The Outcome of Sorafenib Therapy on Unresectable Hepatocellular Carcinoma: Experience of Conversion and Salvage Hepatectomy

Yoshimoto, Toshiaki; Imura, Satoru; Morine, Yuji; Ikemoto, Tetsuya; Arakawa, Yusuke; Iwahashi, Shuichi; Saito, Yu; Takasu, Chie; Ishikawa, Daichi; Teraoku, Hiroki; Bando, Yoshimi

doi:10.21873/anticanres.12250

Cited by 17 publications

(18 citation statements)

References 11 publications

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“…Although surgery is the main treatment for HCC, most patients have developed advanced HCC at the time of diagnosis due to the atypical symptoms in the early stages, missing the ideal operation time. For patients with unresectable advanced HCC, pharmacotherapy is the primary therapeutic strategy 2 . Nevertheless, due to drug resistance 3 and high rates of adverse side effects 4 , most conventional chemotherapeutic agents fail to produce satisfactory outcomes for HCC patients.…”

Section: Introductionmentioning

confidence: 99%

High throughput circRNA sequencing analysis reveals novel insights into the mechanism of nitidine chloride against hepatocellular carcinoma

et al. 2019

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Nitidine chloride (NC) has been demonstrated to have an anticancer effect in hepatocellular carcinoma (HCC). However, the mechanism of action of NC against HCC remains largely unclear. In this study, three pairs of NC-treated and NC-untreated HCC xenograft tumour tissues were collected for circRNA sequencing analysis. In total, 297 circRNAs were differently expressed between the two groups, with 188 upregulated and 109 downregulated, among which hsa_circ_0088364 and hsa_circ_0090049 were validated by real-time quantitative polymerase chain reaction. The in vitro experiments showed that the two circRNAs inhibited the malignant biological behaviour of HCC, suggesting that they may play important roles in the development of HCC. To elucidate whether the two circRNAs function as “miRNA sponges” in HCC, we identified circRNA-miRNA and miRNA-mRNA interactions by using the CircInteractome and miRwalk, respectively. Subsequently, 857 miRNA-associated differently expressed genes in HCC were selected for weighted gene co-expression network analysis. Module Eigengene turquoise with 423 genes was found to be significantly related to the survival time, pathology grade and TNM stage of HCC patients. Gene functional enrichment analysis showed that the 423 genes mainly functioned in DNA replication- and cell cycle-related biological processes and signalling cascades. Eighteen hubgenes (SMARCD1, CBX1, HCFC1, RBM12B, RCC2, NUP205, ECT2, PRIM2, RBM28, COPS7B, PRRC2A, GPR107, ANKRD52, TUBA1B, ATXN7L3, FUS, MCM8 and RACGAP1) associated with clinical outcomes of HCC patients were then identified. These findings showed that the crosstalk between hsa_circ_0088364 and hsa_circ_0090049 and their competing mRNAs may play important roles in HCC, providing interesting clues into the potential of circRNAs as therapeutic targets of NC in HCC.

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Section: Introductionmentioning

confidence: 99%

High throughput circRNA sequencing analysis reveals novel insights into the mechanism of nitidine chloride against hepatocellular carcinoma

et al. 2019

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“…However, due to the lack of specific symptoms, most HCCs are diagnosed at late/unresectable stage. For these patients, the multi-kinase inhibitors Sorafenib and Regorafenib provide very limited survival benefits [ 2 , 3 ]. Thus, there are major unmet medical needs for the treatment of HCC and elucidating the molecular mechanisms underlying HCC is of high importance to discover novel therapeutic approaches against this deadly disease.…”

Section: Introductionmentioning

confidence: 99%

Oncogenic potential of N-terminal deletion and S45Y mutant β-catenin in promoting hepatocellular carcinoma development in mice

Qiao

Tao

et al. 2018

BMC Cancer

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BackgroundHepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide with limited treatment options. Mutation of β-catenin is one of the most frequent genetic events along hepatocarcinogenesis. β-catenin mutations can be in the form of point mutation or large N-terminal deletion. Studies suggested that different β-catenin mutations might have distinct oncogenic potential.MethodsWe tested the oncogenic activity of β-cateninS45Y, one of the most frequent point mutations of β-catenin, and ∆N90-β-catenin, a form of β-catenin with a large N-terminal deletion, in promoting HCC development in mice. Thus, we co-expressed β-cateninS45Y or ∆N90-β-catenin together with c-Met into the mouse liver using hydrodynamic injection.ResultsWe found that both β-catenin mutations were able to induce HCC formation in combination with c-Met at the same latency and efficiency. Tumors showed similar histological features and proliferation rates. However, immunohistochemistry showed predominantly nuclear staining of β-catenin in c-Met/∆N90-β-catenin HCC, but membrane immunoreactivity in c-Met/β-cateninS45Y HCC. qRT-PCR analysis demonstrated that both ∆N90-β-catenin and β-cateninS45Y induced the same effectors, although at somewhat different levels. In cultured cells, both ∆N90-β-catenin and β-cateninS45Y were capable of inducing TCF/LEF reporter expression, promoting proliferation, and inhibiting apoptosis.ConclusionsOur study suggests that β-cateninS45Y and ∆N90-β-catenin, in combination with the c-Met proto-oncogene, have similar oncogenic potential. Furthermore, nuclear staining of β-catenin does not always characterize β-catenin activity.

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“…brivanib, nintedanib, and sorafenib) based on data from prospective randomized trials on HCC (8)(9)(10). Furthermore, if these drugs are effective, a greater choice of additional therapies, such as conversion hepatectomy, become available (11,12). According to these reports and the high response rate to lenvatinib, the purpose of systemic chemotherapy in unresectable HCC is changing from controlling disease to yielding favorable responses.…”

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confidence: 99%

Impact of Relative Dose Intensity of Early-phase Lenvatinib Treatment on Therapeutic Response in Hepatocellular Carcinoma

et al. 2019

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Background: Factors associated with response to lenvatinib have not been clarified in patients with hepatocellular carcinoma (HCC). Patients and Methods: This study retrospectively analyzed 50 patients treated with lenvatinib as first-line therapy between March 2018 and March 2019. Patients were divided into two groups by the Modified Response Evaluation Criteria in Solid Tumours (mRECIST) (responders and non-responders, whose best overall responses were complete (CR)/partial response (PR) and stable (SD)/progressive disease (PD), respectively). Factors associated with response were assessed, including the relative dose intensity 8 weeks after lenvatinib induction (8W-RDI). Results:The best overall responses were 0/22/14/14 of CR/PR/SD/PD. Multivariate analysis revealed that only 8W-RDI was significantly associated with response. The receiver operating characteristic curve for 8W-RDI in differentiating responders from non-responders revealed a cut-off value of 75%. Patients with 8W-RDI ≥75% experienced a higher response rate and longer progression-free survival than patients with 8W-RDI <75%. Conclusion: Our results suggest that maintaining an RDI ≥75% during the initial 8 weeks of lenvatinib treatment has a favorable impact on response.Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the second leading cause of cancer-related death, resulting in more than 700,000 deaths 5149

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The Outcome of Sorafenib Therapy on Unresectable Hepatocellular Carcinoma: Experience of Conversion and Salvage Hepatectomy

Abstract: Sorafenib combined with surgical resection is a feasible option in advanced HCC patients, if sorafenib has been effective.

Cited by 17 publications

References 11 publications

High throughput circRNA sequencing analysis reveals novel insights into the mechanism of nitidine chloride against hepatocellular carcinoma

High throughput circRNA sequencing analysis reveals novel insights into the mechanism of nitidine chloride against hepatocellular carcinoma

Oncogenic potential of N-terminal deletion and S45Y mutant β-catenin in promoting hepatocellular carcinoma development in mice

Impact of Relative Dose Intensity of Early-phase Lenvatinib Treatment on Therapeutic Response in Hepatocellular Carcinoma

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