Validating of the pre-clinical mouse model for metastatic breast cancer to the mandible

Metastatic breast carcinoma has a great tendency to spread to the mandible. It is concomitantly associated with bone destruction, food intake disorder, and a poorer prognosis. Appropriate animal models need to be developed for a better understanding of the mechanisms underlying the metastatic process of breast cancer cells to mandible and to test the effects of potential lead compounds. Here, we assessed the metastasis model of intracardiac injection using luciferase-transfected metastatic breast cancer cells (MDA-MB-231^Luc+) by determining the incidences of metastasis, mCT images, and histopathological results. A high bioluminescence signal mainly detected mandibular lesions with less frequent distal femora and proximal tibiae lesions. Extensive mandibular bone destruction occurred in nude mice grafted with metastatic breast cancer cells. This type of animal model might be a useful tool in assessing therapeutic implications and the efficacy of anti-cancer drugs for osteolytic cancers.     

基于组织块法建立的移植瘤模型在肿瘤方面的研究进展

基于组织块法建立的移植瘤（PDTX）模型就是取患者的癌组织在免疫缺陷鼠体内增殖传代,培养出的肿瘤组织不仅保留了亲代肿瘤的生物学特征、染色体特征、肿瘤标志物等,还保留了亲代肿瘤的组织结构特征,更大程度的模拟人体内环境.此模型可用于评价抗肿瘤药物的疗效、探索抗肿瘤药物的耐药机制、分析生物标志物等,从而为患者提供个体化治疗方案.     

Stability of preclinical models of aggressive renal cell carcinomas

Renal-cell carcinomas (RCC) are often resistant to conventional cytotoxic agents. Xenograft models are used for in vivo preclinical studies and drug development. The validity of these studies is highly dependent on the phenotypic and genotypic stability of the models. Here we assessed the stability of six aggressive human RCC xenografted in nude/NMRI mice. We compared the initial samples (P0), first (P1) and fifth (P5) passages for the following criteria: histopathology, immunohistochemistry for CK7, CD10, vimentin and p53, DNA allelic profiles using 10 microsatellites and CGH-array. Next we evaluated the response to sunitinib in primary RCC and corresponding xenografted RCC. We observed a good overall stability between primary RCC and corresponding xenografted RCC at P1 and P5 regarding histopathology and immunohistochemistry except for cytokeratin 7 (one case) and p53 (one case) expression. Out of 44 groups with fully available microsatellite data (at P0, P1 and P5), 66% (29 groups) showed no difference from P0 to P5 while 34% (15 groups) showed new or lost alleles. Using CGH-array, overall genomic alterations at P5 were not different from those of initial RCC. The xenografted RCC had identical response to sunitinib therapy compared to the initial human RCC from which they derive. These xenograft models of aggressive human RCC are clinically relevant, showing a good histological and molecular stability and are suitable for studies of basic biology and response to therapy.     

玉屏风颗粒抑制鼻咽癌作用实验研究

目的 探讨玉屏风颗粒对鼻咽癌的治疗作用。方法 采用人鼻咽癌CNE-2细胞模型和裸鼠体内异种移植瘤模型,研究玉屏风颗粒对CNE-2细胞存活率和荷鼻咽癌裸鼠肿瘤体积、体重及生存期的影响。结果 玉屏风颗粒对CNE-2细胞有明显的抑制作用。与对照组相比,玉屏风颗粒组[4 g·(kg·d)^-1]能显著增加荷鼻咽癌裸鼠体重,并抑制肿瘤的生长;顺铂组（每周6 mg·kg^-1）及玉屏风颗粒+顺铂组[4 g·(kg·d)^-1+每周6 mg·kg^-1]则显著降低荷鼻咽癌裸鼠体重,并抑制肿瘤的生长。玉屏风颗粒单独使用和与顺铂联用均能显著延长裸鼠的生存期。结论 玉屏风颗粒具有抑制鼻咽癌作用,能显著延长荷鼻咽癌裸鼠生存期,提高生存质量,未发现明显毒副作用。     

Humanized NOD-SCID IL2rg mice as a preclinical model for cancer research and its potential use for individualized cancer therapies

Humanized mouse models have been developed and utilized in cancer research for decades. Newly developed combined immunodeficient NOD-SCID-IL2rg^–/– mice are more permissive for human cells and tissue engraftment. In this review, we discuss the use of NOD-SCID-IL2rg^–/– mice as a preclinical tool in cancer research and its potential use for individualized cancer therapies.     

绿色荧光蛋白标记的鼻咽癌放射抗拒性裸鼠移植瘤模型的建立及其活体成像观察

目的建立绿色荧光蛋白（greenfluorescentprotein,GFP）标记的鼻咽癌放射抗拒性裸鼠移植瘤模型,为后续研究奠定基础。方法将以慢病毒转染的方法建立稳定表达GFP标记的人鼻咽低分化鳞癌细胞株GFP．CNE-2和放射抗拒性细胞株GFP—CNE-2R接种至裸鼠体内,建立皮下移植的肿瘤模型。待肿瘤直径约为1em时给予相同剂量10Gv的X射线一次性照射,通过小动物活体成像仪观察移植瘤的生长和转移情况。结果成功建立了稳定表达GFP标记的放射抗拒性及放射敏感的人鼻咽低分化鳞癌细胞株GFP—CNE-2R和GFP—CNE．2。克隆形成实验显示GFP—CNE．2R细胞株具有放射抗拒性。GFP—CNE-2R和GFP—CNE-2细胞的皮下成瘤率均为100％,证实建模成功。相对于GFP—CNE．2裸鼠移植瘤,GFP—CNE-2R移植瘤的生长受照射抑制不明显。结论相对于GFP—CNE-2裸鼠移植瘤,GFP-CNE-2R裸鼠移植瘤具有更强的放射抗拒性。     

Histologic evaluation of human cadaveric fascia lata in a rabbit vagina model

The purpose of this study was to evaluate the histologic response of human cadaveric fascia lata after vaginal implantation. Freeze-dried, gamma-irradiated cadaveric fascia lata from three lots was implanted between the rectovaginal membrane and vaginal epithelium in New Zealand white rabbits. Rabbits were killed at 2, 4, 8, and 12 weeks after implantation. At necropsy, gross findings were described and specimens for routine cultures were taken. Histologic evaluation determined graft integrity, neovascularization, inflammatory response, and host tissue incorporation. Nine rabbits were available for histologic analysis and 14 for gross and microbiologic analysis. Vaginal erosions occurred with three grafts. The remainder were adherent to the surrounding tissues. Erosion was associated with bacterial colonization of the graft. Autolysis of one graft occurred at 4 weeks. Over time, the inflammatory response decreased and neovascularization increased; by 12 weeks, the graft collagen was replaced by host collagen. Cadaveric fascia lata serves as scaffolding for host tissue incorporation with replacement by host collagen.Oral/Poster presentation at the Annual Meeting of the Society of Gynecologic Surgeons, Orlando, Florida, March 2001.     

单核细胞、NK细胞和T细胞在猪-猕猴延迟性异种移植排斥反应中的作用

目的观察单核细胞、NK细胞和T细胞在猪-猕猴延迟性异种移植排斥反应(DXR)中的作用。方法建立湖北白猪-云南猕猴的腹腔异位心脏移植模型，实验分为2组：对照组(n=5)，不使用中华眼睛蛇毒因(Y-CVF)；实验组(n=4)应用Y-CVF完全清除受者体内补体。2组受体猴均采用环孢素A(CsA)，环磷酰胺(CTX)和甲基强的松龙(MP)三联免疫抑制治疗。免疫组织化学方法检测移植心组织中细胞间黏附分子(ICAM)-1、肿瘤坏死因子(TNF)-α、单核细胞、NK细胞和T细胞的表达。结果对照组3个移植心在15～60min内发生超急性排斥反应(HAR)，另2个分别存活22h及6d，移植心均未见明显的炎性细胞浸润及ICAM-1和TNF-α的表达。实验组移植心存活时间分别为8、10、13和13d，移植物浸润细胞中可见大量的单核细胞(50％)，少量的NK细胞(8％～10％)，CD4^ T细胞(15％)和C08^ T细胞(25％)。移植物血管内皮细胞表面出现ICAM-1的表达上调，移植物间质中出现TNF-α的表达增加。结论单核细胞、NK细胞和T细胞介导的移植物损伤，在应用Y-CVF处理的猪-猕猴DXR发生中发挥重要作用。     

复合基因重组人骨形成蛋白-2异种骨的研制及成骨活性研究

目的　研制新型具有诱导成骨活性的异种骨植骨材料。方法　在重组合异种骨 (RBX)基础上 ,以基因重组人骨形成蛋白 - 2 (rh BMP- 2 )取代从牛皮质骨中提取的牛 BMP,与去抗原牛松质骨载体 (BCB)复合 ,制成复合 rh BMP- 2的异种骨 (rh BMP- 2 / BCB) ;将 4周龄雄性 BAL B/ C小鼠 6 0只 ,随机分为实验组和对照组 ,于实验组小鼠左股部肌袋植入 rh BMP- 2 / BCB骨粒 ,对照组小鼠左股部肌袋植入 BCB骨粒 ,术后 7、14及 2 1天取材 ,通过组织学、骨计量学方法检测 rh BMP- 2 / BCB的诱导成骨活性。结果　 1实验组术后 7天在小鼠肌袋可诱导软骨生成 ,14天形成编织骨 ,2 1天改建成板层骨并形成大量骨髓 ;对照组于术后各时间点均未见有软骨及骨形成。 2实验组的碱性磷酸酶活性和钙含量均高于对照组 ,具有统计学意义 (P<0 .0 1)。结论　 rh BMP- 2 / BCB具有较好的骨诱导能力 ,是一种较理想的植骨材料     

氢质子磁共振频谱活体检测结肠癌耐药性的初步探讨

目的 探索1H-MRS活体检测结肠癌耐药性的可能性。方法 5只耐药(耐5-FU)与5只不耐药人类结肠癌SW480荷瘤裸鼠于肿瘤直径大于1.5cm时行1H-MRS检查,随后处死荷瘤鼠,切下肿瘤检测其PKC、P-gp、MRP1蛋白表达(Western Blot),观察肿瘤凋亡(TUNNEL法)。分析结肠癌耐药性与1H-MRS检测代谢物、肿瘤耐药基因表达、肿瘤凋亡的相关性。结果不耐药组人类结肠癌SW480裸鼠肿瘤的cho、lac、Lip及m I峰/cr面积比较耐药组人类结肠癌SW480/5-FU裸鼠增加,差别有统计学差异(P0.05)。耐药组PKC、P-gp、MRP1蛋白表达明显高于不耐药组,差别有统计学差异(P0.05)。在TUNNEL检测切片上,两组肿瘤组织均可见肿瘤细胞凋亡,两者差别无统计意义(P0.05)。肿瘤代谢物cho、Lac、Lip、m I/cr与肿瘤耐药性呈正相关性;cho面积与肿瘤PKC表达光密度呈正相关,与肿瘤Pgp表达光密度呈正相关。结论 肿瘤代谢物cho、lac、Lip的改变有可能有助于利用1H-MRS活体检测结肠癌耐药性改变。