Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 376.418
Filtrar
Mais filtros








Intervalo de ano de publicação
1.
J Colloid Interface Sci ; 606(Pt 2): 1950-1965, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34695762

RESUMO

With the continuous development of cancer nanotechnology, an important trend in the research is to combine the broad application prospects of functional nanomaterials with recent biological discoveries and technological advances. Herein, a cancer cell membrane-camouflaged gold nanocage loading doxorubicin (DOX) and l-buthionine sulfoximine (BSO) (denoted as m@Au-D/B NCs) was constructed as an innovative nanoplatform to confer promising cancer combination therapy by evoking effective ferroptosis and immune responses. Briefly, the loading of BSO and DOX could induce ferroptosis through simultaneous effective glutathione (GSH) consumption and reactive oxygen species (ROS) accumulation. Gold nanocages (AuNCs) with distinct anti-tumor application performance was utilized as ideal nanocarrier for drug loading, evoking photothermal effects and photochemical catalysis to generate more ROS under near-infrared (NIR) irradiation. Moreover, m@Au-D/B NCs-mediated photothermal therapy (PTT) combined with ROS production could repolarize the tumor-associated macrophages (TAMs) from pro-tumor (M2) phenotype to anti-tumor (M1) phenotype, thus improving tumor-suppressive immune environment and then promoting the activation of effector cells and release of pro-inflammatory cytokines, in which the antitumor responses were evoked robustly in a methodical approach. The anti-tumor effects in vivo implied that m@Au-D/B NCs could significantly inhibit tumor growth without severe toxicity. Hence, this homotypic targeting nanosystem could offer an auspicious anticancer access by triggering combination cancer therapy via ferroptosis and tumor-associated macrophage repolarization mechanism.


Assuntos
Ferroptose , Neoplasias , Biomimética , Ouro , Neoplasias/tratamento farmacológico , Terapia Fototérmica , Espécies Reativas de Oxigênio , Macrófagos Associados a Tumor
2.
Talanta ; 237: 122924, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736661

RESUMO

During recent decades, we have witnessed a great improvement in the performance of aptamer-based sensors, specifically when aptamers are combined with new nanomaterials; as a platform for biosensors. The design of hollow carbon-based materials has also received a lot of attention due to its excellent properties in various applications. Herein, we aim at designing hierarchical porous Ni(OH)2 nanosheets on hollow N-doped carbon nanoboxes Ni(OH)2@N-C n-box). In this sense, we obtained the hollow N-C n-box skeletons from the Fe2O3 nanocubes template. The development of label-free electrochemical aptasensor was carried out using the covalently immobilizing NH2-functionalized aptamer on Ni(OH)2@N-C n-box as an efficient substrate. The Ni(OH)2@N-C n-box was characterized using scanning fourier transform infrared spectroscopy (FTIR), X-ray Diffraction (XRD), Brunauer, Emmett and Teller (BET), transmission electron microscopes (TEM) and electron microscopy (FESEM). The electrochemical evaluations clarified the fact that a linear relationship exists between the alpha-fetoprotein (AFP) contents and the charge transfer resistance (Rct) (from 1 fg mL-1 to 100 ng mL-1) with a low detection limit of 0.3 fg mL-1. Moreover, regarding the aptasensor, the superior detection recoveries were experienced in real biological samples, illustrating its great detection performance and practical feasibility. Considering the aptasensor application, these studies showed that Ni(OH)2@N-C n-box possesses different enhanced electrochemical features, making it appropriate as an electrode material for aptasensor application.


Assuntos
Neoplasias , alfa-Fetoproteínas , Biomarcadores Tumorais , Carbono , Técnicas Eletroquímicas , Humanos , Hidróxidos , Níquel , Nitrogênio
3.
Talanta ; 237: 122898, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736714

RESUMO

A nucleolus as a prominent sub-nuclear, membraneless organelle plays a crucial role in ribosome biogenesis, which is in the major metabolic demand in a proliferating cell, especially in aggressive malignancies. We develop a γ-glutamyltranspeptidase (GGT)-activatable indole-quinolinium (QI) based cyanine consisting of a novel tripeptide fragment (Pro-Gly-Glu), namely QI-PG-Glu as a turn-on red fluorescent probe for the rapid detection of GGT-overexpressed A549 cancer cells in vivo. QI-PG-Glu can be triggered by GGT to rapidly release an activated fluorophore, namely HQI, in two steps including the cleavage of the γ-glutamyl group recognized by GGT and the rapid self-driven cyclization of the Pro-Gly linker. HQI exhibits dramatically red fluorescence upon binding to rRNA for imaging of nucleolus in live A549 cells. HQI also intervenes in rRNA biogenesis by declining the RNA Polymerase I transcription, thus resulting in cell apoptosis via a p53 dependent signaling pathway. Our findings may provide an alternative avenue to develop multifunctional cancer cell-specific nucleolus-targeting fluorescent probes with potential anti-cancer effects.


Assuntos
Neoplasias , Quinolinas , Fluorescência , Corantes Fluorescentes , Indóis , Neoplasias/diagnóstico por imagem , Quinolinas/farmacologia , gama-Glutamiltransferase
4.
Anal Chim Acta ; 1189: 339206, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34815029

RESUMO

The extracellular matrix (ECM) plays an essential role in tumor progression and invasion through its continuous remodeling. The growth of most carcinomas is associated with an excessive collagen deposition that provides the proper environment for tumor development and chemoresistance. The α1 chain of a minor human collagen, type XI, is overexpressed in some tumor stroma, but not found in normal stroma. To test the clinical utility of this collagen as a cancer biomarker, specific receptors are needed. Available antibodies do not show enough selectivity or are directed toward the propeptide region that is cleaved when the protein is released to the ECM. Here we show the selection of an aptamer for the specific C-telopeptide region using a 16-mer peptide as the target for the SELEX. The aptamer selected with a Kd of ∼25 nM was able to capture the collagen XI from cell lysates. It was also used for target detection in a mixed antibody-aptamer sandwich assay showing it can be useful for diagnostic purposes in biological fluids.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias , Biomarcadores Tumorais , Colágeno , Matriz Extracelular , Humanos , Neoplasias/diagnóstico
5.
PET Clin ; 17(1): 183-212, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34809866

RESUMO

Artificial intelligence (AI) techniques have significant potential to enable effective, robust, and automated image phenotyping including the identification of subtle patterns. AI-based detection searches the image space to find the regions of interest based on patterns and features. There is a spectrum of tumor histologies from benign to malignant that can be identified by AI-based classification approaches using image features. The extraction of minable information from images gives way to the field of "radiomics" and can be explored via explicit (handcrafted/engineered) and deep radiomics frameworks. Radiomics analysis has the potential to be used as a noninvasive technique for the accurate characterization of tumors to improve diagnosis and treatment monitoring. This work reviews AI-based techniques, with a special focus on oncological PET and PET/CT imaging, for different detection, classification, and prediction/prognosis tasks. We also discuss needed efforts to enable the translation of AI techniques to routine clinical workflows, and potential improvements and complementary techniques such as the use of natural language processing on electronic health records and neuro-symbolic AI techniques.


Assuntos
Inteligência Artificial , Neoplasias , Diagnóstico por Imagem , Humanos , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico
6.
J Colloid Interface Sci ; 606(Pt 2): 1219-1228, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492460

RESUMO

To minimize unwanted reactions with high concentrations of reduced glutathione (GSH) in the tumor microenvironment (TME) during chemodynamic therapy (CDT), a simple and effective strategy was developed to fabricate a TME stimuli-responsive theranostic nanomedicine (Fe-CD) for fluorescence imaging-guided GSH depletion and cancer therapy by combining fluorescent imaging carbon dots (CD) and Fe(III). Introducing Fe(III) into Fe-CD not only quenched the fluorescence of CD while reacting with and consuming intracellular GSH for fluorescence imaging of the depletion of GSH but also provided a source of metal ions to generate more abundant hydroxyl radicals (•OH) with hydrogen peroxide (H2O2) through the Fenton reaction to improve CDT. Fe-CD showed promising •OH generation under H2O2 to effectively degrade methylene blue in vitro and obviously activate the green fluorescence of the reactive oxygen species (ROS) probe in cells. Benefiting from the fluorescence enhancement in response to TME stimulation, Fe-CD greatly enhanced CDT cytotoxicity while monitoring successful GSH depletion by fluorescence imaging. Fe-CD has the potential to act as a theranostic nanomedicine for fluorescence imaging-guided GSH depletion to amplify CDT.


Assuntos
Nanopartículas , Neoplasias , Pontos Quânticos , Carbono , Linhagem Celular Tumoral , Compostos Férricos , Glutationa , Humanos , Peróxido de Hidrogênio , Imagem Óptica , Nanomedicina Teranóstica , Microambiente Tumoral
7.
J Colloid Interface Sci ; 606(Pt 2): 1488-1508, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34500153

RESUMO

The combination of chemotherapy (CT) and chemodynamic therapy (CDT) is an emerging therapeutic strategy for tumors; however, its therapeutic efficacy is usually impaired by the shortage of high-efficiency intracellular catalysts for CDT and the poor tumor selectivity of CT. To address this concern, novel carrier-free nanodrugs (CMC-DD2) self-assembled from the natural melanin complex (CMC) with a superior CDT performance, and dehydroabietic acid hexamer (DD2) displaying a potent antitumor activity were proposed for the synergistic combination of CT and CDT. CMC-DD2 preferred to enter tumor cells and localize in the nucleus after lysosome escape due to its pH-dependent charge-reversal properties. Nanodrugs internalized by the nucleus directly bound the DNA and altered its conformation. Then, the dissociation of CMC-DD2 was efficiently triggered by intracellular hydrogen peroxide (H2O2) with the release of DNA damaging agents, including nitrate anions, hydroxyl radicals (●OH) and DD2. Finally, severe DNA damage induced mitochondrial apoptosis in HepG2 cells. An in vivo assessment further demonstrated the superior tumor selectivity and suppressor capacity and no/low toxicity of the nanodrugs. Overall, novel carrier-free, charge-reversal, nucleus-targeting, biodegradable, and DNA-affinity nanodrugs represent safe and effective platforms for the combination of CT and CDT.


Assuntos
Nanopartículas , Neoplasias , Linhagem Celular Tumoral , DNA , Células Hep G2 , Humanos , Peróxido de Hidrogênio , Radical Hidroxila , Neoplasias/tratamento farmacológico
8.
Dermatol Clin ; 40(1): 73-81, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34799037

RESUMO

The understanding of melanocytes is fundamental to the study of dermatology. These dendritic cells underly the most feared primary cutaneous malignancy, fuel escalating progress in immunotherapy strategies, and invariably underlie entire socioeconomic constructs consciously or unconsciously based on skin tone. Various ethno-genotypes combine with increasing frequency over time, increasing the diversity of skin types that may present with dermatologic diagnoses. Understanding the biology of a variety of skin tones and ethnic practices congruent with distribution of skin tone is invaluable to any physician who wishes to practice efficient and expert care, especially to pediatric patients of this category.


Assuntos
Dermatologia , Neoplasias , Dermatopatias , Criança , Grupos Étnicos , Humanos , Pele , Dermatopatias/terapia , Pigmentação da Pele
9.
Talanta ; 236: 122830, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635220

RESUMO

A sensitive biosensor that can be used for the determination of matrix metalloproteinase 2 (MMP-2) was proposed. The biosensor was developed by using an excellent self-enhanced nanocomposites as an illuminant and a peptide as a recognition element. For the electrostatic attraction between Ru(bpy)32+ and nitrogen-doped graphene quantum dots (NGQDs), the self-enhanced electrochemiluminescence (ECL) nanocomposites of NGQDs-Ru(bpy)32+-doped silica nanoparticles (NGQDs-Ru@SiO2) were synthesized through a simple sol-gel process. Then, a specific peptide (labeled sulfhydryl) was combined with the self-enhanced ECL nanocomposites (carboxyl in NGQDs) via acylation reaction to obtain the peptide-NGQDs-Ru@SiO2 nanoprobe, which was fabricated onto the gold electrode surface via Au-S bond. The peptide of the ECL nanoprobe was exposed to cleavage in the presence of MMP-2, which caused the signal substance to move farther away from the electrode, leading to a decrease of the ECL signal. The proposed NGQDs-Ru@SiO2-labeled peptide ECL biosensor displayed a lower detection limit of 6.5 pg mL-1 than those of reported ECL methods. The proposed biosensor provided an outlook for future applications in other disease-associated biomarkers.


Assuntos
Técnicas Biossensoriais , Grafite , Neoplasias , Pontos Quânticos , Biomarcadores Tumorais , Técnicas Eletroquímicas , Humanos , Medições Luminescentes , Metaloproteinase 2 da Matriz , Nitrogênio , Dióxido de Silício
10.
Biosens Bioelectron ; 195: 113626, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34543916

RESUMO

MXenes are a new class of conductive two-dimensional material which have received growing attention in biosensing for their significant surface area and unique surface chemistry. Here, gold electrodes were modified with MXene nanosheets of about 2 nm thickness and 1.5 µm lateral size for the electrochemical detection of tumor cells. An HB5 aptamer with high selectivity for HER-2 positive cells was immobilized on the MXene layers via electrostatic interactions. To minimize electrode biofouling with blood matrix, magnetic separation of HER-2 positive circulating tumor cells was carried out using CoFe2O4@Ag magnetic nanohybrids bonded to the HB5. The formation of sandwich-like structures between the magnetically captured cells and the functionalized MXene electrodes effectively shields the electron transfer of a redox probe, enabling quantitative cell detection using the change in current. This label-free MXene-based cytosensor platform yielded a wide linear range of 102-106 cells/mL, low detection limit of 47 cells/mL, and good sensitivity and selectivity in the detection of HER2-posetive cells in blood samples. The presented aptacytosensor demonstrates the great potential of using CoFe2O4@Ag magnetic nanohybrids and MXenes to monitor cancer progression via circulating tumor cells in blood at low cost.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Neoplasias , Técnicas Eletroquímicas , Eletrodos , Ouro , Limite de Detecção , Fenômenos Magnéticos
11.
Biosens Bioelectron ; 195: 113653, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34563889

RESUMO

Studies over the last decade have shown that matrix metalloproteinases (MMPs) play a key role in the growth and metastasis of cancer. This zinc-dependent family of endopeptidases is crucial for the degradation of extracellular matrix (ECM), as well as serves as important ECM transducers which have been recognized as early biomarkers for both cancer diagnosis and treatment. In this study, we designed a new type of voltammetric biosensor, composed of a glycine-methionine dipeptide conjugated covalently to ferrocene (Gly-Met-Fc), for fast and ultrasensitive detection of the active form of MMP-9 in plasma samples. The detection was based on specific enzymatic cleavage of the Gly-Met peptide bond, which was monitored by voltammetry and gravimetry measurements. The ferrocene units act as voltammetric visualizers for the detection process. The cysteamine layer directly anchored to the gold surface ensured that the packing density of Gly-Met-Fc in the receptor layer was appropriate for the sensitive detection of MMP-9 in its active form. The developed biosensor was characterized by the widest analytical range (2.0·10-6 - 5.0 µg⋅mL-1) and low detection limit (0.04 pg⋅mL-1). Another valuable feature of the proposed biosensor is that it can be applied directly to the plasma samples without any additional preparation step and thus speeds up the analysis.


Assuntos
Técnicas Biossensoriais , Neoplasias , Biomarcadores Tumorais , Dipeptídeos , Humanos , Metaloproteinase 9 da Matriz , Metalocenos , Prognóstico
12.
Biosens Bioelectron ; 195: 113644, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34571478

RESUMO

Cancer epigenomic-environment is a core center of a tumor's genetic and epigenetic configuration. Surveying epigenomic-environment of cancer stem-like cells (CSC) is vital for developing novel diagnostic methods and improving current therapies since CSCs are among the most challenging clinical hurdles. To date, there exists no technique which can successfully monitor the epigenomics of CSC. Here, we have developed unique sub-10 nm Self-functional Gold Nanoprobes (GNP) as a CSC epigenomic monitoring platform that can easily maneuver into the nucleus while not producing any conformal changes to the genomic DNA. The GNP was synthesized using physical synthesis method of pulsed laser multiphoton ionization, which enabled the shrinking of GNP to 2.69 nm which helped us achieve two critical parameters for epigenomics monitoring: efficient nuclear uptake (98%) without complex functionalization and no conformational nuclear changes. The GNP efficiently generated SERS for structural, functional, molecular epigenetics, and nuclear proteomics in preclinical models of breast and lung CSCs. To the best of knowledge, this study is first to utilize the intranuclear epigenomic signal to distinguish between CSC from different tissues with >99% accuracy and specificity. Our findings are anticipated to help advance real-time epigenomics surveillance technologies such as nucleus-targeted drug surveillance and epigenomic prognosis and diagnostics.


Assuntos
Técnicas Biossensoriais , Neoplasias , Epigenômica , Ouro , Humanos , Células-Tronco Neoplásicas
13.
Biosens Bioelectron ; 195: 113654, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34592499

RESUMO

We have developed a novel cancer theragnostic nanoassembly with high biocompatibility, stability and low toxicity which are activated rapidly by tumor microenvironment to realize selective fluorescence imaging, chemotherapy as well as chemoenzymatic therapy. The nanoprobes are synthesized by hybridization of fluorophore labeled hairpin DNAs containing a 5-aza-dC at hemimethylated CpG sites and pH-sensitive DNA sequence covalently conjugated with PEGylated GO. The aptamer, which is also covalently conjugated on PEGylated GO, enables to target the tumor site and the weak acid environment of tumor triggers the release of drug loaded by nanoprobes including functionalized DNA and DOXs, effectively activating fluorescence signals and selectively killing the tumor cells. The results revealed that the nanoprobe enables sensitive detection of pH changes within subcellular environment, selectively imaging and great synergy of multicombination therapeutic including chemotherapy and chemoenzymatic therapy, implying that developed pH activatable probe has considerable potential for diagnosis and efficient therapy of cancer.


Assuntos
Técnicas Biossensoriais , Neoplasias , DNA/genética , Humanos , Concentração de Íons de Hidrogênio , Neoplasias/tratamento farmacológico , Neoplasias/genética , Hibridização de Ácido Nucleico , Microambiente Tumoral
14.
Biosens Bioelectron ; 195: 113671, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34624798

RESUMO

The extracellular matrix (ECM) of tumor mediates malignant transformation and distant metastasis with extracellular proteinases, especially the matrix metalloproteinases (MMPs). However, there is no assay method to trace the dynamic content of MMPs in ECM. In this work, we have proposed a strategy by assembling peptide scaffold on ionic nanochannels to monitor the target proteinases. The short peptide unit is designed to induce self-assembly with good stability, biocompatibility and programmability, while ion nanochannels can provide electrochemical response upon the MMP activities. Taking MMP-2 as an example, the peptide unit includes two regions, one for self-assembly and one for bio-recognition, so the assembly region (KLVFF) can self-assemble to nanofiber networks. In the meantime, since the reactive region (PLGVR) has MMP-2 recognition site, the peptide assembly on nanochannel can thus be used for the detection of active MMP-2 in tumor microenvironment, with a wide linear detection range (10 fg/mL-10 ng/mL) and 6.6 fg/mL limit of detection. Moreover, the availability of the established ECM mimic is able to distinguish active MMP-2 from latent proMMP-2 in tumor samples. By designing different peptide units for self-assembly on the ionic nanochannel, the assay platform can be promisingly used for other proteinases in ECM, so this work may provide a useful approach to trace the dynamic content of the MMPs in tumor microenvironment (TEM).


Assuntos
Técnicas Biossensoriais , Neoplasias , Matriz Extracelular , Humanos , Metaloproteinase 2 da Matriz , Metaloproteinases da Matriz , Microambiente Tumoral
15.
J Colloid Interface Sci ; 605: 752-765, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34365311

RESUMO

One major challenge of photothermal therapy (PTT) is achieving thermal ablation of the tumor without damaging the normal cells and tissues. Here, we designed a self-regulating photothermal conversion system for selective thermotherapy based on self-assembling gold nanoparticles (S-AuNPs) and investigated the selectivity effect using a novel home-made in vitro selective photothermal transformation model and an in vivo skin damaging assessment model. In the in vitro selective photothermal transformation model, laser irradiation selectively increased the temperature of the internal microenvironment (pH 5.5) and resulted in an obvious temperature difference (ΔT ≥ 5 °C) with that of the external environment (pH 7.4). More importantly, in the in vivo skin damaging assessment model, S-AuNPs achieved good tumor inhibition without damaging the normal skin tissue compared with the conventional photothermal material. This work provides not only a novel validation protocol for tumor thermotherapy to achieve the biosafety of specifically killing tumor cells and normal tissue but also an evaluation methodology for other precise therapy for cancers.


Assuntos
Hipertermia Induzida , Nanopartículas Metálicas , Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Ouro , Humanos , Neoplasias/terapia , Fototerapia , Microambiente Tumoral
16.
J Colloid Interface Sci ; 605: 851-862, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34371428

RESUMO

Photodynamic therapy (PDT) of tumor has achieved good results, but the treatment efficiency is not high due to the lack of effective photosensitizers and tumor hypoxia. In this study, iridium dioxide nanoparticles (IrO2 NPs) with excellent photothermal/photodynamic effects and catalase like activity were synthesized by a simple method. The combination of glucose oxidase (GOx) and IrO2 NPs is formed by hyaluronic acid (HA), which have the activities of glucose oxidase and catalase, can target tumor sites and form in situ amplifiers in tumor microenvironment (IrO2-GOx@HA NPs). Firstly, GOx convert the high levels of glucose in the tumor to hydrogen peroxide (H2O2), and then IrO2 NPs convert H2O2 to oxygen (O2), which can enhance the type II of PDT. IrO2 NPs also can be used as a thermosensitive agent for photothermal therapy (PTT). In cancer cells, IrO2-GOx@HA NPs-mediated amplifier enhances the effect of type II of PDT, aggravating the apoptosis of breast cancer (4T1) cells and cooperating with its own PTT to further improve the overall treatment effect. Under simulated hypoxic conditions of tumor tissue, it was found that IrO2-GOx@HA NPs treatment can effectively relieve hypoxia inside tumor tissue. In addition, the results in vivo further proved that, IrO2-GOx@HA NPs can enhance the role of II PDT and cooperate with PTT to treat breast cancer effectively. The results highlight the prospect of IrO2-GOx@HA NPs in controlling and regulating tumor hypoxia to overcome the limitations of current cancer therapy.


Assuntos
Neoplasias da Mama , Nanopartículas , Neoplasias , Fotoquimioterapia , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Humanos , Peróxido de Hidrogênio , Irídio , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Terapia Fototérmica , Microambiente Tumoral
17.
Chemosphere ; 286(Pt 2): 131811, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34365169

RESUMO

As humans are always exposed to multiple pesticides, it is necessary to conduct risk assessments for pesticide mixtures. Due to data limitations, in this study, we introduced a disease-specific screening-level modeling framework to simulate the cumulative cancer risk (CR) of carcinogenic pesticides, which was developed based on the lognormal dose-response (LDR) curve of chemicals with disease-specific modes of action (MOAs). The simulated results of a case study indicate that the cumulative CR can be at least two orders of magnitude higher than the simulated CRs of individual pesticides. The comparison between the LDR model and the linear extrapolation (or cancer slope factor, CSF) model indicates that the CSF model can greatly overestimate population cancer risks. In addition, we applied our model to evaluate current regulatory standards of carcinogenic pesticide mixtures, and the results indicate that current standards for the selected jurisdictions can control the cumulative cancer risks within the acceptable level. However, the CSF model suggests that all selected jurisdictions cannot protect population health against the carcinogenic pesticide mixture, which is due to the nature of the low-dose linear extrapolation that triggers an initial slope when the effect dose is close to zero. Thus, we concluded that although the MOAs of pesticides in human bodies must be evaluated in future studies, our disease-specific model can be a useful and practical tool for cancer risk assessment and regulatory management of pesticide mixtures.


Assuntos
Neoplasias , Praguicidas , Carcinógenos/toxicidade , Detecção Precoce de Câncer , Humanos , Neoplasias/induzido quimicamente , Praguicidas/toxicidade , Medição de Risco
18.
Sci Total Environ ; 803: 149923, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34487898

RESUMO

While it is often assumed that oncogenic processes in metazoans can influence species interactions, empirical evidence is lacking. Here, we use the cnidarian Hydra oligactis to experimentally explore the consequences of tumor associated phenotypic alterations for its predation ability, relationship with commensal ciliates and vulnerability to predators. Unexpectedly, hydra's predation ability was higher in tumorous polyps compared to non-tumorous ones. Commensal ciliates colonized preferentially tumorous hydras than non-tumorous ones, and had a higher replication rate on the former. Finally, in a choice experiment, tumorous hydras were preferentially eaten by a fish predator. This study, for the first time, provides evidence that neoplastic growth has the potential, through effect(s) on host phenotype, to alter biotic interactions within ecosystems and should thus be taken into account by ecologists.


Assuntos
Cnidários , Hydra , Neoplasias , Animais , Ecossistema , Água Doce
19.
J Colloid Interface Sci ; 607(Pt 1): 34-44, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34492351

RESUMO

Among the strategies to fight cancer, multi-therapeutic approaches are considered as a wise choice to put in place multiple weapons to suppress tumors. In this work, to combine chemotherapeutic effects to magnetic hyperthermia when using biocompatible scaffolds, we have established an electrospinning method to produce nanofibers of polycaprolactone loaded with magnetic nanoparticles as heat mediators to be selectively activated under alternating magnetic field and doxorubicin as a chemotherapeutic drug. Production of the fibers was investigated with iron oxide nanoparticles of peculiar cubic shape (at 15 and 23 nm in cube edges) as they provide benchmark heat performance under clinical magnetic hyperthermia conditions. With 23 nm nanocubes when included into the fibers, an arrangement in chains was obtained. This linear configuration of magnetic nanoparticles resemble that of the magnetosomes, produced by magnetotactic bacteria, and our magnetic fibers exhibited remarkable heating effects as the magnetosomes. Magnetic fiber scaffolds showed excellent biocompatibility on fibroblast cells when missing the chemotherapeutic agent and when not exposed to magnetic hyperthermia as shown by viability assays. On the contrary, the fibers containing both magnetic nanocubes and doxorubicin showed significant cytotoxic effects on cervical cancer cells following the exposure to magnetic hyperthermia. Notably, these tests were conducted at magnetic hyperthermia field conditions of clinical use. As here shown, on the doxorubicin sensitive cervical cancer cells, the combination of heat damage by magnetic hyperthermia with enhanced diffusion of doxorubicin at therapeutic temperature are responsible for a more effective oncotherapy.


Assuntos
Hipertermia Induzida , Nanopartículas de Magnetita , Neoplasias , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Compostos Férricos , Campos Magnéticos , Poliésteres
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 266: 120458, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34619508

RESUMO

Near-infrared (NIR) photothermal therapy is an effective partner to the chemotherapy of tumors with the merits of high therapeutic ability and slight side effect on normal tissues. Herein, we synthesized gold nanorods and assembled them with L-cysteine reduced graphene oxide (AuNR@Lcyst-rGO) for efficient photothermal therapy. The high therapeutic efficacy of AuNR@Lcyst-rGO can be due to the high photothermal effect of gold nanorods and reduced graphene oxide, and the synergistic effect of them. The nontoxicity of L-cysteine also guarantees the comfortable biocompatibility of reduced graphene oxide, which is essential for the photothermal absorber used in human tissue. The results demonstrate that assembly of gold nanorods with reduced graphene oxide (AuNR@Lcyst-rGO) is a promising photothermal agent with high efficient NIR-triggered photothermal therapy efficiency, excellent stability, superior biocompatibility.


Assuntos
Grafite , Nanotubos , Neoplasias , Linhagem Celular Tumoral , Cisteína , Ouro , Humanos , Neoplasias/terapia , Fototerapia , Terapia Fototérmica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA