29 results on '"Zang, Xiao-Ping"'
Search Results
2. Internalizing versus non-internalizing receptors for targeting L-methioninase to cancer cells
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Zang, Xiao-Ping, Palwai, Naveen R., Pento, J. Thomas, and Harrison, Roger G.
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Cancer cells -- Research ,Breast cancer -- Research ,Breast cancer -- Care and treatment ,Prostate cancer -- Research ,Prostate cancer -- Care and treatment ,Enzymes -- Research ,Antimitotic agents -- Research ,Antineoplastic agents -- Research ,Health - Abstract
We reported previously that L-methioninase targeted to the urokinase receptor of MCF-7 breast cancer cells is significantly more effective in inhibiting cell proliferation and migration than free L-methioninase both in vitro and in vivo. L-methioninase was targeted by linking at its amino terminus to an amino-terminal fragment (ATF) of urokinase. The ATF was selected for targeting because is has previously been shown not to internalize within the cells. The present study was designed to determine the effectiveness of targeting L-methioninase to a cancer cell receptor that is internalizing in comparison with ATF-methioninase, which does not internalize. Transforming growth factor-[alpha] (TGF-[alpha]) was selected for targeting to the epidermal growth factor receptor which is overexpressed in numerous cancer cell lines and is an internalizing receptor. Two fusion proteins, ATF-methioninase and TGF-methioninase (TGF-a linked to the amino terminus of L-methioninase), were produced by recombinant methods and purified. In an in vitro culture wounding assay over 3 days to measure cell proliferation and migration of MCF-7 breast cancer cells and PC-3 prostate cancer cells, both fusion proteins inhibited the proliferation and migration of both cancer cell lines. However, the inhibition was significantly greater for ATF-methioninase compared to TGF-methioninase, especially at treatment days 2 and 3. These results indicate that, for a fixed dosage of the fusion protein, it is more advantageous to have L-methioinase bind to a receptor and remain externalized, rather than to bind to a receptor which leads to internalization of L-methioninase. Further, it may be advantageous to target other anticancer agents to the urokinase receptor on the cancer cell surface by means of the amino-terminal fragment of urokinase. Key words: Breast cancer, prostate cancer, L-methioninase, transforming growth factor-a, urokinase amino-terminal fragment, INTRODUCTION Methionine-dependence is a metabolic defect of cancer cells that is under investigation for the treatment of cancer. Many cancer cell lines have been found to have this defect [1]. [...]
- Published
- 2006
3. KGF-induced motility of breast cancer cells is dependent on Grb2 and Erk1,2
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Zang, Xiao-ping, Siwak, Doris R., Nguyen, Thi X., Tari, Ana M., and Pento, J. Thomas
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- 2004
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4. Expression of prohibitin 3′ untranslated region suppressor RNA alters morphology and inhibits motility of breast cancer cells
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Manjeshwar, Sharmila, Lerner, Megan R., Zang, Xiao-Ping, Branam, Dannielle E., Pento, J. Thomas, Lane, Mary M., Lightfoot, Stan A., Brackett, Daniel J., and Jupe, Eldon R.
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- 2004
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5. Targeting of a novel fusion protein containing methioninase to the urokinase receptor to inhibit breast cancer cell migration and proliferation
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Peron, Karine, Jones, Tara N., Gauthier, Sebastien A., Nguyen, Thao-Nguyen T., Zang, Xiao-Ping, Barriere, Magali, Prévéraud, Damien, Soliman, Charles E., Harrison, Roger G., and Pento, J. Thomas
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- 2003
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6. Keratinocyte growth factor-induced motility of breast cancer cells
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Zang, Xiao Ping and Pento, J. Thomas
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- 2000
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7. Behavioral abnormalities and apoptotic changes in neurons in mice brain following a single administration of allylnitrile
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Zang, Xiao-ping, Tanii, Hideji, Kobayashi, Katsuji, Higashi, Tomomi, Oka, Rie, Koshino, Yoshifumi, and Saijoh, Kiyofumi
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- 1999
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8. Abstracts from Japanese journal of hygiene (nihon eiseigaku zasshi) Vol.54 No.2
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Takeshita, Tatsuya, Tanii, Hideji, Zang, Xiao-Ping, Saijoh, Kiyofumi, Fujita, Yasuyuki, Kodama, Kazunori, Kasagi, Fumiyoshi, Fujita, Shoichiro, Kishimoto, Masumi, Tanihara, Shinichi, Ojima, Toshiyuki, Oki, Izumi, Nakamura, Yosikazu, Yanagawa, Hiroshi, Nose, Takayuki, Momose, Yoshito, Kaetsu, Akihiko, Ishii, Toshiya, Shibata, Kazunori, Miyazaki, Motonobu, Moriyama, Masaki, Une, Hiroshi, Katakura, Michihiro, Sugawara, Naoki, and Miyai, Masaya
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- 1999
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9. KERATINOCYTE GROWTH FACTOR STIMULATES THE MIGRATION AND PROLIFERATION OF BREAST CANCER CELLS IN A CULTURE WOUNDING MODEL
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NGUYEN, THAO-NGUYEN, ZANG, XIAO-PING, and PENTO, J.THOMAS
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- 2002
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10. Effect of Antiestrogens on EGF-Mediated Movement of Human Breast Cancer Cells.
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Tong, Gina M., Rajah, Talitha T., Zang, Xiao-Ping, Bahr, Steven J., and Pento, J. Thomas
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ESTROGEN antagonists ,BREAST cancer ,CANCER cells ,EPIDERMAL growth factor ,THERAPEUTICS - Abstract
In a previous study we compared the influence of several growth factors on breast cancer cells in culture and observed that epidermal growth factor (EGF) enhanced the invasiveness of estrogen receptor-positive breast cancer cells. The objective of the present study was to determine the influence of three unique antiestrogens on EGF-mediated movement of human breast cancer cells. The rate of movement of MCF-7 breast cancer cells was measured using time-lapse videomicroscopy (TLVM). The MCF-7 cells were pretreated with antiestrogen (either tamoxifen, ICI-182-780 (ICI) or 1,1-dichloro-cis-2,3-diarylcyclopropane (AII)) at 10
–6 mol/l for 4 days, and then treated with EGF (10–10 mol/l) immediately prior to TLVM. EGF enhanced the motility of the MCF-7 cells at 30–90 min post-administration. However, EGF-mediated motility of the MCF-7 cells was inhibited by antiestrogen pretreatment, with TAM and ICI producing complete inhibition of EGF-induced motility. In conclusion, this study demonstrates that EGF enhances the rate of movement of MCF-7 breast cancer cells and that antiestrogen pretreatment inhibits EGF-mediated motility. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]- Published
- 2007
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11. Physicochemical, functional and emulsion properties of edible protein from avocado (Persea americana Mill.) oil processing by-products.
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Wang, Jia-Shui, Wang, An-Bang, Zang, Xiao-Ping, Tan, Lin, Xu, Bi-Yu, Chen, Hai-Hong, Jin, Zhi-Qiang, and Ma, Wei-Hong
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AVOCADO , *TROPICAL fruit , *ESSENTIAL amino acids , *WASTE products , *SOY proteins , *EMULSIONS - Abstract
Graphical abstract Highlights • Edible protein was prepared from avocado oil processing by-products. • Physicochemical and functional properties of avocado protein were investigated. • Oil-in-water emulsions stabilized by avocado protein. • Avocado oil processing by-products is a sustainable protein resource. Abstract Avocado (Persea americana) is a tropical fruit that has drawn great interest its oil for foods and cosmetic industries; however, avocado oil processing by-product is a potential source of edible protein. Herein, edible protein was prepared from defatted avocado meal, and it's physicochemical, functional and emulsion properties were investigated. The avocado protein showed U-shaped exhibiting strong effect of pH, and a minimum solubility being observed at pH 4.5, confirming the isoelectric point of avocado protein. Nutritionally, the avocado protein contains all the essential amino acids. Avocado protein provided higher water and oil absorption capacities, higher radical scavenging capacity but lower in-vitro digestibility compared with soy protein. Furthermore, the avocado protein as emulsifier afforded a stability oil-in-water emulsion system, resulting in a greater emulsifying stability than that of soy protein. The present results highlight the potential source of edible protein from avocado oil processing by-products for functional food ingredients. [ABSTRACT FROM AUTHOR]
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- 2019
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12. 281-P: Purification and characterization of soluble HLA class II
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Skaley, Matthew S., Zang, Xiao-ping, Bardet, Wilfried, Fogle, Matt, and Hildebrand, William H.
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- 2009
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13. 194-P: Characterization of secreted single class II HLA-DR & -DQ molecules
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Zang, Xiao-Ping, Eckerd, Annette, Cate, Steven, Buchli, Rico, and Hildebrand, William
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- 2009
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14. 133-P: Characterization of cells expressing single class II HLA-DR & -DQ alleles
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Zang, Xiao-Ping, Mojsilovi, Danijela, Tian, Runying, Cate, Steven, Buchli, Rico, and Hildebrand, William
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- 2008
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15. Comparison of physicochemical properties and in vitro digestibility of starches from seven banana cultivars in China.
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Wang, Jia-Shui, Wang, An-Bang, Ma, Wei-Hong, Xu, Bi-Yu, Zang, Xiao-Ping, Tan, Lin, Jin, Zhi-Qiang, and Li, Jing-Yang
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SPHEROIDAL state , *POLYGONALES , *DIFFERENTIAL scanning calorimetry , *CALORIMETRY , *FOOD industry - Abstract
Abstract Lots of bananas were wasted before commercialization. It is necessary to search potential industrial applications of banana. In the present study, starches from seven banana cultivars (labeled as A–G) were isolated and then characterized. These starches presented different and irregular shapes, such as sphere, long spheroid and polygonal granules. The distribution of size and analyses of average molecular weight showed more small granules in samples B, D, F and G than other samples. The amylose content varied from 22.59% to 38.40%. The crystal types of these starches were a mixture of B-type and C-type, and the relative crystallinity varied greatly. The differential scanning calorimetry (DSC) results showed that the onset temperature of gelatinization increased as follows: A < B < E < C ≈ D < F. The maximum viscosity of banana starch decreased as follows: G > C > D > F > E = B > A. The in vitro digestibility test showed that the content of resistant starch was very high in banana starches. These results would be useful to the application of those starches in food and nonfood industries. [ABSTRACT FROM AUTHOR]
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- 2019
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16. Influence of novel KGFR tyrosine kinase inhibitors on KGF-mediated proliferation of breast cancer.
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Mehta M, Kesinger JW, Zang XP, Lerner ML, Brackett DJ, Brueggemeier RW, Li PK, and Pento JT
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- Breast Neoplasms pathology, Cell Growth Processes drug effects, Cell Growth Processes physiology, Cell Line, Tumor, Extracellular Signal-Regulated MAP Kinases metabolism, Female, Fibroblast Growth Factor 7 pharmacology, Humans, Indoles pharmacology, MAP Kinase Signaling System drug effects, Quinolones pharmacology, Receptor, Fibroblast Growth Factor, Type 2 metabolism, Breast Neoplasms drug therapy, Breast Neoplasms enzymology, Fibroblast Growth Factor 7 antagonists & inhibitors, Protein Kinase Inhibitors pharmacology, Receptor, Fibroblast Growth Factor, Type 2 antagonists & inhibitors
- Abstract
Background: Keratinocyte growth factor (KGF) acts at the KGF receptor (KGFR) to produce a rapid stimulation of breast cancer cell proliferation and motility which is mediated via the Erk signaling pathway. Enhancement of KGF/KGFR signal transduction may be an early step in the metastatic progression of breast cancer. Receptor modeling of KGFR was used to identify selective KGFR tyrosine kinase (TK) inhibitor molecules that have the potential to bind selectively to the KGFR. The present study evaluated the biological activity of 57 of these KGFR TK inhibitor compounds on breast cancer cells., Materials and Methods: These compounds were tested for their ability to inhibit KGF-mediated breast cancer cell proliferation in MCF-7 breast cancer cells. Furthermore, the effects of the most effective proliferation inhibitors were examined on Erk signaling and on the relative density of cell membrane KGFR., Results: It was observed that 27 of the 57 compounds tested produced a 20% or greater reduction in KGF-mediated proliferation; while five compounds produced greater than 50% inhibition. In addition, the most potent inhibitors also reduced Erk signaling and cell membrane density of the KGFR., Conclusion: The compounds examined appear to be selective KGFR inhibitors which inhibit KGF-mediated activity and reduce the expression of KGFR on cancer cells. These results may lead to the development of a novel class of anticancer agents for the prevention of metastatic cancer progression.
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- 2010
17. Influence of KGF on the progression of pancreatic cancer.
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Zang XP, Lerner M, Brackett D, and Pento JT
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- Cell Adhesion, Humans, Immunoenzyme Techniques, Pancreatic Neoplasms metabolism, Receptor, Fibroblast Growth Factor, Type 2 metabolism, Tumor Cells, Cultured, Cell Movement, Cell Proliferation, Fibroblast Growth Factor 7 pharmacology, Pancreatic Neoplasms pathology
- Abstract
Background: Keratinocyte growth factor (KGF increases the proliferation and motility of many epithelial cells and is known to be up-regulated in pancreatic cancer. The present study examined the hypothesis that KGF may initiate or enhance the progression of pancreatic cancer by increasing the proliferation and motility of pancreatic cancer cells., Materials and Methods: HPAF-II pancreatic cancer cell migration and proliferation was evaluated using a culture wounding assay 24 and 48 hours following KGF treatment. KGF receptor (KGFR) localization in these cells was established by immunohistochemistry., Results: KGF treatment significantly increased the proliferation and motility of the HPAF-II cells. In addition, KGF enhanced the motile morphology of these cancer cells., Conclusion: The results of this study indicate that KGF has a rapid influence on the proliferation and motility of HPAF-II cells and suggest that KGF may be involved in the progression of pancreatic cancer.
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- 2009
18. Selective growth inhibition of cancer cells by L-methioninase-containing fusion protein targeted to the urokinase receptor.
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Palwai NR, Zang XP, Harrison RG, Benbrook D, and Pento JT
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- Cell Line, Tumor, Cell Movement drug effects, Cell Survival drug effects, Dose-Response Relationship, Drug, Drug Delivery Systems, Humans, Mutation, Recombinant Fusion Proteins genetics, Antineoplastic Agents pharmacology, Carbon-Sulfur Lyases genetics, Cell Proliferation drug effects, Receptors, Urokinase Plasminogen Activator metabolism, Recombinant Fusion Proteins pharmacology
- Abstract
Background: We have reported the development of a novel fusion protein (FP) consisting of an amino-terminal fragment of urokinase linked to the amino terminus of the enzyme L-methioninase (L-M). The present study compared the effect of this novel FP on the proliferation of human ovarian, skin, breast endometrial and pancreatic cancer cell lines., Methods: The FP, L-M and a mutated FP, with reduced L-M activity, were produced by recombinant methods. The effect of treatment with FP, L-M and mutated FP on the proliferation of the cancer cells was measured in vitro using an MTS assay., Results: The inhibitory effect of the FP was found to be significantly greater than that of L-M alone or the mutated FP. In addition, the FP produced a greater inhibitory effect on an ovarian cancer cell line than on comparable normal, non-cancerous cells. Further, the FP produced a dose-dependent inhibition of the proliferation of pancreatic cancer cell lines., Conclusion: These results suggest that this FP is a potent and selective inhibitor of the proliferation of various cancer cell lines and has potential as a therapeutic agent for the treatment of various methionine-dependent cancers., (Copyright 2009 S. Karger AG, Basel.)
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- 2009
- Full Text
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19. SiRNA inhibition of ER-alpha expression reduces KGF-induced proliferation of breast cancer cells.
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Zang XP and Pento JT
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- Breast Neoplasms metabolism, Breast Neoplasms pathology, Cell Growth Processes drug effects, Cell Growth Processes genetics, Cell Line, Tumor, Estrogen Receptor alpha biosynthesis, Estrogen Receptor alpha genetics, Fibroblast Growth Factor 7 antagonists & inhibitors, Humans, Transfection, Breast Neoplasms genetics, Estrogen Receptor alpha antagonists & inhibitors, Fibroblast Growth Factor 7 pharmacology, RNA, Small Interfering genetics
- Abstract
Background: Keratinocyte growth factor (KGF) produces a rapid increase in the proliferation and motility of estrogen receptor (ER)-positive breast cancer cells which is abolished by estrogen deprivation and/or anti-estrogen treatment. The present study examined the hypothesis that ER-alpha is involved in the KGF proliferation in MCF-7 cancer cells using small interfering RNA (siRNA) to selectively inhibit ER-alpha expression., Materials and Methods: At 48 hours following ER-alpha siRNA transfection, the MCF-7 cells were treated with KGF (50 ng/ml) or vehicle for 24 hours. Cell proliferation was measured using a MTT assay. ER-alpha protein levels were quantified by Western blotting., Results: ER-alpha siRNA transfection significantly reduced ER-alpha expression and MCF-7 cell proliferation. KGF-mediated enhancement of cell proliferation and motile cell morphology were reduced or absent in the siRNA transfected MCF-7 cells., Conclusion: ER-alpha expression is associated with KGF-induced proliferation of breast cancer cells.
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- 2008
20. Wilms' tumor 1 protein and focal adhesion kinase mediate keratinocyte growth factor signaling in breast cancer cells.
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Zang XP, Pento JT, and Tari AM
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- Breast Neoplasms enzymology, Breast Neoplasms pathology, Cell Cycle Proteins, Cell Line, Tumor, Cell Movement physiology, Down-Regulation, Enzyme Activation, Fibroblast Growth Factor 7 antagonists & inhibitors, Fibroblast Growth Factor 7 pharmacology, Focal Adhesion Protein-Tyrosine Kinases biosynthesis, GRB2 Adaptor Protein biosynthesis, Humans, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Nuclear Proteins biosynthesis, Phosphorylation, RNA Splicing Factors, Recombinant Proteins pharmacology, Signal Transduction, Breast Neoplasms metabolism, Fibroblast Growth Factor 7 metabolism, Focal Adhesion Protein-Tyrosine Kinases metabolism, Nuclear Proteins metabolism
- Abstract
Background: Keratinocyte growth factor (KGF) has been shown to induce breast cancer metastasis in animal models. cDNA microarrays have revealed that KGF increased Wilms tumor 1 (WT1) and focal adhesion kinase (FAK) expression in breast cancer cells. The role of WT1 and FAK in KGF signaling was investigated., Materials and Methods: A cell culture wounding model was used to study the effects of WT1 and FAK down-regulation on KGF-induced proliferation and motility in breast cancer cells., Results: WT1 down-regulation inhibited KGF-mediated proliferation and motility of breast cancer cells, while FAK down-regulation inhibited proliferation, but had no significant effect on cell motility. WT1 down-regulation, but not FAK down-regulation, led to Erk1,2 inactivation., Conclusion: KGF-mediated signaling employs WT1 and FAK to regulate breast cancer cell proliferation and motility and may represent therapeutic targets for the prevention of breast cancer progression.
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- 2008
21. Development of keratinocyte growth factor receptor tyrosine kinase inhibitors for the treatment of cancer.
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Hackett J, Xiao Z, Zang XP, Lerner ML, Brackett DJ, Brueggemeier RW, Li PK, and Pento JT
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- Breast Neoplasms enzymology, Breast Neoplasms pathology, Cell Growth Processes drug effects, Cell Line, Tumor, Cell Movement drug effects, Drug Design, Humans, Immunohistochemistry, Quinolones chemical synthesis, Quinolones pharmacology, Breast Neoplasms drug therapy, Protein Kinase Inhibitors chemical synthesis, Protein Kinase Inhibitors pharmacology, Receptor, Fibroblast Growth Factor, Type 2 antagonists & inhibitors
- Abstract
Background: The mammary glands of adult female animals are remarkably sensitive to keratinocyte growth factor (KGF). KGF acts at the KGF receptor (KGFR) to produce a rapid and profound stimulation of breast cancer cell proliferation and motility. Further, KGF-induced motility in breast cancer cells is mediated via the Erk1/2 signaling pathway. Thus, enhancement of KGF/KGFR signal transduction may be an early step in the metastatic progression of breast cancer. Receptor modeling of KGFR was used to identify selective KGFR tyrosine kinase inhibitor (TKI) molecules with high receptor affinity. The present study describes the synthesis and biological activity of three of the KGFR TKI compounds., Materials and Methods: Computer modeling of the KGFR was used to create a virtual library of compounds that have the potential to bind with high affinity to the KGFR. Three of these compounds were synthesized and tested in this study. The compounds were tested for their ability to inhibit KGF-mediated breast cancer cell proliferation and motility using a culture wounding assay. In addition, the effect of the most potent KGFR TKI compound on the relative density of cell membrane KGFR was measured using immunocytochemistry., Results: It was observed that the KGFR TKIs decreased KGF-mediated activity as predicted by computer modeling. In addition, the most potent inhibitor also reduced the density of the KGFR on the membrane of the cancer cells., Conclusion: The novel inhibitors identified in this project are selective KGFR inhibitors which appear to reduce the expression of KGFR on cancer cells. These results may lead to the development of a novel class of anticancer agents for the chemoprevention of metastatic cancer development and provide a new approach in the treatment of breast cancer.
- Published
- 2007
22. Influence of L-methioninase targeted to the urokinase receptor on the proliferation and motility of lung and prostate cancer cells.
- Author
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Palwai NR, Zang XP, Harrison RG, and Pento JT
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- Carbon-Sulfur Lyases genetics, Cell Growth Processes drug effects, Cell Growth Processes physiology, Cell Line, Tumor, Cell Movement drug effects, Cell Movement physiology, Drug Delivery Systems, Humans, Lung Neoplasms metabolism, Male, Mutation, Peptide Fragments genetics, Peptide Fragments pharmacology, Prostatic Neoplasms metabolism, Receptors, Cell Surface genetics, Receptors, Urokinase Plasminogen Activator, Recombinant Fusion Proteins genetics, Carbon-Sulfur Lyases pharmacology, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Prostatic Neoplasms drug therapy, Prostatic Neoplasms pathology, Receptors, Cell Surface metabolism, Recombinant Fusion Proteins pharmacology
- Abstract
Background: Previously, we reported that a novel fusion protein consisting of an amino-terminal fragment of urokinase linked to the amino terminus of the enzyme L-methioninase inhibited MCF-7 breast cancer cells in vitro to a greater extent than treatment with L-methioninase., Materials and Methods: The fusion protein, L-methioninase and a mutated fusion protein without L-methioninase activity were produced by recombinant methods. The effects of fusion protein, L-methioninase, and mutated fusion protein treatment on the proliferation and motility of SK-LU-i lung and PC-3 prostate and cancer cells were measured in vitro using a culture wounding assay., Results: The fusion protein produced a dose-dependent inhibition of the proliferation and motility of both cancer cell lines. In addition, the fusion protein was found to be significantly more effective than L-methioninase alone or mutated fusion protein., Conclusion: Our results suggest that this fusion protein has potential as a selective therapeutic agent for the treatment of various methionine-dependent cancers.
- Published
- 2007
23. A Comparison of KGF Receptor Expression in Various Types of Human Cancer.
- Author
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Zang XP, Lerner MR, Bahr SJ, Brackett DJ, and Pento JT
- Abstract
Background: Keratinocyte growth factor (KGF) has been observed to produce a rapid increase in the motility of breast cancer cells. KGF/KGFR (KGF receptor) signaling has also been demonstrated in the progression of many types of human cancer. The objective of the present study was to compare KGFR expression in various types of cancer., Materials and Methods: A cancer profiling array containing cDNA from 154 tumor and paired normal samples representing 19 types of human cancer was employed., Results: The results of the present study indicate that KGFR expression is enhanced in many types of human carcinomas at an early stage of cancer development, suggesting that KGFR overexpression may be an early signal in the progression of these cancers. However, the stage of cancer progression and relative level of expression varied considerably among the various types of cancer., Conclusion: These findings suggest that tumor KGFR levels may serve as a prognostic biomarker for cancer staging and/or treatment., (Copyright© 2006 International Institute of Anticaner Research (Dr. John G. Delinassios), All rights reserved.)
- Published
- 2006
24. Targeting a methioninase-containing fusion protein to breast cancer urokinase receptors inhibits growth and migration.
- Author
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Zang XP, Palwai NR, Lerner MR, Brackett DJ, Pento JT, and Harrison RG
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- Animals, Breast Neoplasms pathology, Carbon-Sulfur Lyases genetics, Cell Growth Processes drug effects, Cell Line, Tumor, Cell Movement drug effects, Humans, Injections, Intralesional, Mice, Mice, Nude, Mutagenesis, Site-Directed, Receptors, Cell Surface genetics, Receptors, Urokinase Plasminogen Activator, Recombinant Fusion Proteins biosynthesis, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Xenograft Model Antitumor Assays, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Carbon-Sulfur Lyases administration & dosage, Receptors, Cell Surface metabolism, Recombinant Fusion Proteins administration & dosage
- Abstract
Background: We previously reported that a novel fusion protein (consisting of an amino-terminal fragment of urokinase which binds to the urokinase receptor, and L-methioninase which depletes methionine and arrests the growth of methionine-dependent tumors) inhibited MCF-7 breast cancer cells in vitro., Materials and Methods: We produced this fusion protein, L-methioninase, and a mutated fusion protein without L-methioninase activity by recombinant methods. MCF-7 cell proliferation and mobility were measured in vitro in a culture wounding assay. Protein binding to MCF-7 cells was measured by immunocytochemical localization. MCF-7 tumor xenograft growth was measured in nude mice., Results: The fusion protein was significantly more effective than L-methioninase in either the in vitro or in vivo assays. The binding assay showed that the unmutated and mutated fusion protein bound to the cells, but L-methioninase did not., Conclusion: Our results suggest that this fusion protein has potential as a therapeutic agent for cancer treatment.
- Published
- 2006
25. Enhanced motility of KGF-transfected breast cancer cells.
- Author
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Zang XP, Bullen EC, Manjeshwar S, Jupe ER, Howard EW, and Pento JT
- Subjects
- Animals, Breast Neoplasms genetics, Breast Neoplasms metabolism, Cell Line, Tumor, Fibroblast Growth Factor 7 biosynthesis, Fibroblast Growth Factor 7 genetics, Fibroblast Growth Factor 7 metabolism, Humans, Mice, Mice, Nude, Neoplasm Transplantation, Transfection, Transplantation, Heterologous, Breast Neoplasms pathology, Cell Movement physiology, Fibroblast Growth Factor 7 physiology
- Abstract
Background: In a previous study, we reported that keratinocyte growth factor (KGF) produced a rapid increase in the motility of ER-positive breast cancer cells. Others have demonstrated that KGF treatment in rodent species produces rapid mammary ductal hyperplasia. Epithelial cells do not produce KGF; thus, in the present study, MCF-7 cells were stably transfected with a KGF-expressing vector and the motility and morphology of the transfected, non-transfected and empty vector cell lines compared., Materials and Methods: A mammalian expression vector containing a KGF cDNA was transfected into MCF-7/beta cells, and two stable clones (MCF-7/beta/KGF-T8 and MCF-7/beta/KGF-T9) were identified. Western blotting of conditioned medium from these clones was used to confirm the expression of KGF. The motility of wild-type and KGF-transfected MCF-7 cells was compared using time-lapse videomicroscopy and a cell culture wounding model which examined cell migration over a period of 1-3 days., Results: The Western blots demonstrated that the expression of KGF in both the MCF-7/beta/KGF-T8 and MCF-7/beta/KGF-T9 cell lines was higher than the wild-type and MCF-7/beta cell lines. The cell proliferation and migration distance was significantly greater for both KGF-transfected MCF-7 cell lines than the wild-type and MCF-7/beta cell lines under the same experimental conditions. Further, changes in motile morphology were observed in both the MCF-7/beta/KGF-T8 and MCF-7/beta/KGF-T9 cell lines. In addition, the MCF-7/beta/KGF-T8 clone was found to produce much larger tumors than both the MCF-7/beta/KGF-T9 and EV clones in mouse xenografts. These results indicated that autocrine production of KGF in the KGF-transfected MCF-7 cell lines enhanced cell migration, migration-related morphology and xenograft tumor growth., Conclusion: KGF-transfected MCF-7 cells displayed a much greater motility than non-transfected cells, confirming the KGF motility enhancement effect which we previously reported. The use of KGF-transfected breast cancer cells in the xenograft model may help to study the mechanism of KGF-mediated cell motility and to identify specific KGF antagonists that may be used to prevent or impede KGF-mediated metastatic progression.
- Published
- 2006
26. Keratinocyte Growth Factor-Mediated Pattern of Gene Expression in Breast Cancer Cells.
- Author
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Zang XP, Lerner ML, DO SV, Brackett DJ, and Pento JT
- Abstract
Background: Breast cancer metastasis is associated with the motility and invasiveness of breast cancer cells. In a previous study we reported the motility enhancement effect of keratinocyte growth factor (KGF) on breast cancer cells. This study established and characterized the influence of KGF on breast cancer cell motility and determined that KGF-induced motility was observed only in estrogen receptor-positive breast cancer cells. The objective of the present study was to identify genes involved in the KGF motility response in human breast cancer cells., Materials and Methods: Using cDNA expression assays, we compared the expression of mRNA in control and KGF-treated MCF-7 breast cancer cells. Scatter plots and cluster analysis of gene expression were used to determine KGF-mediated gene expression patterns., Results: It was determined that over 100 genes were up- or down-regulated from 3-100 fold at 1h following KGF treatment. We identified up-regulated and down-regulated target genes that are associated with some aspect of tumor progression, proliferation or metastasis., Conclusion: Knowledge of specific genes and patterns of gene regulation associated with KGF-enhanced cell motility may provide important new information concerning the mechanisms involved in tumor metastasis. In addition, these genes and/or protein products may serve as novel therapeutic targets or biomarkers of metastatic progression. The pattern gene of expression observed in this study provides new information on the molecular signature associated with the motility and metastatic progression of breast cancer., (Copyright© 2004 International Institute of Anticaner Research (Dr. John G. Delinassios), All rights reserved.)
- Published
- 2004
27. Antisense KGFR oligonucleotide inhibition of KGF-induced motility in breast cancer cells.
- Author
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Zang XP, Lerner MR, Dunn ST, Brackett DJ, and Pento JT
- Subjects
- Base Sequence, Breast Neoplasms pathology, Cell Movement drug effects, Female, Fibroblast Growth Factor 7, Gene Expression Regulation, Neoplastic drug effects, Humans, Kinetics, Neoplasm Metastasis prevention & control, Polymerase Chain Reaction, Receptor, Fibroblast Growth Factor, Type 2, Tumor Cells, Cultured, Breast Neoplasms physiopathology, Cell Movement physiology, Fibroblast Growth Factors physiology, Oligonucleotides, Antisense pharmacology, Receptors, Fibroblast Growth Factor genetics
- Abstract
Background: The metastasis of breast cancer is known to be directly associated with the motility of breast cancer cells. We have previously shown that keratinocyte growth factor (KGF) enhances the motility of estrogen receptor (ER)-positive breast cancer cells and that this motility response is associated with cellular levels of the KGF receptor (KGFR). Further, we observed that KGF treatment enhanced KGFR gene expression in MCF-7 cells. The objective of the present study was to examine the influence of antisense KGFR oligonucleotide treatment on the KGF-induced motility response in breast cancer cells., Materials and Methods: Both time-lapse video microscopy (TLVM) and culture wounding experiments were used to quantify cell motility. KGFR antisense effects on the expression of KGFR were determined by Western blotting, real time PCR and immunocytochemistry., Results: Antisense KGFR treatment significantly reduced both KGFR mRNA and protein expression. In addition, the antisense KGFR abolished the KGF-mediated cell motility response as early as 2 h following KGF treatment as observed by TLVM and lasting for up 48 h as observed by culture wounding. CONCLUSIOS: The results of this study indicate that KGFR activation and intracellular signaling mediates the KGF motility effect and suggests that KGFR may be an important new therapeutic target for the treatment or prevention of metastatic progression in breast cancer.
- Published
- 2003
28. Specific and non-specific KGF inhibition of KGF-induced breast cancer cell motility.
- Author
-
Zang XP, Nguyen TN, and Pento JT
- Subjects
- Cell Division drug effects, Cell Division physiology, Cell Movement physiology, Dose-Response Relationship, Drug, Fibroblast Growth Factor 7, Fibroblast Growth Factors pharmacology, Heparin pharmacology, Heparin, Low-Molecular-Weight pharmacology, Immunoglobulin Fc Fragments pharmacology, Microscopy, Video, Peptide Fragments pharmacology, Receptor, Fibroblast Growth Factor, Type 2, Receptors, Fibroblast Growth Factor chemistry, Recombinant Fusion Proteins pharmacology, Recombinant Proteins antagonists & inhibitors, Recombinant Proteins pharmacology, Substrate Specificity, Tumor Cells, Cultured, Breast Neoplasms pathology, Cell Movement drug effects, Fibroblast Growth Factors antagonists & inhibitors
- Abstract
Background: Keratinocyte growth factor (KGF), a member of the fibroblast growth factor family, is a mesenchymally derived mediator of epithelial cell proliferation and migration. In a previous study, we reported that KGF enhanced the motility of human breast cancer cells. The objective of the present study was to examine the influence of specific and non-specific KGF inhibitors on KGF-induced motility and proliferation in ER-positive MCF-7 cells., Materials and Methods: In the present study three KGF inhibitors were employed [Heparin, Innohep, a low molecular weight heparin (LMWH) and KGFR2 beta (IIIb)/Fc, a chimeric KGFR fragment]. Heparin and LMWH bind to low affinity sites on KGF and produce non-specific inhibition, while KGFR2 beta (IIIb)/Fc, a soluble chimera of an extracellular KGFR fragment, is a more specific KGF inhibitor. Cellular motility was measured using two methods: culture wounding over a period of 48 hours; and secondly, time-lapse videomicroscopy (TLVM)., Results: In these experiments KGF was found to produce a dose-dependent enhancement of MCF-7 cell motility over a dosage range of 5 to 500 ng/ml. In the TLVM experiments, Heparin (30 ng/ml), LMWH (30 ng/ml) and KGFR2 beta (IIIb)/Fc (50 micrograms/ml) completely inhibited KGF-induced motility of MCF-7 cells during the initial 2-hour observation period. In the culture wounding assay, LMWH produced a greater reduction in KGF-induced motility than heparin at 48 hours post-treatment., Conclusion: The results of this study indicate that KGF-mediated enhancement of breast cancer cells motility and proliferation is inhibited by both specific and non-specific KGF inhibitors. LMWH appears to produce an inhibition of KGF with a much longer duration of action than Heparin. Our results suggest that KGF inhibition may be a potential new therapeutic approach for the treatment of metastatic breast cancer.
- Published
- 2002
29. The effect of antiestrogens on TGF-beta-mediated chemotaxis of human breast cancer cells.
- Author
-
Tong GM, Rajah TT, Zang XP, and Pento JT
- Subjects
- Breast Neoplasms drug therapy, Collagenases metabolism, Estradiol pharmacology, Fulvestrant, Humans, Receptors, Transforming Growth Factor beta biosynthesis, Tamoxifen pharmacology, Transforming Growth Factor beta pharmacology, Tumor Cells, Cultured, Antineoplastic Agents pharmacology, Breast Neoplasms pathology, Chemotaxis drug effects, Estradiol analogs & derivatives, Estrogen Receptor Modulators pharmacology, Tamoxifen analogs & derivatives, Transforming Growth Factor beta antagonists & inhibitors
- Abstract
Background: In a previous study we compared the influence of several growth factors on cancer cells in culture and observed that transforming growth factor-beta (TGF-beta) enhanced the invasiveness of several breast cancer cell lines. The objective of the present study was to determine the influence of three unique antiestrogens on TGF-beta-mediated chemotaxis of human breast cancer cells., Materials and Methods: The chemotactic activity of TGF-beta was assayed in vitro using collagen IV-coated transwell chambers with either MCF-7 or MDA-MB-231 human breast cancer cells. The cells were pretreated with antiestrogen for 4 days, harvested and placed in the upper transwell chamber. TGF-beta was added to the lower chamber and cell migration and collagenase release were determined following a 6-hour incubation., Results: In this study TGF-beta enhanced the chemotaxis of both cell types with a much greater effect on the MDA-MB-231 cells. However, TGF-beta-mediated chemotaxis of the MCF-7 cells was inhibited by antiestrogen pretreatment while TGF-beta-mediated chemotaxis of the MDA-MB-231 cells was not altered. Further, neither TGF-beta nor antiestrogen treatment altered collagenase release from either cell line., Conclusion: The data demonstrate that pure antiestrogens are capable of inhibiting TGF-beta-mediated chemotaxis in estrogen receptor (ER)-positive breast cancer cells by a mechanism which is independent of collagenase release. Finally, the results of this study suggest a coupling of the TGF-beta and ER signaling pathways and indicate that TGF-beta may be an important therapeutic target for the treatment or inhibition of breast cancer metastasis.
- Published
- 2002
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