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1.
Clin Radiol ; 79(1): e41-e47, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37872026

RESUMO

AIM: To investigate the effect of deep learning on the diagnostic performance of radiologists and radiology residents in detecting breast cancers on computed tomography (CT). MATERIALS AND METHODS: In this retrospective study, patients undergoing contrast-enhanced chest CT between January 2010 and December 2020 using equipment from two vendors were included. Patients with confirmed breast cancer were categorised as the training (n=201) and validation (n=26) group and the testing group (n=30) using processed CT images from either vendor. The trained deep-learning model was applied to test group patients with (30 females; mean age = 59.2 ± 15.8 years) and without (19 males, 21 females; mean age = 64 ± 15.9 years) breast cancer. Image-based diagnostic performance of the deep-learning model was evaluated with the area under the receiver operating characteristic curve (AUC). Two radiologists and three radiology residents were asked to detect malignant lesions by recording a four-point diagnostic confidence score before and after referring to the result from the deep-learning model, and their diagnostic performance was evaluated using jackknife alternative free-response receiver operating characteristic analysis by calculating the figure of merit (FOM). RESULTS: The AUCs of the trained deep-learning model on the validation and test data were 0.976 and 0.967, respectively. After referencing with the result of the deep learning model, the FOMs of readers significantly improved (reader 1/2/3/4/5: from 0.933/0.962/0.883/0.944/0.867 to 0.958/0.968/0.917/0.947/0.900; p=0.038). CONCLUSION: Deep learning can help radiologists and radiology residents detect breast cancer on CT.


Assuntos
Neoplasias da Mama , Aprendizado Profundo , Radiologia , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias da Mama/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Radiologistas
2.
J Endocrinol Invest ; 45(12): 2313-2328, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35857218

RESUMO

PURPOSE: Pheochromocytoma crisis is a life-threatening endocrine emergency that requires prompt diagnosis and treatment. Because of its rarity, sudden onset, and lack of internationally uniform and validated diagnostic criteria, pheochromocytoma crisis remains to be fully clarified. Therefore, we aimed to describe the clinical characteristics and outcomes of pheochromocytoma crisis through a literature review. METHODS: We performed a systematic literature search of PubMed/MEDLINE database, Igaku-Chuo-Zasshi (Japanese database), and Google Scholar to identify case reports of pheochromocytoma crisis published until February 5, 2021. Information was extracted and analyzed from the literature that reported adequate individual patient data of pheochromocytoma crisis in English or Japanese. Cases were also termed as pheochromocytoma multisystem crisis (PMC) if patients had signs of hyperthermia, multiple organ failure, encephalopathy, and labile blood pressure. RESULTS: In the 200 cases of pheochromocytoma crisis identified from 187 articles, the mean patient age was 43.8 ± 15.5 years. The most common symptom was headache (39.5%). The heart was the most commonly damaged organ resulting from a complication of a pheochromocytoma crisis (99.0%), followed by the lungs (44.0%) and the kidney (21.5%). PMC accounted for 19.0% of all pheochromocytoma crisis cases. After excluding 12 cases with unknown survival statuses, the mortality rate was 13.8% (26/188 cases). Multivariable logistic regression analysis revealed that nausea and vomiting were significantly associated with a higher mortality rate. CONCLUSION: Pheochromocytoma can present with different symptomatology, affecting different organ systems. Clinicians should be aware that patients with nausea or vomiting are at a higher risk of death because of pheochromocytoma crisis.


Assuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Adulto , Humanos , Pessoa de Meia-Idade , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/terapia , Insuficiência de Múltiplos Órgãos/complicações , Náusea/complicações , Feocromocitoma/diagnóstico , Feocromocitoma/epidemiologia , Feocromocitoma/terapia , Vômito/complicações
3.
Int Nurs Rev ; 68(3): 399-411, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33459373

RESUMO

AIMS: To elucidate (i) the challenges and constraints in the development and implementation of the regulatory framework for nursing professionals in Cambodia and (ii) the specific strategies adopted to address the challenges experienced in Cambodia. INTRODUCTION: The health workforce will be critical to achieving the health-related and wider Sustainable Development Goals in the years up to 2030. BACKGROUND: In 2006, the countries of the Association of Southeast Asian Nations signed a Mutual Recognition Arrangement in relation to nursing services in the region with the main aim of facilitating the mobility of nursing professionals between countries. To ensure the competency of the health workforce and the quality and safety of health services, member states are required to establish an appropriate regulatory framework. METHODS: This is a qualitative descriptive study. Eighteen key informant interviews were conducted in Cambodia in 2018. Walt and Gilson's policy analysis model was applied to organize and synthesize the data. FINDINGS: Major challenges were identified such as conceptual and cultural issues, limited capacity of Cambodian stakeholders and an unstandardized system with limited coordination. DISCUSSION: In Cambodia, the nursing regulatory environment has expanded greatly over the last decade. Strategies adopted were 'political leadership', optimal utilization of 'outsider's capacity', strengthening 'insider's capacity', and 'dedicated consultation and collaboration and consensus building' involving all players. IMPLICATIONS FOR NURSING AND HEALTH POLICIES: Policymakers in similar resource-limited countries could apply and adapt similar strategic efforts when formulating and implementing health policies, legislation and regulations. 'Outsiders', in this case, represented by development partners can play a vital role in the process, but should not be leading the charge. They should be aligned with national priority to support recipient countries. It is imperative for these countries and development partners to invest in increasing the quantity and quality of nursing leaders who can develop and advance regulatory functions.


Assuntos
Política de Saúde , Formulação de Políticas , Camboja , Serviços de Saúde , Humanos , Desenvolvimento Sustentável
4.
Vet J ; 266: 105571, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33323173

RESUMO

Canine transitional cell carcinoma (cTCC) is the most common malignant tumour in the urinary bladder: it is highly invasive and exhibits metastatic characteristics. Inflammation is also strongly related to cTCC. Epithelial tumours often exhibit a mesenchymal cell phenotype during tumour invasion and metastasis owing to epithelial-mesenchymal transition (EMT), which is often induced in chronic inflammation. The aim of this retrospective study was to investigate the expression of epithelial and mesenchymal cell markers in tumour cells and to evaluate its relationship with prognosis of cTCC. In this study, 29 dogs with cTCC who underwent surgical treatment were enrolled. Clinical parameters were reviewed using medical records. Tissue expression of epithelial and mesenchymal markers was evaluated by immunohistochemical analysis. The association between the expression of mesenchymal cell markers and clinical parameters, including prognosis, was statistically examined. In five normal bladder tissues used as controls, no expression of mesenchymal markers was observed, except for one tissue that expressed fibronectin. Conversely, epithelial tumour cells expressed vimentin and fibronectin in 23/29 and 19/28 cTCC tissues, respectively. Regarding clinical parameters, vimentin score in Miniature Dachshunds was significantly higher than those in other dog breeds (P < 0.001). Multivariate survival analyses revealed that age>12 years was related to shorter progression-free survival (P = 0.02). Higher vimentin score, lower fibronectin score, and advanced clinical T stage were significantly correlated with shorter median survival time (P < 0.05). The results of this study indicate that vimentin expression was associated with cTCC progression. Further studies are needed to examine the incidence and relevance of EMT in cTCC.


Assuntos
Carcinoma de Células de Transição/veterinária , Doenças do Cão/patologia , Transição Epitelial-Mesenquimal , Neoplasias da Bexiga Urinária/veterinária , Fatores Etários , Animais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células de Transição/metabolismo , Doenças do Cão/metabolismo , Cães , Feminino , Fibronectinas/metabolismo , Imuno-Histoquímica , Masculino , Prognóstico , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/metabolismo , Vimentina/metabolismo
5.
Clin Radiol ; 74(8): 650.e13-650.e18, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31014571

RESUMO

AIM: To compare perfusion computed tomography (CT) with reconstructed image from source data using low-dose contrast agent and conventional 320-row CT for the evaluation of renal tumours. MATERIALS AND METHODS: Twenty-eight patients underwent conventional CT (C-CT) and 26 patients underwent perfusion CT with low-dose (40 ml) contrast agent. Image noise, arterial visualisation, the sharpness of the corticomedullary junction (CMJ), and overall image quality were each assessed using a four-point scale. The tumour detection rate for lesions <4 cm (n=66) was also evaluated. Quantitative image parameters including image noise and the contrast-to-noise ratios (CNRs) of the renal artery and CMJ were measured. The volume CT dose index (CTDI), dose-length product (DLP), and size-specific dose estimate (SSDE) were also recorded. RESULTS: Although the image noise of perfusion CT was higher than that of C-CT and the overall image quality of perfusion CT was lower than that of C-CT, the arterial visualisation score of perfusion CT was significantly higher than that of C-CT. The CMJ sharpness scores of the two techniques were equivalent. Sensitivity and positive predictive values were also equivalent with respect to tumour detection. The CNRs of both the left and right renal arteries were significantly higher on perfusion CT than on C-CT. The CTDI, DLP, and SSDE of perfusion CT were significantly lower than those of C-CT. CONCLUSION: Perfusion CT using low-dose contrast agent preserved arterial visualisation and the tumour detection rate and achieved a low radiation dose despite image quality degradation and image noise.


Assuntos
Meios de Contraste , Neoplasias Renais/diagnóstico por imagem , Doses de Radiação , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Rim/diagnóstico por imagem , Masculino , Imagem de Perfusão/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos
7.
Clin Radiol ; 72(9): 780-785, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28442142

RESUMO

AIMS: To identify predictors of a therapeutic effect after transarterial chemoembolisation using drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Between January 2015 and July 2015, tumour variables and angiographic data were collected for 25 patients (49 target lesions) after they had undergone the DEB-TACE procedure for HCC. The therapeutic effect was evaluated according to the Response Evaluation Criteria in Cancer of the Liver at follow-up dynamic computed tomography (CT) performed within 1-4 months after the procedure. A p<0.05 was considered significant. RESULTS: On a target lesion basis, the objective response (TE3/4) rate was 63.3% (31 of 49). On univariate analysis, larger size (≥2 cm) was a predictor of an objective response (p=0.029). The tumour location of the medial (segment 4) or caudate (segment 1) lobe also indicated a poor therapeutic effect (TE1/2), but not at the level of significance (p=0.051). Multivariate analysis identified tumour size (odds ratio, 8.60; 95% confidence interval, 1.87-62.8) and tumour location (odds ratio, 12.2; 95% confidence interval, 2.12-129.8) as significant factors associated with a therapeutic effect. On a patient basis, 10 of 25 (40%) patients showed complete response/partial response. There were no significant differences between complete response/partial response and stable disease/progressive disease regarding age, gender, tumour markers, history of previous treatment, Child-Pugh class, T-stage, or Barcelona Clinic Liver Cancer Staging. CONCLUSION: A short-term therapeutic effect was associated with tumour size and location on a target lesion basis.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/métodos , Epirubicina/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Microesferas , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
Vet J ; 221: 38-47, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28283079

RESUMO

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested as effective adjunctive anti-tumour agents in human and veterinary medicine. However, the molecular mechanisms associated with their anti-tumour effects and correlations with the expression of cyclooxygenase (COX) and related molecules in tumours remain controversial. The objective of this study was to compare the expression profiles of COX and related molecules with NSAID sensitivity and to explore the molecular mechanisms of anti-tumour effects. The expression profiles of COXs, prostaglandins (PGs), PGD2 synthases, and PGE2 synthases were obtained, and their correlations with in vitro sensitivity to the NSAIDs piroxicam, carprofen, and robenacoxib were examined, using 26 canine cancer cell lines. Subsequently, microarray analysis was performed using one melanoma cell line to gain insight into mechanisms by which NSAIDs could exert cytotoxic effects. No strong correlation was observed between the cellular expression of COX and related molecules and sensitivity to NSAID treatment. Additionally, NSAIDs inhibited cell growth only at considerably higher concentrations than those required for functional COX inhibition. Microarray data demonstrated that five genes (SLC16A6, PER2, SLC9A8, HTR2B, and BRAF) were significantly upregulated and that four genes (LOC488305, H2AFJ, LOC476445, and ANKRD43) were significantly downregulated by NSAID exposure to the melanoma cell line. These results suggest that the direct in vitro anti-tumour effects of NSAIDs might be mediated by COX/PG-independent pathways. Novel candidate genes that could potentially be involved in the anti-tumour effects of NSAIDs were identified. Further validation and elucidation of their associated mechanisms will contribute to patient selection in clinical settings and the development of effective combination therapies.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antineoplásicos/uso terapêutico , Doenças do Cão/tratamento farmacológico , Neoplasias/veterinária , Animais , Carbazóis/uso terapêutico , Linhagem Celular Tumoral , Inibidores de Ciclo-Oxigenase/uso terapêutico , Dinoprostona/metabolismo , Difenilamina/análogos & derivados , Difenilamina/uso terapêutico , Cães , Relação Dose-Resposta a Droga , Perfilação da Expressão Gênica/veterinária , Neoplasias/tratamento farmacológico , Fenilacetatos/uso terapêutico , Piroxicam/uso terapêutico , Prostaglandina D2/metabolismo
9.
J Gastroenterol ; 53(3): 276-300, mar. 2017.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-963634

RESUMO

BACKGROUND: This clinical practice guideline addresses six questions related to liberation from mechanical ventilation in critically ill adults. It is the result of a collaborative effort between the American Thoracic Society (ATS) and the American College of Chest Physicians (CHEST). METHODS: A multidisciplinary panel posed six clinical questions in a population, intervention, comparator, outcomes (PICO) format. A comprehensive literature search and evidence synthesis was performed for each question, which included appraising the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The Evidence-to-Decision framework was applied to each question, requiring the panel to evaluate and weigh the importance of the problem, confidence in the evidence, certainty about how much the public values the main outcomes, magnitude and balance of desirable and undesirable outcomes, resources and costs associated with the intervention, impact on health disparities, and acceptability and feasibility of the intervention. RESULTS: Evidence-based recommendations were formulated and graded initially by subcommittees and then modified following full panel discussions. The recommendations were confirmed by confidential electronic voting; approval required that at least 80% of the panel members agree with the recommendation. CONCLUSIONS: The panel provides recommendations regarding liberation from mechanical ventilation. The details regarding the evidence and rationale for each recommendation are presented in the American Journal of Respiratory and Critical Care Medicine and CHEST


Assuntos
Humanos , Colelitíase/diagnóstico , Colelitíase/terapia , Ácido Ursodesoxicólico , Litotripsia , Esfinterotomia Endoscópica , Colecistectomia Laparoscópica , Coledocolitíase/terapia , Abordagem GRADE
12.
Clin Radiol ; 71(12): 1277-1283, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27210243

RESUMO

AIM: To clarify the frequency of fatty change in moderately and poorly differentiated hepatocellular carcinomas (mHCCs and pHCCs) and its relationship to arterial blood flow. MATERIALS AND METHODS: One hundred and thirty-six surgically resected HCC lesions were studied. All patients had undergone dynamic magnetic resonance imaging (MRI) with chemical-shift-encoded water-fat imaging (CSI). The presence of fat was identified by a signal drop-off on CSI and confirmed at pathology. Lesions were classified into four groups in the arterial phase; G1, hypointense; G2, isointense; G3, slightly and heterogeneously hyperintense; G4, markedly and homogeneously hyperintense. The number of cumulative arteries (CAs) in the tumours in the pathology examination were counted. RESULTS: A fat component was observed significantly more frequently in the pHCCs (13/21; 61.9%) compared to the mHCCs (32/101; 31.7%; p=0.013). The numbers of lesions in each group were as follows: (G1, G2, G3, G4) = (18, 9, 23, 4) in the HCCs with fat; (1, 6, 24, 51) in the HCCs without fat (p<0.001); (5, 5, 18, 4) in the mHCCs with fat; (0, 3, 19, 47) in the mHCCs without fat (p<0.001); (11, 0, 2, 0) in the pHCCs with fat; (0, 2, 3, 3) in the pHCCs without fat (p=0.001). The number of CAs in the fat-containing HCCs (5.5±2.9) was significantly lower than that in the HCCs without fat (10.8±5.3; p<0.001). CONCLUSION: A fat component was more commonly observed in the pHCCs than in the mHCCs. The present results showed a possible mechanism of fatty change in mHCCs and pHCCs in relation to decreased arterial blood supply.


Assuntos
Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/diagnóstico por imagem , Lipídeos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Adulto , Idoso , Idoso de 80 Anos ou mais , Artérias/diagnóstico por imagem , Feminino , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Gravidez , Reprodutibilidade dos Testes , Estudos Retrospectivos
13.
Clin Radiol ; 71(5): 432-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26944697

RESUMO

AIM: To clarify whether the heterogeneity of non-cancerous liver parenchyma (NLP) in the hepatobiliary phase on gadoxetic acid enhanced magnetic resonance imaging (MRI) is correlated with hepatocellular carcinoma (HCC) development. MATERIALS AND METHODS: Institutional review board approval was obtained, and the requirements for informed consent were waived for this retrospective study. The imaging characteristics of 84 patients with chronic liver disease who underwent gadoxetic acid-enhanced 3T MRI between January 2013 and October 2014 were examined retrospectively. For the evaluation of the heterogeneity of the intensity in the hepatobiliary phase, the largest possible region of interest was placed on the NLP, and the skewness and kurtosis were calculated using ImageJ software. Skewness is the degree of asymmetry of a histogram, and kurtosis is a measure of the peak. Based on the median values of kurtosis and skewness, the patients were classified into four categories and the categories were compared between the 49 patients with HCC (HCC group) and the 35 patients without HCC (non-HCC group). RESULTS: Kurtosis was significantly higher in the HCC group compared to the non-HCC group (1.19±1.15 versus 0.43±0.83; p=0.0006). Skewness was significantly lower in the HCC group than in the non-HCC group (1.19±1.15 versus 0.43±0.83; p=0.0152). In a multivariate logistic analysis, the category showing lower-than-the-median (-0.1185) skewness and higher-than-the-median (0.547) kurtosis was significantly and independently associated with HCC development (p=0.0031). CONCLUSION: The heterogeneity of NLP in the hepatobiliary phase on gadoxetic acid enhanced MRI may reflect the development of HCC.


Assuntos
Biomarcadores , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Gadolínio DTPA , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
14.
Int J Lab Hematol ; 38(1): 27-33, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26333345

RESUMO

INTRODUCTION: Pentra MS CRP is an automated hematology analyzer capable of cytochemistry using Chlorazol black E, a lipid-staining agent, for white blood cell (WBC) differentials. Pentra MS CRP displays a WBC scattergram according to the cell volume obtained using flow impedance and light absorbance reflecting the Chlorazol black E (CBE)-positive lipid content. METHOD: Neutrophil scattergrams obtained using Pentra MS CRP were compared between 5 patients with myelodysplastic syndrome (MDS) and normal controls. Sudan black B (SBB)-staining patterns of peripheral blood neutrophils were subdivided into four types (types I, II, III, and VI) based on their staining intensity and scored by counting 200 cells. Such SBB scores were also compared between the two groups. RESULTS: Neutrophil scattergrams deviated downward in the MDS group, suggesting the decreased CBE positivity that seemed reflect the reduction of the lipid content in dysplastic neutrophils. SBB scores determined in this study were also decreased in the MDS group when compared with those in normal controls. CONCLUSION: Pentra MS CRP might rapidly generate useful information on dysplastic neutrophils in patients with MDS based on its cytochemistry for WBC differentials during routine laboratory hematology.


Assuntos
Granulócitos/patologia , Contagem de Leucócitos/métodos , Síndromes Mielodisplásicas/diagnóstico , Mielopoese , Neutrófilos/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Granulócitos/metabolismo , Humanos , Contagem de Leucócitos/instrumentação , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo
15.
J Phys Condens Matter ; 27(30): 305301, 2015 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-26173149

RESUMO

A systematic study of simulated atomic-resolution electronic energy-loss spectroscopy (EELS) for different graphene nanoribbons (GNRs) is presented. The results of ab initio studies of carbon [Formula: see text] core-loss EELS on GNRs with different ribbon edge structures and different hydrogen terminations show that theoretical core-loss EELS can distinguish key structural features at the atomic scale. In addition, the combination of polarized core-loss EELS with symmetry resolved electronic partial density of states calculations can be used to identify the origins of all the primary features in the spectra. For example, the nature of the GNR edge structure (armchair, zigzag, etc) can be identified, along with the degree of hydrogenation. Hence it is possible to use the combination of ab initio calculations with high resolution, high energy transmission core-loss EELS experiments to determine the local atomic arrangement and chemical bonding states (i.e. a structural fingerprint) in GNRs, which is essential for future practical applications of graphene.

16.
Vet J ; 205(2): 288-96, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25975851

RESUMO

Metastases are associated with a poor prognosis for canine mammary gland tumours (CMGTs). Metastatic and non-metastatic clones were isolated previously from a single malignant CMGT cell line. The difference in metastatic potential between the two cell lines was hypothesised to be associated with distinct cellular signalling. The aim of this study was to screen for compounds that specifically target metastatic cells in order to improve CMGT therapeutic outcomes. The two clonal cell lines were characterised by transcriptome analysis and their sensitivity to a library of 291 different compounds was compared. The metastatic clone exhibited elevated expression of molecules associated with degradation of the extracellular matrix, epithelial-mesenchymal transition and cancer stem cell phenotype. This was confirmed using a matrigel invasion assay and by assessment of aldehyde dehydrogenase activity. The mitochondrial respiratory chain complex inhibitors (MRCIs; rotenone, antimycin and oligomycin) significantly inhibited the growth of the metastatic clone. Although MRCIs similarly depleted mitochondrial ATP in both clones, the subsequent cellular response was different, with toxicity to the metastatic clone being independent of AMP-activated protein kinase activity. The results of this study suggest a potential utility of MRCIs as anti-tumour agents against metastatic CMGTs. Further studies are needed to investigate the clinical utility of MRCIs and to determine the association between MRCI sensitivity and malignancy.


Assuntos
Antineoplásicos/farmacologia , Doenças do Cão/tratamento farmacológico , Neoplasias Mamárias Animais/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Células Clonais , Cães , Feminino , Regulação Neoplásica da Expressão Gênica , Transcriptoma
17.
Vet J ; 205(2): 297-304, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25981932

RESUMO

Metformin is an oral hypoglycaemic drug used in type 2 diabetes. Its pharmacological activity reportedly involves mitochondrial respiratory complex I, and mitochondrial respiratory complex inhibitors have a strong inhibitory effect on the growth of metastatic canine mammary gland tumour (CMGT) cell lines. It is hypothesised that metformin has selective anti-tumour effects on metastatic CMGT cells. The aim of this study was to investigate the in vitro effect of metformin on cell growth, production of ATP and reactive oxygen species (ROS), and the AMP-activated protein kinase (AMPK) mammalian target of rapamycin (mTOR) pathway in two CMGT clonal cell lines with different metastatic potential. In addition, transcriptome analysis was used to determine cellular processes disrupted by metformin and in vivo anti-tumour effects were examined in a mouse xenograft model. Metformin inhibited CMGT cell growth in vitro, with the metastatic clone (CHMp-5b) displaying greater sensitivity. ATP depletion and ROS elevation were observed to a similar extent in the metastatic and non-metastatic (CHMp-13a) cell lines after metformin exposure. However, subsequent AMPK activation and mTOR pathway inhibition were prominent only in metformin-insensitive non-metastatic cells. Microarray analysis revealed inhibition of cell cycle progression by metformin treatment in CHMp-5b cells, which was further confirmed by Western blotting and cell cycle analysis. Additionally, metformin significantly suppressed tumour growth in xenografted metastatic CMGT cells. In conclusion, metformin exhibited an anti-tumour effect in metastatic CMGT cells through AMPK-independent cell cycle arrest. Its mechanism of action differed in the non-metastatic clone, where AMPK activation and mTOR inhibition were observed.


Assuntos
Doenças do Cão/tratamento farmacológico , Hipoglicemiantes/farmacologia , Neoplasias Mamárias Animais/tratamento farmacológico , Metformina/farmacologia , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cães , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Filamentos Intermediários , Camundongos , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo
18.
Clin Radiol ; 70(3): 254-61, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25522901

RESUMO

AIM: To clarify the detectability of hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI at 3 T with dual-source parallel radiofrequency (RF) excitation. MATERIALS AND METHODS: Twelve patients with 26 HCCs who each underwent multidetector row CT (MDCT), gadoxetic acid-enhanced MRI with dual-source parallel RF excitation, and angiography-assisted CT prior to living related-liver transplantation. Three blinded readers independently reviewed the images obtained by each imaging technique for the presence of HCC on a segment-by-segment basis using a five-point confidence scale. The area under the receiver operating characteristic curve (Az), sensitivity, and specificity were compared among the three techniques. RESULTS: The Az values of gadoxetic acid-enhanced MRI were highest for all readers, although no significant difference in Az value among the three methods was obtained. No significant differences in sensitivity or specificity were observed among the three techniques for each reader. CONCLUSION: Gadoxetic acid-enhanced MRI at 3 T with dual-source parallel RF excitation has relatively high-level diagnostic potential for the detection of HCC in patients with severe liver dysfunction, which was equivalent to that of MDCT and angiography-assisted CT. Dual-source parallel RF excitation would have a clinical impact on 3 T MRI of the liver.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Meios de Contraste , Gadolínio DTPA , Aumento da Imagem/métodos , Neoplasias Hepáticas/diagnóstico , Imageamento por Ressonância Magnética/métodos , Idoso , Angiografia , Carcinoma Hepatocelular/complicações , Diagnóstico Diferencial , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Fígado/patologia , Cirrose Hepática/complicações , Hepatopatias/etiologia , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores/métodos , Variações Dependentes do Observador , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodos
19.
Int J Lab Hematol ; 37(2): 208-16, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24915801

RESUMO

INTRODUCTION: Pentra MS CRP is a new automated hematology analyzer that can rapidly and reliably provide 5-part differential of leukocytes (5-Diff) and C-reactive protein (CRP) within approximately 3.5 min using a small volume of whole blood (35 µL). METHODS: We evaluated the basic performance of Pentra MS CRP and correlations with Sysmex XN-3000, manual microscopic count, and Hitachi LABOSPECT. RESULTS: Pentra MS CRP demonstrated good repeatability and linearity without any significant carryover for all parameters examined (WBC, RBC, HGB, Hct, PLT, 5-Diff, and CRP). Complete blood cell count (CBC) data examined by Pentra MS CRP correlated well with those evaluated by Sysmex XN-3000 (R ≥ 0.9880). Absolute number of NEU, LYM, and EOS also showed the good correlation (R ≥ 0.9866) between the two analyzers. The correlation with the manual microscopic count was within acceptable criteria. Furthermore, when CRP was examined in hemolyzed whole blood by Pentra MS CRP and converted to plasma concentrations according to Hct, it correlated well (R = 0.9964) with serum CRP examined by Hitachi LABOSPECT. CONCLUSION: Pentra MS CRP is a convenient and reliable analyzer especially in the emergency unit of hospitals in which the prompt and simultaneous measurement of CBC including 5-Diff and CRP is often necessary.


Assuntos
Automação , Contagem de Células Sanguíneas/métodos , Proteína C-Reativa , Contagem de Células Sanguíneas/instrumentação , Contagem de Células Sanguíneas/normas , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
Placenta ; 35(12): 974-80, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25465707

RESUMO

INTRODUCTION: Autophagy has not been studied extensively in the human placenta. This study was performed to determine whether autophagy is increased in the placentas of women with hypertensive disorders in pregnancy compared to normotensive pregnancies. METHODS: LC3-II and p62 protein expression were examined by quantitative Western blotting analysis in 40 placentas from women not experiencing labor pains. The 40 placentas were from 13, 8, and 19 women with preeclampsia, gestational hypertension, and normal pregnancy, respectively. Hypertensive disorders in pregnancy included preeclampsia and gestational hypertension. RESULTS: LC3-II expression was significantly increased, while that of p62 was significantly reduced in 21 placentas of women with hypertensive disorders compared to those with normal blood pressure irrespective of the presence or absence of fetal growth restriction (FGR). LC3-II expression was also significantly increased in 13 placentas of women with preeclampsia irrespective of the presence or absence of FGR. DISCUSSION: The results of this study suggested that autophagy is active in the placenta of hypertensive disorders even in the absence of FGR.


Assuntos
Autofagia/fisiologia , Hipertensão Induzida pela Gravidez/metabolismo , Placenta/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Biomarcadores/metabolismo , Feminino , Humanos , Hipertensão Induzida pela Gravidez/patologia , Proteínas Associadas aos Microtúbulos/metabolismo , Placenta/patologia , Gravidez , Proteína Sequestossoma-1
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