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1.
Polymers (Basel) ; 13(23)2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34883615

RESUMO

In the present study, cylindrical ABS P400 polymer parts (diameter 6.5 mm) to be used as die-sinking EDM (electric discharge machining) novel electrodes were fabricated using a fused deposition modeling (FDM) process. To meet the conductivity requirement in EDM, ABS parts were metallized using an innovative method that comprised putting aluminum-charcoal (Al-C) on them followed by their copper electroplating. Real-time EDM of the mild steel workpiece was performed using novel electrodes, and machining performance of the electrodes, measured in terms of dimensional accuracy, i.e., change in diameter (ΔD) and change in depth (ΔH) of the cavity, under varying levels of three EDM factors, i.e., current (I), pulse on time (Ton), and pulse off time (Toff), was investigated. Machining results were analyzed using analysis of variance (ANOVA), perturbation graphs, and 3D surface plots. The optimal setting of the EDM parameters for minimizing ΔD and ΔH was determined using the desirability function approach. The suitability of the novel electrodes for EDM was ascertained by comparing their machining results with those of solid copper (SC) electrodes and electrodes fabricated by FDM and metallized using the electro-deposition method (FDM-EM), already reported in the literature, under similar machining conditions. From the results, it was found that ΔD and ΔH were less when EDM was performed using novel electrodes.

2.
Arab J Sci Eng ; : 1-19, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34815927

RESUMO

The share of wind-based electricity generation is gradually increasing in the world energy market. Wind energy can reduce dependency on fossil fuels, as the result being attributed to a decrease in global warming. This paper discusses and reviews the basic principle parameters that affect the performance of wind turbines. An overview presents the introduction and the background of energy consumption, following the order of the elaboration of wind turbines, including mathematical models, categories of wind turbines were critically discussed. Moreover, it also focuses on materials that are commonly considered for wind turbine manufacturing, and the process used to recycle them. The scale of recycling methods for fiberglass and thermoplastic is presented in the respective section. Various parameters that reduce the function of wind turbines are explained in depth. This review also discusses various environmental impacts of wind turbines. Future research studies are suggested in the conclusion section.

3.
Transl Oncol ; 14(12): 101229, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34592589

RESUMO

Tumour metastasis accounts for over 90% of cancer related deaths. The platelet is a key blood component, which facilitates efficient metastasis. This study aimed to understand the molecular mechanisms involved in tumour-platelet cell interactions. The interaction between cancer cells and platelets was examined in 15 epithelial cell lines, representing 7 cancer types. Gene expression analysis of EMT-associated and cancer stemness genes was performed by RT-PCR. Whole transcriptome analysis (WTA) was performed using Affymetrix 2.0ST arrays on a platelet co-cultured ovarian model. Platelet adhesion and activation occurred across all tumour types. WTA identified increases in cellular movement, migration, invasion, adhesion, development, differentiation and inflammation genes and decreases in processes associated with cell death and survival following platelet interaction. Increased invasive capacity was also observed in a subset of cell lines. A cross-comparison with a platelet co-cultured mouse model identified 5 common altered genes; PAI-1, PLEK2, CD73, TNC, and SDPR. Platelet cancer cell interactions are a key factor in driving the pro-metastatic phenotype and appear to be mediated by 5 key genes which have established roles in metastasis. Targeting these metastasis mediators could improve cancer patient outcomes.

4.
Mol Cancer ; 20(1): 59, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789677

RESUMO

Cancer cells that transit from primary tumours into the circulatory system are known as circulating tumour cells (CTCs). These cancer cells have unique phenotypic and genotypic characteristics which allow them to survive within the circulation, subsequently extravasate and metastasise. CTCs have emerged as a useful diagnostic tool using "liquid biopsies" to report on the metastatic potential of cancers. However, CTCs by their nature interact with components of the blood circulatory system on a constant basis, influencing both their physical and morphological characteristics as well as metastatic capabilities. These properties and the associated molecular profile may provide critical diagnostic and prognostic capabilities in the clinic. Platelets interact with CTCs within minutes of their dissemination and are crucial in the formation of the initial metastatic niche. Platelets and coagulation proteins also alter the fate of a CTC by influencing EMT, promoting pro-survival signalling and aiding in evading immune cell destruction. CTCs have the capacity to directly hijack immune cells and utilise them to aid in CTC metastatic seeding processes. The disruption of CTC clusters may also offer a strategy for the treatment of advance staged cancers. Therapeutic disruption of these heterotypical interactions as well as direct CTC targeting hold great promise, especially with the advent of new immunotherapies and personalised medicines. Understanding the molecular role that platelets, immune cells and the coagulation cascade play in CTC biology will allow us to identify and characterise the most clinically relevant CTCs from patients. This will subsequently advance the clinical utility of CTCs in cancer diagnosis/prognosis.


Assuntos
Coagulação Sanguínea , Plaquetas/metabolismo , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Animais , Biomarcadores , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Comunicação Celular/genética , Comunicação Celular/imunologia , Gerenciamento Clínico , Suscetibilidade a Doenças , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/imunologia , Humanos , Neoplasias/sangue , Neoplasias/complicações , Neoplasias/etiologia , Neoplasias/patologia
5.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20248966

RESUMO

OBJECTIVESTo determine risk factors for death in patients with COVID-19 admitted to the main public sector hospital in Somalia and identify interventions contributing to improved clinical outcome in a low-resource and fragile setting. SETTINGMain public sector tertiary hospital in Mogadishu, Somalia. PARTICIPANTSAll 131 laboratory-confirmed COVID-19 patients admitted to the main public tertiary hospital in Somalia between 30 March and 12 June 2020. MAIN OUTCOME MEASURESWe extracted demographic and clinical data from hospital records of all 131 COVID-19 patients admitted to hospital until their death or recovery. We used Kaplan-Meier statistics to estimate survival probabilities and the log-rank test to assess significant differences in survival between groups. We used the Cox proportional hazard model to estimate likelihood of death and assess the effect of risk factors on survival. RESULTSOf the 131 patients, 52 (40%) died in the hospital and 79 (60%) survived to discharge. The factors independently associated with increased risk of in-hospital death were: age [≥] 60 years - survival probability on day 21 in patients < 60 years was 0.789 (95% confidence interval (CI): 0.658-0.874) compared with 0.339 (95% CI: 0.205-0.478) in patients [≥] 60 years; cardiovascular disease (survival probability 0.478 (95% CI: 0.332-0.610) in patients with cardiovascular disease compared with 0.719 (95% CI: 0.601-0.807) in patients without cardiovascular disease); and non-invasive ventilation on admission - patients who were not ventilated were significantly more likely to survive than those who were (P < 0.001). CONCLUSIONOur study, which includes the largest cohort of COVID-19 patients admitted to a single hospital in a sub-Saharan African country, confirms that underlying conditions and age are associated with increased risk of in-hospital death in patients with COVID-19. Our results show the advantage of medical oxygen over non-invasive ventilation in the treatment of patients with severe COVID-19 symptoms.

6.
IDCases ; 23: e01008, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33294371

RESUMO

Mediastinal involvement of hydatidosis is rare even in endemic areas. Isolated mediastinal without lung or liver involvement is even less commonly reported. We present the case of a young gentleman who was diagnosed with primary mediastinal hydatidosis based on clinical, radiological and pathological criteria. He underwent successful resection of the lesion by VATS (Video-assisted thoracoscopic surgery) preceded by two weeks of medical treatment with albendazole and had an excellent outcome. To the best of our knowledge, this is the first reported case in the state of Qatar.

7.
Breast Cancer Res Treat ; 181(3): 571-580, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32378053

RESUMO

PURPOSE: The association between pathological complete response (pCR) in patients receiving neoadjuvant chemotherapy (NAC) for breast cancer and Circulating Tumour Cells (CTCs) is not clear. The aim of this study was to assess whether CTC enumeration could be used to predict pathological response to NAC in breast cancer as measured by the Miller-Payne grading system. METHODS: Twenty-six patients were recruited, and blood samples were taken pre- and post-NAC. CTCs were isolated using the ScreenCell device and stained using a modified Giemsa stain. CTCs were enumerated by 2 pathologists and classified as single CTCs, doublets, clusters/microemboli and correlated with the pathological response as measured by the Miller-Payne grading system. χ2 or ANOVA was performed in SPSS 24.0 statistics software for associations. RESULTS: 89% of patients had invasive ductal carcinoma (IDC) and 11% invasive lobular carcinoma (ILC). At baseline 85% of patients had CTCs present, median 7 (0-161) CTCs per 3 ml of whole blood. Post-chemotherapy, 58% had an increase in CTCs. This did not correlate with the Miller-Payne grade of response. No significant association was identified between the number of CTCs and clinical characteristics; however, we did observe a correlation between pre-treatment CTC counts and body mass index, p < 0.05. CONCLUSIONS: Patients with a complete response to NAC still had CTCs present, suggesting enumeration is not sufficient to aid surgery stratification. Additional characterisation and larger studies are needed to further characterise CTCs isolated pre- and post-chemotherapy. Long-term follow-up of these patients will determine the significance of CTCs in NAC breast cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Terapia Neoadjuvante/mortalidade , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/metabolismo , Estudos de Coortes , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Células Neoplásicas Circulantes/efeitos dos fármacos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida
8.
Sci Rep ; 8(1): 679, 2018 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-29330439

RESUMO

Citrullination, or the post-translational deimination of polypeptide-bound arginine, is involved in several pathological processes in the body, including autoimmunity and tumorigenesis. Recent studies have shown that nanomaterials can trigger protein citrullination, which might constitute a common pathogenic link to disease development. Here we demonstrated auto-antibody production in serum of nanomaterials-treated mice. Citrullination-associated phenomena and PAD levels were found to be elevated in nanomaterials -treated cell lines as well as in the spleen, kidneys and lymph nodes of mice, suggesting a systemic response to nanomaterials injection, and validated in human pleural and pericardial malignant mesothelioma (MM) samples. The observed systemic responses in mice exposed to nanomaterials support the evidence linking exposure to environmental factors with the development of autoimmunity responses and reinforces the need for comprehensive safety screening of nanomaterials. Furthermore, these nanomaterials induce pathological processes that mimic those observed in Pleural MM, and therefore require further investigations into their carcinogenicity.


Assuntos
Autoanticorpos/sangue , Hidrolases/metabolismo , Nanofios/administração & dosagem , Níquel/química , Proteínas/metabolismo , Células A549 , Animais , Formação de Anticorpos , Linhagem Celular Tumoral , Citrulinação , Feminino , Humanos , Hidrolases/imunologia , Rim/metabolismo , Rim/patologia , Linfonodos/metabolismo , Linfonodos/patologia , Mesotelioma/metabolismo , Mesotelioma/patologia , Camundongos , Camundongos Endogâmicos C57BL , Nanofios/química , Baço/metabolismo , Baço/patologia
9.
J Orthop Trauma ; 32 Suppl 1: S66-S71, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29373455

RESUMO

INTRODUCTION: There is no consensus regarding the postoperative radiology imaging protocol after pelvic fracture surgery. Some institutes routinely scan all patients after their surgery, others do not. The aim of this study was to assess the value of routine use of computed tomography (CT) scans after pelvic fracture surgery and to determine the sensitivity of conventional plain radiographs and intraoperative fluoroscopy in detecting metalwork malposition. PATIENTS AND METHODS: The radiographs and clinical notes of patients undergoing pelvic fracture surgery in the period between January 2010 and December 2015 were reviewed. Patients were categorized into 2 main groups: group A-patients whose fixation entailed the use of a sacroiliac (SI) screws and group B-patients whose fixation did not require an SI screw. Furthermore, the patients were classified according to the position of metalwork in their postoperative plain radiographs and perioperative fluoroscopy into 3 groups: (1) Safe: When there was no suspicion of metalwork malposition. (2) Suspicious: When there was some suspicion of malposition but radiographs were inconclusive. (3) Definite: When plain imaging showed a definite malposition. RESULTS: One hundred ninety-eight patients were included in this study (161 in group A and 37 in group B). In group A, 148 (92%) were classified as safe, 10 were suspicious (6%), and 3 (2%) showed definite malposition. Of the fractures that were believed to be safe on plain radiographs, 78% were confirmed to be safe on CT scans, whereas 22% showed malpositioned metalwork, and 7 patients (4%) required a revision surgery. Plain radiographs showed a sensitivity of 27% in detecting metalwork malposition and a specificity of 99%. Increasing the number of screws significantly increased the risk of malposition and reoperation (P = 0.006 and 0.002 respectively). The plain images of group B were all classified as safe. The CT scans detected 2 cases with long metalwork protruding into the soft tissues, none of which required a revision surgery. CONCLUSION: Perioperative fluoroscopy and plain postoperative radiographs have a low sensitivity in detecting the metalwork malposition after pelvic fracture surgery. We recommend the use of routine postoperative CT scans in patients whose fixation entails the use of SI screws. In this series, routine scanning of patients who did not have SI screws added no significant clinical value. LEVEL OF EVIDENCE: Level IV Diagnostic. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Fixação Interna de Fraturas/métodos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Ossos Pélvicos/lesões , Cuidados Pós-Operatórios/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Fixação Interna de Fraturas/efeitos adversos , Consolidação da Fratura/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Procedimentos Desnecessários/estatística & dados numéricos , Adulto Jovem
10.
Toxicol Sci ; 150(1): 40-53, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26612840

RESUMO

Amorphous silica nanoparticles (ASNP) can be synthetized via several processes, 2 of which are the thermal route (to yield pyrogenic silica) and the wet route from a solution containing silicate salts (to obtain precipitated, colloidal, mesoporous silica, or silica gel). Both methods of synthesis lead to ASNP that are applied as food additive (E551). Current food regulation does not require that production methods of additives are indicated on the product label, and, thus, the ASNP are listed without mentioning the production method. Recent results indicate, however, that pyrogenic ASNP are more cytotoxic than ASNP synthesized through the wet route. The present study was aimed at clarifying if 2 representative preparations of ASNP, NM-203 (pyrogenic) and NM-200 (precipitated), of comparable size, specific surface area, surface charge, and hydrodynamic radius in complete growth medium, had different effects on 2 murine macrophage cell lines (MH-S and RAW264.7 cells). Our results show that, when incubated in protein-rich fluids, NM-203 adsorbed on their surface more proteins than NM-200 and, once incubated with macrophages, elicited a greater oxidative stress, assessed from Hmox1 induction and ROS production. Flow cytometry and helium ion microscopy indicated that pyrogenic NM-203 interacted with macrophages more strongly than the precipitated NM-200 and triggered a more evident inflammatory response, evaluated with Nos2 induction, NO production and the secretion of TNF-α, IL-6 and IL-1ß. Moreover, both ASNP synergized macrophage activation by bacterial lipopolysaccharide (LPS), with a higher effect observed for NM-203. In conclusion, the results presented here demonstrate that, compared to precipitated, pyrogenic ASNP exhibit enhanced interaction with serum proteins and cell membrane, and cause a larger oxidative stress and stronger proinflammatory effects in macrophages. Therefore, these 2 nanomaterials should not be considered biologically equivalent.


Assuntos
Imunidade Inata/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Nanopartículas/toxicidade , Dióxido de Silício/toxicidade , Animais , Técnicas de Cultura de Células , Linhagem Celular , Precipitação Química , Citocinas/genética , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Citometria de Fluxo , Macrófagos Alveolares/imunologia , Camundongos , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Nanopartículas/metabolismo , Nanotecnologia/métodos , Óxido Nítrico/biossíntese , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício/química , Dióxido de Silício/metabolismo , Propriedades de Superfície
11.
Methods Mol Biol ; 1326: 67-77, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26498614

RESUMO

The IN Cell Analyzer 1000 possesses several distinguishing features that make it a valuable tool in research today. This fully automated high content screening (HCS) system introduced quantitative fluorescent microscopy with computerized image analysis for use in cell-based analysis. Previous studies have focused on live cell assays, where it has proven to be a powerful and robust method capable of providing reproducible, quantitative data. Using HCS as a tool to investigate antigen expression in duodenal biopsies, we developed a novel approach to tissue positioning and mapping. We adapted IN Cell Analyzer 1000's image acquisition and analysis software for the investigation of tissue transglutaminase (tTG) and smooth muscle alpha-actin (SM α-actin) staining in paraffin-embedded duodenal tissue sections from celiac patients and healthy controls. These innovations allowed a quantitative analysis of cellular structure and protein expression. The results from routine biopsy material indicated the intensity of protein expression was altered in celiac disease compared to normal biopsy material.


Assuntos
Doença Celíaca/patologia , Biópsia , Humanos , Microscopia de Fluorescência
12.
Nanomedicine ; 11(4): 815-24, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25652898

RESUMO

UNLABELLED: Bismuth Ferrite (BFO) nanoparticles (BFO-NP) display interesting optical (nonlinear response) and magnetic properties which make them amenable for bio-oriented diagnostic applications as intra- and extra membrane contrast agents. Due to the relatively recent availability of this material in well dispersed nanometric form, its biocompatibility was not known to date. In this study, we present a thorough assessment of the effects of in vitro exposure of human adenocarcinoma (A549), lung squamous carcinoma (NCI-H520), and acute monocytic leukemia (THP-1) cell lines to uncoated and poly(ethylene glycol)-coated BFO-NP in the form of cytotoxicity, haemolytic response and biocompatibility. Our results support the attractiveness of the functional-BFO towards biomedical applications focused on advanced diagnostic imaging. FROM THE CLINICAL EDITOR: Bismuth Ferrite nanoparticles (BFO-NP) have been recently successfully introduced as photodynamic tools and imaging probes. However, how these nanoparticles interact with various cells at the cellular level remains poorly understood. In this study, the authors performed in vitro experiments to assess the effects of uncoated and PEG-coated BFO-NP in the form of cytotoxicity, haemolytic response and biocompatibility.


Assuntos
Bismuto/química , Materiais Revestidos Biocompatíveis/química , Meios de Contraste/química , Compostos Férricos/química , Teste de Materiais , Nanopartículas/química , Linhagem Celular Tumoral , Humanos
13.
ACS Nano ; 8(6): 5682-95, 2014 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-24873349

RESUMO

Despite the widespread availability of immunohistochemical and other methodologies for screening and early detection of lung and breast cancer biomarkers, diagnosis of the early stage of cancers can be difficult and prone to error. The identification and validation of early biomarkers specific to lung and breast cancers, which would permit the development of more sensitive methods for detection of early disease onset, is urgently needed. In this paper, ultra-small and bright nanoprobes based on quantum dots (QDs) conjugated to single domain anti-HER2 (human epidermal growth factor receptor 2) antibodies (sdAbs) were applied for immunolabeling of breast and lung cancer cell lines, and their performance was compared to that of anti-HER2 monoclonal antibodies conjugated to conventional organic dyes Alexa Fluor 488 and Alexa Fluor 568. The sdAbs-QD conjugates achieved superior staining in a panel of lung cancer cell lines with differential HER2 expression. This shows their outstanding potential for the development of more sensitive assays for early detection of cancer biomarkers.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias Pulmonares/metabolismo , Pontos Quânticos , Receptor ErbB-2/metabolismo , Anticorpos/química , Anticorpos Monoclonais/química , Linhagem Celular Tumoral , Técnicas de Cocultura , Citometria de Fluxo , Corantes Fluorescentes/química , Humanos , Imuno-Histoquímica , Macrófagos/metabolismo , Microscopia Confocal
14.
Br J Cancer ; 110(1): 94-106, 2014 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-24196790

RESUMO

BACKGROUND: Emerging studies have shown the potential benefit of arming oncolytic viruses with therapeutic genes. However, most of these therapeutic genes are placed under the regulation of ubiquitous viral promoters. Our goal is to generate a safer yet potent oncolytic herpes simplex virus type-1 (HSV-1) for cancer therapy. METHODS: Using bacterial artificial chromosome (BAC) recombineering, a cell cycle-regulatable luciferase transgene cassette was replaced with the infected cell protein 6 (ICP6) coding region (encoded for UL39 or large subunit of ribonucleotide reductase) of the HSV-1 genome. These recombinant viruses, YE-PC8, were further tested for its proliferation-dependent luciferase gene expression. RESULTS: The ability of YE-PC8 to confer proliferation-dependent transgene expression was demonstrated by injecting similar amount of viruses into the tumour-bearing region of the brain and the contralateral normal brain parenchyma of the same mouse. The results showed enhanced levels of luciferase activities in the tumour region but not in the normal brain parenchyma. Similar findings were observed in YE-PC8-infected short-term human brain patient-derived glioma cells compared with normal human astrocytes. intratumoural injection of YE-PC8 viruses resulted in 77% and 80% of tumour regression in human glioma and human hepatocellular carcinoma xenografts, respectively. CONCLUSION: YE-PC8 viruses confer tumour selectivity in proliferating cells and may be developed further as a feasible approach to treat human cancers.


Assuntos
Neoplasias Encefálicas/terapia , Glioma/terapia , Herpesvirus Humano 1/fisiologia , Terapia Viral Oncolítica/métodos , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/virologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/virologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Chlorocebus aethiops , Feminino , Glioma/genética , Glioma/virologia , Herpesvirus Humano 1/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/virologia , Luciferases/genética , Camundongos , Camundongos Nus , Camundongos SCID , Elementos Reguladores de Transcrição , Transcrição Genética , Transgenes , Células Vero , Proteínas Virais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Thromb Res ; 132(5): 627-34, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24094893

RESUMO

INTRODUCTION: Ovarian cancer is known to display a particular association with venous thromboembolism (VTE) with reports up to 42% of patients developing thromboembolic complications. Tissue Factor (TF) and its inhibitor Tissue Factor Pathway Inhibitor (TFPI) have been implicated in VTE risk in cancer. The aim of this study was to measure tumour derived TF and TFPI and to investigate their potential role in VTE in ovarian cancer patients. METHODS: TF and TFPI mRNA expression was measured using TaqMan real time PCR in 99 ovarian tumour samples. Nineteen cases complicated by VTE were matched to 19 cases without VTE. TF and TFPI protein levels were measured using ELISA and immunohistochemistry was used to localize TF expression. The role of TF expression on overall survival was also determined. RESULTS: TF mRNA and protein expression was increased in tumours from patients with clear cell carcinoma (p<0.001). TF protein expression was also increased in endometroid carcinoma (P<0.01) compared with benign tumours. TFPI mRNA expression was increased in clear cell carcinoma (P<0.01). TF mRNA and antigen level was increased in malignant tumours of patients who developed VTE compared with matched malignant õtumours of patients who remained thrombosis free (P<0.01). There was no difference in TFPI expression between the two groups. CONCLUSION: TF expression in ovarian cancer is significantly higher in patients who develop VTE. TF expression was increased in clear cell ovarian cancer and endometroid cancer and this may explain the higher risk of VTE in these subgroups. TF derived from these tumours may be the trigger for VTE in ovarian cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica , Lipoproteínas/genética , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/genética , Tromboplastina/genética , Trombose Venosa/etiologia , Idoso , Feminino , Humanos , Imuno-Histoquímica , Lipoproteínas/análise , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Ovário/patologia , RNA Mensageiro/genética , Tromboplastina/análise , Regulação para Cima , Trombose Venosa/genética
16.
Sci Rep ; 3: 1124, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23350031

RESUMO

Single-walled carbon nanotubes (SWCNTs) have been widely explored as potential technologies for information systems and medical applications. The impact of SWCNTs on human health is of prime concern, if SWCNTs have a future in the manufacturing industry. This study proposes a novel, inflammation-independent paradigm of toxicity for SWCNTs, identifying the protein citrullination process as early-stage indicator of inflammatory responses of macrophages (THP-1) and of subtle phenotypic damages of lung epithelial (A549) cells following exposure to chemically-treated SWCNTs. Our results showed that, while most of the cellular responses of A549 cells exposed to SWCNTs are different to those of similarly treated THP-1 cells, the protein citrullination process is triggered in a dose- and time-dependent manner in both cell lines, with thresholds comparable between inflammatory (THP-1) and non-inflammatory (A549) cell types. The cellular mechanism proposed herein could have a high impact in predicting the current risk associated with environmental exposure to SWCNTs.


Assuntos
Permeabilidade da Membrana Celular/efeitos dos fármacos , Citrulina/metabolismo , Nanotubos de Carbono/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Nanotubos de Carbono/química
17.
Int J Mol Sci ; 14(1): 2085-103, 2013 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-23340649

RESUMO

Platinum resistance is a major cause of treatment failure in ovarian cancer. We previously identified matrix metalloproteinase 9 (MMP-9) as a potential therapeutic target of chemoresistant disease. A2780cis (cisplatin-resistant) and A2780 (cisplatin-sensitive) ovarian carcinoma cell lines were used. The cytotoxic effect of MMP-9/MMP-2 inhibitor, (2R)-2-[(4-Biphenylsulfonyl) amino]-3 phenylpropionic acid (C21H19NO4S) alone or in combination with cisplatin was determined using high content screening. Protein expression was examined using immunohistochemistry and ELISA. Co-incubation of cisplatin and an MMP-9/MMP-2 inhibitor, (2R)-2-[(4-Biphenylsulfonyl) amino]-3 phenylpropionic acid (C21H19NO4S) resulted in significantly greater cytotoxicity as compared to either treatment alone in a cisplatin resistant MMP-9 overexpressing cell line; A2780cis. In addition, pre-incubating with MMP-9i prior to cisplatin further enhances the cytotoxic effect. No significant difference was observed in MMP-9 protein in tissue but a trend towards increased MMP-9 was observed in recurrent serum. We propose that MMP-9/MMP-2i may be utilized in the treatment of recurrent/chemoresistant ovarian cancers that overexpress MMP-9 mRNA but its role in vivo remains to be evaluated.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Neoplasias , Inibidores de Proteases/farmacologia , Linhagem Celular Tumoral , Humanos , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo
18.
Nanomedicine (Lond) ; 7(8): 1181-95, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22625207

RESUMO

AIM: Rapidly expanding manufacture and use of nanomaterials emphasize the requirements for thorough assessment of health outcomes associated with novel applications. Post-translational protein modifications catalyzed by Ca(2+)-dependent peptidylargininedeiminases have been shown to trigger immune responses including autoantibody generation, a hallmark of immune complexes deposition in rheumatoid arthritis. Therefore, the aim of the study was to assess if nanoparticles are able to promote protein citrullination. MATERIALS & METHODS: Human A549 and THP-1 cells were exposed to silicon dioxide, carbon black or single-walled carbon nanotubes. C57BL/6 mice were exposed to respirable single-walled carbon nanotubes. Protein citrullination, peptidylargininedeiminases activity and target proteins were evaluated. RESULTS: The studied nanoparticles induced protein citrullination both in cultured human cells and mouse lung tissues. Citrullination occurred via the peptidylargininedeiminase-dependent mechanism. Cytokeratines 7, 8, 18 and plectins were identified as intracellular citrullination targets. CONCLUSION: Nanoparticle exposure facilitated post-translational citrullination of proteins.


Assuntos
Carbono/metabolismo , Citrulina/metabolismo , Nanoestruturas/administração & dosagem , Proteínas/metabolismo , Dióxido de Silício/metabolismo , Fuligem/metabolismo , Animais , Cálcio/metabolismo , Carbono/administração & dosagem , Linhagem Celular , Feminino , Humanos , Hidrolases/antagonistas & inibidores , Hidrolases/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Nanoestruturas/química , Nanotubos de Carbono/química , Processamento de Proteína Pós-Traducional , Desiminases de Arginina em Proteínas , Dióxido de Silício/administração & dosagem , Fuligem/administração & dosagem
19.
PLoS One ; 7(3): e30923, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22479306

RESUMO

Advancement of biomedical applications of carbonaceous nanomaterials is hampered by their biopersistence and pro-inflammatory action in vivo. Here, we used myeloperoxidase knockout B6.129X1-MPO (MPO k/o) mice and showed that oxidation and clearance of single walled carbon nanotubes (SWCNT) from the lungs of these animals after pharyngeal aspiration was markedly less effective whereas the inflammatory response was more robust than in wild-type C57Bl/6 mice. Our results provide direct evidence for the participation of MPO - one of the key-orchestrators of inflammatory response - in the in vivo pulmonary oxidative biodegradation of SWCNT and suggest new ways to control the biopersistence of nanomaterials through genetic or pharmacological manipulations.


Assuntos
Pulmão/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Peroxidase/deficiência , Animais , Líquido da Lavagem Broncoalveolar/citologia , Quimiocina CCL2/metabolismo , Feminino , Fibrose/induzido quimicamente , Fibrose/metabolismo , Interleucina-6/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Nanotubos de Carbono/ultraestrutura , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Oxirredução , Peroxidase/genética , Pneumonia/induzido quimicamente , Pneumonia/metabolismo , Análise Espectral Raman , Fator de Necrose Tumoral alfa/metabolismo
20.
J Nanobiotechnology ; 9: 29, 2011 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-21801388

RESUMO

BACKGROUND: Nanomaterials such as SiO2 nanoparticles (SiO2NP) are finding increasing applications in the biomedical and biotechnological fields such as disease diagnostics, imaging, drug delivery, food, cosmetics and biosensors development. Thus, a mechanistic and systematic evaluation of the potential biological and toxic effects of SiO2NP becomes crucial in order to assess their complete safe applicability limits. RESULTS: In this study, human monocytic leukemia cell line THP-1 and human alveolar epithelial cell line A549 were exposed to a range of amorphous SiO2NP of various sizes and concentrations (0.01, 0.1 and 0.5 mg/ml). Key biological indicators of cellular functions including cell population density, cellular morphology, membrane permeability, lysosomal mass/pH and activation of transcription factor-2 (ATF-2) were evaluated utilizing quantitative high content screening (HCS) approach and biochemical techniques. Despite the use of extremely high nanoparticle concentrations, our findings showed a low degree of cytotoxicity within the panel of SiO2NP investigated. However, at these concentrations, we observed the onset of stress-related cellular response induced by SiO2NP. Interestingly, cells exposed to alumina-coated SiO2NP showed low level, and in some cases complete absence, of stress response and this was consistent up to the highest dose of 0.5 mg/ml. CONCLUSIONS: The present study demonstrates and highlights the importance of subtle biological changes downstream of primary membrane and endocytosis-associated phenomena resulting from high dose SiO2NP exposure. Increased activation of transcription factors, such as ATF-2, was quantitatively assessed as a function of i) human cell line specific stress-response, ii) SiO2NP size and iii) concentration. Despite the low level of cytotoxicity detected for the amorphous SiO2NP investigated, these findings prompt an in-depth focus for future SiO2NP-cell/tissue investigations based on the combined analysis of more subtle signalling pathways associated with accumulation mechanisms, which is essential for establishing the bio-safety of existing and new nanomaterials.


Assuntos
Nanopartículas/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Dióxido de Silício/efeitos adversos , Estresse Fisiológico , Fator 2 Ativador da Transcrição/metabolismo , Óxido de Alumínio/efeitos adversos , Linhagem Celular , Permeabilidade da Membrana Celular/efeitos dos fármacos , Humanos , Lisossomos/efeitos dos fármacos
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