Medical Specialties Commons^™

Transcriptome-Wide Profiling Of Acute Stress Induced Changes In Ribosome Occupancy Level Using External Standards, Annie W Shieh, Sandeep K Bansal, Zhen Zuo, Sidney H Wang

Faculty, Staff and Student Publications

Acute cellular stress is known to induce a global reduction in mRNA translation through suppression of cap dependent translation. Selective translation in response to acute stress has been shown to play important roles in regulating the stress response. However, accurately profiling translational changes transcriptome-wide in response to acute cellular stress has been challenging. Commonly used data normalization methods operate on the assumption that any systematic shifts are experimental artifacts. Consequently, if applied to profiling acute cellular stress-induced mRNA translation changes, these methods are expected to produce biased estimates. To address this issue, we designed, produced, and evaluated a panel of …

Fgf Signaling In Cranial Suture Development And Related Diseases, Xiaolei Zhao, Shannon Erhardt, Kihan Sung, Jun Wang

Faculty, Staff and Student Publications

Suture mesenchymal stem cells (SMSCs) are a heterogeneous stem cell population with the ability to self-renew and differentiate into multiple cell lineages. The cranial suture provides a niche for SMSCs to maintain suture patency, allowing for cranial bone repair and regeneration. In addition, the cranial suture functions as an intramembranous bone growth site during craniofacial bone development. Defects in suture development have been implicated in various congenital diseases, such as sutural agenesis and craniosynostosis. However, it remains largely unknown how intricate signaling pathways orchestrate suture and SMSC function in craniofacial bone development, homeostasis, repair and diseases. Studies in patients with …

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, Maria Elena Elez, Marwan Fakih, Priya Jayachandran, 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 …

Wnt Signaling In Liver Regeneration, Disease, And Cancer, Gengyi Zou, Jae-Il Park

Faculty, Staff and Student Publications

The liver exhibits the highest recovery rate from acute injuries. However, in chronic liver disease, the long-term loss of hepatocytes often leads to adverse consequences such as fibrosis, cirrhosis, and liver cancer. The Wnt signaling plays a pivotal role in both liver regeneration and tumorigenesis. Therefore, manipulating the Wnt signaling has become an attractive approach to treating liver disease, including cancer. Nonetheless, given the crucial roles of Wnt signaling in physiological processes, blocking Wnt signaling can also cause several adverse effects. Recent studies have identified cancer-specific regulators of Wnt signaling, which would overcome the limitation of Wnt signaling target approaches. …

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, Yongwei Yu, Yuquan Jiang, Sishun Gan, 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.

Bayesian Feature Selection For Radiomics Using Reliability Metrics, Katherine Shoemaker, Rachel Ger, Laurence E Court, Hugo Aerts, Marina Vannucci, Christine B Peterson

Faculty, Staff and Student Publications

Introduction: Imaging of tumors is a standard step in diagnosing cancer and making subsequent treatment decisions. The field of radiomics aims to develop imaging based biomarkers using methods rooted in artificial intelligence applied to medical imaging. However, a challenging aspect of developing predictive models for clinical use is that many quantitative features derived from image data exhibit instability or lack of reproducibility across different imaging systems or image-processing pipelines. Methods: To address this challenge, we propose a Bayesian sparse modeling approach for image classification based on radiomic features, where the inclusion of more reliable features is favored via a probit …

Characteristics Of Pediatric Covid-19 Infections And The Impact Of Influenza And Covid-19 Vaccinations During The First Two Years Of The Pandemic, Mahmoud Ali, Lynette Phillips, David C Kaelber, Hulya Bukulmez

Faculty, Staff and Student Publications

The data regarding the demographics of SARS-CoV-2 in the pediatric population has been published based on several single-center experiences or on metanalyses over short time frames. This article reports data on the demographics of pediatric patients with COVID-19 on a global scale using the TriNetX COVID-19 Research Network. In addition, we examined the risk of COVID-19 infection in relation to the body mass index (BMI) category and the protective value of influenza and COVID-19 immunization against COVID-19 infection. The incidence of COVID-19 infection was higher in the younger age group (≤6 years old), but no gender differences. The incidence of …

Protein Translation Paradox: Implications In Translational Regulation Of Aging, Harper S Kim, Andrew M Pickering

Faculty, Staff and Student Publications

Protein translation is an essential cellular process playing key roles in growth and development. Protein translation declines over the course of age in multiple animal species, including nematodes, fruit flies, mice, rats, and even humans. In all these species, protein translation transiently peaks in early adulthood with a subsequent drop over the course of age. Conversely, lifelong reductions in protein translation have been found to extend lifespan and healthspan in multiple animal models. These findings raise the protein synthesis paradox: age-related declines in protein synthesis should be detrimental, but life-long reductions in protein translation paradoxically slow down aging and prolong …

Evaluation Of Scrub Typhus Surveillance, Alwar District, Rajasthan, India, July-August 2020, Surendra M Prajapati, Kanica Kaushal, Simmi Tiwari, Ajit Shewale, Tushar Nale, Tanzin Dikid

Faculty, Staff and Student Publications

INTRODUCTION: Scrub typhus is one of the most underreported and fatal illnesses accounting for 23% of all febrile illness. Rajasthan reported cases during 2018-2019 in state reporting system but did not report any case to central Integrated Disease Surveillance Programme (IDSP) unit. We evaluated the Scrub typhus surveillance system in Alwar district, Rajasthan, with the objective of describing and evaluating the system and providing evidence-based recommendations to identify gaps.

MATERIAL AND METHODS: In cross-sectional study, we reviewed records and conducted key informant interviews at district- and block-level health facilities. Using US Centers for Disease Control guidelines, we evaluated the system …

How Influential Are Medical School Curriculum And Other Medical School Characteristics In Students' Selecting Pathology As A Specialty?, Cindy B Mccloskey, Mark Brissette, John Michael Childs, Amanda Lofgreen, Kristen Johnson, Melissa R George, Ashley M Holloman, Bronwyn Bryant, Mary P Berg, Lisa Ross Dixon, Julie Katz Karp, Barbara E C Knollmann-Ritschel, Victor Gerardo Prieto, Charles F Timmons, Robert D Hoffman

Faculty, Staff and Student Publications

There has been a significant decline in the number of United States allopathic medical students matching to pathology residency programs. Data acquired from the American Association of Medical Colleges (AAMC) show sustained variation in the medical school production of students who go on to pathology residency. When divided into groups based on the medical school's historical volume of graduates entering pathology, the schools in groups labeled Group 1 and Group 2 produced significantly higher and lower proportions of pathology residents, respectively. This study aimed to identify what medical school curriculum elements and other medical school characteristics might explain the differences …

Tuning The Thermodynamic, Optical, And Rheological Properties Of Thermoresponsive Polymer Solutions Via Silica Nanoparticle Shape And Concentration, Christopher A P Neal, Valeria León, Michelle C Quan, Nondumiso O Chibambo, Michelle A Calabrese

Faculty, Staff and Student Publications

HYPOTHESIS: The shape and quantity of hydrophilic silica nanoparticles (NPs) can be used to tune the microstructure, rheology, and stability of phase-separating polymer solutions. In thermoresponsive polymer systems, silica nanospheres are well-studied whereas anisotropic NPs have little literature precedent. Here, we hypothesize that NP shape and concentration lower the onset of rheological and turbidimetric transitions of aqueous poly(N-isopropyl acrylamide) (PNIPAM) solutions.

EXPERIMENTS: Differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), turbidimetry, and oscillatory rheology are utilized to examine interactions between NPs, PNIPAM, and water and to track changes in phase separation and rheological properties due to NP concentration and shape. …

Next-Generation Ctla-4 Targeting Molecules And Combination Therapy: Promising Strategies For Improving Cancer Immunotherapy, Nils-Petter Rudqvist, Manushak Avagyan, Dhan Chand

Faculty, Staff and Student Publications

Radiation therapy and anti-CTLA-4 combination therapy can induce meaningful responses in some patients. Adding CD40 may provide additional benefit. Next-generation anti-CTLA-4 antibodies, such as botensilimab, are showing promise in clinical trials. Combining botensilimab with RT and/or CD40 agonist may offer additional benefits for challenging tumor types.

Stereotactic Body Proton Therapy For Early Stage Non-Small Cell Lung Cancer – Technical Challenges And Solutions: The Md Anderson Experience, X Ronald Zhu, Yuting Li, Ming Yang, Thomas J Whitaker, Paige A Taylor, Xiaodong Zhang, Falk Poenisch, Narayan Sahoo, Zhongxing Liao, Joe Y Chang

Faculty, Staff and Student Publications

Our randomized clinical study comparing stereotactic body radiotherapy (SBRT) and stereotactic body proton therapy (SBPT) for early stage non-small cell lung cancer (NSCLC) was closed prematurely owing to poor enrollment, largely because of lack of volumetric imaging and difficulty in obtaining insurance coverage for the SBPT group. In this article, we describe technology improvements in our new proton therapy center, particularly in image guidance with cone beam CT (CBCT) and CT on rail (CTOR), as well as motion management with real-time gated proton therapy (RGPT) and optical surface imaging. In addition, we have a treatment planning system that provides better …

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 …

Multi-Faceted Role Of Lrp1 In The Immune System, Olga Sizova, Lisa St John, Qing Ma, Jeffrey J Molldrem

Faculty, Staff and Student Publications

Graft versus host disease (GVHD) represents the major complication after allogeneic hematopoietic stem cell transplantation (Allo-SCT). GVHD-prone patients rely on GVHD prophylaxis (e.g. methotrexate) and generalized anti-GVHD medical regimen (glucocorticoids). New anti-GVHD therapy strategies are being constantly explored, however there is an urgent need to improve current treatment, since GVHD-related mortality reaches 22% within 5 years in patients with chronic GVHD. This review is an attempt to describe a very well-known receptor in lipoprotein studies - the low-density lipoprotein receptor related protein 1 (LRP1) - in a new light, as a potential therapeutic target for GVHD prevention and treatment. Our …

Colorectal Surveillance Outcomes From An Institutional Longitudinal Cohort Of Lynch Syndrome Carriers, Gabriel Del Carmen, Laura Reyes-Uribe, Daniel Goyco, Kyera Evans, Charles M Bowen, Jennifer L Kinnison, Valerie O Sepeda, Diane M Weber, Julie Moskowitz, Maureen E Mork, Selvi Thirumurthi, Patrick M Lynch, Miguel A Rodriguez-Bigas, Melissa W Taggart, Y Nancy You, Eduardo Vilar

Faculty, Staff and Student Publications

OBJECTIVE: Lynch Syndrome (LS) carriers have a significantly increased risk of developing colorectal cancer (CRC) during their lifetimes. Further stratification of this patient population may help in identifying additional risk factors that predispose to colorectal carcinogenesis. In most LS patients CRC may arise from adenomas, although an alternative non-polypoid carcinogenesis pathway has been proposed for

DESIGN: We collected demographics, genetic, colonoscopy, and pathology results from a total of 163 LS carriers who obtained regular screening care at MD Anderson Cancer Center. Data were extracted from the electronic health records into a REDCap database for analysis. Logistic regressions were performed to …

Exercise And Ischemia-Activated Pathways In Limb Muscle Angiogenesis And Vascular Regeneration, Vihang A Narkar

Faculty, Staff and Student Publications

Exercise has a profound effect on cardiovascular disease, particularly through vascular remodeling and regeneration. Peripheral artery disease (PAD) is one such cardiovascular condition that benefits from regular exercise or rehabilitative physical therapy in terms of slowing the progression of disease and delaying amputations. Various rodent pre-clinical studies using models of PAD and exercise have shed light on molecular pathways of vascular regeneration. Here, I review key exercise-activated signaling pathways (nuclear receptors, kinases, and hypoxia inducible factors) in the skeletal muscle that drive paracrine regenerative angiogenesis. The rationale for highlighting the skeletal muscle is that it is the largest organ recruited …

Fanconi Anemia Caused By Biallelic Inactivation Of Brca2 Can Present With An Atypical Cancer Phenotype In Adulthood, Kara N Maxwell, Vishal Patel, Kevin T Nead, Shana Merrill, Dana Clark, Qinqin Jiang, Bradley Wubbenhorst, Kurt D'Andrea, Roger B Cohen, Susan M Domchek, Jennifer J D Morrissette, Roger A Greenberg, Daria V Babushok, Katherine L Nathanson

Faculty, Staff and Student Publications

Inherited biallelic pathogenic variants (PVs) in BRCA2 cause Fanconi Anemia complementation group D1 (FA-D1), a severe pediatric bone marrow failure and high-risk cancer syndrome. We identified biallelic BRCA2 PVs in a young adult with multiple basal cell carcinomas, adult-onset colorectal cancer and small cell neuroendocrine carcinoma, without bone marrow failure. No PVs were identified in any other known cancer susceptibility gene, and there was no evidence of reversion mosaicism. The proband's deceased sister had a classic FA-D1 presentation and was shown to carry the same biallelic BRCA2 PVs. A lymphoblastoid cell line derived from the proband demonstrated hypersensitivity to DNA …

A Student-Designed Multimodal Sex- And Gender-Based Women's Health Elective Program: Advocacy Curriculum For Medical Students, Lauren M Conroy, Danna Ghafir, Maitreyi Narayan, Hunter Mcspedden, Samuel Neher, S Shahrukh Hashmi, Rebecca Lunstroth

Faculty, Staff and Student Publications

OBJECTIVES: The objective of this article is to describe the design and implementation of a multimodal, student-driven, sex- and gender-based women's health (SGBWH) elective with a curricular focus on patient and legislative advocacy. In this single arm, pre/post design, interventional study, we detail and evaluate the use of social media, newsletters, and round-table discussions in conjunction with a traditional lecture-based educational format to engage medical students in a virtual learning environment.

METHODS: We developed a 22-week SGBWH curriculum for pre-clinical and clinical medical students, which included a series of lectures on multi-specialty and gender-inclusive topics related to SGBWH, small group …

Methodological Considerations In Pisces 3: A Randomized, Placebo-Controlled Study Of Intracerebral Stem Cells In Subjects With Disability Following An Ischemic Stroke, Daniel T Laskowitz, Keith W Muir, Sean I Savitz, Lawrence R Wechsler, Julie G Pilitsis, Scott Y Rahimi, Richard L Beckman, Vincent Holmes, Peng R Chen, Laura Juel, Deborah Koltai, Brad J Kolls

Faculty, Staff and Student Publications

Background and hypothesis: At present, there are no medical interventions proven to improve functional recovery in patients with subacute stroke. We hypothesize that the intraparenchymal administration of CTX0E03, a conditionally immortalized neural stem cell line, linked with a standardized rehabilitation therapy regimen for the upper limb, would improve functional outcomes in patients 6-12 months after an index ischemic stroke.

Study design: PISCES III was designed as a multicenter prospective, sham-controlled, outcome-blinded randomized clinical trial. Eligibility required a qualifying ischemic stroke 6-12 months prior to surgical intervention. Patients must be between 35 and 75 years of age and have residual moderate …

Novornabreak: Local Assembly For Novel Splice Junction And Fusion Transcript Detection From Rna-Seq Data, Yukun Tan, Vakul Mohanty, Shaoheng Liang, Jinzhuang Dou, Jun Ma, Kun Hee Kim, Marc Jan Bonder, Xinghua Shi, Charles Lee, Zechen Chong, Ken Chen

Faculty, Staff and Student Publications

We present novoRNABreak, a unified framework for cancer specific novel splice junction and fusion transcript detection in RNA-seq data obtained from human cancer samples. novoRNABreak is based on a local assembly model, which offers a tradeoff between the alignment-based and de novo whole transcriptome assembly (WTA) methods. This approach is accurate and sensitive in assembling novel junctions that are difficult to directly align or have multiple alignments. Additionally, it is more efficient due to the strategy that focuses on junctions rather than full length transcripts. The performance of novoRNABreak is demonstrated by a comprehensive set of experiments using synthetic data …

Automated Brain Metastases Segmentation With A Deep Dive Into False-Positive Detection, Hamidreza Ziyaee, Carlos E Cardenas, D Nana Yeboa, Jing Li, Sherise D Ferguson, Jason Johnson, Zijian Zhou, Jeremiah Sanders, Raymond Mumme, Laurence Court, Tina Briere, Jinzhong Yang

Faculty, Staff and Student Publications

Purpose: The clinical management of brain metastases after stereotactic radiosurgery (SRS) is difficult, because a physician must review follow-up magnetic resonance imaging (MRI) scans to determine treatment outcome, which is often labor intensive. The purpose of this study was to develop an automated framework to contour brain metastases in MRI to help treatment planning for SRS and understand its limitations.

Methods and materials: Two self-adaptive nnU-Net models trained on postcontrast 3-dimensional T1-weighted MRI scans from patients who underwent SRS were analyzed. Performance was evaluated by computing positive predictive value (PPV), sensitivity, and Dice similarity coefficient (DSC). The training and testing …

Pathologic And Molecular Insights In Nodal T-Follicular Helper Cell Lymphomas, Mario L Marques-Piubelli, Catalina Amador, Francisco Vega

Faculty, Staff and Student Publications

T-follicular helper (TFH) cells are one of the T-cell subsets with a critical role in the regulation of germinal center (GC) reactions. TFH cells contribute to the positive selection of GC B-cells and promote plasma cell differentiation and antibody production. TFH cells express a unique phenotype characterized by PD-1hi, ICOShi, CD40Lhi, CD95hi, CTLAhi, CCR7lo, and CXCR5hi . Three main subtypes of nodal TFH lymphomas have been described: 1) angioimmunoblastic-type, 2) follicular-type, and 3) not otherwise specified (NOS). The diagnosis of these neoplasms can be challenging, and it is rendered based on a combination of clinical, laboratory, histopathologic, immunophenotypic, and molecular …

When Guilt Works: A Comprehensive Meta-Analysis Of Guilt Appeals, Wei Peng, Qian Huang, Bingjing Mao, Di Lun, Ekaterina Malova, Jazmyne V Simmons, Nick Carcioppolo

Faculty, Staff and Student Publications

Introduction: Guilt appeals are widely used as a persuasive approach in various areas of practice. However, the strength and direction of the persuasive effects of guilt appeals are mixed, which could be influenced by theoretical and methodological factors.

Method: The present study is a comprehensive meta-analysis of 26 studies using a random-effects model to assess the persuasive effects of guilt appeals. In total, 127 effect sizes from seven types of persuasive outcomes (i.e., guilt, attitude, behavior, behavioral intention, non-guilt emotions, motivation, and cognition) were calculated based on 7,512 participants.

Results: The analysis showed a small effect size of guilt appeals …

Sociodemographic Differences In Menthol Cigarette Use In The United States, Rajesh Talluri, Sanjay Shete

Faculty, Staff and Student Publications

Background: Menthol cigarette use is associated with higher smoking initiation and reduced smoking cessation. We investigated sociodemographic differences in menthol and nonmenthol cigarette use in the United States.

Methods: We used the most recent available data from the May 2019 wave of the nationally-representative Tobacco Use Supplement to the Current Population Survey. The survey weights were used to estimate the national prevalence of individuals who currently smoke among individuals who use menthol and nonmenthol cigarettes. Survey-weighted logistic regression methods were used to estimate the association of menthol cigarette use with formerly smoking cigarettes and attempting to quit within the past …

Applying Ht-Saxs To Chemical Ligand Screening, Chris A Brosey, Runze Shen, Davide Moiani, Darin E Jones, Kathryn Burnett, Greg L Hura, 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 …

Adverse Events Of Immune Checkpoint Therapy Alone Versus When Combined With Vascular Endothelial Growth Factor Inhibitors: A Pooled Meta-Analysis Of 1735 Patients, Iuliia Kovalenko, Wern Lynn Ng, Yimin Geng, Yinghong Wang, Pavlos Msaouel, Shailender Bhatia, Petros Grivas, Raed Benkhadra, Omar Alhalabi

Faculty, Staff and Student Publications

Background: Combining immune checkpoint therapy (ICT) and vascular endothelial growth factor inhibitors (VEGFi) may result in increased treatment-related and immune-related adverse events (TRAEs and irAEs) compared to ICT alone. This metanalysis was conducted to identify prospective phase II or III clinical studies that evaluated the toxicity profile of ICT + VEGFi compared to ICT alone.

Methods: A systematic search was performed across all cancer types and major databases until August 10, 2022, and screening was done by two independent investigators. Inclusion criteria included phase 2 or 3 studies with at least one arm of patients treated with combination therapy and …

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, Samantha Mota, Xuebo Chen, Tingting Mills, 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. …

Positron Emission Tomography Derived Metrics In Relapsed Or Refractory Large B-Cell Lymphoma With Residual Disease Before Autologous Stem Cell Transplant, Hua-Jay J Cherng, Guofan Xu, Lei Feng, Raphael Steiner, Luis Fayad, Paolo Strati, Ranjit Nair, Loretta J Nastoupil, Hun Ju Lee, Sattva S Neelapu, Christopher R Flowers, Maria Rodriguez, Michael Wang, Fredrick Hagemeister, Chelsea C Pinnix, Jeremy Ramdial, Samer Srour, Yago Nieto, Katayoun Rezvani, Richard Champlin, Partow Kebriaei, Jason Westin, Homer A Macapinlac, Elizabeth Shpall, Sairah Ahmed

Faculty, Staff and Student Publications

Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative treatment for patients with relapsed or refractory large B-cell lymphoma (rrLBCL) with chemosensitive disease. A18 F-fluorodeoxyglucose positron emission tomography (PET) scan after salvage chemotherapy is used to assess response and eligibility for ASCT, but metrics for chemosensitivity in patients with residual disease are not well defined. We performed a single-centre retrospective analysis of 92 patients with a partial response or stable disease after salvage chemotherapy for rrLBCL who received ASCT to investigate PET-derived parameters and their prognostic utility. The Deauville 5-point Scale (D-5PS) score, …

The Kynurenine Pathway Presents Multi-Faceted Metabolic Vulnerabilities In Cancer, Ricardo A León-Letelier, Rongzhang Dou, Jody Vykoukal, Ali Hussein Abdel Sater, Edwin Ostrin, Samir Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

The kynurenine pathway (KP) and associated catabolites play key roles in promoting tumor progression and modulating the host anti-tumor immune response. To date, considerable focus has been on the role of indoleamine 2,3-dioxygenase 1 (IDO1) and its catabolite, kynurenine (Kyn). However, increasing evidence has demonstrated that downstream KP enzymes and their associated metabolite products can also elicit tumor-microenvironment immune suppression. These advancements in our understanding of the tumor promotive role of the KP have led to the conception of novel therapeutic strategies to target the KP pathway for anti-cancer effects and reversal of immune escape. This review aims to 1) …