tbuckley/cabot-search huggingface dataset:
PTH-067 Cost minimising introduction of wireless capsule endoscopy
Authors: J L Bacon, T Heymann
Journal: Gut (2010)

<h3>Introduction</h3> National Institute for Health and Clinical Excellence approved the use of relatively expensive capsule endoscopy (CE) to investigate mid gastrointestinal haemorrhage (MGIH) and small bowel Crohn9s disease (CD) in 2004. It gives a high diagnostic yield (31–76% MGIH, 43–71% CD), does not use radiation and causes few complications. In the past cheaper contrast fluoroscopy was the investigation of choice. Robust data that compare the two are limited. Which minimises costs when used in a public general hospital? <h3>Methods</h3> As part of our service audit we used electronic records to identify all patients who had had CE±fluoroscopy to investigate MGIB or CD at our institution from January 2007 to May 2008. (Patients referred from elsewhere for CE were excluded.) We established the indication for investigation, other tests that had been done and the positive diagnostic yield for each. We used activity based costing to determine procedure costs. We then constructed a cost minimising pathway for patient investigation for MGIB and CD and subjected our conclusions to sensitivity analyses. <h3>Results</h3> For CD investigation, 136 patients had fluoroscopy, 21 CE and 3 both. For MGIH 47 had fluoroscopy, 59 CE and 8 had both. The positive diagnostic yield for CD was 23% with fluoroscopy, approximate half that of CE (57%) and for MGIH, 2% with fluoroscopy and 56% with CE. Observation of actual practice suggests that both positive and negative fluoroscopy results may help clinicians conclude investigation of suspected CD in that few of the patients we studied had had both investigations. It appeared that the investigations in themselves were rarely definitive and were interpreted in the clinical context of individual patients. Relative costs for CE in the UK range from £1075 to 1368 and fluoroscopy £146–288. Fluoroscopy detects approximately half the CD cases that CE would at less than a quarter of the cost of CE. <h3>Conclusion</h3> To investigate CD, our analysis suggests that fluoroscopy should be used initially and only if negative and clinical suspicion of CD remains should CE then be done. The very low diagnostic yield for fluoroscopy vs. CE for MGIH demands that CE should be the imaging modality of choice and fluoroscopy abandoned as a diagnostic option. To determine the place for new, often expensive, investigation techniques cost minimisation analysis is effective. We estimate that, for our patient cohort, the use of CE as the first investigation for MGIH and only after a negative fluoroscopy study for suspected CD, our institution could have saved ∼£7000. Extrapolating these figures nationally the judicious use of CE has the potential to save the NHS £1.3 million per annum. The analysis does not factor in other CE benefits such as faster diagnosis of MGIH and less radiation exposure.
In vivo targeting of metastatic breast cancer via tumor vasculature-specific nano-graphene oxide
Authors: Dongzhi Yang, Liangzhu Feng, Casey A. Dougherty, Kathryn E. Luker, Daiqin Chen, Meagan A. Cauble, Mark M. Banaszak Holl, Gary D. Luker, Brian D. Ross, Zhuang Liu, Hao Hong
Journal: Biomaterials (2016)
Brugada Syndrome and the Subcutaneous Implantable Cardioverter-Defibrillator
Authors: Louise R.A. Olde Nordkamp, Giulio Conte, Boudewijn R.A.M. Rosenmöller, Joppe L.F. Warnaars, Hanno L. Tan, Maria L. Caputo, Francois Regoli, Tiziano Moccetti, Angelo Auricchio, Reinoud E. Knops, Arthur A.M. Wilde
Journal: Journal of the American College of Cardiology (2016)
Abstract 831: c-Myc is a novel target of prostate cancer cell growth inhibition by honokiol
Authors: Krishna B. Singh, Eun-Ryeong Hahm, Shivendra V. Singh
Journal: Cancer Research (2016)

Abstract Honokiol (HNK) has been shown to inhibit human prostate cancer cell growth in vitro and in vivo, but the underlying mechanism is not fully understood. The present study demonstrates that c-Myc, a key mediator of prostate cancer growth, is a novel target of HNK. Exposure of prostate cancer cells to plasma achievable concentrations of HNK resulted in a marked decrease in levels of total and/or phosphorylated c-Myc. HNK-mediated suppression of c-Myc protein level was due in part to repression of its transcription or protein degradation. We also observed down-regulation of c-Myc in tumors from PC-3 xenografted mice upon oral administration of HNK when compared with control; although the difference was not significant. Stable overexpression of c-Myc conferred protection against HNK-mediated inhibition of colony formation and G0-G1 cell cycle arrest in PC-3 cells. Moreover, HNK suppressed the expression of c-Myc downstream target genes (Cyclin D1 and EZH2) and these effects were restored in Myc-overexpressing PC-3 cells. Consistent with these results, cells with stable knockdown of EZH2 were more sensitive to growth inhibition by HNK compared with control cells. Because androgen receptor (AR) is implicated in regulation of c-Myc expression, we explored the possibility whether AR could affect the expression of c-Myc and its target genes. Indeed, AR overexpression in PC-3 cells enhanced the expression of both c-Myc and its target genes. In conclusion, it is reasonable to postulate that HNK may be effective in retarding growth of c-Myc-driven prostate cancer. This study was supported by the grants CA101753 and CA115498 awarded by the National Cancer Institute. Citation Format: Krishna B. Singh, Eun-Ryeong Hahm, Shivendra V. Singh. c-Myc is a novel target of prostate cancer cell growth inhibition by honokiol. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 831.
Clinical phase I/II study with the insulin-like growth factor-1 receptor inhibitor AXL1717: Future implications for patients with squamous non-small cell lung carcinoma?
Authors: S. Ekman, J. Frodin, J. Harmenberg, A. Bergman, A. Hedlund, P. Dahg, S. Bergstrom, M. Bergqvist
Journal: Journal of Clinical Oncology (2010)

e13019 Background: Inhibition of the insulin-like growth factor-1 receptor (IGF-1R) has resulted in extensive antitumor effects. AXL1717 is a small-molecule inhibitor of the IGF-1R without inhibition of closely related receptors including the insulin receptor and has shown extensive effects against a wide range of tumors in animals. Preclinical testing in two animal species showed excellent tolerability together with good oral bioavailability. Methods: AXL1717 is presently tested as an orally administrated single-agent treatment in an open-label phase I/II clinical study in advanced cancer patients with solid tumors that progress in spite of several lines of treatment. The first part (phase IA) consisted of single-day BID dosing every three weeks with consecutive dose escalations. The second part (phase IB) consists of 7 days or longer BID dosing every three weeks, dosing range being 520-700 mg BID. Nonprogressing patients could continue treatment within a compassionate use setting. Study objectives included identifying recommended phase II dose, pharmacokinetics, safety, and biological effects. The study followed GCP, was approved by Medical Product Agency and regional ERB. Results: The phase IA part of the study has successfully been concluded after 154 treatments given to 16 patients. The results show that AXL1717 can be administered as a single-day BID treatment in very high doses with excellent tolerability and good bioavailability. Dose-limiting toxicity has not been reported. Preliminary results from phase IB after 13 patients showed that AXL1717 can be given in multidose setting with good tolerability. Neutropenia was seen as dose-limiting toxicity at high exposure of the agent. Even though the study was not designed to show efficacy, 4/6 patients with squamous non-small cell lung cancer showed signs of tumor response including tumor necrosis on PET and prolonged stationary disease. Conclusions: This first clinical study of AXL1717 has shown that the agent can be administrated safely orally to advanced stage cancer patients resulting in good bioavailability and tolerability. Encouraging signs of tumor response were seen. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Axelar AB Axelar AB
Abstract 700: Regulation of Fn14 expression by EGFRvIII-STAT signaling enhances glioblastoma cell invasion and survival
Authors: Alison Roos, Zachary Mayo, Heather Sonnemann, Michael Pineda, Gil Lambert, Harshil D. Dhruv, Jeffrey A. Winkles, Michael E. Berens, Nhan L. Tran
Journal: Cancer Research (2016)

Abstract Glioblastoma Multiforme (GBM) is the most common malignant brain tumor in adults. Most GBM patients succumb to the disease less than one-year post diagnosis due to the highly invasive nature of the tumor, which prevents complete surgical resection and gives rise to tumor recurrence. The invasive phenotype also confers radio-and chemoresistant properties to the tumor cells; therefore, there is a need to develop new therapeutics that target drivers of GBM invasion. Amplification of EGFR is observed in over 50% of GBM tumors, of which half concurrently overexpress the variant EGFRvIII, and expression of both receptors confers a worse prognosis. EGFR and EGFRvIII cooperate to promote tumor progression and invasion, in part, through activation of the JAK/STAT-signaling pathway. Here we report that GBM cells expressing EGFRvIII show increased expression of a previously established mediator of glioma cell invasion and survival, fibroblast growth factor-inducible 14 (Fn14), at the mRNA and protein level. Treatment with STAT3, STAT5, JAK, or Src inhibitors decreased Fn14 mRNA and protein expression. Finally, knockdown of Fn14 levels in the EGFRvIII-expressing glioma cells decreased both cell survival after temozolomide (TMZ) treatment and cell invasion, which suggests that Fn14, in part, mediates the oncogenic phenotypes conferred by EGFRvIII signaling. Since EGFR inhibitors display limited therapeutic efficacy in GBM patients, we hypothesize that Fn14-targeted therapies could potentially limit invasiveness and chemoresistance in EGFRvIII-dependent GBM tumors. Citation Format: Alison Roos, Zachary Mayo, Heather Sonnemann, Michael Pineda, Gil Lambert, Harshil D. Dhruv, Jeffrey A. Winkles, Michael E. Berens, Nhan L. Tran. Regulation of Fn14 expression by EGFRvIII-STAT signaling enhances glioblastoma cell invasion and survival. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 700.
Outcome Of Patients With IPSS Intermediate (int) Or High Risk Myelodysplastic Syndrome (MDS) According To Donor Availability: A Multicenter Prospective Non Interventional Study For The SFGM-TC and GFM
Authors: Marie Robin, Raphael Porcher, Lionel Ades, Emmanuel Raffoux, Mauricette Michallet, Sylvie Francois, Jean-Yves Cahn, Alain Delmer, Stephane Vigouroux, Jacques-Olivier Bay, Jérôme Cornillon, Anne Huynh, Stephanie Nguyen, Laure Vincent, Natacha Maillard, Oumedaly Reman, Regis Peffault De Latour, Herve Dombret, Pierre Fenaux, Gérard Socié
Journal: Blood (2013)
Abstract 1834: Semaphorin 3C is an androgen receptor-regulated gene
Authors: Kevin J. Tam, Kush Dalal, Michael Hsing, Chi Wing Cheng, Yan Ting Chiang, Aishwariya Sharma, James W. Peacock, Artem Cherkasov, Yuzhuo Wang, Martin E. Gleave, Paul S. Rennie, Christopher J. Ong
Journal: Cancer Research (2016)

Abstract Prostate cancer (PCa) is the second leading cause of cancer-related deaths in North America. The androgen receptor (AR) is a member of the nuclear receptor superfamily of transcription factors and is heavily implicated in PCa progression. First-line therapies frequently target the AR axis and are initially met with favourable response but restored and aberrant AR signaling fuel disease progression to stages for which treatment is palliative. Transcriptional targets of the AR include genes involved in cell growth and cell fate but are not completely described. The semaphorin family of signaling proteins is a large grouping of cell-surface or secreted signaling proteins that function in neurogenesis and development. The roles of semaphorins in cancer are becoming increasingly evident however mechanistic details surrounding their involvement in cancer are poorly defined. One member of the class 3 semaphorins, SEMA3C, has been shown to confer invasive phenotypes in prostate cancer cells. Using the AR-positive LNCaP cell line we show that SEMA3C is an androgen-responsive gene. Additionally, using RSAT DNA analysis software we identify an androgen response element (ARE) in intron 2 of SEMA3C and show that AR is recruited to this genomic region in an androgen-dependent manner in chromatin immunoprecipitation assays. Furthermore, the isolated ARE binds to the AR-DNA binding domain in gel shift assays and can be transactivated by AR in reporter gene assays. Finally we show that the pioneering factor, GATA2, is necessary for AR-mediated expression of SEMA3C. Collectively, our work identifies SEMA3C as a direct transcriptional target of AR in support of our hypothesis that dysregulated AR signaling drives inadvertent upregulation of SEMA3C and PCa disease progression. Deregulated AR signaling underpins prostate cancer progression and underscores the need to elucidate transcriptional targets of AR. Identification of SEMA3C as a novel target of AR provides the rationale for targeted therapies directed against SEMA3C. Citation Format: Kevin J. Tam, Kush Dalal, Michael Hsing, Chi Wing Cheng, Yan Ting Chiang, Aishwariya Sharma, James W. Peacock, Artem Cherkasov, Yuzhuo Wang, Martin E. Gleave, Paul S. Rennie, Christopher J. Ong. Semaphorin 3C is an androgen receptor-regulated gene. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1834.
Loading of tacrolimus containing lipid based drug delivery systems into mesoporous silica for extended release
Authors: Li Liu, Jia Li, Mei-hui Zhao, Hui Xu, Lin-sen Li, Shao-ning Wang
Journal: Asian Journal of Pharmaceutical Sciences (2016)

Many studies had been focused on designing tacrolimus sustained release preparations based on solid dispersion technique, but no one had tried to employ mesoporous silica as the carrier material to realize this goal. The purpose of this study was to develop a novel, simple and environmental friendly drug loading method with mesoporous silica to obtain tacrolimus sustained-release preparation. Tacrolimus was firstly dissolved in the molten mixed lipid composed of Compritol 888 ATO and Gelucire 50/13 to prepare a drug loaded lipid-based drug delivery systems (LBDDS), then the liquid LBDDS was adsorbed by mesoporous silica to transfer the liquid into solid powder, ie. the tacrolimus sustained release silica-lipid hybrid (SLH). The SLH was characterized by SEM, CLSM, XRPD and DSC, and the in vitro drug release was tested using a paddle method. SEM and CLSM observation showed that the LBDDS was efficiently distributed throughout the pores of the silica. The results of DSC and XRPD illustrated that the lipid existed inside the silica at amorphous state. The drug-loaded SLH showed good flowability, compressibility, compactibilty and two-phase in vitro drug release process within 24 hours, which did not change obviously even after storage at 40 °C for 10 d. The present study provided a novel and simple method to prepare tacrolimus sustained release powder, which provided a feasible solution to solidify the liquid LBDDS of not only extended drug release behavior, but also improved stability and micromeritic properties.
Consensus Report of the 2015 Weinman International Conference on Mesothelioma
Authors: Michele Carbone, Shreya Kanodia, Ann Chao, Aubrey Miller, Anil Wali, David Weissman, Alex Adjei, Francine Baumann, Paolo Boffetta, Brenda Buck, Marc de Perrot, A. Umran Dogan, Steve Gavett, Alessandro Gualtieri, Raffit Hassan, Mary Hesdorffer, Fred R. Hirsch, David Larson, Weimin Mao, Scott Masten, Harvey I. Pass, Julian Peto, Enrico Pira, Ian Steele, Anne Tsao, Gavitt Alida Woodard, Haining Yang, Shakun Malik
Journal: Journal of Thoracic Oncology (2016)
ECG Challenge: March 15, 2016
Authors: Philip Podrid
Journal: Circulation (2016)

ECG Challenge 1131A 74-year-old man with a history of hypertension and hypertensive heart disease, taking lisinopril, hydrochlorothiazide, and a β-blocker, presents to his primary care physician for a routine physical examination.He has no symptoms.His blood pressure is 190/100 mm Hg, and the rest of the physical examination is unremarkable.An ECG is obtained (ECG A).The patient is sent to the emergency department where his blood pressure is still elevated.An ECG is repeated (ECG B). What is the diagnosis?The diagnosis will follow in next week's issue (March 22).
COMBINATION Antifungal THERAPY for Proven and Probable Invasive Fungal INFECTION IN HIGHLY Immunocompromised Patients.
Authors: R. Rojas, Jr Molina, I. Jarque, C. Montes, J. Besalduch, D. Rubio, E. Carreras, L. Madero, E. Conde, MA Sanz, Antonio P. Torres Gomez
Journal: Blood (2009)
Oral vitamin K did not reduce bleeding in patients with excessive anticoagulation after receiving warfarin
Authors: Matthew Rondina
Journal: Annals of Internal Medicine (2009)

Source Citation Crowther MA, Ageno W, Garcia D, et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med. 2009;150:293-300. 19258557
Abstract 303: Compensatory up-regulation of NEK9 contributes to resistance to PLK1 inhibition in triple-negative breast cancer cells
Authors: Nelson K. Y. Wong, Devon Mitchell, Mohamed K. Khan
Journal: Cancer Research (2016)

Abstract Patients with triple-negative breast cancers (TNBCs) have very poor prognosis in terms of relapse and overall survival. There is currently no targeted therapy for this heterogeneous group of patients and it presents a pressing unmet medical need. Recent data suggest that Polo-like kinase 1 (PLK1) is a plausible target for treating TNBCs, and many small-molecule inhibitors are currently under development for targeting this kinase. Since clinical data have shown that single-agent treatment often leads to resistance and relapse of the cancer, it is essential to identify potential resistance mechanisms of TNBCs to PLK1 inhibition such that combination therapy can be rationally designed to increase treatment efficacy. We have selected ten individual cell clones from a TNBC cell line, MDA-MB-231, through long-term incubation of the cells with increasing concentrations of a PLK1 inhibitor BI 2536. We hypothesized that increased expression and/or activities of other kinases can compensate for the PLK1 inhibition. To identify these kinases, we screened the expression levels of &amp;gt;500 human kinases in the resistant clones in comparison to the parental cells, using the Nanostring platform, and generated a list of candidate kinases. Among the candidates, NEK9, a downstream effector of PLK1, was confirmed to be over-expressed in all resistant cell clones through Western blotting. MDA-MB-231 parental cells were then infected with a lentiviral over-expression vector that contains NEK9 and GFP. When a mixed population of NEK9-over-expressing cells (GFP+) and parental cells (GFP-) were incubated in the presence of BI 2536, increased proportion of GFP+ cells and increased mean GFP fluorescence intensity was observed over time through flow cytometry. Increase of NEK9 expression was also confirmed with Western blotting in the mixed cell culture experiment, indicating the selection of the NEK9-over-expressing cells in the presence of BI 2536. In conclusion, we have constructed a list of over-expressed kinase candidates that may contribute to the resistance to PLK1 inhibition. We further identify that over-expression of NEK9 contributes to the resistance phenotype. Our data prompt the need to further study the biology around NEK9 and suggest the possibility of combination therapy through inhibition of PLK1 and NEK9 in treating TNBCs. Citation Format: Nelson K. Y. Wong, Devon Mitchell, Mohamed K. Khan. Compensatory up-regulation of NEK9 contributes to resistance to PLK1 inhibition in triple-negative breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 303.
ADAM17 is a Tumor Promoter and Therapeutic Target in Western Diet–associated Colon Cancer
Authors: Reba Mustafi, Urszula Dougherty, Devkumar Mustafi, Fatma Ayaloglu-Butun, Michelle Fletcher, Sarbani Adhikari, Farhana Sadiq, Katherine Meckel, Haider I. Haider, Abdurahman Khalil, Joel Pekow, Vani Konda, Loren Joseph, John Hart, Alessandro Fichera, Yan Chun Li, Marc Bissonnette
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Epidermal growth factor receptors (EGFR) are required for tumor promotion by Western diet. The metalloprotease, ADAM17 activates EGFR by releasing pro-EGFR ligands. ADAM17 is regulated by G-protein–coupled receptors, including CXCR4. Here we investigated CXCR4–ADAM17 crosstalk and examined the role of ADAM17 in tumorigenesis. Experimental Design: We used CXCR4 inhibitor, AMD3100 and ADAM17 inhibitor, BMS566394 to assess CXCR4–ADAM17 crosstalk in colon cancer cells. We compared the expression of CXCR4 ligand, CXCL2, and ADAM17 in mice fed Western diet versus standard diet. Separately, mice were treated with marimastat, a broad-spectrum ADAM17 inhibitor, or AMD3100 to assess EGFR activation by ADAM17 and CXCR4. Using Apc-mutant Min mice, we investigated the effects of ADAM17/10 inhibitor INCB3619 on tumorigenesis. To assess the effects of colonocyte ADAM17, mice with ADAM17 conditional deletion were treated with azoxymethane (AOM). ADAM17 expression was also compared in colonocytes from primary human colon cancers and adjacent mucosa. Results: CXCL12 treatment activated colon cancer cell EGFR signals, and CXCR4 or ADAM17 blockade reduced this activation. In vivo, Western diet increased CXCL12 in stromal cells and TGFα in colonocytes. Marimastat or AMD3100 caused &amp;gt;50% reduction in EGFR signals (P &amp;lt; 0.05). In Min mice, INCB3619 reduced EGFR signals in adenomas and inhibited intestinal tumor multiplicity (P &amp;lt; 0.05). In the AOM model, colonocyte ADAM17 deletion reduced EGFR signals and colonic tumor development (P &amp;lt; 0.05). Finally, ADAM17 was upregulated &amp;gt;2.5-fold in human malignant colonocytes. Conclusions: ADAM17 is a Western diet–inducible enzyme activated by CXCL12–CXCR4 signaling, suggesting the pathway: Western diet→CXCL12→CXCR4→ADAM17→TGFα→EGFR. ADAM17 might serve as a druggable target in chemoprevention strategies. Clin Cancer Res; 23(2); 549–61. ©2016 AACR.
Hepcidin and GDF15 Levels during the First 2 Years Follow-up in Patients with Low and Int-1 Risk Myelodysplastic Syndromes (MDS) from the European Leukemianet MDS Registry
Authors: Louise De Swart, Chloé Reiniers, Tim Bagguley, Corine van Marrewijk, David Bowen, Jaroslav Cermak, Eva Hellström-Lindberg, Aurelia Tatic, Argiris Symeonidis, Gerwin A Huls, Alex Smith, Theo de Witte
Journal: Blood (2014)
High Dose Intensive Chemotherapy, as Is Standard in Childhood Leukemia, Is Feasible and Efficacious in Adult Patients with Acute Lymphoblastic Leukemia (ALL) up to the Age of 40
Authors: A. W. Rijneveld, B. van der Holt, Simon Daenen, B. J. Biemond, A. A. van de Loosdrecht, O. de Weerdt, P. Muus, J. Maertens, V. Mattijssen, H. Demuynck, Mcjc Legdeur, P. W. Wijermans, S. Wittebol, F. Spoelstra, A. W. Dekker, G. J. Ossenkoppele, J. J. Cornelissen, R. Willemze
Journal: Blood (2009)