Diagnostic Utility of Interleukin-6 (IL-6) for Primary Bile Duct Cancer and Changes in Serum IL-6 Levels Following Photodynamic Therapy

Cheon, Young Koog; Cho, Young Deok; Moon, Jong Ho; Jang, Jae Young; Kim, Young Seok; Kim, Yun Soo; Lee, Moon Sung; Lee, Joon Seong; Shim, Chan Sup

doi:10.1111/j.1572-0241.2007.01403.x

Cited by 95 publications

(53 citation statements)

References 14 publications

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“…The inflammatory cytokine IL-6 has been demonstrated to be frequently overexpressed in malignant neoplastic cells of human well differentiated intrahepatic cholangiocarcinomas [100] and to be increased in the serum and bile of cholangiocarcinoma patients [101][102][103] . IL-6 has been further shown to function as an autocrine growth factor for human cholangiocarcinoma cell lines [100,104,105] , and to up-regulate Mcl-1 in malignant human cholangiocyte cell lines [106,107] .…”

Section: Interleukin-6 (Il-6)/gp130mentioning

confidence: 99%

Role of ErbB family receptor tyrosine kinases in intrahepatic cholangiocarcinoma

Sirica¹

2008

WJG

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Aberrant expression and signaling of epidermal growth factor receptor (ErbB) family receptor tyrosine kinases, most notably that of ErbB2 and ErbB1, have been implicated in the molecular pathogenesis of intrahepatic cholangiocarcinoma. Constitutive overexpression of ErbB2 and/or ErbB1 in malignant cholangiocytes has raised interest in the possibility that agents which selectively target these receptors could potentially be effective in cholangiocarcinoma therapy. However, current experience with such ErbBdirected therapies have at best produced only modest responses in patients with biliary tract cancers. This review provides a comprehensive and critical analysis of both preclinical and clinical studies aimed at assessing the role of altered ErbB2 and/or ErbB1 expression, genetic modifications, and dysregulated signaling on cholangiocarcinoma development and progression. Specific limitations in experimental approaches that have been used to assess human cholangiocarcinoma specimens for ErbB2 and/or ErbB1 overexpression and gene amplification are discussed. In addition, current rodent models of intrahepatic cholangiocarcinogenesis associated with constitutive ErbB2 overexpression are reviewed. Select interactive relationships between ErbB2 or ErbB1 with other relevant molecular signaling pathways associated with intrahepatic cholangiocarcinoma development and progression are also detailed, including those linking ErbB receptors to bile acid, cyclooxygenase-2, i n t e r l e u k i n -6 / g p 1 3 0 , t ra n s m e m b ra n e m u c i n s , hepatocyte growth factor/Met, and vascular endothelial growth factor signaling. Lastly, various factors that can limit therapeutic efficacy of ErbB-targeted agents against cholangiocarcinoma are considered.

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Section: Interleukin-6 (Il-6)/gp130mentioning

confidence: 99%

Role of ErbB family receptor tyrosine kinases in intrahepatic cholangiocarcinoma

Sirica¹

2008

WJG

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“…The relationship between chronic inflammation and cancer has been well established [13]. Serum Il-6 was shown to be accurate diagnostic and prognostic marker in CCA, able to distinguish CCA from benign biliary disease [16]. Elevated serum concentration of Il-6 in patients with CCA declined rapidly after neoplasm resection [17] and after photodynamic therapy [39].…”

Section: Discussionmentioning

confidence: 99%

“…Overexpression of Il-6 was found in human malignant cholangiocytes and was linked to cell survival and tumor progression [12]. Elevated serum Il-6 levels were found in CCA discriminating CCA from benign biliary diseases [16]. In addition, serum Il-6 levels significantly dropped after CCA resection or its photodynamic destruction [17,18].…”

Section: Introductionmentioning

confidence: 99%

Serum and Bile Insulin-Like Growth Factor I, Interleukin-6 and Tumor M2- Pyruvate Kinase in Differentiation Malignant from Benign Biliary Strictures – Preliminary Report

Budzyńska¹,

Dulawa²

2016

Med chem (Los Angeles)

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Objective: To determine the value of serum and bile insulin-like growth factor I (IGF-I), interleukin-6 (Il-6) and tumor M2-pyruvate kinase (Tu M2-PK) in distinguishing pancreatobiliary cancers from benign biliary strictures.Material and methods: The study was performed prospectively on forty jaundiced patients admitted for biliary decompression due to bile duct strictures. Malignant strictures were diagnosed in 22 patients including 15 cases of CCA and 7 cases of pancreatic cancer, and benign biliary strictures in 18 cases. IGF-I, Il-6 and Tu M2-PK were measured in sera and bile by ELISA and compared to serum levels of carbohydrate antigens (CA) 19-9 and carcinoembryonic antigen (CEA).Results: Serum levels of IGF-I (74.4 vs. 117.0 ng/mL, p=0.03), Il-6 (37.1 vs. 17.0 pg/mL, p=0.04), CA19-9 (5689 vs. 38.9 U/mL, p<0.001) and CEA (27.5 vs. 1.9 ng/mL, p<0.0001) differed significantly between patients with malignant and benign biliary strictures, whereas biliary concentrations of IGF-I and Il-6 and serum and biliary levels of Tu M2-PK were comparable. Biliary IGF-I levels were significantly increased in pancreatic cancer as compared to cholangiocarcinoma and benign biliary strictures groups (966 vs. 137 ng/mL, p=0.03 and 966 vs. 90.6 ng/mL, p=0.01, respectively). The AUC-ROCs for serum IGF-I and serum Il-6 were 0.336 and 0.606, respectively, what was worse than that of CA 19-9 (0.855) and CEA (0.794).Conclusion: Measurement of serum IGF-I and Il-6 may be helpful in differentiation malignant from benign biliary strictures and biliary IGF-I seems to be a promising marker for distinguishing pancreatic cancer from cholangiocarcinoma and benign biliary occlusions.

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“…Le traitement peut être renouvelé tous les 3 à 6 mois, dépendant de la clinique et des habitudes des équipes. La nécrose cellulaire en elle-même libère de multiples cytokines qui génèrent une réponse immunitaire avec, notamment, la libération d'IL-6 qui apparaît comme une cytokine centrale dans la croissance tumorale du CC [7,8]. La PDT pourrait donc trouver, à travers la modulation de la production d'IL-6, l'une des explications à son efficacité dans cette indication (Fig.…”

Section: Les Résultatsunclassified

Photothérapie dynamique et cholangiocarcinome : où en est-on ?

Lecleire¹,

Delcenserie²

2012

Cancérodig.

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Le cholangiocarcinome non résécable reste grevé d'une mortalité très élevée avec une survie ne dépassant pas quelques mois. Cette mortalité est essentiellement due aux phénomènes septiques qui sont la conséquence de la cholestase chronique due à l'obstruction des voies biliaires. La priorité chez ces malades est donc de réaliser le meilleur drainage biliaire possible. Le traitement endoscopique ou radiologique palliatif par insertion de prothèse(s) biliaire(s) offre un bon drainage biliaire dont le bénéfice est souvent malheureusement transitoire, avec une réci-dive des symptômes au bout de quelques mois.La photothérapie dynamique (PDT) réalisée par voie endoscopique associée à l'insertion de prothèse(s) biliaire(s) représente une nouvelle alternative dont les résultats très encourageants méritent une attention toute particulière dans ce contexte où les résultats des traitements oncologiques classiques tels que la radiothérapie et la chimiothérapie restent décevants. Récemment, deux études randomisées et contrôlées ont montré un gain de survie significatif lorsque le drainage endoscopique par stent est associé à la PDT, passant de 3 à 7 mois à 16 à 21 mois de survie médiane. Ces bons résultats doivent maintenant être confirmés par de plus larges études randomisées, mais positionnent, d'ores et déjà, la PDT comme un « standard » à considérer dans le traitement palliatif du cholangiocarcinome non résécable. Mots-clésPhotothérapie dynamique, Cholangiocarcinome, Traitement palliatif ❚ AbstractUnresectable cholangicarcinoma is associated with a very high mortality, with an overall survival of only few months. This mortality is mainly due to chronic angiocholitis which is the consequence of the biliary tract obstruction. In these patients, priority must be given to the best biliary drainage to avoid septic complications. Endoscopic or radiologic biliary drainage by plastic or metallic stent offers a good biliary drainage but is unfortunately associated with a recurrence of symptoms within a few months.Photodynamic therapy (PDT) performed by endoscopy associated with the insertion of biliary stents is a new treatment yielding very good results, which deserve a very special attention in unresectable cholangiocarcinoma, given the disappointing results of classical oncologic treatments such as radiotherapy or chemotherapy. Recently, two randomized and controlled studies showed a significant benefit on overall survival when biliary drainage by stenting is associated with PDT, with an overall survival evaluated to 3-7 months vs 16-21 months. These good results must be confirmed by larger studies, but they already position PDT as a "standard" to be considered in the palliative treatment of unresectable cholangiocarcinoma.

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Diagnostic Utility of Interleukin-6 (IL-6) for Primary Bile Duct Cancer and Changes in Serum IL-6 Levels Following Photodynamic Therapy

Abstract: Serum IL-6 concentration is a useful addition to the available tests for the differential diagnosis of BDC, and serves as a marker for monitoring the response to treatment of BDC with PDT.

Cited by 95 publications

References 14 publications

Role of ErbB family receptor tyrosine kinases in intrahepatic cholangiocarcinoma

Role of ErbB family receptor tyrosine kinases in intrahepatic cholangiocarcinoma

Serum and Bile Insulin-Like Growth Factor I, Interleukin-6 and Tumor M2- Pyruvate Kinase in Differentiation Malignant from Benign Biliary Strictures – Preliminary Report

Photothérapie dynamique et cholangiocarcinome : où en est-on ?

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