射频热疗技术在脑胶质瘤治疗中的应用进展

近几年,射频(radio frequency,RF)热疗技术以其靶向、微创、效果好,副作用少等特点,在临床治疗中,尤其是恶性肿瘤的治疗方面,取得了巨大的发展。随着研究的逐步深入,射频热疗技术越来越受到人们的重视,其应用范围也逐渐宽泛。脑胶质瘤呈广泛侵袭性生长,尤其是Ⅲ～Ⅳ级胶质瘤,具有高度间变的生长特点,术后复发快,手术加放化疗的平均生存期仅为8～11个月,严重威胁人类健康,是神经外科治疗领域中最难治疗的肿瘤。因而有关恶性脑胶质细胞瘤发生、发展及治疗的研究一直是神经外科领域的热点之一。本文就射频热疗技术的基本原理、脑胶质瘤治疗现状、射频热疗技术在脑胶质瘤治疗方面的应用,最新研究方向及进展做一综述。     

肿瘤热疗机制与方法的研究进展

本文主要从肿瘤热疗的生物学机制,肿瘤热疗的方法以及当前肿瘤热疗中存在的主要问题等方面综述了该领域的国内外研究进展．提出了其发展的主要方向。     

肿瘤热疗中自动控温、恒温

肿瘤热疗技术在临床上得到了较为广泛的应用,但是对于人体深层部位的肿瘤,由于热能难于传至并集中于肿瘤部位,肿瘤热疗效果不理想.在当前肿瘤热疗中存在的另一个问题,即是准确、快速地测出热疗病灶部位的温度,仍然存在很大的困难,因而热剂量难于掌握,直接影响到肿瘤热疗的疗效.由于锰锌铁氧体磁性微粉吸收剂具有强烈吸收电磁波和存在居里温度的特性,采用在肿瘤热疗过程中,将锰锌铁氧体磁性微粉吸收剂输入血管中,可以达到对肿瘤热疗自动控温、恒温和提高疗效的目的.     

磁性纳米粒子在肿瘤热疗中的应用

本文介绍了肿瘤热疗及其存在的问题,并对磁热疗,磁性纳米粒子材料在热疗中的应用进行了综述。     

应用多晶铁纤维提高肿瘤热疗疗效的基础研究

肿瘤热疗已成为一种重要的治癌手段 ,但是对于人体深层部位的肿瘤 ,由于人体内各部脏器组织对电磁波的干扰及人体内各部分物理特性的非均匀性 ,肿瘤热疗的疗效并不显著。本文提出一种提高肿瘤热疗疗效的新方法 ,它能使肿瘤热疗既适用于浅层肿瘤的治疗又适用于深层肿瘤的治疗 ;通过静脉注射将多晶铁纤维注入血管 ,利用稳恒梯度磁场诱导多晶铁纤维定位于肿瘤病灶局部 ,然后在微波照射下 ,多晶铁纤维将有效地吸收微波能量 ,并将其转换成热能对肿瘤组织加热 ,杀灭肿瘤细胞。本文对多晶铁纤维提高肿瘤热疗疗效的应用基础进行了研究 ,并得出重要结论 ;多晶铁纤维通过很强的畴壁运动损耗和宏观涡流损耗将入射的微波能量转换成热能从而对肿瘤加温 ;热疗过程中当微波频率为 1 1GHz时多晶铁纤维吸收转换微波能量的效率最高 ;稳恒梯度磁场可用于诱导多晶铁纤维定位于肿瘤病灶局部等。随着研究的深入 ,多晶铁纤维将使肿瘤热疗发展成更为重要的肿瘤治疗手段。     

应用多晶铁纤维提高肿瘤热疗疗效的基础研究

肿瘤热疗已成为一种重要的治癌手段,但是对于人体深层部位的肿瘤,由于人体内各部脏器组织对电磁波的干扰及人体内各部分物理特性的非均匀性,肿瘤热疗的疗效并不显。本提出一种提高肿瘤热疗疗效的新方法,它能使肿瘤热疗既适用于浅层肿瘤的治疗又适用于深层肿瘤的治疗：通过静脉注射将多晶铁纤维注入血管,利用稳恒梯度磁场诱导多晶铁纤维定位于肿瘤病灶局部,然后在微波照射下,多晶铁纤维将有效地吸收微波能量,并将其转换成热能对肿瘤组织加热,杀灭肿瘤细胞。本对多晶铁纤维提高肿瘤热疗疗效的应用基础进行了研究,并得出重要结论;多晶铁纤维通过很强的畴壁运动损耗和宏观涡流损耗将入射的微波能量转换成热能从而对肿瘤加温;热疗过程中当微波频率为11GHz时多晶铁纤维吸收转换微波能量的效率最高;稳恒梯度磁场可用于诱导多晶铁纤维定位于肿瘤病灶局部等。随着研究的深入,多晶铁纤维将使肿瘤热疗发展成更为重要的肿瘤治疗手段。     

肿瘤热疗的研究进展

肿瘤热疗是近年来研究的热点。肿瘤热疗后宿主机体的免疫功能发生变化,宿主全身抗肿瘤免疫反应被激活。本文从基础研究和临床试验两个方面对热疗后机体免疫功能的改变及其杀伤肿瘤的机理作一综述。     

肿瘤热疗的研究进展

肿瘤热疗是近年来研究的热点.肿瘤热疗后宿主机体的免疫功能发生变化,宿主全身抗肿瘤免疫反应被激活.本文从基础研究和临床试验两个方面对热疗后机体免疫功能的改变及其杀伤肿瘤的机理作一综述.     

纳米铁氧化物磁热疗相关机制研究进展

热疗作为继手术、放疗和化疗后的肿瘤治疗的重要方法之一,自其诞生之初便受到研究人员和产业部门的关注.磁热疗目前已经应用到前列腺癌、脑部肿瘤等临床实验或治疗中,并取得较好的疗效.本文主要介绍基于磁性纳米颗粒的磁热疗产热物理机制与影响因素,以及磁热的亚细胞水平生物学效应.     

基于磁性纳米材料的肿瘤靶向治疗研究进展

磁性纳米材料具有独特的磁学性质，可响应外磁场，产生力、热等效应。如在静磁场下将药物磁靶向递送至肿瘤部位；低频交变磁场下可将纳米药物主动渗透至病灶部位，实现瘤内均一分布；中频交变磁场作用下磁滞损耗产生热和增强的活性氧，用于肿瘤治疗。磁性纳米材料同时具有尺寸依赖的磁学性质以及表面多功能化等特点，可将磁靶向、分子靶向以及磁热疗联合。此外，磁性纳米材料具有磁共振成像性能以及纳米酶催化特性，使其在肿瘤诊疗一体化治疗方面获得了广泛应用。近年来，纳米给药系统不断被优化，基于磁性纳米材料的肿瘤靶向治疗也得到了长足的发展。鉴于此，本文围绕提高靶向肿瘤治疗效果，从磁靶向药物治疗、被动靶向磁热疗和主动分子靶向磁热疗、纳米酶特性以及诊疗一体化应用等几方面出发，综述了基于磁性纳米材料的肿瘤靶向治疗研究进展。     

调制磁性纳米颗粒提高磁热性能的研究

磁性纳米颗粒具有独特的磁学性质,即在外加交变磁场下因产生磁滞释放热量,使其在生物医学领域,特别是肿瘤磁热疗,获得了广泛应用.到目前为止,磁性纳米颗粒介导的磁热疗成为一种治疗癌症的有效手段,已进入临床三期实验.因此,针对磁性纳米颗粒本身,优化设计尺寸、形貌、组分和表面修饰来提高其磁热性能,进而减小临床应用中的颗粒浓度来最小化毒副作用的研究,对肿瘤治疗及生物医药研究具有十分重要的意义.本综述详述如何优化调制磁性纳米颗粒以提高其磁热性能,为高效、低毒的磁性纳米颗粒的设计提供了指导性的研究方向.     

Cancer hyperthermia using magnetic nanoparticles

Magnetic-nanoparticle-mediated intracellular hyperthermia has the potential to achieve localized tumor heating without any side effects. The technique consists of targeting magnetic nanoparticles to tumor tissue followed by application of an external alternating magnetic field that induces heat through Néel relaxation loss of the magnetic nanoparticles. The temperature in tumor tissue is increased to above 43°C, which causes necrosis of cancer cells, but does not damage surrounding normal tissue. Among magnetic nanoparticles available, magnetite has been extensively studied. Recent years have seen remarkable advances in magnetite-nanoparticle-mediated hyperthermia; both functional magnetite nanoparticles and alternating-magnetic-field generators have been developed. In addition to the expected tumor cell death, hyperthermia treatment has also induced unexpected biological responses, such as tumor-specific immune responses as a result of heat-shock protein expression. These results suggest that hyperthermia is able to kill not only local tumors exposed to heat treatment, but also tumors at distant sites, including metastatic cancer cells. Currently, several research centers have begun clinical trials with promising results, suggesting that the time may have come for clinical applications. This review describes recent advances in magnetite nanoparticle-mediated hyperthermia.     

3D in silico study of magnetic fluid hyperthermia of breast tumor using Fe3O4 magnetic nanoparticles

Modeling and simulation of the temperature distribution, the mass concentration, and the heat transfer in the breast tissue are hot issues in magnetic fluid hyperthermia treatment of cancer. The breast tissue can be visualized as a porous matrix with saturated blood. In this paper, 3D in silico study of breast cancer hyperthermia using magnetic nanoparticles (MNPs) is conducted. The 3D FEM models are incorporated to investigate the infusion and backflow of nanofluid in the breast tumor, the diffusion of nanofluid, temperature distribution during the treatment, and prediction of the fraction of tumor necrosis while dealing with the thermal therapy. All the hyperthermia procedures are simulated and analyzed on COMSOL Multiphysics. The sensitivity of frequency and amplitude of the applied magnetic field (AMF) is investigated on the heating effect of the tumor. The mesh dependent solution of Penne's bioheat model is also analyzed. The simulated results demonstrate successful breast cancer treatment using MNPs with minimum side effects. Validation of current simulations results with experimental studies existing in literature advocates the success of our therapy. The increase in the amplitude and frequency of the AMF increases of the temperature in the tumor. The variation of mesh from coarser to finer increased the temperature through small fractions. We have also simulated the magnetic induction problem where the magnetic field is generated by current-carrying coil conductors induce heat in nearby breast tumors due to excitation of MNPs by magnetic flux. This research will aid treatment protocols and real-time clinical breast cancer treatments.     

Analysis of the Distribution of Magnetic Fluid inside Tumors by a Giant Magnetoresistance Probe

Magnetic fluid hyperthermia (MFH) therapy uses the magnetic component of electromagnetic fields in the radiofrequency spectrum to couple energy to magnetic nanoparticles inside tumors. In MFH therapy, magnetic fluid is injected into tumors and an alternating current (AC) magnetic flux is applied to heat the magnetic fluid- filled tumor. If the temperature can be maintained at the therapeutic threshold of 42°C for 30 minutes or more, the tumor cells can be destroyed. Analyzing the distribution of the magnetic fluid injected into tumors prior to the heating step in MFH therapy is an essential criterion for homogenous heating of tumors, since a decision can then be taken on the strength and localization of the applied external AC magnetic flux density needed to destroy the tumor without affecting healthy cells. This paper proposes a methodology for analyzing the distribution of magnetic fluid in a tumor by a specifically designed giant magnetoresistance (GMR) probe prior to MFH heat treatment. Experimental results analyzing the distribution of magnetic fluid suggest that different magnetic fluid weight densities could be estimated inside a single tumor by the GMR probe.     

Antitumor effects of combined therapy of recombinant heat shock protein 70 and hyperthermia using magnetic nanoparticles in an experimental subcutaneous murine melanoma

Heat shock proteins (HSPs) are recognized as significant participants in cancer immunity. We previously reported that HSP70 expression following hyperthermia using magnetic nanoparticles induces antitumor immunity. In the present study, we examine whether the antitumor immunity induced by hyperthermia is enhanced by administration of recombinant HSP70 protein into the tumor in situ. Hyperthermia was conducted using our original magnetite cationic liposomes (MCLs), which have a positive surface charge and generate heat in an alternating magnetic field (AMF) due to hysteresis loss. MCLs and recombinant mouse HSP70 (rmHSP70) were injected into melanoma nodules in C57BL/6 mice, which were subjected to AMF for 30 min. Temperature within the tumor reached 43°C and was maintained by controlling the magnetic field intensity. The combined treatment strongly inhibited tumor growth over a 30-day period and complete regression of tumors was observed in 20% (2/10) of mice. It was also found that systemic antitumor immunity was induced in the cured mice. This study suggests that novel combined therapy using exogenous HSP70 and hyperthermia has great potential in cancer treatment.     

Hysteresis losses and specific absorption rate measurements in magnetic nanoparticles for hyperthermia applications

BackgroundMagnetic hysteresis loops areas and hyperthermia on magnetic nanoparticles have been studied with the aim of providing reliable and reproducible methods of measuring the specific absorption rate (SAR).MethodsThe SAR of Fe₃O₄ nanoparticles with two different mean sizes, and Ni_1 −xZn_xFe₂O₄ ferrites with 0 ≤ x ≤ 0.8 has been measured with three approaches: static hysteresis loops areas, dynamic hysteresis loops areas and hyperthermia of a water solution. For dynamic loops and thermometric measurements, specific experimental setups have been developed, that operate at comparable frequencies (≈ 69 kHz and ≈ 100 kHz respectively) and rf magnetic field peak values (up to 100 mT). The hyperthermia setup has been fully modelled to provide a direct measurement of the SAR of the magnetic nanoparticles by taking into account the heat exchange with the surrounding environment in non-adiabatic conditions and the parasitic heating of the water due to ionic currents.ResultsDynamic hysteresis loops are shown to provide an accurate determination of the SAR except for superparamagnetic samples, where the boundary with a blocked regime could be crossed in dynamic conditions. Static hysteresis loops consistently underestimate the specific absorption rate but can be used to select the most promising samples.ConclusionsA means of reliably measure SAR of magnetic nanoparticles by different approaches for hyperthermia applications is presented and its validity discussed by comparing different methods.General significanceThis work fits within the general subject of metrological traceability in medicine with a specific focus on magnetic hyperthermia. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editor: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader.     

Hyperthermia in cervical cancer – current status

BackgroundThis article reviews the salient features of recent results of clinical studies. It puts a special emphasis on technical aspects, mechanisms of action together with radiotherapy and chemotherapy and points out areas for additional investigation.AimTo present the current state of knowledge on hyperthermia (HT) and to highlight its role in the treatment of cervical cancer.Materials and methodsThe literature on the clinical use of combined hyperthermia for cervical cancer was analyzed. Clinical outcomes together with the technical aspects and the role of HT were also evaluated.ResultsClinically randomized trials have demonstrated benefit including survival with the addition of hyperthermia to radiation or chemotherapy in the treatment of cervical cancer without significant acute or late morbidities. The technological advances have led to an effective and safer treatment delivery, thermal treatment planning, thermal dose monitoring and online adaptive temperature modulation.ConclusionsDue to rapid development over the last decade of hyperthermia systems and new studies at the basic science and clinical level, the perception of hyperthermia as a part of multimodality treatment in cervical cancer has been changed. However, there is still a need for multicentre randomized clinical trials.     

Glass-ceramic-mediated, magnetic-field-induced localized hyperthermia: response of a murine mammary carcinoma

Hyperthermia has been found to be a useful modality for cancer therapy. In this report, a biocompatible, ferrimagnetic glass-ceramic capable of inducing localized hyperthermia by hysteresis heating upon exposure to an alternating magnetic field is presented. When the glass-ceramic was placed in the region of a subcutaneously transplanted, weakly antigenic breast carcinoma and subjected to the magnetic field, sufficient temperature rise was obtained to cause significant (approximately 50%) tumor regrowth delay and a 12% permanent control. The data demonstrate that glass-ceramic-mediated hysteresis heating may be a useful therapeutic approach in the treatment of cancer which offers the advantage of producing a highly localized and predictable tumor volume hyperthermia.     

Magnetic fluid hyperthermia simulations in evaluation of SAR calculation methods

PurposeThe purpose of this study is to employ magnetic fluid hyperthermia simulations in the precise computation of Specific Absorption Rate functions -SAR(T)-, and in the evaluation of the predictive capacity of different SAR calculation methods.MethodsMagnetic fluid hyperthermia experiments were carried out using magnetite-based nanofluids. The respective SAR values were estimated through four different calculation methods including the initial slope method, the Box-Lucas method, the corrected slope method and the incremental analysis method (INCAM). A novel numerical model combining the heat transfer equations and the Navier-Stokes equations was developed to reproduce the experimental heating process. To address variations in heating efficiency with temperature, the expression of the power dissipation as a Gaussian function of temperature was introduced and the Levenberg-Marquardt optimization algorithm was employed to compute the function parameters and determine the function’s effective branch within each measurement’s temperature range. The power dissipation function was then reduced to the respective SAR function.ResultsThe INCAM exhibited the lowest relative errors ranging between 0.62 and 15.03% with respect to the simulations. SAR(T) functions exhibited significant variations, up to 45%, within the MFH-relevant temperature range.ConclusionsThe examined calculation methods are not suitable to accurately quantify the heating efficiency of a magnetic fluid. Numerical models can be exploited to effectively compute SAR(T) and contribute to the development of robust hyperthermia treatment planning applications.     

胃癌的过继性免疫治疗研究进展

胃癌是目前世界上发病率及致死率较高的恶性肿瘤之一,在东亚地区尤其显著。针对胃癌的治疗手段仍是传统的手术联合化疗、放疗为主,尽管靶向药物治疗提供了新的选择,但其对晚期胃癌的疗效仍然有限。胃癌的免疫治疗作为独特的治疗手段,在近十多年发展较为活跃,特别是过继性免疫治疗手段不断有创新。过继性免疫治疗主要依赖回输具有抗肿瘤活性的细胞,目前回输的细胞由具有非特异性抗肿瘤作用向具有特异性抗肿瘤作用演变,特别是嵌合性抗原T细胞治疗的出现,为进展期胃癌患者提供了有一种潜在的选择。本文对胃癌过继性免疫治疗中采用的不同免疫活性细胞的作用机制、临床应用等进行总结,并针对其不足提出利用基因工程技术增强治疗靶向性、降低免疫逃逸的研究方向。