Attempt to Make the Upper-Limb Item of Objective Fugl-Meyer Assessment Using 9-Axis Motion Sensors.

The Fugl-Meyer Assessment (FMA) has been used as a functional assessment of upper-limb function in stroke patients. This study aimed to create a more objective and standardized evaluation based on an FMA of the upper-limb items. A total of 30 first-ever stroke patients (65.3 ± 10.3 years old) and 15 healthy participants (35.4 ± 13.4 years old) admitted to Itami Kousei Neurosurgical Hospital were included. A nine-axis motion sensor was attached to the participants, and the joint angles of 17 upper-limb items (excluding fingers) and 23 FMA upper-limb items (excluding reflexes and fingers) were measured. From the measurement results, we analyzed the time-series data of each movement and obtained the correlation between the joint angles of each part. Discriminant analysis showed that 17 and 6 items had a concordance rate of ≥80% (80.0~95.6%) and <80% (64.4~75.6%), respectively. In the multiple regression analysis of continuous variables of FMA, a good regression model was obtained to predict the FMA with three to five joint angles. The discriminant analysis for 17 evaluation items suggests the possibility of roughly calculating FMA scores from joint angles.

[Long-Term Survival with Multidisciplinary Treatment and Nutritional Therapy for Thoracic Esophageal Cancer with Multiple Liver Metastases-A Case Report].

The patient was a 63-year-old man with a chief complaint. Upper endoscopic examination revealed a semicircular type 2 lesion, sized 24-28 cm, on the incisor teeth and a 3 cm sized elevated lesion directly above the EGJ. When biopsy was performed, squamous cell carcinoma(SCC)was detected. In this case, lymph node metastasis and multiple liver metastases were observed, and diagnosis at the first examination was cT3N2M1(HEP), Stage Ⅳ. After 7 months of chemotherapy, he underwent right thoracic esophageal subtotal resection, 3-field lymph node dissection, posterior mediastinal gastric tube reconstruction, and partial hepatectomy. Despite receiving postoperative chemotherapy, he showed recurrence in the liver(S8). Four additional courses of chemotherapy were administered and partial hepatectomy(S8)was performed, without the appearance of new lesions. He was considered to be cured 1 year and 6months after starting the treatment and was followed- up without chemotherapy. However, 4 months later, chemotherapy was resumed when right adrenal and abdominal wall metastases and liver recurrence(S3)were found. After that, the regimen was modified, and he continued treatment. More than 4 years have passed since the start of treatment, but the treatment has been continued without a decline in ADL.

Genomic Landscape of Esophageal Squamous Cell Carcinoma in a Japanese Population.

BACKGROUND & AIMS: Esophageal squamous cell carcinoma (ESCC) is the predominant form of esophageal cancer in Japan. Smoking and drinking alcohol are environmental risk factors for ESCC, whereas single nucleotide polymorphisms in ADH1B and ALDH2, which increase harmful intermediates produced by drinking alcohol, are genetic risk factors. We conducted a large-scale genomic analysis of ESCCs from patients in Japan to determine the mutational landscape of this cancer. METHODS: We performed whole-exome sequence analysis of tumor and nontumor esophageal tissues collected from 144 patients with ESCC who underwent surgery at 5 hospitals in Japan. We also performed single-nucleotide polymorphism array-based copy number profile and germline genotype analyses of polymorphisms in ADH1B and ALDH2. Polymorphisms in CYP2A6, which increase harmful effects of smoking, were analyzed. Functions of TET2 mutants were evaluated in KYSE410 and HEK293FT cells. RESULTS: A high proportion of mutations in the 144 tumor samples were C to T substitution in CpG dinucleotides (called the CpG signature) and C to G/T substitutions with a flanking 5' thymine (called the APOBEC signature). Based on mutational signatures, patients were assigned to 3 groups, which associated with environmental (drinking and smoking) and genetic (polymorphisms in ALDH2 and CYP2A6) factors. Many tumors contained mutations in genes that regulate the cell cycle (TP53, CCND1, CDKN2A, FBXW7); epigenetic processes (MLL2, EP300, CREBBP, TET2); and the NOTCH (NOTCH1, NOTCH3), WNT (FAT1, YAP1, AJUBA) and receptor-tyrosine kinase-phosphoinositide 3-kinase signaling pathways (PIK3CA, EGFR, ERBB2). Mutations in EP300 and TET2 correlated with shorter survival times, and mutations in ZNF750 associated with an increased number of mutations of the APOBEC signature. Expression of mutant forms of TET2 did not increase cellular levels of 5-hydroxymethylcytosine in HEK293FT cells, whereas knockdown of TET2 increased the invasive activity of KYSE410 ESCC cells. Computational analyses associated the mutations in NFE2L2 we identified with transcriptional activation of its target genes. CONCLUSIONS: We associated environmental and genetic factors with base substitution patterns of somatic mutations and provide a registry of genes and pathways that are disrupted in ESCCs. These findings might be used to design specific treatments for patients with esophageal squamous cancers.

[Three-Year Survival after Lymphadenectomy for Residual Lymph Node Metastasis of Esophageal Cancer with Invasion into the Trachea and Carotid Artery after Chemoradiotherapy - A Case Report].

INTRODUCTION: Chemoradiotherapy(CRT)is an effective treatment method for esophageal cancer. In early stages, it is a standard therapy combined with surgery. However, CRT achieves definitive complete response(CR)in only about 20% of advanced cancer with invasion into adjacent organs. Then, surgery is the only treatment for curative therapy. We report a case of a patient with 3-year survival who underwent lymphadenectomy for residual cancer after CRT for advanced esophageal cancer with invasion into the trachea and right cervical artery. CASE DESCRIPTION: The patient was a 71-year-old woman. Various examinations revealed a cervical esophageal cancer, which had a right cervical lymph node metastasis with invasion into the trachea and right common cervical artery(cT4b[LYM-Tr, RCCA], N1, M0, cStage III C(UICC TNM classification). Induction chemotherapy(DCF; docetaxel[DTX]plus cisplatin[CDDP]plus 5-fluorouracil[5-FU])was initiated, but neither the cancer primary site nor the lymph node metastasis decreased. Then, she received chemoradiotherapy(5-FU plus CDDP and 40.8 Gy). After that, endoscopic and pathological examination showed CR of the primary site, but CT still indicated the presence of a residual lesion in the lymph node. As we diagnosed the residual tumor as being close to the trachea and RCCA, but not infiltrating them, lymphadenectomy was performed, which was possible to preserve the trachea and RCCA. The postoperative histopathological report indicated lymph node metastasis in the right cervical lymph node with a negative radial margin. It has now been about 3 years since her operation, and she is alive and disease-free.

A Novel IgM-capture enzyme-linked immunosorbent assay using recombinant Vag8 fusion protein for the accurate and early diagnosis of Bordetella pertussis infection.

An ELISA that measures anti-PT IgG antibody has been used widely for the serodiagnosis of pertussis; however, the IgG-based ELISA is inadequate for patients during the acute phase of the disease because of the slow response of anti-PT IgG antibodies. To solve this problem, we developed a novel IgM-capture ELISA that measures serum anti-Bordetella pertussis Vag8 IgM levels for the accurate and early diagnosis of pertussis. First, we confirmed that Vag8 was highly expressed in all B. pertussis isolates tested (n = 30), but little or none in other Bordetella species, and that DTaP vaccines did not induce anti-Vag8 IgG antibodies in mice (i.e. the antibody level could be unaffected by the vaccination). To determine the immune response to Vag8 in B. pertussis infection, anti-Vag8 IgM levels were compared between 38 patients (acute phase of pertussis) and 29 healthy individuals using the anti-Vag8 IgM-capture ELISA. The results revealed that the anti-Vag8 IgM levels were significantly higher in the patients compared with the healthy individuals (P < 0.001). ROC analysis also showed that the anti-Vag8 IgM-capture ELISA has higher diagnostic accuracy (AUC, 0.92) than a commercial anti-PT IgG ELISA kit. Moreover, it was shown that anti-Vag8 IgM antibodies were induced earlier than anti-PT IgG antibodies on sequential patients' sera. These data indicate that our novel anti-Vag8 IgM-capture ELISA is a potentially useful tool for making the accurate and early diagnosis of B. pertussis infection.

Ultraviolet-C irradiation to titanium implants increases peri-implant bone formation without impeding mineralization in a rabbit femur model.

OBJECTIVES: Volume and bone quality of peri-implant supporting bone, in particular, at implant neck region, as well as bone-implant contact ratio, is important for long-term stability of implants. Ultraviolet-C (UVC) irradiation is known to enhance the osseointegration capability of titanium implants. However, the histological determination was performed only on a rat model, but not pre-clinical animal model such as a rabbit model. The purpose of this study was to determine the effects of UVC irradiation on titanium implants on the volume and mineral density of peri-implant supporting bone formation in a rabbit femur model. MATERIALS AND METHODS: Acid-etched pure titanium screw implants with or without 3 mW/cm2 UVC irradiation for 48 h were placed in rabbit femur diaphyses. Peri-implant bone tissue formation was analyzed at 3 and 8 weeks post-operatively by histology and micro-CT-based bone morphometry after calibration with hydroxyl apatite phantoms. RESULTS: UVC pre-irradiated implants accumulated a higher density of cells and thicker and longer bone tissue attachments that continued into the inner basic lamellae of the surface of existing cortical bone at 3 and 8 weeks than the implants without irradiation. Although the bone mineral density around both implants was equivalent to that of the existing cortical bone, bone volume was greater with UVC pre-irradiation in two-thirds or more of the apical region throughout the observation period. CONCLUSIONS: These results indicate that UVC treatment increased the volume of cortical-like bone tissue in the coronal region of titanium implants without deterioration of bone mineral density.

[A Case of Unresectable Local Recurrence of Gastric Cancer Successfully Resected after Pre-Operative Chemotherapy with Trastuzumab].

A 69-year-old man was diagnosed with advanced gastric cancer and underwent total gastrectomy (tubular adenocarcinoma, tub2, pT3N0M0, stageⅡA). Eight months after the surgery, recurrence on the anastomosis was observed. Tumor invasion of the aortic artery was suspected, and the patient was considered inoperable. He was treated with S-1/CDDP plus trastuzumab therapy as a neoadjuvant chemotherapy regimen. After 4 courses of the chemotherapy, significant tumor reduction was observed, and the patient underwent anastomosis resection. Chemotherapy with trastuzumab appears to be an effective NAC treatment for HER2-positive, advanced gastric cancer.

Structural basis for broad detection of genogroup II noroviruses by a monoclonal antibody that binds to a site occluded in the viral particle.

Human noroviruses are genetically and antigenically highly divergent. Monoclonal antibodies raised in mice against one kind of norovirus virus-like particle (VLP), however, were found to have broad recognition. In this study, we present the crystal structure of the antigen-binding fragment (Fab) for one of these broadly reactive monoclonal antibodies, 5B18, in complex with the capsid-protruding domain from a genogroup II genotype 10 (GII.10) norovirus at 3.3-Å resolution and, also, the cryo-electron microscopy structure of the GII.10 VLP at ∼10-Å resolution. The GII.10 VLP structure was more similar in overall architecture to the GV.1 murine norovirus virion than to the prototype GI.1 human norovirus VLP, with the GII.10 protruding domain raised ∼15 Å off the shell domain and rotated ∼40° relative to the GI.1 protruding domain. In the crystal structure, the 5B18 Fab bound to a highly conserved region of the protruding domain. Based on the VLP structure, this region is involved in interactions with other regions of the capsid and is buried in the virus particle. Despite the occluded nature of the recognized epitope in the VLP structure, enzyme-linked immunosorbent assay (ELISA) binding suggested that the 5B18 antibody was able to capture intact VLPs. Together, the results provide evidence that the norovirus particle is capable of extreme conformational flexibility, which may allow for antibody recognition of conserved surfaces that would otherwise be buried on intact particles.

Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats.

Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolites profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the early time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an early event of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and early DILI preclinical biomarkers.

Complete sequencing and characterization of 21,243 full-length human cDNAs.

As a base for human transcriptome and functional genomics, we created the "full-length long Japan" (FLJ) collection of sequenced human cDNAs. We determined the entire sequence of 21,243 selected clones and found that 14,490 cDNAs (10,897 clusters) were unique to the FLJ collection. About half of them (5,416) seemed to be protein-coding. Of those, 1,999 clusters had not been predicted by computational methods. The distribution of GC content of nonpredicted cDNAs had a peak at approximately 58% compared with a peak at approximately 42%for predicted cDNAs. Thus, there seems to be a slight bias against GC-rich transcripts in current gene prediction procedures. The rest of the cDNAs unique to the FLJ collection (5,481) contained no obvious open reading frames (ORFs) and thus are candidate noncoding RNAs. About one-fourth of them (1,378) showed a clear pattern of splicing. The distribution of GC content of noncoding cDNAs was narrow and had a peak at approximately 42%, relatively low compared with that of protein-coding cDNAs.

[Complete response in a case of advanced esophageal cancer infiltrating into the main bronchus treated by chemoradiation therapy].

We report a case of advanced esophageal cancer infiltrating into the trachea that was treated by chemoradiation therapy. The patient was a 49-year-old man who complained of dysphagia and dyspnea. Various examinations revealed an esophageal cancer with direct invasion into the trachea( cT4b[ Tr], N2[ 106recR, 106recL, 106pre, 1], M0, cStage IIIc). He underwent radiotherapy. Simultaneously, he was administered morphine to relieve dyspnea and steroid to prevent tracheal edema. From the eight day of radiation therapy, chemotherapy was initiated( DCF; docetaxe[l DTX] +cisplatin[ CDDP] + 5-fluorouracil[ 5-FU]). This chemoradiation therapy considerably reduced the esophageal tumor size. Thereafter, the patient underwent 2 additional courses of chemotherapy( FAP; 5-FU+adriamycin[ ADM] +CDDP). The therapeutic effect was judged as complete response. The patient is still alive without recurrence for 3 years and 6 months after the first treatment. There are some reports about airway stenting and adjuvant therapy for airway obstruction caused by esophageal cancer. However, there are few reports on chemoradiotherapy for esophageal cancer invading into the trachea with administration of steroids to prevent tracheal edema. We believe that this is an effective treatment.

Specific ion effects on the aggregation of polysaccharide-based polyelectrolyte complex particles induced by monovalent ions within Hofmeister series.

Polysaccharide-based polyelectrolyte complex (PEC) particles have been utilized as carriers for drug delivery systems (DDS) and as building components for material development. Despite their versatility, the aggregation mechanism of PEC particles in the presence of salts remains unclear. To clarify the aggregation mechanism, the specific ion effects of monovalent salts within the Hofmeister series on the aggregation behavior of PEC particles composed of chitosan and chondroitin sulfate C, which are often used as DDS carriers and materials, were studied. Here, we found that weakly hydrated chaotropic anions promoted the aggregation of positively charged PEC particles. The hydrophobicity of the PEC particles was increased by these ions. Strongly hydrated ions such as Cl- are less likely to accumulate in these particles, whereas weakly hydrated chaotropic ions such as SCN- are more likely to accumulate. Molecular dynamics simulations suggested that the hydrophobicity of PECs might be strengthened by ions due to changes in intrinsic and extrinsic ion pairs and hydrophobic interactions. Based on our results, it is expected that the control of surface hydrophilicity or hydrophobicity is an effective approach for controlling the stability of PEC particles in the presence of ions.

Chronic heat stress induces renal fibrosis and mitochondrial dysfunction in laying hens.

BACKGROUND: Heat stress in laying hens negatively affects egg production and shell quality by disrupting the homeostasis of plasma calcium and phosphorus levels. Although the kidney plays an important role in calcium and phosphorus homeostasis, evidence regarding the effect of heat stress on renal injury in laying hens is yet to be elucidated. Therefore, the aim of this study was to evaluate the effects of chronic heat stress on renal damage in hens during laying periods. METHODS: A total of 16 white-leghorn laying hens (32 weeks old) were randomly assigned to two groups (n = 8). One group was exposed to chronic heat stress (33 °C for 4 weeks), whereas the other group was maintained at 24 °C. RESULTS: Chronic heat exposure significantly increased plasma creatinine and decreased plasma albumin levels (P < 0.05). Heat exposure also increased renal fibrosis and the transcription levels of fibrosis-related genes (COLA1A1, αSMA, and TGF-ß) in the kidney. These results suggest that renal failure and fibrosis were induced by chronic heat exposure in laying hens. In addition, chronic heat exposure decreased ATP levels and mitochondrial DNA copy number (mtDNA-CN) in renal tissue, suggesting that renal mitochondrial dysfunction occurs under conditions of heat stress. Damaged mitochondria leak mtDNAs into the cytosol and mtDNA leakage may activate the cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) signaling pathway. Our results showed that chronic heat exposure activated the cGAS-STING pathway as indicated by increased expression of MDA5, STING, IRF7, MAVS, and NF-κB levels. Furthermore, the expression of pro-inflammatory cytokines (IL-12) and chemokines (CCL4 and CCL20) was upregulated in heat-stressed hens. CONCLUSIONS: These results suggest that chronic heat exposure induces renal fibrosis and mitochondrial damage in laying hens. Mitochondrial damage by heat stress may activate the mtDNA-cGAS-STING signaling and cause subsequent inflammation, which contributes to the progression of renal fibrosis and dysfunction.

Analysis of the aggregation mechanism of chondroitin sulfate/chitosan particles and fabrication of hydrogel cell scaffolds.

In this study, the aggregation mechanism of polyion complex (PIC) particles from chitosan (CHI) and chondroitin sulfate C (CS) in phosphate-buffered saline (PBS) was analyzed, and a novel method for the fabrication of hydrogels via aggregation was developed. The PBS induced a decrease in the ζ-potential of the CS/CHI PIC particles, increase in their diameter, and aggregation in a concentration-dependent manner. The hydrogels prepared by mixing CS/CHI PIC particle dispersion and PBS showed the PIC components, with porous structure, high swelling ratio (161.4 ± 13.3%), and high storage moduli (26.2 ± 1.4 kPa). By mixing PBS with suspended adhesive cells and CS/CHI PIC particle dispersion, hydrogels with high cell-loading efficiency were successfully synthesized. The loaded cells within the hydrogels exhibited high viability, uniform distribution, and formation of cell aggregates. These results indicate that CS/CHI-based hydrogels have a potential application as three-dimensional scaffolds for cell culture in tissue engineering.

Surface modification of silica nonwoven fabrics for osteogenesis of bone marrow-derived mesenchymal stem cells.

Silica nonwoven fabrics (SNFs) with high mechanical strength and porosity are known to exhibit high cell proliferation and osteogenic differentiation potential of mesenchymal stem cells (MSCs) by morphologically mimicking the extracellular matrix (ECM). To further improve the osteoinductive ability of SNFs, it could be effective to increase the interaction between MSCs and ECM components because exogenous ECM components seem to modulate the fate of MSCs differentiation. In this study, we developed immobilization methods for ECM components, such as collagen, fibronectin, and chondroitin sulphate C on SNFs, to improve cell-matrix interactions and examined their suitability for bone tissue regeneration. Collagen and fibronectin were immobilized via physical adsorption and chondroitin sulphate C was also immobilized by the layer-by-layer method combined with chitosan on SNF surfaces to maintain the high porosity of SNFs. The treated SNFs were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. In osteogenic differentiation culture, modified SNFs showed significantly increased expression of osteogenic differentiation marker genes compared to unmodified SNFs. These results suggest that the present methods improve cell-matrix interactions and enhance the cellular functions of MSCs. We are convinced that these simple modification techniques for ECM components are effective in functionalizing various 3D fabric scaffolds possessing hydrophilic groups.

Effects of Dietary Brown Rice on the Growth Performance, Systemic Oxidative Status, and Splenic Inflammatory Responses of Broiler Chickens under Chronic Heat Stress.

The aim of this study was to evaluate the effects of dietary brown rice on the growth performance, systemic oxidative status, and splenic inflammatory responses of broiler chickens under both thermo-neutral and chronic heat stress conditions. Forty 12-day-old male broiler chickens (ROSS 308) were randomly assigned to two groups and fed either a control diet (corn-based) or a brown rice-based diet. After seven days (19 days old), both groups were randomly divided into two sub-groups (n=10), one of which was exposed to heat stress (33°C for 14 days), while the other was maintained at 24°C. Heat exposure reduced the body weight gain and feed intake (p<0.01) of both groups. In terms of oxidative plasma states, heat exposure reduced the glutathione peroxidase activity and increased the ceruloplasmin content, while the 2-thiobarbituric acid reactive substance and reduced glutathione levels were not affected adversely. Heat exposure activated the immune responses, as evidenced by increased plasma immunoglobin levels, and altered splenic immune-related gene expressions including heat shock proteins, toll-like receptor 4, and interleukin-12. Under both thermo-neutral and heat stress conditions, dietary brown rice improved the growth performance, decreased the immunoglobulin levels, and down-regulated the expression of splenic immune-related genes of broilers, although their systemic oxidative status was not affected. Dietary brown rice should be considered as a valuable component of broiler chicken feeds subjected to both thermo-neutral and heat stress conditions. The positive effects of brown rice on bird performance may be associated with the modulation of the immune responses, as reflected by the decreased production of immunoglobulins and altered splenic immune-related gene expression.

Fabrication and Characterization of Polysaccharide Composite Films from Polyion Complex Particles.

Biomaterials made of natural polysaccharides have attracted much attention due to the fact of their excellent properties, such as high biocompatibility and biodegradability, and their specific biological functions based on their chemical structures. This study demonstrates that polysaccharide composite films can be fabricated from polyion complexes (PICs) with their particles used as building components. Dispersion of PIC particles prepared by mixing, centrifugation, and re-dispersion of dilute solutions of cationic and anionic polysaccharides were cast, dried, and formed into films several micrometers thick. These films were homogenous and water insoluble. It was revealed that the component anionic polysaccharides affected the film's properties such as the swelling behavior and mechanical characteristics. Adhesion of NIH3T3 cells (integrin: high, CD44: lack or weak) and A549 cells (integrin: high, CD44: high) to the composite films were examined. Both NIH3T3 and A549 cells adhered to heparin/chitosan (HEP/CHI) film because HEP has an affinity for integrin through fibronectin. However, A549 cells adhered to chondroitin sulfate (CS)/CHI and hyaluronic acid (HYA)/CHI films, whereas NIH3T3 cells did not, because both CS and HYA have affinity for CD44. These results indicated that the biological functions of anionic polysaccharides were maintained on the surface of the composite films. It was also possible to fabricate films composed of three kinds of polysaccharides: one cationic polysaccharide and two kinds of anionic polysaccharides. These results show that the properties of films composed of three kinds of polysaccharides may be controllable depending on the anionic polysaccharide composition rates.

Overexpression of tyrosine kinase B protein as a predictor for distant metastases and prognosis in gastric carcinoma.

OBJECTIVE: Tyrosine kinase B (TrkB) is associated with aggressive behavior and poor prognosis in various cancers. Here we examined the association between TrkB expression and distant metastases/prognosis in gastric carcinoma (GC). PATIENTS AND METHODS: We analyzed TrkB expression in 161 GC patients by immunohistochemistry and Western blot analysis. The correlation of TrkB mRNA and protein expression levels was examined in 10 patients by RT-PCR assay. RESULTS: TrkB expression was of level 1 in 97 (60.2%) and level 2 in 64 (39.8%) patients. Patients with level 2 expression had a significantly higher incidence of distant metastases (p < 0.0001), well-differentiated tumors (p < 0.005), deeper depth of invasion (p < 0.005) and poorer disease-free and overall survival (p < 0.0001 each) compared to patients with level 1. Multivariate analysis identified the level of TrkB expression as an independent prognostic factor for both disease-free and overall survival (p < 0.01 and p < 0.0001, respectively). Both lymph node metastasis (odds ratio = 10.7) and TrkB expression (odds ratio = 9.3) were independent predictors of distant metastases. CONCLUSION: A high level of TrkB expression was observed in well-differentiated GC subtypes and is a predictor for distant metastases and prognosis in GC.

[Clinical trials of neo-adjuvant chemotherapy for advanced gastric cancer with peritoneal dissemination].

Since 2000, we have introduced pre-operative chemotherapy including intra-peritoneal chemotherapy to patients with positive cytology and with no non-curative factors except peritoneum. Since 2006, we have started phase I trial with S-1 and intra-peritoneal chemotherapy with docetaxel to improve the efficacy and safety of the pre-operative regimen for advanced gastric cancer with peritoneal dissemination. The combination therapy with local and systemic chemotherapy is a promising regimen for gastric cancer with peritoneal dissemination.