tbuckley/cabot-search huggingface dataset:
S74 Incidence and Analysis of Risk Factors For Thrombocytopenia in Critically Ill Patients
Authors: LK Gupta, B James
Journal: Thorax (2012)

<h3>Introduction</h3> Thrombocytopenia occurs in 15% to 58% of intensive care unit patients. Up to 25% of acutely ill patients develop drug-induced thrombocytopenia. Establishing the etiology of secondary thrombocytopenia is challenging, since many medications and co morbidities have been implicated. <h3>Objective</h3> To define the incidence and severity of thrombocytopenia in critically ill patients and to examine risk factors that may be related to the development of thrombocytopenia. <h3>Method</h3> This is a retrospective chart review of 328 critically ill patients with thrombocytopenia requiring at least 72 hours of critical care. 30 suspected risk factors, including patient characteristics, drug effects, and associated diseases were identified from the literature and further evaluated using a multiple logistic regression. Mild Thrombocytopenia defined as platelet count less than 200 x 10(9)/L was observed frequently, but only 9 percent had severe thrombocytopenia defined as less than 20 x 10(9)/L. <h3>Results</h3> Demographic characteristics of patients predisposed to thrombocytopenia are males, older than 55, and Hispanic population. Hemodynamic instability and/or heparin exposure appear to be the strongest identifiable correlates with thrombocytopenia. Sepsis, acute kidney injury and respiratory failure were strongly correlated (p&lt;0.0001) with thrombocytopenia. Patients with severe thrombocytopenia were found to have concurrent alterations in liver function tests. Patients with central line placement and heparin exposure were associated strongly with mild thrombocytopenia (p&lt;0.0001). Drug therapies that were correlated with thrombocytopenia included Heparin, Protonix, Lasix, Ativan and Zofran and antibiotics such as Vancomycin, Cephalosporins and Levaquin. <h3>Conclusion</h3> Drug regimens should be evaluated daily for minimization of adverse drug events including thrombocytopenia. Once the diagnosis is suspected, clinicians should identify the medication and/or risk factors causing secondary thrombocytopenia to assess the timeline of development. Co morbidity associated with thrombocytopenia was sepsis syndrome, liver disorder, alcoholism and atrial fibrillation. Medications commonly associated with drug-induced thrombocytopenia include glycoprotein IIb/IIIa inhibitors, cinchona alkaloids, antibiotics, anticonvulsants, and heparin. Thrombocytopenia generally resolved in most patients with critical management of the disease and discontinuation of the offending medication.
Vesicocecal Fistula Detected During Dynamic Renal Scintigraphy
Authors: George Panoutsopoulos, Ioannis Ilias, Vassilios Yiannakopoulos
Journal: Clinical Nuclear Medicine (2000)

Vesicocecal fistulas are uncommon, and occur mainly as complications of diverticular disease and rarely of appendicitis. The authors describe a 45-year-old woman in whom a right hypoplastic kidney was found during the diagnostic work-up for anemia. Tc-99m DTPA dynamic renal imaging was performed to assess the patient’s renal function in light of a right nephrectomy. After voiding, Tc-99m DTPA was noted to flow into the colon. A vesicocecal fistula was subsequently diagnosed and was surgically treated. The present report stresses the importance of obtaining postvoiding views when renal imaging is viewed.
Abstract 2113: Elucidating mechanisms of regulation of homologous recombination utilizing a PALB2 fusion protein that contains the BRCT repeats of BRCA1
Authors: Fan Zhang, Gregory Bick, Paul R. Andreassen
Journal: Cancer Research (2012)

Abstract The products of the breast cancer susceptibility genes, BRCA1 and PALB2, directly interact through coiled-coil domains present in each protein. How PALB2 is recruited to sites of DNA damage and how the BRCA1-PALB2 interaction regulates the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) have remained unclear, however. Here, the BRCT repeats of BRCA1, which are required for its localization, were fused to a PALB2 mutant incapable of binding BRCA1. We introduced this fusion protein into HCC1937 breast cancer cells that contain a truncated BRCA1 or into cells in which full-length BRCA1 was depleted using a siRNA. The fusion protein corrected the deficiency for PALB2 foci in both systems, either with or without exposure to ionizing radiation. Importantly, expression of the fusion protein also corrected a defect in PALB2-dependent assembly of foci by the RAD51 recombinase. Further, we also introduced the fusion protein into PALB2/FANCN-deficient cells from a Fanconi anemia patient. The fusion protein restored both PALB2 and RAD51 foci in these cells without binding to BRCA1. Strikingly, the fusion protein also conferred resistance to mitomycin C (MMC) and corrected a defect in DSB-initiated HR in PALB2-deficient cells. Our data convincingly demonstrate that BRCA1 localizes PALB2 to sites of DNA damage, and that this is necessary for recruitment of RAD51 and for HR. Contrary to a published report, since the fusion protein is incapable of binding to PALB2, our results suggest that PALB2 functions, such as HR, are mediated by the BRCA1-PALB2 interaction rather than the PALB2-PALB2 dimer. Given that BRCA1 and PALB2 participate in a pathway of DNA repair by HR, our results suggest that mutations which disrupt the BRCA1-PALB2 interaction may lead to the genetic instability that underlies the development of cancer. Additionally, the BRCA1-PALB2 interaction may be a potential therapeutic target for sensitization of cancer cells to DNA damaging agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2113. doi:1538-7445.AM2012-2113
Meningeal carcinomatosis in patients with breast cancer: clinical features and prognostic factors in 91 patients from a single institution.
Authors: H Gautier, M Guilhaume, FC Bidard, VC Dieras, J Pierga, A Livartowski, L Mignot
Journal: Cancer Research (2009)

Abstract Abstract #1090 Background&amp;#x2028; Breast cancer is the leading solid tumor responsible for meningeal carcinomatosis (MC) and the incidence is rising. To date, there is no standard of care and few prospective trials. Intrathecal treatment is provided but the modalities remain controversial.&amp;#x2028; Methods&amp;#x2028; From our data base we recorded 91 patients with breast MC admitted to Institut Curie between 2000-2007. Lumbar punction was performed in all patients for cerebrospinal fluid (CSF) cytology, protein level and dosage of CYFRA 21. Intra-thecal treatment: methotrexate 15 mg day1 to 5 and hydrocortisone acetate day 1 with oral folinic acid rescue day 1 to 5 every two weeks.&amp;#x2028; Results&amp;#x2028; Median age was 53 years (range 30-78). Tumor type was ductal carcinoma (63%), lobular (28%), ER positive 74%, HER2 overexpressed 10% and triple negative 31%. All patients presented other metastatic site: bone (67%), liver (42%) lung (29%), brain (38%). The median interval between primary tumor and diagnosis of MC was 60 months.&amp;#x2028; Amongst the 80 patients treated (87%) with intra-thecal MTX, clinical response was observed in 88% of cases. There was a strong correlation between clinical response and survival (p&amp;lt;0.001). Normalization of cerebrospinal fluid cytology (CSFC) was observed in 13 % of patients and was associated with better survival: 13 months versus 2 months (p=0.003). Improvement of other biologic parameters as CSF protein and CYFRA 21 was observed in 17% and 80% of patients respectively. The median survival was 4.5 months (0-53). In multivariate analysis, prognostic factors were: performance status 3-4 (p&amp;lt;0.0001), more than 3 chemotherapy regimens before MC diagnosis (p=0.04), lack of ER (p=0.04) and high CYFRA 21 at diagnosis (p=0.01). With these factors a prognostic score may select patients with a true benefit to IT MTX (20% survival &amp;gt; 1 year) or patients for whom treatment will have no impact on survival (&amp;lt; 3 months).&amp;#x2028; Conclusion: This score has to be confirmed in prospective study and new modalities of treatments need to be evaluated according to the biology of disease. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1090.
Drainages d'abcès pelviens par échoendoscopie thérapeutique: étude rétrospective d'une série consécutive de 14 patients
Authors: L Poincloux, P Guibert, O Rouquette, E Buc, D Pezet, G Bommelaer
Journal: Endoscopy (2012)

Le but de cette étude était d'évaluer l'efficacité et la morbidité des drainages trans-rectaux d'abcès pelviens réalisés par écho-endoscopie thérapeutique à partir d'une série rétrospective monocentrique.
LOW COMPLIANCE OF IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR USE FOR HEART FAILURE WITH REDUCED EJECTION FRACTION IN AN UNDERSERVED POPULATION
Authors: Yifan Lu, Ningxin Wan, The Hung Nguyen, Nidhi Madan, Ninel Hovnanians, Juan Carlos Ruiz Diaz, Luise Holzhauser, Michael Grushko, Robert Faillace
Journal: Journal of the American College of Cardiology (2016)
Abstract 687: Enhanced expression of multidrug resistance (<i>MDR</i>) protein in malignant pleural mesothelioma (MPM) patients is possibly achieved via <i>Osteoponin, CD44</i> variants and <i>p-AKT</i> expression
Authors: Abeer A. Bahnassy, Abdel-Rahman N. Zekri, Salem Eid, Abdel-Rahman M. Abdel-Rahman, Moustafa R. Mahmoud, Rabab M. Gaafar
Journal: Cancer Research (2011)

Abstract Malignant pleural mesothelioma (MPM) is an aggressive disease, which is discovered late. It is resistant to chemotherapy and thus shows a dismal prognosis. Recently, in vitro studies demonstrated that osteoponin (is involved in the development of MPM via induction of multidrug resistance through unidentified mechanism(s). Tissue and serum samples from 55 Egyptian cases of MPM were assessed for OPN, MDR, p-AKT and CD44 proteins and RNA by ELISA, immunohistochemistry (IHC) and RT-PCR. Normal pleural samples (20) were used as a control. Results were correlated with standard prognostic factors and survival. In tissues, OPN, CD44, MDR and p-AKT protein overexpression was detected in 39, 26, 37 and 25 cases; respectively whereas RNA expression was reported in 31, 24, 30, 24 cases; respectively. In sera, OPN, CD44, MDR and p-AKT proteins were found in 36, 20, 40, 28 cases; respectively. There was a significant correlation between OPN expression and other markers, at the protein and RNA levels (p&amp;lt;0.05). The concordance between OPN and MDR expression was the highest (98%). Control samples were negative for the studied markers except for 4 cases that showed faint focal expression of p-AKT and CD44 proteins. OS was significantly associated with performance status, increased expression of OPN, MDR and CD44 in univariate and multivariate analysis (p&amp;lt;0.01). A borderline significance was reported between poor response to treatment and increased expression of OPN, CD44, MDR either singly (p=0.063) or combined (p=0.045) In conclusion, OPN, CD44, and p-AKT could be used as poor prognostic markers in MPM being associated with reduced OS rates and poor response to treatment. This could be achieved via enhanced MDR expression with subsequent resistance to chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 687. doi:10.1158/1538-7445.AM2011-687
1240 A FUNCTIONAL ROLE OF MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) FOR FATTY LIVER DISEASE AND OBESITY IN MICE
Authors: D. Heinrichs, M. Knauel, A. Nellen, C. Trautwein, R. Bucala, J. Bernhagen, H.E. Wasmuth
Journal: Journal of Hepatology (2012)
Abstract 1106: Mechanism for activation of mutated EGF receptors in lung cancer.
Authors: Monica L. Red Brewer, Darson Lai, Mark A. Lemmon, William Pao
Journal: Cancer Research (2013)

Abstract Previous studies have demonstrated that wild-type (WT) EGFRs are activated by an allosteric mechanism in which a ‘donor’ tyrosine kinase domain (TKD) monomer contacts an ‘acceptor’ TKD monomer, leading to its activation. Here, we present biochemical reconstitution data demonstrating that receptor activation by the most frequently occurring EGFR mutations found in lung cancer does not adhere to this mechanism. Mutated EGFRs hyperphosphorylate their WT counterparts and appear to adopt a conformation that allows them to function as acceptors but not as donors to WT EGFR. As acceptors, the mutated EGFRs also show enhanced association with WT EGFR. We suggest the term “superacceptor activity” to describe this directionally-limited mutant-specific mechanism of EGFR transactivation. Mutated EGFRs also hyperphosphorylate the related ErbB family member, ErbB-2, in a similar manner. Collectively, these data provide insights into a mechanism for activation of lung cancer-associated mutant EGFRs. Since WT EGFRs are usually present in EGFR mutant tumor cells, our studies additionally argue that WT EGFRs contribute to tumorigenesis and may alter sensitivity to EGFR-targeted therapy. Citation Format: Monica L. Red Brewer, Darson Lai, Mark A. Lemmon, William Pao. Mechanism for activation of mutated EGF receptors in lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1106. doi:10.1158/1538-7445.AM2013-1106
Intracranial Arteriovenous Malformation
Authors: Amadeo R Rodriguez, Ramiro Larrazabal
Journal: New England Journal of Medicine (2015)

A 28-year-old man with a childhood history of spontaneous intracranial hemorrhage presented with seizures and loss of consciousness. Ophthalmoscopic examination revealed a retinal arteriovenous malformation in the right eye; the left eye was normal.
Abstract 2988: Regulation of mitosis and taxane response by Daxx
Authors: Serena Giovinazzi, Cory Lindsay, Viacheslav Morozov, Hyo Han, Alexander Ishov
Journal: Cancer Research (2011)

Abstract Current theories suggest that mitotic proteins are essential for cellular response to taxanes (paclitaxel and docetaxel), a widely-used family of chemotherapeutic compounds. We found that absence or depletion of protein Daxx increases cellular resistance to paclitaxel _a common trait of patients diagnosed with breast cancer and other malignancies. Particularly, we observed that 1) paclitaxel induced cell death, in both human breast cancer and mouse cell lines, depends on the level of Daxx; 2) cells become paclitaxel-resistant upon experimental depletion of Daxx; 3) breast cancer specimens accumulate differential level of Daxx; 4) docetaxel response in breast cancer patients correlates with level of Daxx mRNA. We also found that Daxx is important for the proper progression of mitosis in human cells: duration of mitotic stages is altered in cells stably depleted of Daxx which also show increased stability of cyclin B1. Thus, protein Daxx, that was previously characterized as a transcription repressor and an apoptotic-related protein, may also have a novel function in mitosis progression as a prometaphase checkpoint release protein in control conditions and upon mitotic stress. In order to understand the mechanism by which Daxx orchestrates mitosis progression and identify new potential targets responsible for taxane resistance, we adopted a functional proteomic approach to identify Daxx-associated mitotic complex. We optimized the protocol for Tag based affinity purification in a way to obtain Daxx expressed downstream of FLAG Tag in tandem with HA Tag (FH) and a Thrombin Cleavage Site (TCS). HEp2 cells transduced with pOZ-FH-TCS-Daxx and the empty pOZ-FH plasmid (control), synchronized by double thymidine block and next arrested in pro-metaphase with paclitaxel, were used to purify Daxx containing mitotic complex. Mitotic specific Daxx interacting proteins were identified by SDS-PAGE followed by mass spectrometry. The functional characterization of newly identified Daxx mitotic partners will shed lights on the complex mechanism/phenomena of taxanes resistance and ultimately offer the molecular basis for successful treatment strategies of breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2988. doi:10.1158/1538-7445.AM2011-2988
P752 GENETIC POLYMORPHISM IN PNPLA3 GENE IMPACTS DISEASE PROGRESSION AND HEPATOCELLULAR CARCINOMA DEVELOPMENT IN CHRONIC HEPATITIS C
Authors: M. Kurosaki, K. Tsuchiya, Y. Yasui, N. Tamaki, S. Matsuda, K. Hattori, N. Izumi
Journal: Journal of Hepatology (2014)
FRI0543 Is baseline disease activity associated with 1-year health care costs &amp; productivity losses after biologic treatment start in patients with ra?
Authors: K. Johansson, J. K. Eriksson, H. Miller, R. F. van Vollenhoven, J. Askling, M. Neovius
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Little is known about the cost trajectory in patients starting biologics with moderate disease activity. <h3>Objectives</h3> To compare 1-year health care costs and productivity losses after initiation of first biologic treatment in RA-patients with high vs moderate disease activity at treatment start. <h3>Methods</h3> In the Swedish Biologics Register (ARTIS), we identified patients with RA starting their first biologic in 2007-2009 who had baseline DAS28 recorded (n=2143; 138 low [DAS28 &lt;3.2], 898 moderate [DAS28 3.2-5.0], and 1107 high disease activity [DAS28 ≥5.1]). Data on inpatient and nonprimary outpatient care, prescription drugs, and productivity losses were retrieved from nationwide registers. Mean cost differences (expressed in 2010 €) with 95%CIs were estimated using nonparametric bootstrapping, adjusting for age, sex, and costs during the previous year. <h3>Results</h3> Patients with high baseline disease activity were older than those with moderate disease activity (59 vs 56y; P&lt;.001), but did not differ regarding sex (75% vs 75% women; P=.99) or disease duration (10 vs 9y; P=.14). 64% of patients with high and 75% with moderate disease activity were of working age (18-64y; P&lt;.001). During the year after initiation of biologics, patients starting with high and moderate disease activity accumulated health care costs of €17,993 and €16,488, respectively (adj. difference €965, 95%CI 2-1951). In working age patients, high (vs moderate) baseline disease activity was associated with greater productivity losses (€23,837 vs €18,394; adj. difference €1550, 95%CI 538-2562). For patients starting biologics with high compared to moderate disease activity the total 1-year costs were €41,089 vs €34,416 (Figure; adj. difference €2079, 95%CI 586-3572). <h3>Image/graph</h3> <h3>Conclusions</h3> Patients initiating biologic treatment with high compared to moderate baseline disease activity accumulated more costs over 1 year. After adjustment, the costs were higher for inpatient care and productivity losses, but not for nonprimary outpatient care or drugs. <h3>Acknowledgements</h3> The study was partly funded by Pfizer. <h3>Disclosure of Interest</h3> None Declared
Abstract 1084: Honokiol induces G1 phase cell cycle arrest in human epidermoid carcinoma A431 cells
Authors: Ruth F. Guillermo, Shivani Chilampalli, Gudiseva Chandrasekhar, Radhey S. Kaushik, Hesham Fahmy, Chandradhar Dwivedi
Journal: Cancer Research (2010)

Abstract Recent studies from our laboratory have indicated that pre applications of honokiol (one hour before) prevent UVB- induced skin cancer development in female SKH-1 mice. Honokiol reduced significantly the cell viability of A431, as assessed by MTT (IC50 60 μM) and BrdU incorporation assay. The aim of this study is to investigate the effects of honokiol on the cell cycle of human epidermoid carcinoma A431 cell line and to investigate the influence of honokiol in the A431 cell cycle regulator proteins expression. A431 cells were treated at different concentrations with honokiol for specified periods of time (8, 16, 24, 32, 40 and 48 hours). Cells were harvested and fixed in 70% ethanol and stored at −20 °C. The cell cycle phase analysis was performed by using a Beckton Dickinson Facstar flow cytometer and CellQuest software. Cell lysates were prepared from A431 cells treated with honokiol in similar conditions; proteins were analyzed by Western blotting. Treatment with honokiol at concentration 50 μM and time periods of 24, 32, 40 and 48 hours blocked the A431 cell cycle in G1 phase significantly (P&amp;lt;0.05) and decreased the percentage of cells in the S and G2/M phase. Honokiol affects the expression of proteins involved in the A431 cell cycle regulation, down-regulating the expression of cyclin A, CDK2, CDK4 and CDK6 proteins and up-regulating the expression of p21 and p27 proteins which are CDKs inhibitors. These findings indicate that honokiol causes cell cycle arrest at G1 phase and alteres the expression of various proteins involved in the G1 phase of A431 cell cycle. (Supported by Translational Cancer Center Research Grant, funded as 2010 Research Initiative Center by the State of South Dakota). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1084.
P1027 IS THE ELF-SCORE A VALID SUBSTITUTION FOR HVPG TO DETECT CLINICALLY SIGNIFICANT PORTAL HYPERTENSION (CSPH) NON-INVASIVELY?
Authors: S. Hametner, A. Ferlitsch, A. Etschmaier, M. Ferlitsch, R. Schöfl, A. Ziachehabi, D. Trubert-Exinger, A. Maieron
Journal: Journal of Hepatology (2014)
Nighttime Light Studied as Possible Breast Cancer Risk
Authors: J. Waalen
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Nighttime Light Studied as Possible Breast Cancer Risk Get access Jill Waalen Jill Waalen Correspondence to: Sue A. Bartow, M.D., Department of Laboratory Medicine and Pathology. University of Minnesota. Box 724-UMHC, 420 Delaware St. SE., Minneapolis, MN 55455 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 21, 3 November 1993, Pages 1712–1713, https://doi.org/10.1093/jnci/85.21.1712 Published: 03 November 1993