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1.
Immunol Invest ; 53(4): 586-603, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38700235

RESUMEN

BACKGROUND: Acute myocardial infarction (AMI) is one of the principal causes of death in Mexico and worldwide. AMI triggers an acute inflammatory process that induces the activation of different populations of the innate immune system. Innate lymphoid cells (ILCs) are an innate immunity, highly pleiotropic population, which have been observed to participate in tissue repair and polarization of the adaptive immune response. OBJECTIVE: We aimed to analyze the levels of subsets of ILCs in patients with ST-segment elevation myocardial infarction (STEMI), immediately 3 and 6 months post-AMI, and analyze their correlation with clinical parameters. RESULTS: We evaluated 29 STEMI patients and 15 healthy controls and analyzed the different subsets of circulating ILCs, immediately 3 and 6 months post-AMI. We observed higher levels of circulating ILCs in STEMI patients compared to control subjects and a significant correlation between ILC levels and cardiac function. We also found increased production of the cytokines interleukin 5 (IL-5) and interleukin 17A (IL-17A), produced by ILC2 cells and by ILC3 cells, respectively, in the STEMI patients. CONCLUSION: This study shows new evidence of the role of ILCs in the pathophysiology of AMI and their possible involvement in the maintenance of cardiac function.


Asunto(s)
Inmunidad Innata , Linfocitos , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/inmunología , Masculino , Femenino , Persona de Mediana Edad , Linfocitos/inmunología , Anciano , Interleucina-17/metabolismo , Interleucina-5 , Citocinas/metabolismo , Estudios de Casos y Controles
2.
Oncologist ; 28(6): 542-550, 2023 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-36848260

RESUMEN

BACKGROUND: Establishing care preferences and selecting a prepared medical decision-maker (MDM) are basic components of advance care planning (ACP) and integral to treatment planning. Systematic ACP in the cancer setting is uncommon. We evaluated a systematic social work (SW)-driven process for patient selection of a prepared MDM. METHODS: We used a pre/post design, centered on SW counseling incorporated into standard-of-care practice. New patients with gynecologic malignancies were eligible if they had an available family caregiver or an established Medical Power of Attorney (MPOA). Questionnaires were completed at baseline and 3 months to ascertain MPOA document (MPOAD) completion status (primary objective) and evaluate factors associated with MPOAD completion (secondary objectives). RESULTS: Three hundred and sixty patient/caregiver dyads consented to participate. One hundred and sixteen (32%) had MPOADs at baseline. Twenty (8%) of the remaining 244 dyads completed MPOADs by 3 months. Two hundred and thirty-six patients completed the values and goals survey at both baseline and follow-up: at follow-up, care preferences were stable in 127 patients (54%), changed toward more aggressive care in 60 (25%), and toward the focus on the quality of life in 49 (21%). Correlation between the patient's values and goals and their caregiver's/MPOA's perception was very weak at baseline, improving to moderate at follow-up. Patients with MPOADs by study completion had statistically significant higher ACP Engagement scores than those without. CONCLUSION: A systematic SW-driven intervention did not engage new patients with gynecologic cancers to select and prepare MDMs. Change in care preferences was common, with caregivers' knowledge of patients' treatment preferences moderate at best.


Asunto(s)
Planificación Anticipada de Atención , Neoplasias de los Genitales Femeninos , Humanos , Femenino , Participación del Paciente , Calidad de Vida , Directivas Anticipadas , Neoplasias de los Genitales Femeninos/terapia
3.
Planta ; 259(2): 32, 2023 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-38153530

RESUMEN

MAIN CONCLUSION: CRISPR/Cas technology has greatly facilitated plant non-coding RNA (ncRNA) biology research, establishing itself as a promising tool for ncRNA functional characterization and ncRNA-mediated plant improvement. Throughout the last decade, the promising genome editing tool clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated proteins (Cas; CRISPR/Cas) has allowed unprecedented advances in the field of plant functional genomics and crop improvement. Even though CRISPR/Cas-mediated genome editing system has been widely used to elucidate the biological significance of a number of plant protein-coding genes, this technology has been barely applied in the functional analysis of those non-coding RNAs (ncRNAs) that modulate gene expression, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Nevertheless, compelling findings indicate that CRISPR/Cas-based ncRNA editing has remarkable potential for deciphering the biological roles of ncRNAs in plants, as well as for plant breeding. For instance, it has been demonstrated that CRISPR/Cas tool could overcome the challenges associated with other approaches employed in functional genomic studies (e.g., incomplete knockdown and off-target activity). Thus, in this review article, we discuss the current status and progress of CRISPR/Cas-mediated ncRNA editing in plant science in order to provide novel prospects for further assessment and validation of the biological activities of plant ncRNAs and to enhance the development of ncRNA-centered protocols for crop improvement.


Asunto(s)
MicroARNs , ARN Largo no Codificante , ARN Largo no Codificante/genética , MicroARNs/genética , Sistemas CRISPR-Cas/genética , ARN no Traducido/genética , Genómica
4.
Appl Math Model ; 121: 506-523, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37234701

RESUMEN

A new contagious disease or unidentified COVID-19 variants could provoke a new collapse in the global economy. Under such conditions, companies, factories, and organizations must adopt reopening policies that allow their operations to reduce economic effects. Effective reopening policies should be designed using mathematical models that emulate infection chains through individual interactions. In contrast to other modeling approaches, agent-based schemes represent a computational paradigm used to characterize the person-to-person interactions of individuals inside a system, providing accurate simulation results. To evaluate the optimal conditions for a reopening policy, authorities and decision-makers need to conduct an extensive number of simulations manually, with a high possibility of losing information and important details. For this reason, the integration of optimization and simulation of reopening policies could automatically find the realistic scenario under which the lowest risk of infection was attained. In this paper, the metaheuristic technique of the Whale Optimization Algorithm is used to find the solution with the minimal transmission risk produced by an agent-based model that emulates a hypothetical re-opening context. Our scheme finds the optimal results of different generical activation scenarios. The experimental results indicate that our approach delivers practical knowledge and essential estimations for identifying optimal re-opening strategies with the lowest transmission risk.

5.
Biophys J ; 121(23): 4600-4614, 2022 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-36273263

RESUMEN

Cell shape change processes, such as proliferation, polarization, migration, and cancer metastasis, rely on a dynamic network of macromolecules. The proper function of this network enables mechanosensation, the ability of cells to sense and respond to mechanical cues. Myosin II and cortexillin I, critical elements of the cellular mechanosensory machinery, preassemble in the cytoplasm of Dictyostelium cells into complexes that we have termed contractility kits (CKs). Two IQGAP proteins then differentially regulate the mechanoresponsiveness of the cortexillin I-myosin II elements within CKs. To investigate the mechanism of CK self-assembly and gain insight into possible molecular means for IQGAP regulation, we developed a coarse-grained excluded volume molecular model in which all protein polymers are represented by nm-sized spheres connected by spring-like links. The model is parameterized using experimentally measured parameters acquired through fluorescence cross-correlation spectroscopy and fluorescence correlation spectroscopy, which describe the interaction affinities and diffusion coefficients for individual molecular components, and which have also been validated via several orthogonal methods. Simulations of wild-type and null-mutant conditions implied that the temporal order of assembly of these kits is dominated by myosin II dimer formation and that IQGAP proteins mediate cluster growth. In addition, our simulations predicted the existence of "ambiguous" CKs that incorporate both classes of IQGAPs, and we confirmed this experimentally using fluorescence cross-correlation spectroscopy. The model serves to describe the formation of the CKs and how their assembly enables and regulates mechanosensation at the molecular level.


Asunto(s)
Dictyostelium
6.
Sensors (Basel) ; 21(4)2021 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-33567489

RESUMEN

Wireless Sensor Networks constitute an important part of the Internet of Things, and in a similar way to other wireless technologies, seek competitiveness concerning savings in energy consumption and information availability. These devices (sensors) are typically battery operated and distributed throughout a scenario of particular interest. However, they are prone to interference attacks which we know as jamming. The detection of anomalous behavior in the network is a subject of study where the routing protocol and the nodes increase power consumption, which is detrimental to the network's performance. In this work, a simple jamming detection algorithm is proposed based on an exhaustive study of performance metrics related to the routing protocol and a significant impact on node energy. With this approach, the proposed algorithm detects areas of affected nodes with minimal energy expenditure. Detection is evaluated for four known cluster-based protocols: PEGASIS, TEEN, LEACH, and HPAR. The experiments analyze the protocols' performance through the metrics chosen for a jamming detection algorithm. Finally, we conducted real experimentation with the best performing wireless protocols currently used, such as Zigbee and LoRa.

7.
Haematologica ; 105(7): 1907-1913, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31601688

RESUMEN

The impact of pre-treatment maximum standardized uptake value (SUVmax) on the outcome of follicular lymphoma (FL) following specific frontline regimens has not been explored. We performed a retrospective analysis of 346 patients with advanced stage follicular lymphoma (FL) without histological evidence of transformation, and analyzed the impact of SUVmax on outcome after frontline therapy. Fifty-two (15%) patients had a SUVmax >18, and a large lymph node ≥6 cm was the only factor associating with SUVmax >18 on multivariate analysis (odds ratio 2.7, 95% confidence interval [CI]: 1.3-5.3, P=0.006). The complete response rate was significantly lower among patients treated with non-anthracycline-based regimens if SUVmax was >18 (45% vs 92%, P<0.001), but not among patients treated with R-CHOP (P=1). SUVmax >18 was associated with significantly shorter progression-free survival among patients treated with non-anthracycline-based regimens (77 months vs. not reached, P=0.02), but not among patients treated with R-CHOP (P=0.73). SUVmax >18 associated with shorter overall survival (OS) both in patients treated with R-CHOP (8-year OS 70% vs. 90%, P=0.02) and non-anthracycline-based frontline regimens (8-year OS 50% vs 85%, P=0.001). In conclusion, pre-treatment PET scan has prognostic and predictive value in patients with advanced stage FL receiving frontline treatment.


Asunto(s)
Fluorodesoxiglucosa F18 , Linfoma Folicular , Humanos , Ganglios Linfáticos , Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamiento farmacológico , Tomografía de Emisión de Positrones , Pronóstico , Estudios Retrospectivos
8.
Br J Haematol ; 175(2): 290-299, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27448187

RESUMEN

There are limited reports that baseline peripheral absolute neutrophil count (ANC), absolute monocyte count (AMC), absolute lymphocyte count (ALC) and serum ß2-microglobulin level independently predict survival in patients with diffuse large B-cell lymphoma (DLBCL). To confirm these findings, we analysed these parameters together with components of the International Prognostic Index (IPI) in patients with newly-diagnosed DLBCL. We evaluated baseline clinical features for their ability to predict survival in 817 newly diagnosed, previously untreated patients with DLBCL who received frontline treatments between October 2001 and December 2011. The median age at diagnosis was 58 years. Multivariate analysis identified elevated baseline ANC (P = 0·036), AMC (P = 0·028) and serum ß2-microglobulin level (P < 0·001), poor performance status (P < 0·001) and high number of extranodal disease sites (P = 0·0497) as independent unfavourable predictors of OS; serum ß2-microglobulin level was the strongest predictor of survival outcomes among all the parameters. High baseline serum ß2-microglobulin, ANC and AMC levels are independent prognostic factors for short overall survival in patients with newly diagnosed DLBCL. Our new model, based on the above five parameters, better stratifies patients into various risk categories than the IPI for newly diagnosed DLBCL.


Asunto(s)
Recuento de Leucocitos , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/mortalidad , Monocitos , Neutrófilos , Microglobulina beta-2/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/diagnóstico , Masculino , Persona de Mediana Edad , Monocitos/patología , Análisis Multivariante , Estadificación de Neoplasias , Neutrófilos/patología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Adulto Joven
9.
Psychooncology ; 24(2): 138-46, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24831084

RESUMEN

OBJECTIVES: Life-threatening diseases such as cancer represent unique traumas-compared with singular, time-limited traumatic events-given their multidimensional, uncertain, and continuing nature. However, few studies have examined the impact of cancer on patients as a persistent stressor. The aim of this qualitative study is to explore patients' ongoing experiences of living with cancer and the changes encountered in this experience over time. METHODS: Written reflections to three open-ended questions collected from 28 patients on their experience of cancer at two time points were analyzed to explore participants' experiences and perspectives over time. Content analysis using a framework approach was employed to code, categorize, and summarize data into a thematic framework. RESULTS: Data analysis yielded the thematic framework-living with paradox, consisting of four interrelated themes: sources, experiences, resolution of paradox, and challenges with medical culture/treatment. The primary theme concerned moving through a dualistic and complex cancer experience of concurrently negative and positive emotional states across the course of cancer. CONCLUSIONS: Respondents indicated that cycling through this contradictory trajectory was neither linear, nor singular, nor conclusive in nature, but reiterative across time. Recognition that patients' cancer experience may be paradoxical and tumultuous throughout the cancer trajectory can influence how practitioners provide patients with needed support during diagnosis, treatment, and recovery. This also has implications for interventions, treatment, and care plans, and adequately responding to the diversity of patient's psychosocial, physical, existential, and spiritual experience of illness.


Asunto(s)
Linfoma/psicología , Estrés Psicológico/psicología , Adulto , Anciano , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Adulto Joven
10.
Sensors (Basel) ; 14(12): 23581-23619, 2014 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-25494353

RESUMEN

In this paper we describe a novel proposal in the field of smart cities: using an ontology matching algorithm to guarantee the automatic information exchange between the agents and the smart city. A smart city is composed by different types of agents that behave as producers and/or consumers of the information in the smart city. In our proposal, the data from the context is obtained by sensor and device agents while users interact with the smart city by means of user or system agents. The knowledge of each agent, as well as the smart city's knowledge, is semantically represented using different ontologies. To have an open city, that is fully accessible to any agent and therefore to provide enhanced services to the users, there is the need to ensure a seamless communication between agents and the city, regardless of their inner knowledge representations, i.e., ontologies. To meet this goal we use ontology matching techniques, specifically we have defined a new ontology matching algorithm called OntoPhil to be deployed within a smart city, which has never been done before. OntoPhil was tested on the benchmarks provided by the well known evaluation initiative, Ontology Alignment Evaluation Initiative, and also compared to other matching algorithms, although these algorithms were not specifically designed for smart cities. Additionally, specific tests involving a smart city's ontology and different types of agents were conducted to validate the usefulness of OntoPhil in the smart city environment.

11.
J Environ Manage ; 114: 225-31, 2013 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-23146335

RESUMEN

Different activated carbons modified with iron hydro(oxide) nanoparticles were tested for their ability to adsorb arsenic from water. Adsorption isotherms were determined at As (V) concentrations < 1 ppm, with varying pH (6, 7, 8) and temperature (25 and 35 °C). Also, competition effect of anions on the As (V) adsorption capacity was evaluated using groundwater. The surface areas of the modified activated carbons ranged from 632 m(2) g(-1) to 1101 m(2) g(-1), and their maximum arsenic adsorption capacity varied from 370 µg g(-1) to 1250 µg g(-1). Temperature had no significant effect on arsenic adsorption; however, arsenic adsorption decreased 32% when the solution pH increased from 6 to 8. In addition, when groundwater was used in the experiments, the arsenic adsorption considerably decreased due to the presence of competing anions (mainly SO(4)(2-), Cl(-) and F(-)) for active sites. The data from kinetic studies fitted well to the pseudo-second-order model (r(2) = 0.98-0.99). The results indicated that sample CAZ-M had faster kinetics than the other two materials in the first 10 min. However, sample F400-M was only 5.5% slower than CAZ-M. The results of this study show that iron modified activated carbons are efficient adsorbents for arsenic at concentrations lower than 300 µg L(-1).


Asunto(s)
Arsénico/aislamiento & purificación , Carbón Orgánico/química , Compuestos Férricos/química , Nanopartículas del Metal/química , Contaminantes Químicos del Agua/aislamiento & purificación , Adsorción , Concentración de Iones de Hidrógeno , Cinética , Modelos Químicos , Temperatura , Termodinámica
12.
Pharmaceutics ; 15(2)2023 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-36840033

RESUMEN

Neurodegenerative diseases (NDDs) are characterized by the progressive degeneration and/or loss of neurons belonging to the central nervous system, and represent one of the major global health issues. Therefore, a number of immunotherapeutic approaches targeting the non-functional or toxic proteins that induce neurodegeneration in NDDs have been designed in the last decades. In this context, due to unprecedented advances in genetic engineering techniques and molecular farming technology, pioneering plant-based immunogenic antigen expression systems have been developed aiming to offer reliable alternatives to deal with important NDDs, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Diverse reports have evidenced that plant-made vaccines trigger significant immune responses in model animals, supported by the production of antibodies against the aberrant proteins expressed in the aforementioned NDDs. Moreover, these immunogenic tools have various advantages that make them a viable alternative for preventing and treating NDDs, such as high scalability, no risk of contamination with human pathogens, cold chain free production, and lower production costs. Hence, this article presents an overview of the current progress on plant-manufactured vaccines for NDDs and discusses its future prospects.

13.
Theranostics ; 13(1): 1-15, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36593949

RESUMEN

Background: Immune-modulating therapies impart positive outcomes in a subpopulation of cancer patients. Improved delivery strategies and non-invasive monitoring of anti-tumor effects can help enhance those outcomes and understand the mechanisms associated with the generation of anti-tumor immune responses following immunotherapy. Methods: We report on the design of a microneedle (MN) platform capable of simultaneous delivery of immune activators and collection of interstitial skin fluid (ISF) to monitor therapeutic responses. While either approach has shown promise, the integration of the therapy and diagnostic arms into one MN platform has hardly been explored before. MNs were synthesized out of crosslinked hyaluronic acid (HA) and loaded with a model immunomodulatory nanoparticle-containing drug, CpG oligodinucleotides (TLR9 agonist), for cancer therapy in melanoma and colon cancer models. The therapeutic response was monitored by longitudinal analysis of entrapped immune cells in the MNs following patch retrieval and digestion. Results: Transdermal delivery of CpG-containing NPs with MNs induced anti-tumor immune responses in multiple syngeneic mouse cancer models. CpG-loaded MNs stimulated innate immune cells and reduced tumor growth. Intravital microscopy showed deposition and spatiotemporal co-localization of CpG-NPs within the tumor microenvironment when delivered with MNs. Analysis of MN-sampled ISF revealed similar immune signatures to those seen in the bulk tumor homogenate, such as increased populations of macrophages and effector T cells following treatment. Conclusions: Our hydrogel-based MNs enable effective transdermal drug delivery into immune cells in the tumor microenvironment, and upon retrieval, enable studying the immune response to the therapy over time. This platform has the theranostic potential to deliver a range of combination therapies while detecting biomarkers.


Asunto(s)
Agentes Inmunomoduladores , Neoplasias , Animales , Ratones , Sistemas de Liberación de Medicamentos , Piel , Administración Cutánea , Polímeros/farmacología , Microambiente Tumoral
14.
Front Bioeng Biotechnol ; 11: 1208547, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37576994

RESUMEN

MicroRNAs (miRNAs) are short (18-25 nt), non-coding, widely conserved RNA molecules responsible for regulating gene expression via sequence-specific post-transcriptional mechanisms. Since the human miRNA transcriptome regulates the expression of a number of tumor suppressors and oncogenes, its dysregulation is associated with the clinical onset of different types of cancer. Despite the fact that numerous therapeutic approaches have been designed in recent years to treat cancer, the complexity of the disease manifested by each patient has prevented the development of a highly effective disease management strategy. However, over the past decade, artificial miRNAs (i.e., anti-miRNAs and miRNA mimics) have shown promising results against various cancer types; nevertheless, their targeted delivery could be challenging. Notably, numerous reports have shown that nanotechnology-based delivery of miRNAs can greatly contribute to hindering cancer initiation and development processes, representing an innovative disease-modifying strategy against cancer. Hence, in this review, we evaluate recently developed nanotechnology-based miRNA drug delivery systems for cancer therapeutics and discuss the potential challenges and future directions, such as the promising use of plant-made nanoparticles, phytochemical-mediated modulation of miRNAs, and nanozymes.

15.
J Cancer Surviv ; 2023 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-36952212

RESUMEN

PURPOSE: We conducted a systematic review and meta-analysis to determine the use of e-cigarettes among cancer survivors, factors associated with their use, and prevalence of e-cigarette use as a quit attempt. METHODS: We searched five electronic databases until June 2022. Two authors independently selected studies, appraised their quality, and collected data. RESULTS: Twenty-three publications from eight data sources (national surveys) met our eligibility criteria. The pooled rate of lifetime e-cigarette use among cancer survivors was 15% (95% CI 6-27%); current use was 3% (95% CI 0-8%). Among survivors who currently used traditional cigarettes, 63% (95% CI 57-69%) also used e-cigarettes. The reported rates of weighted lifetime e-cigarette use differed between age groups (18-44 years, up to 46.7%; 45-64, up to 27.2%; ≥65, up to 24.8%). Nine publications reported factors associated with lifetime e-cigarette use (i.e., active use of traditional cigarettes; heavy drinking; poor mental health; younger age; being male, non-Hispanic White, or single; having less than high school education or income ≤$25,000 USD; and living in the South regions of the US or urban areas). E-cigarettes were used as a quit resource by 75% of survivors reporting dual use of electronic and traditional cigarettes (95% CI 63%, 85%). CONCLUSION: More than two-thirds of survivors currently using traditional cigarettes also use e-cigarettes. Higher use rates of e-cigarettes were reported among young cancer survivors compared to older survivors. Future studies are needed to assess the impact of e-cigarettes on long-term health and improve screening of smoking behaviors. IMPLICATIONS FOR CANCER SURVIVORS: Our study provides an overview of the prevalence of e-cigarette use and sociodemographic risk factors associated with e-cigarette use among cancer survivors. The findings can assist providers in supporting attempts to quit among cancer survivors.

16.
Nat Nanotechnol ; 18(11): 1351-1363, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37443252

RESUMEN

Intravenously administered cyclic dinucleotides and other STING agonists are hampered by low cellular uptake and poor circulatory half-life. Here we report the covalent conjugation of cyclic dinucleotides to poly(ß-amino ester) nanoparticles through a cathepsin-sensitive linker. This is shown to increase stability and loading, thereby expanding the therapeutic window in multiple syngeneic tumour models, enabling the study of how the long-term fate of the nanoparticles affects the immune response. In a melanoma mouse model, primary tumour clearance depends on the STING signalling by host cells-rather than cancer cells-and immune memory depends on the spleen. The cancer cells act as a depot for the nanoparticles, releasing them over time to activate nearby immune cells to control tumour growth. Collectively, this work highlights the importance of nanoparticle structure and nano-biointeractions in controlling immunotherapy efficacy.


Asunto(s)
Melanoma , Nanopartículas , Neoplasias , Animales , Ratones , Polímeros/farmacología , Neoplasias/tratamiento farmacológico , Transducción de Señal , Nanopartículas/uso terapéutico , Nanopartículas/química
17.
J Clin Oncol ; 41(4): 745-755, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-35952327

RESUMEN

PURPOSE: Chemoimmunotherapy for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) is largely unchanged for decades. Both preclinical models and clinical data suggest the combination of lenalidomide and ibrutinib may have synergy in DLBCL, particularly in the non-germinal center B-cell-like subset. METHODS: We enrolled 60 patients with newly diagnosed non-germinal center B-cell-like DLBCL in this investigator-initiated, single-arm phase II trial of rituximab, lenalidomide, and ibrutinib (RLI) with the sequential addition of chemotherapy (ClinicalTrials.gov identifier: NCT02636322). Patients were treated with rituximab 375 mg/m2 intravenous once on day 1, lenalidomide 25 mg once per day on days 1-10, and ibrutinib 560 mg once daily continuously of each 21-day cycle (RLI). After two cycles, standard chemotherapy was added to RLI for six additional cycles. The primary end points were overall response rate (ORR) after two cycles of RLI alone and complete response rate after completion of RLI with chemotherapy. In evaluable samples, circulating tumor DNA and DLBCL90 assays were performed. RESULTS: The median age was 63.5 years (range, 29-83 years) with 28% age 70 years or older. The revised international prognostic index identified 42% as high risk, and 62% were double expressor of MYC and BCL2 protein. The ORR after two cycles of RLI was 86.2%, and the complete response rate at the end of RLI-chemotherapy was 94.5%. With a median follow-up of 31 months, the progression-free survival and overall survival were at 91.3% and 96.6% at 2 years, respectively. CONCLUSION: Smart Start is the first study, to our knowledge, to treat newly diagnosed DLBCL with a targeted therapy combination before chemotherapy. RLI produced a high ORR, and RLI with chemotherapy resulted in durable responses. This establishes the potential for developing biologically driven and noncytotoxic first-line therapies for DLBCL.


Asunto(s)
Linfoma de Células B Grandes Difuso , Piperidinas , Humanos , Persona de Mediana Edad , Anciano , Rituximab , Lenalidomida , Piperidinas/uso terapéutico , Linfoma de Células B Grandes Difuso/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida
18.
J Am Heart Assoc ; 12(18): e030791, 2023 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-37681524

RESUMEN

Background The renin-angiotensin system plays a crucial role in human physiology, and its main hormone, angiotensin, activates 2 G-protein-coupled receptors, the angiotensin type-1 and type-2 receptors, in almost every organ. However, controversy exists about the location, distribution, and expression levels of these receptors. Concerns have been raised over the low sensitivity, low specificity, and large variability between lots of commercially available antibodies for angiotensin type-1 and type-2 receptors, which makes it difficult to reconciliate results of different studies. Here, we describe the first non-antibody-based sensitive and specific targeted quantitative mass spectrometry assay for angiotensin receptors. Methods and Results Using a technique that allows targeted analysis of multiple peptides across multiple samples in a single mass spectrometry analysis, known as TOMAHAQ (triggered by offset, multiplexed, accurate mass, high resolution, and absolute quantification), we have identified and validated specific human tryptic peptides that permit identification and quantification of angiotensin type-1 and type-2 receptors in biological samples. Several peptide sequences are conserved in rodents, making these mass spectrometry assays amenable to both preclinical and clinical studies. We have used this method to quantify angiotensin type-1 and type-2 receptors in postmortem frontal cortex samples of older adults (n=28) with Alzheimer dementia. We correlated levels of angiotensin receptors to biomarkers classically linked to renin-angiotensin system activation, including oxidative stress, inflammation, amyloid-ß load, and paired helical filament-tau tangle burden. Conclusions These robust high-throughput assays will not only catalyze novel mechanistic studies in the angiotensin research field but may also help to identify patients with an unbalanced angiotensin receptor distribution who would benefit from angiotensin receptor blocker treatment.


Asunto(s)
Angiotensinas , Receptores de Angiotensina , Humanos , Anciano , Sistema Renina-Angiotensina , Antagonistas de Receptores de Angiotensina , Anticuerpos
19.
Cancer ; 118(10): 2571-82, 2012 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-22045610

RESUMEN

Responding to growing concerns regarding the safety, quality, and efficacy of cancer care in the United States, the Institute of Medicine (IOM) of the National Academy of Sciences commissioned a comprehensive review of cancer care delivery in the US health care system in the late 1990s. The National Cancer Policy Board (NCPB), a 20-member board with broad representation, performed this review. In its review, the NCPB focused on the state of cancer care delivery at that time, its shortcomings, and ways to measure and improve the quality of cancer care. The NCPB described an ideal cancer care system in which patients would have equitable access to coordinated, guideline-based care and novel therapies throughout the course of their disease. In 1999, the IOM published the results of this review in its influential report, Ensuring Quality Cancer Care. The report outlined 10 recommendations, which, when implemented, would: 1) improve the quality of cancer care, 2) increase the current understanding of quality cancer care, and 3) reduce or eliminate access barriers to quality cancer care. Despite the fervor generated by this report, there are lingering doubts regarding the safety and quality of cancer care in the United States today. Increased awareness of medical errors and barriers to quality care, coupled with escalating health care costs, has prompted national efforts to reform the health care system. These efforts by health care providers and policymakers should bridge the gap between the ideal state described in Ensuring Quality Cancer Care and the current state of cancer care in the United States.


Asunto(s)
Neoplasias/terapia , Calidad de la Atención de Salud , Benchmarking , Estudios de Seguimiento , Costos de la Atención en Salud , Accesibilidad a los Servicios de Salud , Humanos , Educación del Paciente como Asunto
20.
Comput Biol Med ; 148: 105847, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35932728

RESUMEN

The global pandemic caused by the coronavirus (COVID-19) disease has collapsed the worldwide economy. Elements such as non-obligatory vaccination, new strain variants and lack of discipline to follow social distancing measures suggest the possibility that COVID-19 may continue to exist, exhibiting the behavior of a seasonal disease. As the socio-economic crisis has become unsustainable, all countries are planning strategies to gradually restart their economic and social activities. Initially, several containment measures have been adopted involving social distancing, infection detection tests, and ventilation systems. Despite the implementation of such policies, there exists a lack of evaluation of their performance to reduce the contagion index. This means there are no appropriate indicators to decide which intervention or set of interventions present the most effective result. Under these conditions, the development of models that provide useful information in the design and evaluation of containment measures and re-opening policies is of prime concern. In this paper, a novel approach to model the transmission process of COVID-19 in closed environments is proposed. The proposed model can simulate the effects that result from the complex interaction among individuals when they follow a particular containment measure or re-opening policy. With the proposed model, different hypothetical re-opening policies, that are otherwise impossible to analyze in real conditions, can be tested. Computer experiments demonstrate that the proposed model provides suitable information and realistic predictions, which are appropriate for designing strategies that allow a safe return to economic activities.


Asunto(s)
COVID-19 , Humanos , Pandemias , Políticas , SARS-CoV-2
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