tbuckley/cabot-search huggingface dataset:
Abstract 5387: Prostate-targeted radiosensitization via aptamer-shRNA chimeras
Authors: Xiaohua Ni, Yonggang Zhang, Judit Ribas, Wasim H. Chodhury, Mark Castanares, Zhewei Zhang, Marikki Laiho, Theodore L. DeWeese, Shawn E. Lupold
Journal: Cancer Research (2011)

Abstract Dose-escalated radiation therapy for localized prostate cancer (PCa) has a clear therapeutic benefit; however, escalated doses may also increase injury to non-cancerous tissues. Radiation-sensitizing agents can improve ionizing radiation (IR) potency, but without targeted delivery these agents will also sensitize surrounding normal tissues. Here we describe the development and application of prostate-targeted RNA interference agents which selectively sensitize PSMA-positive cells to IR. A high throughput siRNA screen identified DNA-PK, MAD2L2, BRCA2, NBN, RAD23B, and RAD54L as candidate DNA-repair pathway targets for prostate cancer radio-sensitization. When candidate shRNAs were conjugated to the PSMA-targeting RNA aptamer, A10-3, they were selectively delivered into PSMA positive prostate cancer cells in the absence of traditional transfection reagents. The shRNA portion was then processed by dicer to the corresponding siRNA. DNA-PK shRNAs, delivered by PSMA-targeting RNA aptamers, selectively reduced DNA-PK in PCa cells, xenografts and human prostate tissues. The mechanism of DNA-PK knock-down was confirmed to be through RNA interference by 5’-RACE assay. In tumor injection models A10-3-DNA-PK-shRNAs, combined with IR, dramatically and specifically enhanced PSMA-positive tumor response to IR. This treatment extended time to reach quadruple tumor volume by approximately 10 weeks when compared to only one week in tumors treated with radiation and control aptamer-shRNAs. A10-3-DNA-PK-shRNA and radiation had no affect on the PSMA negative PC-3 tumors. These studies support aptamer-shRNAs as selective sensitizing agents which may improve the treatment of high-risk localized PCa. 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 5387. doi:10.1158/1538-7445.AM2011-5387
Immune Status of Children One to Four Years of Age as Determined by History and Antibody Measurement
Authors: Eli Gold, Alfred Fevrier, Milford H. Hatch, Kenneth L. Herrmann, Wallis L. Jones, Richard D. Krugman, Paul D. Parkman
Journal: New England Journal of Medicine (1973)

Measurement of serum antibody levels in children one to four years old, living in three city and one suburban census tract, revealed that 63 per cent of the total study population were susceptible to rubella and approximately 33 per cent had inadequate titers of measles antibody. Antitoxin levels to diphtheria and tetanus were low in 24 and 7 per cent respectively of the entire study group. A large proportion (57 per cent) of these children had serum antibody levels of less than 10 to one or more types of poliovirus. Many had low antibody levels after the recommended number of immunizations; others had not received adequate poliomyelitis vaccine. Although those with low levels may not contract paralytic disease, if reinfected with wild poliovirus, they may spread the infectious agent to susceptible persons in the environment. Increased effort should be made to immunize all preschool children. Advisory committees should consider the need for periodic reimmunization. (N Engl J Med 289:231–235, 1973)
Abstract 1497: Matrix metalloproteinase-9 mediates growth, invasion, and metastasis of human breast cancer cells
Authors: Christine Mehner, Erin Miller, Derek C. Radisky, Evette S. Radisky
Journal: Cancer Research (2011)

Abstract Most breast cancer deaths are the consequence of metastasis from the primary site. In order to metastasize, tumor cells must escape the physical barriers that contain the growing primary tumor, enter the vascular system, exit the vascular system at a distant point, and colonize a distant organ. An important mediator of metastasis is matrix metalloproteinase-9, a member of the MMP family that has been found to be upregulated both in breast cancer cells and in the surrounding tumor stroma. Studies using animal models have sometimes produced apparently contradictory findings, due in part to methodology in which MMP-9 expression is suppressed throughout the host organism and throughout the course of tumor initiation and progression. To define the specific role of tumor cell-produced MMP-9 in metastasis of human breast cancer, we implemented a bioluminescent imaging animal model of metastasis in which luciferase-expressing MDA-MB-231 cells, infected either with control nontarget lentivirus (MDA-MB-231-NT) or with shRNA lentivirus targeting MMP-9 (MDA-MB-231-MMP9-KD), were orthotopically implanted into the mammary fat pads of immunocompromised mice. Tumor growth and development of lung metastases were assessed over 10 weeks using an IVIS imager. At 11 weeks mice were sacrificed, and tumor progression was assessed by ex vivo lung imaging and by immunohistochemical processing of the tumors and the lungs. Imaging studies revealed that primary tumors developing from MMP-9 knockdown cells grew more slowly throughout the course of the study (ranging from 25% to 50%), and that while the majority of the control group developed lung metastases, none of the mice injected with MDA-MB-231-MMP9-KD cells showed metastatic progression. After sacrifice, the measured tumor weight showed a median of 99 mg for the MDA-MB-231-MMP9-KD and 158 mg for the MDA-MB-231-NT tumors, showing that knockdown of MMP-9 inhibited tumor growth. Ex vivo imaging of the lungs confirmed the in vivo studies: no metastases were detected from MDA-MB-231-MMP9-KD cells, while all lungs of the MDA-MB-231-NT injected mice had detectable metastases (p=0.0079). Similarly, a single level immunohistochemical correlate found no metastases in the MDA-MB-231-MMP9-KD mice, while 3 of 4 mice with the non-target control cells showed large metastases (median 7×103 μm2). Our results demonstrate that expression of MMP-9 by human breast cancer cells plays a significant role in the progression of tumor growth and metastasis and provide insight into the potential of MMP-9 as a target for therapeutic intervention. 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 1497. doi:10.1158/1538-7445.AM2011-1497
NT-34 * COMPLETE RESPONSE TO VEMURAFINIB IN A PATIENT WITH METASTATIC ANAPLASTIC XANTHROASTROCYTOMA
Authors: R. Thomas, A. Ajlan, J. Ziskin, S. Soltys, S. Reddy, L. Recht, S. Nagpal
Journal: Neuro-Oncology (2014)

INTRODUCTION: Approximately 70% of pleomorphic xanthroastrocytomas(PXA) harbor the BRAF-V600E mutation.Vemurafinib has demonstrated activity in melanoma patients with the mutation, but variable activity in other tumors. We report complete response to vemurafanib in a patient with metastatic, anaplastic PXA. CASE: A 38 year old man presented with four weeks of visual disturbance. He underwent complete resection of a left occipital anaplastic PXA, BRAF-V600E mutated. Re-resection was performed one month later for local recurrence with new dural-based disease. Concern for leptomeningeal disease prompted cranio-spinal irradiation. Mid-treatment MRI demonstrated in-field growth of dural nodules and bony invasion. Simultaneously, he developed dyspnea due to bilateral pleural effusions and lung nodules. Biopsy of nodules and effusion revealed a BRAF-V600E mutated neoplasm, confirming metastatic disease. Vemurafinib was initiated, with almost immediate relief of dyspnea. Now, three months later, the patient has no detectable disease. DISCUSSION: Though the response to vemurafinib in primary CNS neoplasms has been modest, this case suggests rapid and complete response is possible. It also supports the argument for early BRAF-V600E testing in glial tumors.
Treatment of Primary Erythromelalgia with Cyclosporine
Authors: Shigetoshi Sano, Satoshi Itami, Kunihiko Yoshikawa
Journal: New England Journal of Medicine (2003)

To the Editor: Erythromelalgia is a rare disease of unknown cause, characterized by redness of the skin, increased temperature, and pain in the extremities. Erythromelalgia is often primary, but it may also be secondary to disorders such as myeloproliferative diseases. Although a wide variety of therapies have been tried, no effective treatment is yet available. A 28-year-old woman presented with severe, persistent burning pain in the legs and feet, with marked erythema, swelling, and warmth (Figure 1, left-hand panels). The erythema had begun at the age of four years, with no associated disorder. After adolescence, the symptoms became continuous, with . . .
Diagnostic accuracy and clinical utility of K-ras mutation analysis on FNA aspirates of pancreatic masses under EUS guidance
Authors: C De Angelis, M Goss, P Allegranza, F Brizzi, D Reggio, L Daniele, D Pacchioni, S Mariani, M Bruno, P Carucci, M Rizzetto
Journal: Endoscopy (2011)

Introduction/Objectives: Cytological analysis on specimen obtained by Endoscopic Ultrasound-Fine NeedleAspiration (EUS-FNA) is known as the most accurate technique for the diagnosis of pancreatic adenocarcinoma. Nonetheless, differenzial diagnosis between adenocarcinoma and other pseudotumoral lesions (such as chronic pancreatitis) can be challenging. Almost all pancreatic adenocarcinomas show mutational activation of K-ras oncogene. Analysis of mutations of K-ras on aspirates provided by EUS-FNA could be a helpful method to distinguish neoplasia from benign lesions.
Hypokalemic Myopathy with Myoglobinuria Associated with Licorice Ingestion
Authors: Elliott G. Gross, James D. Dexter, Robert G. Roth
Journal: New England Journal of Medicine (1966)

THE causes of potassium depletion1 which may lead to myopathy include endogenous or exogenous adrenal hypercorticism, excessive gastrointestinal-fluid losses, kaliuretic agents, Fanconi syndrome2 and other renal tubular defects.3 , 4 The kaliuretic effect of licorice is a less well known cause of potassium depletion.5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Myoglobinuria has been reported to occur in patients with extensive trauma or ischemia of striated muscle, idiopathic recurrent rhabdomyolysis, myopathies due to abnormal glycolysis21 22 and various primary diseases of muscle. It has also been reported in a patient with regional enteritis in whom severe hypokalemia developed during treatment with steroids.23 Myoglobinuria has been reviewed by Hed24 and recently . . .
Abstract 5117: PKD1 suppresses filopodia formation and increases LIM Kinase 1 expression in prostate cancer cells
Authors: Md. Helal U. Biswas, Cheng Du, Chuanyou Zhang, K.C. Balaji
Journal: Cancer Research (2010)

Abstract Introduction: We have previously demonstrated that transfection of PKD1 into highly metastatic C4-2 prostate cancer cells decreased cell motility. Filopodia are thin, actin-rich plasma-membrane protrusion that have an important role in cell motility and wound healing. Moreover, the initiation and elongation of filopodia depend on the precisely regulated polymerization, convergence and cross linking of actin filaments that are dynamically regulated by a variety of actin-binding proteins including Cofilin. However, Cofilin is inactivated by phosphorylation through the LIM kinase1 (LIMK1), a LIM-domain containing serine-threonine-tyrosine kinase, and activated by dephosphorylation through the Slingshot protein. In this study, we explored that PKD1 increased LIMK1 expression and suppressed filopodia formation with consequent effects on cell motility. Methods: Phosphorylation of Cofilin as well as expression of GFP, PKD1-GFP and LIMK1 was confirmed by western blot analysis. Filopodia formation was detected by phalloidine staining. Wound healing assay was performed for evaluating the cell motility. Results: To find out the role of PKD1 in LIMK1 regulation, we overexpressed PKD1 in PC3 cells followed by stimulation with phorbol 12-myristate 13-acetate (PMA) or Bryostatin-1, a PKD1 selective activator, and observed that the expression of LIMK1 was increased in dose dependent fashion compared to control. We also observed the phosphorylation of Cofilin was increased in PKD1 over expressing cells stimulated with PMA and Bryostatin-1 but not in control cells. Additionally, a number of filopodia were present in every GFP over expressing PC3 cells, whereas were completely absent in PKD1 over expressing PC3 cells. In addition, wound healing assay demonstrated that cell motility was suppressed by PKD1 over expression in PC cells compared to control. Conclusions: Our data shows for first time that PKD1 modulates filopodia formation with increased expression of LIMK1 in PC cells. Additionally, we also found that PKD1 suppressed cell motility with regulation of Cofilin function that might play a role in suppression of metastasis. PKD1 suppressed filopodia formation by modulating LIMK1 expression a novel mechanism leading to altered motility in PC cells. 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 5117.
P115 Evidence Of Post-code Lottery In The Availability Of Pulmonary Rehabilitation (pr) In The East Of England (eoe)
Authors: L. Jongepier, R. Barlow
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> Pulmonary Rehabilitation (PR) should be made available to all suitable people with COPDand various other chronic respiratory conditions.<sup>1</sup> Recommendations have been made on the quality of the provision and commissioning of PR. Indicative benchmark rates have been developed<sup>2 </sup>to support commissioners determine local need. We compared the local availability of PR across the EoE. <h3>Methods</h3> A regional PR group was formed to promote best practice, offer peer support and enable improvements through the collection of meaningful regional data. Data was collected from 17/18 (94%) providers on the number of PR places commissioned per CCG(s). In 13 providers PR was commissioned. In 4 providers PR was provided under Payment by Result and in these maximum capacity was calculated using a 1:8 staff:patient ratio. Comparison was made between availability and indicative benchmark rates in each locality. Where providers covered more than one CCG, data was aggregated for analysis purposes. <h3>Results</h3> In the EoE the average number of people expected to benefit from PR/year is 11,748 (192 per 100,000 population/year).<sup>3</sup> However, our data showed a maximum of 6,165 PR places were available (101 per 100,000/year). Local provision varied 2.8-fold across the CCGs, ranging between 60 per 100,000/year and 171 per 100,000/year. This was not explained by local variation based on local need as actual provision/local target varied 3.1-fold [27.2%-85.4%]. <h3>Conclusions</h3> There was evidence of post-code lottery in the provision of PR with a 2.8-fold variation between localities. There was also an overall insufficient availability throughout the region (average 52.5% of the proposed target). Provision compared to local targets varied more than 3-fold. Provision was less than 50% of local target in 50% of localities. This data will be shared with local commissioners and providers, so that this deficiency can be addressed. <h3>References</h3> National Institute for Health and Clinical Excellence (NICE). COPD: management of COPD in adults in primary and secondary care. 2010 http://www.nice.org.uk/guidance/CG101 National Institute for Health and Clinical Excellence (NICE). Commissioning Guides: Services for people with COPD[http://publications.nice.org.uk/services-for-people-with-chronic-obstructive-pulmonary-disease-cmg43/44-commissioning-high-quality-integrated-care-for-people-with-copd] Accessed on 05/07/14 East of England Commissioning Framework 10/11.[http://www.ibyd.co.uk/bhf/documents/Strategic_Health_Authorities/East/CommissioningFramework1011.pdf] Accessed 04/07/14
Quantitative assessment of liver function (QLF) in the early diagnosis of acute graft failure (AGF) following orthotopic liver transplantation (OLT)
Authors: R.M. Iemmolo, L. Fabrie, R. Merenda, D. Neri, F. Paleari, M.T. Vilei, G.E. Gerunds, A. Maffei Faccioli, L. Okoliceanyi
Journal: Journal of Hepatology (1991)
Abstract LB-383: <i>In vitro</i> and <i>in vivo</i> MRI evaluation of a novel metallofullerene nanoparticle
Authors: Pavan P. Adiseshaiah, Stephen T. Stern, Lilia Ileva, Robert Lenk, Darren Macfarland, Chris L. Kepley, Scott E. McNeil
Journal: Cancer Research (2010)

Abstract Some disadvantages of conventional small molecule contrast agents, such as Magnevist® (Gd - DTPA), are that they extravasate rapidly and are quickly eliminated from blood, limiting the viable MRI time. Macromolecular magnetic resonance imaging (MRI) contrast agents, on the other hand, are useful blood-pool agents and have found application in monitoring tumor vasculature and angiogenesis. There is an urgent need for new MRI contrast agents with higher relaxivity and longer blood half-life. Here, we report in vitro and in vivo characterization of a water-soluble derivatized fullerene nanoparticle contrast agent (NCL124) in comparison to the market standard, Magnevist. In comparison to Magnevist, NCL124 had higher R1and R2 relaxivities in human plasma at 22° C and 37°C. In vivo MRI imaging was performed on a LS174T dual-flank xenografts following a single intravenous injection of NCL 124 or Magnevist contrast agent (0.2 mmol Gd/Kg) using a 3.0 Tesla clinical whole-body MRI. Based on the relaxivity-time profiles, the Vss for NCL124 was similar to that of albumin (∼ 100 mL/Kg), suggesting high protein binding, while the Vss of Magnevist was similar to that of extracellular tissue water (∼200 mL/Kg), as expected for an extracellular diffusible tracer. NCL124 also had a longer blood half-life (∼ 100 min) than Magnevist (19 min). Taken together, the higher concentration (Cmax) and exposure (AUCall) of NCL124 in the blood, coupled with slow elimination, supports the use of NCL124 as a blood-pool contrast agent. Intriguingly, the half-life of NCL124 varied by tumor size, while Magnevist showed similar half-life in both tumors. This suggests NCL124 may have significant utility in predicting differences in tumor vascular and lymphatic permeability, and potentially be useful as a marker for antiangiogenic therapy. Funded by NCI contract # HHSN261200800001E. 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 LB-383.
What's in a name?
Authors: R. Day
Journal: BMJ (2001)

GMC: approaching the abyss Preservation is well worth the effortEditor-In his editorial on the General Medical Council, Smith asks a question that is in danger of becoming a self fulfilling prophecy. 1He fairly describes differences of view in the British medical profession about governance and the introduction of revalidation.He then asks whether it is worth expending the effort required to ensure the GMC's survival on the grounds of its being dysfunctional, even suggesting that it might be better to scrap it and start again.We write as a disparate group of senior doctors who have been intimately involved in the debate on the future of the GMC.We have held differing views about the solutions that might be offered but are united on the over-riding importance of professionally led regulation in partnership with the public.In this, we concur with Smith that most doctors wish to practise to the highest possible standards and that the model of the intrusive regulatory scrutiny practised by casino operators is totally inappropriate to the medical profession.We believe, from very different perspectives, that the GMC should be allowed to develop into a better organisation for doctors and, more importantly, for patients.Smith's implication that we should start looking at fresh alternatives begs the question as to who would be entrusted do this work and whether the result would be any better equipped for the challenges faced by a 21st century regulator in an increasingly complicated society.Any "fresh start" would still have to deal with governance and revalidation, which have been firmly placed on the current agenda by the present GMC.The abyss Smith describes is certainly there, and the GMC may be at its edge.Despite its current problems, however, the GMC is the crucible of our professionalism and without it doctors in this country would become mere technicians.Any alternative to professionally led regulation is unthinkable.
Evaluation of subepithelial lesion of the appendix by endoscopic ultrasound
Authors: Lee Tae Hee
Journal: Endoscopy (2011)

Background: The use of through-the-scope (TTS) miniprobe catheter endoscopic ultrasound is a valuable technique for evaluating subepithelial lesions in the proximal colon. Few reports include the evaluation of the appendix by EUS.
Incidence and aetiology of acute injuries during competitive road cycling
Authors: Mathieu Decock, Lieven De Wilde, Luc Vanden Bossche, Adelheid Steyaert, Alexander Van Tongel
Journal: British Journal of Sports Medicine (2016)

Despite the ever-increasing popularity of bicycle racing, the high perceived risk of acute injuries and the recent media attention, studies of acute injuries in road cyclists are rather scarce. The goal of this study is to evaluate the incidence, aetiology and patterns of acute injuries in non-professional competitive road cyclists during cycling races in Flanders.All acute injuries that occurred during competition in Flanders in 2002 and 2012, collected in the injury registry, were analysed. The incidence, injury rate, diagnosis, circumstances and level of performance were evaluated.A total of 777 documented reports of accidents (1230 injuries) were retrieved for the years 2002 and 2012. There was no significant difference between incidence and injury rate between 2002 and 2012. There was a strong significant difference in the incidence between the different levels of performance in both seasons. Severe injuries were seen in 29.5% in 2002 and in 30.1% in 2012. The most common location of a severe injury was the hand. Collision with another rider was the most common cause of injury.Almost 1 out of 6 non-professional competitive road cyclists had an accident during cycling races in 2002 and 2012 in Flanders and collision with other riders was the most important cause of a crash. The most common lesion was abrasion, but almost one out of three riders had a severe injury.