Boanmycin (bleomycin A6, BAM) was found to markedly inhibit the spontaneous pulmonary metastasis of Lewis carcinoma in mice. Compared at equitoxic doses (1/9 LD50), BAM was more effective than mitomycin. Minocycline (MNO) at 5 mg.kg-1 showed no inhibition on the growth of sc transplanted Lewis primary tumor; however, it markedly potentiated the antimetastatic effect of BAM. Treated with BAM (5 mg.kg-1) alone, the number of total metastatic foci and that of large foci (> 2 mm in diameter) in the lung were suppressed by 67% and 85%, respectively. When BAM was used in combination with MNO, the number of those foci was further reduced by 88% and 100%, respectively. By NAG enzyme assay, MNO was not cytotoxic and showed no synergism with BAM against PG cells, a cell line derived from a highly metastatic human giant cell carcinoma of the lung. Determined by ELISA with a monoclonal antibody, the expression of type IV collagenase in PG cells was remarkably inhibited by MNO. The intracellular free Ca2+ level in PG cells was reduced from 76.7 nmol.L-1 to 42.2 nmol.L-1 by MNO treatment. The study suggests that the combination of boanmycin and minocycline may be useful for control of tumor metastasis and the inhibition of type IV collagenase expression may be involved in the mechanism of minocycline potentiation.

4-[4"-(2",2",6",6"-tetramethyl-1"-piperidinyloxy) amino]-4'- demethylepipodophyllotoxin (GP-7) is a new podophyllotoxin spin-labeled derivative. Its primary effect is the antitumor activity on transplanted mouse tumors and cultured tumor cells. This paper describes a method for its determination using HPLC with UV detection and the determination of its pharmacokinetic parameters in rats. A Shimadzu LC-6A liquid chromatograph equipped with a Shimadzu SPD-6AV multiwavelength detector and a Chromatopac C-R3A data processor was used. The separation was performed on a Zorbax-ODS column (5 microns, 4.6 mm x 150 mm) with a mobile phase of methanol--water--glacial acetic acid (59:41:0.6). The flow-rate was 1.0 ml.min-1 and detection was made at 285 nm. A plasma specimen (0.2 ml) was spiked with 22.6 micrograms.ml-1 internal standard (podophyllic acid piperidinyl hydrazone nitroxide radical, GP-1) and extracted with ether--dichloromethane (3:1). The extract was evaporated at 45 degrees C. The residue was taken up with 0.1 ml of the mobile phase and 20 microliters aliquots were injected into the system. The calibration curve was linear in the range from 2 to 200 micrograms.ml-1 with r = 0.9997. The detection limit was 0.2 microgram.ml-1 and the recovery of GP-7 from rat plasma was 94.3%-100.9%. The relative standard deviations for within- day and between-day were 2.29%-4.64% and 5.55%-7.70%, respectively. After iv injection of GP-7 10, 20 and 30 mg.kg-1, the concentrations of the drug in rat plasma were determined. The pharmacokinetic parameters of GP-7 were obtained by using MCPKP program on a COMPAC-486 computer. The data obtained fitted a two-compartment open model, and the mean T1/2 beta value was 39.8 +/- 10.8 min.

The molecule of C1027, an antitumor antibiotic with extremely potent cytotoxicity against cultured cancer cells, is composed of an enediyne chromophore and an apoprotein of 10.5 kDa. These two parts of the molecule, connecting each other through non-covalent binding, can be dissociated and reconstituted. As determined by clonogenic assay, the chromophore served as the active part of the molecule, displaying potent cytotoxicity similar to that of intact C1027. The activity of free chromophore decreased more rapidly than that of intact C1027, indicating that apoprotein played a role in protecting the chromophore from inactivation. By incubating together in phosphate buffer, the chromophore and apoprotein were reconstituted to form an intact C1027. The ratio of chromophore and apoprotein remained 1 : 1 in the reconstituted molecule, even though extra amount of chromophore was added. The optimal condition for the reconstitution was pH 7.0, at 20 degrees C for 12 h. When the disulfide bond of the apoprotein was reduced by DTT, the activity of C1027 decreased more rapidly. C1027 was digested by pronase and the produced fragments of various molecular weights were examined by capillary electrophoresis. The cytotoxicity of 3-5 kDa fragment approximated that of intact C1027 and its IC50 value was 0.07 fmol.L-1. The results indicate that the intactness of the apoprotein is not indispensable for stabilizing the chromophore and a smaller molecule of 3-5 kDa consisting of a peptide fragment and a chromophore may retain full C1027 activity.

The effect of HH07A on the growth of tumor cells in vitro was investigated using the techniques of cell growth curve determination and soft-agar colony-forming assay. The result showed that HH07A inhibited the growth of L1210 cells and HL-60 cells at a concentration of 1.5 micrograms.ml-1 and 4.0 micrograms.ml-1, respectively. Among the cells tested, L1210 cells were shown to be the most sensitive, followed by KB cells and HL-60 cells (with IC50 of 2.29, 4.13 and 4.36 micrograms.ml-1, respectively). Normal mouse granulocyte-macrophage progenitor cells (GM-CFC) were less sensitive to the drug (with IC50 of 11.15 micrograms.ml-1) as compared with the tumor cells. As they were exposed to HH07A 3.5 micrograms.ml-1 for 5 days, HL-60 cells did not show NBT reductive ability. Intraperitoneal injection of HH07A exerted inhibitory effect on the ascitic tumors of L1210 and S180 in mice. Oral or ip administration of HH07A also showed some effect on S180 solid tumors in mice.

8-chloroadenosine showed marked activity against mice solid tumor hepatoma 22 (H22) and ascitic leukemia L-1210. At 100mg. Kg-1. /d x 7, the inhibition rate of H22 was 71.7 +/- 13.3% (P < 0.01) and 66.1 +/- 4.46% (P < 0.01), i.p. and i.v., respectively; at the same dose, the life-prolonging rate of mice bearing L-1210 was 124.0 +/- 22.1% (P < 0.01) and 104.2 +/- 20.1% (P < 0.01), i.p. and i.v., respectively. 8-chloroadenosine also showed activity against 3 human cancer cell lines in vitro. The IC50 values were determined by measuring cell growth using trypan blue dye exclusion. The results showed that HL-60 and K562, and human gastric cancer cell line MGc80-3 and IC50 values of 1. 8 mumol/L, 4.2 mumol/L and 1.56 mumol/L, respectively. The toxicity of 8-chloroadenosine was low, with LD50 of 1025.0 +/- 52.4 mg/kg for mice and 793.4 +/- 70.1 mg/kg for rats by single i.p. injection.

Gnidimacrin, a diterpene compound, isolated from the methanol extract of Stellera chamaejasme L, showed significant antitumor activities against mouse leukemia P-388 and L-1210 in vivo. At the dosages of 0.02-0.03mg/kg ip, the in increase in life span (ILS) was 70% and 80%, respectively. Gnidimacrin was also active against murine solid tumors in vivo, such as Lewis lung carcinoma, B-16 melanoma and colon cancer 26. It showed ILSs of 40%, 49% and 41% at the dosages of 0.01-0.02mg/kg ip, respectively. Gnidimacrin strongly inhibited cell proliferation of human cancer cell lines such as leukemia K562, stomach cancers Kato-III, MKN-28, MKN-45, and mouse L-1210 by the MTT assay and colony forming assay in vitro. The IC50 of gnidimacrin was 0.007-0.00012microgram/ml. It is concluded that gnidimacrin is the principal antitumor element in Stellera chamaejasme L. with strong antitumor activities.

Precancerous pathological changes of colon was induced by single injection in a short-term and multiple injection in a long-term intraperitoneally with 1,2-dimethylhydrazine (DMH) in NIH mice and Sprague-Dawley rats. And, protective effects of spirulina, germanium-132 and vitamin E on colon aberrant crypts induced by DMH were observed. Results showed either single injection or multiple injection with DMH could induce aberrant crypts in colon. The number of aberrant crypts scattered by short-term single injection was less than that by multiple one, and less of the aberrant crypts foci were formed by short-term single injection. Spirulina powder, germanium-132 and vitamin E all could inhibit the function of aberrant crypts of colon. In the ninth week during multiple injection with DMH, a lot of aberrant crypts of colon had been induced, and a certain amount of aberrant crypts foci had been generated. The number of aberrant crypts and aberrant crypts foci in the animals with tumor increased with the length of DMH injection. In the ninth-, 13th- and 16th-week, respectively, the number of aberrant crypts and aberrant crypts foci was significantly less in animals protected by spirulina than in positive controls (P < 0.01), but there was no significant difference between them during 21st- and 24th-week of injections.

As a drug for lymphosarcoma, pingyangmycin (A5) is not widely used because of its toxicities, short half-life and low affinity to lymph. For the purpose of delivering A5 to the lymph system to strengthen and sustain its effects and to lower its toxicities, its gelatin microspheres-in-oil emulsion (S/O) was studied in vitro and in vivo. By ultrasonication, gelatin microspheres with diameters of 1.67 +/- 0.69 microns were homogeneously dispersed in oil to form the S/O, which was a pseudoplastic flow and stable under 0 degrees C for at least 1 month. With the content of 14.03 +/- 0.15 mg.ml-1, A5 released from the emulsion in a zero order rate with t0.5 of 12.0 h. In vivo experiments showed that the S/O emulsion exhibited potent lymphotropicity, prolonged plasma concentration and a probably lower pulmonary toxicity.

Lung targeting gelatin microspheres of mitoxantrone (DHAQ) were prepared by a two-step method. The diameter of 87.36% of the DHAQ gelatin microspheres (DHAQ-GMS) was in the range of 5.1 to 25.0 microns. Release of the drug from the DHAQ-GMS in vitro became much slower and its t1/2 was 4 times longer than that of pure DHAQ. The characteristic peak of heat absorption on the differential thermal analysis curve was at 133 degrees C and almost no change was observed after the DHAQ-GMS were stored for 3 months at 37 degrees C (relative humidity 75%). The distribution test in vivo in mice indicated that the lung targeting effect of the DHAQ-GMS was obvious and that the targeting efficiency of the lung compared to other organs and blood increased 3 to 35 times. Kinetic behavior of the drug in mouse lung could be described by one open compartment model, and the average residual time increased by 10 h.

An optimum procedure was established by orthogonal test for preparing cis-platin albumin microspheres (CDDP-AMS) with emulsion-heating stabilization method. The factors which affect particle size and release rate in vitro were studied. The particle size focusing on 58.8-256 microns, the mean size was 148.46 microns, drug content was 51.16% (w/w). The dissolution profiles of the CDDP-AMS followed Higuchi kinetics. In rabbits the distribution and elimination half times of platinum were prolonged 3.36 times and 1.23 times vs injection group, respectively, after hepatic arterial chemoembolization with CDDP-AMS. The highest serum concentration of platinum is 30 percent of that of the injection group. The platinum concentration was increased in liver (P < 0.01) and decreased in kidney (P < 0.05) vs that of injection group.

The L1210 cells rapidly ceased to proliferate and its mitotic index decreased markedly after being exposed to HH07A 2 micrograms . ml-1 during exponential growth phase. However, 34.6% of the cells were still able to form colonies in soft agar if HH07A was removed after 24 h of incubation (the colony-forming efficiency for control cells was 63.7%) and the cell viability remained at about 94%. The DNA contents in L1210 cells were measured with a flow-cytometer. The results showed that the cell-cycle was blocked at the S phase and the number of cells in G2 + M phase decreased significantly. The time response course for L1210 cells indicated that the inhibitory effect of HH07A on L1210 clonogenic cells was slightly time dependent.

By using MTT and trypan blue exclusion assay, the sensitivity of retinoic acid sensitive HL-60 and resistant HL-60/RA cell to six anti-leukemia drugs such as RA, Ara-c, harringtonine was compared. It was found that all five drugs except RA exhibited an approximately equivalent IC50 to HL-60 and HL-60/RA cells. The results suggest that tumor cells may not develop resistance to differentiation inducer and cytotoxic anti-tumor agent parallel. It also suggests that it is reasonable to use a combination of differentiation and cytotoxic anti-leukemia agents concomitantly or sequentially.

4-hydroxycarbophenyl retiamide (R II) is a new synthetic analogue of retinol, but with lower toxicity than retinoic acid. We studied its induction effects and its effects on some malignant phenotypes of the MFC cell line. The mechanism of these effects was also explored. MFC cells were grown in complete RPMI 1640 medium supplemented with 10(-5) mol/L R II for five passages. By then the cell growth rate slowed down; the rate of 3H-TdR incorporation and the colony-forming capacity of MFC cells decreased; morphologically, the cells became epithelial rather than fibroblastic with various degrees of polarization. Further investigation about the mechanism of these changes was also undergone. First by flow cytometry, it was shown that the R II-treated cells were retained in G1 phase. Second, dot blot hybridization showed a decrease of more than 61% of c-myc mRNA and an increase of more than 52% of v-fos mRNA. The major chromosome distribution changed from 54-56 to 46-54 with an increase in diploid. Scanning microscopic examination showed that the R II-treated cells were covered by numerous microvilli and pseudopodia with round terminal expansion in contrast to the ruffle protrusions and leaf-like pseudopodia of control cells. All the results suggested that R II could reverse some malignant phenotypes of MFC cells.

In this study, castor seeds were processed by one of the traditional Chinese methods, LD50 was measured and tumor inhition tests in nude mice bearing human pulmonary carcinoma were conducted. The results showed that the processing method was able to lower the toxicity of castor seeds and maintain their antitumor effect, thus providing an experimental basis for oral administration of castor seeds in the therapy of pulmonary carcinoma.

Two ovarian cancer cell lines, 3AO and NIH: OVCAR-3, were used in this study to assess the synergistic effect of TNF and IFN gamma in combination. The result showed that these two ovarian cancer cell lines were all resistant to TNF and IFN gamma individually, but sensitive to the combined administration of TNF and IFN gamma. Concentration of 1 x 10(4) U/L of TNF and IFN gamma significantly inhibited 3AO and NIH: OVCAR-3 ovarian cancer cells (P < 0.05). Administration of 1 x 10(6) U/L TNF and IFN gamma could inhibit the growth of 3AO cells by 55% and NIH: OVCAR-3 cells by 75% (P < 0.01). It suggests that in some ovarian cancer cells which resistant to TNF could be changed to TNF sensitive cells by IFN gamma. anticancer treatment higher antitumor activity could be achieved by combined administration of TNF and IFN gamma.

In this paper, the species, ecology and distribution of the medicinal plants of Thalictrum in Gansu Provinceare are reported. Eleven species and 4 varieties have been found good for medical use. Their effectiveness and chemical composition have also been discussed.

We developed two leukemic cell lines (K562 HHT and L1210 HHT) stably 16.7 fold and 13.4 fold resistant to HHT respectively with which the culture were treated. Both cell lines were also cross-resistant to DOX, VCR, DNR and Mel. Increased expression of MDR1 gene in the both lines was noted. To further evaluate the implications of MDR1 in HHT resistance. We studied the expression of MDR1 in sensitive and HHT-resistant sublines of K562 by ABC with an monoclonal antibody against P170, JSB-1. K562 HHT cells were positive but sensitive cells were negative. Additionally, the increased drug resistance was associated with increased level of expression of alpha and pi class GST gene, but not with increased level of expression of mu class GST gene.

We examined the cytotoxic activities of recombinant human tumor necrosis factor (rHTNF-alpha) and five chemotherapeutic agents, CTX, 5-Fu, VCR, DDP, KSM, against two human ovarian cancer cell lines, OVCAR3 and CAOV3, using the MTT assay. The results showed that cytotoxicities of rHTNF-alpha at 5 x 10-5 x 10(4) u/ml against OVCAR3 cell line for 24 h exposure were from 14.2 +/- 6.8% to 67.2 +/- 3.0%, and those 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-alpha. Further, we studied the combined anticancer potential of rHTNF-alpha with chemotherapeutic agents against the two cell lines. Various degrees of synergism in cytotoxicities of DDP or KSM in combination with rHTNF-alpha were observed. The cytotoxic effect of rHTNF-alpha on CAOV3 cell were also morphologically observed under phase contrast and electron microscope. Based on experiment in vitro, the in vivo anticancer activity of rHTNF-alpha alone or in combination with KSM was examined against human ovarian cancer OVCAR3 subcutaneously transplanted in nude mice. After 8 weeks of treatment, a statistically significant difference of mean tumor volume was found between the control group and groups that received rHTNF-alpha or rHTNF-alpha plus KSM (P < 0.01).