Top

Published in:

01-09-2008 | Original Article

Apoptotic and inflammation markers in oral mucositis in head and neck cancer patients receiving radiotherapy: preliminary report

Authors: Arsinoi Xanthinaki, Ourania Nicolatou-Galitis, Pavlina Athanassiadou, Maria Gonidi, Vassilis Kouloulias, Anastasia Sotiropoulou-Lontou, George Pissakas, Konstantinos Kyprianou, John Kouvaris, Efstratios Patsouris

Published in: Supportive Care in Cancer | Issue 9/2008

Abstract

Goal of work

The aim of this study was to investigate the expression of pro-apoptotic protein p53 and anti-apoptotic proteins BCl-2 and MCl-1, as well as the expression of pro-inflammatory cytokines tumor necrosis factor (TNF) and interleukin-1beta (IL-1β) in patients developing mucositis during radiotherapy for head and neck cancer.

Materials and methods

Thirty-five patients receiving radiotherapy for head/neck cancer were included in this study. Patients were examined before radiotherapy. Oral mucositis was recorded weekly during radiotherapy. Cytologic smears from the oral cavity were taken with a brush. Immunocytochemical staining was performed by the use of p53, BCl-2, MCl-1 TNF and IL-1β monoclonal antibodies.

Main results

P53 was expressed in 1 of 15 smears before the initiation of radiotherapy (6.5%) compared to 3 of 7 smears from patients with grade III mucositis (43%) during radiotherapy. BCl-2 was expressed in 15 of 15 smears before radiotherapy (100%) and in three of seven patients with grade III mucositis (43%) during radiotherapy. MCl-1 was expressed in 10 of 14 samples before radiotherapy (71.5%) and in two of seven patients with grade III (28.5%) mucositis during radiotherapy. TNF was expressed in 9 of 14 patients before radiotherapy (64%) and in six of seven patients with grade III mucositis during radiotherapy (86%). IL-1β was detected in 7 of 14 patients before radiotherapy (50%) compared to 6 of 7 patients with grade III mucositis during radiotherapy (86%).

Conclusion

Our preliminary results indicate an induction of apoptosis and inflammation in the oral mucosa in patients developing mucositis during radiotherapy for head/neck cancer.

Adams J, Cory S (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281:1322–1326PubMedCrossRef

Aggarwal B, Kohr W, Hass P (1985) Human tumor necrosis factor. Production, puri®cation and characterization. J Biol Chem 260:2345–2354PubMed

Anilkumar T, Sarraf C, Hunt T, Alison M (1992) The nature of cytotoxic drug-induced cell death in murine intestinal crypts. Br J Cancer 65:552–558PubMed

Anthony L, Bowen J, Garden A, Hewson I, Sonis S (2006) New thoughts on the pathobiology of regimen-related mucosal injury. Support Care Cancer 14:516–518PubMedCrossRef

Baker S, Markowitz S, Fearon E, Willson J, Vogelstein B (1990) Suppression of human colorectal carcinoma cell growth by wild-type p53. Science 249:912–915PubMedCrossRef

Bellm L, Epstein J, Rose-Ped A (2000) Patient reports of complications of bone marrow transplantation. Support Care Cancer 8:33–39PubMed

Bianco J, Appelbaum F, Nemunaitis J (1991) Phase I–II trial of pentoxifylline for the prevention of transplant-related toxicities following bone marrow transplantation. Blood 78:1205–1211PubMed

Bowen J, Gibson R, Keefe D, Cummins A (2005) Cytotoxic chemotherapy upregulates pro-apoptotic Bax and Bak in the small intestine of rats and humans. Pathology 37:56–62PubMedCrossRef

Bowen J, Gibson R, Cummins A, Keefe D (2006) Intestinal mucositis: the role of the Bcl-2 family, p53 and caspases in chemotherapy-induced damage. Support Care Cancer 14:713–731PubMedCrossRef

10.

Bowen J, Gibson R, Cummins A, Tyskin A, Keefe D (2007) Irinotecan changes gene expression in the small intestine of the rat with breast cancer. Cancer Chemother Pharmacol 59:337–348PubMedCrossRef

11.

Carswell E, Old L, Kassel R (1975) An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A 72:3666–3670PubMedCrossRef

12.

Cox J, Stetz J, Pajak T (1995) Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 31:1341–1346PubMed

13.

Dinarello C (1996) Biologic basis for interleukin-1 in disease. Blood 87:2095–2147PubMed

14.

Dinarello C (2000) Proinflammatory cytokines. Chest 118:503–508PubMedCrossRef

15.

Elting L, Cooksley C, Chambers M (2003) The burdens of cancer therapy: clinical and economic outcomes of chemotherapy-induced mucositis. Cancer Nurs 98:153–159

16.

Ferra C, de Sanjose S, Lastra C (1997) Pentoxifylline, ciprofloxacin and prednisone failed to prevent transplantrelated toxicities in bone marrow transplant recipients and were associated with an increased incidence of infectious complications. Bone Marrow Transplant 20:1075–1080PubMedCrossRef

17.

Ferra C, de Sanjose S, Gallardo D (1998) IL-6 and IL-8 levels in plasma during hematopoietic progenitor transplantation. Haematologica 83:1082–1087PubMed

18.

Ferra C, de Sanjose S, Gallardo D, Berlanga JJ, Rueda F, Marin D, de la Banda E, Ancin I, Peris J, Garcia J, Granena A (1998) IL-6 and IL-8 levels in plasma during hematopoietic progenitor transplantation. Haematologica 83:1082–1087PubMed

19.

Ferrara J, Abhyankar S, Gilliland D (1993) Cytokine stem of graft-versus-host disease: a critical e€ector role for interleukin-1. Transplant Proc 25:1216–1217PubMed

20.

Gibson L, Fortney J, Magro G, Ericson S, Lynch J, Landreth K (1999) Regulation of BAX and BCL-2 expression in breast cancer cells by chemotherapy. Breast Cancer Res Treat 55:107–117PubMedCrossRef

21.

Gross A, McDonnell J, Korsmeyer S (1999) BCL-2 family members and the mitochondria in apoptosis. Genes Dev 13:1899–1911PubMedCrossRef

22.

Hall P, Benko H, Hogan K (1995) The influence of serum tumor necrosis factor-alpha and interleukin-6 concentrations or nonhematologic toxicities and hematologic recovery in patients with acute myelogenous leukemia. Exp Hematol 23:1256–1260PubMed

23.

Hehlgans T, Pfeffer K (2005) The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games. Immunology 115:1–20PubMedCrossRef

24.

Herr I, Debatin K (2001) Cellular stress response and apoptosis in cancer therapy. Blood 98:2603–2614PubMedCrossRef

25.

Hsu S, Raine L, Fanger H (1981) Use of avidin–biotin peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580PubMed

26.

Inomata A, Horii I, Suzuki K (2002) 5-Fluorouracil-induced intestinal toxicity: what determines the severity of damage to murine intestinal crypt epithelia. Toxicol Lett 133:231–240PubMedCrossRef

27.

Keefe D, Brealey J, Goland G, Cummins A (2000) Chemotherapy for cancer causes apoptosis that precedes hypoplasia in crypts of the small intestine in humans. Gut 47:632–637PubMedCrossRef

28.

Khan S, Wingard J (2001) Infection and mucosal injury in cancer treatment. J Natl Cancer Inst Monogr:31–36

29.

Kitada S, Krajewski S, Miyashita T, Krajewska M, Reed J (1996) Gamma-radiation induces upregulation of Bax protein and apoptosis in radiosensitive cells in vivo. Oncogene 12:187–192PubMed

30.

Krenger W, Ferrara J (1996) Graft-vs-host disease and the Th1/Th2 paradigm. Immunol Res 15:50–73PubMedCrossRef

31.

Leung L, Wang T (1999) Differential effects of chemotherapeutic agents on the Bcl-2/Bax apoptosis pathway in human breast cancer cell line MCF-7. Breast Cancer Res Treat 55:73–83PubMedCrossRef

32.

Lima V, Brito G, Cunha F (2005) Effects of the tumour necrosis factor-a inhibitors pentoxifylline and thalidomide in short-term experimental oral mucositis in hamsters. Eur J Oral Sci 113:210–217PubMedCrossRef

33.

Logan R, Stringer A, Bowen J, Yeoh A, Gibson R, Sonis S, Keefe D (2007) The role of pro-inflammatory cytokines in cancer treatment-induced alimentary tract mucositis: Pathobiology, animal models and cytotoxic drugs. Cancer Treat Rev 33(5):448–460 (May 14)PubMedCrossRef

34.

Lorenz H-M, Kalden J (2002) Perspectives for TNF-a-targeting therapies. Arthritis Res 4:S17–S24PubMedCrossRef

35.

Nicolatou-Galitis O, Dardoufas K, Markoulatos P (2001) Oral pseudomembranous candidiasis, herpes simplex virus-1 infection, and oral mucositis in head and neck cancer patients receiving radiotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwash. J Oral Pathol Med 30:471–480PubMedCrossRef

36.

Nicolatou-Galitis O, Athanassiadou P, Kouloulias V, Sotiropoulou-Lontou A, Dardoufas K, Polychronopoulou A, Gonidi M, Kyprianou K, Kolitsi G, Skarleas C, Pissakas G, Papanikolaou I, Kouvaris J (2006) Herpes simplex virus-1 (HSV-1) infection in radiation-induced oral mucositis. Support Care Cancer 14:753–762PubMedCrossRef

37.

Nicolatou-Galitis O, Velegraki A, Sotiropoulou-Lontou A (2006) Effect of fluconazole antifungal prophylaxis on oral mucositis in head and neck cancer patients receiving radiotherapy. Support Care Cancer 14(1):44–51PubMedCrossRef

38.

Nita M, Nagawa H, Tominaga O, Tsuno N, Fujii S, Sasaki S, Fu C, Takenoue T, Tsuruo T, Muto T (1998) 5-Fluorouracil induces apoptosis in human colon cancer cell lines with modulation of Bcl-2 family proteins. Br J Cancer 78:986–992PubMed

39.

Peterson DE, Schubert MM (2001) Oral toxicity. In: Perry MC (ed) The chemotherapy source book. 3rd edn. Lippincott, Williams and Wilkins, Philadelphia, pp 404–424

40.

Potten C, Wilson J, Booth C (1997) Regulation and significance of apoptosis in the stem cells of the gastrointestinal epithelium. Stem Cells 15:82–93PubMedCrossRef

41.

Rabinowitz J, Petros W, Stuart A, Peters W (1993) Characterization of endogenous cytokine concentrations after high-dose chemotherapy with autologous bone marrow support. Blood 81:2452–2459PubMed

42.

Remberger M, Ringdem O, Markling L (1995) TNF alpha levels are increased during bone marrow transplantation conditioning regimens in patients who develop acute GVHD. Bone Marrow Transplant 15:99–104PubMed

43.

Rose-Ped A, Bellm L, Epstein J (2002) Complications of radiation therapy for head and neck cancers: the patient’s perspective. Cancer Nurs 25:461–467PubMedCrossRef

44.

Sleijfer S, Vujaskovic Z, Limburg P, Koops H, Mulder N (1998) Induction of tumor necrosis factor-a as a cause of bleomycinrelated toxicity. Cancer Chemother Pharmacol 82:970–974

45.

Smith N, Rubenstein J, Eggener S, Kozlowski J (2003) The p53 tumor suppressor gene and nuclear protein: basic science review and relevance in the management of bladder cancer. J Urol 169:1219–1228PubMedCrossRef

46.

Sonis S (1998) Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatotoxicity. Oral Oncol 34:39–43PubMedCrossRef

47.

Sonis S (2004) A biological approach to mucositis. J Support Oncol 2:21–32PubMed

48.

Sonis S, Peterson R, Edwards L (2000) Defining mechanisms of action of interleukin-11 on the progression of radiation-induced mucositis in hamsters. Oral Oncol 36:393–381CrossRef

49.

Sonis S, Oster G, Fuchs H (2001) Oral mucositis and the clinical and economic outcomes of hematopoietic stem cell transplantation. J Clin Oncol 19:2201–2205PubMed

50.

Stiff P (2001) Mucositis associated with stem cell transplantation: current status and innovative approaches to management. Bone Marrow Transplant 17:S3–S11CrossRef

51.

Sutherland S, Browman G (2001) Prophylaxis of oral mucositis in irradiated head-and-neck cancer patients: a proposed classification scheme of interventions and metaanalysis of randomized controlled trials. Int J Radiat Oncol Biol Phys 49:917–930PubMedCrossRef

52.

Vousden K, Lu X (2002) Live or let die: the cell’s response to p53. Nat Rev Cancer 2:594–604PubMedCrossRef

53.

Xun C, Thompson J, Jennings C, Brown S, Widmerru B (1994) E€ect of total body irradiation, busulfan-cyclophosphamide or cyclophasphamide conditioning on in¯ammatory cytokine release and development of acute and chronic graft-vs-host disease in H-2-incompatible transplanted ScID mice. Blood 83:2360–2367PubMed

Title: Apoptotic and inflammation markers in oral mucositis in head and neck cancer patients receiving radiotherapy: preliminary report
Authors: Arsinoi Xanthinaki
Ourania Nicolatou-Galitis
Pavlina Athanassiadou
Maria Gonidi
Vassilis Kouloulias
Anastasia Sotiropoulou-Lontou
George Pissakas
Konstantinos Kyprianou
John Kouvaris
Efstratios Patsouris
Publication date: 01-09-2008
Publisher: Springer-Verlag
Published in: Supportive Care in Cancer / Issue 9/2008
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-007-0379-8

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Goal of work

Materials and methods

Main results

Conclusion

Please log in to get access to this content

Other articles of this Issue 9/2008

Birth and re-birth

Oral moxifloxacin or intravenous ceftriaxone for the treatment of low-risk neutropenic fever in cancer patients suitable for early hospital discharge

Patient–oncologist communication in advanced cancer: predictors of patient perception of prognosis

A systematic review of physical activity in prostate cancer survivors: outcomes, prevalence, and determinants

The use and toxicity of steroids in the management of patients with brain metastases

Changes in quality of life and its related factors in liver cancer patients receiving stereotactic radiation therapy

Keynote webinar | Spotlight on antibody–drug conjugates in cancer