Medical Specialties Commons^™

Management Of Patients With Brain Metastases From Non-Small Cell Lung Cancer And Adverse Prognostic Features: Multi-National Radiation Treatment Recommendations Are Heterogeneous, Minesh Mehta

All Publications

No abstract provided.

Li-Rads: A Conceptual And Historical Review From Its Beginning To Its Recent Integration Into Aasld Clinical Practice Guidance, Khaled M. Elsayes, Ania Z. Kielar, Victoria Chernyak, Ali Morshid, Alessandro Furlan, William R. Masch, Robert M. Marks, Aya Kamaya, Richard K. G. Do, Yuko Kono, Kathryn J. Fowler, An Tang, Mustafa R. Bashir, Elizabeth M. Hecht, Kedar Jambhekar, Andrej Lyshchik, Shuchi K. Rodgers, Jay P. Heiken, Marc Kohli, David T. Fetzer, Stephanie R. Wilson, Zahra Kassam, Mishal Mendiratta-Lala, Amit G. Singal, Christopher S. Lim, Irene Cruite, James Lee, Ryan Ash, Donald G. Mitchell, Matthew D. F. Mcinnes

Radiology Faculty Publications

The Liver Imaging Reporting and Data System (LI-RADS^®) is a comprehensive system for standardizing the terminology, technique, interpretation, reporting, and data collection of liver observations in individuals at high risk for hepatocellular carcinoma (HCC). LI-RADS is supported and endorsed by the American College of Radiology (ACR). Upon its initial release in 2011, LI-RADS applied only to liver observations identified at CT or MRI. It has since been refined and expanded over multiple updates to now also address ultrasound-based surveillance, contrast-enhanced ultrasound for HCC diagnosis, and CT/MRI for assessing treatment response after locoregional therapy. The LI-RADS 2018 version was …

Pilot Study For Using Fitbit Activity Trackers To Monitor And Predict Onset Of Car-T Cell Immunotherapy Related Adverse Events Including Cytokine Release Syndrome, Cassra Clark, Ms, Bs, Adam Dicker, Md, Phd, Fastro, Margaret Kasner, Md, Msce, Gina Keiffer, Md, Neil Palmisiano, Md, Ms, Pierluigi Porcu, Md, Kaitlin Rancani, Crnp, Vincent Yeung, Md, Lindsay Wilde, Md

Phase 1

Introduction: Immunotherapy using T Cells with engineered chimeric antigen receptors (CAR) is a revolutionary modality for treating cancer, especially B cell malignancies. It also has specific toxicities. The most common toxicities observed are cytokine-release syndrome (CRS) and neurotoxicity. These therapy-related adverse events can range from mild to fatal. If appropriately and timely treated, they have a good prognosis. Thus, further insight into predictive biomarkers can help clinical management of patients and reduce morbidity and mortality.

Objective: One of the constitutional symptoms associated with CRS is fatigue. With the advent of activity tracking digital technology, I propose a pilot study exploring …

Identifying The Causes Of Cancer Readmissions: A Patient Centered Approach, Emily Wei, Katie Holland, Allison Zibelli, Md

Phase 1

Introduction: Readmission rates of cancer patients remain high, while the rates of many other conditions are decreasing in the United States. Cancer patients are a plurality of patients readmitted to hospitals within 30 days of discharge, and have a high rate of avoidable readmission. Therefore, it is important to understand why these readmissions happen in order to prevent their occurrence.

Objective: This study hopes to identify specific, and potentially personal, reasons that bring cancer patients back to the hospital. Patient perspective may reveal trends that are not apparent in medical record chart reviews. This information can present an opportunity to …

Factors Associated With Stage At Presentation Among Patients With Rare Pancreatic Tumors: An Exploratory Analysis Of The Seer Database, J. Subramoney, D. Delgado, V. Nguyen, R. Denneny, B. George, E. Mitchell, Md

Phase 1

Introduction: Rare pancreatic carcinomas (PC) account for roughly 15% of all pancreatic cancers and approximately 8,300 new cases within the US annually. Little research compares initial stage at diagnosis among rare vs. common pancreatic tumors. The aim of this study was to examine associations between tumor histology and initial stage at diagnosis among cases of rare pancreatic cancers.

Methods: Retrospective cohort study, using the NCI’s Surveillance, Epidemiology, and End Results (SEER) 1990-2015 database. We included patients diagnosed with pancreatic cancer aged 18+. Histology was classified into four categories (ductal, carcinoid, mucinous adenocarcinoma, and undetermined) and stage was dichotomized …

Management Of Retinoblastoma In Older Children (>5 Years) Using Intra-Arterial Chemotherapy: Comparison Of Outcomes To Pre-Chemotherapy And Intravenous Chemotherapy Eras, Evan Selzer, Ms, R. Joel Welch, Md, Pascal Jabbour, Md, Ann Leahey, Md, Carol L. Shields, Md

Phase 1

Introduction: Intra-arterial chemotherapy (IAC) has emerged as an effective treatment for retinoblastoma (RB), but little information exists regarding its use in older patients (>5 years). We evaluate the use of IAC (2008-2018) for RB in older patients and compare outcomes to those in the pre-chemotherapy (<1994) and intravenous chemotherapy (IVC) (1994-2007) eras.

Objective: To evaluate the hypothesis that IAC is effective in managing RB in older patients.

Methods: We performed a retrospective analysis of all patients older than 5 years who were treated with IAC for RB from 2008-2018 on the Ocular Oncology Service at the Wills Eye Hospital. Comparisons were made to historic, …

Identifying Refractory Aml Patients Using Rate Of Wbc Decline In Order To Reduce Length Of Stay, Kyle Itri, Thomas Klumpp

Phase 1

Introduction: Acute Myeloid Leukemia (AML) is the most common acute leukemia in the United States. At diagnosis, these patients are admitted to begin induction chemotherapy and remain in the hospital throughout treatment. Response to therapy is assessed with bone marrow biopsy one month later. However, rate of white blood cell (WBC) and absolute blast count (ABC) decline can be useful in predicting bone marrow blast clearance and complete remission.

Objective: Therefore, our goal is to identify AML patients refractory to induction therapy using rate of WBC, ABC, and ANC decline as prognostic markers in order to reduce length of stay. …

Racial Disparities In Head And Neck Cancers In An Urban Hospital, Jessica Kraus-Lavy, Charnita Zeigler-Johnson, Scott W Keith, Frances Guiles, David Cognetti, Voichita Bar-Ad, Rita S. Axelrod, Md

Phase 1

Introduction: Head and neck cancer incidence rates are higher for white residents in Philadelphia, while related mortality rates are highest for black residents. It is unclear how risk factors like HPV and smoking contribute to these disparities. The goal of this study is to determine which factors are associated with head and neck cancers in a diverse patient population from a Philadelphia hospital.

Methods: Cancer registry data from Thomas Jefferson University was used to obtain records from 922 head and neck cancer patients. One patient of other race was excluded. Twenty in-situ cancer cases were excluded. Chi-square tests were used …

Retrospective Chart Review Assessing Factors That Contribute To Network Leakage In Postoperative Pancreatic Cancer Patients, Nazanin Sarpoulaki, Christian Fernandez, Md, Mark Hurwitz, Md

Phase 1

Introduction: Standard of care for resectable pancreatic cancer includes surgery, chemotherapy, with consideration of radiotherapy. Thomas Jefferson University Hospital (TJUH) is a large volume institution for pancreatectomy. Rate of subsequent in-network adjuvant treatment are far less which may impact outcomes. We will elucidate variables that influence coordinated patient care.

Objective: To evaluate variables that correlate with follow up and adjuvant treatment of pancreatic cancer patients at TJUH.

Methods: Retrospective medical chart reviews will be performed with data from patients with pancreatic cancer who have undergone resection at TJUH from April 2017 to March 2018. Patient demographics, clinical, and pathologic information …

High Density Of Tumor-Associated Macrophage Staining Correlates With Poor Clinicopathologic Markers In Head And Neck Squamous Cell Carcinoma: A Meta-Analysis, Alexander Knops, Ba, Ayan Kumar, Bs, Brian Swendseid, Md, Ubaldo E. Martinez-Outshoorn, Md, Larry Harshyne, Phd, Nancy Philp, Phd, Ulrich Rodeck, Md, Phd, Christopher Snyder, Adam Luginbuhl, Md, David Cognetti, Md, Jennifer Johnson, Md, Joseph Curry, Md

Phase 1

Background: Head and neck squamous cell carcinoma (HNSCC) develops within a complex cellular microenvironment that promotes tumor growth, but also represents many potential therapeutic targets. Macrophage presence within that environment has been implicated in the growth, aggression, and persistence of HNSCC. Current literature reports variable degrees of association between tumor-associated macrophage (TAMs) density and clinicopathologic markers of disease.Inconsistent findings may result from grouping of TAM subtypes, which include both M1 (pro-inflammatory) and M2 (immunosuppressive). Our aim is to define the prognostic significance of the phenotypes of tumor-associated macrophages in HNSCC.

Methods: We conducted a meta-analysis of the existing publications investigating …

Sociodemographic Background Characteristics Of Patients Who Participate In A Lung Cancer Screening Program, Amber Zhang, Marcella Pimpinelli, Brooke Ruane, Russell K. Mcintire, Julie Barta, Md, Hee-Soon Juon, Bridget Jackson

Phase 1

Introduction: Despite decreasing lung cancer incidence and mortality rates, disparities in prevalence and outcomes persist between Black and White patients. Secondary analysis of the National Lung Screening Trial found screening with low-dose CT (LDCT) reduced lung cancer mortality more in Blacks than Whites. However, it is unknown if racial disparities exist in screening results, and the involved sociodemographic factors.

Objective: The study aims to analyze characteristics that may predict screening outcomes (Lung-RADS category) in patients who received LDCT through the Jefferson Lung Cancer Screening Program (LCSP).

Methods: Retrospective data (n=733, May 2015 to July 2017) were merged with prospective …

Clinical And Pathologic Factors In Breast Cancer Patients With Bone Metastases Undergoing Surgery For Pathologic And Impending Fractures, Emily Bochner, Kerith Wang, Benjamin Leiby, Ayako Miura, William Kevin Kelly

Phase 1

Introduction: Metastatic lesions to bone carry a poor prognosis. Bone lesions can be responsible for significant morbidity in patients, including pathologic or impending fractures that may require emergent surgical evaluation.

Objective: We evaluated the clinical and pathologic features associated with breast cancer patients with bone metastases who underwent surgery for pathologic or impending fractures.

Methods: A retrospective chart review of 20 breast cancer patients with bone metastases who underwent surgery from the Bone Biorepository Bank at Sidney Kimmel Cancer Center was performed. We evaluated their clinical and pathologic characteristics and performed Fisher’s Exact Testing to explore potential associations.

Results: 90% …

Identifying The Causes Of Cancer Readmissions: A Patient Centered Approach, Katie Holland, Emily Wei, Allison Zibelli

Phase 1

While there are large efforts to decrease readmission rates in the United States, cancer patients represent a population that has been overlooked. Cancer patients are a vulnerable population who make up a large portion of hospital readmissions. Most of the current research on the causes of readmissions in cancer patients focuses on medical chart reviews and insurance claims. Many of these studies fail to incorporate patient input which could further the understanding of the complete burden associated with cancer readmissions. The goal of this study is to understand the personal reasons behind the decision of cancer patients to return to …

Oral Cancer Awareness Among University Students From Karachi, Pakistan, Dnyanesh Limaye, Patrick Ziesenis, Vaidehi Limaye, Mansoor Ahmad, Farah Saeed, Mahboob Alam, Ramla Rizvi, Atul Kapadi, Sushama Sathe, Gerhard Fortwengel

Section of Dental-Oral Maxillofacial Surgery

Background: Oral cancers (OC) are malignant lesions occurring in the oral cavity that include squamous cell carcinomas (SCC), salivary gland and odontogenic neoplasms. Even though it is the eighth most common malignancy globally but in Pakistan it is the second commonest type of cancer. Lack of awareness about ill-effects of preventable risk factors of oral cancer increases the burden of disease due to the associated high cost of treatment, permanent impairment and high mortality. Hence, awareness can be very helpful in prevention, control and early diagnosis of oral cancer.
Methods: A cross-sectional study was carried out among university students from …

The Pathway To Low Outlier Status In Venous Thromboembolism Events: An Analysis Of Pancreatic Surgery In Acs Nsqip, Samantha L. Savitch, Tyler M. Bauer, Nikosi H. Alvarez, Adam P. Johnson, Theresa P. Yeo, Harish Lavu, Charles J. Yeo, Jordan M. Winter, Geno J. Merli, Scott W. Cowan

Phase 1

Introduction: Our institution’s hepatopancreaticobiliary service (HPBS) is a high-volume pancreatic surgery service, which has demonstrated consistently low rates of symptomatic venous thromboembolism (VTE) compared to similar institutions as reported by NSQIP. We sought to determine if the HPBS’s regimented multimodal VTE prophylaxis pathway plays a role in achieving consistently low VTE rates.

Methods: We queried the ACS NSQIP Participant User File and our institution’s data from 2011-2016 for major pancreatic operations. We used Chi-squared analysis to compare the HPBS and national patient populations, and created a matched dataset based on preoperative patient factors. Univariate and multivariate analyses were performed on …

Phase 1 Dose-Escalation Study Of Momelotinib, A Janus Kinase 1/2 Inhibitor, Combined With Gemcitabine And Nab-Paclitaxel In Patients With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma., Kimmie Ng, Andrew Hendifar, Alexander Starodub Md, Jorge Chaves, Yingsi Yang, Brian Koh, David Barbie, William C Hahn, Charles S Fuchs

PCI Publications and Projects

Purpose Preclinical evidence suggests the importance of Janus activating kinase (JAK) and TANK-binding kinase 1 (TBK1) in pancreatic ductal adenocarcinoma (PDAC). We evaluated the safety and efficacy of momelotinib (MMB), a JAK1/2 inhibitor with additional activity against TBK1, plus albumin-bound paclitaxel + gemcitabine (nab-P + G), in patients with previously untreated metastatic PDAC. Experimental Design Patients were enrolled into five cohorts of increasing doses of MMB between 100 and 200 mg administered once or twice daily in combination with nab-P + G in 28-day cycles to determine maximum tolerated dose (MTD). Safety, efficacy, pharmacokinetics, and pharmacodynamics were assessed for all …

A Nomogram To Determine Required Seed Air Kerma Strength In Planar 131 Cesium Permanent Seed Implant Brachytherapy, Emily Hubley, Michael Trager, Voichita Bar-Ad, Adam J. Luginbuhl, Laura Doyle

Department of Radiation Oncology Faculty Papers

Purpose: Intraoperatively implanted Cesium-131 ( ¹³¹ Cs) permanent seed brachytherapy is used to deliver highly localized re-irradiation in recurrent head and neck cancers. A single planar implant of uniform air kerma strength (AKS) seeds and 10 mm seed-to-seed spacing is used to deliver the prescribed dose to a point 5 mm or 10 mm perpendicular to the center of the implant plane. Nomogram tables to quickly determine the required AKS for rectangular and irregularly shaped implants were created and dosimetrically verified. By eliminating the need for a full treatment planning system plan, nomogram tables allow for fast dose calculation for …

Radiomics - Using Artificial Intelligence In The Quest Towards Personalised Radiation Treatment, Ahmed Nadeem Abbasi, Agha Muhammad Hammad Khan, Bilal Mazhar Qureshi

Department of Radiation Oncology

No abstract provided.

Immediate Versus Delayed Exercise In Men Initiating Androgen Deprivation: Effects On Bone Density And Soft Tissue Composition, Dennis R. Taaffe, Daniel A. Galvao, Nigel Spry, David Joseph, Suzanne K. Chambers, Robert A. Gardiner, Dickon Hayne, Prue Cormie, David H.K. Shum, Robert U. Newton

Research outputs 2014 to 2021

OBJECTIVES: To examine whether it is more efficacious to commence exercise medicine in men with prostate cancer at the onset of androgen-deprivation therapy (ADT) rather than later on during treatment to preserve bone and soft-tissue composition, as ADT results in adverse effects including: reduced bone mineral density (BMD), loss of muscle mass, and increased fat mass (FM).

PATIENTS AND METHODS: In all, 104 patients with prostate cancer, aged 48-84 years initiating ADT, were randomised to immediate exercise (IMEX, n = 54) or delayed exercise (DEL, n = 50) conditions. The former consisted of 6 months of supervised resistance/aerobic/impact exercise and …

Quality Of Life And Psychological Distress In Cancer Survivors: The Role Of Psycho-Social Resources For Resilience, Craig A. Harms, Lynne Cohen, Julie Ann Pooley, Suzanne K. Chambers, Daniel A. Galvao, Robert U. Newton

Research outputs 2014 to 2021

OBJECTIVE: To examine the association between scores on the Protective Factors for Resilience Scale (PFRS) (as a measure of a person's psycho-social resources for resilience) and quality of life as well as symptoms of psychological distress for adult cancer survivors.

METHODS: In this cross-sectional study, 295 cancer survivors (59% female) provided background demographic information and completed the PFRS as well as measures of quality of life and psychological distress previously validated with cancer survivors. Most of the survivors were diagnosed with breast or prostate cancer.

RESULTS: Analysis of the data confirmed the factor structure for the PFRS …

Mitf Has A Central Role In Regulating Starvation-Induced Autophagy In Melanoma., Katrin Möller, Sara Sigurbjornsdottir, Asgeir O Arnthorsson, Vivian Pogenberg, Ramile Dilshat, Valerie Fock, Solveig H Brynjolfsdottir, Christian Bindesboll, Margret Bessadottir, Helga M Ogmundsdottir, Anne Simonsen, Lionel Larue, Matthias Wilmanns, Vesteinn Thorsson, Eirikur Steingrimsson, Margret H Ogmundsdottir

Articles, Abstracts, and Reports

The MITF transcription factor is a master regulator of melanocyte development and a critical factor in melanomagenesis. The related transcription factors TFEB and TFE3 regulate lysosomal activity and autophagy processes known to be important in melanoma. Here we show that MITF binds the CLEAR-box element in the promoters of lysosomal and autophagosomal genes in melanocytes and melanoma cells. The crystal structure of MITF bound to the CLEAR-box reveals how the palindromic nature of this motif induces symmetric MITF homodimer binding. In metastatic melanoma tumors and cell lines, MITF positively correlates with the expression of lysosomal and autophagosomal genes, which, interestingly, …

Bilateral Acute Ocular Ischemic Syndrome Following Head And Neck Radiation, Dipali Nemade, Paul Ferguson, Vikram Shivkumar, Dennis Cole

Marshall Journal of Medicine

Previous literature has established a clear correlation between radiation therapy (RT) to the head and neck leading to aggressive atherosclerosis of the carotid arteries and subsequent increased risk for ischemic stroke. Stenosis of carotid arteries can lead to Ocular Ischemic syndrome (OIS). We present a case of acute bilateral OIS following head and neck RT for left tonsillar squamous cell carcinoma (SCC) in a 64 year-old Caucasian male. Routine large vessel cerebrovascular screening following head and neck radiotherapy should be considered as a means of potentially mitigating future stroke risk through initiation of medical therapy and interventional modalities as a …

Cytisine-Linked Isoflavonoid Antineoplastic Agents For The Treatment Of Cancer, Chunming Liu, David S. Watt, Mykhaylo S. Frasinyuk, Vitaliy M. Sviripa, Wen Zhang, Svitlana P. Bondarenko

Markey Cancer Center Faculty Patents

Cytisine-linked isoflavonoids, or pharmaceutically acceptable salts thereof or pharmaceutically acceptable compositions thereof, are useful for the treatment of conditions in which cells have a reliance on peroxisomal HSD17B4 to degrade very long chain fatty acids and provide necessary energy for cell proliferation, such as is seen in colorectal cancer and prostate cancer, for example.

Coordinating An Oncology Precision Medicine Clinic Within An Integrated Health System: Lessons Learned In Year One, Michael A. Thompson, Jennifer J. Godden, Deborah Wham, Antony Ruggeri, Michael P. Mullane, Amanda Wilson, Shamsuddin Virani, Scott M. Weissman, Brenda Ramczyk, Pamela Vanderwall, James L. Weese

Journal of Patient-Centered Research and Reviews

Precision medicine is a term describing strategies to promote health and prevent and treat disease based on an individual’s genetic, molecular, and lifestyle characteristics. Oncology precision medicine (OPM) is a cancer treatment approach targeting cancer-specific genetic and molecular alterations. Implementation of an OPM clinical program optimally involves the support and collaboration of multiple departments, including administration, medical oncology, pathology, interventional radiology, genetics, research, and informatics. In this review, we briefly introduce the published evidence regarding OPM’s potential effect on patient outcomes and discuss what we have learned over the first year of operating an OPM program within an integrated health …

Shared Heritability And Functional Enrichment Across Six Solid Cancers., Xia Jiang, Hilary K Finucane, Fredrick R Schumacher, Stephanie L Schmit, Jonathan P Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline B Kuchenbaecker, Joe Dennis, David V Conti, Graham Casey, Mia M Gaudet, Jeroen R Huyghe, Demetrius Albanes, Melinda C Aldrich, Angeline S Andrew, Irene L Andrulis, Hoda Anton-Culver, Antonis C Antoniou, Natalia N Antonenkova, Susanne M Arnold, Kristan J Aronson, Banu K Arun, Elisa V Bandera, Rosa B Barkardottir, Daniel R Barnes, Jyotsna Batra, Matthias W Beckmann, Javier Benitez, Sara Benlloch, Andrew Berchuck, Sonja I Berndt, Heike Bickeböller, Stephanie A Bien, Carl Blomqvist, Stefania Boccia, Natalia V Bogdanova, Stig E Bojesen, Manjeet K Bolla, Hiltrud Brauch, Hermann Brenner, James D Brenton, Mark N Brook, Joan Brunet, Hans Brunnström, Daniel D Buchanan, Barbara Burwinkel, Ralf Butzow, Gabriella Cadoni, Trinidad Caldés, Maria A Caligo, Ian Campbell, Peter T Campbell, Géraldine Cancel-Tassin, Lisa Cannon-Albright, Daniele Campa, Neil Caporaso, André L Carvalho, Andrew T Chan, Jenny Chang-Claude, Stephen J Chanock, Chu Chen, David C Christiani, Kathleen B M Claes, Frank Claessens, Judith Clements, J Margriet Collée, Marcia Cruz Correa, Fergus J Couch, Angela Cox, Julie M Cunningham, Cezary Cybulski, Kamila Czene, Mary B Daly, Anna Defazio, Peter Devilee, Orland Diez, Manuela Gago-Dominguez, Jenny L Donovan, Thilo Dörk, Eric J Duell, Alison M Dunning, Miriam Dwek, Diana M Eccles, Christopher K Edlund, Digna R Velez Edwards, Carolina Ellberg, D Gareth Evans, Peter A Fasching, Robert L Ferris, Triantafillos Liloglou, Jane C Figueiredo, Olivia Fletcher, Renée T Fortner, Florentia Fostira, Silvia Franceschi, Eitan Friedman, Steven J Gallinger, Patricia A Ganz, Judy Garber, José A García-Sáenz, Simon A Gayther, Graham G Giles, Andrew K Godwin, Mark S Goldberg, David E Goldgar, Ellen L Goode, Marc T Goodman, Gary E Goodman, Kjell Grankvist, Mark H Greene, Henrik Gronberg, Jacek Gronwald, Pascal Guénel, Niclas Håkansson, Per Hall, Ute Hamann, Freddie C Hamdy, Robert J Hamilton, Jochen Hampe, Aage Haugen, Florian Heitz, Rolando Herrero, Peter Hillemanns, Michael Hoffmeister, Estrid Høgdall, Yun-Chul Hong, John L Hopper, Richard Houlston, Peter J Hulick, David J Hunter, David G Huntsman, Gregory Idos, Evgeny N Imyanitov, Sue Ann Ingles, Claudine Isaacs, Anna Jakubowska, Paul James, Mark A Jenkins, Mattias Johansson, Mikael Johansson, Esther M John, Amit D Joshi, Radka Kaneva, Beth Y Karlan, Linda E Kelemen, Tabea Kühl, Kay-Tee Khaw, Elza Khusnutdinova, Adam S Kibel, Lambertus A Kiemeney, Jeri Kim, Susanne K Kjaer, Julia A Knight, Manolis Kogevinas, Zsofia Kote-Jarai, Stella Koutros, Vessela N Kristensen, Jolanta Kupryjanczyk, Martin Lacko, Stephan Lam, Diether Lambrechts, Maria Teresa Landi, Philip Lazarus, Nhu D Le, Eunjung Lee, Flavio Lejbkowicz, Heinz-Josef Lenz, Goska Leslie, Davor Lessel, Jenny Lester, Douglas A Levine, Li Li, Christopher I Li, Annika Lindblom, Noralane M Lindor, Geoffrey Liu, Fotios Loupakis, Jan Lubiński, Lovise Maehle, Christiane Maier, Arto Mannermaa, Loic Le Marchand, Sara Margolin, Taymaa May, Lesley Mcguffog, Alfons Meindl, Pooja Middha, Austin Miller, Roger L Milne, Robert J Macinnis, Francesmary Modugno, Marco Montagna, Victor Moreno, Kirsten B Moysich, Lorelei Mucci, Kenneth Muir, Anna Marie Mulligan, Katherine L Nathanson, David E Neal, Andrew R Ness, Susan L Neuhausen, Heli Nevanlinna, Polly A Newcomb, Lisa F Newcomb, Finn Cilius Nielsen, Liene Nikitina-Zake, Børge G Nordestgaard, Robert L Nussbaum, Kenneth Offit, Edith Olah, Ali Amin Al Olama, Olufunmilayo I Olopade, Andrew F Olshan, Håkan Olsson, Ana Osorio, Hardev Pandha, Jong Y Park, Nora Pashayan, Michael T Parsons, Tanja Pejovic, Kathryn L Penney, Wilbert H M Peters, Catherine M Phelan, Amanda I Phipps, Dijana Plaseska-Karanfilska, Miranda Pring, Darya Prokofyeva, Paolo Radice, Kari Stefansson, Susan J Ramus, Leon Raskin, Gad Rennert, Hedy S Rennert, Elizabeth J Van Rensburg, Marjorie J Riggan, Harvey A Risch, Angela Risch, Monique J Roobol, Barry S Rosenstein, Mary Anne Rossing, Kim De Ruyck, Emmanouil Saloustros, Dale P Sandler, Elinor J Sawyer, Matthew B Schabath, Johanna Schleutker, Marjanka K Schmidt, V Wendy Setiawan, Hongbing Shen, Erin M Siegel, Weiva Sieh, Christian F Singer, Martha L Slattery, Karina Dalsgaard Sorensen, Melissa C Southey, Amanda B Spurdle, Janet L Stanford, Victoria L Stevens, Sebastian Stintzing, Jennifer Stone, Karin Sundfeldt, Rebecca Sutphen, Anthony J Swerdlow, Eloiza H Tajara, Catherine M Tangen, Adonina Tardon, Jack A Taylor, M Dawn Teare, Manuel R Teixeira, Mary Beth Terry, Kathryn L Terry, Stephen N Thibodeau, Mads Thomassen, Line Bjørge, Marc Tischkowitz, Amanda E Toland, Diana Torres, Paul A Townsend, Ruth C Travis, Nadine Tung, Shelley S Tworoger, Cornelia M Ulrich, Nawaid Usmani, Celine M Vachon, Els Van Nieuwenhuysen, Ana Vega, Miguel Elías Aguado-Barrera, Qin Wang, Penelope M Webb, Clarice R Weinberg, Stephanie Weinstein, Mark C Weissler, Jeffrey N Weitzel, Catharine M L West, Emily White, Alice S Whittemore, H-Erich Wichmann, Fredrik Wiklund, Robert Winqvist, Alicja Wolk, Penella Woll, Michael Woods, Anna H Wu, Xifeng Wu, Drakoulis Yannoukakos, Wei Zheng, Shanbeh Zienolddiny, Argyrios Ziogas, Kristin K Zorn, Jacqueline M Lane, Richa Saxena, Duncan Thomas, Rayjean J Hung, Brenda Diergaarde, James Mckay, Ulrike Peters, Li Hsu, Montserrat García-Closas, Rosalind A Eeles, Georgia Chenevix-Trench, Paul J Brennan, Christopher A Haiman, Jacques Simard, Douglas F Easton, Stephen B Gruber, Paul D P Pharoah, Alkes L Price, Bogdan Pasaniuc, Christopher I Amos, Peter Kraft, Sara Lindström

Articles, Abstracts, and Reports

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r

Itch Nuclear Translocation And H1.2 Polyubiquitination Negatively Regulate The Dna Damage Response, Lufen Chang, Lei Shen, Hu Zhou, Jing Gao, Hangyi Pan, Li Zheng, Brian Armstrong, Yang Peng, Guang Peng, Binhua P. Zhou, Steven T. Rosen, Binghui Shen

Molecular and Cellular Biochemistry Faculty Publications

The downregulation of the DNA damage response (DDR) enables aggressive tumors to achieve uncontrolled proliferation against replication stress, but the mechanisms underlying this process in tumors are relatively complex. Here, we demonstrate a mechanism through which a distinct E3 ubiquitin ligase, ITCH, modulates DDR machinery in triple-negative breast cancer (TNBC). We found that expression of a nuclear form of ITCH was significantly increased in human TNBC cell lines and tumor specimens. Phosphorylation of ITCH at Ser257 by AKT led to the nuclear localization of ITCH and ubiquitination of H1.2. The ITCH-mediated polyubiquitination of H1.2 suppressed RNF8/RNF168-dependent formation of 53BP1 foci, …

Different Genetic Mechanisms Mediate Spontaneous Versus Uvr-Induced Malignant Melanoma, Blake Ferguson, Herlina Y. Handoko, Pamela Mukhopadhyay, Arash Chitsazan, Lois Balmer, Grant Morahan, Graeme J. Walker

Research outputs 2014 to 2021

Genetic variation conferring resistance and susceptibility to carcinogen-induced tumorigenesis is frequently studied in mice. We have now turned this idea to melanoma using the collaborative cross (CC), a resource of mouse strains designed to discover genes for complex diseases. We studied melanoma-prone transgenic progeny across seventy CC genetic backgrounds. We mapped a strong quantitative trait locus for rapid onset spontaneous melanoma onset to Prkdc, a gene involved in detection and repair of DNA damage. In contrast, rapid onset UVR-induced melanoma was linked to the ribosomal subunit gene Rrp15. Ribosome biogenesis was upregulated in skin shortly after UVR exposure. …

Shared Heritability And Functional Enrichment Across Six Solid Cancers, Xia Jiang, Hilary K. Finucane, Fredrick R. Schumacher, Stephanie L. Schmit, Jonathan P. Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline B. Kuchenbaecker, Joe Dennis, David V. Conti, Graham Casey, Mia M. Gaudet, Jeroen R. Huyghe, Demetrius Albanes, Melinda C. Aldrich, Angeline S. Andrew, Irene L. Andrulis, Hoda Anton-Culver, Antonis C. Antoniou, Natalia N. Antonenkova, Susanne M. Arnold, Kristan J. Aronson, Banu K. Arun, Elisa V. Bandera, Rosa B. Barkardottir, Daniel R. Barnes, Jyotsna Batra, Matthias W. Beckmann, Javier Benitez

Markey Cancer Center Faculty Publications

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r_g = 0.57, p = 4.6 × 10⁻⁸), breast and ovarian cancer (r_g = 0.24, p = 7 × 10^{−5 …}

Quality Assurance Guidelines For Interstitial Hyperthermia., H. Dobšíček Trefná, M. Schmidt, G. C. Van Rhoon, H. P. Kok, S. S. Gordeyev, U. Lamprecht, D. Marder, J. Nadobny, P. Ghadjar, S Abdel-Rahman, A. M. Kukiełka, V. Strnad, M. D. Hurwitz, Z. Vujaskovic, C. J. Diederich, P. R. Stauffer, J. Crezee

Department of Radiation Oncology Faculty Papers

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical hyperthermia treatments and trials. This document outlines the clinical and technical consequences of the specific properties of interstitial heat delivery and specifies recommendations for hyperthermia administration with interstitial techniques. Interstitial hyperthermia aims at tumor temperatures in the 40-44 °C range as an adjunct to radiation or chemotherapy. The clinical part of this document imparts specific clinical experience of interstitial heat delivery to various tumor sites as well as recommended interstitial hyperthermia workflow and procedures. The second part describes technical requirements for quality assurance of current interstitial heating equipment …

Microrna-4719 And Microrna-6756-5p Correlate With Castration-Resistant Prostate Cancer Progression Through Interleukin-24 Regulation, Dibash K. Das, Leah Persaud, Moira Sauane

Publications and Research

Prostate cancer (PCa) is the second leading cause of cancer death in the United States. The five-year survival rate for men diagnosed with localized PCa is nearly 100%, yet for those diagnosed with aggressive PCa, it is less than 30%. The pleiotropic cytokine Interleukin-24 (IL-24) has been shown to specifically kill PCa cells compared to normal cells when overexpressed in both in vitro and in vivo studies. Despite this, the mechanisms regulating IL-24 in PCa are not well understood. Since specific microRNAs (miRNAs) are dysregulated in PCa, we used miRNA target prediction algorithm tools to identify miR-4719 and miR-6556-5p as …