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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibroblast growth factors (FGFs) are widely recognized as a family of molecules that can influence cell proliferation and tissue neovascularization. Although the basic form of FGF (bFGF) has been found to enhance the growth of primary cell cultures made from human glial tumors, its exact role in vivo has been unclear. Likewise, vascular endothelial growth factor (VEGF) is a newly discovered addition to the growing list of angiogenic factors but, unlike bFGF, VEGF has a unique specificity for endothelial cells and possesses the properties required for secretion. In this study, we localized both basic FGF and VEGF in human gliomas to assess their possible role in the pathogenesis of these neoplasms. Retrospective analysis was performed using glial neoplasms that were fixed in 10% neutral buffered formalin and embedded in paraffin. The immunocytochemical procedures were performed using specific polyclonal antibodies raised against the amino terminus of bFGF and VEGF, respectively. Immunoreactive (IR) basic FGF was localized in normal, reactive, and neoplastic astrocytes as well as selected populations of normal neurons. IR VEGF, in contrast, was present primarily in neurons of normal brain, but was also found in both reactive and neoplastic astrocytes. In adjacent 4-microns tissue sections, strong immunoreactivity for VEGF and bFGF was found within the same populations of cells. In areas of endothelial proliferation, the strongest immunoreactivity for both growth factors was found within large anaplastic astrocytes that surrounded abnormal blood vessels. Our data support the hypothesis that VEGF may complement the actions of basic FGF in glial neoplasia.
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PMID:Localization of basic fibroblast growth factor and vascular endothelial growth factor in human glial neoplasms. 149 34

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), increases microvascular permeability and is a specific mitogen for endothelial cells. Expression of VPF/VEGF previously was demonstrated in a variety of tumor cells, in cultures of pituitary-derived cells, and in corpus luteum. Here we present evidence, by Northern analysis and in situ hybridization, that the VPF/VEGF gene is expressed in many adult organs, including lung, kidney, adrenal gland, heart, liver, and stomach mucosa, as well as in elicited peritoneal macrophages. The highest levels of VPF/VEGF transcripts were found in epithelial cells of lung alveoli, renal glomeruli and adrenal cortex, and in cardiac myocytes. The prominence of VPF/VEGF mRNA in these tissues suggests a possible role for VPF/VEGF in regulating baseline microvascular permeability, which is essential for tissue nutrition and waste removal. We also demonstrate particularly high VPF/VEGF mRNA levels in several human tumors, where it may be involved in promoting tumor angiogenesis and stroma generation, both as an endothelial cell mitogen and indirectly by its permeability enhancing effect that leads to the deposition of a provisional fibrin gel matrix.
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PMID:Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors. 155 Sep 62

PCR cloning and cDNA sequencing have been used to identify mRNAs of two splice products of the vascular endothelial growth factor (VEGF) gene, VEGF121 and VEGF165, in cells isolated from Kaposi's sarcomas (KS) of AIDS patients (AIDS-KS). As demonstrated by Northern blot analysis, AIDS-KS cells as well as tumor cells show a high expression level of the VEGF gene as compared to primary human vascular cells like smooth muscle cells or endothelial cells. In addition to the lower expression of the gene, vascular cells express a 3.9 kb band together with a 3.2 kb band instead of a 3.9 kb and a 4.3 kb band in AIDS-KS cells. Our data suggest that the angiogenic properties of AIDS-KS cells might be mediated by the secretion of this growth factor and that this factor alone or in combination with other endothelial mitogens may be involved in endothelial proliferation associated with Kaposi's sarcoma.
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PMID:AIDS-associated Kaposi's sarcoma cells in culture express vascular endothelial growth factor. 156 95

Future advances in neuro-oncology will increasingly rely on an understanding of the molecular biology of brain tumors. Recent laboratory work, including the identification of oncogenes and tumor suppressor genes, has elucidated many of the molecular events contributing to oncogenesis. In particular, the signaling pathways for the growth factors have been implicated in the genesis and the maintenance of several human tumors, including neoplasms of the central nervous system (CNS). Growth factor autocrine and paracrine stimulatory loops promote tumor proliferation and angiogenesis. A family of structurally related growth factor receptors, the receptor tyrosine kinases, are particularly relevant to tumors of the CNS. This large family includes the receptors for the epidermal growth factor, the platelet-derived growth factor, the fibroblast growth factor, the insulin-like growth factor, the neurotrophins related to the nerve growth factor, and the vascular endothelial growth factor, as well as several receptors for which no growth factor ligand has been identified. Several of these receptor molecules and their growth factor ligands are preferentially expressed in the embryonic brain and are thought to play a central role in regulating the determination of the cell fate during the development of the CNS. Moreover, the overexpression or the mutation of genes encoding these receptors can be oncogenic. Researchers think that some receptors in this family (i.e., those that have been shown to be overexpressed or mutated in human brain tumors) contribute to brain tumor oncogenesis. This article will focus on recent experimental work and will discuss the classification and the biology of the receptor tyrosine kinases, as well as their roles in the development of the CNS and in tumorigenesis.
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PMID:The role of growth factor receptors in central nervous system development and neoplasia. 747 68

A series of 130 eyes with ocular melanomas, 19 normal eyes, and 18 eyes affected with other disorders leading to blood-ocular barrier (BOB) breakdown were immunohistochemically stained for albumin to localize sites of BOB failure within the retina, ciliary body, and iris. Thirty-nine of the eyes containing melanomas and all of the other eyes were also immunohistochemically stained for vascular endothelial growth factor (VEGF), to investigate its potential role as a mediator for BOB failure. Eyes with melanomas showed widespread leakage through the retinal pigment epithelium, and 58% demonstrated leakage from retinal vessels in the proximity of the tumor. BOB failure remote from the tumor also occurred in retina (50%), optic nerve head (77%), ciliary body (51%), and iris (51%), suggesting that a soluble mediator may be involved. VEGF was demonstrated intraretinally in the proximity of (46%) and remote from (24%) melanomas and in eyes affected by other disease processes, particularly those involving neoplasia or retinal detachments, usually within particular cell populations (ie, retinal vessel walls, ganglion cells, inner or outer nuclear layers, retinal pigment epithelium). VEGF localization in retina, ciliary body, and iris often coincided with sites of extravasated albumin. Preincubation of albumin or VEGF antibodies with normal serum or VEGF peptide, respectively, eliminated or markedly reduced all immunoreactivity. Only 1 of 14 normal postmortem eyes and 0 of 5 normal surgically removed eyes showed VEGF positivity in the retina, 5 of 19 normal eyes had weak positivity in the ciliary body, and VEGF was not demonstrated in the iris of normal eyes. VEGF cannot account for all of the BOB failure associated with ocular melanomas, but appears likely to play a contributing role in many cases.
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PMID:Blood-ocular barrier breakdown in eyes with ocular melanoma. A potential role for vascular endothelial growth factor/vascular permeability factor. 748 92

Cerebral edema and fluid-filled cysts are common accompaniments of brain tumors. They contribute to the mass effect imposed by the primary tumor and are often responsible for a patient's signs and symptoms. Cerebral edema significantly increases the morbidity associated with tumor biopsy, excision, radiation therapy, and chemotherapy. Both edema and cyst formation are thought to result from a deficiency in the blood-brain barrier, with consequent extravasation of water, electrolytes, and plasma proteins from altered tumor microvessels. The resultant expansion of the cerebral interstitial space contributes to the elevated intracranial pressure observed with brain tumors. Departure from the typical blood-brain barrier microvascular architecture may only partially explain the occurrence of edema and tumor cyst formation. Biochemical mediators have also been implicated in vascular extravasation. Vascular permeability factor or vascular endothelial growth factor (VPF/VEGF) is a protein that has recently been isolated from a variety of tumors including human brain tumors. VPFb is an extraordinarily potent inducer of both microvascular extravasation (edemagenesis) and the formation of new blood vessels (angiogenesis). Its role in tumor growth and progression would therefore appear pivotal. Herein, the author presents an updated account of the investigation of VPF. Historical and clinical perspectives of the study and treatment of tumor associated edema are provided. The efficacy of high-dose dexamethasone in the treatment of neoplastic brain edema is discussed. A hypothetical role for VPF in edemagenesis is presented and discussed. It is hoped that an expanded understanding of the mechanisms responsible for the genesis of edema will ultimately facilitate therapeutic intervention.
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PMID:The genesis of peritumoral vasogenic brain edema and tumor cysts: a hypothetical role for tumor-derived vascular permeability factor. 751 4

The presence of mRNAs for vascular endothelial growth factor (VEGF) and a VEGF-related protein, placenta growth factor (PIGF) was examined in 29 cases of renal cell carcinoma tissues and adjacent normal kidney tissues and in 4 human renal cell carcinoma cell lines. Northern blot analysis showed that 26 of 27 hypervascular renal cell carcinoma tissues (96%) exhibited a markedly elevated level (3-13 fold) of VEGF mRNA compared to the adjacent normal kidney tissues. Even tumors of small size, whenever they were hypervascular, overexpressed VEGF mRNA. We also demonstrated that mRNA for PIGF was expressed in 21 of 23 hypervascular renal cell carcinoma tissues (91%) but was not detected in the adjacent normal kidney tissues. Two hypovascular carcinoma tissues neither overexpressed VEGF mRNA nor had PIGF mRNA. VEGF mRNA was detected in four human renal cell carcinoma cell lines, while PIGF mRNA was not. There was no difference in the level of basic fibroblast growth factor mRNA between tumor tissues and normal kidney tissue, although our previous study demonstrated elevated basic fibroblast growth factor protein in the serum of renal cell carcinoma patients (K. Fujimoto et al., Biochem. Biophys. Res. Commun., 180: 386-392, 1991). Taken together, these results suggest that VEGF, PIGF, and basic fibroblast growth factor are cooperatively working to increase the angiogenesis in renal cell carcinoma in vivo.
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PMID:Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis. 751 52

Meth-A sarcoma cells were stable transfected to overexpress (sense construct) or underexpress (antisense construct) tissue factor. In vitro, there was no difference in plating efficiency or growth between these cell lines. In vivo, tumor cells transfected to overexpress tissue factor grew more rapidly, and established larger and more vascularized tumors than control transfectants. Antisense transfectants grew the slowest and were the least vascularized. Anticoagulation of mice with warfarin did not alter the difference between these tumor lines. Tumor cells over-expressing tissue factor released more (compared with control transfectants) mitogenic activity for endothelial cells in parallel with enhanced transcription of vascular permeability factor/vascular endothelial cell growth factor (VEGF/VPF), and diminished transcription of thrombospondin (TSP2), a molecule with anti-angiogenic properties. Antisense tissue factor transfectants, while releasing the lowest amount of mitogenic activity, had increased thrombospondin and decreased VEGF/VPF transcription compared with control transfectants or wild-type cells. Experiments with these sense, antisense, truncated sense, or vector tumor lines gave comparable results in complete medium, serum free medium or in the presence of hirudin, indicating that the activation of the coagulation mechanism was not likely to be responsible for changes in tumor cell properties. These results suggest that tissue factor regulates angiogenic properties of tumor cells by altering the production of growth regulatory molecules of endothelium by a mechanism distinct from tissue factor activation of the coagulation mechanism.
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PMID:Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. 752 87

Metastatic brain tumors are almost always associated with vasogenic brain edema, which in turn plays a pivotal role in the evolution of neurological morbidity associated with these lesions. Attention has recently focused on a group of proteinaceous vascular permeability factors (VPF's) that are capable of inducing angiogenesis and promoting increased capillary permeability. To test the hypothesis that metastatic brain tumors expressing VPF's are associated with peritumoral cerebral edema, a rabbit polyclonal immunoglobulin (Ig) G anti-VPF was used to immunostain pathological specimens of metastatic cerebral tumors obtained from 22 patients who underwent surgery at Yale-New Haven Hospital. Magnetic resonance (MR) imaging was used to correlate VPF staining in tumor tissue with the occurrence of peritumoral brain edema. A histological study of the microvasculature was then conducted by immunostaining the specimens for endothelial cell factor VIII surface antigen, using two gliosis specimens as controls. Results revealed 21 of 22 tumors stained positively for VPF's; the negative-VPF tumor was a melanoma that exhibited no peritumoral edema. Twenty of 22 tumors had MR imaging-evident vasogenic edema. The presence and intensity of VPF immunostaining of microvascular features were noted and compared. Factor VIII staining demonstrated tumor vascularity to be most abundant in VPF-rich regions of tumor. The authors therefore report a high correlation between the presence of VPF's and the occurrence of peritumoral brain edema associated with cerebral metastases.
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PMID:Vascular permeability factor in brain metastases: correlation with vasogenic brain edema and tumor angiogenesis. 752 34

Angiogenesis, the sprouting of capillaries from preexisting vessels, is of fundamental importance during embryonic development and is the principal process by which the brain and certain other organs become vascularized. Angiogenesis occurs during embryonic development but is almost absent in adult tissues. Transient and tightly controlled (physiological) angiogenesis in adult tissues occurs during the female reproductive cycle and during wound healing. In contrast, pathological angiogenesis is characterized by the persistent proliferation of endothelial cells, and is a prominent feature of diseases such as proliferative retinopathy, rheumathoid arthritis, and psoriasis. In addition, many tumors are able to attract blood vessels from neighbouring tissues. Tumor-induced angiogenesis requires a constitutive activation of endothelial cells. These endothelial cells dissolve their surrounding extracellular matrix, migrate toward the tumor, proliferate, and form a new vascular network, thus supplying the tumor with nutrients and oxygen and removing waste products. The onset of angiogenesis in human gliomas is characterized by the expression of genes encoding angiogenic growth factors such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) in tumor cells, and coordinate induction of genes in endothelial cells which encode the respective growth factor receptors. Developmental and tumor angiogenesis appear to be regulated by a paracrine mechanism involving VEGF and VEGF receptor-1 and -2.
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PMID:Molecular mechanisms of developmental and tumor angiogenesis. 752 60


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