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Search Results: 1 - 10 of 1027 matches for " Keishi Yamashita "
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Newly emerging standard chemotherapies for gastric cancer and clinical potential in elderly patients
Shinichi Sakuramoto,Keishi Yamashita,Masahiko Watanabe
World Journal of Gastrointestinal Oncology , 2009,
Abstract: With the increase in average life expectancy, the rate of occurrence of gastric cancer in elderly patients is also rising. While many clinical trials have been conducted to examine the effect of chemotherapy treatment on gastric cancer, age limits for eligible subjects have prevented the establishment of standards for chemotherapy in elderly patients with gastric cancer. As of March 2009, evidence-based standard chemotherapy regimens were established. In the Western world, debates centered on the ECF (Epirubicin/cisplatin/5-FU) or DCF (Docetaxel/cisplatin/5-FU) regimens based on the phase III randomized controlled trial at the Royal Marsden Hospital (RMH) or the V325 study, respectively. The JCOG9912 and SPIRITS trials emerged from Japan indicating attractive regimens that include S-1 for advanced gastric cancer patients. Using these active anticancer drugs, the trials that studied the efficacy of adjuvant therapies or surgical approaches, such as the Int-116/MAGIC/ACTS-GC trials, have actually succeeded in demonstrating the benefits of adjuvant therapies in gastric cancer patients. For cases of gastric cancer in elderly patients, treatment policies should consider these studies while analyzing not only the therapeutic effects but also drug toxicity, individual general health conditions, and social factors to select treatments that emphasize quality of life.
The Homeobox Only Protein Homeobox (HOPX) and Colorectal Cancer
Keishi Yamashita,Hiroshi Katoh,Masahiko Watanabe
International Journal of Molecular Sciences , 2013, DOI: 10.3390/ijms141223231
Abstract: The HOP (homeobox only protein) homeobox (HOPX) is most closely related to the homeobox protein that contains a homeobox-like domain but lacks certain conserved residues required for DNA binding. Here, we review the current understanding of HOPX in the progression of colorectal cancer (CRC). HOPX was initially reported as a differentiation marker and is expressed in various normal tissues. In the colon, HOPX is expressed uniquely in the quiescent stem cell, +4, and in differentiated mucosal cells of the colon. HOPX expression is markedly suppressed in a subset of cancers, mainly in an epigenetic manner. CRC may include separate entities which are differentially characterized by HOPX expression from a prognostic point of view. HOPX itself can regulate epigenetics, and defective expression of HOPX can result in loss of tumor suppressive function and differentiation phenotype. These findings indicate that HOPX may be both a central regulator of epigenetic dynamics and a critical determinant for differentiation in human cells. HOPX downstream targets were identified in CRC cell lines and hold promise as candidates for therapeutic targets of CRC, such as EphA2 or AP-1. Further analysis will elucidate and confirm the precise role of such proteins in CRC progression.
Trend in gastric cancer: 35 years of surgical experience in Japan
Keishi Yamashita,Shinichi Sakuramoto,Masayuki Nemoto,Tomotaka Shibata
World Journal of Gastroenterology , 2011, DOI: 10.3748/wjg.v17.i29.3390
Abstract: AIM: To investigate the trend in gastric cancer surgery in the context of rapid therapeutic advancement in Japan and East Asia. METHODS: A retrospective analysis was performed on 4163 patients who underwent gastric resection for gastric cancer with histological confirmation between 1971 and 2007 at the surgical unit in Kitasato University Hospital, to determine the trend in gastric cancer requiring surgery. RESULTS: Gastric cancer requiring surgical resection increased in our hospital, but the incidence adjusted for population was constant during the observed period. Interestingly, the ratio of diffuse type/intestinal type gastric cancer was unexpectedly unchanged, and that of advanced/early gastric cancer (EGC) was, however, markedly reduced, while the actual incidence of potentially curative advanced gastric cancer tended to decrease. The incidence of EGC requiring surgery tended to increase as a whole, which is consistent with increased prevalence of endoscopic surveillance. As a result, overall survival and mortality of gastric cancer requiring gastric resection has recently markedly improved. CONCLUSION: In Japan, planned interventions may improve surgical gastric cancer mortality, but an unexpected trend of persistent existence of intestinal type cancer suggests the need for more robust medical intervention.
Cancer specific promoter CpG Islands hypermethylation of HOP homeobox (HOPX) gene and its potential tumor suppressive role in pancreatic carcinogenesis
Waraya Mina,Yamashita Keishi,Katoh Hiroshi,Ooki Akira
BMC Cancer , 2012, DOI: 10.1186/1471-2407-12-397
Abstract: Background We have recently identified HOP hoemobox (HOPX) as a tumor suppressor gene candidate, characterized by tumor-specific promoter DNA hypermethylation in human cancers, and it can remarkably inhibit tumors’ aggressive phenotypes. In this current study, we for the first time examined methylation level of HOPX and tested the functional relevance in pancreatic cancer (PC). Methods Clinical features of HOPX promoter hypermethylation was investigated in 89 PC tissues, and immunohistochemistry was added. We also examined its functional relevance in phenotype assays such as soft agar, proliferation, invasion, and cell cycle analysis. Results PC tissues had HOPX gene hypermethylation as compared to the corresponding normal pancreas tissues, and its uniqueness was robust to discriminate tumor from normal tissues (AUC = 0.85, P < 0.0001). Unexpectedly, HOPX was increased in expression in tumor tissues, and immunohistochemistry revealed its predominant expression in the Langerhans islet cells, where HOPX was reduced in expression for PC cells with promoter hypermethylation. HOPX transfectants exhibited G1 arrest with subG1 accumulation, and inhibited tumor forming and invasive ability. Conclusion Defective expression of HOPX which is consistent with promoter DNA hypermethylation may explain aggressive phenotype of pancreatic cancer, and intense expression of HOPX in the Langerhans cells may in turn uniquely contribute to pancreatic carcinogenesis.
Therapeutic potential of PRL-3 targeting and clinical significance of PRL-3 genomic amplification in gastric cancer
Akira Ooki, Keishi Yamashita, Shiro Kikuchi, Shinichi Sakuramoto, Natsuya Katada, Mina Waraya, Hiroshi Kawamata, Hiroshi Nishimiya, Kazunori Nakamura, Masahiko Watanabe
BMC Cancer , 2011, DOI: 10.1186/1471-2407-11-122
Abstract: PRL-3 genomic amplification was analyzed using quantitative-polymerase chain reaction and/or fluorescence in situ hybridization in 77 primary gastric tumors. The anticancer activity of PRL-3 inhibitor (1-4-bromo-2-benzylidene rhodanine) treatment was evaluated against cancer cells with different genetic and expression status.PRL-3 genomic amplification was closely concordant with high level of its protein expression in cell lines, and was found in 20% (8/40) among human primary tumors with its expression, which were all stage III/IV disease (40%, 8/20), but in none (0/37) among those without expression. Additionally, PRL-3 genomic amplification was associated with metastatic lymph node status, leading to advanced stage and thereby poor outcomes in patients with lymph node metastasis (P = 0.021). PRL-3 small interfering RNA robustly repressed metastatic properties, including cell proliferation, invasion, and anchorage-independent colony formation. Although neither PRL-3 genomic amplification nor expression level was responsible for the sensitivity to PRL-3 inhibitor treatment, the inhibitor showed dose-dependent anticancer efficacy, and remarkably induced apoptosis on all the tested cell lines with PRL-3 expression.We have for the first time, demonstrated that PRL-3 genomic amplification is one of the predominant mechanisms inducing its expression, especially in more advanced stage, and that PRL-3-targeted therapy may have a great potential against gastric cancer with its expression.Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related death worldwide [1]. Recent improvements in diagnostic tools and methods have facilitated detection of early GC and thereby excellent long-term survival. However, patients with advanced disease at the time of diagnosis remain poor outcomes. Metastasis is a multistep process, involving local invasion, dissemination, and re-establishment into distant organs, and is the major determinant of th
Associations between proinflammatory cytokines in the synovial fluid and radiographic grading and pain-related scores in 47 consecutive patients with osteoarthritis of the knee
Sumihisa Orita, Takana Koshi, Takeshi Mitsuka, Masayuki Miyagi, Gen Inoue, Gen Arai, Tetsuhiro Ishikawa, Eiji Hanaoka, Keishi Yamashita, Masaomi Yamashita, Yawara Eguchi, Tomoaki Toyone, Kazuhisa Takahashi, Seiji Ohtori
BMC Musculoskeletal Disorders , 2011, DOI: 10.1186/1471-2474-12-144
Abstract: Synovial fluid was harvested from the knees of 47 consecutive OA patients, and the levels of TNFα, IL-6, and NGF were measured using enzyme-linked immunosorbent assays. Osteoarthritic knees were classified using Kellgren-Lawrence (KL) grading (1-4). The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) was used to assess self-reported physical function, pain, and stiffness.TNFα and IL-6 were detectable in knee synovial, whereas NGF was not. TNFα was not correlated with the KL grade, whereas IL-6 had a significantly negative correlation. We observed differences in the correlations between TNFα and IL-6 with WOMAC scores and their subscales (pain, stiffness, and physical function). TNFα exhibited a significant correlation with the total score and its 3 subscales, whereas IL-6 exhibited a moderately significant negative correlation only with the subscale of stiffness.The present study demonstrated that the concentrations of proinflammatory cytokines are correlated with KL grades and WOMAC scores in patients with knee OA. Although TNFα did not have a significant correlation with the radiographic grading, it was significantly associated with the WOMAC score. IL-6 had a significant negative correlation with the KL grading, whereas it had only a weakly significant correlation with the subscore of stiffness. The results suggest that these cytokines play a role in the pathogenesis of synovitis in osteoarthritic knees in different ways: TNFα is correlated with pain, whereas IL-6 is correlated with joint function.Knee osteoarthritis (OA) is a common chronic degenerative disease characterized by the loss of articular cartilage components due to an imbalance between extracellular matrix destruction and repair [1]. The entire joint structure is affected, including the synovial membrane and subchondral bone, and OA can be recognized as an irregularity and deformity of joint spaces in radiographic images. Its main clinical sign is joint pain, which not only contr
Neurofilament Heavy Polypeptide Regulates the Akt-β-Catenin Pathway in Human Esophageal Squamous Cell Carcinoma
Myoung Sook Kim,Xiaofei Chang,Cynthia LeBron,Jatin K. Nagpal,Juna Lee,Yiping Huang,Keishi Yamashita,Barry Trink,Edward A. Ratovitski,David Sidransky
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0009003
Abstract: Aerobic glycolysis and mitochondrial dysfunction are common features of aggressive cancer growth. We observed promoter methylation and loss of expression in neurofilament heavy polypeptide (NEFH) in a significant proportion of primary esophageal squamous cell carcinoma (ESCC) samples that were of a high tumor grade and advanced stage. RNA interference-mediated knockdown of NEFH accelerated ESCC cell growth in culture and increased tumorigenicity in vivo, whereas forced expression of NEFH significantly inhibited cell growth and colony formation. Loss of NEFH caused up-regulation of pyruvate kinase-M2 type and down-regulation of pyruvate dehydrogenase, via activation of the Akt/β-catenin pathway, resulting in enhanced aerobic glycolysis and mitochondrial dysfunction. The acceleration of glycolysis and mitochondrial dysfunction in NEFH-knockdown cells was suppressed in the absence of β-catenin expression, and was decreased by the treatment of 2-Deoxyglucose, a glycolytic inhibitor, or API-2, an Akt inhibitor. Loss of NEFH activates the Akt/β-catenin pathway and increases glycolysis and mitochondrial dysfunction. Cancer cells with methylated NEFH can be targeted for destruction with specific inhibitors of deregulated downstream pathways.
Cysteine Dioxygenase 1 Is a Tumor Suppressor Gene Silenced by Promoter Methylation in Multiple Human Cancers
Mariana Brait, Shizhang Ling, Jatin K. Nagpal, Xiaofei Chang, Hannah Lui Park, Juna Lee, Jun Okamura, Keishi Yamashita, David Sidransky, Myoung Sook Kim
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0044951
Abstract: The human cysteine dioxygenase 1 (CDO1) gene is a non-heme structured, iron-containing metalloenzyme involved in the conversion of cysteine to cysteine sulfinate, and plays a key role in taurine biosynthesis. In our search for novel methylated gene promoters, we have analyzed differential RNA expression profiles of colorectal cancer (CRC) cell lines with or without treatment of 5-aza-2′-deoxycytidine. Among the genes identified, the CDO1 promoter was found to be differentially methylated in primary CRC tissues with high frequency compared to normal colon tissues. In addition, a statistically significant difference in the frequency of CDO1 promoter methylation was observed between primary normal and tumor tissues derived from breast, esophagus, lung, bladder and stomach. Downregulation of CDO1 mRNA and protein levels were observed in cancer cell lines and tumors derived from these tissue types. Expression of CDO1 was tightly controlled by promoter methylation, suggesting that promoter methylation and silencing of CDO1 may be a common event in human carcinogenesis. Moreover, forced expression of full-length CDO1 in human cancer cells markedly decreased the tumor cell growth in an in vitro cell culture and/or an in vivo mouse model, whereas knockdown of CDO1 increased cell growth in culture. Our data implicate CDO1 as a novel tumor suppressor gene and a potentially valuable molecular marker for human cancer.
Recognition of Japanese Phonographic Kana (Hiragana) and Logographic Kanji Characters by Passive Finger Tracing  [PDF]
Hikari Yamashita
Psychology (PSYCH) , 2014, DOI: 10.4236/psych.2014.53032

The present study assessed the ability of normal Japanese adults to recognize kanji and hiragana characters through passive finger tracing without visual cues. We tested fifty-six right-handed Japanese university students using the left or right hand. Participants recognized approximately 50% of 44 kanji characters, regardless of the hand they used. The results are consistent with previous findings in Chinese speakers. In contrast, the average correct response to the 44 hiragana was almost 80%, again irrespective of hand. The results are discussed in terms of differential processing systems for Japanese writing and of differential cerebral hemispheric specializations.

Optimal Investment Strategy for Kinked Utility Maximization: Covered Call Option Strategy  [PDF]
Miwaka Yamashita
Journal of Mathematical Finance (JMF) , 2014, DOI: 10.4236/jmf.2014.42006

This paper describes optimal investment strategies for kinked utility functions. One example is a CRRA utility function with a kink at a maximum wealth, which leads a covered call “like” strategy and the other is a CRRA utility function with a kink at a minimum wealth, which leads a protective put “like” strategy. This paper introduces analytic mathematical solutions providing a mathematical explanation of a dual utility where Black-Sholes assumption is utilized in the solutions. The intuitive solutions are clear for cases of those kinked utilities but minute mathematical explanation is described. Also a numerical simulation is performed for a covered call like strategy case.

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