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)

Three cell lines of squamous-cell carcinoma and 3 of large-cell carcinoma origin were investigated for the expression of differentiation markers and functional parameters (proliferation, morphology, cornified envelope formation, involucrin staining, transglutaminase activity, adhesiveness and migration) under normal cell culture conditions and after treatment with the tumor promoter phorbol-12-myristate-13-acetate (PMA). Although all original tumors had been described as poorly differentiated by histological grading, we found significant heterogeneity in the expression of differentiation markers in cell culture. A systematic grading of the cell lines became possible only after PMA stimulation. PMA generally increased expression of differentiation markers in cell lines of comparably low grades of differentiation, as indicated by dose-dependent inhibition of proliferation and cloning efficiency, induction of squamous markers, and decreased adhesiveness and cell motility. In contrast, cell lines of apparently higher differentiation by these criteria showed little response to PMA. The results presented show that the assessment of differentiation capacity by comparison of differentiation markers under normal cell culture and PMA-stimulated conditions in established NSCLC cell lines allows for a refined cell culture grading, which might advance the classification and characterization of such cell lines which, otherwise, appear to be very heterogeneous. It may also help to correlate cellular functions with various states of differentiation in vitro.
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PMID:Differentiation capacity of human non-small-cell lung cancer cell lines after exposure to phorbol ester. 197 42

p185neu is the protein product of the HER2/neu protooncogene. This protein has characteristics of a tyrosine kinase growth factor receptor and is postulated to be important in human carcinogenesis. To define the significance of the expression of this protein in human non-small cell lung cancer, 55 tumors from patients with squamous cell carcinoma (16), adenocarcinoma (29), or large cell carcinoma (10) of the lung were examined for p185neu using immunohistological methods. Five of 16 squamous cell carcinomas and 10 of 29 adenocarcinomas were found to overexpress p185neu relative to levels of expression seen in uninvolved bronchiolar epithelium. For the adenocarcinomas, p185neu expression was associated with older age (66.6 +/- 10.1 versus 57.5 +/- 10.8 years) (P = 0.04) and shortened survival (83.7 +/- 94.1 versus 188.5 +/- 120 weeks) (P = 0.01). In this group, using Cox's multivariate survival analysis, p185neu expression was found to be a significant determinant of survival (P = 0.04) even after accounting for the effect of tumor stage. For the squamous cell carcinomas, p185neu expression was not correlated with any of our clinicopathological parameters. Our findings indicate that non-small cell lung cancers which express p185neu do so at levels higher than that found in normal bronchiolar epithelium, and expression in adenocarcinomas of the lung is independently associated with diminished survival intervals.
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PMID:p185neu expression in human lung adenocarcinomas predicts shortened survival. 197 68

The p53 gene has been implicated as a tumor suppressor gene with mutations found in common human cancers. We examined 51 early stage, primary, resected non-small cell lung cancer specimens using an RNAase protection assay and cDNA sequencing. Mutations changing the p53 coding sequence were found in 23/51 (45%) tumor specimens, but not in the corresponding normal lung, were distributed between codons 132 to 283, and included tumors with and without 17p allele loss. Fifteen of the 23 mutations lay in the predicted binding regions for SV40 large T antigen, and 14 were located in regions highly conserved between species. G to T transversions were a common result of p53 mutations in lung cancer compared to other cancers suggesting exposure to different mutagens. In univariate and multivariate analysis the presence of p53 mutations was associated with younger age and squamous histology. However, the presence of p53 mutations was not significantly associated with tumor stage, nodal status or sex and was found in all histologic types of lung cancer. We conclude that somatic mutations in the p53 gene play an important role in the pathogenesis of early stage non-small cell lung cancer.
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PMID:Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Lung Cancer Study Group. 197 60

The mitomycins are antitumor antibiotics that are under investigation now for more than 30 years. Mitomycin C (MMC) is the best investigated subtype. It serves as a prototype for drugs with bioreductive alkylation, which is a unique feature of this class. MMC is mainly active under anaerobic circumstances. The pharmacokinetics are linear in a two-compartment model. The main toxicities of MMC are thrombocytopenia and leucocytopenia. Rare but severe side effects are a hemolytic uremic syndrome, pneumonitis and cardiac failure. MMC has a wide clinical antitumor spectrum with efficacy in various tumor types such as gastric cancer, pancreatic cancer, breast cancer, non-small cell lung cancer, cervical cancer, prostate cancer and bladder cancer. Still, the above mentioned side effects prevent a more widespread use. The most important features of the drug will be reviewed.
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PMID:Mitomycin C: mechanism of action, usefulness and limitations. 213 Oct 38

Sixteen patients with advanced non-small cell lung cancer were treated with a combination of low-dose interleukin-2 and tumor necrosis factor-alpha. Patients received a continuous 24-hour intravenous infusion of interleukin-2 at 1 X 10(6) Cetus U/m2 and a simultaneous daily intramuscular dose of tumor necrosis factor-alpha (25 to 100 micrograms/m2) for 5 consecutive days. These doses did not have antitumor activity when administered alone in previous trials. Treatment was given at 3-week intervals. Common side effects included fever, local skin reaction at the injection site of tumor necrosis factor-alpha, pancytopenia, and general malaise, all of which were reversible within 48 hours of cessation of therapy. The maximum tolerated doses with this combination were 1 X 10(6) U/m2/day of interleukin-2 and 50 micrograms/m2/day of tumor necrosis factor-alpha, with thrombocytopenia (less than 50K) being the dose-limiting toxicity. Twelve patients received two cycles or more and were evaluable for response. Measurable tumor regression occurred in four patients. An additional seven patients had radiographic stabilization of disease (median = 12 weeks) before progression. All patients had augmented lymphokine-activated killer and natural killer activity during therapy. Enhanced lysis of autologous tumor in vitro was demonstrated in four of four patients during therapy. We conclude that combination immunotherapy with low-dose interleukin-2 and tumor necrosis factor-alpha can mediate tumor regression and can be given with acceptable toxicity.
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PMID:Combination immunotherapy for non-small cell lung cancer. Results with interleukin-2 and tumor necrosis factor-alpha. 215 54

To evaluate prognostic and therapeutic significance, tumor DNA content was determined by flow cytometry in 310 paraffin-embedded tissue samples obtained surgically from 130 patients with non-small cell lung cancer. Ninety-six (76.8%) patients had DNA aneuploid patterns that were statistically higher in adenocarcinoma than in squamous cell carcinoma. A better 5-year survival rate was observed in Group A (DNA diploidy, 69.6%) than in Group B (DNA aneuploidy and DNA peridiploidy, 33.2%; P less than 0.001). The survival curves of the patients in Group B continued to decrease during the next 2.5 years. Cox's model analysis showed that both the pathologic stage and the DNA content were the significant prognostic factors for survival. However, the DNA content was an independent prognostic factor in squamous cell carcinoma, but not in adenocarcinoma. These results indicate that DNA content analysis is useful for the evaluation of clinical behavior and prognosis, and that the clinical value of the DNA content must be differentiated between squamous cell carcinoma and adenocarcinoma.
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PMID:Prognostic and therapeutic significance of the flow cytometric nuclear DNA content in non-small cell lung cancer. 215 55

Small cell lung cancer (SCLC) tumor progression can involve partial or complete conversion to a more treatment-resistant non-small cell (NSCLC) phenotype. In a cell culture model of this phenomenon, we have previously demonstrated that insertion of the viral Harvey ras gene (v-Ha-ras) into SCLC cell lines with amplification and overexpression of the c-myc gene induced many NSCLC phenotypic features. We now report that the v-Ha-ras gene can also induce morphologic, biochemical, and growth characteristics consistent with the NSCLC phenotype in an N-myc amplified SCLC cell line, NCI-H249. We show that v-Ha-ras has novel effects on these cells, abrogating an SCLC-specific growth requirement for gastrin-releasing peptide, and inducing mRNA expression of three NSCLC-associated growth factors and receptors, platelet-derived growth factor B chain, transforming growth factor-alpha (TGF-alpha), and epidermal growth factor receptor (EGF-R). TGF-alpha secretion and EGF-R also appear, consistent with the induction of an autocrine loop previously shown to be growth stimulatory for NSCLC in culture. These data suggest that N-myc and v-Ha-ras represent functional classes of genes that may complement each other in bringing about the phenotypic alterations seen during SCLC tumor progression, and suggest that such alterations might include the appearance of growth factors and receptors of potential importance for the growth of the tumor and its surrounding stroma.
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PMID:v-rasH induces non-small cell phenotype, with associated growth factors and receptors, in a small cell lung cancer cell line. 216 28

Two hundred sixteen patients with unresectable non-small cell lung carcinoma were randomly allocated to receive etoposide (120 mg/m2, days 1-3) either alone or in combination with high-dose cisplatin (60 mg/m2, days 1-2). The patients' distribution and characteristics were similar in the two treatment arms. The objective response rate for etoposide was 7% versus 25.8% for etoposide plus cisplatin (P less than 0.005). Median progression-free survival in etoposide arm was 3.5 months versus 5 months in the combination arm (P = 0.43). The median survival time for etoposide was 6 months compared with 8 months for etoposide combined with cisplatin (P = 0.87). Significantly more nausea/vomiting (P less than 0.005), serum creatinine elevation (P less than 0.005), hearing loss and/or tinnitus (P less than 0.005), peripheral neuropathy (P less than 0.005), leukopenia (P less than 0.025), and anemia (P less than 0.005) occurred in the etoposide plus cisplatin arm. No statistically significant difference was recorded between the two arms in terms of performance status changes. In conclusion the addition of high-dose cisplatin to single-agent etoposide significantly increases the chance of obtaining tumor response in advanced non-small cell lung cancer at the cost of an increased toxicity without any significant long-term impact on survival and progression-free survival.
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PMID:Etoposide versus etoposide plus high-dose cisplatin in the management of advanced non-small cell lung cancer. Results of a prospective randomized FONICAP trial. Italian Lung Cancer Task Force. 216 39

Surgical treatment and combined chemotherapy of non-small cell lung cancers during the last 10 years were analyzed. Overall 5 year survival rate of non-small cell lung cancer was 37% and those in stages I, II, IIIA and IIIB were 59%, 33%, 21% and 12%, respectively. Poor outcome in IIIA cases depended strongly on surgical respectability, however, adenocarcinoma cases depended more on the T factor and squamous cell carcinoma depended more on the N factor. IIIA cases, even though resected curatively, showed 10-20% local recurrence, indicating the importance of further improvement of the surgical procedure. In the cases with absolutely non-curative resection tumor remained in mediastinal lymph nodes or organs adjacent to the mediastinum, indicating the necessity of extended combined resection including contralateral mediastinal lymph nodes or organs adjacent to the mediastinum for better results of surgical treatment. Preoperative chemotherapy for the suppression of local recurrence and distant metastasis was significant only in very limited circumstances.
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PMID:[Present status and problems of surgical treatment of non-small cell lung cancer]. 216 40

In 678 cases of surgically resected lung cancer, morphological factors influencing prognosis were evaluated, especially in adenocarcinomas (283 cases) and squamous cell carcinomas (270 cases). In adenocarcinoma cases, sex, degree of differentiation, classification by cell type, lymphatic invasion, vascular invasion, pleural involvement, intrapulmonary metastasis, grade of scarring associated with a tumor, atypia of cells and mitotic index were significantly evaluated. The scoring of these factors will contribute to the clinician's decisions on the necessity and selection of post-adjuvant chemotherapy, especially even in Stage I. In squamous cell carcinoma cases, location of tumor, tumor size, lymphatic invasion, vascular invasion and pleural involvement were also significantly evaluated. In 160 patients treated by chemotherapy involving cisplatin, chemotherapeutic response in squamous cell carcinoma (39 cases) was more effective and survived longer these than in adenocarcinoma (107 cases) and large cell carcinoma (14 cases). In 233 non-small cell lung cancer patients treated by chemotherapy, there were 33 cases of long-term survival more than 2 years; that is, 8 cases (3.4%) disease-free and 25 cases (10.7%) alive with cancer. The group which remained disease-free for over 2 years, consisted only of patients with Stage IIIa or IIIb, and PR was achieved with chemotherapy and radiation. Among patients who lived over 2 years, many squamous cell carcinoma cases (5/6) remained disease-free. On the other hand, adenocarcinoma was less responsive to chemotherapy and almost all cases (24/27) were alive with cancer. The relationship between the effectiveness of chemotherapy and prognosis among histological subtypes was examined in small cell lung cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Histology and prognosis in lung cancer treatment]. 216 41


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