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Untitled Document
CANCER GENOMICS & PROTEOMICS
Volume 4, Number
2, March-April 2007
| CONTENTS |
PAGE |
| Discovery of Oral Fluid Biomarkers for Human Oral Cancer by Mass Spectrometry. S. HU, T. YU, Y. XIE, Y. YANG, Y. LI, X. ZHOU, S. TSUNG, R.R. LOO, J.A. LOO, D.T. WONG (Los Angeles, CA, USA) |
55 |
| *Immunogenic Chemotherapy: Discovery of a Critical Protein through Proteomic Analyses of Tumor Cells. L. APETOH, M. OBEID, A. TESNIERE, F. GHIRINGHELLI, G.M. FIMIA, M. PIACENTINI, G. KROEMER, L. ZITVOGEL (Villejuif, France; Rome, Italy) |
65 |
| The N-terminal 15-48 Region of Cyclin Kinase Inhibitor p21 is a Determinant of Basal Expression. N. NOMURA, F. YAMAGUCHI, K. FUKUCHI (Tokyo, Japan) |
71 |
| *Pharmacogenomics of a Traditional Japanese Herbal Medicine (Kampo) for Cancer Therapy. T. EFFERTH, H. MIYACHI, H. BARTSCH (Heidelberg, Germany; Isehara, Japan) |
81 |
| Diallyl Disulfide Induced Signal Transducer and Activator of Transcription 1 Expression in Human Colon Cancer Colo 205 Cells using Differential Display RT-PCR. H.-F. LU, J.-S. YANG, Y.-T. LIN, T.-W. TAN, S.-W. IP, Y.-C. LI, M.-F. TSOU, J.-G. CHUNG (Taipei; Taichung, Taiwan) |
93 |
| *DNA Damage Response: The Players, the Network and the Role in Tumor Suppression R. RAI, G. PENG, K. LI and S-Y. LIN (Mumbai, India; Houston, TX, USA) |
99 |
*Review
CANCER GENOMICS & PROTEOMICS 4: 55-64 (2007)
Discovery of Oral Fluid Biomarkers for Human Oral Cancer by Mass Spectrometry
SHEN HU1,2, TIANWEI YU1, YONGMING XIE3, YANAN YANG3,
YANG LI1, XIAOFENG ZHOU1,5, STEPHANIE TSUNG1,
RACHEL R. LOO2,4,6, JOSEPH A. LOO2-6 and DAVID T. WONG1,5-8
1School of Dentistry and Dental Research Institute,2Mass Spectrometry and Proteomics Center, 3Department of Chemistry and Biochemistry, 4Department of Biological Chemistry,
5Jonsson Comprehensive Cancer Center, 6Molecular Biology Institute, 7Division of Head and Neck Surgery/Otolaryngology, School of Medicine and 8Henry Samueli School of Engineering and Applied Science, University of California Los Angeles, Los Angeles, CA, U.S.A.
Abstract: Proteomic analysis of human oral fluid (whole saliva) holds promise as a non-invasive method to identify biomarkers for human oral cancer, a high impact local disease in the oral cavity affecting 38,000 Americans and with 350,000 cases worldwide annually. In this study, matrix-assisted laser desorption/ionization - mass spectrometry (MALDI-MS) was used to profile oral fluid samples from oral cancer and control subjects, and 46 peptides/proteins were found at significantly different levels between the two groups. To identify a candidate protein biomarker, oral fluid samples were separated by liquid chromatography (LC) using a C4 reversed-phase column. The collected LC fractions were monitored by MALDI-MS and the fraction containing the candidate biomarker was digested for LC-MS/MS analysis to identify it. The use of nanospray MS/MS for the identification of candidate peptide biomarkers was also demonstrated. This approach can be useful for the identification of protein or peptide biomarkers following MALDI-MS or surface-enhanced laser desorption/ionization MS profiling of clinical samples. This study clearly demonstrated that oral fluid contains proteomic signatures that may serve as biomarkers for human diseases such as oral cancer. Once discovered and validated on a large and independent clinical cohort, oral fluid proteomic biomarkers may be extensively used for future disease diagnosis.
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CANCER GENOMICS & PROTEOMICS 4: 65-70 (2007)
Immunogenic Chemotherapy: Discovery of a Critical Protein through Proteomic Analyses of Tumor Cells
LIONEL APETOH1,2,3, MICHEL OBEID1,2,4, ANTOINE TESNIERE1,2,4,
FRANÇOIS GHIRINGHELLI1,2,3, GIAN MARIA FIMIA5,
MAURO PIACENTINI1,2,4, GUIDO KROEMER1,2,4
and LAURENCE ZITVOGEL1,2,3
1Institut Gustave Roussy, Villejuif;
2Faculte Paris Sud-Université Paris XI, Villejuif;
3Institut National de la Santé et de la Recherche Médicale, U805, CIC BT507, Villejuif;
4Institut National de la Santé et de la Recherche Médicale, U848, Villejuif, France;
5National Institute for Infectious Diseases Lazzaro Spallanzani, Via Portuense 292, I-00149 Rome, Italy
Abstract: The aim of chemotherapy and radiotherapy is to eliminate tumor cells. While the outcomes of these cytotoxic treatments have previously been assigned to their direct effects on tumor cells, recent findings have shown that the host's immune system also contributes to the success of chemotherapeutic and radiotherapeutic regimens. The finding that some cytotoxic antitumor coumpounds such as anthracyclines were capable of triggering a potent T-cell-dependent antitumor response has prompted the search for molecular determinants responsible for the immunogenicity of anthracyclines. Proteomic analyses of anthracycline-treated tumor cells have recently revealed the critical involvement of calreticulin in mediating the immunogenicity of dying tumor cells. Here, we focused on the molecular study of immunogenic chemotherapy which led to the characterization of calreticulin as a critical protein in immunogenic cancer cell death.
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CANCER GENOMICS & PROTEOMICS 4: 71-80 (2007)
The N-terminal 15-48 Region of Cyclin Kinase Inhibitor p21 is a Determinant of Basal Expression
NORIHIRO NOMURA, FUMIHIRO YAMAGUCHI and KUNIHIKO FUKUCHI
Department of Clinical Pathology, Showa University, School of Medicine,
Shinagawa, Tokyo, Japan
Abstract: The cyclin kinase inhibitor, p21, inhibits or arrests cell cycle progression in response to DNA damage and regulates the progression of apoptosis, either negatively or positively depending on the situation. The stability of p21 is regulated by its phosphorylation or through binding with partner molecules, and, when cells grow without DNA damage, the level of p21 is regulated by proteasome degradation. In this study, we analyzed the mechanism by which the basal expression level of p21 is stabilized. The transient expression of various p21 deletion mutants revealed a specific mutant with a deletion of 15-48 aa (Δ15-48C) that was extremely unstable. This mutant was stabilized by the proteasome inhibitor, lactacystin. Since the cysteine in the region of the alanine mutant did not destabilize p21, possible disulfide bonds formed by cysteines in the region are not responsible for the stabilization. The Δ15-48C was unstable in the cells stably expressing the 1-60 aa region, indicating that the 1-60 aa region did not function in trans. Fusion of the 1-60 aa fragment to the N-terminal of Δ15-48C stabilized the product, indicating that the 1-60 aa region in the molecule is effective for the stabilization. We constructed cells that stably expressed Δ15-48C. The Δ15-48C was unstable, but was stabilized by lactacystin. Irradiation (5 Gy) enhanced the expression of Δ15-48C without elevation of mRNA levels and increased the binding with cyclin A or CDK2. Taken together, the 15-48 aa region of p21 is essential for basal expression by preventing degradation by the proteasome, which is distinct from the mechanism induced by DNA damage.
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CANCER GENOMICS & PROTEOMICS 4: 81-92 (2007)
Pharmacogenomics of a Traditional Japanese Herbal Medicine (Kampo) for Cancer Therapy
THOMAS EFFERTH1, HAYATO MIYACHI2 and HELMUT BARTSCH1
1Division of Toxicology and Cancer Risk Factors, German Cancer Research
Center (DKFZ), 69120 Heidelberg, Germany;
2Department for Laboratory Medicine, Tokai University School of Medicine,
Bohseidai, Isehara, Japan
Abstract: In the present review, we give a short introduction into the history, philosophy and traditional diagnosis and therapy of Kampo, which has its origins in traditional Chinese medicine. The main focus is on pharmacogenomics of natural products derived from Kampo medicinal plants, with special emphasis on cancer treatment. One of these natural products with profound cytotoxicity against tumor cell lines is shikonin from the medicinal plant Lithospermum erythrorhizon. This compound has been selected to demonstrate how molecular determinants of response of tumor cells to Kampo-derived natural products can be investigated by microarray-based approaches. Synthetic or semi-synthetic derivatives of natural products from Kampo medicine may lead to novel drugs with improved features for cancer treatment. Kampo-derived natural products represent a valuable reservoir for individual tumour treatment strategies in the future.
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CANCER GENOMICS & PROTEOMICS 4: 93-98 (2007)
Diallyl Disulfide Induced Signal Transducer and Activatorof Transcription 1 Expression in Human Colon CancerColo 205 Cells using Differential Display RT-PCRy
HSU-FUNG LU1, JAI-SING YANG2, YUH-TZY LIN2, TZU-WEI TAN3, SIU-WAN IP4,
YU-CHING LI5, MEI-FEN TSOU6 and JING-GUNG CHUNG7,8
1Department of Clinical Pathology, Cheng Hsin Rehabilitation Medical Center, Taipei;
Departments of 2Pharmacology, 4Nutrition, 7Microbiology and
8Biological Science and Technology, China Medical University, Taichung;
3Department of Nursing and Management, Jen-the Junior College of Medicine, Taichung;
5Department of Medical Laboratory Science and Biotechnology,
Central Taiwan University of Science and Technology, Taichung;
6Department of Internal Medicine, China Medical University Hospital, Taichung,
Taiwan, R.O.C.
Abstract: Diallyl disulfide is one of the components of garlic and has been demonstrated to induce apoptosis in many cancer cell lines, though it is not reported to be associated with signal transducer and activator of transcription 1 (STAT1) expression. Moreover the role of STAT1 does not directly affect apoptosis in cancer cells after exposure to chemotherapy agents, though some reports showed that STAT1 is associated with apoptosis. In this study, differential display RT-PCR was used to examine the effects of diallyl disulfide (DADS) on human colon cancer cells (colo 205). The results demonstrated that DADS induced the expression of STAT1 which was also confirmed using Western blotting. STAT1 decoy oligonucleotides were also used to block STAT1 mRNA and led to a decrease in the levels of STAT1 and to subsequence decrease in the percentage of apoptosis induced by DADS in examined colo 205 cells.
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CANCER GENOMICS & PROTEOMICS 4: 99-106 (2007)
DNA Damage Response: The Players, the Network and the Role in Tumor Suppression
REKHA RAI1, GUANG PENG2, KAIYI LI3 and SHIAW-YIH LIN2
1ACTREC (CRI), TMC, Mumbai, Maharashtra, India;
2Department of Systems Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77054;
3Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, U.S.A.
Abstract: One of the most common features of cancer is genetic instability. In response to numerous DNA-damaging insults, normal cells have evolved a complex mechanism to monitor and repair DNA damage lesions to maintain genomic integrity. The defects in DNA damage response, indeed, have been shown to associate closely with tumorigenesis. This review provides an overview on the molecular events in DNA damage signaling pathway, including cell cycle checkpoint and DNA repair. The recent research discoveries on how dysfunction in DNA damage response contributes to genomic instability and cancer development are also discussed.
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