Cancer and Metastasis Reviews

, Volume 6, Issue 4, pp 559–593 | Cite as

Transport of molecules across tumor vasculature

  • Rakesh K. Jain
Article

Abstract

The vascular-extravascular exchange of fluid and solute molecules in a tissue is determined by three transport parameters (vascular permeability, P, hydraulic conductivity, Lp, and reflection coefficient, σ); the surface area for exchange, A; and the transluminal concentration and pressure gradients. The transport parameters and the exchange area for a given molecule are governed by the structure of the vessel wall. In general, tumor vessels have wide interendothelial junctions; large number of fenestrae and transendothelial channels formed by vesicles; and discontinuous or absent basement membrane. While these factors favor movement of molecules across tumor vessels, high interstitial pressure and low microvascular pressure may retard extravasation of molecules and cells, especially in large tumors. These characteristics of the transvascular transport have significant implications in tumor growth, metastasis, detection and treatment.

Key words

vascular permeability hydraulic conductivity reflection coefficient microvascular pressure interstitial pressure cancer detection and treatment 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Jain RK, Weissbrod J, Wei J: Mass transfer in tumors: Characterization and applications in chemotherapy. Advances in Cancer Research 21: 37–47, 1980Google Scholar
  2. 2.
    Gerlowski LE, Jain RK: Physiologically based pharmacokinetics: Principles and applications. J Pharm Sci, 72 (10): 1103–1127, 1983Google Scholar
  3. 3.
    Jain RK: Mass and heat transfer in tumors. Advances in Transport Process 3: 205–339, 1984Google Scholar
  4. 4.
    Jain RK: Transport of macromolecules in tumor microcirculation. Biotech Prog 1: 81–84, 1985Google Scholar
  5. 5.
    Poste G: Drug targeting in cancer therapy. In: Gregoriadis G, Poste G, Senior J, Trouet A (eds) Receptor-mediated Targeting of Drugs. Plenum Publishing Corporation, New York, 1985, pp 427–474Google Scholar
  6. 6.
    Schlom J: Basic principles and applications of monoclonal antibodies in the management of carcinomas. Cancer Res 46: 3225–3238, 1986Google Scholar
  7. 7.
    Winkler C (editor): Nuclear Medicine in Clinical Oncology. New York: Springer-Verlag, 1986Google Scholar
  8. 8.
    Jain RK: Transport of molecules in the tumor interstitium: A review. Cancer Res, 47: 3038–3050, 1987Google Scholar
  9. 9.
    Jain RK, Ward-Hartley K: Tumor blood flow: Characterization, modifications, and role in hyperthermia. I.E.E.E. Trans Sonics and Ultrasonics, SU-31 (5): 504–526, 1984Google Scholar
  10. 10.
    Poste G, Kirsh R, Bugelski P: Liposomes as a drug delivery system in cancer therapy. In: Sunkara P (ed) Novel Approaches to Cancer Chemotherapy. Academic Press, New York, 1984, pp 165–230Google Scholar
  11. 11.
    Weiss L. Principles of Metastasis, New York, Academic Press, 1985Google Scholar
  12. 12.
    Kawaguchi T, Nakamura K: Analysis of the lodgement and extravasation of tumor cells in experimental models of hematogenous metastasis. Cancer and Metastasis Reviews 5: 77–94, 1986Google Scholar
  13. 13.
    Jain R, Ward-Hartley K: Dynamics of cancer cell interactions with microvasculature and interstitium. Biorheology 24: 117–125, 1987Google Scholar
  14. 14.
    Starling EH: On the absorption of fluids from the connective tissue spaces. J Physiol (London) 19: 312–326, 1896Google Scholar
  15. 15.
    Gullino PM: Extracellular compartments of solid tumors. In: Becker FF (ed) Cancer, Volume 3, Plenum Press, New York, 1975, pp 327–354Google Scholar
  16. 16.
    Wiedeman MP, Tuma RF, Mayrovitz HN: An Introduction to Microcirculation, New York, Academic Press, 1981Google Scholar
  17. 17.
    Wiedeman MP: Architecture. In: Renkin EM, Michel CC (eds) Handbook of Physiology — The Cardiovascular System, Section 2, Volume IV, Microcirculation, Chapter 2. American Physiological Society, Bethesda, MD, 1984, pp 11–40Google Scholar
  18. 18.
    Simionescu M, Simionescu N: Ultrastructure of the microvascular wall: functional correlations. In: Renkin EM, Michel CC (eds) Handbook of Physiology — The Cardiovascular System, Section 2, Volume IV, Microcirculation, Chapter 3. American Physiological Society, Bethesda, MD, 1984, pp 41–101Google Scholar
  19. 19.
    Persson CGA, Svensjö E: Vascular responses and their suppression: drugs interfering with venular permeability. Handbook of Inflammation, 5: 61–82, 1985Google Scholar
  20. 20.
    Folkman J: Tumor angiogenesis. Adv Cancer Res 43: 175–203, 1985Google Scholar
  21. 21.
    Warren BA: The vascular morphology of tumors. In: Peterson HI (ed) Tumor Blood Circulation, Chapter 1. CRC Press Inc., Boca Raton FL, 1979, pp 1–47Google Scholar
  22. 22.
    Warren BA:In vivo and electron microscopic study of vessels in a hemangiopericytoma of the hamster. Angiologica, 5: 230, 1968Google Scholar
  23. 23.
    Warren BA: The ultrastructure of the microcirculation of the advancing edge of Walker 256 carcinoma. Microvasc Res 2: 443–453, 1970Google Scholar
  24. 24.
    Groscurth P, Kistler G: Human renal cell carcinoma in the nude mouse: long term observations. Beitr Pathol 160: 337, 1977Google Scholar
  25. 25.
    Hirano A, Matsui T: Vascular structures in brain tumors. Human Pathol 6: 611–621, 1975Google Scholar
  26. 26.
    Vogel AW: Intratumoral vascular changes with increased size of a mammary adenocarcinoma: New methods and results. J Natl Cancer Inst 34: 571–578, 1965Google Scholar
  27. 27.
    Warren BA, Chauvin WJ: Transmission and scanning electron microscopy of renal adenocarcinoma. Ann Royal Con Phys Surg Can 10: 74, 1977Google Scholar
  28. 28.
    Dvorak HF, Singer DR, Dvorak AM, Harvery VS, McDonagh J: Regulation of extravascular coagulation by microvascular permeability. Science 227: 1059–1061, 1985Google Scholar
  29. 29.
    Warren BA, Shubik P: The growth of the blood supply to melanoma transplants in the hamster cheek pouch chamber. Lab Invest 15: 464, 1966Google Scholar
  30. 30.
    Cliff WJ: Observations on healing tissue: a combined light and electron microscopic investigation. Philos Trans Roy Soc, London, Series B, 246: 305–325, 1963Google Scholar
  31. 31.
    Warren BA, Shubik P, Feldman R: Metastasis via the blood stream: the method of intravasation of tumor cells in a transplantable melanoma of the hamster. Cancer Lett 4: 245–251, 1978Google Scholar
  32. 32.
    Krogh A: The Anatomy and Physiology of Capillaries. New Haven, CT: Yale Univ Press, 1929, p 326Google Scholar
  33. 33.
    Landis EM: Micro-injection studies of capillary permeability. II. The relation between capillary pressure and the rate at which fluid passes through the walls of single capillaries. Am J Physiol 82: 217–238, 1927Google Scholar
  34. 34.
    Pappenheimer JR, Renkin EM, Borrero LM: Filtration, diffusion and molecular sieving through peripheral capillary membranes: A contribution to the pore theory of capillary permeability. Am J Physiol 167: 13–46, 1951Google Scholar
  35. 35.
    Palade GE: Fine structure of blood capillaries. [Abstract], J Appl Physiol 24: 1424, 1953Google Scholar
  36. 36.
    Karnovsky MJ: The ultrastructural basis of capillary permeability studies with peroxidase as a tracer. J Cell Biol 35: 213–236, 1967Google Scholar
  37. 37.
    Simionescu N, Simionescu M, Palade GE: Permeability of muscle capillaries to small heme-peptides: Evidence for the existence of patent transendothelial channels. J Cell Biol 64: 586–607, 1975Google Scholar
  38. 38.
    Bruns RR, Palade GE: Studies on blood capillaries. I. General organization of blood capillaries in muscle. J Cell Biol 37: 244–276, 1968Google Scholar
  39. 39.
    Bruns RR, Palade GE: Studies on blood capillaries. II. Transport of ferritin molecules across the wall of muscle capillaries. J Cell Biol 37: 277–299, 1968Google Scholar
  40. 40.
    Bundgaard M, Frokjaer-Jensen J, Crone C: Endothelial plasmalemmal vesicles as elements in a system of branching invaginations from the cell surface. Proc Natl Acad Sci USA 76: 6439–6442, 1979Google Scholar
  41. 41.
    Crone C: The function of capillaries. Recent Adv in Physiology 10: 125–162, 1984Google Scholar
  42. 42.
    Renkin EM, Michel CC (eds): Handbook of Physiology, Section 2 — The Cardiovascular System, Volume IV — Microcirculation. Am Physiological Soc, Bethesda, MD, 1984Google Scholar
  43. 43.
    Renkin EM: Multiple pathways of capillary permeability. Circ Res 41: 735–743, 1977Google Scholar
  44. 44.
    Duling BR, Berne RM: Longitudinal gradients in periarteriolar oxygen tension. Circ Res 27: 669–678, 1970Google Scholar
  45. 45.
    Scow RO, Blanchette-Mackie EJ, Smith LC: Role of capillary endothelium in the clearance of chylomicrons. Circ Res 39: 149–162, 1978Google Scholar
  46. 46.
    Taylor AE, Granger DN: Exchange of macromolecules across the microcirculation. In: Renkin EM, Michel CC (eds) Handbook of Physiology — The Cardiovascular System, Section 2, Volume IV, MIcrocirculation, Chapter 11. American Physiology Society, Bethesda, MD, 1984, pp 467–520Google Scholar
  47. 47.
    Curry FE: Mechanics and thermodynamics of transcapillary exchange. In: Renkin EM, Michel CC (eds) Handbook of Physiology-The Cardiovascular System, Volume IV, Microcirculation, Chapter 8. American Physiological Soc, Bethesda, MD, 1984, pp 309–374Google Scholar
  48. 48.
    Underwood JCE, Carr I: The ultrastructure and permeability characteristics of the blood vessels of a transplantable rat sarcoma. J Pathol 107: 157–166, 1972Google Scholar
  49. 49.
    Papadimitriou JM, Woods AE: Structural and functional characteristics of the microcirculation in neoplasms. J Pathol 116: 65, 1975Google Scholar
  50. 50.
    Ward JD, Hadfield MG, Becker DP, Lovings ET: Endothelial fenestrations and other vascular alterations in primary melanoma of the central nervous system. Cancer 34: 1982–1991, 1976Google Scholar
  51. 51.
    Waggener JD, Beggs JL: Vasculature of neural neoplasma. Adv Neurol 15: 27, 1976Google Scholar
  52. 52.
    Kedem O, Katchalsky A: Thermodynamic analysis of the permeability of biological membranes to non-electrolytes. Biochim Biophys Acta 27: 229–245, 1958Google Scholar
  53. 53.
    Staverman AJ: The theory of measurement of osmotic pressure. Rec Trav Chim Pays-Bas, 70: 344–352, 1951Google Scholar
  54. 54.
    Kedem O, Katchalsky A: A physical interpretation of the phenomenological coefficients of membrane permeability. J Gen Physiol 45: 143–179, 1961Google Scholar
  55. 55.
    Patlak CS, Goldstein DA, Hoffman JF: The flow of solute and solvent across a two-membrane system. J Theor Biol 5: 426–442, 1963Google Scholar
  56. 56.
    Crone C, Levitt DG: Capillary permeability to small solutes. In: Renkin EM, Michel CC (eds) Handbook of Physiology — The Cardiovascular System, Section 2, Volume IV, Microcirculation, Chapter 10. American Physiological Society, Bethesda, MD, 1984, pp 411–466Google Scholar
  57. 57.
    Michel CC: Fluid movements through capillary wall. In: Renkin EM, Michel CC (eds) Handbook of Physiology — The Cardiovascular System, Section 2, Volume IV, Microcirculation, Chapter 9. American Physiological Society, Bethesda, MD, 1984, pp 375–409Google Scholar
  58. 58.
    Landis EM, Gibbon Jr JH: The effects of temperature and of tissue pressure on the movement of fluid through the human capillary wall. J Clin Invests 12: 105–138, 1933Google Scholar
  59. 59.
    Gore RW, McDonagh PF: Fluid exchange across single capillaries. Annual Rev Physiol 42: 337–357, 1980Google Scholar
  60. 60.
    Curry FE, Huxley VH, Sarelius IH: Techniques in the microcirculation: Measurements of permeability, pressure and flow. In: Linden RJ (ed) Techniques in the Life Sciences-Cardiovascular Physiology, Vol. P3/1. Elsevier, New York, 1983, pp 1–34Google Scholar
  61. 61.
    Zweifach BW, Intaglietta M: Mechanics of fluid movement across single capillaries in the rabbit. Microvasc Res 1: 83–101, 1968Google Scholar
  62. 62.
    Smaje LH, Zweifach BW, Intaglietta M: Micropressures and capillary filtration coefficients in single vessels of the cremaster muscle of the rat. Microvasc Res 2: 96–110, 1970Google Scholar
  63. 63.
    Lee JS, Smaje LH, Zweifach BW: Fluid movement in occluded single capillaries of rabbit omentum. Circ Res 28: 358–370, 1971Google Scholar
  64. 64.
    Gore RW: Fluid exchange across single capillaries in rat intestinal muscle. Am J Physiol 242 (Heart Circ Physiol) 11: H268-H287, 1982Google Scholar
  65. 65.
    Clough G, Smaje LH: Changes in capillary permeability in scurvy. Biorheology 14: 203, 1977 [Abstract]Google Scholar
  66. 66.
    McDonagh PF, Gore RW: Comparison of hydraulic conductivities in single capillaries of red versus white skeletal muscle. [Abstract]. Microvasc Res 15: 269, 1978Google Scholar
  67. 67.
    Frazer PA, Smaje LH, Verrinder A: Microvascular pressure and filtration coefficients in the cat mesentery. J Physiol, London, 283: 439–456, 1978Google Scholar
  68. 68.
    Smaje LH, Frazer PA, Clough G: The distensibility of single capillaries and venules in the cat mesentery. Microvasc Res 20: 358–376, 1980Google Scholar
  69. 69.
    Michel CC, Mason JC, Curry FE, Tooke JE, Hunter PA: A development of the Landis technique for measuring the filtration coefficient of individual capillaries in the frog mesentery. Q.J. Exp Physiol 59: 283–309, 1974Google Scholar
  70. 70.
    Curry FE, Mason JC, Michel CC: Osmotic reflection coefficients of capillary walls to low molecular weight hydrophilic solutes measured in single perfused capillaries of the frog mesentery. J Physiol 261: 319–336, 1976Google Scholar
  71. 71.
    Levick JR, Michel CC: A densitometric method for determining the filtration coefficients of single capillaries in the frog mesentery. Microvasc Res 13: 141–151, 1977Google Scholar
  72. 72.
    Mason JC, Curry FE, Michel CC: The effects of protein upon the filtration coefficient of individually perfused frog mesenteric capillaries. Microvasc Res 13: 185–202, 1977Google Scholar
  73. 73.
    Michel CC: Filtration coefficients and osmotic reflection coefficients of the walls of single frog mesenteric capillaries. J Physiol, London, 309: 355, 1980Google Scholar
  74. 74.
    Curry FE: Permeability coefficients of the capillary wall to low molecular weight hydrophilic solutes measured in single perfused capillaries of frog mesentery. Microvasc Res 17: 290–308, 1979Google Scholar
  75. 75.
    Curry FE, Frokjaer-Jensen J: Water flow across the walls of single muscle capillaries in the frog, Rana Pipiens. J Physiol 350: 293–307, 1984Google Scholar
  76. 76.
    Mellander S, Oberg B, Odelram H: Vascular adjustments to increased transmural pressure in cat and man with special reference to shifts in capillary fluid transfer. Acta Physiol Scand 61: 34–48, 1964Google Scholar
  77. 77.
    Sejrsen P, Henriksen O, Paaske WP: Effect of orthostatic blood pressure changes upon capillary filtration-absorption rate in the human calf. Acta Physiol Scand 111: 287–291, 1981Google Scholar
  78. 78.
    Folkow B, Mellander S: Measurements of capillary filtration coefficient and its use in studies of the control of capillary exchange. In: Crone C, Lassen NA (eds) Capillary Permeability, Copenhagen: Munksgaard, 1970, p 614–623 (Alfred Benzon Symp. 2)Google Scholar
  79. 79.
    Richardson PDI, Granger DN, Taylor AE: Capillary filtration coefficient: the technique and its application to the small intestine. Cardiovasc Res 13: 547–561, 1979Google Scholar
  80. 80.
    Mortillaro NA, Taylor AE: Interaction of capillary and tissue forces in the cat small intestine. Circ Res 39: 349–358, 1976Google Scholar
  81. 81.
    Diana JN, Long SC, Yao H: Effect of histamine on equivalent pore radius in capillaries of isolated dog hind-limb. Microvasc Res 4: 413–437, 1972Google Scholar
  82. 82.
    Chen HI, Granger HJ, Taylor AE: Interaction of capillary, interstitial and lymphatic forces in the canine hind paw. Circ Res 39: 245–254, 1976Google Scholar
  83. 83.
    Johnson P, Hanson KM: Capillary filtration in the small intestine of the dog. Circ Res 19: 766–773, 1966Google Scholar
  84. 84.
    Guyton AC, Lindsey AW: Effects of elevated left atrial pressure and decreased plasma protein concentration on the development of pulmonary edema. Circ Res 7: 649–657, 1959Google Scholar
  85. 85.
    Gaar Jr KA, Taylor AE, Owens LJ, Guyton AC: Pulmonary capillary pressure and filtration coefficient in the isolated perfused lung. Am J Physiol 213: 910–914, 1967Google Scholar
  86. 86.
    Perl W, Chowdhury P, Chinard FP: Reflection coefficients of dog lung endothelium to small hydrophilic solutes. Am J Physiol 228: 797–809, 1975Google Scholar
  87. 87.
    Drake RE, Smith JH, Gabel JC: Estimation of the filtration coefficient in intact dog lungs. Am J Physiol 238: H430-H438, 1980Google Scholar
  88. 88.
    Renkin EM, Zaun BD: Effects of adrenal hormones on capillary permeability in perfused rat tissues. Am J Physiol 180: 498–502, 1955Google Scholar
  89. 89.
    Rippe B, Kamiya A, Folkow B: Simultaneous measurements of capillary diffusion and filtration exchange during shifts in filtration-absorption and at graded alterations in the capillary permeability surface area product (PS). Acta Physiol Scand 104: 318–336, 1978Google Scholar
  90. 90.
    Vargas F, Johnson JA: Permeability of rabbit heart capillaries to nonelectrolytes. Am J Physiol 213: 87–93, 1967Google Scholar
  91. 91.
    Nicolaysen G: Increase in capillary filtration rate resulting from reduction in the intravascular calcium ion concentration. Acta Physiol Scand 81: 517–527, 1971Google Scholar
  92. 92.
    Wangensteen OD, Lysaker E, Savaryn P: Pulmonary capillary filtration and reflection coefficients in the adult rabbit. Microvasc Res 19: 239–241, 1977Google Scholar
  93. 93.
    Fenstermacher JD, Johnson JA: Filtration and reflection coefficients of the rabbit blood-brain barrier. Am J Physiol 211: 341–346, 1966Google Scholar
  94. 94.
    Erdmann AJ III, Vaughan Jr TR, Brigham KL, Woolverton WC, Staub NC: Effect of increased vascular pressure on lung fluid balance in unanesthetized sheep. Circ Res 37: 271–284, 1975Google Scholar
  95. 95.
    Parker JC, Parker RE, Granger DN, Taylor AE: Vascular permeability and transvascular fluid and protein transport in the dog lung. Circ Res 48: 549–560, 1981Google Scholar
  96. 96.
    Vargas F, Johnson JA: An estimate of reflection coefficients for rabbit heart capillaries. J Gen Physiol 47: 667–677, 1964Google Scholar
  97. 97.
    Curry FE, Huxley VH, Adamson RH: Permeability of single capillaries to intermediate-sized colored solutes. Am J Physiol 245: H495-H505, 1983Google Scholar
  98. 98.
    Vargas FF, Blackshear GL: Transcapillary osmotic flows in thein vitro perfused heart. Am J Physiol, 240 (Heart Circ Physiol, 9): H448-H456, 1981Google Scholar
  99. 99.
    Renkin EM, Curry FE: Transport of water and solutes across capillary endothelium. In: Giebisch G, Tosteson DC (eds) Transport Across Biological Membranes: Transport Organs, Berlin: Springer-Verlag, Vol. 4, p 1–45, 1978Google Scholar
  100. 100.
    Ballard K, Perl W: Osmotic reflection coefficients of canine subcutaneous adipose tissue endothelium. Microvasc Res 16: 224–236, 1978Google Scholar
  101. 101.
    Granger DN, Granger JP, Brace RA, Parker RE, Taylor AE: Analysis of the permeability characteristics of cat intestinal capillaries. Circ Res 44: 335–344, 1979Google Scholar
  102. 102.
    Bassingthwaighte JB, Goresky CG: Modeling in the analysis of solute and water exchange in the microvasculature. In: Renkin EM, Michel CG (eds) Handbook of Physiology — The Cardiovascular System, Section 2, Volume IV, Microcirculation, Chapter 13. American Physiological Society, Bethesda, MD, 1984, pp 549–626Google Scholar
  103. 103.
    Miles AA, Miles EM: Vascular reactions to histamine, histamine-liberator, and leukotaxine in the skin of guinea pigs. J Physiol 118: 228–257, 1952Google Scholar
  104. 104.
    Song CW, Levitt SH: Quantitative study of vascularity in Walker carcinoma 256, Cancer Res 31: 587–589, 1971Google Scholar
  105. 105.
    Clement JJ, Song CW, Levitt SH: Changes in functional vascularity and cell number following X-irradiation of a murine carcinoma. Int J Radiation Oncology, Biol Phys 1: 671–678, 1976Google Scholar
  106. 106.
    Song CW, Kang MS, Rhee JG, Levitt SH: Effect of hyperthermia on vascular function in normal and neoplastic tissues. Ann NY Acad Sci 335: 35–43, 1980Google Scholar
  107. 107.
    Sands H, Shah SA, Gallagher BM: Vascular volume and permeability of human and murine tumors grown in athymic mice. Cancer Lett 27: 15–21, 1985Google Scholar
  108. 108.
    Zweifach BW, Lipowsky HH: Pressure-flow relations in blood and lymph microcirculation. In: Renkin EM, Michel CC (eds) Handbook of Physiology-The Cardiovascular System, Volume IV, Microcirculation, Chapter 7. American Physiological Soc, Bethesda, MD, 1984, pp 251–307Google Scholar
  109. 109.
    O'Connor SW, Bale WF: Accessibility of circulating immunoglobulin G to the extravascular compartment of solid rat tumors. Cancer Res 44: 3719–3723, 1984Google Scholar
  110. 110.
    Fenstermacher JD, Blasberg RG, Patlak CS: Methods for quantifying the transport of drugs across brain barrier systems. Pharmacol Ther 14: 217–248, 1981Google Scholar
  111. 111.
    Gullino PM, Grantham FH: Studies on the exchange of fluids between host and tumor. I. A method for growing ‘tissue-isolated’ tumors in laboratory animals. J Natl Cancer Inst 27: 679–693, 1961Google Scholar
  112. 112.
    Gullino PM: Techniques for the study of tumor physiopathology. Methods in Cancer Research 5: 45–91, 1970Google Scholar
  113. 113.
    Jain RK, Wei J, Gullino PM: Pharmacokinetics of methotrexate in solid tumors. J Pharmacokin Biopharma 7: 181–194, 1979Google Scholar
  114. 114.
    Bjork J, Smedegard G, Svensjo E, Arfors KE: The use of the hamster cheek pouch for intravital microscopy studies of microvascular events. Prog Appl Microcirc 6: 41–53, 1984Google Scholar
  115. 115.
    Baxter LT, Jain RK, Svensjo E: Vascular permeability and interstitial diffusion of macromolecules in the hamster cheek pouch: Effects of vasoactive drugs. Microvasc Res. (in press), 1987Google Scholar
  116. 116.
    Nugent LJ, Jain RK: Monitoring transport in the rabbit ear chamber. Microvasc Res 24: 204–209, 1982Google Scholar
  117. 117a.
    Nugent LJ, Jain RK: Plasma pharmacokinetics and interstitial diffusion of macromolecules in a capillary bed. Am J Physiol 246: H129-H137, 1984Google Scholar
  118. 117b.
    Nugent LJ, Jain RK: Extravascular diffusion in normal and neoplastic tissues. Cancer Res 44: 238–244, 1984Google Scholar
  119. 118.
    Gerlowski LE, Jain RK: Microvascular permeability of normal and neoplastic tissues. Microvasc Res 31: 288–305, 1986Google Scholar
  120. 119.
    Crone C, Frokjer-Jensen J, Friedman JJ, Christensen O: The permeability of single capillaries to potassium ions. J Gen Physiol 71: 195–220, 1978Google Scholar
  121. 120.
    Curry FE, Joyner WL: The effect of histamine, 40/80 and A23187 on albumin permeability in frog venular capillaries. [Abstract]. Fed Proc 45: 1159, 1986Google Scholar
  122. 121.
    Hansen AJ, Lund-Andersen H, Crone C: K+-permeability of the blood-brain barrier, investigated by aid of a K+-sensitive microelectrode. Acta Physiol Scand 101: 438–445, 1977Google Scholar
  123. 122.
    Olesen SP, Crone C: Electrical resistance of muscle capillary endothelium. Biophys J 42: 31–41, 1983Google Scholar
  124. 123.
    Frokjaer-Jensen J: Permeability of single muscle capillaries to potassium ions. Microvasc Res 24: 168–183, 1982Google Scholar
  125. 124.
    Joyner WL, Curry FE: Measurement of albumin permeability coefficients in single capillaries of hamster mesentery. [Abstract]. Fed Proc 45: 583, 1986Google Scholar
  126. 125.
    Jain RK, Gerlowski LE: Extravascular transport in normal and tumor tissues. CRC Crit Rev Oncology/Hematology 5: 115–170, 1986Google Scholar
  127. 126.
    Bassingthwaighte JB, Yipintsoi T, Harvey RB: Microvasculature of the dog left ventricular myocardium. Microvasc Res 7: 229–249, 1974Google Scholar
  128. 127.
    Turek Z: Grandtner M, Kreuzer F: Cardiac hypertrophy, capillary and muscle fiber density, muscle fiber diameter, capillary radius and diffusion distance in the myocardium of growing rats, adapted to a simulated altitude of 3500 m. Pfluegers Arch 335: 19–28, 1972Google Scholar
  129. 128.
    Metzger H, Heuber-Metzger S, Steinacker A, Struber J: Staining PO2 measurement sites in the rat brain cortex and quantitative morphometry of the surrounding capillaries. Pfluegers Arch 338: 21–27, 1980Google Scholar
  130. 129.
    Bar T: The vascular system of the cerebral cortex. In: Brodal A, Hild W, van Limborgh J, Ortmann R, Schiebler TH, Tondury G, Wolff E (eds) Advances in Anatomy, Embryology and Cell Biology, Vol 59, Springer-Verlag, Berlin, 1980Google Scholar
  131. 130.
    Pawlik G, Rackl A, Bing RJ: Quantitative capillary topography and blood flow in the cerebral cortex of cats: anin vivo microscopic study. Brain Res 208: 35–58, 1981Google Scholar
  132. 131.
    Vimtrup B: On the number, shape, structure and surface area of the glomeruli in the kidneys of man and mammals. Am J Anat 41: 123–151, 1928Google Scholar
  133. 132.
    Putter A: Aktive Oberflache und Organfunktion. Z Allg Physiol 12: 125–214, 1911Google Scholar
  134. 133.
    Crone C: Does ‘restricted diffusion’ occur in muscle capillaries? Proc Soc Exp Biol Med 112: 453–455, 1963Google Scholar
  135. 134.
    Renkin EM, Gilmore JP: Glomerular filtration. In: Hamilton WF, Dow P (eds) Handbook of Physiology: Circulation, American Physiological Soc, Washington D.C., 1973Google Scholar
  136. 135.
    Perry MA: Capillary filtration and permeability coefficients calculated from measurements of interendothelial cell junctions in rabbit lung and skeletal muscle. Microvasc Res 19: 142–157, 1980Google Scholar
  137. 136.
    Weibel ER: Morphological basis of alveolar-capillary gas exchange. Physiol Rev 53: 419–495, 1973Google Scholar
  138. 137.
    Eriksson E, Myrhage R: Microvascular dimensions and blood flow in skeletal muscle. Acta Physiol Scand 86: 211–222, 1972Google Scholar
  139. 138.
    Schmid-Schönbein G, Zweifach B, Kovalcheck S: The application of stereological principles to morphometry of the microcirculation in different tissues. Microvasc Res 12: 303–317, 1977Google Scholar
  140. 139.
    Casley-Smith JR, Green HS, Harris JL, Wadey PJ: The quantitative morphology of skeletal muscle capillaries in relation to permeability. Microvasc Res 10: 43–64, 1975Google Scholar
  141. 140.
    Myrhage R, Hudlicka O: The microvascular bed and capillary surface area in the rat extensor halucis propius muscle (EHP). Microvasc Res 11: 315–323, 1976Google Scholar
  142. 141.
    Hilmas D, Gilette EL: Morphometric analyses of the microvasculature of tumors during growth and after X-irradiation. Cancer 33: 103–110, 1974Google Scholar
  143. 142.
    Yamaura H, Sato H: Quantitative studies on the developing vascular system of rat hepatoma. J Natl Cancer Inst 53: 1229–1240, 1974Google Scholar
  144. 143.
    Rous R, Gilding HP, Smith F: A gradient of vascular permeability. J Exp Med 51: 807–830, 1930Google Scholar
  145. 144.
    Ley K, Arfors KE: Segmental differences of microvascular permeability for FITC-dextrans measured in the hamster cheek pouch. Microvasc Res 31: 84–99, 1986Google Scholar
  146. 145.
    Dewey WC: Vascular-extravascular exchange of131l plasma proteins in the rat. Am J Physiol 197: 423–431, 1959Google Scholar
  147. 146.
    Song CW, Levitt SH: Effect of X-irradiation on vascularity of normal tissues and experimental tumor. Radiology 94: 445–447, 1970Google Scholar
  148. 147.
    Peterson HI, Appelgren L, Lundborg G, Rosengren B: Capillary permeability of two transplantable rat tumors as compared with various normal organs of the rat. Bibl Anat 12: 511–518, 1973Google Scholar
  149. 148.
    Peterson HI: Vascular and extravascular spaces in tumors: tumor vascular permeability. In: Peterson HI (ed) Tumor Blood Circulation, pp 77–85. Boca Raton, FL: CRC Press, 1979Google Scholar
  150. 149.
    Groothuis DR, Fischer JM, Pasternak JF, Blasberg RG, Vick NA, Bigner DD: Regional measurements of blood-to-tissue transport in experimental RG-2 rat gliomas. Cancer Res 43: 3368–3373, 1983Google Scholar
  151. 150.
    Blasberg RG, Kobayashi T, Horowitz M, Rice JM, Groothuis D, Molnar P, Fenstermacher JD: Regional blood-to-tissue transport in ethylnitrosourea-induced brain tumors. Ann Neurology 14: 202–215, 1983Google Scholar
  152. 151.
    Molnar P, Blasberg RG, Groothuis DG, Bigner D, Fenstermacher JF: Regional blood-to-tissue transport in avian sarcoma virus (AVS)-induced brain tumors. Neurology 33: 702–711, 1983Google Scholar
  153. 152.
    Blasberg R, Molnar P, Groothuis D, Patlak CS, Owens E, Fenstermacher J: Concurrent measurements of blood flow and transcapillary transport in avian sarcoma virus-induced experimental brain tumors: Implications for chemotherapy. J Pharmacol Expt Therap 231: 724–735, 1984Google Scholar
  154. 153.
    Molnar P, Blasberg RG, Horowitz M, Smith B, Fenstermacher JD: Regional blood-to-tissue transport in RT-g brain tumors. J Neurosurg 58: 874–884, 1983Google Scholar
  155. 154.
    Blasberg RG, Shapiro WR, Molnar P, Patlak CS, Fenstermacher JD: Local blood-to-tissue transport in Walker 256 metastatic brain tumors. J Neuro-Oncology 2: 205–218, 1984Google Scholar
  156. 155.
    Song CW, Sung JH, Clement JJ, Levitt SH: Vascular changes in neuroblastoma of mice following X-irradiation. Cancer Res 34: 2344–2350, 1974Google Scholar
  157. 156.
    Groothuis DR, Fischer JM, Lapin G, Bigner DD, Vick NA: Permeability of different experimental brain tumor models to horseradish peroxidase. J Neuropath Exptl Neurology 41: 164–185, 1982Google Scholar
  158. 157.
    Ackerman NB, Hechmer PA: Studies on the capillary permeability of experimental liver metastases. Surg Gynec Obstet 146: 884–888, 1978Google Scholar
  159. 158.
    Rutili G: Transport of macromolecules in subcutaneous tissue by FITC-dextrans. Dissertation, Univ. Upsaliensis, Uppsala, Sweden, 1978Google Scholar
  160. 159.
    Garlick DG, Renkin EM: Transport of large molecules from plasma to interstitial fluid and lymph in dogs. Amer J Physiol 219: 1595–1605, 1970Google Scholar
  161. 160.
    Butler TP, Grantham FH, Gullino PM: Bulk transfer of fluid in the interstitial compartment of mammary tumors. Cancer Res 35: 512–516, 1975Google Scholar
  162. 161.
    Gullino PM: The internal milieu of tumors. Progr Exp Tumor Res 8: 1–25, 1966Google Scholar
  163. 162.
    Misiewicz M: Microvascular and interstitial pressures in normal and neoplastic tissues. M.S. Thesis, Carnegie Mellon University, 1986Google Scholar
  164. 163.
    Algire GH, Legallais FY: Vascular reactions of normal and malignant tissuesin vivo. IV. The effect of peripheral hypotension on transplanted tumors. J Natl Cancer Inst 12: 399–421, 1951Google Scholar
  165. 164.
    Algire GH: Blood pressure measurements and changes in peripheral vascular bed in unanesthetized mice [Abstract]. Federation Proc 8: 349, 1949Google Scholar
  166. 165.
    Algire GH: Determination of peripheral blood pressure in unanesthetized mice during microscopic observation of blood vessels. J Natl Cancer Inst 14: 865–873, 1954Google Scholar
  167. 166.
    Ide AD, Baker NH, Warren SH: Vascularization of the Brown-Pearce rabbit epithelioma transplant as seen in the transparent ear chamber. Am J Roentgenol 42: 891–899, 1939Google Scholar
  168. 167.
    Eddy HA, Casarett GW: Development of the vascular system in the hamster malignant neurilemmoma. Microvasc Res 6: 63–82, 1973Google Scholar
  169. 168.
    Peters W, Teixeira M, Intaglietta M, Gross JF: Microcirculatory studies in rat mammary carcinoma. I. Transparent chamber method, development of microvasculaturem and pressures in tumor vessels. J Natl Cancer Inst 65: 631–642, 1980Google Scholar
  170. 169.
    Young JS, Griffith HD: The dynamics of parenchymatous embolism in relation to the dissemination of malignant tumors. J Pathol Bacteriol 62: 293–311, 1950Google Scholar
  171. 170.
    Wiig H: Microvascular pressures in DMBA-induced rat mammary tumors. Scand J Clin Lab Invest 42: 165–171, 1982Google Scholar
  172. 171.
    Hori K, Suzuki M, Abe S, Saito S, Sato H: A microocclusion technique for measurement of the microvascular pressure in tumor and subcutis. Japn J Cancer Res (Gann) 74: 122–127, 1983Google Scholar
  173. 172.
    Endrich B, Hammersen F: Morphologic and hemodynamic alterations in capillaries during hyperthermia. In: Anghileri CLJ, Robert J (eds) Hyperthermia in Cancer Treatment, Chapter 2. CRC Press, Boca Raton, FL, 1986Google Scholar
  174. 173.
    Young JS, Lumsden CE, Stalker AL: The significance of the ‘tissue pressure’ of normal testicular and of neoplastic (Brown-Pearce carcinoma) tissue in the rabbit. J Path Bact 62: 313–333, 1950Google Scholar
  175. 174.
    Wiig H, Tveit E, Hultborn R, Reed RK, Weiss L: Interstitial fluid pressure in DMBA-induced rat mammary tumors. Scand J Clin Lab Invest 42: 159–164, 1982Google Scholar
  176. 175.
    Paskins-Hurlburt AJ, Hollenberg NK, Abrams HL: Tumor perfusion in relation to the rapid growth phase and necrosis: Studies on the Walker carcinoma in the rat testicle. Microvasc Res 24: 15–24, 1982Google Scholar
  177. 176.
    Hori K, Suzuki M, Abe I, Saito S: Increased tumor pressure in association with the growth of rat tumors. Japan J Cancer Res (Gann) 77: 65–73, 1986Google Scholar
  178. 177.
    Misiewicz M, Jain RK: Interstitial pressure gradients in VX2 carcinoma. In preparation, 1987Google Scholar
  179. 178.
    Chary SR, Jain RK: Analysis of diffusive and convective recovery of fluorescence after photobleaching — Effect of uniform flow field. Chemical Engineering Communications (in press), 1987Google Scholar
  180. 179.
    Potchen EJ, Kinzie J, Curtis C, Siegel BA, Studer RK: Effect of irradiation on tumor microvascular permeability to macromolecules. Cancer 30: 639–642, 1972Google Scholar
  181. 180.
    Song CW, Levitt SH: Vascular changes in Walker 256 carcinoma of rats following irradiation. Radiology 100: 397–407, 1971Google Scholar
  182. 181.
    Hahn GM: Hyperthermia and Cancer. Plenum Press, New York, 1982Google Scholar
  183. 182.
    Jain RK, Gullino PM (eds): Thermal Characteristics of Tumors: Applications in Detection and Treatment. Annals of the New York Academy of Sciences 335, 1980Google Scholar
  184. 183.
    Sevitt S: Early and delayed edema and increases in capillary permeability after burns of the skin. J Pathol Bact 75: 27–37, 1958Google Scholar
  185. 184.
    Wilhelm DL, Mason B: Vascular permeability changes in inflammation: The role of endogenous permeability factors in mild thermal injury. Br J Exp Pathol 61: 487–506, 1960Google Scholar
  186. 185.
    Cotran RS, Remensnyder JP: The structural basis of increased vascular permeability after graded thermal injury - light and electron microscopic studies. Ann N.Y. Acad Sci 150: 495–509, 1968Google Scholar
  187. 186.
    Arturson G: Microvascular permeability to macromolecules in thermal injury. Acta Physiol Scand Suppl 463: 111–112, 1979Google Scholar
  188. 187.
    Ackerman NB, Makohon S: The effects of cooling, freezing, and thawing on vascular permeability and perfusion in experimental liver metastases. Surg Gynec Obstet 152: 262–267, 1981Google Scholar
  189. 188.
    Lefor AT, Makohon S, Ackerman NB: The effects of hyperthermia on vascular permeability in experimental liver metastasis. J Surg Oncol 28: 297–300, 1981Google Scholar
  190. 189.
    Gerlowski LE, Jain RK: Effect of hyperthermia on microvascular permeability of normal and neoplastic tissues. Intl J Microcirc: Clinical and Expt 4: 336–372, 1985Google Scholar
  191. 190.
    Svensjö E, Joyner WL: The effects of intermittant and continuous stimulation of microvessels in the cheek pouch of hamsters with histamine and bradykinin on the development of venular leaky sites. J Microcirc Endothel Lymphat 1: 381, 1984Google Scholar
  192. 191.
    Senger DR, Galli SJ, Dvorak AM, Peruzzi CA, Harvery VS, Dvorak HF: Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219: 983–985, 1983Google Scholar
  193. 192.
    Senger DR, Peruzzi CA, Feder J, Dvorak HF: A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines. Cancer Res 46: 5629–5632, 1986Google Scholar
  194. 193.
    Ackerman NB, Hechmer PA, Makohon S: Failure of histamine type mediators to enhance vascular permeability in experimental liver metastasis. Surg Gynec Obstet 151: 647–651, 1980Google Scholar
  195. 194.
    Jain RK, Shah SA, Finney PL: Continuous non-invasive monitoring of pH and temperature in rat Walker 256 carcinoma during normo-and hyperglycemia. J Natl Cancer Inst 73: 429–436, 1984Google Scholar
  196. 195.
    Ward-Hartley K, Jain RK: Effect of glucose and galactose on microcirculatory flow in normal and neoplastic tissues in rabbits. Cancer Res 47: 371–377, 1987Google Scholar
  197. 196.
    Ward KA, Jain RK: Physiological response on tumors to hyperglycemia: Characterization, significance, and role in hyperthermia. International Journal of Hyperthermia, (in press)Google Scholar

Copyright information

© Martinus Nijhoff Publishers 1987

Authors and Affiliations

  • Rakesh K. Jain
    • 1
  1. 1.Department of Chemical EngineeringCarnegie Mellon UniversityPittsburghUSA

Personalised recommendations