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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent findings support the hypothesis that the CD34(+)-cell population in bone marrow and peripheral blood contains hematopoietic and endothelial progenitor and stem cells. In this study, we report that human AC133(+) cells from granulocyte colony-stimulating factor-mobilized peripheral blood have the capacity to differentiate into endothelial cells (ECs). When cultured in the presence of vascular endothelial growth factor (VEGF) and the novel cytokine stem cell growth factor (SCGF), AC133(+) progenitors generate both adherent and proliferating nonadherent cells. Phenotypic analysis of the cells within the adherent population reveals that the majority display endothelial features, including the expression of KDR, Tie-2, Ulex europaeus agglutinin-1, and von Willebrand factor. Electron microscopic studies of these cells show structures compatible with Weibel-Palade bodies that are found exclusively in vascular endothelium. AC133-derived nonadherent cells give rise to both hematopoietic and endothelial colonies in semisolid medium. On transfer to fresh liquid culture with VEGF and SCGF, nonadherent cells again produce an adherent and a nonadherent population. In mice with severe combined immunodeficiency, AC133-derived cells form new blood vessels in vivo when injected subcutaneously together with A549 lung cancer cells. These data indicate that the AC133(+)-cell population consists of progenitor and stem cells not only with hematopoietic potential but also with the capacity to differentiate into ECs. Whether these hematopoietic and endothelial progenitors develop from a common precursor, the hemangioblast will be studied at the single-cell level.
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PMID:In vitro differentiation of endothelial cells from AC133-positive progenitor cells. 1080 76

Defective dendritic cell (DC) function has been described previously in cancer patients and tumor-bearing mice. It can be an important factor in the escape of tumors from immune system control. However, the mechanism and clinical significance of this phenomenon remain unclear. Here, 93 patients with breast, head and neck, and lung cancer were investigated. The function of peripheral blood and tumor draining lymph node DCs was equally impaired in cancer patients, consistent with a systemic rather than a local effect of tumor on DCs. The number of DCs was dramatically reduced in the peripheral blood of cancer patients. This decrease was associated with the accumulation of cells lacking markers of mature hematopoietic cells. The presence of these immature cells was closely associated with the stage and duration of the disease. Surgical removal of tumor resulted in partial reversal of the observed effects. The presence of immature cells in the peripheral blood of cancer patients was closely associated with an increased plasma level of vascular endothelial growth factor but not interleukin 6, granulocyte macrophage colony-stimulating factor, macrophage colony-stimulating factor, interleukin 10, or transforming growth factor-beta and was decreased in lung cancer patients receiving therapy with antivascular endothelial growth factor antibodies. These data indicate that defective DC function in cancer patients is the result of decreased numbers of competent DCs and the accumulation of immature cells. This effect may have significant clinical implications.
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PMID:Clinical significance of defective dendritic cell differentiation in cancer. 1081 94

Tumour angiogenesis has been recently recognised as one of the most important prognostic factors in lung cancer. Although a variety of angiogenic factors have been identified, the angiogenesis process remains poorly understood. Bcl-2, c-erbB-2 and p53 are well-known oncogenes involved in non-small-cell lung cancer pathogenesis. A direct correlation of thymidine phosphorylase (TP) and of vascular endothelial growth factor (VEGF) with intratumoural angiogenesis has been reported. In the present study we investigated the possible regulatory role of bcl-2, c-erB-2 proteins in angiogenesis and in VEGF and TP expression in non-small-cell lung cancer. Two hundred sixteen specimens from T1,2-N0,1 staged patients treated with surgery alone were immunohistochemically examined. Bcl-2 and c-erbB-2 were significantly inversely related to each other (P = 0.04) and both were inversely associated with microvessel density (P < 0.02). High TP and VEGF reactivity was statistically related to loss of bcl-2 expression (P < 0.01). A significant co-expression of c-erbB-2 with TP was noted (P = 0.01). However, TP expression was related to high angiogenesis only in cases with absence of c-erB-2 expression (P < 0.0001). c-erbB-2 expression in poorly vascularised tumours was linked with poor outcome (P = 0.03). The present study provides strong evidence that the bcl-2 gene has a suppressive function over genes involved in both angiogenesis (VEGF and TP) and cell migration (c-erbB-2) in NSCLC. TP and c-erbB-2 proteins are significantly, and often simultaneously, expressed in bcl-2 negative cases. However, expression of the c-erbB-2 abolishes the TP-related angiogenic activity. Whether this is a result of a direct activity of the c-erbB-2 protein or a consequence of a c-erbB-2-related immune response remains to be further investigated.
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PMID:bcl-2 and c-erbB-2 proteins are involved in the regulation of VEGF and of thymidine phosphorylase angiogenic activity in non-small-cell lung cancer. 1084 53

The successful establishment of angiogenesis depends on a complex process of endothelial proliferation and organization. The angiopoietins (Ang-1 and Ang-2) and Tie2 ligand-receptor system is essential for the regulation of vascular maturation and stability during embryonic development. Together with the vascular endothelial growth factor (VEGF)-mediated pathway, they have been implicated in the control of normal physiological angiogenesis. We investigated their potential role and interaction in the development of lung cancers by comparing the expression pattern and inter-relationship of Ang-1 and 2, Tie2 and VEGF levels in 28 pairs of primary non-small cell lung cancers (NSCLC) and normal lung. Using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and in-situ hybridization (ISH), we showed that in NSCLC, there was significantly up-regulated VEGF expression by the tumour cells and an increased intensity of Ang-2 expression in the tumour vessels. The number of Ang-2-expressing vessels also correlated with the grades of tumour cell expression of VEGF. On the other hand, normal lung expressed constitutively high and correlated levels of Ang-1 and Tie2, which were significantly reduced in the carcinomas. The findings suggested a role of the Ang-1/Tie2 pathway in the maintenance of the complex vasculature in normal lung, while collaborative activities between the Ang-2 and VEGF pathways might be important in promoting tumour angiogenesis in NSCLC.
Lung Cancer 2000 Jul
PMID:The angiopoietins, tie2 and vascular endothelial growth factor are differentially expressed in the transformation of normal lung to non-small cell lung carcinomas. 1088 Aug 43

The purpose of this study is to assess the usefulness of soluble vascular endothelial growth factor (VEGF) in the effusions of patients with malignant and tuberculous diseases. Using a sandwich enzyme-linked immunoadsorbent assay, VEGF concentration was measured in malignant (n=17) and tuberculous (n=11) pleural effusions. Pleural biopsy, cytology or microbiological methods were used to make final diagnoses. Adenosine deaminase (ADA) levels in tuberculous pleural effusions were significantly higher than those in malignant pleural effusions. The median level of VEGF in patients with malignant effusions (median, 2418 pg/mL; range, 97-62103 pg/mL) was significantly higher than tuberculous effusions (median, 994 pg/mL; range, 44-3552 pg/mL). There were no significant differences in pleural VEGF levels in patients with different histological types of lung cancer. The VEGF level was not correlated with ADA, lactate dehydrogenase and total protein levels of pleural fluid. In conclusion, pleural VEGF levels in patients with malignant effusions were significantly higher than tuberculous effusions, and the measurement of pleural VEGF is helpful in discriminating between malignant and tuberculous effusions. Further studies are needed to determine the clinical value of VEGF as a tumor marker and a prognostic factor.
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PMID:Vascular endothelial growth factor in malignant and tuberculous pleural effusions. 1089 68

The interaction between the erbB tyrosine kinase receptors and their ligands plays an important role in tumor growth via the regulation of autocrine and paracrine loops. We report the effect of heregulin beta1, the ligand for erbB-3 and erbB-4 receptors, on the regulation of vascular endothelial growth factor (VEGF) expression, using a panel of breast and lung cancer cell lines with constitutive erbB-2 overexpression or engineered to stably overexpress the erbB-2 receptor. We demonstrate that heregulin beta1 induces VEGF secretion in most cancer cell lines, while no significant effect was observed in normal human mammary and bronchial primary cells. Overexpression of erbB-2 receptor results in induction of the basal level of VEGF and exposure to heregulin further enhances VEGF secretion. This is associated with increased VEGF mRNA expression. In contrast, VEGF induction is significantly decreased in a T47D cell line where erbB-2 is functionally inactivated. Conditioned media from heregulin-treated cancer cells, but not from normal cells, stimulates endothelial cell proliferation; this paracrine stimulation is inhibited by co-exposure to a specific VEGF neutralizing antibody. Furthermore, heregulin-mediated angiogenesis is observed in the in vivo CAM assay. This study reports the first evidence of VEGF regulation by heregulin in cancer cells. Oncogene (2000) 19, 3460 - 3469
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PMID:Heregulin selectively upregulates vascular endothelial growth factor secretion in cancer cells and stimulates angiogenesis. 1091 4

Angiostatin, a potent inhibitor of angiogenesis, tumor growth, and metastasis, was examined in a panel of human lung cancer cell lines with Western blot analysis and in 143 primary non-small cell lung carcinomas with immunohistochemistry. Thirty-four of 143 cases (24%) stained positively. Patients with angiostatin-positive tumors survived longer (146 weeks) than patients with angiostatin-negative tumors (77 weeks; log-rank test: P = 0.07; rank-sum test: P = 0.02). To determine whether combining stimulating and inhibiting factors might improve the prognostic capability, both angiostatin and vascular endothelial growth factor (VEGF) were analyzed together with respect to patient survival. The median survival time of patients with angiostatin-positive/VEGF-negative carcinomas was 184 weeks, whereas the median survival time of patients with angiostatin-negative/VEGF-positive tumors was only 52 weeks. The angiostatin-positive tumors exhibited an increased incidence of apoptosis and a reduced capability to be transplanted into nude mice, but these differences did not reach or were only of borderline statistical significance.
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PMID:Angiostatin expression in non-small cell lung cancer. 1095 9

Have we made any progress in the treatment of advanced non-small cell lung cancer (NSCLC) over the past 15 years? After hearing the Eastern Cooperative Oncology Group (ECOG) 1594 presented by Dr. Joan Schiller at the plenary session of the 36th Annual Meeting of ASCO, it is hard to be certain. SCHILLER: reported the results of one of the world's largest randomized trials in metastatic lung cancer comparing four platinum-based doublets. There were no differences in survival (primary endpoint) or response between these four regimens, although the cisplatin/gemcitabine arm had a superior time to progression. In her commentary on this study, Dr. Francis Shepherd concluded that progress in the treatment of metastatic lung cancer has occurred at "a snail's pace." Despite the disappointing results of ECOG 1594, there were notable trials describing new agents with novel mechanisms of action reported at this year's ASCO meeting. In small-cell lung cancer, the combination of cisplatin/ irinotecan was found to be superior to cisplatin/etoposide. For NSCLC, novel agents Iressa anti-epidermal growth factor receptor tyrosine kinase and anti-vascular endothelial growth factor monoclonal antibody appear promising.
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PMID:Lung cancer highlights. 1096 93

A reliable quantitative method for measuring gene product expression is important in investigating the relationship between growth factors and tumor biological behavior. In this study, we quantified the expression of vascular endothelial growth factor (VEGF) mRNA in 104 paired samples of lung cancer tissue and the surrounding nontumorous lung tissue using a new kinetic quantitative polymerase chain reaction (PCR) method, ie, real-time quantitative reverse transcription-PCR (RTQ RT-PCR). The samples consisted of 46 squamous cell carcinomas, 50 adenocarcinomas, and 8 undifferentiated cell carcinomas. In 17 cases, the results obtained were compared with those obtained using quantitative competitive RT-PCR (QC RT-PCR). Using RTQ RT-PCR, VEGF mRNA expression was detected and quantified in all 104 (100%) lung cancer samples and their normal counterparts. VEGF mRNA expression in the lung cancer tissue was significantly higher than in the normal counterparts (95% CI: 0.575 approximately 1.727, p < 0.001; paired t test). In 68 (65.4%) cases, VEGF mRNA expression was higher in the cancer tissue than normal tissue. VEGF mRNA expression was higher in nonsquamous cell carcinoma (p = 0.02), and higher in tumor with hilar or mediastinal lymph node metastasis (p = 0.024). QC RT-PCR was able to detect and quantify VEGF mRNA expression in 15/17 (88%) lung cancer samples and 12/17 (70.6%) normal tissue samples. The values for VEGF mRNA expression were higher in the tumor in 13 (76%) cases. Comparison of the values of the VEGF mRNA expression quantified using RTQ RT-PCR or QC RT-PCR showed a good correlation between results obtained using these two methods, both in cancer tissue (r = 0.68, p = 0.0025) and normal counterpart (r = 0.53, p = 0.027). Agreement between the results for the relative expression of VEGF mRNA expression in cancer and normal tissue obtained using these two methods was seen in 14/16 cases (88%). We conclude that RTQ RT-PCR is as accurate as QC RT-PCR and is more sensitive than QC RT-PCR in detecting and quantifying VEGF mRNA expression in lung cancer and normal tissues, and both methods reveal that the VEGF mRNA expression is higher in lung cancer tissue than in healthy lung tissue.
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PMID:Quantification of VEGF mRNA expression in non-small cell lung cancer using a real-time quantitative reverse transcription-PCR assay and a comparison with quantitative competitive reverse transcription-PCR. 1109 27

The aim of this study was to further clarify the role of the cell-associated isoform of vascular endothelial growth factor (VEGF189) on tumour growth and vascularity. Five isoforms of VEGF have been identified with different biological activities. VEGF121, VEGF145, VEGF165, VEGF189, VEGF206 are generated by alternative splicing. We used a hammerhead-type ribozyme (V189Rz) to suppress VEGF189 mRNA. The V189Rz specifically cleaved exon 6 of VEGF189 mRNA, but showed no activity against the VEGF121 or VEGF165 isoforms. The V189Rz was introduced into the human non-small cell lung cancer (NSCLC) cell line (OZ-6/VR). The expression level of VEGF189 mRNA was decreased in the OZ-6/VR cells, while VEGF121 and 165 expression was unaltered. The OZ-6/VR cells xenotransplanted into nude mice showed markedly reduced vascularisation and growth, whereas the cell line did not show any decreased growth under tissue culture conditions. The OZ-6/VR cells (1 x 10(5) cells/mouse) formed no tumours, whereas the parental OZ-6 cells formed large tumours within 8 weeks. The specific suppression of VEGF189 by the ribozyme decreased vascularity and xenotransplantability of the lung cancer cell line. Thus, the cell-associated isoform of VEGF, VEGF189, might have a key role in stromal vascularisation and the growth of NSCLC xenografts in vivo.
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PMID:Ribozyme approach to downregulate vascular endothelial growth factor (VEGF) 189 expression in non-small cell lung cancer (NSCLC). 1109 15


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