Activated Vegfr2/kdr Pathway In Tumour Cells And Tumour Associated Vessels Of Colorectal Cancer

Giatromanolaki, Alexandra; Koukourakis, Michael I.; Sivridis, Efthimios; Chlouverakis, Gregorios; Vourvouhaki, Ekaterini; Turley, Helen; Harris, Adrian L.; Gatter, Kevin C.

doi:10.1111/j.1365-2362.2007.01866.x

Cited by 77 publications

(65 citation statements)

References 37 publications

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“…IGF-1R, which is expressed at low levels in normal hepatocytes, is also overexpressed in human HCC tissues, whereas the expression levels of IGFBP-3, a negative regulator of the IGF/IGF-1R axis, are decreased in human HCC samples and this is associated with poor survival of HCC patients [31][32][33]. In addition, an overexpression and activation of the VEGF/VEGFR axis is observed in both human CRC and HCC, and this has also been shown to correlate with poor prognosis for these malignancies [34][35][36][37]. Therefore, targeting these RTKs and their downstream pathways may be a potentially effective strategy for the prevention and, in certain cases, treatment of some types of human malignancies, including CRC and HCC [9][10][11].…”

Section: Abnormalities In Rtks and Colorectal And Liver Cancersmentioning

confidence: 99%

Cancer chemoprevention with green tea catechins by targeting receptor tyrosine kinases

Shimizu

Adachi

Masuda

et al. 2011

Molecular Nutrition Food Res

106

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Recent studies indicate that receptor tyrosine kinases (RTKs), which play important roles in cell proliferation, are one of the possible targets of green tea catechins (GTCs) in cancer cell growth inhibition. (-)-Epigallocatechin-3-gallate (EGCG), the major catechin in green tea, inhibits cell proliferation and induces apoptosis in various types of cancer cells, including colorectal cancer and hepatocellular carcinoma cells, by blocking the activation of the epidermal growth factor receptor (EGFR) family of RTKs. EGCG inhibits the activation of insulin-like growth factor-1 receptor (IGF-1R) and VEGFR2, the other members of the RTK family, and this effect is also associated with the anticancer and chemopreventive properties of this agent. EGCG suppresses the activation of EGFR in part by altering membrane lipid organization and causing the subsequent inhibition of the dimerization and activation of this receptor. Preliminary trials have shown that GTCs successfully prevent the development and progression of precancerous lesions, such as colorectal adenomas, without causing severe adverse effects. The present report reviews evidence indicating that GTCs exert anticancer and chemopreventive effects by inhibiting the activation of specific RTKs, especially EGFR, IGF-1R, and VEGFR2, and concludes that targeting RTKs and their related signaling pathways by using tea catechins could be a promising strategy for the prevention of human cancers.

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Section: Abnormalities In Rtks and Colorectal And Liver Cancersmentioning

confidence: 99%

Cancer chemoprevention with green tea catechins by targeting receptor tyrosine kinases

Shimizu

Adachi

Masuda

et al. 2011

Molecular Nutrition Food Res

106

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“…Importantly, Guo et al found that KDR could regulate tumor angiogenesis directly [29]. It is reported that overexpression of KDR had close-knit association with many kinds of cancers, such as lung cancer, breast cancer, ovarian cancer, colon cancer, and uterus cancer [29][30][31]. Subsequently, Knizetova et al found that KDR played the role as intracellular regulator mainly via some important signaling cascades, such as the pathways of PLC/ PKC, c-Raf/MAPK, and P13 K/Akt [32].…”

Section: Introductionmentioning

confidence: 97%

Genetic Variations of Kinase Inserts Domain Receptor (KDR) Gene Are Associated with the Risk of Astrocytomas

Gao

et al. 2015

Mol Neurobiol

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Astrocytomas is one of the most common central nervous system (CNS) tumors with high mortality rate. Kinase insert domain receptor (KDR) is involved in the regulation of tumor angiogenesis, migration, and vascular permeability. The aim of the study was to explore the relationship between KDR polymorphisms and risk of astrocytomas. Blood samples were collected from 157 astrocytomas patients and 160 healthy controls. Three tag-SNPs (rs2071559C/T, rs2305948T/C, and rs1870377A/T) were identified from the International HapMap Project Databases and genotyped using the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We evaluated the astrocytomas risk caused by individual SNPs and haplotype using odds ratios (ORs) and their 95 % confidence intervals (CIs). In the overall individual SNP analysis, the C allele of rs2071559 was correlated with an increased risk of astrocytomas. However, individuals with mutant allele A and genotype TA + AA of rs1870377 showed a protective effect against astrocytomas. Subgroup analysis based on WHO tumor grade revealed that the C allele of rs2071559 had more influence with the risk of astrocytomas in the grade III-IV (OR = 1.91) subgroup than the grade I-II (OR = 1.47) group. Genotype TT of rs2305948 was found to be significantly associated with susceptibility of astrocytomas only in the grade III-IV subgroup. The protective effect of rs1870377 did not reveal significant difference between the grade III-IV and grade I-II subgroups. Meanwhile, stratified analysis demonstrated that mutation of rs2071559 and rs2305948 could elevate the risk of astrocytomas more significantly in the subgroup of smokers than the nonsmokers. Interestingly, the protective effect of rs1870377 was more obvious in the nonsmokers than the smokers. Additionally, haplotype-specific analysis showed that haplotype CCT and CTT were related with an increased risk of astrocytomas. We found that individual with variants of rs2071559*C and rs2305948*T might significantly elevate the risk of astrocytomas, while mutants of rs1870377*A was associated with the decreased risk of astrocytomas. Further studies about ethnically diverse populations with larger sample size should be performed to confirm the correlation between KDR gene polymorphisms and risk of astrocytomas.

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“…in the literature, we found no studies measuring VeGFr-1 or VeGFr-2 protein concentrations in crc and normal colorectal tissue using the quantitative eliSa technique. a few studies using semi-quantitative techniques, such as immunohistochemistry, found indications of higher VeGFr-2 protein expression in crc compared to normal colorectal tissue (18,19), but a direct comparison with our study is of course not possible due to the substantial differences in the techniques employed.…”

Section: Discussionmentioning

confidence: 39%

Quantitative analysis of vascular endothelial growth factor receptors 1 and 2 in colorectal cancer

Hansen¹

2009

Mol Med Rep

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Activated Vegfr2/kdr Pathway In Tumour Cells And Tumour Associated Vessels Of Colorectal Cancer

Cited by 77 publications

References 37 publications

Cancer chemoprevention with green tea catechins by targeting receptor tyrosine kinases

Cancer chemoprevention with green tea catechins by targeting receptor tyrosine kinases

Genetic Variations of Kinase Inserts Domain Receptor (KDR) Gene Are Associated with the Risk of Astrocytomas

Quantitative analysis of vascular endothelial growth factor receptors 1 and 2 in colorectal cancer

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