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1.
Am J Gastroenterol ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38546128

RESUMO

INTRODUCTION: We sought to determine the yield of somatic mutational analysis from endoscopic ultrasound (EUS)-guided biopsies of pancreatic adenocarcinoma compared with that of surgical resection and to assess the impact of these results on oncologic treatment. METHODS: We determined the yield of EUS sampling and surgical resection. We evaluated the potential impact of mutational analysis by identifying actionable mutations and its direct impact by reviewing actual treatment decisions. RESULTS: Yield of EUS sampling was 89.5%, comparable with the 95.8% yield of surgical resection. More than a quarter in the EUS cohort carried actionable mutations, and of these, more than 1 in 6 had treatment impacted by mutational analysis. DISCUSSION: EUS sampling is nearly always adequate for somatic testing and may have substantial potential and real impact on treatment decisions.

2.
Gastric Cancer ; 27(3): 622-634, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38502275

RESUMO

BACKGROUND: Fluorescent lymphography (FL) using indocyanine green (ICG) allows for the visualization of all draining lymph nodes (LNs), thereby increasing LN retrieval. However, no studies have assessed the efficacy of FL in high body mass index (BMI) gastric cancer patients, even as LN yield decreases with increasing BMI in gastrectomy. This study aimed to investigate the influence of FL on LN retrieval in high BMI gastric cancer patients. METHODS: Gastric cancer patients who underwent laparoscopic or robotic gastrectomies from 2013 to 2021 were included. Patients were classified into two groups, with FL (FL group) or without FL (non-FL group). The effect of FL on LN retrieval was assessed by BMI. Inverse probability of treatment weighting (IPTW) was used to ensure comparability between groups. RESULTS: Retrieved LN number decreased as BMI increased regardless of FL application (P < 0.001). According to the IPTW analysis, the mean retrieved LN number was significantly higher in the FL group (48.4 ± 18.5) than in the non-FL group (39.8 ± 16.3, P < 0.001), irrespective of BMI. The FL group exhibited a significantly higher proportion of patients with 16 or more LNs (99.5%) than the non-FL group (98.1%, P < 0.001). The FL group also had a significantly higher proportion of patients with 30 or more LNs (86.6%) than the non-FL group (72.2%, P < 0.001). In both the normal and high-BMI patients, the FL group had a significantly larger percentage of patients with a higher nodal classification than the non-FL group. CONCLUSION: FL resulted in more LN retrieval, even in high BMI patients. FL ensures accurate staging by maintaining the appropriate retrieved LN number in high BMI gastric cancer patients.


Assuntos
Linfografia , Neoplasias Gástricas , Humanos , Linfografia/métodos , Excisão de Linfonodo/métodos , Índice de Massa Corporal , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologia , Corantes , Gastrectomia/métodos , Estudos Retrospectivos
3.
Gastric Cancer ; 27(1): 176-186, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37872358

RESUMO

BACKGROUND: Previous studies have focused on the non-inferiority of RPG compared with conventional port gastrectomy (CPG); however, we assumed that some candidates might derive more significant benefit from RPG over CPG. METHODS: We retrospectively analyzed the clinicopathological and perioperative parameters of 1442 patients with gastric cancer treated by gastrectomy between 2009 and 2022. The C-reactive protein level on postoperative day 3 (CRPD3) was used as a surrogate parameter for surgical trauma. Patients were grouped according to the extent of gastrectomy [subtotal gastrectomy (STG) or total gastrectomy (TG)] and lymph node dissection (D1+ or D2). The degree of surgical trauma, bowel recovery, and hospital stay between RPG and CPG was compared among those patient groups. RESULTS: Of 1442 patients, 889, 354, 129, and 70 were grouped as STGD1+, STGD2, TGD1+, and TGD2, respectively. Compared with CPG, RPG significantly decreased CRPD3 only among patients in the STGD1+ group (CPG: n = 653, 84.49 mg/L, 95% CI 80.53-88.45 vs. RPG: n = 236, 70.01 mg/L, 95% CI 63.92-76.09, P < 0.001). In addition, the RPG method significantly shortens bowel recovery and hospital stay in the STGD1+ (P < 0.001 and P < 0.001), STGD2 (P < 0.001 and P < 0.001), and TGD1+ (P = 0.026 and P = 0.007), respectively. No difference was observed in the TGD2 group (P = 0.313 and P = 0.740). CONCLUSIONS: The best candidates for RPG are patients who undergo STGD1+, followed by STGD2 and TG D1+, considering the reduction in CRPD3, bowel recovery, and hospital stay.


Assuntos
Laparoscopia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Estudos Retrospectivos , Laparoscopia/métodos , Excisão de Linfonodo/métodos , Gastrectomia/métodos , Resultado do Tratamento
4.
Biochem Biophys Res Commun ; 552: 44-51, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33743348

RESUMO

Hepatocellular carcinoma (HCC) is the fifth common types of cancer with poor prognosis in the world. Honokiol (HNK), a natural biphenyl compound derived from the magnolia plant, has been reported to exert anticancer effects, but its mechanism has not been elucidated exactly. In the present study, HNK treatment significantly suppressed the migration ability of HepG2 and Hep3B human hepatocellular carcinoma. The treatment reduced the expression levels of the genes associated with cell migration, such as S100A4, MMP-2, MMP-9 and Vimentin. Interestingly, treatment with HNK significantly reduced the expression level of Cyclophilin B (CypB) which stimulates cancer cell migration. However, overexpressed CypB abolished HNK-mediated suppression of cell migration, and reversed the apoptotic effects of HNK. Altogether, we concluded that the suppression of migration activities by HNK was through down-regulated CypB in HCC. These finding suggest that HNK may be a promising candidate for HCC treatment via regulation of CypB.


Assuntos
Compostos de Bifenilo/farmacologia , Carcinoma Hepatocelular/genética , Movimento Celular/efeitos dos fármacos , Ciclofilinas/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Lignanas/farmacologia , Neoplasias Hepáticas/genética , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Ciclofilinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
5.
J Cell Physiol ; 234(7): 10345-10359, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30387140

RESUMO

LL-37, the only known human cathelicidin which is encoded by the human antimicrobial peptide (CAMP) gene, plays a critical role in protection against bacterial infection. We previously demonstrated that cathelicidin is induced by 1,25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ) in human airway epithelial cells with a resultant increase in bactericidal activity. In this study we identify key factors that co-operate with 1,25(OH) 2 D 3 in the regulation of CAMP. Our results show for the first time that PU.1, the myeloid transcription factor (which has also been identified in lung epithelial cells), co-operates with the vitamin D receptor and CCAAT/enhancer binding protein α (CEBPα) to enhance the induction of CAMP in lung epithelial cells. Our findings also indicate that enhancement of 1,25(OH) 2 D 3 regulation of CAMP by histone deacetylase inhibitors involves co-operation between acetylation and chromatin remodeling through Brahma-related gene 1 (BRG1; a component of the SWItch/sucrose nonfermentable [SWI/SNF] complex). BRG1 can be an activator or repressor depending on BRG1-associated factors. Protein arginine methyltransferase 5 (PRMT5), a methlytransferase which interacts with BRG1, represses 1,25(OH) 2 D 3 induced CAMP in part through dimethylation of H4R3. Our findings identify key mediators involved in the regulation of the CAMP gene in lung epithelial cells and suggest new approaches for therapeutic manipulation of gene expression to increase the antibacterial capability of the airway.


Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Proteínas Estimuladoras de Ligação a CCAAT/genética , Epigênese Genética/genética , Proteínas Proto-Oncogênicas/genética , Transativadores/genética , Vitamina D/análogos & derivados , Acetilação , Montagem e Desmontagem da Cromatina/genética , Células Epiteliais , Regulação da Expressão Gênica/genética , Células HEK293 , Humanos , Pulmão , Receptores de Calcitriol/genética , Fatores de Transcrição/genética , Transcrição Gênica/genética , Vitamina D/genética , Catelicidinas
6.
BMC Anesthesiol ; 17(1): 138, 2017 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-29020926

RESUMO

BACKGROUND: Pediatric MRI sedation performed by a variety of specialists such as sedationists and anesthesiologists commonly uses propofol, which has similar effects to an ideal sedative agent for maintaining deep sedation. However, when propofol is used, adverse airway events are relatively more common than when using other sedative agents. The concomitant administration of midazolam and propofol can reduce the dose of propofol needed for adequate sedation and might also reduce the frequency of airway obstruction without affecting the patient's recovery profile. METHODS: We reviewed the our hospital records of all pediatric MRI sedation patients aged 3 to 16 years who were sedated with either propofol alone or propofol with midazolam between December 2013 and June 2016. RESULTS: Eight hundred ninety-seven pediatric MRI sedation patients were included (n = 897). The frequency of airway intervention was 25/356 (7.0%) in Group P and 15/541 (2.8%) in Group PM (difference in proportions: 4.2%; 95% CI: 1.4-7.6%; p = 0.002). The mean (SD) time to awake was longer in Group PM compared to Group P [21.2 (5.6) minutes vs. 23.0 (7.1) minutes; mean difference, 1.8 min; 95% CI, 0.9-2.9; p < 0.001]. The mean (SD) time to discharge was longer in Group PM compared to Group P [34.5 (6.9) minutes vs. 38.6 (9.4) minutes; mean difference, 4.0 min; 95% CI, 3.0-5.1; p < 0.001]. CONCLUSIONS: The administration of a small dose of midazolam during pediatric MRI sedation using propofol can reduce the frequency of airway complications without prolonging the clinically significant recovery profile.


Assuntos
Hipnóticos e Sedativos/administração & dosagem , Complicações Intraoperatórias/prevenção & controle , Imageamento por Ressonância Magnética/métodos , Midazolam/administração & dosagem , Propofol/administração & dosagem , Adolescente , Período de Recuperação da Anestesia , Criança , Pré-Escolar , Estudos de Coortes , Quimioterapia Combinada , Feminino , Humanos , Hipnóticos e Sedativos/efeitos adversos , Complicações Intraoperatórias/induzido quimicamente , Masculino , Midazolam/efeitos adversos , Propofol/efeitos adversos , Estudos Retrospectivos
7.
Biochem Biophys Res Commun ; 479(3): 434-439, 2016 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-27641665

RESUMO

Amyotrophic lateral sclerosis (ALS) is a degenerative disorder that involves the death of motor neurons in the cortex, brain stem, and spinal cord. Adipose-derived stem cells (ADSCs) are considered as a perspective remedy for therapy of neurodegenerative diseases including ALS. Stem cells secrete various factors which can modulate a hostile environment, called paracrine effect. Exosomes are small extracellular vesicles containing cell derived factors and mediate paracrine effect of cells. Thus, exosomes from ADSCs (ADSC-exo) can be a potential candidate of therapeutic effects of stem cells. To investigate the effect of ADSC-exo on the cellular phenotypes of ALS, we used neuronal stem cells (NSCs), which can be differentiated into neuronal cells, isolated from wild type or G93A ALS mice model. ADSC-exo was treated to neuronal cells from G93A ALS mice model. Immunocytochemistry and dot-blot assay result showed that ADSC-exo alleviated aggregation of superoxide dismutase 1 (SOD1). Reduction of cytosolic SOD1 level by ADSC-exo was also confirmed by western blot. Mitochondria display various abnormalities in ALS and the decrease of phospho-CREB and PGC-1α were observed in the G93A cells. ADSC-exo treatment showed normalization of phospho-CREB/CREB ratio and PGC-1α expression level. Our results suggest that ADSC-exo modulates cellular phenotypes of ALS including SOD-1 aggregation and mitochondrial dysfunction, and can be a therapeutic candidate for ALS.


Assuntos
Adipócitos/citologia , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/terapia , Exossomos/metabolismo , Células-Tronco/citologia , Tecido Adiposo/citologia , Animais , Células Cultivadas , Citoplasma/metabolismo , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Transgênicos , Mitocôndrias/metabolismo , Neurônios Motores/metabolismo , Neurônios/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fenótipo , Superóxido Dismutase-1/metabolismo
8.
Am J Respir Crit Care Med ; 191(11): 1273-86, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25853696

RESUMO

RATIONALE: Pulmonary arterial hypertension is characterized by endothelial dysfunction, impaired bone morphogenetic protein receptor 2 (BMPR2) signaling, and increased elastase activity. Synthetic elastase inhibitors reverse experimental pulmonary hypertension but cause hepatotoxicity in clinical studies. The endogenous elastase inhibitor elafin attenuates hypoxic pulmonary hypertension in mice, but its potential to improve endothelial function and BMPR2 signaling, and to reverse severe experimental pulmonary hypertension or vascular pathology in the human disease was unknown. OBJECTIVES: To assess elafin-mediated regression of pulmonary vascular pathology in rats and in lung explants from patients with pulmonary hypertension. To determine if elafin amplifies BMPR2 signaling in pulmonary artery endothelial cells and to elucidate the underlying mechanism. METHODS: Rats with pulmonary hypertension induced by vascular endothelial growth factor receptor blockade and hypoxia (Sugen/hypoxia) as well as lung organ cultures from patients with pulmonary hypertension were used to assess elafin-mediated reversibility of pulmonary vascular disease. Pulmonary arterial endothelial cells from patients and control subjects were used to determine the efficacy and mechanism of elafin-mediated BMPR2 signaling. MEASUREMENTS AND MAIN RESULTS: In Sugen/hypoxia rats, elafin reduced elastase activity and reversed pulmonary hypertension, judged by regression of right ventricular systolic pressure and hypertrophy and pulmonary artery occlusive changes. Elafin improved endothelial function by increasing apelin, a BMPR2 target. Elafin induced apoptosis in human pulmonary arterial smooth muscle cells and decreased neointimal lesions in lung organ culture. In normal and patient pulmonary artery endothelial cells, elafin promoted angiogenesis by increasing pSMAD-dependent and -independent BMPR2 signaling. This was linked mechanistically to augmented interaction of BMPR2 with caveolin-1 via elafin-mediated stabilization of endothelial surface caveolin-1. CONCLUSIONS: Elafin reverses obliterative changes in pulmonary arteries via elastase inhibition and caveolin-1-dependent amplification of BMPR2 signaling.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo II/efeitos dos fármacos , Caveolina 1/efeitos dos fármacos , Elafina/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Inibidores de Proteases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Humanos , Miócitos de Músculo Liso/efeitos dos fármacos , Elastase Pancreática/efeitos dos fármacos , Ratos
9.
Nucleic Acids Res ; 42(3): 1628-43, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24234436

RESUMO

The remodeling of chromatin in the nucleolus is important for the control of ribosomal DNA (rDNA) transcription and ribosome biogenesis. Herein, we found that upstream binding factor (UBF) interacts with ESET, a histone H3K9 methyltransferase and is trimethylated at Lys (K) 232/254 by ESET. UBF trimethylation leads to nucleolar chromatin condensation and decreased rDNA transcriptional activity. UBF mutations at K232/254A and K232/254R restored rDNA transcriptional activity in response to ESET. Both ESET-ΔSET mutant and knockdown of ESET by short hairpin RNA reduced trimethylation of UBF and resulted in the restoration of rDNA transcription. Atomic force microscopy confirmed that UBF trimethylated by ESET modulates the plasticity of nucleolar chromatin. We further demonstrated that UBF trimethylation at K232/254 by ESET deregulates rDNA transcription in a cell model of Huntington's disease. Together, our findings show that a novel epigenetic modification of UBF is linked to impaired rDNA transcription and nucleolar chromatin remodeling, which may play key roles in the pathogenesis of neurodegeneration.


Assuntos
Nucléolo Celular/enzimologia , Nucléolo Celular/genética , DNA Ribossômico/metabolismo , Heterocromatina/química , Histona-Lisina N-Metiltransferase/metabolismo , Proteínas Pol1 do Complexo de Iniciação de Transcrição/metabolismo , Transcrição Gênica , Animais , Linhagem Celular , Humanos , Doença de Huntington/enzimologia , Metilação , Camundongos , Mutação , Proteínas Pol1 do Complexo de Iniciação de Transcrição/química , Proteínas Pol1 do Complexo de Iniciação de Transcrição/genética
10.
Biochem Biophys Res Commun ; 464(1): 236-43, 2015 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-26102026

RESUMO

Two DNA/RNA binding proteins, TDP-43 and FUS/TLSU, are involved in RNA processing, and their aberrant mutations induce inherited amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitinated inclusions. Wild type TDP-43 and FUS (wtTDP-43 and wtFUS) are mainly localized in the nucleus and biochemically interact with the microRNA processing enzyme Drosha. In this study, we investigated Drosha stability in Neuro 2A cells by gain and loss of function studies of wtTDP-43 and wtFUS and cycloheximide mediated protein degradation assay. We also generated three different phosphomimetic mutants of TDP-43 (S379E, S403/404E and S409/410E) by using a site-directed mutagenesis method and examined Drosha stability to elucidate a correlation between the phosphorylated TDP-43 mutants and Drosha stability. Overexpression of wtTDP-43 and/or wtFUS increased Drosha stability in Neuro 2A cells and double knockdown of wtTDP-43 and wtFUS reduced its stability. However, knockdown of wtTDP-43 or wtFUS did not affect Drosha stability in Neuro 2A cells. Interestingly, a phosphomimetic mutant TDP-43 (S409/410E) significantly reduced Drosha stability via prevention of protein-protein interactions between wtFUS and Drosha, and induced cytotoxicity in Neuro 2A cells. Our findings suggest that TDP-43 and FUS controls Drosha stability in Neuro 2A cells and that a phosphomimetic mutant TDP-43 (S409/410E) which is associated with Drosha instability can induce neuronal toxicity.


Assuntos
Proteínas de Ligação a DNA/genética , MicroRNAs/genética , Neurônios/metabolismo , Fosfoproteínas/genética , Proteína FUS de Ligação a RNA/genética , Ribonuclease III/genética , Animais , Morte Celular/genética , Linhagem Celular Tumoral , Cicloeximida/farmacologia , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/metabolismo , Estabilidade Enzimática/genética , Camundongos , MicroRNAs/metabolismo , Mimetismo Molecular , Mutagênese Sítio-Dirigida , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fosfoproteínas/metabolismo , Ligação Proteica , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Proteína FUS de Ligação a RNA/antagonistas & inibidores , Proteína FUS de Ligação a RNA/metabolismo , Ribonuclease III/metabolismo
11.
Animals (Basel) ; 14(2)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38254354

RESUMO

The Korean water deer (WD), a predominant wildlife species in South Korea, is listed as vulnerable by the IUCN Red List. Despite belonging to the same family, Cervidae, WD show significantly fewer adult ixodid tick infestations compared to roe deer (RD). Ticks, which cannot fly, engage in questing behavior in natural environments to latch onto hosts. They detect signals like body temperature and host skin chemicals to navigate through the hair coat to the preferred epidermis. In light of this, we performed an extensive comparative study of the skin tissue and hair characteristics of both deer species, focusing on elements contributing to the reduced tick bite incidence in WD. Remarkably, WD exhibited more prominent blood vessels, sebaceous glands, and sweat glands, which are crucial for skin barrier functions (p < 0.005). Moreover, WD had irregular scale patterns on their hair cuticles and possessed hair that was significantly stiffer and 2.83 times thicker than that of RD (p < 0.001). These characteristics potentially impede ticks from reaching the epidermis hair in WD and RD in the context of tick bite prevention. Further investigations in this area could enhance our understanding of tick-host dynamics and contribute to developing preventive measures against tick-borne diseases in other deer species.

12.
Eur J Surg Oncol ; 50(6): 108359, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38657377

RESUMO

BACKGROUND: Peritoneal recurrence is a significant cause of treatment failure after radical gastrectomy for gastric cancer. The prediction of metachronous peritoneal recurrence would have a significantly impact risk stratification and tailored treatment planning. This study aimed to externally validate the previously established PERI-Gastric 1 and 2 models to assess their generalizability in an independent population. METHODS: Retrospective external validation was conducted on a cohort of 8564 patients who underwent elective gastrectomy for stage Ib-IIIc gastric cancer between 1998 and 2018 at the Yonsei Cancer Center. Discrimination was tested using the area under the receiver operating characteristic curves (AUROC). Accuracy was tested by plotting observations against the predicted risk of peritoneal recurrence and analyzing the resulting calibration plots. Clinical usefulness was tested with a decision curve analysis. RESULTS: In the validation cohort, PERI-Gastric 1 and PERI-Gastric 2 exhibited an AUROC of 0.766 (95 % C.I. 0.752-0.778) and 0.767 (95 % C.I. 0.755-0.780), a calibration-in-the-large of 0.935 and 0.700, a calibration belt with a 95 % C.I. over the bisector in the risk range of 24%-33 % and 35%-47 %. The decision curve analysis revealed a positive net benefit in the risk range of 10%-42 % and 15%-45 %, respectively. CONCLUSIONS: This study presents the external validation of the PERI-Gastric 1 and 2 scores in an Eastern population. The models demonstrated fair discrimination and satisfactory calibration for predicting the risk of peritoneal recurrence after radical gastrectomy, even in Eastern patients. PERI-Gastric 1 and 2 scores could also be applied to predict the risk of metachronous peritoneal recurrence in Eastern populations.


Assuntos
Gastrectomia , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , República da Coreia/epidemiologia , Medição de Risco , Idoso , Curva ROC , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Bases de Dados Factuais , Área Sob a Curva
13.
Acta Neuropathol ; 125(5): 727-39, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23455440

RESUMO

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by an expanded trinucleotide CAG repeat in the gene coding for huntingtin. Deregulation of chromatin remodeling is linked to the pathogenesis of HD but the mechanism remains elusive. To identify what genes are deregulated by trimethylated histone H3K9 (H3K9me3)-dependent heterochromatin, we performed H3K9me3-ChIP genome-wide sequencing combined with RNA sequencing followed by platform integration analysis in stable striatal HD cell lines (STHdhQ7/7 and STHdhQ111/111) cells. We found that genes involving neuronal synaptic transmission including cholinergic receptor M1 (CHRM1), cell motility, and neuronal differentiation pathways are downregulated while their promoter regions are highly occupied with H3K9me3 in HD. Moreover, we found that repression of CHRM1 gene expression by H3K9me3 impairs Ca(2+)-dependent neuronal signal transduction in stable cell lines expressing mutant HD protein. Thus, our data indicate that the epigenetic modifications, such as aberrant H3K9me3-dependent heterochromatin plasticity, directly contribute to the pathogenesis of HD.


Assuntos
Sinalização do Cálcio/fisiologia , Epigênese Genética/fisiologia , Histonas/fisiologia , Doença de Huntington/etiologia , Doença de Huntington/metabolismo , Receptores Muscarínicos/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Humanos , Proteína Huntingtina , Camundongos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Plasticidade Neuronal/fisiologia , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Receptor Muscarínico M1 , Receptores Muscarínicos/genética
14.
Front Oncol ; 13: 1140175, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36895483

RESUMO

Introduction: Abdominal computed tomography (CT) can accurately demonstrate organs and vascular structures around the stomach, and its potential role for image guidance is becoming increasingly established. However, solely using two-dimensional CT images to identify critical anatomical structures is undeniably challenging and not surgeon-friendly. To validate the feasibility of a patient-specific 3-D surgical navigation system for preoperative planning and intraoperative guidance during robotic gastric cancer surgery. Materials and methods: A prospective single-arm open-label observational study was conducted. Thirty participants underwent robotic distal gastrectomy for gastric cancer using a virtual surgical navigation system that provides patient-specific 3-D anatomical information with a pneumoperitoneum model using preoperative CT-angiography. Turnaround time and the accuracy of detecting vascular anatomy with its variations were measured, and perioperative outcomes were compared with a control group after propensity-score matching during the same study period. Results: Among 36 registered patients, 6 were excluded from the study. Patient-specific 3-D anatomy reconstruction was successfully implemented without any problems in all 30 patients using preoperative CT. All vessels encountered during gastric cancer surgery were successfully reconstructed, and all vascular origins and variations were identical to operative findings. The operative data and short-term outcomes between the experimental and control group were comparable. The experimental group showed shorter anesthesia time (218.6 min vs. 230.3 min; P=0.299), operative time (177.1 min vs. 193.9 min; P=0.137), and console time (129.3 min vs. 147.4 min; P=0.101) than the control group, although the differences were not statistically significant. Conclusions: Patient-specific 3-D surgical navigation system for robotic gastrectomy for gastric cancer is clinically feasible and applicable with an acceptable turnaround time. This system enables patient-specific preoperative planning and intraoperative navigation by visualizing all the anatomy required for gastrectomy in 3-D models without any error. Clinical trial registration: Clinicaltrials.gov, identifier NCT05039333.

15.
VideoGIE ; 8(9): 342-347, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37719947

RESUMO

Video 1Management of a gastric pouch staple-line leak and its adverse events with multimodal endoscopic techniques including endoscopic vacuum therapy.

16.
J Gastric Cancer ; 23(2): 253-263, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37129150

RESUMO

PURPOSE: Although chylous ascites is a frequent complication of radical gastrectomy for gastric cancer, proper diagnostic criteria and optimal treatment strategies have not been established. This study aimed to identify the clinical features of chylous ascites and evaluate the treatment outcomes. MATERIALS AND METHODS: We retrospectively analyzed the data of patients who underwent radical gastrectomy between 2013 and 2019. Diagnosis was made when milky fluid or elevated triglyceride levels (≥100 mg/dL) appeared in the drains without a preceding infection. The clinical features, risk factors, and treatment outcomes were assessed according to the initial treatment modalities for fasting and non-fasting groups. RESULTS: Among the 7,388 patients who underwent radical gastrectomy for gastric cancer, 156 (2.1%) experienced chylous ascites. The median length of hospital stay was longer in patients with chylous ascites than in those without (median [interquartile range]: 8.0 [6.0-12.0] vs. 6.0 [5.0-8.0], P<0.001). Low body mass index (adjusted odds ratio [aOR]=0.9; P<0.001), advanced gastric cancer (aOR=1.51, P=0.024), open surgery (reference: laparoscopic surgery; aOR=1.87, P=0.003), and extent of surgical resection (reference: subtotal gastrectomy, total gastrectomy, aOR=1.5, P=0.029; proximal gastrectomy, aOR=2.93, P=0.002) were associated with the occurrence of chylous ascites. The fasting group (n=12) was hospitalized for a longer period than the non-fasting group (n=144) (15.0 [12.5-19.5] vs. 8.0 [6.0-10.0], P<0.001). There was no difference in grade III complication rate (16.7% vs. 4.2%, P=0.117) or readmission rate (16.7% vs. 11.1%, P=0.632) between the groups. CONCLUSIONS: A fat-controlled diet and medication without fasting provided adequate initial treatment for chylous ascites after radical gastrectomy for gastric cancer.

17.
Int J Surg ; 109(10): 2926-2933, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37352518

RESUMO

BACKGROUND: Fluorescent lymphography-guided lymphadenectomy (FL) for gastric cancer is gaining popularity. However, its impact on prognosis is not known. This study aimed to assess the prognostic impact of FL in gastric cancer patients. MATERIALS AND METHODS: This study retrospectively analyzed 5678 gastric cancer patients who underwent gastrectomy from 2013 to 2017. The survival was compared between the FLFL group and the conventional lymphadenectomy (non-FL group) using 1:1 propensity score matching after exclusion. Patients in the FL group underwent gastrectomy with systematic lymphadenectomy after endoscopic peritumoral injection of indocyanine green the day before surgery. RESULTS: After propensity score matching, the FL and non-FL groups each had 1064 patients with similar demographic and clinicopathological characteristics. All matched variables had a standardized mean difference under 0.1. The FL group showed a significantly higher number of retrieved lymph nodes (56.2±20.1) than the non-FL group (46.2±18.2, P <0.001). The FL group also had more stage III patients ( P= 0.044) than the non-FL group. The FL group demonstrated higher overall survival ( P= 0.038) and relapse-free survival ( P= 0.036) in stage III compared with the non-FL group. However, no significant differences in overall and relapse-free survival were observed between the two groups for stages I ( P= 0.420 and P= 0.120, respectively) and II ( P= 0.200 and P= 0.280, respectively). CONCLUSION: FL demonstrated a higher survival in stage III gastric cancer patients by the more accurate staging resulting from larger lymph node retrieval. Thus, given its potential to improve prognostication by enhancing staging accuracy, it is recommended as an option to consider the use of FL in clinical practice.


Assuntos
Linfografia , Neoplasias Gástricas , Humanos , Prognóstico , Linfografia/métodos , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Linfonodos/patologia , Excisão de Linfonodo/métodos , Corantes , Gastrectomia/métodos , Estadiamento de Neoplasias
18.
Sci Rep ; 13(1): 5252, 2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-37002330

RESUMO

Failure to rescue (FTR), the mortality rate among patients with complications, is gaining attention as a hospital quality indicator. However, comprehensive investigation into FTR has rarely been conducted after radical gastrectomy for gastric cancer patients. This study aimed to assess FTR after radical gastrectomy and investigate the associations between FTR and clinicopathologic factors, operative features, and complication types. From 2006 to 2021, 16,851 gastric cancer patients who underwent gastrectomy were retrospectively analyzed. The incidence and risk factors were analyzed for complications, mortality, and FTR. Seventy-six patients had postoperative mortality among 15,984 patients after exclusion. The overall morbidity rate was 10.49% (1676/15,984 = 10.49%), and the FTR rate was 4.53% (76/1676). Risk factor analysis revealed that older age (reference: < 60; vs. 60-79, adjusted odds ratio [OR] 2.07, 95% confidence interval [CI] 1.13-3.79, P = 0.019; vs. ≥ 80, OR 3.74, 95% CI 1.57-8.91, P = 0.003), high ASA score (vs. 1 or 2, OR 2.79, 95% CI 1.59-4.91, P < 0.001), and serosa exposure in pathologic T stage (vs. T1, OR 2.74, 95% CI 1.51-4.97, P < 0.001) were associated with FTR. Moreover, patients who underwent gastrectomy during 2016-2021 were less likely to die when complications occurred than patients who received the surgery in 2006-2010 (OR 0.35, 95% CI 0.18-0.68, P = 0.002). This investigation of FTR after gastrectomy demonstrated that the risk factors for FTR were old age, high ASA score, serosa exposure, and operation period. FTR varied according to the complication types and the period, even in the same institution.


Assuntos
Complicações Pós-Operatórias , Neoplasias Gástricas , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/complicações , Fatores de Risco , Gastrectomia/efeitos adversos , República da Coreia/epidemiologia , Mortalidade Hospitalar
19.
Sci Rep ; 13(1): 9355, 2023 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-37291374

RESUMO

To overcome the limitations of laparoscopic surgery, robotic systems have been commonly used in the era of minimally invasive surgery despite their high cost. However, the articulation of instruments can be achieved without a robotic system at lower cost using articulating laparoscopic instruments (ALIs). Between May 2021 and May 2022, perioperative outcomes following laparoscopic gastrectomy using ALIs versus robotic gastrectomy were compared. A total of 88 patients underwent laparoscopic gastrectomy using ALIs, while 96 underwent robotic gastrectomy. Baseline characteristics were similar between the groups except for a higher proportion of patients with a medical history in the ALI group (p = 0.013). Clinicopathologic and perioperative outcomes were not significantly different between the groups. However, the operation time was significantly shorter in the ALI group (p = 0.026). No deaths occurred in either group. In conclusion, laparoscopic gastrectomy using ALIs was associated with comparable perioperative surgical outcomes and a shorter operation time compared to robotic gastrectomy in this prospective cohort study.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Humanos , Estudos Prospectivos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Análise Custo-Benefício , Estudos Retrospectivos , Gastrectomia , Resultado do Tratamento , Complicações Pós-Operatórias/cirurgia
20.
Sci Rep ; 13(1): 18578, 2023 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-37903856

RESUMO

Minimally invasive surgery reduces surgical trauma and the size and number of incisions. The da Vinci SP robotic surgical system was designed to overcome the technical demands of single-incision laparoscopic surgery. This study aimed to demonstrate the safety and feasibility of single-port (SP) robotic distal gastrectomy (SPRDG) for patients with gastric cancer using the da Vinci SP system (Intuitive Surgical Inc., Sunnyvale, CA, USA). This study was designed as a single-arm prospective phase I/II clinical trial of SPRDG (first posted date: 21/09/2021, NCT05051670; clinicaltrials.gov). SPRDG using the da Vinci SP system was performed on 19 patients with gastric cancer between December 2021 and October 2022. The primary outcome was the safety of SPRDG as measured by major postoperative complications. The secondary outcomes were operation time, bleeding amount, bowel motility recovery, and length of hospital stay. SPRDG was performed in all 19 patients without unexpected events, such as use of additional trocars or conversion to laparoscopic or open surgery. No major complications occurred postoperatively (0/19, 0.0%). The mean operation time was 218 min (range 164-286 min). The mean hospital stay duration was 3.2 days (range 2-4 days). This phase I/II clinical trial, performed by a single expert surgeon, demonstrated the safety and feasibility of SPRDG with the da Vinci SP system in selected patients with gastric cancer. SPRDG could be a reasonable alternative to conventional or reduced-port minimally invasive gastrectomy, as it has cosmetic advantages, early recovery, and safe discharge.


Assuntos
Gastrectomia , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Humanos , Estudos de Viabilidade , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Laparoscopia , Estudos Prospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Gástricas/cirurgia
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