RESUMEN
BACKGROUND: MicroRNA (miRNA)-126 (miR-126) is an endothelial-specific miRNA located within intron 7 of epidermal growth factor-like domain 7 (EGFL7). However, the role of miR-126 in cancer is controversial. METHODS: We examined the function of miR-126 in oral squamous cell carcinoma (OSCC) cells. Furthermore, a series of 118 cases with OSCC were evaluated for the expression levels of miR-126. RESULTS: MicroRNA-126 (miR-126) was associated with cell growth and regulation of vascular endothelial growth factor-A activity, and demethylation treatment increased expression levels of miR-126 and EGFL7 in OSCC cells. A significant association was found between miR-126 expression and tumour progression, nodal metastasis, vessel density, or poor prognosis in OSCC cases. In the multivariate analysis, decreased miR-126 expression was strongly correlated with disease-free survival. CONCLUSION: The present results suggest that miR-126 might be a useful diagnostic and therapeutic target in OSCC.
Asunto(s)
Carcinoma de Células Escamosas/genética , Linfangiogénesis/genética , MicroARNs/metabolismo , Neoplasias de la Boca/genética , Neovascularización Patológica/genética , Factor A de Crecimiento Endotelial Vascular/genética , Anciano , Anciano de 80 o más Años , Proteínas de Unión al Calcio , Línea Celular Tumoral , Supervivencia sin Enfermedad , Regulación hacia Abajo , Familia de Proteínas EGF , Factores de Crecimiento Endotelial/genética , Femenino , Humanos , Masculino , MicroARNs/antagonistas & inhibidores , Persona de Mediana Edad , Activación TranscripcionalRESUMEN
As part of a collaborative effort to evaluate whether effects on male reproductive organs of chemicals can be detected within two-week in toxicity studies, eight-week-old male Sprague-Dawley rats were given a single oral administration of 100 mg/kg of Cyclophosphamide (Cp), and sacrificed at 1, 3, 7 and 14 days thereafter. The numbers of seminiferous epithelial cells were counted in the seminiferous tubules of stages II-III, V, VII and XII of the spermatogenic cycle. Animals showed decreased spermatogonia at Day 3, decreased spermatogonia and preleptotene spermatocytes at Day 7, and decreased spermatogonia and zygotene spermatocytes at Day 14. We also detected decrease of zygotene spermatocytes on careful routine/traditional histopathological examination at Day 14. These results suggest that the testicular toxicity of Cp can be detected within two weeks after treatment with a sufficient dose in rats.
Asunto(s)
Antineoplásicos/toxicidad , Ciclofosfamida/toxicidad , Inmunosupresores/toxicidad , Testículo/efectos de los fármacos , Administración Oral , Animales , Antineoplásicos/administración & dosificación , Peso Corporal/efectos de los fármacos , Recuento de Células , Ciclofosfamida/administración & dosificación , Ingestión de Alimentos/efectos de los fármacos , Inmunosupresores/administración & dosificación , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Epitelio Seminífero/efectos de los fármacos , Epitelio Seminífero/patología , Espermatogénesis/efectos de los fármacos , Testículo/patología , Testículo/fisiopatología , Factores de Tiempo , Pruebas de ToxicidadRESUMEN
OBJECTIVES: The role of Regenerating (Reg) IV on peritoneal metastasis was examined in gastric cancer using. MATERIAL AND METHODS: Reg IV-transfected human gastric cancer cells (MKN28-R1, MKN28-R2, TMK1-R1), control transfectants (MKN28-R0, TMK1-R0), and REG4-knocked down MKN45 cells were examined in in vitro and in nude mice peritoneal metastasis models. RESULTS AND DISCUSSION: Increase of expression and secretion of Reg IV, and levels of BCL-2, BCL-XL,survivin, phosphorylated AKT, and phosphorylated EGFR, and decrease of nitric oxide-induced apoptosis were found in Reg IV-transfectants, whereas those were abrogated in the knockdown cells. In mice models, increased number and size of peritoneal tumors and decreased apoptosis were found in Reg IV-transfectants, whereas those were abrogated by the knockdown cells. Mice survivals were worsened in Reg IV-transfectants-inoculated mice, but were improved in Reg IV-knockdown cell-inoculated mice. Levels of Reg IV protein in peritoneal lavage fluids increased in Reg IV-transfectants inoculated mice, but decreased in Reg IV-knockdown cell inoculated mice. In metastasized human gastric cancers, Reg IV positivity in peritoneum-metastasis cases was higher than those in negative cases. Reg IV was detected in peritoneal lavage fluids from human gastric cancer patients, in whose lavages keratin mRNA was detected by reverse transcriptase-polymerase chain reaction. Collectively, Reg IV might accelerate peritoneal metastasis in gastric cancer. Reg IV in lavage fluids might be a good marker for peritoneal metastasis.