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Article ; Online: Airway stem cell reconstitution by the transplantation of primary or pluripotent stem cell-derived basal cells.

Ma, Liang / Thapa, Bibek R / Le Suer, Jake A / Tilston-Lünel, Andrew / Herriges, Michael J / Berical, Andrew / Beermann, Mary Lou / Wang, Feiya / Bawa, Pushpinder S / Kohn, Anat / Ysasi, Alexandra B / Kiyokawa, Hirofumi / Matte, Taylor M / Randell, Scott H / Varelas, Xaralabos / Hawkins, Finn J / Kotton, Darrell N

Cell stem cell

2023 Volume 30, Issue 9, Page(s) 1199–1216.e7

Abstract: Life-long reconstitution of a tissue's resident stem cell compartment with engrafted cells has the potential to durably replenish organ function. Here, we demonstrate the engraftment of the airway epithelial stem cell compartment via intra-airway ... ...

Abstract	Life-long reconstitution of a tissue's resident stem cell compartment with engrafted cells has the potential to durably replenish organ function. Here, we demonstrate the engraftment of the airway epithelial stem cell compartment via intra-airway transplantation of mouse or human primary and pluripotent stem cell (PSC)-derived airway basal cells (BCs). Murine primary or PSC-derived BCs transplanted into polidocanol-injured syngeneic recipients give rise for at least two years to progeny that stably display the morphologic, molecular, and functional phenotypes of airway epithelia. The engrafted basal-like cells retain extensive self-renewal potential, evident by the capacity to reconstitute the tracheal epithelium through seven generations of secondary transplantation. Using the same approach, human primary or PSC-derived BCs transplanted into NOD scid gamma (NSG) recipient mice similarly display multilineage airway epithelial differentiation in vivo. Our results may provide a step toward potential future syngeneic cell-based therapy for patients with diseases resulting from airway epithelial cell damage or dysfunction.
MeSH term(s)	Humans ; Animals ; Mice ; Pluripotent Stem Cells ; Cell- and Tissue-Based Therapy ; Epithelial Cells ; Epithelium ; Mice, Inbred NOD ; Mice, SCID
Language	English
Publishing date	2023-08-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2375354-7
ISSN	1875-9777 ; 1934-5909
ISSN (online)	1875-9777
ISSN	1934-5909
DOI	10.1016/j.stem.2023.07.014
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Zs.A 6589: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 75: Show issues

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Article ; Online: HES factors regulate specific aspects of chondrogenesis and chondrocyte hypertrophy during cartilage development.

Rutkowski, Timothy P / Kohn, Anat / Sharma, Deepika / Ren, Yinshi / Mirando, Anthony J / Hilton, Matthew J

Journal of cell science

2016 Volume 129, Issue 11, Page(s) 2145–2155

Abstract: RBPjκ-dependent Notch signaling regulates multiple processes during cartilage development, including chondrogenesis, chondrocyte hypertrophy and cartilage matrix catabolism. Select members of the HES- and HEY-families of transcription factors are ... ...

Abstract	RBPjκ-dependent Notch signaling regulates multiple processes during cartilage development, including chondrogenesis, chondrocyte hypertrophy and cartilage matrix catabolism. Select members of the HES- and HEY-families of transcription factors are recognized Notch signaling targets that mediate specific aspects of Notch function during development. However, whether particular HES and HEY factors play any role(s) in the processes during cartilage development is unknown. Here, for the first time, we have developed unique in vivo genetic models and in vitro approaches demonstrating that the RBPjκ-dependent Notch targets HES1 and HES5 suppress chondrogenesis and promote the onset of chondrocyte hypertrophy. HES1 and HES5 might have some overlapping function in these processes, although only HES5 directly regulates Sox9 transcription to coordinate cartilage development. HEY1 and HEYL play no discernable role in regulating chondrogenesis or chondrocyte hypertrophy, whereas none of the HES or HEY factors appear to mediate Notch regulation of cartilage matrix catabolism. This work identifies important candidates that might function as downstream mediators of Notch signaling both during normal skeletal development and in Notch-related skeletal disorders.
MeSH term(s)	Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Bone Development/genetics ; Cartilage/embryology ; Cartilage/metabolism ; Cell Differentiation ; Cell Proliferation ; Chondrocytes/metabolism ; Chondrocytes/pathology ; Chondrogenesis/genetics ; Gene Expression Regulation, Developmental ; Hypertrophy ; Mesenchymal Stromal Cells/metabolism ; Mice ; Repressor Proteins/metabolism ; SOX9 Transcription Factor/metabolism ; Transcription Factor HES-1/genetics ; Transcription Factor HES-1/metabolism ; Transcription, Genetic
Chemical Substances	Basic Helix-Loop-Helix Transcription Factors ; Hes1 protein, mouse ; Hes5 protein, mouse ; Repressor Proteins ; SOX9 Transcription Factor ; Transcription Factor HES-1
Language	English
Publishing date	2016--01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.181271
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Zs.A 1200: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9.

Kohn, Anat / Rutkowski, Timothy P / Liu, Zhaoyang / Mirando, Anthony J / Zuscik, Michael J / O'Keefe, Regis J / Hilton, Matthew J

Bone research

2015 Volume 3, Page(s) 15021

Abstract: RBPjk-dependent Notch signaling regulates both the onset of chondrocyte hypertrophy and the progression to terminal chondrocyte maturation during endochondral ossification. It has been suggested that Notch signaling can regulate Sox9 transcription, ... ...

Abstract	RBPjk-dependent Notch signaling regulates both the onset of chondrocyte hypertrophy and the progression to terminal chondrocyte maturation during endochondral ossification. It has been suggested that Notch signaling can regulate Sox9 transcription, although how this occurs at the molecular level in chondrocytes and whether this transcriptional regulation mediates Notch control of chondrocyte hypertrophy and cartilage development is unknown or controversial. Here we have provided conclusive genetic evidence linking RBPjk-dependent Notch signaling to the regulation of Sox9 expression and chondrocyte hypertrophy by examining tissue-specific Rbpjk mutant (Prx1Cre;Rbpjk(f/f) ), Rbpjk mutant/Sox9 haploinsufficient (Prx1Cre;Rbpjk(f/f);Sox9(f/+) ), and control embryos for alterations in SOX9 expression and chondrocyte hypertrophy during cartilage development. These studies demonstrate that Notch signaling regulates the onset of chondrocyte maturation in a SOX9-dependent manner, while Notch-mediated regulation of terminal chondrocyte maturation likely functions independently of SOX9. Furthermore, our in vitro molecular analyses of the Sox9 promoter and Notch-mediated regulation of Sox9 gene expression in chondrogenic cells identified the ability of Notch to induce Sox9 expression directly in the acute setting, but suppresses Sox9 transcription with prolonged Notch signaling that requires protein synthesis of secondary effectors.
Language	English
Publishing date	2015-08-11
Publishing country	China
Document type	Journal Article
ZDB-ID	2803313-9
ISSN	2095-6231 ; 2095-4700
ISSN (online)	2095-6231
ISSN	2095-4700
DOI	10.1038/boneres.2015.21
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Article ; Online: Cartilage-specific RBPjκ-dependent and -independent Notch signals regulate cartilage and bone development.

Kohn, Anat / Dong, Yufeng / Mirando, Anthony J / Jesse, Alana M / Honjo, Tasuku / Zuscik, Michael J / O'Keefe, Regis J / Hilton, Matthew J

Development (Cambridge, England)

2012 Volume 139, Issue 6, Page(s) 1198–1212

Abstract: The Notch signaling pathway has emerged as an important regulator of endochondral bone formation. Although recent studies have examined the role of Notch in mesenchymal and chondro-osteo progenitor cell populations, there has yet to be a true examination ...

Abstract	The Notch signaling pathway has emerged as an important regulator of endochondral bone formation. Although recent studies have examined the role of Notch in mesenchymal and chondro-osteo progenitor cell populations, there has yet to be a true examination of Notch signaling specifically within developing and committed chondrocytes, or a determination of whether cartilage and bone formation are regulated via RBPjκ-dependent or -independent Notch signaling mechanisms. To develop a complete understanding of Notch signaling during cartilage and bone development we generated and compared general Notch gain-of-function (Rosa-NICD(f/+)), RBPjκ-deficient (Rbpjκ(f/f)), and RBPjκ-deficient Notch gain-of-function (Rosa-NICD(f/+);Rbpjκ(f/f)) conditional mutant mice, where activation or deletion of floxed alleles were specifically targeted to mesenchymal progenitors (Prx1Cre) or committed chondrocytes (inducible Col2Cre(ERT2)). These data demonstrate, for the first time, that Notch regulation of chondrocyte maturation is solely mediated via the RBPjκ-dependent pathway, and that the perichodrium or osteogenic lineage probably influences chondrocyte terminal maturation and turnover of the cartilage matrix. Our study further identifies the cartilage-specific RBPjκ-independent pathway as crucial for the proper regulation of chondrocyte proliferation, survival and columnar chondrocyte organization. Unexpectedly, the RBPjκ-independent Notch pathway was also identified as an important long-range cell non-autonomous regulator of perichondral bone formation and an important cartilage-derived signal required for coordinating chondrocyte and osteoblast differentiation during endochondral bone development. Finally, cartilage-specific RBPjκ-independent Notch signaling likely regulates Ihh responsiveness during cartilage and bone development.
MeSH term(s)	Animals ; Bone and Bones/embryology ; Cartilage/embryology ; Cartilage/metabolism ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Chondrocytes/cytology ; Chondrocytes/metabolism ; Chondrogenesis ; Gene Expression Regulation, Developmental ; Immunoglobulin J Recombination Signal Sequence-Binding Protein/deficiency ; Immunoglobulin J Recombination Signal Sequence-Binding Protein/genetics ; Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism ; Mesenchymal Stem Cells ; Mice ; Mice, Transgenic ; Osteogenesis/genetics ; Receptors, Notch/genetics ; Receptors, Notch/metabolism ; Signal Transduction
Chemical Substances	Immunoglobulin J Recombination Signal Sequence-Binding Protein ; Rbpj protein, mouse ; Receptors, Notch
Language	English
Publishing date	2012-02-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.070649
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Article ; Online: RBPjkappa-dependent Notch signaling regulates mesenchymal progenitor cell proliferation and differentiation during skeletal development.

Dong, Yufeng / Jesse, Alana M / Kohn, Anat / Gunnell, Lea M / Honjo, Tasuku / Zuscik, Michael J / O'Keefe, Regis J / Hilton, Matthew J

Development (Cambridge, England)

2010 Volume 137, Issue 9, Page(s) 1461–1471

Abstract: The Notch pathway has recently been implicated in mesenchymal progenitor cell (MPC) differentiation from bone marrow-derived progenitors. However, whether Notch regulates MPC differentiation in an RBPjkappa-dependent manner, specifies a particular MPC ... ...

Abstract	The Notch pathway has recently been implicated in mesenchymal progenitor cell (MPC) differentiation from bone marrow-derived progenitors. However, whether Notch regulates MPC differentiation in an RBPjkappa-dependent manner, specifies a particular MPC cell fate, regulates MPC proliferation and differentiation during early skeletal development or controls specific Notch target genes to regulate these processes remains unclear. To determine the exact role and mode of action for the Notch pathway in MPCs during skeletal development, we analyzed tissue-specific loss-of-function (Prx1Cre; Rbpjk(f/f)), gain-of-function (Prx1Cre; Rosa-NICD(f/+)) and RBPjkappa-independent Notch gain-of-function (Prx1Cre; Rosa-NICD(f/+); Rbpjk(f/f)) mice for defects in MPC proliferation and differentiation. These data demonstrate for the first time that the RBPjkappa-dependent Notch signaling pathway is a crucial regulator of MPC proliferation and differentiation during skeletal development. Our study also implicates the Notch pathway as a general suppressor of MPC differentiation that does not bias lineage allocation. Finally, Hes1 was identified as an RBPjkappa-dependent Notch target gene important for MPC maintenance and the suppression of in vitro chondrogenesis.
MeSH term(s)	Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Basic Helix-Loop-Helix Transcription Factors/physiology ; Blotting, Western ; Bone and Bones/cytology ; Bone and Bones/embryology ; Cell Differentiation/genetics ; Cell Differentiation/physiology ; Cell Proliferation ; Cells, Cultured ; Gene Expression Regulation, Developmental ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Homeodomain Proteins/physiology ; Immunoglobulin J Recombination Signal Sequence-Binding Protein/genetics ; Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism ; Limb Buds/cytology ; Limb Buds/embryology ; Limb Buds/metabolism ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Mice ; Models, Biological ; Receptors, Notch/genetics ; Receptors, Notch/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/genetics ; Signal Transduction/physiology ; Transcription Factor HES-1
Chemical Substances	Basic Helix-Loop-Helix Transcription Factors ; Hes1 protein, mouse ; Homeodomain Proteins ; Immunoglobulin J Recombination Signal Sequence-Binding Protein ; Prrx1 protein, mouse ; Rbpj protein, mouse ; Receptors, Notch ; Transcription Factor HES-1
Language	English
Publishing date	2010-03-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.042911
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Article ; Online: TAK1 regulates cartilage and joint development via the MAPK and BMP signaling pathways.

Gunnell, Lea M / Jonason, Jennifer H / Loiselle, Alayna E / Kohn, Anat / Schwarz, Edward M / Hilton, Matthew J / O'Keefe, Regis J

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2010 Volume 25, Issue 8, Page(s) 1784–1797

Abstract: The importance of canonical transforming growth factor beta (TGF-beta) and bone morphogenetic protein (BMP) signaling during cartilage and joint development is well established, but the necessity for noncanonical (SMAD-independent) signaling during these ...

Abstract	The importance of canonical transforming growth factor beta (TGF-beta) and bone morphogenetic protein (BMP) signaling during cartilage and joint development is well established, but the necessity for noncanonical (SMAD-independent) signaling during these processes is largely unknown. TGF-beta activated kinase 1 (TAK1) is a MAP3K activated by TGF-beta, BMP, and other mitogen-activated protein kinase (MAPK) signaling components. We set out to define the potential role for noncanonical, TAK1-mediated signaling in cartilage and joint development via deletion of Tak1 in chondrocytes (Col2Cre;Tak1(f/f)) and the developing limb mesenchyme (Prx1Cre;Tak1(f/f)). Deletion of Tak1 in chondrocytes resulted in novel embryonic developmental cartilage defects including decreased chondrocyte proliferation, reduced proliferating chondrocyte survival, delayed onset of hypertrophy, reduced Mmp13 expression, and a failure to maintain interzone cells of the elbow joint, which were not observed previously in another Col2Cre;Tak1(f/f) model. Deletion of Tak1 in limb mesenchyme resulted in widespread joint fusions likely owing to the differentiation of interzone cells to the chondrocyte lineage. The Prx1Cre;Tak1(f/f) model also allowed us to identify novel columnar chondrocyte organization and terminal maturation defects owing to the interplay between chondrocytes and the surrounding mesenchyme. Furthermore, both our in vivo models and in vitro cell culture studies demonstrate that loss of Tak1 results in impaired activation of the downstream MAPK target p38, as well as diminished activation of the BMP/SMAD signaling pathway. Taken together, these data demonstrate that TAK1 is a critical regulator of both MAPK and BMP signaling and is necessary for proper cartilage and joint development.
MeSH term(s)	Animals ; Animals, Newborn ; Apoptosis ; Bone Morphogenetic Proteins/metabolism ; Cartilage/embryology ; Cartilage/enzymology ; Cartilage/pathology ; Cell Differentiation ; Cell Proliferation ; Chondrocytes/pathology ; Joints/embryology ; Joints/enzymology ; Joints/pathology ; MAP Kinase Kinase Kinases/antagonists & inhibitors ; MAP Kinase Kinase Kinases/deficiency ; MAP Kinase Kinase Kinases/metabolism ; MAP Kinase Signaling System ; Mice ; Morphogenesis ; Mutation/genetics
Chemical Substances	Bone Morphogenetic Proteins ; MAP Kinase Kinase Kinases (EC 2.7.11.25) ; MAP kinase kinase kinase 7 (EC 2.7.11.25)
Language	English
Publishing date	2010-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1002/jbmr.79
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Article ; Online: RBP-Jκ-dependent Notch signaling is required for murine articular cartilage and joint maintenance.

Mirando, Anthony J / Liu, Zhaoyang / Moore, Tyler / Lang, Alexandra / Kohn, Anat / Osinski, Alana M / O'Keefe, Regis J / Mooney, Robert A / Zuscik, Michael J / Hilton, Matthew J

Arthritis and rheumatism

2013 Volume 65, Issue 10, Page(s) 2623–2633

Abstract: Objective: Osteoarthritis (OA) is a degenerative disease resulting in severe joint cartilage destruction and disability. While the mechanisms underlying the development and progression of OA are poorly understood, gene mutations have been identified ... ...

Abstract	Objective: Osteoarthritis (OA) is a degenerative disease resulting in severe joint cartilage destruction and disability. While the mechanisms underlying the development and progression of OA are poorly understood, gene mutations have been identified within cartilage-related signaling molecules, implicating impaired cell signaling in OA and joint disease. The Notch pathway has recently been identified as a crucial regulator of growth plate cartilage development, and components are expressed in joint tissue. This study was undertaken to investigate a novel role for Notch signaling in joint cartilage development, maintenance, and the pathogenesis of joint disease in a mouse model. Methods: We performed the first mouse gene study in which the core Notch signaling component, RBP-Jκ, was tissue specifically deleted within joints. The Prx1Cre transgene removed Rbpjk loxP-flanked alleles in mesenchymal joint precursor cells, while the Col2Cre(ERT2) transgene specifically deleted Rbpjk in postnatal chondrocytes. Murine articular chondrocyte cultures were also used to examine Notch regulation of gene expression. Results: Loss of Notch signaling in mesenchymal joint precursor cells did not affect embryonic joint development in mice, but rather, resulted in an early, progressive OA-like pathology. Additionally, partial loss of Notch signaling in murine postnatal cartilage resulted in progressive joint cartilage degeneration and an age-related OA-like pathology. Inhibition of Notch signaling altered the expression of the extracellular matrix (ECM)-related factors type II collagen (COL2A1), proteoglycan 4, COL10A1, matrix metalloproteinase 13, and ADAMTS. Conclusion: Our findings indicate that the RBP-Jκ-dependent Notch pathway is a novel pathway involved in joint maintenance and articular cartilage homeostasis, a critical regulator of articular cartilage ECM-related molecules, and a potentially important therapeutic target for OA-like joint disease.
MeSH term(s)	Animals ; Cartilage, Articular/physiology ; Cells, Cultured ; Collagen Type I/genetics ; Collagen Type I/physiology ; Collagen Type II/genetics ; Collagen Type II/physiology ; Homeostasis/physiology ; Immunoglobulin J Recombination Signal Sequence-Binding Protein/genetics ; Immunoglobulin J Recombination Signal Sequence-Binding Protein/physiology ; Joints/physiology ; Mice ; Mice, Inbred Strains ; Mice, Transgenic ; Models, Animal ; Osteoarthritis/physiopathology ; Receptors, Notch/physiology ; Signal Transduction/physiology
Chemical Substances	Col2a1 protein, mouse ; Collagen Type I ; Collagen Type II ; Immunoglobulin J Recombination Signal Sequence-Binding Protein ; Receptors, Notch ; collagen type I, alpha 1 chain
Language	English
Publishing date	2013-07-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	127294-9
ISSN	1529-0131 ; 0004-3591 ; 2326-5191
ISSN (online)	1529-0131
ISSN	0004-3591 ; 2326-5191
DOI	10.1002/art.38076
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Zs.A 24: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: A polymer library approach to suicide gene therapy for cancer.

Anderson, Daniel G / Peng, Weidan / Akinc, Akin / Hossain, Naushad / Kohn, Anat / Padera, Robert / Langer, Robert / Sawicki, Janet A

Proceedings of the National Academy of Sciences of the United States of America

2004 Volume 101, Issue 45, Page(s) 16028–16033

Abstract: Optimal gene therapy for cancer must (i) deliver DNA to tumor cells with high efficiency, (ii) induce minimal toxicity, and (iii) avoid gene expression in healthy tissues. To this end, we generated a library of >500 degradable, poly(beta-amino esters) ... ...

Abstract	Optimal gene therapy for cancer must (i) deliver DNA to tumor cells with high efficiency, (ii) induce minimal toxicity, and (iii) avoid gene expression in healthy tissues. To this end, we generated a library of >500 degradable, poly(beta-amino esters) for potential use as nonviral DNA vectors. Using high-throughput methods, we screened this library in vitro for transfection efficiency and cytotoxicity. We tested the best performing polymer, C32, in mice for toxicity and DNA delivery after intratumor and i.m. injection. C32 delivered DNA intratumorally approximately 4-fold better than one of the best commercially available reagents, jetPEI (polyethyleneimine), and 26-fold better than naked DNA. Conversely, the highest transfection levels after i.m. administration were achieved with naked DNA, followed by polyethyleneimine; transfection was rarely observed with C32. Additionally, polyethyleneimine induced significant local toxicity after i.m. injection, whereas C32 demonstrated no toxicity. Finally, we used C32 to deliver a DNA construct encoding the A chain of diphtheria toxin (DT-A) to xenografts derived from LNCaP human prostate cancer cells. This construct regulates toxin expression both at the transcriptional level by the use of a chimeric-modified enhancer/promoter sequence of the human prostate-specific antigen gene and by DNA recombination mediated by Flp recombinase. C32 delivery of the A chain of diphtheria toxin DNA to LNCaP xenografts suppressed tumor growth and even caused 40% of tumors to regress in size. Because C32 transfects tumors locally at high levels, transfects healthy muscle poorly, and displays no toxicity, it may provide a vehicle for the local treatment of cancer.
MeSH term(s)	Animals ; Biocompatible Materials ; Cell Line, Tumor ; DNA, Recombinant/administration & dosage ; DNA, Recombinant/genetics ; Diphtheria Toxin/genetics ; Genetic Therapy/methods ; Genetic Vectors ; Humans ; Male ; Materials Testing ; Mice ; Mice, Nude ; Neoplasm Proteins/biosynthesis ; Neoplasm Transplantation ; Neoplasms, Experimental/metabolism ; Neoplasms, Experimental/pathology ; Neoplasms, Experimental/therapy ; Peptide Fragments/genetics ; Polymers/chemical synthesis ; Polymers/chemistry ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology ; Prostatic Neoplasms/therapy ; Transfection ; Transplantation, Heterologous
Chemical Substances	Biocompatible Materials ; DNA, Recombinant ; Diphtheria Toxin ; Neoplasm Proteins ; Peptide Fragments ; Polymers ; diphtheria toxin fragment A
Language	English
Publishing date	2004-11-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.0407218101
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