A Randomized Phase III Study of Doxorubicin Versus Cisplatin/Interferon α-2b/Doxorubicin/Fluorouracil (PIAF) Combination Chemotherapy for Unresectable Hepatocellular Carcinoma

Park, Yeon Hee; Mok, Tony; Zee, Benny; Leung, Thomas W.T.; Lai, Paul B.S.; Lau, Wan Yee; Koh, Jane; Mo, Frankie; Yu, Simon C.H.; Chan, Anthony T.C.; Hui, P. W.; Ma, Brigette; Lam, Kwok Chi; Ho, Wai–Kuen; Wong, Herman; Tang, Alan; Johnson, Philip J.

doi:10.1093/jnci/dji315

Cited by 547 publications

(412 citation statements)

References 30 publications

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“…Many small-scale trials of combining MTT with cytotoxic chemotherapy have been reported [385][386][387][388][389]. However, the treatment efficacy in terms of tumor response rate and patient survival were similar to those reported for the cytotoxic regimens alone (Table 3) [372,[375][376][377][378][379][380][381][382]. A second approach is to combine MTT targeting different molecular pathways.…”

Section: Future Directionsmentioning

confidence: 83%

“…Objective tumor response rate to single-agent cytotoxic therapies is usually less than 10%, and no survival benefit has been observed [372][373][374][375][376]. An earlier randomized trial comparing doxorubicin, 60-75 mg/m 2 every 3 weeks, with no treatment indicated a borderline improvement in overall survival (10.6 vs. 7.5 weeks) for patients who received doxorubicin [377].…”

Section: Cytotoxic Therapy: Single Agent and Combinationmentioning

confidence: 99%

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Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

et al. 2010

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Introduction The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on the management of hepatocellular carcinoma (HCC) in December 2008 to develop consensus recommendations. Methods The working party consisted of expert hepatologist, hepatobiliary surgeon, radiologist, and oncologist from Asian-Pacific region, who were requested to make drafts prior to the consensus meeting held at Bali, Indonesia on 4 December 2008. The quality of existing evidence and strength of recommendations were ranked from 1 (highest) to 5 (lowest) and from A (strongest) to D (weakest), respectively, according to the Oxford system of evidence-based approach for developing the consensus statements. 123Hepatol Int (2010) 4: 439-474 DOI 10.1007/s12072-010-9165-7 Results Participants of the consensus meeting assessed the quality of cited studies and assigned grades to the recommendation statements. Finalized recommendations were presented at the fourth APASL single topic conference on viral-related HCC at Bali, Indonesia and approved by the participants of the conference.

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Section: Future Directionsmentioning

confidence: 83%

Section: Cytotoxic Therapy: Single Agent and Combinationmentioning

confidence: 99%

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

et al. 2010

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“…By this time, the HCC xenografts reached the size of f100 mg. The dose of doxorubicin was f60% of the dose used in human [60 mg/m 2 or 1.6 mg/kg (12)]. Growth of established xenografts was monitored at least twice weekly, and tumor volume was calculated as described (31).…”

Section: Methodsmentioning

confidence: 99%

“…Recent large phase III studies have shown a 4% to 10.5% response rate in HCC treated with doxorubicin in the control group (11,12). Overall response rate, but not overall survival, was doubled when doxorubicin was given in combination with cisplatin, IFN, and 5-fluorouracil (12).…”

Section: Introductionmentioning

confidence: 99%

AZD6244 and doxorubicin induce growth suppression and apoptosis in mouse models of hepatocellular carcinoma

Huynh

Chow

Soo

2007

Molecular Cancer Therapeutics

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“…Hep3B cells (80% confluent) were exposed to 100 lM rosiglitazone for various times (3,8,12, or 24 hours). The PPARc/DNA binding activity in nuclear extract was measured using an enzyme-linked immunosorbent assay (ELISA)-based assay (Cayman Chemical, Ann Arbor, Mich).…”

Section: Pparc Binding Activity Assaymentioning

confidence: 99%

CITED2 is a novel direct effector of peroxisome proliferator‐activated receptor γ in suppressing hepatocellular carcinoma cell growth

Cheung

Zhao

Ying

et al. 2012

Cancer

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BACKGROUND: Previous reports from these authors found that activation of peroxisome proliferator-activated receptor gamma (PPARc) suppressed hepatocellular carcinoma (HCC). This study sought to identify the molecular target of PPARc and characterize its antitumor effect in HCC. METHODS: Optimal PPARc binding activity was obtained using the PPARc agonist rosiglitazone (100 lM) as determined by enzyme-linked immunosorbent assay. Under PPARc activation, 114 PPARc downstream targets associated with cancer development were identified by oligonucleotide microarray and Gene Ontology analysis. Among them, Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2 (CITED2) was the most prominent PPARc-bound target, as determined by chromatin immunoprecipitation-polymerase chain reaction. RESULTS: CITED2 messenger RNA and protein was significantly down-regulated in primary HCCs compared with their adjacent nontumor tissues. PPARc induced expression of CITED2 in HCC cell lines after adenovirus-PPARc transduction. The biological function of CITED2 was evaluated by loss-and gain-of-function assays. CITED2 knockdown in the hepatocyte cell line LO2 and HCC cell line Hep3B significantly increased cell viability and clonogenicity, and promoted G 1 -S phase transition in both cell lines. In contrast, ectopic expression of CITED2 in HepG2 and BEL7404 HCC cell lines significantly suppressed cell growth. The tumor suppressive effect of CITED2 was associated with up-regulation of cyclin-dependent kinase inhibitors p15 INK4B , p21 Wat1/Cip1 , p27 Kip1 , antiproliferative regulator interferon alpha 1, proapoptotic mediators including tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), TNFRSF25, caspase-8, granzyme A, and the tumor suppressor gene maspin. CITED2 was also associated with the down-regulation of cell cycle regulator cyclin D1, oncogene telomerase reverse transcriptase, and proinvasion/metastasis gene matrix metallopeptidase 2. CONCLUSIONS: CITED2 is a direct effector of PPARc for tumor suppression.

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A Randomized Phase III Study of Doxorubicin Versus Cisplatin/Interferon α-2b/Doxorubicin/Fluorouracil (PIAF) Combination Chemotherapy for Unresectable Hepatocellular Carcinoma

Cited by 547 publications

References 30 publications

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

AZD6244 and doxorubicin induce growth suppression and apoptosis in mouse models of hepatocellular carcinoma

CITED2 is a novel direct effector of peroxisome proliferator‐activated receptor γ in suppressing hepatocellular carcinoma cell growth

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