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1.
Br J Cancer ; 116(8): 1012-1020, 2017 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-28278514

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease in terms of molecular carcinogenic pathways. Based on recent findings regarding the multiple serrated neoplasia pathway, we revised an eight-marker panel for a new CIMP classification system. METHODS: 1370 patients who received surgical resection for CRCs were classified into three CIMP subtypes (CIMP-N: 0-4 methylated markers, CIMP-P1: 5-6 methylated markers and CIMP-P2: 7-8 methylated markers). Our findings were validated in a separate set of high-risk stage II or stage III CRCs receiving adjuvant fluoropyrimidine plus oxaliplatin (n=950). RESULTS: A total of 1287/62/21 CRCs cases were classified as CIMP-N/CIMP-P1/CIMP-P2, respectively. CIMP-N showed male predominance, distal location, lower T, N category and devoid of BRAF mutation, microsatellite instability (MSI) and MLH1 methylation. CIMP-P1 showed female predominance, proximal location, advanced TNM stage, mild decrease of CK20 and CDX2 expression, mild increase of CK7 expression, BRAF mutation, MSI and MLH1 methylation. CIMP-P2 showed older age, female predominance, proximal location, advanced T category, markedly reduced CK20 and CDX2 expression, rare KRAS mutation, high frequency of CK7 expression, BRAF mutation, MSI and MLH1 methylation. CIMP-N showed better 5-year cancer-specific survival (CSS; HR=0.47; 95% CI: 0.28-0.78) in discovery set and better 5-year relapse-free survival (RFS; HR=0.50; 95% CI: 0.29-0.88) in validation set compared with CIMP-P1. CIMP-P2 showed marginally better 5-year CSS (HR=0.28, 95% CI: 0.07-1.22) in discovery set and marginally better 5-year RFS (HR=0.21, 95% CI: 0.05-0.92) in validation set compared with CIMP-P1. CONCLUSIONS: CIMP subtypes classified using our revised system showed different clinical outcomes, demonstrating the heterogeneity of multiple serrated precursors of CIMP-positive CRCs.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/classificação , Neoplasias Colorretais/patologia , Ilhas de CpG/genética , Metilação de DNA , Instabilidade de Microssatélites , Mutação/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Taxa de Sobrevida
2.
Mod Pathol ; 30(2): 267-277, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27713423

RESUMO

Acetyl-CoA synthetase-2 is an emerging key enzyme for cancer metabolism, which supplies acetyl-CoA for tumor cells by capturing acetate as a carbon source under stressed conditions. However, implications of acetyl-CoA synthetase-2 in colorectal carcinoma may differ from other malignancies, because normal colonocytes use short-chain fatty acids as an energy source, which are supplied by fermentation of the intestinal flora. Here we analyzed acetyl-CoA synthetase-2 mRNA expression by reverse-transcription quantitative PCR in paired normal mucosa and tumor tissues of 12 colorectal carcinomas, and subsequently evaluated acetyl-CoA synthetase-2 protein expression by immunohistochemistry in 157 premalignant colorectal lesions, including 60 conventional adenomas and 97 serrated polyps, 1,106 surgically resected primary colorectal carcinomas, and 23 metastatic colorectal carcinomas in the liver. In reverse-transcription quantitative PCR analysis, acetyl-CoA synthetase-2 mRNA expression was significantly decreased in tumor tissues compared with corresponding normal mucosa tissues. In acetyl-CoA synthetase-2 immunohistochemistry analysis, all 157 colorectal polyps showed moderate-to-strong expression of acetyl-CoA synthetase-2. However, cytoplasmic acetyl-CoA synthetase-2 expression was downregulated (acetyl-CoA synthetase-2 low expression) in 771 (69.7%) of 1,106 colorectal carcinomas and 21 (91.3%) of 23 metastatic lesions. The colorectal carcinomas with acetyl-CoA synthetase-2-low expression were significantly associated with advanced TNM stage, poor differentiation, and frequent tumor budding. Regarding the molecular aspect, acetyl-CoA synthetase-2-low expression exhibited a tendency of frequent KRT7 expression and decreased KRT20 and CDX2 expression. In survival analysis, acetyl-CoA synthetase-2-low expression was an independent prognostic factor for poor 5-year progression-free survival (hazard ratio, 1.39; 95% confidence interval, 1.08-1.79; P=0.01). In conclusion, these findings suggest that downregulation of acetyl-CoA synthetase-2 expression is a metabolic hallmark of tumor progression and aggressive behavior in colorectal carcinoma.


Assuntos
Acetato-CoA Ligase/metabolismo , Adenoma/metabolismo , Polipose Adenomatosa do Colo/metabolismo , Carcinoma/metabolismo , Neoplasias Colorretais/metabolismo , Regulação para Baixo , Invasividade Neoplásica/patologia , Acetato-CoA Ligase/genética , Adenoma/genética , Adenoma/mortalidade , Adenoma/patologia , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/mortalidade , Polipose Adenomatosa do Colo/patologia , Idoso , Carcinoma/genética , Carcinoma/mortalidade , Carcinoma/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Prognóstico
3.
Chemosphere ; 361: 142570, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38852636

RESUMO

Various contaminants of emerging concern (CECs) including pharmaceuticals and personal care products (PPCPs) have been known to threaten the aquatic ecosystem and human health even at low levels in surface water. Among them, the wide variety use of parabens as preservatives may pose potential threat to human because parabens may present estrogenic activity. Various advanced oxidation processes have been attempted to reduce parabens, but challenges using cold plasma (CP) are very rare. CP is worth paying attention to in reducing parabens because it has the advantage of generating radical ions, including reactive oxygen/nitrogen species and various ions. Accordingly, this study demonstrates how CP can be utilized and how CP competes with other advanced oxidation processes in energy requirements. Quantified ethyl-, propyl-, and butyl-paraben indicate that CP can effectively degrade them up to 99.1% within 3 h. Regression reveals that the kinetic coefficients of degradation can be increased to as high as 0.0328 min-1, comparable to other advanced oxidation processes. Many by-products generated from the oxidation of parabens provide evidence of the potential degradation pathway through CP treatment. In addition, we found that the electrical energy consumption per order of CP (39-95 kWh/m3/order) is superior to other advanced oxidation processes (69∼31,716 kWh/m3/order). Overall, these results suggest that CP may be a viable option to prevent adverse health-related consequences associated with parabens in receiving water.


Assuntos
Oxirredução , Parabenos , Poluentes Químicos da Água , Parabenos/química , Poluentes Químicos da Água/química , Gases em Plasma/química , Cinética , Conservantes Farmacêuticos/química
5.
Neurochem Res ; 38(12): 2640-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24146201

RESUMO

Glucose is a main energy source for normal brain functions. Glucokinase (GK) plays an important role in glucose metabolism as a glucose sensor, and GK activity is modulated by glucokinase regulatory protein (GKRP). In this study, we examined the changes of GK and GKRP immunoreactivities in the gerbil hippocampus after 5 min of transient global cerebral ischemia. In the sham-operated-group, GK and GKRP immunoreactivities were easily detected in the pyramidal neurons of the stratum pyramidale of the hippocampus. GK and GKRP immunoreactivities in the pyramidal neurons were distinctively decreased in the hippocampal CA1 region (CA), not CA2/3, 3 days after ischemia-reperfusion (I-R). Five days after I-R, GK and GKRP immunoreactivities were hardly detected in the CA1, not CA2/3, pyramidal neurons; however, at this point in time, GK and GKRP immunoreactivities were newly expressed in astrocytes, not microglia, in the ischemic CA1. In brief, GK and GKRP immunoreactivities are changed in pyramidal neurons and newly expressed in astrocytes in the ischemic CA1 after transient cerebral ischemia. These indicate that changes of GK and GKRP expression may be related to the ischemia-induced neuronal damage/death.


Assuntos
Proteínas de Transporte/metabolismo , Glucoquinase/metabolismo , Hipocampo/metabolismo , Ataque Isquêmico Transitório/metabolismo , Animais , Western Blotting , Imunofluorescência , Gerbillinae , Hipocampo/enzimologia , Ataque Isquêmico Transitório/enzimologia , Masculino
6.
J Korean Med Sci ; 28(6): 962-4, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23772167

RESUMO

Neurogenic pulmonary edema (NPE) leading to cardiopulmonary dysfunction is a potentially life-threatening complication in patients with central nervous system lesions. This case report describes a 28-yr woman with life-threatening fulminant NPE, which was refractory to conventional respiratory treatment, following the rupture of an aneurysm. She was treated successfully with extracorporeal membrane oxygenation (ECMO), although ECMO therapy is generally contraindicated in neurological injuries such as brain trauma and diseases that are likely to require surgical intervention. The success of this treatment suggests that ECMO therapy should not be withheld from patients with life-threatening fulminant NPE after subarachnoid hemorrhage.


Assuntos
Aneurisma Intracraniano/diagnóstico , Edema Pulmonar/diagnóstico , Adulto , Encéfalo/diagnóstico por imagem , Craniectomia Descompressiva , Oxigenação por Membrana Extracorpórea , Feminino , Humanos , Aneurisma Intracraniano/complicações , Edema Pulmonar/etiologia , Edema Pulmonar/terapia , Hemorragia Subaracnóidea/etiologia , Tomografia Computadorizada por Raios X
7.
Cell Mol Neurobiol ; 32(7): 1209-21, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22814803

RESUMO

Alpha-lipoic acid (ALA), a natural antioxidant, is widely used for the treatment of some diseases including diabetes, and decursinol (DA), a constituent of root of Angelica gigas Nakai, has some pharmacological activities including anti-inflammatory function. In this study, we synthesized a novel synthetic alpha-lipoic acid-decursinol (ALA-DA) hybrid compound, and compared neuroprotective effects of ALA, DA or ALA-DA against ischemic damage in the gerbil hippocampal CA1 region induced by 5 min of transient cerebral ischemia. In the 10 and 20 mg/kg ALA-, DA- and 10 mg/kg ALA-DA-pre-treated-ischemia-groups, there were no neuroprotective effects against ischemic damage 4 days after ischemic injury. However, 20 mg/kg ALA-DA pre-treatment protected pyramidal neurons from ischemic damage in the CA1 region. In addition, 20 mg/kg ALA-DA pre-treatment markedly decreased the activation of astrocytes and microglia in the CA1 region 4 days after ischemic injury. On the other hand, post-treatment with the same dosages of them did not show any neuroprotective effect against ischemic damage. In brief, these findings indicate that pre-treatment with ALA-DA, not ALA or DA alone, can protect neurons from ischemic damage in the hippocampus induced by transient cerebral ischemia via the decrease of glial activation.


Assuntos
Modelos Animais de Doenças , Ataque Isquêmico Transitório/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Ácido Tióctico/uso terapêutico , Animais , Gerbillinae , Ataque Isquêmico Transitório/metabolismo , Ataque Isquêmico Transitório/patologia , Masculino , Fármacos Neuroprotetores/síntese química , Ácido Tióctico/síntese química
8.
Neurochem Res ; 37(5): 1019-30, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22246227

RESUMO

In the present study, we compared the immunoreactivities and levels of Trx/prx redox system, thioredoxin 2 (Trx2), thioredoxin reductase 2 (TrxR2) and peroxiredoxin 3 (Prx3), as well as neuronal death in the hippocampal CA1 region between the adult and young gerbil after 5 min of transient cerebral ischemia. At 4 days post-ischemia, pyramidal neurons (about 90%) in the adult stratum pyramidale of the CA1 region showed "delayed neuronal death (DND)"; however, at this time point, few pyramidal neurons showed DND in the young stratum pyramidale. At 7 days post-ischemia, about 56% of pyramidal neurons showed DND in the young stratum pyramidale. The immunoreactivities of all the antioxidants in the young sham-group were similar to those in the adult sham-group. At 4 days post-ischemia, the immunoreactivity of TrxR2, not Trx2 and Prx3 in the adult ischemia-group was dramatically decreased in CA1 pyramidal neurons. At this time point, the immunoreactivities of all the antioxidants in the young ischemia-group were apparently increased compared to the adult ischemia-group. From 7 days pots-ischemia, non-pyramidal cells showed the immunoreactivities of all the antioxidants in the ischemic CA1 region; however, in the young ischemia-groups, the immunoreactivities were much lower than those in the adult ischemia-groups. In brief, our results showed that the immunoreactivities of Trx2, TrxR2 and Prx3 were dramatically increased in CA1 pyramidal neurons of the young ischemia-groups at 4 days post-ischemia compared to those in the adult ischemia-groups induced by transient cerebral ischemia.


Assuntos
Isquemia Encefálica/metabolismo , Hipocampo/metabolismo , Peroxirredoxina III/metabolismo , Tiorredoxinas/metabolismo , Fatores Etários , Animais , Western Blotting , Isquemia Encefálica/patologia , Gerbillinae , Hipocampo/patologia , Imuno-Histoquímica , Masculino , Oxirredução
9.
Phys Chem Chem Phys ; 14(48): 16552-7, 2012 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-22772941

RESUMO

As a first step towards a microscopic understanding of single-Pt atom-dispersed catalysts on non-conventional TiN supports, we present density-functional theory (DFT) calculations to investigate the adsorption properties of Pt atoms on the pristine TiN(100) surface, as well as the dominant influence of surface defects on the thermodynamic stability of platinized TiN. Optimized atomic geometries, energetics, and analysis of the electronic structure of the Pt/TiN system are reported for various surface coverages of Pt. We find that atomic Pt does not bind preferably to the clean TiN surface, but under typical PEM fuel cell operating conditions, i.e. strongly oxidizing conditions, TiN surface vacancies play a crucial role in anchoring the Pt atom for its catalytic function. Whilst considering the energetic stability of the Pt/TiN structures under varying N conditions, embedding Pt at the surface N-vacancy site is found to be the most favorable under N-lean conditions. Thus, the system of embedding Pt at the surface N-vacancy sites on TiN(100) surfaces could be promising catalysts for PEM fuel cells.

10.
Ear Nose Throat J ; : 1455613221098787, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35487204

RESUMO

Laryngopharyngeal or cervical pain following ingestion of foreign bodies is one of the most frequently encountered emergencies in otolaryngologic practice. Although most of these foreign bodies can be easily removed under laryngoscopic examination without any complications, surgical removal may be required when foreign bodies migrate extraluminally. This report describes two rare cases of ingested fishbones that had migrated, one each to the thyroid gland and submandibular gland. Extraluminal migration fishbones should always be considered in otolaryngologic clinics.

11.
J Electron Microsc (Tokyo) ; 60(2): 143-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21393371

RESUMO

In this study, microstructures of Cu powders coated with octanethiol were analyzed using (scanning) transmission electron microscopy. Moreover, aging process of the octanethiol-coated layer as time passes by was analyzed using the electron energy loss spectroscopy technique. The octanethiol layer coated on the surface of Cu powders was kept until it was exposed to air for around 30 days. As days passes by, the coating layer had been decomposed and then a Cu(2)O layer was formed on the surface of powders.

12.
Knee Surg Relat Res ; 32(1): 45, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867827

RESUMO

SUBJECT: This study compared clinical outcomes and second-look arthroscopic evaluations between anterior cruciate ligament (ACL) anteromedial (AM) bundle augmentation and single-bundle ACL reconstruction. PURPOSE: We compared the clinical results and the second-look arthroscopic findings between (1) single-bundle ACL reconstruction in complete rupture and (2) ACL AM bundle augmentation in isolated AM bundle rupture. MATERIALS AND METHODS: Two groups of patients underwent ACL surgery from January 2013 to December 2018. Group 1, who had 64 cases of single-bundle ACL reconstruction with second-look arthroscopy, and Group 2, who had 21 cases of AM bundle augmentation of ACL with second-look arthroscopy, were targeted. We evaluated and compared the clinical results (Lysholm score, Tegner activity score, Lachman test, and pivot-shift test) and synovialization at second-look arthroscopy before the operation and in the final follow-up period, between Group 1 and Group 2. RESULTS: The Lysholm score (p = 0.96) and Tegner activity score (p = 0.351) at final follow-up (mean 27.1 months) were 78.3 and 7.2 in Group 1 and 89.1 and 8.1 in Group 2, respectively. The Lachman test (p = 0.074) and pivot-shift test (p = 0.031) results at final follow-up were improved; however, there was no statistical significance. Second-look arthroscopy showed that percentages of synovialization area of grafted tendon at mean 15.6 months follow-up were 61.4% and 93.1% in Group 1 and Group 2, respectively (p = 0.008). The synovial coverage in Group 2 was higher than in Group 1. CONCLUSION: The AM bundle augmentation for ACL injury in which the posterolateral bundle was preserved showed better clinical scores and synovial coverage than single-bundle ACL reconstruction for complete ACL rupture. LEVEL OF EVIDENCE: The level of evidence is Level III, retrospective with case series.

13.
Materials (Basel) ; 13(13)2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32610552

RESUMO

A real-time, accurate, and reliable process monitoring is a basic and crucial enabler of intelligent manufacturing operation and digital twin applications. In this study, we represent a novel vibration measurement method for workpiece during the milling process using a low-cost nanoparticle vibration sensor. We directly printed the vibration sensor based on silver nanoparticles positioned onto a polyimide substrate using an aerodynamically-focused nanomaterials printing system, which is a direct printing technique for inorganic nanomaterials positioned onto a flexible substrate. Since it does not require any post-process such as chemical etching and heat treatment, a highly sensitive vibration sensor composed of a microscale porous structure was fabricated at a cost of several cents each. Furthermore, accurate and reliable vibration data was obtained by simple and direct attachment to a workpiece. In this study, we discussed the performance of vibration measurement of a fabricated sensor in comparison to a commercial vibration sensor. Using frequency and power spectrum analysis of obtained data, we directly measured the vibration of workpiece during the milling process, according to a process parameter. Lastly, we applied a fabricated sensor for the digital twins of turbine blade manufacturing in which vibration greatly affects the quality of the product to predict the process defects in real-time.

14.
Emerg Med Int ; 2018: 8701957, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30245884

RESUMO

Due to an increase in traffic collisions, the demand for prehospital medical services is on the rise, even in low-resource countries where emergency ambulance services have not been previously provided. To build a sustainable and continuous prehospital ambulance operation model, it is necessary to consider the medical system and economic conditions of the corresponding country. In an attempt to construct a prehospital ambulance operation model that ensures continuous operation, a pilot "emergency patient transporting service from field to hospital" operation was established for approximately three months in Kinshasa, the capital of the DR Congo. To construct a continuously operating model even after the pilot operation, willingness to pay (WTP) by type of emergency medical and transport service was investigated by implementing the contingent valuation method (CVM). Using CVM, the WTP for prehospital emergency services targeting ambulance services personnel, patients, policemen, and hospital staff participating in the pilot operation was calculated. The results of the pilot operation revealed that there were a total of 212 patients with a mean patient number of 2.4 per day. A total of 155 patients used the services for hospital transport, while 121 patients used the services for traffic collisions. Traffic collisions were the category in which ambulance services were most frequently needed (66.2%). Pay services were most frequently utilized in the home-visit services category (40.9%). Based on these results, eight independently operated ambulance operation models and sixteen models that utilize hospital medical personnel and policemen already belonging to existing institutions were proposed. In an effort to implement emergency medical ambulance services in the DR Congo, medical staff receiving pay for performance (incentive pay) should be deployed in the field and on call. Accordingly, with respect to sustainable development goals, various pay-for-service models should be used.

15.
J Microbiol Biotechnol ; 27(11): 2010-2018, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-28870010

RESUMO

Mixotrophic microalgal growth gives a great premise for wastewater treatment based on photoautotrophic nutrient utilization and heterotrophic organic removal while producing renewable biomass. There remains a need for a control strategy to enrich them in a photobioreactor. This study performed a series of batch experiments using a mixotroph, Chlorella sorokiniana, to characterize optimal guidelines of mixotrophic growth based on a statistical design of the experiment. Using a central composite design, this study evaluated how temperature and light irradiance are associated with CO2 capture and organic carbon respiration through biomass production and ammonia removal kinetics. By conducting regressions on the experimental data, response surfaces were created to suggest proper ranges of temperature and light irradiance that mixotrophs can beneficially use as two types of energy sources. The results identified that efficient mixotrophic metabolism of Chlorella sorokiniana for organics and inorganics occurs at the temperature of 30-40°C and diurnal light condition of 150-200 µmol E·m2·s-1. The optimal specific growth rate and ammonia removal rate were recorded as 0.51/d and 0.56/h on average, respectively, and the confirmation test verified that the organic removal rate was 105 mg COD·l-1·d-1. These results support the development of a viable option for sustainable treatment and effluent quality management of problematic livestock wastewater.


Assuntos
Chlorella/crescimento & desenvolvimento , Chlorella/metabolismo , Processos Heterotróficos/fisiologia , Luz , Gado , Processos Fototróficos/fisiologia , Temperatura , Águas Residuárias/microbiologia , Amônia/metabolismo , Análise de Variância , Animais , Biodegradação Ambiental , Análise da Demanda Biológica de Oxigênio , Biomassa , Carbono/metabolismo , Dióxido de Carbono/metabolismo , Técnicas de Cultura de Células , Chlorella/efeitos da radiação , Meios de Cultura/química , Cinética , Nitrogênio/metabolismo , Compostos Orgânicos , Fósforo/metabolismo , Fotobiorreatores , Análise de Regressão , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Purificação da Água
16.
Hum Pathol ; 67: 109-118, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28811251

RESUMO

Deletion of the HSP110 T17 mononucleotide repeat has recently been identified as a prognostic marker that is correlated with wild-type HSP110 (HSP110wt) expression in microsatellite instability-high (MSI-H) colorectal cancers. The aim of this study was to assess the correlation between deletion of the HSP110 T17 repeat and expression of HSP110wt using DNA testing and immunohistochemistry and to determine the prognostic implications of HSP110 T17 deletion in MSI-H advanced gastric cancers (GCs). The status of HSP110wt expression was evaluated by immunohistochemistry using an HSP110wt-specific antibody in 142 MSI-H advanced GCs. The size of the HSP110 T17 repeat deletion was analyzed in 96 MSI-H advanced GCs; deletions were divided into small (0-2base pairs) and large deletions (3-5base pairs). Low and high expressions of HSP110wt were detected in 38 (26.8%) and 104 (73.2%) of the 142 cases, respectively. The HSP110 T17 deletion was observed in 45 (46.9%) of the 96 MSI-H GC samples. Tumors with high expression of HSP110wt showed a tendency to have small or no deletion of HSP110 T17. In Kaplan-Meier survival analysis, tumors with a large HSP110 T17 deletion were associated with favorable overall survival and disease-free survival compared with those with small/no deletion of HSP110 T17. However, HSP110 T17 deletion size was not an independent prognostic factor in multivariate analysis. In summary, deletion of the HSP110 T17 repeat was frequently observed in MSI-H GCs, and HSP110 T17 deletion size was inversely correlated with HSP110wt expression status. Large HSP110 T17 was not a prognostic indicator in MSI-H GCs.


Assuntos
Biomarcadores Tumorais/genética , Proteínas de Choque Térmico HSP110/genética , Instabilidade de Microssatélites , Repetições de Microssatélites , Deleção de Sequência , Neoplasias Gástricas/genética , Idoso , Biomarcadores Tumorais/análise , Distribuição de Qui-Quadrado , Reparo de Erro de Pareamento de DNA , Análise Mutacional de DNA , Progressão da Doença , Intervalo Livre de Doença , Feminino , Predisposição Genética para Doença , Proteínas de Choque Térmico HSP110/análise , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fenótipo , Fatores de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Fatores de Tempo , Análise Serial de Tecidos , Resultado do Tratamento
17.
J Antibiot (Tokyo) ; 70(11): 1065-1069, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28874849

RESUMO

In many pathogenic Gram-negative bacteria, such as Salmonella, Escherichia coli, Yersinia and Chlamydia spp., which cause diseases in humans, the type III secretion system (TTSS) is an important virulence factor that translocates effector proteins into the cytosol of host cells. Thus, the TTSS is a good target for antibacterial agents. Here we used a hemolysis assay to search for TTSS inhibitors and found that a compound from Magnolia obovata called obovatol blocks the TTSS of Salmonella. Obovatol showed potent inhibitory activity (IC50=19.8 µM) against the TTSS-related hemolysis of Salmonella, which was not due to a reduction of bacterial growth. Instead, the compound inhibited bacterial motility, TTSS-related mRNA expression and effector protein secretion. These data demonstrate the inhibitory effect of obovatol on the Salmonella TTSS and suggest that it could be useful for the prevention and supplementary treatment of bacterial infections.


Assuntos
Compostos de Bifenilo/farmacologia , Magnolia/química , Éteres Fenílicos/farmacologia , Salmonella/patogenicidade , Sistemas de Secreção Tipo III/efeitos dos fármacos , Antibacterianos/administração & dosagem , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/isolamento & purificação , Hemólise/efeitos dos fármacos , Concentração Inibidora 50 , Éteres Fenílicos/administração & dosagem , Éteres Fenílicos/isolamento & purificação
18.
APMIS ; 125(12): 1076-1083, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28971530

RESUMO

The aim of this study is to establish heat shock protein 110 (HSP110) as a prognostic biomarker of colorectal carcinomas (CRCs) with microsatellite instability-high (MSI-H) by considering the intratumoral heterogeneity of HSP110 expression. We performed whole-section immunohistochemistry (IHC) for wild-type HSP110 (HSP110wt) in 164 MSI-H CRCs. The intensity of the HSP110wt expression in tumor cells was semiquantitatively scored (0/1/2/3), and the HSP110wt expression status of each tumor was classified as low or high using the following four scoring criteria: H-score, dominant intensity score, lowest intensity score, and highest intensity score. Among the four criteria, only the dominant intensity score-based dichotomous classification of HSP110wt expression was significantly associated with a difference in disease-free survival (log-rank p = 0.035) in 164 MSI-H CRCs. The HSP110wt-low MSI-H CRCs were significantly correlated with larger deletions in the HSP110 T17 mononucleotide repeat (≥4 bp; p < 0.001). In conclusion, the dominant intensity score-based assessment of HSP110wt IHC can be a simple and useful method for the prognostic stratification of MSI-H CRCs. It is expected that HSP110wt IHC may be used to identify a subgroup of MSI-H CRCs with poor prognosis and/or candidates for further treatment, such as immunotherapy using immune checkpoint inhibitors in MSI-H CRCs.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Proteínas de Choque Térmico HSP110/metabolismo , Instabilidade de Microssatélites , Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Expressão Gênica , Proteínas de Choque Térmico HSP110/genética , Humanos , Imuno-Histoquímica , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Prognóstico , Deleção de Sequência , Análise Serial de Tecidos
19.
Clin Epigenetics ; 8: 36, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27051466

RESUMO

BACKGROUND: Low methylation status of LINE-1 in tumors is associated with poor survival in patients with colon cancer. Eastern Cooperative Oncology Group performance status (ECOG-PS) is a method to assess the functional status of a patient. We retrospectively evaluated the relationship between ECOG-PS and LINE-1 methylation in colorectal cancers (CRCs) and their prognostic impact in CRC or colon cancer patients receiving adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX). RESULTS: LINE-1 methylation and microsatellite instability were analyzed in stage III or high-risk stage II CRCs (n = 336). LINE-1 methylation levels were correlated with clinicopathological features, including PS and recurrence-free survival (RFS). The association between the tumoral LINE-1 methylation level and PS was observed (OR = 2.56, P < 0.001). Differences in LINE-1 methylation levels in cancer tissue between the PS 0 and 1 groups were significant in patients older than 60 years (P = 0.001), the overweight body mass index group (P = 0.005), and the stage III disease group (P = 0.008). Prognostic significances of LINE-1 methylation status or combined PS and LINE-1 methylation statuses were identified in stage III colon cancers, not in stage III and high-risk stage II CRCs. Low LINE-1 methylation status was closely associated with a shorter RFS time. The difference between PS(0)/LINE-1(high) and PS(≥1)/LINE-1(low) was significant, which suggests that colon cancer patients with concurrent PS(≥1)/LINE-1 (low) have a higher recurrence rate. CONCLUSIONS: PS was associated with LINE-1 methylation in CRC tissue. LINE-1 methylation was associated with RFS in stage III colon cancer patients who were treated with adjuvant FOLFOX chemotherapy. Combined PS and LINE-1 methylation status might serve as a useful predictor of cancer recurrence.


Assuntos
Neoplasias do Colo/patologia , Metilação de DNA , Elementos Nucleotídeos Longos e Dispersos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/uso terapêutico , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
20.
Resuscitation ; 99: 50-5, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26690647

RESUMO

AIM: The grey-to-white matter ratio (GWR) is a reliable predictor of the neurological outcome of out-of-hospital cardiac arrest (OHCA). However, the reliability in patients receiving extracorporeal membrane oxygenation-assisted cardiopulmonary resuscitation (ECPR) remains unknown. We evaluated the utility of the GWR in predicting neurological outcomes in ECPR-treated patients. METHODS: This single-centre retrospective study was conducted from July 2009 to January 2014. Patients who received ECPR for OHCA were classified into two groups: Cerebral performance category(CPC) 1-2 was defined as good, CPC 3-5 as poor outcome. Four GWR (GWR-AV[average], GWR-CO[cortex], GWR-BG[basal ganglia], and GWR-SI [simplified])were evaluated and compared between the groups. RESULTS: Of 38 patients who received ECPR for OHCA, 30 patients were enrolled. Five (16.7%) had a good outcome and 25(83.3%) a poor outcome. All GWR were significantly higher in the good outcome group than in the poor outcome group. ROC curve analysis produced the following areas under the curve: GWR-AV=0.920 (95% CI 0.761 to 0.987), GWR-BG=0.872 (95%CI 0.699 to 0.965), GWR-CO=0.952 (95% CI 0.806 to 0.997), and GWR-SI=0.848(95% CI 0.670 to 0.962). The cut-off value with 100% specificity for the prediction of the poor outcome was 1.23 for GWR-AV (sensitivity: 76%), 1.24 for GWR-BG (sensitivity: 88.0%), 1.22 for GWR-CO (sensitivity: 64%), and 1.21 for GWR-SI (sensitivity: 76%). CONCLUSIONS: In ECPR, GWR of patients with poor outcome was significantly lower than that of patients with good outcome.


Assuntos
Oxigenação por Membrana Extracorpórea , Substância Cinzenta/diagnóstico por imagem , Parada Cardíaca Extra-Hospitalar/terapia , Tomografia Computadorizada por Raios X , Substância Branca/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
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