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

Hemangiomas, localized tumors of blood vessels, appear in approximately 10-12% of Caucasian infants. These lesions are characterized by a rapid proliferation of capillaries for the first year (proliferating phase), followed by slow, inevitable, regression of the tumor over the ensuing 1-5 yr (involuting phase), and continual improvement until 6-12 yr of age (involuted phase). To delineate the clinically observed growth phases of hemangiomas at a cellular level, we undertook an immunohistochemical analysis using nine independent markers. The proliferating phase was defined by high expression of proliferating cell nuclear antigen, type IV collagenase, and vascular endothelial growth factor. Elevated expression of the tissue inhibitor of metalloproteinase, TIMP 1, an inhibitor of new blood vessel formation, was observed exclusively in the involuting phase. High expression of basic fibroblast growth factor (bFGF) and urokinase was present in the proliferating and involuting phases. There was coexpression of bFGF and endothelial phenotypic markers CD31 and von Willebrand factor in the proliferating phase. These results provide an objective basis for staging hemangiomas and may be used to evaluate pharmacological agents, such as corticosteroids and interferon alfa-2a, which accelerate regression of hemangiomas. By contrast, vascular malformations do not express proliferating cell nuclear antigen, vascular endothelial growth factor, bFGF, type IV collagenase, and urokinase. These data demonstrate immunohistochemical differences between proliferating hemangiomas and vascular malformations which reflect the biological distinctions between these vascular lesions.
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PMID:Cellular markers that distinguish the phases of hemangioma during infancy and childhood. 791 Nov 27

Over the last decade, much has been learned about the genetic changes that occur in human neoplasia and how they contribute to the neoplastic state. Oncogenes and tumor suppressor genes have been identified, and many powerful molecular genetic techniques have emerged. Brain tumors have been intensively studied as part of this process. Specific and recurring genetic alterations have been identified and are associated with specific tumor types. In astrocytomas, for example, losses of genetic material on chromosomes 10 and 17 and amplification of the epidermal growth factor receptor gene seem important in pathogenesis, with the loss of chromosome 10 and the amplification of epidermal growth factor receptor being strongly associated with glioblastoma multiforme. Meningiomas, on the other hand, have usually lost part or all of chromosome 22. Brain tumors also express growth factors and growth factor receptors that may be important in promoting tumor growth and angiogenesis. These include epidermal growth factor, transforming growth factor-alpha, platelet-derived growth factor, the fibroblast growth factors, and vascular endothelial growth factor. In this article, we review the genetic aberrations that occur in the major types of brain tumors, including glial tumors, meningiomas, acoustic neuromas, medulloblastomas, primitive neuroectodermal tumors, and pituitary tumors. Wherever possible, clinical correlations have been made concerning the prognostic and therapeutic implications of specific aberrations. We also provide some background about the cytogenetic and molecular genetic techniques that have contributed to the description and understanding of these alterations and speculate as to some clinical and basic science issues that might be explored in the future.
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PMID:Genetic aberrations in human brain tumors. 800 71

Angiogenesis is a major new prognostic factor in breast cancer. Small vessels quantitatively assessed by staining with anti-CD31 antibodies correlate with lymph node involvement and are a better independent predictor of survival. There are many vascular growth factors, but predominant in primary tumors assessed by nuclease protection assays are vascular endothelial growth factor and platelet-derived endothelial cell growth factor. Acidic and basic fibroblast growth factor are also detectable. A common feature of these angiogenic factors is heparin binding, so novel analogues of suramin that can compete for heparin binding have been developed. These are more potent in vitro against endothelial cells and are less toxic in vivo, thereby giving a much better therapeutic ratio. Protein kinase C is also important in endothelial growth, as it is in carcinoma growth. Thus, a novel agent inhibiting this pathway, and inducing transforming growth factor-beta production has been assessed in a Phase I trial; this agent is bryostatin. It does not cause marrow suppression and has stimulatory effects of tumor necrosis factor-alpha and interleukin (IL)-6 production. High expression of epidermal growth factor (EGF) receptors and erbB-2 has been related to poor prognosis. EGF receptors are mainly regulated by transcription, as are some cases of high erbB-2 expression. Thus, a novel approach to gene therapy is being developed using direct tumor injection of cDNA, with a tumor specific promoter ligated to the IL-2 gene. This avoids many problems associated with targeting. Because IL-2 stimulation of cytotoxic T-cells will depend on appropriate antigen presentation, human lymphocyte antigen Class I expression was studied, as was the peptide transporter system RING4 (TAP1). Losses were found in 50% of cases, and in some cases only in lymph nodes but not primary cancers, thereby providing evidence for a role in suppressing metastasis. Thus, many new approaches to therapy are possible as a result of understanding growth factors and intracellular signaling pathways.
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PMID:Gene therapy through signal transduction pathways and angiogenic growth factors as therapeutic targets in breast cancer. 803 35

Many tumor cells produce vascular endothelial growth factor (VEGF), which is thought to be a pivotal mediator of tumor neoangiogenesis. Expression of the VEGF gene can be induced by tumor promoting phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), which activate protein kinase C (PKC). Here we show that in transient transfection assays a mutated form of the murine p53 tumor suppressor gene (ala135-->val) induces expression of VEGF mRNA and potentiates TPA stimulated VEGF mRNA expression. In NIH 3T3 cells which stably overexpress the temperature sensitive p53 (ala135-->val), displaying mutant phenotype at 37 degrees C and wildtype phenotype at 32.5 degrees C, induction of VEGF mRNA and protein by activated PKC is strongly synergistic with mutant, but not wildtype p53. Mutant p53 specifically increases TPA induction of VEGF without affecting the expression of other TPA inducible genes. TPA dependent VEGF expression is also enhanced by human p53 mutated at amino acid 175. Thus, our data link PKC and p53, the gene most frequently altered in human tumors, with the regulation of tumor angiogenesis.
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PMID:Mutant p53 potentiates protein kinase C induction of vascular endothelial growth factor expression. 810 42

Vascular permeability factor (VPF), also known as vascular endothelial growth factor, is a secreted protein implicated in tumor-associated microvascular hyperpermeability and angiogenesis. Tumor cells in 11 of 12 renal cell carcinomas expressed high levels of VPF messenger RNA (mRNA) by in situ hybridization, the only exception being a case of the relatively avascular papillary variant. Expression was further accentuated adjacent to areas of necrosis. Both tumor cells and endothelial cells in small vessels adjacent to tumor stained strongly for VPF protein by immunohistochemistry. Endothelial cells did not express detectable VPF mRNA, but did express high levels of mRNA for the VPF receptors flt-1 and KDR indicating that the endothelial cell staining likely reflects binding of VPF secreted by adjacent tumor cells. Three transitional cell carcinomas also labeled strongly for VPF mRNA. These data suggest an important role for VPF in the vascular biology of these two common human malignancies.
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PMID:Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. 823 42

Epithelial ovarian cancer is an aggressive malignancy with a generally poor outcome. To improve survival, novel therapeutic strategies for this disease are needed and require elucidation of the biological events that underlie transformation and tumor growth. Vascular permeability factor (VPF), also known as vascular endothelial growth factor, is a homodimeric glycoprotein that acts on vascular endothelium as a potent permeability-inducing agent and mitogen. The present study demonstrates for the first time the constitutive gene expression of VPF in normal and neoplastic human ovaries. Abundant levels of VPF have been identified by an immunoassay in the ascites of patients with epithelial ovarian cancer (K-T. Yeo et al., Cancer Res., 53: 2912-2918, 1993). We have identified the malignant epithelium as one source of VPF in the ascites. Reverse transcription-polymerase chain reaction has demonstrated the expression of the two secreted isoforms, VPF121 and VPF165, in normal and neoplastic ovaries. Western blotting and an endothelial cell proliferation assay confirmed secretion of a biologically active product. VPF may be an important mediator of ascites formation and tumor metastasis observed in neoplastic conditions of the ovary.
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PMID:Vascular permeability factor gene expression in normal and neoplastic human ovaries. 826 52

Vascular permeability factor, or vascular endothelial growth factor (VPF/VEGF) is a disulfide-linked dimeric glycoprotein of about 40 kD that promotes fluid and protein leakage from blood vessels. Various human tumor cell lines and cells including fetal vascular smooth muscle cells produce VPF/VEGF. Since glomerular mesangial cells (MC) are closely related to vascular smooth muscle cells, we examined whether cultured human MC produce VPF/VEGF. Northern blotting analysis revealed that cultured human MC expressed a 3.7 kilobases (kb) VPF/VEGF mRNA. Human peripheral blood mononuclear cells (PBMC) also expressed VPF/VEGF transcripts of 8.6 and 3.8 kb. Although the sizes of the transcripts suggested the existence of unique molecular species of VPF/VEGF mRNA in PBMC, RT-PCR analysis revealed that PBMC as well as human MC expressed 121, 165, and 189 amino acid-containing isoforms of VPF/VEGF, implying that there are no unique alternative splicing products of VPF/VEGF mRNA in PBMC. Fetal calf serum and 12-o-tetradecanoyl- phorbol-13-acetate (TPA) transiently enhanced VPF/VEGF mRNA expression in cultured human MC. Transforming growth factor-beta 1 enhanced VPF/VEGF mRNA expression in cultured human MC at least within 24 hours. Dexamethasone (DEX) inhibited the TPA-induced increase in VPF/VEGF mRNA expression, whereas DEX did not change the basal level. The DEX depressed the TPA-induced increase in VPF/VEGF mRNA expression is therefore probably a result of transcriptional control. VPF/VEGF protein was detected in cultured human MC with immunoperoxidase staining using anti-VPF/VEGF antibody. TPA increased VPF/VEGF protein levels as well as those of VPF/VEGF mRNA in cultured human MC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human mesangial cells and peripheral blood mononuclear cells produce vascular permeability factor. 826 55

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a multifunctional cytokine expressed and secreted at high levels by many tumor cells of animal and human origin. As secreted by tumor cells, VPF/VEGF is a 34-42 kDa heparin-binding, dimeric, disulfide-bonded glycoprotein that acts directly on endothelial cells (EC) by way of specific receptors to activate phospholipase C and induce [Ca2+]i transients. Two high affinity VPF/VEGF receptors, both tyrosine kinases, have thus far been described. VPF/VEGF is likely to have a number of important roles in tumor biology related, but not limited to, the process of tumor angiogenesis. As a potent permeability factor, VPF/VEGF promotes extravasation of plasma fibrinogen, leading to fibrin deposition which alters the tumor extracellular matrix. This matrix promotes the ingrowth of macrophages, fibroblasts, and endothelial cells. Moreover, VPF/VEGF is a selective endothelial cell (EC) growth factor in vitro, and it presumably stimulates EC proliferation in vivo. Furthermore, VPF/VEGF has been found in animal and human tumor effusions by immunoassay and by functional assays and very likely accounts for the induction of malignant ascites. In addition to its role in tumors, VPF/VEGF has recently been found to have a role in wound healing and its expression by activated macrophages suggests that it probably also participates in certain types of chronic inflammation. VPF/VEGF is expressed in normal development and in certain normal adult organs, notably kidney, heart, adrenal gland and lung. Its functions in normal adult tissues are under investigation.
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PMID:Vascular permeability factor (VPF, VEGF) in tumor biology. 828 15

Expression of the vascular permeability factor/vascular endothelial growth factor (VEGPF) gene was investigated in human central nervous system (CNS) neoplasms and normal brain. Adsorption of capillary permeability activity from human glioblastoma multiforme (GBM) cell conditioned medium and GBM cyst fluids by anti-VEGPF antibodies demonstrated that VEGPF is secreted by GBM cells and is present in sufficient quantities in vivo to induce vascular permeability. Cloning and sequencing of polymerase chain reaction-amplified GBM and normal brain cDNA demonstrated three forms of the VEGPF coding region (567, 495, and 363 nucleotides), corresponding to mature polypeptides of 189, 165, and 121 amino acids, respectively. VEGPF mRNA levels in CNS tumors vs. normal brain were investigated by the RNase protection assay. Significant elevation of VEGPF gene expression was observed in 81% (22/27) of the highly vascular and edema-associated CNS neoplasms (6/8 GBM, 8/8 capillary hemangioblastomas, 6/7 meningiomas, and 2/4 cerebral metastases). In contrast, only 13% (2/15) of those CNS tumors that are not commonly associated with significant neovascularity or cerebral edema (2/10 pituitary adenomas and 0/5 nonastrocytic gliomas) had significantly increased levels of VEGPF mRNA. The relative abundance of the forms of VEGPF mRNA was consistent in tumor and normal brain: VEGPF495 > VEGPF363 > VEGPF567. In situ hybridization confirmed the presence of VEGPF mRNA in tumor cells and its increased abundance in capillary hemangioblastomas. Our results suggest a significant role for VEGPF in the development of CNS tumor neovascularity and peritumoral edema.
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PMID:Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms. 838 Aug 10

Polyoma virus middle T-transformed murine endothelioma cell lines provide a useful model for studying vascular lesions such as hemangiomas, hemangiosarcomas, and Kaposi's sarcoma and tumor-associated angiogenesis. In vivo they produce fast-growing, hemorrhaging, cavernous blood-filled hemangiomas, mainly formed by recruited host endothelial cells, suggesting an angiogenesis-like process underlying the lesion. The molecular mechanism(s) responsible for the recruitment of host endothelial cells by endothelioma cells has not yet been identified. We found that five different cultured endothelioma cell lines produced a soluble factor, named endothelioma-derived motility factor (EDMF) that stimulates chemotaxis (motility induced by a gradient of soluble attractant), haptotaxis (motility in response to substrate-bound attractant), and chemoinvasion (migration through a layer of reconstituted basement membrane, Matrigel) of normal human, bovine, and murine endothelial cells. The inhibitory effect of actinomycin D and of enzymatic treatment on its activity proved that EDMF is a protein. EDMF binds to heparin, since its activity was inhibited by heparin, and it was retained on a heparin-Sepharose column. Its molecular weight, as assessed by Sephacryl S-200 gel filtration, ranges from 40,000-65,000. Although in many aspects EDMF is similar to vascular permeability factor-vascular endothelial growth factor, this was not detected in endothelioma cell supernatants, as assessed by enzyme-linked immunosorbent assay, thus indicating that EDMF might be related to, but is not identical with, vascular permeability factor. Our findings support the notion that recruitment of host endothelial cells by endothelioma cells in vivo might be mediated by a still unidentified, soluble factor that stimulates and directs endothelial cell migration.
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PMID:Endothelial cell migration and invasiveness are induced by a soluble factor produced by murine endothelioma cells transformed by polyoma virus middle T oncogene. 839 82


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