 95% CI: 1.08-2.29) and heavy smokers (OR=1.45, 95% CI: 1.05-2.00). Our results support the hypothesis that a genetic polymorphism in the SULT1A1 gene may be associated with increased lung cancer risk.
Lung Cancer 2002 Feb
PMID:Sulfotransferase (SULT) 1A1 polymorphism as a predisposition factor for lung cancer: a case-control analysis. 1180 85

We report here gastric metastasis from lung carcinoma in an 80-year-old man. His chief complaint was epigastric pain from metastases in the stomach. Although metastasis from primary carcinoma of the lung to the small intestine is more common than has been previously suspected, symptoms are rare. Such a metastasis may present as bowel perforation. To find cases of lung carcinoma metastasis to the gastrointestinal tract is clinically rare, and there have been few reports in the English literature. This report describes the gastrointestinal metastasis from lung carcinoma.
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PMID:Gastric metastasis from lung carcinoma. Case report. 1199 51

Lung cancer is a major cause of cancer-related death in the developed countries and the overall survival rate has still an extremely poor. Cigarette smoking is an established risk factor for lung cancer although a possible role for genetic susceptibility in the development of lung cancer has been inferred from familial clustering of the disease and segregation analyzes. Everyone may have a unique combination of polymorphic traits that modify genetic susceptibility and response to drugs, chemicals and carcinogens. Developments in molecular biology have led to growing interest in investigation of biological markers, which may increase predisposition to lung carcinogenesis. Therefore, the high-risk genotype of an individual could be determined easily. As there are the great number of carcinogen-activating and -detoxifying enzymes, the variation in their expression and the complexity of exposures to tobacco carcinogens, the existence of multiple alleles at loci of those enzymes may result in differential susceptibilities of individuals. This review summarize data addressing the relationships of lung cancer to markers of genetic susceptibility genes, including metabolic polymorphisms other than well-investigated cytochrome P450s or glutathione S-transferases, DNA repair genes and the p53 tumor suppressor gene. Among genetic polymorphisms reviewed here, myeloperoxidase gene (a G to A mutation) and microsomal epoxide hydrolase exon 4 polymorphism (substitution of Arg for His) were significantly associated with lung cancer risk. As lung cancer is a multifactorial disease, an improved understanding of the interplay of environmental and genetic polymorphisms at multiple loci may help identify individuals who are at increased risk for lung cancer. Hopefully, in the future we will be able to screen for lung cancer susceptibility by using specific biomarkers.
Lung Cancer 2002 Sep
PMID:Genetic polymorphisms and lung cancer susceptibility: a review. 1223 92

Proline oxidase is a p53-induced gene that can mediate apoptosis in lung carcinoma cells. Here, we provide evidence implicating a role for proline oxidase in renal carcinoma. We observed absent or reduced expression of proline oxidase in 8 of 12 primary renal cell carcinomas, with respect to their normal tissue counterparts. Two renal cell carcinomas, which displayed little or no expression of proline oxidase, expressed p53s that were less capable of inducing proline oxidase than p53 isolated from normal renal tissue. One of those tumor-derived p53s contained a double transition mutation at amino acid residues 125 (Ala to Thr) and 193 (Arg to His), and the other exhibited a single transition mutation at amino acid 149 (Ser to Phe). Forced up-regulation of proline oxidase induced the formation of reactive oxygen species and mediated apoptosis in the 786-0 renal cell carcinoma cell line. A proline oxidase antisense vector repressed p53-induced up-regulation of proline oxidase, release of cytochrome c from mitochondria, and apoptosis in 786-0 renal carcinoma cells. Taken together, these findings support a role for proline oxidase as a downstream effector in p53-mediated apoptosis. We hypothesize that its altered expression can contribute to the development of renal carcinomas. The presence of proline oxidase in mitochondria, a primary organelle that regulates apoptosis, places this molecule in a subcellular localization that can directly influence the apoptotic pathway and thus tumorigenesis.
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PMID:Proline oxidase induces apoptosis in tumor cells, and its expression is frequently absent or reduced in renal carcinomas. 1251 85

Early hilar lung cancer is rare. It is usually curable if properly diagnosed and treated. We recently encountered two cases of early stage squamous cell carcinoma of the left upper division bronchus, which responded well to left upper division sleeve segmentectomy. Case 1 was a 74-year-old man, a heavy smoker, who was referred to our hospital after sputum cytology had resulted in a positive diagnosis while receiving inpatient care for heart failure at another hospital. Bronchoscopy revealed a thickened tumor at the spur between left B(1+2) and B(3). Squamous cell carcinoma was diagnosed by forceps biopsy via bronchoscopy. Left upper division sleeve segmentectomy with lymph node dissection was performed. Since the bronchi to be anastomosed to each other were greatly different in diameter, telescoped anastomosis was used. His postoperative course was uneventful, and he continues to show good respiratory condition, without any evidence of recurrence 25 months after surgery. Case 2 was a 60-year-old man, a heavy smoker, who was identified by sputum cytology as needing detailed examination during a mass screening of high-risk groups for early detection of lung carcinoma. Bronchoscopy revealed a nodular tumor at the orifice of the left upper division bronchus. Squamous cell carcinoma was diagnosed by forceps biopsy via bronchoscopy. Left upper division sleeve segmentectomy with lymph node dissection was performed. During surgery for this case, the lingular bronchus was dissected obliquely to make its cross-section wide enough to match the diameter of the left upper lobe bronchus to which the former was anastomosed. His postoperative course was uneventful, and he shows good respiratory condition, without any evidence of recurrence five months after surgery. The pathological stage was TisN0M0 (stage 0) in both patients, and their tumors were confirmed as early hilar lung cancer. Sleeve segmentectomy, aimed at radical resection of cancer while preserving lung function, can serve as a standard procedure for surgical treatment of cases of early hilar lung cancer confined to the segmental bronchi.
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PMID:Left upper division sleeve segmentectomy for early stage squamous cell carcinoma of the segmental bronchus: report of two cases. 1266 32

Cigarette smoking is the dominant risk factor for lung cancer, but only a minority of smokers ever develops tumors. Though genetic susceptibility is likely to explain some of the variability in risk, results from previous studies of genetic polymorphisms have been inconclusive. As diet may also affect the risk of lung cancer, it is possible that the degree of risk produced by smoking and genetic susceptibility varies, depending on diet. To assess this hypothesis, we conducted a case-control study to examine the effect of cigarette smoking, dietary patterns and variation in genes involved in phase II metabolism. A total of 254 individuals with lung cancer and 184 healthy controls were recruited for the study. To identify persons with similar dietary patterns, cluster analysis was performed using nutrient densities of four major dietary constituents: protein, carbohydrate, animal fat, and dietary fiber. Two groups of individuals were identified with distinct dietary patterns: (1) a group (n=241) with a high intake of animal fat and protein and a low intake of carbohydrates and dietary fiber (the 'unhealthy' pattern) and (2) a group (n=197) with a high intake of fiber and carbohydrate and a low intake of protein and animal fat (the 'healthy' pattern) [corrected]. On stratified analysis, several genotype/dietary pattern combinations were found to affect risk of lung cancer. Smokers who were not homozygous for the most common GSTP1 allele and had a healthy dietary pattern were at significantly lower risk than smokers who were homozygous for the GSTP1 common allele and who had an unhealthy dietary pattern (OR=0.16, 95%CI: 0.04-0.57). Among smokers who were GSTM1 null, persons with a healthy dietary pattern were at lower risk than persons with an unhealthy dietary pattern (OR: 0.46, 95%CI: 0.21-1.01). Among smokers with an unhealthy dietary patterns, persons with a His/His genotype in the exon 3 polymorphism of EPHX1 were at significantly lower risk that persons who were not homozygous. These data suggest that dietary factors may affect the risk imposed by genetic susceptibility at detoxification loci. Adjustments using dietary pattern may be useful in elucidating the effects of polymorphisms in genes responsible for carcinogen metabolism.
Lung Cancer 2003 Sep
PMID:Genetic susceptibility and dietary patterns in lung cancer. 1292 18

Few malignancies have frustrated the persistent efforts of the oncologist like pancreatic cancer. Pancreatic cancer is usually unresectable at the time of diagnosis because of metastasis or local extension. Despite the aggressive nature of this deadly disease, systemic treatment options are limited. Even the recent introduction of the deoxycytidine analogue gemcitabine does not extend median survival of responders beyond a year. Clearly, alternative, more effective regimens are needed for treating pancreatic carcinoma. In pancreatic cancer, there is overexpression of growth factors and growth factor receptors, including epidermal growth factor receptor (EGFR). Targeted toxins consist of a targeting polypeptide covalently linked to a peptide toxin. DAB(389)EGF is a fusion protein composed of the catalytic and translocation domains of diphtheria toxin fused via a His-Ala linker to human epidermal growth factor (EGF). The authors have previously shown that DAB(389)EGF is selectively toxic to EGFR-overexpressing cells, including human brain tumour and lung carcinoma cell lines. Pancreatic adenocarcinoma should be responsive to this fusion protein based on its EGFR overexpression. However, the cytotoxic effect of DAB(389)EGF on human pancreatic carcinoma cell lines has yet to be explored. The authors describe preliminary data showing the potent cytotoxicity of DAB(389)EGF to human pancreatic carcinoma cell lines. Because of the nonspecific toxicity to liver and kidney (which possess EGFR) of systemic administration, they also propose a potential novel drug delivery system for direct toxin implantation into pancreatic tumours using endoscopic ultrasound guided fine-needle injection (EUS-FNI). Hopefully, the use of these targeted therapeutic approaches in combination with other modalities may further extend survival and quality of life in patients with pancreatic adenocarcinoma.
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PMID:Recombinant toxin DAB389EGF is cytotoxic to human pancreatic cancer cells. 1451 80


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