A STANDARDIZED METHOD OF USING NUDE-MICE FOR THE INVIVO SCREENING OF ANTITUMOR DRUGS FOR HUMAN TUMORS

Human tumors transplanted into nude mice have long been used to assess the effectiveness of antitumor drugs and yet there is still no establ ished standard method in pre-clinical practice for screening new antit umor drugs in vivo using nude mice. Thus, a cooperative study on the f easibility of a human tumor/nude mouse system for the in vivo screenin g of drugs was conducted by the Japanese Research Society for Chemosen sitivity of Cancer. Two human stomach cancers, H-111 and SC-6-JCK, and one human colon cancer, Co-4, were transplanted serially into nude mi ce and used as gastrointestinal tract tumors with stable tumor growth. The appropriate dosage of six well-known antitumor drugs [mitomycin C (MMC), cyclophosphamide (CPA), nimustine hydrochloride 1-(4-amino-2-m ethyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochlor ide (ACNU), cisplatinum (II) diaminodichloride (CDDP), adriamycin (ADM ) and 5-fluorouracil (5-FU)] in human tumor-bearing nude mice was dete rmined based on the maximum tolerance dose of the drug. The respective dosages were 6 mg/kg of MMC x 1 (i.p.), 120 mg/kg of CPA x 1 (i.p.), 30 mg/kg of ACNU x 1 (i.p.), 8 mg/kg of CDDP x 1 (i.p.), 8 mg/kg of AD M x 1 (i.v.), and 50 mg/kg of 5-FU q4d x 3 (i.p.). Three weeks after t reatment, drug effectiveness was judged by the tumor growth inhibition rate. Treatment with these appropriate doses appeared to show the max imum effect of the respective drugs on the tumor-bearing nude mice. Th is standardized method using nude mice should contribute to the screen ing of new antitumor drugs against human tumors, especially those of t he gastrointestinal tract. The antitumor activity of new drugs on huma n tumors in vivo may now he determined by comparison with that of well -known antitumor drugs on human tumor-bearing nude mice.