Angiogenesis in primary and metastatic epithelial ovarian carcinoma

Abulafia, Ovadia; Triest, William E.; Sherer, David M.

doi:10.1016/s0002-9378(97)70143-1

Cited by 79 publications

(52 citation statements)

References 13 publications

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“…[10][11][12][13][14][15][16] Previous studies have explored the prognostic value of microvessel counts in colorectal carcinoma, however, with contradictory results. [17][18][19][20] In the current study, one histologic section from each case was immunostained and underwent microvessel counting by two investigators who were blinded to diagnosis and the immunohistochemical markers to better standardize the result.…”

Section: Discussionmentioning

confidence: 99%

Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer

et al. 2003

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Endoglin (CD105) has been shown to be a more useful marker to identify proliferating endothelium involved in tumor angiogenesis than panendothelial markers such as CD31. We investigated endoglin and vascular endothelial growth factor expression as possible prognostic markers in colorectal cancer. Surgical specimens from 150 patients with resected colorectal carcinomas were immunostained for endoglin, CD31 and vascular endothelial growth factor. Colorectal carcinoma cases consisted of 50 cases without lymph node metastases, 50 cases with only lymph node metastases and 50 cases with liver metastases (38 cases also had positive lymph nodes). Positively stained microvessels were counted in densely vascular foci (hot spots) at Â 400 fields in each specimen. For vascular endothelial growth factor, intensity of staining was scored on a three-tiered scale. Results were correlated with other prognostic parameters. Endoglin demonstrated significantly more proliferating neoplastic microvessels than CD31 (31710 vs 1978/0.15 mm 2 field, Po0.001). Low vascular endothelial growth factor expression within tumor cells was seen in 49 (33%) and high expression in 101 cases (67%). There was a positive correlation of endoglin, CD31 counts and vascular endothelial growth factor overexpression with the presence of angiolymphatic invasion and lymph node metastases (Po0.05). Only endoglin counts correlated significantly with liver metastases and positive vascular pedicle lymph nodes (Po0.05), while vascular endothelial growth factor showed significant correlation with the depth of invasion (Po0.01). Endoglin, by staining higher numbers of the proliferating vessels in colon carcinoma, is a more specific and sensitive marker for tumor angiogenesis than the commonly used panendothelial markers. Endoglin staining also showed prognostic significance with positive correlation with angiolymphatic invasion and metastases to lymph nodes and liver.

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Section: Discussionmentioning

confidence: 99%

Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer

et al. 2003

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“…While some authors found that IMD influenced survival, others did not. The most frequently used endothelial markers were anti-FactorVIII, anti-CD31, and anti-CD34 [12][13][14][15][16][17][18][19][20][21]. Gasparini et al [22] showed a statistically significant inverse association between IMD and response to chemotherapy, while Gadducci et al [23] demonstrated a positive association between IMD and response to chemotherapy, mainly represented by a paclitaxel-platinum regimen.…”

Section: Introductionmentioning

confidence: 99%

Pretreatment serum hemoglobin level and a preliminary investigation of intratumoral microvessel density in advanced ovarian cancer

Ferrero¹,

Zola²,

Mazzola³

et al. 2004

Gynecologic Oncology

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Objective. The primary aim of this study was to evaluate the prognostic and predictive value of pretreatment serum hemoglobin level (Hb) in advanced ovarian cancer; second aim was to perform a preliminary investigation of intratumoral microvessel density (IMD).Methods. The influence on survival and response to treatment of several clinico-pathological features, including Hb, was analyzed in 72 patients with advanced ovarian cancer. IMD was assessed in tumor specimens of 25 of the 72 patients to compare three different endothelial markers: anti-FactorVIII, anti-CD31 and anti-CD34. In this subgroup of patients, a preliminary analysis of the prognostic and predictive value of IMD, and its relationship with Hb and other clinico-pathological features, was performed.Results. Hb z 12 g/dl was significantly associated with a better overall survival in univariate analysis ( P = 0.0181) and was the only independent prognostic variable in multivariate analysis ( P = 0.0160). Hb was directly related to progression-free survival ( P = 0.0240) and complete response to treatment ( P = 0.016). In the preliminary investigation of IMD, mean microvessel count did not show any significant difference among the three endothelial markers used, but anti-CD34 revealed a more consistent staining reaction. The relationship between IMD and complete response to treatment was found near to statistical significance ( P = 0.05); Hb and IMD were inversely related (r = À0.47; P = 0.045).Conclusions. Hb has a prognostic and predictive value in advanced ovarian cancer. In our preliminary study, which was performed on a limited number of patients, we found anti-CD34 to be an optimal marker for IMD determination, IMD to be a possible predictive factor of complete response to treatment, and IMD and Hb to be inversely related. D

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“…The growth and spread of malignant tumors depend on angiogenesis, 5 which also plays an important role in ovarian cancer 6 and is closely related to the prognosis. 7 SU6668 {TSU-68: (Z)-5-[(1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-ropanoic acid} is a small-molecule synthetic kinase inhibitor of the receptors Flk-1/ KDR, PDGFR␤, and FGFR1, for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), respectively.…”

mentioning

confidence: 99%

Inhibition of peritoneal dissemination of ovarian cancer by tyrosine kinase receptor inhibitor SU6668 (TSU‐68)

Machida

Saga

Takei

et al. 2004

Intl Journal of Cancer

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SU6668 (TSU-68) is a small-molecule synthetic inhibitor of the angiogenic related receptor tyrosine kinases Flk-1/KDR, PDGFR␤, and FGFR1. Using a mouse model of peritoneally disseminated ovarian cancer, we investigated whether SU6668 inhibits peritoneal dissemination and prolongs survival time. BALB/c nude mice were intraperitoneally (i.p.) inoculated with SHIN-3 (VEGF-hypersecretory) or KOC-2S (PDGF-hypersecretory) ovarian serous adenocarcinoma cells with marked peritoneal dissemination ability. From the day after i.p. inoculation of tumor cells, SU6668 was orally administered 6 times weekly at a daily dose of 100 mg/kg or 400 mg/kg. The SU6668-administered group and the vehicle-administered control group were compared for the number of tumor vascular endothelial cells, weight of peritoneally disseminated tumors, amount of ascitic fluid and survival time. As a result, these 3 parameters were significantly smaller in the SHIN-3-inoculated, SU6668-administered mice than in the control group (p ‫؍‬ 0.03, p ‫؍‬ 0.002, and p ‫؍‬ 0.02, respectively). The mean survival time was significantly longer, at 58.1 ؎ 11.2 days, in the SU6668-administered mice than that (34.5 ؎ 8.8 days) in the control group (p ‫؍‬ 0.002). Similarly, in the KOC-2S-inoculated mice, the oral administration of SU6668 significantly reduced these 3 parameters (p ‫؍‬ 0.04, p ‫؍‬ 0.04, and p ‫؍‬ 0.03, respectively), and significantly prolonged survival (16.6 ؎ 1.7 days vs. 11.0 ؎ 0.7 days, p ‫؍‬ 0.008). Thus, the oral administration of SU6668 inhibited angiogenesis and peritoneal dissemination and prolonged survival in mice with peritoneally disseminated ovarian cancer. These effects were observed with both the VEGF-and PDGF-hypersecretory cell lines. Our results suggest that molecular targeting with oral SU6668 will become a new therapeutic strategy targeting peritoneally disseminated ovarian cancer.

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Angiogenesis in primary and metastatic epithelial ovarian carcinoma

Cited by 79 publications

References 13 publications

Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer

Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer

Pretreatment serum hemoglobin level and a preliminary investigation of intratumoral microvessel density in advanced ovarian cancer

Inhibition of peritoneal dissemination of ovarian cancer by tyrosine kinase receptor inhibitor SU6668 (TSU‐68)

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