Overexpression of ALDH1 and EMT marker profile are linked with unfavorable outcome in head and neck cancer

BACKGROUND: The aim of this research was to assess the expression of aldehyde dehydrogenase 1 (ALDH1) and epithelial-mesenchymal transition (EMT) markers in head and neck squamous cell carcinoma (HNSCC), and to correlate them with the clinical and histopathological parameters of a patient cohort with follow-up over an 8-year period. MATERIAL AND METHODS: For this, seventeen HNSCC and non-neoplastic adjacent epithelium (AE) samples were subjected to laser microdissection and real-time PCR to evaluate the mRNA expression of ALDH1, E-cadherin (E-CAD), N-cadherin (N-CAD), and vimentin (VIM). Also, immunohistochemistry was performed for ALDH1, E-CAD, N-CAD, and VIM in the tumor center (TC), invasion front (IF), and AE of the seventeen samples. Mann-Whitney, Kruskal-Wallis and Chi-square tests were used to correlate the mRNA and immunohistochemical ex-pression with different variables, considering p < 0.05. Kaplan-Meier curves were produced for local recurrence, regional metastasis and treatment. RESULTS: A mRNA overexpression of ALDH1 in primary tumors was associated with regional metastasis and a high ALDH1 immunostaining was related to metastasis and a worse patient outcome. Additionally, a favorable outcome was associated with the transition phase and an unfavorable outcome was associated with EMT event. An overall 26.9 months was observed with longer survival associated with surgery and radiotherapy. CONCLUSIONS: However, due to the intense variability inherent to the indicator proteins in the EMT process, the complete profile markers related to this biological process should be continuous investigated

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Treatment of actinic cheilitis: a systematic review.

OBJECTIVES: Actinic cheilitis is a potentially malignant disorder caused by excessive sun exposure. It affects the lower lip of individuals, mostly those with light skin color. Different treatments have been proposed for AC; however, no consensus has been reached on the best option available. MATERIALS AND METHODS: The present study describes the results of a computer-based systematic search conducted on electronic databases to identify the best therapies. RESULTS: A total of 29 journal articles were selected, and the results were divided according to the type of treatment employed: laser therapy, chemotherapy agents, surgical treatment, and application of anti-inflammatory agents. Clinically, photodynamic therapy showed positive results, with improvement in up to 100% of the patients; however, histopathological improvement varied greatly, from 16 to 100%. Among the chemotherapeutic agents assessed, imiquimod showed the best results: clinical improvement in 80 to 100% of the patients, and histopathological improvement in 73 to 100%. Regarding studies describing surgical approaches, the main focus was the search for the best technique, rather than the cure of AC. Finally, studies employing anti-inflammatory agents are sparse and have small samples, thus providing limited results. CONCLUSION: The scientific evidence available on the treatment of AC is scarce and heterogeneous, photodynamic therapy, and imiquimod application are promising. CLINICAL RELEVANCE: The study of the treatments for AC in the form of a systematic review allows us to evaluate the results against the different treatments. Being a potentially malignant lesion, it is important to seek evidence about the best results found.

Non-invasive therapies for management of temporomandibular disorders: a systematic review

Introduction: As a multifactorial disease, temporomandibular disorders (TMD) require a complex therapeutic approach, being noninvasive therapies the first option for most patients. The aim of this study was to perform a systematic review to analyze the most common non-invasive therapies used for TMD management. Methods: The review was done by searching electronic databases to identify controlled clinical trials related to pharmacologic and non-invasive treatments. Of all potential articles found, 35 were included in this review. Results: Low-level laser therapy (LLLT), occlusal splints (OS) and oral exercises/ behavior education (OE/BE) were the most common therapies used. LLLT showed significant results in pain and movement improvement in most studies. OS was usually combined to other therapies and resulted in improvement of pain. OE/BE showed significant results when combined with ultrasound, LLLT, and manual therapy. Conclusions: Non-invasive treatments can provide pain relief and should be prescribed before surgical procedures. LLLT was the therapy with the higher number of studies showing positive results. Based in heterogeneity of treatment protocols, diagnostic and outcomes criteria used, new well-designed randomized controlled trials (RCT) are necessary. (AU)

Comparative effectiveness of photobiomodulation and manual therapy alone or combined in TMD patients: a randomized clinical trial.

The effectiveness of photobiomodulation (PBM) and manual therapy (MT), alone or combined (CT), were evaluated in pain intensity, mandibular movements, psychosocial aspects, and anxiety symptoms of temporomandibular disorder (TMD) patients. Fifty-one TMD patients were randomly assigned to three groups: the PBM group (n = 18), which received PBM with 808 nm, 100 mW, 13.3 J/cm2, and 4 J per point; the MT group (n=16) for 21 minutes each session on masticatory muscles and temporomandibular joint TMJ; and the CT group (n = 17), applied during twelve sessions. Seven evaluations were performed in different moments using visual analogue scale (VAS), Research Diagnosis Criteria for Temporomandibular Disorders (RDC/TMD) Axis I and II, and Beck anxiety inventory (BAI). All groups demonstrated reductions in pain and improvement in jaw movements during treatment and at follow-up (< 0.001). The assessment of psychosocial aspects of TMD, comparing baseline and follow-up in all treatment groups, revealed that treatment did not promote modification in the intensity of chronic pain (p > 0.05). However, depression symptoms showed a reduction in PBM and CT groups (p≤0.05). All treatments promoted reduction in physical symptoms with and without pain and enhancement of jaw disabilities (p ≤ 0.05). MT promotes improvement in 5 functions, PBM in 2, and CT in 1 (p < 0.001). BAI analysis revealed that all treatments lead to a reduction in anxiety symptoms (p≤0.05). All protocols tested were able to promote pain relief, improve mandibular function, and reduce the negative psychosocial aspects and levels of anxiety in TMD patients. However, the combination of PBM and MT did not promote an increase in the effectiveness of both therapies alone.

Comparative effectiveness of photobiomodulation and manual therapy alone or combined in TMD patients: a randomized clinical trial

Abstract The effectiveness of photobiomodulation (PBM) and manual therapy (MT), alone or combined (CT), were evaluated in pain intensity, mandibular movements, psychosocial aspects, and anxiety symptoms of temporomandibular disorder (TMD) patients. Fifty-one TMD patients were randomly assigned to three groups: the PBM group (n = 18), which received PBM with 808 nm, 100 mW, 13.3 J/cm2, and 4 J per point; the MT group (n=16) for 21 minutes each session on masticatory muscles and temporomandibular joint TMJ; and the CT group (n = 17), applied during twelve sessions. Seven evaluations were performed in different moments using visual analogue scale (VAS), Research Diagnosis Criteria for Temporomandibular Disorders (RDC/TMD) Axis I and II, and Beck anxiety inventory (BAI). All groups demonstrated reductions in pain and improvement in jaw movements during treatment and at follow-up (< 0.001). The assessment of psychosocial aspects of TMD, comparing baseline and follow-up in all treatment groups, revealed that treatment did not promote modification in the intensity of chronic pain (p > 0.05). However, depression symptoms showed a reduction in PBM and CT groups (p≤0.05). All treatments promoted reduction in physical symptoms with and without pain and enhancement of jaw disabilities (p ≤ 0.05). MT promotes improvement in 5 functions, PBM in 2, and CT in 1 (p < 0.001). BAI analysis revealed that all treatments lead to a reduction in anxiety symptoms (p≤0.05). All protocols tested were able to promote pain relief, improve mandibular function, and reduce the negative psychosocial aspects and levels of anxiety in TMD patients. However, the combination of PBM and MT did not promote an increase in the effectiveness of both therapies alone.

Low Doses of Curcuma longa Modulates Cell Migration and Cell-Cell Adhesion.

Cell invasion and metastasis are involved in clinical failures in cancer treatment, and both events require the acquisition of a migratory behavior by tumor cells. Curcumin is a promising natural product with anti-proliferative activity, but its effects on cell migration are still unclear. We evaluated the effects of curcumin on the proliferation, apoptosis, migration, and cell-cell adhesion of keratinocyte, oral squamous cell carcinoma (OSCC), and fibroblast cell lines, as well as in a xenograft model of OSCC. Curcumin (2 µM) decreased cell proliferation in cell lines with mesenchymal characteristics, while cell death was detected only at 50 µM. We observed that highly migratory cells showed a decrease on migration speed and directionality when treated with 2 or 5 µM of curcumin (50% and 40%, respectively, p < 0.05). Using spheroids, we observed that curcumin dose dependently decreased cell-cell adhesion, especially on tumor-derived spheroids. Also, in a xenograft model with patient-derived OSCC cells, the administration of curcumin decreased tumor growth and aggressiveness when compared with untreated tumors, indicating the potential antitumor effect in oral cancer. These results suggest that lower doses of curcumin can influence several steps involved in tumorigenesis, including migration properties, suggesting a possible use in cancer therapy. Copyright © 2017 John Wiley & Sons, Ltd.

Effect of different presentations of resveratrol on cell proliferation and epitelial thickness of the oral mucosa of wistar rats

Introduction: Grape is one of the most important fruit crops across the world and can be consumed in different ways. There has been a growing interest in the role of antioxidants such as resveratrol, which can be found in grape skin, in oral and dental tissues. Thus, the objective of this study was to analyze the effect of different presentations of resveratrol on cell proliferation and epithelial thickness of the oral mucosa of Wistar rats. Methods: Fifty male Wistar rats were randomly divided into five groups: water/control, red wine, grape juice, 12% alcoholic solution/ethanol and aqueous solution of resveratrol. Samples of palatal and tongue mucosa were collected for a histomorphometric analysis using hematoxylin-eosin staining and the argyrophilic nucleolar organizer region (AgNOR) technique for quantification of cell proliferation. Results: As to epithelial thickness, both the tongue and the palate showed a statistically significant difference between the control group and the other groups, with greater decrease in the resveratrol and the wine groups. In the suprabasal layer of both the tongue and the palate epithelium, red wine reduced the rate of cell proliferation, while ethanol increased it. In the basal layer of the tongue epithelium, there was a statistically significant difference between the control, the grape juice and the resveratrol groups and the ethanol group, with increased cell proliferation in the ethanol group. Conclusions: Wine does not interfere in the physiological renewal of the basal layer of the buccal epithelium and exerts a protective action by reducing the cell proliferation rate of the suprabasal layer (AU)

Location of injected polymethylmethacrylate microspheres influences the onset of late adverse effects: an experimental and histopathologic study.

Polymethylmethacrylate (PMMA) has been widely used in the correction of wrinkles because of its long-lasting cosmetic improvements. However, side effects and complications may occur, and its clinical appearance on the oral mucosa can be similar to that of inflammatory or neoplastic disease. The aim of this research was to compare the clinical and histopathologic responses to PMMA injected by two different methods. Twenty-two rats received an injection of PMMA using the tunneling technique (gold standard), with subcutaneous deposition of the filler in the face, or a variation of the technique with transcutaneous submucosal deposition of the filler in the cheek. The tissue reaction was analyzed clinically every 24 hours during the first week, then once a week for the following 3 months. Histologic evaluation was based on the local inflammatory response to the filler. No clinical changes were observed during the initial evaluation period (0-14 days). After 14 days, only the submucosal group showed extra-oral enlargement (n=4, 18.2%). Histopathologic analysis revealed nodule formation in four animals (18.2%) in the submucosal group, with no nodules observed in the subcutaneous group. The data obtained in this study demonstrate that the technique used to deliver the filler may influence the risk of adverse reactions.