雷公藤内酯醇联合热疗对 MKN28 细胞增殖抑制作用的研究简

目的：研究雷公藤内酯醇（triptolid,TPL）与热疗联合应用对胃癌细胞MKN28增殖、细胞周期分布及磷酸化蛋白激酶B（phosphorylation of Akt,p-Akt）表达的影响。方法：将体外复苏和培养的胃癌细胞系MKN28分为四个组：对照组、TPL组、热疗组、TPL联合热疗组。其中TPL刺激浓度为20ng/ml,热疗采用43℃下加热150min。使用四甲基偶氮唑盐比色法（measurement of trititaed thymidine incorporation,MTT）检测细胞增殖并计算细胞增殖抑制率。流式细胞仪（flow cytometer,FCM）检测细胞周期分布的变化,使用蛋白质印迹法（Western blot）检测p-Akt水平。结果：热疗组,TPL组和TPL联合热疗组MKN28 细胞增殖抑制率分别为21.2%,28.5%和54.5%,联合组显著高于TPL组和热疗组。FCM结果显示热疗组G0/G1期减少至（62.7±3.8）%,G2/M期增多至（18.1±3.2）%。TPL组G0/G1期增多至（80.62±4.6）%,G2/M期增多至（16.18±2.2）%。联合组G0/G1期（77.72±8.1）%,G2/M期增多至（19.62±2.4）%。热疗组和TPL组对细胞周期的影响不一样。与热疗组和TPL组相比,联合组G2/M期增多最明显。Western blot检测各组p-Akt蛋白表达均有降低,其中对照组（1.81±0.05）,热疗组（1.28±0.01）,TPL组（0.95±0.07）,联合组（0.58±0.06）,联合组下降最明显（P＜0.05）。结论：TPL联合热疗对MKN28细胞增殖抑制作用更强,可能与二者对细胞周期的作用点不同,并能同时降低细胞内p-Akt的表达有关。     

Morphologic and morphometric studies on tumor necrosis produced by radiotherapy, and hyperthermia singly and in combination

The purpose of the present study was to evaluate the therapeutic effects of hyperthermia associated with radiotherapy on neoplasia. Two transplanted experimental tumors (undifferentiated carcinoma of mouse breast and sarcoma 37) were used. A protocol was followed that included, for both models, four groups of animals: 1) control group; 2) radiotherapy group; 3) hyperthermia group; 4) radiotherapy associated with hyperthermia group. The animals were sacrificed after therapy according to a different schedule for each type of tumor. The morphology of the neoplasia in every group of treated tumors was compared with that of the control group. For quantitative evaluation of the necrosis, we studied the ratio of the tumor necrotic areas (N) to a tumor standard area (T). From the results obtained, the following conclusions were made: 1) Necrosis produced by combined treatment was significantly greater than that obtained by using one only; 2) necrosis appeared early after treatment and remained relatively unchanged; 3) The damaging effect of the hyperthermia occurred earlier than that produced by radiotherapy when these methods were used separately, thus suggesting distinct mechanisms of tumor necrosis.     

腹腔循环热灌注化疗对恶性肿瘤合并腹水的疗效及安全性—开放、非随机、历史对照研究

目的:评估化疗联合腹腔循环热灌注治疗恶性肿瘤合并腹水疗效及安全性。方法:采用历史对照方法,试验组(100例)采用化疗联合腹腔循环热灌注治疗,对照组(100例)采用化疗联合传统腹水治疗方法,观察两组患者近期疗效、生存情况及不良反应发生。结果:腹腔循环热灌注联合化疗者与传统腹水治疗联合化疗者,治疗腹水的有效率分别为61.0％和47.0％(P=0.047)。两组病人以病种为亚组进行生存分析,经log-rank检验结果并未显示出试验组在2年累积生存率上优于对照组,P值分别是胃癌0.315、卵巢癌0.285、大肠癌0.758、肝癌0.471,两组患者常见不良反应发生率未见统计学差异。结论:化疗联合腹腔循环热灌注治疗晚期恶性肿瘤合并腹水患者安全并且有良好近期疗效,但目前未显示出对患者2年累积生存率有积极作用。     

热疗联合紫杉醇对卵巢癌A2780细胞增殖、侵袭及AKT磷酸化的影响

目的:探讨热疗联合紫杉醇（Paclitaxel）对卵巢癌A2780细胞增殖、侵袭及AKT磷酸化的影响。方法:将A2780细胞分为4组:热疗组(41℃加热90min)、紫杉醇组、热疗联合紫杉醇组及对照组(常规培养细胞)。用MTT法检测细胞增殖情况,测定紫杉醇联合热疗对A2780细胞体外增殖抑制的影响;Transwell侵袭实验检测细胞的侵袭能力的变化,测定紫杉醇联合热疗对A2780细胞体外侵袭能力的影响;Western blot检测各组细胞中AKT磷酸化的变化。结果:热疗联合紫杉醇组细胞增殖率与其他各组比较均明显降低,差异有统计学意义（P＜0.05）;热疗联合紫杉醇组细胞的侵袭能力同样明显减弱,差异有统计学意义（P＜0.05）;同时,热疗联合紫杉醇组细胞中AKT磷酸化水平与其他各组相比亦显著降低,差异有统计学意义（P＜0.05）。结论:热疗联合紫杉醇可通过降低A2780细胞中AKT的磷酸化水平从而明显抑制细胞的增殖及侵袭能力。     

全身热疗联合化疗治疗晚期胃癌的疗效分析

目的：观察全身热疗联合DCF方案化疗治疗晚期胃癌的近期疗效及毒副反应。方法67例晚期胃癌患者随机分为治疗组（32例）和对照组（35例）,2组患者均采用DCF方案全身化疗,化疗第1天在全麻状态下用ET-SPACE全身热疗系统进行全身加热时开始静脉给药。结果治疗组总有效率和生活质量提高率均高于对照组（P均〈0.05）;2组毒副反应发生率比较差异无统计学意义（P均〉0.05）。结论全身热疗联合DCF方案化疗治疗晚期胃癌可以获得较好的近期疗效,改善患者的生活质量,且毒副反应未增加,值得临床进一步推广。     

深部高频热疗联合GO方案治疗胰腺癌的临床观察

目的 探讨深部高频热疗联合GO方案治疗胰腺癌的疗效与安全性.方法 选择收治的胰腺癌患者100例.按照随机数字法分为观察组和对照组各50例.对照组患者给予GO方案化疗,观察组在对照组基础上给予胰腺区域局部深部高频热疗,首次开始于化疗用药后4h内,频率13.56MHz,温度范围41℃～43℃,连续治疗60 min,每周2次,10次1个疗程.结果 观察组患者的ORR为76.0％,DCR为86.0％,对照组患者ORR为36.0％,DCR为66.0％,观察组患者ORR和DCR均高于对照组,差异有统计学意义(P＜0.05).观察组患者疼痛症状改善有效率和体能改善有效率高于对照组,差异有统计学意义(P＜0.05).观察组4例出现Ⅰ～Ⅱ皮肤烫伤,余不良反应与对照组比较无统计学意义(P＞0.05).结论 深部高频热疗联合GO方案化疗临床疗效显著,能明显提高胰腺癌患者生活质量,且安全性较高,值得临床推广使用.     

射频热疗联合胸腔灌注药物治疗乳腺癌致恶性胸腔积液的临床观察

目的： 观察射频热疗联合胸腔灌注华蟾素、顺铂对乳腺癌所致恶性胸腔积液患者的临床疗效和不良反应。方法：62例确诊为乳腺癌伴恶性胸腔积液患者随机分为两组,热疗组32例患者采用射频热疗联合华蟾素与顺铂胸腔灌注治疗,对照组30例患者仅采取华蟾素与顺铂胸腔灌注治疗,治疗进行一月后对两组患者进行近期疗效率及Kamofsky（KPS）评分对比研究。结果：热疗组近期疗效总有效率为87.5％,优于对照组的66.7％;热疗组KPS提高率(93.8%)明显高于对照组(70.0%),差异均具有统计学意义(P<0.05)。两组不良反应发生率差异无统计学意义。结论：射频热疗联合胸腔灌注顺铂和华蟾素明显提高了乳腺癌致恶性胸腔积液的治疗效果,患者的生存质量得到明显改善,是一种具有临床应用价值的治疗方法。     

Long-term Efficacy of Microwave Hyperthermia Combined with Chemoradiotherapy in Treatment of Nasopharyngeal Carcinoma with Cervical Lymph Node Metastases

Objective: The long-term efficacy of microwave hyperthermia combined with chemoradiotherapy in treatingnasopharyngeal carcinoma (NPC) with metastatic foci in cervical lymph nodes was evaluated. Methods: A totalof 154 cases of N2 or N3 stage NPC were randomized into two groups: hyperthermia group (76 cases) and controlgroup (78 cases). Both received cisplatin chemotherapy and radiotherapy. In addition, the hyperthermia groupfurther received microwave hyperthermia to the metastatic cervical nodes with different patterns (before or afterradiotherapy), heating temperatures (T90 < 43°C and T90 ≥ 43°C) and hyperthermia episodes (< 4 times, 4-10times and > 10 times). Results: The 3-month and 5-year complete response (CR) rates of cervical lymph nodesin the hyperthermia group were significantly higher than those in the control group. The 5-year disease-freesurvival (DFS) rate and the 3-year / 5-year overall survival rate in the hyperthermia group were also significantlyhigher. There was no significant difference in 5-year metastatic rates. In the hyperthermia group, the 3-monthand 5-year CR rates of T90 < 43°C treatment were significantly lower than with T90 ≥ 43°C treatment. TheCR rate was highest when the hyperthermia was performed 4-10 times. There were no significant differencesin 3-month and 5-year CR rates between hyperthermia before or after radiotherapy treatment. Conclusion:Microwave hyperthermia combined with chemoradiotherapy can increase local control, DFS and 3, 5-yearoverall survival rates of patients with N2 ~ N3 stage NPC. The heating temperature should be over 43°C withhyperthermia repeated 4-10 times.     

放疗联合热疗治疗原发性巨块型肝癌临床疗效观察

目的：比较应用单纯三维适形放疗与三维适形放疗联合局部热疗治疗无法手术切除的巨块型肝癌的临床疗效。方法：64例无法手术切除的巨块型肝癌患者,对照组单纯应用三维适形放疗,每周5次,每次2Gy,总剂量50-60Gy。治疗组应用三维适形放疗联合局部体外热疗,热疗在放疗后30分钟进行,每周2次,每次1小时。结果：治疗后3月内复查,对照组治疗后完全缓解（CR）1例,部分缓解（PR）20例,稳定（SD）6例,疾病进展（PD）3例,总有效率为70%。治疗组治疗后完全缓解（CR）3例,部分缓解（PR）23例,稳定（SD）6例,疾病进展（PD）2例,总有效率为76.4%。P〈0.05。放疗及热疗引起的不良反应可以耐受,而肝功能无明显损害加重。随访1年的生存期为65.5%,与对照组62.8%相比,P值〉0.05无统计学意义。结论：三维适形放疗联合热疗治疗不能手术的巨块型肝癌近期疗效确切,不良反应可耐受,是一种可以在临床应用的方法。     

复方苦参注射液及顺铂联合微波热疗治疗卵巢癌腹水的临床观察

目的：观察腹腔灌注复方苦参注射液及顺铂联合微波热疗治疗卵巢癌腹水患者的疗效及毒副反应。方法：将患者分为2组,研究组39例以915MHz 型大功率微波腹部区域热疗联合复方苦参注射液及顺铂腹腔灌注。对照组39例行复方苦参注射液及顺铂腹腔灌注,未行腹部热疗。结果：全部患者均顺利完成治疗,研究组39例中完全缓解（CR）26例,部分缓解（PR）7例,有效（CR ＋PR）率为84．62％。对照组39例中 CR 17例,PR 6例,有效率为58．98％。两组有效率比较,差异有显著性（P ＜0．05）。结论：915MHz 型大功率微波腹部区域热疗联合复方苦参注射液及顺铂腹腔灌注治疗卵巢癌腹水,疗效较单纯腹腔灌注复方苦参注射液及顺铂疗效好,未增加毒副反应,提高了治疗效果。     

三氧化二砷联合热疗对大鼠肝脏移植瘤模型凋亡相关基因表达的影响

目的 研究三氧化二砷(arsenic trioxide,As₂O₃)联合热疗对大鼠肝脏移植瘤细胞的凋亡、热休克蛋白70(Heat shock protein 70,HSP70)、p53和增殖细胞核抗原(Proliferation cell nuclear antigen,PCNA)表达的影响,探讨其诱导肿瘤细胞凋亡的可能机制。方法 建立大鼠肝脏移植瘤模型,分别对荷瘤大鼠给予生理盐水、As₂O₃、热疗及As₂O₃联合热疗,观察肿瘤生长情况,用免疫组化法检测肿瘤细胞凋亡及肿瘤组织中HSP70、p53及PCNA的表达。结果 As₂O₃ 联合热疗的抗肿瘤作用最明显,坏死及凋亡细胞数量增加。对照组HSP70、p53及PCNA阳性细胞表达率分别为30.12%±3.60%,27.64%±4.90%和74.23%±6.35%,三氧化二砷联合热疗组HSP70、p53及PCNA阳性细胞表达率分别为87.4%1±5.70%,90.06%±6.42%和22.10%±6.17%。与对照组(仅给予As₂O₃或热疗处理)比较,经As₂O₃联合热疗处理后,HSP70、p53表达显著升高(P=0.000＜ 0.05),PCNA表达则显著降低(P=0.000 ＜0.05)。结论 As₂O₃与热疗联合应用治疗大鼠肝癌有明显的协同作用;As₂O₃联合热疗通过诱导HSP70及p53的表达和降低PCNA的表达抑制肝癌细胞增殖并促进细胞凋亡。     

加温或／和化疗药对结肠癌细胞系THC—8908多药耐药基因表达的影响

用MTT法检测中药AF-7，丝裂霉素（MMC），5-氟脲嘧啶（5－Fu）在单纯用药及加温与加药共同应用，对人结肠高分化腺癌细胞系THC8908的作用，并用抗多药耐药（MDR）基因表达蛋白P170单抗及免疫组化法，检测该细胞在上述条件下（MDR）基因表达的异同。结果发现：1）加温可增强AF－7、MMC和5－Fu对肿瘤细胞的杀伤作用。2）免疫组化染色揭示，正常培养条件下该细胞MDR为中度表达，经加142．5℃1小时再培养72小时其MDR则不表达。单独用药各组均为中度表达，而加温与加药共同应用组均为低度表达，且MMC组MDR表达的阳性细胞数高于AF－7组。研究证明加温能明显抑制MDR基因表达，从而提高化疗效果。     

节拍式化疗联合微波热疗对晚期卵巢癌患者血管生成的影响及疗效观察

目的 研究节拍式化疗联合微波热疗对晚期卵巢癌患者血管生成的影响及临床疗效.方法 选择卵巢癌患者63例,随机分为观察组和对照组,观察组患者接受节拍式化疗联合微波热疗,对照组患者接受标准化疗.分别于化疗前后测定患者外周血和腹腔积液中的VEGF蛋白浓度,评估对血管生成的影响.对比两组的近期疗效、生活质量改善情况及不良反应发生情况.结果 化疗后,观察组的外周血和腹腔积液中VEGF浓度显著低于对照组(t=11.624,P=0.007&t=21.470,P=0.002);观察组总有效率为87.50%,显著高于对照组总有效率62.50%(t=4.585,P=0.032);观察组总有效改善率为77.42%,显著高于对照组的总有效改善率48.39%(t=4.729,P=0.030);观察组的不良反应发生情况显著少于对照组(P<0.05).结论 节拍式化疗联合微波热疗能显著抑制肿瘤新生血管的生成,显著改善患者的近期疗效及生活质量,且不良反应较少.     

多西他赛联合腹腔热灌注化疗加热疗治疗晚期卵巢癌

  目的  观察多西他赛联合腹腔内顺铂热灌注化疗加热疗治疗晚期卵巢癌的疗效与不良反应。   方法  无法手术及复发晚期卵巢癌患者83例,随机分成两组:热疗组42例,行多西他赛静脉化疗后即刻行腹腔内顺铂热灌注化疗并加腹部局部射频热疗;对照组41例,单纯给予多西他赛静脉化疗加腹腔内顺铂热灌注化疗。   结果  热疗组和对照组的总有效率分别是81.0%和58.1%,其中总有效率显著提高（P < 0.05）,腹水控制率分别为78.3%和66.7%,CA125下降率分别为84.2%和61.5%（P < 0.05）,主要不良反应为消化道不良反应及骨髓抑制,无显著性差异。   结论  多西他赛联合顺铂腹腔内灌注加热疗明显提高晚期卵巢癌的疗效,不增加不良反应,值得进一步推广。      

多西他赛联合腹腔热灌注化疗加热疗治疗晚期卵巢癌

目的探讨多西他赛联合腹腔热灌注化疗加热疗治疗晚期卵巢癌患者的临床疗效。方法选取2011年1月至2012年12月收治的80例晚期卵巢癌患者为研究对象,依据随机数字法分为试验组和对照组。对照组给予多西他赛联合腹腔热灌注化疗,试验组在对照组的治疗基础上给予热疗,观察两组患者的临床疗效和不良反应。结果试验组总有效率(82.5%)显著高于对照组总有效率(60.0%),两组差异有统计学意义(P<0.05)。试验组白细胞减少、恶心与呕吐、消化道反应、肝功能损害的发生率均低于对照组,差异均有统计学意义(均P<0.05)。结论应用多西他赛联合腹腔热灌注化疗加热疗治疗晚期卵巢癌可提高临床疗效,不良反应少,治疗安全性高,值得临床应用。     

热疗联合同步放化疗治疗局部晚期宫颈癌的临床观察

目的探讨内生场热疗联合同步放化疗治疗晚期宫颈癌的疗效、不良反应以及对免疫功能的影响。方法选取60例中晚期宫颈癌患者,随机分为对照组和试验组,对照组患者给予同步放化疗;试验组患者在对照组的基础上给予内生场热疗,2次/周,共治疗8次,观察疗效、不良反应及免疫功能。结果 60例患者均完成治疗,对照组患者总有效率(CR+PR)为60.0%,试验组患者总有效率(CP+PR)为86.7%,两组差异有统计学意义(P<0.05);2年总生存率(OS)差异有统计学意义。不良反应主要为胃肠道反应和骨髓抑制,患者均可以耐受,其中试验组患者皮下脂肪硬结2例(6.67%),经常规治疗后痊愈。两组患者严重不良反应比较,差异无统计学意义(P>0.05)。试验组患者T淋巴细胞免疫功能及NK细胞免疫功能较对照组改善,差异有统计学意义(P<0.05)。结论内生场热疗联合同步放化疗能提高局部晚期宫颈癌的局部控制率,延长生存时间,改善患者免疫功能,不良反应轻,患者耐受性良好。     

Cervical cancer: radiotherapy and hyperthermia.

BACKGROUND: For many years, the standard treatment of advanced cervical cancer has been radiotherapy (RT), including brachytherapy. The achievement of locoregional tumour control is essential for cure. Results of RT in early stages are reasonably satisfactory, but locoregional failure rates for stage IIIb and IVa are high. In several randomized trials, the addition of hyperthermia (HT) to RT has been investigated. RANDOMIZED TRIALS: The Dutch Deep Hyperthermia Trial was completed in 1996. In this trial a beneficial effect of additional hyperthermia was clearly demonstrated. Three-year locoregional control and overall survival rates were significantly higher in the RT + HT group than in the RT alone group, while radiation toxicity was not affected. Cost-per-life-year-gained was less than 4,000 Euros. The results of this trial have led to the acceptance of RT plus HT as standard treatment for advanced cervical cancer in the Netherlands. Five trials conducted in Asia have been published, of which three showed significant better complete response, locoregional tumour control and/or disease-free survival rates. One trial showed a trend of better locoregional tumour control and one did not show any benefit. CONCLUSION: Hyperthermia added to standard radiotherapy of locally advanced cervical tumours results in considerable therapeutic gain and is cost-effective. For a beneficial effect, the use of an adequate heating technique is an important requirement.     

内生场热疗治疗癌性疼痛的临床分析

目的观察内生场热疗对癌性疼痛的临床疗效。方法65例癌症患者随机分两组：治疗组（热疗＋化疗）31例,采用NRL－001型内生场热疗机透热治疗,每周2次,每次60分钟,12次（6周）为1个观察疗程,同时进行化疗,方案同对照组;对照组（单纯化疗）34例,选用亚叶酸钙注射液200mg／m^2,5－氟尿嘧啶注射液500mg／m^2,顺铂注射液20mg,每日1次,连用五天,21天为1个周期,2个周期（6周）为1个观察疗程。结果6周后观察结果,治疗组与对照组止痛有效率分别为90．32％和55．88％,两组间差异显著,具有统计学意义（P〈0．01）;治疗组与对照组生活质量改善总有效率分别为93．55％和47．05％,两组间差异显著,具有统计学意义（P〈0．01）。结论内生场热疗能有效缓解恶性肿瘤的癌性疼痛,提高生活质量。     

Combination of microwave hyperthermia with epirubicin inhibits the proliferation and induces the apoptosis of breast cancer cells北大核心CSCD

Objective: To investigate the effects of microwave hyperthermia in combination with epirubicin on the growth of orthotopic breast transplantation tumor in BALB/c mice and the proliferation of murine breast cancer 4T1 cells and human breast cancer MDA-MB-231 cells, and to explore their possible mechanisms. Methods: The 4T1 cells were injected into mammary fat pad of female BALB/c mice to establish the orthotopic breast transplantation tumor model. The tumor-bearing mice were treated with microwave hyperthermia, epirubicin and microwave hyperthermia in combination with epirubicin, respectively. The breast tumor volume and weight and the number of lung metastatic nodes in mice were observed. The 4T1 and MDA-MB-231 cells were treated with microwave hyperthermia, epirubicin and microwave hyperthermia in combination with epirubicin, respectively. Then the cell proliferation and apoptosis were detected by MTS assay and FCM method, respectively. The change of phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway and the expressions of apoptosis-related proteins were detected by Western blotting. Results: The tumor volume (P < 0.05) and weight (P < 0.05)and the number of lung metastatic nodes (P < 0.01) in mice in microwave hyperthermia in combination with epirubicin group were all smaller than those in the control group (the tumor-bearing mice didn't receive any treatment). The proliferation of breast cancer 4T1 and MDA-MB-231 cells in microwave hyperthermia in combination with epirubicin group was inhibited and the apoptosis was induced (all P < 0.05). Combination of epirubicin with microwave hyperthermia suppressed the activation of mTOR in 4T1 and MDA-MB-231 cells (both P < 0.05) and up-regulated the expressions of apoptosis-related proteins (all P < 0.05). Conclusion: Combination of microwave hyperthermia with epirubicin can suppress the growth and metastasis of breast cancer. This effect may be associated with the down-regulation of mTOR pathway and the up-regulation of apoptosis-related protein expressions. Copyright © 2018 by TUMOR. All rights reserved.     

高频热疗联合腔内化疗治疗藏族恶性胸腔积液患者的临床观察

目的：观察高频热疗联合腔内化疗治疗藏族恶性胸腔积液患者的疗效和毒副反应。方法57例藏族恶性胸腔积液患者随机分为2组,尽可能排尽胸腔积液后,治疗组29例患者给予顺铂胸腔内灌注,然后进行高频热疗;对照组28例患者只给予顺铂胸腔内灌注。结果治疗组总有效率为86.21%,高于对照组的57.14%（χ2=5.532,P=0.019）。治疗组生活质量改善明显优于对照组（χ2=6.339,P=0.042）。结论热疗高频热疗联合腔内化疗对恶性胸腔积液疗效确切,安全性高。