Medial regression and its functional significance in tumor-supplying host arteries. A morphometric study of hepatic arteries in human livers with hepatocellular carcinoma

Suzuki, Masanori; Takahashi, Tohru; Sato, Toshio

doi:10.1002/1097-0142(19870201)59:3<444::aid-cncr2820590316>3.0.co;2-5

Cited by 43 publications

(11 citation statements)

References 5 publications

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“…Experiments showed that elevating blood pressure by infusing angiotensin increased tumor blood flow by two to six times the normal rate, whereas blood flow in other tissues and organs remained constant, demonstrating that tumors do not posses the homeostatic properties of normal organs (Maeda 2001, Suzuki et al 1987. As reviewed by Maeda (2010), increasing tumor blood flow through dosages of angiotensin resulted in improved macromolecular drug delivery.…”

Section: The Enhanced Permeability and Retention Effectmentioning

confidence: 99%

The Fluid Mechanics of Cancer and Its Therapy

Koumoutsakos

Pivkin

Milde

2013

Annu. Rev. Fluid Mech.

120

108

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Fluid mechanics is involved in the growth, progression, metastasis, and therapy of cancer. Blood vessels transport oxygen and nutrients to cancerous tissues, provide a route for metastasizing cancer cells to distant organs, and deliver drugs to tumors. The irregular and leaky tumor vasculature is responsible for increased interstitial pressure in the tumor microenvironment, whereas multiscale flow-structure interaction processes control tumor growth, metastasis, and nanoparticle-mediated drug delivery. We outline these flow-mediated processes, along with related experimental and computational methods for the diagnosis, predictive modeling, and therapy of cancer. 325

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Section: The Enhanced Permeability and Retention Effectmentioning

confidence: 99%

The Fluid Mechanics of Cancer and Its Therapy

Koumoutsakos

Pivkin

Milde

2013

Annu. Rev. Fluid Mech.

120

108

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“…(11) (iii) defective vascular architecture, such as the lack of a smooth muscle layer and large gaps between vascular endothelial cells; (12,13) and (iv) impaired lymphatic clearance from the tumor interstitial space. (14)(15)(16) The increased vascular permeability and defective vascular structure allow molecules larger than those subject to renal clearance (i.e.…”

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confidence: 99%

Carbon monoxide, generated by heme oxygenase‐1, mediates the enhanced permeability and retention effect in solid tumors

et al. 2012

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The enhanced permeability and retention (EPR) effect is a unique pathophysiological phenomenon of solid tumors that sees biocompatible macromolecules (>40 kDa) accumulate selectively in the tumor. Various factors have been implicated in this effect. Herein, we report that heme oxygenase-1 (HO-1; also known as heat shock protein 32) significantly increases vascular permeability and thus macromolecular drug accumulation in tumors. Intradermal injection of recombinant HO-1 in mice, followed by i.v. administration of a macromolecular Evans blue-albumin complex, resulted in dose-dependent extravasation of Evans blue-albumin at the HO-1 injection site. Almost no extravasation was detected when inactivated HO-1 or a carbon monoxide (CO) scavenger was injected instead. Because HO-1 generates CO, these data imply that CO plays a key role in vascular leakage. This is supported by results obtained after intratumoral administration of a CO-releasing agent (tricarbonyldichlororuthenium(II) dimer) in the same experimental setting, specifically dose-dependent increases in vascular permeability plus augmented tumor blood flow. In addition, induction of HO-1 in tumors by the water-soluble macromolecular HO-1 inducer pegylated hemin significantly increased tumor blood flow and Evans blue-albumin accumulation in tumors. These findings suggest that HO-1 and ⁄ or CO are important mediators of the EPR effect. Thus, anticancer chemotherapy using macromolecular drugs may be improved by combination with an HO-1 inducer, such as pegylated hemin, via an enhanced EPR effect. (Cancer Sci 2012; 103: 535-541) C onventional chemotherapy with small molecule drugs has been used for many types of cancer for decades. However, the therapeutic efficacy remains less than optimal, mostly because of a lack of tumor selectivity, which results in severe adverse side effects and prevents the use of high drug doses.(1)The development of tumor-targeted chemotherapy is critically important for more successful treatment.During investigations of targeting drugs to tumors, Matsumura and Maeda (2) found that macromolecular agents larger than 40 kDa selectively accumulate and remain in tumor tissues for long periods. This unique phenomenon in the blood vasculature of solid tumor tissues is quite different from that in normal tissues and was attributed to the unique anatomic and pathophysiologic characteristics of solid tumors. These features include: (i) extensive angiogenesis and hence high vascular density; (3,4) (ii) extensive extravasation (vascular permeability) induced by various vascular mediators, including bradykinin, (5-7) nitric oxide (NO), (7,8) vascular endothelial growth factor (VEGF), (9,10) prostaglandins produced via cyclo-oxygenases,and matrix metalloproteinases;(11) (iii) defective vascular architecture, such as the lack of a smooth muscle layer and large gaps between vascular endothelial cells; (12,13) and (iv) impaired lymphatic clearance from the tumor interstitial space. (14)(15)(16) The increased vascular permeability and defective vas...

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“…Another factor that can play a role is the opposing forces that govern the high permeability of the tumor vasculature versus the interstitial fluid pressure. Collectively as a result of these vascular flow changes, tumor vessels are often susceptible to blood clot formation [5,57,58]. Finally, rapidly proliferating cancer cells generate a solid stress on tissue, which may contribute to flow effects (Fig.…”

Section: Considerations Of Blood Flowmentioning

confidence: 99%

Vascular targeting of nanoparticles for molecular imaging of diseased endothelium

Atukorale

Covarrubias

Bauer

et al. 2017

Advanced Drug Delivery Reviews

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This review seeks to highlight the enormous potential of targeted nanoparticles for molecular imaging applications. Being the closest point-of-contact, circulating nanoparticles can gain direct access to targetable molecular markers of disease that appear on the endothelium. Further, nanoparticles are ideally suitable to vascular targeting due to geometrically enhanced multivalent attachment on the vascular target. This natural synergy between nanoparticles, vascular targeting and molecular imaging can provide new avenues for diagnosis and prognosis of disease with quantitative precision. In addition to the obvious applications of targeting molecular signatures of vascular diseases (e.g., atherosclerosis), deep-tissue diseases often manifest themselves by continuously altering and remodeling their neighboring blood vessels (e.g., cancer). Thus, the remodeled endothelium provides a wide range of targets for nanoparticles and molecular imaging. To demonstrate the potential of molecular imaging, we present a variety of nanoparticles designed for molecular imaging of cancer or atherosclerosis using different imaging modalities.

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Medial regression and its functional significance in tumor-supplying host arteries. A morphometric study of hepatic arteries in human livers with hepatocellular carcinoma

Cited by 43 publications

References 5 publications

The Fluid Mechanics of Cancer and Its Therapy

The Fluid Mechanics of Cancer and Its Therapy

Carbon monoxide, generated by heme oxygenase‐1, mediates the enhanced permeability and retention effect in solid tumors

Vascular targeting of nanoparticles for molecular imaging of diseased endothelium

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