RESUMEN
BACKGROUND: Induction of tolerance and minimizing the toxicity of immunosuppression are two fundamental goals in vascularized composite allotransplantation. Accumulating data indicate that triptolide is an agent that may have the capacity to suppress inflammation and immunologic rejection. METHODS: A heterotopic hindlimb allotransplantation model from Brown Norway to Lewis rats was established and treated with different doses of tacrolimus combined with or without triptolide. Mean survival time of the transplants was monitored, and histopathologic examination of the skin was performed. The level of inflammatory cytokine interleukin-1ß, interleukin-6, and tumor necrosis factor-á in peripheral blood was assayed. The percentage of T lymphocytes and its subsets was measured using flow cytometry. The level of recipient peripheral chimerism and the apoptosis of donor bone marrow cells were evaluated. The apoptotic related genes bcl-2 and Bax were detected by real-time polymerase chain reaction. RESULTS: The authors' results showed that triptolide not only reduces the dose of tacrolimus required for immunosuppression, but also decreased drug side effects in terms of weight gain and diarrhea. Triptolide had an obvious effect on proinflammatory cytokine expression and T-lymphocyte proliferation in the peripheral blood. Interestingly, triptolide could increase the mixed chimerism level of recipients, possibly by inhibiting the apoptosis of transplanted bone marrow cells by means of regulation of the apoptotic genes bcl-2 and Bax. CONCLUSIONS: Triptolide reduces the dose of tacrolimus required for immunosuppression by attenuating inflammation and by T-cell suppression. Furthermore, triptolide increases the chimerism level, which might contribute to acceptance of the allografts.
Asunto(s)
Quimerismo/efectos de los fármacos , Diterpenos/farmacología , Miembro Posterior/trasplante , Tolerancia Inmunológica/efectos de los fármacos , Inmunosupresores/farmacología , Fenantrenos/farmacología , Tacrolimus/administración & dosificación , Alotrasplante Compuesto Vascularizado , Animales , Apoptosis/efectos de los fármacos , Biomarcadores/metabolismo , Citocinas/metabolismo , Diterpenos/uso terapéutico , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Compuestos Epoxi/farmacología , Compuestos Epoxi/uso terapéutico , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Inmunosupresores/uso terapéutico , Masculino , Fenantrenos/uso terapéutico , Distribución Aleatoria , Ratas , Ratas Endogámicas Lew , Linfocitos T/metabolismo , Tacrolimus/uso terapéuticoRESUMEN
AIM: This study examined the correlation between P53 and vascular endothelial growth factor (VEGF) expression together with tumour vascularity and investigated their clinical significance in the prognosis of gastric carcinoma. SUBJECTS AND METHODS: Ninety-five patients with gastric carcinoma who underwent curative surgical resection were studied using immunohistochemical staining. Correlation between the expression of p53, VEGF, microvessel count (MVC) and various clinicopathologic factors were studied. RESULTS: No significant correlation was found between p53 expression and clinicopathologic factors. The rate of VEGF positivity was significantly higher in patients with haematogenous metastasis than in those without haematogenous metastasis. Both p53 and VEGF expression were associated with MVC. The MVC in p53 positive tumours was significantly higher than that in p53 negative tumours. Similarly, the same trend was seen between VEGF expression and MVC. The p53 and VEGF were co-expressed in 61 of 95 tumours (64.2%), and a significant (p < 0.01) association between p53 and VEGF expressions was demonstrated. The rate of VEGF positivity was significantly (p < 0.01) higher in the patients with disease recurrence than in those without recurrence, whereas no significant correlation was found between disease recurrence and the expression of p53. CONCLUSIONS: The p53 expression may play an important role in controlling angiogenesis by regulating VEGF expression and VEGF expression is associated closely with disease recurrence. In addition, both p53 and VEGF expression might be useful in indicating the prognosis in patients with gastric carcinoma.
OBJETIVO: Este estudio examinó la correlación entre el P53 y la expresión del factor de crecimiento del endotelio vascular (VEGF) junto con las vascularidad del tumor, e investigó su importancia clínica en la prognosis del carcinoma gástrico. SUJETOS Y MÉTODOS: Noventa y nueve pacientes con carcinoma gástrico que fueron sometidos a resección quirúrgica curativa, fueron estudiados usando teñido inmunohistoquímico. Se estudió la correlación entre la expresión de p53, VEGF, el conteo de microvasos (MVC) y varios factores clínico-patológicos. RESULTADOS: No se halló una correlación significativa entre la expresión de p53 y los factores clínico-patológicos. La tasa de positividad de VEGF, fue significativamente más alta en pacientes con metástasis hematogénica que en pacientes sin metástasis hematogénica. Tanto la expresión de p53 como la de VEGF estuvieron asociadas con el conteo MVC. El MVC en tumores p53 positivos fue significativamente más alto que en tumores p53 negativos. De manera similar, la misma tendencia se observó entre la expresión de VEGF y MVC. El p53 y el VEGA fueron co-expresados en 61 de 95 tumores (64.2%), y se demostró una asociación significativa (p < 0.01) entre las expresiones de p53 y VEGA. La tasa de positividad VEGA fue significativamente más alta (p < 0.01) en los pacientes con recurrencia de la enfermedad que en aquellos sin recurrencia, en tanto que no se halló una correlación significativa entre la recurrencia de la enfermedad y la expresión de p53. CONCLUSIONES: La expresión p53 puede desempeñar un importante papel en el control de la angiogénesis mediante la regulación de la expresión de VEGF y la expresión de VEGF está estrechamente asociada con la recurrencia de la enfermedad. Además, tanto la expresión de p53 como la de VEGF podrían ser útiles para indicar la prognosis de pacientes con carcinoma gástrico.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Neoplasias Gástricas/metabolismo , /metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Estudios de Cohortes , Microvasos , Pronóstico , Neoplasias Gástricas/irrigación sanguíneaRESUMEN
AIM: This study examined the correlation between P53 and vascular endothelial growth factor (VEGF) expression together with tumour vascularity and investigated their clinical significance in the prognosis of gastric carcinoma. SUBJECTS AND METHODS: Ninety-five patients with gastric carcinoma who underwent curative surgical resection were studied using immunohistochemical staining. Correlation between the expression of p53, VEGF microvessel count (MVC) and various clinicopathologic factors were studied. RESULTS: No significant correlation was found between p53 expression and clinicopathologic factors. The rate of VEGF positivity was significantly higher in patients with haematogenous metastasis than in those without haematogenous metastasis. Both p53 and VEGF expression were associated with MVC. The MVC in p53 positive tumours was significantly higher than that in p53 negative tumours. Similarly, the same trend was seen between VEGF expression and MVC. The p53 and VEGF were co-expressed in 61 of 95 tumours (64.2%), and a significant (p < 0.01) association between p53 and VEGF expressions was demonstrated. The rate of VEGF positivity was significantly (p < 0.01) higher in the patients with disease recurrence than in those without recurrence, whereas no significant correlation was found between disease recurrence and the expression of p53. CONCLUSIONS: The p53 expression may play an important role in controlling angiogenesis by regulating VEGF expression and VEGF expression is associated closely with disease recurrence. In addition, both p53 and VEGF expression might be useful in indicating the prognosis in patients with gastric carcinoma.