To explore the effects of retrovirus-mediated bcl-2 antisense RNA on apoptosis of leukemic cells.

To study the possible apoptosis-inducing effect of arsenic trioxide on human hepatocarcinoma (HCC) cells, and its molecular mechanisms.

Colcemid (COM) was tested for induction of meiotic delay and aneuploidies in meiotic metaphase II (MMII) of male(101/E 1 XC 3 H/E 1)F 1 mice post single intraperitoneum (i.p.) injection. The dose of 1 mg/kg of COM was used and sampled at 2, 6, 10, 14 and 18 h after COM treatment. The number of MMII and MMI were the highest at 2 and 6 h repectively, and decreased rapidly with lengthening of COM treatment and reached the lowest at 14 h; then increased. However, the ratio of MMII to MMI was always significantly higher than in solvent control at every sample interval. Under our experimental conditions, COM did not show aneugenicity in male mouse germ cells. The possible mechanisms by which COM caused meiotic delay and reasons that COM did not induce aneuploidy in MMII were discussed.

In order to elucidate the relation between cell signal transduction and cell differentiation, the effect of two differentiation inducers--all trans-retinoic acid (ATRA) and 13 cis-retinoic acid (13 cis-RA) on the specific activities (nmol/hr.mg protein) of phosphatidyl choline specific phospholipase D (PC-PLD) in 7721 human hepatocarcinoma cell line was studied. It was found that ATRA and 13 cis-RA increased the specific activities of membrane bound PC-PLD on 2nd and 4th day of cell culture respectively. If the PC-PLD activities were calculated as activity per bottle cells, the effect of ATRA on the 2nd day was also higher than that of 13 cis-RA, while the reverse was true on the 4th day, revealing a postponed effect of 13 cis-RA as compared with ATRA. The increase of PC-PLD was higher when the culture medium was refreshed every day than that when the medium was unrefreshed, suggesting that a factor might be existed in the fresh medium which could enhance the stimulating effect of retinoic acids on PC-PLD. The effect of ATRA on PC-PLD specific activity were higher on 2nd day than that on 4th day, owing to the accelerated proliferation of the cells on 4th day, leading to the increase of protein contents and decrease of the enzyme specific activity calculated on the base of protein contents. Whereas, the effect of 13 cis-RA on PC-PLD specific activity were higher on 4th day than that on 2nd day, because the increase of enzyme activity was higher than the increase of protein contents on 4th day. The relation between the elevation of PC-PLD and protein kinases was further studied and discovered that ATRA decreased both the specific activities of membrane bound and cytosolic protein kinase C (PKC) as well as tyrosine protein kinase (TPK) either in 2nd or 4th day of cell culture, which indicated that the increasing effect of ATRA on membrane bound PC-PLD was not resulted from the stimulating effect of PKC and TPK on PC-PLD, and its mechanism remains to be further investigated.

The HEL cells, a human erythroleukemia cell line, express mainly the fetal globin gene and small amount of the embryonic (epsilon) globin gene, but not the adult (beta) globin gene. Hydroxyurea, a small organic compound, has been successfully used to treat sickle cell anemia and beta-thalessaemia. Our data demonstrated that the growth rate of HEL cell proliferation was inhibited by different doses of hydroxyurea (from 50 mumol/L to 200 mumol/L). Using both routine RT-PCR and quantitative PCR analyses, we revealed that the expression of beta-globin gene was sharply activated and alpha-globin gene was almost completely silenced when HEL cells were induced for 3 or 5 days. Meanwhile, gamma-globin gene was expressed with no much difference between induced and uninduced HEL cells. We also demonstrated that the expression of GATA-1 and NF-E 2, which were two of the most important transcription factors in erythrocyte development, was activated about 3 folds in the induced cells. We suggested that the induction of GATA-1 and NF-E 2 expression by hydroxyurea might lead to activation of the adult beta-globin gene through some pathways of signal transduction, therefore, hydroxyurea might play a role to induce HEL cells to terminal differentiation.

To study the emechanisms of 10-Hydroxycamptothecine (HPT) inhibiting human urinary bladder cancer.

To assess the genetic stability of doxorubicin resistant sarcoma 180 cell line(S-180R) after in vivo passages.

To investigate the gene regulation of taxol-induced apoptosis.

Evaluating the effect of apoptosis induced by anticancer drugs on human B lymphocytic leukemia cell lines (Nalm-6) and their cell cycle specificity.

In order to search for new tumor differentiation inducer, the effects of matrine of Chinese herbal origin on differentiation of K562 cells and its mechanism were studied.

To study the mechanism of garlic oil-induced differentiation of human gastric cancer cell line BGC-823.

To clone the gene associated with apoptosis induced by an inhibitor of polyamine biosynthesis, alpha-difluoromethylomithine (DFMO).

To study the anti-emetic effect of Zudan on high-dose cisplatin and its toxicity.

To evaluate the efficacy and toxicity of China-made paclitaxel in patients with a variety of advanced malignancies.

To study the effect of 8-Chloro-adenosine (8CA) on tumor cell growth and apoptosis.

To further evaluate the clinical usefulness of ondensetron(OND, supplied by Qilu Pharmaceutical Company) with modified regime in the prevention of cisplatin (DDP)-induced nausea and vomiting.

To study programmed cell death (PCD) in two human acute myelocytic leukemia cell lines in different differentiated phases, NB4(AML3) and HL-60(AML2).

To investigate the effect of Ad-IL-2 and Ad-IL-3 on immunological recovery.

To evaluate the efficacy and the side effects of paclitaxel (Tesu) in breast cancer patients.