The Experts below are selected from a list of 268017 Experts worldwide ranked by ideXlab platform
Raimon Duranstruuck - One of the best experts on this subject based on the ideXlab platform.
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development of a transplantable gfp b cell lymphoma Tumor cell line from mhc defined miniature swine potential for a large animal Tumor Model
Frontiers in Oncology, 2019Co-Authors: Marian Schenk, Abraham J Matar, Isabel Hanekamp, Robert J Hawley, Christene A Huang, Raimon DuranstruuckAbstract:The lack of a reliable and reproducible large animal Tumor Model for the study of hemolymphatic malignancies limits the ability to explore the underlying pathophysiology and testing of novel therapies. The goal of this study was to develop an aggressive, trackable swine Tumor cell line in mice for adoptive transfer into MHC matched swine. Two Tumor cell lines, post-transplant lymphoproliferative disease (PTLD) 13271 and chronic myelogenous leukemia (CML) 14736, were previously established from the Massachusetts General Hospital (MGH) miniature swine herd. PTLD 13271 is a swine B-cell lymphoma line originating from an animal that developed PTLD following hematopoietic cell transplantation (HCT), while CML 14736 was generated from a swine that spontaneously developed CML. In order to select for aggressive Tumor variants, both lines were passage into NOD/SCID IL-2 receptor γ−/− (NSG) mice. Tumor induced mortality in mice injected with {"type":"entrez-protein","attrs":{"text":"CML14736","term_id":"888610597","term_text":"CML14736"}}CML14736 was 68% while 100% of mice injected with PTLD 13271 succumbed to PTLD by day 70. Based on aggressiveness, PTLD 13271 was selected for further development and re-passage into NSG mice resulting in increased Tumor burden and metastasis. Transduction of the PTLD 13271 cell line with a green fluorescent protein (GFP)-expressing lentivirus facilitated Tumor tracking when re-passaged in mice. Utilizing a tolerance induction strategy, GFP+ Tumors were injected into an MHC matched miniature swine and successfully followed via flow cytometry for 48 h in circulation, although Tumor engraftment was not observed. In summary, we report the development of an aggressive GFP+B-cell lymphoma cell line which has the potential for facilitating development of a large animal Tumor Model.
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myeloid leukemias and virally induced lymphomas in miniature inbred swine development of a large animal Tumor Model
Frontiers in Genetics, 2015Co-Authors: Raimon Duranstruuck, Abraham J Matar, Christene A HuangAbstract:The lack of a large animal transplantable Tumor Model has limited the study of novel therapeutic strategies for the treatment of liquid cancers. Swine as a species provide a natural option based on their similarities with humans and their already extensive use in biomedical research. Specifically, the MGH miniature swine herd retains unique genetic characteristics that facilitate the study of hematopoietic cell and solid organ transplantation. Spontaneously arising liquid cancers in these swine, specifically myeloid leukemias and B cell lymphomas, closely resemble human malignancies. The ability to establish aggressive Tumor cell lines in vitro from these naturally occurring malignancies makes a transplantable Tumor Model a close reality. Here, we discuss our experience with myeloid and lymphoid Tumors in MHC characterized miniature swine and future approaches regarding the development of a large animal transplantable Tumor Model.
Martin E Gleave - One of the best experts on this subject based on the ideXlab platform.
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synergistic chemosensitization and inhibition of progression to androgen independence by antisense bcl 2 oligodeoxynucleotide and paclitaxel in the lncap prostate Tumor Model
International Journal of Cancer, 2001Co-Authors: Simon Leung, Hideaki Miyake, Tobias Zellweger, Anthony W Tolcher, Martin E GleaveAbstract:Bcl-2 expression is up-regulated in prostate cancer cells after androgen ablation and associated with development of androgen independence and chemoresistance. We recently reported that antisense Bcl-2 oligodeoxynucleotides (ODNs) delay progression to androgen independence in the androgen-dependent (AD) human LNCaP prostate Tumor Model. The objectives in this study were to determine whether antisense human Bcl-2 ODN enhances chemosensitivity of paclitaxel and whether combined antisense Bcl-2 ODN and paclitaxel further delays time to androgen-independent (AI) progression in the LNCaP Tumor Model. Semi-quantitative reverse transcriptast-polymerase chain reaction revealed that treatment of LNCaP cells with antisense Bcl-2 ODN decreased Bcl-2 expression in a dose-dependent and sequence-specific manner, whereas Bcl-2 expression was not affected by paclitaxel treatment. Antisense Bcl-2 ODN treatment significantly enhanced paclitaxel chemosensitivity in vitro, reducing cell viability after treatment with 1 nM paclitaxel from 76% to 42%. Characteristic apoptotic DNA laddering was demonstrated after combined treatment with 500 nM antisense Bcl-2 ODN and 1 nM paclitaxel but not with either agent alone. Adjuvant in vivo administration of combined antisense Bcl-2 and polymeric micellar paclitaxel after castration resulted in a significant delay of emergence of AI recurrent LNCaP Tumors compared with either agent alone. By 15 weeks post castration, Tumor volume in mice treated with antisense Bcl-2 ODN alone or mismatch control ODN plus paclitaxel was >3-fold higher than in mice treated with combined antisense Bcl-2 ODN and paclitaxel. Mean serum prostate-specific antigen levels returned to or were above precastration levels by 11 weeks post castration in mice treated with antisense Bcl-2 ODN alone or mismatch control ODN plus paclitaxel but remained 90% below the pre-castration level in mice treated with combined antisense Bcl-2 ODN and paclitaxel. These findings identify combined antisense Bcl-2 and paclitaxel as a potentially new therapeutic strategy for advanced prostate cancer by enhancing paclitaxel chemosensitivity and delaying progression of hormone-refractory prostate cancer. © 2001 Wiley-Liss, Inc.
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synergistic chemosensitization and inhibition of progression to androgen independence by antisense bcl 2 oligodeoxynucleotide and paclitaxel in the lncap prostate Tumor Model
International Journal of Cancer, 2001Co-Authors: Simon Leung, Hideaki Miyake, Tobias Zellweger, Anthony W Tolcher, Martin E GleaveAbstract:Bcl-2 expression is up-regulated in prostate cancer cells after androgen ablation and associated with development of androgen independence and chemoresistance. We recently reported that antisense Bcl-2 oligodeoxynucleotides (ODNs) delay progression to androgen independence in the androgen-dependent (AD) human LNCaP prostate Tumor Model. The objectives in this study were to determine whether antisense human Bcl-2 ODN enhances chemosensitivity of paclitaxel and whether combined antisense Bcl-2 ODN and paclitaxel further delays time to androgen-independent (AI) progression in the LNCaP Tumor Model. Semi-quantitative reverse transcriptast-polymerase chain reaction revealed that treatment of LNCaP cells with antisense Bcl-2 ODN decreased Bcl-2 expression in a dose-dependent and sequence-specific manner, whereas Bcl-2 expression was not affected by paclitaxel treatment. Antisense Bcl-2 ODN treatment significantly enhanced paclitaxel chemosensitivity in vitro, reducing cell viability after treatment with 1 nM paclitaxel from 76% to 42%. Characteristic apoptotic DNA laddering was demonstrated after combined treatment with 500 nM antisense Bcl-2 ODN and 1 nM paclitaxel but not with either agent alone. Adjuvant in vivo administration of combined antisense Bcl-2 and polymeric micellar paclitaxel after castration resulted in a significant delay of emergence of AI recurrent LNCaP Tumors compared with either agent alone. By 15 weeks post castration, Tumor volume in mice treated with antisense Bcl-2 ODN alone or mismatch control ODN plus paclitaxel was >3-fold higher than in mice treated with combined antisense Bcl-2 ODN and paclitaxel. Mean serum prostate-specific antigen levels returned to or were above precastration levels by 11 weeks post castration in mice treated with antisense Bcl-2 ODN alone or mismatch control ODN plus paclitaxel but remained 90% below the pre-castration level in mice treated with combined antisense Bcl-2 ODN and paclitaxel. These findings identify combined antisense Bcl-2 and paclitaxel as a potentially new therapeutic strategy for advanced prostate cancer by enhancing paclitaxel chemosensitivity and delaying progression of hormone-refractory prostate cancer.
Fan Yang - One of the best experts on this subject based on the ideXlab platform.
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Bioengineered 3D brain Tumor Model to elucidate the effects of matrix stiffness on glioblastoma cell behavior using PEG-based hydrogels.
Molecular pharmaceutics, 2014Co-Authors: Christine Wang, Xinming Tong, Fan YangAbstract:Glioblastoma (GBM) is the most common and aggressive form of primary brain Tumor with a median survival of 12-15 months, and the mechanisms underlying GBM Tumor progression remain largely elusive. Given the importance of Tumor niche signaling in driving GBM progression, there is a strong need to develop in vitro Models to facilitate analysis of brain Tumor cell-niche interactions in a physiologically relevant and controllable manner. Here we report the development of a bioengineered 3D brain Tumor Model to help elucidate the effects of matrix stiffness on GBM cell fate using poly(ethylene-glycol) (PEG)-based hydrogels with brain-mimicking biochemical and mechanical properties. We have chosen PEG given its bioinert nature and tunable physical property, and the resulting hydrogels allow tunable matrix stiffness without changing the biochemical contents. To facilitate cell proliferation and migration, CRGDS and a MMP-cleavable peptide were chemically incorporated. Hyaluronic acid (HA) was also incorporated to mimic the concentration in the brain extracellular matrix. Using U87 cells as a Model GBM cell line, we demonstrate that such biomimetic hydrogels support U87 cell growth, spreading, and migration in 3D over the course of 3 weeks in culture. Gene expression analyses showed U87 cells actively deposited extracellular matrix and continued to upregulate matrix reModeling genes. To examine the effects of matrix stiffness on GBM cell fate in 3D, we encapsulated U87 cells in soft (1 kPa) or stiff (26 kPa) hydrogels, which respectively mimics the matrix stiffness of normal brain or GBM Tumor tissues. Our results suggest that changes in matrix stiffness induce differential GBM cell proliferation, morphology, and migration modes in 3D. Increasing matrix stiffness led to delayed U87 cell proliferation inside hydrogels, but cells formed denser spheroids with extended cell protrusions. Cells cultured in stiff hydrogels also showed upregulation of HA synthase 1 and matrix metalloproteinase-1 (MMP-1), while simultaneously downregulating HA synthase 2 and MMP-9. This suggests that varying matrix stiffness can induce differential ECM deposition and reModeling by employing different HA synthases or MMPs. Furthermore, increasing matrix stiffness led to simultaneous upregulation of Hras, RhoA, and ROCK1, suggesting a potential link between the mechanosensing pathways and the observed differential cell responses to changes in matrix stiffness. The bioengineered 3D hydrogel platform reported here may provide a useful 3D in vitro brain Tumor Model for elucidating the mechanisms underlying GBM progression, as well as for evaluating the efficacy of potential drug candidates for treating GBM.
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bioengineered 3d brain Tumor Model to elucidate the effects of matrix stiffness on glioblastoma cell behavior using peg based hydrogels
Molecular Pharmaceutics, 2014Co-Authors: Christine Wang, Xinming Tong, Fan YangAbstract:Glioblastoma (GBM) is the most common and aggressive form of primary brain Tumor with a median survival of 12–15 months, and the mechanisms underlying GBM Tumor progression remain largely elusive. Given the importance of Tumor niche signaling in driving GBM progression, there is a strong need to develop in vitro Models to facilitate analysis of brain Tumor cell-niche interactions in a physiologically relevant and controllable manner. Here we report the development of a bioengineered 3D brain Tumor Model to help elucidate the effects of matrix stiffness on GBM cell fate using poly(ethylene-glycol) (PEG)-based hydrogels with brain-mimicking biochemical and mechanical properties. We have chosen PEG given its bioinert nature and tunable physical property, and the resulting hydrogels allow tunable matrix stiffness without changing the biochemical contents. To facilitate cell proliferation and migration, CRGDS and a MMP-cleavable peptide were chemically incorporated. Hyaluronic acid (HA) was also incorporated t...
Christene A Huang - One of the best experts on this subject based on the ideXlab platform.
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development of a transplantable gfp b cell lymphoma Tumor cell line from mhc defined miniature swine potential for a large animal Tumor Model
Frontiers in Oncology, 2019Co-Authors: Marian Schenk, Abraham J Matar, Isabel Hanekamp, Robert J Hawley, Christene A Huang, Raimon DuranstruuckAbstract:The lack of a reliable and reproducible large animal Tumor Model for the study of hemolymphatic malignancies limits the ability to explore the underlying pathophysiology and testing of novel therapies. The goal of this study was to develop an aggressive, trackable swine Tumor cell line in mice for adoptive transfer into MHC matched swine. Two Tumor cell lines, post-transplant lymphoproliferative disease (PTLD) 13271 and chronic myelogenous leukemia (CML) 14736, were previously established from the Massachusetts General Hospital (MGH) miniature swine herd. PTLD 13271 is a swine B-cell lymphoma line originating from an animal that developed PTLD following hematopoietic cell transplantation (HCT), while CML 14736 was generated from a swine that spontaneously developed CML. In order to select for aggressive Tumor variants, both lines were passage into NOD/SCID IL-2 receptor γ−/− (NSG) mice. Tumor induced mortality in mice injected with {"type":"entrez-protein","attrs":{"text":"CML14736","term_id":"888610597","term_text":"CML14736"}}CML14736 was 68% while 100% of mice injected with PTLD 13271 succumbed to PTLD by day 70. Based on aggressiveness, PTLD 13271 was selected for further development and re-passage into NSG mice resulting in increased Tumor burden and metastasis. Transduction of the PTLD 13271 cell line with a green fluorescent protein (GFP)-expressing lentivirus facilitated Tumor tracking when re-passaged in mice. Utilizing a tolerance induction strategy, GFP+ Tumors were injected into an MHC matched miniature swine and successfully followed via flow cytometry for 48 h in circulation, although Tumor engraftment was not observed. In summary, we report the development of an aggressive GFP+B-cell lymphoma cell line which has the potential for facilitating development of a large animal Tumor Model.
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Development of a Transplantable GFP+ B-Cell Lymphoma Tumor Cell Line From MHC-Defined Miniature Swine: Potential for a Large Animal Tumor Model
Frontiers Media S.A., 2019Co-Authors: Marian Schenk, Abraham J Matar, Isabel Hanekamp, Robert J Hawley, Christene A Huang, Raimon Duran-struuckAbstract:The lack of a reliable and reproducible large animal Tumor Model for the study of hemolymphatic malignancies limits the ability to explore the underlying pathophysiology and testing of novel therapies. The goal of this study was to develop an aggressive, trackable swine Tumor cell line in mice for adoptive transfer into MHC matched swine. Two Tumor cell lines, post-transplant lymphoproliferative disease (PTLD) 13271 and chronic myelogenous leukemia (CML) 14736, were previously established from the Massachusetts General Hospital (MGH) miniature swine herd. PTLD 13271 is a swine B-cell lymphoma line originating from an animal that developed PTLD following hematopoietic cell transplantation (HCT), while CML 14736 was generated from a swine that spontaneously developed CML. In order to select for aggressive Tumor variants, both lines were passage into NOD/SCID IL-2 receptor γ−/− (NSG) mice. Tumor induced mortality in mice injected with CML14736 was 68% while 100% of mice injected with PTLD 13271 succumbed to PTLD by day 70. Based on aggressiveness, PTLD 13271 was selected for further development and re-passage into NSG mice resulting in increased Tumor burden and metastasis. Transduction of the PTLD 13271 cell line with a green fluorescent protein (GFP)-expressing lentivirus facilitated Tumor tracking when re-passaged in mice. Utilizing a tolerance induction strategy, GFP+ Tumors were injected into an MHC matched miniature swine and successfully followed via flow cytometry for 48 h in circulation, although Tumor engraftment was not observed. In summary, we report the development of an aggressive GFP+B-cell lymphoma cell line which has the potential for facilitating development of a large animal Tumor Model
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myeloid leukemias and virally induced lymphomas in miniature inbred swine development of a large animal Tumor Model
Frontiers in Genetics, 2015Co-Authors: Raimon Duranstruuck, Abraham J Matar, Christene A HuangAbstract:The lack of a large animal transplantable Tumor Model has limited the study of novel therapeutic strategies for the treatment of liquid cancers. Swine as a species provide a natural option based on their similarities with humans and their already extensive use in biomedical research. Specifically, the MGH miniature swine herd retains unique genetic characteristics that facilitate the study of hematopoietic cell and solid organ transplantation. Spontaneously arising liquid cancers in these swine, specifically myeloid leukemias and B cell lymphomas, closely resemble human malignancies. The ability to establish aggressive Tumor cell lines in vitro from these naturally occurring malignancies makes a transplantable Tumor Model a close reality. Here, we discuss our experience with myeloid and lymphoid Tumors in MHC characterized miniature swine and future approaches regarding the development of a large animal transplantable Tumor Model.
Simon Leung - One of the best experts on this subject based on the ideXlab platform.
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synergistic chemosensitization and inhibition of progression to androgen independence by antisense bcl 2 oligodeoxynucleotide and paclitaxel in the lncap prostate Tumor Model
International Journal of Cancer, 2001Co-Authors: Simon Leung, Hideaki Miyake, Tobias Zellweger, Anthony W Tolcher, Martin E GleaveAbstract:Bcl-2 expression is up-regulated in prostate cancer cells after androgen ablation and associated with development of androgen independence and chemoresistance. We recently reported that antisense Bcl-2 oligodeoxynucleotides (ODNs) delay progression to androgen independence in the androgen-dependent (AD) human LNCaP prostate Tumor Model. The objectives in this study were to determine whether antisense human Bcl-2 ODN enhances chemosensitivity of paclitaxel and whether combined antisense Bcl-2 ODN and paclitaxel further delays time to androgen-independent (AI) progression in the LNCaP Tumor Model. Semi-quantitative reverse transcriptast-polymerase chain reaction revealed that treatment of LNCaP cells with antisense Bcl-2 ODN decreased Bcl-2 expression in a dose-dependent and sequence-specific manner, whereas Bcl-2 expression was not affected by paclitaxel treatment. Antisense Bcl-2 ODN treatment significantly enhanced paclitaxel chemosensitivity in vitro, reducing cell viability after treatment with 1 nM paclitaxel from 76% to 42%. Characteristic apoptotic DNA laddering was demonstrated after combined treatment with 500 nM antisense Bcl-2 ODN and 1 nM paclitaxel but not with either agent alone. Adjuvant in vivo administration of combined antisense Bcl-2 and polymeric micellar paclitaxel after castration resulted in a significant delay of emergence of AI recurrent LNCaP Tumors compared with either agent alone. By 15 weeks post castration, Tumor volume in mice treated with antisense Bcl-2 ODN alone or mismatch control ODN plus paclitaxel was >3-fold higher than in mice treated with combined antisense Bcl-2 ODN and paclitaxel. Mean serum prostate-specific antigen levels returned to or were above precastration levels by 11 weeks post castration in mice treated with antisense Bcl-2 ODN alone or mismatch control ODN plus paclitaxel but remained 90% below the pre-castration level in mice treated with combined antisense Bcl-2 ODN and paclitaxel. These findings identify combined antisense Bcl-2 and paclitaxel as a potentially new therapeutic strategy for advanced prostate cancer by enhancing paclitaxel chemosensitivity and delaying progression of hormone-refractory prostate cancer. © 2001 Wiley-Liss, Inc.
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synergistic chemosensitization and inhibition of progression to androgen independence by antisense bcl 2 oligodeoxynucleotide and paclitaxel in the lncap prostate Tumor Model
International Journal of Cancer, 2001Co-Authors: Simon Leung, Hideaki Miyake, Tobias Zellweger, Anthony W Tolcher, Martin E GleaveAbstract:Bcl-2 expression is up-regulated in prostate cancer cells after androgen ablation and associated with development of androgen independence and chemoresistance. We recently reported that antisense Bcl-2 oligodeoxynucleotides (ODNs) delay progression to androgen independence in the androgen-dependent (AD) human LNCaP prostate Tumor Model. The objectives in this study were to determine whether antisense human Bcl-2 ODN enhances chemosensitivity of paclitaxel and whether combined antisense Bcl-2 ODN and paclitaxel further delays time to androgen-independent (AI) progression in the LNCaP Tumor Model. Semi-quantitative reverse transcriptast-polymerase chain reaction revealed that treatment of LNCaP cells with antisense Bcl-2 ODN decreased Bcl-2 expression in a dose-dependent and sequence-specific manner, whereas Bcl-2 expression was not affected by paclitaxel treatment. Antisense Bcl-2 ODN treatment significantly enhanced paclitaxel chemosensitivity in vitro, reducing cell viability after treatment with 1 nM paclitaxel from 76% to 42%. Characteristic apoptotic DNA laddering was demonstrated after combined treatment with 500 nM antisense Bcl-2 ODN and 1 nM paclitaxel but not with either agent alone. Adjuvant in vivo administration of combined antisense Bcl-2 and polymeric micellar paclitaxel after castration resulted in a significant delay of emergence of AI recurrent LNCaP Tumors compared with either agent alone. By 15 weeks post castration, Tumor volume in mice treated with antisense Bcl-2 ODN alone or mismatch control ODN plus paclitaxel was >3-fold higher than in mice treated with combined antisense Bcl-2 ODN and paclitaxel. Mean serum prostate-specific antigen levels returned to or were above precastration levels by 11 weeks post castration in mice treated with antisense Bcl-2 ODN alone or mismatch control ODN plus paclitaxel but remained 90% below the pre-castration level in mice treated with combined antisense Bcl-2 ODN and paclitaxel. These findings identify combined antisense Bcl-2 and paclitaxel as a potentially new therapeutic strategy for advanced prostate cancer by enhancing paclitaxel chemosensitivity and delaying progression of hormone-refractory prostate cancer.
