磁场对恶性肿瘤生长的抑制作用

宿主和恶性肿瘤之间的相互作用和生物电磁现象有关。磁场影响肿瘤生长的报道较多,由于磁场的生物效应及其机制都很复杂,进一步研究工作是需要的,我们观测到一定参数的脉冲梯度磁场在不同生物层次上抑制鼠恶性肿瘤生长,磁场诱发癌细胞凋亡和阻塞供应肿瘤的新生血管,由于脉冲梯度磁场抑制癌生长,所以它能成为一种辅助治疗癌症的新方法。     

一定参数的磁场在不同生物层次上抑制恶性肿瘤生长

目的 :在不同生物层次上观测一定参数的磁场抑制恶性肿瘤生长。方法 :用脉冲梯度磁场 (峰值磁场 0 .6- 2 .0T ,磁场梯度 1 0 - 1 0 0T·M - 1 ,脉冲宽度 2 0 - 2 0 0ms,重复频率 0 .1 6- 1 .34Hz)治疗白鼠 ,在不同生物层次上 ,例如生物活体、器官、组织、细胞和大分子 ,能抑制鼠恶性肿瘤生长。结果 :上述磁场诱导癌细胞凋亡和阻塞供应肿瘤的新生血管。磁场对运动离子的洛仑兹力 ,使它们束缚在拉莫尔 (Larmor)半径以内 ,会影响正负带电离子对细胞膜和核膜的渗透能力 ,甚至在细胞膜和核膜上形成空洞。结论 :由于这一磁场抑制癌瘤生长 ,所以它能成为一种治疗癌瘤的新方法。     

超低频脉冲磁场抑制癌瘤和提高细胞免疫功能的实验研究

在报道用电子显微镜观测超低频脉冲磁场(峰值磁场0.6～2.0T,磁场梯度10～100T·m^-1,脉冲宽度20～200ms,重复频率0.16～1.34Hz)抑制鼠S-180肉瘤和加强免疫细胞溶癌作用以后,报道了用Faulgen染色法测定肉瘤细胞核的DNA倍性,和用电镜技术和细胞结构的体视学分析磁场对癌细胞形态的影响,观测到磁场影响癌细胞的代谢:磁场使癌细胞的恶性程度降低,抑制其高速和异形生长;磁场抑制癌细胞的分裂和DNA的复制;磁场提高细胞免疫功能,加强淋巴细胞、浆细胞反应.     

超低频脉冲梯度磁场诱导癌细胞凋亡和抑制癌细胞生长实验研究

观测到磁场诱导鼠癌细胞凋亡的形态特征. 凋亡的癌细胞收缩变圆, 与周围细胞脱离; 异染色质浓缩, 沿核膜内侧排列, 凝结成块; 内质网池状水肿并与细胞膜融合; 出现许多被膜包裹的凋亡小体; 凋亡小体被一些淋巴细胞、浆细胞吞噬. 用原位缺口末端标记法(TUNEL)测定癌细胞凋亡, 发现磁场治疗组的凋亡癌细胞的数目明显大于对照组. 在超低频脉冲梯度磁场作用下, 抑制鼠恶性肿瘤生长和提高免疫细胞的溶癌能力, 核DNA倍性减少, 揭示磁场能阻碍DNA复制, 抑制癌细胞分裂与代谢, 降低其恶性程度和抑制其高速与异形生长.     

超低频脉冲磁场诱导癌细胞凋亡机理研究

我们研究超低频脉冲磁场(峰值0.6~2.0T,梯度10~100T.m-1,脉冲宽度20~200ms,重复频率0.16~1.34HZ)作用于鼠S-180肉瘤。在电镜下观察到肉瘤细胞程序性死亡的许多特征。这一磁场引起约1.5mv的跨膜电位变化,导致钙离子Ca2+内流,促使癌细胞凋亡。磁场对运动电荷的洛仑兹力使运动的带电粒子束缚在拉莫尔(Larmor)半径以内,影响正负带电离子对细胞膜和核膜的渗透能力,甚至在膜上形成空洞。     

静磁场对小鼠黑色素瘤细胞B16生长和氧化应激的影响

目的:利用小鼠黑色素瘤细胞B16,研究静磁场对肿瘤细胞生长和氧化应激的影响,探讨氧化应激介导静磁场影响肿瘤细胞生长的机制,为磁场在肿瘤疾病的治疗中的应用提供理论依据。方法:采用MTT法测定磁场对B16细胞活力的影响;利用流式细胞仪测定静磁场暴露对B16细胞周期分布的影响;利用生物化学方法测定磁场暴露对细胞氧化防御系统相关蛋白酶活性的影响。结果:24 h内50 m T-200 m T静磁场暴露可以抑制B16生长,但超过24 h的磁场暴露可以促进B16生长;100 m T和200 m T静磁场暴露对B16的细胞周期分布没有影响;B16暴露于100 m T和200 m T静磁场48 h,GST活性和GSH/GSSG水平表现为先上升后下降,SOD活性和T-AOC水平先下降后上升,CAT活性没有受到影响。结论:50 m T-200 m T静磁场可以抑制小鼠黑色素瘤细胞B16的生长,诱导肿瘤细胞产生氧化应激。     

磁场对肿瘤细胞抑制作用的试验与分析

目的:用磁场进行小鼠荷瘤和人体的离体癌细胞抑制试验。方法:用装备有NdFeB永磁材料的仪器产生非均匀磁场(磁通密度为0.20T,梯度为0.07T/cm)对荷瘤小鼠和人体的离体癌细胞每天照射0.5小时,12天后解剖检查试验结果。结果:磁场对荷瘤小鼠的癌细胞抑止率达61%(P<0.002),胸腺平均比化疗组重8mg(P<0.01),癌组织的纤维包膜是对照组的2～3倍。谷丙转氨酶(SGPT)低于化疗组的平均值(P<0.001),肝、心肌细胞无损伤;白细胞(WBC)高于化疗组的平均值(P<0.02),免疫功能提高;血红蛋白(Hb)低于化疗组的平均值(P<0.05),局部缺氧,癌细胞呈片状坏死,部分癌组织呈孤岛状。磁疗组无明显毒副作用反应。重复性实验结果相近。小鼠和人体离体癌细胞实验显著性检验无显著性意义。结论:磁场在一定的梯度范围是可以有效的抑制小鼠肿瘤的生长。     

稳恒磁场联合抗肿瘤药物协同杀伤肝癌细胞Hepa1-6

化学疗法为肿瘤临床治疗的常规方法,存在毒副作用大、抗药性强等缺陷。为了提高药物的利用效率,减少药物引起的毒副作用,将8.8 m T稳恒磁场分别与顺铂、阿霉素联用,经MTT检测发现磁场与药物联用可对肝癌细胞Hepa1-6生长具有协同抑制的效应,经HE染色发现联合处理组细胞发生明显的形态学改变。流式细胞仪检测显示磁场能增加顺铂对G2/M期细胞的滞留,而磁场与阿霉素共同作用可将细胞阻止于G1期和G2/M期。经彗星电泳检测表明磁场能够增强药物对DNA的损伤,且原子力显微镜观察发现联合处理组细胞膜表面出现较大且较深的孔洞,表面结构破坏严重。实验结果表明,抗肿瘤药物与磁场联用技术可有效抑制肿瘤细胞的生长,减少药物的使用浓度,为将抗肿瘤药物与磁场应用于临床治疗恶性肿瘤提供了一个全新的思路与策略。     

磁场对肿瘤细胞的抑制作用

目的 :用磁场进行小鼠荷瘤和人体的离体癌细胞抑制试验。方法 :用装备有NdFeB永磁材料的仪器产生非均匀磁场 (磁通密度为 0 .2 0T ,梯度为 0 .0 7T/cm)对荷瘤小鼠和人体的离体癌细胞每天作用0 .5小时 ,1 2天后解剖检查试验结果。结果 :磁场对荷瘤小鼠的癌细胞抑止率达 61 % (p <0 .0 0 2 ) ,胸腺平均比化疗组重 8mg(p <0 .0 1 ) ,癌组织的纤维包膜是对照组的 2～ 3倍。谷丙转氨酶 (SGPT)低于化疗组的平均值 (p <0 .0 0 1 ) ,肝、心肌细胞无损伤 ;白细胞 (WBC)高于化疗组的平均值 (p <0 .0 2 ) ,免疫功能提高 ;血红蛋白 (Hb)低于化疗组的平均值 (p <0 .0 5 ) ,局部缺氧 ,癌细胞呈片状坏死 ,部分癌组织呈孤岛状。磁疗组无明显毒副作用反应。重复性实验结果相近。小鼠和人体离体癌细胞实验显著性检验无显著性意义。结论 :磁场在一定的梯度范围是可以有效的抑制小鼠肿瘤的生长。     

脉冲电场和磁场对高血粘和高凝血影响的比较研究

比较研究脉冲电场和脉冲磁场对高血粘和高凝血的影响,探寻降低血液粘度,抑制凝血过快、过强的物理方法.每份血样等分9份,1份作对照,对另外8份分别作不同的脉冲电场或磁场处理.结果显示不同上升沿速率的脉冲电场和磁场对高血粘和高凝血的影响程度不同,上升沿速率为2.5 × 105T s-1的脉冲磁场使全血表观粘度η降低(P＜0.01)、复钙凝血时间tr变长(P＜0.01),血块的最大剪切应力τax变小(P＜0.01).脉冲磁场作用能改善高血粘和高凝血状况.     

C/EBPα基因与肿瘤

C/EBPα基因是抑癌基因,有抑制增殖、促进分化和调节DNA损伤反应等作用。各种机制如对抗性的蛋白质-蛋白质相互作用、基因突变和翻译后修饰等导致C/EBPα转录抑制或活性丧失,可能诱发肿瘤。本文结合国内外研究现状,介绍C/EBPα基因的结构、功能及与肿瘤的诊断、治疗和预后的关系。     

Role of tumor cell glycoproteins immunologically related to glycoproteins Ib and IIb/IIIa in tumor cell-platelet and tumor cell-matrix interactions

A panel of monoclonal and polyclonal antibodies raised against human platelet GpIb or the GpIIb/IIIa complex were used to detect immunologically related molecules on two cell lines derived from human solid tumors. Human cervical carcinoma (MS751) and human colon carcinoma (clone A) expressed molecules immunologically related to platelet GpIb and GpIIb/IIIa complex. These molecules were localized to their plasma membranes by immunofluorescence and immunocytochemistry. The immunologically related GpIb was evenly distributed on the tumor cell membrane with occasional areas of aggregates, whereas the immunologically related GpIIb/IIIa had a pronounced punctate distribution of aggregates in prefixed cells. When MS751 or clone A cells were pretreated with antibodies against platelet GpIb and/or the GpIIb/IIIa complex, their ability to induce platelet aggregation was significantly inhibited. In addition, when tumor cells were pretreated with antibodies against the platelet IIb/IIIa complex, adherence to fibronectin-coated plates was also significantly inhibited. These results suggest a role for these immunologically related tumor cell glycoproteins in tumor cell-host cell (i.e., platelet, endothelial cells) interactions, tumor cell interactions with components of the subendothelial matrix, and subsequent tumor metastasis.     

Anticachectin/tumor necrosis factor-alpha antibodies attenuate development of cachexia in tumor models

C57BL/6 mice bearing either a transplantable methylcholanthrene-induced sarcoma or Lewis lung adenocarcinoma were passively immunized every other day with a rabbit immunoglobulin fraction raised against murine cachectin/tumor necrosis factor-alpha. Mice bearing methylcholanthrene-induced sarcoma developed tumor-associated hypophagia that was attenuated by anticachectin immunoglobulin treatment. In the same tumor-bearing animals, anticachectin treatment also significantly reduced the extent of carcass protein and fat loss, and reduced tumor weight. Mice bearing Lewis lung adenocarcinoma did not develop significant anorexia or carcass lean tissue depletion as tumor growth progressed, but they lost carcass lipid. Treatment of Lewis lung adenocarcinoma bearing mice with anticachectin antibodies diminished the degree of carcass lipid depletion and prevented plasma hypertriglyceridemia. However, in both tumor models, anticachectin treatment did not affect either the development of anemia, hypoalbuminemia or the increase in serum amyloid P concentrations seen with increasing tumor burden. We conclude that an endogenous cachectin response, inhibitable by exogenously administered antibody, contributes to anorexia and to changes in body fat and protein metabolism in these tumor-bearing animals. Neutralizing endogenous cachectin production with antibodies offers the potential to reduce tissue wasting that is frequently associated with neoplastic disease, but it does not appear to affect all of the hematologic and acute phase responses in these murine tumor models.     

Role of tumor necrosis factor in monocyte/macrophage tumor cytotoxicity in vitro

The ability of activated monocytes/macrophages to exert cytotoxic effects in vitro which are preferentially manifest on target cells displaying a transformed phenotype has elicited intense efforts aimed at a molecular characterization of the underlying mechanism. This multistep reaction is typified by an apparently stringent requirement for conjugation between the effector and target to facilitate cytotoxicity, which has therefore long caused bias against the role of soluble effector molecules in mediating target cell damage. However, several laboratories have recently demonstrated a compelling role for at least one such mediator, tumor necrosis factor (TNF), in cell-mediated cytotoxicity exerted against certain target cells; these studies indicated that specific anti-TNF antibodies could block direct monocyte/macrophage-mediated cytotoxicity of TNF-sensitive targets. More recently we have shown that some targets which are completely resistant to soluble or fluid-phase TNF are effectively lysed by a TNF-dependent mechanism upon coculture with activated macrophages under conditions in which conjugation is facilitated. Furthermore, macrophage-mediated cytolysis of both TNF-sensitive and TNF-resistant targets occurs independently of the action of secreted TNF via this mechanism. The purpose of this review is to consider the implications of distinct modes of effector cell delivery of TNF to the target for molecular characterization of the target injury phase of macrophage-mediated tumor cytotoxicity.     

PI3K/Akt信号传导通路与肿瘤

信号转导通路的异常激活是肿瘤细胞的发生、发展重要步骤,PI3K/Akt 信号通路在人类绝大多数恶性肿瘤中被异常激活,其在肿瘤的增殖、存活、细胞运动、抵抗凋亡、血管发生和转移以及对化疗耐药、放疗抗拒中发挥了重要作用.因此,通过对PI3K/Akt 通路的研究进一步了解肿瘤的发生、发展机制,并寻求抗肿瘤药物的新靶点,本文就 PI3K/Akt 信号转导通路的结构特点、与肿瘤发生、发展的关系及其时放化疗的影响作一综述.     

Vaccination with metastasis-related tumor associated antigen TPD52 and CpG/ODN induces protective tumor immunity

Tumor protein D52 (TPD52) is involved in transformation and metastasis and has been shown to be over-expressed in tumor cells compared to normal cells and tissues. Murine TPD52 (mD52) shares 86% protein identity with the human TPD52 orthologue (hD52). To study TPD52 protein as a target for active vaccination recombinant, mD52 was administered as a protein-based vaccine. Naïve mice were immunized with either mD52 protein and CpG/ODN as a molecular adjuvant or CpG/ODN alone. Two weeks following the final immunization, mice were challenged s.c. with syngeneic tumor cells that over-express mD52. Two distinct murine tumor cell lines were used for challenge in this model, mKSA and 3T3.mD52. Half of the mice immunized with mD52 and CpG/ODN rejected or delayed onset of mKSA s.c. tumor cell growth, and 40% of mice challenged with 3T3.mD52 rejected s.c. tumor growth, as well as the formation of spontaneous lethal lung metastases. Mice immunized with mD52 and CpG/ODN generated detectable mD52-specific IgG antibody responses indicating that mD52 protein vaccination induced an adaptive immune response. In addition, mice that rejected tumor challenge generated tumor-specific cytotoxic T lymphocytes’ responses. Importantly, microscopic and gross evaluation of organs from mD52 immunized mice revealed no evidence of autoimmunity as assessed by absence of T cell infiltration and absence of microscopic pathology. Together, these data demonstrate that mD52 vaccination induces an immune response that is capable of rejecting tumors that over-express mD52 without the induction of harmful autoimmunity.     

HGF／SF-Met signaling in tumor progression

Tumor progression is a multi-step process that requires a sequential selection of specific malignant phenotypes. Met activation may induce different phenotypes depending on tumor stage: inducing proliferation and angiogenesis in primary tumors, stimulating motility to form micrometastases, and regaining the proliferation phenotype to form overt metastases. To study how HGF/SF-induced proliferative phenotypes switch to the invasive phenotype is important for understanding the mechanism of tumor progression and will provide an attractive target for cancer intervention and therapy.     

The zebrafish/tumor xenograft angiogenesis assay

Here we describe a method to study tumor angiogenesis in zebrafish (Danio rerio) based on the injection of proangiogenic mammalian tumor cells into the perivitelline space of zebrafish embryos at 48 h post-fertilization. Within 24-48 h, proangiogenic tumor grafts induce a neovascular response originating from the developing subintestinal vessels. This can be observed at macroscopic and microscopic levels after whole-mount alkaline phosphatase staining of wild-type zebrafish embryos, or by fluorescence microscopy in transgenic VEGFR2:G-RCFP embryos in which endothelial cells express the green fluorescent protein under the control of the VEGFR2/KDR promoter. Angiogenesis inhibitors added to the injected cell suspension or to the fish water prevent tumor-induced neovascularization. The assay is rapid and inexpensive, representing a novel tool for investigating tumor angiogenesis and for antiangiogenic drug discovery. Also, gene inactivation by antisense morpholino oligonucleotides injection in zebrafish embryos may allow the identification of genes involved in tumor angiogenesis.