PMID- 2736517 OWN - NLM STAT- MEDLINE DCOM- 19890803 LR - 20131121 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 49 IP - 14 DP - 1989 Jul 15 TI - Blood flow, metabolism, cellular microenvironment, and growth rate of human tumor xenografts. PG - 3759-64 AB - Better understanding of the micromilieu of human tumors in situ is mandatory for further improvement of diagnostic and therapeutic interventions. Since investigations of untreated tumors of a wide size range are precluded in humans for ethical reasons, size-dependent changes in the pathophysiology of primary and metastatic human tumors were studied using "tissue-isolated" xenografts in nude rats. Tumor types included lung and breast cancers, ovarian and thyroid carcinomas, uterus tumors, and melanomas. A 10-fold variation in weight-adjusted tumor perfusion indicated large variations in angiogenesis which were unrelated to tumor type. Flow values obtained were consistent with data from clinical observations and were comparable to that in isografted rodent tumors. Using actual consumption and supply rates, maximum oxygen and glucose uptake rates were calculated for each tumor type. The capacity to consume oxygen and glucose varied 9-fold and 4-fold, respectively. However, considering actual consumption rates, blood flow was the principal modulator of substrate supply and tumor metabolism in these human tumor xenografts. Consequently, therapeutically relevant parameters of the metabolic micromilieu largely depended on the efficacy of the tumor circulation. Hereby, high metabolic rates concomitant with high flow values coincided with rapid tumor growth. Thus, in order to design the best individualized therapy, flow-related data should supplement histological classification and clinical staging and grading. Further development of relatively noninvasive technologies (magnetic resonance imaging, magnetic resonance spectroscopy, or positron emission tomography) might permit such monitoring. FAU - Kallinowski, F AU - Kallinowski F AD - Department of Radiation Medicine, Massachusetts General Hospital, Harvard Medical School, Boston 02114. FAU - Schlenger, K H AU - Schlenger KH FAU - Runkel, S AU - Runkel S FAU - Kloes, M AU - Kloes M FAU - Stohrer, M AU - Stohrer M FAU - Okunieff, P AU - Okunieff P FAU - Vaupel, P AU - Vaupel P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (Lactates) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Carcinosarcoma/physiopathology MH - Female MH - Glucose/metabolism MH - Humans MH - Lactates/metabolism MH - Mice MH - Mice, Nude MH - Neoplasm Transplantation MH - Neoplasms, Experimental/blood supply/metabolism/pathology/*physiopathology MH - Ovarian Neoplasms/physiopathology MH - Oxygen Consumption MH - Rats MH - Rats, Inbred Strains MH - Regional Blood Flow MH - Transplantation, Heterologous EDAT- 1989/07/15 00:00 MHDA- 1989/07/15 00:01 CRDT- 1989/07/15 00:00 PHST- 1989/07/15 00:00 [pubmed] PHST- 1989/07/15 00:01 [medline] PHST- 1989/07/15 00:00 [entrez] PST - ppublish SO - Cancer Res. 1989 Jul 15;49(14):3759-64.