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Tsunamis have damaged bridges to various extents in the 2004 Indian Ocean Tsunami. This paper reports an experimental investigation of the effect of perforations in the girders and parapets on the horizontal tsunami loads. The results reveal that the maximum pressures impinging on the front face of the pier and deck are 4.5 and 3 times the hydrostatic pressure at 80mm nominal wave heights. The percentage of force reduction of the bridge deck with 10% perforated girders and 60% perforated parapets is found to be close to the percentage of perforation area in the deck. However, it is also noted that perforations in the bridge deck can substantially reduce the tsunami forces acting on it throughout the force time history. Thus, less damage to the bridge is anticipated for the bridge deck with perforations in girders and parapets.

Background: Before the androgen target therapy era, flutamide was widely used for castration-resistant prostate cancer in Japan. Enzalutamide is currently the recommended treatment; however, the efficacy and safety of enzalutamide and flutamide after combined androgen blockade therapy with bicalutamide, has not been compared., Methods: Patients with castration-resistant prostate cancer who received combined androgen blockade therapy with bicalutamide were randomly assigned to receive either enzalutamide or flutamide. The primary endpoint for efficacy was the 3-month prostate-specific antigen response rate. This trial is registered with ClinicalTrials.gov (NCT02346578) and the University hospital Medical Information Network (UMIN000016301)., Results: Overall, 103 patients were enrolled. The 3- (80.8% vs. 35.3%; p < 0.001) and 6-month (73.1% vs. 31.4%; p < 0.001) prostate-specific antigen response rates were higher in the enzalutamide than in the flutamide group. The 3-month disease progression rates (radiographic or prostate-specific antigen progression) were 6.4% and 38.8% in the enzalutamide and flutamide groups, respectively [hazard ratio (HR): 0.16; 95% confidence interval (CI): 0.05-0.47; p < 0.001]; the 6-month rates were 11.4% and 51.1%, respectively (HR 0.22; 95% CI 0.09-0.50; p < 0.001). Enzalutamide provided superior prostate-specific antigen progression-free survival compared with flutamide (HR 0.29; 95% CI 0.15-0.54; p < 0.001). Median time to prostate-specific antigen progression-free survival was not reached and was 6.6 months in the enzalutamide and flutamide groups, respectively., Conclusions: As an alternative anti-androgen therapy in patients with castration-resistant prostate cancer who fail bicalutamide-combined androgen blockade therapy, enzalutamide provides superior clinical outcomes compared with flutamide. Enzalutamide should be preferred over flutamide in these patients.

Purpose: The aim of our retrospective study was to determine the time to progression to castration-resistant prostate cancer (CRPC) in prostate cancer patients who undergo combined androgen blockade (CAB), as well as their prognoses., Materials and Methods: We examined the overall survival (OS) and disease-specific survival rates, as well as the time to CRPC development, in 387 patients who were treated with CAB for prostate cancer. The disease-specific survival rate and time to CRPC were stratified by prostate-specific antigen (PSA) levels, Gleason score (GS), and presence of metastasis at diagnosis. We designated high-risk patients as those satisfying at least two of the following three criteria: extent of disease of bone metastasis grade ≥2, presence of metastasis at diagnosis, and a GS ≥8., Results: The 10- and 15-year OS rates were 74.0% and 50.4%, respectively, while the corresponding disease-specific survival rates were both 86.8%. Metastasis at diagnosis was an independent prognostic factor for disease-specific survival. The median time to CRPC development was 140.7 months. A PSA level ≥20 ng/mL, a GS ≥8, and the presence of metastasis at diagnosis were independent predictors of a shorter time to CRPC development. The 10-year disease-specific survival rate in the high-risk group was significantly lower than that in the low-risk group (approximately 74% vs. 98%), and the time to CRPC development was significantly shorter (median: 20.5 months vs. not reached)., Conclusions: The time to CRPC development was shorter in high-risk prostate cancer patients with metastases. Such patients require alternative novel treatment modalities., Competing Interests: CONFLICTS OF INTEREST T. Iguchi and T. Nakatani have received research funding from Astellas Japan (Tokyo, Japan), Bayer Yakuhin. Ltd (Osaka, Japan). The remaining authors have declared no conflict of interest.

Background: The aim of our retrospective study was to evaluate the 5-year survival and time to castration resistant prostate cancer in patients with hormone sensitive prostate cancer treated with the gonadotropin releasing hormone antagonist, degarelix. Another aim was to evaluate the effects of changing the treatment from degarelix to a gonadotropin releasing hormone agonist after achieving stable disease control, on the clinical and oncological outcomes., Results: Our analysis was based on the data of 108 patients with prostate cancer who were treated with degarelix. Of these, the treatment was changed from degarelix to a gonadotropin releasing hormone agonist in 57 patients (changed group), and the treatment with degarelix was continued in the other 51 (continued group). The overall 5-year survival was statistically superior in the changed (96.6%) group than that in the continued (74.1%) group ( p  = 0.006). The 5-year cancer-specific survival was also superior in the changed (100%) group than that in the continued (84.6%) group ( p  = 0.027). The average time to castration resistant prostate cancer was comparable in both the changed (43.3 months) and continued (35.2 months) groups ( p  = 0.117). Lower serum levels of prostate specific antigen and alkaline phosphatase were maintained after changing the therapy from degarelix to a gonadotropin releasing hormone agonist., Conclusions: Degarelix is effective in the treatment of prostate cancer. Degarelix therapy can also be safely changed to a gonadotropin releasing hormone agonist without any adverse clinical or oncological effects., Competing Interests: Permission to access the database for a review of the medical records of these patients was obtained from the Local Research Ethics Committee at Osaka City University (approval number 4011).The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Oral and cutaneous tissues are the most frequent origin in canine squamous cell carcinoma (SSC). In SCC, changes in adhesion molecule expression and transition from epithelial to mesenchymal phenotype are thought to be important in development of invasive behavior of neoplastic cells at the leading front of the tumor. We therefore investigated histological invasive front grading and epithelial-mesenchymal transition (EMT) in both oral SCCs and cutaneous SCCs. EMT was assessed by evaluating immunohistochemical expression of E-cadherin, β-catenin, desmoglein, vimentin, and N-cadherin. Regardless of the anatomic location, invasive front grading resulted in higher histological grades than grading of the surface. Most oral SCCs were of significantly higher histologic grade than cutaneous SCCs ( P < .01). Expression of E-cadherin, β-catenin, and desmoglein was significantly lower in oral SCC compared with cutaneous SCC ( P < .01). A significant association was found between invasive front grading and loss of E-cadherin, β-catenin, and desmoglein ( P < .01). Also, vimentin-positive neoplastic cells had low immunoreactivity of these adhesion molecules, and a few of these neoplastic cells were positive for N-cadherin. These results suggest not only E-cadherin and β-catenin but also desmoglein as markers for predicting biological behavior of canine SCC. Depending on their primary sites, EMT correlates with biological behavior and therefore histological grade of canine SCC. We suggest that combining invasive front grading with assessment of immunohistochemical expression of E-cadherin, β-catenin, and desmoglein may allow more accurate prediction of biological behavior of canine SCCs.

We sought to investigate the long-term outcomes after radical prostatectomy (RP) and external-beam radiation therapy (EBRT) for the treatment of localized prostate cancer in Japanese patients. RP and radiation therapy are curative treatments for localized prostate cancer. However, there is controversy around which treatment is superior in Japanese patients. The aim of our retrospective study was to compare the long-term clinical outcomes of each treatment. We retrospectively evaluated the overall survival (OS), cancer-specific survival (CSS) and biochemical failure-free survival (BFS) for patients who had been diagnosed with localized prostate cancer and treated with RP (n = 248) or conventional 2D or 3D-CRT EBRT (n = 182) between 1995 and 2009. The median OS was superior in the RP group compared with that in EBRT group (P < 0.001), although CSS was comparable for both treatment groups; BFS was superior for the EBRT group compared with that for the RP group (P = 0.04). Univariate analysis identified a prostate-specific antigen count (PSA)of ≥20 vs <20 mg/ml, clinical T-stage of the tumor and Gleason score as predictors for CSS. However, multivariate analysis did not identify a factor for CSS. Subgroup analysis was also performed based on clinical T stage, PSA and Gleason score, but there was no difference in each subgroup between RP and EBRT. Both treatments provided satisfactory clinical outcomes in terms of disease control in localized prostate cancer., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Amyloid-producing odontogenic tumors (APOTs) of the facial skin were diagnosed in 3 domestic cats. The neoplasms had the histopathological characteristics of the odontogenic tumor. The neoplastic cells were present in irregular islands, strands, and sheets. The peripheral neoplastic cells of the islands and strands were arranged in a palisading fashion, while the central cells were polyhedral to stellate and randomly arranged. Multiple spherules of homogeneous eosinophilic material were closely apposed to the neoplastic epithelial cells. The spherules stained with Congo red and produced an apple green birefringence under polarization microscopy, indicative of amyloid. Immunohistochemically, amyloid materials of the neoplasms reacted with polyclonal antibodies for ameloblastin, amelogenin, and sheathlin antibodies. Neoplastic epithelial cells also reacted with antiameloblastin, amelogenin, and sheathlin antibodies, with varied intensity. The histopathological and immunohistochemical characteristics of dermal neoplasms of the 3 cats were analogous to those of APOTs reported in the dog and the cat.

Xyloglucan is a major hemicellulosic component in plant cell walls. Phytopathogenic fungi secrete cell wall-degrading enzymes on their infection to hosts, while the nature of the cell wall-lytic enzymes of such fungi are yet to be fully understood. Verticillium dahliae is a soil-borne fungus that causes vascular wilt diseases in a variety of commercially important crops worldwide. We purified two types of xyloglucanases, XEG12A and XEG74B, from the culture of naturally isolated Verticillium dahliae strain 2148. XEG12A showed a molecular size of 23 kDa with its maximal activity at pH 7.5. XEG12A specifically hydrolyzed xyloglucan with no activity on other β-glucans. XEG74B had a molecular size of 110 kDa with its optimum pH at 6.0. XEG74B primarily hydrolyzed xyloglucan, with a slight activity on β-1,3-1,4-glucan. Analysis of hydrolytic products of xyloglucanooligasaccharide (XXXGXXXG) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that the both enzymes cleaved β-1,4-glucosidic linkage at the position of unbranched chain, while XEG74B showed a little fluctuation with the cleavage site. Both enzymes did not hydrolyzed xyloglucanoheptasaccharide (XXXG) at all. N-Terminal and internal amino acid sequencing of the enzymes revealed that XEG12A and XEG74B belonged to Glycoside Hydrolase (GH) Families 12 and 74, respectively. Based on these results we concluded that V. dahliae XEG12A and XEG74B were xyloglucan-specific endo-β-1,4-glucanases (EC 3.2.1.151)., (2016 by The Japanese Society of Applied Glycoscience.)

We investigated the influence of sweet and umami (savory) tastants on the intestinal absorption of cephalexin (CEX), a substrate of peptide transporter 1 (PEPT1, SLC15A1) in rats. After oral administration of glucose or mannitol to rats, CEX was administered together with a second dose of glucose or mannitol. Western blot analysis indicated that expression of PEPT1 in rat jejunum membrane was decreased by glucose, compared to mannitol. Furthermore, the maximum plasma concentration (Cmax) of orally administered CEX was reduced by glucose compared to mannitol. The effect of glucose was diminished by nifedipine, a L-type Ca(2+) channel blocker. We also found that Cmax of orally administered CEX was reduced by treatment with L-glutamic acid, compared to D-glutamic acid. Thus, excessive intake of glucose and L-glutamic acid may impair oral absorption of PEPT1 substrates., (Copyright © 2016. Published by Elsevier Inc.)

Osteosarcoma (OS), the most common bone tumor, includes OS of the head (OSH) and appendicular OS (OSA). In dogs, it is classified into 6 histologic subtypes: osteoblastic, chondroblastic, fibroblastic, telangiectatic, giant cell, and poorly differentiated. This study investigated the significance of the histologic classification relevant to clinical outcome and the histologic and immunohistochemical relationships between pleomorphism and expression of cytoskeletal proteins in 60 cases each of OSH and OSA. Most neoplasms exhibited histologic diversity, and 64% of OS contained multiple subtypes. In addition to the above 6 subtypes, myxoid, round cell, and epithelioid subtypes were observed. Although the epithelioid subtypes were observed in only OSH, no significant difference in the frequency of other subtypes was observed. Also, no significant relevance was observed between the clinical outcome and histologic subtypes. Cytokeratin (CK) was expressed in both epithelioid and sarcomatoid tumor cells in various subtypes, and all CK-positive tumor cells also expressed vimentin. Vimentin and α-smooth muscle actin (SMA) were expressed in all subtypes. A few SMA-positive spindle-shaped tumor cells exhibited desmin expression. Glial fibrillary acidic protein-positive tumor cells were observed in many subtypes, and some of these cells showed neurofilament expression. Although OSH exhibited significantly stronger immunoreactivity for SMA than OSA, no significant difference in other cytoskeletal proteins was observed. Some tumor cells had cytoskeletal protein expression compatible with the corresponding histologic subtypes, such as CK in the epithelioid subtype and SMA in the fibroblastic subtype. Thus, canine skeletal OS is composed of pleomorphic and heterogenous tumor cells as is reflected in the diversity of histologic patterns and expression of cytoskeletal proteins., (© The Author(s) 2015.)

Acetoacetyl-CoA thiolase is an enzyme that catalyses both the CoA-dependent thiolytic cleavage of acetoacetyl-CoA and the reverse condensation reaction. In Dictyostelium discoideum, acetoacetyl-CoA thiolase (DdAcat) is encoded by a single acat gene. The aim of this study was to assess the localization of DdAcat and to determine the mechanism of its cellular localization. Subcellular localization of DdAcat was investigated using a fusion protein with GFP, and it was found to be localized to peroxisomes. The findings showed that the targeting signal of DdAcat to peroxisomes is a unique nonapeptide sequence (15RMYTTAKNL23) similar to the conserved peroxisomal targeting signal-2 (PTS-2). Cell fractionation experiments revealed that DdAcat also exists in the cytosol. Distribution to the cytosol was caused by translational initiation from the second Met codon at position 16. The first 18 N-terminal residues also exhibited function as a mitochondrial targeting signal (MTS). These results indicate that DdAcat is a dual-localizing enzyme that localizes to peroxisomes, mitochondria and the cytosol using both PTS-2 and MTS signals, which overlap each other near the N-terminus, and the alternative utilization of start codons.

Chordomas of the tip of the tail in 6 ferrets were examined using histopathological, histochemical and immunohistochemical procedures. Histopathologically, round neoplastic cells containing numerous cytoplasmic vacuoles of varying sizes, categorized as "physaliphorous cells", were observed in the amorphous eosinophilic or pale basophilic myxoid stroma. Physaliphorous cells were arranged in lobules and in a "chordoid" or "cobblestone" manner. The neoplasms were diagnosed as benign chordoma without local invasion and metastasis. Histochemically, the cytoplasm of small neoplastic cells was positive for periodic acid-Schiff stain and alcian blue (AB) pH 2.5 and pH 1.0 stains, but negative for hyaluronidase digestion-AB pH 2.5 stain. All neoplastic cells were strongly stained with colloidal ion, negative for high iron diamine AB pH 2.5 and toluidine blue pH 2.5 stains, and positive for Mayer's mucicarmine stain. Immunohistochemistry using antibodies directed against low-molecular-weight cytokeratins (CK18, CK19 and CK20), vimentin and mucin core protein (MUC5AC) revealed that neoplastic cells had both epithelial and mesenchymal elements. The expression of low-molecular-weight cytokeratins suggests that neoplastic cells acquired the properties of glandular epithelial cells and produced epithelial mucus. Furthermore, the expression of cytokeratins, vimentin, S100 protein, brachyury and epithelial membrane antigen indicates that the neoplasms were equivalent to the classic type of human chordoma. Therefore, immunohistochemistry using these antibodies can be useful for the characterization of ferret chordoma.

Objectives: To examine the difference in improvement of lower urinary tract symptoms between morning and evening dosing of α1 -blocker naftopidil., Methods: A total of 177 male patients with nocturia were included in the present study and randomized to morning or evening dosing of naftopidil. The International Prostate Symptom Score, quality of life index and nocturia quality of life index were compared between the two study groups at 12 weeks., Results: A total of 143 patients (morning group: n = 70, evening group: n = 73) were analyzed as a result of the dropout of 34 patients because of failure to give consent, adverse events and failure to attend. Nocturia, quality of life index and nocturia quality of life index at 12 weeks were significantly better in the evening group compared with the morning group. In a multivariate model, both the dosing time of naftopidil and the initial nocturia quality of life index were significantly associated with change in nocturia quality of life index., Conclusions: Evening dosing of naftopidil seems to be more effective in treating nocturia in male patients with lower urinary tract symptoms., (© 2014 The Japanese Urological Association.)

Infantile malignant osteopetrosis (IMO) is a rare and fatal autosomal recessive condition characterized by a generalized increased in bone density. Hematopoietic stem cell transplantation (HSCT) is the only effective and rational therapy with achieving long-term disease-free survival. However, complications with HSCT for IMO remain unclear. Here we describe a male infant with IMO, carrying two novel mutations in the T-cell immune regulator 1 (TCIRG1) gene. The TCIRG1 gene encodes the a3 subunit of vacuolar H(+)-ATPase that plays an essential role in the resorptive function of osteoclasts. Direct sequencing of all 20 exons of the TCIRG1 gene revealed a single nucleotide change in exon 11 (c1305 G > T), which causes the substitution of Asp (GAT) for Glu (GAG) at position 435, and a two-nucleotide deletion in exon 16 (c1952-1953 del CA), causing a frame-shift mutation. However, the functional consequence of each mutation remains to be determined. Allogeneic HSCT was performed in the patient at the age of nine months. Donor engraftment was achieved, and abnormal bone metabolism and extramedullary hematopoiesis were corrected. Graft-versus-host disease was mild (grade I). However, the patient died of complication of pulmonary arterial hypertension at seven months after the HSCT. Postmortem examination revealed prominent vascular wall thickening of the pulmonary artery and macrophage infiltration to alveoli. It should be noted that a patient with IMO has a risk for pulmonary arterial hypertension, and the evaluation of pulmonary arterial flow should be included in the assessment of each patient with IMO even after HSCT.

Dictyostelium discoideum has protein kinases AKT/PKBA and PKBR1 that belong to the AGC family of kinases. The protein kinase B-related kinase (PKBR1) has been studied with emphasis on its role in chemotaxis, but its roles in late development remained obscure. The pkbR1 null mutant stays in the first finger stage for about 16 h or longer. Only a few aggregates continue to the migrating slug stage; however, the slugs immediately go back probably to the previous first finger stage and stay there for approximately 37 h. Finally, the mutant fingers diversify into various multicellular bodies. The expression of the pkbR1 finger protein probably is required for development to the slug stage and to express ecmB, which is first observed in migrating slugs. The mutant also showed no ST-lacZ expression, which is of the earliest step in differentiation to one of the stalk cell subtypes. The pkbR1 null mutant forms a small number of aberrant fruiting bodies, but in the presence of 10% of wild-type amoebae the mutant preferentially forms viable spores, driving the wild type to form nonviable stalk cells. These results suggest that the mutant has defects in a system that changes the physiological dynamics in the prestalk cell region of a finger. We suggest that the arrest of its development is due to the loss of the second wave of expression of a protein kinase A catalytic subunit gene (pkaC) only in the prestalk region of the pkbR1 null mutant.

Acetoacetyl-CoA thiolase (AT) is an enzyme that catalyses the CoA-dependent thiolytic cleavage of acetoacetyl-CoA to yield 2 molecules of acetyl-CoA, or the reverse condensation reaction. A full-length cDNA clone pBSGT-3, which has homology to known thiolases, was isolated from Dictyostelium cDNA library. Expression of the protein encoded in pBSGT-3 in Escherichia coli, its thiolase enzyme activity, and the amino acid sequence homology search revealed that pBSGT-3 encodes an AT. The recombinant AT (r-thiolase) was expressed in an active form in an E. coli expression system, and purified to homogeneity by selective ammonium sulfate fractionation and two steps of column chromatography. The purified enzyme exhibited a specific activity of 4.70 mU/mg protein. Its N-terminal sequence was (NH₂)-Arg-Met-Tyr-Thr-Thr-Ala-Lys-Asn-Leu-Glu-, which corresponds to the sequence from positions 15 to 24 of the amino acid sequence deduced from pBSGT-3 clone. The r-thiolase in the inclusion body expressed highly in E. coli was the precursor form, which is slightly larger than the purified r-thiolase. When incubated with the cell-free extract of Dictyostelium cells, the precursor was converted to the same size to the purified r-thiolase, suggesting that the presequence at the N-terminus is removed by a Dictyostelium processing peptidase.

The amyloid of canine amyloid-producing odontogenic tumor (APOT) was evaluated biochemically and immunohistochemically. The N-terminal amino-acid sequence of purified amyloid protein from a canine APOT was strikingly similar to the sequence in both rat ameloblastin and porcine sheathlin. Immunohistochemically, the amyloid in APOT from 9 dogs was strongly reactive with anti-rat ameloblastin, anti-porcine sheathlin, and anti-canine APOT amyloid and weakly reactive with anti-porcine amelogenin but negative for antibodies to cytokeratins, vimentin, desmin, alpha-smooth muscle actin, amyloid A, glial fibrillary acidic protein, or S100 protein. The neoplastic epithelial cells of APOT were focally reactive with antibodies to ameloblastin, sheathlin, amelogenin, and canine APOT amyloid. The similarity in amino-acid sequence of the amyloid protein of canine APOT to that of enamel proteins, such as ameloblastin, sheathlin, and amelogenin, and the expression of these antigens in both APOT amyloid and in the neoplastic cells suggest that the amyloid of canine APOT is derived from enamel proteins secreted by ameloblasts.

We investigated the expression of the alpha subunit of the Dictyostelium mitochondrial processing peptidase (Ddalpha-MPP) during development. Ddalpha-MPP mRNA is expressed at the highest levels in vegetatively growing cells and during early development, and is markedly downregulated after 10 h of development. The Ddalpha-MPP protein is expressed as two forms, designated alpha-MPP(H) and alpha-MPP(L), throughout the Dictyostelium life cycle. The larger form, alpha-MPP(H), is cleaved to produce the functional alpha-MPP(L) form. We were not able to isolate mutants in which the alpha-mpp gene had been disrupted. Instead, an antisense transformant, alphaA2, expressing alpha-MPP at a lower level than the wild-type AX-3 was isolated to examine the function of the alpha-MPP protein. Development of the alphaA2 strain was normal until the slug formation stage, but the slug stage was prolonged to approximately 24 h. In this prolonged slug stage, only alpha-MPP(H) was present, and alpha-MPP(L) protein and MPP activity were not detected. After 28 h, alpha-MPP(L) and MPP activity reappeared, and normal fruiting bodies were formed after a delay of approximately 8 h compared with normal development. These results indicate that MPP activity is controlled by the processing of alpha-MPP(H) to alpha-MPP(L) during development in Dictyostelium.

We cloned and characterized a cDNA encoding the Dictyostelium discoideum beta subunit of mitochondrial processing peptidase (Ddbeta-MPP). Western blot analysis of the mitochondrial subfractions revealed that Ddbeta-MPP is located in the mitochondrial matrix and membrane, whereas Dd(alpha)-MPP, another subunit of DdMPP, is located only in the matrix. Although expression of Ddbeta-MPP mRNA is down-regulated during early development, the level of the Ddbeta-MPP protein is constant throughout the Dictyostelium life cycle. In a transformant expressing the antisense RNA of the beta-MPP gene, unexpectedly, the beta-MPP protein increased about 1.8-fold relative to the wild type, and its mRNA increased 4.5-fold. Expression of other mitochondrial proteins, alpha-MPP and Cox IV, was also induced. These results suggest that antisense RNA inhibition of the beta-MPP gene induces gene expression of mitochondrial proteins, presumably in a retrograde signaling manner. This is the pathway of the transfer of information from the mitochondria to the nucleus.

Advanced technology in molecular biology has provided us powerful tools for the diagnosis and treatment for cancer. We herein adopted a new methodology to identify a novel cancer/testis (CT) antigen with high frequency of expression in colorectal cancer as follows: (a) combining laser microdissection and cDNA microarray was used to analyze the gene expression profile of colorectal cancer cells; (b) genes overexpressed in testis and underexpressed in normal colon epithelium were analyzed using cDNA microarray; and (c) the gene expression profile of colorectal cancer cells was compared with that of normal testis. Using this methodology, we selected 38 candidates for CT antigen. Among these genes, we identified a novel CT antigen, serine/threonine kinase 31 (STK31), which was previously reported as a gene expressed in spermatogonia. Reverse transcription-PCR analysis showed that STK31 gene expression levels in cancer samples were significantly higher (P < 0.0001) than those in normal samples. The STK31 gene was frequently expressed not only in colorectal cancer but also in gastric and esophageal cancer. Moreover, STK31 peptide was able to elicit specific CTLs and induced CTLs lysed either peptide-loading or endogenously STK31-expressing target cells. These results showed that the new methodology in this study facilitated identification of CT antigens and that STK31 may be a candidate for cancer immunotherapy against gastrointestinal cancer.

Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-beta superfamily and bone morphogenetic protein (BMP) subfamily, plays a role in regulation of development and differentiation. Although some members of BMP subfamily have been reported to correlate with cancer, the significance of GDF11 has not been studied in a clinical oncology setting. The current study explored the clinicopathological significance of GDF11 expression in colorectal cancer. Quantitative real-time reverse transcription-PCR in colorectal cancer specimens obtained from 130 patients showed that GDF11 mRNA expression in cancer tissue was significantly higher than in normal tissue (p=0.001). Tumors were classified as high GDF11 expression (n=65) or low GDF11 expression (n=65). Patients whose tumors had high GDF11 expression showed a high frequency of lymph node metastasis (p=0.049) and had more cancer-related deaths (p=0.040). Furthermore, the patients with high GDF11 expression had significantly poorer overall survival than those with low expression (p=0.0334). Although multivariate analysis showed that GDF11 was not an independent prognostic factor, these findings suggest that GDF11 may be a novel diagnostic and prognostic biomarker in patients with colorectal cancer.