Medical Specialties Commons^™

Tumor-Released Autophagosomes Induces Cd4, Yong-Qiang Chen, Peng-Cheng Li, Ning Pan, Rong Gao, Zhi-Fa Wen, Tian-Yu Zhang, Fang Huang, Fang-Yuan Wu, Xi-Long Ou, Jin-Ping Zhang, Xue-Jun Zhu, Hong-Ming Hu, Kang Chen, Yun-Lang Cai, Li-Xin Wang

Articles, Abstracts, and Reports

BACKGROUND: CD4

METHODS: TRAPs isolated from tumor cell lines and pleural effusions or ascites of cancer patients were incubated with CD4

RESULTS: Heat shock protein 90α (HSP90α) on the surface of TRAPs from malignant effusions of cancer patients and tumor cell lines stimulated CD4

CONCLUSIONS: HSP90α on the surface of TRAPs programs the immunosuppressive functions of CD4

Blockade Of Tgf-Β Signaling To Enhance The Antitumor Response Is Accompanied By Dysregulation Of The Functional Activity Of Cd4, Magdalena J Polanczyk, Edwin Walker, Daniel Haley, Bella S Guerrouahen, Emmanuel T Akporiaye

Articles, Abstracts, and Reports

BACKGROUND: The pleiotropic cytokine, transforming growth factor (TGF)-β, and CD4

METHODS: Using BALB/c, FoxP3eGFP and Rag

RESULTS: SM16 abrogates TGF-β-induced Treg generation in vitro but does not prevent global homeostatic expansion of CD4

CONCLUSIONS: These findings suggest that blockade of TGF-β signaling is a potentially useful strategy for blunting Treg function to enhance the anti-tumor response. Our data further suggest that the overall dampening of Treg function may involve the expansion of a quiescent Treg precursor population, which is CD4

From Vaccine Vector To Oncomodulation: Understanding The Complex Interplay Between Cmv And Cancer., Nicole A. Wilski, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent, but generally asymptomatic, infection in most people in the world. However, CMV drives and sustains extremely large numbers of antigen-specific T cells and is, therefore, emerging as an exciting platform for vaccines against infectious diseases and cancer. Indeed, pre-clinical data strongly suggest that CMV-based vaccines can sustain protective CD8+ T cell and antibody responses. In the context of vaccines for infectious diseases, substantial pre-clinical studies have elucidated the effcacy and protective mechanisms of CMV-based vaccines, including in non-human primate models of various infections. In the context of cancer vaccines, however, much …

Myc-Mediated Transcriptional Regulation Of The Mitochondrial Chaperone Trap1 Controls Primary And Metastatic Tumor Growth., Ekta Agarwal, Brian J. Altman, Jae Ho Seo, Jagadish C. Ghosh, Andrew V Kossenkov, Hsin-Yao Tang, Shiv Ram Krishn, Lucia R. Languino, Dmitry I. Gabrilovich, David W. Speicher, Chi V. Dang, Dario C. Altieri

Department of Cancer Biology Faculty Papers

The role of mitochondria in cancer continues to be debated, and whether exploitation of mitochondrial functions is a general hallmark of malignancy or a tumor- or context-specific response is still unknown. Using a variety of cancer cell lines and several technical approaches, including siRNA-mediated gene silencing, ChIP assays, global metabolomics and focused metabolite analyses, bioenergetics, and cell viability assays, we show that two oncogenic Myc proteins, c-Myc and N-Myc, transcriptionally control the expression of the mitochondrial chaperone TNFR-associated protein- 1 (TRAP1) in cancer. In turn, this Myc-mediated regulation preserved the folding and function of mitochondrial oxidative phosphorylation (OXPHOS) complex II …

Edb-Fn Targeted Peptide–Drug Conjugates For Use Against Prostate Cancer, Shang Eun Park, Kiumars Shamloo, Timothy A. Kristedja, Shaban Darwish, Marco Bisoffi, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Prostate cancer (PCa) is the most common malignancy in men and is the leading cause of cancer-related male mortality. A disulfide cyclic peptide ligand [CTVRTSADC] 1 has been previously found to target extra domain B of fibronectin (EDB-FN) in the extracellular matrix that can dierentiate aggressive PCa from benign prostatic hyperplasia. We synthesized and optimized the stability of ligand 1 by amide cyclization to obtain [KTVRTSADE] 8 using Fmoc/tBu solid-phase chemistry. Optimized targeting ligand 8 was found to be stable in phosphate buered saline (PBS, pH 6.5, 7.0, and 7.5) and under redox conditions, with a half-life longer than 8 …

Correction To: Toward A Comprehensive View Of Cancer Immune Responsiveness: A Synopsis From The Sitc Workshop., Davide Bedognetti, Michele Ceccarelli, Lorenzo Galluzzi, Rongze Lu, Karolina Palucka, Josue Samayoa, Stefani Spranger, Sarah Warren, Kwok-Kin Wong, Elad Ziv, Diego Chowell, Lisa M Coussens, Daniel D De Carvalho, David G Denardo, Jérôme Galon, Howard L Kaufman, Tomas Kirchhoff, Michael T Lotze, Jason J Luke, Andy J Minn, Katerina Politi, Leonard D Shultz, Richard Simon, Vésteinn Thorsson, Joanne B Weidhaas, Maria Libera Ascierto, Paolo Antonio Ascierto, James M Barnes, Valentin Barsan, Praveen K Bommareddy, Adrian Bot, Sarah E Church, Gennaro Ciliberto, Andrea De Maria, Dobrin Draganov, Winson S Ho, Heather M Mcgee, Anne Monette, Joseph F Murphy, Paola Nisticò, Wungki Park, Maulik Patel, Michael Quigley, Laszlo Radvanyi, Harry Raftopoulos, Nils-Petter Rudqvist, Alexandra Snyder, Randy F Sweis, Sara Valpione, Roberta Zappasodi, Lisa H Butterfield, Mary L Disis, Bernard A Fox, Alessandra Cesano, Francesco M Marincola

Articles, Abstracts, and Reports

Following publication of the original article [1], the author reported that an author name, Roberta Zappasodi, was missed in the authorship list.

Prevalence Of Suspected Hereditary Cancer Syndromes And Germline Mutations Among A Diverse Cohort Of Probands Reporting A Family History Of Prostate Cancer: Toward Informing Cascade Testing For Men., Thenappan Chandrasekar, Laura Gross, Leonard G. Gomella, Sarah E. Hegarty, Joon Yau Leong, Veda N. Giri

Department of Urology Faculty Papers

BACKGROUND: Prostate cancer (PCa) is increasingly recognized as part of hereditary cancer syndromes (HCSs). HCS prevalence among diverse probands seeking genetic evaluation with PCa family history (FHx) has not been reported and has implications for cascade genetic testing.

OBJECTIVE: To evaluate the rates of HCSs among probands reporting PCa FHx and germline mutations among probands.

DESIGN, SETTING, AND PARTICIPANTS: A prospective genetic testing database queried for individuals with PCa FHx. Pedigrees analyzed for three HCSs: hereditary breast and ovarian cancer (HBOC), hereditary PCa, and Lynch syndrome.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations between HCS overall, and with plausible link to …

The Current State Of Molecular Testing In The Treatment Of Patients With Solid Tumors, 2019., Wafik S El-Deiry, Richard M Goldberg, Heinz-Josef Lenz, Anthony F Shields, Geoffrey T Gibney, Antoinette R Tan, Jubilee Brown, Burton Eisenberg, Elisabeth I Heath, Surasak Phuphanich, Edward Kim, Andrew J Brenner, John L Marshall

Articles, Abstracts, and Reports

The world of molecular profiling has undergone revolutionary changes over the last few years as knowledge, technology, and even standard clinical practice have evolved. Broad molecular profiling is now nearly essential for all patients with metastatic solid tumors. New agents have been approved based on molecular testing instead of tumor site of origin. Molecular profiling methodologies have likewise changed such that tests that were performed on patients a few years ago are no longer complete and possibly inaccurate today. As with all rapid change, medical providers can quickly fall behind or struggle to find up-to-date sources to ensure he or …

Diagnosis Of Non-Small Cell Lung Cancer For Early Stage Asymptomatic Patients., Cherylle Goebel, Christopher L Louden, Robert Mckenna, Osita Onugha, Andrew Wachtel, Thomas Long

Articles, Abstracts, and Reports

BACKGROUND/AIM: In 2016 in the United States, 7 of 10 patients were estimated to die following lung cancer diagnosis. This is due to a lack of a reliable screening method that detects early-stage lung cancer. Our aim is to accurately detect early stage lung cancer using algorithms and protein biomarkers.

PATIENTS AND METHODS: A total of 1,479 human plasma samples were processed using a multiplex immunoassay platform. 82 biomarkers and 6 algorithms were explored. There were 351 NSCLC samples (90.3% Stage I, 2.3% Stage II, and 7.4% Stage III/IV).

RESULTS: We identified 33 protein biomarkers and developed a classifier using …

Survivin Is A Prognostic Marker And Therapeutic Target For Extranodal, Nasal-Type Natural Killer/T Cell Lymphoma., Li Zhang, Yi Wei, Xiaowei Yan, Na Li, Haolan Song, Li Yang, Yang Wu, Yu-Feng Xi, Hua-Wei Weng, Jian-Hua Li, Edward H Lin, Li-Qun Zou

Articles, Abstracts, and Reports

Background: The relationship between survivin and extranodal, nasal-type natural killer/T cell lymphoma (ENKTCL) was unclearly established yet. We here studied the potential prognostic roles of survivin and its implication as a target in ENKTCL therapy.

Methods: ENKTCL patients' peripheral blood were collected and tested by ELISA. ENKTCL cell lines were cultured with or without survivin inhibitor and tested by MTT and Flow cytometry. According to the gene expression profiles from the ArrayExpress Archive under E-TABM-702, survivin co-regulated cluster was established by Coupled Two-way Clustering Algorithm.

Results: Seventeen point six percent of total 17 ENKTCL patients were serum survivin-positive. These patients …

The Write Stuff - Summer 2019 (Vol. 16, No. 3), Research Medical Library

Write Stuff 2019

• Using Research Resource Identifiers (RRIDs) to enhance rigor and reproducibility
• Court ruling sheds light on publishing giant OMICS International
• Manuscript presentation tips to improve the peer review process
• How to insert Greek letters, symbols, and other special characters in Word documents
• Changes to Plan S give researchers and publishers time to adapt
• Unusual terms used in scientific writing and publishing: Hanging indent

Metastatic Breast Cancer In Kenya: Presentation, Pathologic Characteristics, And Patterns-Findings From A Tertiary Cancer Center, Etoroabasi Ekpe, Asim Jamal, Jasmit Shah, Judith S. Jacobson, Shahin Sayed

Internal Medicine, East Africa

Purpose: The purpose of this research was to describe the sociodemographic and clinical characteristics of Kenyan women with metastatic breast cancer diagnosed and treated at Aga Khan University Hospital in Nairobi, Kenya from 2012 to 2018.

Patients and Methods: We reviewed charts of Kenyan women with metastatic breast cancer and analyzed sociodemographic data, breast cancer risk factors, and tumor characteristics associated with stage at diagnosis, receptor status (ie, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 [HER2]), and site of metastasis using χ2, analysis of variance, two-sample t tests, and logistic regressions.

Results: A total of 125 …

Phospholipases D: Making Sense Of Redundancy And Duplication, Andrew J. Morris

Internal Medicine Faculty Publications

Why have two genes when one would suffice? Evolutionary pressure means that biology, unlike government, is generally intolerant of wasted effort. Therefore, when multiple genes exist presumably they are there to provide some benefit to the organism even if that benefit is not immediately obvious to us scientists. A recent report from Raghu and colleagues (Biosci. Rep. (2018) 38, pii: BSR20181690) [1] sheds some light on one possible reason for the existence of two Phospholipases D genes in chordates when only one is present in invertebrates.

Microrna Regulation Of Epigenetic Modifiers In Breast Cancer, Brock Humphries, Zhishan Wang, Chengfeng Yang

Toxicology and Cancer Biology Faculty Publications

Epigenetics refers to the heritable changes in gene expression without a change in the DNA sequence itself. Two of these major changes include aberrant DNA methylation as well as changes to histone modification patterns. Alterations to the epigenome can drive expression of oncogenes and suppression of tumor suppressors, resulting in tumorigenesis and cancer progression. In addition to modifications of the epigenome, microRNA (miRNA) dysregulation is also a hallmark for cancer initiation and metastasis. Advances in our understanding of cancer biology demonstrate that alterations in the epigenome are not only a major cause of miRNA dysregulation in cancer, but that miRNAs …

Liver Cancer: A Leading Cause Of Cancer Death In The United States And The Role Of The 1945–1965 Birth Cohort By Ethnicity, Paulo S. Pinheiro, Karen E. Callahan, Patricia D. Jones, Cyllene Morris, Justine M. Ransdell, Deukwoo Kwon, Clyde Perry Brown, Erin N. Kobetz

Environmental & Global Health Faculty Research

No abstract provided.

M6a Mrna Demethylase Fto Regulates Melanoma Tumorigenicity And Response To Anti-Pd-1 Blockade, Seungwon Yang, Jiangbo Wei, Yan-Hong Cui, Gayoung Park, Palak Shah, Yu Deng, Andrew E. Aplin, Zhike Lu, Seungmin Hwang, Chuan He, Yu-Ying He

Department of Cancer Biology Faculty Papers

Melanoma is one of the most deadly and therapy-resistant cancers. Here we show that N⁶-methyladenosine (m⁶A) mRNA demethylation by fat mass and obesity-associated protein (FTO) increases melanoma growth and decreases response to anti-PD-1 blockade immunotherapy. FTO level is increased in human melanoma and enhances melanoma tumorigenesis in mice. FTO is induced by metabolic starvation stress through the autophagy and NF-κB pathway. Knockdown of FTO increases m⁶A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m⁶A reader YTHDF2. Knockdown of …

Outcomes Of Haploidentical Vs Matched Sibling Transplantation For Acute Myeloid Leukemia In First Complete Remission., Armin Rashidi, Mehdi Hamadani, Mei-Jie Zhang, Hai-Lin Wang, Hisham Abdel-Azim, Mahmoud Aljurf, Amer Assal, Ashish Bajel, Asad Bashey, Minoo Battiwalla, Amer M. Beitinjaneh, Nelli Bejanyan, Vijaya Raj Bhatt, Javier Bolaños-Meade, Michael Byrne, Jean-Yves Cahn, Mitchell Cairo, Stefan Ciurea, Edward Copelan, Corey Cutler, Andrew Daly, Miguel-Angel Diaz, Nosha Farhadfar, Robert P. Gale, Siddhartha Ganguly, Michael R. Grunwald, Theresa Hahn, Shahrukh Hashmi, Gerhard C. Hildebrandt, H. Kent Holland, Nasheed Hossain, Christopher G Kanakry, Mohamed A. Kharfan-Dabaja, Nandita Khera, Yener Koc, Hillard M. Lazarus, Jong-Wook Lee, Johan Maertens, Rodrigo Martino, Joseph Mcguirk, Reinhold Munker, Hemant S. Murthy, Ryotaro Nakamura, Sunita Nathan, Taiga Nishihori, Neil D. Palmisiano, Sagar Patel, Joseph Pidala, Rebecca Olin, Richard F. Olsson, Betul Oran, Olov Ringden, David Rizzieri, Jacob Rowe, Mary Lynn Savoie, Kirk R. Schultz, Sachiko Seo, Brian C. Shaffer, Anurag Singh, Melhem Solh, Keith Stockerl-Goldstein, Leo F. Verdonck, John Wagner, Edmund K. Waller, Marcos De Lima, Brenda M. Sandmaier, Mark Litzow, Dan Weisdorf, Rizwan Romee, Wael Saber

Department of Medical Oncology Faculty Papers

HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy–based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor–based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs …

A Transfer Learning Approach For Malignant Prostate Lesion Detection On Multiparametric Mri, Quan Chen, Shiliang Hu, Peiran Long, Fang Lu, Yujie Shi, Yunpeng Li

Radiation Medicine Faculty Publications

Purpose: In prostate focal therapy, it is important to accurately localize malignant lesions in order to increase biological effect of the tumor region while achieving a reduction in dose to noncancerous tissue. In this work, we proposed a transfer learning–based deep learning approach, for classification of prostate lesions in multiparametric magnetic resonance imaging images. Methods: Magnetic resonance imaging images were preprocessed to remove bias artifact and normalize the data. Two state-of-the-art deep convolutional neural network models, InceptionV3 and VGG-16, were pretrained on ImageNet data set and retuned on the multiparametric magnetic resonance imaging data set. As lesion appearances differ by …

Hemothorax And Hemorrhagic Ascites: A Rare Presentation Of Endometriosis, Harry Wang, Md

The Medicine Forum

Introduction

Endometriosis is a common diagnosis in reproductive age women characterized by the presence of endometrial tissue outside the uterine cavity.1 Although it is typically confined to the pelvis, rare manifestations involving the thorax, abdomen or pericardium have been documented.2-5 Even more rare is the concurrent presence of endometriosis- associated hemorrhagic pleural effusion and ascites, which can prove a diagnostic challenge. We describe a case of hemothorax and hemorrhagic ascites in a woman with shortness of breath and abdominal pain.

Hyperviscosity In Non-Igm Lymphoplasmacytic Lymphoma, Mario Fonseca-Paricio, Md, Sushil Chmire, Md, Adam Binder, Md

The Medicine Forum

The following is a case of how a non-IgM paraproteinemia can present with symptoms of hyperviscosity and coagulopathy, an uncommon occurrence.1-3 As this case demonstrates, this diagnosis must be considered even in patients with relatively normal coagulation laboratory results. Such pathology requires urgent treatment with plasmapheresis.

Worsening Autoimmune Neutropenia After Stopping Ibrutinib In A Patient With Chronic Lymphocytic Leukemia: Case Report And Review Of Literature, Natalie Rosen, Ba, Thomas Klumpp, Md, Sameh Gaballa, Md, Msc

The Medicine Forum

Introduction

Autoimmune cytopenia (AIC) is relatively common in patients with chronic lymphocytic leukemia occurring in 5-10% of patients during the course of their disease.1 Autoimmune hemolytic anemia (AIHA) constitutes the highest prevalence (5-10%) of CLL-associated AIC followed by idiopathic thrombocytopenic purpura (ITP) (2-5%), pure red cell aplasia (PRCA) (<1%), and autoimmune neutropenia (AIN) (<1%).2,3 The prevalence of AIN, however, may in fact be higher than reported due to a lack of awareness of the condition and difficulty in its diagnosis.4 Despite its rarity, autoimmune neutropenia can be a significant clinical challenge in patients with CLL and can increase the risk of infectious complications. Thus, the prompt diagnosis and resolution of CLL-associated AIN is essential to the management of these patients.

Ibrutinib is a selective inhibitor of Bruton tyrosine kinase and induces a durable response in patients with CLL.5 The activity of ibrutinib in CLL-associated AIC is largely unknown as pivotal clinical trials excluded patients with AIC. We report a case of a patient with CLL who experienced worsening of AIN after …

Bilateral Choroidal Metastases As Initial Presentation Of Widespread Follicular Thyroid Cancer, Jennifer Hong, Md

The Medicine Forum

Introduction

Follicular thyroid cancer (FTC) is the second most common malignancy of the thyroid gland and comprise 10-15% of all thyroid tumors; the usual mode of spread is via hematogenous dissemination with the most common sites of metastases being the lungs and bones.4 A case is presented to demonstrate the unusual presentation of follicular thyroid cancer as bilateral choroidal metastases. Although exceptional, a diagnosis of choroidal metastases should be considered in any decline in visual acuity in patients with thyroid cancer.

Preoperative Stimulation Of Resolution And Inflammation Blockade Eradicates Micrometastases., Dipak Panigrahy, Allison Gartung, Jun Yang, Haixia Yang, Molly M Gilligan, Megan L Sulciner, Swati S Bhasin, Diane R Bielenberg, Jaimie Chang, Birgitta A Schmidt, Julia Piwowarski, Anna Fishbein, Dulce Soler-Ferran, Matthew A Sparks, Steven J Staffa, Vidula Sukhatme, Bruce D Hammock, Mark W Kieran, Sui Huang, Manoj Bhasin, Charles N Serhan, Vikas P Sukhatme

Articles, Abstracts, and Reports

Cancer therapy is a double-edged sword, as surgery and chemotherapy can induce an inflammatory/immunosuppressive injury response that promotes dormancy escape and tumor recurrence. We hypothesized that these events could be altered by early blockade of the inflammatory cascade and/or by accelerating the resolution of inflammation. Preoperative, but not postoperative, administration of the nonsteroidal antiinflammatory drug ketorolac and/or resolvins, a family of specialized proresolving autacoid mediators, eliminated micrometastases in multiple tumor-resection models, resulting in long-term survival. Ketorolac unleashed anticancer T cell immunity that was augmented by immune checkpoint blockade, negated by adjuvant chemotherapy, and dependent on inhibition of the COX-1/thromboxane A2 …

Collaborative Molecular Epidemiology Study Of Metabolic Dysregulation, Dna Methylation, And Breast Cancer Risk Among Nigerian Women: Mend Study Objectives And Design, Tomi Akinyemiju, Omolola Salako, Adetola Daramola, Olusegun Alatise, Adewale Adeniyi, Gabriel Ogun, Omobolaji Ayandipo, Thomas Olajide, Olalekan Olasehinde, Olukayode Arowolo, Adewale Adisa, Oludolapo Afuwape, Aralola Olusanya, Aderemi Adegoke, Akinlolu Ojo, Trygve Tollefsbol, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

PURPOSE To elucidate the role of metabolic dysregulation and associated DNA methylation changes on breast cancer risk and aggressive subtypes among Nigerian women. We describe the design and methods of a collaborative molecular epidemiology study of breast cancer in Nigerian hospitals.

METHODS The Mechanisms for Novel and Established Risk Factors for Breast Cancer in Women of Nigerian Descent (MEND) study was designed as a matched case-control study of 350 patients, age 18 to 75 years, with newly diagnosed, treatment-naïve breast cancer and 350 age-matched healthy controls from surrounding geographic areas. Patients with breast cancer seen for initial diagnosis at four …

Extreme Peripheral Blood Plasmacytosis Mimicking Plasma Cell Leukemia As A Presenting Feature Of Angioimmunoblastic T-Cell Lymphoma (Aitl)., Kelsey Sokol, Saritha Kartan, William T. Johnson, Onder Alpdogan, Neda Nikbakht, Bradley M. Haverkos, Jerald Z. Gong, Pierluigi Porcu

Department of Medical Oncology Faculty Papers

Angioimmunoblastic T-cell lymphoma (AITL) is one of four major subtypes of nodal peripheral T cell lymphoma, characterized by its cell of origin, the follicular helper T-cell (TFH). Patients typically present with prominent constitutional (B) symptoms, generalized lymphadenopathy, hepatosplenomegaly, cytopenias, and rash. Here we present a case of a 62-year-old male with progressive cervical adenopathy, fevers and weight loss presenting with extreme polyclonal plasmacytosis and high plasma EBV viral load. While the initial presentation appeared to mimic plasma cell leukemia or severe infection, lymph node biopsy and bone marrow biopsy confirmed a diagnosis of AITL. This case highlights the heterogeneity of …

Real-World Treatment Patterns And Adverse Events In Metastatic Renal Cell Carcinoma From A Large Us Claims Database., Sumanta Pal, Jun Gong, Shivani K Mhatre, Shih-Wen Lin, Andy Surinach, Sarika Ogale, Rini Vohra, Herschel Wallen, Daniel George

Articles, Abstracts, and Reports

BACKGROUND: Vascular endothelial growth factor (VEGF), tyrosine kinase (TK) and mechanistic target of rapamycin kinase (mTOR) inhibitors are common first-line (1 L) treatments for metastatic renal cell carcinoma (mRCC). Despite treatment availability, the 5-year survival rate in patients diagnosed at the metastatic stage is only ≈ 10%. To gain contemporary insights into RCC treatment trends that may inform clinical, scientific and payer considerations, treatment patterns and adverse events (AEs) associated with 1 L therapy were examined in a retrospective, longitudinal, population-based, observational study of patients with mRCC.

METHODS: US administrative claims data (Truven Health MarketScan Commercial Databases) were used to …

Multi-Institutional Dosimetric Evaluation Of Modern Day Stereotactic Radiosurgery (Srs) Treatment Options For Multiple Brain Metastases., Irina Vergalasova, Haisong Lui, Michelle Alonso-Basanta, Lei Dong, Jun Li, Ke Nie, Wenyin Shi, Boon-Keng Kevin Teo, Yan Yu, Ning Jeff Yue, Wei Zou, Taoran Li

Department of Radiation Oncology Faculty Papers

Purpose/Objectives: There are several popular treatment options currently available for stereotactic radiosurgery (SRS) of multiple brain metastases: 60Co sources and cone collimators around a spherical geometry (GammaKnife), multi-aperture dynamic conformal arcs on a linac (BrainLab Elements™ v1.5), and volumetric arc therapy on a linac (VMAT) calculated with either the conventional optimizer or with the Varian HyperArc™ solution. This study aimed to dosimetrically compare and evaluate the differences among these treatment options in terms of dose conformity to the tumor as well as dose sparing to the surrounding normal tissues.

Methods and Materials: Sixteen patients and a total of 112 metastases …

Activation Of Lxr Receptors And Inhibition Of Trap1 Causes Synthetic Lethality In Solid Tumors, Trang Thi Thu Nguyen, Chiaki Tsuge Ishida, Enyuan Shang, Chang Shu, Elena Bianchetti, Georg Karpel-Massler, Markus D. Siegelin

Publications and Research

Cholesterol is a pivotal factor for cancer cells to entertain their relentless growth. In this case, we provide a novel strategy to inhibit tumor growth by simultaneous activation of liver-X-receptors and interference with Tumor Necrosis Factor Receptor-associated Protein 1 (TRAP1). Informed by a transcriptomic and subsequent gene set enrichment analysis, we demonstrate that inhibition of TRAP1 results in suppression of the cholesterol synthesis pathway in stem-like and established glioblastoma (GBM) cells by destabilizing the transcription factor SREBP2. Notably, TRAP1 inhibition induced cell death, which was rescued by cholesterol and mevalonate. Activation of liver X receptor (LXR) by a clinically validated …

The Implementation And Efficacy Of A Breast Cancer Wellness Group At Thomas Jefferson University Hospital, Steven Woodward, Md, Peter Altshuler, Md, Theodore N. Tsangaris, Md

House Staff Quality Improvement and Patient Safety Conference (2016-2019)

Abstract

Introduction: Breast cancer is not only a physical disease but something that affects our patients’ mental, spiritual, emotional and social wellbeing. There has been literature that demonstrates the positive benefits of exercise, social support, and nonmedical adjuncts for breast cancer patients. There is currently a lack of wellness support within the Jefferson breast cancer community.

Methods: A wellness survey will be distributed throughout the breast surgery and breast oncology clinics to assess the current level of wellness and interest in a breast cancer wellness group at TJUH. This survey will be used both before and after implementation …

A Qi Initiative To Reduce Time To Antibiotics In Oncologic Neutropenic Fever, Adam Binder, Jordan Villars

House Staff Quality Improvement and Patient Safety Conference (2016-2019)

Problem Statement

Neutropenic fever (NF) (defined as temperature of 101o F on one occasion, or 100.4o F sustained over 60 minutes in a patient with an absolute neutrophil count (ANC) less than 500, or suspected drop below 500 within 48 hours) is relatively common oncologic emergency, particularly in hematologic malignancy patients. Expert consensus is that anti-pseudomonas gram-negative antibiotics (abx) should be administered within 60 minutes of detecting neutropenic fever.

At Thomas Jefferson University Hospital (TJUH), internal guidelines for time to treatment in neutropenic fever are in line with expert consensus - 60 minutes. We found that from July 1st – …