tbuckley/cabot-search huggingface dataset:
Abstract 828: Design, synthesis and biological evaluation of peptide inhibitors of the Keap1-Nrf2 protein-protein interaction
Authors: Rowena Hancock, Helene Bertrand, Shama Naz, Tadayuki Tsujita, John Hayes, Geoff Wells
Journal: Cancer Research (2011)

Abstract Background: Compounds that block the cellular effects of carcinogens have the potential to be cancer chemopreventive agents. A number of dietary constituents such as sulforaphane found in broccoli and curcumin found in turmeric increase the expression of antioxidant response element (ARE) genes involved in detoxifying reactive primary metabolites. The mode of action of these chemopreventive agents has been determined as an interaction with cysteine residues in the protein Keap1, this interaction causes Keap1 to release its binding partner, the transcription factor Nrf2. The free Nrf2 then translocates to the nucleus and up-regulates ARE dependent genes resulting in cellular protection against reactive species (McMahon et al., 2003). Aims: Our aim is to develop compounds that directly inhibit the Keap1-Nrf2 protein-protein interaction and thereby enhance Nrf2 activity by a mechanism different to that of existing chemopreventive agents. Such compounds will have the potential to be useful molecular probes for studying the Keap1-Nrf2 interaction and the Nrf2 signaling pathway in detail and also as candidate preventive agents for cancer. Methods: A series of linear peptides based on the high affinity binding motif of Nrf2 (the ETGE sequence) were designed, synthesized and screened to determine the optimum chain length for β-turn formation and interaction with the Keap1 protein. A second generation of peptides with changes to the sequence were synthesized to improve the binding profile. The peptides were synthesized using standard Fmoc chemistry and were purified by preparative HPLC, then lyophilized prior to use. The peptides were characterized by 1H-NMR, HPLC, LC-MS and high resolution MS. Results: The peptides were synthesized successfully and were shown to cause inhibition of the Keap1-Nrf2 protein-protein interaction, determined using a fluorescence polarization assay developed in our laboratory. A number of the sequence change peptides have equivalent or superior activity to the native Nrf2 sequence. Conclusion: In vitro tests have shown that the peptide sequence, structure and length are important for inhibition of the protein-protein interaction and the data have allowed us to propose an initial structure activity relationship for the Keap1-peptide interaction. The results and their implications for future drug design will be presented. Reference: McMahon, M., Itoh, K., Yamamoto, M., Hayes, J. (2003) J. Biol. Chem. 278, 21592-21600 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 828. doi:10.1158/1538-7445.AM2011-828
Primary pure signet-ring cell carcinoma of the anus: a case report with immunohistochemical study
Authors: T. Terada
Journal: Endoscopy (2014)

Although several cases of signet-ring cell carcinoma (SRCC) in the colorectum have been reported [1] [2], there have been no reports of SRCC in the anus. The case presented here is the first reported case of primary pure SRCC of the anus.
THREE-DIMENSIONAL ECHOCARDIOGRAPHIC APPROACH FOR AUTOMATED QUANTIFICATION OF LEFT ATRIAL VOLUME USING AN ADAPTIVE ANALYTICS ALGORITHM: INITIAL VALIDATION STUDY
Authors: Diego Medvedofsky, Wendy Tsang, Masaaki Takeuchi, Lynn Weinert, Megan Yamat, Amit Patel, Ivan Salgo, David Prater, Victor Mor-Avi, Roberto Lang
Journal: Journal of the American College of Cardiology (2016)
TRANSCATHETER AORTIC VALVE IMPLANTATION WITH OR WITHOUT PRE-IMPLANTATION BALLOON AORTIC VALVULOPLASTY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Rodrigo Bagur, Chun Shing Kwok, Luis Nombela-Franco, Peter Ludman, Mark de Belder, Sandro Sponga, Mark Gunning, James Nolan, Bob Kiaii, Pantelis Diamantouros, Michael Chu, Patrick Teefy, Mamas A. Mamas
Journal: Journal of the American College of Cardiology (2016)
PTU-145 Incidence of Eosinophilic Oesophagitis in a New Zealand Population: A Retrospective Analysis: Abstract PTU-145 Table 1
Authors: I A Murray, A Lee, C Tan, M Lau, J Palmer, M Schultz
Journal: Gut (2013)

<h3>Introduction</h3> Eosinophilic oesophagitis (EO) is the diagnosis in 10–15% of dysphagic patients in European and N American studies, most frequent in men aged less than 50 years. It is precipitated by aero-allergens. Diagnosis requires &gt; 20 eosinophils per hpf on oesophageal biopsies. We investigated its incidence in a New Zealand population where the genetic profile is similar (92% NZ European descent) but the environmental exposure to flora very different. <h3>Methods</h3> A retrospective review of 871 patients investigated by gastroscopy for dysphagia from 2006–11 at Dunedin hospital. Age, sex, endoscopic findings and whether biopsied were recorded from the endoscopy database. Histology was determined from the hospital PAS system and equivocal cases reviewed by a consultant histopathologist. Sex and age differences were interrogated with chi-squared and <i>P</i> &lt; 0.05 was considered significant. <h3>Results</h3> Average age of all patients was 68.7 years, 57.1% male. Common diagnoses were normal (27.7%), oesophagitis (21.7%), cancer (11.2%), dysmotility (7.3%), peptic stricture (5.0%). 20 patients (12 male, mean age 45.5 years) had EO. 5 of these had endoscopic abnormalities (2 × ridges, 2 × Schatzki rings, 1 × furrows). 351 patients (40.9%) had oesophageal biopsies, but only 86 of 434 where the underlying cause was not evidence ie no cancer, oesophagitis or peptic stricture. EO incidence was 2.3% of all patients, 5.7% of those biopsied but 23.2% of those where an alternative diagnosis was not evident. Annual incidence varied from 1.1 to 4%. The frequency of biopsies was greater in 2011 (73.6%) than previous years (26.9–44.1%) but the number of cases identified did not differ significantly (3.4–9.0% of those biopsied). <h3>Conclusion</h3> EO appears less frequent in a New Zealand dysphagic population than in previous Northern hemisphere studies although this might be due to few biopsies where no macroscopic abnormality was seen. Biopsies are more frequent in men than women but EO no more likely. Biopsies are not more frequent in younger patients ( &lt; 50 y.o) but EO is much more frequent. The exact incidence of EO and reasons for discrepancies with previous studies merit further investigation. <h3>Disclosure of Interest</h3> None Declared
Expression of Blood-Group Antigen A — A Favorable Prognostic Factor in Non-Small-Cell Lung Cancer
Authors: Jin S. Lee, Jae Y. Ro, Aysegul A. Sahin, Waun K. Hong, Barry W. Brown, Clifton F. Mountain, Walter N. Hittelman
Journal: New England Journal of Medicine (1991)

New prognostic factors are needed to guide the treatment of patients with non-small-cell lung cancer. We evaluated the prognostic value of altered expression of ABH blood-group antigens, which has been implicated in the multistep process of carcinogenesis and tumor progression.
The Public's Views about Medicare and the Budget Deficit
Authors: Robert J. Blendon, John M. Benson
Journal: New England Journal of Medicine (2011)

Despite many years of dire warnings about the serious problems for the federal deficit posed by the projected growth in Medicare spending, it has been difficult for political leaders in Washington to find a long-term solution to this problem. One factor contributing to the continuing impasse has been the role played by public and voter opinion. We examined this issue through an analysis and review of 21 opinion polls for a project supported by the Robert Wood Johnson Foundation (see Opinion Poll box).The polling results suggest four reasons for this impasse. First, Medicare remains very popular with the public and . . .
Female Circumcision as a Public Health Issue
Authors: N Toubia
Journal: New England Journal of Medicine (1994)

Female circumcision is practiced in 26 African countries, and it is estimated that at least 100 million women are circumcised. The mildest form is clitoridectomy and the more severe type is infibulation. Girls are commonly circumcised between the ages of 4 and 10 years. Since the operator is usually a nonprofessional without surgical experience, complications are common: hemorrhage and severe pain that can even result in shock and death. The most common long-term complication is the formation of dermoid cysts in the line of the scar. Childbirth adds other risks for infibulated women and vesicovaginal fistula is often the result. The attendant urinary incontinence leads to ostracism of these women. In sum, female circumcision is a major contributor to childhood and maternal mortality and morbidity in communities with poor health services. The physical complications add to the psychological trauma: many infibulated women have a syndrome of chronic anxiety and depression arising from their condition, intractable dysmenorrhea, and the fear of infertility. The psychological sequelae of immigrant women who live in societies where such practice is condemned is even worse and may need professional counseling to address their sexual identity and cultural identification. Tightly infibulated women require clinical intervention for deinfibulation in order to preclude serious maternal and fetal complications during childbirth. Reinfibulation is medically harmful and even though some women request it, health professionals who comply are ethically reprehensible. In Sweden a 1982 law makes all forms of female circumcision illegal, as does a law that was passed in the United Kingdom in 1985. In France several cases were brought against parents under child abuse laws for circumcising or attempting to circumcise their French-born daughters. In the United States a 1993 bill drafted by the Congressional Women's Caucus would make the practice illegal and fund a program to assist immigrant communities to deal with the problem.
Abstract P1-15-04: The relationship of relative dose intensity and supportive care to febrile neutropenia rates in patients with early stage breast cancer receiving chemotherapy: a prospective cohort study of chemotherapy-associated toxicity
Authors: E Culakova, MS Poniewierski, AF Wogu, NM Kuderer, J Crawford, DC Dale, GH Lyman
Journal: Cancer Research (2012)

Abstract Background: Febrile neutropenia (FN) represents a major dose-limiting toxicity of cancer chemotherapy resulting in considerable morbidity, mortality, and cost. Patients have the highest risk of the initial neutropenic event in cycle 1 when most patients receive full dose chemotherapy. This study evaluates time course of neutropenic events in patients receiving chemotherapy for early-stage breast cancer (ESBC) and supportive care interventions that modify FN risk in ESBC patients treated in actual oncology practice. Methods: A prospective cohort study of adult cancer patients with solid tumors or lymphoma starting a chemotherapy regimen was conducted at 115 U.S. sites. Toxicities associated with chemotherapy were recorded in up to 4 cycles including severe neutropenia (SN), FN, and infection. Documented clinical interventions included reductions in chemotherapy relative dose intensity (RDI), the use of colony-stimulating factors (CSFs), and antibiotics. Results: A total of 1202 ESBC patients starting chemotherapy were analyzed, of which 1154, 1099, and 896 reached the midcycle of cycles 2, 3, and 4, respectively. While the majority of neutropenic and infection events occurred in cycle 1, decreasing rates of FN and infection in later cycles correlated with increasing reductions in dose intensity and increased use of CSFs and antibiotics. The overall risk of FN in all patients combined was 16.3 %. It reached 21.1% for patients who started with planned RDI≥85% and without primary CSF prophylaxis. There was no significant difference in FN rates by menopausal status or hormone receptors. Conclusions: While the risk of neutropenic complications is highest during the first cycle of chemotherapy, reductions in neutropenic events during subsequent cycles are associated with reduced chemotherapy dose intensity or increased use of supportive care measures. Nevertheless, the cumulative risk of neutropenic events remains high in ESBC patients receiving full dose chemotherapy without prophylactic measures overall and across menopausal and hormone receptor subgroups. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-15-04.
Needle Aspiration of Primary Spontaneous Pneumothorax
Authors: Mathieu Pasquier, Olivier Hugli, Pierre-Nicolas Carron
Journal: New England Journal of Medicine (2013)

A large, primary spontaneous pneumothorax or a pneumothorax that causes clinically significant breathlessness requires active intervention. This video reviews the techniques and equipment required to perform needle aspiration of a primary spontaneous pneumothorax in adults.
P965 PERSONALIZED THERAPY WITH SORAFENIB FOR HEPATOCELLULAR CARCINOMA
Authors: G. Cabibbo, M. Iavarone, M. Maida, A. Di Martino, E. Orlando, C. Zavaglia, A. Grieco, E. Villa, F. Piscaglia, V. Di Marco, M. Colombo, A. Craxì, C. Cammà
Journal: Journal of Hepatology (2014)
P294 THE LIVER CONDITIONAL KNOCKOUT OF Cyp51 FROM CHOLESTEROL SYNTHESIS SHOWS FEATURES OF NON-ALCOHOLIC FATTY LIVER DISEASE
Authors: G. Lorbek, M. Pesrse, J. Jeruc, P. Juvan, R. Keber, M. Lewinska, I. Bjorkhem, S. Horvat, D. Rozman
Journal: Journal of Hepatology (2014)
A8.15 Enzymatic lipid oxidation by 12/15-lipoxygenase regulates maturation and function of dendritic cells
Authors: Tobias Rothe, Olga Oskolkova, Alexander Steinkasserer, Valery N Bochkov, Georg Schett, Elisabeth Zinser, Gerhard Krönke
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Upon the encounter of pathogens, dendritic cells (DCs) undergo a process of maturation, which allows them to initiate and orchestrate T-cell-driven immune responses. To avoid random T-cell activation and autoimmunity, respectively, DC maturation has to be tightly controlled. Here we aimed to elucidate the role of 12/15-lipoxygenase (12/15-LO)-mediated enzymatic lipid oxidation during DC-activation/maturation and the fine-tuning of the consecutive T-cell response. <h3>Materials and Methods</h3> To delineate the role of 12/15-LO in DCs, we analysed the phenotype of 12/15<sup>-/-</sup> bone marrow-derived DCs and performed the model of experimental autoimmune enzephalomyelitis (EAE) in wild type and 12/15-LO<sup>-/-</sup> mice. <h3>Results</h3> Differentiated bone marrow-derived DCs expressed 12/15-LO and were enriched in 12/15-LO-specific lipid oxidation products. Deletion of this enzyme resulted in enhanced DC maturation and a shift in their cytokine expression profile, which favoured the differentiation of Th17 T-cells. In contrast, both the activation of DCs and the development of Th17 T-cells were attenuated by exposure to 12/15-LO-derived oxidised phospholipids. The analysis of the lymphatic tissues of 12/15-LO-deficient mice confirmed an enhanced maturation of CD11c<sup>+</sup>CD11b<sup>+</sup>CD8<sup>-</sup> DCs as well as an increased differentiation of Th17 cells that was paralleled by an exacerbation of Th17-driven autoimmune disease. <h3>Conclusions</h3> Our data identify 12/15-LO as novel factor modulating the function of DCs and indicate a central, and so far unrecognised, role for enzymatic lipid oxidation during the shaping of the adaptive immune response.
AB1039 Motives for Physicians' Participation in Clinical Registries
Authors: F. Siracusa, A. Scherer, A. Finckh
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The pharmaceutical industry, regulators and the rheumatology community have recognised the need for observational studies to monitor safety and real world long-term effectiveness of biotherapies. Physician readiness and motivation to contribute information and data to registries, however, has received little attention. <h3>Objectives</h3> To examine factors associated with physicians9 participation in a clinical registry. <h3>Methods</h3> The Swiss Clinical Quality Management (SCQM) for rheumatic diseases is a population-based cohort of patients, affected by various rheumatic diseases, that is sponsored by the Swiss Society of Rheumatology. More than 80% of Swiss rheumatologists have registered patient information in the SCQM database without financial compensation of any sort. In order to understand the physicians9 motivations to participate, the SCQM queried all Swiss rheumatologists with a series of specific questions. A descriptive analysis was performed on the results of the questionnaire. <h3>Results</h3> In February of 2010, 480 rheumatologists received the SCQM participation survey. Of these, 164 (33%) answers were received. Twelve percent of participants declared no participation in the registry, while the remaining 88% declared the input of at least one patient in the registry. The most common reasons motivating participation were feedback on patients9 disease characteristics or quality management (69%), interest in Swiss rheumatology research (80%) and finally, health insurance aspects (∼36%). In the results of the SCQM survey, interest in research was the same in all types of institutions (hospital, university hospital, private practice), seen at 80%. Furthermore, there was a similar distribution throughout all categories regarding the positive benefits of receiving feedback from the SCQM database, other participating physicians and researchers. Among non-participants, fifty-nine percent stated that lack of time for additional administrative tasks was the reason for not registering patient data in the SCQM database. <h3>Conclusions</h3> While the importance of clinical registries has greatly increased over the past decades, it is critical to maximise the participation of physicians by addressing their various needs and concerns. The driving forces for participation, as well as the de-motivating factors, may vary by work setting, age groups and other factors. These factors need to be addressed specifically to keep participating physicians involved and to engage rheumatologists who do not currently use clinical registries. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5702
Increased Synthesis of Prostaglandin-E-like Material by Platelets from Patients with Diabetes Mellitus
Authors: Perry V. Halushka, Dan Lurie, John A. Colwell
Journal: New England Journal of Medicine (1977)

We studied the effects of ADP, epinephrine, collagen and arachidonic acid on platelet production of immunoreactive prostaglandin-E-like material and aggregation in 17 subjects with diabetes mellitus and 21 matched controls. Plateletrich plasma obtained from patients synthesized significantly (P less than 0.05) greater quantities of the prostaglandin-E-like material after exposure to 1 muM ADP, 1, 2 and 5 muM epinephrine and 1 microgram per milliliter of collagen than platelet-rich plasma obtained from controls. That obtained from the diabetic patients was significantly more sensitive (P less than 0.001) to the aggregating effects of the prostaglandin precursor, arachidonic acid, in vitro as compared to controls. Diabetic platelet-rich plasma metabolized arachidonic acid (0.5 mM) to immunoreactive prostaglandin-E-like material at a significantly greater rate (P less than 0.05) and extent (P less than 0.001) than that of controls. Thus, platelets obtained from diabetic patients possess increased activity of the prostaglandin synthetase system, and this characteristic may be related to the increased platelet aggregation associated with the disease.
What is a Freestanding Cancer Center?
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article What is a Freestanding Cancer Center? Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 3, 1 February 1989, Pages 183–185, https://doi.org/10.1093/jnci/81.3.183 Published: 01 February 1989
Abstract P6-05-02: Endocrine biomarkers in response to AR-inhibition with bicalutamide for the treatment of AR(+), ER/PR(−) metastatic breast cancer (MBC) (TBCRC011)
Authors: A Gucalp, S Tolaney, SJ Isakoff, J Ingle, MC Liu, L Carey, KL Blackwell, H Rugo, L Nabell, A Forero, V Stearns, L Momen, J Gonzalez, A Akhtar, DD Giri, S Patil, KN Feigin, CA Hudis, TA Traina
Journal: Cancer Research (2012)

Abstract Background: Our group and others have identified a subset of ER/PR(−) breast cancers characterized by expression of the androgen receptor (AR) and androgen-dependent growth (Doane 2006). We conducted a proof-of-concept multicenter phase II study to test the efficacy of the AR-antagonist, bicalutamide for the treatment of AR(+) ER/PR(−) MBC (NCT00468715). Results of the primary endpoint, clinical benefit rate (CBR), were presented at ASCO (Gucalp 2012). Data for the impact of bicalutamide on circulating hormone levels in women are limited. Elevations in serum testosterone (T) and estradiol (E) have been observed for men treated with bicalutamide. We hypothesized comparable patterns of change in circulating endocrine markers in response to bicalutamide for women with MBC. Methods: Patients (pts) with AR(+) (IHC ≥10%), ER/PR(−) (IHC &amp;lt;10%) MBC were eligible for treatment (tx) if ECOG performance status ≤2 and normal organ function regardless of menopausal status. There was no limit to prior tx except prior trastuzumab required if HER2(+). Tx consisted of bicalutamide 150mg orally daily in 28-day cycles (C). Toxicity assessed q4 weeks, response q12wks. Primary endpoint was CBR. Peripheral blood was collected for total and free T, E and sex hormone binding globulin (SHBG) at baseline, start of C2 (C2) and at end of study (EOS). Standard institutional assays were used. A Wilcoxon signed-rank test was done to compare baseline to C2 and EOS values. Results: 26 patients with AR(+) ER/PR(−) MBC were treated on study. Evaluable number (n) of pts at baseline, C2 and EOS are 26, 26 and 19 respectively. Two pts remain on study. Menopausal status: pre=2, post=24. Baseline median total and free T and estradiol were consistent with expected norms, however a wide range was observed (Table). There were no significant differences observed for median free T, total T, E or SHBG between baseline and C2 or baseline and EOS. Changes in hormone levels could not be stratified by menopausal status or response to bicalutamide given small sample size. Given the wide range of baseline values, we examined the percent change for each endocrine biomarker from baseline to C2 and EOS. As shown in the Table, there was no difference in median percent change observed across time points for each biomarker. Conclusions: No discernible patterns of change in T, E or SHBG were observed in response to bicalutamide therapy when given to women for the treatment of AR(+), ER/PR(−) MBC. These circulating hormones require further evaluation for use as a pharmacodynamic marker. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-05-02.
PET/CT and MR Imaging of Central Nervous System Myelomatosis
Authors: Ba D. Nguyen, Panol C. Ram, Michael C. Roarke
Journal: Clinical Nuclear Medicine (2010)

Multiple myeloma essentially targets the axial and appendicular skeleton. From the skull and vertebra, the myelomatous lesions may extend to the brain and spinal canal. Extramedullary central nervous system involvement with leptomeningeal and epidural masses is uncommon and usually demonstrated by MR imaging in symptomatic patients. The authors present a case of clinically unexpected central nervous system myelomatosis initially detected by PET/CT and subsequently confirmed by MR.