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2023

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Articles 5671 - 5700 of 9378

Full-Text Articles in Medical Specialties

Antibody-Drug Conjugates For Multiple Myeloma: Just The Beginning, Or The Beginning Of The End?, Upasana Ray, Robert Z Orlowski Apr 2023

Antibody-Drug Conjugates For Multiple Myeloma: Just The Beginning, Or The Beginning Of The End?, Upasana Ray, Robert Z Orlowski

Faculty, Staff and Student Publications

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen receptors (CARs) in the B-cell maturation antigen (BCMA)-targeted CAR T-cell products idecabtagene vicleucel and ciltacabtagene autoleucel, which are approved …


Occupational Therapy In End-Of-Life Care, Shannon Sudrla Apr 2023

Occupational Therapy In End-Of-Life Care, Shannon Sudrla

Student Capstone Papers

Patients at the end-of-life (EoL) experience functional decline in response to terminal illness and the active dying process, inhibiting participation and engagement in meaningful daily activities. Occupational therapy practitioners (OTP) are equipped to address patients’ occupational needs and desires despite their declining capacities; however, the absence of occupational therapy (OT) services in EoL care leaves patients’ occupational needs unmet, directly affecting their quality of life. The literature demonstrates the need for enhanced education and training among occupational therapy students (OTS) and practitioners to better prepare them to work with terminally ill patients who face progressive functional decline and imminent death. …


Longitudinal Variations In Antibody Responses Against Sars-Cov-2 Spike Epitopes Upon Serial Vaccinations, Dicle Yalcin, Sydney J. Bennett, Jared Sheehan, Amber J. Trauth, For Yue Tso, John T. West, Michael E. Hagensee, Alistair J. Ramsay, Charles Wood Apr 2023

Longitudinal Variations In Antibody Responses Against Sars-Cov-2 Spike Epitopes Upon Serial Vaccinations, Dicle Yalcin, Sydney J. Bennett, Jared Sheehan, Amber J. Trauth, For Yue Tso, John T. West, Michael E. Hagensee, Alistair J. Ramsay, Charles Wood

School of Medicine Faculty Publications

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted healthcare, the workforce, and worldwide socioeconomics. Multi-dose mono- or bivalent mRNA vaccine regimens have shown high efficacy in protection against SARS-CoV-2 and its emerging variants with varying degrees of efficacy. Amino acid changes, primarily in the receptor-binding domain (RBD), result in selection for viral infectivity, disease severity, and immune evasion. Therefore, many studies have centered around neutralizing antibodies that target the RBD and their generation achieved through infection or vaccination. Here, we conducted a unique longitudinal study, analyzing the effects of a three-dose mRNA vaccine regimen …


Phase Ii Study Of Palbociclib (Pd-0332991) In Ccnd1, 2, Or 3 Amplification: Results From The Nci-Match Ecog-Acrin Trial (Eay131) Subprotocol Z1b, Amy S Clark, Fangxin Hong, Richard S Finn, Angela M Demichele, Edith P. Mitchell, James Zwiebel, Fernanda I Arnaldez, Robert J Gray, Victoria Wang, Lisa M Mcshane, Larry V Rubinstein, David Patton, P Mickey Williams, Stanley R Hamilton, Mehmet S Copur, Samer S Kasbari, Ravneet Thind, Barbara A Conley, Carlos L Arteaga, Peter J O'Dwyer, Lyndsay N Harris, Alice P Chen, Keith T Flaherty Apr 2023

Phase Ii Study Of Palbociclib (Pd-0332991) In Ccnd1, 2, Or 3 Amplification: Results From The Nci-Match Ecog-Acrin Trial (Eay131) Subprotocol Z1b, Amy S Clark, Fangxin Hong, Richard S Finn, Angela M Demichele, Edith P. Mitchell, James Zwiebel, Fernanda I Arnaldez, Robert J Gray, Victoria Wang, Lisa M Mcshane, Larry V Rubinstein, David Patton, P Mickey Williams, Stanley R Hamilton, Mehmet S Copur, Samer S Kasbari, Ravneet Thind, Barbara A Conley, Carlos L Arteaga, Peter J O'Dwyer, Lyndsay N Harris, Alice P Chen, Keith T Flaherty

Department of Medical Oncology Faculty Papers

Purpose: Cyclin D/CDK4/6 is critical in controlling the G1 to S checkpoint. CCND, the gene encoding cyclin D, is known to be amplified in a variety of solid tumors. Palbociclib is an oral CDK4/6 inhibitor, approved in advanced breast cancer in combination with endocrine therapy. We explored the efficacy of palbociclib in patients with nonbreast solid tumors containing an amplification in CCND1, 2, or 3.

Patients and methods: Patients with tumors containing a CCND1, 2, or 3 amplification and expression of the retinoblastoma protein were assigned to subprotocol Z1B and received palbociclib 125 mg once daily for 21 days of …


Antibody-Drug Conjugates For Multiple Myeloma: Just The Beginning, Or The Beginning Of The End?, Upasana Ray, Robert Z Orlowski Apr 2023

Antibody-Drug Conjugates For Multiple Myeloma: Just The Beginning, Or The Beginning Of The End?, Upasana Ray, Robert Z Orlowski

Faculty, Staff and Student Publications

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen receptors (CARs) in the B-cell maturation antigen (BCMA)-targeted CAR T-cell products idecabtagene vicleucel and ciltacabtagene autoleucel, which are approved …


Antibody-Drug Conjugates For Multiple Myeloma: Just The Beginning, Or The Beginning Of The End?, Upasana Ray, Robert Z Orlowski Apr 2023

Antibody-Drug Conjugates For Multiple Myeloma: Just The Beginning, Or The Beginning Of The End?, Upasana Ray, Robert Z Orlowski

Faculty, Staff and Student Publications

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen receptors (CARs) in the B-cell maturation antigen (BCMA)-targeted CAR T-cell products idecabtagene vicleucel and ciltacabtagene autoleucel, which are approved …


Bayesian Adaptive Model Selection Design For Optimal Biological Dose Finding In Phase I/Ii Clinical Trials, Ruitao Lin, Guosheng Yin, Haolun Shi Apr 2023

Bayesian Adaptive Model Selection Design For Optimal Biological Dose Finding In Phase I/Ii Clinical Trials, Ruitao Lin, Guosheng Yin, Haolun Shi

Faculty, Staff and Student Publications

Identification of the optimal dose presents a major challenge in drug development with molecularly targeted agents, immunotherapy, as well as chimeric antigen receptor T-cell treatments. By casting dose finding as a Bayesian model selection problem, we propose an adaptive design by simultaneously incorporating the toxicity and efficacy outcomes to select the optimal biological dose (OBD) in phase I/II clinical trials. Without imposing any parametric assumption or shape constraint on the underlying dose-response curves, we specify curve-free models for both the toxicity and efficacy endpoints to determine the OBD. By integrating the observed data across all dose levels, the proposed design …


The Abscopal Effect In Patients With Cancer Receiving Immunotherapy, Blessie Elizabeth Nelson, Jacob J Adashek, Steven H Lin, Vivek Subbiah Apr 2023

The Abscopal Effect In Patients With Cancer Receiving Immunotherapy, Blessie Elizabeth Nelson, Jacob J Adashek, Steven H Lin, Vivek Subbiah

Faculty, Staff and Student Publications

Interest in the abscopal effect has been rekindled over the past decade with the advent of immunotherapy. Although purportedly elusive, this phenomenon is being increasingly reported. Venturing further using a multimodality approach with an array of systemic agents and unconventional modalities is direly needed. In this perspective, we describe the fundamentals of abscopal responses (ARs), explore combinations with systemic therapies that hold promise in eliciting ARs, and reconnoiter unconventional modalities that may induce ARs. Finally, we scrutinize prospective agents and modalities that exhibit preclinical ability to elicit ARs and discuss prognostic biomarkers, their limitations, and pathways of abscopal resistance for …


Feature Selection For Support Vector Regression Using A Genetic Algorithm, Shannon B Mckearnan, David M Vock, G Elisabeta Marai, Guadalupe Canahuate, Clifton D Fuller, Julian Wolfson Apr 2023

Feature Selection For Support Vector Regression Using A Genetic Algorithm, Shannon B Mckearnan, David M Vock, G Elisabeta Marai, Guadalupe Canahuate, Clifton D Fuller, Julian Wolfson

Faculty, Staff and Student Publications

Support vector regression (SVR) is particularly beneficial when the outcome and predictors are nonlinearly related. However, when many covariates are available, the method's flexibility can lead to overfitting and an overall loss in predictive accuracy. To overcome this drawback, we develop a feature selection method for SVR based on a genetic algorithm that iteratively searches across potential subsets of covariates to find those that yield the best performance according to a user-defined fitness function. We evaluate the performance of our feature selection method for SVR, comparing it to alternate methods including LASSO and random forest, in a simulation study. We …


Mmp9 Clears The Way For Metastatic Cell Penetration Across The Blood-Brain Barrier, Joseph H Mccarty Apr 2023

Mmp9 Clears The Way For Metastatic Cell Penetration Across The Blood-Brain Barrier, Joseph H Mccarty

Faculty, Staff and Student Publications

Although brain metastases are 10-fold more prevalent than primary brain cancers, relatively little is understood about the genes and pathways that promote metastatic cell entry, growth, and survival in the brain. Hence, determining how metastatic tumors colonize the brain and thrive within the neural microenvironment is a topic of both fundamental importance and direct clinical relevance. In this issue, a report by Karreman and colleagues explores pathways that are exploited by metastatic tumor cells to arrest in the circulation, cross the endothelial blood-brain barrier (BBB), and thrive in the brain microenvironment. The authors used elegant imaging tools including intravital fluorescence …


Antibody-Drug Conjugates For Multiple Myeloma: Just The Beginning, Or The Beginning Of The End?, Upasana Ray, Robert Z Orlowski Apr 2023

Antibody-Drug Conjugates For Multiple Myeloma: Just The Beginning, Or The Beginning Of The End?, Upasana Ray, Robert Z Orlowski

Faculty, Staff and Student Publications

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen receptors (CARs) in the B-cell maturation antigen (BCMA)-targeted CAR T-cell products idecabtagene vicleucel and ciltacabtagene autoleucel, which are approved …


Pertuzumab, Trastuzumab, And An Aromatase Inhibitor For Her2-Positive And Hormone Receptor-Positive Metastatic Or Locally Advanced Breast Cancer: Pertain Final Analysis, Grazia Arpino, Juan De La Haba Rodríguez, Jean-Marc Ferrero, Sabino De Placido, C Kent Osborne, Dirk Klingbiel, Valentine Revelant, Christine Wohlfarth, Raf Poppe, Mothaffar F Rimawi Apr 2023

Pertuzumab, Trastuzumab, And An Aromatase Inhibitor For Her2-Positive And Hormone Receptor-Positive Metastatic Or Locally Advanced Breast Cancer: Pertain Final Analysis, Grazia Arpino, Juan De La Haba Rodríguez, Jean-Marc Ferrero, Sabino De Placido, C Kent Osborne, Dirk Klingbiel, Valentine Revelant, Christine Wohlfarth, Raf Poppe, Mothaffar F Rimawi

Faculty, Staff and Students Publications

PURPOSE: In PERTAIN's primary analysis (31 months' median follow-up), adding pertuzumab to trastuzumab and an aromatase inhibitor (AI) with/without chemotherapy significantly improved progression-free survival (PFS) in patients with previously untreated HER2-positive and hormone receptor-positive metastatic or locally advanced breast cancer (M/LABC). A potentially enhanced treatment effect was observed in patients with no induction chemotherapy. We present the final analysis (>6 years' median follow-up).

PATIENTS AND METHODS: Patients (N = 258) were randomized 1:1 to pertuzumab (loading/maintenance: 840/420 mg) plus trastuzumab (loading/maintenance: 8/6 mg/kg) every 3 weeks and an AI (1 mg anastrozole or 2.5 mg letrozole daily; Arm A), …


Pectoralis Nerve Block Compared To Thoracic Paravertebral Nerve Block In The Mastectomy Patient: Evidence-Based Practice Recommendations, Eric Boyer Apr 2023

Pectoralis Nerve Block Compared To Thoracic Paravertebral Nerve Block In The Mastectomy Patient: Evidence-Based Practice Recommendations, Eric Boyer

Doctor of Nursing Practice Scholarly Projects

Patients undergoing a mastectomy are at increased risk of becoming opioid dependent. Most patients undergoing a mastectomy are diagnosed with breast cancer, and the use of opioids is known to aid in cancer metastasizing due to the suppression of the body's natural killer cells. In addition, regional anesthesia, also known as a nerve block, has long provided a reduction in sensation by blocking the nerve pathway, thus numbing the feeling of pain in the operative area. The Pectoralis nerve block (PECS) and the Thoracic Paravertebral block (TPVB) are used in patients undergoing a mastectomy to help reduce the severity of …


Second Annual Research Symposium Program With Abstracts, Office Of Research Affairs, Boonshoft School Of Medicine Apr 2023

Second Annual Research Symposium Program With Abstracts, Office Of Research Affairs, Boonshoft School Of Medicine

Boonshoft School of Medicine Research Symposium

The program booklet is a compilation of abstracts from oral and poster presentations at Wright State University's First Annual Boonshoft School of Medicine Medical Research Symposium held on April 13, 2023.


Intraocular Lens Tilt Due To Optic-Haptic Junction Distortion Following Intrascleral Haptic Fixation With The Yamane Technique, Jordan P. Safran, Steven G. Safran Apr 2023

Intraocular Lens Tilt Due To Optic-Haptic Junction Distortion Following Intrascleral Haptic Fixation With The Yamane Technique, Jordan P. Safran, Steven G. Safran

SKMC Student Presentations and Publications

Purpose: To report two patients with a complication of Yamane intrascleral haptic fixation surgery (ISHF) with the Zeiss CT Lucia 602 lens: severely tilted intraocular lens (IOL) leading to significantly decreased vision in the early post-operative period.

Observations: We report two patients presenting with severely tilted IOL implants one day and one month following Yamane ISHF. The first patient is a monocular 81-year-old woman referred for treatment of cornea edema. Initial surgery involved replacement of an anterior chamber lens with a CT Lucia 602 posterior chamber lens using Yamane technique and Descemet's stripping endothelial keratoplasty. The patient returned at one …


Local Ocular Safety Of The Subconjunctival Injection Of Cetuximab In Rabbits, Hossein Aghaei, Ahmad Kheirkhah, Ali Mohammad Alizadeh, Acieh Es'haghi, Roshanak Aliakbar-Navahi, Zahra Keikha, Samira Chaibakhsh Apr 2023

Local Ocular Safety Of The Subconjunctival Injection Of Cetuximab In Rabbits, Hossein Aghaei, Ahmad Kheirkhah, Ali Mohammad Alizadeh, Acieh Es'haghi, Roshanak Aliakbar-Navahi, Zahra Keikha, Samira Chaibakhsh

Faculty, Staff and Student Publications

BACKGROUND: To evaluate the safety of different doses of subconjunctival cetuximab in rabbits.

METHODS: After general anesthesia rabbits received a subconjunctival injection of 2.5 mg in 0.5 ml, 5 mg in 1 ml, and 10 mg in 2 ml of cetuximab in their right eyes (two rabbits in each group). A similar volume of normal saline solution was injected subconjunctivally in the left eyes. The histopathologic changes were evaluated after enucleation with the aid of H&E staining.

RESULTS: No significant difference were observed between the treated and control eyes in terms of conjunctival inflammation, goblet cell density, or limbal blood …


Psychosocial Interventions Among Patients With Cancer And Their Family Caregivers In The Sub-Saharan Region: A Systematic Review, Ting Guan, Yousef Qan’Ir, Jamie Conklin, Chifundo Colleta Zimba, Agatha Bula, Wongani Jumbo, Kondwani Wella, Patrick Mapulanga, Samuel A.M. Bingo, Evelyn Chilemba, Jennifer Haley, Nilda Peragallo Montano, Ashley Leak Bryant, Lixin Song Apr 2023

Psychosocial Interventions Among Patients With Cancer And Their Family Caregivers In The Sub-Saharan Region: A Systematic Review, Ting Guan, Yousef Qan’Ir, Jamie Conklin, Chifundo Colleta Zimba, Agatha Bula, Wongani Jumbo, Kondwani Wella, Patrick Mapulanga, Samuel A.M. Bingo, Evelyn Chilemba, Jennifer Haley, Nilda Peragallo Montano, Ashley Leak Bryant, Lixin Song

Social Work - All Scholarship

Cancer is becoming a public health issue in the Sub-Saharan Africa (SSA).

This systematic review aims to synthesise psychosocial interventions and

their effects on the health outcomes of adult cancer patients and their

family caregivers in SSA. We identified eligible publications in English

language from PubMed, Cumulative Index of Nursing and Allied Health

Literature Plus with Full Text, Embase, APA PsycInfo, Scopus, and

African Index Medicus databases. We included psychosocial

interventions targeted adult cancer patients/survivors or their family

caregivers in SSA. This review identified five psychosocial interventions

from six studies that support adult cancer patients and their family

caregivers in …


Spdef Modulates Transcriptional Output To Regulate Multiple Pathways: Immune And Inflammatory Pathways As Potential Hubs Targeted By Spdef In Rcc 7/T Cells, A Line Of Prostate Cancer Cells Of African American Origin, Mousa Vatanmakanian, Sweaty Koul, Hari Koul Apr 2023

Spdef Modulates Transcriptional Output To Regulate Multiple Pathways: Immune And Inflammatory Pathways As Potential Hubs Targeted By Spdef In Rcc 7/T Cells, A Line Of Prostate Cancer Cells Of African American Origin, Mousa Vatanmakanian, Sweaty Koul, Hari Koul

School of Graduate Studies Faculty Publications

DiscoverBMB, March 25 - 28, 2023, Seattle, WA


Differences In The Academic Attributes Of Matched And Unmatched Orthopaedic Surgery Residency Applicants Are Narrowing, Suleiman Y. Sudah, Nareena Imam, Francis Sirch, Allen D. Nicholson, Surena Namdari, Mariano E. Menendez Apr 2023

Differences In The Academic Attributes Of Matched And Unmatched Orthopaedic Surgery Residency Applicants Are Narrowing, Suleiman Y. Sudah, Nareena Imam, Francis Sirch, Allen D. Nicholson, Surena Namdari, Mariano E. Menendez

Rothman Institute Papers

Background: Orthopaedic surgery remains one of the most competitive residency specialties, with the number of applicants outpacing the availability of residency positions each year. The purpose of this study was to analyze present-day orthopaedic surgery match data, identify differences between matched and unmatched applicants, and compare our findings to previous trends.

Methods: Applicant data from the National Resident Matching Program from 2016 to 2022 were analyzed. The number of matched and unmatched US allopathic senior orthopaedic applicants relative to the number of available positions was used to determine respective match rates. Performance metrics and applicant characteristics were compared by match …


Mechanisms Of Response And Resistance To Combined Decitabine And Ipilimumab For Advanced Myeloid Disease, Livius Penter, Yang Liu, Jacquelyn O Wolff, Lin Yang, Len Taing, Aashna Jhaveri, Jackson Southard, Manishkumar Patel, Nicole M Cullen, Kathleen L Pfaff, Nicoletta Cieri, Giacomo Oliveira, Seunghee Kim-Schulze, Srinika Ranasinghe, Rebecca Leonard, Taylor Robertson, Elizabeth A Morgan, Helen X Chen, Minkyung H Song, Magdalena Thurin, Shuqiang Li, Scott J Rodig, Carrie Cibulskis, Stacey Gabriel, Pavan Bachireddy, Jerome Ritz, Howard Streicher, Donna S Neuberg, F Stephen Hodi, Matthew S Davids, Sacha Gnjatic, Kenneth J Livak, Jennifer Altreuter, Franziska Michor, Robert J Soiffer, Jacqueline S Garcia, Catherine J Wu Apr 2023

Mechanisms Of Response And Resistance To Combined Decitabine And Ipilimumab For Advanced Myeloid Disease, Livius Penter, Yang Liu, Jacquelyn O Wolff, Lin Yang, Len Taing, Aashna Jhaveri, Jackson Southard, Manishkumar Patel, Nicole M Cullen, Kathleen L Pfaff, Nicoletta Cieri, Giacomo Oliveira, Seunghee Kim-Schulze, Srinika Ranasinghe, Rebecca Leonard, Taylor Robertson, Elizabeth A Morgan, Helen X Chen, Minkyung H Song, Magdalena Thurin, Shuqiang Li, Scott J Rodig, Carrie Cibulskis, Stacey Gabriel, Pavan Bachireddy, Jerome Ritz, Howard Streicher, Donna S Neuberg, F Stephen Hodi, Matthew S Davids, Sacha Gnjatic, Kenneth J Livak, Jennifer Altreuter, Franziska Michor, Robert J Soiffer, Jacqueline S Garcia, Catherine J Wu

Faculty, Staff and Student Publications

The challenge of eradicating leukemia in patients with acute myelogenous leukemia (AML) after initial cytoreduction has motivated modern efforts to combine synergistic active modalities including immunotherapy. Recently, the ETCTN/CTEP 10026 study tested the combination of the DNA methyltransferase inhibitor decitabine together with the immune checkpoint inhibitor ipilimumab for AML/myelodysplastic syndrome (MDS) either after allogeneic hematopoietic stem cell transplantation (HSCT) or in the HSCT-naïve setting. Integrative transcriptome-based analysis of 304 961 individual marrow-infiltrating cells for 18 of 48 subjects treated on study revealed the strong association of response with a high baseline ratio of T to AML cells. Clinical responses were …


Exploring Hapi Incidence In Patients Admitted Through The Ed: A Quality Improvement Initiative, Alexa L. Tietgens Apr 2023

Exploring Hapi Incidence In Patients Admitted Through The Ed: A Quality Improvement Initiative, Alexa L. Tietgens

DNP Projects

Each year in the U.S., pressure injuries, or PIs, are responsible for more than 60,000 patient deaths and billions of dollars’ worth of treatment costs. Research shows that roughly 95% of all PIs are preventable by following evidence-based practice guidelines which include early identification of patients at risk, frequent skin assessments, and implementation of prevention strategies. However, the ED environment creates unique risks for PI development due to the routine use of hard surfaces (i.e., stretchers, backboards, exam tables) and frequent hospital overcrowding. Although nurses play a pivotal role in PI prevention, frequent staffing shortages, high patient acuity levels, and …


A Reduced Pancreatic Polypeptide Response Is Associated With New-Onset Pancreatogenic Diabetes Versus Type 2 Diabetes, Phil A Hart, Yogish C Kudva, Dhiraj Yadav, Dana K Andersen, Yisheng Li, Frederico G S Toledo, Fuchenchu Wang, Melena D Bellin, David Bradley, Randall E Brand, Kenneth Cusi, William Fisher, Kieren Mather, Walter G Park, Zeb Saeed, Robert V Considine, Sarah C Graham, Jo Ann Rinaudo, Jose Serrano, Mark O Goodarzi Apr 2023

A Reduced Pancreatic Polypeptide Response Is Associated With New-Onset Pancreatogenic Diabetes Versus Type 2 Diabetes, Phil A Hart, Yogish C Kudva, Dhiraj Yadav, Dana K Andersen, Yisheng Li, Frederico G S Toledo, Fuchenchu Wang, Melena D Bellin, David Bradley, Randall E Brand, Kenneth Cusi, William Fisher, Kieren Mather, Walter G Park, Zeb Saeed, Robert V Considine, Sarah C Graham, Jo Ann Rinaudo, Jose Serrano, Mark O Goodarzi

Faculty, Staff and Student Publications

PURPOSE: Pancreatogenic diabetes refers to diabetes mellitus (DM) that develops in the setting of a disease of the exocrine pancreas, including pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). We sought to evaluate whether a blunted nutrient response of pancreatic polypeptide (PP) can differentiate these DM subtypes from type 2 DM (T2DM).

METHODS: Subjects with new-onset DM (<3 >years' duration) in the setting of PDAC (PDAC-DM, n = 28), CP (CP-DM, n = 38), or T2DM (n = 99) completed a standardized mixed meal tolerance test, then serum PP concentrations were subsequently measured at a central laboratory. Two-way comparisons of …


Pancreatic Cancer: Advances And Challenges, Christopher J Halbrook, Costas A Lyssiotis, Marina Pasca Di Magliano, Anirban Maitra Apr 2023

Pancreatic Cancer: Advances And Challenges, Christopher J Halbrook, Costas A Lyssiotis, Marina Pasca Di Magliano, Anirban Maitra

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers. Significant efforts have largely defined major genetic factors driving PDAC pathogenesis and progression. Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche. In this review, we highlight the foundational studies that have driven our understanding of these processes. We further discuss the recent technological advances that continue to expand our understanding of PDAC complexity. We posit that the clinical translation of these research endeavors will enhance the currently dismal survival rate of this recalcitrant …


Identification Of Small Extracellular Vesicle Protein Biomarkers For Pediatric Ewing Sarcoma., Soumya M. Turaga, Mihaela E. Sardiu, Vikalp Vishwakarma, Amrita Mitra, Leonidas E. Bantis, Rashna Madan, Michael L. Merchant, Jon B. Klein, Glenson Samuel, Andrew K. Godwin Apr 2023

Identification Of Small Extracellular Vesicle Protein Biomarkers For Pediatric Ewing Sarcoma., Soumya M. Turaga, Mihaela E. Sardiu, Vikalp Vishwakarma, Amrita Mitra, Leonidas E. Bantis, Rashna Madan, Michael L. Merchant, Jon B. Klein, Glenson Samuel, Andrew K. Godwin

Manuscripts, Articles, Book Chapters and Other Papers

Ewing Sarcoma (EWS) is the second most common osseous malignancy in children and young adults after osteosarcoma, while it is the fifth common osseous malignancy within adult age population. The clinical presentation of EWS is quite often non-specific, with the most common symptoms at presentation consisting of pain, swelling or general discomfort. The dearth of clinically relevant diagnostic or predictive biomarkers continues to remain a pressing clinical challenge. Identification of tumor specific biomarkers can lend towards an early diagnosis, expedited initiation of therapy, monitoring of therapeutic response, and early detection of recurrence of disease. We carried-out a complex analysis of …


Immune Checkpoint Therapy-Current Perspectives And Future Directions, Padmanee Sharma, Sangeeta Goswami, Deblina Raychaudhuri, Bilal A Siddiqui, Pratishtha Singh, Ashwat Nagarajan, Jielin Liu, Sumit K Subudhi, Candice Poon, Kristal L Gant, Shelley M Herbrich, Swetha Anandhan, Shajedul Islam, Moran Amit, Gayathri Anandappa, James P Allison Apr 2023

Immune Checkpoint Therapy-Current Perspectives And Future Directions, Padmanee Sharma, Sangeeta Goswami, Deblina Raychaudhuri, Bilal A Siddiqui, Pratishtha Singh, Ashwat Nagarajan, Jielin Liu, Sumit K Subudhi, Candice Poon, Kristal L Gant, Shelley M Herbrich, Swetha Anandhan, Shajedul Islam, Moran Amit, Gayathri Anandappa, James P Allison

Faculty, Staff and Student Publications

Immune checkpoint therapy (ICT) has dramatically altered clinical outcomes for cancer patients and conferred durable clinical benefits, including cure in a subset of patients. Varying response rates across tumor types and the need for predictive biomarkers to optimize patient selection to maximize efficacy and minimize toxicities prompted efforts to unravel immune and non-immune factors regulating the responses to ICT. This review highlights the biology of anti-tumor immunity underlying response and resistance to ICT, discusses efforts to address the current challenges with ICT, and outlines strategies to guide the development of subsequent clinical trials and combinatorial efforts with ICT.


The Role Of Extracellular Vesicles In Cancer, Raghu Kalluri, Kathleen M Mcandrews Apr 2023

The Role Of Extracellular Vesicles In Cancer, Raghu Kalluri, Kathleen M Mcandrews

Faculty, Staff and Student Publications

Intercellular communication is a key feature of cancer progression and metastasis. Extracellular vesicles (EVs) are generated by all cells, including cancer cells, and recent studies have identified EVs as key mediators of cell-cell communication via packaging and transfer of bioactive constituents to impact the biology and function of cancer cells and cells of the tumor microenvironment. Here, we review recent advances in understanding the functional contribution of EVs to cancer progression and metastasis, as cancer biomarkers, and the development of cancer therapeutics.


Targeting Mirnas And Other Non-Coding Rnas As A Therapeutic Approach: An Update, Emine Bayraktar, Recep Bayraktar, Hulya Oztatlici, Gabriel Lopez-Berestein, Paola Amero, Cristian Rodriguez-Aguayo Apr 2023

Targeting Mirnas And Other Non-Coding Rnas As A Therapeutic Approach: An Update, Emine Bayraktar, Recep Bayraktar, Hulya Oztatlici, Gabriel Lopez-Berestein, Paola Amero, Cristian Rodriguez-Aguayo

Faculty, Staff and Student Publications

Since the discovery of the first microRNAs (miRNAs, miRs), the understanding of miRNA biology has expanded substantially. miRNAs are involved and described as master regulators of the major hallmarks of cancer, including cell differentiation, proliferation, survival, the cell cycle, invasion, and metastasis. Experimental data indicate that cancer phenotypes can be modified by targeting miRNA expression, and because miRNAs act as tumor suppressors or oncogenes (oncomiRs), they have emerged as attractive tools and, more importantly, as a new class of targets for drug development in cancer therapeutics. With the use of miRNA mimics or molecules targeting miRNAs (i.e., small-molecule inhibitors such …


Targeting Of Epigenetic Co-Dependencies Enhances Anti-Aml Efficacy Of Menin Inhibitor In Aml With Mll1-R Or Mutant Npm1, Warren Fiskus, Christopher P Mill, Christine Birdwell, John A Davis, Kaberi Das, Steffen Boettcher, Tapan M Kadia, Courtney D Dinardo, Koichi Takahashi, Sanam Loghavi, Michael J Soth, Tim Heffernan, Gerard M Mcgeehan, Xinjia Ruan, Xiaoping Su, Christopher R Vakoc, Naval Daver, Kapil N Bhalla Apr 2023

Targeting Of Epigenetic Co-Dependencies Enhances Anti-Aml Efficacy Of Menin Inhibitor In Aml With Mll1-R Or Mutant Npm1, Warren Fiskus, Christopher P Mill, Christine Birdwell, John A Davis, Kaberi Das, Steffen Boettcher, Tapan M Kadia, Courtney D Dinardo, Koichi Takahashi, Sanam Loghavi, Michael J Soth, Tim Heffernan, Gerard M Mcgeehan, Xinjia Ruan, Xiaoping Su, Christopher R Vakoc, Naval Daver, Kapil N Bhalla

Faculty, Staff and Student Publications

Monotherapy with Menin inhibitor (MI), e.g., SNDX-5613, induces clinical remissions in patients with relapsed/refractory AML harboring MLL1-r or mtNPM1, but most patients either fail to respond or eventually relapse. Utilizing single-cell RNA-Seq, ChiP-Seq, ATAC-Seq, RNA-Seq, RPPA, and mass cytometry (CyTOF) analyses, present pre-clinical studies elucidate gene-expression correlates of MI efficacy in AML cells harboring MLL1-r or mtNPM1. Notably, MI-mediated genome-wide, concordant, log2 fold-perturbations in ATAC-Seq and RNA-Seq peaks were observed at the loci of MLL-FP target genes, with upregulation of mRNAs associated with AML differentiation. MI treatment also reduced the number of AML cells expressing the stem/progenitor cell signature. A …


Experiential Exposure As The Key To Recruiting Medical Students Into Pathology, Ashley M. Holloman, Mary P. Berg, Bronwyn Bryant, Lisa Ross Dixson, Melissa R. George, Julie Katz Karp, Barbara E.C. Knollmann-Ritschel, Victor Gerardo Prieto, Charles F. Timmons, John Michael Childs, Amanda Lofgreen, Kristen Johnson, Cindy B. Mccloskey Apr 2023

Experiential Exposure As The Key To Recruiting Medical Students Into Pathology, Ashley M. Holloman, Mary P. Berg, Bronwyn Bryant, Lisa Ross Dixson, Melissa R. George, Julie Katz Karp, Barbara E.C. Knollmann-Ritschel, Victor Gerardo Prieto, Charles F. Timmons, John Michael Childs, Amanda Lofgreen, Kristen Johnson, Cindy B. Mccloskey

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

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


How Influential Are Medical School Curriculum And Other Medical School Characteristics In Students’ Selecting Pathology As A Specialty?, Cindy B. Mccloskey, Mark Brissette, John Michael Childs, Amanda Lofgreen, Kristen Johnson, Melissa R. George, Ashley M. Holloman, Bronwyn Bryant, Mary P. Berg, Lisa Ross Dixon, Julie Katz Karp, Barbara E.C. Knollmann-Ritschel, Victor Gerardo Prieto, Charles F. Timmons, Robert D. Hoffman Apr 2023

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

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

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