ABSTRACT
Objective To investigate the change of HepG2 liver tumor perfusion after microbubble enhanced ultrasound cavitation treatment and observe the related pathological injury.Methods Twenty eight Balb/c(nu/nu) nude mice transplanted subcutaneous HepG2 tumor were divided into three groups randomly,including the microbubble enhanced ultrasound cavitation group,the ultrasound group and the sham group.Microbubble enhanced ultrasound cavitation treatment was performed by 0.1 ml microbubbles intravenous injection combined with pulse ultrasound emission in experimental group,while in control groups only ultrasound exposure or microbubble injection were applied.The perfusion of tumors was imaged using contrast-enhanced ultrasonography before and after treatments.Time-intensity curve and peak intensity were analyzed.The tumors were then harvested for histological examination.Results The perfusion of HepG2 tumors almost vanished immediately after treatment in experimental group,with the peak intensity reduced from (26.9 ± 10.9)％ to(8.2 ± 5.8)％ (P ＜0.05).There was no significant changes before and after treatments (P ＞ 0.05) in the two control groups.Histological findings were disruption of the endothelia,significant hemorrhage and increased intercellular fluid.Conclusions Microbubble-enhanced ultrasound cavitation can significantly reduce tumor blood perfusion and disrupt tumor vascularture.This new ultrasound therapy can potentially become a new physical anti-angiogenetic therapy for liver tumor.
ABSTRACT
Correlação da expressão do receptor do fator de crescimento do epitélio vascular - vascular endothelial growth factor (VEGF) e do KI-67, em pacientes com câncer de mama, com variáveis histopatológicas. Introdução: proteínas que influam na proliferação celular, como o VEGF e o KI-67, são alvo de estudos. O VEGF está implicado na angiogênese, que é necessária ao crescimento tumoral. Objetivo: Analisar a correlação do VEGF e do KI-67 com variáveis histopatológicas. Métodos: entre 15/03/2008 e 14/0412009, incluímos 41 pacientes com câncer de mama inicial, rumores T1 e T2, para estudo, usando a coloração H & E na análise do tumor, grau histológico e invasão vascular e a imunoperoxidade para a avaliação imuno-histoquímica com anticorpos específicos para os receptores de VEGF, KI-67, p53 e receptor de estrogênio (RE), usando escore qualitativo até 3+ na avaliação da intensidade da coloração e/ou quantitativo até 5+, para avaliar a expressão percentual das células coradas. O escore total, soma das duas, pode chegar ao máximo de 8+. Apenas o KI-67 foi categorizado pelo percentual de células coradas na IHQ e considerado positivo a partir de 20%. Resultados: O receptor do VEGFR1, tanto no escore intensidade de cor quanto no escore total, apresenta correlação positiva com os tumores T1 (p=.01), com o receptor estrogênico positivo (p=.01) e com a expressão negativa do KI-67 (p=.02). A expressão do KI-67 apresenta correlação positiva com p53 (p=.00) e com o receptor hormonal negativo (RE-) (p=.04) e correlação fraca com a invasão vascular (p=.09) e o grau histológico indiferenciado (G3) (p=.07). Discussão: A avaliação de marcadores tumorais que possam responder à terapia alvo é um objetivo a ser perseguido. A correlação positiva do VEGF com o status do RE ja foi relatada e está de acordo com nossos resultados. A expressão do KI-67 é associada à pobre evento. Os resultados controversos dos marcadores refletem a dificuldade em padronizar as avaliações (reagentes)...
Correlation of the expression of the receptor of vascular endothelial growth factor (VEGP) and KI-67 with pathological variables in breast cancer patients. Background: Many studies have been conducted on proteins that have action on cell proliferation, such as VEGP and KI-67. VEGP acts in the angiogenesis required for tumor growth. The KI-67 correlates with proliferation of tumor cells, probably reflecting its aggressiveness. Objective: To analyze the correlation of VEGPR1 and KI-67 with pathological variables. Methods: The study was approved by the Committee on Ethics in research, University Hospital of Porto Alegre (RS). Between March 2008 and April 2009 we included 41 patients with early breast cancer (T1 and T2). We used H & E staining for tumor analysis, histological grade and vascular invasion, and immunohistochemistry evaluation with antibodies specific for VEGP receptors, KI-67, p53, estrogen receptor (ER), using quality score until 3+ of the evaluation of intensity of stain and quantitative untiI 5+, to evaluate the expression percentage of stained cells. The total score, add either, can reach 8+ Only the KI-67 was categorized by percentage of stained cells in the IHC and considered positive above 20%. Statistics: correlation and pearson's chi square and, for the significant variables, used the multivariate analysis. Results: The receptor VEGPR1 in both color intensity score and the total score, correlated positively with T1 tumors (p=.01), with the estrogen receptor positive (p=.01) and negative expression of KI-67 (p=.02). The expression of KI-67 correlates positively with p53 (p=.00) and with estrogen receptor negative (p=.04) and weak correlation with vascular invasion (p=.09) and histological grade undifferentiated (p=.07). Discussion: evaluation of tumor markers that may respond to targeted therapy is a goal to be pursued. The positive correlation of VEGP with the status of ER has been reported and is consistent with our results...
Subject(s)
Humans , Female , Immunohistochemistry , /metabolism , Breast Neoplasms/diagnosis , Neovascularization, Pathologic/diagnosis , Biomarkers, Tumor/metabolism , Breast Neoplasms/pathology , PrognosisABSTRACT
OBJETIVOS: Avaliar a ação do bevacizumabe subconjuntival em modelo experimental de neovascularização em córnea de coelho. Analisar se o modelo de avaliação empregado é adequado e comparar entre os grupos a extensão dos vasos, inflamação e re-epitelização da córnea. MÉTODOS: Estudo experimental, prospectivo em 20 coelhos submetidos a trauma químico com hidróxido de sódio a 1 N divididos em dois grupos, Imediatamente após a queimadura, o grupo tratado recebeu injeção subconjuntival de 0,15 ml (3,75 mg) de bevacizumabe e o grupo controle, injeção subconjuntival de 0,15 ml de soro fisiológico a 0,9 por cento. Após 25 dias, foi realizada análise fotográfica digital para avaliar a extensão e inflamação/calibre dos vasos segundo critério pré-estabelecido e estudo histopatológico da córnea, no qual foi avaliado o estado do epitélio e o número de polimorfonucleares. RESULTADOS: A extensão dos neovasos corneanos foi menor no grupo estudo em relação ao controle (p<0,001). Não houve diferença significativa entre os grupos na inflamação/calibre dos vasos. A análise histopatológica mostrou que não ocorreu diferença entre os grupos nas variáveis estado do epitélio e número de polimorfonucleares. A análise de concordância para a variável extensão dos vasos e para a variável inflamação/calibre dos vasos teve uma estimativa do coeficiente de Kappa respectivamente de 0,705 e 0,500 indicando bom grau de concordância nas diferentes avaliações cegadas, validando o método empregado. CONCLUSÕES: O modelo de avaliação foi adequado e pode ser reproduzido para avaliar outras drogas na córnea. O bevacizumabe inibiu a neovascularização corneana, porém não foi eficaz em reduzir o processo inflamatório. A droga não atrasou a re-epitelização da córnea.
PURPOSES: To evaluate the effect of subconjunctival bevacizumab in an experimental model of neovascularization in rabbit cornea. Determine its effect on vessels extension, inflammation, epithelialization of the cornea and whether the evaluation method used is appropriate to compare neovascular models. METHODS: Experimental, prospective, randomized, blinded study in twenty rabbits subjected to chemical trauma with sodium hydroxide at 1N divided into two groups. The study group received subconjunctival injection of 0.15 ml (3.75 mg) of bevacizumab and was compared with the control group that received subconjunctival injection of 0.15 ml saline solution. After 25 days, digital photographic analysis was performed to assess the vessel's extension and inflammation/diameter according to pre-established criteria. Histopathology of the cornea, which evaluated the state of the epithelium and the number of polymorphonuclear cells was also studied. RESULTS: The length of the neovessels was greater in the control group compared to the study group (P=<0.001). There was no difference in inflammation/vessel diameter between groups. Histopathology analysis showed that there was no difference between groups for the variables state of the epithelium and number of polymorphonuclear cells. The concordance analysis for the variable extension of the vessels and the variable inflammation/vessel diameter was estimated with Kappa coefficients of 0.705 and 0.500 respectively, indicating a good level of agreement in different evaluations and validating the method. CONCLUSIONS: The experimental model is adequate and can be reproduced to evaluate other drugs in the cornea. Bevacizumab inhibit the neovessels' growth but was not effective in preventing the inflammatory response. The drug did not delay the reepithelialization of the cornea.
Subject(s)
Animals , Male , Rabbits , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal/therapeutic use , Burns, Chemical/drug therapy , Corneal Neovascularization/prevention & control , Burns, Chemical/complications , Burns, Chemical/pathology , Corneal Neovascularization/etiology , Corneal Neovascularization/pathology , Disease Models, Animal , Prospective Studies , Random AllocationABSTRACT
Objective To investigate the expression of endostatin (ES) in rat peritoneum and its association with peritoneal neoangiogensis. Methods Thirty-two male SD rats were randomly divided into 4 groups: normal control rats (C group), renal failure without PD rats (non-PD group), rats dialyzed with 1.5% PD solution (1.5% PD group) and 4.25% PD solution (4.25% PD group). After regular PD for 28 days, mRNA and protein expression of ES in peritoneal tissues of each group were detected by RT-PCR and immunohistochemistry respectively. Microvessel density (MVD) of peritoneal tissue was assessed using immunohistochemistry with CD34 monoclonal antibody. Results ES mRNA was expressed in each group, 0.47±0.05 in C group, 0.45±0.04 in non-PD group, 0.46±0.04 in 1.5%PD group, 0.47±0.03 in 4.25%PD group, and no significant differences were found among groups. Score of ES protein expression was O in C group, 2 in non-PD group, 4 in 1.5%PD group, and 9 in 4.25%PD group. MVD was 3.13±1.13 in C group, 5.13±1.14 in non-PD group, 9.00±1.51 in 1.5%PD group, 10.75±1.83 in 4.25%PD group, and significant differences were found among groups. Conclusion Uremia circumstance and non-physiological compatibility peritoneal dialysate can increase ES protein expression and MVD, which may participate in and have effects on the course of peritoneal neoangiogensis.
ABSTRACT
0.05).Three days after interventional therapy,the values of BF,BV,MTT,PS,MVD and VEGF of VX_2 tumors in interventional group were (7.5?2.4)ml? 100g~(-1)?min~(-1),(1.20?0.23)ml/100g,(3.29?0.57)s,(4.0?1.5)ml?100g~(-1)?min~(-1), 16.0?2.4/HP and 0.215?0.008 respectively.Compared with the values of pre-interventional therapy and the control group,there were significant differences among them(P0.7,P0.05)but had a significant negative correlation with average A value of VEGF(r=-0.78,P