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CardioVascular and Interventional Radiology

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01-07-2009 | Laboratory Investigation

Impact of Rhenium-188, Gemcitabine, and 5-Fluorouracil on Cholangiocellular Carcinoma Cells: An In Vitro Study

Authors: Benjamin Wiesinger, Emese Farkas, Rainer Kehlbach, Rüdiger Bantleon, Matthias Werner, Jakub Wiskirchen

Published in: CardioVascular and Interventional Radiology | Issue 4/2009

Abstract

The purpose of this study was to compare the beneficial effects of radioactive stents and radioactive stents plus additional chemotherapy in the palliative treatment of cholangiocellular carcinomas. Cholangiocellular carcinoma cells (TFK-1 cells) were treated either with 8 Gy (RTB group) or 16 Gy (RTA group) ¹⁸⁸Re or with ¹⁸⁸Re irradiation (8 Gy) combined with either gemcitabine (8 Gy/Gem) or 5-fluorouracil (8 Gy/5-FU) at a dosage of 20 μg/ml medium for 4 days and subsequently compared with an untreated control group. Proliferation kinetics were assessed on days 4, 7, 11, 18, 25, and 32. Colony formation assays were performed on days 7, 18, and 32 and cell cycle distribution was examined on days 4, 7, 11, 15, 25, and 39. Cell proliferation kinetics showed the lowest cell numbers in the 8 Gy/5-FU group (control, 15,390,000; RTA group, 8,394,000; RTB group, 5,609,000; 8 Gy/Gem group, 423,000; and 8 Gy/5-FU group, 297,667). In contrast, clonogenic activity on day 32 was lower in the 8 Gy/Gem group (control, 29.3 colonies; RTB group, 23.1 colonies; 8 Gy/5-FU group, 21.5 colonies; 8 Gy/Gem, 3.3 colonies; and even augmented in the RTA group, with 37.7 colonies). Cell cycle distribution showed similar curves for all groups on slightly different levels except for the 8 Gy/5-FU group, which showed a relatively augmented percentage of cells on day 7 in the G2 M cycle phase and on day 4 in the S phase. In conclusion, irradiation (8 Gy) with ¹⁸⁸Re administered, e.g., via coated stents, combined with Gem could be a valid option for the treatment of CCCs.

Singhal D, van Gulik TM, Gouma DJ (2005) Palliative management of hilar cholangiocarcinoma. Surg Oncol 14(2):59–74PubMedCrossRef

Otto G (2007) Diagnostic and surgical approaches in hilar cholangiocarcinoma. Int J Colorectal Dis 22(2):101–108PubMedCrossRef

Mansfield SD, Barakat O, Charnley RM et al (2005) Management of hilar cholangiocarcinoma in the north of England: pathology, treatment, and outcome. World J Gastroenterol 11(48):7625–7630PubMed

Moff SL, Clark DP, Maitra A et al (2006) Utility of bile duct brushings for the early detection of cholangiocarcinoma in patients with primary sclerosing cholangitis. J Clin Gastroenterol 40(4):336–341PubMedCrossRef

Zeng ZC, Tang ZY, Fan J et al (2006) Consideration of the role of radiotherapy for unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 75 patients. Cancer J 12(2):113–122PubMed

Metz JM (2006) The role of radiation therapy in intrahepatic cholangiocarcinoma. Cancer J 12(2):102–104PubMed

Dingle BH, Rumble RB, Brouyers MC (2005) Cancer Care Ontario’s Program in Evidence-Based Care’s Gastrointestinal Cancer Disease Site Group. The role of gemcitabine in the treatment of cholangiocarcinoma and gallbladder cancer: a systematic review. Can J Gastroenterol 19(12):711–716PubMed

Akita H, Yamada T, Sasaki Y et al (2005) The evaluation of chemoradiotherapy to unresectable hepatobiliary cancers. Gan To Kagaku Ryoho 32(11):1727–1729PubMed

Stabin MG (1996) MIRDOSE: personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 37(3):538–546PubMed

10.

Kawrakow I, Fippel M, Friedrich K (1996) 3D electron dose calculation using a voxel based Monte Carlo algorithm (VMC). Med Phys 23(4):445–457PubMedCrossRef

11.

Han SL, Zhu GB, Yao JG et al (2005) Diagnosis and surgical treatment of primary hepatic cholangiocarcinoma. Hepatogastroenterology 52(62):348–351PubMed

12.

Kim HJ, Kim AY, Hong SS et al (2006) Biliary ductal evaluation of hilar cholangiocarcinoma: three-dimensional direct multi-detector row CT cholangiographic findings versus surgical and pathologic results—feasibility study. Radiology 238(1):300–308PubMedCrossRef

13.

Asayama Y, Yoshimitsu K, Irie H et al (2006) Delayed-phase dynamic CT enhancement as a prognostic factor for mass-forming intrahepatic cholangiocarcinoma. Radiology 238(1):150–155PubMedCrossRef

14.

Grimm J, Muller Hulsbeck S, Blume J et al (2001) Comparison of biphasic spiral CT and MnDPDP-enhanced MRI in the detection and characterization of liver lesions. Rofo 173(3):266–272PubMed

15.

Moff SL, Kamel IR, Eustace J et al (2006) Diagnosis of primary sclerosing cholangitis: a blinded comparative study using magnetic resonance cholangiography and endoscopic retrograde cholangiography. Gastrointest Endosc 64(2):219–223PubMedCrossRef

16.

Malhi H, Gores GJ (2006) Review article: the modern diagnosis and therapy of cholangiocarcinoma. Aliment Pharmacol Ther 23(9):1287–1296PubMedCrossRef

17.

Pawlik TM, Scoggins CR, Thomas MB et al (2004) Advances in the surgical management of liver malignancies. Cancer J 10(2):74–87 (Review)PubMedCrossRef

18.

He XS, Zhang S, Zhu XF et al (2006) Combined total hepatectomy, orthotopic liver transplantation and pancreatoduodenectomy for irresectable hilar bile duct carcinoma. Zhonghua Wai Ke Za Zhi 44(5):302–305PubMed

19.

Nissen NN, Cavazzoni E, Tran TT et al (2004) Emerging role of transplantation for primary liver cancers. Cancer J 10(2):88–96 (Review)PubMedCrossRef

20.

Parmar J, Marshall ES, Charters GA et al (2000) Radiation induced cell cycle delays and p53 status of early passage melanoma cell lines. Oncol Res 12(3):149–155PubMed

21.

Lee GW, Kang JH, Kim HG et al (2006) Combination chemotherapy with gemcitabine and cisplatin as first-line treatment for immunohistochemically proven cholangiocarcinoma. Am J Clin Oncol 29(2):127–131PubMedCrossRef

22.

Regine WF, Winter KA, Abrams RA et al (2008) Flourouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA 299(9):1019–1026PubMedCrossRef

23.

Akinci D, Akhan O, Ozkan F et al (2007) Palliation of malignant biliary and duodenal obstruction with combined metallic stenting. Cardiovasc Interv Radiol 30(6):1173–1177CrossRef

24.

Hatzidakis A, Krokidis M, Kalbakis K et al (2007) ePTFE/FEP-covered metallic stents for palliation of malignant biliary disease: can tumor ingrowth be prevented? Cardiovasc Interv Radiol 30(5):950–958CrossRef

25.

Brountzos EN, Ptochis N, Panagiotou I et al (2007) A survival analysis of patients with malignant biliary strictures treated by percutaneous metallic stenting. Cardiovasc Interv Radiol 30(1):66–73CrossRef

26.

Kozak Z, Ozkan H, Adli M et al (2005) Intraluminal brachytherapy with metallic stenting in the palliative treatment of malignant obstruction of the bile duct. Radiat Med 23(3):200–207

27.

Chen Y, Wang XL, Yan ZP et al (2004) HDR-192Ir intraluminal brachytherapy in treatment of malignant obstructive jaundice. World J Gastroenterol 10(23):3506–3510PubMed

28.

Kehlbach R, Dittmann H, Schmid T et al (2006) Early effects of rhenium-188 treatment on proliferation, migration, and matrix synthesis of cultured human aortic smooth muscle cells. Strahlenther Onkol 182(3):164–171PubMedCrossRef

29.

Albiero R, Nishida T, Adamian M et al (2000) Edge restenosis after implantation of high activity (³²P) radioactive beta-emitting stents. Circulation 101(21):2454–2457PubMed

30.

Ibrahim SM, Lewandowski RJ, Sato KT et al (2008) Radioembolization for the treatment of unresectable hepatocellular carcinoma: a clinical review. World J Gastroenterol 14(11):1664–1669PubMedCrossRef

31.

Freshney RI (2000) Plating efficiency. In: Culture of animal cells. Wiley-Liss, New York, pp 323–325

32.

Dittmann H, Dohmen BM, Kehlbach R et al (2002) Early changes in [¹⁸F] FLT uptake after chemotherapy: an experimental study. Eur J Nucl Med 29(11):1462–1469CrossRef

33.

Huether A, Höpfner M, Baradari V et al (2007) Sorafenib alone or as combination therapy for growth control of cholangiocarcinoma. Biochem Pharmacol 73(9):1308–1317PubMedCrossRef

Title: Impact of Rhenium-188, Gemcitabine, and 5-Fluorouracil on Cholangiocellular Carcinoma Cells: An In Vitro Study
Authors: Benjamin Wiesinger
Emese Farkas
Rainer Kehlbach
Rüdiger Bantleon
Matthias Werner
Jakub Wiskirchen
Publication date: 01-07-2009
Publisher: Springer-Verlag
Published in: CardioVascular and Interventional Radiology / Issue 4/2009
Print ISSN: 0174-1551
Electronic ISSN: 1432-086X
DOI: https://doi.org/10.1007/s00270-009-9563-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Impact of Rhenium-188, Gemcitabine, and 5-Fluorouracil on Cholangiocellular Carcinoma Cells: An In Vitro Study

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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