CLN3 gene product is an antiapoptotic membrane protein, the expressions of CLN3 in normal tissues and cells are at very low level. Juvenile-Batten disease is a neurodegenerative disease caused by accelerated apoptosis of photoreceptors and neurons resulting from deletion of 1.02 kb in the CLN3 gene. A number of observations showed that CLN3 mRNA and protein are overexpressed in a variety of human cancer cell lines. Blocking of CLN3 expression using an adenovirus-expressing antisense CLN3 inhibited growth and viability of cancer cells. CLN3 may regulate apoptosis through modulating ceramide synthesis or the expression of some down stream genes. More importantly, these results suggested that CLN3 is a novel molecular target for the etiology, progression and theraputics of cancer.

Abstract-Eleven mouse monoclonal antibodies (McAbS)specific for human alpha-fetopr-otein(AFP) have been produced by the hybridoma technique. Immunodiffusion was us-ed for determining the immunoglobulin class and subclass of the McAbS. Seven of them are IgG; two are IgM. At least 4 different antigenic determinants on human AFPcan be recognized by using the McAbS and cross-two-site sandwich solid radioimmun-oassay. One of the McAbS can specially react with one of the fragments of AFP dig-ested by pepsin. In addition, the cross-reactivity among the AFPs of different mam-malian species was also tested by using the McAbS.

ObjectiveTo explore the molecular mechanism of neural tube defects (NTDs) caused by hyperglycemia and thiadiazole and the antagonistic effect of taurine MethodsThe pregnant mice were divided into hyperglycemia groups, thiadiazole group,taurine groups and control groups The mRNA and the protein of Pax3 or Cx43 gene were detected respectively by reverse transcription-polymerase chain reaction assay and immunohistochemical method ResultsAs compared with mice treated by thiadiazole-stomach-perfusing, NTDs were significantly increased from mice treated with glucose-injection when blood glucose levels were ≥ 13 4 mmol/L Elevated glucose and thiadiazole could cause changes in Pax3 and Cx43 expression Hyperglycemia had stronger developmental toxicity on mice embryos Expression of Pax3 (mRNA 0 97?0 20, protein 0 11?0 02) in hyperglycemia group was significantly decreased, while expression of Cx43 (mRNA 7 05?1 63, protein 0 94?0 05) was significantly increased, and the relationship of dose-effect was demonstrated In the thiadiazole group, the expression of Cx43 (mRNA 6 96?0 73, protein 0 92?0 12) was significantly stronger than control groups, but there were no significant differences in expression of Pax3 between thiadiazole and its control groups Both of their teratogenicity could be antagonized by taurine ConclusionsThis study suggests that congenital malformation associated with diabetic pregnancy is caused by disruption of regulatory genes,Pax3 and Cx43 expression in embryo in response to elevated glucose Thiadiazole can only disturb the regulation of Cx43 gene causing NTDs Taurine can correct the disruption caused by the two teratogens

OBJECTIVETo assess the effect of wild-type p53 gene on the chemotherapy sensitivity of ovarian cancer SKOV-3 cells to cisplatin.

METHODSRecombinant eukaryotic expression vector pcDNA3 containing full-length human wild-type p53 cDNA was introduced by lipofectamine-mediated gene transfection into SKOV-3 cultured cells which were acted on by cisplatin of different concentrations. The chemotherapy sensitivity of tumor cells with different-status p53 was observed.

RESULTSThe inhibitive rate of formation of clones after p53 cDNA transfection was 56.4% compared with the untransfected one. The formation of clones decreased by 76.2% and 84.1% respectively after being acted on by 0.5 ug/ml cisplatin for 24 hours and 48 hours respectively. The formation of clones decreased by 89.5% and 93.7% respectively after being acted on by 1 ug/ml cisplatin for 24 hours and 48 hours respectively. After the introduction of p53 cDNA, the S phase and the ratio of G(2)/M phase of tumor cells decreased, and the ratio of G(1)/G(0) phase increased. The introduction of p53 gene into cells led to cell cycle arrest in G(1) phase.

CONCLUSIONThe exogenous introduction of wild-type p53 cDNA into ovarian cancer SKOV-3 cells increased the chemotherapy sensitivity to cisplatin.

Antineoplastic Agents ; pharmacology ; Blotting, Northern ; Blotting, Western ; Cell Cycle ; physiology ; Cell Division ; drug effects ; genetics ; Cisplatin ; pharmacology ; DNA, Complementary ; genetics ; Dose-Response Relationship, Drug ; Female ; Genotype ; Humans ; Ovarian Neoplasms ; drug therapy ; genetics ; pathology ; Plasmids ; genetics ; RNA, Messenger ; genetics ; metabolism ; Time Factors ; Transfection ; Tumor Cells, Cultured ; drug effects ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; physiology