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1.
Sci Rep ; 10(1): 8802, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32472055

RESUMO

In the past decade, the high morbidity and mortality of atherosclerotic disease have been prevalent worldwide. High-fat food consumption has been suggested to be an overarching factor for atherosclerosis incidence. This study aims to investigate the effects of kefir peptides on high-fat diet (HFD)-induced atherosclerosis in apolipoprotein E knockout (ApoE-/-) mice. 7-week old male ApoE-/- and normal C57BL/6 mice were randomly divided into five groups (n = 8). Atherosclerotic lesion development in ApoE-/- mice was established after fed the HFD for 12 weeks compared to standard chow diet (SCD)-fed C57BL/6 and ApoE-/- control groups. Kefir peptides oral administration significantly improved atherosclerotic lesion development by protecting against endothelial dysfunction, decreasing oxidative stress, reducing aortic lipid deposition, attenuating macrophage accumulation, and suppressing the inflammatory immune response compared with the HFD/ApoE-/- mock group. Moreover, the high dose of kefir peptides substantially inhibited aortic fibrosis and restored the fibrosis in the aorta root close to that observed in the C57BL/6 normal control group. Our findings show, for the first time, anti-atherosclerotic progression via kefir peptides consumption in HFD-fed ApoE-/- mice. The profitable effects of kefir peptides provide new perspectives for its use as an anti-atherosclerotic agent in the preventive medicine.

2.
BMC Complement Med Ther ; 20(1): 68, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32126993

RESUMO

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and has also been associated with a high degree of malignancy and enhanced metastatic capacity. Curcumin (CUR) is well known for its anti-osteosarcoma activity. However, both demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are natural curcumin analogues/congeners from turmeric whose role in osteosarcoma development remains unknown. METHODS: To evaluate the growth inhibitory effects of CUR, DMC and BDMC on osteosarcoma (HOS and U2OS), breast (MDA-MB-231), and melanoma (A2058) cancer cells, we employed the MTT assay, annexin V-FITC /7-AAD staining, and clonogenic assay. RESULTS: CUR,DMC, and BDMC all decreased the viability of HOS, U2OS, MDA-MB-231, and A2058 cancer cells. Additionally, CUR,DMC, and BDMC induced the apoptosis of HOS cells through activation of Smad 2/3 or repression of Akt signaling pathway. Furthermore, the combination of CUR,DMC, and BDMC synergistically reduced cell viability, colony formation and increased apoptosis than either two or a single agent in HOS cells. CONCLUSIONS: The combination of these three compounds could be used as a novel target for the treatment of osteosarcoma.

3.
J Phys Chem A ; 124(11): 2253-2263, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32096999

RESUMO

The protonation sites of aniline molecule play important roles in its chemical reactions, but the preferred protonation site of gaseous aniline has yet to be determined. In this work, we recorded infrared (IR) absorption spectra of three isomers of protonated aniline, H+C6H5NH2, produced on electron bombardment during matrix deposition at 3.2 K of a mixture of aniline and para-H2. The intensities of IR lines of H+C6H5NH2 decreased during maintenance of the electron-bombarded matrix in darkness because of neutralization with electrons that were slowly released from their trapping sites. The observed lines were classified into three groups according to their behavior upon secondary photolysis with light at 375 and 254 nm and assigned to para-, amino-, and ortho-H+C6H5NH2, the three most stable isomers of protonated aniline, according to comparison of experimental spectra with quantum-chemically predicted spectra of five possible isomers of H+C6H5NH2. The spectra of para- and ortho-H+C6H5NH2 are newly distinguished. The approximate relative abundance of these isomers in solid p-H2 was para:amino:ortho ≈ (1.0 ± 0.1):(1.0 ± 0.6):(0.6 ± 0.1). The possible mechanisms of formation are discussed.

4.
J Biomed Sci ; 26(1): 80, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31630678

RESUMO

Autophagy is a major degradation pathway that utilizes lysosome hydrolases to degrade cellular constituents and is often induced under cellular stress conditions to restore cell homeostasis. Another prime degradation pathway in the cells is ubiquitin-proteasome system (UPS), in which proteins tagged by certain types of polyubiquitin chains are selectively recognized and removed by proteasome. Although the two degradation pathways are operated independently with different sets of players, recent studies have revealed reciprocal cross talks between UPS and autophagy at multiple layers. In this review, we summarize the roles of protein ubiquitination and deubiquitination in controlling the initiation, execution, and termination of bulk autophagy as well as the role of ubiquitination in signaling certain types of selective autophagy. We also highlight how dysregulation of ubiquitin-mediated autophagy pathways is associated with a number of human diseases and the potential of targeting these pathways for disease intervention.


Assuntos
Autofagia/genética , Ubiquitina/metabolismo , Ubiquitinação , Animais , Humanos , Camundongos , Ubiquitinas/metabolismo
5.
Molecules ; 24(18)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31547327

RESUMO

Previous studies have revealed the anti-inflammatory and neuroprotective properties of Hericium erinaceus extracts, including the fact that the active ingredient erinacine C (EC) can induce the synthesis of nerve growth factor. However, there is limited research on the use and mechanisms of action of EC in treating neuroinflammation. Hence, in this study, the inflammatory responses of human BV2 microglial cells induced by LPS were used to establish a model to assess the anti-neuroinflammatory efficacy of EC and to clarify its possible mechanisms of action. The results showed that EC was able to reduce the levels of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) proteins produced by LPS-induced BV2 cells, in addition to inhibiting the expression of NF-κB and phosphorylation of IκBα (p-IκBα) proteins. Moreover, EC was found to inhibit the Kelch-like ECH-associated protein 1 (Keap1) protein, and to enhance the nuclear transcription factor erythroid 2-related factor (Nrf2) and the expression of the heme oxygenase-1 (HO-1) protein. Taken together, these data suggest that the mechanism of action of EC involves the inhibition of IκB, p-IκBα, and iNOS expressions and the activation of the Nrf2/HO-1 pathway.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Diterpenos/farmacologia , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Proteínas de Membrana/metabolismo , Camundongos , Microglia/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
6.
Anal Chem ; 91(19): 12461-12467, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31461623

RESUMO

Molecular recognition (e.g., antigen-antibody, DNA-DNA, and streptavidin-biotin) is a generic, yet highly versatile and powerful strategy employed in enzyme-catalyzed signal amplification process. However, this approach is not applicable to metals, anions, and small reactive species (e.g., O2- and F-), as these molecules are too small to bind effectively to the macromolecules. In this paper, we demonstrate an enzyme-catalyzed signal amplification approach based on the controlled binding between streptavidin and target activated affinity-switchable biotin (ASB) probes, for the detection of O2- and F-, using electrochemical and fluorescent detection techniques. The underlying rationale behind this design is that, while the ASB probe would not bind with the streptavidin-enzyme conjugate due to its low binding affinity with streptavidin, in the presence of the target analyte, the ASB probe on the immobilized surface will be activated to form biotin, which can then bind with the enzyme-tagged streptavidin to initiate signal amplification process. This versatile approach can also be applied in the imaging of endogenously secreted O2- along the plasma membrane of living cells using streptavidin conjugated with multiple fluorescent dye reporters. We believe that this ASB probe strategy will be useful for a wide range of applications, such as in basic biological research and medical diagnoses, where highly specific signal enhancement is required.

7.
Cancers (Basel) ; 11(8)2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31430901

RESUMO

Our previous study demonstrated that administration of NVP-BEZ235 (BEZ235), a dual PI3K/mTOR inhibitor, before radiotherapy (RT) enhanced the radiotherapeutic effect in colorectal cancer (CRC) cells both in vitro and in vivo. Here, we evaluated whether maintenance BEZ235 treatment, after combinatorial BEZ235 + RT therapy, prolonged the antitumor effect in CRC. K-RAS mutant CRC cells (HCT116 and SW480), wild-type CRC cells (HT29), and HCT116 xenograft tumors were separated into the following six study groups: (1) untreated (control); (2) RT alone; (3) BEZ235 alone; (4) RT + BEZ235; (5) maintenance BEZ235 following RT + BEZ235 (RT + BEZ235 + mBEZ235); and (6) maintenance BEZ235 following BEZ235 (BEZ235 + mBEZ235). RT + BEZ235 + mBEZ235 treatment significantly inhibited cell viability and increased apoptosis in three CRC cell lines compared to the other five treatments in vitro. In the HCT116 xenograft tumor model, RT + BEZ235 + mBEZ235 treatment significantly reduced the tumor size when compared to the other five treatments. Furthermore, the expression of mTOR signaling molecules (p-rpS6 and p-eIF4E), DNA double-strand break (DSB) repair-related molecules (p-ATM and p-DNA-PKcs), and angiogenesis-related molecules (VEGF-A and HIF-1α) was significantly downregulated after RT + BEZ235 + mBEZ235 treatment both in vitro and in vivo when compared to the RT + BEZ235, RT, BEZ235, BEZ235 + mBEZ235, and control treatments. Cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP), 53BP1, and γ-H2AX expression in the HCT116 xenograft tissue and three CRC cell lines were significantly upregulated after RT + BEZ235 + mBEZ235 treatment. Maintenance BEZ235 treatment in CRC cells prolonged the inhibition of cell viability, enhancement of apoptosis, attenuation of mTOR signaling, impairment of the DNA-DSB repair mechanism, and downregulation of angiogenesis that occurred due to concurrent BEZ235 and RT treatment.

8.
Sci Rep ; 9(1): 10673, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337842

RESUMO

Our previous studies have shown that autophagy mediates the link between ductular reaction (DR) and liver cirrhosis. Whether the subsequent fibrogenic response is regulated by increased autophagy in DR remains unclear. Here, using both human liver specimens and a rat model of liver cirrhosis induced by 2-acetylaminofluorene (AAF) and carbon tetrachloride (CCL4), we explored the involvement of autophagy in regulating mesenchymal transition of ductular cells. Ductular cells from AAF/CCL4 livers exhibited increased autophagy compared to those of normal livers. These cells showed morphological and functional characteristics of mesenchymal cells. Blocking autophagy using bafilomycin A1 or siRNA targeting ATG7 reduced the expression of mesenchymal markers in these ductular cells from AAF/CCL4 livers, indicating a role for autophagy in regulating the mesenchymal phenotype of ductular cells. Furthermore, we show that the mesenchymal transition in DR requires the activation of transforming growth factor-ß (TGF-ß) signaling in an autophagy-dependent manner. Importantly, in cirrhotic human livers, ductular cells that are positive for LC3B also showed increased expression of TGF-ß and fibroblast-specific protein-1. Our data suggest activation of autophagy in ductular cells, and also demonstrate that it is required for the mesenchymal transition during the DR, processes that are critically involved in the pathogenesis of cirrhosis.

9.
Anticancer Res ; 39(4): 2207-2215, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30952769

RESUMO

BACKGROUND/AIM: The local control and clinical outcome of pediatric patients with high-risk neuroblastoma treated with tomotherapy as part of a modern multimodality paradigm was assessed. PATIENTS AND METHODS: Twenty-four high-risk neuroblastoma patients who received radiotherapy (RT) to the primary site using helical tomotherapy (median 21.6 Gy) were included. Local failure (LF) was correlated with biological and clinical prognostic factors. Event-free survival (EFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. RESULTS: After a median follow-up of 43.5 months, the 3-year cumulative incidence of LF, EFS, and OS were 21.1%, 45.8%, and 62.9%, respectively. Elevated serum lactate dehydrogenase ≥1,500 U/l was associated with worse LF (p=0.02). There was no 3-year LF noted for patients with gross residual disease (GRD) who received more than 21.6 Gy. CONCLUSION: We demonstrated favorable local control of tomotherapy for the treatment of high-risk neuroblastoma. Dose escalation of RT for patients with GRD should be investigated.


Assuntos
Neuroblastoma/terapia , Radioterapia de Intensidade Modulada , Adolescente , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/sangue , Masculino , Neuroblastoma/sangue , Prognóstico , Risco , Resultado do Tratamento
10.
Cell Mol Life Sci ; 76(1): 163-178, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30327840

RESUMO

Low-density lipoprotein receptor-related protein 4 (LRP4) is a multi-functional protein implicated in bone, kidney and neurological diseases including Cenani-Lenz syndactyly (CLS), sclerosteosis, osteoporosis, congenital myasthenic syndrome and myasthenia gravis. Why different LRP4 mutation alleles cause distinct and even contrasting disease phenotypes remain unclear. Herein, we utilized the zebrafish model to search for pathways affected by a deficiency of LRP4. The lrp4 knockdown in zebrafish embryos exhibits cyst formations at fin structures and the caudal vein plexus, malformed pectoral fins, defective bone formation and compromised kidney morphogenesis; which partially phenocopied the human LRP4 mutations and were reminiscent of phenotypes resulting form a perturbed Notch signaling pathway. We discovered that the Lrp4-deficient zebrafish manifested increased Notch outputs in addition to enhanced Wnt signaling, with the expression of Notch ligand jagged1b being significantly elevated at the fin structures. To examine conservatism of signaling mechanisms, the effect of LRP4 missense mutations and siRNA knockdowns, including a novel missense mutation c.1117C > T (p.R373W) of LRP4, were tested in mammalian kidney and osteoblast cells. The results showed that LRP4 suppressed both Wnt/ß-Catenin and Notch signaling pathways, and these activities were perturbed either by LRP4 missense mutations or by a knockdown of LRP4. Our finding underscore that LRP4 is required for limiting Jagged-Notch signaling throughout the fin/limb and kidney development, whose perturbation representing a novel mechanism for LRP4-related diseases. Moreover, our study reveals an evolutionarily conserved relationship between LRP4 and Jagged-Notch signaling, which may shed light on how the Notch signaling is fine-tuned during fin/limb development.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Proteínas Relacionadas a Receptor de LDL/genética , Receptores Notch/metabolismo , Proteínas Serrate-Jagged/metabolismo , Transdução de Sinais , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Nadadeiras de Animais/embriologia , Nadadeiras de Animais/metabolismo , Animais , Extremidades/embriologia , Extremidades/fisiologia , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Rim/embriologia , Rim/metabolismo , Proteínas Relacionadas a Receptor de LDL/metabolismo , Mutação , Mutação de Sentido Incorreto , Organogênese , Via de Sinalização Wnt , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
12.
J Microbiol Immunol Infect ; 52(2): 265-272, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28882582

RESUMO

BACKGROUND: Group B Streptococcus (GBS) infection is one of the major causes of neonatal morbidity and mortality. Universal GBS screening with intrapartum antibiotic prophylaxis (IAP) in pregnant women were initiated in 2012 in Taiwan. This study aimed to analyze the most recent maternal GBS colonization rate and the changes in neonatal GBS infection rate from 2011 to 2016. METHODS: All pregnant women and their live born neonates between January 2011 and June 2016 were retrospectively reviewed. Whether GBS screening was done, screening results, presence of risk factors, the use of antibiotics, and neonatal outcome were analyzed. In addition, hospitalized neonates diagnosed with GBS infections were retrieved for comparison of early onset disease (EOD) (<7 days) and late onset disease (LOD) (≥7 days). RESULTS: A total of 9535 women delivered babies during the study period. The maternal GBS screening rate was 71.0% and the colonization rate was 22.6%. The overall neonatal invasive GBS infection rate was 0.81 per 1000 live births and the vertical transmission rate was 1.2%. After 2012, the invasive neonatal GBS infection rate declined from 1.1-1.6‰ to 0.6-0.7‰ in 2014 and thereafter, the GBS EOD incidence rate declined from 2.8‰ to 0.0-0.6‰, but the LOD incidence rate remained approximately 0.7‰. Infants with EOD had strong association with obstetric risk factors. CONCLUSIONS: Taiwan's universal GBS screening with IAP program reduced the incidence rate of neonatal GBS EOD to be lower than 1‰ after 2012. Pediatricians still should pay attention to infants with GBS LOD since its incidence rate remained unchanged.


Assuntos
Complicações Infecciosas na Gravidez/epidemiologia , Infecções Estreptocócicas/epidemiologia , Streptococcus agalactiae/isolamento & purificação , Streptococcus agalactiae/patogenicidade , Adulto , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Masculino , Programas de Rastreamento , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/etiologia , Estudos Retrospectivos , Fatores de Risco , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/etiologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/prevenção & controle , Taiwan/epidemiologia , Resultado do Tratamento
13.
Dent J (Basel) ; 6(4)2018 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-30544680

RESUMO

Phosphophoryn (PP) and dentin sialoprotein (DSP) are two of the most abundant dentin matrix non-collagenous proteins, and are derived from dentin sialoprotein-phosphophoryn (DSP-PP) mRNA. Mutations in the DSP-PP gene are linked to dentinogenesis imperfecta II and III. Previously, we reported transient DSP-PP expression in preameloblast cells first, followed by co-expression in preameloblasts and young odontoblasts, and finally sustained expression in odontoblasts. This phenomenon raised the possibility that DSP/PP proteins secreted by preameloblasts might promote dental pulp cell migration toward the dental pulp border and promote dental pulp cell differentiation. To examine the effects of DSP/PP proteins on dental pulp cell development, we investigated:(1) native PP effects on dental pulpcell migration and matrix protein expression; and (2) recombinant DSP/PP protein effects on cell proliferation and differentiation. We found that PP promoted cell migration and the expression of high levels of Col type I and PP in dental pulp cells. The addition of recombinant DSP/PP proteins affected cell proliferation and differentiation in a dental pulp cell line. These findings strongly suggest that DSP/PP may modulate cell migration, cell proliferation and differentiation, thus leading to dentin formation. DSP/PP protein may be useful clinically for pulp tissue regeneration.

14.
Clin Breast Cancer ; 18(6): 441-450.e2, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29709458

RESUMO

PURPOSE: To identify whether a certain group of breast ductal carcinoma-in-situ (DCIS) patients can be treated with breast-conserving surgery (BCS) alone; to analyze the clinicopathologic features of DCIS and tamoxifen administration in patients treated with BCS who developed ipsilateral breast tumor recurrence (IBTR). PATIENTS AND METHODS: Data for 375 women with breast DCIS who underwent BCS at our institute between June 2003 and October 2010 were analyzed. The patients were divided into different categories according to the recurrence risk predicted using the California/Van Nuys Prognostic Index (USC/VNPI) score (4-6, 7-9, and 10-12), Eastern Cooperative Oncology Group (ECOG) E5194 criteria, or combined risk features with USC/VNPI score and ECOG E5194 criteria. The IBTR and disease-free survival (DFS) rates were calculated by the Kaplan-Meier method. The prognostic effects of age, tumor size, tumor grade, margin width, estrogen receptor status, USC/VNPI score, low-risk characteristics, and tamoxifen use were evaluated by log-rank tests. RESULTS: Of the patients, 168 were treated with breast irradiation after BCS and 207 were not. The patients who were treated with radiotherapy (RT) tended to be younger (< 40 years), to have higher USC/VNPI scores (7-9), and to meet the ECOG E5194 non-cohort 1 criteria. The 7-year risk of IBTR was 6.2% (n = 11) in the patients who received irradiation and 9.0% (n = 22) in those who did not. DFS rates were better in the patients who underwent RT than in those who did not (93.3% vs. 88.5%, P = .056). Among the patients who underwent BCS alone, age ≥ 40 years, margin width > 10 mm, USC/VNPI scores 4-6, ECOG E5194 cohort 1 criteria, estrogen receptor-positive status, and tamoxifen use predicted lower IBTR and better DFS rates. In the multivariate analysis, combined low-risk characteristics (USC/VNPI scores 4-6 and meeting the ECOG E5194 cohort 1 criteria) were identified as an independent prognostic factor of lower IBTR (P = .028) and better DFS (P = .005). CONCLUSION: RT reduces the risk of IBTR after BCS for DCIS of the breast. Patients with combined low-risk characteristics (USC/VNPI scores 4-6 and meeting the ECOG E5194 cohort 1 criteria) may be adequately treated with BCS alone.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Mastectomia Segmentar , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Carcinoma Intraductal não Infiltrante/terapia , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Prognóstico , Radioterapia Adjuvante , Taiwan/epidemiologia , Tamoxifeno/uso terapêutico , Adulto Jovem
15.
J Neurooncol ; 138(3): 637-647, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29557535

RESUMO

INTRODUCTION: Whole brain (WB) re-irradiation for breast cancer patients with progressive brain metastasis after first-course WB radiotherapy (WBRT) is controversial. In this study, we sought to investigate the association between the molecular sub-classifications and breast-specific Graded Prognostic Assessment (GPA, which includes the Karnofsky performance status, molecular subtypes, and age as its indices) and the outcomes of breast cancer patients who received WB re-irradiation. METHODS: Twenty-three breast cancer patients who received WB re-irradiation for relapsed and progressive intracranial lesions after first-course WBRT between 2004 and 2016 were retrospectively reviewed. Patients were divided according to the 4 molecular subtypes of luminal A/B (hormone receptor [HR]+/human epidermal growth factor receptor 2 [HER2]-), luminal HER2 (HR+/HER2+), HER2 (HR-/HER2+), and triple negative (HR-/HER2-). The clinical and radiological responses and survival rates after WB re-irradiation were analyzed. RESULTS: At 1 month after WB re-irradiation, 13 of 23 patients (56.5%) exhibited disappearance or alleviation of neurological symptoms. The median survival time after WB re-irradiation was 2.93 months (95% confidence interval [CI], 1.79-4.08). After WB re-irradiation, patients with HER2-negative tumors had poorer median survival times than those with HER2-positive tumors (2.23 vs. 3.0 months, respectively; p = 0.022). Furthermore, patients with high breast GPA scores (2.5-4.0, n = 11) had longer median survivals than those with low-scores (0-2.0, n = 12) after WB re-irradiation (4.37 vs. 1.57 months, respectively; p < 0.005). CONCLUSIONS: WB re-irradiation may be a feasible treatment option for certain breast cancer patients who develop brain metastatic lesions after first-course WBRT when these lesions are ineligible for radiosurgery or surgery.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/radioterapia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Irradiação Craniana , Reirradiação , Adulto , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/mortalidade , Neoplasias da Mama/mortalidade , Neoplasias da Mama/radioterapia , Irradiação Craniana/efeitos adversos , Progressão da Doença , Humanos , Pessoa de Meia-Idade , Prognóstico , Reirradiação/efeitos adversos , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Transcrição/metabolismo
16.
Int J Surg Pathol ; 26(5): 410-416, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29466906

RESUMO

OBJECTIVE: Diagnosing melanocytic lesions is among the most challenging problems in the practice of pathology. The difficulty of physically masking melanin pigment and the similarity of its color to commonly used chromogens often complicate examination of the cytomorphology and immunohistochemical staining results for tumor cells. Melanin bleach can be very helpful for histopathological diagnosis of heavily pigmented melanocytic lesions. Although various depigmentation methods have been reported, no standardized methods have been developed. This study developed a fully automated platform that incorporates hydrogen peroxide-based melanin depigmentation in an automated immunohistochemical analysis. METHODS AND MATERIALS: The utility of the method was tested in 1 cell block of malignant melanoma cells in pleural effusion, 10 ocular melanoma tissue samples, and 10 cutaneous melanoma tissue samples. Our results demonstrated that the proposed method, which can be performed in only 3 hours, effectively preserves cell cytomorphology and immunoreactivity. RESULTS: The method is particularly effective for removing melanin pigment to facilitate histopathological examination of cytomorphology and for obtaining an unmasked tissue section for immunohistochemical analysis.


Assuntos
Automação Laboratorial/métodos , Imuno-Histoquímica/métodos , Melaninas/química , Melanócitos/patologia , Melanoma/patologia , Clareadores/química , Neoplasias Oculares/patologia , Humanos , Peróxido de Hidrogênio/química , Melaninas/análise , Melanoma/diagnóstico , Melanoma/secundário , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/patologia , Neoplasias Cutâneas/patologia , Fatores de Tempo
17.
Ear Hear ; 39(4): 795-809, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29360687

RESUMO

OBJECTIVE: We investigate the clinical effectiveness of a novel deep learning-based noise reduction (NR) approach under noisy conditions with challenging noise types at low signal to noise ratio (SNR) levels for Mandarin-speaking cochlear implant (CI) recipients. DESIGN: The deep learning-based NR approach used in this study consists of two modules: noise classifier (NC) and deep denoising autoencoder (DDAE), thus termed (NC + DDAE). In a series of comprehensive experiments, we conduct qualitative and quantitative analyses on the NC module and the overall NC + DDAE approach. Moreover, we evaluate the speech recognition performance of the NC + DDAE NR and classical single-microphone NR approaches for Mandarin-speaking CI recipients under different noisy conditions. The testing set contains Mandarin sentences corrupted by two types of maskers, two-talker babble noise, and a construction jackhammer noise, at 0 and 5 dB SNR levels. Two conventional NR techniques and the proposed deep learning-based approach are used to process the noisy utterances. We qualitatively compare the NR approaches by the amplitude envelope and spectrogram plots of the processed utterances. Quantitative objective measures include (1) normalized covariance measure to test the intelligibility of the utterances processed by each of the NR approaches; and (2) speech recognition tests conducted by nine Mandarin-speaking CI recipients. These nine CI recipients use their own clinical speech processors during testing. RESULTS: The experimental results of objective evaluation and listening test indicate that under challenging listening conditions, the proposed NC + DDAE NR approach yields higher intelligibility scores than the two compared classical NR techniques, under both matched and mismatched training-testing conditions. CONCLUSIONS: When compared to the two well-known conventional NR techniques under challenging listening condition, the proposed NC + DDAE NR approach has superior noise suppression capabilities and gives less distortion for the key speech envelope information, thus, improving speech recognition more effectively for Mandarin CI recipients. The results suggest that the proposed deep learning-based NR approach can potentially be integrated into existing CI signal processors to overcome the degradation of speech perception caused by noise.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez/reabilitação , Aprendizado Profundo , Ruído , Percepção da Fala , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão Sinal-Ruído , Adulto Jovem
18.
Curr Top Med Chem ; 17(21): 2370-2380, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28355999

RESUMO

G Protein-Coupled Receptors (GPCRs) are the most common therapeutic targets for drug discovery by the pharmaceutical industries. Since 2007, several three-dimensional X-ray crystallographic structures of ligand-activated GPCRs have been determined in their agonist-bound or inverse agonist-bound states, providing a wealth of fundamental resources for the investigation of the atomic-level mechanism of receptor activation and deactivation. A number of computational methods, such as conventional and enhanced sampling Molecular Dynamic (MD) simulations have been applied to investigate the receptor dynamics bound with ligands of different functional types (i.e., agonist and inverse agonist). In this article, we reviewed recent efforts in characterizing the dynamical activation and deactivation mechanisms of GPCRs induced by different functional types of ligands.


Assuntos
Ligantes , Simulação de Dinâmica Molecular , Receptores Acoplados a Proteínas-G/metabolismo , Humanos , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Receptores Acoplados a Proteínas-G/genética
19.
IEEE Trans Biomed Eng ; 64(2): 372-380, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28113191

RESUMO

OBJECTIVE: This study focuses on the first (S1) and second (S2) heart sound recognition based only on acoustic characteristics; the assumptions of the individual durations of S1 and S2 and time intervals of S1-S2 and S2-S1 are not involved in the recognition process. The main objective is to investigate whether reliable S1 and S2 recognition performance can still be attained under situations where the duration and interval information might not be accessible. METHODS: A deep neural network (DNN) method is proposed for recognizing S1 and S2 heart sounds. In the proposed method, heart sound signals are first converted into a sequence of Mel-frequency cepstral coefficients (MFCCs). The K-means algorithm is applied to cluster MFCC features into two groups to refine their representation and discriminative capability. The refined features are then fed to a DNN classifier to perform S1 and S2 recognition. We conducted experiments using actual heart sound signals recorded using an electronic stethoscope. Precision, recall, F-measure, and accuracy are used as the evaluation metrics. RESULTS: The proposed DNN-based method can achieve high precision, recall, and F-measure scores with more than 91% accuracy rate. CONCLUSION: The DNN classifier provides higher evaluation scores compared with other well-known pattern classification methods. SIGNIFICANCE: The proposed DNN-based method can achieve reliable S1 and S2 recognition performance based on acoustic characteristics without using an ECG reference or incorporating the assumptions of the individual durations of S1 and S2 and time intervals of S1-S2 and S2-S1.


Assuntos
Auscultação Cardíaca/classificação , Auscultação Cardíaca/métodos , Ruídos Cardíacos/fisiologia , Redes Neurais de Computação , Processamento de Sinais Assistido por Computador , Feminino , Humanos , Masculino , Estetoscópios
20.
Oncotarget ; 8(5): 7921-7934, 2017 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-27974702

RESUMO

In addition to clinical factors (tumor and node stage) and treatment factors (equivalent radiotherapy dose and chemotherapy regimen), we assessed whether different performances of various tumor volume measurements help predict the pathological complete response (pCR) of locally advanced rectal cancer (LARC) after preoperative concurrent chemoradiotherapy (CCRT). A total of 122 patients with LARC treated with a long course of CCRT, between December 2009 and March 2015, were enrolled in this bi-institutional study. Tumor delineation was based on standard T2-weighted magnetic resonance imaging or contrast-enhanced computed tomography before CCRT. Tumor compactness was defined as the ratio of the volume and the surface area. The tumor compactness-corrected TV (TCTV) was defined as the ratio of the real TV (RTV) and tumor compactness. Twenty-three (18.9%) patients had a pCR. Areas under the curve of the receiver operating characteristic for pCR prediction calculated using the RTV, cylindrical approximated TV (CATV), and TCTV were 0.724, 0.747, and 0.780, respectively. The prediction performance of TCTV was significantly more efficient than that of both RTV (P = 0.0057) and CATV (P = 0.0329). Multivariate logistic regression analysis revealed tumor compactness (P = 0.001), RTV (P = 0.042), and preoperative clinical nodal status (P = 0.044) as significant predictors of a pCR. In addition, poor tumor compactness was closely associated with lymphovascular space invasion (P = 0.008) and pathological nodal status (P = 0.003). For patients with LARC receiving preoperative CCRT, tumor compactness is a useful radiomic parameter for improving the volumetric based prediction model.


Assuntos
Quimiorradioterapia Adjuvante , Procedimentos Cirúrgicos do Sistema Digestório , Imagem por Ressonância Magnética , Terapia Neoadjuvante , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Tomografia Computadorizada por Raios X , Carga Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Variações Dependentes do Observador , Valor Preditivo dos Testes , Curva ROC , Neoplasias Retais/patologia , Fatores de Risco , Taiwan , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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