高强度聚焦超声提高机体抗肿瘤免疫的相关机制

高强度聚焦超声(HIFU)是一种治疗肿瘤的新方式,主要通过机械效应、热效应、空化效应等物理方式破坏肿瘤细胞,具有较好的治疗效果。HIFU治疗具有对患者创伤小、对各脏器功能影响小、术后恢复快等优点。近年来许多国内外研究表明HIFU不仅能够减小肿瘤体积,还具有抑制肿瘤转移、提高患者抗肿瘤免疫的效果。本文就HIFU提高肿瘤患者抗肿瘤免疫机制的研究进展做一综述。     

高强度聚焦超声对W256肝癌荷鼠淋巴细胞活性的影响

我们应用高强度聚焦超声 (ＨＩＦＵ )治疗Ｗ 2 5 6肝癌荷鼠 ,并通过四唑蓝(ＭＴＴ)比色法观察荷癌鼠外周血淋巴细胞杀癌细胞活性的变化 ,旨在通过淋巴细胞功能的变化反映高强度聚焦超声对荷癌鼠免疫的影响 ,为其临床应用提供依据。现将结果报道如下。一、材料和方法1.模型的制作 :选用Ｗｉｓｔａｒ大鼠 ,雌雄各半 ,体重 15 0～ 2 5 0 ｇ。质量分数为 3 %戊巴比妥钠 (3 0～ 40ｍｇ/ｋｇ体重 )腹腔注射麻醉。在其肝左叶埋置 1ｍｍ3大小的Ｗ 2 5 6癌块。接种 7～ 10ｄ后可长成直径 0 .5～ 1.0ｃｍ大小的实体癌 ,即可作为Ｗ 2 5 6肝癌荷鼠模型。…     

高强度聚焦超声治疗子宫肌瘤对骶骨影响因素探讨

目的探讨HIFU治疗子宫肌瘤影响骶骨MR的因素。方法子宫肌瘤患者52例,根据子宫位置分为前位、后位、中位三组;依肌瘤位置分为前壁、后壁、侧壁三组;按肌瘤类型分为肌壁间肌瘤、浆膜下肌瘤、黏膜下肌瘤三组;根据肌瘤体积分为〈47 mm3和≥47 mm3两组;按肌瘤距骶骨的距离分为〈30 mm,≥30 mm两组;按HIFU辐照时间分为〈2500 s和≥2500 s两组;根据治疗能量分为〈700 000 J和≥700 000 J两组;按治疗最大功率分为〈340 W和≥340 W两组。采用χ2检验分析骶骨影响的相关因素。结果〈30 mm组较≥30 mm组易导致骶骨出现异常MR信号（P〈0.01）;HIFU辐照时间≥2500 s较易引起骶骨MR异常信号;治疗能量≥700 000 J较易导致骶骨MR异常信号;骶骨MR异常信号与子宫位置、肌瘤位置、肌瘤类型、肌瘤体积及HIFU治疗最大功率无显著相关性（P〉0.05）。结论肌瘤骶骨间的距离、HIFU治疗能量、辐照时间在高强度聚焦超声治疗子宫肌瘤中可能对患者骶骨出现异常MR信号起一定的作用。     

高强度聚焦超声对淋巴管的生物学效应

目的 用高强度聚焦超声(HIFU)辐照大鼠淋巴管,观察产生的生物学变化,探讨HIFU治疗乳糜尿的可行性.方法 将SD大鼠32只随机均分为4组;用高强度聚焦超声辐照大鼠右侧腹股沟区,左侧对照;分别于辐照后24 h、72 h、7 d、30 d观察辐照区及周围组织肉眼及病理改变.结果 HIFU辐照后,大鼠腹股沟淋巴管24 h及72h组表现为管腔变形、破裂等急性损伤改变,7 d及30 d组表现为淋巴管数量减少、管腔闭塞、管周瘢痕形成;各时间组实验侧淋巴管密度(LVD)比自身对照侧明显减少:24 h组为1.100±0.428比1.450±0.411(P＜0.01);72 h组为0.725±0.238比1.575±0.362(P＜0.01);7 d组为0.375±0.198比1.575±0.249(P＜0.01);30 d组为0.175±0.198比1.500±0.400(P＜0.01);辐照后,随时间延长,实验侧LVD明显减少(F=16.669,P＜0.01);辐照后7 d,LVD减少不明显(P＞0.05).结论 高强度聚焦超声可靶向损伤淋巴管,最终使管腔粘连闭塞,因此高强度聚焦超声治疗乳糜尿有可行性.

Abstract：

Objective To investigate the use of high-intensity focused ultrasound ( HIFU) to noninvasively produce biological effect in rat lymphatic vessels in vivo, and the feasibility of HIFU in the treatment of chyluria. Methods Thirty-two SD rats were divided into four groups randomly. The right inguinal regions were irradiated and the left served as controls. At the 1st, 3rd, 7th and 30 day after HIFU irradiation, the gross and pathological changes were observed. Results There were acute changes such as the lymphatic vessels rupture and deformation on the experimental sides at 1st and 3rd day after HIFU irradiation. The number of lymphatic vessels was reduced, lumen was occluded, scar formed around the lumen at 7th and 30th day. The lymphatic vessec density (LVD) on the experimental side was significantly decreased as compared with the controls after HIFU irradiation (experimental sides vs controls: 1st day,1.100 ±0.428 vs 1.450 ±0.411 (P＜0.01); 3rd day, 0. 725 ±0. 238 vs 1.575 ±0.362 (P＜0.01);7th day, 0. 375 ± 0. 198 vs 1. 575 ± 0. 249 ( P ＜ 0. 01); 30th day, 0.175 ± 0.198 vs 1. 500 ± 0.400 (P＜0. 01). There was a significant decrease in LVD on the experimental side with the time going (F = 16.669,P＜0.01). However, there was no significant decrease in LVD at the 7th day (P＞0.05).Conclusion HIFU could precisely damage lymphatic vessels of rats and make lumen occlusion finally,suggesting the feasibility of HIFU for chyluria treatment.     

高强度聚焦超声对21例中晚期原发性肝癌病人免疫状态的影响

目的　探讨高强度聚焦超声 (highintensityfocusedultrasound ,HIFU)对原发性肝癌(hepatocellularcarcinoma,HCC)病人机体免疫状态的影响。 方法　采用重庆海扶技术有限公司研制的HIFU系统 ,治疗中晚期HCC病人 2 1例。分别在治疗前和治疗后 3、7、14、2 1d抽取病人外周静脉血 ,检测细胞免疫和体液免疫的相关指标。HIFU治疗后又行癌灶切除的病例 ,对标本进行光学显微镜、电子显微镜观察。结果　光学显微镜、电子显微镜观察结果显示 ,HIFU治疗区内癌组织发生了不可逆性损伤。CD4治疗前 (34± 13)后 (3、7、14及 2 1d分别为 4 0± 7,37± 7,39± 9,37± 7)差异无显著意义 (F =0 89,P >0 0 5 ) ;其他细胞免疫指标 (CD3 ,CD8,CD4/CD8,CD16)以及体液免疫指标(IgG ,IgA ,IgM ,C3 )治疗前后间的差异亦均无显著意义。结论　HIFU能有效地破坏HCC组织。HIFU治疗中晚期HCC病人难以明显改善机体的免疫状态 ,此时若配合免疫治疗等手段 ,有望使病人获得更好的预后。     

高强度聚焦超声治疗中晚期原发性肝癌对患者免疫状态的影响

目的 观察高强度聚焦超声（HIFU）治疗中晚期原发性肝癌对患者免疫状态的影响。方法 对2003年3月至2003年12月我院收治的40例原发性肝癌患者行HIFU治疗,对其治疗前后进行自身比较并与射频治疗组进行比较,观察分析原发性肝癌患者在接受HIFU治疗后的免疫指标（cD3、cD4、CD8、CD4／CD8、NK、IL-2、TNF）变化。结果 HIFU治疗组与射频治疗组3、6、9个月及1年生存率比较,差异无统计学意义;患者上述各项免疫指标于HIFU治疗前后相比较差异无统计学意义,与射频治疗组比较,差异亦无统计学意义。结论 HIFU治疗中晚期原发性肝癌对患者早期免疫状态的影响不明显。     

高强度聚焦超声体外治疗恶性肿瘤的护理

高强度聚焦超声 (ＨｉｇｈＩｎｔｅｎｓｉｔｙＦｏｃｕｓｅｄＵｌｔｒａｓｏｕｎｄ ,ＨＩＦＵ)治疗肿瘤技术是近几年来发展的新领域 ,该技术利用超声波的组织穿透和可聚焦等物理特性 ,将体外低能量超声波聚焦在体内肿瘤病灶 ,通过焦点区高能量超声波产生的高温、机械效应等 ,使靶区内组织完全毁损[1] 。我科自2 0 0 1年 7月至 2 0 0 2年 4月应用ＨＩＦＵ技术治疗恶性肿瘤病人12 0例 ,取得良好疗效。1　临床资料　　一般资料 :12 0例中 ,男 78例、女 4 2例 ,年龄 976岁 ,平均 4 7 3岁。其中肝癌 78例 ,乳腺癌 2例 ,恶性骨肿瘤 11例 ,软组织肉…     

前列腺癌的高强度聚焦超声治疗

前列腺癌（prostate cancer，PCa）的流行病学显示，前列腺癌发病率正逐年增高。美国的前列腺癌发病率已超过肺癌，据美国抗癌协会估计，2004年美国大约有230110例新发前列腺癌，有29900例将死于此病。在欧洲，每年新发前列腺癌病例大约有260万人，前列腺癌病人占全部男性癌症病人数的11％，占全部男性癌症死亡人数的9％。     

高强度聚焦超声治疗原发性肝癌的疗效

目的探讨高强度聚焦超声（HIFU）对原发性肝癌的治疗效果。方法对我科自2005年5月至2006年8月使用高强度聚焦超声治疗的35例原发性肝癌进行回顾性分析。结果本组术后疼痛症状缓解率为69.6%,术后3月生存率94.29%,6月生存率65.59%,1年生存率57.39%;术后生存期较其自然病程延长。结论高强度聚焦超声治疗原发性肝癌可在一定程度上减轻患者症状、改善患者生存质量、延长患者生存时间。     

高强度聚焦超声治疗的麻醉处理

高强度聚焦超声(high intensity focused ultrasound，HIFU)又称为超声聚焦刀，是近年应用于临床的一种非侵入性肿瘤局部灭活技术。我院自1999年12月至2003年5月，应用HIFU治疗实体瘤315例，取得了良好临床效果。由于HIFU对人体生理有较大影响，因此，该技术的开展给临床麻醉提出了又一新课题，现报告如下。     

维甲酸对体外培养成纤维细胞DNA合成的影响

观察了维甲酸对体外培养成纤维细胞DNA合成的影响,结果证明维甲酸对其合成有不同程度的抑制作用,呈剂量效应关系,并探讨了维甲酸治疗瘢痕的可能作用机理。     

Blood-transfusion-induced suppression of cytotoxic T lymphocyte responses in mice

B6AF1 (H-2KbkDbd) mice were transfused weekly with 0.1 ml of whole blood from DBA/2 (H-2d) mice. One week after each transfusion, spleen and serum samples were collected. Blood transfusions did not induce blood donor alloantigen-specific cytotoxic T lymphocytes (CTL) in spleens of B6AF1 mice. When spleen cells from transfused mice were sensitized to alloantigens in mixed lymphocyte culture in vitro, it was observed that 1-3 transfusions induced suppression of blood donor-specific CTL activity. No suppression of CTL activity was found after 4 transfusions. The cell-mixing experiments demonstrated that the suppression of CTL activity following initial 2 blood transfusions was due to the presence of suppressor cells. The presence of antibodies in sera of transfused B6AF1 mice capable of inhibiting CTL was investigated using the CTL-inhibition test. In these experiments, cytotoxic T lymphoblasts generated in MLC in vitro by culturing normal B6AF1 spleen cells with x-irradiated DBA/2 cells were treated with serum before testing them for cytotoxicity. The antibodies capable of inhibiting CTL responses were demonstrable in sera from transfused mice. Three and four BT sera caused significant inhibition of CTL responses. The CTL-inhibitory antibodies were specific for effector cells of the B6AF1 mice and for target cells of the blood donor DBA/2 mice. These results suggest that the inhibition of CTL responses is caused by antibodies directed against the recognition sites on effector T lymphocytes. The data from this study, therefore, demonstrate that BT cause suppression of the recipient's CTL responses against alloantigens present on the blood donor, and that this suppression is mediated by suppressor cells after the initial 1 to 2 transfusions and by antibodies directed against the CTL antigen-specific receptors after subsequent transfusions.     

Oncologic control provided by HIFU therapy as single treatment in men with clinically localized prostate cancer

Objective

To assess the long term oncologic results of high-intensity focused ultrasound therapy (HIFU) as a primary and single treatment for clinically localized prostate cancer.

Methods

A total of 119 patients with clinically localized prostate cancer underwent HIFU (Ablatherm^®, EDAP, France) as first-line treatment and were retrospectively reviewed. They were stratified according to risk groups proposed by D’Amico. No patient had undergone previous hormonal therapy. PSA level was monitored at 3, 6, 12, 18, 24 months and then yearly. According to the latest ASTRO criteria, failure was defined by a PSA rise of 2 ng/ml or more above the PSA nadir. The biochemical-free survival rate (BFSR) was calculated.

Results

Mean patient age was 68 ± 7.8 years (46–83). Mean follow-up was 3.9 years (1–6.8). Overall 52 patients (43.7%) experienced a biochemical recurrence which included 26, 23 and 3 patients in the low, intermediate and high-risk groups, respectively. In univariate and multivariate analyses, there was a statistical association between preoperative PSA value > 10, a nadir PSA value > 1 and the risk of biochemical recurrence (P < 0.05). The 5-year BFSR rate was 30% with no statistical difference between low- and intermediate-risk patients. None of the 119 patients died of prostate cancer.

Conclusion

High-intensity focused ultrasound therapy provides efficient oncologic control only in patients with low-risk prostate cancer. However, our data could be used to improve the selection of patients who are potential candidates for HIFU therapy.

     

Indications, techniques and outcomes of high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer

High-intensity focused ultrasound (HIFU) is a minimally invasive alternative for patients with localized prostate cancer, not suitable for radical prostatectomy because of a life expectancy less than 10 years or because of major co-morbidities precluding surgery. HIFU can be performed in patients with LUTS (associated TURP) or with a previous history of BPH surgery. HIFU is repeatable after the initial procedure if a recurrent cancer is diagnosed on control biopsies. Furthermore, this therapy is a viable option for patients with a local relapse after external beam radiation therapy: oncologic efficacy is conversely related to the initial prostate cancer stage before radiation therapy.     

Evaluation of color Doppler in guiding prostate biopsy after HIFU ablation

OBJECTIVE: Transrectal ultrasound cannot accurately depict early cancer recurrences after prostate high-intensity focused ultrasound (HIFU) ablation. We evaluated transrectal color Doppler (CD) in guiding post-HIFU prostate biopsy. METHODS: Prostate CD-guided sextant biopsies were obtained in 82 patients who had undergone prostate HIFU ablation for cancer, 24 of whom had hormone therapy before the treatment. At the time of biopsy, a subjective CD score was given to all biopsy sites (0=no flow; 1=minimal flow; 2=suspicious flow pattern). CD findings were compared with biopsy results. RESULTS: CD was a significant predictor of biopsy findings, according to univariate and multivariate site-by-site analysis. However, only 36 of 94 sites with residual cancer had positive CD findings, and thus, negative CD findings should not preclude random biopsy. There was a significant interaction between CD diagnostic capability and a history of hormone therapy before HIFU treatment. CD was a significant and independent predictor of biopsy findings in patients who had not received hormone therapy (odds ratio: 4.4; 95%CI: 2.5-7.9; p<0.0001), but not in those who had (odds ratio: 1.3; 95%CI: 0.5-3.4; p>0.5). CONCLUSION: Biopsy taken in CD-positive sites were 4.4 times more likely to contain cancer in patients who did not receive hormone therapy. CD could not reliably depict cancer recurrence in patients with history of hormone therapy.     

PSA nadir is a significant predictor of treatment failure after high-intensity focussed ultrasound (HIFU) treatment of localised prostate cancer

OBJECTIVES: To assess if prostate-specific antigen (PSA) nadir is an independent predictor of treatment failure and disease-free survival after high-intensity focussed ultrasound (HIFU) therapy for localised prostate cancer as defined by the new ASTRO criteria. METHODS: One hundred three patients after HIFU treatment (Ablatherm, EDAP, Lyon, France) for localised prostate cancer without previous hormonal therapy were evaluated retrospectively. Patients attended regular follow-up visits every 3 mo. Treatment failure was defined by the revised ASTRO criteria (PSA >or=2 ng/ml above nadir PSA, positive biopsy, if salvage treatment was administered). Patients were divided into three PSA nadir subgroups (group 1, 1 ng/ml). The disease-free survival rate (DFSR) was calculated by using life table methods. The log-rank test was used to compare the curves based on Kaplan-Meier models. RESULTS: The median follow-up was 4.9 (3-8.6) yr. Mean time to PSA nadir was 6.4+/-5.1 mo. A PSA nadir of 1ng/ml was reached by 64%, 22.3%, and 13.6% of patients, respectively. Treatment failure rates during follow-up were 4.5%, 30.4%, and 100%, respectively, for the three groups (p<0.001). The actuarial DFSRs at 5 yr were 95%, 55%, and 0%, respectively, for the 3 groups (p<0.001). CONCLUSIONS: The PSA nadir after HIFU correlates highly significantly with treatment failure and DFSR, and can be applied in daily clinical practice. Promising oncological outcome is obtained if a PSA nadir of 相似文献   

Effect of cyclosporine on secondary cytotoxic T lymphocyte responses

Cyclosporine, a potent immunosuppressive agent, inhibits the development of the cytotoxic response in a secondary mixed lymphocyte reaction (MLR) in a dose-dependent manner. Exogenous lymphokines can partially overcome this inhibition. We present evidence that the CsA-resistant cells detected in these responses represent an activated population of memory CTL precursors that require only lymphokines for clonal growth and that kill targets of the original stimulator type only. Recombinant IL-4, when used at high concentrations, can support the generation of CTL in the presence of CsA during a secondary MLR response. The magnitude of the cytotoxic response though is far below the maximal levels achieved either by saturating quantities of rIL-2 or a combination of subsaturable quantities of rIL-2 and rIL-4.     

维甲酸对成纤维细胞作用的体外观察

目的探讨维甲酸治疗瘢痕的作用机理及其用于临床的可能性。方法采用成纤维细胞体外培养技术，并将３ＨＴｄＲ（胸腺嘧啶核苷）掺入成纤维细胞ＤＮＡ中，研究维甲酸对体外培养成纤维细胞生长增殖，ＤＮＡ合成及超微结构的影响。结果维甲酸对成纤维细胞生长增殖，ＤＮＡ合成有不同程度的抑制作用，呈剂量效应关系；扫描电镜和透射电镜观察显示，维甲酸对成纤维细胞合成胶原有抑制作用。结论维甲酸治疗瘢痕的作用机理可能与抑制成纤维细胞生长增殖，阻抑成纤维细胞ＤＮＡ合成及影响成纤维细胞胶原合成有关     

氩氦冷冻联合GM-CSF治疗对荷胶质瘤小鼠脾脏DCs细胞因子分泌及CTLs杀伤活性的影响

【摘要】 目的〓探讨氩氦冷冻联合GM-CSF治疗对荷胶质瘤小鼠脾脏DCs分泌细胞因子及CTLs对肿瘤细胞杀伤活性的影响。方法〓建立C57BL/6小鼠皮下GL261胶质瘤模型,然后随机分为模型对照组、单纯GM-CSF注射组、单纯氩氦冷冻组和联合治疗组。治疗后7天取各组小鼠脾脏制备细胞悬液,部分体外培养,ELISA法检测上清IL-10、IL-12p70、IFN-γ的分泌情况;BD磁珠分选系统分离CD8+ CTLs,与GL261胶质瘤细胞共培养,LDH法检测脾脏CD8+ CTLs杀伤活性。结果〓单纯氩氦冷冻组和联合治疗组小鼠脾脏IL-10分泌水平较模型对照组下降,联合治疗组降低更明显(P均<0.05);单纯氩氦冷冻组和联合治疗组小鼠脾脏IL-12、IFN-γ分泌水平、脾脏CD8+ CTLs杀伤活性均较模型对照组升高,且以联合治疗组升高最为明显(P均<0.05)。结论〓氩氦冷冻联合GM-CSF治疗能通过刺激DCs,分泌大量Th1型细胞因子,从而进一步有效激活T细胞,增强机体特异性抗肿瘤免疫。