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1.
Ann Surg Oncol ; 31(1): 421-432, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37925653

RESUMO

BACKGROUND: We aimed to construct and validate a deep learning (DL) radiomics nomogram using baseline and restage enhanced computed tomography (CT) images and clinical characteristics to predict the response of metastatic lymph nodes to neoadjuvant chemotherapy (NACT) in locally advanced gastric cancer (LAGC). METHODS: We prospectively enrolled 112 patients with LAGC who received NACT from January 2021 to August 2022. After applying the inclusion and exclusion criteria, 98 patients were randomized 7:3 to the training cohort (n = 68) and validation cohort (n = 30). We established and compared three radiomics signatures based on three phases of CT images before and after NACT, namely radiomics-baseline, radiomics-delta, and radiomics-restage. Then, we developed a clinical model, DL model, and a nomogram to predict the response of LAGC after NACT. We evaluated the predictive accuracy and clinical validity of each model using the receiver operating characteristic curve and decision curve analysis, respectively. RESULTS: The radiomics-delta signature was the best predictor among the three radiomics signatures. So, we developed and validated a DL delta radiomics nomogram (DLDRN). In the validation cohort, the DLDRN produced an area under the receiver operating curve of 0.94 (95% confidence interval, 0.82-0.96) and demonstrated adequate differentiation of good response to NACT. Furthermore, the DLDRN significantly outperformed the clinical model and DL model (p < 0.001). The clinical utility of the DLDRN was confirmed through decision curve analysis. CONCLUSIONS: In patients with LAGC, the DLDRN effectively predicted a therapeutic response in metastatic lymph nodes, which could provide valuable information for individualized treatment.


Assuntos
Aprendizado Profundo , Segunda Neoplasia Primária , Neoplasias Gástricas , Humanos , Linfonodos/diagnóstico por imagem , Terapia Neoadjuvante , Nomogramas , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Tomografia Computadorizada por Raios X
2.
Br J Surg ; 111(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38215239

RESUMO

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.


Assuntos
Laparoscopia , Levamisol/análogos & derivados , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Humanos , Resultado do Tratamento , Estudos de Coortes , Neoplasias Gástricas/cirurgia , Gastrectomia , Pontuação de Propensão , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
3.
World J Surg ; 48(1): 86-96, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38686746

RESUMO

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMN) are very rare, accounting for approximately 0.2%-0.5% of gastrointestinal tumors. We conducted a multicenter retrospective study to explore the impact of different surgical procedures combined with HIPEC on the short-term outcomes and long-term survival of patients. METHODS: We retrospectively analyzed the clinicopathological data of 91 LAMN perforation patients from 9 teaching hospitals over a 10-year period, and divided them into HIPEC group and non-HIPEC group based on whether or not underwent HIPEC. RESULTS: Of the 91 patients with LAMN, 52 were in the HIPEC group and 39 in the non-HIPEC group. The Kaplan-Meier method predicted that 52 patients in the HIPEC group had 5- and 10-year overall survival rates of 82.7% and 76.9%, respectively, compared with predicted survival rates of 51.3% and 46.2% for the 39 patients in the non-HIPEC group, with a statistically significant difference between the two groups (χ2 = 10.622, p = 0.001; χ2 = 10.995, p = 0.001). Compared to the 5-year and 10-year relapse-free survival rates of 75.0% and 65.4% in the HIPEC group, respectively, the 5-year and 10-year relapse-free survival rates of 48.7% and 46.2% in the non-HIPEC group were significant different between the two outcomes (χ2 = 8.063, p = 0.005; χ2 = 6.775, p = 0.009). The incidence of postoperative electrolyte disturbances and hypoalbuminemia was significantly higher in the HIPEC group than in the non-HIPEC group (p = 0.023; p = 0.044). CONCLUSIONS: This study shows that surgery combined with HIPEC can significantly improve 5-year and 10-year overall survival rates and relapse-free survival rates of LAMN perforation patients, without affecting their short-term clinical outcomes.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias do Apêndice , Quimioterapia Intraperitoneal Hipertérmica , Humanos , Estudos Retrospectivos , Masculino , Feminino , Neoplasias do Apêndice/terapia , Neoplasias do Apêndice/mortalidade , Neoplasias do Apêndice/patologia , Pessoa de Meia-Idade , Adulto , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Idoso , Terapia Combinada , Resultado do Tratamento , Taxa de Sobrevida , Gradação de Tumores , Perfuração Intestinal/etiologia , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/mortalidade
4.
Molecules ; 29(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38792058

RESUMO

The 1092 bp F3H gene from Trapa bispinosa Roxb., which was named TbF3H, was cloned and it encodes 363 amino acids. Bioinformatic and phylogenetic tree analyses revealed the high homology of TbF3H with flavanone 3-hydroxylase from other plants. A functional analysis showed that TbF3H of Trapa bispinosa Roxb. encoded a functional flavanone 3-hydroxylase; it catalyzed the formation of dihydrokaempferol (DHK) from naringenin in S. cerevisiae. The promoter strengths were compared by fluorescence microscopy and flow cytometry detection of the fluorescence intensity of the reporter genes initiated by each constitutive promoter (FITC), and DHK production reached 216.7 mg/L by the promoter adjustment strategy and the optimization of fermentation conditions. The results presented in this study will contribute to elucidating DHK biosynthesis in Trapa bispinosa Roxb.


Assuntos
Flavanonas , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Flavanonas/biossíntese , Flavanonas/metabolismo , Filogenia , Regiões Promotoras Genéticas , Clonagem Molecular/métodos , Flavonoides/biossíntese , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fermentação
5.
Ann Surg ; 277(1): e87-e95, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34225299

RESUMO

OBJECTIVE: A large-scale multicenter retrospective cohort study was conducted to compare the short- and long-term outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. SUMMARY OF BACKGROUND DATA: RG is being increasingly used worldwide, but data from large-scale multicenter studies on the short- and long-term oncologic outcomes of RG versus LG are limited. The potential benefits of RG compared with LG for gastric cancer remain controversial. METHODS: Data from eligible patients who underwent RG or LG for gastric cancer of 11 experienced surgeons from 7 centers in China between March 2010 and October 2019 were collected. The RG group was matched 1:1 with the LG group by using propensity score matching. The primary outcome was postoperative complications. RESULTS: After propensity score matching, a well-balanced cohort of 3552 patients was included for further analysis. The occurrence of overall complications (12.6% vs 15.2%, P = 0.023) was lower in the RG group than in the LG group. RG was associated with less blood loss (126.8 vs 142.5 mL, P < 0.001) and more retrieved lymph nodes in total (32.5 vs 30.7, P < 0.001) and in suprapancreatic areas (13.3 vs 11.6, P < 0.001).The long-term oncological outcomes were comparable between the two groups. CONCLUSIONS: The results of this multicenter study demonstrate that RG is a safe and effective treatment for gastric cancer when performed by experienced surgeons, although longer operation time and higher costs are still concerns about RG. This study provides evidence suggesting that RG may represent an alternative surgical treatment to LG.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Resultado do Tratamento , Gastrectomia/métodos , Complicações Pós-Operatórias/cirurgia , China
6.
BMC Gastroenterol ; 23(1): 117, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37041468

RESUMO

OBJECTIVE: To evaluate the multiple factors influencing the survival of elderly patients with locally advanced gastric cancer (LAGC) and develop and validate the novel nomograms for predicting the survival. METHODS: The clinical features of patients treated between 2000 and 2018 were collected and collated from the Surveillance, Epidemiology, and End Results (SEER) database and three medical centres in China, and the patients were randomly divided into a training cohort (3494), internal validation cohort (1497) and external validation cohort (841). Univariate and multivariate analyses of the prognostic values were performed to identify independent prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS), and two nomogram models were developed. Harrell's concordance index (C-index) and calibration curves were employed to assess discrimination and calibration. Decision curve analysis (DCA) and receiver-operating characteristic (ROC) curves were utilized to investigate the clinical usefulness. RESULTS: In the SEER database, the 5-year OS of the patients was 31.08%, while the 5-year CSS of the patients was 44.09%. Furthermore, in the external validation set, the 5-year OS of the patients was 49.58%, and the 5-year CSS of these patients was 53.51%. After statistical analysis, nine independent prognostic factors of OS and CSS were identified, including age, race, tumour size, differentiation, TNM stage, gastrectomy type, lymph node metastasis (LNM), lymph node ratio (LNR) and chemotherapy. The C-index (approximately 0.7) and calibration curve (close to the optimal calibration line) indicated satisfactory discrimination and calibration of the nomogram. DCA and ROC curves showed that the developed nomogram was superior to TNM stage. CONCLUSION: The novel validated nomogram could accurately predict the prognosis of individual elderly patients with LAGC and guide the selection of clinical treatment measures.


Assuntos
Segunda Neoplasia Primária , Neoplasias Gástricas , Idoso , Humanos , Nomogramas , Gastrectomia , Projetos de Pesquisa
7.
Surg Endosc ; 37(9): 6930-6942, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37328591

RESUMO

BACKGROUND: Some studies have demonstrated the short-term recovery course for patients who underwent laparoscopic gastrectomy according to preoperative computed tomography angiography (CTA) assessment. However, reports of the long-term oncological outcomes are still limited. METHODS: The data of 988 consecutive patients who underwent laparoscopic or robotic radical gastrectomy between January 2014 and September 2018 were analyzed retrospectively at our center, and propensity score matching was used to eliminate bias. Study cohorts were divided into the CTA group (n = 498) and the non-CTA group (n = 490) depending on whether preoperative CTA was available. The primary and secondary endpoints were the 3-year overall survival (OS) and disease-free survival (DFS) rates and the intraoperative course and short-term outcomes, respectively. RESULTS: 431 patients were included in each group after PSM. Compared with the non-CTA group, the CTA group had more harvested lymph nodes and less operative time, blood loss, intraoperative vascular injury and total cost, especially in the subgroup analysis with BMI ≥ 25 kg/m2 patients. There was no difference in the 3 year OS and DFS between the CTA group and the non-CTA group. When further stratified by BMI < 25 or ≥ 25 kg/m2, the 3-year OS and DFS were significantly higher in the CTA group than in the non-CTA group in terms of BMI ≥ 25 kg/m2. CONCLUSIONS: Laparoscopic or robotic radical gastrectomy based on preoperative perigastric artery CTA surgical decision-making has the possibility of improving short-term outcomes. However, there is no difference in the long-term prognosis, except for a subgroup of patients with BMI ≥ 25 kg/m2.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Angiografia por Tomografia Computadorizada , Pontuação de Propensão , Neoplasias Gástricas/cirurgia , Gastrectomia/métodos , Laparoscopia/métodos , Artérias/patologia , Resultado do Tratamento
8.
Surg Endosc ; 37(8): 5902-5915, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37072637

RESUMO

BACKGROUND: This study was performed to evaluate the safety and efficacy of laparoscopic gastrectomy (LG) in patients with locally advanced gastric cancer (LAGC) who received neoadjuvant chemotherapy (NACT). METHODS: We retrospectively analyzed patients who underwent gastrectomy for LAGC (cT2-4aN+M0) after NACT from January 2015 to December 2019. The patients were divided into a LG group and an open gastrectomy (OG) group. The short- and long-term outcomes in both groups were examined following propensity score matching. RESULTS: We retrospectively reviewed 288 patients with LAGC who underwent gastrectomy following NACT. Of these 288 patients, 218 were enrolled; after 1:1 propensity score matching, each group comprised 81 patients. The LG group had significantly lower estimated blood loss than the OG group [80 (50-110) vs. 280 (210-320) mL, P < 0.001) but a longer operation time [205 (186.5-222.5) vs. 182 (170-190) min, P < 0.001], a lower postoperative complication rate (24.7% vs. 42.0%, P = 0.002), and a shorter postoperative hospitalization period [8 (7-10) vs. 10 (8-11.5) days, P = 0.001]. Subgroup analysis revealed that patients who underwent laparoscopic distal gastrectomy had a lower rate of postoperative complications than patients in the OG group (18.8% vs. 38.6%, P = 0.034); however, such a pattern was not seen in patients who underwent total gastrectomy (32.3% vs. 45.9%, P = 0.251). The 3-year matched cohort analysis showed no significant difference in overall survival or recurrence-free survival (log-rank P = 0.816 and P = 0.726, respectively) (71.3% and 65.0% in OG vs. 69.1% and 61.7% in LG, respectively). CONCLUSION: In the short term, LG following NACT is safer and more effective than OG. However, the long-term results are comparable.


Assuntos
Laparoscopia , Neoplasias Gástricas , Humanos , Terapia Neoadjuvante , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Estudos Retrospectivos , Pontuação de Propensão , Gastrectomia/métodos , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento
9.
Ann Surg ; 275(1): e15-e21, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33856385

RESUMO

OBJECTIVE: This study aimed to compare the effects of ERAS and conventional programs on short-term outcomes after LDG. SUMMARY OF BACKGROUND DATA: Currently, the ERAS program is broadly applied in surgical areas. Although several benefits of LDG with the ERAS program have been covered, high-level evidence is still limited, specifically in advanced gastric cancer. METHODS: The present study was designed as a randomized, multicenter, unblinded trial. The enrollment criteria included histologically confirmed cT2-4aN0-3M0 gastric adenocarcinoma. Postoperative complications, mortality, readmission, medical costs, recovery, and laboratory outcomes were compared between the ERAS and conventional groups. RESULTS: Between April 2019 and May 2020, 400 consecutive patients who met the enrollment criteria were enrolled. They were randomly allocated to either the ERAS group (n = 200) or the conventional group (n = 200). After excluding patients who did not undergo surgery or gastrectomy, 370 patients were analyzed. The patient demographic characteristics were not different between the 2 groups. The conventional group had a significantly longer allowed day of discharge and postoperative hospital stay (6.96 vs 5.83 days, P < 0.001; 8.85 vs 7.27 days, P < 0.001); a longer time to first flatus, liquid intake and ambulation (3.37 vs 2.52 days, P < 0.001; 3.09 vs 1.13 days, P < 0.001; 2.85 vs 1.38 days, P < 0.001, respectively); and higher medical costs (6826 vs 6328 $, P = 0.027) than the ERAS group. Additionally, patients in the ERAS group were more likely to initiate adjuvant chemotherapy earlier (29 vs 32 days, P = 0.035). There was no significant difference in postoperative complications or in the mortality or readmission rates. Regarding laboratory outcomes, the procalcitonin and C-reactive protein levels on postoperative day 3 were significantly lower and the hemoglobin levels on postoperative day 5 were significantly higher in the ERAS group than in the conventional group. CONCLUSION: The ERAS program provides a faster recovery, a shorter postoperative hospitalization length, and lower medical costs after LDG without increasing complication and readmission rates. Moreover, enhanced recovery in the ERAS group enables early initiation of adjuvant chemotherapy.


Assuntos
Adenocarcinoma/terapia , Recuperação Pós-Cirúrgica Melhorada/normas , Gastrectomia/métodos , Laparoscopia/métodos , Neoplasias Gástricas/terapia , Adenocarcinoma/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Neoplasias Gástricas/diagnóstico , Fatores de Tempo , Adulto Jovem
10.
BMC Cancer ; 22(1): 1091, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36284263

RESUMO

BACKGROUND: Neuro-oncological ventral antigen 1 (NOVA1) is a neuron-specific RNA-binding protein which regulates alternative splicing in the developing nervous system. Recent research has found that NOVA1 plays a significant role in carcinogenesis. In this paper, we examine the role of NOVA1 in non-small cell lung cancer (NSCLC) and its underlying molecular mechanisms. METHODS: The expression of NOVA1 in NSCLC was detected by immunohistochemistry and correlations between NOVA1 expression and clinicopathological factors were analyzed by chi-square tests. Kaplan-Meier survival analysis and the Cox regression model were used to evaluate the predictive effect of prognostic factors. Western blotting, Cell Counting Kit-8, colony formation, apoptosis, migration and invasion assays were used to detect the effects of silencing (si)NOVA1 RNA on Wnt/ß-catenin signaling and biological behavior in NSCLC cell lines. RESULTS: Our study showed that expression of NOVA1 was up-regulated and significantly correlated with poor differentiation (p = 0.020), advanced TNM stage (P = 0.001), T stage (P = 0.001) and lymph node metastasis (P = 0.000) as well as the expression of ß-catenin (P = 0.012) in NSCLC. The down-regulation of NSCLC by siRNA significantly inhibited proliferation, migration and invasion and promoted apoptosis in NSCLC cells. Expression of Wnt signaling molecules, including ß-catenin, activated ß-catenin, cyclin D1, matrix metalloproteinase (MMP)-2 and MMP-7, was also significantly reduced by siNOVA1. The inhibition of Wnt/ß-catenin signaling in A549 and H1299 cells by siNOVA1 was reversed after treatment with a ß-catenin expression plasmid. CONCLUSION: The present study suggests that NOVA1 may serve as a potential prognosis biomarker in NSCLC. High NOVA1 expression was associated with poor survival rate. Finally, in vitro experiments verified that NOVA1 promotes NSCLC cell proliferation and invasion by regulating Wnt/ß-catenin signaling.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Via de Sinalização Wnt , Ciclina D1/genética , Metaloproteinase 7 da Matriz/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Neoplasias Pulmonares/patologia , RNA Interferente Pequeno/farmacologia , Antígeno Neuro-Oncológico Ventral , Proliferação de Células/genética , Prognóstico , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Biomarcadores , Movimento Celular/genética , Linhagem Celular Tumoral
11.
Surg Endosc ; 36(1): 185-195, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33427913

RESUMO

BACKGROUND: Research on short-term outcomes and oncology results after robotic gastrectomy (RG) is still limited, especially from a single surgical team. The purpose of this study was to compare the short-term and long-term outcomes of robotic and laparoscopic gastrectomy (LG). METHODS: Between October 2014 and September 2019, 1686 consecutive patients who underwent MIS gastrectomy were enrolled. The patients were divided into RG and LG groups according to surgical type. Groups were matched at a 1:1 ratio using propensity scores based on the following variables: age, sex, ASA score, primary tumor location, histologic type, pathological stage, and neoadjuvant chemotherapy. The primary outcomes were 3-year overall survival (OS) and relapse-free survival (RFS). The secondary outcomes were postoperative short-term outcomes. RESULTS: Demographic and baseline characteristics were similar between the two groups after matching. Compared to the LG group, the RG group had a significantly higher retrieved lymph node (LN) number (32.15 vs 30.82, P = 0.040), more retrieved supra-pancreatic LNs (12.45 vs 11.61, P = 0.028), lower estimated blood loss (73.67 vs 98.08 ml, P < 0.001), but longer operation time (205.18 vs 185.27 min, P < 0.001) and higher hospitalization costs ($13,607 vs $10,928, P < 0.001) in the matched cohort. In the subgroup analysis, we observed that compared with LG, patients with advanced gastric cancer benefitted more from RG surgery. The matched cohort analysis demonstrated no statistically significant differences for 3-year OS or RFS (log-rank, P = 0.648 and P = 0.951, respectively): 80.3% and 77.0% in LG vs. 81.2% and 76.6% in RG, respectively. CONCLUSION: RG has certain technical advantages over LG, especially in patients with advanced gastric cancer. However, RG does not improve long-term oncology outcomes.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Gastrectomia/métodos , Humanos , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Gástricas/patologia , Resultado do Tratamento
12.
Int J Med Sci ; 19(2): 338-351, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35165519

RESUMO

Mitogen-inducible gene 6 (Mig-6) is a tumor suppressor gene that plays an important role in many types of cancers by interacting with EGFR. However, its molecular mechanism in hepatocellular carcinoma (HCC) and its relationship with miRNAs need to be elucidated. Therefore, this study aimed to explore whether Mig-6 could promote apoptosis and the inhibition of autophagy via its downstream miRNA in HCC cell lines. We used two cell lines, HepG2 and HLE, to establish Mig-6 overexpression and knockdown experiments, as well as miR-193a mimic and inhibitor experiments. The miRNA microarray profiling was also used to verify Mig-6-regulated miRNA. We found that Mig-6 induced apoptosis and reduced autophagy of HCC cell lines. miR-193a-3p is a Mig-6-regulated miRNA in the Mig-6-overexpression model. It affected the apoptosis and autophagy of HCC cells, at least partly by regulating the expression of TGF-ß2. Additionally, the relationship between Mig-6 and transforming growth factor TGF-ß2 was explored in depth for the first time. These findings revealed an important role of Mig-6 in the apoptosis and autophagy of HCC cells by regulating miR-193a-3p, providing a novel insight into the therapeutic target in HCC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Autofagia/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Apoptose/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Fator de Crescimento Transformador beta2/metabolismo
13.
Int J Med Sci ; 18(9): 2051-2062, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33850476

RESUMO

Background: Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2 or TNFAIP8L2) is a newly discovered negative immune regulator. Studies have shown that TIPE2 causes significant malignant biological effects and is differentially expressed in various malignant tumors. However, the expression and roles of TIPE2 in pancreatic ductal adenocarcinoma (PDAC) are largely unknown. Materials and Methods: The expression of TIPE2 in PDAC tissues was assessed by immunohistochemistry, qPCR and western blot analysis and related clinicopathological parameters including survival time were analyzed. After overexpression of TIPE2, cell proliferation and apoptosis analysis were conducted, and the associated underlying molecular mechanism was also explored. Results: In the present study, TIPE2 was upregulated in early PDAC tissues, and TIPE2 expression decreased as the tumor progressed (P<0.001). TIPE2 expression was negatively associated with tumor size, TNM stage and metastasis of lymph nodes. Furthermore, as an independent risk factor, TIPE2 could be used to predict the survival of patients with PDAC (P=0.035). TIPE2 overexpression significantly suppressed the viability, proliferation and induced apoptosis of PDAC cells by inhibiting survivin and increasing the activity of caspase3/7. Conclusions: For the first time, this study demonstrated that TIPE2 is an independent prognostic factor in PDAC. TIPE2 inhibited the proliferation and induced apoptosis via regulating survivin/caspase3/7 signaling pathway. These results indicated that TIPE2 is a potential biomarker for predicting the prognosis of PDAC patients and plays a pivotal role in the progression of PDAC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/mortalidade , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Pancreáticas/mortalidade , Apoptose/genética , Biomarcadores Tumorais/análise , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/análise , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Pâncreas/patologia , Pâncreas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Transdução de Sinais/genética , Survivina/metabolismo , Regulação para Cima
14.
Eur Heart J ; 41(27): 2523-2536, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32588060

RESUMO

AIM: The present study aimed to assess the benefits of two-stent techniques for patients with DEFINITION criteria-defined complex coronary bifurcation lesions. METHODS AND RESULTS: In total, 653 patients with complex bifurcation lesions at 49 international centres were randomly assigned to undergo the systematic two-stent technique (two-stent group) or provisional stenting (provisional group). The primary endpoint was the composite of target lesion failure (TLF) at the 1-year follow-up, including cardiac death, target vessel myocardial infarction (TVMI), and clinically driven target lesion revascularization (TLR). The safety endpoint was definite or probable stent thrombosis. At the 1-year follow-up, TLF occurred in 37 (11.4%) and 20 (6.1%) patients in the provisional and two-stent groups, respectively [77.8%: double-kissing crush; hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.30-0.90; P = 0.019], largely driven by increased TVMI (7.1%, HR 0.43, 95% CI 0.20-0.90; P = 0.025) and clinically driven TLR (5.5%, HR 0.43, 95% CI 0.19-1.00; P = 0.049) in the provisional group. At the 1 year after indexed procedures, the incidence of cardiac death was 2.5% in the provisional group, non-significant to 2.1% in the two-stent group (HR 0.86, 95% CI 0.31-2.37; P = 0.772). CONCLUSION: For DEFINITION criteria-defined complex coronary bifurcation lesions, the systematic two-stent approach was associated with a significant improvement in clinical outcomes compared with the provisional stenting approach. Further study is urgently warranted to identify the mechanisms contributing to the increased rate of TVMI after provisional stenting. STUDY REGISTRATION: http://www.clinicaltrials.com; Identifier: NCT02284750.


Assuntos
Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Angiografia Coronária , Doença da Artéria Coronariana/cirurgia , Humanos , Stents , Fatores de Tempo , Resultado do Tratamento
15.
Molecules ; 26(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34500767

RESUMO

Chitosan (CTS) is a deacetylated derivative of chitin that is involved in adaptive response to abiotic stresses. However, the regulatory role of CTS in heat tolerance is still not fully understood in plants, especially in grass species. The aim of this study was to investigate whether the CTS could reduce heat-induced senescence and damage to creeping bentgrass associated with alterations in antioxidant defense, chlorophyll (Chl) metabolism, and the heat shock pathway. Plants were pretreated exogenously with or without CTS (0.1 g L-1) before being exposed to normal (23/18 °C) or high-temperature (38/33 °C) conditions for 15 days. Heat stress induced detrimental effects, including declines in leaf relative water content and photochemical efficiency, but significantly increased reactive oxygen species (ROS) accumulation, membrane lipid peroxidation, and Chl loss in leaves. The exogenous application of CTS significantly alleviated heat-induced damage in creeping bentgrass leaves by ameliorating water balance, ROS scavenging, the maintenance of Chl metabolism, and photosynthesis. Compared to untreated plants under heat stress, CTS-treated creeping bentgrass exhibited a significantly higher transcription level of genes involved in Chl biosynthesis (AsPBGD and AsCHLH), as well as a lower expression level of Chl degradation-related gene (AsPPH) and senescence-associated genes (AsSAG12, AsSAG39, Asl20, and Ash36), thus reducing leaf senescence and enhancing photosynthetic performance under heat stress. In addition, the foliar application of CTS significantly improved antioxidant enzyme activities (SOD, CAT, POD, and APX), thereby effectively reducing heat-induced oxidative damage. Furthermore, heat tolerance regulated by the CTS in creeping bentgrass was also associated with the heat shock pathway, since AsHSFA-6a and AsHSP82 were significantly up-regulated by the CTS during heat stress. The potential mechanisms of CTS-regulated thermotolerance associated with other metabolic pathways still need to be further studied in grass species.


Assuntos
Agrostis/efeitos dos fármacos , Antioxidantes/farmacologia , Quitosana/farmacologia , Clorofila/metabolismo , Temperatura Alta , Folhas de Planta/efeitos dos fármacos , Agrostis/metabolismo , Resposta ao Choque Térmico/efeitos dos fármacos , Folhas de Planta/metabolismo
16.
Med Sci Monit ; 26: e926347, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038207

RESUMO

BACKGROUND Enhanced Recovery After Surgery (ERAS) programs can optimize clinical outcomes and have been widely used across multiple specialties, but a personalized prediction model involving ERAS for the prognosis of gastric cancer is lacking. MATERIAL AND METHODS We retrospectively collected clinical data on 725 gastric cancer patients within ERAS who underwent curative gastric resection in the Affiliated Hospital of Qingdao University from 2007 to 2014. Kaplan-Meier method, log-rank test, and Cox proportional risk model were used to determine the independent prognostic factors of patients. The accuracy of model was evaluated by C-index, calibration curve, and Decision Curve Analysis (DCA), and the receiver operator characteristic (ROC) curve was used to compare the nomogram model with the predictive value of TNM staging system. RESULTS The 5-year overall survival (OS) of 725 patients within ERAS was 72.5%. Age at diagnosis, T stage, N stage, and postoperative complications were determined to be independent factors affecting the prognosis of patients within ERAS, and nomogram model was constructed. The C-index of the training group was 0.809 and that of the verification group was 0.804; the calibration curves and DCA of the 2 groups showed good accuracy. Through verification, we found that, compared with the TNM staging assessment method, the nomogram model was more accurate in predicting the prognosis of gastric cancer. CONCLUSIONS This study identified factors affecting the prognosis of patients with gastric cancer, and we constructed the first prognostic nomogram model in ERAS mode to facilitate postoperative personalized prognostic evaluation.


Assuntos
Gastrectomia , Nomogramas , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxa de Sobrevida
17.
J Med Internet Res ; 22(2): e14122, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-32130123

RESUMO

BACKGROUND: With the increasing number of cancer treatments, the emergence of multidisciplinary teams (MDTs) provides patients with personalized treatment options. In recent years, artificial intelligence (AI) has developed rapidly in the medical field. There has been a gradual tendency to replace traditional diagnosis and treatment with AI. IBM Watson for Oncology (WFO) has been proven to be useful for decision-making in breast cancer and lung cancer, but to date, research on gastric cancer is limited. OBJECTIVE: This study compared the concordance of WFO with MDT and investigated the impact on patient prognosis. METHODS: This study retrospectively analyzed eligible patients (N=235) with gastric cancer who were evaluated by an MDT, received corresponding recommended treatment, and underwent follow-up. Thereafter, physicians inputted the information of all patients into WFO manually, and the results were compared with the treatment programs recommended by the MDT. If the MDT treatment program was classified as "recommended" or "considered" by WFO, we considered the results concordant. All patients were divided into a concordant group and a nonconcordant group according to whether the WFO and MDT treatment programs were concordant. The prognoses of the two groups were analyzed. RESULTS: The overall concordance of WFO and the MDT was 54.5% (128/235) in this study. The subgroup analysis found that concordance was less likely in patients with human epidermal growth factor receptor 2 (HER2)-positive tumors than in patients with HER2-negative tumors (P=.02). Age, Eastern Cooperative Oncology Group performance status, differentiation type, and clinical stage were not found to affect concordance. Among all patients, the survival time was significantly better in concordant patients than in nonconcordant patients (P<.001). Multivariate analysis revealed that concordance was an independent prognostic factor of overall survival in patients with gastric cancer (hazard ratio 0.312 [95% CI 0.187-0.521]). CONCLUSIONS: The treatment recommendations made by WFO and the MDT were mostly concordant in gastric cancer patients. If the WFO options are updated to include local treatment programs, the concordance will greatly improve. The HER2 status of patients with gastric cancer had a strong effect on the likelihood of concordance. Generally, survival was better in concordant patients than in nonconcordant patients.


Assuntos
Tomada de Decisão Clínica/métodos , Oncologia/métodos , Equipe de Assistência ao Paciente/normas , Neoplasias Gástricas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
20.
J Vasc Surg ; 67(1): 300-308.e2, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28479097

RESUMO

OBJECTIVE: Animal models are required to explore the mechanisms of and therapy for proximal descending thoracic aortic aneurysm (TAA). This study aimed to establish a reproducible swine model of proximal descending TAA that can further explain the occurrence and progression of proximal descending TAA. METHODS: Eighteen Chinese Wuzhishan miniature pigs (30.32 ± 1.34 kg) were randomized into the elastase group (n = 12) and the control group (n = 6). The elastase group received intra-adventitial injections of elastase (5 mL, 20 mg/mL), and the control group received injections of physiologic saline solution. A 4-cm descending thoracic aortic segment proximal to the left subclavian artery was isolated. The distance between the left subclavian artery and the injection starting point of the descending thoracic aorta was 0.5 cm. Elastic protease was circumferentially injected intra-adventitially into the isolated segment of the aortic wall in the elastase group by a handmade bent syringe. The length of the elastic protease injection was 2 cm. An average of 12 injection points were distributed in this 2-cm aortic segment. Each injection point used about 0.4 mL of elastic protease. The distance between two injection points was about 1.5 cm. All animals underwent digital subtraction angiography preoperatively and 3 weeks after operation. Three weeks after TAA induction, aortas were harvested for biochemical and histologic measurements. RESULTS: All animals in the elastase group developed TAAs. No aneurysms were observed in the control group. The distance between the left subclavian artery and the TAA was 8.00 ± 4.19 mm. Preoperative and postoperative aortic diameters of the elastase group were 15.42 ± 0.43 mm and 24.53 ± 1.41 mm, respectively (P < .0001). Preoperative and postoperative aortic diameters of the control group were 15.31 ± 0.33 mm and 15.57 ± 0.40 mm, respectively (P = .5211). The changes of aortic structure and composition included reduction of smooth muscle cells and degradation of elastic fibers. Levels of matrix metalloproteinases 2 and 9 were increased in TAA tissue. CONCLUSIONS: This study established a reproducible large animal model of proximal descending TAA. This model has the same biochemical characteristics as human aneurysms in the aspects of aortic expansion, aortic middle-level degeneration, and changes in the levels of matrix metalloproteinases and provides a platform for further study.


Assuntos
Túnica Adventícia/efeitos dos fármacos , Aorta Torácica/efeitos dos fármacos , Aneurisma da Aorta Torácica/induzido quimicamente , Modelos Animais de Doenças , Elastase Pancreática/farmacologia , Porco Miniatura/fisiologia , Túnica Adventícia/patologia , Angiografia Digital , Animais , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/patologia , Progressão da Doença , Tecido Elástico/efeitos dos fármacos , Tecido Elástico/patologia , Humanos , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Distribuição Aleatória , Suínos/fisiologia , Porco Miniatura/anatomia & histologia
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