tbuckley/cabot-search huggingface dataset:
Abstract 62: The Coxsackie Virus B3 modulates Cardiac Ion Channels
Authors: Guiscard Seebohm, Katja Steinke, Ulrike Henrion, Nicole Ettischer, Frank Sachse, Matthias Rohbeck, Karin Klingel, Nathalie Strutz-Seebohm
Journal: Circulation Research (2014)

Infections with coxsackieviruses of type B (CVB) induce severe forms of acute and chronic myocarditis that are often accompanied by ventricular arrhythmias. The mechanisms underlying the development of virus-induced, life-threatening arrhythmia, remain largely elusive. Here, we show time-dependent CVB3-induced modulation of the cardiac ion channels Kv7.1, hERG1 and CaV1.2 in vitro. Channel protein localizations within cells and plasma membrane abundance are altered in infected mouse cardiac cells. In silico analyses of infected human myocytes suggest increased risk of arrhythmogenesis. These modifications are attenuated by the common Asian polymorphism KCNQ1-P448R, a genetic determinant preventing coxsackievirus-induced effects in vitro. This study provides a previously unknown explanation for the development of arrhythmias in enteroviral myocarditis, which will help to develop therapeutic strategies for arrhythmia treatment.
Prostate cancer treatment: A multidisciplinary approach
Authors: M. A. Fialk, S. E. Lerner, R. E. Stevens, H. J. Lee, K. Duffy
Journal: Journal of Clinical Oncology (2004)

4666 Backround: In the absence of randomized prospective trials the optimal therapy for localized prostate cancer (PC) remains to be proven. Decisions regarding definitive therapy {watchful waiting (WW), radical prostatectomy (RP), external beam radiotherapy (EXRT), brachytherapy (BT), EXRT+BT} becomes one of personal preference potentially influenced by the bias of the counseling physician. In an attempt to eliminate this bias we have implemented a novel multidisciplinary consultation program (MC) for patients with a new diagnosis of localized PC. Methods: 74 men (median age 62), with ≤cT2NXMX PC participated in the MC. Patients and families had the opportunity to meet simultaneously with a oncologic urologist, radiation oncologist, medical oncolgist and nurse to discuss their case and treatment options. Questionnaires were then mailed to the participants. Anonymity option provided. Results: 55/74 questionaire respondents. 31/55 MC very informative (provided new information and insights), 23/55 informative, and 0/55 redundant. 35/55 very useful, 18/55 useful, 1/55 not very useful, 1/55 confusing. 41/55 felt physicians were objective, 11/55 slightly biased, 1/55 biased. Compared to the initial consult (prior to the MC) the presentation of the treatment options were more objective (13/55), equally objective (37/55), more biased (1/55). Final decision making process: MC very useful (30/55), useful (22/55), not very useful (1/55), detrimental (0/55). 42/55 were either satisfied or very satisfied with final treatment selection. Conclusion: The best therapy for ≤cT2 PC remains to be proven. An objective presentation of the treatment options should be provided so that the patient and his family can make an infomed decision. 98% found the MC to be either useful or very useful in the final treatment selection process. The postitive feedback experienced with the MC will lead to the development of similar programs in our cancer program. No significant financial relationships to disclose.
Bedside, Benchtop, and Bioengineering: Physicochemical Imaging Techniques in Biomineralization
Authors: Neil M. Eisenstein, Sophie C. Cox, Richard L. Williams, Sarah A. Stapley, Liam M. Grover
Journal: Advanced Healthcare Materials (2016)

The need to quantify physicochemical properties of mineralization spans many fields. Clinicians, mineralization researchers, and bone tissue bioengineers need to be able to measure the distribution, quantity, and the mechanical and chemical properties of mineralization within a wide variety of substrates from injured muscle to electrospun polymer scaffolds and everything in between. The techniques available to measure these properties are highly diverse in terms of their complexity and utility. Therefore it is of the utmost importance that those who intend to use them have a clear understanding of the advantages and disadvantages of each technique and its appropriateness to their specific application. This review provides all of this information for each technique and uses heterotopic ossification and engineered bone substitutes as examples to illustrate how these techniques have been applied. In addition, we provide novel data using advanced techniques to analyze human samples of combat related heterotopic ossification.
Action of Bacterial Polysaccharide on Tumors. II. Damage of Sarcoma 37 by Serum of Mice Treated With &lt;italic&gt;Serratia Marcescens&lt;/italic&gt; Polysaccharide, and Induced Tolerance
Authors: W. Edward O'Malley, Betty Achinstein, Murray J. Shear
Journal: JNCI Journal of the National Cancer Institute (1962)

Administration of Serratia marcescens polysaccharide to normal mice was followed by the appearance of tumor-necrotizing activity in the circulating blood. Potency was assayed by intraperitoneal injection of the blood serum of treated mice into others bearing Sarcoma 37. This activity in the serum diminished rapidly; the higher the dose, the longer it persisted. Blood drawn shortly after injection of the polysaccharide possessed detectable potency following a dose as low as 20 µg. A second injection 4 days after the first one failed to produce analogous activity, even when the dose was more than doubled. This tolerance paralleled the previously reported refractoriness of tumors to repetition of treatment with the polysaccharide.
The impact of previous tracheostomy in patients with locally advanced squamous cell carcinoma of the larynx submitted to concurrent chemotherapy and radiation
Authors: F. L. Dias, D. Herchenhorn, I. A. Small, C. M. Araújo, C. G. Ferreira, J. Kligerman
Journal: Journal of Clinical Oncology (2007)

6004 Background: The combination of chemotherapy and radiotherapy is a standard treatment for locally advanced larynx cancer. Patients presenting with previous tracheostomy due to aiway obstruction have a worse clinical outcome when submitted to a total laryngectomy or radiotherapy; the impact of previous tracheostomy is not clear in patients submitted to chemotherapy combined with radiation. Methods: A single-institutional study, patients with stage III and IV laryngeal carcinoma were prospectively selected from 2000 to 2003. Treatment consisted of Cisplatin 100 mg/m 2 every three weeks for 3 cycles concurrent with radiotherapy to a total dose of 70.2 Gy. Prognostic factors like stage, age, performance status, chemotherapy completion, treatment response and previous tracheostomy were correlated on univariate and multivariate analysis with treatment response, progression-free and overall survival. Results: Forty-nine patients were selected, previous tracheostomy was performed in 12 (24,5%) before chemo/radiation therapy. Patients with tracheostomy had an inferior median overall cancer-specific survival (12 months versus 56 months), HR 2.37 (CI 95% 1.43–3.93) p=0.001, progression free-survival HR 2.8 (CI 95% 1.61–4.89) p&lt;0.001 and lower rates of complete responses (40 versus 75%). The impact of previous tracheostomy was not altered when adjusted by number of chemotherapy cycles, tumor stage, performance status, age or treatment response. On a cox regression analysis for overall cancer-specific survival it was the strongest prognostic factor HR 7.75 (CI 95% 2.75–21.84) p&lt;0.001. Conclusions: Previous tracheostomy is an independent negative prognostic factor for patients submitted to chemotherapy combined with radiation. Tracheostomty should be considered in the design of future studies and to select patients to different treatment strategies. No significant financial relationships to disclose.
Chemoprevention of &lt;italic&gt;N&lt;/italic&gt;-Nitroso-&lt;italic&gt;N&lt;/italic&gt;-methylurea-Induced Mammary Cancers by Pretreatment with 17&lt;italic&gt;β&lt;/italic&gt;-Estradiol and Progesterone&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: C J Grubbs, D R Farnell, D L Hill, K C McDonough
Journal: JNCI Journal of the National Cancer Institute (1985)

Because hormones of pregnancy are thought to alter the mammary gland such that the epithelial cells are less susceptible to future carcinogenic insults, the present study was conducted to determine the ability of short-term treatment with 17 beta-estradiol and/or progesterone, administered immediately after puberty, to prevent mammary cancers in rats subsequently exposed to N-nitroso-N-methylurea [(NMU) CAS:684-93-5]. Beginning at 40 days of age, female outbred Sprague-Dawley rats received 20 micrograms 17 beta-estradiol and/or 4 mg progesterone for 5 weeks. NMU (50 mg/kg body wt) was administered at 96 and 103 days of age (3 and 4 wk, respectively, after the last hormone injection). Pretreatment of rats with 17 beta-estradiol plus progesterone was highly effective in preventing mammary cancer induction (88% fewer cancers compared to the cancer incidence in rats pretreated with the hormone vehicle). Wholemounts of the mammary glands of rats treated with 17 beta-estradiol plus progesterone revealed that the gland was stimulated to a highly differentiated state (similar to that observed in late pregnancy). At the time of NMU treatment, the gland had involuted but was quite different from controls; i.e. an absence of terminal end buds and terminal ducts was noted. The short-term treatment with hormones did not induce tumors and did not interfere with subsequent reproductive and lactational performance. It is apparent that stimulation of the mammary gland to a highly differentiated state early in life can provide protection against future carcinogen exposure.
Long term air pollution exposure and COPD in SALIA: Discrepancies between ESCAPE results and published evidence in SALIA
Authors: Tamara Schikowski, Andrea Vierkötter, Dorothee Sugiri, Nicole Probst-Hensch, Nino Künzli, Ursula Krämer
Journal: European Respiratory Journal (2013)

Background: In a cross-sectional study in 1985 and 1994, women from the SALIA study showed a strong association of air pollution with COPD. In the ESCAPE project, 2008-2012, where data of lung function and exposure were used from a follow-up study in 2008, this association could not be replicated. Aim: To explore and identify the responsible changes explaining the discrepancies between ESCAPE results and published evidence. Method: Multiple regression analyses were use. Factors that differ between the two analyses were changed step by step to identify factors that are responsible for the discrepancies. Results: The baseline analysis showed a significant positive association between COPD and PM10 (OR: 1.68 (95%CI: 1.01-2.78)) per 10 µg/m3. The ESCAPE project analysis the showed a non-significant OR of 0.93 (95% CI: 0.72-1.21) for the outcomes. Differences in the ESCAPE analysis compared to the baseline analysis were the following: inclusion of a subgroup of surviving women (N=541 vs. N=2095), use of lung function data of 2008 with different spirometer, use of a more detailed exposure assessment in 2008 and use of a different set of covariates. The differences in result were due to the inclusion of surviving women as the prevalence of COPD at baseline was already lower in this subgroup in comparison to the whole group (2.1% compared to 3.5%) and the use of the lung function from 2008 as lung function deteriorates between baseline and 2008. Conclusion: The association of air pollution on COPD was less pronounced in the surviving women at follow-up than in all women from baseline. This might be due to the strong decline in PM10 pollution between 1984 and 2008.
New perspectives on the hepatitis B virus life cycle in the human liver
Authors: Peter A. Revill, Stephen A. Locarnini
Journal: Journal of Clinical Investigation (2016)

The central role of the transcriptional template of the hepatitis B virus (HBV), covalently closed circular DNA (cccDNA), has been difficult to study in patients with chronic hepatitis B (CHB) infection. In this issue of the JCI, Zhang and colleagues reveal a mosaic distribution of viral antigens and nucleic acids and a mismatch between HBV cccDNA, RNA, and expression of the hepatitis B surface antigen (HBsAg). These unusual patterns varied over the natural history of CHB, prompting the authors to propose a new three-stage model of the HBV life cycle at the single-cell level.
Spanish Women'S Perceptions of Mammography Screening
Authors: J.M. Baena-Cañada, P. Rosado-Varela, C. Cortés-Carmona, S. Estalella-Mendoza, P. Ramírez-Daffós, E. Arriola-Arellano, M.J. Gómez-Reina, J.A. Contreras-Ibáñez, A. Rueda-Ramos, J. Nieto-Vera, E. Benítez-Rodríguez
Journal: Annals of Oncology (2014)
Vinorelbine and capecitabine combination as first-line treatment in patients with metastatic breast cancer: Final results of a multicentric trial in Egypt
Authors: H. Elghazaly, H. Tawfik, M. Mahrous, M. M. Meshref, A. Sakr, N. Haddad
Journal: Journal of Clinical Oncology (2008)

1125 Background: The efficacy of vinorelbine with capecitabine was shown to be more than just additive in vitro. Moreover, vinorelbine-capecitabine combination demonstrated promising antitumor activity in the clinical setting. Based on this data we conducted a multicentric phase II study to evaluate the efficacy and safety of this combination. Methods: We report results for the 45 metastatic breast cancer patients enrolled (Nov 2005 to Nov 2006), first line treatment, at least one measurable lesion. Treatment schedule: vinorelbine 25 mg/m2 I.V. day 1 and 8, capecitabine 1,000 mg/m2 twice daily, day 1–14 q 21 days. Primary endpoint: objective response rate. Patients: Average age 49 years; range (28 -68). Median WHO PS 1; range (0–2). 96% of patients had received prior neo/adjuvant anthracycline based chemotherapy (CT) without taxanes. No adjuvant CT within the last 3 months. The most frequent metastatic sites were lung (76%), liver (49%), and bone (29%). 24% of pts had one metastatic site, 56% had 2, 18% had 3 and 2% had more than 3 sites. 6 pts (13%) had one or more metastatic sites associated to a local recurrence. Results: The median number of chemotherapy cycles was 6; range (3–6), total number of cycles: 244. All pts were evaluable for response. An objective tumor response was achieved in 29 pts 64%, (OR = CR + PR), complete response CR in 2 (4%) pts. 8 (18%) pts had stable disease. The median time to progression is 9 months. The median survival is not yet reached (median duration of follow-up of 13.5 months). The majority of adverse events were mild to moderate. No WHO grade 4 toxicities were noted. 6 (13%) pts developed Gr 3 neutropenia, Gr 3 nausea/vomiting and oral stomatitis were reported in 7 (16%) and 5 (11%) pts respectively. 3 patients developed Gr 3 hand foot syndrome. Conclusions: Vinorelbine-capecitabine combination shows high activity and good tolerance as first-line treatment for MBC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pierre Fabre Oncology
Measuring HER2-Receptor Expression In Metastatic Breast Cancer Using [<sup>68</sup>Ga]ABY-025 Affibody PET/CT
Authors: Jens Sörensen, Irina Velikyan, Dan Sandberg, Anders Wennborg, Joachim Feldwisch, Vladimir Tolmachev, Anna Orlova, Mattias Sandström, Mark Lubberink, Helena Olofsson, Jörgen Carlsson, Henrik Lindman
Journal: Theranostics (2015)

Purpose: Positron Emission Tomography (PET) imaging of HER2 expression could potentially be used to select patients for HER2-targed therapy, predict response based on uptake and be used for monitoring.In this phase I/II study the HER2-binding Affibody molecule ABY-025 was labeled with 68 Ga-gallium ([ 68 Ga]ABY-025) for PET to study effect of peptide mass, test-retest variability and correlation of quantified uptake in tumors to histopathology.Experimental design: Sixteen women with known metastatic breast cancer and on-going treatment were included and underwent FDG PET/CT to identify viable metastases.After iv injection of 212±46 MBq [ 68 Ga]ABY-025 whole-body PET was performed at 1, 2 and 4 h.In the first 10 patients (6 with HER2-positive and 4 with HER2-negative primary tumors), [ 68 Ga]ABY-025 PET/CT with two different doses of injected peptide was performed one week apart.In the last six patients (5 HER2-positive and 1 HER2-negative primary tumors), repeated [ 68 Ga]ABY-025 PET were performed one week apart as a test-retest of uptake in individual lesions.Biopsies from 16 metastases in 12 patients were collected for verification of HER2 expression by immunohistochemistry and in-situ hybridization.Results: Imaging 4h after injection with high peptide content discriminated HER2-positive metastases best (p<0.01).PET SUV correlated with biopsy HER2-scores (r=0.91,p<0.001).Uptake was five times higher in HER2-positive than in HER2-negative lesions with no overlap (p=0.005).The test-retest intra-class correlation was r=0.996.[ 68 Ga]ABY-025 PET correctly identified conversion and mixed expression of HER2 and targeted treatment was changed in 3 of the 16 patients.Conclusion: [ 68 Ga]ABY-025 PET accurately quantifies whole-body HER2-receptor status in metastatic breast cancer.
P0471 : NKp46 and trail are the major NK cell receptors involved in anti-HCV activity of NK cells in vitro
Authors: B. Krämer, C. Zwank, A. Glässner, P. Kokordelis, F. Wolter, D. Kaczmarek, P. Lutz, F. Göser, H.D. Nischalke, C.P. Strassburg, U. Spengler, J. Nattermann
Journal: Journal of Hepatology (2015)
Abstract 123: Survey Analysis of a Statewide CPR Initiative: Willingness in Comparison to Median Income and Training
Authors: Ashish R Panchal, Bethany D Panchal, Julie Stephens, Lisa Goldberg, Arthur B Sanders
Journal: Circulation (2014)

Background: Bystander CPR is provided in ~25% of out of hospital cardiac arrests in the US. To improve this low rate, the Save Hearts in Arizona Registry & Education program has initiated a multifaceted, statewide public chest compression only (CCO) CPR education campaign. It is unclear whether a statewide CCO-CPR campaign changes the intention of bystanders to perform CPR. It’s further unknown if this initiative affects willingness in populations with lowest survival and CPR performance.

Objective: Evaluate the willingness to perform CPR, in various income demographics, following a statewide CPR intervention.

Methods: Adult Arizona residents were surveyed at an academic medical center regarding performing CPR. They were asked their attitudes and feelings concerning performing CPR on strangers and family. Demographics were collected including age, gender, education, race and zip code which was used to incorporate census data for median income (separated as quartiles). Inclusion criteria were Arizona residents, age >18, and missing < 10% of survey data. CPR training was defined as CCO or formal CPR training.

Results: Total of 1302 surveys were collected with a final population of 1163. Mean age was 40 yo (95% CI: 38.8, 40.5) with 44% males (95% CI: 41, 47). Willingness to perform CCO-CPR on strangers or family was high at 84% and 92%, respectively. However, when evaluated against median income, individuals in the lower income quartiles were less likely to perform CPR compared to higher quartiles for both strangers (77%; 95% CI 73, 82; P = 0.003) and family (90%; 95% CI 87, 94; P = 0.025). In these lower quartiles, a third as many individuals received training in CPR compared to the higher quartiles (p <0.001). Logistic regression analysis is being completed to evaluate this association in relation to race, education and other confounders.

Conclusion: Public CPR interventions are effective in improving the willingness of bystanders to perform CPR. It is possible that CCO initiatives are not reaching the lowest quartile income populations which often have the lowest bystander CPR rates and highest mortality. Future CPR initiatives should be tailored to populations with highest mortality and who may not currently be receiving standard teaching initiatives.
Prediction of survival in early-stage non-small cell lung cancer based on kinase activity profiles.
Authors: R. Ruijtenbeek, V. Thijssen, R. van Suylen, L. Houkes, R. de Wijn, R. Hilhorst, A. C. Dingemans
Journal: Journal of Clinical Oncology (2010)

10642 Background: Prognosis of patients with non-small cell lung cancer (NSCLC) is poor, even in early-stage disease. At present, no reliable prognostic tests are available to identify early stage NSCLC patients with poor survival or to identify patients who might benefit from targeted adjuvant therapy. The aim of the current study was to evaluate the prognostic value of kinase activity profiles in early-stage NSCLC patients. Methods: A retrospective study was performed on two extreme groups of early stage NSCLC patients (stage IA-IIIA) who underwent a complete surgical resection. The groups consisted of short term survivors and long term survivors (survival duration from diagnosis < 24 months (n = 22) and > 48 months (n = 26) respectively). Tumor tissue cryosections were lysed in M-Per buffer supplemented with phosphatase and protease inhibitors. Kinase activity profiles were generated in the presence and absence of the protein tyrosine kinase inhibitor gefitinib on PamChip arrays comprising 144 tyrosine containing peptides derived from known human protein phosphorylation sites. Ratio's of inhibited vs. non-inhibited signals were used as input for multivariate analysis to classify samples. Results: Re-evaluation of hematoxilin/eosin stained cryosections confirmed that all tissue specimens contained at least 60% tumor tissue. A clear phosphorylation profile could be obtained from all samples. Profiles obtained in the absence of gefitinib, did not distinguish between patients with short survival and long survival, whereas ratios of inhibited vs. non inhibited signals resulted in a classifier able to predict survival. Interestingly, the inhibitory effects of gefitinib were stronger in patients with short survival as compared to patients with long survival. Positive predictive value and negative predictive value for the classifier were 80.7% (21/26) and 80.9% (17/21), respectively. Conclusions: This retrospective study of the ex vivo effect of kinase targeting agents on kinase activity profiles of individual patients with early stage NSCLC yielded a classifier able to predict prognosis in a set of 48 patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PamGene
ID3 Is a Novel Tumor Suppressor Gene in Burkitt Lymphom
Authors: Cassandra L Love, Dereje Jima, Zhen Sun, Rodney R. Miles, Cherie H. Dunphy, William W. L. Choi, Wing Y Au, Gopesh Srivastava, Patricia Lugar, David A. Rizzieri, Anand S. Lagoo, Leon Bernal-Mizrachi, Karen P. Mann, Christopher R. Flowers, Kikkeri Naresh, Andrew M. Evens, Amy Chadburn, Leo I. Gordon, Magdalena Czader, Javed Gill, Eric D. Hsi, Jenny Zhang, Vladimir Grubor, Shawn Levy, Anjishnu Bunerjee, David Dunson, Guojie Li, Andrea Moffitt, Adrienne Greenough, Matthew S. McKinney, Sandeep S. Dave
Journal: Blood (2012)