Medicine and Health Sciences Commons^™

Plasma Induced Reactive Oxygen Species-Dependent Cytotoxicity In Glioblastoma 3d Tumourspheres, Janith Wanigasekara, Carlos Barcia, Patrick J. Cullen, Brijesh Tiwari, James F. Curtin

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The aim of this study was to determine the effects of a pin‐to‐plate cold atmospheric plasma (CAP) on U‐251 MG three‐dimensional (3D) glioblastoma spheroids under different conditions. 3D tumorspheres showed higher resistance to the CAP treatment compared to 2D monolayer cells. A single CAP treatment was able to induce cytotoxicity, while multiple CAP treatments augmented this effect. CAP was also able to induce cytotoxicity throughout the tumoursphere, and we identified that reactive oxygen species(ROS) plays a major role, while H2O2plays a partial role in CAP‐induced cytotoxicity in tumour-spheres. We conclude that ROS‐dependent cytotoxicity is induced uniformly throughout glioblastoma and epidermoid …

Use And Awareness Of Heated Tobacco Products In Europe, Silvano Gallus, Alessandra Lugo, Xiaoqiu Liu, Elisa Borroni, Luke Clancy, Giuseppe Gorini, Maria José Lopez, Anna Odone, Krzysztof Przewozniak, Olena Tigova, Piet A. Van Den Brandt, Constantine Vardavas, Esteve Fernandez, Tackshs Project Investigators

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Background: Heated tobacco products (HTP) are new forms of tobacco consumption with limited information available on their use among the general population. Our objective was to analyze the prevalence and associations of use of HTP across 11 countries in Europe.

Methods: Within the TackSHS Project, in 2017-2018 we conducted a cross-sectional study with information on HTP use in the following countries: Bulgaria, England, France, Germany, Greece, Italy, Latvia, Poland, Portugal, Romania and Spain. In each country, face-to-face interviews were performed on a representative sample of around 1,000 subjects aged ≥15 years, for a total of 10,839 subjects.

Results: Overall, 27.8% …

Financial Toxicity During Breast Cancer Treatment: A Qualitative Analysis To Inform Strategies For Mitigation, Laila A. Gharzai, Kerry A. Ryan, Lauren Szczygiel, Susan Goold, Grace Li Smith, Sarah T. Hawley, John A.E. Pottow, Reshma Jagsi

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Financial toxicity from cancer treatment is a growing concern. Its impact on patients requires refining our understanding of this phenomenon. We sought to characterize patients' experiences of financial toxicity in the context of an established framework to identify knowledge gaps and strategies for mitigation. Semistructured interviews with patients with breast cancer who received financial aid from a philanthropic organization during treatment were conducted from February to May 2020. Interviews were transcribed and coded until thematic saturation was reached, and findings were contextualized within an existing financial toxicity framework. Thirty-two patients were interviewed, of whom 58% were non-Hispanic White. The mean …

A Population-Based Analysis Of Outcomes In Patients With Enteropathy-Associated T-Cell Lymphoma (Eatl), Nwabundo Anusim, Bana Antonios, Ruby Gupta, Vishal Jindal, John Khoury, Ishmael Jaiyesimi

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Background: EATL is very rare and accounts for less than 1 percent of all non-Hodgkin lymphomas. EATL occurs most commonly in patients with celiac disease and carries a uniformly poor prognosis. The optimal treatment for EATL is unclear and the data is limited to case reports and small retrospective studies.

Methods: ICD-O-3 (9717) histological code was used to identify cases of EATL from the population-based cancer registries of the Surveillance Epidemiology and End Results program (SEER) between 2006 and 2016. Frequency, demographics, and survival data were assessed using SPSS statistical software.

Results: A total of 138 cases were found. The …

Trends, Survival Outcomes, And Predictors Of Non-Adherence To Mastectomy Guidelines For Non-Metastatic Inflammatory Breast Cancer: Stage-Stratified Propensity Scoring Analysis Of Ncdb, Mohamad Sebai, Patrick Karabon, David Lee, Sayee Kiran, Nayana Dekhne

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Background/Objective: Current National Comprehensive Cancer Network (NCCN) guidelines recommend modified radical mastectomy (MRM) as the surgical treatment of choice for nonmetastatic inflammatory breast cancer (IBC). Using data from the National Cancer Database (NCDB), our study compared the national trends and outcomes of breast-conserving surgery (BCS) vs. MRM for the treatment of IBC. Methods: NCDB data from 2004 to 2014 were retrospectively analyzed. Patients’ demographics, tumor characteristics, and overall mortality (OM) trends were compared between BCS and MRM cases of IBC. Univariate, multivariate, and propensity score weighted analyses were done to compare study groups and build a predictive model for undergoing …

Gender Differences And Survival Outcomes In Breast Cancer Patients: Stage Stratified Propensity Scoring Analysis Of The National Cancer Database, M Sebai, Pe Karabon, T Luan, S Kiran, N Dekhne

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Background: There is limited research examining breast cancer gender differences. This study compares the trends and survival outcomes over the years between male (MBC) and female (FBC) breast cancer patients using the National Cancer Database (NCDB). Methods: We retrospectively analyzed the NCDB registry for MBC and FBC cases diagnosed between 2004 and 2014. Patient demographics, tumor characteristics, overall mortality (OM), and trends were compared between MBC and FBC Patients. Univariate, multivariate, and propensity score weighted analyses were done to compare MBC and FBC. Results: 19,488 MBC patients (0.9%) and 2,138,730 FBC patients (99.1%) were identified. Median follow-up was 59.63 months. …

Effect Of Hemolysis On Fourier Transform Infrared And Raman Spectra Of Blood Plasma, Dinesh Medipally, Daniel Cullen, Valérie Untereiner, Jane Bryant, Ganesh D. Sockalingum, Thi Nguyet Que Nguyen, Emma Noone, Shirley Bradshaw, Marie Finn, Mary Dunne, Aoife M. Shannon, John Armstrong, Aidan Meade, Fiona Lyng

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Hemolysis is a very common phenomenon and is referred as the release of intracellular components from red blood cells to the extracellular fluid. Hemolyzed samples are often rejected in clinics due to the interference of hemoglobin and intracellular components in laboratory measurements. Plasma and serum based vibrational spectroscopy studies are extensively applied to generate spectral biomarkers for various diseases. However, no studies have reported the effect of hemolysis in blood based vibrational spectroscopy studies. This study was undertaken to evaluate the effect of hemolysis on infrared and Raman spectra of blood plasma. In this study, prostate cancer plasma samples (n …

Pre-Clinical Models Of Small Cell Lung Cancer And The Validation Of Therapeutic Targets, Jane S.Y. Sui, Petra Martin, Steven G. Gray

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Introduction: Small-cell lung cancer (SCLC) is an aggressive form of lung cancer that has a dismal prognosis. One of the factors hindering therapeutic developments for SCLC is that most SCLC is not surgically resected resulting in a paucity of material for analysis. To address this, significant efforts have been made by investigators to develop pre-clinical models of SCLC allowing for downstream target identification in this difficult to treat cancer.

Areas covered: In this review, we describe the current pre-clinical models that have been developed to interrogate SCLC, and outline the benefits and limitations associated with each. Using examples …

High Lymph Node Positive To Sampled Ratio As A Potential Indication For Postoperative Radiation Therapy In Patients With Pn2 Non-Small-Cell Lung Cancer, Nikhil P Mankuzhy, Muayad F Almahariq, Craig W Stevens, Thomas J Quinn

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Background: The role for postoperative radiation therapy (PORT) for patients with non–small-cell lung cancer (NSCLC) with mediastinal lymph node (LN) involvement (pN2 disease) is controversial. We performed a SEER analysis comparing surgery alone with PORT among patients with pN2 NSCLC. As we await the final results of the LUNG ART trial, a subset of patients with a high LN positive to sampled (LPR) ratio may benefit from PORT. Patients/methods: Patients with pN2 NSCLC, ranging from 1989-2016, were assessed from the Surveillance, Epidemiology and End Results (SEER) database. A propensity score (PS)-matched, inverse probability of treatment weighting (IPTW) analysis was conducted …

Recent Advances In The Vibrational Spectroscopic Diagnosis Of Non-Small Cell Lung Cancer, Declan O'Dea, Fiona Lyng, Siobhan Nicholson, Finbar O'Connell, Aoife Maguire, Alison Malkin

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Lung cancer is the leading cause of cancer deaths worldwide accounting for 1.69 million deaths in 2015. Studies have indicated a 5 year survival rate of 8%–15% in western countries, although a survival rate as low as 1% has been demonstrated for late stage diagnosis. With the advent of targeted therapies, it is imperative to accurately differentiate non-small cell lung cancer (NSCLC) subtypes in order to ensure efficacy of treatment for patients. Immunohistochemistry and molecular techniques for the diagnosis of NSCLC are increasingly part of the diagnostic algorithm and clinical work-up of lung cancer patients, however due to the limitation …

Subjective And Objective Assessment Of Taste And Smell Sensation In Advanced Cancer, Niamh Mcgettigan, Pauline Uí Dhuibhir, Michelle Barrett, Jessica Sui, Lucy Balding, Stephen Higgins, Norma O'Leary, Aileen Kennedy, Declan Walsh

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Context: Taste and smell abnormalities (TSA) occur throughout the cancer trajectory regardless of cancer primary site and contribute to cancer-associated malnutrition. TSA etiology is poorly understood. Tumor-related inflammation is a possible cause. Objective: This study examined the prevalence, characteristics, and severity of TSA in advanced cancer and explored the relationship between TSA and nutritional status. No previous study combined subjective and objective measures for both taste and smell assessment in this population. Method: Consecutive advanced cancer hospice patients were recruited. A modified version of the “Taste and Smell Survey” assessed subjective TSA. Validated taste strips and “Sniffin’ …

Effect Of Neoadjuvant Chemoradiation On Preoperative Pulmonary Physiology, Postoperative Respiratory Complications And Quality Of Life In Patients With Oesophageal Cancer, J. A. Elliott, L. O'Byrne, G. Foley, C. F. Murphy, Suzanne Doyle, S. King, E. M. Guinan, N. Ravi, V. Reynolds

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Background: It remains controversial whether neoadjuvant chemoradiation (nCRT) for oesophageal cancer influences operative morbidity, in particular pulmonary, and quality of life. This study combined clinical outcome data with systematic evaluation of pulmonary physiology to determine the impact of nCRT on pulmonary physiology and clinical outcomes in locally advanced oesophageal cancer.

Methods: Consecutive patients treated between 2010 and 2016 were included. Three-dimensional conformal radiation was standard, with a lung dose–volume histogram of V20 less than 25 per cent, and total radiation between 40 and 41⋅4Gy. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity …

A Custom Radiopaque Thermoresponsive Chemotherapy-Loaded Hydrogel For Intratumoural Injection: An In Vitro And Ex Vivo Assessment Of Imaging Characteristics And Material Properties, Seóna M. Rossi, Timothy E. Murray, John Cassidy, Michael J. Lee, Helena M. Kelly

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Purpose Thermoresponsive hydrogels are gels which have different properties at varying temperatures. The objective of this study was to assess the material characteristics, imaging properties and chemotherapeutic drug release profile of a novel radiopaque thermoresponsive hydrogel in vitro, which is liquid at room temperature but solidifies at body temperature, to determine potential suitability for intratumoural delivery. Materials and Methods An iodinated radiopaque thermoresponsive hydrogel was formulated using iodixanol at a range of concentrations and assessed for sol–gel transition, radiopacity and imaging using CT and US. A lead formulation containing iodixanol at a concentration of 9.22% weight by weight (w/w, g …

Patient Experiences Of A Physiotherapy-Led Multidisciplinary Rehabilitative Intervention After Successful Treatment For Oesophago-Gastric Cancer, Annemarie Bennett, L. O'Neill, D. Connolly, E. M. Guinan, L. Boland, Suzanne Doyle, J. O'Sullivan, J. V. Reynolds, J. Hussey

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Purpose To qualitatively explore the perceived impact of a 12-week rehabilitative intervention for oesophago-gastric cancer survivors on their physical, mental and social wellbeing. Methods Of the 21 participants who completed the intervention, 19 took part in a semi-structured focus group interview. Four audio-taped focus groups were held, ranging in size from two to eight participants. Focus groups were transcribed and analysed using a descriptive qualitative approach. Results At recruitment, participants were 23.5 ± 15.2 months post-surgery and all had suboptimal fitness levels. Participants reported improvements in their physical capacity and ability to carry out activities of daily living during the …

Sarcopenia During Neoadjuvant Therapy For Oesophageal Cancer: Characterising The Impact On Muscle Strength And Physical Performance, E.M. Guinan, Suzanne Doyle, A.E. Bennett, L. O'Neill, J. Gannon, J.A. Elliott, J. O'Sullivan, J.V. Reynolds, J. Hussey

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Purpose Preoperative chemo(radio)therapy for oesophageal cancer (OC) may have an attritional impact on body composition and functional status, impacting postoperative outcome. Physical decline with skeletal muscle loss has not been previously characterised in OC and may be amenable to physical rehabilitation. This study characterises skeletal muscle mass and physical performance from diagnosis to post-neoadjuvant therapy in patients undergoing preoperative chemo(radio)therapy for OC.

Methods Measures of body composition (axial computerised tomography), muscle strength (handgrip), functional capacity (walking distance), anthropometry (weight, height and waist circumference), physical activity, quality-of-life and nutritional status were captured prospectively. Sarcopenia status was defined as pre-sarcopenic (low muscle …

Carcinogenesis In Prostate Cancer: The Role Of Long Non-Coding Rnas, John Aird, Anne-Marie Baird, Marvin C.J Lim, Ray Mcdermott, Stephen P. Finn, Steven G. Gray

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LncRNAs appear to play a considerable role in tumourigenesis through regulating key processes in cancer cells such as proliferative signalling, replicative immortality, invasion and metastasis, evasion of growth suppressors, induction of angiogenesis and resistance to apoptosis. LncRNAs have been reported to play a role in prostate cancer, particularly in regulating the androgen receptor signalling pathway. In this review article, we summarise the role of 34 lncRNAs in prostate cancer with a particular focus on their role in the androgen receptor signalling pathway and the epithelial to mesenchymal transition pathway.

Biofunctionalized Capillary Flow Channel Platform Integrated With 3d Nanostructured Matrix To Capture Circulating Tumor Cells, Shashwat Banerjee, Ganesh Khutale, Vrushali Khobragade, Narendra Kale, Milind Pore, Govind Chate, Archana Jalota-Badhwar, Manoj Dongare, Jayant Khandare

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Circulating tumor cells (CTCs) from peripheral blood account genetic information for cancer diagnosis and overall disease monitoring. Analysis of “liquid biopsy” holds immense promise as it may lead to new approaches for cancer treatment. The study reports effective and continuous flow microchannel system for isolating CTCs using transferrin conjugated 3D matrix synthesized by crosslinking polyethylene glycol-Fe3O4 nanostructures for rapid and efficient capturing of CTCs. The platform provides option of using multiple microchannel units in series that can influence higher cell-capture efficiency due to increasing cell-substrate contact frequency. CTCs are captured with high efficiency even at low concentration of target cells …

The "Eyes" Have It?-Intra- And Inter-Observer Reproducibility Of The Pd-L1 Companion Diagnostic Assay, Steven G. Gray, Mark Wright, Stephen Finn

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No abstract available.

Methodologies And Considerations For Bladder Cancer Detection With Raman Based Urine Cytology, Laura T. Kerr, Thérése M. Lynn, Ivor M. Cullen, Padraig J. Daly, Nigam Shah, Shirley O'Dea, Alison Malkin, Bryan M. Hennelly

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Bladder cancer has the highest recurrence rate of any cancer. The American Urological Association recommends cystoscopic surveillance every 3–6 months for 3 years, and at least once a year thereafter, particularly for high-risk patients; however, cystoscopy is invasive, expensive, and is not without insignificant morbidity for the patient. Urine cytology is often used as an adjunct to cystoscopy; however, it has a low sensitivity in detecting low grade bladder cancers. Recent studies have investigated the application of Raman micro-spectroscopy for the detection of bladder cancer via urine cytology, and it has been demonstrated to significantly improve the diagnostic sensitivity of …

Parallel Profiles Of Inflammatory And Effector Memory T Cells In Visceral Fat And Liver Of Obesity-Associated Cancer Patients, Melissa Conroy, Karen Galvin, Suzanne Doyle, Maria Kavanagh, Ann-Marie Mongan, Aoife Cannon, Gillian Moore, John Reynolds, Joanne Lysaght

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In the midst of a worsening obesity epidemic, the incidence of obesity-associated morbidities, including cancer, diabetes, cardiac and liver disease is increasing. Insights into mechanisms underlying pathological obesity-associated inflammation are lacking. Both the omentum, the principal component of visceral fat, and liver of obese individuals are sites of excessive inflammation, but to date the T cell profiles of both compartments have not been assessed or compared in a patient cohort with obesity-associated disease. We have previously identified that omentum is enriched with inflammatory cytokines, chemokines and T cells. Here, we compared the inflammatory profile of T cells in the omentum …

Long-Term Financial Burden Of Breast Cancer: Experiences Of A Diverse Cohort Of Survivors Identified Through Population-Based Registries, Reshma Jagsi, John A.E. Pottow, Kent A. Griffith, Cathy Bradley, Ann S. Hamilton, John Graff Rutgers University, Steven J. Katz, Sarah T. Hawley

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Purpose: To evaluate the financial experiences of a racially and ethnically diverse cohort of long-term breast cancer survivors (17% African American, 40% Latina) identified through population-based registries. Methods: Longitudinal study of women diagnosed with nonmetastatic breast cancer in 2005 to 2007 and reported to the SEER registries of metropolitan Los Angeles and Detroit. We surveyed 3,133 women approximately 9 months after diagnosis and 4 years later. Multivariable models evaluated correlates of self-reported decline in financial status attributed to breast cancer and of experiencing at least one type of privation (economically motivated treatment nonadherence and broader hardships related to medical expenses). …

Cell Death Pathways In Directly Irradiated Cells And Cells Exposed To Medium From Irradiated Cells, K.K. Jella, Amaya Garcia, Brendan Mcclean, Hugh Byrne, Fiona Lyng

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Purpose: The aim of this study was to compare levels of apoptosis, necrosis, mitotic cell death and senescence after treatment with both direct radiation and irradiated cell conditioned medium. Materials and methods: Human keratinocytes (HaCaT cell line) were irradiated (0.005, 0.05 and 0.5 Gy) using a cobalt 60 teletherapy unit. For bystander experiments, the medium was harvested from donor HaCaT cells one hour after irradiation and transferred to recipient HaCaT cells. Clonogenic assay, apoptosis, necrosis, mitotic cell death, senescence and cell cycle analysis were measured in both directly irradiated cells and bystander cells Results: A reduction in cell survival was …

The Effect Of Genetic Background And Dose On Non-Targeted Effects Of Radiation, Sarah Irons, Virginia Sierra, Deborah Bowler, Kim Chapman, Stefania Militi, Fiona Lyng, Munira Kadhim

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Purpose: This work investigates the hypothesis that genetic background plays a significant role in the signalling mechanisms underlying induction and perpetuation of genomic instability following radiation exposure.

Materials and methods: Bone marrow from two strains of mice (CBA and C57) were exposed to a range of X-ray doses (0, 0.01, 0.1, 1 and 3 Gy). Different cellular signalling endpoints: Apoptosis, cytokine levels and calcium flux, were evaluated at 2 h, 24 h and 7 d post-irradiation to assess immediate and delayed effects.

Results: In CBA (radiosensitive) elevated apoptosis levels were observed at 24 h post X-irradiation, and …

Brief Report: A Phase Ii "Window-Of-Opportunity" Frontline Study Of The Mtor Inhibitor, Temsirolimus Given As A Single Agent In Patients With Advanced Nsclc, An Ncctg Study, Nicholas F. Reuter Md

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BACKGROUND:

In an effort to evaluate the single agent activity of temsirolimus in previously untreated non-small-cell lung cancer, the North Central Cancer Treatment Group undertook a frontline "window-of-opportunity" study.

METHODS:

Patients received 25 mg of temsirolimus administered intravenously as a weekly 30 minute infusion, on a 4-week cycle. Based on a two-stage Fleming design, the treatment would be promising if at least four of the first 25 evaluable patients in stage I or at least six of the 50 evaluable patients at the end of stage II have a confirmed response. Fresh tumor biopsies were obtained to evaluate predictive markers …

Malpractice Suits And Physician Apologies In Cancer Care, Eugene Chung, Jill R. Horwitz, John A.E. Pottow, Reshma Jagsi

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Conside the following case: The patient is a 44-year-old woman who presents for radiation treatment of an isolated locoregional recurrence of breat cancer in her chest wall, 3 years after undergoing masectomy. At the time of diagnosis, she had T2N2M0 disease, with four of 15 lymph nodes involved with tumor. She received a masectomy with negative margins and appropriate chemotherapy, but none of her physicians talked to her about postmasectomy radiation therapy, which would clearly have been indicated to reduce her risk of locoregional failure and would have been expected to improve her likelihood of survival. She asks the radiation …

Differential Genome-Wide Array–Based Methylation Profiles In Prognostic Subsets Of Chronic Lymphocytic Leukemia, Meena Kanduri, Nicola Cahill, Hanna Göransson, Camilla Enström, Fergus Ryan, Anders Isaksson, Richard Rosenquist

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Global hypomethylation and regional hypermethylation are well-known epigenetic features of cancer; however, in chronic lymphocytic leukemia (CLL), studies on genome-wide epigenetic modifications are limited. Here, we analyzed the global methylation profiles in CLL, by applying high-resolution methylation microarrays (27 578 CpG sites) to 23 CLL samples, belonging to the immunoglobulin heavy-chain variable (IGHV) mutated (favorable) and IGHV unmutated/IGHV3-21 (poor-prognostic) subsets. Overall, results demonstrated significant differences in methylation patterns between these subgroups. Specifically, in IGHV unmutated CLL, we identified methylation of 7 known or candidate tumor suppressor genes (eg, VHL, ABI3, and IGSF4) as well as 8 unmethylated genes involved in …

Adenovirus E4orf4 Induces Hpv-16 Late L1 Mrna Production, Monica Somberg, Margaret Rush, Joanna Fay, Fergus Ryan, Helen Lambkin, Göran Akusjärvi, Stefan Schwartz

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The adenovirus E4orf4 protein regulates the switch from early to late gene expression during the adenoviral replication cycle. Here we report that overexpression of adenovirus E4orf4 induces human papillomavirus type 16 (HPV-16) late gene expression from subgenomic expression plasmids. E4orf4 specifically overcomes the negative effects of two splicing silencers at the two late HPV-16 splice sites SD3632 and SA5639. This results in the production of HPV-16 spliced L1 mRNAs. We show that the interaction of E4orf4 with protein phosphatase 2A (PP2A) is necessary for induction of HPV-16 late gene expression. Also an E4orf4 mutant that fails to bind the cellular …

Lupus Anticoagulunt Associated With Transient Severe Factor X Deficiency: A Report Of Two Patients Presenting With Major Bleeding Complications, Aneel A. Ashrani, Agnes Aysola, Hani Al-Khatib Md, William L. Nichols

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Abstract

Acquired factor X (FX) deficiency is rare, but has been reported in diverse disease states, including systemic amyloidosis and respiratory infections. FX deficiency associated with lupus anticoagulant (LA) and a bleeding diathesis has not been previously reported. We report two patients both of whom presented with a severe bleeding diathesis after a preceding respiratory infection due to isolated FX deficiency associated with a LA. The FX deficiency and LA were transient. We conclude that patients with LA may rarely present with severe acquired FX deficiency. This may be another mechanism whereby patients with antiphospholipid antibodies present with bleeding complications.