Blocking the Glycolytic Pathway Sensitizes Breast Cancer to Sonodynamic Therapy

Inhibition of the increased aerobic glycolysis in cancer cells is a promising methodology for various malignant tumor therapies but is limited by systemic toxicity, at least in part. Recent studies suggest that dual restriction of glycolysis and mitochondrial function may overcome this issue. Sonodynamic therapy (SDT), a prospective therapeutic modality for cancers, has been reported to induce mitochondria-dependent cell damage. Here, we investigated the combined effect of SDT and 2-deoxyglucose (2DG), an anti-glycolytic agent, on breast cancer both in vitro and in vivo. In vitro, we found that, compared with a single treatment, SDT + 2DG co-treatment significantly decreased cell viability and increased cell apoptosis. Moreover, the generation of reactive oxygen species was enhanced and mitochondrial membrane potential (MMP) was reduced after SDT + 2DG co-treatment. Furthermore, the oxidative phosphorylation was also restrained after SDT + 2DG co-treatment, further to cause the blockage of ATP provision. In vivo, SDT + 2DG markedly reduced tumor volume and weight, consistent with the in vitro findings. Furthermore, toxicology tests concurrently indicated that the dosages of sinoporphyrin sodium and 2DG were comparatively tolerable. Generally, these results indicated that SDT + 2DG combination therapy may be an available, promising therapy for highly metastatic breast cancer.     

Sonodynamically Induced Anti-tumor Effect of 5-Aminolevulinic Acid on Pancreatic Cancer Cells

Sonodynamic therapy (SDT), a promising modality for cancer treatment, involves the synergistic interaction of ultrasound and some chemical compounds termed sonosensitizers. However, its effect on pancreatic cancer cells remains unclear. In our study, we sought to identify the cytotoxic effects of ultrasound-activated 5-aminolevulinic acid on human pancreatic cancer Capan-1 cells. Cell viability was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) analysis; mitochondrial membrane potential was assessed using the fluorescent probe jc-1; apoptosis was evaluated by flow cytometry; cell morphology was investigated by scanning electron microscopy; apoptosis-related protein expression was analyzed by Western blot assay. We found that SDT significantly decreased the survival rate of cells, and this effect increased with 5-aminolevulinic acid concentration and ultrasound exposure time. The mechanism underlying the effect of SDT involves, in part, the induction of a conspicuous loss in mitochondrial membrane potential and, in part, the induction of apoptosis through upregulation of Bax expression, downregulation of Bcl-2 and increased activation of procaspase-3. These results indicate that the ultrasonically induced cell killing effect could be enhanced by 5-ALA and that the mitochondrial pathway might be involved in the cell damage process. We conclude that SDT is a promising new methodology for pancreatic cancer treatment.     

Sonodynamic Therapy for Malignant Glioma Using 220-kHz Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound and 5-Aminolevulinic acid

Sonodynamic therapy (SDT) is used to treat various malignancies and can be applied to brain tumors using a transcranial magnetic resonance imaging-guided focused ultrasound (TcMRgFUS) device. This study investigated the efficacy of 220-kHz TcMRgFUS combined with 5-aminolevulinic acid (5-ALA) on malignant glioma in vitro and in vivo. F98 cells were irradiated with focused ultrasound (FUS) (4000 J, 20 W, 240 s, 100% duty cycle, target medium temperature <40°C) after treatment with 200 µg/mL 5-ALA, and cell viability and apoptosis were evaluated with the water-soluble tetrazolium-1 assay, triple fluorescent staining and Western blot analysis 20 h later. The anti-tumor effects of 5-ALA combined with FUS (500 J, 18 W, 30 s, 100% duty cycle, 10 repeats, target tissue temperature ≤42°C) were assessed on the basis of changes in tumor volume determined by MRI and histopathological analysis before and after treatment. The FUS/5-ALA combination reduced cell viability by inducing apoptosis and suppressed tumor proliferation and invasion as well as angiogenesis in vivo, while causing minimal damage to normal brain tissue. SDT with 220-kHz TcMRgFUS and 5-ALA can be safely used for the treatment of malignant glioma.     

5-氨基酮戊酸光动力疗法治疗尖锐湿疣患者的疗效观察

目的:分析5-氨基酮戊酸光动力疗法治疗尖锐湿疣患者的疗效观察。方法:选取2017年3月～2019年4月收治的尖锐湿疣患者58例作为研究对象,以随机数字表法分为对照组和治疗组,各29例。对照组予以电离子手术治疗,治疗组予以5-氨基酮戊酸光动力疗法治疗。比较两组总体治疗效果、治疗前后HPV6/11型DNA载量及复发情况。结果:治疗3个月后,治疗组HPV6/11型DNA载量低于对照组,差异有统计学意义(P0.05);治疗组总有效率高于对照组,差异有统计学意义(P0.05);治疗组总复发率低于对照组,差异有统计学意义(P0.05)。结论:采用5-氨基酮戊酸光动力疗法治疗尖锐湿疣患者,可降低患者HPV病毒载量,保证治疗效果实现最优化,降低复发率。     

合并糖尿病对转移性肝癌介入治疗安全性及疗效的影响

目的：评估糖尿病对转移性肝癌患者行经动脉化疗栓塞（transarterial chemoembolization,TACE）的安全性及疗效的影响。方法：对临床诊断明确的54例转移性肝癌合并糖尿病患者（A组）及62例转移性肝癌无糖尿病患者（B组）的术前空腹血糖（其中A组每天术前均检测3餐前血糖,并通过口服降糖药、皮下注射或静脉滴注胰岛素将血糖控制在安全范围）、术后严重的并发症（包括肝脓肿、肝性脑病、糖尿病酮症酸中毒、低血糖等）发生情况、平均介入治疗次数、住院时间、平均可介入治疗期进行比较分析。结果：A组术前空腹血糖均值为（8.2±3.1）mmol·L-1,B组术前空腹血糖均值（4.5±1.4）mmol·L-1（P〈0.001）。平均介入治疗次数A组（6.3±2.1）次,B组为（9.5±2.8）次（P〈0.05）。平均住院时间A组为（11.2±3.5）d,B组为（7.8±2.6）d（P〈0.05）。平均可介入治疗期A组为（18.6±6.2）个月,B组为（23.5±4.5）个月（P〈0.05）。肝脓肿发生率A组为5.6%,B组为1.6%,经穿刺引流及抗感染药物治疗后好转。A组发生低血糖2例,肝性脑病2例,经积极治疗后好转。结论：糖尿病是影响转移性肝癌安全性及治疗疗效的一个重要因素。如果将血糖控制至安全范围内,预先去除糖尿病相关危险因素,结合血糖情况调整介入化疗栓塞方案,转移性肝癌合并糖尿病患者行TACE治疗是安全可行的。     

5-ALA介导的PDT对大鼠体内外C6胶质瘤的杀伤作用研究

目的探讨5-ALA介导的光动力对大鼠C6胶质瘤细胞体内外杀伤作用。方法MTT法探讨培育时间和5-ALA浓度对光动力效应的影响,为动物试验提供时间和剂最参考。取近皮层大鼠胶质瘤模型39只,其中PDT组12只,单纯开骨窗组9只,单用5-ALA＋开骨窗组9只,开骨窗＋激光组9只,各组处理后观察生存状态和生存期,部分大鼠行病理及透射电镜检查。结果5-ALA与C6细胞共同培育5h其介导的PDT作用达到最强;5-ALA浓度为0．8mmol／L以上时对细胞的抑制率可超过50％;电镜示PDT组瘤组织可见较多量凋亡,细胞间连接松散。结论该实验设计的大鼠近皮层模型可以很好地满足脑肿瘤动物实验的要求。5-ALA介导的PDT对体外及颅内种植C6细胞都有杀伤作用。     

5-氨基酮戊酸光动力疗法治疗肛周尖锐湿疣的疗效观察及护理

目的观察5-氨基酮戊酸光动力疗法(5-aminolevulinic acid photodynamic therapy,ALA-PDT)治疗肛周部位尖锐湿疣的疗效,并探讨其护理经验。方法采用ALA-PDT对56例肛周尖锐湿疣患者进行治疗,观察其治疗效果。结果本组患者治疗有效率94.6%,复发率为5.4%。结论治疗中使皮肤充分扩展,做好观察护理;术后做好健康教育对提高肛周尖锐湿疣的治疗效果具有重要意义。     

利声显在超声导向植入式微波留置固化治疗肝癌时 的血管定位和疗效判断价值

目的，探讨在超声导向植入式微波留置固治疗肝癌时，应用利声显作血管树定位和治疗后判断疗效的价值。方法 28例肝癌，作44例次微波凝固治疗，治疗前应用利声显超声造影，显示肿瘤内血管树，以血管树主干作为凝固治疗的重点，治疗后再次利声超声造影，观察肿瘤内血流变化，判断疗效，结果 44例次均清晰显示肿瘤内血管树主，并以此作为凝固治疗的重点，经复查随访肿瘤区内未发现血流，结论 以利声显超声造影显示的血管树主干作为凝固治疗的重点，经复查随访肿瘤区内均未发现血流，结论 以利声显超声造影显示的血管树主干作为凝固治疗的重点，可提高疗效，建议将利声显造影多普勒检查作为判断微波凝固治疗疗效的金标准。     

肝癌介入治疗病人应对方式及影响因素调查

目的 :探讨肝癌介入治疗病人的应对方式及影响因素。方法 :应用Jalowiec应对方式量表和病人一般资料问卷 ,对 83例肝癌介入治疗病人的应对方式及其影响因素进行调查。结果 :乐观应对方式为本组研究对象应用最多的方式 ,其次为面对、寻求支持、依赖自我、宿命、逃避、姑息和情感应对方式。性别、婚姻、职业、医疗费用支付方式对病人采取各种应对方式有影响 ;男性比女性更多地应用了姑息应对、依赖自我应对 (P <0 .0 5 )。结论 :肝癌介入治疗病人采用了多种应对方式和应对措施 ,护理人员应重视评估病人应对方式和应对措施的应用情况 ,根据病人的特点 ,指导和帮助病人采用积极的应对方式 ,有效地缓解各方面的压力 ,提高生活质量。     

肝动脉碘油栓塞化疗联合门静脉灌注化疗治疗中晚期肝癌

对17例原发性和转移性肝癌进行了肝动脉碘油栓塞化疗联合经皮门静脉穿刺灌注化疗。治疗后82．4％病人肿瘤缩小，显效41．2％，有效41．2％。一年生存率76.4％，二年生存率52．9％，三年生存率11.8％。40％病人甲胎蛋白明显下降。动、门脉联合治疗组明显优于单纯肝动脉栓塞化疗组。对本法的价值，门静脉插管途径，适应症和禁忌症进行了探讨。     

肝纤维化时基质金属蛋白酶-2及其组织抑制因子的表达

目的：了解基质金属蛋白酶-2（MMP-2）及其组织抑制因子（TIMP-2）在不同病因致有肝纤维化病理阶段中的变化。分析MMP-2/TIMP-2与肝病理损害的关系。方法：用免疫组织化学（LsAB法）,在正常肝组织,慢活肝伴早期肝纤维化,肝癌伴早期肝纤维化、胆汁性肝硬化、坏死后性肝硬化病例中MMP-2及TIMP-2的联合检测,行半定量研究。结果：正常肝组织MMP-2/TIMP-2的比值高于病肝组;早期肝纤维化组MMP-2/TIMP-2比值高于肝硬化组;早期肝纤维化组组间,肝硬化组组间MMP-2/TIMP-2比值无显著差异。结论：早期肝纤维化MMP-2表达相对增高,对肝纤维化的始动和进展起重要作用。肝硬化时TIMP-2表达明显增高,抑制MMP-2,细胞外基质（ECM）降解障碍而大量沉积,加重肝病理损害。     

Sonodynamically Induced Antitumor Effects of 5-Aminolevulinic Acid and Fractionated Ultrasound Irradiation in an Orthotopic Rat Glioma Model

The sonodynamically induced selective antitumor effects of 5-aminolevulinic acid (5-ALA) on a C6 glioma that was implanted in a rat brain were evaluated. One week after the inoculation of the brains with the C6 rat glioma cells, glioma development was monitored using a 1.5 T MRI. Brains both with and without intravenous administration of 5-ALA (60 mg/kg body weight) or Radachlorin (40 mg/kg body weight) were insonated by a 1 MHz ultrasound at a dose of 2.65 W/cm². Irradiation was performed in a fractionated manner to avoid any thermal effects in the tissue due to the focused ultrasound; 16 min of irradiation were followed by a 3 min recess, then 4 min of resumed irradiation. Mean tumor sizes, measured after the rats were sacrificed 2 weeks post treatment, were 122.48 ± 39.64 mm³ in sham-operated rats, 87.42 ± 21.40 mm³ in rats receiving ultrasound without 5-ALA, 10.50 ± 8.20 mm³ in rats receiving ultrasound with 5-ALA, and 56.42 ± 12.48 mm³ in rats receiving ultrasound with Radachlorin. The tumor size was significantly smaller in the therapy group receiving sonodynamic 5-ALA than in any of the other groups (p < 0.05). This experimental rat model showed that sonodynamic therapy can be useful in the treatment of deep-seated malignant gliomas.     

原发性肝癌患者介入治疗前后血清E-cad和SIL-2R检测的临床意义

目的 分析32例原发性肝癌患者介入治疗前后血清上皮钙粘蛋白（E-cad）和SIL-2R含量的变化及临床意义。方法 采用酶联法测定血清上皮钙粘蛋白和SIL-2R含量,并与35例正常对照作对比。结果 原发性肝癌患者介入治疗前血清上皮钙粘蛋白和SIL-2R水平显著高于对照组（P〈0．01）,介入治疗后6个月复发者血清上皮钙粘蛋白和SIL-2R水平持续异常,未复发者血清上皮钙粘蛋白和SIL-2R水平恢复正常。结论 E-cadSIL-2R的变化与原发性肝病病情和     

Estimating the Delivery Efficiency of Drug-Loaded Microbubbles in Cancer Cells with Ultrasound and Bioluminescence Imaging

The application of drug-loaded microbubbles (MBs) in combination with ultrasound (US), which results in an increase in capillary permeability at the site of US-sonication-induced MB destruction, may be an efficient method of localized drug delivery. This study investigated the mechanism underlying the US-mediated release of luciferin-loaded MBs through the blood vessels to targeted cells using an in vivo bioluminescence imaging (BLI) system. The luciferin-loaded MBs comprised an albumin shell with a diameter of 1234 ± 394 nm (mean ± SD) and contained 2.48 × 10⁹ bubbles/mL; within each MB, the concentration of encapsulated luciferin was 1.48 × 10⁻¹⁰ mg/bubble. The loading efficiency of luciferin in MBs was only about 19.8%, while maintaining both the bioluminescence and acoustic properties. In vitro and in vivo BLI experiments were performed to evaluate the US-mediated release of luciferin-loaded MBs. For in vitro results, the increase in light emission of luciferin-loaded albumin-shelled MBs after destruction via US sonication (6.24 ± 0.72 × 10⁷ photons/s) was significantly higher than that in the luciferin-loaded albumin-shelled MBs (3.11 ± 0.33 × 10⁷ photons/s) (p < 0.05). The efficiency of the US-mediated release of luciferin-loaded MBs in 4T1-luc2 tumor-bearing mice was also estimated. The signal intensity of the tumor with US destruction at 3 W/cm² for 30 s was significantly higher than without US destruction at 3 (p = 0.025), 5 (p = 0.013), 7 (p = 0.012) and 10 (p = 0.032) min after injecting luciferin-loaded albumin-shelled MBs. The delivery efficiency was, thus, improved with US-mediated release, allowing reduction of the total injection dose of luciferin.     

超声引导下微波介入治疗大肝癌的实验研究及临床应用

目的进一步探讨超声引导下微波治疗大肝癌的可行性和疗效。方法采用分次多点多部位由深到浅低功率长时间分段微波凝固,对10个65斤重的猪肝和2只狗进行了实验研究;60例大肝癌患者进行了超声引导下微波治疗。结果微波治疗后两个或多个坏死区叠加,凝固坏死区加大。离体猪肝坏死区达到6cm×6cm,狗肝坏死区为5cm×6cm。所有病例治疗后肿块缩小,肿瘤内血流消失或减少;22例CT检查,肿块缩小,18例无强化;28例超声引导下活检大片坏死。治疗后全身情况好转,AFP和肝功能改善,生活质量提高。无严重并发症发生。随访3～28个月,51例存活。结论实验研究表明改进微波治疗方法,坏死区加大,超声引导微波治疗大肝癌也有较好的疗效。     

音乐干预对小细胞肺癌患者抑郁状态及Th1／Th2免疫状态的影响

目的：探讨音乐干预对小细胞肺癌并发抑郁患者抑郁状态的疗效及对辅助性T细胞亚群（Th1／Th2）免疫反应状态的影响。方法：小细胞肺癌并发抑郁患者72例,随机分为音乐组和常规组各36例,并另设正常组36例。音乐组和常规组均给予常规化疗和口服阿米替林片治疗,音乐组同时配合音乐干预。治疗前后采用汉密尔顿抑郁量表（HAMD）作为抑郁评价工具,用酶联免疫吸附法检测外周血中Th1型细胞因子白细胞介素2（IL-2）、7-干扰素（IFN-7）和Th2型细胞因子白细胞介素4（IL-4）、白细胞介素10（IL-10）的浓度及评价I临床疗效。结果：治疗6及12周时音乐组和常规组与治疗前比较,患者HAMD评分及血中IL-4、IL-10浓度持续下降,IL-2、IFN-7浓度明显升高,音乐组表现更明显;12周时音乐组IL-2和IL-4浓度均接近正常组,常规组与正常组比较差异仍有统计学意义（P〈0.05）。临床疗效比较,音乐组治愈、显效率及总有效率均明显高于正常组（P〈0.01）。结论：音乐干预能减轻或消除小细胞肺癌并发抑郁患者的不良心理反应,调节和改善Th1／Th2细胞因子失衡的免疫状态。     

表皮生长因子对癌细胞Colo26、Hep-2化疗增效作用的研究

目的：通过体外细胞实验观察表皮生长因子（EGF）对化疗药物的增效作用,并探讨EGF对化疗增效的可能机制。方法：选择Colo 26、Hep-2为靶细胞,采用MTT比色分析法观察EGF对癌细胞株体外增殖的最佳剂量及时间效应。通过免疫细胞化学染色测定细胞核增殖抗原（PCNA）指数,用流式细胞仪做细胞周期分析,初步探讨EGF对癌细胞株化疗敏感性的影响。用免疫细胞化学染色测定癌细胞的EGF受体（EGFR）表达,来初步探讨EGFR是否与EGF化疗增效作用有关。结果：①Colo26癌细胞株：实验组的每个浓度与对照组比较,光吸收值无明显差异（P〉0．05）;实验组的24、48、72h与对照组比较,光吸收值有差异（P〈0．05）;实验组的PCNA指数与对照组比较,无差异（P〉0．05）;实验组S、G2／M期细胞及细胞增殖指数（PI）与对照组比较,PI减少但无差异（P〉0．05）。②Hep-2癌细胞株：实验组的0．01、0．10ng／ml浓度与对照组比较,有显著差异（P〈0.01）,1．00、10．00、100．00浓度有差异（P〈0．05）;实验组的24、48、72h与对照组比较,光吸收值有差异（P〈0．05）;实验组的PCNA指数与对照组比较,有显著差异（P〈0．01）;实验组S期细胞及PI与对照组比较,PI明显减少（P〈0．01）,其中DDP对Hep-2作用尤为突出,而未增加G2／M期细胞阻滞。③Hep-2的EGFR表达阳性细胞率明显高于Colo 26,差异显著（P〈0．01）。结论：EGF可以提高化疗药物对colo26、Hep-2细胞株的杀伤作用,其化疗增效作用以EGFR作用为前提,且有一定的剂量和时间效应。     

The effect of folic acid and 5-formyltetrahydrofolic acid on folate-deficient HEp 2 cells in culture

Folic acid has less effect than 5-formyltetrahydofolic acid (folinic acid) in the alleviation of folate deficiency in cultured HEp 2 cells as measured by the deoxyuridine suppression test. Folic acid inhibits the metabolism of 5-formyltetra-hydrofolic acid in vitro, is contraindicated in some cases of clinical folate deficiency and may be inappropriate in others.     

5-氨基酮戊酸光动力联合胶原蛋白贴治疗中重度痤疮效果观察

目的探讨10％5-氨基酮戊酸光动力联合胶原蛋白贴治疗中重度痤疮的临床疗效。方法选择我院2010年1月-2011年6月收治的160例中重度痤疮,按照数字编号随机分为治疗组与对照组。治疗组80例,予10％ 5-氨基酮戊酸光动力联合胶原蛋白贴治疗;对照组80例,仅予10％5-氨基酮戊酸光动力治疗,8周后进行总体评估,并记录两组治疗过程中出现的不良反应。结果治疗组痊愈率50．63％,总有效率86．08％,对照组痊愈率40．51％,总有效率72．15％,两组痊愈率比较差异无统计学意义（x2=1．29,P〉0．05）,总有效率比较差异有统计学意义（x2=4．63,P〈0．05）。结论10％5-氨基酮戊酸光动力联合胶原蛋白贴治疗中重度痤疮可提高疗效,并减少不良反应。     

反义P^53基因和mdm2基因对裸鼠致瘤性的影响

目的;研究反义Ｐ＾５３基因和ｍｄｍ２基因对裸鼠致瘤性的影响,为肺腺癌基因治疗提供新思路和新方法。方法：将含有反义Ｐ＾５３基因和ｍｄｍ２基因及空载体的逆转录表达载体通过脂质体介导分别转染ＧＬＣ－８２细胞,经Ｇ４１８筛选得到抗性克隆。采用流式细胞仪测定细胞周期,软琼脂培养集落形成试验观察集落形成。