Oncology Commons^™

Targeting Igf2 To Reprogram The Tumor Microenvironment For Enhanced Viro-Immunotherapy, Min Hye Noh, Jin Muk Kang, Alexandra A Miller, Grace Nguyen, Minxin Huang, Ji Seon Shim, Alberto J Bueso-Perez, Sara A Murphy, Kimberly A Rivera-Caraballo, Yoshihiro Otani, Eunju Kim, Seung-Hee Yoo, Yuanqing Yan, Yeshavanth Banasavadi-Siddegowda, Hiroshi Nakashima, E Antonio Chiocca, Balveen Kaur, Zhongming Zhao, Tae Jin Lee, Ji Young Yoo

Student and Faculty Publications

BACKGROUND: The FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME).

METHODS: RNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance. Intracranial human and murine glioma or breast cancer brain metastasis (BCBM) tumor-bearing mouse models were employed to elucidate the mechanism underlying oHSV therapy-induced resistance.

RESULTS: Transcriptome analysis identified IGF2 as one of the top-secreted proteins following oHSV treatment. …

Escalated-Dose Radiotherapy For Unresected Locally Advanced Pancreatic Cancer: Patterns Of Care And Survival In The United States, Christopher Shi, Brian De, Hop S Tran Cao, Suyu Liu, Marcus A Florez, Ramez Kouzy, Adam J Grippin, Matthew H G Katz, Ching-Wei D Tzeng, Naruhiko Ikoma, Michael P Kim, Sunyoung Lee, Jason Willis, Sonal S Noticewala, Bruce D Minsky, Grace L Smith, Emma B Holliday, Cullen M Taniguchi, Albert C Koong, Prajnan Das, Ethan B Ludmir, Eugene J Koay

Student and Faculty Publications

INTRODUCTION: With locally advanced pancreatic cancer (LAPC), uncontrolled local tumor growth frequently leads to mortality. Advancements in radiotherapy (RT) techniques have enabled conformal delivery of escalated-dose RT (EDR), which may have potential local control and overall survival (OS) benefits based on retrospective and early prospective studies. With evidence for EDR emerging, we characterized the adoption of EDR across the United States and its associated outcomes.

METHODS: We searched the National Cancer Database for nonsurgically managed LAPC patients diagnosed between 2004 and 2019. Pancreas-directed RT with biologically effective doses (BED10) ≥39 and ≤70 Gy was labeled conventional-dose RT (CDR), and BED10 …

Common Variation In A Long Non-Coding Rna Gene Modulates Variation Of Circulating Tgf-Β2 Levels In Metastatic Colorectal Cancer Patients (Alliance), Julia Quintanilha, Alexander Sibley, Yingmiao Liu, Donna Niedzwiecki, Susan Halabi, Layne Rogers, Bert O'Neil, Hedy Kindler, William Kelly, Alan Venook, Howard Mcleod, Mark Ratain, Andrew Nixon, Federico Innocenti, Kouros Owzar

Department of Medical Oncology Faculty Papers

BACKGROUND: Herein, we report results from a genome-wide study conducted to identify protein quantitative trait loci (pQTL) for circulating angiogenic and inflammatory protein markers in patients with metastatic colorectal cancer (mCRC). The study was conducted using genotype, protein marker, and baseline clinical and demographic data from CALGB/SWOG 80405 (Alliance), a randomized phase III study designed to assess outcomes of adding VEGF or EGFR inhibitors to systemic chemotherapy in mCRC patients. Germline DNA derived from blood was genotyped on whole-genome array platforms. The abundance of protein markers was quantified using a multiplex enzyme-linked immunosorbent assay from plasma derived from peripheral venous …

Keratin 17 Modulates The Immune Topography Of Pancreatic Cancer, Lyanne Delgado-Coka, Michael Horowitz, Mariana Torrente-Goncalves, Lucia Roa-Peña, Cindy Leiton, Mahmudul Hasan, Sruthi Babu, Danielle Fassler, Jaymie Oentoro, Ji-Dong Bai, Emanuel Petricoin, Lynn Matrisian, Edik Matthew Blais, Natalia Marchenko, Felicia Allard, Wei Jiang, Brent Larson, Andrew Hendifar, Chao Chen, Shahira Abousamra, Dimitris Samaras, Tahsin Kurc, Joel Saltz, Luisa Escobar-Hoyos, Kenneth Shroyer

Kimmel Cancer Center Faculty Papers

BACKGROUND: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma. Thus, we hypothesized that K17 expression could also impact the immune cell response in PDAC, and that uncovering this relationship could provide insight to guide the development of …

Randomized Phase 2 Trial Of Tremelimumab And Durvalumab In Combination Versus Sequentially In Recurrent Platinum-Resistant Ovarian Cancer, Emily M Hinchcliff, Anne Knisely, Naomi Adjei, Bryan Fellman, Ying Yuan, Ami Patel, Cai Xu, Shannon N Westin, Anil K Sood, Pamela T Soliman, Aaron Shafer, Nicole D Fleming, David M Gershenson, Raghunandan Vikram, Tharakeswara Bathala, David Vining, Dhakshina M Ganeshan, Karen H Lu, Charlotte C Sun, Larissa A Meyer, Amir A Jazaeri

Student and Faculty Publications

BACKGROUND: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC).

METHODS: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end …

Incidental Ring-Hyperenhancing Liver Micronodules At Ct Hepatic Arteriography-Guided Percutaneous Thermal Ablation Of Colorectal Liver Metastases, Jessica Albuquerque, Yuan-Mao Lin, Iwan Paolucci, Caleb S O'Connor, Ching-Wei Tzeng, Jean-Nicolas Vauthey, Kristy K Brock, Bruno C Odisio

Student and Faculty Publications

CT during hepatic arteriography (CTHA) is a highly sensitive imaging method for detecting colorectal liver metastases (CLMs), which supports its use during percutaneous thermal liver ablation. In contrast to its high sensitivity, its specificity for incidental small CLMs not detected at preablation cross-sectional imaging is believed to be low given the absence of specific imaging signatures and the common presence of pseudolesions. In this retrospective study of 22 patients (mean age, 55 years ± 10.6 [SD]; 63.6% male, 36.4% female) with CLMs undergoing CTHA-guided microwave percutaneous thermal ablation between November 2017 and October 2022, the authors provided a definition of …

Canadian French Translation And Validation Of The Neck Dissection Impairment Index: A Quality Of Life Measure For The Surgical Oncology Population, Michel Khoury, William Guertin, Cameo Hao, Mikhail Saltychev, Tareck Ayad, Eric Bissada, Apostolos Christopoulos, Sami Moubayed, Marie-Jo Olivier, Douglas Chepeha, Stephen Y Lai, Anastasios Maniakas

Student and Faculty Publications

BACKGROUND: Neck dissections (ND) are a routine procedure in head and neck oncology. Given the postoperative functional impact that some patients experience, it is imperative to identify and track quality of life (QoL) symptomatology to tailor each patient's therapeutic needs. To date, there is no validated French-Canadian questionnaire for this patient-population. We therefore sought to translate and validate the Neck Dissection Impairment Index (NDII) in Canadian French.

METHODS: A 3-phased approach was used. Phase 1: The NDII was translated from English to Canadian French using a "forward and backward" translational technique following international guidelines. Phase 2: A cognitive debriefing session …

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

Student and Faculty 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 …

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

Student and Faculty 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 …

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

Student and Faculty 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 …

Renal Cell Carcinoma Unclassified With Medullary Phenotype In A Patient With Neurofibromatosis Type 2, Sanila Sarkar, Whitney Throckmorton, Racheal Bingham, Pavlos Msaouel, Giannicola Genovese, John Slopis, Priya Rao, Zsila Sadighi, Cynthia E Herzog

Student and Faculty Publications

We present, to our knowledge, the first reported case of germline neurofibromatosis Type 2 (NF2) associated with renal cell carcinoma unclassified with medullary phenotype (RCCU-MP) with somatic loss by immunohistochemistry of the SMARCB1 tumor suppressor gene located centromeric to NF2 on chromosome 22q. Our patient is a 15-year-old with germline neurofibromatosis Type 2 (NF2) confirmed by pathogenic mutation of c.-854-??46+??deletion. Her NF2 history is positive for a right optic nerve sheath meningioma, CNIII schwannoma requiring radiation therapy and post gross total resection of right frontotemporal anaplastic meningioma followed by radiation. At age 15 she developed new onset weight loss and …

Outcomes Of Gynecologic Cancer Surgery During The Covid-19 Pandemic: An International, Multicenter, Prospective Covidsurg-Gynecologic Oncology Cancer Study, Christina Fotopoulou, Tabassum Khan, Juraj Bracinik, James Glasbey, Nadeem Abu-Rustum, Luis Chiva, Anna Fagotti, Keiichi Fujiwara, Rahel Ghebre, Murat Gutelkin, Thomas O Konney, Joseph Ng, Rene Pareja, Rajkumar Kottayasamy Seenivasagam, Jalid Sehouli, Shylasree T S Surappa, Aneel Bhangu, Elaine Leung, Sudha Sundar

Student and Faculty Publications

BACKGROUND: The CovidSurg-Cancer Consortium aimed to explore the impact of COVID-19 in surgical patients and services for solid cancers at the start of the pandemic. The CovidSurg-Gynecologic Oncology Cancer subgroup was particularly concerned about the magnitude of adverse outcomes caused by the disrupted surgical gynecologic cancer care during the COVID-19 pandemic, which are currently unclear.

OBJECTIVE: This study aimed to evaluate the changes in care and short-term outcomes of surgical patients with gynecologic cancers during the COVID-19 pandemic. We hypothesized that the COVID-19 pandemic had led to a delay in surgical cancer care, especially in patients who required more extensive …

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

Journal Articles: Eppley Institute

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

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

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

Collagen Fiber Regulation In Human Pediatric Aortic Valve Development And Disease, Cassandra L. Clift, Yan Ru Su, David Bichell, Heather Jensen Smith, Jennifer R. Bethard, Kim Norris-Caneda, Susana Comte-Walters, Lauren E. Ball, Michael A. Hollingsworth, Anand S. Mehta, Richard R. Drake, Peggi M. Angel

Journal Articles: Eppley Institute

Congenital aortic valve stenosis (CAVS) affects up to 10% of the world population without medical therapies to treat the disease. New molecular targets are continually being sought that can halt CAVS progression. Collagen deregulation is a hallmark of CAVS yet remains mostly undefined. Here, histological studies were paired with high resolution accurate mass (HRAM) collagen-targeting proteomics to investigate collagen fiber production with collagen regulation associated with human AV development and pediatric end-stage CAVS (pCAVS). Histological studies identified collagen fiber realignment and unique regions of high-density collagen in pCAVS. Proteomic analysis reported specific collagen peptides are modified by hydroxylated prolines (HYP), …

Targeting The Tumor Core: Hypoxia-Responsive Nanoparticles For The Delivery Of Chemotherapy To Pancreatic Tumors, Matthew I. Confeld, Babak Mamnoon, Li Feng, Heather Jensen Smith, Priyanka Ray, James Froberg, Jiha Kim, Michael A. Hollingsworth, Mohiuddin Quadir, Yongki Choi, Sanku Mallik

Journal Articles: Eppley Institute

In pancreatic ductal adenocarcinoma (PDAC), early onset of hypoxia triggers remodeling of the extracellular matrix, epithelial-to-mesenchymal transition, increased cell survival, the formation of cancer stem cells, and drug resistance. Hypoxia in PDAC is also associated with the development of collagen-rich, fibrous extracellular stroma (desmoplasia), resulting in severely impaired drug penetration. To overcome these daunting challenges, we created polymer nanoparticles (polymersomes) that target and penetrate pancreatic tumors, reach the hypoxic niches, undergo rapid structural destabilization, and release the encapsulated drugs. In vitro studies indicated a high cellular uptake of the polymersomes and increased cytotoxicity of the drugs under hypoxia compared to …

Inhibition Of Geranylgeranyl Diphosphate Synthase Is A Novel Therapeutic Strategy For Pancreatic Ductal Adenocarcinoma, Staci L. Haney, Michelle L. Varney, Yashpal S. Chhonker, Simon Shin, Kamiya Mehla, Ayrianne J. Crawford, Heather Jensen Smith, Lynette M. Smith, Daryl J. Murry, Michael A. Hollingsworth, Sarah A. Holstein

Journal Articles: Eppley Institute

Rab proteins play an essential role in regulating intracellular membrane trafficking processes. Rab activity is dependent upon geranylgeranylation, a post-translational modification that involves the addition of 20-carbon isoprenoid chains via the enzyme geranylgeranyl transferase (GGTase) II. We have focused on the development of inhibitors against geranylgeranyl diphosphate synthase (GGDPS), which generates the isoprenoid donor (GGPP), as anti-Rab agents. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abnormal mucin production and these mucins play important roles in tumor development, metastasis and chemo-resistance. We hypothesized that GGDPS inhibitor (GGDPSi) treatment would induce PDAC cell death by disrupting mucin trafficking, thereby inducing the unfolded …

Genomic Prediction Of Relapse In Recipients Of Allogeneic Haematopoietic Stem Cell Transplantation., J Ritari, K Hyvärinen, S Koskela, M Itälä-Remes, R Niittyvuopio, A Nihtinen, U Salmenniemi, M Putkonen, L Volin, T Kwan, T Pastinen, J Partanen

Manuscripts, Articles, Book Chapters and Other Papers

Allogeneic haematopoietic stem cell transplantation currently represents the primary potentially curative treatment for cancers of the blood and bone marrow. While relapse occurs in approximately 30% of patients, few risk-modifying genetic variants have been identified. The present study evaluates the predictive potential of patient genetics on relapse risk in a genome-wide manner. We studied 151 graft recipients with HLA-matched sibling donors by sequencing the whole-exome, active immunoregulatory regions, and the full MHC region. To assess the predictive capability and contributions of SNPs and INDELs, we employed machine learning and a feature selection approach in a cross-validation framework to discover the …

A Brief Report Of Immunohistochemical Markers To Identify Aggressive Hepatoblastoma., Vivekanand Singh, Michelle Manalang, Meenal Singh, Udayan Apte

Manuscripts, Articles, Book Chapters and Other Papers

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Although survival of patients has improved significantly over the last 2 decades, a significant number of patients do not respond to standard chemotherapy. We conducted a pilot study to understand if there was immunophenotypic difference between tumors that respond well to chemotherapy versus that do not. We selected 10 cases of HB from children presenting at our hospital. All patients had initial tissue diagnosis, underwent chemotherapy followed by surgical resection. The cases were divided into 2 groups: aggressive group with 5 cases (all of which had a poor response …

Microscale Gene Expression Analysis Of Tumor-Associated Macrophages, Kuldeep S. Attri, Kamiya Mehla, Surendra K. Shukla, Pankaj K. Singh

Journal Articles: Eppley Institute

Macrophages, apart from being the key effector cells of the innate immune system, also play critical roles during the development and progression of various complex diseases, including cancer. Tumor-associated macrophages, infiltrate tumors during different stages of cancer progression to regulate motility, invasion, and intravasation to metastatic sites. Macrophages can exist in different polarization states associated with unique function in tumors. Since tumor-associated macrophages constitute a very small proportion of tumor cells, analysis of gene expression pattern using normal extraction buffer-based methods remains a challenging task. Therefore, it is imperative to develop low-throughput strategies to investigate transcriptional regulations from a small …

Family Strategies To Support Siblings Of Pediatric Hematopoietic Stem Cell Transplant Patients., Taylor E. White, Kristopher A. Hendershot, Margie D. Dixon, Wendy Pelletier, Ann Haight, Kristin Stegenga, Melissa A. Alderfer, Lydia Cox, Jeffrey M. Switchenko, Pamela Hinds, Rebecca D. Pentz

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To describe the strategies families report using to address the needs and concerns of siblings of children, adolescents, and young adults undergoing hematopoietic stem cell transplant (HSCT).

METHODS: A secondary semantic analysis was conducted of 86 qualitative interviews with family members of children, adolescents, and young adults undergoing HSCT at 4 HSCT centers and supplemented with a primary analysis of 38 additional targeted qualitative interviews (23 family members, 15 health care professionals) conducted at the primary center. Analyses focused on sibling issues and the strategies families use to address these issues.

RESULTS: The sibling issues identified included: (1) feeling …

The Distinct Metabolic Phenotype Of Lung Squamous Cell Carcinoma Defines Selective Vulnerability To Glycolytic Inhibition, Justin Goodwin, Michael L. Neugent, Shin Yup Lee, Joshua H. Choe, Hyunsung Choi, Dana M. R. Jenkins, Robin J. Ruthenborg, Maddox W. Robinson, Ji Yun Jeong, Masaki Wake, Hajime Abe, Norihiko Takeda, Hiroko Endo, Masahiro Inoue, Zhenyu Xuan, Hyuntae Yoo, Min Chen, Jung-Mo Ahn, John D. Minna, Kristi L. Helke, Pankaj K. Singh, David B. Shackelford, Jung-Whan Kim

Journal Articles: Eppley Institute

Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, …

Mir-155 Expression And Correlation With Clinical Outcome In Pediatric Aml: A Report From Children's Oncology Group., Ranjani Ramamurthy, Maya Hughes, Valerie Morris, Hamid Bolouri, Robert B. Gerbing, Yi-Cheng Wang, Michael R. Loken, Susana C. Raimondi, Betsy A. Hirsch, A S. Gamis, Vivian G. Oehler, Todd A. Alonzo, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Aberrant expression of microRNA-155 (miR-155) has been implicated in acute myeloid leukemia (AML) and associated with clinical outcome.

PROCEDURE: We evaluated miR-155 expression in 198 children with normal karyotype AML (NK-AML) enrolled in Children's Oncology Group (COG) AML trial AAML0531 and correlated miR-155 expression levels with disease characteristics and clinical outcome. Patients were divided into quartiles (Q1-Q4) based on miR-155 expression level, and disease characteristics were then evaluated and correlated with miR-155 expression.

RESULTS: MiR-155 expression varied over 4-log10-fold range relative to its expression in normal marrow with a median expression level of 0.825 (range 0.043-25.630) for the entire …

Shorter Remission Telomere Length Predicts Delayed Neutrophil Recovery After Acute Myeloid Leukemia Therapy: A Report From The Children's Oncology Group., Robert B. Gerbing, Todd A. Alonzo, Lillian Sung, Alan S. Gamis, Soheil Meshinchi, Sharon E. Plon, Alison A. Bertuch, Maria M. Gramatges

Manuscripts, Articles, Book Chapters and Other Papers

Purpose Suboptimal outcomes for children with acute myeloid leukemia (AML) necessitate maximally intensive therapy. Consequently, serious adverse events, such as prolonged periods of profound myelosuppression, contribute to AML treatment-related mortality. Telomeres, the repetitive DNA-protein structures at chromosome ends, influence cellular replicative capacity in that critically short telomeres can induce cell senescence or apoptosis. Our objective was to evaluate the impact of telomere length on duration of post-therapy neutropenia in a pediatric AML cohort. Patients and Methods Patients were diagnosed with de novo AML, enrolled in Children's Oncology Group study AAML0531, and included those with (n = 53) and without (n …

Association Between Prolonged Neutropenia And Reduced Relapse Risk In Pediatric Aml: A Report From The Children's Oncology Group., Lillian Sung, Richard Aplenc, Todd A. Alonzo, Robert B. Gerbing, Yi-Cheng Wang, Soheil Meshinchi, A S. Gamis

Manuscripts, Articles, Book Chapters and Other Papers

Objective was to describe the relationship between the number of sterile site infections and duration of neutropenia during the first four cycles of chemotherapy and the risk of recurrence and overall survival in children with newly diagnosed acute myeloid leukemia (AML). AAML0531 was a Children's Oncology Group randomized phase 3 clinical trial that included 1022 children with de novo AML. For this analysis, we focused on non-Down syndrome favorable and standard risk patients who completed at least 4 cycles of chemotherapy without recurrence or withdrawal during protocol therapy. Those receiving hematopoietic stem cell transplantation in first remission were excluded. Five …

Processing Information After A Child's Cancer Diagnosis-How Parents Learn., Cheryl C. Rodgers, Kristin Stegenga, Janice S. Withycombe, Karen Sachse, Katherine Patterson Kelly

Manuscripts, Articles, Book Chapters and Other Papers

Parents of a child newly diagnosed with cancer must receive an extensive amount of information before their child's initial hospital discharge; however, little is known about best practices for providing this education. An interpretive descriptive study design was used to describe actual and preferred educational content, timing, and methods among parents of children newly diagnosed with cancer prior to their child's first hospital discharge. Twenty parents of children diagnosed with various malignancies participated in individual interviews 2 to 12 months after their child's diagnosis. Data were analyzed using constant comparative analysis. Education delivery occurred in a telling manner at diagnosis …

Rationale And Design Of The Children's Oncology Group (Cog) Study Alte1621: A Randomized, Placebo-Controlled Trial To Determine If Low-Dose Carvedilol Can Prevent Anthracycline-Related Left Ventricular Remodeling In Childhood Cancer Survivors At High Risk For Developing Heart Failure., Saro H. Armenian, Melissa M. Hudson, Ming Hui Chen, Steven D. Colan, Lanie Lindenfeld, George Mills, Aida Siyahian, Sarah Gelehrter, Ha Dang, Wendy Hein, Daniel M M. Green, Leslie L. Robison, F Lennie Wong, Pamela S. Douglas, Smita Bhatia

Manuscripts, Articles, Book Chapters and Other Papers

Background: Anthracyclines are widely used in the treatment of childhood cancer. One of the well-recognized side-effects of anthracycline therapy is dose-dependent cardiomyopathy that may progress to heart failure (HF) years after completion of cancer-directed therapy. This study will evaluate the efficacy of low-dose beta-blocker (carvedilol) for HF risk reduction in childhood cancer survivors at highest risk for HF. The proposed intervention has the potential to significantly reduce chronic cardiac injury via interruption of neurohormonal systems responsible for left ventricular (LV) remodeling, resulting in improved cardiac function and decreased risk of HF. The intervention is informed by previous studies demonstrating efficacy …

‘Much Clearer With Pictures’: Using Community-Based Participatory Research To Design And Test A Picture Option Grid For Underserved Patients With Breast Cancer, Marie-Anne Durand, Shama Alam, Stuart W. Grande, Glyn Elwyn

Dartmouth Scholarship

Women of low socioeconomic status (SES) diagnosed with early stage breast cancer experience decision-making, treatment and outcome disparities. Evidence suggests that decision aids can benefit underserved patients, when tailored to their needs. Our aim was to develop and test the usability, acceptability and accessibility of a pictorial encounter decision aid targeted at women of low SES diagnosed with early stage breast cancer.

Silibinin-Mediated Metabolic Reprogramming Attenuates Pancreatic Cancer-Induced Cachexia And Tumor Growth., Surendra K. Shukla, Aneesha Dasgupta, Kamiya Mehla, Venugopal Gunda, Enza Vernucci, Joshua J. Souchek, Gennifer Goode, Ryan King, Anusha Mishra, Ibha Rai, Sangeetha Nagarajan, Nina V. Chaika, Fang Yu, Surendra K. Shukla

Journal Articles: Eppley Institute

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the US. Cancer-associated cachexia is present in up to 80% of PDAC patients and is associated with aggressive disease and poor prognosis. In the present studies we evaluated an anti-cancer natural product silibinin for its effectiveness in targeting pancreatic cancer aggressiveness and the cachectic properties of pancreatic cancer cells and tumors. Our results demonstrate that silibinin inhibits pancreatic cancer cell growth in a dose-dependent manner and reduces glycolytic activity of cancer cells. Our LC-MS/MS based metabolomics data demonstrates that silibinin treatment induces global metabolic reprogramming in pancreatic …

Invariant Characteristics Of Carcinogenesis., Simon Sherman, Nirosha Rathnayake, Tengiz Mdzinarishvili

Journal Articles: Eppley Institute

Carcinogenic modeling is aimed at mathematical descriptions of cancer development in aging. In this work, we assumed that a small fraction of individuals in the population is susceptible to cancer, while the rest of the population is resistant to cancer. For individuals susceptible to cancer we adopted methods of conditional survival analyses. We performed computational experiments using data on pancreatic, stomach, gallbladder, colon and rectum, liver, and esophagus cancers from the gastrointestinal system collected for men and women in the SEER registries during 1975-2009. In these experiments, we estimated the time period effects, the birth cohort effects, the age effects …

Clinical Significance Of A Point Mutation In Dna Polymerase Beta (Polb) Gene In Gastric Cancer., Xiaohui Tan, Hongyi Wang, Guangbin Luo, Shuyang Ren, Wenmei Li, Jiantao Cui, Harindarpal S. Gill, Sidney W. Fu, Youyong Lu

Medicine Faculty Publications

Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal …