Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 36
Filtrar
2.
Ther Deliv ; 13(4): 249-273, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35615860

RESUMO

Glioblastoma (GBM) is a deadly malignancy with a poor prognosis. An important factor contributing to GBM recurrence is high resistance of GBM cancer stem cells (GSCs). While temozolomide (TMZ), has been shown to consistently extend survival, GSCs grow resistant to TMZ through upregulation of DNA damage repair mechanisms and avoidance of apoptosis. Since a single-drug approach has failed to significantly alter prognosis in the past 15 years, unique approaches such as multidrug combination therapy together with distinctive targeted drug-delivery approaches against cancer stem cells are needed. In this review, a rationale for multidrug therapy using a targeted nanotechnology approach that preferentially target GSCs is proposed with discussion and examples of drugs, nanomedicine delivery systems, and targeting moieties.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Quimioterapia Combinada , Glioblastoma/tratamento farmacológico , Humanos , Hansenostáticos/farmacologia , Hansenostáticos/uso terapêutico , Células-Tronco Neoplásicas/patologia , Temozolomida/farmacologia , Temozolomida/uso terapêutico
3.
Radiol Artif Intell ; 4(1): e210301, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35146438
4.
Pharm Res ; 38(6): 1067-1079, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34100216

RESUMO

PURPOSE: Glioblastoma (GBM) is a malignant brain tumor with a poor long-term prognosis due to recurrence from highly resistant GBM cancer stem cells (CSCs), for which the current standard of treatment with temozolomide (TMZ) alone will unlikely produce a viable cure. In addition, CSCs regenerate rapidly and overexpress methyl transferase which overrides the DNA-alkylating mechanism of TMZ, leading to resistance. The objective of this research was to apply the concepts of nanotechnology to develop a multi-drug therapy, TMZ and idasanutlin (RG7388, a potent mouse double minute 2 (MDM2) antagonist), loaded in functionalized nanoparticles (NPs) that target the GBM CSC subpopulation, reduce the cell viability and provide possibility of in vivo preclinical imaging. METHODS: Polymer-micellar NPs composed of poly(styrene-b-ethylene oxide) (PS-b-PEO) and poly(lactic-co-glycolic) acid (PLGA) were developed by a double emulsion technique loading TMZ and/or RG7388. The NPs were covalently bound to a 15-nucleotide base-pair CD133 aptamer to target the CD133 antigen expressed on the surfaces of GBM CSCs. For diagnostic functionality, the NPs were labelled with radiotracer Zirconium-89 (89Zr). RESULTS: NPs maintained size range less than 100 nm, a low negative charge and exhibited the ability to target and kill the CSC subpopulation when TMZ and RG7388 were used in combination. The targeting function of CD133 aptamer promoted killing in GBM CSCs providing impetus for further development of targeted nanosystems for localized therapy in future in vivo models. CONCLUSIONS: This work has provided a potential clinical application for targeting GBM CSCs with simultaneous diagnostic imaging.


Assuntos
Antígeno AC133/metabolismo , Neoplasias Encefálicas/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Glioblastoma/metabolismo , Nanopartículas/metabolismo , Células-Tronco Neoplásicas/metabolismo , Animais , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Desenvolvimento de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Glioblastoma/tratamento farmacológico , Humanos , Camundongos , Micelas , Nanopartículas/administração & dosagem , Células-Tronco Neoplásicas/efeitos dos fármacos , Polímeros/administração & dosagem , Polímeros/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Pirrolidinas/administração & dosagem , Pirrolidinas/metabolismo , Temozolomida/administração & dosagem , Temozolomida/metabolismo , para-Aminobenzoatos/administração & dosagem , para-Aminobenzoatos/metabolismo
5.
Pharmaceutics ; 13(3)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33804222

RESUMO

The fate of intranasal aerosolized radiolabeled polymeric micellar nanoparticles (LPNPs) was tracked with positron emission tomography/computer tomography (PET/CT) imaging in a rat model to measure nose-to-brain delivery. A quantitative temporal and spatial testing protocol for new radio-nanotheranostic agents was sought in vivo. LPNPs labeled with a zirconium 89 (89Zr) PET tracer were administered via intranasal or intravenous delivery, followed by serial PET/CT imaging. After 2 h of continuous imaging, the animals were sacrificed, and the brain substructures (olfactory bulb, forebrain, and brainstem) were isolated. The activity in each brain region was measured for comparison with the corresponding PET/CT region of interest via activity measurements. Serial imaging of the LPNPs (100 nm PLA-PEG-DSPE+89Zr) delivered intranasally via nasal tubing demonstrated increased activity in the brain after 1 and 2 h following intranasal drug delivery (INDD) compared to intravenous administration, which correlated with ex vivo gamma counting and autoradiography. Although assessment of delivery from nose to brain is a promising approach, the technology has several limitations that require further development. An experimental protocol for aerosolized intranasal delivery is presented herein, which may provide a platform for better targeting the olfactory epithelium.

8.
Am J Nucl Med Mol Imaging ; 10(1): 1-31, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32211216

RESUMO

Intranasal (IN) delivery is a rapidly developing area for therapies with great potential for the treatment of central nervous system (CNS) diseases. Moreover, in vivo imaging is becoming an important part of therapy assessment, both clinically in humans and translationally in animals. IN drug delivery is an alternative to systemic administration that uses the direct anatomic pathway between the olfactory/trigeminal neuroepithelium of the nasal mucosa and the brain. Several drugs have already been approved for IN application, while others are undergoing development and testing. To better understand which imaging modalities are being used to assess IN delivery of therapeutics, we performed a literature search with the key words "Intranasal delivery" and "Imaging" and summarized these findings in the current review. While this review does not attempt to be fully comprehensive, we intend for the examples provided to allow a well-rounded picture of the imaging tools available to assess IN delivery, with an emphasis on the nose-to-brain delivery route. Examples of in vivo imaging, for both humans and animals, include magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), gamma scintigraphy and computed tomography (CT). Additionally, some in vivo optical imaging modalities, including bioluminescence and fluorescence, have been used more in experimental testing in animals. In this review, we introduce each imaging modality, how it is being utilized and outline its strengths and weaknesses, specifically in the context of IN delivery of therapeutics to the brain.

10.
IEEE Trans Med Imaging ; 39(1): 188-203, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31217097

RESUMO

In this paper, we present a semi-supervised deep learning approach to accurately recover high-resolution (HR) CT images from low-resolution (LR) counterparts. Specifically, with the generative adversarial network (GAN) as the building block, we enforce the cycle-consistency in terms of the Wasserstein distance to establish a nonlinear end-to-end mapping from noisy LR input images to denoised and deblurred HR outputs. We also include the joint constraints in the loss function to facilitate structural preservation. In this process, we incorporate deep convolutional neural network (CNN), residual learning, and network in network techniques for feature extraction and restoration. In contrast to the current trend of increasing network depth and complexity to boost the imaging performance, we apply a parallel 1×1 CNN to compress the output of the hidden layer and optimize the number of layers and the number of filters for each convolutional layer. The quantitative and qualitative evaluative results demonstrate that our proposed model is accurate, efficient and robust for super-resolution (SR) image restoration from noisy LR input images. In particular, we validate our composite SR networks on three large-scale CT datasets, and obtain promising results as compared to the other state-of-the-art methods.


Assuntos
Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação , Tomografia Computadorizada por Raios X/métodos , Abdome/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Tíbia/diagnóstico por imagem
11.
Pancreas ; 45(3): 370-5, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26390428

RESUMO

OBJECTIVES: In mouse models of pancreatic cancer, IPI-926, an oral Hedgehog inhibitor, increases chemotherapy delivery by depleting tumor-associated stroma. This multicenter phase Ib study evaluated IPI-926 in combination with FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, oxaliplatin) in patients with advanced pancreatic cancer. METHODS: Patients were treated with once-daily IPI-926 plus FOLFIRINOX. A 3 + 3 dose escalation design was used, with cohort expansion at the maximum tolerated dose. A subset of patients underwent perfusion computed tomography to assess changes in tumor perfusion. RESULTS: The maximum tolerated dose was identified 1 dose level below standard FOLFIRINOX. Common treatment-related adverse events included liver function test abnormalities, neuropathy, nausea/vomiting, and diarrhea. Objective response rate was high (67%), and patients receiving IPI-926 maintenance showed further declines in CA19-9 levels even after FOLFIRINOX discontinuation. Treatment did not result in consistent increases in tumor perfusion. The study closed early when a separate phase II trial of IPI-926 plus gemcitabine indicated detrimental effects of this combination. CONCLUSIONS: This is the first study to demonstrate the feasibility of using FOLFIRINOX as the chemotherapeutic backbone in a clinical trial design. Although robust antitumor activity and acceptable safety were observed with the addition of IPI-926 to this regimen, future development of Hedgehog inhibitors in pancreatic cancer seems unlikely.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/metabolismo , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno CA-19-9/metabolismo , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Diarreia/induzido quimicamente , Relação Dose-Resposta a Droga , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Proteínas Hedgehog/metabolismo , Humanos , Irinotecano , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Doenças do Sistema Nervoso/induzido quimicamente , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Neoplasias Pancreáticas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento , Alcaloides de Veratrum/administração & dosagem , Alcaloides de Veratrum/efeitos adversos , Alcaloides de Veratrum/farmacocinética , Vômito/induzido quimicamente
12.
Nat Rev Clin Oncol ; 12(11): 664-75, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26169924

RESUMO

Fractals are mathematical constructs that show self-similarity over a range of scales and non-integer (fractal) dimensions. Owing to these properties, fractal geometry can be used to efficiently estimate the geometrical complexity, and the irregularity of shapes and patterns observed in lung tumour growth (over space or time), whereas the use of traditional Euclidean geometry in such calculations is more challenging. The application of fractal analysis in biomedical imaging and time series has shown considerable promise for measuring processes as varied as heart and respiratory rates, neuronal cell characterization, and vascular development. Despite the advantages of fractal mathematics and numerous studies demonstrating its applicability to lung cancer research, many researchers and clinicians remain unaware of its potential. Therefore, this Review aims to introduce the fundamental basis of fractals and to illustrate how analysis of fractal dimension (FD) and associated measurements, such as lacunarity (texture) can be performed. We describe the fractal nature of the lung and explain why this organ is particularly suited to fractal analysis. Studies that have used fractal analyses to quantify changes in nuclear and chromatin FD in primary and metastatic tumour cells, and clinical imaging studies that correlated changes in the FD of tumours on CT and/or PET images with tumour growth and treatment responses are reviewed. Moreover, the potential use of these techniques in the diagnosis and therapeutic management of lung cancer are discussed.


Assuntos
Fractais , Processamento de Imagem Assistida por Computador , Neoplasias Pulmonares/patologia , Humanos , Modelos Biológicos
14.
Radiology ; 275(2): 448-57, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25559231

RESUMO

PURPOSE: To evaluate the performance and interobserver agreement of qualitative dynamic contrast material enhanced magnetic resonance (MR) imaging curve analysis as described in the Prostate Imaging Reporting and Data System (PI-RADS) for the differentiation of prostate cancer (PCa) from healthy prostatic tissue in the peripheral zone (PZ). MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act-compliant institutional review board-approved retrospective analysis included 120 consecutive pretreatment dynamic contrast-enhanced (DCE) MR imaging PCa examinations. Regions of interest (ROIs) were placed in 251 spots, including 95 (37.8%) in healthy PZ tissue and 156 (62.2%) in PCa, by using detailed histologic-multiparametric MR correlation review. Three radiologists reviewed the DCE time curves and assessed qualitative curve types as described in PI-RADS: type 1 (progressive), type 2 (plateau), or type 3 (washout). Receiver operating characteristic curve analysis was used to assess accuracy in differentiating PCa from healthy tissue on the basis of curve type, and κ was calculated to assess interobserver agreement. RESULTS: Receiver operating characteristic curves were similar for all observers, but mean areas under the receiver operating characteristic curve were poor (0.58 ± 0.04 [standard deviation] to 0.63 ± 0.04). No differences in accuracy were seen for varying DCE time resolution and imaging length. Observer agreement in assessment of type 3 versus types 1 or 2 curves was substantial (0.66 < κ < 0.79), better for PCa ROIs than for healthy-tissue ROIs. The agreement between type 1 and type 2 curves was moderate to substantial (0.49 < κ < 0.78). CONCLUSION: Qualitative DCE MR imaging time-curve-type analysis performs poorly for differentiation of PCa from healthy prostatic tissue. Interobserver agreement is excellent in assessment of type 3 curves but only moderate for type 1 and 2 curves.


Assuntos
Meios de Contraste , Imageamento por Ressonância Magnética/estatística & dados numéricos , Próstata/anatomia & histologia , Neoplasias da Próstata/patologia , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Retrospectivos
15.
Radiographics ; 34(7): 1885-905, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25384290

RESUMO

Computed tomography (CT) colonography is a screening modality used to detect colonic polyps before they progress to colorectal cancer. Computer-aided detection (CAD) is designed to decrease errors of detection by finding and displaying polyp candidates for evaluation by the reader. CT colonography CAD false-positive results are common and have numerous causes. The relative frequency of CAD false-positive results and their effect on reader performance on the basis of a 19-reader, 100-case trial shows that the vast majority of CAD false-positive results were dismissed by readers. Many CAD false-positive results are easily disregarded, including those that result from coarse mucosa, reconstruction, peristalsis, motion, streak artifacts, diverticulum, rectal tubes, and lipomas. CAD false-positive results caused by haustral folds, extracolonic candidates, diminutive lesions (<6 mm), anal papillae, internal hemorrhoids, varices, extrinsic compression, and flexural pseudotumors are almost always recognized and disregarded. The ileocecal valve and tagged stool are common sources of CAD false-positive results associated with reader false-positive results. Nondismissable CAD soft-tissue polyp candidates larger than 6 mm are another common cause of reader false-positive results that may lead to further evaluation with follow-up CT colonography or optical colonoscopy. Strategies for correctly evaluating CAD polyp candidates are important to avoid pitfalls from common sources of CAD false-positive results.


Assuntos
Pólipos do Colo/diagnóstico por imagem , Colonografia Tomográfica Computadorizada/métodos , Neoplasias Colorretais/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador , Reações Falso-Positivas , Humanos , Reconhecimento Automatizado de Padrão , Sensibilidade e Especificidade
17.
Proc Natl Acad Sci U S A ; 110(24): 9680-5, 2013 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-23720314

RESUMO

Researchers collaborate on scientific projects that are often measured by both the quantity and the quality of the resultant peer-reviewed publications. However, not all collaborators contribute to these publications equally, making metrics such as the total number of publications and the H-index insufficient measurements of individual scientific impact. To remedy this, we use an axiomatic approach to assign relative credits to the coauthors of a given paper, referred to as the A-index for its axiomatic foundation. In this paper, we use the A-index to compute the weighted sums of peer-reviewed publications and journal impact factors, denoted as the C- and P-indexes for collaboration and productivity, respectively. We perform an in-depth analysis of bibliometric data for 186 biomedical engineering faculty members and from extensive simulation. It is found that these axiomatically weighted indexes better capture a researcher's scientific caliber than do the total number of publications and the H-index, allowing for fairer and sharper evaluation of researchers with diverse collaborative behaviors.


Assuntos
Bibliometria , Pesquisa Biomédica/estatística & dados numéricos , Fator de Impacto de Revistas , Publicações Periódicas como Assunto/estatística & dados numéricos , Autoria/normas , Pesquisa Biomédica/normas , Comportamento Cooperativo , Eficiência , Humanos , Método de Monte Carlo , Revisão da Pesquisa por Pares/métodos , Publicações Periódicas como Assunto/normas , Pesquisadores/normas
18.
Acad Radiol ; 20(4): 486-92, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23498991

RESUMO

RATIONALE AND OBJECTIVES: There is potential for x-ray dose reduction in computed tomography colonography (CTC) relative to body mass index (BMI). We evaluated the association between BMI and three-dimensional (3D) CTC image quality to assess the potential utility of BMI as the basis for radiation dose reduction in CTC. MATERIALS AND METHODS: Ninety-six consecutive patients underwent CTC and were randomized for scanning at 15 or 30 mAs. Extremely obese patients (BMI > 50) were excluded. Each patient was scanned supine and prone on a multidetector CT scanner. Postprocessing CTC visualization was performed on a dedicated workstation. Three independent observers assessed 3D image quality using a four-point scale. Image noise was measured in both the abdomen and pelvis. The association between BMI and image noise was examined using random-effects linear regression models. Logistic regression was used to examine the relationship between BMI, mAs, and conspicuity scores. RESULTS: Statistically significant differences in image noise were observed between 15 and 30 mAs in both the abdomen and pelvis, and the difference was greater with increasing BMI. A positive relationship was detected between BMI and noise in the abdomen (P < .001) and pelvis (P < .001). Inverse correlation was identified between BMI and conspicuity scores in the abdomen (P = .01) and pelvis (P < .001). Overall conspicuity scores were reduced for both 15 and 30 mAs groups as BMI increased. CONCLUSION: The radiation dose for CTC can be reduced by 40% and 70% below commonly employed doses for overweight and normal BMI patients, respectively, by using a BMI-adjusted dose reduction approach. Conspicuity scores dropped in obese patients with reduced dose suggesting that standard accepted doses should be utilized in that group.


Assuntos
Índice de Massa Corporal , Colonografia Tomográfica Computadorizada , Doses de Radiação , Humanos , Imageamento Tridimensional
19.
Int J Radiat Oncol Biol Phys ; 85(2): 378-84, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-22717242

RESUMO

PURPOSE: To summarize the results of a 4-year period in which endorectal magnetic resonance imaging (MRI) was considered for all men referred for salvage radiation therapy (RT) at a single academic center; to describe the incidence and location of locally recurrent disease in a contemporary cohort of men with biochemical failure after radical prostatectomy (RP), and to identify prognostic variables associated with MRI findings in order to define which patients may have the highest yield of the study. METHODS AND MATERIALS: Between 2007 and 2011, 88 men without clinically palpable disease underwent eMRI for detectable prostate-specific antigen (PSA) after RP. The median interval between RP and eMRI was 32 months (interquartile range, 14-57 months), and the median PSA level was 0.30 ng/mL (interquartile range, 0.19-0.72 ng/mL). Magnetic resonance imaging scans consisting of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging were evaluated for features consistent with local recurrence. The prostate bed was scored from 0-4, whereby 0 was definitely normal, 1 probably normal, 2 indeterminate, 3 probably abnormal, and 4 definitely abnormal. Local recurrence was defined as having a score of 3-4. RESULTS: Local recurrence was identified in 21 men (24%). Abnormalities were best appreciated on T2-weighted axial images (90%) as focal hypointense lesions. Recurrence locations were perianastomotic (67%) or retrovesical (33%). The only risk factor associated with local recurrence was PSA; recurrence was seen in 37% of men with PSA >0.3 ng/mL vs 13% if PSA ≤0.3 ng/mL (P<.01). The median volume of recurrence was 0.26 cm(3) and was directly associated with PSA (r=0.5, P=.02). The correlation between MRI-based tumor volume and PSA was even stronger in men with positive margins (r=0.8, P<.01). CONCLUSIONS: Endorectal MRI can define areas of local recurrence after RP in a minority of men without clinical evidence of disease, with yield related to PSA. Further study is necessary to determine whether eMRI can improve patient selection and success of salvage RT.


Assuntos
Imageamento por Ressonância Magnética/métodos , Recidiva Local de Neoplasia/patologia , Próstata/patologia , Neoplasias da Próstata/patologia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/diagnóstico , Estadiamento de Neoplasias , Neoplasia Residual , Seleção de Pacientes , Próstata/cirurgia , Antígeno Prostático Específico/sangue , Prostatectomia/métodos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/cirurgia , Terapia de Salvação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA