建立适用于BALB/c Nude小鼠的急性肝衰竭模型

背景:在干细胞和组织工程领域的动物实验中,免疫缺陷裸小鼠(BALB/c Nude小鼠)对于提升研究准确性具有重要意义。但CCl致BALB/c Nude小鼠发生急性肝衰竭的浓度及检测时间尚不明确,严重影响该动物模型在具有免疫原性的干细胞治疗研究中的应用。目的:通过与C57小鼠急性肝衰竭模型比较,探索腹腔注射CCl建立BALB/c Nude小鼠急性肝衰竭模型的合适浓度和检测时间。方法:将50%浓度的CCl按照4 m L/kg腹腔注射到C57小鼠(n=6)和BALB/c Nude小鼠(n=6)体内,注射后72 h内观察小鼠存活情况。分别将50%,20%,10%浓度的CCl按照4 m L/kg腹腔注射到BALB/c Nude小鼠体内,注射后72 h观察小鼠存活情况,并进行肝脏病理切片形态学观察。根据建立两种小鼠急性肝衰竭模型的最佳CCl浓度,将50%浓度的CCl腹腔注射到C57小鼠体内,将20%浓度的CCl腹腔注射到BALB/c Nude小鼠体内,注射前后检测小鼠血清中谷丙转氨酶和谷草转氨酶水平。结果与结论:(1)CCl注射24 h后,C57小鼠的存活率为50%,BALB/c Nude小鼠全部死亡,提示现有针对C57小鼠的最适CCl浓度不适合BALB/c Nude小鼠造模;(2)注射50%浓度CCl的BALB/c Nude小鼠在24 h之内陆续死亡;注射体积分数20%CCl的小鼠24 h后存活率是66.7%,至注射后72 h存活率仍为66.7%;注射10%浓度CCl的小鼠至注射后72 h全部存活;注射后24 h肝病病理结果显示,CCl注射浓度越小肝脏损伤程度越轻,其中20%浓度的CCl最适合建立BALB/c Nude小鼠急性肝衰竭模型;(3)C57小鼠腹腔注射CCl4h后谷丙转氨酶和谷草转氨酶水平达到最高,1 d时开始下降;BALB/c Nude小鼠在腹腔注射CCl1 d后谷丙转氨酶和谷草转氨酶水平达到最高,3 d时开始下降;(4)结果表明,为提高动物实验可靠性,使用C57小鼠建立急性肝衰竭模型时应选择50%浓度的CCl,在注射后4 h施行干预措施;使用BALB/c Nude小鼠建立急性肝衰竭模型时应选择20%浓度的CCl,在注射后1 d施行干预措施。

在表现和设计的边缘跋涉——浅析马蒂斯Pink Nude创作中对形式要素的纯化

现代主义美术运动和现代设计艺术的起源密切相关。本文通过分析野兽主义画家马蒂斯油画作品Pinknude创作过程中画面形式发生的变化,探究艺术家从写实到抽象化,逐渐走向平面化和装饰性的内在动力,从而揭示艺术家作品与设计艺术的联系和根本区别。

Beige裸鼠(C57BL/6PB_1-beige/nude)的育成及其基本特性

作者依据位于非同源(non-syngenic)染色体上的两对非等位基因(non-allolicgene),在减数分裂时可以自由组合,并不融合,各自保持原有特性的细胞遗传学原理,采用培育同源系(Congenic strain)的杂交-互交系统(Cross-intercross system),将供体动物裸鼠的“nu”基因导入具有“bg”基因的受体动物Beige小鼠,通过两次回交七个繁殖步骤,在国内首次培育成功。

Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential

Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient like metastatic model of human HCC in nude mice (LCI-D20)and a Iow metastatic model of human HCC in nude mice LCI-D35 ) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding.Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-Iincreased gradually following tumor progression in LCID20 model, and correlated with tumor size and AFP level,Phasic expression of tissue intercellular adhesion molecule-I in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including antiangiogenesis, antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vivo and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.

Growth-inhibiting effects of taxol on human liver cancer in vitro and in nude mice

AIM To investigate the effects of taxol onSMMC-7721 human hepatoma and itsmechanisms.METHODS In vitro cell growth was assessedby trypan blue exclusion method.Experimentalhepatoma model was established by seedingSMMC-7721 cells subcutaneously into Balb/c(nu/nu)nude mice.In vivo tumor growth wasdetermined by measurement of tumor diameterwith Vernier calipers.The syntheses of DNA,RNA and protein were analyzed by incorporationof ~3H-thymidine,~3H-uridine and ~3H-leucinerespectively.Using light and electronmicroscopes to observe the morphologicalchanges of cells including mitosis andapoptosis.RESULTS Taxol was effective against SMMC-7721 human hepatoma cell growth in the rangesof 2.5 nmol/L-10 nmol/L with mitotic arrestand apoptosis in vitro.DNA,RNA and proteinsyntheses in cells were also obviouslysuppressed by in vitro treatment of taxol for72 h.Taxol at 2.5 nmol/L reduced ~3H-thymidineuptake to about 34% of the control value(P【0.05).Increasing the dose of taxol to20 nmol/L resulted in a greater decrease in ~3H-thymidine incorporation to 60% of the controlvalue(P【0.01).At a concentration of 20 nmol/L,the ~3H-uridine and ~3H-leucine uptakeswere reduced to 52%(P【0.05)and 63%(P【0.01),respectively.In vivo,taxolsignificantly inhibited SMMC-7721 tumor growthat 10 mg/kg,i.p.,once daily for 10 d.A morethan 90% decrease in tumor volume wasobserved by day 11(P【0.01)similarly withmitotic arrest and cell apoptosis.CONCLUSION Taxol has a marked anticanceractivity in SMMC-7721 human hepatoma both invitro and in nude mice.Its mechanisms might beassociated with mitotic arrest,subsequently,apoptosis of the hepatoma cells.No obvioustoxicity was observed with in vivoadministration of taxoi.

Effects of targeting magnetic drug nanoparticles on human cholangiocarcinoma xenografts in nude mice

BACKGROUND:Targeting is a new therapeutic tool for malignant tumor as a result of combining nanotechnology with chemotherapeutics.The aim of our study was to investigate the effects of magnetic nanoparticles enveloping a chemotherapeutic drug on human cholangiocarcinoma xenografts in nude mice. METHODS:The human cholangiocarcinoma xenograft model was established in nude mice with the QBC939 cell line.The nude mice were randomly assigned to 7 groups. 0.9%saline or magnetic nanoparticles,including high (group 2),medium(group 4)and low(group 5)dosages, were given to nude mice through the tail vein 20 days after the QBC939 cell line was implanted.Calculations were made 35 days after treatment in order to compare the volumes,inhibition ratios and growth curves of the tumors in each group.Mice in each group were sacrificed randomly to collect tumor tissues and other organs for electron microscopy and pathological examination. RESULTS:The high and medium dosage groups were significantly different from the control group(P【0.05). The tumor inhibition ratios for the high,medium and low dosage groups were 39.6%,14.6%and 7.9%,respectively. The tumor growth curve of groups 5,4,and 2 changed slowly in turn.The high and medium groups showed cell apoptosis under an electron microscope.CONCLUSION:Magnetic nanoparticles can inhibit the growth of human cholangiocarcinoma xenografts in nude mice.

^(99m)Tc-labeled HAb18 McAb Fab fragment for radioimmunoimaging in nude mice bearing human hepatocellular carcinoma

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Phase tissue intercellular adhesion molecule-1 expression in nude mice human liver cancer metastasis model

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Study of primary leiomyosarcoma induced by MNNG in BALB/C nude mice

INTRODUCTIONIt has been well known that MNNG is one of thestrong and multipotential carcinogens that havebeen frequently reported inducing malignant peptictumors.We have successfully induced rat and doggastric adenocarcinomas,squamous cell carcinomasof rat forestomach and gastric leiomyosarcoma

Beige-Nude小鼠免疫学特性研究概况

免疫缺陷动物是研究免疫相关疾病的良好动物模型。Beige-Nude小鼠是T淋巴细胞和NK细胞同时缺陷的小鼠,其T细胞和NK细胞活性很低,最初为肿瘤的研究而培育。从上世纪七十年代起,学者们对其免疫学特性进行了广泛而深入的研究,为其在其他领域的应用奠定了免疫学基础。

Tumor radioimmunoimaging of chimeric antibody in nude mice with hepatoma xenograft

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Systemic study on the safety of immuno-deficient nude mice treated by atmospheric plasma-activated water

Cold atmospheric-pressure plasma is a new technology, widely used in many fields of biomedicine,especially in cancer treatment. Cold plasma can selectively kill a variety of tumor cells, and its biological safety in clinical trials is also very important. In many cases, the patient's immune level is relatively low, so we first studied the safety assessment of plasma treatment in an immunocompromised animal model. In this study, we examined the safety of immuno-deficient nude mice by oral lavage treatment of plasma-activated water, and studied the growth status, main organs and blood biochemical indexes. Acute toxicity test results showed that the maximum dose of plasma treatment for 15 min had no lethal effect and other acute toxicity. There were no significant changes in body weight and survival status of mice after 2 min and 4 min of plasma-activated water(PAW)treatment for 2 weeks. After treatment, the major organs, including heart, liver, spleen, lung and kidney, were not significantly changed in organ coefficient and tissue structure. Blood biochemical markers showed that blood neutrophils and mononuclear cells were slightly increased, and the others remained unchanged. Liver function, renal function, electrolytes, glucose metabolism and lipid metabolism were not affected by different doses of PAW treatment. The above results indicate that PAW treatment can be used to treat immuno-deficient nude mice without significant safety problems.

Gene therapy with antisense c-myc adenovirus for human gastric carcino-ma cell line in vitro and for implanted carcinoma in nude mice

Objective:To study the effects of recombinant antisense c-myc adenovirus (rAS-c-myc-Ad) on SGG 7901 human gastric carcinoma cell line in for and in nude mice. Methods:The effects of rAS-c-myc-Ad and LacZ-Ad on SGG 7901 gastric carcinoma cells were observed with X-galstaining, MTT, DNA gradient degradation test, TUNEL, flow cytometry, PCR and western blot. The therapeutic effects of rAS-c-myc-Ad on the implanted ax 7901 cells in nude mice were also ob served.Results: rAS-c-myc-Ad significantly inhibited the growth of SGG 7901 cells and induced their apoptosis. After the treatment of rAS-c-myc-Ad, the prolifetion rate of the cells was decreased by 44’ l% in de and SGC 7901 cells failed to form caxcinoma ther they were implanted into nude mice. Injection of rAS-c-myc-Ad into the carcinoma subcutaneously implanted to the nude mice significantly inhibited the growth of the implanted carcinoma with an inhibition rate of 68. 9%. Conclusion: rAS-c- myc- Ad significantly inhibits the growth of SGG 7901 human gastric carcinoma cells in vitro and in nude

INVESTIGATION OF TUMORIGENIC EFFECT ON ULTRAWEAK LUMINESCENCE FROM NUDE MOUSE FOR ANIMAL MODEL

With nude mouse for animal model, this paper has investigated its whole body luminescence after or before it was inoculated with tumor, and the relationship between tumorigenesis and the luminescence, then, studied the luminescence difference from different mouse organs and find out sensitive luminescence organs. Furthermore, it has tested possibie luminescence mechanism with beta- carotene, NaN3 and D2O. This paper is supposed to provide a new feasible method for cancer diagnosis.

INHIBITORY EFFECT OF DEMO ON THE GROWTH OF TRANSPLANTED HUMAN COLON CANCER IN NUDE MICE

A human colon cancer cell line Hce- 8693 was heterotransplanted in nude mice. Polyamine blosythesis Inhibitor a- dlfiuoromethylomithine (DFMO ) show a marked reproducible inhibition in this model. The size and weight of transplanted tumor In DFMO group were smaller than those of the control group and the average inhibition rate was 72.8% (P 【 0.001) . DFMO showed higher tumor inhibitory rate than 5-Fu (35. 4%) (P【0. 001) . Furthermore. DFMO demonstrated less severe bone marrow inhibition in the nude mice than 5-Fu (20. 0% Vs 53. 2%. P【0. 001) .There was no synergistic action in these two drugs at the experimental dose. The concentration of putrescine and spermidine in the plasma and tumor tissue in the DFMO group were 70% lower than those of the control group (P【0. 001) . These results indicate that the anti-tumor effect of DFMO might be explained by the inhibition of polyamine biosynthesis and this study provides an experimental basis for future clinical application of DFMO.

RESEARCHES ON THE ANTI-AUTOLOGOUS TUMOR EFFECTS OF HUMAN CANCER-KILLING CELLS IN NUDE MICE

An investigation of human splenic LAK cells killing autologous tumor in vivo has been performed in this study. Briefly, an ovary embryo carcinoma (OEC) removed surgically from patient was transplanted Into nude mice (s. c. ) and cultured in vitro, that would be used as targets. Lymphokine-activated killer (LAK) cells were generated from splenic lymphocytes of the OEC patient, who died two and half months after operation, by co- culture with recombinant human interleukin- 2 ( rIL- 2 ) in vitro. The results from Winn’ s test in nude mice suggested that these LAK cells could effectively inhibit the tumorlgenicity of autologous tumor m vitro.

Radioimmunodetection of human choriocarcinoma xenograft in nude mouse

Objective: To study the efficiency of radioimmuno-detection in locating the xenograft of human chorio-carcinoma in nude mouse. Methods: Radioimmuno-detection was performed using cocktail antibodies of 131I-labeled mouse anti-human chorionic gonadotropin monoclonal antibodies to locate the xenograft of human choriocarcinoma in nude mouse. Radioactivity in different tissues was measured and the tumor/non-tumor ratio was calculated. Normal mouse IgG was used as control IgG. Results: The accumulation of radioactivity in the xenograft area could be recognized as early as 24 h after the injection of the radiolabelled antibodies. 72-96 h after the injection, the xenograft could be clearly shown. The minimal shown xenograft was 0.8 cm in diameter. The tumor/non-tumor ratio increased with the time and was obviously higher than that in control group. Conclusion: Radioimmunodetection can efficiently locate human choriocarcinoma xenograft in nude mouse.

Intravesical Instillation in Pure Line LEW Rats and Nude Mice

In order to study bladder intravesical instillation methods in pure line LEW rats and nude mice, female LEW rats and nude mice aged 2 to 4 weeks were sacrificed. Their urethra and bladder were observed under anatomical microscopy. A trochar was prepared according to the outline and an- gle of the urethra. Ink was poured into female rats and nude mice bladder though urethra. Filling and staining of bladder were observed and evaluated under anatomical microscopy. Status and urethral injury of rats and mice were observed. The results showed that urethra anatomic structure of rats and nude mice was different from that of human urethra. When bladder was filled with ink and became blue, liquid was not seen to leak out. The success rate of intubation was high (100%). Living activi- ties of animals weren’t influenced by intravesical instillation. It was concluded that bladder irrigation might be a kind of valid and utilizable method in pure line rat and nude mouse empirical study. The model may be a more effective tool for study of bladder tumor.

Histological analysis of human pancreatic carcinoma following irreversible electroporation in a nude mouse model

AIM To determine changes in the morphology and function of pancreatic cancer cells after irreversible electroporation(IRE) treatment, and to explore the clinical significance of IRE treatment for pancreatic cancer providing an experimental basis for the clinical application of IRE treatment. METHODS IRE was carried out in an athymic nude mouse model of pancreatic carcinoma generated with human pancreatic cancer cells 1. In therapy groups, IRE electrodes were inserted with 90 pulses per second at 800 V/cm applied to ablate the targeted tumor tissues. Histological assessment of the affected tissue was performed by hematoxylin and eosin staining(HE). Quantification of cell proliferation and apoptosis was performed by evaluating Ki67 and caspase-3 levels, respectively. Flow cytometry was used to assess cell apoptosis. Ultrasound imaging was carried out to evaluate IRE treatment results. Pathological correlation studies showed IRE is effective for the targeted ablation of pancreatic tumors in an orthotopic mouse model.RESULTS IRE was efficacious in removing tumors in the orthotopic mouse model. The IRE-ablated zone displays characteristics of nude mouse models at different time-points as assessed by hematoxylin and eosin staining. Immunohistochemical analysis of samples from the pancreatic cancer models showed significantly enhanced caspase-3 cleavage and Ki67. Flow cytometry data corroborated the above findings that apoptosis in tumor cells was observed immediately on the first postoperative day, and with time the middle and late stages of apoptosis were observed. For ultrasound imaging studies, the IRE ablation zone became a hyperechoic area due to increasing inflammatory and immunologic cellular contents. CONCLUSION IRE is a promising new approach for pancreatic cancer, with many potential advantages over conventional ablation techniques.