Life Sciences Commons^™

Mortaparibplus- A Novel Anticancer Small Molecule Abrogating Mortalin-P53 Interaction In Cancer Cells, Anissa N. Sari, Ahmed Elwakeel, Jaspreet K. Dhanjal, Vipul Kumar, Durai Sundar, Sunil C. Kaul, Renu Wadhwa

Research Symposium

Background. The cessation of tumor cell growth through cell cycle arrest and apoptosis is determined by p53, a tumor suppressor protein. However, the interaction between mortalin-p53 within cytoplasm/nucleus leads to the inactivation of p53 transcriptional activation function. The disruption of mortalin-p53 complex has been suggested as an approach for developing a potential anticancer drug.

Methods. A screening of a high-content chemical library was performed to determine a molecule with mortalin-p53-interaction disrupting characteristics. After four-rounds of visual assays, we discovered a triazole derivative (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole, named Mortaparib^Plus) with a potential ability of disrupting mortalin-p53-complex. In this study, we recruited …

National Survey On The Availability Of Oncology Palliative Care Services At Tertiary General And Cancer Hospitals In China, Xiaomei Li, Xin Shelley Wang, Haili Huang, Miao Liu, Yinan Wu, Jiaojiao Qiu, Boran Zhang, Linhong Cui, David Hui

Faculty, Staff and Student Publications

Background: This nationwide survey studied the level of palliative care (PC) access for Chinese patients with cancer among cancer care providers either in tertiary general hospitals or cancer hospitals in China.

Methods: Using a probability-proportionate-to-size method, we identified local tertiary general hospitals with oncology departments to match cancer hospitals at the same geographic area. A PC program leader or a designee at each hospital reported available PC services, including staffing, inpatient and outpatient services, education, and research, with most questions adapted from a previous national survey on PC. The primary outcome was availability of a PC service.

Results: Most responders …

Challenges In Genetic Counseling In Hereditary Cancer Syndromes In A Mexican Oncologic Center, Diana Cristina Perez-Ibave, Diana Cristina De Lourdes Perez Ibave, María Fernanda Noriega-Iriondo, Omar Alejandro Zayas-Villanueva, Fernando Alcorta-Nuñez, Juan Francisco González-Guerrero, Adelina Alcorta-Garza, David Hernandez-Barajas, Oscar Vidal-Gutierrez, Carlos Horacio Burciaga-Flores

Research Symposium

Background: In Mexico, hereditary cancer is underdiagnosed, medical geneticists give genetic counseling, but the access is limited due to the socio-economic characteristics of the population. The CUCC (Centro Universitario Contra el Cáncer) Early Cancer Detection Clinic (CECIL) created a model in which patients without cancer are enrolled in a prevention cancer screening program.

Methods: From 2016 to 2021, 3014 patients were enrolled in the prevention program. Patients were evaluated with a hereditary cancer risk survey before a consultation. Those with at least one familial hereditary risk positive answer were assessed in a consultation. We also included patients with cancer diagnoses …

Global Proteomic Identifies Multiple Cancer-Related Signaling Pathways Altered By A Gut Pathobiont Associated With Colorectal Cancer, Ewa Pasquereau-Kotula, Giulia Nigro, Florent Dingli, Damarys Loew, Patrick Poullet, Yi Xu, Scott Kopetz, Jennifer Davis, Lucie Peduto, Catherine Robbe-Masselot, Philippe Sansonetti, Patrick Trieu-Cuot, Shaynoor Dramsi

Faculty, Staff and Student Publications

In this work, we investigated the oncogenic role of Streptococcus gallolyticus subsp. gallolyticus (SGG), a gut bacterium associated with colorectal cancer (CRC). We showed that SGG UCN34 accelerates colon tumor development in a chemically induced CRC murine model. Full proteome and phosphoproteome analysis of murine colons chronically colonized by SGG UCN34 revealed that 164 proteins and 725 phosphorylation sites were differentially regulated. Ingenuity Pathway Analysis (IPA) indicates a pro-tumoral shift specifically induced by SGG UCN34, as ~ 90% of proteins and phosphoproteins identified were associated with digestive cancer. Comprehensive analysis of the altered phosphoproteins using ROMA software revealed up-regulation of …

Interleukin-10 In Cancer Immunotherapy: From Bench To Bedside, Mohamad Adham Salkeni, Aung Naing

Faculty, Staff and Student Publications

Interleukin (IL)-10 was one of the first cytokines to be recognized. However, its functionality in promoting antitumor immunity was described more recently. Context- and concentration-dependent biological effects are the hallmarks of the pleiotropic role of IL-10. Despite reducing tumor-promoting inflammation, IL-10 may have a role in rejuvenating exhausted tumor-resident T cells. Contrary to the assumption that IL-10 produces an immunosuppressive tumor microenvironment (TME), it promotes activation of tumor-resident CD8+ T cells, which aids tumor rejection. Emerging data from published early-Phase trials have shown mixed results in different tumor types. In this review, we summarize the biological effects of IL-10 and …

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 …

Carm1 Arginine Methyltransferase As A Therapeutic Target For Cancer, Margarida Santos, Jee Won Hwang, Mark T Bedford

Faculty, Staff and Student Publications

Coactivator-associated arginine methyltransferase 1 (CARM1) is an arginine methyltransferase that posttranslationally modifies proteins that regulate multiple levels of RNA production and processing. Its substrates include histones, transcription factors, coregulators of transcription, and splicing factors. CARM1 is overexpressed in many different cancer types, and often promotes transcription factor programs that are co-opted as drivers of the transformed cell state, a process known as transcription factor addiction. Targeting these oncogenic transcription factor pathways is difficult but could be addressed by removing the activity of the key coactivators on which they rely. CARM1 is ubiquitously expressed, and its KO is less detrimental in …

Construction And Performance Optimization Of Bioconjugated Nanosensors For Early Detection Of Breast Cancer And Pro-Inflammatory Diseases, Pooja Gaikwad

Dissertations, Theses, and Capstone Projects

In recent years, nanosensors have emerged as a tool with strong potential in medical diagnostics. Single-walled carbon nanotube (SWCNT) based optical nanosensors have notably garnered interest due to the unique characteristics of their near-infrared fluorescence emission, including tissue transparency, photostability, and various chiralities with discrete absorption and fluorescence emission bands. Additionally, the optoelectronic properties of SWCNT are sensitive to the surrounding environment, which makes them suitable for in vitro and in vivo biosensing. Single-stranded (ss) DNA-wrapped SWCNTs have been reported as optical nanosensors for cancers and metabolic diseases. Breast cancer and cardiovascular diseases are the most common causes of death …

Non-Coding Rnas: Foes Or Friends For Targeting Tumor Microenvironment, Anna Szymanowska, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Paola Amero

Faculty, Staff and Student Publications

Non-coding RNAs (ncRNAs) are a group of molecules critical for cell development and growth regulation. They are key regulators of important cellular pathways in the tumor microenvironment. To analyze ncRNAs in the tumor microenvironment, the use of RNA sequencing technology has revolutionized the field. The advancement of this technique has broadened our understanding of the molecular biology of cancer, presenting abundant possibilities for the exploration of novel biomarkers for cancer treatment. In this review, we will summarize recent achievements in understanding the complex role of ncRNA in the tumor microenvironment, we will report the latest studies on the tumor microenvironment …

Swarmdeepsurv: Swarm Intelligence Advances Deep Survival Network For Prognostic Radiomics Signatures In Four Solid Cancers, Qasem Al-Tashi, Maliazurina B Saad, Ajay Sheshadri, Carol C Wu, Joe Y Chang, Bissan Al-Lazikani, Christopher Gibbons, Natalie I Vokes, Jianjun Zhang, J Jack Lee, John V Heymach, David Jaffray, Seyedali Mirjalili, Jia Wu

Faculty, Staff and Student Publications

Survival models exist to study relationships between biomarkers and treatment effects. Deep learning-powered survival models supersede the classical Cox proportional hazards (CoxPH) model, but substantial performance drops were observed on high-dimensional features because of irrelevant/redundant information. To fill this gap, we proposed SwarmDeepSurv by integrating swarm intelligence algorithms with the deep survival model. Furthermore, four objective functions were designed to optimize prognostic prediction while regularizing selected feature numbers. When testing on multicenter sets (n = 1,058) of four different cancer types, SwarmDeepSurv was less prone to overfitting and achieved optimal patient risk stratification compared with popular survival modeling algorithms. Strikingly, …

Cancer: The Burden Of Treatments Eased By Recent Developments In The Field: A Review Of The Literature, Zachary J. Seim

Masters Projects

Cancer is a very prevalent disease that has affected most of the population. Treatment options that have been used for decades are beginning to be outcompeted by newer developments in the field. Newer developments allow a more specific response to cancers that have proven to be very difficult for traditional treatment. Immune specific treatments also give the ability to specifically target areas affected by the cancer, to reduce potential risk of systemic damage and autoimmunity. Developing cancer treatments that are highly specific brings forth a new age of medicine, hoping to prolong the life expectancy of those affected with cancers, …

The Roles Of Estrogen Receptor Alpha-Interacting Rnas And Exosomes In Breast Cancer, And E-Cadherin In Carcinomas, Brihget Catalina Sicairos-Meza

Graduate Theses and Dissertations

Carcinomas are malignancies of epithelial cells and account for >80% of cancer-related deaths. Approximately 75% of breast cancers express estrogen receptor alpha (ERα). ERα promotes breast cancer progression by enhancing cancer cell proliferation. Tamoxifen is commonly used to treat ERα-positive breast cancers but can result in endocrine therapy resistance. The mechanisms underlying endocrine therapy resistance remain elusive. The Du lab recently found that ERα is an RNA-binding protein. However, the significance of the ERα-RNA interaction is unknown. We fractionated ERα-positive MCF7 cells into cytoplasmic and nuclear fractions, followed by immunoprecipitation of ERα with associated RNAs and RNA-sequencing. We identified many …

Barriers And Determinants Of Consistent Offering Of Hpv Vaccination By Healthcare Facilities, Ikponmwosa Osaghae, Onyema Greg Chido-Amajuoyi, Banda A A Khalifa, Sanjay Shete

Faculty, Staff and Student Publications

Expanding access to HPV vaccination is critical to increasing HPV vaccine uptake. We assessed the determinants and barriers to consistent offering of HPV vaccine among healthcare facilities. This was a cross-sectional survey of healthcare providers (HCPs) in Texas. Prevalence of the reasons healthcare practices do not consistently offer HPV vaccination was estimated. Multivariable regression analyses were conducted. Of 1169 HCPs included in the study, 47.5% (95% CI: 44.6-50.3%) reported their practices do not provide HPV vaccination or do not offer it consistently. Compared to physicians, nurses had 77% lower odds (Adjusted Odds Ratio (AOR): 0.23, 95% CI: 0.16-0.32, p-value: < .001), and physician assistants had 89% lower odds (AOR: 0.11, 95% CI: 0.07-0.16, p-value: < .001) of their healthcare practices consistently offering HPV vaccination. Compared to university/teaching hospitals, the odds of healthcare practices consistently offering HPV vaccination were 44% lower (AOR: 0.56, 95% CI: 0.35-0.91, p-value: 0.019) in solo practices but 266% higher (AOR: 3.66, 95% CI: 2.04-6.58, p-value: < .001) in FQHC/public facilities. The common reasons healthcare practices do not consistently offer HPV vaccination were; HPV vaccination is not within the scope of the practice (48.1%), referrals to other clinics (27.7%), and limited personnel (11.4%). Non-physicians were more likely to report that HPV vaccination was not in their scope and to refer patients than physicians. Moreover, solo practices were more likely to report challenges with acquisition and storage of the vaccine and referral of patients as reasons for not consistently offering HPV vaccination than university/teaching hospitals, FQHC/public facilities, or group practices. System-level interventions including training of non-physicians and expansion of practice enrollment in programs that support HPV vaccine acquisition and storage are needed.

Neuro-Immune Interactions And Immuno-Oncology, Narmina Khanmammadova, Shajedul Islam, Padmanee Sharma, Moran Amit

Faculty, Staff and Student Publications

The nervous system is an important component of the tumor microenvironment (TME), driving tumorigenesis and tumor progression. Neuronal cues (e.g., neurotransmitters and neuropeptides) in the TME cause phenotypic changes in immune cells, such as increased exhaustion and inhibition of effector cells, which promote immune evasion and cancer progression. Two types of immune regulation by tumor-associated nerves are discussed in this review: regulation via neuronal stimuli (i.e., by neural transmission) and checkpoint-mediated neuronal immune regulation. The latter occurs via the expression of immune checkpoints on the membranes of intratumoral nerves and glial cells. Here, we summarize novel findings regarding the neuroimmune …

Early Stage Or Curable Cancer Diagnoses In Minorities: A Journey Of Survivors, Lora Asberry

Master of Science in Integrative Biology Theses

Patients diagnosed with early-staged or curable forms of cancer experience physical, as well as, mental challenges associated with disease progression and treatment. Previous studies have demonstrated that minorities and underrepresented communities did not receive the same level of care in comparison to their non-minority counterparts. Previous studies have also demonstrated that health disparities among minorities affected their cancer journey. This study addressed: how medical disparities varied between minorities and non-minorities, the overall effects of the cancer diagnoses in minorities compared to non-minorities, whether these perspectives differed in male vs. female participants, and whether there were any possible communication barriers between …

Lung And Colorectal Cancer Disparities In Appalachian Kentucky: Spatial Analysis On The Influence Of Education And Literacy, Nicole Robertson Mph, Todd Burus, Lauren Hudson, Pamela C. Hull, Lee Park, Nathan L. Vanderford

Markey Cancer Center Faculty Publications

Low educational attainment and high cancer incidence and mortality rates have long been a challenge in Appalachian Kentucky. Prior studies have reported disparities in cancer incidence and mortality between Appalachian and non-Appalachian populations, but the influence of education on this disparity has not been extensively studied. Herein, all cancers and two cancer sites with available screenings (colorectal and lung) were joined with education indicators (educational attainment and literacy) and one geographic indicator across all 120 Kentucky counties. This dataset was used to build choropleth maps and perform simple linear and spatial regression to assess statistical significance and to measure the …

Interferon Signaling Promotes Tolerance To Chromosomal Instability During Metastatic Evolution In Renal Cancer, Luigi Perelli, Federica Carbone, Li Zhang, Justin K Huang, Courtney Le, Hania Khan, Francesca Citron, Edoardo Del Poggetto, Tony Gutschner, Hideo Tomihara, Melinda Soeung, Rosalba Minelli, Sanjana Srinivasan, Michael Peoples, Truong Nguyen Anh Lam, Sebastian Lundgren, Ruohan Xia, Cihui Zhu, Alaa M T Mohamed, Jianhua Zhang, Kanishka Sircar, Alessandro Sgambato, Jianjun Gao, Eric Jonasch, Giulio F Draetta, Andrew Futreal, Ziad Bakouny, Eliezer M Van Allen, Toni Choueiri, Sabina Signoretti, Pavlos Msaouel, Kevin Litchfield, Samra Turajlic, Linghua Wang, Ying Bei Chen, Renzo G Di Natale, A Ari Hakimi, Virginia Giuliani, Timothy P Heffernan, Andrea Viale, Christopher A Bristow, Nizar M Tannir, Alessandro Carugo, Giannicola Genovese

Faculty, Staff and Student Publications

Molecular routes to metastatic dissemination are critical determinants of aggressive cancers. Through in vivo CRISPR-Cas9 genome editing, we generated somatic mosaic genetically engineered models that faithfully recapitulate metastatic renal tumors. Disruption of 9p21 locus is an evolutionary driver to systemic disease through the rapid acquisition of complex karyotypes in cancer cells. Cross-species analysis revealed that recurrent patterns of copy number variations, including 21q loss and dysregulation of the interferon pathway, are major drivers of metastatic potential. In vitro and in vivo genomic engineering, leveraging loss-of-function studies, along with a model of partial trisomy of chromosome 21q, demonstrated a dosage-dependent effect …

Characteristics, Treatment, And Outcome Of Diverticulitis After Immune Checkpoint Inhibitor Treatment In Patients With Malignancies, Austin R Thomas, Mostafa Eyada, Miho Kono, Krishnavathana Varatharajalu, Yang Lu, Guofan Xu, Kavea Panneerselvam, Malek Shatila, Mehmet Altan, Jennifer Wang, John A Thompson, Hao Chi Zhang, Muhammad Ali Khan, Gottumukkala S Raju, Anusha S Thomas, Yinghong Wang

Faculty, Staff and Student Publications

Purpose: Immune checkpoint inhibitors (ICIs) are efficacious for treating various malignancies. In addition to immune-related adverse events (irAEs), growing evidence suggests that ICIs might also be associated with diverticulitis. We aim to assess the clinical presentations and management of colonic diverticulitis among cancer patients after ICI treatment.

Methods: A retrospective study was conducted on ICI-treated adult cancer patients between 01/2010 and 06/2020. Patients were grouped based on when diverticulitis developed relative to ICI treatment, either before (controls) or after (cases). Patient clinical characters, treatment, and outcomes were compared between both groups.

Results: 77 eligible patients were included: 63 patients developed …

Normal Saline Remodels The Omentum And Stimulates Its Receptivity For Transcoelomic Metastasis, Hironari Akasaka, Wonjae Lee, Song Yi Ko, Ernst Lengyel, Honami Naora

Faculty, Staff and Student Publications

The omentum contains immune cell structures called milky spots that are niches for transcoelomic metastasis. It is difficult to remove the omentum completely, and there are no effective strategies to minimize the risk of colonization of preserved omental tissues by cancer cells that circulate in the peritoneal fluid. Normal saline is commonly administered into the peritoneal cavity for diagnostic and intraoperative lavage. Here we show that normal saline, when administered into the peritoneal cavity of mice, is prominently absorbed by the omentum, exfoliates its mesothelium, and induces expression of CX3CL1, the ligand for CX3CR1, within and surrounding the omental vasculature. …

Proteogenomic Landscape Of Gastric Adenocarcinoma Peritoneal Metastases, Shuangtao Zhao, Ruiping Wang, Shumei Song, Dapeng Hao, Guangchun Han, Xingzhi Song, Jianhua Zhang, Melissa Pool Pizzi, Namita Shanbhag, Andrew Futreal, Brian Badgwell, Kazuto Harada, George Calin, Jody Vykoukal, Chuan-Yih Yu, Hiroyuki Katayama, Samir M Hanash, Linghua Wang, Jaffer A Ajani

Faculty, Staff and Student Publications

Advanced gastric adenocarcinoma (GAC) often leads to peritoneal carcinomatosis (PC) and is associated with very poor outcome. Here we report the comprehensive proteogenomic study of ascites derived cells from a prospective GAC cohort (n = 26 patients with peritoneal carcinomatosis, PC). A total of 16,449 proteins were detected from whole cell extracts (TCEs). Unsupervised hierarchical clustering resulted in three distinct groups that reflected extent of enrichment in tumor cells. Integrated analysis revealed enriched biological pathways and notably, some druggable targets (cancer-testis antigens, kinases, and receptors) that could be exploited to develop effective therapies and/or tumor stratifications. Systematic comparison of expression …

Loss Of Ampkα2 Promotes Melanoma Tumor Growth And Brain Metastasis, Ping Yuan, Da Teng, Evelyn De Groot, Man Li, Sebastian Trousil, Che-Hung Shen, Jason Roszik, Michael A Davies, Y N Vashisht Gopal, Bin Zheng

Faculty, Staff and Student Publications

AMP-activated protein kinase (AMPK) is a critical cellular energy sensor at the interface of metabolism and cancer. However, the role of AMPK in carcinogenesis remains unclear. Here, through analysis of the TCGA melanoma dataset, we found that PRKAA2 gene that encodes the α2 subunit of AMPK is mutated in ∼9% of cutaneous melanomas, and these mutations tend to co-occur with NF1 mutations. Knockout of AMPKα2 promoted anchorage-independent growth of NF1-mutant melanoma cells, whereas ectopic expression of AMPKα2 inhibited their growth in soft agar assays. Moreover, loss of AMPKα2 accelerated tumor growth of NF1-mutant melanoma and enhanced their brain …

Atomistic Assessment Of Drug-Phospholipid Interactions Consequent To Cancer Treatment: A Study Of Anthracycline Cardiotoxicity, Yara Elsayed Ahmed

Theses and Dissertations

Despite being one of the most effective chemotherapeutic agents developed to date, Anthracyclines are notorious for their cardiotoxicity. Their clinical use is frequently limited both in dosage and in prescription due to the severe cardiac damage they cause. The mechanism of anthracycline-induced cardiotoxicity is not yet fully understood. However, it is hypothesized that interactions with the myocardial membrane play an important role in imparting cardiotoxicity. In this study, we use molecular dynamics simulations and density functional theory calculations to study the anthracycline drug molecules and the interactions that they have with the myocardial membrane. We construct a myocardial membrane model …

How ‘Bout Them Apples?: A Study On Antioxidants, Kylie Measom, Dr. Kim O'Neill

Journal of Undergraduate Research

They say “an apple a day keeps the doctor away.” Apples are laden with antioxidants which have been shown to prevent against cancer and other illnesses.¹ Antioxidants are molecules that prevent cancer by collecting excess free radicals in the body. Free radicals are highly reactive molecules. They may interfere with DNA and other biomolecules leading to DNA damage and mutations. Antioxidants prevent this by scavenging for free radicals before they can interact with other important biomolecules.² Apples, particularly the skins, have high phenolic content. Phenols are antioxidants that protect against oxidative damage caused by free radicals.³ Different …

The Integrative Studies On The Functional A-To-I Rna Editing Events In Human Cancers, Sijia Wu, Zhiwei Fan, Pora Kim, Liyu Huang, Xiaobo Zhou

Faculty, Staff and Student Publications

Adenosine-to-inosine (A-to-I) RNA editing, constituting nearly 90% of all RNA editing events in humans, has been reported to contribute to the tumorigenesis in diverse cancers. However, the comprehensive map for functional A-to-I RNA editing events in cancers is still insufficient. To fill this gap, we systematically and intensively analyzed multiple tumorigenic mechanisms of A-to-I RNA editing events in samples across 33 cancer types from The Cancer Genome Atlas. For individual candidate among ∼ 1,500,000 quantified RNA editing events, we performed diverse types of downstream functional annotations. Finally, we identified 24,236 potentially functional A-to-I RNA editing events, including the cases …

Precision Medicine Advancements In Glioblastoma: A Systematic Review, Karan Iyer, Shubham Saini, Suman Bhadra, Sohini Kulavi, Jaya Bandyopadhyay

BioMedicine

Background. Glioblastoma multiforme, commonly known as GBM or glioblastoma is a grade IV astrocytoma. Brain tumors are difficult to treat and lead to poor prognosis and survival in patients. Gliomas are categorized into four different grades among which GBM is the worst grade primary brain tumor with a survival of less than a year. The genomic heterogeneity of the brain tumor results in different profiles for patients diagnosed with glioblastoma. Precision medicine focuses on this specific tumor type and suggests specialized treatment for better prognosis and overall survival (OS). Purpose. With the recent advancements in Genome-Wide Studies (GWS) and various …

Synthesis, Characterization And Biological Evaluation Of Polyarginine Derived Bone-Targeting Peptides, Gina L. Antuono

Seton Hall University Dissertations and Theses (ETDs)

Osteoblast-targeting peptides in the treatment of bone disease is a new and novel approach to offering effective treatment of various cancers and can be used in bio-medical, medicinal chemistry and biotechnology applications. By targeting adhesion proteins produced by osteoblast cells, certain cancers which migrate and metastasize to the bone may be more effectively treated. An osteoblast-targeting peptide composed of Ser-Asp-Ser-Ser-Asp (SDSSD) which selectively binds to osteoblast cells via periostin has recently been identified. This peptide was functionalized with polyurethane, generating nanomicelles which encapsulated RNA for the therapeutic treatment of osteoporosis. This study has served as the basis for the research …

Understanding The Regulatory Context And Mechanism Of Hlh-25 Mediated Transcriptional Repression, Dagmawi Mamo

Masters Theses, 2020-current

The HES family of transcription factors are primarily repressors of transcription that play critical roles in mammalian embryogenesis by regulating cell differentiation and proliferation. Proper functioning of HES proteins is crucial in humans, as mutations or misexpression of HES1 is associated with lung, pancreas, colon, and other cancers. HES1 may mediate short-range or long-range repression through DNA-binding and or protein-protein interactions with other factors. However, prior genetic studies have not fully elucidated how the context-specific binding of HES1, or its C. elegans ortholog HLH-25, promotes the repression of transcription. Characterization of the cis-regulatory context and mechanism of HLH-25 mediated repression …

Development Of Combination Therapy Strategies To Treat Cancer Using Dihydroorotate Dehydrogenase Inhibitors, Nicholas Mullen

Theses & Dissertations

Cancer cells require supraphysiologic levels of nucleotide triphosphates to fuel their malignant behaviors, including uncontrolled proliferation, immune evasion, metastasis, and therapy resistance. This requirement is met by hyperactive flux through the de novo pyrimidine and de novo purine pathways. Dihydroorotate dehydrogenase (DHODH) is an essential enzyme in the de novo pyrimidine pathway that can be targeted by FDA approved and experimental drug compounds. A robust body of preclinical evidence, encompassing hundreds of independent studies over several decades, demonstrates impressive activity of DHODH inhibitors in animal models of cancer. Paradoxically, however, all clinical trials to date have failed to demonstrate efficacy …

Cannabidiol As A Synergist In Chemotherapy, Liam Pontes

Honors Program Theses and Projects

Cannabidiol (CBD) is a non-psychoactive compound commonly found in hemp and non-hemp plants. It has a molecular effect on cells, but its effect in modifying cellular signaling pathways has not been thoroughly tested until recently. Experimentation was done to determine whether CBD could induce cell death in MCF7 breast cancer cells. Both normal MCF7 cells and Cisplatin resistant MCF7 cells were used for these experiments. The cells were dosed with 0, 0.5, and 1.0 g/ml CBD dissolved in methanol. Later micrographs of the treated cells were collected and Annexin staining to determine the effect of CBD on cell death was …

Characterization Of Neutrophil Extracellular Traps In Naked Mole-Rats: A Step Towards Cancer Resistance, Thomas Abraham Smith

Undergraduate Honors Capstone Projects

Cancer is the second leading cause of death in the United States, exceeded only by heart disease. One of every five deaths in the United States is due to cancer. A growing area of research involves the analysis of cancer resistant traits in other species to understand their biological mechanisms and eventually make translations to human cancer research and clinical treatment. Because of their remarkable cancer resistance, the naked mole-rat (NMR) is a prime subject for this research, and various studies have already suggested that the immune mechanisms of the NMR might be harnessed for human cancer therapies^1-4,7. …