A reversed-phase HPLC method for determination of isotetrandrine (ITD) in biological specimens was developed. The mobile phase composed of 0.2% (w/v) SDS, 47% acetonitrile and 53% distilled water (pH 2), at a flow rate of 1.5 ml/min with determination wavelength of 230 nm. The drug concentration-time curves of ITD in rats after iv of 12.5, 25 and 50 mg/kg were shown to fit a two-compartment open model with half-lives of 67.1 +/- 6.22 68.0 +/- 2.57 and 97.6 +/- 14.6 min, respectively. At doses of 12.5 and 25 mg/kg, the elimination of the drug from plasma was found to be in accord with linear kinetics, but when the dosage was 50 mg/kg, a non-linear kinetics was observed. Following ig ITD 100 and 250 mg/kg, the plasma concentration-time curves exhibited two marked peaks. Half-lives of elimination after ig doses was much longer than after iv administration, with mean values of 9.35 +/- 3.24 h (100 mg/kg) and 9.01 +/- 3.02 h (250 mg/kg). Distribution of the drug in rats was extensive, highest level of the drug was found in the lung and lowest in plasma after iv administration. Following ig administration, highest level of the drug was found in the liver and lowest in plasma.

DNA topoisomerase I has been isolated from the nuclei of calf thymus by PEG fractionation and chromatography on P11 and on Bio-Rex 70. Either a positive or negative supercoiled pBR322 DNA can be relaxed by the enzyme. The activity of Topo I is Mg2+ and ATP independent. Some of nonintercalative antitumor drugs such as camptothecine, hydroxycamptothecine, cyclophosphamide, methotrexate and mitomycin C were found to inhibit the activity of Topo I. The results suggest that DNA Topo I can be used to screen new nonintercalative antitumor drugs as a target protein.

From Jan. 1985 to Dec. 1988, 100 newborn and small infants suffering from lymphangioma were treated with bleomycin A5 injecting into lymphangioma. The cases were divided into three types: (1) Bleomycin A5 local injection into the lymphangioma were practiced on 70 cases; (2) Surgical partial resection of lymphangioma plus local injection on 26 cases; (3) A previous excision but recurred postoperatively were 4 cases. The dosage of bleomycin A5 was 10 mg per time. The therapeutic course was not more than 5 times. The efficacy of bleomycin A5 were satisfactory in all cases except only one case with a large lymphangioma of previous palliative excision but recurred. There was not a recurrent patient at following-up from 3 months to 4 years.

Bimolane (AT-1727), 1,2-bis (4-morpholinomethyl-3,5-dioxopiperazinyl)-ethane, is a new antitumor drug, synthesized first in our institute. When the mice were injected ip bimolane 3.7 or 37.2 mg/kg on d 6-15 after mated, 23 or 100% of the embryos were resorbed, while the surviving fetuses remained normal. After ip bimolane 7.4 or 14.9 mg/kg, the weights of living fetuses were all less than that of the control group (P less than 0.01). After ig bimolane 140 mg/kg to the mice on d 6-15 after mated, 43% of the fetuses developed subcutaneous edema, but no other abnormalities were seen. When the rabbits were given ip bimolane 30 mg/kg on d 7-18 after mated, all the embryos were resorbed. On d 10 after mated ip a single dose of bimolane 74.4 mg/kg to the mice caused nanomelia (34%) and subcutaneous hematoma (55%). Therefore, teratogenicity of bimolane was observed in mice.

The cytostatic effects of triptolide on HeLa cells in different proliferation stages and cell cycle phases were studied by colony-forming units assay. An exposure of exponential-phase cells to triptolide 0.02-4.00 micrograms/ml for 0.5 h resulted in a biphasic-exponential dose-survival curve (n = 1, D0 = 0.3 micrograms/ml in the most sensitive population; D0 = 2.8 micrograms/ml in the more resistant population). The plateau-phase cells in the same conditions seemed to have lower sensitivity to the drug. The synchronized cells caused by excess TdR double block and the selective detachment of mitotic cells from monolayer were exposed to triptolide 0.06 micrograms/ml for 0.5 h. The sensitivity of cell cycle phases to the drug ranked as follows: S greater than G2, M greater than G1. The result showed that triptolide is one of the cell cycle phase non-specific agents, but more sensitive to S phase cells.

The proliferation of L 1210 cells ceased rapidly after they were exposed to homoharringtonine (HH) 1 microgram/ml during exponential growth phase. However, 25.3% of the cells were still able to form colonies in soft agar if HH was removed after 24 h of incubation (the colony-forming efficiency for control cells was 62.5%). The clonogenic cells survived from the treatment were still sensitive to HH-continuous exposure. The IC50 of the treated and control cells were 15 and 20 ng/ml, respectively. Yet, the sensitivity of the treated cells to cytarabine decreased enormously. For instance, the survival rate of HH-treated cells remained at 100% level after they were exposed to cytarabine 4-8 micrograms/ml for 1 h, but only 40% control cells survived from the same treatment. When cells were continuously exposed to HH 0.4 micrograms/ml, the colony-forming efficiency decreased exponentially as a function of exposure time. The T1/2 of the clonogenic cells was about 18 h. The DNA contents in L 1210 cells was measured with a flow-cytometer. The results showed that the cell-cycle progress in all cells was interrupted by HH, regardless which phase they belonged to. So the cells seemed to be in a "frozen" state and the histogram unchanged.

RII, a new analog of retinoic acid, is an effective anticarcinogenic drug. The pharmacokinetic characteristics of RII were studied by HPLC in thirteen cancer patients after oral administration. The sensitivity to detect RII was greater than 3 ng and CV values of duplicate samples were 1.88-6.62. The results showed that peak concentration of RII in plasma appeared at 8 hrs after oral administration of 200 mg of the drug, and the mean peak concentration in serum was 3.612 +/- 1.099 micrograms/ml. Half life time (T1/2) was 6.62 +/- 0.81 hrs. The area under the drug-time curve (AUC) was 35.70 +/- 14.46 micrograms hr/ml. The results indicate that it is advisable to take RII twice a day.

Nude mice, inoculated with LAX 83 in bilateral subrenal capsules, were used in experimental therapy with 8 antitumor drugs. Treatment was initiated 2 d after tumor inoculation. All the drugs were ip to the nude mice daily for 7 d. At the daily doses VCR 0.4, MMC 2, CCNU 16, cis-DDP 2, AdM 2.5, 5-Fu 30, CTX 40 and MTX 2-6 mg/kg, the inhibition of the tumor growth were 100, 95.8, 91.3, 79.2, 65.2, 60.7, 62.3 and 0%, respectively. The results indicated that the effects of the drugs on nude mice inoculated with LAX-83 in subrenal capsule not only exhibited a good correlation to those in sc, but also shortened the period of experiment from 22 to 11 d. Furthermore, when LAX-83 was inoculated into the subrenal capsule of Swiss +/+ mice, the tumor tissues degenerated and disintegrated 2 d after the inoculation and replaced by inflammatory granuloma tissues 6 d later.

The survival curves of MGc80-3 cells exposed for 24 hr to various concentrations of 10 anticancer drugs were obtained by means of colony-forming assay. Comparison of drug doses required to reduce cell survival by 90% (ID90) with the clinically achievable peak plasma drug concentration (PPC) showed that MMC, ADM, and 5-Fu had strong cytotoxicity (PPC/ID90 = 18-36), whilst the other drugs were less effective (PPC/ID90 less than or equal to 11). The fact that MMC, ADM, and 5-Fu are most effective in the treatment of gastric cancer suggests that the cell line MGc 80-3 may still retain its original drug sensitivity which is consistent with that noted in clinical gastric cancer. This cell line could be useful in screening for new compounds with activity against this disease.

Bleomycin A6 is an antineoplastic antibiotic. Toxicologic study showed that the LD50 values of bleomycin A6 in mice were 92 +/- 7.4 mg/kg (IV), 72 +/- 5.6 mg/kg (IM), 82 +/- 4.5 mg/kg (SC), 102 +/- 0.6 mg/kg (IP) and 520 +/- 0.1 mg/kg (PO), respectively. Wistar rats were divided into 6 groups. Doses of 20, 10, 5, 2 and 0.5 mg/kg/day were given intraperitoneally every other day for 60 days. Renal damage to various degrees was found in rats with doses higher than 2 mg/kg. However, no pathologic changes were observed in the liver, heart, lungs, spleen, stomach, intestines, pancreas or brain. Three groups of dogs (3 in each group) were injected i.v. every other day for 60 days with a dose of 1.0, 0.5 and 0.1 mg/kg, respectively. The three dogs receiving 1.0 mg/kg died between the 4th and 7th week. Dogs treated with 1.0 and 0.5 mg/kg had renal damage and skin ulceration. With a dose of 0.1 mg/kg, dogs showed good tolerance and no renal damage was found. Multiple doses of bleomycin A6 injected into rabbit muscles caused no obvious local changes. After IV injection into rabbits, the maximal serum concentration of bleomycin A6 was 18.5 micrograms/ml, having a half life of 2.8 hours and 7.7% of the drug were excreted in the urine within 12 hours.

By using soft agar colony-forming assay, a monoclonal subline of human promyelocytic leukemia HL-60 cells was isolated and inducing activity of differentiation of a new retinoid R-81001 on the cells was studied. Phenotypic changes, such as biologic behavior, morphological and biochemical characteristics, show that R-81001 can induce HL-60 cells to differentiate along the myeloid pathway.

The thermotolerant kinetics of HEp-2 cells and its effect on cytotoxicity of Nitrocaphane (NC) were studied by colony formation assay. HEp-2 cells were exposed to two equal thermal doses (44 degrees C, 30 min) spaced at 0-24 hr intervals during which the cells were incubated at 37 degrees C. The maximum thermotolerance developed at the 8th hr and then gradually declined. Thermal dose survival curve even up to 2.5 hr of continuous exposure to 44 degrees C, no development of thermotolerance was demonstrated. If the cells were preheated at 44 degrees C for 30 min, and returned to 37 degrees C for 10 hr and then received the second heating at 44 degrees C for 3 hr, the slope of survival curve decreased (D0 = 2.26 hr). Thermotolerant ratio was 5.9. Thermosensitive HEp-2 cells were turned into thermotolerant cells by preheating at 44 degrees C, 30 min and returning to 37 degrees C for 10 hr. The thermotolerant cells showed resistance to drug or heat when they were exposed to NC or NC combined with heat.

By methods of human osteosarcoma cell culture in vitro, 3H-TdR isotope incorporation, gas chromatography and animal test, experimental observations were made on acrylic bone cement containing antitumor drugs. The results were as follows: 1. BLMA5, DACT, Ara-c, CDDP, and ADM were more thermostable. It is possible that these drugs can endure the polymerizing heat of bone cement. 2. The effective release of BLMA5, Ara-c and DACT from bone cement persisted over 2 months. 3. Scanning electron microscopy revealed that drug particles in the bone cement decreased or disappeared after immersion of the cement in tissue culture medium or implantation of it in animal bones. This shows that drug particles can be released from bone cement in vitro or in vivo 4. Animal experimental demonstrated that the bone cement containing BLMA5 or Ara-c had no effect on the healing of soft tissue, and the injury in local bone and bone marrow adjacent to the bone cement was slight and could recover in 4-8 weeks. 5. The release of residual monomer from polymerized bone cement continued as long as one month. Although the residual monomer inhibited the growth of tumor cells slightly during the early stage, it was far from being as effective as medicated bone cement.

Cytotoxic effect of hyperthermia combined with Nitrocaphane (NC) on HEp-2 cells was detected by colony formation assay. The results showed: 1. There was significant synergetic effect on survival fraction of HEp-2 cells when the heat was at 43 degrees C and 44 degrees C and NC at 0.5-4.0 micrograms/ml; 2. There was almost no effect on the cell survival when the heat was at 39 degrees C and 41 degrees C for 1 hr without NC; however, the cytotoxicity of NC (1.0 micrograms/ml) was enhanced when temperature was at 39 degrees C and 41 degrees C; 3. The sequence between heat and NC could influence the synergism. When the heat at 43 degrees C, 60 min and NC at 1.0 micrograms/ml were used simultaneously, the cytotoxicity was the strongest (SF = 0.025). When the heat was given 1-4 hr before or after the drug, the cytotoxicity was decreased. These results suggest that, over the range of 39-44 degrees C, the synergetic effects of hyperthermia and NC on malignant HEp-2 cells provide certain cell biologic basis for clinical application of local or systemic hyperthermia combined with NC.

Seventy-four cases of cervical carcinoma IIb were treated by radical surgery. Among them 38 patients had received additionally preoperative intra-arterial chemotherapy. The ten and five-year survival rate of those receiving preoperative intra-arterial chemotherapy were 62.5 and 73.3% respectively, while in the group without preoperative intra arterial chemotherapy, the ten and five-year survival rate were 21.4 and 38.9% respectively. The pathological picture of them were studied. The tissue destruction was found more severe and the cellular immune reactions around the tumor foci increased in cases receiving preoperative chemotherapy as compared with those without. The mechanism of tissue reactions related to chemotherapy was discussed.

Established human cancer cell lines derived from liver cancer (BEL-7402), nasopharyngeal cancer (CNE-2) and stomach cancer (MGC-803) were used in this study. These human cancer cells have been serially transplanted in nude mice. As determined by clonogenic assay, pingyangmycin (bleomycin A5) was highly cytotoxic to these three cell lines, of which the liver cancer cell line was more sensitive than the other two. At a tolerated dose level, pingyangmycin exhibited a remarkable growth inhibition on the growth of the liver cancer and stomach cancer xenografts, the inhibition rates being 70% and 85%, respectively. No pathologic changes were found in the organs of treated animals.