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)

The polymorphism of mammalian aromatic hydrocarbon (Ah) responsiveness appears to be correlated with genetic differences in risk of bronchogenic carcinoma caused by cigarette smoking. The human polymorphism has been uncovered, largely as the result of corresponding genetic differences characterized first in the mouse. The murine Ah locus has been defined as the gene encoding the aromatic hydrocarbon-responsive (Ah) receptor, responsible for the inducibility of a battery of at least six genes, two of which encode P450 enzymes. The high-affinity receptor and, hence, more highly induced levels of P450, can result in greater concentrations of polycyclic aromatic reactive intermediates that form DNA adducts and, ultimately, mutation fixation (tumour initiation). The Ah receptor is also likely to participate in growth and differentiation signal transduction pathways (tumour promotion). Positive and negative control regions flanking the murine Cyp 1a-1 and human CYP1A1 (cytochrome P(1)450) genes have been identified. A DNA motif approximately 1 kb upstream of the transcription start site appears to affect the translatability of the CYP1A1 mRNA and activity of the enzyme. Expression of the CYP1A1 or CYP1A2 enzyme in mouse hepatoma Hepa-1 cells lacking endogenous CYP1A1 activity represses constitutive transcription of not only the endogenous Cyp1a-1 gene but other genes in the dioxin-inducible [Ah] battery. Human polymorphisms involving a Msp I site 450 bp downstream from the last CYP1A1 exon have been described in Japan, the Eastern Mediterranean, Norway and the USA. The '1.9 allele' is associated with an increased incidence of Kreyberg Type I bronchogenic carcinomas in Japan and has recently been correlated with a valine-to-isoleucine substitution at position 462 in the haeme-binding region. This allele is about 3 times more frequent in Japan than in Caucasians of Norway and the USA, in which no correlation has been found between this allele and lung cancer. More work is needed to clarify these findings. Isolation and sequencing of the human Ah receptor cDNA, and the subsequent screening of populations for polymorphisms, hold great promise for predicting interindividual risk of cancer caused by smoking and other environmental pollutants.
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PMID:Human AH locus polymorphism and cancer: inducibility of CYP1A1 and other genes by combustion products and dioxin. 184 73

A specific member of the cytochrome P450 superfamily of enzymes, designated P450IA (including 2 isozymes, P450IA1 and P450IA2), which is involved in the metabolic activation of polycyclic aromatic hydrocarbons and aromatic amines, was studied in lung tissue from 25 lung cancer patients by immunohistochemistry. The pulmonary activity of a P450IA1-dependent enzyme, aryl hydrocarbon hydroxylase (AHH), from the same patients was also measured. Cytochrome P450IA was localized principally in the peripheral airways in alveolar epithelium of types I and II and in ciliated columnar and cuboidal bronchiolar epithelium. The amount of P450IA in the bronchial wall was minimal and was localized mainly in the capillary endothelium and the epithelium of the bronchial glands. Smoking was the most important factor related to the presence of P450IA and the AHH activity in lung tissue. None of the 10 ex-smokers, but all except I of the current smokers had detectable level of P450IA. The localization of the cancer was also correlated with the presence of cytochrome P450IA. Peripheral lung tissue stained positively in all patients with a peripheral adenocarcinoma who currently smoked (8/8) but in less than half of those with a bronchial cancer who were smokers (3/7). Our data suggest that the smokers who have an inducible cytochrome P450IA are especially at increased risk of developing lung cancer of the peripheral adenocarcinomatous type.
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PMID:Smoking and peripheral type of cancer are related to high levels of pulmonary cytochrome P450IA in lung cancer patients. 184 36

A case of epidural hematoma due to dural metastasis is reported. A 62-year-old man was admitted to our hospital with generalized convulsion. A month prior, he underwent a tumor-removal operation for dural metastasis of lung cancer. CT scan on admission showed an epidural hematoma at the left frontal region. At operation, the epidural hematoma and dural invasion of neoplasm was found and removed. Pathological examination revealed dural metastasis of the poorly differentiated adenocarcinoma. According to the literature, intracranial metastasis of a bronchogenic carcinoma bleeds more often than that of other carcinomas. The particular vascular invasiveness of the neoplasm or a hemorrhagic diathesis is considered as the cause of the hemorrhage. In the present case the pathogenesis of the hemorrhage was thought to be the hypervascularity of the rapid growth tumor, fragility of the tumor vessels, and invasiveness of the tumor into the dural vessels. Adding to these, two other factors could play an important role in forming epidural hematoma; 1) the tumor existed mainly in the epidural surface and 2) dural adhesion of the cranial bone was not so tight.
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PMID:[A case of epidural hematoma due to dural metastasis]. 185 52

The acetylation phenotype was determined, by means of sulfamethazine measurement, in 87 patients (83 male) with confirmed bronchogenic carcinoma and in 93 healthy control patients (41 male) of equal ages. 48 patients and 54 controls were classified as being "slow acetylators" (Ch2 n.s.) When the persons were individually analysed by phenotype, it was confirmed that the patients showed a significantly lower rate of acetylated sulfamethazine than the control group (p less than 0.02), owing to the poor acetylation of patients with small-cell lung cancer. This difference should be confirmed by more detailed pharmacokinetic studies before regarding it as a possible interference of paraneoplasic type. The polymorphism acetylator cannot be considered a genetic marker related to the risk of having lung cancer.
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PMID:[Acetylation polymorphism in lung cancer]. 189 5

The nuclear protein p53 has been measured in archival lung cancer biopsies. The monoclonal antibody PAb 1801, which recognizes human p53, was used. After immunostaining, the nuclei prepared from paraffin-embedded tissue were stained with propidium iodide for simultaneous measurement of DNA content; 17 of 24 lung cancers were p53 positive. The S-phase fraction in positive tumors was 22.9 +/- 6.4%, as compared to 13.6 +/- 6.1% in negative tumors (P less than 0.02). In ten of the positive tumors (two small cell carcinomas and eight non-small cell carcinomas), the p53 expression varied through cell cycle, whereas in seven tumors (five small cell carcinomas and two non-small cell carcinomas), no such variation of p53 expression was observed. Freezing the nuclear suspensions did not substantially reduce the p53 signals. Control experiments with the SV40-transformed human foreskin fibroblast cell line HSF4-T12 showed that the enzymatic digestion utilized to dissociate paraffin-embedded tissue did not significantly reduce p53 fluorescence. Immunohistochemical staining of biopsy specimens indicated that only cancer cells were overexpressing p53. In conclusion, using the monoclonal antibody PAb 1801, p53 is detectable in cell nuclei prepared from paraffin-embedded bronchial carcinoma biopsies. P53 positive tumors have increased proliferative activity compared to p53 negative tumors. Furthermore, the lack of cell cycle variation of p53 in small cell carcinomas indicates that this pattern may be related to high-grade malignancy.
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PMID:Flow cytometric measurement of p53 protein expression and DNA content in paraffin-embedded tissue from bronchial carcinomas. 193 58

The present study has been carried out in order to evaluate the role of tumor markers in the presurgical assessment of patients with bronchial carcinoma. The carcinoembryonic antigen (CEA), the neuron specific enolase (NSE), the tissue polypeptide antigen (TPA), the carbohydrate antigen 19-9 (CA 19-9) and the carbohydrate antigen 50 (CA 50) have been preoperatively measured in 133 subjects with potentially resectable lung cancers, and in 75 healthy smokers. Sixty-one patients had squamous cell carcinoma, 55 adenocarcinoma and 17 small cell carcinoma. Lobectomy (or bilobectomy) was performed in 74 cases, pneumonectomy in 36 cases, exploratory thoracotomy in 15 cases and a palliative resection in 8 cases. When individual markers were considered, TPA showed the highest sensitivity (85%) and CA 19-9 the lowest sensitivity (11%). Specificity was uniformly superior to 90%. When marker associations were considered, the combined measurement of TPA and NSE gave the best results: both the sensitivity and specificity rates approached 90%. The application of the TPA-NSE association allowed detection of 94% of small cell carcinomas, 89% of adenocarcinomas and 85% of squamous cell carcinomas. A positive correlation was found between the complete resectability of lung cancer and serum levels of CEA, CA 50 and CA 19-9. By using the discriminant analysis, a statistical model yielding identification of about 74% of patients with tumors which were judged potentially resectable according to the pre-operative non-invasive diagnostic procedures and were found to be unresectable at thoracotomy, has been get available.
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PMID:[Tumor markers. I. Their significance in the preoperative assessment of lung neoplasms]. 196 95

In 1971-1973 at the third examination of the Basel Study started in 1959, the major antioxidant vitamins and carotene were measured in the plasma of 2974 men. A subsample and their families were reinvestigated in 1977-79. During the 12-y observation period (1973-85) 553 men died, 204 of cancer (lung cancer 68, stomach cancer 20; colon cancer 17, all other malignancies 99). We found significantly lower mean carotene levels for all cancer, bronchus cancer, and stomach cancer (all P less than 0.01) compared with the 2421 survivors. The relative risk of subjects with low carotene (less than 0.23 mumol/L) was significantly elevated (P less than 0.05) for lung cancer (Cox's model). Higher risks were noted for all cancer (P less than 0.01) if both carotene and retinol were low. Low plasma carotene which is known to reflect carotene intake is in our study associated with increased cancer risk.
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PMID:Beta-carotene and cancer prevention: the Basel Study. 198 97

This study evaluates local pulmonary immune effector cell lytic activity. Purified lymphocyte populations were isolated from BALF obtained from 18 patients with bronchogenic carcinoma, six patients with lung disorders other than cancer, and ten normal control volunteers matched for age and smoking history. These cells were evaluated for NK and LAK cell lytic activity against NK-resistant LAK-sensitive tumor targets (A549 pulmonary tumor and Daudi tumor cells) and an NK-sensitive tumor (K562); LAK activity was detected in BALF from 6 of the 18 patients with cancer. The remaining patients with cancer, the subjects with pulmonary disease other than cancer, and the normal volunteers had no detectable lytic activity. Peripheral blood lymphocytes from all subjects had only NK lytic activity and did not kill the pulmonary tumor target; AMs were not tumoricidal. Interleukin-2, which is required for LAK cell activation, was detected only in BALF recovered from the six patients with pulmonary LAK lytic activity. These results demonstrate that activated LAK cells, capable of killing pulmonary tumor cells, are present in BALF of some patients with bronchogenic carcinoma. This lytic LAK cell population represents a local pulmonary response against the lung cancer in the absence of systemic tumoricidal activity. The functional status of pulmonary immune effector cells, as well as the type and quantities of cytokines in the lung determine local responsiveness to bronchogenic carcinoma and may well control the course of this disease.
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PMID:Lymphokine-activated killer cell activity in lung cancer. 198 85

The records of 52 patients younger than 40 years of age who had bronchogenic carcinoma diagnosed between 1965 and 1985 were reviewed. The preponderance of adenocarcinoma (54%), the lower male-female ratio in this age group compared with patients age 40 or older (2:1), the importance of cigarette smoking as a causative factor (80% of patients), the long mean duration of symptoms (5 months), and the high incidence of advanced stage at diagnosis (77% Stages III and IV) in these patients are findings similar to those reported in other published series. There was no significant difference in resectability (23% versus 19%), median survival length (5.3 months versus 6.9 months), median survival length of patients who had surgical resection (10.5 months versus 10.8 months), and 5-year survival rate (11.5% versus 6.3%) in these patients compared with a randomly selected group of 260 patients with lung cancer who were age 40 or older.
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PMID:Lung cancer in patients younger than 40 years of age. 199 10

Plasma antioxidant vitamins A, C, and E and carotene were measured in a group of 2,974 men participating in the third examination of the prospective Basel Study in 1971-1973. In 1985, the vital status and mortality of all participants were assessed. A total of 204 men had died from cancer, including 68 with bronchus cancer and 37 with gastrointestinal cancer (20 with stomach cancer and 17 with large bowel cancer excluding cancer of the rectum). Overall mortality from cancer was associated with low mean plasma levels of carotene adjusted for cholesterol (p less than 0.01) and of vitamin C (p less than 0.01). Bronchus and stomach cancers were associated with a low mean plasma carotene level (p less than 0.01). Subjects with subsequent stomach cancer also had lower mean vitamin C and lipid-adjusted vitamin A levels than did survivors (p less than 0.05). After calculation of the relative risk using the Cox model with exclusion of mortality during the first 2 years of follow-up, low plasma carotene (below quartile 1) was associated with a significantly increased risk for bronchus cancer (relative risk (RR) = 1.8, p less than 0.05), low plasma levels of carotene and vitamin A with all cancers (RR = 2.47, p less than 0.01), and low plasma retinol in older subjects (greater than age 60 years) with lung cancer (RR = 2.17, p less than 0.05). Low levels of vitamin C increased the risk of stomach cancer (RR = 2.38) and gastrointestinal cancer (RR = 2.46) in older subjects, but only significantly with the inclusion of the first 2 years. The authors conclude that low plasma levels of antioxidant vitamins are associated with an increased risk of subsequent cancer mortality. This effect was stronger in men above age 60 years at blood sampling, and the effect seems to be site-specific.
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PMID:Plasma antioxidant vitamins and subsequent cancer mortality in the 12-year follow-up of the prospective Basel Study. 157 Aug 25


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