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035 a| (Sirsi) o936213494;

035 a| (OCoLC)936213494;

049 a| EREE;

100 1 a| Wang, Leie| author.=| ^A722244;

245 10 a| Retinoids potentiate clinically relevant cellular responses through RAR[alpha] /RXR nuclear receptor synergism in cutaneous T Cell Lymphoma /c| by Lei Wang.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2015.;

300 a| 173 pages :b| illustrations (some color).;

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| PDFc| 4.10 MB2| rda;

490 1 a| ECU Brody School of Medicine thesis;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| Ph.D.c| East Carolina Universityd| 2015.;

500 a| Presented to the Academic Faculty of the Department of Biochemistry & Molecular Biology.;

500 a| Advisor: Lance C. Bridges.;

500 a| Title from PDF t.p. (viewed March 2, 2016).;

504 a| Includes bibliographical references.;

520 3 a| The heterogeneity of cutaneous T cell lymphoma (CTCL) has stifled treatment options and hindered cure development. Despite the heterogeneous nature of CTCLs, a hallmark of all variants is malignant T cell infiltration of and/or proliferation within the skin. Therapeutic mechanisms aimed at resolving the shared attribute of dysregulated T cell trafficking embody an inclusive treatment with the broadest impact. Retinoids, natural and synthetic vitamin A derivatives, govern immune cell homing by inducing gut-specific receptors that naturally target cells away from the skin. Even though retinoids have been used to treat CTCL for over three decades, how the natural role of retinoids relates to therapeutic effectiveness is not known. In addition, the full clinical potential of retinoids is unrealized due to associated deleterious metabolic side effects, including hypertriglyceridemia, hypercholesterolemia, and hypothyroidism. Although the fundamentals of how retinoids activate ligand-dependent nuclear receptors to elicit immune cell responses are understood, the particular receptors that drive clinically beneficial outcomes (e.g. apoptosis) in malignant CTCLs are not known. This dissertation demonstrates that retinoids induce gut-specific trafficking receptors in CTCL variants, prior to the induction of apoptosis and growth inhibition. The current work delineates that heightened retinoid responsiveness is achieved through RAR[alpha]/RXR synergism. Strikingly, as compared to current regiments, this novel approach accelerates CTCL apoptosis to occur in half the time with a 2,000 fold lower dose of retinoids. The current study provides a novel mechanism of retinoid action in predisposing CTCL cells to growth arrest and apoptosis by governing cell homing properties, and establishes that receptor isotype specific agonism and synergism could increase efficacy and circumvent the deleterious off-target effects commonly associated with retinoid therapies.;

650 2 a| Lymphoma, T-Cell, Cutaneous.=| ^A1204552;

650 2 a| Retinoids.=| ^A1023179;

650 2 a| Receptors, Cytoplasmic and Nuclear.=| ^A934297;

650 2 a| Receptors, Retinoic Acid.=| ^A959293;

653 a| Vitamin A;

653 a| Adhesion;

700 1 a| Bridges, Lance,e| degree supervisor.?| UNAUTHORIZED;

710 2 a| East Carolina University.b| Department of Biochemistry and Molecular Biology.?| UNAUTHORIZED;

830 0 a| ECU Brody School of Medicine thesis.=| ^A964744;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/5124;

949 o| wjh;

994 a| C0b| ERE;

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596 a| 1 4;

998 a| 4356311;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4356311-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 1/29/2016x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4356311-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 1/29/2016x| ETDz| HERESOURCE;

Retinoids potentiate clinically relevant cellular responses through RAR[alpha] /RXR nuclear receptor synergism in cutaneous T Cell Lymphoma / by Lei Wang.

Author/creator	Wang, Lei author.
Other author	Bridges, Lance, degree supervisor.
Other author	East Carolina University. Department of Biochemistry and Molecular Biology.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2015.
Description	173 pages : illustrations (some color).
Supplemental Content	Access via ScholarShip
Subjects	Lymphoma, T-Cell, Cutaneous. Retinoids. Receptors, Cytoplasmic and Nuclear. Receptors, Retinoic Acid.

Series	ECU Brody School of Medicine thesis ECU Brody School of Medicine thesis. ^A964744
Summary	The heterogeneity of cutaneous T cell lymphoma (CTCL) has stifled treatment options and hindered cure development. Despite the heterogeneous nature of CTCLs, a hallmark of all variants is malignant T cell infiltration of and/or proliferation within the skin. Therapeutic mechanisms aimed at resolving the shared attribute of dysregulated T cell trafficking embody an inclusive treatment with the broadest impact. Retinoids, natural and synthetic vitamin A derivatives, govern immune cell homing by inducing gut-specific receptors that naturally target cells away from the skin. Even though retinoids have been used to treat CTCL for over three decades, how the natural role of retinoids relates to therapeutic effectiveness is not known. In addition, the full clinical potential of retinoids is unrealized due to associated deleterious metabolic side effects, including hypertriglyceridemia, hypercholesterolemia, and hypothyroidism. Although the fundamentals of how retinoids activate ligand-dependent nuclear receptors to elicit immune cell responses are understood, the particular receptors that drive clinically beneficial outcomes (e.g. apoptosis) in malignant CTCLs are not known. This dissertation demonstrates that retinoids induce gut-specific trafficking receptors in CTCL variants, prior to the induction of apoptosis and growth inhibition. The current work delineates that heightened retinoid responsiveness is achieved through RAR[alpha]/RXR synergism. Strikingly, as compared to current regiments, this novel approach accelerates CTCL apoptosis to occur in half the time with a 2,000 fold lower dose of retinoids. The current study provides a novel mechanism of retinoid action in predisposing CTCL cells to growth arrest and apoptosis by governing cell homing properties, and establishes that receptor isotype specific agonism and synergism could increase efficacy and circumvent the deleterious off-target effects commonly associated with retinoid therapies.
General note	Presented to the Academic Faculty of the Department of Biochemistry & Molecular Biology.
General note	Advisor: Lance C. Bridges.
General note	Title from PDF t.p. (viewed March 2, 2016).
Dissertation note	Ph.D. East Carolina University 2015.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

Retinoids potentiate clinically relevant cellular responses through RAR[alpha] /RXR nuclear receptor synergism in cutaneous T Cell Lymphoma / by Lei Wang.

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