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Targeting Of The Hedgehog Signaling Pathway In Cancer Treatment, Andrew J. Hawes 2022 University of Louisville

Targeting Of The Hedgehog Signaling Pathway In Cancer Treatment, Andrew J. Hawes

The Cardinal Edge

The Hedgehog (Hh) signaling pathway is a developmental pathway that is highly conserved evolutionarily. While typically only displaying high activity during embryogenesis, overactivation of the Hh pathway in adults has been linked to multiple forms of cancer including acute myeloid leukemia, myelofibrosis, basal-cell carcinoma, pancreatic ductal adrenal carcinoma, and triple negative breast cancer. The prevalence of Hh activation in many different cancers has made it a prime target for inhibition of these cancers through novel therapies. This literature review sought to assess the current state of cancer treatment through inhibition of Hh signaling. Most current clinical trials involving the pathway ...


Determining The Roles Of The Oligomerization And C-Terminal Domains In Mutant P53 Gain-Of-Function Activities, George K. Annor 2022 The Graduate Center, City University of New York

Determining The Roles Of The Oligomerization And C-Terminal Domains In Mutant P53 Gain-Of-Function Activities, George K. Annor

Dissertations, Theses, and Capstone Projects

The tumor suppressor p53 (TP53) gene is often mutated in cancer, with missense mutations found in the central DNA binding domain, and less often in the oligomerization domain (OD) and C-terminal domain (CTD). The OD and CTD have been found to be critical for the tumor suppressor functionality of wild-type p53 (wtp53). Specific missense mutations in the DNA binding domain have been found to confer new gain-of-function (GOF) activities. Mutations that destabilize tetramer formation, or deletion of key lysine residues within the CTD, downregulate the ability of wtp53 to transactivate (increase the rate of transcription of) its target genes. We ...


Characterization Of Exosomes And Their Role In Cellular Migration In Chemosensitive And Chemoresistant Ovarian Cancer Cells, Courtney McEneaney 2022 Bridgewater State University

Characterization Of Exosomes And Their Role In Cellular Migration In Chemosensitive And Chemoresistant Ovarian Cancer Cells, Courtney Mceneaney

Honors Program Theses and Projects

Chemotherapy-resistant cells that remain after primary cancer treatment lead to recurrence and metastasis, resulting in a poor prognosis for patients. Chemoresistant cells were created by our collaborators using the human ovarian cancer cell line, OVCAR8, by selection of cells that survived serial culture with cisplatin, a platinum-based chemotherapeutic. The cisplatin-resistant cells (OVCAR8R) demonstrate a morphology unique from the original cisplatin-sensitive cells (OVCAR8) which could correlate with their difference in aggressiveness. My research goal is to isolate and characterize exosomes from the OVCAR8 and OVCAR8Rlines. Exosomes are small vesicles secreted from cells and contribute to the tumor microenvironment(TME). It has ...


The Role Of Increased Matrix Metalloproteinase (Mmp14) Expression On Apoptosis Sensitivity In Human Breast Cancer Cells, Roukayah Rifai 2022 Western University

The Role Of Increased Matrix Metalloproteinase (Mmp14) Expression On Apoptosis Sensitivity In Human Breast Cancer Cells, Roukayah Rifai

Undergraduate Student Research Internships Conference

A member of the matrix metalloproteinase family (MMP14) plays a crucial role in extracellular matrix (ECM) remodeling, as it possesses characteristics that aid in cell proliferation and differentiation. MMP14 domains can bind to FIH-1, which is a protein that can prevent apoptosis in cells when attached to BAX in the mitochondria. This study will investigate the varying expressions of MMP14 on FIH-1 and BAX, and their effects on apoptotic sensitivity. Three cell lines with varying levels of MMP14 expression will be used: C3 (~11 fold), ΔCD (~100 fold), and C2 (~500 fold). With the overexpression of MM14 on the cell ...


Non-Photic Mechanisms Of Entrainment In Bmal1 Deficient Conditions, Jamie Tran 2022 The Texas Medical Center Library

Non-Photic Mechanisms Of Entrainment In Bmal1 Deficient Conditions, Jamie Tran

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Maintaining our internal circadian (i.e. 24 -hour) clock is imperative to our daily biological and mental well-being. Large epidemiological studies have shown that disruptions of our circadian rhythms can lead to poor mental health, metabolic diseases, and various types of cancer. Various external cues that have become a part of the modern times such as electricity, shift -work, rapid travel across various time zones, easier access to nutritionally unbalanced food items, and various rigid social demands have deleterious effects on our internal clock, and generally reduce robustness of the circadian clock. The two following projects aim to examine two ...


The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia 2022 The Texas Medical Center Library

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME ...


Gaps In Patient Education On Safe Handling And Disposal Of Oral Chemotherapy Drugs: A Pilot Prospective Cohort Survey Study, Sun Yang, Priya Patel, Alexandra Corcoran, Eric Dobberpuhl, Samantha Isidro, Dustin Le, Analise Klassen, Jay Rho, David Tran, Richard Beuttler, Neda Noori Nassr, Katherine Gruenberg, Siu-Fun Wong 2022 Chapman University

Gaps In Patient Education On Safe Handling And Disposal Of Oral Chemotherapy Drugs: A Pilot Prospective Cohort Survey Study, Sun Yang, Priya Patel, Alexandra Corcoran, Eric Dobberpuhl, Samantha Isidro, Dustin Le, Analise Klassen, Jay Rho, David Tran, Richard Beuttler, Neda Noori Nassr, Katherine Gruenberg, Siu-Fun Wong

Pharmacy Faculty Articles and Research

Background

Oral anticancer chemotherapy (OC) has been misperceived as being safer than intravenous chemotherapy, leading to its increased risk of improper handling and disposal. This survey study assessed the knowledge, practices and attitudes of pharmacists and patients regarding OC handling and disposal, gaps in knowledge and barriers to patient education. Methods

Surveys were developed based on literature review and pilot study validation results. Patients completed a 33-item paper or electronic survey whereas pharmacists completed a 38-item electronic survey. Descriptive statistics and Fisher’s exact test computed using the R Project were used for analyses. Results

Pharmacist group (16/25, 62 ...


The Roles Of Epithelial–Mesenchymal Plasticity In Tumor Heterogeneity, Metastasis, And Patient Survival In Breast Cancer, Meredith Septer Brown 2022 Dartmouth College

The Roles Of Epithelial–Mesenchymal Plasticity In Tumor Heterogeneity, Metastasis, And Patient Survival In Breast Cancer, Meredith Septer Brown

Dartmouth College Ph.D Dissertations

The Epithelial-to-Mesenchymal transition, a critical cellular process in development, is frequently co-opted by solid tumors to promote invasion and metastasis. In particular, the hybrid or intermediate EMT state, possessing both epithelial and mesenchymal characteristics, is associated with increased cancer stemness and plasticity. Similarly, intra-tumoral heterogeneity in solid tumors, in particular breast cancer, is associated with poor prognosis, tumor growth, proliferation, drug resistance, and metastasis. We sought to understand the link between the generation of intra-tumoral heterogeneity and the intermediate EMT state and their impact on tumor progression and patient prognosis. As part of my thesis work, I developed a model ...


Combined Curcumin And Luteolin Synergistically Inhibit Colon Cancer Associated With Notch1 And Tgf-Β Signaling Pathways In Cultured Cells And Xenograft Mice, Rukayat Aromokeye, Hongwei Si 2022 Tennessee State University

Combined Curcumin And Luteolin Synergistically Inhibit Colon Cancer Associated With Notch1 And Tgf-Β Signaling Pathways In Cultured Cells And Xenograft Mice, Rukayat Aromokeye, Hongwei Si

Human Sciences Faculty Research

This study aimed to select a combination of curcumin and luteolin, two phytochemicals from food, at lower concentrations with a higher inhibitory effect on colon cancer growth and investigate possible molecular mechanisms of this anti-colon cancer effect. By pairwise combination screening, we identified that the combination of curcumin (CUR) at 15 μM and luteolin (LUT) at 30 μM (C15L30) synergistically suppressed the proliferation of human colon cancer CL-188 cells, but the individual chemicals had a little inhibitory effect at the selected concentrations. This result was also confirmed in other colon cancer DLD-1cells, suggesting that this synergistic inhibitory effect of C15L30 ...


Tracking And Modulating Circadian Rhythms In Cell Culture Models, Sujeewa Sampath Lellupitiyage Don 2022 University of Massachusetts Amherst

Tracking And Modulating Circadian Rhythms In Cell Culture Models, Sujeewa Sampath Lellupitiyage Don

Doctoral Dissertations

Circadian rhythms are 24–hour activity cycles that exist for all organisms, from yeast and bacteria to mammals. Epidemiological data has shown that disruptions to circadian rhythms are associated with various diseases, including cancers. Circadian rhythms are regulated at the cellular level by a "molecular clock,” whose oscillations in protein transcription and translation control a range of downstream pathways. However, the connections between altered rhythms and diseases at the molecular level is unclear. Therefore, in this project, I tracked circadian rhythms in a high-resolution manner and thoroughly analyzed them to more completely reflect circadian behaviors and clock functioning at the ...


Complex Role Of Microbiome In Pancreatic Tumorigenesis: Potential Therapeutic Implications, Suneetha Amara, Li V. Yang, Venkataswarup Tiriveedhi, Mahvish Muzaffar 2022 East Carolina University

Complex Role Of Microbiome In Pancreatic Tumorigenesis: Potential Therapeutic Implications, Suneetha Amara, Li V. Yang, Venkataswarup Tiriveedhi, Mahvish Muzaffar

Biology Faculty Research

Pancreatic cancer (PC) is the fourth leading cause of cancer-related mortality with limited diagnostic and therapeutic options. Although immunotherapy has shown promise in the treatment of several cancers, its role in pancreatic cancer is rather limited. Several studies have focused on determining the role of the tumor microenvironment with cancer-cell-intrinsic events and tumor-infiltrating immune cellular properties. However, in the past decade, there has been emerging research aimed at delineating the role of the host microbiome, including the metabolites from microbes and host responses, on pancreatic tumorigenesis. Importantly, there is emerging evidence suggesting the beneficial role of a gut microbiome transplant ...


Spectrum Of Myelodysplastic Syndrome In Patients Evaluated For Cytopenia(S). A Report From A Reference Centre In Saudi Arabia, Nour AlMozain, Ayman Mashi, Qasem Alneami, Amal Al-Omran, Nasir Bakshi, Tarek Owaidah, Salem Khalil, Haitham Khogeer, Shahrukh Hashmi, Suleimman Al-Sweedan, Thomas Morris, Randa AlNounou 2022 Department of the Blood Bank, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia

Spectrum Of Myelodysplastic Syndrome In Patients Evaluated For Cytopenia(S). A Report From A Reference Centre In Saudi Arabia, Nour Almozain, Ayman Mashi, Qasem Alneami, Amal Al-Omran, Nasir Bakshi, Tarek Owaidah, Salem Khalil, Haitham Khogeer, Shahrukh Hashmi, Suleimman Al-Sweedan, Thomas Morris, Randa Alnounou

Hematology/Oncology and Stem Cell Therapy

Background/Objective: Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells, characterized by ineffective hematopoiesis, peripheral cytopenias along with hypercellularity of the bone marrow, and marked dysplastic features. Establishing MDS diagnosis is difficult due to nonspecific clinical presentation and imprecise morphological criteria. In anticipation to improve the diagnostic approach in this field, we aimed to characterize the clinical and morphological features of patients presented with cytopenias with a special focus on MDS. Methods: We comprehensively reviewed all medical record of patients who were referred to the hematology laboratory at KFSH-RC, Riyadh, Saudi Arabia, between January 2009 and March ...


The Risk And Prognosis Of Covid-19 Infection In Cancer Patients: A Systematic Review And Meta-Analysis, Ghada M. ElGohary, Shahrukh Hashmi, Jan Styczynski, Mohamed A. Kharfan-Dabaja, Rehab M. Alblooshi, Rafael de la Camara, Sherif Mohmed, Alfadel Alshaibani, Simone Cesaro, Nashwa Abd El-Aziz, Reem Almaghrabi, Usama Gergis, Navneet S. Majhail, Roy F. Chemaly, Mahmoud Aljurf, Riad El Fakih 2022 Department of Medicine, Division of Oncology/Hematology, College of Medicine, King Saud University Medical City, Riyadh, Saudi Arabia

The Risk And Prognosis Of Covid-19 Infection In Cancer Patients: A Systematic Review And Meta-Analysis, Ghada M. Elgohary, Shahrukh Hashmi, Jan Styczynski, Mohamed A. Kharfan-Dabaja, Rehab M. Alblooshi, Rafael De La Camara, Sherif Mohmed, Alfadel Alshaibani, Simone Cesaro, Nashwa Abd El-Aziz, Reem Almaghrabi, Usama Gergis, Navneet S. Majhail, Roy F. Chemaly, Mahmoud Aljurf, Riad El Fakih

Hematology/Oncology and Stem Cell Therapy

Numerous studies have been published regarding outcomes of cancer patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causing the coronavirus disease 2019 (COVID-19) infection. However, most of these are single-center studies with a limited number of patients. To better assess the outcomes of this new infection in this subgroup of susceptible patients, we performed a systematic review and meta-analysis to evaluate the impact of COVID-19 infection on cancer patients. We performed a literature search using PubMed, Web of Science, and Scopus for studies that reported the risk of infection and complications of COVID-19 in cancer patients ...


The Phenomenon Of Multidrug Resistance In Glioblastomas, Alexandr N. Chernov, Diana A. Alaverdian, Elvira S. Galimova, Alessandra Renieri, Elisa Frullanti, Ilaria Meloni, Olga V. Shamova 2022 Institute of Experimental Medicine, Russian Academy of Medical Sciences, Saint-Petersburg, Russia

The Phenomenon Of Multidrug Resistance In Glioblastomas, Alexandr N. Chernov, Diana A. Alaverdian, Elvira S. Galimova, Alessandra Renieri, Elisa Frullanti, Ilaria Meloni, Olga V. Shamova

Hematology/Oncology and Stem Cell Therapy

The most common and aggressive brain tumor in the adult population is glioblastoma (GBM). The lifespan of patients does not exceed 22 months. One of the reasons for the low effectiveness of GBM treatment is its radioresistance and chemoresistance. In the current review, we discuss the phenomenon of multidrug resistance of GBM in the context of the expression of ABC family transporter proteins and the mechanisms of proliferation, angiogenesis, and recurrence. We focused on the search of molecular targets among growth factors, receptors, signal transduction proteins, microRNAs, transcription factors, proto-oncogenes, tumor suppressor genes, and their single-nucleotide polymorphisms.


Hepatitis-Associated Aplastic Anemia, Alfadel Alshaibani, Carlo Dufour, Antonio Risitano, Regis de Latour, Mahmoud Aljurf 2022 King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Hepatitis-Associated Aplastic Anemia, Alfadel Alshaibani, Carlo Dufour, Antonio Risitano, Regis De Latour, Mahmoud Aljurf

Hematology/Oncology and Stem Cell Therapy

Hepatitis-associated aplastic anemia (HAAA) is a rare illness, characterized by onset of pancytopenia with a hypoplastic bone marrow that traditionally occurs within 6 months of an increase in serum aminotransferases. HAAA is observed in 1% to 5% of all newly diagnosed cases of acquired aplastic anemia. Several hepatitis viruses have been linked to the disease, but in many cases no specific virus is detected. The exact pathophysiology is unknown; however, immune destruction of hematopoietic stem cells is believed to be the underlying mechanism. HAAA is a potentially lethal disease if left untreated. Management includes immunosuppression with antithymocyte globulin and cyclosporine ...


Mutation Profile In Bcr-Abl1-Negative Myeloproliferative Neoplasms: A Single-Center Experience From India, Madhavi Maddali, Uday Prakash Kulkarni, Niveditha Ravindra, Arun Kumar Arunachalam, Arvind Venkatraman, Sharon Lionel, Marie Therese Manipadam, Anup J. Devasia, Anu Korula, N.A. Fouzia, Aby Abraham, Alok Srivastava, Biju George, Poonkuzhali Balasubramanian, Vikram Mathews 2022 Department of Haematology, Christian Medical College, Vellore, India

Mutation Profile In Bcr-Abl1-Negative Myeloproliferative Neoplasms: A Single-Center Experience From India, Madhavi Maddali, Uday Prakash Kulkarni, Niveditha Ravindra, Arun Kumar Arunachalam, Arvind Venkatraman, Sharon Lionel, Marie Therese Manipadam, Anup J. Devasia, Anu Korula, N.A. Fouzia, Aby Abraham, Alok Srivastava, Biju George, Poonkuzhali Balasubramanian, Vikram Mathews

Hematology/Oncology and Stem Cell Therapy

Objective/Background: Recurrent somatic mutations in the JAK2, calreticulin (CALR), and the MPL genes are described as drivers of BCR-ABL1-negative myeloproliferative neoplasms (MPN) that includes polycythemia vera (PV), essential thrombocytosis (ET), primary myelofibrosis (PMF), and MPN unclassified (MPN-U). Methods: We describe the mutation profile and clinical features of MPN cases diagnosed at a tertiary care center. JAK2V617F and MPL (S505/W515) mutations were screened by allele-specific polymerase chain reaction, while CALR exon 9 and JAK2 exon 12 mutations were screened by fragment analysis/Sanger sequencing. Among the 1,570 patients tested for these mutations during the study period, 407 were ...


The Hispanic Paradox In Non-Small Cell Lung Cancer, Rohit Kumar, Franklin Castillero, Shruti Bhandari, Sindhu Malapati, Goetz Kloecker 2022 Division of Medical Oncology and Hematology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

The Hispanic Paradox In Non-Small Cell Lung Cancer, Rohit Kumar, Franklin Castillero, Shruti Bhandari, Sindhu Malapati, Goetz Kloecker

Hematology/Oncology and Stem Cell Therapy

Objective/Background: According to the U.S. Census Bureau, 18% of the total population in the United States identified themselves as Hispanic in 2016 making it the largest minority group. This study aimed to evaluate the effect of Hispanic ethnicity on the overall survival of patients with non-small cell lung cancer (NSCLC) using a large national cancer database. Methods: We used the National Cancer Database to identify patients diagnosed with NSCLC between 2010 and 2015. The two comparative groups for this study were non-Hispanic Whites (NHWs) and Hispanics. The primary outcome was overall survival. Results: Of the 555,475 patients ...


Does Race Play A Role In Complications And Outcomes Of Philadelphia Chromosome-Negative Myeloproliferative Neoplasms?, Andrew M. Peseski, Antoine N. Saliba, Sandra K. Althouse, Hamid Sayar 2022 Indiana University School of Medicine, Department of Medicine, Indianapolis, IN, USA

Does Race Play A Role In Complications And Outcomes Of Philadelphia Chromosome-Negative Myeloproliferative Neoplasms?, Andrew M. Peseski, Antoine N. Saliba, Sandra K. Althouse, Hamid Sayar

Hematology/Oncology and Stem Cell Therapy

Background: Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are a group of hematologic malignancies with known vascular complications. The role race and ethnicity play in these complications is less defined. We aimed to further evaluate the role of race in patients without a history of previous thrombotic or hemorrhagic events. Methods: In this retrospective study, 300 adult patients with MPN were included; 270 (90.0%) were White and 30 (10.0%) were non-White. The non-White group primarily consisted of African American or Black (26 patients), followed by others. Median age at diagnosis was 58 years for White patients and 61.5 years ...


Clinicopathological Significance Of Common Genetic Alterations In Patients With Acute Promyelocytic Leukemia, Sukanta Nath, Jina Bhattacharyya, Prem Chandra, Renu Saxena, Sudha Sazawal, Kandarpa Kumar Saikia 2022 Department of Bioengineering and Technology, Gauhati University, Guwahati, Assam, India

Clinicopathological Significance Of Common Genetic Alterations In Patients With Acute Promyelocytic Leukemia, Sukanta Nath, Jina Bhattacharyya, Prem Chandra, Renu Saxena, Sudha Sazawal, Kandarpa Kumar Saikia

Hematology/Oncology and Stem Cell Therapy

Objective/Background: Acute myeloid leukemia (AML) is one of the common forms of hematological malignancy and acute promyelocytic leukemia (APL) is a unique subtype of AML conferring favorable prognosis. We aimed to determine the prevalence and prognostic impact of Fms-like tyrosine kinase 3 (FLT3), nucleophosmin 1 (NPM1) mutation, epidermal growth factor receptor (EGFR), and flow marker’s expression in patients with APL. Methods: In the present study, 165 de novo APL patients were molecularly characterized for promyelocytic leukemia (PML) breakpoint and additional genetic alterations. Reverse transcriptase polymerase chain reaction (PCR) and real time PCR assays were used to detect genetic ...


Impact Of The Major Bcr-Abl1 Transcript Type On Clinical And Biological Parameters And Molecular Response In Patients With Chronic Myeloid Leukemia, Mourad Nachi, Ibtissem Kihel, Badra Entasoltane, Mohamed Brahimi, Nabil Yafour, Djaoued Guella, Amine Abed, Mohamed A. Bekadja 2022 Faculty of Medicine, Ahmed Ben Bella University of Oran, Algeria

Impact Of The Major Bcr-Abl1 Transcript Type On Clinical And Biological Parameters And Molecular Response In Patients With Chronic Myeloid Leukemia, Mourad Nachi, Ibtissem Kihel, Badra Entasoltane, Mohamed Brahimi, Nabil Yafour, Djaoued Guella, Amine Abed, Mohamed A. Bekadja

Hematology/Oncology and Stem Cell Therapy

Aim: In chronic myeloid leukemia (CML), the impact of MBCR-ABL1 major transcript type on disease phenotype and response to treatment still controversial to date. This work aims to study the influence of Mb3a2 and Mb2a2 transcripts on clinico-biological parameters and the molecular response in patients with chronic phase chronic myeloid leukemia (CP-CML) treated with Imatinib as frontline therapy. Methods: This is six years prospective study started in March 1 st, 2013. 67 patients with newly CP-CML were treated by Imatinib as frontline therapy. Clinical and biological characteristics disease were collected for all patients. Molecular typing was performed by multiplex RT-PCR ...


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