Medicine and Health Sciences Commons^™

Tgfβ Signaling Links Early Life Endocrine-Disrupting Chemicals Exposure To Suppression Of Nucleotide Excision Repair In Rat Myometrial Stem Cells, Maria Victoria Bariani, Yan-Hong Cui, Mohamed Ali, Tao Bai, Sandra L Grimm, Cristian Coarfa, Cheryl L Walker, Yu-Ying He, Qiwei Yang, Ayman Al-Hendy

Faculty, Staff and Students Publications

Environmental exposure to endocrine-disrupting chemicals (EDCs) is linked to the development of uterine fibroids (UFs) in women. UFs, non-cancerous tumors, are thought to originate from abnormal myometrial stem cells (MMSCs). Defective DNA repair capacity may contribute to the emergence of mutations that promote tumor growth. The multifunctional cytokine TGFβ1 is associated with UF progression and DNA damage repair pathways. To investigate the impact of EDC exposure on TGFβ1 and nucleotide excision repair (NER) pathways, we isolated MMSCs from 5-month-old Eker rats exposed neonatally to diethylstilbestrol (DES), an EDC, or to vehicle (VEH). EDC-MMSCs exhibited overactivated TGFβ1 signaling and reduced mRNA …

Unveiling The Potential Application Of Intraoperative Brain Smear For Brain Tumor Diagnosis In Low-Middle-Income Countries: A Comprehensive Systematic Review, Muhammad Shakir, Ahmed Altaf, Hawra Hussain, Syed Muhammad Aqeel Abidi, Zoey Petitt, Mahnoor Tariq, Ahmed Gilani, Syed Ather Enam

Section of Neurosurgery

Background: Immediate intraoperative histopathological examination of tumor tissue is indispensable for a neurosurgeon to track surgical resection. A brain smear is a simple, rapid, and cost-effective technique, particularly important in the diagnosis of brain tumors. The study aims to determine the effectiveness of intraoperative brain smear in the diagnosis of brain tumors in low- and middle-income countries (LMICs), while also evaluating its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy.
Methods: A comprehensive search of the literature was conducted using PubMed, Scopus, and Google Scholar. The retrieved articles were independently screened by two reviewers. The …

Comparative Retrospective Study Of Proton Arc Planning With Elsa Algorithm And Impt With Monte Carlo Algorithm With Raystation Treatment Planning System, Matthew L. Carpenter Ms, Msha, Bsrt(R)(T)

Masters Projects

Proton arc therapy (PAT) will become widely available soon. It is crucial to determine if this technique and the associated calculation algorithms provided by treatment planning system vendors compete favorably with established proton therapy techniques like intensity modulated proton therapy (IMPT) and the Monte Carlo dose calculation algorithm used to compute IMPT doses in today’s clinic. RaySearch Laboratories have produced a modified Monte Carlo algorithm called ELSA.

ELSA stands for early layer spot assignment and is RaySearch Laboratories proposed solution to reduce optimization time during treatment planning for PAT. This research study will look at proton plan robustness to determine …

Structures Of Ctcf-Dna Complexes Including All 11 Zinc Fingers, Jie Yang, John R Horton, Bin Liu, Victor G Corces, Robert M Blumenthal, Xing Zhang, Xiaodong Cheng

Faculty, Staff and Student Publications

The CCCTC-binding factor (CTCF) binds tens of thousands of enhancers and promoters on mammalian chromosomes by means of its 11 tandem zinc finger (ZF) DNA-binding domain. In addition to the 12-15-bp CORE sequence, some of the CTCF binding sites contain 5' upstream and/or 3' downstream motifs. Here, we describe two structures for overlapping portions of human CTCF, respectively, including ZF1-ZF7 and ZF3-ZF11 in complex with DNA that incorporates the CORE sequence together with either 3' downstream or 5' upstream motifs. Like conventional tandem ZF array proteins, ZF1-ZF7 follow the right-handed twist of the DNA, with each finger occupying and recognizing …

Click Display: A Rapid And Efficient In Vitro Protein Display Method For Directed Evolution, Yu Zeng, Michael Woolley, Karuppiah Chockalingam, Benjamin Thomas, Srishtee Arora, Magnus Hook, Zhilei Chen

Faculty, Staff and Student Publications

We describe a novel method for in vitro protein display-click display-that does not depend on maintaining RNA integrity during biopanning and yields covalently linked protein-cDNA complexes from double-stranded input DNA within 2 h. The display is achieved in a one-pot format encompassing transcription, translation and reverse transcription reactions in series. Stable linkage between proteins and the encoding cDNA is mediated by a modified DNA linker-ML-generated via a click chemistry reaction between a puromycin-containing oligo and a cDNA synthesis primer. Biopanning of a click-displayed mock library coupled with next-generation sequencing analysis revealed >600-fold enrichment of target binders within a single round …

Modulation Of The Proteostasis Network Promotes Tumor Resistance To Oncogenic Kras Inhibitors, Xiangdong Lv, Xuan Lu, Jin Cao, Qin Luo, Yao Ding, Fanglue Peng, Apar Pataer, Dong Lu, Dong Han, Eric Malmberg, Doug W Chan, Xiaoran Wang, Sara R Savage, Sufeng Mao, Jingjing Yu, Fei Peng, Liang Yan, Huan Meng, Laure Maneix, Yumin Han, Yiwen Chen, Wantong Yao, Eric C Chang, Andre Catic, Xia Lin, George Miles, Pengxiang Huang, Zheng Sun, Bryan Burt, Huamin Wang, Jin Wang, Qizhi Cathy Yao, Bing Zhang, Jack A Roth, Bert W O'Malley, Matthew J Ellis, Mothaffar F Rimawi, Haoqiang Ying, Xi Chen

Faculty, Staff and Student Publications

Despite substantial advances in targeting mutant KRAS, tumor resistance to KRAS inhibitors (KRASi) remains a major barrier to progress. Here, we report proteostasis reprogramming as a key convergence point of multiple KRASi-resistance mechanisms. Inactivation of oncogenic KRAS down-regulated both the heat shock response and the inositol-requiring enzyme 1α (IRE1α) branch of the unfolded protein response, causing severe proteostasis disturbances. However, IRE1α was selectively reactivated in an ER stress-independent manner in acquired KRASi-resistant tumors, restoring proteostasis. Oncogenic KRAS promoted IRE1α protein stability through extracellular signal-regulated kinase (ERK)-dependent phosphorylation of IRE1α, leading to IRE1α disassociation from 3-hydroxy-3-methylglutaryl reductase degradation (HRD1) E3-ligase. In …

Braf V600e/Ras Mutations And Lynch Syndrome In Patients With Msi-H/Dmmr Metastatic Colorectal Cancer Treated With Immune Checkpoint Inhibitors, Raphael Colle, Sara Lonardi, Marine Cachanado, Michael J Overman, Elena Elez, Marwan Fakih, Francesca Corti, Priya Jayachandran, Magali Svrcek, Antoine Dardenne, Baptiste Cervantes, Alex Duval, Romain Cohen, Filippo Pietrantonio, Thierry André

Faculty, Staff and Student Publications

BACKGROUND: We pooled data from 2 cohorts of immune checkpoint inhibitors-treated microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer patients to evaluate the prognostic value of RAS/BRAFV600E mutations and Lynch syndrome (LS).

PATIENTS AND METHODS: Patients were defined as LS-linked if germline mutation was detected and as sporadic if loss of MLH1/PMS2 expression with BRAFV600E mutation and/or MLH1 promoter hypermethylation, or biallelic somatic MMR genes mutations were found. Progression-free survival (PFS) and overall survival (OS) were adjusted on prognostic modifiers selected on unadjusted analysis (P < .2) if limited number of events.

RESULTS: Of 466 included patients, 305 (65.4%) and 161 (34.5%) received, respectively, anti-PD1 alone and anti-PD1+anti-CTLA4 …

Paclitaxel With Or Without Cixutumumab As Second-Line Treatment Of Metastatic Esophageal Or Gastroesophageal Junction Cancer: A Randomized Phase Ii Ecog-Acrin Trial, Shannon Stockton, Paul Catalano, Steven J. Cohen, Barbara A, Burtness, Edith P. Mitchell, Efrat Dotan, Sam J. Lubner, Pankaj Kumar, Mary F. Mulcahy, George A. Fisher, Theodore L. Crandall, Al Benson

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients with advanced esophageal cancer carry poor prognoses; limited data exist to guide second-line therapy in the metastatic setting. Paclitaxel has been used yet is associated with limited efficacy. There is preclinical evidence of synergy between paclitaxel and cixutumumab, a monoclonal antibody targeting insulin-like growth factor-1 receptor. We conducted a randomized phase II trial of paclitaxel (arm A) versus paclitaxel plus cixutumumab (arm B) in the second-line for patients with metastatic esophageal or gastroesophageal junction (GEJ) cancers.

METHODS: The primary endpoint was progression-free survival (PFS); 87 patients (43 in arm A, 44 in arm B) were treated.

RESULTS: Median …

Five-Year Follow-Up Of Keynote-087: Pembrolizumab Monotherapy For Relapsed/Refractory Classical Hodgkin Lymphoma, Philippe Armand, Pier Luigi Zinzani, Hun Ju Lee, Nathalie A Johnson, Pauline Brice, John Radford, Vincent Ribrag, Daniel Molin, Theodoros P Vassilakopoulos, Akihiro Tomita, Bastian Von Tresckow, Margaret A Shipp, Alex F Herrera, Jianxin Lin, Eunhee Kim, Samhita Chakraborty, Patricia Marinello, Craig H Moskowitz

Faculty, Staff and Student Publications

Previous analyses of the phase 2 KEYNOTE-087 (NCT02453594) trial of pembrolizumab monotherapy demonstrated effective antitumor activity with acceptable safety in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL). However, long-term response durability and outcome of patients who receive a second course after treatment discontinuation after complete response (CR) remain of clinical interest. We present KEYNOTE-087 data after >5 years of median follow-up. Patients with R/R cHL and progressive disease (PD) after autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV; cohort 1), salvage chemotherapy and BV without ASCT (cohort 2), or ASCT without subsequent BV (cohort 3), received …

Seamless Phase Ii/Iii Design: A Useful Strategy To Reduce The Sample Size For Dose Optimization, Liyun Jiang, Ying Yuan

Faculty, Staff and Student Publications

Background: The traditional more-is-better dose selection paradigm, originally developed for cytotoxic chemotherapeutics, can be problematic when applied to the development of novel molecularly targeted agents. Recognizing this issue, the US Food and Drug Administration initiated Project Optimus to reform the dose optimization and selection paradigm in oncology drug development, emphasizing the need for greater attention to benefit-risk considerations.

Methods: We identify different types of phase II/III dose-optimization designs, classified according to trial objectives and endpoint types. Through computer simulations, we examine their operating characteristics and discuss the relevant statistical and design considerations for effective dose optimization.

Results: Phase II/III dose-optimization …

Clinically Conserved Genomic Subtypes Of Gastric Adenocarcinoma, Yun Seong Jeong, Young-Gyu Eun, Sung Hwan Lee, Sang-Hee Kang, Sun Young Yim, Eui Hyun Kim, Joo Kyung Noh, Bo Hwa Sohn, Seon Rang Woo, Moonkyoo Kong, Deok Hwa Nam, Hee-Jin Jang, Hyun-Sung Lee, Shumei Song, Sang Cheul Oh, Jeeyun Lee, Jaffer A Ajani, Ju-Seog Lee

Faculty, Staff and Student Publications

Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately …

Stem-Like Cd4+T Cells In Perivascular Tertiary Lymphoid Structures Sustain Autoimmune Vasculitis, Yuki Sato, Abhinav Jain, Shozo Ohtsuki, Hirohisa Okuyama, Ines Sturmlechner, Yoshinori Takashima, Kevin-Phu C Le, Melanie C Bois, Gerald J Berry, Kenneth J Warrington, Jörg J Goronzy, Cornelia M Weyand

Faculty, Staff and Student Publications

Autoimmune vasculitis of the medium and large elastic arteries can cause blindness, stroke, aortic arch syndrome, and aortic aneurysm. The disease is often refractory to immunosuppressive therapy and progresses over decades as smoldering aortitis. How the granulomatous infiltrates in the vessel wall are maintained and how tissue-infiltrating T cells and macrophages are replenished are unknown. Single-cell and whole-tissue transcriptomic studies of immune cell populations in vasculitic arteries identified a CD4+ T cell population with stem cell-like features. CD4+ T cells supplying the tissue-infiltrating and tissue-damaging effector T cells survived in tertiary lymphoid structures around adventitial vasa vasora, expressed the transcription …

Integrating Participant Feedback And Concerns To Improve Community And Individual Level Chemical Exposure Assessment Reports, Samantha M Samon, Michael Barton, Kim Anderson, Abiodun Oluyomi, Melissa Bondy, Georgina Armstrong, Diana Rohlman

Faculty, Staff and Students Publications

BACKGROUND: As exposure assessment has shifted towards community-engaged research there has been an increasing trend towards reporting results to participants. Reports aim to increase environmental health literacy, but this can be challenging due to the many unknowns regarding chemical exposure and human health effects. This includes when reports encompass a wide-range of chemicals, limited reference or health standards exist for those chemicals, and/or incompatibility of data generated from exposure assessment tools with published reference values (e.g., comparing a wristband concentration to an oral reference dose).

METHODS: Houston Hurricane Harvey Health (Houston-3H) participants wore silicone wristbands that were analyzed for 1,530 …

Patient-Reported Outcomes Of Omission Of Breast Surgery Following Neoadjuvant Systemic Therapy: A Nonrandomized Clinical Trial, Helen M Johnson, Heather Lin, Yu Shen, Emilia J Diego, Savitri Krishnamurthy, Wei T Yang, Benjamin D Smith, Vicente Valero, Anthony Lucci, Susie X Sun, Simona F Shaitelman, Melissa P Mitchell, Judy C Boughey, Richard L White, Gaiane M Rauch, Henry M Kuerer

Faculty, Staff and Student Publications

IMPORTANCE: Patients should have an active role in decisions about pursuing or forgoing specific therapies in treatment de-escalation trials.

OBJECTIVE: To evaluate longitudinal patient-reported outcomes (PROs) encompassing decisional comfort and health-related quality of life (HRQOL) among patients who elected to enroll in a clinical trial evaluating radiotherapy alone, without breast surgery, for invasive breast cancers with exceptional response to neoadjuvant systemic therapy (NST).

DESIGN, SETTING, AND PARTICIPANTS: Prospective, single-group, phase 2 clinical trial at 7 US medical centers. Women aged 40 years or older with invasive cT1-2 N0-1 M0 triple-negative or human epidermal growth factor receptor 2 (ERBB2)-positive breast cancer …

Conditional Risks Of Biochemical Failure And Prostate Cancer-Specific Death In Patients Undergoing External Beam Radiotherapy: A Secondary Analysis Of 2 Randomized Clinical Trials, Gregory S. Alexander, Rebecca F Krc, James W Assif, Kai Sun, Jason K Molitoris, Phuoc Tran, Zaker Rana, Søren M Bentzen, Mark V Mishra

Department of Radiation Oncology Faculty Papers

IMPORTANCE: As patients achieve years of survival after treatment for prostate cancer, the risk of biochemical failure (BF) or prostate cancer-specific death (PCSD) may evolve over time, with clinical relevance to both patients and clinicians.

OBJECTIVE: To determine conditional BF-free survival, PSCD, and overall survival estimates for patients with low- or intermediate-risk prostate cancer enrolled in the Radiation Therapy Oncology Group (RTOG) 0126 and RTOG 0415 clinical trials. A secondary objective was to determine whether prognostic factors at diagnosis remain relevant at later points in follow-up.

DESIGN, SETTING, AND PARTICIPANTS: A pooled secondary analysis of patients treated with external-beam radiotherapy …

Prognostic Evaluation Of Re-Resection For Recurrent Glioblastoma Using The Novel Rano Classification For Extent Of Resection: A Report Of The Rano Resect Group, Philipp Karschnia, Antonio Dono, Jacob S Young, Stephanie T Juenger, Nico Teske, Levin Häni, Tommaso Sciortino, Christine Y Mau, Francesco Bruno, Luis Nunez, Ramin A Morshed, Alexander F Haddad, Michael Weller, Martin Van Den Bent, Juergen Beck, Shawn Hervey-Jumper, Annette M Molinaro, Nitin Tandon, Roberta Rudà, Michael A Vogelbaum, Lorenzo Bello, Oliver Schnell, Stefan J Grau, Susan M Chang, Mitchel S Berger, Yoshua Esquenazi, Joerg-Christian Tonn

Faculty, Staff and Student Publications

BACKGROUND: The value of re-resection in recurrent glioblastoma remains controversial as a randomized trial that specifies intentional incomplete resection cannot be justified ethically. Here, we aimed to (1) explore the prognostic role of extent of re-resection using the previously proposed Response Assessment in Neuro-Oncology (RANO) classification (based upon residual contrast-enhancing (CE) and non-CE tumor), and to (2) define factors consolidating the surgical effects on outcome.

METHODS: The RANO resect group retrospectively compiled an 8-center cohort of patients with first recurrence from previously resected glioblastomas. The associations of re-resection and other clinical factors with outcome were analyzed. Propensity score-matched analyses were …

Epidermal Growth Factor Receptor-Targeted Neoantigen Peptide Vaccination For The Treatment Of Non-Small Cell Lung Cancer And Glioblastoma, Fenge Li, Huancheng Wu, Xueming Du, Yimo Sun, Barbara Nassif Rausseo, Amjad Talukder, Arjun Katailiha, Lama Elzohary, Yupeng Wang, Zhiyu Wang, Gregory Lizée

Faculty, Staff and Student Publications

The epidermal growth factor receptor (EGFR) plays crucial roles in several important biological functions such as embryogenesis, epithelial tissue development, and cellular regeneration. However, in multiple solid tumor types overexpression and/or activating mutations of the EGFR gene frequently occur, thus hijacking the EGFR signaling pathway to promote tumorigenesis. Non-small cell lung cancer (NSCLC) tumors in particular often contain prevalent and shared EGFR mutations that provide an ideal source for public neoantigens (NeoAg). Studies in both humans and animal models have confirmed the immunogenicity of some of these NeoAg peptides, suggesting that they may constitute viable targets for cancer immunotherapies. Peptide …

Genetic Susceptibility To Cognitive Decline Following Craniospinal Irradiation For Pediatric Central Nervous System Tumors, Austin L Brown, Pagna Sok, Kimberly P Raghubar, Philip J Lupo, Melissa A Richard, Alanna C Morrison, Jun J Yang, Clinton F Stewart, Mehmet Fatih Okcu, Murali M Chintagumpala, Amar Gajjar, Lisa S Kahalley, Heather Conklin, Michael E Scheurer

Faculty, Staff and Student Publications

BACKGROUND: Survivors of pediatric central nervous system (CNS) tumors treated with craniospinal irradiation (CSI) exhibit long-term cognitive difficulties. Goals of this study were to evaluate longitudinal effects of candidate and novel genetic variants on cognitive decline following CSI.

METHODS: Intelligence quotient (IQ), working memory (WM), and processing speed (PS) were longitudinally collected from patients treated with CSI (n = 241). Genotype-by-time interactions were evaluated using mixed-effects linear regression to identify common variants (minor allele frequency > 1%) associated with cognitive performance change. Novel variants associated with cognitive decline (P < 5 × 10-5) in individuals of European ancestry (n = 163) were considered replicated if they demonstrated consistent genotype-by-time interactions (P < .05) in individuals of non-European ancestries (n = 78) and achieved genome-wide statistical significance (P < 5 × 10-8) in a meta-analysis across ancestry groups.

RESULTS: Participants were mostly males (65%) diagnosed with embryonal tumors (98%) at …

Low-Grade Serous Ovarian Cancer: Expert Consensus Report On The State Of The Science, Rachel N Grisham, Brian M Slomovitz, Nicole Andrews, Susana Banerjee, Jubilee Brown, Mark S Carey, Herman Chui, Robert L Coleman, Amanda N Fader, Stephanie Gaillard, Charlie Gourley, Anil K Sood, Bradley J Monk, Kathleen N Moore, Isabelle Ray-Coquard, Ie-Ming Shih, Shannon N Westin, Kwong-Kwok Wong, David M Gershenson

Faculty, Staff and Student Publications

Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade …

Prevalence Of Depression In Patients With Hematologic Diseases In Marrakesh, Morocco: A Single Center Experience, Fatima Zahra Lahlimi, Oumaima Maghnouj, Khawla Khalil, Safaa Chaabane, Illias Tazi

Journal of Community Hospital Internal Medicine Perspectives

Depression in patients with cancer influences negatively their physical symptoms, treatment success, coping, and their quality of life, and it is associated with increased mortality. Reported prevalence of emotional distress in patients followed in hematology varies widely across studies. The present study aimed to investigate the prevalence of depression, and to explore the possible associated factors in patients followed in a hematological department Method: in this descriptive cross-sectional study among patients admitted to the hematology department in the University Hospital Mohammed VI of Marrakech, between August 2020 and December 2020, depression symptoms were assessed using Mini International Neuropsychiatric Interview test …

International Consensus Statement On Allergy And Rhinology: Sinonasal Tumors, Edward C. Kuan, Eric W. Wang, Nithin D. Adappa, Daniel M. Beswick, Nyall R. London, Shirley Y. Su, Marilene B. Wang, Waleed M. Abuzeid, Borislav Alexiev, Jeremiah A. Alt, Paolo Antognoni, Michelle Alonso-Basanta, Pete S. Batra, Mihir Bhayani, Diana Bell, Manuel Bernal-Sprekelsen, Christian S. Betz, Jean Yves Blay, Benjamin S. Bleier, Juliana Bonilla-Velez, Claudio Callejas, Ricardo L. Carrau, Roy R. Casiano, Paolo Castelnuovo, Rakesh K. Chandra, Vasileios Chatzinakis, Simon B. Chen, Alexander G. Chiu, Stephen C. Hernandez, Et Al

School of Medicine Faculty Publications

Background; Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology; Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field. Methods; In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the …

Taz2 Truncation Confers Overactivation Of P300 And Cellular Vulnerability To Hdac Inhibition, Longxia Xu, Hongwen Xuan, Wei He, Liang Zhang, Mengying Huang, Kuai Li, Hong Wen, Han Xu, Xiaobing Shi

Faculty, Staff and Student Publications

The histone acetyltransferase p300/CBP is composed of several conserved domains, among which, the TAZ2 domain is known as a protein-protein interaction domain that binds to E1A and various transcription factors. Here we show that TAZ2 has a HAT autoinhibitory function. Truncating p300/CBP at TAZ2 leads to hyperactive HAT and elevated histone H3K27 and H3K18 acetylation in cells. Mechanistically, TAZ2 cooperates with other HAT neighboring domains to maintain the HAT active site in a 'closed' state. Truncating TAZ2 or binding of transcription factors to TAZ2 induces a conformational change that 'opens' the active site for substrate acetylation. Importantly, genetic mutations that …

From The Lung To The Finger: An Unusual Presentation Of Adenosquamous Cell Carcinoma, Preeti Badve, Md, Sussy Obando Lara, Md, Elisenda Valdez Pena, Md, Myriah Magaris, Do, Zunaira Naeem, Md, Charalambos Solomides, Md, Avnish Bhatia

Department of Medical Oncology Posters

Learning Objective

To recognize unusual presentations of metastatic lung disease.

Non-Contact Optical Spectroscopy For Tumor-Sensitive Diffuse Reflectance And Fluorescence Measurements On Murine Subcutaneous Tissue Models: Monte Carlo Modeling And Experimental Validations, Zahid Hasan, Pranto Soumik Saha, Madison O. Korfhage, Caigang Zhu

Markey Cancer Center Faculty Publications

Fiber-optic probes are commonly used in biomedical optical spectroscopy platforms for light delivery and collection. At the same time, it was reported that the inconsistent probe- sample contact could induce significant distortions in measured optical signals, which consequently cause large analysis errors. To address this challenge, non-contact optical spectroscopy has been explored for tissue characterizations. However, existing non-contact optical spectroscopy platforms primarily focused on diffuse reflectance measurements and may still use a fiber probe in which the probe was imaged onto the tissue surface using a lens, which serves as a non-contact probe for the measurements. Here, we report a …

Hospitalizations Among Adults With Ckd In Public Renal Specialty Practices: A Retrospective Study From Queensland, Australia, Vishal Diwan, Wendy E Hoy, Zaimin Wang, Jianzhen Zhang, Anne Cameron, Sree K Venuthurupalli, Robert G Fassett, Samuel Chan, Helen G Healy, Ken-Soon Tan, Richard Baer, Andrew J Mallett, Nicholas Gray, Murty Mantha, Roy Cherian, Clyson Mutatiri, Krishan Madhan, George Kan, Geoffrey Mitchell, Shahadat Hossain, Danielle Wu, Thin Han, Adrian Kark, Thomas Titus, Dwarakanatan Ranganathan, Ann Bonner, Sridevi Govindarajulu, Nhmrc Ckd.Cre And The Ckd.Qld Collaborative

Faculty, Staff and Student Publications

RATIONALE & OBJECTIVE: Little is known about hospital admissions in nondialysis patients with chronic kidney disease (CKD) before death or starting kidney replacement therapy (KRT).

STUDY DESIGN: Retrospective observational cohort study.

SETTING & PARTICIPANTS: Hospitalizations among 7,201 patients with CKD from 10 public renal clinics in Queensland (QLD), enrolled in the CKD.QLD registry starting in May 2011, were followed for 25,496.34 person-years until they started receiving KRT or died, or until June 30, 2018.

PREDICTORS: Demographic and clinical characteristics of patients with CKD.

OUTCOMES: Hospital admissions.

ANALYTICAL APPROACH: We evaluated the association of demographic and clinical features with hospitalizations, length …

Efficient Targeted Learning Of Heterogeneous Treatment Effects For Multiple Subgroups, Waverly Wei, Maya Petersen, Mark J Van Der Laan, Zeyu Zheng, Chong Wu, Jingshen Wang

Faculty, Staff and Student Publications

In biomedical science, analyzing treatment effect heterogeneity plays an essential role in assisting personalized medicine. The main goals of analyzing treatment effect heterogeneity include estimating treatment effects in clinically relevant subgroups and predicting whether a patient subpopulation might benefit from a particular treatment. Conventional approaches often evaluate the subgroup treatment effects via parametric modeling and can thus be susceptible to model mis-specifications. In this paper, we take a model-free semiparametric perspective and aim to efficiently evaluate the heterogeneous treatment effects of multiple subgroups simultaneously under the one-step targeted maximum-likelihood estimation (TMLE) framework. When the number of subgroups is large, we …

Mpla Case: How Do You Lead As A Lead Physicist?, Patricia Sansourekidou, Leonard Kim, Lee Xu, Mary Gronberg, Cassandra Stambaugh, Dongxu Wang

Faculty, Staff and Student Publications

This work of fiction is part of a case study series developed by the Medical Physics Leadership Academy (MPLA). It is intended to facilitate the discussion of the managerial and leadership challenges faced by a clinical medical physicist. In this case, a physicist David used to work in a clinic where he thrived and felt like a leader, despite not having the title. After a job change, he is now officially the "Lead Physicist" at a hospital newly affiliated with a large academic healthcare system. He believes he will be equally successful. Yet he struggles to bring about changes and …

Longitudinal Diffusion And Volumetric Kinetics Of Head And Neck Cancer Magnetic Resonance On A 15 T Mr-Linear Accelerator Hybrid System: A Prospective R-Ideal Stage 2a Imaging Biomarker Characterization/Pre-Qualification Study, Joint Head And Neck Radiation Therapy-Mri Development Cooperative, Mr-Linac Consortium Head And Neck Tumor Site Group

Faculty, Staff and Student Publications

OBJECTIVES: We aim to characterize the serial quantitative apparent diffusion coefficient (ADC) changes of the target disease volume using diffusion-weighted imaging (DWI) acquired weekly during radiation therapy (RT) on a 1.5 T MR-Linac and correlate these changes with tumor response and oncologic outcomes for head and neck squamous cell carcinoma (HNSCC) patients as part of a programmatic R-IDEAL biomarker characterization effort.

METHODS: Thirty patients with HNSCC who received curative-intent RT at MD Anderson Cancer Center, were included. Baseline and weekly MRI were obtained, and various ADC parameters were extracted from the regions of interest (ROIs). Baseline and weekly ADC parameters …

Going Circular: History, Present, And Future Of Circrnas In Cancer, Giuseppina Pisignano, David C Michael, Tanvi H Visal, Radu Pirlog, Michael Ladomery, George A Calin

Faculty, Staff and Student Publications

To date, thousands of highly abundant and conserved single-stranded RNA molecules shaped into ring structures (circRNAs) have been identified. CircRNAs are multifunctional molecules that have been shown to regulate gene expression transcriptionally and post-transcriptionally and exhibit distinct tissue- and development-specific expression patterns associated with a variety of normal and disease conditions, including cancer pathogenesis. Over the past years, due to their intrinsic stability and resistance to ribonucleases, particular attention has been drawn to their use as reliable diagnostic and prognostic biomarkers in cancer diagnosis, treatment, and prevention. However, there are some critical caveats to their utility in the clinic. Their …

Carm1 Arginine Methyltransferase As A Therapeutic Target For Cancer, Margarida Santos, Jee Won Hwang, Mark T Bedford

Faculty, Staff and Student Publications

Coactivator-associated arginine methyltransferase 1 (CARM1) is an arginine methyltransferase that posttranslationally modifies proteins that regulate multiple levels of RNA production and processing. Its substrates include histones, transcription factors, coregulators of transcription, and splicing factors. CARM1 is overexpressed in many different cancer types, and often promotes transcription factor programs that are co-opted as drivers of the transformed cell state, a process known as transcription factor addiction. Targeting these oncogenic transcription factor pathways is difficult but could be addressed by removing the activity of the key coactivators on which they rely. CARM1 is ubiquitously expressed, and its KO is less detrimental in …