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1.
Ann Oncol ; 31(4): 517-524, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32151507

RESUMO

BACKGROUND: Adenosquamous carcinoma (ASC) of the lung is a heterogeneous disease that is composed of both adenocarcinoma components (ACC) and squamous cell carcinoma components (SCCC). Their genomic profile, genetic origin, and clinical management remain controversial. PATIENTS AND METHODS: Resected ASC and metastatic tumor in regional lymph nodes (LNs) were collected. The ACC and SCCC were separated by microdissection of primary tumor. The 1021 cancer-related genes were evaluated by next-generation sequencing independently in ACC and SCCC and LNs. Shared and private alterations in the two components were investigated. In addition, genomic profiles of independent cohorts of adenocarcinomas and squamous cell carcinomas were examined for comparison. We have also carried out a retrospective study of ASCs with known EGFR mutation status from 11 hospitals in China for their clinical outcomes. RESULTS: The most frequent alterations in 28 surgically resected ASCs include EGFR (79%), TP53 (68%), MAP3K1 (14%) mutations, EGFR amplifications (32%), and MDM2 amplifications (18%). Twenty-seven patients (96%) had shared variations between ACC and SCCC, and pure SCCC metastases were not found in metastatic LNs among these patients. Only one patient with geographically separated ACC and SCCC had no shared mutations. Inter-component heterogeneity was a common genetic event of ACC and SCCC. The genomic profile of ASC was similar to that of 170 adenocarcinomas, but different from that of 62 squamous cell carcinomas. The incidence of EGFR mutations in the retrospective analysis of 517 ASCs was 51.8%. Among the 129 EGFR-positive patients who received EGFR-TKIs, the objective response rate was 56.6% and the median progression-free survival was 10.1 months (95% confidence interval: 9.0-11.2). CONCLUSIONS: The ACC and SCCC share a monoclonal origin, a majority with genetically inter-component heterogeneity. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR TKI.

2.
Eur Rev Med Pharmacol Sci ; 24(3): 1000-1006, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32096206

RESUMO

OBJECTIVE: To study the effect of strontium ranelate (SR) on steroid-induced osteonecrosis of the femoral head (SIONFH) in rabbits and its regulatory mechanism. MATERIALS AND METHODS: The ONFH model was established in 30 rabbits using steroid and they were randomly divided into Control group, Model group, and SR group. After SR intervention, the rabbits were sacrificed and sampled. The pathological injury of the femoral head in each group was detected via hematoxylin-eosin (HE) staining, the level of vascular endothelial growth factor (VEGF) in the femoral head in each group was detected via enzyme-linked immunosorbent assay (ELISA). The messenger ribonucleic acid (mRNA) and protein expression levels of transforming growth factor-ß1 (TGF-ß1), as well as the bone morphogenetic protein 2 (BMP2) in the femoral head in each group, were determined using Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting. RESULTS: The rabbit model of SIONFH was successfully established. Compared with Control group, the Model group had a severer pathological injury of the femoral head, a lower level of VEGF in the femoral head, significantly decreased mRNA and protein levels of TGF-ß1 and BMP2. Compared with Model group, the SR group had markedly improved pathological injury of the femoral head, a higher level of VEGF in the femoral head, significantly increased mRNA and protein levels of TGF-ß1, as well as BMP2. CONCLUSIONS: SR can remarkably improve the pathological injury of the femoral head and increase the expression of VEGF in SIONFH rabbits, whose potential mechanism may be related to the activation of the TGF-ß1/BMP2 signaling pathway.

3.
Am J Emerg Med ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-32001056

RESUMO

BACKGROUND: Current post-resuscitation guidelines recommend oxygen titration in adults with the return of spontaneous circulation after cardiac arrest. However, the optimal peripheral oxygen saturation (SpO2) is still unclear for post-cardiac arrest care. METHODS: We conducted a retrospective observational study of prospectively collected data of all cardiac arrest patients admitted to the intensive care units between 2014 and 2015. The main exposure was SpO2, which were interfaced from bedside vital signs monitors as 1-min averages, and archived as 5-min median values. The proportion of time spent in different SpO2 categories was included in separate multivariable regression models along with covariates. The primary outcome measure was hospital mortality and the proportion of discharged home as the secondary outcome was reported. RESULTS: 2836 post-cardiac arrest patients in ICUs of 156 hospitals were included. 1235 (44%) patients died during hospitalization and 818 (29%) patients discharged home. With multivariate regression analysis, the proportion of time spent in SpO2 of ≤89%, 90%, 91%, and 92% were associated with higher hospital mortality. The proportion of time spent in SpO2 of 95%, 96%, and 97% were associated with a higher proportion of discharged home outcome, but not associated with hospital mortality. CONCLUSIONS: In this retrospective observational study, the optimal SpO2 for patients admitted to the intensive care unit after cardiac arrest may be 95-97%. Further investigation is warranted to determine if targeting SpO2 of 95-97% would improve patient-centered outcomes after cardiac arrest.

4.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(12): 1236-1241, 2019 Dec 06.
Artigo em Chinês | MEDLINE | ID: mdl-31795579

RESUMO

Objective: To investigate the content of persistent organic pollutants (POPs) in fish from Dongting Lake. Methods: Ten sample collection points were set in lakeside city Yueyang and Yuanjiang. In July (wet season) and November (dry season) of 2012, 13 common fish species were captured by convenience sampling in Dongting Lake. Two to three fish with similar weight were selected in each season for the same species of fish. After sample preparation and pretreatment, the contents of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls (dl-PCBs), indicator polychlorinated biphenyls and polybrominated diphenyls ether (PBDEs) in the samples were determined by high resolution gas chromatographer-high resolution mass spectrometry. Toxicity Equivalents (TEQ) of PCDD/Fs and dl-PCBs were calculated according to the revised toxicity equivalent factor (TEF) of WHO in 2005. The contents of POPs were expressed by median and quavtile. The differences of POPs in fish in different periods were compared by Wilcoxon rank sum test. Results: The content of PCDD/Fs of fish in Dongting Lake in wet season was 12.397 (8.865, 24.964) pg/g, higher than that in the dry season 0.771 (0.490, 1.442) pg/g (P<0.001), and the toxicity equivalent quantity (TEQ) were 0.150 (0.066,0.528) and 0.143 (0.066, 0.235) pg-TEQ/g without statistically significant difference (P>0.05). For the fish in wet and dry season from Dongting Lake,Σdl-PCBs of fish were 66.475 (28.065, 77.794) and 24.205 (18.237, 90.777) pg/g, respectively, and the TEQ were 0.061 (0.046, 0.268) and 0.075 (0.054, 0.182) pg-TEQ/g; Σ indicative PCBs were 237.764 (153.896, 335.483) and 119.711 (52.171, 408.696) pg/g, respectively; Σ PBDEs were 106.513 (64.834, 164.860) and 86.837 (61.872, 177.108) pg/g, respectively. The highest content of PCDD/Fs was found in grass carp (198.360 pg/g) in wet season. The higher content of PCBs was found in long-necked fish (2 332.509 pg/g) and PBDEs was found in pelteobagrus fulvidraco (343.857 pg/g), respectively. Conclusion: A lower burden was found in fishes from Dongting Lake, and the content of POPs varied in different seasons and fishes.


Assuntos
Poluentes Ambientais , Peixes/metabolismo , Lagos/análise , Espectrometria de Massas/métodos , Dibenzodioxinas Policloradas/análise , Poluentes Químicos da Água/análise , Animais , Benzofuranos , China , Dibenzofuranos , Dibenzofuranos Policlorados , Lagos/química , Bifenilos Policlorados , Dibenzodioxinas Policloradas/efeitos adversos , Dibenzodioxinas Policloradas/metabolismo , Poluentes Químicos da Água/metabolismo
5.
Zhonghua Yi Xue Za Zhi ; 99(38): 3014-3018, 2019 Oct 15.
Artigo em Chinês | MEDLINE | ID: mdl-31607035

RESUMO

Objective: To observe the effect of KLF3 on the expression of STAT3 in breast cancer cells, and to explore the potential mechanism of KLF3 affecting the movement, migration and invasion of breast cancer cells. Methods: Firstly, the expression of STAT3 was detected by Western blot, real-time fluorescent quantitative PCR, luciferase reporter system and chromatin immunoprecipitation in breast cancer cells. Secondly, the STAT3 promoter mutant was constructed. The plasmid further confirmed the effect of KLF3 on the activity of STAT3 promoter; the cell scratching test and Transwell method were used to detect the ability of cell movement, migration and invasion. Finally, animal experiments were conducted to verify the effect of knockdown of KLF3 on tumor metastasis in animals. Results: In breast cancer cells, knockdown of KLF3 promoted STAT3 protein expression. The mRNA level of STAT3 was increased by (3.58±0.65) fold after knockdown of KLF3 in MDA-MB-231 cells, while the mRNA level of STAT3 was increased by (2.28±0.19) fold after KLF3 knockdown in MCF-7 cells (P<0.001). KLF3 boundto the promoter region of STAT3. The transcriptional activity of STAT3 increased by (2.47±0.87) fold after knockdown of KLF3 in MDA-MB-231 cells, while the transcriptional activity of STAT3 increased by (2.63±0.65) fold after KLF3 knockdown in MCF-7 cells, P<0.01. KLF3 knockdown inhibitedthe movement,migrate and invade of breast cancer cells. Based on this, silence STAT3 partially reversed the function of KLF3. Knockdown of KLF3 promotedtumor metastasis in mice. Conclusions: KLF3 knockdown can promote the transcriptional activity of STAT3, which promotes the protein expression of the latter. KLF3 can affect the movement, migration and invasion of breast cancer cells through STAT3. KLF3 may be a potential target for the treatment of metastatic breast cancer.


Assuntos
Neoplasias da Mama , Animais , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores de Transcrição Kruppel-Like , Células MCF-7 , Camundongos , Invasividade Neoplásica , Fator de Transcrição STAT3
6.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(8): 729-735, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31422610

RESUMO

Objective: To explore the feasibility of assessing complications registration through medical information. Methods: A descriptive case series study was performed to retrospectively collect medical information and complication registration information of gastric cancer patients at Department of Gastrointestinal Cancer Center Ward I, Peking University Cancer Hospital from November 1, 2016 to March 1, 2017 (the first period), and from November 1, 2018 to March 1, 2019 (the second period). Case inclusion criteria: (1) adenocarcinoma confirmed by gastroscopy and biopsy; (2) patients undergoing open surgery or laparoscopic radical gastrectomy; (3) complete postoperative medical information and complication information. Patients who were directly transferred to ICU after surgery and underwent emergency surgery were excluded. Because difference of the complication registration procedure at our department existed before and after 2018, so the above two periods were selected to be used for analysis on enrolled patients. The prescription information during hospitalization, including nursing, medication, laboratory examination, transference, surgical advice, etc. were compared with the current Standard Operating Procedure (SOP, including preoperative routine examinations, inspection, perioperative preventive antibiotic use, postoperative observational tests, inspection, routine nutritional support, prophylactic anticoagulation, and prophylactic inhibition of pancreatic enzymes, etc.) for gastric cancer at our department. Medical order beyond SOP was defined as medical order variation. Postoperative complication was diagnosed using the Clavien-Dindo classification criteria, which was divided into I, II, IIIa, IIIb, IVa, IVb, and V. Medical order variation and complication registration information were compared between the two periods, including consistence between medical order variation and complication registration, missing report, underestimation or overestimation of medical order variation, and registration rate of medical order variation [registration rate = (total number of patients-number of missing report patients)/total number of patients], severe complications (Clavien-Dindo classification ≥ III), medical order variation deviating from SOP and the corresponding inferred grading of complication. The data was organized using Microsoft Office Excel 2010. Results: A total of 177 gastric cancer patients were included in the analysis. The first period group and the second period group comprised 89 and 88 cases, respectively. The registrated complication rate was 23.6% (21/89) and 36.4% (32/88), and the incidence of severe complication was 2.2% (2/89) and 4.5% (4/88) in the first and the second period, respectively. The complication rate inferred from medical order variation was 74.2% (66/89) and 78.4% (69/88), and the incidence of severe complication was 7.9% (7/89) and 4.5% (4/88) in the first and second period, respectively. In the first and second period, the proportions of medical order variation in accordance with registered complication were 36.0% and 45.5% respectively; the proportion of underestimation, overestimation and missing report were 5.6% and 4.5%, 4.5% and 4.5%, 53.9% and 45.5%, respectively; the registration rate of medical order variation was 46.1% and 54.5%; the number of case with grade I complications inferred from medical order variation was 34 (38.2%) and 25 (28.4%), respectively; and the number of grade II was 12 (13.5%) and 15 cases (17.0%), respectively. The reason of the missing report of medical order variation corresponding to grade I complication was mainly the single use of analgesic drugs outside SOP, accounting for 76.5% (26/34) and 64.0% (16/25) in the first and second period respectively, and that corresponding to grade II complication was mainly the use of non-prophylactic antibiotics, accounting for 9/12 cases and 5/15 cases, respectively. Conclusions: Medical information can evaluate the morbidity of complication feasibly and effectively. Attention should be paid to routine registration to avoid specific missing report.


Assuntos
Adenocarcinoma/cirurgia , Gastrectomia/efeitos adversos , Registros Médicos/normas , Sistema de Registros/normas , Neoplasias Gástricas/cirurgia , Estudos de Viabilidade , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
7.
Artigo em Chinês | MEDLINE | ID: mdl-31256519

RESUMO

Objective: To explore the effect of the umbilical cord mesenchymal stem cells(UC-MSCs) on the pulmonary fibrosis in silicosis rats. Methods: SPF male Sprague Dawley rats were randomly divided into control group, silica model group and UC-MSCs treatment group with 12 rats each group. SiO(2) intra-tracheal injection(0.5 ml of 50 mg/ml/rat) were applied to silica model group and UC-MSCs treatment groups. After that UC-MSCs treatment group received 1 ml UC-MSCs suspension (3×10(6) cells/ml) by tail vein injection on the 29th, 36th, 43th and 50th day after exposure to the first silica suspension. On the 60th and 75th day after exposure to silica suspension, all animals were examed for pulmonary CT. Then the rats were euthanized on 75th day after the first exposure to silica.Lung's histopathological examination of the rats from all the groups were carried out. The content of hydroxyproline in lungs, TGF-ß1 and IL-6 in serum were examined. Results: The lung's histopathological examination showed no obvious inflammatory cell and no fibrosis in the lung tissue of the control group, there were a lot of inflammatory cell aggregation and collagen fiber deposition in silica model group, while in the UC-MSCs intervention group and treatment group, there were less inflammatory cells and collagen fiber. The rats from silica model groups had higher HYP, TGF-ß1 and IL-6 than the rats from UC-MSCs treatment group and control group. Lung fields of rats in the control group were clear and no obvious high-density shadow. Different-sized granular high-density shadows or reticular fibrous shadows were found diffusely distributed in the lungs of the rats in silica model group. Lung field of rats in UC-MSCs intervention group and treatment group were less high density shadows, and more clear. Conclusion: UC-MSCs can alleviate the pulmonary fibrosis in silica model rats through regulating the secretion of some fibrosis related cytokines.


Assuntos
Fibrose Pulmonar Idiopática , Células-Tronco Mesenquimais , Silicose , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Dióxido de Silício , Cordão Umbilical
8.
Ann Oncol ; 30(3): 431-438, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30689702

RESUMO

BACKGROUND: Occult peritoneal metastasis (PM) in advanced gastric cancer (AGC) patients is highly possible to be missed on computed tomography (CT) images. Patients with occult PMs are subject to late detection or even improper surgical treatment. We therefore aimed to develop a radiomic nomogram to preoperatively identify occult PMs in AGC patients. PATIENTS AND METHODS: A total of 554 AGC patients from 4 centers were divided into 1 training, 1 internal validation, and 2 external validation cohorts. All patients' PM status was firstly diagnosed as negative by CT, but later confirmed by laparoscopy (PM-positive n = 122, PM-negative n = 432). Radiomic signatures reflecting phenotypes of the primary tumor (RS1) and peritoneum region (RS2) were built as predictors of PM from 266 quantitative image features. Individualized nomograms of PM status incorporating RS1, RS2, or clinical factors were developed and evaluated regarding prediction ability. RESULTS: RS1, RS2, and Lauren type were significant predictors of occult PM (all P < 0.05). A nomogram of these three factors demonstrated better diagnostic accuracy than the model with RS1, RS2, or clinical factors alone (all net reclassification improvement P < 0.05). The area under curve yielded was 0.958 [95% confidence interval (CI) 0.923-0.993], 0.941 (95% CI 0.904-0.977), 0.928 (95% CI 0.886-0.971), and 0.920 (95% CI 0.862-0.978) for the training, internal, and two external validation cohorts, respectively. Stratification analysis showed that this nomogram had potential generalization ability. CONCLUSION: CT phenotypes of both primary tumor and nearby peritoneum are significantly associated with occult PM status. A nomogram of these CT phenotypes and Lauren type has an excellent prediction ability of occult PM, and may have significant clinical implications on early detection of occult PM for AGC.

9.
Zhonghua Zhong Liu Za Zhi ; 40(10): 736-743, 2018 Oct 23.
Artigo em Chinês | MEDLINE | ID: mdl-30392337

RESUMO

Objective: To estimate the incidence and mortality of laryngeal cancer in China based on the cancer registration data in 2014, collected by the National Central Cancer Registry (NCCR), and to provide support data for the control and prevention of laryngeal cancer. Methods: The incident and death data of laryngeal cancer in 2014 from 339 cancer registries met the quality criteria of NCCR, and then adopted for analysis. The incident and death number, crude rate, age standardized rate, truncated rate and proportion which stratified by areas (urban/rural) and age were calculated. The nationwide incidence and mortality of laryngeal cancer in 2014 were estimated by combining with those data on national population in 2014. Chinese population census in 2000 and Segi's population were used for age-standardized incidence/mortality rates. Results: It was estimates that 23.4 thousand new cases of laryngeal cancer occurred in China in 2014. There were 20.8 thousand males and 2.6 thousand females. And 14.5 thousand occurred in urban areas, while 8.9 thousand in rural areas. The age standardized rates of incidence by world standard population (ASRs world) in male, female and both genders were 2.05/100, 000, 0.24/100, 000 and 1.14/100, 000, respectively, whereas those were 1.22/100, 000 and 1.03/100, 000 for urban and rural areas. The incidence was much higher in males than females, and slightly higher in urban areas than those in rural areas. Moreover, it was estimates that 13.2 thousand death cases of laryngeal cancer occurred in China in 2014. There were 11.5 thousand males and 1.7 thousand females. And 7.8 thousand occurred in urban areas, while 5.4 thousand in rural areas. The age standardized rates of mortality by ASRs world in male, female and both genders were 1.08/100, 000, 0.14/100, 000 and 0.60/100, 000, respectively, whereas those were 0.60/100, 000 and 0.59/100, 000 for urban and rural areas. The mortality was much higher in males than females, and slightly higher in urban areas than those in rural areas. In males, the age specific incidence and mortality of laryngeal cancer increased greatly from 40-44 and 45-44 years old, respectively, and peaked at age group of 75-79 and >85 years old. In females, the age specific incidence and mortality increased slowly from 50-54 and 60-64 years old, respectively, and peaked at age group of 80-84 and >85 years old. The trends remained similar in urban and rural areas, except for the different peak ages. Conclusions: The incidence and mortality of laryngeal cancer in China are at middle-low levels worldwide, and there are obvious differences between urban and rural areas with distinct gender disparity. Comprehensive prevention and control strategies should be carried out according to local status and age groups.


Assuntos
Neoplasias Laríngeas/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Incidência , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/prevenção & controle , Masculino , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , População Rural/estatística & dados numéricos , Distribuição por Sexo , População Urbana/estatística & dados numéricos
10.
Zhonghua Liu Xing Bing Xue Za Zhi ; 39(6): 810-815, 2018 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-29936752

RESUMO

Objective: To explore the effect of BMI and waist circumference on diabetes of adults. Methods: After excluding participants with heart disease, stroke, cancer and diabetes at baseline study, 53 916 people aged 30-79 in the China Kadoorie Biobank (CKB) study from Tongxiang city of Zhejiang province were recruited. Cox regression model was used to estimate the hazards ratios (HR) for the associations of baseline BMI and waist circumference with incident diabetes. Results: Among 391 512 person-years of the follow-up program between 2004 and 2013 (median 7.26 years), a total of 944 men and 1 643 women were diagnosed as having diabetes. Compared to those with normal weight, after adjusting for known or potential factors, HR of both overweight and obesity in men for incident diabetes appeared as 2.72 (95%CI: 2.47-2.99) and 6.27 (95%CI: 5.33-7.36), respectively. The corresponding figures in women were 2.19 (95%CI: 2.04-2.36) and 3.78 (95%CI: 3.36-4.26). Compared to those with normal waist circumference, after adjusting for known or potential factors, HR of Ⅰgrade andⅡgrade in men for diabetes were 2.56 (95%CI: 2.22-2.95) and 4.66 (95%CI: 4.14-5.24), respectively. The corresponding figures in women were 1.99 (95%CI: 1.80-2.21) and 3.16 (95%CI: 2.90-3.44), respectively. Conclusions: Overweight, obesity and central obesity were all associated with the increased incident of diabetes. Strategies on diabetes prevention should include not only losing weight, but reducing waist circumference as well.


Assuntos
Índice de Massa Corporal , Diabetes Mellitus/epidemiologia , Obesidade Abdominal/epidemiologia , Circunferência da Cintura , Adulto , Idoso , China/epidemiologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/etnologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
11.
Nanoscale Res Lett ; 13(1): 131, 2018 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-29704071

RESUMO

Atom probe tomography (APT) coupling high-resolution transmission electron microscopy (HRTEM) was used to analyze the fraction and compositions of different nanoparticles in two-stage double peaks aging process of Al-Zn-Mg alloy. Al content is found to be closely related to the size of nanoparticles and it can be greater than ~ 50.0 at. % in the nanoparticle with the equivalent radius under ~ 3.0 nm. Correspondingly, Al content of the nanoparticle, with the equivalent radius over ~ 5.0 nm, is measured under ~ 40.0 at. %. Evolution from Guinier-Preston (G.P.) zone to η phase is a growing process where Mg and Zn atoms enter the nanoparticle, therefore rejecting Al atoms. G.P. zones can take up a number fraction of ~ 85.0 and ~ 22.7% of nanoparticles in the first and second peak-aged samples, respectively, and even in the over-aged (T73) sample, they can still be found. As aging time increases, fraction of η' phases monotonically rises to the peak value (~ 54.5%) in the second peak-aged state and then drops, which is significant for the second hardness peak and directly proves their function as the transitional medium. In T73 state, ~ 63.3% nanoparticles compose of η phases, which were measured to still contain ~ 10.2 to ~ 36.4 at. % Al atoms.

12.
Leukemia ; 32(5): 1147-1156, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29434279

RESUMO

Aberrant activation of the JAK3-STAT signaling pathway is a characteristic feature of many hematological malignancies. In particular, hyperactivity of this cascade has been observed in natural killer/T-cell lymphoma (NKTL) cases. Although the first-in-class JAK3 inhibitor tofacitinib blocks JAK3 activity in NKTL both in vitro and in vivo, its clinical utilization in cancer therapy has been limited by the pan-JAK inhibition activity. To improve the therapeutic efficacy of JAK3 inhibition in NKTL, we have developed a highly selective and durable JAK3 inhibitor PRN371 that potently inhibits JAK3 activity over the other JAK family members JAK1, JAK2, and TYK2. PRN371 effectively suppresses NKTL cell proliferation and induces apoptosis through abrogation of the JAK3-STAT signaling. Moreover, the activity of PRN371 has a more durable inhibition on JAK3 compared to tofacitinib in vitro, leading to significant tumor growth inhibition in a NKTL xenograft model harboring JAK3 activating mutation. These findings provide a novel therapeutic approach for the treatment of NKTL.


Assuntos
Janus Quinase 3/antagonistas & inibidores , Linfoma de Células T/tratamento farmacológico , Piridonas/uso terapêutico , Pirimidinas/uso terapêutico , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Xenoenxertos/efeitos dos fármacos , Humanos , Janus Quinase 3/metabolismo , Camundongos , Células T Matadoras Naturais/patologia , Piridonas/farmacologia , Pirimidinas/farmacologia
13.
Genet Mol Res ; 16(3)2017 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-28692119

RESUMO

Knee osteoarthritis (KOA) is a common degenerative joint disease and immune system dysregulation has been implicated in its pathogenesis. The effect of arthroscopic knee surgery, an important method for KOA diagnosis and treatment, on the expression of immune regulators remains poorly understood. We aimed to investigate the clinical efficacy of such surgery and its impact on IL-1ß, CXCL13, and TNF-α expression in the knee joint synovial fluid of osteoarthritis patients. Fifty-seven patients having undergone arthroscopic knee surgery in our hospital were included. Visual analog scale (VAS) and Lysholm scores were recorded before surgery, and knee joint synovial fluid was collected during the procedure. According to Outerbridge cartilage damage score (grade 0, 1, 2, 3, or 4), patients were divided into five groups. In addition, VAS and Lysholm scores were recorded and knee joint synovial fluid was collected after a six-month follow-up period. Expression of IL-1ß, CXCL13, and TNF-α in synovial fluid samples was then measured. In each group, levels of these molecules and VAS and Lysholm scores were significantly lower after surgery (P < 0.05). IL-1ß, CXCL13, and TNF-α levels were significantly elevated in patients with higher cartilage damage scores compared to those with lower scores. Arthroscopic knee surgery can reduce IL-1ß, CXCL13, and TNF-α levels in the knee joint synovial fluid of osteoarthritis patients. Moreover, reduced presence of these molecules correlates with clinical improvement of this condition. Therefore, reduction in IL-1ß, CXCL13, and TNF-α expression might be used as a factor for long-term osteoarthritis prognosis.


Assuntos
Artroplastia do Joelho/efeitos adversos , Quimiocina CXCL13/metabolismo , Interleucina-1beta/metabolismo , Osteoartrite do Joelho/metabolismo , Complicações Pós-Operatórias/metabolismo , Líquido Sinovial/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/cirurgia , Complicações Pós-Operatórias/patologia
14.
Clin Radiol ; 72(6): 517.e1-517.e6, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28292511

RESUMO

AIM: To determine the efficacy of dual Y-shaped covered airway stents to treat thoracic stomach-right main bronchus fistulae. MATERIAL AND METHODS: Fifteen patients who developed thoracic stomach-right main bronchus fistula after oesophageal cancer resection and postoperative irradiation were retrospectively analysed. All fistulae were close to the right upper lobe bronchus. Two Y-shaped covered airway stents were designed for each patient. Under radiographic guidance, one stent was placed from the right main bronchus into the bifurcation of upper lobe and intermediate bronchus, the other was placed from the trachea into both main bronchi. RESULTS: All fistulae were closed immediately after stenting. All patients could eat a semi-solid diet. The symptom of coughing while lying down resolved in all patients, and no complications, such as airway bleeding or pneumothorax, occurred. The average survival time was 26.65 months (range 2-40 months, 11 patients were still alive at the study end). Two patients died of tumour recurrence. Another two patients died of pulmonary infections. In one of these patients, there was a long delay between symptom onset and stenting. In the other patient, a small rupture occurred in the silicone membrane covering the stent, which allowed the leakage of gastric contents into the lung. CONCLUSION: Dual Y-shaped covered airway stent placement is feasible and safe to treat thoracic stomach-right main bronchus fistulae. Improvements to the material covering the stents is required.


Assuntos
Fístula Brônquica/cirurgia , Fístula Gástrica/cirurgia , Stents , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Resultado do Tratamento
15.
Zhonghua Fu Chan Ke Za Zhi ; 51(9): 683-687, 2016 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-27671050

RESUMO

Objective: To study the clinical and pathological characteristics of HPV-negative cervical cancer patients. Methods: Retrospective analysis of 785 cervical cancer patients in Guangdong Women and Children Hospital from Jan. 2005 to Oct. 2015. By detecting high- risk HPV infection by flow-through hybridization genechip technique. Results: (1)Among 785 cases of cervical cancer, 71 cases were negative for HPV infection tested by genechip technique, accounting for 9.0%(71/785), and the relative light units/cut off(RLU/CO)ratios of these 71 cases were less than 1 by hybird capture Ⅱ(HC-Ⅱ)methods. The results showed that the positive coincident rate of genechip technique detecting result with HC-Ⅱ method was 100.0%(71/71).(2)There was no difference between 43(60.6%)cases from 41-55 years old of 71 cases of HPV-negative patients and 392(54.9%)cases from 41- 55 years old of 714 cases of HPV infection patients(χ2=15.63, P=0.571). Among 71 cases of HPV-negative patients, 32 cases of patients with doing TCT, 6(18.8%)cases for normal, 10(31.2%)cases for atypical squamous cells of undetermined significance(ASCUS), 3(9.4%)cases for atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion(ASC-H), 3(9.4%)cases for low-grade squamous intraepithelial lesions(LSIL), 8(25.0%)cases for hight-grade squamous intraepithelial lesions(HSIL), 2(6.2%)cases for squamous cell carcinoma(SCC). And there were 391 cases of patients with doing thin-prep cytologic test(TCT)of 714 HPV infection patients, 60(15.3%)cases for normal, 61(15.6%)cases for ASCUS, 28(7.2%)cases for ASC-H, 29(7.4%)cases for LSIL, 164(41.9%)cases for HSIL, 49(12.5%)cases for SCC. There was no difference of TCT between HPV infection and HPV-negative patients(P>0.05). Among 70 cases from 71 patients with negative for HPV infection, there were 8(11.4%)cases in stage Ⅰ a, 26(37.1%)cases in stage Ⅰ b1, 12(17.1%)cases in stage Ⅰb2, 11(15.7%)cases in stage Ⅱa, 10(14.3%)cases in stage Ⅱb, 3(4.3%)cases in stage Ⅲ-Ⅳ. There were 118(16.6%)cases in stage Ⅰa, 261(36.8%)cases in stage Ⅰb1, 72(10.1%)cases in stage Ⅰb2, 152(21.4%)cases in stage Ⅱa, 87(12.3%)cases in stage Ⅱb, 20(2.8%)cases in stage Ⅲ-Ⅳ in 710 cases of HPV infection patients, in which there were no difference of clinical stage between HPV infection and HPV-negative patients(P>0.05). Among 69 cases from 71 patients HPV-negative infection, there were 51(73.9%)cases for squamous carcinoma, 13(18.8%)cases for adenocarcinoma, 5(7.2%)cases for adenosquamous carcinoma; and 593(87.2%)cases for squamous carcinoma, 38(5.6%)cases for adenocarcinoma, 39(5.7%)cases for adenosquamous carcinoma, 10(1.5%)case for others were in 680 patients of HPV infection, in which there was significant difference of adenocarcinoma between HPV infection and HPV-negative patients(χ2=11.96, P=0.001). Conclusions: Flow-through hybridization genechip technique is the method of high sensitivity to detect high-risk type HPV, as like HC-Ⅱ method. HPV-negative of cervical cancer occurs mainly in 41- 55 years old. Adenocarcinoma incidence is significantly higher in HPV-negative cases than those patients with infection of HPV positive.


Assuntos
Neoplasias do Colo do Útero , Adulto , Carcinoma de Células Escamosas , Citodiagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae , Infecções por Papillomavirus , Estudos Retrospectivos , Fatores de Risco
16.
Artigo em Chinês | MEDLINE | ID: mdl-27682482

RESUMO

Objective: To screen sensitive indicators of renal injury in lead workers using benchmark dose method. Methods: Of the 486 subjects,116 did not occupationally contact to lead as a control. The blood lead was considered as exposure biomarker, while Uß2-MG and UNAG as effect biomarkers for renal injury. The BMD and BMDL of blood lead were estimated at the 10% benchmark response using BMDS Version 2.6. Results: There was statistical rise in blood lead between the lead group and control group (P<0.05) ; and the blood lead level was divided into four groups by quarterback spacing method, among which UNAG was statistically different (P<0.05) . There was an increased prevalence of abnormal rates of Uß2-MG and UNAG with increasing blood lead concentration (P<0.05) , after trend chi-square test. BMD and BMDL of UNAG and Uß2-MG were 602.784/431.838 µg/L and 130.398/100.981 µg/L caculated by Log-Probit model, respectively. Conclusions: Occupational lead exposure may cause kidney damage, and UNAG could be as a more sensitive marker for monitoring early renal injury than Uß2-MG.


Assuntos
Nefropatias/induzido quimicamente , Chumbo/toxicidade , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Adulto , Benchmarking , Biomarcadores/análise , Humanos , Rim , Chumbo/sangue , Prevalência , Microglobulina beta-2
17.
Zhonghua Zhong Liu Za Zhi ; 38(8): 628-31, 2016 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-27531485

RESUMO

OBJECTIVE: To investigate the advantages of thoracoabdominal radical gastrectomy for advanced Siewert type Ⅱ adenocarcinoma of the esophagogastric junction. METHODS: Clinical data of 86 patients with Siewert type Ⅱ adennocarcinoma of the esophagogastric junction who received surgical treatment at the Henan Provincial Tumor Hospital from January 2015 to January 2016 were retrospectively analyzed. Among them, 44 patients underwent abdominal operation (abdominal group), and 42 patients underwent thoracoabdominal radical gastrectomy (thoraco-abdominal group). The operation time, lymph node number, distance between the tumor and cutting edge, amount of intraoperational blood loss, postoperative pulmonary complications, and postoperative hospital stay in the two groups were compared. RESULTS: Comparing the thoracoabdominal group with the abdominal group, the number of removed lymph nodes was 41.57±9.22 vs. 35.09±10.61 (P<0.01), the number of removed mediastinal lymph nodes was 6.38±1.50 vs. 3.52±1.42 (P<0.01), the distance between the tumor and cut edge was (5.62±0.73) cm vs. (3.30±0.85) cm (P<0.01), whereas the operation time, intraoperative blood loss, postoperative pulmonary complications, occurrence of anastomotic leakage and hospital stay were statistically not significantly different (P>0.05 for all). CONCLUSIONS: For patients with advanced Siewert type Ⅱ adenocarcinoma of the esophagogastric junction, radical gastrectomy through thoracoabdominal approach can resect a longer segment of the esophagus, dissect more mediastinal lymph nodes, and does not increase post-operative complications and extend hospital stay, thus, exhibits obvious advantages in the surgical treatment of Siewert Ⅱ adenocarcinoma of the esophagogastric junction.


Assuntos
Adenocarcinoma , Junção Esofagogástrica , Neoplasias Gástricas , Perda Sanguínea Cirúrgica , Gastrectomia , Humanos , Excisão de Linfonodo , Linfonodos , Metástase Linfática , Estadiamento de Neoplasias , Duração da Cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos
18.
Artigo em Chinês | MEDLINE | ID: mdl-27220442

RESUMO

OBJECTIVE: The correlation of vitamin D receptor (VDR) gene polymorphism and blood lead level had been in doult, which allowed us to write this article. METHODS: Relevant studies about the blood lead and VDR B/b gene polymorphism which published from 1979-2015, were searched in multiple bibliographic databases, such as: CNKI, Wanfang Database, PUBMED. Of the ten references selceted, three were divided into two groups which were classified as different researches, so there were thirteen studies in the meta-analysis. According to the level of blood lead, the studies were analyzed by three groups: normal group, low dose grou and high dose group. The analysis was performed by stata 12.0 software. RESULTS: The blood lead level of VDR B/b genotype was significantly difference in all the three groups (P<0.05) , but there were apparent heterogeneity between normal group and low dose group (P<0.05, I(2)=84.2%; P<0.05, I(2)=88.9%) , except the high dose group (P>0.05, I(2)=12.7%) ; after adjusted, all showed no heterogeneity, and the results were still the same. CONCLUSION: The genotype of VDR may be correlated with blood lead, and the levels of blood lead varied with different genetypes.


Assuntos
Receptores de Calcitriol/genética , Genótipo , Humanos , Chumbo
19.
Leukemia ; 30(6): 1311-9, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26854024

RESUMO

Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.


Assuntos
Linfoma de Células T Associado a Enteropatia/metabolismo , Janus Quinases/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Adulto , Idoso , Idoso de 80 Anos ou mais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Linfoma de Células T Associado a Enteropatia/patologia , Feminino , Subunidade alfa Gi2 de Proteína de Ligação ao GTP/genética , Perfilação da Expressão Gênica , Humanos , Janus Quinase 3/genética , Masculino , Pessoa de Meia-Idade , Mutação , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT5/genética , Transdução de Sinais/efeitos dos fármacos , Adulto Jovem
20.
Colorectal Dis ; 18(3): 255-63, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26400111

RESUMO

AIM: The aim of this study was to develop a prognostic scoring system to predict the outcome of patients with unresectable metastatic colon cancer who received primary colon tumour resection. METHOD: Patients with confirmed metastatic colon cancer treated at the Peking University Cancer Hospital between 2003 and 2012 were reviewed retrospectively. The correlation of clinicopathological factors with overall survival was analysed using the Kaplan-Meier method and the log-rank test. Independent prognostic factors were identified using a Cox proportional hazards regression model and were then combined to form a prognostic scoring system. RESULTS: A total of 110 eligible patients were included in the study. The median survival time was 10.4 months and the 2-year overall survival (OS) rate was 21.8%. Age over 70 years, an alkaline phosphatase (ALP) level over 160 IU/l, ascites, a platelet/lymphocyte ratio (PLR) above 162 and no postoperative therapy were independently associated with a shorter OS in multivariate analysis. Age, ALP, ascites and PLR were subsequently combined to form the so-called AAAP scoring system. Patients were classified into high, medium and low risk groups according to the score obtained. There were significant differences in OS between each group (P < 0.001). CONCLUSION: Age, ALP, ascites, PLR and postoperative therapy were independent prognostic factors for survival of patients with metastatic colonic cancer who underwent primary tumour resection. The AAAP scoring system may be a useful tool for surgical decision making.


Assuntos
Biomarcadores Tumorais/sangue , Colectomia/mortalidade , Neoplasias do Colo/mortalidade , Neoplasias do Colo/cirurgia , Metástase Linfática/patologia , Fatores Etários , Idoso , Fosfatase Alcalina/análise , Ascite/patologia , Colo/patologia , Colo/cirurgia , Neoplasias do Colo/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neutrófilos , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
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