Medicine and Health Sciences Commons^™

Immunotherapy-Related Pneumonitis And The Synergic Impact Of Thoracic Radiation And Preexisting Interstitial Lung Disease, Maria Azhar, Rodeo Abrencillo, Saumil Gandhi, Mehmet Altan, Ajay Sheshadri

Faculty, Staff and Student Publications

PURPOSE OF REVIEW: Immune checkpoint inhibitors (ICIs) are the frontline of therapy for most cancers. Although ICIs are sometimes considered to be less harmful than systemic chemotherapies, ICIs may cause immune-related adverse events, which are cases of off-target inflammation in healthy tissues. Pneumonitis, an immune-related adverse event, is the leading cause of therapy-related mortality with ICIs. The aim of this review is to discuss how preexisting interstitial lung disease (ILD) and thoracic radiation increase the risk for ICI-pneumonitis. We discuss potential mechanisms of lung injury and how pneumonitis may impact cancer treatments.

RECENT FINDINGS: Preexisting ILD and thoracic radiation are …

Pulvinar Neuromodulation For Seizure Monitoring And Network Modulation In Temporal Plus Epilepsy, Yash Shashank Vakilna, Ganne Chaitanya, Muhammad Ubaid Hafeez, Adeel Ilyas, Manojkumar Saranathan, Jay Gavvala, Nitin Tandon, Sandipan Pati

Faculty, Staff and Student Publications

Deep brain stimulation (DBS) is a promising treatment for drug-refractory epilepsies (DRE) when targeting the anterior nuclei of thalamus (ANT). However, targeting other thalamic nuclei, such as the pulvinar, shows therapeutic promise. Our pioneering case study presents the application of ambulatory seizure monitoring using spectral fingerprinting (12.15-17.15 Hz) recorded through Medtronic Percept DBS implanted bilaterally in the medial pulvinar thalami. This technology offers unprecedented opportunities for real-time monitoring of seizure burden and thalamocortical network modulation for effective seizure reduction in patients with bilateral mesial temporal and temporal plus epilepsies that are not suitable for resection.

A Retrospective Study Of Cerebrolysin In Patients With Moderate To Severe Traumatic Brain Injury: Cognitive And Functional Outcomes, Claudio Soto, Pablo Salinas, Daniel Muñoz, Sandra Olivares, Javiera González, Virginia Sáez, Violeta Romero

Faculty, Staff and Student Publications

In this retrospective study, we aimed to evaluate the effects of the neurotrophic compound Cerebrolysin on executive, cognitive, and functional performance in patients with traumatic brain injury (TBI) with a highly severe disability level. A total of 44 patients were included in the study, with 33 patients in the control group and 11 patients in the interventional group who received intravenous infusions of 30 mL Cerebrolysin. Both groups received standard rehabilitation therapy following the rehabilitation protocol for patients with TBI at Hospital Clínico Mutual de Seguridad. Functional and cognitive scales were evaluated at baseline, at four months, and at the …

Transplantation Referral Patterns For Patients With Newly Diagnosed Higher-Risk Myelodysplastic Syndromes And Acute Myeloid Leukemia At Academic And Community Sites In The Connect® Myeloid Disease Registry: Potential Barriers To Care, Benjamin Tomlinson, Marcos De Lima, Christopher R Cogle, Michael A Thompson, David L Grinblatt, Daniel A Pollyea, Rami S Komrokji, Gail J Roboz, Michael R Savona, Mikkael A Sekeres, Mehrdad Abedi, Guillermo Garcia-Manero, Sandra E Kurtin, Jaroslaw P Maciejewski, Jay L Patel, Dennis A Revicki, Tracy I George, E Dawn Flick, Pavel Kiselev, Chrystal U Louis, Irene S Degutis, Melissa Nifenecker, Harry P Erba, David P Steensma, Bart L Scott

Faculty, Staff and Student Publications

Hematopoietic stem cell transplantation (HCT) is indicated for patients with higher-risk (HR) myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Age, performance status, patient frailty, comorbidities, and nonclinical factors (eg, cost, distance to site) are all recognized as important clinical factors that can influence HCT referral patterns and patient outcomes; however, the proportion of eligible patients referred for HCT in routine clinical practice is largely unknown. This study aimed to assess patterns of consideration for HCT among patients with HR-MDS and AML enrolled in the Connect® Myeloid Disease Registry at community/government (CO/GOV)- or academic (AC)-based sites, as well as to …

Nivolumab And Ipilimumab With Concurrent Stereotactic Radiosurgery For Intracranial Metastases From Non-Small Cell Lung Cancer: Analysis Of The Safety Cohort For Non-Randomized, Open-Label, Phase I/Ii Trial, Mehmet Altan, Yan Wang, Juhee Song, James Welsh, Chad Tang, Nandita Guha-Thakurta, George R Blumenschein, Brett W Carter, Jeffrey S Wefel, Amol J Ghia, Debra N Yeboa, Mary Frances Mcaleer, Caroline Chung, Kristina D Woodhouse, Susan L Mcgovern, Chenyang Wang, Betty Y S Kim, Jeffrey S Weinberg, Tina M Briere, Yasir Y Elamin, Xiuning Le, Tina Cascone, Marcelo V Negrao, Ferdinandos Skoulidis, Renata Ferrarotto, John V Heymach, Jing Li

Faculty, Staff and Student Publications

BACKGROUND: Up to 20% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), for which the current standard of care is radiation therapy with or without surgery. There are no prospective data on the safety of stereotactic radiosurgery (SRS) concurrent with immune checkpoint inhibitor therapy for BM. This is the safety cohort of the phase I/II investigator-initiated trial of SRS with nivolumab and ipilimumab for patients with BM from NSCLC.

PATIENTS AND METHODS: This single-institution study included patients with NSCLC with active BM amenable to SRS. Brain SRS and systemic therapy with nivolumab and ipilimumab were delivered …

Src Stimulates Abl-Dependent Phosphorylation Of The Guanine Exchange Factor Net1a To Promote Its Cytosolic Localization And Cell Motility, Ashabari Sprenger, Heather S Carr, Arzu Ulu, Jeffrey A Frost

Faculty, Staff and Student Publications

The neuroepithelial cell transforming gene 1 (Net1) is a guanine nucleotide exchange factor for the small GTPase RhoA that promotes cancer cell motility and metastasis. Two isoforms of Net1 exist, Net1 and Net1A, both of which are sequestered in the nucleus in quiescent cells to prevent aberrant RhoA activation. Many cell motility stimuli drive cytosolic relocalization of Net1A, but mechanisms controlling this event are not fully understood. Here, we demonstrate that epithelial growth factor stimulates protein kinase Src- and Abl1-dependent phosphorylation of Net1A to promote its cytosolic localization. We show that Abl1 efficiently phosphorylates Net1A on Y373, and that phenylalanine …

Endoscopic Mucosal Resection: Tips And Tricks For Gastrointestinal Trainees, Tessa Herman, Bryant Megna, Kumar Pallav, Mohammad Bilal

Faculty, Staff and Student Publications

Endoscopic mucosal resection (EMR) is a minimally invasive, specialized endoscopic technique that is useful in resecting superficial gastrointestinal lesions that are unable to be removed by standard polypectomy. This is typically accomplished using a submucosal injection that lifts the lesion away from the muscularis propria to allow for safe resection of the polyp, either via piecemeal or en bloc resection. Over the years, several techniques exist to perform EMR including conventional EMR or hot EMR, cold EMR and underwater EMR. Despite its established advantages and safety over conventional techniques such as surgery, the adoption of endoscopic resection (and thus the …

Therapeutic Potential Of Salicylamide Derivatives For Combating Viral Infections, Jimin Xu, Yu Xue, Andrew A Bolinger, Jun Li, Mingxiang Zhou, Haiying Chen, Hongmin Li, Jia Zhou

Faculty, Staff and Student Publications

Since time immemorial human beings have constantly been fighting against viral infections. The ongoing and devastating coronavirus disease 2019 pandemic represents one of the most severe and most significant public health emergencies in human history, highlighting an urgent need to develop broad-spectrum antiviral agents. Salicylamide (2-hydroxybenzamide) derivatives, represented by niclosamide and nitazoxanide, inhibit the replication of a broad range of RNA and DNA viruses such as flavivirus, influenza A virus, and coronavirus. Moreover, nitazoxanide was effective in clinical trials against different viral infections including diarrhea caused by rotavirus and norovirus, uncomplicated influenza A and B, hepatitis B, and hepatitis C. …

Venetoclax Consolidation In High-Risk Cll Treated With Ibrutinib For ≥1 Year Achieves A High Rate Of Undetectable Mrd, Philip A Thompson, Michael J Keating, Alessandra Ferrajoli, Nitin Jain, Christine B Peterson, Naveen Garg, Sa A Wang, Jeffrey L Jorgensen, Tapan M Kadia, Prithviraj Bose, Naveen Pemmaraju, Nicholas J Short, William G Wierda

Faculty, Staff and Student Publications

Patients receiving ibrutinib for CLL rarely achieve undetectable measurable residual disease (U-MRD), necessitating indefinite therapy, with cumulative risks of treatment discontinuation due to progression or adverse events. This study added venetoclax to ibrutinib for up to 2 years, in patients who had received ibrutinib for ≥12 months (mo) and had ≥1 high risk feature (TP53 mutation and/or deletion, ATM deletion, complex karyotype or persistently elevated β2-microglobulin). The primary endpoint was U-MRD with 10−4 sensitivity (U-MRD4) in bone marrow (BM) at 12mo. Forty-five patients were treated. On intention-to-treat analysis, 23/42 (55%) patients improved their response to CR (2 pts were …

Identification Of Unique Α4 Chain Structure And Conserved Antiangiogenic Activity Of Α3nc1 Type Iv Collagen In Zebrafish, Valerie S Lebleu, Jianli Dai, Susan Tsutakawa, Brian A Macdonald, Joseph L Alge, Malin Sund, Liang Xie, Hikaru Sugimoto, John Tainer, Leonard I Zon, Raghu Kalluri

Faculty, Staff and Student Publications

BACKGROUND: Type IV collagen is an abundant component of basement membranes in all multicellular species and is essential for the extracellular scaffold supporting tissue architecture and function. Lower organisms typically have two type IV collagen genes, encoding α1 and α2 chains, in contrast with the six genes in humans, encoding α1-α6 chains. The α chains assemble into trimeric protomers, the building blocks of the type IV collagen network. The detailed evolutionary conservation of type IV collagen network remains to be studied.

RESULTS: We report on the molecular evolution of type IV collagen genes. The zebrafish α4 non-collagenous (NC1) domain, in …

Characterization Of The Oral Microbiota Among Middle-Aged Men With And Without Human Papillomavirus Infection, Kristina R Dahlstrom, Andrew G Sikora, Yanhong Liu, Chia-Chi Chang, Peng Wei, Erich M Sturgis, Guojun Li

Faculty, Staff and Student Publications

OBJECTIVES: To characterize the oral microbiota among middle-aged men and identify differences between men with a prevalent oral high-risk (oncogenic) HPV infection and those without.

MATERIALS AND METHODS: This was a case-control study nested within a prospective screening study for HPV-related cancers among middle-aged men. 16S rRNA sequencing was used to characterize the oral microbiota and the cobas HPV Test was used to detect presence of oral high-risk HPV types. We determined the overall composition of the oral microbiota and assessed differences in relative abundance of bacterial taxa as well as alpha and beta diversity among men with a prevalent …

Proteogenomic Approaches For The Identification Of Nf1/Neurofibromin-Depleted Estrogen Receptor-Positive Breast Cancers For Targeted Treatment, Beom-Jun Kim, Ze-Yi Zheng, Jonathan T Lei, Matthew V Holt, Anran Chen, Jianheng Peng, Diana Fandino, Purba Singh, Hilda Kennedy, Yongchao Dou, María Del Rosario Chica-Parrado, Emmanuel Bikorimana, Dan Ye, Yunguan Wang, Ariella B Hanker, Nada Mohamed, Susan G Hilsenbeck, Bora Lim, Jaya Ruth Asirvatham, Arun Sreekumar, Bing Zhang, George Miles, Meenakshi Anurag, Matthew J Ellis, Eric C Chang

Faculty, Staff and Student Publications

NF1 is a key tumor suppressor that represses both RAS and estrogen receptor-α (ER) signaling in breast cancer. Blocking both pathways by fulvestrant (F), a selective ER degrader, together with binimetinib (B), a MEK inhibitor, promotes tumor regression in NF1-depleted ER+ models. We aimed to establish approaches to determine how NF1 protein levels impact B+F treatment response to improve our ability to identify B+F sensitive tumors. We examined a panel of ER+ patient-derived xenograft (PDX) models by DNA and mRNA sequencing and found that more than half of these models carried an NF1 shallow deletion and generally have low mRNA …

Multi-Center Validation Of The Mcgovern Pediatric Blunt Cerebrovascular Injury Screening Score, Sidish S Venkataraman, Joseph P Herbert, Vijay M Ravindra, Bangning N Yu, Robert J Bollo, Charles S Cox, Stephen R Gannon, David D Limbrick, Robert P Naftel, Irma T Ugalde, Brian K Yorkgitis, Howard L Weiner, Manish N Shah

Faculty, Staff and Student Publications

Blunt cerebrovascular injury (BCVI) is defined as blunt trauma to the head and neck leading to damage to the vertebral and/or carotid arteries; debate exists regarding which children are considered at high risk for BCVI and in need of angiographic/vessel imaging. We previously proposed a screening tool, the McGovern score, to identify pediatric trauma patients at high risk for BCVI, and we aim to validate the McGovern score by pooling data from multiple pediatric trauma centers. This is a multi-center, hospital-based, cohort study from all prospectively registered pediatric (age) trauma patients who presented to the emergency department (ED) between 2003 …

Single-Cell Profiling Of Tumor Immune Microenvironment Reveals Immune Irresponsiveness In Gastric Signet-Ring Cell Carcinoma, Jing Chen, Kuai Liu, Yikai Luo, Muxing Kang, Jun Wang, Guofeng Chen, Jia Qi, Wenxuan Wu, Beidi Wang, Yaxuan Han, Le Shi, Kefan Wang, Xiaying Han, Xiaojing Ma, Wei Liu, Yuan Ding, Liangjing Wang, Han Liang, Lie Wang, Jian Chen

Faculty, Staff and Student Publications

Background & aims: Gastric cancer (GC) is a major cancer type characterized by high heterogeneity in both tumor cells and the tumor immune microenvironment (TIME). One intractable GC subtype is gastric signet-ring cell carcinoma (GSRCC), which is associated with poor prognosis. However, it remains unclear what the GSRCC TIME characteristics are and how these characteristics may contribute to clinical outcomes.

Methods: We enrolled 32 patients with advanced GC of diverse subtypes and profiled their TIME using an immune-targeted single-cell profiling strategy, including (1) immune-targeted single-cell RNA sequencing (n = 20 patients) and (2) protein expression profiling by a targeted antibody …

Proteomic Analysis Identifies Circulating Proteins Associated With Plasma Amyloid-Β And Incident Dementia, Adrienne Tin, Kevin J Sullivan, Keenan A Walker, Jan Bressler, Rajesh Talluri, Bing Yu, Jeanette Simino, Valborg Gudmundsdottir, Valur Emilsson, Lori L Jennings, Lenore Launer, Hao Mei, Eric Boerwinkle, B Gwen Windham, Rebecca Gottesman, Vilmundur Gudnason, Josef Coresh, Myriam Fornage, Thomas H Mosley

Faculty, Staff and Student Publications

BACKGROUND: Plasma amyloid-β (Aβ) (Aβ

METHODS: We analyzed the association of these 3 plasma Aβ measures with 4638 circulating proteins among a subset of the participants of the Atherosclerosis Risk in Communities (ARIC) study (midlife:

RESULTS: At midlife, of the 296 Aβ-associated proteins, 8 were associated with incident dementia from midlife and late life in the ARIC study, and NPPB, IBSP, and THBS2 were replicated in the AGES-Reykjavik Study. At late life, of the 34 Aβ-associated proteins, none were associated with incident dementia at midlife, and kidney function explained 10%, 12%, and 0.2% of the variance of Aβ

CONCLUSIONS: This …

Free Ferrous Ions Sustain Activity Of Mammalian Stearoyl-Coa Desaturase-1, Jiemin Shen, Gang Wu, Brad S Pierce, Ah-Lim Tsai, Ming Zhou

Faculty, Staff and Student Publications

Mammalian stearoyl-CoA desaturase-1 (SCD1) introduces a double-bond to a saturated long-chain fatty acid in a reaction catalyzed by a diiron center. The diiron center is well-coordinated by conserved histidine residues and is thought to remain with the enzyme. However, we find here that SCD1 progressively loses its activity during catalysis and becomes fully inactive after about nine turnovers. Further studies show that the inactivation of SCD1 is due to the loss of an iron (Fe) ion in the diiron center and that the addition of free ferrous ions (Fe

Predictors Of Self-Reported General Health Status In People Experiencing Homelessness With Serious Mental Illness, Landon Presnall, Robert Suchting, Gaybrielle Hicks, Jane Hamilton

Faculty, Staff and Student Publications

PURPOSE: The growing homeless population in the U.S.A. is disproportionately impacted by poor mental and physical health status, including a higher incidence of acute and chronic health problems, increased hospitalizations, and premature mortality compared to the general population. This study examined the association between demographic, social, and clinical factors and perceptions of general health status among the homeless population during admission to an integrated behavioral health treatment program.

METHODS: The study sample included 331 adults experiencing homelessness with a serious mental illness or co-occurring disorder. Participants were enrolled in services at a day program for unsheltered homeless adults, a residential …

Predicting Benefit From Immune Checkpoint Inhibitors In Patients With Non-Small-Cell Lung Cancer By Ct-Based Ensemble Deep Learning: A Retrospective Study, Maliazurina B Saad, Lingzhi Hong, Muhammad Aminu, Natalie I Vokes, Pingjun Chen, Morteza Salehjahromi, Kang Qin, Sheeba J Sujit, Xuetao Lu, Elliana Young, Qasem Al-Tashi, Rizwan Qureshi, Carol C Wu, Brett W Carter, Steven H Lin, Percy P Lee, Saumil Gandhi, Joe Y Chang, Ruijiang Li, Michael F Gensheimer, Heather A Wakelee, Joel W Neal, Hyun-Sung Lee, Chao Cheng, Vamsidhar Velcheti, Yanyan Lou, Milena Petranovic, Waree Rinsurongkawong, Xiuning Le, Vadeerat Rinsurongkawong, Amy Spelman, Yasir Y Elamin, Marcelo V Negrao, Ferdinandos Skoulidis, Carl M Gay, Tina Cascone, Mara B Antonoff, Boris Sepesi, Jeff Lewis, Ignacio I Wistuba, John D Hazle, Caroline Chung, David Jaffray, Don L Gibbons, Ara Vaporciyan, J Jack Lee, John V Heymach, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

BACKGROUND: Only around 20-30% of patients with non-small-cell lung cancer (NCSLC) have durable benefit from immune-checkpoint inhibitors. Although tissue-based biomarkers (eg, PD-L1) are limited by suboptimal performance, tissue availability, and tumour heterogeneity, radiographic images might holistically capture the underlying cancer biology. We aimed to investigate the application of deep learning on chest CT scans to derive an imaging signature of response to immune checkpoint inhibitors and evaluate its added value in the clinical context.

METHODS: In this retrospective modelling study, 976 patients with metastatic, EGFR/ALK negative NSCLC treated with immune checkpoint inhibitors at MD Anderson and Stanford were enrolled from …

Privacy Preserving Identification Of Population Stratification For Collaborative Genomic Research, Leonard Dervishi, Wenbiao Li, Anisa Halimi, Xiaoqian Jiang, Jaideep Vaidya, Erman Ayday

Faculty, Staff and Student Publications

The rapid improvements in genomic sequencing technology have led to the proliferation of locally collected genomic datasets. Given the sensitivity of genomic data, it is crucial to conduct collaborative studies while preserving the privacy of the individuals. However, before starting any collaborative research effort, the quality of the data needs to be assessed. One of the essential steps of the quality control process is population stratification: identifying the presence of genetic difference in individuals due to subpopulations. One of the common methods used to group genomes of individuals based on ancestry is principal component analysis (PCA). In this article, we …

Development Of Photo-Polymerization-Type 3d Printer For High-Viscosity Ceramic Resin Using Cnn-Based Surface Defect Detection, Jin-Kyo Chung, Jeong-Seon Im, Min-Soo Park

Faculty, Staff and Student Publications

Due to the high hardness and brittleness of ceramic materials, conventional cutting methods result in poor quality and machining difficulties. Additive manufacturing has also been tried in various ways, but it has many limitations. This study aims to propose a system to monitor surface defects that occur during the printing process based on high-viscosity composite resin that maximizes ceramic powder content in real time using image processing and convolutional neural network (CNN) algorithms. To do so, defects mainly observed on the surface were classified into four types by form: pore, minor, critical, and error, and the effect of each defect …

Innovations In Cell Therapy In Pediatric Diseases: A Narrative Review, Razan El Sayed, Karan Michael Shankar, Atharwa Rajan Mankame, Charles S Cox

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVE: Stem cell therapy is a regenerative medicine modality that has the potential to decrease morbidity and mortality by promoting tissue regeneration or modulating the inflammatory response. An increase in the number of clinical trials investigating the efficacy and safety of stem cell therapy in pediatric diseases has led to advancements in this field. Currently, multiple sources and types of stem cells have been utilized in the treatment of pediatric diseases. This review aims to inform researchers and clinicians about preclinical and clinical stem cell therapy trials in pediatric patients. We discuss the different types of stem cells …

Stimulatory Effects Of Lycium Shawii On Human Melanocyte Proliferation, Migration, And Melanogenesis: In Vitro And In Silico Studies, Karen E Gerlach, Kanchan Ashok Phalak, Ethan O Cohen, Kiran N Chang, Roland Bassett, Gary J Whitman

Faculty, Staff and Student Publications

Rationale and objectives: Information evaluating the efficacy of 2D synthesized mammography (2Ds) reconstructions in microcalcification detection is limited. This study used stereotactic biopsy data for microcalcifications to evaluate the stepwise implementation of 2Ds in screening mammography. The study aim was to identify whether 2Ds + digital breast tomosynthesis (DBT) is non-inferior to 2D digital mammography (2DM) + 2Ds + DBT, 2DM + DBT, and 2DM in identifying microcalcifications undergoing further diagnostic imaging and stereotactic biopsy.

Materials and methods: Retrospective stereotactic biopsy data were extracted following 151,736 screening mammograms of healthy women (average age, 56.3 years; range, 30-89 years), performed between …

Co-Targeting Fasn And Mtor Suppresses Uveal Melanoma Growth, Anna Han, Dzmitry Mukha, Vivian Chua, Timothy J Purwin, Manoela Tiago, Bhavik Modasia, Usman Baqai, Jenna L Aumiller, Nelisa Bechtel, Emily Hunter, Meggie Danielson, Mizue Terai, Philip B Wedegaertner, Takami Sato, Solange Landreville, Michael A Davies, Stefan Kurtenbach, J William Harbour, Zachary T Schug, Andrew E Aplin

Faculty, Staff and Student Publications

Uveal melanoma (UM) displays a high frequency of metastasis; however, effective therapies for metastatic UM are limited. Identifying unique metabolic features of UM may provide a potential targeting strategy. A lipid metabolism protein expression signature was induced in a normal choroidal melanocyte (NCM) line transduced with GNAQ (Q209L), a driver in UM growth and development. Consistently, UM cells expressed elevated levels of fatty acid synthase (FASN) compared to NCMs. FASN upregulation was associated with increased mammalian target of rapamycin (mTOR) activation and sterol regulatory element-binding protein 1 (SREBP1) levels. FASN and mTOR inhibitors alone significantly reduced UM cell growth. Concurrent …

Ndufs4 Regulates Cristae Remodeling In Diabetic Kidney Disease, Koki Mise, Jianyin Long, Daniel L Galvan, Zengchun Ye, Guizhen Fan, Irina I Serysheva, Travis I Moore, Jun Wada, Paul T Schumacker, Benny H Chang, Farhad R Danesh

Faculty, Staff and Student Publications

The mitochondrial electron transport chain (ETC) is a highly adaptive process to meet metabolic demands of the cell, and its dysregulation has been associated with diverse clinical pathologies. However, the role and nature of impaired ETC in kidney diseases remains poorly understood. Here, we generated diabetic mice with podocyte-specific overexpression of Ndufs4, an accessory subunit of mitochondrial complex I, as a model to investigate the role of ETC integrity in diabetic kidney disease (DKD). We find that these conditional mice exhibit significant improvements in cristae morphology, mitochondrial dynamics, and albuminuria. By coupling proximity labeling with super-resolution imaging, we also identify …

A Phase I Study Of Milademetan (Ds3032b) In Combination With Low Dose Cytarabine With Or Without Venetoclax In Acute Myeloid Leukemia: Clinical Safety, Efficacy, And Correlative Analysis, Jayastu Senapati, Muharrem Muftuoglu, Jo Ishizawa, Hussein A Abbas, Sanam Loghavi, Gautam Borthakur, Musa Yilmaz, Ghayas C Issa, Samuel I Dara, Mahesh Basyal, Li Li, Kiran Naqvi, Rasoul Pourebrahim, Elias J Jabbour, Steven M Kornblau, Nicholas J Short, Naveen Pemmaraju, Guillermo Garcia-Manero, Farhad Ravandi, Joseph Khoury, Naval Daver, Hagop M Kantarjian, Michael Andreeff, Courtney D Dinardo

Faculty, Staff and Student Publications

In TP53 wild-type acute myeloid leukemia (AML), inhibition of MDM2 can enhance p53 protein expression and potentiate leukemic cell apoptosis. MDM2 inhibitor (MDM2i) monotherapy in AML has shown modest responses in clinical trials but combining options of MDM2i with other potent AML-directed agents like cytarabine and venetoclax could improve its efficacy. We conducted a phase I clinical trial (NCT03634228) to study the safety and efficacy of milademetan (an MDM2i) with low-dose cytarabine (LDAC)±venetoclax in adult patients with relapsed refractory (R/R) or newly diagnosed (ND; unfit) TP53 wild-type AML and performed comprehensive CyTOF analyses to interrogate multiple signaling pathways, the p53-MDM2 …

A Systematic Review Of Interventions To Promote Hpv Vaccination Globally, Cam Escoffery, Courtney Petagna, Christine Agnone, Stephen Perez, Lindsay B Saber, Grace Ryan, Meena Dhir, Swathi Sekar, Katherine A Yeager, Caitlin B Biddell, Purnima Madhivanan, Stephanie Lee, Amanda S English, Lara Savas, Eliza Daly, Thuy Vu, Maria E Fernandez

Faculty, Staff and Student Publications

BACKGROUND: Despite the human papillomavirus (HPV) vaccine being a safe, effective cancer prevention method, its uptake is suboptimal in the United States (U.S.). Previous research has found a variety of intervention strategies (environmental and behavioral) to increase its uptake. The purpose of the study is to systematically review the literature on interventions that promote HPV vaccination from 2015 to 2020.

METHODS: We updated a systematic review of interventions to promote HPV vaccine uptake globally. We ran keyword searches in six bibliographic databases. Target audience, design, level of intervention, components and outcomes were abstracted from the full-text articles in Excel databases. …

A Phase I Study Of Milademetan (Ds3032b) In Combination With Low Dose Cytarabine With Or Without Venetoclax In Acute Myeloid Leukemia: Clinical Safety, Efficacy, And Correlative Analysis, Jayastu Senapati, Muharrem Muftuoglu, Jo Ishizawa, Hussein A Abbas, Sanam Loghavi, Gautam Borthakur, Musa Yilmaz, Ghayas C Issa, Samuel I Dara, Mahesh Basyal, Li Li, Kiran Naqvi, Rasoul Pourebrahim, Elias J Jabbour, Steven M Kornblau, Nicholas J Short, Naveen Pemmaraju, Guillermo Garcia-Manero, Farhad Ravandi, Joseph Khoury, Naval Daver, Hagop M Kantarjian, Michael Andreeff, Courtney D Dinardo

Faculty, Staff and Student Publications

In TP53 wild-type acute myeloid leukemia (AML), inhibition of MDM2 can enhance p53 protein expression and potentiate leukemic cell apoptosis. MDM2 inhibitor (MDM2i) monotherapy in AML has shown modest responses in clinical trials but combining options of MDM2i with other potent AML-directed agents like cytarabine and venetoclax could improve its efficacy. We conducted a phase I clinical trial (NCT03634228) to study the safety and efficacy of milademetan (an MDM2i) with low-dose cytarabine (LDAC)±venetoclax in adult patients with relapsed refractory (R/R) or newly diagnosed (ND; unfit) TP53 wild-type AML and performed comprehensive CyTOF analyses to interrogate multiple signaling pathways, …

G Protein-Coupled Receptor-Targeting Antibody-Drug Conjugates: Current Status And Future Directions, Peyton High, Kendra S Carmon

Faculty, Staff and Student Publications

In recent years, antibody-drug conjugates (ADCs) have emerged as promising anti-cancer therapeutic agents with several having already received market approval for the treatment of solid tumor and hematological malignancies. As ADC technology continues to improve and the range of indications treatable by ADCs increases, the repertoire of target antigens has expanded and will undoubtedly continue to grow. G protein-coupled receptors (GPCRs) are well-characterized therapeutic targets implicated in many human pathologies, including cancer, and represent a promising emerging target of ADCs. In this review, we will discuss the past and present therapeutic targeting of GPCRs and describe ADCs as therapeutic modalities. …

A Novel Peptide 'T14' Reflects Age And Photo-Aging In Human Skin, Sheila Rocha, Sara Garcia Ratés, Tumisang Moswete, Kristopher Kalleberg, Anna Villa, Jason P Harcup, Susan A Greenfield

Faculty, Staff and Student Publications

T14 is a 14mer peptide derived from the C-terminus of acetylcholinesterase (AChE). Once cleaved, it is independently bioactive of the parent molecule and enhances calcium influx in different cell types, in a range of scenarios: it binds to an allosteric site selectively on the alpha-7 receptor, where it modulates calcium influx and is thus a potential trophic agent, as already reported in a range of normal developmental scenarios. However, if inappropriately activated, this erstwhile beneficial effect converts to a toxic one, resulting in pathologies as disparate as Alzheimer’s and various metastatic cancers. Given that epidermal keratinocyte cells have the same …

Chronic Social Defeat Alters Brain Vascular-Associated Cell Gene Expression Patterns Leading To Vascular Dysfunction And Immune System Activation, Joshua D Samuels, Madison L Lotstein, Michael L Lehmann, Abdel G Elkahloun, Subhadra Banerjee, Miles Herkenham

Faculty, Staff and Student Publications

Brain vascular integrity is critical for brain health, and its disruption is implicated in many brain pathologies, including psychiatric disorders. Brain-vascular barriers are a complex cellular landscape composed of endothelial, glial, mural, and immune cells. Yet currently, little is known about these brain vascular-associated cells (BVACs) in health and disease. Previously, we demonstrated that 14 days of chronic social defeat (CSD), a mouse paradigm that produces anxiety and depressive-like behaviors, causes cerebrovascular damage in the form of scattered microbleeds. Here, we developed a technique to isolate barrier-related cells from the mouse brain and subjected the isolated cells to single-cell RNA …