铁氧体微粉吸收剂提高肿瘤热疗疗效的机理探讨

铁氧体微粉吸收剂是一种高性能的磁性微波吸收剂。经静脉注射和磁场诱导定位于肿瘤后 ,铁氧体微粉可以充分吸收体外传入的微波能量 ,并将其转换成热能对肿瘤加热 ,因而可以提高热效率、改善热分布的均匀性及消除冷点。本文首先阐述了肿瘤热疗中存在的问题 ,然后介绍了铁氧体微粉在肿瘤热疗中的应用原理和方法 ,分析了铁氧体微粉的发热机理 ,并对铁氧体微粉在肿瘤化疗中的应用进行了探讨。     

铁氧体微粉吸收剂提高肿瘤热疗疗效的机理探讨

铁氧体微粉吸收剂是一种高性能的磁性微波吸收剂。经静脉注射和磁场诱导定位于肿瘤后,铁氧体微粉可以充分吸收体外传入的微波能量,并将其转换成热能对肿瘤加热,因而可以提高热效率、改善热分布的均匀性及消除冷点。本首先阐述了肿瘤热疗中存在的问题,然后介绍了铁氧体微粉在肿瘤热疗中的应用原理和方法,分析了铁氧体微粉的发热机理,并对铁氧体微粉在肿瘤化疗中的应用进行了探讨。     

磁学在乳腺癌诊治中应用进展

近年来生物技术、纳米技术、物理、化学研究等各领域多学科的交叉融合发展,磁学在乳腺癌诊治中应用日趋广泛,本文介绍了核磁共振,免疫磁珠技术,铁氧体微粉吸收剂,磁性药物在乳腺癌诊治中应用进展及其存在问题。     

磁学在乳腺癌诊治中应用进展

近年来生物技术、纳米技术、物理、化学研究等各领域多学科的交叉融合发展,磁学在乳腺癌诊治中应用日趋广泛,本介绍了核磁共振,免疫磁珠技术,铁氧体微粉吸收剂,磁性药物在乳腺癌诊治中应用进展及其存在问题。     

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.     

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。     

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。     

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。     

叶酸修饰的磁性纳米材料在肿瘤诊断和治疗中的应用进展

癌症是威胁人类健康的主要疾病之一,由于检测方法和治疗手段的局限,其成为全球主要的公共卫生难题。叶酸修饰的磁性纳米材料由于同时具有肿瘤细胞靶向性和磁性,不仅可以用于肿瘤组织的成像和肿瘤细胞的检测,还可以用于肿瘤患者的磁热疗、药物载体和基因载体,为肿瘤的靶向诊治提供技术手段。本文综述了叶酸修饰的磁性纳米材料在肿瘤诊断和治疗中的研究进展。     

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.     

肿瘤的超声波治疗

文中就超声波热疗,高强度聚焦超声以及低频超声波在肿瘤治疗中的应用进行了描述。早期主要是利用超声波的热效应来治疗肿瘤,近年来兴起的高强度聚焦超声是热疗法的另一发展。它瞬间使肿瘤组织温度升至65℃以上,导致靶区组织凝固和坏死来达到对肿瘤的“热切除”,是一种安全、有效的肿瘤治疗手段,具有无限潜力。尽管低频超声治疗肿瘤的机制尚不明了,但因其可以诱导细胞凋亡,为肿瘤的治疗提供了新的途径,其治疗作用已受到重视。     

Short-term effects of thermotherapy for spasticity on tibial nerve F-waves in post-stroke patients

Thermotherapy is generally considered appropriate for post-stroke patients with spasticity, yet its acute antispastic effects have not been comprehensively investigated. F-wave parameters have been used to demonstrate changes in motor neuron excitability in spasticity and pharmacological antispastic therapy. The present study aimed to confirm the efficacy of thermotherapy for spasticity by evaluating alterations in F-wave parameters in ten male post-stroke patients with spastic hemiparesis (mean age: 49.0±15.0 years) and ten healthy male controls (mean age: 48.7±4.4 years). The subjects were immersed in water at 41°C for 10 min. Recordings were made over the abductor hallucis muscle, and antidromic stimulation was performed on the tibial nerve at the ankle. Twenty F-waves were recorded before, immediately after, and 30 min following thermotherapy for each subject. F-wave amplitude and F-wave/M-response ratio were determined. Changes in body temperature and surface-skin temperature were monitored simultaneously. The mean and maximum values of both F-wave parameters were higher on the affected side before thermotherapy. In the post-stroke patients, the mean and maximum values of both parameters were significantly reduced after thermotherapy (P<0.01). Hence, the antispastic effects of thermotherapy were indicated by decreased F-wave parameters. Body temperature was significantly increased both immediately after and 30 min after thermotherapy in all subjects. This appeared to play an important role in decreased spasticity. Surface-skin temperature increased immediately after thermotherapy in both groups and returned to baseline 30 min later. These findings demonstrate that thermotherapy is an effective nonpharmacological antispastic treatment that might facilitate stroke rehabilitation.     

Using X-ray in-line phase-contrast imaging for the investigation of nude mouse hepatic tumors

The purpose of this paper is to report the noninvasive imaging of hepatic tumors without contrast agents. Both normal tissues and tumor tissues can be detected, and tumor tissues in different stages can be classified quantitatively. We implanted BEL-7402 human hepatocellular carcinoma cells into the livers of nude mice and then imaged the livers using X-ray in-line phase-contrast imaging (ILPCI). The projection images' texture feature based on gray level co-occurrence matrix (GLCM) and dual-tree complex wavelet transforms (DTCWT) were extracted to discriminate normal tissues and tumor tissues. Different stages of hepatic tumors were classified using support vector machines (SVM). Images of livers from nude mice sacrificed 6 days after inoculation with cancer cells show diffuse distribution of the tumor tissue, but images of livers from nude mice sacrificed 9, 12, or 15 days after inoculation with cancer cells show necrotic lumps in the tumor tissue. The results of the principal component analysis (PCA) of the texture features based on GLCM of normal regions were positive, but those of tumor regions were negative. The results of PCA of the texture features based on DTCWT of normal regions were greater than those of tumor regions. The values of the texture features in low-frequency coefficient images increased monotonically with the growth of the tumors. Different stages of liver tumors can be classified using SVM, and the accuracy is 83.33%. Noninvasive and micron-scale imaging can be achieved by X-ray ILPCI. We can observe hepatic tumors and small vessels from the phase-contrast images. This new imaging approach for hepatic cancer is effective and has potential use in the early detection and classification of hepatic tumors.     

Effect of hyperthermia on tumor blood flow

Differences in blood perfusion rates between tumors and normal tissue can be utilized to selectively heat many solid tumors. Blood flow in normal tissues is considerably increased at temperatures commonly applied during localized hyperthermia. In contrast, tumor blood flow may respond to localized heat typically in two different blood flow patterns: Flow may either decrease continuously with increasing exposure time and/or temperature or flow may exhibit a transient increase followed by a decline. A decrease in blood flow at high thermal doses can be observed in most of the tumors, whereas an increase in flow at low thermal doses seems to occur less frequently. The inhibition of blood flow at high thermal doses may lead to physiological changes in the microenvironment of the cancer cells that increase the cell killing effect of hyperthermia. Flow increases at low thermal doses can enhance the efficiency of other treatment modalities, such as irradiation or the administration of antiproliferate drugs.     

Biomaterial-based technologies for brain anti-cancer therapeutics and imaging

Treating malignant brain tumors represents one of the most formidable challenges in oncology. Contemporary treatment of brain tumors has been hampered by limited drug delivery across the blood–brain barrier (BBB) to the tumor bed. Biomaterials are playing an increasingly important role in developing more effective brain tumor treatments. In particular, polymer (nano)particles can provide prolonged drug delivery directly to the tumor following direct intracerebral injection, by making them physiochemically able to cross the BBB to the tumor, or by functionalizing the material surface with peptides and ligands allowing the drug-loaded material to be systemically administered but still specifically target the tumor endothelium or tumor cells themselves. Biomaterials can also serve as targeted delivery devices for novel therapies including gene therapy, photodynamic therapy, anti-angiogenic and thermotherapy. Nanoparticles also have the potential to play key roles in the diagnosis and imaging of brain tumors by revolutionizing both preoperative and intraoperative brain tumor detection, allowing early detection of pre-cancerous cells, and providing real-time, longitudinal, non-invasive monitoring/imaging of the effects of treatment. Additional efforts are focused on developing biomaterial systems that are uniquely capable of delivering tumor-associated antigens, immunotherapeutic agents or programming immune cells in situ to identify and facilitate immune-mediated tumor cell killing. The continued translation of current research into clinical practice will rely on solving challenges relating to the pharmacology of nanoparticles but it is envisioned that novel biomaterials will ultimately allow clinicians to target tumors and introduce multiple, pharmaceutically relevant entities for simultaneous targeting, imaging, and therapy in a unique and unprecedented manner.     

Survivin的研究现状与RNA干扰在基因治疗中的进展

Survivin是新近发现的凋亡抑制蛋白,在正常组织中不表达而在恶性肿瘤中高表达,与肿瘤的预后、复发、转移关系密切,具有调控细胞周期,凋亡和增殖的作用;还与对化疗的耐药性和放疗的敏感性有关;此外,与肿瘤新生血管的形成关系也十分密切.针对Survivin这些特性,应用新的基因治疗技术-RNA干扰技术降低Survivin的表达可对肿瘤组织的凋亡和增殖产生影响,由于RNA干扰技术具有的高效性,特异性,长效性,使它成为肿瘤基因治疗的重要方法,应用RNA干扰技术针对Survivin靶位降低Survivin的表达有望成为今后肿瘤基因治疗的方向.     

Syngeneic anti-idiotypic antibodies eliminate excess radiolabeled idiotypes at experimental radioimmunolocalization

Significant improvements in tumor/nontumor ratio can be achieved by injections of nonlabeled anti-idiotypic monoclonal antibodies (MAbs) during radioimmunolocalization and radioimmunotherapy using MAbs to target experimental tumors. The in vivo effects of an anti-idiotypic MAb (αH7) against a radioiodinated, high affinity, low dissociation rate, monoclonal antiplacental alkaline phosphatase antibody (H7) was investigated. Following in vivo injection of the anti-idiotypic MAb, the radioactivity in experimental tumors was found to decrease only 25% while the reduction of corresponding radioactivity in nontumor tissues amounted to 65–85%, compared to the group receiving no anti-idiotypic MAbs. These results indicate that it is possible to partially clear the circulation and nontumor tissues from excess of radiolabeled idiotypic antibody, without significant decrease in specific tumor localization, increasing the tumor/ nontumor ratio three- to fourfold. Circulating nontumor targeting radiolabeled antibodies is one of the major limiting factors in radioimmunotherapy today. Injection of anti-idiotypic MAbs could selectively significantly reduce the radiation dose to radiosensitive tissues, i.e., bone marrow and intestine, thus improving efficiency in radioimmunoscintigraphy and radioimmunotherapy.     

Temperature-sensitive loss of tumor characteristics in a tobacco crown gall strain

Summary Three independently isolated tobacco crown gall strains incited byAgrobacterium tumefaciens C58 required phytohormone (auxin and cytokinin) supplements in the basal medium to grow, at 37°C. Six other tobacco crown gall strains incited, respectively, byA. tumefaciens IIBV7, B6, CGIC, A6NC, 27 and AT4 expressed, at 37°C, the tumor characteristic of ability to grow in vitro on medium lacking phytohormones. Nopaline was not detectable in C58 tumors cultured at 37°C, but octopine was produced by B6 tumor tissues incibated at the elevated temperature. C58 tumor strains kept at 37°C for 1 week or more lost the ability to express tumor characteristics at 27°C such as tissue morphology, growth on basal medium lacking phytohormones and nopaline production. Heat-treated C58 tissues also differed from the original tumor strain in regeneration ability and phytohormone requirements of explants; i.e. explants from regenerated, heart-treated C58 tumors required both auxin and cytokinin for growth in vitro.     

A new strategy for cancer therapy based on a predictive indicator.

Tumor-associated genes have been analyzed at the molecular level in recent years, and using the analyses of these genes as a predictive indicator for cancer therapy has attracted attention. Among such genes, the actions of a tumor suppressor gene p53 are focused on the cancer therapy, and it is suggested that p53 genotypes can be used as a predictive indicator for radiotherapy, thermotherapy and chemotherapy. Transfection of wtp53 to p53-null cells increased radiation- or thermo-sensitivity and stimulated apoptosis induced by these therapies. Although therapy-induced apoptosis is suppressed in mp53 cells, apoptosis can be stimulated by glycerol treatment as a chemical chaperone. Therefore, a new strategy of combining p53-targeted gene therapy or chemical chaperone therapies is expected to improve the outcome and efficiency of cancer therapy in the future.     

Average rank-based score to measure deregulation of molecular pathway gene sets

Background

Deregulation of biological pathways has been shown to be involved in the turmorigenesis of a variety of cancers. The co-regulation of pathways in tumor and normal tissues has not been studied in a systematic manner.

Results

In this study we propose a novel statistic named AR-score (average rank based score) to measure pathway activities based on microarray gene expression profiles. We calculate and compare the AR-scores of pathways in microarray datasets containing expression profiles for a wide range of cancer types as well as the corresponding normal tissues. We find that many pathways undergo significant activity changes in tumors with respect to normal tissues. AR-scores for a small subset of pathways are capable of distinguishing tumor from normal tissues or classifying tumor subtypes. In normal tissues many pathways are highly correlated in their activities, whereas their correlations reduce significantly in tumors and cancer cell lines. The co-expression of genes in the same pathways was also significantly perturbed in tumors.

Conclusions

The co-regulation of genes in the same pathways and co-regulation of different pathways are significantly perturbed in tumors versus normal tissues. Our method provides a useful tool for better understanding the mechanistic changes in tumors, which can also be used for exploring other biological problems.