Medicine and Health Sciences Commons^™

Using Audacity Software To Enhance Teaching And Learning Of Hearing Science Course: A Tutorial, Nilesh Washnik, Chandan Suresh, Chao-Yang Lee

Teaching and Learning in Communication Sciences & Disorders

Audacity is a multi-platform free, open-source audio recorder and editor software. The advantage of Audacity software is as follows: easy installation and simple visual interface, no registrations or hardware requirements, and availability at no cost might make it a preferred software to carry out class demonstrations and lab activities for an undergraduate course in the Communication Sciences and Disorders discipline. The tutorial aims to illustrate how Audacity software can be used to demonstrate various psychoacoustic phenomena commonly taught in undergraduate Hearing Science courses. This tutorial is divided into fundamental and advanced concepts from the pedagogy and student learning standpoint. The …

Knowledge And Perceptions Of Slp Graduate Students Regarding Multiculturalism, Evy Jewell Hayes, Laura Amanda Mathews

Teaching and Learning in Communication Sciences & Disorders

Populations in the United States rise daily, as do the number of people who are considered multicultural. With this comes a greater need for speech-language pathologists (SLPs) who are able to assess and treat such individuals – a training process that begins in graduate programs. The primary objective of this study was to determine the knowledge and perceptions of graduate students in speech-language pathology as it pertains to multiculturalism. A survey was conducted to explore graduate students’ knowledge and perceptions of multicultural topics. Participants were recruited from programs in the southeastern United States via email. Just under 400 surveys were …

Can The Use Of Art And Active Learning Improve Retention And Observational Skill Confidence Among Audiology Graduate Students, Aurora Weaver, Ashlyn Wheat, Travis Riffle, Chelsea Powell, Lindsey Leonard, Ryleigh Prickett, Anna Hill, Larry Molt

Teaching and Learning in Communication Sciences & Disorders

Human anatomy and physiology is considered one of the most difficult courses a student can take in a pre-health professional major in the US (Slominski, et. al., 2017). Research has revealed benefits of the use of art and anatomy within medical education, including improved clinical observational skills, greater understanding of disease and patient perspectives, and greater ability to empathize (Bell & Evans, 2014). Bell and Evans (2014) argue that observational skills are often overlooked in medical education. Use of art assignments in a graduate anatomy and physiology course will be discussed with reference to design and learning outcomes. The purpose …

Synthesis And Investigation Into The Estrogen Receptor Antagonist Activity Of Isoflavans And Their Synthetic Derivatives, Nikiwe N. Tsipa, Catherine H. Kaschula, Willem Van Otterlo, Amanda Swart

Research Symposium

Background: Breast cancer (BC) is the most invasive and prevalent cancer in women in South Africa, with numbers as high as 1 in 8 women in urban areas and with a large percentage being ER-positive (ER+). ER+ BC cells are reliant on the binding of the natural ligand 17β-estradiol (E2) to ERα and ERβ isoforms which drives tumor growth1. ER antagonists and inhibitors of estrogen synthesis are therefore widely used therapeutic agents in the treatment of BC. Isoflavans are natural products found in many dietary plants. They are phytoestrogens, able to act as natural anti-breast cancer agents, acting as ER …

Tertiary Drug Information Sources For Treatment And Prevention Of Covid-19., Robert D. Beckett, Yashawna Brattain, Judy Truong, Genevieve Engle

Parkview Pharmacy Department

OBJECTIVE: To evaluate tertiary drug information databases in terms of scope, consistency of content, and completeness of COVID-19 drug information.

METHODS: Five electronic drug information databases: Clinical Pharmacology, Lexi-Drugs, AHFS DI (American Hospital Formulary Service Drug Information), eFacts and Comparisons, and Micromedex In-Depth Answers, were evaluated in this cross-sectional evaluation study, with data gathered from October 2021 through February 2022. Two study investigators independently extracted data (parallel extraction) from each resource. Descriptive statistics were primarily used to evaluate scope (i.e., whether the resource addresses use of the medication for treatment or prevention of COVID-19) and completeness of content (i.e., whether …

A Multi-Modal Imaging Analysis Of Inter-Community Hub Nodes In Subjective Cognitive Decline Linking Longitudinal Hub Function Disruption To White Matter Integrity Kurtosis, Duncan Nowling

MUSC Theses and Dissertations

Subjective Cognitive Decline (SCD) has garnered much interest as a potential identifiable preclinical stage and indicator of risk for cognitive decline in Alzheimer’s Disease and related dementias (ADRD). Identification of individuals in this stage though is difficult, as they present with objectively normal cognitive evaluation scores, relying instead upon self-report of concern about decline in cognitive abilities. The use of non-invasive in-vivo imaging methods like BOLD functional imaging and diffusion tensor have allowed for complex mapping of both the functional and structural network features unique to this condition. This study furthers this network biomarker map of SCD by investigating the …

Intouch Week Of October 2, 2023, New York Medical College

InTouch

• Founder's Dinner 2023
• Explore NYMC Through the Eyes of Our 2023-2024 Social Media Ambassadors
• Bench-to-Bedside Seminar Series: Translational Inhalation Drug Delivery – Development of Inhaled Biologics
• Meet the President of NYMC Student Health Care Executives

Making Decisions "In The Dark": Learning Through Uncertainty In Clinical Practice During Covid-19, Urvashi Vaid, Henriette Lundgren, Karen E. Watkins, Deborah Ziring, Grace A. Alcid, Victoria J. Marsick, Dimitrios Papanagnou

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

PURPOSE: The purpose of this study was to explore how decision making and informal and incidental learning (IIL) emerged in the clinical learning environment (CLE) during the height of the Covid-19 pandemic. The authors' specific interest was to better understand the IIL that took place among frontline physicians who had to navigate a CLE replete with uncertainty and complexity with the future goal of creating experiences for medical students that would simulate IIL and use uncertainty as a catalyst for learning.

METHOD: Using a modified constructivist, grounded theory approach, we describe physicians' IIL while working during times of heightened uncertainty. …

10.02.2023 Orsp Connect, Liz Williamson

ORED Newsletter

No abstract provided.

Comparison Of Bacterial Culture With Biofire® Filmarray® Multiplex Pcr Screening Of Archived Cerebrospinal Fluid Specimens From Children With Suspected Bacterial Meningitis In Nigeria, S Obaro, F Hassan-Hanga, N Medugu, Rasaq Olaosebikan, G Olanipekun, B Jibir, S Gambo, Theresa Ajose, Carissa Duru, B Ebruke, H D Davies

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Diagnosis of bacterial meningitis remains a challenge in most developing countries due to low yield from bacterial culture, widespread use of non-prescription antibiotics, and weak microbiology laboratories. The objective of this study was to compare the yield from standard bacterial culture with the multiplex nested PCR platform, the BioFire® FilmArray® Meningitis/Encephalitis Panel (BioFire ME Panel), for cases with suspected acute bacterial meningitis.

METHODS: Following Gram stain and bacterial culture on cerebrospinal fluid (CSF) collected from children aged less than 5 years with a clinical suspicion of acute bacterial meningitis (ABM) as defined by the WHO guidelines, residual CSF specimens …

Kinome Reprogramming Is A Targetable Vulnerability In Esr1 Fusion-Driven Breast Cancer, Xuxu Gou, Shunqiang Li, Et Al.

2020-Current year OA Pubs

UNLABELLED: Transcriptionally active ESR1 fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs are not directly druggable because the C-terminal estrogen/anti-estrogen-binding domain is replaced with translocated in-frame partner gene sequences that confer constitutive transactivation. To discover alternative treatments, a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) was deployed to identify druggable kinases that are upregulated by diverse ESR1-TAFs. Subsequent explorations of drug sensitivity validated RET kinase as a common therapeutic vulnerability despite remarkable ESR1-TAF C-terminal sequence and structural diversity. Organoids and xenografts from a pan-ET-resistant patient-derived xenograft model that harbors the ESR1-e6>YAP1 TAF …

Reduction Of Sparc Protects Mice Against Nlrp3 Inflammasome Activation And Obesity, Seungjin Ryu, Olga Spadaro, Sviatoslav Sidorov, Aileen H. Lee, Sonia Caprio, Christopher Morrison, Steven R. Smith, Eric Ravussin, Irina Shchukina, Maxim N. Artyomov, Yun-Hee Youm, Vishwa Deep Dixit

2020-Current year OA Pubs

The comprehensive assessment of long-term effects of reducing intake of energy (CALERIE-II; NCT00427193) clinical trial established that caloric restriction (CR) in humans lowers inflammation. The identity and mechanism of endogenous CR-mimetics that can be deployed to control obesity-associated inflammation and diseases are not well understood. Our studies have found that 2 years of 14% sustained CR in humans inhibits the expression of the matricellular protein, secreted protein acidic and rich in cysteine (SPARC), in adipose tissue. In mice, adipose tissue remodeling caused by weight loss through CR and low-protein diet feeding decreased, while high-fat diet-induced (HFD-induced) obesity increased SPARC expression …

Safety And Immunogenicity Of Live Viral Vaccines In A Multicenter Cohort Of Pediatric Transplant Recipients, Amy G Feldman, Stacy Postma, Janis Stoll, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions.

OBJECTIVE: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody …

Tipifarnib Potentiates The Antitumor Effects Of Pi3kα Inhibition In Pik3ca- And Hras-Dysregulated Hnscc Via Convergent Inhibition Of Mtor Activity, Alison E Smith, Douglas R Adkins, Et Al.

2020-Current year OA Pubs

UNLABELLED: Outcomes for patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) are poor, with median overall survival (OS) ranging from 6 to 18 months. For those who progress on standard-of-care (chemo)immunotherapy, treatment options are limited, necessitating the development of rational therapeutic strategies. Toward this end, we targeted the key HNSCC drivers PI3K-mTOR and HRAS via the combination of tipifarnib, a farnesyltransferase (FTase) inhibitor, and alpelisib, a PI3Kα inhibitor, in multiple molecularly defined subsets of HNSCC. Tipifarnib synergized with alpelisib at the level of mTOR in PI3Kα- or HRAS-dependent HNSCCs, leading to marked cytotoxicity in vitro and tumor …

Alvin J. Siteman Cancer Center: Cancer Prevention Perspective, Graham A Colditz, Bettina F Drake, Timothy J Eberlein

2020-Current year OA Pubs

We summarize Siteman Cancer Center catchment that covers 82 counties in southern Illinois and eastern Missouri. We note both the high poverty and cancer rates in many rural counties. Siteman Community Outreach and Engagement has developed a number of strategies to move towards achieving health equity. These include NCI-funded research projects in rural clinics and outreach to improve access to cancer prevention services. To increase capacity for community-engaged research, we have developed and refined a Community Research Fellows Training Program.

Pre-Radiotherapy Ctdna Liquid Biopsy For Risk Stratification Of Oligometastatic Non-Small Cell Lung Cancer, Nicholas P Semenkovich, Shahed N Badiyan, Pamela P Samson, Hayley B Stowe, Yun E Wang, Rachel Star, Siddhartha Devarakonda, Ramaswamy Govindan, Saiama N Waqar, Clifford G Robinson, Gregory Vlacich, Bruna Pellini, Aadel A Chaudhuri

2020-Current year OA Pubs

The optimal treatment paradigm for patients with oligometastatic non-small cell lung cancer (NSCLC) remains unclear. Some patients with oligometastatic disease experience prolonged remission after locally consolidative radiation therapy (RT), while others harbor micrometastatic disease (below limits of detection by imaging) and benefit from systemic therapy. To risk-stratify and identify the patients most likely to benefit from locally consolidative RT, we performed a multi-institutional cohort study of 1487 patients with oligometastatic NSCLC undergoing liquid biopsy analysis of circulating tumor DNA (ctDNA). In total, 1880 liquid biopsies were performed and approximately 20% of patients (n = 309) had ctDNA measured prior to …

Safety And Immunogenicity Of Live Viral Vaccines In A Multicenter Cohort Of Pediatric Transplant Recipients, Amy G Feldman, Brenda L Beaty, Jose A Ferrolino, Gabriela Maron, Hillary K Weidner, Saira A Ali, Leandra Bitterfeld, Mary Alice Boulware, Kathleen M Campbell, Emily Carr, Shelley Chapman, Yeh-Chung Chang, Ryan Cunningham, Ronald H Dallas, Keerti L Dantuluri, Bryanna N Domenick, Noelle H Ebel, Scott Elisofon, Rima Fawaz, Marc Foca, Hayley A Gans, Vani V Gopalareddy, Cindy Gu, Nitika A Gupta, Katherine Harmann, Jessica Hollenbeck, Anna R Huppler, Catalina Jaramillo, Nagraj Kasi, Nanda Kerkar, Stacee Lerret, Steven J Lobritto, Maclovio J Lopez, Elizabeth Marini, Alisha Mavis, Sonia Mehra, Lynnette Moats, Sindhu Mohandas, Flor M Munoz, Krupa R Mysore, Ceren Onsan, Nadia Ovchinsky, Kerrigan Perkins, Stacy Postma, Lauren Pratscher, Elizabeth B Rand, Regina K Rowe, Danielle Schultz, Katherine Sear, Megan L Sell, Tanvi Sharma, Janis Stoll, Mychoua Vang, Dominique Villarin, Carly Weaver, Phoebe Wood, Olivia Woodford-Berry, George Yanni, Lara A Danziger-Isakov

Faculty, Staff and Students Publications

IMPORTANCE: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions.

OBJECTIVE: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody …

Symptomatic Obstructive Hydrocephalus Caused By Choroid Plexus Hyperplasia In A Pediatric Patient: Illustrative Case, Ana Sofia Alvarez, John P Mcginnis, Rajan Patel, Howard L Weiner

Faculty, Staff and Students Publications

BACKGROUND: Choroid plexus hyperplasia has been described as a rare cause of communicating hydrocephalus due to cerebrospinal fluid (CSF) overproduction. However, this is the first report of symptomatic obstructive hydrocephalus caused by mechanical obstruction of the aqueduct by a hyperplastic choroid plexus.

OBSERVATIONS: A 4-year-old male presented with headaches and intermittent emesis. Magnetic resonance imaging (MRI) of the brain showed abnormal enlargement of the choroid plexus in the lateral ventricles with extension into the third ventricle, resulting in obstruction of the aqueduct of Sylvius, leading to obstructive hydrocephalus. Endoscopic third ventriculostomy (ETV) was chosen as the surgical treatment. During the …

Heterocyclic Merging Of Stereochemically Diverse Chiral Piperazines And Morpholines With Indazoles, Amol B Viveki, Timothy M Mansfield, Kevin A Tran, Evan Lenkeit, Kevin R Mackenzie, Damian W Young, Srinivas Chamakuri

Faculty, Staff and Students Publications

We report a heterocyclic merging approach to construct novel indazolo-piperazines and indazolo-morpholines. Starting from chiral diamines and amino alcohols, novel regiochemically (1,3 and 1,4) and stereochemically diverse (relative and absolute) cohorts of indazolo-piperazines and indazolo-morpholines were obtained within six or seven steps. The key transformations involved are a Smiles rearrangement to generate the indazole core structure and a late-stage Michael addition to build the piperazine and morpholine heterocycles. We further explored additional vector diversity by incorporating substitutions on the indazole aromatic ring, generating a total of 20 unique, enantiomerically pure heterocyclic scaffolds.

Heritable Traits And Lung Cancer Risk: A Two-Sample Mendelian Randomization Study, Rowland W Pettit, Jinyoung Byun, Younghun Han, Quinn T Ostrom, Cristian Coarfa, Melissa L Bondy, Christopher I Amos

Faculty, Staff and Students Publications

INTRODUCTION: Lung cancer is a complex polygenic disorder. Analysis with Mendelian randomization (MR) allows for genetically predicted risks to be estimated between exposures and outcomes.

METHODS: We analyzed 345 heritable traits from the United Kingdom Biobank and estimated their associated effects on lung cancer outcomes using two sample MR. In addition to estimating effects with overall lung cancer, adenocarcinoma, small cell lung cancer, and squamous cell lung cancers, we performed conditional effect modeling with multivariate MR (MVMR) and the traits of alcohol use, smoking initiation, average pre-tax income, and educational attainment.

RESULTS: Univariate MR provided evidence for increased age at …

Chronic Kidney Disease Promotes Atrial Fibrillation Via Inflammasome Pathway Activation, Jia Song, Jose Alberto Navarro-Garcia, Jiao Wu, Arnela Saljic, Issam Abu-Taha, Luge Li, Satadru K Lahiri, Joshua A Keefe, Yuriana Aguilar-Sanchez, Oliver M Moore, Yue Yuan, Xiaolei Wang, Markus Kamler, William E Mitch, Gema Ruiz-Hurtado, Zhaoyong Hu, Sandhya S Thomas, Dobromir Dobrev, Xander Ht Wehrens, Na Li

Faculty, Staff and Students Publications

Chronic kidney disease (CKD) is associated with a higher risk of atrial fibrillation (AF). The mechanistic link between CKD and AF remains elusive. IL-1β, a main effector of NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, is a key modulator of conditions associated with inflammation, such as AF and CKD. Circulating IL-1β levels were elevated in patients with CKD who had AF (versus patients with CKD in sinus rhythm). Moreover, NLRP3 activity was enhanced in atria of patients with CKD. To elucidate the role of NLRP3/IL-1β signaling in the pathogenesis of CKD-induced AF, Nlrp3-/- and WT mice were subjected to …

Kinome Reprogramming Is A Targetable Vulnerability In Esr1 Fusion-Driven Breast Cancer, Xuxu Gou, Beom-Jun Kim, Meenakshi Anurag, Jonathan T Lei, Meggie N Young, Matthew V Holt, Diana Fandino, Craig T Vollert, Purba Singh, Mohammad A Alzubi, Anna Malovannaya, Lacey E Dobrolecki, Michael T Lewis, Shunqiang Li, Charles E Foulds, Matthew J Ellis

Faculty, Staff and Students Publications

Transcriptionally active ESR1 fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs are not directly druggable because the C-terminal estrogen/anti-estrogen-binding domain is replaced with translocated in-frame partner gene sequences that confer constitutive transactivation. To discover alternative treatments, a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) was deployed to identify druggable kinases that are upregulated by diverse ESR1-TAFs. Subsequent explorations of drug sensitivity validated RET kinase as a common therapeutic vulnerability despite remarkable ESR1-TAF C-terminal sequence and structural diversity. Organoids and xenografts from a pan-ET-resistant patient-derived xenograft model that harbors the ESR1-e6>YAP1 TAF were …

Availability Of Family Caregiver Programs In Us Cancer Centers, J Nicholas Odom, Allison Applebaum, Marie A Bakitas, Tara Bryant, Erin Currie, Kayleigh Curry, Heidi Donovan, Maria E Fernandez, Betty Ferrell, Andres Azuero, Tamryn F Gray, Bailey A Hendricks, Diane Meier, Chandylen Nightingale, Susan Reinhard, Timothy S Sannes, Katherine Sterba, Heather M Young

Faculty, Staff and Student Publications

Importance: Family caregivers provide the majority of health care to the 18 million patients with cancer in the US. Yet despite providing complex medical and nursing care, a large proportion of caregivers report no formal support or training. In recognition of this gap, many interventions to support cancer caregivers have been developed and tested over the past 2 decades. However, there are few system-level data on whether US cancer centers have adopted and implemented these interventions.

Objective: To describe and characterize the availability of family caregiver support programs in US cancer centers.

Design, setting, and participants: This cross-sectional national survey …

Association Of Parental Status And Gender With Burden Of Multidisciplinary Tumor Boards Among Oncology Physicians, Brittney L Chau, Jonnby S Laguardia, Sungjin Kim, Samuel C Zhang, Eric Pletcher, Nina N Sanford, Ann C Raldow, Lisa Singer, Jun Gong, Sukhmani K Padda, Mitchell Kamrava, Tara Cohen, Devarati Mitra, Katelyn M Atkins

Faculty, Staff and Student Publications

IMPORTANCE: Tumor boards are integral to the care of patients with cancer. However, data investigating the burden of tumor boards on physicians are limited.

OBJECTIVE: To investigate what physician-related and tumor board-related factors are associated with higher tumor board burden among oncology physicians.

DESIGN, SETTING, AND PARTICIPANTS: Tumor board burden was assessed by a cross-sectional convenience survey posted on social media and by email to Cedars-Sinai Medical Center cancer physicians between March 3 and April 3, 2022. Tumor board start times were independently collected by email from 22 top cancer centers.

MAIN OUTCOMES AND MEASURES: Tumor board burden was measured …

Accuracy And Reliability Of Chatbot Responses To Physician Questions, Rachel S Goodman, Isik Turker, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Natural language processing tools, such as ChatGPT (generative pretrained transformer, hereafter referred to as chatbot), have the potential to radically enhance the accessibility of medical information for health professionals and patients. Assessing the safety and efficacy of these tools in answering physician-generated questions is critical to determining their suitability in clinical settings, facilitating complex decision-making, and optimizing health care efficiency.

OBJECTIVE: To assess the accuracy and comprehensiveness of chatbot-generated responses to physician-developed medical queries, highlighting the reliability and limitations of artificial intelligence-generated medical information.

DESIGN, SETTING, AND PARTICIPANTS: Thirty-three physicians across 17 specialties generated 284 medical questions that they …

Setd2 Loss And Atr Inhibition Synergize To Promote Cgas Signaling And Immunotherapy Response In Renal Cell Carcinoma, Xian-De Liu, Yan-Ting Zhang, Daniel J Mcgrail, Xuesong Zhang, Truong Lam, Anh Hoang, Elshad Hasanov, Ganiraju Manyam, Christine B Peterson, Haifeng Zhu, Shwetha V Kumar, Rehan Akbani, Patrick G Pilie, Nizar M Tannir, Guang Peng, Eric Jonasch

Faculty, Staff and Student Publications

PURPOSE: Immune checkpoint blockade (ICB) demonstrates durable clinical benefits in a minority of patients with renal cell carcinoma (RCC). We aimed to identify the molecular features that determine the response and develop approaches to enhance it.

EXPERIMENTAL DESIGN: We investigated the effects of SET domain-containing protein 2 (SETD2) loss on the DNA damage response pathway, the cytosolic DNA-sensing pathway, the tumor immune microenvironment, and the response to ataxia telangiectasia and rad3-related (ATR) and checkpoint inhibition in RCC.

RESULTS: ATR inhibition activated the cyclic GMP-AMP synthase (cGAS)-interferon regulatory factor 3 (IRF3)-dependent cytosolic DNA-sensing pathway, resulting in the concurrent expression of inflammatory …

Safety And Tolerability Of A Novel Anti-Her2 Antibody-Drug Conjugate (Pf-06804103) In Patients With Her2-Expressing Solid Tumors: A Phase 1 Dose-Escalation Study, Funda Meric-Bernstam, Emiliano Calvo, Keun Seok Lee, Victor Moreno, Yeon Hee Park, Sun Young Rha, Pavani Chalasani, Wei Zhong, Li Zhou, Steven Pirie-Shepherd, Abraham C F Leung, Giuseppe Curigliano

Faculty, Staff and Student Publications

PF-06804103 is an anti-HER2 antibody–drug conjugate with auristatin payload. We evaluated its safety, tolerability, and antitumor activity in patients with advanced/unresectable or metastatic breast and gastric cancers. This multicenter, open-label, first-in-human, phase 1 study (NCT03284723) comprised dose escalation (P1) and dose expansion (P2). In P1, adults with HER2+ breast or gastric cancer received PF-06804103 0.15–5.0 mg/kg intravenously once/21 days (Q3W); in P2, patients with HER2+ or HER2-low (IHC 1+ or IHC 2+/ISH−) breast cancer received 3.0 or 4.0 mg/kg Q3W. The primary endpoints were dose-limiting toxicities (DLT) and safety (P1), and objective response rate (ORR) assessed using RECIST v1.1 (P2). …

Intraperitoneal Paclitaxel Is A Safe And Effective Therapeutic Strategy For Treating Mucinous Appendiceal Adenocarcinoma, Ichiaki Ito, Abdelrahman M G Yousef, Saikat Chowdhury, Princess N Dickson, Zahra A Naini, Michael G White, Karianne G Fleten, Kjersti Flatmark, Keith F Fournier, Natalie W Fowlkes, John Paul Shen

Faculty, Staff and Student Publications

Appendiceal adenocarcinomas (AAs) are a rare and heterogeneous mix of tumors for which few preclinical models exist. The rarity of AA has made performing prospective clinical trials difficult, which has partly contributed to AA remaining an orphan disease with no chemotherapeutic agents approved by the FDA for its treatment. AA has a unique biology in which it frequently forms diffuse peritoneal metastases but almost never spreads via a hematogenous route and rarely spreads to lymphatics. Given the localization of AA to the peritoneal space, intraperitoneal (IP) delivery of chemotherapy could be an effective treatment strategy. Here, we tested the efficacy …

Deep Learning For Fully Automatic Tumor Segmentation On Serially Acquired Dynamic Contrast-Enhanced Mri Images Of Triple-Negative Breast Cancer, Zhan Xu, David E Rauch, Rania M Mohamed, Sanaz Pashapoor, Zijian Zhou, Bikash Panthi, Jong Bum Son, Ken-Pin Hwang, Benjamin C Musall, Beatriz E Adrada, Rosalind P Candelaria, Jessica W T Leung, Huong T C Le-Petross, Deanna L Lane, Frances Perez, Jason White, Alyson Clayborn, Brandy Reed, Huiqin Chen, Jia Sun, Peng Wei, Alastair Thompson, Anil Korkut, Lei Huo, Kelly K Hunt, Jennifer K Litton, Vicente Valero, Debu Tripathy, Wei Yang, Clinton Yam, Jingfei Ma

Faculty, Staff and Student Publications

Accurate tumor segmentation is required for quantitative image analyses, which are increasingly used for evaluation of tumors. We developed a fully automated and high-performance segmentation model of triple-negative breast cancer using a self-configurable deep learning framework and a large set of dynamic contrast-enhanced MRI images acquired serially over the patients' treatment course. Among all models, the top-performing one that was trained with the images across different time points of a treatment course yielded a Dice similarity coefficient of 93% and a sensitivity of 96% on baseline images. The top-performing model also produced accurate tumor size measurements, which is valuable for …

Endocrine Therapy Synergizes With Smac Mimetics To Potentiate Antigen Presentation And Tumor Regression In Hormone Receptor-Positive Breast Cancer, Francisco Hermida-Prado, Yingtian Xie, Shira Sherman, Zsuzsanna Nagy, Douglas Russo, Tara Akhshi, Zhengtao Chu, Avery Feit, Marco Campisi, Minyue Chen, Agostina Nardone, Cristina Guarducci, Klothilda Lim, Alba Font-Tello, Irene Lee, Juana García-Pedrero, Israel Cañadas, Judith Agudo, Ying Huang, Tal Sella, Qingchun Jin, Nabihah Tayob, Elizabeth A Mittendorf, Sara M Tolaney, Xintao Qiu, Henry Long, William F Symmans, Jia-Ren Lin, Sandro Santagata, Isabelle Bedrosian, Denise A Yardley, Ingrid A Mayer, Edward T Richardson, Giacomo Oliveira, Catherine J Wu, Eugene F Schuster, Mitch Dowsett, Alana L Welm, David Barbie, Otto Metzger, Rinath Jeselsohn

Faculty, Staff and Student Publications

Immunotherapies have yet to demonstrate significant efficacy in the treatment of hormone receptor-positive (HR+) breast cancer. Given that endocrine therapy (ET) is the primary approach for treating HR+ breast cancer, we investigated the effects of ET on the tumor immune microenvironment (TME) in HR+ breast cancer. Spatial proteomics of primary HR+ breast cancer samples obtained at baseline and after ET from patients enrolled in a neoadjuvant clinical trial (NCT02764541) indicated that ET upregulated β2-microglobulin and influenced the TME in a manner that promotes enhanced immunogenicity. To gain a deeper understanding of the underlying mechanisms, the intrinsic effects of …