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1.
Nanomaterials (Basel) ; 14(17)2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39269100

RESUMEN

Delaying an electromagnetic (EM) wave pulse on a thin screen for a significant time before releasing it is highly desired in many applications, such as optical camouflage, information storage, and wave-matter interaction boosting. However, available approaches to achieve this goal either require thick and complex systems or suffer from low efficiencies and a short delay time. This paper proposes an ultra-thin meta-platform that can significantly delay an EM-wave pulse after reflection. Specifically, our meta-platform consists of three meta-surfaces integrated together, of which two are responsible for efficiently coupling incident EM-wave pulse into surface waves (SWs) and vice versa, and the third one supports SWs exhibiting significantly reduced group velocity. We employ theoretical model analyses, full-wave simulations, and microwave experiments to validate the proposed concept. Our experiments demonstrate a 13 ns delay of an EM pulse centered at 12.975 GHz, enabled by a λ/8-thick and 38-λ-long meta-device with an efficiency of 32% (or 70%) with (or without) material loss taken into account. A larger delay time can be enabled by devices with larger sizes considering that the SWs group velocity of our device can be further reduced via dispersion engineering. These findings establish a new road for delaying an EM-wave pulse with ultra-thin screens, which may lead to many promising applications in integration optics.

2.
J Am Chem Soc ; 145(46): 25086-25092, 2023 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-37948601

RESUMEN

Cyclopamine is a teratogenic steroidal alkaloid, which inhibits the Hedgehog (Hh) signaling pathway by targeting the Smoothened (Smo) receptor. Suppression of Hh signaling with synthetic small molecules has been pursued as a therapeutic approach for the treatment of cancer. We report herein the asymmetric synthesis of cyclopamine based on a two-stage relay strategy. Stage-I: total synthesis of veratramine through a convergent approach, wherein a crucial photoinduced excited-state Nazarov reaction was applied to construct the basic [6-6-5-6] skeleton of C-nor-D-homo-steroid. Stage-II: conversion of veratramine to cyclopamine was achieved through a sequence of chemo-selective redox manipulations.


Asunto(s)
Alcaloides , Antineoplásicos , Proteínas Hedgehog/metabolismo , Transducción de Señal , Antineoplásicos/farmacología , Alcaloides/farmacología , Receptores Acoplados a Proteínas G/metabolismo
3.
Opt Express ; 31(21): 34112-34122, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37859175

RESUMEN

Plasmonic vortices have shown a wide range of applications in on-chip photonics due to their fascinating properties of the orbital angular momenta (OAM) and phase singularity. However, conventional devices to generate them suffer from issues of low efficiencies and limited functionalities. Here, we establish a systematic scheme to construct high-efficiency bifunctional metasurfaces that can generate two plasmonic vortices exhibiting distinct topological charges, based on a series of reflective meta-atoms exhibiting tailored reflection-phases dictated by both resonant and geometric origins. As a benchmark test, we first construct a meta-coupler with meta-atoms exhibiting geometric phases only, and experimentally demonstrate that it can generate a pre-designed plasmonic vortex at the wavelength of 1064 nm with an efficiency of 27% (56% in simulation). Next, we design/fabricate two bifunctional metasurfaces with meta-atoms integrated with both resonant and geometric phases, and experimentally demonstrate that they can generate divergent (or focused) or convergent (or defocused) plasmonic vortices with district OAM as shined by circularly polarized light with opposite helicity at 1064 nm wavelength. Our work provides an efficient platform to generate plasmonic vortices as desired, which can find many applications in on-chip photonics.

4.
Nanoscale Res Lett ; 17(1): 81, 2022 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-36053435

RESUMEN

Metasurface can use artificial microstructures to manipulate electromagnetic waves more accurately and flexibly. All-dielectric metalens have a wide range of materials and low cost so it has a wide application prospect. Herein, we propose a all-dielectric achromatic metalens built with Si as the structural unit that can operate over a broadband of wavelengths in the visible region. It controls the wavefront of light through the Pancharatnam-Berry phase and propagation phase to eliminate the chromatic aberration. Meanwhile, we also use Gerchberg-Saxton algorithm and its improved algorithm to iterate over multiple design wavelengths and obtain holographic phases suitable for broadband. Thus, both the metalenses and holographic metasurfaces can achieve achromatic broadband in the visible light range, which provides a new method for the development of meta-optical imaging devices.

5.
Cancer Biomark ; 32(4): 541-550, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34334383

RESUMEN

BACKGROUND: Patients with advanced pancreatic cancer (APC) and liver metastases have much poorer prognoses than patients with other metastatic patterns. OBJECTIVE: This study aimed to develop and validate a radiomics model to discriminate patients with pancreatic cancer and liver metastases from those with other metastatic patterns. METHODS: We evaluated 77 patients who had APC and performed texture analysis on the region of interest. 58 patients and 19 patients were allocated randomly into the training and validation cohorts with almost the same proportion of liver metastases. An independentsamples t-test was used for feature selection in the training cohort. Random forest classifier was used to construct models based on these features and a radiomics signature (RS) was derived. A nomogram was constructed based on RS and CA19-9, and was validated with calibration plot and decision curve. The prognostic value of RS was evaluated by Kaplan-Meier methods. RESULTS: The constructed nomogram demonstrated good discrimination in the training (AUC = 0.93) and validation (AUC = 0.81) cohorts. In both cohorts, patients with RS > 0.61 had much poorer overall survival than patients with RS < 0.61. CONCLUSIONS: This study presents a radiomics nomogram incorporating RS and CA19-9 to discriminate patients who have APC with liver metastases from patients with other metastatic patterns.


Asunto(s)
Neoplasias Hepáticas/secundario , Neoplasias Pancreáticas/complicaciones , Radiometría/métodos , Anciano , Femenino , Humanos , Masculino , Metástasis de la Neoplasia , Nomogramas , Pronóstico
6.
J Cancer ; 12(8): 2351-2358, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33758611

RESUMEN

Objective: The purpose of this study was to evaluate the prognostic value of computed tomography (CT) texture features of pancreatic cancer with liver metastases. Methods: We included 39 patients with metastatic pancreatic cancer (MPC) with liver metastases and performed texture analysis on primary tumors and metastases. The correlations between texture parameters were assessed using Pearson's correlation. Univariate Cox proportional hazards model was used to assess the correlations between clinicopathological characteristics, texture features and overall survival (OS). The univariate Cox regression model revealed four texture features potentially correlated with OS (P<0.1). A radiomics score (RS) was determined using a sequential combination of four texture features with potential prognostic value that were weighted according to their ß-coefficients. Furthermore, all variables with P<0.1 were included in the multivariate analysis. A nomogram,which was developed to predict OS according to independent prognostic factors, was internally validated using the C-index and calibration plots. Kaplan-Meier analysis and the log-rank test were performed to stratify OS according to the RS and nomogram total points (NTP). Results: Few significant correlations were found between texture features of primary tumors and those of liver metastases. However, texture features within primary tumors or liver metastases were significantly associated. Multivariate analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), chemotherapy, Carbohydrate antigen 19-9 (CA19-9), and the RS were independent prognostic factors (P<0.05). The nomogram incorporating these factors showed good discriminative ability (C-index = 0.754). RS and NTP stratified patients into two potential risk groups (P<0.01). Conclusion: The RS derived from significant texture features of primary tumors and metastases shows promise as a prognostic biomarker of OS of patients with MPC. A nomogram based on the RS and other independent prognostic clinicopathological factors accurately predicts OS.

7.
J Biol Chem ; 295(16): 5427-5448, 2020 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-32165498

RESUMEN

Prevention of aberrant cutaneous wound repair and appropriate regeneration of an intact and functional integument require the coordinated timing of fibroblast and keratinocyte migration. Here, we identified a mechanism whereby opposing cell-specific motogenic functions of a multifunctional intracellular and extracellular protein, the receptor for hyaluronan-mediated motility (RHAMM), coordinates fibroblast and keratinocyte migration speed and ensures appropriate timing of excisional wound closure. We found that, unlike in WT mice, in Rhamm-null mice, keratinocyte migration initiates prematurely in the excisional wounds, resulting in wounds that have re-surfaced before the formation of normal granulation tissue, leading to a defective epidermal architecture. We also noted aberrant keratinocyte and fibroblast migration in the Rhamm-null mice, indicating that RHAMM suppresses keratinocyte motility but increases fibroblast motility. This cell context-dependent effect resulted from cell-specific regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) activation and expression of a RHAMM target gene encoding matrix metalloprotease 9 (MMP-9). In fibroblasts, RHAMM promoted ERK1/2 activation and MMP-9 expression, whereas in keratinocytes, RHAMM suppressed these activities. In keratinocytes, loss of RHAMM function or expression promoted epidermal growth factor receptor-regulated MMP-9 expression via ERK1/2, which resulted in cleavage of the ectodomain of the RHAMM partner protein CD44 and thereby increased keratinocyte motility. These results identify RHAMM as a key factor that integrates the timing of wound repair by controlling cell migration.


Asunto(s)
Proteínas de la Matriz Extracelular/metabolismo , Receptores de Hialuranos/metabolismo , Repitelización , Animales , Línea Celular , Movimiento Celular , Células Cultivadas , Proteínas de la Matriz Extracelular/genética , Fibroblastos/metabolismo , Fibroblastos/fisiología , Receptores de Hialuranos/genética , Queratinocitos/metabolismo , Queratinocitos/fisiología , Sistema de Señalización de MAP Quinasas , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo
8.
Plast Reconstr Surg ; 145(1): 116-126, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31881612

RESUMEN

BACKGROUND: Radiofibrosis of breast tissue compromises breast reconstruction by interfering with tissue viability and healing. Autologous fat transfer may reduce radiotherapy-related tissue injury, but graft survival is compromised by the fibrotic microenvironment. Elevated expression of receptor for hyaluronan-mediated motility (RHAMM; also known as hyaluronan-mediated motility receptor, or HMMR) in wounds decreases adipogenesis and increases fibrosis. The authors therefore developed RHAMM peptide mimetics to block RHAMM profibrotic signaling following radiation. They propose that this blocking peptide will decrease radiofibrosis and establish a microenvironment favoring adipose-derived stem cell survival using a rat mammary fat pad model. METHODS: Rat mammary fat pads underwent a one-time radiation dose of 26 Gy. Irradiated (n = 10) and nonirradiated (n = 10) fat pads received a single intramammary injection of a sham injection or peptide NPI-110. Skin changes were examined clinically. Mammary fat pad tissue was processed for fibrotic and adipogenic markers using quantitative polymerase chain reaction and immunohistochemical analysis. RESULTS: Clinical assessments and molecular analysis confirmed radiation-induced acute skin changes and radiation-induced fibrosis in rat mammary fat pads. Peptide treatment reduced fibrosis, as detected by polarized microscopy of picrosirius red staining, increased collagen ratio of 3:1, reduced expression of collagen-1 crosslinking enzymes lysyl-oxidase, transglutaminase 2, and transforming growth factor ß1 protein, and increased adiponectin, an antifibrotic adipokine. RHAMM was expressed in stromal cell subsets and was downregulated by the RHAMM peptide mimetic. CONCLUSION: Results from this study predict that blocking RHAMM function in stromal cell subsets can provide a postradiotherapy microenvironment more suitable for fat grafting and breast reconstruction.


Asunto(s)
Tejido Adiposo/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Fibrosis/metabolismo , Receptores de Hialuranos/metabolismo , Traumatismos Experimentales por Radiación/metabolismo , Adipogénesis/efectos de los fármacos , Adipogénesis/fisiología , Animales , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Fibrosis/tratamiento farmacológico , Péptidos/farmacología , Proteína Glutamina Gamma Glutamiltransferasa 2
9.
Front Immunol ; 10: 947, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31134064

RESUMEN

Hyaluronan (HA) is a glycosaminoglycan with a simple structure but diverse and often opposing functions. The biological activities of this polysaccharide depend on its molecular weight and the identity of interacting receptors. HA is initially synthesized as high molecular-weight (HMW) polymers, which maintain homeostasis and restrain cell proliferation and migration in normal tissues. These HMW-HA functions are mediated by constitutively expressed receptors including CD44, LYVE-1, and STABILIN2. During normal processes such as tissue remodeling and wound healing, HMW-HA is fragmented into low molecular weight polymers (LMW-HA) by hyaluronidases and free radicals, which promote inflammation, immune cell recruitment and the epithelial cell migration. These functions are mediated by RHAMM and TLR2,4, which coordinate signaling with CD44 and other HA receptors. Tumor cells hijack the normally tightly regulated HA production/fragmentation associated with wound repair/remodeling, and these HA functions participate in driving and maintaining malignant progression. However, elevated HMW-HA production in the absence of fragmentation is linked to cancer resistance. The controlled production of HA polymer sizes and their functions are predicted to be key to dissecting the role of microenvironment in permitting or restraining the oncogenic potential of tissues. This review focuses on the dual nature of HA in cancer initiation vs. resistance, and the therapeutic potential of HA for chemo-prevention and as a target for cancer management.


Asunto(s)
Ácido Hialurónico/metabolismo , Neoplasias/metabolismo , Microambiente Tumoral , Animales , Humanos , Receptores de Hialuranos/metabolismo , Hialuronoglucosaminidasa/metabolismo
10.
Nanomedicine ; 14(1): 205-213, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29045825

RESUMEN

Apoptosis imaging enables a timely and specific assessment of treatment response in cancer patients. In this study, we applied a probe for positron emission tomography (PET), which served as an optical biomaterial emitting Cerenkov photons, to in vivo optical imaging of tumor apoptosis, in order to evaluate early response to chemotherapy of drug-resistant gastric cancer. 68Ga-DOTA-Annexin V was prepared as the apoptosis targeting probe. Wild type human gastric adenocarcinoma cell line SGC7901/WT and drug vincristine-resistant variant SGC7901/VCR were used to establish normal and vincristine-resistant xenografts to simulate treatment decision situation. Vincristine-resistance of SGC7901/VCR and apoptosis-induction ability of vincristine and cisplatin were verified. In vitro and in vivo CLI of apoptosis was performed. Stronger signals of apoptosis of CLI correlated with confirmed higher levels of apoptosis and subsequent changes in tumor sizes. Our study suggests that CLI is a promising technique for in vivo imaging of apoptosis with radiopharmaceutical-labeled biomaterials.


Asunto(s)
Apoptosis/efectos de los fármacos , Cisplatino/farmacología , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Neoplasias Gástricas/patología , Vincristina/farmacología , Animales , Antineoplásicos/farmacología , Antineoplásicos Fitogénicos/farmacología , Femenino , Radioisótopos de Galio/metabolismo , Humanos , Luminiscencia , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Tomografía de Emisión de Positrones/métodos , Radiofármacos/metabolismo , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Biomed Opt Express ; 8(3): 1356-1371, 2017 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-28663833

RESUMEN

Multimodality molecular imaging emerges as a powerful strategy for correlating multimodal information. We developed a pentamodal imaging system which can perform positron emission tomography, bioluminescence tomography, fluorescence molecular tomography, Cerenkov luminescence tomography and X-ray computed tomography successively. Performance of sub-systems corresponding to different modalities were characterized. In vivo multimodal imaging of an orthotopic hepatocellular carcinoma xenograft mouse model was performed, and acquired multimodal images were fused. The feasibility of pentamodal tomographic imaging system was successfully validated with the imaging application on the mouse model. The ability of integrating anatomical, metabolic, and pharmacokinetic information promises applications of multimodality molecular imaging in precise medicine.

12.
Nanomedicine ; 13(4): 1323-1331, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28115248

RESUMEN

Fluorescent molecular imaging technique has been actively explored for optical image-guided cancer surgery in pre-clinical and clinical research and has attracted many attentions. However, the efficacy of the fluorescent image-guided cancer surgery can be compromised by the low signal-to-noise ratio caused by the external light excitation. This study presents a novel nanoparticle-mediated radiopharmaceutical-excited fluorescent (REF) image-guided cancer surgery strategy, which employs the internal dual-excitation of europium oxide nanoparticles through both gamma rays and Cerenkov luminescence emitted from radiopharmaceuticals. The performance of the novel image-guided surgery technique was systematically evaluated using subcutaneous breast cancer 4 T1 tumor models, orthotropic and orthotropic-ectopic hepatocellular carcinoma tumor-bearing mice. The results reveal that the novel REF image-guided cancer surgery technique exhibits high performance of detecting invisible ultra-small size tumor (even less than 1 mm) and residual tumor tissue. Our study demonstrates the high potential of the novel image-guided cancer surgery for precise tumor resection.


Asunto(s)
Neoplasias de la Mama/cirugía , Neoplasias Hepáticas/cirugía , Imagen Molecular , Nanopartículas/química , Radiofármacos/química , Cirugía Asistida por Computador , Animales , Línea Celular Tumoral , Fluorescencia , Humanos , Ratones , Trasplante de Neoplasias
13.
J Nucl Med ; 58(1): 169-174, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27660137

RESUMEN

Cerenkov luminescence imaging can image radiopharmaceuticals using a high-sensitivity charge-coupled device camera. However, Cerenkov luminescence emitted from the radiopharmaceuticals is weak and has low penetration depth in biologic tissues, which severely limits the sensitivity and accuracy of Cerenkov luminescence imaging. This study presents 3-dimensional (3D) radiopharmaceutical-excited fluorescence tomography (REFT) using europium oxide (EO) nanoparticles, which enhances the Cerenkov luminescence signal intensity, improves the penetration depth, and obtains more accurate 3D distribution of radiopharmaceuticals. METHODS: The enhanced optical signals of various radiopharmaceuticals (including Na131I, 18F-FDG, 68GaCl3, Na99mTcO4) by EO nanoparticles were detected in vitro. The location and 3D distribution of the radiopharmaceuticals of REFT were then reconstructed and compared with those of Cerenkov luminescence tomography through the experiments with the phantom, artificial source-implanted mouse models, and mice bearing hepatocellular carcinomas. RESULTS: The mixture of 68GaCl3 and EO nanoparticles possessed the strongest optical signals compared with the other mixtures. The in vitro phantom and implanted mouse studies showed that REFT revealed more accurate 3D distribution of 68GaCl3 REFT can detect more tumors than small-animal PET in hepatocellular carcinoma-bearing mice and achieved more accurate 3D distribution information than Cerenkov luminescence tomography. CONCLUSION: REFT with EO nanoparticles significantly improves accuracy of localization of radiopharmaceuticals and can precisely localize the tumor in vivo.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico por imagen , Imagenología Tridimensional/métodos , Microscopía Fluorescente/métodos , Imagen Molecular/métodos , Tomografía de Emisión de Positrones/métodos , Radiofármacos/análisis , Animales , Carcinoma Hepatocelular/química , Línea Celular Tumoral , Aumento de la Imagen/métodos , Masculino , Nanopartículas del Metal/análisis , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Microscopía Fluorescente/instrumentación , Imagen Molecular/instrumentación , Fantasmas de Imagen , Tomografía de Emisión de Positrones/instrumentación , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tomografía Óptica/instrumentación , Tomografía Óptica/métodos , Imagen de Cuerpo Entero/instrumentación , Imagen de Cuerpo Entero/métodos
14.
IEEE Trans Med Imaging ; 35(12): 2546-2557, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27352391

RESUMEN

The computation of model matrix in the iterative imaging reconstruction process is crucial for the quantitative photoacoustic tomography (PAT). However, it is challenging to establish an outstanding model matrix to improve the overall imaging quality in PAT due to the noisy signal acquisition and inevitable artifacts. In this work, we present a novel method, named as the curve-driven-based model-matrix inversion (CDMMI), to calculate the model matrix for tomographic reconstruction in photoacoustic imaging. It eliminated the use of interpolation techniques, and thus avoided all interpolation related errors. The conventional interpolated-matrix-model inversion (IMMI) method was applied to evaluate its performance in numerical simulation, tissue-mimicking phantom and in vivo small animal studies. Results demonstrated that CDMMI achieved better reconstruction accuracy until IMMI kept increasing discrete points to 10000. Furthermore, the proposed method can suppress the negative influence of noise and artifacts effectively, which benefited the overall imaging quality of photoacoustic tomography.


Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Técnicas Fotoacústicas/métodos , Tomografía/métodos , Algoritmos , Animales , Simulación por Computador , Riñón/diagnóstico por imagen , Ratones , Fantasmas de Imagen , Relación Señal-Ruido
15.
BMC Cancer ; 15: 358, 2015 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-25943993

RESUMEN

BACKGROUND: Multidrug resistance (MDR) is a major obstacle to the treatment of gastric cancer (GC). Using a phage display approach, we previously obtained the peptide GMBP1, which specifically binds to the surface of MDR gastric cancer cells and is subsequently internalized. Furthermore, GMBP1 was shown to have the potential to reverse the MDR phenotype of gastric cancer cells, and GRP78 was identified as the receptor for this peptide. The present study aimed to investigate the mechanism of peptide GMBP1 and its receptor GRP78 in modulating gastric cancer MDR. METHODS: Fluorescence-activated cell sorting (FACS) and immunofluorescence staining were used to investigate the subcellular location and mechanism of GMBP1 internalization. iTRAQ was used to identify the MDR-associated downstream targets of GMBP1. Differentially expressed proteins were identified in GMBP1-treated compared to untreated SGC7901/ADR and SGC7901/VCR cells. GO and KEGG pathway analyses of the differentially expressed proteins revealed the interconnection of these proteins, the majority of which are involved in MDR. Two differentially expressed proteins were selected and validated by western blotting. RESULTS: GMBP1 and its receptor GRP78 were found to be localized in the cytoplasm of GC cells, and GRP78 can mediate the internalization of GMBP1 into MDR cells through the transferrin-related pathway. In total, 3,752 and 3,749 proteins were affected in GMBP1-treated SGC7901/ADR and SGC7901/VCR cells, respectively, involving 38 and 79 KEGG pathways. Two differentially expressed proteins, CTBP2 and EIF4E, were selected and validated by western blotting. CONCLUSION: This study explored the role and downstream mechanism of GMBP1 in GC MDR, providing insight into the role of endoplasmic reticulum stress protein GRP78 in the MDR of cancer cells.


Asunto(s)
Antinematodos/farmacología , Resistencia a Antineoplásicos , Proteínas de Choque Térmico/metabolismo , Oligopéptidos/farmacología , Doxorrubicina/farmacología , Resistencia a Múltiples Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Sinergismo Farmacológico , Chaperón BiP del Retículo Endoplásmico , Humanos , Transporte de Proteínas , Proteoma/metabolismo , Neoplasias Gástricas , Vincristina/farmacología
16.
Carcinogenesis ; 36(3): 390-9, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25653235

RESUMEN

MicroRNAs (miRNAs) are thought to have an important role in tumor metastasis by regulating diverse cellular pathways. Here, we describe the function and regulation network of miR-206 in gastric cancer (GC) metastasis. MiR-206 expression was downregulated in GC cells especially in high metastatic potential cells and was also significantly decreased in metastatic lesions compared with their corresponding primary tumor samples. Both gain- and loss-of-function studies confirmed that miR-206 significantly suppressed GC cell invasion and metastasis both in vitro and in vivo. Mechanistically, paired box gene 3 (PAX3) was identified as a functional target of miR-206 in GC cells. MiR-206 inhibited GC metastasis by negatively regulating expression of PAX3. In addition, PAX3 expression was markedly higher in GC tissues than in adjacent non-cancerous tissues. GC patients with positive PAX3 expression had shorter overall survival times. Transwell assays and in vivo metastasis assays demonstrated that overexpression of PAX3 significantly promoted the invasiveness and pulmonary metastasis of GC cells. On the other hand, downregulation of PAX3 markedly reduced cell metastatic potential. Mechanistic investigations indicated that prometastasis function of PAX3 was mediated by upregulating downstream target MET. Moreover, we found that levels of PAX3 and MET were positively correlated in matched human GC specimens, and their coexpression was associated with poor prognoses. In conclusion, our results reveal that miR-206-PAX3-MET signaling is critical to GC metastasis. Targeting the pathway described here may open new therapeutic prospects to restrict the metastatic potential of GC.


Asunto(s)
MicroARNs/genética , Factores de Transcripción Paired Box/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Animales , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/metabolismo , Factor de Transcripción PAX3 , Factores de Transcripción Paired Box/genética , Pronóstico , Proteínas Proto-Oncogénicas c-met/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad
17.
ACS Nano ; 9(2): 2120-9, 2015 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-25602117

RESUMEN

Lymphatic metastasis is an important prognostic factor regarding long-term survival rate of gastric cancer (GC) patients. Pretreatment knowledge of lymph node status is extremely helpful for planning treatment and prognosis. However, to date, no imaging method has been demonstrated to be effective for detecting lymphatic metastasis in GC. Molecular imaging probes based on upconversion nanoparticles with unique optical and magnetic properties have provided great hope for early tumor detection. Herein we report highly sensitive detection of lymphatic spread using core@shell structured NaGdF4:Yb,Er@NaGdF4 upconversion nanoparticles coated with polyethylene glycol (PEG). A GC-specific probe was constructed through "click" reaction between the maleimide moiety of PEG ligand and the thiol group from partly reduced antigastric cancer antibody MGb2. The primary tumor and adjacent lymphatic metastasis site were clearly differentiated by upconversion luminescence imaging after the GC-specific probe was delivered through tail vein injection into tumor-bearing mice. Moreover, lymphatic metastases smaller than 1 mm were successfully detected, owing to the ultralow background under 980 nm excitation. It has been demonstrated that both primary and lymphatic metastatic sites in an orthotopic mouse model of human gastric cancer can be optically detected by using GC-specific upconversion luminescence nanoprobes. The current studies may therefore provide a highly effective approach for GC diagnosis.


Asunto(s)
Imagen Molecular/métodos , Sondas Moleculares/química , Nanopartículas/química , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Animales , Línea Celular Tumoral , Transformación Celular Neoplásica , Erbio/química , Femenino , Fluoruros/química , Humanos , Luminiscencia , Metástasis Linfática , Ratones , Sondas Moleculares/metabolismo , Imagen Óptica , Polietilenglicoles/química , Sensibilidad y Especificidad , Iterbio/química
18.
Eur Radiol ; 25(6): 1814-22, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25577521

RESUMEN

OBJECTIVES: Cerenkov luminescence imaging (CLI) provides potential to use clinical radiotracers for optical imaging. The goal of this study was to present a newly developed endoscopic CLI (ECLI) system and illustrate its feasibility and potential in distinguishing and quantifying cancerous lesions of the GI tract. METHODS: The ECLI system was established by integrating an electron-multiplying charge-coupled device camera with a flexible fibre endoscope. Phantom experiments and animal studies were conducted to test and illustrate the system in detecting and quantifying the presence of radionuclide in vitro and in vivo. A pilot clinical study was performed to evaluate our system in clinical settings. RESULTS: Phantom and mice experiments demonstrated its ability to acquire both the luminescent and photographic images with high accuracy. Linear quantitative relationships were also obtained when comparing the ECLI radiance with the radiotracer activity (r (2) = 0.9779) and traditional CLI values (r (2) = 0.9025). Imaging of patients revealed the potential of ECLI in the identification and quantification of cancerous tissue from normal, which showed good consistence with the clinical PET examination. CONCLUSIONS: The new ECLI system shows good consistence with the clinical PET examination and has great potential for clinical translation and in aiding detection of the GI tract disease. KEY POINTS: • CLI preserves the characteristics of both optical and radionuclide imaging. • CLI provides great potential for clinical translation of optical imaging. • The newly developed endoscopic CLI (ECLI) has quantification and imaging capacities. • GI tract has accessible open surfaces, making ECLI a potentially suitable technique. • Cerenkov endoscopy has great clinical potential in detecting GI disease.


Asunto(s)
Luminiscencia , Proctoscopía/métodos , Neoplasias del Recto/diagnóstico , Adulto , Animales , Estudios de Factibilidad , Femenino , Fluorodesoxiglucosa F18/administración & dosificación , Humanos , Masculino , Ratones Desnudos , Persona de Mediana Edad , Neoplasias/diagnóstico , Fantasmas de Imagen , Proyectos Piloto , Tomografía de Emisión de Positrones/métodos , Radiofármacos/administración & dosificación
19.
Ann Surg Oncol ; 22(2): 685-92, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24809300

RESUMEN

BACKGROUND: FOXJ1 is a member of the forkhead transcription factor family, which has been mostly studied for its role in the development of ciliated epithelium and immunology. However, the role of FOXJ1 in tumorigenesis remains largely unknown or even conflicting. We thus investigated FOXJ1 expression in gastric cancer and analyzed its correlations with tumor progression and prognosis. METHODS: The expression of FOXJ1 was detected by immunohistochemistry in 105 gastric cancer samples and adjacent noncancerous tissues. Staining evaluation was conducted to assess clinicopathological parameters and the survival rate. In addition, the relation between FOXJ1 and metastasis was investigated in another 40 pairs of primary lesions and corresponding lymph node metastases. Furthermore, cell proliferation, migration, and invasion were confirmed in vitro. RESULTS: Decreased FOXJ1 expression was significantly correlated with clinic stage, lymph node metastasis, and distant metastasis, and lower FOXJ1 expression independently predicted shorter survival time in gastric carcinoma. Moreover, the positive incidence of FOXJ1 decreased significantly in metastatic lymph nodes compared with that in the primary lesions. Consistently, FOXJ1 overexpression significantly weakened cell proliferation, motility, migration, and invasion, while FOXJ1 knockdown induced the opposite effects. CONCLUSIONS: Decreased expression of FOXJ1 is an independent prognostic predictor for gastric cancer and is critical to disease progression. FOXJ1 may be an attractive therapeutic target for the treatment of gastric cancer.


Asunto(s)
Adenocarcinoma/genética , Factores de Transcripción Forkhead/biosíntesis , Neoplasias Gástricas/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Factores de Transcripción Forkhead/genética , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Análisis de Supervivencia , Análisis de Matrices Tisulares
20.
Biomed Opt Express ; 5(10): 3660-70, 2014 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-25360380

RESUMEN

By integrating the clinically used endoscope with the emerging Cerenkov luminescence imaging (CLI) technology, a new endoscopic Cerenkov luminescence imaging (ECLI) system was developed. The aim is to demonstrate the potential of translating CLI to clinical studies of gastrointestinal (GI) tract diseases. We systematically evaluated the feasibility and performance of the developed ECLI system with a series of in vitro and pseudotumor experiments. The ECLI system is comprised of an electron multiplying charge coupled device (EMCCD) camera coupled with a clinically used endoscope via an optical adapter. A 1951-USAF test board was used to measure the white-light lateral resolution, while a homemade test chart filled with (68)Ga was employed to measure the CL lateral resolution. Both in vitro and pseudotumor experiments were conducted to obtain the sensitivity of the ECLI system. The results were validated with that of CLI using EMCCD only, and the relative attenuation ratio of the ECLI system was calculated. Results showed that The white-light lateral resolution of the ECLI system was 198 µm, and the luminescent lateral resolution was better than 1 mm. Sensitivity experiments showed a theoretical sensitivity of [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]) for the in vitro and pseudotumor studies, respectively. The relative attenuation ratio of ECLI to CLI was about 96%. The luminescent lateral resolution of the ECLI system was comparable with that of positron emission tomography (PET). The pseudotumor study illustrated the feasibility and applicability of the ECLI system in living organisms, indicating the potential for translating the CLI technology to the clinic.

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