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1.
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.

2.
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.

3.
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.

4.
Surg Endosc ; 2019 Dec 10.
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.

5.
Sci Rep ; 9(1): 15339, 2019 Oct 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.

6.
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
7.
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.

8.
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.

9.
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
10.
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.

11.
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
12.
Cell Death Dis ; 10(2): 33, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30674889

RESUMO

ISL1, a LIM-homeodomain transcription factor, serves as a biomarker of metastasis in multiple tumors. However, the function and underlying mechanisms of ISL1 in gastric cancer (GC) have not been fully elucidated. Here we found that ISL1 was frequently overexpressed in GC FFPE samples (104/196, 53.06%), and associated with worse clinical outcomes. Furthermore, the overexpression of ISL1 and loss-of-function of ISL1 influenced cell proliferation, invasion and migration in vitro and in vivo, including GC patient-derived xenograft models. We used ChIP-seq and RNA-seq to identify that ISL1 influenced the regulation of H3K4 methylation and bound to ZEB1, a key regulator of the epithelial-mesenchymal transition (EMT). Meanwhile, we validated ISL1 as activating ZEB1 promoter through influencing H3K4me3. We confirmed that a complex between ISL1 and SETD7 (a histone H3K4-specific methyltransferase) can directly bind to the ZEB1 promoter to activate its expression in GC cells by immunoprecipitation, mass spectrometry, and ChIP-re-ChIP. Moreover, ZEB1 expression was significantly positively correlated with ISL1 and was positively associated with a worse outcome in primary GC specimens. Our paper uncovers a molecular mechanism of ISL1 promoting metastasis of GC through binding to the ZEB1 promoter together with co-factor SETD7. ISL1 might be a potential prognostic biomarker of GC.

13.
Cancer Manag Res ; 10: 4969-4980, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30464597

RESUMO

Background: Glucose-6-phosphate isomerase (GPI) is a glycolytic-related enzyme that inter-converts glucose-6-phosphate and fructose-6-phosphate in the cytoplasm. This protein is also secreted into the extracellular matrix by cancer cells and is, therefore, also called autocrine motility factor (AMF). Methods: To clarify the roles of AMF/GPI in gastric cancer (GC), we collected 335 GC tissues and the corresponding adjacent noncancerous tissues, performed immunohistochemical studies, and analyzed the relationship between AMF/GPI expression and the patients' clinicopathologic features. Results: AMF/GPI expression was found to be significantly higher in the GC group than in the corresponding noncancerous tissue group (P<0.001). Additionally, AMF/GPI expression positively associated with a higher TNM stage and poorer prognosis in patients. Through Kaplan-Meier analysis and according to the Oncomine database, we found that AMF/GPI was overexpressed in GC tissues compared to normal mucosa, and the patients with higher AMF/GPI expression had poorer outcomes. We used AMF/GPI-silenced GC cell lines to observe how changes in AMP/GPI affect cellular phenotypes. AMF/GPI knockdown suppressed proliferation, migration, invasion, and glycolysis, and induced apoptosis in GC cells. Conclusion: These findings suggest that AMF/GPI overexpression is involved in carcinogenesis and promotes the aggressive phenotypes of GC cells.

14.
BMC Cancer ; 18(1): 811, 2018 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-30103713

RESUMO

BACKGROUND: To investigate the performance of quantitative indicators of MRI in early prediction of the response of gastrointestinal stromal tumor (GIST) to targeted therapy in a patient-based study. METHODS: MRI examinations were performed on 62 patients with GIST using 1.5 T scanners before and at two and 12 weeks after treatment with targeted agents. The longest diameter (LD) and contrast-to-noise ratio (CNR) of the tumors were measured by T2-weighted imaging (T2WI), and the apparent diffusion coefficient (ADC) was determined using diffusion-weighted imaging (DWI). The pre-therapy and early percentage changes (%Δ) of the three parameters were compared with regard to their abilities to differentiate responder and non- responder patients, using ROC curves. RESULTS: There were 42 patients in responder and 20 in non-responder group. After two weeks of therapy, the percentage changes in the ADC and LD were significantly different between the two groups (ADC: responder 30% vs. non- responder 1%, Z = - 4.819, P < 0.001; LD: responder - 7% vs. non- responder - 2%, Z = - 3.238, P = 0.001), but not in T2WI-CNR (responder - 3% vs. non-responder 9%, Z = - 0.663, P = 0.508). The AUCs on ROC for %ΔLD, %ΔT2WI-CNR and %ΔADC after two weeks of therapy were 0.756, 0.552 and 0.881, respectively, for response differentiation. When %ΔADC ≥15% was used to predict responder, the PPV was 93.3%. CONCLUSIONS: The percentage change of the ADC after two weeks of therapy outperformed T2WI-CNR and longest diameter in predicting the early response of GIST to targeted therapy.


Assuntos
Imagem de Difusão por Ressonância Magnética , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Adulto , Idoso , Feminino , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Indóis/administração & dosagem , Indóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Sunitinibe , Resultado do Tratamento
15.
Clin Colorectal Cancer ; 17(2): e307-e313, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29525524

RESUMO

BACKGROUND: The purpose of this study was to retrospectively analyze the pattern and the management of recurrence of rectal cancer treated with 22-fraction intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: This study included patients who underwent IMRT with gross tumor volume of 50.6 Gy in 22 fractions with concurrent capecitabine treatment over a period of 30 days, after which the patients underwent total mesorectal excision at Peking University Cancer Hospital (2007-2015). Study end points were local recurrence-free survival (LRFS), local disease-free survival (LDFS), disease-free survival (DFS), and cancer-specific survival (CSS). RESULTS: A total of 687 patients were included in our analysis. The median age was 57 years (range, 21-87 years), and 66.4% of the patients were male. The estimated 5-year LRFS and 5-year LDFS rates were 94.4% (95% confidence interval [CI], 92.1%-96.7%) and 96.1% (95% CI, 94.1%-98.1%), respectively. The estimated 3-year DFS and 5-year CSS rates were 77.5% (95% CI, 74.1%-80.9%) and 84.7% (95% CI, 80.9%-88.4%), respectively. Overall, 33.3% of patients (9 of 27) who developed local recurrence, 35.8% of patients (19 of 53) who developed lung metastasis, and 60% of patients (15 of 25) who developed liver metastasis received curative treatment after recurrence. The estimated 3-year survival after recurrence rates of patients who received curative versus palliative treatment were significantly different (87.8% vs. 15.3%, P = .000). CONCLUSION: Rectal cancer treated with the 22-fraction IMRT regimen provides good local control. More than one-fourth of patients who develop recurrence have the chance to receive curative treatment with the incorporation of a multidisciplinary team and achieves excellent survival after recurrence.


Assuntos
Adenocarcinoma/radioterapia , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Retais/radioterapia , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Capecitabina/administração & dosagem , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Metástase Neoplásica/terapia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Radioterapia de Intensidade Modulada/métodos , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Adulto Jovem
16.
Cell Physiol Biochem ; 45(4): 1617-1630, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29486473

RESUMO

BACKGROUND/AIMS: Nonalcoholic steatohepatitis includes steatosis along with liver inflammation, hepatocyte injury and fibrosis. In this study, we investigated the protective role and the potential mechanisms of a traditional Chinese medicine ShenFu (SF) preparation in an in vitro hepatic steatosis model. METHODS: In palmitic acid (PA)-induced murine hepatic AML12 cell injury, effects of SF preparation on cellular apoptosis and intracellular triglyceride (iTG) level were assessed using TUNEL and TG Colorimetric Assay. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) levels were measured using DCF and JC-1 assay. Cytokine levels were evaluated using ELISA assay. Immunoblot was used to compare the activation level of c-Jun N terminal kinase (JNK), NADPH oxidase (Nox4), and NFκB pathways. RESULTS: Addition of SF preparation prevented PA-mediated increase of apoptosis and iTG as well as IL-8 and IL-6. In PA-treated cell, SF preparation reduced the level of Nox4 and ROS, while increasing the level of MMP and the expression of manganese superoxide dismutase (MnSOD) and catalase, indicating emendation of mitochondrial dysfunction. Nox4 inhibitor GKT137381 prevented PA-induced increase of ROS and apoptosis, while decreasing iTG slightly and not influencing the level of IL-8 and IL-6. SF preparation prevented PA-induced upregulation of phospho-JNK. JNK inhibitor SP600125 prevented PA-mediated increase of Nox4, IL-8, IL-6 and iTG. Nuclear translocation of NFκB/p65 was detected in PA-treated cells, which was prevented by SF preparation. An IκB degradation inhibitor, BAY11-7082, prevented PA-induced increase of IL-8 and IL-6 as well as iTG, whereas it only decreased ROS levels slightly and showed no influence on cellular apoptosis. CONCLUSION: SF preparation shows a beneficial role in prevention of hepatocyte injury by attenuating oxidative stress and cytokines production at least partially through inhibition of JNK/Nox4 and JNK/NFκB pathway, respectively.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , NADPH Oxidase 4/metabolismo , NF-kappa B/metabolismo , Ácido Palmítico/toxicidade , Transdução de Sinais/efeitos dos fármacos , Animais , Antracenos/farmacologia , Apoptose/efeitos dos fármacos , Catalase/metabolismo , Linhagem Celular , Ensaio de Imunoadsorção Enzimática , Interleucina-6/análise , Interleucina-8/análise , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , NADPH Oxidase 4/antagonistas & inibidores , Pirazóis/farmacologia , Piridinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Fator de Transcrição RelA/metabolismo , Triglicerídeos/análise , Triglicerídeos/metabolismo
17.
Gastric Cancer ; 21(1): 41-54, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28493075

RESUMO

BACKGROUND: We recently reported that miR-1 was one of the most significantly downregulated microRNAs in gastric cancer (GC) patients from The Cancer Genome Atlas microRNA sequencing data. Here we aim to elucidate the role of miR-1 in gastric carcinogenesis. METHODS: We measured miR-1 expression in human GC cell lines and 90 paired primary GC samples, and analyzed the association of its status with clinicopathological features. The effect of miR-1 on GC cells was evaluated by proliferation and migration assay. To identify the target genes of miR-1, bioinformatic analysis and protein array analysis were performed. Moreover, the regulation mechanism of miR-1 with regard to these predicted targets was investigated by quantitative PCR (qPCR), Western blot, ELISA, and endothelial cell tube formation. The putative binding site of miR-1 on target genes was assessed by a reporter assay. RESULTS: Expression of miR-1 was obviously decreased in GC cell lines and primary tissues. Patients with low miR-1 expression had significantly shorter overall survival compared with those with high miR-1 expression (P = 0.0027). Overexpression of miR-1 in GC cells inhibited proliferation, migration, and tube formation of endothelial cells by suppressing expression of vascular endothelial growth factor A (VEGF-A) and endothelin 1 (EDN1). Conversely, inhibition of miR-1 with use of antago-miR-1 caused an increase in expression of VEGF-A and EDN1 in nonmalignant GC cells or low-malignancy GC cells. CONCLUSIONS: MiR-1 acts as a tumor suppressor by inhibiting angiogenesis-related growth factors in human gastric cancer. Downregulated miR-1 not only promotes cellular proliferation and migration of GC cells, but may activates proangiogenesis signaling and stimulates the proliferation and migration of endothelial cells, indicating the possibility of new strategies for GC therapy.


Assuntos
Adenocarcinoma/patologia , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Neovascularização Patológica/genética , Neoplasias Gástricas/patologia , Adenocarcinoma/genética , Adulto , Idoso , Endotelina-1/biossíntese , Feminino , Genes Supressores de Tumor , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/genética , Fator A de Crescimento do Endotélio Vascular/biossíntese
18.
Drug Deliv ; 25(1): 1950-1962, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30799657

RESUMO

Oncolytic herpes simplex viruses (oHSVs) have been approved for clinical usage and become more and more popular for tumor virotherapy. However, there are still many issues for the oHSVs used in clinics and clinical trials. The main issues are the limited anti-tumor effects, intratumor injection, and some side effects. To overcome such challenges, here we review the genetic engineering of the envelope glycoproteins for oHSVs to target tumors specifically, and at the same time we summarize the many neutralization antibodies against the envelope glycoproteins and align the neutralization epitopes with functional domains of the respective glycoproteins for future identification of new functions of the glycoproteins and future engineering of the epitopes to escape from host neutralization.


Assuntos
Glicoproteínas/genética , Neoplasias/terapia , Terapia Viral Oncolítica/métodos , Engenharia de Proteínas/métodos , Simplexvirus/genética , Proteínas do Envelope Viral/genética , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Epitopos/genética , Humanos , Evasão da Resposta Imune/imunologia , Simplexvirus/imunologia
19.
Gastric Cancer ; 21(4): 643-652, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29168120

RESUMO

BACKGROUND: We investigated the superiority of the 8th edition of the tumor-node-metastasis (TNM) system for patients in China with gastric cancer. METHODS: The survival outcomes of 1663 patients with gastric cancer undergoing radical resection were analyzed. RESULTS: In the 8th edition system, homogeneous 5-year survival rates among different pathological TNM (pTNM) categories belonging to the same stage were observed. However, in the 7th edition system, the differences of 5-year survival rate among pTNM categories belonging to the same stage were observed in stages IIB (P = 0.010), IIIB (P = 0.004), and IIIC (P < 0.001). For patients in the pT1-3 (P < 0.001) and pT4a (P < 0.001) categories, there were significant differences in survival between patients in the pN3a and pN3b categories. Furthermore, partial cases (pT4bN0M0/T4aN2M0) of stage IIIB were downstaged to stage IIIA in the 8th edition system, and the 5-year survival rate of these patients was significantly better than that of patients in stage IIIB in the 8th edition system. Similarly, the 5-year survival rate of patients in p4bN2M0/T4aN3aM0 downstaged from stage IIIC to IIIB was significantly better than that of patients in stage IIIC. Compared with the 7th edition system, the 8th edition system had a higher likelihood ratio and linear trend chi-squared score and a smaller Akaike information criteria value. CONCLUSIONS: The 8th edition system is superior to the 7th edition system in terms of homogeneity, discriminatory ability, and monotonicity of gradients for Chinese patients with gastric cancer.


Assuntos
Estadiamento de Neoplasias/métodos , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Análise de Sobrevida , Instituições Filantrópicas de Saúde
20.
World J Gastroenterol ; 23(33): 6172-6180, 2017 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-28970733

RESUMO

AIM: To determine the level of consensus on the definition of colorectal anastomotic leakage (CAL) among Dutch and Chinese colorectal surgeons. METHODS: Dutch and Chinese colorectal surgeons were asked to partake in an online questionnaire. Consensus in the online questionnaire was defined as > 80% agreement between respondents on various statements regarding a general definition of CAL, and regarding clinical and radiological diagnosis of the complication. RESULTS: Fifty-nine Dutch and 202 Chinese dedicated colorectal surgeons participated in the online survey. Consensus was found on only one of the proposed elements of a general definition of CAL in both countries: 'extravasation of contrast medium after rectal enema on a CT scan'. Another two were found relevant according to Dutch surgeons: 'necrosis of the anastomosis found during reoperation', and 'a radiological collection treated with percutaneous drainage'. No consensus was found for all other proposed elements that may be included in a general definition. CONCLUSION: There is no universally accepted definition of CAL in the Netherlands and China. Diagnosis of CAL based on clinical manifestations remains a point of discussion in both countries. Dutch surgeons are more likely to report 'subclinical' leaks as CAL, which partly explains the higher reported Dutch CAL rates.


Assuntos
Fístula Anastomótica/diagnóstico por imagem , Colo/cirurgia , Neoplasias Colorretais/cirurgia , Consenso , Reto/cirurgia , Cirurgiões/psicologia , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/epidemiologia , China/epidemiologia , Meios de Contraste/administração & dosagem , Humanos , Países Baixos/epidemiologia , Radiografia/métodos , Reoperação/estatística & dados numéricos , Inquéritos e Questionários
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