Recurrent chromosome changes in 31 primary ovarian carcinomas detected by comparative genomic hybridization

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Identification of a minimal overlapping amplified region at 19q13.1-q13.2 in four ovarian cancer cell lines

Program no. 361postprin

The significance of cyclooxygenase-2 expression in human hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the five most common malignancies in the world and is the second leading cause of death in Hong Kong. Previous studies have shown increased levels of cyclooxygenase-2 (COX-2) in a variety of human malignancies including HCC, suggesting that abnormal COX-2 expression plays an important role in carcinogenesis. In addition, some evidence suggests that selective COX-2 inhibitors suppress the formation of tumors in experimental models. However, there are no data in the literature on using COX-2 as an inhibitor target in HCC. The main objective of this article was to give a brief summary of the recent findings of the role of COX-2 in HCC. We briefly reviewed the significance of COX-2 in varies cancers, and then focused on the recent findings of the significance of COX-2 in HCC. Finally, we further evaluated the possibility of using COX-2 as a therapeutic target in HCC. © 2005 Elsevier SAS. All rights reserved.link_to_subscribed_fulltex

The effect of cyclooxygenase-2 (COX-2) inhibitor, Celecoxib, on xenograft of hepatocellular carcinoma (HCC) in nude mice

Oral Presentatio

The significance of cyclooxygenase-2 in hepatocellular carcinoma

Abstrac

Celecoxib suppresses the HCC development via the cell cycle arrest

Liver cancer is the second leading cause of death in males in Hong Kong and the incidence rate of 36 per 100,000 is the second highest in the world. Previous studies have shown increased levels of cyclooxygenase-2 (COX-2) in a variety of human malignancies including hepatocellular carcinoma (HCC), suggesting that abnormal COX-2 expression plays an important role in carcinogenesis. In addition, some evidence suggests that selective COX-2 inhibitors suppress the formation of tumors in experimental models. However, there is no data in the literature on using COX-2 as an inhibitor in HCC. Hence, we performed in vivo studies to investigate the chemopreventive and therapeutic effects of Celecoxib, a selective COX-2 inhibitor, on the development and growth of HCC xenograft in nude mice. To investigate the chemopreventive effect of Celecoxib, the drug was administered at day 0 by post tumor cell injection, while the control group was given vehicle only. To investigate the therapeutic effect of celecoxib on established tumor, the drug was administered at the 100 mm3 while in the control group only vehicle was given. Celecoxib was administered orally at a dose of 250-mg/kg body weight/day. Our results showed that Celecoxib could prolong the latent period (p<0.001) of HCC xenograft development in nude mice and decreased the growth of established HCC xenograft in nude mice significantly (p=0.03). However, there was no significant decrease in MVD and apoptotic index in treatment groups compared with the control groups. In in vitro studies, we have confirmed that the Celecoxib cannot induce apoptosis significantly in PLC and Hep3B HCC cell lines in the concentration of IC50. But Celecoxib at IC50 can significantly induce apoptosis in HUVEC cell line. Interestingly, the Celecoxib can induce G1 arrest in both HCC cell lines but not induce cell cycle arrest in HUVEC cell line. We have found that the cyclin D1 decreased as the concentration of Celecoxib increased. With these evidences, it suggests that the Celecoxib drug is acting on the cell cycle pathway rather than on the apoptotic pathway in HCC cells. Furthermore, our cDNA microarray data suggests that the Celecoxib is also acting on a coagulation pathway beside the cell cycle pathway. We have found that the fibrinogen fragments A & B, kininogen, etc are downregulated as treated with Celecoxib. In conclusion, our data suggest that the selective COX-2 inhibitor, Celecoxib, can delay the development of HCC and suppress the growth of established HCC in experimental animals most likely via the growth arrest pathway. COX-2 inhibition appears to be a promising strategy for chemoprevention and treatment of HCC which deserves further investigation and clinical trial

Isolation of a novel candidate oncogene within a frequently amplified region at 3q26 in ovarian cancer

Amplification of 3q25-q26 was one of the most frequent chromosomal alterations in human ovarian carcinoma. A chromosome microdissection hybrid selection method was applied to isolate transcribed sequences from a primary ovarian cancer containing high-copy-number amplification of 3q26 using 3q26 band-specific DNAs generated by chromosome microdissection. Using this method, we have isolated a novel candidate oncogene eIF-5A2 (eukaryotic initiation factor 5A2). eIF-5A2 shares 82% identity of amino acid sequence with eIF-5A including the minimum domain needed for eIF-5A maturation by hypusine modification at lysine-50 residue. Amplification and overexpression of eIF-5A2 was frequently detected in primary ovarian cancers and ovarian cancer cell lines. The proliferation-related function of eIF-5A supports that eIF-5A2 is a candidate oncogene related to the development of ovarian cancer.link_to_OA_fulltex