| BMP7 Induces Dormancy of Prostatic Tumor Stem Cell in Bone |
Oct 2012 |
11 pages |
| Authors:
Fei Xing; SOUTHERN ILLINOIS UNIV SPRINGFIELD
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 | Bone is the most common metastatic site for prostate cancer. The growth of the tumor cells in the bone is generally slow and they often become dormant until an appropriate microenviroment is established for their re-growth. The recent stem cell theory predicts that the metastatic cells are a small population of stem-like cells in the primary tumor. However, the precise mechanism of dormancy is virtually unknown, and identifying the responsible ... |
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| Targeting Thromboxane A2 Receptor for Antimetastasis Therapy of Breast Cancer |
Sep 2012 |
20 pages |
| Authors:
Daotai Nie; SOUTHERN ILLINOIS UNIV SPRINGFIELD
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| Dissemination and metastasis of tumor cells are major causes of morbidity and mortality in breast cancer patients. Therefore it is of vital importance to identify druggable targets to inhibit breast tumor invasion and metastasis. A critical component in the invasive growth, dissemination, and metastasis of cancer is acquisition of motility by tumor cells. Our preliminary studies suggest a novel role for the thromboxane A2 receptor (TP) in controlling breast tumor ... |
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| The Role of Tumor Associated Macrophage in Recurrent Growth of Tumor Stem Cell |
Sep 2012 |
9 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
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| According to the recent cancer stem cell (CSC) theory, recurrent tumor must arise from a dormant tumor stem cell whose re- growth is triggered by shifting of microenvironment. This project aims at clarifying the roles of TAM in recurrent growth of dormant stem cell in breast cancer. We hypothesize that the balance of dormancy and recurrence is determined by the ability of the tumor stem cells to recruit TAM which ... |
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| Identification of Dormant Stem Cell in Prostate Cancer |
Mar 2012 |
7 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
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| Recurrent disease is the most daunting aspect of cancer therapy; however, how tumor cells become dormant and later recur is poorly understood. It is of paramount importance to decipher the underlining molecular mechanism of dormancy in order to define specific targets for the treatment of recurrent metastatic disease. The overall goal of this project is to identify key factor(s) and signaling that control tumor stem cell dormancy. In this fiscal ... |
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| Nanog, Cancer Stem Cells, and Resistance to Chemotherapy |
Sep 2011 |
14 pages |
| Authors:
Hongmei Jiang; SOUTHERN ILLINOIS UNIV SPRINGFIELD
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| It is now increasingly accepted that cancer stem cells (CSCs, or tumor initiating cells) are responsible for tumor initiation. If cancer treatment kills most of cancer cells in the stage of transit amplifying and differentiation without killing the stem cells, the surviving cancer stem cells will eventually lead to recurrence of tumors. To eradicate cancer, we must learn more about the biology of cancer stem cells, their responses to treatments, ... |
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| DCIS-Specific MicroRNA in Cancer Stem Cell |
Sep 2011 |
9 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
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| More than 20% of breast cancer patients detected by mammography are DCIS and this number keeps on increasing (1). Although DCIS is a non-invasive benign tumor, it is considered a precursor of malignant cancer. Therefore, understanding the molecular changes from normal cell to DCIS is of paramount importance and it is under intensive study. However, the exact mechanism of normal-DCIS transition is still not well understood. The purpose of this ... |
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| Identification of Metastatic Tumor Stem Cell |
Sep 2011 |
9 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| More than 90% of deaths caused by breast cancer are attributed to metastatic disease. However, the exact molecular mechanism of tumor metastasis is still poorly understood. It has been well recognized that only a fraction of cells in the primary tumor eventually metastasizes to the distant organs; however, the origin and nature of these cells are still unclear. The purpose of this project is to test our novel hypothesis that ... |
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| Solidago Vigaurea for Prostate Cancer Therapy |
APR 2011 |
73 pages |
| Authors:
Kounsouke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| Adenocarcinoma of the prostate is currently the most prevalent cancer in men in the United States and represents 36% of all cancers among men (1). It is estimated that more than 210,000 new cases are diagnosed and 32,000 patients succumb to this disease every year (1). Although patients with localized lesions can be cured by radical prostatectomy or radiotherapy, more than 90% of cancer deaths are attributed to metastatic disease ... |
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| Regulatory Role of the NF-kB Pathway in Lymphangiogenesis and Breast Cancer Metastasis |
Oct 2010 |
53 pages |
| Authors:
Michael Flister; SOUTHERN ILLINOIS UNIV SPRINGFIELD
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| Elevation of VEGFR-3, the primary mediator of lymphangiogenesis (i.e., new lymphatic vessel formation), is frequently associated with inflammation related to chronic disease and cancer. In the latter case, VEGFR-3 dependent lymphangiogenesis induced by inflamed tumors increases the incidence of distant metastasis, leading to decreased patient survival. However, the molecular mechanisms underlying inflammation-induced VEGFR-3 elevation and lymphangiogenesis are currently unknown. Two potential candidate genes that may regulate expression of VEGFR-3 are ... |
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| Targeting Thromboxane A2 Receptor for Antimetastasis Therapy of Breast Cancer |
SEP 2010 |
13 pages |
| Authors:
Daotai Nie; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| Dissemination and metastasis of tumor cells are major causes of morbidity and mortality in breast cancer patients. Therefore it is of vital importance to identify druggable targets to inhibit breast tumor invasion and metastasis. A critical component in the invasive growth, dissemination, and metastasis of cancer is acquisition of motility by tumor cells. Our preliminary studies suggest a novel role for a classical G protein-coupled receptor (GPCR), the thromboxane A2 ... |
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| Identification of Metastatic Tumor Stem Cell |
Sep 2010 |
8 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| Tumor metastasis is an extremely inefficient process and only a fraction of cells in the primary tumor can successfully establish metastatic colonization. These cells by definition have a stem-like ability, but they also need to have an ability of metastasizing to other organs. Therefore, in addition to a tumor stem cell, an existence of a metastatic stem cell is predicted. Despite the critical importance of the concept, this idea has ... |
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| Solidago Virgaurea for Prostate Cancer Therapy |
Apr 2010 |
60 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| Prostate cancer is one of the most resistant tumors to chemotherapy among all adenocarcinomas, and there is virtually no effective therapeutic regimen available for this cancer. Hormonal treatment is the most effective therapy in advanced cancer, however, almost all the patients who undergo hormonal therapy inevitably develop hormone-resistant tumors. Therefore, developing a better therapeutic agent by targeting a specific gene or pathway with well-defined clinical rationale is needed. We chose ... |
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| Effect of Stromal Adipokines on Breast Cancer Development |
APR 2010 |
24 pages |
| Authors:
Richard A. Woo; SOUTHERN ILLINOIS UNIV SPRINGFIELD
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| Obesity increases the risk of breast cancer in post-menopausal women. The degree of risk increases proportionally with an increase in adiposity. There is mounting evidence that stromal cells in the tumor microenvironment make pivotal contributions to tumor progression. Adipocytes have been shown to exert their influence on breast cancer cells via two secreted adipocytokines, leptin and adiponectin. Leptin stimulates proliferation and invasiveness of breast cancer cell lines. Conversely, adiponectin is ... |
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| Effect of Stromal Adipokines on Breast Cancer Development |
Sep 2009 |
12 pages |
| Authors:
Richard A Woo; SOUTHERN ILLINOIS UNIV SPRINGFIELD
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| Obesity increases the risk of breast cancer in post-menopausal women. The degree of risk increases proportionally with an increase in adiposity. There is mounting evidence that stromal cells in the tumor microenvironment make pivotal contributions to tumor progression. Stromal adipocytes have been shown to exert their influence on breast cancer cells via two secreted adipocytokines, leptin and adiponectin. Leptin stimulates proliferation and invasiveness of breast cancer cell lines. Conversely, adiponectin ... |
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| Regulatory Role of the NF-kB Pathway in Lymphangiogenesis and Breast Cancer Mestatasis |
Jul-2009 |
33 pages |
| Authors:
Michael Flister; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| The concept of inflammation-induced lymphangiogenesis (i.e., formation of new lymphatic vessels) has long been recognized, but the molecular mechanisms remained largely unknown. The two primary mediators of lymphangiogenesis are vascular endothelial growth factor receptor-3 (VEGFR-3) and Prox1. The key factors that regulate inflammation-induced transcription are members of the NF-kB family; however, the role of NF-kB in regulation of lymphatic-specific genes has not been defined. Here, we identified VEGFR-3 and Prox1 ... |
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| Solidago Virgaurea for Prostate Cancer Therapy |
Apr 2009 |
47 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| Prostate cancer is one of the most resistant tumors to chemotherapy among all adenocarcinomas, and there is virtually no effective therapeutic regimen available for this cancer. Hormonal treatment is the most effective therapy in advanced cancer, however, almost all the patients who undergo hormonal therapy inevitably develop hormone-resistant tumors. Therefore, developing a better therapeutic agent by targeting a specific gene or pathway with well-defined clinical rationale is needed. We chose ... |
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| The Role of Tumor Metastases Suppressor Gene, Drg-1, in Breast Cancer |
Mar 2009 |
103 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| Once breast cancer is diagnosed, the most critical question is whether the disease is localized or has it already metastasized to other organs. However, the molecular basis of tumor metastasis is poorly understood as yet. The major goal of this project was to elucidate the function of the tumor metastasis suppressor gene, Drg-1/NDRG1. Toward this goal, we have set three specific aims; (i) to clarify the role of the NDRG1 ... |
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| Targeting Fatty Acid Synthase Gene for Prostate Cancer Therapy |
Oct-2008 |
6 pages |
| Authors:
Eiji Furuta; Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
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| Fatty acid synthase (FAS) is significantly over-expressed in prostate tumor cells and inhibition of FAS results in apoptosis, suggesting that FAS is an ideal target for drug development. The overarching hypothesis of this project is that a specific inhibitor for FAS dimerization will block the function of this enzyme and cause apoptosis of the tumor cell. Our specific aims are (1) to characterize the apoptotic pathway induced by FAS inhibition, ... |
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| Solidago Virgaurea for Prostate Cancer Therapy |
01-Apr-2008 |
9 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| The treatment options for prostate cancer are currently quite limited. Hormonal treatment is the most effective therapy in advanced cancer, however, virtually all the patients who undergo hormonal therapy inevitably develop hormone-resistant tumor. Traditional screening of anti-cancer drugs has been mostly dependent on growth inhibition assay for cancer cells. However, targeting a specific gene with well-defined clinical rationale will provide a better chance of developing a more effective therapeutic agent. ... |
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| The Role of Tumor Metastases Suppressor Gene, Drg-1, in Breast Cancer |
01-Mar-2008 |
48 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death among women in the US. Because metastatic disease is the major cause of death it is crucial to understand the mechanism by which tumor cells metastasize to the distant organs so that we can identify a better therapeutic target. During this funding period we had a breakthrough finding that the metastasis suppressor gene NDRG1 ... |
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| Mechanism of Tumor Metastasis Suppression by the KAI1 Gene |
FEB 2008 |
25 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| KAl1 is a tumor metastases suppressor gene which is capable of blocking the metastatic process without affecting the primary tumorigenesis. In this project we tested the hypothesize that the KAl1 protein on tumor cells interacts with gp-Fy (DARC) on the endothelial cells which activates a signal pathway of the KAl1 molecule and that this activation eventually leads to cell growth arrest of tumor cells. We originally planned to examined whether ... |
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| Mechanism of Tumor Metastasis Suppression by the KAI1 Gene |
FEB 2008 |
25 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| KAl1 is a tumor metastases suppressor gene which is capable of blocking the metastatic process without affecting the primary tumorigenesis. In this project we tested the hypothesize that the KAl1 protein on tumor cells interacts with gp-Fy (DARC) on the endothelial cells which activates a signal pathway of the KAl1 molecule and that this activation eventually leads to cell growth arrest of tumor cells. We originally planned to examined whether ... |
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| Dysregulation of RNA Interference in Breast Cancer |
JUL 2007 |
25 pages |
| Authors:
Yi-Yuan Mo; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| The newly discovered RNA interference is a novel type of gene regulation mechanism, which is required for normal expression of genes. This study tests the hypothesis that breast tumor carries dysregulated RNA interference pathways, and thus, some tumor suppressor genes will be down-regulated while other genes (e.g., oncogenes) will be up-regulated, leading to tumor cell proliferation and survival. Using real time RT-PCR, we demonstrate that microRNA-21 is overexpressed in breast ... |
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| The Role of Tumor Metastases Suppressor Gene, Drg-1, in Breast Cancer |
MAR 2007 |
78 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death among women in the US. Because metastatic disease is the major cause of death, it is crucial to understand the mechanism by which tumor cells metastasize to the distant organs so that we can identify a better therapeutic target. During this funding period, we found that the metastasis suppressor gene, Drg-1, was capable of ... |
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| Mechanism of Tumor Metastasis Suppression by the KA11 Gene |
FEB 2007 |
13 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| KAI1 is a tumor metastases suppressor gene which is capable of blocking the metastatic process without affecting the primary tumorigenesis. Based on our preliminary data, we hypothesize that the KAI1 protein on tumor cells interacts with gp-Fy on the endothelial cells, which activates a signal pathway of the KAI1 molecule, and that this activation eventually leads to cell growth arrest of tumor cells. To test this hypothesis, we will examine ... |
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| Lipoxygenase, Angiogenicity, and Prostate Cancer Radioresistance |
01 Jan 2007 |
23 pages |
| Authors:
Daotai Nie; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| Radiotherapy is a prevalent modality for the treatment of prostate tumor. Although radiation is capable of eradicating localized prostate tumors, nearly 30% of patients treated with potentially curative doses relapse at the sites of irradiation. Therefore, there is an imperative need to improve the success rate of radiotherapy for PCa. This proposal is focused on a role of 12-lipoxygenase (LOX) in modulating radiation response of PCa cells. 12-LOX catalyzes the ... |
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| Dysregulation of RNA Interference in Breast Cancer |
JUL 2006 |
20 pages |
| Authors:
Yin-Yuan Mo; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| The newly discovered RNA interference is a novel type of gene regulation mechanism, which is required for normal expression of genes. This study tests the hypothesis that breast tumor carries dysregulated RNA interference pathways, and thus, some tumor suppressor genes will be down-regulated while other genes (e.g., oncogenes) will be up-regulated, leading to tumor cell proliferation and survival. Using real time RT-PCR, we demonstrate that microRNA-21 is overexpressed in breast ... |
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| The Role of Tumor Metastases Suppressor Gene, Drg-1, in Breast Cancer |
MAR 2006 |
8 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| The proposed research aims at elucidating the function of the tumor metastasis suppressor gene, Drg-1, in the hope that we can define a specific target for novel and effective therapies to prevent metastatic disease of breast cancer. During this funding period, our major effort has been focused on Task 2b, and we identified ATF3 as a down-stream target of Drg-1 by microarray analysis. This discovery of ATF3 gene has two ... |
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| Mechanism of Tumor Metastasis Suppression by the KAI1 Gene |
FEB 2006 |
8 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| Prostate cancer is the most frequently diagnosed cancer among men in the United States. It represents approximately 7% of all cancer deaths and ranks as the second leading cause of cancer death in males. The majority of prostate cancer patients succumb to their malignancy as a result of metastatic invasion, while few patients die from their primary neoplasm. Despite significant improvement in surgical techniques and chemotherapies, none of the current ... |
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