表阿霉素聚氰基丙烯酸正丁酯磁性纳米粒靶向治疗裸鼠移植性肝癌

目的 观察表阿霉素聚氰基丙烯酸正丁酯磁性纳米粒(EPI-PBCA-MNPS)对裸鼠移植性肝癌的作用效果.方法 建立Bel-7402裸鼠人肝癌模型,当肿瘤体积长至20～30mm3时,将其随机分成5组:生理盐水组(NS组)、表阿霉素组(EPI组)、表阿霉素聚氰基丙烯酸正丁酯纳米粒组(EPI-PBCA-NPS组)、表阿霉素聚氰基丙烯酸正丁酯磁性纳米粒组(EPI-PBCA-MNPS组)、表阿霉素聚氰基丙烯酸正丁酯磁性纳米粒组加磁场组(EPI-PBCA-MNPS+MF组),每组10只,除生理盐水组外,其余各组按照0.002mg/g体质量或相当于40 μg/只的表阿霉素静脉注射给药,治疗2周后处死裸鼠,准确测量肿瘤大小并称重,计算瘤体积抑制率及瘤重抑制率,所有肿瘤均编号病理切片,比较治疗前后各组肿瘤细胞坏死的程度.结果 治疗后肿瘤体积抑制率、瘤重抑制率除EPI-PBCA-NPS组与EPI-PBCA-MNPS组差异无统计学意义(P>0.05)外,其余各组间差异有统计学意义(P<0.05),其中EPI-PBCA-MNP+MF组(94.26%、80.82%)显著高于其余组,差异有统计学意义(P<0.01).病理切片显示,EPI-PBCA-MNP+MF组肿瘤细胞坏死程度最重.结论 EPI-PBCA-MNPS具有良好的靶向性,在外加磁场作用下对裸鼠人肝癌模型有显著抑瘤作用.

Abstract：

Objective To observe the effect of epirubicin polybutylcyanoacrylate magnetic nanoparticles (EPI-PBCA-MNPS) on the transplanted hepatoma in nude mice.Methods Human hepatoma cell line Bel-7402 nude mice models were established and divided into 5 groups with each of 10 once gross tumor volume was up to 20-30 mm3:normal saline group (NS),epirubicin group (EPI),epirubicin polybutylcyanoacrylate nanoparticles group (EPI-PBCA-NPS),epirubicin polybutylcyanoacrylate magnetic nanoparticles group (EPI-PBCA-MNPS) and epirubicin polybutylcyanoacrylate magnetic nanoparticles+magnetic field group(EPI-PBCA-MNPS+MF).Except for NS group, the dosage of epirubicin was 0.002 mg/g body weight or 40 μg for intravenous injection.After two-weeks therapy,all nude mice models were executed and the tumor volume and weight were measured so as to calculate the volume inhibition ratio and the weight inhibition ratio.Every tumor specimen was made into pathological section and labelled with serial number for comparing neorobiosis degree in different groups before and after therapy.Results There were statistically difference among the other groups (P<0.05) in the volume inhibition ratio and the weight inhibition ratio after therapy except for EPI-PBCA-NPS and EPI-PBCA-MNPS group (P>0.05).The two ratios in the EPI-PBCA-MNP+MF group (94.26%,80.82%) were significantly more than those in other groups (P<0.01).The pathological sections demonstrated the most severe tumour neorobiosis in the EPI-PBCA-MNP+MF group.Conclusion With the additional magnetic field,EPI-PBCA-MNPS has significant anticancer effect on human hepatoma nude mice models due to its favourable magnetic targeting.     

Role of spinal cord TNF-α in the development of bone cancer pain in mice

Objective To investigate the role of spinal cord TNF-a in the development of bone cancer pain in mice. Methods Seventy-two 4-6 week old C3H/He mice weighing 18-25 g were randomly divided into 3 groups (n = 24 each) : group I sham operation (group S) ; group II bone cancer pain (group BCP) and group Ⅲ etanercept (group E). Bone cancer pain was induced by implantation of osteosarcoma NCTC 2472 cells into the intramedullary space of right femur in group II and Ⅲ . Group Ⅲ received intraperitoneal etanercept 100 μg at 3 days before and immediately before and day 3 and 6 after tumor cell inoculation. In group S culture medium α-MEM containing no cancer cell was injected instead. The paw withdrawal threshold to mechanical stimuli (PWMT) and paw withdrawal latency to thermal stimuli ( PWTL) were measured before inoculation (baseline) and at day 3, 5,7, 10, 14 after inoculation respectively. Eight animals were killed on the 7th, 10th, and 14th day after inoculation in each group. The spinal cords were removed and TNF-α mRNA expression in the spinal cord was determined by RT-PCR. Results Cancer pain was significantly attenuated by pretreatment with etanercept. The TNF-α mRNA expression in the spinal cord was significantly increased after inoculation and was significantly attenuated by pretreatment with etanercept in group Ⅲ . Conclusion Spinal cord TNF-a is involved in the development of bone cancer pain in mice.     

Role of spinal cord TNF-α in the development of bone cancer pain in mice

Objective To investigate the role of spinal cord TNF-a in the development of bone cancer pain in mice. Methods Seventy-two 4-6 week old C3H/He mice weighing 18-25 g were randomly divided into 3 groups (n = 24 each) : group I sham operation (group S) ; group II bone cancer pain (group BCP) and group Ⅲ etanercept (group E). Bone cancer pain was induced by implantation of osteosarcoma NCTC 2472 cells into the intramedullary space of right femur in group II and Ⅲ . Group Ⅲ received intraperitoneal etanercept 100 μg at 3 days before and immediately before and day 3 and 6 after tumor cell inoculation. In group S culture medium α-MEM containing no cancer cell was injected instead. The paw withdrawal threshold to mechanical stimuli (PWMT) and paw withdrawal latency to thermal stimuli ( PWTL) were measured before inoculation (baseline) and at day 3, 5,7, 10, 14 after inoculation respectively. Eight animals were killed on the 7th, 10th, and 14th day after inoculation in each group. The spinal cords were removed and TNF-α mRNA expression in the spinal cord was determined by RT-PCR. Results Cancer pain was significantly attenuated by pretreatment with etanercept. The TNF-α mRNA expression in the spinal cord was significantly increased after inoculation and was significantly attenuated by pretreatment with etanercept in group Ⅲ . Conclusion Spinal cord TNF-a is involved in the development of bone cancer pain in mice.     

纳米磁流体靶向栓塞食道曲张静脉破裂出血的研究

目的 观察纳米磁流体靶向栓塞食道曲张静脉破裂出血的止血效果及安全性.方法 将10条食道静脉曲张破裂出血动物模型(犬)随机分为栓塞治疗组和对照组,治疗组经股静脉注射吸附纤维蛋白原的磁流体10 ml,食道内磁控30 min,观察出血量及止血时间,并取食道、脑组织、肝、肺、肾、心肌进行病理学检查.结果 治疗组出血量(46±18)ml小于对照组(66±15)ml,差异有统计学意义(P＜0.05).治疗组止血时间(4.60±0.44)min小于对照组(5.00±0.52)min,差异有统计学意义(P＜0.05).病理学检查发现治疗组食道黏膜下静脉及穿支静脉血栓形成,脑组织、肝、肺、肾、心肌均未发现异位栓塞.结论 纳米磁流体可以用于食道曲张静脉破裂出血的靶向栓塞,缩短止血时间,减少出血量,避免发生异位栓塞.

Abstract：

Objective To observe the hemostasis effect and safety of targeted embolization of esophagus varix hemorrhage with nano-magnetic fluid. Methods Ten canine models of esophagus varix hemorrhage were randomly divided into embolotherapy group and control group. In embolotherapy group,10 nl nano-magnetic fluid treated with fibrinogen was injected through vena femoralis and exposed to magnetic field for 10 min. Bleeding volume and hemostasis effect were recorded. Pathological changes of the esophagus, brain, liver, lung, kidney and myocardium were observed. Results Bleeding volume in embolotherapy group (46 ±18) ml was less than in control group (66±15) ml (P＜0. 05). Hemostasis time in embolotherapy group (4.60 ±0.44) min was shorter than in control group (5.00 ±0.52) min (P ＜0.05).Thromboses were found in the submucosal vein and perforating branch vein of embolotherapy group. However, no thrombosis was found in the brain, liver, lung, kidney and myocardium. Conclusion Nano-magnetic fluid can be used for targeted embolization of esophagus varix hemorrhage to promote hemostasis and avoid allotopia thrombosis.     

完全去交感肾上腺素能神经支配对小鼠前列腺癌生物学行为的影响

Objective To investigate the effects of complete denervation of sympathetic adrenergic nerves on the biological behaviors of prostate cancer in C57BL/6 mice. Methods Fifty male C57BL/6 mice, 10 weeks old, were randomly divided into two groups. By using a micro-syringe, RM-1 cells (0. 5 ×106) were injected into bilateral dorsal prostate capsules of mice, at the same time, bilateral hypogastric sympathetic nerves of the mice were cut (experimental group) or not (control group). At the sixth day postoperation, 5 mice were sacrificed in each group every three days to observe the local growth, invasion and metastasis of prostate cancer to pelvic nodes and other organs. An immunohistochemical determination of the hypogastric nerves was made by using an antibody against tyrosine hydroxylase ( TH) , a marker for sympathetic nerves. At the 15th day, 10 mice left were fed to death to calculate the life span of tumor-bearing mice. Results The volume of the prostate was gradually increased and confirmed as prostate cancer histologically. The prostate volume in experimental group was (0. 034 ± 0. 008) , (0. 339 ±0. 040) , (0. 829 ±0. 090) , ( 1. 169 ±0. 093) cm3 on the day 6, 9, 12, 15 after operation, respectively,while that in control group was (0.034 ± 0. 008), (0. 316 ± 0. 050), (0. 824 ± 0.071), (1. 236 ±0. 103) cm3, respectively (all P ＞ 0. 05). At the 12th day, muscle tissues around the prostate invasion by prostate cancer were observed in 3 cases of experimental group and 4 cases of control group; at the 15th day, invasion of seminal vesicles and bladder was found in 4 cases of experimental group and 4 cases of control group. Three and 4 mice had metastasis of pelvic nodes at 12th day and 15th day respectively in the experimental group, and 4 and 4 respectively in control group. At the 15th day post operation, in control group, liver parenchyma metastasis and renal pelvis metastasis were observed in 1 and 1 case, respectively, while in experimental group, no distant metastasis was observed. The life span of tumor-bearing mice in the experimental and control groups was (15.80±0.84) and (16.00±0.71) days, respectively (P＞0. 05 ) . Conclusion Complete denervation of sympathetic adrenergic nerves seems to have no significant effects on the local growth, invasion and pelvic nodes metastasis of prostate cancer in C57BL/6 mice, but may have some inhibition effects on its distant metastasis.     

完全去交感肾上腺素能神经支配对小鼠前列腺癌生物学行为的影响

Objective To investigate the effects of complete denervation of sympathetic adrenergic nerves on the biological behaviors of prostate cancer in C57BL/6 mice. Methods Fifty male C57BL/6 mice, 10 weeks old, were randomly divided into two groups. By using a micro-syringe, RM-1 cells (0. 5 ×106) were injected into bilateral dorsal prostate capsules of mice, at the same time, bilateral hypogastric sympathetic nerves of the mice were cut (experimental group) or not (control group). At the sixth day postoperation, 5 mice were sacrificed in each group every three days to observe the local growth, invasion and metastasis of prostate cancer to pelvic nodes and other organs. An immunohistochemical determination of the hypogastric nerves was made by using an antibody against tyrosine hydroxylase ( TH) , a marker for sympathetic nerves. At the 15th day, 10 mice left were fed to death to calculate the life span of tumor-bearing mice. Results The volume of the prostate was gradually increased and confirmed as prostate cancer histologically. The prostate volume in experimental group was (0. 034 ± 0. 008) , (0. 339 ±0. 040) , (0. 829 ±0. 090) , ( 1. 169 ±0. 093) cm3 on the day 6, 9, 12, 15 after operation, respectively,while that in control group was (0.034 ± 0. 008), (0. 316 ± 0. 050), (0. 824 ± 0.071), (1. 236 ±0. 103) cm3, respectively (all P ＞ 0. 05). At the 12th day, muscle tissues around the prostate invasion by prostate cancer were observed in 3 cases of experimental group and 4 cases of control group; at the 15th day, invasion of seminal vesicles and bladder was found in 4 cases of experimental group and 4 cases of control group. Three and 4 mice had metastasis of pelvic nodes at 12th day and 15th day respectively in the experimental group, and 4 and 4 respectively in control group. At the 15th day post operation, in control group, liver parenchyma metastasis and renal pelvis metastasis were observed in 1 and 1 case, respectively, while in experimental group, no distant metastasis was observed. The life span of tumor-bearing mice in the experimental and control groups was (15.80±0.84) and (16.00±0.71) days, respectively (P＞0. 05 ) . Conclusion Complete denervation of sympathetic adrenergic nerves seems to have no significant effects on the local growth, invasion and pelvic nodes metastasis of prostate cancer in C57BL/6 mice, but may have some inhibition effects on its distant metastasis.     

表达端粒酶逆转录酶siRNA的溶瘤腺病毒对裸鼠肾癌移植瘤的治疗作用

Objective To investigate the antitumor effect of oncolytic adenovirus armed with small interference RNA targeting hTERT gene for renal cancer therapy. Methods Nude mice were divid-ed randomly into 4 groups (8 mice/group),and were treated by intratumoral injections of ZD55-hTERT ( an oncolytic adenovirus armed with small interference RNA targeting hTERT gene) ,ZD55-EGFP ( an on-colytic adenovirus) and Ad-hTERT (replication-defective adenovirus armed with small interference RNA targeting hTERT gene) with three consecutive daily at 7 × 108 pfu/day or treated with PBS as a control. The expression of E1A and hTERT, and apoptosis of tumor xenografts were assessed by immunohistochemi-cal technique at the 7th day after injections. The tumor volume was measured at the 50th day after injec-tions. Results The tumor volume in ZD55-hTERT treatment group ( 124.1±27.5) was significantly less than that in ZD-EGFP (499.8±77.1 ) and Ad-hTERT ( 609.0±102.5 ) treatment groups. The E 1A pos-itive expression in ZD55-hTERT treatment group was significantly higher than that in Ad-hTERT treatment group. The hTERT positive expression in ZD55-hTERT treatment group was significantly lower than that in Ad-hTERT treatment group. ZD55-hTERT treatment of tumor xenografts resulted in an increased apoptotie cell death as compared with ZD55-EGFP and Ad-hTERT treatment. Conclusion The antitumor effect of ZD55-hTERT was more potent than oneolytie adenovirus ZD55-EGFP and Ad-hTERT.     

表达端粒酶逆转录酶siRNA的溶瘤腺病毒对裸鼠肾癌移植瘤的治疗作用

Objective To investigate the antitumor effect of oncolytic adenovirus armed with small interference RNA targeting hTERT gene for renal cancer therapy. Methods Nude mice were divid-ed randomly into 4 groups (8 mice/group),and were treated by intratumoral injections of ZD55-hTERT ( an oncolytic adenovirus armed with small interference RNA targeting hTERT gene) ,ZD55-EGFP ( an on-colytic adenovirus) and Ad-hTERT (replication-defective adenovirus armed with small interference RNA targeting hTERT gene) with three consecutive daily at 7 × 108 pfu/day or treated with PBS as a control. The expression of E1A and hTERT, and apoptosis of tumor xenografts were assessed by immunohistochemi-cal technique at the 7th day after injections. The tumor volume was measured at the 50th day after injec-tions. Results The tumor volume in ZD55-hTERT treatment group ( 124.1±27.5) was significantly less than that in ZD-EGFP (499.8±77.1 ) and Ad-hTERT ( 609.0±102.5 ) treatment groups. The E 1A pos-itive expression in ZD55-hTERT treatment group was significantly higher than that in Ad-hTERT treatment group. The hTERT positive expression in ZD55-hTERT treatment group was significantly lower than that in Ad-hTERT treatment group. ZD55-hTERT treatment of tumor xenografts resulted in an increased apoptotie cell death as compared with ZD55-EGFP and Ad-hTERT treatment. Conclusion The antitumor effect of ZD55-hTERT was more potent than oneolytie adenovirus ZD55-EGFP and Ad-hTERT.     

表达端粒酶逆转录酶siRNA的溶瘤腺病毒对裸鼠肾癌移植瘤的治疗作用

Objective To investigate the antitumor effect of oncolytic adenovirus armed with small interference RNA targeting hTERT gene for renal cancer therapy. Methods Nude mice were divid-ed randomly into 4 groups (8 mice/group),and were treated by intratumoral injections of ZD55-hTERT ( an oncolytic adenovirus armed with small interference RNA targeting hTERT gene) ,ZD55-EGFP ( an on-colytic adenovirus) and Ad-hTERT (replication-defective adenovirus armed with small interference RNA targeting hTERT gene) with three consecutive daily at 7 × 108 pfu/day or treated with PBS as a control. The expression of E1A and hTERT, and apoptosis of tumor xenografts were assessed by immunohistochemi-cal technique at the 7th day after injections. The tumor volume was measured at the 50th day after injec-tions. Results The tumor volume in ZD55-hTERT treatment group ( 124.1±27.5) was significantly less than that in ZD-EGFP (499.8±77.1 ) and Ad-hTERT ( 609.0±102.5 ) treatment groups. The E 1A pos-itive expression in ZD55-hTERT treatment group was significantly higher than that in Ad-hTERT treatment group. The hTERT positive expression in ZD55-hTERT treatment group was significantly lower than that in Ad-hTERT treatment group. ZD55-hTERT treatment of tumor xenografts resulted in an increased apoptotie cell death as compared with ZD55-EGFP and Ad-hTERT treatment. Conclusion The antitumor effect of ZD55-hTERT was more potent than oneolytie adenovirus ZD55-EGFP and Ad-hTERT.     

表达端粒酶逆转录酶siRNA的溶瘤腺病毒对裸鼠肾癌移植瘤的治疗作用

Objective To investigate the antitumor effect of oncolytic adenovirus armed with small interference RNA targeting hTERT gene for renal cancer therapy. Methods Nude mice were divid-ed randomly into 4 groups (8 mice/group),and were treated by intratumoral injections of ZD55-hTERT ( an oncolytic adenovirus armed with small interference RNA targeting hTERT gene) ,ZD55-EGFP ( an on-colytic adenovirus) and Ad-hTERT (replication-defective adenovirus armed with small interference RNA targeting hTERT gene) with three consecutive daily at 7 × 108 pfu/day or treated with PBS as a control. The expression of E1A and hTERT, and apoptosis of tumor xenografts were assessed by immunohistochemi-cal technique at the 7th day after injections. The tumor volume was measured at the 50th day after injec-tions. Results The tumor volume in ZD55-hTERT treatment group ( 124.1±27.5) was significantly less than that in ZD-EGFP (499.8±77.1 ) and Ad-hTERT ( 609.0±102.5 ) treatment groups. The E 1A pos-itive expression in ZD55-hTERT treatment group was significantly higher than that in Ad-hTERT treatment group. The hTERT positive expression in ZD55-hTERT treatment group was significantly lower than that in Ad-hTERT treatment group. ZD55-hTERT treatment of tumor xenografts resulted in an increased apoptotie cell death as compared with ZD55-EGFP and Ad-hTERT treatment. Conclusion The antitumor effect of ZD55-hTERT was more potent than oneolytie adenovirus ZD55-EGFP and Ad-hTERT.     

Fe2O3纳米磁流体热疗治疗肝癌

目的　研究在一定高频交变磁场不同浓度的Fe2 O3 纳米磁流体热疗对SMMC772 1肝癌的治疗作用。方法　光学显微镜、电子显微镜观察细胞形态 ,四甲基偶氮唑蓝 (MTT )比色法检测Fe2 O3 纳米磁流体热疗 (MFH)对SMMC772 1肝癌细胞株生长的影响 ,流式细胞仪 (FCM )检测凋亡细胞 ,荷瘤鼠热疗实验检测MFH对肝癌的肿瘤体积抑制率及质量抑制率。结果　SMMC772 1细胞经Fe2 O3 纳米磁流体热疗作用后 ,细胞增殖受到明显抑制 ,细胞凋亡率明显增加 ,且与磁流体浓度呈依赖关系 ;动物实验显示纳米磁流体热疗对肝癌的体积和质量有明显的抑制作用。结论　Fe2 O3 纳米磁流体热疗能抑制肝癌SMMC772 1细胞增殖 ,促进其凋亡 ,并对肝癌显示明显的体积和质量抑制效应 ,对肝癌的治疗有一定的作用。     

载铁液固相变型PLGA植入物原位磁感应热消融裸鼠SKOV3人卵巢癌

目的制备载铁的液固相变型聚乳酸一羟基乙酸（PLGA）原位植入物（Fe-ISFIs）,观察其在超高频交变磁场下对裸鼠SKOV3人卵巢癌的消融效果。方法制备含铁质量分数40％的Fe-ISFIs,测定不同量（50、25μl）Fe-ISFIs相变后在交变磁场中5min内温度的变化,然后注入不同量（50、25肛1）Fe-ISFIs于离体牛肝中,置于交变磁场中不同时间（1、2、3、5rain）,观察牛肝消融直径,并选取最佳治疗方案。取9只荷SKOV3人卵巢癌裸鼠,于超声引导下向瘤内局部注射50肛lFe—ISFIs,之后分为2组：第1组6只裸鼠于交变磁场中照射3min,第2组3只裸鼠不进行磁性照射。治疗完成后第1组中任选3只、第2组选1只裸鼠处死,并取下肿瘤行HE及TTC染色,每日肉眼观察其余裸鼠肿瘤生长情况。结果体外加热实验结果显示,遇水发生液固相变后的Fe-ISFIs在交变磁场中温度逐渐增高,50μlFe-ISFIs较25μlFe-ISFIs加热效果显著;牛肝消融实验观察到50μlFe-ISFIs在3min内消融直径可达（1．18±0．18）cm,而25肛1Fe-ISFIs加热效果较差,5min内消融直径只有（0．94±0．10）cm;TTC染色结果显示经交变磁场照射治疗后部分肿瘤消融完全,但仍存在消融不全的肿瘤。HE染色见肿瘤组织坏死征象,肿瘤细胞出现核固缩或消失;肉眼观察第1组中肿瘤于治疗后第2天肿瘤组织开始脱落、结痂,约14天创面逐渐愈合,肿瘤组织消失（完全消融的肿瘤）;第2组中肿瘤随时间而逐渐增大。结论Fe—ISFIs结合超高频交变磁场能够在较短时间内有效消融裸鼠SKOV3人卵巢癌。     

125I粒子植入对人肝癌细胞裸鼠HepG2 移植瘤的杀伤作用及其分子机制

目的探讨不同剂量^125I粒子组织间植入对人肝癌细胞裸鼠HepG2移植瘤的杀伤作用及其分子机制。方法构建20个人肝癌细胞HepG2的裸鼠移植瘤模型,随机分为4组,每组5只。3个治疗组分别接受18.5 MBq、29.6 MBq、37.0 MBq的^125I粒子治疗,对照组不接受治疗。采用经皮肿瘤组织直接植入的方式分别将不同剂量^125I粒子植入各治疗组小鼠的瘤体内,每只小鼠瘤体内植入1粒^125I粒子。至治疗第28天处死小鼠,取肿瘤组织行常规病理学和免疫组织化学检查检测Bcl-2和Bax的表达情况。结果光镜下各治疗组肿瘤细胞呈不同程度凝固性坏死,周围广泛纤维化;对照组肿瘤细胞丰富,呈增殖样生长。免疫组织化学结果显示各治疗组中Bax的表达均高于对照组,并随^125I粒子剂量的增加而逐渐增加;各治疗组中Bcl-2的表达及Bcl-2/Bax比值均低于对照组,并随^125I粒子剂量的增加而逐渐减少。Bcl-2、Bax阳性率及Bcl-2/Bax比值在各治疗组与对照组间及各治疗组间的差异均有统计学意义（P均〈0.05）。结论^125I粒子组织间植入治疗可通过下调Bcl-2/Bax的比值促进裸鼠HepG2肝癌细胞凋亡,从而抑制肿瘤的生长;其诱导肝癌细胞凋亡的程度及抑制肿瘤生长的效果均在一定剂量范围内与剂量成正比。     

三氧化二砷对裸鼠人乳腺癌移植瘤的作用及机制

目的 探讨三氧化二砷(As2O3)对乳腺癌移植瘤的作用及其机制.方法 建立BALB/C-nu/nu裸鼠ER阴性MDA-MB-435s人乳腺癌移植瘤模型,分别以不同浓度的AS2O3、顺铂和0.9%氯化钠注射液(NS)腹腔内注射,观察移植瘤的瘤重及抑瘤率.并用免疫组化检测乳腺癌石蜡标本中PTEN和Casepase7的表达.结果 AS2O3高剂量组、AS2O3低剂量组、顺铂组均能明显抑制裸鼠皮下肿瘤的生长,抑瘤率分别为48.68%、32.80%、66.67%.用药后移植瘤组织巾PTEN和Casepase-7蛋白阳性细胞数显著增多(P＜0.05).结论 AS2O3能明显抑制乳腺癌移植瘤的生长,其作用机制可能是通过上凋PTEN和Caspase-7的表达(P＜0.05),促进细胞的凋亡来抑制人乳腺癌细胞的生长.     

塞来昔布联合依维莫司对恶性嗜铬细胞瘤裸鼠移植瘤的抑制作用

目的本研究通过观察环氧合酶2(Cox-2)抑制剂塞来昔布与哺乳动物雷帕霉素靶蛋白(mTOR)抑制剂依维莫司对大鼠嗜铬细胞瘤细胞PC12的裸鼠移植瘤生长的影响,探讨依维莫司对大鼠嗜铬细胞瘤肿瘤生长和血管生成的抑制作用。方法用大鼠嗜铬细胞瘤细胞PC12接种于裸鼠皮下,建立移植瘤模型,15d后将荷瘤裸鼠随机分为4组,每组12只,分别为依维莫司组(依维莫司灌胃1mg/kg)、塞来昔布组(塞来昔布100mg/kg灌胃)、联合组(依维莫司1mg/kg+塞来昔布100mg/kg灌胃)、对照组(生理盐水灌胃10mL/kg),用药3周,第4周后测量裸鼠移植瘤的体积变化以及裸鼠的生存时间,采用免疫组化方法检测肿瘤组织中血管内皮生长因子(VEGF)的表达,采用Western blotting法检测肿瘤组织中VEGF的表达。结果第4周时移植瘤体积:对照组为(4 159.72±651.84)mm3,依维莫司组为(2 816.49±332.05)mm3,塞来昔布组为(4 018.38±527.46)mm3,联合组为(1 035.28±177.30)mm3,联合组与前3组均存在显著性差异(P0.01)。平均生存时间:对照组(23.3±2.8)d,依维莫司组(36.8±3.6)d,塞来昔布组(26.4±2.4)d,联合组(45.9±4.5)d,用Kaplan-meier,Log-rank方法分析,联合组与前三组的生存函数的差异有统计学意义(P0.05)。实验组肿瘤组织的VEGF表达明显低于对照组(P0.05)。结论塞来昔布联合依维莫司对大鼠嗜铬细胞瘤裸鼠移植瘤有明显抑制作用,并可降低肿瘤组织中VEGF的表达。     

Fe_3O_4磁纳米介导磁感应治疗Wistar大鼠Walker-256肿瘤

目的探讨Fe3O4磁性纳米微球磁感应对Wistar大鼠Walker-256肿瘤的治疗作用。方法荷瘤鼠随机分为NS组（注入生理盐水而不接受磁场处理）、MF组（注入磁流体而不接受磁场处理）、MFH1组（注入磁流体在交变磁场中治疗1次）、MFH2组（治疗2次）和MFH3组（治疗3次）,共5组。治疗温度控制在50～55℃,分别观察肿瘤体积抑制率和生存期,以及肿瘤的病理改变。结果MFH2组和MFH3组的肿瘤在2周内有明显的肿瘤体积抑制作用,肿瘤体积抑制率分别为（65.0±3.5）%、（71.6±4.2）%。与NS组（35.5±5.6）d比较,MFH3组（41.9±6.5）d和MFH2组（42.1±5.0）d的生存期延长,差异有统计学意义（q=4.386,P〈0.05;q=4.558,P〈0.05）;MFH1组（39.0±5.3）d和MF组（36.1±6.6）d的生存期差异无统计学意义（q=2.406,P〉0.05）。NS、MF组肿瘤表面光滑,小灶性坏死区;癌细胞密度大,核仁明显,易见核分裂相。MFH2和MFH3组瘤内大片坏死残留的无结构红染物质,或空洞,部分胞核有固缩、碎裂及崩解。结论Fe3O4纳米磁流体介导的磁热疗能抑制大鼠Walker-256皮下肿瘤增殖。     

慢病毒介导的microRNA-21-siRNA对肝癌细胞系HepG2生物学行为的影响

目的 通过构建慢病毒介导( lentivirus,LV)的microRNA-21-siRNA,探讨下调microRNA-21对肝癌细胞系HepG2生物学行为的影响.方法 针对目标序列合成特异性siRNA干扰片段并克隆入慢病毒载体pGCSIL-GFP,将重组microRNA-21-RNAi-LV转染肝细胞癌HepG2.体外设为干扰组(microRNA-21 -siRNA,SI组)、阴性对照组(negative control,NC组)和正常组(normal,N组);分别采用聚合酶链反应方法检测microRNA-21目的基因的表达的情况;用噻唑蓝比色法检测增殖情况、transwell小室迁移实验检测迁移情况、Hochest33258凋亡实验检测凋亡情况.体内实验设为SI组和NC组,观察反义microRNA-21对裸鼠移植瘤生长的影响.结果 (1)micmRNA-21 -RNAi-LV可显著降低microRNA-21的表达.(2) MTT实验96h后SI组增殖能力显著低于NC组和N组(P=0.0031,P＜0.05).(3)迁移能力减弱(P =0.0004,P＜0.05).(4)SI组细胞凋亡明显增加,促凋亡基因caspase3基因表达上调(P =0.0002,P＜0.05).(5)各组裸鼠皮下肿瘤生长比较差异无统计学意义(P=0.0624,P＞0.05).结论 microRNA-21 -siRNA通过抑制microRNA-21的表达抑制细胞增殖,促进细胞凋亡,降低其迁移能力.     

纳米磁微粒体介导热疗治疗肝癌

纳米磁微粒体在交变磁场中可产生热量,利用该特性可研制一种治疗肝癌的绿色疗法。文章综述了纳米磁微粒体材料的特点、交变磁场的研制、纳米磁微粒体介导热疗治疗肝癌的动物实验及临床研究的进展以及尚需要解决的问题。     

干扰素-α抑制高转移潜能人肝癌裸鼠肝细胞生长因子及血管内皮生长因子的表达

目的 观察干扰素-α(IFN-α)对高转移潜能人肝癌裸鼠模型中血管内皮生长因子(VEGF)、肝细胞生长因子(HGF)mRNA表达的影响.方法 应用绿色荧光蛋白转染的人高转移肝癌细胞株HCC-LM3建立高转移潜能人肝癌裸鼠模型LCI-D20,种植后第2天开始分别使用IFN-α 1.5×104 U/(kg·d)(治疗组,n=12)或生理盐水(对照组,n=12)皮下注射,28 d后处死裸鼠,比较肝脏肿瘤的大小和肝内转移,免疫组织化学检测肿瘤微血管密度(MVD),实时荧光定量聚合酶链反应(PCR)检测肿瘤HGF和VEGF表达的变化.结果治疗组、对照组的肝内肿瘤大小分别为(0.11±0.03)cm3、(0.99±0.37)cm3(P<0.05);肝内转移率分别为33.3%(4/12)、83.3%(10/12)(P<0.05);肝内转移数目分别为0.67±0.31个比1.91±0.43个(P<0.05);肿瘤内MVD分别为3.19±0.52、4.85±0.72(P<0.05);肿瘤VEGF mRNA表达(-△CT)分别为-8.16±0.54、-6.95±0.86(P<0.05);HGF mRNA表达分别为-11.62±0.63、-10.56±0.48(P<0.05).结论 IFN-α对HGF及VEGF表达的抑制可能是其抗肿瘤血管生成作用、抑制肿瘤生长转移作用的机制之一.