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

Different vascular endothelial growth factor (VEGF) gene polymorphisms have been shown to result in different VEGF gene responsiveness to various stimuli and different capacity for VEGF protein production. In the present study, we examined four VEGF gene polymorphisms in thirty-six individuals with non-small cell lung cancer (NSCLC). Gene polymorphisms were correlated with the VEGF protein expression in cancer cells and the tumor angiogenic activity. The -2578C/C, -634G/G and -1154A/A and G/A alleles in the VEGF gene were linked with low VEGF expression, while the -2578C/A, the -634 G/C and the -1154G/G alleles were linked with high VEGF expression. Tumors with -2578C/C had a significantly lower vascular density (VD) compared to the -2578C C/A. Similarly, cases with the -634G/G VEGF polymorphism had a singinificanltly lower vascular density compared to the combined C/C and G/C groups. In addition, the -1154A/A polymorphism seemed to relate with poor vaccularization but the difference did not reach significance. It is concluded that inherited VEGF sequence variations, which characterize the tumor genome itself, are strong determinants of the molecular VEGF and VEGF-downstream phenotype of NSCLC. The large variation in angiogenicity between tumors of similar histologic morphology emerges as a consequence of the 'parental' VEGF gene ability to produce VEGF.
Lung Cancer 2004 Dec
PMID:VEGF gene sequence variation defines VEGF gene expression status and angiogenic activity in non-small cell lung cancer. 1554 13

In Westernised countries, colorectal cancer (CRC) is second only to lung cancer as a cause of death from malignancy, with only 60% of patients alive at 5 years. In Stage II/III CRC, where the standard treatment is 5-fluorouracil (5-FU)/leucovorin, a recent clinical trial has shown that with the addition of oxaliplatin, fewer patients have relapsed or died at 40 months follow-up. The benefit was more pronounced in patients with Stage III than II CRC, and the addition of oxaliplatin to 5-FU/leucovorin should be considered in Stage III CRC. In metastatic CRC, where the standard treatment is 5-FU/leucovorin/irinotecan, a recent clinical trial has shown that the addition of bevacizumab, a mAb, to vascular endothelial growth factor, prolonged progression-free and overall survival. Bevacizumab is likely to become part of the standard therapy for metastatic CRC.
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PMID:Which drug combination for colorectal cancer? 1557 79

Angiogenesis is an important factor in the development of epithelial neoplasias and is useful in the study of progression and metastasis. Neoplastic cells produce angiogenic factors that overtake the antiangiogenic capacity of autoimmune cells. The vascular endothelial growth factor (VEGF) is the most important factor in the neoplastic angiogenesis. In colo-rectal carcinoma the expression of VEGF is parallel with genetic alterations and Duke's grade. In non-small cell lung carcinoma it is possible to define the angiogenic squamous dysplasia that evolves to invasive epidermoid carcinoma. In invasive gastric and lung cancer, the stromal molecules: COX 2, metalloproteinasis and adhesion molecules develop angeogenesis and their validation is important either in and therapy. In breast cancer there is a correlation between the growing of microvessels density, VEGF expression and p53 alterations, pointing to prognosis. Serological values of VEGF may also be used to monitorise the follow up of sarcomas and its reccurrence but vascular metastatic process is not yet completely understood.
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PMID:[Angiogenesis and cancer: from biopathology to therapy]. 1563 32

Angiogenesis is an essential process in the development, growth, and metastasis of malignant tumors including lung cancer. DNA sequence variations in the vascular endothelial growth factor (VEGF) gene may lead to altered VEGF production and/or activity, thereby causing interindividual differences in the susceptibility to lung cancer via their actions on the pathways of tumor angiogenesis. To test this hypothesis, we investigated the potential association between three VEGF polymorphisms (-460T > C, +405C > G, and 936C > T)/haplotypes and the risk of lung cancer in a Korean population. VEGF genotypes were determined in 432 lung cancer patients and 432 healthy controls that were frequency matched for age and sex. VEGF haplotypes were predicted using Bayesian algorithm in the phase program. Compared with the combined +405 CC and CG genotype, the +405 GG genotype found associated with a significantly decreased risk of small cell carcinoma [SCC; adjusted odds ratio (OR), 0.36; 95% confidence interval (95% CI), 0.17-0.78]. The 936 CT genotype and the combined 936 CT and TT genotype were also associated with a significantly decreased risk of SCC compared with the 936 CC genotype (adjusted OR, 0.47; 95% CI, 0.26-0.85 and adjusted OR, 0.44; 95% CI, 0.24-0.80, respectively). Haplotype CGT was associated with a significantly decreased risk of SCC (adjusted OR, 0.39; 95% CI, 0.18-0.87), whereas haplotype TCC conferred a significantly increased risk of SCC (adjusted OR, 1.63; 95% CI, 1.14-2.33). None of the VEGF polymorphisms studied significantly influenced the susceptibility to lung cancer except SCC. However, haplotypes TCT and TGT were significantly associated with the risk of overall lung cancer, respectively (adjusted OR, 0.38; 95% CI, 0.25-0.60 and adjusted OR, 3.94; 95% CI, 2.00-7.76, respectively). These effects of haplotypes TCT and TGT on lung cancer risk were observed in three major histologic types of lung cancer. These results suggest that the VEGF gene may be contribute to an inherited predisposition to lung cancer.
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PMID:Vascular endothelial growth factor gene polymorphisms and risk of primary lung cancer. 1576 31

Neoangiogenesis is required for the growth of invasive lung carcinoma, however, the role of angiogenesis in the progression of premalignant changes to carcinoma of the lung is less clear. We have evaluated vascular endothelial growth factor (VEGF) expression and microvessel densities (MVDs) in 62 bronchoscopic biopsies from normal, reactive (basal cell hyperplasia (BCH)) and dysplastic bronchial epithelium and in tissue from twenty-seven invasive lung carcinomas in an effort to demonstrate angiogenic activity in these preneoplastic lesions and determine whether it is associated with increased bronchial epithelial VEGF expression. MVDs and VEGF RNA expression measured by quantitative RT-PCR were found to be elevated in comparison to normal bronchial tissue in bronchial dysplasias and invasive lung carcinomas but not in basal cell hyperplasias. Immunohistochemical (IHC) analyses revealed that expression of VEGF arose predominantly from bronchial epithelium. ELISA analysis of lung tumor tissue showed that elevated VEGF protein expression correlated with VEGF RNA levels (r=0.59, p=0.004). Increased expression of VEGF RNA was also found in histologically normal bronchial mucosa from patients with either dysplasia at other sites or a history of heavy tobacco use suggesting a possible field effect in regard to the elaboration of VEGF. Furthermore, analysis of VEGF isoforms and VEGF receptors by semi-quantitative RT-PCR in dysplastic and invasive lesions revealed characteristic altered patterns of expression in dysplasia and early cancer as compared to normal tissue. These results indicate that angiogenesis develops early in lung carcinogenesis and is associated with overexpression of VEGF.
Lung Cancer 2005 Apr
PMID:Overexpression of vascular endothelial growth factor and its receptors in bronchial dypslasia demonstrated by quantitative RT-PCR analysis. 1577 69

Previously, we demonstrated that loss of SEMA3F, a secreted semaphorin encoded in 3p21.3, is associated with higher stages in lung cancer and primary tumor cells studied with anti-vascular endothelial growth factor (VEGF) and SEMA3F antibodies. In vitro, SEMA3F inhibits cell spreading; this activity is opposed by VEGF. These results suggest that VEGF and SEMA3F compete for binding to their common neuropilin receptor. In the present report, we investigated the attractive/repulsive effects of SEMA3F on cell migration when cells were grown in a three-dimensional system and exposed to a SEMA3F gradient. In addition, we adapted the neurobiologic stripe assay to analyze the migration of tumor cells in response to SEMA3F. In the motile breast cancer cell line C100, which expresses both neuropilin-1 (NRP1) and neuropilin-2 (NRP2) receptors, SEMA3F had a repulsive effect, which was blocked by anti-NRP2 antibody. In less motile MCF7 cells, which express only NRP1, SEMA3F inhibited cell contacts with loss of membrane-associated E-cadherin and beta-catenin without motility induction. Cell spreading and proliferation were reduced. These results support the concept that in a first step during tumorigenesis, normal tissues expressing SEMA3F would try to prevent tumor cells from spreading and attaching to the stroma for further implantation.
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PMID:Semaphorin SEMA3F has a repulsing activity on breast cancer cells and inhibits E-cadherin-mediated cell adhesion. 1580 23

To investigate the components of the prostaglandin biosynthetic pathway, the characteristics of cyclooxygenase (COX)-1, COX-2, hematopoietic prostaglandin D synthase (hPGDS), microsomal prostaglandin E synthase (mPGES), and thromboxane synthase (TXS) were examined for autopsied cases with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Autopsied patients (n=120) with lung cancer were examined, of whom 25 had SCLC and 95 had NSCLC. Immunostaining was performed for COX-1, COX-2, hPGDS, mPGES, TXS, CD34, vascular endothelial growth factor (VEGF), and basic fibroblastic growth factor (bFGF). The immunostaining scores of the prostaglandin biosynthetic pathway markers were significantly higher for adenocarcinoma than for SCLC (p<0.0001). In addition, there were significant correlations between two markers of the prostaglandin biosynthetic pathway for cases with SCLC and NSCLC. For NSCLC, the mean immunostaining scores for the prostaglandin biosynthetic pathway markers were significantly higher for cases with high count groups than low count groups for MVD, VEGF and bFGF, except COX-2 and MVD, and COX-2 and bFGF. The mean immunostaining scores for COX-1, COX-2, mPGES, and TXS were significantly higher for cases with more metastatic organs who had NSCLC. Prostaglandin biosynthetic pathway markers may act synergistically and enhance tumor angiogenesis, the expression of angiogenic factors, and metastases in patients with NSCLC.
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PMID:Characterization of the prostaglandin biosynthetic pathway in non-small cell lung cancer: a comparison with small cell lung cancer and correlation with angiogenesis, angiogenic factors and metastases. 1587 Sep 20

Endostatin (ED) is a carboxyl-terminal fragment of type XVIII collagen with a strong anti-angiogenic activity. The purpose of this study is to determine the effect of ED gene transfer into lung cancer cells on in vivo tumor growth in a murine model. The murine lung cancer cell line, Lewis Lung Carcinoma (LLC), was transfected with ED gene to express and secrete ED. After clones were selected to secrete ED, several stable transfectants with ED gene (LLC/ED) and control transfectants (LLC/Mock) were established. In vitro proliferation of these transfectants demonstrated similar growth speed. In contrast to previous reports, in vivo subcutaneous tumorignecity of LCC/ED transfectants was significantly greater than that of LLC/Mock transfectants. Immunohistochemical staining analysis demonstrated that ED gene transfer induced angiogenesis, suggesting coinduction of another gene implicated for neovascularization. As expected, LLC/ED transfectants secreted not only ED but also vascular endothelial growth factor (VEGF) to a much greater degree than LLC/mock transfectants. Interestingly, culture supernatants of LLC/ED cells enhanced in vitro proliferation of human umbilical vein endothelial cells (HUVEC) to a much greater degree than those of LLC/Mock cells. These results indicate that ED gene transfer in murine lung carcinoma cells induces VEGF secretion, resulting in enhancement of in vivo tumorigenecity in the murine model. More attention should be paid for ED gene therapy into lung cancer cells since it may influence other proteins secretion, which upregulates angiogenesis.
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PMID:Endostatin gene transfer in murine lung carcinoma cells induces vascular endothelial growth factor secretion resulting in up-regulation of in vivo tumorigenecity. 1587 83

Lung cancer is the most common cause of cancer death worldwide, with most patients dying with metastatic disease. The prognosis for the majority of patients remains poor. It is evident that advances in the treatment of this and other tumor types will require new approaches, and recent research has focused on molecular-targeted therapies. A key therapeutic strategy is inhibition of specific processes essential for tumor vascular development (a concept known to be beneficial in colorectal cancer) and a range of such antiangiogenic agents are currently in development. The most promising of these target the proangiogenic vascular endothelial growth factor (VEGF), either by preventing VEGF-receptor binding or inhibiting downstream receptor signaling. However, other more direct approaches against tumor vasculature are also in development. Since antiangiogenic agents often exert an indirect, cytostatic effect, many are being evaluated in combination with conventional chemotherapies in order to optimize the anticancer effects of both strategies. Additionally, the combination of several antiangiogenic agents is also being explored. This has become possible given the large number of agents currently available. As part of this evaluation process, the assessment of surrogate markers of target inhibition and treatment effect is ongoing in the hope of identifying reliable surrogate markers to aid the development of this new generation of anticancer agents.
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PMID:Angiogenesis and lung cancer: prognostic and therapeutic implications. 1588 12

ZD6474 selectively targets two key pathways in tumour growth by inhibiting vascular endothelial growth factor (VEGF)-dependent tumour angiogenesis and epidermal growth factor (EGF)-dependent tumour cell proliferation and survival. Phase I clinical evaluation has shown ZD6474 to be generally well tolerated, with a pharmacokinetic profile appropriate for once-daily oral dosing. Phase II evaluation of ZD6474 at doses of 100-300 mg is ongoing in a range of patient types in single and combination regimens. These include three randomised studies of patients with non-small-cell lung cancer. In one of these trials, the efficacy of ZD6474 monotherapy is being compared with that of the EGF receptor tyrosine kinase inhibitor gefitinib (Iressa) in previously treated patients. In the other two trials, the efficacy of ZD6474 in combination with certain standard chemotherapy regimens is being compared with that of standard chemotherapy alone: one with carboplatin and paclitaxel in previously untreated patients, and the second with docetaxel in patients who progressed after platinum-containing therapy. The advent of novel molecular-targeted agents such as ZD6474 has necessitated a re-evaluation of conventional cancer study design in order to optimise appraisal of this new generation of anticancer agents. The specific considerations of the ZD6474 clinical programme are discussed.
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PMID:ZD6474--clinical experience to date. 1592 53


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