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Instruction The human amphoterin-induced gene and open reading frame (AMIGO) was identified as a novel cell adhesion molecule of type I transmembrane protein. AMIGO2 is one of three members of the AMIGO family (AMIGO1, 2, and 3), and the similarity between them is approximately 40% at the amino acid level. We have previously shown that AMIGO2 functions as a driver of liver metastasis. Immunohistochemical analysis of AMIGO2 expression in colorectal cancer (CRC) using a commercially available anti-AMIGO2 mouse monoclonal antibody clone sc-373699 (sc mAb) correlated with liver metastasis and poor prognosis. However, the sc mAb was found to be cross-reactive with all three molecules in the AMIGO family. Methods We generated a rat monoclonal antibody clone rTNK1A0012 (rTNK mAb) for human AMIGO2. The rTNK mAb was used to re-evaluate the association between AMIGO2 expression and liver metastases/clinical outcomes using the same CRC tissue samples previously reported with sc mAb. Results Western blot analysis revealed that a rTNK mAb was identified as being specific for AMIGO2 protein and did not cross-react with AMIGO1 and AMIGO3. The rTNK mAb and sc mAb showed higher AMIGO2 expression, which correlates with a high frequency of liver metastases (65.3% and 47.5%, respectively), while multivariate analysis showed that AMIGO2 expression was an independent prognostic factor for liver metastases (p = 7.930E-10 and p = 1.707E-5). The Kaplan-Meier analyses showed that the rTNK mAb (p = 0.004), but not sc mAb (p = 0.107), predicted worse overall survival in patients with high AMIGO2 expression. The relationship between AMIGO2 expression and poor disease-specific survival showed a higher level of significance for rTNK mAb (p = 0.00004) compared to sc mAb (p = 0.001). Conclusions These results indicate that the developed rTNK1A0012 mAb is an antibody that specifically recognizes AMIGO2 by immunohistochemistry and can be a more reliable and applicable method for the diagnostic detection of liver metastases and worse prognosis in patients with high AMIGO2-expressing CRC.

【Background】Indirubin, a constituent of the Chinese herbal medicine “Qing-Dai,” has anti-cancer and anti-inflammatory activities. We aimed to evaluate the efficacy of indirubin for ameliorating colonic inflammation in a mouse model of inflammatory bowel disease. 【Methods】Mice with dextran sulfate sodium (DSS)induced acute and chronic colitis were treated with indirubin in their diet. Clinical and histologic changes were evaluated. In addition, colon levels of interleukin-6, a critical pro-inflammatory mediator, was detected by enzyme-linked immunosorbent assay. 【Results】In the model of acute colitis, indirubin treatment improved the loss of body weight. Histology of colonic tissue revealed that indirubin treatment improved the histology grading of colitis (P = 0.02), the extent of submucosal fibrosis (P = 0.018), the number of mucosal toluidine blue-positive cells (P = 0.004) and colon length (P = 0.01). In the model of chronic colitis, indirubin treatment had no significant effect on pathologic findings except for colon length (P = 0.003). However, indirubin administration significantly reduced colon levels of interleukin-6 in the chronic-colitis model (P = 0.001). 【Conclusion】Our study clearly showed that oral intake of indirubin can improve murine DSS-induced colitis (which mimics human inflammatory bowel disease).

Extensive studies on metastasis-associated proteins, S100A4 and MTA1, have been carried out for over two decades, but correlation of both proteins remains obscure. Here we show evidence for the correlation in angiogenesis. First, silencing of each protein by siRNA-mediated knockdown in mouse endothelial MSS31 cells resulted in the inhibition of tube formation. Unexpectedly, the knockdown of MTA1 affected not only its own expression but also the expression of S100A4, whereas silencing of S100A4 did not affect the MTA1 expression. Additionally, non-muscle myosin IIA (NMIIA) phosphorylation, which was partly controlled by S100A4, was found to be upregulated by knockdown of both proteins in MSS31 cells. Moreover, cycloheximide treatment of MSS31 cells revealed that the rate of S100A4 degradation was accelerated by MTA1 knockdown. This finding, together with our observation that cytoplasmic MTA1, but not nuclear MTA1, was colocalized with S100A4, suggested the involvement of MTA1 in S100A4 stability. The direct in vivo angiogenesis assay showed that both protein siRNAs provoked a significant inhibition of new blood vessel formation induced by angiogenic factors, indicating their anti-angiogenic activities. Treatment of human pancreatic tumor (PANC-1) xenograft in mice with mMTA1 siRNA resulted in tumor regression via suppression of angiogenesis in vivo, as also observed in the case of human prostate cancer xenograft treated with mS100A4 siRNA. Taken together, these data led us to conclude that the MTA1-S100A4-NMIIA axis exists in endothelial cells as a novel pathway in promoting tumor vascular formation and could be a target for suppressing tumor growth and metastasis.

H. Muraoka1, H. Asanuma2, N. Tsuchiya3, T. Ito4, T. Mogi5, H. Ito6, and the participants of the ICDP/JBBP Workshop 1North Japan Research Institute for Sustainable Energy, Hirosaki University, Matsubara 2-1-3, Aomori 030-0813, Japan 2Renewable Energy Research Center, AIST, Central 7, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8567, Japan 3Graduate School of Environmental Studies, Tohoku University, Aoba 6-6-20, Miyagi 980-8579, Japan 4Institute of Fluid Science, Tohoku University, Katahira 2-1-1, Aoba-ku, Sendai 980-8577, Japan 5Graduate School of Sciences, Hokkaido University, Kita 10, Nishi 8, Kita-ku, Sapporo 060-0810, Japan 6Independent scientist, Japan

The Marmara section of the North Anatolian Fault Zone (NAFZ) runs under water and is located less than 20 km from the 15-million-person population center of Istanbul in its eastern portion. Based on historical seismicity data, recurrence times forecast an impending magnitude M>7 earthquake for this region. The permanent GONAF (Geophysical Observatory at the North Anatolian Fault) has been installed around this section to help capture the seismic and strain activity preceding, during, and after such an anticipated event.

BackgroundAirway remodelling in bronchial asthma (BA) and COPD has been quantitatively assessed by analysing the airway wall area and the luminal area on cross-sectional CT images. To date, there have been no reports on assessment of the longitudinal structure of the airway lumen.MethodsQuantitative airway analysis using CT was performed on three groups consisting of 29 patients with BA, 58 patients with COPD and 59 healthy controls. To assess the longitudinal shape irregularity of the airway lumen, new quantitative CT parameters, validated by a phantom study, were established. The internal radii of imaginary inscribed spheres in the airway lumen were measured as a function of distance from the level of the carina to the fifth-order branches of the right posterior basal bronchus. The gaps of these radii from the regression line were calculated as parameters to reflect the longitudinal airway lumen shape irregularity. These new parameters were compared among the study groups as well as with the conventional parameters of airway wall thickening and luminal area.ResultsLongitudinal airway lumen shape irregularity was significantly greater in patients with COPD than in those with BA and healthy controls. Wall thickening was significantly greater, and luminal area smaller, in patients with BA than in those with COPD and healthy controls. These results were consistent even among the BA and COPD subgroups with similar airflow limitation.ConclusionsThe combination of cross-sectional and longitudinal airway structure analyses using CT images may suggest differences in the characteristics of airway remodelling between COPD and asthma.

Pore pressure decreased at the Kamioka mine in central Japan after the Tohoku earthquake (M9.0) on 11 March 2011, which can be attributed to a permeability increase. We focus on the Earth's tidal response before and after the earthquake to evaluate rock permeability change through hydraulic diffusivity change. If we assume a constant elastic modulus, hydraulic diffusivity is found to increase from 3.3 to 6.7 m2/s after the Tohoku earthquake. We also analyzed data before and after the 2007 Noto Hanto (M6.9) and 2008 Suruga Bay (M6.5) earthquakes, which yield no significant tidal response changes. We examined the amount of dynamic and static stress changes caused by these earthquakes and show that it is difficult to attribute the permeability enhancement solely to dynamic stress, and static stress change may also affect the permeability enhancement.

Case A 45-year-old man was brought to our hospital in pre-shock after falling from a motorcycle. As we diagnosed him with open fracture of the right femur with leg ischemia, we performed revascularization of injured popliteal artery and treated the leg. The pathological findings showed fragmentation and decrease of elastic fibers and fragmentation of collagen fibers, but no inflammatory cells or intimal hyperplasia, and no dissection. Outcome Unfortunately, amputation had to be carried out on the 29th postoperative day due to infection and leg dysfunction. The postoperative course was uneventful. The patient could walk with an artificial leg and was discharged approximately 5 months after popliteal artery replacement. Conclusions We report a case of revascularization involving a patient with open fracture of the right femur due to acute blunt popliteal artery injury.

The purpose of this study was to retrospectively evaluate the incidence of delayed renal dysfunction after total body irradiation (TBI) in long-term survivors of TBI/hematopoietic stem cell transplantation (HSCT). Between 1989 and 2006, 24 pediatric patients underwent TBI as part of the conditioning regimen for HSCT at Chiba University Hospital. Nine patients who survived for more than 5 years were enrolled in this study. No patient had any evidence of renal dysfunction prior to the transplant according to their baseline creatinine levels. The median age at the time of diagnosis was 6 years old (range: 1-17 years old). The follow-up period ranged from 79-170 months (median: 140 months). Renal dysfunction was assessed using the estimated glomerular filtration rate (eGFR). The TBI dose ranged from 8-12 Gy delivered in 3-6 fractions over 2-3 d. The patients were treated with linear accelerators in the supine position, and the radiation was delivered to isocentric right-left and left-right fields via the extended distance technique. The kidneys and the liver were not shielded except in one patient with a left adrenal neuroblastoma. No patient required hemodialysis. The eGFR of four patients (44.4%) progressively decreased. The remaining patients did not demonstrate any eGFR deterioration. Only one patient developed hypertension. By evaluating the changes in eGFR, renal dysfunction among long-term survivors of TBI/HSCT could be detected. Our results suggested that the TBI schedule of 12 Gy in 6 fractions over three consecutive days affects renal function.

Proliferative fasciitis (PF) is a benign, discrete proliferation of fibroblasts or myofibroblasts in soft tissue. Proliferative fasciitis mostly occurs in adults and is often confused with a sarcoma because of its rapid growth and peculiar histological features. We report a case of PF mimicking a sarcoma which developed in a 13-year-old boy, who noticed a painful tumor, with gradual enlargement, in his right lower leg. Magnetic resonance imaging revealed that the tumor measured 34 mm × 20 mm × 41 mm and was located in the subcutaneous tissue. The tumor was surgically resected. Pathologically, the tumor was composed of a proliferation of atypical spindle cells, admixed with larger ganglion-like cells. Immunohistochemically, the tumor cells were positive for vimentin, cytokeratin, smooth muscle actin, HHF-35 and Fli-1. The tumor was subsequently diagnosed as a PF, although it was difficult to differentiate from a sarcoma. Five years after surgery, the postoperative course has been uneventful with no recurrence or metastasis.

Paired-like homeodomain 1 (PITX1) genes are essential in human development. In the present study, PITX1 protein expression was evaluated in human normal oral mucosa, oral epithelial dysplasia and oral squamous cell carcinoma (OSCC), with the aim of examining the expression patterns of these critical genes during the multi-stage transformation of oral epithelial dysplasia to OSCC. PITX1 and Ki-67 expression were assessed by immunohistochemistry in 26 individuals with normal oral mucosa, 106 patients with oral epithelial dysplasia and 97 OSCC patients. The labeling indices (LIs) of PITX1 and Ki-67 were calculated and their correlation with the incidence of malignancy was evaluated. The PITX1 LI of the dysplasia specimens was significantly lower than that of the normal oral mucosa samples, but significantly higher than that of the OSCC samples. The oral epithelial dysplasia patients that exhibited low PITX1 expression showed a significantly higher incidence of malignant transformation than those exhibiting high PITX1 expression, regardless of the histological grades of their oral epithelial dysplasias. On the other hand, no correlation was observed between the Ki-67 LI and the incidence of malignancy. These results suggested that PITX1 suppression is associated with malignant transformation in the oral epithelium and that PITX1 expression may serve as a novel biomarker for predicting prognosis in oral epithelial dysplasia.

Background: The pituitary homeobox 1 (PITX1) protein is a member of the bicoid-related homeobox transcription factors and has essential roles in human development. Recently, the PITX1 gene has been considered as a tumor suppressor gene in various human cancers. Objective: This study examined the expression of PITX1 in the development and progression of human cutaneous malignant melanoma. Materials & Methods: Immunohistochemical and/or immunofluorescence analyses were performed to examine the histological expression of PITX1 in healthy skin and 40 cutaneous malignant melanoma cases, including 10 melanoma in situ cases. Results: Expression of PITX1 was shown in nuclei of melanocytes in normal skin. PITX1 expression was positive (labeling index: ≥10%) in 21 (52.5%) cases and negative (labeling index

[1] In situ test of hydraulic fracturing (HF) provides the only way to observe in situ stress magnitudes directly. The maximum and minimum horizontal stresses, SHmax and Shmin, are determined from critical borehole pressures, i.e., the reopening pressure Pr and the shut-in pressure Ps, etc, observed during the test. However, there is inevitably a discrepancy between actual and measured values of the critical pressures, and this discrepancy is very significant for Pr. For effective measurement of Pr, it is necessary for the fracturing system to have a sufficiently small compliance. A diagnostic procedure to evaluate whether the compliance of the employed fracturing system is appropriate for SHmax determination from Pr was developed. Furthermore, a new method for stress measurement not restricted by the system compliance and Pr is herein proposed. In this method, the magnitudes and orientations of SHmax and Shmin are determined from (i) the cross-sectional shape of a core sample and (ii) Ps obtained by the HF test performed near the core depth. These ideas were applied for stress measurement in a central region of the Kumano fore-arc basin at a water depth of 2054?m using a 1.6?km riser hole drilled in the Integrated Ocean Drilling Program (IODP) Expedition 319. As a result, the stress decoupling through a boundary at 1285?m below seafloor was detected. The boundary separates new upper layers and old lower ones with an age gap of ~1.8?Ma, which is possibly the accretionary prism. The stress state in the lower layers is consistent with that observed in the outer edge of accretionary prism.

Aims and Objectives: Ethanol is widely used for the embolization treatment of vascular malformations, but it can also cause serious complications such us pulmonary hypertension, cardiopulmonary collapse and death. The complications are considered secondary to pulmonary vasospasm and ethanol-induced sludge embolism, etc., We studied the hemodynamic effects of intravenous absolute ethanol injection and ethanol sludge injection in pigs. Materials and Methods: A total of 5 pigs underwent intravenous injection of ex vivo generated ethanol-induced sludge in which residual ethanol was removed (Group S) and 4 pigs underwent intravenous injection of absolute ethanol (Group E). Hemodynamic parameters related to the pulmonary and systemic circulation were compared between the groups. Results: Transient pulmonary hypertension was observed in both groups and the hemodynamic changes were similar in both groups. Conclusions: Sludge can induce transient pulmonary hypertension or cardiopulmonary collapse, without ethanol and may be the mechanism by which ethanol induces its adverse hemodynamic effects.

This paper presents development of high water-permeable dialysis membranes. We proposed the system that does not use dialysis fluid for the implantable micro dialysis treatment and development of such membranes is crucial. We developed micro dialysis system composed by nanoporous membranes and microfluidic channels in our prior work. The membranes were made of nanoporous polyethersulfone (PES), which was not water-permeable. By not using dialysate, our device can be simplified because the pumps and storage tanks for the dialysis fluid are not necessary. This treatment is termed as hemofiltration. We measured the water permeability of PES membrane with respect to the concentrations of the PES, the additives, and the solvents in the casting solution. We could find the membranes with sufficiently high water permeability through in vitro experiments using a syringe pomp and whole cow blood, and the membrane had enough mechanical strength. We conducted experiments with multi-layered device in in vitro and in vivo using rats, where the system was connected to the vein and artery. We successfully collected the filtrate beyond target line, which was set by a medical doctor, without any leakage of blood from the device. The results verified that the filtration device can be scaled-up by increasing a number of the layer. We connected the device to a rat for 5h. It was verified the device maintained almost constant water permeability beyond our target line.

At present, amino acids are widely produced and utilized industrially. Initially, monosodium glutamate (MSG) was produced by extraction from a gluten hydrolysate. The amino acid industry started using the residual of the lysate. The discovery of the functions of amino acids has led to the expansion of their field of use. In addition to seasoning and other food use, amino acids are used in many fields such as animal nutrients, pharmaceuticals, and cosmetics. On the other hand, the invention of the glutamate fermentation process, followed by the development of fermentation methods for many other amino acids, is no less important. The supply of these amino acids at a low price is very essential for their industrial use. Most amino acids are now produced by fermentation. The consumption of many amino acids such as MSG or feed-use amino acids is still rapidly increasing.

Background and Aim: Abnormal expression of Fragile Histidine Triad (Fhit), E-cadherin and p53 is observed in esophageal squamous cell carcinoma. It has recently been reported that aberrant expression of activation-induced cytidine deaminase (AID) in gastric epithelium leads to the accumulation of nucleotide alterations in the p53 gene. However, little is known about the association between these molecular events and the clinicopathological characteristics of early stage esophageal squamous neoplasia, especially in endoscopically resected tumors. Methods: Esophageal squamous neoplasias (n = 49) comprising nine cases of low-grade intraepithelial neoplasia (LGIN), 22 of high-grade intraepithelial neoplasia/carcinoma in situ (HGIN/CIS) and 18 of invasive cancers, were endoscopically resected. Their expression of the tumor-related proteins: Fhit, E-cadherin, p53 and AID was assessed using immunohistochemical methods, and the relationship between protein expression and clinicopathological data was examined. Results: Reduced or absent Fhit and E-cadherin expression was detected in 22% and 0% of LGIN cases, 73% and 14% of HGIN/CIS cases, and 94% and 61% of invasive cancer cases, respectively, showing progressive increases during neoplastic progression (Fhit: P

Variables A Cross-sectional area of the model (L) a Local aperture of the fracture (L) ai Aperture at the ith voxel (L) CTVi CT value at the ith voxel (Hounsfield unit) f Correction factor for the cubic law equation k Permeability of the model (L) L Length of the model (L) N Total number of voxels P Pressure of the fluid (MLT) DP Pressure difference (MLT) Q Total flow rate (LT) W Local width of the fracture (L)

The pig is an important animal for both agricultural and medical purposes. However, the number of pig-derived cell lines is relatively limited when compared with mouse- and human-derived lines. We established in this study a retroviral conditional expression system for the Simian vacuolating virus 40 large T fragment (SV40T) which allowed us to efficiently establish pig embryonic fibroblast cell lines. The established cell lines showed high levels of cell proliferation and resistance to cellular senescence. A chromosome analysis showed that 84% of the cells had the normal karyotype. Transient expression of the Cre recombinase allowed us to excise the SV40T fragment from the genome. The development of this research tool will enable us to quickly establish new cell lines derived from various animals.

OBJECTIVE To evaluate the incidence and clinical significance of retropharyngeal lymph node metastasis in hypopharyngeal cancer. METHODS Pretreatment computed tomography and/or magnetic resonance images of 152 patients treated between 1998 and 2009 were retrospectively reviewed. The prognostic significance of retropharyngeal lymph node metastasis for 116 patients who received definitive treatment was also analyzed. RESULTS Twelve patients (8%) were radiologically positive for retropharyngeal lymph node metastasis. Tumors originating from the posterior wall showed significantly higher incidence of retropharyngeal lymph node than those originating from other sites (23.8 vs. 5.3%, P = 0.01). The majority of patients with retropharyngeal lymph node involvement experienced distant metastasis. The overall survival rate of patients with retropharyngeal lymph node metastasis was worse than in those lacking retropharyngeal lymph node involvement (0 vs. 68.8% at 2 years, P < 0.01), and so was the cause-specific survival rate (0 vs. 74% at 2 years, P < 0.01). CONCLUSIONS Patients with hypopharyngeal cancer, especially those with posterior wall tumors, are at high risk for retropharyngeal lymph node involvement. Patients with retropharyngeal lymph node metastasis developed distant metastasis frequently, and showed dismal outcomes.

The 21st Hiroshima Cancer Seminar focused on recent progress of carcinogenesis, progression and management of upper gastrointestinal cancers. β-Catenin and p120 mediate peroxisome proliferator-activated receptor δ-dependent proliferation induced by Helicobacter pylori in gastric epithelia. Helicobacter pylori CagA plays an important role in stomach carcinogenesis via altered signal transduction and cell polarity by interactions with several host proteins. Inflammation caused by H. pylori infection is responsible for inducing aberrant DNA methylation. The gastric gland mucin-specific αGlcNAc plays dual roles in preventing gastric cancer, inhibition of H. pylori infection and suppression of tumor-promoting inflammation. Information obtained from transcriptome dissection greatly contributes to understanding the molecular character of each mucin phenotype of gastric cancer. The standardized biomarkers will serve as good predictive and prognostic markers for gastric cancer. A microRNA expression profile may be useful for the diagnosis of gastric cancer. Bone marrow-derived mesenchymal stem cells may provide an advantageous microenvironment for re-acquisition of stemness of gastric cancer cells. Recent progress in molecular biology research has enabled the clinical development of molecular targeting agents for gastric cancer, such as trastuzumab. The target molecule-based inhibition of the stromal reaction in the microenvironment may hold promise as an effective anti-tumor therapy. Since robotic surgery is feasible and safe, and provides adequate and precise lymph node dissection, it may be one of the good options for gastric cancer in the near future.

J Oral Pathol Med (2012) 41: 444–451 Background: Stromal cells are believed to affect cancer invasion and metastasis. The purpose of this study was to evaluate the distribution of cancer-associated fibroblasts (CAFs) and the incidence of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC), focusing on clinicopathological factors and patient prognosis, as well as cancer invasion. Methods: The study included 108 patients with OSCC. Anti-α-smooth muscle actin, CD68, and CD163 antibodies were used to identify CAFs and TAMs. CAFs were divided into 4 grades on the basis of staining intensity: negative (0), scanty (1), focal (2), and abundant (3). The most intensive areas of macrophage concentration in each tumor invasive stroma were also evaluated. Results: The cancer specimens were divided into Grade 0/1, Grade 2, and Grade 3 on the basis of CAF grade. In addition, they were divided into low- and high-grade groups on the basis of the number of CD68-positive and CD163-positive macrophages. The latter were significantly increased in the Grade 2 CAF group compared to the Grade 0/1 group (P = 0.009). Kaplan–Meier and multivariate survival analyses revealed that Grade 2 CAFs (P = 0.003) and high CD163-positive macrophage levels (P = 0.007) significantly correlated with a poor outcome in patients with OSCC, and that a high CD163-positive macrophage level was a significant and an independent prognostic factor (P = 0.045). Conclusions: Cancer-associated fibroblasts and CD163-positive macrophages may be potential prognostic predictors of OSCC.

Aim: The diagnosis of acute liver failure due to autoimmune hepatitis is often difficult because of atypical clinicopathological features. Patients with autoimmune acute liver failure are sometimes resistant to immunosuppressive therapy and have poor prognosis. Although their survival rates are especially poor (5–20%) without liver transplantation in Japan, their clinicopathological features have remained uncertain. A major problem is that there is no gold standard for making the diagnosis of acute onset autoimmune hepatitis. If there are diagnosing tools supporting clinicopathological features, they are of benefit to the patients. We examined computed tomography (CT) imaging features of autoimmune acute liver failure to clarify the usefulness of imaging for the diagnosis. Methods: A retrospective analysis of 129 unenhanced CT scans of 68 patients with acute hepatitis, consisting of 23 with autoimmune acute liver failure (ALF) (group 1), 25 with early admission-viral ALF (group 2) and 20 with late admission-viral ALF (group 3), was performed. Results: Autoimmune acute liver failure showed heterogeneous hypoattenuating areas and viral ALF diffuse ones (P

Extramammary Paget's disease (EMPD) is a rare malignant skin neoplasm. The prototypical pattern of tumor cell proliferation in the epidermis includes single cells and/or nest arrangements, mainly in the lower epidermis. Although other patterns have been recognized, they have not previously been investigated in detail. We aimed to examine the patterns of tumor cell proliferation in the epidermis. Surgical specimens were obtained from 38 patients with primary EMPD. We defined six patterns, in addition to the prototypical one: (i) glandular; (ii) acantholysis-like; (iii) upper nest; (iv) tall nest; (v) budding; and (vi) sheet-like. There were 26 males and 12 females (mean age, 75.0 years). Lesions were located on the scrotum (26 cases) and vulva (12). There were 22 in situ EMPD and 16 invasive EMPD. The frequencies of the different proliferation patterns were: glandular, 36.8%; acantholysis-like, 73.7%; upper nest, 68.4%; tall nest, 28.9%; budding, 47.4%; and sheet-like, 23.7%. Upper nest pattern and the presence of more than three patterns were significantly more frequent in invasive EMPD than in situ EMPD (P < 0.05). We identified the histopathological patterns of Paget cell proliferation in the epidermis in EMPD, and suggest that the characteristic patterns and the diversity of patterns could be associated with progression and dermal invasion in EMPD.

The purpose of our study was to describe the MR appearance of Kimura disease and to interpret the differences in appearance from malignant parotid gland tumours.MR studies of seven patients with Kimura disease were reviewed. The MR studies included T(1) weighted, T(2) weighted, short tau inversion-recovery, diffusion-weighted (DW) and dynamic contrast-enhanced imaging.Typical Kimura disease featured subcutaneous lesions, continuously infiltrated parotid lesions from the subcutaneous lesions with or without intraparotid lymphadenopathies, and reactive cervical lymphadenopathies. The subcutaneous lesions showed gradual upward enhancement on dynamic contrast-enhanced MR images. Reactive lymph nodes showed early enhancement on contrast-enhanced MR images and marked high intensity and low apparent diffusion coefficient values on DW images.An indication for making the diagnosis of Kimura disease should be the subcutaneous tissue of the head and neck showing gradual upward enhancement on dynamic contrast-enhanced MRI and a lack of high intensity on DW images, associated with reactive lymph nodes.

Pulmonary metastases are the main cause of death in patients with osteosarcoma, however, the molecular mechanisms of metastasis are not well understood. To detect lung metastasis-related microRNA (miRNA) in human osteosarcoma, we compared parental (HOS) and its subclone (143B) human osteosarcoma cell lines showing lung metastasis in a mouse model. miR-143 was the most downregulated miRNA (P < 0.01), and transfection of miR-143 into 143B significantly decreased its invasiveness, but not cell proliferation. Noninvasive optical imaging technologies revealed that intravenous injection of miR-143, but not negative control miRNA, significantly suppressed lung metastasis of 143B (P < 0.01). To search for miR-143 target mRNA in 143B, microarray analyses were performed using an independent RNA pool extracted by two different comprehensive miR-143-target mRNA collecting systems. Western blot analyses revealed that MMP-13 was mostly protein downregulated by miR-143. Immunohistochemistry using clinical samples clearly revealed MMP-13-positive cells in lung metastasis-positive cases, but not in at least three cases showing higher miR-143 expression in the no metastasis group. Taken together, these data indicated that the downregulation of miR-143 correlates with the lung metastasis of human osteosarcoma cells by promoting cellular invasion, probably via MMP-13 upregulation, suggesting that miRNA could be used to develop new molecular targets for osteosarcoma metastasis.

The 20th Hiroshima Cancer seminar focused upon breast cancer research and treatment particularly on the mechanism of tumorigenesis and drug resistance and development of novel therapeutics. Several molecules such as retinoblastoma and p16 were raised as key factors in tumorigenesis and invasiveness. Estrogen-related pathways seem to be closely involved in the process. For the tumor lacking hormone receptor and human epidermal growth factor 2, some other mechanisms could be responsible. It seems that MicroRNA 22 directing some putative targets such as SIRT1, Sp1 and CDK6 plays a crucial role in breast tumor growth and metastasis. In addition, ribophorin and the associated molecules might be engaged in breast cancer stemness. Obviously, these molecules provide potential for therapeutic targets. It was also discussed about new drug development such as anti-human epidermal growth factor 2 therapy, anti-angiogenesis, pro-tumor aspects of anti-cancer therapy and application of circulating markers for monitoring, imaging and health-care system. Furthermore, we discussed risk factors, prevention and screening to reduce invasive cancers as well. Throughout the conference, panelists and attendee indicated the importance of translational research and biomarker exploration in order to realize efficient and individualized therapy for breast cancer.

Purpose S-1 is an oral fluoropyrimidine derivative that has demonstrated favorable antitumor activity in patients with metastatic pancreatic cancer. The aim of this study was to evaluate safety and efficacy of S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Methods and Materials Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day at a dose of 80 mg/m 2 /day from day 1 to 14 and 22 to 35. Two weeks after the completion of chemoradiotherapy, maintenance chemotherapy with S-1 was administered for 28 days every 6 weeks until progression. Results Thirty-four patients were enrolled in this study. The most common Grade 3 toxicities during chemoradiotherapy were anorexia (24%) and nausea (12%). The overall response rate was 41% (95% confidence interval, 25%–58%) and overall disease control rate (partial response plus stable disease) was 97%. More than 50% decrease in serum CA 19-9 was seen in 27 of 29 evaluable patients (93%). The median progression-free survival was 8.7 months. The median overall survival and 1-year survival rate were 16.8 months and 70.6%, respectively. Conclusions Oral S-1 and concurrent radiotherapy exerted a promising antitumor activity with acceptable toxicity in patients with locally advanced pancreatic cancer. This combination therapy seems to be an attractive alternative to conventional chemoradiotherapy using 5-fluorouracil infusion.