Cholangiocarcinoma: A compact review of the literature

Üstündağ, Yücel; Bayraktar, Yusuf

doi:10.3748/wjg.14.6458

Cited by 111 publications

(108 citation statements)

References 86 publications

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“…Although cholangiocarcinoma is a relatively rare hepatobiliary cancer, the incidence and mortality of cholangiocarcinoma have increased worldwide in recent years (1)(2)(3). In fact, intrahepatic cholangiocarcinoma is the second most common liver cancer, accounting for 10% to 15% of all primary liver malignancies (4).…”

Section: Introductionmentioning

confidence: 99%

ALDH1A3, the Major Aldehyde Dehydrogenase Isoform in Human Cholangiocarcinoma Cells, Affects Prognosis and Gemcitabine Resistance in Cholangiocarcinoma Patients

Chen

Weng

Cheng

et al. 2016

Clinical Cancer Research

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Purpose: Intrahepatic cholangiocarcinoma is a fatal primary liver cancer resulting from diagnosis at an advanced stage. Understanding the mechanisms of drug resistance and metastasis of cholangiocarcinoma may improve the disease prognosis. Enhanced aldehyde dehydrogenase (ALDH) activity is suggested to be associated with increased drug resistance and the metastasis. This study aims to investigate the roles of the ALDH isoforms in cholangiocarcinoma. Experimental Design: Aldefluor assays, RT-PCR, and Western blot analysis were used to identify the major ALDH isoforms contributing to Aldefluor activity in human cholangiocarcinoma cell lines. We manipulated isoform expression in HuCCT1 cells to elucidate the role of ALDH1A3 in the malignant progression of these cells. Finally, we used immunohistochemical staining to evaluate the clinical significance of ALDH1A3 in 77 hepatectomized cholangiocarcinoma patients and an additional 31 patients with advanced cholangiocarcinoma who received gemcitabine-based therapy. Results: ALDHhigh cholangiocarcinoma cells not only migrated faster but were more resistant to gemcitabine. Among the 19 ALDH isoforms studied, ALDH1A3 was found to be the main contributor to Aldefluor activity. In addition, we also found that knockdown of ALDH1A3 expression in HuCCT1 cells markedly reduced not only their sensitivity to gemcitabine, which might be attributed to a decreased expression of ribonucleotide reductase M1, but also their migration. Most importantly, this enzyme was also identified as an independent poor prognostic factor for patients with intrahepatic cholangiocarcinoma, as well as a prognostic biomarker of gemcitabine-treated patients. Conclusions: ALDH1A3 plays an important role in enhancing malignant behavior of cholangiocarcinoma and serves as a new therapeutic target. Clin Cancer Res; 22(16); 4225–35. ©2016 AACR.

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Section: Introductionmentioning

confidence: 99%

ALDH1A3, the Major Aldehyde Dehydrogenase Isoform in Human Cholangiocarcinoma Cells, Affects Prognosis and Gemcitabine Resistance in Cholangiocarcinoma Patients

Chen

Weng

Cheng

et al. 2016

Clinical Cancer Research

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“…Intrahepatic cholangiocarcinoma (ICC), the second most common primary hepatobiliary cancer globally, is a major cause of cancer-related deaths and shows no indication of a decrease in mortality rate (Khan et al, 2005;Ustundag and Bayraktar, 2008;Mosconi et al, 2009). Although the incidence of ICC had been primarily associated with developing countries, ICC is now increasing in developed countries, especially in the United Kingdom and Japan (Kato et al, 1990;TaylorRobinson et al, 1997;McLean and Patel, 2006;West et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Profiling of Intrahepatic Cholangiocarcinoma

Subrungruanga¹,

Thawornkunob²,

Chawalitchewinkoon-Petmitrc³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Intrahepatic cholangiocarcinoma (ICC) is ranked as one of the top five causes of cancer-related deaths. ICC in Thai patients is associated with infection with the liver fluke, Opisthorchis viverrini, but the molecular basis for development remains unclear. The present study employed a microarray approach to compare gene expression profiles of ICCs and normal liver tissues from the same patients residing in Northeast Thailand, a region with a high prevalence of liver fluke infection. In ICC samples, 2,821 and 1,361 genes were found to be significantly up-and down-regulated respectively (unpaired t-test, p<0.05; fold-change ≥2.0). For validation of the microarray results, 7 up-regulated genes (FXYD3, GPRC5A, CEACAM5, MUC13, EPCAM, TMC5, and EHF) and 3 downregulated genes (CPS1, TAT, and ITIH1) were selected for confirmation using quantitative RT-PCR, resulting in 100% agreement. The metallothionine heavy metal pathway contains the highest percentage of genes with statistically significant changes in expression. This study provides exon-level expression profiles in ICC that should be fruitful in identifying novel genetic markers for classifying and possibly early diagnosis of this highly fatal type of cholangiocarcinoma.

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“…8,9) Several epidemiological studies have shown that the incidence and mortality rates of CCA are increasing worldwide. [10][11][12] Biliary tract tumors remain a challenge to treat and manage due to their poor sensitivity to conventional therapies and discouraging treatment options. 13) In fact, radical surgery, the only effective treatment, is applicable in a minority of patients due to the common late clinical presentation and diagnosis of this tumor.…”

mentioning

confidence: 99%

Biliary Excretion of Curcumin Is Mediated by Multidrug Resistance-Associated Protein 2

Lee

2012

Biological & Pharmaceutical Bulletin

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Curcumin has a wide spectrum of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, and anticancer properties. Recently, its potential as effective chemoprevention against cholangiocarcinoma, a highly malignant tumor of the bile duct with limited therapeutic options, was reported. The purpose of the present study was to investigate the contribution of multidrug resistance-associated protein 2 (Mrp2) to the biliary excretion of curcumin using Sprague-Dawley rats (SDR) and Eisai hyperbilirubinemic rats (EHBR). After intravenous administration of curcumin with a loading dose of 4.5 mg/kg, followed by a constant infusion of 18 mg/kg/h to the SDR and EHBR, the pharmacokinetic parameters of curcumin were estimated. In EHBR, the total area under the bile concentration-time curve from 0 to 80 min following curcumin administration was dramatically decreased (0.094%) compared to that in SDR. In addition, the plasma-to-bile and liver-to-bile clearances were both significantly decreased compared to SDR. These results provide the first evidence that Mrp2 mediates the biliary excretion of curcumin and thus may be a major factor in the control of exposure of curcumin to the bile duct. This study may be helpful to the potential use of curcumin as a treatment for bile duct cancer, and to understanding the genetic polymorphism of Mrp2 for clinical trials of curcumin.

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Cholangiocarcinoma: A compact review of the literature

Cited by 111 publications

References 86 publications

ALDH1A3, the Major Aldehyde Dehydrogenase Isoform in Human Cholangiocarcinoma Cells, Affects Prognosis and Gemcitabine Resistance in Cholangiocarcinoma Patients

ALDH1A3, the Major Aldehyde Dehydrogenase Isoform in Human Cholangiocarcinoma Cells, Affects Prognosis and Gemcitabine Resistance in Cholangiocarcinoma Patients

Gene Expression Profiling of Intrahepatic Cholangiocarcinoma

Biliary Excretion of Curcumin Is Mediated by Multidrug Resistance-Associated Protein 2

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