Cancer Biology Commons^™

Cytotoxic Activity Of Salvia Officinalis Extract Mediated By The Inhibition Of Jak2 In Breast Cancer, Salma Alawadi Dawood

Theses and Dissertations

Background: Breast cancer is the most common type of invasive cancer in women in their forties and fifties. Recent evidence suggests that JAK2/STAT3 signaling is constitutively active in breast cancer. Previous studies suggest that plant extracts, including Salvia Officinalis, have strong cytotoxic effects on breast cancer cells. The differential expression of miRNAs is also strongly linked to cancer development.

Aim: In the current study, we hypothesize that S. Officinalis extract suppresses JAK2 expression and has strong anticancer potential in MCF7 breast cancer cell lines.

Methods: GC-MS analysis showed the presence of flavonoids in dried leaf of …

Analysis Of Macrophage Migration Inhibitory Factor Genotype In Hemophilia A Patients, Murtadha Ali Hadi, Wijdan Nazar Ibrahim, Meaad Kadhum Hassan

Hematology/Oncology and Stem Cell Therapy

Background Hemophilia A, an X-linked bleeding disorder, is caused by a complete or partial deficiency in Factor VIII. Multiple factors play a role in the development and progression of bleeding episodes, especially arthropathy, in hemophilia patients. Objectives Detection of macrophage migration inhibitory factor (MIF)-173 G/C polymorphism in people with hemophilia A (PWH) and the possible associations between the type of MIF gene polymorphism and selected disease-related variables. Subjects and Methods This case–control study included 95 male patients aged 2 months to 63 years with hemophilia A and 95 nonhemophiliac subjects matched for age and sex. Allele-specific polymerase chain reaction (AS-PCR) …

Oncotypedx Testing Does Not Benefit Patients With Grade 1, Estrogen And Progesterone Receptor Positive Breast Cancers: A Tailorx Validated Study, Udai S. Sibia, W. Charles Mylander, Tasha Martin, Martin Rosman, Thomas J. Sanders, Young Lee, Lorraine Tafra, Rubie S. Jackson

Hematology/Oncology and Stem Cell Therapy

Background & Objectives We previously described a predictive AAMC model that identifies patients (grade 1, hormone positive) who would not benefit from OncotypeDX testing. The purpose of this study was to validate the AAMC model by assessing distant recurrence-free interval (DRFI) and invasive disease-free survival (IDFS) using TAILORx clinical trial data. Materials & Methods We retrospectively analyzed TAILORx trial data and categorized patients based on the AAMC model. AAMC low-risk patients are those with grade 1 and hormone positive tumors. Kaplan-Meier curves examined DRFI and IDFS. Results Of the total 9195 cases, 2246 (24.4%) were identified as AAMC low-risk. Among …

Post Autologous Hematopoietic Cell Transplant Care In The “Home Sweet Home” Setting: A Treatment Paradigm Shift, Mohamed A. Kharfan-Dabaja, Vivek Roy, Hemant Murthy, Deborah Fischer, Razan Mohty, Ashley Greathouse, Alethea Brown, Kathryn Moreno, Emily Godsey, Jennifer M. Higginbotham, Ashley Bartholomew, Alexis Jackson, Ricardo A. Torres-Guzman, Antonio J. Forte, Sikander Ailawadhi, Roxana Dronca, Michael Maniaci

Hematology/Oncology and Stem Cell Therapy

Multiple myeloma (MM) is the second most common hematologic malignancy with 34,470 estimated new cases in 2022. High-dose therapy followed by autologous hematopoietic cell transplantation (auto-HCT) is a standard treatment for MM even in the era of novel therapies. This is usually done in hospital-based setting, whether in the inpatient or outpatient units. Advanced Care at Home (ACH) represents a virtual hybrid hospital-at-home program that combines a virtual provider-staffed command center with vendor-mediated supply chain capable of delivering high-acuity care in the comfort of patient’s own homes. In our program, we leveraged the existing ACH platform to deliver post-HCT care …

Cytogenetically Normal Acute Myeloid Leukaemia At A Single Centre In South Africa, Nicholas Jenkins, Lee-Ann Phillips, Marian Stone, Estelle Verburgh, Jenna Oosthuizen, Karen Shires

Hematology/Oncology and Stem Cell Therapy

Background: The heterogeneous molecular landscape of cytogenetically normal acute myeloid leukaemia (CN-AML) renders it an ongoing therapeutic challenge. The European Leukaemia Net 2017 guidelines attempted to address this by guiding post-remission therapy according to six prognostically informative mutations. However, its applicability in a South African setting remains elusive due to limited local data. Objectives: This retrospective study aimed to describe a South African CN-AML cohort according to clinicopathological, molecular and treatment outcomes and consequently investigate the local applicability of a triple-mutation testing approach for risk stratification in accordance with the ELN 2017 guidelines, using nucleophosmin (NPM1), fms-like tyrosine kinase internal …

Peritoneal And Pleural Drains In Pediatric Hematopoietic Cell Transplant Recipients With Veno-Occlusive Disease Are Safe And Do Not Adversely Impact Clinical Outcomes, Hemalatha G. Rangarajan, Vinita B Pai Pharm, Joseph R. Stanek, Cassandra Rush Pharm, Jeffrey Naples, Misti Drope, Veronika Polishchuk, Rolla Abu Arja, Rajinder Ps Bajwa

Hematology/Oncology and Stem Cell Therapy

There is a lack of data on the safety and efficacy of peritoneal drain (PD) and chest tube (CT) in the management of effusions in stem cell transplant recipients with veno-occlusive disease (VOD). In this retrospective pediatric study we compared the clinical outcomes and health resource utilization (HRU) in 32 patients with VOD who had a PD placed (PD+) post HCT with 27 patients who did not (PD-). Nine patients had a CT (7 PD+ and 2 PD-). PD+ patients were more likely than PD- patients to have received myeloablative conditioning (100% vs 85.2%; p=0.04) and have severe or very …

Post-Transplantation Cyclophosphamide Based Graft-Versus-Host-Disease Prophylaxis Compared To Methotrexate-Cyclosporine A In Matched Related Allogeneic Hematopoietic Stem Cell Transplantation, Mohamed Shouman, Osman Mansour, Mosaad M. El Gammal, Raafat Abdel-Fattah, Mohamed A. Samra, Alaa El Haddad, Mohamed Maher, Hossam K. Mahmoud

Hematology/Oncology and Stem Cell Therapy

Background: Post-transplant cyclophosphamide (PTCy) has shown promising results with low rates of severe graft-versus-host-disease (GVHD), either alone or combined with conventional immunosuppression (CIS). However, studies comparing PTCy with CIS as a GVHD prophylaxis are scarce.

Objective: The study aimed to evaluate the rates of GVHD and survival outcomes in patients undergoing peripheral blood stem cell transplant (PBSCT) from HLA matched related donors (MRD) receiving PTCy based GVHD prophylaxis and to compare it with the outcomes of patients receiving methotrexate (MTX) and cyclosporine-A (CsA) as a GVHD prophylaxis.

Patients and Methods: Seventy-five patients with advanced hematologic malignancies who underwent MRD allogeneic …

Preclinical Evaluation Of Immunomodulatory Effects Of Aurora Kinase Inhibition In Human Papillomavirus Positive Cancers, Pragya Sinha

Dissertations and Theses (Open Access)

Human papillomavirus (HPV) is the causative agent of cervical cancer and some cancers of the penis, vulva, vagina, anus, and oropharynx. Current therapies for these cancers include a combination of surgery, radiotherapy, and chemotherapy that often results in permanent, life altering adverse effects. Immunotherapy is partially effective, but with significant recurrence and lower long-term survival. Importantly, there are no few biomarker-selective targeted therapies for these cancers. To address this unmet need, our collaborators conducted a large-scale drug screen and identified Aurora Kinase (AK) inhibitors as a unique class of reagents to induce selective apoptosis in HPV+, but not HPV- human …

Regulation And Function Of Zeb1 Acetylation In Lung Adenocarcinoma Progression And Metastasis, Mabel Perez-Oquendo

Dissertations and Theses (Open Access)

Lung cancer metastasis is leading the causes of cancer-related mortality in the United States and worldwide. Epithelial-to-mesenchymal transition (EMT) is a model for metastasis that results in loss of specialized epithelial cell contacts and acquisition of mesenchymal invasive capacity. Zinc finger E-box-binding homeobox 1 (ZEB1) recognizes and binds to E-boxes of epithelial gene promoters to repress its transcription. ZEB1 has inconsistent molecular weights, which have been attributed to post-translational modifications (PTMs). In the presented dissertation, I specifically addressed the gap in the molecular mechanisms by which PTMs of ZEB1 regulate its ability to induce EMT and how its activity might …

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, …

Computational Modeling Of The Fanconi Anemia Gene Network And Its Connection To Cancer, Alyssa Warren-Belford

Biological Sciences Undergraduate Honors Theses

Fanconi anemia (FA) is a rare genetic condition in which the cell’s DNA repair machinery is dysregulated, significantly increasing the chances of tumorigenesis. Further research is being done in order to improve patient outcomes and incidences of cancer. Our group created a computational model of the FA DNA repair gene network, which removes interstrand crosslinks found in damaged DNA and repairs it so DNA synthesis can continue. Computer simulations show the number of DNA damage indicators decreased as the pathway continued. This was expected as the FA pathway repairs DNA damage. The goal of this project was to provide further …

Regulation Of De Novo And Maintenance Dna Methylation By Dnmt3a And Dnmt3b, Yang Zeng

Dissertations and Theses (Open Access)

DNA methylation (5-methylcytosine, 5mC) is essential for the regulation of gene expression and integrity of the mammalian genome. It occurs predominantly in the context of CpG dinucleotides to form a symmetrical pattern on both DNA strands, which allows DNA methylation patterns to be semi-conservatively maintained during DNA replication. There are two classes of DNA methyltransferases (DNMTs): DNMT3A and DNMT3B function primarily as de novo methyltransferases that establish DNA methylation patterns, whereas DNMT1 is the major enzyme responsible for maintaining DNA methylation patterns by converting hemi-methylated CpGs to fully methylated CpGs during DNA replication. Two accessory factors also play critical regulatory …

Investigating The Phenotypic Effects Of Ring1- And Yy1-Binding Protein (Rybp) In Glioblastoma Multiforme, Ronald W. Bucher

Graduate Theses

Glioblastoma multiforme (GBM) is an aggressive form of brain cancer that has horrendous survival outcomes with the use of current therapies. Further study into its molecular mechanisms will inform development of new, more effective treatments. The Polycomb protein RING1- and YY1- Binding Protein (RYBP) has emerged as an important gene in multiple cancers. In complex with other Polycomb proteins, RYBP acts to repress regions of chromatin, though it also performs other functions independent of these complexes. RYBP has a tumor suppressive role in various cancers, but may act as an oncogene in others, demonstrating its context-specific effects. The role of …

Investigating The Role Of Spatial Compartmentalization And Genomic Translocations In Metastatic Cancer: A Multi-Omic Analysis, Joshua Harris Garretson

Chancellor’s Honors Program Projects

No abstract provided.

Investigating Three Novel Porphyrins For The Possible Treatment For Lung Cancer Using Red And White Light, Emmy Hipps

Scholars Day Conference

Photodynamic therapy (PDT) is a treatment method for various illnesses including cancer that uses a special drug, called a photosensitizer (PS). When a patient is injected with a PS, over time the PS is absorbed by the cancerous tumor. Light is then applied to area for treatment. The light then causes the drug to be activated, and singlet oxygen is produced that kills the cells. The PS in partnership with light causes cancer cells to undergo apoptosis. This research focuses on testing three novel water-soluble porphyrins, ZnTPPEA, H2TPP – TRIS, and H2TPPADIPA, as potential photosensitizing agents. All three novel photosensitizing …

Apoptosis Induction In Jurkat T-Lymphocytes By Proton Pump Inhibitors (Ppis), Shreya Murali, Randall Reif

Student Research Submissions

Apoptosis, commonly known as programmed cell death, constantly occurs in humans. As a cancer cell increases in acidity, apoptosis is induced. In healthy cells, proton pump proteins allow for H⁺ ions to permeate cellular membranes, regulating pH. However, proton pump inhibitors (PPIs), such as omeprazole, prevent proton movement. In previous studies, omeprazole induced cell death in Jurkat T lymphocytes; however, there was no confirmation of whether the cells died through apoptosis, or through necrosis, where the cell bursts. By using Annexin-V staining, the effects of omeprazole, dexlansoprazole, and esomeprazole on apoptosis induction can be measured. Cell death was observed …

Effect Of Tetracycline Derivatives On Metastasis In A Murine Mammary Tumor Model, Anna King, John Pryor, Serratt Nong

Liberty University Research Week

Undergraduate

Basic

Transcriptional Silencing Of Cdk18 And Its Role In Lung Carcinogenesis Of Brg1-Mutant Lung Cancers, Loryn M. Phillips

Biology ETDs

BRG1 is mutated in 10% of lung cancers, making this mutation clinically relevant. The downstream effects of BRG1 included significantly affecting the cell cycle control and chromosomal replication pathway. CDK18, a cyclin-dependent kinase, was determined to be the gene with significantly decreased expression (p

Utilizing Mass Spectrometry Imaging To Correlate N-Glycosylation Of Hepatocellular Carcinoma With Tumor Subtypes For Biomarker Discovery, Andrew Delacourt

MUSC Theses and Dissertations

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths globally and is a growing clinical problem with poor survival outcomes beyond early-stage disease. Surveillance for HCC has primarily relied on ultrasound and serum α-fetoprotein (AFP), but combined they only have a sensitivity of 63% for early-stage HCC tumors, suggesting a need for improved diagnostic strategies. Alterations to N-glycan expression are relevant to the progression of cancer, and there a multitude of N-glycan-based cancer biomarkers that have been identified with sensitivity for various cancer types including HCC. Spatial HCC tissue profiling of N-linked glycosylation by matrix-assisted laser desorption ionization imaging …

Jak2/Stat5 Pathway Mutation Frequencies In South African Bcr/Abl Negative Mpn Patients, Shires K, Rust A, Harryparsad R, Coburn J, Gopie R

Hematology/Oncology and Stem Cell Therapy

Background: Mutations in JAK2/STAT5 proliferation pathway genes are key in the diagnosis of myeloproliferative neoplasms (MPNBCR/ABLneg), with JAK2V617F being found in 50-97% of MPNBCR/ABLneg subtypes. Low JAK2V617F positivity at our facility suggested that our South African MPNBCR/ABLneg population may have a different mutational landscape. Objectives: We aimed to determine the JAK2/STAT5 mutation frequencies associated with our local MPNBCR/ABLneg population, thus determining the relevance of these molecular tests in this group. We also investigated the haematopathological relevance of each test request, to assess testing practises. Method: This study involved the retrospective audit of 886 patients for whom JAK2V617F mutation testing had …