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1.
Sci Rep ; 14(1): 13950, 2024 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886395

RESUMO

Tumor-to-normal ratio (T/N) measurement of 18F-FBPA is crucial for patient eligibility to receive boron neutron capture therapy. This study aims to compare the difference in standard uptake value ratios on brain tumors and normal brains using PET/MR ZTE and atlas-based attenuation correction with the current standard PET/CT attenuation correction. Regarding the normal brain uptake, the difference was not significant between PET/CT and PET/MR attenuation correction methods. The T/N ratio of PET/CT-AC, PET/MR ZTE-AC and PET/MR AB-AC were 2.34 ± 0.95, 2.29 ± 0.88, and 2.19 ± 0.80, respectively. The T/N ratio comparison showed no significance using PET/CT-AC and PET/MR ZTE-AC. As for the PET/MRI AB-AC, significantly lower T/N ratio was observed (- 5.18 ± 9.52%; p < 0.05). The T/N difference between ZTE-AC and AB-AC was also significant (4.71 ± 5.80%; p < 0.01). Our findings suggested PET/MRI imaging using ZTE-AC provided superior quantification on 18F-FBPA-PET compared to atlas-based AC. Using ZTE-AC on 18F-FBPA-PET /MRI might be crucial for BNCT pre-treatment planning.


Assuntos
Terapia por Captura de Nêutron de Boro , Neoplasias Encefálicas , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Terapia por Captura de Nêutron de Boro/métodos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/diagnóstico por imagem , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Radioisótopos de Flúor , Compostos de Boro , Fenilalanina/análogos & derivados
2.
Appl Radiat Isot ; 163: 109219, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32561058

RESUMO

One of the eligible criteria for patients to receive boron neutron capture therapy (BNCT) is based on the tumour-to-normal ratio (T/N) measured by FBPA-PET. However, there is no standard protocol for normal region-of-interested delineation. With comparison of contralateral cerebrum, our study revealed the consistency (p < 0.05) and high feasibility using the cerebellum as an alternative normal tissue baseline because of its homogeneous uptake. Following RECIST version 1.1, the standard-operating-procedure (SOP) for the BNCT fulfilled the expected tumour response and tumour shrinkage rate (p < 0.05). Our modified procedure can provide more precise information for BNCT within a reasonable time.


Assuntos
Compostos de Boro/administração & dosagem , Terapia por Captura de Nêutron de Boro/métodos , Neoplasias Encefálicas/radioterapia , Fenilalanina/análogos & derivados , Tomografia por Emissão de Pósitrons/métodos , Estudos de Viabilidade , Humanos , Fenilalanina/administração & dosagem
3.
J Cell Mol Med ; 19(4): 744-59, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25639359

RESUMO

Mitochondria are key organelles in mammary cells in responsible for a number of cellular functions including cell survival and energy metabolism. Moreover, mitochondria are one of the major targets under doxorubicin treatment. In this study, low-abundant mitochondrial proteins were enriched for proteomic analysis with the state-of-the-art two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assistant laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) strategy to compare and identify the mitochondrial protein profiling changes in response to the development of doxorubicin resistance in human uterine cancer cells. The mitochondrial proteomic results demonstrate more than fifteen hundred protein features were resolved from the equal amount pooled of three purified mitochondrial proteins and 101 differentially expressed spots were identified. In which, 39 out of these 101 identified proteins belong to mitochondrial proteins. Mitochondrial proteins such as acetyl-CoA acetyltransferase (ACAT1) and malate dehydrogenase (MDH2) have not been reported with the roles on the formation of doxorubicin resistance in our knowledge. Further studies have used RNA interference and cell viability analysis to evidence the essential roles of ACAT1 and MDH2 on their potency in the formation of doxorubicin resistance through increased cell viability and decreased cell apoptosis during doxorubicin treatment. To sum up, our current mitochondrial proteomic approaches allowed us to identify numerous proteins, including ACAT1 and MDH2, involved in various drug-resistance-forming mechanisms. Our results provide potential diagnostic markers and therapeutic candidates for the treatment of doxorubicin-resistant uterine cancer.


Assuntos
Acetil-CoA C-Acetiltransferase/metabolismo , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Malato Desidrogenase/metabolismo , Proteínas Mitocondriais/metabolismo , Proteoma/metabolismo , Acetil-CoA C-Acetiltransferase/genética , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Eletroforese em Gel Bidimensional , Feminino , Humanos , Immunoblotting , Malato Desidrogenase/genética , Proteínas Mitocondriais/genética , Proteoma/genética , Proteômica/métodos , Interferência de RNA , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologia
4.
Pharmacol Res ; 90: 1-17, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25242635

RESUMO

Drug resistance is a frequent cause of failure in cancer chemotherapy treatments. In this study, a pair of uterine sarcoma cancer lines, MES-SA, and doxorubicin-resistant partners, MES-SA/DxR-2µM cells and MES-SA/DxR-8µM cells, as a model system to investigate resistance-dependent proteome alterations and to identify potential therapeutic targets. We used two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to perform this research and the results revealed that doxorubicin-resistance altered the expression of 208 proteins in which 129 identified proteins showed dose-dependent manners in response to the levels of resistance. Further studies have used RNA interference, H2A.X phosphorylation assay, cell viability analysis, and analysis of apoptosis against reticulocalbin-1 (RCN1) proteins, to prove its potency on the formation of doxorubicin resistance as well as the attenuation of doxorubicin-associated DNA double strand breakage. To sum up, our results provide useful diagnostic markers and therapeutic candidates such as RCN1 for the treatment of doxorubicin-resistant uterine cancer.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Proteínas de Ligação ao Cálcio/metabolismo , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Neoplasias Uterinas/metabolismo , Apoptose/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/genética , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Eletroforese em Gel Bidimensional , Feminino , Humanos , Proteoma , RNA Interferente Pequeno/administração & dosagem , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Regulação para Cima/efeitos dos fármacos
5.
Toxicol Sci ; 139(2): 396-406, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24675091

RESUMO

The nucleus is a key organelle in mammary cells, which is responsible for several cellular functions including cell proliferation, gene expression, and cell survival. In addition, the nucleus is the primary targets of doxorubicin treatment. In the current study, low-abundance nuclear proteins were enriched for proteomic analysis by using a state-of-the-art two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) strategy to compare and identify the nuclear protein profiling changes responsible for the development of doxorubicin resistance in human uterine cancer cells. The results of the nuclear proteomic analysis indicated that more than 2100 protein features were resolved from an equal pooled amount of three purified nuclear proteins and 117 differentially expressed spots were identified. Of these 117 identified proteins, 48 belonged to nuclear proteins and a positive correlation was observed between the expression levels of 32 of these nuclear proteins and an increase in drug resistance. According to our review of relevant research, nuclear proteins such as DNA repair protein XRCC3 (XRCC3) have not been reported to play roles in the formation of doxorubicin resistance. Previous studies have used RNA interference and cell viability analysis to evidence the essential roles of XRCC3 on its potency in the formation of doxorubicin resistance. To sum up, our nuclear proteomic approaches enabled us to identify numerous proteins, including XRCC3, involved in various drug-resistance-forming mechanisms. Our results provide potential diagnostic markers and therapeutic candidates for treating doxorubicin-resistant uterine cancer.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Proteínas de Ligação a DNA/antagonistas & inibidores , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Proteínas Nucleares/metabolismo , Proteômica , Neoplasias Uterinas/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Análise Serial de Proteínas , RNA Interferente Pequeno/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Transfecção , Eletroforese em Gel Diferencial Bidimensional , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia
6.
Electrophoresis ; 34(24): 3305-14, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24115172

RESUMO

Glutathione reductase (GR), a cytosolic protein, plays a vital role in maintaining a correct redox status in cells. However, comprehensive investigations of GR-modulated cellular responses, including protein level alteration and redox regulation, have yet to be performed. In this study, we cultured a human lung adenocarcinoma line transfected with empty pLKO.1 vector as a control, CL1-0shControl, and its GR-knockdown derivative, CL1-0shΔGR, to evaluate differential protein level alteration and redox regulation of these two cell lines. We identified 34 spots that exhibited marked changes in intensities, and 13 proteins showing significant changes in thiol reactivity, in response to GR depletion. Several proteins involved in redox regulation, calcium signaling, cytoskeleton regulation, and protein folding showed significant changes in expression, whereas proteins involved in redox regulation, protein folding, and glycolysis displayed changes in thiol reactivity. Interestingly, GR knockdown induces peroxiredoxin-1 overexpression in the air-exposed tissue and high oxygen consuming tissue such as cornea and liver, but not in the low oxygen consuming tissues such as breast and uterine. In summary, we used a comprehensive lung adenocarcinoma based proteomic approach for identifying GR-modulated protein expression alteration and redox modification. Based on our research, this is the first comprehensive proteomic and redox-proteomic analysis used to investigate the role of GR in a mammalian cell model.


Assuntos
Glutationa Redutase/metabolismo , Neoplasias Pulmonares/enzimologia , Proteoma/análise , Proteômica/métodos , Linhagem Celular Tumoral , Eletroforese em Gel Bidimensional , Técnicas de Silenciamento de Genes , Glutationa Redutase/genética , Humanos , Neoplasias Pulmonares/metabolismo , Oxirredução , Proteoma/química , Proteoma/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
7.
J Pharm Biomed Anal ; 78-79: 1-8, 2013 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-23425445

RESUMO

Doxorubicin is an anticancer drug used in a wide range of cancer therapies; however, doxorubicin-induced drug resistance is one of the most serious obstacles of cancer chemotherapy. Recent studies have indicated that reduced oxidative stress levels in cancer cells induce drug resistance. However, the redox-modifications of resistance - associated cellular targets are largely unknown. Thus, the current study employed cysteine-labeling based two-dimensional differential gel electrophoresis (2D-DIGE) combined with MALDI-TOF mass spectrometry (MALDI-TOF MS) to analyze the effect of doxorubicin resistance on redox regulation in uterine cancer and showed 33 spots that were significantly changed in thiol reactivity. These proteins involve cytoskeleton regulation, signal transduction, redox-regulation, glycolysis, and cell-cycle regulation. The current work shows that the redox 2D-DIGE-based proteomic strategy provides a rapid method to study the molecular mechanisms of doxorubicin-induced drug resistance in uterine cancer. The identified targets may be used to further evaluate their roles in drug-resistance formation and for possible diagnostic or therapeutic applications.


Assuntos
Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Proteômica , Compostos de Sulfidrila/metabolismo , Neoplasias Uterinas/tratamento farmacológico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Neoplasias Uterinas/metabolismo
8.
J Proteomics ; 77: 111-28, 2012 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-22813881

RESUMO

Retinopathy has been observed in around quarter of diabetic patients. Diabetic retinopathy can result in poor vision and even blindness since high glucose has been evidenced to weaken retinal capillary leading to leakage of blood into the surrounding space. In the present study, a proteomics-based approach has been applied to analyze a model retinal pigmented epithelium cell line, ARPE-19, grown in mannitol-balanced 5.5mM, 25 mM and 100 mM D-glucose culture media and used as a model for hyperglycemia secretomic analysis. Totally, 55 differentially secreted proteins have been firmly identified representing 46 unique gene products. These secreted proteins mainly function in cytoskeleton-associated adhesion/junction (such as galectin-3-binding protein) and transport (multidrug resistance-associated protein 1). Additionally, the identified secreted markers including asialoglycoprotein receptor 1, lysophosphatidic acid receptor 3, moesin, MPP2, haptoglobin and cathepsin D were further validated in plasma samples coming from type 2 diabetic patients with retinopathy and healthy donors. In summary, we report a comprehensive retinal cell-based proteomic approach for the identification of potential secreted retinal markers-induced in high glucose conditions. Some of these identified secreted proteins have been validated in diabetic retinopathy plasma demonstrating the potentially utilizing of these markers in screening and treating diabetic retinopathy.


Assuntos
Retinopatia Diabética/metabolismo , Células Epiteliais/metabolismo , Proteínas do Olho/metabolismo , Glucose/farmacologia , Proteoma/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Edulcorantes/farmacologia , Biomarcadores/metabolismo , Linhagem Celular , Retinopatia Diabética/patologia , Células Epiteliais/patologia , Glucose/metabolismo , Humanos , Modelos Biológicos , Epitélio Pigmentado da Retina/patologia , Edulcorantes/metabolismo
9.
J Agric Food Chem ; 52(13): 4057-63, 2004 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-15212448

RESUMO

Procedures were developed for the simultaneous determination of glyphosate [N-(phosphonomethyl)glycine] and glufosinate [dl-homoalanin-4-yl-(methyl)phosphinic acid] and their major metabolites, aminomethylphosphonic acid (AMPA) and 3-(methylphosphinico)propionic acid (3-MPPA), in rice and soybean sprouts by gas chromatography (GC) equipped with a pulsed flame photometric detector (PFPD). Herbicides and their major metabolites were previously derivatized with TMOA (trimethyl orthoacetate (TMOA) in the presence of acetic acid, and their GC responses versus heating temperature (70-90 degrees C) and heating time (30-120 min) were optimized. It was found that increases in heating temperature and heating time were unfavorable for the derivatization of glyphosate or glufosinate, whereas high temperature and extended reaction time remarkably facilitated that of AMPA and 3-MPPA except at 90 degrees C for an extended reaction time (120 min). Combination of AG1-X8 anion-exchange chromatography with a Florisil cartridge cleanup process was favorable for the GC-PFPD analysis. Four types of derivatives spiked in rice and soybean sprout matrices were eluted, reaching a baseline separation, in a sequence of 3-MPPA, AMPA, glyphosate, and glufosinate within 14 min using a DB-608 capillary column. Recoveries of glyphosate, AMPA, glufosinate, and 3-MPPA (0.5 ppm) spiked in both sample matrices were determined to be 72-81, 71-86, 101-119, and 83-90%, respectively, whereas the coefficient of variation was determined to be <10% in three repeated determinations. The instrumental limits of detection for glyphosate, AMPA, glufosinate, and 3-MPPA in sample matrices were 0.02, 0.03, 0.02, and 0.01 ppm, respectively. The limits of quantification for glyphosate, AMPA, glufosinate, and 3-MPPA in sample matrices were 0.06, 0.10, 0.06, and 0.04 ppm, respectively.


Assuntos
Aminobutiratos/análise , Cromatografia Gasosa/métodos , Glycine max/química , Glicina/análogos & derivados , Glicina/análise , Herbicidas/análise , Oryza/química , Ânions , Cromatografia por Troca Iônica , Isoxazóis , Organofosfonatos/análise , Propionatos/análise , Tetrazóis , Glifosato
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