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Full-Text Articles in Medicine and Health Sciences

High-Fat Diet, But Not Duration Of Lactation, Increases Mammary Gland Lymphatic Vessel Function And Subsequent Growth Of Inflammatory Breast Cancer Cells, Wintana Balema, Janelle Morton, Richard A Larson, Li Li, Fred Christian Velasquez, Natalie W Fowlkes, Savitri Krishnamurthy, Bisrat G Debeb, Eva Sevick-Muraca, Wendy A Woodward Oct 2023

High-Fat Diet, But Not Duration Of Lactation, Increases Mammary Gland Lymphatic Vessel Function And Subsequent Growth Of Inflammatory Breast Cancer Cells, Wintana Balema, Janelle Morton, Richard A Larson, Li Li, Fred Christian Velasquez, Natalie W Fowlkes, Savitri Krishnamurthy, Bisrat G Debeb, Eva Sevick-Muraca, Wendy A Woodward

Faculty, Staff and Student Publications

Inflammatory breast cancer (IBC) presents as rapid-onset swelling and breast skin changes caused by tumor emboli in the breast and breast skin lymphatics. IBC has been linked with obesity and duration of breastfeeding, but how these factors affect IBC tumor progression is not clear. We modeled the simultaneous effects of diet and weaning in mice on in vivo lymphatic function; on IBC tumor growth; and on aspects of the mammary gland microenvironment before and after IBC (SUM149) xenograft inoculation. We hypothesized that weaning status and diet would have synergistic effects on lymphatic function and the breast microenvironment to enhance IBC …


Epigenomic Signature Of Major Congenital Heart Defects In Newborns With Down Syndrome, Julia S Mouat, Shaobo Li, Swe Swe Myint, Benjamin I Laufer, Philip J Lupo, Jeremy M Schraw, John P Woodhouse, Adam J De Smith, Janine M Lasalle Oct 2023

Epigenomic Signature Of Major Congenital Heart Defects In Newborns With Down Syndrome, Julia S Mouat, Shaobo Li, Swe Swe Myint, Benjamin I Laufer, Philip J Lupo, Jeremy M Schraw, John P Woodhouse, Adam J De Smith, Janine M Lasalle

Faculty, Staff and Students Publications

BACKGROUND: Congenital heart defects (CHDs) affect approximately half of individuals with Down syndrome (DS), but the molecular reasons for incomplete penetrance are unknown. Previous studies have largely focused on identifying genetic risk factors associated with CHDs in individuals with DS, but comprehensive studies of the contribution of epigenetic marks are lacking. We aimed to identify and characterize DNA methylation differences from newborn dried blood spots (NDBS) of DS individuals with major CHDs compared to DS individuals without CHDs.

METHODS: We used the Illumina EPIC array and whole-genome bisulfite sequencing (WGBS) to quantitate DNA methylation for 86 NDBS samples from the …


Greater Number Of Weekly Stairs Climbed Is Associated With Lower Low Back Pain Prevalence Among Female But Not Male Physical Therapists, Amy H. Amabile, Sharon L. Larson, Lisa T. Hoglund, John P. Guarnieri, Maureen Mcdonald, Madeline R. Reich Oct 2023

Greater Number Of Weekly Stairs Climbed Is Associated With Lower Low Back Pain Prevalence Among Female But Not Male Physical Therapists, Amy H. Amabile, Sharon L. Larson, Lisa T. Hoglund, John P. Guarnieri, Maureen Mcdonald, Madeline R. Reich

Department of Physical Therapy Faculty Papers

INTRODUCTION: Certain cardiovascular health benefits of stair climbing are now widely accepted, but no prior studies have as yet been found linking the quantity of stairs climbed to low back pain (LBP) morbidity. Low back pain is a common musculoskeletal impairment, and research has begun to show an association between LBP and gluteus maximus (GM) weakness. With stair climbing being the activity which most activates GM, the aim of the present research was to assess the relationship between stair ambulation and LBP prevalence. The hypothesis of this cross-sectional study was that individuals with LBP would report a significantly lower numbers …


Greater Number Of Weekly Stairs Climbed Is Associated With Lower Low Back Pain Prevalence Among Female But Not Male Physical Therapists, Amy H. Amabile, Sharon L. Larson, Lisa T. Hoglund, John P. Guarnieri, Maureen Mcdonald, Madeline R. Reich Oct 2023

Greater Number Of Weekly Stairs Climbed Is Associated With Lower Low Back Pain Prevalence Among Female But Not Male Physical Therapists, Amy H. Amabile, Sharon L. Larson, Lisa T. Hoglund, John P. Guarnieri, Maureen Mcdonald, Madeline R. Reich

Department of Physical Therapy Faculty Papers

INTRODUCTION: Certain cardiovascular health benefits of stair climbing are now widely accepted, but no prior studies have as yet been found linking the quantity of stairs climbed to low back pain (LBP) morbidity. Low back pain is a common musculoskeletal impairment, and research has begun to show an association between LBP and gluteus maximus (GM) weakness. With stair climbing being the activity which most activates GM, the aim of the present research was to assess the relationship between stair ambulation and LBP prevalence. The hypothesis of this cross-sectional study was that individuals with LBP would report a significantly lower numbers …


Müllerian-Type Clear Cell Carcinoma Of Donor Origin In A Male Patient With A Kidney Transplant: Ascertained By Molecular Testing, J Bryan Iorgulescu, Leah K Shaw, Asif Rashid, Priya Rao, Sreedhar Mandayam, Keyur P Patel, Kathleen M Schmeler, Richard K Yang, Pavlos Msaouel Oct 2023

Müllerian-Type Clear Cell Carcinoma Of Donor Origin In A Male Patient With A Kidney Transplant: Ascertained By Molecular Testing, J Bryan Iorgulescu, Leah K Shaw, Asif Rashid, Priya Rao, Sreedhar Mandayam, Keyur P Patel, Kathleen M Schmeler, Richard K Yang, Pavlos Msaouel

Faculty, Staff and Student Publications

Clear cell carcinomas of Müllerian origin have a strong female predominance and only extremely rarely will arise within the kidney, presumably due to ectopic Müllerian embryogenesis. Herein, we report a unique case of metastatic Müllerian type clear cell carcinoma in a 37-year-old patient who had previously received a transplanted kidney from his father at age 11 (due to severe bilateral vesicoureteral reflux) and remained on chronic immunosuppression. The tumor was highly aggressive and demonstrated somatic mutations in NF2 and SETD2. Imaging of the transplanted kidney did not reveal any clear evidence of malignancy. However, targeted multigene sequencing and short tandem …


In-Utero Exposure To Antibiotics And Risk Of Colorectal Cancer In A Prospective Cohort Of 18 000 Adult Offspring, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Amit G Singal, Dean P Jones, Timothy Zaki, Barbara A Cohn Oct 2023

In-Utero Exposure To Antibiotics And Risk Of Colorectal Cancer In A Prospective Cohort Of 18 000 Adult Offspring, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Amit G Singal, Dean P Jones, Timothy Zaki, Barbara A Cohn

Faculty, Staff and Student Publications

BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among younger adults and in mid-life, implicating exposures in early life as risk factors. We examined the association between in-utero exposure to antibiotics and risk of CRC in adult offspring.

METHODS: The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California, with deliveries through June 1967. Diagnosed conditions and all prescribed medications were abstracted from mothers' medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received antibiotics in pregnancy, including penicillins, tetracyclines, short-acting sulfonamides …


Global Effect Of Modifiable Risk Factors On Cardiovascular Disease And Mortality, Global Cardiovascular Risk Consortium, Christina Magnussen, Francisco M Ojeda, Darryl P Leong, Jesus Alegre-Diaz, Philippe Amouyel, Larissa Aviles-Santa, Dirk De Bacquer, Christie M Ballantyne, Antonio Bernabé-Ortiz, Martin Bobak, Hermann Brenner, Rodrigo M Carrillo-Larco, James De Lemos, Annette Dobson, Marcus Dörr, Chiara Donfrancesco, Wojciech Drygas, Robin P Dullaart, Gunnar Engström, Marco M Ferrario, Jean Ferrières, Giovanni De Gaetano, Uri Goldbourt, Clicerio Gonzalez, Guido Grassi, Allison M Hodge, Kristian Hveem, Licia Iacoviello, M Kamran Ikram, Vilma Irazola, Modou Jobe, Pekka Jousilahti, Pontiano Kaleebu, Maryam Kavousi, Frank Kee, Davood Khalili, Wolfgang Koenig, Anna Kontsevaya, Kari Kuulasmaa, Karl J Lackner, David M Leistner, Lars Lind, Allan Linneberg, Thiess Lorenz, Magnus Nakrem Lyngbakken, Reza Malekzadeh, Sofia Malyutina, Ellisiv B Mathiesen, Olle Melander, Andres Metspalu, J Jaime Miranda, Marie Moitry, Joseph Mugisha, Mahdi Nalini, Vijay Nambi, Toshiharu Ninomiya, Karen Oppermann, Eleonora D'Orsi, Andrzej Pająk, Luigi Palmieri, Demosthenes Panagiotakos, Arokiasamy Perianayagam, Annette Peters, Hossein Poustchi, Andrew M Prentice, Eva Prescott, Ulf Risérus, Veikko Salomaa, Susana Sans, Satoko Sakata, Ben Schöttker, Aletta E Schutte, Sadaf G Sepanlou, Sanjib Kumar Sharma, Jonathan E Shaw, Leon A Simons, Stefan Söderberg, Abdonas Tamosiunas, Barbara Thorand, Hugh Tunstall-Pedoe, Raphael Twerenbold, Diego Vanuzzo, Giovanni Veronesi, Julia Waibel, S Goya Wannamethee, Masafumi Watanabe, Philipp S Wild, Yao Yao, Yi Zeng, Andreas Ziegler, Stefan Blankenberg Oct 2023

Global Effect Of Modifiable Risk Factors On Cardiovascular Disease And Mortality, Global Cardiovascular Risk Consortium, Christina Magnussen, Francisco M Ojeda, Darryl P Leong, Jesus Alegre-Diaz, Philippe Amouyel, Larissa Aviles-Santa, Dirk De Bacquer, Christie M Ballantyne, Antonio Bernabé-Ortiz, Martin Bobak, Hermann Brenner, Rodrigo M Carrillo-Larco, James De Lemos, Annette Dobson, Marcus Dörr, Chiara Donfrancesco, Wojciech Drygas, Robin P Dullaart, Gunnar Engström, Marco M Ferrario, Jean Ferrières, Giovanni De Gaetano, Uri Goldbourt, Clicerio Gonzalez, Guido Grassi, Allison M Hodge, Kristian Hveem, Licia Iacoviello, M Kamran Ikram, Vilma Irazola, Modou Jobe, Pekka Jousilahti, Pontiano Kaleebu, Maryam Kavousi, Frank Kee, Davood Khalili, Wolfgang Koenig, Anna Kontsevaya, Kari Kuulasmaa, Karl J Lackner, David M Leistner, Lars Lind, Allan Linneberg, Thiess Lorenz, Magnus Nakrem Lyngbakken, Reza Malekzadeh, Sofia Malyutina, Ellisiv B Mathiesen, Olle Melander, Andres Metspalu, J Jaime Miranda, Marie Moitry, Joseph Mugisha, Mahdi Nalini, Vijay Nambi, Toshiharu Ninomiya, Karen Oppermann, Eleonora D'Orsi, Andrzej Pająk, Luigi Palmieri, Demosthenes Panagiotakos, Arokiasamy Perianayagam, Annette Peters, Hossein Poustchi, Andrew M Prentice, Eva Prescott, Ulf Risérus, Veikko Salomaa, Susana Sans, Satoko Sakata, Ben Schöttker, Aletta E Schutte, Sadaf G Sepanlou, Sanjib Kumar Sharma, Jonathan E Shaw, Leon A Simons, Stefan Söderberg, Abdonas Tamosiunas, Barbara Thorand, Hugh Tunstall-Pedoe, Raphael Twerenbold, Diego Vanuzzo, Giovanni Veronesi, Julia Waibel, S Goya Wannamethee, Masafumi Watanabe, Philipp S Wild, Yao Yao, Yi Zeng, Andreas Ziegler, Stefan Blankenberg

Faculty, Staff and Students Publications

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease (CVD) and all-cause mortality. The regional and sex-specific prevalence of these modifiable risk factors and their impact on CVD and all-cause mortality have not been evaluated using individual-level data.

METHODS: The Global Cardiovascular Risk Consortium harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions. Associations between body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, smoking, and diabetes with incident CVD and all-cause mortality were examined using Cox regression analyses and stratified by geographic region, age and sex. Population-attributable fractions were estimated for 10-year incident …


Multivariate Gwas Of Alzheimer's Disease Csf Biomarker Profiles Implies Grin2d In Synaptic Functioning, Alexander Neumann, Jigyasha Timsina, Thomas W Marsh, Priyanka Gorijala, Carlos Cruchaga, Et Al. Oct 2023

Multivariate Gwas Of Alzheimer's Disease Csf Biomarker Profiles Implies Grin2d In Synaptic Functioning, Alexander Neumann, Jigyasha Timsina, Thomas W Marsh, Priyanka Gorijala, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

BACKGROUND: Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.

METHODS: We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD …


Association Between Socioeconomic Factors, Race, And Use Of A Specialty Memory Clinic, Abigail Lewis, Aditi Gupta, Inez Oh, Suzanne E. Schindler, Nupur Ghoshal, Zachary Abrams, Randi Foraker, Barbara Joy Snider, John C. Morris, Joyce Balls-Berry, Mahendra Gupta, Philip R. O. Payne, Albert M. Lai Oct 2023

Association Between Socioeconomic Factors, Race, And Use Of A Specialty Memory Clinic, Abigail Lewis, Aditi Gupta, Inez Oh, Suzanne E. Schindler, Nupur Ghoshal, Zachary Abrams, Randi Foraker, Barbara Joy Snider, John C. Morris, Joyce Balls-Berry, Mahendra Gupta, Philip R. O. Payne, Albert M. Lai

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: The capacity of specialty memory clinics in the United States is very limited. If lower socioeconomic status or minoritized racial group is associated with reduced use of memory clinics, this could exacerbate health care disparities, especially if more effective treatments of Alzheimer disease become available. We aimed to understand how use of a memory clinic is associated with neighborhood-level measures of socioeconomic factors and the intersectionality of race.

METHODS: We conducted an observational cross-sectional study using electronic health record data to compare the neighborhood advantage of patients seen at the Washington University Memory Diagnostic Center with the …


Quality Of Life In Male Breast Cancer: Prospective Study Of The International Male Breast Cancer Program (Eortc10085/Tbcrc029/Big2-07/Nabcg), Carolien P Schröder, Elise Van Leeuwen-Stok, Fatima Cardoso, Barbro Linderholm, Coralie Poncet, Antonio C Wolff, Vesna Bjelic-Radisic, Gustavo Werutsky, Miguel H Abreu, Ivana Bozovic-Spasojevic, Irma Den Hoed, Aafke H Honkoop, Maartje Los, Jose P Leone, Nicola S Russell, Tineke J Smilde, Annette W G Van Der Velden, Catherine Van Poznak, Marije M Vleugel, Rachel L Yung, Corneel Coens, Sharon H Giordano, Kathryn J Ruddy Oct 2023

Quality Of Life In Male Breast Cancer: Prospective Study Of The International Male Breast Cancer Program (Eortc10085/Tbcrc029/Big2-07/Nabcg), Carolien P Schröder, Elise Van Leeuwen-Stok, Fatima Cardoso, Barbro Linderholm, Coralie Poncet, Antonio C Wolff, Vesna Bjelic-Radisic, Gustavo Werutsky, Miguel H Abreu, Ivana Bozovic-Spasojevic, Irma Den Hoed, Aafke H Honkoop, Maartje Los, Jose P Leone, Nicola S Russell, Tineke J Smilde, Annette W G Van Der Velden, Catherine Van Poznak, Marije M Vleugel, Rachel L Yung, Corneel Coens, Sharon H Giordano, Kathryn J Ruddy

Faculty, Staff and Student Publications

INTRODUCTION: Prospective data about quality of life (QoL) in men with breast cancer (BC) are lacking. A prospective registry (EORTC10085) of men with all BC stages, including a QoL correlative study, was performed as part of the International Male Breast Cancer Program.

METHODS: Questionnaires at BC diagnosis included the EORTC QLQ-C30 and BR23 (BC specific module), adapted for men. High functioning and global health/QoL scores indicate high functioning levels/high QoL; high symptom-focused measures scores indicate high symptoms/problems levels. EORTC reference data for healthy men and women with BC were used for comparisons.

RESULTS: Of 422 men consenting to participate, 363 …


The Breast Cancer Proteome And Precision Oncology, Jonathan T Lei, Eric J Jaehnig, Hannah Smith, Matthew V Holt, Xi Li, Meenakshi Anurag, Matthew J Ellis, Gordon B Mills, Bing Zhang, Marilyne Labrie Oct 2023

The Breast Cancer Proteome And Precision Oncology, Jonathan T Lei, Eric J Jaehnig, Hannah Smith, Matthew V Holt, Xi Li, Meenakshi Anurag, Matthew J Ellis, Gordon B Mills, Bing Zhang, Marilyne Labrie

Faculty, Staff and Students Publications

The goal of precision oncology is to translate the molecular features of cancer into predictive and prognostic tests that can be used to individualize treatment leading to improved outcomes and decreased toxicity. Success for this strategy in breast cancer is exemplified by efficacy of trastuzumab in tumors overexpressing ERBB2 and endocrine therapy for tumors that are estrogen receptor positive. However, other effective treatments, including chemotherapy, immune checkpoint inhibitors, and CDK4/6 inhibitors are not associated with strong predictive biomarkers. Proteomics promises another tier of information that, when added to genomic and transcriptomic features (proteogenomics), may create new opportunities to improve both …


Vertebral Tortuosity Is Associated With Increased Rate Of Cardiovascular Events In Vascular Ehlers-Danlos Syndrome, Sara B Stephens, Sherene Shalhub, Nicholas Dodd, Jesse Li, Michael Huang, Seitaro Oda, Kalyan Kancherla, Tam T Doan, Siddharth K Prakash, Justin D Weigand, Federico M Asch, Taylor Beecroft, Alana Cecchi, Teniola Shittu, Liliana Preiss, Scott A Lemaire, Richard B Devereux, Reed E Pyeritz, Kathryn W Holmes, Mary J Roman, Ronald V Lacro, Ralph V Shohet, Rajesh Krishnamurthy, Kim Eagle, Peter Byers, Dianna M Milewicz, Shaine A Morris Oct 2023

Vertebral Tortuosity Is Associated With Increased Rate Of Cardiovascular Events In Vascular Ehlers-Danlos Syndrome, Sara B Stephens, Sherene Shalhub, Nicholas Dodd, Jesse Li, Michael Huang, Seitaro Oda, Kalyan Kancherla, Tam T Doan, Siddharth K Prakash, Justin D Weigand, Federico M Asch, Taylor Beecroft, Alana Cecchi, Teniola Shittu, Liliana Preiss, Scott A Lemaire, Richard B Devereux, Reed E Pyeritz, Kathryn W Holmes, Mary J Roman, Ronald V Lacro, Ralph V Shohet, Rajesh Krishnamurthy, Kim Eagle, Peter Byers, Dianna M Milewicz, Shaine A Morris

Faculty, Staff and Student Publications

Background Arterial tortuosity is associated with adverse events in Marfan and Loeys-Dietz syndromes but remains understudied in Vascular Ehlers-Danlos syndrome. Methods and Results Subjects with a pathogenic


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 Oct 2023

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 …


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 Oct 2023

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 …


Abemaciclib Is Effective In Palbociclib-Resistant Hormone Receptor-Positive Metastatic Breast Cancers, Juliana Navarro-Yepes, Nicole M Kettner, Xiayu Rao, Cassandra Santaella Bishop, Tuyen N Bui, Hannah F Wingate, Akshara Singareeka Raghavendra, Yan Wang, Jing Wang, Aysegul A Sahin, Funda Meric-Bernstam, Kelly K Hunt, Senthil Damodaran, Debu Tripathy, Khandan Keyomarsi Oct 2023

Abemaciclib Is Effective In Palbociclib-Resistant Hormone Receptor-Positive Metastatic Breast Cancers, Juliana Navarro-Yepes, Nicole M Kettner, Xiayu Rao, Cassandra Santaella Bishop, Tuyen N Bui, Hannah F Wingate, Akshara Singareeka Raghavendra, Yan Wang, Jing Wang, Aysegul A Sahin, Funda Meric-Bernstam, Kelly K Hunt, Senthil Damodaran, Debu Tripathy, Khandan Keyomarsi

Faculty, Staff and Student Publications

Cyclin-dependent kinases 4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) is standard of care for patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). However, resistance to CDK4/6is plus ET remains a clinical problem with limited therapeutic options following disease progression. Different CDK4/6is might have distinct mechanisms of resistance, and therefore using them sequentially or targeting their differentially altered pathways could delay disease progression. To understand pathways leading to resistance to the CDK4/6is palbociclib and abemaciclib, we generated multiple in vitro models of palbociclib-resistant (PR) and abemaciclib-resistant (AR) cell lines as well as in vivo patient-derived xenografts (PDX) and ex …


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 Oct 2023

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 …


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 Oct 2023

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). …


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 Oct 2023

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 …


Interplay Between Esr1/Pik3ca Codon Variants, Oncogenic Pathway Alterations And Clinical Phenotype In Patients With Metastatic Breast Cancer (Mbc): Comprehensive Circulating Tumor Dna (Ctdna) Analysis, Lorenzo Gerratana, Andrew A Davis, Katherine Clifton, Whitney L Hensing, Cynthia X Ma, Et Al. Oct 2023

Interplay Between Esr1/Pik3ca Codon Variants, Oncogenic Pathway Alterations And Clinical Phenotype In Patients With Metastatic Breast Cancer (Mbc): Comprehensive Circulating Tumor Dna (Ctdna) Analysis, Lorenzo Gerratana, Andrew A Davis, Katherine Clifton, Whitney L Hensing, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

BACKGROUND: although being central for the biology and druggability of hormone-receptor positive, HER2 negative metastatic breast cancer (MBC), ESR1 and PIK3CA mutations are simplistically dichotomized as mutated or wild type in current clinical practice.

METHODS: The study analyzed a multi-institutional cohort comprising 703 patients with luminal-like MBC characterized for circulating tumor DNA through next generation sequencing (NGS). Pathway classification was defined based on previous work (i.e., RTK, RAS, RAF, MEK, NRF2, ER, WNT, MYC, P53, cell cycle, notch, PI3K). Single nucleotide variations (SNVs) were annotated for their oncogenicity through OncoKB. Only pathogenic variants were included in the models. Associations among …


Kinome Reprogramming Is A Targetable Vulnerability In Esr1 Fusion-Driven Breast Cancer, Xuxu Gou, Shunqiang Li, Et Al. Oct 2023

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 …


Pretibial Myxedema: An Unusual Presentation, Dāsha Giger, Christina E. Borchers, Samia Borchers Oct 2023

Pretibial Myxedema: An Unusual Presentation, Dāsha Giger, Christina E. Borchers, Samia Borchers

Dermatology Faculty Publications

Pretibial myxedema presents with indurated nodules or plaques that can be erythematous or vary in color from purple-brown to yellow. It is noted that a peau d’orange appearanceis a characteristic finding. These lesions are typically located on the anterolateral aspect of the lower legs. Non-pitting edema of the shins that evolves into elephantiasis is anotherpotential presentation seen in pretibial myxedema. It is often associated with hyperthyroidism, particularly Graves disease and is more commonly seen in women than men.Typically, it presents during the third or fourth decade of life. Differential diagnoses include but are not limited to stasis dermatitis, hypertrophic lichen …


Does Spasticity Correlate With Motor Impairment In The Upper And Lower Limbs In Ambulatory Chronic Stroke Survivors??, Sheng Li, Jaskiran Ghuman, Javier Gonzalez-Buonomo, Xinran Huang, Aila Malik, Nuray Yozbatiran, Gerard E Francisco, Hulin Wu, Walter R Frontera Oct 2023

Does Spasticity Correlate With Motor Impairment In The Upper And Lower Limbs In Ambulatory Chronic Stroke Survivors??, Sheng Li, Jaskiran Ghuman, Javier Gonzalez-Buonomo, Xinran Huang, Aila Malik, Nuray Yozbatiran, Gerard E Francisco, Hulin Wu, Walter R Frontera

Faculty, Staff and Student Publications

OBJECTIVE: This study aimed to explore correlations between spasticity and motor impairments in the upper and lower limbs in ambulatory chronic stroke survivors.

DESIGN: We performed clinical assessments in 28 ambulatory chronic stroke survivors with spastic hemiplegia (female: 12; male: 16; mean ages = 57.8 ± 11.8 yrs; 76 ± 45 mos after stroke).

RESULTS: In the upper limb, spasticity index and Fugl-Meyer Motor Assessment showed a significant correlation. Spasticity index for the upper limb showed a significant negative correlation with handgrip strength of the affected side ( r = -0.4, P = 0.035) while Fugl-Meyer Motor Assessment for the …


Multilevel Community Engagement To Inform A Randomized Clinical Trial, Kirby L. Wycoff, Jabina G. Coleman, Christine M. Santoro, Leah L. Zullig, Niesha Darden, Porsche M. Holland, Jane F. Cruice, Shukriyyah Mitchell, Michelle Smith, Saleemah J. Mcneil, Sharon J. Herring Oct 2023

Multilevel Community Engagement To Inform A Randomized Clinical Trial, Kirby L. Wycoff, Jabina G. Coleman, Christine M. Santoro, Leah L. Zullig, Niesha Darden, Porsche M. Holland, Jane F. Cruice, Shukriyyah Mitchell, Michelle Smith, Saleemah J. Mcneil, Sharon J. Herring

Counseling and Behavioral Health Faculty Papers

OBJECTIVE: To explore how patients, community-based perinatal support professionals, and health system clinicians and staff perceived facilitators and barriers to implementation of a randomized clinical trial (RCT) designed to optimize Black maternal heart health.

METHODS: This article describes the formative work that we believed needed to occur before the start of the Change of H.E.A.R.T (Here for Equity, Advocacy, Reflection and Transformation) RCT. We used a qualitative, descriptive design and community-based, participatory approach, the latter of which allowed our team to intentionally focus on avoiding harm and equalizing power dynamics throughout the research process. Data were collected between November 2021 …


“But My Mom Still Blinks When I Talk To Her” Understanding The Concept Of Social Death To Avoid Bias And Improve Goals-Of-Care Discussions At The End Of Life, Joelle Robertson-Preidler, Holland Kaplan Oct 2023

“But My Mom Still Blinks When I Talk To Her” Understanding The Concept Of Social Death To Avoid Bias And Improve Goals-Of-Care Discussions At The End Of Life, Joelle Robertson-Preidler, Holland Kaplan

Faculty and Staff Publications

No abstract provided.


A Blood Biomarker Test For Brain Amyloid Impacts The Clinical Evaluation Of Cognitive Impairment, Mark Monane, B Joy Snider, Et Al. Oct 2023

A Blood Biomarker Test For Brain Amyloid Impacts The Clinical Evaluation Of Cognitive Impairment, Mark Monane, B Joy Snider, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The objective of this study was to examine clinicians' patient selection and result interpretation of a clinically validated mass spectrometry test measuring amyloid beta and ApoE blood biomarkers combined with patient age (PrecivityAD® blood test) in symptomatic patients evaluated for Alzheimer's disease (AD) or other causes of cognitive decline.

METHODS: The Quality Improvement and Clinical Utility PrecivityAD Clinician Survey (QUIP I, ClinicalTrials.gov Identifier: NCT05477056) was a prospective, single-arm cohort study among 366 patients evaluated by neurologists and other cognitive specialists. Participants underwent blood biomarker testing and received an amyloid probability score (APS), indicating the likelihood of a positive result …


Racial And Ethnic Disparities In Cervical Cancer Screening From Three U.S. Healthcare Settings, Jennifer C Spencer, Jane J Kim, Jasmin A Tiro, Sarah J Feldman, Sarah C Kobrin, Celette Sugg Skinner, Lei Wang, Anne Marie Mccarthy, Steve J Atlas, Sandi L Pruitt, Michelle I Silver, Jennifer S Haas Oct 2023

Racial And Ethnic Disparities In Cervical Cancer Screening From Three U.S. Healthcare Settings, Jennifer C Spencer, Jane J Kim, Jasmin A Tiro, Sarah J Feldman, Sarah C Kobrin, Celette Sugg Skinner, Lei Wang, Anne Marie Mccarthy, Steve J Atlas, Sandi L Pruitt, Michelle I Silver, Jennifer S Haas

2020-Current year OA Pubs

INTRODUCTION: This study sought to characterize racial and ethnic disparities in cervical cancer screening and follow-up of abnormal findings across 3 U.S. healthcare settings.

METHODS: Data were from 2016 to 2019 and were analyzed in 2022, reflecting sites within the Multi-level Optimization of the Cervical Cancer Screening Process in Diverse Settings & Populations Research Center, part of the Population-based Research to Optimize the Screening Process consortium, including a safety-net system in the southwestern U.S., a northwestern mixed-model system, and a northeastern integrated healthcare system. Screening uptake was evaluated among average-risk patients (i.e., no previous abnormalities) by race and ethnicity as …


Neratinib + Fulvestrant + Trastuzumab For Hr-Positive, Her2-Negative, Her2-Mutant Metastatic Breast Cancer: Outcomes And Biomarker Analysis From The Summit Trial, K Jhaveri, H Park, C Ma, R Bose, L Peterson, Et Al. Oct 2023

Neratinib + Fulvestrant + Trastuzumab For Hr-Positive, Her2-Negative, Her2-Mutant Metastatic Breast Cancer: Outcomes And Biomarker Analysis From The Summit Trial, K Jhaveri, H Park, C Ma, R Bose, L Peterson, Et Al.

2020-Current year OA Pubs

BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T.

PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + …


The Median Doses Of Beta-Blockers Among Older Adults With Heart Failure With Reduced Ejection Fraction, Min Ji Kwak, Caroline Schaefer, Trudy Millard Krause, Parag Goyal, Dae Hyun Kim, Abhijeet Dhoble, Michael Johnson, Rajender Aparasu, Holly M Holmes Oct 2023

The Median Doses Of Beta-Blockers Among Older Adults With Heart Failure With Reduced Ejection Fraction, Min Ji Kwak, Caroline Schaefer, Trudy Millard Krause, Parag Goyal, Dae Hyun Kim, Abhijeet Dhoble, Michael Johnson, Rajender Aparasu, Holly M Holmes

Faculty, Staff and Student Publications

No abstract provided.


Comparison Of Lotions, Creams, Gels And Ointments For The Treatment Of Childhood Eczema: The Bee Rct, Matthew J Ridd, Sian Wells, Stephanie J Macneill, Emily Sanderson, Douglas Webb, Jonathan Banks, Eileen Sutton, Alison Rg Shaw, Zoe Wilkins, Julie Clayton, Amanda Roberts, Kirsty Garfield, Lyn Liddiard, Tiffany J Barrett, J Athene Lane, Helen Baxter, Laura Howells, Jodi Taylor, Alastair D Hay, Hywel C Williams, Kim S Thomas, Miriam Santer Oct 2023

Comparison Of Lotions, Creams, Gels And Ointments For The Treatment Of Childhood Eczema: The Bee Rct, Matthew J Ridd, Sian Wells, Stephanie J Macneill, Emily Sanderson, Douglas Webb, Jonathan Banks, Eileen Sutton, Alison Rg Shaw, Zoe Wilkins, Julie Clayton, Amanda Roberts, Kirsty Garfield, Lyn Liddiard, Tiffany J Barrett, J Athene Lane, Helen Baxter, Laura Howells, Jodi Taylor, Alastair D Hay, Hywel C Williams, Kim S Thomas, Miriam Santer

Faculty, Staff and Student Publications

BACKGROUND: Emollients are recommended for children with eczema (atopic eczema/dermatitis). A lack of head-to-head comparisons of the effectiveness and acceptability of the different types of emollients has resulted in a 'trial and error' approach to prescribing.

OBJECTIVE: To compare the effectiveness and acceptability of four commonly used types of emollients for the treatment of childhood eczema.

DESIGN: Four group, parallel, individually randomised, superiority randomised clinical trials with a nested qualitative study, completed in 2021. A purposeful sample of parents/children was interviewed at ≈ 4 and ≈ 16 weeks.

SETTING: Primary care (78 general practitioner surgeries) in England.

PARTICIPANTS: Children aged …


Diabetes Risk During Pregnancy Among Second-Generation Immigrants: A National Cohort Study In Sweden, Per Wändell, Xinjun Li, Nouha Saleh Stattin, Axel C Carlsson, Jan Sundquist, Casey Crump, Kristina Sundquist Oct 2023

Diabetes Risk During Pregnancy Among Second-Generation Immigrants: A National Cohort Study In Sweden, Per Wändell, Xinjun Li, Nouha Saleh Stattin, Axel C Carlsson, Jan Sundquist, Casey Crump, Kristina Sundquist

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Gestational diabetes is more common in many first-generation immigrant women in Europe and other Western countries. Less is known about second-generation immigrant women; such knowledge is needed to understand generational influences on diabetes risk. We aimed to study second-generation immigrant women regarding the presence of all types of diabetes during pregnancy.

METHODS AND RESULTS: A cohort study was conducted using the Swedish National Birth Register, the National Patient Register, and the total Population Register. We used Cox regression analysis to compute hazard ratios (HRs) and 99% confidence intervals (99% CI) for any diabetes during pregnancy and specific …