Medical Specialties Commons^™

Reducing Frame Rate And Pulse Rate For Routine Diagnostic Cerebral Angiography: Alara Principles In Practice, Arvin R Wali, Sarath Pathuri, Michael G Brandel, Ryan W Sindewald, Brian R Hirshman, Javier A Bravo, Jeffrey A Steinberg, Scott E Olson, Jeffrey S Pannell, Alexander Khalessi, David Santiago-Dieppa

Faculty, Staff and Student Publications

Objective: Diagnostic cerebral angiograms (DCAs) are widely used in neurosurgery due to their high sensitivity and specificity to diagnose and characterize pathology using ionizing radiation. Eliminating unnecessary radiation is critical to reduce risk to patients, providers, and health care staff. We investigated if reducing pulse and frame rates during routine DCAs would decrease radiation burden without compromising image quality.

Methods: We performed a retrospective review of prospectively acquired data after implementing a quality improvement protocol in which pulse rate and frame rate were reduced from 15 p/s to 7.5 p/s and 7.5 f/s to 4.0 f/s respectively. Radiation doses and …

Examining Psychometric Properties Of The Metacognitions About Smoking Questionnaire Among Young E-Cigarette Users, Aslesha Sumbe, Robert Suchting, Baojiang Chen, Anna V Wilkinson, Bara Bataineh, Stephanie L Clendennen, Melissa B Harrell

Faculty, Staff and Student Publications

Objective: Metacognition can be understood as 'cognition of cognition' or 'thinking about thinking'. Metacognition research has primarily focused on cigarette smoking, while e-cigarette use has been relatively unexplored. The study sought to examine the properties of the Metacognitions about Smoking Questionnaire (MSQ), as it was adapted for use among adolescent and young adult e-cigarette users. Further, the study sought to examine the ability of the Metacognitions about Smoking Questionnaire (MSQ) to predict past 30-day e-cigarette use among adolescent and young adult e-cigarette users.

Methods: The study analyzed data collected by the Texas Adolescent Tobacco and Marketing Surveillance System (TATAMS) in …

Corrigendum To 'Molecular Identity Changes Of Tumor-Associated Macrophages And Microglia After Magnetic Resonance Imaging-Guided Focused Ultrasound-Induced Blood-Brain Barrier Opening In A Mouse Glioblastoma Model' [Ultrasound In Med & Biol 49 (2023) 1082-1090], Yanrong Zhang, Jing Wang, Sara Natasha Ghobadi, Haiyan Zhou, Ai Huang, Marco Gerosa, Qingyi Hou, Olivier Keunen, Anna Golebiewska, Frezghi G Habte, Gerald A Grant, Ramasamy Paulmurugan, Kevin S Lee, Max Wintermark

Faculty, Staff and Student Publications

No abstract provided.

Identifying A Stable And Generalizable Factor Structure Of Major Depressive Disorder Across Three Large Longitudinal Cohorts, Vincent W S Tseng, Jordan A Tharp, Jacob E Reiter, Weston Ferrer, David S Hong, P Murali Doraiswamy, Stefanie Nickels

Faculty, Staff and Student Publications

The Patient Health Questionnaire 9 (PHQ-9) is the current standard outpatient screening tool for measuring and tracking the nine symptoms of major depressive disorder (MDD). While the PHQ-9 was originally conceptualized as a unidimensional measure, it has become clear that MDD is not a monolithic construct, as evidenced by high comorbidities with other theoretically distinct diagnoses and common symptom overlap between depression and other diagnoses. Therefore, identifying reliable and temporally stable subfactors of depressive symptoms could allow research and care to be tailored to different depression phenotypes. This study improved on previous factor analysis studies of the PHQ-9 by leveraging …

Glycoprotein Nonmetastatic Melanoma Protein B (Gpnmb) Immunohistochemistry Can Be A Useful Ancillary Tool To Identify Perivascular Epithelioid Cell Tumor, Sintawat Wangsiricharoen, Davis R Ingram, Rohini R Morey, Khalida Wani, Alexander J Lazar, Wei-Lien Wang

Faculty, Staff and Student Publications

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors that express smooth muscle and melanocytic makers. Diagnosis of PEComas can be challenging due to focal or lost expression of traditional immunohistochemical markers, limited availability of molecular testing, and morphological overlap with much more common smooth muscle tumors. This study evaluates the use of glycoprotein nonmetastatic melanoma protein B (GPNMB) immunohistochemical staining as a surrogate marker for TSC1/2/MTOR alteration or TFE3 rearrangement to differentiate PEComas from other mesenchymal tumors. Cathepsin K was also assessed for comparison. A total of 399 tumors, including PEComas, alveolar soft part sarcomas, and other histologic PEComa …

Polygenic Risk Scores, Radiation Treatment Exposures And Subsequent Cancer Risk In Childhood Cancer Survivors, Todd M Gibson, Danielle M Karyadi, Stephen W Hartley, Michael A Arnold, Amy Berrington De Gonzalez, Miriam R Conces, Rebecca M Howell, Vidushi Kapoor, Wendy M Leisenring, Joseph P Neglia, Joshua N Sampson, Lucie M Turcotte, Stephen J Chanock, Gregory T Armstrong, Lindsay M Morton

Faculty, Staff and Student Publications

Survivors of childhood cancer are at increased risk for subsequent cancers attributable to the late effects of radiotherapy and other treatment exposures; thus, further understanding of the impact of genetic predisposition on risk is needed. Combining genotype data for 11,220 5-year survivors from the Childhood Cancer Survivor Study and the St Jude Lifetime Cohort, we found that cancer-specific polygenic risk scores (PRSs) derived from general population, genome-wide association study, cancer loci identified survivors of European ancestry at increased risk of subsequent basal cell carcinoma (odds ratio per s.d. of the PRS: OR = 1.37, 95% confidence interval (CI) = 1.29-1.46), …

Targeted Inhibition Of Scfskp2 Confers Anti-Tumor Activities Resulting In A Survival Benefit In Osteosarcoma, Jichuan Wang, Alexander Ferrena, Ranxin Zhang, Swapnil Singh, Valentina Viscarret, Waleed Al-Harden, Osama Aldahamsheh, Hasibagan Borjihan, Amit Singla, Simon Yaguare, Janet Tingling, Xiaolin Zi, Yungtai Lo, Richard Gorlick, Edward L Schwartz, Hongling Zhao, Rui Yang, David S Geller, Deyou Zheng, Bang H Hoang

Faculty, Staff and Student Publications

Osteosarcoma(OS) is a highly aggressive bone cancer for which treatment has remained essentially unchanged for decades. Although OS is characterized by extensive genomic heterogeneity and instability, RB1 and TP53 have been shown to be the most commonly inactivated tumor suppressors in OS. We previously generated a mouse model with a double knockout (DKO) of Rb1 and Trp53 within cells of the osteoblastic lineage, which largely recapitulates human OS with nearly complete penetrance. SKP2 is a repression target of pRb and serves as a substrate recruiting subunit of the SCFSKP2 complex. In addition, SKP2 plays a central role in regulating the …

Cardiovascular Events After Cancer Immunotherapy As Oncologic Emergencies: Analyses Of 610 Head And Neck Cancer Patients Treated With Immune Checkpoint Inhibitors, Cielito C Reyes-Gibby, Aiham Qdaisat, Renata Ferrarotto, Anecita Fadol, Jason J Bischof, Christopher J Coyne, Demis N Lipe, Ehab Y Hanna, Sanjay Shete, Jun-Ichi Abe, Sai-Ching J Yeung

Faculty, Staff and Student Publications

Background: Cardio-oncology and emergency medicine are closely collaborative, as many cardiac events in cancer patients require evaluation and treatment in the emergency department (ED). Immune checkpoint inhibitors (ICIs) have become a common treatment for patients with head and neck cancer (HNC). However, the immune-related adverse events (irAEs) from ICIs can be clinically significant.

Methods: We reviewed and analyzed cardiovascular diagnoses among HNC patients who received ICI during the period April 1, 2016-December 31, 2020 in a large tertiary cancer center. Demographics, clinical and cancer-related data were abstracted, and billing databases were queried for cardiovascular disease (CVD)-related diagnosis using International Classification …

Empirically Derived Principles For Research Funding Success: A Primer For Early Career Academic Investigators, Kareem A Wahid, Michael K Rooney, Jillian R Gunther, Amy C Moreno, Chelsea C Pinnix, Charles R Thomas, Clifton D Fuller

Faculty, Staff and Student Publications

No abstract provided.

Polygenic Risk Scores, Radiation Treatment Exposures And Subsequent Cancer Risk In Childhood Cancer Survivors, Todd M Gibson, Danielle M Karyadi, Stephen W Hartley, Michael A Arnold, Amy Berrington De Gonzalez, Miriam R Conces, Rebecca M Howell, Vidushi Kapoor, Wendy M Leisenring, Joseph P Neglia, Joshua N Sampson, Lucie M Turcotte, Stephen J Chanock, Gregory T Armstrong, Lindsay M Morton

Faculty, Staff and Student Publications

Survivors of childhood cancer are at increased risk for subsequent cancers attributable to the late effects of radiotherapy and other treatment exposures; thus, further understanding of the impact of genetic predisposition on risk is needed. Combining genotype data for 11,220 5-year survivors from the Childhood Cancer Survivor Study and the St Jude Lifetime Cohort, we found that cancer-specific polygenic risk scores (PRSs) derived from general population, genome-wide association study, cancer loci identified survivors of European ancestry at increased risk of subsequent basal cell carcinoma (odds ratio per s.d. of the PRS: OR = 1.37, 95% confidence interval (CI) = 1.29-1.46), …

Bardoxolone Methyl Ameliorates Chemotherapy-Induced Neuropathic Pain By Activation Of Phosphorylated Nuclear Factor Erythroid 2-Related Factor 2 In The Dorsal Root Ganglia, Hee Kee Kim, Qi Wang, Seon-Hee Hwang, Patrick M Dougherty, Jing Wang, Salahadin Abdi

Faculty, Staff and Student Publications

Background: Many chemotherapeutic drugs, including paclitaxel, produce neuropathic pain in patients with cancer, which is a dose-dependent adverse effect. Such chemotherapy-induced neuropathic pain (CINP) is difficult to treat with existing drugs. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator of antioxidative responses and activates phosphorylated Nrf2 (pNrf2). We determined the analgesic effects of bardoxolone methyl (BM), an Nrf2 activator, and the role of pNrf2 on CINP.

Methods: CINP was induced in rats by intraperitoneally injecting paclitaxel on 4 alternate days in rats. BM was injected systemically as single or repeated injections after pain fully developed. RNA transcriptome, …

Surrogate Endpoints In Clinical Trials Of P16-Positive Squamous Cell Carcinoma Of The Oropharynx: An Individual Patient Data Meta-Analysis, Laila A Gharzai, Emily Morris, Krithika Suresh, Phuc Felix Nguyen-Tân, David I Rosenthal, Maura L Gillison, Paul M Harari, Adam S Garden, Shlomo Koyfman, Jimmy J Caudell, Christopher U Jones, Darrion L Mitchell, Greg Krempl, John A Ridge, Michael F Gensheimer, James A Bonner, Edith Filion, Neal E Dunlap, William A Stokes, Quynh-Thu Le, Pedro Torres-Saavedra, Michelle Mierzwa, Matthew J Schipper

Faculty, Staff and Student Publications

Background: The increased incidence of human papillomavirus (HPV)-related cancers has motivated efforts to optimise treatment for these patients with excellent prognosis. Validation of surrogates for overall survival could expedite the investigation of new therapies. We sought to evaluate candidate intermediate clinical endpoints in trials assessing definitive treatment of p16-positive oropharyngeal cancer with chemotherapy or radiotherapy.

Methods: We did a retrospective review of five multicentre, randomised trials (NRG/RTOG 9003, 0129, 0234, 0522, and 1016) that tested radiotherapy with or without chemotherapy in patients (aged ≥18 years) with p16-positive localised head or neck squamous-cell carcinomas. Eight intermediate clinical endpoints were considered as …

Image-Based Multiplex Immune Profiling Of Cancer Tissues: Translational Implications A Report Of The International Immuno-Oncology Biomarker Working Group On Breast Cancer, Chowdhury Arif Jahangir, David B Page, Glenn Broeckx, Claudia A Gonzalez, Caoimbhe Burke, Clodagh Murphy, Jorge S Reis-Filho, Amy Ly, Paul W Harms, Rajarsi R Gupta, Michael Vieth, Akira I Hida, Mohamed Kahila, Zuzana Kos, Paul J Van Diest, Sara Verbandt, Jeppe Thagaard, Reena Khiroya, Khalid Abduljabbar, Gabriela Acosta Haab, Balazs Acs, Sylvia Adams, Jonas S Almeida, Isabel Alvarado-Cabrero, Farid Azmoudeh-Ardalan, Sunil Badve, Nurkhairul Bariyah Baharun, Enrique R Bellolio, Vydehi Bheemaraju, Kim Rm Blenman, Luciana Botinelly Mendonça Fujimoto, Octavio Burgues, Alexandros Chardas, Maggie Chon U Cheang, Francesco Ciompi, Lee Ad Cooper, An Coosemans, Germán Corredor, Flavio Luis Dantas Portela, Frederik Deman, Sandra Demaria, Sarah N Dudgeon, Mahmoud Elghazawy, Claudio Fernandez-Martín, Susan Fineberg, Stephen B Fox, Jennifer M Giltnane, Sacha Gnjatic, Paula I Gonzalez-Ericsson, Anita Grigoriadis, Niels Halama, Matthew G Hanna, Aparna Harbhajanka, Steven N Hart, Johan Hartman, Stephen Hewitt, Hugo M Horlings, Zaheed Husain, Sheeba Irshad, Emiel Am Janssen, Tatsuki R Kataoka, Kosuke Kawaguchi, Andrey I Khramtsov, Umay Kiraz, Pawan Kirtani, Liudmila L Kodach, Konstanty Korski, Guray Akturk, Ely Scott, Anikó Kovács, Anne-Vibeke Laenkholm, Corinna Lang-Schwarz, Denis Larsimont, Jochen K Lennerz, Marvin Lerousseau, Xiaoxian Li, Anant Madabhushi, Sai K Maley, Vidya Manur Narasimhamurthy, Douglas K Marks, Elizabeth S Mcdonald, Ravi Mehrotra, Stefan Michiels, Durga Kharidehal, Fayyaz Ul Amir Afsar Minhas, Shachi Mittal, David A Moore, Shamim Mushtaq, Hussain Nighat, Thomas Papathomas, Frederique Penault-Llorca, Rashindrie D Perera, Christopher J Pinard, Juan Carlos Pinto-Cardenas, Giancarlo Pruneri, Lajos Pusztai, Nasir Mahmood Rajpoot, Bernardo Leon Rapoport, Tilman T Rau, Joana M Ribeiro, David Rimm, Anne Vincent-Salomon, Joel Saltz, Shahin Sayed, Evangelos Hytopoulos, Sarah Mahon, Kalliopi P Siziopikou, Christos Sotiriou, Albrecht Stenzinger, Maher A Sughayer, Daniel Sur, Fraser Symmans, Sunao Tanaka, Timothy Taxter, Sabine Tejpar, Jonas Teuwen, E Aubrey Thompson, Trine Tramm, William T Tran, Jeroen Van Der Laak, Gregory E Verghese, Giuseppe Viale, Noorul Wahab, Thomas Walter, Yannick Waumans, Hannah Y Wen, Wentao Yang, Yinyin Yuan, John Bartlett, Sibylle Loibl, Carsten Denkert, Peter Savas, Sherene Loi, Elisabeth Specht Stovgaard, Roberto Salgado, William M Gallagher, Arman Rahman

Faculty, Staff and Student Publications

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour …

The Risk And Burden Of Thromboembolic And Hemorrhagic Events In Patients With Malignant Gliomas Receiving Bevacizumab, Pushan Dasgupta, Alexander Ou, Heather Lin, Timothy Gregory, Kristin D Alfaro-Munoz, Ying Yuan, Vahid Afshar-Khargan, Carlos Kamiya-Matsuoka, Justin F Rousseau, Nazanin K Majd

Faculty, Staff and Student Publications

Purpose: Bevacizumab has evolved as an integral treatment option for patients with high-grade gliomas. Little is known about clinical risk factors that predispose patients with high-grade gliomas receiving bevacizumab to VTE or ICH. We sought to characterize the clinical risk factors associated with risk of either event.

Methods: In this multi-institutional retrospective study, we first evaluated patients with high-grade gliomas who were treated with bevacizumab at University of Texas MD Anderson Cancer Center from 2015-2021. We compared clinical and treatment-related factors among three cohorts: those who developed VTE, ICH, or neither. We further compared survival outcomes of these patients from …

Personalized Accelerated Chemoradiation (Pacer) For Lung Cancer: Protocol For A Bayesian Optimal Phase I/Ii Trial, Caressa Hui, Eleanor Brown, Samantha Wong, Millie Das, Heather Wakelee, Joel Neal, Kavitha Ramchandran, Nathaniel J Myall, Daniel Pham, Lei Xing, Yong Yang, Nataliya Kovalchuk, Ying Yuan, Ying Lu, Michael Xiang, Alex Chin, Maximilian Diehn, Billy W Loo, Lucas K Vitzthum

Faculty, Staff and Student Publications

Introduction: Prior attempts to escalate radiation dose for non-small cell lung cancer (NSCLC) have not improved survival. Given the high risk for cardiopulmonary toxicity with treatment and heterogenous presentation of locally advanced NSCLC, it is unlikely that a single dose regimen is optimal for all patients. This phase I/II trial aims to evaluate a novel treatment approach where the level of accelerated hypofractionation is determined by the predicted toxicity from dose to organs at risk (OARs).

Methods: Patients ≥ 18 years old with lung cancer planned for fractionated radiotherapy to the lung with concurrent chemotherapy will be eligible. Radiation therapy …

A Phase I Study Of Docetaxel Plus Synthetic Lycopene In Metastatic Prostate Cancer Patients, Michael B Lilly, Chunli Wu, Yu Ke, Wen-Pin Chen, Adam C Soloff, Kent Armeson, Noriko N Yokoyama, Xiaotian Li, Liankun Song, Ying Yuan, Christine E Mclaren, Xiaolin Zi

Faculty, Staff and Student Publications

Purpose: Our preclinical studies showed that lycopene enhanced the anti-prostate cancer efficacy of docetaxel in animal models. A phase I trial (NCT0149519) was conducted to identify an optimum dose of synthetic lycopene in combination with docetaxel (and androgen blockade [androgen deprivation therapy, ADT]), and to evaluate its effect on the safety and pharmacokinetics of docetaxel in men with metastatic prostate cancer.

Methods: Subjects were treated with 21-day cycles of 75 mg/m2 docetaxel (and ADT), plus lycopene at 30, 90 or 150 mg/day. A Bayesian model averaging continual reassessment method was used to guide dose escalation. Pharmacokinetics of docetaxel …

Prenatal Vs Postnatal Diagnosis Of 22q112 Deletion Syndrome: Cardiac And Noncardiac Outcomes Through 1 Year Of Age, Lindsay R Freud, Stephanie Galloway, T Blaine Crowley, Julie Moldenhauer, Ann Swillen, Jeroen Breckpot, Antoni Borrell, Neeta L Vora, Bettina Cuneo, Hilary Hoffman, Lisa Gilbert, Beata Nowakowska, Maciej Geremek, Anna Kutkowska-Kaźmierczak, Joris R Vermeesch, Koen Devriendt, Tiffany Busa, Sabine Sigaudy, Trisha Vigneswaran, John M Simpson, Jeffrey Dungan, Nina Gotteiner, Karl-Philipp Gloning, Maria Cristina Digilio, Marta Unolt, Carolina Putotto, Bruno Marino, Gabriela Repetto, Magdalena Fadic, Sixto Garcia-Minaur, Ana Achón Buil, Mary Ann Thomas, Deborah Fruitman, Taylor Beecroft, Pui Wah Hui, Solveig Oskarsdottir, Rachael Bradshaw, Amanda Criebaum, Mary E Norton, Tiffany Lee, Miwa Geiger, Leslie Dunnington, Jacqueline Isaac, Louise Wilkins-Haug, Lindsey Hunter, Claudia Izzi, Marika Toscano, Tullio Ghi, Julie Mcglynn, Francesca Romana Grati, Beverly S Emanuel, Kimberly Gaiser, J William Gaynor, Elizabeth Goldmuntz, Daniel E Mcginn, Erica Schindewolf, Oanh Tran, Elaine H Zackai, Qi Yan, Anne S Bassett, Ronald Wapner, Donna M Mcdonald-Mcginn

Faculty, Staff and Student Publications

Background: The 22q11.2 deletion syndrome is the most common microdeletion syndrome and is frequently associated with congenital heart disease. Prenatal diagnosis of 22q11.2 deletion syndrome is increasingly offered. It is unknown whether there is a clinical benefit to prenatal detection as compared with postnatal diagnosis.

Objective: This study aimed to determine differences in perinatal and infant outcomes between patients with prenatal and postnatal diagnosis of 22q11.2 deletion syndrome.

Study design: This was a retrospective cohort study across multiple international centers (30 sites, 4 continents) from 2006 to 2019. Participants were fetuses, neonates, or infants with a genetic diagnosis of 22q11.2 …

Migraines, Vasomotor Symptoms, And Cardiovascular Disease In The Coronary Artery Risk Development In Young Adults Study, Catherine Kim, Pamela J Schreiner, Zhe Yin, Rachael Whitney, Stephen Sidney, Imo Ebong, Deborah A Levine

Faculty, Staff and Student Publications

Objective: To examine whether vasomotor symptoms (VMS) and migraine headaches, hypothesized to be vasoactive conditions, are associated with greater risk for cardiovascular disease (CVD) events including strokes.

Methods: We performed a secondary data analysis of a subset of women (n = 1,954) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based cohort, which began data collection at 18 to 30 y of age. We examined whether migraine headaches and VMS trajectories (characterized as minimal, increasing, and persistent) at CARDIA year 15 examination were associated with higher risk of CVD events and stroke (both ischemic and hemorrhagic) …

Clinical And Dosimetric Results Of Proton Or Photon Radiation Therapy For Large (>5 Cm) Hepatocellular Carcinoma: A Retrospective Analysis, Rodney Cheng-En Hsieh, Ching-Hsin Lee, Hsiao-Chieh Huang, Shu-Wei Wu, Chen-Yu Chou, Sheng-Ping Hung, Chao-Wei Lee, Sunil Krishnan, Bhanu Prasad Venkatesulu, Jin-Chiao Lee, Yung-Chih Chou, Kun-Ming Chan, Po-Ting Lin, Wei-Chen Lee, Chen-Chun Lin, Shen-Yen Lin, Ji-Hong Hong

Faculty, Staff and Student Publications

Purpose: Our purpose was to report the clinical and dosimetric attributes of patients with large unresectable hepatocellular carcinoma (HCC) undergoing proton or photon radiation therapy.

Methods and materials: We retrospectively analyzed the outcomes and dosimetric indices of 159 patients with >5 cm nonmetastatic HCC who underwent definitive radiation therapy using either protons (N = 105) or photons (N = 54) between 2014 and 2018. Additional photon plans were performed in the 105 proton-treated patients using the same dose prescription criteria for intragroup dosimetric comparison.

Results: After a median follow-up of 47 months, patients with biologically effective dose (BED10) ≥ 75 …

Stroke And The Microbiome, Anik Banerjee, Swati Mohapatra, Louise D Mccullough

Faculty, Staff and Student Publications

No abstract provided.

Peroxisome Proliferator-Activated Receptors As Therapeutic Target For Cancer, Yuqing Wang, Feifei Lei, Yiyun Lin, Yuru Han, Lei Yang, Huabing Tan

Faculty, Staff and Student Publications

Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor family. There are three subtypes of PPARs, including PPAR-α, PPAR-β/δ and PPAR-γ. They are expressed in different tissues and act by regulating the expression of target genes in the form of binding to ligands. Various subtypes of PPAR have been shown to have significant roles in a wide range of biological processes including lipid metabolism, body energy homeostasis, cell proliferation and differentiation, bone formation, tissue repair and remodelling. Recent studies have found that PPARs are closely related to tumours. They are involved in cancer cell growth, angiogenesis and …

Preclinical Efficacy Of Targeting Epigenetic Mechanisms In Aml With 3q26 Lesions And Evi1 Overexpression, Christine E Birdwell, Warren Fiskus, Tapan M Kadia, Christopher P Mill, Koji Sasaki, Naval Daver, Courtney D Dinardo, Naveen Pemmaraju, Gautam Borthakur, John A Davis, Kaberi Das, Sunil Sharma, Stephen Horrigan, Xinjia Ruan, Xiaoping Su, Joseph D Khoury, Hagop Kantarjian, Kapil N Bhalla

Faculty, Staff and Student Publications

AML with chromosomal alterations involving 3q26 overexpresses the transcription factor (TF) EVI1, associated with therapy refractoriness and inferior overall survival in AML. Consistent with a CRISPR screen highlighting BRD4 dependency, treatment with BET inhibitor (BETi) repressed EVI1, LEF1, c-Myc, c-Myb, CDK4/6, and MCL1, and induced apoptosis of AML cells with 3q26 lesions. Tegavivint (TV, BC-2059), known to disrupt the binding of nuclear β-catenin and TCF7L2/LEF1 with TBL1, also inhibited co-localization of EVI1 with TBL1 and dose-dependently induced apoptosis in AML cell lines and patient-derived (PD) AML cells with 3q26.2 lesions. TV treatment repressed EVI1, attenuated enhancer activity at ERG, TCF7L2, …

Targeting Hypoxia-Inducible Factors: Therapeutic Opportunities And Challenges, Xiaoyi Yuan, Wei Ruan, Bentley Bobrow, Peter Carmeliet, Holger K Eltzschig

Faculty, Staff and Student Publications

Hypoxia-inducible factors (HIFs) are highly conserved transcription factors that are crucial for adaptation of metazoans to limited oxygen availability. Recently, HIF activation and inhibition have emerged as therapeutic targets in various human diseases. Pharmacologically desirable effects of HIF activation include erythropoiesis stimulation, cellular metabolism optimization during hypoxia and adaptive responses during ischaemia and inflammation. By contrast, HIF inhibition has been explored as a therapy for various cancers, retinal neovascularization and pulmonary hypertension. This Review discusses the biochemical mechanisms that control HIF stabilization and the molecular strategies that can be exploited pharmacologically to activate or inhibit HIFs. In addition, we examine …

A Phase 1 Trial Of 8-Chloro-Adenosine In Relapsed/Refractory Acute Myeloid Leukemia: An Evaluation Of Safety And Pharmacokinetics, Vinod Pullarkat, Lisa S Chen, Joycelynne Palmer, Jianying Zhang, Timothy W Synold, Ralf Buettner, Le Xuan Truong Nguyen, Guido Marcucci, Ni-Chun Tsai, Yan Wang, James O'Hearn, Varsha Gandhi, Steven T Rosen

Faculty, Staff and Student Publications

Background: This study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of 8-chloro-adenosine (8-Cl-Ado) in patients with relapsed/refractory acute myeloid leukemia (AML).

Methods: 8-Cl-Ado was administered daily for 5 days; the starting dose was 100 mg/m2 , the highest dose tested was 800 mg/m2 . The end points were toxicity, disease response, and PK/PD measurements.

Results: The predominant nonhematologic toxicity was cardiac with grade ≥3 toxicity. Plasma PK in all patients suggested heterogeneity among patients, yet, some dose-dependency for the accumulation of 8-Cl-Ado. Two 8-Cl-Ado metabolites accumulated at similar levels to 8-Cl-Ado. Cellular PK in eight patients indicated accumulation of …

Case Series: Stenotrophomonas Maltophilia In Pediatric Oncology Patients, Sanila Sarkar, Lea M Stitzlein, Emily Rav, Miriam B Garcia, Shehla Razvi, Michael Chang, Ramia Zakhour

Faculty, Staff and Student Publications

Background: Stenotrophomonas maltophilia is a bacterial pathogen that can be fatal in hospitalized and immunocompromised patients with mortality as high as 69%. Pediatric cancer patients often have risk factors that are common for this infection, making them particularly susceptible. Managing S. maltophilia is especially challenging as it has inherent resistance to several antibiotics. Furthermore, soft tissue infections in neutropenic patients may deviate from the typical clinical presentation of S. maltophilia.

Case details: This case series describes an in-depth examination of three cases involving immunocompromised pediatric patients with S. maltophilia infections. Each case exhibited a distinct clinical presentation, encompassing infection of …

The Status And Challenges For Prostate Stereotactic Body Radiation Therapy Treatments In United States Proton Therapy Centers: An Nrg Oncology Practice Survey, Jiajian Shen, Paige A Taylor, Carlos E Vargas, Minglei Kang, Jatinder Saini, Jun Zhou, Peilong Wang, Wei Liu, Charles B Simone, Ying Xiao, Liyong Lin

Faculty, Staff and Student Publications

Purpose: To report the current practice pattern of the proton stereotactic body radiation therapy (SBRT) for prostate treatments.

Materials and methods: A survey was designed to inquire about the practice of proton SBRT treatment for prostate cancer. The survey was distributed to all 30 proton therapy centers in the United States that participate in the National Clinical Trial Network in February, 2023. The survey focused on usage, patient selection criteria, prescriptions, target contours, dose constraints, treatment plan optimization and evaluation methods, patient-specific QA, and image-guided radiation therapy (IGRT) methods.

Results: We received responses from 25 centers (83% participation). Only 8 …

Comprehensive Analysis Identifies Variability In Pi3k Pathway Alterations In Triple-Negative Breast Cancer Subtypes, Reva K Basho, Li Zhao, Jason B White, Lei Huo, Roland L Bassett, Elizabeth A Mittendorf, Alastair Thompson, Jennifer K Litton, Naoto Ueno, Banu Arun, Bora Lim, Vicente Valero, Debu Tripathy, Jianhua Zhang, Beatriz E Adrada, Lumarie Santiago, Elizabeth Ravenberg, Sahil Seth, Clinton Yam, Stacy L Moulder, Senthil Damodaran

Faculty, Staff and Student Publications

Purpose: The PI3K pathway is frequently altered in triple-negative breast cancer (TNBC). Limited cell line and human data suggest that TNBC tumors characterized as mesenchymal (M) and luminal androgen receptor (LAR) subtypes have increased incidence of alterations in the PI3K pathway. The impact of PI3K pathway alterations across TNBC subtypes is poorly understood.

Methods: Pretreatment tumor was evaluated from operable TNBC patients enrolled on a clinical trial of neoadjuvant therapy (NAT; A Robust TNBC Evaluation fraMework to Improve Survival [ClinicalTrials.gov identifier: NCT02276443]). Tumors were characterized into seven TNBC subtypes per Pietenpol criteria (basal-like 1, basal-like 2, immunomodulatory, M, mesenchymal …

Management Of Incomplete Microcirculatory Reperfusion After Endovascular Thrombectomy: Focus On Inhibition Of The Glycoprotein Iib/Iiia Receptor Pathway, Neeharika Krothapalli, Thomas Ortel, Devin Mcbride, Adam De Havenon, Lauren H Sansing, David Hasan, Brian Mac Grory

Faculty, Staff and Student Publications

Endovascular thrombectomy (EVT) is one of the most effective therapies for acute ischemic stroke attributable to large-vessel occlusion but, despite successful treatment, there remains a significant number of patients with disability. The phenomenon of incomplete microcirculatory reperfusion or no reflow is thought to underlie a substantial proportion of cases with unfavorable outcome. This phenomenon likely arises from platelet aggregation and endothelial edema impacting the cerebral microvasculature, vessels that are below the resolution of digital subtraction angiography. Although incomplete microcirculatory reperfusion prevents tissue recovery and poses a significant clinical challenge, there are multiple therapeutic options administered early after recanalization that have …

Outcomes In 14 Live Births Resulting From Pegvaliase-Treated Pregnancies In Pku-Affected Females, Caide Bier, Kaelin Dickey, Brittan Bibb, Angela Crutcher, Rebecca Sponberg, Richard Chang, Monica Boyer, Laura Davis-Keppen, Cindy Matthes, Michelle Tharp, Danielle Vice, Erin Cooney, Megan Morand, Joseph Ray, Melissa Lah, Markey Mcnutt, Hans C Andersson

Faculty, Staff and Student Publications

Background: Adults with PKU have difficulty maintaining plasma phenylalanine (Phe) in the range that is safe for neurologic function. Elevated plasma Phe is a risk factor for congenital anomalies and developmental delay in offspring resulting from pregnancies with poor Phe control in women with PKU. Enzyme supplementation with pegvaliase allows adults with PKU to eat an unrestricted diet and have plasma Phe levels in a safe range for pregnancy but pegvaliase has not been approved for use in pregnant females with PKU. We report the results of chart review of 14 living offspring of females affected with PKU who were …

The Fatigue-Inducing Effects Of Cancer And Its Therapy Are Characterized By Decreased Physical Activity In The Absence Of Any Motivational Deficit, Thien T Phan, Kiersten S Scott, Brandon Chelette, A Phillip West, Robert Dantzer

Faculty, Staff and Student Publications

Although cancer and its therapy are well known to be associated with fatigue, the exact nature of cancer-related fatigue remains ill-defined. We previously reported that fatigue-like behavior induced independently by tumor growth and by the chemotherapeutic agent cisplatin is characterized by reduced voluntary wheel running and an intact motivation to expand effort for food rewards. The present set of experiments was initiated to characterize the functional consequences of fatigue induced by chemoradiotherapy in tumor-bearing mice and relate them to changes in the expression of genes coding for inflammation, mitochondria dynamics and metabolism. Two syngeneic murine models of cancer were selected …