Methyltransferase-like 3-induced N6-methyladenosine upregulation promotes oral squamous cell carcinoma by through p38.

BACKGROUND: Oral squamous cell carcinoma (OSCC), a main type of squamous cell cancer, is associated with considerable morbidity and mortality. Recent reports suggested methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) modification to be an essential regulator in the fate determination of stem cells. However, the functional significance of METTL3 in OSCC remains largely unknown. METHODS: METTL3 expression was examined in OSCC patient samples, followed by correlation analysis against clinical tumor features. Functional assays, such as assessment of surface marker expression, colony forming, BrdU incorporation, tumor xenograft assay, and m6A dot blot, were conducted to study the impact of METTL3 knockdown (KD) in OSCC cells. RESULTS: High METTL3 expression was positively correlated with more severe clinical features of OSCC tumors. METTL3 KD caused impairment of stem-like capacities in OSCC cells, such as tumorigenicity in vivo and colony-forming ability in vitro. Furthermore, METTL3-KD and cycloleucine, a methylation inhibitor, decreased m6A levels and down-regulated p38 expression in OSCC cells. On the contrary, the impaired cell proliferation capacity of OSCC cells after METTL3-KD was restored by exogenous expression of p38. CONCLUSION: Our findings identified m6A methyltransferase METTL3 as a key element in the regulation of tumorigenesis in OSCC.

Single- and Cross-Modality Near Duplicate Image Pairs Detection via Spatial Transformer Comparing CNN.

Recently, both single modality and cross modality near-duplicate image detection tasks have received wide attention in the community of pattern recognition and computer vision. Existing deep neural networks-based methods have achieved remarkable performance in this task. However, most of the methods mainly focus on the learning of each image from the image pair, thus leading to less use of the information between the near duplicate image pairs to some extent. In this paper, to make more use of the correlations between image pairs, we propose a spatial transformer comparing convolutional neural network (CNN) model to compare near-duplicate image pairs. Specifically, we firstly propose a comparing CNN framework, which is equipped with a cross-stream to fully learn the correlation information between image pairs, while considering the features of each image. Furthermore, to deal with the local deformations led by cropping, translation, scaling, and non-rigid transformations, we additionally introduce a spatial transformer comparing CNN model by incorporating a spatial transformer module to the comparing CNN architecture. To demonstrate the effectiveness of the proposed method on both the single-modality and cross-modality (Optical-InfraRed) near-duplicate image pair detection tasks, we conduct extensive experiments on three popular benchmark datasets, namely CaliforniaND (ND means near duplicate), Mir-Flickr Near Duplicate, and TNO Multi-band Image Data Collection. The experimental results show that the proposed method can achieve superior performance compared with many state-of-the-art methods on both tasks.

Clinical Correction of Complete Median Cleft of the Mandible and Lower Lip: A 17-Year Follow-Up of a Case Report With Literature Review.

The median cleft of the mandible and lower lip is an extremely rare congenital maxillofacial deformity, and the therapeutic options are controversial. To evaluate the clinical characteristics and identify a better choice of treatment modes used among us and others, we reviewed 34 relevant literature and herein describe a 17-year follow-up of a case with a median cleft of the mandible and lower lip. Based on the literature and our case with good functional and aesthetical outcomes, we propose a prospective clinical treatment: Patients of Tessier 30 cleft associated with cleft of the mandible could undergo mandibular repair after puberty in conditions of a good occlusal relationship and normal maxillofacial development, even with mild masticatory dysfunction.

Coarse-to-Fine Satellite Images Change Detection Framework via Boundary-Aware Attentive Network.

Timely and accurate change detection on satellite images by using computer vision techniques has been attracting lots of research efforts in recent years. Existing approaches based on deep learning frameworks have achieved good performance for the task of change detection on satellite images. However, under the scenario of disjoint changed areas in various shapes on land surface, existing methods still have shortcomings in detecting all changed areas correctly and representing the changed areas boundary. To deal with these problems, we design a coarse-to-fine detection framework via a boundary-aware attentive network with a hybrid loss to detect the change in high resolution satellite images. Specifically, we first perform an attention guided encoder-decoder subnet to obtain the coarse change map of the bi-temporal image pairs, and then apply residual learning to obtain the refined change map. We also propose a hybrid loss to provide the supervision from pixel, patch, and map levels. Comprehensive experiments are conducted on two benchmark datasets: LEBEDEV and SZTAKI to verify the effectiveness of the proposed method and the experimental results show that our model achieves state-of-the-art performance.

Advancements in MAPK signaling pathways and MAPK-targeted therapies for ameloblastoma: A review.

Numerous signal transduction pathways are closely associated with the occurrence, development, and prognosis of ameloblastoma (AM). Mitogen-activated protein kinase (MAPK) is a serine/threonine-specific protein kinase that transduces intracellular signals in critical cellular phenomena. A number of recent analyses have reported that the MAPK signaling pathway contributes significantly to AM. High-throughput DNA sequencing methods, such as next-generation sequencing using Illumina have yielded advancements in studies on MAPK signaling pathways and their association with AM; in particular, BRAF V600E is mediated by the activation of the Ras/Raf/MAPK pathway. This review discusses advancements in studies on MAPK signaling pathways and MAPK-targeted inhibitors or antibodies, along with the merits and demerits of MAPK-targeted therapies, finally followed by a discussion regarding more efficient potential MAPK-targeted therapies to treat AM with few side effects, thereby providing novel insights into targeted therapy for AM.

Identification of SERPINE1, PLAU and ACTA1 as biomarkers of head and neck squamous cell carcinoma based on integrated bioinformatics analysis.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the six leading cancer by incidence worldwide. The 5-year survival rate of HNSCC patients remains less than 65% due to lack of symptoms in the early stage. Hence, biomarkers which can improve detection of HNSCC should improve clinical outcome. METHODS: Gene expression profiles (GSE6631, GSE58911) and the Cancer Genome Atlas (TCGA) HNSCC data were used for integrated bioinformatics analysis; the differentially expressed genes (DEGs) were then subjected to functional and pathway enrichment analysis, protein-protein interaction (PPI) network construction. Subsequently, module analysis of the PPI network was performed and overall survival (OS) analysis of hub genes in subnetwork was studied. Finally, immunohistochemistry was used to verify the selected markers. RESULTS: A total of 52 up-regulated and 80 down-regulated DEGs were identified, which were mainly associated with ECM-receptor interaction and focal adhesion signaling pathways. Importantly, a set of prognostic signatures including SERPINE1, PLAU and ACTA1 were screened from DEGs, which could predict OS in HNSCC patients from TCGA cohort. Experiment of clinical samples further successfully validated that these three signature genes were aberrantly expressed in the oral epithelial dysplasia and HNSCC, and correlated with aggressiveness of HNSCC patients. CONCLUSIONS: SERPINE1, PLAU and ACTA1 played important roles in regulating the initiation and progression of HNSCC, and could be identified as key biomarkers for precise diagnosis and prognosis of HNSCC, which will provide potential targets for clinical therapies.

Inhibition of autophagy augments chemotherapy in human salivary adenoid cystic carcinoma.

Although cisplatin (DDP)-based adjuvant chemotherapy is widely used in the treatment of salivary adenoid cystic carcinoma (SACC), SACCs have developed resistance to cisplatin, resulting in chemotherapy failure. Autophagy serves as a critical adaptive response, which was increased in tumor cells in chemotherapy. However, the function of autophagy is not clear in SACC. In this study, apoptosis induced by DDP in SACC high metastatic cell line (ACC-M) was revealed using MTT assay, flow cytometry, and caspase-3 immunoblotting. The autophagy activation induced by DDP treatment was measured by transmission electron microscopy, green fluorescent protein-light chain 3 plasmid transfection LC3 immunoblotting and p62 immunoblotting. 3-methyladenine (3-MA) or small interference RNA targeting beclin 1 (beclin 1 siRNA) inhibited autophagy and significantly enhanced DDP-induced apoptosis. ACC-M xenografts in nude mice further verified the synergistic effect of DDP and 3-MA. In conclusion, autophagy activation was caused to protect cancer cells from DDP-induced apoptosis and autophagy inhibition could be a promising strategy for adjuvant chemotherapy in SACC.

Prognostic Model and Nomogram for Early-Onset Adenoid Cystic Carcinoma of Head and Neck: A Retrospective SEER-Based Analysis.

BACKGROUND: Adenoid cystic carcinoma of head and neck (ACCHN) is an uncommon head and neck cancers, whose predilection age is 40 to 60. Some studies have revealed that early-onset cancers, such as colorectal cancers and esophageal adenocarcinoma, might present some unique clinicopathological features and have different prognosis with late-onset ones. However, little is known about the early-onset ACCHN. This study aimed to develop a prognostic nomogram for overall survival (OS) of patients younger than 40 with ACCHN. METHODS: Cases with ACCHN from 1975 to 2016 were retrieved from SEER-18 program. Demographic, clinical, and survival outcomes data of patients were identified for further analysis. The caret package was used to randomly divide early-onset patients into a training cohort and a validation cohort. A prognostic nomogram was constructed based on the univariate and multivariate Cox analysis. The discriminative ability and calibration power of the nomogram was evaluated by the concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve. RESULTS: A total of 5858 cases with ACCHN were selectively retrieved from SEER program in this study. The number of patients younger than 40, which was defined as early-onset ACCHN in this study, was 825. Based on the outcomes of multivariate analysis, tumor size, chemotherapy, surgery, and stage were selected for the construction of nomogram to predict 10-year OS. The C-index was 0.792 (95%CI 0.760-0.823) and 0.776 (95%CI 0.720-0.832) in the training and validation set, respectively. The area under the ROC curve values were 0.875 (95%CI 0.810-0.940) and 0.833(95%CI 0.754-0.912). The calibration plot indicated that this nomogram had proper calibration in both the training and validation cohorts. CONCLUSION: A novel prognostic nomogram for early-onset ACCHN was constructed and validated in this study. This nomogram could be applied for assisting clinicians to more accurately assess the prognosis of young patients, which might facilitate clinical decision-making and subsequent follow-up.

Prognosis of adenoid cystic carcinoma in head and neck region treated with different regimens-A single-centre study.

BACKGROUND: No study has evaluated the impact of regimen on recurrence, metastasis and survival in patients with adenoid cystic carcinoma (ACC). The present study aimed to compare the efficacy of radioactive seed implantation and other regimens in treating ACC, so as to investigate the clinical applicability of radioactive seed implantation and determine the indications for this regimen. METHODS: A total of 188 patients with ACC in oromaxillofacial region were allocated to four groups according to the treatment regimen: group 1 was treated with a combination of surgery and 125 I seed therapy, group 2 with a combination of surgery and external radiotherapy, group 3 with surgery, whereas group 4 was untreated. The Kaplan-Meier method was used to assess the survival rates, and the Cox regression analyses were used to identify the associated prognostic factors. RESULTS: The overall survival rates of 188 patients and groups 1, 2, 3 and 4 were 85.7%, 75%, 68.2% and 37.5%, respectively. Cox regression analysis revealed that age, T stage, N stage and regimen were independent prognostic factors of survival. Amongst patients with primary ACC, the efficacy of radioactive seed implantation was higher in those with perineural invasion than in those without. CONCLUSION: Patient age, T stage, N stage and regimen are independent prognostic factors of survival in patients with ACC. Patients treated with surgery combined with postoperative 125 I seed radiotherapy have a higher overall survival rate, and those with perineural invasion are more suitable for radioactive seed implantation therapy.

Attend to the Difference: Cross-Modality Person Re-Identification via Contrastive Correlation.

The problem of cross-modality person re-identification has been receiving increasing attention recently, due to its practical significance. Motivated by the fact that human usually attend to the difference when they compare two similar objects, we propose a dual-path cross-modality feature learning framework which preserves intrinsic spatial structures and attends to the difference of input cross-modality image pairs. Our framework is composed by two main components: a Dual-path Spatial-structure-preserving Common Space Network (DSCSN) and a Contrastive Correlation Network (CCN). The former embeds cross-modality images into a common 3D tensor space without losing spatial structures, while the latter extracts contrastive features by dynamically comparing input image pairs. Note that the representations generated for the input RGB and Infrared images are mutually dependant to each other. We conduct extensive experiments on two public available RGB-IR ReID datasets, SYSU-MM01 and RegDB, and our proposed method outperforms state-of-the-art algorithms by a large margin with both full and simplified evaluation modes.

Oral Microbiota Analysis of Tissue Pairs and Saliva Samples From Patients With Oral Squamous Cell Carcinoma - A Pilot Study.

Oral microbiota dysbiosis is associated with the occurrence and progression of oral cancer. To investigate the association between the microbiota and risk of oral squamous cell carcinoma (OSCC), we identified the microbial composition of paired tumor (TT)/normal paracancerous tissues (NPT) and saliva (TS) samples in OSCC patients through 16S rRNA gene sequencing. A total of 22 phyla, 321 genera, and 869 species were identified in the oral samples. Paired comparisons revealed significant differences between TT, NPT, and TS groups, with the genus Filifactor significantly enriched in TT. The phylum Actinobacteria; genus Veillonella; and species Granulicatella adiacens, Streptococcus sanguinis, and Veillonella rogosae were significantly enriched in NPT, while the phylum Bacteroidetes; genera Capnocytophaga, Haemophilus, and Prevotella; and seven species, including Capnocytophaga sp., Haemophilus sp., and Neisseria sp., were significantly enriched in TS. In TTs, the abundance of Prevotella intermedia was profoundly higher in the gingiva, while Capnocytophaga gingivalis and Rothia mucilaginosa were enriched in the lining mucosa and tongue. Increasing in abundance from the early tumor stage to the late stage, Solobacterium moorei in TT and Campylobacter sp. strain HMT 044 in TS were positively correlated with OSCC development, suggesting that bacteria were selected by different microenvironments. The correlation between 11 microbial species and 17 pathway abundances was revealed, indicating the potential function of low-abundance bacteria. Overall, our analysis revealed that multiple oral bacterial taxa are associated with a subsequent risk of OSCC and may be used as biomarkers for risk prediction and intervention in oral cancers.

Evaluation of an improved anchoring nail in temporomandibular joint disc repositioning surgery: A prospective study of 25 patients.

To confirm the effectiveness and stability of an improved anchoring nail through a prospective study using clinical evaluation and magnetic resonance imaging (MRI). Patients undergoing TMJ disc reduction and fixation were followed up for 1 year.Visual analog scale (VAS) pain scores and TMJ range of motion (maximum interincisal opening, protrusive excursion, lateral excursion) data were gathered pre- and postoperatively, and patient satisfaction was recorded. Four time points were investigated: before surgery (T0), 1 month post-surgery (T1), 6 months post-surgery (T2), and 1 year post-surgery (T3). Twenty-five patients (50 joints) participated in the study. The overall success rates of the improved and traditional anchoring nails were 88% and 92%, respectively. One year post-surgery, the patients' TMJ motion improved significantly (p < 0.001), and their pain was significantly alleviated (p < 0.001). Condyle height did not change significantly within 6 months (p = 0.801), but had increased by approximately 1.35 mm (p < 0.001) at 1 year post-surgery. The MRI scans also confirmed that new bone mass growth was present 1 year post-surgery. Compared with the traditional anchoring nail, the improved anchoring nail had a similar success rate and was associated with fewer foreign body sensations and less pain. Its clinical application should be further tested in studies with longer follow-up times and larger sample sizes.

MiR-21-5p regulates extracellular matrix degradation and angiogenesis in TMJOA by targeting Spry1.

BACKGROUND: Due to the lack of research on the pathological mechanism of temporomandibular joint osteoarthritis (TMJOA), there are few effective treatment measures in the clinic. In recent years, microRNAs (miRs) have been demonstrated to play an important role in the pathogenesis of osteoarthritis (OA) by regulating a variety of target genes, and the latest evidence shows that miR-21-5p is specifically overexpressed in OA. The purpose of this project was to clarify whether miR-21-5p can regulate the TMJOA process by targeting Spry1. METHODS: TMJOA was induced by a unilateral anterior crossbite (UAC) model, and the effect of miR-21-5p knockout on TMJOA was evaluated by toluidine blue (TB), immunohistochemical (IHC) staining, Western blotting (WB) and RT-qPCR. Primary mouse condylar chondrocytes (MCCs) were isolated, cultured and transfected with a series of mimics, inhibitors, siRNA-Spry1 or cDNA Spry1. WB, RT-qPCR, IHC and TB were used to detect the effect of miR-21-5p and its target gene Spry1 on the expression of MMP-13, VEGF and p-ERK1/2 in TMJOA. The effect of miR-21-5p on angiogenesis was evaluated by chick embryo chorioallantoic membrane (CAM) assay and WB. RESULTS: In the UAC model, the cartilage thickness and extracellular matrix of miR-21-5p knockout mice were less damaged, and miR-21-5p and UAC model were shown to affect the expression of Spry1, IL-1ß, MMP-13, and VEGF. Luciferase experiments confirmed that Spry1 was the direct target of miR-21-5p. The expression levels of Spry1, MMP-13, VEGF and p-ERK1/2 in MCCs transfected with miR-21-5p mimic were higher than those in the inhibitor group. Under the simulated inflammatory environment of IL-1ß, the expression levels of MMP-13, VEGF and p-ERK1/2 were positively correlated with miR-21-5p, while Spry1 was negatively correlated with miR-21-5p. Inhibition of miR-21-5p expression and overexpression of Spry1 enhanced the inhibition of MMP-13, VEGF and p-ERK1/2 expression. MiR-21-5p had a significant role in promoting angiogenesis in the chick embryo CAM assay, and this role was clearly mediated by the ERK-MAPK signalling pathway. CONCLUSION: This study verified that miR-21-5p can promote the process of TMJOA by targeting Spry1, which provides a new direction for future research on the treatment of this disease.

Joint cavity injection combined with manual reduction and stabilization splint treatment of anterior disc displacement.

AIM: This study aimed to compare the clinical efficacy of upper and lower joint cavity treatment (UJCT vs. LJCT) in patients with anterior disc displacement without reduction (ADDw/oR) of temporomandibular joint (TMJ). MATERIAL AND METHODS: A total of 56 patients with unilateral ADDw/oR were randomly divided into two groups: UJCT group and LJCT group. Manual reduction was done in all the patients after joint cavity rejection of sodium hyaluronate. Then, they were treated with stabilization splint for one or two months. At last, Friction index was calculated to evaluate the therapeutic efficacy at 6 to 12 months follow-up. RESULTS: The maximal mouth-opening degrees in the both groups increased significantly when compared with pre-treatment group (P < 0.01), and the Friction index decreased significantly when compared with pre-treatment group (P < 0.01); In LJCT group, the degrees of maximal mouth-opening increased significantly as compared to UJCT group (P < 0.05), and Friction index were also markedly lower than that in UJCT group (P < 0.05). CONCLUSION: In the patients with ADDw/oR of TMJ, the clinical efficacy of LJCT is superior to that of UJCT, especially in the TMJ pain relief, mouth-opening degree and mandibular movement improvement.

Expression of BNIP3 and its correlations to hypoxia-induced autophagy and clinicopathological features in salivary adenoid cystic carcinoma.

BACKGROUND: The expression of Bcl-2/adenovirus E1B 19 kDa-interacting protein3 (BNIP3) has been explored in many human malignancies, but not in adenoid cystic carcinoma (ACC). OBJECTIVE: This study investigated the clinical significance of expression of BNIP3 in ACC tissues and cells and elucidated its correlations to hypoxia-induced autophagy. METHODS: Immunohistochemical and immunofluorescence staining were used to explore BNIP3, HIF-1α and LC3 expression. RESULTS: BNIP3 was positively expressed in 41 cases (63.1%), and was significantly correlated with histological grade (P= 0.001). HIF-1α was positively expressed in 52 cases (80.0%) and was significantly correlated with TNM stage (P= 0.023) and histological grade (P= 0.024). LC3 was positively expressed in 37 cases (56.9%) and was significantly correlated with TNM stage (P= 0.019). The expression of BNIP3 was correlated with HIF-1α expression (P= 0.011). The overall survival in the negative BNIP3 expression group tended to be better than in the positive BNIP3 expression (P= 0.011). In vitro experiment, BNIP3 immunofluorescence staining was detected in cells treated with CoCl2 (for hypoxic condition). CONCLUSIONS: The data indicated that BNIP3 plays a vital role in the tumorigenesis of adenoid cystic carcinoma and could be a new target for gene therapy of adenoid cystic carcinoma.

Expression of RECK and MMP-2 in salivary adenoid cystic carcinoma: Correlation with tumor progression and patient prognosis.

Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a glycosylphosphatidylinositol-anchored glycoprotein, inhibits the enzymatic activities of certain matrix metalloproteinases (MMPs). RECK has been studied in numerous human tumors, but the expression of RECK in salivary adenoid cystic carcinoma (SACC), and its correlation with patient prognosis, has never been investigated thus far. In the present study, the expression of RECK and MMP-2 was evaluated in two ACC cell lines and in 83 patients with SACC. The results of quantitative polymerase chain reaction and western blot analysis revealed that the ACC-2 and ACC-M cell lines expressed RECK and MMP-2 mRNA and protein. The immunohistochemical staining in the patients demonstrated that positive expression of RECK and MMP-2 was observed in 21/83 (25.3%) and 69/83 (83.1%) cases, respectively, and that RECK expression was significantly associated with the tumor-node-metastasis stage, histological grade and perineural invasion of patients with SACC (P<0.05). Furthermore, there was a significant association between the positive expression of RECK and that of MMP-2 (P<0.0001). Univariate and multivariate analyses confirmed that a lack of RECK expression was an independent and significant factor for the prediction of a poor prognosis. In conclusion, RECK is a promising prognostic marker and potential therapeutic agent in SACC.

[Expression and clinical significance of p53 and autophagy-related gene Beclin1 in salivary pleomorphic adenoma and carcinoma in pleomorphic adenoma].

PURPOSE: To investigate the expression of p53 and Beclin1 in salivary pleomorphic adenoma (PA) and its clinical significance. METHODS: The expression of p53 and Beclin1 were assessed by immunohistochemistry in 108 cases of PA and 20 cases of carcinoma in pleomorphic adenoma(CIPA). The results were used to analyze the relationship between gene expressions and the development of PA as well as the clinical pathological features. Statistic analysis was conducted with SPSS 20.0 software package. RESULTS: The positive expressions of p53 in PA samples (9%) were significantly lower than that in CIPA(14%) (P<0.001). The positive expressions of autophagy-related gene Beclin1 in PA samples(91%) were significantly higher than that CIPA (11%) (P<0.001). The expression levels of these genes were not associated with gender, age, clinical course, tumor size, and location of PA(P>0.05). There was a negative correlation between p53 and Beclin1 expression in PA (r=-0.330,P<0.05). CONCLUSIONS: The expression levels of Beclin1 and p53 protein are closely related to the development of PA. Reduced autophagy and enhanced anti apoptosis coexist in the process of tumor formation. Thus, raising the autophagy ability may become another alternative choice for cancer therapy.

Suppression of NF-κB activity by mutant IκBα: A molecular target for radiosensitization of adenoid cystic carcinoma.

The constitutive activation of the nuclear factor κB (NF-κB) signaling pathway is involved in oncogenesis, invasive growth, metastasis and induced resistance to radiation and chemotherapy. Selective inhibition of the NF-κB signaling pathway, either by a mutant inhibitor or pharmacological agents, improves the therapeutic efficiency of irradiation. In the present study, the changes in NF-κB expression and the rate of apoptosis were investigated following irradiation of cells of an adenoid cystic carcinoma cell line (ACC-M) in which NF-κB expression had been inhibited by transient transfection with a mutant IκBα plasmid. ACC-M cells were transiently transfected with the mutant IκBα plasmid using Lipofectamine and the expression of this mutant IκBα gene was verified. The presence of the mutant IκBα gene alone did not result in a reduction in cell proliferation. Furthermore, a significant inhibition of translocation and synthesis of NF-κB protein in the transfected cells was observed after irradiation. NF-κB protein was activated by different doses of irradiation in a dose- and time-dependent manner with concordant changes in the radiosensitivity of ACC-M cells. We conclude that the mutant IκBα gene selectively inhibited the NF-κB pathway, which may be a promising method to improve the radiosensitivity of adenoid cystic carcinomas.

Expression of autophagy and ER stress-related proteins in primary salivary adenoid cystic carcinoma.

Autophagy is the endogenous cellular pathway that facilitates cellular survival by maintaining energy homeostasis and macromolecular synthesis during cellular stress and nutrient deprivation. Endoplasmic reticulum (ER) stress is the process in which disruption of these physiological functions leads to an accumulation of unfolded proteins and induces the unfolded protein response (UPR). ER stress and autophagy are involved in human cancer. We investigated the expression of autophagic proteins (LC3 and beclin 1) and ER stress-related protein (GRP78) in head and neck adenoid cystic carcinoma tissue. Tissue samples from 79 cases of head and neck adenoid cystic carcinoma tissue were utilized for immunohistochemistry. LC3 expression was significantly correlated with lymph node involvement (P=.016) and TNM (P=.021). Beclin 1 expression was significantly correlated with the histological growth pattern (P=.002), the histological grade (P=.000), and longer survival (P=.000). GRP78 expression was significantly correlated with the histological growth pattern (P=.019), the histological grade (P=.019), and longer survival (P=.001). LC3 expression was positively correlated with beclin 1 expression (P=.000); LC3 and beclin 1 expressions were positively correlated with GRP78 expression respectively (P=.035) (P=.008). Our study describes the expression of LC3, beclin 1, and GRP78 in adenoid cystic carcinoma and its relationship with clinicopathologic factors and overall survival. These results suggest that LC3, beclin 1, and GRP78 may play an important role in the tumorigenesis of adenoid cystic carcinoma, and that beclin 1 and GRP78 may serve as new prognostic indicators for the outcome of patients with adenoid cystic carcinoma.

Protecting the oral mucosa in patients with oral tongue squamous cell carcinoma treated postoperatively with intensity-modulated radiotherapy: a randomized study.

OBJECTIVES/HYPOTHESIS: Is the severity of acute oral mucositis in patients who receive postoperative intensity-modulated radiotherapy (PO-IMRT) for oral tongue squamous cell carcinoma (SCC) reduced by sparing the oral mucosa outside of the planning target volume (PTV)? STUDY DESIGN: Prospective, randomized trial. METHODS: Forty-eight patients with oral tongue SCC who received PO-IMRT at our institution were randomized to two groups: the oral-sparing (OR-SP) group and oral-unsparing (OR-USP) group. For the OR-SP group (n = 24), the oral mucosa outside of the PTV was spared. Furthermore, the mucosa including the bilateral cheeks, upper lip, and lower lip was defined as the united site and given <32 Gy. For the OR-USP group (n = 24), none of the oral mucosa was protected. The severity of clinical acute mucositis in each patient was assessed weekly during PO-IMRT until completely healed. Oral mucositis was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Dosimetry and therapeutic measures related to acute mucositis between the two groups were compared. RESULTS: During PO-IMRT, no patient experienced grade 4+ acute mucositis in any oral site. Compared to the OR-USP group, there was less grade 2 and 3 mucositis in the united site of the OR-SP group (0% and 25% vs. 45.8% and 54.2%, respectively; P = .000). Also, the mean dose to the united site was significantly lower with OR-SP compared to OR-USP (41.8 ± 7.4 Gy vs. 58.8 ± 2.2 Gy; P = .000). The OR-SP group was associated with significant reductions in the use of analgesics (P = .043) and intravenous antibiotics (P = .039). No recurrences were detected in the vicinity of the spared oral mucosa (the united site) during a median follow-up time of 30 months. CONCLUSIONS: OR-SP PO-IMRT for patients with oral tongue SCC resulted in a significant decrease in the severity of acute mucositis and improved quality of life. The sparing of the oral mucosa outside of the PTV is safe and does not compromise oncologic outcomes.