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Full-Text Articles in Neoplasms

Risk Factors Associated With Patient-Reported Fatigue Among Long-Term Oropharyngeal Carcinoma Survivors, Puja Aggarwal, Katherine A Hutcheson, Ryan P Goepfert, Adam S Garden, Naveen Garg, Frank E Mott, Clifton D Fuller, Stephen Y Lai, Gary Brandon Gunn, Mark S Chambers, Ehab Y Hanna, Erich M Sturgis, Sanjay Shete Apr 2022

Risk Factors Associated With Patient-Reported Fatigue Among Long-Term Oropharyngeal Carcinoma Survivors, Puja Aggarwal, Katherine A Hutcheson, Ryan P Goepfert, Adam S Garden, Naveen Garg, Frank E Mott, Clifton D Fuller, Stephen Y Lai, Gary Brandon Gunn, Mark S Chambers, Ehab Y Hanna, Erich M Sturgis, Sanjay Shete

Faculty, Staff and Students Publications

BACKGROUND: The study objective is to identify risk factors associated with fatigue among long-term OPC survivors.

METHODS: This cross-sectional study included disease-free OPC survivors treated curatively between 2000 and 2013 who were surveyed from September 2015 to July 2016. The outcome variable was patient-reported fatigue. Multivariable logistic regression was used to identify factors associated with moderate to severe fatigue.

RESULTS: Among 863 OPC survivors, 17.4% reported moderate to severe fatigue. Self-reported thyroid problems (OR: 2.01; p = 0.003), current cigarette smoking at time of survey (OR: 3.85; p = 0.001), late lower cranial neuropathy (OR: 3.44; p = 0.002), and …


A Multi-Disciplinary Approach To Chronic Cough In Children, Shraddha S Mukerji, Naga Jaya Smitha Yenduri, Eric Chiou, Siby P Moonnumakal, Joshua R Bedwell Apr 2022

A Multi-Disciplinary Approach To Chronic Cough In Children, Shraddha S Mukerji, Naga Jaya Smitha Yenduri, Eric Chiou, Siby P Moonnumakal, Joshua R Bedwell

Faculty, Staff and Students Publications

OBJECTIVES: (1) To highlight the important causes of chronic and recurrent cough in children. (2) To discuss multidisciplinary approach to management of chronic/recurrent pediatric cough.

METHODS: Review of scholarly articles, guidelines, expert panels via PubMed and Google Scholar.

CONCLUSION: Chronic cough (CC) in children is mainly attributed to persistent bacterial bronchitis, asthma, nonspecific cough, and gastroesophageal reflux disease (GERD) symptoms. A multi-disciplinary approach is cost-effective and aids with earlier diagnosis and appropriate treatment. Congenital or acquired narrowing of the subglottis is the leading ENT cause for recurrent croup (RC) in children. Laryngeal cleft-type 1 is commonly seen in children with …


Differences In Covid-19-Related Testing And Healthcare Utilization By Race And Ethnicity In The Veterans Health Administration, Javad Razjouyan, Drew A Helmer, Ang Li, Aanand D Naik, Christopher I Amos, Venkata Bandi, Amir Sharafkhaneh Apr 2022

Differences In Covid-19-Related Testing And Healthcare Utilization By Race And Ethnicity In The Veterans Health Administration, Javad Razjouyan, Drew A Helmer, Ang Li, Aanand D Naik, Christopher I Amos, Venkata Bandi, Amir Sharafkhaneh

Faculty, Staff and Students Publications

IMPORTANCE: Recent reports indicate differences in COVID-19-related care and outcomes between Black and White Americans.

OBJECTIVE: We examine the COVID-19-related healthcare utilization and mortality by race and ethnicity of patients tested for SARS-CoV-2 in the Veterans Health Administration (VHA).

DESIGN: A retrospective cohort study.

SETTING: We used the VHA COVID-19 shared data resources between February 1 and June 30, 2020.

PARTICIPANTS: Veterans tested for SARS-CoV-2 virus by VHA.

EXPOSURE(S): Three racial-ethnicity groups of Black, Hispanic, and White (as reference) veterans.

MAIN OUTCOME(S) AND MEASURE(S): Main outcomes are testing rate, positivity rate, hospitalization rate, ICU admission rate, and in-hospital mortality. Controlling …


Breast And Prostate Cancer Screening: Recommendations From The American Cancer Society Versus The U.S. Preventive Services Task Force, Eric Chung, Elizabeth Kramer, Katlyn Brown, Farabi Alam, Olivia Henton, Natalie Dipietro Mager Mar 2022

Breast And Prostate Cancer Screening: Recommendations From The American Cancer Society Versus The U.S. Preventive Services Task Force, Eric Chung, Elizabeth Kramer, Katlyn Brown, Farabi Alam, Olivia Henton, Natalie Dipietro Mager

Pharmacy and Wellness Review

Over the past decades, opportunities for pharmacists to be actively involved in screening, education and referral for patients have grown. As these opportunities have increased, so too has the importance of being knowledgeable about the corresponding recommendations and guidelines. At times, various expert organizations may publish contradicting guidelines for a particular disease state or preventive medicine recommendation. This article focuses on the general background and history of two such expert groups, the American Cancer Society and the U.S. Preventive Services Task Force, and compares the two entities’ recommendations for breast and prostate cancer as of April 2017. It is critical …


Synergy Of Venetoclax And 8-Chloro-Adenosine In Aml: The Interplay Of Rrna Inhibition And Fatty Acid Metabolism, Dinh Hoa Hoang, Corey Morales, Ivan Rodriguez Rodriguez, Melissa Valerio, Jiamin Guo, Min-Hsuan Chen, Xiwei Wu, David Horne, Varsha Gandhi, Lisa S Chen, Bin Zhang, Vinod Pullarkat, Steven T Rosen, Guido Marcucci, Ralf Buettner, Le Xuan Truong Nguyen Mar 2022

Synergy Of Venetoclax And 8-Chloro-Adenosine In Aml: The Interplay Of Rrna Inhibition And Fatty Acid Metabolism, Dinh Hoa Hoang, Corey Morales, Ivan Rodriguez Rodriguez, Melissa Valerio, Jiamin Guo, Min-Hsuan Chen, Xiwei Wu, David Horne, Varsha Gandhi, Lisa S Chen, Bin Zhang, Vinod Pullarkat, Steven T Rosen, Guido Marcucci, Ralf Buettner, Le Xuan Truong Nguyen

Faculty, Staff and Student Publications

It is known that 8-chloro-adenosine (8-Cl-Ado) is a novel RNA-directed nucleoside analog that targets leukemic stem cells (LSCs). In a phase I clinical trial with 8-Cl-Ado in patients with refractory or relapsed (R/R) AML, we observed encouraging but short-lived clinical responses, likely due to intrinsic mechanisms of LSC resistance. LSC homeostasis depends on amino acid-driven and/or fatty acid oxidation (FAO)-driven oxidative phosphorylation (OXPHOS) for survival. We recently reported that 8-Cl-Ado and the BCL-2-selective inhibitor venetoclax (VEN) synergistically inhibit FAO and OXPHOS in LSCs, thereby suppressing acute myeloid leukemia (AML) growth in vitro and in vivo. Herein, we report that 8-Cl-Ado …


Depletion Of Transmembrane Mucin 4 (Muc4) Alters Intestinal Homeostasis In A Genetically Engineered Mouse Model Of Colorectal Cancer, Ramesh Pothuraju, Priya Pai, Sanjib Chaudhary, Jawed A Siddiqui, Jesse L Cox, Sukhwinder Kaur, Satyanarayana Rachagani, Hemant K Roy, Michael Bouvet, Surinder K Batra Mar 2022

Depletion Of Transmembrane Mucin 4 (Muc4) Alters Intestinal Homeostasis In A Genetically Engineered Mouse Model Of Colorectal Cancer, Ramesh Pothuraju, Priya Pai, Sanjib Chaudhary, Jawed A Siddiqui, Jesse L Cox, Sukhwinder Kaur, Satyanarayana Rachagani, Hemant K Roy, Michael Bouvet, Surinder K Batra

Faculty, Staff and Students Publications

Mucins are components of the mucus layer overlying the intestinal epithelial cells, which maintains physiological homeostasis. Altered mucin expression is associated with disease progression. Expression of MUC4 decreases in colorectal cancer (CRC); however, its functional role and implications in the intestinal pathology in CRC are not studied well. Therefore, we generated a genetically engineered Muc4 knockout (Muc4-/-) CRC mouse model by crossing with Muc4-/- and Apcflox/flox mice in the presence of colon-specific inducible Cre. We observed that deficiency of Muc4 results in an increased number of macroscopic tumors in the colon and rectal region and leads to poor survival. …


Of Vascular Defense, Hemostasis, Cancer, And Platelet Biology: An Evolutionary Perspective, David G Menter, Vahid Afshar-Kharghan, John Paul Shen, Stephanie L Martch, Anirban Maitra, Scott Kopetz, Kenneth V Honn, Anil K Sood Mar 2022

Of Vascular Defense, Hemostasis, Cancer, And Platelet Biology: An Evolutionary Perspective, David G Menter, Vahid Afshar-Kharghan, John Paul Shen, Stephanie L Martch, Anirban Maitra, Scott Kopetz, Kenneth V Honn, Anil K Sood

Faculty, Staff and Student Publications

We have established considerable expertise in studying the role of platelets in cancer biology. From this expertise, we were keen to recognize the numerous venous-, arterial-, microvascular-, and macrovascular thrombotic events and immunologic disorders are caused by severe, acute-respiratory-syndrome coronavirus 2 (SARS-CoV-2) infections. With this offering, we explore the evolutionary connections that place platelets at the center of hemostasis, immunity, and adaptive phylogeny. Coevolutionary changes have also occurred in vertebrate viruses and their vertebrate hosts that reflect their respective evolutionary interactions. As mammals adapted from aquatic to terrestrial life and the heavy blood loss associated with placentalization-based live birth, platelets …


Otosyphilis: A Rare Cause Of Reversible Hearing Loss In A Teenage Male, Shan He, Anna H Messner, Gayatri Mirani Mar 2022

Otosyphilis: A Rare Cause Of Reversible Hearing Loss In A Teenage Male, Shan He, Anna H Messner, Gayatri Mirani

Faculty, Staff and Students Publications

A high index of suspicion and a thorough neurotologic examination at the onset of presentation are imperative to generate the diagnosis of otosyphilis. Complete audiologic recovery is rare but possible in approximately 20%-25% of patients after appropriate treatment. We present a case of reversible hearing loss secondary to otosyphilis in a teenage male patient with a new diagnosis of human immunodeficiency virus (HIV). Audiology findings were consistent with mixed hearing loss. Lumbar puncture results were consistent with neurosyphilis. Prompt treatment with a 14-day course of intravenous penicillin led to the complete recovery of hearing. In this case report, the pathophysiology, …


Diagnostic Accuracy Of Axillary Nodal Ultrasound After Neoadjuvant Chemotherapy In Node-Positive Breast Cancer Patients: A Validation Study, Syeda Sakina Abidi, Lubna Mushtaque Vohra, Asad Ali Kerawala, Imrana Masroor, Muhammad Umair Tahseen Feb 2022

Diagnostic Accuracy Of Axillary Nodal Ultrasound After Neoadjuvant Chemotherapy In Node-Positive Breast Cancer Patients: A Validation Study, Syeda Sakina Abidi, Lubna Mushtaque Vohra, Asad Ali Kerawala, Imrana Masroor, Muhammad Umair Tahseen

Section of General Surgery

Objective: To determine the accuracy and false negative rate of axillary ultrasound compared to sentinel node biopsy.
Methods: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, from February 1 to March 31, 2021, and comprised data of breast cancer patients who had undergone neo-adjuvant chemotherapy followed by axillary lymph node dissection or axillary disease diagnosed using lymph node biopsy or sentinel lymph node biopsy between January 1, 2016, and December 30, 2020. After receiving neoadjuvant chemotherapy, axillary ultrasound findings were compared with histopathology of lymph nodes. Data was analysed using SPSS 22.
Results: Of the 155 …


Pulmonary Adenoid Cystic Carcinoma Presenting Late With Intrapericardial Extension: Case Report, Manzar Abbas, Usama Qamar, Syeda Maria Ahmad Zaidi, Faiqa Binte Aamir, Ali Aahil Noorali, Haseeb Ur Rahman, Saulat Hasnain Fatimi Feb 2022

Pulmonary Adenoid Cystic Carcinoma Presenting Late With Intrapericardial Extension: Case Report, Manzar Abbas, Usama Qamar, Syeda Maria Ahmad Zaidi, Faiqa Binte Aamir, Ali Aahil Noorali, Haseeb Ur Rahman, Saulat Hasnain Fatimi

Medical College Documents

Adenoid cystic carcinoma, also known as cylindroma, is one of the rare and unexplored clinical presentations of lung cancer, for which existing knowledge is scarce. This case report discusses a presentation of this tumor in the right lung, which subsequently extended to the left atrium through the right superior pulmonary vein. The extension of this rare tumor into the left atrium makes this case both uniquely distinctive and clinically relevant. The management strategy opted for this case was a right posterolateral thoracotomy and right pneumonectomy with partial resection of the left atrium. The desired outcome of this report is to …


Randomized Phase Iii Bmt Ctn Trial Of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions In Myeloablative Hematopoietic Cell Transplantation For Hematologic Malignancies, Leo Luznik, Marcelo C Pasquini, Brent Logan, Robert J Soiffer, Juan Wu, Steven M Devine, Nancy Geller, Sergio Giralt, Helen E Heslop, Mary M Horowitz, Richard J Jones, Mark R Litzow, Adam Mendizabal, Lori Muffly, Eneida R Nemecek, Lynn O'Donnell, Richard J O'Reilly, Raquel Palencia, Johannes Schetelig, Leyla Shune, Scott R Solomon, Sumithira Vasu, Vincent T Ho, Miguel-Angel Perales Feb 2022

Randomized Phase Iii Bmt Ctn Trial Of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions In Myeloablative Hematopoietic Cell Transplantation For Hematologic Malignancies, Leo Luznik, Marcelo C Pasquini, Brent Logan, Robert J Soiffer, Juan Wu, Steven M Devine, Nancy Geller, Sergio Giralt, Helen E Heslop, Mary M Horowitz, Richard J Jones, Mark R Litzow, Adam Mendizabal, Lori Muffly, Eneida R Nemecek, Lynn O'Donnell, Richard J O'Reilly, Raquel Palencia, Johannes Schetelig, Leyla Shune, Scott R Solomon, Sumithira Vasu, Vincent T Ho, Miguel-Angel Perales

Faculty, Staff and Students Publications

PURPOSE: Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD).

METHODS: This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or …


Head And Neck Cancer Survivorship Consensus Statement From The American Head And Neck Society, Neerav Goyal, Andrew Day, Joel Epstein, Joseph Goodman, Evan Graboyes, Scharukh Jalisi, Ana P Kiess, Jamie A Ku, Matthew C Miller, Aru Panwar, Vijay A Patel, Assuntina Sacco, Vlad Sandulache, Amy M Williams, Daniel Deschler, D Gregory Farwell, Cherie-Ann Nathan, Carole Fakhry, Nishant Agrawal Feb 2022

Head And Neck Cancer Survivorship Consensus Statement From The American Head And Neck Society, Neerav Goyal, Andrew Day, Joel Epstein, Joseph Goodman, Evan Graboyes, Scharukh Jalisi, Ana P Kiess, Jamie A Ku, Matthew C Miller, Aru Panwar, Vijay A Patel, Assuntina Sacco, Vlad Sandulache, Amy M Williams, Daniel Deschler, D Gregory Farwell, Cherie-Ann Nathan, Carole Fakhry, Nishant Agrawal

Faculty, Staff and Students Publications

OBJECTIVES: To provide a consensus statement describing best practices and evidence regarding head and neck cancer survivorship.

METHODS: Key topics regarding head and neck cancer survivorship were identified by the multidisciplinary membership of the American Head and Neck Society Survivorship, Supportive Care & Rehabilitation Service. Guidelines were generated by combining expert opinion and a review of the literature and categorized by level of evidence.

RESULTS: Several areas regarding survivorship including dysphonia, dysphagia, fatigue, chronic pain, intimacy, the ability to return to work, financial toxicity, lymphedema, psycho-oncology, physical activity, and substance abuse were identified and discussed. Additionally, the group identified and …


Allogeneic Transplant And Car-T Therapy After Autologous Transplant Failure In Dlbcl: A Noncomparative Cohort Analysis, Mehdi Hamadani, Ajay K Gopal, Marcelo Pasquini, Soyoung Kim, Xianmiao Qiu, Sairah Ahmed, Aleksandr Lazaryan, Vijaya Raj Bhatt, Andrew Daly, Premal Lulla, Stefan Ciurea, Jordan Gauthier, Vaibhav Agrawal, Natalie S Grover, Lazaros Lekakis, Dipenkumar Modi, Parastoo B Dahi, Megan M Herr, P Connor Johnson, Hamza Hashmi, Peiman Hematti, Frederick L Locke Jan 2022

Allogeneic Transplant And Car-T Therapy After Autologous Transplant Failure In Dlbcl: A Noncomparative Cohort Analysis, Mehdi Hamadani, Ajay K Gopal, Marcelo Pasquini, Soyoung Kim, Xianmiao Qiu, Sairah Ahmed, Aleksandr Lazaryan, Vijaya Raj Bhatt, Andrew Daly, Premal Lulla, Stefan Ciurea, Jordan Gauthier, Vaibhav Agrawal, Natalie S Grover, Lazaros Lekakis, Dipenkumar Modi, Parastoo B Dahi, Megan M Herr, P Connor Johnson, Hamza Hashmi, Peiman Hematti, Frederick L Locke

Faculty, Staff and Students Publications

Allogeneic transplant (alloHCT) and chimeric antigen receptor modified (CAR)-T cell therapy are potentially cuarative options of diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous (auto)HCT. Although the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic model can predict outcomes of alloHCT in DLBCL after autoHCT failure, corresponding models of CAR-T treatment in similar patient populations are not available. In this noncomparative registry analysis, we report outcomes of patients with DLBCL (≥18 years) undergoing a reduced intensity alloHCT or CAR-T therapy with axicabtagene ciloleucel during 2012 to 2019 after a prior auto-HCT failure and apply the CIBMTR prognostic …


Differences In Health-Related Outcomes And Health Care Resource Utilization In Breast Cancer Survivors With And Without Type 2 Diabetes, Susan Storey, Zuoyi Zhang, Xiao Luo, Megan Metzger, Amrutha Ravali Jakka, Kun Huang, Diane Von Ah Jan 2022

Differences In Health-Related Outcomes And Health Care Resource Utilization In Breast Cancer Survivors With And Without Type 2 Diabetes, Susan Storey, Zuoyi Zhang, Xiao Luo, Megan Metzger, Amrutha Ravali Jakka, Kun Huang, Diane Von Ah

Journal of Patient-Centered Research and Reviews

Purpose: Up to 74% of breast cancer survivors (BCS) have at least one preexisting comorbid condition, with diabetes (type 2) common. The purpose of this study was to examine differences in health-related outcomes (anemia, neutropenia, and infection) and utilization of health care resources (inpatient, outpatient, and emergency visits) in BCS with and without diabetes.

Methods: In this retrospective cohort study, data were leveraged from the electronic health records of a large health network linked to the Indiana State Cancer Registry. BCS diagnosed between January 2007 and December 2017 and who had received chemotherapy were included. Multivariable logistic regression and generalized …


The Efficacy And Safety Of Thrombopoietin Receptor Agonists In Patients With Chronic Liver Disease Undergoing Elective Procedures: A Systematic Review And Meta-Analysis, Ingrid Lindquist, Sven R Olson, Ang Li, Hanny Al-Samkari, Janice H Jou, Owen J T Mccarty, Joseph J Shatzel Jan 2022

The Efficacy And Safety Of Thrombopoietin Receptor Agonists In Patients With Chronic Liver Disease Undergoing Elective Procedures: A Systematic Review And Meta-Analysis, Ingrid Lindquist, Sven R Olson, Ang Li, Hanny Al-Samkari, Janice H Jou, Owen J T Mccarty, Joseph J Shatzel

Faculty, Staff and Students Publications

Thrombopoietin receptor agonists (TPO-RAs) can mitigate preprocedural thrombocytopenia in patients with chronic liver disease (CLD) however their effects on procedural outcomes is unclear. In this meta-analysis, we aimed to better define the efficacy, thrombotic risk and bleeding mitigation associated with the use of preoperative TPO-RAs in patients with CLD. We performed a systematic review and meta-analysis of randomized placebo-controlled clinical trials to assess the use of preprocedural TPO-RAs in patients with CLD, searching MEDLINE, EMBASE and the Cochrane library database. Six publications comprising eight randomized trials (1229 patients; 717 received TPO-RAs, 512 received placebo) and three unique TPO-RAs were retrieved. …


Intrapulmonary Teratoma: A Rare Presentation Of Bronchiectasis, Beren Chandler, Garret Duron, Jason Mcclune, Lindsey Goldberg Jan 2022

Intrapulmonary Teratoma: A Rare Presentation Of Bronchiectasis, Beren Chandler, Garret Duron, Jason Mcclune, Lindsey Goldberg

South Atlantic Division GME Research Day 2022

No abstract provided.


High Risk Newly Diagnosed Multiple Myeloma, Phebe Abraham, Cassie Robertson, Aswin Srinivasan, Murtaza N. Bhuriwala, Shan Guo Jan 2022

High Risk Newly Diagnosed Multiple Myeloma, Phebe Abraham, Cassie Robertson, Aswin Srinivasan, Murtaza N. Bhuriwala, Shan Guo

Gulf Coast Division GME Research Day 2022

No abstract provided.


Not Just An Accident: A Case Of Insulinoma, Asanka Ekanayake, Harrison Stubbs, Dominique Broutin, Olga Karasik, Mustafa Kinaan Jan 2022

Not Just An Accident: A Case Of Insulinoma, Asanka Ekanayake, Harrison Stubbs, Dominique Broutin, Olga Karasik, Mustafa Kinaan

North Florida Division GME Research Day 2022

No abstract available.


Modified Chitosan For Effective Renal Delivery Of Sirna To Treat Acute Kidney Injury., Weimin Tang, Chinmay M. Jogdeo, Sudipta Panja, Siyuan Tang, Ling Ding, Ao Yu, Kirk W. Foster, Del L. Dsouza, Yashpal S. Chhonker, Heather Jensen Smith, Hee-Seong Jang, Erika I. Boesen, Daryl J. Murry, Babu Padanilam, David Oupicky Jan 2022

Modified Chitosan For Effective Renal Delivery Of Sirna To Treat Acute Kidney Injury., Weimin Tang, Chinmay M. Jogdeo, Sudipta Panja, Siyuan Tang, Ling Ding, Ao Yu, Kirk W. Foster, Del L. Dsouza, Yashpal S. Chhonker, Heather Jensen Smith, Hee-Seong Jang, Erika I. Boesen, Daryl J. Murry, Babu Padanilam, David Oupicky

Journal Articles: Eppley Institute

Acute kidney injury (AKI) is characterized by a sudden decrease in renal function and impacts growing number of people worldwide. RNA interference (RNAi) showed potential to treat diseases with no or limited conventional therapies, including AKI. Suitable carriers are needed to protect and selectively deliver RNAi to target cells to fully explore this therapeutic modality. Here, we report on the synthesis of chitosan modified with α-cyclam-p-toluic acid (C-CS) as a novel siRNA carrier for targeted delivery to injured kidneys. We demonstrate that conjugation of the α-cyclam-p-toluic acid to chitosan imparts the C-CS polymer with targeting and antagonistic properties to cells …


Dually Active Polycation/Mirna Nanoparticles For The Treatment Of Fibrosis In Alcohol-Associated Liver Disease, Chuhan Zhang, Yu Hang, Weimin Tang, Diptesh Sil, Heather Jensen Smith, Robert G. Bennett, Benita L. Mcvicker, David Oupicky Jan 2022

Dually Active Polycation/Mirna Nanoparticles For The Treatment Of Fibrosis In Alcohol-Associated Liver Disease, Chuhan Zhang, Yu Hang, Weimin Tang, Diptesh Sil, Heather Jensen Smith, Robert G. Bennett, Benita L. Mcvicker, David Oupicky

Journal Articles: Eppley Institute

Alcohol-associated liver disease (AALD) is a major cause of liver disorders worldwide. Current treatment options are limited, especially for AALD-associated fibrosis. Promising approaches include RNA interference for miR-155 overexpression in Kupffer cells (KCs), as well as the use of CXCR4 antagonists that inhibit the activation of hepatic stellate cells (HSCs) through the CXCL12/CXCR4 axis. The development of dual-functioning nanoparticles for the effective delivery of antifibrotic RNA together with a CXCR4 inhibitor thus promises to improve the treatment of AALD fibrosis. In this study, cholesterol-modified polymeric CXCR4 inhibitor (Chol-PCX) was synthesized and used to encapsulate anti-miR-155 or non-coding (NC) miRNA in …


Machine Learning Analyses Of Highly-Multiplexed Immunofluorescence Identifies Distinct Tumor And Stromal Cell Populations In Primary Pancreatic Tumors, Krysten Vance, Alphan Alitinok, Seth Winfree, Heather Jensen Smith, Benjamin Swanson Md, Phd, Paul M. Grandgenett, Kelsey Klute, Daniel J Crichton, Michael A. Hollingsworth Jan 2022

Machine Learning Analyses Of Highly-Multiplexed Immunofluorescence Identifies Distinct Tumor And Stromal Cell Populations In Primary Pancreatic Tumors, Krysten Vance, Alphan Alitinok, Seth Winfree, Heather Jensen Smith, Benjamin Swanson Md, Phd, Paul M. Grandgenett, Kelsey Klute, Daniel J Crichton, Michael A. Hollingsworth

Journal Articles: Eppley Institute

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a formidable challenge for patients and clinicians.

OBJECTIVE: To analyze the distribution of 31 different markers in tumor and stromal portions of the tumor microenvironment (TME) and identify immune cell populations to better understand how neoplastic, non-malignant structural, and immune cells, diversify the TME and influence PDAC progression.

METHODS: Whole slide imaging (WSI) and cyclic multiplexed-immunofluorescence (MxIF) was used to collect 31 different markers over the course of nine distinctive imaging series of human PDAC samples. Image registration and machine learning algorithms were developed to largely automate an imaging analysis pipeline identifying distinct cell …


Primary Retroperitoneal Mucinous Tumor – A Cyst That Is Not So Simple, Scott Cruise, Aaron Dan Pinnola, Abhishek Srivastava Jan 2022

Primary Retroperitoneal Mucinous Tumor – A Cyst That Is Not So Simple, Scott Cruise, Aaron Dan Pinnola, Abhishek Srivastava

South Atlantic Division GME Research Day 2022

No abstract provided.


Identification Of Lung Cancer Drivers By Comparison Of The Observed And The Expected Numbers Of Missense And Nonsense Mutations In Individual Human Genes, Olga Y Gorlova, Marek Kimmel, Spiridon Tsavachidis, Christopher I Amos, Ivan P Gorlov Jan 2022

Identification Of Lung Cancer Drivers By Comparison Of The Observed And The Expected Numbers Of Missense And Nonsense Mutations In Individual Human Genes, Olga Y Gorlova, Marek Kimmel, Spiridon Tsavachidis, Christopher I Amos, Ivan P Gorlov

Faculty, Staff and Students Publications

Largely, cancer development is driven by acquisition and positive selection of somatic mutations that increase proliferation and survival of tumor cells. As a result, genes related to cancer development tend to have an excess of somatic mutations in them. An excess of missense and/or nonsense mutations in a gene is an indicator of its cancer relevance. To identify genes with an excess of potentially functional missense or nonsense mutations one needs to compare the observed and expected numbers of mutations in the gene. We estimated the expected numbers of missense and nonsense mutations in individual human genes using (i) the …


Loss Of Mmr And Tgfbr2 Increases The Susceptibility To Microbiota-Dependent Inflammation-Associated Colon Cancer, Elena Tosti, Ana S Almeida, Tam T T Tran, Mariel Barbachan E Silva, Pilib Ó Broin, Robert Dubin, Ken Chen, Amanda P Beck, Andrew S Mclellan, Eduardo Vilar, Aaron Golden, Paul W O'Toole, Winfried Edelmann Jan 2022

Loss Of Mmr And Tgfbr2 Increases The Susceptibility To Microbiota-Dependent Inflammation-Associated Colon Cancer, Elena Tosti, Ana S Almeida, Tam T T Tran, Mariel Barbachan E Silva, Pilib Ó Broin, Robert Dubin, Ken Chen, Amanda P Beck, Andrew S Mclellan, Eduardo Vilar, Aaron Golden, Paul W O'Toole, Winfried Edelmann

Faculty, Staff and Student Publications

Background and aims: Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. Therefore, we generated an animal model to study how the loss of both TGFBR2 signaling impacts dMMR-driven intestinal tumorigenesis in vivo and explore the impact of the gut microbiota.

Methods: We generated VCMsh2/Tgfbr2 mice in which Msh2loxP and Tgfbr2loxP alleles are …


Targeting The Pro-Survival Protein Bcl-2 To Prevent Breast Cancer, Adelaide Young, Wen Bu, Weiyu Jiang, Amy Ku, Jyoti Kapali, Sagar Dhamne, Lan Qin, Susan G Hilsenbeck, Yi-Chieh Nancy Du, Yi Li Jan 2022

Targeting The Pro-Survival Protein Bcl-2 To Prevent Breast Cancer, Adelaide Young, Wen Bu, Weiyu Jiang, Amy Ku, Jyoti Kapali, Sagar Dhamne, Lan Qin, Susan G Hilsenbeck, Yi-Chieh Nancy Du, Yi Li

Faculty, Staff and Students Publications

Current chemopreventive strategies require 3-5 years of continuous treatment and have the concerns of significant side effects; therefore, new chemopreventive agents that require shorter and safer treatments are urgently needed. In this study, we developed a new murine model of breast cancer that mimics human breast cancer initiation and is ideal for testing the efficacy of chemopreventive therapeutics. In this model, introduction of lentivirus carrying a PIK3CA gene mutant commonly found in breast cancers infects a small number of the mammary cells, leading to atypia first and then to ductal carcinomas that are positive for both estrogen receptor and progesterone …


An Unusual Case Of Breast Implant-Associated Anaplastic Large Cell Lymphoma, Sarah Premji, Andreia Barbieri, Christine Roth, Eric M Rohren, Gustavo Rivero, Sravanti P Teegavarapu Jan 2022

An Unusual Case Of Breast Implant-Associated Anaplastic Large Cell Lymphoma, Sarah Premji, Andreia Barbieri, Christine Roth, Eric M Rohren, Gustavo Rivero, Sravanti P Teegavarapu

Faculty, Staff and Students Publications

INTRODUCTION: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare disease entity associated with textured breast implants. Though the clinical course is typically indolent, BIA-ALCL can occasionally invade through the capsule into the breast parenchyma with spread to the regional lymph nodes and beyond including chest wall invasive disease.

CASE: We present the case of a 51-year-old female with a history of bilateral silicone breast implants placed approximately twenty years ago who presented with two months of progressively enlarging right breast mass. Ultrasound-guided biopsy of right breast mass and right axillary lymph node showed CD 30-positive

CONCLUSION: Treatment guidelines …


The Transcriptomic Portrait Of Locally Advanced Breast Cancer And Its Prognostic Value In A Multi-Country Cohort Of Latin American Patients, Andrea Sabina Llera, Eliana Saul Furquim Werneck Abdelhay, Nora Artagaveytia, Adrián Daneri-Navarro, Bettina Müller, Carlos Velazquez, Elsa B Alcoba, Isabel Alonso, Daniela B Alves Da Quinta, Renata Binato, Alicia Inés Bravo, Natalia Camejo, Dirce Maria Carraro, Mónica Castro, Juan M Castro-Cervantes, Sandra Cataldi, Alfonso Cayota, Mauricio Cerda, Alicia Colombo, Susanne Crocamo, Alicia Del Toro-Arreola, Raúl Delgadillo-Cisterna, Lucía Delgado, Marisa Dreyer-Breitenbach, Laura Fejerman, Elmer A Fernández, Jorge Fernández, Wanda Fernández, Ramón A Franco-Topete, Carolina Gabay, Fancy Gaete, Adriana Garibay-Escobar, Jorge Gómez, Gonzalo Greif, Thomas G Gross, Marisol Guerrero, Marianne K Henderson, Miguel E Lopez-Muñoz, Alejandra Lopez-Vazquez, Silvina Maldonado, Andrés J Morán-Mendoza, Maria Aparecida Nagai, Antonio Oceguera-Villanueva, Miguel A Ortiz-Martínez, Jael Quintero, Antonio Quintero-Ramos, Rui M Reis, Javier Retamales, Ernesto Rivera-Claisse, Darío Rocha, Robinson Rodríguez, Cristina Rosales, Efrain Salas-González, Verónica Sanchotena, Laura Segovia, Juan Martín Sendoya, Aida A Silva-García, Alejandra Trinchero, Olivia Valenzuela, Vidya Vedham, Livia Zagame, United States-Latin American Cancer Research Network (Us-Lacrn);, Osvaldo L Podhajcer Jan 2022

The Transcriptomic Portrait Of Locally Advanced Breast Cancer And Its Prognostic Value In A Multi-Country Cohort Of Latin American Patients, Andrea Sabina Llera, Eliana Saul Furquim Werneck Abdelhay, Nora Artagaveytia, Adrián Daneri-Navarro, Bettina Müller, Carlos Velazquez, Elsa B Alcoba, Isabel Alonso, Daniela B Alves Da Quinta, Renata Binato, Alicia Inés Bravo, Natalia Camejo, Dirce Maria Carraro, Mónica Castro, Juan M Castro-Cervantes, Sandra Cataldi, Alfonso Cayota, Mauricio Cerda, Alicia Colombo, Susanne Crocamo, Alicia Del Toro-Arreola, Raúl Delgadillo-Cisterna, Lucía Delgado, Marisa Dreyer-Breitenbach, Laura Fejerman, Elmer A Fernández, Jorge Fernández, Wanda Fernández, Ramón A Franco-Topete, Carolina Gabay, Fancy Gaete, Adriana Garibay-Escobar, Jorge Gómez, Gonzalo Greif, Thomas G Gross, Marisol Guerrero, Marianne K Henderson, Miguel E Lopez-Muñoz, Alejandra Lopez-Vazquez, Silvina Maldonado, Andrés J Morán-Mendoza, Maria Aparecida Nagai, Antonio Oceguera-Villanueva, Miguel A Ortiz-Martínez, Jael Quintero, Antonio Quintero-Ramos, Rui M Reis, Javier Retamales, Ernesto Rivera-Claisse, Darío Rocha, Robinson Rodríguez, Cristina Rosales, Efrain Salas-González, Verónica Sanchotena, Laura Segovia, Juan Martín Sendoya, Aida A Silva-García, Alejandra Trinchero, Olivia Valenzuela, Vidya Vedham, Livia Zagame, United States-Latin American Cancer Research Network (Us-Lacrn);, Osvaldo L Podhajcer

Faculty, Staff and Students Publications

PURPOSES: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches.

PATIENTS AND METHODS: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival …


Multi-Antigen-Targeted T-Cell Therapy To Treat Patients With Relapsed/Refractory Breast Cancer, Valentina Hoyos, Spyridoula Vasileiou, Manik Kuvalekar, Ayumi Watanabe, Ifigeneia Tzannou, Yovana Velazquez, Matthew French-Kim, Wingchi Leung, Suhasini Lulla, Catherine Robertson, Claudette Foreman, Tao Wang, Shaun Bulsara, Natalia Lapteva, Bambi Grilley, Matthew Ellis, Charles Kent Osborne, Angela Coscio, Julie Nangia, Helen E Heslop, Cliona M Rooney, Juan F Vera, Premal Lulla, Mothaffar Rimawi, Ann M Leen Jan 2022

Multi-Antigen-Targeted T-Cell Therapy To Treat Patients With Relapsed/Refractory Breast Cancer, Valentina Hoyos, Spyridoula Vasileiou, Manik Kuvalekar, Ayumi Watanabe, Ifigeneia Tzannou, Yovana Velazquez, Matthew French-Kim, Wingchi Leung, Suhasini Lulla, Catherine Robertson, Claudette Foreman, Tao Wang, Shaun Bulsara, Natalia Lapteva, Bambi Grilley, Matthew Ellis, Charles Kent Osborne, Angela Coscio, Julie Nangia, Helen E Heslop, Cliona M Rooney, Juan F Vera, Premal Lulla, Mothaffar Rimawi, Ann M Leen

Faculty, Staff and Students Publications

PURPOSE: Adoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer (BC). In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed antigens, Survivin, NY-ESO-1, MAGE-A4, SSX2, and PRAME, to patients with relapsed/refractory/metastatic BC.

MATERIALS AND METHODS: MultiTAA T-cell products were generated from the peripheral blood of heavily pre-treated patients with metastatic or locally recurrent unresectable BC of all subtypes and infused at a fixed dose level of 2 × 107/m2. Patients received two infusions of cells 4 …


Biomarkers Of Response And Resistance To Palbociclib Plus Letrozole In Patients With Er+/Her2- Breast Cancer, Mitch Dowsett, Lucy Kilburn, Mothaffar F Rimawi, C Kent Osborne, Katherine Pogue-Geile, Yuan Liu, Samuel A Jacobs, Melanie Finnigan, Shannon Puhalla, Andrew Dodson, Vera Martins, Maggie Cheang, Sophie Perry, Chris Holcombe, Nick Turner, Claire Swift, Judith M Bliss, Stephen Johnston Jan 2022

Biomarkers Of Response And Resistance To Palbociclib Plus Letrozole In Patients With Er+/Her2- Breast Cancer, Mitch Dowsett, Lucy Kilburn, Mothaffar F Rimawi, C Kent Osborne, Katherine Pogue-Geile, Yuan Liu, Samuel A Jacobs, Melanie Finnigan, Shannon Puhalla, Andrew Dodson, Vera Martins, Maggie Cheang, Sophie Perry, Chris Holcombe, Nick Turner, Claire Swift, Judith M Bliss, Stephen Johnston

Faculty, Staff and Students Publications

PURPOSE: To determine (i) the relationship between candidate biomarkers of the antiproliferative (Ki67) response to letrozole and palbociclib alone and combined in ER

EXPERIMENTAL DESIGN: 307 postmenopausal women with ER+/HER2− primary breast cancer were randomly assigned to neoadjuvant treatment with letrozole for 14 weeks; letrozole for 2 weeks, then letrozole+palbociclib to 14 weeks; palbociclib for 2 weeks, then letrozole+palbociclib to 14 weeks; or letrozole+palbociclib for 14 weeks. Biopsies were taken at baseline, 2 and 14 weeks and surgery at varying times after stopping palbociclib. Immunohistochemical analyses were conducted for Ki67, c-PARP, ER, PgR, RB1, CCNE1, and CCND1.

RESULTS: Higher baselines …


Metabolic Targeting, Immunotherapy And Radiation In Locally Advanced Non-Small Cell Lung Cancer: Where Do We Go From Here?, Annika Dhawan, Phillip M Pifer, Vlad C Sandulache, Heath D Skinner Jan 2022

Metabolic Targeting, Immunotherapy And Radiation In Locally Advanced Non-Small Cell Lung Cancer: Where Do We Go From Here?, Annika Dhawan, Phillip M Pifer, Vlad C Sandulache, Heath D Skinner

Faculty, Staff and Students Publications

In the US, there are ~250,000 new lung cancer diagnoses and ~130,000 deaths per year, and worldwide there are an estimated 1.6 million deaths per year from this deadly disease. Lung cancer is the most common cause of cancer death worldwide, and it accounts for roughly a quarter of all cancer deaths in the US. Non-small cell lung cancer (NSCLC) represents 80-85% of these cases. Due to an enormous tobacco cessation effort, NSCLC rates in the US are decreasing, and the implementation of lung cancer screening guidelines and other programs have resulted in a higher percentage of patients presenting with …