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Pancreatic Neoplasms: HELP
Articles by Kazufumi Honda
Based on 10 articles published since 2010
(Why 10 articles?)
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Between 2010 and 2020, Kazufumi Honda wrote the following 10 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Measurement of copy number of ACTN4 to optimize the therapeutic strategy for locally advanced pancreatic cancer. 2018

Shoji, Hirokazu / Miura, Nami / Ueno, Hideki / Honda, Kazufumi. ·Department of Biomarker for Early Detection of Cancer, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, 104-0045, Japan. · Department of Biomarker for Early Detection of Cancer, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. · Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, 104-0045, Japan. · Department of Biomarker for Early Detection of Cancer, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; Japan Agency for Medical Research and Development: AMED-CREST, AMED, Tokyo, 100-0004, Japan. Electronic address: khonda@ncc.go.jp. ·Pancreatology · Pubmed #29921500.

ABSTRACT: The standard therapeutic strategy recommended for locally advanced pancreatic cancer (LAPC) is typically chemotherapy or chemoradiotherapy (CRT). Although the clinical benefit of chemotherapy alone versus CRT for LAPC has been compared in a number of clinical trials, the optimal therapy for LAPC remains unclear. Moreover, the clinical benefit derived from treatment in each clinical trial is a matter of controversy, and the superiority of one treatment over another has yet to be definitively demonstrated. The poor outcomes seen among patients with LAPC owe largely to the emergence of metastatic disease; therefore, accurately evaluating occult distant metastasis before choosing a therapeutic strategy could be expected to help stratify patients with LAPC into the most appropriate treatment regimen, namely local control or systemic therapy. In 1998, we identified the actinin-4 gene (ACTN4) as an actin-binding protein and showed its molecular mechanisms had clinical implications for cancer metastasis. We also identified ACTN4 gene amplification in pancreatic, ovarian, and salivary gland cancer, and demonstrated its utility as a strong prognostic biomarker for stage I lung adenocarcinoma in patients who had never received chemotherapy. Moreover, we recently reported that ACTN4 gene amplification could be a useful biomarker for predicting the efficacy of CRT for LAPC. In the present review, we summarize current knowledge regarding therapeutic strategies for LAPC and discuss the potential development of personalized medicine using ACTN4 measurement for patients with LAPC.

2 Review Potential usefulness of apolipoprotein A2 isoforms for screening and risk stratification of pancreatic cancer. 2016

Honda, Kazufumi / Srivastava, Sudhir. ·Division of Chemotherapy & Clinical Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan. · Japan Agency for Medical Research & Development (AMED) CREST, Tokyo 100-0004, Japan. · Division of Cancer Prevention, National Cancer Institute, Rockville, MD 20852, USA. ·Biomark Med · Pubmed #27673558.

ABSTRACT: Given the low incidence of pancreatic cancer in the general population, screening of pancreatic cancer in the general population using invasive modalities is not feasible. Combination of invasive screening with noninvasive biomarkers for pancreatic cancer and its precancerous lesions has the potential to reduce mortality due to pancreatic cancer. In this review, we focus on biomarkers found in the blood that can indicate early-stage pancreatic cancer, and we discuss current strategies for screening for pancreatic cancer. We recently identified a unique alteration in apolipoprotein A2 isoforms in pancreatic cancer and its precancerous lesions, and we describe its clinical usefulness as a potential biomarker for the early detection and risk stratification of pancreatic cancer.

3 Clinical Trial Identification of IGFBP2 and IGFBP3 As Compensatory Biomarkers for CA19-9 in Early-Stage Pancreatic Cancer Using a Combination of Antibody-Based and LC-MS/MS-Based Proteomics. 2016

Yoneyama, Toshihiro / Ohtsuki, Sumio / Honda, Kazufumi / Kobayashi, Makoto / Iwasaki, Motoki / Uchida, Yasuo / Okusaka, Takuji / Nakamori, Shoji / Shimahara, Masashi / Ueno, Takaaki / Tsuchida, Akihiko / Sata, Naohiro / Ioka, Tatsuya / Yasunami, Yohichi / Kosuge, Tomoo / Kaneda, Takashi / Kato, Takao / Yagihara, Kazuhiro / Fujita, Shigeyuki / Huang, Wilber / Yamada, Tesshi / Tachikawa, Masanori / Terasaki, Tetsuya. ·Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. · Department of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. · Japan Agency for Medical Research and Development (AMED) CREST, Tokyo, Japan. · Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo, Japan. · Division of Epidemiology, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Departments of Hepato-Biliary-Pancreatic Surgery, Osaka National Hospital, National Hospital Organization, Osaka, Japan. · Department of Oral Surgery, Osaka Medical College, Osaka, Japan. · Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan. · Department of Surgery, Jichi Medical University, Tochigi, Japan. · Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. · Islet Institute, Fukuoka University, Fukuoka, Japan. · Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan. · Department of Radiology, Nihon University School of Dentistry at Matsudo, Chiba, Japan. · Department of Oral Implant, Nihon University School of Dentistry at Matsudo, Chiba, Japan. · Department of Oral Surgery, Saitama Cancer Center, Saitama, Japan. · Department of Oral and Maxillofacial Surgery, Wakayama Medical University, Wakayama, Japan. · Abnova, Taipei City, Taiwan. ·PLoS One · Pubmed #27579675.

ABSTRACT: Pancreatic cancer is one of the most lethal tumors, and reliable detection of early-stage pancreatic cancer and risk diseases for pancreatic cancer is essential to improve the prognosis. As 260 genes were previously reported to be upregulated in invasive ductal adenocarcinoma of pancreas (IDACP) cells, quantification of the corresponding proteins in plasma might be useful for IDACP diagnosis. Therefore, the purpose of the present study was to identify plasma biomarkers for early detection of IDACP by using two proteomics strategies: antibody-based proteomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics. Among the 260 genes, we focused on 130 encoded proteins with known function for which antibodies were available. Twenty-three proteins showed values of the area under the curve (AUC) of more than 0.8 in receiver operating characteristic (ROC) analysis of reverse-phase protein array (RPPA) data of IDACP patients compared with healthy controls, and these proteins were selected as biomarker candidates. We then used our high-throughput selected reaction monitoring or multiple reaction monitoring (SRM/MRM) methodology, together with an automated sample preparation system, micro LC and auto analysis system, to quantify these candidate proteins in plasma from healthy controls and IDACP patients on a large scale. The results revealed that insulin-like growth factor-binding protein (IGFBP)2 and IGFBP3 have the ability to discriminate IDACP patients at an early stage from healthy controls, and IGFBP2 appeared to be increased in risk diseases of pancreatic malignancy, such as intraductal papillary mucinous neoplasms (IPMNs). Furthermore, diagnosis of IDACP using the combination of carbohydrate antigen 19-9 (CA19-9), IGFBP2 and IGFBP3 is significantly more effective than CA19-9 alone. This suggests that IGFBP2 and IGFBP3 may serve as compensatory biomarkers for CA19-9. Early diagnosis with this marker combination may improve the prognosis of IDACP patients.

4 Article Trends in biomarker discoveries for the early detection and risk stratification of pancreatic cancer using omics studies. 2019

Kobayashi, Takashi / Honda, Kazufumi. ·Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine , Kobe , Hyogo , Japan. · Department of Biomarkers for Early Detection of Cancer, National Cancer Center Research Institute , Tokyo , Japan. ·Expert Rev Mol Diagn · Pubmed #31298060.

ABSTRACT: -- No abstract --

5 Article CA19-9 and apolipoprotein-A2 isoforms as detection markers for pancreatic cancer: a prospective evaluation. 2019

Honda, Kazufumi / Katzke, Verena A / Hüsing, Anika / Okaya, Shinobu / Shoji, Hirokazu / Onidani, Kaoru / Olsen, Anja / Tjønneland, Anne / Overvad, Kim / Weiderpass, Elisabete / Vineis, Paolo / Muller, David / Tsilidis, Kostas / Palli, Domenico / Pala, Valeria / Tumino, Rosario / Naccarati, Alessio / Panico, Salvatore / Aleksandrova, Krasimira / Boeing, Heiner / Bueno-de-Mesquita, H Bas / Peeters, Petra H / Trichopoulou, Antonia / Lagiou, Pagona / Khaw, Kay-Tee / Wareham, Nick / Travis, Ruth C / Merino, Susana / Duell, Eric J / Rodríguez-Barranco, Miguel / Chirlaque, María Dolores / Barricarte, Aurelio / Rebours, Vinciane / Boutron-Ruault, Marie-Chiristine / Romana Mancini, Francesca / Brennan, Paul / Scelo, Ghislaine / Manjer, Jonas / Sund, Malin / Öhlund, Daniel / Canzian, Federico / Kaaks, Rudolf. ·Department of Biomarker for Early Detection of Cancer, National Cancer Center Research Institute, Tokyo, Japan. · Japan Agency for Medical Research and Development (AMED) CREST, Tokyo, Japan. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan. · Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. · Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. · Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. · Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. · Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. · Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece. · Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy. · Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. · Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, Ragusa, Italy. · Department of Molecular and Genetic Epidemiology, IIGM - Italian Institute for Genomic Medicine, Torino, Italy. · Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. · Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. · Department of Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. · Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands. · MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom. · Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens, School of Medicine, WHO Collaborating Center for Nutrition and Health. · Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. · Cancer Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom. · MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · Public Health Directorate, Asturias, Spain, Acknowledgment of funds: Regional Government of Asturias. · PanC4 Consortium, Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. · Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. · CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain. · Department of Epidemiology, Murcia Regional Health Council, CIBER Epidemiología y Salud Pública (CIBERESP), Spain, Ronda de Levante, Murcia, Spain. · Navarra Public Health Institute, Pamplona, Spain. · IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. · Pancreatology Unit, Beaujon Hospital, Clichy, France. · INSERM - UMR 1149, University Paris 7, Paris, France. · CESP, INSERM U1018, Univ. Paris-Sud, UVSQ, Université Paris-Saclay, Villejuif, France. · Lifestyle, Genes and Health: Integrative Trans-Generational Epidemiology, Gustave Roussy, Villejuif, France. · Section of Genetics, International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France. · Department of Surgery, Skåne University Hospital, Lund University, Lund, Sweden. · Department of Surgical and Preoperative Sciences, Umeå University, Umeå, Sweden. · Department of Radiation Sciences and Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden. · Genomic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. ·Int J Cancer · Pubmed #30259989.

ABSTRACT: Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. Our study provides a first prospective evaluation of an ApoA2 isoform ("ApoA2-ATQ/AT"), alone and in combination with carbohydrate antigen 19-9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6-18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6-18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤ 18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6-18 or ≤ 18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging.

6 Article Identification of highly sensitive biomarkers that can aid the early detection of pancreatic cancer using GC/MS/MS-based targeted metabolomics. 2017

Hirata, Yuichi / Kobayashi, Takashi / Nishiumi, Shin / Yamanaka, Kodai / Nakagawa, Takashi / Fujigaki, Seiji / Iemoto, Takao / Kobayashi, Makoto / Okusaka, Takuji / Nakamori, Shoji / Shimahara, Masashi / Ueno, Takaaki / Tsuchida, Akihiko / Sata, Naohiro / Ioka, Tatsuya / Yasunami, Yohichi / Kosuge, Tomoo / Kaneda, Takashi / Kato, Takao / Yagihara, Kazuhiro / Fujita, Shigeyuki / Yamada, Tesshi / Honda, Kazufumi / Azuma, Takeshi / Yoshida, Masaru. ·Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan. · Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Departments of Hepato-Biliary-Pancreatic Surgery, Osaka National Hospital, National Hospital Organization, Osaka, Japan. · Department of Oral Surgery, Osaka Medical College, Osaka, Japan. · Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan. · Department of Surgery, Jichi Medical University, Tochigi, Japan. · Department of GI Cancer Screening and Surveillance, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. · Islet Institute, Fukuoka University, Fukuoka, Japan. · Department of Gastrointestinal Surgery, JR Tokyo General Hospital, Tokyo, Japan. · Department of Radiology, Nihon University School of Dentistry at Matsudo, Chiba, Japan. · Department of Oral Implant, Nihon University School of Dentistry at Matsudo, Chiba, Japan. · Department of Oral Surgery, Saitama Cancer Center, Saitama, Japan. · Department of Oral and Maxillofacial Surgery, Wakayama Medical University, Wakayama, Japan. · Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo, Japan; Japan Agency for Medical Research and Development (AMED) CREST, Tokyo, Japan. · Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan; Metabolomics Research, Department of Internal Related, Kobe University Graduate School of Medicine, Hyogo, Japan; AMED-CREST, AMED, Hyogo, Japan. Electronic address: myoshida@med.kobe-u.ac.jp. ·Clin Chim Acta · Pubmed #28215548.

ABSTRACT: BACKGROUND: To improve prognosis of pancreatic cancer (PC) patients, the discovery of more reliable biomarkers for the early detection is desired. METHODS: Blood samples were collected by 2 independent groups. The 1st set was included 55 early PC and 58 healthy volunteers (HV), and the 2nd set was included 16 PC and 16HV. The 16 targeted metabolites were quantitatively analyzed by gas chromatography/tandem mass spectrometry together with their corresponding stable isotopes. In the 1st set, the levels of these metabolites were evaluated, and diagnostic models were constructed via multivariate logistic regression analysis, leading to validation using the 2nd set. RESULTS: In the 1st set, model X consisting of 4 candidates based on our previous report possessed higher sensitivity (74.1%) than carbohydrate antigen 19-9 (CA19-9). Model Y, consisting of 2 metabolites newly selected from 16 metabolites via stepwise method possessed higher sensitivity (70.4%) than CA19-9. Furthermore, combining model Y with CA19-9 increased its sensitivity (90.7%) and specificity (89.5%). In the 2nd set, combining model Y with CA19-9 displayed high sensitivity (81.3%) and specificity (93.8%). In particular, it displayed very high sensitivity (100%) for resectable PC. CONCLUSIONS: Quantitative analysis confirmed that metabolomics-based diagnostic methods are useful for detecting PC early.

7 Article Plasma biomarker for detection of early stage pancreatic cancer and risk factors for pancreatic malignancy using antibodies for apolipoprotein-AII isoforms. 2015

Honda, Kazufumi / Kobayashi, Michimoto / Okusaka, Takuji / Rinaudo, Jo Ann / Huang, Ying / Marsh, Tracey / Sanada, Mitsuaki / Sasajima, Yoshiyuki / Nakamori, Shoji / Shimahara, Masashi / Ueno, Takaaki / Tsuchida, Akihiko / Sata, Naohiro / Ioka, Tatsuya / Yasunami, Yohichi / Kosuge, Tomoo / Miura, Nami / Kamita, Masahiro / Sakamoto, Takako / Shoji, Hirokazu / Jung, Giman / Srivastava, Sudhir / Yamada, Tesshi. ·Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan. · Japan Agency for Medical Research and Development (AMED) CREST, Tokyo 100-0004, Japan. · Toray Industries, Inc., New Frontiers Research Labs, Kanagawa 248-8555, Japan. · Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo 104-0045, Japan. · National Cancer Institute, Division of Cancer Prevention, Rockville, MD 20852, USA. · Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle 98109-1024, WA, USA. · Department of Surgery, Osaka National Hospital, National Hospital Organization, Osaka 540-0006, Japan. · Department of Oral Surgery, Osaka Medical College, Osaka 569-8686, Japan. · Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo 160-0023, Japan. · Department of Surgery, Jichi Medical University, Tochigi 329-0498, Japan. · Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-0025, Japan. · Department of Regenerative Medicine and Transplantation, Fukuoka University Faculty of Medicine, Fukuoka 814-0018, Japan. · Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo 104-0045, Japan. ·Sci Rep · Pubmed #26549697.

ABSTRACT: We recently reported that circulating apolipoprotein AII (apoAII) isoforms apoAII-ATQ/AT (C-terminal truncations of the apoAII homo-dimer) decline significantly in pancreatic cancer and thus might serve as plasma biomarkers for the early detection of this disease. We report here the development of novel enzyme-linked immunosorbent assays (ELISAs) for measurement of apoAII-ATQ/AT and their clinical applicability for early detection of pancreatic cancer. Plasma and serum concentrations of apoAII-ATQ/AT were measured in three independent cohorts, which comprised healthy control subjects and patients with pancreatic cancer and gastroenterologic diseases (n = 1156). These cohorts included 151 cases of stage I/II pancreatic cancer. ApoAII-ATQ/AT not only distinguished the early stages of pancreatic cancer from healthy controls but also identified patients at high risk for pancreatic malignancy. AUC values of apoAII-ATQ/AT to detect early stage pancreatic cancer were higher than those of CA19-9 in all independent cohorts. ApoAII-ATQ/AT is a potential biomarker for screening patients for the early stage of pancreatic cancer and identifying patients at risk for pancreatic malignancy (161 words).

8 Article Altered plasma apolipoprotein modifications in patients with pancreatic cancer: protein characterization and multi-institutional validation. 2012

Honda, Kazufumi / Okusaka, Takuji / Felix, Klaus / Nakamori, Shoji / Sata, Naohiro / Nagai, Hideo / Ioka, Tatsuya / Tsuchida, Akihiko / Shimahara, Takeshi / Shimahara, Masashi / Yasunami, Yohichi / Kuwabara, Hideya / Sakuma, Tomohiro / Otsuka, Yoshihiko / Ota, Norihito / Shitashige, Miki / Kosuge, Tomoo / Büchler, Markus W / Yamada, Tesshi. ·Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo, Japan. ·PLoS One · Pubmed #23056525.

ABSTRACT: BACKGROUND: Among the more common human malignancies, invasive ductal carcinoma of the pancreas has the worst prognosis. The poor outcome seems to be attributable to difficulty in early detection. METHODS: We compared the plasma protein profiles of 112 pancreatic cancer patients with those of 103 sex- and age-matched healthy controls (Cohort 1) using a newly developed matrix-assisted laser desorption/ionization (oMALDI) QqTOF (quadrupole time-of-flight) mass spectrometry (MS) system. RESULTS: We found that hemi-truncated apolipoprotein AII dimer (ApoAII-2; 17252 m/z), unglycosylated apolipoprotein CIII (ApoCIII-0; 8766 m/z), and their summed value were significantly decreased in the pancreatic cancer patients [P = 1.36×10(-21), P = 4.35×10(-14), and P = 1.83×10(-24) (Mann-Whitney U-test); area-under-curve values of 0.877, 0.798, and 0.903, respectively]. The significance was further validated in a total of 1099 plasma/serum samples, consisting of 2 retrospective cohorts [Cohort 2 (n = 103) and Cohort 3 (n = 163)] and a prospective cohort [Cohort 4 (n = 833)] collected from 8 medical institutions in Japan and Germany. CONCLUSIONS: We have constructed a robust quantitative MS profiling system and used it to validate alterations of modified apolipoproteins in multiple cohorts of patients with pancreatic cancer.

9 Article Reduced plasma level of CXC chemokine ligand 7 in patients with pancreatic cancer. 2011

Matsubara, Junichi / Honda, Kazufumi / Ono, Masaya / Tanaka, Yoshinori / Kobayashi, Michimoto / Jung, Giman / Yanagisawa, Koji / Sakuma, Tomohiro / Nakamori, Shoji / Sata, Naohiro / Nagai, Hideo / Ioka, Tatsuya / Okusaka, Takuji / Kosuge, Tomoo / Tsuchida, Akihiko / Shimahara, Masashi / Yasunami, Yohichi / Chiba, Tsutomu / Hirohashi, Setsuo / Yamada, Tesshi. ·Chemotherapy Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. ·Cancer Epidemiol Biomarkers Prev · Pubmed #21148121.

ABSTRACT: BACKGROUND: Early detection is essential to improve the outcome of patients with pancreatic cancer. A noninvasive and cost-effective diagnostic test using plasma/serum biomarkers would facilitate the detection of pancreatic cancer at the early stage. METHODS: Using a novel combination of hollow fiber membrane-based low-molecular-weight protein enrichment and LC-MS-based quantitative shotgun proteomics, we compared the plasma proteome between 24 patients with pancreatic cancer and 21 healthy controls (training cohort). An identified biomarker candidate was then subjected to a large blinded independent validation (n = 237, validation cohort) using a high-density reverse-phase protein microarray. RESULTS: Among a total of 53,009 MS peaks, we identified a peptide derived from CXC chemokine ligand 7 (CXCL7) that was significantly reduced in pancreatic cancer patients, showing an area under curve (AUC) value of 0.84 and a P value of 0.00005 (Mann-Whitney U test). Reduction of the CXCL7 protein was consistently observed in pancreatic cancer patients including those with stage I and II disease in the validation cohort (P < 0.0001). The plasma level of CXCL7 was independent from that of CA19-9 (Pearson's r = 0.289), and combination with CXCL7 significantly improved the AUC value of CA19-9 to 0.961 (P = 0.002). CONCLUSIONS: We identified a significant decrease of the plasma CXCL7 level in patients with pancreatic cancer, and combination of CA19-9 with CXCL7 improved the discriminatory power of the former for pancreatic cancer. IMPACT: The present findings may provide a new diagnostic option for pancreatic cancer and facilitate early detection of the disease.

10 Article Survival prediction for pancreatic cancer patients receiving gemcitabine treatment. 2010

Matsubara, Junichi / Ono, Masaya / Honda, Kazufumi / Negishi, Ayako / Ueno, Hideki / Okusaka, Takuji / Furuse, Junji / Furuta, Koh / Sugiyama, Emiko / Saito, Yoshiro / Kaniwa, Nahoko / Sawada, Junichi / Shoji, Ayako / Sakuma, Tomohiro / Chiba, Tsutomu / Saijo, Nagahiro / Hirohashi, Setsuo / Yamada, Tesshi. ·Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan. mail: jmatsuba@ncc.go.jp. ·Mol Cell Proteomics · Pubmed #20061307.

ABSTRACT: Although gemcitabine monotherapy is the standard treatment for advanced pancreatic cancer, patient outcome varies significantly, and a considerable number do not benefit adequately. We therefore searched for new biomarkers predictive of overall patient survival. Using LC-MS, we compared the base-line plasma proteome between 29 representative patients with advanced pancreatic cancer who died within 100 days and 31 patients who survived for more than 400 days after receiving at least two cycles of the same gemcitabine monotherapy. Identified biomarker candidates were then challenged in a larger cohort of 304 patients treated with the same protocol using reverse-phase protein microarray. Among a total of 45,277 peptide peaks, we identified 637 peaks whose intensities differed significantly between the two groups (p < 0.001, Welch's t test). Two MS peaks with the highest statistical significance (p = 2.6 x 10(-4) and p = 5.0 x 10(-4)) were revealed to be derived from alpha(1)-antitrypsin and alpha(1)-antichymotrypsin, respectively. The levels of alpha(1)-antitrypsin (p = 8.9 x 10(-8)) and alpha(1)-antichymotrypsin (p = 0.001) were significantly correlated with the overall survival of the 304 patients. We selected alpha(1)-antitrypsin (p = 0.0001), leukocyte count (p = 0.066), alkaline phosphatase (p = 8.3 x 10(-8)), and performance status (p = 0.003) using multivariate Cox regression analysis and constructed a scoring system (nomogram) that was able to identify a group of high risk patients having a short median survival time of 150 days (95% confidence interval, 123-187 days; p = 2.0 x 10(-15), log rank test). The accuracy of this model for prognostication was internally validated and showed good calibration and discrimination with a bootstrap-corrected concordance index of 0.672. In conclusion, an increased level of alpha(1)-antitrypsin is a biomarker that predicts short overall survival of patients with advanced pancreatic cancer receiving gemcitabine monotherapy. Although an external validation study will be necessary, the current model may be useful for identifying patients unsuitable for the standardized therapy.