Anti-angiogenic therapy, a new player in the field of sarcoma treatment

Versleijen-Jonkers, Yvonne M.H.; Vlenterie, Myrella; Luijtgaarden, Addy C.M. van de; Graaf, Winette T.A. van der

doi:10.1016/j.critrevonc.2014.02.001

Cited by 30 publications

(26 citation statements)

References 117 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The good results obtained with combinations of anti-angiogenesis and conventional cancer therapy in clinical and preclinical studies [11,26,27] support the idea that such a combination might be more effective to eradicate vasculogenic tube formation. The model we present could be used to provide further information on angiogenesis in Os [11,28,29].…”

Section: Discussionmentioning

confidence: 98%

The early stages of tumor angiogenesis in human osteosarcoma: a nude mice xenotransplant model

et al. 2015

View full text Add to dashboard Cite

Osteosarcoma (Os) is the most common malignant bone tumor in childhood and not rare in adults. In recent years, much research has focused on the role of angiogenesis in tumor development, growth, invasion, and metastasis. The aims of this study were to characterize neovascularization established between the xenotransplanted Os and the host at histological, immunohistochemical, ultrastructural, and molecular level, and to evaluate if this model could be used in testing new anti-angiogenic drugs. Three xenotransplanted human Os were evaluated. Tumor pieces 3-4 mm in size were implanted subcutaneously on the back of athymic Balb-c nude mice (n = 14). The animals were killed at 24, 48, and 72 h and 7, 14, 21, and 28 days after implantation. Tumor samples were either fixed in 10 % formaldehyde and embedded in paraffin for histological analysis, or fixed with glutaraldehyde (2 %) for electron microscopy or retained non-fixed for molecular analysis (ELISA and qRT-PCR). Morphologically, intense neo-vasculogenesis within tumor parenchyma was present between the first and third week after transplantation. Immunohistochemistry demonstrated overexpression of VEGF and their receptors together with PDFGFRA 24-48 h after tumor implantation. Additionally, neoplastic cells co-expressed chemokines (CXCL9, CXCL10, and GRO) and their receptors. Molecular studies showed two expression profiles, distinguishing an early and a late phase in the angiogenic process. In Os, our model showed two stages of induced angiogenesis, with close association between histological and molecular events. This approximation could be of use for testing the effect of different anti-angiogenic agents.

show abstract

Section: Discussionmentioning

confidence: 98%

The early stages of tumor angiogenesis in human osteosarcoma: a nude mice xenotransplant model

et al. 2015

View full text Add to dashboard Cite

show abstract

“…When tumors exceed the size of 1-2 mm, diffusion becomes insufficient to maintain tumor growth, and angiogenesis can occur to help prevent necrosis [83]. Vascular Endothelial Growth Factor (VEGF) is essential in tumor angiogenesis and progression [84].…”

Section: Vascular Endothelial Growth Factor Inhibitorsmentioning

confidence: 99%

Beyond standard therapy: drugs under investigation for the treatment of gastrointestinal stromal tumor

Alturkmani

Pessetto

Godwin

2015

Expert Opinion on Investigational Drugs

View full text Add to dashboard Cite

Introduction Gastrointestinal stromal tumor (GIST) is the most common non-epithelial malignancy of the GI tract. With the discovery of KIT and later PDGFRA gain-of-function mutations as factors in the pathogenesis of the disease, GIST was the quintessential model for targeted therapy. Despite the successful clinical use of imatinib mesylate, a selective receptor tyrosine kinase (RTK) inhibitor that targets KIT, PDGFRA and BCR-ABL, we still do not have treatment for the long-term control of advanced GIST. Areas covered This review summarizes the drugs that are under investigation or have been assessed in trials for GIST treatment. The article focuses on their mechanisms of actions, the preclinical evidence of efficacy, and the clinical trials concerning safety and efficacy in humans. Expert opinion It is known that KIT and PDGFRA mutations in GIST patients influence the response to treatment. This observation should be taken into consideration when investigating new drugs. RECIST was developed to help uniformly report efficacy trials in oncology. Despite the usefulness of this system, many questions are being addressed about its validity in evaluating the true efficacy of drugs knowing that new targeted therapies do not affect the tumor size as much as they halt progression and prolong survival.

show abstract

“…Understanding the various biological sensitivities of the various histological subtypes of undifferentiated pleomorphic sarcoma may lead to the development of individual therapeutic targeted approaches (33).…”

Section: Discussionmentioning

confidence: 99%

Xenograft models for undifferentiated pleomorphic sarcoma not otherwise specified are essential for preclinical testing of therapeutic agents

et al. 2016

View full text Add to dashboard Cite

Abstract. Undifferentiated pleomorphic sarcoma not otherwise specified belongs to the heterogeneous group of soft tissue tumors. It is preferentially located in the upper and lower extremities of the body, and surgical resection remains the only curative treatment. Preclinical animal models are crucial to improve the development of novel chemotherapeutic agents for the treatment of undifferentiated pleomorphic sarcoma. However, this approach has been hampered by the lack of reproducible animal models. The present study established two xenograft animal models generated from stable non-clonal cell cultures, and investigated the difference in chemotherapeutic effects on tumor growth between undifferentiated pleomorphic sarcoma in vivo and in vitro. The cell cultures were generated from freshly isolated tumor tissues of two patients with undifferentiated pleomorphic sarcoma. For the in vivo analysis, these cells were injected subcutaneously into immunodeficient mice. The mice were monitored for tumor appearance and treated with the most common or innovative chemotherapeutic agents available to date. Furthermore, the same drugs were administered to in vitro cell cultures. The most effective tumor growth inhibition in vitro was observed with doxorubicin and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA), also known as vorinostat. In the in vivo xenograft mouse model, the combination of doxorubicin and the tyrosine kinase inhibitor pazopanib induced a significant tumor reduction. By contrast, treatment with vorinostat did not reduce the tumor growth. Taken together, the results obtained from drug testing in vitro differed significantly from the in vivo results. Therefore, the novel and reproducible xenograft animal model established in the present study demonstrated that in vivo models are required to test potential chemotherapeutic agents for the treatment of undifferentiated pleomorphic sarcoma prior to clinical use, since animal models are more similar to humans, compared with in vitro cell cultures.

show abstract

Anti-angiogenic therapy, a new player in the field of sarcoma treatment

Cited by 30 publications

References 117 publications

The early stages of tumor angiogenesis in human osteosarcoma: a nude mice xenotransplant model

The early stages of tumor angiogenesis in human osteosarcoma: a nude mice xenotransplant model

Beyond standard therapy: drugs under investigation for the treatment of gastrointestinal stromal tumor

Xenograft models for undifferentiated pleomorphic sarcoma not otherwise specified are essential for preclinical testing of therapeutic agents

Contact Info

Product

Resources

About