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1、肿瘤模型专题1.最新的药效学指导原则要求化药临床前进行至少5 种人源肿瘤的体内抗癌活性评价，以确定药效及抗瘤谱。2.瘤株对药物的敏感性通过体外筛选可以说明，而体内评价更大程度上是考虑药物经体内吸收、分布、代谢之后的活性，由于目前的肿瘤模型多采用皮下接种，并不能完全反映药物的组织分布对其影响，所以感觉这种要求就显得不是很必要。注解：体内的敏感性不是仅考虑吸收分布代谢的影响，一些样品，体外活性都是不错的，体内甚至是瘤内直接注射给到很高剂量都没有效果，肿瘤细胞在体内和体外的生存环境差别很大，体外模拟的生存环境完全不能体现出体内的状态。3.皮下接种是一个目前能找到的最好的权宜之计了，实际上，SFDA明
2、确表示，鼓励原位肿瘤模型，但是由于技术的原因，很多瘤株都无法实现。而皮下模型有它的一系列优点：稳定，便于观察，易于构建，易于控制等等，能够在一定程度上反映药物经过体内过程的疗效，所以目前只能用它来进行评价。4.实际上原位肿瘤模型仍然不能很好的反映临床肿瘤的特点，目前能够预见得到最好的模型应该是经过基因修饰（转基因等）的能够集中比较均匀的自发模型，这才是和临床最接近的肿瘤模型。但是目前的经过基因修饰的自发肿瘤模型种类很少，而且可控制性差，周期长，所以还要经过很长时间的改善才能大规模的应用。5.常规的肿瘤细胞株接种后如果不能成瘤，细胞悬液就会被动物吸收6.瘤体积可用游标卡尺量最长径（a)和最短径（
3、b），体积计算公式：V=ab2/6,每 2-3 天测一次。体积=宽2*长/2 的公式计算肿瘤体积；抑瘤率=（对照组-治疗组）/对照组*100%；tumor size=width2 length 0.52).；ab2/6；关于肿瘤体积的计算：3.1415926./6约等于/2。如果想做得讲究一点，应该用RTV计算肿瘤体积：RTV（某日某老鼠的相对肿瘤体积）=TV(测量当天该老鼠的肿瘤体积）/TV（分组当天该老鼠的肿瘤体积）*100，在此基础上进行平均值SD等数据的计算7.是否必须称重小鼠的胸腺和脾脏8.超过 7 天的腹水再传代就很容易出现血性；动物的周龄也不要太大，6 周左右。传代次数太多也很容
4、易出现血性腹水。血性腹水可以离心后加 0.17 N 的 NH4CL 溶液破红细胞，然后精确一些的控制条件（接种量，传代时间，动物周龄等）传几代，很多情况下再传一两代后会有不血性的种鼠出现，然后用这只种鼠的腹水继续传代9.皮下接种与剥瘤子：小鼠肿瘤剥瘤子是一个艰难的过程，但是可以一定程度上的改善一下：接种的时候要精确控制接种在皮下，靠皮内会与皮肤强烈粘连，靠肌肉会与肌肉强烈粘连，而且不要文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR1
5、0F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR
6、10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 H
7、R10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3
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9、 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G
10、3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1
11、G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10太靠腋窝里面，可以往尾部靠一些，也可以稍微的往背部靠一点，不要往腹部靠，容易使肿瘤被垫料磨烂。10.LD50 是毒理中的半数致死量，ED50 是体外试验中的半数有效量，一般体内实验没有类似的指标，如果想比较几个类似物的药效还是做量效曲线比较好。11.剂量设置应该按照LD10(10%致
12、死剂量，也叫最大耐受剂量）来分组，一般分别采用1/2 LD10,1/4 LD10,1/7 LD10 或 1/10 LD,但最大剂量不得超过LD10。这里面还得考虑 ED 50，LD10 与 ED50的剂量相差越大越好。用 LD50 作为标准设置剂量是不现实的，因为动物实验是不可能允许10%以上动物死亡的。12.说到疗效的比较，如只是发文章，比较不同基团之间可能对母体抑瘤率的影响，一般做做体外试验，比一比大家的IC50 就好了，不太做体内。如是真正的筛药，我个人有些观点：这个不是孤立起来看某个或者某几个剂量下谁比谁的抑瘤率高。主要要看谁更具有可开发性。首先，要考虑它的毒性以及治疗窗口 的大小，通
13、俗的说，就是这个要在发挥疗效的剂量下，毒性是否大？比如A药，10mg 抑瘤率有 50%，但是体重下降了20%;而 B药，10mg的时候根本无效，30mg 的时候有 40%的抑瘤率，60mg 的时候抑瘤率高达 80%，而且体重几乎没有下降，这个时候 A 药与 B 药如何比较？特别如果是公司筛选新药，还要考虑成本，病人可接受度（动物上的有效剂量换算到人一天要吃2 斤，这种药也是不现实的），制剂，工艺等等方面。如果单纯从药理的角度给出答案，文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1
14、G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S
15、1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1
16、S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K
17、1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2
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19、2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 Z
20、R2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10至少要考虑 毒性和剂量限制 的问题。13.关于剂量选择，LD50 的几分之一是一种比较通用的方法，目前相对更合理一些的剂量选择是做一个简单的多次给药的毒理试验来确定剂量，我们一般会连续给药一周，然后再观察一周，这样摸出来的最大剂量可以
21、直接用于药效试验，然后其他的剂量都在此剂量的基础上往下减。14.说到给药疗程，一般初筛的药物都是连续天天给药，qd。但是给药途径，特别是i.v 与 i.p 的选择，我们都是先做一个简单的PK试验考察一下，再确定，特别是如果PK 试验的结果显示，血药浓度甚至达不到体外IC50 的浓度，那么是否进行体内试验，就有待商榷了。连续 i.p，小鼠的皮肤有时候会变厚，你可以换一边给药。15.动物选择:KM 小鼠,裸鼠,C57 等均可作为,但是个人认为 KM 能做出来最好,毕竟比较有普遍性,还是正常生理状态的健康动物,比较有说服力,还便宜,裸鼠或者其他特定品种,比较适合特定的瘤株16.关于肿瘤细胞活力的问题
22、:一般培养的肿瘤细胞活力往往是不够的,很难在短时间内长到规定重量,所以建议至少在动物体内传2代,让肿瘤细胞活力充分体现以后再开始用于实验.传代数次的原因在于让肿瘤细胞充分活化，要不活化也行，多接种点吧17.关于接种部位的问题:以小鼠为例一般可以选择腋下或者后肢,背部血管不发达,营养不够,一般不建议采用.接种一般采用皮下注射,针头沿皮肤水平进入,然后挑起表皮,注射文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 Z
23、R2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4
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25、 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A
26、4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4
27、A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L
28、4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10
29、L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K1018.关于肿瘤重量的问题:模型组肿瘤重量应该不低于0.5g19.肺内原位注射制作肿瘤模型效果颇好,流程如下:麻醉-固定-皮肤消毒-剪开左侧胸部皮肤,大约第 2-3 肋间的位置-用镊子轻轻拨开皮下筋膜,可以看到呼吸运动的肺叶-将准备好的肿瘤细胞注射入肺,分层缝合 OK20.胸膜活检穿刺针规格：#20#25(1
30、4G 12G)L 65 mm；用途：供人体胸腔穿刺，钩取胸膜活体组织用21.开始做肿瘤药效评价，应该采用 s180 这些小鼠肿瘤模型。一个方面这些肿瘤对于药物很敏感，而且周期短，花费也少。但如果要成药，裸鼠模型是必需的。22.一般瘤重的 SD 在平均值的 7080%以下就还凑活，漂亮一点的是在 30%以下，实在不行，100%也勉强，就是特别难看，但是SD越大，统计上就越不利23.皮下肿瘤模型中，腋下最适合肿瘤生长。接种时由裸鼠体侧腰部稍靠上的部位进针，要保证与接种点的距离小于针头的长度，向头部方穿行，绝对不能刺破皮肤或者刺破肌肉层，当针头到达接种位点时注射，退出针头，这样操作的目的并不完全是避
31、免漏液，其实熟练后，不需要皮下穿行也不会漏液，主要是避免污染，进针点还有少量污染的可能性的，针头在皮下穿行一段后，接种点离进针点较远，最大限度减少污染的可能。24.如果是药效试验，不建议你用手术标本，因为SFDA 的临床前研究指导原则上明确指出要用建株的肿瘤株进行试验，因为用手术文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4
32、ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4
33、 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A
34、4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4
35、A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L
36、4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10
37、L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H1
38、0L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10标本的试验可重复性太差25.一般用 4-5WK，体重 1517g 鼠，年轻鼠接种瘤容易长26.种植肾被膜下：第一该区免疫豁免，第二贴近肾可以从此获得充分的养料.在实验时先用显微用的镊子在肾被膜上撕慨一个小口子,然后种植。注意:肾被膜和肾脏是有一个间隙可以用镊子在被膜下赶肿瘤组织到远离撕开口处,不用缝合被膜.这样就可以了27.人肿瘤模型用裸鼠，基本上没有可成腹水的，只能皮下接种传代28.nu
39、de mice 的数据在 SCID mice 上是比较有参考价值的，另外，因为免疫系统的进一步缺乏，肿瘤生长的进程可能会比nude mice上更快一点29.接种后，用干净的棉签按住注射部位才拔针,拔针后再按住 10 秒种左右,一般不会有液体渗出30.K562 第一代细胞接种的成瘤很好，传一代就很差了，没有几只成瘤的，到第三代就全军覆没31.不赞同用 7901 这个瘤株，国际公认度比较差32.分组要求平行性，尽量缩小组间差异，组内差异是实际情况的反映。你可以按照肿瘤体积分层随机分组，这样平行性比较好33.肿瘤细胞悬液裸鼠接种前稀释效果顺序：相应的无血清培养基PBSsaline34.现在常用的阳性
40、对照药物是CTX和 cisplatin，另外乳腺癌可以用Taxol。阳性药的剂量途径和疗程不要求和样品一致，不过给药途径尽量一样。还有，最好选用机制类似或者结构类似的阳性对照。文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9
41、K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G
42、9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1
43、G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S
44、1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1
45、S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K
46、1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2
47、K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10一般来说阳性对照的抑制率都会在60%以上或者更大，少数情况下只有 50%左右。35.细胞毒类抗肿瘤药物临床前体内试验一般至少应选用6 种人癌移植瘤模型，其中应包括II 期临床试验中拟筛选的肿瘤组织类型。36.针对每一种人癌移植瘤模型，推荐采用相对肿瘤增殖率T/C（%）作为试验评价指标，评价标准通常为：T/C（%）40%为无效；T/C（%）40%，并经统计学处理P 0.05 为有效。在体内有效性试验采用的全部人癌移植模型中，一般至少应有1/3 达到有效标准。注解：对于 T/C40%，按照这个标
48、准，很多现有的一线化疗药物都会被淘汰37.适于接种的瘤源的直径最好为1cm 或者稍大一点，直径2cm 可能对于有些瘤株来说会太大了一点。一般来说，插块法，一个瘤源接种 30 只动物是没有问题的，匀浆法一般2 只也可以接种 30只了38.新的抗肿瘤药物指导原则上强调要3 代以上才能用，并且不能超过 1520 代（人肿瘤）。39.只有少部分的小鼠实体瘤可以腹水传代，人实体瘤几乎没有能够腹水传代的40.一般来说，小鼠肿瘤比较推荐路易斯肺癌和B16。国内的S180并不好，各实验室之间的变异很大。国外基本都不用它。其实并不是因为 S180 有多好大家才选用他，而是他进行实验的成本低，周期短，操作较容易文
49、档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10
50、文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K10文档编码:CJ4H7A9P1G3 HR10F7H10L4A4 ZR2K1S1G9K1