The Effect of Photobiomodulation on Nitrite and Inflammatory Activity in Radiotherapy-Induced Oral Mucositis: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: To investigate pro- and anti-inflammatory cytokines and nitrite salivary levels in patients with head and neck cancer receiving photobiomodulation therapy (PBMT) associated with a Preventive Oral Care Program (POCP), for prevention and control of oral mucositis (OM) during radiotherapy (RT) associated or not with chemotherapy protocol. STUDY DESIGN/MATERIALS AND METHODS: In this randomized double-blinded clinical trial, 48 patients were randomly assigned to two groups: PBMT (n = 25) and Control (n = 23). In the PBMT group, patients were submitted to PBMT associated with the POCP. In the Control group, patients were submitted only to the POCP. Saliva samples were collected in the 1st (baseline), 7th, 14th, 21st, and 30th sessions of RT, and the levels of interleukin-6 (IL-6), IL-8, IL-10, IL-12p70, IL-1ß, and tumoral necrosis factor-α (TNF-α) were measured using the cytometric bead array. Nitrite levels were measured by colorimetric method. OM was assessed using the World Health Organization and the National Cancer Institute scales. RESULTS: Patients in the PBMT group presented less severe OM. PBMT tended to stabilize nitrite concentration levels during the RT regimen. The IL-1ß concentration was associated with higher OM scores. PBMT promoted an increase in IL-12p70, TNF-α, and IL-10 concentration. CONCLUSION: PBMT was effective in the prevention and control of severe OM, and its mechanism of action may be related to a better balance of inflammatory response that may favor injury control. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Effect of low-level laser therapy on chemoradiotherapy-induced oral mucositis and salivary inflammatory mediators in head and neck cancer patients.

BACKGROUND AND OBJECTIVE: Oral mucositis (OM) is considered a painful and debilitating side effect in patients receiving head and neck cancer treatment. Low-level laser therapy (LLLT) proved to be effective to prevent and treat chemoradiotherapy-induced OM. The aim of this study was to evaluate the effect of LLLT in the severity of OM in patients with head and neck cancer and on the release of salivary inflammatory mediators. Clinical (score of OM severity) and biochemical parameters (concentration of inflammatory mediators, growth factors, and enzymes in saliva) were used. MATERIALS AND METHODS: Thirty patients were randomized into two groups: control and laser. LLLT was performed three times a week in the laser group, while control group received sham irradiation. OM severity was assessed according to the World Health Organization (WHO) and National Cancer Institute (NCI) scales. Pro-inflammatory and anti-inflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-10, TGF-ß), growth factors (EGF, FGF, VEGF), and metalloproteinases (MMP2/TIMP2, MMP9/TIMP2) concentrations were assessed using ELISA test. Saliva samples were collected on admission, and at the 7th, 21st, and 35th sessions of radiotherapy. RESULTS: The laser group showed a reduction in the severity of OM, which coursed with significantly diminished salivary concentration of EGF and VEGF in the 7th radiotherapy session and of IL-6 and FGF in the 35th. There was a trend for reduced levels of IL-1ß, TNF-α, IL-10, TGF-ß, MMP2/TIMP2, MMP9/TIMP2 in the laser group compared to the control, however, no statistically significant differences were found. CONCLUSIONS: These findings demonstrated that LLLT was effective in reducing the severity of chemoradiotherapy-induced OM and was associated with the reduction of inflammation and repair.

Analysis of cell proliferation and pattern of invasion in oral squamous cell carcinoma.

Cell proliferation markers play an important role in the biological behavior of neoplasms. This study investigated the immunohistochemical expression of PCNA, Ki-67 and Cyclin B1 proteins based on the pattern of cell invasion in oral squamous cell carcinoma (OSCC). A total of 39 OSCC specimens and 13 samples of normal oral mucosa (control) were immunohistochemically analyzed. Protein expression was evaluated according to World Health Organization - Histological Malignancy Grading (WHO-HMG) and a specific grading system for invasion, graded from 1 to 4, varying from a consistently well-defined "pushing" border to diffuse infiltration and cellular dissociation, and was then correlated with clinical features. We found higher expression of Ki-67 and Cyclin B1 in OSCC when compared with the control group. High Ki-67 expression levels were more commonly seen in the floor of the mouth than in the tongue (P = 0.009). Cyclin B1 showed a positive correlation with histological grade, according to WHO-HMG criteria (P = 0.01). Our results suggest that Cyclin B1 is a reliable proliferation marker for indicating degree of tumor proliferation. Correlations between PCNA, Ki-67, Cyclin B1 and invasive tumor front with overall survival were not observed. Further studies are needed in order to elucidate whether cell proliferation activity at the tumor invasion front is related to prognosis.

Long-term effects of nifedipine on human gingival epithelium: a histopathological and immunohistochemical study.

The chronic usage of nifedipine is associated with the appearance of gingival overgrowth (GO). The frequency of GO associated with chronic nifedipine therapy remains controversial and the possible subclinical effects of this drug on the gingival epithelium should be investigated. We investigated the epithelial proliferation index and apoptosis rate, and their association with epithelial enlargement. Proliferation (Ki67 and Cyclin B1) and apoptosis (BCL2, Bax and p53) markers were identified by immunohistochemistry in twenty-one samples of gingival tissue from patients undergoing chronic treatment with nifedipine and in eleven samples of gingival tissue from healthy patients who did not use drugs associated with GO (control). Our results show that the epithelial tissue of nifedipine users has considerably longer rete pegs compared to control (P = 0.01). However, the density of Ki67(+) and Cyclin B1(+) cells was similar in both groups. Regarding apoptosis, we found more BCL2(+) cells in the nifedipine group when compared to controls (P = 0.12). An increase in Bax(+) cells in the nifedipine group compared to control (P = 0.003) was also seen, and slightly lower levels of p53(+) expression were observed (P = 0.51). Our results suggest that the chronic use of nifedipine is not associated with subclinical changes in gingival tissue.