By using an inducer of differentiation (HMBA) and blockers of signal pathways, the relationship between two second-messenger pathways (DG-PKC, cAMP-PKA) in inducer-mediated MGc80-3 cell differentiation was studied. Cells were treated with HMBA for 24 h, levels of DG decreased by 64.7%, activity of PKC decreased by 28.7%, while levels of cAMP and rate of it's protein binding increased by 62% and 32.6% respectively (after treated for 48 h, the result was more remarkable). PKA-R II distributed in nuclei. H7 (PKC inhibitor) was used to substitute for HMBA to block the DG-PKC pathway. After treatment for 24 h, the levels of DG and activity of PCK both decreased, while the levels of cAMP increased 1.04 times. On the contrary, PKA inhibitor was added while HMBA was used to induce cell differentiation, cAMP-PKA pathway was blocked, levels of cAMP and rate of it's protein binding decreased. But levels of DG and activity of PKC both increased to the levels of control cells. At this time, PKA-R II distributed only in cytoplasm. These results suggest that harmonious relations of the positive and negative regulation of cAMP-PKA and DG-PKC systems in cells during the proliferation and differentiation of cells. It also showed that positive regulation of PI system may play a leading role in MGc80-3 cells. It let to normal regulation of two signal pathway out of control to remain malignant phenotype of these cells.

The primary donor tumor of these 2 models was a spontaneous pulmonary adenocarcinoma which was originally developed in a 23-month-old male 615 mouse in our laboratory. That mouse was sacrificed for s.c. transplantation to 2 isogeneic hosts on November 12, 1988. A total of 50 generations for diffuse type and 30 generations for nodule type have since succeeded. Nodule type: The incidence of serial s.c. transplantation of this type of tumor was 100% with a latency period of 4-7d, and the lifetime of the tumor-bearing mice was about 44d. Spontaneous metastatic rate in the lungs was 100% from the 1st to the 20th generations. Diffuse type: The incidence of the s.c. transplantation tumor was 100%. The latency period was 3-6 d and the lifetime of the tumor-bearing mice was about 22 d. The spontaneous metastatic rate in the lungs and lymph nodes (after the 7th generation) was 100% from the 1st through the 35th generations. The origin of these 2 types was the same and their morphological features were similar. But several of their biological characteristics (including drug sensitivity and s.c. transplantation tumor growth speed) were different.

The effects of fagopyrum cymosum rootin on four human tumor cells in vitro were observed in comparison with 5-Fu. It was found that the clonal formations of four human tumor cells were markedly inhibited and the inhibition rates were positively proportional to concentration. At the concentration of 12.5 micrograms/ml, inhibition rates were GLC 98.7%, Hela 53.8%, SGC 65.4% and KB 82.1%.

Transcatheter arterial embolization (TAE) using hydroxycamptothecin, cantharidin and cisplatin which were mixed thoroughly with lipiodol, combined with large doses interferon and interleukin-2 as adoptive immunotherapy were carried out in the treatment of 48 patients with unresectable advanced stage primary hepatoma, evaluation of therapeutic effect showed that partial remission rate was 54.2%, significantly higher than that of embolization group using chemotherapeutic agents alone (cisplatin, adriamycin and mitomycin), the partial remission rate was 32.1% (P < 0.01). The side effects of camptothecin and cantharidin including hematuria, urodynia were also successfully eliminated.

Siwenmycin, isolated from a streptomyces culture, is a new member of aclacinomycin analogues. It exhibited a remarkable inhibitory effect on the biosynthesis of DNA and RNA in vivo. In order to recognize the mechanism of the inhibitions, the reactions of siwenmycin to DNA template, DNA polymerase I and RNA polymerase were studied. Experimental results showed that siwenmycin could intercalate DNA, but it did not inhibit DNA polymerase I-mediated DNA repair replication and T7RNA polymerase-mediated DNA transcription. This indicates that siwenmycin is not a damage to the DNA template function, nor will it inhibit DNA polymerase I and T7RNA polymerase, though it can intercalate DNA.

Ion-chromatography of lyophilized cobra (Naja naja atra) venom on SP-Sephadex C-50 yielded 14 fractions, of which 7, 8, 9, and 10 possessed neurotoxic actions and 11, 12, 13, and 14 had cytotoxic activities. Chromatography of fraction 14 on SP-Sephadex C-25 gave cytotoxin-14. It was homogeneous on polyacrylamide gel electrophoresis with m = 7448 Da. It was a typical cytotoxin without phospholipase A2 activity and had a selective cytotoxic action on human cancer cell lines.

The cytotoxic activities of recombinant human tumor necrosis factor (rHTNF) and five chemotherapeutic agents, CTX, 5-FU, VCR, DDP, KSM, against two human ovarian cancer cell lines, OVCAR3 and CAOV3, using the MTT assay were studied. The result showed that cytotoxicities of rHTNF at 5 x 10(4)-5 x 10(7) U/L against CAOV3 cell line for 24h exposure were from 14.2% +/- 6.8% to 67.2% +/- 3.0%, and that against CAOV3 cell line were from 8.2% +/- 4.3% to 60.9% +/- 1.3%. The cytotoxic effects of all five chemotherapeutic agents against the two cell lines were much lower than that of rHTNF. Various degrees of synergistic enhancement cytotoxicities of DDP or KSM in combination with rHTNF were assessed. Especially, distinct synergistic effects of a low dose, 50kU/L, or rHTNF with nearly all concentration (10(-4)-10(-1) mg/L) of KSM were obtained on the two cell lines.

Probimane (AT-2153) is a new anticancer compound. It was first developed in this Institute. It is effective against mouse tumors S37, S180, Lewis lung carcinoma, L1210 and human pulmonary adenocarcinoma heterotransplanted into nude mice. In the present work, 14C was labeled at central dioxopiperazine or methyl morpholine group of probimane 120 mg.kg-1 was injected iv in mice bearing Lewis lung carcinoma by whole body autoradiography. The results showed that probimane was broken into at least two parts: a central part and a methyl morpholine group. The central part of compound hardly penetrated through the blood-brain barrier, but accumulated in the urinary bladder. The methyl morpholine group showed a high affinity to tumor tissue and accumulated in spleen, bone and liver.

Twenty patients with liver malignant tumors who were treated by hepatic artery occlusion previously, were treated with additional hepatic infusion or embolization though extrahepatic collaterals. Twenty eight courses of hepatic infusion were performed in 14 patients through the right phrenic artery, collaterals of the proper hepatic artery, collaterals of the superior mesenteric and the pancreaticoduodenal arcades, collaterals of the celiac artery, gastroduodenal artery and left gastric artery. Nine hepatic embolization procedures were performed in 5 patients through the right phrenic artery, collaterals of the proper hepatic artery, gastroduodenal artery and collaterals of right renal artery. No complication related to the treatment procedures occurred in this group. The 1-year and 2-year survival rates were 60% and 10%, respectively.

A multidrug-resistant cell line K562/A02 was obtained from its parent K562 by long-term adriamycin (ADM) induction and cloning selection. The K562/A02 has high expression of mdr-1 P-glycoprotein (P170), strong resistance to its induction drug ADM and some other anticancer drugs such as daunorubicin, VP16, homoharringtonine and amsacrine. Its intracellular concentration of daunorubicin is much lower than that in its parent K562, which can be partially reversed by cyclosporin-A and verapamil.

N-Alkyl polymethylene dicarboxamides are known potent inducers of erythroid differentiation in murine erythroleukemia cells. The most active inducer N,N,N',N'-tetramethyl-1, 6-hexane-dicarboxamide has the same effectiveness as HMBA which has entered clinical trials as a differentiating agent. These compounds also have inducing activity in HL-60 human promyelocytic leukemia cells. In this paper, the synthesis of a series of N,N'-bis[2-(2-thiazolinyl)], N,N'-bis[5-(1-methyl-2-pyridonyl)], N,N'-bis[3-(1-phenyl-5-pyrazolonyl)] polymethylene dicarboxamides and 3,3'-(polymethylene dicarbonyl)bis(1-methyl-2-imidazolidine-thiones) is reported. The inducing activities of the compounds were evaluated in vitro with HL-60 human promyelocytic leukemia cell line. Among them, N,N'-bis[2-(2-thiazolinyl)]-1,8-octamethylene- dicarboxamide (I4) and N,N'-bis[5-(1-methyl-2-pyridonyl)]-1,6-hexamethylenedicarboxami de (II3) were shown to be relatively effective inducers of differentiation.

In this paper 6 factors and 12 levels of each variable were selected by Uniform Design Method and computer for preparing albumin microspheres with emulsion-chemical cross-linking. An optimal procedure for preparing albumin microspheres was established and the mean diameter of albumin microspheres is 0.41-0.47 micron. Albumin was labelled with 125I-isotope and 125I-albumin microspheres were prepared according to the optimal procedure. The suspension of 125I-albumin microspheres with 0.1% Tween-80 saline was injected via mice tail vein. The animals were sequentially killed and the radioactivity of blood, spleen, liver, kidney, stomach, heart, lung, thyroid and brain were measured. The results showed that albumin microspheres were accumulated mainly in the liver, about 68% of the injected dose at the peak concentration. The pharmacokinetics of albumin microspheres in liver was also studied and two-compartmental model can be used to describe the regulation.

The preventive effects of Zn Glycyrrhizate (Gly-Zn) on lethal toxicity, nephrotoxicity, hemotoxicity, testicular toxicity and anticancer activity of cisplatin (CDDP) were investigated in mice. The toxicity of CDDP evaluated by the above criterion was significantly reduced by preadministration of Gly-Zn 400 mg.kg-1.d-1 x 5 (P < 0.05 or P < 0.01). The protective effects were better than bismuth subnitrate (BSN) which has been studied previously (0.05 < P < 0.1). The metallothionein (MT) level in the liver, kidney, heart and cancer of mice treated with one of these compounds were determined. The results showed that the levels of MT induced by Gly-Zn were significantly increased in liver and kidney (P < 0.05). It was just in conformity with the conclusion that the best protective effect appeared in the groups treated with preadministration of Gly-Zn. These results suggest that increased MT synthesis in the liver and kidney may be involved in the protective effect of Gly-Zn on the toxicities produced by CDDP. The experiments also showed that Gly-Zn did not affect the anticancer effect of CDDP in vitro and in vivo, while the MT level was not increased in cancer (P < 0.05), so Gly-Zn might improve the therapeutic index of CDDP.

Twenty four 4-acylamidc-4-deoxy-4'-demethylepipodophyllotoxins were synthesized by acylation of 4-amino-4-deoxy-4'-demethylepipodophyllotoxin by means of usual methods, and screened in vitro. This type of compounds showed strong antitumor activities, most of them are superior to etoposide in the inhibition against L1210 and KB cells.

This paper describes the cytotoxicity of ranunculin (RAN) and its mechanism of action. The IC50 of RAN against the KB and Bel7402 cells in colony test were found to be 0.21 and 0.35 mumol/L respectively. RAN inhibited the incorporation of 3H-labeled precursors into DNA and RNA of L1210 cells. RAN (15 mumol/L) markedly decreased DNA synthesis catalyzed by DNA polymerase I and promoted the generation of superoxide anions in DMSO/KO2 system. In the meantime, SOD and CAT were shown to partly revoke the inhibitory effects of RAN upon the incorporation of 3H-TdR into DNA. No direct reaction between RAN and DNA template was observed and no effect of RAN on DNA TOPO II or RNA polymerase was found. Our results suggest that the cytotoxicity of RAN in vitro may be due to inhibition of DNA polymerase and increase of oxygen free radicals.