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

We have found growth-promoting activity for vascular endothelial cells in the conditioned medium of a human lung cancer cell line, T3M-11. Purification and characterization of the growth-promoting activity have been carried out using ammonium sulfate precipitation and gel-exclusion chromatography. The activity migrated as a single peak just after ribonuclease. It did not bind to a heparin affinity column. These results suggest that the activity is not a heparin-binding growth factor (including fibroblast growth factors) or a vascular endothelial growth factor. To identify the molecule exhibiting the growth-promoting activity, a cDNA encoding the growth factor was isolated through functional expression cloning in COS-1 cells from a cDNA library prepared from T3M-11 cells. The nucleotide sequence encoded by the cDNA proved to be identical with that of insulin-like growth factor II.
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PMID:Isolation of a cDNA for a growth factor of vascular endothelial cells from human lung cancer cells: its identity with insulin-like growth factor II. 773 Jan 45

The relationship between vascular endothelial growth factor (VEGF) and lymph node metastasis was studied in 90 cases of primary lung cancer without distant metastasis. As a result of quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis, the VEGF121 mRNA expression levels in lung cancer tissues with nodal metastasis (n = 35) were higher than in those without nodal metastasis (n = 55). However, no significant difference could be found in VEGF121 mRNA expression levels as stratified by tumour size (T1N0M0 vs T2N0M0). Simultaneously, ten lymph nodes (four node positive and six node negative) together with the corresponding primary lung tumours and adjacent normal lung tissue, were studied for VEGF expression. The VEGF mRNA expression in metastatic lymph nodes was intense in three out of the four cases examined. Further, while VEGF expression levels in metastatic lymph nodes were conspicuously higher than those for the primary site, all its expression levels in non-metastatic nodes were inferior to those of the primary tumours. Except for macrophages, the VEGF antigen was identified mainly in the cytoplasm of metastatic cancer cells and the endothelial cells of blood or lymphatic vessels in lymph nodes. Although the detailed mechanisms and the significance of strong VEGF expressions in metastatic lymph nodes are still unknown, these data are consistent with a model whereby VEGF increases the opportunity for nodal metastasis through neoblood and lymphatic vessels.
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PMID:Vascular endothelial growth factor and lymph node metastasis in primary lung cancer. 968 8

We investigated the inhibitory effect of clarithromycin, a 14-membered ring macrolide antibiotic, on tumor-induced angiogenesis in vivo using a mouse dorsal air sac model. The inhibitory effect of clarithromycin was dose-dependent, and 100 mg/kg of clarithromycin administered intraperitoneally twice a day reduced the area of dense capillary network to about 30% that of the control. However, in concentrations up to 50 microM clarithromycin had no effect on lung cancer cells and human vascular endothelial cell growth, endothelial cell migration, or lung cancer cell production of the angiogenesis-inducing factors interleukin-8 and vascular endothelial growth factor. Clarithromycin in concentrations greater than 10 microM inhibited endothelial cell tube formation on Matrigel in a dose-dependent manner. These data suggest clarithromycin is a potent inhibitor of tumor-induced angiogenesis that exerts its effect by inhibiting endothelial cell tube formation, and may be a possible candidate for therapeutic application.
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PMID:Clarithromycin is a potent inhibitor of tumor-induced angiogenesis. 944 Jan 37

Thrombin-catalyzed, cross-linked fibrin (XLF) formation is a characteristic histopathological finding in many human and experimental tumors and is thought to be of importance in the local host defense response. Although the pathogenesis of tumor-associated fibrin deposition is not entirely clear, several tumor procoagulants have been described as likely primary stimuli for the generation of thrombin (and XLF) in the tumor microenvironment (TME). In a previous study of a variety of human tumors we have shown that tissue factor (TF) is the major procoagulant. However, the relative contribution to fibrin deposition in the TME of tumor cell TF and host cell TF (eg, macrophage-derived) was not established. In addition, recent evidence has implicated TF in the regulation of the synthesis of the pro-angiogenic factor vascular endothelial growth factor (VEGF) by tumor cells. In the current study we used in situ techniques to determine the cellular localization of XLF, TF, VEGF, and an alternative tumor procoagulant, so-called cancer procoagulant (CP), a cysteine protease that activates clotting factor X. In lung cancer we have found XLF localized predominantly to the surface of tumor-associated macrophages, as well as to some endothelial cells and perivascular fibroblasts in the stromal area of the tumors co-distributed with TF at the interface of the tumor and host cells. Cancer pro-coagulant was localized to tumor cells in several cases but not in conjunction with the deposition of XLF. TF and VEGF were co-localized in both lung cancer and breast cancer cells by in situ hybridization and immunohistochemical staining. Furthermore, a strong relationship was found between the synthesis of TF and VEGF levels in human breast cancer cell lines (r2 = 0.84; P < 0.0001). Taken together, these data are consistent with a highly complex interaction between tumor cells, macrophages, and endothelial cells in the TME leading to fibrin formation and tumor angiogenesis.
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PMID:Activation of coagulation and angiogenesis in cancer: immunohistochemical localization in situ of clotting proteins and vascular endothelial growth factor in human cancer. 946 66

Tumor growth and metastasis are angiogenesis-dependent processes initiated and regulated by a number of cytokines. Vascular endothelial growth factor (VEGF) is a potent angiogenic protein with a selective mitogenic effect on vascular endothelial cells, known to be involved in physiological (embryogenesis) and pathophysiological (rheumatoid arthritis, tumor) angiogenesis. An increased expression of matrix metalloproteinase type IV collagenase has been reported in invading endothelial cells in vitro and in malignant cells, degrading structures of the basement membranes in various human malignancies. In the present study we investigated the expression of the genes for type IV collagenase and vascular endothelial growth factor (VEGF) in 40 cases of primary non-small-cell lung cancer (NSCLC). Specimens were immunostained by an antibody directed against VEGF and mRNA transcripts of VEGF and type IV collagenase were localized by non-radioactive in situ hybridization. VEGF mRNA was detected in 33 neoplasms, while in 23 cases transcripts of the type IV collagenase gene were visualized by digoxigenin-labeled cDNA probes. Transcripts of both mRNAs were detected in malignant cells. Furthermore, anti-VEGF immunostaining was present in newly formed microvessels close to the atypical cells, and mRNA of type IV collagenase was present in stromal cells adjacent to the tumor. A statistically significant correlation was found between the expression of type IV collagenase and VEGF (P = 0.0061). These data suggest a double role for type IV collagenase in the metastatic process of NSCLC: (1) facilitating the invasion of tumor cells by the proteolytic cleavage of the basement membrane and (2) similarly supporting the endothelial cell invasion essential for tumor angiogenesis. Furthermore, our findings sustain the hypothesis that metastatic spread and angiogenesis are associated with a clonal expansion of highly angiogenic and invasive tumor cell clones.
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PMID:Expression of type IV collagenase correlates with the expression of vascular endothelial growth factor in primary non-small cell lung cancer. 962 Feb 25

The expression of mRNAs for vascular endothelial growth factor (VEGF) was examined in 42 cases of primary lung cancer tissues (18 adenocarcinomas, 18 squamous cell carcinomas, 2 large cell carcinomas, 3 small cell carcinomas, and 1 adenoid cystic carcinoma) and 4 human lung cancer cell lines. As seen by reverse transcription-PCR analysis, VEGF mRNAs were expressed predominantly as transcripts for the secretory forms of VEGF (VEGF121 and VEGF165), both in resected lung cancer tissues and in human lung cancer cell lines. The positive ratios of VEGF mRNA according to pathological type were 66.7% (12 of 18) in adenocarcinoma, 72.2% (13 of 18) in squamous cell carcinoma, 100% (2 of 2) in large cell carcinoma, and 67% (2 of 3) in small cell carcinoma. The relative antigen levels of VEGF detected by immunohistochemical examination almost coincided with the relative VEGF mRNA expression levels. Also, we examined the expression of basic fibroblast growth factor mRNA in the same tumor specimens. However, no significant correlation was found between the VEGF and basic fibroblast growth factor mRNA expression levels. We assessed the relationship between the VEGF121 mRNA expression level and the survival period in patients (n = 17) who underwent a curative operation at stage I of the disease. The median survival of the VEGF high-expression group was 8 months, and that of the VEGF low-expression group was 151 months. The 3- and 5-year survival rates of the high-expression group (n = 6) were 50.0% and 16.7%, respectively. On the other hand, those of the low expression group (n = 11) were 90.9% and 77.9%, respectively. The difference in survival between the two groups was significant (P < 0.05). Among eight cases of long-term survival beyond 5 years, seven cases had low or no VEGF121 mRNA expression. In contrast, among 18 cases with VEGF121 mRNA overexpression, 17 cases died due to recurrence. As a marker of tumor angiogenesis, the VEGF121 mRNA expression level may be a significant prognostic indicator of lung cancers in early stages.
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PMID:Significance of vascular endothelial growth factor messenger RNA expression in primary lung cancer. 981 15

We examined the effects of roxithromycin, a 14-membered ring macrolide antibiotic, on tumor angiogenesis using a mouse dorsal air sac model. The inhibitory effect of roxithromycin was dose-dependent and 100 mg/kg of roxithromycin administered intraperitoneally twice a day reduced the dense capillary network area to about 20% of the control. However, at concentrations of up to 50 microM, roxithromycin had no effect on lung cancer cells and human vascular endothelial cell growth and lung cancer cell production of the angiogenesis-inducing factors interleukin-8 and vascular endothelial growth factor. Roxithromycin at concentrations greater than 20 microM inhibited endothelial cell migration and tube formation.
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PMID:Inhibition of tumor angiogenesis by roxithromycin, a 14-membered ring macrolide antibiotic. 985 Dec 45

The vascular endothelial growth factor (VEGF) is known to be one of the most important angiogenic factors under both physiological and pathological conditions. The VEGF overexpression by a wide spectrum of neoplastic diseases has suggested an important role of this cytokine in tumor-neovascularization. A method is described for quantification by reverse transcription-polymerase chain reaction (RT-PCR) of VEGF mRNA in non-small cell lung cancer tissues (NSCLC). The method entails addition to the sample of competitor DNA molecules that share the same primer recognition sites as the amplified target, but which can be easily distinguished by gel electrophoresis because of their different lengths (competitive PCR). We analyzed the VEGF mRNA expression level in 34 cases of lung tumor tissues compared to the respective adjacent normal tissues. In 4 out of 34 (11.7%) analyzed couples there was no VEGF mRNA expression, in 8 out of 34 (23.5%) only normal parenchymal tissue was positive for VEGF mRNA expression; in the remaining 22 cases (64. 7%) both normal and tumor tissues showed PCR products for VEGF. In 17 out of these 22 couples (77.2%) a higher number of VEGF mRNA molecules were present in tumor specimens than in the normal counterpart. According to these results, the competitive PCR-method seems to provide a useful tool for the quantitate VEGF expression in order to identify its role in the development of lung cancer.
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PMID:Quantitation by competitive PCR assay of vascular endothelial growth factor in non-small cell lung carcinomas. 986 24

Angiogenesis in tumors is influenced by several factors which in turn are associated with chemoresistance or radioresistance. Moreover, the tumors of smokers are known to be relatively resistant to chemotherapy. This investigation attempts to determine whether or not a relationship exists between cigarette smoking and angiogenesis in lung cancer. Tumor samples from 14 non-smokers and 14 heavy cigarette smokers were selected for this study. The populations were matched for age, sex and tumor stage. Resistance to doxorubicin, microvessel density, the expression of vascular endothelial growth factor (VEGF) and thrombospondin (TSP) were analyzed in both populations. Tumors of smokers were more frequently resistant to doxorubicin in vitro, had lower vessel counts and a reduced expression of VEGF compared to tumors of nonsmokers. In contrast, TSP was significantly increased in the tumors of smokers. These data show that angiogenesis in lung tumors is linked to a patient's smoking habits.
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PMID:Angiogenesis and cigarette smoking in squamous cell lung carcinomas: an immunohistochemical study of 28 cases. 1022 63

In order to explore whether apoptosis is associated with angiogenesis in lung cancer, immunohistochemistry was employed to determine the pro-apoptotic factors Fas ligand (FasL) and caspase-3 (Cas-3) in 70 squamous cell lung carcinomas. Furthermore, the vascular endothelial growth factor (VEGF) and the microvessel density (MVD) were analyzed. The comparison between MVD and the pro-apoptotic factors demonstrated that the apoptotic factors are inversely related to MVD (Cas-3: p = 0.011, FasL: not significant). In order to confirm this result, FasL and Cas-3 were also compared with the expression of VEGF. Again, an inverse correlation between VEGF and the pro-apoptotic factors was found (Cas-3: p = 0.019, FasL: p = 0.008). The inverse correlation between angiogenesis and apoptosis may be explained by the activation of pro-apoptotic and anti-angiogenic factors caused by hypoxia.
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PMID:Inverse correlation between apoptotic (Fas ligand, caspase-3) and angiogenic factors (VEGF, microvessel density) in squamous cell lung carcinomas. 1047 99


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