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。     

^H磁共振波谱在脑胶质瘤的应用进展

磁共振波谱（magnetic resonance spectroscopy,MRS）技术的出现使活体检测组织的代谢和生化信息成为可能,随着其技术的不断成熟,其在临床的应用范围日益扩大。脑胶质瘤具有与正常脑组织不同的代谢特征,借助MRS技术一方面可以反映其代谢特征,另外可将其与正常脑组织区分,因此MRS技术特别是^1H-MRS在脑胶质瘤的诊断、鉴别诊断、分级及预后评估中应用日益广泛。本文就相关进展进行综述。     

PTEN在脑胶质瘤中的研究进展

本文叙述了当前国内外抑癌基因 PTEN(phosphatase and tensin homology deleted on chromosome ten,PTEN)在胶质瘤细胞中的信号传导通路的最新进展.文中阐述了 PTEN 的分子结构、胶质瘤中的表达、相关信号传导通路以及在胶质瘤的发生、侵袭、增殖、凋亡等中的作用.研究表明,PTEN 对于胶质瘤的早期诊断和对胶质瘤的基因治疗可能具有重要的意义.     

1H磁共振波谱在脑胶质瘤的应用进展

磁共振波谱(magnetic resonance spectroscopy,MRS)技术的出现使活体检测组织的代谢和生化信息成为可能,随着其技术的不断成熟,其在临床的应用范围日益扩大.脑胶质瘤具有与正常脑组织不同的代谢特征,借助MRS技术一方面可以反映其代谢特征,另外可将其与正常脑组织区分,因此MRS技术特别是1H-MRS在脑胶质瘤的诊断、鉴别诊断、分级及预后评估中应用日益广泛.本文就相关进展进行综述.     

脑胶质瘤动物模型的研究及应用进展

脑胶质瘤约占中枢神经肿瘤的一半,临床治疗效果差。尤其是胶质母细胞瘤,其恶性程度极高,预后性差,是威胁人类健康的主要恶性肿瘤之一,因此,选择一种有效的动物模型是研究脑胶质瘤发病机制及其治疗方法的关键。随着分子生物学、遗传学的发展,尤其是转基因小鼠,以及其他越来越多模式生物的出现,目前已建立了多种脑胶质瘤动物模型。该文将对目前所建立的各种脑胶质瘤动物模型予以综述。     

放疗联合热疗治疗68例晚期卵巢癌术后复发的放疗联合热疗临床观察

目的:探讨放疗联合热疗治疗晚期卵巢癌术后复发的临床疗效。方法:选择哈医科大学第四临床医院及黑龙江省第二肿瘤医院2010年3月~2013年3月收治的68例卵巢癌术后复发患者(均为术后化疗6-8个疗程盆腔复发),将其随机分为热疗联合放疗组(实验组)和单纯化疗组(对照组)。所有患者均给予化疗6-8个周期以上,实验组在放疗结束后2小时内进行热疗,2次/周,共6-8周。通过影像学检查治疗前后肿瘤体积的变化进行疗效评估,观察两组治疗期间各种不良反应的发生情况及术后3年的生存情况。结果:观察组肿瘤完全缓解率(CR)实验组明显高于对照组(P0.05)。皮肤损伤的发生率显著高于对照组,而白细胞计数下降的发生率明显低于对照组(P0.05)。两组随访1、2年的生存率无明显差异(P0.05),实验组第3年的生存率明显高于对照组(P0.05)。结论:热疗联合放疗可提高晚期卵巢癌术后复发的临床疗效。     

脑星形胶质瘤基因表达及其与临床病理的关系

采用原癌基因Ｂｃｌ－２、Ｐ２１及抑癌基因Ｐ５３、Ｒｂ蛋白４种抗体,用ＡＢＣ免疫组织化学方法对４０例脑星形胶质瘤组织作免疫组化染色．结果发现：Ｂｃｌ－２及Ｐ５３基因表达在Ⅰ～Ⅳ级胶质瘤中阳性率有显著性差异,而且染色强度也有明显差异．Ｐ２１、Ｒｂ基因表达在Ⅰ～Ⅳ级胶质瘤中呈上升趋势,但仅在Ⅰ～Ⅲ级、Ⅰ～Ⅳ级之间有明显差异．可以认为：Ｂｃｌ－２、Ｐ５３、Ｐ２１、Ｒｂ在胶质瘤的发生中发挥一定的作用,尤其是Ｂｃｌ－２、Ｐ５３基因,这些基因蛋白的表达与胶质瘤恶性程度有关．测定胶质瘤中的Ｂｃｌ－２、Ｐ５３、Ｐ２１、Ｒｂ蛋白对于胶质瘤的诊断、鉴别诊断以及判断肿瘤的恶性程度与预后均有一定意义．     

复发性卵巢癌患者放疗联合热疗的临床观察

目的:探讨热疗联合放疗在复发性卵巢癌治疗中的协同增敏作用。方法:68例晚期复发性卵巢癌患者,将其随机分为单纯放疗组(对照组)和热疗联合放疗组(实验组)。两组盆腔三维适形放疗单次剂量为200 c Gy,1次/日,5次/周。实验组在放疗结束后2小时内进行热疗,2次/周,共5周。治疗前及治疗结束后1个月均通过超声及CT检查对两组患者肿瘤体积的变化进行疗效评估,同时观察两组患者治疗后3年的生存情况。结果:近期疗效中发现,实验组11例完全缓解,17例部分缓解,对照组3例完全缓解,15例部分缓解,两组总有效率及完全缓解率差异均有统计学意义(P0.05)。实验组3年总的生存率明显高于对照组,差异有统计学意义(P0.05)。结论:热疗联合放疗可有效的杀灭复发的卵巢恶性肿瘤细胞,可缓解放疗副反应,明显提高患者的生存率。     

常规磁共振成像结合磁共振波谱在临床脑胶质瘤诊断及鉴别诊断中的应用价值

目的:分析磁共振氢质子磁共振波谱(Proton Magnetic Resonance Spectroscopy,1H-MRS)的特征与脑胶质瘤病理分级的相关性,探讨氢质子磁共振波谱及常规磁共振成像(Magnetic Resonance Imaging,MRI)联合应用在提高脑胶质瘤的临床诊断中的应用价值.方法:脑胶质瘤(经临床手术证实及病理诊断确诊)患者34例,参照国际卫生组织诊断标准,分为低级别胶质瘤组及高级别胶质瘤组.其中,低级别组16例,高级别组18例,在行常规MRI检查的同时,配合1H-MRS检查,测NAA(N-乙酰天门冬氨酸)、Cho(胆碱)、Cr(肌酸)值,在不同级别胶质瘤、同级别胶质瘤不同位置的代谢物进行综合分析.结果:在获得常规MRI图像并进行诊断后,进行氢质子磁共振波谱检测分析:在低级别胶质瘤及高级别胶质瘤患者中,Cr(肌酸)的总量变化不大,有轻度的下降;而NAA(N-乙酰天门冬氨酸)下降程度较为明显;Cho(胆碱)则明显升高.低级别胶质瘤及高级别胶质瘤患侧的肿瘤组织同对侧的正常脑组织的各种代谢物及其比值(Cho、NAA、NAA/Cho、NAA/Cr值)具有显著性差异(P＜0.05);低级别胶质瘤及高级别胶质瘤的肿瘤组织的代谢物比值NAA/Cr、NAA/Cho值差异具有显著性(P＜0.05).低级别胶质瘤及高级别胶质瘤的Cho/Cr、NAA/Cho、NAA/Cr值与脑胶质瘤的病理分级具有相关性;在各个比值中,NAA/Cr与NAA/Cho值能够较好地反映脑胶质瘤的病理分级,二者的值呈现负相关;Cho/Cr值呈正相关.结论:常规MRI联合1H-MRS在脑胶质瘤的诊断中,能够有效提高准确性,在临床评估脑胶质瘤的分级、确定范围和鉴别诊断都具有重要的指导作用.     

同步放化疗联合深部热疗治疗中晚期宫颈癌的临床疗效观察

目的观察放化疗联合深部热疗治疗中晚期宫颈癌的临床疗效及不良反应。方法选取本院收治的Ⅱb—Ⅲb期宫颈癌患者70例,分为同步放化疗联合深部热疗组（试验组）和同步放化疗组（对照组）,对照组进行根治性放射治疗,放疗第1天开始行化疗,顺铂40mg静脉滴注1d,化疗6个周期,每周重复。试验组：放化疗方法同对照组,于化疗当天行盆腹腔深部热疗（HG-2000体外高频热疗机）,每次热疗60min,每周1次,共4次。于热疗后1h内行放射治疗。结果两组局部肿瘤消退情况、近期疗效、肿瘤局部控制情况、1年期无瘤生存情况比较,差异有统计（P〈0．05）。两组不良反应比较无统计差异。结论同步放化疗联合深部热疗可以提高患者近期疗效,且无严重的并发症,是中晚期宫颈癌治疗中的一种安全有效的模式,值得进一步研究。     

Decreased Cerebrospinal Fluid Glutamine Levels in Patients with Benign Brain Tumors

Abstract: CSF glutamine concentrations were studied in 12 patients with benign brain tumors (meningioma, craniopharyngioma, or osteofibroma), 12 patients with malignant brain tumors (astrocytoma, medulloblastoma, pinealoblastoma, or chondrosarcoma), 9 patients with non-cerebral tumors, and a reference group of 24 patients. The mean ± SD levels in the benign tumor group (424 ± 124 μ M ) were significantly lower (p < 0.0004) than those in the reference group (642 ± 195 μ M ). There was no significant difference between the CSF glutamine concentrations in the malignant cerebral tumor group (643 ± 210 μ M ) or noncerebral tumor group (599 ± 127 μ M ) and those in the reference group. In patients with benign brain tumors there was indication of an inverse linear relationship between the logarithm of CSF glutamine concentration and tumor diameter.     

重组人脑利钠肽的临床应用进展

近年来,随着心力衰竭、肺动脉高压的病理生理及分子机制的深入研究,使上述疾病在临床药物治疗方面有了很大的进步,其中人脑利钠肽(BNP)作为体内唯一天然的肾素-血管紧张素-醛固酮拮抗剂在诊断及治疗心力衰竭等方面均引起了广泛关注,但由于其在心衰状态下降解快且生物活性明显减弱而限制了临床应用。因此,在心力衰竭治疗上补充外源性BNP成为了又一研究热点。重组人脑利钠肽(rhBNP)是一种人工合成的内源性激素,具有扩张血管、排钠利尿、降低心脏前后负荷、抑制肾素-血管紧张素-醛固酮系统和交感神经系统等作用,能够有效的改善充血性心力衰竭患者的血流动力学障碍。新近研究表明,rhBNP在治疗心血管疾病方面疗效显著,本文将就其在临床中的应用予以综述。     

Treatment of Brain Trauma with Liposomal Superoxide Dismutase

Brain trauma was induced in rats by impact of a steel bar on the head with a force such that damage (as measured by neurological scoring) was reversible in fourteen days. Systemic treatment (intraperitoneal injections) with free bovine copper superoxide dismutase or a liposomal form of the enzyme considerably shortened recovery time to less than half Tests included cranial nerves - cornean and aural reflexes. and sensorial motricity functions — gripping reflexes. displacement reactions, recovery and flexion reflexes, equilibrium tests and spontaneous mobility. Normalisation of EEG recordings was also greatly accelerated in the case of treated animals. No changes of brain glutathione peroxidase, glutathione transferase or Mn superoxide dismutase in traumatized animals were observed. However a slight decrease in Cu-SOD occurs. Cerebral lipoperoxidation is increased in the traumatized animals compared with controls. This increase is reduced on treatment of the rats with liposomal SOD (or the free enzyme). Very small amounts of the exogenous SOD pass the brain barrier. the permeability of which is increased in traumatized animals. The enzyme is particularly concentrated in the cortex. Despite apparent total neurological recovery at 15 days for untreated traumatized animals. significant differences in EEG recordings, in percentage cerebral water content and in histological examination of brain tissue of these controls compared with treated animals were observed with a net improvement in the latter case. The results obtained with this model suggest that clinical treatment of coma states and brain traumas with liposomal superoxide dismutase may have certain advantages over orthodox treatments     

Treatment of Brain Trauma with Liposomal Superoxide Dismutase

Brain trauma was induced in rats by impact of a steel bar on the head with a force such that damage (as measured by neurological scoring) was reversible in fourteen days. Systemic treatment (intraperitoneal injections) with free bovine copper superoxide dismutase or a liposomal form of the enzyme considerably shortened recovery time to less than half Tests included cranial nerves - cornean and aural reflexes. and sensorial motricity functions — gripping reflexes. displacement reactions, recovery and flexion reflexes, equilibrium tests and spontaneous mobility. Normalisation of EEG recordings was also greatly accelerated in the case of treated animals. No changes of brain glutathione peroxidase, glutathione transferase or Mn superoxide dismutase in traumatized animals were observed. However a slight decrease in Cu-SOD occurs. Cerebral lipoperoxidation is increased in the traumatized animals compared with controls. This increase is reduced on treatment of the rats with liposomal SOD (or the free enzyme). Very small amounts of the exogenous SOD pass the brain barrier. the permeability of which is increased in traumatized animals. The enzyme is particularly concentrated in the cortex. Despite apparent total neurological recovery at 15 days for untreated traumatized animals. significant differences in EEG recordings, in percentage cerebral water content and in histological examination of brain tissue of these controls compared with treated animals were observed with a net improvement in the latter case. The results obtained with this model suggest that clinical treatment of coma states and brain traumas with liposomal superoxide dismutase may have certain advantages over orthodox treatments     

Malignant Hyperthermia: An Inherited Disorder of Skeletal Muscle Ca2+ Regulation

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle characterized by muscle contracture and life-threatening hypermetabolic crisis following exposure to halogenated anesthetics and depolarizing muscle relaxants during surgery. Susceptibility to MH results from mutations in Ca²⁺ channel proteins that mediate excitation–contraction (EC) coupling, with the ryanodine receptor Ca²⁺ release channel (RyR1) representing the major locus. Here we review recent studies characterizing the effects of MH mutations on the sensitivity of the RyR1 to drugs and endogenous channel effectors including Ca²⁺ and calmodulin. In addition, we present a working model that incorporates these effects of MH mutations on the isolated RyR1 with their effects on the physiologic mechanism that activates Ca²⁺ release during EC coupling in intact muscle.     

心脉隆注射液联合重组人脑钠肽治疗慢性心衰患者的临床观察

目的:探讨心脉隆注射液联合重组人脑钠肽治疗慢性心衰患者的临床效果及对患者心功能、血清N端脑钠肽前体(N-terminal pro b-type natriuretic peptide, NT-proBNP)、胶原、一氧化氮(Nitric oxide, NO)、内皮素-1(endothelin-1, ET-1)水平的影响。方法:选择2015年1月至2017年5月在我院治疗的慢性心衰患者80例,根据随机数字法将其分为对照组和观察组。对照组采用重组人脑钠肽静脉治疗,观察组在此基础上加用心脉隆注射液,治疗14天。观察和比较两组患者治疗前后的心功能指标、血清NT-proBNP、胶原、NO、ET-1水平的变化、临床疗效及不良反应的发生情况。结果:治疗后,观察组总有效率为97.5%,显著高于对照组(82.5%,P0.05)。治疗前,两组左心射血分数(left ventricular ejection fraction, LVEF)、每搏输出量(SV, Stroke volume)、心脏指数(CI, Cardiac index)、心率(HR, heart rate)、血清NT-proBNP、NO、ET-1、胶原水平比较差异均无统计学意义(P0.05);治疗后,两组LVEF、SV、CI、NO均较治疗前明显升高(P0.05),血清NT-proBNP、ET-1、胶原水平均较治疗前明显下降(P0.05),且观察组治疗前后各指标的变化幅度均显著高于对照组(P0.05)。在治疗过程中,对照组出现1例低血压,2例头疼,1例恶心,不良反应发生率为10%;观察组出现1例头痛,不良反应发生率为2.5%,但两组不良反应发生率比较差异无统计学意义(P0.05)。结论:心脉隆注射液联合重组人脑钠肽治疗慢性心衰的临床疗效显著优于重组人脑钠肽静脉治疗,其可有效降低患者血清NT-proBNP、胶原、ET-1的水平并升高血清NO的水平、改善患者心功能,且安全性更高。     

腹腔镜切除与内镜联合治疗胃肠道肿瘤的效果观察

目的：分析腹腔镜联合内镜治疗胃肠道肿瘤的可行性和临床效果。方法：对我院收治的行腹腔镜切除与内镜联合治疗的75例胃肠道肿瘤患者的临床资料进行回顾性分析,其中腹腔镜与胃镜联合治疗34例,腹腔镜与肠镜联合治疗41例。总结分析治疗效果。结果：75例患者中有72例手术成功,3例患者因肿瘤位置不佳中转开腹,腹腔镜与胃镜联合平均手术时间（72.8±12.7）min,出血量5~30mL,术后无吻合口瘘、吻合口出血、腹腔感染等并发症,住院时间（7.5±0.5）d。结论：腹腔镜联合内镜治疗胃肠道肿瘤具有创伤小、手术安全的特点,是一种有效、安全的治疗手段,值得临床推广应用。     

Expression of N-myristoyltransferase in Human Brain Tumors

N-myristoylation is a process of covalent irreversible protein modification that promotes association of proteins with membranes. Based on our previous findings of elevated N-myristoyltransferase (NMT) activity in colonic epithelial neoplasms that appears at an early stage in colonic carcinogenesis, together with elevated NMT expression in human colorectal and gallbladder carcinomas, we investigated NMT activity and protein expression of NMT1 and NMT2 in human brain tumors and documented elevated NMT activity and higher protein expressions. For the first time, we have demonstrated that NMT has the potential to be used as a marker of human brain tumors. However, further studies with larger number of patients are required to establish its role as a complementary diagnostic tool. This finding has significant implications for further understanding of biological mechanisms involved in tumorigenesis, as well as for diagnosis and therapy of human brain tumors.     

The generation of anti-tumoral cells using dentritic cells from the peripheral bloood of patients with malignant brain tumors

 Dendritic cells (DCs) can be the principal initiators of antigen-specific immune responses. We analyzed the in vitro-responses against brain tumor cells using DCs from the peripheral blood of patients with brain tumors. Peripheral blood mononuclear cells (PBMC) were obtained from 19 patients with malignant brain tumors: 12 metastatic brain tumors of lung adenocarcinoma, 7 high-grade astrocytomas. PBMC were cultured with 100 ng/ml of GM-CSF and 10 ng/ml of IL-4 for 5–7 days in order to produce mature DCs. The autologous tumor lysate (5 mg/ml, containing 1 × 10⁶ cells) was then added to the cultured DCs. Using the DCs generated by these treatments, we assessed the changes that occurred in their immune responses against brain tumor via ⁵¹Cr-release and lymphocyte proliferation assays. We found that the matured DCs displayed the typical surface phenotype of CD3⁺, CD45⁺, CD80⁺ and CD86⁺. After the pulsation treatment with tumor lysate, DCs were found to have strong cytotoxic T lymphocyte activity, showing 42.5 ± 12.7% killing of autologous tumor cells. We also found an enhancement of allogeneic T cell proliferation after pulsing the DC with tumor lysate. These data support the efficacy of DC-based immunotherapy for patients with malignant brain tumors. Received: 2 October 2000 / Accepted: 26 April 2001     

CVTP联合化疗方案对初治和复治难治恶性淋巴瘤的临床疗效研究

目的:比较环磷酰胺-西艾克-吡柔比星-泼尼松(Cyclophosphamidum-Vindesine-Tetrahydropyranyl-Prednisone,CVTP)联合化疗方案对初治和复治、难治恶性淋巴瘤的临床疗效。方法:按照化疗史将102例恶性淋巴瘤患者分为初治组59例和复治难治组43例,两组患者均给予CVTP联合化疗方案治疗,比较两组化疗效果、外周血淋巴细胞亚群、毒副反应差别。结果:初治组患者部分缓解(partial remission,PR)率和总有效率(overall response rate,ORR)均显著高于对复治难治组,差异具有统计学意义(P0.05);初治组患者治疗后CD3~+、CD4~+、CD4~+/CD8~++、NK细胞含量均显著高于复治难治组,CD8~+水平显著低于复治难治组,差异具有统计学意义(P0.05);初治组患者化疗期间白细胞下降、血红蛋白下降、血小板减少、恶心呕吐发生率均显著低于复治难治组,差异具有统计学意义(P0.05)。结论:CVTP联合化疗方案治疗初治恶性淋巴瘤近期疗效优于复治难治患者。