Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1519670 (tumor angiogenesis)
 6,052 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous reports on the slower growth of tumors in senescent mice have suggested a decrease in tumor angiogenesis in these animals, but such an observation has not yet been documented quantitatively. In this study, we report the relative amount of tumor angiogenesis and tumor volume for two different types of tumor in 11 young (8-9-wk old) versus nine older (19-mo old) male C57BL/10 mice. B16 melanoma or SP1 methylcholanthrene-induced fibrosarcoma cells were injected into the ventral skin of mice. After 3 days, the mice were killed and the injection sites were examined for angiogenesis surrounding the tumor (centrally directed tumor angiogenesis), nerve-associated angiogenesis, and tumor volume. In the older mice, there was significantly less centrally directed tumor angiogenesis for both tumors tested, and nerve-associated angiogenesis was decreased for B16 melanoma. The mean tumor volume for the B16 implants was smaller for the older animals, but the mean SP1 tumor volumes were identical for both age groups. These findings support the hypothesis that tumor growth in older animals is associated with less formation of new blood vessels, and this may explain the slower tumor growth observed in aged animals with certain experimental tumors.
 ...
PMID:Effect of host age on tumor-associated angiogenesis in mice. 168 82

Microvascular proliferation, a hallmark of malignant brain tumors, represents an attractive target of anticancer research, especially because of the quiescent nonproliferative endothelium of the normal brain. Cerebral neoplasms sequester copper, a trace metal that modulates angiogenesis. Using a rabbit brain tumor model, normocupremic animals developed large vascularized VX2 carcinomas. By contrast, small, circumscribed, relatively avascular tumors were found in the brains of rabbits copper-depleted by diet and penicillamine treatment (CDPT). The CDPT rabbits showed a significant decrease in serum copper, copper staining of tumor cell nuclei, microvascular density, the tumor volume, endothelial cell turnover, and an increase in the vascular permeability (breakdown of the blood-brain barrier), as well as peritumoral brain edema. In non-tumor-bearing animals, CDPT did not alter the vascular permeability or the brain water content. CDPT also inhibited the intracerebral growth of the 9L gliosarcoma in F-344 rats, with a similar increase of the peritumoral vascular permeability and the brain water content. CDPT failed to inhibit tumor growth and the vascularization of the VX2 carcinoma in the thigh muscle or the metastases to the lung, findings that may reflect regional differences in the responsiveness of the endothelium, the distribution of copper, or the activity of cuproenzymes. Metabolic and pharmacologic withdrawal of copper suppresses intracerebral tumor angiogenesis; angiosuppression is a novel biologic response modifier for the in situ control of tumor growth in the brain.
 ...
PMID:Inhibition of angiogenesis and tumor growth in the brain. Suppression of endothelial cell turnover by penicillamine and the depletion of copper, an angiogenic cofactor. 170 Jun 17

Malignant gliomas are difficult to treat systemically because of exclusion of many chemotherapeutic agents by the blood brain barrier. Furthermore, as opposed to other neoplasms, malignant gliomas recur locally, at the site of original presentation. These tumors are remarkably vascular and hence may be more dependent on angiogenesis for continued growth than other tumors. The inhibition of tumor angiogenesis can control tumor growth by preventing the exponential vascular growth phase. We report the inhibition of the growth of the 9L glioma by the localized, controlled release of known angiogenesis inhibitors administered in a biodegradable polyanhydride polymer matrix. In the presence of heparin and cortisone and of cortisone alone there was a 4.5- and 2.3-fold reduction, respectively, in the growth of the 9L glioma. We compared these results to the inhibition of tumor neovascularization in the rabbit cornea by the localized delivery of the same agents. In the rabbit cornea model, the local release of heparin and cortisone and of cortisone alone resulted in a 2.5- and 2.0-fold reduction, respectively, in the angiogenesis response evoked by the VX2 carcinoma. This study introduces two new potential therapeutic modalities for the treatment of malignant gliomas: the use of the combination of heparin and cortisone as antineoplastic agents and the use of polymeric carriers for the local delivery of such agents in the central nervous system.
 ...
PMID:Growth inhibition of the 9L glioma using polymers to release heparin and cortisone acetate. 170 49

A method is reported for the study of early phases of neovascularization in syngeneic murine tumors and human tumor xenografts in nude mice. Using this method, the effect of irradiation of tumor cells or tumor bed on tumor angiogenesis was studied. Tumor cells were injected intradermally in the abdominal skin flap, which was reopened at 2-day intervals to quantify newly formed blood vessels at the site of tumor cell injection. Both tumor cell injection and blood vessel counting were performed under a dissecting microscope. Using three syngeneic murine tumors and two clones of a human colonic adenocarcinoma, it was observed that new blood vessels started appearing within a few days after tumor cell injection and that this event preceded measurable tumor growth. The number of blood vessels increased exponentially for several days but then their further growth slowed. The extent of angiogenesis depended on the tumor type and the number of tumor cells injected. The exposure of the skin flap to ionizing radiation prior to tumor cell injection reduced neovascularization. We further observed that heavily irradiated tumor cells retained their ability to induce angiogenic response and that lymphoid cells (peritoneal exudate and spleen cells) could also elicit an angiogenic response, although it is weaker than the response elicited by tumor cells. Thus this method is suitable for quantification and kinetics of early phases of tumor angiogenesis in individual mice bearing transplants of syngeneic tumors or human tumor xenografts, and it can be useful for investigating various regulators of tumor angiogenesis.
 ...
PMID:An intradermal assay for quantification and kinetics studies of tumor angiogenesis in mice. 170 92

Vascular permeability factor (VPF) is a highly conserved 34-42-kD protein secreted by many tumor cells. Among the most potent vascular permeability-enhancing factors known, VPF is also a selective vascular endothelial cell mitogen, and therefore has been called vascular endothelial cell growth factor (VEGF). Our goal was to define the cellular sites of VPF (VEGF) synthesis and accumulation in tumors in vivo. Immunohistochemical studies were performed on solid and ascites guinea pig line 1 and line 10 bile duct carcinomas using antibodies directed against peptides synthesized to represent the NH2-terminal and internal sequences of VPF. These antibodies stained tumor cells and, uniformly and most intensely, the endothelium of immediately adjacent blood vessels, both preexisting and those newly induced by tumor angiogenesis. A similar pattern of VPF staining was observed in autochthonous human lymphoma. In situ hybridization demonstrated VPF mRNA in nearly all line 10 tumor cells but not in tumor blood vessels, indicating that immunohistochemical labeling of tumor vessels with antibodies to VPF peptides reflects uptake of VPF, not endogenous synthesis. VPF protein staining was evident in adjacent preexisting venules and small veins as early as 5 h after tumor transplant and plateaued at maximally intense levels in newly induced tumor vessels by approximately 5 d. VPF-stained vessels were also hyperpermeable to macromolecules as judged by their capacity to accumulate circulating colloidal carbon. In contrast, vessels more than approximately 0.5 mm distant from tumors were not hyperpermeable and did not exhibit immunohistochemical staining for VPF. Vessel staining disappeared within 24-48 h of tumor rejection. These studies indicate that VPF is synthesized by tumor cells in vivo and accumulates in nearby blood vessels, its target of action. Because leaky tumor vessels initiate a cascade of events, which include plasma extravasation and which lead ultimately to angiogenesis and tumor stroma formation, VPF may have a pivotal role in promoting tumor growth. Also, VPF immunostaining provides a new marker for tumor blood vessels that may be exploitable for tumor imaging or therapy.
 ...
PMID:Distribution of vascular permeability factor (vascular endothelial growth factor) in tumors: concentration in tumor blood vessels. 194 Aug 5

We analysed the growth pattern of metastases in C3H-mice produced by i.v. injection (tail vein) of tumor cell suspensions of mammary carcinoma HB. Although the ordinary Gompertz equation generally corresponds well to tumor growth in animals and men, we found it inadequate to describe the growth of lung metastases in our model. The morphometric analysis and growth kinetics (LI/GF) of the metastases show a biphasic pattern. The first phase is characterized by a strictly avascular growth and nutrition by diffusion, the second phase is initiated by tumor angiogenesis. To analyze these observations we developed a new mathematical equation which fits particularly well to the metastatic growth curve. We conclude that the present model is appropriate for the analysis of tumor angiogenesis, especially to study factors, which influence the development of a tumor specific vascular system.
 ...
PMID:A mathematical model for metastatic growth illustrated by in vivo and in vitro growth of a transplantable mammary carcinoma in mice. 242 82

The growth of five different kinds of human choriocarcinoma cell lines in vitro was quite alike. However, two distinct types of rapid and slow growth were observed in tumors grown in the hamster cheek pouch. The rapidly grown tumor tissues (BeWo, JEG-3, and NUC-1) involved significantly large numbers of blood vessels per microscopic field, as compared to slowly grown ones (SCH and HM). The vascular response was assayed using cell-free crude tumor angiogenesis factors (TAF) on chorioallantoic membrane (CAM) of the chick embryo. In all cell lines TAF activity correlated well with the extent of tumor growth in vivo. Gel filtration analysis showed that relatively high-molecular-weight (more than 10,000) factors could induce neovascularization in the both assays using CAM and rabbit cornea. These results suggest that a heterogeneity of TAF activity is present among human choriocarcinoma cell lines and tumor growth in xenograft depends on the secretion of TAF by the tumor cells themselves.
 ...
PMID:Tumor angiogenesis activity of human choriocarcinoma cells grown in vitro. 243 Aug 62

The effect of "antiangiogenesis" therapy using cortisone acetate (CA) with or without heparin on tumor growth as well as in combination with chemotherapy was investigated. C3H mice were implanted intradermally with N-[4-(5-nitro-2-furyl)-thiazolyl]formamide induced undifferentiated transitional cell carcinoma, MBT-2, in the right flank. The treatment was initiated 9 to 10 days after tumor inoculation. Daily injections of CA (250 mg/kg s.c.) suppressed tumor growth significantly in a dose dependent fashion. Administration of heparin (Elkins-Sinn) at the concentration of 200, 400, or 1000 units/ml in drinking water for 3 to 6 days was neither additive nor detrimental to the effect of CA. Chemotherapy was combined with CA; 3 days of administration of 250 mg/kg of CA in tapering doses was used. The chemotherapeutic agent was injected once 24 h before the initial CA. Combinations of chemotherapy (Adriamycin, 2.5-7.5 mg/kg i.v; cisplatin, 3-9 mg/kg i.p.; cyclophosphamide, 50-150 mg/kg i.p.; cis-(diammino)(1,1-cyclobutanedicarboxylate)platinum(II) (JM-8), 60-150 mg/kg i.p.; mitomycin C, 3-4.5 mg/kg i.p.) with CA showed additive suppression of tumor growth. Mice tolerated chemotherapy alone, CA alone, and both in combination. CA combined with JM-8 was not tolerated. Mice tolerated 100 to 150 mg/kg of JM-8, whereas the addition of CA to JM-8 resulted in a 66% (6 of 9) to 89% (8 of 9) mortality rate. CA at a concentration of 5 and 25 micrograms/ml showed no direct cytotoxic activity against MBT-2 cells in vitro. However, 3 days of administration of 250 mg/kg of CA inhibited tumor angiogenesis generated by MBT-2 cells in C3H mice using a dorsal air sac assay. The data suggest that CA alone inhibits tumor angiogenesis in C3H mice and that antiangiogenesis therapy enhances the antitumor efficacy of chemotherapeutic agents without increasing host toxicity (except for JM-8).
 ...
PMID:Efficacy of antitumor chemotherapy in C3H mice enhanced by the antiangiogenesis steroid, cortisone acetate. 244 60

Tumor angiogenic activity (TAA) from tumor angiogenesis factor (TAF), produced by 24 cell lines of various kinds of gynecologic tumors, was assayed onto chorioallantoic membranes (CAMs) of chick embryos. Methylcellulose (1%) pellets containing 1 x 10(7) cells were placed on 8-day-old postfertilized CAMs, and the grade of neovascularization was assayed 3 days after inoculation. Neovascularization occurred prominently in such cell lines, as HTBOA (poorly differentiated ovarian carcinoma), HUOCA-II (poorly differentiated clear cell adenocarcinoma), HWUA (poorly differentiated endometrial adenocarcinoma), and in HKUS (uterine cervical small cell carcinoma); however, neovascularization did not occur in SNK (uterine leiomyosarcoma line). The cell lines which secreted TAF showed high heterotransplantability in the nude mice and produced rapidly growing tumors which were rich in blood vessels. However, the SKN line which did not secret TAF was not transplantable. These results suggested that there was a close relationship among TAA, transplantability, and tumor growth rate.
 ...
PMID:Tumor angiogenic activity of gynecologic tumor cell lines on the chorioallantoic membrane. 244 91

A model for the study of tumor angiogenesis within the rabbit brain is presented. Implantation of the VX2 carcinoma provides a reproducible tumor accompanied by angiogenesis. The authors report the sequential growth, histology, tumor neovascularization, and vascular permeability of this tumor following its intracerebral implantation. Tumor angiogenesis correlates with the rapid and logarithmic intracerebral tumor growth. The proliferation of blood vessels in the tumor and the organization of tumor cells around tumor vessels are described. Breakdown of the blood-brain barrier (detected by Evans blue leakage) starts in the early stages of tumor development and becomes prominent as the tumor vasculature and size increase. This model is useful for experimental studies of angiogenesis.
 ...
PMID:Neovascularization and tumor growth in the rabbit brain. A model for experimental studies of angiogenesis and the blood-brain barrier. 245 89


1 2 3 4 5 6 7 8 9 10 Next >>