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Untitled Document
CANCER GENOMICS & PROTEOMICS
Volume 3, Number
1, January-February 2006
| CONTENTS |
PAGE |
| *Gene Expression and Proteomic Analysis of Pancreatic Cancer: a Recent Update. R. CHEN, S. PAN, D.A. CRISPIN, T.A. BRENTNALL (Seattle,WA, USA) |
1 |
*Proteomics and Bioinformatics in Biomedical Research. T. KISLINGER,
I. JURISICA (Toronto, ON, Canada) |
11 |
| Cytoplasmic Localization of Cyclin Kinase Inhibitor p21 Delays the Progression of Apoptosis.D. ARAI, N. NOMURA, K. FUKUCHI, K. GOMI (Tokyo, Japan) |
29 |
Loss of Chromosome 13q is Associated with Malignant Potential in Pulmonary Carcinoids. K. INAMURA, R. FURUTA, Y. SATOH, T. SHIRAKAWA,
S. OKUMURA, K. NAKAGAWA, M.I FUJIWARA, E. TSUCHIYA,
Y. ISHIKAWA (Tokyo; Yokohama, Japan) |
39 |
| Rapid and Sensitive Assay of K-ras Mutations in Pancreatic Cancer by Electrochemical Detection with Ferrocenyl-naphthalene-diimide. N. ISHIKAWA, T. MIYA, K. MIZUMOTO, K. OHUCHIDA, E. NAGAI, K. YAMAGUCHI, M. AMANO, S. TAKENAKA, M. TANAKA (Fukuoka; Chiba, Japan) |
47 |
| Down-regulation of Cdc25c, CDK1 and Cyclin B1 and Up-regulation of Wee1 by Curcumin Promotes Human Colon Cancer Colo 205 Cell Entry into G2/M-phase of Cell Cycle. C-C. SU, J-G. LIN, G-W.I CHEN, W-C. LIN, J-G. CHUNG (Taichung, Taiwan, ROC) |
55 |
Improving Gene Expression Sample Classification Using Support Vector Machine Ensembles Aggregated by Boosting. A. DRAGOMIR,
A. BEZERIANOS (Patras, Greece) |
63 |
| *Reviews
(pages 1, 11) |
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CANCER GENOMICS & PROTEOMICS 3: 29-38 (2006)
Cytoplasmic Localization of Cyclin Kinase Inhibitor p21 Delays the Progression of Apoptosis
DAISUKE ARAI, NORIHIRO NOMURA, KUNIHIKO FUKUCHI and KUNIHIDE GOMI
Department of Clinical Pathology, Showa University, School of Medicine, Tokyo 142 8666, Japan
Abstract: The different functions of the cyclin kinase inhibitor, p21, rely on its localization to either the cytoplasm or nucleus. Phosphorylation at Thr-145 and/or Ser-146 was reported to target p21 to the cytoplasm. To clarify the function of cytoplasmic p21, we constructed non-phosphorylatable mutants, Thr-145 to Ala (T145A) and Ser-146 to Ala (S146A), and phosphorylation mimic mutants, Thr-145 to Asp (T145D) and Ser-146 to Asp (S146D), and the cells stably expressing those mutants were identified. The association of all four mutants with either CyclinA or CDK2 was increased by ã-irradiation, indicating that the mutants functioned as cyclin kinase inhibitors. PCNA binding was detected in T145A and S146A, but not in T145D and S146D. In the stably-expressing cells, T145D and S146D binding was observed in the cytoplasm, while T145A and S146A in the nucleus. Further, lactacystin treatment enhanced T145A and S146A, but not T145D and S146D, which is consistent with the degradation of p21 by proteasome in the nucleus. Apoptosis induced by ã-irradiation was delayed in the cells expressing either T145D or S146D. The activities of caspase 3 were not reduced in mutant-expressing cells. These results suggest that the PCNA-unbound form of the full length p21 in the cytoplasm delays apoptosis through the interaction with caspase 3 or downstream components.
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CANCER GENOMICS & PROTEOMICS 3: 55-62 (2006)
Down-regulation of Cdc25c, CDK1 and Cyclin B1 and Up-regulation of Wee1 by Curcumin Promotes Human Colon Cancer Colo 205 Cell Entry into G2/M-phase of Cell Cycle
CHIN-CHENG SU1, JAUNG-GENG LIN1, GUANG-WEI CHEN1, WEN-CHUAN LIN2
and JING-GUNG CHUNG3,4
1School of Chinese Medicine, Departments of 2Pharmacology and
3Microbiology and 4School of Biological Science and Technology,
China Medical University, Taichung City 404, Taiwan, R.O.C.
Abstract: Background: Curcumin (diferuloylmethane) exhibited potent inhibitory activities against proliferation and induced apoptosis in several tumor cell lines. it was recently reported that curcumin induced cell cycle arrest in several human cancer cell lines. However, the exact mechanisms are unclear. Materials and Methods: Flow cytometry was used to analyze the cell cycle in human colon cancer colo 205 cells treated with various concentrations of curcumin for 48 h. In order to further understand the mechanism of curcumin-induced G2/M arrest, the checkpoint associated with enzymes of the cell cycle were also investigated by Western blotting methods. Results: Curcumin induced G2/M arrest in the examined cells and these effects were dose- and time-dependent. Futhermore, curcumin induced Wee1 expression and decreased the Cdc25c, cyclin B1 and CDK1 expressions, resulting in the induction of G2/M cell cycle arrest in the colo 205 cells. The cDNA microarray assay was also employed to confirm gene expressions (mRNA Wee1, Cdc25c, cyclin B1 and CDK1). Conclusion: The results indicate that curcumin promoted the gene expression of Wee1 and inhibited that of Cdc25c, CDK1 and cyclin B1.
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CANCER GENOMICS & PROTEOMICS 3: 1-10 (2006)
Gene Expression and Proteomic Analysis of Pancreatic Cancer: a Recent Update
RU CHEN1, SHENG PAN2, DAVID A. CRISPIN1 and TERESA A. BRENTNALL1
1GI Division / Department of Medicine, University of Washington, Seattle, WA 98195;
2Institute for Systems Biology, Seattle, WA 98103, U.S.A.
Abstract: Pancreatic cancer is a lethal disease for which little progress in early diagnosis or treatment has been made for many decades. Better biomarkers are urgently needed for early detection while the cancer is potentially curable. Recently, expression profiling, including gene expression profiling and proteomic profiling, have demonstrated new opportunities to investigate crucial events underlying pancreatic tumorigenesis and to exploit this knowledge for early detection and better intervention. This review will discuss and compare recently published data on this topic.
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CANCER GENOMICS & PROTEOMICS 3: 63-70 (2006)
Improving Gene Expression Sample Classification Using Support Vector Machine Ensembles Aggregated by Boosting
ANDREI DRAGOMIR and ANASTASIOS BEZERIANOS
Department of Medical Physics, Medical School, University of Patras, Rio 26500, Greece
Abstract: The molecular characterization of different tumor types using gene expression profiling is expected to uncover fundamental aspects related to cancer diagnosis and drug discovery. There is, therefore, a need for reliable, accurate sample classification tools, as well as methods for efficient identification of genes informative for the class discrimination. We propose a method based on Support Vector Machine (SVM) ensembles, trained within a boosting framework. The approach allows sequential training of classifiers on different data subsets, their aggregate yielding results superior to single SVM. Results from binary and multiclass classification experiments performed on several data sets are presented.
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CANCER GENOMICS & PROTEOMICS 3: 39-46 (2006)
Loss of Chromosome 13q is Associated with Malignant Potential in Pulmonary Carcinoids
KENTARO INAMURA1, REIKO FURUTA1, YUKITOSHI SATOH1,2,
TAKASHI SHIRAKAWA1,5, SAKAE OKUMURA2, KEN NAKAGAWA2,
MUTSUNORI FUJIWARA3, EIJU TSUCHIYA4 and YUICHI ISHIKAWA1
1Department of Pathology, the Cancer Institute and 2Department of Chest Surgery,
the Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR),
3-10-6 Ariake, Koto-ku, Tokyo 135-8550;
3Department of Pathology, Japanese Red Cross Medical Center, 4-1-22 Hiroo,
Shibuya-ku, Tokyo, 150-8935; 4Kanagawa Cancer Center Research Institute,
1-1-2 Nakao, Asahi-ku, Yokohama 241-0815;
5Current affiliation: Fujirebio Inc., 2-62-5, Nihombashi-hamacho,
Chuo-ku, Tokyo, 103-0007, Japan
Abstract: Background: Genetic differences between pulmonary typical carcinoids (TCs) and atypical carcinoids (ATCs) still remain controversial and no genetic marker is available for the evaluation of the malignant potential in pulmonary carcinoids. Materials and Methods: five TCs and 3 ATCs were analyzed concurrently by comparative genomic hybridization (CGH) and cytogenetics to investigate the chromosomal abnormalities with reference to malignant potential. As parameters for biological aggressiveness, mitotic counts, necrosis, lymph and blood vessel invasion, lymph node and organ metastasis and Ki-67 index were used. Results: Using CGH analysis, chromosome 13q loss was observed in 4 cases, of which 3 were ATC cases and 1 was a TC case with aggressive features. All the cases without 13q loss showed no aggressive features. Upon immunohistochemical analysis, RB protein expression was detected regardless of the 13q status. Conclusion: The results of this study indicate that another tumor suppressor gene on 13q may be involved in the malignant potential in pulmonary carcinoids.
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CANCER GENOMICS & PROTEOMICS 3: 11-28 (2006)
Proteomics and Bioinformatics in Biomedical Research
THOMAS KISLINGER1 and IGOR JURISICA2,3
1Program in Proteomics and Bioinformatics, Banting and Best Institute
of Medical Research and
2Departments of Computer Science and Medical Biophysics, University of Toronto, ON;
3Ontario Cancer Institute, Toronto Medical Discovery Tower, Toronto, ON, Canada
Abstract: Proteomics, the science of globally detecting proteins in cells, tissues or organisms under defined conditions, has greatly benefited from recent developments in mass spectrometry (MS). It is now possible to detect hundreds to thousands of proteins with high confidence in a single experiment. In this review, the basic MS technologies, currently used by laboratories around the world to identify proteins in complex biological samples, are summarized. Further, a short overview of useful separation strategies to minimize the initial complexity of biological samples, and the multitude of bioinformatics tools essential to manage large-scale proteomics data to obtain meaningful biological insight, is provided. Finally, recent advances in three main areas of medical proteomics are summarized: proteomics in cancer research, proteomics of the heart and proteomics in diabetes research.
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CANCER GENOMICS & PROTEOMICS 3: 47-54 (2006)
Rapid and Sensitive Assay of K-ras Mutations in PancreaticCancer by Electrochemical Detection with Ferrocenyl-naphthalene-diimide
NAMI ISHIKAWA1, TAKAHITO MIYA2, KAZUHIRO MIZUMOTO1,
KENOKI OHUCHIDA1, EISHI NAGAI1, KOJI YAMAGUCHI1,
MASAHIKO AMANO2, SHIGEORI TAKENAKA3
and MASAO TANAKA1
1Department of Surgery and Oncology, Graduate School of Medical Sciences,
Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582;
2TUM gene, Inc., 3-1 Kazusa-Koito Kimitsu, Chiba 292-1149;
3Department of Material Science, Kyushu Institute of Technology, 1-1,
Sensui-cho, Tobata-ku, Kitakyushu, Fukuoka 804-8550, Japan
Abstract: The DNA chip is a very powerful tool for genetic analysis. Conventional DNA chips that utilize fluorescence detection systems are very complicated, expensive and impractical, but the electrochemical array (ECA) chip is gaining popularity. To investigate the validity of the ECA chip, which utilizes ferrocenyl-naphthalene-diimide (FND), k-ras mutations in 20 pancreatic cancer tissues were examined. DNA was isolated from 20 pancreatic cancer tissues and subjected to a 2-stage polymerase chain reaction (PCR). The k-ras mutations were detected with the ECA chip. To verify the reliability of the ECA chip, the DNA was also analyzed by direct sequencing and the PCR-dependent preferential homoduplex formation assay (PCR-PHFA). The ECA chip could detect one mutation in a background of 1000 wild-type DNAs. K-ras mutations were identified in 17 out of 20 (85%) pancreatic cancer samples. Three mutations of codon 12 of k-ras, GTT, GAT and AGT, were detected. K-ras mutations were detected in 13 out of 20 (65%) samples by sequencing and in 17 out of 20 (85%) samples by PCR-PHFA. These findings were concordant with the ECA chip result. The FND-ECA chip is a sensitive, rapid and reliable method for screening point mutations in a variety of clinical samples.
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