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1.
Adv Funct Mater ; 34(24)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-39021614

RESUMO

Designing plasmonic nanoparticles for biomedical photoacoustic (PA) imaging involves tailoring material properties at the nanometer scale. A key in developing plasmonic PA contrast nanoagents is to engineer their enhanced optical responses in the near-infrared wavelength range, as well as heat transfer properties and photostability. This study introduces anisotropic plasmonic nanosphere aggregates with close interparticle proximity as photostable and efficient contrast agent for PA imaging. Silver (Ag), among plasmonic metals, is particularly attractive due to its strongest optical response and highest heat conductivity. Our results demonstrate that close interparticle proximity in silver nanoaggregates (AgNAs), spatially confined within a polymer shell layer, leads to blackbody-like optical absorption, resulting in robust PA signals through efficient pulsed heat generation and transfer. Additionally, our AgNAs exhibit a high photodamage threshold highlighting their potential to outperform conventional plasmonic contrast agents for high-contrast PA imaging over multiple imaging sessions. Furthermore, we demonstrate the capability of the AgNAs for molecular PA cancer imaging in vivo by incorporating a tumor-targeting peptide moiety.

2.
Rapid Commun Mass Spectrom ; 38(6): e9657, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38342682

RESUMO

RATIONALE: Characterization of Regolith And Trace Economic Resources (CRATER), an Orbitrap™-based laser desorption mass spectrometry instrument designed to conduct high-precision, spatially resolved analyses of planetary materials, is capable of answering outstanding science questions about the Moon's formation and the subsequent processes that have modified its (sub)surface. METHODS: Here, we describe the baseline design of the CRATER flight model, which requires <20 000 cm3  volume, <10 kg mass, and <60 W peak power. The analytical capabilities and performance metrics of a prototype that meets the full functionality of the flight model are demonstrated. RESULTS: The instrument comprises a high-power, solid-state, pulsed ultraviolet (213 nm) laser source to ablate the surface of the lunar sample, a custom ion optical interface to accelerate and collimate the ions produced at the ablation site, and an Orbitrap mass analyzer capable of discriminating competing isobars via ultrahigh mass resolution and high mass accuracy. The CRATER instrument can measure elemental and isotopic abundances and characterize the organic content of lunar surface samples, as well as identify economically valuable resources for future exploration. CONCLUSION: An engineering test unit of the flight model is currently in development to serve as a pathfinder for near-term mission opportunities.

3.
Eur Heart J ; 44(46): 4878-4889, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36806405

RESUMO

AIMS: The most appropriate timing of exercise therapy to improve cardiorespiratory fitness (CRF) among patients initiating chemotherapy is not known. The effects of exercise therapy administered during, following, or during and following chemotherapy were examined in patients with breast cancer. METHODS AND RESULTS: Using a parallel-group randomized trial design, 158 inactive women with breast cancer initiating (neo)adjuvant chemotherapy were allocated to receive (1:1 ratio): usual care or one of three exercise regimens-concurrent (during chemotherapy only), sequential (after chemotherapy only), or concurrent and sequential (continuous) (n = 39/40 per group). Exercise consisted of treadmill walking three sessions/week, 20-50 min at 55%-100% of peak oxygen consumption (VO2peak) for ≈16 (concurrent, sequential) or ≈32 (continuous) consecutive weeks. VO2peak was evaluated at baseline (pre-treatment), immediately post-chemotherapy, and ≈16 weeks after chemotherapy. In intention-to-treat analysis, there was no difference in the primary endpoint of VO2peak change between concurrent exercise and usual care during chemotherapy vs. VO2peak change between sequential exercise and usual care after chemotherapy [overall difference, -0.88 mL O2·kg-1·min-1; 95% confidence interval (CI): -3.36, 1.59, P = 0.48]. In secondary analysis, continuous exercise, approximately equal to twice the length of the other regimens, was well-tolerated and the only strategy associated with significant improvements in VO2peak from baseline to post-intervention (1.74 mL O2·kg-1·min-1, P < 0.001). CONCLUSION: There was no statistical difference in CRF improvement between concurrent vs. sequential exercise therapy relative to usual care in women with primary breast cancer. The promising tolerability and CRF benefit of ≈32 weeks of continuous exercise therapy warrant further evaluation in larger trials.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Qualidade de Vida , Consumo de Oxigênio , Terapia por Exercício/métodos , Quimioterapia Adjuvante
4.
Chem Rev ; 121(18): 11385-11457, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-33938724

RESUMO

Advances in hydrogel technology have unlocked unique and valuable capabilities that are being applied to a diverse set of translational applications. Hydrogels perform functions relevant to a range of biomedical purposes-they can deliver drugs or cells, regenerate hard and soft tissues, adhere to wet tissues, prevent bleeding, provide contrast during imaging, protect tissues or organs during radiotherapy, and improve the biocompatibility of medical implants. These capabilities make hydrogels useful for many distinct and pressing diseases and medical conditions and even for less conventional areas such as environmental engineering. In this review, we cover the major capabilities of hydrogels, with a focus on the novel benefits of injectable hydrogels, and how they relate to translational applications in medicine and the environment. We pay close attention to how the development of contemporary hydrogels requires extensive interdisciplinary collaboration to accomplish highly specific and complex biological tasks that range from cancer immunotherapy to tissue engineering to vaccination. We complement our discussion of preclinical and clinical development of hydrogels with mechanical design considerations needed for scaling injectable hydrogel technologies for clinical application. We anticipate that readers will gain a more complete picture of the expansive possibilities for hydrogels to make practical and impactful differences across numerous fields and biomedical applications.


Assuntos
Hidrogéis , Engenharia Tecidual , Próteses e Implantes
5.
Bioconjug Chem ; 33(12): 2320-2331, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-35156818

RESUMO

Despite significant research regarding metastasis, there has been limited success in preventing it. However, gold nanoparticle (AuNP) technology has shown the potential to inhibit metastasis. Our earlier studies of gold nanorod-assisted plasmonic photothermal therapy (AuNRs-PPTT), where gold nanorods (AuNRs) were irradiated with near-infrared (NIR) light to induce heat, were utilized in slowing cancer cell migration in vitro. Herein, we have expanded the in vitro studies of the AuNRs-PPTT to xenograft mice to inhibit metastasis of mammary gland tumors. The study duration was 32 days from 4T1 cancer cell injections in four treatment groups: control (PBS), NIR Only, AuNRs, and AuNRs + NIR. Multiple AuNRs-PPTT treatment sessions with intratumoral AuNRs injections were conducted every 7 days on average on the mice. Photoacoustic spectroscopy has been utilized to study the distribution and aggregation of AuNRs within the tumors and the drainage of particles to the sentinel right subiliac lymph node. The photoacoustic results revealed that the AuNRs' shapes are still stable regardless of their heterogeneous distributions inside the mammalian tumor and lymph nodes. Bioluminescence imaging was used to monitor metastasis using luciferin labeling techniques and has shown that AuNRs-PPTT inhibited metastasis completely within the first 21 days. Moreover, proteomics was run to determine the most pivotal inhibitory pathways: NETosis, cell growth, cell proliferation, inflammation, and extracellular matrix (ECM) degradation. These five mechanisms are interdependent within related networks, which synergistically explains the molecular mechanism of metastasis inhibition by AuNRs-PPTT. The current in vivo data ensures the viability of PPTT applications in inhibiting metastasis in humans.


Assuntos
Hipertermia Induzida , Nanopartículas Metálicas , Nanotubos , Neoplasias , Humanos , Animais , Camundongos , Ouro/química , Xenoenxertos , Terapia Fototérmica , Fototerapia/métodos , Hipertermia Induzida/métodos , Nanopartículas Metálicas/uso terapêutico , Neoplasias/terapia , Nanotubos/química , Linhagem Celular Tumoral , Mamíferos
6.
Proc Natl Acad Sci U S A ; 116(42): 20820-20827, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31570592

RESUMO

Polyphosphate fire retardants are a critical tactical resource for fighting fires in the wildland and in the wildland-urban interface. Yet, application of these retardants is limited to emergency suppression strategies because current formulations cannot retain fire retardants on target vegetation for extended periods of time through environmental exposure and weathering. New retardant formulations with persistent retention to target vegetation throughout the peak fire season would enable methodical, prophylactic treatment strategies of landscapes at high risk of wildfires through prolonged prevention of ignition and continual impediment to active flaming fronts. Here we develop a sprayable, environmentally benign viscoelastic fluid comprising biopolymers and colloidal silica to enhance adherence and retention of polyphosphate retardants on common wildfire-prone vegetation. These viscoelastic fluids exhibit appropriate wetting and rheological responses to enable robust retardant adherence to vegetation following spray application. Further, laboratory and pilot-scale burn studies establish that these materials drastically reduce ignition probability before and after simulated weathering events. Overall, these studies demonstrate how these materials actualize opportunities to shift the approach of retardant-based wildfire management from reactive suppression to proactive prevention at the source of ignitions.


Assuntos
Conservação dos Recursos Naturais/métodos , Retardadores de Chama/análise , Substâncias Viscoelásticas/química , Incêndios Florestais/prevenção & controle , Florestas , Polifosfatos/química , Estações do Ano , Árvores/química
7.
Circulation ; 141(7): 560-570, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32065769

RESUMO

BACKGROUND: Current exercise guidelines for clinical populations recommend an exercise therapy (ET) prescription of fixed intensity (moderate), duration (40-50 minutes per session), and volume (120-160 min/wk). A critical overarching element of exercise programming that has received minimal attention is dose scheduling. We investigated the tolerability and efficacy of 2 exercise training dose regimens on cardiorespiratory fitness and patient-reported outcomes in patients with posttreatment primary breast cancer. METHODS: Using a parallel-group randomized trial, we randomly allocated 174 postmenopausal patients (2.8 years after adjuvant therapy) with impaired peak oxygen consumption (VO2peak) to 1 of 2 supervised exercise training interventions delivered with a standard linear (LET) (fixed dose intensity per session for 160 min/wk) or nonlinear (NLET) (variable dose intensity per session for ≈120 min/wk) schedule compared with a stretching attention control group for 16 consecutive weeks. Stretching was matched to exercise dosing arms on the basis of location, frequency, duration, and treatment length. The primary end point was change in VO2peak (mL O2·kg-1·min-1) from baseline to after intervention. Secondary end points were patient-reported outcomes, tolerability, and safety. RESULTS: No serious adverse events were observed. Mean attendance was 64%, 75%, and 80% for attention control, LET, and NLET, respectively. In intention-to-treat analysis, VO2peak increased 0.6±1.7 mL O2·kg-1·min-1 (P=0.05) and 0.8±1.8 mL O2·kg-1·min-1 (P=0.07) in LET and NLET, respectively, compared with attention control. Change in VO2peak ranged from -2.7 to 4.1 mL O2·kg-1·min-1 and from -3.6 to 5.1 mL O2·kg-1·min-1 in LET and NLET, respectively. Approximately 40% of patients in both exercise dosing regimens were classified as VO2peak responders (ie, Δ ≥1.32 mL O2·kg-1·min-1). NLET improved all patient-reported outcomes compared with attention control. CONCLUSIONS: Short-term exercise training, independently of dosing schedule, is associated with modest improvements in cardiorespiratory fitness in patients previously treated for early-stage breast cancer. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01186367.


Assuntos
Neoplasias da Mama , Aptidão Cardiorrespiratória , Terapia por Exercício , Consumo de Oxigênio , Qualidade de Vida , Idoso , Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/terapia , Feminino , Humanos , Pessoa de Meia-Idade
8.
Breast Cancer Res Treat ; 185(3): 863-868, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33400034

RESUMO

PURPOSE: HER2-targeted therapies are associated with cardiotoxicity which is usually asymptomatic and reversible. We report the updated cardiac safety assessment of patients with compromised heart function receiving HER2-targeted therapy for breast cancer, enrolled in the SAFE-HEaRt trial, at a median follow-up of 3.5 years. METHODS: Thirty patients with stage I-IV HER2-positive breast cancer receiving trastuzumab with or without pertuzumab, or ado-trastuzumab emtansine (T-DM1), with asymptomatic LVEF (left ventricular ejection fraction) 40-49%, were started on cardioprotective medications, with the primary endpoint being completion of HER2-targeted therapy without cardiac events (CE) or protocol-defined asymptomatic worsening of LVEF. IRB-approved follow-up assessment included 23 patients. RESULTS: Median follow-up as of June 2020 is 42 months. The study met its primary endpoint with 27 patients (90%) completing their HER2-targeted therapies without cardiac issues. Of the 23 evaluable patients at long-term f/u, 14 had early stage breast cancer, and 9 had metastatic disease, 8 of whom remained on HER2-targeted therapies. One patient developed symptomatic heart failure with no change in LVEF. There were no cardiac deaths. The mean LVEF improved to 52.1% from 44.9% at study baseline, including patients who remained on HER2-targeted therapy, and those who received prior anthracyclines. CONCLUSIONS: Long-term follow-up of the SAFE-HEaRt study continues to provide safety data of HER2-targeted therapy use in patients with compromised heart function. The late development of cardiac dysfunction is uncommon and continued multi-disciplinary oncologic and cardiac care of patients is vital for improved patient outcomes.


Assuntos
Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Feminino , Seguimentos , Humanos , Receptor ErbB-2/genética , Volume Sistólico , Trastuzumab/efeitos adversos , Função Ventricular Esquerda
9.
Basic Res Cardiol ; 116(1): 19, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33742276

RESUMO

Endogenous capability of the post-mitotic human heart holds great promise to restore the injured myocardium. Recent evidence indicates that the extracellular vesicles (EVs) regulate cardiac homeostasis and regeneration. Here, we investigated the molecular mechanism of EVs for self-repair. We isolated EVs from human iPSC-derived cardiomyocytes (iCMs), which were exposed to hypoxic (hEVs) and normoxic conditions (nEVs), and examined their roles in in vitro and in vivo models of cardiac injury. hEV treatment significantly improved the viability of hypoxic iCMs in vitro and cardiac function of severely injured murine myocardium in vivo. Microarray analysis of the EVs revealed significantly enriched expression of the miR-106a-363 cluster (miR cluster) in hEVs vs. nEVs. This miR cluster preserved survival and contractility of hypoxia-injured iCMs and maintained murine left-ventricular (LV) chamber size, improved LV ejection fraction, and reduced myocardial fibrosis of the injured myocardium. RNA-Seq analysis identified Jag1-Notch3-Hes1 as a target intracellular pathway of the miR cluster. Moreover, the study found that the cell cycle activator and cytokinesis genes were significantly up-regulated in the iCMs treated with miR cluster and Notch3 siRNA. Together, these results suggested that the miR cluster in the EVs stimulated cardiomyocyte cell cycle re-entry by repressing Notch3 to induce cell proliferation and augment myocardial self-repair. The miR cluster may represent an effective therapeutic approach for ischemic cardiomyopathy.


Assuntos
Proliferação de Células , Vesículas Extracelulares/transplante , Células-Tronco Pluripotentes Induzidas/transplante , MicroRNAs/metabolismo , Infarto do Miocárdio/cirurgia , Miócitos Cardíacos/metabolismo , Receptor Notch3/metabolismo , Regeneração , Animais , Hipóxia Celular , Linhagem Celular , Modelos Animais de Doenças , Vesículas Extracelulares/metabolismo , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos SCID , MicroRNAs/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miócitos Cardíacos/patologia , Receptor Notch3/genética , Recuperação de Função Fisiológica , Transdução de Sinais , Função Ventricular Esquerda
10.
Environ Sci Technol ; 55(4): 2316-2323, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33529000

RESUMO

A preventative treatment of fire retardants at high-risk locales can potentially stop a majority of wildfires. For example, over 80% of wildfire ignitions in California occur at high-risk locales such as adjacent to roadsides and utility infrastructure. Recently a new class of ammonium polyphosphate retardants was developed with enhanced adherence and retention on vegetation to enable prophylactic treatments of these high-risk locals to provide season-long prevention of ignitions. Here, we compare three different ammonium (poly)phosphate-based wildland retardant formulations and evaluate their resistance to weathering and analyze their seasonal impact on soil chemistry following application onto grass. Soil samples from all three treatments demonstrated no changes in soil pH and total soil carbon and nitrogen amounts. Total soil phosphorus amounts increased by ∼2-3× following early precipitation, always remaining within typical topsoil amounts, and returned to the same level as control soil before spring. Available indices of ammonium, nitrate, and phosphate levels for all groups were elevated compared to the untreated control samples, again remaining within typical topsoil ranges across all time points and rainfall amounts evaluated. Microbial activity was decreased, potentially because the addition of available nutrients from retardant application reduced the need for organic decomposition. These results demonstrate that the application of ammonium (poly)phosphate-based retardants does not alter soil chemistry beyond typical topsoil compositions and are thus suitable for use in prophylactic wildfire prevention strategies.


Assuntos
Retardadores de Chama , Incêndios Florestais , Retardadores de Chama/análise , Nitrogênio/análise , Fosfatos , Estações do Ano , Solo
11.
Vet Dermatol ; 32(5): 467-e128, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34165828

RESUMO

BACKGROUND: Next-generation sequencing techniques have revealed that human and animal skin is colonised by a rich and diverse population of bacteria, and that microbial composition varies between different body sites and individuals. Very little is known about the normal microbiota of healthy equine skin. HYPOTHESIS/OBJECTIVES: To describe the taxonomic distributions of cutaneous bacterial microbiota in a population of healthy horses in Ontario, Canada, and to evaluate the effects of body site, individual and time of year on microbial diversity and community composition. ANIMALS: Samples were collected from four body sites (dorsum, ventral abdomen, pastern and groin) from 12 clinically healthy horses from the same farm. Samples were collected from all individuals at four time points (winter, spring, summer, autumn) within a calendar year. METHODS AND MATERIALS: Illumina sequencing of the V4 region of the 16S rRNA gene was performed following DNA extraction. Data were analysed using mothur software. RESULTS: Bacteria from 38 phyla and 1,665 genera were identified. Alpha diversity was higher in the winter and summer than spring and autumn although this was not statistically significant. Community membership and structure clustered more based on season than skin site. CONCLUSIONS AND CLINICAL IMPORTANCE: Healthy equine skin is inhabited by a marked diversity of microbiota. Individuals living in a similar environment share overlapping cutaneous microbial populations. These populations vary significantly over time and between body sites.


Assuntos
Microbiota , Animais , Bactérias/genética , DNA Bacteriano/genética , Cavalos , Estudos Longitudinais , RNA Ribossômico 16S/genética
12.
Opt Express ; 28(2): 1114-1123, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32121827

RESUMO

We report on magneto-optical resonances observed in sodium fluorescence from D2 manifold with an intensity-modulated light. Fluorescence resonances are measured in the perpendicular (90°) and backward (180°) directions to the light propagation in laboratory experiments using a sodium cell containing neon buffer gas. Properties of these resonances are studied by varying the magnetic field at fixed-light modulation frequency, and vice-versa. Modulation with low-duty cycle shows higher-harmonic resonances of the modulation frequency and sub-harmonic resonances of the Larmor frequency. A dark resonance with maximum amplitude for laser wavelength closer to the crossover peak is observed. The origin of this dark resonance observed in Na D2 line is discussed using a theoretical model. Present study is aimed towards improving the understanding of magneto-optical resonances for remote magnetometry applications with mesospheric sodium.

13.
Cytokine ; 127: 154974, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31978642

RESUMO

Although ischemic heart disease is the leading cause of death worldwide, mainstay treatments ultimately fail because they do not adequately address disease pathophysiology. Restoring the microvascular perfusion deficit remains a significant unmet need and may be addressed via delivery of pro-angiogenic cytokines. The therapeutic effect of cytokines can be enhanced by encapsulation within hydrogels, but current hydrogels do not offer sufficient clinical translatability due to unfavorable viscoelastic mechanical behavior which directly impacts the ability for minimally-invasive catheter delivery. In this report, we examine the therapeutic implications of dual-stage cytokine release from a novel, highly shear-thinning biocompatible catheter-deliverable hydrogel. We chose to encapsulate two protein-engineered cytokines, namely dimeric fragment of hepatocyte growth factor (HGFdf) and engineered stromal cell-derived factor 1α (ESA), which target distinct disease pathways. The controlled release of HGFdf and ESA from separate phases of the hyaluronic acid-based hydrogel allows extended and pronounced beneficial effects due to the precise timing of release. We evaluated the therapeutic efficacy of this treatment strategy in a small animal model of myocardial ischemia and observed a significant benefit in biological and functional parameters. Given the encouraging results from the small animal experiment, we translated this treatment to a large animal preclinical model and observed a reduction in scar size, indicating this strategy could serve as a potential adjunct therapy for the millions of people suffering from ischemic heart disease.


Assuntos
Hidrogéis/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Catéteres , Células Cultivadas , Modelos Animais de Doenças , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Ácido Hialurônico/administração & dosagem , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/metabolismo , Miocárdio/patologia , Ratos
14.
Opt Lett ; 45(22): 6230-6233, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33186957

RESUMO

A beam shaping approach has been implemented to realize high-performance waveguide crossings based on cosine tapers. Devices with a compact footprint of 4.7µm×4.7µm were fabricated on the GLOBALFOUNDRIES 45 nm monolithic silicon photonics platform (45 CLO technology). Fabricated devices are found to be nearly wavelength independent (±0.035dB for 1260nm≤λ≤1360nm) with low insertion loss (∼0.2dB) and crosstalk (-35dB). The measured response of the devices is consistent with the three-dimensional finite-difference time-domain simulation results. The design stability is validated by measuring the device insertion loss on eight chips, which is found to be 0.197±0.017dB at the designed center wavelength of 1310 nm.

15.
Biomacromolecules ; 21(9): 3704-3712, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32816460

RESUMO

Cancer immunotherapy can be augmented with toll-like receptor agonist (TLRa) adjuvants, which interact with immune cells to elicit potent immune activation. Despite their potential, use of many TLRa compounds has been limited clinically due to their extreme potency and lack of pharmacokinetic control, causing systemic toxicity from unregulated systemic cytokine release. Herein, we overcome these shortcomings by generating poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) nanoparticles (NPs) presenting potent TLR7/8a moieties on their surface. The NP platform allows precise control of TLR7/8a valency and resulting surface presentation through self-assembly using nanoprecipitation. We hypothesize that the pharmacokinetic profile of the NPs minimizes systemic toxicity, localizing TLR7/8a presentation to the tumor bed and tumor-draining lymph nodes. In conjunction with antiprogrammed death-ligand 1 (anti-PD-L1) checkpoint blockade, peritumoral injection of TLR7/8a NPs slows tumor growth, extends survival, and decreases systemic toxicity in comparison to the free TLR7/8a in a murine colon adenocarcinoma model. These NPs constitute a modular platform for controlling pharmacokinetics of immunostimulatory molecules, resulting in increased potency and decreased toxicity.


Assuntos
Nanopartículas , Neoplasias , Animais , Antígeno B7-H1 , Imunoterapia , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/tratamento farmacológico , Receptor 7 Toll-Like
16.
Breast Cancer Res Treat ; 175(1): 239-246, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30721443

RESUMO

PURPOSE: Asymptomatic decline in left ventricular ejection fraction (LVEF) or heart failure (HF) occurs in up to 25% of patients treated with trastuzumab and can result in incomplete breast cancer therapy. The cardiac safety of continuing trastuzumab in patients with asymptomatic LVEF decline is unknown. We report the cardiac outcomes of patients treated with trastuzumab after a significant asymptomatic LVEF decline. METHODS: Patients with HER2-positive breast cancer and asymptomatic LVEF decline to < 50% during trastuzumab were identified from an institutional echocardiogram database. Patients who received trastuzumab with a LVEF < 50% were classified as the continued group, whereas patients who had trastuzumab held until LVEF improved to ≥ 50% or who had trastuzumab permanently discontinued were classified as the interrupted group. Cardiac events were defined as HF (New York Heart Association class III-IV) or cardiovascular death. RESULTS: Sixty patients were included; the median age was 54 years. In 23 patients who continued trastuzumab, 14 (61%) tolerated trastuzumab without a cardiac event, 6 (26%) developed worsening LVEF (range 25-42%) leading to trastuzumab discontinuation, and three (13%) developed a cardiac event (1 HF, 2 possible/probable cardiovascular deaths). In 37 patients with interrupted trastuzumab, 15 (41%) were re-challenged with trastuzumab after LVEF improved to > 50%, 21 (57%) were not re-challenged, and one (3%) developed HF. More patients in the continued trastuzumab group had metastatic disease (39% vs. 5%, p = 0.002). The final LVEF after median follow-up of 633 days was similar between patients with trastuzumab continuation versus interruption (54% vs. 56%, p = 0.29). CONCLUSION: Continuation of trastuzumab after an asymptomatic LVEF decline to < 50% in patients who are expected to benefit from additional anti-HER2 therapy is a promising approach that warrants further investigation.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Neoplasias da Mama/complicações , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Volume Sistólico , Trastuzumab/efeitos adversos , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Cardiotoxicidade , Ecocardiografia , Feminino , Cardiopatias/diagnóstico , Humanos , Pessoa de Meia-Idade , Terapia de Alvo Molecular/efeitos adversos , Gradação de Tumores , Estadiamento de Neoplasias , Receptor ErbB-2/antagonistas & inibidores , Fatores de Risco , Trastuzumab/uso terapêutico
17.
Curr Opin Cardiol ; 34(4): 451-458, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31082851

RESUMO

PURPOSE OF REVIEW: Cardiotoxicity is a well recognized adverse effect of human epidermal growth factor receptor 2 (HER2)-targeted therapies. The goal of this review is to highlight recent studies that have advanced our knowledge of the diagnosis, prevention, and management of cardiotoxicity associated with HER2-targeted agents. RECENT FINDINGS: Several clinical risk factors for cardiotoxicity associated with HER2-targeted therapies have been identified including age, low-baseline left ventricular ejection fraction, and treatment with anthracyclines; however, these remain insufficient to identify all patients at risk for cardiotoxicity. Routine cardiac monitoring remains the standard for cardiotoxicity surveillance, although the optimal frequency and modality of monitoring remains uncertain. Global longitudinal strain, T1/T2 weighted CMR imaging protocols, and circulating biomarkers can detect early signs of cardiotoxicity, but studies are needed to investigate whether use of these markers in clinical practice improves patient outcomes. Cardioprotective medications (e.g. beta-blockers or ACE-inhibitors) may be of benefit to patients at increased risk for cardiotoxicity from HER2-taregeted therapies, particularly those who are treated with an anthracycline-containing regimen. SUMMARY: Improved risk stratification of patients during HER2-targeted therapy and effective prevention and management strategies for cardiotoxicity are needed to enhance the value of longitudinal cardiac monitoring and increase cardiac safety so that optimal breast cancer treatment can be delivered.


Assuntos
Neoplasias da Mama , Antraciclinas , Antineoplásicos , Cardiotoxicidade , Humanos , Terapia de Alvo Molecular , Receptor ErbB-2
18.
Curr Treat Options Oncol ; 20(6): 51, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31073788

RESUMO

OPINION STATEMENT: Treatment-related cardiotoxicity remains a significant concern for breast cancer patients undergoing cancer treatment and extends into the survivorship period, with adverse cardiovascular (CV) outcomes further compounded by the presence of pre-existing CV disease or traditional CV risk factors. Awareness of the cardiotoxicity profiles of contemporary breast cancer treatments and optimization of CV risk factors are crucial in mitigating cardiotoxicity risk. Assessment of patient- and treatment-specific risk with appropriate CV surveillance is another key component of care. Mismatch between baseline cardiotoxicity risk and intensity of cardiotoxicity surveillance can lead to unnecessary downstream testing, increased healthcare expenditure, and interruption or discontinuation of potentially life-saving treatment. Efforts to identify early imaging and/or circulating biomarkers of cardiotoxicity and develop effective management strategies are needed to optimize the CV and cancer outcomes of breast cancer survivors.


Assuntos
Neoplasias da Mama/complicações , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/etiologia , Antraciclinas/efeitos adversos , Antraciclinas/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores , Neoplasias da Mama/terapia , Cardiotoxicidade/prevenção & controle , Cardiotoxicidade/terapia , Gerenciamento Clínico , Feminino , Humanos , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Radioterapia/efeitos adversos , Radioterapia/métodos
19.
Proc Natl Acad Sci U S A ; 113(50): 14255-14260, 2016 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-27911849

RESUMO

Hydrogels are a class of soft material that is exploited in many, often completely disparate, industrial applications, on account of their unique and tunable properties. Advances in soft material design are yielding next-generation moldable hydrogels that address engineering criteria in several industrial settings such as complex viscosity modifiers, hydraulic or injection fluids, and sprayable carriers. Industrial implementation of these viscoelastic materials requires extreme volumes of material, upwards of several hundred million gallons per year. Here, we demonstrate a paradigm for the scalable fabrication of self-assembled moldable hydrogels using rationally engineered, biomimetic polymer-nanoparticle interactions. Cellulose derivatives are linked together by selective adsorption to silica nanoparticles via dynamic and multivalent interactions. We show that the self-assembly process for gel formation is easily scaled in a linear fashion from 0.5 mL to over 15 L without alteration of the mechanical properties of the resultant materials. The facile and scalable preparation of these materials leveraging self-assembly of inexpensive, renewable, and environmentally benign starting materials, coupled with the tunability of their properties, make them amenable to a range of industrial applications. In particular, we demonstrate their utility as injectable materials for pipeline maintenance and product recovery in industrial food manufacturing as well as their use as sprayable carriers for robust application of fire retardants in preventing wildland fires.

20.
Can Vet J ; 60(3): 268-274, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30872849

RESUMO

Canine food allergies are the result of an immune-mediated hypersensitivity reaction to dietary proteins and can manifest as a variety of dermatologic and/or gastrointestinal clinical signs. Food elimination trials followed by provocation tests are used to diagnose food allergies; however, no research has been conducted to determine whether elimination trials and provocation tests are being properly implemented by pet owners. The objectives of this study were to determine the level of knowledge of dog owners regarding food allergies, and to investigate how dog owners approach diagnosis and treatment with their veterinarians. This information will provide veterinary teams with insight on how to work with dog owners to obtain successful diagnosis and treatment. The results indicate that appropriate diet selection for the food elimination trial, owner education on compliance during the trial, and re-challenging with the previous diet should be the focal points for veterinarians suspecting food allergies in a canine patient.


Évaluation des connaissances des propriétaires de chiens portant sur le diagnostic et le traitement des allergies alimentaires canines. Les allergies alimentaires canines sont le résultat d'une réaction d'hypersensibilité à médiation immunitaire face aux protéines alimentaires et elles peuvent se manifester par divers signes cliniques dermatologiques et/ou gastro-intestinaux. Les essais d'élimination d'aliments suivis de tests de provocation sont utilisés pour diagnostiquer les allergies alimentaires. Cependant, aucune recherche n'a été réalisée pour déterminer si les essais d'élimination et les tests de provocation sont mis en place de façon adéquate par les propriétaires. Les objectifs de cette étude étaient de déterminer le niveau de connaissances des propriétaires de chiens concernant les allergies alimentaires et d'étudier la façon dont les propriétaires de chiens envisagent le diagnostic et le traitement avec leur médecin vétérinaire. Ces renseignements permettront aux équipes vétérinaires de constater comment travailler avec les propriétaires de chiens afin d'obtenir un diagnostic et un traitement réussi. Les résultats indiquent que le bon choix d'alimentation pour les essais d'élimination des aliments, l'éducation des propriétaires pour la conformité durant les essais et de nouveaux tests avec l'alimentation antérieure devraient être les principaux sujets pour les médecins vétérinaires soupçonnant des allergies alimentaires chez un patient canin.(Traduit par Isabelle Vallières).


Assuntos
Doenças do Cão , Hipersensibilidade Alimentar/veterinária , Médicos Veterinários , Animais , Cães , Humanos , Inquéritos e Questionários
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