Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA from tumor samples of 54 patients with operable non-small cell lung cancer (NSCLC) was analyzed to determine whether proto-oncogene alterations could be correlated with the clinical behavior of lung cancer. Among seven proto-oncogenes tested, changes in the copy number of Ha-ras, c-myc and c-raf-1 were found in only seven tumors. Most of them were epidermoid carcinomas without lymph node involvement (N0). In spite of a localized disease with complete surgical resection, six of these patients relapsed within a mean disease-free interval (DFI) of only 6.5 months. There is a significant correlation between DNA alterations at proto-oncogene loci and clinical relapse within 12 months of surgical resection (P less than 0.025).
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PMID:DNA alterations at proto-oncogene loci and their clinical significance in operable non-small cell lung cancer. 216 42

Histological analysis remains the primary method of distinguishing between small cell (SCLC) and non-small cell lung cancer (NSCLC). This distinction has significant impact therapeutically because of their relative difference in chemoresponsiveness (J.D. Minna et al., Principles and Practice of Oncology, pp. 396-474, 1981). Yet for at least 10% of lung tumors, pathologists will disagree upon the classification (A.R. Feinstein et al., Am. Rev. Respir. Dis., 101: 671-684, 1970). Furthermore, current neuroendocrine markers lack specificity for SCLC although the presence of these markers may help predict chemosensitivity (S.L. Graziano et al., J. Clin. Oncol., 7: 1375-1376, 1989; S.B. Baylin, J. Clin. Oncol., 7: 1375-1376, 1989; C.L. Berger et al., J. Clin. Endocrinol. Metab., 53: 422-429, 1981; A.F. Gazdar et al., Cancer Res., 45: 2924-2930, 1985). In vitro growth characteristics may more accurately reflect biological properties of aggressiveness and susceptibility to chemotherapy. In this study, 3-dimensional gel-histoculture was used to retrospectively distinguish between NSCLC and SCLC. Tumor explants from 78 patients with NSCLC and 13 patients with SCLC were grown in gel-supported histocultures with an overall success rate of 92%. These 2 tumor types were distinguishable by their 3-dimensional in vitro tissue architecture. In addition, proliferation rates were measured by histological autoradiography after 4-day incorporation of [3H]dThd. The percentage of cells labeled in the most proliferatively active regions of the autoradiograms was termed the growth fraction index (A.F. Gazdar et al., Cancer Res., 45: 2924-2930, 1985; R.A. Vescio et al., Proc. Natl. Acad. Sci. U.S.A., 84: 5029-5033, 1987; R.M. Hoffman et al., Proc. Natl. Acad. Sci. U.S.A., 86: 2013-2017, 1989). The mean growth fraction index for pure small cell lung cancer was 79 +/- 10%, differing markedly from that of 35 +/- 19% for mixed small cell/large cell tumors, adenocarcinoma (38 +/- 16%), large cell undifferentiated carcinoma (40 +/- 18%), and squamous cell carcinoma (33 +/- 15%) (P less than 0.001 in each case). We therefore conclude that 3-dimensional gel-histoculture is a useful means of distinguishing pure SCLC from NSCLC, which may improve treatment decision making.
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PMID:The distinction of small cell and non-small cell lung cancer by growth in native-state histoculture. 216 89

Tauromustine (TCNU) is a newly developed nitrosourea compound. As a result of molecular modification, TCNU is more hydrophilic than BCNU and CCNU. In experimental data there was a high therapeutic index, especially in Walker 256 carcinosarcoma in rats, and in phase I trials antitumor activity was observed in NSCLC (10/33 remissions). There was also activity in melanoma, breast cancer, pleuramesotheliomas and ovarian cancer. To determine the effectiveness, duration of response and toxicity of TCNU the following phase II trial was performed. Patients received 130 mg/m2 TCNU every 35 days orally. Twenty-five patients were treated; 22 were evaluable. The female/male ratio was 18/4, 1 patient was stage III, 21 patients stage IV, the mean age was 62.3 years (range 32-70). Between 1 and 4 courses (mean 1.9) were administered. Histology was as follows: 6 squamous cell, 11 adenocarcinoma, 2 large cell and 3 polymorph cell carcinomas. No objective response (CR + PR) was observed; 6/18 patients had stable disease, 7/18 progression and 5/18 early progression. The median survival time is 4.9 months. The most severe side effect was thrombocytopenia (WHO grade 3 + 4, 4/22 patients). TCNU administered at this dose and schedule does not show substantial antitumor activity in patients with NSCLC. The fact that no objective tumor remission was observed suggests that the true response rate is less than 20% (p less than 0.05). It is improbable that TCNU has a relevant impact on the course of inoperable NSCLC.
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PMID:Chemotherapy with tauromustine in advanced non-small cell lung cancer. A trial of the Phase II Study Group of the Association for Medical Oncology of the German Cancer Society. 216 34

To assess the prognostic value of tumor proliferative activity, 89 patients with operable non-small cell lung cancer were studied. Tumor samples were obtained during surgery and cell kinetics were analyzed by the in vitro thymidine labelling index (TLI). The overall median TLI (2.9) was used to identify two subsets of patients with high and low proliferating tumors. In univariate analysis survival was significantly longer in patients with lower TLI (P = 0.047) and with stage I-II (P = 0.003) and T1-T2 tumors (P = 0.043). In multivariate analysis, stage was the most important prognostic parameter (P = 0.004). The risk of death for patients with TLI higher than 2.9 was increased (hazard ratio = 2.01, CI = 0.96-4.27).
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PMID:Thymidine labelling index as prognostic factor in resected non-small cell lung cancer. 216 78

To determine the role of lung cancer tumor imaging with monoclonal antibodies directed against high molecular weight human milk fat globule antigens, we administered i.v. 111In-KC-4G3 to 24 patients with advanced non-small cell lung cancer. One mg of 111In-KC-4G3 was mixed with 0, 9, 49, 99, or 499 mg of unlabeled KC-4G3 and infused i.v. over 1 to 5 h. The mean 111In-KC-4G3 radiochemical purity was greater than 97% and the resultant immunoreactivity averaged 62%. Successful imaging of cancer sites was accomplished in 92% of 24 patients, and 57% of 91 total lesions were visualized. Successful localization of tumor sites related to size (P less than 0.001), with 81% of lesions greater than 3.0 cm in diameter, 50% of lesions 1.5 to 3 cm, and 6% of lesions less than 1.5 cm successfully imaging, and to location (P less than 0.05), with 69% of pulmonary lesions, 80% of soft tissue lesions, and only 32% of bone metastases being visualized. Nonspecific reticulo-endothelial uptake of radioactivity was a major problem. Approximately 35% of 111In was chelated to serum transferrin by 24 and 48 h after infusion. The mean t 1/2 beta for plasma radioisotope and immunoreactive KC-4G3 was 29 and 27 h, respectively. There was no correlation between total infused antibody dose and imaging success or between total dose and effect on 111In and KC-4G3 kinetics. Circulating free KC-4 antigen was measurable in all but one patient before study. Tumor biopsy following infusion could demonstrate antibody presence but not saturable antigen binding. We conclude that (a) 111In-KC-4G3 demonstrates successful tumor localization in non-small cell lung cancers bearing generally high expression of its antigen and (b) further investigations to diminish nonspecific radioactivity for imaging and utilization of high dose radiolabeled antibody for therapeutic intent are warranted.
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PMID:Imaging of non-small cell lung cancers with a monoclonal antibody, KC-4G3, which recognizes a human milk fat globule antigen. 217 15

Studies have suggested that recombinant tumor necrosis factor-alpha (TNF-alpha) may potentiate the killing of murine tumor cells by drugs targeted at DNA topoisomerase II. We have examined the combined cytotoxic effects of the topoisomerase-targeted drug etoposide and TNF in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cell lines using clonogenic assays and a novel flow cytometry technique relying on differential uptake of fluorescein diacetate (FDA) and propidium iodide (PI) by viable and nonviable cells. Good correlation of IC50 determinations for etoposide were noted between clonogenic assays and the FDA/PI technique for both classic and variant SCLC cell lines. The effects of etoposide on the classic SCLC line H209 were potentiated by TNF with a decrease in the IC50 from 3.3 microM to 1.0 microM as determined by FDA/PI. Tumor necrosis factor alone had little effect on the growth or cloning efficiency of H209 cells. Tumor necrosis factor alone stimulated the growth and cloning of variant SCLC line N417, but the cytotoxicity of etoposide was not potentiated by TNF in N417 cells. Tumor necrosis factor alone inhibited the growth and cloning of the NSCLC line H125 but exerted a marked protective effect against higher concentrations of etoposide. It appears that the interaction of TNF with etoposide varies between cell lines and between subclasses of human lung cancer.
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PMID:Interaction of recombinant human tumor necrosis factor and etoposide in human lung cancer cell lines. 217 61

Biopsy specimens obtained from eight patients with lung cancer were tested for content of somatostatin receptors by autoradiography. Somatostatin receptors were detected in two of three patients with small cell lung cancer (SCLC) but in none of five patients with non-small cell lung cancer (NSCLC) including adenocarcinoma (two), squamous cell carcinoma (two), and bronchoalveolar carcinoma (one). In those with SCLC, specific somatostatin receptor binding was evidenced only in tumor foci and not in surrounding stroma or normal lung parenchyma. Further tissue characterization by immunoperoxidase staining with the pancytokeratin monoclonal antibody, mAB-lu-5, revealed labeling to all of the NSCLC but to none of the SCLC specimen. Selective immunoreactivity was detected in both the SCLC and the NSCLC specimen to chromogranin and neuron-specific enolase (NSE) whereas none of the specimen had detectable immunostaining to somatostatin, bombesin, serotonin, adrenocorticotropic hormone, neurofilament, calcitonin, and synaptophysin. The identification of somatostatin receptors in primary human lung cancer may have a bearing on the biology of this disease and perhaps on the clinical application of somatostatin analogues in patients with SCLC.
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PMID:Identification of somatostatin receptors in human small cell lung carcinoma. 217 45

Tumor infiltrating (TIL) and peripheral blood lymphocytes (PBL) were isolated from 18 patients with non-small cell lung cancer undergoing radical surgery. Surface marker analysis revealed that TILs and PBLs mainly consisted of CD3+ T cells and that TILs generally displayed a lower CD4/CD8 ratio. Differences were found in the expression of CD25 (IL-2 receptor) and DR (MHC class II) antigens, which were increased in TILs, and in the percentage of CD16+ natural killer (NK) cells, which was reduced in TILs as compared to PBLs. Accordingly, the NK activity of TILs was lower than that of PBLs, whereas neither TILs nor PBLs expressed spontaneous cytolytic activity against fresh autologous tumor cells, melanoma cells and the "NK-resistant" A549 lung carcinoma cell line. After 4 days of culture in medium with recombinant-interleukin-2 (rIL-2), TILs and PBLs acquired cytolytic activity against all cell targets, but TILs expressed higher levels of cytotoxicity than autologous PBLs only in 3 patients out of 16 tested. More importantly, both TILs and PBLs displayed similar levels of cytotoxic activity against autologous tumor cells. TILs and PBLs from 8 patients were also analyzed by a limiting dilution microculture system. Cloning efficiency was remarkably lower in TILs, and surface marker analysis of T cell clones confirmed that an accumulation of CD8+ lymphocytes, which displayed cytolytic activity in a lectin-dependent assay, occurred at the tumor site. The non-MHC-restricted cytolytic activity of TIL- and PBL-derived T cell clones against K562, A549, and allogeneic melanoma cells and the cytolytic activity against autologous tumor cells showed no significant differences. Only 53% of TIL clones released IL-2 in response to PHA + TPA stimulation, whereas 68% of PBL-derived clones were IL-2 producers. Moreover, most PBL- and TIL-derived clones released tumor necrosis factor alpha in response to mitogen stimulation.
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PMID:Peripheral blood and tumor infiltrating lymphocytes in non-small cell lung cancer: analysis at the population and clonal level. 217 60

Cytogenetic analysis was performed on 16 primary tumors, 2 effusions, and 3 cell lines from 21 patients with non-small cell lung cancer (NSCLC). In 20 patients specimens were obtained prior to initiating cytotoxic therapy. Extensive clonal chromosome alterations were found in all cases. The most frequent numerical changes were polysomy 7 and polysomy 20 (each seen in 12 specimens). In addition, tumor cells from another six cases exhibited partial trisomy 7, with the shortest region of overlap (SRO) at 7p11-p13. Rearrangements of chromosomes 1, 3, 6, 8, 11, 15, 17, and 19 were each observed in nine or more tumors. Breakpoints were clustered at several chromosomal sites, including 1p13, 3p13, 15p11-q11, 17p11, and 19q13. Recurrent loss involving 1p, 3p, 6q, 11p, 15p, 17p, and 19q were each seen in at least eight cases. The SRO of 3p losses was at band 3p21. Double minute chromosomes were found in three tumors. Overall, our findings indicate that even though karyotypes in newly diagnosed NSCLC are very complex, recurrent cytogenetic changes can be identified. The high incidence of loss of 17p (14 of 21 specimens) appears to be compatible with reports implicating the TP53 gene (at band 17p13) as a frequent site for genetic alteration in lung cancer. Moreover, the recurrence of loss of 3p (12 cases) and 11p (10 cases) is also consistent with recent molecular evidence. The existence of other "hot spots" for cytogenetic change, particularly those involving specific regions on chromosomes 7, 15, and 19, warrants further molecular investigation of these sites in NSCLC.
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PMID:Chromosome alterations in 21 non-small cell lung carcinomas. 217 44

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


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