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1.
World J Oncol ; 13(5): 289-298, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36406192

RESUMEN

Background: As one of the most widely used anti-diabetic drugs for type II diabetes, metformin has been shown to exhibit anti-cancer activity in recent years. Epidermal growth factor (EGF) and its receptor, EGFR, play important roles in cancer metastasis in various tumors, including breast cancer. Epithelial-mesenchymal transition (EMT) is a critical process for cancer invasion and metastasis. In this study, we use EGF as a metastatic inducer to investigate the effect of metformin on cancer cell migration, invasion and EMT. Methods: Human breast cancer MCF-7 cells were exposed to EGF with or without metformin or N-acetyl cysteine (NAC). The effects of metformin on breast cancer cell proliferation were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The production of reactive oxygen species (ROS) was tested using 2,7-dichlorodihydrofluorecein diacetate (DCFH-DA). The migratory and invasive abilities of tumor cells were analyzed using wound healing assay and transwell invasion assay, respectively. The expressions of E-cadherin, N-cadherin and Snail were tested using real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting at mRNA and protein levels. The activation of protein kinase B (Akt) and nuclear factor kappa B (NF-κB) were measured by western blotting. Results: Our results showed that metformin inhibited breast cancer cell proliferation in a dose-dependent manner with or without EGF. EGF-induced alterations in cell morphology that are characteristic of EMT were reversed by metformin. Metformin also inhibited the EGF-modulated expression of E-cadherin, N-cadherin and Snail and further suppressed cell invasion and migration. In addition, metformin suppressed EGF-induced phosphorylation of Akt and NF-κB. ROS is involved in EGF-induced cancer invasion and activation of phosphatidylinositol 3-kinase (PI3K)/Akt/NF-κB pathway. Conclusion: Taken together, these data indicate that metformin suppresses EGF-induced breast cancer cell migration, invasion and EMT through the inhibition of the PI3K/Akt/NF-κB pathway. These results provide a novel mechanism to explain the role of metformin as a potent anti-metastatic agent in breast cancer cells.

2.
Tumour Biol ; 37(7): 8715-20, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26738867

RESUMEN

This study examined the association between hector battifora mesothelial antigen-1 (HBME-1) expression and papillary thyroid carcinoma (PTC). A total of 206 patients were enrolled in the current study including 96 PTC patients and 110 patients with benign thyroid nodules (BTN). Immunohistochemistry (Envision) were performed to assess the expression of HBME-1. Receiver operating characteristic curve (ROC) curves were applied to evaluate the diagnostic tumor node metastasis (TNM) value of HBME-1. Specimens from 96 patients with PTC and 110 patients with BTC were reviewed. HBME-1 was positively immunostained in PTC tissue, which was significantly higher than that in BTN tissues (77.1 vs. 5.77 %, P < 0.05). Immunohistochemistry also identified that HBME-1 expression did not show any statistically significant differences based on gender, age, tumor size, TNM stage, and lymph node metastasis (P > 0.05). Importantly, HBME-1 expression was correlated with infiltration levels and differential levels in PTC (both P < 0.05). HBME-1 was found to have high sensitivity (94.5 %) and specificity (77.08 %) for PTC diagnosis. Moreover, HBME-1 had a high specificity (83.33 %) at identifying the differential levels of PTC, but a low sensitivity (22.92 %). The sensitivity and specificity of HBME-1 identifying the infiltration levels of PTC were, respectively, 72.70 and 72.00 %. HBME-1 was highly expressed in PTC tissues, and HBME-1 can serve as a potential biomarker in the diagnosis of PTC.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma/diagnóstico , Carcinoma/metabolismo , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/metabolismo , Adolescente , Adulto , Carcinoma/patología , Carcinoma Papilar , Femenino , Humanos , Inmunohistoquímica/métodos , Metástasis Linfática/diagnóstico , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Curva ROC , Sensibilidad y Especificidad , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/metabolismo , Nódulo Tiroideo/patología , Adulto Joven
3.
Dig Surg ; 31(4-5): 297-305, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25376486

RESUMEN

BACKGROUND/AIMS: The accurate staging of pancreatic cancer (PanCa) is crucial in the development of a stage-specific treatment plan for PanCa patients. We aimed to perform a meta-analysis of endoscopic ultrasonography (EUS) in the tumor node (TN) staging and evaluation of vascular invasion in PanCa. METHODS: A meta-analysis of diagnostic accuracy parameters was performed to evaluate the EUS-based TN staging, and vascular invasion by PanCa was compared to the results of intraoperative staging or to the histopathology of resected specimens. RESULTS: Twenty studies with 726 PanCa cases were identified from 281 articles. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 0.72, 0.90, 6.27, 0.28, and 24.69, respectively, for T1-2 staging and 0.90, 0.72, 3.58, 0.16, and 24.69, respectively, for T3-4 staging. The overall sensitivity, specificity, PLR, NLR, and DOR were 0.62, 0.74, 2.54, 0.51, and 6.67, respectively, for N staging (positive vs. negative) and 0.87, 0.92, 7.16, 0.20, and 56.19, respectively, for vascular invasion. The area under the curve was 0.90, 0.90, 0.79, and 0.94 for T1-2 staging, T3-4 staging, N staging, and vascular invasion, respectively. CONCLUSIONS: EUS is a reliable and accurate diagnostic tool for the TN staging and evaluation of vascular invasion in PanCa. The nodal staging accuracy using EUS is less satisfactory.


Asunto(s)
Endosonografía/métodos , Ganglios Linfáticos/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Neoplasias Vasculares/secundario , Femenino , Humanos , Masculino , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Sensibilidad y Especificidad , Neoplasias Vasculares/diagnóstico por imagen
4.
World J Surg Oncol ; 12: 220, 2014 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-25029913

RESUMEN

Necrolytic migratory erythma (NME) is an obligatory paraneoplastic syndrome. Here we describe a woman admitted to the dermatology ward with NME which was later found to be associated with glucagonoma, a slow-growing, rare pancreatic neuroendocrine tumor. Even more rarely, the tumor was located in the pancreas head, while most of such lesions are located in the distal pancreas. The diagnosis of this rare tumor requires an elevated serum glucagon level and imaging confirming a pancreatic tumor. After surgical removal of the tumor, the patient's cutaneous and systemic features resolved. It is therefore imperative that clinicians recognize NME early in order to make an accurate diagnosis and to provide treatment for this rare tumor.


Asunto(s)
Glucagonoma/diagnóstico , Eritema Necrolítico Migratorio/diagnóstico , Tumores Neuroendocrinos/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adulto , Femenino , Glucagón/metabolismo , Glucagonoma/complicaciones , Glucagonoma/cirugía , Humanos , Eritema Necrolítico Migratorio/complicaciones , Eritema Necrolítico Migratorio/cirugía , Tumores Neuroendocrinos/complicaciones , Tumores Neuroendocrinos/cirugía , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/cirugía , Pronóstico
5.
Asian Pac J Cancer Prev ; 14(7): 4161-5, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23991970

RESUMEN

OBJECTIVE: To investigate discriminating protein patterns and potential biomarkers in serum samples between pre/postoperative pancreatic cancer patients and healthy controls. METHODS: 23 serum samples from PC patients (12 preoperative and 11 postoperative) and 76 from healthy controls were analyzed using matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) technique combined with magnetic beads-based weak cation-exchange chromatography (MB-WCX). ClinProTools software selected several markers that made a distinction between pancreatic cancer patients and healthy controls. RESULTS: 49 m/z distinctive peaks were found among the three groups, of which 33 significant peaks with a P < 0.001 were detected. Two proteins could distinguish the preoperative pancreatic cancer patients from the healthy controls. About 15 proteins may be potential biomarkers in assessment of pancreatic cancer resection. CONCLUSION: MB-MALDI-TOF-MS method could generate serum peptidome profiles of pancreatic cancer and provide a new approach to identify potential biomarkers for diagnosis and prognosis of this malignancy.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma Ductal Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adulto , Anciano , Carcinoma Ductal Pancreático/sangre , Carcinoma Ductal Pancreático/cirugía , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/cirugía , Periodo Posoperatorio , Periodo Preoperatorio , Pronóstico , Proteómica , Programas Informáticos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
6.
PLoS One ; 6(6): e19881, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21698226

RESUMEN

BACKGROUND: Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingør, Denmark. METHODOLOGY: Literature search in databases as PUBMED and ISI Web of Science in combination with manual search was used to answer the following five questions: (1)Can resveratrol be recommended in the prevention or treatment of human diseases?; (2)Are there observed "side effects" caused by the intake of resveratrol in humans?; (3)What is the relevant dose of resveratrol?; (4)What valid data are available regarding an effect in various species of experimental animals?; (5)Which relevant (overall) mechanisms of action of resveratrol have been documented? CONCLUSIONS/SIGNIFICANCE: The overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources. On the other hand, animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials. Finally, we suggest directions for future research in resveratrol regarding its mechanism of action and its safety and toxicology in human subjects.


Asunto(s)
Estilbenos/farmacología , Humanos , Resveratrol , Estilbenos/administración & dosificación , Estilbenos/efectos adversos
7.
World J Gastroenterol ; 17(21): 2667-73, 2011 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-21677838

RESUMEN

AIM: To investigate the silencing effects of pAd-shRNA-pleiotrophin (PTN) on PTN in pancreatic cancer cells, and to observe the inhibition of pAd-shRNA-PTN on neurite outgrowth from dorsal root ganglion (DRG) neurons in vitro. METHODS: PAd-shRNA-PTN was used to infect pancreatic cancer BxPC-3 cells; assays were conducted for knockdown of the PTN gene on the 0th, 1st, 3rd, 5th, 7th and 9th d after infection using immunocytochemistry, real-time quantitative polymerase chain reaction (PCR), and Western blotting analysis. The morphologic changes of cultured DRG neurons were observed by mono-culture of DRG neurons and co-culture with BXPC-3 cells in vitro. RESULTS: The real-time quantitative PCR showed that the inhibition rates of PTN mRNA expression in the BxPC-3 cells were 20%, 80%, 50% and 25% on the 1st, 3rd, 5th and 7th d after infection. Immunocytochemistry and Western blotting analysis also revealed the same tendency. In contrast to the control, the DRG neurons co-cultured with the infected BxPC-3 cells shrunk; the number and length of neurites were significantly decreased. CONCLUSION: Efficient and specific knockdown of PTN in pancreatic cancer cells and the reduction in PTN expression resulted in the inhibition of neurite outgrowth from DRG neurons.


Asunto(s)
Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Citocinas/genética , Citocinas/metabolismo , Ganglios Espinales/citología , Neuritas/fisiología , Neuronas/metabolismo , Neoplasias Pancreáticas/metabolismo , ARN Interferente Pequeño/metabolismo , Adenoviridae/genética , Adenoviridae/metabolismo , Células Cultivadas , Técnicas de Cocultivo , Neuronas/citología , Neoplasias Pancreáticas/genética , ARN Interferente Pequeño/genética
8.
Biol Pharm Bull ; 33(8): 1261-7, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20686216

RESUMEN

Pancreatic cancer is the fourth leading cause of cancer-related death in the western countries and it is resistant to almost all cytotoxic drugs. In the current study, we explored the gemcitabine resistance induced by the interaction between Annexin A2 (ANXA2) and alternatively spliced segment of tenascin-C (TNfnA-D). In the pancreatic cancer cell culture system in vitro, it was proved that exogenous recombinant TNfnA-D combined with the cell surface ANXA2 specifically and their interaction suppressed gemcitabine-induced cytotoxicity on pancreatic cancer cells in a dose-dependent manner. Meanwhile, the TNfnA-D/ANXA2 interaction increased the phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, inhibitory kappaB (IkappaB) kinase alpha/beta (IKKalpha/beta), IkappaBalpha, and p65 nuclear factor-kappaB (NF-kappaB) significantly. Inhibition of Akt and PI3K with their specific inhibitors partially reversed the suppression of gemcitabine-induced cytotoxicity elicited by TNfnA-D/ANXA2 interaction. Activation of p65 NF-kappaB was dependent on the phosphorylation of PI3K/Akt. The phosphorylated IKKalpha/beta induced the phosphorylation and degradation of IkappaBalpha, the sequential phosphorylation, nuclear translocation and activation of p65 NF-kappaB. Pyrrolidine dithiocarbamate (PDTC) effectively blocked the activity of p65 NF-kappaB in response to TNfnA-D. Down-regulation of p65 NF-kappaB with its specific small interfering RNA (siRNA) restored the gemcitabine-induced cytotoxicity suppressed by TNfnA-D/ANXA2 interaction. For the first time, this study show that ANXA2/TNfnA-D interaction induced gemcitabine resistance via the canonical PI3K/Akt/NF-kappaB signaling pathways in pancreatic cancer cells. Therefore, therapy targeting ANXA2/TNfnA-D and/or p65 NF-kappaB may have potential clinical application for patients with pancreatic cancers.


Asunto(s)
Empalme Alternativo , Anexina A2/biosíntesis , Antimetabolitos Antineoplásicos/farmacología , Desoxicitidina/análogos & derivados , Resistencia a Antineoplásicos , Neoplasias Pancreáticas/patología , Tenascina/biosíntesis , Anexina A2/genética , Western Blotting , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Desoxicitidina/farmacología , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Resistencia a Antineoplásicos/genética , Citometría de Flujo , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Fosforilación , Regiones Promotoras Genéticas , Unión Proteica , ARN Interferente Pequeño/genética , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Tenascina/genética , Factor de Transcripción ReIA/biosíntesis , Gemcitabina
9.
Cancer Biol Ther ; 10(1): 19-29, 2010 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-20424515

RESUMEN

Smoking and chronic stress are well-documented risk factors that are associated with ß-adrenoceptors in the development of pancreatic cancer. Stimulation of ß-adrenoceptors can activate cyclic adenosine monophosphate (cAMP)/ protein kinase A (PKA) and mitogen-activated protein kinase (MAPK) pathways in pancreatic cancer cells. Many recent studies have focused on the function of ß-adrenoceptors in cancer invasion. Thus, we hypothesized that ß-adrenoceptors may play a role in pancreatic cancer invasion, and ß-blockers may suppress the pancreatic cancer invasion and proliferation. MIA PaCa-2 and BxPC-3 cell lines express mRNA and protein of both ß1 and ß2-adrenoceptors. ß2-adrenergic antagonist ICI118,551 and ß1/2-adrenergic antagonist propranolol significantly suppressed cell invasion and proliferation in comparison to ß1-adrenergic antagonist metoprolol and control in a Matrigel invasion assay and subrenal capsular assay. Treatment with ß2-adrenoceptor antagonists inhibited activation of transcription factors nuclear factor κB (NF-κB), activator protein 1 (AP-1) and cAMP response element binding protein (CREB) as demonstrated by electrophoretic mobility shift assays and Western blotting. ß2-adrenoceptor antagonists also significantly altered vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), matrix metalloproteinase 2 (MMP-2) and MMP-9 expression. The ß2-adrenergic antagonists suppressed invasion and proliferation by inhibiting both cAMP/PKA and Ras, which regulate activation of the MAPK pathway and transcription factors, such as NF-κB, AP-1 and CREB, as well as expression of its target genes, MMP-9, MMP-2 and VEGF. However, ß1-adrenergic antagonists suppressed invasion by inhibiting only the cAMP/PKA pathway, suggesting that they may be useful as novel preventive and therapeutic strategies for pancreatic cancer.


Asunto(s)
Antagonistas de Receptores Adrenérgicos beta 2/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/antagonistas & inhibidores , FN-kappa B/antagonistas & inhibidores , Neoplasias Pancreáticas/tratamiento farmacológico , Propanolaminas/farmacología , Factor de Transcripción AP-1/antagonistas & inhibidores , Animales , Western Blotting , Línea Celular Tumoral , Proliferación Celular , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Ensayo de Cambio de Movilidad Electroforética , Ensayo de Inmunoadsorción Enzimática , Humanos , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , FN-kappa B/metabolismo , Invasividad Neoplásica , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , ARN Mensajero/genética , Receptores Adrenérgicos beta/genética , Receptores Adrenérgicos beta/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción AP-1/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo
10.
Nan Fang Yi Ke Da Xue Xue Bao ; 30(1): 70-5, 2010 Jan.
Artículo en Chino | MEDLINE | ID: mdl-20117988

RESUMEN

OBJECTIVE: To study the effects of L-arginine (L-Arg) on human colon carcinoma cell line LS174 through NO pathway and the mechanism. METHODS: LS174 cells were cultured in the presence of L-Arg at different concentrations for different time. MTT assay was employed to evaluate the cell proliferation, and the cell morphological changes were observed by optical and electron microscopy. The apoptosis of L-Arg-treated cells was observed by the Annexin V/PI staining. The expression levels of VEGF, COX-2, p53, bcl-2 and bax in the cells were determined using Western blotting and immunocytochemical staining. RESULTS: L-Arg promoted the growth of LS174 cells at a low concentration (0.125 mmol/L) and inhibited the cell growth at higher concentrations (0.5, 2, 8, and 32 mmol/L). Under electron microscope, ultrastructual changes in the cytoplasm and nuclei of LS174 cells were observed 48 h after exposure to L-Arg. Some of the cells showed morphological changes characteristic of cell apoptosis such as cell size reduction, condensation and margination of the nuclear chromatin. Low concentration of L-Arg resulted in a cell apoptosis rate of 2.29%, as compared with the rate of 2.84% in the control group; at higher concentrations, L-Arg caused significantly increased cell apoptosis rates to 26.88%, 28.95%, 63.36%, and 84.51%, respectively. In cells treated with a low concentration of L-Arg, the expressions of VEGF and COX-2 were increased as compared with those in the control cells; higher concentrations of L-Arg obviously decreased the expressions of p53 and bcl-2 and increased the expression of bax. CONCLUSION: Low-concentration L-Arg can promote the growth of LS174 cells probably by up-regulating VEGF and COX-2 protein under the influence of NO, the metabolite of L-Arg. The inhibitory effect of high concentrations of L-Arg is probably mediated by inducing cell apoptosis via NO. The mechanism of L-Arg- induced cell apoptosis may be related to the up-regulation of bax protein and the down-regulation of p53 and bcl-2 proteins.


Asunto(s)
Apoptosis/efectos de los fármacos , Arginina/farmacología , Neoplasias del Colon/patología , Óxido Nítrico/metabolismo , Línea Celular Tumoral , Ciclooxigenasa 2/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Factor A de Crecimiento Endotelial Vascular/metabolismo
11.
Acta Pharmacol Sin ; 31(1): 102-10, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20037603

RESUMEN

AIM: To examine whether beta-adrenoceptor (beta-AR) agonists can induce hypoxia-inducible factor (HIF)-1alpha accumulation which then up-regulate the expression of its target genes in pancreatic cancer cells at normoxia, and to further elucidate the mechanism involved. METHODS: Pulse-chase assay, RT-PCR, and Western blot were employed to detect the effects of beta-AR agonists and antagonists, siRNA as well as several inhibitors of signal transduction pathways on MIA PaCa2 and BxPC-3 pancreatic cancer cells. RESULTS: Treatment of pancreatic cancer cell lines with beta-AR agonists led to accumulation of HIF-1alpha and then up-regulated expression of its target genes independently of oxygen levels. The induction was partly or completely inhibited not only by beta-AR antagonists but also by inhibitors of PKA transduction pathways and by siHIF-1alpha. Both beta1-AR and beta2-AR agonists produced the above-mentioned effects, but beta2-AR agonist was more potent. CONCLUSION: Activation of beta-AR receptor transactivates epidermal growth factor receptor (EGFR) and then elicits Akt and ERK1/2 in a PKA-dependent manner, which together up-regulate levels of HIF-1alpha and downstream target genes independently of oxygen level. Our data suggest a novel mechanism in pancreatic cancer cells that links beta-AR and HIF-1alpha signaling under normoxic conditions, with implications for the control of glucose transport, angiogenesis and metastasis.


Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Subunidad alfa del Factor 1 Inducible por Hipoxia/efectos de los fármacos , Neoplasias Pancreáticas/metabolismo , Agonistas de Receptores Adrenérgicos beta 1 , Agonistas de Receptores Adrenérgicos beta 2 , Western Blotting , Línea Celular Tumoral , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Receptores ErbB/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Interferente Pequeño/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos
12.
Nan Fang Yi Ke Da Xue Xue Bao ; 29(10): 2084-7, 2009 Oct.
Artículo en Chino | MEDLINE | ID: mdl-19861273

RESUMEN

OBJECTIVE: To evaluate the effect of transcatheter arterial chemoembolization (TACE) with high-dose iodized oil on hepatic tumor growth and metastasis in rabbits. METHODS: Forty-eight rabbits with implanted VX2 tumor were randomly divided into control group, routine dose iodized oil TACE group and high-dose iodized oil TACE group to receive perfusion through the hepatic artery with 0.9% saline, 5 mg adriamycin with routine-dose iodized oil, and 5 mg adriamycin with high-dose iodized oil, respectively. The tumor volume, tumor necrosis, intrahepatic and lung metastasis were examined 2 weeks after TACE. RESULTS: No significant difference was found in the tumor volume between the 3 groups before TACE (P>0.05). The rabbits receiving TACE with iodized oil, especially at the high dose, showed significantly reduced tumor volume as compared with the control group (P<0.01). TACE with high-dose iodized oil resulted in significantly increased tumor necrosis rate in comparison with the control group and TACE with a routine dose of iodized oil (P<0.05); high-dose iodized oil TACE was also associated with reduced intrahepatic and lung metastasis as compared routine dose iodized oil TACE (P<0.05). CONCLUSION: TACE with high-dose iodized oil can obviously inhibit the growth and intrahepatic and lung metastasis of transplanted VX2 liver tumor in rabbits .


Asunto(s)
Quimioembolización Terapéutica , Medios de Contraste/administración & dosificación , Aceite Yodado/administración & dosificación , Neoplasias Hepáticas Experimentales/terapia , Animales , Cateterismo Periférico , Quimioembolización Terapéutica/métodos , Relación Dosis-Respuesta a Droga , Portadores de Fármacos/administración & dosificación , Femenino , Arteria Hepática , Masculino , Conejos
13.
Nan Fang Yi Ke Da Xue Xue Bao ; 29(6): 1141-3, 2009 Jun.
Artículo en Chino | MEDLINE | ID: mdl-19726343

RESUMEN

OBJECTIVE: To investigate the expression of survivin in acute pancreatitis in rats. METHODS: Acute pancreatitis was induced in rats by retrograde injection of sodium taurocholate into the pancreaticobiliary duct. The expressions of survivin in the pancreatic tissues was detected by immunohistochemisty, Western blotting and RT-PCR, and the apoptotic ratio of the acinar cells was determined by TUNEL assay. RESULTS: Survivin was not detected in the control group, and in rat models of acute pancreatitis, the expressions of survivin protein and mRNA increased but the apoptotic index of the acinar cells decreased gradually with the severity of inflammation. CONCLUSION: Survivin is involved in the regulation of acinar cell apoptosis and also the necrosis of the apoptotic acinar cells through its anti-apoptosis activity to aggravate acute pancreatitis, suggesting its value as a promising marker in predicting the severity of acute pancreatitis.


Asunto(s)
Apoptosis/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Pancreatitis/genética , Pancreatitis/patología , Enfermedad Aguda , Animales , Biomarcadores , Masculino , Proteínas Asociadas a Microtúbulos/genética , Pancreatitis/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Survivin , Ácido Taurocólico
14.
World J Gastroenterol ; 15(20): 2543-6, 2009 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-19469007

RESUMEN

AIM: To assess the role of magnetic resonance cholangiopancreatography (MRCP) in detection of pancreatic duct stones (PDS) in patients with chronic pancreatitis (CP). METHODS: Clinical data of 78 CP patients who were treated at the First Affiliated Hospital of Xi'an Jiaotong University (China) between January 2004 and July 2008 were retrospectively analyzed. A predictive model of pancreatic duct stones was established through logistic regression and its effectiveness was verified. Among these patients, MRCP was performed in 60 patients who served as a control group, while 44 patients with a higher predictive value than the entry threshold of the predictive model served as an experimental group. RESULTS: The positive rate of PDS in the 78 patients with CP was 19.2% (15/78). The predictive entry threshold of the predictive model was 5% (P < 0.05). The possibility of existence of PDS could be predicted according to the following 4 indexes: gastrointestinal symptoms, intermittent abdominal pain, diabetes mellitus (DM)/impaired glucose tolerance (IGT) and positive B-mode ultrasound results. The incidence of PDS in the experimental group was higher than that in the control group (P < 0.05). CONCLUSION: MRCP is strongly suggested for the detection of PDS in patients with gastrointestinal symptoms, intermittent abdominal pain, DM/IGT and positive B-mode ultrasound results.


Asunto(s)
Cálculos/diagnóstico , Pancreatocolangiografía por Resonancia Magnética/estadística & datos numéricos , Conductos Pancreáticos/patología , Pancreatitis Crónica/diagnóstico , Adolescente , Adulto , Anciano , Cálculos/patología , Pancreatocolangiografía por Resonancia Magnética/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/patología , Pancreatitis Crónica/fisiopatología , Adulto Joven
15.
Nan Fang Yi Ke Da Xue Xue Bao ; 29(3): 454-7, 2009 Mar.
Artículo en Chino | MEDLINE | ID: mdl-19304523

RESUMEN

OBJECTIVE: To investigate the effect of resveratrol on the apoptosis of pancreatic acinar cells in rats with severe acute pancreatitis (SAP) and explore the mechanism of such effect. METHOD: SD rats with 3.5% sodium taurocholate-induced SAP were treated with resveratrol, and the serum amylase was detected with automatic biochemistry analyzer. The apoptosis of the pancreatic acinar cells in the rats was detected by TUNEL assay, and the expression of Fas and FasL genes was determined by RT-PCR and Western blotting. The pathological changes of the pancreas were observed under optical microscope. RESULTS: Compared with SAP group, the resveratrol-treated rats showed obviously decreased serum amylase and scores for pancreatic histopathological lesions. Resveratrol treatment significantly increased the apoptotic indices of pancreatic acinar cells and the levels of FasL mRNA and protein in rats with SAP. CONCLUSION: Resveratrol produces important therapeutic effect on SAP in rats by inducing pancreatic acinar cell apoptosis possibly as a result of up-regulated FasL gene expression.


Asunto(s)
Apoptosis/efectos de los fármacos , Proteína Ligando Fas/metabolismo , Páncreas Exocrino/patología , Pancreatitis Aguda Necrotizante/tratamiento farmacológico , Estilbenos/uso terapéutico , Animales , Proteína Ligando Fas/efectos de los fármacos , Proteína Ligando Fas/genética , Masculino , Pancreatitis Aguda Necrotizante/inducido químicamente , Pancreatitis Aguda Necrotizante/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Resveratrol , Ácido Taurocólico , Regulación hacia Arriba
16.
Cancer Lett ; 283(2): 119-24, 2009 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-19232458

RESUMEN

Recent studies have demonstrated that pancreatic adenocarcinoma cells require hedgehog (HH) signaling for proliferation and survival. Mutations in the smoothened (SMOH) gene and loss-of-function mutations in the patched (PTCH) gene, which are involved in the HH signaling pathway, may cause pancreatic tumors. Since HH signaling pathway may contribute to the induction and maintenance of pancreatic tumors, the use of HH pathway inhibitors for targeting the pancreatic cancer might represent a novel therapeutic approach to advanced pancreatic carcinoma. Among the HH inhibitors, cyclopamine inhibits HH signaling through direct interaction with SMOH and retards the growth of cancer cells by inhibiting stem cells. Novel therapies that target the HH signaling pathway should become one of the more effective treatments for pancreatic cancer, which cannot be cured with current therapies.


Asunto(s)
Antineoplásicos/farmacología , Proteínas Hedgehog/antagonistas & inhibidores , Neoplasias Pancreáticas/tratamiento farmacológico , Transducción de Señal/fisiología , Alcaloides de Veratrum/farmacología , Animales , Proteínas Hedgehog/efectos de los fármacos , Humanos , Neoplasias Pancreáticas/genética
17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 39(5): 740-3, 2008 Sep.
Artículo en Chino | MEDLINE | ID: mdl-19024303

RESUMEN

OBJECTIVE: To test the effect of resvertrol on protecting the intestinal mucosal barrier in rats with severe acute pancreatitis. METHODS: Twenty four SD rats were randomly divided into three groups: severe acute pancreatitis without treatments (SAP group), severe acute pancreatitis with sham-operations (SO group), and severe acute pancreatitis treated with resveratrol (RES group). Specimen were obtained 6 hours after the severe acute pancreatitis was induced. The endotoxin level in the blood taken from portal vein was measured with turbidimetry. Apoptosis of mucosal cells was detected by TUNEL methods. The expressions of Bax and Bcl-2 mRNA in intestinal mucosal cells were determined by semi-quantitative RT-PCR. Mitochondrial membranous electric potential of intestinal mucosal cells was measured by confocal microscopy. RESULTS: The RES group had less serum endotoxin in portal vein than the SAP group (P < 0.01). The SAP group had higher apoptotic index of mucosal cells than the RES group (P < 0.01). The SAP group had higher expression of Bax mRNA in intestinal mucosal cells and lower expression of Bcl-2 mRNA than the RES group (P < 0.01). The SAP group had lower mitochondrial membranous electric potential of intestinal mucosal cells than the REA group (P < 0.01). CONCLUSION: Resvertrol inhibits the apoptosis of intestinal mucosa cells and protects the intestinal barrier function, which might prevent the translocation of bacteria and endotoxin in patients with severe acute pancreatitis.


Asunto(s)
Traslocación Bacteriana/efectos de los fármacos , Mucosa Intestinal/fisiopatología , Pancreatitis Aguda Necrotizante/fisiopatología , Estilbenos/farmacología , Animales , Apoptosis/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Pancreatitis Aguda Necrotizante/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Resveratrol
18.
Cell Biol Int ; 32(12): 1530-5, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18801449

RESUMEN

Stimulation of mice dorsal root ganglion neurons (DRGNs) activity by human pancreatic cancer (PanCa) cell line Mia PaCa-2 and its potential molecule mechanism has been investaged. DRGNs were cultured alone or along with the MIA PaCa-2. The effects of MIA PaCa-2 to DRGNs were determined by neurofilament (NF) immunocytochemical and Nissl staining. ELISA was used to detect the concentration of insulin-like growth factor-1 (IGF-1) in the culture supernatant. Cyton size, neurite outgrowth and neuronal activity in the experimental group were greater than in the control groups. However, the concentration of IGF-1 in the supernatants was not significantly different from those in the blank and non-cultured medium groups. In the presence of MIA PaCa-2 cell line, cyton size, neurite outgrowth and neuronal activity were enhanced, which may provide more routes for the invasion of cancer cells along nerves.


Asunto(s)
Comunicación Celular/fisiología , Ganglios Espinales/metabolismo , Conos de Crecimiento/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Invasividad Neoplásica/fisiopatología , Células Receptoras Sensoriales/metabolismo , Animales , Animales Recién Nacidos , Carcinoma/metabolismo , Carcinoma/fisiopatología , Aumento de la Célula/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Medios de Cultivo Condicionados/farmacología , Ganglios Espinales/citología , Ganglios Espinales/efectos de los fármacos , Conos de Crecimiento/efectos de los fármacos , Conos de Crecimiento/ultraestructura , Humanos , Ratones , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/fisiopatología , Nervios Periféricos/metabolismo , Nervios Periféricos/patología , Nervios Periféricos/fisiopatología , Células Receptoras Sensoriales/citología , Células Receptoras Sensoriales/efectos de los fármacos
19.
Nan Fang Yi Ke Da Xue Xue Bao ; 28(9): 1542-5, 2008 Aug.
Artículo en Chino | MEDLINE | ID: mdl-18819863

RESUMEN

OBJECTIVE: To investigate the protective effect of resvertrol on the intestinal mucosal cells in rats with severe acute pancreatitis and explore the possible mechanism. METHODS: Twenty-four SD rats were randomly divided into the sham-operation (SO) group, severe acute pancreatitis (SAP) group and resveratrol-treated (RES) group. In the SO group, the pancreases were slightly flipped only. In the SAP and RES groups, SAP model was established by retrograde injection of 40 g/L sodium chrolate (1 ml/kg) through the pancreatic duct, and in the latter group, resveratrol (10 mg/kg) was given intravenously. Specimens were obtained 6 h after SAP model establishment and the endotoxin levels in the portal vein was determined with turbidimetry to evaluate the effect of resversatrol on the intestinal endotoxin translocation in SAP rats. Apoptosis of the mucosal cells was detected by TUNEL methods, and the expression of bax and bcl-2 mRNA were determined by RT-PCR. The mitochondrial membrane potential of the intestinal mucosal cells was measured by confocal microscopy. RESULTS: The endotoxin levels in the portal vein were significantly lower in RES group than in SAP group (P<0.01). TUNEL assay demonstrated significantly higher apoptotic index of the mucosal cells in SAP group than that in RES group (P<0.01). The expression of Bax mRNA in the intestinal mucosal cell was significantly higher in SAP group than in RES group (P<0.01), whereas the expression of bcl-2 mRNA was significantly lower in SAP group (P<0.01). The mitochondrial membrane potential of the intestinal mucosal cell was significantly lower in SAP group than in RES group (P<0.01). CONCLUSION: Resvertrol can inhibit the apoptosis of the intestinal mucosa cells and maintain the integrity of the intestinal barrier to prevent the bacterial and endotoxin translocation in SAP.


Asunto(s)
Apoptosis/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Pancreatitis Aguda Necrotizante/tratamiento farmacológico , Estilbenos/uso terapéutico , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Etiquetado Corte-Fin in Situ , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Microscopía Confocal , Pancreatitis Aguda Necrotizante/inducido químicamente , Pancreatitis Aguda Necrotizante/patología , Proteínas Proto-Oncogénicas c-bcl-2/genética , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Resveratrol , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Cloruro de Sodio , Estilbenos/farmacología , Proteína X Asociada a bcl-2/genética
20.
World J Gastroenterol ; 14(15): 2358-63, 2008 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-18416462

RESUMEN

AIM: To discuss the expression of alpha-adrenoreceptors in pancreatic cancer cell lines PC-2 and PC-3 and the effects of alpha1- and alpha2-adrenoreceptor antagonists, yohimbine and urapidil hydrochloride, on the cell lines in vitro. METHODS: We cultured the human ductal pancreatic adenocarcinoma cell lines PC-2 and PC-3 and analyzed the mRNA expression of alpha1- and alpha2-adrenergic receptors by reverse transcription polymerase chain reaction (RT-PCR). The effects of yohimbine and urapidil hydrochloride on cell proliferation were assessed by 3-(4,5-dimethylthiasol-2-yl)-2,4,-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected using the terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) assay and flow cytometry (FCM). RESULTS: PC-2 expressed mRNA in alpha1- and alpha2-adrenoreceptors. MTT assays showed that urapidil hydrochloride had no effect on PC-3 cell lines. However, exposure to urapidil hydrochloride increased DNA synthesis in PC-2 cell lines as compared to the control group. PC-2 cell lines were sensitive to both drugs. The proliferation of the 2 cell lines was inhibited by yohimbine. Cell proliferation was inhibited by yohimbine via apoptosis induction. CONCLUSION: The expression of alpha1- and alpha2-adrenoreceptors is different in PC-2 and PC-3 cell lines, which might be indicative of their different functions. The alpha2-adrenoceptor antagonist, yohimbine, can inhibit the proliferation of both cell lines and induce their apoptosis, suggesting that yohimbine can be used as an anticancer drug for apoptosis of PC-2 and PC-3 cells.


Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 2 , Antagonistas Adrenérgicos alfa/farmacología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias Pancreáticas/patología , Yohimbina/farmacología , Antagonistas de Receptores Adrenérgicos alfa 1 , Línea Celular Tumoral , Replicación del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica , Humanos , Etiquetado Corte-Fin in Situ , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Piperazinas/farmacología , ARN Mensajero/metabolismo , Receptores Adrenérgicos alfa 1/metabolismo , Receptores Adrenérgicos alfa 2/genética , Receptores Adrenérgicos alfa 2/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
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