Summary
This review describes some aspects of tumor vessels and the influence of vasoactive agents on tumor blood flow, particularly the characteristic microcirculation of tumors with regard to its selective increase in blood flow. Elevation of blood pressure by infusion of angiotensin II produced a severalfold increase in tumor blood flow. The increase was selective and specific to the tumor vessels as long as the mean arterial blood pressure was kept under 150 mm Hg. Pressure elevation by angiotensin II also selectively increased tumor oxygen tension and influx of lymph flow from the primary transplanted lesion to the lymph node metastatic lesion. Newly devised techniques for analyzing microhemodynamics of tumor vessels showed that the velocity of tumor blood flow, the vascular area in tumor tissue, and the hydrostatic pressure difference between the tumor vessel and extravascular tissue were markedly enhanced. Thus, the extravasation of material into tumor tissues can be increased by the enhancement of blood flow. This demonstration allowed the development of a new approach to cancer chemotherapy, in which the delivery to tumor tissue of systemically administered anticancer drugs can be selectively enhanced.
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Greene HSN: Heterologous transplantation of mammalian tumors. I. The transfer of rabbit tumors to alien species. J Exp Med 73: 461–474, 1941.
Gimbrone MAJr, Leapman SB, Cotran RS, Folkman J: Tumor dormancy in vivo by prevention of neovascularization. J Exp Med 136: 261–276, 1972.
Folkman J: Tumor angiogenesis factor. Cancer Res 34: 2109–2113, 1974.
Suzuki M, Abe I, Hori K, Saito S, Sato H: Characteristic blood circulation in tumor tissue, with reference to local permeation of drug in cancer chemotherapy. In: Proceedings of the 36th annual meeting of the Japanese Cancer Association, Tokyo. Tokyo: Japanese Cancer Association, 1977, p 149.
Suzuki M, Hori K, Abe I, Saito H: Characteristics of microcirculation in tumor. Jpn J Cancer Chemother 6 (Suppl II): 287–291, 1979.
Suzuki M, Hori K, Abe I, Saito S, Sato H: Characteristic microcirculation of tumor. J Jap Coll Angiol 19: 233–236, 1979.
Suzuki M, Hori K, Abe I, Saito S, Sato H: Experimental study on characteristics of microcirculation in tumor tissue, with reference to cancer chemotherapy. In: Hellmann K, Hilgard P, Eccles S (eds) Metastasis: Clinical and Experimental Aspects. Martinus Nijhoff, The Hague, 1980, pp 356–360.
Suzuki M, Hori K, Abe I, Saito S, Sato H: A new approach to cancer chemotherapy: Selective enhancement of tumor blood flow with angiotensin II. J Natl Cancer Inst 67: 663–669, 1981.
Sato H, Suzuki M: Difference and agreement between the primary lesion and metastasis of cancer, with reference to the stroma of the tumor. Jpn J Clin Oncol 11 (Suppl): 159–166, 1981.
Suzuki M, Hori K, Abe I, Saito S, Sato S: Functional characteristic of tumor vessels, with reference to enhancement of the drug delivery. Jap J Cancer Clin 28: 592–598, 1982.
Suzuki M, Hori K, Abe I, Saito S, Sato H: Microcirculation of tumor concerning cancer chemotherapy. Tohoku Igaku Z 94: 44–46, 1981.
Hori K, Suzuki M, Abe I, Saito S, Sato H: New technique for measurement of microvascular pressure in normal and tumor vessels of rats. Invasion Metastasis 1: 248–260, 1981.
Hori K, Suzuki M, Abe I, Saito S, Sato H: Increase in tumor microvascular pressure by angiotensin-induced hypertension: Implication for pharmacokinetic analysis of drug delivery into tumor tissue. Jpn J Cancer Chemother 10: 953–960, 1983.
Sato H, Sato K, Sato Y, Mimata Y, Asamura M, Kanamaru R, Wakui A, Suzuki M, Sato H: Clinical study on selective enhancement of drug delivery by angiotensin II in cancer chemotherapy. In: Hellmann K, Hilgard P, Eccles S (eds) Metastasis: Clinical and Experimental Aspects. Martinus Nijhof, The Hague, 1980, pp 388–394.
Sato H, Sato K, Sato Y, Asamura M, Kanamaru R, Sugiyama Z, Kitahara T, Mimata Y, Wakui A, Suzuki M, Hori K, Abe I, Saito S, Sato H: Induced hypertension chemotherapy of cancer patients by selective enhancement of drug delivery to tumor tissue with angiotensin II. Sci Rep Res Inst Tohoku Univ-C 28: 32–44, 1981.
Wakui A, Suzuki M: Cancer chemotherapy in combination with angiotensin-induced hypertension. Jpn J Cancer Chemother 10: 1577–1583, 1983.
Ide AG, Baker NH, Warren SL: Vascularization of the Brown-Pearce rabbit epithelioma transplant as seen in the transparent ear chamber. Am J Roentgenol 42: 891–899, 1939.
Algire GH, Chalkely HW, Legallais FY, Park HD: Vascular reactions of normal and malignant tissues in vivo. 1. Vascular reactions of mice to wounds and to normal and neoplastic transplants. J Natl Cancer Inst 6: 73–85, 1945.
Greenblatt M, Shubik P: Tumor angiogenesis. Transfilter diffusion studies in the hamster by the transparent chamber technique. J Natl Cancer Inst 41: 111–124, 1968.
Cavallo T, Sade R, Folkman J, Cotran RS: Tumor angiogenesis. Rapid induction of endothelial mitoses demonstrated by autoradiography. J Cell Biol 54: 408–420, 1972.
Folkman J: tumor angiotenesis. Therapeutic implications. N Eng J Med 285: 1182–1186, 1971.
Folkman J, Merler E, Abernathy C, Williams G: Isolation of a tumor factor responsible for angiotenesis. J Exp Med 133: 275–288, 1971.
Ziche M, Jones J, Gullino PM: Role of prostaglandin E1 and copper in angiogenesis. J Natl Cancer Inst 69: 475–482, 1982.
Yamaura H, Sato H: Quantitative studies on the developing vascular system of the hepatoma. J Natl Cancer Inst 53: 1229–1240, 1974.
Warren BA, Shubik P: The growth of the blood supply to melanoma transplants in the hamster cheek pouch. Lab Invest 15: 464–478, 1966.
Muthukkarppan VR, Kubai L, Auerback R: Tumor-induced neovascularization in the mouse eye. J Natl Cancer Inst 69: 699–708, 1982.
Gimbrone MA, Cotran RS, Leapman SB, Folkman J: Tumor growth and neovascularization. An experimental model using the rabbit cornea. J Natl Cancer Inst 52: 413–427, 1974.
Warren BA: The ultrastructure of the microcirculation at the advancing edge of Walker 256 carcinoma. Microvasc Res 2: 443–453, 1970.
Eddy HA, Casarett W: Development of vascular system in the hamster malignant neurilemmoma. Microvasc Res 6: 63–82, 1973.
Reinhold HS: Improved microcirculation in irradiated tumors. Eur J Cancer 7: 273–280, 1971.
Kjartansson I: Tumour circulation. An experimental study in the rat with a comparison of different methods for estimation of tumour blood flow. Acta Chir Scand Suppl 471: 1–74, 1976.
Endrich B, Reinhold HS, Gross JF, Intaglietta M: Tissue perfusion inhomogeneity during early tumor growth in rats. J Natl Cancer Inst 62: 387–395, 1979.
Peterson H-I: Tumor blood flow compared with normal tissue blood flow. In: Peterson H-I (ed) Tumor blood flow. CRC Press. Florida, 1979, pp 103–114.
Thomlinson RH, Gray LH: The histological structure of some human lung cancers and the possible implications for radiotherapy. Brit J Cancer 9: 539–549, 1955.
Warren BA: The vascular morphology of tumors. In: Peterson H-I (ed) Tumor blood flow. CRC Press, Florida, 1979, pp 1–47.
Krylova NV: Characteristics of microcirculation in experimental tumors. Bibl Anat 10: 301–303, 1969.
Kligerman MM, Henel DK: Some aspects of the microcirculation of a transplantable experimental tumor. Radiology 76: 810–817, 1961.
Gullino PM, Grantham FH: Studies on the exchange of fluids between host and tumor. III. Regulation of blood flow in hepatomas and other rat tumors. J Natl Cancer Inst 28: 211–229, 1962.
Cater DB, Adair HM, Grove CA: Effects of vasomotor drugs and ‘mediators’ of the inflammatory reaction upon the oxygen tension of tumours and tumour blood-flow. Br J Cancer 20: 504–516, 1966.
Edlich RF, Rogers W, DeShazo CVJr, Aust JB: Effect of vasoactive drugs on tissue blood flow in the hamster melanoma. Cancer Res 26: 1420–1424, 1966.
Rankin JH, Jirtle R, Phernetton TM: Anomalous responses of tumor vasculature to norepinephrine and prostaglandin E2 in the rabbit. Circ Res 41: 496–502, 1977.
Kruuv JA, Inch WR, McCredie JA: Blood flow and oxygenation of tumors in mice. II. Effects of vasodilator drugs. Cancer 20: 60–65, 1967.
Wickersham JK, Barrett WP, Furukawa SB, Puffer HW, Warner NE: An evaluation of the response of the microvasculature in tumors in C3H mice to vasoactive drugs. Bibl Anat 15: 291–293, 1977.
Ackerman NB, Hechmer PA: Effects of phamacological agents on the microcirculation of tumors implanted in the liver. Bibl Anat 15: 301–303, 1977.
Mattson J, Appelgren L, Karlsson L, Peterson HI: Influence of vasoactive drugs and ischaemia on intra-tumour blood flow distribution. Eur J Cancer 14: 761–764, 1978.
Jirtle R, Clifton KH, Rankin JHG: Effects of several vasoactive drugs on the vascular resistance of MT-W9B tumors in W/Fu rats. Cancer Res 38: 2385–2390, 1978.
Young SW, Hollenberg NK, Kazam E, Berkowitz DM, Hainen R, Sandor T, Abrams HL: Resting host and tumor perfusion as determinants of tumor vascular responses to norepinephrine. Cancer Res 39: 1898–1903, 1979.
Takács L, Debreczeni LA, Farsang Cs: Regional vascular reactivity in rats with Guerin carcinoma (GC). Experientia 35: 1238–1240, 1979.
Hafström L, Nobin A, Persson B, Sundqvist K: Effects of catecholamines on cardiovascular response and blood flow distribution to normal tissue and liver tumors in rats. Cancer Res 40: 481–485, 1980.
Kaelin WGJr, Shrivasta S, Shand DG, Jirtle RL: Effect of verapamil on malignant tissue blood flow in SMT-2A tumor-bearing rats. Cancer Res 42: 3944–3949, 1982.
Mattson J, Peterson H-I: Influence of vasoactive drugs on tumour blood flow (Review). Anticancer Res 1: 59–61. 1981.
Young SW, Muller HH, Marincek B: Response of neoplastic and normal vasculature to acetylcholine. Eur J Cancer Clin Oncol 9: 383–387, 1983.
Häggendal E, Johansson B: On the pathophysiology of the increased cerebrovascular permeability in acute arterial hypertension in cats. Acta Neurol Scand 48: 265–270, 1972.
Suzuki T, Tominaga S, Strandgaard S, Nakamura T: Fluorescein cineangiography of the pial microcirculation in the rat in acute angiotensin-induced hypertension. In: Harper M, Jennett B, Miller D, Rowan J (eds) Blood flow and metabolism in the brain. Churchill-Livingstone, Edinburgh, 1975, pp 5.8–5.9.
MacKenzie ET, Strandgaard S, Graham DI, Jones JV, Harper AM, Farrar JK: Effects of acutely induced hypertension in cats on pial arteriolar caliber, local cerebral blood flow, and the blood-brain barrier. Circ Res 39: 33–41, 1976.
Suzuki M, Abe I, Sato H: Changes in drug delivery (by blood-brain barrier dysfunction) on arachnoid leukemia: implication for CNS leukemic dissemination. Clin Expl Metastasis 1: 163–171, 1983.
Semple SJG, de Wardener HE: Effect of increased renal venous pressure on circulatory ‘autoregulation’ of isolated dog kidneys. Circ Res 7: 643–648, 1959.
Algire GH, Legallais FY, Anderson BF: Vascular reaction of normal and malignant tissues in vivo. VI. The role of hypotension in the action of components of podophyllin on transplanted sarcomas. J Natl Cancer Inst 14: 879–893, 1954.
Gullino PM, Grantham PH: Studies on the exchange of fluides between host and tumor. II. The blood flow of hepatomas and other tumors in rats and mice. J Natl Cancer Inst 27: 1465–1491, 1961.
Rogers W, Edlich RF, Lewis DV, Aust JB: Tumor blood flow. I. Blood flow in transplantable tumors during growth. Surg Clin N America 47: 1473–1482, 1967.
Cataland S, Cohen C, Sapirstein LA: Relationship between size and perfusion rate of transplanted tumors. J Natl Cancer Inst 29: 389–394, 1962.
Vaupel P: Interrelationship between mean arterial blood pressure, blood flow, and vascular resistance in solid tumor tissue of DS-Carcinosarcoma. Experienta 31: 587–589, 1975.
Edlich RF, Borner J, Buchin RJ: Microcirculation of tumor Influence of implantation site on tumor blood flow. Arch Surg 98: 233–234, 1969.
Young SW, Hollenberg NK, Abrams HL: The influence of implantation site on tumor growth and blood flow. Eur J Cancer 15: 771–777, 1979.
Endrich B, Intaglietta M, Reinhold HS, Gross JF: Hemodynamic characteristics in microcirculatory blood channels during early tumor growth. Cancer Res 39: 17–23, 1979.
Hori K, Suzuki M, Abe I, Saito S, Sato H: A micro-occlusion technique for measurement of the microvascular pressure in tumor and subcutis. Gann 74: 122–127, 1983.
Peters W, Teixeira M, Intaglietta M, Gross JF: Microcirculatory studies in rat mammary carcinoma. I. Transparent chamber method, development of microvasculature, and pressures in tumor vessels. J Natl Cancer Inst 65: 631–642, 1980.
Butler TP, Grantham FH, Gullino PM: Bulk transfer of fluid in the interstitial component of mammay tumors. Cancer Res 35: 3084–3088, 1975.
Hori K, Suzuki M, Abe I, Saito S, Sato H: Change in pressure difference between intra- and extravascular space in tumor tissue by angiotensin-induced hypertension. In: Proceedings of the 41st annual meeting of the Japanese Cancer Association, Osaka. Japanese Cancer Association, Tokyo, 1982, p 234.
Suzuki M, Hori K, Abe I, Saito S, Sato H: Characteristics of microcirculation in methylcholanthrene-induced primary tumors and in lymphnode metastasis. In: Proceedings of the 38th annual meeting of the Japanese Cancer Association, Tokyo, Japenese Cancer Association, Tokyo, 1979, p 298.
Gray LH, Conger AD, Ebert M, Hornsey S, Scott OCA: The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol 26: 638–648, 1953.
Vaupel P: Hypoxia in neoplastic tissue. Microvasc Res 13: 399–408, 1977.
Suzuki M, Hori K, Abe I, Saito S, Sato H: Selective increase in tumor oxygen tension with angiotensin II. Invasion Metastasis 2: 33–39, 1982.
Ichimura H: Experimental studies on a screening system of anticancer drugs employing the rat ascites hepatoma spectrum. Jpn J Cancer Chemother 2: 605–610, 1975.
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Suzuki, M., Hori, K., Abe, I. et al. Functional characterization of the microcirculation in tumors. Cancer Metast Rev 3, 115–126 (1984). https://doi.org/10.1007/BF00047659
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DOI: https://doi.org/10.1007/BF00047659