Inhibitors of apoptosis proteins (IAPs) expression and their prognostic significance in hepatocellular carcinoma

Augello, Claudia; Caruso, Luca; Maggioni, Marco; Donadon, Matteo; Montorsi, Marco; Santambrogio, Roberto; Torzilli, Guido; Vaira, Valentina; Pellegrini, Caterina; Roncalli, Massimo; Coggi, Guido; Bòsari, Silvano

doi:10.1186/1471-2407-9-125

Cited by 132 publications

(115 citation statements)

References 36 publications

Supporting

Mentioning

106

Contrasting

Order By: Relevance

“…By contrast, survivin mRNA and protein were undetectable in adjacent paraneoplastic tissues (7). Studies by Yang et al (8), Zhu et al (9) and Hui et al (10) that used immunohistochemical staining, as well as studies by Chau et al (11) and Augello et al (12) that used RT-PCR analysis, confirmed the elevated levels of survivin in HCC tissues. These studies indicated that survivin protein was a promising histological tumor marker.…”

Section: Discussionsupporting

confidence: 59%

See 1 more Smart Citation

Survivin is not a promising serological maker for the diagnosis of hepatocellular carcinoma

et al. 2015

View full text Add to dashboard Cite

Abstract. Survivin expression in the serum of patients with hepatocellular carcinoma (HCC) and nonmalignant chronic liver diseases remain to be elucidated. The aims of the present study were to evaluate the diagnostic role of survivin in the serum of patients with HCC and identify which ELISA kit performed best in detecting the levels of serum survivin. In total, 80 patients were included in the present study, including 20 patients with HCC, 20 patients with liver cirrhosis, 20 patients with chronic hepatitis B virus infection and 20 healthy volunteers. The levels of survivin protein in the serum were detected using two different ELISA kits (R&D and Abnova). The positive ratios of serum survivin detected by the R&D ELISA kit in all the cases were 8.75% (7/80; median, 0 pg/ml; range, 0-39.8 pg/ml) and in HCC patients were 5% (1/20; median, 0 pg/ml; range, 0-39.8 pg/ml). For the same samples analyzed using the Abnova ELISA kit, the positive ratios of serum survivin in all the cases were 22.5% (18/80; median, 0 pg/ml; range, 0-553.5 pg/ml) and in HCC patients were 25% (5/20; median, 0 pg/ml; range, 0-93.5 pg/ml). The results obtained by the different ELISA kits demonstrated no statistically significant differences in the level of survivin between HCC patients and healthy controls. The correlation coefficient was 0.0064 (P= 0.481) when analyzing the same serum samples with the different ELISA kits. In addition, the highest positive ratio of serum survivin was observed using the Abnova kit. A statistically significant difference in the results was observed between the R&D and Abnova kits. In general, the levels and positive ratios of serum survivin in the patients with HCC were significantly low. Furthermore, no difference was observed between HCC patients and controls in regard to the levels of serum survivin detected by the R&D and Abnova ELISA kits. In conclusion, survivin is unlikely to be a promising serological maker for the diagnosis of HCC. IntroductionHepatocellular carcinoma (HCC) is the sixth most common malignant neoplasm and the third most common cause of cancer-associated mortalities worldwide (1,2). At present, the combination of α-fetoprotein (AFP) with ultrasonography or computed tomography (CT) is widely used in clinical practice for the early diagnosis of HCC. However, a previous study identified that the sensitivity of AFP was only 25-65%. In addition, a number of patients with chronic hepatitis, liver cirrhosis and other liver diseases or gastrointestinal cancers have been found to exhibit elevated levels of AFP (3). Therefore, identifying novel and promising makers that may improve the diagnostic accuracy of HCC is required. Survivin, also known as baculoviral inhibitor of apoptosis repeat containing 5 (BIRC 5), is an inhibition of apoptosis protein. It was initially separated by researchers from Yale University, and has since been identified to be involved in the inhibition of apoptosis (4) and the regulation of mitosis (5).Previous studies have revealed that survivin is highly expressed in the...

show abstract

Section: Discussionsupporting

confidence: 59%

“…By contrast, survivin mRNA and protein were undetectable in adjacent paraneoplastic tissues (7). Since then, a number of studies have also identified an elevation in the level of survivin in HCC tissues using immunohistochemical staining (8-10) and 12). These findings indicate the potential value of survivin in the diagnosis of HCC.…”

Section: Introductionmentioning

confidence: 87%

Survivin is not a promising serological maker for the diagnosis of hepatocellular carcinoma

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Increased survivin expression in cancer patients is an unfavorable prognostic marker correlating with decreased overall survival in several malignancies, including lung (33,34), gastric (35), colorectal (18), and breast carcinomas (14), hepatocellular carcinoma (36) as well as in pediatric solid tumors such as neuroblastoma (37), and hepatoblastoma (23). Relationship between survivin expression and RMS are still unknown.…”

Section: Discussionmentioning

confidence: 99%

Survivin selective inhibitor YM155 promotes cisplatin-induced apoptosis in embryonal rhabdomyosarcoma

Ueno

Uehara

Nakahata

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Survivin, a member of the inhibitor of apoptosis protein family, functions as a key regulator of programmed cell death. YM155 is a small molecule that selectively inhibits survivin. We investigated the effect of YM155 on survivin suppression in the human rhabdomyosarcoma (RMS) cell line RD. The efficacy of YM155 in combination with cisplatin was also determined in a xenograft model. The effect of YM155 on survivin expression in the RD cell line was examined at both mRNA and protein levels using real-time PCR and western blot analysis. RD cells were cultured with various concentrations of YM155, then cisplatin was added to the medium and the anti-proliferation response was determined. Cell growth was evaluated by WST-8 assay. Finally, the efficacy of YM155 combined with cisplatin was examined in an established xenograft model. Survivin mRNA levels in the RD cell line were decreased to 72 and 24% at 24 and 48 h, respectively, after 10 nM of YM155 was added. YM155 also decreased the levels of survivin protein. YM155 treatment (10 nM) inhibited cell proliferation of RD in a dose-dependent manner in vitro, with 58% of cells viable at 48 h. When cultured with 10 nM of YM155 and 10 µM cisplatin, RD cells demonstrated only 25% of the growth observed when cultured with cisplatin alone. YM155 in combination with cisplatin significantly inhibited tumor growth by 13% compared with control (P<0.0001) in RD xenograft tumors. YM155 increased the sensitivity of cisplatin by suppressing survivin in the embryonal RMS cell line RD. Further studies should investigate the use of YM155 as an apoptosis inducer, either alone or in combination with cisplatin, for the treatment of malignant RMS.

show abstract

“…Several investigators have reported livin expression in fetal and some tumor cell lines and primary tumors (Augello et al, 2009;Dasgupta et al, 2010;El-Mesallamy et al, 2011). Kasof and Gomes (2001) reported high expression of the α-isoform in several melanoma cell lines and primary melanoma tumors.…”

Section: Introductionmentioning

confidence: 99%

Effect of RNAi-mediated silencing of Livin gene on biological properties of colon cancer cell line LoVo

Zou¹,

Wang²,

Zhu³

et al. 2014

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. This study aimed to investigate the effect of RNAimediated silencing of the Livin gene on biological properties of the colon cancer cell line LoVo. Interference vectors pSilencer4.1-Ll and pSilencer4.1-L2 targeting the Livin gene were constructed and transfected into LoVo cells. The expression of the Livin gene was determined by RT-PCR and Western blotting. The apoptosis, cell cycle, colony formation, proliferation of LoVo cells, as well as their sensitivity to cisplatin, were detected by flow cytometry, colony formation assay and MTT. Livin mRNA and protein expression in LoVo cells could be effectively silenced by pSilencer4.1-Ll but not pSilencer4.1-L2. In the pSilencer4.1-Ll transfection group, the apoptosis rate of LoVo cells was significantly higher than in the control group (24.2 ± 3.2 vs 8.1 ± 1.4%, P < 0.01), and after 72 h, cell proliferation was clearly decreased (about 70% inhibition). Compared with the control group, the colony formation rate in pSilencer4.1-Ll transfection group was obviously decreased (15 RNAi-mediated Livin gene silencing in LoVo cells ± 4.6 vs 85 ± 5.8%, P < 0.01), with increased proportion of S phase cells (45.7 ± 4.9 vs 28.0 ± 3.0%, P < 0.01), decreased proportion of G1 phase cells (43.0 ± 5.2 vs 62.8 ± 5.1%, P < 0.01), and increased sensitivity to cisplatin (apoptosis rate increased from 43.4 ± 6.9 to 65.3 ± 6.2%, P < 0.01). pSilencer4.1-Ll can effectively silence Livin gene expression in LoVo colon cancer cells, inhibit cell proliferation and colony formation, induce apoptosis, and enhance sensitivity to cisplatin.

show abstract

Inhibitors of apoptosis proteins (IAPs) expression and their prognostic significance in hepatocellular carcinoma

Cited by 132 publications

References 36 publications

Survivin is not a promising serological maker for the diagnosis of hepatocellular carcinoma

Survivin is not a promising serological maker for the diagnosis of hepatocellular carcinoma

Survivin selective inhibitor YM155 promotes cisplatin-induced apoptosis in embryonal rhabdomyosarcoma

Effect of RNAi-mediated silencing of Livin gene on biological properties of colon cancer cell line LoVo

Contact Info

Product

Resources

About