論文 - 長島　健悟

Study designs and statistical analyses for biomarker research

Gosho M, Nagashima K, Sato Y

Sensors 12 （ 7 ） 8966 - 8986 2012年06月

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A distinct regulatory role of Th17 cytokines IL-17A and IL-17F in chemokine secretion from lung microvascular endothelial cells

Fujie H, Niu K, Ohba M, Tomioka Y, Kitazawa H, Nagashima K, Ohrui T, Numasaki M

Inflammation （Inflammation）  35 （ 3 ） 1119 - 1131 2012年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  03603997

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Th17 cytokines IL-17A and IL-17F play a critical role in the activation and recruitment of neutrophils at airway inflammation mainly through the induction of CXC chemokines in the lungs. Vascular endothelial cells belong to the category of major CXC chemokine-producing cells. However, until now, the precise role of Th17 cytokines in CXC chemokine secretion in lung microvascular endothelial cells (LMVECs) has not been fully elucidated. In this study, we examined the biological effects of Th17 cytokines IL-17A and IL-17F on CXCL1, CXCL5, and CXCL8 release in LMVECs. Both IL-17 receptor A (IL-17RA) and IL-17RC are expressed on the surface of LMVECs. In contrast to IL-17F, IL-17A significantly upregulated CXCL1 mRNA expression and protein release, whereas both IL-17A and IL-17F did not have the ability to induce CXCL5 and CXCL8 secretion in LMVECs. IL-17A and IL-17F displayed positive regulatory effects on IL-1β- induced CXCL1, CXCL5, and CXCL8 secretion. On the other hand, IL-17A enhanced the upregulating effect of TNF-α on CXCL1, CXCL5, and CXCL8 release, whereas IL-17F had a negative regulatory effect on TNF-α-mediated secretion. Th2 cytokines IL-4 and IL-13 showed an inhibitory effect on IL-1β plus IL-17A-induced CXCL1, CXCL5, and CXCL8 secretion, but displayed a positive regulatory effect on TNF-α plus IL-17A-induced secretion. These results provide evidence that Th17 cytokines IL-17A and IL-17F have a distinct regulatory role in CXCL1, CXCL5, and CXCL8 expression in LMVECs stimulated either with IL-1β or with TNF-α. Our findings also suggest that CXC chemokine secretion in LMVECs may be complicatedly regulated by Th17 cytokines, Th2 cytokines, and macrophage-associated cytokines in pathological conditions such as bronchial asthma. © 2011 Springer Science+Business Media, LLC.

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Nucleostemin and TWIST as predictive markers for recurrence after neoadjuvant chemotherapy for esophageal carcinoma

Nakajima TE, Yoshida H, Okamoto N, Nagashima K, Taniguchi H, Yamada Y, Shimoda T, Masutomi K

Cancer Science 103 （ 2 ） 233 - 238 2012年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  13479032

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We recently demonstrated that overexpression of the nucleolar GTP-binding protein nucleostemin drives the fraction of genetically-defined tumor cells that exhibit markers and tumorigenic properties of tumor initiating cells. More specifically, cells that constitutively express elevated levels of nucleostemin exhibit increased TWIST expression; expression of genes that induced pluripotent stem cells; enhanced radioresistance; tumor formation, even when small numbers of cells are implanted; and an increased propensity to metastasize. An immunohistochemical analysis of cancer stem cell markers, such as nucleostemin and TWIST has not been conducted in surgically-resected esophageal squamous cell carcinomas after neoadjuvant chemotherapy. In the present study, we examined the expression of CD133, CD44, nucleostemin, guanine nucleotide-binding protein-like 3-like, and TWIST by immunohistochemistry in a series of 54 surgically-resected specimens of esophageal squamous cell carcinomas after neoadjuvant chemotherapy. We identified that high nucleostemin proportion, TWIST intensity, and advanced pathological N stage were significantly correlated with poor relapse-free survival. Together, these observations imply nucleostemin and TWIST as the predictive markers for postoperative recurrence. © 2011 Japanese Cancer Association.

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フェンタニル貼付剤の粘着性に関する検討―貼付試験と粘着性による評価―

大島新司, 間祐太朗, 長島健悟, 田中享, 佐野元彦, 太田昌一郎, 細谷治, 安野伸浩, 從二和彦

日本緩和医療薬学雑誌 5   7 - 13 2012年01月

研究論文（学術雑誌）, 共著, 査読有り

A modified maximum contrast method for unequal sample sizes in pharmacogenomic studies

Nagashima K, Sato Y, Hamada C

Statistical Applications in Genetics and Molecular Biology 10 （ 1 ） Article 41 2011年09月

研究論文（学術雑誌）, 共著, 査読有り

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Characteristics and outcomes of patients with advanced gastric cancer who declined to participate in a randomized clinical chemotherapy trial

Tanai C, Nakajima TE, Nagashima K, Kato K, Hamaguchi T, Yamada Y, Muro K, Shirao K, Kunitoh H, Matsumura Y, Yamamoto S, Shimada Y

Journal of Oncology Practice 7 （ 3 ） 148 - 153 2011年05月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  15547477

　概要を見る

Purpose: There is insufficient data to verify whether participation in clinical trials in itself can lead to better clinical outcomes. We have analyzed the characteristics and outcomes of patients who declined to participate in a randomized trial in comparison with those who participated in the trial. Patients and Methods: A randomized trial for naive advanced gastric cancer was offered to 286 patients. The trial investigated the superiority of irinotecan plus cisplatin and the noninferiority of S-1 compared with continuous fluorouracil infusion. We retrospectively reviewed the characteristics and outcomes for both participants and nonparticipants in this trial. Results: Of the 286 patients, 98 (34%) declined to participate in the trial. The rate of declining was significantly higher amongyounger patients (P = .003), and it varied significantly between attending physicians (range, 23% to 58%; P = .004). There were no other significant correlations between rate of declining and patient characteristics. No significant differences were observed in the clinical outcomes between the participants and nonparticipants, for whom the median survival times were 367 versus 347 days, respectively. The hazard ratio for overall survival, adjusted for other confounding variables, was 1.21 (95% CI, 0.91 to 1.60). No interaction was observed between participation and the various regimens. Conclusion: There was no difference in clinical outcomes between participants and nonparticipants. However, the patient's age and the doctor-patient relationship may have an effect on patient accrual to randomized trials. Copyright © 2011 by American Society of Clinical Oncology.

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Progression-free survival in first-line chemotherapy is a prognostic factor in second-line chemotherapy in patients with advanced gastric cancer

Hashimoto K, Takashima A, Nagashima K, Okazaki S, Nakajima TE, Kato K, Hamaguchi T, Yamada Y, Shimada Y

Journal of Cancer Research and Clinical Oncology 136 （ 7 ） 1059 - 1064 2010年07月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  01715216

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Purpose: First-line chemotherapy (Cx-1) in advanced gastric cancer (AGC) provides survival benefit. However, it is unclear who should proceed to second-line chemotherapy (Cx-2). Methods: We reviewed patients who received Cx-2 for AGC following progressive disease after Cx-1 from 2000 to 2005 at the National Cancer Center Hospital, Tokyo. To evaluate the prognostic factors in Cx-2, Cox regression multivariate analysis was performed. Results: Of 995 patients who received Cx-1 in this study period, 466 met the eligibility criteria. The median progression-free survival in Cx-1 (PFS-1) was 133 days. The median survival time from the date of starting second-line chemotherapy (MST-2) was 207 days. Multivariate analysis revealed that the factors affecting short survival time in Cx-2 were poor performance status (>2), low serum albumin level (<3.5 mg/dL), elevated C-reactive protein level (>1.0 mg/dL), patients with bone, liver or peritoneal metastasis, and patients without previous gastrectomy (p < 0.01). PFS-1 was an independent prognostic factor for survival (PFS-1 <120, MST-2 133 days, PFS-1 >120, MST-2 258 days, hazard ratio 0.71, 95% confidence interval 0.58-0.86, p < 0.01). The Cx-2 regimen (irinotecan vs. taxane) did not correlate with survival. Conclusion: PFS-1 is one of the prognostic factors of Cx-2 in patients with AGC. © 2010 Springer-Verlag.

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A new statistical screening approach for finding pharmacokinetics-related genes in genome-wide studies

Sato Y, Laird NM, Nagashima K, Kato R, Hamano T, Yafune A, Kaniwa N, Saito Y, Sugiyama E, Kim S-R, Furuse J, Ishii H, Ueno H, Okusaka T, Saijo N, Sawada J-i, Yoshida T

The Pharmacogenomics Journal 9 （ 2 ） 137 - 146 2009年04月

研究論文（学術雑誌）, 共著, 査読有り

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