Abstract：
:The therapeutic efficacy of various genetically engineered macromolecules is determined by their delivery and distribution in tumors. We have recently developed mathematical models which describe the interstitial velocity, pressure, and concentration profiles of macromolecules over the length scale of a solid tumor (Baxter and Jain, Microvas. Res. 1989, 1990, 1991). Nonspecific and specific antibodies and antibody fragments were chosen as typical macromolecules. The focus of the present investigation was microscopic transport, i.e., the distribution of pressure and solutes around individual blood vessels. Analytical solutions were obtained for interstitial velocities and pressures, while the concentration profiles were calculated numerically using the finite element method. The microscopic model describes flow patterns around an individual blood vessel in an infinite medium and concentration profiles around a single blood vessel in a network of capillaries. Our analysis is novel in that it incorporates interstitial convection, asymmetric filtration, and transcapillary convection to describe interstitial transport in tumors. The purpose of this model was to determine the effect of extravascular binding and interstitial convection on the distribution of macromolecules on a microscopic scale and to test the continuum hypothesis assumed in our previously published macroscopic models. An approximate one-dimensional model was compared with a more accurate two-dimensional model. The results of our microscopic model confirm that the continuum hypothesis used in our previous macroscopic model is reasonable. On a microscopic length scale diffusion is dominant, and short range distortions in the flow field do not significantly affect the penetration of macromolecules into the tissue. In addition, our model confirms the results of Fujimori et al. (Cancer Res., 1989) concerning a "binding site barrier." The implications of our results for cancer therapy are also discussed.
journal_name
Microvasc Resjournal_title
Microvascular researchauthors
Baxter LT,Jain RKdoi
10.1016/0026-2862(91)90026-8subject
Has Abstractpub_date
1991-03-01 00:00:00pages
252-72issue
2eissn
0026-2862issn
1095-9319journal_volume
41pub_type
杂志文章abstract：:Electrophysiological characteristics of cultured human umbilical vein endothelial cells (HUVEC) were determined using the patch-clamp technique in the whole cell configuration. In isolated cells, membrane potential, capacitance, and input resistance were (Mean +/- SD) - 16.3 +/- 12.7 mV, 53.9 +/- 26 pF, and 2.3 +/- 1....
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1006/mvre.1994.1012
更新日期：1994-03-01 00:00:00
abstract：:We investigated the expression of cell adhesion molecules on the surface of glomerular endothelial cells (GEC), dermal microvascular endothelial cells (MvE), and umbilical vein endothelial cells (HUVEC) that had or had not been stimulated by cytokines. PECAM-1 was constitutively expressed at a high level on HUVEC but ...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1006/mvre.2001.2356
更新日期：2001-11-01 00:00:00
abstract：:Focal adhesion kinase (FAK) is a key component of cell-substratum adhesions, known as focal adhesion complexes. Growing evidence indicates that FAK is important in maintenance of normal cell survival and that disruption of FAK signaling results in loss of substrate adhesion and anoikis (apoptosis) of anchorage-depende...
journal_title：Microvascular research
pub_type： 杂志文章,评审
doi：10.1016/j.mvr.2011.05.003
更新日期：2012-01-01 00:00:00
abstract：:Skeletal muscle arterioles are known to constrict upon elevation of ambient PO2. While several studies have shown that the endothelium plays an important role in this response, it is not clear how this response is mediated. We examined the oxygen-induced constriction of arterioles in the rat spinotrapezius muscle. Ele...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1006/mvre.1995.1025
更新日期：1995-05-01 00:00:00
abstract：:Excessive generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), by activated neutrophils and endothelial cells, has been implicated in the pathophysiology of endothelial barrier dysfunction. Disruption of the integrity of this barrier markedly increases permeability to fluids, solutes and in...
journal_title：Microvascular research
pub_type： 杂志文章,评审
doi：10.1016/j.mvr.2008.10.005
更新日期：2009-01-01 00:00:00
abstract：:Particle adhesion in vivo is highly dependent on the microvascular environment comprising of unique anatomical, geometrical, physiological fluid flow conditions and cell-particle and cell-cell interactions. Hence, proper design of vascular-targeted drug carriers that efficiently deliver therapeutics to the targeted ce...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/j.mvr.2015.02.004
更新日期：2015-05-01 00:00:00
abstract：:Diabetic retinopathy (DR) is a disease that causes blindness due to vascular leakage or abnormal angiogenesis. Hepatocyte growth factor (HGF) is increased in the serum or vitreous fluid in proliferative diabetic retinopathy (PDR) patients, although the effect of HGF on the blood vessels remains unclear. This study foc...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/j.mvr.2020.104103
更新日期：2021-01-01 00:00:00
abstract：:Microvascular dysfunction contributes to the development of cardiovascular and metabolic disease. This study tested the hypothesis that young obese (BMI>30 kg m(-2)), otherwise healthy, adults (N=15) have impaired microvascular function relative to age and sex matched, lean (BMI<25 kg m(-2)) individuals (N=14). Partic...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/j.mvr.2015.11.007
更新日期：2016-03-01 00:00:00
abstract：:We examined the influence of local cooling (-15 degrees C, 60 sec) on blood flow velocity in nailfold capillaries and on laser Doppler flux (LDF) at the fingertip in 12 patients with primary Raynaud's phenomenon (PRP) and 13 patients with secondary Raynaud's (SRP) in comparison with 10 health controls. Skin temperatur...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1006/mvre.1993.1060
更新日期：1993-11-01 00:00:00
abstract：:The purpose of this study was to investigate reactive hyperemia in the capillary network of human skin in terms of the flow per capillary and the density of flow-active capillaries. Seventeen male subjects 20 to 40 years of age were seated with their right foot placed on the stage of a Leitz epi-ilumination microscope...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/0026-2862(85)90040-8
更新日期：1985-07-01 00:00:00
abstract：:The object of the present study was to employ specific pharmacological agents and the chemical sympatholytic drug 6-hydroxydopamine (6-OHDA) to characterize the neural and adrenergic control of vascular smooth muscle tone in arterioles of the hamster cheek pouch. Arteriolar diameters were measured in the superfused ch...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/0026-2862(85)90008-1
更新日期：1985-01-01 00:00:00
abstract：:Cardiovascular diseases, among all diseases, are taking the most victims worldwide. Coronary artery occlusion, takes responsibility of about 30% of the yearly global deaths in the world (Heart Disease and Stroke Statistics 2017 At-a-Glance, 2017), raising the need for viable substitutes for cardiovascular tissues. Dep...
journal_title：Microvascular research
pub_type： 杂志文章,评审
doi：10.1016/j.mvr.2020.104027
更新日期：2020-09-01 00:00:00
abstract：:Reperfusion of the ischemic lung is associated with increased pulmonary vascular resistance and reduced alveolar perfusion in conjunction with an inflammatory response. To determine the contribution of platelet-endothelial interactions, we examined effects of pulmonary ischemia-reperfusion (IR) on platelet adhesion an...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/j.mvr.2003.09.003
更新日期：2004-01-01 00:00:00
abstract：:P120 catenin (p120ctn) belongs to the family of Armadillo repeat-containing proteins, which are believed to have dual functions of cell-cell adhesion and transcriptional regulation. In vascular endothelium, p120ctn is mostly recognized for its cell-cell adhesion function through its ability to regulate VE-cadherin. Th...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/j.mvr.2010.04.001
更新日期：2010-09-01 00:00:00
abstract：:Oxidative stress, which is defined as an imbalance between proxidant and antioxidant systems, is the essential mechanism involving in the ischemic process. During the early stage of brain ischemia, reactive oxygen species (ROS) are increased. Increased ROS are thought of a consequence of brain ischemia and exacerbatin...
journal_title：Microvascular research
pub_type： 杂志文章,评审
doi：10.1016/j.mvr.2018.12.005
更新日期：2019-05-01 00:00:00
abstract：:In this paper we quantitatively investigate the hypothesis proposed by Michel (Exp. Physiol. 82, 1-30, 1997) and Weinbaum (Ann. Biomed. Eng. 26, 1-17, 1998) that the Starling forces are determined by the local difference in the hydrostatic and colloid osmotic pressure across the endothelial surface glycocalyx, which w...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1006/mvre.1999.2177
更新日期：1999-11-01 00:00:00
abstract：:Nitrate supplementation in the form of beetroot juice has been shown to increase nitric oxide (NO) where nitrate can be reduced to nitrite and, subsequently, to NO through both nitric oxide synthase (NOS)-dependent and -independent pathways. We tested the hypothesis that nitrate supplementation would augment the NO co...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/j.mvr.2014.12.002
更新日期：2015-03-01 00:00:00
abstract：:In preeclampsia, invasion of intrauterine decidual blood vessels by placental cytotrophoblasts is significantly reduced. This study examined the secretion of matrix metalloproteinases (MMP) by cultured human decidual endothelial cells from normal (NDEC) and preeclamptic (PEDEC) pregnancies. MMPs secreted into the cult...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1006/mvre.1998.2142
更新日期：1999-05-01 00:00:00
abstract：:Methods currently available for the examination of the retinal vasculature of laboratory animals have significant drawbacks. Fluorescein angiography of rodent eyes is hampered by a poor view of the peripheral retina and difficulty in performing fundus photography. Methods of staining or filling retinal vessels are unr...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1006/mvre.1993.1042
更新日期：1993-09-01 00:00:00
abstract：:Reduced lung capillary expression of angiotensin I-converting enzyme (ACE), a key enzyme in cardiovascular pathophysiology, and of caveolin-1, an important regulator of endothelial cell signalling, has been demonstrated in various models of pulmonary arterial hypertension (PAH). We addressed the relationship between P...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/j.mvr.2010.04.008
更新日期：2010-09-01 00:00:00
abstract：:Red blood cell (RBC)-plasma suspensions with a hematocrit of 10-12% were forced to flow through microchannels (equivalent diameter 6 microns, equivalent length 20 microns, 2600 in parallel) by applying a pressure difference of 20 cm H2O. Transit times for 100 microliters of fresh suspensions from 33 healthy male subje...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1006/mvre.1994.1017
更新日期：1994-03-01 00:00:00
abstract：:The contribution of the pleural mesothelium to pleural liquid and protein transport is still vigorously debated. Recent in vitro studies of stripped pleural membrane and free-standing pericardium have demonstrated active ion solute coupled transport of liquid and transcytosis of protein. However, the relative contribu...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/j.mvr.2005.10.003
更新日期：2005-11-01 00:00:00
abstract：:Recently the zebrafish has emerged as a promising vertebrate model of lymphatic vasculature development. The establishment of numerous transgenic lines that label the lymphatic endothelium in the zebrafish has allowed the fine examination of the developmental timing and the anatomy of their lymphatic vasculature. Alth...
journal_title：Microvascular research
pub_type： 杂志文章,评审
doi：10.1016/j.mvr.2014.06.001
更新日期：2014-11-01 00:00:00
abstract：:An intravital microscopic method for quantitative measurement of interstitial concentrations of fluorescent tracers has been applied to the investigation of microvascular permeability in the hamster cheek pouch. Some nanoliters of FITC-dextran mean mol wt (Mw) 20,000, 3000, or sodium fluorescein (Mw 376) were injected...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/0026-2862(86)90009-9
更新日期：1986-01-01 00:00:00
abstract：:Diabetes mellitus (DM) leads to the development of microvascular diseases and is associated with impaired angiogenesis. The presence of vascular endothelial growth factor (VEGF) can block PDGF-BB dependent regulation of neovascularization and vessel normalization. We tested the hypothesis that the inhibition of VEGF i...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/j.mvr.2016.01.005
更新日期：2016-05-01 00:00:00
abstract：OBJECTIVE:In the present study, we used a two-kidney-two-clip (2k2c) stroke-prone renovascular hypertension rat model (RHRSP) to investigate the protective effects of ligustrazine (TMP) on cerebral arteries and to examine PI3K/Akt pathway behavior under this protection. METHODS:The cerebral artery remodeling was induc...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/j.mvr.2019.103938
更新日期：2020-03-01 00:00:00
abstract：:The aim of this study was to analyze the development of vascular architecture as well as vascular morphometry and morphology of anastomosed microvascular free flaps. Free pectoral skin flaps were raised in 25 rats and anastomosed to the femoral vessels in the groin region. CD31 immunohistology was performed after 3, 7...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/j.mvr.2018.03.006
更新日期：2018-07-01 00:00:00
abstract：PURPOSE:The aim of this study was to investigate whether region-dependent endothelial heterogeneity is present within the porcine vortex vein system. METHODS:The superior temporal vortex vein in young adult pig eyes were dissected out and cannulated. The intact vortex vein system down to the choroidal veins was then p...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/j.mvr.2013.06.004
更新日期：2013-09-01 00:00:00
abstract：:A microfluidic device was developed for quantifying the migratory and deformability capabilities of a single tumor cell using direct imaging. It was fabricated using photolithography and is made of polydimethysiloxane. Chemotaxis approach was used for directing cell movement, using 10 microm microgaps to restrict the ...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/j.mvr.2006.06.003
更新日期：2006-11-01 00:00:00
abstract：:Controversy exists concerning whether activation of N-methyl-D-aspartate (NMDA) receptors exerts direct dilator effects on cerebral arteries. The purpose of this study was to examine the responses of isolated piglet arteries to NMDA to determine whether isolated arteries, apart from surrounding neuronal tissue, are ca...
journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/j.mvr.2005.04.007
更新日期：2005-07-01 00:00:00
