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 …

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 …

Design, Synthesis, And Antiproliferative Activity Of Benzopyran-4-One-Isoxazole Hybrid Compounds, Shilpi Gupta, Shang Eun Park, Saghar Mozaffari, Bishoy El-Aarag, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5a–d displayed significant antiproliferative activities against all the cancer cell lines tested, and IC₅₀ values were in the range of 5.2–22.2 μM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC₅₀ values of 5a–d …

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% …

Parkin Ubiquitination Of Kindlin-2 Enables Mitochondria-Associated Metastasis Suppression, Minjeong Yeon, Irene Bertolini, Ekta Agarwal, Jagadish C Ghosh, Hsin-Yao Tang, David W. Speicher, Frederick Keeney, Khalid Sossey-Alaoui, Elzbieta Pluskota, Katarzyna Bialkowska, Edward F. Plow, Lucia R. Languino, Emmanuel Skordalakes, M Cecilia Caino, Dario C. Altieri

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Mitochondria are signaling organelles implicated in cancer, but the mechanisms are elusive. Here, we show that Parkin, an E3 ubiquitination (Ub) ligase altered in Parkinson's disease, forms a complex with the regulator of cell motility, Kindlin-2 (K2), at mitochondria of tumor cells. In turn, Parkin ubiquitinates Lys581 and Lys582 using Lys48 linkages, resulting in proteasomal degradation of K2 and shortened half-life from ∼5 h to ∼1.5 h. Loss of K2 inhibits focal adhesion turnover and β1 integrin activation, impairs membrane lamellipodia size and frequency, and inhibits mitochondrial dynamics, altogether suppressing tumor cell-extracellular matrix interactions, migration, and invasion. Conversely, Parkin does …

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 …

A Dna-Peptide Crosslink (Dpc) Increases Mutagenicity In Sos-Induced Escherichia Coli, Alessandra Bassani

Honors Scholar Theses

Bacteria, such as Escherichia coli, have an inducible system in response to DNA damage termed the SOS response. This system is activated when the replicative DNA polymerase (Pol) III encounters a lesion, uncouples from DNA helicase, and single-stranded DNA (ssDNA) accumulates at the replication fork. In this study, we investigated DNA-peptide crosslink (DpC), a common lesion that results from cross-linking of proteins or peptides, UV irradiation, and alkylating agents. To increase survival following formation of a lesion, the SOS response can utilize homologous recombination, translesion synthesis (TLS), or excision repair. With TLS, the levels of DNA Pol II, IV, …

Oncolytic Virus Immunotherapy: Development And Potential For Cancer Treatment, Olivia Guinness

Honors Scholar Theses

The American Cancer Society estimates that in 2023, 1,958,310 new cancer cases and 609,820 cancer deaths will occur in the United States [16]. A promising therapeutic option that has been supported by recent clinical trials is the use of oncolytic viruses to treat malignant tumors. The mechanism of action of existing treatments, such as chemotherapy, radiotherapy, and surgery, differs from that of oncolytic virus therapy because oncolytic viruses are able to affect cancer cells with specificity, minimizing side effects. When infecting a normal, non-cancerous cell, oncolytic viruses do not replicate, leaving healthy cells unaffected. In tumor cells, oncolytic viruses will …

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 …

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 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 …

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, …

P53 Dimers Elicit Unique Tumor Suppressive Activities Through An Altered Metabolic Program, Jovanka Gencel-Augusto

Dissertations and Theses (Open Access)

p53 is the most frequently mutated tumor suppressor in human cancer. As a tetrameric transcription factor, mutation of the p53 Tetramerization Domain (TD) is a mechanism by which cancers abrogate wild-type (WT) p53 function. p53 TD mutations result in a protein that preferentially forms monomers or dimers. These are also normal p53 states under basal cellular conditions. Although it is accepted that tetrameric p53 is required for full tumor suppressive activities, the physiological relevance of monomeric and dimeric states of p53 is not well understood. We have established in vivo models for monomeric and dimeric p53 which model Li-Fraumeni Syndrome …

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 …