tbuckley/cabot-search huggingface dataset:
Abstract 1374: Cross-resistance and sensitivity of sunitinib resistant tumor cells
Authors: Kristy J. Gotink, Henk J. Broxterman, Richard R. de Haas, Maria N. Rovithi, Roberto Pili, Henk MW Verheul
Journal: Cancer Research (2012)

Abstract Background: Resistance to sunitinib, a multi-targeted anti-angiogenic tyrosine kinase inhibitor (TKI) approved for clinical use in advanced renal cell cancer, gastrointestinal stromal tumors and pancreatic neuroendocrine tumors, represents a major clinical problem. Previously we have shown that tumor cells acquire resistance in vitro by continuous incubation with sunitinib and found that acidic lysosomal sequestration of sunitinib mediates its resistance. In this study, we investigated whether sunitinib resistant tumor cells are cross-resistant to other clinically relevant inhibitors and whether agents interfering with lysosomal function can modulate resistance. Methods: Continuous exposure to sunitinib for more than 12 months resulted in drug resistance in 786-O (RCC) and HT-29 (colorectal cancer) cell lines. Using these cells, cross-resistance to other clinically available TKIs such as sorafenib, pazopanib and erlotinib, and to the mTOR inhibitor everolimus, was determined in proliferation assays (MTT). In addition, modulation of sunitinib resistance by the lysosomal inhibitors (LIs) chloroquine and bafilomycin A1 was studied using proliferation assays. The effect of LIs on phosphorylation of key signaling proteins was determined by western blotting. Results: Compared to parental cell lines, proliferation assays revealed that sunitinib resistant cell lines were cross-resistant to pazopanib and erlotinib, while no significant decrease in sensitivity to sorafenib or everolimus was observed. Both chloroquine and bafilomycin A1 were able to modulate sunitinib resistance. Western blot analysis revealed that phosphorylation of key signaling proteins including Akt and p44/42-MAPK was inhibited in sunitinib resistant cells upon co-incubation with chloroquine, while sunitinib alone did not inhibit phosphorylation of these kinases. Conclusion: We found that sunitinib resistant tumor cells are cross-resistant to pazopanib and erlotinib, but remain sensitive to sorafenib and everolimus. Furthermore, combination with the lysosomal inhibitor chloroquine resulted in inhibition of key signaling proteins in sunitinib resistant cells. Taken together, we envision that these findings are relevant for clinical treatment strategies in patients with renal cell cancer resistant to sunitinib. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1374. doi:1538-7445.AM2012-1374
The Role of the Obstetrician in the Prevention of Cervical Cancer
Authors: Lorna D. Johnson
Journal: New England Journal of Medicine (1960)

FOR the past ten years there has been an increasing interest in the concept that invasive carcinoma of the cervix is preceded by an in situ stage that has all the morphologic properties of cancer except invasion of the stroma. Furthermore, there is evidence that carcinoma in situ does not arise de novo, but is preceded by recognizable cytologic and morphologic changes variously described as epithelial anaplasia, dysplasia, atypia or equivocal lesions.1 2 3 4 The immense importance of this concept lies in the implication that if these changes are progressive then their eradication constitutes a method of prevention of frank invasive cancer. . . .
Working together to improve the credibility and transparency of clinical research
Authors: P. Mosconi, A. Roberto
Journal: BMJ (2013)

Jones and colleagues’ article is important for the scientific community as well as consumers and patients.1 For patients who give their informed consent to enter a randomised clinical trial it is difficult to accept that a large proportion (29%) of clinical trial results are not published and will not be available for clinical practice and further research. All …
False-Positive Radioiodine Uptake in the Abdomen and the Pelvis:
Authors: Siema Mb Bakheet, Muhammad M Hammami, John Powe
Journal: Clinical Nuclear Medicine (1996)

Because the kidneys are usually not visualized on radioiodine whole-body scans, the renal uptake can be mistaken for a thyroid cancer metastasis. The authors report the prevalence and characteristics of radioiodine retention in the kidneys and review the reported causes of false-positive radioiodine uptake in the abdomen and pelvic areas. Radioiodine uptake in the renal bed was noted on 9 of 400 (2.2%) I-123 diagnostic whole-body scans performed over a 7-month period in our center. The uptake was noted more clearly on posterior views, cleared on delayed images after further hydration, and was not consistently present on follow-up scans. It was unilateral and mimicked a renal or adrenal metastasis in 44% of the scans. In three cases, the uptake was associated with a dilated calyx, an extrarenal pelvis, or a voluminous pelvis. False-positive radioiodine uptake in the abdomen and pelvis has been previously reported in association with 14 different conditions. However, renal retention may represent the most common cause of false-positive radioiodine uptake in the abdomen pelvis. Delayed imaging after additional hydration is usually sufficient to clarify its origin.
CORRELATION OF SCAR LOCALIZATION BETWEEN CARDIAC MAGNETIC RESONANCE IMAGING AND ELECTRO-ANATOMIC MAPPING AT ELECTROPHYSIOLOGY STUDY IN PATIENTS WITH CARDIAC RHYTHM MANAGEMENT DEVICES
Authors: Rajeev Fernando, Nisreen F. Ali, Lara Bakhos, Jeffrey Winterfield, David Wilber, Osamah Abdallah, Mark Rabbat, Mushabbar Syed
Journal: Journal of the American College of Cardiology (2015)
Ophthalmic Manifestations of the Carcinoid Flush
Authors: Vernon G. Wong, Kenneth L. Melmon
Journal: New England Journal of Medicine (1967)

WE recently recognized distinctive ophthalmic consequences of the carcinoid syndrome that have not been reported. Patients with malignant carcinoid were studied during their hospital courses at the National Institutes of Health. Their ocular changes form the basis of this report.Material and MethodsThe subjects were 16 patients from thirty-three to sixty-nine years old. The diagnosis of carcinoid tumor was established histologically by biopsy, pharmacologically by flushes induced with epinephrine1 2 3 and chemically by the demonstration of abnormally large concentrations of serotonin (5-hydroxytryptamine) in platelets and of 5-hydroxyindoleacetic acid (5-HIAA) in the urine.Epinephrine hydrochloride (2 to 10 μg.) was diluted . . .
Contribution of SPECT/CT 111In-DTPA Cisternography in the Localization of an Intermittent Cerebrospinal Fluid Leak in a 3-Year-Old Girl With Congenital Bone Defect
Authors: Geraldine Pina, Alexandru Szathmari, Christian Scheiber, Carmine Mottolese
Journal: Clinical Nuclear Medicine (2011)

We report the case of a 3-year-old girl with intermittent rhinorrhea discovered after resolution of pneumococcal meningitis. Cerebral MRI and thin section CT were not conducive in this particular case. The 111In-DTPA planar cisternography confirmed but could not localize the cerebrospinal fluid leak. An anterior plasty was unsuccessful. A second 111In-DTPA SPECT/CT cisternography was performed. Planar images were conclusive of cerebrospinal fluid leakage in the left medial skull base. Fused SPECT/CT images located the leakage in the left infratemporal fossae. A median skull base plasty was successfully performed.
AB0428 Study on the Efficacy and Safety of Tocilizumab in Patients with Rheumatoid Arthritis in Slovakia: One Year Results of Prospective, Open Label Study Close to Clinical Practice
Authors: I. Rybar, Z. Killinger, Z. Macejova, Z. Kmecova, E. Zanova, J. Rovensky
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To analyze the Slovakian experiences in a national multicenter open label non-interventional phase IV study which evaluated tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) and an inadequate response to conventional disease-modifying antirheumatic drugs (DMARDs) or tumor necrosis factor inhibitors (TNFs). <h3>Methods</h3> A prospective open label, single arm study with descriptive statistics used to analyze primary endpoint DAS28 and secondary endpoints: physical disability (HAQ) and safety. Adult patients with moderate to severe active RA who are on infusions therapy of TCZ (8mg/kg) every 4 weeks, after inadequate clinical response to a stable dose of DMARDs. Study has been approved by local ethical committees and all patients provided informed consent before enrollment. TCZ can be given with methotrexate (MTX), or as monotherapy in case of intolerance to MTX or when treatment with MTX was inappropriate. <h3>Results</h3> In 62 RA patients reached one year retention rate 89%. 7 patients were prematurely withdrawn: one of them because of ineffectiveness, 4 adverse events and 2 other reason (withdrawal of inform consent or loss of control). After one year 63% of enrolled patients were in remission (DAS28&lt;2,6) and other 19% reached low activity of disease (DAS28≤3,2). DAS28 index value decreased from baseline rate 6.54±0.78 to 2.99±1.26 (12 week), 2.82±1.21 (24 week), 2.29±1.04 (36 week) and 2.26±1.12 (48 week). After 12 months of TCZ treatment HAQ disability index decreased from average value 1,63±0,61 to 1,21±0,71, while improvment of the minimal clinically important difference (≥0,22) was recorded in 63% of patients. There were no new safety signals compared with other clinical studies. Adverse events have been confirmed in 28 patients, in 25 with low and moderate intensity. Serious adverse events occurred in 3 patients (1 arterial thrombosis, 1 acute sciatica with lumbar stenosis, 1 labile blood pressure). No case of death has been reported. <h3>Conclusions</h3> TCZ in Slovakian RA patients in open label study demonstrated high degree of one year retention rate (89%) with remission in 63% and low activity of disease in other 19% patient, without new safety signals. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1516
Factors associated with perforation related to diagnostic balloon-assisted enteroscopy: analysis of a national inpatient database in Japan
Authors: Hiroyuki Odagiri, Hiroki Matsui, Kiyohide Fushimi, Mitsuru Kaise, Hideo Yasunaga
Journal: Endoscopy (2014)

<b>Background and study aims: </b>Balloon-assisted enteroscopy (BAE) is a well-established procedure that is used worldwide for investigation of the small intestine. Previous reports describing the factors associated with perforation related to diagnostic BAE were limited by inclusion of only small numbers of patients who were mostly treated at a few specialized centers. The aim of this study was to clarify the factors associated with perforation by analysis of a large multicenter database. <b>Patients and methods:</b> This study retrospectively analyzed data from the Diagnosis Procedure Combination database in Japan. Patients who underwent diagnostic BAE between July 2007 and March 2013 were included. The primary outcome was the occurrence of perforation requiring open surgery. Logistic regression analysis was used to identify factors associated with perforation. <b>Results:</b> A total of 29 068 patients who underwent diagnostic BAE during the study period were identified. Perforation occurred in 32 patients (0.11 %). Univariable logistic regression analysis showed that patients with inflammatory bowel disease (IBD) on steroids had a significantly higher risk of perforation (odds ratio 8.55; 95 % confidence interval 2.87 – 25.5; <i>P</i> < 0.001). Non-IBD patients on steroids had an approximately three-fold higher risk of perforation compared with patients who were free from IBD and not taking steroids. <b>Conclusion:</b> Our results suggest that patients with IBD who are using steroids have the highest risk of perforation related to diagnostic BAE.
Sexually Transmitted Infections: Guidelines for Prevention and Treatment, by Michael Adler, Susan Foster, John Richens, Hazel Slavin
Authors: C. F Gilks
Journal: BMJ (1997)

Michael Adler, Susan Foster, John Richens, Hazel Slavin Overseas Development Administration, £6.95, pp 136 ISBN 0 902 500 902

Sexually transmitted infections are highly prevalent in poor countries and are a major cause of loss of healthy life years in women of childbearing age. Recently, they have assumed even greater importance because they are the main reducible risk factor for transmission of HIV. Previously largely ignored, they have become high priority targets for prevention and control. Unfortunately few policy makers and planners, or aid and donor organisations, have a wide general background in this complex subject—a problem which has important consequences for the advocacy and implementation of effective …
Abstract 4647: Caspase-dependent post-translational modulation of Mcl-1 by ABT-737 in acute lymphoblastic cell lines
Authors: Yong-Ku Ryu, Min H. Kang
Journal: Cancer Research (2012)

Abstract Background: ABT-737 is a BH3-mimetic that has a wide spectrum of single-agent activity against acute lymphoblastic leukemia (ALL) cell lines and xenografts. Previously (J Nat Cancer Inst 100:580-595, 2008), we reported that Mcl-1, an anti-apoptotic Bcl-2 family protein that is not inhibited by ABT-737, decreased in response to ABT-737 in ABT-737-sensitive ALL cell lines while a reactionary Mcl-1 increase is observed in ABT-737-resistant cell lines. In the current study, we investigated the pathways of Mc-1 down-regulation in response to ABT-737 in ALL cell lines. Methods: To identify caspase cleavage sites and to determine whether the cleavage products are pro-apoptotic or anti-apoptotic, we transduced into the NALM-6 ALL cell line lentiviral vectors with several Mcl-1 variants tagged with V5 epitope, including wild type: Mcl-1 1-350 full length tagged with V5, point mutations at aspartate 127 and aspartate 157 to alanine: Mcl-1 D127A and Mcl-1 D157A, and C-terminus fragments of caspase cleavage, deleted: Mcl-1 β127 and Mcl-1 α157. Localization of Mcl-1 1-350 and Mcl-1 β157 in ALL cells, cytosol and mitochondria were fractionated from the cells expressing the proteins, and Mcl-1 and V5 were assayed in the fractions. Results: The decrease in Mcl-1 by ABT-737 in ABT-737-sensitive cell lines was via formation of an Mcl-1 fragment which is prevented by a caspase inhibitor (Boc-d-fmk), but not a proteosome inhibitor (MG-132), indicating that Mcl-1 cleavage is caspase-dependent. Of the two caspase-dependent Mcl-1 cleavage sites (D127 and D157), D157 is the major site of cleavage in response to ABT-737 treatment in ALL cells. Localization experiments revealed that full length Mcl-1 resides in both the cytosol and mitochondrial fractions, while the Mcl-1_158-350 fragment localizes mostly to mitochondria. Caspase 3- and caspase 9-activation in response to ABT-737 was higher in transduced cells expressing the Mcl-1 β157 fragment, suggesting that the fragment increases sensitivity to apoptotic stimuli. Pretreating cells with okadaic acid, a protein phosphatase inhibitor, resulted in greater fragmentation of Mcl-1 in resistant cell lines while the effect of okadaric acid was minimal in a ABT-737-sensitive cell line, suggesting that dephosphorylation makes Mcl-1 more susceptible to Mcl-1 cleavage in response to ABT-737. Conclusion: Mcl-1 is cleaved to Mcl-1 β157 by caspases in ALL cells that are treated with ABT-737, and the pro-apopoptotic activity of Mcl-1 β157 contributes to a vicious cycle promoting cell death. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4647. doi:1538-7445.AM2012-4647
Inflammatory myofibroblastic tumor of the terminal ileum
Authors: T. Huang, P. Chen, Y. Liu, J. Jin
Journal: Endoscopy (2011)

A 37-year-old male was admitted to our hospital due to weight loss and passage of tarry stools. Upper gastrointestinal panendoscopy showed only gastritis. Abdominal computed tomography revealed one mass-like lesion with wall thickening of the ileum ([Fig. 1 a]).
Abstract 560: Development of an organotypic raft culture system to study the role of latent membrane protein 1 during Epstein-Barr virus replication
Authors: Vicki M. Geiser, Julie Girard, Mathias Godsil, Thomas Kahler, Emily Rausch, Hayley Rutledge
Journal: Cancer Research (2012)

Abstract Epstein-Barr Virus (EBV) is a gamma herpesvirus that is prevalent worldwide and is an important cause of acute and chronic disease. Primary EBV infection which occurs after early childhood often results in acute infectious mononucleosis. Persistent latent EBV infection is a causative agent of anaplastic nasopharyngeal carcinoma, AIDS related lymphoma, posttransplant lymphoma, and Hodgkin's disease. Expression of Latent Membrane Protein 1 (LMP1) is common to most EBV related malignancies. LMP1 induced NF-κB activity is required for efficient transformation and survival of primary human B lymphocytes into lymphoblastoid cell lines. Increasing evidence suggest that LMP1 has an important role in the lytic cycle. Studies indicate that LMP1 and other latent genes are induced as part of the EBV lytic cascade in Burkitt's lymphomas. Our recent research indicates that LMP1-deleted virus replicates as efficiently as wildtype virus in HEK293 cells which suggests that the role of LMP1 during lytic replication is linked to changes in the cellular environment. LMP1 expression is associated with survival signals and alters expression of several differentiation markers, therefore a role for LMP1 during lytic replication in differentiating epithelial cells should be pursued. We have developed an organotypic raft culture system that will permit investigation of EBV replication in differentiating epithelial cells. Our lab is utilizing molecular, biochemical, and genetic approaches to elucidate the role of LMP1 during EBV replication in differentiating epithelial cells. We are investigating the function of LMP1 in viral replication, cell proliferation and differentiation, and viral-cellular signaling pathways. Based on these studies we will develop a model for the role of LMP1 during EBV replication in differentiating epithelial cells and its resulting pathogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 560. doi:1538-7445.AM2012-560
WHOLE EXOME SEQUENCING IN CONGENITAL HEART DISEASE REVEALS VARIANTS IN LEFT-RIGHT PATTERNING GENES PREVIOUSLY ASSOCIATED WITH HETEROTAXY SYNDROME AND PRIMARY CILIARY DYSKINESIA
Authors: Keila N. Lopez, Alexander H. Li, Neil Hanchard, Mahshid Azamian, Seema Lalani, Heather Dickerson, Jim Lupski, Daniel Penny, Charles Fraser, James Martin, Eric Boerwinkle, John W. Belmont
Journal: Journal of the American College of Cardiology (2015)
Decreased Jejunal Uptake of Labeled Folic Acid (<sup>3</sup>H-PGA) in Alcoholic Patients: Roles of Alcohol and Nutrition
Authors: Charles H. Halsted, Enrique A. Robles, Esteban Mezey
Journal: New England Journal of Medicine (1971)

Abstract The jejunal uptake of labeled folic acid (3H-PGA) was measured in chronic alcoholic patients without definite liver disease. The intestine was perfused through a triple lumen tube with a solution containing 3H-PGA in a concentration of 25 ng per milliliter. Uptake was low in eight patients who gave a history of poor diet during the alcoholic binge that preceded admission (20.4 per cent ± 4.16 S.D.). A significantly greater value was obtained in nine abstinent subjects fed a hospital diet for two weeks (36.5 per cent ± 5.75). The subsequent administration of ethanol for two weeks to seven patients did not change the mean uptake of 3H-PGA (34.8 per cent ± 9.87). This study confirms that the absorption of folic acid is decreased in malnourished, actively drinking alcoholics. The data suggest that the functional defect is caused by poor nutrition rather than a toxic effect of ethanol on the jejunum.
Pancreatic stent eroding into the stomach
Authors: S. Rana, H. Dhaliwal, V. Sharma, V. Chaudhary, D. Bhasin
Journal: Endoscopy (2013)

A 32-year-old alcoholic man diagnosed as having acute necrotizing pancreatitis and being managed conservatively developed high-grade fever not responsive to intravenous antibiotics. A percutaneous catheter inserted into the large, infected acute necrotic collection drained frank pus. The patient gradually improved and contrast-enhanced computed tomography (CECT) 3 weeks later revealed a marked reduction in the size of the collection. The transgastric route of the percutaneous catheter was visible on the CECT scan. The catheter continued to drain 300 – 500 mL of clear pancreatic juice and 4 weeks later the patient underwent endoscopic retrograde pancreatography (ERP). This revealed a complete pancreas divisum with partial disruption of the dorsal duct. A bridging 5-Fr stent was placed through the minor papilla and the patient showed marked improvement, with the external drainage of pancreatic juice subsiding after 2 weeks. The percutaneous catheter was thereafter removed. After another 4 weeks, the patient underwent another ERP for removal of the stent and to document healing of the ductal disruption. During the passage of the duodenoscope into the stomach a stentlike foreign body was seen in the stomach, protruding through the posterior wall ([Fig. 1]). The transpapillary stent placed a few weeks earlier was seen at the papilla but the flanges had migrated inwards ([Fig. 2]). Fluoroscopic examination revealed that the transpapillary stent had migrated into the stomach through the pancreatic duct disruption, following the route created by the transgastric percutaneous catheter ([Fig. 3]). The stent was removed via the minor papilla ([Fig. 4]) and a pancreatogram revealed persistence of ductal disruption. A bridging 5-Fr transpapillary stent was placed. ERP was repeated 4 weeks later and revealed healing of both the ductal disruption and the fistulous opening in the stomach.
Kidney Transplantation from Unrelated Living Donors
Authors: Andrew S. Levey, Susan Hou, Harry L. Bush
Journal: New England Journal of Medicine (1986)

Before dialysis therapy was routinely available in the United States, both related and unrelated living donors were accepted for renal transplantation. By 1965, data from the Registry in Human Kidney Transplantation indicated that the success of kidney transplantation from unrelated living donors and from cadaveric donors was similar.1 With the increasing availability of dialysis, most centers discouraged transplantation from poorly matched living donors on the premise that a cadaveric kidney provides an equal benefit to the recipient, without risk to a living donor. In the past 20 years, the results of transplantation have improved to such an extent that today . . .
Case 28-2014
Authors: Read Pukkila-Worley, Valentina Nardi, John A. Branda
Journal: New England Journal of Medicine (2014)

A 39-year-old man was admitted to the hospital, 10 days after receiving prednisone for severe contact dermatitis, because of headache, nausea, and photophobia. Examination of the cerebrospinal fluid revealed white cells and gram-positive cocci. Diagnostic tests were performed.
RESTENOSIS PATTERN OF SECOND-GENERATION DRUG-ELUTING STENT
Authors: Tahei Ichinohe, Kazushige Kadota, Takenobu Shimada, Hidewo Amano, Yu Izawa, Takenori Kanazawa, Shunsuke Kubo, Koshi Miyake, Noriyuki Ohashi, Yuki Hayakawa, Daiji Hasegawa, Suguru Otsuru, Seiji Habara, Hiroyuki Tanaka, Takeshi Tada, Yasushi Fuku, Harumi Katoh, Tsuyoshi Goto, Kazuaki Mitsudo
Journal: Journal of the American College of Cardiology (2015)