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)

Adducts, formed by carcinogens of tobacco smoke with DNA, can be detected by means of molecular techniques and are used as marker of internal exposure. Carcinogen-DNA adducts produce specific mutations in tumor-suppressor genes (e.g. p53) and oncogenes (e.g. ras), which can be involved in tumor initiation or in later stages of tumor progression (e.g. evolution of an invasive phenotype). Benzo(a)-pyrene, an important carcinogen of tobacco smoke, induces GT transversions, as demonstrated in in vitro systems and animal models. Mutations in the p53- or ras-gene are more common in human tumors of the lung, head and neck, bladder and pancreas in smokers than in non-smokers. Molecular biology of cancer gains increasing significance in clinical practice since 1.) the presence of certain mutations confers an unfavorable prognosis to malignant disease (e.g. ras mutations in lung cancer), 2.) ras and p53 mutations often occur early during tumor development and can thus facilitate diagnosis of malignant disease, and 3.) minimal residual disease can be detected using molecular techniques. After resection of cancer of the head and neck, tumor recurred more frequently in patients with no evidence of residual disease as assessed by pathohistologic criteria than in patients with no evidence of residual disease as evaluated by p53 immunostaining.
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PMID:[Molecular biology of tobacco smoke associated neoplasia]. 901 41

Small-cell lung cancer (SCLC) represents a group of highly malignant tumors giving rise to early and widespread metastases. We used comparative genomic hybridization in autoptic tumor specimens from 10 patients to discover genetic alterations that are associated with tumor progression and potentially with the metastatic phenotype. Ten primary SCLC and 16 corresponding metastases were investigated with a maximum of 4 tumors per case. Prevalent changes observed in more than 60% of the primary tumors and their metastases included deletions on chromosomes 3p, 4q, 5q, 10q, 13q and 17p, and DNA over-representations on chromosomes 3q and 5p. The number of common alterations in the primary tumors and the related metastases outnumbered the differences, indicating a clonal relationship. Within the lesions of the same patient, differences were found between the primary tumor and the metastases as well as between metastases of distinct organ sites. However, no specific alteration was significantly associated with the metastatic phenotype. We suggest that the high malignancy of SCLC is defined by the above-mentioned pattern of aberrations.
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PMID:Primary small-cell lung carcinomas and their metastases are characterized by a recurrent pattern of genetic alterations. 903 75

Human P-glycoprotein (Pgp) encoded by the MDR1 gene confers multidrug resistance to cancer cells. The clinical role of MDR1/Pgp in lung cancer is not fully understood. A total of 87 lung cancer surgical tissue samples, including previously untreated 84 non-small-cell (NSCLC) and three small-cell lung carcinoma (SCLC), were analyzed for levels of MDR1 mRNA determined by Northern blotting and compared with MDR1-positive cell lines. Fifteen percent (13/87) of the tumors were positive for the MDR1 gene, but the level was low in all samples except in one adenocarcinoma which expressed a high level of MDR1. The gene expression in these tumors did not relate with any pathologic factors such as histologic type, pathologic stage and tumor size. The SCLC and only one of the 14 MDR1-negative NSCLC responded to adjuvant chemotherapy after surgery. The present results indicate that the MDR1 gene is not associated in NSCLC with tumor progression and drug resistance.
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PMID:The clinical role of MDR1 gene expression in human lung cancer. 906 8

Motility-related protein-1 (MRP-1)/CD9 is a trans-membrane glycoprotein closely associated with suppression of cell motility and reduced metastatic potential of some tumor cells. We currently report that, according to the RT-PCR method for MRP-1/CD9 gene expression, patients with low expression of MRP-1/CD9 in non-small-cell lung cancer, especially the adenocarcinoma type, showed short overall survival. Then, to determine accurately the prognostic value of MRP-1/CD9 product levels in lung-adenocarcinoma cells, we immunohistochemically investigated its expression in 132 lung-adenocarcinoma patients undergoing potentially curative surgery. Of these patients, 44 (33%) showed reduced expression of MRP-1/CD9 in cancer cells, and an inverse association was observed between its expression and factors associated with tumor progression, such as nodal involvement (p = 0.029) or stage (p = 0.028). Patients with reduced expression of MRP-1/CD9 showed a significantly worse prognosis in overall survival (p = 0.005) and disease-free survival (DFS; p < 0.0001) than those with stronger expression; and even among patients with stage-I disease, similar results were obtained (overall survival, p = 0.038; DFS, p = 0.012). In a multivariate analysis, immunohistochemical MRP-1/CD9-expression level was an independent prognostic factor for DFS (p = 0.021), but not for overall survival (p = 0.572). Thus, immunohistochemical MRP-1/CD9-expression level solely in lung-adenocarcinoma cells within the tumor tissue appears to be a prognostic factor for DFS, and may be useful for detecting a high-risk sub-group of recurrence during the post-operative clinical course of the disease.
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PMID:Immunohistochemically detected expression of motility-related protein-1 (MRP-1/CD9) in lung adenocarcinoma and its relation to prognosis. 913 57

Restriction fragment length polymorphism in the human c-Ha-ras-1 locus, associated with a minisatellite sequence, was examined in 45 multiple primary cancer (MPC) patients, 56 patients with squamous cell lung cancer (SCLC), 21 patients with lung adenocarcinoma (LAC), and 53 individuals having no oncopathology. Southern analysis of cellular DNA revealed the presence of 4 common alleles (with collective allele frequency close to 94% in the control group) and a set of rare alleles. Allele a3, (2.1 kb in size under MspI/HpaII digestion) was shown to be more frequent in the MPC than in the control group. The same tendency was observed in the patients with highly differentiated cell lung cancer. An increased frequency of the a4 allele (2.5 kb under MspI/HpaII digestion) was observed in the patients with adenocarcinomas as well as in the patients with metastases and low levels of tumor tissue differentiation. The elevated frequencies of a3 in the MPC group and of a4 in the LAC patients did not correlate with increased risk of the cancers mentioned above but was associated with type of tumor progression. Previously, it was reported that the mini-satellite sequence within the c-Ha-ras-1 locus possesses enhancer activity. Our data indirectly confirm the hypothesis that the efficiency of minisatellite modulator activity is associated with fragment size.
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PMID:[Restriction polymorphism of the proto-oncogene c-Ha-ras-1 in patients with multiple primary malignant neoplasms and non-small-cell lung cancer]. 916 92

The growing asthenia of the neuro-psychic system which frequently occurs in cancer patients, particularly, in the preoperative period might undermine the body's defenses and thus contribute to tumor progression. The psycho-emotional system and immunological status of lung cancer patients were corrected with a combination of measures including individual psychotherapy and tranquilizer treatment. A study of blood levels of PI, PIP, PG-F and PG-E2 as well as the use of a number of methods of psychological diagnosis showed that the psycho-emotional and immunological status improves as a result of such preoperative therapy.
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PMID:[Correlation of psychoemotional state and membrane condition in patients with lung cancer in the preoperative period]. 921 14

Lung cancer is a major contributor to overall cancer mortality. Detecting lung cancer while it is still a localized process is a long-cherished goal for improving the outcome of this disease. Recent developments suggest that we are approaching this capability. We next have to think about how to implement a change in our approach to lung cancer management to derive the benefit of better detection capability. This is an area in which our growing understanding of lung cancer biology is providing clues on improving the inhibition of cancer progression.
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PMID:Recent molecular advances in the approach to early lung cancer detection and intervention. 925 84

Metastasis is the ultimate life-threatening stage of cancer. The lack of accurate model systems thwarted studies of the metastatic cell's basic biology. To follow continuously the succeeding stages of metastatic colony growth, we heritably labeled cells from the human lung adenocarcinoma cell line ANIP 973 with green fluorescent protein (GFP) by transfection with GFP cDNA. Labeled cells were then injected intravenously into nude mice, where, by 7 days, they formed brilliantly fluorescing metastatic colonies on mouse lung [Chishima, T., Miyagi, Y., Wang, X., Yang, M., Tan, Y., Shimada, H., Moossa, A. R. & Hoffman, R. M. (1997) Clin. Exp. Metastasis 15, 547-552]. The seeded lung tissue was then excised and incubated in the three-dimensional sponge-gel-matrix-supported histoculture that maintained the critical features of progressive in vivo tumor colonization while allowing continuous access for measurement and manipulation. Tumor progression was continuously visualized by GFP fluorescence in the same individual cultures over a 52-day period, during which the tumors spread throughout the lung. Histoculture tumor colonization was selective for lung cancer cells to grow on lung tissue, because no growth occurred on histocultured mouse liver tissue, which was also observed in vivo. The ability to support selective organ colonization in histoculture and visualize tumor progression by GFP fluorescence allows the in vitro study of the governing processes of metastasis [Kuo, T.-H., Kubota, T., Watanbe, M., Furukawa, T., Teramoto, T., Ishibiki, K., Kitajima, M., Moossa, A. R., Penman, S. & Hoffman, R. M. (1995) Proc. Natl. Acad. Sci. USA 92, 12085-12089]. The results presented here provide significant, new opportunities to understand and to develop treatments that prevent and possibly reverse metastasis.
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PMID:Governing step of metastasis visualized in vitro. 932 51

The purpose of this study was to assess the possible benefit of adjuvant spleen ultrafiltrate immunotherapy in advanced lung cancer patients on chemotherapy. Twenty-six patients with inoperable non-small cell lung carcinoma were eligible to this study and randomised divided into two groups. The two groups received additionally to standard chemotherapy--three times once a month--placebo or spleen ultrafiltrate (Prosplen), respectively, given to the patients for 14 days beginning from the 7th day after each chemotherapy. To evaluate the effects of spleen ultrafiltrate, the time of haematological recovery and profile of peripheral blood lymphocytes and clinically number of days with fever and oncological response were documented. During the observation time patients receiving spleen ultrafiltrate had a higher number of leukocytes (p = 0.01) and higher counts (p = 0.03) and percentage of granulocytes (p < 0.001) including nadir values (p = 0.05) in blood. The positive effect was also seen in natural killer cells (p = 0.005) but not in T cells compartment. This could be of clinical significance because patients receiving spleen ultrafiltrate presented less frequently febrile episodes than patients in the placebo group (75 vs. 127 days with body temperature > 38 degrees C, p = 0.007) and had less frequently highly elevated serum C-reactive-protein levels (p = 0.02). Notably, 2 out of 12 patients receiving in addition to chemotherapy spleen ultrafiltrate and 7 out of 14 lacking this adjuvant treatment showed tumor progression during the treatment. Serum C3 levels were associated with progression of disease in both groups (p = 0.03). Overall, spleen ultrafiltrate receiving patients had lower serum C3 values than placebo receiving patients. Serum IgM levels were rather high in the placebo group (p = 0.033). Spleen ultrafiltrate is thought to benefit patients on palliative chemotherapy in advanced metastatic cancers.
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PMID:Adjuvant spleen ultrafiltrate immunotherapy in unresectable advanced non small cell lung cancer. 945 Jan 74

Differentiated thyroid cancers account for 1% of all neoplasias but only for 2.3% of thyroid nodules. A particular condition is represented by the association with hyperthyroidism, which is found in about 7% of cases. Even more rarely may be themselves cause of thyrotoxicosis. In the present paper, the case of a 66-year old male patient, bearing a recently appeared goiter, referred to us for suspicion of lung cancer and hyperthyroid symptoms, is reported. Among appropriate investigations, the finding of high titer of thyroglobulin in the aspiration needle and cytology examination suggested that thyroid lesion was primary and not metastatic, while scintiscan with J-131 isotope showed that excess of thyroid hormones was just due to it; histological diagnosis was of papillary carcinoma. As to the pathogenesis of the neoplasma during hyperthyroidism, a causal role of thyroid stimulating auto-antibodies has been suggested in the cases associated with Graves' disease, absent in our patient, which could elicitate cancer progression in the mean time. Interestingly, activating mutation of thyroid hormone receptor (TSH-r) gene has been demonstrated in a hyperfunctioning differentiated cancer. Notwithstanding the unexpected clinical behaviour may appear very rare, molecular biology studies on aspiration biopsies (FNAB) will allow, in the future, to better define the neoplastic nature of some hot nodules. In personal opinion, this particular pathology must be attently searched both for its implications in the prognosis and therapeutic strategy and because it could be less rare than generally considered up to now.
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PMID:[Hyperfunctioning thyroid carcinoma. Description of a case]. 955 75


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