Usefulness of staging systems and prognostic scores for hepatocellular carcinoma treatments

Adhoute, Xavier; Pénaranda, Guillaume; Raoul, Jean‐Luc; Treut, Patrice Le; Bollon, Emilie; Hardwigsen, Jean; Castellani, Paul; Perrier, H.; Bourlière, Marc

doi:10.4254/wjh.v8.i17.703

Cited by 29 publications

(20 citation statements)

References 64 publications

(82 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The presence of cirrhosis and portal vein hypertension makes the treatment and management of HCC a very complex process [27]. The anticancer properties of several traditional Chinese medicine-derived compounds have previously been studied and have been identified as promising candidates in the suppression of HCC metastasis [28].…”

Section: Discussionmentioning

confidence: 99%

Erinacine Facilitates the Opening of the Mitochondrial Permeability Transition Pore Through the Inhibition of the PI3K/ Akt/GSK-3β Signaling Pathway in Human Hepatocellular Carcinoma

Zhou

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Erinacine, which is extracted from the medicinal mushroom Hericium erinaceus, is known to play anticancer roles in human cancers. The following study aims to investigate the role of erinacine in the opening of the mitochondrial permeability transition pore (MPTP) in hepatocellular carcinoma (HCC) through the PI3K/Akt/GSK-3β signaling pathway and highlights the applicability of erinacine in HCC treatments. Methods: HCC and paracancerous tissues were obtained from 85 HCC patients who’ve undergone surgical resection. Immunohistochemistry was adopted to detect positive expression of PI3K, Akt, and GSK-3β. Treatment of HepG-2 with LY294002 (an inhibitor of the PI3K/Akt/GSK-3β signaling pathway) and different concentration of erinacine was performed to determine the involvement of LY294002 in erinacine action. The expressions of PI3K, Akt, GSK-3β, CyclinD1, Vimentin, β-catenin, Bcl-2, E-cadherin, Bax, and caspase-9 were determined by RT-qPCR and Western blot analysis. Cell viability, colony formation rate, migration, invasion, cycle, and apoptosis were detected by MTT, colony formation, wound healing assay, Transwell assay, and flow cytometry, respectively. The size and weight of xenograft tumors were observed in nude mice. Mitochondrial membrane potential in HepG-2 was determined using laser scanning confocal microscopy following JC-1 staining. Mitochondrial Ca²⁺ indicator Rhod-2, AM was used to detect the changes of mitochondrial Ca²⁺, while western blot analysis was employed to detect the presence levels of cytochrome C (cyt-C). Results: The results revealed that PI3K, Akt, and GSK-3β were up-regulated in HCC tissues. Erinacine or LY294002 led to a decrease in mitochondrial membrane potential, increase in intracellular mitochondrial Ca²⁺, and the release of cyt-C in mitochondria. In addition, Erinacine was found to decrease the mitochondrial membrane potential, expression of PI3K, Akt, GSK-3β, CyclinD1, Vimentin, β-catenin, and Bcl-2, cell proliferation, colony formation ability, migration, invasion, and xenograft tumor size, while E-cadherin, Bax, and caspase-9 expression, and cell apoptosis were elevated in a dose-dependent manner. Erinacine also stimulated the effects of LY294002 on the HCC. Following the addition of 500 μM Erinacine and MPTP opening inhibitor CsA, we found that the mitochondrial membrane potential level increased, while mitochondrial Ca2+ and Cyt-C decreased from the mitochondria. Conclusion: The results from the study demonstrated that erinacine induced MPTP opening, facilitates the release of cyt-C, and inhibited cell proliferation, migration, and invasion, while it promotes apoptosis by inactivating the PI3K/Akt/GSK-3β signaling pathway, preventing the progression of HCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Erinacine Facilitates the Opening of the Mitochondrial Permeability Transition Pore Through the Inhibition of the PI3K/ Akt/GSK-3β Signaling Pathway in Human Hepatocellular Carcinoma

Zhou

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Although not utilized in Europe and North America, the use of adjuvant TACE, following resection with curative intent, is common in mainland China, Hong Kong and Taiwan 13-15. However, the ability to establish the efficacy of adjuvant TACE has been met with mixed results in randomized control trials 16, 17. In addition, when TACE is performed in the palliative setting for unresectable patients, only a modest survival improvement is expected.…”

Section: Introductionmentioning

confidence: 99%

Gene signature predictive of hepatocellular carcinoma patient response to transarterial chemoembolization

Fako¹,

Martin²,

Pomyen³

et al. 2019

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Transarterial chemoembolization (TACE) is a commonly used treatment modality in hepatocellular carcinoma (HCC). The ability to identify patients who will respond to TACE represents an important clinical need, and tumor gene expression patterns may be associated with TACE response. We investigated whether tumor transcriptome is associated with TACE response in patients with HCC. We analyzed transcriptome data of treatment-naïve tumor tissues from a Chinese cohort of 191 HCC patients, including 105 patients who underwent TACE following resection with curative intent. We then developed a gene signature, TACE Navigator, which was associated with improved survival in patients that received either adjuvant or post-relapse TACE. To validate our findings, we applied our signature in a blinded manner to three independent cohorts comprising an additional 130 patients with diverse ethnic backgrounds enrolled in three different hospitals who received either adjuvant TACE or palliative TACE.TACE Navigator stratified patients into Responders and Non-Responders which was associated with improved survival following TACE in our test cohort (Responders: 67 months vs Non-Responders: 39.5 months, p<0.0001). In addition, multivariable Cox model demonstrates that TACE Navigator was independently associated with survival (HR: 9.31, 95% CI: 3.46-25.0, p<0.001). In our validation cohorts, the association between TACE Navigator and survival remained robust in both Asian patients who received adjuvant TACE (Hong Kong: 60 months vs 25.6 months p=0.007; Shandong: 61.3 months vs 32.1 months, p=0.027) and European patients who received TACE as primary therapy (Mainz: 60 months vs 41.5 months, p=0.041). These results indicate that a TACE-specific molecular classifier is robust in predicting TACE response. This gene signature can be used to identify patients who will have the greatest survival benefit after TACE treatment and enable personalized treatment modalities for patients with HCC.

show abstract

“…The benefits on survival of proposed treatment strategies at each different BCLC stage (except for stage D) have been documented in large studies that contributed to the construction and the straightforward diffusion of the BCLC system . Thus far, this approach has been considered the standard of care in Western world . However, BCLC recommendations derive from studies conducted in selected tertiary referral centers where technology and clinical expertise are outstanding.…”

Section: Introductionmentioning

confidence: 99%

Adherence to Barcelona Clinic Liver Cancer guidelines in field practice: Results of Progetto Epatocarcinoma Campania

Guarino

Tortora

Stefano

et al. 2018

J of Gastro and Hepatol

View full text Add to dashboard Cite

show abstract

Usefulness of staging systems and prognostic scores for hepatocellular carcinoma treatments

Cited by 29 publications

References 64 publications

Erinacine Facilitates the Opening of the Mitochondrial Permeability Transition Pore Through the Inhibition of the PI3K/ Akt/GSK-3β Signaling Pathway in Human Hepatocellular Carcinoma

Erinacine Facilitates the Opening of the Mitochondrial Permeability Transition Pore Through the Inhibition of the PI3K/ Akt/GSK-3β Signaling Pathway in Human Hepatocellular Carcinoma

Gene signature predictive of hepatocellular carcinoma patient response to transarterial chemoembolization

Adherence to Barcelona Clinic Liver Cancer guidelines in field practice: Results of Progetto Epatocarcinoma Campania

Contact Info

Product

Resources

About