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1.
Gene ; 806: 145922, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34454032

RESUMO

Gastric cancer (GC)-derived cell lines were generally used in basic cancer research and drug screening. However, it is always concerned about the difference between cultured cells and primary tumor by oncologists. To address this question, we compared differentially expressed genes (DEGs) in primary cancers, healthy tissues, and cell lines both in vitro and in silico. Seven reported genes with decreased expression in GCs by DNA methylation were analyzed in our cohort studies and experimentally validation. Selected datasets from TCGA (The Cancer Genome Atlas), CCLE (The Broad Institute Cancer Cell Line Encyclopedia), and GTEx (The Genotype-Tissue Expression project) were used to represent GCs, GC-derived cell lines, and healthy tissues respectively in the in silico analysis. Thirty gastric tissues together with six cell lines were used for validations. Unexpectedly, we experimentally found that reported cancer-related downregulated genes were only found in cancer cell lines but not in biopsies. The unchanged gene expressions in primary GCs were generally consistent with our cohort study, using information from cancerous (TCGA) and healthy tissues (GETx). Substantial differences were also found between DEGs of cancer tissues (TGCA)/ healthy tissues (GTEx) pair and cell lines (CCLE)/ healthy tissues (GTEx) pair, which confirmed the significant differences between primary cancer and cancer cell lines. Moreover, elevated expression of YWHAQ (14-3-3 δ) and THBS1 were observed in the GC biopsies, which might be potential biomarkers for GC diagnosis, considering the increased YWHAQ and THBS1 associated with poor survival rates in gastric cancer patients. In sum, it is suggested that cautions should be taken when using GC cell lines to study genes that show great differences between cell lines and tissues.


Assuntos
Proteínas 14-3-3/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/genética , Neoplasias Gástricas/genética , Trombospondinas/genética , Proteínas 14-3-3/metabolismo , Idoso , Atlas como Assunto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Metilação de DNA , Conjuntos de Dados como Assunto , Epigênese Genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Proteínas de Neoplasias/metabolismo , Cultura Primária de Células , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Trombospondinas/metabolismo , Células Tumorais Cultivadas
2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(4): 571-578, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34494528

RESUMO

Objective To investigate the related factors of pathological complete response(pCR)of patients with gastric cancer treated by neoadjuvant therapy and resection,and to analyze the risk factors of prognosis. Methods The clinical and pathological data of 490 patients with gastric cancer who received neoadjuvant therapy followed by radical gastrectomy from January to December in 2008 were retrospectively analyzed.Univariate and multivariate analyses were performed to identify the risk factors affecting pCR and prognosis. Results Among the 490 patients,41 achieved pCR,and the overall pCR rate was 8.3%(41/490).The pCR rate was 16.0% in the neoadjuvant chemoradiation group and 6.4% in the neoadjuvant chemotherapy group.The results of multivariate analysis showed that neoadjuvant chemoradiation(OR=4.401,95% CI=2.023-9.574,P<0.001)and preoperative therapeutic response as partial response(OR=40.492,95% CI=5.366-305.572,P<0.001)were independent predictors of pCR after neoadjuvant therapy.Multivariate analysis of prognosis showed that poorly differentiated tumor(HR=1.809,95% CI=1.104-2.964,P=0.019),gastric cardia-fundus-body tumor(HR=2.025,95% CI=1.497-2.739,P<0.001),≤15 intraoperative dissected lymph nodes(HR=1.482,95% CI=1.059-2.073,P=0.022),and postoperative complications(HR=1.625,95% CI=1.156-2.285,P=0.005)were independent risk factors for prognosis,while pCR(HR=0.153,95% CI=0.048-0.484,P=0.001)and postoperative adjuvant chemotherapy(HR=0.589,95% CI=0.421-0.823,P<0.001)were independent protective factors of prognosis. Conclusions Patients who achieved pCR after neoadjuvant therapy for locally advanced gastric cancer might have promising long-term survival,and pCR is an independent predictor for overall survival.Compared with chemotherapy alone,preoperative chemoradiotherapy can significantly improve the pCR rate of patients with locally advanced gastric cancer.


Assuntos
Terapia Neoadjuvante , Neoplasias Gástricas , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia
3.
Medicine (Baltimore) ; 100(36): e27017, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516491

RESUMO

RATIONALE: Metastatic gastric cancer patients with poor eastern cooperative oncology group performance status (PS) (≥3) were lack of effective anti-tumor strategies. They always lived with poor PS, severe and multiple symptoms, and usually resulted in extremely limited survival time. Herein, we reported a patient diagnosed with gastric cancer metastasized to multiple bones, along with lymphangitis carcinomatosa in lungs, harboring Her-2 and c-MET amplification with poor PS, positively responded to combinational therapy with trastuzumab and crizotinib. PATIENT CONCERNS: The patient complained of persistent cough and fatigue for 2 months, otherwise, she denied smoking, alcohol history, or any other medical or family history. DIAGNOSIS: With the biopsy results from gastroscopy, as well as computer tomography for chest and abdomen, the patient was diagnosed as gastric adenocarcinoma, with metastasis on lungs, left adrenal gland, retroperitoneal lymph nodes, and multiple bones. INTERVENTIONS: Because of the poor PS (PS = 3), as well as Her-2 and c-MET amplification, the patient received combination treatment with trastuzumab and crizotinib as salvage strategy. OUTCOMES: After 2 months' exposure of trastuzumab and crizotinib, symptoms including persistent cough, and chest distress were alleviated significantly. Simultaneously, chest computer tomography showed significant dissipation of lymphangitis carcinomatosa, as well as apparent reduction of pleural effusion. No adverse reactions including nausea, vomiting, diarrhea, or hypertension was observed during the following 2 months. LESSONS: The present case suggested that combinational therapy with trastuzumab and crizotinib might be effective in metastatic gastric cancer patients harboring Her-2 and c-MET amplification, even with a poor PS. It was also implied that gene sequencing might be valuable, especially in patients with limited treatment strategies.


Assuntos
Adenocarcinoma/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica , Crizotinibe/administração & dosagem , Crizotinibe/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas Proto-Oncogênicas c-met/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Trastuzumab/administração & dosagem , Trastuzumab/uso terapêutico
4.
Medicine (Baltimore) ; 100(36): e27164, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516510

RESUMO

ABSTRACT: Plexiform fibromyxoma (PF) is a rare mesenchymal neoplasm which can be misdiagnosed as the gastrointestinal stromal tumor. This tumor almost formed a lobulated intramural/submucosal mass in the gastric antrum and prepyloric area. It was considered as a benign tumor that exhibited no recurrence, metastasis, or tumor-related mortality. In this study, we reported 2 cases of gastric PF. The first case was a PF patient coexisting with gastric adenocarcinoma. The second case occurred in the gastric upper body close to gastric fundus. They underwent distal gastrectomy and laparoscopic partial gastric resection, respectively. Both of them exhibited a plexiform growth pattern in the submucosa, muscularis propria, and subserosal adipose tissues. The nodules were composed of abundant myxoid or fibromyxoid matrix riching in small thin-walled blood vessels and bland-looking spindle cells. The first case partially showed staggered growth pattern of PF and adenocarcinoma. Immunohistochemically, the spindle cells were diffusely immunoreactive for SMA and vimentin, and focally immunoreactive for CD10. It was important to distinguish the PF from other spindle cell tumors involving the stomach.


Assuntos
Adenocarcinoma/diagnóstico , Fibroma/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Diagnóstico Diferencial , Feminino , Fibroma/complicações , Fibroma/patologia , Fibroma/cirurgia , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Primárias Múltiplas/complicações , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
5.
World J Surg Oncol ; 19(1): 272, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507562

RESUMO

BACKGROUND: To evaluate whether the addition of taxanes to platinum and fluoropyrimidines in adjuvant chemotherapy would result in longer survival than platinum plus fluoropyrimidines in gastric cancer patients who received D2 gastrectomy. METHODS: Data of patients with gastric adenocarcinoma who received D2 gastrectomy and adjuvant chemotherapy with platinum plus fluoropyrimidines or taxanes, platinum plus fluoropyrimidines was retrospectively collected and analyzed. 1:1 Propensity score matching analysis was used to balance baseline characteristics between two groups. Survival curves were estimated using Kaplan-Meier method, and the differences were compared using the log-rank test. RESULTS: Four hundred twenty-five patients in the platinum plus fluoropyrimidines group and 177 patients in the taxanes, platinum plus fluoropyrimidines group were included into analysis. No statistical differences in disease-free survival and overall survival were observed between two groups. After propensity score matching, 172 couples of patients were matched, the baseline characteristics were balanced. The median disease-free survival were 15.8 months (95% CI, 9.3~22.4) in the platinum plus fluoropyrimidines group and 22.6 months (95% CI, 15.9~29.4) in the taxanes, platinum plus fluoropyrimidines group (HR = 0.63; 95% CI, 0.48~0.85; P = 0.002). The median overall survival was 25.4 months for patients in the platinum plus fluoropyrimidines group (95% CI, 19.4~31.3) and 33.8 months (95% CI, 23.5~44.2) for those in the taxanes, platinum plus fluoropyrimidines group (HR = 0.68; 95% CI, 0.53-0.87; log-rank test, P = 0.002). CONCLUSIONS: For gastric adenocarcinoma patients, the adjuvant triplet combination of taxanes, platinum, and fluoropyrimidines regimen after D2 gastrectomy was superior to platinum plus fluoropyrimidines regimen in disease-free survival as well as overall survival. TRIAL REGISTRATION: This project has been registered in the Chinese Clinical Trial Registry ( ChiCTR1800019978 ).


Assuntos
Platina , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Gastrectomia , Humanos , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxoides/uso terapêutico
6.
Zhonghua Zhong Liu Za Zhi ; 43(8): 856-860, 2021 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-34407591

RESUMO

Objective: To evaluate the expression of semaphorin 5B (SEMA5B) in gastric adenocarcinoma and its relationship with prognosis. Methods: In November 2019, the clinicopathological characteristics and SEMA5B mRNA expression data of 341 patients with gastric adenocarcinoma were collected through TCGA database. The relationship between SEMA5B expression in gastric adenocarcinoma tissues and clinical pathologic features and overall survival were analyzed. Gene Set Enrichment Analysis (GSEA) was used to analyze the signaling pathways regulated by SEMA5B. Results: The expression level of SEMA5B mRNA in 341 gastric adenocarcinoma tissues was 0.577±0.587, in adjacent normal tissues was 0.132±0.075, the difference was statistically significant (P<0.001). The median survival time of 109 patients with high expression of SEMA5B mRNA was 14.5 months, 232 patients with low expression of SEMA5B mRNA was 17.9 months (P=0.047). Univariate analysis showed that the expression of SEMA5B mRNA was correlated with histological grade and T stage (P<0.05). The multivariate analysis revealed that age<65 years remained independently associated with overall survival, with a hazard ratio(HR) of 1.042 (95%CI: 1.021-1.064). The multivariate analysis revealed that high expression of SEMA5b mRNA remained independently associated with overall survival, with a HR of 1.195 (95%CI: 0.925-2.551). GSEA showed that malignant tumor signaling pathways (P=0.008), MAPK signaling pathways (P=0.047) and Notch signaling pathways (P=0.029) were differentially enriched in SEMA5B highly expressed phenotype. Conclusions: SEMA5B expression may be a potential prognostic molecular marker for prognosis of GAC patients. Moreover, malignant tumor signaling pathway, MAPK signaling pathway and Notch signaling pathway may be the key pathway regulated by SEMA5B in GAC.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/genética , Adenocarcinoma/patologia , Idoso , Humanos , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
7.
World J Surg Oncol ; 19(1): 259, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34461926

RESUMO

BACKGROUND: The aberrant expression of circular RNAs (circRNAs) plays vital roles in the advancement of human cancers, including gastric cancer (GC). In this study, the functions of circRNA ring finger protein 111 (circ-RNF111) in GC were investigated. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed for the levels of circ-RNF111, microRNA-876-3p (miR-876-3p) and krueppel-like factor 12 (KLF12) mRNA. RNase R assay was conducted for the feature of circ-RNF111. Cell Counting Kit-8 (CCK-8) assay, colony formation assay, wound-healing assay, and transwell assay were applied for cell viability, colony formation, migration, and invasion, respectively. Flow cytometry analysis was used to analyze cell apoptosis and cell cycle process. The glycolysis level was examined using specific commercial kits. Western blot assay was carried out to measure the protein levels of hexokinase 2 (HK-2) and KLF12. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to verify the combination between miR-876-3p and circ-RNF111 or KLF12. Murine xenograft model was constructed for the role of circ-RNF111 in vivo. Immunohistochemistry (IHC) was used for KLF12 level. RESULTS: Circ-RNF111 was higher expressed in GC tissues and cells than normal tissues and cells. Silencing of circ-RNF111 restrained cell viability, colony formation, migration, invasion, cell cycle process and glycolysis and induced apoptosis in GC cells in vitro. Circ-RNF111 positively regulated KLF12 expression via absorbing miR-876-3p. MiR-876-3p downregulation reversed the impacts of circ-RNF111 silencing on GC cell malignant phenotypes. MiR-876-3p overexpression repressed GC cell growth, metastasis and glycolysis, inhibited apoptosis and arrested cell cycle, while KLF12 elevation weakened the effects. Besides, circ-RNF111 knockdown inhibited tumor growth in vivo. CONCLUSION: Circ-RNF111 knockdown relieved the development of GC by regulating miR-876-3p/KLF12 axis.


Assuntos
Fatores de Transcrição Kruppel-Like , MicroRNAs , RNA Circular , Neoplasias Gástricas , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Fatores de Transcrição Kruppel-Like/genética , Camundongos , MicroRNAs/genética , Proteínas Nucleares , Prognóstico , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Ubiquitina-Proteína Ligases
8.
Medicine (Baltimore) ; 100(33): e26951, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414959

RESUMO

ABSTRACT: An overexpression of S-phase kinase-associated protein 2 (SKP2) is frequently observed in human cancer progression and metastasis, and evidence suggests that SKP2 plays a proto-oncogenic role both in vitro and in vivo. However, the function of SKP2 in gastric adenocarcinoma remains largely obscure. We investigated SKP2 expression in human gastric carcinomas.Tissue samples were acquired from 182 cases of gastric adenocarcinoma that were surgically resected from 2006 to 2012. Immunohistochemical staining for SKP2, Beclin-1, and forkhead box protein P3 (FOXP3) was performed. Pearson chi-square test was used to evaluate the associations among clinicopathological variables. The Kaplan-Meier method, the log-rank test, and the Cox proportional-hazards model were used in the analysis of the overall survival (OS) and disease-free survival (DFS).As a result, SKP2 overexpression in gastric adenocarcinomas showed a significant correlation with several favorable clinical factors, including the tumor size, T category, N category, lymphatic invasion, vascular invasion, OS, and DFS. SKP2 expression was positively correlated with the tumoral FOXP3, Beclin-1 expression, and regulatory T cell (Treg) infiltration. The difference in DFS between the SKP2 positive and negative group was attenuated by FOXP3 high expression, Beclin-1 high expression, and Tregs infiltration. Attenuation of the difference in OS by FOXP3 high expression, Beclin-1 high expression, and Tregs infiltration was not significant. In multivariable analysis, SKP2 expression was not correlated with OS and DFS.Our study showed a complex interrelationship between SKP2 and Beclin-1 and FOXP3 expression in gastric adenocarcinoma. The antioncogenic effect of Beclin-1 and FOXP3 expression in gastric adenocarcinoma is related to SKP2 expression.


Assuntos
Adenocarcinoma/metabolismo , Proteína Beclina-1/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Proteínas Quinases Associadas a Fase S/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Análise Serial de Tecidos
9.
Ann Clin Lab Sci ; 51(4): 494-502, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34452887

RESUMO

OBJECTIVE: Gastric cancer is one of the most common gastrointestinal malignancies. miRNAs (microRNAs) have been reported to play a pivotal role in the tumorigenesis of gastric cancer. However, the role of miR-643 in gastric cancer is not fully understood. METHODS: The expression of miR-643 in gastric cancer cell lines was detected by qRT-PCR (quantitative reverse transcription PCR). Cell viability, apoptosis, migration, and invasion were assessed using the Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and wound scratch and Transwell assays, respectively. The target gene of miR-643 was predicted by bioinformatics analysis and validated using luciferase reporter assay. RESULTS: The expression level of miR-643 in gastric cancer cell lines was lower than in the normal gastric epithelium cell line (GES-1). Overexpression of miR-643 inhibited cell viability and colony formation but promoted cell apoptosis in gastric cancer. Transwell invasion assay and in vitro scratch assay evidenced that miR-643 overexpression inhibited gastric cancer cell migration and invasion. Bioinformatics analysis revealed that miR-643 could directly target TXNDC9 (Thioredoxin domain containing 9), and luciferase reporter assay validated this result. Further analysis showed that miR-643 mimics caused a significant reduction of TXNDC9 in gastric cancer cells. Moreover, TXNDC9 overexpression reversed the effects of miR-643 mimics on gastric cancer cell viability, invasion, and migration. CONCLUSION: miR-643 functions as a potential tumor suppressor in gastric cancer by inhibiting cell viability, colony formation, migration, and invasion via targeting TXNDC9, which provides a novel target for the diagnostic treatment of gastric cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Gástricas/patologia , Tiorredoxinas/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Transição Epitelial-Mesenquimal , Humanos , Invasividade Neoplásica , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Tiorredoxinas/genética , Células Tumorais Cultivadas
10.
Medicine (Baltimore) ; 100(34): e27012, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449473

RESUMO

BACKGROUND: Robotic-assisted gastrectomy has been used for treating gastric cancer since 2002. This meta-analysis was conducted to systematically evaluate the efficacy of Da Vinci robotic distal subtotal gastrectomy (RDG) or laparoscopic distal subtotal gastrectomy (LDG) in patients with gastric cancer. METHODS: We conducted searches in domestic and foreign databases, and collected literature in Chinese and English on the efficacy of RDG and LDG for gastric cancer that have been published since the inception of the database. RevMan 5.4.1 was used for meta-analysis and drawing and Stata14.0 was used for publication bias analysis. RESULTS: A total of 3293 patients in 15 studies were included, including 1193 patients in the RDG group and 2100 patients in the LDG groups respectively. The meta-analysis showed that intraoperative blood loss was significantly lower and the number of resected lymph nodes was higher in the RDG group compared to that in the LDG group. In addition, the times to first postoperative food intake and postoperative hospital stay were shortened, and there was a longer length of distal resection margin and prolonged duration of operation. No significant differences were found between the 2 groups with respect to the first postoperative anal exhaust time, length of proximal resection margin, total postoperative complication rate, postoperative anastomotic leakage rate, incidence of postoperative gastric emptying disorder, pancreatic fistula rate, recurrence rate, and mortality rate. CONCLUSION: RDG is a safe and feasible treatment option for gastric cancer, and it is non-inferior or even superior to LDG with respect to therapeutic efficacy and radical treatment.


Assuntos
Gastrectomia/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Neoplasias Gástricas/cirurgia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Ensaios Clínicos como Assunto , Gastrectomia/métodos , Humanos , Laparoscopia/métodos , Tempo de Internação/estatística & dados numéricos , Excisão de Linfonodo , Duração da Cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Gástricas/patologia
11.
Zhonghua Bing Li Xue Za Zhi ; 50(7): 779-784, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34405614

RESUMO

Objective: To investigate the role of tumor budding (TB) in predicting lymph node metastasis of intestinal-type early gastric adenocarcinoma, and to determine the optimal cutoff value of TB number. Methods: A total of 202 patients with intestinal-type early gastric adenocarcinoma, who underwent surgical operation at the Affiliated Wuxi People's Hospital of Nanjing Medical University, Jiangsu, China from 2008 to 2018 were included. According to the International Tumor Budding Consensus Conference (ITBCC) criteria, the number of TB for each case was assessed. The receiver operating characteristic (ROC) curve was employed to determine the optimal cutoff value of TB number for predicting lymph node metastasis, and multivariate logistic regression was used to analyze whether a high TB number was an independent risk factor for lymph node metastasis. In addition, in the patients, who met the indications for endoscopic resection and developed lymph node metastasis, the association of a high number of TB with lymph node metastasis was examined. Results: TBs were observed in 63.4% (128/202) of intestinal-type early gastric adenocarcinomas. Using ROC curve, 4 TBs was found as the optimal cutoff value to predict lymph node metastasis (area under the curve 0.767; sensitivity 0.657; specificity 0.780). Therefore, the 202 cases were divided into two groups: the high-budding (≥4 TBs) group (n=60) and the low-budding (<4 TBs) group (n=142). The high-budding group exhibited a higher rate of lymph node metastasis than that of the low-budding group (41.7% vs 9.1%, P<0.01), and ≥4 TBs was associated with deeper invasion and lymph vessel invasion (P<0.01). The multivariate regression model showed that ≥4 TBs was an independent risk factor for lymph node metastasis (Hazard ratio=8.760, 95%CI 2.648-28.987; P<0.01). Meanwhile, 4 TBs as the cutoff value could better predict lymph node metastasis than the cutoff value advised by the ITBCC. In addition, 3 cases were found to have developed lymph node metastasis even that they met the expanded indications for endoscopic resection, and 2 of these 3 cases exhibited a higher TB number (≥4 TBs). Conclusions: More than 4 TBs are a useful indicator for predicting lymph node metastasis in intestinal-type early gastric adenocarcinoma. It may be used to as an endoscopic resection criterion for patients with a high risk of lymph node metastasis.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
12.
BMC Surg ; 21(1): 320, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372800

RESUMO

AIM: This study was designed to investigate the prognostic effect of preoperative body mass index (BMI) for Type 2 diabetes mellitus (T2DM) patients with non-metastasis gastric cancer (GC) who underwent D2 gastrectomy. METHODS: T2DM patients with pT1-4bN0-3bM0 GC were retrospectively collected in Department of Gastrointestinal Surgical Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital from January, 2000 to December, 2010. These patients underwent D2 radical resection of the stomach combined with regional lymphadenectomy. Chi-square test was used to analyze unordered categorical variables and ranked data, followed by Kaplan-Meier analysis as well as Cox regression models to detect risk factors for survival outcomes. In addition, the cut-off point was determined by the X-tile program. All analyses were carried out using survival package of R and SPSS Software. RESULTS: A total of 302 T2DM patients with pT1-4bN0-3bM0 GC were collected and analyzed. The cut-off points of BMI, identified by the X-tile program, was 19 kg/m2. Patients with low BMI (< 19 kg/m2) had a higher percentage of advanced T stage (T4a and T4b), more advanced TNM stage (stage IIIA, IIIB and IIIC), and more elevated level of serum carcinoembryonic antigen (CEA), compared to those with high BMI (> 19 kg/m2) (all P < 0.05). In the low BMI subgroup, the 5-year overall survival rate was 39.02%, which was as high as 58.11% in the high BMI subgroup (P < 0.05). In the multivariate Cox regression model revealed that IIIC stage (OR = 3.101), N3b stage (OR = 3.113) were the most important prognostic indicators, followed by pretreatment BMI (OR = 2.136). CONCLUSION: Low preoperative BMI (< 19 kg/m2) was a poor prognostic marker for T2DM patients with pT1-4bN0-3bM0 GC.


Assuntos
Diabetes Mellitus Tipo 2 , Neoplasias Gástricas , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Gastrectomia , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
13.
Theranostics ; 11(16): 8112-8128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335983

RESUMO

The coiled-coil domain containing protein members have been well documented for their roles in many diseases including cancers. However, the function of the coiled-coil domain containing 65 (CCDC65) remains unknown in tumorigenesis including gastric cancer. Methods: CCDC65 expression and its correlation with clinical features and prognosis of gastric cancer were analyzed in tissue. The biological role and molecular basis of CCDC65 were performed via in vitro and in vivo assays and a various of experimental methods including co-immunoprecipitation (Co-IP), GST-pull down and ubiquitination analysis et al. Finally, whether metformin affects the pathogenesis of gastric cancer by regulating CCDC65 and its-mediated signaling was investigated. Results: Here, we found that downregulated CCDC65 level was showed as an unfavourable factor in gastric cancer patients. Subsequently, CCDC65 or its domain (a.a. 130-484) was identified as a significant suppressor in GC growth and metastasis in vitro and in vivo. Molecular basis showed that CCDC65 bound to ENO1, an oncogenic factor has been widely reported to promote the tumor pathogenesis, by its domain (a.a. 130-484) and further promoted ubiquitylation and degradation of ENO1 by recruiting E3 ubiquitin ligase FBXW7. The downregulated ENO1 decreased the binding with AKT1 and further inactivated AKT1, which led to the loss of cell proliferation and EMT signal. Finally, we observed that metformin, a new anti-cancer drug, can significantly induce CCDC65 to suppress ENO1-AKT1 complex-mediated cell proliferation and EMT signals and finally suppresses the malignant phenotypes of gastric cancer cells. Conclusion: These results firstly highlight a critical role of CCDC65 in suppressing ENO1-AKT1 pathway to reduce the progression of gastric cancer and reveals a new molecular mechanism for metformin in suppressing gastric cancer. Our present study provides a new insight into the mechanism and therapy for gastric cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Ligação a DNA/metabolismo , Glicoproteínas/metabolismo , Fosfopiruvato Hidratase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , China , Feminino , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor/fisiologia , Glicoproteínas/genética , Humanos , Masculino , Metformina/metabolismo , Metformina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Oncogenes , Prognóstico , Proteínas Proto-Oncogênicas c-akt/fisiologia , Transdução de Sinais/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
14.
Cancer Sci ; 112(9): 3569-3584, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34251747

RESUMO

The abundance and type of immune cells in the tumor microenvironment (TME) significantly influence immunotherapy and tumor progression. However, the role of immune cells in the TME of gastric cancer (GC) is poorly understood. We studied the correlations, proportion, and infiltration of immune and stromal cells in GC tumors. Data analyses showed a significant association of infiltration levels of specific immune cells with the pathological characteristics and clinical outcomes of GC. Furthermore, based on the difference in infiltration levels of immune and stromal cells, GC patients were divided into two categories, those with "immunologically hot" (hot) tumors and those with "immunologically cold" (cold) tumors. The assay for transposase-accessible chromatin using sequencing and RNA sequencing analyses revealed that the hot and cold tumors had altered epigenomic and transcriptional profiles. Claudin-3 (CLDN3) was found to have high expression in the cold tumors and negatively correlated with CD8+ T cells in GC. Overexpression of CLDN3 in GC cells inhibited the expression of MHC-I and CXCL9. Finally, the differentially expressed genes between hot and cold tumors were utilized to generate a prognostic model, which predicted the overall survival of GC as well as patients with immunotherapy. Overall, we undertook a comprehensive analysis of the immune cell infiltration pattern in GC and provided an accurate model for predicting the prognosis of GC patients.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Claudina-3/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Transdução de Sinais/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/metabolismo , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Quimiocina CXCL9/metabolismo , Claudina-3/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , RNA-Seq , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Transcriptoma , Transfecção
15.
Molecules ; 26(13)2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34279414

RESUMO

Malignant tumors have affected the human being since the pharaoh period, but in the last century the incidence of this disease has increased due to a large number of risk factors, including deleterious lifestyle habits (i.e., smoking) and the higher longevity. Many efforts have been spent in the last decades on achieving an early stage diagnosis of cancer, and more effective cures, leading to a decline in age-standardized cancer mortality rates. In the last years, our research groups have developed new metal-based complexes, with the aim to obtain a better selectivity for cancer cells and less side effects than the clinically established reference drug cisplatin. This work is focused on four novel Au(III) and Ru(III) complexes that share the piperidine dithiocarbamato (pipe-DTC) as the ligand, in a different molar ratio. The compounds [AuCl2(pipeDTC)], [Au(pipeDTC)2]Cl, [Ru(pipeDTC)3] and ß-[Ru2(pipeDTC)5] have been synthesized and fully characterized by several chemical analyses. We have then investigated their biological properties in two different cell lines, namely, AGS (gastric adenocarcinoma) and HCT116 (colon carcinomas), showing significant differences among the four compounds. First, the two gold-based compounds and ß-[Ru2(pipeDTC)5] display IC50 in the µM range, significantly lower than cisplatin. Second, we showed that [AuCl2(pipeDTC)] and ß-[Ru2(pipeDTC)5]Cl drive different molecular mechanisms. The first was able to induce the protein level of the DNA damage response factor p53 and the autophagy protein p62, in contrast to the second that induced the ATF4 protein level, but repressed p62 expression. This study highlights that the biological activity of different complexes bringing the same organic ligand depends on the electronic and structural properties of the metal, which are able to fine tune the biological properties, giving us precious information that can help to design more selective anticancer drugs.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células , Complexos de Coordenação/farmacologia , Ouro/química , Rutênio/química , Neoplasias Gástricas/tratamento farmacológico , Tiocarbamatos/química , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Antineoplásicos/química , Complexos de Coordenação/química , Humanos , Neoplasias Gástricas/patologia , Células Tumorais Cultivadas
16.
Genes (Basel) ; 12(6)2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199440

RESUMO

DNA methylation is an important regulator of gene expression that can influence tumor heterogeneity and shows weak and varying expression levels among different genes. Gastric cancer (GC) is a highly heterogeneous cancer of the digestive system with a high mortality rate worldwide. The heterogeneous subtypes of GC lead to different prognoses. In this study, we explored the relationships between DNA methylation and gene expression levels by introducing a sparse low-rank regression model based on a GC dataset with 375 tumor samples and 32 normal samples from The Cancer Genome Atlas database. Differences in the DNA methylation levels and sites were found to be associated with differences in the expressed genes related to GC development. Overall, 29 methylation-driven genes were found to be related to the GC subtypes, and in the prognostic model, we explored five prognoses related to the methylation sites. Finally, based on a low-rank matrix, seven subgroups were identified with different methylation statuses. These specific classifications based on DNA methylation levels may help to account for heterogeneity and aid in personalized treatments.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Neoplasias Gástricas/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Modelos Genéticos , Análise de Regressão , Neoplasias Gástricas/patologia
17.
Cell Death Dis ; 12(7): 696, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34257270

RESUMO

Trastuzumab resistance negatively influences the clinical efficacy of the therapy for human epidermal growth factor receptor 2 (HER2) positive gastric cancer (GC), and the underlying mechanisms remain elusive. Exploring the mechanisms and finding effective approaches to address trastuzumab resistance are of great necessity. Here, we confirmed that endoplasmic reticulum (ER) stress-induced trastuzumab resistance by up-regulating miR-301a-3p in HER2-positive GC cells. Moreover, we elucidated that miR-301a-3p mediated trastuzumab resistance by down-regulating the expression of leucine-rich repeats and immunoglobulin-like domains containing protein 1 (LRIG1) and subsequently activating the expression of insulin-like growth factor 1 receptor (IGF-1R) and fibroblast growth factor receptor 1 (FGFR1) under ER stress. We also found that intercellular transfer of miR-301a-3p by exosomes disseminated trastuzumab resistance. The present study demonstrated that exosomal miR-301a-3p could serve as a non-invasive biomarker for trastuzumab resistance, which was maybe a novel potential therapeutic target to overcome trastuzumab resistance and improve the curative effect of trastuzumab in HER2-positive GC patients.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , MicroRNAs/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Trastuzumab/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Receptor ErbB-2/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Surg Oncol ; 124(5): 780-790, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34227691

RESUMO

BACKGROUND AND OBJECTIVES: The purpose of this study was to compare surgical outcomes before and after implementation of an enhanced recovery protocol (ERP) in gastrectomy for gastric cancer. METHODS: We included patients who underwent open gastrectomy for gastric cancer before (January 2016 to September 2018) or after (October 2018 to September 2020) ERP implementation. The primary outcome was the postoperative length of stay (LOS). Secondary outcomes included 90-day readmission rates and Clavien-Dindo grade ≥ 3 complications. RESULTS: One hundred patients underwent gastrectomy before (pre-ERP group) and 52 underwent gastrectomy after (ERP group) protocol implementation. Demographic and clinicopathologic characteristics were similar. The median (interquartile range) postoperative LOS was shorter in the ERP group (7.0 days [6.0-8.0] vs. 8.0 days [7.0-11.0]; p < 0.001). The ERP group had similar rates of readmission (33% vs. 24%; p = 0.34) and grade ≥ 3 complications (19% vs. 19%; p = 1.0) compared to the pre-ERP group, but experienced lower rates of surgical wound complications (0% vs. 19%; p < 0.001). Rates of other complications were similar. CONCLUSIONS: Implementation of an ERP in patients undergoing open gastrectomy for gastric cancer is feasible and safe and has the potential to decrease postoperative LOS without increasing complication rates.


Assuntos
Recuperação Pós-Cirúrgica Melhorada/normas , Gastrectomia/métodos , Fidelidade a Diretrizes , Implementação de Plano de Saúde , Tempo de Internação/estatística & dados numéricos , Assistência Perioperatória , Neoplasias Gástricas/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia
19.
Am J Gastroenterol ; 116(9): 1859-1867, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34313623

RESUMO

INTRODUCTION: Corpus atrophic gastritis (CAG) is associated with intestinal metaplasia (IM) and pseudopyloric metaplasia (PPM). Prospective data on corpus mucosa PPM and its link to the development of gastric cancer (GC) are lacking. This study aimed to investigate the relationship between the presence of corpus mucosa PPM at baseline and the development of GC at follow-up in patients with CAG. METHODS: A longitudinal cohort study was conducted on patients with consecutive CAG adhering to endoscopic-histological surveillance. Patients were stratified for the presence/absence of corpus PPM without concomitant corpus IM at baseline, and the occurrence of gastric neoplastic lesions at the longest available follow-up was assessed. RESULTS: A total of 292 patients with CAG with a follow-up of 4.2 (3-17) years were included. At baseline, corpus PPM without corpus IM was diagnosed in 62 patients (21.2%). At the follow-up, GC was detected in 5 patients (1.7%) and gastric dysplasia (GD) in 4 patients (1.4%). In all these 9 patients with GC/GD at the follow-up, corpus IM was present at baseline and follow-up. Age <50 years (odds ratio [OR] 2.5), absence of pernicious anemia (OR 4.3), and absence of severe corpus atrophy (OR 2.3) were associated with corpus PPM without corpus IM. DISCUSSION: At the 4.2-year follow-up, in patients with CAG characterized at baseline with corpus PPM without corpus IM, GC or GD was not observed because these lesions were consistently associated with corpus IM. Corpus PPM without corpus IM was associated with younger age, absence of pernicious anemia, and severe corpus atrophy, suggesting a lower stage of disease progression. Corpus PPM alone seems not to be associated with GC, whose development seems to require the presence of corpus IM as a necessary step.


Assuntos
Mucosa Gástrica/patologia , Gastrite Atrófica/complicações , Metaplasia/complicações , Neoplasias Gástricas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Seguimentos , Gastrite Atrófica/patologia , Humanos , Masculino , Metaplasia/patologia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Adulto Jovem
20.
Anticancer Res ; 41(7): 3349-3361, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230131

RESUMO

BACKGROUND/AIM: The present study investigated the oncogenic functions of TACC3 in the progression of gastric cancer (GC). MATERIALS AND METHODS: We analysed TACC3 in relation to cell growth, invasion capability, expression of epithelial-mesenchymal transition (EMT)-related markers, and ERK/Akt/cyclin D1 signaling factors. The correlation between the immunohistochemically confirmed expression of TACC3 and clinical factors was also analyzed. RESULTS: The increased proliferation and invasion of TACC3-over-expressing GC cells was accompanied by altered regulation of EMT-associated markers and activation of ERK/Akt/cyclin D1 signaling. Immunohistochemical analysis of TACC3 in human GC tissues revealed that its expression is correlated with aggressive characteristics and poor prognosis of intestinal-type GC. CONCLUSION: TACC3 contributes to gastric tumorigenesis by promoting EMT via the ERK/Akt/cyclin D1 signaling pathway. The correlation between TACC3 expression and multiple clinicopathological variables implies that its effective therapeutic targeting in GC will depend on the tumor subtype.


Assuntos
Carcinogênese/genética , Ciclina D1/genética , Transição Epitelial-Mesenquimal/genética , Sistema de Sinalização das MAP Quinases/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias Gástricas/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Transdução de Sinais/genética , Estômago/patologia , Neoplasias Gástricas/patologia
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