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BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Drug sensitivity patterns of HHV8 carrying body cavity lymphoma cell lines

Authors: Rita Ötvös, Henriette Skribek, Lorand L Kis, Annunziata Gloghini, Laszlo Markasz, Emilie Flaberg, Staffan Eksborg, Jozsef Konya, Lajos Gergely, Antonino Carbone, Laszlo Szekely

Published in: BMC Cancer | Issue 1/2011

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Abstract

Background

Primary effusion lymphoma (PEL) is a rare KSHV/HHV8-associated high-grade non-Hodgkin's lymphoma (NHL) of B-cell origin, characterized by serous effusions in body cavities. Most patients are HIV-infected men with severe immunosuppression and other HHV8-associated diseases such as Kaposi's sarcoma (KS). The prognosis for those infected is poor, with a median survival of less than 6 months in most cohorts. Sustained complete remission is rare. High-dose chemotherapy regimens are used to improve remission rate and survival. The aim of the present study was to compare the drug sensitivity pattern of the available primary effusion (body cavity based) lymphoma-derived cell lines in order to find additional, potentially effective drugs that are not included in current chemotherapy treatment protocols.

Methods

We have analyzed 11 cell lines against 27 frequently used cytostatic drugs in short term (3 days) survival assays using automated high throughput confocal microscopy.

Results

All cell lines showed a distinct, individual drug sensitivity pattern. Considering the in vitro used and clinically achieved drug concentration, Vinorelbine, Paclitaxel, Epirubicin and Daunorubicin were the most effective drugs.

Conclusions

We suggest that inclusion of the above drugs into PEL chemotherapy protocols may be justified. The heterogeneity in the drug response pattern however indicated that assay-guided individualized therapy might be required to optimize therapeutic response.
Appendix
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Literature
1.
Carbone A, Gloghini A: KSHV/HHV8-associated lymphomas. Br J Haematol. 2008, 140 (1): 13-24.PubMed
2.
Boulanger E, Daniel MT, Agbalika F, Oksenhendler E: Combined chemotherapy including high-dose methotrexate in KSHV/HHV8-associated primary effusion lymphoma. Am J Hematol. 2003, 73 (3): 143-148.CrossRefPubMed
3.
Komanduri KV, Luce JA, McGrath MS, Herndier BG, Ng VL: The natural history and molecular heterogeneity of HIV-associated primary malignant lymphomatous effusions. J Acquir Immune Defic Syndr Hum Retrovirol. 1996, 13 (3): 215-226.CrossRefPubMed
4.
Morassut S, Vaccher E, Balestreri L, Gloghini A, Gaidano G, Volpe R, Tirelli U, Carbone A: HIV-associated human herpesvirus 8-positive primary lymphomatous effusions: radiologic findings in six patients. Radiology. 1997, 205 (2): 459-463.CrossRefPubMed
5.
Nador RG, Cesarman E, Chadburn A, Dawson DB, Ansari MQ, Sald J, Knowles DM: Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. Blood. 1996, 88 (2): 645-656.PubMed
6.
Ansari MQ, Dawson DB, Nador R, Rutherford C, Schneider NR, Latimer MJ, Picker L, Knowles DM, McKenna RW: Primary body cavity-based AIDS-related lymphomas. Am J Clin Pathol. 1996, 105 (2): 221-229.CrossRefPubMed
7.
Otsuki T, Kumar S, Ensoli B, Kingma DW, Yano T, Stetler-Stevenson M, Jaffe ES, Raffeld M: Detection of HHV-8/KSHV DNA sequences in AIDS-associated extranodal lymphoid malignancies. Leukemia. 1996, 10 (8): 1358-1362.PubMed
8.
Karcher DS, Alkan S: Human herpesvirus-8-associated body cavity-based lymphoma in human immunodeficiency virus-infected patients: a unique B-cell neoplasm. Hum Pathol. 1997, 28 (7): 801-808.CrossRefPubMed
9.
Valencia ME, Martinez P, Moreno V, Laguna F, Lahoz JG: AIDS-related body cavity-based lymphomas, herpesvirus-8 and HIV infection: a study of seven cases. Aids. 1999, 13 (18): 2603-2605.CrossRefPubMed
10.
Boulanger E, Agbalika F, Maarek O, Daniel MT, Grollet L, Molina JM, Sigaux F, Oksenhendler E: A clinical, molecular and cytogenetic study of 12 cases of human herpesvirus 8 associated primary effusion lymphoma in HIV-infected patients. Hematol J. 2001, 2 (3): 172-179.CrossRefPubMed
11.
12.
Halfdanarson TR, Markovic SN, Kalokhe U, Luppi M: A non-chemotherapy treatment of a primary effusion lymphoma: durable remission after intracavitary cidofovir in HIV negative PEL refractory to chemotherapy. Ann Oncol. 2006, 17 (12): 1849-1850.CrossRefPubMed
13.
An J, Sun Y, Fisher M, Rettig MB: Antitumor effects of bortezomib (PS-341) on primary effusion lymphomas. Leukemia. 2004, 18 (10): 1699-1704.CrossRefPubMed
14.
Flaberg E, Stuber G, Szekely L: Multi-dimensional laser confocal microscopy on live cells in submicroliter volumes using glass capillaries. Acta Histochem Cytochem. 2006, 39 (4): 103-106.CrossRefPubMedPubMedCentral
15.
Flaberg E, Sabelstrom P, Strandh C, Szekely L: Extended Field Laser Confocal Microscopy (EFLCM): combining automated Gigapixel image capture with in silico virtual microscopy. BMC Med Imaging. 2008, 8: 13-CrossRefPubMedPubMedCentral
16.
Markasz L, Kis LL, Stuber G, Flaberg E, Otvos R, Eksborg S, Skribek H, Olah E, Szekely L: Hodgkin-lymphoma-derived cells show high sensitivity to dactinomycin and paclitaxel. Leuk Lymphoma. 2007, 48 (9): 1835-1845.CrossRefPubMed
17.
Markasz L, Stuber G, Flaberg E, Jernberg AG, Eksborg S, Olah E, Skribek H, Szekely L: Cytotoxic drug sensitivity of Epstein-Barr virus transformed lymphoblastoid B-cells. BMC Cancer. 2006, 6: 265-CrossRefPubMedPubMedCentral
18.
Skribek H, Otvos R, Flaberg E, Nagy N, Markasz L, Eksborg S, Masszi T, Kozma A, Adam E, Miseta A, et al: Chronic lymphoid leukemia cells are highly sensitive to the combination of prednisolone and daunorubicin, but much less to doxorubicin or epirubicin. Exp Hematol. 2010, 38 (12): 1219-1230.CrossRefPubMed
19.
de Hoon MJ, Imoto S, Nolan J, Miyano S: Open source clustering software. Bioinformatics. 2004, 20 (9): 1453-1454.CrossRefPubMed
20.
Cersosimo RJ, Hong WK: Epirubicin: a review of the pharmacology, clinical activity, and adverse effects of an adriamycin analogue. J Clin Oncol. 1986, 4 (3): 425-439.PubMed
21.
Crews KR, Liu T, Rodriguez-Galindo C, Tan M, Meyer WH, Panetta JC, Link MP, Daw NC: High-dose methotrexate pharmacokinetics and outcome of children and young adults with osteosarcoma. Cancer. 2004, 100 (8): 1724-1733.CrossRefPubMed
22.
Albertioni F, Lindemalm S, Reichelova V, Pettersson B, Eriksson S, Juliusson G, Liliemark J: Pharmacokinetics of cladribine in plasma and its 5'-monophosphate and 5'-triphosphate in leukemic cells of patients with chronic lymphocytic leukemia. Clin Cancer Res. 1998, 4 (3): 653-658.PubMed
23.
Hersh MR, Kuhn JG, Phillips JL, Clark G, Ludden TM, Von Hoff DD: Pharmacokinetic study of fludarabine phosphate (NSC 312887). Cancer Chemother Pharmacol. 1986, 17 (3): 277-280.CrossRefPubMed
24.
Chan GL, Erdmann GR, Gruber SA, Stock P, Chen S, Ascher NL, Canafax DM: Pharmacokinetics of 6-thiouric acid and 6-mercaptopurine in renal allograft recipients after oral administration of azathioprine. Eur J Clin Pharmacol. 1989, 36 (3): 265-271.CrossRefPubMed
25.
Gruber A, Liliemark E, Tidefelt U, Paul C, Bjorkholm M, Peterson C, Liliemark J: Pharmacokinetics of mitoxantrone, etoposide and cytosine arabinoside in leukemic cells during treatment of acute myelogenous leukemia--relationship to treatment outcome and bone marrow toxicity. Leuk Res. 1995, 19 (10): 757-761.CrossRefPubMed
26.
Casale F, Canaparo R, Serpe L, Muntoni E, Pepa CD, Costa M, Mairone L, Zara GP, Fornari G, Eandi M: Plasma concentrations of 5-fluorouracil and its metabolites in colon cancer patients. Pharmacol Res. 2004, 50 (2): 173-179.CrossRefPubMed
27.
Fogli S, Danesi R, Gennari A, Donati S, Conte PF, Del Tacca M: Gemcitabine, epirubicin and paclitaxel: pharmacokinetic and pharmacodynamic interactions in advanced breast cancer. Ann Oncol. 2002, 13 (6): 919-927.CrossRefPubMed
28.
29.
Ghazal-Aswad S, Calvert AH, Newell DR: A single-sample assay for the estimation of the area under the free carboplatin plasma concentration versus time curve. Cancer Chemother Pharmacol. 1996, 37 (5): 429-434.CrossRefPubMed
30.
Graham MA, Lockwood GF, Greenslade D, Brienza S, Bayssas M, Gamelin E: Clinical pharmacokinetics of oxaliplatin: a critical review. Clin Cancer Res. 2000, 6 (4): 1205-1218.PubMed
31.
Rischin D, Ackland SP, Smith J, Garg MB, Clarke S, Millward MJ, Toner GC, Zalcberg J: Phase I and pharmacokinetic study of docetaxel in combination with epirubicin and cyclophosphamide in advanced cancer: dose escalation possible with granulocyte colony-stimulating factor, but not with prophylactic antibiotics. Ann Oncol. 2002, 13 (11): 1810-1818.CrossRefPubMed
32.
Bates SE, Bakke S, Kang M, Robey RW, Zhai S, Thambi P, Chen CC, Patil S, Smith T, Steinberg SM, et al: A phase I/II study of infusional vinblastine with the P-glycoprotein antagonist valspodar (PSC 833) in renal cell carcinoma. Clin Cancer Res. 2004, 10 (14): 4724-4733.CrossRefPubMed
33.
Desai ZR, Van den Berg HW, Bridges JM, Shanks RG: Can severe vincristine neurotoxicity be prevented?. Cancer Chemother Pharmacol. 1982, 8 (2): 211-214.CrossRefPubMed
34.
Freyer G, Delozier T, Lichinister M, Gedouin D, Bougnoux P, His P, Imadalou K, Trillet-Lenoir V: Phase II study of oral vinorelbine in first-line advanced breast cancer chemotherapy. J Clin Oncol. 2003, 21 (1): 35-40.PubMed
35.
Andersson B, Andersson I, Beran M, Ehrsson H, Eksborg S: Liquid chromatographic monitoring of daunorubicin and daunorubicinol in plasma from leukemic patients treated with daunorubicin or the daunorubicin-DNA complex. Cancer Chemother Pharmacol. 1979, 2 (1): 15-17.CrossRefPubMed
36.
Toffoli G, Corona G, Cattarossi G, Boiocchi M, Di Gennaro G, Tirelli U, Vaccher E: Effect of highly active antiretroviral therapy (HAART) on pharmacokinetics and pharmacodynamics of doxorubicin in patients with HIV-associated non-Hodgkin's lymphoma. Ann Oncol. 2004, 15 (12): 1805-1809.CrossRefPubMed
37.
Veal GJ, Cole M, Errington J, Parry A, Hale J, Pearson AD, Howe K, Chisholm JC, Beane C, Brennan B, et al: Pharmacokinetics of dactinomycin in a pediatric patient population: a United Kingdom Children's Cancer Study Group Study. Clin Cancer Res. 2005, 11 (16): 5893-5899.CrossRefPubMed
38.
Peng YM, Alberts DS, Chen HS, Mason N, Moon TE: Antitumour activity and plasma kinetics of bleomycin by continuous and intermittent administration. Br J Cancer. 1980, 41 (4): 644-647.CrossRefPubMedPubMedCentral
39.
Kozuch P, Hoff PM, Hess K, Adams J, Newman RA, Lee F, Pazdur R: Phase I bioequivalency study of MitoExtra and mitomycin C in patients with solid tumors. Cancer. 2001, 91 (4): 815-821.CrossRefPubMed
40.
Yan JH, Ataga K, Kaul S, Olson JS, Grasela DM, Gothelf S, Kutlar A, Orringer E: The influence of renal function on hydroxyurea pharmacokinetics in adults with sickle cell disease. J Clin Pharmacol. 2005, 45 (4): 434-445.CrossRefPubMed
41.
Gerrits CJ, Schellens JH, Burris H, Eckardt JR, Planting AS, van der Burg ME, Rodriguez GI, Loos WJ, van Beurden V, Hudson I, et al: A comparison of clinical pharmacodynamics of different administration schedules of oral topotecan (Hycamtin). Clin Cancer Res. 1999, 5 (1): 69-75.PubMed
42.
Ylikangas P, Mononen I: Serious neutropenia in ALL patients treated with L-asparaginase may be avoided by therapeutic monitoring of the enzyme activity in the circulation. Ther Drug Monit. 2002, 24 (4): 502-506.CrossRefPubMed
43.
Papandreou CN, Daliani DD, Nix D, Yang H, Madden T, Wang X, Pien CS, Millikan RE, Tu SM, Pagliaro L, et al: Phase I trial of the proteasome inhibitor bortezomib in patients with advanced solid tumors with observations in androgen-independent prostate cancer. J Clin Oncol. 2004, 22 (11): 2108-2121.CrossRefPubMed
44.
Penzak SR, Formentini E, Alfaro RM, Long M, Natarajan V, Kovacs J: Prednisolone pharmacokinetics in the presence and absence of ritonavir after oral prednisone administration to healthy volunteers. J Acquir Immune Defic Syndr. 2005, 40 (5): 573-580.CrossRefPubMed
Metadata
Title
Drug sensitivity patterns of HHV8 carrying body cavity lymphoma cell lines
Authors
Rita Ötvös
Henriette Skribek
Lorand L Kis
Annunziata Gloghini
Laszlo Markasz
Emilie Flaberg
Staffan Eksborg
Jozsef Konya
Lajos Gergely
Antonino Carbone
Laszlo Szekely
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-441

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