RESUMEN
Angiogenesis is essential for development, growth and advancement of solid tumours. Interferon-gamma-inducible protein 10 (IP-10) regulates lymphocyte chemotaxis, mediates vascular pericyte proliferation and acts as an angiostatic agent, thus inhibiting tumour growth. This prompted us to study the clinical implications of IP-10 expression related to angiogenesis in uterine cervical cancers. The levels of IP-10 decreased with advancement, and the prognosis of the 30 patients with low IP-10 expression in uterine cervical cancers was poor (66%), whereas the 24-month survival rate of the other patients with high IP-10 expression was 90%. Furthermore, IP-10 levels significantly reverse-correlated with vascular endothelial growth factor (VEGF) levels in uterine cervical cancers. Interferon-gamma-inducible protein 10 might work on suppression of angiogenesis associated with VEGF in advancement, and can be recognised as a prognostic indicator. Furthermore, IP-10 activation might be effective on the suppression of regrowth or recurrence after intensive treatment for advanced cervical cancers.
Asunto(s)
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Quimiocinas CXC/genética , Neovascularización Patológica/genética , Neoplasias del Cuello Uterino/genética , Adenocarcinoma/irrigación sanguínea , Adenocarcinoma/patología , Adulto , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/irrigación sanguínea , Carcinoma de Células Escamosas/patología , Quimiocina CXCL10 , Quimiocinas CXC/metabolismo , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , Persona de Mediana Edad , Neovascularización Patológica/metabolismo , Análisis de Supervivencia , Neoplasias del Cuello Uterino/irrigación sanguínea , Neoplasias del Cuello Uterino/patología , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Angiogenesis is essential for development, growth and advancement of solid tumors. Cyclooxygenase (cox)-2 is recognized as an angiogenic factor in various tumors. This prompted us to study the clinical implications of cox-2 expression and angiogenesis in uterine endometrial cancers. PATIENTS AND METHODS: Fifty patients underwent curative resection for uterine endometrial cancers. In uterine endometrial cancers, cox-2 levels were determined by enzyme immunoassay, and the localization and counts of microvessels were determined by immunohistochemistry. RESULTS: There was a significant correlation between microvessel counts and cox-2 levels in uterine endometrial cancers. Cox-2 localized in the cancer cells, but not in the stromal cells of uterine endometrial cancer tissues. Cox-2 levels decreased with the advancement. Furthermore, cox-2 levels significantly correlated with VEGF levels in uterine endometrial cancers. CONCLUSIONS: VEGF associated with cox-2 might work on angiogenesis at an early status in growth. Therefore, long-term administration of cox-2 inhibitors might be effective in the suppression of recurrent initiation of uterine endometrial cancers after curative resection.
Asunto(s)
Neoplasias Endometriales/irrigación sanguínea , Neoplasias Endometriales/enzimología , Neovascularización Patológica , Prostaglandina-Endoperóxido Sintasas/biosíntesis , Factor A de Crecimiento Endotelial Vascular/análisis , Adulto , Anciano , Ciclooxigenasa 2 , Neoplasias Endometriales/cirugía , Femenino , Regulación de la Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Inmunohistoquímica , Proteínas de la Membrana , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Prostaglandina-Endoperóxido Sintasas/farmacologíaRESUMEN
Vascular endothelial cell growth factor (VEGF)-C levels were significantly (P<0.05) increased in 24 out of 40 metastatic lymph node lesions of uterine cervical cancers. The prognosis of the 24 patients with increased VEGF-C level in metastatic lymph node lesions was poor and the 24-month survival rate was 38%, while the rate of the 16 patients with no change in VEGF-C level in metastatic lymph node lesions was 81%. There was a significant (P<0.01) difference in the 24-month survival rates between the two groups. This is novel, direct evidence that VEGF-C might contribute to the aggressive lymphangitic metastasis in uterine cervical cancers, and that the increase in VEGF-C level from primary tumour to metastatic lymph node might be a prognostic indicator.
Asunto(s)
Metástasis Linfática/diagnóstico , Neoplasias del Cuello Uterino/patología , Factor C de Crecimiento Endotelial Vascular/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Técnicas para Inmunoenzimas , Inmunohistoquímica , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Sensibilidad y Especificidad , Análisis de Supervivencia , Neoplasias del Cuello Uterino/cirugíaAsunto(s)
Neoplasias Endometriales/metabolismo , Neoplasias Ováricas/metabolismo , Receptores de Estrógenos/metabolismo , Receptor alfa de Estrógeno , Receptor beta de Estrógeno , Femenino , Humanos , ARN Mensajero/metabolismo , ARN Neoplásico/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Angiogenesis is essential for development, growth and advancement of solid tumors. ETS-1 has been recognized as a candidate for tumor angiogenic transcription factor. This prompted us to study the clinical implications of ETS-1-related angiogenesis in uterine cervical cancers. PATIENTS AND METHODS: Fifty patients underwent curative resection for uterine cervical cancers. The patients' prognoses were analyzed with a 24-month survival rate. In the tissue of 60 uterine cervical cancers, the levels of ets-1 mRNA, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF) and interleukin (IL)-8 were determined by competitive reverse transcription-polymerase chain reaction using recombinant RNA and enzyme immunoassay, and the localization and counts of microvessels were determined by immunohistochemistry. RESULTS: There was a significant correlation between microvessel counts and ets-1 gene expression levels in uterine cervical cancers. Immunohistochemical staining revealed that the localization of ETS-1 was similar to that of vascular endothelial cells. The level of ets-1 mRNA correlated with the levels of PD-ECGF and IL-8 among angiogenic factors. Furthermore, the prognosis of the 25 patients with high ets-1 mRNA expression in uterine cervical cancers was extremely poor, while the 24-month survival rate of the other 25 patients with low ets-1 mRNA expression was 92%. CONCLUSIONS: ETS-1 might be a prognostic indicator as an angiogenic mediator in uterine cervical cancers.
Asunto(s)
ADN de Neoplasias/genética , Regulación de la Expresión Génica , Neovascularización Patológica , Proteínas Proto-Oncogénicas/biosíntesis , Factores de Transcripción/biosíntesis , Neoplasias del Cuello Uterino/irrigación sanguínea , Neoplasias del Cuello Uterino/genética , Adulto , Anciano , Anciano de 80 o más Años , Cartilla de ADN , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Pronóstico , Proteína Proto-Oncogénica c-ets-1 , Proteínas Proto-Oncogénicas c-ets , ARN Mensajero/análisis , Sobrevida , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugíaRESUMEN
BACKGROUND: Angiogenesis is essential for development, growth and advancement of solid tumors. During angiogenesis, ETS-1 is strongly expressed in vascular endothelial cells and the adjacent interstitial cells, while the inhibition of ETS-1 expression leads to suppression of angiogenesis. This prompted us to study the clinical implications of ETS-1 in relation to angiogenesis in uterine endometrial cancers. PATIENTS AND METHODS: Sixty patients underwent resection for uterine endometrial cancers. From the tissues of 60 uterine endometrial cancers, the levels of ets-1 mRNA, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF) and interleukin (IL)-8 were determined by competitive RT-PCR using recombinant RNA and enzyme immunoassay, and the localization and counts of microvessel were determined by immunohistochemistry. RESULTS: There was a significant correlation between microvessel count and ets-1 gene expression levels in uterine endometrial cancers. Immunohistochemical staining revealed that the localization of ETS-1 was similar to that of vascular endothelial cells. The level of ets-1 mRNA tended to increase with increasing disease stage. Furthermore, the level of ets-1 mRNA correlated with levels of VEGF in well-differentiated adenocarcinomas (G1) and of bFGF in moderately differentiated adenocarcinomas (G2) and poorly differentiated adenocarcinomas (G3). CONCLUSIONS: ETS-1 is a possible angiogenic mediator in uterine endometrial cancers.
Asunto(s)
Adenocarcinoma/irrigación sanguínea , Adenocarcinoma/genética , ADN de Neoplasias/genética , Neoplasias Endometriales/irrigación sanguínea , Neoplasias Endometriales/genética , Regulación Neoplásica de la Expresión Génica , Neovascularización Patológica , Proteínas Proto-Oncogénicas/biosíntesis , Factores de Transcripción/biosíntesis , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Cartilla de ADN , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Factores de Crecimiento Endotelial/biosíntesis , Femenino , Humanos , Inmunohistoquímica , Péptidos y Proteínas de Señalización Intercelular/biosíntesis , Interleucina-8/biosíntesis , Linfocinas/biosíntesis , Persona de Mediana Edad , Proteína Proto-Oncogénica c-ets-1 , Proteínas Proto-Oncogénicas c-ets , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
BACKGROUND: Angiogenesis is essential for development, growth and advancement of solid tumors. The tumor-associated macrophage has been recognized among inflammatory cells as a candidate for supplying tumor angiogenic factors. Interleukin (IL)-8 is assumed to be a macrophage-derived mediator of angiogenesis. This prompted us to study the clinical implications of macrophage-derived angiogenesis in uterine endometrial cancers. PATIENTS AND METHODS: Sixty patients underwent curative resection for uterine endometrial cancers. The patient prognosis was analyzed with a 48 month survival rate after curative resection. In tissue of uterine endometrial cancers, the levels of IL-1alpha, IL-1beta, tumor necrosis factor-alpha, IL-8, basic fibroblast growth factor, vascular endothelial growth factor and platelet-derived endothelial cell growth factor were determined by enzyme immunoassay, and the localization and counts of microvessels and macrophages were determined by immunohistochemistry. RESULTS: There was a significant correlation between microvessel counts and IL-8 levels and between infiltrated macrophage counts and IL-8 levels in uterine endometrial cancers. Immunohistochemical staining revealed that the localization of IL-8 was similar to that of CD68 for macrophages. IL-8 levels were significantly increased during myometrial invasion from stage Ia to stages Ib through IV. CONCLUSIONS: IL-8 might act as an angiogenic switch in myometrial invasion in stage I uterine endometrial cancers. Furthermore, IL-8 supplied from infiltrated macrophages within and around the tumor might not be a prognostic indicator of advancement, but may be associated with myometrial invasion in uterine endometrial cancers.
Asunto(s)
Neoplasias Endometriales/irrigación sanguínea , Interleucina-8/metabolismo , Miometrio/patología , Neovascularización Patológica/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Citocinas/metabolismo , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Femenino , Sustancias de Crecimiento/metabolismo , Humanos , Técnicas para Inmunoenzimas , Macrófagos/metabolismo , Persona de Mediana Edad , Invasividad Neoplásica , Proteínas de Neoplasias/metabolismo , Neovascularización Patológica/patología , Pronóstico , Tasa de SupervivenciaRESUMEN
Ginsenoside-Rb2 derived from ginseng inhibited invasiveness to the basement membrane of endometrial cancer cell lines Ishikawa. HHUA and HEC-1-A cells. These cells dominantly expressed matrix metalloproteinase (MMP)-2 (gelatinase A) among MMPs by zymography. Ginsenoside-Rb2 suppressed the expression and activity of MMP-2, but did not alter the expression of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in the cells. Therefore, ginsenoside-Rb2 might inhibit invasiveness to the basement membrane via MMP-2 suppression in some endometrial cancers, and can be used as a medicine for inhibition of secondary spreading of uterine endometrial cancers.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/patología , Ginsenósidos , Metaloproteinasa 2 de la Matriz/metabolismo , Saponinas/farmacología , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Membrana Basal/efectos de los fármacos , Western Blotting , Neoplasias Endometriales/enzimología , Femenino , Humanos , Técnicas para Inmunoenzimas , Inhibidores de la Metaloproteinasa de la Matriz , Invasividad Neoplásica , Células Tumorales CultivadasRESUMEN
The relative overexpression of estrogen receptor (ER)-alpha exon 5 splicing variant, the disrupted synchronization of ER-beta and ER-alpha expressions, and the suppression of progesterone receptor (PR) form A expression as a transcriptional repressor might be related to metastatic potential of uterine endometrial cancers, leading to poor patient prognosis related to estrogen refractoriness.