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001 on1021186448;

003 OCoLC;

005 20180511101000.0;

006 m o d ;

007 cr unu||||||||;

008 180201s2017 ncua obm 000 0 eng d;

035 a| (Sirsi) o1021186448;

035 a| (OCoLC)1021186448;

049 a| EREE;

100 1 a| Ladin, Daniel A.,e| author.?| UNAUTHORIZED;

245 10 a| Synthesis and molecular evaluation of 15-deoxy-[delta]¹²,¹⁴-prostamide J₂ as a novel anti-skin cancer agent /c| by Daniel A. Ladin.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2017.;

300 a| 147 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| 2.425 MB2| rda;

490 1 a| ECU Brody School of Medicine dissertation;

538 a| System requirements: Adobe Reader.;

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

502 b| Ph.D.c| East Carolina Universityd| 2017.;

500 a| Presented to the faculty of the Department of Pharmacology and Toxicology;

500 a| Advisor: Rukiyah Van Dross-Anderson;

500 a| Title from PDF t.p. (viewed March 20, 2018).;

520 3 a| Skin cancers including non-melanoma skin cancer (NMSC) and melanoma are the most common form of cancer in the United States and thus represent a substantial burden to the health care system. Current chemotherapeutic treatments for skin cancer cause harmful side effects due to lack of tumor-cell selectivity. Our group previously found that the endocannabinoid, arachidonoyl-ethanolamide (AEA), induces apoptosis in tumor but not non-tumor cell lines through its metabolism to novel J-series prostaglandin-ethanolamides (prostamides). Therefore, the goal of this study was to synthesize the novel prostamide, 15-deoxy-[delta]¹²,¹⁴-prostamide J₂ (15d-PMJ₂) and determine the molecular mechanism of its antineoplastic activity. To our knowledge, we are the first group to successfully synthesize and biologically characterize a J-series prostamide. 15d-PMJ₂ exhibited potent and selective apoptotic properties in both non-melanoma and melanoma skin cancers. Furthermore, 15d-PMJ₂ was a potent inducer of tumor cell apoptosis in vivo. Induction of endoplasmic reticulum (ER) stress was required for 15d-PMJ₂ -mediated cancer cell death and was an important determinant of selective toxicity. This project also conducted a targeted structure-activity assessment of the electrophilic double bond, definitively showing this moiety as the molecular "warhead" necessary for the cytotoxic activity. Taken together, these data provide sound evidence that 15d-PMJ₂ may provide a clinical alternative for treatment of non-melanoma and melanoma skin cancer with less adverse effects.;

504 a| Includes bibliographical references.;

650 2 a| Antineoplastic Agents0| (DNLM)D000970=| ^A918039;

650 2 a| Skin Neoplasms0| (DNLM)D012878=| ^A918527;

650 2 a| Dermatologic Agents0| (DNLM)D003879=| ^A921692;

653 a| prostamide;

653 a| cancer chemotherapy;

653 a| prostaglandin ethanolamide;

653 a| antineoplastic;

653 a| anti-cancer therapeutic;

653 a| melanoma;

653 a| non-melanoma skin cancer;

653 a| cell death;

653 a| apoptosis;

653 a| endoplasmic reticulum stress;

700 1 a| Van Dross-Anderson, Rukiyah,e| degree supervisor.?| UNAUTHORIZED;

710 2 a| East Carolina University.b| Department of Pharmacology and Toxicology.?| UNAUTHORIZED;

830 0 a| ECU Brody School of Medicine dissertation.?| UNAUTHORIZED;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/6490;

994 a| C0b| ERE;

096 a| QV 269;

596 a| 1 4;

998 a| 4814942;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4814942-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 2/1/2018x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4814942-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 2/1/2018x| ETDz| HERESOURCE;

Synthesis and molecular evaluation of 15-deoxy-[delta]¹²,¹⁴-prostamide J₂ as a novel anti-skin cancer agent / by Daniel A. Ladin.

Author/creator	Ladin, Daniel A. author.
Other author	Van Dross-Anderson, Rukiyah, degree supervisor.
Other author	East Carolina University. Department of Pharmacology and Toxicology.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2017.
Description	147 pages : illustrations (some color).
Supplemental Content	Access via ScholarShip
Subjects	Antineoplastic Agents Skin Neoplasms Dermatologic Agents

Series	ECU Brody School of Medicine dissertation ECU Brody School of Medicine dissertation. UNAUTHORIZED
Summary	Skin cancers including non-melanoma skin cancer (NMSC) and melanoma are the most common form of cancer in the United States and thus represent a substantial burden to the health care system. Current chemotherapeutic treatments for skin cancer cause harmful side effects due to lack of tumor-cell selectivity. Our group previously found that the endocannabinoid, arachidonoyl-ethanolamide (AEA), induces apoptosis in tumor but not non-tumor cell lines through its metabolism to novel J-series prostaglandin-ethanolamides (prostamides). Therefore, the goal of this study was to synthesize the novel prostamide, 15-deoxy-[delta]¹²,¹⁴-prostamide J₂ (15d-PMJ₂) and determine the molecular mechanism of its antineoplastic activity. To our knowledge, we are the first group to successfully synthesize and biologically characterize a J-series prostamide. 15d-PMJ₂ exhibited potent and selective apoptotic properties in both non-melanoma and melanoma skin cancers. Furthermore, 15d-PMJ₂ was a potent inducer of tumor cell apoptosis in vivo. Induction of endoplasmic reticulum (ER) stress was required for 15d-PMJ₂ -mediated cancer cell death and was an important determinant of selective toxicity. This project also conducted a targeted structure-activity assessment of the electrophilic double bond, definitively showing this moiety as the molecular "warhead" necessary for the cytotoxic activity. Taken together, these data provide sound evidence that 15d-PMJ₂ may provide a clinical alternative for treatment of non-melanoma and melanoma skin cancer with less adverse effects.
General note	Presented to the faculty of the Department of Pharmacology and Toxicology
General note	Advisor: Rukiyah Van Dross-Anderson
General note	Title from PDF t.p. (viewed March 20, 2018).
Dissertation note	Ph.D. East Carolina University 2017.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

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Synthesis and molecular evaluation of 15-deoxy-[delta]¹²,¹⁴-prostamide J₂ as a novel anti-skin cancer agent / by Daniel A. Ladin.

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