EFFECT OF INTRATUMORAL INJECTION OF DOXORUBICIN IN THE TREATMENT OF INDUCED ORAL SQUAMOUS CELL CARCINOMA (EXPERIMENTAL STUDY) | ||||
Alexandria Dental Journal | ||||
Article 15, Volume 42, Issue 2, December 2017, Page 215-221 PDF (652.15 K) | ||||
Document Type: Original Article | ||||
DOI: 10.21608/adjalexu.2017.57930 | ||||
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Authors | ||||
Marwa M. Essawy* 1; Sahar M. El-Sheikh2; Hanaa S. Raslan3 | ||||
1Master in Oral Pathology, Oral Pathology Department Faculty of Dentistry, Alexandria University | ||||
2Professor of Oral Pathology, Oral Pathology Department, Faculty of Dentistry, Alexandria University | ||||
3- Professor of Oral Pathology, Oral Pathology Department, Faculty of Dentistry, Alexandria University | ||||
Abstract | ||||
INTRODUCTION: Oral squamous cell carcinoma (OSCC) is the sixth common cancer. Surgery remains the main way of OSCC treatment. It is followed by radiotherapy and chemotherapy either alone or in combination. Conventional chemotherapy is associated with systemic toxicity. Doxorubicin (DOX) is one of the effective chemotherapeutic drugs. Direct delivery of chemotherapeutics may reduce their side effects. OBJECTIVES: The study aimed to evaluate the anticancer effect of intratumoral injection of DOX in the treatment of chemically induced OSCC. MATERIALS AND METHODS: Thirty-two Syrian golden male hamsters were used as an animal model for oral carcinogenesis. After cancer induction, the hamsters were divided into 4 groups; saline-intraperitoneal (IP), saline-intratumoral, DOX-IP, and DOX-intratumoral. The clinical evaluation of the proposed treatment included measuring the change in tumor volume before and after treatment, whereas, the histological evaluation included calculating the apoptotic index. The proliferative activity was evaluated immunohistochemically by minichromosome maintenance 3 (MCM3). In all statistical results, a p < 0.05 was considered significant. RESULTS: The DOX-IP and DOX-intratumoral groups reported significant decrease in the mean tumor volume. The apoptotic index (AI) was significant only in the DOX-intratumoral group. The MCM3 immunostain showed significant decrease in the values of mean area percent (MA%) and mean optical density (MOD) in DOX-intratumoral group, whereas the DOX-IP group was insignificant in its MA% and MOD. CONCLUSION : Local delivery of this chemotherapeutic drug may be suitable alternative to the systemic administration, with superior anticancer effect in the treatment of superficial tumors | ||||
Keywords | ||||
Oral squamous cell carcinoma; Chemotherapy; Doxorubicin; Intratumoral; Hamsters; Minichromosome maintenance 3 | ||||
References | ||||
1. Ferlay J, Shin H-R, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J cancer 2010;127:2893–917.
2. Popat K, McQueen K, Feeley TW. The global burden of cancer. Best Pract Res Clin Anaesthesiol. 2013;27:399– 408.
3. Pereira MC, Oliveira DT, Landman G, Kowalski LP. Histologic subtypes of oral squamous cell carcinoma: prognostic relevance. J Can Dent Assoc. 2007;73:339–44.
4. Gasco M, Crook T. The p53 network in head and neck cancer. Oral Oncol 2003;39:222–31.
5. Feller L, Lemmer J. Oral Squamous Cell Carcinoma: Epidemiology, Clinical Presentation and Treatment. J Cancer Ther. 2012;3:263–8.
6. Ma J, Liu Y, Huang X-L, Zhang Z-Y, Myers JN, Neskey DM, et al. Induction chemotherapy decreases the rate of distant metastasis in patients with head and neck squamous cell carcinoma but does not improve survival or locoregional control: a meta-analysis. Oral Oncol. 2012;48:1076–84.
7. Logan RM. Advances in understanding of toxicities of treatment for head and neck cancer. Oral Oncol. 2009;45:844–8.
8. Shah JP, Gil Z. Current concepts in management of oral cancer - Surgery. Oral Oncol. 2009;45:394–401.
9. Thorn C, Oshiro C, Marsh S, Hernandez-Boussard T, McLeod H, Klein T, et al. Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenet Genomics. 2012;21:440–6.
10. Wang S, Konorev EA, Kotamraju S, Joseph J, Kalivendi S, Kalyanaraman B. Doxorubicin induces apoptosis in normal and tumor cells via distinctly different mechanisms: Intermediacy of H2O2- and p53-dependent pathways. J Biol Chem 2004;279:25535–43.
11. Parveen S, Misra R, Sahoo SK. Nanoparticles: A boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine Nanotechnology, Biol Med. 2012;8:147– 66.
12.Rivera MCA. 4NQO carcinogenesis: A model of oral squamous cell carcinoma. Int J Morphol. 2012;30:309– 14.
13. Kitakawa D, Cabral LAG, Marques MEA, Salvadori DMF, Ribeiro DA. Medium-term tongue carcinogenesis assays: A comparative study between 4-nitroquinoline 1- oxide (4NQO)-induced rat and dimethylbenzanthracene (DMBA)-induced hamster carcinogenesis. J Exp Anim Sci. 2006;43:219–27.
14. Keith WN, Mee PJ, Brown R. Response of Mouse Skin Tumors to Doxorubicin Is Dependent on Carcinogen Exposure. Cancer Res. 1990;50:6841–7.
15. Nelson JL, Roeder BL, Carmen JC, Roloff F, Pitt WG. Ultrasonically activated chemotherapeutic drug delivery in a rat model. Cancer Res. 2002;62:7280–3.
16. Afifi MM, El Sheikh SM, Abdelsalam MM, Ramadan H, Omar TA, El Tantawi M, et al. Therapeutic efficacy of plasmonic photothermal nanoparticles in hamster buccal pouch carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;115:743–51.
17.Cullen R, Maguire TM, McDermott EW, Hill ADK, O’Higgins NJ, Duffy MJ. Anti-apoptotic proteins, apoptotic and proliferative parameters and their prognostic significance in cervical carcinoma. Eur J Cancer. 2001;37:1104–10.
18. Okumura H, Natsugoe S, Nakashima S, Matsumoto M, Sakita H, Nakano S, et al. Apoptosis and cell proliferation in esophageal sqamous cell carcinoma treated by chemotherapy. Cancer Lett. 2000;158:211–6.
19. Myoung H, Kim MJ, Lee JH, Ok YJ, Paeng JY, Yun PY. Correlation of proliferative markers (Ki-67 and PCNA) with survival and lymph node metastasis in oral squamous cell carcinoma: a clinical and histopathological analysis of 113 patients. Int J Oral Maxillofac Surg. 2006;35:1005– 10.
20. Ashkavandi ZJ, Najvani AD, Tadbir AA, Pardis S, Ranjbar MA, Ashraf MJ. MCM3 as a novel diagnostic marker in benign and malignant salivary gland tumors. Asian Pac J Cancer Prev. 2013;14:3479–82.
21. Oliveira LR, Ribeiro-Silva A. Prognostic significance of immunohistochemical biomarkers in oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2011;40:298–307.
22. Kim S. Animal models of cancer in the head and neck region. Clin Exp Otorhinolaryngol. 2009;2:55–60.
23. Surkin MI, Schwartz SA, Markiewicz DA. Late-onset complications after chemoradiation for head and neck carcinomas. Ear, Nose Throat J. 2013;92:18-24.
24. Toscano N, Holtzclaw D, Hargitai I. Oral Implications of Cancer Chemotherapy. J Implant Adv Clin Dent. 2009;1:51–69.
25. Matsumura Y, Maeda H. A New Concept for Macromolecular Therapeutics in Cancer Chemotherapy: Mechanism of Tumoritropic Accumulation of Proteins and the Antitumor Agent Smancs. Cancer Res. 1986;46:6387–92.
26. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: A review. J Control Release. 2000;65:271–84.
27. Maeda H, Sawa T, Konno T. Mechanism of tumortargeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS. J Control Release. 2001;74:47–61.
28. Maeda H. The enhanced permeability and retention (EPR) effect in tumor vasculature: The key role of tumorselective macromolecular drug targeting. Adv Enzyme Regul. 2001;41:189–207.
29. Yu MK, Park J, Jon S. Targeting strategies for multifunctional nanoparticles in cancer imaging and therapy. Theranostics. 2012;2:3–44.
30. Hu Z, Garen A. Intratumoral injection of adenoviral vectors encoding tumor-targeted immunoconjugates for cancer immunotherapy. PNAS. 2000;97:9221–5.
31. Slos P, Meyer M De, Leroy P, Rousseau C, Acres B. Immunotherapy of established tumors in mice by intratumoral injection of an adenovirus vector harboring the human IL-2 cDNA: Induction of CD8 + T-cell immunity and NK activity. Cancer Gene Ther. 2001;8:321–32.
32. Dubrot J, Palazón A, Alfaro C, Azpilikueta A, Ochoa MC, Rouzaut A, et al. Intratumoral injection of interferon-α and systemic delivery of agonist anti-CD137 monoclonal antibodies synergize for immunotherapy. Int J Cancer 2011;128:105–18.
33. Sakagami H. Apoptosis-inducing activity and tumorspecificity of antitumor agents against oral squamous cell carcinoma. JDSR. 2010;46:173–87.
34. Zhang L, Yu SU, Duan Z, Wang Q, Tian GE, Tian YAN, et al. Treatment of liver cancer in mice by the intratumoral injection of an octreotide-based temperature ‑ sensitive gel. Int J Mol Med. 2014;33:117–27.
35. Shikanov A, Shikanov S, Vaisman B, Golenser J, Domb AJ. Cisplatin Tumor Biodistribution and Efficacy after Intratumoral Injection of a Biodegradable Extended Release Implant. Chemother Res Pract. 2011;2011:1–9.
36.Chen Y, Zhang W, Huang Y, Gao F, Fang X. In Vivo Biodistribution and Anti-Tumor Efficacy Evaluation of Doxorubicin and Paclitaxel-Loaded Pluronic Micelles Decorated with c ( RGDyK ) Peptide. PLoS One. 2016;11:1–18.
37. Kumar A, Zhang X, Liang X-J. Gold Nanoparticles: Emerging Paradigm for Targeted Drug Delivery System. Biotechnol Adv. 2013;31:593–606.
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