Genetic Phenomena Commons^™

Assessing Identification Of Newly Diagnosed Breast Cancer Patients For Referral To Genetic Counseling, Corinne Marie Locke

Theses and Dissertations

Since 1998, the National Comprehensive Cancer Network (NCCN) guidelines have specified clinical indications for genetic testing for breast cancer susceptibility genes, but retrospective studies have shown that, despite meeting the NCCN criteria, patients are not always advised of the option of genetic testing. Further compounding this issue, studies have shown that cancer family history intake and documented family history can be incomplete even when taken by oncology providers. At this study site and other cancer centers in the country, patients with a new diagnosis of breast cancer are referred for genetic counseling by their cancer care team if they are …

Mimicking The Effect Of Prolactin On Stat3/Stat5 Activity In Breast Cancer, Jennifer N. Barbuto, Sarah R. Walker

Honors Theses and Capstones

Signal transducers and activators of transcription (STAT) 3 and 5 are commonly constitutively activated in breast cancer. STAT5 can outcompete STAT3 and reduce cell proliferation and metastasis. STAT5 activation is stimulated by prolactin, a natural hormone that can be harmful at high levels. The aim of this study is to identify some possible previously developed drugs that mimic the effect of prolactin and STAT5 without the added risk in MDA-MB231 breast cancer cells. Using the CLUE database query app and STAT5 up- and downregulation signatures, three drugs (X, K, and M) were chosen based on their similarity in signatures to …

A Systematic Comparison Of Lipopolymers For Sirna Delivery To Multiple Breast Cancer Cell Lines: In Vitro Studies, Hamidreza Montazeri Aliabadi, Remant Bahadur Kc, Emira Bousoik, Ashley Barbarino, Bindu Thapa, Melissa Coyle, Parvin Mahdipoor, Hasan Uludağ

Pharmacy Faculty Articles and Research

Small interfering RNA (siRNA) therapy is a promising approach for treatment of a wide range of cancers, including breast cancers that display variable phenotypic features. To explore the general utility of siRNA therapy to control aberrant expression of genes in breast cancer, we conducted a detailed analysis of siRNA delivery and silencing response in vitro in 6 separate breast cancer cell models (MDA-MB-231, MDA-MB-231-KRas-CRM, MCF-7, AU565, MDA-MB-435 and MDA-MB-468 cells). Using lipopolymers for siRNA complexation and delivery, we found a large variation in siRNA delivery efficiency depending on the specific lipopolymer used for siRNA complexation and delivery. Some lipopolymers were …

Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle

Electronic Theses and Dissertations

Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences …

Activity Of Distinct Growth Factor Receptor Network Components In Breast Tumors Uncovers Two Biologically Relevant Subtypes, Moom Roosan, Shelley M. Macneil, David F. Jenkins, Gajendra Shrestha, Sydney R. Wyatt, Jasmine A. Mcquerry, Stephen R. Piccolo, Laura M. Heiser, Joe W. Gray, W. Evan Johnson, Andrea H. Bild

Pharmacy Faculty Articles and Research

Background
The growth factor receptor network (GFRN) plays a significant role in driving key oncogenic processes. However, assessment of global GFRN activity is challenging due to complex crosstalk among GFRN components, or pathways, and the inability to study complex signaling networks in patient tumors. Here, pathway-specific genomic signatures were used to interrogate GFRN activity in breast tumors and the consequent phenotypic impact of GRFN activity patterns.

Methods
Novel pathway signatures were generated in human primary mammary epithelial cells by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS (G12V), RAF1, BAD). The pathway analysis toolkit Adaptive Signature Selection …

Identification Of Potential Drug Targets In Cancer Signaling Pathways Using Stochastic Logical Models, Peican Zhu, Hamidreza Montazeri Aliabadi, Hasan Uludag, Jie Han

Pharmacy Faculty Articles and Research

The investigation of vulnerable components in a signaling pathway can contribute to development of drug therapy addressing aberrations in that pathway. Here, an original signaling pathway is derived from the published literature on breast cancer models. New stochastic logical models are then developed to analyze the vulnerability of the components in multiple signalling sub-pathways involved in this signaling cascade. The computational results are consistent with the experimental results, where the selected proteins were silenced using specific siRNAs and the viability of the cells were analyzed 72 hours after silencing. The genes elF4E and NFkB are found to have nearly no …

Cancer Incidence In First And Second Degree Relatives Of Brca1 And Brca2 Mutation Carriers, Haley Streff

Dissertations & Theses (Open Access)

Mutations in the BRCA1 or BRCA2 genes are associated with increased risks for breast, ovarian, and several other cancers. The purpose of this study was to evaluate the incidence of cancers in first and second degree relatives of BRCA mutation carriers compared to the general population. A total of 1086 pedigrees of BRCA mutation carriers were obtained from a prospectively maintained, internal review board approved study of persons referred for clinical genetic counseling at The University of Texas MD Anderson Cancer Center. We identified 9032 first and second degree relatives from 784 pedigrees which demonstrated a clear indication of parental …