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1.
Adv Mater ; 36(15): e2310818, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38190432

RESUMO

Tumor calcification is found to be associated with the benign prognostic, and which shows considerable promise as a somewhat predictive index of the tumor response clinically. However, calcification is still a missing area in clinical cancer treatment. A specific strategy is proposed for inducing tumor calcification through the synergy of calcium peroxide (CaO2)-based microspheres and transcatheter arterial embolization for the treatment of hepatocellular carcinoma (HCC). The persistent calcium stress in situ specifically leads to powerful tumor calcioptosis, resulting in diffuse calcification and a high-density shadow on computed tomography that enables clear localization of the in vivo tumor site and partial delineation of tumor margins in an orthotopic HCC rabbit model. This osmotic calcification can facilitate tumor clinical diagnosis, which is of great significance in differentiating tumor response during early follow-up periods. Proteome and phosphoproteome analysis identify that calreticulin (CALR) is a crucial target protein involved in tumor calcioptosis. Further fluorescence molecular imaging analysis also indicates that CALR can be used as a prodromal marker of calcification to predict tumor response at an earlier stage in different preclinical rodent models. These findings suggest that upregulated CALR in association with tumor calcification, which may be broadly useful for quick visualization of tumor response.


Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Animais , Coelhos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Detecção Precoce de Câncer , Microesferas
2.
Bioeng Transl Med ; 8(2): e10404, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36925696

RESUMO

The clinical applications of transcatheter arterial embolization (TAE) conversion therapy combined with hepatectomy have been severely restricted by ill-defined tumoral boundaries and miniscule hidden lesions. Fluorescent surgical navigation is a promising method for overcoming these barriers. However, sufficient delivery of the fluorescent probe into the tumor region after long-term TAE is challenging due to blockade of the tumor-supplying artery. Here, a super-stable homogeneous intermix formulating technology (SHIFT) to physically mix lipiodol and indocyanine green (ICG) formulation (SHIFT and ICG) for fluorescent surgical navigation after long-term TAE conversion therapy is provided. Through the retrospective study of 45 clinical liver cancer patients, it is found that SHIFT and ICG formulation have excellent tumor deposition effect and safety. During surgical resection after long-term TAE conversion therapy, SHIFT and ICG could clearly identify in real time the full tumor regions and boundaries and had a high signal-to-normal tissues ratio-even the indistinguishable satellite lesions could be identified with a strong fluorescence intensity. Meanwhile, SHIFT and ICG could improve operative, anesthetic, and postoperative variables associated with postoperative complications. This simple and effective SHIFT could provide precise fluorescent navigation for surgical resection following long-term embolization therapy in clinical practice and has great potential for a translational pipeline.

3.
Eur J Nucl Med Mol Imaging ; 50(4): 1205-1215, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36495325

RESUMO

PURPOSE: This study aimed to assess the diagnostic performance of [18F]FAPI-42 PET/CT and compare it with that of 2-[18F]FDG PET/CT in patients with differentiated thyroid cancer (DTC) with biochemical elevations in Tg or anti-Tg antibodies. METHODS: A total of 42 patients with DTC with biochemical elevations in Tg or anti-Tg antibodies underwent [18F]FAPI-42 PET/CT as part of this study; of which, 11 additionally underwent 2-[18F]FDG PET/CT within 7 days. Images were semi-quantitatively and visually interpreted, and the quantity, location, and uptake values of lesions were noted. The diagnostic capacity of [18F]FAPI-42 PET/CT and biomarkers affecting the uptake of [18F]FAPI-42 were evaluated. In addition, the diagnostic performance and uptake of [18F]FAPI-42 and 2-[18F]FDG were compared, and the correlation between lesion diameter and quantitative parameters was investigated. RESULTS: A total of 161 lesions were detected in 27 (64%) patients on [18F]FAPI-42 PET/CT. FAPI-positive local recurrence showed the highest uptake intensity, followed by lymphatic, other site-associated (bone and pleura), and pulmonary lesions (mean SUVmax, 4.7 versus 3.7 versus 3.0 versus 2.2, respectively; P < 0.0001). The levels of TSH, Tg, and Tg-Ab did not affect the uptake value of lesions (median SUVmax: 2.4 versus 3.2, P = 0.56; 2.9 versus 2.4, P = 0.0935; 2.8 versus 2.6, P = 0.0525, respectively). A total of 90 positive lesions were detected in 7 patients using both modalities. All positive lesions showed statistically higher uptake of 2-[18F]FDG than that of [18F]FAPI-42 (SUVmax, 2.6 versus 2.1; P = 0.026). However, the SUVmax of [18F]FAPI-42 was higher than that of 2-[18F]FDG in local recurrences and lymphatic lesions (SUVmax, 4.2 versus 2.9 and 3.9 versus 3.4, respectively; P > 0.05). CONCLUSION: [18F]FAPI-42 can be used for detecting lesions and reflecting FAP expression during local recurrence and metastasis in patients with DTC with biochemical elevations in Tg or anti-Tg antibodies. The diagnostic performance of [18F]FAPI-42 PET/CT is comparable with that of 2-[18F]FDG PET/CT in such patients.


Assuntos
Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Tomografia por Emissão de Pósitrons , Radioisótopos de Gálio
4.
ACS Biomater Sci Eng ; 8(10): 4535-4546, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36070516

RESUMO

In nonsmall cell lung cancers (NSCLC), near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has proven to be an efficient approach for locating pulmonary nodules and pulmonary sentinel lymph nodes. However, due to a lack of tumor selectivity, ICG's use as a photosensitizer for photothermal therapy (PTT) and photodynamic therapy (PDT) is restricted. In the current study, we aimed to develop a type of high-performance NIR nanoparticle formulated with ICG to enhance its targeted efficacy and tumor specificity on NSCLC. An ICG-osimertinib nanoparticle (ICG-Osi) was self-assembled through π-π stacking, with a size of 276 nm and a surface charge of -7.4 mV. The NIR visibility and epidermal growth factor receptor (EGFR) targetability of the ICG-Osi was confirmed by its binding efficiency to EGFR-expressing NSCLC cells in vitro and in vivo, regardless of EGFR mutation status. The targeted effect was further confirmed in mouse xenograft models and showed an extended tumor retention time (>96 h). We demonstrated a significantly enhanced hyperthermia effect and a retained reactive oxygen species (ROS) generating ability of ICG-Osi, resulting in a 2-fold higher cell death rate than ICG alone. The ICG-Osi down-regulated GPX4 and p62 expression while up-regulating caspase-3 and beclin1 expression in NSCLC cells, indicating a complex network of cell death-related proteins. Considering the merits of simple assembly, EGFR binding efficacy, improved hyperthermia effect, and efficient cancer cell suppression, the ICG-Osi exhibits great potential for clinical application in EGFR-expressing NSCLC therapy.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Animais , Proteína Beclina-1 , Caspase 3 , Receptores ErbB/genética , Humanos , Verde de Indocianina/farmacologia , Verde de Indocianina/uso terapêutico , Camundongos , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
5.
Front Oncol ; 12: 953934, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35957903

RESUMO

Optical coherence tomography (OCT) is a non-invasive imaging technique which has become the "gold standard" for diagnosis in the field of ophthalmology. However, in contrast to the eye, nontransparent tissues exhibit a high degree of optical scattering and absorption, resulting in a limited OCT imaging depth. And the progress made in the past decade in OCT technology have made it possible to image nontransparent tissues with high spatial resolution at large (up to 2mm) imaging depth. On the one hand, OCT can be used in a rapid, noninvasive way to detect diseased tissues, organs, blood vessels or glands. On the other hand, it can also identify the optical characteristics of suspicious parts in the early stage of the disease, which is of great significance for the early diagnosis of tumor diseases. Furthermore, OCT imaging has been explored for imaging tumor cells and their dynamics, and for the monitoring of tumor responses to treatments. This review summarizes the recent advances in the OCT area, which application in oncological diagnosis and treatment in different types: (1) superficial tumors:OCT could detect microscopic information on the skin's surface at high resolution and has been demonstrated to help diagnose common skin cancers; (2) gastrointestinal tumors: OCT can be integrated into small probes and catheters to image the structure of the stomach wall, enabling the diagnosis and differentiation of gastrointestinal tumors and inflammation; (3) deep tumors: with the rapid development of OCT imaging technology, it has shown great potential in the diagnosis of deep tumors such in brain tumors, breast cancer, bladder cancer, and lung cancer.

7.
J Nanobiotechnology ; 20(1): 250, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35658966

RESUMO

BACKGROUND: Applying traditional fluorescence navigation technologies in hepatocellular carcinoma is severely restricted by high false-positive rates, variable tumor differentiation, and unstable fluorescence performance. RESULTS: In this study, a green, economical and safe nanomedicine formulation technology was developed to construct carrier-free indocyanine green nanoparticles (nanoICG) with a small uniform size and better fluorescent properties without any molecular structure changes compared to the ICG molecule. Subsequently, nanoICG dispersed into lipiodol via a super-stable homogeneous intermixed formulation technology (SHIFT&nanoICG) for transhepatic arterial embolization combined with fluorescent laparoscopic hepatectomy to eliminate the existing shortcomings. A 52-year-old liver cancer patient was recruited for the clinical trial of SHIFT&nanoICG. We demonstrate that SHIFT&nanoICG could accurately identify and mark the lesion with excellent stability, embolism, optical imaging performance, and higher tumor-to-normal tissue ratio, especially in the detection of the microsatellite lesions (0.4 × 0.3 cm), which could not be detected by preoperative imaging, to realize a complete resection of hepatocellular carcinoma under fluorescence laparoscopy in a shorter period (within 2 h) and with less intraoperative blood loss (50 mL). CONCLUSIONS: This simple and effective strategy integrates the diagnosis and treatment of hepatocellular carcinoma, and thus, it has great potential in various clinical applications.


Assuntos
Carcinoma Hepatocelular , Laparoscopia , Neoplasias Hepáticas , Nanopartículas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Corantes , Óleo Etiodado , Humanos , Verde de Indocianina , Laparoscopia/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Imagem Óptica/métodos
9.
Quant Imaging Med Surg ; 12(4): 2552-2574, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35371939

RESUMO

Vascular interventional doctors are exposed to radiation hazards during surgery and endure high work intensity. Remote vascular interventional surgery robotics is a hot research field, in which researchers aim to not only protect the health of interventional doctors, but to also improve surgical accuracy and efficiency. However, the current vascular interventional robots have numerous shortcomings, such as poor haptic feedback, few compatible surgeries and instruments, and cumbersome maintenance and operational procedures. Nevertheless, vascular interventional surgery combined with robotics provides more cutting-edge directions, such as Internet remote surgery combined with 5G network technology and the application of artificial intelligence in surgical procedures. To summarize the developmental status and key technical points of intravascular interventional surgical robotics research, we performed a systematic literature search to retrieve original articles related to remote vascular interventional surgery robotics published up to December 2020. This review, which includes 113 articles published in English, introduces the mechanical and structural characteristics of various aspects of vascular interventional surgical robotics, discusses the current key features of vascular interventional surgical robotics in force sensing, haptic feedback, and control methods, and summarizes current frontiers in autonomous surgery, long-distance robotic telesurgery, and magnetic resonance imaging (MRI)-compatible structures. On the basis of summarizing the current research status of remote vascular interventional surgery robotics, we aim to propose a variety of prospects for future robotic systems.

10.
Theranostics ; 12(4): 1769-1782, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35198072

RESUMO

Background: Though lipiodol formulations are major options in transcatheter arterial chemoembolization (TACE) of advanced unresectable hepatocellular carcinoma (HCC) in the clinic, their application is severely limited by insufficient physical stability between the hydrophobic lipiodol and hydrophilic drugs; thus, most chemotherapeutic drugs are quickly released into systemic circulation resulting in poor therapeutic outcomes and serious side effects. Methods: The typical hydrophilic drug doxorubicin hydrochloride (DOX) was prepared as a pure nanomedicine and then stably and homogeneously dispersed in lipiodol (SHIFT&DOX) via slightly ultrasonic dispersion. The drug release profiles of SHIFT&DOX were defined in a decellularized liver model. In vivo therapeutic studies were performed in rat-bearing N1S1 orthotopic HCC models and rabbit-bearing VX2 orthotopic HCC models. Results: SHIFT&DOX features an ultrahigh homogeneous dispersibility over 21 days, which far surpassed typical Lipiodol-DOX formulations in clinical practice (less than 0.5 h). SHIFT&DOX also has excellent sustained drug release behavior to improve the local drug concentration dependence and increase the time dependence, leading to remarkable embolic and chemotherapeutic efficacy, and eminent safety in all of the orthotopic HCC models. Conclusions: The carrier-free hydrophilic drug nanoparticle technology-based lipiodol formulation provides a promising approach to solve the problem of drug dispersion in TACE with the potential for a translational pipeline.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/métodos , Doxorrubicina/química , Óleo Etiodado/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Coelhos
11.
Eur J Nucl Med Mol Imaging ; 49(8): 2605-2617, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34939176

RESUMO

PURPOSE: To surmount the critical issues of indocyanine green (ICG), and thus achieving a precise surgical navigation of primary liver cancer after long-term transcatheter arterial embolization. METHODS: In this study, a facile and green pure-nanomedicine formulation technology is developed to construct carrier-free indocyanine green nanoparticles (nanoICG), and which subsequently dispersed into lipiodol via a super-stable homogeneous lipiodol formulation technology (SHIFT nanoICG) for transcatheter arterial embolization combined near-infrared fluorescence-guided precise hepatectomy. RESULTS: SHIFT nanoICG integrates excellent anti-photobleaching capacity, great optical imaging property, and specific tumoral deposition to recognize tumor regions, featuring entire-process enduring fluorescent-guided precise hepatectomy, especially in resection of the indiscoverable satellite lesions (0.6 mm × 0.4 mm) in rabbit bearing VX2 orthotopic hepatocellular carcinoma models. CONCLUSION: Such a simple and effective strategy provides a promising avenue to address the clinical issue of clinical hepatectomy and has excellent potential for a translational pipeline.


Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Nanopartículas , Cirurgia Assistida por Computador , Animais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Óleo Etiodado , Humanos , Verde de Indocianina , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imagem Óptica/métodos , Coelhos , Cirurgia Assistida por Computador/métodos
12.
Sci Adv ; 7(51): eabl5862, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34919434

RESUMO

Precise and noninvasive theranostic methods to quantify and deplete focal iron are of crucial importance for iron-overload disorders. Here, we developed an indocyanine green (ICG)­based imaging platform to reveal Fe3+ in vitro and in vivo. The high sensitivity and specificity of ICG-Fe interaction facilitated MR images with a marked correlation between T1 signal intensity ratio (T1SIR) changes and Fe3+ concentration in rodent models and humans. On the basis of these findings, a rational design for coordination-driven self-assembly ICG-Lecithin (ICG/Leci) was proposed to determine Fe3+. The enhancement of photoacoustic signal at 890 nm with increasing Fe3+ concentration showed an over 600% higher linear slope than that of T1SIR changes in animal models. ICG/Leci also promoted a 100% increase in iron depletion in the liver compared with deferoxamine. The high MR sensitivity and superior photoacoustic contrast, combined with enhanced iron depletion, demonstrate that ICG/Leci is a promising theranostic agent for simultaneous detection and treatment of iron-overload disorders.

13.
Front Oncol ; 11: 753286, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692537

RESUMO

Precision interventional brachytherapy is a radiotherapy technique that combines radiation therapy medicine with computer network technology, physics, etc. It can solve the limitations of conventional brachytherapy. Radioactive drugs and their carriers change with each passing day, and major research institutions and enterprises worldwide have conducted extensive research on them. In addition, the capabilities of interventional robotic systems are also rapidly developing to meet clinical needs for the precise delivery of radiopharmaceuticals in interventional radiotherapy. This study reviews the main radiopharmaceuticals, drug carriers, dispensing and fixation technologies, and interventional robotic precision delivery systems used in precision brachytherapy of malignant tumors. We then discuss the current needs in the field and future development prospects in high-precision interventional brachytherapy.

14.
Adv Sci (Weinh) ; 8(16): e2101242, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34166580

RESUMO

Tumor angiogenesis is a complex process that is unamenable to intravital whole-process monitoring, especially on microscopic assessment of tumor microvessel and quantifying microvascular hemodynamics before and after the nanotherapeutics, which hinder the understanding of nanotheranostics outcomes in tumor treatment. Herein, a new photoacoustic (PA) imaging-optical coherence tomography angiography (OCTA)-laser speckle (LS) multimodal imaging strategy is first proposed, which is not only able to precisely macro guide the thermo-chemotherapy of tumor by monitoring blood oxygen saturation (SaO2 ) and hemoglobin content (HbT), but also capable of long-term microscopic investigating the microvessel morphology (microvascular density) and hemodynamics changes (relative blood flow) before and after the nanotherapeutics in vivo. Moreover, to realize the tumor thermo-chemotherapy treatment based on this novel multimodal imaging strategy, a 2D 5-fluorouracil silicon nanosheets (5-Fu-Si NSs) therapeutic agent is designed. Furthermore, 2D high-resolution tumor microvascular images in different stage display that tendency of the thermo-chemotherapy effect is closely associated with tumor angiogenesis. Taken together, the investigations establish the fundamental base in theory and technology for further tailoring the novel specific diagnosis and treatment strategy in tumor. More importantly, this technique will be beneficial to evaluate the tumor microvascular response to nanotherapeutics at microscale.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Glioma/diagnóstico por imagem , Glioma/tratamento farmacológico , Técnicas Fotoacústicas/métodos , Tomografia de Coerência Óptica/métodos , Animais , Modelos Animais de Doenças , Fluoruracila/uso terapêutico , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Imagem Multimodal/métodos , Nanoestruturas/uso terapêutico , Saturação de Oxigênio , Silício/uso terapêutico
15.
Micromachines (Basel) ; 11(9)2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32854264

RESUMO

Transcatheter arterial chemoembolization (TACE) is the common choice of non-open surgery for hepatocellular carcinoma (HCC) now. In this study, a simple TACE robotic system of 4-degree-of-freedom is proposed to get higher accuracy and stability of the surgery operation and reduce X-ray exposure time of the surgeons. The master-slave control strategy is adopted in the robotic system and a customized sigmoid function is designed to optimize the joystick control of the master-slave robotic control system. A force-sensing module is developed to sense the resistance of the guide wire in linear delivery motion and an auxiliary bending feedback method based on constraint pipe with a film sensor is proposed. With two force-sensing methods, the safety strategy of robotic motion with 9 different motion constraint coefficients is given and a human-computer interface is developed. The TACE robot would monitor the value of the force sensor and the analog voltage of the film sensor to adopt the corresponding motion constraint coefficient in every 10 ms. Vascular model experiments were performed to validate the robotic system, and the results showed that the safety strategy could improve the reliability of the operation with immediate speed constraint and avoid potential aggressive delivery.

16.
J Control Release ; 323: 635-643, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32302761

RESUMO

Accurate identification of surgical margins for malignancy remains a challenge in the surgical therapy of cancer, and this encountered interoperative difficulties which directly contribute to the prognosis of patients. In recent years, indocyanine green (ICG) has been approved and applied in clinical settings for lesions detection, especially for the precise surgical resection. However, rapid clearance and poor stability greatly limit its clinical practicality. Herein, a super-stable homogeneous iodinated formulation technology (SHIFT) is designed to realize sufficient dispersion of ICG into lipiodol (SHIFTs) for transcatheter embolization (TAE) synergistic fluorescence-guided resection. Particularly, SHIFTs is prepared in a green physical mixture via a carrier-free manner, which possesses controlled morphology, long-term stability, and improved optical characteristics of ICG (fluorescence/photoacoustic/photothermal activities). Furthermore, the viscosity of the synthetic solvent is comparable to lipiodol, and further assessment demonstrated the same efficacy in computed tomography. The performance of SHIFTs in the fluorescence navigation was further evaluated in vivo by TAE therapy to the rabbit VX2 tumor model for a two-week monitor. The integration of near-infrared fluorescence surgery navigation and TAE could effectively guarantee the precise resection for hepatocellular carcinoma. This SHIFT system provides good potentials for ameliorating the dilemma of precise fluorescent navigation for surgical resection after arterial embolization in clinical practice.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Corantes , Óleo Etiodado , Humanos , Verde de Indocianina , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Coelhos
17.
Biomater Sci ; 8(6): 1575-1579, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32096499

RESUMO

Perihilar cholangiocarcinoma (PHCC) presents a formidable challenge due to its occult anatomic location, aggressive growth, insensitivity to conventional chemotherapy, and poor prognosis. Herein, we engineered a human epidermal growth factor receptor 2 (HER2) affibody to the surface of cell membrane nanovesicles (A-NVs) in a ligand-oriented manner and loaded them with indocyanine green (ICG) as precision theranostics for PHCC treatment. The A-NVs@ICG were prepared and exhibited satisfactory targeting effects in HER2-overexpressing PHCC cells. In vivo fluorescence and photoacoustic imaging demonstrated that A-NVs@ICG promoted the accumulation of ICG in PHCC tissue, leading to enhanced tumor regression and improved anti-cancer effects when combined with photoirradiation. Therefore, bio-engineered A-NVs@ICG represent a promising nanotheranostic agent for PHCC with potential for clinical translation.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Hipertermia Induzida/métodos , Verde de Indocianina/química , Tumor de Klatskin/terapia , Receptor ErbB-2/antagonistas & inibidores , Proteínas Recombinantes de Fusão/administração & dosagem , Animais , Neoplasias dos Ductos Biliares/metabolismo , Linhagem Celular Tumoral , Células HEK293 , Humanos , Tumor de Klatskin/metabolismo , Camundongos , Nanopartículas , Transplante de Neoplasias , Técnicas Fotoacústicas , Medicina de Precisão , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/farmacologia , Nanomedicina Teranóstica , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Cancer ; 10(4): 1060-1069, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30854112

RESUMO

The characterization of high recurrence rate of HCC after TAE provides insights into persistent issues surrounding the role of adjunct therapies administered with TAE. As a regulator of the HER family, Mig-6 is down-regulated in HCC and predicts the prognosis of HCC. In this study, we found up-regulation the expression of Mig-6 enhances autophagy in HCC cells. This function of Mig-6 is related to the activation of the JNK pathway. Next AAV-9 encoding Mitogen inducible gene 6 (Mig-6) was delivered into VX2 liver transplant tumor of rabbits by using hepatic artery catheter. Wild-type AAV is not associated with any human or animal disease and has very low immunogenicity. There are over 100 different AAV serotypes that vary in the amino acid sequence of their capsid protein. We also describe a novel combination therapy coupling AAV-Mig-6 and TAE in a rabbit model resulted in a growth rate decrease in tumor compared with TAE alone. Furthermore, we show that the changes of LC3b and p62, as well as the p-JNK were consistent with changes in vitro experiments. These results suggest that Mig-6 efficiently inhibits tumor progression in vivo. Our findings suggest that Mig-6 induced autophagy inhibition may become a necessary target for adjunct therapy in TAE.

19.
J Vasc Interv Radiol ; 29(10): 1455-1461, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30217747

RESUMO

PURPOSE: To evaluate whether changes in volumetric iodine concentration (VIC) could serve as a suitable predictor of therapeutic response to microwave (MW) ablation in a rabbit intrahepatic VX2 tumor model. MATERIALS AND METHODS: Sixteen intrahepatic VX2 tumors were transplanted in 8 New Zealand White rabbits treated with MW ablation. Contrast-enhanced dual-energy CT scans were obtained at baseline and follow-up. Therapeutic response assessment by modified Response Evaluation Criteria In Solid Tumors (mRECIST), Choi criteria, and VIC changes was performed. An intraclass correlation coefficient (ICC) was used to characterize consistency of assessment results among the criteria used. Technical success was evaluated with explant pathologic findings as a reference. Correlations between technical success and variations in diameter, CT density, and VIC were analyzed. RESULTS: Disease control was observed in 4, 8, and 10 of the 16 tumors per mRECIST, Choi criteria, and VIC changes, respectively. VIC exhibited strong consistency (ICC = 0.807, P < .0001) with Choi criteria. According to explant pathology, technical success was achieved in 10 of the 16 tumors. There was a moderate correlation between VIC changes and technical success (r = 0.532, P = .034), and no correlation was found between technical success and variations in diameter or CT density. CONCLUSIONS: Compared with mRECIST and Choi criteria, dual-energy CT-derived VIC allowed for better prediction of therapeutic response after MW ablation and could provide a potential imaging biomarker of tumor response to MW ablation in patients with hepatocellular carcinoma.


Assuntos
Técnicas de Ablação , Carcinoma Hepatocelular/cirurgia , Meios de Contraste/administração & dosagem , Iohexol/análogos & derivados , Neoplasias Hepáticas Experimentais/cirurgia , Micro-Ondas , Tomografia Computadorizada por Raios X , Animais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Iohexol/administração & dosagem , Neoplasias Hepáticas Experimentais/diagnóstico por imagem , Neoplasias Hepáticas Experimentais/patologia , Masculino , Valor Preditivo dos Testes , Coelhos , Critérios de Avaliação de Resposta em Tumores Sólidos , Carga Tumoral
20.
Biomaterials ; 133: 144-153, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28437625

RESUMO

It is an ambitious target to improve overall Hepatocellular Carcinoma therapeutic effects. Recently, MW ablation has emerged as a powerful thermal ablation technique, affording favorable survival with excellent local tumor control. To achieve better therapeutic effects of MW ablation, MW sensitizers are prepared for enhanced MW ablation to preferentially heat tumor territory. However, it is still not practicable for treatment of the orthotopic transplantation tumor. Herein, biocompatible and degradable methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid) (mPEG-PLGA) microcapsules with hierarchical structure have been designed for microwave-induced tumor therapy. Chemical drug doxorubicin hydrochloride (DOX·HCl), microwave (MW) sensitizers and CT imaging contrast MoS2 nanosheets and MR imaging contrast Fe3O4 nanoparticles are co-incorporated into the microcapsules. In vitro/vivo MR/CT dual-modal imaging results prove the potential application for guiding synergetic therapy and predicting post-therapy tumor progression in the orthotopic transplantation tumor model. After blocking the tumor-feeding arteries, these microcapsules not only exclude the cooling effect by cutting off the blood flow but also enhance MW heating conversion at tumor site. The focused MW heating makes microcapsules mollescent or ruptured and releases DOX·HCl from the microcapsules, achieving the controlled release of drugs for chemical therapy. Compared with MW ablation, 29.4% increase of necrosis diameter of normal liver in rabbit is obtained under MW ablation combined with transcatheter arterial blocking, and the average size of necrosis and inhibition rate of VX-2 liver orthotopic transplantation tumor in rabbit has increased by 129.33% and 73.46%. Moreover, it is proved that the superselectively arterial administration of the as-prepared microcapsules has no recognizable toxicity on the animals. Therefore, this research provides a novel strategy for the construction of MW-induced microcapsules for orthotopic transplantation tumor ablation with the properties of MW sensitizing, superselective arterial blocking, control release and enhanced accumulation of DOX·HCl, and MR/CT dual-modal imaging, which exhibits great potential applications in the field of HCC therapy.


Assuntos
Cápsulas/química , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Micro-Ondas/uso terapêutico , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Lactatos/química , Ácido Láctico/química , Neoplasias Hepáticas/tratamento farmacológico , Poliésteres/química , Polietilenoglicóis/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos
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