Medicine and Health Sciences Commons^™

Subendocardial And Transmural Myocardial Ischemia: Clinical Characteristics, Prevalence, And Outcomes With And Without Revascularization, K Lance Gould, Tung Nguyen, Richard Kirkeeide, Amanda E Roby, Linh Bui, Danai Kitkungvan, Monica B Patel, Mohammad Madjid, Mary Haynie, Dejian Lai, Ruosha Li, Jagat Narula, Nils P Johnson

Faculty, Staff and Student Publications

BACKGROUND: Subendocardial ischemia is commonly diagnosed but not quantified by imaging.

OBJECTIVES: This study sought to define size and severity of subendocardial and transmural stress perfusion deficits, clinical associations, and outcomes.

METHODS: Regional rest-stress perfusion in mL/min/g, coronary flow reserve, coronary flow capacity (CFC), relative stress flow, subendocardial stress-to-rest ratio and stress subendocardial-to-subepicardial ratio as percentage of left ventricle were measured by positron emission tomography (PET) with rubidium Rb 82 and dipyridamole stress in serial 6,331 diagnostic PETs with prospective 10-year follow-up for major adverse cardiac events with and without revascularization.

RESULTS: Of 6,331 diagnostic PETs, 1,316 (20.7%) had severely …

Sociodemographic Differences In Menthol Cigarette Use In The United States, Rajesh Talluri, Sanjay Shete

Faculty, Staff and Student Publications

Background: Menthol cigarette use is associated with higher smoking initiation and reduced smoking cessation. We investigated sociodemographic differences in menthol and nonmenthol cigarette use in the United States.

Methods: We used the most recent available data from the May 2019 wave of the nationally-representative Tobacco Use Supplement to the Current Population Survey. The survey weights were used to estimate the national prevalence of individuals who currently smoke among individuals who use menthol and nonmenthol cigarettes. Survey-weighted logistic regression methods were used to estimate the association of menthol cigarette use with formerly smoking cigarettes and attempting to quit within the past …

Positron Emission Tomography Derived Metrics In Relapsed Or Refractory Large B-Cell Lymphoma With Residual Disease Before Autologous Stem Cell Transplant, Hua-Jay J Cherng, Guofan Xu, Lei Feng, Raphael Steiner, Luis Fayad, Paolo Strati, Ranjit Nair, Loretta J Nastoupil, Hun Ju Lee, Sattva S Neelapu, Christopher R Flowers, Maria Rodriguez, Michael Wang, Fredrick Hagemeister, Chelsea C Pinnix, Jeremy Ramdial, Samer Srour, Yago Nieto, Katayoun Rezvani, Richard Champlin, Partow Kebriaei, Jason Westin, Homer A Macapinlac, Elizabeth Shpall, Sairah Ahmed

Faculty, Staff and Student Publications

Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative treatment for patients with relapsed or refractory large B-cell lymphoma (rrLBCL) with chemosensitive disease. A18 F-fluorodeoxyglucose positron emission tomography (PET) scan after salvage chemotherapy is used to assess response and eligibility for ASCT, but metrics for chemosensitivity in patients with residual disease are not well defined. We performed a single-centre retrospective analysis of 92 patients with a partial response or stable disease after salvage chemotherapy for rrLBCL who received ASCT to investigate PET-derived parameters and their prognostic utility. The Deauville 5-point Scale (D-5PS) score, …

Impact Of Region-Of-Interest Size On Immune Profiling Using Multiplex Immunofluorescence Tyramide Signal Amplification For Paraffin-Embedded Tumor Tissues, Baohua Sun, Caddie Laberiano-Fernández, Ruth Salazar-Alejo, Jiexin Zhang, Jose Luis Solorzano Rendon, Jack Lee, Luisa Maren Solis Soto, Ignacio Ivan Wistuba, Edwin Roger Parra

Faculty, Staff and Student Publications

Introduction: Representative regions of interest (ROIs) analysis from the whole slide images (WSI) are currently being used to study immune markers by multiplex immunofluorescence (mIF) and single immunohistochemistry (IHC). However, the amount of area needed to be analyzed to be representative of the entire tumor in a WSI has not been defined.

Methods: We labeled tumor-associated immune cells by mIF and single IHC in separate cohorts of non-small cell lung cancer (NSCLC) samples and we analyzed them as whole tumor area as well as using different number of ROIs to know how much area will be need to represent the …

Association Of Cyclooxygenase-2 Expression With Endoplasmic Reticulum Stress And Autophagy In Triple-Negative Breast Cancer, Haechan Lee, Sungwook Jung, Gyungyub Gong, Bora Lim, Hee Jin Lee

Faculty, Staff and Student Publications

Cyclooxygenase-2 plays a role in oncogenesis and its overexpression is associated with triple-negative breast cancer. However, the mechanisms whereby cyclooxygenase-2 contribute to breast cancer are complex and not well understood. Cyclooxygenase-2 overexpression causes hypoxia, oxidative stress, and endoplasmic reticulum stress. The aim of this study is to investigate the correlations among cyclooxygenase-2 expression, endoplasmic reticulum stress-associated molecules, and autophagy-associated molecules in triple-negative breast cancer. Surgical specimens from two cohorts of triple-negative breast cancer patients without neoadjuvant systemic therapy were analyzed: cohorts 1 and 2 consisted of 218 cases from 2004 to 2006 and 221 cases from 2007 to 2009, respectively. …

Improved Outcomes With “7+3” Induction Chemotherapy For Acute Myeloid Leukemia Over The Past Four Decades: Analysis Of Swog Trial Data, Megan Othus, Guillermo Garcia-Manero, John E Godwin, James K Weick, Frederick R Appelbaum, Harry P Erba, Elihu H Estey

Faculty, Staff and Student Publications

We have previously shown that complete response (CR) rates and overall survival of patients with acute myeloid leukemia have improved since the 1980s. However, we have not previously evaluated how the length of first CR (CR1) has changed over this time period. To address this, we analyzed 1,247 patients aged 65 or younger randomized to "7+3" arms from five SWOG studies: S8600 (n=530), S9031 (n=98), S9333 (n=57), S0106 (n=301), and S1203 (n=261). We evaluated length of CR1 and survival after relapse from CR1 over the four decades that these studies represent. Both length of CR1 and survival after relapse from …

Flecainide For Conversion And Maintenance Of Sinus Rhythm After Mitral Valve Replacement In Rheumatic Atrial Fibrillation, Umesh Tripathi, Aditya Kapoor, Surendra Kumar Agarwal, Prabhat Tewari, Shantanu Pande, Bipin Chandra, Ankit Sahu, Roopali Khanna, Sudeep Kumar, Naveen Garg, Satyendra Tewari

Faculty, Staff and Student Publications

BACKGROUND: Despite successful mitral valve replacement (MVR), many patients remain in AF. Flecainide can be useful in these patients but has not been used because of underlying structural heart disease.

METHODS: We assessed oral flecainide for conversion and maintenance of SR in 25 patients of chronic rheumatic AF following MVR (age 34.4 yrs, mean AF duration: 3.6 yrs). Non-converters underwent DC cardioversion at 24 h and 4 weeks. Patients received flecainide and bb/diltiazem at discharge.

RESULTS: Single oral dose of Flecainide achieved SR in 6/25 (24%) while 19/25 achieved SR after DCC; at24 h 21/25 (84%) were in SR. With …

Circadian Rhythms Of Risk Factors And Management In Atherosclerotic And Hypertensive Vascular Disease: Modern Chronobiological Perspectives Of An Ancient Disease, Yong-Jian Geng, Michael H Smolensky, Oliver Sum-Ping, Ramon Hermida, Richard J Castriotta

Faculty, Staff and Student Publications

Atherosclerosis, a chronic inflammatory disease of the arteries that appears to have been as prevalent in ancient as in modern civilizations, is predisposing to life-threatening and life-ending cardiac and vascular complications, such as myocardial and cerebral infarctions. The pathogenesis of atherosclerosis involves intima plaque buildup caused by vascular endothelial dysfunction, cholesterol deposition, smooth muscle proliferation, inflammatory cell infiltration and connective tissue accumulation. Hypertension is an independent and controllable risk factor for atherosclerotic cardiovascular disease (CVD). Conversely, atherosclerosis hardens the arterial wall and raises arterial blood pressure. Many CVD patients experience both atherosclerosis and hypertension and are prescribed medications to concurrently …

Fostering A High-Functioning Team In Cancer Care Using The 4r Oncology Model: Assessment In A Large Health System And A Blueprint For Other Institutions, Raymond Liu, Christine B Weldon, Elizabeth Linehan, Nancy Gordon, Thea Abbe, Marti Hennings, Henie James, Jed Katzel, Chun Ng, Megumi Tomita, Jeffrey B Velotta, Stephanie Ossowski, Lori C Sakoda, Sharon Likely Sprague, Anna Dowling, Kimberly Beringer, Arliene Ravelo, Elaine Yu, Julia R Trosman

Faculty, Staff and Student Publications

PURPOSE: Delivering cancer care by high-functioning multidisciplinary teams promises to address care fragmentation, which threatens care quality, affects patient outcomes, and strains the oncology workforce. We assessed whether the 4R Oncology model for team-based interdependent care delivery and patient self-management affected team functioning in a large community-based health system.

METHODS: 4R was deployed at four locations in breast and lung cancers and assessed along four characteristics of high-functioning teams: recognition as a team internally and externally; commitment to an explicit shared goal; enablement of interdependent work to achieve the goal; and engagement in regular reflection to adapt objectives and processes. …

Cardiovascular Disease Risk Factors Among Middle-Aged And Older Adult Vietnamese American Members Of A Northern California Health Plan, Donna B Haysbert, Joan C Lo, Nirmala D Ramalingam, Nancy P Gordon

Faculty, Staff and Student Publications

OBJECTIVE: There is increasing recognition that cardiovascular disease (CVD) risk factors vary by Asian subgroups. We examined CVD risk factor prevalence among Vietnamese adults in a northern California health plan.

METHODS: We used electronic health record data to examine smoking, overweight/obesity (body mass index ≥23.0 kg/m

RESULTS: Current smoking prevalence was 20.3% for middle-aged men, 7.0% for older men, and

CONCLUSIONS: Study results suggest that more research on health conditions, lifestyle, and social factors among Vietnamese American adults is needed to develop culturally competent interventions to reduce CVD risk in this growing ethnic group.

Examining Sociodemographic Correlates Of Opioid Use, Misuse, And Use Disorders In The All Of Us Research Program, Hsueh-Han Yeh, Cathryn Peltz-Rauchman, Christine C Johnson, Pamala A Pawloski, David Chesla, Stephen C Waring, Alan B Stevens, Mara Epstein, Christine Joseph, Lisa R Miller-Matero, Hongsheng Gui, Amy Tang, Eric Boerwinkle, Mine Cicek, Cheryl R Clark, Elizabeth Cohn, Kelly Gebo, Roxana Loperena, Kelsey Mayo, Stephen Mockrin, Lucila Ohno-Machado, Sheri Schully, Andrea H Ramirez, Jun Qian, Brian K Ahmedani

Faculty, Staff and Student Publications

Background: The All of Us Research Program enrolls diverse US participants which provide a unique opportunity to better understand the problem of opioid use. This study aims to estimate the prevalence of opioid use and its association with sociodemographic characteristics from survey data and electronic health record (EHR).

Methods: A total of 214,206 participants were included in this study who competed survey modules and shared EHR data. Adjusted logistic regressions were used to explore the associations between sociodemographic characteristics and opioid use.

Results: The lifetime prevalence of street opioids was 4%, and the nonmedical use of prescription opioids was 9%. …

Stellettin B Sensitizes Glioblastoma To Dna-Damaging Treatments By Suppressing Pi3k-Mediated Homologous Recombination Repair, Xin Peng, Shaolu Zhang, Yingying Wang, Zhicheng Zhou, Zixiang Yu, Zhenxing Zhong, Liang Zhang, Zhe-Sheng Chen, Francois X Claret, Moshe Elkabets, Feng Wang, Fan Sun, Ran Wang, Han Liang, Hou-Wen Lin, Dexin Kong

Faculty, Staff and Student Publications

Glioblastoma (GBM) is the most aggressive type of cancer. Its current first-line postsurgery regimens are radiotherapy and temozolomide (TMZ) chemotherapy, both of which are DNA damage-inducing therapies but show very limited efficacy and a high risk of resistance. There is an urgent need to develop novel agents to sensitize GBM to DNA-damaging treatments. Here it is found that the triterpene compound stellettin B (STELB) greatly enhances the sensitivity of GBM to ionizing radiation and TMZ in vitro and in vivo. Mechanistically, STELB inhibits the expression of homologous recombination repair (HR) factors BRCA1/2 and RAD51 by promoting the degradation of PI3Kα …

Mass Spectrometry Based Biomarkers For Early Detection Of Hcc Using A Glycoproteomic Approach, Yehia Mechref, Wenjing Peng, Sakshi Gautam, Parisa Ahmadi, Yu Lin, Jianhui Zhu, Jie Zhang, Suyu Liu, Amit G Singal, Neehar D Parikh, David M Lubman

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related mortality worldwide and 80%-90% of HCC develops in patients that have underlying cirrhosis. Better methods of surveillance are needed to increase early detection of HCC and the proportion of patients that can be offered curative therapies. Recent work in novel mass spec-based methods for glycomic and glycopeptide analysis for discovery and confirmation of markers for early detection of HCC versus cirrhosis is reviewed in this chapter. Results from recent work in these fields by several groups and the progress made in developing markers of early HCC which can outperform …

Risk Prediction Of Pancreatic Cancer In Patients With Recent-Onset Hyperglycemia: A Machine-Learning Approach, Wansu Chen, Rebecca K Butler, Eva Lustigova, Suresh T Chari, Anirban Maitra, Jo A Rinaudo, Bechien U Wu

Faculty, Staff and Student Publications

Background: New-onset diabetes (NOD) has been suggested as an early indicator of pancreatic cancer. However, the definition of NOD by the American Diabetes Association requires 2 simultaneous or consecutive elevated glycemic measures. We aimed to apply a machine-learning approach using electronic health records to predict the risk in patients with recent-onset hyperglycemia.

Materials and methods: In this retrospective cohort study, health plan enrollees 50 to 84 years of age who had an elevated (6.5%+) glycated hemoglobin (HbA1c) tested in January 2010 to September 2018 with recent-onset hyperglycemia were identified. A total of 102 potential predictors were extracted. Ten imputation datasets …

A Case Of Successful Treatment Of Recurrent Urinary Tract Infection By Extended-Spectrum Β-Lactamase Producing Klebsiella Pneumoniae Using Oral Lyophilized Fecal Microbiota Transplant, Naomi Bier, Blake Hanson, Zhi-Dong Jiang, Herbert L Dupont, Cesar A Arias, William R Miller

Faculty, Staff and Student Publications

Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae UTIs in a patient with an ileal conduit and urostomy. In the 18 months after FMT, the patient had not experienced new infections with ESBL-producing organisms. The urine and stool microbiomes of the patient were tracked before and post-FMT using 16s RNA sequencing with measurement of α-diversity. Sequencing of …

Editorial: The Interplay Between Microbiota And Allergen In Shaping Respiratory Mucosa Immunity: Role In Development Of Asthma, Zhenwei Xia, Wenwei Zhong, Min Wu, Scott E Evans

Faculty, Staff and Student Publications

No abstract provided.

Global Research Trends And Prospects Related To Tumor Microenvironment Within Triple Negative Breast Cancer: A Bibliometric Analysis, Peiting Li, Jun Li, Xiaofei Tong, Zhenyang Xiao, Wuliang Diao, Chi Zhong, Jianda Zhou, Wei Wu

Faculty, Staff and Student Publications

Background and aims: The tumor microenvironment (TME) has pivotal parts within multiple tumor models of onset/progression, such as triple-negative breast cancer (TNBC). This bibliometric analysis was developed to explore trends and research niches revolving around TME in TNBC.

Methods: Web of Science Core Collection was queried for identifying studies linked with TME in TNBC, after which the VOSviewer, CiteSpace, and R software programs were used to conduct bibliometric analyses and to generate corresponding visualizations.

Results: In total, this study included 1,604 studies published from 2005-2023. The USA and China exhibited the highest numbers of citations, and the research institutions with …

The Assembled Genome Of The Stroke-Prone Spontaneously Hypertensive Rat, Theodore S Kalbfleisch, Nahla A Hussien Abouel Ela, Kai Li, Wesley A Brashear, Kelli J Kochan, Andrew E Hillhouse, Yaming Zhu, Isha S Dhande, Eric J Kline, Elizabeth A Hudson, Terence D Murphy, Françoise Thibaud-Nissen, Melissa L Smith, Peter A Doris

Faculty, Staff and Student Publications

BACKGROUND: We report the creation and evaluation of a de novo assembly of the genome of the spontaneously hypertensive rat, the most widely used model of human cardiovascular disease.

METHODS: The genome is assembled from long read sequencing (PacBio HiFi and continuous long read data [CLR]) and scaffolded with long-range structural information obtained from Bionano optical maps and proximity ligation sequencing proximity analysis of the genome. The genome assembly was polished with Illumina short reads. Completeness of the assembly was investigated using Benchmarking Universal Single Copy Orthologs analysis. The genome assembly was also evaluated with the rat reference gene set, …

Frontostriatal And Limbic Contributions To Cognitive Decline In Parkinson’S Disease, Gregory Brown, Jonathan Hakun, Mechelle M Lewis, Sol De Jesus, Guangwei Du, Paul J Eslinger, Lan Kong, Xuemei Huang

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: The circuitry underlying heterogenous cognitive profiles in Parkinson's disease (PD) remains unclear. The purpose of this study is to investigate whether structural changes in frontostriatal and limbic pathways contribute to different cognitive trajectories in PD.

METHODS: We obtained clinical and multimodal MRI data from 120 control and 122 PD subjects without dementia or severe motor disability. T1/T2-weighted images estimated volume, and diffusion imaging evaluated fractional anisotropy (FA) of frontostriatal (striatum and frontostriatal white matter [FSWM]) and limbic (hippocampus and fornix) structures. Montreal Cognitive Assessment (MoCA) gauged total and domain-specific (attention/executive and memory) cognitive function. Linear mixed-effects models …

Molecular Predictors Of Immunophenotypic Measurable Residual Disease Clearance In Acute Myeloid Leukemia, Maximilian Stahl, Andriy Derkach, Noushin Farnoud, Jan Philipp Bewersdorf, Troy Robinson, Christopher Famulare, Christina Cho, Sean Devlin, Kamal Menghrajani, Minal A Patel, Sheng F Cai, Linde A Miles, Robert L Bowman, Mark B Geyer, Andrew Dunbar, Zachary D Epstein-Peterson, Erin Mcgovern, Jessica Schulman, Jacob L Glass, Justin Taylor, Aaron D Viny, Eytan M Stein, Bartlomiej Getta, Maria E Arcila, Qi Gao, Juliet Barker, Brian C Shaffer, Esperanza B Papadopoulos, Boglarka Gyurkocza, Miguel-Angel Perales, Omar Abdel-Wahab, Ross L Levine, Sergio A Giralt, Yanming Zhang, Wenbin Xiao, Nidhi Pai, Elli Papaemmanuil, Martin S Tallman, Mikhail Roshal, Aaron D Goldberg

Faculty, Staff and Student Publications

Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). However, pre-treatment molecular predictors of immunophenotypic MRD clearance remain unclear. We analyzed a dataset of 211 patients with pre-treatment next-generation sequencing who received induction chemotherapy and had MRD assessed by serial immunophenotypic monitoring after induction, subsequent therapy, and allogeneic stem cell transplant (allo-SCT). Induction chemotherapy led to MRD- remission, MRD+ remission, and persistent disease in 35%, 27%, and 38% of patients, respectively. With subsequent therapy, 34% of patients with MRD+ and 26% of patients with persistent disease converted to MRD-. Mutations in CEBPA, NRAS, KRAS, and …

Combining Mek And Src Inhibitors For Treatment Of Colorectal Cancer Demonstrate Increased Efficacy In Vitro But Not In Vivo, Fan Fan, Susmita Ghosh, Reid Powell, Jason Roszik, Yongsun Park, Mary Sobieski, Alexey Sorokin, Clifford Stephan, Scott Kopetz, Lee M Ellis, Rajat Bhattacharya

Faculty, Staff and Student Publications

Metastatic colorectal cancer (mCRC) is the second leading cause of cancer deaths in the United States. More than 50% of patients with mCRC harbor mutations of the oncogenic driver RAS (KRAS or NRAS). Because directly targeting most mutations of RAS is technically challenging, researchers have concentrated on targeting MEK, a downstream mediator of RAS. However, targeting MEK as single-agent therapy is ineffective in patients with mCRC. We hypothesize that combining a MEK inhibitor with other agents can enhance the efficacy of MEK targeting in mCRC. Unbiased high-throughput screening (HTS) was performed to identify drugs that enhance the efficacy of MEK …

Development And Validation Of Early Death Risk Score Model For Emergency Status Prediction In Very Severe Aplastic Anemia, Xu Liu, Wenrui Yang, Li Zhang, Liping Jing, Lei Ye, Kang Zhou, Yuan Li, Jianping Li, Huihui Fan, Yang Yang, Youzhen Xiong, Xin Zhao, Fengkui Zhang

Faculty, Staff and Student Publications

This study developed and validated the Early Death Risk Score Model for early identification of emergency patients with very severe aplastic anemia (VSAA). All 377 patients with VSAA receiving first-line immunosuppressive therapy (IST) were categorized into training (n=252) and validation (n=125) cohorts. In the training cohort, age >24 years, absolute neutrophil count ≤0.015×109/L, serum ferritin >900ng/mL and times of fever before IST >1 time were significantly associated with early death. Covariates were assigned scores and categorized as: low (score 0-4), medium (score 5-7) and high (score ≥8) risk. Early death rate was significantly different between risk groups and the validation …

Circulating Vitamin D And Breast Cancer Risk: An International Pooling Project Of 17 Cohorts, Kala Visvanathan, Alison M Mondul, Anne Zeleniuch-Jacquotte, Molin Wang, Mitchell H Gail, Shiaw-Shyuan Yaun, Stephanie J Weinstein, Marjorie L Mccullough, A Heather Eliassen, Nancy R Cook, Claudia Agnoli, Martin Almquist, Amanda Black, Julie E Buring, Chu Chen, Yu Chen, Tess Clendenen, Laure Dossus, Veronika Fedirko, Gretchen L Gierach, Edward L Giovannucci, Gary E Goodman, Marc T Goodman, Pascal Guénel, Göran Hallmans, Susan E Hankinson, Ronald L Horst, Tao Hou, Wen-Yi Huang, Michael E Jones, Corrine E Joshu, Rudolf Kaaks, Vittorio Krogh, Tilman Kühn, Marina Kvaskoff, I-Min Lee, Yahya Mahamat-Saleh, Johan Malm, Jonas Manjer, Gertraud Maskarinec, Amy E Millen, Toqir K Mukhtar, Marian L Neuhouser, Trude E Robsahm, Minouk J Schoemaker, Sabina Sieri, Malin Sund, Anthony J Swerdlow, Cynthia A Thomson, Giske Ursin, Jean Wactawski-Wende, Ying Wang, Lynne R Wilkens, Yujie Wu, Emilie Zoltick, Walter C Willett, Stephanie A Smith-Warner, Regina G Ziegler

Faculty, Staff and Student Publications

Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42-68) years at blood collection and 63 (49-75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, …

Pseudohypoadrenalism, A Subclinical Cortisol Metabolism Disorder In Hyperuricemia, Ruixia Bao, Beibei Chen, Jujie Pan, Alexander Wang, Haiyang Yu, Qian Chen, Yi Zhang, Tao Wang

Faculty, Staff and Student Publications

Background: Hyperuricemia is a known risk factor of lipid metabolism disorder. However, the mechanisms have not been fully understood.

Methods: The serum samples from hyperuricemia subjects were used to analyze the correlation between serum uric acid and clinical characteristics. Hyperuricemia mice induced by potassium oxonate (PO) and adenine were used to explore glucocorticoid metabolism.

Results: In hyperuricemia patients, the levels of serum uric acid were positively correlated with the levels of γ-glutamyltransferase, associated with a cortisol metabolism disorder. In hyperuricemia state, the adrenal glands failed to respond to adrenocorticotropic hormone properly, leading to low cortisol, but not corticosterone production, and …

Complex I Inhibitor Of Oxidative Phosphorylation In Advanced Solid Tumors And Acute Myeloid Leukemia: Phase I Trials, Timothy A Yap, Naval Daver, Mikhila Mahendra, Jixiang Zhang, Carlos Kamiya-Matsuoka, Funda Meric-Bernstam, Hagop M Kantarjian, Farhad Ravandi, Meghan E Collins, Maria Emilia Di Francesco, Ecaterina E Dumbrava, Siqing Fu, Sisi Gao, Jason P Gay, Sonal Gera, Jing Han, David S Hong, Elias J Jabbour, Zhenlin Ju, Daniel D Karp, Alessia Lodi, Jennifer R Molina, Natalia Baran, Aung Naing, Maro Ohanian, Shubham Pant, Naveen Pemmaraju, Prithviraj Bose, Sarina A Piha-Paul, Jordi Rodon, Carolina Salguero, Koji Sasaki, Anand K Singh, Vivek Subbiah, Apostolia M Tsimberidou, Quanyun A Xu, Musa Yilmaz, Qi Zhang, Yuan Li, Christopher A Bristow, Meenakshi B Bhattacharjee, Stefano Tiziani, Timothy P Heffernan, Christopher P Vellano, Philip Jones, Cobi J Heijnen, Annemieke Kavelaars, Joseph R Marszalek, Marina Konopleva

Faculty, Staff and Student Publications

Although targeting oxidative phosphorylation (OXPHOS) is a rational anticancer strategy, clinical benefit with OXPHOS inhibitors has yet to be achieved. Here we advanced IACS-010759, a highly potent and selective small-molecule complex I inhibitor, into two dose-escalation phase I trials in patients with relapsed/refractory acute myeloid leukemia (NCT02882321, n = 17) and advanced solid tumors (NCT03291938, n = 23). The primary endpoints were safety, tolerability, maximum tolerated dose and recommended phase 2 dose (RP2D) of IACS-010759. The PK, PD, and preliminary antitumor activities of IACS-010759 in patients were also evaluated as secondary endpoints in both clinical trials. IACS-010759 had a narrow …

Feasibility Of Quantitative Diffusion-Weighted Imaging During Intra-Procedural Mri-Guided Brachytherapy Of Locally Advanced Cervical And Vaginal Cancers, Megan C Jacobsen, Bastien Rigaud, Samantha J Simiele, Gaiane M Rauch, Matthew S Ning, Sastry Vedam, Ann H Klopp, R Jason Stafford, Kristy K Brock, Aradhana M Venkatesan

Faculty, Staff and Student Publications

Purpose: To determine the feasibility of quantitative apparent diffusion coefficient (ADC) acquisition during magnetic resonance imaging-guided brachytherapy (MRgBT) using reduced field-of-view (rFOV) diffusion-weighted imaging (DWI).

Methods and materials: T2-weighted (T2w) MR and full-FOV single-shot echo planar (ssEPI) DWI were acquired in 7 patients with cervical or vaginal malignancy at baseline and prior to brachytherapy, while rFOV-DWI was acquired during MRgBT following brachytherapy applicator placement. The gross target volume (GTV) was contoured on the T2w images and registered to the ADC map. Voxels at the GTV's maximum Maurer distance comprised a central sub-volume (GTVcenter). Contour ADC mean and standard deviation were …

The Role Of Non-Coding Rnas In Chromosomal Instability In Cancer, Swati Mohapatra, Melanie Winkle, Anh N Ton, Dien Nguyen, George A Calin

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Chromosomal instability (CIN) is characterized by an increased frequency of changes in chromosome structure or number and is regarded as a hallmark of cancer. CIN plays a prevalent role in tumorigenesis and cancer progression by assisting the cancer cells' phenotypic adaptation to stress, which have been tightly linked to therapy resistance and metastasis. Both CIN-inducing and CIN-repressing agents are being clinically tested for the treatment of cancer to increase CIN levels to unsustainable levels leading to cell death or to decrease CIN levels to limit the development of drug resistance, respectively. Non-coding RNAs (ncRNAs) including microRNAs and long ncRNAs (lncRNAs) …

Role Of Sentinel Lymph Node Biopsy For Oral Squamous Cell Carcinoma: Current Evidence And Future Challenges, Sophie S Jang, Morgan E Davis, David R Vera, Stephen Y Lai, Theresa W Guo

Faculty, Staff and Student Publications

Sentinel lymph node biopsy (SLNB) has been used across oncological specialties for prognostication, staging, and identification of occult nodal metastasis. Recent studies demonstrated the potential clinical utility of SLNB in oral cavity squamous cell carcinoma (OCSCC). Elective neck dissection is the current standard of care in early management of OCSCC with depth of invasion greater than 2-4 mm; however, majority of patients ultimately do not have nodal disease on final pathology. SLNB is an alternative procedure widely adopted in early cancer management in many oncological subspecialities. Several considerations such as depth of invasion, nodal mapping, histopathology methods, operator variability, postoperative …

The Contemporary Management Of Cancers Of The Sinonasal Tract In Adults, Rajat Thawani, Myung Sun Kim, Asad Arastu, Zizhen Feng, Malinda T West, Nicholas F Taflin, Kyaw Zin Thein, Ryan Li, Mathew Geltzeiler, Nancy Lee, Clifton David Fuller, Jennifer R Grandis, Charalampos S Floudas, Michael C Heinrich, Ehab Hanna, Ravi A Chandra

Faculty, Staff and Student Publications

Sinonasal malignancies make up <5% of all head and neck neoplasms, with an incidence of 0.5-1.0 per 100,000. The outcome of these rare malignancies has been poor, whereas significant progress has been made in the management of other cancers. The objective of the current review was to describe the incidence, causes, presentation, diagnosis, treatment, and recent developments of malignancies of the sinonasal tract. The diagnoses covered in this review included sinonasal undifferentiated carcinoma, sinonasal adenocarcinoma, sinonasal squamous cell carcinoma, and esthesioneuroblastoma, which are exclusive to the sinonasal tract. In addition, the authors covered malignances that are likely to be encountered in the sinonasal tract-primary mucosal melanoma, NUT (nuclear protein of the testis) carcinoma, and extranodal natural killer cell/T-cell lymphoma. For the purpose of keeping this review as concise and focused as possible, sarcomas and malignancies that can be classified as salivary gland neoplasms were excluded.

Head And Neck Cancer Predictive Risk Estimator To Determine Control And Therapeutic Outcomes Of Radiotherapy (Hnc-Predictor): Development, International Multi-Institutional Validation, And Web Implementation Of Clinic-Ready Model-Based Risk Stratification For Head And Neck Cancer, Lisanne V Van Dijk, Abdallah Sr Mohamed, Sara Ahmed, Nafiul Nipu, G Elisabeta Marai, Kareem Wahid, Nanna M Sijtsema, Brandon Gunn, Adam S Garden, Amy Moreno, Andrew J Hope, Johannes A Langendijk, Clifton D Fuller

Faculty, Staff and Student Publications

Background: Personalised radiotherapy can improve treatment outcomes of patients with head and neck cancer (HNC), where currently a 'one-dose-fits-all' approach is the standard. The aim was to establish individualised outcome prediction based on multi-institutional international 'big-data' to facilitate risk-based stratification of patients with HNC.

Methods: The data of 4611 HNC radiotherapy patients from three academic cancer centres were split into four cohorts: a training (n = 2241), independent test (n = 786), and external validation cohorts 1 (n = 1087) and 2 (n = 497). Tumour- and patient-related clinical variables were considered in a machine learning pipeline to predict overall …