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1.
Artigo em Chinês | MEDLINE | ID: mdl-36229211

RESUMO

Objective: To investigate the occupational stress status of air traffic controllers (ATC) and analyze its influencing factors. Methods: By using cluster sampling method, 457 ATCs in an air traffic management bureau were selected as the investigation objects. The job content questionnaire (JCQ) and the effort reward imbalance questionnaire (ERI) were used to measure work requirements independent imbalance type and ERI type occupational stress separately and analyze the influencing factors. Results: Of the 457 ATCs, 81.84% (374/457) ATGs had work requirements independent imbalance type of occupational stress and 84.46% (386/457) ATGs had ERI type occupational stress. Univariate analysis showed that the factors of marital status, degree of education, age, length of service, title, job post, family monthly income, views on regular training, occurrence of emergency or unsafe events in last month and monthly night shift frequency had various degrees of influence on the different factor scores of JCQ and ERI (P<0.01) . Logistic regression analysis showed that the level of JCQ type occupational stress of ATCs with junior titles and probationers was higher than those of intermediate/senior titles (P=0.000, 0.000) ; The ERI type occupational stress of probationers and junior titles ATCs was lower than those with intermediate/senior titles (P=0.000) . The ERI and JCQ type occupational stress level of tower post ATCs was higher than that of other two job post ATCs (P=0.001, 0.000, 0.000, 0.000) . The ATCs considering regular training had more disadvantages than advantages showed lower ERI type occupational stress level than those considering more advantages than disadvantages (P=0.000) . The ERI type occupational stress level of ATCs who experienced emergency or unsafe events in last month was higher than those who didn't (P=0.007) . Conclusion: A large proportion of ATCs had occupational stress. Management should adjust its policies and pay were attention to occupational stress of ATLs.


Assuntos
Estresse Ocupacional , Estudos Transversais , Emprego , Humanos , Satisfação no Emprego , Estresse Ocupacional/epidemiologia , Recompensa , Estresse Psicológico/epidemiologia , Inquéritos e Questionários
2.
Osteoarthritis Cartilage ; 30(2): 260-269, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34800632

RESUMO

OBJECTIVE: To explore clinicians' attitudes and beliefs about physical activity and exercise therapy as treatment for individuals with knee and/or hip osteoarthritis (OA). METHOD: This was a scoping review, mapping available knowledge about the topic derived from qualitative research designs and methods. A comprehensive search of selected databases (MEDLINE, EMBASE; CINAHL; Web of Science) was conducted and data were analysed thematically. RESULTS: Twelve articles met inclusion criteria. Thematic analysis identified three interrelated main themes: 1) Understandings of OA and its trajectory and management; 2) Attitudes to activity and exercise as part of OA management; 3) Clinicians' perceived knowledge of and expertise in OA management. Findings highlight that many clinicians involved in knee/hip OA management, particularly general practitioners and physiotherapists, perceive OA to be a low priority 'wear-and-tear' disease with expected progression of symptoms, making joint replacement surgery eventually inevitable. Further, many clinicians appear to lack knowledge about and interest in physical activity and exercise therapy in the management of knee/hip OA, and seem to show uncertainty about the effectiveness and safety of physical activity and exercise therapy on joint health. CONCLUSION: Clinicians' attitudes and beliefs about physical activity and exercise therapy in OA seem to reflect an outdated narrative which describes OA as a wear-and-tear disease with inevitable disease progression to joint replacement surgery. Clinicians need to adopt a contemporary narrative, which accurately reflects current knowledge and evidence-based practice, thereby ensuring consistent utilisation of exercise therapy as first-line care as recommended in OA guidelines.


Assuntos
Atitude do Pessoal de Saúde , Cultura , Terapia por Exercício , Exercício Físico , Conhecimentos, Atitudes e Prática em Saúde , Osteoartrite do Quadril/terapia , Osteoartrite do Joelho/terapia , Humanos
3.
Artigo em Chinês | MEDLINE | ID: mdl-34074093

RESUMO

In this paper, the related research on occupational hazards of civil aviation employees at home and abroad is reviewed, and the effects of noise, radioactivity, harmful gas, bad posture, occupational stress, fatigue and many other factors on the health of civil aviation employees are summarized. This paper describes the characteristics of occupational hazard factors and their effects on the health of civil aviation employees in order to provide a basis for the management of civil aviation related units to control occupational hazard factors. The occupational health problems of civil aviation employees need to be paid attention to and managed.


Assuntos
Aviação , Doenças Profissionais , Saúde Ocupacional , Estresse Ocupacional , Fadiga , Humanos , Ruído , Doenças Profissionais/epidemiologia , Doenças Profissionais/prevenção & controle
4.
Artigo em Chinês | MEDLINE | ID: mdl-32892581

RESUMO

Objective: To explore the index system and weight of occupational stress risk assessment for civil aviation air traffic controllers (ATC) . Methods: In October 2018, a total of 489 ATC staff from an air traffic administration bureau were selected by cluster sampling. Through ATC questionnaire survey, the basic information, the influencing factors of occupational stress and the degree of occupational stress were understood. Based on the order relation analysis method (GL method) , the influencing factors of ATC occupational stress in civil aviation are evaluated. The fuzzy relation synthesis principle is applied to carry out multi-level fuzzy evaluation on the subordinate degree of occupational stress risk, and the ATC occupational stress risk evaluation system model is established. The weight of each index in the index system is determined, Establish a three-level comprehensive evaluation index system for ATC occupational stress risk, and quantify the occupational stress risk, Each Civil Aviation ATC occupational stress index corresponds to different degree of stress. Results: The influence degree of ATC occupational stress from heavy to light is: work factor, psychological factor, event factor, management factor, physiological factor, equipment factor and environmental factor (weight value is 0.2652, 0.2265, 0.1832, 0.1253, 0.1154, 0.045 5, 0.038 9 respectively) . Conclusion: GL method can be used to comprehensively and quantitatively evaluate the occupational stress risk of Civil Aviation ATC, which may be a feasible way to evaluate the occupational stress risk of Civil Aviation ATC.


Assuntos
Aviação , Estresse Ocupacional/epidemiologia , Humanos , Inquéritos e Questionários
5.
Br J Surg ; 107(1): 14-19, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31763684

RESUMO

A subset of patients with early gastric cancer demonstrate early recurrence and poor survival despite margin-negative resection. This study used an extremes-of-survivorship approach to identify an association between TP53 hotspot mutations co-occurring with loss of heterozygosity and unexpectedly poor survival in early gastric cancer. This distinct genomic profile may be a novel biomarker of poor survival in patients with completely resected early gastric cancer, and warrants large-scale validation. Promising, validation needed.


Assuntos
Mutação/genética , Neoplasias Gástricas/cirurgia , Proteína Supressora de Tumor p53/genética , Idoso , Biomarcadores Tumorais/genética , Feminino , Marcadores Genéticos/genética , Genômica , Humanos , Perda de Heterozigosidade/genética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Sequenciamento Completo do Genoma
6.
Zhonghua Jie He He Hu Xi Za Zhi ; 41(5): 333-339, 2018 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-29747275

RESUMO

Objective: To investigate the molecular mechanism of contractility dysfunction of human bronchial smooth muscle cells induced by nicotine. Methods: Primary human bronchial smooth muscle cells were cultured in vitro. The cells were divided into a control group and a nicotine group which was treated with 10(-5) mol/L nicotine for 48 h and transfected with or without α7nAChR-siRNA (The siNC group, siNC + nicotine group and siα7nAChR + nicotine group). The effects of nicotine on the cell contractile function were examined by collagen gel shrinkage assay. The expressions of α7nAChR and TRPC6 protein in nicotine-treated human bronchial smooth muscle cells were detected by Western blotting. The change of intracellular calcium concentration by nicotine was detected by calcium ion imaging system.Data were analyzed by t test or single factor analysis of variance. Results: The area of collagen gel in the nicotine group (24±8)% was significantly lower than that in the control group (59±14)% (t=3.78, P<0.05). Compared with the control group, the expression of α7nAChR protein in nicotine-induced group (173±16)% was significantly higher than that of controls 100±0)%, t=-6.848, P<0.05. Compared with the siNC group [(72±10)%, (0.79±0.07), (0.41±0.04) and (0.17±0.02) respectively], the collagen gel area of siNC + nicotine group was significantly reduced by (37±10)%. However, the basal calcium level (1.04±0.02), store operated calcium entry level (SOCE, 0.68±0.03) and receptor operated calcium entry level (ROCE, 0.36±0.02) were remarkably elevated in the nicotine treated group (all P<0.05). Furthermore, compared with siNC + nicotine group, the area of collagen gel in siα7nAChR + nicotine group was significantly increased (62±10)%, and the basal calcium level (0.78±0.06), SOCE level (0.39±0.05) and ROCE level (0.15±0.02) were significantly reduced (all P<0.05). Conclusions: Nicotine can increase the expression of TRPC6 protein, SOCE and ROCE level, and increase the intracellular calcium concentration by upregulating the expression of α7nAChR protein, thereby promoting smooth muscle cell contraction.


Assuntos
Miócitos de Músculo Liso/efeitos dos fármacos , Nicotina/farmacologia , Cálcio/sangue , Canais de Cálcio , Células Cultivadas , Humanos , Músculo Liso
7.
Zhonghua Bing Li Xue Za Zhi ; 47(4): 263-268, 2018 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-29690665

RESUMO

Objective: To investigate the clinical and pathological features of spindle cell lipoma (SCL) and pleomorphic lipoma (PL) with emphasis on differential diagnosis. Methods: Sixty-five cases of SCL/PL from the archive of Department of Pathology, Fudan University Shanghai Cancer Center, from August of 2006 to June of 2017, were included in the study. Immunohistochemistry by EnVision method, MDM2 gene amplifycation and DDIT3 gene translocation by fluorescence in situ hybridization(FISH) were detected and the literature was reviewed. Results: There were 53 males and 12 females with age ranging from 26 to 82 years (mean, 57 years; median, 59 years). The majority of the lesions occurred in the neck/posterior neck/nuchal region, upper back and shoulder. A small percentage of lesions developed in the extremities, face and trunk, and rarely in the epiglottis, mediastinum, labium majus and perineum. Clinically, the tumor usually manifested as a slowly growing mass or nodule. It was often encapsulated, ranging from 1 to 13 cm (mean, 4.1 cm; median, 3.5 cm) in size. Microscopically, SCL was composed of mature adipose tissue, bland spindle cells and bright eosinophilic "ropey" collagen fibers that varied in proportion. Of 45 SCL, 28 cases (62.2%) were classical, 6 cases (13.3%) were myxoid, 5 cases (11.1%) were fat-poor, 3 cases (6.7%) were fat-free, and 3 cases (6.5%) were pseudoangiomatoid. PL showed similar features as SCL, but was characterized by the presence of scattered floret giant cells. Of 20 PL, 11 cases (55.0%) were classical, 6 cases (30.0%) were mixed SCL/PL, 3 cases (15.0%) were fat-free. Both SCL and PL contained scattered mast cells in the stroma. By immunohistochemistry, the spindle cells in SCL and the floret giant cells in PL showed strong positivity for CD34 (52/52, 100.0%), bcl-2 (24/26, 92.3%) and CD99 (6/6), whereas they were negative for S-100 protein and STAT6. FISH analysis of MDM2 (17 cases) and DDIT3 (4 cases) was negative in all cases. Follow-up information was available in 32 patients (3 to 96 months), with local recurrence in only one patient. Conclusions: SCL and PL belong to the same entity but may exhibit morphological disparities. Of note, the fat-poor and fat-free variants are easily mistaken for other mesenchymal tumors. Attention should be paid in their differential diagnosis.


Assuntos
Lipoma/patologia , Antígeno 12E7/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/metabolismo , China , Diagnóstico Diferencial , Feminino , Células Gigantes/patologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Lipoma/genética , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas S100/metabolismo , Fator de Transcrição STAT6/metabolismo , Fator de Transcrição CHOP/genética
8.
Zhonghua Bing Li Xue Za Zhi ; 46(6): 443-446, 2017 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-28592003
9.
Zhonghua Liu Xing Bing Xue Za Zhi ; 37(12): 1644-1646, 2016 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-27998414

RESUMO

Objective: To delineate the application of whole genome sequencing technology in the epidemiology of tuberculosis. Methods: From 2009 to 2012, nine Mycobacterium tuberculosis that sharing identical variable number of tandem repeats genotype (VNTR) patterns were reported from two TB cases designated hospitals. Both whole-genome sequencing analysis (WGS) and epidemiologic investigations were performed to describe the transmission patterns of these Mycobacterium tuberculosis. Results: By WGS analysis, two genomic clusters including 7 and 2 Mycobacterium tuberculosis were noticed, respectively. The cluster of 2 cases possessed more than 15 single nucleotide polymorphisms (SNPs) when compared to the cluster of 7 cases and suggesting that the transmission route was independent. The transmission chain based on the SNPs difference showed the process of the propagation direction and the accumulation of drug resistance mutations in each cluster. Conclusion: Using a WGS-based genomic epidemiologic approach, we were able to reconstruct the tuberculosis transmission network, tracing the putative source of the transmission and determining the transmission direction or the missing links.


Assuntos
Genoma Bacteriano , Mycobacterium tuberculosis , Tuberculose , Genômica , Genótipo , Humanos , Repetições Minissatélites , Epidemiologia Molecular , Polimorfismo de Nucleotídeo Único
10.
Zhonghua Jie He He Hu Xi Za Zhi ; 39(12): 944-947, 2016 Dec 12.
Artigo em Chinês | MEDLINE | ID: mdl-27938545

RESUMO

Objective: To investigate the prevalence of latent tuberculosis infection(LTBI) and associated risk factors among the tuberculosis(TB) contacts in Minhang District of Shanghai. Methods: A self-designed questionnaire was used to acquire socio-demographic information and to assess the degree of exposure to index cases. LTBI screening was performed by T-SPOT.TB assay. Pearson chi-square test and Logistic regression analyses were used to identify the risk factors associated with LTBI among the TB contacts. Results: A total of 137 contacts from 59 mycobacterial (culture) positive pulmonary TB patients were enrolled in this study. In these contacts, there were 54 men and 83 women, with the average age of 42. LTBI was identified in 20% (27/137) of these contacts. Several risk factors were found by logistic analyses in this study. The worse the ventilation in the exposure location was, the more likely to develop LTBI. Contacts aged more than 60 (42.1%) were 3.9 times more likely to develop LTBI than those aged less than 60 (16.1%). Individuals in contact with TB patients for more than 40 h/week(25.8%) had a 4.2 times risk of LTBI as compared to those for less than 40 h/week(6.8%). Conclusion: The prevalence of LTBI was 20% among the TB contacts in this study, highlighting the need of TB screening and intervention among TB contacts.


Assuntos
Busca de Comunicante , Tuberculose Latente/epidemiologia , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/etiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Vigilância em Saúde Pública , Fatores de Risco , Inquéritos e Questionários , Tuberculose , Tuberculose Pulmonar
11.
Waste Manag ; 58: 309-315, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27267794

RESUMO

Incineration fly ash, a waste from municipal solid waste incineration plant can be used to replace conventional filler as reinforcing filler to enhance the mechanical strength of a composite. Surface modification was performed on the incineration fly ash before mixing into the soft polymer matrix so as to improve interfacial bond of the filler and epoxy resin. In this study, detailed characterisation of mechanical, morphological and leaching behaviours of municipal solid waste incineration (MSWI) fly ash infused composite has been carried out. Flexural and tensile test was conducted to determine the effect on mechanical properties of the composite by varying the concentration of incineration fly ash filler added into polymer matrix and surface modification of incineration fly ash filler using silane coupling agent and colloidal mesoporous silica (CMS). The results indicated that composite infused with incineration fly ash filler surface treated with CMS shown improvement on the tensile and flexural strengths. In addition, SEM images showed that surface modification of incineration fly ash with colloidal mesoporous silica enhanced the interfacial bonding with polymer resin which explained the improvement of mechanical strength. Leaching test showed result of toxic metals such as Pb, Zn, Fe, Cu, Cr, Cd and Rb immobilised in the polymer matrix of the composite. Hence, the use of MSWI fly ash as reinforcing filler in the composite appears green and sustainable because this approach is a promising opportunity to substitute valuable raw material with MSWI fly ash.


Assuntos
Cinza de Carvão/química , Resinas Epóxi/química , Eliminação de Resíduos/métodos , Coloides/química , Incineração , Metais/química , Microscopia Eletrônica de Varredura , Dióxido de Silício , Propriedades de Superfície , Resíduos
12.
Genet Mol Res ; 14(4): 16431-7, 2015 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-26662440

RESUMO

Like other developing countries, China was reported to have a relatively high seroprevalence of anti-hepatitis A antibodies (anti-HAV). However, no studies have evaluated the prevalence of anti-HAV and HAV RNA among voluntary blood donors with or without elevated serum alanine transaminase (ALT) levels. Anti-HAV antibodies were detected using an enzyme-linked immunosorbent assay, and reverse transcription quantitative polymerase chain reaction was carried out for detection of HAV RNA. In the current study, we analyzed a total of 450 serum samples with elevated ALT levels (≥40 U/L) and 278 serum samples with non-elevated ALT levels. Seroprevalence rates of anti-HAV were 51.6% in donors with elevated ALT and 41.4% in donors with non-elevated ALT; however, none of the samples was positive for HAV RNA. The results of our study showed lower seroprevalence rates of anti-HAV in blood donors (irrespective of ALT levels) than those in published data on Chinese populations. Although donors with elevated ALT had statistically higher prevalence rates of anti- HAV than did those with non-elevated ALT, none of the serum samples had detectable levels of the active virus. In conclusion, our results demonstrate that the transmission of hepatitis A by blood transfusion will occur rarely.


Assuntos
Vírus da Hepatite A Humana/imunologia , Hepatite A/epidemiologia , Hepatite A/imunologia , Adolescente , Adulto , China/epidemiologia , Feminino , Hepatite A/virologia , Anticorpos Anti-Hepatite A/sangue , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Carga Viral , Adulto Jovem
13.
Genet Mol Res ; 14(1): 2785-92, 2015 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-25867427

RESUMO

MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in posttranscriptional regulation of target genes. miRNAs are involved in multiple biological processes by degrading targeted mRNAs or repressing mRNA translation in various organisms. Their conserved nature in various organisms makes them a good source of new miRNA discovery using comparative genomic approaches. In the present study, conserved Nile tilapia (Oreochromis niloticus) miRNAs were identified using a bioinformatic strategy based on expressed sequence tag and genome survey sequence databases. A total of 21 new miRNAs were detected and were found to belong to 17 families. Using mature miRNA sequences as queries, potential targets for tilapia miRNAs were predicted using a local BLAST program and the miRanda software. Target proteins identified using miRanda and BLAST analyses included transcription factors and molecules important in metabolism, transportation, immunity, stress-related activity, growth, and development. These miRNAs and their targets in tilapia may increase the understanding of the role of miRNAs in regulating the growth and development of tilapia.


Assuntos
Ciclídeos/genética , Biologia Computacional/métodos , Proteínas de Peixes/genética , MicroRNAs/genética , Animais , Sequência de Bases , Sequência Conservada/genética , Bases de Dados de Ácidos Nucleicos , Etiquetas de Sequências Expressas , RNA Mensageiro/genética , Software
14.
Eur J Pain ; 18(9): 1231-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24737575

RESUMO

BACKGROUND: One of the major unresolved issues in treating pain is the paradoxical hyperalgesia produced by opiates, and accumulating evidence implicate that EphBs receptors and ephrinBs ligands are involved in mediation of spinal nociceptive information and central sensitization, but the manner in which ephrinB/EphB signalling acts on spinal nociceptive information networks to produce hyperalgesia remains enigmatic. The objective of this research was to investigate the role of ephrinB/EphB signalling in remifentanil-induced hyperalgesia (RIH) and its downstream effector. METHODS: We characterized the remifentanil-induced pain behaviours by evaluating thermal hyperalgesia and mechanical allodynia in a rat hind paw incisional model. Protein expression of EphB1 receptor and ephrinB1 ligand in spinal dorsal horn cord was determined by Western blotting, and Fos was determined by immunohistochemistry assay, respectively. To figure out the manner in which ephrinB/EphB signalling acts with N-methyl-d-aspartic acid (NMDA) receptor, we used MK-801, an antagonist of NMDA receptor, trying to suppressed the hyperalgesia induced by ephrinB1-Fc, an agonist of ephrinB/EphB. RESULTS: Continuing infusion of remifentanil produced a thermal hyperalgesia and mechanical allodynia, which was accompanied with increased protein expression of spinal-level EphB1 receptor, ephrinB1 ligand and Fos; what appeared above was suppressed by pretreatment with EphB1-Fc, an antagonist of ephrinB/EphB or MK-801, and increased pain behaviours induced by intrathecal injection of ephrinB1-Fc, an agonist of ephrinB/EphB, were suppressed by MK-801. CONCLUSIONS: Our findings indicated that ephrinB/EphB signalling is involved in RIH. EphrinB/EphB signalling might be the upstream of NMDA receptor.


Assuntos
Analgésicos Opioides/farmacologia , Efrina-B1/metabolismo , Hiperalgesia/induzido quimicamente , Piperidinas/farmacologia , Receptor EphB1/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais/fisiologia , Analgésicos Opioides/efeitos adversos , Animais , Modelos Animais de Doenças , Maleato de Dizocilpina/farmacologia , Efrina-B1/agonistas , Efrina-B1/antagonistas & inibidores , Antagonistas de Aminoácidos Excitatórios/farmacologia , Masculino , Piperidinas/efeitos adversos , Ratos , Ratos Sprague-Dawley , Receptor EphB1/agonistas , Receptor EphB1/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Remifentanil
15.
Oncogene ; 33(14): 1799-808, 2014 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-23644656

RESUMO

Heparan sulfate proteoglycans are an important and abundant component of the extracellular matrix, which undergo substantial remodeling throughout tumorigenesis via the enzymatic activity of heparanase. Heparanase has been shown to be upregulated in many human cancers; however, its specific functions in human pancreatic neuroendocrine tumors (PanNETs) and spontaneous mouse models of cancer have not been evaluated. Here, we investigated the role of heparanase in PanNETs using patient samples and the RIP1-Tag2 (RT2) PanNET-transgenic mouse model. High heparanase expression significantly correlated with more advanced tumor stage, higher tumor grade and the presence of distant metastasis in PanNET patients. We genetically manipulated heparanase levels in the RT2 model using heparanase-transgenic mice, which constitutively overexpress heparanase, and heparanase-knockout mice. Heparanase was found to have a critical role in promoting tumor invasion, through both macrophage and cancer cell sources in the tumor microenvironment. In addition, elevated heparanase levels significantly increased peritumoral lymphangiogenesis in vivo and promoted the trans-differentiation of macrophages into lymphatic endothelial cell-like structures in culture. Conversely, we found that heparanase deletion led to increased angiogenesis and pericyte coverage. Together, these data identify important roles for heparanase in regulating several critical aspects of tumorigenesis, demonstrating that heparanase represents a potential therapeutic target for PanNET patients.


Assuntos
Glucuronidase/metabolismo , Linfangiogênese/genética , Tumores Neuroendócrinos/enzimologia , Neoplasias Pancreáticas/enzimologia , Animais , Progressão da Doença , Feminino , Citometria de Fluxo , Proteínas Ativadoras de GTPase/metabolismo , Glucuronidase/genética , Proteoglicanas de Heparan Sulfato/química , Humanos , Imuno-Histoquímica , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Invasividade Neoplásica , Neovascularização Patológica , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia
16.
Pharmacogenomics J ; 13(4): 342-8, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22491017

RESUMO

The 5-year survival rate for gastric adenocarcinoma (GA) remains only 40% and biomarkers to identify patients at high risk of tumor recurrence are urgently needed. Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix glycoprotein that mediates cell matrix interactions, and upregulation of SPARC can promote tumor progression and metastasis. This study investigated whether single-nucleotide polymorphisms (SNPs) in SPARC impact the prognosis of GA. Blood or formalin-fixed, paraffin-embedded tissues were obtained from 137 GA patients at the University of Southern California and Memorial Sloan-Kettering Cancer Center medical facilities. DNA was isolated and five SNPs in the SPARC 3'-untranslated region (UTR) were evaluated by DNA sequencing or PCR-restriction fragment length polymorphism. Associations between SNPs and time to tumor recurrence (TTR) were analyzed using Kaplan-Meier curves, log-rank tests, and likelihood-ratio test within logistic or Cox regression model as appropriate. Patients carrying at least one G allele of the SPARC rs1059829 polymorphism (GG, AG) showed a median TTR of 3.7 years compared with 2.1 years TTR for patients with AA (hazard ratio (HR) 0.57; P=0.033). In a multivariate analysis adjusted for T and N category as covariates and stratified by race, hospital and chemotherapy, patients with at least one SPARC rs1059829 G allele (GG, AG) remained significantly associated with superior TTR than patients with AA genotype (adjusted P=0.026). In addition, patients harboring the G-A-A haplotype had the highest risk of tumor recurrence (HR 1.892; adjusted P=0.016). Our findings suggest that SPARC 3'-UTR SNPs may be useful in predicting GA patients at increased risk of recurrence.


Assuntos
Recidiva Local de Neoplasia/genética , Osteonectina/genética , Prognóstico , Neoplasias Gástricas/genética , Idoso , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/patologia
17.
Eur J Radiol ; 82(1): 85-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23088880

RESUMO

PURPOSE: To describe the clinical and CT imaging features of goblet cell carcinoid (GCC) neoplasm of the appendix. METHODS AND MATERIALS: A computer search of pathology and radiology records over a 19-year period at our two institutions was performed using the search string "goblet". In the patients with appendiceal GCC neoplasms who had abdominopelvic CT, imaging findings were categorized, blinded to gross and surgical description, as: "Appendicitis", "Prominent appendix without peri-appendiceal infiltration", "Mass" or "Normal appendix". The CT appearance was correlated with an accepted pathological classification of: low grade GCC, signet ring cell adenocarcinoma ex, and poorly differentiated adenocarcinoma ex GCC group. RESULTS: Twenty-seven patients (age range, 28-80 years; mean age, 52 years; 15 female, 12 male) with pathology-proven appendiceal GCC neoplasm had CT scans that were reviewed. Patients presented with acute appendicitis (n=12), abdominal pain not typical for appendicitis (n=14) and incidental finding (n=1). CT imaging showed 9 Appendicitis, 9 Prominent appendices without peri-appendiceal infiltration, 7 Masses and 2 Normal appendices. Appendicitis (8/9) usually correlated with typical low grade GCC on pathology. In contrast, the majority of Masses and Prominent Appendices without peri-appendiceal infiltration were pathologically confirmed to be signet ring cell adenocarcinoma ex GCC. Poorly differentiated adenocarcinoma ex GCC was seen in only a small minority of patients. Hyperattenuation of the appendiceal neoplasm was seen in a majority of cases. CONCLUSIONS: GCC neoplasm of the appendix should be considered in the differential diagnosis in patients with primary appendiceal malignancy. Our cases demonstrated close correlation between our predefined CT pattern and the pathological classification.


Assuntos
Neoplasias do Apêndice/diagnóstico por imagem , Tumor Carcinoide/diagnóstico por imagem , Radiografia Abdominal/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Ann Oncol ; 23(10): 2656-2662, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22689179

RESUMO

BACKGROUND: To determine whether human epidermal growth factor receptor 2 (HER2) status is an independent prognostic factor in metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tumor samples from 381 metastatic gastric/GEJ cancer patients enrolled at Krankenhaus Nordwest and Memorial Sloan-Kettering Cancer Centers on six first-line trials of chemotherapy without trastuzumab were examined for HER2 by immunohistochemistry (IHC) and in situ hybridization (ISH). IHC 3+ or ISH-positive tumors were considered HER2 positive. RESULTS: Seventy-eight of 381 patients (20%) had HER2-positive disease. In the multivariate logistic model, there were significantly higher rates of HER2 positivity in patients with liver metastasis (liver metastasis 31%; no liver metastasis 11%; P = 0.025) and intestinal histology (intestinal 33%; diffuse/mixed 8%; P = 0.001). No significant differences in HER2 positivity were found between resections and biopsies or primaries and metastases. Patients with HER2-positive gastric cancer had longer median overall survival compared with HER2-negative gastric cancer patients (13.9 versus 11.4 months, P = 0.047), but multivariate analysis indicated that HER2 status was not an independent prognostic factor (hazard ratio 0.79; 0.44-1.14; P = 0.194). CONCLUSIONS: Approximately 20% of Western patients with metastatic gastric cancer are HER2 positive. Unlike breast cancer, HER2 positivity is not independently prognostic of patient outcome in metastatic gastric or GEJ.


Assuntos
Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Metástase Neoplásica , Neoplasias Gástricas/patologia , Neoplasias Esofágicas/metabolismo , Europa (Continente) , Humanos , Imuno-Histoquímica , Hibridização In Situ , Prognóstico , Neoplasias Gástricas/metabolismo , Estados Unidos
19.
Eur J Surg Oncol ; 38(4): 319-25, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22261085

RESUMO

BACKGROUND: While it is suggested that more than 15 lymph nodes (LNs) should be evaluated for accurate staging of gastric cancer, LN yield in western countries is generally low. The effect of preoperative chemotherapy on LN yield in gastric cancer is unknown. The aim of the present study is to determine whether preoperative chemotherapy is associated with any difference in the number of LNs obtained from specimens of patients who underwent curative surgery for gastric adenocarcinoma. PATIENTS AND METHODS: In 1205 patients from Memorial Sloan-Kettering Cancer Center (MSKCC) and 1220 patients from the Netherlands Cancer Registry (NCR) who underwent a gastrectomy with curative intent for gastric adenocarcinoma without receiving preoperative radiotherapy, LN yield was analyzed, comparing patients who received preoperative chemotherapy and patients who received no preoperative therapy. RESULTS: Of the 2425 patients who underwent a gastrectomy, 14% received preoperative chemotherapy. Median LN yields were 23 at MSKCC and 10 in the NCR. Despite this twofold difference in LN yield between the two populations, with multivariate Poisson regression, chemotherapy was not associated with LN yield of either population. Variables associated with increased LN yield were institution, female sex, lower age, total (versus distal) gastrectomy and increasing T-stage. CONCLUSIONS: In this patient series, treatment at MSKCC, female sex, lower age, total gastrectomy and increasing primary tumor stage were associated with a higher number of evaluated LNs. Preoperative chemotherapy was not associated with a decrease in LN yield. Evaluating more than 15 LNs after gastrectomy is feasible, with or without preoperative chemotherapy.


Assuntos
Adenocarcinoma/tratamento farmacológico , Terapia Neoadjuvante , Biópsia de Linfonodo Sentinela , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Quimioterapia Adjuvante , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Países Baixos , Cidade de Nova Iorque , Sistema de Registros , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
20.
Oncogene ; 31(11): 1459-67, 2012 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21822305

RESUMO

Tumor-associated macrophages have recently emerged as a key regulatory cell type during cancer progression, and have been found to promote tumor malignancy in the majority of studies performed to date. We show in this study that CD68(+) macrophages positively correlate with tumor grade and liver metastasis in human pancreatic neuroendocrine tumors (PNETs). To investigate the potential mechanisms whereby macrophages can promote PNET progression, we crossed the RIP1-Tag2 (RT2) mouse model of pancreatic islet cancer to colony-stimulating factor-1 (CSF-1)-deficient Csf1(op/op) mice, which have reduced numbers of tissue macrophages. Csf1(op/op) RT2 mice had a substantial reduction in cumulative tumor burden, which interestingly resulted from a significant decrease in angiogenic switching and tumor number, rather than an evident effect on tumor growth. In the tumors that did develop in CSF-1-deficient animals, however, there were no significant differences in tumor cell proliferation, apoptosis, angiogenesis or invasion. CSF-1 deficiency decreased macrophage infiltration by approximately 50% during all stages of RT2 tumor progression. Interestingly, several cytokines were upregulated in CSF-1-deficient RT2 tumors, and neutrophil infiltration was increased. These results show that macrophages are important for promoting PNET development and suggest that additional factors contribute to the recruitment and survival of myeloid cells in RT2 tumors in the absence of CSF-1.


Assuntos
Fator Estimulador de Colônias de Macrófagos/deficiência , Macrófagos/metabolismo , Tumores Neuroendócrinos/genética , Neoplasias Pancreáticas/genética , Adenoma de Células das Ilhotas Pancreáticas/genética , Adenoma de Células das Ilhotas Pancreáticas/patologia , Animais , Humanos , Camundongos , Camundongos Transgênicos , Neoplasias Pancreáticas/patologia
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