Diseases Commons^™

Effect Of Quality Of Life On Radiation Adherence For Patients With Cervical Cancer In An Urban Safety Net Health System, Alison K Yoder, Elizabeth Dong, Xiaoman Yu, Alfredo Echeverria, Shelly Sharma, Jane Montealegre, Michelle S Ludwig

Faculty, Staff and Students Publications

PURPOSE: Outcomes for patients undergoing chemoradiation for cervical cancer are dependent on adherence to radiation therapy (RT). In other diseases, quality of life (QoL) is associated with treatment adherence, but the association between QoL and RT adherence for patients with cervical cancer remains unclear.

METHODS AND MATERIALS: This prospective study included patients undergoing RT for cervical cancer from 2017 to 2021 at an urban safety net hospital. The Functional Assessment of Cancer Therapy-Cervical Cancer Version 4 was used to assess QoL based on 5 subscales (physical, functional, social and emotional, and cervical-cancer specific). The survey was administered at radiation consult, …

Neighborhood-Level Factors Contribute To Disparities In Hepatocellular Carcinoma Incidence In Texas, Abiodun O Oluyomi, Hashem B El-Serag, Adegboyega Olayode, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Texas has the highest hepatocellular carcinoma (HCC) incidence rates in the continental United States, but these rates vary by race-ethnicity. We examined racial-ethnic disparities through a geospatial analysis of the social determinants of health.

METHODS: Using data from the Texas Cancer Registry, we assembled 11,547 HCC cases diagnosed between 2011 and 2015 into Texas's census tracts geographic units. Twenty-nine neighborhood measures representing demographics and socioeconomic, and employment domains were retrieved from the U.S. Census Bureau. We performed a series of aspatial and spatially weighted regression models to identify neighborhood-level characteristics associated with HCC risk.

RESULTS: We found …

Effect Of Quality Of Life On Radiation Adherence For Patients With Cervical Cancer In An Urban Safety Net Health System, Alison K Yoder, Elizabeth Dong, Xiaoman Yu, Alfredo Echeverria, Shelly Sharma, Jane Montealegre, Michelle S Ludwig

Faculty, Staff and Students Publications

PURPOSE: Outcomes for patients undergoing chemoradiation for cervical cancer are dependent on adherence to radiation therapy (RT). In other diseases, quality of life (QoL) is associated with treatment adherence, but the association between QoL and RT adherence for patients with cervical cancer remains unclear.

METHODS AND MATERIALS: This prospective study included patients undergoing RT for cervical cancer from 2017 to 2021 at an urban safety net hospital. The Functional Assessment of Cancer Therapy-Cervical Cancer Version 4 was used to assess QoL based on 5 subscales (physical, functional, social and emotional, and cervical-cancer specific). The survey was administered at radiation consult, …

Comparison Of Neurocognitive And Quality-Of-Life Outcomes In Pediatric Craniopharyngioma Patients Treated With Partial Resection And Radiotherapy Versus Gross-Total Resection Only, Guillermo Aldave, M Fatih Okcu, Murali Chintagumpala, Lucia Ruggieri, Charles G Minard, Fatema Malbari, Lisa E Mash, Arnold C Paulino, Susan Mcgovern, Uma Ramaswamy, William Whitehead, Lisa S Kahalley

Faculty, Staff and Students Publications

OBJECTIVE: The optimal management of pediatric craniopharyngioma patients remains controversial, shifting from radical resection (gross-total resection [GTR]) to a more conservative approach with partial resection/biopsy followed by radiotherapy (PR+RT). To the authors' knowledge, no previous studies have compared neurocognitive and quality-of-life (QOL) outcomes between the two main treatments. In this study, the authors compared changes in intellectual, adaptive, and QOL scores in children treated for craniopharyngioma with GTR and those treated with PR+RT.

METHODS: Patients underwent annual neurocognitive and QOL evaluations for up to 10 years posttreatment, including the Full-Scale IQ, Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), Working …

The Prevalence And Determinants Of Nafld And Mafld And Their Severity In The Va Primary Care Setting, Aaron P Thrift, Theresa H Nguyen, Codey Pham, Maya Balakrishnan, Fasiha Kanwal, Rohit Loomba, Hao T Duong, David Ramsey, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: A recent panel of international experts proposed the disease acronym metabolic (dysfunction)-associated fatty liver disease (MAFLD) in lieu of nonalcoholic fatty liver disease (NAFLD). We aimed to estimate the burden of and risk factors for NAFLD and MAFLD, and to examine the concordance between definitions in a Veterans population.

METHODS: We conducted a cross-sectional study among randomly selected patients within primary care at the Houston Veterans Affairs (VA) facility. Participants completed a survey, provided blood, and underwent Fibroscan. In the absence of heavy alcohol, hepatitis C virus and hepatitis B virus, a controlled attenuation parameter median ≥290 …

The Predictive Impact Of Dual Somatostatin Receptor/Fluorodeoxyglucose (Fdg) Positron Emission Tomography (Pet) In Metastatic Gastroenteropancreatic Neuroendocrine Tumors (Gep-Nets): Review Of Literature And A Single Institution Experience, Amr Mohamed, Sylvia L Asa, Zhenghong Lee, Sree H Tirumani, Qiubai Li, Norbert Avril, David Bajor, Amit Mahipal, Sakti Chakrabarti, J Eva Selfridge, Arash Kardan

Faculty, Staff and Students Publications

Treatment with radiolabelled somatostatin analogs, a form of peptide receptor radionuclide therapy (PRRT), has changed the management of patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). There is a subgroup of patients who have suboptimal benefit and rapidly progress on PRRT, indicating that accurate prognostic and predictive markers are urgently needed. Currently, most of the literature concentrate on the prognostic impact of the dual positron emission tomography (PET) scan with very few information regarding the predictive value. We report a case series and review the literature to summarizes the predictive value of combined somatostatin receptor (SSTR) and fluorodeoxyglucose (FDG) PET in …

Head And Neck Tumor Histopathological Image Representation With Pre- Trained Convolutional Neural Network And Vision Transformer, Ranny Rahaningrum Herdiantoputri, Daisuke Komura, Tohru Ikeda, Shumpei Ishikawa

Journal of Dentistry Indonesia

Image representation via machine learning is an approach to quantitatively represent histopathological images of head and neck tumors for future applications of artificial intelligence-assisted pathological diagnosis systems. Objective: This study compares image representations produced by a pre-trained convolutional neural network (VGG16) to those produced by a vision transformer (ViT-L/14) in terms of the classification performance of head and neck tumors. Methods: W hole-slide images of five oral t umor categories (n = 319 cases) were analyzed. Image patches were created from manually annotated regions at 4096, 2048, and 1024 pixels and rescaled to 256 pixels. Image representations were …

A Precision Environmental Health Approach To Prevention Of Human Disease, Andrea Baccarelli, Dana C Dolinoy, Cheryl Lyn Walker

Faculty, Staff and Students Publications

Human health is determined by the interaction of our environment with the genome, epigenome, and microbiome, which shape the transcriptomic, proteomic, and metabolomic landscape of cells and tissues. Precision environmental health is an emerging field leveraging environmental and system-level ('omic) data to understand underlying environmental causes of disease, identify biomarkers of exposure and response, and develop new prevention and intervention strategies. In this article we provide real-life illustrations of the utility of precision environmental health approaches, identify current challenges in the field, and outline new opportunities to promote health through a precision environmental health framework.

Increased Breast And Colorectal Cancer Risk In Type 2 Diabetes: Awareness Among Adults With And Without Diabetes And Information Provision On Diabetes Websites, Laura Ashley, Kathryn A Robb, Daryl B O'Connor, Rebecca Platt, Mollie Price, Olivia Robinson, Elizabeth Travis, Lorraine Lipscombe, Ramzi Ajjan, Rebecca Birch

Faculty, Staff and Student Publications

BACKGROUND: People with type 2 diabetes mellitus (T2DM) have a higher risk of developing breast and bowel cancers but are less likely to participate in cancer screening.

PURPOSE: Two interlinked studies examined public awareness of the fact that T2DM increases breast and bowel cancer risk, and provision of this information on diabetes websites.

METHODS: Study-1: phase-1 surveyed awareness of T2DM-increased cancer risk in a nationally-representative British sample aged 50-74 (N = 1,458) and compared respondents with and without T2DM (n = 125 vs. n = 1,305); phase-2 surveyed an additional exclusively T2DM sample (N = 319). Study-2: High-ranking diabetes websites …

Perspectives Of People With Cancer Or Hereditary Cancer Risk On The Use And Value Of Online Peer Support, Jill Holdren, Karl Surkan, Andrea Downing

Journal of Patient-Centered Research and Reviews

Purpose: People with cancer routinely seek information and support in peer groups online. While peer communities constitute a major component of the health care landscape, they exist in isolation from clinical and research institutions. This study aimed to explore how and why cancer patients utilize online peer support groups and how they might be improved.

Methods: A convenience sample of members of 6 closed Facebook cancer peer support groups (n = 291) participated in an online needs assessment survey. We further conducted semi-structured interviews with 14 members and 6 moderator-patients, hand-coding the free-text responses and interview transcripts.

Results: Group …

The "Great Debate" At Melanoma Bridge 2022, Naples, December 1st-3rd, 2022, Paolo A Ascierto, Christian Blank, Alexander M Eggermont, Claus Garbe, Jeffrey E Gershenwald, Omid Hamid, Axel Hauschild, Jason J Luke, Janice M Mehnert, Jeffrey A Sosman, Hussein A Tawbi, Mario Mandalà, Alessandro Testori, Corrado Caracò, Iman Osman, Igor Puzanov

Faculty, Staff and Student Publications

The Great Debate session at the 2022 Melanoma Bridge congress (December 1-3) featured counterpoint views from leading experts on five contemporary topics of debate in the management of melanoma. The debates considered the choice of anti-lymphocyte-activation gene (LAG)-3 therapy or ipilimumab in combination with anti-programmed death (PD)-1 therapy, whether anti-PD-1 monotherapy is still acceptable as a comparator arm in clinical trials, whether adjuvant treatment of melanoma is still a useful treatment option, the role of adjuvant therapy in stage II melanoma, what role surgery will continue to have in the treatment of melanoma. As is customary in the Melanoma Bridge …

Interrogating Bromodomain Inhibitor Resistance In Kmt2a-Rearranged Leukemia Through Combinatorial Crispr Screens, Shaela Wright, Jianzhong Hu, Hong Wang, Judith Hyle, Yang Zhang, Guoqing Du, Marina Y Konopleva, Steven M Kornblau, Mohamed Nadhir Djekidel, Wojciech Rosikiewicz, Beisi Xu, Rui Lu, Jun J Yang, Chunliang Li

Faculty, Staff and Student Publications

Bromo- and extra-terminal domain inhibitors (BETi) have exhibited therapeutic activities in many cancers. However, the mechanisms controlling BETi response and resistance are not well understood. We conducted genome-wide loss-of-function CRISPR screens using BETi-treated KMT2A-rearranged (KMT2A-r) cell lines. We revealed that Speckle-type POZ protein (SPOP) gene (Speckle Type BTB/POZ Protein) deficiency caused significant BETi resistance, which was further validated in cell lines and xenograft models. Proteomics analysis and a kinase-vulnerability CRISPR screen indicated that cells treated with BETi are sensitive to GSK3 perturbation. Pharmaceutical inhibition of GSK3 reversed the BETi-resistance phenotype. Based on this observation, a combination therapy regimen inhibiting both …

Association Of Suppressive Myeloid Cell Enrichment With Aggressive Oropharynx Squamous Cell Carcinoma, Changlin Yang, Rekha Garg, Kristanna Fredenburg, Frances Weidert, Hector Mendez-Gomez, Robert Amdur, Ji-Hyun Lee, Jamie Ku, Jesse Kresak, Stephanie Staras, Andrew G Sikora, Lily Wang, Daniel Mcgrail, Duane Mitchell, Elias Sayour, Natalie Silver

Faculty, Staff and Student Publications

BACKGROUND: While immune-cell infiltrated tumors, such as human papillomavirus positive (HPV+) ororpharyngeal squamous cell carcinomas (OPSCC) have been associated with an improved clinical prognosis, there is evidence to suggest that OPSCCs are also subjected to increased immunoregulatory influence. The objective of this study was to assess whether patients with clinically aggressive OPSCC have a distinct immunosuppressive immune signature in the primary tumor.

METHODS: This retrospective case-control study analyzed 37 pre-treatment tissue samples from HPV+ and HPV-negative OPSCC patients treated at a single institution. The cases were patients with known disease recurrence and the controls were patients without disease recurrence. An …

Symptom Management Care Pathway Adaptation Process And Specific Adaptation Decisions, Emily Vettese, Farha Sherani, Allison A. King, Lolie Yu, Catherine Aftandilian, Christina Baggott, Vibhuti Agarwal, Ramamoorthy Nagasubramanian, Kara M. Kelly, David R. Freyer, Etan Orgel, Scott M. Bradfield, Wade Kyono, Michael Roth, Lisa M. Klesges, Melissa Beauchemin, Allison Grimes, George Tomlinson, L. Lee Dupuis, Lillian Sung

School of Medicine Faculty Publications

BACKGROUND: There is substantial heterogeneity in symptom management provided to pediatric patients with cancer. The primary objective was to describe the adaptation process and specific adaptation decisions related to symptom management care pathways based on clinical practice guidelines. The secondary objective evaluated if institutional factors were associated with adaptation decisions. METHODS: Fourteen previously developed symptom management care pathway templates were reviewed by an institutional adaptation team composed of two clinicians at each of 10 institutions. They worked through each statement for all care pathway templates sequentially. The institutional adaptation team made the decision to adopt, adapt or reject each statement, …

Cancer Cell-Extrinsic Roles For The Androgen Receptor In Prostate Cancer, Andrew W Hahn, Bilal A Siddiqui, Javier Leo, Eleonora Dondossola, Kaitlin J Basham, Cindy K Miranti, Daniel E Frigo

Faculty, Staff and Student Publications

Given the central role of the androgen receptor (AR) in prostate cancer cell biology, AR-targeted therapies have been the backbone of prostate cancer treatment for over 50 years. New data indicate that AR is expressed in additional cell types within the tumor microenvironment. Moreover, targeting AR for the treatment of prostate cancer has established side effects such as bone complications and an increased risk of developing cardiometabolic disease, indicating broader roles for AR. With the advent of novel technologies, such as single-cell approaches and advances in preclinical modeling, AR has been identified to have clinically significant functions in other cell …

Met Alterations Are Associated With Osimertinib Resistance In Egfr Mutant Lung Cancers, A Meta-Analysis, Annie Le, Marissa Viola, Jun Wang

Research Day

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) that has been used to treat EGFR mutant lung cancers, especially those with EGFR T790M mutation. Resistance to osimertinib is likely associated with acquired genetic alterations in these cancer cells. Mesenchymal epithelial transition (MET) is a tyrosine kinase and its amplification is frequently seen in osimertinib resistant patients. To investigate whether the presence of MET alteration is associated with osimertinib resistance, a meta-analysis was conducted using published observations of EGFR mutant lung cancer patients treated with osimertinib. Frequencies of MET alterations are variable, ranging from 0-43% in osimertinib resistant patients. MET alteration …

Serinc5 Restricts Hiv Membrane Fusion By Altering Lipid Order And Heterogeneity In The Viral Membrane, Amanda E Ward, Daria Sokovikova, Melvin Neal Waxham, Frederick A Heberle, Ilya Levental, Kandice R Levental, Volker Kiessling, Judith M White, Lukas K Tamm

Faculty, Staff and Student Publications

The host restriction factor, Serinc5, incorporates into budding HIV particles and inhibits their infection by an incompletely understood mechanism. We have previously reported that Serinc5 but not its paralogue, Serinc2, blocks HIV cell entry by membrane fusion, specifically by inhibiting fusion pore formation and dilation. A body of work suggests that Serinc5 may alter the conformation and clustering of the HIV fusion protein, Env. To contribute an additional perspective to the developing model of Serinc5 restriction, we assessed Serinc2 and Serinc5's effects on HIV pseudoviral membranes. By measuring pseudoviral membrane thickness via cryo-electron microscopy and order via the fluorescent dye, …

Pertuzumab, Trastuzumab, And An Aromatase Inhibitor For Her2-Positive And Hormone Receptor-Positive Metastatic Or Locally Advanced Breast Cancer: Pertain Final Analysis, Grazia Arpino, Juan De La Haba Rodríguez, Jean-Marc Ferrero, Sabino De Placido, C Kent Osborne, Dirk Klingbiel, Valentine Revelant, Christine Wohlfarth, Raf Poppe, Mothaffar F Rimawi

Faculty, Staff and Students Publications

PURPOSE: In PERTAIN's primary analysis (31 months' median follow-up), adding pertuzumab to trastuzumab and an aromatase inhibitor (AI) with/without chemotherapy significantly improved progression-free survival (PFS) in patients with previously untreated HER2-positive and hormone receptor-positive metastatic or locally advanced breast cancer (M/LABC). A potentially enhanced treatment effect was observed in patients with no induction chemotherapy. We present the final analysis (>6 years' median follow-up).

PATIENTS AND METHODS: Patients (N = 258) were randomized 1:1 to pertuzumab (loading/maintenance: 840/420 mg) plus trastuzumab (loading/maintenance: 8/6 mg/kg) every 3 weeks and an AI (1 mg anastrozole or 2.5 mg letrozole daily; Arm A), …

Mechanisms Of Response And Resistance To Combined Decitabine And Ipilimumab For Advanced Myeloid Disease, Livius Penter, Yang Liu, Jacquelyn O Wolff, Lin Yang, Len Taing, Aashna Jhaveri, Jackson Southard, Manishkumar Patel, Nicole M Cullen, Kathleen L Pfaff, Nicoletta Cieri, Giacomo Oliveira, Seunghee Kim-Schulze, Srinika Ranasinghe, Rebecca Leonard, Taylor Robertson, Elizabeth A Morgan, Helen X Chen, Minkyung H Song, Magdalena Thurin, Shuqiang Li, Scott J Rodig, Carrie Cibulskis, Stacey Gabriel, Pavan Bachireddy, Jerome Ritz, Howard Streicher, Donna S Neuberg, F Stephen Hodi, Matthew S Davids, Sacha Gnjatic, Kenneth J Livak, Jennifer Altreuter, Franziska Michor, Robert J Soiffer, Jacqueline S Garcia, Catherine J Wu

Faculty, Staff and Student Publications

The challenge of eradicating leukemia in patients with acute myelogenous leukemia (AML) after initial cytoreduction has motivated modern efforts to combine synergistic active modalities including immunotherapy. Recently, the ETCTN/CTEP 10026 study tested the combination of the DNA methyltransferase inhibitor decitabine together with the immune checkpoint inhibitor ipilimumab for AML/myelodysplastic syndrome (MDS) either after allogeneic hematopoietic stem cell transplantation (HSCT) or in the HSCT-naïve setting. Integrative transcriptome-based analysis of 304 961 individual marrow-infiltrating cells for 18 of 48 subjects treated on study revealed the strong association of response with a high baseline ratio of T to AML cells. Clinical responses were …

Targeting Of Epigenetic Co-Dependencies Enhances Anti-Aml Efficacy Of Menin Inhibitor In Aml With Mll1-R Or Mutant Npm1, Warren Fiskus, Christopher P Mill, Christine Birdwell, John A Davis, Kaberi Das, Steffen Boettcher, Tapan M Kadia, Courtney D Dinardo, Koichi Takahashi, Sanam Loghavi, Michael J Soth, Tim Heffernan, Gerard M Mcgeehan, Xinjia Ruan, Xiaoping Su, Christopher R Vakoc, Naval Daver, Kapil N Bhalla

Faculty, Staff and Student Publications

Monotherapy with Menin inhibitor (MI), e.g., SNDX-5613, induces clinical remissions in patients with relapsed/refractory AML harboring MLL1-r or mtNPM1, but most patients either fail to respond or eventually relapse. Utilizing single-cell RNA-Seq, ChiP-Seq, ATAC-Seq, RNA-Seq, RPPA, and mass cytometry (CyTOF) analyses, present pre-clinical studies elucidate gene-expression correlates of MI efficacy in AML cells harboring MLL1-r or mtNPM1. Notably, MI-mediated genome-wide, concordant, log2 fold-perturbations in ATAC-Seq and RNA-Seq peaks were observed at the loci of MLL-FP target genes, with upregulation of mRNAs associated with AML differentiation. MI treatment also reduced the number of AML cells expressing the stem/progenitor cell signature. A …

Molecular Mechanisms Of Ferroptosis And Updates Of Ferroptosis Studies In Cancers And Leukemia, Hiroki Akiyama, Bing Z Carter, Michael Andreeff, Jo Ishizawa

Faculty, Staff and Student Publications

Ferroptosis is a mode of cell death regulated by iron-dependent lipid peroxidation. Growing evidence suggests ferroptosis induction as a novel anti-cancer modality that could potentially overcome therapy resistance in cancers. The molecular mechanisms involved in the regulation of ferroptosis are complex and highly dependent on context. Therefore, a comprehensive understanding of its execution and protection machinery in each tumor type is necessary for the implementation of this unique cell death mode to target individual cancers. Since most of the current evidence for ferroptosis regulation mechanisms is based on solid cancer studies, the knowledge of ferroptosis with regard to leukemia is …

Clustering Of Pediatric Brain Tumors In Texas, 2000-2017, Thanh T Hoang, Omar Rosales, Elyse Burgess, Philip J Lupo, Michael E Scheurer, Abiodun O Oluyomi

Faculty, Staff and Students Publications

Risk factors for pediatric brain tumors are largely unknown. Identifying spatial clusters of these rare tumors on the basis of residential address may provide insights into childhood socio-environmental factors that increase susceptibility. From 2000-2017, the Texas Cancer Registry recorded 4305 primary brain tumors diagnosed among children (≤19 years old). We performed a spatial analysis in SaTScan to identify neighborhoods (census tracts) where the observed number of pediatric brain tumors was higher than expected. Within each census tract, the number of pediatric brain tumors was summed on the basis of residential address at diagnosis. The population estimate from the 2007-2011 American …

Upregulation Of Cell Surface Glycoproteins In Correlation With Kshv Lana In The Kaposi Sarcoma Tumor Microenvironment, Sara R. Privatt, Owen Ngalamika, Jianshui Zhang, Qinsheng Li, Charles Wood, John T. West

School of Medicine Faculty Publications

HIV-associated epidemic Kaposi sarcoma (EpKS) remains one of the most prevalent cancers in sub-Saharan Africa despite the widespread uptake of anti-retroviral therapy and HIV-1 suppression. In an effort to define potential therapeutic targets against KS tumors, we analyzed previously published KS bulk tumor transcriptomics to identify cell surface biomarkers. In addition to upregulated gene expression (>6-fold) in the EpKS tumor microenvironment, biomarkers were selected for correlation with KSHV latency-associated nuclear antigen (LANA) expression. The cell surface glycoprotein genes identified were KDR, FLT4, ADAM12, UNC5A, ZP2, and OX40, as well as the endothelial lineage determinants Prox-1 and CD34. Each protein …

A Distinct Pattern Of Growth And Rac1 Signaling In Melanoma Brain Metastasis Cells, Ioana Stejerean-Todoran, Phyllis A Gimotty, Andrea Watters, Patricia Brafford, Clemens Krepler, Tetiana Godok, Haiyin Li, Zuriñe Bonilla Del Rio, Anke Zieseniss, Dörthe M Katschinski, Sinem M Sertel, Silvio O Rizzoli, Bradley Garman, Katherine L Nathanson, Xiaowei Xu, Qing Chen, Jack H Oswald, Michal Lotem, Gordon B Mills, Michael A Davies, Michael P Schön, Ivan Bogeski, Meenhard Herlyn, Adina Vultur

Faculty, Staff and Student Publications

Background: Melanoma, the deadliest of skin cancers, has a high propensity to form brain metastases that are associated with a markedly worsened prognosis. In spite of recent therapeutic advances, melanoma brain lesions remain a clinical challenge, biomarkers predicting brain dissemination are not clear and differences with other metastatic sites are poorly understood.

Methods: We examined a genetically diverse panel of human-derived melanoma brain metastasis (MBM) and extracranial cell lines using targeted sequencing, a Reverse Phase Protein Array, protein expression analyses, and functional studies in vitro and in vivo.

Results: Brain-specific genetic alterations were not detected; however, MBM cells in vitro …

Brain Metastases From Biliary Tract Cancer: Case Series And Clinicogenomic Analysis, Grace N Dodoo, Brian De, Sunyoung S Lee, Joseph Abi Jaoude, Jean-Nicolas Vauthey, Ching-Wei D Tzeng, Hop S Tran Cao, Kalman A Katlowitz, Jacob J Mandel, Thomas H Beckham, Bruce D Minsky, Grace L Smith, Emma B Holliday, Albert C Koong, Prajnan Das, Cullen M Taniguchi, Milind Javle, Eugene J Koay, Ethan B Ludmir

Faculty, Staff and Student Publications

BACKGROUND: Limited data from small series have suggested that brain metastases from biliary tract cancers (BrM-BTC) affect ≤2% of patients with BTC. We sought to review our experience with patients with BrM-BTC and to identify associations of tumor-related molecular alterations with outcomes.

MATERIALS AND METHODS: A retrospective review of patients with BTC seen at a tertiary referral center from 2005 to 2021 was performed; patients with BrM-BTC were identified, and clinical and molecular data were collected.

RESULTS: Twenty-one of 823 patients with BTC (2.6%) developed BrM. For patients with BrM-BTC, median follow-up time was 27.9 months after primary BTC diagnosis …

Swi/Snf Blockade Disrupts Pu1-Directed Enhancer Programs In Normal Hematopoietic Cells And Acute Myeloid Leukemia, Courtney Chambers, Katerina Cermakova, Yuen San Chan, Kristen Kurtz, Katharina Wohlan, Andrew Henry Lewis, Christiana Wang, Anh Pham, Milan Dejmek, Michal Sala, Mario Loeza Cabrera, Rogelio Aguilar, Radim Nencka, H Daniel Lacorazza, Rachel E Rau, H Courtney Hodges

Faculty, Staff and Students Publications

UNLABELLED: In acute myeloid leukemia (AML), SWI/SNF chromatin remodeling complexes sustain leukemic identity by driving high levels of MYC. Previous studies have implicated the hematopoietic transcription factor PU.1 (SPI1) as an important target of SWI/SNF inhibition, but PU.1 is widely regarded to have pioneer-like activity. As a result, many questions have remained regarding the interplay between PU.1 and SWI/SNF in AML as well as normal hematopoiesis. Here we found that PU.1 binds to most of its targets in a SWI/SNF-independent manner and recruits SWI/SNF to promote accessibility for other AML core regulatory factors, including RUNX1, LMO2, and MEIS1. SWI/SNF inhibition …

The Association Between Caffeine Intake And The Colonic Mucosa-Associated Gut Microbiota In Humans-A Preliminary Investigation, Annie Dai, Kristi Hoffman, Anthony A Xu, Shawn Gurwara, Donna L White, Fasiha Kanwal, Albert Jang, Hashem B El-Serag, Joseph F Petrosino, Li Jiao

Faculty, Staff and Students Publications

We examined the association between caffeine and coffee intake and the community composition and structure of colonic microbiota. A total of 34 polyp-free adults donated 97 colonic biopsies. Microbial DNA was sequenced for the 16S rRNA gene V4 region. The amplicon sequence variant was assigned using DADA2 and SILVA. Food consumption was ascertained using a food frequency questionnaire. We compared the relative abundance of taxonomies by low (<82.9 mg) vs. high (≥82.9 mg) caffeine intake and by never or <2 cups vs. 2 cups vs. ≥3 cups coffee intake. False discovery rate-adjusted p values (q values) <0.05 indicated statistical significance. Multivariable negative binomial regression models were used to estimate the incidence rate ratio and its 95% confidence interval of having a non-zero count of certain bacteria by intake level. Higher caffeine and coffee intake was related to higher alpha diversity (Shannon index p < 0.001), higher relative abundance of Faecalibacterium and Alistipes, and lower relative abundance of Erysipelatoclostridium (q values < 0.05). After adjustment of vitamin B2 in multivariate analysis, the significant inverse association between Erysipelatoclostridium count and caffeine intake remained statistically significant. Our preliminary study could not …

Concurrent Intrathecal And Intravenous Nivolumab In Leptomeningeal Disease: Phase 1 Trial Interim Results, Isabella C Glitza Oliva, Sherise D Ferguson, Roland Bassett, Alexandra P Foster, Ida John, Tarin D Hennegan, Michelle Rohlfs, Jessie Richard, Masood Iqbal, Tina Dett, Carol Lacey, Natalie Jackson, Theresa Rodgers, Suzanne Phillips, Sheila Duncan, Lauren Haydu, Ruitao Lin, Rodabe N Amaria, Michael K Wong, Adi Diab, Cassian Yee, Sapna P Patel, Jennifer L Mcquade, Grant M Fischer, Ian E Mccutcheon, Barbara J O'Brien, Sudhakar Tummala, Matthew Debnam, Nandita Guha-Thakurta, Jennifer A Wargo, Fernando C L Carapeto, Courtney W Hudgens, Jason T Huse, Michael T Tetzlaff, Elizabeth M Burton, Hussein A Tawbi, Michael A Davies

Faculty, Staff and Student Publications

There is a critical need for effective treatments for leptomeningeal disease (LMD). Here, we report the interim analysis results of an ongoing single-arm, first-in-human phase 1/1b study of concurrent intrathecal (IT) and intravenous (IV) nivolumab in patients with melanoma and LMD. The primary endpoints are determination of safety and the recommended IT nivolumab dose. The secondary endpoint is overall survival (OS). Patients are treated with IT nivolumab alone in cycle 1 and IV nivolumab is included in subsequent cycles. We treated 25 patients with metastatic melanoma using 5, 10, 20 and 50 mg of IT nivolumab. There were no dose-limiting …

Enoxaparin May Be Associated With Lower Rates Of Mortality Than Unfractionated Heparin In Neurocritical And Surgical Patients, Sophie Samuel, Catherine To, Yaobin Ling, Kai Zhang, Xiaoqian Jiang, Elmer V Bernstam

Faculty, Staff and Student Publications

Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are often administered to prevent venous thromboembolism (VTE) in critically ill patients. However, the preferred prophylactic agent (UFH or LMWH) is not known. We compared the all-cause mortality rate in patients receiving UFH to LMWH for VTE prophylaxis. We conducted a retrospective propensity score adjusted analysis of patients admitted to neuro-critical, surgical, or medical intensive care units. Patients were included if they were screened with venous duplex ultrasonography or computed tomography angiography for detection of VTE. The primary outcome was all-cause mortality. Secondary outcomes included the prevalence of VTE, deep vein …

In Vitro Activity Of Eravacycline And Comparator Agents Against Bacterial Pathogens Isolated From Patients With Cancer, Kenneth Rolston, Bahgat Gerges, Lior Nesher, Samuel A Shelburne, Randall Prince, Issam Raad

Faculty, Staff and Student Publications

BACKGROUND: Bacterial infections are common in patients with cancer, and many bacteria have developed resistance to currently used antibiotics.

OBJECTIVES: We evaluated the

METHODS: Antimicrobial susceptibility testing was performed using CLSI-approved methodology and interpretive criteria for 255 Gram-positive and 310 Gram-negative bacteria. MIC and susceptibility percentage were calculated according to CLSI and FDA breakpoints when available.

RESULTS: Eravacycline had potent activity against most Gram-positive bacteria, including MRSA. Of 80 Gram-positive isolates with available breakpoints, 74 (92.5%) were susceptible to eravacycline. Eravacycline had potent activity against most Enterobacterales, including ESBL-producing organisms. Of 230 Gram-negative isolates with available breakpoints, 201 (87.4%) were …