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Biomedical subjects

J Folkman

Publications and source records attributed to J Folkman.

At least 217 records · Page 12Linked to original sources
PubMed1985

Angiogenesis is stimulated by a tumor-derived endothelial cell growth factor.

A growth factor mitogenic for BALB/C 3T3 cells and capillary endothelial cells was isolated from a rat chondrosarcoma and purified to homogeneity. Purification was accomplished by a combination of BioRex 70 cation exchange chromatography and heparin affinity chromatography. The pure chondrosarcoma-derived growth factor (ChDGF) had a molecular weight of about 18,000. The angiogenesis activity of pure ChDGF was tested by measuring its ability to vascularize the chorioallantoic membrane (CAM) and yolk sac membrane of the developing chick. The ability of ChDGF to induce the growth of limbal vessels in the rat cornea was also measured. To quantitate the angiogenesis response, a unit system based on the growth factor activity of ChDGF for 3T3 cells was adopted. ChDGF was found to have a specific activity of about 5 units/ng when applied to 3T3 cells. About 300-600 units of ChDGF in the two types of developing chick membrane and 30-5 units of ChDGF in the rat cornea were found to stimulate noninflammatory angiogenesis.

Animals↗
PubMed1985

Tumor angiogenesis.

The hypothesis that tumors are angiogenesis dependent has, in the past decade, generated new investigations designed to elucidate the mechanism of angiogenesis itself. Many laboratories are now engaged in this pursuit. Some are studying angiogenesis that occurs in physiological situations, whereas others are interested in angiogenesis that dominates pathological conditions. These efforts have led to (1) the development of bioassays for angiogenesis; (2) the partial purification and, in one case, the complete purification of angiogenic factors from neoplastic and non-neoplastic cells; (3) the development of new polymer technology for the sustained release of these factors and other macromolecules in vivo; (4) the cloning and long-term culture of capillary endothelial cells; (5) the demonstration of the role of nonendothelial cells, such as mast cells in modulating angiogenesis; (6) the discovery of angiogenesis inhibitors; and (7) the demonstration that certain animal tumors will regress when angiogenesis is inhibited. The effects of angiogenesis inhibitors provide perhaps the most compelling evidence for the role of angiogenesis in tumor growth. It is conceivable that the original effort to understand the role of angiogenesis in tumor growth will also lead to the use of angiogenesis inhibitors as a new class of pharmacologic agents in a variety of non-neoplastic diseases such as arthritis, psoriasis, and ocular neovascularization. However, much work remains to be done before it will be possible to understand (1) the regulatory systems that govern capillary density in normal tissues; (2) the factors that maintain the viability of microvascular endothelium; (3) the development of the vascular system itself; and (4) the mechanism by which vascular regression occurs, both in the embryo and in the postnatal organism. A knowledge of the mechanisms which underlie these normal processes may help to enlarge our comprehension of tumor angiogenesis.

Angiogenesis Inducing Agents↗
PubMed1985

Angiogenesis and its inhibitors.

The hypothesis that solid tumors are angiogenesis-dependent has, in the past decade, generated much new work aimed at understanding the mechanism of angiogenesis itself. Many laboratories in this country and abroad are now studying some aspect of this intriguing problem. Some investigations are focused mainly on tumor angiogenesis, whereas others are centered on angiogenesis that occurs in physiologic situations or that dominates certain non-neoplastic pathologic states. These efforts have brought about [a] the development of bioassays for angiogenesis; [b] the partial purification (and in one case the complete purification) of angiogenic factors from neoplastic and non-neoplastic cells; [c] the development of new polymer technology for the sustained release of these factors and of other macromolecules in vivo; [d] the cloning and long-term culture of capillary endothelial cells; [e] the demonstration of the role of nonendothelial cells, such as mast cells, in modulating angiogenesis; [f] the discovery of angiogenesis inhibitors; and [g] the recent demonstration that certain animal tumors will undergo complete regression when treated by antiangiogenesis alone. The effects of angiogenesis inhibitors provide the most compelling evidence for the role of angiogenesis in tumor growth. That it is now possible not only to inhibit tumor growth but also to eradicate some experimental tumors speaks strongly for a therapeutic approach that may some day be useful in clinical oncology. Conceivably, the original goal to understand the role of angiogenesis in tumor growth will lead to the use of angiogenesis inhibitors in other non-neoplastic diseases.

Animals↗
PubMed1984

Heparin affinity: purification of a tumor-derived capillary endothelial cell growth factor.

A tumor-derived growth factor that stimulates the proliferation of capillary endothelial cells has a very strong affinity for heparin. This heparin affinity makes it possible to purify the growth factor to a single-band preparation in a rapid two-step procedure. The purified growth factor is a cationic polypeptide, has a molecular weight of about 18,000, and stimulates capillary endothelial cell proliferation at a concentration of about 1 nanogram per milliliter.

Angiogenesis Inducing Agents↗
PubMed1984

Protamine: a powerful in vivo inhibitor of bone resorption.

Protamine is shown to be a powerful disrupter of calcium homeostasis, acutely inducing a severe hypocalcemia in both rabbits and rats. The magnitude of its effect correlates with bone turnover. Protamine does not significantly alter the renal excretion of calcium, and is effective whether or not there is calcium present in the gut. Protamine causes a significant fall in the specific activity of 45Ca in the blood in animals whose bone has been prelabeled with 45Ca. These data suggest that protamine induces hypocalcemia by blocking calcium efflux from bone. Further work seems indicated to define the biochemical mechanism of this action.

Animals↗
PubMed1984

Prevention of carcinomatosis and bloody malignant ascites in the rat by an inhibitor of angiogenesis.

It has previously been shown that protamine sulfate is an angiogenesis inhibitor. Regional infusion of protamine into the peritoneal cavity is now reported to prevent the growth of intraperitoneal vascularized tumor masses in rats. Walker 256 carcinoma was implanted directly into the liver or into the peritoneal cavity of rats. Hepatic implants grew in the liver with metastases to the wound and mesentery. Injected tumor cells grew as solid tumor masses in the mesentery. Bloody ascites developed after 7 days. Animals received an intraperitoneal infusion of protamine or saline. Protamine significantly inhibited growth of solid tumors in the mesentery (P less than 0.001). Histology showed tumor cells growing only in monolayer but without vascularization. Ascites was not bloody. In saline-treated animals large vascularized tumors grew in the peritoneal cavity and ascites became bloody.

Animals↗
PubMed1984

Toward a new understanding of vascular proliferative disease in children.

These studies provide the following evidence: (1) Angiogenesis is a multistep process. (2) The steps necessary to construct a capillary must occur in correct sequence, a motif that seems to be expressed entirely by vascular endothelial cells. (3) Primary tumors and their metastases are angiogenesis dependent, and angiogenesis may be a critical control point in tumor growth. (4) Heparin potentiates angiogenesis. (5) Heparin or its nonanticoagulant fragments, administered with cortisone, inhibit angiogenesis. (6) Heparin is degraded in the gastrointestinal tract and yields low molecular weight fragments, some of which are absorbed into the circulation. (7) There is a group of corticosteroids that inhibit angiogenesis in the presence of a heparin fragment, but have no glucocorticoid or mineralocorticoid activity. The compounds to which this new biologic activity has been assigned have been named "angiotropic" steroids. (8) There is a potential future role for angiogenesis inhibitors as a new class of pharmacologic agents.

Angiogenesis Inducing Agents↗
PubMed1983

Angiogenesis inhibition and tumor regression caused by heparin or a heparin fragment in the presence of cortisone.

Heparin or a heparin fragment administered with cortisone inhibited angiogenesis, caused regression of large tumor masses, and prevented metastases. Oral administration of heparin resulted in the release of non-anticoagulant heparin fragments in the serum which, in the presence of cortisone, had similar anti-angiogenic and antitumor effects. Of all the heparin fragments tested, the most potent inhibition of angiogenesis in the presence of cortisone was provided by a hexasaccharide with a molecular weight of about 1600.

Animals↗
PubMed1983

The role of heparin in angiogenesis.

A series of experiments is described in which: (i) mast cells were found to accumulate at a tumour site before the ingrowth of new capillaries; (ii) heparin released by mast cells increased the migration of capillary endothelial cells in vitro; and (iii) heparin enhanced tumour angiogenesis in vivo. These experiments led to the discovery that protamine and platelet factor 4 are angiogenesis inhibitors. This finding suggests a central role for heparin or related glycosaminoglycans in the growth regulation of capillary blood vessels.

Angiogenesis Inducing Agents↗
PubMed1983

Cell shape and phenotypic expression in chondrocytes.

The relationship between cell shape, proliferation, and phenotypic expression was studied in human chondrocytes. Shape was controlled independent of serum concentration, anchorage, and cell density by alteration of substratum adhesiveness with poly(2-hydroxyethyl methacrylate) (poly[HEMA]). Cells that were held rounded displayed features of the chondrocyte phenotype; i.e., they were round, proliferated slowly, incorporated low levels of [3H]thymidine into DNA, and incorporated large amounts of 35SO4 into glycosaminoglycans. In contrast, cells that were held flat were fibroblast-like: they exhibited flattened morphology, more rapid growth, greater incorporation of [3H]thymidine, and less incorporation of 35SO4. These studies suggest that cell shape may play an important role in phenotypic expression in chondrocytes.

Cartilage↗