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1.
Cancer Commun (Lond) ; 41(3): 258-272, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33570246

RESUMO

BACKGROUND: Insulin gene enhancer protein 1, (ISL1), a LIM-homeodomain transcription factor, is involved in multiple tumors and is associated with insulin secretion and metabolic phenotypes. However, the role of ISL1 in stimulating glycolysis to promote tumorigenesis in gastric cancer (GC) is unclear. In this study, we aimed to characterize the expression pattern of ISL1 in GC patients and explore its molecular biological mechanism in glycolysis and tumorigenesis. METHODS: We analyzed the expression and clinical significance of ISL1 in GC using immunohistochemistry and real-time polymerase chain reaction (PCR). Flow cytometry and IncuCyte assays were used to measure cell proliferation after ISL1 knockdown. RNA-sequencing was performed to identify differentially expressed genes, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA) to reveal key signaling pathways likely regulated by ISL1 in GC. Alteration of the glycolytic ability of GC cells with ISL1 knockdown was validated by measuring the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) and by detecting glucose consumption and lactate production. The expression of glucose transporter 4 (GLUT4) and ISL1 was assessed by Western blotting, immunohistochemistry, and immunofluorescent microscopy. The luciferase reporter activity and chromatin immunoprecipitation assays were performed to determine the transcriptional regulation of ISL1 on GLUT4. RESULTS: High levels of ISL1 and GLUT4 expression was associated with short survival of GC patients. ISL1 knockdown inhibited cell proliferation both in vitro and in vivo. KEGG analysis and GSEA for RNA-sequencing data indicated impairment of the glycolysis pathway in GC cells with ISL1 knockdown, which was validated by reduced glucose uptake and lactate production, decreased ECAR, and increased OCR. Mechanistic investigation indicated that ISL1 transcriptionally regulated GLUT4 through binding to its promoter. CONCLUSION: ISL1 facilitates glycolysis and tumorigenesis in GC via the transcriptional regulation of GLUT4.

2.
Mol Ther Nucleic Acids ; 22: 1129-1141, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33294297

RESUMO

Long non-coding RNAs (lncRNAs) are characterized as key layers of the genome in various cancers. TSPEAR-AS2 was highlighted to be a candidate lncRNA potentially involved in gastric cancer (GC) progression. However, the clinical significance and mechanism of TSPEAR-AS2 in GC required clarification. The clinical significance of TSPEAR-AS2 was elucidated through Kaplan-Meier Plotter. The mechanism of TSPEAR-AS2 in GC was clarified in vitro and in vivo using luciferase reporter, chromatin immunoprecipitation, RNA immunoprecipitation assays, and animal models. TSPEAR-AS2 elevation was closely correlated with overall survival of GC patients. A basic transcription element-binding protein 2 (BTEB2)-activated TSPEAR-AS2 model was first explored in this study. TSPEAR-AS2 silencing substantially reduced tumorigenic capacities of GC cells, while TSPEAR-AS2 elevation had the opposite effect. Mechanistically, TSPEAR-AS2 bound with both polycomb repressive complex 2 (PRC2) and argonaute 2 (Ago2). TSPEAR-AS2 knockdown significantly decreased H3K27me3 levels at promoter regions of gap junction protein alpha 1 (GJA1). Ago2 was recruited by TSPEAR-AS2, which was defined to sponge miR-1207-5p, contributing to the repression of claudin 4 (CLDN4) translation. The axis of EZH2/GJA1 and miR-1207-5p/CLDN4 mediated by BTEB2-activated-TSPEAR-AS2 plays an important role in GC progression, suggesting a new therapeutic direction in GC treatment.

3.
J Gastrointest Oncol ; 11(5): 894-898, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209485

RESUMO

Background: The purpose of this study was to evaluate the health economics of patients with sepsis after gastrointestinal tumor operation in ICU. Methods: This case-control study used 1:1 propensity-score (PS) matched method and patients were matched according to tumor type, age and gender. The study group was composed of 181 patients with sepsis after operation of gastrointestinal tumor in ICU, while the control group was composed of 181 patients without sepsis after operation of gastrointestinal tumor. The medical expenses and length of stay in the hospital of these patients were analyzed. Results: The median of the total hospitalization cost for the study group was $26,038, which was 1.7 times of the control group (P<0.001). The costs of drugs, laboratory test, examination, treatment, operation, anesthesia, materials, ward and other costs in the study group were higher than those in the control group (P<0.001). The median length of stay in the hospital in the study group was 26 days, which were 12 days longer than that of the control group (P<0.001). However, there was no significant difference in daily average cost between the two groups (P=0.103). Conclusions: In ICU, patients with sepsis after operation of gastrointestinal tumor increased the cost of hospitalization and prolonged the length of stay in the hospital than those without sepsis.

4.
Gastric Cancer ; 2020 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-32712769

RESUMO

BACKGROUND: For patients with locally advanced proximal gastric cancer (LAPGC), the individualized selection of patients with highly suspected splenic hilar (No. 10) lymph node (LN) metastasis to undergo splenic hilar lymphadenectomy, is a clinical dilemma. This study aimed to re-evaluate the feasibility and safety of laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) and to identify the population who would benefit from it. METHODS: A total of 1068 patients (D2 group = 409; D2 + No. 10 group = 659) who underwent laparoscopic total gastrectomy from four prospective trials between January 2015 and July 2019 were analyzed. RESULTS: No significant difference in the incidence (16.9% vs. 16.4%; P = 0.837) of postoperative complications were found between the two groups. The metastasis rate of No. 10 LN among patients in the D2 + No. 10 group was 10.3% (68/659). Based on the decision tree, patients with LAPGC with tumor invading the greater curvature (Gre), patients with non-Gre-invading LAPGC with a tumor size > 5 cm and clinical positive locoregional LNs were defined as the high-priority No. 10 dissection group. The metastasis rate of No. 10 LNs in the high-priority group was 19.4% (41/211). In high-priority group, the 3-year overall survival of the D2 + No. 10 group was better than that of the D2 group (74.4% vs. 42.1%; P = 0.005), and the therapeutic index of No. 10 was higher than the indices of most suprapancreatic stations. CONCLUSIONS: LSPSHL for LAPGC is safe and feasible when performed by experienced surgeons. LSPSHL could be recommended for the high-priority group patients even without invasion of the Gre.

5.
Gastroenterol Rep (Oxf) ; 8(3): 167-174, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32661490

RESUMO

Novel coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing public-health pandemic worldwide. Although SARS-CoV-2 has been known to spread primarily through respiratory droplets, recent evidence also supports fecal/oral as an additional route of transmission, raising concerns over gastrointestinal (GI) transmission of the infection. Herein, we, as the front-line Chinese GI surgeons, would like to share our experience and lessons in the combat against COVID-19. It is essential to create science-based, rational, and practical strategies during the outbreak of COVID-19. Here, we provide multi-institutional consensus on minimizing disease transmission while continuing to provide care from all aspects for patients in GI surgery, including outpatient clinics, inpatient units, gastrointestinal endoscopy centers, and adjustments in perioperative care. Our experiences and recommendations are worth sharing and may help to establish specific infection-control and outcome measures.

6.
Sci Transl Med ; 12(549)2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32581131

RESUMO

Several patient-derived tumor models emerged recently as robust preclinical drug-testing platforms. However, their potential to guide clinical therapy remained unclear. Here, we report a model called patient-derived tumor-like cell clusters (PTCs). PTCs result from the self-assembly and proliferation of primary epithelial, fibroblast, and immune cells, which structurally and functionally recapitulate original tumors. PTCs enabled us to accomplish personalized drug testing within 2 weeks after obtaining the tumor samples. The defined culture conditions and drug concentrations in the PTC model facilitate its clinical application in precision oncology. PTC tests of 59 patients with gastric, colorectal, or breast cancers revealed an overall accuracy of 93% in predicting their clinical outcomes. We implemented PTC to guide chemotherapy selection for a patient with mucinous rectal adenocarcinoma who experienced recurrence with metastases after conventional therapy. After three cycles of a nonconventional therapy identified by the PTC, the patient showed a positive response. These findings need to be validated in larger clinical trials, but they suggest that the PTC model could be prospectively implemented in clinical decision-making for therapy selection.

7.
Gastric Cancer ; 23(6): 1041-1050, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32500456

RESUMO

BACKGROUND: Early diagnosis of Peritoneal metastasis (PM) is clinically significant regarding optimal treatment selection and avoidance of unnecessary surgical procedures. Cytopathology plays an important role in early screening of PM. We aimed to develop a deep learning (DL) system to achieve intelligent cytopathology interpretation, especially in ascites cytopathology. METHODS: The original ascites cytopathology image dataset consists of 139 patients' original hematoxylin-eosin (HE) and Papanicolaou (PAP) Staining images. DL system was developed using transfer learning (TL) to achieve cell detection and classification. Pre-trained alexnet, vgg16, goolenet, resnet18 and resnet50 models were studied. Cell detection dataset consists of 176 cropped images with 6573 annotated cell bounding boxes. Cell classification data set consists of 487 cropped images with 18,558 and 6089 annotated malignant and benign cells in total, respectively. RESULTS: We established a novel ascites cytopathology image dataset and achieved automatically cell detection and classification. DetectionNet based on Faster R-CNN using pre-trained resnet18 achieved cell detection with 87.22% of cells' Intersection of Union (IoU) bigger than the threshold of 0.5. The mean average precision (mAP) was 0.8316. The ClassificationNet based on resnet50 achieved the greatest performance in cell classification with AUC = 0.8851, Precision = 96.80%, FNR = 4.73%. The DL system integrating the separately trained DetectionNet and Classificationnet showed great performance in the cytopathology image interpretation. CONCLUSIONS: We demonstrate that the integration of DL can improve the efficiency of healthcare. The DL system we developed using TL techniques achieved accurate cytopathology interpretation, and had great potential to be integrated into clinician workflow.

8.
Eur J Radiol ; 128: 108974, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32416553

RESUMO

PURPOSE: To assess the efficacy of diffusion kurtosis imaging (DKI) in the prediction of the treatment response to neoadjuvant chemotherapy in patients with locally advanced gastric cancer (LAGC). METHODS: A total of 31 LAGC patients were enrolled in this prospective study. All patients underwent diffusion-weighted MRI examination (with b = 01, 2001, 5001, 8002, 10004, 15004, 20006 s/mm2, the subscript denotes the number of signal averages) before and after chemotherapy. DKI and mono-exponential (b = 0, 800 s/mm2) models were built. Apparent diffusion coefficient (ADC), mean diffusivity (MD) and mean kurtosis (MK) of the LAGC tumors were measured. The absolute change values (ΔX) and percentage change values (%ΔX) of the above parameters post neoadjuvant chemotherapy (NACT) were calculated. The response was evaluated according to the pathological tumor regression grade scores (effective response group: TRG 0-2, poor response group: TRG 3). Mann-Whitney U test and receiver operating characteristic (ROC) curves were applicated for statistical analysis. RESULTS: There were 17 patients in the effective response group (ERG), and 14 patients in the poor response group (PRG). The MKpre and MKpost values in PRG were significantly higher than those in ERG [(0.671 ±â€¯0.026) and (0.641 ±â€¯0.019) vs. (0.584 ±â€¯0.023) and (0.519 ±â€¯0.018), p < 0.001]. ADCpost and MDpost in PRG were significantly lower than those in ERG (p = 0.005, p =0.001). Significant differences were also observed for % ΔMK, ΔMD and ΔMK between the two groups (p < 0.05). The area under the curve (AUC) for the prediction of PRG was highest for MKpost (AUC = 0.958, cutoff value = 0.614). The MKpre and MKpost had the highest sensitivity (91.70 %) and specificity (93.80 %) in the prediction of PRG, respectively. CONCLUSION: Both DKI and ADC values show potential for the prediction of the PRG in LAGC patients. The DKI parameters, especially MKpost displayed the best performance.

9.
J Laparoendosc Adv Surg Tech A ; 30(7): 713-722, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32471317

RESUMO

Background: With the rapid aging of global population, the number of elderly patients with gastric cancer is increasing. This study aimed to evaluate short- and long-term outcomes after laparoscopic gastrectomy (LG) versus open gastrectomy (OG) in elderly gastric cancer patients. Materials and Methods: We searched PubMed, EMBASE, and the Cochrane library databases from January 1994 to May 2019. Surgical safety, postoperative complications, number of harvested lymph nodes, and overall survival rate were included and analyzed. The qualities of the included studies were evaluated by Newcastle-Ottawa Quality Assessment Scale. The evidence of outcomes was evaluated using the GRADE approach. The Review Manager® 5.3 (Cochrane, London, UK) and Stata® 14.0 (StataCorp., College Station, Texas) were used to analyze the outcomes. Results: Thirteen studies containing 4768 elderly patients with gastric cancer were included in this meta-analysis. LG was more favorable than OG in terms of overall postoperative morbidity (odds ratio [OR]: 0.56; 95% confidence interval [CI]: 0.44 to 0.70; P < .00001), the postoperative stay (standardized mean difference [SMD]: -0.56; 95% CI: -0.76 to (-0.37); P < .00001), and the number of harvested lymph nodes (SMD: 0.19; 95% CI: 0.09 to 0.29; P = .0003). No significant difference was found in anastomotic leakage rate (OR: 0.82; 95% CI: 0.59 to 1.12; P = .21), mental disease (OR: 0.79; 95% CI: 0.44 to 1.44; P = .44), or overall survival rate (P = .62) between two groups. However, in the subgroup with a cutoff age of 80 years, the anastomotic leakage rate was higher in LG (OR: 10.27; 95% CI: 1.31 to 80.35; P = .03). Conclusions: LG was more favorable than OG in the elderly patients <80 years old with gastric cancer.

10.
Ann Surg Oncol ; 27(4): 1103-1109, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31965376

RESUMO

BACKGROUND: Preoperative diagnosis of peritoneal metastasis with gastric cancer remains challenging. This study explored the abnormal computed tomography (CT) signs of occult peritoneal metastasis (OPM) and evaluated it by region-to-region comparison using staging laparoscopy, from which a 4-point CT score system was developed. METHODS: Patients with advanced gastric cancer (stage cT ≥ 2M0) diagnosed by CT were enrolled in the study. Occult peritoneal metastasis detected during staging laparoscopy was compared with preoperative CT to investigate the presence of abnormal signs by a region-to-region comparison. A 4-point CT score system was developed to define the radiologic characteristics. Subsequently, the diagnostic efficacy of the CT score system was prospectively verified. RESULTS: In this study, 57 OPM regions were detected by staging laparoscopy in 33 of the 385 enrolled patients. The greater omentum was the most frequent site of OPM (38.60%, 22/57), which usually exhibited a smudge-like ground-glass opacity (S-GGO) (90.91%, 20/22) with a mean CT score of 2.14. The parietal and perihepatic peritoneum was the second most common site (22.81%, 13/57). A 4-point CT score system was developed based on the results. A cutoff CT score of 2 or higher was associated with a false-negative rate of 2% (2/99). This CT score system had a sensitivity of 87.5% and a specificity of 76.4% for an OPM-positive diagnosis (area under the curve, 0.848). The agreement between two radiologists on the assigned final score was 76.2% (kappa, 0.5). CONCLUSIONS: Patients with OPM mostly exhibited S-GGO on CT, which should be interpreted cautiously. The 4-point CT score system may improve the pretreatment evaluation of occult peritoneal metastasis, and staging laparoscopy might not be necessary for patients with a score lower than 2.

11.
Surg Endosc ; 34(11): 5062-5073, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31823047

RESUMO

BACKGROUND: Previous retrospective studies have shown that laparoscopic spleen-preserving D2 total gastrectomy (LSTG) for advanced upper third gastric cancer (AUTGC) is safe. However, all previous studies were underpowered. We therefore conducted a prospective, multicenter study to evaluate the technical safety and feasibility of LSTG for patients with AUTGC. METHODS: Patients diagnosed with AUTGC (cT2-4a, N-/+, M0) underwent LSTG at 19 institutions between September 2016 and October 2017 were included. The number of No. 10 lymph node (LN) dissections, metastasis rates, intraoperative and postoperative complications were investigated. RESULTS: A total of 251 patients were enrolled in the study, and 242 patients were eligible for the per protocol analysis. The average numbers of No. 10 LN dissections and metastases were 2.4 and 0.1, respectively. Eighteen patients (7.4%) had No. 10 LN metastases, and among patients with advanced gastric cancer, the rate of No. 10 LN metastasis was 8.1% (18/223). pN3 status was an independent risk factor for No. 10 LN metastasis. Intraoperative complications occurred in 7 patients, but no patients required conversion to open surgery or splenectomy. The overall postoperative complication rate was 13.6% (33/242). The major complication and mortality rates were 3.3% (8/242) and 0.4% (1/242), respectively. The number of retrieved No. 10 LNs, No. 10 LN metastasis and TNM stage had no significant influence on postoperative complication rates. CONCLUSION: LSTG for AUTGC was safe and effective when performed by very experienced surgeons, this technique could be used in patients who needed splenic hilar lymph node dissection.

12.
Surg Endosc ; 34(3): 1191-1199, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31236721

RESUMO

OBJECTIVES: Healing of gastric endoscopic submucosal dissection (ESD)-induced ulcer is critical for patient recovery. During ESD treatment, submucosal incisions are made with an electrosurgical knife to accomplish en bloc resections of superficial lesions. Nevertheless, excess electrocoagulation may decrease the blood supply of ESD-induced ulcer and delay the ulcer healing. The aim of this retrospective study was to evaluate the effectiveness of conservative electrocoagulation followed by porcine fibrin sealant (FS) as a wound microvessels-protective hemostatic technique in promoting the healing of ESD-induced ulcer. METHODS: A total of 332 patients with early gastric cancer (EGCs), or gastric precancerous lesion and gastric adenoma were retrospectively analyzed. Propensity score matching was used to compensate for the differences in age, gender, tumor location, resected specimen area, and pathology. One-month ulcer healing rates and delayed bleeding were compared between two matched groups (combined hemostats group and electrocautery group). RESULTS: A total of 115 matched pairs were created after propensity score matching. There was no difference in tumor location, specimen surface area, tumor differentiation and invasion depth between groups. The completed healing rate 1 month after ESD was 44.3% in combined hemostats group and 30.4% in electrocautery group (P = 0.004). There was no difference in delayed massive bleeding rate between two groups (P = 0.300). In addition, based on the multivariate regression analysis for ulcer healing rate, the use of FS (OR, 0.348, 95% CI 0.196 - 0.617, P = 0.000) and larger specimen size (OR, 2.640, 95% CI 2.015-3.458, P = 0.000) were associated with nonhealing ulcer 1 month after ESD. CONCLUSION: Applying conservative electrocoagulation followed by porcine FS as a wound microvessels-protective hemostatic technique can promote ESD-induced ulcer healing without increasing delayed bleeding.

13.
Chin J Cancer Res ; 31(5): 771-784, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31814681

RESUMO

Objective: Tumor heterogeneity renders identification of suitable biomarkers of gastric cancer (GC) challenging. Here, we aimed to identify prognostic genes of GC using computational analysis. Methods: We first used microarray technology to profile gene expression of GC and paired nontumor tissues from 198 patients. Based on these profiles and patients' clinical information, we next identified prognostic genes using novel computational approaches. Phosphoglucose isomerase, also known as glucose-6-phosphate isomerase (GPI), which ranked first among 27 candidate genes, was further investigated by a new analytical tool namely enviro-geno-pheno-state (E-GPS) analysis. Suitability of GPI as a prognostic marker, and its relationship with physiological processes such as metabolism, epithelial-mesenchymal transition (EMT), as well as drug sensitivity were evaluated using both our own and independent public datasets. Results: We found that higher expression of GPI in GC correlated with prolonged survival of patients. Particularly, a combination of CDH2 and GPI expression effectively stratified the outcomes of patients with TNM stage II/III. Down-regulation of GPI in tumor tissues correlated well with depressed glucose metabolism and fatty acid synthesis, as well as enhanced fatty acid oxidation and creatine metabolism, indicating that GPI represents a suitable marker for increased probability of EMT in GC cells. Conclusions: Our findings strongly suggest that GPI acts as a novel biomarker candidate for GC prognosis, allowing greatly enhanced clinical management of GC patients. The potential metabolic rewiring correlated with GPI also provides new insights into studying the relationship between cancer metabolism and patient survival.

14.
Sci Rep ; 9(1): 15339, 2019 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653890

RESUMO

Vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) plays a crucial role in breakdown of the blood-retinal barrier due to hyperpermeability in diabetic retinopathy (DR). However, the distinct signaling driven by VEGF and PlGF in the pathogenesis of DR remains unclear. In this study, we investigated VEGF- and PlGF- related signaling pathways and their roles in cultured human microvascular retinal endothelial cells (hRECs) under high glucose conditions (HG; 25 mM). Apoptotic cell death was evaluated, and FITC conjugated bovine serum albumin across monolayer hRECs served as an index of permeability. Western blots were used to assess the protein levels of VEGF and PlGF, as well as the phosphorylation of p38MAPK, STAT1 and Erk1/2. Knockdown of VEGF and PlGF was performed by using siRNA. Following HG treatment, increases of VEGF and PlGF as well as PKC activity were detected in hRECs. Increased phosphorylations of p38MAPKThr180/Thr182, STAT1Ser727, and Erk1/2Tyr202/Tyr185 as well as VEGFR1Tyr1213 and VEGFR2Tyr1175 were also detected in HG-treated hRECs. Inhibition of PKC activity by Go 6976 prevented HG-induced increases of phosphor-Erk1/2 and nitric oxide synthase (NOS1) expressions as well as hyperpermeability, whereas inhibition of p38MAPK pathway by SB203580 selectively suppressed activation of STAT1 and decreased apoptotic cell death under HG conditions. Moreover, VEGF knockdown predominantly inhibited activation of VEGFR2, and phosphorylation of p38MAPK and STAT1, as well as apoptotic cell death in HG-treated hRECs. Nevertheless, PlGF knockdown mainly suppressed phosphorylation of VEGFR1, PKC, and Erk1/2, as well as NOS1 expressions and hyperpermeability. Taken together, we provide evidence demonstrating that HG-induced elevation of PlGF is responsible for hyperpermeability mainly through increasing activation of PKC-Erk1/2-NOS axis via VEGFR1, while HG-induced elevation of VEGF is associated with induction of apoptotic cell death mainly through increasing activation of p38MAPK/STAT1 signaling via VEGFR2.


Assuntos
Células Endoteliais/patologia , Glucose/toxicidade , Fator de Crescimento Placentário/metabolismo , Retina/patologia , Transdução de Sinais , Fatores de Crescimento do Endotélio Vascular/metabolismo , Apoptose/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Modelos Biológicos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
15.
Asia Pac J Clin Nutr ; 28(3): 442-449, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31464390

RESUMO

BACKGROUND AND OBJECTIVES: The association between skeletal muscle status and gastric cancer (GC) prognosis remains unclear. Here, we investigated the impact of the skeletal muscle index (SMI) on overall survival (OS) in GC patients after radical gastrectomy. METHODS AND STUDY DESIGN: We divided 178 patients into four groups: adult men, adult women, elderly men and elderly women. The SMI, calculated using CT images, of patients was graded using cutoff values of group-specific tertiles. Age, body mass index, SMI grade, Charlson comorbidity index, surgical method (total vs distal gastrectomy), tumor stage, and histological type and differentiation were included in Cox regression models to assess the primary outcome parameter of OS. A new prognostic score for 3- year OS was established by combining the SMI grade and tumor stage, and receiver operating characteristic (ROC) curve analyses were used to determine its predictive reliability. RESULTS: For groups with high, medium, and low SMI grades, the 3-year OS rates were 94.04, 79.08 and 59.09% and 86.09, 70.11 and 49.11% (p<0.001) in patients undergoing distal and total gastrectomy, respectively. In the multivariate analysis, low SMI (hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.14-2.9), advanced stage (HR 2.89, 95% CI 1.43-5.83), and total gastrectomy (HR 1.69, 95% CI 0.95-3.01) were independent risk factors for OS (p<0.010). The areas under the ROC curves for the prognostic score were 0.77 (range 0.61-0.93) and 0.76 (range 0.65-0.86) in patients undergoing distal and total gastrectomy, respectively. CONCLUSIONS: The preoperative SMI was an independent prognostic factor for long-term survival in GC patients after radical gastrectomy.


Assuntos
Gastrectomia/efeitos adversos , Músculo Esquelético/fisiologia , Neoplasias Gástricas/complicações , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sarcopenia , Análise de Sobrevida
16.
Cancer Manag Res ; 11: 5375-5391, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354346

RESUMO

Purpose: Emerging evidence has shown that long noncoding RNAs (lncRNAs) participate in oncogenesis and tumor progression. We previously found a novel lncRNA p4516 which was closely associated with prognosis by preliminary study of lncRNA expression profile from paired tumors and nontumor tissues in 198 gastric cancer (GC) patients. However, the exact biological functions and the underlying molecular mechanisms of p4516 in gastric tumorigenesis still remain unclear. Materials and methods: The RNA fluorescence in situ hybridization (RNA-FISH) analysis, cytoplasmic and nuclear RNA isolation and qRT-PCR were applied to determine the subcellular localization of p4516. Expression levels of p4516 were assessed using qRT-PCR in both GC cell lines and in 142 primary GC tissues. Correlations between p4516 expression and GC patients' clinicopathological parameters were analyzed. Gain- and loss-of-function experiments were employed to investigate the role of p4516 in proliferation, migration and invasion both in vitro and in vivo. In addition, Western blotting and immunohistochemical staining were used to examine the protein expression levels. Results: LncRNA p4516 was mainly localized in the nucleus of GC cells and p4516 tended to have higher expression levels in GC cells compared to the normal gastric mucosa-derived cells GES-1. Furthermore, higher expression levels of p4516 correlated with worse clinical outcomes in GC patients and acted as an independent prognostic biomarker. Functional analysis revealed that p4516 participated in the regulation of GC cell proliferation, invasion and migration both in vivo and in vitro. Moreover, p4516 was involved in epithelial-mesenchymal transition (EMT) in GC cells. Conclusion: Our study demonstrated the oncogenic role of novel lncRNA p4516 in the gastric carcinogenesis for the first time. High expression of p4516 may act as prognostic marker in patient with gastric cancer.

17.
Cancer Commun (Lond) ; 39(1): 10, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30885279

RESUMO

China is one of the countries with the highest incidence of gastric cancer. There are differences in epidemiological characteristics, clinicopathological features, tumor biological characteristics, treatment patterns, and drug selection between gastric cancer patients from the Eastern and Western countries. Non-Chinese guidelines cannot specifically reflect the diagnosis and treatment characteristics for the Chinese gastric cancer patients. The Chinese Society of Clinical Oncology (CSCO) arranged for a panel of senior experts specializing in all sub-specialties of gastric cancer to compile, discuss, and revise the guidelines on the diagnosis and treatment of gastric cancer based on the findings of evidence-based medicine in China and abroad. By referring to the opinions of industry experts, taking into account of regional differences, giving full consideration to the accessibility of diagnosis and treatment resources, these experts have conducted experts' consensus judgement on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes. This guideline uses tables and is complemented by explanatory and descriptive notes covering the diagnosis, comprehensive treatment, and follow-up visits for gastric cancer.


Assuntos
Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , China , Humanos , Oncologia , Sociedades Médicas
18.
Oncol Lett ; 17(3): 2849-2855, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30854060

RESUMO

In the current era of multi-disciplinary treatment, precise and detailed diagnosis prior to treatment is crucial for clinical practice. For different lesions that fit different indications, the optimum approach for treatment differs significantly. Thus, the recent 8th American Joint Committee on Cancer classification system has introduced 'clinical stage' as a criterion. Endoscopic ultrasonography (EUS) has been the first-line choice for pretreatment staging; however, there is no standardization of the depth classification nor a standard EUS method. Additionally, the accuracy for this diagnostic test has ranged between <40 and 90% in previous studies. The aim of the present study was to determine the accuracy of EUS, identify the discrepancies between EUS and histological results, and analyze the underlying causes. Between June 2014 and February 2016, EUS was performed on gastric carcinoma specimens from 60 consecutive patients. EUS was performed on the resected specimens following surgery, but prior to fixation in formalin, invasion of the gastric wall was determined and the deepest location was marked with sutures. The ultrasound images were independently interpreted, and the quality of the images was scored by two endoscopists. Subsequently, the ultrasound images were compared with the pathological results of the same section. The overall accuracy of EUS was 75%. For locally advanced gastric cancers, EUS had a relatively high accuracy (33/43, 86%). The EUS results corresponded well with the pathological hematoxylin and eosin staining results, and the deepest points determined by EUS were confirmed by pathology in the majority of cases (85%). In total, 50 and 10 cases were scored as having high/moderate and low quality, associated with accuracies of 86% (43/50) and 20% (2/10), respectively. EUS is valuable for pretreatment T-staging, particularly for advanced cases. Proximal stomach cancer exhibited a tendency for improved accuracy. Overall, the results of the present study suggest that standardized scanning processes, particularly including all-encompassing scanning, proper probe-placement and high image quality, lead to improved accuracy of EUS.

19.
Korean J Radiol ; 20(3): 422-428, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30799573

RESUMO

OBJECTIVE: To analyze the detection rate of the inferior pyloric artery (IPA) in patients with gastric cancer by computed tomography arteriography (CTA). MATERIALS AND METHODS: Fifty-four patients (48 males and 6 females; mean age, 59.0 ± 1.5 years) who had undergone radical gastrectomy for gastric cancer from September 2016 to July 2017 at our institution were recruited prospectively. Patients underwent abdominal contrast-enhanced CT scans and CTA imaging reconstruction before the operation. The origin of the IPA in all cases was determined by a radiologist based on CTA images and verified by the surgeon. The accuracy of CTA in diagnosing the origin of the IPA was calculated. Dominant vessels of the origin were analyzed. RESULTS: IPAs were detected by CTA in 51 patients (94.4%). Among these, IPAs originated from the right gastroepiploic artery (RGEA) (24 cases), the gastroduodenal artery (GDA) (4 cases), and the anterior superior pancreaticoduodenal artery (ASPDA) (20 cases). In the remaining 3 cases, the IPAs contained two branches originating from the RGEA and ASPDA, respectively. During surgery, in 2 (3.7%) of the 54 cases of gastric cancer, IPAs could not be detected; the IPAs originated from the RGEA (22 cases), GDA (5 cases), and ASPDA (24 cases). One case had an IPA originating from both the RGEA and the GDA. Finally, the accuracy of CTA in diagnosing the origin artery of the IPA was 85.2% (46/54). CONCLUSION: CTA can detect the origin of the IPA accurately, which can aid surgeons while performing pylorus-preserving operations.


Assuntos
Angiografia , Artéria Gastroepiploica/diagnóstico por imagem , Neoplasias Gástricas/diagnóstico , Angiografia/métodos , Feminino , Gastrectomia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios X
20.
J Cancer ; 10(2): 430-440, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30719137

RESUMO

An oncolytic herpes simplex virus (oHSV) has proven amenable in oncolytic virotherapy and was approved to treat melanoma. The immediate-early (IE) protein ICP27 encoded by gene UL54 is essential for HSV infection. Post-transcriptional modification of UL54 would increase tumor targeting of oHSVs. However, UL54 gene transcription regulatory sequences and factors were not reported yet. Here we isolated a new strain LXMW of type 1 HSV (HSV-1-LXMW) in China and found it's closely related to HSV-1 strains Patton and H129 in the US by the first and next generation DNA sequencing viral DNA phylogenetic analysis. Using a weight matrix-based program Match, we found the UL54 transcription regulatory sequences binding to the transcription factors Oct-1, v-Myb and Pax-6 in HSV-1-LXMW, while the sequences binding to Oct-1 and Hairy in a HSV-2 strain. Further validation showed that HSV-1 and HSV-2 shared the common sequence binding to Oct-1, but had unique sequences to bind v-Myb and Pax-6, or Hairy, respectively, by DNA sequence alignment of total 11 HSV strains. The published results howed that the expression of transcription factors is consistent with the tissue tropism of HSV-1 and HSV-2. In the current article a new HSV-1 strain LXMW was isolated and its putative HSV UL54 transcription regulatory sequences and factors were identified for the first time. Our findings highlight the new understanding of the principles of transcriptional regulation in HSV biology and oncolytic virotherapy.

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