Medical Specialties Commons^™

A Phase 1b Study Of Humanized Ks-Interleukin-2 (Huks-Il2) Immunocytokine With Cyclophosphamide In Patients With Epcam-Positive Advanced Solid Tumors., Joseph P Connor, Mihaela C Cristea, Nancy L Lewis, Lionel D Lewis, Philip B Komarnitsky, Maria R Mattiacci, Mildred Felder, Sarah Stewart, Josephine Harter, Jean Henslee-Downey, Daniel Kramer, Roland Neugebauer, Roger Stupp

Kimmel Cancer Center Faculty Papers

BACKGROUND: Humanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent.

METHODS: Phase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300 mg/m2 on day 1), and escalating doses of huKS-IL2 (0.5-4.0 mg/m2 IV continuous infusion over 4 hours) on days 2, 3, and 4 of each 21-day cycle. Safety, pharmacokinetic profile, immunogenicity, anti-tumor and biologic activity were evaluated.

RESULTS: Twenty-seven patients were treated …

Xiaoqinglong Granules As Add-On Therapy For Asthma: Latent Class Analysis Of Symptom Predictors Of Response., Qinglin Zha, Seqi Lin, Chi Zhang, Christopher Chang, Hanrong Xue, Cheng Lu, Miao Jiang, Yan Liu, Zuke Xiao, Weiyou Liu, Yunfei Shang, Jianjian Chen, Minyong Wen, Aiping Lu

Department of Medicine Faculty Papers

Xiaoqinglong granules (XQLG) has been shown to be an effective therapy in asthma animal models. We reviewed the literature and conducted this study to assess the impact of XQLG as an add-on therapy to treatment with fluticasone/salmeterol (seretide) in adult patients with mild-to-moderate, persistent asthma. A total of 178 patients were randomly assigned to receive XQLG and seretide or seretide plus placebo for 90 days. Asthma control was assessed by asthma control test (ACT), symptoms scores, FEV(1), and PEF. Baseline patient-reported Chinese medicine (CM)-specific symptoms were analyzed to determine whether the symptoms may be possible indicators of treatment response by …

Periodontal Disease Is An Independent Predictor Of Intracardiac Calcification., Gregg S Pressman, Atif Qasim, Nitin Verma, Masami Miyamae, Kumiko Arishiro, Yasuhiro Notohara, Vitalie Crudu, Vincent M. Figueredo

Division of Cardiology Faculty Papers

BACKGROUND: Periodontitis is the most common chronic inflammatory condition worldwide and is associated with incident coronary disease.

HYPOTHESIS: We hypothesized that periodontal disease would also be associated with cardiac calcification, a condition which shares many risk factors with atherosclerosis and is considered a marker of subclinical atherosclerosis.

METHODS: Cross-sectional study at two sites (USA and Japan) involving subjects with both clinical echocardiograms and detailed dental examinations. Semiquantitative scoring systems were used to assess severity of periodontal disease and echocardiographic calcification.

RESULTS: Fifty-six of 73 subjects (77%) had cardiac calcifications, and 51% had moderate to severe periodontal disease (score > 2). In …

The Complex Transcriptional Landscape Of The Anucleate Human Platelet., Paul F. Bray, Steven E. Mckenzie, Leonard Edelstein, Srikanth Nagalla, Kathleen Delgrosso, Adam Ertel, Joan Kupper, Yi Jing, Eric R. Londin, Phillipe Loher, Huang-Wen Chen, Paolo Fortina, Isidore Rigoutsos

Cardeza Foundation for Hematologic Research

BACKGROUND: Human blood platelets are essential to maintaining normal hemostasis, and platelet dysfunction often causes bleeding or thrombosis. Estimates of genome-wide platelet RNA expression using microarrays have provided insights to the platelet transcriptome but were limited by the number of known transcripts. The goal of this effort was to deep-sequence RNA from leukocyte-depleted platelets to capture the complex profile of all expressed transcripts.

RESULTS: From each of four healthy individuals we generated long RNA (≥40 nucleotides) profiles from total and ribosomal-RNA depleted RNA preparations, as well as short RNA (<40 >nucleotides) profiles. Analysis of ~1 billion reads revealed that coding …

Retro-Aortic Left Renal Vein, Joann Aichroth, Rdms, Traci B. Fox, Ms, Rt(R), Rdms, Rvt

Department of Radiologic Sciences Faculty Papers

The term retro-aortic left renal vein (RLRV) is defined as the left renal vein coursing posterior to the abdominal aorta. RLRV is an uncommon condition in which the left renal vein passes posterior to the abdominal aorta and anterior to the vertebrae. RLRV may lead to left renal vein hypertension (LRVH) syndrome, which is also known as Nutcracker syndrome. Nutcracker syndrome (NCS) is a condition in which the left renal vein is compressed causing hypertension of the vessel. RLRV and Nutcracker syndrome are vascular anomalies considered to be of clinical importance especially during surgical procedures of the renal vasculature.

Inhibitory Effect Of Il-17 On Neural Stem Cell Proliferation And Neural Cell Differentiation., Zichen Li, Ke Li, Lin Zhu, Quancheng Kan, Yaping Yan, Priyanka Kumar, Hui Xu, Abdolmohamad Rostami, Guang-Xian Zhang

Department of Neurology Faculty Papers

BACKGROUND: IL-17, a Th17 cell-derived proinflammatory molecule, has been found to play an important role in the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). While IL-17 receptor (IL-17R) is expressed in many immune-related cells, microglia, and astrocytes, it is not known whether IL-17 exerts a direct effect on neural stem cells (NSCs) and oligodendrocytes, thus inducing inflammatory demyelination in the central nervous system.

METHODS: We first detected IL-17 receptor expression in NSCs with immunostaining and real time PCR. We then cultured NSCs with IL-17 and determined NSC proliferation by neurosphere formation …

Development Of Frataxin Gene Expression Measures For The Evaluation Of Experimental Treatments In Friedreich's Ataxia., Heather L Plasterer, Eric C Deutsch, Matthew Belmonte, Elizabeth Egan, David R Lynch, James R Rusche

Department of Pediatrics Faculty Papers

BACKGROUND: Friedreich ataxia is a progressive neurodegenerative disorder caused by GAA triplet repeat expansions or point mutations in the FXN gene and, ultimately, a deficiency in the levels of functional frataxin protein. Heterozygous carriers of the expansion express approximately 50% of normal frataxin levels yet manifest no clinical symptoms, suggesting that therapeutic approaches that increase frataxin may be effective even if frataxin is raised only to carrier levels. Small molecule HDAC inhibitor compounds increase frataxin mRNA and protein levels, and have beneficial effects in animal models of FRDA.

METHODOLOGY/PRINCIPAL FINDINGS: To gather data supporting the use of frataxin as a …

Infections In Anterior Cruciate Ligament Reconstruction, C. Stucken, D.N. Garras, J.L. Shaner, Steven B. Cohen

Rothman Institute Faculty Papers

Context: Anterior cruciate ligament (ACL) reconstruction is a safe, common, and effective method of restoring stability to the knee after injury, but evolving techniques of reconstruction carry inherent risk. Infection after ACL reconstruction, while rare, carries a high morbidity potentially resulting in poor clinical outcome.

Evidence Acquisition: Data were obtained from previously published peer-reviewed literature through a search of the entire PubMed database (up to December 2012) as well as from textbook chapters.

Results: Treatment with culture-specific antibiotics and debridement with graft retention is generally more effective than graft removal, but with persistent infection consideration should be given to graft …

Vascular Endothelial Growth Factor (Vegf) Expression In Locally Advanced Prostate Cancer: Secondary Analysis Of Radiation Therapy Oncology Group (Rtog) 8610., Larry Pan, Seunghee Baek, Pamela R Edmonds, Mack Roach, Harvey Wolkov, Satish Shah, Alan Pollack, M Elizabeth Hammond, Adam P Dicker

Department of Radiation Oncology Faculty Papers

BACKGROUND: Angiogenesis is a key element in solid-tumor growth, invasion, and metastasis. VEGF is among the most potent angiogenic factor thus far detected. The aim of the present study is to explore the potential of VEGF (also known as VEGF-A) as a prognostic and predictive biomarker among men with locally advanced prostate cancer.

METHODS: The analysis was performed using patients enrolled on RTOG 8610, a phase III randomized control trial of radiation therapy alone (Arm 1) versus short-term neoadjuvant and concurrent androgen deprivation and radiation therapy (Arm 2) in men with locally advanced prostate carcinoma. Tissue samples were obtained from …

A Genome-Wide Methylation Study On Essential Hypertension In Young African American Males., Xiaoling Wang, Bonita Falkner, Haidong Zhu, Huidong Shi, Shaoyong Su, Xiaojing Xu, Ashok Kumar Sharma, Yanbin Dong, Frank Treiber, Bernard Gutin, Gregory Harshfield, Harold Snieder

Department of Medicine Faculty Papers

OBJECTIVE: There is emerging evidence from animal studies suggesting a key role for methylation in the pathogenesis of essential hypertension. However, to date, very few studies have investigated the role of methylation in the development of human hypertension, and none has taken a genome-wide approach. Based on the recent studies that highlight the involvement of inflammation in the development of hypertension, we hypothesize that changes in DNA methylation of leukocytes are involved in the pathogenesis of hypertension.

METHOD & RESULTS: We conducted a genome-wide methylation analysis on 8 hypertensive cases and 8 normotensive age-matched controls aged 14-23 years and performed …

Cis And Trans Regulatory Mechanisms Control Ap2-Mediated B Cell Receptor Endocytosis Via Select Tyrosine-Based Motifs., Kathleen Busman-Sahay, Lisa Drake, Anand Sitaram, Michael Marks, James R Drake

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Following antigen recognition, B cell receptor (BCR)-mediated endocytosis is the first step of antigen processing and presentation to CD4+ T cells, a crucial component of the initiation and control of the humoral immune response. Despite this, the molecular mechanism of BCR internalization is poorly understood. Recently, studies of activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) have shown that mutations within the BCR subunit CD79b leads to increased BCR surface expression, suggesting that CD79b may control BCR internalization. Adaptor protein 2 (AP2) is the major mediator of receptor endocytosis via clathrin-coated pits. The BCR contains five putative AP2-binding …

Cervical Assessment By Ultrasound For Preventing Preterm Delivery., Vincenzo Berghella, Jason K. Baxter Md, Mscp, Nancy W Hendrix

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Measurement of cervical length (CL) by transvaginal ultrasound (TVU) is predictive of preterm birth (PTB). It is unclear if this screening test is effective for prevention of PTB.

OBJECTIVES: To assess the effectiveness of antenatal management based on transvaginal ultrasound of cervical length (TVU CL) screening for preventing PTB.

SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2012), reviewed the reference lists of all articles and contacted experts in the field for additional and ongoing trials.

SELECTION CRITERIA: Published and unpublished randomized controlled trials including pregnant women between the gestational ages of 14 …

Skeletal Cell Differentiation Is Enhanced By Atmospheric Dielectric Barrier Discharge Plasma Treatment., Marla J Steinbeck, Natalie Chernets, Jun Zhang, Deepa S Kurpad, Gregory Fridman, Alexander Fridman, Theresa A. Freeman

Department of Orthopaedic Surgery Faculty Papers

Enhancing chondrogenic and osteogenic differentiation is of paramount importance in providing effective regenerative therapies and improving the rate of fracture healing. This study investigated the potential of non-thermal atmospheric dielectric barrier discharge plasma (NT-plasma) to enhance chondrocyte and osteoblast proliferation and differentiation. Although the exact mechanism by which NT-plasma interacts with cells is undefined, it is known that during treatment the atmosphere is ionized generating extracellular reactive oxygen and nitrogen species (ROS and RNS) and an electric field. Appropriate NT-plasma conditions were determined using lactate-dehydrogenase release, flow cytometric live/dead assay, flow cytometric cell cycle analysis, and Western blots to evaluate …