Cancer Biology Commons^™

Tak1 Blockade Plus Azacitidine Induces Apoptosis, Augments Cytarabine, And Ablates Clonogenicity In Mll-Af9+ Human Aml Cell Lines, Austin P. Runde, Cameron Lewis, Peter Breslin Sj, Jiwang Zhang

School of Medicine

Acute myeloid leukemia (AML) encompasses a diverse group of cancers that originate in the blood-forming tissues of the bone marrow [1]. Aside from the PML-RARA⁺ subtype, AML carries a 5-year survival rate of 28% for patients 20+ years of age. AML is the most common cancer of the hematopoietic system and is slightly more common in biological males; the average age at diagnosis is 68 years. Standard frontline treatment for AML is a two-phase regimen of intensive chemotherapy (CTx) employing daunorubicin and cytarabine; etoposide may also be added in select regimens. Despite 60-70% of patients achieving complete remission (CR), …

Mechanisms Of Extracellular Vesicle Uptake And Implications For The Design Of Cancer Therapeutics, Stephanie R Jackson Cullison, Joseph P Flemming, Kubra Karagoz, Peter J Wermuth, Mỹ G Mahoney

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The translation of pre-clinical anti-cancer therapies to regulatory approval has been promising, but slower than hoped. While innovative and effective treatments continue to achieve or seek approval, setbacks are often attributed to a lack of efficacy, failure to achieve clinical endpoints, and dose-limiting toxicities. Successful efforts have been characterized by the development of therapeutics designed to specifically deliver optimal and effective dosing to tumour cells while minimizing off-target toxicity. Much effort has been devoted to the rational design and application of synthetic nanoparticles to serve as targeted therapeutic delivery vehicles. Several challenges to the successful application of this modality as …

Identification Of New Leads Against Ubiquitin Specific Protease-7 (Usp7): A Step Towards The Potential Treatment Of Cancers, Sumaira Javaid, Seema Zadi, Muhammad Awais, Atai-Tul Wahab, Humaira Zafar, Innokentiy Maslennikov, M. Iqbal Choudhary

Pharmacy Faculty Articles and Research

Ubiquitin-specific protease-7 (USP7) is an important drug target as it regulates multiple proteins and genes (such as MDM2 and p53) with roles in cancer progression. Its inhibition can hinder the function of oncogenes, increase tumor suppression, and enhance immune response. The current study was designed to express USP7 in a prokaryotic system, followed by screening of small molecules against it using biophysical methods, primarily STD-NMR technique. Among them, 12 compounds showed interaction with USP7 as inferred from NMR-based screening. These compounds further caused destabilization of USP7 by reducing its melting temperature (T_m) up to 6 °C in …

Effects Of Cadherin Mediated Contact Normalization On Oncogenic Src Kinase Mediated Gene Expression And Protein Phosphorylation, Rachel E Nicoletto, Cayla J Holdcraft, Ariel C Yin, Edward P Retzbach, Stephanie A Sheehan, Amanda A Greenspan, Christopher M Laugier, Jason Trama, Caifeng Zhao, Haiyan Zheng, Gary S Goldberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Nontransformed cells form heterotypic cadherin junctions with adjacent transformed cells to inhibit tumor cell growth and motility. Transformed cells must override this form of growth control, called "contact normalization", to invade and metastasize during cancer progression. Heterocellular cadherin junctions between transformed and nontransformed cells are needed for this process. However, specific mechanisms downstream of cadherin signaling have not been clearly elucidated. Here, we utilized a β-catenin reporter construct to determine if contact normalization affects Wnt signaling in transformed cells. β-catenin driven GFP expression in Src transformed mouse embryonic cells was decreased when cultured with cadherin competent nontransformed cells compared to …

The Effects Of Cannabinoids On Migration-Related Protein Expression In Ewing’S Sarcoma, Allison Lashall

Theses

Ewing’s sarcoma is an aggressive pediatric bone cancer that has low five-year survival rates, primarily due to metastatic disease and resistance of recurring tumors to traditional treatment options; therefore, novel treatment options are needed. The compound cannabidiol (CBD) has been shown to reduce cell viability, migration, and invasion in several tumor types, though the cellular mechanism of action is not well understood. Our lab has demonstrated the ability of CBD to reduce viability, migration, and invasion of Ewing’s sarcoma cells in vitro and is investigating differential protein and cytokine expression of known mediators of migration, such as intercellular adhesion molecule …

Challenges And Coping Strategies Among Caregivers Of Children With Cancer Receiving Care At A National Referral Hospital In Kenya, Doris Machaki, Albanus Kyalo Mutisya, Jostine Mutinda, Sherry Oluchina, Samwel Maina Gatimu

School of Nursing & Midwifery, East Africa

Background: The number of children diagnosed with cancer is expected to increase by 2050. The caring aspect of these children is usually left to members of the family, more so the mothers. Caregivers are usually faced with various challenges, such as financial issues, social stigma, and emotional and psychological issues. Caregivers use various coping strategies to manage the challenges they experience in the caring process, which can be positive or negative coping strategies.

Objective: To explore the challenges and coping strategies of caregivers of children with cancer receiving care at a national referral hospital in Kenya.

Methods: This study employed …

Molecular Targets For Breast Cancer Therapy, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

"Breast cancer is by far the most common cancer in women, and for a while, it surpassed lung cancer as the most diagnosed cancer, regardless of gender, in 2020 [1]. Chemotherapy and hormone therapy are still the first line of treatment, despite extensive research in molecularly targeted drugs. Therefore, triple negative breast cancer (TNBC) is still known as the most challenging type for treatment due to the limited identified targets. Inherent and acquired resistance are still major hurdles in breast cancer therapy, which further highlights the importance of identifying new molecular targets in this battle. The inherent resistance of unresponsive …

Characterizing Biomolecular Structure Features Through An Innovative Elliptical Dichroism Spectrometry For Cancer Detection, Yusuf Asad, Keerthi Priya Jangili, Amara Arshad, Maliha Elma, Komila Rasuleva, Alfred Akinlalu, Tommy Gao, Umamaheswara Rao Tida, Wenjie Xia, Dali Sun

Electrical and Computer Engineering: Faculty Scholarship

This research introduces a novel method for evaluating the structural features of biomolecules, utilizing our innovative Elliptical Dichroism (ED) spectrometer specifically designed for stereochemical analysis. By integrating ED spectrometry with autocorrelation (AC) analysis, we investigate the conformational characteristics of biological molecules such as amino acids, proteins, and extracellular vesicles (EVs) induced by elliptically polarized UV absorption. Our streamlined approach offers a cost-effective and portable solution with minimal sample consumption and supports multiple working modes to efficiently characterize biomolecular structures. The insight from this new approach demonstrates potential applications in using biomolecular characterization for cancer detection.

Honey: A Natural Recipe For The Management Of Pancreatic Cancer, Aun A. Bangash, Muhammad A. Bangash, Georgina Villanueva, Haider Ahsan, Shiza Khan, Rida Shareef, Mudassier Ahmad, Dae J. Kim, Sahir S. Alvi, Bilal B. Hafeez

Research Colloquium

Background: Pancreatic cancer (PanCa) is the fourth deadliest cancer worldwide and expected to become the second deadliest cancer by 2030. In the USA, the National Cancer Institute put forth a grim prediction stating that there will be 64,050 new cases in 2023 alone and about 50,000 of these patients will die. The first line treatment for pancreatic cancer is Folfrinox, a three-drug regimen consisting of 5-Fluorouracil, irinotecan, and oxaliplatin. The second line treatment is gemcitabine combined with paclitaxel. Only 19% of patients who are prescribed the former regimen survive past 18 months of treatment while just 6% of patients survive …

Examination Of Oncogenic Effects Of Environmental Pollutants, Andrew Ackerman, Matthew Behling, Brock Earley, Janay Vacharasin

Journal of the South Carolina Academy of Science

Chemical byproducts produced by surrounding industrial complexes have polluted the local estuaries of Georgetown, South Carolina for several decades¹. Previous studies completed by the EPA and SCDNR showed that the estuaries contained carcinogenic pollutants released from the local manufacturing plants¹. One of the mentioned pollutants was dioxins which are produced during the paper bleaching process². Dioxins are highly toxic compounds that have various carcinogenic effects on the organisms that inhabit the area. These previous studies were conducted over thirty years ago. Therefore, a current study to determine if chemical byproducts are contaminating local estuaries …

Regulation Of P21 Function By A Sense Long Non-Coding Rna Generated By Alternative Polyadenylation, Anthony Ramadei

Dissertations, Theses, and Capstone Projects

As cells are continually undergoing damage to the genome, a coordinated change in gene expression across thousands of genes is required for the progression of the DNA damage response (DDR). After initial sensing of DNA damage, the transcription factor p53 induces expression of target genes to halt the cell-cycle to allow DNA repair and induce either senescence or apoptosis. One of the p53 target genes is CDKN1A which encodes the cyclin dependent kinase inhibitor p21. p21 halts cell-cycle progression in response to DNA damage and can also induce senescence. However, p21 expression in cancer cells undergoing chemotherapy allows survival by …

Combination Therapy Of Ido1 Inhibition And Anti-Pd1 Mediates Anti-Tumor Immunity By Promoting Memory Immunity Development And Cytotoxicity Of Γδ T And Nk Cells Via Il-2 Signaling And By Overcoming Pro-Tumor Effects Of Tgf-Β Signaling, Hyuk Jee

Dartmouth College Master’s Theses

Cutaneous melanoma is the most aggressive form of skin cancer even though it takes only about 1% of all skin cancers. Even among all cutaneous melanomas, NRAS-mutant melanoma is more aggressive than any other, and about 10-25% of all cutaneous melanoma cases have mutations in NRAS. NRAS is a member of the RAS family of proto-oncogenic GTPase proteins, and it plays a key role in signal transduction pathways responsible for cellular survival, proliferation, and metabolism. Immunotherapy is the first line of defense against NRAS-mutant melanoma because, despite tremendous efforts made for decades, it has not been successful to develop small …

Emerin Deficiency Drives Mcf7 Cells To An Invasive Phenotype, Emily Hansen, Christal Rolling, Matthew Wang, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer …

Role Of Kindlin 2 In Prostate Cancer, Katarzyna Bialkowska, Lamyae El Khalki, Priyanka Rana, Wei Wang, Daniel Lindner, Yvonne Parker, Lucia Languino, Dario Altieri, Elzbieta Pluskota, Khalid Sossey-Alaoui, Edward Plow

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Kindlin-2 is a cytoskeletal adapter protein that is present in many different cell types. By virtue of its interaction with multiple binding partners, Kindlin-2 intercalates into numerous signaling pathways and cytoskeletal nodes. A specific interaction of Kindlin-2 that is of paramount importance in many cellular responses is its direct binding to the cytoplasmic tails of integrins, an interaction that controls many of the adhesive, migratory and signaling responses mediated by members of the integrin family of cell-surface heterodimers. Kindlin-2 is highly expressed in many cancers and is particularly prominent in prostate cancer cells. CRISPR/cas9 was used as a primary approach …

Bp1003 Decreases Stat3 Expression And Its Pro-Tumorigenic Functions In Solid Tumors And The Tumor Microenvironment, Maria Gagliardi, Rhonda Kean, Bingbing Dai, Jithesh Augustine, Michael Roberts, Jason Fleming, D. Craig Hooper, Ana Ashizawa

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Overexpression and aberrant activation of signal transducer and activator of transcription 3 (STAT3) contribute to tumorigenesis, drug resistance, and tumor-immune evasion, making it a potential cancer therapeutic target. BP1003 is a neutral liposome incorporated with a nuclease-resistant P-ethoxy antisense oligodeoxynucleotide (ASO) targeting the STAT3 mRNA. Its unique design enhances BP1003 stability, cellular uptake, and target affinity. BP1003 efficiently reduces STAT3 expression and enhances the sensitivity of breast cancer cells (HER2⁺, triple negative) and ovarian cancer cells (late stage, invasive ovarian cancer) to paclitaxel and 5-fluorouracil (5-FU) in both 2D and 3D cell cultures. Similarly, ex vivo and in …

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 …

In-House Polydimethylsiloxane Microfluidic Device On Single Cell Trapping And Culturing Of Leukemia Cell Line: Comparison Between Conventional And Conventional With Centrifugal Methods, Alongkorn Pimpin, Sudchaya Bhanpattanakul, Tepparit Wongpakham, Chomkwan Tawatcharaporn, Thanawit Siha-Umphai, Mookdapa Sinsiriphan, Atikan Chalermchuang, Tewan Tongmanee, Attawut Thanomsridetchai, Thammawit Suwannaphan, Witsaroot Sripumkhaie, Pattaraluck Pattamang, Mayuree Chanasakulniyom, Praprudee Piyaviriyakul, Wutthinun Jeamsaksiri, Achariya Sailasuta, Theerawat Tharasanit, Theerayuth Kaewamatawong

The Thai Journal of Veterinary Medicine

To develop a suitable model to study biological and characterization of Cancer stem cells (CSCs), single cell trapping and culturing using microfluidic techniques have become a high-through put system that can manage and control microenvironment and practical intracellular analysis. The aim of this study was to develop and validate a microfluidic device for single cell trapping and culturing using the leukemia cell line as a cell model. Comparison between conventional and conventional with centrifugal methods was also analyzed. To compare trapping efficacy between these 2 methods, leukemia cell concentration of 1.5×106 cells/ml was loaded with a flow rate of 0.25 …

Dying Right: Supporting Anti-Cancer Therapy Through Immunogenic Cell Death, Elizabeth Schmitz

Theses & Dissertations

The primary goal of most anti-cancer therapy is to eradicate neoplastic cells. Simultaneously, neoplastic cell death is the first step of the cancer-immunity cycle, which starts with the release of antigens from cancer cells and ends with T-cell directed killing of cancer cells, in addition to long-standing memory to tumor antigens encountered. Immunogenic damage-associated-molecular patterns (DAMPs) are endogenous cell molecules repurposed in times of insurmountable cell stress (e.g., CALR, ATP, HMGB1) to facilitate communication between dying cells and adaptive immune cells, acting as adjuvants for the cancer-immunity cycle, in a cellular fate termed immunogenic cell death (ICD). It …

Targeting Ksr1 To Inhibit Stemness And Therapy Resistance, Heidi M. Vieira

Theses & Dissertations

Tumor heterogeneity is an important contributor to therapy resistance and relapse. Within the tumor, there are subpopulations of tumorigenic, self-renewing cells with enhanced clonogenicity and chemoresistance, termed tumor-initiating cells (TICs). Despite their importance in treatment response, there are no effective therapies to target TICs in solid tumors.

This study identifies a novel role for Kinase Suppressor of Ras 1 (KSR1) in regulating TICs and therapy resistance in Ras-driven cancers. KSR1 is a molecular scaffold in the Raf/MEK/ERK kinase cascade downstream of Ras. KSR1 is necessary for Ras-mediated transformation, but dispensable for normal cell growth; further, ksr1^-/- mice are phenotypically …

Chemotherapy-Induced Modulation Of Tumor Antigen Presentation, Alaina C. Larson

Theses & Dissertations

Pancreatic cancer is a lethal malignancy, with a five-year overall survival rate of just 13%. Current treatment approaches thus require modification and attention has shifted towards improving immunotherapy efficacy. Select chemotherapy drugs possess inherent immunomodulatory activity and could be used to initiate immunotherapeutic success, thereby restoring anti-tumor immunity in pancreatic cancer. In this work, I evaluated the impact of the chemotherapy drug gemcitabine on tumor antigen presentation by human leukocyte antigen class I (HLA-I). Gemcitabine regulated HLA-I expression on multiple levels, increasing pancreatic cancer cells’ HLA-I mRNA transcripts, total protein and surface expression, as well as surface stability. Temperature-dependent assay …