Medicine and Health Sciences Commons^™

Characterizing The Role Of The Neuropeptide Y-Y5r System In Breast Cancer, Jenna Kara

Electronic Thesis and Dissertation Repository

Studies have demonstrated a correlation between stress and an increased risk of breast cancer. Neuropeptide Y (NPY) is up- regulated in chronic stress and induces proliferation and chemotaxis of 4T1 breast cancer cells via Y5 receptor (Y5R) activation. In the studies performed in this thesis, we characterize NPY-Y5R as a regulatory system that promotes breast cancer metastasis. We compared three cancer cell sublines derived from the same murine mammary fat pad tumour, that greatly differ in metastatic potential (67NR, 168FARN, and 4T1) in addition to a 4T1-Y5R knockdown established in our labs. In this thesis we demonstrate significance of up-regulation …

Magnetic Resonance Imaging Of Breast Cancer Brain Metastasis Progression And Responses To Radiotherapy, Donna H. Murrell

Electronic Thesis and Dissertation Repository

Introduction: The incidence of brain metastasis due to breast cancer is increasing and prognosis is poor. Treatment is challenging for this disease because systemic therapy has limited efficacy due to the presence of the blood-brain barrier. In addition, it is thought that disseminated dormant cancer cells persist in metastatic organs and may evade treatment, thereby facilitating a mechanism for later recurrence. Methods: In this thesis, we use contrast-enhanced MRI and high resolution anatomical MRI to characterize blood-brain barrier integrity associated with the development of brain metastases due to HER2+ breast cancer in the SUM-190-BR3, JIMT-1-BR3, and MDA-MB-231-BR-HER2 experimental models. We …

Development Of Rational Combination Therapy With Parp Inhibitors And Kinase Inhibitors In Tnbc, Wen-Hsuan Yu

Dissertations & Theses (Open Access)

Poly (ADP-ribose) polymerase inhibitors (PARPi) emerge as potential targeting drugs for BRCA-deficient cancers including triple negative breast cancer (TNBC). However, it has been reported that a subgroup of patients even with BRCA mutation fails to respond to PARPi in multiple clinical trials. In this study, we identified c-Met, a tyrosine kinase, phosphorylates PARP1 at Y907 and that the phosphorylation increases PARP1 activity, thereby rendering cancer cells resistant to PARPi. The combination of c-Met inhibitors (METi) and PARPi has a synergistic effect for c-Met overexpressed TNBC in vitro and in vivo. In addition to c-Met, through functional analysis, we found …

Does The Expression Of Ki-67, P16 And Cox-2 At Initial Diagnosis Of Breast Atypia Or Usual Ductal Hyperplasia Predict A Second Clinically Significant Event?, Judy A. Tjoe, Philippe Gascard, Jianxin Zhao, Gary F. Neitzel, Maharaj Singh, Brittany Last, James Marx, Thea Tlsty, Sanjay Kansra

Maharaj Singh

Background: Women diagnosed with atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH) have a fivefold increased risk of developing breast cancer. Because ADH/ALH can be precursors or predictive markers of a subsequent clinically significant event (SCSE), i.e. atypia, in situ or invasive carcinoma, the clinical outcome for these patients ranges anywhere from remission to invasive malignancy. Currently we cannot predict which atypical breast lesion is likely to be associated with future cancer, resulting in aggressive management and, possibly, overtreatment. Kerlikowske et al. reported that a combination of three biomarkers (cell cycle regulator p16INK4a, proliferation antigen Ki-67 and stress response …

Characterization Of Microbial Communities In The Mammary Glands And The Influence Of This Microbiota On Health And Disease, Camilla Urbaniak

Electronic Thesis and Dissertation Repository

The collective microbes and their genomic activity within us, referred to as the human microbiome, is crucial in maintaining health, and disruptions in composition and activity have been associated with various diseases. Considering the importance of breast milk in neonatal development and the high rate of breast cancer in women, the objective of my thesis was to obtain a comprehensive analysis of the microbiota of the mammary glands and to examine the influence of these organisms on health and disease.

Human milk is an important source of bacteria for the developing infant. While a variety of studies over the last …

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 …

Does The Expression Of Ki-67, P16 And Cox-2 At Initial Diagnosis Of Breast Atypia Or Usual Ductal Hyperplasia Predict A Second Clinically Significant Event?, Judy Tjoe, Philippe Gascard, Jianxin Zhao, Gary Neitzel, Maharaj Singh, Brittany Last, James Marx, Thea Tlsty, Sanjay Kansra

Judy Tjoe, MD

Background: Women diagnosed with atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH) have a fivefold increased risk of developing breast cancer. Because ADH/ALH can be precursors or predictive markers of a subsequent clinically significant event (SCSE), i.e. atypia, in situ or invasive carcinoma, the clinical outcome for these patients ranges anywhere from remission to invasive malignancy. Currently we cannot predict which atypical breast lesion is likely to be associated with future cancer, resulting in aggressive management and, possibly, overtreatment. Kerlikowske et al. reported that a combination of three biomarkers (cell cycle regulator p16INK4a, proliferation antigen Ki-67 and stress response …

The Role Of Fdg Pet/Ct In Detection Of Distant Metastasis In Theinitial Staging Of Breast Cancer, Anar Aliyev, Sabi̇re Yilmaz Aksoy, Meftune Özhan, Özgül Ekmekçi̇oğlu, Betül Vatankulu, Pinar Çi̇ğdem Kocael, Muhammet Sai̇t Sağer, Meli̇h Engi̇n Erkan, Keri̇m Sönmezoğlu, Meti̇n Halaç

Turkish Journal of Medical Sciences

Background/aim: We aimed to evaluate the role of FDG PET/CT in the detection of extraaxillary regional nodal/distant metastasis in breast cancer patients and to assess the value of FDG PET/CT for detecting distant metastases in patient subgroups. Materials and methods: A total of 254 patients with breast cancer (248 female, 6 male) who underwent PET/CT for initial staging were enrolled. Patients were divided into four groups: Group 1 consisted of 154 patients diagnosed by tru-cut/core/FNAB, Group 2 comprised 32 patients diagnosed by excisional biopsy, Group 3 included 62 patients who had mastectomy-axillary lymph node dissection, and Group 4 consisted of …

Efficacy Of Pegylated Liposomal Etoposide Nanoparticles On Breast Cancer Cell Lines, Mohammadreza Mehrabi, Parisa Esmaeilpour, Azim Akbarzadeh, Zahra Saffari, Maryam Farahnak, Ali Farhangi, Mohsen Chiani

Turkish Journal of Medical Sciences

Background/aim: This study aimed to investigate the efficacy of pegylated liposomal etoposide nanoparticles (NPs) against T-47D and MCF-7 breast cancer cell lines. Materials and methods: Pegylated liposomal etoposide NPs were prepared by reverse phase evaporation method. The size, size distribution, and zeta potential of the NPs was measured by a Zetasizer instrument. The cytotoxicity of NPs was inspected by methyl thiazol tetrazolium assay. The release pattern of the drug from the vesicles was studied by the dialysis method. Drug loading and encapsulation efficiency (EE) were also measured. Results: The mean size, size distribution, and zeta potential of pegylated liposomal etoposide …

Combination Immunotherapy With Extract Of Heated 4t1 And Naloxone In Mouse Model Of Breast Cancer, Shervin Jahangiri, Seyyed Meysam Abtahi Froushani, Norouz Delirezh

Turkish Journal of Medical Sciences

Background/aim: This study was designed to investigate the efficacy of a new vaccine against breast cancer, which was made by mixing the extract of heated 4T1 cells and naloxone, as an adjuvant. Materials and methods: Female BALB/c mice of 6-8 weeks old were challenged subcutaneously in the right flanks with 4T1 cells. When all animals developed a palpable tumor, immunotherapy was initiated. Mice in the experimental groups received, twice with a 1-week interval, either the extract of heated 4T1 alone or in combination with naloxone, and mice in the negative control group received phosphate-buffered saline. One week after the last …

Quantitative Comparison Of Immunohistochemical And Pcr Analysis Of Midkine Expression In Breast Cancer Types And Serum Midkine Level, Hülya Çeti̇n Sorkun, Meti̇n Akbulut, Yaşar Enli̇, Emre Tepeli̇, Sevgi̇ Özkan, Ergün Erdem

Turkish Journal of Medical Sciences

Background/aim: Midkine (MK), a heparin-binding growth factor, has an important role in cancer progression. The aim of this study was to determine MK expression in breast tissue and the preoperative and postoperative serum levels of patients with breast cancer. Materials and methods: Sixty-one patients with breast cancer participated in our study. The MK serum levels were measured pre- and postoperatively for these patients. We also analyzed breast tissues of the 61 patients immunohistochemically. We examined serum midkine levels in 49 healthy volunteers. Results: MK expression was observed in 44 (72.1%) of 61 breast cancer patients. In breast cancer patients the …

Examination Of Factors Affecting Women?S Barrier Perception To Participate In Breast Cancer Screenings In A Region Affiliated With A Family Health Center In Turkey, Fatma Ersi̇n, Peri̇han Polat

Turkish Journal of Medical Sciences

Background/aim: This study was conducted in order to determine the factors related to women's barrier perception to participate in breast cancer screenings in a region affiliated with a family health center. Materials and methods: The study was a cross-sectional study. The sample group of the study consisted of 300 women. Descriptive statistics, t test, and Mann-Whitney U test were performed for the analysis of the data. Results: Breast self-examination (BSE) and mammography barrier perception mean score of those who were illiterate in terms of educational status, and BSE and mammography barrier perception mean score of those who were single in …

Regulation Of Breast Cancer Metastasis By Sin3 Chromatin Remodeling Complexes, Monica Jeanene Lewis

All ETDs from UAB

Metastasis continues to be the most difficult clinical challenge for breast cancer. Survival rates for patients with metastatic breast cancer have not significantly changed in the past 20 years. Therefore, we need a better understanding of the molecular mechanisms that regulate breast cancer metastasis to develop effective therapies. SIN3 chromatin remodeling complexes have been implicated in breast cancer progression. Mammalian cells have two paralogs of SIN3 (SIN3A and SIN3B) that are encoded by distinct genes and have unique functions during development. However, specific roles for SIN3A and SIN3B in breast cancer progression have not been characterized. To better understand how …

Interplay Between Her2, Parp1, And Nf-Κb In Breast Cancer: Potential Therapeutic Implications, Monicka Ewa Wielgos

All ETDs from UAB

We previously reported that HER2+ breast cancers are susceptible to Poly (ADP-Ribose) polymerase inhibitors (PARPi) alone, agents that are efficacious against homologous recombination (HR) deficient tumors. However, this phenomenon was determined to be independent of a HR repair deficiency but rather due to suppression of NF-κB activity and signaling by PARP inhibition. Further, HER2 overexpression itself was necessary and sufficient to confer this susceptibility. Interestingly, PARP1 and phosphorylated RelA/p65 (NF-κB) levels were found to be elevated in human HER2+ breast cancers compared to luminal breast cancers. These data suggest a possible interplay between HER2, PARP1, and NF-κB, and how this …