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You searched for +publisher:"Temple University" +contributor:("Yang, Xiaolu;"). Showing records 1 – 2 of 2 total matches.

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Temple University

1. Virtue, Anthony Thomas. The Contributions of miR-155 in Obesity, Metabolic Syndrome, and Atherosclerosis Development.

Degree: PhD, 2014, Temple University

Pharmacology

The global incidence of overweight and obese individuals has skyrocketed in the past few decades resulting in a new health epidemic. In 1980, 5% of males and 8% of females were categorized as obese; by 2008 these values doubled equating to half a billion adults worldwide. This surge of overweight and obese individuals has driven a dramatic increase in people afflicted with metabolic disorders. As such, the term "metabolic syndrome" (MetS) has been coined to describe several interrelated metabolic risk factors which often present in concert. Specifically, metabolic syndrome refers to the presence of at least three of the following five conditions: central obesity, elevated triglycerides, diminished high density lipoprotein (HDL) cholesterol, hypertension, and insulin resistance (IR). MetS is a major health concern due to its ability to increase the likelihood of cardiovascular disease (CVD), diabetes, and other life-threatening ailments. In light of this growing medical epidemic, we have concentrated our efforts in evaluating the role of microRNA-155 (miR-155) in MetS development. MicroRNAs are a newly defined class of small, non-coding RNA which contain the unique ability to regulate gene expression through RNA interference. As a result of this ability, microRNAs can mediate a wide variety of cellular processes. In order to evaluate the function of miR-155 in MetS, we established a novel miR-155-/-/ApoE-/- (DKO) mouse model. Coupling this model with the use of normal rodent or high fat diets allowed us to investigate how states of caloric balance and surplus affected the manifestation of the individual MetS components. We found that male and female DKO mice fed a high fat diet had significantly augmented body masses of 18% and 10% respectively, when compared to ApoE-/- counterparts on the same diet. Evaluation of this phenotype with body composition analysis revealed an 18% and 46% increase in body fat percentage among the male DKO mice on normal and high fat diets, respectively. This trend was also observed in female DKO mice, albeit to a lesser extent. This phenotype was further substantiated by the observation of augmented gonadal white adipose tissue pad mass within male and female DKO mice fed either chow. This equated to a 43% and 112% increase in male mice and a 45% and 57% augmentation in female mice for normal and high fat chow diets, respectively. In light of our findings, we also evaluated how miR-155 impacted glucose and insulin sensitivity. We found levels of insulin to be augmented by 181% and 148% in male DKO mice on normal and high fat diets, respectively. Furthermore, we found these mice to be euglycemic. These observations suggest that DKO mice are IR but capable of compensating for their insensitivity with elevated insulin production. Due to the tight association between MetS and the development of non-alcoholic fatty liver disease (NAFLD) as well as CVD, we felt it prudent to investigate the manifestation of these conditions. We found elevated hepatic mass of 40% and 13%…

Advisors/Committee Members: Yang, Xiao-feng;, Wang, Hong, Ashby, Barrie, Autieri, Michael V., Muniswamy, Madesh, Yang, Xiaolu;.

Subjects/Keywords: Biology; Molecular biology;

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Virtue, A. T. (2014). The Contributions of miR-155 in Obesity, Metabolic Syndrome, and Atherosclerosis Development. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,276607

Chicago Manual of Style (16th Edition):

Virtue, Anthony Thomas. “The Contributions of miR-155 in Obesity, Metabolic Syndrome, and Atherosclerosis Development.” 2014. Doctoral Dissertation, Temple University. Accessed April 10, 2021. http://digital.library.temple.edu/u?/p245801coll10,276607.

MLA Handbook (7th Edition):

Virtue, Anthony Thomas. “The Contributions of miR-155 in Obesity, Metabolic Syndrome, and Atherosclerosis Development.” 2014. Web. 10 Apr 2021.

Vancouver:

Virtue AT. The Contributions of miR-155 in Obesity, Metabolic Syndrome, and Atherosclerosis Development. [Internet] [Doctoral dissertation]. Temple University; 2014. [cited 2021 Apr 10]. Available from: http://digital.library.temple.edu/u?/p245801coll10,276607.

Council of Science Editors:

Virtue AT. The Contributions of miR-155 in Obesity, Metabolic Syndrome, and Atherosclerosis Development. [Doctoral Dissertation]. Temple University; 2014. Available from: http://digital.library.temple.edu/u?/p245801coll10,276607


Temple University

2. Wagner, Jessica Michelle. Investigation of a novel small molecule TRAIL inducer, ONC201: pre-clinical anti-cancer efficacy, anti-metastasis effects, tumor immunity; and the structure-activity relationships (SAR) and mechanism of action of potential analogues.

Degree: PhD, 2018, Temple University

Cancer Biology & Genetics

ONC201 is a novel compound that upregulates endogenous TNF-Related Apoptosis-Inducing Ligand (TRAIL), in tumor and normal cells, restoring autocrine and paracrine anti-tumor activity within tumor cells, and upregulates the DR5 gene by activating the integrated stress response, inducing eIF2-alpha-dependent ATF4 and CHOP [1-3]. ONC201 also demonstrates potent anti-tumor effects on colorectal cancers [4, 5]. ONC201 presented a promising oral bioavailability, wide distribution throughout the body, and ability to cross the blood-brain barrier. Further, the unique ability of its TRAIL-and-DR5-based signaling to induce apoptosis in cancer cells and not normal cells adds to its appeal as an anti-cancer therapeutic and prompted clinical development [1-4, 6]. ONC201 has successfully completed an FDA advanced Phase I/II clinical trial in advanced aggressive refractory solid tumors. Results indicated that ONC201 is well-tolerated and recommended a phase II dose of 625 mg orally every 3 weeks. Several Phase I/II clinical trials are enrolling in multiple solid tumors and hematological malignancies [7, 8]. Chapter two of this study provides evidence that ONC201 dose intensification demonstrates an increased pharmacodynamic effect and an increasing anti-tumor efficacy in vivo while having a safe toxicity profile upon weekly dosing. This data influenced the Phase II clinical trials, which have now been adjusted to include weekly dosing. Given the potential anti-metastatic effects of TRAIL signaling and the role of TRAIL in the immune surveillance of cancer, we hypothesized that ONC201 would suppress metastatic tumor development and engage the immune system in its anti-cancer activity. We also establish that ONC201 provides an important anti-metastatic effect in CRC that should be pursued in both pre-clinical and clinical studies. Tail vein and surgical CRC models demonstrate that ONC201 inhibits the number and size of metastases. Evidence has shown that TRAIL can also inhibit cancer metastasis by possibly inducing cell death or TRAIL-sensitization in the primary tumor when cells undergo extravasation upon detachment from the primary tumor [9-11]. While we show that TRAIL plays a role in ONC201’s ability to inhibit migration/invasion in vitro, further investigation of the role of TRAIL in vivo is necessary. Our data indicates that ONC201 promotes a pro-immune response in CRC subcutaneous tumors with increased NK cells that play a role in ONC201’s efficacy in syngeneic models. Since activated natural killer cells express TRAIL, we established that ON201 can activate and induce TRAIL expression in NK cells [12, 13]. As we did not find any immune infiltrates in the metastases, we suggest that the effect of the micro-environment or in more clinically-relevant models with stromal environments should be pursued. Chapter 3 of this of thesis demonstrates the characterization of ONC201’s core structure and development of ONC201 analogues including their mechanistic differences and potential in vivo efficacy and…

Advisors/Committee Members: El-Deiry, Wafik S.;, Grana-Amat, Xavier, Golemis, Erica, Haines, Dale, Yang, Xiaolu;.

Subjects/Keywords: Biology; Pharmacology;

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Wagner, J. M. (2018). Investigation of a novel small molecule TRAIL inducer, ONC201: pre-clinical anti-cancer efficacy, anti-metastasis effects, tumor immunity; and the structure-activity relationships (SAR) and mechanism of action of potential analogues. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,499420

Chicago Manual of Style (16th Edition):

Wagner, Jessica Michelle. “Investigation of a novel small molecule TRAIL inducer, ONC201: pre-clinical anti-cancer efficacy, anti-metastasis effects, tumor immunity; and the structure-activity relationships (SAR) and mechanism of action of potential analogues.” 2018. Doctoral Dissertation, Temple University. Accessed April 10, 2021. http://digital.library.temple.edu/u?/p245801coll10,499420.

MLA Handbook (7th Edition):

Wagner, Jessica Michelle. “Investigation of a novel small molecule TRAIL inducer, ONC201: pre-clinical anti-cancer efficacy, anti-metastasis effects, tumor immunity; and the structure-activity relationships (SAR) and mechanism of action of potential analogues.” 2018. Web. 10 Apr 2021.

Vancouver:

Wagner JM. Investigation of a novel small molecule TRAIL inducer, ONC201: pre-clinical anti-cancer efficacy, anti-metastasis effects, tumor immunity; and the structure-activity relationships (SAR) and mechanism of action of potential analogues. [Internet] [Doctoral dissertation]. Temple University; 2018. [cited 2021 Apr 10]. Available from: http://digital.library.temple.edu/u?/p245801coll10,499420.

Council of Science Editors:

Wagner JM. Investigation of a novel small molecule TRAIL inducer, ONC201: pre-clinical anti-cancer efficacy, anti-metastasis effects, tumor immunity; and the structure-activity relationships (SAR) and mechanism of action of potential analogues. [Doctoral Dissertation]. Temple University; 2018. Available from: http://digital.library.temple.edu/u?/p245801coll10,499420

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