==================================BSR38==================================
38. Experimental neovascularization of rat cornea.
This is one model of neovascularization of the
ocular tissue (retina, iris, cornea).
1
UI - 87048875
AU - Polverini PJ ; Novak RF
TI - Inhibition of angiogenesis by the antineoplastic agents mitoxantrone and
bisantrene.
AB - The effects of mitoxantrone and bisantrene on angiogenic responses
induced by tumor cell-conditioned media in the avascular cornea of rat
eye have been evaluated. Both mitoxantrone and bisantrene effectively
inhibited, in a concentration-dependent manner, angiogenesis induced by
conditioned media obtained from either a hamster buccal pouch carcinoma
cell line or P388D1 murine macrophage-like cells. Whereas vessel ingrowth
in corneas containing tumor cell-conditioned media was detected as early
as day 2 or 3 and was maximal by day 7, inclusion of mitoxantrone or
bisantrene in the conditioned media at a 1:1 ratio (160 microM
mitoxantrone or 32 microM bisantrene) resulted in complete inhibition of
angiogenesis throughout the 14-day evaluation period. When concentrations
of 64 and 32 microM mitoxantrone or 13 and 6.4 microM bisantrene were
employed there was a marked delay in the appearance of capillary blood
vessels (day 5 to 7) and a reduction in the intensity of angiogenic
responses. No untoward toxicity to the tissue was observed at the
concentrations of mitoxantrone or bisantrene employed.
MH - Animal ; Anthracenes/PHARMACODYNAMICS ; Antineoplastic Agents/
*PHARMACODYNAMICS ; Cornea/BLOOD SUPPLY ; Culture Media ; Mitoxantrone/
*PHARMACODYNAMICS ; Neovascularization/*PHYSIOPATHOLOGY ; Rats ; Support,
Non-U.S. Gov't
SO - Biochem Biophys Res Commun 1986 Nov 14;140(3):901-7
2
UI - 87023860
AU - Leure-Dupree AE
TI - Vascularization of the rat cornea after prolonged zinc deficiency.
AB - Neovascularization of the anterior stroma of the rat cornea was
associated with prolonged zinc deficiency (in this model). There was also
an increase in the myelinated nerves of the cornea. Blood vessels were
not observed in the corneas of the pair-fed and ad-libitum-fed control
animals. The invading blood vessels were frequently associated with
Schwann cells and neurites. Unmyelinated nerves were observed in the
corneal stroma of all three experimental groups.
MH - Animal ; Cornea/*BLOOD SUPPLY/INNERVATION/ULTRASTRUCTURE ; Fibroblasts/
ULTRASTRUCTURE ; Male ; *Neovascularization ; Rats ; Rats, Inbred Strains
; Schwann Cells/ULTRASTRUCTURE ; Support, U.S. Gov't, P.H.S. ; Zinc/
*DEFICIENCY
SO - Anat Rec 1986 Sep;216(1):27-32
3
UI - 86277247
AU - Alessandri G ; Raju KS ; Gullino PM
TI - Interaction of gangliosides with fibronectin in the mobilization of
capillary endothelium. Possible influence on the growth of metastasis.
AB - Mobilization of the capillary endothelium is one of the first events
observed during angiogenesis, and the study of conditions that control or
influence the mobilization of the endothelium in vitro has been assumed
to offer information relevant to the understanding of angiogenesis in
vivo. In vitro mobilization of the bovine capillary endothelium was
substantially enhanced by addition of gangliosides to the culture medium.
Optimal mobilization was obtained when the endothelium incorporated the
gangliosides first and was then seeded on fibronectin anchored to
collagen type I. Preincubation of the capillary endothelium with
gangliosides, trisialoganglioside in particular, doubled the amount of
fibronectin bound to the cells and enhanced the migration about 5-fold.
'Blockage' of ganglioside binding with cholera toxin or gamma-interferon
substantially reduced migration. Rabbit corneas, treated in vivo with a
variety of angiogenesis effectors to induce neovascularization,
consistently showed an increase in sialic acid content just prior to the
time the tissue would be penetrated by the capillaries. This finding was
interpreted to indicate that an increment of the ganglioside content of
the capillary endothelial cell membranes may play a determinant role in
the mobilization of the capillary endothelium in vivo as shown here to
take place in vitro. Since the formation of a tumor from a
micrometastasis requires formation of new capillaries and highly
metastasizing tumors very frequently have high levels of sialic acid on
the cell surface, it is hypothesized that production and shedding of
gangliosides from the surface of neoplastic cells may be a factor in
promoting angiogenesis and metastatic growth.
MH - Animal ; Capillaries/DRUG EFFECTS/*METABOLISM ; Cattle ; Cell Movement/
DRUG EFFECTS ; Cornea/ANALYSIS/DRUG EFFECTS ; Endothelium/DRUG EFFECTS/
METABOLISM ; Fibronectins/PHARMACODYNAMICS/*PHYSIOLOGY ; Gangliosides/
PHARMACODYNAMICS/*PHYSIOLOGY ; Growth Substances/PHARMACODYNAMICS ;
*Neoplasm Metastasis ; *Neovascularization ; Rabbits ; Rats ; Sialic
Acids/ANALYSIS ; Support, Non-U.S. Gov't
SO - Invasion Metastasis 1986;6(3):145-65
4
UI - 86269696
AU - Oikawa T ; Matsuzawa A ; Iwaguchi T
TI - Progression from hormone dependence to autonomy and angiogenesis in mouse
mammary tumours.
AB - The transplantable pregnancy-dependent mammary tumour (TPDMT-4), the
related hormone-dependent (TPDMT-4EP) and autonomous (T4-0I320 and
T4-0I96) subline tumours, and the mammary glands from DDD mice were
compared for angiogenic activity on the rabbit cornea by tissue
implantation. The TPDMT-4EP tumour was established by serially
transplanting TPDMT-4 tumour fragments in oestradiol plus progesterone
treated mice. The T4-0I320 and T4-0I96 tumours directly derived from the
TPDMT-4 and TPDMT-4EP tumours, respectively. Angiogenic activity was
graded by macroscopic and microscopic examinations into 3 classes;
negative, partial and complete angiogenesis. These tumours were
comparable to mammary glands in activity and induced complete
angiogenesis in only 15-23% of the implants. However, when partial and
complete responses were combined as positive angiogenesis, TPDMT-4,
T4-0I320, TPDMT-4EP and T4-0I96 tumour implants were angiogenic in 25,
29, 42 and 54%, respectively. The T4-0I96 tumour was significantly more
angiogenic than the parent tumour but this was not so for the TPDMT-4EP
tumour. Spontaneous C3H mouse mammary tumours, human gliomas from nude
mice, rat Walker 256 carcinomas and rabbit VX-2 tumours induced complete
angiogenesis in 54, 63, 59 and 92% of the implants, respectively. The
results suggest that the TPDMT-4 tumour is unique in being weakly
angiogenic and able to progress toward greater autonomy with or without
augmented angiogenic activity in different conditions.
MH - Animal ; Carcinoma 256, Walker/BLOOD SUPPLY ; Cornea/BLOOD SUPPLY ;
Estradiol/PHYSIOLOGY ; Female ; Male ; Mammary Neoplasms, Experimental/
*BLOOD SUPPLY/PHYSIOPATHOLOGY ; Mice ; Mice, Inbred C3H ; Neoplasm
Transplantation ; *Neovascularization ; Pregnancy ; Progesterone/
PHYSIOLOGY ; Rabbits ; Rats ; Support, Non-U.S. Gov't
SO - Br J Cancer 1986 Jul;54(1):91-6
5
UI - 86212516
AU - Hoban BP ; Collin HB
TI - Effects of salicylate and steroid on neutrophil migration and corneal
blood vessel growth.
AB - Cauterization of the cornea results in emigration of neutrophils from the
limbal blood vessels into the corneal tissue. Blood vessel proliferation
follows, the stimulus for which is unknown. In this study, 0.1 M sodium
salicylate drops administered topically to cauterized rat corneas over a
48-h period had an inhibitory effect on the migration of neutrophils from
the limbal vessels 6 h after injury, but this was not maintained at 48 h.
After 6 days of treatment, the salicylate had no effect on vessel growth
into the cauterized rat cornea. Application of prednisolone disodium
phosphate ointment to cauterized corneas also inhibited neutrophil
migration at 6 h, but increased the extravascular neutrophils at 48 h.
After 6 days of treatment, corneal blood vessel growth was significantly
reduced. It was concluded that there is no consistent relation between
the number of extravascular neutrophils at the corneal limbus and the
extent of corneal blood vessel growth.
MH - Animal ; Cell Movement/DRUG EFFECTS ; Cornea/*BLOOD SUPPLY/DRUG EFFECTS/
*INJURIES ; Female ; Leukocyte Count ; Male ; Neovascularization ;
Neutrophils/*DRUG EFFECTS ; Prednisolone/*ANALOGS & DERIVATIVES/
PHARMACODYNAMICS ; Rats ; Rats, Inbred Strains ; Sodium Salicylate/
*PHARMACODYNAMICS ; Support, Non-U.S. Gov't
SO - Am J Optom Physiol Opt 1986 Apr;63(4):271-6
6
UI - 86087676
AU - Koch AE ; Polverini PJ ; Leibovich SJ
TI - Induction of neovascularization by activated human monocytes.
AB - Neovascularization, the process of new blood vessel growth, is an
important feature of many pathologic and physiologic processes. Monocytes
were isolated from citrated blood buffy coat of healthy adult human
donors on Ficoll-Hypaque gradients. Mononuclear cells from these
gradients were fractionated on discontinuous Percoll gradients;
monocyte-enriched fractions were isolated and assessed for angiogenic
activity in rat corneas. Freshly isolated monocytes as well as monocytes
cultured for 20 hr on fibronectin-coated collagen gels failed to
stimulate neovascularization. In contrast, adherent monocytes activated
with concanavalin A (25 micrograms/ml) or endotoxin (5 micrograms/ml) for
20 hr were found to be potently angiogenic. We conclude that peripheral
blood monocytes must be activated to acquire the ability to induce new
blood vessel growth, a process central to inflammation, wound healing,
and tumor development.
MH - Adult ; Animal ; Cell Separation ; Cells, Cultured ; Concanavalin A/
PHARMACODYNAMICS ; Cornea/BLOOD SUPPLY ; Endotoxins/PHARMACODYNAMICS ;
Fibronectins ; Human ; Macrophage Activation ; Macrophages/DRUG EFFECTS/
*PHYSIOLOGY ; Monocytes/DRUG EFFECTS/*PHYSIOLOGY ; *Neovascularization ;
Rats ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S.
SO - J Leukocyte Biol 1986 Feb;39(2):233-8