This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Less, J. R. Articles by Jain, R. K. Search for Related Content PubMed PubMed Citation Articles by Less, J. R. Articles by Jain, R. K.

Interstitial Hypertension in Human Breast and Colorectal Tumors¹

Departments of Surgery [J. R. L., M. C. P., N. W.] and Pathology [D. B.], University of Pittsburgh, and Department of Chemical Engineering, Carnegie Mellon University [J. R. L., Y. B., R. K. J.], Pittsburgh, Pennsylvania 15213

The efficacy of present day antineoplastic regimens depends upon the delivery and penetration of therapeutic agents through the tumor vascular and interstitial spaces to the tumor cell target. The distribution of relevant molecules or cells in a solid tumor is often poor and heterogeneous and is believed to be due to a number of pathophysiological factors, including elevated interstitial fluid pressure (IFP). Using the wick-in-needle technique, IFP was measured in primary breast and colorectal carcinomas as well as their respective metastases to the lymph nodes and liver in a total of 17 patients. IFP was also measured in one recurrent renal cell carcinoma, one melanoma metastasis to the lymph nodes, and another melanoma metastasis to the lung. IFP varied from 4 to 50 mm Hg with a mean ± SD of 20 ± 13 mm Hg in the neoplasms (n = 41 measurements; n = 21 tumors), while IFP in normal tissues had a mean of 2 ± 4 mm Hg (n = 11). The mean IFPs for metastatic melanoma, primary breast carcinoma, and liver metastases from a colorectal primary were found to be 33 ± 14, 15 ± 9, and 21 ± 12 mm Hg, respectively. In the renal cell carcinoma, the pressure was 38 mm Hg. These results agree with the findings of our 3 previous studies examining IFP in human superficial melanomas (14.3 ± 12.5 mm Hg, n = 12), cervical carcinomas (15.7 ± 5.7 mm Hg, n = 12), and head and neck tumors (13.2 ± 8.8 mm Hg, n = 19), and indicate that in all types of human tumors studied to date, IFP was significantly elevated above that of normal tissue. This observation may be useful in localizing tumors during needle biopsy.

¹ This work was supported by grants from the American Cancer Society (J. R. L.) and National Cancer Institute (R. K. J.), and by a Humboldt Senior Scientist Award (R. K. J.). This is the fourth paper in a series on interstitial hypertension in human tumors. Preliminary reports of this work were presented at the Angiogenesis Symposium in St. Gallen, Switzerland, March 1991; American Association for Cancer Research Meeting, Houston, TX, May 1991; the Ninth International Congress for Radiation Research, Toronto, Canada, July 1991; and the Fifth World Congress for Microcirculation, Louisville, KY, September 1991.

² Present address: USFDA, Office of Device Evaluation, 1390 Piccard Drive, Rockville, MD 20850. The opinions and statements expressed in this report are those of the authors and may not reflect the views of the Department of Health and Human Services (DHHS).

³ Present address: Steele Laboratory, Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114.

⁴ To whom requests for reprints should be addressed.

Received 7/ 2/92. Accepted 9/ 9/92.

This article has been cited by other articles:

				V. Gioni, T. Karampinas, G. Voutsinas, A. E. Roussidis, S. Papadopoulos, N. K. Karamanos, and D. Kletsas Imatinib Mesylate Inhibits Proliferation and Exerts an Antifibrotic Effect in Human Breast Stroma Fibroblasts Mol. Cancer Res., May 1, 2008; 6(5): 706 - 714. [Abstract] [Full Text] [PDF]

				D. H. Craig, B. Haimovich, and M. D. Basson {alpha}-Actinin-1 phosphorylation modulates pressure-induced colon cancer cell adhesion through regulation of focal adhesion kinase-Src interaction Am J Physiol Cell Physiol, December 1, 2007; 293(6): C1862 - C1874. [Abstract] [Full Text] [PDF]

				T.-Y. Lee, C.-T. Lin, S.-Y. Kuo, D.-K. Chang, and H.-C. Wu Peptide-Mediated Targeting to Tumor Blood Vessels of Lung Cancer for Drug Delivery Cancer Res., November 15, 2007; 67(22): 10958 - 10965. [Abstract] [Full Text] [PDF]

				K. Hayashi, P. Jiang, K. Yamauchi, N. Yamamoto, H. Tsuchiya, K. Tomita, A.R. Moossa, M. Bouvet, and R. M. Hoffman Real-time Imaging of Tumor-Cell Shedding and Trafficking in Lymphatic Channels Cancer Res., September 1, 2007; 67(17): 8223 - 8228. [Abstract] [Full Text] [PDF]

				Y. Hassid, E. Furman-Haran, R. Margalit, R. Eilam, and H. Degani Noninvasive magnetic resonance imaging of transport and interstitial fluid pressure in ectopic human lung tumors. Cancer Res., April 15, 2006; 66(8): 4159 - 4166. [Abstract] [Full Text] [PDF]

				J. V. Skliarenko, S. J. Lunt, M. L. Gordon, A. Vitkin, M. Milosevic, and R. P. Hill Effects of the Vascular Disrupting Agent ZD6126 on Interstitial Fluid Pressure and Cell Survival in Tumors Cancer Res., February 15, 2006; 66(4): 2074 - 2080. [Abstract] [Full Text] [PDF]

				R. Cairns, I. Papandreou, and N. Denko Overcoming Physiologic Barriers to Cancer Treatment by Molecularly Targeting the Tumor Microenvironment Mol. Cancer Res., February 1, 2006; 4(2): 61 - 70. [Abstract] [Full Text] [PDF]

				M. Dadiani, R. Margalit, N. Sela, and H. Degani High-Resolution Magnetic Resonance Imaging of Disparities in the Transcapillary Transfer Rates in Orthotopically Inoculated Invasive Breast Tumors Cancer Res., May 1, 2004; 64(9): 3155 - 3161. [Abstract] [Full Text] [PDF]

				M. Vavra, M. J. Ali, E. W.-Y. Kang, Y. Navalitloha, A. Ebert, C. V. Allen, and D. R. Groothuis Comparative pharmacokinetics of 14C-sucrose in RG-2 rat gliomas after intravenous and convection-enhanced delivery Neuro-oncol, April 1, 2004; 6(2): 104 - 112. [Abstract] [PDF]

				K. Pietras, K. Rubin, T. Sjoblom, E. Buchdunger, M. Sjoquist, C.-H. Heldin, and A. Ostman Inhibition of PDGF Receptor Signaling in Tumor Stroma Enhances Antitumor Effect of Chemotherapy Cancer Res., October 1, 2002; 62(19): 5476 - 5484. [Abstract] [Full Text] [PDF]

				E. K. Rofstad, S. H. Tunheim, B. Mathiesen, B. A. Graff, E. F. Halsor, K. Nilsen, and K. Galappathi Pulmonary and Lymph Node Metastasis Is Associated with Primary Tumor Interstitial Fluid Pressure in Human Melanoma Xenografts Cancer Res., February 1, 2002; 62(3): 661 - 664. [Abstract] [Full Text] [PDF]

				M. Milosevic, A. Fyles, D. Hedley, M. Pintilie, W. Levin, L. Manchul, and R. Hill Interstitial Fluid Pressure Predicts Survival in Patients with Cervix Cancer Independent of Clinical Prognostic Factors and Tumor Oxygen Measurements Cancer Res., September 1, 2001; 61(17): 6400 - 6405. [Abstract] [Full Text] [PDF]

				P. A. Netti, L. M. Hamberg, J. W. Babich, D. Kierstead, W. Graham, G. J. Hunter, G. L. Wolf, A. Fischman, Y. Boucher, and R. K. Jain Enhancement of fluid filtration across tumor vessels: Implication for delivery of macromolecules PNAS, March 16, 1999; 96(6): 3137 - 3142. [Abstract] [Full Text] [PDF]