RESUMEN
CD44 standard isoform (CD44s) is a cancer stem cell marker in many tumors, and is one of the CD44 isoforms.CD44v6 has been reported to correlate with tumor progression and poor prognosis in colorectal cancer. However, the relevance of CD44s and CD44v6 to epithelial-mesenchymal transition (EMT) remains unclear. Immunohistochemistry was performed to investigate the clinical importance of CD44s and CD44v6 and their relevance to EMT in 113 patients with stage II/III colorectal cancer treated by curative resection. The relevance of CD44v6 knockdown to the phenotype of colon cancer cells was examined using small interfering RNA (siRNA) specific for CD44v6 in vitro. CD44v6 expression showed a significant inverse correlation with E-cadherin expression (P=0.0007) and a positive correlation with vimentin expression (P=0.0096). A multivariate analysis showed that high CD44v6 expression was an independent poor prognostic factor for disease-free survival (P=0.01, HR=3.05) and overall survival (P=0.025, HR=3.16). The clinical significance and the relevance of CD44s expression to EMT markers was noted to a lesser extent compared to CD44v6 expression. The knockdown of CD44v6 decreased vimentin expression, cell invasion and HGF-induced cell migration, but conferred only a slight effect on E-cadherin expression in colon cancer cells (HCT116 and LoVo). CD44v6 is related to poor outcome of patients with colorectal cancer via upregulation of the mesenchymal phenotype.
Asunto(s)
Neoplasias Colorrectales/genética , Transición Epitelial-Mesenquimal/genética , Receptores de Hialuranos/genética , Adulto , Anciano , Cadherinas/metabolismo , Movimiento Celular/genética , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células HCT116 , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/genética , Pronóstico , Vimentina/metabolismoRESUMEN
BACKGROUND: Exosomes are 40-nm to 100-nm membrane vesicles that are secreted by various cells, and they play a major role in cell-cell communication. The objective of this study was to clarify the significance of the levels of microRNA in exosomes extracted from the sera of patients with esophageal squamous cell cancer (ESCC). METHODS: The authors isolated exosomes in serum samples from patients who had ESCC and from patients who had benign diseases without systemic inflammation. Total RNA was purified from the exosomes, and expression levels of microRNA-21 (miR-21) were analyzed by quantitative real-time polymerase chain reaction. RESULTS: Serum exosomes from patients with ESCC induced the proliferation of ESCC cells in vitro. The expression levels of exosomal miR-21 were significantly higher in patients with ESCC than those with benign diseases with and without (C-reactive protein <0.3 mg/dL) systemic inflammation. MiR-21 was not detected in serum that remained after exosome extraction. Exosomal miR-21 expression was correlated with advanced tumor classification, positive lymph node status, and the presence of metastasis with inflammation or and clinical stage without inflammation (C-reactive protein <0.3 mg/dL). CONCLUSIONS: The current results confirmed that exosomal miR-21 expression is up-regulated in serum from patients with ESCC versus serum from patients who have benign diseases without systemic inflammation. Exosomal miR-21 was positively correlated with tumor progression and aggressiveness, suggesting that it may be a useful target for cancer therapy. Cancer 2013. © 2012 American Cancer Society.
Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Exosomas/genética , MicroARNs/sangre , Anciano , Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/inmunología , Línea Celular Tumoral , Progresión de la Enfermedad , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/inmunología , Carcinoma de Células Escamosas de Esófago , Exosomas/química , Femenino , Humanos , Inflamación/inmunología , Masculino , Persona de Mediana Edad , Regulación hacia ArribaRESUMEN
BACKGROUND: The microRNA-200 (miR-200) family has been reported to induce epithelial differentiation and suppress epithelial-mesenchymal transition (EMT) by inhibiting translation of zinc finger E-box-binding homeobox (ZEB) 1 and 2 mRNAs in several types of cancers. This study aimed to clarify the role of miR-200b in regulating EMT and promoting cellular proliferation, invasion, and migration in gastric cancer. METHODS: The relationships among the expression levels of miR-200b, ZEB1 and ZEB2, and E-cadherin mRNAs were analyzed by quantitative real-time reverse transcription-polymerase chain reaction in frozen tissue samples from 40 gastric cancer patients who underwent gastrectomy from 2008 to 2010. The effects of miR-200b on EMT in gastric cancer cells in vitro were also analyzed. RESULTS: Diffuse histologic type, depth of tumor, tumor size, lymph node metastasis, and lymphatic invasion were significantly higher in the low-miR-200b expression group compared with the high expression group. There was a strong correlation between the levels of miR-200b, and ZEB2 and E-cadherin mRNAs in gastric cancer patients. Upregulation of miR-200b in gastric cancer cells changed the cell morphology from fibroblast- to epithelial-like, associated with localization of E-cadherin to the plasma membrane. ZEB2 mRNA levels fell, while E-cadherin expression levels increased in gastric cells overexpressing miR-200b, associated with significantly reduced cellular proliferation, and inhibition of cellular migration and invasion. CONCLUSIONS: miR-200b regulates ZEB2 expression and thus controls metastasis in gastric cancer.
Asunto(s)
Carcinoma/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/metabolismo , MicroARNs/metabolismo , Proteínas Represoras/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Anciano , Anciano de 80 o más Años , Cadherinas/genética , Cadherinas/metabolismo , Carcinoma/secundario , Línea Celular Tumoral , Membrana Celular/metabolismo , Movimiento Celular , Proliferación Celular , Distribución de Chi-Cuadrado , Femenino , Proteínas de Homeodominio/genética , Humanos , Metástasis Linfática , Masculino , MicroARNs/genética , Invasividad Neoplásica , ARN Mensajero/metabolismo , Proteínas Represoras/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transfección , Carga Tumoral/genética , Regulación hacia Arriba , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc , Homeobox 1 de Unión a la E-Box con Dedos de ZincRESUMEN
BACKGROUND: It was recently revealed that microRNAs (miRNAs) can stably exist in serum and may affect the pathogenesis of several diseases. However, there are few reports that have demonstrated the significance of miRNAs in the serum of patients with esophageal squamous cell carcinoma (ESCC). Thus, the aims of this study were to clarify the status of miRNA-21 in serum of ESCC patients and to reveal the usefulness of this molecule as a biomarker. METHODS: We measured the miRNA-21 levels in serum samples from 71 ESCC patients and 39 healthy controls by using real-time RT-PCR. We also evaluated the changes in the miRNA-21 level during operation and chemotherapy. RESULTS: We found that serum concentration of miRNA-21 in ESCC patients was significantly higher than that in healthy controls (P < 0.001). A significant reduction in the serum miR-21 levels was observed in the postoperative samples versus the preoperative samples (P = 0.003). Furthermore, miRNA-21 levels were significantly reduced in ESCC patients who responded to chemotherapy (P = 0.003), whereas no significant change was observed in the non-responders. CONCLUSION: Serum miRNA-21 is considered to be a novel biomarker for diagnosing ESCC, and it can also be used as a response marker during chemotherapy for ESCC patients.
Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , MicroARNs/sangre , Adulto , Anciano , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Estudios de Casos y Controles , Quimioterapia Adyuvante , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Esofagectomía , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Tiempo , Resultado del TratamientoRESUMEN
A binaphthyl-based primary amine (R)- was designed for the Diels-Alder reaction of alpha-substituted alpha,beta-unsaturated aldehydes; in the presence of the TfOH salt of (R)-, the Diels-Alder reaction of alpha-substituted alpha,beta-unsaturated aldehydes with cyclopentadiene proceeded to afford the corresponding cycloadducts having one all-carbon quaternary stereocenter in good yield with good to high stereoselectivity.
Asunto(s)
Aldehídos/química , Aminas/química , Mesilatos/química , Acroleína/síntesis química , Acroleína/química , Aldehídos/síntesis química , Aminas/síntesis química , Catálisis , Ciclopentanos/síntesis química , Ciclopentanos/química , Mesilatos/síntesis química , EstereoisomerismoRESUMEN
A new synthetic route to 3,3'-dihalo BINAMs based on the direct halogenation of H8-BINAM and subsequent rearomatization to the binaphthyl core has been developed. The combination of this new procedure and Pd-catalyzed coupling reactions enabled us to synthesize various 3,3'-disubstituted BINAMs in only three steps starting from H8-BINAM.
Asunto(s)
Diaminas/síntesis química , Naftalenos/síntesis química , Diaminas/química , Conformación Molecular , Naftalenos/química , EstereoisomerismoRESUMEN
A series of symmetrical chiral phase-transfer catalysts with 4,4',6,6'-tetrasubstituted binaphthyl units have been designed, and these aryl- and trialkylsilyl-substituted phase-transfer catalysts, which included a highly fluorinated catalyst, were prepared. The chiral efficiency of these chiral phase-transfer catalysts was investigated in the asymmetric alkylation of tert-butylglycinate-benzophenone Schiff base under mild phase-transfer conditions, and the eminent substituent effect of the 4,4',6,6'-positions of the binaphthyl units on enantioselection was observed. In particular, the OctMe2Si-substituted catalyst was found to be highly efficient for the phase-transfer alkylation of tert-butylglycinate-benzophenone Schiff base with various alkyl halides, including sec-alkyl halides. The highly fluorinated catalyst was also utilized as a recyclable chiral phase-transfer catalyst by simple extraction with fluorous solvents.
RESUMEN
An organocatalyst formed from a binaphthyl-substituted diamine and trifluoromethanesulfonic acid exhibited unprecedented levels of exo selectivity in the Diels-Alder reaction of alpha,beta-unsaturated aldehydes with cyclopentadiene. A novel axially chiral diamine was also designed as an organocatalyst for an asymmetric variant of this reaction, in which the desired cycloadducts were formed with high diastereo- and enantioselectivities. The highest diastereoselectivity observed was greater than 20:1 in favor of the exo cycloadduct in the asymmetric Diels-Alder reaction of crotonaldehyde with cyclopentadiene.
RESUMEN
[reaction: see text] A novel binaphthyl-based diamine (R)-2 was designed and synthesized. A protonic acid-(R)-2 salt catalyst has the advantage of exhibiting unprecedented high exo selectivity in the asymmetric Diels-Alder reaction of alpha,beta-unsaturated aldehydes. For instance, the reaction between cinnamaldehyde and cyclopentadiene in the presence of 12 mol % of binaphthyl-based diamine (R)-2 and 10 mol % of p-TsOH.H(2)O in alpha,alpha,alpha-trifluorotoluene at -20 degrees C gave the corresponding exo cycloadduct with 92% ee as a major diastereomer (exo/endo = 13/1).
RESUMEN
The treatment of complicated syndactyly has been a difficult problem because it involves not only cutaneous syndactyly but also abnormal arrangement of the finger rays. This means that this anomaly is characterized by abnormal patterns of the palmar creases. The authors prepared a template for tracing the proximal, middle, and distal palmar creases of the nonaffected hand on a clear film and used it as a mirror image to create the preoperative design, to measure the distance between the fingers, and to estimate the location and size of the skin graft intraoperatively. The authors think that the recreation of the normal palmar crease pattern in the affected hand can lead to normal arrangement of the fingers and it is very useful for the reconstruction of multiple finger webbing as part of the treatment of complicated syndactyly.
Asunto(s)
Trasplante de Piel , Sindactilia/cirugía , Femenino , Humanos , Lactante , Masculino , Procedimientos de Cirugía PlásticaRESUMEN
[structure: see text] A recyclable fluorous chiral phase-transfer catalyst was synthesized and successfully applied for the catalytic asymmetric synthesis of both natural and unnatural alpha-amino acids. The reaction involves alkylation of a glycine derivative followed by extractive recovery of the chiral phase-transfer catalyst using fluorous solvent.