Medicine and Health Sciences Commons^™

The Global Burden Of Adolescent And Young Adult Cancer In 2019: A Systematic Analysis For The Global Burden Of Disease Study 2019, Elysia M. Alvarez, Lisa M. Force, Rixing Xu, Kelly Compton, Dan Lu, Ismaeel Yunusa Ph. D., Et Al.

Faculty Publications

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Background

In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15–39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults.

Methods

Using the GBD 2019 methodology, international mortality data were collected …

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Prolonged Time From Diagnosis To Breast-Conserving Surgery Is Associated With Upstaging In Hormone Receptor-Positive Invasive Ductal Breast Carcinoma, Natalie Hills, Macall Leslie, Rachel Davis, Marielle Crowell, Hiroyasu Kameyama, Hallgeir Rui, Inna Chervoneva, William Dooley, Takemi Tanaka

Faculty Publications

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BACKGROUND: Time to surgery (TTS) has been suggested to have an association with mortality in early-stage breast cancer. OBJECTIVE: This study aims to determine the association between TTS and preoperative disease progression in tumor size or nodal status among women diagnosed with clinical T1N0M0 ductal breast cancer. METHODS: Women diagnosed with clinical T1N0M0 ductal breast cancer who had breast-conserving surgery as their first definitive treatment between 2010 and 2016 (n = 90,405) were analyzed using the National Cancer Database. Separate multivariable logistic regression models for hormone receptor (HR)-positive and HR-negative patients, adjusted for clinical and demographic variables, were used to …

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The Development Of Novel Cdk8 And Cdk19 Inhibitors And Degraders As Potential Anti-Cancer Agents, Li Zhang

Theses and Dissertations

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CDK8 and its homolog CDK19 are essential for transcription regulation and their dysregulation has been identified in numerous diseases, especially in cancers. CDK8 and CDK19 have been implicated in cancer development through their kinase activity and kinase independent functions. Despite the existing CDK8/19 inhibitors, there is still a need to develop novel CDK8/19 inhibitors with improved potency and PK profile. It is also necessary to develop CDK8/19 degraders that are able to eliminate the kinase-independent functions. Although two CDK8-degrading PROteolysis Activating Chimeras (PROTACs) have been reported, they have limited CDK8 degradation efficacy and no effect on CDK19. PROTACs with improved …

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Clinical Correlations Of Polycomb Repressive Complex 2 In Different Tumor Types, Maksim Erokhin, Olga Chetverina, Balázs Győrffy, Victor V. Tatarskiy, Vladic Mogila, Alexander A. Shtil, Igor Roninson, Jerome Moreaux, Pavel Georgiev, Giacomo Cavalli, Darya Chetverina

Faculty Publications

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PRC2 (Polycomb repressive complex 2) is an evolutionarily conserved protein complex required to maintain transcriptional repression. The core PRC2 complex includes EZH2, SUZ12, and EED proteins and methylates histone H3K27. PRC2 is known to contribute to carcinogenesis and several small molecule inhibitors targeting PRC2 have been developed. The present study aimed to identify the cancer types in which PRC2 targeting drugs could be beneficial. We queried genomic and transcriptomic (cBioPortal, KMplot) database portals of clinical tumor samples to evaluate clinical correlations of PRC2 subunit genes. EZH2, SUZ12, and EED gene amplification was most frequently found in prostate cancer, whereas lymphoid …

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Association Of Cumulative Social Risk And Social Support With Receipt Of Chemotherapy Among Patients With Advanced Colorectal Cancer, Rachel E. Davis, Amber W. Trickey, Paul Abrahamse, Ikuko Kato, Kevin Ward, Arden M. Morris

Faculty Publications

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Importance: Approximately 38% of patients with advanced colorectal cancer do not receive chemotherapy. Objective: To determine whether cumulative social risk (ie, multiple co-occurring sociodemographic risk factors) is associated with lower receipt of chemotherapy among patients with advanced colorectal cancer and whether social support would moderate this association. Design, Setting, and Participants: This cross-sectional, population-based, mailed survey study was conducted from 2012 to 2014. Participants were recruited between 2011 and 2014 from all adults within 1 year after diagnosis of stage III colorectal cancer in the Detroit, Michigan, and State of Georgia Surveillance, Epidemiology, End-Results cancer registries. Patients were eligible if …

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Dietary Inflammatory Index Is Related To Heart Failure Risk And Cardiac Function: A Case-Control Study In Heart Failure Patients, Jalal Moludi, Nitin Shivappa Mbbs, Mph, Ph.D., Soghra Alisgharzadeh, James R. Hébert Scd, Mohammad Alizadeh

Faculty Publications

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Aims: Previous studies suggest that diet and inflammation are important risk factors for heart failure (HF); however, the associations remain unclear. The Dietary Inflammatory Index (DII®) was established to measure the inflammatory capacity of individuals' diet. This study aimed to explore the DII in HF subjects compared with controls. Methods and Results: We conducted a case–control (116 cases and 113 controls) study that recruited in the similar clinics. DII scores were calculated based on dietary intakes. N-Terminal pro-brain natriuretic peptide (NT-proBNP) levels and ejection fraction (EF) were assessed in both groups. In order to analyze DII scores with HF as …

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A Multilevel And Spatial Analysis Of Oral And Pharyngeal Cancer In South Carolina, Deborah M. Hurley

Theses and Dissertations

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Objective: Disparities in the distribution of oral and pharyngeal cancer exist worldwide. This is also true in the United States and in South Carolina. Differences exist in oral and pharyngeal cancer stage and survival by race and sex, with higher incidence rates for Whites but higher proportions of late-stage cancer and lower survival for Blacks. This study was conducted to evaluate whether any differences exist in the spatial distribution of oral and pharyngeal cancer stage at diagnosis and survival, and to evaluate the association of income inequality, material deprivation and other measures of social determinants of health (contextual risk factors) …

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Design And Synthesis Of Macrocyclic Peptide Braf-Wt Dimerization Inhibitors For The Treatment Of Metastatic Melanoma, Chad Mulloy Beneker

Theses and Dissertations

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In cases of metastatic melanoma, BRAF is frequently mutated to the V600E oncoprotein causing uncontrolled cell proliferation driven by the MAPK-ERK pathway. There are several BRAF inhibitors, such as vemurafenib, which are FDA approved, but patients treated with these Type-I kinase inhibitors frequently observe relapse under mutant RAS and BRAF-wt conditions due to paradoxical activation. The mechanism of this resistance occurs through binding of the inhibitor to BRAF-wt initiating conformational changes which leads to BRAF dimerization. Once in the dimerized state, the inhibited monomer induces allosteric transactivation of the second monomer. This drug-induced activation of BRAF in cells with mutant …

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