PMID- 9539785
OWN - NLM
STAT- MEDLINE
DCOM- 19980513
LR  - 20220409
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 95
IP  - 8
DP  - 1998 Apr 14
TI  - Regulation of transport pathways in tumor vessels: role of tumor type and 
      microenvironment.
PG  - 4607-12
AB  - Novel anti-neoplastic agents such as gene targeting vectors and encapsulated 
      carriers are quite large (approximately 100-300 nm in diameter). An understanding 
      of the functional size and physiological regulation of transvascular pathways is 
      necessary to optimize delivery of these agents. Here we analyze the functional 
      limits of transvascular transport and its modulation by the microenvironment. One 
      human and five murine tumors including mammary and colorectal carcinomas, 
      hepatoma, glioma, and sarcoma were implanted in the dorsal skin-fold chamber or 
      cranial window, and the pore cutoff size, a functional measure of transvascular 
      gap size, was determined. The microenvironment was modulated: (i) spatially, by 
      growing tumors in subcutaneous or cranial locations and (ii) temporally, by 
      inducing vascular regression in hormone-dependent tumors. Tumors grown 
      subcutaneously exhibited a characteristic pore cutoff size ranging from 200 nm to 
      1.2 microm. This pore cutoff size was reduced in tumors grown in the cranium or 
      in regressing tumors after hormone withdrawal. Vessels induced in basic 
      fibroblast growth factor-containing gels had a pore cutoff size of 200 nm. 
      Albumin permeability was independent of pore cutoff size. These results have 
      three major implications for the delivery of therapeutic agents: (i) delivery may 
      be less efficient in cranial tumors than in subcutaneous tumors, (ii) delivery 
      may be reduced during tumor regression induced by hormonal ablation, and (iii) 
      permeability to a molecule is independent of pore cutoff size as long as the 
      diameter of the molecule is much less than the pore diameter.
FAU - Hobbs, S K
AU  - Hobbs SK
AD  - Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts 
      General Hospital and Harvard Medical School, 100 Blossom St., Cox-7, Boston, MA 
      02114, USA.
FAU - Monsky, W L
AU  - Monsky WL
FAU - Yuan, F
AU  - Yuan F
FAU - Roberts, W G
AU  - Roberts WG
FAU - Griffith, L
AU  - Griffith L
FAU - Torchilin, V P
AU  - Torchilin VP
FAU - Jain, R K
AU  - Jain RK
LA  - eng
GR  - R35-CA56591/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Liposomes)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
SB  - IM
MH  - Adenocarcinoma/blood supply/pathology/therapy
MH  - Animals
MH  - Colonic Neoplasms/blood supply/pathology/therapy
MH  - Fibroblast Growth Factor 2/pharmacology
MH  - Humans
MH  - Liposomes
MH  - Male
MH  - Mice
MH  - Microcirculation/*pathology/ultrastructure
MH  - Microspheres
MH  - Neoplasms, Experimental/*blood supply/*pathology/therapy/ultrastructure
MH  - Neovascularization, Pathologic/chemically induced/pathology/*prevention & control
MH  - Orchiectomy
PMC - PMC22537
EDAT- 1998/05/16 00:00
MHDA- 1998/05/16 00:01
PMCR- 1998/10/14
CRDT- 1998/05/16 00:00
PHST- 1998/05/16 00:00 [pubmed]
PHST- 1998/05/16 00:01 [medline]
PHST- 1998/05/16 00:00 [entrez]
PHST- 1998/10/14 00:00 [pmc-release]
AID - 4134 [pii]
AID - 10.1073/pnas.95.8.4607 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4607-12. doi: 10.1073/pnas.95.8.4607.