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2.
Nat Food ; 4(11): 941-948, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37932438

RESUMO

Several factors have traditionally hampered the effectiveness of agricultural extension services, including limited institutional capacity and reach. Here we assess the potential of large language models (LLMs), specifically Generative Pre-trained Transformer (GPT), to transform agricultural extension. We focus on the ability of LLMs to simplify scientific knowledge and provide personalized, location-specific and data-driven agricultural recommendations. We emphasize shortcomings of this technology, informed by real-life testing of GPT to generate technical advice for Nigerian cassava farmers. To ensure a safe and responsible dissemination of LLM functionality across farming worldwide, we propose an idealized LLM design process with human experts in the loop.


Assuntos
Agricultura , Tecnologia , Humanos , Fazendas , Idioma , Nigéria
3.
Phys Rev Lett ; 129(15): 156401, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36269973

RESUMO

Chiral materials have attracted significant research interests as they exhibit intriguing physical properties, such as chiral optical response, spin-momentum locking, and chiral induced spin selectivity. Recently, layered transition metal dichalcogenide 1T-TaS_{2} has been found to host a chiral charge density wave (CDW) order. Nevertheless, the physical consequences of the chiral order, for example, in electronic structures and the optical properties, are yet to be explored. Here, we report the spectroscopic visualization of an emergent chiral electronic band structure in the CDW phase, characterized by windmill-shaped Fermi surfaces. We uncover a remarkable chirality-dependent circularly polarized Raman response due to the salient in-plane chiral symmetry of CDW, although the ordinary circular dichroism vanishes. Chiral Fermi surfaces and anomalous Raman responses coincide with the CDW transition, proving their lattice origin. Our Letter paves a path to manipulate the chiral electronic and optical properties in two-dimensional materials and explore applications in polarization optics and spintronics.

4.
AJNR Am J Neuroradiol ; 42(10): 1769-1775, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34385143

RESUMO

BACKGROUND AND PURPOSE: The detection of cerebral aneurysms on MRA is a challenging task. Recent studies have used deep learning-based software for automated detection of aneurysms on MRA and have reported high performance. The purpose of this study was to evaluate the incremental value of using deep learning-based software for the detection of aneurysms on MRA by 2 radiologists, a neurosurgeon, and a neurologist. MATERIALS AND METHODS: TOF-MRA examinations of intracranial aneurysms were retrospectively extracted. Four physicians interpreted the MRA blindly. After a washout period, they interpreted MRA again using the software. Sensitivity and specificity per patient, sensitivity per lesion, and the number of false-positives per case were measured. Diagnostic performances, including subgroup analysis of lesions, were compared. Logistic regression with a generalized estimating equation was used. RESULTS: A total of 332 patients were evaluated; 135 patients had positive findings with 169 lesions. With software assistance, patient-based sensitivity was statistically improved after the washout period (73.5% versus 86.5%, P < .001). The neurosurgeon and neurologist showed a significant increase in patient-based sensitivity with software assistance (74.8% versus 85.2%, P = .03, and 56.3% versus 84.4%, P < .001, respectively), while the number of false-positive cases did not increase significantly (23 versus 30, P = .20, and 22 versus 24, P = .75, respectively). CONCLUSIONS: Software-aided reading showed significant incremental value in the sensitivity of clinicians in the detection of aneurysms on MRA without a significant increase in false-positive findings, especially for the neurosurgeon and neurologist. Software-aided reading showed equivocal value for the radiologist.


Assuntos
Aprendizado Profundo , Aneurisma Intracraniano , Encéfalo , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Angiografia por Ressonância Magnética , Estudos Retrospectivos , Sensibilidade e Especificidade , Software
5.
J Eur Acad Dermatol Venereol ; 35 Suppl 1: 5-9, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33619779

RESUMO

Topical therapy is the mainstay of treatment for the majority of patients with psoriasis vulgaris (chronic plaque psoriasis), with combinations of vitamin D analogues and glucocorticoids having been shown to negate many of the negative effects associated with either monocomponent individually. Following the established efficacy of fixed-dose combination calcipotriol (Cal; 50 µg/g) plus betamethasone dipropionate (BD; 0.5 mg/g) ointment and gel formulations, a novel Cal/BD foam formulation was developed. When applied, Cal/BD foam forms a supersaturated solution on the skin, increasing the penetration and bioavailability of Cal and BD. Early data indicate that this results in improved efficacy outcomes versus Cal/BD ointment, without negatively affecting safety outcomes (such as the incidence/severity of side effects or impacted calcium homeostasis or hypothalamic-pituitary-adrenal axis). This article discusses the potency and absorption of fixed-dose combination Cal/BD foam, as well as the positive early efficacy and safety data associated with its utilisation in the treatment of psoriasis vulgaris.


Assuntos
Fármacos Dermatológicos , Psoríase , Betametasona/análogos & derivados , Calcitriol/análogos & derivados , Fármacos Dermatológicos/efeitos adversos , Combinação de Medicamentos , Humanos , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Psoríase/tratamento farmacológico , Resultado do Tratamento
8.
Neoplasma ; 67(5): 992-1001, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32412774

RESUMO

Limitations of the current therapeutic approach have raised the need for a novel therapeutic agent in breast cancer. Recently, interest in drugs targeting the tumor microenvironment (TME) had drawn attention in the treatment of breast cancer. Furthermore, recent studies have suggested the role of adipocytes, which are part of the TME, in tumor initiation, growth, and metastasis. In this study, we investigated the metabolic interaction between adipocytes and breast cancer cells and its potential as a new therapeutic target in breast cancer. Breast cancer cell lines and human breast cancer tissue samples were evaluated. Compared to cancer cells cultured alone, or the control group, those co-cultured with adipocytes showed lipid transfer from adipocytes to cancer cells and it was different according to the molecular subtype of breast cancer. Breast cancer cells affected the lipolysis of adipocytes and adipocytes affected the ß-oxidation of breast cancer cells. The key molecule of the process was fatty acid binding protein 4 (FABP4), which is combined with free fatty acid (FFA) and supports its migration to cancer cells. When FABP4 was suppressed, lipid transfer between adipocytes and cancer cells, lipolysis of adipocytes, and ß-oxidation of breast cancer cells were reduced. Furthermore, the expression of lipid metabolism-related proteins and lipolysis-related proteins in breast cancer with adipose stroma showed significantly different expression according to the region of breast cancer tissue. Taken together, we demonstrated the metabolic interaction between adipocytes and breast cancer cells. Breast cancer cells increase the lipolysis in adipocytes and produce a fatty acid, and fatty acid enters into cancer cells. Also, adipocytes contribute to the survival and growth of cancer cells through increased mitochondrial ß-oxidation by using fatty acid from adipocytes. The key molecule of the process is FABP4 and when FABP4 is suppressed, the metabolic interaction is reduced, suggesting its role as a potential therapeutic target.


Assuntos
Adipócitos/metabolismo , Neoplasias da Mama/metabolismo , Transferência de Energia , Metabolismo dos Lipídeos , Técnicas de Cocultura , Proteínas de Ligação a Ácido Graxo/genética , Feminino , Humanos , Lipólise , Microambiente Tumoral
9.
AJNR Am J Neuroradiol ; 41(5): 889-897, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32381544

RESUMO

BACKGROUND AND PURPOSE: This work investigated alterations in functional connectivity (FC) and associated structures in patients with Angelman syndrome (AS) by using integrated quantitative imaging analysis and connectivity measures. MATERIALS AND METHODS: We obtained 3T brain MR imaging, including resting-state functional MR imaging, diffusion tensor imaging, and 3D T1-weighted imaging from children with AS (n = 14) and age- and sex-matched controls (n = 28). The brains of patients with AS were analyzed by measuring FC, white matter microstructural analysis, cortical thickness, and brain volumes; these were compared with brains of controls. RESULTS: Interregional FC analysis revealed significantly reduced intra- and interhemispheric FC, especially in the basal ganglia and thalamus, in patients with AS. Significant reductions in fractional anisotropy were found in the corpus callosum, cingulum, posterior limb of the internal capsules, and arcuate fasciculus in patients with AS. Quantitative structural analysis also showed gray matter volume loss of the basal ganglia and diffuse WM volume reduction in AS compared with the control group. CONCLUSIONS: This integrated quantitative MR imaging analysis demonstrated poor functional and structural connectivity, as well as brain volume reduction, in children with AS, which may explain the motor and language dysfunction observed in this well-characterized neurobehavioral phenotype.


Assuntos
Síndrome de Angelman/fisiopatologia , Encéfalo/fisiopatologia , Rede Nervosa/fisiopatologia , Adolescente , Síndrome de Angelman/diagnóstico por imagem , Síndrome de Angelman/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Criança , Pré-Escolar , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/patologia , Neuroimagem/métodos
10.
Obes Surg ; 28(7): 2130-2134, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29696574

RESUMO

Bariatric surgery offers a therapeutic alternative with favourable weight management, cardiovascular, metabolic and functional outcomes. Bariatric individuals often have functional impairments pre-operatively that can be addressed to improve post-operative results and eventual functional independence. Multidisciplinary team offers the best approach to address peri-operative needs and sustainable weight loss thereafter. We exemplified the application of cardiac rehabilitation therapeutic model in managing two bariatric clients with specific bariatric-related challenges. Our approach focuses on adaptive physical activity, sustainable lifestyle changes to promote post-operative weight loss through education and problem solving as well as secondary prevention of cardiovascular disease. Putting emphasis on addressing physical and psychosocial barriers towards physical activity alongside nutritional aspects potentially confers sustained if not better outcomes on weight reduction and functional improvement.


Assuntos
Cirurgia Bariátrica , Reabilitação Cardíaca , Doenças Cardiovasculares/prevenção & controle , Pneumonia Associada a Assistência à Saúde/terapia , Limitação da Mobilidade , Obesidade Mórbida/reabilitação , Osteoartrite do Joelho/terapia , Adulto , Cirurgia Bariátrica/reabilitação , Reabilitação Cardíaca/métodos , Reabilitação Cardíaca/normas , Exercício Físico/fisiologia , Feminino , Pneumonia Associada a Assistência à Saúde/complicações , Humanos , Masculino , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Osteoartrite do Joelho/complicações , Medicina de Precisão/normas , Período Pré-Operatório , Prevenção Secundária , Redução de Peso
12.
J Dermatolog Treat ; 29(5): 487-495, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29057684

RESUMO

AIM: The occurrence of mental health comorbidities such as depression, anxiety, and suicidal ideation or behavior is not uncommon in the context of psoriasis. The negative influence of psoriatic disease on a patient's physical and mental well-being, in combination with overlapping pathophysiology, increase the risk for clinically significant psychiatric conditions. These psychiatric conditions, in turn, influence the patient's outlook and potentially, prognosis. Although the healthcare community increasingly recognizes the association of mental health comorbidities with psoriasis, the extent of the correlation is not fully appreciated. To better understand the relationship between mental health comorbidities and psoriasis, including prevalence, risk factors, and response of psychiatric comorbidities to psoriasis treatment, a narrative review of the published literature was conducted. METHODS: Data from epidemiologic, observational, and clinical studies demonstrate a substantially greater mental health comorbidity burden in patients with psoriasis compared with those without psoriasis or patients with other dermatologic conditions. RESULT: The influence of contemporary drug therapies on measures of depression and anxiety are predominantly positive, although further data are needed to better understand the effects of long-term therapy. CONCLUSION: Clinicians should consider the heightened potential for mental health comorbidities when determining an optimal management strategy for their patients with psoriasis.


Assuntos
Transtornos Mentais/epidemiologia , Psoríase/patologia , Ansiedade/complicações , Ansiedade/epidemiologia , Ansiedade/patologia , Depressão/complicações , Depressão/epidemiologia , Depressão/patologia , Fármacos Dermatológicos/uso terapêutico , Humanos , Transtornos Mentais/complicações , Transtornos Mentais/patologia , Prevalência , Psoríase/complicações , Psoríase/tratamento farmacológico , Fatores de Risco , Ideação Suicida
14.
J Geophys Res Atmos ; 123(10): 5560-5587, 2018 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32661496

RESUMO

Analysis of sun photometer measured and satellite retrieved aerosol optical depth (AOD) data has shown that major aerosol pollution events with very high fine mode AOD (>1.0 in mid-visible) in the China/Korea/Japan region are often observed to be associated with significant cloud cover. This makes remote sensing of these events difficult even for high temporal resolution sun photometer measurements. Possible physical mechanisms for these events that have high AOD include a combination of aerosol humidification, cloud processing, and meteorological co-variation with atmospheric stability and convergence. The new development of Aerosol Robotic network (AERONET) Version 3 Level 2 AOD with improved cloud screening algorithms now allow for unprecedented ability to monitor these extreme fine mode pollution events. Further, the Spectral Deconvolution Algorithm (SDA) applied to Level 1 data (L1; no cloud screening) provides an even more comprehensive assessment of fine mode AOD than L2 in current and previous data versions. Studying the 2012 winter-summer period, comparisons of AERONET L1 SDA daily average fine mode AOD data showed that Moderate Resolution Imaging Spectroradiometer (MODIS) satellite remote sensing of AOD often did not retrieve and/or identify some of the highest fine mode AOD events in this region. Also, compared to models that include data assimilation of satellite retrieved AOD, the L1 SDA fine mode AOD was significantly higher in magnitude, particularly for the highest AOD events that were often associated with significant cloudiness.

15.
Curr Neurovasc Res ; 14(4): 306-315, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28982333

RESUMO

BACKGROUND: The regulation of cerebral arterial vasomotor tone involves several mechanisms. The role of sympathetic nerves and the adrenergic neurotransmitter, noradrenaline (NA), has been the subject of debate for decades. Moreover, the specific role of endothelin-1 (ET-1) in cerebral arterial vasoconstriction has not been elucidated to date. In this study, we evaluated the contribution of NA and ET-1 to cerebral artery vasoconstriction. METHODS: Arterial responses of rat middle cerebral arteries, and human pial cerebral arteries to cumulative concentrations of NA and ET-1, and to Electrical Field Stimulation (EFS), were evaluated. To assess the role of NA and ET-1 when EFS was applied, experiments were performed in the presence of adrenergic, neurogenic, and endothelin-1 receptor modulators. RESULTS: We found that vasoconstriction of cerebral arteries following EFS requires the application of exogenous NA, whereas neither EFS nor NA alone induced vasoconstriction. The observed vasoconstriction was abolished by α-adrenoreceptor antagonist, catecholamine-release inhibitor, blockade of the perivascular neurons, and by the endothelin-2 receptor antagonist (BQ123). CONCLUSION: Based on our results, cerebral artery vasoconstriction requires simultaneous neurogenic and adrenergic activation and is ET-1 dependent. We hypothesize that NA modulates the release of ET-1. Upon release, ET-1 binds to the ETA-receptor on smooth muscle cells inducing cerebral artery vasoconstriction.


Assuntos
Artérias Cerebrais/fisiologia , Endotelina-1/farmacologia , Norepinefrina/farmacologia , Receptor Cross-Talk/fisiologia , Receptores de Endotelina/fisiologia , Vasoconstrição/fisiologia , Adulto , Idoso , Animais , Artérias Cerebrais/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Ratos Endogâmicos WKY , Receptor Cross-Talk/efeitos dos fármacos , Receptores de Endotelina/agonistas , Vasoconstrição/efeitos dos fármacos , Adulto Jovem
16.
Skin Therapy Lett ; 22(4): 1-6, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28732152

RESUMO

While there are several commercially available treatment options for psoriasis and psoriatic arthritis, there remains a large number of individuals who are refractory to current modalities. In the recent past, there has been increasing evidence that interleukin (IL)-17 plays a vital role in the pathophysiology of psoriasis. Preclinical, phase II, and phase III studies of secukinumab (Cosentyx®) targeting IL-17 and its receptor have thus far proved to be promising. We reviewed the results of phase II and phase III clinical trials for secukinumab in the treatment of psoriasis and psoriatic arthritis. Only published studies were considered in the present review. We also performed an English language literature search from January 2003 to September 2015 using PubMed with any of the following key words: (secukinumab OR AIN457) AND (psoriasis OR psoriatic arthritis). In our review of the literature, seven phase III and five phase II clinical trials, as well as open-label extension studies with unpublished findings were found. Results from phase III clinical trials indicated secukinumab to be efficacious and safe for the treatment of psoriasis and psoriatic arthritis according to Psoriasis Area and Severity Index (PASI) and American College of Rheumatology (ACR) scores. The safety profile of this agent was similar across all studies, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, headache, and injection site reaction. Secukinumab demonstrates rapid and robust clinical improvement accompanied by a favorable short- term safety profile. The results of the phase III trials continue to reinforce the theory that the IL-17 pathway is an essential target in psoriasis and psoriatic arthritis treatment. Additional extension studies of lower level evidence are needed to further understand the safety profile of the drug.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Interleucina-17/antagonistas & inibidores , Psoríase/tratamento farmacológico , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados , Cefaleia , Humanos
17.
J Eur Acad Dermatol Venereol ; 31(12): 1999-2009, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28681405

RESUMO

Psoriasis can be a socially isolating disease due to debilitating physical symptoms and the stigma patients feel because of the appearance of their skin. Mental health comorbidities such as anxiety, depression and suicidal ideation and behaviour (SIB) are prevalent in patients with psoriasis. Patients with mild psoriasis can experience psychiatric comorbidities; however, disorders such as depression and SIB are more common in patients with severe psoriasis or psoriatic arthritis. Psychiatric disorders can both result from and contribute to progression of psoriasis, suggesting that psoriasis and psychiatric conditions, such as depression, may have overlapping biological mechanisms. Proinflammatory cytokines such as interleukin (IL)-1 and IL-6 are elevated in both psoriasis and depression, indicating that the inflammatory process may be involved in the progression of both diseases. Elevated cytokine levels in the central nervous system cause physiologic and biochemical changes that may contribute to the development of depression. In this review of the literature, we discuss the evidence that supports the association of psoriasis with mental health disorders and the tools used to detect the presence of these comorbidities. Additionally, we review the most prominent hypotheses on the mechanisms by which the inflammatory response and elevated cytokines can cause depression. These results highlight the role that systemic inflammation plays in the various mental health comorbidities associated with psoriasis, including depression and SIB.


Assuntos
Citocinas/fisiologia , Depressão/etiologia , Psoríase/complicações , Ideação Suicida , Suicídio , Humanos , Psoríase/etiologia
18.
AJNR Am J Neuroradiol ; 38(6): 1212-1217, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28385885

RESUMO

BACKGROUND AND PURPOSE: Typewriter tinnitus, a symptom characterized by paroxysmal attacks of staccato sounds, has been thought to be caused by neurovascular compression of the cochlear nerve, but the correlation between radiologic evidence of neurovascular compression of the cochlear nerve and symptom presentation has not been thoroughly investigated. The purpose of this study was to examine whether radiologic evidence of neurovascular compression of the cochlear nerve is pathognomonic in typewriter tinnitus. MATERIALS AND METHODS: Fifteen carbamazepine-responding patients with typewriter tinnitus and 8 control subjects were evaluated with a 3D T2-weighted volume isotropic turbo spin-echo acquisition sequence. Groups 1 (16 symptomatic sides), 2 (14 asymptomatic sides), and 3 (16 control sides) were compared with regard to the anatomic relation between the vascular loop and the internal auditory canal and the presence of neurovascular compression of the cochlear nerve with/without angulation/indentation. RESULTS: The anatomic location of the vascular loop was not significantly different among the 3 groups (all, P > .05). Meanwhile, neurovascular compression of the cochlear nerve on MR imaging was significantly higher in group 1 than in group 3 (P = .032). However, considerable false-positive (no symptoms with neurovascular compression of the cochlear nerve on MR imaging) and false-negative (typewriter tinnitus without demonstrable neurovascular compression of the cochlear nerve) findings were also observed. CONCLUSIONS: Neurovascular compression of the cochlear nerve was more frequently detected on the symptomatic side of patients with typewriter tinnitus compared with the asymptomatic side of these patients or on both sides of control subjects on MR imaging. However, considering false-positive and false-negative findings, meticulous history-taking and the response to the initial carbamazepine trial should be regarded as more reliable diagnostic clues than radiologic evidence of neurovascular compression of the cochlear nerve.


Assuntos
Nervo Coclear/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Síndromes de Compressão Nervosa/diagnóstico por imagem , Síndromes de Compressão Nervosa/diagnóstico , Zumbido/diagnóstico por imagem , Zumbido/diagnóstico , Doenças do Nervo Vestibulococlear/diagnóstico por imagem , Doenças do Nervo Vestibulococlear/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos não Narcóticos/uso terapêutico , Carbamazepina/uso terapêutico , Ângulo Cerebelopontino/diagnóstico por imagem , Meato Acústico Externo/diagnóstico por imagem , Potenciais Evocados Auditivos do Tronco Encefálico , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Síndromes de Compressão Nervosa/complicações , Estudos Retrospectivos , Zumbido/etiologia , Doenças do Nervo Vestibulococlear/complicações
19.
Poult Sci ; 96(8): 2811-2819, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28340058

RESUMO

The overall aim of this research was to develop egg freshness prediction models in terms of selected quality indices. Six experiments (4 constant temperatures and 2 variable temperatures) were carried out on hen eggs for a total period of 10, 21, 26, 13, and 105 d at storage temperatures of 30, 20, 20 to 10, 30 to 10, and 5 and 10°C, to observe trends in the relative weight loss (RWL), Haugh unit (HU), yolk index (YI), albumin index (AI), yolk pH, and albumin pH. The results showed that there was an increasing trend in the RWL and a decreasing trend in the YI, AI, and HU for all temperature conditions. The changes in the yolk and albumin pH were not uniform. The data from the constant temperature conditions were used to determine the coefficients of the egg quality prediction models, which consisted of the primary model controlling the change rate of the quality indicator at a temperature condition in differential equation form, and the secondary model controlling the change rate with temperature, which was in quadratic polynomial form. The models were applied to the data from the fluctuating temperature conditions, and the zeroth, third, and eighth order kinetic models described the stepwise change in the RWL, HU, and YI, respectively. The accuracy and bias factor values for the RWL, HU, and YI were 1.116 and 0.940, 1.028 and 1.001, and 1.038 and 0.966, respectively. It can be concluded that the models can be used to predict egg freshness in terms of the RWL, HU, and YI at any temperature condition with in the range of 5 to 30°C during storage.


Assuntos
Ovos/análise , Qualidade dos Alimentos , Armazenamento de Alimentos , Óvulo/fisiologia , Animais , Galinhas , Modelos Teóricos , Temperatura
20.
Neoplasma ; 64(3): 412-420, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28253728

RESUMO

We aimed to investigate the expression of methylation-related proteins (5-meC and DNMT1) in the metastatic breast cancers of variable sites and its association with clinicopathologic factors. A total of 126 metastatic breast cancers (31 bone metastases, 36 brain metastases, 11 liver metastases, 48 lung metastases) were made into tissue microarray and immunohistochemical staining of ER, PR, HER-2, Ki-67, 5-meC, and DNMT1 were performed. Molecular classification was made on the basis of immunohistochemical staining result of ER, PR, HER-2, Ki-67; luminal A, luminal B, HER-2, triple negative breast cancer (TNBC). Methylation-related proteins were differentially expressed based on the metastatic sites. Tumoral and stromal 5-meC showed the lowest expression in the bone metastasis (P < 0.001), tumoral DNMT1 showed the least expression in bone metastasis and the highest expression in the brain metastasis (P < 0.001). Expression of DNMT1 was correlated with ER negativity (P = 0.004), PR negativity (P = 0.011), HER-2 positivity (P = 0.016), higher Ki-67 labeling indices (P = 0.016), and non-luminal A type (P = 0.017). DNMT1 positivity was associated with shorter overall survival in bone metastasis (P = 0.017) and lung metastasis (P = 0.028) by univariate analysis. In conclusion, methylation-related proteins differentially expressed according to the metastatic sites in metastatic breast cancer. Tumoral and stromal 5-meC showed the lowest expression in the bone metastasis. Tumoral DNMT1 expression was low in bone metastasis and highest in brain metastasis.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA Glicosilases/metabolismo , Metilação de DNA , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/secundário , Feminino , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Receptores de Progesterona
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