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1.
Int Immunopharmacol ; 133: 112047, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38631221

RESUMO

BACKGROUND: Glioma is a primary tumor originating from the central nervous system, and despite ongoing efforts to improve treatment, its overall survival rate remains low. There are a limited number of reports regarding the clinical grading, prognostic impact, and utility of chemokines. Therefore, conducting a meta-analysis is necessary to obtain convincing and conclusive results. METHODS: A comprehensive literature search was conducted using various databases, including PubMed, Web of Science, The Cochrane Library, Embase, Ovid Medline, CNKI, Wanfang Database, VIP, and CBM. The search encompassed articles published from the inception of the databases until March 2024. The estimated odds ratio (ORs), standard mean difference (SMDs), and hazard ratio (HR) with their corresponding 95% confidence intervals (95% CI) were calculated to assess the predictive value of chemokine and receptor levels in glioma risk. Additionally, heterogeneity tests and bias tests were performed to evaluate the reliability of the findings. RESULTS: This meta-analysis included a total of 36 studies, involving 2,480 patients diagnosed with glioma. The results revealed a significant association between the expression levels of CXCR4 (n = 8; OR = 22.28; 95 % CI = 11.47-43.30; p = 0.000), CXCL12 (n = 4; OR = 10.69; 95 % CI = 7.03-16.24; p = 0.000), CCL2 (n = 6; SMD = -0.83; 95 % CI = -0.98--0.67; p = 0.000), CXCL8 (n = 3; SMD = 0.75; 95 % CI = 0.47-1.04; p = 0.000), CXCR7 (n = 3; OR = 20.66; 95 % CI = 10.20-41.82; p = 0.000), CXCL10 (n = 2; SMD = 3.27; 95 % CI = 2.91-3.62; p = 0.000) and the risk of glioma. Additionally, a significant correlation was observed between CXCR4 (n = 8; OR = 4.39; 95 % CI = 3.04-6.32; p = 0.000), (n = 6; SMD = 1.37; 95 % CI = 1.09-1.65; p = 0.000), CXCL12 (n = 6; OR = 6.30; 95 % CI = 3.87-10.25; p = 0.000), (n = 5; ES = 2.25; 95 % CI = 1.15-3.34; p = 0.041), CCL2 (n = 3; OR = 9.65; 95 % CI = 4.55-20.45; p = 0.000), (n = 4; SMD = -1.47; 95 % CI = -1.68--1.26; p = 0.000), and CCL18 (n = 3; SMD = 1.62; 95 % CI = 1.30-1.93; p = 0.000) expression levels and high-grade glioma (grades 3-4). Furthermore, CXCR4 (HR = 2.38, 95 % CI = 1.66-3.40; p = 0.000) exhibited a strong correlation with poor overall survival (OS) rates in glioma patients. CONCLUSION: The findings of this study showed a robust association between elevated levels of CXCR4, CXCL12, CCL2, CXCL8, CXCL10 and CXCR7 with a higher risk of glioma. Furthermore, the WHO grading system was validated by the strong correlation shown between higher expression of CXCR4, CXCL12, CCL2, and CCL18 and WHO high-grade gliomas (grades 3-4). Furthermore, the results of the meta-analysis suggested that CXCR4 might be a helpful biomarker for predicting the worse prognosis of glioma patients.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Glioma/mortalidade , Glioma/imunologia , Glioma/metabolismo , Prognóstico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/imunologia , Biomarcadores Tumorais/metabolismo , Quimiocinas/metabolismo , Receptores de Quimiocinas/metabolismo , Receptores CXCR4/metabolismo
2.
Chem Commun (Camb) ; 60(29): 3978-3981, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38502001

RESUMO

We designed a novel ratiometric fluorescence immunoassay based on bioorthogonal nanozymes for carcinoembryonic antigen detection. The analytical performance of our designed immunoassay showed a wide linear range, a low detection limit, good reproducibility, selectivity and stability. Thus, bioorthogonal nanozymes hold great potential applications in clinical diagnoses.


Assuntos
Antígeno Carcinoembrionário , Reprodutibilidade dos Testes , Imunoensaio
3.
Small ; : e2307961, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38126911

RESUMO

Activating the stimulator of the interferon gene (STING) is a promising immunotherapeutic strategy for converting "cold" tumor microenvironment into "hot" one to achieve better immunotherapy for malignant tumors. Herein, a manganese-based nanotransformer is presented, consisting of manganese carbonyl and cyanine dye, for MRI/NIR-II dual-modality imaging-guided multifunctional carbon monoxide (CO) gas treatment and photothermal therapy, along with triggering cGAS-STING immune pathway against triple-negative breast cancer. This nanosystem is able to transfer its amorphous morphology into a crystallographic-like formation in response to the tumor microenvironment, achieved by breaking metal-carbon bonds and forming coordination bonds, which enhances the sensitivity of magnetic resonance imaging. Moreover, the generated CO and photothermal effect under irradiation of this nanotransformer induce immunogenic death of tumor cells and release damage-associated molecular patterns. Simultaneously, the Mn acts as an immunoactivator, potentially stimulating the cGAS-STING pathway to augment adaptive immunity, resulting in promoting the secretion of type I interferon, the proliferation of cytotoxic T lymphocytes and M2-macrophages repolarization. This nanosystem-based gas-photothermal treatment and immunoactivating therapy synergistic effect exhibit excellent antitumor efficacy both in vitro and in vivo, reducing the risk of triple-negative breast cancer recurrence and metastasis; thus, this strategy presents great potential as multifunctional immunotherapeutic agents for cancer treatment.

4.
Front Oncol ; 13: 1124069, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37197418

RESUMO

Objective: To investigate the predictive value of contrast-enhanced computed tomography (CECT) imaging features and clinical factors in identifying the macrotrabecular-massive (MTM) subtype of hepatocellular carcinoma (HCC) preoperatively. Methods: This retrospective study included 101 consecutive patients with pathology-proven HCC (35 MTM subtype vs. 66 non-MTM subtype) who underwent liver surgery and preoperative CECT scans from January 2017 to November 2021. The imaging features were evaluated by two board-certified abdominal radiologists independently. The clinical characteristics and imaging findings were compared between the MTM and non-MTM subtypes. Univariate and multivariate logistic regression analyses were performed to investigate the association of clinical-radiological variables and MTM-HCCs and develop a predictive model. Subgroup analysis was also performed in BCLC 0-A stage patients. Receiver operating characteristic (ROC) curves analysis was used to determine the optimal cutoff values and the area under the curve (AUC) was employed to evaluate predictive performance. Results: Intratumor hypoenhancement (odds ratio [OR] = 2.724; 95% confidence interval [CI]: 1.033, 7.467; p = .045), tumors without enhancing capsules (OR = 3.274; 95% CI: 1.209, 9.755; p = .03), high serum alpha-fetoprotein (AFP) (≥ 228 ng/mL, OR = 4.101; 95% CI: 1.523, 11.722; p = .006) and high hemoglobin (≥ 130.5 g/L; OR = 3.943; 95% CI: 1.466, 11.710; p = .009) were independent predictors for MTM-HCCs. The clinical-radiologic (CR) model showed the best predictive performance, achieving an AUC of 0.793, sensitivity of 62.9% and specificity of 81.8%. The CR model also effectively identify MTM-HCCs in early-stage (BCLC 0-A stage) patients. Conclusion: Combining CECT imaging features and clinical characteristics is an effective method for preoperatively identifying MTM-HCCs, even in early-stage patients. The CR model has high predictive performance and could potentially help guide decision-making regarding aggressive therapies in MTM-HCC patients.

5.
Acta Biomater ; 166: 567-580, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37207741

RESUMO

Tumor-associated enzyme activated prodrug is a potential strategy to overcome the limitations of chemotherapeutic agents. However, the efficiency of enzymatic prodrug activation is limited by the inability to reach adequate enzyme levels in vivo. Herein, we report an intelligent nanoplatform with cyclic amplification of intracellular reactive oxygen species (ROS) that significantly up-regulates the expression of tumor-associated enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1), to efficiently activate the prodrug of doxorubicin (DOX) for enhanced chemo-immunotherapy. The nanoplatform termed as CF@NDOX was fabricated by self-assembly of the amphiphilic cinnamaldehyde (CA) containing poly(thioacetal) conjugated with ferrocene (Fc) and poly(ethylene glycol) (PEG) (TK-CA-Fc-PEG), which further encapsulated the NQO1 responsive prodrug of DOX (NDOX). After CF@NDOX accumulates in tumors, the TK-CA-Fc-PEG with ROS responsive thioacetal group responds to endogenous ROS in tumor to release CA, Fc or NDOX. CA induces mitochondria dysfunction and elevates the intracellular hydrogen peroxide (H2O2) levels, which react with Fc to generate highly oxidative hydroxyl radical (•OH) through Fenton reaction. The •OH not only promotes ROS cyclic amplification but also increase the expression of NQO1 through Keap1-Nrf2 pathway regulation, which further boost the prodrug activation of NDOX for enhanced chemo-immunotherapy. Overall, our well-designed intelligent nanoplatform provides a tactic to enhance the antitumor efficacy of tumor-associated enzyme activated prodrug. STATEMENT OF SIGNIFICANCE: In this work, a smart nanoplatform CF@NDOX with intracellular ROS cyclic amplification for continuous upregulation of NQO1 enzyme expression was innovatively designed. It could utilize Fenton reaction of Fc to increase the level of NQO1 enzyme and CA to increase the level of intracellular H2O2, thereby facilitating the continuous Fenton reaction. This design allowed for a sustained elevation of the NQO1 enzyme, and a more complete activation of the NQO1 enzyme in response to the prodrug NDOX. This smart nanoplatform can achieve a desirable anti-tumor effect with the combined therapy of chemotherapy and ICD effects.


Assuntos
Nanopartículas , Neoplasias , Pró-Fármacos , Humanos , Pró-Fármacos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Peróxido de Hidrogênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Doxorrubicina/farmacologia , Linhagem Celular Tumoral
6.
Acta Biomater ; 164: 511-521, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37004782

RESUMO

Photodynamic therapy (PDT), as a non-invasive and spatiotemporally controllable modality, exhibits great potential in cancer treatment. However, the efficiency of reactive oxygen species (ROS) production was restricted to the hydrophobic characteristics and aggregation-caused quenching (ACQ) of photosensitizers. Herein, we designed a ROS self-activatable nano system (denoted as PTKPa) based on poly(thioketal) conjugated with photosensitizers (PSs) pheophorbide A (Ppa) on the polymer side chains for suppressing ACQ and enhancing PDT. The process of self-activation is that ROS, which is derived from laser irradiated PTKPa, as an activating agent accelerates poly(thioketal) cleavage with the release of Ppa from PTKPa. This in turn generates abundant ROS, accelerates degradation of the remaining PTKPa and amplifies the efficacy of PDT with more tremendous ROS generated. Moreover, these abundant ROS can amplify PDT-induced oxidative stress, cause irreversible damage to tumor cells and achieve immunogenic cell death (ICD), thereby boosting the efficacy of photodynamic-immunotherapy. These findings provide new insights into ROS self-activatable strategy for enhancing cancer photodynamic- immunotherapy. STATEMENT OF SIGNIFICANCE: This work described an approach to utilize ROS-responsive self-activatable poly(thioketal) conjugated with pheophorbide A (Ppa) for suppressing aggregation-caused quenching (ACQ) and enhancing photodynamic-immunotherapy. The ROS, generated from the conjugated Ppa upon 660nm laser irradiation, as a triggering agent which initiates the release of Ppa with poly(thioketal) degradation. That in turn generates abundant ROS and facilitates degradation of the remaining PTKPa, resulting in oxidative stress to tumor cells and achieving immunogenic cell death (ICD). This work provides a promising solution to improve tumor photodynamic therapeutic effects.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias/tratamento farmacológico , Imunoterapia , Linhagem Celular Tumoral , Nanopartículas/química
7.
Metab Brain Dis ; 37(8): 2979-2993, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36301458

RESUMO

Temozolomide (TMZ) resistance limits its use in glioblastoma (GBM). Exosomes can carry circular RNAs (circRNAs) to regulate chemoresistance. To date, the role of exosomal hsa_circ_0043949 (circ_0043949) in GBM resistance to TMZ is unclear. Relative expression of circ_0043949 in clinical samples, GBM cell lines, and exosomes was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The half-maximal inhibitory concentration (IC50) of TMZ, cell proliferation, apoptosis, invasion, and migration were analyzed via MTT, EdU, flow cytometry, transwell, and wound-healing assays. Relative protein levels were evaluated by western blotting. Target relationship was predicted by bioinformatics analysis and validated by dual-luciferase reporter and RNA pull-down assays. Exosomes were isolated by ultracentrifugation and verified by transmission electron microscopy, nanoparticle tracking analysis (NTA), and western blotting. The effect of exosomal circ_0043949 on TMZ resistance was validated by xenograft assay. Higher expression of circ_0043949 was gained in TMZ-resistant GBM samples and cells. Inhibition of circ_0043949 reduced TMZ resistance via decreasing IC50 of TMZ, repressing proliferation, invasion, migration, and inducing apoptosis in TMZ-resistant GBM cells. Circ_0043949 mediated integrinalpha1 (ITGA1) expression via function as a miR-876-3p sponge. Circ_0043949 was also upregulated in TMZ-resistant GBM cells-derived exosomes, and exosomal circ_0043949 increased the resistance of TMZ-resistant GBM cells to TMZ in xenograft models. TMZ-resistant GBM cells-derived exosomal circ_0043949 promoted TMZ resistance via upregulating ITGA1 expression via sequestering miR-876-3p, offering a potential target for the treatment of TMZ resistance in GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Integrina alfa1 , MicroRNAs , RNA Circular , Temozolomida , Humanos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , MicroRNAs/genética , Oncogenes , Temozolomida/farmacologia , Temozolomida/uso terapêutico , RNA Circular/genética , Integrina alfa1/genética
8.
Sci Rep ; 12(1): 13109, 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35908077

RESUMO

The advancing front method (AFM) is one of the widely used unstructured grid generation techniques. However, the efficiency is relatively low because only one cell is generated in the advancing procedure. In this work, a novel automatic isotropic triangle generation technique is developed by introducing an artificial neural network (ANN) based advancing double-front method (ADFM) to improve the mesh generation efficiency. First, a variety of different patterns are extracted from the AFM mesh generation method and extended to the ADFM method. The mesh generation process in each pattern is discussed in detail. Second, an initial isotropic triangular mesh is generated by the traditional mesh generation method, and then an approach for automatic extraction of the training dataset is proposed. The preprocessed dataset is input into the ANN to train the network, then some typical patterns are obtained through learning. Third, after inputting the initial discrete boundary as initial fronts, the grid is generated from the shortest front and adjacent front. The coordinates of the points contained in the dual fronts and the adjacent points are sent into the neural network as the grid generation environment to obtain the most possible mesh generation pattern, the corresponding methods are used to update the advancing front until the whole computational domain is covered by initial grids, and finally, some smoothing techniques are carried out to improve the quality initial grids. Several typical cases are tested to validate the effectiveness. The experimental results show that the ANN can accurately identify mesh generation patterns, and the mesh generation efficiency is 50% higher than that of the traditional single-front AFM.

9.
Comput Intell Neurosci ; 2022: 1026494, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35707202

RESUMO

In this study, magnetic resonance imaging (MRI) was used to evaluate the relapse features of patients with Rolandic meningioma after the microsurgery. 53 patients with Rolandic meningioma were selected as the research objects, and they were divided into the relapse group (n = 16) and nonrelapse group (n = 37) according to whether patients had a relapse during the follow-up period. Differences in quality of life, 1H-MRS index, vascular density, and cell proliferation between the two groups were assessed as well as imaging differences between the two groups were analyzed using MRI. The results showed that the patients' quality-of-life scores in the two groups increased notably after the surgical treatment (P < 0.05). Compared with the nonrelapse group, the proportion of irregular boundary and uneven enhancement of focal tissue in the relapse group was signally increased (P < 0.05). Compared with the nonrelapse group, cell proliferation index, vascular density and imaging index, mean tumor diameter, mean transit time (MTT), time to peak (TTP), fractional anisotropy (FA), choline (Cho)/N-acetylaspartic acid (NAA), Cho/creatine (Cr), lactic acid (Lac)/Cr, and the maximum value of relative cerebral blood volume (rCBVmax) in the relapse group were obviously increased (P < 0.05). However, the apparent dispersion coefficient, NAA/Cr, and Lac/NAA values decreased greatly (P < 0.05). To sum up, the microsurgical treatment helped improve the quality of life of patients with Rolandic meningioma, and MR imaging could be used to determine the relapse of Rolandic meningioma after microsurgical treatment.


Assuntos
Neoplasias Meníngeas , Meningioma , Ácido Aspártico , Colina , Creatina , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética/métodos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Recidiva Local de Neoplasia/diagnóstico por imagem , Qualidade de Vida
10.
Biomater Adv ; 133: 112616, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35525734

RESUMO

Photodynamic therapy (PDT) is a promising non-invasive and selective cancer treatment. However, its efficacy is curtailed by tumor hypoxia and high levels of glutathione (GSH) in the tumor and addressing both limitations simultaneously remain challenging. Here, an all-in-one nanoplatform was designed using a GSH-responsive nitric oxide (NO) nano-prodrug that synchronously depletes GSH and relieves hypoxia in tumors, enhancing PDT efficacy. The nano-prodrug PEG-PAMAM-PA/SNO was prepared by integrating the GSH-sensitive NO and pheophorbide A (PA) prodrugs N-acetyl-d-penicillamine thiolactone and PAMAM-PA into polyethylene glycol (PEG), and the NPPA/NO and NPPA were then obtained through nanoprecipitation method. This nanoplatform depletes the intracellular antioxidant, GSH, by integrating GSH-responsive NO prodrug and generating NO that relaxes blood vessels, thereby relieving tumor hypoxia and defeating antioxidant defense system in tumor, while PEGylated PAMAM dendrimers have abundant surface functional groups and can greatly prolong their circulation lifetime in the bloodstream. These effects make this GSH-activatable NO nano-prodrug platform an appealing strategy for enhancing PDT's antitumor effects.


Assuntos
Neoplasias , Fotoquimioterapia , Pró-Fármacos , Antioxidantes , Glutationa , Humanos , Hipóxia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Óxido Nítrico , Polietilenoglicóis , Pró-Fármacos/farmacologia
11.
Pharmaceutics ; 14(1)2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-35056948

RESUMO

ß-cyclodextrin(ßCD)-based star polymers have attracted much interest because of their unique structures and potential biomedical and biological applications. Herein, a well-defined folic acid (FA)-conjugated and disulfide bond-linked star polymer ((FA-Dex-SS)-ßCD-(PCL)14) was synthesized via a couple reaction between ßCD-based 14 arms poly(ε-caprolactone) (ßCD-(PCL)14) and disulfide-containing α-alkyne dextran (alkyne-SS-Dex), and acted as theranostic nanoparticles for tumor-targeted MRI and chemotherapy. Theranostic nanoparticles were obtained by loading doxorubicin (DOX), and superparamagnetic iron oxide (SPIO) particles were loaded into the star polymer nanoparticles to obtain ((FA-Dex-SS)-ßCD-(PCL)14@DOX-SPIO) theranostic nanoparticles. In vitro drug release studies showed that approximately 100% of the DOX was released from disulfide bond-linked theranostic nanoparticles within 24 h under a reducing environment in the presence of 10.0 mM GSH. DOX and SPIO could be delivered into HepG2 cells efficiently, owing to the folate receptor-mediated endocytosis process of the nanoparticles and glutathione (GSH), which triggered disulfide-bonds cleaving. Moreover, (FA-Dex-SS)-ßCD-(PCL)14@DOX-SPIO showed strong MRI contrast enhancement properties. In conclusion, folic acid-decorated reduction-sensitive star polymeric nanoparticles are a potential theranostic nanoparticle candidate for tumor-targeted MRI and chemotherapy.

12.
Int J Nanomedicine ; 15: 3023-3038, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431499

RESUMO

INTRODUCTION: Advanced tumor-targeted theranostic nanoparticles play a key role in tumor diagnosis and treatment research. In this study, we developed a multifunctional theranostic platform based on an amphiphilic hyaluronan/poly-(N-ε-carbobenzyloxy-L-lysine) derivative (HA-g-PZLL), superparamagnetic iron oxide (SPIO) and aggregation-induced emission (AIE) nanoparticles for tumor-targeted magnetic resonance (MR) and fluorescence (FL) dual-modal image-guided photodynamic therapy (PDT). MATERIALS AND METHODS: The amphiphilic hyaluronan acid (HA) derivative HA-g-PZLL was synthesized by grafting hydrophobic poly-(N-ε-carbobenzyloxy-L-lysine) (PZLL) blocks onto hyaluronic acid by a click conjugation reaction. The obtained HA-g-PZLLs self-assembled into nanoparticles in the presence of AIE molecules and SPIO nanoparticles to produce tumor-targeted theranostic nanoparticles (SPIO/AIE@HA-g-PZLLs) with MR/FL dual-modal imaging ability. Cellular uptake of the theranostic nanoparticles was traced by confocal laser scanning microscopy (CLSM), flow cytometry and Prussian blue staining. The intracellular reactive oxygen species (ROS) generation characteristics of the theranostic nanoparticles were evaluated with CLSM and flow cytometry. The effect of PDT was evaluated by cytotoxicity assay. The dual-mode imaging ability of the nanoparticles was evaluated by a real-time near-infrared fluorescence imaging system and magnetic resonance imaging scanning. RESULTS: The resulting theranostic nanoparticles not only emit red fluorescence for high-quality intracellular tracing but also effectively produce singlet oxygen for photodynamic tumor therapy. In vitro cytotoxicity experiments showed that these theranostic nanoparticles can be efficiently taken up and are mainly present in the cytoplasm of HepG2 cells. After internalization, these theranostic nanoparticles showed serious cytotoxicity to the growth of HepG2 cells after white light irradiation. DISCUSSION: This work provides a simple method for the preparation of theranostic nanoparticles with AIE characteristics and MR contrast enhancement, and serves as a dual-modal imaging platform for image-guided tumor PDT.


Assuntos
Meios de Contraste/química , Imageamento por Ressonância Magnética , Nanopartículas/química , Imagem Óptica , Fotoquimioterapia , Nanomedicina Teranóstica , Animais , Linhagem Celular Tumoral , Feminino , Fluorescência , Células Hep G2 , Humanos , Ácido Hialurônico/síntese química , Ácido Hialurônico/química , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Polilisina/síntese química , Polilisina/química , Espectroscopia de Prótons por Ressonância Magnética , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
13.
Medicine (Baltimore) ; 99(18): e20093, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358396

RESUMO

Identification of histologic grading of urothelial carcinoma still depends on histopathologic examination. As an emerging and promising imaging technology, radiomic texture analysis is a noninvasive technique and has been studied to differentiate various tumors. This study explored the value of computed tomography (CT) texture analysis for the differentiation of low-grade urothelial carcinoma (LGUC), high-grade urothelial carcinoma (HGUC), and their invasive properties.Radiologic data were analyzed retrospectively for 94 patients with pathologically proven urothelial carcinomas from November 2016 to April 2019. Pathologic examination demonstrated that tumors were: high grade in 43 cases, and low grade in 51 cases; and nonmuscle invasive (NMI) in 37 cases, and muscle invasive (MI) in 37 cases. Maximum tumor diameters on CT scan were manually outlined as regions of interest and 78 texture features were extracted automatically. Three-phasic CT images were used to measure texture parameters, which were compared with postoperative pathologic grading and invasive results. The independent sample t test or Mann-Whitney U test was used to compare differences in parameters. Receiver-operating characteristic curves for statistically significant parameters were used to confirm efficacy.Of the 78 features extracted from each phase of CT images, 26 (33%), 20 (26%), and 22 (28%) texture parameters were significant (P < .05) for differentiating LGUC from HGUC, while 19 (24%), 16 (21%), and 30 (38%) were significant (P < .05) for differentiating NMI from MI urothelial carcinoma. Highest areas the under curve for differentiating grading and invasive properties were obtained by variance (0.761, P < .001) and correlation (0.798, P < .001) on venous-phase CT images.Texture analysis has the potential to distinguish LGUC and HGUC, or NMI from MI urothelial carcinoma, before surgery.


Assuntos
Carcinoma de Células de Transição/patologia , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Neoplasias da Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Curva ROC , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/diagnóstico por imagem
14.
Mater Sci Eng C Mater Biol Appl ; 98: 9-18, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30813097

RESUMO

Tumor-targeted multifunctional nanocarriers play an important role in tumor diagnosis and treatment. Herein, disulfide bonds linked amphiphilic hyaluronan-SS-poly(ε-caprolactone) diblock copolymers (HA-SS-PCL) were synthesized and studied as theranostic nanocarriers for tumor diagnosis and treatment. The chemical structure of HA-SS-PCL was confirmed by Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H NMR). The self-assembling behavior of the HA-SS-PCL into GSH-responsive micelles and their degradation were characterized by fluorescence spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM). Theranostic nanocarriers encapsulating doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) were formed via a dialysis. In vitro drug release results suggested that the HA-SS-PCL micelles possessed reductant-triggered doxorubicin release ability, which was confirmed by 100% of DOX release from HA-SS-PCL micelles within 12 h under 10 mM of glutathione (GSH), whereas about 40% of DOX was released under non-reductive condition within 24 h. Both flow cytometry and confocal laser scanning microscopy (CLSM) analysis revealed that the HA-SS-PCL micelles loaded with DOX were internalized in HepG2 cell via a receptor mediated mechanism between hyaluronan and the CD44 receptor. Furthermore, the MTT assay and cell apoptosis analysis revealed that the DOX-loaded HA-SS-PCL micelles exhibited pronounced antitumor ability towards HepG2 cells compared with that of the reduction-insensitive HA-PCL micelles at the same DOX dosage. The r2 relaxivity value of the DOX/SPIO loaded HA-SS-PCL micelles was up to 221.2 mM-1 s-1 (Fe). Thus, the obtained HA-SS-PCL block copolymers demonstrate promising potential as tumor targeting theranostic nanocarriers in the field of tumor diagnosis and treatment.


Assuntos
Ácido Hialurônico/química , Neoplasias/diagnóstico , Poliésteres/química , Polímeros/química , Nanomedicina Teranóstica/métodos , Animais , Apoptose , Citometria de Fluxo , Células Hep G2 , Humanos , Micelas , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Neoplasias/terapia , Espectrometria de Fluorescência
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 201: 216-222, 2018 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-29753966

RESUMO

A fluorescence probe based on thiosemicarbazide has been synthesized and well characterized by 1H NMR, 13C NMR, Elemental analysis, Electrospray ionization mass spectra. The probe 1 functions as a multitarget ion sensor, detect biologically and ecologically important Cd2+, PO43- and Cr3+. Meanwhile, probe 1 displays selectivity for Cd2+ over other metal ions and anions in DMF by emission spectrum. Interestingly, probe 1 has been explored to recognize PO43- in CH3OH-H2O (v:v = 1:9). The binding stoichiometry of probe 1 with Cd2+ and PO43- are 2:1 and 1:1, respectively, which are confirmed by Electrospray ionization mass spectra. Probe 1 is selective, sensitive and reversibility/reusability to Cd2+ and PO43- with the detection limit as low as 0.035 µM and 0.011 µM respectively. Besides, the designed probe 1 has shown potential applications in the area of photo-printing.

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