Search PubMed⌕ Search

Biomedical subjects

J Folkman

Publications and source records attributed to J Folkman.

At least 271 records · Page 15Linked to original sources
PubMed1976

Tumor angiogenesis activity in cells grown in tissue culture.

Normal, viral transformed and tumor-derived cells grown in tissue culture and representing different species were tested for their ability to produce an extracellular tumor angiogenesis factor (TAF). TAF was assayed by measuring the host-mediated vascular response of the chorioallantoic membrane to TAF preparations. All of the viral transformed and tumor-derived cells tested, including SVT2, SVW126, Welker 256 rat carcinoma, B-16 mouse melanoma, human glioblastoma, and human meningioma cells, produced TAF. The potency of the TAF preparations, as measured by the number of cells needed to induce a positive vascular response on the chorioallantoic membrane, varied from cell line to cell line. The most potent cells tested were the glioblastoma and maningioma brain tumor cells. Since these brain tumors are found to be the most highly vascularized tumors in vivo, it was concluded that a correlation exists between the vascularity of a tumor in vivo and the potency of TAF in vitro. There was no detectable angiogenesis activity induced by density-inhibited BALB/c primary mouse embryo or early-passage human skin fibroblasts, even when relatively large numbers of cells were used to make a sample. However, density-inhibited BALB/c 3T3 aan W138 human embryonic lung fibroblasts, two cell lines widely regarded as demonstrating "normal" growth behavior in culture, produced TAF. From these and other observations, it was suggested that BALB/c 3T3 and W138 are not fully "normal" cells. Furthermore, it was suggested that the production of TAF is an early event in the cell transformation process that precedes the loss of density inhibition of growth in vitro.

Angiogenesis Inducing Agents↗
PubMed1976

Prolonged tumor dormancy by prevention of neovascularization in the vitreous.

Tumors release a diffusible substance that stimulates neovascularization. To study the neovascularization that occurs in diabetic retinopathy, we implanted V2 carcinomas and mouse ependymoblastomas into the vitreous of experimental animals. In the vitreous, unlike previous sites, the tumors failed to stimulate neovascularization. They grew for weeks as small, unvascularized, three-dimensional aggregates of cells. Explosive growth into a large, vascularized mass occurred when the avascular tumors reached the retinal surface. The vitreous proved to be a valuable model for observing the in vivo growth of small, solid tumors. Xenografts survived for months without evidence of immune rejection. The consequence of the prolonged avascular state is the restriction of tumor size. The normal vitreous may act to inhibit capillary proliferation. An understanding of the mechanism for maintaining the avascular state may lead to therapeutic blockade of neovascularization. This would be important in the management of diabetic retinopathy and neoplasia.

Animals↗
PubMed1975

Influence of geometry on control of cell growth.

The assembled evidence suggests that geometry plays an important role in regulation of cell growth, at least at two levels: (1) For non-transformed individual cells in culture, there may be a continuous range of shapes, from spherical all the way to extremely flat or extended, which correlates with increasing proliferative capacity or increasing ability to respond to serum growth factors. In other words, sensitivity to a variety of mitotic stimulators and growth factors may be modulated by cell conformation. Fully transformed cells appear to lose the modulating effect of shape, and thus are able to proliferate even when spherical. (2) For transformed cells which can grow in three-dimensional populations, the shape of the population itself eventually limits growth. The most likely mechanism is based upon the limiting effects of diffusion gradients of nutrients, oxygen and catabolites which build up across the surface of a three-dimensional population of cells. Tumor cells which are able to make tumour angiogenesis factor (TAF), induce new capillary blood vessels from the host. These vessels penetrate the tumor and permit further rapid growth. In this sense, tumor angiogenesis is a mechanism by which "successful" tumors escape the growth restriction imposed upon three-dimensional cell population by geometry [49].

Animals↗
PubMed1975

Tumor-induced angiogenesis: lack of inhibition by irradiation.

The effect of irradiation of tumors on their ability to induce vascular responses (angiogenesis) was studied. Rat Walker carcino-sarcoma 256, rabbit V2 carcinoma, mouse (C57B1) melanoma and mouse (129) teratoma (OTT 6050, 100K) were irradiated with up to 5000R, then grafted either to the chicken chorioallantoic membrane or intracorneally into adult rabbits to assess competence to provoke angiogenesis. For all tumors and both assay systems the results were similar: irradiation did not interfere with tumor-induced vascular responses.

Angiogenesis Inducing Agents↗
PubMed1975

Inhibition of tumor angiogenesis mediated by cartilage.

Capillary proliferation induced by tumor is shown to be inhibited by neonatal scapular cartilage. Using the rabbit cornea as an assay, the cartilage implant decreased the rate of capillary growth, induced by tumor, by an average of 75%. Vascularization was prevented completely in 28% of tumors. The inhibitory effect of small cartilage implants operates over distances of up to 2.0 mm and displays a gradient from the cartilage source. The experiments suggest that the cartilage inhibitor does not antagonize tumor angiogenesis factor, but appears to inhibit capillary proliferation directly. The inhibitory material does not elicit an inflammatory response in either the rabbit cornea or in the chick chorioallantoic membrane. Thus with further purification, it may prove useful as a means of maintining tumor dormancy by "antiangiogenesis."

Animals↗
PubMed1975

Oxygen consumption by acrylamide polymerization: a method for rapid screening of anticancer agents.

We have developed a rapid and sensitive method to measure oxygen consumption of tumor cells by acrylamide polymerization. This method could be used as an in vitro screen for potential chemotherapeutic agents. Previous techniques have lacked either the sensitivity or the speed required for use as an effective clinical tool. This method was modified from a technique previously developed in our laboratory for measuring oxygen in blood. Standard anticancer agents were tested against Walker 256 ascites tumor. Ascites was harvested from 20 rats on each of 50 days, incubated briefly with drugs, and acrylamide polymerization time was measured hourly. Individual controls were established for each drug-treated group, and oxygen uptake measured after one hour of incubation. Actinomycin, cyclohexamide, and cytosine arabinoside inhibited tumor cell oxygen consumption by 80%, 40%, and 30%, respectively. These results correlated with the known in vivo effects of these drugs on Walker carcinosarcoma. Therefore, this sensitive method could potentially be used directly on tumor cells removed from biopsy material so that the testing of anticancer drugs could be completed on the day of biopsy.

Acrylamides↗
PubMed1975

Vascularization of normal and neoplastic tissues grafted to the chick chorioallantois. Role of host and preexisting graft blood vessels.

Adult, embryonic, and tumor tissues were grafted to the chorioallantoic membrane of the chick embryo to determine whether blood vessels originally within implants were reused in the establishment of a new blood supply. Grafts were examined daily by in vivo stereomicroscopy and in histologic sections. Colloidal carbon injections into the host vasculature served to confirm the precise onset of graft circulation; Preexisting tumor blood vessels disintegrated by 24 hours after implantation and revascularization occurred at 3 days by penetration of proliferating host vessels into the tumor tissue. Adult tissues did not revascularize, and the original graft vasculature progressively disintegrated during the 9 days of observation, Most embryonic tissues revascularized in 1 or 2 days by reperfusion of the existing graft vasculature. Anastomosis of host and graft blood vessels seemed to result from connections between newly formed vascular sprouts arising from both vasculatures. This study indicates that only tumor grafts acquire their blood supply solely by formation of new blood vessels from the host microvasculature. By contrast revascularization of normal tissues, when it does occur, is predominately the result of perfusion of the preexisting graft blood vessels.

Allantois↗
PubMed1975

Pyloromyotomy: Does surgery in infancy increase allergy?

One recently published article and several presentations at international meetings have suggested that there is an increased incidence of allergic and asthmatic manifestations, as compared with the general population, if a child undergoes surgery before the age of 2 years. The study explores the incidence of asthma and allergy in a group of patients who presented with pyloric stenosis. All of these underwent surgery. The technique of the study was a retrospective telephone review and the response rate was approximately 40%. The data show that there is no increase in the incidence of allergy or asthma in this population as compared with nationally reported figures.

Adolescent↗