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Persistent CXCR4 expression after preoperative chemoradiotherapy predicts early recurrence and poor prognosis in esophageal cancer

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World Journal of Gastroenterology 2006年第47期12卷 7585-7590页

作者： Kenji Koishi Reigetsu Yoshikawa Tohru Tsujimura Tomoko Hashimoto-Tamaoki Syoudou Kojima Hidenori Yanagi takehira yamamura Yoshinori Fujiwara Second Department of Surgery Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Second Department of Surgery Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Institute for Advanced Medical Sciences Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Second Department of Pathology Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Institute for Advanced Medical Sciences Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Department of Genetics Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan

AIM: To study the effect of CXC chemokine receptor-4 (CXCR4) expression on disease progression and prognosis in esophageal cancer. METHODS: CXCR4 expression was evaluated in 37 patients with histologically confirmed esophageal squamous carcinomas (ESCC) undergoing preoperative chemoradiotherapy (CRT) by immunohistochemical staining. RESULTS: Eleven out of 37 ESCC patients showed a pathological complete response (CR) after CRT. CXCR4 protein expression was observed in cell cytoplasms of 13 tumors, and null expression was seen in 13 tumors. Distant recurrence was significantly more common in patients with positive CXCR4 expression (P = 0.0318). After a median follow-up time of 31.6 mo, 19 patients progressed (12 of 19 expressed positive CXCR4) and 11 died (10 of 11 expressed positive CXCR4). Overall survival was significantly correlated with lymph node metastasis (952.1 ± 53.8 d in negative group vs 475.1 ± 56.2 d in positive group, P = 0.023), distant metastasis (874.0 ± 60.4 d in negative group vs 434.9 ± 75.2 d in positive group, P = 0.014) and CRT (811.5 ± 51.2 d in responder group vs 459.6 ± 94.0 d in non-responder group, P = 0.00038) and further with an absence ofCXCR4 expression or no residual tumor (959.8 ± 51.0 d in null expression or no tumor group vs 412.0 ± 57.1 d in positive expression group, P = 0.0001). CONCLUSION: Persistent positive CXCR4 expression is implicated in tumor aggressiveness and poor prognosis in ESCC after CRT, and preoperative CRT may improve the prognosis of ESCC via CXCL12-CXCR4 signaling pathway.

关键词： CXC chemokine receptor-4 Metastasis Chemoradiotherapy Esophageal cancer

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Cyclooxygenase-2 expression after preoperative chemoradiotherapy correlates with more frequent esophageal cancer recurrence

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World Journal of Gastroenterology 2007年第16期13卷 2283-2288页

作者： Reigetsu Yoshikawa Yoshinori Fujiwara Kenji Koishi Syoudou Kojima Tomohiro Matsumoto Hidenori Yanagi takehira yamamura Tomoko Hashimoto-Tamaoki Takashi Nishigami Tohru Tsujimura Second Department of Surgery Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Institute for Advanced Medical Sciences Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Second Department of Surgery Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Institute for Advanced Medical Sciences Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Department of Genetics Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Second Department of Pathology Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan

AIM： To investigate the relationship between cycloo- xygenase-2 （COX-2）, and vascular endothelial growth factor （VEGF）, and to determine the clinical significance of this relationship in esophageal cancer patients undergoing chemoradiotherapy （CRT）. METHODS： Immunohistochemical staining was used to evaluate COX-2 and VEGF expression in 40 patients with histologically-confirmed esophageal squamous carcinoma （ESCC） who were undergoing preoperative CRT. RESULTS： Fourteen out of 40 ESCC patients showed a pathological complete response （CR） after CRT. COX-2 and VEGF protein expressions were observed in the cytoplasm of 17 and 13 tumors, respectively, with null expression in 9 and 13 tumors, respectively. COX-2 expression was strongly correlated with VEGF expression （P 〈 0.05）. There were also significant associations between COX-2 expression, tumor recurrence, and lymph-node involvement （P = 0.0277 and P = 0.0095, respectively）. COX-2 expression and VEGF expression had significant prognostic value for disease-free survival （log-rank test; P = 0.0073 and P = 0.0341, respectively）, but not for overall survival, as assessed by univariate analysis. expression correlates with VEGF expression and might be a useful prognostic factor for more frequent tumor recurrence in ESCC patients undergoing neoadjuvant CRT. These findings support the use of anti-angiogenic COX-2 inhibitors in the treatment of ESCC.

关键词： Chemoradiotherapy Cyclooxygenase-2 Esophageal cancer Metastasis Vascular endothelial growth factor

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Diffuse gastroduodenitis and pouchitis associated with ulcerative colitis

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World Journal of Gastroenterology 2006年第36期12卷 5913-5915页

作者： Hiroki Ikeuchi Kazutoshi Hori Takashi Nishigami Hiroki Nakano Motoi Uchino Mitsuhiro Nakamura Nobuaki Kaibe Masafumi Noda Hidenori Yanagi takehira yamamura Second Department of Surgery Hyogo College of Medicine Hyogo Japan Department of Gastroenterology Hyogo College of Medicine. Hyogo Japan Second Department of Pathology Hyogo College of Medicine. Hyogo Japan

We experienced a very rare case of ulcerative colitis (UC) accompanied with analogous lesions in the stomach, duodenum, and ileal J -pouch. Ileal J-pouch anal anastomosis was performed on a 29-year old woman in 1996. Six years later, she was admitted again to our hospital because of epigastralgia, nausea, watery diarrhea and low fever. Based on the results of endoscopic examination, we diagnosed it as pouchitis. Moreover, on hypotonic duodenography, expansion of the duodenal bulb and the descending portion were poor. Kerckring folds disappeared with typical lead-pipe appearance. The pathogenesis of the gastric and duodenal lesion in this patient was similar to that of the colonic lesions of UC. For the gastroduodenal lesions in this patient, symptomatic remission was obtained following administration of crushed mesalazine tablets (1500 mg/d) for 14 d with continuous administration of omeprazole. Firstly we used ciprofloxacin to treat pouchitis. On the fifth day, she got a fever because of catheter infection. In the catheter culture, methicillin-resistant Staphylococcus aureus (MRSA) was detected. Therefore we changed ciprofloxacin to vancomycin hydrochloride (Vancomycin?). Vancomycin was very effective, and the stool frequency dramatically improved in three days. Now she continues to take mesalazine, but her condition is stable and there has been no recurrence of pouchitis.

关键词： Ulcerative colitis Pouchitis Gastroduodenal lesions

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ECA39 is a novel distant metastasis-related biomarker in colorectal cancer

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World Journal of Gastroenterology 2006年第36期12卷 5884-5889页

作者： Reigetsu Yoshikawa Hidenori Yanagi Chun-Shen Shen Yoshinori Fujiwara Masafumi Noda Toshihiko Yagyu Makoto Gega Tsutomu Oshima takehira yamamura Haruki Okamura Yoshiro Nakano Tomonori Morinaga Tomoko Hashimoto-Tamaoki Second Department of Surgery Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Institute for Advanced Medical Sciences Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Department of Dermatology Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Department of Genetics Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan

AIM: To investigate the possible role of polysaccharide-K (PSK) -related markers in predicting distant metastasis and in the clinical outcome of colorectal cancer (CRC).METHODS: Firstly, we used protein microarrays to analyze the in vitro expression profiles of potential PSK-related markers in the human colorectal adenocarcinoma cell line SW480, which carries a mutant p53 gene. Then, we investigated the clinical implications of these markers in the prognosis of CRC patients. RESULTS: ECA39, a direct target of c-Myc, was identi-fied as a candidate protein affected by the anti-metastat-ic effects of PSK. Immunohistochemistry revealed that ECA39 was expressed at significantly higher levels in tumor tissues with distant metastases compared to those without (P < 0.00001). Positive ECA39 expression was shown to be highly reliable for the prediction of distant metastases (sensitivity: 86.7%, specificity: 90%, posi-tive predictive value: 86.7%, negative predictive value: 90%). A significantly higher cumulative 5-yr disease free survival rate was observed in the ECA39-negative patient group (77.3%) compared with the ECA39-positive patient group (25.8%) (P < 0.05). CONCLUSION: Our results suggest that ECA39 is a dominant predictive factor for distant metastasis in pa-tients with advanced CRC and that its suppression by PSK might represent a useful application of immuno-therapy as part of a program of integrated medicine.

关键词： ECA39 Distant metastasis Colorectal cancer Polysaccharide-K Integrated medicine

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Japanese Community Pharmacists’ Barriers to Conducting or Participating in Practice Research

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Pharmacology & Pharmacy 2015年第9期6卷 421-427页

作者： Yasuhiro Sawada Rieko takehira Shigeo yamamura Faculty of Pharmaceutical Sciences Josai International University Chiba Japan Welcia Yakkyoku Co. Ltd. Tokyo Japan

Objectives: This study identified barriers to Japanese community pharmacists’ active conduct or participation in practice research. Methods: Community pharmacists (n = 478) who gave presentations at three major pharmacy-related conferences in 2012 and 2013 were questioned about their difficulties of giving presentations, support for better presentations, and barriers to conducting pharmacy practice research in their practical setting. A questionnaire was mailed to and returned by the pharmacists directly. Results: We obtained 230 responses (47.9%). Presentation difficulties included pharmacists’ time constraints and lack of experience organizing the report’s results or discussion. Many thought statistical analysis support was necessary. The barriers were in sufficient time, community pharmacies’ lack of research supervisors, and other community pharmacists’ lack of understanding practice research’s importance. These were comparable to pharmacists’ barriers in other countries, except for money and funds. Conclusions: Japanese community pharmacists should clarify that practice research in their professional roles improves patients’ outcomes. Barriers were similar to pharmacists in other countries. Publication of pharmacists’ practice research results is important to expand their roles. Collaboration between faculties and pharmacists is a challenge for practice research development in the Japanese community setting.

关键词： Pharmacy Practice Research Barrier Community Pharmacist in Japan

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Japanese Community Pharmacists’ Practice Research Literacy

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Pharmacology & Pharmacy 2015年第9期6卷 436-441页

作者： Yasuhiro Sawada Rieko takehira Shigeo yamamura Faculty of Pharmaceutical Sciences Josai International University Chiba Japan Welcia Yakkyoku Co. Ltd. Tokyo Japan

Objectives: Lack of basic practice research literacy could be considered a barrier to conducting or participating in practice research. Therefore, we examined pharmacy practice research literacy in Japanese community pharmacists. Methods: Community pharmacists (n = 478) who delivered presentations at three major pharmacy-related conferences in 2012 and 2013 completed the survey. We selected 10 key terms related to practice research and asked participants whether they knew the meaning of. Questionnaires were sent to and returned by pharmacists via mail. Results: Of the 478 pharmacists who received questionnaires, 230 (47.9%) completed the survey. The response rates indicating that participants were familiar with the 10 key terms were approximately 50% or lower. The highest response rate was 67.0% for “bias”, and the lowest was 17.0% for “PICO/PECO: Patient-Intervention-Comparison-Outcome/Patient-Exposure-Comparison-Outcome”. Younger pharmacists tended to know several key terms, such as “p values”, “bias”, and “outcome”. Conclusion: Japanese community pharmacists were not knowledgeable with respect to conducting and participating in pharmacy practice research. Practice research knowledge was superior in younger pharmacists. Education in pharmacy schools and continuing professional development programs is important for community pharmacists’ practice research development.

关键词： Pharmacy Practice Research Research Literacy Japanese Community Pharmacists

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A Structural Equation Model (SEM) for Pharmacist Competencies in Improving Quality of Life of Cancer Patients: Effect of Missing Values on the SEM

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Pharmacology & Pharmacy 2011年第3期2卷 226-232页

作者： Rieko takehira Keiko Murakami Sirou Katayama Kenji Nishizawa Shigeo yamamura Faculty of Pharmaceutical Sciences Josai International University Department of Pharmacy Nippon Medical University Hospital

Objective: With the goal of improving health-related quality of life (HRQOL) in cancer patients, we previously reported a structural equation model (SEM) of subjected QOL and qualifications of pharmacists, based on a series of questionnaires completed by patients and pharmacists. However, several patients and pharmacists were excluded from the previous study because it was not always possible to obtain all the data intended for collection. In order to reveal the effect of missing data on the SEM, we established SEMs of HRQOL and the competency of pharmacists, using correlation matrices derived by two different statistical methods for handling missing data. Method: Fifteen cancer patients hospitalized for cancer and were receiving opioid analgesics for pain control, and eight pharmacists were enrolled in this study. Each subject was asked four times weekly to answer questions presented in a questionnaire. SEMs were explored using two correlation matrices derived with pair-wise deletion (PD matrix) and list-wise deletion (LD matrix). The final models were statistically evaluated with certain goodness-of-fit criteria. Results: Data were intended to be collected four times weekly for each patient, but there were some missing values. The same SEMs for HRQOL were optimized using both the LD and PD matrices. Although the path diagrams of the SEMs were not identical in the “competency of pharmacists,” the two models suggested that a higher competency of a pharmacist lowered the “severity” of condition and increased the “comfort” of patients, resulting in an increase in the subjected QOL. Conclusion: In collecting data for clinical research, missing values are unavoidable. When the structure of the model was robust enough, the missing data had a minor effect on our SEM of QOL. In QOL research, the LD matrix as well as the PD matrix would be effective, provided the model is sufficiently robust.

关键词： QOL Cancer Patients Structural Equation Model Pharmacists Missing Data

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A Structural Equation Model (SEM) for Pharmacist Competencies in Improving Quality of Life of Cancer Patients: Effect of Missing Values on the SEM

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Pharmacology ＆ Pharmacy 2011年第3期

作者： Rieko takehira Keiko Murakami Sirou Katayama Kenji Nishizawa Shigeo yamamura

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