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1.
Zhen Ci Yan Jiu ; 45(4): 330-3, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32333541

RESUMO

OBJECTIVE: To observe the clinical effectiveness of Jingjin (muscle region) needling in the treatment of Hunt facial paralysis (HFP). METHODS: A total of 80 HFP patients were randomly divided into acupuncture and medication groups (n=40 cases/group). Jingjin needling was applied to Yangbai(GB14) to Shangxing (GV23), Touwei (ST8), Cuanzhu (BL2), Sizhukong (TE23,penetrative needling), Dicang (ST4) to Jiache (ST6, penetrative needling), Yingxiang(LI20) and Xiaguan(ST7), Hegu(LI4), Yifeng (TE17), Yuyao (EX-HN 4), and Shenmai (BL62), with the needles retained for 30 min. The treatment was conducted once daily, with 10 consecutive days being a therapeutic course, and 3 courses altogether. Patients of the medication group received oral administration of Prednisone acetate (12 days), Acyclovir (7 days), intramuscular injection of Vitamin B12 and Vitamin B1(10 days), then, oral administration of Vitamin B1, successively. The therapeutic effect was assessed by using House-Brackman (H-B) facial function grading system (grade I to VI), traditional Chinese medicine (TCM) sign and symptom score, and facial disability index (FDI) scale including FDI physical function (FDIP, food and water swallowing, speaking-pronouncing, dryness or tearing, and mouth-opening) and FDI social function (FDIS, self-rating anxiety/depression scales), separately. RESULTS: After the treatment, the TCM symptom and sign scores for depth of nasolabial groove, nose shrugging, lower lip asymmetry, food retention and post-auricular pain were significantly lower in the medication group (P<0.05).After the treatment, the TCM symptom and sign scores for frontal muscle movement, eyelid opening and closing, depth of nasolabial groove, nose shrugging, lower lip asymmetry, cheek blowing, food retention, latissimus cervicalis contraction, taste disorder, hearing hypersensitivity, tears and discomfort and post-auricular pain were significantly lower in the acupuncture group (P<0.05).Comparison between two groups showed that the TCM symptom and sign scores for frontal muscle movement, eyelid opening and closing, depth of nasolabial groove, nose shrugging, lower lip asymmetry, cheek blowing, food retention, latissimus cervicalis contraction, taste disorder, hearing hypersensitivity, tears and discomfort and post-auricular pain were significantly lower in the acupuncture group than in the medication group(P<0.05).The scores of FDIP and FDIS were significantly increased in both groups (P<0.01) and notably higher in the acupuncture group than in the medication group (P<0.01) after the treatment. The total effective rate of acupuncture group was 97.5% (39/40), and that of medication group was 72.5% (29/40). The therapeutic effect of the acupuncture group was significantly superior to that of the medication group (P<0.01).. CONCLUSION: Jingjin needling has a good therapeutic effect in improving facial nerve function, psychosomatic function and clinical signs and symptoms in HFP patients, evidently being better than medication.

2.
World J Gastroenterol ; 26(8): 828-838, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32148380

RESUMO

BACKGROUND: Systemic inflammation and nutrition status play an important role in cancer metastasis. The combined index of hemoglobin, albumin, lymphocyte, and platelet (HALP), consisting of haemoglobin, albumin, lymphocytes, and platelets, is considered as a novel marker to reflect both systemic inflammation and nutrition status. However, no studies have investigated the relationship between HALP and survival of patients with pancreatic cancer following radical resection. AIM: To evaluate the prognostic value of preoperative HALP in pancreatic cancer patients. METHODS: The preoperative serum levels of hemoglobin, albumin, lymphocyte counts, and platelet counts were routinely detected in 582 pancreatic adenocarcinoma patients who underwent radical resection. The relationship between postoperative survival and the preoperative level of HALP was investigated. RESULTS: Low levels of HALP were significantly associated with lymph node metastasis (P = 0.002), poor tumor differentiation (P = 0.032), high TNM stage (P = 0.008), female patients (P = 0.005) and tumor location in the head of the pancreas (P < 0.001). Low levels of HALP were associated with early recurrence [7.3 mo vs 16.3 mo, P < 0.001 for recurrence-free survival (RFS)] and short survival [11.5 mo vs 23.6 mo, P < 0.001 for overall survival (OS)] in patients with resected pancreatic adenocarcinoma. A low level of HALP was an independent risk factor for early recurrence and short survival irrespective of sex and tumor location. CONCLUSION: Low levels of HALP may be a significant risk factor for RFS and OS in patients with resected pancreatic cancer.

3.
Nanoscale ; 12(12): 6852-6860, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32186547

RESUMO

Regulating the fluorescence of carbon dots (CDs) is important but highly challenging. Here, carbon dots with tunable dual emissions were facilely fabricated via modulating the polymerization and carbonization processes of o-phenylenediamine (OPD) with lysine (Lys) as the co-precursor and modulator, respectively. The self-polymerization/carbonization of the OPD molecules contributed to the blue/green emission of the OPD-derived CDs. The introduction of Lys in the CD fabrication process efficiently suppressed the carbonization of the OPD polymer chains and enhanced the self-polymerization of the OPD molecules. Meanwhile, the formed OPD-Lys co-polymer chains endowed the final CD product with a new green emission center. The dual-emissive CDs were distinctly sensitive to polarity fluctuations, providing a ratiometric fluorescence response towards solution polarity. Due to their specific distribution in the endoplasmic reticulum (ER), the as-prepared dual-emissive CDs successfully distinguished the polarity variations in ER under stress, which offers a new approach for the early diagnosis of cell injury.

4.
Brain Res Bull ; 157: 149-161, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32044361

RESUMO

Improvised explosive devices (IEDs) represent the leading causes for casualties among civilians and soldiers in the present war (including counter-terrorism). Traumatic brain injury (TBI) caused by IEDs results in different degrees of impairment of cognition and behavior, but the exact brain pathophysiological mechanism following exposure to blast has not been clearly investigated. Here, we sought to establish a rat model of closed-head blast injury using compressed gas to deliver a single blast only to the brain without systemic injuries. The cognitive functions of these bTBI models were assessed by Morris Water Maze test (MWM test). The HE staining, flow cytometry, ELISA and Western Blotting were used to measure the effects of shock wave on general histology, regulatory T (Treg) cells percentage, inflammatory reactions, the expression and phosphorylation level of tau, respectively. In addition, the brain water content and 24 -h mortality were also assessed. As the distance from the blast source increased, the input pressure did not change, the overpressure decreased, and the mortality decreased. Receiver operating characteristic (ROC) curves for predicting 24 -h mortality using peak overpressure fits with the following areas under ROC curves: 0.833. In 2 weeks after blast injury, cognitive tests revealed significantly decreased performance at 20 cm distance from the blast (about 136.44 kPa) as demonstrated by increased escape latency in the acquisition phase, and decreased crossing numbers in the probe phase of MWM test. Interestingly, a single blast exposure (at 20 cm) lead to significantly increased tau phosphorylation at the Thr205 epitope but not at the Ser404 and Ser262 epitopes at 12 h, 24 h, 3d, and 7d after blast injury. Blast decreased the percentage of CD4+T cells, CD8+T cells, Treg cells and lymphocytes at different time points after blast injury, and blast increased the percentage of neutrophils at 12 h after blast injury and significantly increased IL-6 production at 12 h, 24 h and 3d after blast injury. In addition, blast lead to an increase of brain edema at 24 h and 3d after blast injury. However, no obvious alterations in brain gross pathology were found acutely in the blast-exposed rats. In conclusion, we established a rat model of simple craniocerebral blast injury characterized by impairment of cognitive function, Thr205 phosphorylation of tau, decreased Treg cells and increased inflammatory reactions and brain edema. We expect this model may help clarify the underlying mechanism after blast injury and possibly serve as a useful animal model in the development of novel therapeutic and diagnostic approaches.

5.
J Org Chem ; 85(2): 327-338, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31799851

RESUMO

A novel approach has been constructed for the synthesis of two types of 2-amino-4-coumarinyl-5-arylpyrroles (ACAPs, 5 and 6) through a cascade reaction and a metal-free catalyzed aerobic oxidation reaction of arylglyoxal monohydrates 1, 1,1-enediamines (EDAMs) 2 and 3, and 4-hydroxy-2H-chromen-2-ones 4 via multicomponent reactions to produce the target compounds with good to excellent yields. Specifically, hydroxyl-substituted 2-amino-4-coumarinyl-5-arylpyrroles, that is, 2-amino-4-coumarinyl-5-aryl-6-hydroxylpyrroles (ACAHPs) 6, were obtained by metal-free aerobic oxidation in 1,4-dioxane at simple reflux for approximately 10 h. As a result, ACAHPs 6 have been produced without metal catalysts or traditional oxidizing agents. This method represents a route to obtain the novel ACAPs in an environmentally friendly, concise, rapid, and practical manner with potential biological activity of the product.

6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 643-648, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762231

RESUMO

OBJECTIVE: To study the regulation role and mechanism of protein acetylation on the expression of glioblastoma-derived neurotrophic factor (GDNF) in human glioma. METHODS: Six normal brain tissue samples, six low-grade glioma brain tissue (LG-glioma), and six high-grade glioma brain tissue (HG-glioma) were collected for study. Human glioma U251 cells were treated with histone acetylase inhibitor and histone deacetylase inhibition. The mRNA level of GDNF in glioma and normal controls was detected by Real-time PCR. H3K9 acetylation level of cAMP-response element binding protein (CREB) binding region on GDNF promoter and the ability of CREB combining to GDNF promoter were detected by ChIP-PCR. The effects of histone acetylase and deacetylase inhibitors on transcription factor binding ability and GDNF expression were detected. RESULTS: The mRNA level of GDNF in HG-glioma was significantly higher than those in normal brain tissue and LG-glioma (P < 0.01). The H3K9 acetylation level of GDNF promoter region in the glioma was increased compared to that in the normal brain tissue (P < 0.01), and the acetylation level in CREB-binding region on the GDNF promoter was higher than that in the non-CREB-binding region (P < 0.01). The binding activity of CREB and GDNF promoter in HG-glioma was higher than those in normal brain tissue and LG-glioma (P < 0.05). After treatment of U251 cells with histone acetyltransferase inhibition, the level of acetylation in CREB-binding region on GDNF promoter, the binding activity of CREB and GDNF promoter was decreased, and GDNF transcription and expression were down-regulated, while histone deacetylase inhibitors had the opposite effect (P < 0.01). CONCLUSION: Histone acetylation promotes the transcription expression of GDNF in glioma by promoting the binding of transcription factor CREB to the promoter region of GDNF gene.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Glioma/metabolismo , Histonas/química , Acetilação , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Glioma/genética , Histona Acetiltransferases , Inibidores de Histona Desacetilases/farmacologia , Humanos , Regiões Promotoras Genéticas , Transcrição Genética
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1678-1681, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607331

RESUMO

OBJECTIVE: To analyze the diagnostic value of (1, 3) -ß-D-glucan and galactomannan (GM) tests in the patients with acute leukemia complicated by invasive fungal disease, and explore the application of serological detection (G/GM) and lung CT for early diagnosis of invasive fungal disease (IFD). METHODS: A total of 493 patients with acute leukemia complicated by high risk invasive fungal infection, also receival G and GM tests, in Department of hematology of our hospital from June 2016 to December 2016 were selected and were divided into IFD-confirmed group (62 cases) including confirmed and clinical diagnesed IFD, and IFD-unconfirmed group (431 cases) including suspected IFD and non-IFD according to the diagnostic criteria of IFD. The results of G and GM tests in patients of 2 groups were analyzed, then the diagnostic efficacy of G and GM done and combination evaluated. In addition, 26 patients whose lung CT negative at hospitalization, moreover, presentation of changes in lung by CT during hospitalization and serological G and GM test positive were selected, and the difference of time between serological that postive and presentation of changes in lung by CT were compared for the estimation of early diagnotic value. RESULTS: The positive rate of (1, 3) -ß-D-glucan in IFD-confirmed group and IFD-unconfirmed group was 56.5% and 10.4%, respectively. Meanwhile, that of galactomannan test was 41.9% and 9.0%, respectively. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of (1, 3) -ß-D-glucan was 56%, 90%, 44% and 92%, and that of galactomannan was 42%、91%、40% and 93%, respectively. Moreover, the combination of (1, 3) -ß-D-glucan and galactomannan could raise the sensitivity to 69% and specificity to 98%. The positive results of serological detection (G/GM) come earlier about five days than CT changes. CONCLUSION: Both (1, 3) -ß-D-glucan and galactomannan test have high sensitivity and specificity, and the combination of them can improve the diagnostic efficacy, and make the clinical antifungal therapy more precisely. In the early clinical diagnosis of IFD, the positive results of serological detection coming earlier than lung CT.


Assuntos
Infecções Fúngicas Invasivas , Leucemia Mieloide Aguda , Humanos , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/etiologia , Leucemia Mieloide Aguda/complicações , Mananas
9.
ACS Omega ; 4(2): 2863-2873, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-31459516

RESUMO

A novel approach has been developed for the synthesis of three kinds of highly functionalized 2-aminopyridine derivatives (APDs) through a three-component reaction of 1,1-enediamines (EDAMs) 1, N,N-dimethylformamide dimethyl acetal (DMF-DMA) 2, and 1,3-dicarbonyl compounds 3-5 via a base-promoted cascade reaction, producing the desired products in good to excellent yields. This method represents a route to obtain a novel class of APDs in a concise, rapid, and practical manner. This approach is particularly attractive because of the following features: low cost, mild temperature, atom economy, high yields, and potential biological activity of the product.

10.
J Cancer ; 10(12): 2670-2678, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31258775

RESUMO

Introduction: SRPX2 and RAB31 play important roles in tumorigenesis and metastasis; however, their prognostic value in pancreatic cancer remains unclear. This study aimed to investigate the potential interactions and effects of SRPX2 and RAB31 on the diagnosis and prognosis of pancreatic cancer. Methods: The expression of SRPX2 and RAB31 in pancreatic tumor tissues and cells was evaluated through database mining of the Oncomine, Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, and validated the results through immunohistochemistry (IHC) and Western blot in our clinical database. Protein-protein interactions were explored by immunofluorescence and Co-immunoprecipitation (Co-IP). Two hundred tissue microarray specimens from patients (79 training and 121 validation), who underwent curative pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) were used. Additionally, the association between the SRPX2 and RAB31 and prognosis of PDAC patients after surgery was analyzed. Results: The expression of SRPX2 and RAB31 was highly increased in pancreatic cancer, and there was a significant positive correlation between these two proteins. Co-IP showed the direct interaction between SRPX2 and RAB31. Kaplan-Meier analysis showed that positive expression of SRPX2 and RAB31 was associated with reduced disease-free survival (DFS) and overall survival (OS) of PDAC patients in the training set and the validation sets. Furthermore, multivariate analysis indicated that the 8th edition TNM stage and combination of SRPX2 and RAB31 were independent prognostic factors that associated with OS and DFS in the training, and the validation sets, respectively. Conclusions: The combination of SRPX2 and RAB31 can be important markers for the prognosis of pancreatic cancer.

11.
Proc Biol Sci ; 286(1900): 20182859, 2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-30966990

RESUMO

Self-organized spatial patterns are increasingly recognized for their contribution to ecosystem functioning, in terms of enhanced productivity, ecosystem stability, and species diversity in terrestrial as well as marine ecosystems. Most studies on the impact of spatial self-organization have focused on systems that exhibit regular patterns. However, there is an abundance of patterns in many ecosystems which are not strictly regular. Understanding of how these patterns are formed and how they affect ecosystem function is crucial for the broad acceptance of self-organization as a keystone process in ecological theory. Here, using transplantation experiments in salt marsh ecosystems dominated by Scirpus mariqueter, we demonstrate that scale-dependent feedback is driving irregular spatial pattern formation of vegetation. Field observations and experiments have revealed that this self-organization process affects a range of plant traits, including shoot-to-root ratio, rhizome orientation, rhizome node number, and rhizome length, and enhances vegetation productivity. Moreover, patchiness in self-organized salt marsh vegetation can support a better microhabitat for macrobenthos, promoting their total abundance and spatial heterogeneity of species richness. Our results extend existing concepts of self-organization and its effects on productivity and biodiversity to the spatial irregular patterns that are observed in many systems. Our work also helps to link between the so-far largely unconnected fields of self-organization theory and trait-based, functional ecology.

12.
J Exp Biol ; 222(Pt 8)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30952687

RESUMO

The metabolism of a living organism (e.g. bacteria, algae, zooplankton) requires a continuous uptake of nutrients from the surrounding environment. However, within local spatial scales, nutrients are quickly used up under dense concentrations of organisms. Here, we report that self-spinning dinoflagellates Symbiodinium sp. (clade E) generate a microscale flow that mitigates competition and enhances the uptake of nutrients from the surrounding environment. Our experimental and theoretical results reveal that this incessant active behavior enhances transport by approximately 80-fold when compared with Brownian motion in living fluids. We found that the tracer ensemble probability density function for displacement is time-dependent, but consists of a Gaussian core and robust exponential tails (so-called non-Gaussian diffusion). This can be explained by interactions of far-field Brownian motions and a near-field entrainment effect along with microscale flows. The contribution of exponential tails sharply increases with algal density, and saturates at a critical density, implying a trade-off between aggregated benefit and negative competition for the spatially self-organized cells. Our work thus shows that active motion and migration of aquatic algae play key roles in diffusive transport and should be included in theoretical and numerical models of physical and biogeochemical ecosystems.

13.
Sci Rep ; 9(1): 3113, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30816133

RESUMO

A limited number of studies have explored whether the role of circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in the pathogenesis of acute myocardial infarction (AMI) is sex specific. The purpose of the present study was to examine sex differences in plasma PCSK9 in Chinese patients with AMI. In this study, a total of 281 records from patients presenting with AMI were analyzed.We compared hospital data and plasma PCSK9 levels by sex difference for inpatients presenting with AMI. After 1 year of follow-up, major adverse cardiac events(MACE) were recorded. A Cox proportional hazards model was used to calculate hazard ratios with 95% confidence intervals. We found that, compared with male groups, PCSK9 levels were higher in female patients not only for overall patients with AMI but also for patients with ST-elevation myocardial infarction (STEMI) (median: 273.6 [215.6-366.8] vs. 325.1 [247.5-445.3] ng/ml, P = 0.0136; 273.4 [215.6-369.7] vs. 317.1 [249.6-450.1], P = 0.0275, respectively). The cumulative incidence of cardiac death and 1-year MACE were significantly higher in the female group compared with male group (10% vs. 2.74%, P = 0.025; 15% vs. 4.11%, P = 0.0054, respectively). On multivariate Cox regression analysis, female sex, total triglyceride, glycosylated hemoglobin A, and homocysteic acid were independent risk factors of 1-year MACE. There was no significant correlation between PCSK9 and 1-year MACE in total AMI patients. In conclusion, PCSK9 levels and 1-year MACE were higher in women with AMI than in men with AMI, however, female sex but not PCSK9 were significant correlated with the 1-year MACE. The clinical implications of this finding are worthy of further investigations and must be confirmed in larger cohorts.

14.
Onco Targets Ther ; 12: 309-317, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30643429

RESUMO

Objective: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of cells derived from bone marrow, which has a significant ability in inhibition of immune cell response. In this study, the role of miR-6991-3p in regulating function of MDSCs was investigated. Methods: MDSCs were isolated from different tissues of the control and hepatoma-bearing mice, and then expression of miR-6991-3p was detected with qPCR. Then, the miR-6991-3p mimic and inhibitor were respectively transfected into MDSCs, and behaviors of MDSCs were evaluated, including expansion, apoptosis, and production of inflammatory factors. Furthermore, we explored the underlying mechanism from which miR-6991-3p regulated MDSC functions. Results: Expression miR-6991-3p was markedly decreased in the MDSCs derived from spleen and further decreased in the MDSCs derived from the tumor tissue. MiR-6991-3p mimic transfection suppressed expansion and promoted apoptosis of MDSCs, accompanied by a significant decrease in the production of IL-6 and GM-CSF that are identified as stimulators in MDSC expansion. In contrast, miR-6991-3p inhibitor transfection displayed the opposite effect. miR-6991-3p bound with and negatively regulated expression of LGALS9, a newly identified immune checkpoint gene and activator of STAT3, suppressing production of multiple factors that were customarily used to characterize the activation of MDSCs. MiR-6991-3p-accommodated MDSCs displayed less suppression on T cells, while miR-6991-3p inhibitor enhanced the suppression of MDSCs on T cells. Conclusion: MiR-6991-3p is identified as a novel suppressor in the expansion and activation of myeloid-derived suppressor cells, which may be regarded as a promising target for modulating the function of MDSCs.

15.
Ann Surg Oncol ; 26(2): 635-643, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30374923

RESUMO

BACKGROUND: Tumor-infiltrating neutrophils (TINs) indicate poor prognosis for patients with pancreatic ductal adenocarcinoma (PDAC). Activated neutrophils can generate neutrophil extracellular traps (NETs). Little is known about the presence and prognostic significance of tumor-infiltrating NETs in PDAC. METHODS: This study enrolled 317 patients, in two independent sets (training and validation), who underwent curative pancreatectomy for PDAC in Shanghai Cancer Center. TINs and NETs were identified by immunohistochemical staining for CD15 and citrullinated histone H3, respectively. The relationship between clinicopathological features and outcomes was analyzed. Accuracy of prognostic prediction models was evaluated using concordance index (C-index) and Akaike information criterion (AIC). RESULTS: NETs were associated with OS (both, P < 0.001) and RFS (both, P < 0.001) in the training and validation sets. Tumor-infiltrating NETs predicted poor postsurgical survival of patients with PDAC. Moreover, multivariate analysis identified NETs and AJCC TNM stage as two independent prognostic factors for OS and RFS. Combination of NETs with the 8th edition TNM staging system (C-index, 0.6994 and 0.6669, respectively; AIC, 1067 and 1126, respectively) generated a novel model that improved the predictive accuracy for survival in both sets (C-index, 0.7254 and 0.7117, respectively; AIC, 1047 and 1102, respectively). The model combining presence of NETs with the 7th edition AJCC TNM staging system also had improved predictive accuracy. CONCLUSIONS: NETs were an independent prognostic factor in PDAC and incorporation of NETs along with the standard TNM stating system refined risk-stratification and predicted survival in PDAC with improved accuracy.


Assuntos
Carcinoma Ductal Pancreático/mortalidade , Armadilhas Extracelulares , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Taxa de Sobrevida
16.
Eur J Surg Oncol ; 45(5): 769-775, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30416079

RESUMO

INTRODUCTION: Arpin (Arp2/3 complex inhibitor), a novel protein found in 2013, plays a pivotal role in cell motility and migration. However, the prognostic value of Arpin in pancreatic ductal adenocarcinoma (PDAC) remains unknown. MATERIALS AND METHODS: We analyzed the gene expression of ARPIN using the GEO dataset (GSE71989) and validated the results by immunohistochemistry (IHC) and Western blot in our clinical database. Tissue microarray specimens from 214 patients who underwent curative pancreatectomy for PDAC were used. The tumors that expressed high and low levels of Arpin were compared with patient outcome using Kaplan-Meier curves and the multivariate Cox proportional hazard regression model. IHC was then used in 43 paired primary tumor tissues and metastasis tissues to detect the expression of Arpin. RESULTS: Arpin had low expression in the tumor tissue compared with the paracancerous tissue in PDAC. Patients with low intratumoral Arpin expression had worse overall survival (OS) and recurrence-free survival (RFS) than patients with high expression in the training set (p < 0.001, p < 0.001) and validation set (p < 0.001, p < 0.001). The multivariate analysis revealed that the 8th edition TNM stage and Arpin expression were independent prognostic factors associated with OS and RFS in the training and validation sets, respectively. Arpin had lower expression in the metastasis tissues than in the primary tumors of patients with PDAC (p = 0.048). CONCLUSION: The Arpin level is an independent prognostic factor that can be a potential predictor to aid in the management of PDAC.


Assuntos
Carcinoma Ductal Pancreático/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias Pancreáticas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Proteínas de Transporte/genética , China , Progressão da Doença , Regulação para Baixo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Análise Serial de Proteínas , Taxa de Sobrevida
17.
Angiogenesis ; 22(1): 15-36, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30168025

RESUMO

Pancreatic cancer is one of the most lethal malignancies worldwide. Although the standard of care in pancreatic cancer has improved, prognoses for patients remain poor with a 5-year survival rate of < 5%. Angiogenesis, namely, the formation of new blood vessels from pre-existing vessels, is an important event in tumor growth and hematogenous metastasis. It is a dynamic and complex process involving multiple mechanisms and is regulated by various molecules. Inhibition of angiogenesis has been an established therapeutic strategy for many solid tumors. However, clinical outcomes are far from satisfying for pancreatic cancer patients receiving anti-angiogenic therapies. In this review, we summarize the current status of angiogenesis in pancreatic cancer research and explore the reasons for the poor efficacy of anti-angiogenic therapies, aiming to identify some potential therapeutic targets that may enhance the effectiveness of anti-angiogenic treatments.

18.
Curr Med Chem ; 26(40): 7196-7211, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29651946

RESUMO

BACKGROUND: Awareness of the benefits of neoadjuvant therapy is increasing, but its use as an initial therapeutic option for patients with resectable pancreatic cancer remains controversial, especially for those patients without high-risk prognostic features. Even for patients with high-risk features who are candidates to receive neoadjuvant therapy, no standard regimen exists. METHODS: In this review, we examined available data on the neoadjuvant therapy in patients with resectable pancreatic cancer, including prospective studies, retrospective studies, and ongoing clinical trials, by searching PubMed/MEDLINE, ClinicalTrials.gov, Web of Science, and Cochrane Library. The characteristics and results of screened studies were described. RESULTS: Retrospective and prospective studies with reported results and ongoing randomized studies were included. For patients with resectable pancreatic cancer, neoadjuvant therapy provides benefits such as increased survival, decreased risk of comorbidities and mortality, and improved cost-effectiveness due to an increased completion rate of multimodal treatment. Highly active regimens such as FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin) or gemcitabine plus nab-paclitaxel are considered acceptable therapeutic regimens. Additionally, platinum-containing regimens other than FOLFIRINOX are acceptable for selected patients. Other therapies, such as chemoradiation treatment, immuno-oncology agents, and targeted therapies are being explored and the results are highly anticipated. CONCLUSION: This review highlights the benefits of neoadjuvant therapy for resectable pancreatic cancer. Some regimens are currently acceptable, but need more evidence from well-designed clinical trials or should be used after being carefully examined by a multidisciplinary team.


Assuntos
Terapia Neoadjuvante , Neoplasias Pancreáticas/terapia , Humanos
19.
World J Gastroenterol ; 24(43): 4893-4905, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30487699

RESUMO

AIM: To uncover the roles of tumor-promoting gene ZEB1 in aerobic glycolysis regulation and shed light on the underlying molecular mechanism. METHODS: Endogenous zinc finger E-box binding homeobox-1 (ZEB1) was silenced using a lentivirus-mediated method, and the impact of ZEB1 and methyl-CpG binding domain protein 1 (MBD1) on aerobic glycolysis was measured using seahorse cellular flux analyzers, reactive oxygen species quantification, and mitochondrial membrane potential measurement. The interaction between ZEB1 and MBD1 was assessed by co-immunoprecipitation and immunofluorescence assays. The impact of ZEB1 and MBD1 interaction on sirtuin 3 (SIRT3) expression was confirmed by quantitative polymerase chain reaction, western blotting, and dual-luciferase and chromatin-immunoprecipitation assays. RESULTS: ZEB1 was a positive regulator of aerobic glycolysis in pancreatic cancer. ZEB1 transcriptionally silenced expression of SIRT3, a mitochondrial-localized tumor suppressor, through interaction with MBD1. CONCLUSION: ZEB1 silenced SIRT3 expression via interaction with MBD1 to promote aerobic glycolysis in pancreatic cancer.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Glicólise/genética , Neoplasias Pancreáticas/genética , Sirtuína 3/genética , Fatores de Transcrição/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Mitocôndrias/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Sirtuína 3/metabolismo , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética
20.
J Cancer ; 9(18): 3417-3426, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30271504

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer. The 5-year survival rate for PDAC remains low because it is always diagnosed at an advanced stage and it is resistant to therapy. A biomarker, which could detect asymptomatic premalignant or early malignant tumors and predict the response to treatment, will benefit patients with PDAC. However, traditional biopsy has its limitations. There is an urgent need for a tumor biomarker that could easily and repeatedly sample and monitor, in real time, the progress of tumor development. Liquid biopsy could be a tool to assess potential biomarkers. In this review, we focused on the latest discoveries and advancements of liquid biopsy technology in pancreatic cancer research and demonstrated how this technology is being used in clinical applications.

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