Vascular Endothelial Growth Factor (VEGF) and Its Receptors in Tumor-Bearing Dogs

Scheidegger, Patrick; Weiglhofer, Wolfgang; Suarez, Stéphanie; Kaser‐Hotz, Barbara; Steiner, Rudolf; Ballmer-Hofer, Kurt; Jaussi, Rolf

doi:10.1515/bc.1999.187

Cited by 62 publications

(61 citation statements)

References 15 publications

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“…Recombinant cfVEGF 164 (Canis familiaris) and VEGF-E (originating from the orf-family of pox viruses) were produced in Pichia pastoris and purified by affinity chromatography as described previously (Scheidegger et al, 1999). Recombinant hVEGF 165 was kindly provided by A Zisch (Institute of Obstetrics, University Hospital Zürich, Switzerland).…”

Section: Anti-vegf Antibodiesmentioning

confidence: 99%

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Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach

et al. 2006

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Tumour-associated macrophages, TAMs, play a pivotal role in tumour growth and metastasis by promoting tumour angiogenesis. Treatment with clodronate encapsulated in liposomes (clodrolip) efficiently depleted these phagocytic cells in the murine F9 teratocarcinoma and human A673 rhabdomyosarcoma mouse tumour models resulting in significant inhibition of tumour growth ranging from 75 to 492%, depending on therapy and schedule. Tumour inhibition was accompanied by a drastic reduction in blood vessel density in the tumour tissue. Vascular endothelial growth factor (VEGF) is one of the major inducers of tumour angiogenesis and is also required for macrophage recruitment. The strongest effects were observed with the combination therapy of clodrolip and a VEGF-neutralising antibody, whereas free clodronate was not significantly active. Immunohistologic evaluation of the tumours showed significant depletion of F4/80 þ and MOMA-1 þ and a less pronounced depletion of CD11b þ TAMs. Blood vessel staining (CD31) and quantification of the vessels as well as TAMs and tumour-associated dendritic cells (TADCs) in the A673 model showed reduction rates of 85 to 494%, even 9 days after the end of therapy. In addition, CD11c þ TADCs, which have been shown to potentially differentiate into endothelial-like cells upon stimulation by tumour released growth and differentiation factors, were similarly reduced by clodrolip or antibody treatment. These results validate clodrolip therapy in combination with angiogenesis inhibitors as a promising novel strategy for an indirect cancer therapy aimed at the haematopoietic precursor cells that stimulate tumour growth and dissemination and as a tool to study the role of macrophages and dendritic cells in tumorigenesis.

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Section: Anti-vegf Antibodiesmentioning

confidence: 99%

“…To evaluate whether SZH9 would neutralise VEGF and consequently block angiogenesis in vivo, we used the chick chorioallantois membrane assay (CAM) (Scheidegger et al, 1999). Vascular endothelial growth factor-induced angiogenesis was reproducibly inhibited by coincubation with SZH9.…”

Section: Combining Clodrolip Treatment With Vegf Neutralisation Furthmentioning

confidence: 99%

Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach

et al. 2006

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“…c This assay has been validated previously for measurement of canine VEGF, and the inter-and intra-assay variability reported by the manufacturer is less than 10%. 35,40 …”

Section: Vegf Assaymentioning

confidence: 99%

Vascular Endothelial Growth Factor Concentrations in Body Cavity Effusions in Dogs

et al. 2002

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Vascular endothelial growth factor (VEGF) has potent angiogenic, mitogenic, and vascular permeability enhancing properties specific for endothelial cells. VEGF is present in high concentrations in inflammatory and neoplastic body cavity effusions and has been implicated in the pathogenesis of neoplastic and inflammatory effusion formation. In this study, VEGF was quantitated by solid-phase enzyme-linked immunoadsorbent assay (ELISA) in samples of pericardial, pleural, and peritoneal effusions (N ϭ 38) from dogs (N ϭ 35) with neoplastic and non-neoplastic diseases. VEGF was detected in 37 of 38 effusions (median, 754; range, 18-3,669 pg/mL) and was present in much higher concentrations than in previously established normal concentrations for canine plasma (median, Ͻ1 pg/mL; range, Ͻ1-18 pg/mL) or in those previously noted in the plasma of dogs with hemangiosarcoma (HSA; median, 17 pg/mL; range, Ͻ1-67 pg/mL). In 4 dogs with HSA, the concurrent plasma VEGF concentration was much lower than in the abdominal effusion (P ϭ .029). No significant correlation was demonstrated between VEGF effusion concentration and effusion total protein content or nucleated cell count. Mean VEGF concentrations were significantly higher in pericardial (median, 3,533; range, 709-3,669 pg/mL) and pleural effusions (median, 3,144; range, 0-3,663 pg/mL) compared to peritoneal effusions (median, 288; range, 18-2,607 pg/mL; P Ͻ .05). There was no marked difference demonstrated between effusions associated with malignant and nonmalignant diseases. Further studies are necessary to elucidate the role of VEGF in body cavity effusion formation in dogs.

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“…23 The results of this study demonstrate that serum endostatin concentrations can be measured in healthy and tumor-bearing dogs by a commercially available EIA kit b and that dogs with HSA and LSA have markedly higher endostatin concentrations than do healthy dogs.…”

Section: Discussionmentioning

confidence: 66%

“…25 The cellular mechanisms responsible for the formation of endostatin are not completely understood, and all tissues capable of endostatin synthesis, storage, and release are currently unknown. 3,4,23 However, platelets and abnormal endothelium have been postulated as the major sources of endostatin and could explain the etiology of the increased endostatin concentrations in both tumor-bearing dogs and those with non-neoplastic diseases. [26][27][28] Platelets and leukocytes have been demonstrated to store and release other angiogenic factors such as VEGF.…”

Section: Discussionmentioning

confidence: 99%

Endostatin Concentrations in Healthy Dogs and Dogs with Selected Neoplasms

Rossmeisl

Bright

Tamarkin

et al. 2002

Veterinary Internal Medicne

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Endostatin prevents angiogenesis and tumor growth by inhibiting endothelial cell proliferation and migration. The purpose of this study was to determine serum endostatin concentrations in 53 healthy dogs and in 38 dogs with confirmed malignant neoplasms. Endostatin concentration was determined with a competitive enzymatic immunoassay (EIA) with rabbit polyclonal antibody generated against a recombinant canine endostatin protein. Both the presence of cancer and increasing age were associated with increased serum concentration of endostatin. Endostatin concentration in healthy dogs was 87.7 Ϯ 3.5 ng/mL. Upper and lower limits of the reference range for serum endostatin concentration in healthy dogs were 60 and 113 ng/mL. Dogs with lymphoma (LSA) and hemangiosarcoma (HSA) had endostatin concentrations of 107 Ϯ 9.3 ng/mL. In conclusion, this study demonstrates that endostatin can be quantified in dogs and that endostatin concentrations are high in dogs with HSA and LSA.Key words: Angiogenesis; Neoplasia; Vascular biology.A ngiogenesis plays an integral role in a variety of normal physiologic states and has been recognized for its role in the pathogenesis of diseases such as atherosclerosis and neoplasia. 1,2 Biologic tumor behavior is linked to the ability of neoplasms to induce endothelial cell growth and organization, with tumor growth being dependent on regulation of angiogenesis. [3][4][5][6] With in vivo and in vitro models, researchers have shown that without recruitment of a new blood supply, tumor size is limited to a few cubic millimeters because of a lack of energy substrate delivery, and expression of the metastatic phenotype is delayed or absent. 3,5 Alternatively, aggressive malignancies with high distant metastatic potential suppress anti-angiogenic factors, stimulate local production of angiogenic substances by normal host tissues, and endogenously produce active angiogenic compounds. 2,4,7 Endostatin, a carboxy-terminal fragment of collagen XVIII originally isolated from a murine hemangioendothelioma cell line, inhibits angiogenesis by preventing endothelial proliferation and migration. 3,5 Anti-neoplastic properties of endostatin have been demonstrated in vitro and in several animal models with multiple neoplastic cell lineages, and increased circulating endostatin concentrations may be associated with the development or recurrence of neoplasia in mice and humans. 3,5,[8][9][10] Hemangiosarcoma (HSA) is an aggressive malignancy primarily affecting older male, large-breed dogs. 11-17 HSA typically affects the spleen, right atrium, and skin or sub-

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Vascular Endothelial Growth Factor (VEGF) and Its Receptors in Tumor-Bearing Dogs

Cited by 62 publications

References 15 publications

Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach

Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach

Vascular Endothelial Growth Factor Concentrations in Body Cavity Effusions in Dogs

Endostatin Concentrations in Healthy Dogs and Dogs with Selected Neoplasms

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