PMID- 9426072
OWN - NLM
STAT- MEDLINE
DCOM- 19980120
LR  - 20141120
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 58
IP  - 1
DP  - 1998 Jan 1
TI  - Modulation of enhanced vascular permeability in tumors by a bradykinin 
      antagonist, a cyclooxygenase inhibitor, and a nitric oxide scavenger.
PG  - 159-65
AB  - The mechanism of the enhanced vascular permeability and retention (EPR) effect 
      seen in solid tumors was investigated with sarcoma 180 (S-180) in mice by using 
      the bradykinin receptor antagonist D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin] (HOE 
      140), the nitric oxide (NO) scavenger 
      2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), and the 
      cyclooxygenase (prostaglandin synthase) inhibitor indomethacin. In the S-180 
      solid tumor model, administration of HOE 140 (0.65 or 1.3 microg/kg/8 h, s.c.), 
      PTIO (167 mg/kg/2 h, four times/8 h, i.p.), or indomethacin (5 or 10 mg/kg/day, 
      three times, i.p.) significantly suppressed the EPR effect in the tumor, and the 
      combined administration of these agents achieved a stronger inhibition of the EPR 
      effect than did each compound alone. Indomethacin (10 mg/kg/day, three times) 
      plus PTIO (167 mg/kg/2 h, four times) given i.p. had the greatest inhibition 
      (70%) on the EPR effect. When HOE 140 was administered s.c. at a dose of 13 
      microg/kg/12 h for 2 weeks after tumor inoculation, growth of the solid tumor was 
      also suppressed by 32%, by tumor weight. In the ascitic form of S-180, i.p. 
      administration of HOE 140 at 13 microg/kg/12 h initiated immediately after tumor 
      inoculation significantly suppressed formation of S-180 tumor ascites; the life 
      span of ascitic S-180 tumor-bearing mice was prolonged at the same dose of HOE 
      140. The expression of inducible NO synthase mRNA and of cyclooxygenase 2 mRNA in 
      S-180 tumor tissue was highly elevated, as evidenced by Northern blotting and 
      reverse transcription-PCR and by Southern blot analyses. These results indicate 
      that bradykinin, NO, and prostaglandins play an important role in enhanced 
      vascular permeability in tumor tissue and sustain tumor growth. More importantly, 
      bradykinin antagonists such as HOE 140 may be beneficial for the inhibition of 
      tumor growth.
FAU - Wu, J
AU  - Wu J
AD  - Department of Microbiology, Kumamoto University School of Medicine, Japan.
FAU - Akaike, T
AU  - Akaike T
FAU - Maeda, H
AU  - Maeda H
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 (Bradykinin Receptor Antagonists)
RN  - 0 (Cyclic N-Oxides)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Imidazoles)
RN  - 18390-00-6 (2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 7PG89G35Q7 (icatibant)
RN  - 94ZLA3W45F (Arginine)
RN  - S8TIM42R2W (Bradykinin)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - Animals
MH  - Arginine/pharmacology
MH  - Ascites/prevention & control
MH  - Bradykinin/*analogs & derivatives/pharmacology/physiology
MH  - *Bradykinin Receptor Antagonists
MH  - Capillary Permeability/*drug effects/physiology
MH  - Cyclic N-Oxides/*pharmacology
MH  - Cyclooxygenase Inhibitors/*pharmacology
MH  - Free Radical Scavengers/*pharmacology
MH  - Imidazoles/*pharmacology
MH  - Indomethacin/*pharmacology
MH  - Male
MH  - Mice
MH  - Neoplasms, Experimental/*blood supply/metabolism
MH  - Nitric Oxide/antagonists & inhibitors
MH  - Sarcoma 180/blood supply/metabolism
EDAT- 1998/01/13 00:00
MHDA- 1998/01/13 00:01
CRDT- 1998/01/13 00:00
PHST- 1998/01/13 00:00 [pubmed]
PHST- 1998/01/13 00:01 [medline]
PHST- 1998/01/13 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1998 Jan 1;58(1):159-65.