Impact of photobiomodulation in a patient-derived xenograft model of oral squamous cell carcinoma.

BACKGROUND: Photobiomodulation therapy (PBMT) is an effective method for the prevention of oral mucositis. However, the effects of PBMT on oral squamous cell carcinoma (OSCC) have not yet been fully elucidated. This study aimed to evaluate the impact of PBMT in an OSCC-patient-derived xenograft (OSCC-PDX) model. METHODS: BALB/c nude mice with OSCC-PDX models were divided into Control, without PBMT (n = 8); Immediate irradiation, PBMT since one week after tumor implantation (n = 6); and Late irradiation, PBMT after tumors reached 200 mm3 (n = 6). OSCC-PDX were daily irradiated (660 nm; 100 mW; 6 J/cm2 ; 0,2 J/point) for 12 weeks. The tumors were collected and submitted to volumetric, histological, immunohistochemistry, and cell cycle analysis. RESULTS: No significant differences in the volumetric measurements (p = 0.89) and in the histopathological grade (p > 0.05) were detected between the groups. The immunohistochemical analysis of Ki-67 (p = 0.9661); H3K9ac (p = 0.3794); and BMI1 (p = 0.5182), and the evaluation of the cell cycle phases (p > 0.05) by flow cytometry also did not demonstrate significant differences between the irradiated and non-irradiated groups. CONCLUSION: In this study, PBMT did not impact the behavior of OSCC-PDX models. This is an important preclinical outcome regarding safety concerns of the use of PBMT in cancer patients.

Effect of low-level light therapy before radiotherapy in oral squamous cell carcinoma: An in vitro study.

Radiation therapy for head and neck squamous cell carcinoma (HNSCC) is associated with several complications. Although photobiomodulation (PBM) has radioprotective effects in normal tissue, it could also enhance the growth of neoplastic cells. Thus, the present study aimed to investigate the cellular response of oral squamous cell carcinoma with pre-exposure to low-level phototherapy before radiotherapy. SCC9, Cal-27, A431, and HaCaT cell lines were subjected to low-level light therapy and radiotherapy. The cells were treated with a single energy density (300 J/cm2) of a light-emitting diode (660 nm) prior to ionizing radiation at different doses (0, 2, 4, and 6 Gy). After 24 h, wound scratch, proliferation, clonogenic cell survival, cell death, and reactive oxygen species (ROS) analyses were performed to evaluate cell response. The cell lines pre-exposed to PBM at the analyzed dosage were radiosensitive. The treatment significantly reduced cell proliferation and clonogenic cell survival. Migration and cell death assays also revealed positive results, with the treatment group showing lower rate of migration and higher cell death than did the control group. Moreover, PBM effectively increased the intracellular levels of ROS. PBM at 300 J/cm2 is a promising radiosensitizing modality to reduce the radiation dose and avoid the intolerable side effects of radiotherapy for HNSCC, thus increasing the probability of successful treatment. However, further studies are needed to support and confirm the results.

The Effect of Low-level Laser Therapy on VEGF, IL-6 Expression and Viability of Oral Squamous Cell Carcinoma Cells.

Low-level laser therapy has shown successful results in the prevention and treatment of oral mucositis. One of the concerns about low-level lasers is their effects on remaining malignant cells in the area. Interleukin-6 is a multifunctional cytokine that plays an important role in a wide range of biological activities in increasing tumor functions, decreasing survival and resistance to chemo-radiotherapy. Vascular-endothelial growth factor increases tumor vascularization. It has been shown in the previous studies that LLLT can cause an increase of IL-6 and VEGF in some cells. The present thesis aims to study the effects of LLLT on IL-6 and VEGF expression, as well as cell viability on OSCC cells. Tumorigenic cells of an oral squamous cell carcinoma cell line were irradiated with 3 different diode lasers, and were compared to the control group (660 nm-200 mW-4 J cm-2 , 810 nm-200 mW-4 J cm-2 , 940 nm-200 mW-4 J cm-2 ). MTT assay, ELISA and RT-PCR were used to measure cell viability, IL-6 and VEGF expression. Cell viability of all laser-irradiated groups was significantly lower than the control group. VEGF expression increased in laser-irradiated groups. This was only significant in the 810 nm group. IL-6 protein secretion was significantly higher in all laser-irradiated groups compared to the control group.

Patterns of oral mucositis in advanced oral squamous cell carcinoma patients managed with prophylactic photobiomodulation therapy-insights for future protocol development.

To characterize oral sites affected by radiation-induced oral mucositis (OM) and related clinical outcomes in oral cancer patients subjected to prophylactic photobiomodulation therapy (PBMT). This study included advanced oral squamous cell carcinoma (OSCC) patients treated with prophylactic PBMT for OM. The site distribution of OM, OM grading (CTCAE NCI, Version 4.0, 2010), OM-related pain (VAS), analgesic protocol (WHO Analgesic Ladder), and use of enteral nutrition were evaluated weekly during treatment. Data analysis was performed using descriptive statistics expressed as median values and percentages. A total of 145 OSCC patients were included. OM most frequently affected the lateral border of the tongue (44.1%), buccal mucosa (37.2%), and labial mucosa (33.8%). Keratinized oral mucosa sites, including the tongue dorsum (6.21%), retromolar trigone (8.3%), and hard palate (2.76%), were less frequently affected. Peak OM scores were observed at weeks 5, 6, and 7, with severe OM (NCI grades 3 and 4) rates of 11%, 20%, and 25%, respectively. The cumulative occurrence of severe OM was 23%, which developed as early as week 3 and as late as week 7. The highest mean value of OM-related pain (2.7) was observed at the sixth week, and 13.8% of the patients required feeding support. This study showed, compared with studies that did not provide PBMT, reduced severity of mucositis, reduced pain and analgesic use, and reduced tube feeding in patients treated with PBMT. OM involving keratinized and non-keratinized surfaces should be included in the prophylactic PBMT to reduce severe OM in future studies.

Effects of photobiomodulation on cellular viability and cancer stem cell phenotype in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy; it has been shown that cancer stem cells (CSC) are present in OSCC and associated with tumor growth, invasion, metastasis, and therapeutic resistance. Photobiomodulation (PBM) is an alternative tool for oncologic treatment adverse effects such as oral mucositis (OM); however, controversy exists regarding the undesirable effects of PBM on tumor or CSC. This study aimed to evaluate in vitro, the effects of PBM, with the same dosimetric parameters as those used in the clinic for OM prevention and treatment, on OSCC cellular viability, as well as PBM's effect on CSC properties and its phenotype. OSCC cell lines were submitted to single or daily PBM with 3 J/cm2 and 6 J/cm2 and then the cellular viability was evaluated by MTT, NRU (neutral red uptake), and CVS (crystal violet staining). The CSC populations were evaluated by clonogenic formation assay, flow cytometry, and RT-qPCR. The single PBM with the 3 J/cm2 group was associated with increased cellular viability. Daily PBM with 3 J/cm2 and 6 J/cm2 was associated with a significant decrease in cellular viability. Additionally, daily PBM was not able to promote CSC self-renewal or the CD44high/ESAlow and CD44high/ESAhigh cellular phenotypes. Moreover, a decrease in the number of spheres and in the expression of the CSC related gene BMI1 was observed after daily PBM with 6 J/cm2. Daily PBM with 3 J/cm2 and 6 J/cm2 showed an inhibitory effect on cellular viability and was not able to promote the CSC self-renewal or phenotype.

Atención odontológica de pacientes oncológicos desde la perspectiva de actores institucionales en Cali, Colombia, 2019 / Dental care in cancer patients from the perspective of institutional actors in Cali, Colombia 2019

Objetivo: caracterizar la atención odontológica de los pacientes oncológicos desde la perspectiva de diferentes actores institucionales en Cali, durante el año 2019. Méto-dos: estudio de tipo cualitativo, descriptivo que empleó la entrevista semiestructurada como herramienta de recolección de datos. Las preguntas de la entrevista incluyeron las siguientes categorías: atención, acceso, integralidad, limitaciones, fortalezas y reco-mendaciones. Participaron quince actores institucionales relacionados con la atención del paciente con cáncer. Además, se realizó una revisión documental en las Institucio-nes Prestadoras de Servicios de Salud. Las preguntas. Resultados: los hallazgos signifi-cativos con los que se cuentan son: la identificación de la ausencia de guías de atención odontológica para los pacientes con cáncer, la presencia de barreras personales, eco-nómicas, organizacionales, sociales y culturales en el acceso al servicio y la no inclusión del profesional de odontología en las rutas de atención de cáncer en el Ministerio de Salud y Protección Social. Como limitaciones se identificaron el fraccionamiento del servicio y la priorización de la patología de base; mientras que como fortaleza principal se reconoce la capacidad instalada. Así, las recomendaciones, dirigidas a los diferentes sectores, procuran por el establecimiento de guías de atención, una mayor articulación entre entidades y la visibilización de la problemática. Conclusión: aunque la ciudad tie-ne suficiente capacidad instalada, los entrevistados manifestaron que no cuentan con una directriz desde el ente rector, por lo tanto, se evidencian barreras en la atención odontológica. Asimismo, se determina la falta de articulación entre las diferentes insti-tuciones que impide el cumplimiento de la atención integral y equitativa.

Objective: To characterize dental care in cancer patients from the perspective of different health institutional actors in Santiago de Cali, Colombia, 2019. Methods: This is a qualitative, descriptive study. Semi structured interviews were used as a research technique, oriented to fifteen institutional health actors who play a role in cancer care in Cali, Colombia. The questions included the following six axial categories: oral care in cancer patients, access, comprehensive care, restrictions, strengths, and suggestions for improvement from the institutional actors. A textual transcription was done after the interviews. Results: There are no Guides of oral care in cancer patients from the Ministry of health and social protection. Access to oral care service has personal, economical, organizational, social, and cultural barriers. Cancer care routes from de Ministry of Health do not include dentists as part of the multidisciplinary teams. Restrictions such as fragmentation of the service and prioritization of the primary pathology were described. Installed capacity for oral health services was mentioned as a strength; and the main recommendations were to establish Guides for oral care, better coordination between health entities and highlighting the lack of oral care in cancer patients. Conclusions: Even though Cali has a sufficient installed capacity, the interviewees stated that they don ́t have a guideline from the Ministry of Health and therefore evident barriers in oral care in cancer patients are found. Lack of articulation between Health entities prevents compliance of a comprehensive and equitable care. Recommendations to different sectors were made by respondents in order to improve dental care in cancer patients.

Effects of continuity of care on the postradiotherapy survival of working-age patients with oral cavity cancer: A nationwide population-based cohort study in Taiwan.

OBJECTIVES: Cancer of the oral cavity, a well-known global health concern, remains one of most common causes of cancer mortality. Continuity of care (COC), a measurement of the extent to which an individual patient receives care from a given provider over a specified period of time, can help cancer survivors process their experiences of dealing with the illness and recuperation; however, limited research has focused on the survival rate of working-age patients with oral cancer. METHODS: A total of 14,240 working-age patients (20 0.38) and non-high COC (COCI ≤ 0.38) groups. After propensity-score matching, the mortality risk in the low and intermediate COC groups was also found to be significantly higher than that in the high COC group (aHR = 1.178, 95% CI = 1.074-1.292, p < 0.001 and aHR = 1.189, 95% CI = 1.107-1.277, p = 0.001, respectively). CONCLUSIONS: In Taiwan, COC and prior dental treatment before RT significantly affected the survival rate of working-age patients with oral cancer. This result merits policymakers' attention.

High energy density LED-based photobiomodulation inhibits squamous cell carcinoma progression in co-cultures in vitro.

Current management of oral potentially malignant disorders is careful monitoring. Unfortunately, the 'watch and wait' approach only generates anxiety and a feeling of powerlessness, especially to those caring for patients. Photobiomodulation (PBM) has emerged as a potential strategy to inhibit possible transforming cells. The aim of this study was to investigate the effect of LED-based PBM on the progression of malignant invasion into a fibroblast-based stroma. An in vitro model of carcinoma in situ (CIS) containing stromal fibroblasts and carcinoma cells in co-culture was used to study the effect of PBM on the expansion of CIS colonies. A second model of co-culture (cells separated by membrane), was used to study cell counts, viability and apoptosis following PBM at high doses (36 J/cm2). The data was analyzed using Kruskal-Wallis, Dunn's test and non-linear regression, wherever appropriate. PBM was able to inhibit the expansion of CIS colonies as well as the total number of colonies after 72 h of treatment (p < 0.05). Cell viability, apoptosis and death assays revealed an overall advantage of stromal fibroblasts over carcinoma cells after high-dose PBM. In conclusion, LED-based PBM at high doses inhibited the progression and number of oral squamous cell carcinoma colonies without affecting the surrounding stromal fibroblasts in vitro.

Efficacy of low-level laser for treatment of cancer oral mucositis: a systematic review and meta-analysis.

Review effectiveness of low-level laser therapy (LLLT) in the curative treatment of oral mucositis (OM) in patients receiving cancer therapy. A systematic review with meta-analysis was performed using Medline, Embase, and Cochrane Library databases according to PRISMA guidelines, to identify randomized controlled trials (RCT) on OM in patients during and/or after cancer therapy and in which the therapeutic approach was LLLT, with wavelengths between 632 and 970 nm. We considered grade of OM as a dichotomous variable (such as an improvement or not in severe OM on the seventh day of therapy), with the analysis of subgroups of adult patients or children and adolescents and as a continuous variable with determination of the time for the complete resolution and the subgroup analysis occurred with the strata of the samples by treatment only with chemotherapy or chemotherapy and radiotherapy. This paper's protocol was registered a priori at https://www.crd.york.ac.uk/PROSPERO . We found five RCT (total of 315 patients) with adequate methodology. LLLT was effective, presenting a 62% risk reduction of severe mucositis on the seventh day of evaluation (RR = 0.38 [95% CI, 0.19-0.75]). When we analyzed subgroups, RR was 0.28 (95% CI 0.17-0.46) in the adult studies and 0.90 (95% CI, 0.46-1.78) in the studies with children and adolescents. We demonstrated a mean reduction of 4.21 days in the time of complete resolution of OM (CI - 5.65 to - 2.76) in favor of LLLT. There is moderate evidence that LLLT is effective in resolving OM lesions in adult patients undergoing cancer therapy. LLLT demonstrates potential for decreasing the resolution time of OM lesions by approximately 4.21 days.

Photobiomodulation is associated with a decrease in cell viability and migration in oral squamous cell carcinoma.

The treatment of squamous cell carcinoma (SCC) involves surgery, chemotherapy, and/or radiotherapy, which can cause mucositis (inflammation of the oral mucosa that causes considerable pain and can compromise the continuity of oncological treatment). Photobiomodulation (PBM) has been successfully used in the treatment of mucositis, but doubts arise regarding the use of laser for areas in which tumor cells may remain. In this study, the effect of PBM on the viability, mitochondrial activity, proliferation, apoptosis, and migration of cells derived from oral SCC was evaluated. SCC9 cells were irradiated with laser (660 and 780 nm, using 11 dosimetric parameters) and submitted to mitochondrial and caspase 3 activity tests after 1 and 3 days. Based on the results, cell viability (neutral red assay), proliferation (BrdU assay), and migration (scratch-wound assay) were evaluated using only the dosimetric parameters recommended for mucositis. Non-irradiated cells served as the control. The experiments were performed in triplicate. The 11 parameters diminished mitochondrial activity and induced tumor cell apoptosis. Using the parameters recommended for mucositis, irradiation with 780 nm (70 mW, 4 J/cm2) proved to be the safest and led to a reduction in cell viability, the induction of apoptosis, and a reduction in the migration capacity of the tumor cells.

Clinicopathologic Analysis of Oral Squamous Cell Carcinoma After 125I Interstitial Brachytherapy.

Oral squamous cell carcinoma is a common malignancy in the head and neck region. Brachytherapy after radical surgery has achieved much progress as a cancer adjuvant treatment. This study focused on the pathologic characteristics of the patients with oral squamous cell carcinoma who underwent seed implantation after radical surgery, and the relationship of these characteristics with prognosis. Thus, 76 patients with oral squamous cell carcinoma, who were treated with surgery and subsequently with iodine 125 (125I) radioactive seed implantation, were recruited in this study. We summarized the demographic information, tumor size, location, clinical stage, prognosis, and pathologic characteristics, and discussed the correlations between prognosis and histologic features of oral squamous cell carcinoma after seed implantation. The data showed that the median age was 64 years old, the male/female ratio was 47/29, and the frequent location of the carcinoma was the tongue (35.5%). The median follow-up time was 126 months, and of the patients, 52 (68.4%) exhibited recurrent tumors. The 5-year survival rate was 81.5%, and the local control rate in 6 months was 95.3%. Microscopically, 25 cases demonstrated lymph node metastasis, there was obvious necrosis in 13 cases, and 55 cases exhibited confirmed adjacent tissue invasion including muscle, gland, vessel, nerve, and bone infiltration. Among those, vascular infiltration (13 cases) was significantly correlated with tumor recurrence ( P < .05). This study suggests that detailed pathologic diagnosis and microscopic description, especially of vascular infiltration, was valuable in the prognosis prediction of brachytherapy.

Selenium Influences Trace Elements Homeostasis, Cancer Biomarkers in Squamous Cell Carcinoma Patients Administered with Cancerocidal Radiotherapy

In the perspective of selenium as an antioxidant and anti-carcinogen, so far no strong intervention trials with selenium over radiation-treated oral squamous cell carcinoma cases have been conducted, to examine the response of the disease and the subsequent biochemical alterations. In the present study, untreated oral cancer cases (Gp II) were compared with radiation-treated groups with and without selenium (Gp IIa, IIb), forward to find the trace elements and cancer biomarkers status, at a follow-up of 6 months. Severe alteration in the trace elements levels of Se, Cu, Fe, Zn, Na, K, Ca, Cl, were noticed in Gp II. Though Gp IIa showed slight improvement, administration of selenium (Gp IIb) improved the level of all these elements to a greater extent (p<0.001). GpII and IIa showed increased level of bio markers 5'-nucleotidase, PschE, LAP, γ-GTP, LDH, SGOT, SGPT, ACP, ALP, CPK, TNF, CEA, AFP, Scc-Ag. The greater extent of restitution to near normalcy was observed in patients given selenium (Gp IIb) (p<0.001). Owing to the fact that selenium scavengers oxidants and hence decelerate carcinogenesis by eliminating tumors, so the tumor released constituents into the systemic circulation declined significantly. Therefore, the outcome of the study suggests selenium as a valuable therapeutic measure as adjuvant for oral cancer patients undergoing cancerocidal radiotherapy.

Dosimetry study on radioactive particle brachytherapy in oral carcinoma.

PURPOSE: To investigate the therapeutic effects of different doses of 125I radioactive particle brachytherapy on oral cancer. METHODS: Between September 2012 and September 2015, 78 patients with oral cancer who received 125I radioactive particle brachytherapy for the first time in our hospital were enrolled in this study. Patients were divided into high dose (≥3) and low dose (<3) groups. The treatment outcome, serum tumor marker levels and the expression levels of autophagy and apoptotic genes in tumor cells were compared between groups. RESULTS: Complete remission (CR)+partial remission (PR) ratio in the high dose group was significantly higher than that of the low dose group. Stable disease (SD)+ progressive disease (PD) ratio was significantly lower in the high dose group. The serum levels of TSGF, SCCA, CEA, CA125, CA15.3, CA19.9 and PSA oral cancer markers were significantly lower than those of the low dose group. In the high dose group, the expression levels of Beclin-1 and MAP1LC3 (autophagic genes) mRNAs were significantly higher than those of the low dose group, while the expression levels of EMMPRIN and MMP-14 (invasive genes) mRNAs were significantly lower in the high dose group. Also survival rates in the responsive patients were significantly better in comparison to non-responsive patients. CONCLUSION: High dose particle brachytherapy with radioactive 125I is a safe and effective treatment and its clinical results were more beneficial than the low dose therapy.

Postoperative iodine-125 interstitial brachytherapy for the early stages of minor salivary gland carcinomas of the lip and buccal mucosa with positive or close margins.

BACKGROUND: The purpose of this study was to present our preliminary exploration of safety and efficacy of postoperative low-dose-rate brachytherapy for the early clinical stages of minor salivary gland carcinomas of the lip and buccal mucosa. METHODS: Twenty-seven patients with the early stages of minor salivary gland carcinomas of the lip and buccal mucosa received postoperative 125 I seed interstitial brachytherapy from March 2005 to May 2015. Actuarial likelihood estimates for local control, overall survival, and disease-free survival were calculated by Kaplan-Meier method. RESULTS: The actuarial 3-year, 5-year, and 10-year local control rates were 94.7%, 82.9%, and 82.9%, respectively. The actuarial 3-year, 5-year, and 10-year overall survival rates were 93.3%, 93.3%, and 77.8%, respectively. No patient experienced toxicity above grade 2. CONCLUSION: Postoperative 125 I seed interstitial brachytherapy is an alternative to radical surgery for early stages of minor salivary gland carcinomas of the lip and buccal mucosa, which offers satisfactory cosmetic and functional outcomes. © 2017 Wiley Periodicals, Inc. Head Neck 39: 572-577, 2017.

Radiotherapy for oral cancer decreases the cutaneous expression of host defence peptides.

INTRODUCTION: Bacterial resistance against antibiotics has become an increasing challenge in the treatment of cutaneous infections. Consequences can be severe, especially in infected wounds following previous local radiotherapy. Certain endogenous peptide antibiotics, the host defence peptides (HDPs), exhibit broad-spectrum antimicrobial activity and promote wound healing. Their use as supplements to conventional antibiotics is a current topic of discussion; however, knowledge of their quantities in healthy and compromised tissue is a prerequisite for such discussion. To date, no data concerning HDP quantities in irradiated skin are available. METHODS: Expression profiles of the genes encoding HDPs, namely human beta-defensin-1 (DEFB1, hBD-1), beta-defensin-2 (DEFB4A, hBD-2), beta-defensin-3 (DEFB103, hBD-3) and S100A7, were assessed in samples of non-irradiated and irradiated neck. RESULTS: A reduction in the expression of all of the examined genes was observed in irradiated skin when compared with non-irradiated skin (statistically significant in the case of S100A7, P = 0.013). Immunohistochemistry revealed differences in HDP distribution with respect to the epithelial layers. CONCLUSION: The study demonstrates a significant reduction in HDP gene expression in neck skin as a result of radiotherapy. These findings might represent a starting point for novel treatments of cutaneous infections in irradiated patients, such as topical supplementation of synthetic HDP.

Photomodulation of the osteoclastogenic potential of oral squamous carcinoma cells.

The treatment for oral cancer usually involves surgical excision followed by chemotherapy and/or radiotherapy. The combination of these therapies generally promotes a serious inflammation of the mucosa of the digestive tract, denominated mucositis, which compromises continuity of treatment. Photobiomodulation (PBM) therapy has been used successfully to reduce the oral mucositis, however there is still some controversy regarding the effects of this therapy on unintentionally irradiated tumor cells that may remain after cancer treatment. The aim of this study was to analyze the effect of PBM therapy (using parameters for mucositis) on the modulation of osteoclastogenic potential of a cell line derived from human lingual squamous cell carcinoma (SCC9). Previously irradiated SCC9 cells were co-cultured with human osteoclast precursors. Co-cultures performed with non-irradiated SCC9 cells served as control. After 7, 14 and 21 days the co-cultures were evaluated for the tartrate-resistant acid phosphatase (TRAP) activity, an osteoclastogenic marker. Additionally, the monocultures of SCC9 cells (non-irradiated and irradiated) were analyzed for cell viability/proliferation and for the expression of IL-11 and PTHrP. The irradiation of SCC9 cells with PBM with an energy density of 4 J/cm2 decreased the pro-osteoclastogenic potential of those cells. This may represent a potential useful side effect of PBM therapy. PBM (using recommended parameters for mucositis treatment) decreases the osteoclastogenic potential of oral squamous carcinoma cells.

High-dose-rate interstitial brachytherapy in oral cancer-Its impact on quality of life.

PURPOSE: The aim of the study was to assess the impact of high-dose-rate (HDR) interstitial brachytherapy on quality of life (QOL) in oral cancer. METHODS AND MATERIALS: Thirty-two patients of oral cancer treated at our institute from January 2010 to December 2014 with radical radiotherapy (external beam radiotherapy + brachytherapy) were included for analysis; 30 patients received external beam radiotherapy (50-54 Gy) and HDR brachytherapy boost (18-24.5 Gy); 2 patients received radical HDR brachytherapy (31.5 Gy). Quality of life (QOL) was assessed by Telugu, Hindi, and English versions of EORTC Quality of Life Core-30 and EORTC Quality of Life Head and Neck Module (QLQ H&N35) before treatment, at 3 months, 6 months, 1 year, and 2 years after treatment. RESULTS: Of the 32 patients, 2 patients died and 1 patient progressed on followup; 2 patients were re-irradiation cases. On excluding these cases, 27 patients were available for analysis. The followup duration was 6-55 months. At the time of analysis, 91% (29) patients were disease free, 3% (1) progressed, and 6% (2) died. At the end of 2 years, none of the QLQ-C30 functional scores fell below the baseline. Pain, swallowing, sensory, speech, social contact, and social eating worsened at 3 months but improved over 2 years (p < 0.001). Sexuality and financial status showed delayed improvement (p < 0.001). Among the head and neck parameters, dry mouth and sticky saliva were significant determinants of QOL with delayed improvement (p < 0.001). The impact of age, sex, and tumor stage and on QOL was analyzed. Women reported a poorer QOL for physical and emotional parameters, social eating, weight loss, and fatigue. Tumor stage significantly affected QOL, with early stages showing a better QOL. CONCLUSIONS: Almost all patients regained normal function after treatment and reported an excellent QOL at 2 years. However, tumor stage significantly affected the QOL.

(125)I interstitial brachytherapy for the treatment of myoepithelial carcinoma of the oral and maxillofacial region.

PURPOSE: This study evaluated the treatment of myoepithelial carcinoma (MC) of the oral and maxillofacial region with radioactive iodine ((125)I) seed implantation. METHODS AND MATERIALS: Twenty-seven patients with MC in the oral and maxillofacial region were treated with (125)I seed implantation between March 2006 and October 2012. Thirteen of the 27 patients (8/8 patients with primary disease and 5/19 patients with recurrent disease) were treated on an adjuvant setting after resections, and the other 14 patients were treated by brachytherapy after a recurrence precluding a surgical resection for salvage. The sites of the MC were the parotid for 18 patients, oral cavity for 2 patients, and base of skull for 7 patients. Recurrence-free survival (RFS), overall survival (OS) rates, and side effects were retrospectively reviewed. RESULTS: Patients were followed for 6-105 months (median 37 months). The 3- and 5-year RFS rates were 51.9% and 46.1%, respectively. The 3- and 5-year OS rates were 68.6% and 51.5%, respectively. The OS and RFS were significantly better among the 8 patients treated upfront in comparison with the 19 patients treated for salvage at relapse. The OS was worst for the 7 patients with base of skull region disease. No severe complications were observed during followup. CONCLUSIONS: This study showed (125)I brachytherapy is a feasible and effective modality for the treatment of MC. These findings should be interpreted cautiously due to the small number of patients and the relatively short followup.

Selective cytotoxic effects of low-power laser irradiation on human oral cancer cells.

BACKGROUND AND OBJECTIVES: Low-power laser irradiation (LPLI) is known to regulate cell proliferation and migration in clinical use. Recent studies have shown that LPLI induces cell death in some certain types of cancer cell lines. However, the cytotoxic selectivity of LPLI for cancer cells is not fully understood. The aim of this study was to compare the cytotoxic effects of LPLI in both human oral cancer OC2 cells and normal human gingival fibroblast (HGF) cells. MATERIALS AND METHODS: LPLI at 810 nm with an energy density from 10 to 60 J/cm(2) was used to irradiate human oral cancer OC2 cells and normal HGF cells. RESULTS: We found that LPLI significantly diminished cell viability of human oral cancer OC2 cells due to cell cycle arrest at the G1 phase and the induction of cell death but that it had no or little effects on cell cycle progression and death in normal HGF cells. Moreover, the production of reactive oxygen species (ROS) and the loss of mitochondrial membrane potential (MMP) were elevated in human oral cancer OC2 cells compared with the un-irradiated cells. In contrast, these effects remained unchanged in normal HGF cells after exposure to LPLI. LPLI also induced apoptosis in caspase-3 dependent manner in human oral cancer OC2 cells, a mode of action that could be mediated by ROS and mitochondrial damage. CONCLUSION: Our findings imply LPLI might be a potential therapy for oral cancers.

O2 and Ca(2+) fluxes as indicators of apoptosis induced by rose bengal-mediated photodynamic therapy in human oral squamous carcinoma cells.

OBJECTIVE: Photodynamic therapy (PDT) triggers various cellular responses and induces cell death via necrosis and/or apoptosis. This study evaluated the feasibility of using O2 and Ca(2+) fluxes as indicators of apoptosis induced by rose bengal (RB)-mediated PDT in human oral squamous carcinoma cells (Cal27 cells). METHODS: Intracellular reactive oxygen species (ROS) generation was assessed by the dichloro-dihydro-fluorescein diacetate (DCFH-DA) method. Real-time O2 and Ca(2+) flux measurements were performed using the noninvasive micro-test technique (NMT). Apoptosis of the PDT-treated cells was confirmed by 4'6-diamidino-2-phenylindole-dilactate staining. The activation of apoptosis-related molecules was examined using Western blot. We assayed the effects of the fluctuation of O2 and Ca(2+) flux in response to PDT and the apoptotic mechanism, by which ROS, O2, and Ca(2+) synergistically may trigger apoptosis in PDT-treated cells. RESULTS: Real-time O2 and Ca(2+) flux measurements revealed that these indicators were involved in the timely regulation of apoptosis in the PDT-treated cells and were activated 2 h after PDT treatment. RB-mediated PDT significantly elicited the generation of ROS by approximately threefold, which was critical for PDT-induced apoptosis. Cytochrome c and cleaved caspase-3, caspase-9 and poly ADP ribose polymerase (PARP) were overexpressed, and the data provided evidence that 2 h was considered to be the key observation time in RB-mediated PDT-induced apoptosis in Cal27 cells. CONCLUSIONS: Our collective results indicated that the effects of O2 and Ca(2+) fluxes may act as a real-time biomonitoring system of apoptosis in the RB-PDT-treated cells. Also, RB-mediated PDT can be a potential and effective therapeutic modality in oral squamous cell carcinoma.