Japanese Clinical Practice Guideline for Head and Neck Cancer.

OBJECTIVE: The first revision of "Japanese Clinical Practice Guideline for Head and Neck Cancer" was made in 2013 by the clinical practice guideline committee of Japan Society for Head and Neck Cancer, in response to the revision of the TNM classification. METHODS: 34 CQs (Clinical Questions) were newly adopted to describe the diagnosis and treatment methods currently considered most appropriate, and offered recommendation grade made by the consensus of the committee. A comprehensive literature search was performed for studies published between 2001 and 2012 using PubMed. Qualified studies were analyzed and the results were evaluated, consolidated and codified by all the committee members. RESULTS: Elective neck dissection (ND) does contribute to improvement in survival and should be performed for patients with high-risk tongue cancer. At present, no research has clearly demonstrated the utility of superselective arterial infusion chemotherapy. However, depending on the site and stage of the cancer, combination with radiotherapy may be useful for preserving organ function or improving survival rate. Concurrent CDDP chemotherapy and adjuvant radiotherapy contributes to improvement of survival rate as an adjuvant therapy for advanced squamous cell carcinoma of the head and neck in patients at high risk of recurrence. The anti-EGFR antibody cetuximab (Cmab) has an additive effect with radiotherapy. However, the indication must be carefully considered since this treatment has not been compared with the standard treatment of chemoradiotherapy. Cmab has been shown to have an additive effect with chemotherapy (CDDP/5-FU) in patients with unresectable metastatic or recurrent cancer. Preoperative and postoperative oral care may reduce the risk of postoperative complications such as surgical wound infection and pneumonia in head and neck cancers. Rehabilitation soon after ND for cervical lymph node metastasis is recommended for maintaining and restoring shoulder function. CONCLUSIONS: In this article, we described most relevant guidelines and CQs for the diagnosis and treatment of head and neck cancer in Japan. These guidelines are not intended to govern therapies that are not shown here, but rather aim to be used as a guide in searching for the most appropriate treatment for individual patient.

MRI changes in the temporomandibular joint following mandibular setback surgery using sagittal split ramus osteotomy with rigid fixation.

OBJECTIVES: This study examined the changes in temporomandibular joint dysfunction (TMD) symptoms and investigated the variations in the disc position, disc and condylar morphology following sagittal split ramus osteotomy (SSRO) with rigid fixation in patients with mandibular prognathism. Furthermore, the authors examined the correlation between mandibular setback and TMD symptoms. METHODS: The study included 24 Japanese patients with jaw deformities who were treated using bilateral SSRO and Le Fort I osteotomy. The clinical and magnetic resonance imaging findings in the temporomandibular joint were evaluated preoperatively and at three and six months postoperatively. RESULTS: The preoperative TMD symptoms were significantly associated with the prevalence of TMD symptoms at six months postoperatively. Anterior disc displacement improved in four joints with slight displacement and with no morphological change. There were no postoperative changes in condylar morphology. There was no significant correlation between mandibular setback and the postoperative TMD symptoms. CONCLUSION: Postoperative TMD symptoms may be influenced mainly by preoperative TMD symptoms rather than mandibular setback using SSRO with rigid fixation. Therefore, patients with TMD symptoms require physical examination and MRI for appropriate diagnosis preoperatively.

Symmetric Lipomatosis Arising in the Tongue Presenting as Macroglossia and Articulatory Disorder.

Symmetric lipomatosis is definitively characterized by symmetric, tumorous lipomatous proliferation of adipose tissue that often develops in the head and neck, shoulders, and upper trunk. However, in the oral region, symmetric lipomatosis of the tongue (SLT) is an extremely rare condition related to generalized lipidosis that is often caused by chronic alcoholism. It is characterized by multiple symmetric lipomatous nodules and diffuse bilateral swelling located within the tongue. We report an extremely rare case of SLT arising in an 80-year-old man with a long history of alcoholic liver cirrhosis. He exhibited multiple soft nodular protrusions on the bilateral margin of the tongue presenting as macroglossia for years. Although MR imaging showed multiple fatty masses on both sides of the tongue, there was no elevated tumor mass on the bilateral margin. The patient underwent bilateral partial glossectomy under general anesthesia. Histopathologically, the resected tumor exhibited diffuse infiltration with mature adipose tissue lacking a fibrous capsule. Due to the lipidosis and the unusual presentation of multiple lesions, the lesion was ultimately diagnosed as SLT. At present, after surgery, the patient wears a full-denture and is in excellent condition, with no sign of recurrence, improved QOL, and recovery of masticatory, articulatory, and speech intelligibility functions.

Comparison of magnesium alloys and poly-l-lactide screws as degradable implants in a canine fracture model.

The aims of this study were to evaluate in vivo the biological responses to implants composed of biodegradable anodized WE43 (containing magnesium yttrium, rare earth elements and zirconium; Elektron SynerMag®) magnesium alloy, monolithic WE43 magnesium alloy and poly-l-lactic acid (PLLA), which are commonly used materials in clinic settings, and to evaluate the effectiveness of the materials as bone screws. The effectiveness of the magnesium alloy implants in osteosynthesis was evaluated using a bone fracture model involving the tibia of beagle dogs. For the monolithic WE43 implants, radiological, and histological evaluation revealed that bone trabeculae around the implanted monolithic WE43 decreased because of an inflammatory response. However, there was no damage due to hydrogen gas or inflammatory response in the bone tissue around the anodized WE43 implants. After 4 weeks, all the PLLA implants (n = 3) had broken but the WE43 implants had not (n = 6). These results suggest that the WE43 implants had sufficient strength to fix bone fractures at load-bearing sites in orthopedic and oral maxillofacial surgery. Therefore, these biodegradable magnesium alloys are good candidates for replacing biodegradable polymers. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1282-1289, 2016.

Massive odontoameloblastoma arising in the maxilla: a case report.

INTRODUCTION: Odontoameloblastoma is an extremely rare mixed odontogenic tumor with both epithelial and mesenchymal components. The term odontoameloblastoma first appeared in the 1971 World Health Organization classification (Pindborg JJ., et al.) and is defined as "a neoplasm that includes odontogenic ectomesenchyme in addition to odontogenic epithelium that resembles an ameloblastoma in both structures and behavior." Because of the aggressive nature and risk of recurrence of the tumor, complete resection is essential. In this report, we describe an extremely rare case of a patient with massive odontoameloblastoma arising in the maxilla and occupying maxillary sinus. CASE PRESENTATION: In 2013, an 11-year-old Japanese boy was referred to our department for a painless and large mass of the right maxillary region. A panoramic X-ray showed a unilocular cystic lesion in the right maxilla containing a calcified mass in the lesion associated with an impacted tooth. Computed tomography showed a cystic lesion that included calcified structures and measured 3.6×3.1×2.7 cm. In 2013, the patient underwent tumor extirpation combined with impacted tooth extraction. The histopathological diagnosis was an odontoameloblastoma. No recurrence was noted 27 months after the operation. CONCLUSIONS: The patient has undergone postoperative occlusal guidance and functional orthodontic treatment, and his postoperative condition is excellent. However, postoperative recurrence or malignant transformation can occur in cases of odontoameloblastoma, and close long-term follow-up will be continued for our patient.

Simultaneous Detection of Both Single Nucleotide Variations and Copy Number Alterations by Next-Generation Sequencing in Gorlin Syndrome.

Gorlin syndrome (GS) is an autosomal dominant disorder that predisposes affected individuals to developmental defects and tumorigenesis, and caused mainly by heterozygous germline PTCH1 mutations. Despite exhaustive analysis, PTCH1 mutations are often unidentifiable in some patients; the failure to detect mutations is presumably because of mutations occurred in other causative genes or outside of analyzed regions of PTCH1, or copy number alterations (CNAs). In this study, we subjected a cohort of GS-affected individuals from six unrelated families to next-generation sequencing (NGS) analysis for the combined screening of causative alterations in Hedgehog signaling pathway-related genes. Specific single nucleotide variations (SNVs) of PTCH1 causing inferred amino acid changes were identified in four families (seven affected individuals), whereas CNAs within or around PTCH1 were found in two families in whom possible causative SNVs were not detected. Through a targeted resequencing of all coding exons, as well as simultaneous evaluation of copy number status using the alignment map files obtained via NGS, we found that GS phenotypes could be explained by PTCH1 mutations or deletions in all affected patients. Because it is advisable to evaluate CNAs of candidate causative genes in point mutation-negative cases, NGS methodology appears to be useful for improving molecular diagnosis through the simultaneous detection of both SNVs and CNAs in the targeted genes/regions.

Massive Neurilemoma of the Hard Plate in Which Preoperative Diagnosis Was Difficult.

The patient was an 84-year-old man who was referred to our hospital in mid-December 2012 for a close examination of a mass arising from the left side of the hard palate that was found by a local dentist. The initial examination revealed the presence of a 3.0-cm elastic soft, dome-shaped mass in the left hard palate. CE-CT showed a lesion of size 1.8 × 1.4 cm in the right hard palate, which extended upward and invaded the nasal cavity. The mass was a solid tumor associated with resorption of surrounding bone and expansion of the greater palatine canal. CE-MRI indicated that the mass extended upward and invaded the nasal cavity, and the mass showed hypointensity on T1-weighted images, hyperintensity on T2-weighted images, and an irregular margin with internal enhancement. Abnormal uptake of FDG on PET-CT (SUVmax = 5.2) was observed in the left hard palate. The biopsy site lesion rapidly increased in size and biopsy was performed again in January 2013 due to suspicion of a malignant tumor. The histopathological diagnosis was a suspected malignant neurogenic tumor. Therefore, the patient underwent partial maxillectomy and a split-thickness skin graft in late February 2013. No recurrence was noted 29 months after the operation.

Chronic Sclerosing Sialadenitis of the Submandibular Gland as the Initial Symptom of IgG4-Related Disease: A Case Report.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic condition accompanied by tumefactive lesions, dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis in various organs, and, frequently, elevated serum IgG4 levels. Chronic sclerosing sialadenitis (also termed Küttner's tumor) is thought to be a lesion of IgG4-RD; thus, IgG4-related sialadenitis may be the initial symptom of IgG4-RD. We herein report a 64-year-old Japanese female with IgG4-related chronic sclerosing sialadenitis of the right submandibular gland and retroperitoneal fibrosis, who subsequently developed tubulointerstitial nephritis and pancreatitis. She was referred to our Department for treatment of swelling of the right submandibular gland; preoperative imaging studies suggested a malignant tumor. We extirpated the submandibular glands bilaterally and diagnosed IgG4-related chronic sclerosing sialadenitis pathologically. Subsequently, the patient's serum IgG4 concentration increased, and lesions in the retroperitoneum, kidney, and pancreas were confirmed by imaging. Although the radiological characteristics of these lesions mimicked malignancy, steroid treatment was commenced based on the pathology of the submandibular gland and elevated serum IgG4 level. This caused the lesions to disappear, indicating that the patient had experienced IgG4-related retroperitoneal fibrosis, tubulointerstitial nephritis, and pancreatitis. No relapse was detected for 4 years 8 months after surgery. A pathological diagnosis is crucial to exclude the possibility of malignancy and to make treatment decisions when lesions are evident in other organs. In addition, periodic evaluation of the serum IgG4 concentration and imaging of the whole body are warranted in long-term follow-up.

Clinical characteristics of multiple primary carcinomas of the oral cavity.

OBJECTIVES: This study aimed to clarify the clinical characteristics of multiple primary carcinomas of the oral cavity. MATERIALS AND METHODS: We retrospectively reviewed the cases of 1015 patients who were treated during follow up for oral cancer at Tokyo Medical and Dental University between March 2001 and December 2012. We compared the clinical characteristics of 961 patients who developed single primary oral squamous cell carcinoma (SCC) during follow up and 54 patients who subsequently developed multiple primary carcinomas in the oral cavity. RESULTS: Mean age at first diagnosis was significantly higher in patients with multiple primary carcinomas than single primary carcinoma. Multiple primary carcinomas showed a female predilection, were most prevalent in the gingiva, and tended to show earlier tumor and nodal stages than single primary carcinoma. The local recurrence rate was higher for multiple primary carcinomas than single primary carcinoma, and it increased with the number of multiple primary occurrences. The disease-specific survival rate at 10 years for patients with single primary carcinoma was 85.3% and that for patients with multiple primary carcinomas was 79.6%. The cumulative incidence rate for metachronous second multiple primary carcinomas after the onset of first carcinoma at 10 years was 8.0%. The recurrence of multiple primary carcinomas did not decrease the survival rate. CONCLUSION: Differences were found in the clinical characteristics between patients with single oral SCC and those with multiple primary oral carcinomas. Early diagnosis and treatment as well as close long-term follow up are needed for patients with multiple primary oral carcinomas.

Functional outcomes with dental prosthesis following simultaneous mandibulectomy and mandibular bone reconstruction.

PURPOSE: This study sought to ascertain masticatory outcomes in patients who underwent mandibulectomy or hemimandibulectomy together with mandibular bone reconstruction to allow for placement of a removable dental prosthesis. METHODS: Perioperative changes in masticatory performance, masticatory ability for solids, and patients' subjective satisfaction were evaluated for 101 patients who had mandibulectomy immediately followed by bone reconstruction. Differences in masticatory performance and masticatory ability for solids after surgery were determined according to occlusal support after surgery and whether the patient was wearing a removable dental prosthesis or not. Occlusal support areas were classified according to Eichner's classification. RESULTS: Preoperative Eichner's class A patients had no experience of wearing a dental prosthesis before surgery and after surgery did not want one. Their masticatory performance was better than that of patients who wanted a dental prosthesis after surgery. Retrospective analysis of postoperative Class B and C patients revealed that masticatory performance was lower in those who wanted a dental prosthesis than in those who did not want one. When patients wore a dental prosthesis after surgery, masticatory performance was markedly improved over not wearing it. All patients' subjective satisfaction was significantly improved after surgery. CONCLUSIONS: Increasing the number of occlusal support areas by wearing a removable dental prosthesis after simultaneous mandibulectomy or hemimandibulectomy and mandibular bone reconstruction may improve masticatory functions. Those professional involved in the rehabilitation for the mandibular defect should be mindful that masticatory functions after such surgeries were affected by the masticatory functions before surgery and the number of occlusal support areas after surgery.

Temporomandibular joint intermittent closed lock: clinic and magnetic resonance imaging findings.

OBJECTIVE: This study was carried out to describe the clinical and magnetic resonance imaging (MRI) findings of patients with intermittent closed lock (ICL) of the temporomandibular joint (TMJ). STUDY DESIGN: This retrospective study included 58 joints with ICL and 526 joints without ICL as controls. We compared the MRI findings between the patients with and without ICL and investigated clinical and MRI finding of ICL patients. We divided ICL patients into 2 groups based on the treatment efficacy: effective and ineffective. RESULTS: There were significant differences in the prevalence of disk deformity between the joints with and without ICL. Masticatory muscle pain was observed in 41.7% of the effective group and in 80% of the ineffective group, respectively. CONCLUSIONS: These results suggest that there is a relationship among the onset of ICL and disk deformation. Masticatory musclepain was significantly observed in the ineffective group.

Lack of association between high-risk human papillomaviruses and oral squamous cell carcinoma in young Japanese patients.

BACKGROUND: Human papillomaviruses (HPV) may play an important role as one of the possible etiologies of oral squamous cell carcinoma (OSCC). The present study aimed to investigate the association between HPV and OSCC in young Japanese patients by examining the presence of HPV DNA and surrogate markers in OSCC tissues. MATERIALS AND METHODS: Forty young patients with OSCC whose surgical specimens were available were analyzed and compared with 40 patients randomly recruited from a pool of patients aged >40 years. HPV DNA was detected using the polymerase chain reaction-based AMPLICOR(®) HPV test, and surrogate markers of HPV infection were analyzed using immunohistochemical techniques to detect p16(INK4a) and p53. RESULTS: Only two (5%) young patients and one (2.5%) older patient were positive for HPV DNA. p16(INK4a) overexpression was identified in six (15%) young patients. p53 staining levels were not high in tissues of most young patients (27 patients, 67.5%). HPV DNA status did not significantly correlate with p16(INK4a) expression levels. Profiles of increased levels of p16(INK4a) expression with diminished levels of p53 staining were not associated with the presence of HPV DNA. The combined p53 with p16(INK4a) profiles were significantly correlated with alcohol consumption in younger patients (p=0.006). CONCLUSIONS: RESULTS of the present study indicate that HPV is less likely to cause OSCC in young Japanese patients, and the p16(INK4a) expression level is not an appropriate surrogate marker for HPV infection in OSCC.

Methotrexate-associated lymphoproliferative disorder arising in the retromolar triangle and lung of a patient with rheumatoid arthritis.

We report an extremely rare case of massive methotrexate-associated lymphoproliferative disorder (MTX-LPD) arising in the retromolar triangle and lung of a patient with rheumatoid arthritis. The patient was a 75-year-old woman who was referred to our department because of severe pain associated with a unilateral ulcer on the left retromolar triangle. The tumor had an extranodal location in the retromolar triangle and in the right lung. A clinicopathologic examination found a lymphocytic infiltrate with increasingly atypical histopathologic features. Atypical large cells were strongly positive in Epstein-Barr virus-encoded small RNA in situ hybridization and in staining with CD20 antibodies. MTX-LPD was diagnosed based on the medical history and histopathologic results. The lesion responded well to withdrawal of MTX followed by R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. There have been no signs of recurrence for 4 years since withdrawal of MTX.

Gelatin hydrogel as a carrier of recombinant human fibroblast growth factor-2 during rat mandibular distraction.

PURPOSE: The aim of the present study was to evaluate the feasibility of a gelatin hydrogel system to enhance recombinant human fibroblast growth factor-2 (rhFGF-2)-induced osteogenic effects during rat mandibular distraction. MATERIALS AND METHODS: Mandibular distraction was performed in 28 male Wistar rats. Then, the rats were divided into 5 groups in which the designated gel mix was inserted into the distracted area: group 1, rhFGF-2 alone (n = 5); group 2, collagen alone (n = 6); group 3, collagen incorporating rhFGF-2 (n = 6); group 4, gelatin hydrogel alone (n = 5); and group 5, gelatin hydrogel incorporating rhFGF-2 (n = 6). The mandibles were excised 29 days after surgery and the newly formed bone was analyzed radiologically and histologically. The experimental groups were compared using the Fisher post hoc test (95% statistical significance threshold; P < .05). RESULTS: Peripheral quantitative computed tomographic analysis, von Kossa staining, and calcein staining showed that using gelatin hydrogel with rhFGF-2 (group 5) significantly increased cortical bone mineral density, the domain area of hard tissue, the domain area of cortical bone area, total bone mineral content, cortical bone mineral content, the von Kossa-stained area, and the calcein-stained area compared with the collagen carrier (group 3). Group 5 also had a significantly larger number of cells positive for tartrate-resistant acid phosphatase compared with group 3 and radiopaque areas were observed more frequently. CONCLUSIONS: The present findings suggest that gelatin hydrogel is a feasible delivery system for rhFGF-2, and when used together perform better in regard to hard tissue healing and treatment time after surgery.

Current status of oral cancer treatment strategies: surgical treatments for oral squamous cell carcinoma.

The primary treatment modality of oral cancer is generally determined according to the stage of the disease, with surgical treatment remaining the mainstay of multimodal treatment. When selecting the treatment, many factors are taken into consideration, and the treatment should be tailored individually to the patient's needs and consider the quality of life as well as the survival of the patient. Early-stage disease is primarily managed with surgery or brachytherapy without functional morbidity, whereas for advanced-stage disease multidisciplinary treatment is recommended, not only for enhanced survival but also for improved quality of life. After resection of large primary tumors, reconstructive surgery is required. Free tissue transfer currently represents one of the most popular and reliable techniques for oral reconstruction. For cN0 neck, elective neck dissection is recommended when the risk of occult metastases is >20 %, when the neck is entered either for resection of the primary tumor or for reconstruction, or when the patient is unlikely to return for a close follow-up. Sentinel node biopsy is performed investigationally. Modified radical neck dissection is the gold standard for cN+ neck. For patients with multiple node metastases or extracapsular spread, postoperative radiotherapy or chemoradiotherapy is recommended, with the lymph nodes situated outside the confines of the radical neck dissection, such as the lingual and retropharyngeal nodes, receiving considerable attention. Targeted therapy for oral cancer is still a relatively new concept, and more studies are needed to confirm the clinical effectiveness of these drugs.

A case of Basal cell adenoma of the upper lip.

Basal cell adenoma is a rare type of benign salivary gland tumor found most commonly in the parotid gland. We present a rare case of basal cell adenoma arising in the minor salivary gland of the upper lip. The patient was a 59-year-old Japanese man who visited our department in December 2012 with a chief complaint of a mass in the upper lip, which had increased in size over several years. A mobile, elastic, and relatively soft mass without tenderness was palpable in the upper lip region. The mucosa of the upper lip covering the mass was normal. Tumor extirpation was performed under local anesthesia. Histologically, the tumor had a capsule and was composed of islands of relatively uniform, monotonous cells. Immunohistochemically, the inner tumor comprised tubuloductal structures that showed strong staining for CK7, while the outer tumor showed weak staining for CK7. The outer tumor cells also stained positively for CD10 and p63. The MIB-1 (Ki-67) labeling index was extremely low. Basal cell adenoma was diagnosed based on these results. The postoperative course was uneventful 12 months after surgery and there has been no recurrence.

Migration linked to FUCCI-indicated cell cycle is controlled by PTH and mechanical stress.

Bone metabolism is maintained via balanced repetition of bone resorption by osteoclasts and bone formation by osteoblasts. Osteoblastic cells are capable of conducting self-renewal and differentiation that are basically associated with cell-cycle transition to enable cell specification and bone formation. Osteoblasts are also migrating to fill the resorption cavity curved by osteoclasts during bone remodeling to maintain homeostasis of bone mass whose imbalance leads to osteoporosis. However, technical difficulties have hampered the research on the dynamic relationship between cell cycle and migration in osteoblasts. In this report, we overcome these problems by introducing fluorescent ubiquitination-based cell cycle indicator (FUCCI) reporter system in calvarial osteoblastic cells and reveal that the cells in G1 as well as S/G2 /M phase are migrating. Furthermore, the osteoblastic cells in S/G2 /M phase migrate faster than those in G1 phase. Interestingly, parathyroid hormone (PTH) as an anabolic agent enhances migration velocity of the cells. Mechanical stress, another anabolic signal, also enhances migration velocity. In contrast, in the presence of both PTH and mechanical stress, the migration velocity returns to the base line levels revealing the interaction between the two anabolic stimuli in the regulation of cell migration. Importantly, PTH and mechanical stress also interact when they regulate the transition of cell cycle. These data demonstrate that osteoblastic migration is linked to cell cycle and it is under the control of mechanical and chemical stimuli that coordinate to regulate bone mass.

Galectin-7 as a potential predictive marker of chemo- and/or radio-therapy resistance in oral squamous cell carcinoma.

Treatment of advanced oral squamous cell carcinoma (OSCC) requires the integration of multimodal approaches. The aim of this study was to identify predictors of tumor sensitivity to preoperative radiotherapy/chemotherapy for OSCC in order to allow oncologists to determine optimum therapeutic strategies without the associated adverse effects. Here, the protein expression profiles of formalin-fixed paraffin-embedded (FFPE) tissue samples from 18 OSCC patients, termed learning cases, who received preoperative chemotherapy and/or radiotherapy followed by surgery were analyzed by quantitative proteomics and validated by immunohistochemistry in 68 test cases as well as in the 18 learning cases. We identified galectin-7 as a potential predictive marker of chemotherapy and/or radiotherapy resistance, and the sensitivity and specificity of the galectin-7 prediction score (G7PS) in predicting this resistance was of 96.0% and 39.5%, respectively, in the 68 test cases. The cumulative 5-year disease-specific survival rate was 75.2% in patients with resistant prediction using G7PS and 100% in patients with sensitive prediction. In vitro overexpression of galectin-7 significantly decreased cell viability in OSCC cell line. Therefore, our findings suggest that galectin-7 is a potential predictive marker of chemotherapy and/or radiotherapy resistance in patients with OSCC.

Effects of platelet-poor plasma, platelet-rich plasma, and platelet-rich fibrin on healing of extraction sockets with buccal dehiscence in dogs.

Alveolar bone resorption generally occurs during healing after tooth extraction. This study aimed to evaluate the effects of platelet-poor plasma (PPP), platelet-rich plasma (PRP), and platelet-rich fibrin (PRF) on healing in a ridge-augmentation model of the canine socket with dehiscence of the buccal wall. The third mandibular premolars of 12 beagle dogs were extracted and a 3 mm buccal dehiscence from the alveolar crest to the buccal wall of the extraction socket was created. These sockets were then divided into four groups on the basis of the material used to fill the sockets: PPP, PRP, PRF, and control (no graft material) groups. Results were evaluated at 4 and 8 weeks after surgery. The ultrastructural morphology and constructs of each blood product were studied by a scanning electron microscope (SEM) or calculating concentrations of platelets, fibrinogen, platelet-derived growth factor, and transforming growth factor-ß. A total of five microcomputed tomography images of specimens were selected for measurement, and the area occupied by the newly formed bone as well as the horizontal bone width were measured. Moreover, decalcified tissue specimens from each defect were analyzed histologically. The median area of new bone at 4 and 8 weeks and median horizontal bone width at 8 weeks were the highest in the PPP group. However, bone maturation in the PRF and the PRP groups was more progressed than that in the PPP and control groups. By SEM findings, the PRF group showed a more highly condensed fibrin fiber network that was regularly arranged when compared with the PPP and PRP groups. The growth factors released from platelets in PRP indicated higher concentrations than that in PRF. Under more severe conditions for bone formation, as in this experiment, the growth factors released from platelets had a negative effect on bone formation. This study showed that PPP is an effective material for the preservation of sockets with buccal dehiscence.

The impact of miRNA-based molecular diagnostics and treatment of NRF2-stabilized tumors.

UNLABELLED: NF-E2-related factor 2 (NRF2) is a master transcriptional regulator that integrates cellular stress responses and is negatively regulated by Kelch-like ECH-associated protein 1 (KEAP1) at the posttranslational level. In human cancers, aberrantly stabilized NRF2, either by mutation of NRF2 or KEAP1, plays a vital role in chemoresistance and tumor cell growth through the transcriptional activation of target genes, suggesting that targeted inhibition of NRF2 is a potential therapy for NRF2-stabilized tumors. MicroRNAs (miRNA) are endogenous small noncoding RNAs that can negatively regulate gene expression by interfering with the translation or stability of target transcripts. Moreover, tumor-suppressor miRNAs have been suggested to be useful for cancer treatment. Here, a reporter-coupled miRNA library screen identified four miRNAs (miR-507, -634, -450a, and -129-5p) that negatively regulate the NRF2-mediated oncogenic pathway by directly targeting NRF2. Importantly, downregulation of these miRNAs, in addition to the somatic mutation of NRF2 or KEAP1, is associated with stabilized NRF2 and poor prognosis in esophageal squamous cell carcinoma (ESCC). Furthermore, administration of a miR-507 alone or in combination with cisplatin inhibited tumor growth in vivo. Thus, these findings reveal that miRNA-based therapy is effective against NRF2-stabilized ESCC tumors. IMPLICATIONS: This study determines the potential of miRNA-based molecular diagnostics and therapeutics in NRF2-stablized tumors.