Medicine and Health Sciences Commons^™

Small Extracellular Vesicle-Mediated Itgb6 Sirna Delivery Downregulates The Αvβ6 Integrin And Inhibits Adhesion And Migration Of Recipient Prostate Cancer Cells, Shiv Ram Krishn, Vaughn Garcia, Nicole M Naranjo, Fabio Quaglia, Christopher D Shields, Maisha A Harris, Andrew V Kossenkov, Qin Liu, Eva Corey, Dario C Altieri, Lucia R Languino

Department of Cancer Biology Faculty Papers

The αVβ6 integrin, an epithelial-specific cell surface receptor absent in normal prostate and expressed during prostate cancer (PrCa) progression, is a therapeutic target in many cancers. Here, we report that transcript levels of ITGB6 (encoding the β6 integrin subunit) are significantly increased in metastatic castrate-resistant androgen receptor-negative prostate tumors compared to androgen receptor-positive prostate tumors. In addition, the αVβ6 integrin protein levels are significantly elevated in androgen receptor-negative PrCa patient derived xenografts (PDXs) compared to androgen receptor-positive PDXs. In vitro, the androgen receptor-negative PrCa cells express high levels of the αVβ6 integrin compared to androgen receptor-positive PrCa cells. Additionally, …

Klrf1, A Novel Marker Of Cd56bright Nk Cells, Predicts Improved Survival For Patients With Locally Advanced Bladder Cancer, Neelam Mukherjee, Niannian Ji, Xi Tan, Chun-Liang Chen, Onika D. V. Noel, Maria Rodriguez-Padron, Chun-Lin Lin, David G. Alonzo, Tim H. Huang, Robert S. Svatek

School of Medicine Publications and Presentations

Background

Bladder tumor-infiltrating CD56bright NK cells are more tumor cytotoxic than their CD56dim counterparts. Identification of NK cell subsets is labor-intensive and has limited utility in the clinical setting. Here, we sought to identify a surrogate marker of bladder CD56bright NK cells and to test its prognostic significance.

Methods

CD56bright and CD56dim NK cells were characterized with the multiparametric flow (n = 20) and mass cytometry (n = 21) in human bladder tumors. Transcriptome data from bladder tumors (n = 351) profiled by The Cancer Genome Atlas (TCGA) were analyzed. The expression levels of individual markers in intratumoral …

The Diagnostic Performance Of Ultrasonography In The Evaluation Of Extrathyroidal Extension In Papillary Thyroid Carcinoma: A Systematic Review And Meta-Analysis, Peter P. Issa, Aaron L. Albuck, Eslam Hossam, Mohammad Hussein, Mohamed Aboueisha, Abdallah S. Attia, Mahmoud Omar, Seif Abdelrahman, Gehad Naser, Robert D.E. Clark, Eman Toraih, Emad Kandil

School of Medicine Faculty Publications

Extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC) is an indication of disease progression and can influence treatment aggressiveness. This meta-analysis assesses the diagnostic accuracy of ultrasonography (US) in detecting ETE. A systematic review and meta-analysis were performed by searching PubMed, Embase, and Cochrane for studies published up to April 2022. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated. The areas under the curve (AUC) for summary receiver operating curves were compared. A total of 11 studies analyzed ETE in 3795 patients with PTC. The sensitivity of ETE detection was 76% (95%CI = 74–78%). The …

Stabilized Core Gene And Pathway Election Uncovers Pan-Cancer Shared Pathways And A Cancer-Specific Driver, Pathum Kossinna, Weijia Cai, Xuewen Lu, Carrie S Shemanko, Qingrun Zhang

Department of Cancer Biology Faculty Papers

Approaches systematically characterizing interactions via transcriptomic data usually follow two systems: (i) coexpression network analyses focusing on correlations between genes and (ii) linear regressions (usually regularized) to select multiple genes jointly. Both suffer from the problem of stability: A slight change of parameterization or dataset could lead to marked alterations of outcomes. Here, we propose Stabilized COre gene and Pathway Election (SCOPE), a tool integrating bootstrapped least absolute shrinkage and selection operator and coexpression analysis, leading to robust outcomes insensitive to variations in data. By applying SCOPE to six cancer expression datasets (BRCA, COAD, KIRC, LUAD, PRAD, and THCA) in …

Antibody Epitope Profiling Of The Kshv Lana Protein Using Virscan, Sydney J. Bennett, Dicle Yalcin, Sara R. Privatt, Owen Ngalamika, Salum J. Lidenge, John T. West, Charles Wood

School of Medicine Faculty Publications

The humoral antibody response against Kaposi sarcoma-associated herpesvirus (KSHV) in infected individuals has been characterized demonstrating the latency-associated nuclear antigen (LANA) as the most antigenic KSHV protein. Despite the antigenicity of the protein, specific LANA epitopes have not been systematically characterized. Here, we utilized a bacteriophage T7 library, which displays 56-amino acid KSHV LANA peptides with 28-amino acid overlap (VirScan), to define those epitopes in LANA targeted by antibodies from a cohort of 62 sub-Saharan African Kaposi Sarcoma (KS) patients and 22 KSHV-infected asymptomatic controls. Intra- and inter-patient breadth and magnitude of the anti-LANA responses were quantified at the peptide …

Adjuvant Nab-Paclitaxel + Gemcitabine In Resected Pancreatic Ductal Adenocarcinoma: Results From A Randomized, Open-Label, Phase Iii Trial, Margaret A. Tempero, Uwe Pelzer, Eileen M. O'Reilly, Jordan Winter, Do-Youn Oh, Chung-Pin Li, Giampaolo Tortora, Heung-Moon Chang, Charles D. Lopez, Tanios Bekaii-Saab, Andrew H. Ko, Armando Santoro, Joon Oh Park, Marcus S. Noel, Giovanni Luca Frassineti, Yan-Shen Shan, Andrew Dean, Hanno Riess, Eric Van Cutsem, Jordan Berlin, Philip Philip, Malcolm Moore, David Goldstein, Josep Tabernero, Mingyu Li, Stefano Ferrara, Yvan Le Bruchec, George Zhang, Brian Lu, Andrew V. Biankin, Michele Reni

Department of Surgery Faculty Papers

PURPOSE

This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430). METHODS

We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS

Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab …

Co-Management Strategies For Acute Myeloid Leukemia Patients In The Community Setting, Christopher Benton, Michael R Grunwald, Hana Safah, Margaret Kasner

Department of Medical Oncology Faculty Papers

The treatment landscape for acute myeloid leukemia (AML) has changed substantially in recent years. The introduction of newer therapies, including oral agents, less myelosuppressive agents, and parenteral regimens suitable for outpatient administration, has made it feasible for select patients to receive therapy in the outpatient setting and in community practices. Thorough patient evaluation (including molecular testing), planned supportive care (eg, transfusion support, antimicrobial prophylaxis), and vigilant patient monitoring (for tumor lysis syndrome and adverse events) by a multidisciplinary team are required for successful management of patients both in the community and at specialized leukemia centers. Some patients are unable or …

Association Of Brafv600e Mutation With The Aggressive Behavior Of Papillary Thyroid Microcarcinoma: A Meta-Analysis Of 33 Studies, Abdallah S. Attia, Mohammad Hussein, Peter P. Issa, Ahmad Elnahla, Ashraf Farhoud, Brandon M. Magazine, Mohanad R. Youssef, Mohamed Aboueisha, Mohamed Shama, Eman Toraih, Emad Kandil

School of Medicine Faculty Publications

An association between the BRAFV600E mutation and the clinicopathological progression of papillary thyroid microcarcinoma (PTMC) has been suggested. We aimed to summarize the relevant literature and determine the predictive value of BRAFV600E mutation in predicting clinical outcomes and risk stratification in patients with PTMC. A systematic search using PubMed, Cochrane, and Embase up to February 2020 was performed. A total of 33 studies met the inclusion criteria, resulting in a pool of 8838 patients, of whom 5043 (57.1%) patients were positive for BRAFV600E mutation. Tumors with positive BRAFV600E mutation had a higher tendency for multifocality (RR = 1.09, 95%CI = …

Notch Signaling Pathway: A Comprehensive Prognostic And Gene Expression Profile Analysis In Breast Cancer, Hassan Yousefi, Afshin Bahramy, Narges Zafari, Mahsa Rostamian Delavar, Khoa Nguyen, Atousa Haghi, Tahmineh Kandelouei, Cecilia Vittori, Parham Jazireian, Sajad Maleki, Danyal Imani, Amin Moshksar, Amirreza Bitaraf, Sadegh Babashah

School of Medicine Faculty Publications

Breast cancer is a complex disease exhibiting a great degree of heterogeneity due to different molecular subtypes. Notch signaling regulates the differentiation of breast epithelial cells during normal development and plays a crucial role in breast cancer progression through the abnormal expression of the Notch up-and down-stream effectors. To date, there are only a few patient-centered clinical studies using datasets characterizing the role of Notch signaling pathway regulators in breast cancer; thus, we investigate the role and functionality of these factors in different subtypes using publicly available databases containing records from large studies. High-throughput genomic data and clinical information extracted …

Detection Of Progression Or Regression Of Breast Cancer By Circulating Tumor Dna (Ctdna), Ujjwal Karki, Bipin Ghimire, Emma Herrman, Siddhartha Yadav, Mohammad Muhsin Chisti

Conference Presentation Abstracts

Circulating tumor DNA (ctDNA) are short DNA sequences shed by tumor cells into the systemic circulation. Studies have shown potential utility of the test to predict relapse or recurrence following treatment in solid tumors, but sensitivity and specificity have varied widely, ranging from 19-100% and 80-100% respectively, in breast cancer specifically. Moreover, literature describing the utility of monitoring dynamic changes in ctDNA trends is limited. We aim to evaluate the correlation between ctDNA test, both single test as well as dynamic trends in value over time, with imaging findings.

Federated Learning Enables Big Data For Rare Cancer Boundary Detection, Sarthak Pati, Ujjwal Baid, Brandon Edwards, Micah Sheller, Shih-Han Wang, G. Anthony Reina, Patrick Foley, Alexey Gruzdev, Deepthi Karkada, Christos Davatzikos, Chiharu Sako, Satyam Ghodasara, Michel Bilello, Suyash Mohan, Philipp Vollmuth, Gianluca Brugnara, Chandrakanth J. Preetha, Felix Sahm, Klaus Maier-Hein, Maximilian Zenk, Martin Bendszus, Wolfgang Wick, Evan Calabrese, Jeffrey Rudie, Javier Villanueva-Meyer, Soonmee Cha, Madhura Ingalhalikar, Manali Jadhav, Umang Pandey, Jitender Saini, John Garrett, Matthew Larson, Robert Jeraj, Stuart Currie, Russell Frood, Kavi Fatania, Raymond Y. Huang, Ken Chang, Carmen Balaña, Jaume Capellades, Josep Puig, Johannes Trenkler, Josef Pichler, Georg Necker, Andreas Haunschmidt, Stephan Meckel, Gaurav Shukla, Spencer Liem, Gregory S Alexander, Joseph Lombardo, Joshua D. Palmer, Adam E. Flanders, Adam P. Dicker, Haris I. Sair, Craig K. Jones, Archana Venkataraman, Meirui Jiang, Tiffany Y. So, Cheng Chen, Pheng Ann Heng, Qi Dou, Michal Kozubek, Filip Lux, Jan Michálek, Petr Matula, Miloš Keřkovský, Tereza Kopřivová, Marek Dostál, Václav Vybíhal, Michael A. Vogelbaum, J. Ross Mitchell, Joaquim Farinhas, Joseph A. Maldjian, Chandan Ganesh Bangalore Yogananda, Marco C. Pinho, Divya Reddy, James Holcomb, Benjamin C. Wagner, Benjamin M. Ellingson, Timothy F. Cloughesy, Catalina Raymond, Talia Oughourlian, Akifumi Hagiwara, Chencai Wang, Minh-Son To, Sargam Bhardwaj, Chee Chong, Marc Agzarian, Alexandre Xavier Falcão, Samuel B. Martins, Bernardo C. A. Teixeira, Flávia Sprenger, David Menotti, Diego R. Lucio, Pamela Lamontagne, Daniel Marcus, Benedikt Wiestler, Florian Kofler, Ivan Ezhov, Marie Metz, Rajan Jain, Matthew Lee, Yvonne W. Lui, Richard Mckinley, Johannes Slotboom, Piotr Radojewski, Raphael Meier, Roland Wiest, Derrick Murcia, Eric Fu, Rourke Haas, John Thompson, David Ryan Ormond, Chaitra Badve, Andrew E. Sloan, Vachan Vadmal, Kristin Waite, Rivka R. Colen, Linmin Pei, Murat Ak, Ashok Srinivasan, J. Rajiv Bapuraj, Arvind Rao, Nicholas Wang, Ota Yoshiaki, Toshio Moritani, Sevcan Turk, Joonsang Lee, Snehal Prabhudesai, Fanny Morón, Jacob Mandel, Konstantinos Kamnitsas, Ben Glocker, Luke V. M. Dixon, Matthew Williams, Peter Zampakis, Vasileios Panagiotopoulos, Panagiotis Tsiganos, Sotiris Alexiou, Ilias Haliassos, Evangelia I Zacharaki, Konstantinos Moustakas, Christina Kalogeropoulou, Dimitrios M. Kardamakis, Yoon Seong Choi, Seung-Koo Lee, Jong Hee Chang, Sung Soo Ahn, Bing Luo, Laila Poisson, Ning Wen, Pallavi Tiwari, Ruchika Verma, Rohan Bareja, Ipsa Yadav, Jonathan Chen, Neeraj Kumar, Marion Smits, Sebastian R. Van Der Voort, Ahmed Alafandi, Fatih Incekara, Maarten M. J. Wijnenga, Georgios Kapsas, Renske Gahrmann, Joost W Schouten, Hendrikus J. Dubbink, Arnaud J. P. E. Vincent, Martin J. Van Den Bent, Pim J. French, Stefan Klein, Yading Yuan, Sonam Sharma, Tzu-Chi Tseng, Saba Adabi, Simone P. Niclou, Olivier Keunen, Ann-Christin Hau, Martin Vallières, David Fortin, Martin Lepage, Bennett Landman, Karthik Ramadass, Kaiwen Xu, Silky Chotai, Lola B. Chambless, Akshitkumar Mistry, Reid C. Thompson, Yuriy Gusev, Krithika Bhuvaneshwar, Anousheh Sayah, Camelia Bencheqroun, Anas Belouali, Subha Madhavan, Thomas C. Booth, Alysha Chelliah, Marc Modat, Haris Shuaib, Carmen Dragos, Aly Abayazeed, Kenneth Kolodziej, Michael Hill, Ahmed Abbassy, Shady Gamal, Mahmoud Mekhaimar, Mohamed Qayati, Mauricio Reyes, Ji Eun Park, Jihye Yun, Ho Sung Kim, Abhishek Mahajan, Mark Muzi, Sean Benson, Regina G. H. Beets-Tan, Jonas Teuwen, Alejandro Herrera-Trujillo, Maria Trujillo, William Escobar, Ana Abello, Jose Bernal, Jhon Gómez, Joseph Choi, Stephen Baek, Yusung Kim, Heba Ismael, Bryan Allen, John M. Buatti, Aikaterini Kotrotsou, Hongwei Li, Tobias Weiss, Michael Weller, Andrea Bink, Bertrand Pouymayou, Hassan F. Shaykh, Joel Saltz, Prateek Prasanna, Sampurna Shrestha, Kartik M. Mani, David Payne, Tahsin Kurc, Enrique Pelaez, Heydy Franco-Maldonado, Francis Loayza, Sebastian Quevedo, Pamela Guevara, Esteban Torche, Cristobal Mendoza, Franco Vera, Elvis Ríos, Eduardo López, Sergio A. Velastin, Godwin Ogbole, Mayowa Soneye, Dotun Oyekunle, Olubunmi Odafe-Oyibotha, Babatunde Osobu, Mustapha Shu'aibu, Adeleye Dorcas, Farouk Dako, Amber L. Simpson, Mohammad Hamghalam, Jacob J. Peoples, Ricky Hu, Anh Tran, Danielle Cutler, Fabio Y. Moraes, Michael A. Boss, James Gimpel, Deepak Kattil Veettil, Kendall Schmidt, Brian Bialecki, Sailaja Marella, Cynthia Price, Lisa Cimino, Charles Apgar, Prashant Shah, Bjoern Menze, Jill S. Barnholtz-Sloan, Jason Martin, Spyridon Bakas

Department of Radiation Oncology Faculty Papers

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically …

Standard Deviations Of Mr Signal Intensities Show A Consistent Trend During Imaging Follow-Ups For Glioblastoma Patients When Corrected For Non-Biological Heterogeneity Due To Hardware And Software Variation, Subhendra N. Sarkar, Rafael Rojas, Evans Lespinasse, Xiang Fu Zhang, Ruth Zeron

Publications and Research

Introduction: Glioblastoma multiforme (GBM) has a poor prognosis in spite of advanced MRI guided treatments today. Routine MRI using conventional T1 or advanced permeability based MRI of GBM often does not adequately represent changing tumor phases or overall survival. In this work, region of interest (ROI) based tissue MR standard deviation (SD) is demonstrated as an important MRI variable that could be a potential biomarker of GBM heterogeneity and radioresistance. Materials and methods: MRI characterization is often qualitative and lacks reproducibility. Using standardized MRI phantoms we have normalized retrospective records of 12 radioresistant GBM patients that underwent radiation therapy (RT) …

Idiopathic Pulmonary Fibrosis And Lung Cancer: Future Directions And Challenges, Ahmad Abu Qubo, Jamil Numan, Juan Snijder, Maria Padilla, John H.M. Austin, Kathleen M. Capaccione, Monica Pernia, Jean Bustamante, Timothy O’Connor, Mary M. Salvatore

Einstein Health Papers

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of pulmonary scarring. New treatments slow disease progression and allow pulmonary fibrosis patients to live longer. Persistent pulmonary fibrosis increases a patient’s risk of developing lung cancer. Lung cancer in patients with IPF differs from cancers that develop in the non-fibrotic lung. Peripherally located adenocarcinoma is the most frequent cell type in smokers who develop lung cancer, while squamous cell carcinoma is the most frequent in pulmonary fibrosis. Increased fibroblast foci in IPF are associated with more aggressive cancer behaviour and shorter doubling times. Treatment of lung cancer in fibrosis is challenging …

A Single Centre Experience Of Local Perforator Flaps In Oncoplastic Breast Surgery: A Cross-Sectional Study, Sana Zeeshan, Lubna Vohra, Uzma Shamsi, Nida Zahid, Danish Ali, Nargis Asad, Cristina Garusi

Section of General Surgery

Background & objectives: Various oncoplastic techniques have emerged over the years to preserve breast cosmesis and symmetry without compromising the principles of tumor excision. One of the newer techniques for breast volume replacement to achieve symmetry and cosmesis is the use of fasciocutaneous pedicled chest wall perforator flaps or local perforator flaps (LPF). The objectives of this study were to document the details of the surgical procedure as well as patient-reported satisfaction and well-being following the procedure using a validated BREAST-Q tool among Pakistani women.
Materials & methods: This cross-sectional study was conducted from March 2019 to February 2021 enrolling …

Does Mainstream Brca Testing Affect Surgical Decision-Making In Newly-Diagnosed Breast Cancer Patients?, Quratul Ain, Caroline Richardson, Miriam Mutebi, Angela George, Zoe Kemp, Jennifer E. Rusby

General Surgery, East Africa

Background: Germline pathogenic variants mutations) in the BRCA1 and BRCA2 genes cause an increased risk of breast cancer and ovarian cancer. Mainstream cancer genetic testing (MCG) was introduced for breast cancer patients in our unit in 2013. Non-geneticist clinicians have been trained to offer genetic testing during initial treatment planning. We assessed the impact of timely test results on surgical decision-making.

Methods: Women who had undergone mainstream genetic testing for breast cancer between September 2013 and September 2018 were identified from a prospective database. Surgical data were collected retrospectively.

Results: 580 eligible women had mainstream genetic testing. …

Anticancer Effect Of Illicium Verum (Star Anise Fruit) Against Human Breast Cancer Mcf-7 Cell Line, Asra Khan Pahore, Shagufta Khan, Nasim Karim

Department of Biological & Biomedical Sciences

Objective: To investigate the anticancer effect of Illicium verum against human breast cancer MCF-7 cell line.
Methods: An experimental study was conducted in Multidisciplinary and Tissue Culture Laboratory, Aga Khan University in collaboration with Pharmacology Department of Bahria University Medical and Dental College, Karachi, Pakistan from January 2021 to June 2021. MCF-7 cells of Luminal-A breast cancer were seeded in 96-well plate and treated with I.verum methanol extract. After incubation, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) dye was used for cell viability and cell proliferation assays to determine the number of dead and viable cells, and the absorbance was measured using an enzyme-linked …

High Local Control And Low Ocular Toxicity Using Ultra-Low-Dose “Boom-Boom” Radiotherapy For Indolent Orbital Lymphoma, Sanjna Shelukar, Christian Fernandez, Zeynep Bas, Lydia Komarnicky, Sara E. Lally, Carol L Shields, Adam Binder, Pierluigi Porcu, Onder Alpdogan, Ubaldo Martinez-Outschoorn, Wenyin Shi

Department of Medical Oncology Faculty Papers

Background: The first line definitive treatment for early-stage indolent B-cell lymphoma is radiation therapy (RT). Due to the sensitivity of orbital structures to radiation, ultra-low-dose RT (4 Gy in 2 fractions, "boom-boom") has and been utilized as an attractive option for orbital lymphoma. In this retrospective study, we evaluated the outcome and toxicity of "boom-boom" RT for indolent orbital lymphoma with an emphasis on ophthalmologic toxicity.

Methods: This is a retrospective case series with 17 patients with orbital lymphoma who received boom-boom RT at a single tertiary referral center between January 2017 and June 2022. Medical records, imaging and radiation …

Efficacy And Safety Of Lifileucel, A One-Time Autologous Tumor-Infiltrating Lymphocyte (Til) Cell Therapy, In Patients With Advanced Melanoma After Progression On Immune Checkpoint Inhibitors And Targeted Therapies: Pooled Analysis Of Consecutive Cohorts Of The C-144-01 Study, Jason Chesney, Karl D Lewis, Harriet Kluger, Omid Hamid, Eric Whitman, Sajeve Thomas, Martin Wermke, Mike Cusnir, Evidio Domingo-Musibay, Giao Q Phan, John M Kirkwood, Jessica C Hassel, Marlana Orloff, James Larkin, Jeffrey Weber, Andrew J S Furness, Nikhil I Khushalani, Theresa Medina, Michael E Egger, Friedrich Graf Finckenstein, Madan Jagasia, Parameswaran Hari, Giri Sulur, Wen Shi, Xiao Wu, Amod Sarnaik

Department of Medical Oncology Faculty Papers

Background: Patients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed after ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2 cell therapy trial in melanoma.

Methods: Eligible patients had advanced melanoma that progressed after ICI and targeted therapy, where appropriate. Melanoma lesions were resected (resected tumor diameter ≥1.5 cm) and shipped to a central good manufacturing …

A National Multi-Institutional Analysis Of Predictors Of Surgical Site Complications And Unplanned Reoperation After Paramedian Forehead Flap Reconstruction, Garrett Ni, Rohan Brebion, Pablo A. Baltodano, Michael C. Coronado, Nicholas Elmer, Theresa K. Webster, Huaqing Zhao, Xiaoning Lu, Sthefano Araya, Sameer Patel

Student Papers, Posters & Projects

Background: Although postoperative complications of paramedian forehead flap (PMFF) are generally low, surgical site complications and unplanned reoperation can still occur. Recent literature suggests infection to be the most common complication following PMFF reconstruction. This study sought to determine the patient and preoperative factors associated with surgical site complications and unplanned reoperations at a national level.

Methods: Patients who underwent PMFF reconstruction from the ACS-NSQIP 2007 - 2019 database were analyzed to determine composite surgical site morbidity and unplanned return to the operating room. Patient and operative factors were also analyzed to assess independent risk factors for surgical site morbidity …

Il-1Β Enhances Cell Viability And Decreases 5-Fu Sensitivity In Novel Colon Cancer Cell Lines Derived From African American Patients, Marzia Spagnardi, Jenny Paredes, Jovanny Zabaleta, Jone Garai, Tiana Reyes, Laura A. Martello, Jennie L. Williams

School of Medicine Faculty Publications

Background: In the U.S., African Americans (AAs) present with the highest incidence and mortality rates for Colorectal Cancer (CRC). When compared to Caucasian American (CA) patients, AAs also have reduced response to the first line standard of care chemotherapeutic agent 5-Fluorouracil (5-FU). Previously, we observed differential gene expression between the two populations, suggesting that colon tumors from AA patients display a decreased antitumor immune response and an increased expression of genes encoding proteins involved in inflammatory processes, such as Interleukin-1β (IL-1β). Here, we investigate the role of IL-1β in modifying chemotherapeutic response and altering expression of proteins in novel AA …

Characterizing Pulmonary Function Test Changes For Patients With Lung Cancer Treated On A 2-Institution, 4-Dimensional Computed Tomography-Ventilation Functional Avoidance Prospective Clinical Trial, Ryan C. Miller, Richard Castillo, Edward Castillo, Bernard L Jones, Moyed Miften, Brian Kavanagh, Bo Lu, Maria Werner-Wasik, Nader Ghassemi, Joseph Lombardo, Julie Barta, Inga Grills, Chad G Rusthoven, Thomas Guerrero, Yevgeniy Vinogradskiy

Department of Radiation Oncology Faculty Papers

Purpose: Four-dimensional computed tomography (4DCT)-ventilation-based functional avoidance uses 4DCT images to generate plans that avoid functional regions of the lung with the goal of reducing pulmonary toxic effects. A phase 2, multicenter, prospective study was completed to evaluate 4DCT-ventilation functional avoidance radiation therapy. The purpose of this study was to report the results for pretreatment to posttreatment pulmonary function test (PFT) changes for patients treated with functional avoidance radiation therapy.

Methods and materials: Patients with locally advanced lung cancer receiving chemoradiation were accrued. Functional avoidance plans based on 4DCT-ventilation images were generated. PFTs were obtained at baseline and 3 months …

Expansion Of The Detrusor Muscular Ring Surrounding The Bladder Neck On Mri: Moving Beyond The Prostate As An Etiology Of Lower Urinary Tract Symptoms Due To Benign Prostatic Hyperplasia, Kiran Nandalur, David Walker, Hong Ye, Sayf A. Al-Katib, Brian Seifman, David Gangwish, Abhay Dhaliwal, Connor Ervin, Kayla Dobies, Channing Sesoko, Sirisha Nandalur, Bernadette Zwaans, Jennifer Nguyen, Jason Hafron

Conference Presentation Abstracts

Purpose: The etiology of lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH) remains uncertain. The purpose of our study was to quantitatively analyze pelvic anatomic characteristics on magnetic resonance imaging (MRI) to assess for independent factors for symptoms.
*Methods and Materials: This retrospective single-institution study evaluated treatment-naïve men who underwent prostate MRI within 3 months of International Prostate Symptom Score (IPSS) from June 2021 to February 2022. Factors measured on MRI included: detrusor muscular ring surrounding the bladder neck measured as area and alternatively diameter, central gland (CG) mean apparent diffusion coefficient (ADC), levator hiatus (LH) volume, intrapelvic …

Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir Uddin

Department of Pathology and Laboratory Medicine

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal …

Epigenetic Regulation In Chromium-, Nickel- And Cadmium-Induced Carcinogenesis, Lei Zhao, Ranakul Islam, Yifang Wang, Xiujuan Zhang, Ling-Zhi Liu

Department of Medical Oncology Faculty Papers

Environmental and occupational exposure to heavy metals, such as hexavalent chromium, nickel, and cadmium, are major health concerns worldwide. Some heavy metals are well-documented human carcinogens. Multiple mechanisms, including DNA damage, dysregulated gene expression, and aberrant cancer-related signaling, have been shown to contribute to metal-induced carcinogenesis. However, the molecular mechanisms accounting for heavy metal-induced carcinogenesis and angiogenesis are still not fully understood. In recent years, an increasing number of studies have indicated that in addition to genotoxicity and genetic mutations, epigenetic mechanisms play critical roles in metal-induced cancers. Epigenetics refers to the reversible modification of genomes without changing DNA sequences; …

Clinical Impact Of Number Of Lymph Nodes Dissected On Postoperative Survival In Node-Negative Small Cell Lung Cancer, Shinkichi Takamori, Takefumi Komiya Md, Emily Powell Phd

PCI Publications and Projects

Objectives: Small cell lung cancer (SCLC) is a lethal histologic subtype of lung cancer. Although the Commission on Cancer recommends pathological examination of at least 10 lymph nodes dissected (LNDs) for resected early-stage non-small cell lung cancer, its survival benefit of LNDs in patients with early-stage SCLC is unknown.

Methods: The National Cancer Database was queried for SCLC patients with clinical stage I-II and clinical N0, NX disease per AJCC 7th edition who had undergone lobectomy between 2004 and 2017. Overall survival of SCLC patients by the number of LNDs was compared using Log-rank tests. Univariate and multivariable Cox proportional …

New Insights Into Avian Infectious Bronchitis Virus In Colombia From Whole-Genome Analysis, Gloria Ramirez-Nieto, Daiana Mir, Diego Almansa-Villa, Geovanna Cordoba-Argotti, Magda Beltran-Leon, Nelida Rodriguez-Osorio, Jone Garai, Jovanny Zabaleta, Arlen P. Gomez

School of Medicine Faculty Publications

Infectious Bronchitis (IB) is a respiratory disease caused by a highly variable Gammacoronavirus, which generates a negative impact on poultry health worldwide. GI-11 and GI-16 lineages have been identified in South America based on Infectious Bronchitis virus (IBV) partial S1 sequences. However, full genome sequence information is limited. In this study we report, for the first time, the whole-genome sequence of IBV from Colombia. Seven IBV isolates obtained during 2012 and 2013 from farms with respiratory disease compatible with IB were selected and the complete genome sequence was obtained by NGS. According to S1 sequence phylogenetic analysis, six isolates belong …

Reducing Liver Cancer Risk Through Dietary Change: Positive Results From A Community-Based Educational Initiative In Three Racial/Ethnic Groups, Lin Zhu, Ellen Jaeson Kim, Evelyn González, Marilyn A. Fraser, Steven Zhu, Nathaly Rubio-Torio, Grace X. Ma, Ming-Chin Yeh, Yin Tan

Publications and Research

Dietary behaviors and alcohol consumption have been linked to liver disease and liver cancer. So far, most of the liver cancer awareness campaigns and behavioral interventions have focused on preventive behaviors such as screening and vaccination uptake, while few incorporated dietary aspects of liver cancer prevention. We implemented a community-based education initiative for liver cancer prevention among the African, Asian, and Hispanic populations within the Greater Philadelphia and metropolitan New York City areas. Data from the baseline and the 6-month follow-up surveys were used for the assessment of changes in dietary behaviors and alcohol consumption among participants. In total, we …

Response To Chen Et. Al, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Whilst our paper was published in three parts to assist with readability it is essentially a single report. Our analysis moves logically from continuous and categorical bivariate studies to inverse probability weighted multivariate (IPWM) and then geospatiotemporal analysis and finally statistical analysis of geospatiotemporal models. Context is important. As stated by Chen and colleagues IPWM models are very powerful and present compelling conclusions and have the effect of transforming ecological into pseudo-randomized studies from which it is entirely proper to draw causal conclusions. That this report follows similar earlier IPWM and geotemporospatial reports on the commonest cancer in adults and …

Is There A Role For Allogeneic Hematopoietic Stem Cell Transplantation For Refractory Follicular Lymphoma?, Yang Yang, Xia Bi, Mia Gergis, Usama Gergis

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

No abstract provided.

Simultaneous Onset Of Haematological Malignancy And Covid: An Epicovideha Survey, Chiara Cattaneo, Jon Salmanton-García, Francesco Marchesi, Shaimaa El-Ashwah, Federico Itri, Barbora Weinbergerová, Maria Gomes Da Silva, Michelina Dargenio, Julio Dávila-Valls, Natasha Ali

Department of Pathology and Laboratory Medicine

Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines.
Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022.
Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients …