Neoplasms Commons^™

Mirnas Signature As Potential Biomarkers For Cervical Precancerous Lesions In Human Papillomavirus Positive Women, Martha I. González-Ramírez, Yurley T. Cardona, María C. Agudelo, Carolina López, Juan J. Florez-Acosta, Samuel Agudelo-Gamboa, Jone Garai, Li Li, Carlos A. Orozco-Castaño, Jovanny Zabaleta, Gloria I. Sánchez

School of Medicine Faculty Publications

Biomarkers to identify women at risk of cervical cancer among those with high-risk HPV infection (hrHPV+) are needed. Deregulated expression of microRNAs (miRNAs) contributes to hrHPV-induced cervical carcinogenesis. We aimed at identifying miRNAs with the capacity to distinguish high (CIN2+) and low (≤ CIN1) grade cervical lesions. We sequenced miRNA libraries from Formalin-Fixed Paraffin-Embedded (FFPE) tissues from women with CIN2+ (n = 10) and age-matched women with ≤ CIN1 (n = 10), randomly and retrospectively selected from a trial that followed women for 24 months after a hrHPV+ test at the screening visit. Five miRNAs differentially expressed were validated by …

Her3-Targeted Therapeutic Antibodies And Antibody–Drug Conjugates In Non-Small Cell Lung Cancer Refractory To Egfr-Tyrosine Kinase Inhibitors, Margaret E. Larsen, Hui Lyu, Bolin Liu

School of Medicine Faculty Publications

Human epidermal growth factor receptor 3 (HER3) is a unique member of the human epidermal growth factor receptor (HER/EGFR) family, since it has negligible kinase activity. Therefore, HER3 must interact with a kinase-proficient receptor to form a heterodimer, leading to the activation of signaling cascades. Overexpression of HER3 is observed in various human cancers, including non-small cell lung cancer (NSCLC), and correlates with poor clinical outcomes in patients. Studies on the underlying mechanism demonstrate that HER3-initiated signaling promotes tumor metastasis and causes treatment failure in human cancers. Upregulation of HER3 is frequently observed in EGFR-mutant NSCLC treated with EGFR-tyrosine kinase …

Relative And Quantitative Characterization Of The Bovine Bacterial Ocular Surface Microbiome In The Context Of Suspected Ocular Squamous Cell Carcinoma, Hannah B. Gafen, Chin-Chi Liu, Nikole E. Ineck, Clare M. Scully, Melanie A. Mironovich, Lauren Guarneri, Christopher M. Taylor, Meng Luo, Marina L. Leis, Erin M. Scott, Renee T. Carter, Andrew C. Lewin

School of Medicine Faculty Publications

The ocular surface microbiome is altered in certain disease states. The aim of this study was to characterize the bovine bacterial ocular surface microbiome (BBOSM) in the context of ocular squamous cell carcinoma (OSCC). The conjunctiva of normal (n = 28) and OSCC (n = 10) eyes of cows aged 2 to 13 years from two farms in Louisiana and Wyoming were sampled using individual sterile swabs. DNA extraction followed by 16S ribosomal ribonucleic acid (rRNA) gene sequencing and real-time polymerase chain reaction (RT-PCR) were performed to, respectively, assess the relative and absolute BBOSM. Discriminant analysis (DA) was performed using …

Tumor Microenvironment As A Therapeutic Target In Melanoma Treatment, Naji Kharouf, Thomas W. Flanagan, Sofie Yasmin Hassan, Hosam Shalaby, Marla Khabaz, Sarah Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan

School of Graduate Studies Faculty Publications

The role of the tumor microenvironment in tumor growth and therapy has recently attracted more attention in research and drug development. The ability of the microenvironment to trigger tumor maintenance, progression, and resistance is the main cause for treatment failure and tumor relapse. Accumulated evidence indicates that the maintenance and progression of tumor cells is determined by components of the microenvironment, which include stromal cells (endothelial cells, fibroblasts, mesenchymal stem cells, and immune cells), extracellular matrix (ECM), and soluble molecules (chemokines, cytokines, growth factors, and extracellular vesicles). As a solid tumor, melanoma is not only a tumor mass of monolithic …

17Β-Estradiol Promotes Extracellular Vesicle Release And Selective Mirna Loading In Erα-Positive Breast Cancer, Rares Drula, Barbara Pardini, Xiao Fu, Mireia Cruz De Los Santos, Ancuta Jurj, Lan Pang, Sherien M El-Daly, Linda Fabris, Erik Knutsen, Mihnea P Dragomir, Recep Bayraktar, Yongfeng Li, Meng Chen, Filippo Del Vecchio, Léa Berland, Jessica Dae, Daniel Fan, Masayoshi Shimizu, Anh M Tran, Mercedes Barzi, Carlotta Pioppini, Angelica M Gutierrez, Cristina Ivan, Salyna Meas, Carolyn S Hall, Suresh K Alahari, Ioana Berindan-Neagoe, Muller Fabbri, Anthony Lucci, Banu Arun, Simone Anfossi, George A Calin

Faculty, Staff and Student Publications

The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor-positive (ER+) BC, we hypothesized that 17β-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17β-estradiol promote EV secretion specifically from ER+ BC cells via inhibition of miR-149-5p, hindering its regulatory activity on SP1, a transcription factor that regulates the EV biogenesis factor nSMase2. Additionally, miR-149-5p downregulation promotes hnRNPA1 expression, responsible for the loading of let-7's miRNAs into EVs. In multiple patient cohorts, …

Targeting Glutaminase Is Therapeutically Effective In Ibrutinib-Resistant Mantle Cell Lymphoma, Lingzhi Li, Lei Nie, Alexa Jordan, Qingsong Cai, Yang Liu, Yijing Li, Yuxuan Che, Jovanny Vargas, Zhihong Chen, Angela Leeming, Wei Wang, Yixin Yao, Michael Wang, Vivian Changying Jiang

Faculty, Staff and Student Publications

Mantle cell lymphoma (MCL) is an incurable B-cell non-Hodgkin lymphoma characterized by frequent relapses. The development of resistance to ibrutinib therapy remains a major challenge in MCL. We previously showed that glutaminolysis is associated with resistance to ibrutinib. In this study, we confirmed that glutaminase (GLS), the first enzyme in glutaminolysis, is overexpressed in ibrutinib-resistant MCL cells, and that its expression correlates well with elevated glutamine dependency and glutaminolysis. Furthermore, we discovered that GLS expression correlates with MYC expression and the functioning of the glutamine transporter ASCT2. Depletion of glutamine or GLS significantly reduced cell growth, while GLS overexpression enhanced …

5s Rrna Pseudogene Transcripts Are Associated With Interferon Production And Inflammatory Responses In Alcohol-Associated Hepatitis, Jianguo Wu, Adam Kim, Xiaoqin Wu, Semanti Ray, Daniela S Allende, Nicole Welch, Annette Bellar, Jaividhya Dasarathy, Srinivasan Dasarathy, Laura E Nagy

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Interferon (IFN) signaling is critical to the pathogenesis of alcohol-associated hepatitis (AH), yet the mechanisms for activation of this system are elusive. We hypothesize that host-derived 5S rRNA pseudogene (RNA5SP) transcripts regulate IFN production and modify immunity in AH.

APPROACH AND RESULTS: Mining of transcriptomic datasets revealed that in patients with severe alcohol-associated hepatitis (sAH), hepatic expression of genes regulated by IFNs was perturbed and gene sets involved in IFN production were enriched. RNA5SP transcripts were also increased and correlated with expression of type I IFNs. Interestingly, inflammatory mediators upregulated in sAH, but not in other liver …

Zinc Treatment Reverses And Anti-Zn-Regulated Mirs Suppress Esophageal Carcinomas In Vivo, Louise Fong, Kay Huebner, Ruiyan Jing, Karl Smalley, Christopher R Brydges, Oliver Fiehn, John Farber, Carlo M Croce

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Esophageal squamous cell carcinoma (ESCC) is a deadly disease with few prevention or treatment options. ESCC development in humans and rodents is associated with Zn deficiency (ZD), inflammation, and overexpression of oncogenic microRNAs: miR-31 and miR-21. In a ZD-promoted ESCC rat model with upregulation of these miRs, systemic antimiR-31 suppresses the miR-31-EGLN3/STK40-NF-κB-controlled inflammatory pathway and ESCC. In this model, systemic delivery of Zn-regulated antimiR-31, followed by antimiR-21, restored expression of tumor-suppressor proteins targeted by these specific miRs: STK40/EGLN3 (miR-31), PDCD4 (miR-21), suppressing inflammation, promoting apoptosis, and inhibiting ESCC development. Moreover, ESCC-bearing Zn-deficient (ZD) rats receiving Zn medication showed a 47% …

Review Of Gynaecological Cancer Among Aboriginal And/Or Torres Strait Islander People In Australia, Aime Powell, Ami Morseu-Diop, Maya Morton Ninomiya, Uday Narayan Yadav, Emily Phillips, Devendra Raj Singh, Tamara Butler, Emma Allanson, Lisa J. Whop

Journal of the Australian Indigenous HealthInfoNet

Gynaecological cancers bear a significant burden on the health of Australians. Whilst Australia has made great strides in reducing the overall gynaecological cancer burden nationally, Aboriginal and/or Torres Strait Islander women continue to experience disproportionately high rates of gynaecological cancers.

This review focuses on the social, cultural, and historical contexts that contribute to inequitable gynaecological cancer rates among Aboriginal and/or Torres Strait Islander women. An in-depth discussion on cervical cancer, ovarian cancer, and uterine cancer are described; including the incidence, mortality, survival, and management of these diseases for Aboriginal and/or Torres Strait Islander women.

It highlights both the persistent barriers …

Barriers To Colorectal Cancer Screening For Low-Income Hispanic Men In Urban Areas Between 50-75, Alex Vega

Rowan-Virtua Research Day

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. Although CRC screening rates have improved in non-Hispanic whites (NHW), Hispanic adult males (HAM) aged 50-75 in urban areas continue to experience low screening rates and higher CRC morbidity and mortality. This review aims to identify the barriers to CRC screening among HAM and propose targeted interventions to increase screening rates. A comprehensive literature review was conducted using databases such as PubMed, Scopus, and Google Scholar. Key search terms included "colorectal cancer", "screening", "Hispanic adult males", "urban", "barriers", and "interventions". Factors identified include poverty, language …

Cellular Metabolism Therapy Slowing Growth Rate Of Glioblastomas, Heet Patel

Rowan-Virtua Research Day

Glioblastoma Multiforme (GBM), more commonly known as glioblastomas, are a form of specialized brain tumors called gliomas. Glioblastomas most commonly occur in glial cells of the central nervous system and the average age of diagnosis is 64. Treatment methods implemented currently are surgery of the removable masses followed by courses of chemotherapy and radiotherapy. These methods can only prolong the life span by a few months and as such, new research focused on tumor cell metabolism is being conducted to determine its impact on the progression of this tumor. Tumor masses, such as Glioblastomas, modify their metabolism via the Warburg …

Evaluating The Effect Of A Taxane-Based Anti-Cancer Drug On The Adult Taste Organ Using A Mouse Model, Archana Kumari, Lucre'ce Estropia

Rowan-Virtua Research Day

Chemosensory alteration is one of the major side effects of chemotherapy that can negatively impact the quality of life of cancer patients. Decreased appetite and food aversions can consequently lead to substantial reductions in food intake and thereby malnutrition and poor patient outcomes. The chemotherapeutic agent, taxane (docetaxel), is an effective choice of treatment for breast cancer, gastric cancer, or prostate cancer. Despite its major effects as an anti-cancer medication, patients under taxane treatments have reported taste alterations. Essentially, the drug disrupts normal microtubule growth by inhibiting microtubule depolymerization. By binding to ß-tubulin, a major component of mitotic spindles, docetaxel …

Mcl-1 Inhibition Modulates Erk-Mediated Resistance In Multiple Myeloma, Omar Al-Odat, Krishne Gowda, Shantu Amin, Tulin Budak-Alpdogan, Subash Jonnalagadda, Manoj Pandey

Rowan-Virtua Research Day

Novel multiple myeloma (MM) treatments have significantly improved over the previous several decades, primarily on account of targeting bone marrow microenvironment (BMM) pathways. However, drug resistance and patient relapse remain major clinical problems. The role of BMM in the upregulation of anti-apoptotic protein Mcl-1 is well documented. The Mcl-1 protein plays a critical role in the progression and acquired drug resistance in MM. The regulation of Mcl-1, a protein characterized by a short half-life, from transcription to degradation is crucial for understanding its role in cell survival. The GSK3β and Erk play important role in the stability of Mcl-1. Also, …

The Clinical Definition And Characterization Of Field Of Cancerization In Patients With Actinic Keratoses, Stuti Prajapati, Christina Kontzias, Mallory Zaino, Steven Feldman

Rowan-Virtua Research Day

Introduction: Chronic UV radiation affects the entire area of skin exposed, leading to visible actinic keratoses (AK) and subclinical changes in the surrounding skin. AKs are hyperkeratotic lesions, with a 0.025-16% risk of transforming into squamous cell carcinoma (SCC).1 Cellular atypia around AKs is the field of cancerization (FOC). Topical AK therapies can treat the FOC, while destructive treatments address visible lesions. FDA-approved products may be approved for field sizes up to 25 cm2.1,2

Objective: To characterize the FOC and assess the correlation between the FOC and number of AKs.

Methods: 100 patients with AKs were recruited. FOC was defined …

Barriers To Dermatological Care In Patients Who Received Extensive Mohs Surgery - An In-Depth Qualitative Analysis, Stuti Prajapati, Mallory Zaino, Christina Kontzias, Laura Doerfler, Steven R. Feldman

Rowan-Virtua Research Day

Background: Dermatological care needs to be accessible for the elderly, but they face prominent challenges contributing to delays in diagnosis and treatment. Prolonged management of may lead to widespread cutaneous malignancies, necessitating extensive Mohs surgery.

Objective: To identify areas for early intervention in the geriatric population who have undergone extensive Mohs surgery.

Methods: We performed a qualitative study on 10 patients 65 years and older (68-91) from Atrium Health Wake Forest Baptist dermatology clinics between December 2022 and February 2023, who had extensive Mohs surgery (3 or more layers removed).

Results: Three major areas for potential intervention for cutaneous carcinoma …

The Effect Of Socioeconomic Status On Primary Care Access And Cancer Screening Rates, Seth Spicer, Liam Courtney, Alyssa Laguerta, Abdul Sanni-Adam, Bharathi Balaji

Rowan-Virtua Research Day

Background: Low cancer screening rates among specific demographics are major health issues that lead to disparities in health outcomes. Early cancer detection is crucial for cure; however, it is not well known how age, race, gender, primary care access, and socio-economic status affect cancer screening rates. This review discusses the importance of cancer screening and the factors that affect screening rates.

Purpose: The purpose of this paper is to investigate how access to primary care affects cancer screening rates, with consideration to age, race, socioeconomic status, and primary care access in order to improve screening rates in underserved populations.

Methods: …

Perioperative Ketamine Use For Post Mastectomy Pain, Alessia Cooney, Jaylyn Thompson, Naomi Watkins-Granville

Rowan-Virtua Research Day

PMPS is defined as chronic neuropathic pain following breast cancer procedures in the ipsilateral arm, chest wall, axilla or shoulder.1-3 Approximately 20 to 50% of post mastectomy patients suffer from Post Mastectomy Pain Syndrome (PMPS).1 With more than 3.8 million breast cancer survivors, due to advances in treatment, there is increased importance in findings ways to better manage the quality of life of breast cancer survivors.1,4 Ketamine induces analgesic effects through its non-competitive antagonism of NDMA receptors.5 Low doses of ketamine infusion (20–30 mg x h−1) have been shown to produce analgesia in neuropathic pain states with benefits lasting up …

Echinomycin As A Promising Therapeutic Agent Against Kshv-Related Malignancies, Jungang Chen, Zhen Lin, Jiao Song, Karlie Plaisance-Bonstaff, Jennifer James, Shengyu Mu, Steven R. Post, Lu Dai, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL), which preferentially arise in immunocompromised patients while lack of effective therapeutic options. Oncoproteins Myc and hypoxia-inducible factor-1α (HIF1α) have been found closely related to KSHV infection, replication and oncogenesis. However, the strategies of dual targeting these two oncoproteins have never been developed and tested for treatments of KSHV-related malignancies. In the current study, we report that treatment of echinomycin dramatically regresses cell growth both in vitro-cultured KSHV + tumor cells and in vivo KS or PEL xenograft mice models, …

In Vitro Characterization Of A Novel Murine Model Of Cancerous Progression, Steven D. Scahill, Kelly Jean Sherman, Jessie J. Guidry, Whitney Walkowski, Theresa Nguyen, Durwood B. Ray, David H. Jones, Harry J. Gould, Dennis Paul

School of Graduate Studies Faculty Publications

To evaluate a potentially valuable tool to study cancer progression and metastasis, we characterized a novel murine model composed of a parental oncogene-transformed embryonic fibroblast line and five cell lines isolated from progressively advanced tumors. Lines derived from distant metastases displayed significantly greater rates of motility, invasiveness, and extracellular acidification than lines derived from a primary tumor or local metastases. A comprehensive proteomic analysis of these cells showed numerous oncogenes to be upregulated and tumor suppressors to be downregulated in the advanced lines, and provided novel targets for future examination. The first cell line capable of extravasation displayed particularly high …

Tcf4 Is A Key Mediator Of Cell Identity And Oncogenesis In Neuroblastoma, Nour Aljouda

Theses and Dissertations (ETD)

Neuroblastomas (NB) are embryonal childhood tumors that derive from the multipotent neural crest cells (NCCs) of the peripheral nervous system. NB accounts for more than 15% of all childhood cancer-related deaths. Despite the most intensive multimodal therapy, more than 50% of patients with high-risk NB relapse with often fatal, resistant disease. Novel therapies are desperately needed to improve cure rates. Previous studies proposed that the deregulation of normal neural crest developmental programs contributes to NB oncogenesis by retaining the highly migratory and proliferative traits of NCCs. Thus, activation or repression of neural crest developmental pathways have been implicated in NB …