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1.
Asian J Surg ; 46(1): 291-298, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35414459

RESUMO

BACKGROUND: The relationship between thoracic sarcopenia and clinical outcomes in patients underwent coronary artery bypass grafting (CABG) is unclear. This study aims to evaluate whether thoracic sarcopenia has a satisfactory prognostic effect on adverse outcomes after CABG. METHODS: From December 2015 to May 2021, 338 patients who underwent isolated CABG at our institution were recruited in this study. Skeletal muscle area at T12 level acquired by chest computed tomography (CT) was normalized to assess thoracic sarcopenia. Univariate and multivariate analyses were performed to evaluate the risk factors of postoperative complications and overall survival (OS). RESULTS: The prevalence of thoracic sarcopenia in patients underwent CABG was 13.02%. The incidence of total major complication was significantly higher in thoracic sarcopenia group (81.8% vs 61.9%, p = 0.010). Thoracic sarcopenic patients also had longer postoperative hospital stays (p = 0.047), intensive care unit (ICU) stays (p = 0.001), higher costs (p = 0.001) and readmission rates within 30 days of discharge (18.2% vs 4.4%, p = 0.001). Patients without thoracic sarcopenia showed significantly higher OS at the 2-year follow-up period (93.9% vs 72.7%, p<0.001). Multivariate analyses demonstrated that thoracic sarcopenia was significantly and independently associated with postoperative complications and long-term OS after CABG. CONCLUSION: Thoracic sarcopenia is an effective clinical predictor of adverse postoperative complications and long-term OS in patients underwent CABG. Thoracic sarcopenia based on chest CT should be included in preoperative risk assessment of CABG.


Assuntos
Doença da Artéria Coronariana , Sarcopenia , Humanos , Sarcopenia/complicações , Sarcopenia/diagnóstico por imagem , Sarcopenia/epidemiologia , Estudos de Coortes , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Ponte de Artéria Coronária/métodos , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
2.
Front Oncol ; 12: 967675, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36523965

RESUMO

Introduction: Traditional therapeutic approaches for the treatment of advanced non-small-cell lung cancer (NSCLC) are based on chemotherapy. However, the discovery and understanding of oncogenic driver alterations has led to the development of targeted therapies that have substantially improved patient outcomes. Still, to date, there have been no reports of patients with advanced anaplastic lymphoma kinase (ALK)-positive lung cancer achieving clinical complete response (cCR) in the systemic lesion and pathological complete remission (pCR) in primary lung lesion after multiple lines of conversion therapy. Methods: In this case, a 55-year-old man was diagnosed with ALK-positive, stage IV lung adenocarcinoma using immunohistochemistry and next generation sequencing (NGS) tests. Results: Crizotinib and two other ATP-competitive ALK inhibitors, ceritinib and alectinib, were used respectively as first-line, second-line, and third-line therapy. The patient received treatment with crizotinib and achieved partial response (PR), but 5 months later the efficacy was evaluated as progressive disease (PD). Ceritinib was used as the second-line treatment, but the disease progressed 6 months later. Alectinib was used as the third-line treatment, but the efficacy was evaluated as PD. From April 2019 to November 2019, the patient received 4 cycles of induction chemotherapy with pemetrexed/carboplatin/bevacizumab and then switched to pemetrexed/bevacizumab as the fourth-line treatment, and received the fifth line treatment, cetuximab/paclitaxel liposome/nedaplatin, for 1 cycle, but the disease still progressed. Then the patient received the sixth line of treatment, camrelizumab/lorlatinib, for 9 antitumor cycles, resulting in PR. The patient underwent surgery followed by maintenance treatment with lorlatinib and achieved cCR. To our knowledge, this is the first documented case of cCR in a patient with ALK-positive advanced lung adenocarcinoma treated with multiple lines of therapy followed by surgical treatment. Discussion: This case reveals the possible survival benefit of immunotherapy after multiple line treatment in ALK-positive advanced lung adenocarcinoma, indicating that it is possible find new therapeutic targets based on NGS molecular detection and provide precise therapeutic strategies for clinical practice when drug resistance or progression occurs in cancer therapy.

3.
Oxid Med Cell Longev ; 2022: 9159101, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466088

RESUMO

Sarcopenia, featured by the progressive loss of skeletal muscle function and mass, is associated with the impaired function of muscle stem cells (MuSCs) caused by increasing oxidative stress in senescent skeletal muscle tissue during aging. Intact function of MuSCs maintains the regenerative potential as well as the homeostasis of skeletal muscle tissues during aging. Ginsenoside Rb1, a natural compound from ginseng, exhibited the effects of antioxidation and against apoptosis. However, its effects of restoring MuSC function during aging and improving age-related sarcopenia remained unknown. In this study, we investigated the role of Rb1 in improving MuSC function and inhibiting apoptosis by reducing oxidative stress levels. We found that Rb1 inhibited the accumulation of reactive oxygen species (ROS) and protected the cells from oxidative stress to attenuate the H2O2-induced cytotoxicity. Rb1 also blocked oxidative stress-induced apoptosis by inhibiting the activation of caspase-3/9, which antagonized the decrease in mitochondrial content and the increase in mitochondrial abnormalities caused by oxidative stress via promoting the protein expression of genes involved in mitochondrial biogenesis. Mechanistically, it was proven that Rb1 exerted its antioxidant effects and avoided the apoptosis of myoblasts by targeting the core regulator of the nuclear factor-kappa B (NF-κB) signal pathway. Therefore, these findings suggest that Rb1 may have a beneficial role in the prevention and treatment of MuSC exhaustion-related diseases like sarcopenia.


Assuntos
NF-kappa B , Sarcopenia , Humanos , Peróxido de Hidrogênio/toxicidade , Estresse Oxidativo , Mioblastos , Apoptose , Antioxidantes/farmacologia , Músculo Esquelético , Mitocôndrias , Ubiquitina-Proteína Ligases , Proteínas de Ligação a Retinoblastoma
4.
Heart Lung Circ ; 31(10): 1408-1418, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35961821

RESUMO

BACKGROUND: As the proportion of elderly patients increases, higher incidence of malnutrition is found among patients with valvular heart disease. Sarcopaenia is one of the main manifestations of malnutrition. Studies have shown the certain predictive effect of sarcopaenia on the clinical outcome in different cases. This study aims to clarify the impact of computed tomography (CT)-derived thoracic sarcopaenia on clinical outcomes of patients who underwent cardiac valve surgery. METHODS: The clinical data of 216 patients who underwent cardiac valve surgery from December 2015 to June 2020 were retrospectively collected. Skeletal muscle mass at 12th thoracic vertebra level was measured to diagnose thoracic sarcopaenia. Postoperative complications and follow-up data were collected. Medium follow-up was 3.2 years. RESULTS: The prevalence of thoracic sarcopaenia was 16.7% in this study. The incidence of total complications and in-hospital mortality were higher in thoracic sarcopaenia group (p=0.024 and p=0.014, respectively). Multivariate analysis revealed that thoracic sarcopaenia is a significant predictor for postoperative complications (OR 2.319; 95% CI 1.003-5.366; p=0.049). Decreased long-term survival was observed in patients with thoracic sarcopaenia. Thoracic sarcopaenia (HR 4.178; 95% CI 2.062-8.465; p<0.001) was determined to be an independent risk factor for late mortality. CONCLUSION: Thoracic sarcopaenia defined by chest CT was independently associated with higher incidence of postoperative complications and long-term mortality. Routine preoperative evaluation of thoracic sarcopaenia deserves further consideration to enhance the predictive performance for operation risk.


Assuntos
Valvas Cardíacas , Desnutrição , Idoso , Valvas Cardíacas/cirurgia , Humanos , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
5.
Cancer Commun (Lond) ; 42(9): 868-886, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35848447

RESUMO

BACKGROUND: Elucidation of the post-transcriptional modification has led to novel strategies to treat intractable tumors, especially glioblastoma (GBM). The ubiquitin-proteasome system (UPS) mediates a reversible, stringent and stepwise post-translational modification which is closely associated with malignant processes of GBM. To this end, developing novel therapeutic approaches to target the UPS may contribute to the treatment of this disease. This study aimed to screen the vital and aberrantly regulated component of the UPS in GBM. Based on the molecular identification, functional characterization, and mechanism investigation, we sought to elaborate a novel therapeutic strategy to target this vital factor to combat GBM. METHODS: We combined glioma datasets and human patient samples to screen and identify aberrantly regulated E3 ubiquitin ligase. Multidimensional database analysis and molecular and functional experiments in vivo and in vitro were used to evaluate the roles of HECT, UBA and WWE domain-containing E3 ubiquitin ligase 1 (HUWE1) in GBM. dCas9 synergistic activation mediator system and recombinant adeno-associated virus (rAAV) were used to endogenously overexpress full-length HUWE1 in vitro and in glioma orthotopic xenografts. RESULTS: Low expression of HUWE1 was closely associated with worse prognosis of GBM patients. The ubiquitination and subsequent degradation of N-Myc mediated by HUWE1, leading to the inactivation of downstream Delta-like 1 (DLL1)-NOTCH1 signaling pathways, inhibited the proliferation, invasion, and migration of GBM cells in vitro and in vivo. A rAAV dual-vector system for packaging and delivery of dCas9-VP64 was used to augment endogenous HUWE1 expression in vivo and showed an antitumor activity in glioma orthotopic xenografts. CONCLUSIONS: The E3 ubiquitin ligase HUWE1 acts through the N-Myc-DLL1-NOTCH1 signaling axis to suppress GBM progression. Antitumor activity of rAAV dual-vector delivering dCas9-HUWE1 system uncovers a promising therapeutic strategy for GBM.


Assuntos
Glioblastoma , Proteínas Supressoras de Tumor , Ubiquitina-Proteína Ligases , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Glioblastoma/genética , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo , Transdução de Sinais , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
6.
J Clin Invest ; 132(5)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35229723

RESUMO

Cancer stem-like cells (CSLCs) acquire enhanced immune checkpoint responses to evade immune cell killing and promote tumor progression. Here we showed that signal regulatory protein γ (SIRPγ) determined CSLC properties and immune evasiveness in a small population of lung adenocarcinoma (LUAD) cancer cells. A SIRPγhi population displayed CSLC properties and transmitted the immune escape signal through sustaining CD47 expression in both SIRPγhi and SIRPγlo/- tumor cells. SIRPγ bridged MST1 and PP2A to facilitate MST1 dephosphorylation, resulting in Hippo/YAP activation and leading to cytokine release by CSLCs, which stimulated CD47 expression in LUAD cells and consequently inhibited tumor cell phagocytosis. SIRPγ promoted tumor growth and metastasis in vivo through YAP signaling. Notably, SIRPγ targeting with genetic SIRPγ knockdown or a SIRPγ-neutralizing antibody inhibited CSLC phenotypes and elicited phagocytosis that suppressed tumor growth in vivo. SIRPG was upregulated in human LUAD and its overexpression predicted poor survival outcome. Thus, SIRPγhi cells serve as CSLCs and tumor immune checkpoint-initiating cells, propagating the immune escape signal to the entire cancer cell population. Our study identifies Hippo/YAP signaling as the first mechanism by which SIRPγ is engaged and reveals that targeting SIRPγ represents an immune- and CSLC-targeting strategy for lung cancer therapy.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/metabolismo , Antígeno CD47/genética , Antígeno CD47/metabolismo , Linhagem Celular Tumoral , Via de Sinalização Hippo , Humanos , Neoplasias Pulmonares/genética , Transdução de Sinais
7.
Free Radic Biol Med ; 178: 59-75, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34823019

RESUMO

The progressive and generalized loss of skeletal muscle mass and function, also known as sarcopenia, underlies disability, increasing adverse outcomes and poor quality of life in older people. Exercise interventions are commonly recommended as the primary treatment for sarcopenia. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a vital role in regulating metabolism, mitochondrial function, and the ROS-dependent adaptations of skeletal muscle, as the response to exercise. To investigate the contribution of Nrf2 to the benefits of exercise interventions in older age, aged (∼22 month old) Nrf2 knockout (Nrf2-KO) mice and age-matched wild-type (WT) C57BL6/J mice were randomly divided into 2 groups (sedentary or exercise group). We found that exercise interventions improved skeletal muscle function and restored the sarcopenia-like phenotype in WT mice, accompanied with the increasing mRNA level of Nrf2. While these alternations were minimal in Nrf2-KO mice after exercise. Further studies indicated that Nrf2 could increase the stability of Drp1 through deubiquitinating and promote Drp1-dependent mitochondrial fission to attenuate mitochondrial disorder. We also observed the effects of sulforaphane (SFN), a Nrf2 activator, in restoring mitochondrial function in senescent C2C12 cells and improving sarcopenia in older WT mice, which were abolished by Nrf2 deficiency. These results indicated that some benefits of exercise intervention to skeletal muscle were Nrf2 mediated, and a future work should focus on Nrf2 signaling to identify a pharmacological treatment for sarcopenia.


Assuntos
Dinâmica Mitocondrial , Fator 2 Relacionado a NF-E2 , Animais , Camundongos , Terapia por Exercício , Músculo Esquelético , Fator 2 Relacionado a NF-E2/genética , Envelhecimento , Condicionamento Físico Animal
8.
Drug Deliv ; 28(1): 1548-1561, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34286631

RESUMO

PURPOSE: Tumor RNA vaccines can activate dendritic cells to generate systemic anti-tumor immune response. However, due to easily degraded of RNA, direct RNA vaccine is less effective. In this study, we optimized the method for preparing PEGylated liposom-polycationic DNA complex (LPD) nanoliposomes, increased encapsulate amount of total RNA derived from CT-26 colorectal cancer cells. Tumor RNA LPD nanoliposomes vaccines improved anti-tumor immune response ability of tumor RNA and can effectively promote anti-tumor therapeutic effect of oxaliplatin. METHODS: Total tumor-derived RNA was extracted from colorectal cancer cells (CT-26 cells), and loaded to our optimized the LPD complex, resulting in the LPD nanoliposomes. We evaluated the characteristics (size, zeta potential, and stability), cytotoxicity, transfection ability, and tumor-growth inhibitory efficacy of LPD nanoliposomes. RESULTS: The improved LPD nanoliposomes exhibited a spherical shape, RNA loading efficiency of 9.07%, the average size of 120.37 ± 2.949 nm and zeta potential was 3.34 ± 0.056 mV. Also, the improved LPD nanoliposomes showed high stability at 4 °C, with a low toxicity and high cell transfection efficacy toward CT-26 colorectal cancer cells. Notably, the improved LPD nanoliposomes showed tumor growth inhibition by activating anti-tumor immune response in CT-26 colorectal cancer bearing mice, with mini side effects toward the normal organs of mice. Furthermore, the effect of the improved LPD nanoliposomes in combination with oxaliplatin can be better than that of oxaliplatin alone. CONCLUSION: The improved LPD nanoliposomes may serve as an effective vaccine to induce antitumor immunity, presenting a new treatment option for colorectal cancer.


Assuntos
Antineoplásicos/farmacologia , Vacinas Anticâncer/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Nanopartículas/química , Oxaliplatina/farmacologia , RNA/administração & dosagem , Animais , Linfócitos T CD8-Positivos/citologia , Vacinas Anticâncer/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular , Química Farmacêutica , Portadores de Fármacos/química , Estabilidade de Medicamentos , Quimioterapia Combinada , Lipossomos/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Polietilenoglicóis/química , RNA/farmacologia , Propriedades de Superfície , Transfecção
9.
Biomed Eng Online ; 20(1): 67, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217312

RESUMO

Hepatocellular carcinoma (HCC) is currently the sixth most common malignancy and the second major cause of tumor-related deaths in the world. This study aimed to investigate the role of cleavage and polyadenylation factor-6 (CPSF6) and B-cell translocation gene 2 (BTG2) in regulating the glycolysis and apoptosis in HCC cells. The RNA and protein expression of CPSF6 and BTG2 in normal hepatocyte and HCC were, respectively, detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis and Western blot analysis. The viability and apoptosis of transfected Huh-7 cells were, respectively, analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay. The expression of apoptosis-related proteins and HK-2 in transfected Huh-7 cells was also detected by Western blot analysis. The levels of glucose and lactate in the culture supernatant of transfected Huh-7 cells were, respectively, detected with the glucose assay kit and lactate assay kit. The interaction of CPSF6 and BTG2 was confirmed by RNA binding protein immunoprecipitation (RIP) assay. As a result, CPSF6 expression was increased while BTG2 expression was decreased in Huh-7 cells. Interference with CPSF6 suppressed the viability and glycolysis, and promoted the apoptosis of Huh-7 cells. Furthermore, CPSF6 interacted with BTG2 and interference with CPSF6 upregulated the BTG2 expression and inhibited the protein kinase B (AKT)/extracellular signal-regulated kinase (ERK)/nuclear factor (NF)-κB pathway. Interference with BTG2 could partially reverse the above cell changes caused by interference with CPSF6. In conclusion, CPSF6 inhibited the BTG2 expression to promote glycolysis and suppress apoptosis in HCC cells by activating AKT/ERK/NF-κB pathway.


Assuntos
Carcinoma Hepatocelular , Proteínas Imediatamente Precoces , Neoplasias Hepáticas , Apoptose , Carcinoma Hepatocelular/genética , Proteínas de Transporte , Linhagem Celular Tumoral , Proliferação de Células , Glicólise , Humanos , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Neoplasias Hepáticas/genética , RNA , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Fatores de Poliadenilação e Clivagem de mRNA
10.
Eur J Surg Oncol ; 47(8): 1976-1984, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33714648

RESUMO

BACKGROUND: Patients with gastric cancer often suffer from generalized and progressive reduction of skeletal muscle mass and strength, which negatively affects the quality of life (QOL). In this study, we explored the impact of sarcopenia on QOL and overall survival (OS). METHODS: From December 2015 to June 2017, 135 patients underwent radical gastrectomy at the First Affiliated Hospital of Wenzhou Medical University. Based on the diagnostic criteria of the Asian Working Group for Sarcopenia (AWGS), data including handgrip strength, 6-m gait speed and muscle mass were collected and analyzed. EORTC QLQ-C30 and EORTC QLQ-STO22 were used to evaluate the QOL before surgery, 1, 3 and 6 months after surgery. RESULTS: A total of 27 out of the 135 patients (20.00%) were diagnosed with sarcopenia. Compared with non-sarcopenia group, patients in sarcopenia group had a higher incidence of postoperative complications (14.80% vs. 40.70%, p = 0.003), and more hospitalization costs (p = 0.029). The scores of eating restriction (p = 0.026), anxiety (p = 0.045) and body image (p = 0.046) were significantly higher in sarcopenia group at postoperative 6 months. Besides, sarcopenia was an independent risk factor for global health status at 6 months after operation (OR: 2.881, 95% CI: 1.110-7.475, p = 0.030) and OS (HR: 3.140, 95% CI: 1.255-7.855, p = 0.014). Other factors, including tumor stage III and the postoperative complications, had negative influences on OS. CONCLUSION: Sarcopenia is a predictive factor of poor QOL and prognosis in patients with gastric cancer.


Assuntos
Adenocarcinoma/cirurgia , Gastrectomia , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Sarcopenia/epidemiologia , Neoplasias Gástricas/cirurgia , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Ansiedade/epidemiologia , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Taxa de Sobrevida
11.
Nutrition ; 84: 111044, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33517155

RESUMO

OBJECTIVES: The aim of this study was to determine the feasibility of substituting handgrip strength (HGS) for muscle mass as a constituent in the Global Leadership Initiative on Malnutrition (GLIM) to diagnose malnourished patients with gastrointestinal (GI) cancer. METHODS: The study included 2209 patients diagnosed with GI cancer from two centers. All patients were evaluated for nutritional risk using Nutritional Risk Screening 2002 within 24 h of admission. The GLIM consensus was then used to diagnose malnourished patients. The evaluation of muscle mass as one of the constituents contained in the GLIM consensus was measured by computed tomography presented as skeletal muscle mass index (SMI) and HGS, respectively. Consistency test was carried out to evaluate the diagnostic value of SMI and HGS. RESULTS: There were 1042 (47.2%) cases of gastric cancer and 1167 (52.8%) cases of colorectal cancer. Among these cases were 768 patients (34.8%) at nutritional risk. Furthermore, 603 (27.3%) and 593 patients (26.8%) were diagnosed with malnutrition in the GLIM (SMI) group and the GLIM (HGS) group, respectively, and 544 (24.6%) patients in the two groups overlapped. The consistency test results showed that the κ value in the GLIM (HGS) group compared with the GLIM (SMI) group was 0.881 (P < 0.001) in patients with gastric cancer and 0.872 (P < 0.001) in those with colorectal cancer. CONCLUSION: HGS can be a substitute for muscle mass as a constituent in the diagnostic criteria of GLIM in patients with GI cancer.


Assuntos
Neoplasias Gastrointestinais , Desnutrição , Estudos de Viabilidade , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/diagnóstico , Força da Mão , Humanos , Liderança , Desnutrição/diagnóstico , Músculo Esquelético
12.
Clin Nutr ; 40(5): 3360-3369, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33223117

RESUMO

BACKGROUND: Few studies have comprehensively analyzed the correlations among body composition parameters, muscle strength, and physical performance, as well as the influence of these factors on the postoperative complications and survival after radical gastrectomy for gastric cancer. METHODS: A prospective study was conducted including patients who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral fat area (VFA), subcutaneous fat area (SFA) was obtained by measurement of preoperative computed tomography (CT) images. Grip strength and 6-m gait speed were measured to assess muscle strength and physical performance before surgery. RESULTS: There was a positive correlation between SMI and SMD, as well as between SFA and VFA. SMD negatively correlated with SFA and VFA. SMI had a positive correlation with VFA, but showed minimal correlation with SFA and visceral to subcutaneous fat ratio (VSR). Grip strength and gait speed were both positively correlated with SMI and SMD, but showed minimal correlation with SFA, VFA and VSR. SMI and grip strength independently predicted postoperative complications, rather than SMD or gait speed. Whereas SMD and gait speed had independent predictive value for overall survival (OS) and/or disease-free survival (DFS), rather than SMI or grip strength. VSR independently predicted postoperative complications, rather than VFA or SFA alone. Low SFA was an independent risk factor for OS and DFS. High VFA was associated with worse survival in overweight patients (body mass index, BMI ≥25), but was associated with better survival in non-overweight patients (BMI <25). High SFA did not significantly influence survival in overweight patients, but was associated with better survival in non-overweight patients. CONCLUSION: There is an extensive and complex correlation among body composition parameters, grip strength, and gait speed in patients with operable gastric cancer. A comprehensive analysis of these parameters has significant predictive value for postoperative complications and survival.


Assuntos
Composição Corporal/fisiologia , Gastrectomia , Força Muscular/fisiologia , Complicações Pós-Operatórias/epidemiologia , Neoplasias Gástricas , Idoso , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Desempenho Físico Funcional , Estudos Prospectivos , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/cirurgia
13.
J Exp Clin Cancer Res ; 39(1): 274, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33280610

RESUMO

BACKGROUND: The identification of novel targets for recovering sorafenib resistance is pivotal for Hepatocellular carcinoma (HCC) patients. Mitophagy is the programmed degradation of mitochondria, and is likely involved in drug resistance of cancer cells. Here, we identified hyperactivated mitophagy is essential for sorafenib resistance, and the mitophagy core regulator gene ATAD3A (ATPase family AAA domain containing 3A) was down regulated in hypoxia induced resistant HCC cells. Blocking mitophagy may restore the sorafenib sensitivity of these cells and provide a new treatment strategy for HCC patients. METHODS: Hypoxia induced sorafenib resistant cancer cells were established by culturing under 1% O2 with increasing drug treatment. RNA sequencing was conducted in transfecting LM3 cells with sh-ATAD3A lentivirus. Subsequent mechanistic studies were performed in HCC cell lines by manipulating ATAD3A expression isogenically where we evaluated drug sensitivity, molecular signaling events. In vivo study, we investigated the combined treatment effect of sorafenib and miR-210-5P antagomir. RESULTS: We found a hyperactivated mitophagy regulating by ATAD3A-PINK1/PARKIN axis in hypoxia induced sorafenib resistant HCC cells. Gain- and loss- of ATAD3A were related to hypoxia-induced mitophagy and sorafenib resistance. In addition, ATAD3A is a functional target of miR-210-5p and its oncogenic functions are likely mediated by increased miR-210-5P expression. miR-210-5P was upregulated under hypoxia and participated in regulating sorafenib resistance. In vivo xenograft assay showed that miR-210-5P antagomir combined with sorafenib abrogated the tumorigenic effect of ATAD3A down-regulation in mice. CONCLUSIONS: Loss of ATAD3A hyperactivates mitophagy which is a core event in hypoxia induced sorafenib resistance in HCC cells. Targeting miR-210-5P-ATAD3A axis is a novel therapeutic target for sorafenib-resistant HCC.


Assuntos
ATPases Associadas a Diversas Atividades Celulares/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Sorafenibe/farmacologia , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitofagia/efeitos dos fármacos , Hipóxia Tumoral/fisiologia
14.
J Phys Condens Matter ; 33(9): 095001, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33246323

RESUMO

As a third-generation semiconductor, silicon carbide power devices are expected to be superior to those made of silicon because of their high voltage resistance, low loss, and high efficiency. So understanding the technology for polishing wafers of silicon carbide is important, which includes studying the structure of the liquid on the surface of silicon carbide. Using molecular dynamics based on Lennard-Jones field, the structure of a water film contained within two silicon carbide (〈001〉 and 〈110〉) walls was analyzed, and found that layers of water appear and change depending on the distance between the two walls. When a double-layer water structure forms, it is affected by the temperature and shear velocity. The conclusion is that when the temperature increases or the shear velocity increases, the double-layer water structure easily transforms into a single-layer water structure, and the pressure between the two solid surfaces gradually falls and may even become negative. This phenomenon significantly depends on the distance between the two silicon carbide walls.

15.
Clin Nutr ; 39(7): 2301-2310, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31732287

RESUMO

BACKGROUND: In 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) reached a consensus on sarcopenia (EWGSOP1). In 2018, the EWGSOP met again (EWGSOP2) to update original definition of sarcopenia. This study aimed to investigate the association of sarcopenia and survival and compare the prognostic effects of sarcopenia as defined by EWGSOP1 and EWGSOP2 after gastrectomy. METHODS: We conducted a prospective study including patients who underwent curative gastrectomy for gastric cancer from August 2014 to February 2018. The sarcopenia elements, including skeletal muscle index, muscle attenuation, handgrip strength, and gait speed were measured before surgery. Patients were followed up after gastrectomy to gain the actual clinical outcomes. RESULTS: The prevalence of sarcopenia was 17.0% and 18.9% according to the EWGSOP1 and EWGSOP2 respectively. Sarcopenia was independent risk factor for postoperative complications. Compared with EWGSOP1-sarcopenia, EWGSOP2-sarcopenia and had a higher odds ratio (OR) (2.453 vs. 1.550) in multivariate model. Area under the ROC curve of model including EWGSOP2-sarcopenia was larger than that of the model including EWGSOP1-sarcopenia (AUC 0.653 vs. 0.634, P = 0.021). For both of EWGSOP1 and EWGSOP2, sarcopenia was an independent risk factor for overall survival (OS) and disease-free survival (DFS), but EWGSOP2-sarcopenia seemed to have a higher hazard ratio (OS, 1.667 vs. 1.449; DFS, 1.603 vs. 1.563). In addition, severe sarcopenia, as defined by either EWGSOP2 or EWGSOP1, had a strong predictive power (OR 4.909 vs. 3.827) for postoperative complications. Both versions of severe sarcopenia were significantly predictive of OS and DFS in Cox analysis. CONCLUSION: Sarcopenia at uniform diagnosis standard was an independent risk factor for survival in patients undergoing radical gastrectomy for gastric cancer. Sarcopenia defined by EWGSOP2 criteria better predicts clinical outcomes than that defined by EWGSOP1 criteria in patients with gastric cancer after gastrectomy.


Assuntos
Técnicas de Apoio para a Decisão , Gastrectomia , Músculo Esquelético/diagnóstico por imagem , Sarcopenia/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Intervalo Livre de Doença , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/mortalidade , Força da Mão , Humanos , Masculino , Músculo Esquelético/fisiopatologia , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Sarcopenia/complicações , Sarcopenia/mortalidade , Sarcopenia/fisiopatologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Fatores de Tempo
16.
Cell Death Dis ; 10(3): 148, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30770798

RESUMO

Mitochondrial pyruvate carrier 1 (MPC1), a key factor that controls pyruvate transportation in the mitochondria, is known to be frequently dysregulated in tumor initiation and progression. However, the clinical relevance and potential molecular mechanisms of MPC1 in lung adenocarcinoma (LAC) progression remain to be illustrated. Herein, MPC1 was lowly expressed in LAC tissues and significantly associated with favorable survival of patients with LAC. Functionally, MPC1 markedly suppressed stemness, invasion, and migration in vitro and spreading growth of LAC cells in vivo. Further study revealed that MPC1 could interact with mitochondrial signal transducer and activator of transcription 3 (mito-STAT3), disrupting the distribution of STAT3 and reducing cytoplasmic signal transducer and activator of transcription 3 (cyto-STAT3) as well as its phosphorylation, while the activation of cyto-STAT3 by IL-6 reversed the attenuated malignant progression in MPC1-overexpression LAC cells. Collectively, we reveal that MPC1/STAT3 axis plays an important role in the progression of LAC, and our work may promote the development of new therapeutic strategies for LAC.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Progressão da Doença , Neoplasias Pulmonares/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/deficiência , Transportadores de Ácidos Monocarboxílicos/deficiência , Fator de Transcrição STAT3/metabolismo , Células A549 , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Animais , Movimento Celular/genética , Estudos de Coortes , Feminino , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Invasividade Neoplásica/genética , Taxa de Sobrevida , Transfecção , Carga Tumoral/genética
17.
Lab Invest ; 99(2): 191-199, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30291323

RESUMO

Invasion and subsequent metastasis are major characteristics of malignant human renal cell carcinoma (RCC), though the mechanisms remain elusive. Mitochondrial pyruvate carrier (MPC), a key factor that controls pyruvate transportation in mitochondria, is frequently dysregulated in tumor cells and loss of MPC predicts poor prognosis in various types of cancer. However, the clinical relevance and functional significance of MPC in RCC remain to be elucidated. In this study, we investigated the expression of MPC1 and MPC2 in specimens from RCC patients and observed downregulation of MPC1, but not MPC2, in RCC tissues compared with adjacent non-cancerous tissue. Moreover, RCC patients with higher MPC1 expression exhibited longer overall survival rate than those with lower MPC1. Functionally, MPC1 suppressed the invasion of RCC cells in vitro and reduced the growth of RCC cells in vivo, possibly through inhibition of MMP7 and MMP9. Further studies revealed that loss of MPC1 was induced by hypoxia in RCC cells, and notably, MPC1 expression, was negatively correlated with HIF1α expression in RCC cells and patient samples. Taken together, our results identify anti-tumor function of MPC1 in RCC and revealed MPC1 as a novel prognostic biomarker to predict better patient survival.


Assuntos
Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Animais , Carcinoma de Células Renais/diagnóstico , Hipóxia Celular , Linhagem Celular , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Rim/metabolismo , Neoplasias Renais/diagnóstico , Metaloproteinases da Matriz/análise , Metaloproteinases da Matriz/metabolismo , Camundongos , Camundongos SCID , Proteínas de Transporte da Membrana Mitocondrial/análise , Transportadores de Ácidos Monocarboxílicos , Neoplasias Experimentais , Prognóstico
18.
Am J Cancer Res ; 8(5): 866-878, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29888108

RESUMO

The dysregulation of transcription factors plays a vital role in tumor initiation and progression. Sex determining region Y-box 5 (SOX5) encodes a member of the SRY-related HMG-box family of transcription factors involved in the determination of the cell fate and the regulation of embryonic development. However, its functional roles in non-small cell lung cancer (NSCLC) remain unclear. Herein, we report that SOX5 sustains stem-like traits and enhances the malignant phenotype of NSCLC cells. We determine that SOX5 is preferentially expressed by cancer stem-like cells (CSLCs) of human NSCLC. In vitro gain- and loss-of-function studies demonstrate that SOX5 promotes self-renewal, invasion and migration in NSCLC cells. Importantly, knockdown of SOX5 potently inhibits tumor growth in a xenograft mouse model. Mechanistically, YAP1 can act as an interacting protein of SOX5 to drive the malignant potential of NSCLC cells. Silencing of YAP1 attenuates the malignant processes in NSCLC cells, which is consistent with the function of SOX5 loss. SOX5 overexpression reverses the attenuated malignant progression in YAP1 knockdown cancer cells. Taken together, these findings identify that SOX5 acts as an oncogenic factor by interacting with YAP1 in NSCLC cells and may be a potential therapeutic target for NSCLC patients.

19.
ISA Trans ; 67: 215-221, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27939567

RESUMO

Proportional-integral-derivative (PID) control is widely used in industry because of its simple structure and convenient implementation. However, PID control is suitable for small time delay systems; while if too large delay is encountered, PID control may not obtain the desired performance. Proportional-integral-proportional-derivative (PI-PD) control is a modified of PID control and can get improved control performance; however, due to the complex controller parameter tuning, the PI-PD control is used in a limited scope. Inspired by the advantage of predictive functional control (PFC), a new PI-PD control design using PFC optimization is proposed in this paper. The proposed method not only inherits the advantage of PFC, which does well in coping with the time delay, but also has the same structure as the PI-PD controller. The proposed method is tested on the preheated temperature control of crude oil in a fluidized catalytic cracking unit. The results show that the proposed controller improves control performance compared with typical PID control and PI-PD control.

20.
Zhongguo Fei Ai Za Zhi ; 19(11): 778-783, 2016 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-27866522

RESUMO

As the leading cause of morbidity and cancer related-death worldwide, lung cancer has a serious threat to human health. Exosomes are nanoscale lipid membrane vesicles derived from multivesicles, which containing active biomolecules including proteins, lipids, nucleic acids and etc. Exosomes play important roles in lung cancer initiation and progression by promoting the formation of tumor microenvironment, enhancing tumor invasive and metastasis capability, leading to immunosuppression and resistance to chemoradiotherapy, and also have the application value in early diagnosis and treatment. This review summarizes the research progress of exosomes in tumor initiation and progression, and its roles in diagnosis and treatment of lung cancer.


Assuntos
Exossomos/metabolismo , Neoplasias Pulmonares/metabolismo , Progressão da Doença , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Microambiente Tumoral
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