Medicine and Health Sciences Commons^™

Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi

USF Tampa Graduate Theses and Dissertations

NRF2 is a redox-responsive transcription factor the directs the antioxidant program and several critical metabolic processes. Mutations in NRF2 or its negative regulator KEAP1 occur in up to one third of non-small cell lung cancers (NSCLCs) and are often associated with resistance to therapy and poor outcomes. In the present studies, murine alleles of the Keap1 and Nrf2 mutations found in human NSCLC were developed and I comprehensively investigated their impact on tumor initiation and progression. I observed that chronic Nrf2 stabilization by Keap1 loss-of-function or Nrf2 activating mutation was not sufficient to cause lung tumor initiation, even when p53 …

Interferon-Β Activity Is Affected By S100b Protein, Alexey S. Kazakov, Alexander D. Sofin, Nadezhda V. Avkhacheva, Eugenia I. Deryusheva, Victoria A. Rastrygina, Maria E. Permyakova, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov

Molecular Medicine Faculty Publications

Interferon-β (IFN-β) is a pleiotropic cytokine secreted in response to various pathological conditions and is clinically used for therapy of multiple sclerosis. Its application for treatment of cancer, infections and pulmonary diseases is limited by incomplete understanding of regulatory mechanisms of its functioning. Recently, we reported that IFN-β activity is affected by interactions with S100A1, S100A4, S100A6, and S100P proteins, which are members of the S100 protein family of multifunctional Ca2+-binding proteins possessing cytokine-like activities (Int J Mol Sci. 2020;21(24):9473). Here we show that IFN-β interacts with one more representative of the S100 protein family, the S100B protein, involved in …

Evolution Of Targeted Therapy Resistance In Eml4-Alk Positive Non-Small Cell Lung Cancer, Robert Vander Velde

USF Tampa Graduate Theses and Dissertations

Targeted therapies have emerged as potent treatments that lead to the remission of many tumors. However, they rarely cure cancers in advanced, metastatic settings. This is due to the evolution of resistance, which in turn can be ascribed to the survival of small subpopulations of tolerant and/or resistant cells. Here we investigated the evolution of resistance to EML4-ALK inhibitors in non-small cell lung cancer (NSCLC) and demonstrated that resistance evolves gradually, from unique pre-treatment sub-populations, as multiple resistance mechanisms accumulate in a Darwinian fashion. Despite accumulating multiple changes, cells evolved, in parallel, toward similar inhibitor specific phenotypes. Evolving cells have …

Potential Molecular Mechanisms Of Rare Anti-Tumor Immune Response By Sars-Cov-2 In Isolated Cases Of Lymphomas, Debmalya Barh, Sandeep Tiwary, Lucas Gabriel Rodrigues Gomes, Marianna E. Weener, Khalid J. Alzahrani, Khalaf F. Alsharif, Alaa A. A. Aljabali, Murtaza M. Tambuwala, Kenneth Lundstrom, Sk. Sarif Hassan, Ángel Serrano-Aroca, Kazuo Takayama, Preetam Ghosh, Elrashdy M. Redwan, Bruno Silva Andrade, Siomar De Castro Soares, Vasco Azevedo, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Recently, two cases of complete remission of classical Hodgkin lymphoma (cHL) and follicular lymphoma (FL) after SARS-CoV-2 infection were reported. However, the precise molecular mechanism of this rare event is yet to be understood. Here, we hypothesize a potential anti-tumor immune response of SARS-CoV-2 and based on a computational approach show that: (i) SARS-CoV-2 Spike-RBD may bind to the extracellular domains of CD15, CD27, CD45, and CD152 receptors of cHL or FL and may directly inhibit cell proliferation. (ii) Alternately, upon internalization after binding to these CD molecules, the SARS-CoV-2 membrane (M) protein and ORF3a may bind to gamma-tubulin complex …

The Participation Of The Intrinsically Disordered Regions Of The Bhlh-Pas Transcription Factors In Disease Development, Marta Kolonko-Adamska, Vladimir N. Uversky, Beata Greb-Markiewicz

Molecular Medicine Faculty Publications

The basic helix–loop–helix/Per-ARNT-SIM (bHLH-PAS) proteins are a family of transcription factors regulating expression of a wide range of genes involved in different functions, ranging from differentiation and development control by oxygen and toxins sensing to circadian clock setting. In addition to the well-preserved DNA-binding bHLH and PAS domains, bHLH-PAS proteins contain long intrinsically disordered C-terminal regions, responsible for regulation of their activity. Our aim was to analyze the potential connection between disordered regions of the bHLH-PAS transcription factors, post-transcriptional modifications and liquid-liquid phase separation, in the context of disease-associated missense mutations. Highly flexible disordered regions, enriched in short motives which …

“They Will Think We Are The Cancer Family”: Studying Patterns Of Cancer Disclosure And Communication Among Indian Immigrants In The United States, Kanan Mehta

USF Tampa Graduate Theses and Dissertations

Studies of Indian immigrants in Western countries show that the rates of cancer increase significantly within a generation in the host country. The negative social perceptions associated with health outcomes of cancer often perpetuate limited disclosure regarding the diagnosis of cancer among patients and families. This can result in disrupted communication in clinical settings, while causing increased stress among patients and caregivers. These findings demonstrate the need for studying lived experiences of cancer-related illness and its impacts on social relationships in the domestic and public sphere.

This study explored cancer disclosure and communication among Indian immigrants in the United States …

Interferon Beta Activity Is Modulated Via Binding Of Specific S100 Proteins, Alexei S. Kazakov, Alexander D. Sofin, Nadezhda V. Avkhacheva, Alexander I. Denesyuk, Eugenia I. Deryusheva, Victoria A. Rastrygina, Andrey S. Sokolov, Maria E. Permyakova, Ekaterina A. Litus, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov

Molecular Medicine Faculty Publications

Interferon-β (IFN-β) is a pleiotropic cytokine used for therapy of multiple sclerosis, which is also effective in suppression of viral and bacterial infections and cancer. Recently, we reported a highly specific interaction between IFN-β and S100P lowering IFN-β cytotoxicity to cancer cells (Int J Biol Macromol. 2020; 143: 633–639). S100P is a member of large family of multifunctional Ca2+-binding proteins with cytokine-like activities. To probe selectivity of IFN-β—S100 interaction with respect to S100 proteins, we used surface plasmon resonance spectroscopy, chemical crosslinking, and crystal violet assay. Among the thirteen S100 proteins studied S100A1, S100A4, and S100A6 proteins exhibit strictly Ca2+-dependent …

Unstructured Biology Of Proteins From Ubiquitin-Proteasome System: Roles In Cancer And Neurodegenerative Diseases, Kundlik Gadhave, Prateek Kumar, Shivani K. Kapuganti, Vladimir N. Uversky, Rajanish Giri

Molecular Medicine Faculty Publications

The 26S proteasome is a large (~2.5 MDa) protein complex consisting of at least 33 different subunits and many other components, which form the ubiquitin proteasomal system (UPS), an ATP-dependent protein degradation system in the cell. UPS serves as an essential component of the cellular protein surveillance machinery, and its dysfunction leads to cancer, neurodegenerative and immunological disorders. Importantly, the functions and regulations of proteins are governed by the combination of ordered regions, intrinsically disordered protein regions (IDPRs) and molecular recognition features (MoRFs). The structure–function relationships of UPS components have not been identified completely; therefore, in this study, we have …

The Moderating Effect Of Religion On Death Distress And Quality Of Life Between Christian Cancer Patients In The United States With Muslim Cancer Patients In Saudi Arabia, Doaa Almostadi

USF Tampa Graduate Theses and Dissertations

Cancer is an illness that knows no international boundaries. There are more than eight million global cancer deaths each year. A life-threatening diagnosis generates significant emotional problems for many patients across cultures. Death distress—consisting of death depression, death anxiety and death obsession—often results in poorer treatment adherence and lower overall health and quality of life. The purpose of this study was to determine whether religiosity has a moderating effect on the relationship between death distress and quality of life among patients facing a life-threatening cancer diagnosis.

The study sample consisted of 118 cancer patients: 82 cancer patients from a National …

Cell Cycle Arrest By Tgfß1 Is Dependent On The Inhibition Of Cmg Helicase Assembly And Activation, Brook Samuel Nepon-Sixt

USF Tampa Graduate Theses and Dissertations

Tumorigenesis is a multifaceted set of events consisting of the deregulation of several cell-autonomous and tissue microenvironmental processes that ultimately leads to the acquisition of malignant disease. Transforming growth factor beta (TGFß) and its family members are regulatory cytokines that function to ensure proper organismal development and the maintenance of homeostasis by controlling cellular differentiation, proliferation, adhesion, and survival, as well as by modulating components of the cellular microenvironment and immune system. The pleiotropic control by TGFß of these cell intrinsic and extrinsic factors is intimately linked to the prevention of tumor formation, the specifics of which are dependent on …

Factors Associated With Fear Of Breast Cancer Recurrence Among Survivors, Jean Marie Lucas

USF Tampa Graduate Theses and Dissertations

The purpose of this cross-sectional, secondary data analysis was to explore, non-modifiable (stable) trait factors and modifiable (transient) state factors associated with fear of recurrence (FOR) in breast cancer survivors. Antecedent trait factors included demographic, clinical, social/behavioral factors, postulated mediator state factors included pain, fatigue, sleep disturbances, depression, state anxiety and perceived stress, and FOR was the outcome variable. The study used baseline data from an R-21 NCI funded (grant #R21CA109168) randomized control trial that examined the effects of mindfulness based stress reduction in early stage breast cancer recovery. Instruments from this study for antecedent variables (trait factors) included a …

Distribution And Cluster Analysis Of Predicted Intrinsically Disordered Protein Pfam Domains, Robert W. Williams, Bin Xue, Vladimir N. Uversky, A. Keith Dunker

Molecular Medicine Faculty Publications

The Pfam database groups regions of proteins by how well hidden Markov models (HMMs) can be trained to recognize similarities among them. Conservation pressure is probably in play here. The Pfam seed training set includes sequence and structure information, being drawn largely from the PDB. A long standing hypothesis among intrinsically disordered protein (IDP) investigators has held that conservation pressures are also at play in the evolution of different kinds of intrinsic disorder, but we find that predicted intrinsic disorder (PID) is not always conserved across Pfam domains. Here we analyze distributions and clusters of PID regions in 193024 members …

Framing Colombian Women's Beliefs, Values And Attitude Towards Sex And Sexual High-Risk Behaviors, Rosa Ore

USF Tampa Graduate Theses and Dissertations

Hispanic immigrants constitute the largest and fastest growing groups of minorities in the United States. According to the 2010 Census, there are 50.5 million Hispanics in the United States, making up 16.3% of the total population (Passel, Cohn & Lopez, 2011). Furthermore, the state of Florida is home to 4,223,806 Hispanics (U.S. Census Bureau, 2010). Because the Hispanic population continues to grow, it is important to study their sexual health behaviors because diseases linked to risky sexual behaviors account for approximately 20,000 U.S. deaths each year, and are linked to a number of adverse reproductive outcomes (Abraido-Lanza, Chao, & Florez, …

The Relationship Between Death Depression And Death Anxiety Among Cancer Patients In Saudi Arabia, Doaa A. Almostadi

USF Tampa Graduate Theses and Dissertations

Abstract

Cancer is one of the main public health problems in the world. People diagnosed with cancer may become depressed and fearful of dying. This causes them to question treatments and sometimes avoid treatment altogether. Cancer may change the person's life and the lives of others around them. The current study focused on the psychosocial impact of impending death for cancer patients in Saudi Arabia. Currently, the relationship between the death anxiety and death depression in persons with cancer in Saudi Arabia is not yet clear. Added to that, little research has been conducted with Muslim cancer patients and their …

Matrix Metalloproteinase Genes Are Transcriptionally Regulated By E2f Transcription Factors: A Link Between Cell Cycle Control And Metastatic Progression, Jacqueline Lea Johnson

USF Tampa Graduate Theses and Dissertations

The RbµE2F transcriptional regulatory pathway plays a critical role in the cell cycle. Rb is inactivated through multiple waves of phosphorylation, mediated mainly by cyclin D and cyclin E associated kinases. Once Rb is inactivated, cells can enter Sµphase. Collectively, three Rb family members and ten E2F proteins coordinate every additional stage of the cell cycle, from quiescence to mitosis. However the RbµE2F pathway is frequently altered in cancer. Aside from cell proliferation, the RbµE2F pathway regulates other essential cellular processes including apoptosis, cell differentiation, angiogenesis and DNA damage repair pathways, but its role in invasion and cancer progression is …