Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

Li, Chenggang; Gardy, R; Seon, Ben K.; Duff, Sarah; Abdalla, S A; Renehan, Andrew G; O’Dwyer, Sarah T; Haboubi, Najib; Kumar, Shant

doi:10.1038/sj.bjc.6600874

Cited by 110 publications

(85 citation statements)

References 27 publications

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“…Tomisaki et al (1996), in assessing an association correlation between MVD and liver metastasis, found a mean MVD of 64 in colorectal cancer patients with hepatic metastasis compared with a mean MVD of 52 in patients without metastasis (P ¼ 0.001). In addition, the relationship in colorectal cancer between MVD and prognosis has also been described in most studies indicating a positive correlation between high MVD and poor outcome (Vermeulen et al, 1999;Li et al, 2003). We have shown a direct relationship between increasing MVD and cancer-specific survival.…”

Section: Discussionmentioning

confidence: 49%

Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis

et al. 2009

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The hypoxia-mediated response of tumours is a major determining factor in growth and metastasis. Understanding tumour biology under hypoxic conditions is crucial for the development of antiangiogenic therapy. Using one of the largest cohorts of rectal adenocarcinomas to date, this study investigated hypoxia-inducible factor-1a (HIF-1a) and HIF-2a protein expression in relation to rectal cancer recurrence and cancer-specific survival. Patients (n ¼ 90) who had undergone surgery for rectal adenocarcinoma, with no prior neoadjuvant therapy or metastatic disease, and for whom adequate follow-up data were available were selected. Microvessel density (MVD), HIF-1a and HIF-2a expressions were assessed immunohistologically with the CD34 antibody for vessel identification and the NB100-131B and NB100-132D3 antibodies for HIF-1a and HIF-2a, respectively. In a multifactorial analysis, results were correlated with tumour stage, recurrence rate and long-term survival. Microvessel density was higher across T and N stages (Po0.001) and associated with poor survival (hazard ratio (HR) ¼ 8.7, Po0.005) and decreased disease-free survival (HR ¼ 4.7, Po0.005). hypoxia-inducible factor-1a and -2a were expressed in 450% of rectal cancers (HIF-1a, 54%, 48/90; HIF-2a, 64%, 58/90). HIF-1a positivity was associated with both TNM stage (Po0.05) and vascular invasion (Po0.005). In contrast, no associations were shown between HIF-2a expression and any pathological features, and HIF-1a positivity had no effect on outcome. The study showed an independent association between HIF-1a expression and advanced TNM stage with poor outcome. Our results indicate that HIF-1a, but not HIF-2a, might be used as a marker of prognosis, in addition to methods currently used, to enhance patient management.

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Section: Discussionmentioning

confidence: 49%

Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis

et al. 2009

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“…The explanation of endoglin decrease after the operation in colorectal cancer patients might be at least in part due to pro-inflammatory cytokines, such as tumour necrosis factor α action. TNF-α has been reported to downregulate endoglin at post-transcriptional level [15]. Li et al [15] did not find significant difference between pre-and postoperative samples from 14 colorectal cancer patients, suggesting that postoperative angiogenesis during the process of wound healing is likely to overshadow a lowered endoglin level following removal of the tumour.…”

Section: Discussionmentioning

confidence: 99%

“…Elevated serum endoglin was associated with distant metastases not only in breast, but also in colorectal cancer and in other solid tumors [19]. Also Li et al [15] using an indirect sandwich ELISA described a correlation between plasma endoglin and Dukes' stages.…”

Section: Discussionmentioning

confidence: 99%

“…Many reports indicate that endoglin assessed immunohistochemically in colorectal cancer correlates not only with tumor microvessel density, but also with survival [7,15]. It has been also reported as a valuable parameter predicting patients having an increased risk of developing metastatic disease [16].…”

Section: Introductionmentioning

confidence: 99%

“…Soluble endoglin was shown to be increased in many tumors including: myeloid malignancies and breast cancer [18]. Two studies also documented elevated levels of circulating endoglin in colorectal cancer patients [15,19]. Both used local immunoassays for its detection.…”

Section: Introductionmentioning

confidence: 99%

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Combined perioperative plasma endoglin and VEGF-A assessment in colorectal cancer patients.

Myśliwiec¹,

Pawlak²,

Kukliński³

et al. 2009

Folia Histochem Cytobiol.

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Abstract:Colorectal cancer growth and spread is absolutely dependent on angiogenesis with vascular endothelial growth factor (VEGF) being the most important cytokine involved in the process. Endoglin, a membrane co-receptor for TGF-β, has recently emerged as a sensitive index of cancer stage. There is now sufficient evidence indicating that microvessel density assessed by endoglin-immunostaining correlates with stage of colorectal cancer and patient survival. An association of a soluble form of endoglin with lymph node and distant metastases has recently been reported in two studies. Both of them used local elaborated immunoassays for endoglin assessment. The aim of our study was to determine the efficacy of plasma endoglin, assessed using a commercial kit, as a marker of tumor spread and distant metastases in colorectal cancer patients. We studied 48 colorectal cancer patients, compared with 22 healthy subjects, using ELISA. We observed that colorectal cancer patients had increased plasma VEGF-A, but not endoglin levels. However, we found an association of plasma endoglin with the stage of malignancy. Endoglin levels were increased in metastasis-positive patients when compared to both metastasis-negative patients and healthy volunteers. Plasma endoglin correlated with VEGF-A, CEA and CA19.9. Endoglin assessment in plasma does not seem useful as a maker of colorectal cancer. Our observations indicate however that it might be helpful in selecting patients with metastatic disease.

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Perfusion of ⁹⁹Tc^m‐labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target

Costello¹,

Li²,

Duff³

et al. 2004

Intl Journal of Cancer

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There is strong published and unpublished evidence that our CD105 Mab E9, which is highly reactive with angiogenic endothelial cells, could be a useful reagent to target the vasculature of solid tumors in man. Since Mab E9 does not cross-react with animal tissues, we undertook here to evaluate its localization using human kidney as an ex vivo model. Perfusion was performed through the renal artery of 99 Tc mlabeled purified CD105 Mab in freshly excised kidneys from 7 patients with renal carcinoma. In all 7 cases, immunoscintigraphs showed the presence of well-defined radioactive hot spots, which matched the positions of the tumors as identified by presurgery MRI scans and subsequent histopathologic examination. Importantly, in one instance, where a presurgery MRI scan had identified only one tumor, immunoscintigraphs showed 2 distinct hot spots of radioactivity. The pathology report confirmed that the additional hot spot corresponded to a small secondary well-vascularized tumor. Renal cell carcinoma (RCC) is the most common cancer of the kidney. Approximately one-third of patients already have distant metastases at diagnosis and the prognosis of these patients is poor (e.g., 5-year survival for stage IV is almost zero). 1 Conventional prognostic markers such as tumor size, staging and grading have proved insufficient. There is thus an urgent need to develop alternative prognostic markers and more effective treatment modalities. Angiogenesis, the formation of new blood vessels, is essential for tumor growth and metastasis and intratumor microvessel density has emerged as an independent prognostic marker for some solid tumors. 2,3 The absolute dependence of tumors on angiogenesis makes endothelial cells (ECs) an attractive therapeutic target for controlling both primary tumor growth and metastasis. 2,4 -17 This approach has several advantages over conventional treatments. 4,15 First, unlike the cancer cells it supports, tumor endothelium is not transformed and not subject to phenotypic variations. It is therefore unlikely that antiangiogenic strategies will suffer from the problem of secondarily acquired drug resistance, which bedevils existing therapies. Second, antiangiogenic targeting therapy may be able to overcome the problem of tumor heterogeneity, which is a major problem in tumor cell targeted therapy. Third, the physical barriers to penetration into solid tumors could be circumvented by targeting the tumor vasculature, which is more accessible than the neoplastic cells in a tumor mass. Fourth, many thousands of dependent tumor cells will die of nutrient deprivation if a capillary or segment of a microvessel fails. It is estimated that a small microvessel supports approximately 3,000 tumor cells. Fifth, a single agent developed for antiangiogenic targeting could be applied to most or all types of solid tumor and other angiogenesisdependent diseases.In order to develop an antiangiogenic therapy, it is imperative to have appropriate reagents that selectively destroy the tumor-associated vasculature without ...

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Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

Cited by 110 publications

References 27 publications

Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis

Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis

Combined perioperative plasma endoglin and VEGF-A assessment in colorectal cancer patients.

Perfusion of ⁹⁹Tc^m‐labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target

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Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

Cited by 110 publications

References 27 publications

Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis

Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis

Combined perioperative plasma endoglin and VEGF-A assessment in colorectal cancer patients.

Perfusion of 99Tcm‐labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target

Contact Info

Product

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Perfusion of ⁹⁹Tc^m‐labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target