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Breast cancer

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Full-Text Articles in Cancer Biology

Targeting Breast Cancer Brain Metastasis Through Novel Combination Of Fda-Approved Orally Active Blood-Brain Barrier Permeable Ret And Tgli1 Inhibitors, Joshua Cha May 2026

Targeting Breast Cancer Brain Metastasis Through Novel Combination Of Fda-Approved Orally Active Blood-Brain Barrier Permeable Ret And Tgli1 Inhibitors, Joshua Cha

Dissertations and Theses (Open Access)

Breast cancer is the most diagnosed cancer in American women, and breast cancer brain metastasis (BCBM) exhibits the worst prognoses with a life-expectancy averaging at 6 months. This short life expectancy is largely attributed to the lack of effective treatment. Many challenges remain unsolved, including the limited number of actionable targets for targeted therapy and effective blood-brain barrier (BBB) permeable drugs that are safe without promoting drug resistance. Therefore, there is an urgent call for identification of novel therapeutic targets and development of BBB-permeable drugs. One of the potential targets identified by our lab for BCBM targeted therapy is the …


Serum Protein Signatures For Breast Cancer Detection In Treatment-Naïve African American Women Using Integrated Proteomics And Pattern Analysis, Padma Tadi Uppala, Elmer Rivera, Hyun J. Kwon, Sharon S. Lum Jan 2026

Serum Protein Signatures For Breast Cancer Detection In Treatment-Naïve African American Women Using Integrated Proteomics And Pattern Analysis, Padma Tadi Uppala, Elmer Rivera, Hyun J. Kwon, Sharon S. Lum

Faculty Publications

Breast cancer is the leading cause of cancer-related mortality in African American (AA) women. In this study we evaluated the serum proteomic profile of AA women with breast cancer using an integrated proteomic framework with multivariate pattern analysis. Using 2D-DIGE, thousands of serum protein spots were detected across 33 gels; 46 spots met criteria for presence, statistical significance, and differential expression. Proteins from the spots were identified by MALDI-TOF/TOF and matched in curated databases, highlighting serum biomarkers including ceruloplasmin, alpha-2-macroglobulin, complement component C3 and C6, alpha-1-antitrypsin, alpha-1B-glycoprotein, alpha-2-HS-glycoprotein and haptoglobin-related protein. LC-MS/MS analysis revealed 163 differentiating peptides after imputing and …


Immune Suppression And Epigenetic Reprogramming In Epithelial-Mesenchymal Transition, Hanxu Lu Jan 2026

Immune Suppression And Epigenetic Reprogramming In Epithelial-Mesenchymal Transition, Hanxu Lu

Dartmouth College Ph.D Dissertations

Epithelial-mesenchymal transition (EMT) is increasingly recognized as a dynamic spectrum of cellular programthat contributes to tumor progression, metastasis, and therapeutic resistance. Rather than existing as discrete epithelial or mesenchymal phenotypes, tumor cells undergo intermediate EMT states in which epithelial and mesenchymal features are partially and variably expressed. In this thesis, I studied EMT state heterogeneity through two complementary and integrated dimensions: tumor-immune interactions and the dynamic remodeling of epigenetic programs across the EMT spectrum. Using a clonal EMT model derived from the murine triple-negative 4T1 mammary carcinoma cell line, including epithelial, intermediate, and mesenchymal states that are stably maintained in …


Potential Role Of A Ruthenium-Based Compound Ru-Im In The Treatment Of Triple Negative Breast Cancer, Rachele Rameau Sep 2025

Potential Role Of A Ruthenium-Based Compound Ru-Im In The Treatment Of Triple Negative Breast Cancer, Rachele Rameau

Dissertations, Theses, and Capstone Projects

Triple negative breast cancer (TNBC) is an aggressive and heterogeneous molecular subtype of breast cancer that has limited available treatments. The organometallic cationic ruthenium derivative Ru-IM was found to be highly water soluble, was differentially toxic for breast cancer cells and tumors, and was involved in the pI3K/AKT/mTOR pathway. However, a full understanding of genetic and epigenetic factors that can be part of regulatory mechanisms of Ru-IM is yet to be determined. Epigenetic assays including DNA methylation, histone acetylation and histone deacetylation were performed with the half inhibitory concentration (IC50) values of Ru-IM. Bisulfite sequencing of untreated and treated MDA-MB-231 …


Co-Culture 3d Model For Breast Cancer, Anh Duc Nguyen Aug 2025

Co-Culture 3d Model For Breast Cancer, Anh Duc Nguyen

Research from the Berry Summer Thesis Institute, 2025

The ability to replicate the tumor microenvironment using 3D models have allowed researchers to study the tumors in vitro closer to their in vivo counterparts without the drawbacks of those models. The 3D co-culture model is an improved version of the 3D monoculture model, capable of replicating the tumor microenvironment, letting researchers study cancer response mechanism, tumor metastases, drug resistance, simulate cell-cell interactions, etc., in breast cancer. The models can be classified into four classes based on their formation method and content, all of which have different advantages and disadvantages.


Identification Of Methylation Patterns, Associated Dna Methylating Proteins, And Methyltransferase Inhibitors On The Promoter Regions Of Dax-1, Brandon Tyler Toy May 2025

Identification Of Methylation Patterns, Associated Dna Methylating Proteins, And Methyltransferase Inhibitors On The Promoter Regions Of Dax-1, Brandon Tyler Toy

Master's Theses

The DAX-1 gene (Dosage-Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, Critical Region on the X chromosome, gene 1) encodes for an orphan nuclear hormone receptor and its mutation is implicated in multiple diseases including congenital adrenal hypoplasia, adrenal cancer, and breast cancer. Previous research has linked DAX-1 downregulation to tumor initiation in breast tissue, suggesting the gene acts as a tumor suppressor with respect to breast cancer. Additional studies completed by the Tzagarakis-Foster laboratory have shown that methylation of the DAX-1 promoter region is heavily influential in breast cancer development, with release of epigenetic repression resulting in slowing of cellular proliferation …


Novel Combination Therapies For Estrogen Receptor-Positive Breast Cancer Driven By Rational Molecular Mechanisms, Anneka Lila Johnson May 2025

Novel Combination Therapies For Estrogen Receptor-Positive Breast Cancer Driven By Rational Molecular Mechanisms, Anneka Lila Johnson

Dartmouth College Ph.D Dissertations

Breast cancer (BC) is the most common non-keratinocyte cancer diagnosed in women in the United States with approximately 300,000 new cases diagnosed each year. Despite a myriad of treatment options, BC remains the second-most deadly cancer. Estrogen receptor-positive (ER+) BC comprises 60-70% of BC diagnoses and is treated with endocrine therapies that limit ER signaling. Despite endocrine therapy options, ~1/3 of patients experience recurrence within 10-20 years of diagnosis. Novel therapeutic strategies are required to limit BC recurrence-related morbidity and mortality.

Radiotherapy is used as an adjuvant treatment for ER+ BC patients prior to the use of endocrine therapy. Radiation …


Understanding Challenges To Breast Cancer Screening For African American Women In Detroit: A Study Of Social And Healthcare Inequities, Miranda Goodson, Whitney Bowyer, Erika Lopez, Anna Lundh Apr 2025

Understanding Challenges To Breast Cancer Screening For African American Women In Detroit: A Study Of Social And Healthcare Inequities, Miranda Goodson, Whitney Bowyer, Erika Lopez, Anna Lundh

Medical Student Research Symposium

African American (AA) women have lower adherence to breast cancer screening guidelines, which may contribute to delayed diagnoses and reduced survival rates. These disparities are often influenced by limited access to quality healthcare and persistent inequities faced within Michigan. With Detroit's population being 77% AA, examining studies focused on the experiences of Black women within urban healthcare networks is essential to understanding the connections between demographic, socioeconomic factors, and breast cancer outcomes. To assess these studies, a literature search was conducted using Ovid Medline yielding 24 associated articles.

Mammogram rates among AA women in Detroit remain low, reflecting a complex …


Intercellular Mitochondrial Transfer Contributes To Microenvironmental Redirection Of Cancer Cell Fate, Julie Sofie Bjerring, Yara Khodour, Emilee Anne Peterson, Patrick Christian Sachs, Robert David Bruno Jan 2025

Intercellular Mitochondrial Transfer Contributes To Microenvironmental Redirection Of Cancer Cell Fate, Julie Sofie Bjerring, Yara Khodour, Emilee Anne Peterson, Patrick Christian Sachs, Robert David Bruno

School of Medical Diagnostics & Translational Sciences Publications

The mammary microenvironment has been shown to suppress tumor progression by redirecting cancer cells to adopt a normal mammary epithelial progenitor fate in vivo. However, the mechanism(s) by which this alteration occurs has yet to be defined. Here, we test the hypothesis that mitochondrial transfer from normal mammary epithelial cells to breast cancer cells plays a role in this redirection process. We evaluate mitochondrial transfer in 2D and 3D organoids using our unique 3D bioprinting system to produce chimeric organoids containing normal and cancer cells. We demonstrate that breast cancer tumoroid growth is hindered following interaction with mammary epithelial cells …


Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank Shekhar Rai, Muhammad Imran Sajid, Jonathan Moreno, Keykavous Parang, Rakesh Kumar Tiwari Aug 2024

Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank Shekhar Rai, Muhammad Imran Sajid, Jonathan Moreno, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum …


Proteomic Characterization And Cytotoxic Potential Of Proteins From Cuscuta (Cuscuta Epithymum (L.) Crude Herbal Product Against Mcf-7 Human Breast Cancer Cell Line, Umaima Akhtar, Yamna Khurshid, Bishoy El-Aarag, Basir Syed, Ishtiaq A. Khan, Keykavous Parang, Aftab Ahmed May 2024

Proteomic Characterization And Cytotoxic Potential Of Proteins From Cuscuta (Cuscuta Epithymum (L.) Crude Herbal Product Against Mcf-7 Human Breast Cancer Cell Line, Umaima Akhtar, Yamna Khurshid, Bishoy El-Aarag, Basir Syed, Ishtiaq A. Khan, Keykavous Parang, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

The burden of breast cancer, the second leading cause of death worldwide, is increasing at an alarming rate. Cuscuta, used in traditional medicine for different ailments, including cancer, is known for containing phytochemicals that exhibit anticancer activity; however, the bioactivities of proteins from this plant remain unexplored. This study aimed to screen the cytotoxic potential of proteins from the crude herbal product of Cuscuta epithymum(L.) (CE) harvested from the host plants Alhagi maurorum and Medicago sativa.

Methods

The proteins from CE were extracted using a salting-out method, followed by fractionation with a gel filtration chromatography column. Gel-free shotgun …


Harnessing Exosomes As A Platform For Drug Delivery In Breast Cancer: A Systematic Review For In Vivo And In Vitro Studies, Abdulwahab Teflischi Gharavi, Saeed Irian, Azadeh Niknejad, Keykavous Parang, Mona Salimi Apr 2024

Harnessing Exosomes As A Platform For Drug Delivery In Breast Cancer: A Systematic Review For In Vivo And In Vitro Studies, Abdulwahab Teflischi Gharavi, Saeed Irian, Azadeh Niknejad, Keykavous Parang, Mona Salimi

Pharmacy Faculty Articles and Research

Breast cancer remains a significant global health concern, emphasizing the critical need for effective treatment strategies, especially targeted therapies. This systematic review summarizes the findings from in vitro and in vivo studies regarding the therapeutic potential of exosomes as drug delivery platforms in the field of breast cancer treatment. A comprehensive search was conducted across bibliographic datasets, including Web of Science, PubMed, and Scopus, using relevant queries from several related published articles and the Medical Subject Headings Database. Then, all morphological, biomechanical, histopathological, and cellular-molecular outcomes were systematically collected. A total of 30 studies were identified based on the Preferred …


Diosgenin Prevents Breast Cancer Metastasis Via The Inhibition Of Epithelial-Mesenchymal Transition., Santosh K. Singh, Rajesh Singh Mar 2024

Diosgenin Prevents Breast Cancer Metastasis Via The Inhibition Of Epithelial-Mesenchymal Transition., Santosh K. Singh, Rajesh Singh

Research Symposium

Background: Globally, breast cancer (BrCa) is the primary cause of cancer-related morbidity and death in women. Despite significant changes in healthcare activities like screening and early detection over the past few decades, African Americans (AA) continue to experience cancer health disparities. Many studies have been done on BrCa treatments, but AA patients have had less success than other racial or ethnic groups. Therefore, novel strategies are required to improve survival rates, lower BrCa mortality, and ultimately enhance the health of racial/ethnic minorities. Current treatment regimens, such as chemotherapeutic agents, are showing less effectiveness since they are linked to drug resistance, …


Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad Feb 2024

Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad

Dissertations, Theses, and Capstone Projects

The overexpression of HER2 accounts for 20-30% of breast cancer tumors and not only serves as a marker for poor predictive clinical outcomes but also as a target for treatment. Antibody-drug conjugates (ADCs) combine the selectivity of monoclonal antibodies (mAbs) with the efficacy of chemotherapeutic drugs to provide targeted treatment without toxicity to normal tissue. Most of the ADCs currently in the clinic for cancer chemotherapy are based on complex organic molecules. In contrast, the conjugation of metallodrugs to mAbs has been overlooked when there is enormous potential in this area with the resurgence of metal-based drugs as prospective cancer …


A Cyclin D1 Intrinsically Disordered Domain Accesses Modified Histone Motifs To Govern Gene Transcription, Xuanmao Jiao, Gabriele Di Sante, Mathew Casimiro, Agnes Tantos, Anthony Ashton, Zhiping Li, Yen Quach, Dharmendra Bhargava, Agnese Di Rocco, Claudia Pupo, Marco Crosariol, Tamas Lazar, Peter Tompa, Chenguang Wang, Zuoren Yu, Zhao Zhang, Kawthar Aldaaysi, Ratna Vadlamudi, Monica Mann, Emmanuel Skordalakes, Andrew Kossenkov, Yanming Du, Richard Pestell Jan 2024

A Cyclin D1 Intrinsically Disordered Domain Accesses Modified Histone Motifs To Govern Gene Transcription, Xuanmao Jiao, Gabriele Di Sante, Mathew Casimiro, Agnes Tantos, Anthony Ashton, Zhiping Li, Yen Quach, Dharmendra Bhargava, Agnese Di Rocco, Claudia Pupo, Marco Crosariol, Tamas Lazar, Peter Tompa, Chenguang Wang, Zuoren Yu, Zhao Zhang, Kawthar Aldaaysi, Ratna Vadlamudi, Monica Mann, Emmanuel Skordalakes, Andrew Kossenkov, Yanming Du, Richard Pestell

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The essential G1-cyclin, CCND1, is frequently overexpressed in cancer, contributing to tumorigenesis by driving cell-cycle progression. D-type cyclins are rate-limiting regulators of G1-S progression in mammalian cells via their ability to bind and activate CDK4 and CDK6. In addition, cyclin D1 conveys kinase-independent transcriptional functions of cyclin D1. Here we report that cyclin D1 associates with H2BS14 via an intrinsically disordered domain (IDD). The same region of cyclin D1 was necessary for the induction of aneuploidy, induction of the DNA damage response, cyclin D1-mediated recruitment into chromatin, and CIN gene transcription. In response to …


Pcbp1 Regulates Lifr Through Fam3c To Maintain Breast Cancer Stem Cell Self-Renewal And Invasiveness, William S. Streitfeld Nov 2023

Pcbp1 Regulates Lifr Through Fam3c To Maintain Breast Cancer Stem Cell Self-Renewal And Invasiveness, William S. Streitfeld

MUSC Theses and Dissertations

The poly(rC) binding protein 1 gene (PCBP1) encodes the heterogenous nuclear ribonucleoprotein E1 (hnRNPE1), a nucleic acid-binding protein that plays a tumor-suppressive role in mammary epithelial cells by regulating phenotypic plasticity and cell fate. Following the loss of PCBP1 function, the FAM3C gene (encoding the Interleukin-like EMT inducer, or “ILEI” protein) and the leukemia inhibitory factor receptor (LIFR) gene are upregulated. Interaction between FAM3C and LIFR in the extracellular space induces phosphorylation of signal transducer and activator of transcription 3 (pSTAT3). Overexpression and/or hyperactivity of STAT3 has been detected in 40% of breast cancer cases and is associated with a …


Immunepotent Crp Enhances Cyclophosphamide-Induced Cytotoxicity Through A Caspase Independent But Ros Dependent Mechanism In Triple Negative-Breast Cancer Cells, Ana L. Rivera, A. C. Martínez-Torres, C. Rodríguez-Padilla Sep 2023

Immunepotent Crp Enhances Cyclophosphamide-Induced Cytotoxicity Through A Caspase Independent But Ros Dependent Mechanism In Triple Negative-Breast Cancer Cells, Ana L. Rivera, A. C. Martínez-Torres, C. Rodríguez-Padilla

Research Symposium

Background: Breast cancer (BC) is one of the leading causes of cancer death worldwide. Cyclophosphamide (CYP) remains a mainstay in cancer therapy mainly in the triple negative breast cancer subtype (TNBC) in spite of harmful adverse effects and cell death-resistances. To face this, combination of chemotherapies and immunotherapies has been proposed. IMMUNEPOTENT CRP (ICRP) is an immunotherapy that has cytotoxic effects in several cancer cells without affecting peripheral blood mononuclear cells (PBMC) and CD3+ cells, beside improving clinical parameters of chemotherapy-treated patients. The aim of this study was to evaluate the mechanism of cytotoxicity induced by ICRP in combination with …


Pre-Clinical Evaluation Of A Potential Ruthenium-Based Chemotherapeutic Agent For The Treatment Of Triple Negative Breast Cancer, Nazia Nayeem Sep 2023

Pre-Clinical Evaluation Of A Potential Ruthenium-Based Chemotherapeutic Agent For The Treatment Of Triple Negative Breast Cancer, Nazia Nayeem

Dissertations, Theses, and Capstone Projects

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that represents roughly 15% of all diagnosed breast cancers. TNBC is defined by the absence of expression of progesterone, estrogen, and human epidermal growth factor 2 receptors, and has a higher incidence rate in pre-menopausal women and women of African and of Hispanic ancestry. Due to the inability to target a receptor, treatment is limited to nonspecific chemotherapy or immunotherapy. Only one FDA approved therapy is available specifically to treat TNBC, which is antibody drug conjugate Sacitzumab-govitecan, given to patients who have already gone through two rounds of …


Targeting Breast Cancer: The Familiar, The Emerging, And The Uncharted Territories, Hamidreza Montazeri Aliabadi, Arthur Manda, Riya Sidgal, Co Chung Aug 2023

Targeting Breast Cancer: The Familiar, The Emerging, And The Uncharted Territories, Hamidreza Montazeri Aliabadi, Arthur Manda, Riya Sidgal, Co Chung

Pharmacy Faculty Articles and Research

Breast cancer became the most diagnosed cancer in the world in 2020. Chemotherapy is still the leading clinical strategy in breast cancer treatment, followed by hormone therapy (mostly used in hormone receptor-positive types). However, with our ever-expanding knowledge of signaling pathways in cancer biology, new molecular targets are identified for potential novel molecularly targeted drugs in breast cancer treatment. While this has resulted in the approval of a few molecularly targeted drugs by the FDA (including drugs targeting immune checkpoints), a wide array of signaling pathways seem to be still underexplored. Also, while combinatorial treatments have become common practice in …


The Co-Oncogenic Function Of Ecdysoneless Protein With Erbb2 In Mammary Epithelial Cells, Benjamin B. Kennedy Aug 2023

The Co-Oncogenic Function Of Ecdysoneless Protein With Erbb2 In Mammary Epithelial Cells, Benjamin B. Kennedy

Theses & Dissertations

The Ecdysoneless (ECD) protein is highly evolutionarily conserved and ubiquitously expressed across human tissues. ECD has established roles in cell cycle regulation, embryogenesis, cell survival, and RNA biogenesis. ECD mRNA and protein are overexpressed in breast cancer, and its overexpression correlates with poor patient survival, especially in ErbB2/HER2-positive breast cancer. This thesis work investigates the co-oncogenic role of ECD in ErbB2-driven oncogenesis using immortalized mammary epithelial cells. Here, we show that ECD and ErbB2 overexpression in immortalized human mammary epithelial cells increases cancer traits, such as invasion, migration, and anchorage independent growth. Significantly, ECD+ErbB2 co-overexpression further enhanced all oncogenic traits. …


Parabens Promote Protumorigenic Effects In Luminal Breast Cancer Cell Lines With Diverse Genetic Ancestry, Jazma L. Tapia, Jillian C. Mcdonough, Emily L. Cauble, Cesar G. Gonzalez, Dede K. Teteh, Lindsey S. Treviño Jun 2023

Parabens Promote Protumorigenic Effects In Luminal Breast Cancer Cell Lines With Diverse Genetic Ancestry, Jazma L. Tapia, Jillian C. Mcdonough, Emily L. Cauble, Cesar G. Gonzalez, Dede K. Teteh, Lindsey S. Treviño

Health Sciences and Kinesiology Faculty Articles

Context

One in 8 women will develop breast cancer in their lifetime. Yet, the burden of disease is greater in Black women. Black women have a 40% higher mortality rate than White women, and a higher incidence of breast cancer at age 40 and younger. While the underlying cause of this disparity is multifactorial, exposure to endocrine disrupting chemicals (EDCs) in hair and other personal care products has been associated with an increased risk of breast cancer. Parabens are known EDCs that are commonly used as preservatives in hair and other personal care products, and Black women are disproportionately exposed …


Studying The Phosphorylation Of Isocitrate Dehydrogenase In Humans, Hannah Smith May 2023

Studying The Phosphorylation Of Isocitrate Dehydrogenase In Humans, Hannah Smith

Chemistry & Biochemistry Undergraduate Honors Theses

Isocitrate dehydrogenase is an important enzyme in the citric acid cycle where it catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate. While there are three isoforms of isocitrate dehydrogenase (IDH1, IDH2, and IDH3), this research will focus on IDH1. The phosphorylation of isocitrate dehydrogenase is a process that has been linked to the formation of both luminal-like and basal-like breast cancer. Despite these correlations, the mechanisms that cause breast cancer development are unknown. To examine this, an enzyme activity assay for each phosphorylation variant and crystallization were conducted. The results of these indicate that phosphorylation at each site (IDH1-T77, IDH1-S188, …


Mirna-489 Induces Immunogenic Cell Death In Triple Negative Breast Cancer Cells, Ryan P. Titus Apr 2023

Mirna-489 Induces Immunogenic Cell Death In Triple Negative Breast Cancer Cells, Ryan P. Titus

Senior Theses

It has been well established that microRNAs (miRNAs) play an important role in the regulation of gene expression and consequently promoting or downregulating molecular pathways. When dysregulated, miRNAs have been found to serve as important biomarkers for cancer diagnosis and influence tumor initiation and progression. It has been previously established that miRNA-489 is a tumor suppressor microRNA, and it directly targets cell proliferative pathways like the HER2-SHP2-MAPK pathway. In this study, we focus on the role of miRNA-489, in the induction of immunogenic cell death (ICD) in triple-negative breast cancer cell lines. We first examined the effects of miRNA-489 on …


Understanding The Implications Of Lineage Plasticity In Breast Cancer Evolution And Chemotherapy Response, Gadisti Aisha Mohamed Apr 2023

Understanding The Implications Of Lineage Plasticity In Breast Cancer Evolution And Chemotherapy Response, Gadisti Aisha Mohamed

Dartmouth College Ph.D Dissertations

Intra-tumoral heterogeneity and the presence of a phenotypically diverse cell population within a single tumor represents a major hurdle in the understanding of tumor progression and dynamics, and complicates the effective diagnosis and management of this disease. One of the ways by which tumors gain intra-tumoral variation is through the acquisition of phenotypic or lineage plasticity, whereby tumor cells evolve away from the lineage of origin and gain altered profiles. These alterations may impart specific survival benefits to different subpopulations of cells, enabling them to proliferate faster, migrate away from the site of the primary tumor or evade drug-induced elimination, …


Low Molecular Weight Cyclin E Deregulates Dna Replication And Damage Repair To Promote Genomic Instability In Breast Cancer, Mi Li Feb 2023

Low Molecular Weight Cyclin E Deregulates Dna Replication And Damage Repair To Promote Genomic Instability In Breast Cancer, Mi Li

Dissertations and Theses (Open Access)

Low molecular weight cyclin E (LMW-E) are oncogenic forms of cyclin E that are post translationally generated by neutrophil elastase (NE) mediated cleavage of the 50 KDa full-length cyclin E1 (FL-cycE, encoded by CCNE1gene). The resultant N-terminus deleted (40 amino acids) form of LMW-E is detected in breast cancer cells and tumor tissues, but not in normal mammary epithelial cells or adjacent normal tissues. Unlike FL-cycE, LMW-E drives mammary epithelial cell transformation in human cells and spontaneous mammary tumor formation in transgenic mouse models, but the oncogenic mechanisms of LMW-E and its unique function(s) independent of FL-cycE are not …


Pre-Clinical Trials With Precision-Medicine Based Therapeutics In Basal-Like Patient-Derived Xenografts, David C. Boyd Jan 2023

Pre-Clinical Trials With Precision-Medicine Based Therapeutics In Basal-Like Patient-Derived Xenografts, David C. Boyd

Theses and Dissertations

Breast cancer treatments have improved over time, but the diseases seeing the most benefit from these improvements have the estrogen receptor, progesterone receptor, or are positive for HER2. Basal-like breast cancer tends to not have these biomarkers, which necessitates their treatment to be traditional, untargeted therapeutics which are less effective and tend to have harsh adverse effect profiles – this is an important unmet need. These studies utilize a variety of techniques, including tissue culture, viability assays, high-throughput screening, in vivo drug treatments and imaging, pathway analyses, molecular techniques such as Western blot, antibody arrays, RNA sequencing, sc RNA sequencing, …


Kpt-330 Synergizes With Everolimus To Reduce Mtorc1-Overactive Basal-Like Triple-Negative Breast Cancer Brain Metastasis Burden, Aaron D. Valentine Jan 2023

Kpt-330 Synergizes With Everolimus To Reduce Mtorc1-Overactive Basal-Like Triple-Negative Breast Cancer Brain Metastasis Burden, Aaron D. Valentine

Theses and Dissertations

Triple-negative breast cancer (TNBC), a highly metastatic breast cancer subtype, accounts for approximately 20% of all breast cancer diagnoses. Basal-like TNBC is notably difficult to treat due to the lack of actionable drug targets such as estrogen and progesterone receptors, as well as HER2. Due to the deficiency in TNBC-targeting drugs that are able to cross the blood-brain barrier (BBB) for breast-to-brain metastasis, there is a need to develop novel BBB-permeable treatments. After preliminary testing, KPT-330 (XPO1 inhibitor) and everolimus (FKBP1A/mTOR inhibitor) were selected as drug candidates for this study. Patient-derived xenograft (PDX) models for in vitro and in vivo …


Integrin-Mediated Mechanotransduction Controls Activation Of Yap And Invasive Growth Of Breast Cancer, Xiaobo Wang Aug 2022

Integrin-Mediated Mechanotransduction Controls Activation Of Yap And Invasive Growth Of Breast Cancer, Xiaobo Wang

Dissertations and Theses (Open Access)

Tumor extracellular matrix (ECM) stiffness is correlated with the aggressiveness of breast cancer. Integrin-mediated adhesion and signaling are crucial for mammary tumorigenesis and tumor progression, in which focal adhesion kinase (FAK) - Src family kinases (SFKs) serves as a hub to relay the mechanical cues from the ECM. We have investigated the mechanisms through which integrin signaling controls mammary tumorigenesis and found that integrin-mediated mechanotransduction controls invasive growth of breast cancer cells in stiff matrices through activation of FAK and YAP. Mechanistic studies revealed that integrin signaling induces - via activation SFKs - tyrosine phosphorylation and inactivation of LATS1 and …


Low-Salt Diet Reduces Anti-Ctla4 Mediated Systemic Immune-Related Adverse Events While Retaining Therapeutic Efficacy Against Breast Cancer, Durga Khandekar, Debolanle O. Dahunsi, Isaac V. Manzanera Esteve, Sonya Reid, Jeffrey C. Rathmell, Jens M. Titze, Venkataswarup Tiriveedhi May 2022

Low-Salt Diet Reduces Anti-Ctla4 Mediated Systemic Immune-Related Adverse Events While Retaining Therapeutic Efficacy Against Breast Cancer, Durga Khandekar, Debolanle O. Dahunsi, Isaac V. Manzanera Esteve, Sonya Reid, Jeffrey C. Rathmell, Jens M. Titze, Venkataswarup Tiriveedhi

Biology Faculty Research

Immune checkpoint inhibitor (ICI) therapy has revolutionized the breast cancer treatment landscape. However, ICI-induced systemic inflammatory immune-related adverse events (irAE) remain a major clinical challenge. Previous studies in our laboratory and others have demonstrated that a high-salt (HS) diet induces inflammatory activation of CD4+T cells leading to anti-tumor responses. In our current communication, we analyzed the impact of dietary salt modification on therapeutic and systemic outcomes in breast-tumor-bearing mice following anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibody (mAb) based ICI therapy. As HS diet and anti-CTLA4 mAb both exert pro-inflammatory activation of CD4+T cells, we hypothesized that a combination of …


Endocrine-Disrupting Chemicals And Breast Cancer: Disparities In Exposure And Importance Of Research Inclusivity, Ashlie Santaliz Casiano, Annah Lee, Dede Teteh, Zeynep Madak Erdogan, Lindsey Trevino Mar 2022

Endocrine-Disrupting Chemicals And Breast Cancer: Disparities In Exposure And Importance Of Research Inclusivity, Ashlie Santaliz Casiano, Annah Lee, Dede Teteh, Zeynep Madak Erdogan, Lindsey Trevino

Health Sciences and Kinesiology Faculty Articles

Endocrine-disrupting chemicals (EDCs) are known contributors to breast cancer development. EDC exposures commonly occur through food packaging, cookware, fabrics, and personal care products as well as through the environment. Increasing evidence highlights disparities in EDC exposure across racial/ethnic groups, yet breast cancer research continues to lack the inclusion necessary to positively impact treatment response and overall survival in these socially disadvantaged populations. Additionally, the inequity in environmental exposures has yet to be remedied. Exposure to EDCs due to structural racism poses an unequivocal risk to marginalized communities. In this review, we summarize recent epidemiological and molecular studies on two lesser-studied …