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      Low-Level Laser Therapy Stimulates Proliferation in Head and Neck Squamous Cell Carcinoma Cells

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          Objectives: Low-level laser therapy (LLLT) is a promising non-invasive treatment option for oropharyngeal mucositis, which is a common side effect of many oncological treatments. LLLT is known for its wound healing properties due to the stimulation of cellular processes, such as proliferation, migration and differentiation. Controversy exists on the possible stimulatory effect of LLLT on head and neck cancer (HNSCC) cells in patients treated with radiotherapy. The aim of this study was to evaluate the biostimulatory effect together with the underlying mechanisms of LLLT on HNSCC cancer cells and normal epithelial cells.

          Materials and methods: HNSCC cell lines (SCC154, SQD9, and SCC61) and human tonsil epithelial cells were exposed to a Gallium-Aluminum-Arsenide diode laser (830 nm, 150 mW) with energy densities of 0, 1, and 2 J/cm2. The proliferation potential of the cells was assessed by Sulforhodamine B assay, immunoblotting (mitogenic pathways), immunocytochemistry (Ki67), and flow cytometry (PI cell cycle staining).

          Results: Cell proliferation was increased in HNSCC cell lines after laser irradiation with 1 J/cm2, whereas no significant increase was seen after laser irradiation with 2 J/cm2. In contrast, no effect on cell proliferation was seen in the human tonsil epithelial cells after laser irradiation with any of the energy densities. The increased proliferation was associated with elevated levels of pAKT, pERK, and Ki67 protein expression and cell cycle progression.

          Conclusion: Our results show that LLLT increases cell proliferation in a dose-dependent manner in HNSCC cells but not in normal epithelial tonsil cells. These results suggest that LLLT has to be used with caution when treating oropharyngeal mucositis in HNSCC patients since tumor cells present in the LLLT irradiation field could be triggered by LLLT.

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          Most cited references 25

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          Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review.

          To determine the frequency of mucositis and associated outcomes in patients receiving radiotherapy (RT) for head and neck cancer through a systematic review of recently published literature. According to the study protocol, databases were searched for randomized clinical trials (English only, 1996-1999) of patients with head and neck cancer receiving RT with or without chemotherapy that reported one or more outcomes of interest. Thirty-three studies (n=6181 patients) met inclusion criteria. Mucositis was defined using a variety of scoring systems. The mean incidence was 80%. Over one-half of patients (56%) who received altered fractionation RT (RT-AF) experienced severe mucositis (grades 3-4) compared to 34% of patients who received conventional RT. Rates of hospitalization due to mucositis, reported in three studies (n=700), were 16% overall and 32% for RT-AF patients. Eleven percent of patients had RT regimens interrupted or modified because of mucositis in five studies (n=1267) reporting this outcome. Data insufficiency or heterogeneity prohibited analysis of mucositis severity and other associated outcomes, such as oral pain, dysphagia and opioid use. Mucositis is a frequent, severe toxicity in patients treated with RT for head and neck cancer. While it appears that mucositis may lead to hospitalization and treatment interruptions, its overall impact on outcomes has not been adequately investigated.
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            Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522.

            Combining cisplatin or cetuximab with radiation improves overall survival (OS) of patients with stage III or IV head and neck carcinoma (HNC). Cetuximab plus platinum regimens also increase OS in metastatic HNC. The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival (PFS).
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              Low-level laser therapy: a useful technique for enhancing the proliferation of various cultured cells.

              The aim of this work is to review the available literature on the details of low-level laser therapy (LLLT) use for the enhancement of the proliferation of various cultured cell lines including stem cells. A cell culture is one of the most useful techniques in science, particularly in the production of viral vaccines and hybrid cell lines. However, the growth rate of some of the much-needed mammalian cells is slow. LLLT can enhance the proliferation rate of various cell lines. Literature review from 1923 to 2010. By investigating the outcome of LLLT on cell cultures, many articles report that it produces higher rates of ATP, RNA, and DNA synthesis in stem cells and other cell lines. Thus, LLLT improves the proliferation of the cells without causing any cytotoxic effects. Mainly, helium neon and gallium-aluminum-arsenide (Ga-Al-As) lasers are used for LLLT on cultured cells. The results of LLLT also vary according to the applied energy density and wavelengths to which the target cells are subjected. This review suggests that an energy density value of 0.5 to 4.0 J/cm(2) and a visible spectrum ranging from 600 to 700 nm of LLLT are very helpful in enhancing the proliferation rate of various cell lines. With the appropriate use of LLLT, the proliferation rate of cultured cells, including stem cells, can be increased, which would be very useful in tissue engineering and regenerative medicine.

                Author and article information

                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                28 August 2018
                : 8
                1Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven Leuven, Belgium
                2Department of Radiation Oncology, Leuven Cancer Institute, University Hospitals Leuven , Leuven, Belgium
                Author notes

                Edited by: Jesper Grau Eriksen, Odense University Hospital, Denmark

                Reviewed by: Pavel Dulguerov, Geneva University Hospitals (HUG), Switzerland; Orlando Guntinas-Lichius, Universitätsklinikum Jena, Germany

                *Correspondence: Sandra Nuyts sandra.nuyts@

                This article was submitted to Head and Neck Cancer, a section of the journal Frontiers in Oncology

                Copyright © 2018 Bamps, Dok and Nuyts.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Figures: 4, Tables: 0, Equations: 0, References: 25, Pages: 6, Words: 4075
                Original Research


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