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1.
Chinese Journal of School Health ; (12): 361-365, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-965858

RESUMEN

Objective@#To determine the knowledge, attitudes and practices (KAP) regarding tuberculosis prevention and control among college students in Wuhan, China, while analyzing the factors affecting tuberculosis prevention behavior.@*Methods@#Referring to the National KAP Questionnaire for Tuberculosis Prevention and Control among College Students, which was designed by China Center for Disease Control and Prevention, 22 colleges and universities in Wuhan were selected using a judgment sampling method, and a questionnaire survey was carried out through the online questionnaire platform. The formation of tuberculosis prevention and control behavior among this population was analyzed by single factor and multi factor Logistic regression.@*Results@#The total awareness rate of KAP regarding tuberculosis prevention and control among college students in Wuhan was 79.69%; the awareness rate of core knowledge was 79.28%, and the passing rate was 92.46%. The correct attitude holding rate was 89.69%, while the passing rate was 90.56%. In respect to correct behavior, the formation rate was 72.11%, with a passing rate of 96.62%. The multivariate Logistic regression analysis showed that the following factors were more likely to promote tuberculosis prevention and control behaviors that met the target: female college students ( OR =1.86); college students whose father had a primary school education level, junior high school and equivalent, high school and equivalent, and junior high school students ( OR =2.94, 3.05, 3.17, 3.24 ); no history of tuberculosis ( OR =3.32); the passing knowledge of core knowledge ( OR =9.91), and the passing attitude holding score ( OR =7.35)( P <0.05).@*Conclusion@#The overall awareness rate of KAP regarding tuberculosis prevention and control among college students in Wuhan is acceptable,the mainly influenced factors are gender, history of tuberculosis, awareness rate of core knowledge about prevention and control, attitudes and cognition, and parents educational background.

2.
Ann Hepatol ; 27(1): 100552, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34614432

RESUMEN

INTRODUCTION AND OBJECTIVES: Optimal treatment of hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) remains controversial. MATERIALS AND METHODS: A total of 627 HCC patients with PVTT after initial treatment with one of the following at Affiliated Tumor Hospital of Guangxi Medical University: liver resection (LR, n = 225), transarterial chemoembolization (TACE, n = 298) or sorafenib (n = 104) were recruited and randomly divided into the training cohort (n = 314) and internal validation cohort (n = 313). Survival analysis were repeated after stratifying patients by Cheng PVTT type. RESULTS: Resection led to significantly higher OS than the other two treatments among patients with type I or II PVTT. TACE worked significantly better than the other two treatments for patients with type III. All three treatments were associated with similar OS among patients with type IV. These findings were supported by the internal validation cohort. CONCLUSIONS: Our results suggest that the optimal treatment for HCC involving PVTT depends on the type of PVTT. LR may be more appropriate for type I or II PVTT; TACE, for type III Sorafenib may be more appropriate than invasive treatments for patients with type IV PVTT.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Hepatectomía/métodos , Neoplasias Hepáticas/terapia , Vena Porta , Sorafenib/administración & dosificación , Trombosis de la Vena/etiología , Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/terapia
3.
Biomed Pharmacother ; 125: 109972, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32036221

RESUMEN

Ephrin-2 (EFNB2) is expressed at abnormally high levels in some neoplasms, such as squamous cell carcinoma of the head and neck and colorectal cancer. Its overexpression is associated with the malignant progression of tumors. However, the expression of EFNB2 in pancreatic ductal adenocarcinoma (PDAC) has not been thoroughly studied. EFNB2 expression was evaluated by quantitative real-time PCR, immunohistochemistry, and western blotting. Furthermore, the association between its expression levels and the clinicopathological features of PDAC patients was explored. To determine the underlying mechanisms of EFNB2, we transfected PDAC cells with small interfering RNA and performed in vitro and in vivo experiments. EFNB2 expression levels were significantly increased in cancer tissues and were associated with PDAC clinical stage and Ki67 expression. The down-regulation of EFNB2 inhibited cell proliferation by up-regulating p53/p21-mediated G0/G1 phase blockade. Knockdown of EFNB2 decreased the migration and invasion of PDAC cells by blocking epithelial-mesenchymal transition. These results suggested that EFNB2 may participate in the development of PDAC by promoting cell proliferation, migration, and invasion. Thus, EFNB2 is a potential target for the diagnosis and treatment of PDAC.


Asunto(s)
Adenocarcinoma/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Efrina-B2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Quinasas p21 Activadas/metabolismo , Adenocarcinoma/genética , Carcinoma Ductal Pancreático/genética , Movimiento Celular , Proliferación Celular , Efrina-B2/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Proteína p53 Supresora de Tumor/genética , Quinasas p21 Activadas/genética
5.
Sci Rep ; 7(1): 185, 2017 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-28298641

RESUMEN

Postoperative pancreatic fistula (POPF) is a common complication following distal pancreatectomy (DP). However, the risk factors of this complication in patients after DP still remain controversial. The aim of our study is to estimate the association between potential risk factors and POPF. Relevant articles published up to June 21, 2016 were identified via PubMed, EMBASE, Web of Science, and The Cochrane Library. Studies that examined the risk factors of POPF following DP were enrolled. 20 articles (2070 patients) were finally included in this study. The pooled data suggested that patients with soft pancreas, higher Body Mass Index (BMI), blood transfusion, elevated intraoperative blood loss, and longer operative time had a decreased risk for POPF. However, age, gender, malignant pathology, types of stump closure, octreotide therapy, history of diabetes and chronic pancreatitis, splenectomy, multiorgan resection, main duct ligation, preoperative serum albumin levels, PGA felt wrapping, and extended lymphadenectomy could not be regarded as risk factors for POPF. Our analytic data demonstrated that pancreas texture, BMI, blood transfusion, intraoperative blood loss, and operative time were clinical predictor for POPF. This study may assist surgeons to screen patients with high risk of POPF and select appropriate treatment measures.


Asunto(s)
Pancreatectomía/efectos adversos , Fístula Pancreática/epidemiología , Complicaciones Posoperatorias/epidemiología , Femenino , Humanos , Masculino , Fístula Pancreática/etiología , Factores de Riesgo
6.
International Eye Science ; (12): 1878-1882, 2017.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-641085

RESUMEN

AIM: To compare the effect of small incision extracapsular cataract extraction and phacoemulsification on corneal endothelial cells and explore the differences between these two most commonly used surgeries for grade Ⅱ-Ⅲ lens nucleus. · METHODS: Retrospective study. We retrospectively evaluated the data of age-related cataract patients who had completed surgery in our hospital between June 2013 and December 2015. There were 84 eyes of 84 patients. The corneal endothelial cell density of all the patients were greater than 2000/mm2 and lens nucleus were gradeⅡ- Ⅲ. The patients were divided into manual small incision cataract surgery ( MSICS ) group and phacoemulsification ( Phaco ) group. MSICS group included 42 cases (42 eyes) and Phaco group included 42 cases ( 42 eyes ) . Postoperative evaluations were performed at 1d, 1wk, 1mo and 6mo and included uncorrected visual acuity ( UCVA ) , corneal endothelial cell density and the proportion of hexagonal cells. · RESULTS: There were no statistically significant differences of the two groups in preoperative basic data, UCVA, corneal endothelial cell density and the proportion of hexagonal cells, nuclear classification. The postoperative UCVA were significantly improved in both groups (x2=148. 01, P0. 05). ·CONCLUSION: Manual small incision cataract surgery and phacoemulsification can indiscriminately improve UCVA and decrease the density of corneal endothelial cells. However, the change of hexagonal cells proportion was not obvious. These two surgeries for cataract patients with corneal endothelial cell density greater than 2000/mm2 , grade Ⅱ-Ⅲ lens nucleus have similar efficacy and safety.

7.
BMC Cancer ; 14: 738, 2014 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-25274283

RESUMEN

BACKGROUND: Natural killer (NK) cells play a key role in non-specific immune response in different cancers, including pancreatic cancer. However the anti-tumor effect of NK cells decreases during pancreatic cancer progression. The regulatory pathways by which NK cells facilitate tumor immune escape are unclear, therefore our purpose was to investigate the roles of the contributory factors. METHODS: NK cells isolated from fresh healthy peripheral blood were co-cultured with normal human pancreatic ductal cells hTERT-HPNE and human pancreatic cancer cell lines SW1990 and BxPc-3 in vitro. Then NK cell function was determined by Flow cytometric analysis of surface receptors and cytotoxic granules in NK cells, NK cell apoptosis and cytotoxicity, and Enzyme-linked immunosorbent assay of cytokines. Expression level of MMP-9, IDO and COX-2 in hTERT-HPNE and SW1990 cells were detected by quantitative RT-PCR. Statistical differences between data groups were determined by independent t-tests using SPSS 19.0 software. RESULTS: Our results showed that NK cell function was significantly downregulated following exposure to pancreatic cancer cells compared to normal pancreatic cells, as demonstrated by lower expressions of activating surface receptors (NKG2D, DNAM-1, NKp30 and NKp46) and cytotoxic granules (Perforin and Granzyme B); decreased secretion of cytokines (TNF-α and IFN-γ); and reduced cytotoxicity against myelogenous leukemia K562 cells. Further investigations revealed that MMP-9 and IDO may be implicated in SW1990 cell-induced NK cell dysfunction by facilitating tumor immune evasion. Blockade by TIMP-1 and/or 1-MT could partially restore NK function. CONCLUSIONS: Taken together, elevation of MMP-9 and IDO induced by pancreatic cancer cells mediates NK cell dysfunction. Our findings could contribute to the development of NK cell-based immunotherapy in patients with pancreatic cancer.


Asunto(s)
Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/metabolismo , Apoptosis/inmunología , Línea Celular Tumoral , Células Cultivadas , Técnicas de Cocultivo , Citocinas/biosíntesis , Citotoxicidad Inmunológica , Humanos , Receptores de Superficie Celular/metabolismo
8.
Mol Cancer ; 13: 130, 2014 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-24884523

RESUMEN

BACKGROUND: Increasing evidence indicates an important role of transcription factor Yin Yang-1 (YY1) in human tumorigenesis. However, its function in cancer remains controversial and the relevance of YY1 to pancreatic ductal adenocarcinoma (PDAC) remains to be clarified. METHODS: In this study, we detected YY1 expression in clinical PDAC tissue samples and cell lines using quantitative RT-PCR, immunohistochemistry and western blotting. We also detected MUC4 and MMP10 mRNA levels in 108 PDAC samples using qRT-PCR and analyzed the correlations between YY1 and MUC4 or MMP10 expression. The role of YY1 in the proliferation, invasion and metastatic abilities of PDAC cells in vitro was studied by CCK-8 assay, cell migration and invasion assays. In vivo pancreatic tumor growth and metastasis was studied by a xenogenous subcutaneously implant model and a tail vein metastasis model. The potential mechanisms underlying YY1 mediated tumor progression in PDAC were explored by digital gene expression (DGE) sequencing, signal transduction pathways blockage experiments and luciferase assays. Statistical analysis was performed using the SPSS 15.0 software. RESULTS: We found that the expression of YY1 in PDACs was higher compared with their adjacent non-tumorous tissues and normal pancreas tissues. However, PDAC patients with high level overexpression of YY1 had better outcome than those with low level overexpression. YY1 expression levels were statistically negatively correlated with MMP10 expression levels, but not correlated with MUC4 expression levels. YY1 overexpression suppressed, whereas YY1 knockdown enhanced, the proliferation, invasion and metastatic properties of BXPC-3 cells, both in vitro and in vivo. YY1 suppresses invasion and metastasis of pancreatic cancer cells by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism. CONCLUSIONS: The present study suggested that YY1 plays a negative role, i.e. is a tumor suppressor, in PDAC, and may become a valuable diagnostic and prognostic marker of PDAC.


Asunto(s)
Carcinoma Ductal Pancreático/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Metaloproteinasa 10 de la Matriz/genética , Neoplasias Pancreáticas/genética , Factor de Transcripción YY1/genética , Adulto , Anciano , Anciano de 80 o más Años , Animales , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/secundario , Femenino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/secundario , Factores de Transcripción MEF2/genética , Factores de Transcripción MEF2/metabolismo , Masculino , Metaloproteinasa 10 de la Matriz/metabolismo , Ratones , Ratones Desnudos , Persona de Mediana Edad , Mucina 4/genética , Mucina 4/metabolismo , Páncreas/metabolismo , Páncreas/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Transducción de Señal , Análisis de Supervivencia , Ensayos Antitumor por Modelo de Xenoinjerto , Factor de Transcripción YY1/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
9.
International Eye Science ; (12): 1513-1515, 2014.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-641919

RESUMEN

AIM: To observe the therapeutic effect of combined trabeculectomy with improved conjunctival incision at 1mm of corneoscleral limbus posterior METHODS: A retrospective analysis of 171 cases ( 220 eyes ) with primary glaucoma who were randomly divided into 3 groups according to the differences of conjunctival incision and the way of suture. Group A:44 eyes of 33 cases underwent corneoscleral limbus conjunctival incision; Group B: 94 eyes of 76 cases underwent conjunctival incision at 1mm of corneoscleral limbus posterior; Group C: 82 eyes of 62 cases underwent conjunctival flap running suture based on group B. All cases were followed up for 1a. Intraocular pressure, morphology of filtering bleb, depth of anterior chamber and water leakage in conjunctival incision were observed and compared after operation among three groups. RESULTS: The incidence of postoperative water leakage inconjunctival incision and shallow anterior chamber were group A >group B>group C and there were significant differences among the three groups ( PCONCLUSION: Conjunctival incision at 1mm of corneoscleral limbus posterior and conjunctival flap running suture can not only reduce the rate of water leakage in conjunctival incision and accelerate the speed of incision adhesion after operation, but also significantly enhance the therapeutic effect of combined trabeculectomy.

10.
J Transl Med ; 11: 262, 2013 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-24138752

RESUMEN

BACKGROUND: Digestive malignancies, especially pancreatic cancer (PC), gastric cancer (GC), and colorectal cancer (CRC), still occur at persistently high rates, and disease progression in these cancers has been associated with tumor immunosurveillance escape. Natural killer (NK) cell dysfunction may be responsible for this phenomenon, however, the exact relationship between tumor immunosurveillance escape in digestive malignancies and NK cell dysfunction remains unclear. METHODS: Percentage of the surface receptors NKG2A, KIR3DL1, NKG2D, NKp30, NKp44, NKp46, and DNAM-1, as well as the cytotoxic granules perforin and granzyme B positive NK cells were determined in patients with pancreatic cancer (n=31), gastric cancer (n=31), and CRC (n=32) prior to surgery and healthy controls (n=31) by multicolor flow cytometry. Independent t-tests or Mann-Whitney U-tests were used to compare the differences between the patient and healthy control groups, as well as the differences between patients with different pathologic features of cancer. RESULTS: Percentage of NKG2D, NKp30, NKp46, and perforin positive NK cells was significantly down-regulated in patients with PC compared to healthy controls, as well as GC and CRC; reduced levels of these molecules was associated with indicators of disease progression in each malignancy (such as histological grade, depth of invasion, lymph node metastasis). On the contrary, percentage of KIR3DL1 positive NK cells was significantly increased in patients with PC, as well as GC and CRC, but was not associated with any indicators of disease progression. CONCLUSIONS: Altered percentage of surface receptors and cytotoxic granules positive NK cells may play a vital role in tumor immunosurveillance escape by inducing NK cell dysfunction in patients with PC, GC, and CRC.


Asunto(s)
Neoplasias Colorrectales/metabolismo , Gránulos Citoplasmáticos/metabolismo , Células Asesinas Naturales/metabolismo , Neoplasias Pancreáticas/metabolismo , Receptores de Superficie Celular/metabolismo , Neoplasias Gástricas/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad
11.
Yao Xue Xue Bao ; 47(3): 374-9, 2012 Mar.
Artículo en Chino | MEDLINE | ID: mdl-22645762

RESUMEN

Unusual dTDP-sugars are key intermediate in many pathogenic bacteria. In this study, negative-ion electrospray tandem mass spectrometry (ESI-MS-MS) with collision-induced dissociation (CID) was used to study the fragmentation characteristics of six unusual nucleotide diphosphate sugars. The results indicated the major fragment of the six unusual nucleoside sugars observed in the ESI-MS-MS spectra resulted from cleavage of diphosphate moiety and their characteristic fragment ions at m/z 401, 383, and 321, correspond to [TDP-H] together with fragment ions resulting from the loss of water and phosphate moiety, respectively. Furthermore, 4-position substituted change of unusual sugar rings affected the stability of two important characteristic fragment ions of [glycosyl-1"-PO3](-) and [glycosyl-1"-P2O6](-).


Asunto(s)
Azúcares de Nucleósido Difosfato/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodos , Estructura Molecular , Azúcares de Nucleósido Difosfato/síntesis química
12.
Clin Transl Oncol ; 14(2): 116-24, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22301400

RESUMEN

INTRODUCTION: Epigenetic modifications play an important role in multistage carcinogenesis. The role of the three functional DNA methyltransferases (DNMTs) in pancreatic carcinogenesis has not been fully understood. The main goal of this study was to examine DNMT expression in different stages of pancreatic ductal adenocarcinoma (PDAC), and evaluate their prognostic significance in PDAC. MATERIALS AND METHODS: A large number of premalignant and malignant pancreatic lesions were obtained by manual microdissection. Quantitative real-time RT-PCR was used to detect DNMTs mRNA expression. Nonparametric test, logrank test and Cox regression analysis were used to evaluate the clinical significance of DNMT expression. RESULTS: The mRNA expression of the three DNMTs increased with the development of pancreatic cancer from normal duct to pancreatic intraductal neoplasia and further to PDAC, and were statistically correlated with each other. Expression of the three DNMTs was statistically correlated with TNM staging and history of chronic pancreatitis. DNMT3A and DNMT3B, but not DNMT1 expression, was statistically correlated with tumour size. Patients with higher levels of DNMT1, DNMT3A and/or DNMT3B expression had an overall lower survival than those with lower levels of expression. Univariate analysis showed that high expression levels of DNMTs, alcohol consumption, tumour differentiation and TNM staging were statistically significant risk factors. Multivariate analysis showed that high level of DNMT3B expression and tumour differentiation were statistically significant independent poor prognostic factors. CONCLUSIONS: These results suggested that pancreatic carcinogenesis involves an increased mRNA expression of three DNMTs, and they may become valuable diagnostic and prognostic markers as well as potential therapeutic targets for pancreatic cancer.


Asunto(s)
Adenocarcinoma/genética , Carcinoma Ductal Pancreático/genética , ADN (Citosina-5-)-Metiltransferasas/genética , Neoplasias Pancreáticas/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , ADN (Citosina-5-)-Metiltransferasa 1 , ADN Metiltransferasa 3A , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Páncreas/metabolismo , Páncreas/patología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Tasa de Supervivencia , Resultado del Tratamiento , ADN Metiltransferasa 3B
13.
Swiss Med Wkly ; 141: w13208, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21630164

RESUMEN

BACKGROUND: The hedgehog (Hh) pathway has been implicated in the pathogenesis of cancer including pancreatic ductal adenocarcinoma (PDAC). Recent studies have suggested that Hh plays an important role in maintaining the cancer stem cell (CSCs) pool. Gemcitabine-resistant pancreatic cancer cells highly express some of the CSCs markers. However, the expression level of Hh members in gemcitabine-resistant pancreatic cancer cells remains unknown. The aim of this study was to verify the expression of HH members, such as Shh, Ptc, SMO and Gli-1 in gemcitabine-resistant PDAC cell lines, and to explore a new strategy to overcome chemoresistance in PDAC. MATERIAL AND METHODS: Quantitative real-time RT-PCR (Q-PCR) and western blot were used to evaluate the relative expression level of HH members in SW1990, CFPAC-1 cells and gemcitabine-resistant SW1990, CFPAC-1 cells. The change of cancer stem cell markers and the expression level of HH members before and after cyclopamine treatment was evaluated using flow cytometry and Q-PCR, western blot, respectively. Cell apoptosis after cyclopamine treatment was measured by flow cytometry. RESULTS: CD44, CD133 and the expression level of HH members, including Shh, SMO, Gli-1, were found to be highly expressed in gemcitabine-resistant cells, which were significantly down-regulated by cyclopamine treatment. Flow cytometry analysis showed increased cell apoptosis after cyclopamine treatment. CONCLUSION: Gemcitabine-resistant pancreatic cancer cells highly express CSCs markers and some of the HH members, and inhibition of HH by cyclopamine is an effective method of reversing gemcitabine resistance in pancreatic cancer.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Neoplasias Pancreáticas/metabolismo , ARN Mensajero/metabolismo , Alcaloides de Veratrum/farmacología , Antígeno AC133 , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1 , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Antígenos CD/metabolismo , Apoptosis , Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Regulación hacia Abajo , Glicoproteínas/metabolismo , Proteínas Hedgehog/metabolismo , Humanos , Receptores de Hialuranos/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas Oncogénicas/genética , Proteínas Oncogénicas/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Receptores Patched , Péptidos/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal , Receptor Smoothened , Transactivadores/genética , Transactivadores/metabolismo , Células Tumorales Cultivadas , Proteína con Dedos de Zinc GLI1 , Gemcitabina
14.
Zhonghua Wai Ke Za Zhi ; 48(18): 1416-24, 2010 Sep 15.
Artículo en Chino | MEDLINE | ID: mdl-21092580

RESUMEN

OBJECTIVES: To identify HLA-restricted epitope of mucoprotein 4 (MUC4) antigen as a tumor associated antigen of pancreatic ductal adenocarcinoma (PDAC), and to validate its natural presentation in PDAC patient peripheral blood. METHODS: Two epitope prediction databases (SYFPEITHI and ProPred-I) were used to predict HLA-A*0201 restricted MUC4 epitope, T2 cell assay was used to determine the peptide binding affinity with HLA-A*0201 molecule. Dendritic cells (DCs) were induced from the HLA-A* 0201-positive healthy individuals' peripheral blood mononuclear cells (PBMC). Mature DCs were pulsed with synthesized peptides. Autologous CD8(+) T cells from the HLA-A* 0201 healthy donor were stimulated with the peptide-pulsed DCs as CTL. CTL activity was assessed by lactate dehydrogenase release assay and IFN-γ released by enzyme-linked immunospot assay. Pentamer was synthesized for HLA-A* 0201 restricted epitope P1126, then was used to detect specific CTL in PBMC of PDAC patients. RESULTS: Five candidate HLA-A*0201 epitopes were predicted, LLLGVGTFV (P1125) and LLGVGTFVV (P1126) were determined as the two with more HLA-A*0201 affinity. Mature DCs could be induced from PBMCs. CTL induced by peptide P1126 could lyses T2 cells pulsed with peptide P1126 and HCT-116 cells [MUC4(+), HLA-A2(+)]. The number of CTL induced by peptide P1126 which could secret IFN-γ (130.3 ± 6.6) was obviously higher than that in the negative group. By Pentamer assay, P1126-pentamer and CD8 double positive CTL could be detected in PBMC of PDAC patients with MUC4(+) than patients with MUC4(-), but no significant difference of CTL frequency between patients with HLA-A2(+) and with HLA-A2(-) in MUC4(+) PDAC patients. CONCLUSIONS: Tumor associated antigen MUC4-derived HLA-A* 0201-restrictive cytotoxic T lymphocyte (CTL) epitope P1126 can induce CTL reaction. The CTL can secret immunologic active material to induce the specific target cells lysis. P1126 epitope can be naturally presented in PBMC of PDAC patients, but its HLA-restriction may not be perfect.


Asunto(s)
Antígenos de Neoplasias/inmunología , Epítopos de Linfocito T/inmunología , Mucina 4/inmunología , Neoplasias Pancreáticas/inmunología , Células Cultivadas , Células Dendríticas/inmunología , Antígenos HLA-A/inmunología , Antígeno HLA-A2/inmunología , Humanos , Linfocitos T Citotóxicos/inmunología
15.
Oncol Rep ; 23(5): 1375-82, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20372854

RESUMEN

In this study, we first sought to determine the existence of side population (SP) cells in pancreatic cancer cell lines. Furthermore, we compared the biological characteristics of SP and non-SP cells. The presence of side population cells in pancreatic cancer cell lines was detected by Hoechst 33342 staining and FACS analysis. Cell cycle distribution was analyzed using flow cytometry. SP and non-SP cells were exposed to various concentrations of gemcitabine; drug sensitivity was examined using the MTT assay and flow cytometry using Annexin-V and PI staining. To compare the tumorigenic ability in vivo, groups of nude mice were orthotopically inoculated with varying numbers of SP and non-SP cells. The percentages of CD44+CD24+ and CD133+ in SP and non-SP cells were also detected by FACS analysis. The SP fraction was detected in BxPc-3, CFPAC-1, MIA PaCa-2, PANC-1 and SW1990 pancreatic cancer cell lines. Cell cycle analysis revealed that the SP cells contained more cells in the G1 phase and fewer cells in the S phase when compared with the non-SP cells. The SP cells exhibited increased tumorigenetic ability following in vivo transplantation into BALB/C nude mice and increased chemoresistance following in vitro exposure to gemcitabine. FACS analysis showed that the SP cells contained more CD44+CD24+ and CD133+ cells than the non-SP cells. In conclusion, these observations suggest that SP cells in the pancreatic cancer cell lines possess the property of cancer stem cells. SP cells may therefore be novel specific targets for the effective treatment of pancreatic cancer.


Asunto(s)
Células Madre Neoplásicas/patología , Neoplasias Pancreáticas/patología , Antígeno AC133 , Animales , Antígenos CD/análisis , Antimetabolitos Antineoplásicos/farmacología , Apoptosis , Antígeno CD24/análisis , Ciclo Celular , Diferenciación Celular , Línea Celular Tumoral , Proliferación Celular , Separación Celular , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica , Glicoproteínas/análisis , Humanos , Receptores de Hialuranos/análisis , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/inmunología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/inmunología , Péptidos/análisis , Factores de Tiempo , Carga Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Gemcitabina
16.
Zhonghua Wai Ke Za Zhi ; 47(5): 326-8, 2009 Mar 01.
Artículo en Chino | MEDLINE | ID: mdl-19595003

RESUMEN

OBJECTIVE: To evaluate the methods of diagnosis and surgical treatment for nonfunctional islet cell tumor (NICT). METHODS: Forty-four patients with non-functional islet cell tumor treated at the First Affiliated Hospital of Nanjing Medical University during January 1968 to June 2008 were analyzed retrospectively. There were 9 males and 35 females, aged from 7- to 70-years-old. Clinical manifestation: 15 cases (34.1%) of abdominal masses, 17 patients (38.6%) with epigastric or back pain, 5 cases of jaundice, 5 cases (11.4%) for upper abdominal fullness or vomiting, 10 cases (22.7%) of pancreatic tumor noticed by routine health checkups or imaging examinations. Imaging examination: CT scan, sonography, ERCP, MRI, upper GI series were performed in 33 (75.0%), 16 (36.4%), 6 (13.6%), 2 (4.5%), and 10 cases (22.7%) respectively. Operation methods: 39 patients (88.6%) underwent surgical resection and the other 5 patients did not. COMPLICATIONS: pancreatic fistula in 7 patients (15.9%), intra-abdominal bleeding in 4 (9.1%), gastrojejunal anastomosis outlet obstruction in 1 (2.3%), biliary fistula in 2 (4.5%) and incisional infection in 3 (6.8%). Surgery related mortality happened in 2 patients (4.5%), both treated before 1999. Twenty-five patients underwent operation between January 1999 and June 2008 were followed up for 6 to 108 months. All survive except one died 75 months after the surgery for unknown reason. CONCLUSIONS: No specific clinical manifestation is recognized for non-functional islet cell tumor. Spiral CT is an optimal diagnostic method, while surgery is the first choice for treatment. Middle segmental pancreatectomy has become an alternative surgical protocol for NICT.


Asunto(s)
Adenoma de Células de los Islotes Pancreáticos/diagnóstico , Adenoma de Células de los Islotes Pancreáticos/cirugía , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirugía , Adolescente , Adulto , Anciano , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pancreatectomía/métodos , Pronóstico , Estudios Retrospectivos , Adulto Joven
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