Inactivation of PTEN is associated with increased angiogenesis and VEGF overexpression in gastric cancer

Zhou, Yong; Xiong, Yang; Wu, Xiaoting; Shi, De Bing; Fan, Wei; Zhou, Tong; Li, Yuechun; Xiong, Hanzhen

doi:10.3748/wjg.v10.i21.3225

Cited by 33 publications

(27 citation statements)

References 36 publications

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“…PTEN related angiogenesis might be attributed to its up-regulation of VEGF expression for their report. PTEN and VEGF could be used as the markers reflecting the biologic behaviors of tumor and viable targets in therapeutic approaches to inhibit angiogenesis of gastric cancers (Zhou et al, 2004). In our study we didn't find any correlation between VEGF and PTEN expression.…”

Section: Discussioncontrasting

confidence: 58%

“…OS difference was not found between PTEN, VEGF, HER2, p53 expression rates in our study. Zhou et al (2004) reported that inactivation of PTEN gene and over-expression of VEGF contribute to the neovascularization and progression of gastric cancer. PTEN related angiogenesis might be attributed to its up-regulation of VEGF expression for their report.…”

Section: Discussionmentioning

confidence: 99%

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Analysis of PTEN, VEGF, HER2 and P53 Status in Determining Colorectal Cancer Benefit from Bevacizumab Therapy

Kara

Duman²,

Kara³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Background: No factor has thus far been identified to predict the efficacy of bevacizumab therapy for colorectal cancer. We here therefore studied PTEN, VEGF, HER2 and p53 by immunohistochemistry as possible prognostic and predictive factors. Materials and Methods: A total of 34 retrospectively collected tumor samples were evaluated, all from patients receiving bevacizumab-based regimens. VEGF-A, PTEN, HER2, p53 were assessed and data was compared with clinicopathologic characteristics of patients and the bevacizumab response rate. Results: In this study, the median age of the 34 metastatic colorectal cancer patients was 55.5 (24-75), twelve (35.3%) being women and 22 (64.7%) men. PTEN, VEGF, HER2, p53 expressions were compared with bevacizumab response and other chacteristics of disease. Statistical significant differences were not found between bevacizumab response rates and different expression levels of VEGF, PTEN, HER2 and p53 (respectively p=0.256, p=0.832, p=0.189, p=0.131). However, a survival difference was noted in the VEGF expression negative group (median OS:55 months; 95%CI, 22-88 months) (p=0.01). There was no statistically significant OS difference in other groups (PTEN p=0.6, HER2 p=0.189, p53 p=0.13). Conclusions: We did not find any predictive factor for BV therapy in our study. VEGF negative expression could be an important prognostic factor in metastatic colorectal carcinoma.

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Section: Discussioncontrasting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Analysis of PTEN, VEGF, HER2 and P53 Status in Determining Colorectal Cancer Benefit from Bevacizumab Therapy

Kara

Duman²,

Kara³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…A dependency on VEGF is attributed to its ability to regulate key processes throughout the angiogenic cascade, including endothelial cell migration, proliferation and protease expression (2)(3)(4), microvascular integrin expression (5), recruitment of endothelial cell precursors (6), capillary tube formation (7), neovascular survival (8), interactions with mural cells (9), and enhanced vascular permeability (10). The production of VEGF can be disproportionately up-regulated in tumors via oncogene activation (11), loss of tumor suppressor function (12,13), or changes in oxygen or glucose status (14). Tumor capillaries induced by overexpression of VEGF are tortuous and dilated (15); an architecture that is reminiscent of immature vessels during early vascular remodeling.…”

Section: Introductionmentioning

confidence: 99%

AZD2171: A Highly Potent, Orally Bioavailable, Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase Inhibitor for the Treatment of Cancer

Wedge

Kendrew²,

Hennequin³

et al. 2005

Cancer Research

698

507

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Inhibition of vascular endothelial growth factor-A (VEGF) signaling is a promising therapeutic approach that aims to stabilize the progression of solid malignancies by abrogating tumor-induced angiogenesis. This may be accomplished by inhibiting the kinase activity of VEGF receptor-2 (KDR), which has a key role in mediating VEGF-induced responses. The novel indole-ether quinazoline AZD2171 is a highly potent (IC50 < 1 nmol/L) ATP-competitive inhibitor of recombinant KDR tyrosine kinase in vitro. Concordant with this activity, in human umbilical vein endothelial cells, AZD2171 inhibited VEGF-stimulated proliferation and KDR phosphorylation with IC50 values of 0.4 and 0.5 nmol/L, respectively. In a fibroblast/endothelial cell coculture model of vessel sprouting, AZD2171 also reduced vessel area, length, and branching at subnanomolar concentrations. Once-daily oral administration of AZD2171 ablated experimental (VEGF-induced) angiogenesis in vivo and inhibited endochondral ossification in bone or corpora luteal development in ovary; physiologic processes that are highly dependent upon neovascularization. The growth of established human tumor xenografts (colon, lung, prostate, breast, and ovary) in athymic mice was inhibited dose-dependently by AZD2171, with chronic administration of 1.5 mg per kg per day producing statistically significant inhibition in all models. A histologic analysis of Calu-6 lung tumors treated with AZD2171 revealed a reduction in microvessel density within 52 hours that became progressively greater with the duration of treatment. These changes are indicative of vascular regression within tumors. Collectively, the data obtained with AZD2171 are consistent with potent inhibition of VEGF signaling, angiogenesis, neovascular survival, and tumor growth. AZD2171 is being developed clinically as a once-daily oral therapy for the treatment of cancer.

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“…Combined with previous research results, the present study indicates that the decrease in tumor-associated VEGF by SC-560 and taxol may be a crucial mechanism in controlling angiogenesis and inducing the inhibition of overall tumor growth. Studies showed that VEGF-positive tissue was associated with a high MVD expression, whereas VEGF-negative tissue demonstrated a low expression of MVD, indicating a positive correlation between VEGF and MVD (36,37). The increase of MVD, an indirect marker of intense tumor vascularization, increases blood volume (38), and increased MVD is known to be associated with both evolution of disease and survival (39)(40)(41).…”

mentioning

confidence: 99%

Effect of the combination of a cyclooxygenase-1 selective inhibitor and taxol on proliferation, apoptosis and angiogenesis of ovarian cancer in vivo

Liu

Cai

et al. 2012

Oncology Letters

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Abstract. This study was designed to investigate the effects of a cyclooxygenase (COX)-1 inhibitor, SC-560, administered in combination with taxol, on the molecular mechanisms of antitumor efficacy in a SKOV-3 human ovarian carcinoma cell xenograft-bearing mouse model. The mice were treated with 6 mg/kg/day SC-560 by gavage twice every other day and20 mg/kg taxol by intraperitoneal injection once a week for three weeks. Microvessel density (MVD) and vascular endothelial growth factor (VEGF) mRNA levels of ovarian cancer were detected in the tumor tissues using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), respectively. The index of proliferating and apoptotic cells in the tumor tissues was determined by staining for Ki-67 and using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method, respectively. On day 7 after the end of administration, the tumor volume of mice in the combination group was reduced by 55.35% compared with that of the control mice, and the difference was statistically significant (P<0.05). In the combination group, the expression of VEGF, MVD and the cell proliferation index were inhibited significantly, while the apoptotic index was notably increased (all P<0.01, compared with the control group). Our results indicate that the molecular mechanisms of the antitumor efficacy of SC-560 combined with taxol therapy may act in part by inhibiting tumor angiogenesis, reducing cell proliferation and inducing cell apoptosis.

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Inactivation of PTEN is associated with increased angiogenesis and VEGF overexpression in gastric cancer

Cited by 33 publications

References 36 publications

Analysis of PTEN, VEGF, HER2 and P53 Status in Determining Colorectal Cancer Benefit from Bevacizumab Therapy

Analysis of PTEN, VEGF, HER2 and P53 Status in Determining Colorectal Cancer Benefit from Bevacizumab Therapy

AZD2171: A Highly Potent, Orally Bioavailable, Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase Inhibitor for the Treatment of Cancer

Effect of the combination of a cyclooxygenase-1 selective inhibitor and taxol on proliferation, apoptosis and angiogenesis of ovarian cancer in vivo

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