Diseases Commons^™

Identifying The Optimal Deep Learning Architecture And Parameters For Automatic Beam Aperture Definition In 3d Radiotherapy, Skylar S Gay, Kelly D Kisling, Brian M Anderson, Lifei Zhang, Dong Joo Rhee, Callistus Nguyen, Tucker Netherton, Jinzhong Yang, Kristy Brock, Anuja Jhingran, Hannah Simonds, Ann Klopp, Beth M Beadle, Laurence E Court, Carlos E Cardenas

Faculty, Staff and Student Publications

PURPOSE: Two-dimensional radiotherapy is often used to treat cervical cancer in low- and middle-income countries, but treatment planning can be challenging and time-consuming. Neural networks offer the potential to greatly decrease planning time through automation, but the impact of the wide range of hyperparameters to be set during training on model accuracy has not been exhaustively investigated. In the current study, we evaluated the effect of several convolutional neural network architectures and hyperparameters on 2D radiotherapy treatment field delineation.

METHODS: Six commonly used deep learning architectures were trained to delineate four-field box apertures on digitally reconstructed radiographs for cervical cancer …

Risk Stratification Model For Hepatocellular Cancer In Patients With Cirrhosis, Fasiha Kanwal, Saira Khaderi, Amit G Singal, Jorge A Marrero, Sumeet K Asrani, Christopher I Amos, Aaron P Thrift, Jennifer R Kramer, Xian Yu, Yumei Cao, Michelle Luster, Abeer Al-Sarraj, Jing Ning, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification index in U.S. cohorts of patients with cirrhosis.

METHODS: We used data from 2 prospective U.S. cohorts to develop the risk index. Patients with cirrhosis were enrolled from 8 centers and followed until development of HCC, death, or December 31, 2021. We identified an optimal set of predictors with the highest discriminatory ability (C-index) for HCC. The predictors were refit using competing risk regression and its predictive performance was evaluated using the area under the receiver-operating …

Low-Dose Aspirin For Primary Prevention Of Cardiovascular Events Comparing East Asians With Westerners: A Meta-Analysis, Rock Bum Kim, Ang Li, Ki-Soo Park, Yune-Sik Kang, Jang-Rak Kim, Eliano P Navarese, Diana A Gorog, Udaya S Tantry, Paul A Gurbel, Jin Yong Hwang, Oh-Young Kwon, Young-Hoon Jeong

Faculty, Staff and Students Publications

BACKGROUND: East Asians have shown different risk profiles for both thrombophilia and bleeding than Western counterparts.

OBJECTIVES: The authors sought to evaluate the effect of low-dose aspirin for primary prevention between these populations.

METHODS: We searched randomized clinical trials (RCTs) for intervention with low-dose aspirin (≤100 mg once daily) in participants without symptomatic cardiovascular disease until December 31, 2021. The number of events between the arms was extracted for analysis. Pooled risk ratios (RRs) and risk differences (RDs) were analyzed in each population. Outcomes included a major adverse cardiovascular event (MACE), cardiovascular death, myocardial infarction, stroke, and major bleeding (intracranial …

Recurrent Oropharyngeal Squamous Cell Carcinomas Maintain Anti-Tumor Immunity And Multinucleation Levels Following Completion Of Radiation, Patricia Castro, Germán Corredor, Can Koyuncu, Luke A Nordstrom, Michelle Tiji, Taylor Leavitt, James S Lewis, Anant Madabhushi, Mitchell J Frederick, Vlad C Sandulache

Faculty, Staff and Students Publications

OBJECTIVE: Oropharyngeal squamous cell carcinoma (OPSCC) recurrence is almost universally fatal. Development of effective therapeutic options requires an improved understanding of recurrent OPSCC biology.

METHODS: We analyzed paired primary-recurrent OPSCC from Veterans treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who received curative intent radiation-based treatment (with or without chemotherapy). Patient tumors were analyzed using standard immunohistochemistry and automated imaging of infiltrating lymphocytes and multinucleated tumor cells coupled to machine learning algorithms.

RESULTS: Primary and recurrent tumors demonstrated high concordance via p16 and p53 immunohistochemistry, with comparable levels of multinucleation. In contrast, recurrent tumors …

Colocolic Fistula: A Rare Consequential Presentation Of Cecal Mucinous Adenocarcinoma, Jessica Rutyna, Paige Stratton, Rutwik Pradeep Sharma, Anthony V. Baratta Jr

Advances in Clinical Medical Research and Healthcare Delivery

Colorectal cancer (CRC) is the second most common cause of cancer death in the United States. Relative to a 5-year survival rate, CRC patients diagnosed with localized disease accrue a 90% survival rate while those diagnosed with distant-stage disease maintain 14% survival. Mucinous adenocarcinoma (MAC) is a unique subtype of CRC characterized by the presence of extracellular mucin occupying 50% of tumor expansion. Fistula complications of colonic malignancy have rarely been reported and more commonly occur as complications of diverticulitis. Colocolic fistulae are atypical consequences of colon cancer, which have been rarely reported. We wish to report a unique case …

Metastatic Breast Cancer Found During Colon Cancer Screening, Rutwik Pradeep Sharma, Tausif Syed, Meenal Sharma, Jay Bapaye, Ahmed Shehadah, Alexander T. Kusnik, Ali Jaan, Richard Alweis, Andrej Strapko

Advances in Clinical Medical Research and Healthcare Delivery

No abstract provided.

Educational Case: An Invasive Salivary Gland Tumor: Adenoid Cystic Carcinoma Of The Parotid Gland, Jaime Eberle-Singh, Madalina Tuluc, Joanna Sue Yee Chan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Incidental Detection Of Fgfr3 Fusion Via Liquid Biopsy Leading To Earlier Diagnosis Of Urothelial Carcinoma, Quillan Huang, Irene Mitsiades, Heidi Dowst, Neda Zarrin-Khameh, Attiya Batool Noor, Patricia Castro, Michael E Scheurer, Guilherme Godoy, Martha P Mims, Nicholas Mitsiades

Faculty, Staff and Students Publications

The rising utilization of circulating tumor DNA (ctDNA) assays in Precision Oncology may incidentally detect genetic material from secondary sources. It is important that such findings are recognized and properly leveraged for both diagnosis and monitoring of response to treatment. Here, we report a patient in whom serial cell-free DNA (cfDNA) monitoring for his known prostate adenocarcinoma uncovered the emergence of an unexpected FGFR3-TACC3 gene fusion, a BRCA1 frameshift mutation, and other molecular abnormalities. Due to the rarity of FGFR3 fusions in prostate cancer, a workup for a second primary cancer was performed, leading to the diagnosis of an otherwise-asymptomatic …

Factors Associated With Thrombo-Hemorrhagic Deaths In Patients With Acute Promyelocytic Leukemia Treated With Arsenic Trioxide And All-Trans Retinoic Acid, C. Singh, U. Yanamandra, P. Karunakaran, N. Jindal, S. Kumar, N. Saini, A. Jandial, A. Jain, D. Lad, G. Prakash, A. Khadwal, S. Naseem, Narender Kumar, J. Ahluwalia, N. Varma, S. Varma, P. Malhotra

School of Medicine Faculty Publications

ISTH 2023 Congress, June 24 - 28, 2023, Montreal, Canada

Discovery, Structure-Activity Relationship And In Vitro Anticancer Activity Of Small-Molecule Inhibitors Of The Protein-Protein Interactions Between Af9/Enl And Af4 Or Dot1l, Xin Li, Xiaowei Wu, Shenyou Nie, Jidong Zhao, Yuan Yao, Fangrui Wu, Chandra Bhushan Mishra, Md Ashraf-Uz-Zaman, Bala Krishna Moku, Yongcheng Song

Faculty, Staff and Students Publications

Simple Summary

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene generate potent fusion oncogenes and cause acute myeloid leukemia or lymphocytic leukemia, which account for ~75% infant and 5–10% child/adult acute leukemia cases with a poor prognosis (5-year survival rates < 45%). Protein–protein interactions between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are critical to malignant gene expression and are therefore a potential drug target for cancer. Compound screening followed by medicinal chemistry studies identified several novel small-molecule inhibitors showing strong inhibition of these protein–protein interactions, significant suppression of characteristic gene expression, and robust cellular anticancer activities with negligible cytotoxicity. These compounds are useful chemical probes for biological studies of these protein–protein interactions, as well as pharmacological leads for further drug development against MLL-rearranged and other leukemias.

Abstract

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene cause 5–10% acute leukemias with poor clinical outcomes. Protein–protein interactions (PPI) between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Several benzothiophene-carboxamide compounds were identified as novel inhibitors of these PPIs with IC₅₀ values as …

Direct Cohort: An Ncorp Longitudinal Observational Trial For Disparities In Results Of Immune Checkpoint Inhibitor Treatment Between Black And White Cancer Patients, Song Yao, Christine B. Ambrosone, Lori Sakoda, Igor Puzanovci, Eva Culakova, Michelle Janelsins, Warren Davis, Thaer Khoury, Elisa Rodriguez, Shipra Gandhi, Allison Magnuson, Guilherme Cantuaria, Jennifer M. Suga, Rajasree P. Chowdry, Lawrence H. Kushi, Karen Mustian, Gary R. Morrow, Charles Kamen

School of Medicine Faculty Publications

38th Annual Meeting of the Society for Immunotherapy of Cancer's, SITC 2023, November 1 -5, 2023, San Diego, CA

Rare De Novo Gain-Of-Function Missense Variants In Dot1l Are Associated With Developmental Delay And Congenital Anomalies, Zelha Nil, Ashish R Deshwar, Yan Huang, Scott Barish, Xi Zhang, Sanaa Choufani, Polona Le Quesne Stabej, Ian Hayes, Patrick Yap, Chad Haldeman-Englert, Carolyn Wilson, Trine Prescott, Kristian Tveten, Arve Vøllo, Devon Haynes, Patricia G Wheeler, Jessica Zon, Cheryl Cytrynbaum, Rebekah Jobling, Moira Blyth, Siddharth Banka, Alexandra Afenjar, Cyril Mignot, Florence Robin-Renaldo, Boris Keren, Oguz Kanca, Xiao Mao, Daniel J Wegner, Kathleen Sisco, Marwan Shinawi, Undiagnosed Disease Network, Michael F Wangler, Rosanna Weksberg, Shinya Yamamoto, Gregory Costain, Hugo J Bellen

Faculty, Staff and Students Publications

Misregulation of histone lysine methylation is associated with several human cancers and with human developmental disorders. DOT1L is an evolutionarily conserved gene encoding a lysine methyltransferase (KMT) that methylates histone 3 lysine-79 (H3K79) and was not previously associated with a Mendelian disease in OMIM. We have identified nine unrelated individuals with seven different de novo heterozygous missense variants in DOT1L through the Undiagnosed Disease Network (UDN), the SickKids Complex Care genomics project, and GeneMatcher. All probands had some degree of global developmental delay/intellectual disability, and most had one or more major congenital anomalies. To assess the pathogenicity of the DOT1L …

The Silence Of Mitotic Figures, Hope K. Haefner Md

Patient Experience Journal

A career in medicine is guided by the patients you treat and those who have taught you to treat these individuals. Communication is of utmost importance in all aspects of healthcare. However, there are times when communication can be difficult. This story takes you through a physician’s experience that led to a career in women’s healthcare, reflecting on the silence that prevailed as her journey began.

Experience Framework

This article is associated with the Staff & Provider Engagement lens of The Beryl Institute Experience Framework (https://theberylinstitute.org/experience-framework/).

• Access other PXJ articles related to this lens.
• Access other resources related …

Impact On The Volume Of Pathology Reports Before And During The Covid-19 Pandemic In Seer Cancer Registries, Amina Chtourou, Pamela V. Sanchez, Todd Golden, Huann Sheng Chen, Stephen M. Schwartz, Xiao Cheng Wu, Brenda Y. Hernandez, Jovanka N. Harrison, Lynne Penberthy, Serban Negoita

School of Public Health Faculty Publications

Introduction: Health care procedures including cancer screening and diagnosis were interrupted due to the COVID-19 pandemic. The extent of this impact on cancer care in the United States is not fully understood. We investigated pathology report volume as a reflection of trends in oncology services pre-pandemic and during the pandemic. Methods: Electronic pathology reports were obtained from 11 U.S. central cancer registries from NCI’s SEER Program. The reports were sorted by cancer site and document type using a validated algorithm. Joinpoint regression was used to model temporal trends from January 2018 to February 2020, project expected counts from March 2020 …

Ewing's Sarcoma Of The Hand: An Unusual Presentation In A Young Hispanic Male, Dylan B Mcbee, Hope A Bentley, Giancarlo Toledanes

Faculty, Staff and Students Publications

Ewing's sarcoma is a neuroectodermal malignancy classically associated with innocuous and chronic symptomatology. Although tumors typically involve the axial skeleton, some malignancies may be confined to extraosseous tissue only. This report presents the case of a 15-year-old Hispanic male with a tender, slow-growing mass of seven months in the subcutaneous tissue of the right hand. Core needle biopsy and fine needle aspiration confirmed the diagnosis of high-grade extraosseous Ewing's sarcoma and the patient was treated via surgical resection and chemotherapy. Nonspecific findings of Ewing's sarcoma may mimic infection or trauma and contribute to a delay in diagnosis. However, social and …

Multidimensional Biomarker Predicts Disease Control In Response To Immunotherapy In Recurrent Or Metastatic Head And Neck Squamous-Cell Carcinoma, Kevin C Flanagan, Jon Earls, Ian Schillebeeckx, Jeffrey Hiken, Rachel L Wellinghoff, Natalie A Lafranzo, Zachary S Bradley, Joey Babbitt, William H Westra, Raymond Hsu, Lincoln Nadauld, Howard Mcleod, Sean D Firth, Brittany Sharp, Josh Fuller, Vera Vavinskaya, Leisa Sutton, Ida Deichaite, Samuel D Bailey, Vlad C Sandulache, Matthew J Rendo, Orlan K Macdonald, Karim Welaya, James L Wade, Andrew W Pippas, Jennifer Slim, Bruce Bank, Steven J Saccaro, Xingwei Sui, Adil Akhtar, Savitha Balaraman, Steven E Kossman, Scott A Sonnier, Todd D Shenkenberg, Warren L Alexander, Katherine A Price, Charles L Bane, Jessica Ley, David N Messina, Jarret I Glasscock, Ezra E W Cohen, Douglas R Adkins, Eric J Duncavage

Faculty, Staff and Students Publications

PURPOSE: Anti-PD-1 therapy provides clinical benefit in 40-50% of patients with relapsed and/or metastatic head and neck squamous cell carcinoma (RM-HNSCC). Selection of anti- PD-1 therapy is typically based on patient PD-L1 immunohistochemistry (IHC) which has low specificity for predicting disease control. Therefore, there is a critical need for a clinical biomarker that will predict clinical benefit to anti-PD-1 treatment with high specificity.

METHODS: Clinical treatment and outcomes data for 103 RM-HNSCC patients were paired with RNA-sequencing data from formalin-fixed patient samples. Using logistic regression methods, we developed a novel biomarker classifier based on expression patterns in the tumor immune …

Prospective Clinical And Biomarker Validation Of The American Society For Transplantation And Cellular Therapy Consensus Definition For Transplantation-Associated Thrombotic Microangiopathy, Shengling Ma, Saleh Bhar, Danielle Guffey, Rock Bum Kim, Mahrukh Jamil, Christopher I Amos, Stephanie J Lee, Sangeeta R Hingorani, Sarah E Sartain, Ang Li

Faculty, Staff and Students Publications

Transplantation-associated thrombotic microangiography (TA-TMA) is a disorder that causes severe complications after allogeneic hematopoietic cell transplantation (allo-HCT). Diagnosing TA-TMA is challenging because of the lack of standardized criteria. In this study, we aimed to evaluate the new TA-TMA consensus definition from the American Society for Transplantation and Cellular Therapy (ASTCT) panel as part of an ongoing prospective pediatric cohort study, and also to compare the impact and outcomes of using the current definition of clinical TMA (cTMA) versus the new consensus definition. We included patients age 0 to 18 years who underwent their first allo-HCT between May 2021 and January …

Screening For Lung Cancer: 2023 Guideline Update From The American Cancer Society, Andrew M. D. Wolf, Kevin C. Oeffinger, Tina Ya-Chen Shih, Louise C. Walter, Timothy R. Church, Elizabeth T. H. Fontham, Elena B. Elkin, Ruth D. Etzioni, Carmen E. Guerra, Rebecca B. Perkins, Karli K. Kondo, Tyler B. Kratzer, Deanna Manassaram-Baptiste, William L. Dahut, Robert A. Smith

School of Public Health Faculty Publications

Lung cancer is the leading cause of mortality and person-years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS …

Identification And Initial Validation Of Maximal Tumor Area As A Novel Prognostic Factor For Overall And Disease-Free Survival In Patients With Resectable Colon Cancer: A Retrospective Study, Fei-Long Ning, Wan-Jie Gu, Lin-Zheng Dai, Wan-Ying Du, Yong-Ji Zeng, Jia-Kui Zhang, Masanobu Abe, Yan-Long Liu, Rui Zhang, Chun-Dong Zhang

Faculty, Staff and Students Publications

BACKGROUND: The tumor area may be a potential prognostic indicator. The present study aimed to determine and validate the prognostic value of tumor area in curable colon cancer.

METHODS: This retrospective study included a training and validation cohorts of patients who underwent radical surgery for colon cancer. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were identified using Cox proportional hazards regression models. The prognostic discrimination was evaluated using the integrated area under the receiver operating characteristic curves (iAUCs) for prognostic factors and models. The prognostic discrimination between tumor area and other individual factors was compared, along …

Comparison Of Progression-Free Survival Outcome Of Sentinel Node Biopsy Without Ultrastaging Versus Lymphadenectomy In Endometrial Cancer: A Propensity-Matched Analysis, Dahye Lee, Yoo-Na Kim, Sang Hyun Cho, Hye Soo Yoon, Young Tae Kim, Sunghoon Kim, Sang Wun Kim

Faculty, Staff and Student Publications

OBJECTIVE: We aimed to investigate the oncologic outcomes of patients with endometrial cancer who underwent sentinel lymph node (SLN) biopsy without ultrastaging compared with that of those who underwent lymphadenectomy (LND).

METHODS: Patients with endometrial cancer who underwent staging with SLN biopsy or LND during 2006 - 2021 were analyzed using propensity score matching (PSM). SLN metastasis was examined using hematoxylin and eosin staining, without ultrastaging. Progression-free survival (PFS) was compared between the two groups before and after PSM using age, histology, and stage as covariates. Clinical variables such as recurrence patterns and lymphatic complications, were assessed.

RESULTS: After excluding …

Giant Renal Cell Carcinoma In A Patient With Ipsilateral Lower Limb Hypertrophic Lichen Planus; Case Report And Literature Review, Silvia Popescu, Dumitru Peța, Zoltan Janos Kövér, Dumitru Toma, Ioan-Teodor Cristea, Mihaela Anca Popescu, Oana-Denisa Bălălău, Romina-Marina Sima, Gabriel-Petre Gorecki, Călin Giurcăneanu

Journal of Mind and Medical Sciences

Renal cell carcinoma is the most common type of primary urogenital cancer, usually resistant to radiotherapy and chemotherapy. Hypertrophic lichen planus is an inflammatory dermatosis characterized by the presence of papulosquamous and intensely pruritic lesions. The association of these two conditions is unusual, being reported in the specialized literature only in a few rare cases with the onset of lichenoid lesions after patients have undergone various forms of treatment. The case of a 62-year-old male patient who was admitted for severe abdominal pain due to a giant renal tumor associated with a hypertrophic plaque located on the anterior part of …

Pituitary Adenoma Hidden By Comorbid Cataract, Len Koh Od, Megan E. Mcchesney Od, Chad E. Gosnell Od

Optometric Clinical Practice

Background: A pituitary adenoma is an abnormal growth in the pituitary gland. Pituitary adenomas are the most common cause of sellar masses accounting for approximately 10% of all intracranial neoplasms. Early visual symptom of pituitary adenoma can be hidden by comorbid cataract in elderly patients. Case Report: A 74 y.o. male presented to the eye clinic with blurry vision at all distances and has trouble with glare from lights. His best corrected visual acuity (BCVA) was 20/20^-1 OD, 20/25^-2 OS, but subjectively of poor quality. Slit lamp exam confirmed mild nuclear sclerotic cataract OU and normal fundus exam. …

Significance Of Targeting Rna Polymerase I In Intrahepatic Cholangiocarcinoma, Muhammad A. Bangash, Aun A. Bangash, Haider Ahsan, Sahir Alvi, Mudassier Ahmad, Alejandro Rincon, Samuel Owusu-Mireku, Bilal Hafeez

MEDI 9331 Scholarly Activities Clinical Years

Intrahepatic cholangiocarcinoma (IHCC) is a much-overlooked cancer with a mortality rate that has increased throughout recent years, as stated by the American Cancer Society [1]. In the United States alone, there are an estimated 8,000 adults being diagnosed with IHCC every year, with a five-year survival rate of 9% [2]. Chemotherapy options for the treatment of IHCC include systemic chemotherapy such as gemcitabine, capecitabine, and oxaliplatin. These medications carry a wide array of adverse factors that may warrant discontinuation due to the detriment to the well-being of the patient. Additionally, a broad field of therapy that may also be used, …

Tumor-Resident Lactobacillus Iners Confer Chemoradiation Resistance Through Lactate-Induced Metabolic Rewiring, Lauren E. Colbert, Molly B. El Alam, Rui Wang, Tatiana Karpinets, David Lo, Erica J. Lynn, Timothy A. Harris, Jacob H. Elnaggar, Kyoko Yoshida-Court, Katarina Tomasic, Julianna K. Bronk, Julie Sammouri, Ananta V. Yanamandra, Adilene V. Olvera, Lily G. Carlin, Travis Sims, Andrea Y. Delgado Medrano, Tatiana Cisneros Napravnik, Madison O'Hara, Daniel Lin, Chike O. Abana, Hannah X. Li, Patricia J. Eifel, Anuja Jhingran, Melissa Joyner, Lilie Lin, Lois M. Ramondetta, Andrew M. Futreal

School of Medicine Faculty Publications

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other …

Dna2 Nuclease Inhibition Confers Synthetic Lethality In Cancers With Mutant P53 And Synergizes With Parp Inhibitors, Helena Folly-Kossi, Joshua D Graves, Lidija A Wilhelms Garan, Fang-Tsyr Lin, Weei-Chin Lin

Faculty, Staff and Students Publications

UNLABELLED: The tumor suppressor p53 promotes tumor-suppressive activities including cell-cycle inhibition, apoptosis, senescence, autophagy, and DNA repair. However, somatic mutations in the TP53 gene are one of the most common alterations in human cancers. We previously showed that mutant p53 (mutp53) can bind TopBP1, an ATR activator, to attenuate its ATR-activating function. A partially defective ATR function caused by mutp53 makes cancer cells more vulnerable to inhibitors of other TopBP1-independent ATR activators, such as DNA2. DNA2 plays a role in homologous recombination (HR) repair by resecting DNA ends in double-strand breaks and preparing them for invasion of homologous duplex. Here …

Uterine Serous Carcinoma: A Rare Presentation Of An Uncommon Type Of Cancer, Shadi Jafari-Esfahani, Fatimah Bello

Research Colloquium

Introduction: Endometrial adenocarcinoma is the most common type of uterine cancer and is divided into two types; type 1 includes 80 percent of the cases while type 2 comprises 10 to 20 percent, with latter being more aggressive. Type 2 endometrial cancer is of serous or clear cell histology and abnormal uterine bleeding is the most common clinical presentation. This case portrays an infrequent presentation of uterine cancer.

Case Presentation: A 73-year-old woman with past medical history of hypertension and diabetes mellitus type 2 presents to the emergency room with chief complaint of nausea and abdominal bloating for 2 months, …

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

Faculty, Staff and Student Publications

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

Kinome Reprogramming Is A Targetable Vulnerability In Esr1 Fusion-Driven Breast Cancer, Xuxu Gou, Beom-Jun Kim, Meenakshi Anurag, Jonathan T Lei, Meggie N Young, Matthew V Holt, Diana Fandino, Craig T Vollert, Purba Singh, Mohammad A Alzubi, Anna Malovannaya, Lacey E Dobrolecki, Michael T Lewis, Shunqiang Li, Charles E Foulds, Matthew J Ellis

Faculty, Staff and Students Publications

Transcriptionally active ESR1 fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs are not directly druggable because the C-terminal estrogen/anti-estrogen-binding domain is replaced with translocated in-frame partner gene sequences that confer constitutive transactivation. To discover alternative treatments, a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) was deployed to identify druggable kinases that are upregulated by diverse ESR1-TAFs. Subsequent explorations of drug sensitivity validated RET kinase as a common therapeutic vulnerability despite remarkable ESR1-TAF C-terminal sequence and structural diversity. Organoids and xenografts from a pan-ET-resistant patient-derived xenograft model that harbors the ESR1-e6>YAP1 TAF were …

Current Perspectives On Mass Spectrometry-Based Immunopeptidomics: The Computational Angle To Tumor Antigen Discovery, Bing Zhang, Michal Bassani-Sternberg

Faculty, Staff and Students Publications

Identification of tumor antigens presented by the human leucocyte antigen (HLA) molecules is essential for the design of effective and safe cancer immunotherapies that rely on T cell recognition and killing of tumor cells. Mass spectrometry (MS)-based immunopeptidomics enables high-throughput, direct identification of HLA-bound peptides from a variety of cell lines, tumor tissues, and healthy tissues. It involves immunoaffinity purification of HLA complexes followed by MS profiling of the extracted peptides using data-dependent acquisition, data-independent acquisition, or targeted approaches. By incorporating DNA, RNA, and ribosome sequencing data into immunopeptidomics data analysis, the proteogenomic approach provides a powerful means for identifying …

A Novel Prediction Model Of The Risk Of Pancreatic Cancer Among Diabetes Patients Using Multiple Clinical Data And Machine Learning, Shih-Min Chen, Phan Thanh Phuc, Phung-Anh Nguyen, Whitney Burton, Shwu-Jiuan Lin, Weei-Chin Lin, Christine Y Lu, Min-Huei Hsu, Chi-Tsun Cheng, Jason C Hsu

Faculty, Staff and Students Publications

INTRODUCTION: Pancreatic cancer is associated with poor prognosis. Considering the increased global incidence of diabetes cases and that individuals with diabetes are considered a high-risk subpopulation for pancreatic cancer, it is critical to detect the risk of pancreatic cancer within populations of person living = with diabetes. This study aimed to develop a novel prediction model for pancreatic cancer risk among patients with diabetes, using = a real-world database containing clinical features and employing numerous artificial intelligent approach algorithms.

METHODS: This retrospective observational study analyzed data on patients with Type 2 diabetes from a multisite Taiwanese EMR database between 2009 …