Life Sciences Commons^™

Mechanisms Of Resistance To Egfr-Targeted Therapies In Colorectal Cancer: More Than Just Genetics, Christine Parseghian, Madhulika Eluri, Scott Kopetz, Kanwal Raghav

Faculty, Staff and Student Publications

The development of acquired resistance to anti-EGFR therapies remains poorly understood, with most research to date exploring, and trying to overcome, various genomic mechanisms of resistance. However, recent work supports a model of resistance whereby transcriptomic mechanisms of resistance predominate in the presence of active cytotoxic chemotherapy combined with anti-EGFR therapy in the first-line setting, with a greater predominance of acquired MAPK mutations after single-agent anti-EGFR therapy in the later-line setting. The proposed model has implications for prospective studies evaluating anti-EGFR rechallenge strategies guided by acquired MAPK mutations and highlights the need to address transcriptional mechanisms of resistance.

Postoperative Management Of Recurrence After Radiosurgery And Surgical Resection For Brain Metastases And Predicting Benefit From Adjuvant Radiation, Samantha M Buszek, Benjamin Tran, James P Long, Dershan Luo, Dima Suki, Sherise Ferguson

Faculty, Staff and Student Publications

Stereotactic radiosurgery (SRS) is often used as upfront treatment for brain metastases. Progression or radionecrosis after SRS is common and can prompt resection. However, postoperative management strategies after resection for SRS failure vary widely, and no standard practice has been established. In this approved study, we retrospectively reviewed patients who received SRS for a brain metastasis followed by resection of the same lesion. We extracted patient-, disease-, and treatment-related variables and information on disease-related outcomes. Univariate and multivariate analyses of clinicopathologic variables were used to create a model to predict factors associated with local failure (LF). A total of 225 …

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

Faculty, Staff and Student Publications

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

Gankyrin-Mediated Interaction Between Cancer Cells And Tumor-Associated Macrophages Facilitates Prostate Cancer Progression And Androgen Deprivation Therapy Resistance, Guang Peng, Chao Wang, Hongru Wang, Min Qu, Keqin Dong, Yuquan Jiang, Xu Gao

Faculty, Staff and Student Publications

Increasing evidence reveals that the interaction between tumor cells and tumor-associated macrophages (TAMs) facilitates the progression of prostate cancer, but the related mechanisms remained unclear. This study determined how gankyrin, a component of the 19S regulatory complex of the 26S proteasome, regulates the progression and androgen deprivation therapy (ADT) resistance of prostate cancer through tumor cell-TAM interactions.

The Proteasome: A Key Modulator Of Nervous System Function, Brain Aging, And Neurodegenerative Disease, Kanisa Davidson, Andrew M Pickering

Faculty, Staff and Student Publications

The proteasome is a large multi-subunit protease responsible for the degradation and removal of oxidized, misfolded, and polyubiquitinated proteins. The proteasome plays critical roles in nervous system processes. This includes maintenance of cellular homeostasis in neurons. It also includes roles in long-term potentiation via modulation of CREB signaling. The proteasome also possesses roles in promoting dendritic spine growth driven by proteasome localization to the dendritic spines in an NMDA/CaMKIIα dependent manner. Proteasome inhibition experiments in varied organisms has been shown to impact memory, consolidation, recollection and extinction. The proteasome has been further shown to impact circadian rhythm through modulation of …

Population-Based Assessment Of The Burden Of Covid-19 Infection In African Countries: A First-Year Report Card And Public Health Implications, Osaro Mgbere, Ogbonna Collins Nwabuko, Olajumoke A Olateju, Omolola E Adepoju, Winston Liaw, Ekere James Essien

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic constitutes a global health threat and poses a major burden on the African continent. We assessed the real-world burden of COVID-19 infection in African Union (AU) member states to determine the distributional patterns of epidemiological measures during the first 1 year of the pandemic.

METHODS: This retrospective cross-sectional study utilized COVID-19 data from publicly available data repositories of the African Center for Disease Control and Prevention and

RESULTS: A total of 3.21 million cases were reported during the 1-year period, with 2.6 million recoveries, 536,784 cases remaining active, and 77,486 deaths. Most countries (49.1%,

CONCLUSION: Understanding …

Predictive Capacity Of A Mirna Panel In Identifying Teratoma In Post-Chemotherapy Consolidation Surgeries, Joseph A Moore, Michael J Lehner, Simone Anfossi, Saumil Datar, Rebecca S Tidwell, Amishi Y Shah, Jose A Karam, Christopher G Wood, Lois L Pisters, George A Calin, Shi-Ming Tu

Faculty, Staff and Student Publications

OBJECTIVES: To investigate the utility of a novel serum miRNA biomarker panel to distinguish teratoma from nonmalignant necrotic/fibrotic tissues or nonviable tumours in patients with NSGCT undergoing post-chemotherapy consolidation surgery.

PATIENTS AND METHODS: We prospectively collected pre-surgical serum samples from 22 consecutive testicular NSGCT patients with residual NSGCT after chemotherapy undergoing post-chemotherapy consolidation surgery. We measured serum miRNA expression of four microRNAs (miRNA-375, miRNA-200a-3p, miRNA-200a-5p and miRNA-200b-3p) and compared with pathologic findings at time of surgery. Receiver operating characteristic (ROC) curves were performed to assess the ability of these miRNA to differentiate between teratoma and necrosis or viable malignancy.

RESULTS: …

Ribonuclease 1 Enhances Antitumor Immunity Against Breast Cancer By Boosting T Cell Activation, Ying-Nai Wang, Heng-Huan Lee, Zhou Jiang, Li-Chuan Chan, Gabriel N Hortobagyi, Mien-Chie Hung

Faculty, Staff and Student Publications

The secretory enzyme human ribonuclease 1 (RNase1) is involved in innate immunity and anti-inflammation, achieving host defense and anti-cancer effects; however, whether RNase1 contributes to adaptive immune response in the tumor microenvironment (TME) remains unclear. Here, we established a syngeneic immunocompetent mouse model in breast cancer and demonstrated that ectopic RNase1 expression significantly inhibited tumor progression. Overall changes in immunological profiles in the mouse tumors were analyzed by mass cytometry and showed that the RNase1-expressing tumor cells significantly induced CD4+ Th1 and Th17 cells and natural killer cells and reduced granulocytic myeloid-derived suppressor cells, supporting that RNase1 favors an antitumor …

Radiotherapy Reimagined: Integrating Nanomedicines Into Radiotherapy Clinical Trials, Allison N Duross, Jack Phan, Alexander J Lazar, Joshua M Walker, Alexander R Guimaraes, Sunil Krishnan, Conroy Sun, Alexander F Bagley

Faculty, Staff and Student Publications

Radioenhancing nanoparticles (NPs) are being evaluated in ongoing clinical trials for various cancers including head and neck, lung, esophagus, pancreas, prostate, and soft tissue sarcoma. Supported by decades of preclinical investigation and recent randomized trial data establishing clinical activity, these agents are poised to influence future multimodality treatment paradigms involving radiotherapy. Although the physical interactions between NPs and ionizing radiation are well characterized, less is known about how these agents modify the tumor microenvironment, particularly regarding tumor immunogenicity. In this review, we describe the key multidisciplinary considerations related to radiation, surgery, immunology, and pathology for designing radioenhancing NP clinical trials. …

Experiential Exposure As The Key To Recruiting Medical Students Into Pathology, Ashley M Holloman, Mary P Berg, Bronwyn Bryant, Lisa Ross Dixon, Melissa R George, Barbara Ec Knollmann-Ritschel, Charles F Timmons, John Michael Childs, Amanda Lofgreen, Kristen Johnson, Cindy B Mccloskey

Faculty, Staff and Student Publications

Medical student interest and pursuit of a career in pathology have been steadily declining since 2015. We conducted three separate surveys of medical students to better understand these trends. In our first survey, we focused on assessing U.S. allopathic medical students understanding and perceptions of pathology. We later surveyed U.S. osteopathic medical students as a companion to the allopathic medical student survey, in which many similarities were discovered with some key differences. In our final survey, we specifically looked at curriculum differences between the U.S. allopathic medical schools that graduate the most students who enter pathology training programs (Group 1) …

Applying Ht-Saxs To Chemical Ligand Screening, Chris A Brosey, Runze Shen, Davide Moiani, Darin E Jones, Kathryn Burnett, John A Tainer

Faculty, Staff and Student Publications

Chemical probes are invaluable tools for investigating essential biological processes. Understanding how small-molecule probes engage biomolecular conformations is critical to developing their functional selectivity. High-throughput solution X-ray scattering is well-positioned to profile target-ligand complexes during probe development, bringing conformational insight and selection to traditional ligand binding assays. Access to high-quality synchrotron SAXS datasets and high-throughput data analysis now allows routine academic users to incorporate conformational information into small-molecule development pipelines. Here we describe a general approach for benchmarking and preparing HT-SAXS chemical screens from small fragment libraries. Using the allosteric oxidoreductase Apoptosis-Inducing Factor (AIF) as an exemplary system, we illustrate …

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

Faculty, Staff and Student Publications

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

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

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

Faculty, Staff and Student Publications

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

Computed Tomography: State-Of-The-Art Advancements In Musculoskeletal Imaging, Hamza Ahmed Ibad, Cesar De Cesar Netto, Delaram Shakoor, Alejandro Sisniega, Stephen Z Liu, John A Carrino, Shadpour Demehri

Faculty, Staff and Student Publications

Although musculoskeletal magnetic resonance imaging (MRI) plays a dominant role in characterizing abnormalities, novel computed tomography (CT) techniques have found an emerging niche in several scenarios such as trauma, gout, and the characterization of pathologic biomechanical states during motion and weight-bearing. Recent developments and advancements in the field of musculoskeletal CT include 4-dimensional, cone-beam (CB), and dual-energy (DE) CT. Four-dimensional CT has the potential to quantify biomechanical derangements of peripheral joints in different joint positions to diagnose and characterize patellofemoral instability, scapholunate ligamentous injuries, and syndesmotic injuries. Cone-beam CT provides an opportunity to image peripheral joints during weight-bearing, augmenting the …

Association Of Immune-Related Adverse Events With The Outcomes Of Immune Checkpoint Inhibitors In Patients With Dmmr/Msi-H Metastatic Colorectal Cancer, Vincenzo Nasca, Francesco Barretta, Francesca Corti, Sara Lonardi, Monica Niger, Marwan Fakih, Aakash Tushar Shah, Massimiliano Salati, Elisabetta Fenocchio, Lisa Salvatore, Chiara Cremolini, Javier Ros, Margherita Ambrosini, Giacomo Mazzoli, Rossana Intini, Michael J Overman, Rosalba Miceli, Filippo Pietrantonio

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs) show a tremendous activity in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), but a consistent fraction of patients does not respond. Prognostic/predictive markers are needed. Despite previous investigations in other tumor types, immune-related adverse events (irAEs) have not been well evaluated in patients with MSI-H cancers treated with ICIs.

METHODS: We conducted an international cohort study at tertiary cancer centers collecting clinic-pathological features from 331 patients with MSI-H mCRC treated with ICIs. Of note, the irAEs were summarized using a 'burden score' constructed in a way that the same score value could be obtained by …

The Short- And Long-Term Readmission Of Four Major Categories Of Digestive System Cancers: Does Obesity Or Metabolic Disorder Matter?, Yan Li, Xiaoqin Wu, Yongfeng Song, Peipei Wang, Bofei Zhang, Ziwei Liu, Shanshan Shao, Yiping Cheng, Honglin Guo, Xiude Fan, Jiajun Zhao

Faculty, Staff and Student Publications

Purpose: Patients with digestive system cancers (DSCs) are at a high risk for hospitalizations; however, the risk factors for readmission remain unknown. Here, we established a retrospective cohort study to assess the association between metabolic obesity phenotypes and readmission risks of DSC.

Experimental design: A total of 142,753 and 74,566 patients at index hospitalization were ultimately selected from the Nationwide Readmissions Database (NRD) 2018 to establish the 30-day and 180-day readmission cohorts, respectively. The study population was classified into four groups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). Multivariate Cox …

The Mediating Effect Of Resilience On The Relationship Between Symptom Burden And Anxiety/Depression Among Chinese Patients With Primary Liver Cancer After Liver Resection, Xue Zhang, Haoran Zhang, Zonghao Zhang, Hua Fan, Shuwen Li

Faculty, Staff and Student Publications

Purpose: Primary liver cancer (PLC) is a common cancer of the digestive system. Patients with PLC often experience a heavy symptom burden and along with a significant levels of anxiety and depression after liver resection. High levels of symptom burden can lead to increased anxiety and depression, whereas high levels of resilience can alleviate these conditions. Therefore, we aimed to explore the relationships among symptom burden, resilience, and anxiety/depression in Chinese patients with PLC after liver resection and to determine whether resilience mediates the relationship between symptom burden and anxiety/depression.

Patients and methods: A total of 223 postoperative PLC patients …

Effects Of Heterozygous Deletion Of Autism-Related Gene Cullin-3 In Mice, Qiang-Qiang Xia, Angela K Walker, Chenghui Song, Jing Wang, Anju Singh, Zhong X Xuan, Craig M Powell

Faculty, Staff and Student Publications

Autism Spectrum Disorder (ASD) is a developmental disorder in which children display repetitive behavior, restricted range of interests, and atypical social interaction and communication. CUL3, coding for a Cullin family scaffold protein mediating assembly of ubiquitin ligase complexes through BTB domain substrate-recruiting adaptors, has been identified as a high-risk gene for autism. Although complete knockout of Cul3 results in embryonic lethality, Cul3 heterozygous mice have reduced CUL3 protein, demonstrate comparable body weight, and display minimal behavioral differences including decreased spatial object recognition memory. In measures of reciprocal social interaction, Cul3 heterozygous mice behaved similarly to their wild-type littermates. In area …

Accommodating Time-Varying Heterogeneity In Risk Estimation Under The Cox Model: A Transfer Learning Approach, Ziyi Li, Yu Shen, Jing Ning

Faculty, Staff and Student Publications

Transfer learning has attracted increasing attention in recent years for adaptively borrowing information across different data cohorts in various settings. Cancer registries have been widely used in clinical research because of their easy accessibility and large sample size. Our method is motivated by the question of how to utilize cancer registry data as a complement to improve the estimation precision of individual risks of death for inflammatory breast cancer (IBC) patients at The University of Texas MD Anderson Cancer Center. When transferring information for risk estimation based on the cancer registries (i.e., source cohort) to a single cancer center (i.e., …

Financial Toxicity In Cancer Patients And Subsequent Risk Of Repeat Acute Care Utilization, Julia J Shi, J Alberto Maldonado, Chi-Fang Wu, Susan K Peterson, Ying-Shiuan Chen, Robert J Volk, Ya-Chen T Shih, Kelsey Kaiser, Grace L Smith

Faculty, Staff and Student Publications

Background: Acute care (AC) visits by cancer patients are costly sources of healthcare resources and can exert a financial burden of oncology care both for individuals with cancer and healthcare systems. We sought to identify whether cancer patients who reported more severe initial financial toxicity (FT) burdens shouldered excess risks for acute care utilization.

Methods: In 225 adult patients who participated in the Economic Strain and Resilience in Cancer (ENRICh) survey study of individuals receiving ambulatory cancer care between March and September 2019, we measured the baseline FT (a multidimensional score of 0-10 indicating the least to most severe global, …

Editorial: Advances In Mathematical And Computational Oncology, Volume Iii, George Bebis, Mamoru Kato, Mohammad Kohandel, Kathleen Wilkie, Dinler A Antunes, Jinzhuang Dou

Faculty, Staff and Student Publications

No abstract provided.

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

Faculty, Staff and Student Publications

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

Comparing Cigarette-Cue Attentional Bias Between People With Hiv/Aids And People With Opioid Use Disorder Who Smoke, Gopalkumar Rakesh, Joseph L Alcorn, Rebika Khanal, Seth S Himelhoch, Craig R Rush

Faculty, Staff and Student Publications

BACKGROUND: Special populations like people living with HIV/AIDS (PLWHA) and people with opioid use disorder (OUD) smoke tobacco cigarettes at rates three to four times greater than the general population. Patients with tobacco use disorder exhibit attentional bias (AB) for cigarette cues. Eye tracking can quantify this bias by measuring fixation time (FT) on cigarette and matched neutral cues, to calculate an AB score. Although previous studies have measured this bias in people who smoke without any other comorbid conditions, no study, to our knowledge, has measured or compared this bias in special populations.

METHODS: We performed exploratory analyses on …

A Randomized Double-Blind Prospective Study Comparing The Efficacy Of Subperiosteal And Periarticular Injections Of A Local Anesthetic For Postoperative Pain Management After Total Knee Arthroplasty, Reza Minaei, Mohammad Salehpour, Emad Kouhestani, Mahshid Ghasemi

Faculty, Staff and Student Publications

OBJECTIVES: Total knee arthroplasty (TKA) serves as an effective surgical treatment method for advanced osteoarthritis (OA). Nonetheless, it is associated with postoperative pain that can influence patients' functional outcome. This study aimed to compare the analgesic effect of subperiosteal and periarticular injection methods of a special local anesthetic in patients who underwent TKA.

METHODS: This double-blind prospective clinical study was conducted on patients with advanced knee OA who underwent TKA. Patients were randomly divided into two groups, with a local anesthetic (21 ml) administered either in periarticular (P group) or subperiosteal (S group) forms prior to wound closure. The local …

Plasma Enzymatic Activity, Proteomics And Peptidomics In Covid-19-Induced Sepsis: A Novel Approach For The Analysis Of Hemostasis, Fernando Dos Santos, Joyce B Li, Nathalia Juocys, Rafi Mazor, Laura Beretta, Michael T Y Lam, Maria Claudia Irigoyen, Anthony J O'Donoghue, Federico Aletti, Erik B Kistler

Faculty, Staff and Student Publications

Introduction: Infection by SARS-CoV-2 and subsequent COVID-19 can cause viral sepsis. We investigated plasma protease activity patterns in COVID-19-induced sepsis with bacterial superinfection, as well as plasma proteomics and peptidomics in order to assess the possible implications of enhanced proteolysis on major protein systems (e.g., coagulation). Methods: Patients (=4) admitted to the intensive care units (ICUs) at the University of California, San Diego (UCSD) Medical Center with confirmed positive test for COVID-19 by real-time reverse transcription polymerase chain reaction (RT-PCR) were enrolled in a study approved by the UCSD Institutional Review Board (IRB# 190699, Protocol #20-0006). Informed consent was obtained …

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

Faculty, Staff and Student Publications

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

Benchmarking Outcomes For Molecularly Characterized Synchronous Oligometastatic Non-Small-Cell Lung Cancer Reveal, Brian De, Ahsan S Farooqi, Kyle G Mitchell, Ethan B Ludmir, Jeff Lewis, Vadeerat Rinsurongkawong, Stephen G Swisher, Don L Gibbons, Jianjun Zhang, Xiuning Le, Yasir Y Elamin, Daniel R Gomez, Matthew S Ning, Steven H Lin, Zhongxing Liao, Joe Y Chang, Ara A Vaporciyan, John V Heymach, Mara B Antonoff, Saumil J Gandhi

Faculty, Staff and Student Publications

Purpose: Local consolidative therapy (LCT) for patients with synchronous oligometastatic non-small-cell lung cancer is an evolving treatment strategy, but outcomes following LCT stratified by genetic mutations have not been reported. We sought to identify genomic associations with overall survival (OS) and progression-free survival (PFS) for these patients.

Methods: We identified all patients presenting between 2000 and 2017 with stage IV non-small-cell lung cancer and ≤ 3 synchronous metastatic sites. Patients were grouped according to mutational statuses. Primary outcomes included OS and PFS following initial diagnosis.

Results: Of 194 included patients, 121 received comprehensive LCT to all sites of disease with …

Effectiveness Without Efficacy: Cautionary Tale From A Landmark Breast Cancer Randomized Controlled Trial, Yu Shen, Jing Ning, Heather Y Lin, Simona F Shaitelman, Henry M Kuerer

Faculty, Staff and Student Publications

Background: “Old” randomized controlled trials established breast conserving therapy (BCT) and total mastectomy (TM) equivalence for treating early breast cancer, whereas recent literature report improved survival with BCT. To reconcile this, we performed a simulation study and re-analyzed B-06 trial data.

Methods: We estimated the distributions for overall survival (OS), cumulative incidence functions for breast-cancer-specific death (BCSD) and other causes-specific death (OCSD) by BCT and TM. The restricted mean survival time (RMST) difference and hazard ratio between the two arms were estimated. Given the estimated distributions, we simulated cause-specific death times from each arm, evaluating the power to test treatment …

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

Faculty, Staff and Student Publications

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

Cd73-Generated Extracellular Adenosine Promotes Resolution Of Neutrophil-Mediated Tissue Injury And Restrains Metaplasia In Pancreatitis, Baylee J O'Brien, Erika Y Faraoni, Lincoln N Strickland, Zhibo Ma, Victoria Mota, Xuebo Chen, Holger K Eltzschig, Kathleen E Delgiorno, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatitis is currently the leading cause of gastrointestinal hospitalizations in the US. This condition occurs in response to abdominal injury, gallstones, chronic alcohol consumption or, less frequently, the cause remains idiopathic. CD73 is a cell surface ecto‐5′‐nucleotidase that generates extracellular adenosine, which can contribute to resolution of inflammation by binding adenosine receptors on infiltrating immune cells. We hypothesized genetic deletion of CD73 would result in more severe pancreatitis due to decreased generation of extracellular adenosine. CD73 knockout (CD73 −/−) and C57BL/6 (wild type, WT) mice were used to evaluate the progression and response of caerulein‐induced acute and chronic pancreatitis. …