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Conference Paper: Genomics approach to identify growth factor and drug transporter associated with liver cancer recurrence and chemo-resistance

TitleGenomics approach to identify growth factor and drug transporter associated with liver cancer recurrence and chemo-resistance
Authors
Issue Date2012
PublisherSpringer New York LLC. The Journal's web site is located at http://www.springer.com/west/home/medicine?SGWID=4-10054-70-173733513-0
Citation
The 22nd Congress of the Asian Pacific Association for the Study of the Liver (APASL), Taipei, Taiwan, 16-19 February 2012. In Hepatology International, 2012, v. 6 n. 1, p. 26, abstract no. PS05-01 How to Cite?
AbstractBackground: Liver cancer is the third leading cause of cancer death globally. Surgery is the mainstay for early stage patients but recurrence is still common. Chemotherapy has been widely used to treat advanced liver cancer but with marginal efficacy. Recent evidences have shown the role of tumor initiating cells on chemo-resistance and recurrence, however, the key genes remind inconclusive. Recently, we have demonstrated that the novel growth factor granulin-epithelin precursor (GEP) and drug transporter ABCB5 were associated with chemo-resistance and recurrence-free survival (Gastroenterology 2011). GEP has been identified as a potential therapeutic target for liver cancer in our earlier genomic studies. The aim of the study is to identify additional drug transporters with clinical relevance. Methods: The liver cancer gene expression profiles reported previously were re-examined for all the ATP-binding transporters. The gene of interest were further validated in an independent cohort using real-time quantitative RT-PCR. Results: ABCF1 was upregulated in tumor compared with non-tumor (P/0.001), and increased ABCF1 was associated with poor recurrence- free survival (log-rank test, P = 0.001). Functionally, suppression of ABCF1 rendered the liver cancer cells sensitive to chemotherapeutic agents. Liver cancer cells that were positive for GEP and ABCB5/ABCF1 showed enhanced expression of the stem cell related signaling molecules-catenin, Oct4 and Nanog. Conclusions: In summary, chemo-resistance and cancer recurrence are dictated by a subset of cells expressing GEP and ABC transporters. Targeting the novel growth factor GEP and drug transporters, in combination with chemotherapy, could provide novel treatment modalities to eradicate the aggressive hepatic tumor initiating cells.
DescriptionOral Presentation
Persistent Identifierhttp://hdl.handle.net/10722/165656
ISSN
2015 Impact Factor: 1.125
2015 SCImago Journal Rankings: 0.669
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCheung, STen_US
dc.contributor.authorCheung, PFYen_US
dc.contributor.authorCheng, CKCen_US
dc.contributor.authorFan, STen_US
dc.date.accessioned2012-09-20T08:21:41Z-
dc.date.available2012-09-20T08:21:41Z-
dc.date.issued2012en_US
dc.identifier.citationThe 22nd Congress of the Asian Pacific Association for the Study of the Liver (APASL), Taipei, Taiwan, 16-19 February 2012. In Hepatology International, 2012, v. 6 n. 1, p. 26, abstract no. PS05-01en_US
dc.identifier.issn1936-0533-
dc.identifier.urihttp://hdl.handle.net/10722/165656-
dc.descriptionOral Presentation-
dc.description.abstractBackground: Liver cancer is the third leading cause of cancer death globally. Surgery is the mainstay for early stage patients but recurrence is still common. Chemotherapy has been widely used to treat advanced liver cancer but with marginal efficacy. Recent evidences have shown the role of tumor initiating cells on chemo-resistance and recurrence, however, the key genes remind inconclusive. Recently, we have demonstrated that the novel growth factor granulin-epithelin precursor (GEP) and drug transporter ABCB5 were associated with chemo-resistance and recurrence-free survival (Gastroenterology 2011). GEP has been identified as a potential therapeutic target for liver cancer in our earlier genomic studies. The aim of the study is to identify additional drug transporters with clinical relevance. Methods: The liver cancer gene expression profiles reported previously were re-examined for all the ATP-binding transporters. The gene of interest were further validated in an independent cohort using real-time quantitative RT-PCR. Results: ABCF1 was upregulated in tumor compared with non-tumor (P/0.001), and increased ABCF1 was associated with poor recurrence- free survival (log-rank test, P = 0.001). Functionally, suppression of ABCF1 rendered the liver cancer cells sensitive to chemotherapeutic agents. Liver cancer cells that were positive for GEP and ABCB5/ABCF1 showed enhanced expression of the stem cell related signaling molecules-catenin, Oct4 and Nanog. Conclusions: In summary, chemo-resistance and cancer recurrence are dictated by a subset of cells expressing GEP and ABC transporters. Targeting the novel growth factor GEP and drug transporters, in combination with chemotherapy, could provide novel treatment modalities to eradicate the aggressive hepatic tumor initiating cells.-
dc.languageengen_US
dc.publisherSpringer New York LLC. The Journal's web site is located at http://www.springer.com/west/home/medicine?SGWID=4-10054-70-173733513-0-
dc.relation.ispartofHepatology Internationalen_US
dc.rightsThe original publication is available at www.springerlink.com-
dc.titleGenomics approach to identify growth factor and drug transporter associated with liver cancer recurrence and chemo-resistanceen_US
dc.typeConference_Paperen_US
dc.identifier.emailCheung, ST: stcheung@hkucc.hku.hken_US
dc.identifier.emailCheung, PFY: cphyllis@hkucc.hku.hken_US
dc.identifier.emailCheng, CKC: ckccheng@hkucc.hku.hken_US
dc.identifier.emailFan, ST: stfan@hku.hken_US
dc.identifier.authorityCheung, ST=rp00457en_US
dc.identifier.authorityFan, ST=rp00355en_US
dc.identifier.doi10.1007/s12072-011-9330-7-
dc.identifier.hkuros211412en_US
dc.identifier.hkuros211293-
dc.identifier.volume6-
dc.identifier.issue1-
dc.identifier.spage26, abstract no. PS05-01-
dc.identifier.epage26, abstract no. PS05-01-
dc.identifier.isiWOS:000300362800001-
dc.publisher.placeUnited States-

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