Malignant phosphaturic mesenchymal tumor, mixed connective tissue variant of the tongue

金沢大学医薬保健研究域医学系The majority of the oncogenic osteomalacia-associated mesenchymal tumors are considered to belong to the category of phosphaturic mesenchymal tumors, mixed connective tissue (PMTMCT) variant, of which malignant cases are very rare. Here we report a case of a recurrent malignant PMTMCT variant which arose in the tongue. The patient was treated with surgery at an initial treatment and the first recurrence. In accordance with the tumor recurrence and resection, the hypophosphatemia progressed and improved. However, hypophosphatemia did not progress after receiving radiation therapy at the second recurrence even though the recurrent tumor gradually increased its size. These results suggest clinical feature of malignant PMTMCT could be changed by radiation therapy. Thus, this report could add an insight to the nature of PMTMCT. © 2008 Elsevier Ireland Ltd. All rights reserved

Cricoid ossification mimicking an impacted foreign body.

金沢大学医学部附属病院耳鼻咽喉科A 54-year-old man complained of severe throat pain and showed subglottic oedema on fibre-optic endoscopy with a distinctly narrowed subglottic space on anteroposterior radiography of the neck and dense linear opacity at the level of the cricoid cartilage on lateral plain radiography. These findings suggested a foreign body just posterior to the cricopharyngeus, but a computed tomography (CT) scan demonstrated a dense calcified ridge on the posterior lamina of the cricoid cartilage but no foreign body.The patient improved symptomatically with systemic antibiotics and topical steroids, and gastrointestinal endoscopy did not detect any foreign body. This is a rare case of vertical ossification of the cricoid lamina masquerading as a foreign body

A case report: Epstein-Barr virus-associated undifferentiated carcinoma of the tongue base

金沢大学大学院医学系研究科脳病態医学Outside the nasopharynx, undifferentiated carcinomas occur only rarely at other head and neck locations. Although the association between undifferentiated nasopharyngeal carcinoma and Epstein-Barr virus (EBV) is consistent, there is conflicting evidence as to the association of EBV with undifferentiated carcinomas outside the nasopharynx. Here, we report on a case of undifferentiated carcinoma of the tongue base. A 71-year-old male, who had been treated with irradiation for primary unknown right neck metastatic EBV-positive undifferentiated carcinoma 9 years previously, was referred to our clinic with masses at the tongue base and right neck. The lesion at the tongue base was revealed to be an EBV-positive undifferentiated carcinoma. He was treated with resection of tongue base tumor and bilateral-neck dissection, and the defect at the tongue base was reconstructed with a free rectus abdominis myocutaneous flap. Re-irradiation was added post-operatively because of a positive surgical margin at the tongue base. The patient is presently alive without recurrence or distant metastasis 20 months after treatment. Although it is unclear whether our case is recurrent or newly developed EBV-latently infected undifferentiated carcinoma, we propose that EBV-associated tumors should be carefully observed after treatment at least for more than 10 years. © 2006 Elsevier Ireland Ltd. All rights reserved

Post-operative pharyngocutaneous fistula after laryngectomy

金沢大学附属病院耳鼻咽喉科Objectives: Although organ-preserving radiotherapy or chemoradiotherapy has offered good locoregional control, many patients still experience recurrent disease requiring salvage laryngectomy. The pharyngocutaneous fistula (PCF) is a common and troublesome complication in the early post-operative period after laryngectomy. Here, we evaluated the cause of PCF after laryngectomy, with special emphasis on radiotherapy and/or chemotherapy. Patients and methods: A total of 63 consecutive patients undergoing salvage total laryngectomy for squamous cell carcinoma of the larynx at Kanazawa University Hospital from 1990 to 2005 were reviewed. Forty of the 63 had received primary total laryngectomy (PL). Ten patients underwent radiotherapy alone (SL-RT) and 13 patients underwent concurrent chemoradiotherapy (SL-CRT) followed by salvage laryngectomy. Results: Overall, 17 of the 63 patients (27.0%) developed PCF after laryngectomy. Fisher\u27s exact test showed a significant increase of PCF formation in SL-CRT (7/13, 53.8%) compared with PL (7/40, 17.5%) (p = 0.0252). There were non-significant increases of PCF formation both in SL-CRT (7/13, 53.8%) compared with SL-RT (3/10, 30.0%) (p = 0.4015), and also in SL-RT (3/10, 30.0%) compared with PL (7/40, 17.5%) (p = 0.3969). The Mann-Whitney U-test showed that the duration of PCF was significantly longer for SL-CRT PCF (121.2 ± 95.0 days) compared with those for PL (39.0 ± 55.3 days) (p = 0.0298) or SL-RT (28.0 ± 16.2 days) (p = 0.0325). However, we did not find a significant difference in the duration of PCF with respect to PL (39.0 ± 55.3 days) and SL-RT (28.0 ± 16.2 days) (p = 0.4367). Conclusions: Although radiotherapy or chemotherapy has only a limited impact on PCF formation, concurrent chemoradiotherapy significantly increases PCF formation. The addition of chemotherapy to irradiation delays PCF closure. © 2007 Elsevier Ireland Ltd. All rights reserved

Induction of receptor for advanced glycation end products by EBV latent membrane protein 1 and its correlation with angiogenesis and cervical lymph node metastasis in nasopharyngeal carcinoma.

金沢大学医薬保健研究域医学系PURPOSE: The EBV oncoprotein, latent membrane protein 1 (LMP1), contributes to the metastasis of nasopharyngeal carcinoma (NPC) by inducing factors to promote tumor invasion and angiogenesis. The receptor for advanced glycation end products (RAGE) is associated with abnormal angiogenesis in diabetic microangiopathies. Moreover, some papers have suggested the association of RAGE overexpression with tumor metastasis; thus, the associations of RAGE with LMP1 and angiogenesis in NPC were examined. EXPERIMENTAL DESIGN: Forty-two patients with NPC were evaluated for expressions of LMP1, RAGE, and S100 proteins and for microvessel counts by immunohistochemistry. Then, the RAGE induction by LMP1 was examined with Western blotting and luciferase reporter assay. RESULTS: The microvessel counts were significantly higher in patients with high LMP1 expression or high RAGE expression compared with cases with low expressions (P=0.0049 and P<0.0001), respectively. Patients with advanced N classification were also significantly increased in these groups (P=0.0484 and P=0.0005). The expressions of LMP1 and RAGE proteins were clearly correlated in NPC tissues (P=0.0093). Transient transfection with LMP1 expression plasmid induced RAGE protein in Ad-AH cells. The expression of LMP1 transactivated the RAGE promoter as shown by luciferase reporter assay. Mutation of the reporter at nuclear factor-kappaB binding site (-671 to -663) abolished transactivation of the RAGE promoter by LMP1. CONCLUSION: These results suggest that LMP1-induced RAGE enhances lymph node metastasis through the induction of angiogenesis in NPC. Nuclear factor-kappaB binding site (-671 to -663) is essential for transactivation of the RAGE promoter by LMP1.全文公開20090

Case of three delayed complications of radiotherapy: Bilateral vocal cord immobility, esophageal obstruction and ruptured pseudoaneurysm of carotid artery

金沢大学医薬保健研究域医学系We report the first case of three delayed complications following irradiation for laryngeal carcinoma: bilateral vocal cord immobility, obstruction of esophagus and spontaneously ruptured pseudoaneurysm of common carotid artery. Medial fixation of bilateral vocal cords and stenosis of cervical esophagus were noted at 28 years after radiotherapy. Spontaneous rupture of a pseudoaneurysm bulging into the hypopharynx and obstruction of the esophagus occurred at 35 years after irradiation. The life-threatening hemorrhage was successfully treated by microcoil embolization of the common carotid artery. The relationship between these complications and irradiation is also discussed. © 2008 Elsevier Ireland Ltd. All rights reserved

Cleavage of Amyloid-β Precursor Protein (APP) by Membrane-Type Matrix Metalloproteinases

Division of Molecular Viology and Oncolog

Cleavage of amyloid-β precursor protein (APP) by membrane-type matrix metalloproteinases

金沢大学がん研究所がん病態制御Amyloid-β precursor protein (APP) was identified on expression cloning from a human placenta cDNA library as a gene product that modulates the activity of membrane-type matrix metalloproteinase-1 (MT1-MMP). Co-expression of MT1-MMP with APP in HEK293T cells induced cleavage and shedding of the APP ectodomain when co-expressed with APP adaptor protein Fe65. Among the MT-MMPs tested, MT3-MMP and MT5-MMP also caused efficient APP shedding. The recombinant APP protein was cleaved by MT3-MMP in vitro at the A463-M 464, N579-M580, H622-S 623, and H685-Q686 peptide bonds, which included a cleavage site within the amyloid β peptide region known to produce a C-terminal fragment. The Swedish-type mutant of APP, which produces a high level of amyloid β peptide, was more effectively cleaved by MT3-MMP than wild-type APP in both the presence and absence of Fe65; however, amyloid β peptide production was not affected by MT3-MMP expression. Expression of MT3-MMP enhanced Fe65-dependent transactivation by APP fused to the Gal4 DNA-binding and transactivation domains. These results suggest that MT1-MMP, MT3-MMP and MT5-MMP should play an important role in the regulation of APP functions in tissues including the central nervous system. © 2006 The Japanese Biochemical Society

A solitary fibrous tumor arising in the parapharyngeal space, with MRI and FDG-PET findings

金沢大学医薬保健研究域医学系We present the imaging and pathological features of a 38-year-old man in whom a large parapharyngeal solitary fibrous tumor (SFT) on the left side was found. On MRI, the tumor showed a nodule-in-nodule appearance. The inner nodule revealed high signal intensities both on T1- and T2-weighted MR images. The entire tumor showed heterogeneous enhancement on gadolinium-enhanced T1-weighted images. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) identified heterogeneous radiotracer uptake of FDG in the inner nodule of the tumor. Histologic examinations revealed an admixture of growth patterns, including a "patternless pattern" and "haemangiopericytoma-like pattern". The tumor was positive for CD34. Imaging features of SFT arising in the parapharyngeal space are discussed with a review of literatures. This is the first report of FDG-PET finding of SFT arising in the head and neck. More cases are needed to achieve diagnostic significance from FDG-PET findings of parapharyngeal SFTs. © 2008 Elsevier Ireland Ltd. All rights reserved

Impact of MDM2 single nucleotide polymorphism on tumor onset in head and neck squamous cell carcinoma

金沢大学附属病院耳鼻咽喉科・頭頸部外科Conclusions. The GG genotype of MDM2 SNP309 is associated with an earlier onset of head and neck squamous cell carcinoma (HNSCC) in the Japanese population. SNP309 may be a key factor in the tumorigenesis of HNSCC as well as other hereditary or sporadic tumors. Objective. This study was designed to evaluate the association between the single nucleotide polymorphism (SNP) 309 in the MDM2 gene with HNSCC. An MDM2 protein down-regulates the p53 pathway. Recently, an important SNP was discovered in the MDM2 promoter region, which could affect the tumorigenesis of HNSCC by attenuation of the p53 pathway. Patients and methods. Patients with 103 HNSCCs were genotyped using direct sequencing and real-time PCR. The relationship between the SNP309 genotypes and the clinicopathological features was statistically analyzed. Results. The number of patients genotyped to TT, TG, and GG was 29 (28%), 46 (44.7%), and 28 (27.2%), respectively. The average age at tumor onset was 65.6 years for TT, 62.9 years for TG, and 56.7 years for GG. The patients with the GG genotype had a significantly earlier tumor onset in comparison to those with the TT genotype (p=0.032). © 2008 Taylor & Francis.全文公開20090