A MAP1B-cortactin-Tks5 axis regulates TNBC invasion and tumorigenesis.

The microtubule-associated protein MAP1B has been implicated in axonal growth and brain development. We found that MAP1B is highly expressed in the most aggressive and deadliest breast cancer subtype, triple-negative breast cancer (TNBC), but not in other subtypes. Expression of MAP1B was found to be highly correlated with poor prognosis. Depletion of MAP1B in TNBC cells impairs cell migration and invasion concomitant with a defect in tumorigenesis. We found that MAP1B interacts with key components for invadopodia formation, cortactin, and Tks5, the latter of which is a PtdIns(3,4)P2-binding and scaffold protein that localizes to invadopodia. We also found that Tks5 associates with microtubules and supports the association between MAP1B and α-tubulin. In accordance with their interaction, depletion of MAP1B leads to Tks5 destabilization, leading to its degradation via the autophagic pathway. Collectively, these findings suggest that MAP1B is a convergence point of the cytoskeleton to promote malignancy in TNBC and thereby a potential diagnostic and therapeutic target for TNBC.

Analgesia-based Sedation for Oral Surgery in Patients With Chronic Respiratory Obstructive Disease.

Chronic obstructive pulmonary disease (COPD) is a risk factor for postoperative cardiovascular and respiratory complications. Thus, intravenous sedation can be a better option than general anesthesia for surgery in patients with severe COPD. Herein, we present 2 cases of analgesia-based sedation in patients with severe COPD who underwent oral surgery. The current study aimed to discuss these cases to provide knowledge about the appropriate sedation management in patients with this disease. In the current cases, the patients received sufficient analgesia and minimum sedation (analgesia-based sedation). Moreover, dexmedetomidine was used for maintaining sedation and fentanyl for analgesic effects. Furthermore, we focused on providing the maximum analgesic effect of local anesthesia. The patients' vital signs were stable. They did not have any psychological or physical complaints, such as anxiety and pain, during the procedure. Then, they were discharged from the hospital without any complications. Thus, analgesia-based sedation can be an alternative option for oral surgery in patients with COPD.

Two Cases of Temporomandibular Synovial Chondromatosis Associated with Gli1 Gene Mutation.

Synovial chondromatosis (SC) is a rare benign disease involving multifocal generation of ectopic cartilage in the synovial tissue. Herein, we report two cases of SC in the temporomandibular joint: a 38-year-old woman (patient 1) and 39-year-old woman (patient 2). Both patients had trismus, jaw joint noises, and jaw-opening pain in the temporomandibular joint. Cone-beam computed tomography (CT) and magnetic resonance imaging (MRI) in patient 1 showed multiple calcified loose bodies around the right mandibular condyle. In addition, CT and MRI in patient 2 showed multiple calcified loose bodies around the left mandibular condyle and temporal bone perforation. Following establishing a diagnosis of SC, both patients underwent tumor resection via open surgery. In immunohistochemical examinations of the resected tissues, tumor cells showed intense nuclear staining with labeled anti-Gli1 antibody. Gene sequencing revealed that both patients had a homozygous mutation in the Gli1 gene (rs2228226 G>C). In conclusion, we suggest that the Gli1 gene (rs2228226 G>C) may be involved in the etiology of SC.

Identification of a Cowden syndrome patient with a novel PTEN mutation and establishment of patient-derived induced pluripotent stem cells.

Cowden syndrome (CS) is an autosomal dominant inherited disorder characterized by multiple hamartomas in various organs such as the mucosa, skin, and gastrointestinal tract. Patients with CS are at high risk for breast and thyroid cancers. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene that negatively regulates the AKT pathway, and PTEN mutations are known to be the major causes of this syndrome. However, the pathogenesis of this syndrome has not been clarified. Here, we present a case of a Japanese woman with multiple oral polyps, breast cancer, and thyroid cancer who was clinically diagnosed with CS. We obtained DNA and RNA samples from the patient's peripheral blood mononuclear cells (PBMCs) and buccal mucosa tumor. Next-generation sequencing revealed novel germline mutations (c.1020delT and c.1026G > A) in exon 8 of PTEN. Sanger sequencing identified no PTEN transcript from the mutant allele. Furthermore, CS-specific induced pluripotent stem cells (CS-iPSCs) were established from PBMCs of the patient under feeder- and serum-free culture. Compared with healthy PBMCs and iPSCs, both of the CS-derived PBMCs and CS-iPSCs exhibited significantly reduced expression of the PTEN transcript. The transcriptional variant, PTENδ, was increased in CS-iPSCs, suggesting that it may be the cause of the disease.

Identification of a familial cleidocranial dysplasia with a novel RUNX2 mutation and establishment of patient-derived induced pluripotent stem cells.

Cleidocranial dysplasia (CCD) is an autosomal dominant hereditary disease associated with the gene RUNX2. Disease-specific induced pluripotent stem cells (iPSCs) have emerged as a useful resource to further study human hereditary diseases such as CCD. In this study, we identified a novel CCD-specific RUNX2 mutation and established iPSCs with this mutation. Biopsies were obtained from familial CCD patients and mutation analyses were performed through Sanger sequencing and next generation sequencing. CCD-specific human iPSCs (CCD-hiPSCs) were established and maintained under completely defined serum, feeder, and integration-free condition using a non-integrating replication-defective Sendai virus vector. We identified the novel mutation RUNX2_c.371C>G and successfully established CCD-hiPSCs. The CCD-hiPSCs inherited the same mutation, possessed pluripotency, and showed the ability to differentiate the three germ layers. We concluded that RUNX2_c.371C>G was likely pathogenic because our results, derived from next generation sequencing, are supported by actual clinical evidence, familial tracing, and genetic data. Thus, we concluded that hiPSCs with a novel CCD-specific RUNX2 mutation are viable as a resource for future studies on CCD.

Development of Kikuchi-Fujimoto disease after a cervical lymph node metastasis of mucoepidermoid carcinoma: a case report.

Kikuchi-Fujimoto disease (KFD) was first reported by Kikuchi and Fujimoto in 1972 as a rare disease with lymphadenitis of unknown etiology. KFD is characterized by the main symptoms of fever and enlarged cervical lymph nodes (LNs), which are similar to the features of other LN-associated diseases. Therefore, it is difficult to diagnose this condition. We report the case of a 24-year-old woman who presented with KFD after surgery to treat a mucoepidermoid carcinoma of the palate and dissection of the left neck. The patient presented with a fever and right cervical lymphadenopathy when she visited our department for a regular follow-up related to the mucoepidermoid carcinoma. The results of computed tomography and ultrasonography evaluations led to a clinical diagnosis of lymph node metastasis, and a right neck dissection was performed. However, the pathological tissue analysis did not suggest malignancy but showed necrosis and various cellular infiltrates. We made a diagnosis of KFD from these clinical and pathological features. KFD may be misdiagnosed as a LN-associated disease such as metastasis. Clinically, KFD should be considered in patients with head and neck cancer who present with cervical lymphadenopathy.

Abnormal positioning of the common carotid artery clinically diagnosed as a submandibular mass.

The common carotid artery (CCA) usually runs along the long axis of the neck, although it is occasionally found in an abnormal position or is displaced. We report a case of an 86-year-old woman in whom the CCA was identified in the submandibular area. The patient visited our clinic and reported soft tissue swelling in the right submandibular area. It resembled a tumor mass or a swollen lymph node. Computed tomography showed that it was the right CCA that had been bent forward and was running along the submandibular subcutaneous area. Ultrasonography verified the diagnosis. No other lesions were found on the diagnostic images. Consequently, the patient was diagnosed as having abnormal CCA positioning. Although this condition generally requires no treatment, it is important to follow-up the abnormality with diagnostic imaging because of the risk of cerebrovascular disorders.

Suture granulomas developing after the treatment of oral squamous cell carcinoma.

INTRODUCTION: Suture granuloma is a benign tumor that develops because of the presence of surgical suture materials. It commonly occurs several years after different types of surgeries. Here we report a case involving a 64-year-old man who underwent head and neck surgery for oral squamous cell carcinoma and developed multiple suture granulomas mimicking tumor recurrence in the radiation field just a few days after the completion of adjuvant chemoradiation therapy. PRESENTATION OF CASE: The patient underwent surgery for lymph node metastasis in the neck at 6 months after the resection of primary oral squamous cell carcinoma. Fifteen days after the completion of adjuvant chemoradiation therapy at a total dose of 50 Gy, small nodules appeared in the radiation field, along the areas of the subcutaneous surgical sutures. Cancer recurrence was initially suspected, but histopathological analysis of a biopsy specimen confirmed foreign body granuloma. DISCUSSION: Chemoradiation therapy may enhance the immunoreaction of macrophages in the radiation field and promote the formation of granulation tissue in a short period of time. In addition, cisplatin, which was concurrently administered with radiation in our case, could have influenced the development of the suture granuloma. CONCLUSION: In addition to tumor recurrence, suture granulomas should be considered a differential diagnosis for nodules occurring after surgery, even if they develop in the field of radiation.

Photodynamic therapy using Photofrin and excimer dye laser treatment for superficial oral squamous cell carcinomas with long-term follow up.

OBJECTIVES: Photodynamic therapy (PDT) is a very effective treatment for superficial malignancies that does not result in loss of normal tissue. Here, we report successful PDT treatment of superficial oral cancers and its clinical outcome with long-term follow up. MATERIALS AND METHODS: Thirty-four superficial oral squamous cell carcinomas were treated with PDT, and the effects were evaluated. Each patient received Photofrin (2mg/kg) intravenously 48h prior to light irradiation. Photoradiation was performed at doses of 100-150J/cm(2) using a 630-nm wavelength excimer dye laser. RESULTS: Six months after PDT, 30 patients (88.2%) showed complete responses while 9 patients (26.5%) had local relapses during long-term follow-up. The 5-year overall survival, disease-specific survival, and disease-free survival rates were 76.5%, 84.6%, and 63.3%, respectively. Lesions with red patches had a significantly higher recurrence rate than lesions with white patches. Accurate evaluation of the extent of lesions and appropriate photoradiation were important in improving outcomes. Adverse events observed included sunburn and sequestrum formation of alveolar bone. No abnormal laboratory values or systemic complications were observed. CONCLUSION: PDT using Photofrin as the photosensitizer is an effective treatment modality for superficial oral carcinomas, with excellent healing and minimal side effects.