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1.
Ann Surg Oncol ; 31(2): 783-791, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37991582

RESUMEN

BACKGROUND: There is an ongoing debate over the prognostic value of the number of examined lymph nodes (ELNs) in cases of gastric signet-ring cell cancer (GSRCC). In this study, we sought to evaluate the correlation between the number of ELNs and the prognosis of GSRCC and identify the optimal number of ELNs. METHODS: A total of 1020 patients diagnosed with GSRCC between 2011 and 2018 in the National Cancer Center database were identified. Clinicopathological characteristics were retrospectively collected, and optimal cutoff values of ELNs were calculated by using X-tile. The impact of different ELNs on overall survival (OS) was compared by using Kaplan-Meier curves. We used univariate and multivariate Cox and subgroup analyses to explore the relationship between ELNs and OS. Furthermore, nonlinear correlations were investigated by using restricted cubic splines (RCSs). RESULTS: X-tile showed that the optimal cutoff value of ELNs was 22. The 5-year OS was higher for patients with ELNs > 22 (vs. ELNs ≤ 22, 66.9% vs. 74.9%, P = 0.026). Multivariate Cox analyses showed that high ELNs were associated with superior OS (hazard ratio = 0.56, 95% confidence interval 0.43-0.74, P < 0.001). In subgroup analyses, the significant association between tumor size > 4 cm, and TNM III stage was still observed. The RCS regression model showed a U-shaped dose-response nonlinear relationship between ELNs and OS; the inflection point, as well as the lowest risk points, corresponded to 44-52 ELNs. CONCLUSIONS: A U-shaped, nonlinear correlation with inflection points of 44-52 ELNs between ELNs and prognosis in GSRCC was identified.


Asunto(s)
Carcinoma de Células en Anillo de Sello , Neoplasias Gástricas , Humanos , Estadificación de Neoplasias , Estudios Retrospectivos , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Pronóstico , Neoplasias Gástricas/patología , Carcinoma de Células en Anillo de Sello/cirugía , Carcinoma de Células en Anillo de Sello/patología
2.
Gastric Cancer ; 27(3): 571-579, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38457083

RESUMEN

BACKGROUND: It remains unclear whether addition of docetaxel to the combination of a platinum and fluoropyrimidine could provide more clinical benefits than doublet chemotherapies in the perioperative treatment for locally advanced gastric/gastro-esophageal junction (LAG/GEJ) cancer in Asia. In this randomized, phase 2 study, we assessed the efficacy and safety of perioperative docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) in LAG/GEJ adenocarcinoma patients. METHODS: Patients with cT3-4 Nany M0 G/GEJ adenocarcinoma were randomized (1:1) to receive 4 cycles of preoperative DOS or SOX followed by D2 gastrectomy and another 4 cycles of postoperative chemotherapy. The primary endpoint was major pathological response (MPR). RESULTS: From Aug, 2015 to Dec, 2019,154 patients were enrolled and 147 patients included in final analysis, with a median age of 60 (26-73) years. DOS resulted in significantly higher MPR (25.4 vs. 11.8%, P = 0.04). R0 resection rate, the 3-year PFS and 3-year OS rates were 78.9 vs. 61.8% (P = 0.02), 52.3 vs. 35% (HR 0.667, 95% CI: 0.432-1.029, Log rank P = 0.07) and 57.5 vs. 49.2% (HR 0.685, 95% CI: 0.429-1.095, Log rank P = 0.11) in the DOS and SOX groups, respectively. Patients who acquired MPR experienced significantly better survival. DOS had similar tolerance to SOX. CONCLUSIONS: Perioperative DOS improved MPR significantly and tended to produce longer PFS compared to SOX in LAG/GEJ cancer in Asia, and might be considered as a preferred option for perioperative chemotherapy and worth further investigation.


Asunto(s)
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Persona de Mediana Edad , Anciano , Docetaxel/uso terapéutico , Oxaliplatino , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Unión Esofagogástrica/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Adenocarcinoma/patología
3.
Dig Dis Sci ; 69(4): 1263-1273, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38451429

RESUMEN

BACKGROUND: A grim prognosis of pancreatic cancer (PCa) was attributed to the difficulty in early diagnosis of the disease. AIMS: Identifying novel biomarkers for early detection of PCa is thus urgent to improve the overall survival rates of patients. METHODS: The study was performed firstly by identification of candidate microRNAs (miRNAs) in formalin-fixed, paraffin-embedded tissues using microarray profiles, and followed by validation in a serum-based cohort study to assess clinical utility of the candidates. In the cohorts, a total of 1273 participants from four centers were retrospectively recruited as two cohorts including training and validation cohort. The collected serum specimens were analyzed by real-time polymerase chain reaction. RESULTS: We identified 27 miRNAs expressed differentially in PCa tissues as compared to the benign. Of which, the top-four was selected as a panel whose diagnostic efficacy was fully assessed in the serum specimens. The panel exhibited superior to CA19-9, CA125, CEA and CA242 in discriminating patients with early stage PCa from healthy controls or non-PCa including chronic pancreatitis as well as pancreatic cystic neoplasms, with the area under the curves (AUC) of 0.971 (95% CI 0.956-0.987) and 0.924 (95% CI 0.899-0.949), respectively. Moreover, the panel eliminated interference from other digestive tumors with a specificity of 90.2%. CONCLUSIONS: A panel of four serum miRNAs was developed showing remarkably discriminative ability of early stage PCa from either healthy controls or other pancreatic diseases, suggesting it may be developed as a novel, noninvasive approach for early screening of PCa in clinic.


Asunto(s)
MicroARNs , Neoplasias Pancreáticas , Humanos , MicroARNs/genética , Estudios Retrospectivos , Estudios de Cohortes , Biomarcadores de Tumor , Detección Precoz del Cáncer , Neoplasias Pancreáticas/patología
4.
BMC Surg ; 22(1): 342, 2022 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-36115993

RESUMEN

PURPOSE: About 15%-40% of gastric cancer patients have peritoneal metastasis, which leads to poor prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) is considered to be an effective treatment for these patients. This study evaluated the efficacy and safety of HIPEC in patients with gastric cancer diagnosed from laboratory tests. METHODS: The clinical and pathological data of 63 patients with gastric cancer who underwent HIPEC in 2017-2021 were prospectively recorded. Fifty-five patients underwent cytoreductive surgery + HIPEC, and eight patients received HIPEC alone. The factors associated with HIPEC safety and efficacy were analyzed. The primary endpoint was overall survival. RESULTS: The average patient age was 54.84 years and 68.3% of patients were male. Moreover, 79.4% of patients had a peritoneal carcinoma index (PCI) score of ≤ 7 and 61.9% had a completeness of cytoreduction score of 0. Because of peritoneal metastasis, 29 patients (46.03%) were classified as stage IV. Laboratory tests showed no differences in pre-HIPEC blood test results compared to post-HIPEC results after removing the effects of surgery. HIPEC treatment did not cause obvious liver or kidney damage. Serum calcium levels decreased significantly after HIPEC (P = 0.0018). The Karnofsky performance status (KPS) score correlated with the patient's physical function and improved after HIPEC (P = 0.0045). In coagulation tests, FDP (P < 0.0001) and D-dimer (P < 0.0001) levels increased significantly and CA242 (P = 0.0159), CA724 (P < 0.0001), and CEA (P < 0.0014) levels decreased significantly after HIPEC. Completeness of cytoreduction score was an independent prognostic factor. HIPEC did not show a survival benefit in patients with gastric cancer (P = 0.5505). CONCLUSION: HIPEC is a safe treatment for patients with gastric cancer with peritoneal metastasis based on the laboratory tests. However, the efficacy of this treatment on gastric-derived peritoneal metastases requires further confirmation.


Asunto(s)
Hipertermia Inducida , Neoplasias Peritoneales , Neoplasias Gástricas , Calcio , Antígeno Carcinoembrionario , China/epidemiología , Terapia Combinada , Femenino , Humanos , Hipertermia Inducida/métodos , Quimioterapia Intraperitoneal Hipertérmica , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Gástricas/patología , Tasa de Supervivencia
5.
BMC Cancer ; 21(1): 20, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-33402102

RESUMEN

BACKGROUND: Curing locally advanced gastric cancer through surgery alone is difficult. Adjuvant and neoadjuvant chemotherapy bring potential benefits to more patients with gastric cancer based on several clinical trials. According to phase II studies and guidelines, SOX regimen as neoadjuvant chemotherapy is efficient. However, the optimal duration of neoadjuvant chemotherapy has not been established. In this study, we will evaluate the efficacy and safety of different cycles of SOX as neoadjuvant chemotherapy for patients with locally advanced gastric cancer. METHODS: RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study which will enroll 524 patients in total. Eligible patients will be registered, pre-enrolled and receive three cycles of SOX, after which tumor response evaluations will be carried out. Those who show stable disease or progressive disease will be excluded. Patients showing complete response or partial response will be enrolled and assigned into either group A for another three cycles of SOX (six cycles in total) followed by D2 surgery; or group B for D2 surgery (three cycles in total). The primary endpoint is the rate of pathological complete response and the secondary endpoints are R0 resection rate, three-year disease-free survival, five-year overall survival, and safety. DISCUSSION: This study is the first phase III randomized trial to compare the cycles of neoadjuvant chemotherapy using SOX for resectable locally advanced cancer. Based on a total of six to eight cycles of perioperative chemotherapy usually applied in locally advanced gastric cancer, patients in group A can be considered to have completed all perioperative chemotherapy, the results of which may suggest the feasibility of using chemotherapy only before surgery in gastric cancer. TRIAL REGISTRATION: Registered prospectively in the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) with registration number ChiCTR1900023293 on May 21st, 2019.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Neoadyuvante , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/patología , Adolescente , Adulto , Anciano , Quimioterapia Adyuvante , Ensayos Clínicos Fase III como Asunto , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Oxaliplatino/administración & dosificación , Ácido Oxónico/administración & dosificación , Pronóstico , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Neoplasias Gástricas/patología , Tegafur/administración & dosificación , Adulto Joven
6.
Neuroendocrinology ; 111(11): 1130-1140, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-31940636

RESUMEN

PURPOSE: To evaluate whether the European Neuroendocrine Tumor Society (ENETS) system or the 8th American Joint Committee on Cancer (AJCC) staging manual are suitable for gastric neuroendocrine carcinomas and/or mixed adenoneuroendocrine carcinomas (G-NECs/MANECs). METHODS: Patients in a multicentric series with G-NEC/MANEC who underwent curative-intent surgical resection for a primary tumor were included. An optimal staging system was proposed base on analysis of the T and N status and validated by the SEER database. RESULTS: Compared with the ENETS system, the survival curves of the T category and N category in the 8th AJCC system were better separated and distributed in a more balanced way, but the survival curves of T2 vs. T3, N0 vs. N1, and N3a vs. N3b overlapped. For the T category, the 8th AJCC T category was modified by combining T2 and T3, which was consistent with the T category in the 6th AJCC manual for GC. For the N category, the optimal cut-off values of metastatic lymph nodes using X-tile were also similar to those of the N category in the 6th AJCC system. The Kaplan-Meier plots of the 6th AJCC system showed statistically significant differences between individual substages. Compared with the other 2 classifications, the 6th AJCC system also showed superior prognostic stratification. Similar results were obtained in both multicentric and SEER validation sets. CONCLUSIONS: Compared to the 8th AJCC and ENETS systems, the 6th AJCC staging system for GC is more suitable for G-NEC/MANEC and can be adopted in clinical practice.


Asunto(s)
Adenocarcinoma/diagnóstico , Carcinoma Neuroendocrino/diagnóstico , Neoplasias Gastrointestinales/diagnóstico , Estadificación de Neoplasias/normas , Tumores Neuroendocrinos/diagnóstico , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Programa de VERF
7.
Gastric Cancer ; 24(2): 503-514, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32915373

RESUMEN

OBJECTIVE: To establish a novel nomogram to predict individual 1, 3, and 5 years disease-free survival (DFS) of patients with gastric neuroendocrine carcinoma/mixed adenoneuroendocrine carcinoma [(MA)NEC]. BACKGROUND: Among patients undergoing radical resection of gastric (MA)NEC, there is still a high tendency for relapse. METHODS: A retrospective analysis of 777 patients with gastric (MA)NEC at 23 centers in China from 2004 to 2015 was performed. Based on the established nomogram, which included age, ASA, pT, pN and Ki67, the overall patients were divided into low-risk group (LRG) and high-risk group (HRG). RESULTS: The median follow-up time was 40 months (1-169 months). The C-index, AUC and time-ROC of the nomogram were significantly higher than that of the 8th edition AJCC and ENETS TNM staging systems. The 3-year DFS of patients in HRG generated by the nomogram was significantly lower than that in LRG (all patients: 35% vs 66.9%, p < 0.001), and there were still significant differences in stratified analysis of the TNM staging systems. The local recurrence rate (10.5% vs 2.6%) and distant recurrence rate (45.1% vs 22.6%) in HRG were significantly higher than those in LRG, especially in anastomotic recurrence (6.3% vs 2%), liver recurrence (20.7% vs 13.4%) and peritoneal metastasis (12.7% vs 2.6%). CONCLUSIONS: Compared with AJCC and ENETS TNM staging systems, the established novel validated nomogram had a significantly better prediction ability for DFS and recurrence patterns in patients with gastric (MA)NEC. It can also compensate for the shortcomings of existing AJCC and ENETS TNM staging in predicting individual recurrence risk.


Asunto(s)
Adenocarcinoma/patología , Carcinoma Neuroendocrino/patología , Recurrencia Local de Neoplasia/etiología , Nomogramas , Neoplasias Gástricas/patología , Adenocarcinoma/cirugía , Anciano , Carcinoma Neuroendocrino/cirugía , Supervivencia sin Enfermedad , Femenino , Gastrectomía , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Medición de Riesgo , Neoplasias Gástricas/cirugía
8.
Chin J Cancer Res ; 33(4): 433-446, 2021 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-34584369

RESUMEN

OBJECTIVE: Quality assurance is crucial for oncological surgical treatment assessment. For rare diseases, single-quality indicators are not enough. We aim to develop a comprehensive and reproducible measurement, called the "Textbook Outcome" (TO), to assess the quality of surgical treatment and prognosis of gastric neuroendocrine carcinoma (G-NEC) patients. METHODS: Data from patients with primary diagnosed G-NEC included in 24 high-volume Chinese hospitals from October 2005 to September 2018 were analyzed. TO included receiving a curative resection, ≥15 lymph nodes examined, no severe postoperative complications, hospital stay ≤21 d, and no hospital readmission ≤30 d after discharge. Hospital variation in TO was analyzed using a case mix-adjusted funnel plot. Prognostic factors of survival and risk factors for non-Textbook Outcome (non-TO) were analyzed using Cox and logistic models, respectively. RESULTS: TO was achieved in 56.6% of 860 G-NEC patients. TO patients had better overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) than non-TO patients (P<0.05). Moreover, TO patients accounted for 60.3% of patients without recurrence. Multivariate Cox analysis revealed non-TO as an independent risk factor for OS, DFS, and RFS of G-NEC patients (P<0.05). Increasing TO rates were associated with improved OS for G-NEC patients, but not hospital volume. Multivariate logistic regression revealed that non-lower tumors, open surgery, and >200 mL blood loss were independent risk factors for non-TO patients (P<0.05). CONCLUSIONS: TO is strongly associated with multicenter surgical quality and prognosis for G-NEC patients. Factors predicting non-TO are identified, which may help guide strategies to optimize G-NEC outcomes.

9.
BMC Cancer ; 20(1): 801, 2020 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-32831061

RESUMEN

BACKGROUND: The main treatment methods for early gastric cancer (EGC) include endoscopic submucosal dissection (ESD) and radical gastrectomy. However, appropriate treatment for patients who exceed the absolute indications for ESD remains unestablished. In China, evidence-based medicine for the expanding indications of ESD and accurate diagnostic staging for EGC patients are lacking. Thus, clinical studies involving Chinese patients with EGC are necessary to select appropriate treatment options and promote China's expanded indications for ESD and diagnostic staging scheme. METHODS: This is a multicenter, ambispective, observational, open-cohort study that is expected to enroll 554 patients with EGC. The study was launched in May 2018 and is scheduled to end in March 2022. All enrolled patients should meet the inclusion criteria. Case report forms and electronic data capture systems are used to obtain clinical data, which includes demographic information, results of perioperative blood- and auxiliary examinations, surgical information, results of postoperative pathology, and the outcomes of postoperative recovery and follow-up. Patients are followed up every 6 months after surgery for a minimum of 5 years. The primary endpoint is the rate of lymph node metastasis (LNM), whereas the secondary endpoints include the following: consistency, sensitivity, and specificity of the results of preoperative examinations and postoperative pathology; cut-off values for LNM; logistic regression model of expanded indications for ESD; and incidence of postoperative complications within the 30-day and 5-year relapse-free survival rates. DISCUSSION: This study will explore and evaluate expanded indications for ESD that match the characteristics of the Chinese population in patients with EGC and will introduce a related staging procedure and examination scheme that is appropriate for China. Ethical approval was obtained from all participating centers. The findings are expected to be disseminated through publications or presentations and will facilitate clinical decision-making in EGC. TRIAL REGISTRATION: The name of the registry is ChiCTR. It was registered on May 9, 2018, with the registration number ( ChiCTR1800016084 ). The clinical trial was launched in May 2018 and will end in March 2022, with enrollment to be completed by December 2021. Trial status: Ongoing.


Asunto(s)
Resección Endoscópica de la Mucosa/normas , Gastroscopía/normas , Recurrencia Local de Neoplasia/epidemiología , Complicaciones Posoperatorias/epidemiología , Neoplasias Gástricas/cirugía , Adolescente , Adulto , Anciano , China/epidemiología , Toma de Decisiones Clínicas/métodos , Supervivencia sin Enfermedad , Resección Endoscópica de la Mucosa/efectos adversos , Medicina Basada en la Evidencia/métodos , Medicina Basada en la Evidencia/normas , Femenino , Estudios de Seguimiento , Mucosa Gástrica/patología , Mucosa Gástrica/cirugía , Gastroscopía/efectos adversos , Humanos , Incidencia , Metástasis Linfática/prevención & control , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Recurrencia Local de Neoplasia/prevención & control , Estudios Observacionales como Asunto , Selección de Paciente , Complicaciones Posoperatorias/etiología , Guías de Práctica Clínica como Asunto , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Adulto Joven
10.
World J Surg Oncol ; 18(1): 43, 2020 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-32106866

RESUMEN

BACKGROUND: Total gastrectomy (TG) is a widely accepted procedure for treating gastric stump cancer (GSC). However, subtotal gastrectomy (SG) would benefit elective patients with GSC. The aim of this study was to clarify the safety and long-term prognosis of SG in treating GSC after distal gastrectomy for benign lesions. METHODS: A total of 53 patients with GSC located at the anastomotic site or gastric body between May 1999 and December 2018 at our hospital were included. In total, 21 patients underwent SG, and the remaining 24 patients underwent TG. Clinicopathological data, operative data, and overall survival (OS) were compared. RESULTS: The operative duration, estimated blood loss volume, and length of hospital stay were similar between the SG and TG groups. The postoperative complications were similar between the two groups, but no cases of anastomotic leakage were noted in the SG group. TG was associated with significantly more retrieved lymph nodes than SG (18.5 ± 11.5 vs. 10.7 ± 9.2; p = 0.017), while the number of metastatic lymph nodes did not differ between the groups (2.9 ± 3.5 vs. 1.9 ± 3.6; p = 0.329). The median survival time in the SG group was 81.0 months (95% confidence interval (CI), 68.906 to 93.094 months), which was similar to the 45.0 months (95% CI, 15.920 to 74.080 months) observed in the TG group (p = 0.236). Both univariate and multivariate analyses showed that tumor location and histological type were prognostic factors, while surgery type was not a prognostic factor. Further stratified analyses according to tumor location revealed that OS was not significantly different between the two groups among patients with tumors located at the anastomotic site, while OS in the TG group was significantly better than that in the SG group among patients with tumors located in the gastric body (p = 0.046). CONCLUSIONS: The results of the current study indicate that SG is a suitable alternative surgical procedure for GSC located at the anastomotic site after distal gastrectomy for benign lesions. The short-term outcomes and long-term prognoses of SG are comparable with those of TG.


Asunto(s)
Adenocarcinoma/cirugía , Gastrectomía/métodos , Muñón Gástrico/patología , Complicaciones Posoperatorias/cirugía , Reoperación/métodos , Neoplasias Gástricas/cirugía , Adenocarcinoma/etiología , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Anastomosis Quirúrgica/efectos adversos , Femenino , Gastrectomía/efectos adversos , Muñón Gástrico/cirugía , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/patología , Pronóstico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Resultado del Tratamiento
13.
Mol Carcinog ; 56(11): 2372-2381, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27433921

RESUMEN

Lef1/Tcfs family, which includes Lef1, Tcf1, Tcf3, and Tcf4, is required for the transcriptional activation induced by ß-catenin. However, whether all the members play the same role in colon carcinogenesis is not clear. We found that Lef1 and Tcf1, but not Tcf3 and Tcf4, were upregulated at both mRNA and protein level with the formation of colon tumor in AOM-DSS mouse model. The same profiles were seen in human specimens with the evolvement from adenoma to adenocarcinoma. Additionally, Lef1 and Tcf1 were correlated with a subgroup of Wnt target genes, including Lgr5, a key gene of intestinal stem cell. Further studies supported the role of Tcf1 on sphere formation and transcriptional regulation of Lgr5 in vitro. Interestingly, 3' UTR of each Lef1/Tcfs member were targeted by diverse miRNAs, which were negatively correlated with respective member in human colon cancer specimens. Furthermore, these miRNAs were verified to repress Tcf1 and Lef1 in vitro. Taken together, Lef1 and Tcf1 showed oncogenic effect in colonic carcinogenesis. Cellular context of miRNAs might play important roles in carcinogenesis by altering the expression pattern of Lef/Tcfs members. © 2017 Wiley Periodicals, Inc.


Asunto(s)
Carcinogénesis/genética , Neoplasias del Colon/genética , Regulación Neoplásica de la Expresión Génica , Factor Nuclear 1-alfa del Hepatocito/genética , Factor de Unión 1 al Potenciador Linfoide/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenoma/genética , Adenoma/patología , Animales , Carcinogénesis/patología , Línea Celular Tumoral , Colon/metabolismo , Colon/patología , Neoplasias del Colon/patología , Humanos , Masculino , Ratones Endogámicos C57BL , MicroARNs/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología
15.
J Biol Chem ; 290(44): 26627-37, 2015 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-26354435

RESUMEN

Proteinase activated-receptor 2 (PAR2) participates in cancer metastasis promoted by serine proteinases. The current study aimed to test the molecular mechanism by which PAR2 promotes cancer cell migration. In different cancer cells, activation of PAR2 by activating peptide (PAR2-AP) dramatically increased cell migration, whereas knock down of PAR2 inhibited cellular motility. The PAR2 activation also repressed miR-125b expression while miR-125b mimic successfully blocked PAR2-induced cell migration. Moreover, Grb associated-binding protein 2 (Gab2) was identified as a novel target gene of miR-125b and it mediated PAR2-induced cell migration. The correlation of PAR2 with miR-125b and Gab2 was further supported by the findings obtained from human colorectal carcinoma specimens. Remarkably, knock down of NOP2/Sun domain family, member 2 (NSun2), a RNA methyltransferase, blocked the reduction in miR-125b induced by PAR2. Furthermore, PAR2 activation increased the level of N(6)-methyladenosine (m(6)A)-containing pre-miR-125b in NSun2-dependent manner. Taken together, our results demonstrated that miR-125b mediates PAR2-induced cancer cell migration by targeting Gab2 and that NSun2-dependent RNA methylation contributes to the down-regulation of miR-125b by PAR2 signaling. These findings suggest a novel epigenetic mechanism by which microenvironment regulates cancer cell migration by altering miRNA expression.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , ARN Neoplásico/metabolismo , Receptor PAR-2/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Sitios de Unión , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Epigénesis Genética , Células HCT116 , Células HT29 , Humanos , Metilación/efectos de los fármacos , Metiltransferasas/antagonistas & inhibidores , Metiltransferasas/genética , Metiltransferasas/metabolismo , MicroARNs/antagonistas & inhibidores , MicroARNs/metabolismo , Oligopéptidos/farmacología , Oligorribonucleótidos/genética , Oligorribonucleótidos/metabolismo , Unión Proteica , ARN Neoplásico/genética , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Receptor PAR-2/metabolismo , Transducción de Señal , Microambiente Tumoral/genética
16.
Chemotherapy ; 61(4): 197-203, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26872008

RESUMEN

BACKGROUND: We investigated the efficacy and safety of biweekly irinotecan and cisplatin (IP) as first-line treatment in advanced gastric cancer patients. METHODS: Irinotecan 125 mg/m2 on day 1 and cisplatin 60 mg/m2 on day 2 were administrated every 14 days. UGT1A1*28/*6 and toxicities were analyzed. RESULTS: Forty-one eligible patients were enrolled. Fifteen patients, who were defined as the high-dose group, received starting doses of irinotecan 125 mg/m2. Twenty-six patients, who were defined as the low-dose group, received starting doses of irinotecan 80 mg/m2 and cisplatin 50 mg/m2. The response rate was 53.3% in the irinotecan high-dose group and 53.8% in the irinotecan low-dose group. The most common grade 3/4 toxicity was neutropenia (68.3%). No significant difference in grade 3/4 neutropenia was found between patients with the wild-type genotype and those with variant genotypes for UGT1A1*28 or UGT1A1*6. CONCLUSIONS: The combination of biweekly irinotecan 80 mg/m2 and cisplatin 50 mg/m2 was active and tolerable. The role of the UGT1A1 genotype in clinical toxicity of an IP regimen requires further investigation.


Asunto(s)
Antineoplásicos/uso terapéutico , Camptotecina/análogos & derivados , Cisplatino/uso terapéutico , Glucuronosiltransferasa/genética , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos/efectos adversos , Camptotecina/efectos adversos , Camptotecina/uso terapéutico , Cisplatino/efectos adversos , Cálculo de Dosificación de Drogas , Quimioterapia Combinada , Femenino , Frecuencia de los Genes , Genotipo , Enfermedades Hematológicas/etiología , Humanos , Irinotecán , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidad , Tomografía Computarizada por Rayos X
17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(6): 1831-6, 2016 Jun.
Artículo en Zh | MEDLINE | ID: mdl-30052401

RESUMEN

The paper uses MSR-16 portable multispectral radiometer made in the USA and computes the numbers of the test units by pulling the formula on the radiometer effective observation area, which solves the problem on the uncertain numbers of computing the times on region visible light band spectral radiation ratio M_D. The paper uses CI-310 portable photosynthesis measurement system made by American CID Company and measures the net photosynthetic rate of a group of soybean plant. M_D and C_D are normalized by the normalization method [0,1]. Then, the normalization data M_D1 and C_D1 are gained . Based on the different test time, M_D1 is divided of M_D11 and M_D12. C_D1 is divided of C_D11 and C_D12. The paper uses polynomial kernel function, gauss kernel function, sigmoid kernel function and bio-selfadaption kernel function constructed by us with Support Vector Machine. Penalty parameter c and parameter g separately are optimized with optimization algorithms such as grid-search,genetic algorithm and particle swarm optimization. Based on the formula epsilon-SVR and the formula nu-SVR with Support Vector Machine, the paper constructs the prediction model on the net photosynthetic rate of a group of soybean plant by using of the cross combination with four kernel functions, three optimization methods and two formulas. The test results are as follows: in the condition of S=17 m2 which is the test plan area of soybean plant and the H=2 m which is the high on MSR-16 portable multispectral radiometer above the canopy of soybean plant, the prediction accuracy is up to 85% on the No.1 prediction set C_D12 and the prediction accuracy is up to 82% on the No.2 prediction set C_D12 based on the model epsilon-SVR-bio-selfadaption-grid-search. In the condition of other combinations with S and H, the prediction accuracy is up to 81% on the No.2 prediction set C_D12 based on the model epsilon-SVR-bio-selfadaption-grid-search. The model epsilon-SVR-bio-selfadaption-grid-search indicates the validity of bio-selfadaption kernel functions which is constructed by our previous research with support vector machine. The model epsilon-SVR-bio-selfadaption-grid-search indicates the rationality of the measure method on visible spectral data in the test area. The model epsilon-SVR-bio-selfadaption-grid-search indicates the feasibility of the prediction method on net photosynthetic rate of soybean plant groups by using of visible spectrum.

18.
Zhonghua Zhong Liu Za Zhi ; 37(5): 371-4, 2015 May.
Artículo en Zh | MEDLINE | ID: mdl-26463029

RESUMEN

OBJECTIVE: To evaluate the value of intraoperative fine needle aspiration cytology (IFNAC) examination in the diagnosis of pancreatic lesions. METHODS: The clinicopathological data of 491 patients with pancreatic lesions treated in our hospital from May 1998 to June 2013 were retrospectively analyzed. Their clinical features, IFNAC findings, pathological results after IFNAC examination and related complications were summarized. The factors affecting the aspiration biopsy accuracy were analyzed using logistic regression and multi factor analysis. RESULTS: 491 patients with pancreatic lesions were examined by IFNAC. Among them, cancer cells were found in 434 cases (positive), and were not found in 57 cases (negative). Among the 310 cases who underwent surgical operation, postoperative pathology confirmed 209 cases of pancreatic ductal adenocarcinoma, 8 cases of pancreatic cystadenocarcinoma, 23 cases of solid pseudopapillary tumor of the pancreas, 15 cases of pancreatic neuroendocrine tumor, 14 cases of intraductal papillary mucinous tumor, 2 cases of primary pancreatic gastrointestinal stromal tumor, 17 cases of pancreatic serous cystadenoma, and 22 cases of chronic mass-forming type pancreatitis. The IFNAC test showed a sensitivity of 97.9% (425/434), and specificity of 89.5% (51/57). The IFNAC examination-related complications were pancreatic leakage in a total of 12 patients which were cured after treatment. No bleeding complication was observed. Logistic multivariate analysis showed that tumor size, cystic degeneration, lymph node metastasis and associated chronic pancreatitis are independent factors affecting the IFNAC examination of pancreatic carcinoma. CONCLUSIONS: IFNAC examination has a high sensitivity and specificity, and with a good safety in clinical use. IFNAC can be used as a powerful tool for the diagnosis of pancreatic cancer, with a high clinical value in use. In the cytology-negative cases, cytology alone can not rule out the diagnosis of pancreatic cancer. Through repeated sampling and combined with intraoperative frozen section pathology can improve the diagnostic accuracy.


Asunto(s)
Biopsia con Aguja Fina , Neoplasias Pancreáticas/diagnóstico , Biopsia con Aguja , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patología , Cistadenoma Seroso/diagnóstico , Cistadenoma Seroso/patología , Secciones por Congelación , Humanos , Páncreas/patología , Neoplasias Pancreáticas/patología , Estudios Retrospectivos , Sensibilidad y Especificidad , Neoplasias Pancreáticas
19.
Front Oncol ; 14: 1341900, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38304873

RESUMEN

Objective: This retrospective study aimed to evaluate the feasibility and safety of intraoperative assessment of anastomotic blood supply in patients undergoing esophagojejunostomy or esophagogastrostomy for gastric cancer using Indocyanine Green Fluorescence Imaging (IGFI). Materials and methods: From January 2019 to October 2021, we conducted a retrospective analysis of patients who had undergone laparoscopic gastrectomy for the treatment of gastric cancer. The patients were consecutively enrolled and categorized into two study groups: the Indocyanine Green Fluorescence Imaging (IGFI) group consisting of 86 patients, and the control group comprising 92 patients. In the IGFI group, intravenous administration of Indocyanine Green (ICG) was performed, and we utilized a fluorescence camera system to assess anastomotic blood supply both before and after the anastomosis. Results: The demographic characteristics of patients in both groups were found to be comparable. In the IGFI group, the mean time to observe perfusion fluorescence was 26.3 ± 12.0 seconds post-ICG injection, and six patients needed to select a more proximal resection point due to insufficient fluorescence at their initial site of choice. Notably, the IGFI group exhibited a lower incidence of postoperative anastomotic leakage, with no significant disparities observed in terms of pathological outcomes, postoperative recovery, or other postoperative complication rates when compared to the control group (p > 0.05). Conclusion: This study underscores the potential of IGFI as a dependable and pragmatic tool for the assessment of anastomotic blood supply following esophagojejunostomy or esophagogastrostomy for gastric cancer. The use of IGFI may potentially reduce the occurrence of postoperative anastomotic leakage.

20.
Front Immunol ; 15: 1365834, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38660300

RESUMEN

Background: Gastric signet ring cell carcinoma (GSRCC) is a rare and highly malignant disease with a poor prognosis. To assess the overall survival (OS) and cancer-specific survival (CSS) of patients with GSRCC, prognostic nomograms were developed and validated using common clinical factors. Methods: This retrospective cohort study included patients diagnosed with GSRCC between 2011 and 2018 from the National Cancer Center (n = 1453) and SEER databases (n = 2745). Prognostic nomograms were established by identifying independent prognostic factors using univariate and multivariate Cox regression analyses. The calibration curve and C-index were used to assess the predictions. The clinical usefulness of the survival prediction model was further evaluated using the DCA and ROC curves. The models were internally validated in the training cohort and externally validated in the validation cohort. Two web servers were created to make the nomogram easier to use. Results: Patients with GSRCC were divided into training (n = 2938) and validation (n = 1260) cohorts. The nomograms incorporated six predictors: age, race, tumor site, tumor size, N stage, T stage, and AJCC stage. Excellent agreement was observed between the internal and exterior calibration plots for the GSRCC survival estimates. The C-index and area under the ROC curve were roughly greater than 0.7. Both nomograms had adequate clinical efficacy, as demonstrated by the DCA plots. Furthermore, we developed a dynamic web application utilizing the constructed nomograms available at https://jiangyujuan.shinyapps.io/OS-nomogram/ and https://jiangyujuan.shinyapps.io/DynNomapp-DFS/. Conclusion: We developed web-based dynamic nomograms utilizing six independent prognostic variables that assist physicians in estimating the OS and CSS of patients with GSRCC.


Asunto(s)
Carcinoma de Células en Anillo de Sello , Nomogramas , Neoplasias Gástricas , Humanos , Carcinoma de Células en Anillo de Sello/mortalidad , Carcinoma de Células en Anillo de Sello/patología , Carcinoma de Células en Anillo de Sello/diagnóstico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Anciano , Internet , Estadificación de Neoplasias , Adulto , Programa de VERF
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