Vascular Permeability Factor (Vascular Endothelial Growth Factor) Expression and Angiogenesis in Cervical Neoplasia

Guidi, Anthony J.; Abu‐Jawdeh, Graziella; Berse, Brygida; Jackman, Robert W.; Tognazzi, Kathi; Dvorak, Harold F.; Brown, Lawrence F.

doi:10.1093/jnci/87.16.1237

Cited by 259 publications

(156 citation statements)

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“…Third, HPV-16-encoded E6 and E7 viral oncoproteins have been implicated in the etiology of cervical cancer (Walboomers et al, 1999), as summarized in the introduction. Fourth, VEGF overexpression appears to be an important component of the angiogenic process in invasive squamous cell carcinoma of the cervix (Guidi et al, 1995;Sillman et al, 1981), similar to most other types of tumors. Increased VEGF expression and tumor vascularity have been observed in premalignant carcinoma of the cervix as well as high grade intraepithelial lesions and invasive carcinomas per se Weidner, 1994, 1997;Guidi et al, 1995;Tokumo et al, 1998) Given this information, we reasoned that HPV associated oncoproteins, particularly E6, may be responsible, at least in part, for VEGF production in various stage lesions of carcinoma of the cervix.…”

Section: Discussionmentioning

confidence: 83%

“…A similar relationship may also hold true for regulators of angiogenesis such as VEGF. With respect to HPVassociated cancers, high grade cervical dysplasia and invasive squamous cell carcinoma of the cervix are, like many other types of cancer, associated with angiogenesis (Smith-McCune and Weidner, 1994;Guidi et al, 1995;Sillman et al, 1981;Smith-McCune et al, 1997;Hove et al, 1999;Tokumo et al, 1998). However the mechanisms responsible for induction and maintenance of the angiogenic phenotype in cervical neoplasia are unknown.…”

Section: Introductionmentioning

confidence: 99%

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Oncogenes and tumor angiogenesis: the HPV-16 E6 oncoprotein activates the vascular endothelial growth factor (VEGF) gene promoter in a p53 independent manner

et al. 2000

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Oncogenes and tumor angiogenesis: the HPV-16 E6 oncoprotein activates the vascular endothelial growth factor (VEGF) gene promoter in a p53 independent manner

et al. 2000

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“…These proteins include cell adhesion molecules, proteindegrading enzymes and positive and negative angiogenesis factors (Brown and Giaccia, 1994;Dachs and Stratford, 1996). As an example, the expression of vascular endothelial growth factor, a positive angiogenesis factor known to be involved in the angiogenesis of cervical carcinoma (Guidi et al, 1995) is up-regulated significantly under hypoxic conditions both in vitro and in vivo (Plate et al, 1992;Shweiki et al, 1992;Waleh et al, 1995;Mazure et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix

Sundfør

Lyng²,

Rofstad³

1998

Br J Cancer

169

106

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Summary Some clinical studies involving several histological types of cancer have suggested that high vascular density in the primary tumour promotes metastasis. Other studies have suggested that a high incidence of metastases is associated with low oxygen tension in the primary tumour. The purpose of the study reported here was to search for correlations between incidence of metastases and oxygen tension or vascular density in the same population of patients. Thirty-eight consecutive patients with squamous cell carcinoma of the uterine cervix were included in a prospective study. Pelvic, iliac and retroperitoneal lymph node metastases were detected by magnetic resonance imaging at the time of initial diagnosis. Oxygen tension was measured polarographically using the Eppendorf P02 Histograph 6650. Vascular density was determined by histological examination of tumour biopsies. The primary tumours of the patients with metastases (n = 19) were more poorly oxygenated than those of the patients without metastases (n = 19). Thus, the fractions of the P02 readings resulting in values below 5 mmHg and 10 mmHg were significantly higher for the former group of patients than for the latter (P = 0.03 and 0.02 respectively). In contrast, the vascular density of the primary tumour was not significantly different for the two groups of patients. The present study suggests that a high incidence of metastases in squamous cell carcinoma of the uterine cervix is associated with poor oxygenation of the primary tumour and not with a high vascular density.

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“…VEGF is a dimeric glycoprotein with four spliced variants consisting of 121, 165, 189 and 206 amino acid residues expressing almost identical biological activities by binding to specific class III receptor tyrosine kinases (flt-l and KDR) (Neufeld et al, 1996;Terman and Dougher-Vermazen, 1996). Recently, Guidi et al (1995) and our group (BancherTodesca et al, 1997;Obermair et al, 1997) reported that the presence of VEGF is associated with neoplastic transformation in cervical (CIN) and in vulvar intraepithelial neoplasia (VIN), suggesting that increasing VEGF may represent an early event in the carcinogenic process.…”

mentioning

confidence: 99%

Concentration of vascular endothelial growth factor (VEGF) in the serum of patients with suspected ovarian cancer

Obermair

Tempfer²,

Hefler³

et al. 1998

Br J Cancer

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Summary As a promoter of angiogenesis, vascular endothelial growth factor (VEGF) is believed to play a pivotal role in tumour growth and metastasis. The aim of this study was to determine the value of preoperative serum VEGF levels in the early diagnosis of ovarian cancer and in the differential diagnosis of adnexal masses. We examined preoperative serum VEGF levels in healthy women (n = 131), patients with benign ovarian cysts (n = 81) and in ovarian cancer patients (n = 44) by using an ELISA (R&D Systems, Minneapolis, MN, USA). A logistic regression model was carried out to determine the influence of VEGF and CA 125 on the probability of malignancy. VEGF revealed a significant influence on the odds of presenting with malignancy vs healthy women (P = 0.001). At 363.7 pg ml-', VEGF achieved a sensitivity of 54% and a specificity of 77%. With respect to the differentiation between benign cysts and ovarian cancer, CA 125 (P < 0.0001) but not VEGF (P = 0.229) predicts the presence of malignancy in a multivariate model. In conclusion, VEGF does not appear to be a useful tool in the early diagnosis of ovarian cancer or for indicating the absence or presence of malignancy in patients with an adnexal mass.

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Vascular Permeability Factor (Vascular Endothelial Growth Factor) Expression and Angiogenesis in Cervical Neoplasia

Abstract: These observations suggest that VPF is an important angiogenic factor in cervical neoplasia.

Cited by 259 publications

References 0 publications

Oncogenes and tumor angiogenesis: the HPV-16 E6 oncoprotein activates the vascular endothelial growth factor (VEGF) gene promoter in a p53 independent manner

Oncogenes and tumor angiogenesis: the HPV-16 E6 oncoprotein activates the vascular endothelial growth factor (VEGF) gene promoter in a p53 independent manner

Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix

Concentration of vascular endothelial growth factor (VEGF) in the serum of patients with suspected ovarian cancer

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