tbuckley/cabot-search huggingface dataset:
BRCA1 c.5181_5183delGTT (p.Val1688del) is a true pathogenic mutation that affects both protein stability and function: implications for genetic counseling.
Authors: A De Nicolo, S Pathania, E Parisini, KJ Branda, K Stoeckert, JE Garber
Journal: Cancer Research (2009)

Abstract Abstract #1106 Germ line mutations in the BRCA1 tumor suppressor gene are associated with a significantly increased lifetime risk of breast and/or ovarian cancers. Since genetic testing has become a routinely step in the clinical practice, the discrimination between pathogenic mutations and benign variants appears a mandatory task as it can facilitate risk estimation and surveillance, as well as implementation of cancer prevention and treatment strategies. Most of the deleterious BRCA1 mutations identified so far are frameshift or nonsense ones that result in a premature translational truncation of the protein; only a small percentage is represented by missense mutations residing in the N-terminal RING finger or in the C-terminal BRCT domains. Interestingly, a growing number of variants of unknown significance (VUSs) are being described, which lack ad hoc functional assays thus remaining unclassified with respect to their pathogenic or neutral effect.&amp;#x2028; Recently, disease-causality was predicted, based upon a multifactorial likelihood approach, for a BRCA1 VUS, c.5181_5183delGTT (p.Val1688del), recurrent in Italian breast/ovarian cancer families (Malacrida et al., 2008). The same VUS was also identified in one of the families recruited at the Dana-Farber Cancer Institute: pedigree analysis revealed early onset breast cancer in both the proband and her mother; family history confirmed Italian descent.&amp;#x2028; To gain insights into the specific risk associated with the BRCA1 c.5181_5183delGTT (p.Val1688del) VUS, we investigated its impact on BRCA1 function. The sequence variant causes a single amino acid in frame deletion that falls within the first of the two tandem BRCA1 BRCTs. A series of approaches, including protein stability assays and co-immunoprecipitation experiments, as well as structural modeling based on sequence alignment, were employed to characterize both the full-length mutant protein (ΔValBRCA1) and its C-terminal fragment.&amp;#x2028; We observed that ΔValBRCA1 displayed decreased stability when compared to the wild type counterpart. Moreover, when tested, interactions with known BRCA1 partners, BRIP1 and CtIP, were completely abrogated. In addition, ΔValBRCA1 failed to interact with Rap80 and was deficient in DNA damage response and repair by homologous recombination. These results demonstrate that BRCA1 c.5181_5183delGTT (p.Val1688del) is a true pathogenic sequence alteration and provide the first evidence of its effect on the stability and function of the encoded protein. We believe that our findings will impact the genetic counseling of those patients who harbor this newly defined mutation and their family members thus allowing them to benefit of appropriate risk assessment, prevention and therapeutic strategies. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1106.
The ‘2014 European guideline on the management of syphilis’ has now been published
Authors: M Unemo, M Janier
Journal: Eurosurveillance (2014)

Preview this article: The ‘2014 European guideline on the management of syphilis’ has now been published, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/19/45/art20957-en-1.gif
Long-term follow-up of short intensive multiagent chemotherapy without high-dose methotrexate (‘Orange’) in children with advanced non-lymphoblastic non-Hodgkin's lymphoma: a Children's Cancer Group Report
Authors: MS Cairo, MD Krailo, M Morse, RJ Hutchinson, RE Harris, CR Kjeldsberg, ME Kadin, E Radel, LJ Steinherz, E Morris, JL Finlay, AT Meadows
Journal: Leukemia (2002)
Abstract P2-06-02: Health Economic Impact of Risk Group Selection According to ASCO-Recommended Biomarkers uPA/PAI-1 in Node-Negative Primary Breast Cancer
Authors: VR Jacobs, R Kates, EJ Kantelhardt, M Vetter, M Schmitt, F Jaenicke, M Untch, C Thomssen, N. Harbeck
Journal: Cancer Research (2010)

Abstract Background Invasion factors uPA/PAI-1 are guideline-recommended (ASCO, AGO) biomarkers for decision support regarding adjuvant chemotherapy (CTX) in primary breast cancer (BC). Methods Potential savings in direct, per-patient expected costs of two leading CTX regimens (6xFEC or 3xFEC-3xDOC) resulting from uPA/PAI-1 test were calculated from a German health provider's perspective for a hypothetical 55 year old, N0, ER+, HER-patient in otherwise good health. Assumptions: patient always receives adjuvant endocrine therapy; without uPA/PAI-1 test, patient also receives CTX; with test, adjuvant CTX given only for high uPA/PAI-1 (60%); cost of testing all patients is included. Results Testing costs (with tissue handling) are 385€. Adjuvant CTX costs are saved in 40% of patients by testing; including medications, prophylaxis, diagnostics, additional supporting therapies and procedures, CTX costs about 20000€ for both regimens considered (6xFEC ∼18000€; 3xFEC+3xDOC ∼21000€); relapse medical costs were modeled at 40000€. Consider a low-uPA/PAI-1 patient: Survival curves without CTX were estimated using CHEMO N0 10y-disease-free survival (89%) plus endocrine therapy benefit (hazard ratio (HR)=0.7). Expected lost life years (LY) due to relapse (with versus without test) were estimated from corresponding survival curves using age-adjusted life expectancy (minus 2y post-relapse survival). Cost per life year gained in low-risk patients treated by adjuvant chemotherapy The figure shows estimated savings (∼18500€) per low-risk patient (lowest curve), survival impact (decreasing curve) and cost per LY of not giving the uPA/PAI-1 test (increasing curve), as the assumed adjuvant CTX benefit in the low-risk group (no testing) is varied between HR=0.8 and HR=0.99. If the health care provider were willing to pay 50000€ for 1 LY, then a HR of at most 0.85 would be required in the low-risk group. Very low CTX benefit (HR approaching 1) is associated with astronomical costs/LY. Conclusions In clinical practice, the fraction of G2 ER+ HER2- patients for whom CTX savings could be realized could be affected by 1. existence of sufficient tissue for the assay; 2. availability of logistics; 3. additional clinicopathological decision criteria. The main driver of cost utility in low-uPA/PAI-1 patients is their benefit (HR) for adjuvant CTX. Our estimates show that the uPA/PAI-1 test is likely to be cost effective even with respect to LY; its cost effectiveness is expected to be even stronger when quality of life or severe chemotherapy risks such as heart damage and leukemia are considered. Our model thus lends health economic support to current guideline recommendations that uPA/PAI-1 testing is beneficial in node-negative BC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-02.
Clinical Syndromes Associated with Deficient Lung Fibrinolytic Activity
Authors: Jack Lieberman
Journal: New England Journal of Medicine (1959)

THE fibrinolytic enzymes of the human organism constitute a complex system consisting of a circulating active enzyme (fibrinolysin or plasmin), its inactive precursor (profibrinolysin or plasminogen) and several blood and tissue activators and inhibitors.1 The widespread distribution of these substances within the tissues and body fluids2 suggests that they may have functions in addition to intravascular clot control. If this were true, a derangement of any component of this system could result in clinical manifestations related to these heretofore undescribed functions. The hemorrhagic syndrome of afibrinogenemia due to excessive intravascular fibrinolysin activity may be only one of several entities dependent . . .
1229 COMPARISON OF VIROLOGICAL RESPONSE BETWEEN RIBAVIRIN AND PEG-INTERFERON MONOTHERAPY DURING AUTOCHTONOUS CHRONIC HEPATITIS E VIRUS INFECTION
Authors: L. Alric, D. Bonnet, A. Palacin, S. Th'ebault, J.M. Peron, N. Sigur, F. Nicot, F. Abravanel, N. Kamar
Journal: Journal of Hepatology (2013)
Discordant Tc-99m Depreotide and F-18 FDG Imaging in a Patient with Poorly Differentiated Small-Cell Neuroendocrine Carcinoma
Authors: David T Nguyen, Toney Morakinyo
Journal: Clinical Nuclear Medicine (2002)

From the Departments of Nuclear Medicine* and Radiology,† Tripler Army Medical Center, Honolulu, Hawaii Received for publication July 17, 2001. Revision accepted November 8, 2001. The opinions expressed herein are those of the authors and are not necessarily representative of Tripler Army Medical Center, the United States Army, or the Department of Defense. Correspondence: David Nguyen, Department of Nuclear Medicine, Tripler Army Medical Center, Honolulu, Hawaii 96859. E-mail: [email protected]
META-ANALYSIS OF RANDOMIZED TRIALS COMPARING MULTIVESSEL VERSUS INFARCT ARTERY-ONLY REVASCULARIZATION FOR PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION AND MULTIVESSEL CORONARY ARTERY DISEASE
Authors: Rahman Shah, Sajjad A. Khan, Rohan Goswami, Jonathan Gardner, Mohamed Morsy, Yenal Harper
Journal: Journal of the American College of Cardiology (2016)
Nonspecific Iodine Accumulation in Surgical Suture Material Mimicking Follicular Thyroid Cancer Bone Metastasis in 131I Scintigraphy
Authors: Thomas Winkens, Sandor Nietzsche, Michael Gottschaldt, Martin Freesmeyer
Journal: Clinical Nuclear Medicine (2013)

A 23-year-old man with follicular thyroid carcinoma and cervical lymph node metastases showed a clear 131I focus on the skull after radioiodine therapy; therefore, an osseous metastasis was suspected. 131I and MRI fusion suggested the 131I focus to be adjacent to an epicranial suture from an early childhood trepanation for epidural hematoma. Radio-guided surgery found dark brown material to be the source of the radiation and successfully removed the material. Subsequent electron microscopy revealed a thread within the dark brown material, suggesting suture material as the cause of 131I accumulation.
THU0027 Cardiovascular Risk Profile in Systemic Lupus Erythematosus
Authors: D. Monova, S. Monov, R. Rashkov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease characterized by the presence of a plethora of autoantibodies and immune complex formation. Virtually every system and organ can be affected by SLE. Cardiovascular disease (CVD) is one of the most serious complications of systemic lupus erythematosus. <h3>Objectives</h3> The aim of this study is to investigate the prevalence of cardiovascular diseases in patients with systemic lupus erythematosus and estimate the associated risk factors for CVD. <h3>Methods</h3> Patients with CVD were identified on the basis of medical record documentation. Stepwise multivariate logistic regression was used to assess the risk factors of CVD. Of the 256 patients with SLE, 57 had CVD. The demographic data and the clinical data including SLE duration, therapeutic regimen, renal pathological data, estimated glomerular filtration rate (eGFR), SLE Disease Activity Index (SLEDAI), and associated biochemical parameters were analyzed. Cardiovascular ultrasound was used for detecting and analyzing the cardiovascular structural and functional abnormalities. <h3>Results</h3> Fifty-seven cases of CVD were found in the 256 SLE cases (22,27%). After age stratification, CVD showing a tendency to increase with age (P&lt;0,005). The prevalence of CVD differed significantly between patients with and those without lupus nephritis (P&lt;0,005). Among the 57 patients with CVD, 35,09% (22/57) had left ventricular hypertrophy, 31,58% (19/57) had congestive heart failure, 15,79% (9/57) had stroke, 7,01% (4/57) had angina pectoris, and 5,26% (3/57) had peripheral CVD. Compared to those without CVD, patients with CVD had a longer SLE duration (P&lt;0,005), a longer time of steroids treatment (P&lt;0,05), a higher blood pressure (P&lt;0,0001), a lower eGFR (P&lt;0,001), and a lower concentration of HDL (P&lt;0,005). Logistic regression analysis showed that SBP, eGFR, HDL, SLE duration, SLEDAI index, serum C3 and hs-CRP were the risk factors for CVD in SLE patients (P&lt;0,05). <h3>Conclusions</h3> SLE is associated with a high risk of CVD which increases with age, and SLE patients with lupus nephritis have an even higher risk for CVD. SBP, eGFR, HDL, SLE duration, SLEDAI index, serum C3 and hs-CRP are the risk factors for CVD in SLE patients. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5603
Abstract 1505: The role of cathepsin B in colorectal tumorigenesis
Authors: Benjamin Bian, Sébastien Mongrain, Francois Boudreau, Nathalie Rivard
Journal: Cancer Research (2011)

Abstract Many cancers express elevated protease levels which contribute to certain aspects of tumor behavior such as growth and metastatic spread. Specifically, elevation of the cysteine protease cathepsin B has been shown to correlate with malignant progression of tumors. The majority of reports on cathepsin B expression in tumors have focused on measurements of activity or protein staining. However, multiple transcripts species have been detected resulting from alternative splicing in the 5’- or 3-untranslated regions, and possibly the use of alternative promoter regions. The specific role of these variants remains to be established. Methods: Expression of cathepsin B was analyzed in normal human intestinal epithelial cells (HIEC) and colorectal cancer cell lines (Caco-2/15, HCT116, DLD1, HT29, SW480, T84, Colo205) by qPCR and Western blot. The role of cathepsin B was examined in HT29 and DLD1 cell lines through recombinant lentiviruses encoding anti-cathepsin B short hairpin RNA (shRNA). Results: RT-PCR analyses demonstrated that the levels of the full transcript for cathepsin B containing exons 1-12 (CB) were similar between normal and cancerous cell lines. By contrast, the splice variant lacking exons 2 and 3 (CB-2,3) was expressed only in cancer cells and in biopsies from human colorectal tumors when compared to the adjacent healthy tissues. Immunofluorescence studies showed that this novel tumor form of cathepsin B (CB-2,3) was associated with nuclei and mitrochondria while the full-length cathepsin B protein (CB) was found in the lysosomes. Western blot analyses on culture media showed a strong secretion of various cathepsin B isoforms by cancer cell lines. The lentiviral infection of a shRNA which specifically knocked-down cathepsin B expression, while decreasing enzyme activity in cell lysates, did not influence colorectal cancer cell proliferation under anchorage-dependent conditions. By contrast, decrease of cathepsin B expression in HT29 and DLD1 colon cancer cell lines resulted in a marked reduction of their capacity to grow in soft agar. Levels of β-catenin protein and phosphorylated ERK1/2 were not affected following cathepsin B silencing in contrast to phosphorylated Akt which was significantly reduced. Further, migration and invasion through Matrigel was reduced by 60% in cells expressing the shRNA against cathepsin B compared to cells expressing a control shRNA. Conclusion: These results suggest that the alternative splicing of cathepsin B could contribute to the aberrant intracellular trafficking and function of cathepsin B in colorectal cancer. 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 1505. doi:10.1158/1538-7445.AM2011-1505
FRI0432 Comparison of Pregnancy Outcomes in Women with Juvenile and Adult Onset Systemic Lupus Erythematosus:
Authors: M.A. Saavedra, P. Cruz-Dominguez, S. Morales, A. Sanchez, L.J. Jara
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Juvenile-onset systemic lupus erythematosus (JSLE) is characterized by severe organ involvement. Information about pregnancy in these patients is very limited. <h3>Objectives</h3> Compare the maternal and fetal outcomes in women with juvenile-onset systemic lupus erythematosus (JSLE) with adult-onset SLE (ASLE). <h3>Methods</h3> We retrospectively studied a cohort of pregnant women with SLE (ACR 1997) between January 2005 and August 2013. Patients were assessed in each trimester and postpartum. Two groups were compared, pregnancies in women with JSLE (onset &lt;18 years) and ASLE (onset ≥18 years). Clinical, biochemical and immunological characteristics of women, along with maternal and fetal complications, were recorded. Statistical analysis included descriptive statistics, chi square, Student t test and logistic regression; odds ratios (OR) with confidence intervals (CI) of 95% were calculated. For the analysis each pregnancy was considered as an independent event. <h3>Results</h3> We included 186 pregnancies (58 with JSLE and 128 with ASLE) in 180 patients. Women with JSLE were younger at the time of pregnancy (23.5±4.6 vs 28.6±4.8 years, p&lt;0.0001), had a longer history of lupus (9.6±5.4 vs 3.9±3.1 years, p&lt;0.0001) and had a higher frequency of primiparity (63% vs 41.4%, p=0.005), hematologic manifestations (41.4% vs 2.4%, p=0.01), lupus nephritis (55.2% vs 26.6%, p≤0.0001) and positive anticardiolipin antibodies (40% vs 29%, p=0.04). There were no differences in maternal (53.4% vs 47.7%, p=0.46) or fetal complications (48.3% vs 61.7%, p=0.08) in both groups (Table). In the logistic regression analysis, the risk factors for the development of maternal complications were: disease activity before pregnancy (OR 5.4, 95%CI 1.6-18.0, p=0.005) and primiparity (OR 2.5, 95%CI 1.2-5.0, p=0.009); and for fetal complications it was preeclampsia (OR 9.3, 95%CI 1.9-43.7, p=0.05). <h3>Conclusions</h3> Although with more severe organic involvement, women with JSLE have maternal and fetal outcomes similar to ASLE. <h3>References</h3> Silva CAA, et al. J Rheumatol 2008;35:1414-8. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3060
AB0130 Ultrasound monitoring of the synovial thickness after 166-holmium-phytate radiosynoviorthesis seven years results phase III prospectiv study
Authors: M. Szentesi, Z. Farbaky, P. Geher
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To measure the synovial thickness after 166-Holmium radiosynoviorthesis by sonography. <h3>Methods</h3> Phases III, prospectiv study. 33 patients suffering from chronic synovitis, rheumatoid arthritis were examined. The protocol commenced with screening. The patients were selected according to inclusion and exclusion criteria. <i>Patients:</i> Gender (male/female): 7-23; Age: 57,13 (37-77) Stage of knee joint x-ray (I/II): 7/23; Duration of synovitis (years): 7,38 (0,5-27), Duration of disease (years): 9,1 (1-27); Number of punctures before the Ho-166 treatment: 12,8; Number of steroid injections before the treatment: 12.9 <i>Holmium phytate injectable suspension marked by 600 MBq <sup>166</sup>Holmium phytate injectable suspension</i>, and 40 mg of 1 ml triamcinolone acetonide and 1 ml of lidocaine 1%. There were 84 months follow-up period after the administration of the isotope. Inflammatory activity of the affected knee-joint was tested prior to treatment, and the 3th and 3, 6 12, 24, 36, 48, 60, 72 and 84 months after treatment. We measured the synovial thickness the following locations: In the midline, lateral and medial, by the condylus of femur medial and lateral. <h3>Results</h3> During the study period, inflammation decreased. In the first seven years excellent and good results were recorded in 93.3%. Seven years after radiosynoviorthesis 93.3% of patients did not need another punction. The thickness of the synovia decreased significantly. We find a significant correlation between the synovial thickness and the clinical improvenes. <h3>Conclusions</h3> The 166-Holmium-phytate is an effective new radiopharmacon in the treatment of synovitis. We detect the clinical improvement by sonography. The effective dose is 555-925 MBq. <h3>References</h3> Szentesi M., Környei J., Antalffy M., Törkö J., Tόth Gy., Jánoki Gy., Balogh L. Study of intraarticular application of 166-Holmium IHPP in rabbits. World Journal of Nucl. Med. 1. Suppl. 2. S243. Sept. 2002. <h3>Disclosure of Interest</h3> None Declared
PREDICTIVE ACCURACY OF MICROWAVE RADIOMETRY IN SYMPTOMATIC CAROTID PLAQUE IDENTIFICATION IN ISCHEMIC STROKE
Authors: Georgios Benetos, Konstantinos Toutouzas, Maria Drakopoulou, Christina Deligianni, Konstantinos Spengos, Andreas Synetos, Eleftherios Tsiamis, Elias Siores, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2015)
Abstract 279: Increased Met receptor activation mediates enhanced cell invasion upon mutant p53 expression in esophageal squamous cell carcinoma
Authors: Katharine D. Grugan, Charles G. Miller, Carmen Z. Michaylira, Andres J. Klein-Szanto, Hiro Nakagawa, Anil K. Rustgi
Journal: Cancer Research (2010)

Abstract Esophageal squamous cell carcinoma (ESCC), a type of squamous cell cancer, is one of the most aggressive forms of human cancer with poor prognosis due to late diagnosis and metastasis. Common genomic alterations in ESCC include p53 mutations and overexpression of oncogenes such as cyclin D1, EGFR, and Met. Using an invasive primary esophageal epithelial cell model system genetically transformed by the overexpression of EGFR and p53R175H, we find novel evidence of cross-talk between p53R175H and the Met receptor tyrosine kinase. Increased Met receptor activation is observed upon expression of p53R175H and is further enhanced upon subsequent overexpression of EGFR. Increased Met activation is observed also in a number of human ESCC cells lines that harbor either p53 genetic mutations or are p53 null. Met phosphorylation can be inhibited using two small molecule compounds (CP31398 and 5-iminodaunorubicin) that have been demonstrated previously to activate wild-type p53 signaling through distinct mechanisms, thereby providing further evidence to a link between these two pathways. Both CP31398 and 5-iminodaunorubicin blocked invasion of the genetically transformed primary esophageal epithelial cells (EPC-hTERT-EGFR-p53R175H) suggesting that the mechanism of increased invasiveness upon EGFR and p53R175H expression may be mediated by Met activation. In aggregate, mutant p53 and Met appear to cooperate to foster tumor invasion and this novel linkage has not been reported previously. These results provide further implications to the use of combinatorial therapeutics directed at Met and mutant p53 in ESCC and other squamous cell cancers. 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 279.