Pancreas – National Cancer Center Research Institute (Coordinating Center)

Project Title:   Improving Early Detection of Pancreatic Cancer with a Blood Test
Cancer Site:   Pancreas
Principal Investigator(s):   Tesshi YAMADA, M.D., Ph.D.
Participating Institutions:   National Cancer Center Research Institute (Coordinating Center)

Tokyo Medical University Clinical Proteome Center

Mouse Model(s):   Under consideration
Clinical Samples:   Plasma/sera from
  • Jichi Medical School Hospital
  • Tokyo Medical University Hospital
  • National Cancer Center Research Hospital
  • Osaka Medical Center for Cancer and Cardiovascular Diseases
  • Fukuoka University Hospital
Technical Approaches:   Glycopeptide enrichment

Surface Enhanced Laser Desorption/Ionization hybrid Quadrupole Time-of-Flight Mass Spectrometry (SELDI-QqTOF-MS)

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-MS)

Two Dimensional Difference Gel Electrophoresis (2D-DIGE)

Protein/peptide quantitation using isotope-coded affinity tags (ICAT)

Two Dimensional Image Converted Analysis of nano-flow Liquid chromatography and Mass Spectrometry (2D-ICAL-MS)

Two-dimensional microflow liquid chromatography/tandem mass spectrometry (2-D microLC-MS/MS)

Brief Description of Project:

Pancreatic cancer is the fifth leading cause of cancer-related mortality in Japan and was responsible for 22260 deaths in Japan in 2004. The number has increased about 2.5 fold over the last 20 years, and will continue to increase in the future. Since the clinical manifestations of pancreatic cancer, except obstructive jaundice, are often not apparent until the advanced stages of the disease, and the anatomical location of the pancreas deep in the abdomen makes physical and ultrasonic detection of pancreatic cancer difficult, about 95% of all cases are diagnosed in stage III or IV, and the 5-year survival rate of pancreatic cancer patients is the lowest among patients with common solid tumors. Early detection by mass screening seems to be one of the most feasible strategies for improving the outcome of pancreatic cancer patients. Since the 5-year survival rate of pancreatic cancer patients with stage I, II, III, IVa, and IVb disease has been reported to be 59%, 51%, 26%, 12%, and 3%, respectively, detection of stage I or II disease would significantly improve overall patient survival.

Mass screening by computerized tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) may not be cost-effective because of the relatively low incidence of pancreatic cancer, and the long-term safety of these modalities has not been established. Thus, the development of a new diagnostic modality that enables the early detection of pancreatic cancer in a safe/non-invasive and cost-effective way is needed. Human blood serum and plasma contain a large variety of proteins, and their relative abundance and modification may precisely reflect the disease status of organs and tissues. Recent advances in MS-based proteomic technologies coupled with bioinformatics may revolutionize medical diagnosis and cancer screening. The purpose of the team is to identify new diagnostic biomarkers of pancreatic cancer by comprehensive serum/plasma protein profiling. This team is composed of clinicians and scientists specialized in proteomics and bioinformatics. A large number of serum/plasma samples will be prospectively collected from participating institutions under the same protocol. Protein profiling will be performed by using various cutting-edge technologies, such as SELDI-QqTOF-MS, MALDI-MS, 2D-DIGE, ICAT, 2D-ICAL-MS, and 2-D microLC-MS/MS.

This team is supported by the grant "Third Term Comprehensive Control Research for Cancer" from the Ministry of Health, Labor and Welfare of Japan.

Team Members and Expertise:

Kazufumi HONDA, D.D.s., Ph.D. (National Cancer Center Research Institute)
Section Head of National Cancer Center Research Institute Cancer Proteomics Project
Bioinformatics and Proteomics (SELDI-QqTOF-MS and MALDI-MS)

Tatsuya IOKA, M.D. (Osaka Medical Center for Cancer and Cardiovascular Diseases)
Chief Physician of Osaka Medical Center for Cancer and Cardiovascular Diseases
Chemotherapy and Mass Survey
Provision of Clinical Samples

Tadashi KONDO, M.D., Ph.D. (National Cancer Center Research Institute)
Section Head and Project Leader of National Cancer Center Research Institute Proteome Bioinformatics Project
Bioinformatics and Proteomics (2D DIGE)

Hideo NAGAI, M.D., Ph.D. (Jichi Medical School)
Professor of Jichi Medical School
General and Pancreatic Surgery
Provision of Clinical Samples

Toshihide NISHIMURA, Ph.D. (Tokyo Medical University)
Professor of Tokyo Medical University
Proteomics (2-D microLC-MS/MS)

Takuji OKUSAKA, M.D., Ph.D. (National Cancer Center Hospital)
Chief Physician of National Cancer Center Hospital
Hepatobiliary and Pancreatic Oncology
Provision of Clinical Samples

Masaya ONO, M.D., Ph.D. (National Cancer Center Research Institute)
Section Head of National Cancer Center Research Institute Cancer Proteomics Project
Proteomics (2D-ICAL-MS)

Miki SHITASHIGE, Ph.D. (National Cancer Center Research Institute)
Staff Scientist of National Cancer Center Research Institute Cancer Proteomics Project
Proteomics (ICAT)

Akihiko TSUCHIDA, M.D., Ph.D. (Tokyo Medical University)
Associate Professor of Tokyo Medical University
Hepatobiliary and Pancreatic Surgery
Provision of Clinical Samples

Tesshi YAMADA, M.D., Ph.D. (National Cancer Center Research Institute—Biomarker Team PI) [tyamada@ncc.go.jp]
Chief of Chemotherapy Division and Project Leader of Cancer Proteomics Project
Bioinformatics

Yohichi YASUNAMI, M.D., Ph.D. (Fukuoka University)
Associate Professor of Fukuoka University
Gastrointestinal Surgery
Provision of Clinical Samples


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