Prognostic significance of Bcl-xL in human hepatocellular carcinoma

Watanabe, Jun; Kushihata, Fumiki; Honda, Kazuo; Sugita, Atsuro; Tateishi, Norihiko; Mominoki, Katsumi; Matsuda, Seiji; Kobayashi, Nobuaki

doi:10.1016/j.surg.2003.11.015

Cited by 94 publications

(63 citation statements)

References 25 publications

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“…Previous study showed that immunostaining of hepatocellular carcinoma lesions for Ki-67 was associated with higher mitotic activity. 24 Tumor size and Ki-67 expression have been found to be risk factors of early recurrence after surgical resection. 3 However, the associations identified between p53 and Ki-67 expression and hepatocellular carcinoma recurrence in liver transplant recipients is novel and could have important clinical implications if confirmed in prospective studies.…”

Section: Discussionmentioning

confidence: 99%

p53, Ki-67, and serum alpha feto-protein as predictors of hepatocellular carcinoma recurrence in liver transplant patients

et al. 2005

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Patients with hepatocellular carcinoma who undergo orthotopic liver transplantation (OLT) are at risk for posttransplant tumor recurrence. The aim of this study was to evaluate whether expression of p53 and Ki-67 in hepatocellular carcinoma lesions present in explanted liver tissue was associated with time to tumor recurrence after OLT. Subjects consisted of 20 consecutive patients who underwent OLT and were found to have hepatocellular carcinoma in the liver explant. Immunostaining for p53 and Ki-67 was performed by standard methods. The presence of nuclear immunostaining in 410% of the tumor tissue was considered positive. Time to recurrence of hepatocellular carcinoma after OLT was compared between patients with positive and negative immunostaining by the log rank test. Multivariate analysis was performed using a Cox regression model to control for potentially confounding clinical factors. Time to post-transplant hepatocellular carcinoma recurrence was significantly more rapid in p53 þ (P ¼ 0.0007) and Ki-67 þ cases (P ¼ 0.001). These associations remained significant in multivariate analysis. Furthermore, time to recurrent hepatocellular carcinoma was significantly shorter in patients with a serum alpha feto-protein (AFP) level Z100 ng/ml at time of diagnosis, compared to those with an AFP level o100 ng/ml (P ¼ 0.003). In conclusion, expression of p53 and Ki-67 in hepatocellular carcinoma lesions, and a serum AFP level Z100 ng/ml were associated with more rapid recurrence of hepatocellular carcinoma after OLT. Identification of patients at risk for early post-transplant recurrence could be used to guide surveillance and adjuvant treatment strategies.

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Section: Discussionmentioning

confidence: 99%

p53, Ki-67, and serum alpha feto-protein as predictors of hepatocellular carcinoma recurrence in liver transplant patients

et al. 2005

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“…The contribution of anti-apoptotic factors to hepatocarcinogenesis has been extensively studied [48][49][50] [53]; furthermore, its overexpression could independently predict a decreased overall-and disease-free survival [54,55]. Among the pro-apoptotic members of the Bcl-2 family, a down-regulation of the pro-apoptotic genes bax and bcl-Xs was observed in 80% and 64%, respectively, of HCCs [56,57].…”

Section: Molecular Pathways and Biological Functions Altered In Hepatmentioning

confidence: 99%

microRNA Involvement in Hepatocellular Carcinoma

Negrini

Gramantieri²,

Sabbioni³

et al. 2011

ACAMC

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“…[27][28] Especially, the absence of tumor-suppressor protein p53 and overexpression of anti-apoptosis proteins Bcl-2 and Bclx L play major roles in the formation of HCC and/or resistance to anticancer treatment. [29][30][31][32] The facts that Apoptin does not need a functional p53 pathway and apparently acts downstream of most decisive factors, 33 suggest that Asor-Apoptin will be applicable to a wide range of HCCs. Indeed, Apoptin induces apoptosis in vitro in actually all cancer cell types of a broad panel (470) that have been tested.…”

Section: Asor-apoptinmentioning

confidence: 99%

Inhibition of hepatocarcinoma by systemic delivery of Apoptin gene via the hepatic asialoglycoprotein receptor

Sun

et al. 2006

Cancer Gene Ther

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Specificity is a prerequisite for systemic gene therapy of hepatocarcinoma. In vitro, the tumor-specific viral death effector Apoptin selectively induces apoptosis in malignant hepatic cells. Intratumoral treatment of xenografted subcutaneous hepatomas with Apoptin results in tumor regression. Here, we report a systemic delivery vehicle containing the Apoptin gene linked to asialoglycoprotein (Asor), which targets asialoglycoprotein receptor (ASGPR) present only on the surface of hepatocytes. In vitro, the protein-DNA complex Asor-Apoptin induced apoptosis in HepG2 hepatocarcinoma cells but not in normal L-02 hepatocytes. Non-hepatocyte-derived tumorigenic human A549 cells lacking the membrane ASGPR were not affected by Asor-Apoptin. In vivo systemic delivery of Asor-Apoptin via the tail vein into mice bearing in situ hepatocarcinoma resulted in specific and efficient distribution of Apoptin in both hepatocarcinoma cells and normal hepatocytes. Five days after injection of Asor-Apoptin, the in situ hepatocarcinomas showed significant signs of regression, whereas the surrounding normal hepatocytes did not. Systemically delivered Asor-LacZ expressing non-apoptotic LacZ gene did not inhibit tumor growth. Our data reveal that systemic delivery of Asor-Apoptin specifically induces apoptosis in malignant hepatocytes and thus constitutes a powerful and safe therapeutics against hepatocarcinomas.

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Prognostic significance of Bcl-xL in human hepatocellular carcinoma

Cited by 94 publications

References 25 publications

p53, Ki-67, and serum alpha feto-protein as predictors of hepatocellular carcinoma recurrence in liver transplant patients

p53, Ki-67, and serum alpha feto-protein as predictors of hepatocellular carcinoma recurrence in liver transplant patients

microRNA Involvement in Hepatocellular Carcinoma

Inhibition of hepatocarcinoma by systemic delivery of Apoptin gene via the hepatic asialoglycoprotein receptor

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