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Impact Of Sequencing Targeted Therapies With High-Dose Interleukin-2 Immunotherapy: An Analysis Of Outcome And Survival Of Patients With Metastatic Renal Cell Carcinoma From An On-Going Observational Il-2 Clinical Trial: Proclaim, Joseph I Clark, Michael K K Wong, Howard L Kaufman, Gregory A Daniels, Michael A Morse, David F Mcdermott, Sanjiv S Agarwala, Lionel D Lewis, John H Stewart, Ulka Vaishampayan, Brendan Curti, René Gonzalez, Jose Lutzky, Venkatesh Rudraptna, Lee D Cranmer, Joanne M Jeter, Ralph J Hauke, Gerald Miletello, Mohammed M Milhem, Asim Amin, John M Richart, Mayer Fishman, Sigrun Hallmeyer, Sapna P Patel, Peter Van Veldhuizen, Neeraj Agarwal, Bret Taback, Jonathan S Treisman, Marc S Ernstoff, Jessica C Perritt, Hong Hua, Tharak B Rao, Janice P Dutcher, Sandra Aung

Articles, Abstracts, and Reports

BACKGROUND: This analysis describes the outcome for patients who received targeted therapy (TT) prior to or following high-dose interleukin-2 (HD IL-2).

PATIENTS AND METHODS: Patients with renal cell carcinoma (n = 352) receiving HD IL-2 were enrolled in Proleukin

RESULTS: Overall, there were 4% complete response (CR), 13% partial response (PR), 39% stable disease (SD), and 43% progressive disease (PD) with HD IL-2. The median overall survival (mOS) was not reached in patients with CR, PR, or SD, and was 15.5 months in patients with PD (median follow-up, 21 months). Sixty-one patients had prior TT before HD IL-2 with an …

Placental Genetic Variations In Vitamin D Metabolism And Birthweight., Tsegaselassie Workalemahu, Sylvia E Badon, Michal Dishi-Galitzky, Chunfang Qiu, Michelle A Williams, Tanya Sorensen, Daniel A Enquobahrie

Articles, Abstracts, and Reports

INTRODUCTION: Vitamin D has pleiotropic functions that regulate fetal growth and development. We investigated associations of common placental genetic variations in vitamin D metabolism with birthweight.

METHODS: The study was conducted among participants (506 maternal-infant pairs) of a pregnancy cohort study. Data were collected using interviewer-administered questionnaires and post-delivery medical record abstraction. DNA, extracted from placental samples collected at delivery, was genotyped for eight single nucleotide polymorphisms (SNPs) in five vitamin D metabolism genes (CUBN, LRP2, VDR, GC, and CYP2R1). Linear and logistic regression models were used to evaluate associations of SNPs with birthweight and risk of low birthweight, respectively. …

Qualitative Study Of Primary Care Clinicians' Views On Point-Of-Care Testing For C-Reactive Protein For Acute Respiratory Tract Infections In Family Medicine., Victoria Hardy, Matthew Thompson, Gina A Keppel, William Alto, M Ashworth Dirac, Jon Neher, Christopher Sanford, Jaime Hornecker, Allison Cole

Articles, Abstracts, and Reports

OBJECTIVE: To explore clinicians views of the barriers and facilitators to use of C-reactive protein (CRP) point-of-care tests (POCT) in US family medicine clinics for the management of acute respiratory tract infections (ARTIs) in adults.

SETTING: Five family medicine clinics across two US states.

PARTICIPANTS: 30 clinicians including 18 physicians, 9 physician residents, 2 physician assistants and 1 nurse practitioner, took part in the study.

DESIGN: A qualitative study using a grounded theory approach to thematically analyse focus group interviews.

RESULTS: These clinicians had limited access to diagnostic tests for patients with ARTI, and very little knowledge of CRP POCT. …

Astrocytes Promote Progression Of Breast Cancer Metastases To The Brain Via A Kiss1-Mediated Autophagy., Natalya Kaverina, Anton V Borovjagin, Zaira Kadagidze, Anatoly Baryshnikov, Maria Baryshnikova, Dmitry Malin, Dhimankrishhna Ghosh, Nameeta Shah, Danny R Welch, Patrik Gabikian, Apollon Karseladze, Charles Cobbs, Ilya V Ulasov

Articles, Abstracts, and Reports

Formation of metastases, also known as cancer dissemination, is an important stage of breast cancer (BrCa) development. KISS1 expression is associated with inhibition of metastases development. Recently we have demonstrated that BrCa metastases to the brain exhibit low levels of KISS1 expression at both mRNA and protein levels. By using multicolor immunofluorescence and coculture techniques here we show that normal adult astrocytes in the brain are capable of promoting metastatic transformation of circulating breast cancer cells localized to the brain through secretion of chemokine CXCL12. The latter was found in this study to downregulate KISS1 expression at the post-transcriptional level …

Assessing Survival And Grading The Severity Of Complications In Octogenarians Undergoing Pulmonary Lobectomy., Andrew Feczko, Elizabeth Mckeown, Jennifer L Wilson, Brian E Louie, Ralph W Aye, Jed A Gorden, Eric Vallières, Alexander S Farivar

Articles, Abstracts, and Reports

No abstract provided.

New Cancer Immunotherapy Agents In Development: A Report From An Associated Program Of The 31, Prasad S Adusumilli, Edward Cha, Mark Cornfeld, Thomas Davis, Adi Diab, Thomas W Dubensky, Elizabeth Evans, Jane L Grogan, Bryan A Irving, Rom Leidner, Shane A Olwill, Patrick Soon-Shiong, Frederic Triebel, David Tuck, Adrian Bot, Roger D Dansey, Charles G Drake, Gordon J Freeman, Ramy Ibrahim, Salil Patel, Daniel S Chen

Articles, Abstracts, and Reports

This report is a summary of 'New Cancer Immunotherapy Agents in Development' program, which took place in association with the 31st Annual Meeting of the Society for Immunotherapy of Cancer (SITC), on November 9, 2016 in National Harbor, Maryland. Presenters gave brief overviews of emerging clinical and pre-clinical immune-based agents and combinations, before participating in an extended panel discussion with multidisciplinary leaders, including members of the FDA, leading academic institutions and industrial drug developers, to consider topics relevant to the future of cancer immunotherapy.

Ion Channel Expression Patterns In Glioblastoma Stem Cells With Functional And Therapeutic Implications For Malignancy., Julia Pollak, Karan G Rai, Cory C Funk, Sonali Arora, Eunjee Lee, Jun Zhu, Nathan D Price, Patrick J Paddison, Jan-Marino Ramirez, Robert C Rostomily

Articles, Abstracts, and Reports

Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs) are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer, suggesting that ion channel expression may be perturbed in this population. However, little is known about the expression and functional relevance of ion channels that may contribute to GSC malignancy. Using RNA sequencing, we assessed the enrichment of ion channels in GSC isolates and non-tumor neural cell types. We identified a unique set of GSC-enriched ion channels using differential expression …

Cigarette Smoking And Cardio-Renal Events In Patients With Atherosclerotic Renal Artery Stenosis., Christopher A Drummond, Pamela S Brewster, Wencan He, Kaili Ren, Yanmei Xie, Katherine Tuttle, Steven T Haller, Kenneth Jamerson, Lance D Dworkin, Donald E Cutlip, Timothy P Murphy, Ralph B D'Agostino, William L Henrich, Jiang Tian, Joseph I Shapiro, Christopher J Cooper

Articles, Abstracts, and Reports

Cigarette smoking causes cardiovascular disease and is associated with poor kidney function in individuals with diabetes mellitus and primary kidney diseases. However, the association of smoking on patients with atherosclerotic renal artery stenosis has not been studied. The current study utilized data from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL, NCT00081731) clinical trial to evaluate the effects of smoking on the risk of cardio-renal events and kidney function in this population. Baseline data showed that smokers (n = 277 out of 931) were significantly younger at enrollment than non-smokers (63.3±9.1 years vs 72.4±7.8 years; p

Early Mutation Bursts In Colorectal Tumors., Junsong Zhao, Matthew P Salomon, Darryl Shibata, Christina Curtis, Kimberly Siegmund, Paul Marjoram

Articles, Abstracts, and Reports

Tumor growth is an evolutionary process involving accumulation of mutations, copy number alterations, and cancer stem cell (CSC) division and differentiation. As direct observation of this process is impossible, inference regarding when mutations occur and how stem cells divide is difficult. However, this ancestral information is encoded within the tumor itself, in the form of intratumoral heterogeneity of the tumor cell genomes. Here we present a framework that allows simulation of these processes and estimation of mutation rates at the various stages of tumor development and CSC division patterns for single-gland sequencing data from colorectal tumors. We parameterize the mutation …

Histopathology And Enhanced Detection Of Tumor Invasion Of Peritoneal Membranes., Jey-Hsin Chen, Melissa Borges

Articles, Abstracts, and Reports

Tumor invasion of the peritoneal membrane may have an adverse prognostic significance, but its histopathologic features can be diagnostically difficult to recognize. We observed that local peritoneal injury associated with tumor invasion is characterized by activation and proliferation of serosal stromal cells that express cytokeratin, a characteristic property of injured serosal membranes that may have diagnostic utility. To explore this, we examined 120 primary tumors of the gastrointestinal tract and pancreaticobiliary system using cytokeratin and elastic stains to assess for tumor invasion of peritoneal membranes. Peritoneal invasion by tumor was associated with retraction, splaying, and destruction of the elastic lamina …

Differential Phenotypes Of Memory Cd4 And Cd8 T Cells In The Spleen And Peripheral Tissues Following Immunostimulatory Therapy., Gail D Sckisel, Annie Mirsoian, Christine M Minnar, Marka R Crittenden, Brendan Curti, Jane Q Chen, Bruce R Blazar, Alexander D Borowsky, Arta M Monjazeb, William J Murphy

Articles, Abstracts, and Reports

BACKGROUND: Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative …

Preoperative Immunonutrition And Elective Colorectal Resection Outcomes., Lucas W Thornblade, Thomas K Varghese, Xu Shi, Eric K Johnson, Amir Bastawrous, Richard P Billingham, Richard Thirlby, Alessandro Fichera, David R Flum

Articles, Abstracts, and Reports

BACKGROUND: Randomized controlled trials demonstrate the efficacy of arginine-enriched nutritional supplements (immunonutrition) in reducing complications after surgery. The effectiveness of preoperative immunonutrition has not been evaluated in a community setting.

OBJECTIVE: This study aims to determine whether immunonutrition before elective colorectal surgery improves outcomes in the community at large.

DESIGN: This is a prospective cohort study with a propensity score-matched comparative effectiveness evaluation.

SETTINGS: This study was conducted in Washington State hospitals in the Surgical Care Outcomes Assessment Program from 2012 to 2015.

PATIENTS: Adults undergoing elective colorectal surgery were selected.

INTERVENTIONS: Surgeons used a preoperative checklist that recommended that …

Persuasive Interventions For Controversial Cancer Screening Recommendations: Testing A Novel Approach To Help Patients Make Evidence-Based Decisions., Barry Saver, Kathleen M Mazor, Roger Luckmann, Sarah L Cutrona, Marcela Hayes, Tatyana Gorodetsky, Nancy Esparza, Gonzalo Bacigalupe

Articles, Abstracts, and Reports

PURPOSE: We wanted to evaluate novel decision aids designed to help patients trust and accept the controversial, evidence-based, US Preventive Services Task Force recommendations about prostate cancer screening (from 2012) and mammography screening for women aged 40 to 49 years (from 2009).

METHODS: We created recorded vignettes of physician-patient discussions about prostate cancer screening and mammography, accompanied by illustrative slides, based on principles derived from preceding qualitative work and behavioral science literature. We conducted a randomized crossover study with repeated measures with 27 men aged 50 to 74 years and 35 women aged 40 to 49 years. All participants saw …

Safety And Feasibility Of Minimally Invasive Inguinal Lymph Node Dissection In Patients With Melanoma (Safe-Milnd): Report Of A Prospective Multi-Institutional Trial., James W Jakub, Alicia M Terando, Amod Sarnaik, Charlotte E Ariyan, Mark Faries, Sabino Zani, Heather B Neuman, Nabil Wasif, Jeffrey M Farma, Bruce J Averbook, Karl Y Bilimoria, Travis E Grotz, Jacob B Jake Allred, Vera J Suman, Mary Sue Brady, Douglas Tyler, Jeffrey D Wayne, Heidi Nelson

Articles, Abstracts, and Reports

BACKGROUND: Minimally invasive inguinal lymph node dissection (MILND) is a novel approach to inguinal lymphadenectomy. SAFE-MILND (NCT01500304) is a multicenter, phase I/II clinical trial evaluating the safety and feasibility of MILND for patients with melanoma in a group of surgeons newly adopting the procedure.

METHODS: Twelve melanoma surgeons from 10 institutions without any previous MILND experience, enrolled patients into a prospective study after completing specialized training including didactic lectures, participating in a hands-on cadaveric laboratory, and being provided an instructional DVD of the procedure. Complications and adverse postoperative events were graded using the National Cancer Institute (NCI) Common Terminology Criteria …

Foxc1 Is Associated With Estrogen Receptor Alpha And Affects Sensitivity Of Tamoxifen Treatment In Breast Cancer., Jinhua Wang, Yali Xu, Li Li, Lin Wang, Ru Yao, Qiang Sun, Guanhua Du

Articles, Abstracts, and Reports

FOXC1 is a member of Forkhead box transcription factors that participates in embryonic development and tumorigenesis. Our previous study demonstrated that FOXC1 was highly expressed in triple-negative breast cancer. However, it remains unclear what is the relation between FOXC1 and ERα and if FOXC1 regulates expression of ERα. To explore relation between FOXC1 and ERα and discover regulation of ERα expression by FOXC1 in breast cancer, we analyzed data assembled in the Oncomine and TCGA, and found that there was significantly higher FOXC1 expression in estrogen receptor-negative breast cancer than that in estrogen receptor-positive breast cancer. Overexpression of FOXC1 reduced …

Mutational Landscapes Of Smoking-Related Cancers In Caucasians And African Americans: Precision Oncology Perspectives At Wake Forest Baptist Comprehensive Cancer Center., Ville Kytola, Umit Topaloglu, Lance D Miller, Rhonda L Bitting, Michael M Goodman, Ralph B D Agostino, Rodwige J Desnoyers, Carol Albright, George Yacoub, Shadi A Qasem, Barry Deyoung, Vesteinn Thorsson, Ilya Shmulevich, Meng Yang, Anastasia Shcherban, Matthew Pagni, Liang Liu, Matti Nykter, Kexin Chen, Gregory A Hawkins, Stefan C Grant, W Jeffrey Petty, Angela Tatiana Alistar, Edward A Levine, Edgar D Staren, Carl D Langefeld, Vincent Miller, Gaurav Singal, Robin M Petro, Mac Robinson, William Blackstock, Bayard L Powell, Lynne I Wagner, Kristie L Foley, Edward Abraham, Boris Pasche, Wei Zhang

Articles, Abstracts, and Reports

Background: Cancers related to tobacco use and African-American ancestry are under-characterized by genomics. This gap in precision oncology research represents a major challenge in the health disparities in the United States. Methods: The Precision Oncology trial at the Wake Forest Baptist Comprehensive Cancer Center enrolled 431 cancer patients from March 2015 to May 2016. The composition of these patients consists of a high representation of tobacco-related cancers (e.g., lung, colorectal, and bladder) and African-American ancestry (13.5%). Tumors were sequenced to identify mutations to gain insight into genetic alterations associated with smoking and/or African-American ancestry. Results: Tobacco-related cancers exhibit a high …

Sting Expression And Response To Treatment With Sting Ligands In Premalignant And Malignant Disease., Jason R Baird, Zipei Feng, Hong D Xiao, David Friedman, Ben Cottam, Bernard A Fox, Gwen Kramer, Rom S Leidner, Richard Bryan Bell, Kristina H Young, Marka R Crittenden, Michael J Gough

Articles, Abstracts, and Reports

Human papilloma virus positive (HPV+) tumors represent a large proportion of anal, vulvar, vaginal, cervical and head and neck squamous carcinomas (HNSCC) and late stage invasive disease is thought to originate from a premalignant state. Cyclic dinucleotides that activate STimulator of INterferon Genes (STING) have been shown to cause rapid regression of a range of advanced tumors. We aimed to investigate STING ligands as a novel treatment for papilloma. We tested therapies in a spontaneous mouse model of papilloma of the face and anogenital region that histologically resembles human HPV-associated papilloma. We demonstrate that STING ligands cause rapid regression of …

Does Gated Beam Delivery Impact Delivery Accuracy On An Elekta Linac?, Mohammed Jermoumi, Roger Xie, Daliang Cao, David J Housley, David M Shepard

Articles, Abstracts, and Reports

In this study, we evaluated the performance of an Elekta linac in the delivery of gated radiotherapy. Delivery accuracy was examined with an emphasis on the impact of using short gating windows (low monitor unit beam-on segments) or long beam hold times. The performance was assessed using a 20cm by 20cm open field with the radiation delivered using a range of beam-on and beam-off time periods. Gated delivery measurements were also performed for two SBRT plans delivered using volumetric modulated arc therapy (VMAT). Tests included both free-breathing based gating (covering a variety of gating windows) and simulated breath-hold based gating. …

Risk Of Glucose Intolerance And Gestational Diabetes Mellitus In Relation To Maternal Habitual Snoring During Early Pregnancy., Chunfang Qiu, Wayne Lawrence, Bizu Gelaye, Lee Stoner, Ihunnaya O Frederick, Daniel A Enquobahrie, Tanya K Sorensen, Michelle A Williams

Articles, Abstracts, and Reports

BACKGROUND: Obstructive sleep apnea (OSA) or habitual snoring is known to be associated with impaired glucose tolerance and type 2 diabetes among both men and non-pregnant women. We examined the association of habitual snoring during early pregnancy with risk of impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM).

METHODS: A cohort of 1,579 women was interviewed during early pregnancy. We collected information about snoring frequency during early pregnancy. Results from screening and diagnostic tests for IGT and GDM were abstracted from medical records. Multivariate logistic regression models were fitted to estimate odds ratios (OR) and 95% confidence intervals (95% …