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Recently, targeted drugs have been developed for the treatment of colorectal cancer(CRC). Among targets, it is well known that KRAS mutations are associated with resistance to epidermal growth factor receptor(EGFR)monoclonal antibodies. However, response rates using anti-EGFR monotherapy for CRC were less than 20-30% in previous clinical studies. Thus, because the RAS/MAP2K/MAPK and PI3K/AKT pathways are associated with CRC resistance to chemotherapy, we analyzed gene mutations in Stage IV CRC patients using a genomic test(CancerPlex®). Medical records were reviewed for 112 patients who received treatment for CRC between 2007 and 2015 in Niigata University Medical and Dental Hospital or Niigata Cancer Center Hospital. There were 66 male and 46 female patients, and their median age was 62.5(range, 30-86) years. Cluster analyses were performed in 110 non-hypermutated Japanese CRC patients using Euclidean distance and Ward's clustering method, and 6 typical groups were identified. Among these, patients with all wild-type actionable genes benefited from anti-EGFR therapies. The expense of targeted drugs warrants consideration of cost-effectiveness during treatment decision-making for advanced CRC patients. To this end, based on the genetic information on CRC, it is possible to develop precision medicine using CancerPlex®.

SUMMARY An equivalent circuit model for a semiparallel plate electrostatic torsion mirror has been developed based on an electrical circuit simulator. An analytical model for the electrostatic torque has been translated into a nonlinear dependent current source as a function of the input voltages that interpret the drive voltages and the mirror angle. Use of the suspension width as a fitting parameter explained well the experimental results on frequency response and the mirror's static deflection. © 2013 Wiley Periodicals, Inc. Electron Comm Jpn, 97(1): 37–47, 2014; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.11486

It is known that tumour necrosis factor (TNF)-α converting enzyme (TACE) plays a crucial role in fibrotic inflammatory diseases, and is specifically inhibited by tissue inhibitor of metalloproteinase (TIMP)-3. Fibrotic drug-induced gingival overgrowth (GO) is often combined with periodontitis. However, neither TACE nor TIMP-3 has been thoroughly examined in periodontal tissues to date. The aim of the present study was to analyse mRNA expression of TACE and TIMP-3, and protein localisation of TACE in gingival tissues removed from drug-(calcium-channel blocker) induced GO and periodontitis.A total of 30 gingival tissue samples were taken from 15 GO and 15 periodontitis patients. The mRNA expression levels were analysed by quantitative reverse transcription polymerase chain-reaction (qRT-PCR) and the protein localisation was investigated by immunohistochemistry. Statistical analysis was performed using the Mann-Whitney U-test.TACE and TIMP-3 mRNA levels were significantly higher in GO compared to the periodontitis groups, as revealed by qRT-PCR (p0.05). TACE-producing cells were immunohistochemically detected among monocytes/macrophages, plasma cells and some epithelial cells. TACE immunoreactivity was shown to be more intense in GO than in periodontitis-gingival tissue.We have demonstrated TACE expression in cells such as macrophages, plasma cells and epithelial cells, and its predominant expression in GO tissues. This data suggests that TACE expression in GO-gingiva could be involved in the pathogenesis of disease.

There is a need for accurate dosimetry for studies of health effects in the Japanese atomic bomb survivors because of the important role that these studies play in worldwide radiation protection standards. International experts have developed dosimetry systems, such as the Dosimetry System 2002 (DS02), which assess the initial radiation exposure to gamma rays and neutrons but only briefly consider the possibility of some minimal contribution to the total body dose by residual radiation exposure. In recognition of the need for an up-to-date review of the topic of residual radiation exposure in Hiroshima and Nagasaki, recently reported studies were reviewed at a technical session at the 57th Annual Meeting of the Health Physics Society in Sacramento, California, 22-26 July 2012. A one-day workshop was also held to provide time for detailed discussion of these newer studies and to evaluate their potential use in clarifying the residual radiation exposures to the atomic-bomb survivors at Hiroshima and Nagasaki. Suggestions for possible future studies are also included in this workshop report.

A case of solitary central neurofibroma of the mandible arising in a 70-year-old man is reported. The patient had a radiolucent lesion, measuring 16 mm in diameter, with central radiopaque freckles in the right incisor–canine region of the mandible, which was discovered incidentally during routine dental check-up. The lesion was persisted for 10 years without any symptoms or complication. It was clinically diagnosed as benign tumor and surgically removed under general anesthesia. Histologically, the removed tumor was relatively well demarcated and composed of a sparse proliferation of elongated spindle-shaped cells with wavy nuclei in loosely textured connective tissue stroma, which was associated with bone formation. Clinicopathological features of central neurofibroma of the jaw bone are reviewed from the literature. This is the first report of central neurofibroma arising in the anterior part of the mandible.

Although the histopathogenetic process of keratin pearls is still poorly understood, acceleration of keratinization in squamous cell carcinoma (SCC) cells may represent one possible therapeutic avenue. Based on our histopathological observations, we have hypothesized that SCC cells are keratinized by phagocytosis of extravasated erythrocytes. To confirm this hypothesis, we firstly examined immature keratin pearls in oral carcinoma in situ (CIS) and mature ones in SCC by immunohistochemistry. Concentric dyskeratotic cells in CIS keratin pearls became positive for keratin (K) 10, K17, heme oxygenase-1 (HO-1), or protease activated receptor-2 (PAR-2), a candidate regulator for hemophagocytosis. When ZK-1 cells, an SCC cell system, were incubated with human peripheral blood erythrocytes, or with crude and purified hemoglobins (Hbs), their erythro-hemophagocytotic activities were confirmed by immunofluorescence. Immunofluorescence signals for K10, K17, and HO-1 were enhanced due to hemophagocytosis in time-dependent manners. mRNA expression levels for the three molecules were most enhanced by purified Hb, followed by crude Hb and erythrocytes. K17/K10 mRNA expression levels were more elevated when PAR-2 was activated in ZK-1 cells. The results indicated that immature and mature keratin pearls in CIS and SCC were generated by oxidative stresses derived from erythro-hemophagocytosis, which might mediate HO-1 expression and be regulated by PAR-2. Thus, hemorrhage from the rupture of blood vessels can be one of the triggers for keratin pearl formation in oral CIS and SCC. J. Cell. Physiol. 228: 1977–1988, 2013. © 2013 Wiley Periodicals, Inc.

Accepted: 2013-01-15, 資料番号: SA1004637000

Aim: The aim of this retrospective study was to show the efficacy and safety of modified FOLFOX6 plus high-dose bevacizumab (10 mg/kg/2 weeks) in the second-line or later treatment of metastatic colorectal cancer. Methods: A total of 24 consecutive patients treated between August 2007 and August 2009 were included in this retrospective study. None of the patients had received bevacizumab as part of prior treatment. Results: All 24 patients received modified FOLFOX6 plus high-dose bevacizumab and were followed for a median of 36.9 months. Overall response rate was 29%. Median progression-free survival was 7.5 months, and median overall survival was 17.3 months. Grade 3/4 adverse events were: neutropenia (54.2%), leukopenia (25.0%), neuropathy (12.5%), hypertension (12.5%), thrombocytopenia (8.3%), and decreased haemoglobin, gastrointestinal haemorrhage, wound complications, nausea, diarrhoea, mucositis and fatigue (each 4.2%). Conclusion: Modified FOLFOX6 plus high-dose bevacizumab may be useful in the second-line treatment of patients with metastatic colorectal cancer who have not received bevacizumab.

Background: This study attempted to determine the therapeutic dosage of irinotecan and S-1 (IRIS) as a second-line treatment for colorectal cancer (CRC). Methods: S-1 was administered on days 1-14 of a 28-day cycle. Irinotecan was administered on days 1 and 15. The irinotecan dose was then escalated to determine the maximum-tolerated dose and the recommended dose at a fixed dosage of S-1 (80 or 65 mg·m-2·day-1). The S-1 dose was reduced to 65 mg·m-2·day-1 when dose-limiting toxicities were observed at 80 mg·m-2· day-1 and the irinotecan dose was increased. Results: The recommended dose was 65 mg/m2 for S-1 and 75 mg/m2 for irinotecan. Twenty-one patients were treated at the recommended dose. The overall response rate was 28.6%. Conclusion: This modified IRIS regimen is considered effective with acceptable toxicities for advanced CRC resistant to treatment with 5-fluorouracil/leucovorin or uracil and tegafur/leucovorin.

Although “teeth clenching” induces pressor response, the reflex tracts of the response are unknown. In this study, dantrolene administration inhibited teeth clenching generated by electrical stimulation of the masseter muscles and completely abolished the pressor response. In addition, trigeminal ganglion block or hexamethonium administration completely abolished the pressor response. Local anesthesia of molar regions significantly reduced the pressor response to 27 ± 10%. Gadolinium (mechanoreceptor blocker of group III muscle afferents) entrapment in masticatory muscles also significantly reduced the pressor response to 62 ± 7%. Although atropine methyl nitrate administration did not change the pressor response, a significant dose-dependent augmentation of heart rate was observed. These results indicate that both periodontal membrane and mechanoreceptors in masticatory muscles are the receptors for the pressor response, and that the afferent and efferent pathways of the pressor response pass through the trigeminal afferent nerves and sympathetic nerves, respectively.

Primary gastrointestinal follicular lymphoma (FL) has an indolent clinical presentation and many of cases are diagnosed incidentally during routine endoscopic examinations. Herein, we present 3 cases with FL of the small intestine developed massive intestinal hemorrhage that necessitated blood transfusion. In all three patients, upper and lower endoscopic examinations failed to detect the bleeding sites. Eventually, video capsule endoscopies identified ulcerative lesions in the jejunum and biopsies using single- or double-balloon endoscopy confirmed the FL diagnosis in our three cases. The respective clinical stages according to the Lugano system were I, II-1 and II-1. PET-CT did not play a significant role in identifying the gastrointestinal lesions. Two patients received rituximab monotherapy and achieved a complete response. The other remains under observation after termination of antiplatelet drug therapy. Generally, the macroscopic appearance of multiple whitish nodules and the absence of symptoms represent the typical clinical picture of gastrointestinal FL. However, this study demonstrates that patients with ulcerative lesions may be at risk for massive bleeding. Further discussion is required to determine the optimal indications for total endoscopic examination of the small intestine.

Among various electron-beam lithography (EBL) techniques, variable-shaped beam (VSB) and character projection (CP) methods have attracted many EBL users for their high-throughput feature, but they are considered to be more suited to small-featured VLSI fabrication with regularly-arranged layouts like standard-cell logics and memory arrays. On the other hand, non-VLSI applications like photonics, MEMS, MOEMS, and so on, have not been fully utilized the benefit of CP method due to their wide variety of layout patterns. In addition, the stepwise edge shapes by VSB method often causes intolerable edge roughness to degrade device characteristics from its intended performance with smooth edges. We proposed an overall EBL methodology applicable to wade-variety of EBL applications utilizing VSB and CP methods. Its key idea is in our layout data conversion algorithm that decomposes curved or oblique edges of arbitrary layout patterns into CP shots. We expect significant reduction in EB shot count with a CP-bordered exposure data compared to the corresponding VSB-alone conversion result. Several CP conversion parameters are used to optimize EB exposure throughput, edge quality, and resultant device characteristics. We demonstrated out methodology using the leading-edge VSB/CP EBL tool, ADVANTEST F7000S-VD02, with high resolution Hydrogen Silsesquioxane (HSQ) resist. Through our experiments of curved and oblique edge lithography under various data conversion conditions, we learned correspondence of the conversion parameters to the resultant edge roughness and other conditions. They will be utilized as the fundamental data for further enhancement of our EBL strategy for optimized EB exposure.

Case 1: A 61-year-old man who had a diagnosis of low rectal cancer with lateral pelvic lymph node (LPLN) metastasis and multiple liver metastases underwent low anterior resection with LPLN dissection. The initial surgery was followed by chemotherapy, and then an extended right hepatectomy with partial resection of the liver was performed. Subsequently, a lung metastasis was detected, and the lung was partially resected. The patient was alive 9 years and 6 months after the initial operation. Case 2: A 53-year-old man had a diagnosis of low rectal cancer. After 5 courses of mFOLFOX6 plus bevacizumab, he underwent low anterior resection with LPLN dissection and resection of the peritoneal metastasis. The patient was alive 6 years and 3 months after the surgery without any signs of recurrence. Case 3: A 48-year-old man had a diagnosis of low rectal cancer and multiple liver metastases. He underwent low anterior resection with LPLN dissection and right hepatic lobectomy. He subsequently showed liver and lung metastases. The patient received systemic chemotherapy, and is alive with recurrent disease. We report 3 cases of Stage Ⅳ low rectal cancer with LPLN metastasis, and propose that LPLN dissection is important as a part of R0 resection for Stage Ⅳ low rectal cancer.

Objective The aim of this study is to characterize immunohistochemical profiles of lining epithelia of nasopalatine duct cyst (NPC) as well as to correlate those findings with their clinicopathological features to understand the histopathogenesis of NPC. Materials and methods Forty-one surgical specimens from NPC were examined for clinical profiles and expression of keratin-7, 13, MUC-1, and P63 by immunohistochemistry, compared to radicular cyst (RC) and maxillary sinusitis. Results Nasopalatine duct cyst was clinically characterized by male predominant occurrence: 44% of the cases involved tooth roots, and 70% with inflammatory backgrounds. Lining epithelia of NPCs without daughter cysts were immunohistochemically distinguished into three layers: a keratin 7-positive (+) ciliated cell layer in the surface, a keratin-13+ middle layer, and a MUC-1+/P63+ lower half, indicating that they were not respiratory epithelia, and the same layering pattern was observed in RC. However, those immunolocalization patterns of the main cyst lining with daughter cyst were exactly the same as those of daughter cyst linings as well as duct epithelia of mucous glands. Conclusions Two possible histopathogeneses of NPC were clarified: one was inflammatory cyst like RC and the other was salivary duct cyst-like mucocele.

We have developed a new conceptual liquid crystal display (LCD) with a memory circuit and a photosensor in each pixel to realize excellent handwriting performance. Direct writing and erasing a character in the LCD are available because their direct processing only in the pixel are performed without calculating coordinates by using a light pen and integrated pixel circuits. In addition, this LCD enables to display still image data stored in the pixel memory circuit at a low liquid crystal (LC) driving frequency of 1.0 Hz. In the result, we have achieved faster handwriting response time of 0.5 ms and lower power consumption of 0.7 mW in 7.0-in. QVGA reflective LCD panel.

Kobayashi T, Maruyama S, Abe T, Cheng J, Takagi R, Saito C & Saku T (2012) Histopathology 61, 910–920 Keratin 10-positive orthokeratotic dysplasia: a new leucoplakia-type precancerous entity of the oral mucosa Aims: We investigated a group of oral mucosal lesions with characteristic hyperorthokeratotic foci, which we termed orthokeratotic dysplasia (OKD), to determine if it could be identified as a distinct histopathological entity. Methods and results: We screened 282 surgical specimens from 200 patients with oral leucoplakia-type squamous cell carcinoma (SCC) or carcinoma in situ (CIS). OKD was defined as an oral mucosal lesional focus in which hyperorthokeratosis was predominant in the presence of the granular cell layer. A total of 84 OKD foci from 62 cases found among the 200 SCC/CIS cases were analysed. According to its rete ridge shapes, OKD was classified into three subtypes: flat (14.3%), leg (63.1%) and intermediate (22.6%). Eighty per cent of OKD foci were adjacent to the main foci of SCC or CIS, and they were demarcated sharply from each other. Most of the OKD constituent cells were immunopositive for keratin 10, but not for keratins 13, 17 or 19. Numbers of Ki-67-positive cells in the first basal layer were greater in OKD than in normal epithelia. Conclusions: The findings indicate that OKD is a distinct variant of epithelial dysplasia related to malignancies, and hence that it is important to recognize its existence.

The colorimetric in situ hybridization (CISH)-based matrix metalloproteinase (MMP)-to-E-cadherin (ECD) ratio (MER) has been revealed as an excellent marker for the disease stage in prostate cancer. The one aim of this study was investigating a new method for estimation of MER by bicolor fluorescent ISH (bicolor FISH) with a computerized fluorescence detector-based system. Another aim was examination of relation of MER by bicolor FISH with expression of vascular endothelial growth factor-C (VEGF-C).The bicolor FISH technique used cyanin 5 (cy5)-labeled MMP-2 and -9 probes, and a cyanin 3 (cy3)-labeled ECD probe on needle biopsy specimens from 67 prostate cancer cases. The ISH was followed by computerized detection of the signal intensities and cy5-to-cy3 ratios using a fluorescence detector. VEGF-C expression was examined using cy5-labeled VEGF-C by computerized detection.The bicolor FISH-based MER was well correlated with CISH-based MER (P0.0001). The bicolor FISH-based MER correlated with Gleason score and pathologic stage of the cases. VEGF-C mRNA expression was associated with the pathologic stage and maximum lymph vessel density (LVD). The LVD was associated with VEGF-C expression at the tumor area where the maximum MER was detected (P0.0001).The MER was correlated with the VEGF-C expression and LVD, indicating lymph node metastasis of prostate cancer. Therefore, this computer-assisted MER is a useful marker for preoperative prediction of disease stage, especially lymph node metastasis, of prostate cancer.

It can be difficult to make a certain diagnosis in case of an oral borderline malignant lesion on hematoxylin-eosin-stained sections only. Furthermore, assessment of surgical margins of borderline lesions is difficult with the naked eye. We set out to determine the topographical distribution of capillary blood vessels within the epithelial zone and to assess its use as an aid for histopathological diagnosis and a framework for clinical assessment of lesional margins using optical techniques, such as narrow-band imaging (NBI) endoscopy. Capillary blood vessels entrapped in the epithelial compartment, which we have designated as intraepithelially entrapped blood vessels (IEBVs), were examined for their frequency, location, and shape in normal mucosa, dysplasia, and carcinoma in-situ (CIS) of the tongue using immunohistochemistry for CD31 and type IV collagen. When counted per unit length of epithelial surface, IEBVs increased in number significantly in CIS (5.6 ± 2.8), which was two times more than in normal (1.9 ± 1.6) and dysplastic (2.4 ± 1.5) epithelia. In addition, IEBVs in CIS had compressed shapes with occasional obstruction or collapse with hemorrhage and were arranged perpendicular to and extending up to the epithelial surface. These characteristic IEBVs in CIS were considered to be generated by complex expansion of rete ridges due to carcinoma cell proliferation within the limited epithelial space determined by the basement membrane. The recognition of IEBVs was helpful in the differential diagnosis of oral CIS, and the present data provide a valuable frame of reference for detecting oral CIS areas using such NBI-based optical devices.

An equivalent circuit model for the semi-parallel plate electrostatic torsion mirror has been developed based on the electrical circuit simulator. An analytical model for the electrostatic torque has been translated into a nonlinear dependent current source as a function of input voltages that interpret the drive voltages and the mirror angle. A use of the suspension width as a fitting parameter explained well the experimental results of frequency response and the mirror's static deflection.

An equivalent circuit model for the resonant-type vertical comb-driven optical MEMS (micro electro mechanical system) scanner has been developed based on the simple extension of the parallel-plate model. Both the electrostatic torque and the induction charge models are interpreted by using the equation-defined nonlinear dependent current source on the electrical circuit simulator platform. A systematic procedure has been investigated to fit the analytical model with the experimental results by using fitting parameters including the damping coefficient, the suspension width, and the comb gap. The developed simulation model has been used to verify a new control scheme to tune the scanner's oscillation amplitude in resonance by means of the pulse-width modulation of voltage at a given pulse height; the result indicates the effective use of digital electronics for the comb-driven optical scanner.

The current Japanese general rules for clinical and pathologic studies on cancer of the colon, rectum, and anus state that a 3-cm distal resection margin is needed in resecting rectosigmoid cancer and rectal cancer with a distal edge above the peritoneal reflection, and 2 cm is needed for rectal cancer with a distal edge below the peritoneal reflection. The appropriateness of these rules has not been proved.Our aim was to evaluate the appropriateness of the Japanese rules.We retrospectively analyzed surgical and pathology records of patients who underwent surgery at a tertiary care cancer center in Japan.The study included 381 consecutive patients with stage I to IV rectosigmoid or rectal cancer without preoperative chemotherapy or radiotherapy.We investigated both intramural and mesorectal distal spread, using whole-mount sections to measure the maximum length of distal spread. Long distal spread was defined as distal spread longer than the distal resection margin stated in the Japanese general rules. Risk factors for both distal spread and long distal spread were evaluated.Of 381 patients, 325 (85.3%) had no distal spread and a total of 56 (14.7%) had distal spread. Distal spread was within the limits specified by the Japanese general rules in 48 of the 381 patients (12.6%) and beyond the Japanese limits (long distal spread) in 8 patients (2.1%). The prevalence of distal spread increased with TNM stage (stage I, 2.7%; stage II, 5.3%; stage III, 17.4%; stage IV, 46.2%). Long distal spread was not observed in stage I or II, was found in only 1.4% of patients with stage III disease and in 11.5% of patients with stage IV. The maximum extent of distal spread in patients with rectosigmoid cancer or rectal cancer with the distal edge above the peritoneal reflection was 38 mm; in patients with rectal cancer with the distal edge below the peritoneal reflection, 35 mm. Multivariable analyses showed that nodal involvement and distant metastasis were independent risk factors for distal spread; distant metastasis was the only independent risk factor for long distal spread.The Japanese general rules specifying the distal resection margin are appropriate for most patients who undergo surgery for rectosigmoid and rectal cancer without preoperative chemotherapy or radiotherapy. A further increase of 1 to 2 cm beyond the recommended distal resection margin may contribute to improved local control for patients with distant metastasis.

J Oral Pathol Med (2012) 41: 372–378 Objectives: A precancerous condition is a lesion that, if left untreated, leads to cancer or can be induced to become malignant. In the oral region, leukoplakia is a lesion that has been regarded as precancerous. In cases of oral carcinoma, we have frequently noticed that a type of leukoplakia histologically demonstrating hyper-orthokeratosis and mild atypia (ortho-keratotic dysplasia; OKD) is often associated with carcinoma, either synchronously or metachronously. Therefore, we consider OKD-type leukoplakia to be a true precancerous lesion. Materials and Methods: In an attempt to clarify the relationship between OKD as a precancerous condition in the oral mucosa and telomere length, we estimated telomere lengths in this type of leukoplakia using quantitative fluorescence in situ hybridization, and also quantified the frequency of anaphase–telophase bridges (ATBs) in comparison with squamous cell carcinoma in situ (CIS) and the background tissues of CIS and OKD. Results: Ortho-keratotic dysplasia was frequently associated with squamous cell carcinoma (45.0%) and showed significantly shorter telomeres than normal control epithelium, CIS, or the background of CIS or OKD. The frequency of ATBs was much higher in OKD than in control epithelium or CIS. Conclusion: Ortho-keratotic dysplasia appears to be frequently associated with carcinoma, chromosomal instability, and excessively shortened telomeres, not only in the lesion itself but also in the surrounding background. Therefore, when this type of leukoplakia is recognized in the oral region, strict follow-up for oral squamous cell carcinoma is necessary, focusing not only on the areas of leukoplakia, but also the surrounding background.

Introduction Physiological responses to +Gz stress have been reported in several studies. However, no reports exist on differences in arterial pressure responses between increasing and decreasing G phases. We hypothesized that +Gz stress and/or an anti-G support might disturb the circulation system and cause potential brain hypoperfusion, even if the anti-G support protects against G-induced loss of consciousness. Methods Dependency of +Gz magnitude, hemodynamic changes, renal sympathetic nerve activity (RSNA), and aortic blood flow (AoBF) were estimated in anesthetized rats to analyze the effects of +Gz stress and/or an anti-G support on arterial pressure at a level of the brain (APLB). The rats were exposed to +Gz using a centrifuge for small animals while wearing an anti-G suit. Results APLB remained at the control level while the anti-G suit was inflated. However, a decrease in APLB was observed twice during increasing and decreasing G phases using the anti-G suit. Hypotension in the decreasing C phase at +5 Gz was significantly deeper than that in the increasing G phase (47.5 +/- 7.7 vs. 29.6 +/- 3.0 mmHg). RSNA responses to Gz loads were greater in the decreasing G than in the increasing G phase (129.7 +/- 8.6 vs. 147.3 +/- 10.4%). Both AoBF and calculated vascular resistance were suppressed more significantly in the decreasing G than in the increasing G phase (38.3 +/- 4.4 vs. 34.4 +/- 3.4 ml x min(-1), 1.44 +/- 0.22 vs. 1.09 +/- 0.14 mmHg x min(-1) x ml(-1)). Discussion We conclude that transient excessive decreasing G hypotension may occur during the decreasing G phase, which may be due to anti-G suit functioning.

Alvarado C G, Maruyama S, Cheng J, Ida-Yonemochi H, Kobayashi T, Yamazaki M, Takagi R & Saku T (2011) Histopathology59, 283–291 Nuclear translocation of β-catenin synchronized with loss of E-cadherin in oral epithelial dysplasia with a characteristic two-phase appearance Aims: One of the important histopathological characteristics of oral epithelial dysplasia is a two-phase appearance of rete processes, comprising an upper layer of keratinized cells and a lower layer of basaloid cells, and thereby creating a sharp contrast between these two separate cell populations. The aim of this study was to determine the cellular adhesion status of the basaloid cells. Methods and results: Immunohistochemistry for β-catenin, E-cadherin and their related molecules was carried out in surgical specimens of two-phase epithelial dysplasia of the oral mucosa. The lower-half basaloid cells and the upper keratinized cells were microdissected separately, and extracted DNA samples were subjected to methylation-specific polymerase chain reaction amplification for E-cadherin. β-Catenin was immunolocalized within the nuclei and cytoplasm of Ki67-positive lower-half basaloid cells, as well as on the cell membrane of upper parakeratotic cells. The basaloid cells of the lower-half were also positive for matrix metalloproteinase-7 and cyclin D1, β-catenin target gene products, α-dystroglycan, tenascin-C, and perlecan, but not for E-cadherin. The promoter region of the E-cadherin gene was hypermethylated. Conclusions: The solid proliferation of lower-half E-cadherin-free basaloid cells is enhanced by Wnt signalling cascades, as well as by the intraepithelial extracellular matrix or its bound growth factors.

We have developed a new conceptual LCD with a memory circuit and a photo-sensor in each pixel. This LCD enables to display a still image in the low power consumption. In addition, direct writing and erasing a character in the LCD are available without calculating coordinates by using a light pen.

Introduction High positive acceleration (+Gz) stress is known to cause cerebral hypoperfusion, resulting in brain insults. Muscular contraction is reported to induce a pressor response. The effects of teeth clenching on cerebral hypoperfusion were examined. Methods The masseter muscle of anesthetized Sprague-Dawley rats was electrically stimulated to cause maximum clenching of the teeth. Arterial pressure at the level of the brain (APBr), heart rate, and central venous pressure were measured when rats were exposed to +1.5 Gz by using a centrifuge without an anti-C system. Results Acceleration of +1.5 Gz decreased APBr by 18.3 +/- 2.0 mmHg, which was reduced to 1.9 +/- 2.0 mmHg by masseter muscle contraction, but was not reduced by femoral muscle contraction. Stimulation of the masseter muscle but not the femoral muscle induced a pressor response of 11.8 +/- 2.1 mmHg, which was eliminated by dantrolene, a postsynaptic skeletal muscle relaxant. When masseter contraction was blocked by dantrolene, masseter stimulation did not reduce cerebral hypotension in the presence of +1.5-Gz acceleration (delta 18.9 +/- 2.6 mmHg). Conclusion Our results suggest that teeth clenching induced a pressor response that prevented +Gz-induced cerebral hypotension, which suggests the possible development of a new anti-G method.

For histopathological assessment of oral borderline malignancies, it is important to carefully detect subtle epithelial changes on fully stretched tissue sections. However, it is not generally easy to obtain wrinkle-free sections when using formalin-fixed paraffin-embedded oral mucosal samples. Since acetic acid treatment is already utilized for large brain tissue sections, we examined whether that treatment was also effective for oral mucosal tissues containing normal to malignant epithelial lesions. Paraffin sections were floated in various concentrations of acetic acid for 10 min after stretching in water for 1 min, then wrinkle formations were examined using hematoxylin and eosin staining, as well as for staining intensity with keratin immunohistochemistry. Wrinkles were formed in both epithelial and connective tissue zones of sections treated with less than a 40-mM (0.25%) concentration of acetic acid. In contrast, treatments with concentrations at 80 mM (0.5%) and higher resulted in cracking between the epithelial layer and lamina propria, as well as poor immunohistochemical results for keratins 13 and 17, even though the wrinkles completely disappeared. These results indicate that 40 mM is the optimal concentration of acetic acid solution to prevent wrinkles in the epithelial layer while maintaining the immunohistochemical qualities of oral mucosa tissue sections, especially those containing borderline malignant epithelial lesions.

We report a newly developed equivalent electrical circuit for microelectromechanical systems (MEMS) based on a circuit simulator Qucs (Quite Universal Circuit Simulator). An analog computing solver for the equation of motion (EOM) has been interpreted to an electrical equivalent circuit by using an electrical capacitor as an ideal mathematic integrator. Viscoelastic suspension and electrostatic parallel-plate actuator are modeled as equivalent subcircuits that can be cosolved with the EOM module. Those subcircuit models are used as building blocks to numerically simulate the behavior of various types of MEMS actuators. Thanks to the well-prepared simulation toolbox of Qucs, multiphysics analysis of micromechanical and electrical quantities has become straightforward on a single platform. Equivalent circuit models for coupled oscillator and parallel-plate electrostatic actuator (including mechanical contact after electrostatic pull-in) are presented as a verification program to examine the simulation accuracy.  2011 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.

Peculiar findings of orofacial actinomycosis mimicking the clinical appearance of a tumor of the upper lip were reported. A 68-year-old woman (case 1) and a 62-year-old woman (case 2) visited our hospitals towards the end of 2004 and 2007; the clinical diagnosis for each patient was upper labial tumor, and the lesions were surgically removed. Histologically, the excised specimens showed granulomas including bacterial colonies consisting of club-shaped filaments that formed a radiating rosette pattern in the submucosal layer. DNA samples were extracted from paraffin sections and examined by PCR for Actinomyces species. The PCR products examined by direct DNA sequencing demonstrated the presence of Actinomyces israelii and Actinomyces gerencseriae in both case 1 and case 2. Finally, pathological diagnoses of actinomycosis were made for each. Actinomycosis mimicking a tumor is very uncommon in the oral mucosa, and the use of PCR is an effective means of early and accurate diagnosis.

J Oral Pathol Med (2011) 40: 552–559 Objectives: The deposition of perlecan, a heparan sulfate proteoglycan, is enhanced within oral carcinoma in situ (CIS) foci, while it dynamically switches from CIS foci to the stromal space in squamous cell carcinoma (SCC). Because α-dystroglycan and integrin β1 have been identified as two of the perlecan receptors, we wanted to determine their differential distributions before and after invasion of oral SCC. Methods: Eighty-two surgical tissue specimens of oral SCC containing different precancerous stages were examined by immunohistochemistry for perlecan, α-dystroglycan, integrin β1, and Ki-67. In addition, α-dystroglycan mRNA signals were localized by in situ hybridization. Results: In normal epithelia, α-dystroglycan and integrin β1 were localized on the cell membrane of basal cells, while perlecan was faintly present in the intercellular spaces of parabasal cells. In epithelial dysplasia and CIS, α-dystroglycan and perlecan were well co-localized in the epithelial layer, especially in its lower half, and this co-localization was mostly overlapped with Ki-67-positive (+) cell zones. However, in SCC, α-dystroglycan was localized neither within carcinoma cell nests nor in the stroma, while perlecan disappeared from SCC foci but emerged in the stromal space, leaving integrin β1+ and Ki-67+ cells only to the periphery of SCC foci. α-Dystroglycan mRNA signals were basically identical to the α-dystroglycan protein localizations. Conclusion: The findings suggest that α-dystroglycan and integrin β1 act as perlecan receptors in oral precancerous lesions prior to invasion, and that the perlecan signals via the two different receptors function in cellular differentiation and proliferation of CIS cells, respectively.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma, mainly affecting elderly population. Treatment of elderly patients is challenging, and many clinical trials have been conducted to identify the optimal strategy. While rituximab plus CHOP (R-CHOP) therapy is considered as the standard, elderly patients are often frail and sometimes unable to tolerate the standard dose of CHOP therapy. In our institution, 5/6 (83%) and 7/12 (58%) doses of standard CHOP have been administered for patients aged 65-79 years and aged 80 or older, respectively. To evaluate the efficacy and tolerability of our reduced-dose R-CHOP therapy, we conducted a retrospective analysis of 100 patients with median age of 74 (65-86) years and presented the results in ASH 2016 meeting (Ono et al., abstract #4211). The outcome was quite satisfactory. In summary, the overall response rate (ORR) was 93%, and the complete response (CR) rate was 81%. Three-year overall survival (3-yr OS) was 78%. These results seem to be better than the outcome of LNH-98.5 trial (median age 69 years, ORR 83%, CR 75%, 2-yr OS 70%, Coiffier et al., NEJM 2002) and LNH03-6B trial (median age 70 years, ORR 86%, CR 74%, 3-yr OS 72%, Delarue et al., Lancet Oncol 2013), in which 8 cycles of standard-dose R-CHOP were scheduled for patients older than 60 years. There was no significant difference in patient characteristics between our data and those big trials. To find out factors that could play an important role in achieving this favorable outcome, we performed an additional analysis of our data. Methods: We applied the same database that we previously analyzed for ASH 2016. This database included clinical information of 100 patients aged 65 years or older with newly diagnosed DLBCL, who underwent R-CHOP therapy from August 2010 to December 2013 in our institution. We calculated relative dose intensity (RDI) from the doses of cyclophosphamide and doxorubicin and the intervals between each course compared with the standard dose (750 mg/m2 cyclophosphamide and 50 mg/m2 doxorubicin every 21 days). Comorbid conditions were classified by Charlson comorbidity index (CCI). We also analyzed time from diagnosis to initiation of chemotherapy (diagnosis to treatment interval; DTI) in 81 patients. Results: As previously reported, 14 patients were very elderly (≥80 years old) and 57 and 5 patients had an International Prognostic Index (IPI) score of at least 3 and CCI score of at least 3, respectively. Scheduled cycles of R-CHOP were completed in 87 patients and the median RDI was 0.81 in patients aged 65-79 years and 0.58 in patients aged 80 or older. Reduced-dose R-CHOP described above was completed as planned in most of patients. Survival predictors were analyzed using univariate analysis followed by Cox regression model. Multivariate analysis demonstrated that age and RDI had no significant impact on OS. Instead, the independent factors negatively impacting on OS were IPI score ≥3 (p < 0.001), CCI score ≥3 (p = 0.03), incidence of febrile neutropenia (p = 0.04) and not completing the scheduled cycles of R-CHOP (p = 0.001). The median DTI was 17 days. Patients with higher IPI score tended to receive chemotherapy immediately after diagnosis (p = 0.002). Patients with delay in therapy (DTI ≥17 days) had a better outcome (2-year OS was 97% vs. 72%, p = 0.02). Conclusion: In general, older age and low RDI are accepted as the negative prognostic factors. However, they had no impact on OS in this study. The current findings suggest that the completion of 6 or more cycles of R-CHOP plays an important role in achieving a better outcome even when the dose of CHOP is reduced. Although full-dose R-CHOP is still golden standard in the treatment of DLBCL, the appropriate dose reduction can be considered for older and frail patients. Disclosures No relevant conflicts of interest to declare.

Tsuneki M, Yamazaki M, Cheng J, Maruyama S, Kobayashi T & Saku T (2010) Histopathology57, 806–813 Combined immunohistochemistry for the differential diagnosis of cystic jaw lesions: its practical use in surgical pathology Aims: Histopathological distinction of cystic jaw lesions, including odontogenic tumours, is challenging because their lining epithelia, which are basically stratified squamous epithelia, resemble each other, especially when they become hyperplastic from inflammatory reaction. The aim of this study was to seek practical measures to differentiate such lesions. Methods and results: Nineteen surgical specimens from unicystic ameloblastomas (UAs), 17 from keratocystic odontogenic tumours (KCOTs), 13 from dentigerous cysts (DCs), 10 from lateral periodontal cysts (LPCs) and 20 from radicular cysts (RCs), all of which contained both typical flat and rete-peg-shaped lining epithelia, were examined for their immunohistochemical profiles. Among them, keratin (K) 10, K17, perlecan, proliferating cell nuclear antigen (PCNA) and UEA-I lectin binding (UEA) were selected as useful immunohistochemical markers for their differential diagnosis. K10 was positive (+) in KCOT and DC. K17 was not present in RC. Perlecan was found in UA, KCOT and LPC. PCNA+ cells were found frequently in UA and KCOT. These localization patterns were constant even when linings were not flat. Conclusions: Using a combination of six kinds of immunohistochemical pattern, it is now possible to discriminate reliably and objectively these five cystic jaw lesions in routine practice.

J Oral Pathol Med (2011) 40: 20–26 The occurrence of oral cancer is not clearly known in Myanmar, where betel quid chewing habits are widely spread. Since betel quid chewing has been considered to be one of the important causative factors for oral cancer, the circumstantial situation for oral cancer should be investigated in this country. We surveyed oral cancer cases as well as whole body cancers from two cancer registries from Yangon and Mandalay cities, both of which have representative referral hospitals in Myanmar, and we showed that oral cancer stood at the 6th position in males and 10th in females, contributing to 3.5% of whole body cancers. There was a male predominance with a ratio of 2.1:1. Their most frequent site was the tongue, followed by the palate, which was different from that in other countries with betel quid chewing habits. About 90% of male and 44% of female patients had habitual backgrounds of chewing and smoking for more than 15 years. The results revealed for the first time reliable oral cancer frequencies in Myanmar, suggesting that longstanding chewing and smoking habits are etiological backgrounds for oral cancer patients.

To assess sympathetic variability in chronic heart failure (CHF), we evaluated a distribution of inter-spike intervals (ISIs) in renal sympathetic nerve activity (RSNA) in salt-sensitive hypertension-induced CHF (DSSH-CHF) rats. Dahl salt-sensitive rats were fed an 8% NaCl diet for 9 weeks to induce salt-sensitive hypertension-induced CHF. ISIs in RSNA were obtained from chronically instrumented conscious rats, and counts (frequency) and ranks of ISIs in RSNA were plotted with a histogram. We found that ISIs in RSNA followed a power-law distribution in rats, and the power-law distribution of ISIs for RSNA in DSSH-CHF rats was significantly different from that in normal rats. These results indicated that sympathetic variability may be significantly different between salt-sensitive hypertension-induced CHF and healthy individuals, which suggests that sympathetic variability may be used to predict abnormality of the sympathetic regulatory system.

Overall modes of differential gene expressions were analyzed between human oral/salivary carcinoma cell systems with (MK-1 and ACCM) and without (ZK-1/ZK-2 and ACC2/ACC3) metastatic potential by using micro-array analysis with cancer-associated DNA chips to determine the kinds of genes associated with metastatic behaviors. MK-1 and/or ACCM showed lower levels of gene expression in extracellular matrix-related molecules, such as collagen type IV, laminin, and adhesion molecules such as cadherin 2, but higher levels of genes which control extracellular matrix degradation, such as MMP 9, as well as cell growth and cycle, such as FGF7 and cyclin D1. Among the differentially expressed genes, similar protein expression tendencies for FGF7, laminin, cyclin D1, and collagen type IV were confirmed by immunofluorescence. Metastatic potentials of oral/salivary carcinoma cells seem to have resulted from certain combinations of over-/underexpression of the genes, which were responsible for extracellular matrix metabolism and cell growth in particular.

症例は妊娠16週の32歳，女性．下腹部痛で近医を受診し切迫早産の診断で入院した．子宮収縮抑制剤で治療されたが軽快せず，発症7日目に腸閉塞を疑われ当院へ緊急搬送された．腹膜刺激症状を認め，腹部・骨盤部造影CT検査で直腸S状部から上部直腸での腹腔内への腸管内容物の漏出とその周囲の腹腔内遊離ガス像・腹水を認め，直腸穿孔による急性汎発性腹膜炎と診断し緊急手術を施行した．腫大した子宮で穿孔部位の同定は困難であり，ドレナージ・横行結腸人工肛門造設術を施行した．同日破水し自然流産したが，術後46病日に退院した．本症例は妊娠中の便秘が直腸穿孔の原因であったと考えられた．妊婦の直腸穿孔はまれであり，若干の文献的考察を加え報告する．

We report a rare case of central Schwannoma, a type of nerve sheath tumor, arising in the mandibular bone of a 34-year-old man. A periapical lesion was discovered during routine dental treatment. Radiographically, the lesion was a large round-shaped and well-defined radiolucent lesion with a radiopaque rim in the anterior apical region, which extended from the right canine to the left lateral incisor in the mandible. The surgically removed mass was a relatively well-encapsulated tumor, measuring 1.5 cm in diameter. Histologically, the tumor showed a typical histology of Antoni type A of Schwannoma, focally interspersed with myxoid areas in which tumor cells had nuclear atypia. A review of the literature revealed that there have been only a total of 54 reported cases of central Schwannoma of the jaw bones including the present case, most of which were located in the posterior part of the mandible with a female/male ratio of 1.6 to 1 and a mean age of 33.9 years.

Solitary fibrous tumor (SFT) is an uncommon spindle-cell neoplasm of mesenchymal origin. Because the pathogenetic background of SFT is still controversial, cytogenetic analysis could help in tumor diagnosis and prognosis. In this study, cultured SFT cells from a lower lip lesion that presented characteristic immunopositivity for CD34, vimentin, CD99, and BCL2 showed a unique cytogenetic finding: 46,XX,inv(2)(p21q35),t(3;12)(q25;q15). To our knowledge, this is the third report of cytogenetic result of a case involving the oral cavity. The SFT cells in culture that maintained their immunohistochemical expression of diagnostic molecules, showed unique chromosomal changes previously unreported when compared with already documented ones. Our data suggest that the complicated pathogenetic nature of SFT is possibly tumor- or organ-related.

Peripherally secreted arginine vasopressin (AVP) plays a role in controlling body fluid homeostasis, and central endogenous AVP acts as a neurotransmitter or neuromodulator. The limbic system, which appears to exert an inhibitory effect on the endocrine hypothalamus, is also innervated by fibres that contain AVP. We examined whether central endogenous AVP is also involved in the control of body fluid homeostasis. To explore this possibility, we examined neuronal activity in the paraventricular nucleus of the hypothalamus (PVN), periventricular parts of the PVN and limbic brain areas, as well as AVP mRNA expression in the PVN and the peripheral secretion of AVP after central salt-loading in rats that had been pretreated i.c.v. with the AVP V 1 receptor antagonist OPC-21268. Neuronal activity in the PVN evaluated in terms of Fos-like immunoreactivity (FLI), especially in the parvocellular subdivisions, was suppressed. On the other hand, FLI was enhanced in the lateral septum, the bed nucleus of the stria terminalis and the anterior hypothalamic area. Similarly, AVP mRNA expression was enhanced in the magnocellular subnucleus of the PVN, despite the lack of a significant difference in the peripheral AVP level between OPC-21268- and vehicle-pretreated groups. We recorded renal sympathetic nerve activity (RSNA) as sympathetic nerve outflow during central salt-loading. The suppression of RSNA was significantly attenuated by i.c.v. pretreatment with OPC-21268. These results suggest that the suppression of RSNA during central salt-loading might be the result of a decrease in neuronal activity in the parvocellular subdivisions of the PVN via the inhibitory action of central endogenous AVP. The parvocellular and magnocellular neurones in the PVN might show different responses to central salt-loading to maintain body fluid homeostasis as a result of the modulatory role of central endogenous AVP.

Initial irreversible capacity loss in graphite electrodes was suppressed by 1,3,2-dioxathiolane-2,2-dioxide and its derivatives (cyclic sulfates) in propylene carbonate (PC) containing electrolyte. Cyclic voltammetry (CV) showed that cyclic sulfates were decomposed at higher potentials than that for electrolyte solvents. In galvanostatic charge and discharge measurement, first cycle efficiency was increased from 58.2% to 90.5% by the addition of 1,3,2-dioxathiolane-2,2-dioxide. Passivation films formed by cyclic sulfates were observed by X-ray photoelectron spectroscopy (XPS), FT-IR, and pyrolysis/GC/MS (pyro/GC/MS). These results indicate that the surface was covered by a PEO like polymer with the inner layer comprised of Li2S like compounds.

The effect of alkali function group contained in electrode binder was investigated. Carboxy methyl cellulose (CMC) improved the initial irreversible capacity loss in graphite negative electrode. Lithium acetate also improved the initial cycle efficiency. On the other hand, ethyl cellulose (EC) and hydroxyl propyl methyl cellulose (HPMC), which do not have a carboxylic group, did not decrease the reductive electrolyte decomposition. After charge and discharge cycle, the surface film composition on the electrode with CMC was less than on the electrode without CMC. This suggests that a carboxylic group in the binder acted as a catalyst and promoted the solid electrolyte interphase (SEI) formation which prevents the excess electrolyte decomposition on the graphite electrode.

Sixty-four cases of lymphoepithelial cysts of the parotid gland, the largest scale collection in the literature, were clinicopathologically analyzed for their possible pathogenesis. All 64 cases were unilateral, 27 left and 37 right. There were 28 male and 36 female patients with a ratio of 1:1.3. The mean age of the patients was 52.0 years, and their average duration of symptoms was 29.3 months. The mean longest diameter of the cysts was 3.0 cm. Histologically, lymphoepithelial cysts were classified into 3 subtypes: type I, a cystic dilation of ducts within parotid glands (9 cases, 14.1%); type II, partially demarcated cystic lesions with lymphoid stroma (27, 42.2%); type III, well-encapsulated cystic lesions with lymphoid stroma containing lymph follicular structures (28, 43.8%). Based on immunohistochemical results for lymphocyte/macrophage (CD20/CD45RO/IgG4), cell cycle (Ki-67), and lymphatic (D2-40) markers, the lymphoid stroma was shown to have neither the usual lymph follicular distributions of T/B cells nor lymph sinus structures. No viral infection was confirmed. The results seemed to indicate that the lymphoid stroma were induced along with the growth of the cystic dilatation of ducts within sialadenitis, which were neither induced by Epstein-Barr virus nor HIV infections, and that the formation of lymphoepithelial cysts was completed by demarcation, which should have been a kind of granulation tissue reaction, from the parotid parenchyma but did not arise from intraparotid lymph nodes.

Background: As one of the valuable tools for differential diagnoses of oral epithelial dysplasia, carcinoma in situ (CIS) and squamous cell carcinoma (SCC), we have proposed the immunohistochemistry for perlecan, a heparan sulfate proteoglycan (HSPG). As HSPGs have been shown to be extracellular docking molecules for matrix metalloproteinase (MMP) 7, our aim was to determine the expression mode of MMP-7 in these lesions for its possible diagnostic aid for oral borderline malignancies. Methods: Twenty cases each of moderate dysplasia, CIS, SCC, and normal/hyperplastic/mild dysplastic epithelia of the tongue and buccal mucosa were immunohistochemically examined for MMP-1, -2 and -7 in reference to their perlecan immunolocalization. Results: The expression of all three MMPs in the normal mucosal epithelium was restricted mainly to the parabasal layers. The most striking finding was strong expression of MMP-7 in epithelial dysplasia with a two-phase appearance: a clear demarcation of MMP-7-immunopositive (+) lower dysplastic/basaloid cells from non-positive upper keratinized cells. MMP-7+ cells were spread over the whole epithelial layer of CIS. In SCC, MMP-7 positivity was reduced from carcinoma cells but instead appeared in stromal cells. These expression profiles of MMP-7 resembled those of perlecan. MMP-1 and MMP-2 exhibited a similar but much weaker staining than MMP-7. Conclusion: These results suggest that the enhanced metabolism of perlecan associated with MMP-7 plays an important role in the cell proliferation of oral epithelia in their malignant transformation process, and that MMP-7 immunohistochemistry may be a valuable aid for identification of the cell proliferation center in oral CIS and dysplasia.

BACKGROUND: Capsular invasion is often observed in daily pathologic diagnosis of pleomorphic adenomas, although neither actual information about its occurrence nor molecular mechanisms leading to their invasive activities have been reported. In this study, our aim was to elucidate the mode and the frequency of capsular invasion in this tumor and to characterize the tumor cell arrangement at the site of capsular invasion. METHODS: The mode and frequency of capsular invasion of salivary pleomorphic adenomas were histopathologically examined in 104 surgical specimens of pleomorphic adenoma, and stromal characteristics, and tumor cell arrangements at the sites of capsular invasion were immunohistochemically investigated. RESULTS: A total of 353 areas with capsular invasive changes were collected from 104 cases. The mode of capsular invasion was classified into two types: type I: intra-capsular invasion (247 areas, 70%) and type II: capsular penetration (106 areas, 30%). Myxoid stroma, which was perlecan-immunopositive (+), was shared by both type I and type II sites, while tumor cell foci containing ductal structures were predominant in type II sites. These foci were composed of KGF + and FGFR2 + cells. In addition, apparent vascular involvement was recognized in 31 tumors (29.8%). CONCLUSION: The results suggest that pleomorphic adenoma cells are able to invade into the capsule and involve blood vessels when they are situated in perlecanrich milieu, which accelerate KGF signaling.

Nerve sheath myxoma is a rare benign tumor of nerve sheath origin that typi­ cally presents as a small solitary skin nodule and rarely affects the oral cavity. A case of nerve sheath myxoma of the tongue in a 51­year­old male is reported. The patient had a painless submucosal nodule in the lateral margin of the tongue for several months. The tumor was surgically removed under local anesthesia. Histopathologically, the removed tumor consisted of several loosely textured myxofibrous nodules in which spindle­ or stellate­shaped cells with eosinophilic cytoplasm and hyperchromatic nuclei were scattered. Immunohistochemically, the myxoid stroma was strongly positive for perlecan, a basement membrane type heparan sulfate proteoglycan, and the tumor cells were individually circumscribed by type IV collagen­positive fibers. In addition, the tumor cells were strongly positive for vimentin, S­100 protein, neuron­ specific enolase, and cathepsin D. However, they were not positive for epithelial membrane antigen, neurofilament protein, CD34, CD10, calponin, actin, or any subtypes of keratin. A review of the literature revealed that 11 cases of oral nerve sheath myxoma had been documented. The mean age of the patients was 29 years old, and there was no predilection between males and females. They arose most frequently in the tongue. (Oral Med Pathol 2009; 13: 105-110 doi: 10.3353/omp.13.105)

Since the risks of development of salivary mucoepidermoid carcinoma and Warthin tumor have been significantly greater among atomic bomb survivors in a dose-dependent manner, the p53 gene, an important proto-oncogene whose mutation has been related to radiation, was analyzed by DNA sequencing and immuno- histochemistry in 37 cases of mucoepidermoid carcinoma collected from Niigata and Nagasaki and in 33 cases of Warthin tumor collected from Niigata. Immunohis- tochemically, p53 gene products were heavily demonstrated in most of the tumor cell nuclei of mucoepidermoid carcinomas but not in Warthin tumors. Mucoepidermoid carcinomas had some point mutations (codons 136-137, 144, 232, 234, and 241) but their incidences among the samples were not significantly high (2.7%-10.8%). In contrast, three point mutations (codons 143, 151, and 229) were commonly found in the Warthin tumor cases (80%-87%), but the former two mutations did not alter their amino acid composition. Thus, there were no p53 mutations which were shared by the two tumors. However, the mutations at exon 5 of mucoepidermoid carcinomas were significantly higher in the cases from Nagasaki than those from Niigata, although their highest frequencies at most were around 10%. The results suggest that point mutations of p53 gene, as far as exons 5-7 were concerned, do not play any obviously important roles in the radiation-based tumorigenetic processes shared by mucoepi- dermoid carcinoma and Warthin tumor. (Oral Med Pathol 2009; 13: 151-158 doi: 10.3353/omp.13.151)