过继免疫超声消融后的CTL细胞在荷瘤鼠肿瘤局部的特异性表达

目的探讨过继免疫高强度聚焦超声(HIFU)治疗H_(22)肝癌后活化细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)在荷瘤鼠肿瘤局部的特异性表达。方法 C_(57)鼠在H_(22)肝癌移植后7d分别接受HIFU治疗和HIFU假照治疗。治疗后14 d,密度梯度离心法分离提纯2组荷瘤鼠和正常对照组脾淋巴细胞,乳酸脱氢酶(lactic dehydrogenase,LDH)法测定脾淋巴细胞对H_(22)细胞杀伤活性,同时用MHC肽五聚体荧光染色脾淋巴细胞,计数。C_(57)H_(22)荷瘤鼠随机分为HIFU组、假照组和对照组,分别接受3组染色的淋巴细胞静脉注射。输注1d后处死,取肿瘤组织作冷冻切片,激光共聚焦显微镜观察,图像软件分析。结果 HIFU组淋巴细胞对H_(22)细胞杀伤活性明显增强(P0.05);荧光染色后,在相同数量淋巴细胞中被染的CTL细胞数,HIFU组明显比假照组和对照组多(P0.05);3组红色荧光表达主要分布在肿瘤与正常组织交界区,肿瘤中央区未见表达;HIFU组CTL细胞在肿瘤局部的数量明显多于另两组(P0.05)。结论 HIFU治疗H_(22)移植性肝癌后,活化的CTL细胞能到达同种荷瘤鼠肿瘤局部,发挥特异性抗肿瘤作用。     

高强度聚焦超声治疗H_(22)肝癌后荷瘤鼠淋巴细胞杀伤活性的变化

目的研究高强度聚焦超声(HIFU)治疗H_(22)移植性肝癌后荷瘤鼠淋巴细胞对同种肿瘤细胞的杀伤作用。方法 54只C57BL/6J近交系H_(22)荷瘤鼠随机分为HIFU组,HIFU假照组和对照组。每组有18只荷瘤鼠,分别在H_(22)肝癌移植后7 d接受HIFU治疗,HIFU假照和观察(对照组)。HIFU治疗后14 d,应用乳酸脱氢酶(lactic dehydrogenase,LDH)释放法测定各组鼠在不同效靶比脾淋巴细胞对H_(22)肿瘤细胞体外杀伤活性,ELISA法检测脾淋巴细胞与H_(22)肿瘤细胞共培养24 h后上清液中干扰素-γ(IFN-γ)和肿瘤坏死因子-α(TNF-α)的含量。结果与假照组或对照组比较,HIFU组对H_(22)肿瘤细胞杀伤活性明显增强,且随效靶比增加,差异有统计学意义;HIFU组上清液中IFN-γ和TNF-α的含量明显高于假照组或对照组,差异有统计学意义。结论 HIFU治疗H_(22)移植性肝癌后,荷瘤鼠淋巴细胞对同种肿瘤细胞有较强的杀伤活性,具有特异性抗肿瘤免疫作用。     

亚微米造影剂在高强度聚焦超声消融兔VX2乳腺肿瘤中的应用研究

目的 在高强度聚焦超声(HIFU)消融兔VX2乳腺肿瘤的过程中加入亚微米造影剂,探讨其对辐照效果的影响.方法 制备亚微米造影剂,检测微泡性质.VX2乳腺肿瘤兔随机分组,在不同辐照剂量(150W、120W)和不同辐照时间(5s、3 s)条件下,记录HIFU辐照前后灰阶变化,辐照后行病理检查.结果 成功制备亚微米造影剂.HIFU+亚微米造影剂组较HIFU+ PBS组能够有效提高HIFU的损伤面积,减少辐照强度,缩短辐照时间.结论 亚微米造影剂不仅在诊断方面有特殊的应用价值,在超声治疗领域也有很好的应用前景.     

过继免疫HIFU治疗后活化T淋巴细胞在荷瘤鼠肿瘤局部的功能变化

目的 探讨过继免疫高强度聚焦超声(HIFU)治疗H22移植性肝癌后活化的T淋巴细胞在荷瘤鼠肿瘤局部的功能变化.方法 32只C57BL/6J近交系正常小鼠在H22肝癌移植后7天分别接受HIFU治疗(HIFU组,n=16)和HIFU假照治疗(假照组,n=16).治疗后14天,分离两组荷瘤鼠和正常C57BL/6J鼠(对照组,n=16)的脾淋巴细胞.以乳酸脱氢酶释放法测定各组小鼠脾淋巴细胞对H22细胞体外杀伤活性;另选30只C57BL/6J H22荷瘤鼠随机分为过继免疫HIFU组、过继免疫HIFU假照组和过继免疫对照组,分别静脉注射之前提取的淋巴细胞.输注7天后处死小鼠,手术取出肿瘤组织块,制成单细胞悬液,酶联免疫斑点法检测肿瘤局部T淋巴细胞的功能变化.结果 与假照组和对照组比较,HIFU组对H22细胞杀伤活性明显增强,差异有统计学意义(P均＜0.01);淋巴细胞过继免疫治疗后7天,与过继免疫假照组和过继免疫对照组比较,过继免疫HIFU组能分泌INF-γ淋巴细胞数量明显增加,差异有统计学意义(P均＜0.01).结论 HIFU治疗H22移植性肝癌后,活化的T淋巴细胞在肿瘤局部发挥特异性抗肿瘤效应.     

高强度聚焦超声联合阿霉素治疗兔移植性乳腺癌的疗效评价

目的　探讨高强度聚焦超声 (High intensity focused ultrasound,HIFU)联合阿霉素治疗兔移植性乳腺恶性肿瘤的疗效。方法　 2 1只可移植性鳞癌 (VX2 )兔移植性乳腺肿瘤于肿瘤移植后 3周 ,于腋部扪及直径约 8mm大小的转移淋巴结时随机分为 HIFU 阿霉素治疗组 (7只 ) ,阿霉素治疗组 (7只 ) ,对照组 (7只 ) ,分别接受 HIFU 阿霉素治疗、阿霉素化疗和假照治疗。 HIFU治疗探头频率 1.6 MHz,声强 115 0 0 W/ cm2 ,行全覆盖病灶辐照治疗 ;阿霉素剂量为 2 mg/ kg,分别于 HIFU治疗前3d及治疗后 3周分 2次给药。 HIFU治疗后观察 6个月 ,观察动物的平均存活时间、 6个月存活率及肿瘤的生长和转移情况。结果　 HIFU辐照前肿瘤声像图呈低回声团块 ,辐照后肿瘤声像图呈明显强回声。 HIFU 阿霉素治疗组的平均存活时间、 6个月存活率及肿瘤的转移率分别为 (15 7.2 9± 2 7.2 9) d、4 2 .9%和 0 ,明显优于阿霉素治疗组 [(113.3± 39.3) d、14 .3%和 71.4 % ]和对照组 [(5 9.1± 11.4 ) d、 0和 10 0 % ]。结论　 HIFU联合阿霉素能有效地治疗兔移植性乳腺肿瘤 ,为 HIFU联合化疗药物治疗乳癌的临床研究提供实验依据。     

高强度聚焦超声治疗后荷瘤鼠脾淋巴细胞的免疫治疗作用

目的 探讨高强度聚焦超声(high intensity focused ultrasound,HIFU)治疗H22移植性肝癌后活化的淋巴细胞对早期同种肿瘤的治疗作用及临床意义.方法 32只C57BL/6J近交系H22荷瘤鼠随机分为HIFU组和HIFU假照组,每组16只.分别在H22肝癌移植后7d接受HIFU治疗,HIFU假照和观察(对照组).HIFU治疗后14 d,应用乳酸脱氢酶(lactate dehydrogenase,LDH)释放法测定各组鼠在不同效靶比脾淋巴细胞对H22肿瘤细胞体外杀伤活性;90只C57BL/6J H22荷瘤鼠随机分为HIFU组、HIFU假照组和对照组,分别接受3组提取的淋巴细胞静脉注射.观察各组小鼠肿瘤消退率、肿瘤体积、肿瘤转移发生率及生存率.结果 与假照组和对照组比较,HIFU组对H22细胞杀伤活性明显增强,差异有统计学意义(P＜0.01).接种第60天,与假照组和对照组比较,HIFU组肿瘤消退率明显增加(P＜0.0l);HIFU组肿瘤体积增长缓慢,而假照组与对照组基本相同;与HIFU组比较,假照组和对照组转移率随着病程进展明显增加,差异有统计学意义(P＜0.01);与假照组和对照组比较,HIFU组存活率明显增加(P＜0.01).结论 HIFU治疗H22移植性肝癌后,活化的淋巴细胞对早期同种移植性肿瘤有治疗作用.     

高强度聚焦超声治疗剂量与抑制H22肝癌生长效应的关系

本文研究了一定声强下，高强度聚焦超声（HIFU）不同的照射治疗时间和次数对H22肝癌生长的抑制作用，旨在探讨HIFU治疗肿瘤的最适宜照射时间、次数及照射方式。实验结果表明，HIFU照射治疗剂量、治疗方式、次数及间隔时间的变化对其抑制肿瘤生长的生物学效应均有一定的影响。这一发现对于加强HIFU治疗肿瘤的生物学效应，减少组织的创伤性反应等方面均有一定的临床意义。     

高强度聚焦超声治疗及控制兔肝VX2肿瘤发展的实验研究

目的 探讨高强度聚焦超声(HIFU)治疗及控制肝肿瘤发展转移的效果.方法 采用兔肝VX2肿瘤模型进行HIFU辐照.辐照后不同时期处死动物以观察其病理变化.另以辐照组及对照组动物各8只,于2周后处死,比较肿瘤生长及肺转移的情况.结果 HIFU辐照后肿瘤细胞立即发生凝固性坏死,电镜下亦见到不可逆的破坏.2周后有6只动物的肿瘤原发灶已被完全破坏;另2只靶区外有少量肿瘤残存,其体积为59.8 mm3和10.4mm3,而对照组的肿瘤平均体积为(1571.1±349.7)mm3.辐照组有2只(25%)发生肺转移,转移结节数为10和3;对照组全部发生肺转移,转移结节数为54±30.两组差异有显著性.结论 HIFU对兔肝VX2肿瘤有很强的杀伤作用,对控制肿瘤的发展及转移有一定的疗效.     

介入化疗栓塞协同高能聚焦超声治疗原发性肝癌临床疗效分析

目的:研究介入化疗栓塞(TACE)协同高能聚焦超声(HIFU)治疗失去手术切除的原发性肝癌临床疗效及安全性.方法:应用TACE加HIFU肿瘤治疗机治疗(TACE+HIFU组)原发性肝癌25例患者,单纯行TACE 30例(TACE组)和单纯HIFU治疗的患者25例(HIFU组).观察各组治疗后肿瘤变化、生存时间、甲胎蛋白变化及临床症状改善情况.以x2检验法比较组间差异.结果:TACE+HIFU组治疗后显效7例(28.0%),有效15例(60.0%),无效3例(12.0%);TACE组治疗后显效4例(13.3%),有效8例(26.7%),无效18例(60.0%)(P<0.05);HIFU组治疗后显效2例(8.0%),有效7例(28.0%),无效16例(64.0%)(P<0.05).所有患者无皮肤灼伤、出血/血肿、空腔脏器穿孔及心肺等并发症.结论:TACE协同HIFU治疗原发性肝癌是安全有效的局部治疗方法,且疗效优于单纯TACE治疗及单纯HIFU治疗.     

子宫肌瘤行碘海醇联合HIFU治疗的临床效果观察

资料随机选自2012年5月~2014年5月本院诊治的子宫肌瘤患者74例,随机分为对照组与研究组各37例。对照组予以生理盐水联合HIFU治疗,研究组予以碘海醇联合HIFU治疗,对比两组的HIFU消融能效因子情况,并分析两组患者子宫肌瘤穿刺过程中的反应。结果研究组达到治疗标准的平均消融时间少于对照组,且其消融单位体积肿瘤的所需辐照能量亦少于对照组,两组对比差异较为显著(P<0.05)。碘海醇可促进HIFU能量于肌瘤局部的沉积,从而提高HIFU消融子宫肌瘤的有效率。     

高强度聚焦超声协同紫杉醇热敏脂质体治疗小鼠Lewis肺癌

目的 探讨高强度聚焦超声(HIFU)协同紫杉醇热敏脂质体(PTL)对小鼠Lewis肺癌的治疗效果.方法 建立Lewis肺癌小鼠模型,按肿瘤大小区组随机分为6组,对照组(Con)、单纯HIFU组(HI-FU)、紫杉醇普通注射液组(PTX)、紫杉醇普通注射液联合HIFU组(PTX+HIFU)、紫杉醇热敏脂质体组(PTL)、紫杉醇热敏脂质体联合HIFU组(PTL+HIFU).治疗后,观察肿瘤体积和重量变化,计算抑瘤率,并对肿瘤进行HE染色,观察肿瘤组织病理形态学变化.结果 PTL+HIFU组的抑瘤率为71.6%,显著高于PTX+HIFU组的抑瘤率50.0%(P<0.05),且前两组均高于PTX组(21.3%,P<0.05)和PTL组(23.4%,P<0.05),PTX组和PTL组的抑瘤率未见明显差异(P>0.05).同时,HIFU联合两种不同剂型紫杉醇治疗组较单纯紫杉醇药物治疗组,肿瘤细胞坏死范围和程度均较显著,以HIFU联合紫杉醇热敏脂质体组最明显.单纯紫杉醇药物治疗的两组,肿瘤坏死情况差异不明显.结论 高强度聚焦超声协同紫杉醇热敏脂质体治疗小鼠Lewis肺癌具有明显的抑瘤效果.HIFU可以作为热敏脂质体靶向治疗肿瘤的热源.     

高强度聚焦超声抑制H22肝癌生长的作用

本文探讨了HIFU抑制H22肝癌生长的有效性。实验分为对照组和接受HIFU局部照射治疗的HIFU治疗组。研究结果表明HIFU能明显抑制肝癌的生长和改善肿瘤荷鼠的全身营养状态。讨论了肿瘤局部治疗方式及机理，认为HIFU可能成为未来肿瘤局部治疗具有广阔临床应用前景的一种新方法。     

载10-羟基喜树碱靶向相变纳米粒联合高强度聚焦超声治疗裸鼠肝癌移植瘤

目的探讨叶酸受体靶向的载10-羟基喜树碱(10-HCPT)相变纳米粒(FR-HCPT-PNPCA)造影剂联合高强度聚焦超声(HIFU)对裸鼠肝癌移植瘤的治疗效果。方法采用皮下注射人肝癌7721细胞的方法制备荷瘤裸鼠模型120只,随机分为4组,每组30只,HIFU治疗前1 d分别通过尾静脉注射药物或生理盐水200μl,其中A组注射生理盐水+HIFU辐照,B组注射HCPT+HIFU辐照,C组注射靶向非载药相变纳米粒(FR-PNPCA)+HIFU辐照,D组注射FRHCPT-PNPCA+HIFU辐照。辐照后即刻应用超声观察各组裸鼠肿瘤内灰度变化。2 h后每组处死10只裸鼠,取肿瘤组织行TTC染色观察大体病理并进行组织切片,HE染色后于显微镜下观察肿瘤细胞坏死情况,然后行组织匀浆检查瘤内HCPT浓度。48 h后每组再处死10只裸鼠,取肿瘤组织切片行PCNA和TUNEL染色观察各组肿瘤细胞增殖和凋亡情况。2周后处死各组剩余裸鼠,测量肿瘤大小,并取主要脏器观察肿瘤转移情况。结果辐照后即刻超声显示A、B组辐照区域几乎无灰度变化,C、D组辐照前后灰度变化面积和变化值与A、B组比较,差异均有统计学意义(均P<0.05)。辐照后2h,B、D组瘤内均可检测到HCPT,且D组瘤内HCPT浓度高于B组,差异有统计学意义(P<0.05);A、B组均未见明显凝固性坏死,C、D组肿瘤内均可见明显凝固性坏死,坏死范围与A、B组比较差异均有统计学意义(均P<0.01)。辐照后48 h,D组细胞增殖率最低,细胞凋亡率最高,与A、B、C组比较差异均有统计学意义(均P<0.05)。辐照后2周,D组肿瘤几乎消失,转移灶最少,与A、B、C组比较差异均有统计学意义(均P<0.05)。结论FR-HCPT-PNPCA联合HIFU不仅能实时监控肿瘤HIFU消融并增强消融效果,且释放的药物能辅助治疗肿瘤,有望为肿瘤治疗提供一种精准、高效的方法。     

Pulsed High-Intensity Focused Ultrasound Enhances Apoptosis of Pancreatic Cancer Xenograft with Gemcitabine

We sought to investigate whether concurrent exposure to pulsed high-intensity focused ultrasound (HIFU) and the chemotherapeutic drug gemcitabine would enhance apoptosis in pancreatic cancer. A pancreatic cancer xenograft model was established using BALB/c nude mice and human pancreatic cancer cells (PANC-1). In the first study, mice were randomly allocated into one of four groups: control (n = 4), HIFU alone (n = 4), gemcitabine (GEM) alone (n = 28) and concurrent treatment with HIFU and gemcitabine (HIGEM) (n = 28). The GEM and HIGEM groups were subdivided into four subgroups (16 mice) according to the drug dose injected (50–200 mg/kg) and another four subgroups (16 mice) according to the time interval between drug injection and HIFU treatment (each subgroup, n = 4). Apoptosis rates were evaluated using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay and percentage of necrosis, as evaluated with Harris' hematoxylin solution and eosin Y stain, 3 d after treatment. The second study was performed to evaluate tumor growth rates of the four groups. Each group was treated weekly for 3 wk, and tumor size was periodically measured for up to 4 wk from the beginning of treatment. In the first study, overall rates of apoptosis were significantly higher in the HIGEM group than in the GEM group (p = 0.02). In a subgroup analysis, HIGEM was superior to GEM in enhancing apoptosis at gemcitabine dosages of 150–200 mg/kg gemcitabine and intervals between gemcitabine and HIFU less than 2 h (p = 0.01). In the second study, HIGEM treatment resulted in the slowest tumor growth. However, despite a visible distinction, none of the differences found between the HIGEM and GEM groups were statistically significant (p > 0.05). Treatment with both HIFU and gemcitabine might enhance cell apoptosis and reduce tumor growth in pancreatic carcinoma. For this concurrent treatment, a high dosage of gemcitabine and a short-term delay before HIFU are recommended to maximize the therapeutic effect.     

Pulsed High-Intensity Focused Ultrasound Therapy Enhances Targeted Delivery of Cetuximab to Colon Cancer Xenograft Model in Mice

Our aim was to evaluate whether pulsed high-intensity focused ultrasound (HIFU) therapy enhances the effect of an epidermal growth factor receptor–targeted chemotherapeutic drug, cetuximab, in treating human colon cancer xenografts in a mouse model. Balb/c nude mice with subcutaneous xenografts of HT-29 cells were randomly categorized into control (n = 9), pulsed HIFU alone (n = 10), cetuximab monotherapy (n = 8) or combined pulsed HIFU and cetuximab therapy (n = 9) group. Cetuximab, pulsed HIFU therapy, or both were administered three times per week starting from day 8 after tumor cell injection. Based on tumor growth curves up to 34 days, the combination therapy group showed more suppressed tumor growth than all other groups (p < 0.05). The final relative tumor volumes were 5.4 ± 2.1, 5.2 ± 1.3, 4.8 ± 1.8, and 3.1 ± 0.9 for control, pulsed HIFU alone, cetuximab monotherapy, and combination therapy groups, respectively. In conclusion, pulsed HIFU therapy appears to enhance the anti-tumor effect of epidermal growth factor receptor–targeted cetuximab on human colon cancer xenograft models in mice.     

磁场联合阿霉素磁液靶向治疗鼠种植性胃肿瘤的实验研究

目的　探讨阿霉素磁液经消化道给药后，联合外磁场对鼠种植性胃肿瘤的靶向治疗作用机制。方法　利用Walker-256瘤细胞制作鼠种植性胃肿瘤模型，并分成阿霉素磁液联合外磁场的靶向组，单纯阿霉素治疗的非靶向组及空白对照组。观察动物的一般状况，肿瘤生长率，病理组织学改变及动物生存时间等变化。结果　与空白对照组比较，靶向组动物肿瘤生长明显缓慢，瘤重及瘤体积抑制率分别为78.08%和82.52%(χ     

电化学治疗小鼠S-180肉瘤的最佳电磁脉冲参数比较

背景:电化学治疗是治疗肿瘤的一种新的而有效的工具。这种技术非常容易控制和操作,而且对正常组织副作用小。特别对治疗浅表肿瘤非常有效。在电化学治疗治疗过程中,电磁脉冲参数的选取与构成是非常关键的。目的:利用电化学治疗植入S-180肉瘤的昆明鼠,获得电磁脉冲治疗的最佳参数。单位:四川大学电子信息学院无线电物理教研室。设计:随机分组设计、对照实验。材料:实验于2003-01/2004-05在四川大学生命科学学院细胞实验室完成。选择昆明鼠106只随机分为12组,电压500V、脉冲数为5、电容分别为6,10,14μF组各9只,电压700V、脉冲数为5、电容分别为6,10,14μF组各9只,电压900V、脉冲数为5、电容分别为6,10,14μF组各9只,电压700V、电容10μF、脉冲数分别为7,9组各8只,对照组9只。方法:博来霉素多点腹腔注射入肿瘤块(0.04mg/只),用针状辐射器加上电磁脉冲,每隔2d治疗1次,共3次,18d以后处死小鼠。照射前和照射后第10,18天,测量肿瘤体积,公式为肿瘤体积(mm3)=3.14159×长×宽×高/6。抑制率(%)=(对照组平均肿瘤体积-照射后平均肿瘤体积)/对照组平均肿瘤体积×100%。相对生长速率=照射后肿瘤体积/照射前肿瘤体积。主要观察指标:肿瘤体积;抑制率;相对生长速率。结果:纳入动物106只,均进入结果分析。①当电容是6μF,脉冲数是5而电压变化时犤以第10天为例,电压为500,700,900V时肿瘤体积分别为(66.99±91.17),(62.58±71.83),(78.43±73.91)mm3犦,电压700V时总体效果最好,而电压900V时总体效果较差。②当电压和脉冲数固定而电容变化时(以电压700V,脉冲数为5为例,电容为6,10,14μF时肿瘤抑制率分别为92.14%,90.90%,84.97%),电容6μF时效果最好,电容14μF时效果最差。③当电压和电容固定,而脉冲数在变化时犤以电压700V,电容10μF,第10天为例,脉冲数为5,7,9时肿瘤体积分别为(80.66±38.17),(41.33±36.40),(39.86±23.03)mm3犦,随着脉冲数的增加抑制效果变好,而脉冲数为9时最好。结论:通过实验获得电磁脉冲的最佳参数:当脉冲数是5,电压700V,电容6μF时,抑制肿瘤的效果是最好的;当电压固定在700V,电容固定在10μF时,抑制肿瘤的效果随着脉冲数的增长而增长,并且最好的脉冲数是9。     

High-intensity focused ultrasound tumor ablation activates autologous tumor-specific cytotoxic T lymphocytes

Previous studies have shown that high-intensity focused ultrasound (HIFU) ablation can enhance host antitumor immune response, though the mechanism is still unknown. In the present study, we investigated whether HIFU ablation could activate tumor-specific T lymphocytes and then induce antitumor cellular immunity. We studied 70 C57BL/6J mice bearing the H₂₂ tumor; they were randomly divided into a HIFU group and a sham-HIFU group. Of the mice, 35 in the HIFU group underwent HIFU ablation of the H₂₂ hepatic tumor, and the remaining 35 received a sham-HIFU procedure. In addition, 35 female, naïve syngeneic C57BL/6J mice were used as controls. All mice were sacrificed 14 days after HIFU, and the spleens were harvested. The function of T lymphocytes was determined. As a valuable tool for detecting and characterizing peptide-specific cells, the frequency of MHC class I tetramer/CD8-positive cells was quantified, which could help to determine the response and number of T lymphocytes. The therapeutic effect of the HIFU-activated lymphocytes on tumor-bearing mice was investigated after adoptive transfer of the lymphocytes. The results showed that compared to sham-HIFU and control groups, HIFU ablation significantly increased the cytotoxicity of cytotoxic T lymphocytes (p < 0.05), with a significant increase of IFN-γ and TNF-α secretion (p < 0.001). The frequency of the MHC class I tetramer/CD8-positive cells was significantly higher in the HIFU group (p < 0.05). A stronger inhibition of tumor progression and higher survival rates were observed to be significant after adoptive immunotherapy in the HIFU group as compared to the sham-HIFU and control groups (p < 0.01). It is concluded that HIFU ablation could activate tumor-specific T lymphocytes, thus inducing antitumor cellular immune responses in tumor-bearing mice.     

High-Intensity Focused Ultrasound-Induced,Localized Mild Hyperthermia to Enhance Anti-cancer Efficacy of Systemic Doxorubicin: An Experimental Study

The aim of this study was to evaluate the enhancement of the efficacy of systemic doxorubicin by pulsed high-intensity focused ultrasound (HIFU)-induced, localized mild hyperthermia. For the in vitro study, the intranuclear uptake of doxorubicin by squamous cell carcinoma (SCC)-7 cells incubated at different temperatures was compared. For the in vivo study, mice with SCC-7 tumors were assigned to either the control, conventional hyperthermia, HIFU hyperthermia, doxorubicin-alone, conventional hyperthermia + doxorubicin or HIFU hyperthermia + doxorubicin group. Conventional hyperthermia was induced by immersing the tumor in warm water (42.5°C), and HIFU hyperthermia was induced by HIFU after optimizing the parameters with direct temperature measurements (frequency = 1 MHz, pulse repetition frequency = 5 Hz, power = 12 W, duty cycle = 50%). In the in vitro study, fluorescence was more intense at 42°C than at 37°C and was time dependent. In the in vivo study, tumor growth in the HIFU hyperthermia + doxorubicin group was most prominently suppressed with the highest apoptotic index compared with all other groups (p < 0.05). Pulsed HIFU-induced localized mild hyperthermia enhanced the anti-cancer efficacy of systemic doxorubicin more than conventional mild hyperthermia.