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1.
Cell ; 151(6): 1185-99, 2012 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-23217706

RESUMO

Reprogramming of cellular metabolism is a key event during tumorigenesis. Despite being known for decades (Warburg effect), the molecular mechanisms regulating this switch remained unexplored. Here, we identify SIRT6 as a tumor suppressor that regulates aerobic glycolysis in cancer cells. Importantly, loss of SIRT6 leads to tumor formation without activation of known oncogenes, whereas transformed SIRT6-deficient cells display increased glycolysis and tumor growth, suggesting that SIRT6 plays a role in both establishment and maintenance of cancer. By using a conditional SIRT6 allele, we show that SIRT6 deletion in vivo increases the number, size, and aggressiveness of tumors. SIRT6 also functions as a regulator of ribosome metabolism by corepressing MYC transcriptional activity. Lastly, Sirt6 is selectively downregulated in several human cancers, and expression levels of SIRT6 predict prognosis and tumor-free survival rates, highlighting SIRT6 as a critical modulator of cancer metabolism. Our studies reveal SIRT6 to be a potent tumor suppressor acting to suppress cancer metabolism.


Assuntos
Neoplasias/metabolismo , Sirtuínas/metabolismo , Animais , Proliferação de Células , Regulação para Baixo , Fibroblastos/metabolismo , Técnicas de Inativação de Genes , Glicólise , Humanos , Camundongos , Camundongos Nus , Camundongos SCID , Transplante de Neoplasias , Proteínas Proto-Oncogênicas c-myc/metabolismo , Sirtuínas/genética , Transcrição Gênica , Transplante Heterólogo , Proteínas Supressoras de Tumor/genética
2.
Cell ; 149(3): 656-70, 2012 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-22541435

RESUMO

Tumor maintenance relies on continued activity of driver oncogenes, although their rate-limiting role is highly context dependent. Oncogenic Kras mutation is the signature event in pancreatic ductal adenocarcinoma (PDAC), serving a critical role in tumor initiation. Here, an inducible Kras(G12D)-driven PDAC mouse model establishes that advanced PDAC remains strictly dependent on Kras(G12D) expression. Transcriptome and metabolomic analyses indicate that Kras(G12D) serves a vital role in controlling tumor metabolism through stimulation of glucose uptake and channeling of glucose intermediates into the hexosamine biosynthesis and pentose phosphate pathways (PPP). These studies also reveal that oncogenic Kras promotes ribose biogenesis. Unlike canonical models, we demonstrate that Kras(G12D) drives glycolysis intermediates into the nonoxidative PPP, thereby decoupling ribose biogenesis from NADP/NADPH-mediated redox control. Together, this work provides in vivo mechanistic insights into how oncogenic Kras promotes metabolic reprogramming in native tumors and illuminates potential metabolic targets that can be exploited for therapeutic benefit in PDAC.


Assuntos
Adenocarcinoma/metabolismo , Modelos Animais de Doenças , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Animais , Humanos , Camundongos , Proteínas Proto-Oncogênicas p21(ras)/genética , Transcrição Gênica
3.
Proc Natl Acad Sci U S A ; 118(48)2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34815335

RESUMO

During pregnancy, the rodent liver undergoes hepatocyte proliferation and increases in size, followed by weaning-induced involution via hepatocyte cell death and stromal remodeling, creating a prometastatic niche. These data suggest a mechanism for increased liver metastasis in breast cancer patients with recent childbirth. It is unknown whether the human liver changes in size and function during pregnancy and weaning. In this study, abdominal imaging was obtained in healthy women at early and late pregnancy and postwean. During pregnancy time points, glucose production and utilization and circulating bile acids were measured. Independently of weight gain, most women's livers increased in size with pregnancy, then returned to baseline postwean. Putative roles for bile acids in liver growth and regression were observed. Together, the data support the hypothesis that the human liver is regulated by reproductive state with growth during pregnancy and volume loss postwean. These findings have implications for sex-specific liver diseases and for breast cancer outcomes.


Assuntos
Fígado/fisiologia , Tamanho do Órgão/fisiologia , Gravidez/fisiologia , Adulto , Ácidos e Sais Biliares/análise , Ácidos e Sais Biliares/sangue , Proliferação de Células , Feminino , Glucose/análise , Hepatócitos , Humanos , Fígado/metabolismo , Parto , Desmame
4.
Magn Reson Med ; 88(1): 151-163, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35324040

RESUMO

PURPOSE: Seiffert spirals were recently explored as an efficient way to traverse 3D k-space compared to traditional 3D techniques. Several studies have shown the ability of 3D MR fingerprinting (MRF) techniques to acquire T1 and T2 relaxation maps in a short period of time. However, these sequences do not sample across a large region of 3D k-space every TR, especially in the way that Seiffert trajectories can. METHODS: A 3D MRF sequence was designed using 8 Seiffert spirals rotated in 3D k-space, with flip angle modulation for T1 and T2 sensitivity. The sequence was compared to an MRF sequence using a 2D spiral rotated in 3D k-space using the tiny golden angle acquisition with similar resolution/readout duration. Both sequences were evaluated using simulations, phantom validation, and in vivo imaging. RESULTS: In all experiments, the Seiffert spiral MRF sequence performed similar to if not better than the multi-axis 2D spiral MRF sequence. Strong intraclass correlation coefficients (> 0.9) were found between conventional and MRF sequences in phantoms, whereas the in vivo results showed slightly less aliasing artifact with the Seiffert trajectory. CONCLUSION: In this study, Seiffert spirals were used within the MRF framework to acquire high-resolution T1 and T2 relaxation time maps in less than 2.5 min. The reduced aliasing artifacts seen with the Seiffert sequence suggests that sampling over 3D k-space evenly each TR can improve quantification or shorten scan times.


Assuntos
Encéfalo , Processamento de Imagem Assistida por Computador , Artefatos , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Imagens de Fantasmas
5.
NMR Biomed ; 33(5): e4284, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32125050

RESUMO

T1ρ relaxation imaging is a quantitative imaging technique that has been used to assess cartilage integrity, liver fibrosis, tumors, cardiac infarction, and Alzheimer's disease. T1 , T2 , and T1ρ relaxation time constants have each demonstrated different degrees of sensitivity to several markers of fibrosis and inflammation, allowing for a potential multi-parametric approach to tissue quantification. Traditional magnetic resonance fingerprinting (MRF) has been shown to provide quick, quantitative mapping of T1 and T2 relaxation time constants. In this study, T1ρ relaxation is added to the MRF framework using spin lock preparations. An MRF sequence involving an RF-spoiled sequence with TR , flip angle, T1ρ , and T2 preparation variation is described. The sequence is then calibrated against conventional T1 , T2 , and T1ρ relaxation mapping techniques in agar phantoms and the abdomens of four healthy volunteers. Strong intraclass correlation coefficients (ICC > 0.9) were found between conventional and MRF sequences in phantoms and also in healthy volunteers (ICC > 0.8). The highest ICC correlation values were seen in T1 , followed by T1ρ and then T2 . In this study, T1ρ relaxation has been incorporated into the MRF framework by using spin lock preparations, while still fitting for T1 and T2 relaxation time constants. The acquisition of these parameters within a single breath hold in the abdomen alleviates the issues of movement between breath holds in conventional techniques.


Assuntos
Imageamento por Ressonância Magnética , Adulto , Feminino , Humanos , Masculino , Imagens de Fantasmas
6.
J Transl Med ; 16(1): 358, 2018 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-30551737

RESUMO

BACKGROUND: In order to establish the workflows required to implement a real-time process involving multi-omic analysis of patient samples to support precision-guided therapeutic intervention, a tissue acquisition and analysis trial was implemented. This report describes our findings to date, including the frequency with which mutational testing led to precision-guided therapy and outcome for those patients. METHODS: Eligible patients presenting to Oregon Health and Science University Knight Cancer Institute were enrolled on the study. Patients with biopsy proven metastatic or locally advanced unresectable prostate cancer, breast cancer, pancreatic adenocarcinoma, or refractory acute myelogenous leukemia receiving standard of care therapy were eligible. Metastatic site biopsies were collected and analyzed using the Knight Diagnostic Lab GeneTrails comprehensive solid tumor panel (124 genes). CLIA certified genomic information was made available to the treating physician. RESULTS: Between 1/26/2017 and 5/30/2018, 38 patients were enrolled, with 28 successfully undergoing biopsy. Of these, 25 samples yielded sufficient tumor for analysis. The median biopsy cellularity and number of cores collected were 70% (15-90%) and 5 (2-20), respectively. No procedure-related complications occurred. GeneTrails analysis revealed that 22 of 25 (88%) tumor samples harbored at least one potentially actionable mutation, and 18 (72%) samples harbored 2 or more potentially actionable mutations. The most common genetic alterations identified involved: DNA damage repair genes, cell cycle regulating genes, PIK3CA/Akt/mTOR pathway, and FGF gene family. To date, CLIA certified genomic results were used by treating physicians for precision-guided therapy in 5 (23%) patients. CONCLUSION: We report the feasibility of real-time tissue acquisition and analysis to support a successful translational oncology platform. The workflow will provide the foundation to improve access and accrual to biomarker driven precision oncology trials.


Assuntos
Oncologia , Terapia de Alvo Molecular , Pesquisa Translacional Biomédica , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Estudos de Coortes , Evolução Fatal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Mutação
7.
NMR Biomed ; 31(9): e3951, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30011109

RESUMO

The use of quantitative imaging biomarkers in the imaging of various disease states, including cancer and neurodegenerative disease, has increased in recent years. T1 , T2 , and T2 * relaxation time constants have been shown to be affected by tissue structure or contrast infusion. Acquiring these biomarkers simultaneously in a multi-parametric acquisition could provide more robust detection of tissue changes in various disease states including neurodegeneration and cancer. Traditional magnetic resonance fingerprinting (MRF) has been shown to provide quick, quantitative mapping of T1 and T2 relaxation time constants. In this study, T2 * relaxation is added to the MRF framework using variable echo times (TE). To demonstrate the feasibility of the method and compare incremental and golden angle spiral rotations, simulated phantom data was fit using the proposed method. Additionally, T1 /T2 /T2 */δf MRF as well as conventional T1 , T2 , and T2 * acquisitions were acquired in agar phantoms and the brains of three healthy volunteers. Golden angle spiral rotation was found to reduce inaccuracy resulting from off resonance effects. Strong correlations were found between conventional and MRF values in the T1 , T2 , and T2 * relaxation time constants of the agar phantoms and healthy volunteers. In this study, T2 * relaxation has been incorporated into the MRF framework by using variable echo times, while still fitting for T1 and T2 relaxation time constants. In addition to fitting these relaxation time constants, a novel method for fitting and correcting off resonance effects has been developed.


Assuntos
Imageamento por Ressonância Magnética , Adulto , Encéfalo/diagnóstico por imagem , Simulação por Computador , Feminino , Humanos , Masculino , Análise Numérica Assistida por Computador , Imagens de Fantasmas , Razão Sinal-Ruído , Fatores de Tempo , Adulto Jovem
8.
Kidney Int ; 92(1): 47-66, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28434822

RESUMO

Contrast-enhanced magnetic resonance imaging is a commonly used diagnostic tool. Compared with standard gadolinium-based contrast agents, ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, MA), used as an alternative contrast medium, is feasible in patients with impaired renal function. Other attractive imaging features of i.v. ferumoxytol include a prolonged blood pool phase and delayed intracellular uptake. With its unique pharmacologic, metabolic, and imaging properties, ferumoxytol may play a crucial role in future magnetic resonance imaging of the central nervous system, various organs outside the central nervous system, and the cardiovascular system. Preclinical and clinical studies have demonstrated the overall safety and effectiveness of this novel contrast agent, with rarely occurring anaphylactoid reactions. The purpose of this review is to describe the general and organ-specific properties of ferumoxytol, as well as the advantages and potential pitfalls associated with its use in magnetic resonance imaging. To more fully demonstrate the applications of ferumoxytol throughout the body, an imaging atlas was created and is available online as supplementary material.


Assuntos
Meios de Contraste/administração & dosagem , Óxido Ferroso-Férrico/administração & dosagem , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Animais , Atlas como Assunto , Pré-Escolar , Meios de Contraste/efeitos adversos , Meios de Contraste/farmacocinética , Feminino , Óxido Ferroso-Férrico/efeitos adversos , Óxido Ferroso-Férrico/farmacocinética , Hematínicos/administração & dosagem , Humanos , Rim/fisiopatologia , Imageamento por Ressonância Magnética/efeitos adversos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Eliminação Renal , Insuficiência Renal Crônica/fisiopatologia , Reprodutibilidade dos Testes
10.
Radiology ; 277(3): 813-25, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26267831

RESUMO

Although investigators in the imaging community have been active in developing and evaluating quantitative imaging biomarkers (QIBs), the development and implementation of QIBs have been hampered by the inconsistent or incorrect use of terminology or methods for technical performance and statistical concepts. Technical performance is an assessment of how a test performs in reference objects or subjects under controlled conditions. In this article, some of the relevant statistical concepts are reviewed, methods that can be used for evaluating and comparing QIBs are described, and some of the technical performance issues related to imaging biomarkers are discussed. More consistent and correct use of terminology and study design principles will improve clinical research, advance regulatory science, and foster better care for patients who undergo imaging studies.


Assuntos
Biomarcadores/análise , Diagnóstico por Imagem/métodos , Viés , Imagens de Fantasmas , Valores de Referência , Reprodutibilidade dos Testes , Terminologia como Assunto
11.
Radiographics ; 35(5): 1439-60, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26207581

RESUMO

Body magnetic resonance (MR) imaging is challenging because of the complex interaction of multiple factors, including motion arising from respiration and bowel peristalsis, susceptibility effects secondary to bowel gas, and the need to cover a large field of view. The combination of these factors makes body MR imaging more prone to artifacts, compared with imaging of other anatomic regions. Understanding the basic MR physics underlying artifacts is crucial to recognizing the trade-offs involved in mitigating artifacts and improving image quality. Artifacts can be classified into three main groups: (a) artifacts related to magnetic field imperfections, including the static magnetic field, the radiofrequency (RF) field, and gradient fields; (b) artifacts related to motion; and (c) artifacts arising from methods used to sample the MR signal. Static magnetic field homogeneity is essential for many MR techniques, such as fat saturation and balanced steady-state free precession. Susceptibility effects become more pronounced at higher field strengths and can be ameliorated by using spin-echo sequences when possible, increasing the receiver bandwidth, and aligning the phase-encoding gradient with the strongest susceptibility gradients, among other strategies. Nonuniformities in the RF transmit field, including dielectric effects, can be minimized by applying dielectric pads or imaging at lower field strength. Motion artifacts can be overcome through respiratory synchronization, alternative k-space sampling schemes, and parallel imaging. Aliasing and truncation artifacts derive from limitations in digital sampling of the MR signal and can be rectified by adjusting the sampling parameters. Understanding the causes of artifacts and their possible solutions will enable practitioners of body MR imaging to meet the challenges of novel pulse sequence design, parallel imaging, and increasing field strength.


Assuntos
Artefatos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Tecido Adiposo/patologia , Conversão Análogo-Digital , Imagem Ecoplanar/instrumentação , Imagem Ecoplanar/métodos , Desenho de Equipamento , Falha de Equipamento , Humanos , Imageamento por Ressonância Magnética/instrumentação , Espectroscopia de Ressonância Magnética/instrumentação , Magnetismo , Movimento (Física) , Sensibilidade e Especificidade , Vísceras/patologia
12.
Radiographics ; 35(5): 1393-418, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26252365

RESUMO

In the past decade, image-guided targeted treatments such as percutaneous ablation, intra-arterial embolic therapies, and targeted radiation therapy have shown substantial promise in management of hepatobiliary malignancies. Imaging is integral to patient selection, treatment delivery, and assessment of treatment effectiveness. Preprocedural imaging is crucial and allows local tumor staging, evaluation of surrounding structures, and selection of suitable therapeutic options and strategies for treatment delivery. Postprocedural imaging is required to monitor therapeutic success, detect residual or recurrent disease, and identify procedure-related complications to guide appropriate future therapy. Technical innovations in cross-sectional imaging techniques such as computed tomography (CT) and magnetic resonance (MR) imaging, combined with advances in image postprocessing and new types of contrast agents, allow precise morphologic assessment and functional evaluation of hepatobiliary tumors. Advanced postprocessing techniques such as image fusion and volumetric assessment not only facilitate procedural planning and treatment delivery but also enhance posttreatment imaging surveillance. In addition, molecular imaging techniques such as fluorodeoxyglucose positron emission tomography (PET), PET/CT, and PET/MR imaging offer opportunities to evaluate various physiologic properties of tumors.


Assuntos
Neoplasias do Sistema Biliar/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Imagem Multimodal/métodos , Radioterapia Guiada por Imagem/métodos , Cirurgia Assistida por Computador/métodos , Neoplasias do Sistema Biliar/patologia , Neoplasias do Sistema Biliar/radioterapia , Neoplasias do Sistema Biliar/cirurgia , Ablação por Cateter , Meios de Contraste , Embolização Terapêutica , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Humanos , Interpretação de Imagem Assistida por Computador , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons/métodos , Cuidados Pré-Operatórios , Terapia com Prótons , Compostos Radiofarmacêuticos , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
13.
Abdom Imaging ; 40(6): 1374-86, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26025348

RESUMO

Simultaneous data collection for positron emission tomography and magnetic resonance imaging (PET/MR) is now a reality. While the full benefits of concurrently acquiring PET and MR data and the potential added clinical value are still being evaluated, initial studies have identified several important potential pitfalls in the interpretation of fluorodeoxyglucose (FDG) PET/MRI in oncologic whole-body imaging, the majority of which being related to the errors in the attenuation maps created from the MR data. The purpose of this article was to present such pitfalls and artifacts using case examples, describe their etiology, and discuss strategies to overcome them. Using a case-based approach, we will illustrate artifacts related to (1) Inaccurate bone tissue segmentation; (2) Inaccurate air cavities segmentation; (3) Motion-induced misregistration; (4) RF coils in the PET field of view; (5) B0 field inhomogeneity; (6) B1 field inhomogeneity; (7) Metallic implants; (8) MR contrast agents.


Assuntos
Erros de Diagnóstico , Fluordesoxiglucose F18 , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Imagem Corporal Total , Humanos , Imagem Multimodal , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes
14.
Am J Physiol Renal Physiol ; 307(1): F116-21, 2014 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-24808534

RESUMO

The intrarenal dopamine system is important for signaling and natriuresis, and significant dysfunction is associated with hypertension and kidney disease in ex vivo studies. Dopamine receptors also modulate and are modulated by the renin-angiotensin-aldosterone system. Here, we show the first in vivo measurement of D1-like receptors in the renal cortex of Sprague-Dawley rat and Papio anubis baboon using [(11)C]NNC 112, a positron emission tomography radioligand for D1-like receptors. In addition, we show a D1-like binding potential response to angiotensin II blockade in rats using losartan. Demonstration of self-saturable binding in the rat as well as specific and saturable binding in Papio anubis validate the use of [(11)C]NNC 112 in the first in vivo measurement of renal dopamine D1-like receptors. Furthermore, [(11)C]NNC 112 is a radioligand tool already validated for use in probing human central nervous system (CNS) D1-like receptors. Our work demonstrates specific and saturable non-CNS binding in higher animals and the ability to quantify physiological response to drug treatment and provides a clear path to extend use of [(11)C]NNC 112 to study renal dopamine in humans.


Assuntos
Dopamina/metabolismo , Rim/metabolismo , Receptores de Dopamina D1/metabolismo , Animais , Benzazepinas/farmacologia , Benzofuranos/farmacologia , Modelos Animais de Doenças , Antagonistas de Dopamina/farmacologia , Papio anubis , Tomografia por Emissão de Pósitrons , Ensaio Radioligante , Ratos , Ratos Sprague-Dawley , Sistema Renina-Angiotensina/efeitos dos fármacos
15.
Radiographics ; 34(3): 589-612, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24819783

RESUMO

Dual-energy computed tomographic (DECT) technology offers enhanced capabilities that may benefit oncologic imaging in the abdomen. By using two different energies, dual-energy CT allows material decomposition on the basis of energy-dependent attenuation profiles of specific materials. Although image acquisition with dual-energy CT is similar to that with single-energy CT, comprehensive postprocessing is able to generate not only images that are similar to single-energy CT (SECT) images, but a variety of other images, such as virtual unenhanced (VUE), virtual monochromatic (VMC), and material-specific iodine images. An increase in the conspicuity of iodine on low-energy VMC images and material-specific iodine images may aid detection and characterization of tumors. Use of VMC images of a desired energy level (40-140 keV) improves lesion-to-background contrast and the quality of vascular imaging for preoperative planning. Material-specific iodine images enable differentiation of hypoattenuating tumors from hypo- or hyperattenuating cysts and facilitate detection of isoattenuating tumors, such as pancreatic masses and peritoneal disease, thereby defining tumor targets for imaging-guided therapy. Moreover, quantitative iodine mapping may serve as a surrogate biomarker for monitoring effects of the treatment. Dual-energy CT is an innovative imaging technique that enhances the capabilities of CT in evaluating oncology patients.


Assuntos
Neoplasias Abdominais/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Radiografia Abdominal/métodos , Neoplasias Abdominais/terapia , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/efeitos da radiação , Artefatos , Meios de Contraste/efeitos adversos , Diagnóstico Diferencial , Neoplasias do Sistema Digestório/diagnóstico por imagem , Neoplasias do Sistema Digestório/terapia , Humanos , Compostos de Iodo/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Urogenitais/diagnóstico por imagem , Neoplasias Urogenitais/terapia , Vísceras/diagnóstico por imagem , Vísceras/efeitos da radiação
16.
Paediatr Anaesth ; 24(9): 1009-11, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25039494

RESUMO

Currently, information about airway assessment and tracheal intubation is communicated verbally or in writing. Google Glass can record this information in real time with minimal disruption to work flow, using standard operating room lighting.


Assuntos
Computadores de Mão , Intubação Intratraqueal , Gravação em Vídeo/instrumentação , Adulto , Humanos , Laringoscopia , Masculino , Adulto Jovem
18.
Oncologist ; 18(5): 543-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23657686

RESUMO

The objective of our retrospective institutional experience is to report the overall response rate, R0 resection rate, progression-free survival, and safety/toxicity of neoadjuvant FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan, and leucovorin) and chemoradiation in patients with locally advanced pancreatic cancer (LAPC). Patients with LAPC treated with FOLFIRINOX were identified via the Massachusetts General Hospital Cancer Center pharmacy database. Demographic information, clinical characteristics, and safety/tolerability data were compiled. Formal radiographic review was performed to determine overall response rates (ORRs). Twenty-two patients with LAPC began treatment with FOLFIRINOX between July 2010 and February 2012. The ORR was 27.3%, and the median progression-free survival was 11.7 months. Five of 22 patients were able to undergo R0 resections following neoadjuvant FOLFIRINOX and chemoradiation. Three of the five patients have experienced distant recurrence within 5 months. Thirty-two percent of patients required at least one emergency department visit or hospitalization while being treated with FOLFIRINOX. FOLFIRINOX possesses substantial activity in patients with LAPC. The use of FOLFIRINOX was associated with conversion to resectability in >20% of patients. However, the recurrences following R0 resection in three of five patients and the toxicities observed with the use of this regimen raise important questions about how to best treat patients with LAPC.


Assuntos
Camptotecina/análogos & derivados , Fluoruracila/administração & dosagem , Leucovorina/administração & dosagem , Compostos Organoplatínicos/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/administração & dosagem , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Irinotecano , Masculino , Massachusetts , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oxaliplatina , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/radioterapia , Resultado do Tratamento
19.
Radiology ; 269(3): 857-69, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24009348

RESUMO

PURPOSE: To compare the clinical impact of combined positron emission tomography (PET) and magnetic resonance (MR) imaging to that of combined PET and computed tomography (CT) performed on the same day in patients with cancer. MATERIALS AND METHODS: This HIPAA-compliant retrospective study was approved by the institutional review board. Patients gave written informed consent for study enrollment, including the possibility to use their imaging and clinical data in future evaluations. A total of 134 patients with cancer with a non-central nervous system primary neoplasm underwent same-day fluorodeoxyglucose (FDG) PET/CT and FDG PET/MR imaging. PET/CT and PET/MR studies were independently interpreted by teams of radiologists and nuclear medicine physicians. Four readers, divided into two teams composed of one radiologist and one nuclear medicine physician each, read all 134 studies. The referring physician classified discordance between PET/CT and PET/MR observations either as findings affecting clinical management or as findings not affecting clinical management. Data were compared with the χ(2) test. RESULTS: Findings affecting clinical management were noted for PET/CT studies but not for PET/MR studies in two (1.5%) of 134 patients and for PET/MR studies but not for PET/CT studies in 24 (17.9%) of 134 patients. The discrepancies between findings affecting clinical management detected with PET/MR imaging over those detected with PET/CT were significant (P < .001). CONCLUSION: In these patients, PET/MR imaging alone contributed to clinical management more often than did PET/CT alone. PET/MR imaging provides information that affects the care of patients with cancer and is unavailable from PET/CT. Online supplemental material is available for this article.


Assuntos
Imagem Multimodal , Neoplasias/patologia , Meios de Contraste , Feminino , Fluordesoxiglucose F18 , Gadolínio DTPA , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
20.
Acad Radiol ; 30(2): 215-229, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36411153

RESUMO

This paper is the fifth in a five-part series on statistical methodology for performance assessment of multi-parametric quantitative imaging biomarkers (mpQIBs) for radiomic analysis. Radiomics is the process of extracting visually imperceptible features from radiographic medical images using data-driven algorithms. We refer to the radiomic features as data-driven imaging markers (DIMs), which are quantitative measures discovered under a data-driven framework from images beyond visual recognition but evident as patterns of disease processes irrespective of whether or not ground truth exists for the true value of the DIM. This paper aims to set guidelines on how to build machine learning models using DIMs in radiomics and to apply and report them appropriately. We provide a list of recommendations, named RANDAM (an abbreviation of "Radiomic ANalysis and DAta Modeling"), for analysis, modeling, and reporting in a radiomic study to make machine learning analyses in radiomics more reproducible. RANDAM contains five main components to use in reporting radiomics studies: design, data preparation, data analysis and modeling, reporting, and material availability. Real case studies in lung cancer research are presented along with simulation studies to compare different feature selection methods and several validation strategies.


Assuntos
Neoplasias Pulmonares , Imageamento por Ressonância Magnética Multiparamétrica , Humanos , Curva ROC , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Diagnóstico por Imagem , Neoplasias Pulmonares/diagnóstico por imagem , Pulmão
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