Factors influencing distant recurrence of hepatocellular carcinoma following combined radiofrequency ablation and transarterial chemoembolization therapy in patients with hepatitis C

Nojiri, Shunsuke; Kusakabe,; Shinkai,; Matsuura,; Iio,; Miyaki,; Joh,

doi:10.2147/cmar.s22073

Cited by 12 publications

(9 citation statements)

References 21 publications

(27 reference statements)

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“…It has previously been reported to have direct growth inhibitory properties in vitro for breast cancer [15] and HCC [16] , and there is also suggestive clinical evidence for a suppressive effect on HCC in patients [17] . Several studies have shown a decrease in albumin levels in human HCC cells compared to the non-HCC liver [18][19][20] .…”

Section: Discussionmentioning

confidence: 98%

Role of Albumin in Growth Inhibition in Hepatocellular Carcinoma

et al. 2017

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Objective: Levels of serum albumin have recently emerged, together with C-reactive protein, as an important prognostic indicator for hepatocellular carcinoma (HCC). It has recently been reported that larger HCCs are associated with lower albumin levels. However, the albumin-mediated growth decrease has yet to be determined. Methods: We examined a large HCC cohort and then by direct exposure of HCC cells in vitro, the relationship of albumin levels to HCC growth. Results: We found that patients with lower albumin levels had significantly larger maximum tumor diameters, more portal vein thrombosis, more tumor multifocality, higher α-fetoprotein levels, and a lower survival than patients with higher albumin levels. Direct addition of exogenous albumin at physiological concentrations resulted in decreased growth in several HCC cell lines in vitro. We found a decrease in MAP kinase levels and in levels of Cdk2 and Cdk4, cyclinE, as well as in α-fetoprotein. Conclusion: These results indicate that in addition to its role as a monitor of systemic inflammation, albumin may have a direct role in HCC growth inhibition, either through modulation of α-fetoprotein or through its actions on growth-controlling kinases.

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Section: Discussionmentioning

confidence: 98%

Role of Albumin in Growth Inhibition in Hepatocellular Carcinoma

et al. 2017

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“…Additionally, albumin, as part of the ALBI grading system, has been shown to be a quantitative, useful and prognostic indicator of liver dysfunction in HCC patients (21)(22)(23)(24)(25). Albumin has previously been reported to have direct HCC growth inhibitory properties in vitro (26,27), and there is also suggestive clinical evidence for an inhibitory effect on HCC in patients (30)(31)(32). Several studies have also shown a decrease in albumin levels in human HCC cells compared with the non-HCC liver (33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

“…II) renders this explanation less likely. However, there is recent evidence suggesting an association between HCC growth and poorer liver function, except for albumin, which seems to be protective (27,(30)(31)(32). The mechanisms by which albumin might protect against HCC growth or damage are not yet clear, although there is some experimental evidence that albumin might directly suppress HCC growth (26,27), leading us to consider the possibility that in addition to its reflection of liver synthetic function and systemic inflammation, it might also have a direct tumor growth-modulating function in HCC patients.…”

Section: Discussionmentioning

confidence: 99%

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Serum Albumin Levels in Relation to Tumor Parameters in Hepatocellular Carcinoma Patients

Carr

Guerra

2017

Int J Biol Markers

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ORIGINAL RESEARCH ARTICLEFurthermore, albumin values have been used in the 2-parameter albumin-bilirubin (ALBI) quantitative grading system for liver function in HCC, which has in turn been incorporated into several staging systems (21-25). There is thus much recent interest in serum albumin levels in prognostication, mainly as a reflection of liver function in HCC. However, there is also some direct experimental evidence that increased albumin levels can actually suppress HCC cell growth (26,27). Viewed this way, albumin levels may influence prognosis as much by their actions on HCC biology as by their reflection of impaired liver function.In this study, we examined the clinical correlations of serum albumin levels in a large HCC patient cohort with parameters of HCC behavior, and found an inverse relationship between serum albumin levels and HCC aggressiveness. Methods Patient dataWe retrospectively analyzed a prospectively collected database of 4,139 HCC patients, as previously reported (28,29), who had full baseline tumor parameter data, including computed axial tomography (CT) scan information on HCC size, number of tumor nodules and presence of PVT and plasma AFP levels; complete blood counts; routine blood liver function tests (total bilirubin, γ-glutamyl transpeptidase [GGT] and albumin); and patient demographics. Database management conformed to legislation on privacy, and this study conformed to the ethical guidelines of the Declaration of Helsinki. Approval for this retrospective study

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“…It has been reported that oral BCAA may inhibit hepatocarcinogenesis [4]. We have revealed that a low recurrence rate of hepatocellular carcinoma (HCC) is associated with high serum albumin levels in patients [5]; therefore, high levels of serum albumin are a major indicator of a favorable outcome. However, the mechanism inhibiting the proliferation of HCC has not yet been elucidated, so we investigated the effect of serum albumin on HCC cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

885 Albumin Suppresses Human Hepatocellular Carcinoma Proliferation and the Cell Cycle

Nojiri¹,

Miyaki²,

Senda³

et al. 2010

Journal of Hepatology

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Many investigations have revealed that a low recurrence rate of hepatocellular carcinoma (HCC) is associated with high serum albumin levels in patients; therefore, high levels of serum albumin are a major indicator of a favorable prognosis. However, the mechanism inhibiting the proliferation of HCC has not yet been elucidated, so we investigated the effect of serum albumin on HCC cell proliferation. Hep3B was cultured in MEM with no serum or containing 5 g/dL human albumin. As control samples, Prionex was added to generate the same osmotic pressure as albumin. After 24-h incubation, the expressions of α-fetoprotein (AFP), p53, p21, and p57 were evaluated with real-time PCR using total RNA extracted from the liver. Protein expressions and the phosphorylation of Rb (retinoblastoma) were determined by Western blot analysis using total protein extracted from the liver. For flow cytometric analysis of the cell cycle, FACS analysis was performed. The percentages of cell cycle distribution were evaluated by PI staining, and all samples were analyzed employing FACScalibur (BD) with appropriate software (ModFit LT; BD). The cell proliferation assay was performed by counting cells with using a Scepter handy automated cell counter (Millipore). The mRNA levels of AFP relative to Alb(−): Alb(−), Alb(+), and Prionex, were 1, 0.7 ± 0.2 (p < 0.001 for Alb(−)), and 1 ± 0.3, respectively. The mRNA levels of p21 were 1, 1.58 ± 0.4 (p = 0.007 for Alb(−) and p = 0.004 for Prionex), and 0.8 ± 0.2, respectively. The mRNA levels of p57 were 1, 4.4 ± 1.4 (p = 0.002 for Alb(−) and Prionex), and 1.0 ± 0.1, respectively. The protein expression levels of Rb were similar in all culture media. The phosphorylation of P807/811 and P780 of Rb protein was reduced in Alb(+). More cells in the G0/G1 phase and fewer OPEN ACCESSInt. J. Mol. Sci. 2014, 15 5164 cells in S and G2/M phases were obtained in Alb(+) than in Alb(−) (G0/G1: 60.9%, 67.7%, 61.5%; G2/M: 16.5%, 13.1%, 15.6%; S: 22.6%, 19.2%, 23.0%, Alb(−), Alb(+), Prionex, respectively). The same results were obtained in HepG2. Cell proliferation was inhibited in 5 g/dL albumin medium in both HepG2 cells and Hep3B cells in 24 h culture by counting cell numbers. The presence of albumin in serum reduces the phosphorylation of Rb proteins and enhances the expression of p21 and p57, following an increase in the G0/G1 cell population, and suppresses cell proliferation. These results suggest that albumin itself suppresses the proliferation of hepatocellular carcinoma.

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Factors influencing distant recurrence of hepatocellular carcinoma following combined radiofrequency ablation and transarterial chemoembolization therapy in patients with hepatitis C

Cited by 12 publications

References 21 publications

Role of Albumin in Growth Inhibition in Hepatocellular Carcinoma

Role of Albumin in Growth Inhibition in Hepatocellular Carcinoma

Serum Albumin Levels in Relation to Tumor Parameters in Hepatocellular Carcinoma Patients

885 Albumin Suppresses Human Hepatocellular Carcinoma Proliferation and the Cell Cycle

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