Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 56
Filtrar
1.
Medicine (Baltimore) ; 99(40): e22505, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019449

RESUMO

RATIONALE: Neuroblastoma (NB) can occur in any part of the sympathetic nervous system, and it is highly heterogeneous. Tumors that only involve bone marrow and bone lesions without solid masses have rarely been reported. PATIENT CONCERNS: A 2-year-old girl child presented with recurrent fever, accompanied by pain in both lower limbs for more than 1 month. DIAGNOSE: Bone marrow examination revealed NB cell invasion. Femoral and multiple vertebral lesions were observed by MRI, while head MRI, chest CT, abdominal CT, and pelvic CT showed no solid mass. INTERVENTIONS: The child received the standard therapy for high-risk NB. OUTCOMES: She was sensitive to the initial chemotherapy protocol. Two years later, a bone marrow examination confirmed NB recurrence. LESSONS: The prognosis of this special type of NB was not improved mainly based on common chemotherapy and local radiotherapy, and new treatment strategies should be explored.


Assuntos
Medula Óssea/patologia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Neuroblastoma/patologia , Exame de Medula Óssea , Neoplasias Ósseas/diagnóstico , Pré-Escolar , Feminino , Humanos , Imagem por Ressonância Magnética , Neuroblastoma/diagnóstico , Tomografia Computadorizada por Raios X
2.
Oncoimmunology ; 9(1): 1806009, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32923168

RESUMO

The tumoricidal efficiency of human CAR-T cells is generally evaluated using immune-deficient mouse models; however, due to their immune-incompetency and the species-specific reactivity of a target antigen, these models are problematic to imitate CAR-T-induced adverse effects in the clinic. Epithelial cell adhesion molecule (EpCAM) is a tumor-associated antigen overtly presented on the cell surface of various carcinomas, making it an attractive target for CAR-T therapy. Here, we developed an anti-mouse EpCAM CAR to evaluate its safety and efficacy in immunocompetent mouse models. As previously reported for their human equivalents, murine EpCAM CAR-T cells exhibit promising anti-tumor efficacy in vitro and in vivo. However, after CAR-T infusion, various dose-depended toxicities including body weight loss, cytokine-release syndrome (CRS), and death were observed in both tumor-bearing and tumor-free mice. Pathological examination revealed unexpected and severe pulmonary immunopathology due to basal EpCAM expression in normal lung. While our study validates EpCAM CAR-T's potent anti-tumor efficacy, it also reveals that EpCAM CAR-T cells used for the treatment of solid tumors may cause lethal toxicity and should, therefore, be evaluated in patients with caution.

3.
J Clin Lab Anal ; 34(10): e23566, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32914892

RESUMO

BACKGROUND: Declared as pandemic by WHO, the coronavirus disease 2019 (COVID-19) pneumonia has brought great damage to human health. The uncontrollable spread and poor progression of COVID-19 have attracted much attention from all over the world. We designed this study to develop a prognostic nomogram incorporating Prognostic nutritional index (PNI) in COVID-19 patients. METHODS: Patients confirmed with COVID-19 and treated in Renmin Hospital of Wuhan University from January to February 2020 were included in this study. We used logistic regression analysis to find risk factors of mortality in these patients. A prognostic nomogram was constructed and receiver operating characteristics (ROC) curve was drawn to evaluate the predictive value of PNI and this prognostic model. RESULTS: Comparison of baseline characteristics showed non-survivors had higher age (P < .001), male ratio (P = .038), neutrophil-to-lymphocyte ratio (NLR) (P < .001), platelet-to-lymphocyte ratio (PLR) (P < .001), and PNI (P < .001) than survivors. In the multivariate logistic regression analysis, independent risk factors of mortality in COVID-19 patients included white blood cell (WBC) (OR 1.285, P = .039), PNI (OR 0.790, P = .029), LDH (OR 1.011, P < .015). These three factors were combined to build the prognostic model. Area under the ROC curve (AUC) of only PNI and the prognostic model was 0.849 (95%Cl 0.811-0.888) and 0.950 (95%Cl 0.922-0.978), respectively. And calibration plot showed good stability of the prognostic model. CONCLUSION: This research indicates PNI is independently associated with the mortality of COVID-19 patients. Prognostic model incorporating PNI is beneficial for clinicians to evaluate progression and strengthen monitoring for COVID-19 patients.


Assuntos
Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Inflamação/fisiopatologia , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Adulto , Idoso , Betacoronavirus , China , Estudos de Coortes , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Prognóstico , Fatores de Risco , Sensibilidade e Especificidade
5.
Medicine (Baltimore) ; 99(25): e20853, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569234

RESUMO

INTRODUCTION: Neuroblastoma (NB) with MYCN amplification has a poor prognosis and high mortality. The potential molecular biological relationship between clinical features and MYCN amplification should be explored. METHODS: NB patients were examined by fluorescence in situ hybridization (FISH) for MYCN amplification in the tumor mass or bone marrow samples to determine whether MYCN was amplified. A series of eleven MYCN-amplified NB patients were included. The age, primary site, tumor size, specific biomarkers, and invaded organs were analyzed. All patients accepted standardized treatment of surgery, chemotherapy, and radiotherapy. Progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: The median age at diagnosis was 24 months. Nine patients (81.8%) were in stage IV, with high serum neuron-specific enolase (NSE) expression, normal urine vanillylmandelic acid (VMA) level and extensive metastases. All patients accepted a chemotherapy protocol with 8 to 10 cycles, and 9 patients (81.8%) were sensitive to the initial chemotherapy protocol. At the end of follow-up, four patients (36.3%) died with a median OS of 15 months. Five patients (45%) survived with a median PFS of 13 months. Two patients were still receiving chemotherapy. CONCLUSION: Given the effect of MYCN amplification on poor outcome in NB, novel treatments targeting MYCN should be developed for patients with NB.


Assuntos
Proteína Proto-Oncogênica N-Myc/metabolismo , Neuroblastoma/patologia , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , Neuroblastoma/metabolismo , Neuroblastoma/mortalidade , Neuroblastoma/terapia , Análise de Sobrevida
7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(3): 416-421, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32543153

RESUMO

Objective: To study the association of glucose variability and ICU delirium of patients after liver transplantation. Methods: This was a retrospective, single-center cohort study. Patients who admitted to ICU after liver transplantation during Aug. 2016 to Dec. 2018 were enrolled. They were divided into two groups accoding to whether they had delirium in ICU. Multivariate logistic regression analysis model was used to analyze the relationship between glucose variability and ICU delirium, and Cochran-Armitage trend test was used to analyze the linear relationship between blood glucose variability levels and the incidence of delirium. Results: A total of 242 patients were enrolled, among them, 36 patients had delirium. The occurrence rate of delirium was 14.9% (36/242). Results indicated that glucose variability was an independently risk factor of ICU delirium for liver transplant patients ( P=0.045), and delirium was more common in patients with higher glucose variability (fourth quartile vs. first quartile, odds ratio =5.283, 95% confidence interval: 1.092~25.550, P=0.038). Results of Cochran-Armitage trend test indicated that there was a linear relationship between blood glucose variability level and ICU delirium rate, with the increase of glucose variability level, the risk of ICU delirium was increased too ( P<0.001). Conclusion: Glucose variability was an independently risk factor of ICU delirium in liver transplantation patients.


Assuntos
Glicemia , Delírio , Transplante de Fígado , Estudos de Coortes , Delírio/epidemiologia , Delírio/etiologia , Humanos , Unidades de Terapia Intensiva , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
9.
BMC Gastroenterol ; 20(1): 164, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460705

RESUMO

BACKGROUND: Patients with acute pancreatitis usually exhibit dyslipidemia and oxidative stress. However, the significance of high-density lipoprotein cholesterol (HDL-C) level, low-density lipoprotein cholesterol (LDL-C) level and the HDL-C/LDL-C ratio (H/L ratio) as markers for disease progression remain unknown. AIM: The aim of this study was to evaluate the role of HDL-C levels, LDL-C levels and the H/L ratio as markers of disease progression in patients admitted to the intensive cate unit with acute pancreatitis. METHODS: This retrospective study was conducted at a tertiary critical care center in China. Plasma HDL-C and LDL-C levels were measured in 166 patients with acute pancreatitis. The associations between HDL-C, LDL-C, H/L ratio, as well as other inflammatory index and mortality, were analyzed. Multivariate cox analysis based on two models was used to determine the independent prognostic factor. Predictive ability of in-hospital mortality for variables was determined using the receiver operating characteristics curves. RESULTS: Significantly higher H/L ratios at admission were observed in patients with acute pancreatitis who died compared with survivors (0.93 vs. 0.64, p < 0.001). The area under the ROC curve for H/L ratio-based prediction of mortality was 0.658. When clinical confounders were included in multivariable cox regression analysis, the association was preserved (Model A HR = 1.587, p = 0.011; Model B HR = 1.332, p = 0.032). The mortality risk in different groups defined by an H/L ratio cutoff value was significantly different, based on survival curve analysis. CONCLUSION: The H/L ratio at the time of admission to the ICU appears to be a biomarker of disease progression in patients with acute pancreatitis.

14.
Int J Pharm ; 576: 118999, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31893541

RESUMO

Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. Moreover, metastasis is one of the main causes of death in CRC patients. Nanotechnology-based gene therapy has shown significant therapeutic benefits in recent clinical trials for cancer treatment. Recent studies have shown that pigment epithelium-derived factor (PEDF) protein can inhibit tumor growth and metastasis by anti-angiogenesis and pro-apoptosis. In this study, we prepared a PEDF-DNA-loaded liposome for cancer-targeted gene therapy for metastatic CRC using an iRGD peptide. Our results showed that cancer-targeted PEDF-DNA liposomes (R-LP/PEDF) exhibited enhanced inhibitory effects on invasion, migration, and pro-apoptosis of CRC cells in vitro. In addition, it reduced metastasis tumor nodules in lung and prolonged the survival time in a mouse model of metastatic CRC.


Assuntos
Peptídeos Penetradores de Células/metabolismo , Neoplasias Colorretais/terapia , Proteínas do Olho/genética , Marcação de Genes , Neoplasias Pulmonares/prevenção & controle , Fatores de Crescimento Neural/genética , Oligopeptídeos/metabolismo , Serpinas/genética , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Peptídeos Penetradores de Células/química , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Proteínas do Olho/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fatores de Crescimento Neural/metabolismo , Oligopeptídeos/química , Receptores Imunológicos/metabolismo , Receptores de Peptídeos/metabolismo , Serpinas/metabolismo , Carga Tumoral
17.
J Leukoc Biol ; 107(1): 57-67, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31385383

RESUMO

Most information about the immune status of NK cells during sepsis has been obtained from animal models, athough data from clinical septic patients is limited. In this study, we aimed to decipher NK cell immunity of septic patients in a more comprehensive way. We found that cytotoxicity of NK cells dramatically decreased during sepsis, likely due to the reduction of cluster of differentiation (CD)3- CD56+ NK cells and a shift of phenotypic changes of NK group 2 member (NKG2) receptors, natural cytotoxicity receptors (NCRs) and killer immunoglobulin-like receptors (KIRs) toward inhibitory receptors demonstrated by CD3- CD56+ NK cells in septic patients. Expression of the activation indicator CD69 and cytotoxic associated marker CD107a on CD3- CD56+ NK cells in healthy adults was significantly lower than that of septic patients. Although perforin and granzyme B on CD3- CD56+ NK cells from all groups exhibited equivalently high levels, CD3- CD56+ NK cells from septic patients exhibited a much lower fold increase of CD69 and CD107a compared with healthy adults after coculturing with K562 cells in vitro. Cytokine production of IFN-γ and TNF-α on CD3- CD56+ NK cells in septic patients was also impaired after stimulation by PMA and ionomycin. We found that the proportion of NK cells in lymphocytes was negatively associated with patient 28 d death in septic patients. Phenotypic changes of a shift toward inhibitory receptors and impairment of effector functions of NK cells might be an important mechanism of immunosuppression during sepsis.


Assuntos
Complexo CD3/metabolismo , Antígeno CD56/metabolismo , Imunossupressão , Células Matadoras Naturais/imunologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/metabolismo , Receptor 1 Desencadeador da Citotoxicidade Natural/metabolismo , Receptores KIR/metabolismo , Sepse/imunologia , Adulto , Idoso , Estudos de Casos e Controles , Citocinas/metabolismo , Citotoxicidade Imunológica/imunologia , Feminino , Humanos , Células K562 , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/patologia , Masculino , Pessoa de Meia-Idade , Sepse/metabolismo , Sepse/patologia
18.
Mol Pharm ; 17(1): 229-238, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31765158

RESUMO

Eukaryotic translation initiation factors 3i (eIF3i) is a proto-oncogene that is overexpressed in various tumors, reducing its expression by eIF3i shRNA is a promising strategy to inhibit tumor growth or metastasis. Tumor cell is the target of eIF3i shRNA so that tumor-site accumulation could be important for fulfilling its therapeutic effect. Thus, the iRGD modified liposome (R-LP) was rationally synthesized to enhance the antitumor effect by active targeted delivery of eIF3i shRNA to B16F10 melanoma cells. R-LP encapsulating eIF3i shRNA gene (R-LP/sheIF3i) were prepared by a film dispersion method. The transfection experiment proves that R-LP could effectively transfect B16F10 cells. R-LP/sheIF3i notably restrained the migration, invasion, and adhesion of melanoma cells in vitro. In a mouse model of lung metastasis, R-LP/sheIF3i administered by intravenous injection suppressed pulmonary metastasis of melanoma by dramatically downregulated eIF3i expression and subsequently inhibiting tumor neovascularization and tumor cells proliferation in vivo. Our results provide a basis for tumor cells targeting strategies to reduce the expression of eIF3i by RNAi in the treatment of tumor metastasis.


Assuntos
Fator de Iniciação 3 em Eucariotos/genética , Terapia Genética , Neoplasias Pulmonares/secundário , Melanoma Experimental/secundário , Melanoma Experimental/terapia , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Fator de Iniciação 3 em Eucariotos/metabolismo , Lipossomos/química , Lipossomos/ultraestrutura , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Masculino , Melanoma Experimental/genética , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Neovascularização Patológica/genética , Oligopeptídeos/farmacologia , Oligopeptídeos/uso terapêutico , RNA Interferente Pequeno , Transfecção , Transplante Homólogo
19.
Crit Care ; 23(1): 267, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370866

RESUMO

BACKGROUND: Data that indicate vitamin A status in critically ill children with sepsis are sparse. The association between serum vitamin A levels and the clinical outcomes of sepsis has not been well assessed. The aim of this study was to assess the prevalence of vitamin A deficiency in critically ill children with sepsis and its association with clinical outcomes. METHODS: Critically ill children with sepsis admitted to the pediatric intensive care unit were engaged in this prospective study. Sex- and age-matched approximate-health children from the Department of Pediatric Surgery were enrolled as the control group. Blood samples were collected from all patients in the first 24 h of admission for the measurement of serum vitamin A status. We compared vitamin A status between the sepsis group and the control group. In addition, we compared the clinical characteristics of the two subgroups of septic patients with vitamin A deficiency and those without vitamin A deficiency. Univariate and multivariable methods were used to evaluate the association between vitamin A deficiency and septic shock. RESULTS: One hundred sixty septic children and 49 approximate-health children were enrolled in this study. Vitamin A deficiency was found in 94 (58.8%) subjects in the study group and 6 (12.2%) subjects in the control group (P < 0.001). In septic patients, 28-day mortality and hospital mortality in patients with vitamin A deficiency were not significantly higher than that in patients without vitamin A deficiency (P > 0.05). However, vitamin A levels were inversely associated with higher PRISM scores in septic children with VAD (r = - 0.260, P = 0.012). Vitamin A deficiency was associated with septic shock with an unadjusted odds ratio (OR) of 3.297 (95% confidence interval (CI), 1.169 to 9.300; P = 0.024). In a logistic model, vitamin A deficiency (OR, 4.630; 95% CI, 1.027-20.866; P = 0.046), procalcitonin (OR, 1.029; 95% CI, 1.009-1.048; P = 0.003), and the Pediatric Risk of Mortality scores (OR, 1.132; 95% CI, 1.009-1.228; P = 0.003) were independently associated with septic shock. CONCLUSION: The prevalence of vitamin A deficiency was high in children with sepsis. Vitamin A deficiency may be a marker of mortality in critically ill children with sepsis. TRIAL REGISTRATION: Clinicaltrials.gov , NCT03598127.


Assuntos
Sepse/complicações , Deficiência de Vitamina A/fisiopatologia , Vitamina A/análise , Adolescente , Biomarcadores/análise , Biomarcadores/sangue , Criança , Pré-Escolar , China/epidemiologia , Estado Terminal/epidemiologia , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Sepse/sangue , Sepse/fisiopatologia , Vitamina A/sangue
20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(2): 145-151, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-31106530

RESUMO

OBJECTIVE: To test the killing effect of type Ⅰ receptor tyrosine kinase-like orphan receptor (ROR1) chimeric antigen receptor T cell (CAR-T) on several ROR1-expressing tumor cells in vitro. METHODS: The CAR gene was designed and synthesized by constructing the lentiviral vector plasmid, and BamHⅠ/EcoRⅠ was used to identify the plasmid. The expression levels of ROR1 among a variety of tumor cell lines were compared using flow cytometry (FCM). The killing effect of CAR-T on positive cells was detected by FCM, the LDH assay and ELISA. RESULTS: The double enzyme digestion identified CAR gene was successfully constructed to the lentivirus vector plasmid. FCM detection showed that the efficiency of CAR-T infection was about 47.23%. Multiple tumor cells expressed ROR1 in varying degrees. The FCM and the LDH assay indicated that CAR-T specifically killed ROR1-positive tumor cells. On positive target cells, more interferonI-γ (FN-γ) could be released during the CAR-T killing process than control T (P<0.05). CONCLUSION: We successfully constructed ROR1 CAR-T. CAR-T can specifically kill ROR1-positive tumor cells and cause the release of large amounts of IFN-γ, providing an experimental basis for clinical application.


Assuntos
Imunoterapia Adotiva , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/imunologia , Receptores de Antígenos de Linfócitos T , Receptores de Antígenos Quiméricos , Linfócitos T/citologia , Linhagem Celular Tumoral , Humanos , Lentivirus
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA