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2.
N Engl J Med ; 384(13): 1191-1203, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33789008

RESUMO

BACKGROUND: No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer. METHODS: We conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial to evaluate a checkpoint inhibitor as adjuvant therapy in patients with esophageal or gastroesophageal junction cancer. Adults with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by nivolumab at a dose of 480 mg every 4 weeks) or matching placebo. The maximum duration of the trial intervention period was 1 year. The primary end point was disease-free survival. RESULTS: The median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median disease-free survival was 22.4 months (95% confidence interval [CI], 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P<0.001). Disease-free survival favored nivolumab across multiple prespecified subgroups. Grade 3 or 4 adverse events that were considered by the investigators to be related to the active drug or placebo occurred in 71 of 532 patients (13%) in the nivolumab group and 15 of 260 patients (6%) in the placebo group. The trial regimen was discontinued because of adverse events related to the active drug or placebo in 9% of the patients in the nivolumab group and 3% of those in the placebo group. CONCLUSIONS: Among patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, disease-free survival was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 577 ClinicalTrials.gov number, NCT02743494.).


Assuntos
Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Junção Esofagogástrica , Nivolumabe/uso terapêutico , Adenocarcinoma/imunologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Intervalo Livre de Doença , Método Duplo-Cego , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Nivolumabe/efeitos adversos , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/terapia
3.
Medicine (Baltimore) ; 100(10): e24979, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725867

RESUMO

RATIONALE: Advanced signet ring cell (SRC) carcinoma has a worse prognosis. Therefore, early diagnosis and prevention is particularly important; SRC tumors have lower R0 resection rate and are thought to be less chemosensitive than non-SRCC. Consequently, a novel postoperative adjuvant treatment is urgently needed to improve clinical outcomes. PATIENT CONCERNS: A 41-year-old female with advanced gastric SRC carcinoma was treated with radical gastrectomy and oxaliplatin-based regimen for 6 cycles after surgery. She was suspected of recurrence with the high level of carbohydrate antigen (CA) 72-4. DIAGNOSES: The gastroscopy revealed SRC carcinoma of gastric antrum and poorly differentiated adenocarcinoma in some areas. The diagnosis of postoperative pathology report was gastric cancer with stage III C (T4a, N3a, M0). INTERVENTIONS: The level of CA72-4 rapidly increased during the 2 follow-up after the completion of conventional treatment, ex vivo-cultured allogeneic natural killer (NK) cell infusion was offered to prevent recurrence. OUTCOMES: Intravenous injections of NK cells combination with surgical treatment and chemotherapy showed therapeutic effects in this patient with possible relapse. The patient remained disease-free 46 months after the infusion of NK cells until the latest follow-up. LESSONS: CA72-4 appeared to be the most sensitive and specific marker in the gastric cancer patient, and the high level of CA72-4 may indicate the risk of recurrence. This case report provide rationale for NK cell infusion following the rapid increase of CA72-4 to prevent recurrence.


Assuntos
Carcinoma de Células em Anel de Sinete/terapia , Gastrectomia , Células Matadoras Naturais/transplante , Cuidados Pós-Operatórios/métodos , Neoplasias Gástricas/terapia , Adulto , Antígenos Glicosídicos Associados a Tumores/sangue , Antígenos Glicosídicos Associados a Tumores/imunologia , Carcinoma de Células em Anel de Sinete/diagnóstico , Carcinoma de Células em Anel de Sinete/imunologia , Carcinoma de Células em Anel de Sinete/patologia , Terapia Combinada/métodos , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Transplante Homólogo , Resultado do Tratamento
4.
Medicine (Baltimore) ; 100(12): e24697, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761637

RESUMO

RATIONALE: Carcinosarcoma and sarcomatoid carcinoma of the stomach are rare, malignant, and biphasic tumors with high mortality. The differential diagnosis of these 2 diseases remains challenging. In the present study, we present 2 cases of carcinosarcoma and sarcomatoid carcinoma of the stomach. PATIENT CONCERNS: A 54-year-old woman was admitted with complaints of epigastric pain for 4 months, but she became serious for 10 days accompanied by melena. A 75-year-old man was admitted with complaints of epigastric pain for 1 month. DIAGNOSIS: The female had a Borrmann type III irregular ulcerative lesion (5.0 × 4.0 × 1.0 cm) originating from the gastric antrum. The male had Borrmann type I tumor polypoid exophytic (5.0 × 4.0 × 2.0 cm) in the fundus of stomach near the cardia. Both cases were identified as malignant neoplasms by endoscopic biopsy and further confirmed by performing laparoscopic proximal gastrectomy, esophagogastrostomy, and palliative distal subtotal gastrectomy. The postoperative histopathological morphology and immunohistochemistry studies revealed sarcomatoid carcinoma for the female and gastric carcinosarcoma for the male respectively. INTERVENTIONS: The female patient subsequently underwent laparoscopy-assisted radical distal gastrectomy for gastric cancer followed by systemic chemotherapy with oxaliplatin plus tegafur. The male patient underwent laparoscopic proximal gastrectomy and esophagogastrostomy were performed. OUTCOMES: The female had a mixture of a little poorly-differentiated adenocarcinoma and abundant sarcomatoid spindle cell elements, and is still alive healthy up to date for 2 and a half years after surgery by phone follow-up. The male patient had both adenocarcinoma and fibrosarcoma in a single tumor, and died 1 month after the operation. LESSONS: The present study provides insight into the clinical findings, differential diagnosis, and prognosis of carcinosarcomas and sarcomatoid carcinomas of the stomach. More cases are needed for further studies in the future.


Assuntos
Carcinoma/diagnóstico , Carcinossarcoma/diagnóstico , Neoplasias Gástricas/diagnóstico , Dor Abdominal/etiologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/complicações , Carcinoma/patologia , Carcinoma/terapia , Carcinossarcoma/complicações , Carcinossarcoma/patologia , Carcinossarcoma/terapia , Quimioterapia Adjuvante , Diagnóstico Diferencial , Evolução Fatal , Feminino , Gastrectomia , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Gastroscopia , Humanos , Biópsia Guiada por Imagem , Laparoscopia , Masculino , Melena/etiologia , Pessoa de Meia-Idade , Oxaliplatina/uso terapêutico , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Tegafur/uso terapêutico , Resultado do Tratamento
5.
BMC Cancer ; 21(1): 216, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653317

RESUMO

BACKGROUND: HIPEC is an emerging procedure to treat peritoneal metastasis of gastric cancer. Data about HIPEC in locally advanced gastric cancer is scarce. The purpose of this trial is to evaluate the safety and toxicity of prophylactic HIPEC with cisplatin for patients with locally advanced gastric cancer. METHODS: From March 2015 to November 2016, a prospective, randomized phase II trial was conducted. After radical gastrectomy, patients in the experimental group underwent HIPEC with cisplatin followed by adjuvant chemotherapy with SOX regime. Patients in the other group were treated with SOX regime alone. Postoperative complications and patient survival were compared. RESULTS: In total, 50 patients were eligible for analyses. No significant difference was found in the incidence of postoperative complications including anastomotic/intestinal leakage, liver dysfunction, bone marrow suppression, wound infection and ileus (P > 0.05). Mean duration of hospitalization after radical gastrectomy was 11.7 days. 12.2 days in experimental group and 10.8 days in control group respectively (P = 0.255). The percentage of patients with elevated tumor markers was 12.1% in experimental group, which was significantly lower than 41.2% in control group (P = 0.02). 3-year RFS of patients who treated with or without prophylactic HIPEC were 84.8 and 88.2% respectively (P = 0.986). In the multivariate analysis, pathological T stage was the only independent risk factor for the RFS of patients (P = 0.012, HR =15.071). CONCLUSION: Additional intraoperative HIPEC with cisplatin did not increase postoperative complications for locally advanced gastric cancer after curative surgery. Prophylactic HIPEC with cisplatin was safe and tolerable, while it did not reduce the risk of peritoneal recurrence in this trial, supporting further studies to validate the efficacy of it. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000038331. Registered 18 September 2020 - Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=59692 .


Assuntos
Gastrectomia , Neoplasias Gástricas/terapia , Idoso , Idoso de 80 Anos ou mais , Cisplatino/administração & dosagem , Terapia Combinada , Feminino , Gastrectomia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Prospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
6.
Mol Med Rep ; 23(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33537819

RESUMO

Hyperthermia is one of the most widely employed adjuvant treatments for cancer, especially for hyperthermic intraperitoneal chemotherapy, and has few side effects. Gastric cancer has various hyperthermia sensitivities, but the exact molecular mechanisms remain to be elucidated. In the present study, western blotting was performed to detect differential expression of proteins that have been reported to be upregulated in gastric cancer. Following knockdown of these proteins, apoptosis was measured by Annexin V­FITC/propidium iodide (PI) double staining and hyperthermia treatment was applied. To evaluate the effect of cyclin­dependent kinase 6 (CDK6) on hyperthermia­induced apoptosis, CDK6 was knocked down or inhibited by the addition of a specific inhibitor and subsequent PI staining and cell proliferation, migration and invasion assays were performed. Hyperthermia­induced protein kinase B (AKT) expression and phosphorylation inhibition were detected. As demonstrated in the present study, the hyperthermia­induced proteins kinesin family member 11 (KIF11), cyclin­dependent kinase 6 (CDK6), stromal antigen 2, NIMA­related kinase 2 and karyopherin subunit α 4 were highly expressed in gastric cancer cells, including SH­10­TC and HGC­27 cells. Knockdown of KIF11 significantly increased apoptosis without hyperthermia treatment and CDK6 significantly increased hyperthermia­induced apoptosis, prompting the present study to focus on CDK6. It was further confirmed that CDK6 activity was critical for decreasing hyperthermia­induced apoptosis and for cell proliferation. Hyperthermia­induced AKT expression and phosphorylation inhibition is potentially the main cause of CDK6 transcriptional upregulation. Taken together, these findings demonstrated that CDK6 is upregulated via hyperthermia­induced AKT inhibition and subsequently protected gastric cancer cells from hyperthermia­induced apoptosis, indicating that it is a potential therapeutic target to sensitize gastric cancer cells to hyperthermia­based therapy.


Assuntos
Quinase 6 Dependente de Ciclina/biossíntese , Regulação Neoplásica da Expressão Gênica , Hipertermia Induzida , Proteínas de Neoplasias/biossíntese , Neoplasias Gástricas/metabolismo , Transcrição Genética , Regulação para Cima , Linhagem Celular Tumoral , Quinase 6 Dependente de Ciclina/genética , Humanos , Proteínas de Neoplasias/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia
7.
Nat Commun ; 12(1): 975, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579944

RESUMO

Although tumor genomic profiling has identified small subsets of gastric cancer (GC) patients with clinical benefit from anti-PD-1 treatment, not all responses can be explained by tumor sequencing alone. We investigate epigenetic elements responsible for the differential response to anti-PD-1 therapy by quantitatively assessing the genome-wide chromatin accessibility of circulating CD8+ T cells in patients' peripheral blood. Using an assay for transposase-accessible chromatin using sequencing (ATAC-seq), we identify unique open regions of chromatin that significantly distinguish anti-PD-1 therapy responders from non-responders. GC patients with high chromatin openness of circulating CD8+ T cells are significantly enriched in the responder group. Concordantly, patients with high chromatin openness at specific genomic positions of their circulating CD8+ T cells demonstrate significantly better survival than those with closed chromatin. Here we reveal that epigenetic characteristics of baseline CD8+ T cells can be used to identify metastatic GC patients who may benefit from anti-PD-1 therapy.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Cromatina , Receptor de Morte Celular Programada 1/genética , Neoplasias Gástricas/genética , Biomarcadores Tumorais , Proliferação de Células , Sequenciamento de Cromatina por Imunoprecipitação , Genoma , Humanos , Receptor de Morte Celular Programada 1/imunologia , Alinhamento de Sequência , Análise de Sequência de DNA , Neoplasias Gástricas/terapia , Transposases/genética
8.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(1): 23-26, 2021 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-33461248

RESUMO

Gastric cancer is a common type of malignant tumors, but its clinical prognosis remains unsatisfactory. Up to 2020, a growing number of high-quality clinical researches has provided reliable evidence for clinical practice. Evidences from surgery, perioperative treatment and immunotherapy, such as changes in surgical methods, improvement of perioperative chemotherapy and combination of immune and chemotherapy strategy, provided the possibility to improve the clinical efficacy of gastric cancer. In our clinical practice, gastrointestinal surgeons need to integrate the current research progression and develop individualized strategy for different patients, which is expected to further improve the prognosis and quality of life for patients with gastric cancer.


Assuntos
Neoplasias Gástricas , Pesquisa Biomédica/tendências , Terapia Combinada , Gastrectomia , Humanos , Prognóstico , Qualidade de Vida , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/terapia
9.
Medicine (Baltimore) ; 100(2): e24249, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33466209

RESUMO

BACKGROUND: Gastric cancer is one of the most common malignant tumors, which seriously affect peoples quality of life and threaten people's health. Precancerous lesions of gastric cancer (PLGC) are a critical stage in the occurrence and development of gastric cancer. Early effective intervention is an important means to prevent and control gastric cancer. In this study, we will evaluate the efficacy and safety of complementary and alternative therapies in the treatment of PLGC by Bayesian network meta-analysis (NMA). METHODS: We will search PubMed, Cochrane Library, CNKI and other databases to gather randomized controlled trials (RCTs) on the treatment of PLGC with complementary and alternative therapies. Two reviewers will screen the literature and extract the data according to the inclusion and exclusion criteria, and then assess the quality and bias risk according to Cochrane's Risk of Bias Assessment Tool. Bayesian network meta-analysis will be conducted by Stata16.0 and WinBUGS1.4.3. RESULTS: This study will compare and rank the efficacy and safety of different complementary and alternative therapies for PLGC. CONCLUSION: This study can provide reliable evidence for the efficacy and safety of complementary and alternative therapies in treatment of PLGC. We expect to provide scientific and rigorous evidence support for clinicians and patients, and then assist them to choose the optimum treatment. PROTOCOL REGISTRATION NUMBER: INPLASY2020120077.


Assuntos
Terapias Complementares/métodos , Lesões Pré-Cancerosas/terapia , Neoplasias Gástricas/terapia , Teorema de Bayes , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Neoplasias Gástricas/patologia , Resultado do Tratamento
10.
J Surg Oncol ; 123(4): 911-922, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33400838

RESUMO

BACKGROUND AND OBJECTIVES: We sought to evaluate the impact of lymphovascular invasion (LVI) and perineural invasion (PNI) on survival outcomes in gastric cancer patients treated with preoperative therapy. METHODS: Patients with gastric cancer treated with preoperative therapy and potentially curative resection were stratified according to the presence of LVI, PNI, or both. Kaplan-Meier and Cox regression analyses were used to evaluate the impact on overall survival (OS) and disease-free survival (DFS). RESULTS: The study included 281 patients, of whom 93 (33%) had LVI, 69 (25%) had PNI, 51 (18%) had both LVI and PNI, and 170 (61%) had neither. LVI and PNI were each associated with higher ypT and ypN categories and more positive lymph nodes (all p < .001), associations that were emphasized with both factors present. On multivariable analyses, ypN (p < .001) and concurrent LVI/PNI (hazard ratio [HR]: 2.62; 95% confidence interval [CI]: 1.55-4.45; p = .001) were predictive of OS and DFS (ypN: p < .001; both LVI/PNI: HR: 2.27; 95% CI: 1.34-3.82; p = .002). CONCLUSIONS: Gastric cancer patients with concurrent LVI and PNI after preoperative therapy have more advanced disease and worse survival outcomes than patients with neither or only one of these factors.


Assuntos
Adenocarcinoma/mortalidade , Quimiorradioterapia/mortalidade , Linfonodos/patologia , Terapia Neoadjuvante/mortalidade , Períneo/patologia , Cuidados Pré-Operatórios , Neoplasias Gástricas/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Taxa de Sobrevida
11.
J Surg Oncol ; 123(4): 904-910, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33428786

RESUMO

INTRODUCTION: The PERISCOPE I (Treatment of PERItoneal dissemination in Stomach Cancer patients with cytOreductive surgery and hyPErthermic intraperitoneal chemotherapy) study was conducted to investigate the safety and feasibility of hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients with limited peritoneal dissemination. In this study, tumor characteristics and clinical outcome of the patients treated in the PERISCOPE I trial were investigated. METHODS: Patients who had undergone the full study protocol were selected; that is, preoperative systemic chemotherapy, followed by a surgical procedure consisting of a (sub)total gastrectomy, cytoreductive surgery, and HIPEC with oxaliplatin (460 mg/m2 ) and docetaxel (in escalating doses). RESULTS: Twenty-five PERISCOPE I patients underwent the full study protocol. Most patients had an ypT3-4 tumor (96%) and the diffuse-type histology was predominant (64%). Seven patients (28%) had a microscopically irradical (R1) resection. In all patients, a complete cytoreduction was achieved. Median follow-up was 37 (95% confidence interval [CI]: 34-39) months. Disease recurrence was detected in 17 patients (68%). Median disease-free and overall survival were 12 and 15 months, respectively. CONCLUSION: In this series of gastric cancer patients with limited peritoneal dissemination who underwent HIPEC surgery, unfavorable tumor characteristics were common. Survival might be encouraging but disease recurrence was frequent. The efficacy of an HIPEC procedure in improving prognosis is currently being investigated in the PERISCOPE II trial.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução/mortalidade , Hipertermia Induzida/mortalidade , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Adulto , Idoso , Terapia Combinada , Docetaxel/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/terapia , Prognóstico , Neoplasias Gástricas/terapia , Taxa de Sobrevida
12.
J Surg Oncol ; 123(4): 923-931, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33497471

RESUMO

BACKGROUND AND OBJECTIVE: Perioperative chemotherapy (PC) with radical surgery represents the gold standard of treatment for resectable advanced gastric cancer (GC). The prognostic value of pathological tumor regression grade (TRG) induced by neoadjuvant chemotherapy (NACT) is not clearly established. This study aimed to investigate the correlation between TRG and survival in GC. METHODS: Patients affected by advanced GC undergoing PC and radical surgery were considered. TRG was assessed for each patient according to Becker's grading system. The correlation between TRG and survival was investigated. RESULTS: One-hundred patients were selected; 25 showed a good response (GR) (TRG 1a/1b), while 75 had a poor response (PR) (TRG 2/3) to NACT. GR patients showed better disease-free survival (DFS) (52 vs. 19 months, p < .001) and disease-specific survival (DSS) (57 vs. 25 months, p < .0001) when compared to PR patients. On univariate analysis, TRG, lymph node ratio (LNR), tumor size, grading, and post-neoadjuvant therapy TNM stage were significantly correlated with survival. On multivariate analysis, TRG, LNR and tumor size were independent prognostic factors for DFS and DSS. CONCLUSIONS: TRG, LNR, and tumor size are independent prognostic factors for DFS and DSS in patients with advanced GC undergoing NACT.


Assuntos
Adenocarcinoma/patologia , Quimioterapia Adjuvante/mortalidade , Terapia Neoadjuvante/mortalidade , Neoplasias Gástricas/patologia , Adenocarcinoma/terapia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Neoplasias Gástricas/terapia , Taxa de Sobrevida , Resultado do Tratamento
13.
Anticancer Res ; 41(2): 609-617, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517265

RESUMO

BACKGROUND/AIM: Disease recurrence is frequently observed after curative resection of advanced gastric cancer resulting in a poor prognosis. In the present study, we identified a candidate biomarker to predict recurrence and prognosis after curative resection of gastric cancer. MATERIALS AND METHODS: A transcriptome analysis was conducted using surgically resected cancerous tissue from patients with metastatic gastric cancer to identify genes that are upregulated in primary and metastatic tissues. RESULTS: Ring finger protein, transmembrane 2 (RNFT2) mRNA expression was upregulated in primary gastric cancer tissues and metastases compared with non-cancerous tissues. RNFT2 expression in gastric cancer cell lines was positively correlated with the EMT-related molecules GSC, MMP9, and RAC1. The RNFT2 high expression group exhibited a significantly shorter postoperative overall survival. Peritoneal recurrence was significantly higher in the RNFT2 high expression group. CONCLUSION: RNFT2 mRNA expression predicts peritoneal recurrence and is a potential prognostic biomarker for gastric cancer following curative gastrectomy.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias Peritoneais/metabolismo , Neoplasias Gástricas/metabolismo , Idoso , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Transição Epitelial-Mesenquimal , Feminino , Gastrectomia , Humanos , Masculino , Proteínas de Membrana/genética , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
14.
Cancer Sci ; 112(3): 1026-1037, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33404124

RESUMO

The function of ANO9 in gastrointestinal cancer remains unclear. We investigated the biological behaviors and clinical prognostic values of ANO9 in gastric cancer (GC). Knockdown experiments were performed on human GC cell lines using ANO9 siRNA. Eighty-four primary tissue samples from patients with advanced GC were examined immunohistochemically (IHC). Knockdown of ANO9 reduced the progression of cancer cells in MKN7 and MKN74 cells. A microarray analysis revealed that ANO9 regulated PD-L2 via interferon (IFN)-related genes. We confirmed using flow cytometry that the depletion of ANO9 reduced the binding ability to PD-1 by downregulating the expression of PD-L2 in MKN7 and MKN74 cells. IHC revealed a correlation between the expression of ANO9 and PD-L2 and also that the strong expression of ANO9 was an independent poor prognostic factor in patients with advanced GC. The present results indicate that ANO9 regulates PD-L2 and binding ability to PD-1 via IFN-related genes in GC. Therefore, ANO9 has potential as a biomarker and target of immune checkpoint blockage (ICB) for GC.


Assuntos
Anoctaminas/metabolismo , Biomarcadores Tumorais/metabolismo , Proteínas de Transferência de Fosfolipídeos/metabolismo , Proteína 2 Ligante de Morte Celular Programada 1/genética , Neoplasias Gástricas/genética , Idoso , Anoctaminas/antagonistas & inibidores , Anoctaminas/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Apoptose/imunologia , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Feminino , Seguimentos , Gastrectomia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , /uso terapêutico , Interferons/metabolismo , Masculino , Proteínas de Transferência de Fosfolipídeos/antagonistas & inibidores , Proteínas de Transferência de Fosfolipídeos/genética , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo , Estômago/patologia , Estômago/cirurgia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Taxa de Sobrevida
15.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(2): 119-124, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33504417

RESUMO

Objective To explore whether oncolytic adenovirus expressing CCL19 can inhibit the growth of gastric cancer cells and activate anti-tumor immune response. Methods Mouse CCL19 gene was inserted into the E3 region of oncolytic adenovirus Ad5 to obtain engineered oncolytic adenovirus Ad5-CCL19. The expression of CCL19 in Ad5-CCL19-infected mouse MFC cells was detected by Western blotting. The effects of Ad5-CCL19 on the proliferation of MFC cells, MGC803 cells and BGC823 cells were tested by MTT assay. The anti-tumor activity of Ad5-CCL19 in vivo was examined by MFC cell subcutaneous transplantation tumor model. Immunofluorescence histochemical staining was used to detect CD4 and CD8 expression in tumor tissue. The secretion levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in tumor infiltrating T cells were detected by flow cytometry. Results Ad5-CCL19 could effectively infect MFC cells to secrete CCL19. Also, Ad5-CCL19 could induce significant dose-dependent cytotoxicity against target cells in vitro. The experiment in vivo showed that Ad5-CCL19 had stronger inhibitory effects on MFC cell tumor than Ad5 in the mice, and it could effectively enhance the infiltration of CD4+ T cells and CD8+ T cells and increase the secretion of IFN-γ and TNF-α in tumor tissues. Conclusion Ad5-CCL19 can significantly infect MFC gastric cancer cells to inhibit their growth and improve the anti-tumor immune activity of the tumor site.


Assuntos
Terapia Viral Oncolítica , Neoplasias Gástricas , Adenoviridae/genética , Animais , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Quimiocina CCL19 , Imunidade , Camundongos , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia
16.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(2): 101-106, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33508913

RESUMO

Local advanced gastric cancer (LAGC) accounts for a large proportion of annual newly diagnosed gastric cancer patients in China. There is a general consensus for D2 radical gastrectomy followed by postoperative adjuvant chemotherapy for LAGC patients, and this therapeutic strategy has been confirmed by a series of clinical trials to obviously improve the patients' prognosis; however, the recurrence rate is still high (about 50%-80% in advanced stage), which makes it difficult to further improve the long-term survival. Perioperative therapy, especially whether preoperative neoadjuvant therapy (NAT) can improve the efficacy of patients with LAGC, has been paid more and more attention. NAT is mainly defined as a preoperative chemotherapy or chemoradiotherapy, aiming at increasing curative resection rate by downstaging tumor, eliminating micrometastases, and autologously testing of anti-cancer drug sensitivity etc. However, there are still some controversy whether LAGC patients could gain survival benefit from NAT and also lack of general consensus for this issue. In this paper, the author reviews and analyzes the current situation of perioperative therapies for LAGC patients, especially emphasize the results of neoadjuvant chemotherapy or chemoradiotherapy reported by various high-level clinical studies. The preliminary effect of perioperative chemotherapy combined with molecular targeted or immunotherapy has also aroused great interest and attention. While we continue to carry out NAT and look forward to more new high-level evidence trials on NAT, we must emphasize again that R0 gastrectomy remains the most important therapeutic modality for the patients with LAGC.


Assuntos
Gastrectomia/métodos , Assistência Perioperatória , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Quimioterapia Adjuvante , Terapia Combinada , Humanos , Excisão de Linfonodo , Terapia Neoadjuvante , Estadiamento de Neoplasias , Assistência Perioperatória/tendências , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/terapia
17.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(2): 112-117, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33508915

RESUMO

Perioperative treatment is critical to improve the outcomes of patients with advanced gastric cancer. There are three therapeutic modes of perioperative treatment for resectable gastric cancer: neoadjuvant chemotherapy+ D1/D2 surgery+ adjuvant chemotherapy, D0/D1 surgery+ adjuvant radiochemotherapy, and D2 surgery+ adjuvant chemotherapy. Over the decades, a large number of clinical studies had been conducted to optimize the perioperative treatment mode of gastric cancer, including the postoperative radiotherapy and chemotherapy, and perioperative chemotherapy, and to explore the feasibility of preoperative radiochemotherapy, targeted therapy, and immunotherapy in advanced gastric cancer. After nearly 20 years of development and exploration, although the perioperative treatment mode for advanced gastric cancer has become standardized, there are still some core issues that need to be solved urgently, including the selection of population for perioperative treatment, the limitation of efficaly evaluation criteria, insufficient emphasis on laparoscopic exploration before neoadjuvant treatment, and lack of exploration in esophagogastric junction cancer. We should fully integrate the current clinical research data into clinical practice, adopt a multidisciplinary diagnosis and treatment mode, and follow the principles of standardized diagnosis and treatment based on a multi-dimensional analysis of patient characteristics, and formulate the most reasonable treatment strategy to ultimately benefit patients.


Assuntos
Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Terapia Combinada , Junção Esofagogástrica , Gastrectomia , Humanos , Excisão de Linfonodo , Terapia Neoadjuvante , Assistência Perioperatória , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/terapia
18.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(2): 118-121, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33508916

RESUMO

Enhanced recovery after surgery (ERAS) has deeply influenced the clinical practice of surgery, anesthesia and nursing since its inception in 1997. The successful implementation of perioperative ERAS in gastric cancer depends on continually boosting the awareness and acceptance of ERAS among medical staff, carrying out multidisciplinary collaboration, improving patients' compliance and combining key items to the clinical pathways. Future efforts should be made to explore the most appropriate implementation strategy of perioperative ERAS in gastric cancer.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Neoplasias Gástricas , Procedimentos Clínicos , Humanos , Assistência Perioperatória , Complicações Pós-Operatórias/prevenção & controle , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/terapia
19.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(2): 128-137, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33508918

RESUMO

Objective: To investigate the effectiveness, safety, and prognosis of neoadjuvant chemoradiotherapy (nCRT) for Siewert type II and III adenocarcinomas of the esophagogastric junction (AEG). Methods: This study is a prospective randomized controlled clinical study (NCT01962246). AEG patients who were treated at the Third Department of Surgery of the Fourth Hospital of Hebei Medical University from February 2012 to June 2016 were included. All of the enrolled patients were diagnosed with type II or III locally advanced AEG gastric cancer (T2-4N0-3M0 or T1N1-3M0) by gastroscopy and CT before operation; the longitudinal axis of the lesion was ≤ 8 cm; no anti-tumor treatment was previously given and no contraindications of chemotherapy and surgery were found. Case exclusion criteria: serious diseases accompanied by liver and kidney, cardiovascular system and other vital organs; allergy to capecitabine or oxaliplatin drugs or excipients; receiving any form of chemotherapy or other research drugs; pregnant or lactating women; patients with diseases resulting in difficulty to take capecitabine or with concurrent tumors. Based on sample size estimation, a total of 150 AEG patients were enrolled. Using the random number table method, the enrolled patients were divided into the nCRT group and the direct operation group with 75 cases in each group. The nCRT group received XELOX chemotherapy (capecitabine+ oxaliplatin) before surgery and concurrent radiotherapy (45 Gy, 25 times, 1.8 Gy/d, 5 times/week). Clinical efficacy of the nCRT group was evaluated by the solid tumor efficacy evaluation standard (RECIST1.1) and the tumor volume reduction rate was measured on CT. After completing the preoperative examination in the direct operation group, and 8-10 weeks after the end of nCRT in the nCRT group, surgery was performed. Laparoscopic exploration was initially performed. According to the Japanese "Regulations for the Treatment of Gastric Cancer", a transabdominal radical total gastrectomy combined with perigastric lymph node dissection was performed. The primary outcome was the 3-year overall survival (OS) and disease-free survival rate (DFS); the secondary outcomes were R0 resection rate, the toxicity of chemotherapy, and surgical complications. The follow-up ended on December 31, 2019. The postoperative recurrence, metastasis and survival time of the two groups were collected. Results: After excluding patients with incomplete clinical data, patients or family members requesting to withdraw informed consent, and those failing to follow the treatment plan, 63 cases in the nCRT group and 69 cases in the direct operation group were finally enrolled in the study. There were no statistically significant differences in baseline characteristics of the two groups (all P>0.05). Sixty-three patients in the nCRT group were evaluated by RECIST1.1 after treatment, the image based effective rate was 42.9% (27/63), and the stable disease rate was 98.4% (62/63); the tumor volume before and after nCRT measured on CT was (58.8±24.4) cm(3) and (46.6±25.7) cm(3), respectively, the effective rate of tumor volume reduction measured by CT was 47.6% (30/63). Incidences of neutrophilopenia [65.1% (41/63) vs. 40.6% (28/69), χ(2)=7.923, P=0.005], nausea [81.0% (51/63) vs. 56.5% (39/69), χ(2)=9.060, P=0.003] and fatigue [74.6% (47/63) vs. 42.0% (29/69), χ(2)=14.306, P=0.001] in the nCRT group were significantly higher than those in the direct surgery group. Radiation gastritis/esophagitis and radiation pneumonia were unique adverse reactions in the nCRT group, with incidences of 52.4% (33/63) and 15.9%(10/63), respectively. The classification of tumor regression of 63 patients in nCRT group presented as 11 cases of grade 0 (17.5%), 20 cases of grade 1 (31.7%), 28 cases of grade 2 (44.4%), and 5 cases of grade 3 (7.9%). Eleven (17.5%) patients achieved pathologic complete response. Sixty-one (96.8%) patients in the nCRT group underwent R0 resection, which was higher than 87.0% (60/69) in the direct surgery group (χ(2)=4.199, P=0.040). The mean number of harvested lymph nodes in the specimens in the nCRT group and the direct operation group was 27.6±12.4 and 26.8±14.6, respectively, and the difference was not statistically significant (t=-0.015, P=0.976). The pathological lymph node metastasis rate and lymph node ratio in the two groups were 44.4% (28/63) vs. 76.8% (53/69), and 4.0% (70/1 739) vs. 21.9% (404/1 847), respectively with statistically significant differences (χ(2)=14.552, P<0.001, and χ(2)=248.736, P<0.001, respectively). During a median follow-up of 52 (27-77) months, the 3-year DFS rate in the nCRT group and the direct surgery group was 52.4% and 39.1% (P=0.049), and the 3-year OS rate was 63.4% and 52.2% (P=0.019), respectively. According to whether the tumor volume reduction rate measured by CT was ≥ 12.5%, 63 patients in the nCRT group were divided into the effective group (n=30) and the ineffective group (n=33). The 3-year DFS rate of these two subgracps was 56.6% and 45.5%, respectively without significant difference (P=0.098). The 3-year OS rate was 73.3% and 51.5%,respectively with significant difference (P=0.038). The 3-year DFS rate of patients with the tumor regression grades 0, 1, 2 and 3 was 81.8%, 70.0%, 44.4%, and 20.0%, repectively (P=0.024); the 3-year OS rate was 81.8%, 75.0%, 48.1% and 40.0%, repectively (P=0.048). Conclusion: nCRT improves treatment efficacy of Siewert type II and III AEG patients, and the long-term prognosis is good.


Assuntos
Adenocarcinoma , Quimiorradioterapia Adjuvante , Junção Esofagogástrica , Terapia Neoadjuvante , Neoplasias Gástricas , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/administração & dosagem , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Gastrectomia , Humanos , Excisão de Linfonodo , Estadiamento de Neoplasias , Oxaliplatina/administração & dosagem , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia
20.
Expert Opin Drug Saf ; 20(3): 321-334, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33338383

RESUMO

Introduction: Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of neoplasms, whose management requires complex and individualized clinical decisions. Over the last decades the advent of novel medications and advanced diagnostic and therapeutic modalities, alongside our deeper understanding of the disease, revolutionized the landscape of their management, significantly improving both prognosis and quality of life of patients.Area covered: Treatment-related adverse events and safety concerns as demonstrated in clinical trials, as well as in real-world clinical practice.Expert opinion: The only true curative option for NENs remains surgery, whereas high-grade advanced neuroendocrine carcinomas should be primarily managed with platinum-based chemotherapy. For the remaining cases, that comprise the vast majority, the current armamentarium includes somatostatin analogs, interferon, telotristat ethyl, molecular targeted therapies, chemotherapy, peptide receptor radionuclide therapy, and locoregional treatment. The use of the aforementioned therapeutic options is associated with several and not uncommonly severe treatment-related adverse events. However, the benefits offered inclusive of improved prognosis, amelioration of symptoms, and better quality of life amidst others, by far outweighs any adverse event.


Assuntos
Antineoplásicos , Neoplasias Intestinais/terapia , Terapia de Alvo Molecular , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/terapia , Neoplasias Gástricas/terapia , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Humanos , Neoplasias Intestinais/patologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Prognóstico , Qualidade de Vida , Neoplasias Gástricas/patologia
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