Medicine and Health Sciences Commons^™

Second Virtual International Symposium On Cellular And Organismal Stress Responses, September 8-9, 2022, Patricija Van Oosten-Hawle, Sarah J Backe, Anat Ben-Zvi, Dimitra Bourboulia, Mara Brancaccio, Jeff Brodsky, Melody Clark, Giorgio Colombo, Marc B Cox, Paolo De Los Rios, Frank Echtenkamp, Adrienne Edkins, Brian Freeman, Pierre Goloubinoff, Walid Houry, Jill Johnson, Paul Lapointe, Wei Li, Valerie Mezger, Len Neckers, Nadinath B Nillegoda, Veena Prahlad, Adam Reitzel, Ruth Scherz-Shouval, Lea Sistonen, Francis T F Tsai, Mark R Woodford, Mehdi Mollapour, Andrew W Truman

Faculty, Staff and Students Publications

The Second International Symposium on Cellular and Organismal Stress Responses took place virtually on September 8-9, 2022. This meeting was supported by the Cell Stress Society International (CSSI) and organized by Patricija Van Oosten-Hawle and Andrew Truman (University of North Carolina at Charlotte, USA) and Mehdi Mollapour (SUNY Upstate Medical University, USA). The goal of this symposium was to continue the theme from the initial meeting in 2020 by providing a platform for established researchers, new investigators, postdoctoral fellows, and students to present and exchange ideas on various topics on cellular stress and chaperones. We will summarize the highlights of …

International Collaboration On Palliative Care Development Between Asco And The Land Of Hornbills., Yin Yee Wong, Aaron Zi Jian Chiew, Vanessa Eaton, Frank D Ferris, Megan Kremzier, Boon Leong Lim, Winnie Hui Yee Ling, Asri Said, Vanessa Sarchet, Tung Hui Tiong, Pei Jye Voon, Yoke Ling Choo

Oncology Articles

PURPOSE: Palliative care in Sarawak is mainly provided by health care professionals with limited formal training in palliative care. Therefore, in 2020, collaborative work between Sarawak General Hospital, University Malaysia Sarawak, and ASCO began. This study reports on the outcome of this collaboration.

METHODS: The collaboration was initiated with the first ASCO Palliative Care e-course, Train the Trainer program, International Development and Education Award-Palliative Care and translation of ASCO Palliative Care Interdisciplinary Curriculum resources.

RESULTS: This collaboration has resulted in the change of practice of palliative care among the oncology team of Sarawak General Hospital.

CONCLUSION: It encourages more timely …

Editorial: Metabolic Regulation Under Oxidative Stress In Cancer, Elavarasan Subramani, Abishai Dominic, Pratip K Bhattacharya, Daniel E Frigo, Ilya Bederman, Ali Vaziri-Gohar

Faculty, Staff and Student Publications

Oxidative stress has emerged as a key component of cancer metabolism that impacts multiple facets of tumor biology (1). Recent studies have shed light on the complex interplay of cellular redox and its impact on molecular mechanisms that govern metabolic reprogramming under oxidative stress (2, 3). It is well established that altered glucose metabolism exhibited by tumor cells leads to an enormous oxidative burden through various metabolic routes (4, 5). What is less known but remains a great interest to the field is whether elevated oxidative stress has a causal role in …

Development And Internal Validation Of A Novel Nomogram For Predicting Lymph Node Invasion For Prostate Cancer Patients Undergoing Extended Pelvic Lymph Node Dissection, Zhen Li, Yixin Huang, Diwei Zhao, Xin Luo, Zeshen Wu, Xinyi Zheng, Ye Xie, Yixuan Liu, Jianwei Wu, Yulu Peng, Yonghong Li, Fangjian Zhou

Faculty, Staff and Student Publications

BACKGROUND: Few studies have focused on the performance of Briganti 2012, Briganti 2017 and MSKCC nomograms in the Chinese population in assessing the risk of lymph node invasion(LNI) in prostate cancer(PCa) patients and identifying patients suitable for extended pelvic lymph node dissection(ePLND). We aimed to develop and validate a novel nomogram based on Chinese PCa patients treated with radical prostatectomy(RP) and ePLND for predicting LNI.

METHODS: We retrospectively retrieved clinical data of 631 patients with localized PCa receiving RP and ePLND at a Chinese single tertiary referral center. All patients had detailed biopsy information from experienced uropathologist. Multivariate logistic-regression analyses …

Head And Neck Cancer Online Support Groups: Disparities In Participation And Impact On Patients, Benjamin Tam, Matthew Lin, Carlos Castellanos, Ruben Ulloa, Niels Kokot, Kevin Hur

Faculty, Staff and Student Publications

OBJECTIVE: To characterize the users of the head and neck cancer (HNC) online support group (OSG) and describe the perceived benefits of membership.

STUDY DESIGN: Cross-sectional.

SETTING: Online.

METHODS: An administered survey with questions asking about demographics, cancer history, treatment choices, and feelings about OSGs was posted on the 5 largest HNC OSGs on Facebook.

RESULTS: A total of 97 participants completed the survey. Mean age was 57.8 years old (standard deviation = 10.7 years). Most participants were female (50.5%) and Caucasian (92.8%). This cohort was well educated with 65.5% holding at least a college degree. Annual income was high …

Molecular Mechanisms Of Osteosarcoma Metastasis And Possible Treatment Opportunities, Xinhui Du, Hua Wei, Boya Zhang, Bangmin Wang, Zhehuang Li, Lon Kai Pang, Ruiying Zhao, Weitao Yao

Faculty, Staff and Student Publications

In osteosarcoma patients, metastasis of the primary cancer is the leading cause of death. At present, management options to prevent metastasis are limited and non-curative. In this study, we review the current state of knowledge on the molecular mechanisms of metastasis and discuss promising new therapies to combat osteosarcoma metastasis. Genomic and epigenomic changes, metabolic reprogramming, transcription factors, dysregulation of physiologic pathways, and alterations to the tumor microenvironment are some of the changes reportedly involved in the regulation of osteosarcoma metastasis. Key factors within the tumor microenvironment include infiltrating lymphocytes, macrophages, cancer-associated fibroblasts, platelets, and extracellular components such as vesicles, …

Unveiling The Prognostic Implications Of Rplp1 Upregulation In Osteosarcoma, Xinhui Du, Hua Wei, Boya Zhang, Lon Kai Pang, Ruiying Zhao, Xu Dong Zhang, Weitao Yao

Faculty, Staff and Student Publications

Osteosarcoma, a malignant bone tumor characterized by a high rate of metastasis and poor survival, presents a critical need for identifying novel biomarkers associated with metastasis. In this study, we conducted an extensive analysis utilizing transcriptional and clinical data sourced from databases such as GEO, TCGA, CCLE, R2, and Xena. And we discovered that Ribosomal protein LP1 (RPLP1) ranked among the top upregulated genes in relation to osteosarcoma metastasis. Notably, RPLP1 exhibited significant expression in both osteosarcoma cell lines and patient samples. Moreover, multiple osteosarcoma studies revealed a strong correlation between RPLP1 overexpression and worse metastasis-free survival as well as …

Lung Cancer In The Emergency Department, Jeremy R Walder, Saadia A Faiz, Marcelo Sandoval

Faculty, Staff and Student Publications

Background: Though decreasing in incidence and mortality in the USA, lung cancer remains the deadliest of all cancers. For a significant number of patients, the emergency department (ED) provides the first pivotal step in lung cancer prevention, diagnosis, and management. As screening recommendations and treatments advance, ED providers must stay up-to-date with the latest lung cancer recommendations. The purpose of this review is to identify the many ways that emergency providers may intersect with the disease spectrum of lung cancer and provide an updated array of knowledge regarding detection, management, complications, and interdisciplinary care.

Findings: Lung cancer, encompassing 10-12% of …

Dual Enhancement In The Radiosensitivity Of Prostate Cancer Through Nanoparticles And Chemotherapeutics, Nolan Jackson, Iona Hill, Abdulaziz Alhussan, Kyle Bromma, Jessica Morgan, Belal Abousaida, Yasmin Zahra, Yuri Mackeyev, Wayne Beckham, Steven Herchko, Sunil Krishnan, Devika Basnagge Chithrani

Faculty, Staff and Student Publications

BACKGROUND: Radiotherapy (RT) is an essential component in the treatment regimens for many cancer patients. However, the dose escalation required to improve curative results is hindered due to the normal tissue toxicity that is induced. The introduction of radiosensitizers to RT treatment is an avenue that is currently being explored to overcome this issue. By introducing radiosensitizers into tumor sites, it is possible to preferentially enhance the local dose deposited. Gold nanoparticles (GNPs) are a potential candidate that have shown great promise in increasing the radiosensitivity of cancer cells through an enhancement in DNA damage. Furthermore, docetaxel (DTX) is a …

Radiolabeled Nanomaterial For Cancer Diagnostics And Therapeutics: Principles And Concepts, Muskan Goel, Yuri Mackeyev, Sunil Krishnan

Faculty, Staff and Student Publications

In the last three decades, radiopharmaceuticals have proven their effectiveness for cancer diagnosis and therapy. In parallel, the advances in nanotechnology have fueled a plethora of applications in biology and medicine. A convergence of these disciplines has emerged more recently with the advent of nanotechnology-aided radiopharmaceuticals. Capitalizing on the unique physical and functional properties of nanoparticles, radiolabeled nanomaterials or nano-radiopharmaceuticals have the potential to enhance imaging and therapy of human diseases. This article provides an overview of various radionuclides used in diagnostic, therapeutic, and theranostic applications, radionuclide production through different techniques, conventional radionuclide delivery systems, and advancements in the delivery …

Proton Therapy With Concurrent Chemotherapy For Thoracic Esophageal Cancer: Toxicity, Disease Control, And Survival Outcomes, Michael S Rutenberg, Bradford S Hoppe, Jason S Starr, Ziad Awad, Mathew Thomas, Christopher G Morris, Perry Johnson, Randal H Henderson, Jeremy C Jones, Bharatsinh Gharia, Steven Bowers, Herbert C Wolfsen, Sunil Krishnan, Stephen J Ko, Hani M Babiker, Romaine C Nichols

Faculty, Staff and Student Publications

PURPOSE: When treating esophageal cancer with radiation therapy, it is critical to limit the dose to surrounding structures, such as the lung and/or heart, as much as possible. Proton radiation therapy allows a reduced radiation dose to both the heart and lungs, potentially reducing the risk of cardiopulmonary toxicity. Here, we report disease control, survival, and toxicity outcomes among patients with esophageal cancer treated with proton radiation therapy and concurrent chemotherapy (chemoradiation therapy; CRT) with or without surgery.

MATERIALS AND METHODS: We enrolled 17 patients with thoracic esophageal carcinoma on a prospective registry between 2010 and 2021. Patients received proton …

Novel Therapeutic Approaches To Treat Brain Cancer Combining 3d Cell Culture Models, Cold Atmospheric Plasma And Airborne Acoustic, Janith Wanigasekara

Doctoral

Glioblastoma (GBM), an adult-type diffuse grade 4 glioma (IDH wild type), is the most prevalent, aggressive, fatal, highly vascularized, malignant primary brain tumour in adults with a poor prognosis. Despite existing therapies such as surgical resection, radiation therapy and chemotherapy such as temozolomide (TMZ), patient survival remains largely unchanged over the last three decades. There is an urgent need for novel and effective therapeutic strategies that can overcome drug resistance, cross the blood brain barrier, and minimise off-target side effects that can negatively impact a patient's quality of life. The high failure rate of clinical trials is due to inefficient …

Incidental Detection Of A Rare Pediatric High-Grade Fibrosarcoma In A Post-Traumatic Setting: The Conundrum Of Intra-Abdominal Hematoma Versus Neoplasia, Kamand Khalaj, Nikoo Fattahi, Allen C Omo-Ogboi, Jaiyeola O Thomas-Ogunniyi, Olanrewaju A Ogunleye, Ashish Khanal, Larry A Kramer

Faculty, Staff and Student Publications

Infantile fibrosarcoma (IF) is a rare malignant fibroblastic tumor that affects infants and young children, occurring most commonly in the extremities. Here, we present a 14-year-old patient with an abdominal mass incidentally detected after a blunt injury to the abdomen. The initial trauma protocol CT revealed a high attenuation mesenteric lesion in the left central abdomen suggestive of mesenteric hematoma. However, the possibility of a solid neoplastic mass lesion could not be excluded. Further evaluation with dynamic contrast-enhanced serial MRI showed a progressive enhancing mass and excluded a hyperacute hematoma with active bleeding. The mass was resected, and histopathological examination …

Pten In Triple-Negative Breast Carcinoma: Protein Expression And Genomic Alteration In Pretreatment And Posttreatment Specimens, Hui Chen, Qingqing Ding, Laila Khazai, Li Zhao, Senthil Damodaran, Jennifer K Litton, Gaiane M Rauch, Clinton Yam, Jeffrey T Chang, Sahil Seth, Bora Lim, Alastair M Thompson, Elizabeth A Mittendorf, Beatriz Adrada, Kiran Virani, Jason B White, Elizabeth Ravenberg, Xingzhi Song, Rosalind Candelaria, Banu Arun, Naoto T Ueno, Lumarie Santiago, Sadia Saleem, Sausan Abouharb, Rashmi K Murthy, Nuhad Ibrahim, Mark J Routbort, Aysegul Sahin, Vicente Valero, William Fraser Symmans, Debu Tripathy, Wei-Lien Wang, Stacy Moulder, Lei Huo

Faculty, Staff and Student Publications

BACKGROUND: Recent advances have been made in targeting the phosphoinositide 3-kinase pathway in breast cancer. Phosphatase and tensin homolog (PTEN) is a key component of that pathway.

OBJECTIVE: To understand the changes in PTEN expression over the course of the disease in patients with triple-negative breast cancer (TNBC) and whether

METHODS: We compared PTEN expression by IHC between pretreatment tumors and residual tumors in the breast and lymph nodes after neoadjuvant chemotherapy in 96 patients enrolled in a TNBC clinical trial. A correlative analysis between PTEN protein expression and

RESULTS: With a stringent cutoff for PTEN IHC scoring, PTEN expression …

A Novel Case Of Eus-Guided Targeted Radiofrequency Ablation Of Metastatic Duodenal Renal Cell Carcinoma, Muhammad Vohra, Hemant Goyal, Putao Cen, Mairin Joseph-Talreja, Nirav Thosani

Faculty, Staff and Student Publications

No abstract provided.

One Patient With 4 Different Primary Cancers: A Case Report, Dung Thi Nguyen, Lan Mai Nguyen, Thang Le Phan, Quang Vinh Bui

Faculty, Staff and Student Publications

BACKGROUND: The development of medicine, especially in oncology, has been helping prolong the cancer patients' survival, but also leads to increasing the possibility of getting multiple cancers. However, the possibility of getting 4 primary cancers in 4 different sites is extremely rare.

CASE PRESENTATION: A 63-year-old female patient was diagnosed with thyroid cancer in 2018, and then with right colon cancer in 2019. In 2020, this patient was diagnosed with left renal pelvis cancer, and most recently, in April 2022, she was hospitalized with bladder cancer diagnosis. Thanks to being closely and regularly followed-up, her malignancies had been detected early …

5-Aminolevulinic Acid, Fluorescein Sodium, And Indocyanine Green For Glioma Margin Detection: Analysis Of Operating Wide-Field And Confocal Microscopy In Glioma Models Of Various Grades, Evgenii Belykh, Liudmila Bardonova, Irakliy Abramov, Vadim A Byvaltsev, Talgat Kerymbayev, Kwanha Yu, Debbie R Healey, Ernesto Luna-Melendez, Benjamin Deneen, Shwetal Mehta, James K Liu, Mark C Preul

Faculty, Staff and Students Publications

INTRODUCTION: Surgical resection remains the first-line treatment for gliomas. Several fluorescent dyes are currently in use to augment intraoperative tumor visualization, but information on their comparative effectiveness is lacking. We performed systematic assessment of fluorescein sodium (FNa), 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), and indocyanine green (ICG) fluorescence in various glioma models using advanced fluorescence imaging techniques.

METHODS: Four glioma models were used: GL261 (high-grade model), GB3 (low-grade model), and an

RESULTS: Our systematic analysis showed that wide-field imaging of highly malignant gliomas is equally efficient with 5-ALA, FNa, and ICG, although FNa is associated with more false-positive staining of …

Lox Upregulates Fak Phosphorylation To Promote Metastasis In Osteosarcoma, Xiang Chen, Margaret Clement, M John Hicks, Poonam Sarkar, M Waleed Gaber, Tsz-Kwong Man

Faculty, Staff and Students Publications

Osteosarcoma is a malignant bone tumor that commonly occurs in the pediatric population. Despite the use of chemotherapy and surgery, metastasis remains to be the leading cause of death in patients with osteosarcoma. We have previously reported that cytoplasmic mislocalization of p27 is associated with a poor outcome in osteosarcoma. In this study, we further show that lysyl oxidase (LOX) expression was associated with p27 mislocalization. LOX is an enigmatic molecule that acts as a tumor suppressor or a metastatic promoter; however, its role in osteosarcoma is still unclear. Hence, we performed both

Systemic Treatment Of Advanced And Metastatic Urothelial Cancer: The Landscape In Australia, Howard Gurney, Timothy D. Clay, Niara Oliveira, Shirley Wong, Ben Tran, Carole Harris

Research outputs 2022 to 2026

The 5-year survival rate of metastatic urothelial carcinoma (mUC) is estimated to be as low as 5%. Currently, systemic platinum-based chemotherapy followed by avelumab maintenance therapy is the only first-line treatment for mUC that has an overall survival benefit. Cisplatin-based chemotherapy (usually in combination with gemcitabine) is the preferred treatment but carboplatin is substituted where contraindications to cisplatin exist. Treatment with immune checkpoint inhibitors, antibody-drug conjugates, and kinase inhibitors has not yet demonstrated superiority to chemotherapy as first-line therapy and remains investigational in this setting. A recent media release indicates that chemotherapy plus nivolumab gives an OS advantage as first-line …

Investigation Of The Dyrk1a Regulation By Lzts2-Sipa1l1 Complex, Rebecca Gunnin, Austin Witt B.S., Larisa Litovchick M.D.,Ph.D.

UROP Posters

A region on chromosome 21, the Down Syndrome critical region (DSCR), is associated with major defects found in Down Syndrome, such as craniofacial malformations. DYRK1A is a gene found on chromosome 21 within the DSCR that encodes an enzyme, dual specificity tyrosine-phosphorylation-regulated kinase 1A. DYRK1A is known to phosphorylate many substrate proteins and is thought to be involved in tumor suppression, neurological development, cell cycle regulation, and aging. Recently, the Litovchick lab and others reported that DYRK1A also plays a role in the double-strand break repair of DNA, which could lead to mutations and tumorigenesis, if deregulated.

The Litovchick lab …

Early Detection Of Mandible Osteoradionecrosis Risk In A High Comorbidity Veteran Population, David Chamberlayne Wilde, Sagar Kansara, Logan Banner, Rickey Morlen, David Hernandez, Andrew Tsao Huang, Weiyuan Mai, Clifton David Fuller, Stephen Lai, Vlad Constantin Sandulache

Faculty, Staff and Student Publications

OBJECTIVE: Osteoradionecrosis (ORN) of the mandible is a devastating complication of external beam radiation therapy (EBRT) for head and neck squamous cell carcinoma (HNSCC). We sought to ascertain ORN risk in a Veteran HNSCC population treatment with definitive or adjuvant EBRT and followed prospectively.

STUDY DESIGN: Retrospective analysis of prospective cohort.

SETTING: Tertiary care Veterans Health Administration (VHA) medical center.

METHODS: Patients with HNSCC who initiated treatment at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) are prospectively tracked for quality of care purposes through the end of the cancer surveillance period (5 years post treatment completion). We retrospectively …

Policy Options To Facilitate Cancer Genomic Variant Data Sharing: Outcomes Of A Modified Policy Delphi, Jill O Robinson, Amira Daoud, Janis Geary, Vasiliki Rahimzadeh, Juli Bollinger, Christi J Guerrini, Robert Cook-Deegan, Amy L Mcguire, Mary A Majumder

Center for Medical Ethics and Health Policy Staff Publications

Sharing cancer gene variant and relevant clinical data could accelerate progress in cancer genomics. However, data sharing is currently impeded by issues related to financial sustainability, equity, incentives, privacy and security, and data quality. Evidence-based policy options to facilitate data sharing in these domains, and ultimately improve interpretation of cancer-associated genomic variants, are therefore needed. We conducted a modified policy Delphi with expert stakeholders that involved generating, evaluating, and ranking potential policy options to address these issues, with a focus on the US context. We found policy options in the financial sustainability domain were highly ranked, particularly stable funding for …

Targeting Nuclear Hormone Receptors For The Prevention Of Breast Cancer, Cassandra L Moyer, Powel H Brown

Faculty, Staff and Student Publications

Advancements in research have led to the steady decline of breast cancer mortality over the past thirty years. However, breast cancer incidence has continued to rise, resulting in an undue burden on healthcare costs and highlighting a great need for more effective breast cancer prevention strategies, including targeted chemo preventative agents. Efforts to understand the etiology of breast cancer have uncovered important roles for nuclear receptors in the development and progression of breast cancer. Targeted therapies to inhibit estrogen receptor (ER) and progesterone receptor (PR) signaling (selective ER modulators, aromatase inhibitors and selective PR modulators) have shown great promise for …

Neuroanatomical Correlates Of The Late Positive Potential In Youth With Pediatric Bipolar Disorder, Alessio Simonetti, Marijn Lijffijt, Sherin Kurian, Johanna Saxena, Delfina Janiri, Marianna Mazza, Giulio Carriero, Lorenzo Moccia, Benson Mwangi, Alan C Swann, Jair C Soares

Faculty, Staff and Student Publications

BACKGROUND: The late positive potential (LPP) could be a marker of emotion dysregulation in youth with pediatric bipolar disorder (PBD). However, the neuroanatomical correlates of the LPP are still not clarified.

OBJECTIVE: To provide cortical and deep gray matter correlates of the LPP in youth, specifically, youth with PBD.

METHODS: Twenty-four 7 to 17 years-old children with PBD and 28 healthy controls (HC) underwent cortical thickness and deep gray matter volumes measurements through magnetic resonance imaging and LPP measurement elicited by passively viewing emotional faces through electroencephalography. T-tests compared group differences in LPP, cortical thickness, and deep gray matter volumes. …

Development Of A Clinical Prediction Model For Diabetes In Chronic Pancreatitis: The Predict3c Study, Christie Jeon, Phil A Hart, Liang Li, Yunlong Yang, Eleanor Chang, Melena D Bellin, William E Fisher, Evan L Fogel, Christopher E Forsmark, Walter G Park, Stephen K Van Den Eeden, Santhi Swaroop Vege, Jose Serrano, David C Whitcomb, Dana K Andersen, Darwin L Conwell, Dhiraj Yadav, Mark O Goodarzi

Faculty, Staff and Student Publications

Objective: Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP.

Research design and methods: This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was …

Editorial: Advances In The Biological Effects Of Ionizing Radiation, Fada Guan, Lina Zhao, Julianna K Bronk, Mirjana Maletic-Savatic, David R Grosshans, David J Carlson

Faculty, Staff and Student Publications

No abstract provided.

Powerful, Scalable And Resource-Efficient Meta-Analysis Of Rare Variant Associations In Large Whole Genome Sequencing Studies, Xihao Li, Corbin Quick, Hufeng Zhou, Sheila M Gaynor, Yaowu Liu, Han Chen, Margaret Sunitha Selvaraj, Ryan Sun, Rounak Dey, Donna K Arnett, Lawrence F Bielak, Joshua C Bis, John Blangero, Eric Boerwinkle, Donald W Bowden, Jennifer A Brody, Brian E Cade, Adolfo Correa, L Adrienne Cupples, Joanne E Curran, Paul S De Vries, Ravindranath Duggirala, Barry I Freedman, Harald H H Göring, Xiuqing Guo, Jeffrey Haessler, Rita R Kalyani, Charles Kooperberg, Brian G Kral, Leslie A Lange, Ani Manichaikul, Lisa W Martin, Stephen T Mcgarvey, Braxton D Mitchell, May E Montasser, Alanna C Morrison, Take Naseri, Jeffrey R O'Connell, Nicholette D Palmer, Patricia A Peyser, Bruce M Psaty, Laura M Raffield, Susan Redline, Alexander P Reiner, Muagututi'a Sefuiva Reupena, Kenneth M Rice, Stephen S Rich, Colleen M Sitlani, Jennifer A Smith, Kent D Taylor, Ramachandran S Vasan, Cristen J Willer, James G Wilson, Lisa R Yanek, Wei Zhao, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Lipids Working Group, Jerome I Rotter, Pradeep Natarajan, Gina M Peloso, Zilin Li, Xihong Lin

Faculty, Staff and Student Publications

Meta-analysis of whole genome sequencing/whole exome sequencing (WGS/WES) studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with complex phenotypes. Existing rare variant meta-analysis approaches are not scalable to biobank-scale WGS data. Here we present MetaSTAAR, a powerful and resource-efficient rare variant meta-analysis framework for large-scale WGS/WES studies. MetaSTAAR accounts for relatedness and population structure, can analyze both quantitative and dichotomous traits and boosts the power of rare variant tests by incorporating multiple variant functional annotations. Through meta-analysis of four lipid traits in 30,138 ancestrally diverse samples from 14 studies of …

Payer Reimbursement Practices And Incentives For Improving Interpretation Of Germline Genetic Testing, Patricia Deverka, Janis Geary, Charles Mathews, Matan Cohen, Gillian Hooker, Mary Majumder, Zuzana Skvarkova, Robert Cook-Deegan

Center for Medical Ethics and Health Policy Staff Publications

Germline genetic testing for inherited cancer risk has shifted to multi-gene panel tests (MGPTs). While MGPTs detect more pathogenic variants, they also detect more variants of uncertain significance (VUSs) that increase the possibility of harms such as unnecessary surgery. Data sharing by laboratories is critical to addressing the VUS problem. However, barriers to sharing and an absence of incentives have limited laboratory contributions to the ClinVar database. Payers can play a crucial role in the expansion of knowledge and effectiveness of genetic testing. Current policies affecting MGPT reimbursement are complex and create perverse incentives. Trends in utilization and coverage for …

Association Of Hearing Loss And Tinnitus Symptoms With Health-Related Quality Of Life Among Long-Term Oropharyngeal Cancer Survivors, Puja Aggarwal, Marc-Elie Nader, Paul W Gidley, Raj Pratihar, Shirin Jivani, Adam S Garden, Frank E Mott, Ryan P Goepfert, Christopher Wallace Ogboe, Camille Charles, Clifton D Fuller, Stephen Y Lai, G Brandon Gunn, Erich M Sturgis, Ehab Y Hanna, Katherine A Hutcheson, Sanjay Shete

Faculty, Staff and Student Publications

BACKGROUND: This study investigated the association of hearing loss and tinnitus with overall health-related quality of life (HRQoL) among long-term oropharyngeal cancer (OPC) survivors.

METHODS: This study included OPC survivors treated between 2000 and 2013 and surveyed from September 2015 to July 2016. Hearing loss and tinnitus were measured by asking survivors to rate their "difficulty with hearing loss and/or ringing in the ears" from 0 (not present) to 10 (as bad as you can imagine). Hearing loss and tinnitus scores were categorized as follows: 0 for none, 1-4 for mild, and 5-10 for moderate to severe. The primary outcome …

Tanshinone Iia Inhibits Cell Viability And Promotes Puma-Mediated Apoptosis Of Oral Squamous Cell Carcinoma, Shuangze Han, Xinfang Yu, Ruirui Wang, Xiaocong Wang, Lulu Liu, Qing Zhao, Rongbo Xie, Ming Li, Zhong Su Zhou

Faculty, Staff and Students Publications

Apoptosis alteration is responsible for tumorigenesis and tumor resistance to therapies. The natural product Tanshinone IIA (Tan IIA) exhibits potent inhibitory effects against various tumors. However, the effect of Tan IIA on apoptosis and its underlying mechanism remains elusive in oral squamous cell carcinoma (OSCC). Here, we demonstrated that Tan IIA dose-dependently suppressed cell viability and colony formation in CAL27, SCC4, and SCC25 cells. Moreover, Tan IIA inhibited Akt activation from inducing Foxo3a dephosphorylation and PUMA-mediated apoptosis. PUMA or Foxo3a knockdown compromised the inhibitory effect of Tan IIA on OSCC cells. Tan IIA administration inhibited CAL27-deprived xenograft tumor growth and …