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1.
BMC Geriatr ; 23(1): 463, 2023 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-37525094

RESUMO

BACKGROUND: Sarcopenia is highly prevalent in elderly individuals and has a significant adverse effect on their physical health and quality of life, but the mechanisms remain unclear. Studies have indicated that transcription factors (TFs) and the immune microenvironment play a vital role in skeletal muscle atrophy. METHODS: RNA-seq data of 40 muscle samples were downloaded from the GEO database. Then, differentially expressed genes (DEGs), TFs(DETFs), pathways(DEPs), and the expression of immune gene sets were identified with limma, edgeR, GO, KEGG, ORA, GSVA, and ssGSEA. Furthermore, the results above were integrated into coexpression analysis by Pearson correlation analysis (PCA). Significant coexpression patterns were used to construct the immune-related transcriptional regulatory network by Cytoscape and potential medicine targeting the network was screened by Connectivity Map. Finally, the regulatory mechanisms and RNA expression of DEGs and DETFs were identified by multiple online databases and RT‒qPCR. RESULTS: We screened 808 DEGs (log2 fold change (FC) > 1 or < - 1, p < 0.05), 4 DETFs (log2FC > 0.7 or < - 0.7, p < 0.05), 304 DEPs (enrichment scores (ES) > 1 or < - 1, p < 0.05), and 1208 differentially expressed immune genes sets (DEIGSs) (p < 0.01). Based on the results of PCA (correlation coefficient (CC) > 0.4 or < - 0.4, p < 0.01), we then structured an immune-related network with 4 DETFs, 9 final DEGs, 11 final DEPs, and 6 final DEIGSs. Combining the results of online databases and in vitro experiments, we found that PAX5-SERPINA5-PI3K/Akt (CC ≤ 0.444, p ≤ 0.004) was a potential transcriptional regulation axis, and B cells (R = 0.437, p = 0.005) may play a vital role in this signal transduction. Finally, the compound of trichostatin A (enrichment = -0.365, specificity = 0.4257, p < 0.0001) might be a potential medicine for sarcopenia based on the PubChem database and the result of the literature review. CONCLUSIONS: We first identified immune-related transcriptional regulatory network with high-throughput RNA-seq data in sarcopenia. We hypothesized that PAX5-SERPIAN5-PI3K/Akt axis is a potential mechanism in sarcopenia and that B cells may play a vital role in this signal transduction. In addition, trichostatin A might be a potential medicine for sarcopenia.


Assuntos
Perfilação da Expressão Gênica , Sarcopenia , Humanos , Idoso , Perfilação da Expressão Gênica/métodos , Sarcopenia/genética , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Qualidade de Vida
2.
Ann Surg Oncol ; 29(4): 2348-2358, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34797480

RESUMO

BACKGROUND: Sarcopenia and cachexia are two predictors of adverse clinical outcomes, but they are partly overlapping. We aimed to compare the characteristics and prognostic value of cachexia and sarcopenia in patients after gastrectomy. METHODS: From 2014 to 2019, a total of 1215 gastric cancer patients were enrolled. Cachexia and sarcopenia were diagnosed according to the most recent consensus definitions. Baseline characteristics and clinical outcomes were compared between the two groups. Risk factors of survival were evaluated by Cox regression analysis. RESULTS: Of all patients, 26.5% were diagnosed with cachexia and 19.8% were diagnosed with sarcopenia. Sarcopenia was more prevalent in elderly patients, while cachexia was prone to occur in patients with TMN stage III. Survival curves showed that sarcopenia had adverse effects in patients with TMN stage I and II-III, while cachexia was only associated with poor survival at stages II-III. For the entire cohort, both cachexia and sarcopenia were adverse factors for prognosis. However, for stage I patients, sarcopenia was an independent predictor for overall survival (OS) (HR = 4.939, P < 0.001) and disease-free survival (DFS) (HR = 4.256, P < 0.001), but not cachexia; for stage II-III patients, cachexia was an independent predictor for OS (HR = 1.538, P < 0.001) and DFS (HR = 1.473, P = 0.001), but not sarcopenia. CONCLUSIONS: Sarcopenia and cachexia have different clinical characteristics and prognostic values. For patients with early stage gastric cancer, detection for sarcopenia was more meaningful than cachexia. However, the prognostic significance of cachexia exceeded sarcopenia in advanced cancer.


Assuntos
Sarcopenia , Neoplasias Gástricas , Idoso , Caquexia/complicações , Gastrectomia/efeitos adversos , Humanos , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Sarcopenia/complicações , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia
3.
Surg Endosc ; 35(1): 476-485, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32989539

RESUMO

BACKGROUND: In patients with ultralow rectal cancer, surgical resection of the tumor without impairing sphincter function remains a technical challenge. The purpose of this study was to describe a new technique of transanal natural orifice specimen extraction (NOSE) surgery using our independently developed devices, aiming to achieve precise cancer resection and preserve sphincter function in patients with ultralow rectal cancer. METHODS: Precision functional sphincter-preserving surgery (PPS) was performed on nineteen patients with ultralow rectal cancer between June 2019 and April 2020. With the help of our independently developed devices, surgeons directly and accurately removed the lower edge of the tumor and retained healthy rectal tissue on the nontumorous side. Hand-sewn anastomosis with a mattress suture was used to achieve sturdy anastomosis. Preoperative baseline characteristics, operative details, 90-day postoperative complications, costs, and anal function score at 6 months after surgery were documented. RESULTS: Nineteen ultralow rectal cancer patients with a median distance to the dentate line of 2.0 cm successfully underwent PPS without serious postoperative complications. Six out of nineteen patients (31.6%) received a prophylactic stoma. The average cost was 62164.1 yuan. At 6 months after surgery, the average Wexner anal function score and the average Vaizey score were both 3 points. CONCLUSIONS: PPS can be employed to precisely resect rectal tumors and preserve sphincter function in ultralow rectal cancer patients. The use of our devices enhanced surgical efficiency, reduced the need for prophylactic stoma, reduced surgery-related costs, and prevented abdominal surgical incisions.


Assuntos
Cirurgia Endoscópica por Orifício Natural/métodos , Neoplasias Retais/cirurgia , Idoso , Canal Anal/cirurgia , Anastomose Cirúrgica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Cirurgia Endoscópica por Orifício Natural/instrumentação , Tratamentos com Preservação do Órgão , Complicações Pós-Operatórias/etiologia , Reto/cirurgia , Estomas Cirúrgicos
4.
Langenbecks Arch Surg ; 406(2): 449-461, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32880728

RESUMO

PURPOSE: The applicability of laparoscopic-assisted radical gastrectomy for elderly patients with gastric cancer is still not well clarified. The aim of this double-center study was to explore the feasibility and effectiveness of laparoscopic-assisted radical gastrectomy on elderly patients with gastric cancer. METHODS: We prospectively collected data of patients who underwent gastrectomy for cancer in two centers from June 2016 to December 2019. Propensity score matching was performed at a ratio of 1:1 to compare the laparoscopic-assisted radical gastrectomy group and open radical gastrectomy group. Univariate analyses and multivariate logistic regression analyses evaluating the risk factors for total, surgical, and medical complications were performed. RESULTS: A total of 481 patients with gastric cancer met the inclusion criteria and were included in this study. After propensity score analysis, 258 patients were matched each other (laparoscopic-assisted radical gastrectomy (LAG) group, n = 129; open radical gastrectomy (OG) group, n = 129). LAG group had lower rate of surgical complications (P = 0.009), lower rate of severe complications (P = 0.046), shorter postoperative hospital stay (P = 0.001), and lower readmission rate (P = 0.039). Multivariate analyses revealed that anemia, Charlson comorbidity index, and combined resection were independent risk factors in the LAG group, whereas body mass index and American Society of Anesthesiology grade in the OG group. CONCLUSION: Laparoscopic-assisted radical gastrectomy was relative safe even effective in elderly gastric cancer patients. We should pay attention to the different risk factors when performing different surgical procedures for gastric cancer in elderly patients.


Assuntos
Laparoscopia , Neoplasias Gástricas , Idoso , Gastrectomia , Humanos , Excisão de Linfonodo , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
5.
FASEB J ; 33(10): 11045-11059, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31298933

RESUMO

Various studies demonstrate that long noncoding RNAs (lncRNAs) act as oncogenes or tumor suppressors in cancer. However, the function of lncRNAs in bladder cancer still remains largely unknown. In this study, we identified an lncRNA, gastric cancer-associated lncRNA1 (GClnc1), which was in high abundance in bladder cancer tissues and its expression was related to poor survival rates in patients with bladder cancer. In vitro and in vivo assays showed that GClnc1 significantly promoted cell proliferation, metastasis, and invasiveness in bladder cancer. Mechanistically, we first found that GClnc1 bound to LIN28B and promoted the expression of myelocytomatosis proto-oncogene (MYC) through the LIN28B/let-7a/MYC pathway. In short, GClnc1 is clinically, functionally, and mechanistically oncogenic in bladder cancer. GClnc1 may be a potential target for treating patients with bladder cancer.-Zhuang, C., Ma, Q., Zhuang, C., Ye, J., Zhang, F., Gui, Y. LncRNA GClnc1 promotes proliferation and invasion of bladder cancer through activation of MYC.


Assuntos
Proliferação de Células , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias da Bexiga Urinária/genética , Animais , Linhagem Celular Tumoral , Movimento Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Proto-Oncogene Mas , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
6.
Surg Endosc ; 34(10): 4582-4592, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31741159

RESUMO

BACKGROUND: Sarcopenia is a negative predictor for postoperative recovery. This study was performed to evaluate the short-term outcomes of laparoscopic surgery in colorectal cancer patients with sarcopenia. METHODS: We conducted a study of patients who underwent curative surgeries for colorectal cancer in two centers from July 2014 to July 2018. In order to reduce selection bias, we conducted a propensity score matching analysis. Preoperative characteristics including age, gender, anemia, body mass index, hypoalbuminemia, America society of anesthesiology scores, epidural anesthesia, operative procedure, stoma, tumor location, and combined resection were incorporated in the model, and produced 58 matched pairs. The third lumbar skeletal muscle mass, handgrip strength, and 6 m usual gait speed were measured to define sarcopenia. Short-term outcomes were compared between the two groups. RESULTS: In a total of 1136 patients, 272 had sarcopenia diagnosed, and 227 were further analyzed in this study. Among them, 108 patients underwent laparoscopic colorectal surgery and 119 underwent open colorectal surgery. In the matched cohort, the clinical characteristics of the two groups were well matched. The laparoscopic group had significantly reduced overall complications (15.5% vs. 36.2%, P = 0.016) and shorter postoperative hospital stays (10.5 vs. 14, P = 0.027). Subgroup analysis of postoperative complications showed that the incidence of surgical complications (P = 0.032) was lower in the laparoscopic group. Hospitalization costs (P = 0.071) and 30-day readmissions (P = 0.215) were similar between the two groups. CONCLUSION: Laparoscopic surgery for colorectal cancer is a safe and feasible option with better short-term outcomes in patients with sarcopenia.


Assuntos
Cirurgia Colorretal , Laparoscopia , Cuidados Pós-Operatórios , Sarcopenia/cirurgia , Idoso , Estudos de Coortes , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Incidência , Masculino , Análise Multivariada , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Fatores de Risco , Sarcopenia/complicações , Sarcopenia/diagnóstico , Resultado do Tratamento
7.
J Cell Mol Med ; 23(3): 2163-2173, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30648791

RESUMO

The abundant and reversible N6-methyladenosine (m6A) RNA modification and its modulators have important roles in regulating various gene expression and biological processes. Here, we demonstrate that fat mass and obesity associated (FTO), as an m6A demethylase, plays a critical anti-tumorigenic role in clear cell renal cell carcinoma (ccRCC). FTO is suppressed in ccRCC tissue. The low expression of FTO in human ccRCC correlates with increased tumour severity and poor patient survival. The Von Hippel-Lindau-deficient cells expressing FTO restores mitochondrial activity, induces oxidative stress and ROS production and shows impaired tumour growth, through increasing expression of PGC-1α by reducing m6A levels in its mRNA transcripts. Our work demonstrates the functional importance of the m6A methylation and its modulator, and uncovers a critical FTO-PGC-1α axis for developing effective therapeutic strategies in the treatment of ccRCC.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Transdução de Sinais/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Animais , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Progressão da Doença , Células HEK293 , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Camundongos Nus , Mitocôndrias/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Transplante Heterólogo , Carga Tumoral/genética
8.
Nat Methods ; 13(11): 938-944, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27595406

RESUMO

The complex phenotypes of eukaryotic cells are controlled by decision-making circuits and signaling pathways. A key obstacle to implementing artificial connections in signaling networks has been the lack of synthetic devices for efficient sensing, processing and control of biological signals. By extending sgRNAs to include modified riboswitches that recognize specific signals, we can create CRISPR-Cas9-based 'signal conductors' that regulate transcription of endogenous genes in response to external or internal signals of interest. These devices can be used to construct all the basic types of Boolean logic gates that perform logical signal operations in mammalian cells without needing the layering of multiple genetic circuits. They can also be used to rewire cellular signaling events by constructing synthetic links that couple different signaling pathways. Moreover, this approach can be applied to redirect oncogenic signal transduction by controlling simultaneous bidirectional (ON-OFF) gene transcriptions, thus enabling reprogramming of the fate of cancer cells.


Assuntos
Sistemas CRISPR-Cas/genética , RNA Guia de Cinetoplastídeos/genética , Transdução de Sinais , Ativação Transcricional , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Reprogramação Celular/genética , Redes Reguladoras de Genes/genética , Células HEK293 , Humanos , Camundongos Nus , Neoplasias Experimentais/genética , Plasmídeos , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/genética , Ressonância de Plasmônio de Superfície , Ativação Transcricional/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética
9.
Dig Dis Sci ; 63(6): 1620-1630, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29549473

RESUMO

BACKGROUND: With the increased prevalence of obesity and sarcopenia, those patients with both visceral obesity and sarcopenia were at higher risk of adverse outcomes. AIM: The aim of this study was to ascertain the combined impact of visceral obesity and sarcopenia on short-term outcomes in patients undergoing colorectal cancer surgery. METHODS: We conducted a prospective study from July 2014 to February 2017. Patients' demographic, clinical characteristics, physical performance, and postoperative short-term outcomes were collected. Patients were classified into four groups according to the presence of sarcopenia or visceral obesity. Clinical variables were compared. Univariate and multivariate analyses evaluating the risk factors for postoperative complications were performed. RESULTS: A total of 376 patients were included; 50.8 and 24.5% of the patients were identified as having "visceral obesity" and "sarcopenia," respectively. Patients with sarcopenia and visceral obesity had the highest incidence of total, surgical, and medical complications. Patients with sarcopenia or/and visceral obesity all had longer hospital stays and higher hospitalization costs. Age ≥ 65 years, visceral obesity, and sarcopenia were independent risk factors for total complications. Rectal cancer and visceral obesity were independent risk factors for surgical complications. Age ≥ 65 years and sarcopenia were independent risk factors for medical complications. Laparoscopy-assisted operation was a protective factor for total and medical complications. CONCLUSION: Patients with both visceral obesity and sarcopenia had a higher complication rate after colorectal cancer surgery. Age ≥ 65 years, visceral obesity, and sarcopenia were independent risk factors for total complications. Laparoscopy-assisted operation was a protective factor.


Assuntos
Colectomia , Neoplasias Colorretais/cirurgia , Laparoscopia , Obesidade Abdominal/epidemiologia , Sarcopenia/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , China/epidemiologia , Colectomia/efeitos adversos , Colectomia/economia , Colectomia/métodos , Neoplasias Colorretais/economia , Neoplasias Colorretais/epidemiologia , Comorbidade , Feminino , Custos Hospitalares , Humanos , Incidência , Laparoscopia/efeitos adversos , Laparoscopia/economia , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Obesidade Abdominal/economia , Razão de Chances , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/epidemiologia , Prevalência , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Proteção , Fatores de Risco , Sarcopenia/economia , Fatores de Tempo , Resultado do Tratamento
11.
J Surg Res ; 218: 58-66, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28985878

RESUMO

BACKGROUND: Gastrectomy results in a significant loss of body composition in the long term, but the acute skeletal muscle wasting after gastrectomy has been rarely investigated. Moreover, the association between postoperative muscle wasting and quality of life (QOL) has never been reported. In the present study, we aimed to investigate the risk factors for acute muscle wasting after gastric cancer surgery and its effect on QOL and short-term postoperative outcomes. METHODS: We conducted a prospective study of patients who underwent curative gastrectomy for gastric cancer between June 2015 and December 2015. Skeletal muscle mass was measured by computed tomography within 1 month before and 1 week after surgery. QOL was assessed 1, 3, and 6 months postoperatively. Univariate and multivariate analyses were performed to identify the risk factors for clinically relevant muscle wasting (muscle wasting ≥10%). RESULTS: A total of 110 patients were included, in which 35 patients had muscle wasting ≥10% within 1 week after surgery. Age ≥65 years and diabetes were independent risk factors for muscle wasting ≥10%. Patients with muscle wasting ≥10% had a poorer QOL in terms of fatigue and physical functioning at 1 and 3 months postoperatively, as well as a higher incidence of postoperative complications, a higher incidence of handgrip strength reduction ≥10%, longer hospital stays, and higher costs. CONCLUSIONS: Age ≥65 years and diabetes were independently associated with clinically relevant muscle wasting within 1 week after gastric cancer surgery. Clinically relevant muscle wasting was associated with a poorer QOL and short-term outcomes after surgery.


Assuntos
Atrofia Muscular/etiologia , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Neoplasias Gástricas/cirurgia , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Atrofia Muscular/diagnóstico por imagem , Atrofia Muscular/epidemiologia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
12.
J Surg Res ; 211: 137-146, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28501109

RESUMO

BACKGROUND: A geriatric assessment is needed to identify high-risk elderly patients with gastric cancer. However, the current geriatric assessment has been considered to be either time-consuming or subjective. The present study aimed to investigate the predictive effect of sarcopenia on the postoperative complications for elderly patients who underwent radical gastrectomy. MATERIALS AND METHODS: We conducted a prospective study of patients who underwent radical gastrectomy from August 2014 to December 2015. Computed tomography-assessed lumbar skeletal muscle, handgrip strength, and gait speed were measured to define sarcopenia. RESULTS: Sarcopenia was present in 69 of 240 patients (28.8%) and was associated with lower body mass index, lower serum albumin, lower hemoglobin, and higher nutritional risk screening 2002 scores. Postoperative complications significantly increased in the sarcopenic patients (49.3% versus 24.6%, P < 0.001), compared with nonsarcopenic patients. The multivariate analysis demonstrated that sarcopenia (odds ratio: 2.959, 95% CI: 1.629-5.373, P < 0.001) and the Charlson comorbidity index ≥2 (odds ratio: 3.357, 95% CI: 1.144-9.848, P = 0.027) were independent risk factors for postoperative complications. CONCLUSIONS: Sarcopenia, presented as a new geriatric assessment factor, was a strong and independent risk factor for postoperative complications of elderly patients with gastric cancer.


Assuntos
Carcinoma/cirurgia , Gastrectomia , Avaliação Geriátrica , Complicações Pós-Operatórias/etiologia , Sarcopenia/complicações , Neoplasias Gástricas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma/complicações , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Fatores de Risco , Sarcopenia/diagnóstico , Neoplasias Gástricas/complicações
13.
J Surg Res ; 209: 153-161, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28032552

RESUMO

BACKGROUND: Precise determination of the lymph node status is critical for determining appropriate treatment for early gastric cancer (EGC). This study attempted to establish a simple, effective risk scoring system to predict lymph node metastasis (LNM) in EGC by investigating the relationship between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) and EGC LNM. MATERIALS AND METHODS: We retrospectively reviewed 312 operable patients with EGC. The clinical utility of PLR and NLR was tested by receiver operating characteristic curves. The scoring system was developed using independent risk factors. Finally, 89 EGC patients were collected from prospective database to validate the scoring system's accuracy. RESULTS: The optimal PLR and NLR cut-off values were 106 and 2.97, respectively. High NLR (P = 0.009) and PLR (P = 0.007) values were associated with LNM of EGC in univariate analyses, although only high PLR (P = 0.025) was an independent risk factor in multivariate analyses, together with age (P = 0.009), differentiation (P = 0.017), invasive depth (P < 0.001), and tumor size (P = 0.003). The scoring system's accuracy for retrospective and prospective data was 0.781 (95% confidence interval: 0.721-0.841) and 0.817 (95% confidence interval 0.714-0.920), respectively. CONCLUSIONS: Preoperative PLR and NLR correlate with EGC LNM. Our scoring system is reliable, accurate, and effective in predicting LNM in EGC patients.


Assuntos
Linfonodos/patologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Neoplasias Gástricas/imunologia
14.
Ann Surg Oncol ; 23(2): 556-64, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26668085

RESUMO

BACKGROUND: Sarcopenia is characterized by decreased skeletal muscle plus low muscle strength and/or physical performance. This study was performed to determine the association of sarcopenia with short-term postoperative outcomes after gastrectomy for gastric cancer. METHODS: We conducted a prospective study of 255 consecutive patients with gastric cancer who underwent curative gastrectomy. The sarcopenia elements, including lumbar skeletal muscle index, handgrip strength, and gait speed, were measured before surgery. Patients were followed up after gastrectomy to gain the actual clinical outcomes. Factors contributing to postoperative complications were analyzed by univariate and multivariate analysis. RESULTS: Sarcopenia was present in 32 of 255 patients (12.5 %), and was significantly correlated with advance age, lower body mass index, higher nutritional risk screening (NRS) 2002 score, and lower preoperative serum albumin and hemoglobin. Compared with non-sarcopenic patients, sarcopenic patients had a higher risk of postoperative complications, longer postoperative hospital stay, and more hospital costs. In univariate analysis, sarcopenia (p < 0.001), nutritional risk (NRS 2002 score ≥3; p = 0.003), advanced age (≥75 years; p = 0.014), anemia (p = 0.012), hypoalbuminemia (p = 0.029), and diabetes (p = 0.014) were associated with postoperative complications. Multivariable analysis revealed that sarcopenia (p < 0.001) and diabetes (p = 0.006) were independent predictors of postoperative complications. CONCLUSIONS: Sarcopenia is an independent predictor of postoperative complications in patients with gastric cancer after gastrectomy.


Assuntos
Gastrectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Sarcopenia/complicações , Índice de Gravidade de Doença , Neoplasias Gástricas/cirurgia , Idoso , Feminino , Seguimentos , Força da Mão/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Fatores de Risco , Neoplasias Gástricas/patologia
15.
Tumour Biol ; 37(3): 3115-21, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26427661

RESUMO

Small hairpin RNA (shRNA) can inhibit the malignant phenotypes of tumor cell through ribonucleic acid interference (RNAi). However, it is hardly to be regulated and it may induce few phenotypic changes. Here, we build a type of tetracycline (Tet)-inducible vectors which can achieve regulatable expression of shRNA in a time-dependent manner by using synthetic biology approach. In order to prove the effectiveness of this device, we chose hTERT and Bcl-2 as target genes and test the utility of the device on 5637 and T24 cell lines. The experiments show that the Tet-inducible small hairpin RNA can effectively suppress their target genes and generate anti-cancer effects on both 5637 and T24 cell lines. The device we build not only can inhibit proliferation but also can induce apoptosis and suppress migration of the bladder cancer cell lines 5637 and T24. The Tet-inducible small hairpin RNAs may provide a novel strategy for the treatment of human bladder cancer in the future.


Assuntos
Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Interferente Pequeno/genética , Telomerase/genética , Tetraciclina/farmacologia , Neoplasias da Bexiga Urinária/terapia , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Fenótipo , Neoplasias da Bexiga Urinária/patologia
16.
Langenbecks Arch Surg ; 401(6): 813-22, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27485549

RESUMO

PURPOSE: This study was performed to determine the association of frailty and nutritional status with postoperative complications after total gastrectomy (TG) with D2 lymphadenectomy in patients with gastric cancer. METHODS: Patients undergoing TG with D2 lymphadenectomy for gastric cancer between August 2014 and February 2016 were enrolled. Frailty was evaluated by sarcopenia which was diagnosed by a combination of third lumbar vertebra muscle index (L3 MI), handgrip strength, and 6-m usual gait speed. Nutritional status was evaluated by the nutritional risk screening 2002 (NRS 2002) score. Univariate and multivariate analyses evaluating the risk factors for postoperative complications were performed. RESULTS: A total of 158 patients were analyzed, and 27.2 % developed complications within 30 days of surgery. One patient died within 30 days of the operation. In the univariate analyses, NRS 2002 score ≥3 (OR = 2.468, P = 0.012), sarcopenia (OR = 2.764, P = 0.008), and tumor located at the cardia (OR = 2.072, P = 0.046) were associated with the postoperative complications. Multivariable analysis revealed that sarcopenia (OR = 3.084, P = 0.005) and tumor located at the cardia (OR = 2.347, P = 0.026) were independent predictors of postoperative complications. CONCLUSIONS: This study showed a significant relationship between postoperative complications and geriatric frailty using sarcopenia in patients with gastric cancer after TG with D2 lymphadenectomy. Frailty should be integrated into preoperative risk assessment and may have implications in preoperative decisionmaking.


Assuntos
Gastrectomia/efeitos adversos , Excisão de Linfonodo/efeitos adversos , Estado Nutricional , Complicações Pós-Operatórias/etiologia , Sarcopenia/complicações , Neoplasias Gástricas/cirurgia , Idoso , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Neoplasias Gástricas/complicações , Velocidade de Caminhada
17.
Tumour Biol ; 36(7): 5157-63, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25775949

RESUMO

The mutant promoter of human telomerase reverse transcriptase (hTERT) shows high transcriptional activity in bladder cancer cells. Some up-regulated microRNAs (miRNAs) are reported as oncogenic factors in bladder cancer. Previous studies report that miRNAs can be inhibited by base-pairing interactions. The purpose of this study is to construct a synthetic device driven by mutant hTERT promoter to suppress four up-regulated miRNAs and to verify its effects on phenotypes of bladder cancer cells and human normal cells. Tandem bulged miRNA binding sites targeting oncogenic miRNAs were inserted into the 3' untranslated region (3' UTR) of mutant hTERT promoter-driven Renilla luciferase gene to construct a synthetic tumor-specific device, miRNA sponges. A negative control was generated by using tandem repeated sequences without targeting any known miRNA. Bladder cancer cells (T24, 5637, UM-UC-3) and human fiber cells (HFC) were transfected with devices. Various functional assays were used to detect the effects of this device. The activity of the mutant hTERT promoter detected by luciferase assay was about three times as large as the wild-type hTERT promoter in bladder cancer cells, while it could not be measured in HFC. Other assays indicated that the synthetic device can significantly inhibit cell growth, decrease motility, and induce apoptosis in bladder cancer cells but not in HFC. A synthetic biology platform is employed to construct tumor-specific miRNA sponges that can be used to target oncogenic miRNAs to inhibit the progression of bladder cancer cells without affecting normal cells.


Assuntos
Carcinogênese , Terapia Genética , MicroRNAs/genética , Telomerase/biossíntese , Neoplasias da Bexiga Urinária/genética , Regiões 3' não Traduzidas/genética , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Humanos , MicroRNAs/síntese química , MicroRNAs/uso terapêutico , Regiões Promotoras Genéticas , Telomerase/genética , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia
18.
Tumour Biol ; 36(10): 7685-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25934337

RESUMO

Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs that play important roles in cancer development and progression. Prostate cancer-associated transcript 1 (PCAT-1) is a novel lncRNA that promotes cell proliferation in prostate cancer. We hypothesized that PCAT-1 also have roles in bladder cancer. In this study, we found that PCAT-1 was up-regulated in bladder cancer compared to paired normal urothelium. Cell proliferation inhibition and apoptosis induction were also observed in PCAT-1 small hairpin RNA (shRNA)-transfected bladder cancer T24 and 5637 cells. Our data suggest that PCAT-1 plays oncogenic roles and can be used as a therapeutic target for treating human bladder cancer.


Assuntos
Apoptose/genética , Proliferação de Células/genética , Inativação Gênica/fisiologia , RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/genética , Linhagem Celular Tumoral , Humanos , RNA Interferente Pequeno/genética , Regulação para Cima/genética , Urotélio/patologia
19.
J Surg Res ; 194(1): 114-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25450599

RESUMO

BACKGROUND: Postoperative fatigue (POF) is an important complication that is commonly observed postoperatively and is also one of the most serious obstacles to postoperative convalescence. However, the risk factors for POF have not been fully addressed, and there is no effective method to predict POF. The aim of the present study was to investigate the risk factors for POF and to explore prediction of the degree of POF. METHODS: A prospective observational study was conducted of patients undergoing elective gastrointestinal surgery. Fatigue score, grip strength, length of postoperative hospital stay (LOS), as well as preoperative and intraoperative factors were collected. χ(2) was used to compare categorical variables, and multivariate logistic regression analysis was used to further analyze correlation between POF and preoperative and intraoperative factors. RESULTS: A total of 155 patients were included in our analysis without loss in follow-up. Multivariate logistic regression analysis after adjustment for factors with severe POF in univariate analysis including preoperative fatigue, plasma albumin and hemoglobin level, and cardiopulmonary function demonstrated that old age, gastrectomy, and a nutritional risk screening 2002 score ≥ 3 were associated with a higher relative risk of severe POF. Moreover, laparoscopic-assisted surgery was associated with lower relative risk of severe POF. CONCLUSIONS: Old age, nutritional risk screening 2002 score ≥ 3 and gastrectomy were risk factors for POF in patients undergoing elective gastrointestinal surgery. POF was reduced in laparoscopic-assisted surgery. Consideration of these factors could be important for the prevention and treatment of POF.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Fadiga/etiologia , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Força Muscular , Estudos Prospectivos , Fatores de Risco
20.
Surg Endosc ; 29(8): 2091-100, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25414064

RESUMO

BACKGROUND: Laparoscopic surgery and enhanced recovery after surgery (ERAS) programs were two major improvements for the management of colorectal diseases. The purpose of this systemic review was to examine whether laparoscopic colorectal surgery still improved short-term postoperative outcomes in comparison with open surgery when both groups of patients received ERAS programs. METHODS: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and reference lists of the identified studies were searched to identify randomized clinical trials that compared laparoscopic with open surgery in patients undergoing colorectal resection in the context of ERAS programs. The outcome measures were analyzed, and the quality of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: Five randomized clinical trials encompassing 598 patients were included in the final analysis. Two of them were multicenter trials. The ERAS programs implemented in the five included trials cannot be classified as optimal ERAS programs, but suboptimal ERAS programs. Laparoscopic colorectal surgery significantly reduced total hospital stay (weighted mean difference (WMD) -1.92 days; 95 % confidence interval (CI) -2.61--1.23 days; P < 0.00001) and number of complications (relative risk (RR) 0.78; 95 % CI 0.66-0.94; P = 0.007) compared with open surgery in the setting of ERAS programs. No significant differences were found between groups for primary hospital stay, number of patients with complications, readmission rates, and mortality. The quality of evidence for all outcomes was low-to-moderate on the GRADE scale, and none had high quality. CONCLUSIONS: Laparoscopic colorectal resection significantly reduced total hospital stay and number of complications when compared with open surgery in the setting of suboptimal ERAS programs, but the benefits of laparoscopic colorectal resection remain to be proved within optimal ERAS programs.


Assuntos
Cirurgia Colorretal/normas , Laparoscopia/normas , Doenças do Colo/cirurgia , Cirurgia Colorretal/métodos , Feminino , Humanos , Laparoscopia/métodos , Tempo de Internação , Avaliação de Resultados em Cuidados de Saúde , Período Pós-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Doenças Retais/cirurgia
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