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Full-Text Articles in Medicine and Health Sciences

Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart Jun 2023

Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Graduate Studies Faculty Publications

Myeloid immune cells (MICs) are potent innate immune cells serving as first responders to invading pathogens and internal changes to cellular homeostasis. Cancer is a stage of altered cellular homeostasis that can originate in response to different pathogens, chemical carcinogens, and internal genetic/epigenetic changes. MICs express several pattern recognition receptors (PRRs) on their membranes, cytosol, and organelles, recognizing systemic, tissue, and organ-specific altered homeostasis. cGAS/STING signaling is a cytosolic PRR system for identifying cytosolic double-stranded DNA (dsDNA) in a sequence-independent but size-dependent manner. The longer the cytosolic dsDNA size, the stronger the cGAS/STING signaling activation with increased type 1 interferon …


Covid-19 Severity And Cardiovascular Outcomes In Sars-Cov-2-Infected Patients With Cancer And Cardiovascular Disease, Melissa Y.Y. Moey, Cassandra Hennessy, Benjamin French, Jeremy L. Warner, Matthew D. Tucker, Daniel J. Hausrath, Dimpy P. Shah, Jeanne M. Decara, Ziad Bakouny, Chris Labaki, Toni K. Choueiri, Susan Dent, Nausheen Akhter, Roohi Ismail-Khan, Lisa Tachiki, David Slosky, Tamar S. Polonsky, Joy A. Awosika, Audrey Crago, Trisha Wise-Draper, Nino Balanchivadze, Clara Hwang, Leslie A. Fecher, Cyndi Gonzalez Gomez, Brandon Hayes-Lattin, Michael J. Glover, Sumit A. Shah, Dharmesh Gopalakrishnan, Elizabeth A. Griffiths, Daniel H. Kwon, Vadim S. Koshkin, Sana Mahmood, Babar Bashir, Taylor Nonato, Pedram Razavi, Rana R. Mckay, Gayathri Nagaraj, Eric Oligino, Matthew Puc, Polina Tregubenko, Elizabeth M. Wulff-Burchfield, Zhuoer Xie, Thorvardur R. Halfdanarson, Dimitrios Farmakiotis, Elizabeth J. Klein, Elizabeth V. Robilotti, Gregory J. Riely, Jean-Bernard Durand, Salim S. Hayek, Lavanya Kondapalli, Stephanie Berg, Timothy E. O'Connor, Mehmet A. Bilen, Cecilia Castellano, Melissa K. Accordino, Blau Sibel, Lisa B. Weissmann, Chinmay Jani, Daniel B. Flora, Lawrence Rudski, Miriam Santos Dutra, Bouganim Nathaniel, Erika Ruíz-García, Diana Vilar-Compte, Shilpa Gupta, Alicia Morgans, Anju Nohria Jun 2023

Covid-19 Severity And Cardiovascular Outcomes In Sars-Cov-2-Infected Patients With Cancer And Cardiovascular Disease, Melissa Y.Y. Moey, Cassandra Hennessy, Benjamin French, Jeremy L. Warner, Matthew D. Tucker, Daniel J. Hausrath, Dimpy P. Shah, Jeanne M. Decara, Ziad Bakouny, Chris Labaki, Toni K. Choueiri, Susan Dent, Nausheen Akhter, Roohi Ismail-Khan, Lisa Tachiki, David Slosky, Tamar S. Polonsky, Joy A. Awosika, Audrey Crago, Trisha Wise-Draper, Nino Balanchivadze, Clara Hwang, Leslie A. Fecher, Cyndi Gonzalez Gomez, Brandon Hayes-Lattin, Michael J. Glover, Sumit A. Shah, Dharmesh Gopalakrishnan, Elizabeth A. Griffiths, Daniel H. Kwon, Vadim S. Koshkin, Sana Mahmood, Babar Bashir, Taylor Nonato, Pedram Razavi, Rana R. Mckay, Gayathri Nagaraj, Eric Oligino, Matthew Puc, Polina Tregubenko, Elizabeth M. Wulff-Burchfield, Zhuoer Xie, Thorvardur R. Halfdanarson, Dimitrios Farmakiotis, Elizabeth J. Klein, Elizabeth V. Robilotti, Gregory J. Riely, Jean-Bernard Durand, Salim S. Hayek, Lavanya Kondapalli, Stephanie Berg, Timothy E. O'Connor, Mehmet A. Bilen, Cecilia Castellano, Melissa K. Accordino, Blau Sibel, Lisa B. Weissmann, Chinmay Jani, Daniel B. Flora, Lawrence Rudski, Miriam Santos Dutra, Bouganim Nathaniel, Erika Ruíz-García, Diana Vilar-Compte, Shilpa Gupta, Alicia Morgans, Anju Nohria

Kimmel Cancer Center Faculty Papers

BACKGROUND: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited.

OBJECTIVES: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF.

METHODS: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD

RESULTS: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity …


Device Assessed Activity Behaviours In Patients With Indwelling Pleural Catheter: A Sub-Study Of The Australasian Malignant Pleural Effusion (Ample)-2 Randomized Trial, Carolyn J. Peddle-Mcintyre, Sanjeevan Muruganandan, Joanne Mcveigh, Deirdre B. Fitzgerald, Leon Straker, Robert U. Newton, Kevin Murray, Yun Chor Gary Lee Jun 2023

Device Assessed Activity Behaviours In Patients With Indwelling Pleural Catheter: A Sub-Study Of The Australasian Malignant Pleural Effusion (Ample)-2 Randomized Trial, Carolyn J. Peddle-Mcintyre, Sanjeevan Muruganandan, Joanne Mcveigh, Deirdre B. Fitzgerald, Leon Straker, Robert U. Newton, Kevin Murray, Yun Chor Gary Lee

Research outputs 2022 to 2026

Background and Objective: Device-assessed activity behaviours are a novel measure for comparing intervention outcomes in patients with malignant pleural effusion (MPE). Australasian Malignant PLeural Effusion (AMPLE)-2 was a multi-centre clinical trial where participants with MPE treated with an indwelling pleural catheter were randomized to daily (DD) or symptom-guided (SGD) drainage for 60-days. Our aim was to describe activity behaviour patterns in MPE patients, explore the impact of drainage regimen on activity behaviours and examine associations between activity behaviours and quality of life (QoL). Methods: Following randomization to DD or SGD, participants enrolled at the lead site (Perth) completed accelerometry assessment. …


Immunometabolic Reprogramming, Another Cancer Hallmark, Vijay Kumar, John H. Stewart May 2023

Immunometabolic Reprogramming, Another Cancer Hallmark, Vijay Kumar, John H. Stewart

School of Medicine Faculty Publications

Molecular carcinogenesis is a multistep process that involves acquired abnormalities in key biological processes. The complexity of cancer pathogenesis is best illustrated in the six hallmarks of the cancer: (1) the development of self-sufficient growth signals, (2) the emergence of clones that are resistant to apoptosis, (3) resistance to the antigrowth signals, (4) neo-angiogenesis, (5) the invasion of normal tissue or spread to the distant organs, and (6) limitless replicative potential. It also appears that non-resolving inflammation leads to the dysregulation of immune cell metabolism and subsequent cancer progression. The present article delineates immunometabolic reprogramming as a critical hallmark of …


Guaranteed Income And Financial Treatment Trial (Gift Trial Or Giftt): A 12-Month, Randomized Controlled Trial To Compare The Effectiveness Of Monthly Unconditional Cash Transfers To Treatment As Usual In Reducing Financial Toxicity In People With Cancer Who Have Low Incomes, Meredith Doherty, Jonathan Heintz, Amy Leader, David Wittenburg, Yonatan Ben-Shalom, Jessica Jacoby, Amy Castro, Stacia West May 2023

Guaranteed Income And Financial Treatment Trial (Gift Trial Or Giftt): A 12-Month, Randomized Controlled Trial To Compare The Effectiveness Of Monthly Unconditional Cash Transfers To Treatment As Usual In Reducing Financial Toxicity In People With Cancer Who Have Low Incomes, Meredith Doherty, Jonathan Heintz, Amy Leader, David Wittenburg, Yonatan Ben-Shalom, Jessica Jacoby, Amy Castro, Stacia West

Department of Medical Oncology Faculty Papers

Cancer-related financial hardship (i.e., financial toxicity) has been associated with anxiety and depression, greater pain and symptom burden, treatment nonadherence, and mortality. Out-of-pocket healthcare costs and lost income are primary drivers of financial toxicity, however, income loss is a pronounced risk factor for cancer patients with low incomes. There has been little progress in developing an income intervention to alleviate financial toxicity cancer patients with low incomes. Unconditional cash transfers (UCT), or guaranteed income, have produced positive health effects in experiments with general low-income populations, but have not yet been evaluated in people with cancer. The Guaranteed Income and Financial …


Protocol For The Promoting Resilience In Stress Management (Prism) Intervention: A Multi-Site Randomized Controlled Trial For Adolescents And Young Adults With Advanced Cancer, Alison O’Daffer, Liam Comiskey, Samantha R. Scott, Chuan Zhou, Miranda C. Bradford, Joyce P. Yi-Frazier, Abby R. Rosenberg May 2023

Protocol For The Promoting Resilience In Stress Management (Prism) Intervention: A Multi-Site Randomized Controlled Trial For Adolescents And Young Adults With Advanced Cancer, Alison O’Daffer, Liam Comiskey, Samantha R. Scott, Chuan Zhou, Miranda C. Bradford, Joyce P. Yi-Frazier, Abby R. Rosenberg

Psychology: Faculty Scholarship

Background

Adolescents and young adults (AYAs) with cancer are at high risk of poor psychosocial outcomes, and evidence-based interventions designed to meet their psychosocial and communication needs are lacking. The main objective of this project is to test the efficacy of a new adaptation of the Promoting Resilience in Stress Management intervention for AYAs with Advanced Cancer (PRISM-AC).

Methods/design

The PRISM-AC trial is a 2-arm, parallel, non-blinded, multisite, randomized controlled trial. 144 participants with advanced cancer will be enrolled and randomized to either usual, non-directive, supportive care without PRISM-AC (“control” arm) or with PRISM-AC (“experimental” arm). PRISM is a manualized, …


Benefits And Risks Of Sun Exposure To Maintain Adequate Vitamin D Levels., Jonathan Raymond-Lezman, Suzanne Riskin M.D. May 2023

Benefits And Risks Of Sun Exposure To Maintain Adequate Vitamin D Levels., Jonathan Raymond-Lezman, Suzanne Riskin M.D.

HPD Articles

Vitamin D is a hormone that can be generated in the skin upon ultraviolet light exposure or ingested through supplementation. Vitamin D deficiency may have numerous deleterious effects on health. Sun avoidance strategies should be avoided due to the unwanted health risks associated with hypovitaminosis D. We present an objective investigation of the benefits and risks of using sun exposure to increase vitamin D levels and how it impacts human health. A review of the literature was conducted using Embase and PubMed to examine the relationship between UV exposure, vitamin D levels, health benefits, and risks. UV exposure is the …


A Review Of How Bioinformatics And Genome Sequencing Are Affecting Precision Medicine, Taylor S. Hickey May 2023

A Review Of How Bioinformatics And Genome Sequencing Are Affecting Precision Medicine, Taylor S. Hickey

Honors Theses

Advancement in genomic sequencing and bioinformatics methods have been affecting biomedical research through precision medicine, especially in the area of cancer. Vaccine therapies can be developed using neoantigens that target specific mutations in tumors. The goals of this research are to identify mutations that lead to cancer and then define subpopulations in which patients can easily be identified. The future goal is to have targeted vaccines that are specific to each subpopulation ready to be used in treatment of their cancer. Limitations to reaching these goals have been due to tumor heterogeneity, cancer location, and difficulty in creating neoantigens for …


Highlights From The Second Choosing Wisely Africa Conference: A Roadmap To Value-Based Cancer Care In East Africa (9–10 February 2023, Dar Es Salaam, Tanzania), Rugengamanzi Eulade, Godwin Abdiel Nnko, Jerry Ndumbalo, Nazima Dharsee, Larry O. Akoko, Christian Ntizimira, Beda Likonda, Harrison Chuwa, Salum Lidenge, Verna Vanderpuye, Nazik Hammad, Sikudhani Muya, Rubagumya Rubagumya May 2023

Highlights From The Second Choosing Wisely Africa Conference: A Roadmap To Value-Based Cancer Care In East Africa (9–10 February 2023, Dar Es Salaam, Tanzania), Rugengamanzi Eulade, Godwin Abdiel Nnko, Jerry Ndumbalo, Nazima Dharsee, Larry O. Akoko, Christian Ntizimira, Beda Likonda, Harrison Chuwa, Salum Lidenge, Verna Vanderpuye, Nazik Hammad, Sikudhani Muya, Rubagumya Rubagumya

Internal Medicine, East Africa

The ecancer Choosing Wisely conference was held for the second time in Africa in Dar es Salaam, Tanzania, from the 9th to 10th of February 2023. ecancer in collaboration with the Tanzania Oncology Society organised this conference which was attended by more than 150 local and international delegates. During the 2 days of the conference, more than ten speakers from different specialties in the field of oncology gave insights into Choosing Wisely in oncology. Topics from all fields linked to cancer care such as radiation oncology, medical oncology, prevention, oncological surgery, palliative care, patient advocacy, pathology, radiology, clinical trials, research …


A Dna-Peptide Crosslink (Dpc) Increases Mutagenicity In Sos-Induced Escherichia Coli, Alessandra Bassani May 2023

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, …


Deletion Of The Mrna Stability Factor Elavl1 (Hur) In Pancreatic Cancer Cells Disrupts The Tumor Microenvironment Integrity, Grace A Mccarthy, Roberto Di Niro, Jennifer M Finan, Aditi Jain, Yifei Guo, Cory R Wyatt, Alexander R Guimaraes, Trent A Waugh, Dove Keith, Terry K Morgan, Rosalie C Sears, Jonathan R Brody Apr 2023

Deletion Of The Mrna Stability Factor Elavl1 (Hur) In Pancreatic Cancer Cells Disrupts The Tumor Microenvironment Integrity, Grace A Mccarthy, Roberto Di Niro, Jennifer M Finan, Aditi Jain, Yifei Guo, Cory R Wyatt, Alexander R Guimaraes, Trent A Waugh, Dove Keith, Terry K Morgan, Rosalie C Sears, Jonathan R Brody

Department of Surgery Faculty Papers

Stromal cells promote extensive fibrosis in pancreatic ductal adenocarcinoma (PDAC), which is associated with poor prognosis and therapeutic resistance. We report here for the first time that loss of the RNA-binding protein human antigen R (HuR, ELAVL1) in PDAC cells leads to reprogramming of the tumor microenvironment. In multiple in vivo models, CRISPR deletion of ELAVL1 in PDAC cells resulted in a decrease of collagen deposition, accompanied by a decrease of stromal markers (i.e. podoplanin, αsmooth muscle actin, desmin). RNA-sequencing data showed that HuR plays a role in cell–cell communication. Accordingly, cytokine arrays identified that HuR regulates the secretion of …


Anti-Cancer Effect Of Cissus Quadrangularis On Human Glioblastoma Cells, Benxu Cheng, Yunlin Wei, Lili Guerra, Rozena Shirvani-Arani, Santiago Balderas, Laura Valdez, Andrew Tsin, Xiaoqian Fang Apr 2023

Anti-Cancer Effect Of Cissus Quadrangularis On Human Glioblastoma Cells, Benxu Cheng, Yunlin Wei, Lili Guerra, Rozena Shirvani-Arani, Santiago Balderas, Laura Valdez, Andrew Tsin, Xiaoqian Fang

School of Medicine Publications and Presentations

Objectives

Glioblastoma multiforme (GBM) is a common and fatal brain tumour in the central nervous system with a poor survival rate and a median survival time of 15 months only. The standard treatment is aggressive surgical resection followed by radiotherapy and chemotherapy. However, effective drugs available in chemotherapy are limited. This study was designed to evaluate, for the first time, the potential therapeutic effect of Cissus quadrangularis (CQ) in human glioblastoma cells and to investigate its possible mechanisms of action. Methods

In this study, we examined the anticancer activity of CQ in human glioblastoma U87 MG cells by cell viability …


The Effects Of Tert-Butyl Hydroquinone (Tbhq) On Estrogen Receptor Alpha (Erα) And Tumor Suppressor Protein P53 In T-47d And Mcf-7 Breast Cancer Cell Lines, Samantha E. Pfiffner, Katelyn Farrar, Erin Hallman, Kaylin Whittaker, Aisha Zanib, Sumi Dinda Ph.D. Mar 2023

The Effects Of Tert-Butyl Hydroquinone (Tbhq) On Estrogen Receptor Alpha (Erα) And Tumor Suppressor Protein P53 In T-47d And Mcf-7 Breast Cancer Cell Lines, Samantha E. Pfiffner, Katelyn Farrar, Erin Hallman, Kaylin Whittaker, Aisha Zanib, Sumi Dinda Ph.D.

Medical Student Research Symposium

Tert-butyl hydroquinone (TBHQ) is an aromatic compound that is commonly used as a preservative in processed food to prevent rancidity and lengthen shelf life. TBHQ is known to act as an antioxidant by protecting cells from radical oxygen species and thus preventing DNA damage. Although previous studies have found TBHQ to cause cancer cell death at high concentrations, they have also contrastingly found TBHQ, when studied in animal models, to enhance carcinogenic effects. However, the effect of TBHQ on breast cancer has not been thoroughly explored. With the prevalence of breast cancer and the wide use of TBHQ in processed …


Risk And Resilient Functioning Of Families Of Children With Cancer During The Covid-19 Pandemic., Renee Gilbert, Carolyn R Bates, Devanshi Khetawat, Meredith Dreyer Gillette, Rachel Moore Mar 2023

Risk And Resilient Functioning Of Families Of Children With Cancer During The Covid-19 Pandemic., Renee Gilbert, Carolyn R Bates, Devanshi Khetawat, Meredith Dreyer Gillette, Rachel Moore

Manuscripts, Articles, Book Chapters and Other Papers

Previous literature highlights the impact of COVID-19 on family functioning. Less is known about the impact of the pandemic on families of pediatric cancer patients. In order to determine universal and unique risk and resilience factors of these families during the pandemic, a qualitative analysis was conducted on families currently receiving cancer treatment at a Midwestern hospital. Results of the data analysis depict ways in which these families have been impacted by and have adapted to COVID-19. These findings suggest that families of pediatric cancer patients have unique experiences in the context of COVID-19, in addition to universal experiences outlined …


Interactions Between Silica And Titanium Nanoparticles And Oral And Gastrointestinal Epithelia: Consequences For Inflammatory Diseases And Cancer, Cassio Luiz Coutinho Almeida-Da-Silva, Leticia Ferreira Cabido, Wei Chun Chin, Ge Wang, David M. Ojcius, Changqing Li Mar 2023

Interactions Between Silica And Titanium Nanoparticles And Oral And Gastrointestinal Epithelia: Consequences For Inflammatory Diseases And Cancer, Cassio Luiz Coutinho Almeida-Da-Silva, Leticia Ferreira Cabido, Wei Chun Chin, Ge Wang, David M. Ojcius, Changqing Li

All Dugoni School of Dentistry Faculty Articles

Engineered nanoparticles (NPs) composed of elements such as silica and titanium, smaller than 100 nm in diameter and their aggregates, are found in consumer products such as cosmetics, food, antimicrobials and drug delivery systems, and oral health products such as toothpaste and dental materials. They may also interact accidently with epithelial tissues in the intestines and oral cavity, where they can aggregate into larger particles and induce inflammation through pathways such as inflammasome activation. Persistent inflammation can lead to precancerous lesions. Both the particles and lesions are difficult to detect in biopsies, especially in clinical settings that screen large numbers …


Association Of Computed Tomography Measures Of Muscle And Adipose Tissue And Progressive Changes Throughout Treatment With Clinical Endpoints In Patients With Advanced Lung Cancer Treated With Immune Checkpoint Inhibitors, Azim Khan, Christopher J. Welman, Afaf Abed, Susan O’Hanlon, Andrew Redfern, Sara Azim, Pedro Lopez, Favil Singh, Adnan Khattak Mar 2023

Association Of Computed Tomography Measures Of Muscle And Adipose Tissue And Progressive Changes Throughout Treatment With Clinical Endpoints In Patients With Advanced Lung Cancer Treated With Immune Checkpoint Inhibitors, Azim Khan, Christopher J. Welman, Afaf Abed, Susan O’Hanlon, Andrew Redfern, Sara Azim, Pedro Lopez, Favil Singh, Adnan Khattak

Research outputs 2022 to 2026

To investigate the association between skeletal muscle mass and adiposity measures with disease-free progression (DFS) and overall survival (OS) in patients with advanced lung cancer receiving immunotherapy, we retrospectively analysed 97 patients (age: 67.5 ± 10.2 years) with lung cancer who were treated with immunotherapy between March 2014 and June 2019. From computed tomography scans, we assessed the radiological measures of skeletal muscle mass, and intramuscular, subcutaneous and visceral adipose tissue at the third lumbar vertebra. Patients were divided into two groups based on specific or median values at baseline and changes throughout treatment. A total number of 96 patients …


Congenital Gastrointestinal Anomalies In Europe 2010–2019: A Geo-Spatiotemporal And Causal Inferential Study Of Epidemiological Patterns In Relationship To Cannabis- And Substance Exposure, Albert Stuart Reece, Gary Kenneth Hulse Mar 2023

Congenital Gastrointestinal Anomalies In Europe 2010–2019: A Geo-Spatiotemporal And Causal Inferential Study Of Epidemiological Patterns In Relationship To Cannabis- And Substance Exposure, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Introduction: Congenital anomalies (CA’s) of most of the gastrointestinal tract have been linked causally with prenatal or community cannabis exposure. Therefore, we studied this relationship in Europe. Methods: CA data were from Eurocat. Drug-use data were sourced from the European Monitoring Centre for Drugs and Drug Addiction. Income data were taken from the World Bank. Results: When countries with increasing rates of daily cannabis use were compared with those which were not, the overall rate of gastrointestinal CA’s (GCA’s) was higher in the former group (p = 0.0032). The five anomalies which were related to the metrics of cannabis exposure …


Modified Linear Peptides Effectively Silence Stat-3 In Breast Cancer And Ovarian Cancer Cell Lines, Dindyal Mandal, Sandeep Lohan, Muhammad Imran Sajid, Abdulelah Alhazza, Rakesh Kumar Tiwari, Keykavous Parang, Hamidreza Montazeri Aliabadi Feb 2023

Modified Linear Peptides Effectively Silence Stat-3 In Breast Cancer And Ovarian Cancer Cell Lines, Dindyal Mandal, Sandeep Lohan, Muhammad Imran Sajid, Abdulelah Alhazza, Rakesh Kumar Tiwari, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

RNA interference (RNAi) has drawn enormous attention as a powerful tool because of its capability to interfere with mRNA and protein production. However, designing a safe and efficient delivery system in RNAi therapeutics remains challenging. Herein, we have designed and synthesized several linear peptides containing tryptophan (W) and arginine (R) residues separated by the β-alanine (βA) spacer and attached to a lipophilic fatty acyl chain, cholesterol, or PEG. The peptide backbone sequences were: Ac-C-βA-βA-W4-βA-βA-R4-CO-NH2 and Ac-K-βA-βA-W4-βA-βA-R4-CO-NH2, with only a difference in N-terminal amino acid. The cysteine side chain in the first sequence was used for the conjugation with PEG2000 and …


Patterns Of Cannabis- And Substance-Related Congenital General Anomalies In Europe: A Geospatiotemporal And Causal Inferential Study, Albert Stuart Reece, Gary Kenneth Hulse Feb 2023

Patterns Of Cannabis- And Substance-Related Congenital General Anomalies In Europe: A Geospatiotemporal And Causal Inferential Study, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Introduction:

Recent series of congenital anomaly (CA) rates (CARs) have showed the close and epidemiologically causal relationship of cannabis exposure to many CARs. We investigated these trends in Europe where similar trends have occurred.

Methods:

CARs from EUROCAT. Drug use from European Monitoring Centre for Drugs and Drug Addiction. Income data from World Bank. Results: CARs were higher in countries with increasing daily use overall (p = 9.99 × 10−14, minimum E-value (mEV) = 2.09) and especially for maternal infections, situs inversus, teratogenic syndromes and VACTERL syndrome (p = 1.49 × 10−15, mEV = 3.04). In …


Geospatiotemporal And Causal Inferential Study Of European Epidemiological Patterns Of Cannabis- And Substance-Related Congenital Orofacial Anomalies, Albert Stuart Reece, Gary Kenneth Hulse Feb 2023

Geospatiotemporal And Causal Inferential Study Of European Epidemiological Patterns Of Cannabis- And Substance-Related Congenital Orofacial Anomalies, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Introduction:

Since high rates of congenital anomalies (CAs), including facial CAs (FCAs), causally attributed to antenatal and community cannabis use have been reported in several recent series, it was of interest to examine this subject in detail in Europe.

Methods:

CA data were taken from the EUROCAT database. Drug exposure data were downloaded from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Income was taken from the World Bank’s online sources.

Results:

On the bivariate maps of both orofacial clefts and holoprosencephaly against resin, the Δ9-tetrahydrocannabinol concentration rates of both covariates increased together in France, Bulgaria, and the …


Clinical Epigenomic Explanation Of The Epidemiology Of Cannabinoid Genotoxicity Manifesting As Transgenerational Teratogenesis, Cancerogenesis And Aging Acceleration, Albert Stuart Reece, Gary Kenneth Hulse Feb 2023

Clinical Epigenomic Explanation Of The Epidemiology Of Cannabinoid Genotoxicity Manifesting As Transgenerational Teratogenesis, Cancerogenesis And Aging Acceleration, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

As global interest in the therapeutic potential of cannabis and its’ derivatives for the management of selected diseases increases, it is increasingly imperative that the toxic profile of cannabinoids be thoroughly understood in order to correctly assess the balance between the therapeutic risks and benefits. Modern studies across a number of jurisdictions, including Canada, Australia, the US and Europe have confirmed that some of the most worrying and severe historical reports of both congenital anomalies and cancer induction following cannabis exposure actually underestimate the multisystem thousand megabase-scale transgenerational genetic damage. These findings from teratogenic and carcinogenic literature are supported by …


Editorial: Hallmark Of Cancer: Reprogramming Of Cellular Metabolism, Baljinder Kaur, Yahya Sohrabi, Abhinav Achreja, Michael P. Lisanti, Ubaldo Emilio Martinez-Outshoorn Jan 2023

Editorial: Hallmark Of Cancer: Reprogramming Of Cellular Metabolism, Baljinder Kaur, Yahya Sohrabi, Abhinav Achreja, Michael P. Lisanti, Ubaldo Emilio Martinez-Outshoorn

Department of Medical Oncology Faculty Papers

No abstract provided.


Identification Of Tp53 Mutations In Circulating Tumour Dna In High Grade Serous Ovarian Carcinoma Using Next Generation Sequencing Technologies, Leslie Calapre, Tindaro Giardina, Aaron B. Beasley, Anna L. Reid, Colin Stewart, Benhur Amanuel, Tarek M. Meniawy, Elin S. Gray Jan 2023

Identification Of Tp53 Mutations In Circulating Tumour Dna In High Grade Serous Ovarian Carcinoma Using Next Generation Sequencing Technologies, Leslie Calapre, Tindaro Giardina, Aaron B. Beasley, Anna L. Reid, Colin Stewart, Benhur Amanuel, Tarek M. Meniawy, Elin S. Gray

Research outputs 2022 to 2026

Plasma circulating tumour DNA (ctDNA) has been suggested to be a viable biomarker of response to treatment in patients with high grade serous ovarian carcinoma (HGSOC). TP53 mutations are present in more than 90 % of HGSOCs but somatic variants are distributed across all exonic regions of the gene, requiring next generation sequencing (NGS) technologies for mutational analysis. In this study, we compared the suitability of the Accel (Swift) and Oncomine (ThermoFisher) panels for identification of TP53 mutations in ctDNA of HGSOC patients (N = 10). Only 6 patients (60 %) were found to have TP53 mutations using the ACCEL …


Three-Dimensional (3d) In Vitro Cell Culture Protocols To Enhance Glioblastoma Research, Janith Wanigasekara, Lara Carroll, Patrick J. Cullen, Brijesh K. Tiwari, James Curtin Jan 2023

Three-Dimensional (3d) In Vitro Cell Culture Protocols To Enhance Glioblastoma Research, Janith Wanigasekara, Lara Carroll, Patrick J. Cullen, Brijesh K. Tiwari, James Curtin

Articles

Three-dimensional (3D) cell culture models can help bridge the gap between in vitro cell cultures and in vivo responses by more accurately simulating the natural in vivo environment, shape, tissue stiffness, stressors, gradients and cellular response while avoiding the costs and ethical concerns associated with animal models. The inclusion of the third dimension in 3D cell culture influences the spatial organization of cell surface receptors that interact with other cells and imposes physical restrictions on cells in compared to Two-dimensional (2D) cell cultures. Spheroids’ distinctive cyto-architecture mimics in vivo cellular structure, gene expression, metabolism, proliferation, oxygenation, nutrition absorption, waste excretion, …


Nutritional Medicine: Education For Advanced Practice Providers, Natalie Organ Jan 2023

Nutritional Medicine: Education For Advanced Practice Providers, Natalie Organ

DNP Research Projects

Abstract

OBJECTIVE: The project's primary goal was to educate the APP and develop positive attitudes and beliefs concerning plant-based nutrition regarding obesity, diabetes, cardiovascular disease, and cancer. The project addressed a crucial gap in healthcare education. APPs were not routinely given the chance to learn nutritional medicine, leading to decreased confidence in providing nutritional guidance in clinical practice.

METHODS: The DNP project participants were practicing advanced practice providers. The Knowledge, Attitude, Behavior (KAB) education theory and CREATION Life were used. This project used Qualtrics to send a pre-and post-intervention survey titled Student Survey for Nutritional Medicine. The intervention was a …


Resveratrol, Gentisic Acid, And Flaxseed Oil: Antioxidative Agents Against Hela Cell Proliferation, Carson Krefft, Drake Teal, Raida Sugule, Suhaylah Marty Jan 2023

Resveratrol, Gentisic Acid, And Flaxseed Oil: Antioxidative Agents Against Hela Cell Proliferation, Carson Krefft, Drake Teal, Raida Sugule, Suhaylah Marty

Research and Scholarship Symposium Posters

This study examines how three dietary supplements—resveratrol, gentisic acid, and flaxseed oil—affect the growth of HeLa cells. Resveratrol was predicted to have a more significant inhibitory effect on HeLa cell proliferation than the other test substances. HeLa cells were expanded in T-25 flasks and treated in triplicate within 96 well plates with various supplement variables. The findings demonstrated that resveratrol promoted cell proliferation while gentisic acid and flaxseed oil treatment significantly reduced the viability of HeLa cells. The findings suggest that, in contrast to the hypothesis, resveratrol may not have much of an impact on reducing HeLa cell proliferation. HeLa …


Taste And Smell Abnormalities In Advanced Cancer: Negative Impact On Subjective Food Intake, Aidan O'Donoghue, Michelle Barrett, Pauline Uí Dhuibhir Pauline Uí Dhuibhir, Aileen Kennedy, Norma O'Leary, Declan Walshe Jan 2023

Taste And Smell Abnormalities In Advanced Cancer: Negative Impact On Subjective Food Intake, Aidan O'Donoghue, Michelle Barrett, Pauline Uí Dhuibhir Pauline Uí Dhuibhir, Aileen Kennedy, Norma O'Leary, Declan Walshe

Articles

Background: Taste and smell abnormalities (TSAs) are present in all cancer stages and may contribute to malnutrition. Despite this, they are rarely screened for. This study examined the prevalence and characteristics of TSAs and their influence on subjective food intake in advanced cancer. Methods: Consecutive patients with advanced cancer were recruited. A modified Taste and Smell Survey assessed subjective TSAs. Objective TSAs were assessed with validated taste strips and "Sniffin Sticks." A six-item food intake questionnaire identified any effect TSAs had on food preferences/aversions. Nutrition status was evaluated with the abridged Patient-Generated Subjective Global Assessment. Results: All 30 participants had …


Structural And Solution Speciation Studies On Selected [Cu(Nn)(Oo)] Complexes And An Investigation Of Their Biomimetic Activity, Ros Generation And Their Cytotoxicity In Normoxic, Hypoxic And Anoxic Environments In Mcf-7 Breast Cancer-Derived Cells, Hollie Jenkins Jan 2023

Structural And Solution Speciation Studies On Selected [Cu(Nn)(Oo)] Complexes And An Investigation Of Their Biomimetic Activity, Ros Generation And Their Cytotoxicity In Normoxic, Hypoxic And Anoxic Environments In Mcf-7 Breast Cancer-Derived Cells, Hollie Jenkins

Articles

Reactive oxygen species(ROS) generation with subsequent DNA damage is one of the principle mechanisms of action assigned to copper-based anticancer complexes. The efficacy of this type of chemotherapeutic may be reduced in the low oxygen environment of tumours. In this study the cytotoxicity of three complexes, [Cu(dips)(phen)] (1), [Cu(ph)(phen)]·2H2O (2) and [Cu(ph)(bpy)]·H2O (3) (disp: 3,5-diisopropylsalicylate, phen: 1,10- phenanthroline, ph: phthalate, bpy: 2,2′-bipyridyl) were assessed for anticancer activity in the breast-cancer derived MCF-7 line under normoxic, hypoxic and anoxic conditions. In an immortalised keratinocyte HaCaT cell line, the cytotoxicity of complexes 2 and 3 was significantly reduced under both normoxic and …


Health Disparities In Rural Kentucky Counties: Mortality Outcomes And The “Rural Penalty”, Aaron R. Tims Jan 2023

Health Disparities In Rural Kentucky Counties: Mortality Outcomes And The “Rural Penalty”, Aaron R. Tims

Scholarship in Medicine - All Papers

Objective: The object of this paper is to investigate the relationship between rurality and the national top five causes of death in Kentucky counties.

Methods: We used Spearman correlations to quantify the relationship between percent rurality and the crude death rate for heart disease, malignant neoplasia, unintentional injury, chronic lower respiratory disease, and cerebrovascular disease for each Kentucky county. We also used a Spearman correlation to compare and correlate percent rurality and mortality due to heart disease as these two factors changed between data from 2000 and 2010.

Results: Our research demonstrated statistically significant correlations between percent rurality and the …


Incidence And Mortality Of Uveal Melanoma In Australia (1982–2014), Aaron B. Beasley, David B. Preen, Samuel Mclenachan, Elin S. Gray, Fred K. Chen Jan 2023

Incidence And Mortality Of Uveal Melanoma In Australia (1982–2014), Aaron B. Beasley, David B. Preen, Samuel Mclenachan, Elin S. Gray, Fred K. Chen

Research outputs 2014 to 2021

Aims:

We aimed to estimate the incidence and mortality of uveal melanoma (UM) in Australia from 1982 to 2014.

Methods:

Deidentified unit data for all cases of ocular melanoma were extracted from the Australian Cancer Database from 1 January 1982 to 31 December 2014. UM cases were extracted and trends in incidence and disease-specific mortality were calculated. Incidence rates were age-standardised against the 2001 Australian Standard Population. Mortality was assessed using Cox regression.

Results:

From 1982 to 2014, there were 5087 cases of ocular melanoma in Australia, of which 4617 were classified as UM. The average age-standardised incidence rate of …