Focus on hepatocellular carcinoma

Bruix, Jordi; Boix, Loreto; Sala, María; Llovet, Josep M.

doi:10.1016/s1535-6108(04)00058-3

Cited by 531 publications

(429 citation statements)

References 22 publications

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“…The cytokine, TRAIL, is considered a promising substance in the field of innovative cancer therapy because it is selectively cytotoxic to tumor cells while sparing normal cells [Walczak et al, 1999;Bruix et al, 2004]. However, various tumor cells, including HCC cells, are resistant to the apoptotic effects of TRAIL [Yamanaka et al, 2000;Pei et al, 2004;Kim et al, 2006].…”

Section: Discussionmentioning

confidence: 99%

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Quercetin sensitizes human hepatoma cells to TRAIL‐induced apoptosis via Sp1‐mediated DR5 up‐regulation and proteasome‐mediated c‐FLIP_S down‐regulation

Kim

Park

et al. 2008

J of Cellular Biochemistry

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This study demonstrates that combined treatment with subtoxic doses of quercetin (3 0 ,3 0 ,4 0 ,5,7-pentahydroxyflavone), a flavonoid found in many fruits and vegetables, plus tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces rapid apoptosis in TRAIL-resistant hepatocellular carcinoma (HCC) cells. Effective induction of apoptosis by the combined treatment with quercetin and TRAIL was not blocked by overexpression of Bcl-xL, which is known to confer resistance to various chemotherapeutic agents. These results suggest that this combined treatment may provide an attractive strategy for treating resistant HCCs. While the proteolytic processing of procaspase-3 by TRAIL was partially blocked in various HCC cells treated with TRAIL alone, co-treatment with quercetin efficiently recovered TRAIL-induced caspase activation. We found that quercetin treatment of HCC cells significantly up-regulated the mRNA and protein levels of DR5, a death receptor of TRAIL, in a transcription factor Sp1-dependent manner. Furthermore, treatment with quercetin significantly decreased the protein levels of c-FLIP, an inhibitor of caspase-8, through proteasome-mediated degradation. Finally, administration of small interfering RNA against DR5 or overexpression of c-FLIP S , but not c-FLIP L , significantly attenuated quercetin-stimulated TRAIL-induced apoptosis. Collectively, these findings show that quercetin recovers TRAIL sensitivity in various HCC cells via up-regulation of DR5 and down-regulation of c-FLIP S . J. Cell. Biochem. 105: 1386-1398. ß 2008 KEY WORDS: QUERCETIN; TRAIL; HEPATOMA; DR5; c-FLIP S H epatocellular carcinoma (HCC) is the fifth most frequent neoplasm worldwide (>500,000 death/year) [Bruix et al., 2004]. Most hepatocellular carcinoma patients are diagnosed at advanced stages that are unsuitable for the current curative therapies of resection and transplantation [Avila et al., 2006]. The current chemotherapeutic options yield poor responses and low patient survival, making them ineffective for treatment of advanced HCC [Avila et al., 2006]. Therefore, new therapeutic alternatives are needed for more effective treatment of this malignancy.Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF family, is considered a promising anticancer agent due to its ability to induce apoptosis in a variety of tumor cell types while having only negligible effects on normal cells [Ashkenazi et al., 1999]. Binding of TRAIL to either DR4 or DR5, two death receptors of TRAIL, leads to oligomerization and clustering of their intracellular death domains. The subsequent interaction of DR4 or DR5 with the adaptor molecule, FADD (Fas-associated death domain), via their respective death domains leads to recruitment and activation of caspase-8 [ Thomas et al., 2004]. Finally, caspase-8 activates the executioner caspases (e.g., caspase-3 and caspase-7), leading to apoptotic cell death [Srivastava, 2001]. Although TRAIL has garnered considerable attention as a novel anticancer agent...

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Section: Discussionmentioning

confidence: 99%

“…H epatocellular carcinoma (HCC) is the fifth most frequent neoplasm worldwide (>500,000 death/year) [Bruix et al, 2004]. Most hepatocellular carcinoma patients are diagnosed at advanced stages that are unsuitable for the current curative therapies of resection and transplantation [Avila et al, 2006].…”

mentioning

confidence: 99%

Quercetin sensitizes human hepatoma cells to TRAIL‐induced apoptosis via Sp1‐mediated DR5 up‐regulation and proteasome‐mediated c‐FLIP_S down‐regulation

Kim

Park

et al. 2008

J of Cellular Biochemistry

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“…Most cases of HCC are secondary to chronic liver diseases, such as hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, hepatic cirrhosis or primary biliary cholangitis 2, 3, 4. Approximately 80% of HCC are associated with chronic HBV infection 5. It has been proven that HBV can cause the immune attacks of liver due to the immune‐mediated mechanisms, leading to the development of hepatocyte inflammation, necrosis, proliferation, and finally oncogenic transformation 6.…”

Section: Introductionmentioning

confidence: 99%

T cell receptor repertoire profiling predicts the prognosis of HBV‐associated hepatocellular carcinoma

et al. 2018

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Tumor‐infiltrating T cell repertoire has been demonstrated to be closely associated with anti‐tumor immune response. However, the relationship between T cell repertoire in tumor tissue and prognosis has never been reported in Hepatocellular carcinoma (HCC). We performed the high‐throughput T cell receptor (TCR) sequencing to systematically characterize the infiltrating T cell repertoires of tumor and matched adjacent normal tissues from 23 HBV‐associated HCC patients. Significant differences on usage frequencies of some Vβ, Jβ, and Vβ‐Jβ paired genes have been found between the 2 groups of tissue samples, but no significant difference of TCR repertoire diversity could be found. Interestingly, the similarity of TCR repertoires between paired samples or the TNM stage alone could not be helpful to evaluate the prognosis of patients very well, but their combination could serve as an efficient prognostic indicator that the patients with early stage and high similarity showed a better prognosis. This is the first attempt to assess the potential value of TCR repertoire in HCC prognosis, and our findings could serve as a complement for the characterization of TCR repertoire in HCC.

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“…Although HCC is common in southeast Asia and subSahara Africa, the incidence rate of HCC has continued to increase in the United States and western Europe over the past 25 years, and the incidence and mortality rates of HCC are expected to double over the next 10-20 years (El Serag and Mason, 1999;Davila et al, 2004;El Serag, 2004). Although much is known about both the cellular changes that lead to HCC and the etiological agents (i.e., HBV, HCV infection and alcohol) responsible for the majority of HCC, the molecular pathogenesis of HCC is not well understood (Thorgeirsson and Grisham, 2002;Llovet et al, 2003;Bruix et al, 2004). Moreover, the severity of HCC, the lack of good diagnostic markers and treatment strategies, and clinical heterogeneity have rendered the disease a major challenge (Thorgeirsson and Grisham, 2002;Lee and Thorgeirsson, 2004).…”

Section: Introductionmentioning

confidence: 99%

Comparative and integrative functional genomics of HCC

2006

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Global gene expression profiling of hepatocellular carcinoma (HCC) is a promising new technology that has already refined the diagnosis and prognostic predictions of HCC patients. This has been accomplished by identifying genes whose expression pattern is associated with clinicopathological features of HCC tumors. Molecular characterization of HCC from gene expression profiling studies will undoubtedly improve the prediction of treatment responses, selection of treatments for specific molecular subtypes of HCC and ultimately the clinical outcome of HCC patients. The research focus is now shifting toward the identification of genetic determinants that are components of the specific regulatory pathways altered in cancers, and that may constitute novel therapeutic targets. Here we review the recent advances in gene expression profiling of HCC and discuss the future strategies for analysing large and complicated data sets from microarray studies and how to integrate these with diverse genomic data.

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Focus on hepatocellular carcinoma

Cited by 531 publications

References 22 publications

Quercetin sensitizes human hepatoma cells to TRAIL‐induced apoptosis via Sp1‐mediated DR5 up‐regulation and proteasome‐mediated c‐FLIP_S down‐regulation

Quercetin sensitizes human hepatoma cells to TRAIL‐induced apoptosis via Sp1‐mediated DR5 up‐regulation and proteasome‐mediated c‐FLIP_S down‐regulation

T cell receptor repertoire profiling predicts the prognosis of HBV‐associated hepatocellular carcinoma

Comparative and integrative functional genomics of HCC

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Focus on hepatocellular carcinoma

Cited by 531 publications

References 22 publications

Quercetin sensitizes human hepatoma cells to TRAIL‐induced apoptosis via Sp1‐mediated DR5 up‐regulation and proteasome‐mediated c‐FLIPS down‐regulation

Quercetin sensitizes human hepatoma cells to TRAIL‐induced apoptosis via Sp1‐mediated DR5 up‐regulation and proteasome‐mediated c‐FLIPS down‐regulation

T cell receptor repertoire profiling predicts the prognosis of HBV‐associated hepatocellular carcinoma

Comparative and integrative functional genomics of HCC

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Quercetin sensitizes human hepatoma cells to TRAIL‐induced apoptosis via Sp1‐mediated DR5 up‐regulation and proteasome‐mediated c‐FLIP_S down‐regulation

Quercetin sensitizes human hepatoma cells to TRAIL‐induced apoptosis via Sp1‐mediated DR5 up‐regulation and proteasome‐mediated c‐FLIP_S down‐regulation