Why are tumour blood vessels abnormal and why is it important to know?

Ja, Nagy; Sh, Chang; Am, Dvorak; Hf, Dvorak

doi:10.1038/sj.bjc.6604929

Cited by 513 publications

(462 citation statements)

References 29 publications

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“…The microenvironmental abundance of VEGF and other proangiogenic factors drives continual angiogenesis and the production of an abnormal blood vessel network (Jain 2005a;Nagy et al 2009). Structurally, vessels are often dilated, weave a tortuous path, and show heterogeneity of distribution such that certain areas within a tumor are hypovascular and others hypervascular (Less et al 1991(Less et al , 1997Yuan et al 1996;Tong et al 2004;Jain 2005b;Baish et al 2011).…”

Section: Vascular Abnormalities In Solid Tumorsmentioning

confidence: 99%

Vascular Normalization as a Therapeutic Strategy for Malignant and Nonmalignant Disease

Goel

Wong

Jain

2011

Cold Spring Harbor Perspectives in Medicine

300

267

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Pathological angiogenesis-driven by an imbalance of pro-and antiangiogenic signaling-is a hallmark of many diseases, both malignant and benign. Unlike in the healthy adult in which angiogenesis is tightly regulated, such diseases are characterized by uncontrolled new vessel formation, resulting in a microvascular network characterized by vessel immaturity, with profound structural and functional abnormalities. The consequence of these abnormalities is further modification of the microenvironment, often serving to fuel disease progression and attenuate response to conventional therapies. In this article, we present the "vascular normalization" hypothesis, which states that antiangiogenic therapy, by restoring the balance between pro-and antiangiogenic signaling, can induce a more structurally and functionally normal vasculature in a variety of diseases. We present the preclinical and clinical evidence supporting this concept and discuss how it has contributed to successful treatment of both solid tumors and several benign conditions.

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Section: Vascular Abnormalities In Solid Tumorsmentioning

confidence: 99%

Vascular Normalization as a Therapeutic Strategy for Malignant and Nonmalignant Disease

Goel

Wong

Jain

2011

Cold Spring Harbor Perspectives in Medicine

300

267

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“…Solid tumors possess unique pathophysiological vasculatures that cannot be found in normal tissues or organs [1], including the hyper vasculatures, the defective vascular architecture, the lack of lymphatic drainage and the extensive production of a number of permeability mediators [2][3][4][5]. These characters are known as the enhanced permeability and retention (EPR) effects that have been widely used to enhance the tumor selectivity of antitumor nanomedicines [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

A highly efficient and tumor vascular-targeting therapeutic technique with size-expansible gadofullerene nanocrystals

Zhen

Shu

et al. 2015

Sci. China Mater.

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It has long been a dream to achieve tumor targeting therapy that can efficiently reduce the toxicity and severe side effects of conventional antitumor chemotherapeutic agents. Taking advantage of the abnormalities of tumor vasculature, we demonstrate here a new powerful tumor vascular-targeting therapeutic technique for solid cancers that applies advanced nanotechnology to cut off the nutrient supply of tumor cells by physically destroying the abnormal tumor blood vessels. Water soluble magnetic Gd@C82 nanocrystals of the chosen sizes are deliberately designed with abilities to penetrate into the leaky tumor blood vessels. By triggering the radiofrequency induced phase transition of gadofullerene nanocrystals while extravasating the tumor blood vessel, the explosive structural change of nanoparticles generates a devastating impact on abnormal tumor blood vessels, resulting in a rapid and extensive ischemia necrosis and shrinkage of the tumors. This unprecedented target-specific physiotherapy is found to work perfectly for advanced and refractory solid tumors.

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“…These include disorganization of the vascular architecture, lack of apparent separation of arterioles from venules, lack of appropriate coverage of perivascular (mural) cells, incomplete basement membrane, and high leakiness (1)(2)(3)(4). These pathological features of the tumor vasculature dictate the abnormal microenvironment within tumor tissues that often produce an imbalanced ratio between angiogenic factors and inhibitors (5).…”

mentioning

confidence: 99%

Vascular endothelial growth factor-dependent spatiotemporal dual roles of placental growth factor in modulation of angiogenesis and tumor growth

Xiao

Zhang

Yang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Placental growth factor (PlGF) remodels tumor vasculatures toward a normalized phenotype, which affects tumor growth, invasion and drug responses. However, the coordinative and spatiotemporal relation between PlGF and VEGF in modulation of tumor angiogenesis and vascular remodeling is less understood. Here we report that PlGF positively and negatively modulate tumor growth, angiogenesis, and vascular remodeling through a VEGF-dependent mechanism. In two independent tumor models, we show that PlGF inhibited tumor growth and angiogenesis and displayed a marked vascular remodeling effect, leading to normalized microvessels with infrequent vascular branches and increased perivascular cell coverage. Surprisingly, elimination of VEGF gene (i.e., VEGF-null) in PlGF-expressing tumors resulted in ( i ) accelerated tumor growth rates and angiogenesis and ( ii ) complete attenuation of PlGF-induced vascular normalization. Thus, PlGF positively and negatively modulates tumor growth, angiogenesis, and vascular remodeling through VEGF-dependent spatiotemporal mechanisms. Our data uncover molecular mechanisms underlying the complex interplay between PlGF and VEGF in modulation of tumor growth and angiogenesis, and have conceptual implication for antiangiogenic cancer therapy.

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Why are tumour blood vessels abnormal and why is it important to know?

Cited by 513 publications

References 29 publications

Vascular Normalization as a Therapeutic Strategy for Malignant and Nonmalignant Disease

Vascular Normalization as a Therapeutic Strategy for Malignant and Nonmalignant Disease

A highly efficient and tumor vascular-targeting therapeutic technique with size-expansible gadofullerene nanocrystals

Vascular endothelial growth factor-dependent spatiotemporal dual roles of placental growth factor in modulation of angiogenesis and tumor growth

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