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1.
Cerebrovasc Dis ; 49(5): 462-473, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877893

RESUMO

BACKGROUND: Hemangioma (Hem) is a benign tumor commonly seen in infancy with a relative high morbidity. Human umbilical vein endothelial cell (HUVEC)-derived extracellular vesicles (EVs) are actively participated in Hem. Therefore, this study is designed to figure out the underlying mechanism of HUVEC-derived EVs in Hem. METHODS: Initially, EVs were separated from HUVECs and identified. HUVEC-derived EVs in normoxia or hypoxia were then cultivated with Hem endothelial cells (HemECs) to test the proliferation, apoptosis, and migration of HemECs. Microarray analysis was performed to select microRNAs (miRs) with differential expression. miR-210 in hypoxia-induced HUVECs was silenced, and the relevant EVs were extracted and then co-cultured with HemECs to perform biological effect experiments. Then, the target relation between miR-210 and homeobox A9 (HOXA9) was identified by the dual luciferase reporter gene assay and RNA immunoprecipitation assay. Moreover, xenograft transplantation was also applied to confirm the in vitro experiments. RESULTS: Hypoxia-induced HUVECs promoted release of EVs, which were absorbed by HemECs. Hypoxia-induced HUVEC-EVs promoted HemEC proliferation and migration and inhibited apoptosis. miR-210 from the hypoxia-induced HUVEC-EVs was highly expressed and promoted HemEC growth. Silencing miR-210 expression in the hypoxia-induced HUVEC-EVs suppresses Hem development in vivo. In addition, miR-210 targeted HOXA9. CONCLUSION: Silencing miR-210 in HUVEC-derived EVs could suppress Hem by targeting HOXA9. This investigation may provide novel insights for Hem treatment.


Assuntos
Vesículas Extracelulares/transplante , Hemangioma/prevenção & controle , Células Endoteliais da Veia Umbilical Humana/transplante , MicroRNAs/genética , Interferência de RNA , Animais , Apoptose , Hipóxia Celular , Movimento Celular , Proliferação de Células , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Feminino , Hemangioma/genética , Hemangioma/metabolismo , Hemangioma/patologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lactente , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Carga Tumoral , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Arch Biochem Biophys ; 688: 108404, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32416101

RESUMO

Hemangioma (HA) is the most common benign tumor and formed by the proliferating endothelial cells of blood vessels. Interleukins (ILs) have been reported to be critical for HA progression. Our present study found that the expression of IL-10 was decreased in HA cells and tissues as compared to their corresponding controls. Treatment with recombinant IL-10 (rIL-10) can suppress the proliferation of HA cells via suppression of proliferating cell nuclear antigen (PCNA), while over expression of PCNA can attenuate rIL-10-inhibited cell proliferation. Further, rIL-10 can decrease the promoter activity and mRNA stability of PCNA in HA cells. Mechanistically, rIL-10 can increase expression of miR-27b-3p to decrease mRNA stability of PCNA, while down regulation of YY1 is involved in rIL-10 suppressed transcription of PCNA. Collectively, IL-10 can suppress the expression of PCNA via miR-27b-3p mediated suppression of mRNA stability and YY1 mediated down regulation of transcription. It suggested that rIL-10 might be a potential therapeutic approach for HA development and progression.


Assuntos
Células Endoteliais/metabolismo , Hemangioma/prevenção & controle , Interleucina-10/farmacologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proliferação de Células/fisiologia , Progressão da Doença , Hemangioma/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Interleucina-10/metabolismo , MicroRNAs/metabolismo , Antígeno Nuclear de Célula em Proliferação/genética , Estabilidade de RNA/efeitos dos fármacos , RNA Mensageiro/metabolismo , Fator de Transcrição YY1/metabolismo
3.
FASEB J ; 33(9): 10505-10514, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31242765

RESUMO

Hemangioblastoma (HB) is an abnormal intracranial buildup of blood vessels that exhibit a great potential for hemorrhage. Surgical options are limited, and few medications are available for treatment. We show here by immunohistochemical analysis that HB lesions display highly increased levels of VEGF expression and macrophage/microglia infiltration compared with those in normal brain tissues. In the meantime, TNF superfamily 15 (TNFSF15) (also known as vascular endothelial growth inhibitor), an antiangiogenic cytokine, is highly expressed in normal brain blood vessels but diminished in HB lesions. We set up a brain hemangioma model by using mouse bEnd.3 cells of a T antigen-transformed endothelial cell line that produce a large amount of VEGF. When implanted in mouse brains, these cells form lesions that closely resemble the pathologic characteristics of HB. Retroviral infection of bEnd.3 cells with TNFSF15 leads to inhibition of VEGF production and retardation of hemangioma formation. Similar results are obtained when wild-type bEnd.3 cells are implanted in the brains of transgenic mice overexpressing TNFSF15. Additionally, TNFSF15 treatment results in enhanced pericyte coverage of the blood vessels in the lesions together with reduced inflammatory cell infiltration and decreased hemorrhage. These findings indicate that the ability of TNFSF15 to counterbalance the abnormally highly angiogenic and inflammatory potential of the microenvironment of HB is of therapeutic value for the treatment of this disease.-Yang, G.-L., Han, Z., Xiong, J., Wang, S., Wei, H., Qin, T.-T., Xiao, H., Liu, Y., Xu, L.-X., Qi, J.-W., Zhang, Z.-S., Jiang, R., Zhang, J., Li, L.-Y. Inhibition of intracranial hemangioma growth and hemorrhage by TNFSF15.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Modelos Animais de Doenças , Células Endoteliais/transplante , Hemangioma/prevenção & controle , Hemorragias Intracranianas/prevenção & controle , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Animais , Apoptose , Proliferação de Células , Células Endoteliais/citologia , Hemangioma/metabolismo , Hemangioma/patologia , Humanos , Hemorragias Intracranianas/metabolismo , Hemorragias Intracranianas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Prognóstico , Células Tumorais Cultivadas , Microambiente Tumoral , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/administração & dosagem
4.
Biomed Pharmacother ; 111: 236-243, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30584986

RESUMO

Hemangioma (HA) is one of the commonest benign vascular neoplasms of infancy. Inhibitor of differentiation 1 (ID-1) has been reported to be an oncogene in multiple cancers. However, the role of ID-1 and its molecular mechanism in HA progression have not been elucidated. In the present study, we found that ID-1 expression at mRNA and protein levels was up-regulated in HA-derived endothelial cells (HDECs). Knockdown of ID-1 inhibited proliferation, facilitated apoptosis, and enhanced propranolol cytotoxicity in HDECs. Knockdown of ID-1 decreased the protein levels of phospholyrated protein kinase-B (Akt) and phospholyrated mammalian target of rapamycin (mTOR). Inhibition of PI3K/Akt/mTOR pathway by LY294002 abrogated ID-1-mediated pro-proliferation and anti-apoptosis effects in HDECs. In conclusion, knockdown of ID-1 suppressed proliferation and promoted apoptosis by inactivating phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling in HDECs, shedding light on the function of ID-1 in HA progression and highlighting the therapeutic value of ID-1 for HA.


Assuntos
Proliferação de Células/fisiologia , Hemangioma/metabolismo , Proteína 1 Inibidora de Diferenciação/deficiência , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Apoptose/fisiologia , Células Endoteliais/metabolismo , Técnicas de Silenciamento de Genes/métodos , Hemangioma/prevenção & controle , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Proteína 1 Inibidora de Diferenciação/genética , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/antagonistas & inibidores
6.
Rev. centroam. obstet. ginecol ; 21(2): 47-50, abr.-jun. 2016. ilus
Artigo em Espanhol | LILACS | ID: biblio-869635

RESUMO

El corioangioma es el tumor benigno más frecuente de la placenta con una incidencia de 1%. Usualmente son asintomáticos y muchos pasan desapercibidos. Los tumores grandes pueden causar complicaciones maternas y fetales graves por lo que es importante realizar diagnóstico prenatal temprano. El pronóstico de un embarazo con corioangioma gigante de placenta, depende fundamentalmente del tamaño y de la detección oportuna.


Assuntos
Humanos , Feminino , Doenças Placentárias , Hemangioma/complicações , Hemangioma/prevenção & controle , Neoplasias Uterinas/complicações
7.
Actas dermo-sifiliogr. (Ed. impr.) ; 107(4): 284-293, mayo 2016. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-151608

RESUMO

El avance en el conocimiento de la biología y la terapéutica de las anomalías vasculares (AV) han hecho que sean un motivo frecuente de consulta en las consultas de dermatología en la actualidad, y que se hayan creado unidades multidisciplinares para el abordaje de los pacientes con AV complejas. Aunque el diagnóstico de la mayoría de las AV es clínico, a menudo su estudio completo requiere pruebas complementarias de imagen para determinar su naturaleza, extensión y pronóstico. La primera prueba de imagen que se solicita por su rapidez e inocuidad es la ecografía (US). En esta revisión se busca resumir y actualizar los conceptos clave en la ecografía de las AV para su mejor comprensión para los clínicos o especialistas en imagen que tratan a estos pacientes


Advances in our understanding of the biology and therapy of vascular anomalies have made this condition a common reason for consulting a dermatologist. In addition, multidisciplinary units have been created to manage patients with complex vascular anomalies. Although most vascular anomalies are diagnosed based on clinical findings, a thorough evaluation often requires additional imaging tests to determine the nature, extension, and prognosis of these lesions. Because it is fast and noninvasive, ultrasound is usually the first imaging test ordered. In the present review, we provide a state-of-the-art synthesis of key concepts in the ultrasound examination of vascular anomalies so that they are more accessible to clinicians and medical imaging specialists involved in the management of these lesions


Assuntos
Humanos , Masculino , Feminino , Ultrassonografia/instrumentação , Ultrassonografia/métodos , Ultrassonografia/tendências , Doenças Vasculares/complicações , Doenças Vasculares/diagnóstico , Doenças Vasculares/patologia , Hemangioma/prevenção & controle , Hemangioma , Dermatologia/instrumentação , Dermatologia/métodos , Hemodinâmica/fisiologia , Ultrassonografia Doppler/instrumentação , Ultrassonografia Doppler/métodos , Ultrassonografia Doppler/tendências , Lesões do Sistema Vascular/diagnóstico , Lesões do Sistema Vascular/prevenção & controle , Lesões do Sistema Vascular , Neoplasias de Tecido Vascular/complicações , Neoplasias de Tecido Vascular/prevenção & controle , Neoplasias de Tecido Vascular
8.
Oncotarget ; 6(28): 25660-76, 2015 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-26308070

RESUMO

Hemangioma is a benign vascular neoplasm of unknown etiology. In this study, we generated an endothelial-specific PyMT gene-expressing transgenic mouse model that spontaneously develops hemangioma. Based on this transgenic model, a specific binding between PyMT and the core AC dimer of protein phosphatase 2A (PP2A) was verified in hemangioma vascular endothelial cells. The binding between PyMT and the PP2A AC dimer resulted in dissociation of the B subunit from the PP2A complex and inactivation of PP2A phosphatases, which in turn activated AKT and ERK signaling and promoted cell proliferation, migration and angiogenesis in vitro and tumorigenesis in vivo. Consistent with the in vitro findings, decreased PP2A phosphatase activity and disruption of the PP2A heterotrimeric complex were also observed in both primary transgene-positive TG(+) mouse hemangioma endothelial cells (TG(+) HEC cells) and human proliferating phase hemangioma endothelial (human HEC-P) cells, but not in transgene-negative TG(-) mouse normal vascular endothelial cells (TG(-) NEC cells) and human involuting phase hemangioma endothelial (human HEC-I) cells. Further, it was observed that in human hemangioma cells, endoglin could compete with the PP2A/A, C subunits for binding to the PP2A/B subunit, thereby resulting in dissociation of the B subunit from the PP2A complex. Treatment of Tie2/PyMT transgenic mice with the PP2A activator FTY720 significantly delayed the occurrence of hemangioma. Our data provide evidence of a previously unreported anti-proliferation and anti-angiogenesis effect of PP2A in vascular endothelial cells, and show the therapeutic value of PP2A activators in hemangioma.


Assuntos
Proliferação de Células , Células Endoteliais/enzimologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hemangioma/enzimologia , Neoplasias Experimentais/enzimologia , Neovascularização Patológica , Proteína Fosfatase 2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Antígenos Transformantes de Poliomavirus/genética , Antígenos Transformantes de Poliomavirus/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Ativação Enzimática , Ativadores de Enzimas/farmacologia , Cloridrato de Fingolimode/farmacologia , Hemangioma/genética , Hemangioma/patologia , Hemangioma/prevenção & controle , Humanos , Camundongos Endogâmicos C57BL , Camundongos Nus , Camundongos Transgênicos , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Neoplasias Experimentais/prevenção & controle , Fosforilação , Multimerização Proteica , Interferência de RNA , Transdução de Sinais , Transfecção
10.
Arch Dis Child Fetal Neonatal Ed ; 98(2): F108-11, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22611112

RESUMO

BACKGROUND: Infantile haemangioma (IH) is the most commonly observed tumour in children. Off-label pharmacological treatment of IH with the beta-blocker propranolol induces regression of IH. Based on the fact that IH are more frequently observed in premature babies than in mature babies and the evidence that beta-blocker therapy leads to regression of IH, the authors generated the hypothesis that the use of ß-2-sympathomimetics during pregnancy for inhibiting premature labour might increase occurrence of IH in preterm infants. METHODS: For group comparison t test, Mann-Whitney U test and Fisher's exact test were used. Logistic regression was carried out by the forward stepwise method with Wald statistics. RESULTS: Data of 328 preterm infants (<32 gestational weeks) or with a birth weight of less than 1500 g (<36 gestational weeks) born between January 2006 and December 2008 were analysed. A total of 15 were excluded due do death within the 1st month of life, 38 because of lost to follow-up and six due to incomplete data. Complete data of 269 preterm infants were retrospectively analysed. During the follow-up period of median 1.6 years, 50 infants developed one or more IH within their first 6 months of life. IH occurred in 40/181 patients with intrauterine exposure to the ß-2-sympathomimetic hexoprenaline and in 10/88 without exposure (OR=4.3; 95% CI 1.4 to 13.8). Furthermore, the influence of antenatal exposure to glucocorticosteroids for induction of lung development was analysed. Prenatally exposed subjects showed reduced occurrence of IH (OR=0.2; 95% CI 0.05 to 0.8). CONCLUSION: Intrauterine exposure to the ß-2-sympathomimetic hexoprenaline might increase the occurrence of IH in preterm infants.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Hemangioma/induzido quimicamente , Hexoprenalina/efeitos adversos , Doenças do Prematuro/induzido quimicamente , Tocolíticos/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Hemangioma/prevenção & controle , Hexoprenalina/uso terapêutico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/prevenção & controle , Masculino , Troca Materno-Fetal , Trabalho de Parto Prematuro/prevenção & controle , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Estudos Retrospectivos , Tocólise/efeitos adversos , Tocolíticos/uso terapêutico
11.
Asuncion; IPS/UCA; 00002009. 42 p. (Hemangioma renal como causa de hematuria a propòsito de un caso).
Monografia em Espanhol | LILACS, BDNPAR | ID: biblio-1018670

RESUMO

La pràctica ambulatoria asume hoy un papel protagònico en el sistema de salud.


Assuntos
Hemangioma/complicações , Hemangioma/congênito , Hemangioma/prevenção & controle , Hemangioma/sangue , Paraguai
12.
Genes Chromosomes Cancer ; 42(3): 213-27, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15578690

RESUMO

Tuberous sclerosis complex (TSC) is a familial tumor disorder for which there is no effective medical therapy. Disease-causing mutations in the TSC1 or TSC2 gene lead to increased mammalian target of rapamycin (mTOR) kinase activity in the conserved mTOR signaling pathway, which regulates nutrient uptake, cell growth, and protein translation. The normal function of TSC1 and TSC2 gene products is to form a complex that reduces mTOR kinase activity. Thus, mTOR kinase inhibition may be a useful targeted therapeutic approach. Elevated interferon-gamma (IFN-gamma) expression is associated with decreased severity of kidney tumors in TSC patients and mouse models; therefore, IFN-gamma also has therapeutic potential. We studied cohorts of Tsc2+/- mice and a novel mouse model of Tsc2-null tumors in order to evaluate the efficacy of targeted therapy for TSC. We found that treatment with either an mTOR kinase inhibitor (CCI-779, a rapamycin analog) or with IFN-gamma reduced the severity of TSC-related disease without significant toxicity. These results constitute definitive preclinical data that justify proceeding with clinical trials using these agents in selected patients with TSC and related disorders.


Assuntos
Modelos Animais de Doenças , Interferon gama/uso terapêutico , Proteínas Repressoras/fisiologia , Sirolimo/análogos & derivados , Sirolimo/uso terapêutico , Esclerose Tuberosa/tratamento farmacológico , Proteínas Supressoras de Tumor/fisiologia , Animais , Cistadenoma/metabolismo , Cistadenoma/patologia , Cistadenoma/prevenção & controle , Quimioterapia Combinada , Hemangioma/metabolismo , Hemangioma/patologia , Hemangioma/prevenção & controle , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Neoplasias Renais/prevenção & controle , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Neoplasias Hepáticas Experimentais/prevenção & controle , Camundongos , Camundongos Knockout , Camundongos Nus , Fosforilação , Proteínas Quinases/metabolismo , Proteínas Repressoras/genética , Proteínas Quinases S6 Ribossômicas/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR , Esclerose Tuberosa/metabolismo , Esclerose Tuberosa/patologia , Proteína 2 do Complexo Esclerose Tuberosa , Proteínas Supressoras de Tumor/genética
13.
@rq. otorrinolaringol ; 8(3): 244-248, set. 2004. ilus
Artigo em Português | LILACS | ID: lil-417126

RESUMO

O hemangiopericitmoa é um tumor raro, de origem vascular, responsável por 1% de todos os tumores vasculares. Entretanto, uma parcela impotante deste tumor incide na região da cabeça e pescoço.


Assuntos
Humanos , Feminino , Hemangiopericitoma , Hemangioma/prevenção & controle , Neoplasias dos Seios Paranasais , Seio Esfenoidal , Seios Paranasais
14.
Verh K Acad Geneeskd Belg ; 64(3): 197-224, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12238243

RESUMO

Hemangiomas represent the most frequent tumors of infancy. However, the pathogenesis of these tumors is still largely unknown, and current treatment of juvenile hemangiomas remains unsatisfactory. We have presented a novel animal model for hemangiomas. Induction of hemangioma development was achieved by intraperitoneal (i.p.) infection of 4-day-old rats with the mouse polyoma virus (PyV). This led to the development of multiple hemangiomas, which caused death of the untreated animals within 3 weeks p.i. The hemangiomas had the histological and immunohistochemical features reminiscent of human hemangiomas. Moreover, the angiogenesis inhibitor TNP-470 afforded a protective effect in this model. Tumor growth is determined by the balance between cell proliferation and apoptosis and is modulated by angiogenesis. Angiogenesis is a complex process, involving extensive interplay between cells, extracellular matrix components and soluble factors. Each of these factors represents a possible target for pharmacological intervention to inhibit blood vessel formation and subsequently tumor growth. We have focused on specific inhibitors of the angiogenesis inducers basic fibroblast growth factor and Thymidine Phosphorylase and studied their mechanism of action and anti-angiogenic activity. In addition, we have shown that the apoptosis-inducer cidofovir inhibits PyV-induced hemangioma development in rats and the growth of virus-independent, vascular tumors in mice. So far, cidofovir has only been evaluated clinically for the treatment of human papillomavirus (HPV)-associated tumors. Our findings open new perspectives for the use of cidofovir as an anti-tumor agent in the therapy of hemangiomas and other tumors that are not associated with an oncogenic virus.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Apoptose , Citosina/análogos & derivados , Hemangioma/prevenção & controle , Neovascularização Patológica , Organofosfonatos , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Divisão Celular , Cidofovir , Cicloexanos , Citosina/farmacologia , Citosina/uso terapêutico , Modelos Animais de Doenças , Fator 2 de Crescimento de Fibroblastos/antagonistas & inibidores , Substâncias de Crescimento , Hemangioma/irrigação sanguínea , Hemangioma/patologia , Humanos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/prevenção & controle , O-(Cloroacetilcarbamoil)fumagilol , Compostos Organofosforados/farmacologia , Compostos Organofosforados/uso terapêutico , Ratos , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Timidina Fosforilase/antagonistas & inibidores , Infecções Tumorais por Vírus/prevenção & controle
15.
Int J Cancer ; 91(2): 241-7, 2001 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11146452

RESUMO

Inhibitors of proteases prevent tumor-associated matrix degradation, affecting tumor growth, angiogenesis and metastasis. Our study was designed to investigate the effect of inhibition of matrix metalloproteinases (MMPs) on the growth of experimental hemangiomas, using the model of murine endothelioma eEnd.1 cells. In nude mice, these cells generate hemangiomas, consisting mostly of host-recruited endothelial cells, whose growth requires the activity of MMPs. In vitro, eEnd.1 cells produce factors that recruit endothelial cells and stimulate them to release MMPs. Over-expression of TIMP-2, following retrovirus-mediated gene transfer, decreased tumor growth in vivo. The infected clone CR1, which produces high levels of TIMP-2 (as assessed by Northern blot, ELISA and reverse zymography), formed slow-growing tumors that did not grow beyond 0.4 g, while clone 1H, which produces little TIMP-2, grew not dissimilarly to mock-infected cells and parental e.End.1 cells. Histologically, control tumors presented the features of cavernous hemangiomas, while CR1 tumors had a more solid pattern, showing foci of apoptotic cells. In vitro, TIMP-2 over-expression had no autocrine anti-proliferative effect on endothelioma cells but reduced their ability to recruit endothelial cells. CR1 cells lacked the capacity of mock-infected or parental eEnd.1 cells to stimulate endothelial cell motility and invasiveness. Antibodies against TIMP-2 restored the ability of CR1 to induce endothelial cell invasion. We conclude that, in this model, genetic increase of TIMP-2 inhibits tumor growth, apparently by affecting the recruitment and organization of host endothelial cells by the transformed cells.


Assuntos
Hemangioma/prevenção & controle , Inibidores de Metaloproteinases de Matriz , Inibidor Tecidual de Metaloproteinase-2/biossíntese , Animais , Células Cultivadas , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Hemangioma/metabolismo , Hemangioma/patologia , Humanos , Camundongos , Camundongos Nus , Invasividade Neoplásica , RNA Mensageiro/análise , Inibidor Tecidual de Metaloproteinase-2/genética
16.
Cancer Res ; 59(10): 2376-83, 1999 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-10344747

RESUMO

Hemangiomas represent the most frequent tumors of infancy. However, the pathogenesis of these tumors is still largely unknown, and current treatment of juvenile hemangiomas remains unsatisfactory. Here we present a novel animal model to study proliferating hemangiomas and to evaluate the effect of angiostatic compounds on their growth. Intraperitoneal (i.p.) infection of 4-day-old rats with murine polyomavirus resulted in the development of multiple cutaneous, intramuscular (i.m.), and cerebral hemangiomas with 100% frequency. Histological examination of the brain revealed the formation of immature lesions as soon as 4 days postinfection (p.i.). The subsequent exponential growth of the hemangiomas, both in number and size, was associated with severe hemorrhage and anemia. The cerebral, cutaneous, and i.m. lesions consisted of blood-filled cysts, histologically similar to human cavernous hemangiomas and stained positive for proliferating cell nuclear antigen, urokinase-type plasminogen activator, and vascular endothelial growth factor. Mature cerebral hemangiomas also expressed von Willebrand factor. Cerebral lesions caused death of the untreated animals within 19.2 +/- 1.1 days p.i. Remarkably fewer and smaller hemangiomas developed in animals that had been treated s.c. with the angiogenesis inhibitor TNP-470. Accordingly, TNP-470 (50 mg/kg), administered twice a week from 3 days p.i., significantly delayed tumor-associated mortality [mean day of death, 28.2 +/- 3.3 (P < 0.001)]. Even if therapy was initiated when cerebral hemangiomas were already macroscopically visible (i.e., 9 days p.i.), a significant delay in hemangioma-associated mortality was observed. Also, the IFN-inducer polyinosinic-polycytidylic acid caused a delay of 9 days (P < 0.005) in tumor-associated mortality when administered i.p. at 5 mg/kg, twice a week, starting at day 3 p.i. The model described here may be useful for investigating (a) the angiogenic mechanism(s) underlying hemangioma progression; and (b) the effect of anti-angiogenic compounds on vascular tumor growth.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/prevenção & controle , Transformação Celular Viral , Modelos Animais de Doenças , Hemangioma/prevenção & controle , Neovascularização Patológica/tratamento farmacológico , Infecções por Polyomavirus/tratamento farmacológico , Polyomavirus/patogenicidade , Sesquiterpenos/uso terapêutico , Infecções Tumorais por Vírus/tratamento farmacológico , Animais , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/virologia , Cicloexanos , Progressão da Doença , Endotélio Vascular/efeitos dos fármacos , Feminino , Hemangioma/tratamento farmacológico , Hemangioma/etiologia , Hemangioma/virologia , Humanos , Lactente , Recém-Nascido , Injeções Subcutâneas , Indutores de Interferon/uso terapêutico , Masculino , O-(Cloroacetilcarbamoil)fumagilol , Poli I-C/uso terapêutico , Ratos , Fatores Sexuais , Carga Viral
17.
Pediatr Dev Pathol ; 2(3): 264-9, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10191350

RESUMO

The nomenclature and occurrence of chorangioma of the placenta are reviewed here. Recurrence of multiple chorangiomas has been described, but it is apparently an uncommon or underreported event. There is a strong relationship between placental chorangiomas and gestation at high altitude, suggesting the occurrence of vascular growth factors induced by hypoxia. Fluid transitions may exist between chorangioma, chorangiomatosis, and chorangiosis, although the latter is common in diabetic pregnancies, whereas chorangiomas are not so correlated.


Assuntos
Córion/irrigação sanguínea , Hemangioma/patologia , Doenças Placentárias/patologia , Altitude , Síndrome de Beckwith-Wiedemann/patologia , Doenças em Gêmeos , Feminino , Hemangioma/classificação , Hemangioma/epidemiologia , Hemangioma/prevenção & controle , Humanos , Incidência , Gravidez , Recidiva
18.
Cancer Res ; 57(23): 5277-80, 1997 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-9393749

RESUMO

Angiostatin inhibits angiogenesis and metastatic tumor growth; however, its usefulness in treating primary nonmetastasizing tumors is less well understood. We now report the effectiveness of human angiostatin administration in a mouse hemangioendothelioma model. Human angiostatin was administered to mice with s.c. hemangioendothelioma and associated disseminated intravascular coagulopathy (Kasabach-Merritt syndrome). Angiostatin significantly reduced tumor volume in comparison to nontreated controls, increased survival, and prevented the profound thrombocytopenia and anemia of Kasabach-Merritt syndrome. Apoptosis of tumor cells was induced by angiostatin, but tumor cell proliferation was not inhibited. These data suggest angiostatin as a novel treatment for nonmetastasizing vascular tumors and for Kasabach-Merritt syndrome.


Assuntos
Anemia/prevenção & controle , Antineoplásicos/uso terapêutico , Hemangioendotelioma/tratamento farmacológico , Hemangioendotelioma/patologia , Hemangioma/prevenção & controle , Fragmentos de Peptídeos/uso terapêutico , Plasminogênio/uso terapêutico , Trombocitopenia/prevenção & controle , Angiostatinas , Animais , Apoptose/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Feminino , Humanos , Camundongos , Camundongos Nus , Fragmentos de Peptídeos/biossíntese , Plasminogênio/biossíntese , Baço/efeitos dos fármacos , Baço/patologia , Síndrome
19.
J Med Syst ; 17(3-4): 133-7, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7504718

RESUMO

Thirty-nine cases of hepatocellular carcinoma (HCC) out of 55,135 examinees were examined. The diagnostic problems of ultrasonography (US) in detecting HCC and the risk value of 10 factors in HCC were discussed. We also propose the surveillance programs for HCC in Multiphasic Health Testing and Services (MHTS). US will be performed at 3-, or 6 monthly intervals in conjunction with AFP monitoring for the examinees over 50 males and over seventy females with liver dysfunction (GOT > 38 IU/ml) is recommended.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/instrumentação , Neoplasias Hepáticas/diagnóstico por imagem , Ultrassonografia/instrumentação , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/prevenção & controle , Diagnóstico Diferencial , Feminino , Hemangioma/sangue , Hemangioma/diagnóstico por imagem , Hemangioma/prevenção & controle , Humanos , Japão , Testes de Função Hepática , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/prevenção & controle , Masculino , Pessoa de Meia-Idade , Triagem Multifásica/instrumentação , Fatores de Risco , alfa-Fetoproteínas/metabolismo
20.
Nutr Cancer ; 10(3): 119-28, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-3628036

RESUMO

The effect of feeding 0.02% retinyl acetate on the development of cryptogenic neoplasms and the life span of C3H/HeJ (+) mice of both sexes was studied. The survival at 105 weeks was 58% in untreated males and 28% in untreated females vs. 39% in treated males and 14% in treated females. The average weight in treated groups was also 10-15% lower. The incidence (percent) of neoplasm-bearing animals and total neoplasms was 87% and 57, respectively, in female controls vs. 93% and 55 in treated females. In male controls, these values were 57% and 39 compared with 50% and 38 in treated males. In treated animals, there was no reduction in the most common neoplasms, that is, neoplasms of the mammary gland and liver. The numbers of ovarian neoplasms and lung adenomas were slightly lower. Therefore, retinyl acetate exerted, at best, only a slight inhibitory effect on development of some types of cryptogenic neoplasms in mice.


Assuntos
Longevidade/efeitos dos fármacos , Neoplasias Experimentais/prevenção & controle , Vitamina A/análogos & derivados , Animais , Peso Corporal , Diterpenos , Feminino , Hemangioma/induzido quimicamente , Hemangioma/prevenção & controle , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/prevenção & controle , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/prevenção & controle , Masculino , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/prevenção & controle , Camundongos , Camundongos Endogâmicos C3H , Neoplasias Ovarianas/induzido quimicamente , Neoplasias Ovarianas/prevenção & controle , Vitamina A/farmacologia , Vitamina A/uso terapêutico , Vitamina A/toxicidade
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