Digital Commons Network^™

External Validation Of The Proliferation Saturation Index Model In Predicting Tumour Volume Regression In Patients With Non-Small Cell Lung Cancer Undergoing Radiation Therapy, Sarah Barrett, Mohammad Zahid, Conor K Mcgarry, Heiko Enderling, Gerard M Walls, Laure Marignol

Faculty, Staff and Student Publications

Background: The Proliferation Saturation Index (PSI) model is a patient-specific mathematical model designed to simulate and predict tumour volume regression (TVR) during radiation therapy (RT) using early treatment response dynamics. This study validates the PSI model in an independent external cohort of patients with non-small cell lung cancer (NSCLC) using previously derived model parameters.

Methods: In a cohort of 71 patients, treated with definitive RT alone (55Gy/20#) tumour volume measurements extracted from 6 Cone Beam CT (CBCT) scans acquired on days 1, 2 and 3 and weekly thereafter. Model predictions of TVR at final CBCT (CBCT6) were made using tumour …

Hp1Β Recruits Ring1a To Ubiquitinate Histone H2a For Brca1-Mediated Resection Of Double-Stand Breaks, Vijaya Charaka, Raj K Pandita, Chi-Lin Tsai, Xiaoyan Wang, Sharmista Chakraborty, Kenneth S Ramos, Sandhik Nandi, Fransisca Leonard, Vipin Singh, Partha S Sarkar, Clayton R Hunt, John A Tainer, Chandrima Das, Tej K Pandita

Faculty, Staff and Student Publications

Efficient DNA double-strand break (DSB) repair by homologous recombination (HR), as initiated by BRCA1 recruitment orchestrated by histone and non-histone proteins, is critical to genome stability, replication, transcription, and cancer avoidance. Here we reveal Heterochromatin Protein1 beta (HP1β) promotes BRCA1 enrichment at DNA DSB sites in gene-rich regions, and this is impaired by HP1β depletion. We find that HP1β is specifically enriched at DSBs within gene-rich regions via its Chromo Shadow Domain (CSD) that interacts with both Chromatin Assembly Factor 1 and the RING1A ubiquitinase component of Polycomb Repressor Complex 1. The resulting protein complex facilitates BRCA1 recruitment by promoting …

Nci9673 (Part B): Etctn Randomized Phase Ii Study Of Nivolumab With Or Without Ipilimumab In Refractory, Metastatic Squamous Cell Carcinoma Of The Anal Canal, Van K Morris, Kristen K Ciombor, Lianchun Xiao, Joshua K Ochieng, Enrica Marmonti, Blase Polite, Benjamin A Weinberg, John C Krauss, John Hays, Sarbajit Mukherjee, Olivia Aranha, Syma Iqbal, Tony Shields, Al B Benson, Syed Kazmi, Christopher Lieu, Howard Hochster, Jennifer Whisenant, Cara Haymaker, Cathy Eng

Faculty, Staff and Student Publications

Purpose: In the previously completed NCI9673 (part A) single-arm study, the antiprogrammed death (PD)-ligand-1 antibody nivolumab demonstrated efficacy for patients with metastatic anal cancer. In NCI9673 (Part B), we evaluated the anticytotoxic T-cell lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in combination with nivolumab for patients with incurable anal cancer.

Methods: In this phase II NCI ETCTN trial, 100 patients with refractory, incurable anal cancer were randomly assigned to receive nivolumab (480 mg IV once every 4 weeks) alone or with ipilimumab (1 mg/kg IV once every 8 weeks). The primary end point was progression-free survival (PFS). Secondary endpoints included radiographic response, …

Renin-Angiotensin-Aldosterone System In Preeclampsia: Pathophysiological Insights And Links To Vascular Dementia, Robin C. Finch, Jenny Lutshumba, Elizabeth Mirsky, Esther Ndashaala, Kelsey Bullens, Emma Smith

Pediatrics Faculty Publications

Pre-eclampsia, a condition characterized by new-onset hypertension during pregnancy and one or more indices of organ damage, is a major driver of both short and long-term maternal health outcomes. Individuals with a history of pre-eclampsia are at increased risk for cardiovascular, renal, and other chronic diseases. Recent studies have linked pre-eclampsia history with increased risk of dementia later in life, underscoring the importance of new guidelines emphasizing blood pressure control to reduce the risk of cognitive decline. Unfortunately, neither mechanisms underlying causes of pre-eclampsia nor their links with cognitive function are well understood. Vascular contributions to cognitive impairment and dementia …

Adipocyte-Specific Deletion Of Sine Oculis Homeobox Homolog 1 Inhibits Lipolysis And Reduces Skin Fibrosis, Nancy Wareing, Tingting W Mills, Scott Collum, Minghua Wu, Lucy Revercomb, René Girard, Hui Liu, Alexes Daquinag, Mikhail Kolonin, Marka Lyons, Brian Skaug, Weizhen Bi, Meer A Ali, Haniyeh Koochak, Anthony R Flores, Yuntao Yang, W Jim Zheng, William R Swindell, Shervin Assassi, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Dermal fibrosis is a cardinal feature of systemic sclerosis (SSc) for which there are limited Systemic sclerosis (SSc) is characterized by dermal fibrosis accompanied by loss of dermal white adipose tissue (DWAT), yet the mechanisms linking adipocyte depletion to fibroblast activation remain unclear. Here we identify the transcription factor SIX1 as a central regulator coupling adipogenic repression with profibrotic signaling. SIX1 expression was increased in skin biopsies from two independent SSc cohorts and localized to fibroblast and perivascular stromal cells. In mice, ubiquitous or adipocyte-specific deletion of Six1 preserved DWAT, reduced collagen accumulation, and selectively decreased pro-fibrotic mediators. In cultured …

Cml-Like Biology Is A Unifying Feature Of Myeloid/Lymphoid Neoplasms With Tyrosine Kinase Fusions In Lymphoid Blast Phase Comment On: Multilineage Involvement In Abl-Class Fusion-Positive Pediatric B-Cell Acute Lymphoblastic Leukemia: Cml-Like Biology, Wei J Wang, Shimin Hu

Faculty, Staff and Student Publications

No abstract provided.

Sex-Specific Differences In Mediobasal Hypothalamus In Response To Nutritional States, Jonathan C Bean, Jinjing Jian, Tzu-Chiao Lu, Hailan Liu, Kristine Conde, Darah A Threat, Sanika V Jossy, Megan E Burt, Jingjing Cheng, Yue Deng, Xing Fang, Xiaoyu Geng, Junying Han, Yongxiang Li, Hesong Liu, Qingzhuo Liu, Yutian Liu, Yuhan Shi, Longlong Tu, Mengjie Wang, Xu Xu, Yuxue Yang, Meng Yu, Xinming Liu, Meixin Sun, Fuhui Wang, Olivia Z Ginnard, Yongjie Yang, Yang He, Chunmei Wang, Yanyan Qi, Hongjie Li, Yong Xu

Children’s Nutrition Research Center Staff Publications

The arcuate nucleus of the hypothalamus plays a central role in sensing and integrating nutritional, hormonal, and neural signals that regulate feeding, energy homeostasis, growth, and reproduction, all of which show pronounced sex differences. However, the cellular mechanisms underlying these responses remain poorly understood. We performed snRNA-seq of the mediobasal hypothalamus, focusing on the arcuate nucleus, in female and male mice under different nutritional states. Analysis of 42 cell types revealed that Agrp neurons were most sensitive to nutritional changes, dopaminergic neurons showed strong sex-specific differences, and KNDy neurons were highly responsive to both sex and nutrition. Pomc neurons displayed …

“From Compression To Closure: Efficacy And Safety Of Vascular Closure Devices (Vcd) Versus Manual Compression: A Comparative Analysis Of Hemostatic Strategies Of Obtura, Angioseal, And Proglide Vcd“, Praveen Shukla, Kumar Himanshu, Ali Mohammed, Mukesh Jitendra Jha, Santosh Kumar Sinha, Puneet Aggarwal, Mohammad Mahmodullah Razi, Mohit Sachan, Awadhesh Kumar Sharma, Umeshwar Pandey, Neeraj Prakash, Rakesh Kumar Verma

Journal of the Saudi Heart Association

Objective: Use of vascular closure devices (VCDs) for femoral artery puncture site hemostasis has increased but their safety and efficacy have remained unclear. This study was designed to compare safety and efficacy of Obtura, Angioseal, and Proglide VCD to manual compression (MC) and also between for femoral artery haemostasis.

Methods:This was prospective, randomized controlled study where patients were randomly assigned on 1:1:1:1 basis. Primary endpoints were time to hemostasis (TTH) and ambulation time (AT) while secondary endpoints were deployment success, device related adverse events and technical success rate. ANOVA and Tukey HSD was conducted to draw significant difference between …

Cancer Treatment Induced Skeletal Muscle Loss As A Predictor Of Late Cardiotoxicity In Aya: A Pilot Study, Savannah V. Rauschendorfer, Efstratios Koutroumpakis, Behrang Amini, Juhee Song, Michelle Hildebrandt, Anita Deswal Md Mph, J. Andrew Livingston, Michael Roth, Eugenie S. Kleinerman Md

Cancer Survivorship Research Retreat

No abstract provided.

A Scarring Experience: Pelvic Floor Rehabilitation As A Novel Palliative Approach In Colorectal Cancer Survivorship, Aryan Dowlatshahi, Leanne Jackson, Mary Garcia

Cancer Survivorship Research Retreat

This is a discussion of the novel approach of pelvic floor rehabilitation in its utility specifically for colorectal cancer survivorship which will be additionally presented at the MD Anderson Survivorship Research Retreat conference.

Osteopathic Manipulative Medicine As An Adjunctive Approach To Improve Pelvic Perfusion And Fertility-Related Physiologic Markers, Ashton Dodd, Yanielisse Bellinger, Marsha Chevalier, Annaliese Taylor, Jacob Warner-Palacio, Aurora Jeanes, Nathan Barnhurst

Annual Research Symposium

No abstract provided.

Propofol In Chronic Cannabis Users: A Mechanistic Link To Cannabinoid Hyperemesis?, Jonmark I. Dolendo, Sonia Frick, Jia Q. Yang, Brad A. Haubrich

Annual Research Symposium

Purpose: Cannabinoid hyperemesis syndrome (CHS) is characterized by cyclic nausea, vomiting, and abdominal pain in chronic cannabis users, often relieved by exposure to hot water. Propofol, a widely used GABAergic anesthetic with antiemetic properties, has paradoxically been implicated in exacerbating hyperemetic episodes in some cannabis users. With the growing legalization of marijuana and social acceptance to its recreational use it is believed that this phenomenon will be more ubiquitous to clinicians. This review aims to investigate the mechanistic and clinical evidence linking propofol administration to CHS and to summarize strategies for prevention, diagnosis, and management.

Methods: PubMed and EBSCO were …

Racing Against Time: Simultaneous Anterior And Inferior St-Elevation Myocardial Infarction Managed With The Nano-Crush Bifurcation Stenting Technique, Selim Süleyman Sert, Fatih Aksoy

Journal of the Saudi Heart Association

We present a rare case of simultaneous anterior and inferior ST-elevation myocardial infarction caused by the acute occlusion of both the right coronary artery and the left anterior descending artery. The culprit LAD lesion involved a true bifurcation, which was successfully treated using the nano-crush stenting technique, achieving complete reperfusion. This case highlights the feasibility of complex bifurcation intervention in a hemodynamically unstable patient with double-vessel STEMI. It underscores the importance of rapid diagnosis, aggressive revascularization, and appropriate stenting strategy in managing multivessel acute myocardial infarction.

Combination Lingual Compression And Maxillomandibular Fixation For Persistent Acquired Macroglossia: A Case Report, Emma De Ravin, Annie Moroco, Adam J. Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

No abstract provided.

Management Of Acute Myeloid Leukemia: A Review, Chetan Jeurkar, Lana King, David Baek, Lindsay Wilde, Gina Keiffer, Margaret Kasner

Kimmel Cancer Center Faculty Papers

Background/Objectives: Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with historically poor outcomes, particularly among older adults and patients harboring high-risk molecular features. Advances in genomic profiling have enabled the development of targeted therapies, reshaping treatment algorithms beyond conventional cytarabine-anthracycline induction and hypomethylating agent-based regimens. This review summarizes current evidence and emerging therapeutic strategies across four evolving areas: menin inhibition, FLT3 inhibition, IDH inhibition and treatment approaches for TP53-mutated AML. Methods: We reviewed published clinical trials, preclinical studies, and ongoing clinical trials evaluating targeted therapies in AML. Emphasis was placed on agents with regulatory approval or substantial clinical development, …

Comparative Safety, Efficacy, And Predictors Of Complete Occlusion Of Flow Diverter Devices In The Treatment Of Unruptured Distal Anterior Cerebral Artery Aneurysms, Hamza Adel Salim, Luca Scarcia, Frédéric Clarençon, Orabi Hajjeh, Motaz Daraghma, Davide Simonato, Yan-Lin Li, Eimad Shotar, Kevin Premat, Pascal Jabbour, Stavropoula Tjoumakaris, Michael R. Gooch, Marios Psychogios, Nikos Ntoulias, Peter Sporns, Ajit S. Puri, Jasmeet Singh, Anna Luisa Kuhn, Ameer E. Hassan, Oktay Algin, Markus A. Möhlenbruch, Sophia Hohenstatt, Riccardo Russo, Mauro Bergui, Oded Goren, Matthew J. Kole, Nourou Dine Adeniran Bankole, Richard Bibi, Gregoire Boulouis, Takeshi Morimoto, Fumihiro Sakakibara, Raoul Pop, Ciprian Juravle, Joanna W. K. Ho, Ãngel Ferrario, Virginia Pujol Lereis, Jared Cooper, Chirag D. Gandhi, Giancarlo Salsano, Lucio Castellan, Arturo Consoli, Alessandro Sgreccia, Eytan Raz, Charlotte Chung, Julien Burel, Chrysanthi Papagiannaki, Umair Rasheed, Khawaja Muhammad Baqir Hassan, Hong Tao, Zhe Ji, Riitta Rautio, Matias Sinisalo, Maria Ruggiero, Elvis Lafe, Valerio Da Ros, Luigi Bellini, Joseph Domenico Gabrieli, Francesco Causin, Michael R. Levitt, Kate Carroll, Zachary Abecassis, Antonio Armando Caragliano, Sergio Lucio Vinci, Guillaume Bellanger, Christophe Cognard, Gaultier Marnat, Lisa Saleille, Nicola Limbucci, Francesco Capasso, Mariangela Piano, Claudia Rollo, Alexis Guedon, Francesco Arpaia, Andrea Romi, Fortunato Di Caterino, Alessandra Biondi, Erwah Kalsoum, Mykola Vyval, Adrien Guenego, Than Nguyen, Mohamad Abdalkader, Thibault Agripnidis, Aman B. Patel, Vitor Mendes Pereira, Maurizio Fuschi, Alessandro Pedicelli, Vivek Yedavalli, Max Wintermark, Andrea M. Alexandre, Adam A. Dmytriw, Creta Investigators

Department of Neurosurgery Faculty Papers

BACKGROUND: Flow diverters (FDs) are increasingly used for cerebral aneurysms, including distal anterior cerebral artery (DACA) aneurysms, but comparative data between devices in this challenging location are limited.

OBJECTIVE: To compare the safety and efficacy of Pipeline, Silk Vista Baby (SVB), and FRED Jr. FDs for unruptured DACA aneurysms and identify predictors of complete occlusion.

METHODS: We retrospectively analyzed 166 patients treated with FDs at 39 centers in 14 countries (2018–2022) from the CRETA registry. Outcomes included aneurysm occlusion (O’Kelly–Marotta [OKM] scale), complications, retreatment, modified Rankin Scale (mRS) scores, and independent predictors of complete occlusion using multivariable Cox regression.

RESULTS: …

Anti-Apoptotic Bcl-2 Binds To All Three Ip3r Isoforms, Thereby Limiting The Ca2+-Flux Properties Of Ip3r Homo-Tetramers, Ian De Ridder, Claire Cauwelier, Larry E Wagner Ii, Jens Loncke, Vikas Arige, Irina I Serysheva, David I Yule, Geert Bultynck

Faculty, Staff and Student Publications

Anti-apoptotic B-cell lymphoma 2 (BCL-2) controls inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca²+ signalling. As cells typically express all three IP3R isoforms in variable abundances that assemble in hetero-tetrameric channels, the specific effects of BCL-2 on each isoform remain unclear. Here, we employed a reductionist approach using HEK293 cells triple-IP3R knockout reconstituted with a single IP3R isoform to elucidate the impact of BCL-2 on Ca2+ signalling by homo-tetrameric IP3R channels. Co-immunoprecipitation experiments demonstrated that BCL-2 interacts with each IP3R isoform. Live-cell Ca²+ imaging revealed that BCL-2 overexpression suppresses Ca²+ signals evoked by any of the three IP3R isoforms. Moreover, BCL-2 overexpression impaired …

Online Decision Support For Implementing Evidence-Based Hpv Vaccination Strategies In Texas Safety-Net Pediatric Clinics: Impact On Hpv, Mcv, And Tdap Initiation, Ross Shegog, Hanxiao Sun, Erica L Frost, Laura C Thormaehlen, Travis A Teague, Catherine Mary Healy, Hina Azam, Aadeel Khawaja, Laura Aubree Shay, Dale S Mantey, Sally W Vernon, Lara S Savas

Faculty, Staff and Students Publications

Introduction: HPV vaccination rates for adolescents in the United States are below recommended levels. The Adolescent Vaccination Program (AVP) guides pediatric clinics on how to implement evidence-based strategies to increase HPV vaccination rates. These strategies comprise the adoption of (1) immunization champions, (2) provider assessment and feedback, (3) continuing education, and (4) prompts, (5) parent reminders, and (6) parent education. The AVP systems-based intervention has demonstrated increased HPV vaccination rates in large urban pediatric clinic networks. The purpose of this study was to assess the feasibility of using an online decision support tool, the AVP Implementation Tool (AVP-IT), to …

Comparative Safety, Efficacy, And Predictors Of Complete Occlusion Of Flow Diverter Devices In The Treatment Of Unruptured Distal Anterior Cerebral Artery Aneurysms, Hamza Adel Salim, Luca Scarcia, Frédéric Clarençon, Orabi Hajjeh, Motaz Daraghma, Davide Simonato, Yan-Lin Li, Eimad Shotar, Kevin Premat, Ameer E. Hassan

School of Medicine Publications

Background: Flow diverters (FDs) are increasingly used for cerebral aneurysms, including distal anterior cerebral artery (DACA) aneurysms, but comparative data between devices in this challenging location are limited.

Objective: To compare the safety and efficacy of Pipeline, Silk Vista Baby (SVB), and FRED Jr. FDs for unruptured DACA aneurysms and identify predictors of complete occlusion.

Methods: We retrospectively analyzed 166 patients treated with FDs at 39 centers in 14 countries (2018–2022) from the CRETA registry. Outcomes included aneurysm occlusion (O’Kelly–Marotta [OKM] scale), complications, retreatment, modified Rankin Scale (mRS) scores, and independent predictors of complete occlusion using multivariable Cox regression.

Results: …

Neonatal Sepsis: Empiric Treatment And Monitoring Of Gentamicin Troughs In The Nicu, Aleese Palfreyman

Annual Research Symposium

No abstract provided.

Relationships Between Clinical Symptom Scales And Eeg Biomarkers In Oud Patients, Jess Delange, Benjamin M. Latey, John Glinski, Braden Ashcraft, Jasmine Pannu, Cassidy Beatty, Lauren Knudson, Benjamin Chafetz, Bryan Fugal, Patrick Tanner Brain, N P. Griffin, Christopher Gowans, Amanda Brandaris, Amanda Page, Blake D. Harris, Sophia Delgado, Lorissa Thorpe, Kyle Bills, Andrew Payne

Annual Research Symposium

This poster examines the relationship between clinical symptom scales and electroencephalographic (EEG) biomarkers in patients with Opioid Use Disorder (OUD). Participants from inpatient substance use treatment facilities completed validated mental health and withdrawal assessments, including the COWS, PHQ-9, HAM-A, and ASRS followed by cognitive testing while undergoing 19-lead EEG recording.

Preliminary findings indicate that synthetic opioid use is associated with prolonged P300 response latency across brain regions, suggesting measurable neurophysiologic differences tied to substance type and addiction severity. The study explores how EEG metrics may complement subjective symptom reporting to provide more objective markers of addiction status, co-morbid psychiatric burden, …

Mapping The Unexpected: Aberrant Celiac Trunk Origination With Atypical Splenic Artery Bifurcation, David A. Delano, Fernando D. Gonzalez, Franco R. Ramos, Parker J. Ballard

Annual Research Symposium

No abstract provided.

Imaging In Acute Neurovascular Emergencies: Optimizing Outcomes In Large Vessel Occlusion Stroke, Chandu Goli, Rohit Patel, Elliott Beard, Anna Liles, Saeed Saleh, Aleeza Namit, Alissa Ongaco, Kevin Steed Ph.D.

Annual Research Symposium

Purpose:

Large vessel occlusion (LVO) stroke is associated with high rates of morbidity and mortality, and patient outcomes are strongly influenced by rapid identification and timely reperfusion. Advances in acute neurovascular imaging have transformed stroke care by enabling precise patient selection, extending treatment windows, and accelerating clinical workflows. The purpose of this project is to evaluate how modern neurovascular imaging strategies influence treatment selection, workflow efficiency, and clinical outcomes in patients with acute LVO stroke.

Methods:

A narrative review of peer-reviewed literature published within the past decade was conducted. The review focused on CT-based imaging (non-contrast CT, CT angiography, CT …

Evaluating The American Society Of Hematology Quality Measure On Timeliness Of Analgesics For Sickle Cell Disease Pain Crisis, Ibrahim Gwarzo, Harish Chandra Dega, Paula Tanabe, Robin Miller, David C. Brousseau

Department of Medicine Faculty Papers

The American Society of Hematology (ASH) proposed the median time to first emergency department (ED) administration of pain medication for patients with sickle cell disease (SCD) vaso-occlusive pain episodes (VOE) as a site-level quality measure. Generalizable studies assessing current guideline adherence recommending pain medications within 60 minutes are lacking. We leveraged multisite electronic health record data from Epic's Cosmos research platform to analyze ED encounters for SCD VOE from 1 January 2019 to 31 December 2024, with administration of at least 1 pain medication. We calculated the quality measure (median time to first pain medication) and ranked sites based on …

Molecular Profiling And Tumor Biomarker Analysis Of Gog281/Logs: A Positive Late-Phase Trial Of Trametinib For Recurrent/Persistent Low-Grade Serous Ovarian Carcinoma, Robert L. Hollis, Austin Miller, Heather A. Lankes, Kwong-Kwok Wong, William Rodgers, David Millan, Karen Carty, Robert L. Coleman, Kathleen N. Moore, Angeles Alvarez Secord, David M. O'Malley, John K. Chan, Andrea R. Hagemann, Stephanie Gaillard, Saketh R. Guntupalli, Mitchell I. Edelson, Peter G. Rose, Oliver Dorigo, Susana Banerjee, Ailith Ewing, Michael Churchman, Anil K. Sood, C. Simon Herrington, Charlie Gourley, David M. Gershenson

Abington Jefferson Health Papers

PURPOSE: Low-grade serous ovarian carcinoma (LGSOC) is a distinct form of ovarian cancer characterized by younger patient age and relative chemoresistance. The GOG281/LOGS trial (NCT02101788) investigated the efficacy of the MEK inhibitor trametinib compared with physician's choice standard-of-care (SOC) in patients with LGSOC with persistent/recurrent disease. The study demonstrated significantly improved progression-free survival (PFS) in the trametinib-treated arm.

EXPERIMENTAL DESIGN: Two hundred and sixty patients with recurrent/persistent LGSOC were enrolled and randomly assigned in GOG281. We performed molecular analysis of 170 patients with available tumor specimens, comprising whole-exome sequencing and phospho-ERK (pERK) IHC, to identify biomarkers of clinical benefit from …

S6k1 Modulates Stat3 Activation To Promote Resistance To Radiotherapy In Lung Cancer, Ali Calderon-Aparicio, Noelle Francois, Tyler Grenda, Shan Xu, Olugbenga Okusanya, Jun He, Nicole L Simone

Department of Radiation Oncology Faculty Papers

Radiotherapy is a mainstay in the management of locally advanced lung cancer; however, intrinsic and acquired radioresistance contribute to poor prognosis. S6K1, a serine/threonine kinase, regulates cell growth, protein synthesis, and survival, and is increased in tumors, which is linked to enhanced survival under therapeutic stress, including radiation. The mechanisms, however, are not fully understood. This study investigates the role of S6K1 in lung cancer radioresistance and the mechanisms involved. Intrinsic radioresistance in lung cancer cells was associated with increased S6K1 activation. Pharmacologic inhibition or genetic deletion of S6K1 enhanced radiosensitivity both in vitro and in vivo, highlighting the therapeutic …

Tumor Microenvironment Transcriptional Activity Enables Robust Stratification Of Chemotherapy Response In Triple-Negative Breast Cancer, Yaoyi Dai, Xiaoxi Pan, Shuai Guo, Shuangxi Ji, Shaolong Cao, Matthew D Montierth, Yujie Jiang, Jeffrey T Chang, Leming Shi, Shabnam Shalapour, Gloria V Echeverria, Lucy Yates, Johan Staaf, Bora Lim, Yinyin Yuan, Wenyi Wang

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) exhibits heterogeneous treatment responses, yet molecular subtypes based on predefined biological pathways show limited prognostic value. We introduce tumor-specific total mRNA expression (TmS), a pathway-agnostic deconvolution metric derived from matched RNA/DNA sequencing, as a robust stratification tool. Analyzing 575 TNBC patients across Western and East Asian populations, TmS outperforms established subtypes in predicting chemotherapy outcomes, stratifying patients into high TmS with favorable prognosis and low TmS with poor prognosis. Stromal enrichment with immune exclusion emerges as a universal feature of chemotherapy-resistant low-TmS tumors across all cohorts. Population-specific features distinguish Asian cohorts: high-TmS tumors exhibit cell cycle-driven …

Syndecan-1-Targeted Therapeutic Antibody Impairs Macropinocytosis And Elicits Antitumor Immunity In Pancreatic Cancer, Zecheng Yang, Madelaine S Theardy, Shuaitong Chen, Yongkun Wei, Mitsunobu Takeda, Yue Zeng, Xiaofei Wang, Jun Yao, Jennifer Li, Prapassorn Thirasastr, Jangho Park, Yangxi Zheng, Long T Vien, Khalida M Wani, Huamin Wang, Sisi Gao, Tim Heffernan, Lawrence Kwong, Ignacio I Wistuba, Laura Bover, Giulio F Draetta, Haoqiang Ying, Wantong Yao

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with a 5-year survival rate of just 13%. While the development and early clinical use of small molecules targeting oncogenic KRAS mutations, key drivers of PDAC, have shown promise, resistance to these targeted therapies remains a significant challenge. We recently identified Syndecan-1 (SDC1), a highly expressed heparan sulfate proteoglycan, as a critical KRAS effector protein that promotes nutrient salvage and tumor growth. Here, we report the development of a human-specific monoclonal antibody (anti-SDC1 mAb) that inhibits PDAC cell proliferation in vitro and suppresses PDAC tumor growth in vivo. Mechanistically, …

Spatiotemporal Histogenesis Of The Developing Human Cerebellum Reveals Dynamic Layering Of Bergmann Glia, Guanyi He, Simon Du, Henry Tan, Sri Yellampally, Anders W Erickson, Virginia Fernandez, Ferechte Encha-Razavi, Kimberley A Phillips, Christine Haberler, Nicole Amberg, Victor Borrell, Paul A Northcott, Michael D Taylor, Kathleen J Millen, Parthiv Haldipur

Faculty, Staff and Students Publications

Bergmann glia (BG) are a specialized glial population essential for cerebellar development, yet their developmental timeline and molecular identity in the human cerebellum remain poorly understood. Here, we combined detailed histopathological analysis with spatial transcriptomics and single-nucleus RNA sequencing to generate a developmental atlas of human cerebellar BG. Histology revealed that BG emerge around 11 post-conception weeks (PCW), initially serving as a scaffold for Purkinje cells (PCs) migrating into the PC layer of the cerebellar cortex. Following the establishment of a multilayered PC arrangement, BG form a distinct parallel layer separated from the PCs by the lamina dissecans (LD), with …

The Impact Of Physical Activity And Diet On The Potassium-Chloride Cotransporter 2 In The Central Nervous System: A Literature Review, Benjamin M. Latey, Dustin Bowers, Andrew J. Payne

Annual Research Symposium

No abstract provided.