tbuckley/cabot-search huggingface dataset:
Abstract 558: Bortezomib induction of the unfolded protein response mediates Epstein-Barr virus lytic activation but is separable from bortezomib-induced cytotoxicity
Authors: Courtney Shirley, Nene Kalu, Meir Shamay, Richard F. Ambinder
Journal: Cancer Research (2012)

Abstract Epstein-Barr virus (EBV) is associated with many human cancers. Several therapeutic strategies involving the pharmacologic activation of the EBV lytic cycle for tumor killing have been described (1-2). We previously identified bortezomib, a proteasome inhibitor approved for the treatment of multiple myeloma and mantle cell lymphoma, as a potent activator of EBV lytic gene expression. The mechanism of action of bortezomib as either a viral lytic activator or an anticancer drug remains poorly understood. However, induction of the unfolded protein response (UPR) has emerged as a central theme in both areas of investigation (3). In order to further evaluate the role of the UPR in lytic activation, we treated lymphoid and epithelial tumor cell lines with bortezomib and assessed induction of the UPR and EBV lytic gene expression. We found dose-dependent parallel induction of UPR and EBV lytic infection across cell lines. However, an EBV-immortalized lymphoblastoid cell line was relatively resistant to both bortezomib-induced UPR and induction of EBV lytic gene expression, but not resistant to bortezomib-induced cell killing. To further investigate, we assessed induction of the UPR by thapsigargin which leads to depletion of Ca2+ in the ER. Thapsigargin induced the UPR and EBV lytic gene expression across all the cell lines tested. Blocking ER stress and UPR activation, by cycloheximide treatment or by BiP knockdown, diminished EBV lytic gene expression but had no effect on cellular toxicity. Additionally, regulated knockdown of UPR associated transcription factors (XBP1(s), c-Jun) blocked lytic activation by both agents. Taken together, these results suggest that induction of the UPR by bortezomib is tightly linked to EBV lytic activation but may be separable from the cytotoxic effects of bortezomib. References: 1. Fu DX, Tanhehco Y, Chen J, Foss CA, Fox JJ, Chong JM, Hobbs RF, Fukayama M, Sgouros G, Kowalski J, Pomper MG, Ambinder RF. Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors. Nat Med. 2008; 14(10):1118-22. 2. Feng WH, Hong G, Delecluse HJ, Kenney SC. Lytic induction therapy for Epstein-Barr virus-positive B-cell lymphomas. J Virol. 2004; 78(4):1893-902. 3. Shirley CM, Chen J, Shamay M, Li H, Zahnow CA, Hayward SD, Ambinder RF. Bortezomib induction of C/EBPα mediates Epstein-Barr virus lytic activation in Burkitt lymphoma. Blood. 2011; 117(23):6297-303. 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 558. doi:1538-7445.AM2012-558
Gastric inflammatory myofibroblastic tumor masquerading as a pancreatic cystic neoplasm
Authors: A. Fong, A. Teoh, P. Chiu, S. Wong, E. Ng
Journal: Endoscopy (2010)

A 56-year-old man presented with epigastric pain since 2 weeks. Esophagogastroduodenoscopy (EGD) revealed a 3-cm submucosal mass in the posterior wall of the gastric body. Abdominal ultrasound showed a multilocular cystic lesion (10 × 6 × 9 cm) in the pancreatic tail. Endoscopic ultrasound (EUS) confirmed a multicystic lesion arising from the pancreas ([Fig. 1]).
CENTRAL INDICES OF AORTIC STIFFNESS PREDICT SEVERITY AND BURDEN OF CORONARY ARTERY DISEASE BEYOND TRADITIONAL RISK MODELS
Authors: Tilak Pasala, Shervin Golbari, Sonika Golbari, Prasanna Sengodan, Florian Rader, Theophilus Owan, Anwar Tandar, Mark Dunlap, Sanjay Gandhi
Journal: Journal of the American College of Cardiology (2016)
Abstract P5-03-14: Expression of ALDH1 in metastasizing axillary lymphnodes in breast cancer
Authors: A Shi, Y Dong, L Bi, N Xu, Z Fan, S Li, H Yang, Y Li
Journal: Cancer Research (2012)

Abstract Background: There is increasing evidences that a wide variety of malignancies, including breast cancer, may be driven by a small subset of ‘tumor-initiating cells’ or ‘cancer stem cells’ (CSC) which are able to form tumors in immunocompromised mice as well as to generate the phenotypic heterogeneity of the initial tumor. Enzyme aldehyde dehydrogenase (ALDH1) has been reported as a possible marker for mammary CSC. These cells are a source of tumor recurrence and metastasis, and are resistant to chemotherapy, radiotherapy and hormone therapy. Objective: Assuming that the detection of CSC in axillary lymph nodes is more effective to predicting cancer outcome than the widely used detection of cancer cells in axillary lymph nodes, we measure ALDH1 levels to predict their presence into axillary lymph nodes on development of cancer and anticipate outcomes. Methods: ALDH1 protein was detected by an immunohistochemical technique in 229 cases of breast cancer diagnosed from 2002 to 2011 Follow-up ranged from 11.5 months to 96.9 months, with a mean of 73.9 months. A survival assay was used to determine the relationship between distant metastatic rate and survival rate. Results: ALDHl expression was detected in 79cases and the Positive rate in metastatic axillary lymph nodes was 34.5%. Negative ER, PR status were related to the ALDH1 positive cases(P = 0.012). See Table 1. Mortality rate between ALDH1 positive cases (50.8%) and negative cases (28.8%) were significantly different (P = 0.001). See Table 2. Further, survival analysis of recurrence-free survivals (RFS) and survival rate decreased significantly between ALDHl positive and negative cases (P = 0.001) (see table 2) and COX analysis shows that ALDH1 expression is an independent predictor of poor outcome in breast cancer(P = 0.011). Discussion: What cancer stem cells migrate to the axillary nodes have more important prediction than that the matastesis of normal cancar cells in axillary node. It might be a role resulting in dying in breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-03-14.
Associated Focal and Segmental Glomerulosclerosis in the Acquired Immunodeficiency Syndrome
Authors: T. K. Sreepada Rao, Edward J. Filippone, Anthony D. Nicastri, Sheldon H. Landesman, Elliot Frank, C. K. Chen, Eli A. Friedman
Journal: New England Journal of Medicine (1984)

Of the 92 patients with the acquired immunodeficiency syndrome (AIDS) who were seen at our institution over a two-year period, 9 acquired the nephrotic syndrome (urinary protein >3.5 g per 24 hours) and 2 had azotemia with lesser amounts of urinary protein. Five of these 11 patients had a history of intravenous-heroin addiction, but in the remaining six, there were no known predisposing factors for nephropathy. In nine patients (including the six non-addicts) the course of renal disease was marked by rapid progression to severe uremia. Renal tissue examined by biopsy in seven patients and at autopsy in three revealed focal and segmental glomerulosclerosis with intraglomerular deposition of IgM and C3. In the 11th patient, renal biopsy revealed an increase in mesangial matrix and cells, with deposition of IgG and C3 consistent with a mild immune-complex glomerulonephritis, and severe interstitial nephritis. We conclude that focal and segmental glomerulosclerosis may be associated with AIDS and suggest that rapid deterioration to uremia may characterize this renal disease. (N Engl J Med 1984; 310:669–73.)
Abstract 754: Heat shock protein vaccines for immunotherapy ofHer-2/neu positive breast cancers
Authors: Annalise Smith, Darlah M. Lopez Rodriguez, Eckhard R. Podack, Samita S. Andreansky
Journal: Cancer Research (2011)

Abstract Over-expression of Her-2/neu protein, a member of the epidermal growth factor receptor (EGFR) involved in cell growth results in cancer development. 20-30% of breast cancers over-express Her-2/neu protein and this has been correlated with poor prognosis, leading to recurrence after their initial treatment. Thus new strategies are necessary to combat this devastating disease. The selective expression of HER-2/neu in epithelial carcinogenesis makes HER-2/neu antigen an ideal target for immunotherapy. The objective of our research is to explore vaccine strategies that impacts both B and T cell responses in HER-2/neu breast cancer models. We are exploring heat shock proteins (HSP) vaccines that will chaperone tumor-associated antigens including our antigen of interest Her-2/neu protein to elicit innate and adaptive responses. We are utilizing the rat Her-2/neu as our model antigen and are administering these vaccines in transplantable and transgenic her-2/neu murine models after tumor implantation. Our first approach was to generate a Her-2/neu derived HSP gp96 in a secretable form. It has been reported that gp96 can ubiquitously bind to cell associated peptides and cross present these antigens to CD8+ T-cells to generate an effective cytotoxic T cell (CTL) response. Cancer cells expressing rat Her-2/neu were stably transfected with a mouse gp96IgG eukaryotic expression vector, where the endoplasmic retention signal sequence KDEL of gp96 was replaced with the hinge and CH2 and CH3 domains of murine IgG1. 2×104 stably transfected cells secreted within 24h 100- 200ng gp96IgG. Our goal is to generate Her-2/neu specific CD8 T cell responses that would result in vivo tumor delay. Our second approach was to test the adjuvanticity of a mixture of HSPs in combination with irradiated tumor cells. Administration of the vaccine in a therapeutic setting not only delayed tumor growth, but also provided survival benefit. Additionally, vaccinated animals were superior in eliciting Her-2/neu specific antibody response when compared to the HSP vaccine or the irradiated tumor cells alone. Our long-term goal is to combine both approaches to enhance cytotoxic T cell (CTL) and B cell specific response against Her-2/neu specific cancers. Funded by: American Cancer Society MRSG# 08-064-01-LIB and Women's Cancer Association 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 754. doi:10.1158/1538-7445.AM2011-754
Use of a Hyperbaric Solution for Administration of Intrathecal Amphotericin B
Authors: Naomi P. Alazraki, Joshua Fierer, Samuel E. Halpern, Richard W. Becker
Journal: New England Journal of Medicine (1974)

Repeated intrathecal administration of amphotericin B is often used in treatment of patients with fungal meningitis, but cisternal injections are hazardous and lumbar injection may cause local arachnoiditis. To study the distribution of hyperbaric solutions of amphotericin in 10 per cent dextrose in water, such solutions mixed with 131I albumin were injected into the lumbar space of 21 monkeys, and external radioactivity was monitored to estimate the amount of injected material that reached the cisterna magna. Higher cisternal concentrations of radioisotope were found in the 12 monkeys that were injected with hyperbaric material and then placed in the Trendelenburg position than in nine monkeys that were supine and given non-hyperbaric amphotericin solutions. This technic may prove useful in treatment of fungal meningitis. (N Engl J Med 290:641–646, 1974)
Wilson, Strokes, and Zebras
Authors: Michael F. Marmor
Journal: New England Journal of Medicine (1982)

WOODROW Wilson is ranked among the great presidents of the United States, but he is an enigmatic figure to historians and political scientists because his career repeated a pattern of brilliant success followed by acrimonious battle with rivals and ultimate defeat. As president of Princeton University (1902–1910) he was an effective leader at first, accomplishing much-needed reforms to strengthen the undergraduate educational system. But in 1907 he became embroiled in controversy with another powerful Princeton figure, Dean Andrew F. West, over the site for the construction of a proposed graduate college, and he became so intransigent that he alienated a . . .
Evaluation of Anaplastic Lymphoma Kinase (ALK) Inhibitor Brigatinib [AP26113] in Patients (PTS) with Alk+ Non–Small Cell Lung Cancer (NSCLC) and Brain Metastases
Authors: D. Kerstein, S. Gettinger, K. Gold, C.J. Langer, A.T. Shaw, L.A. Bazhenova, R. Salgia, D.J. Dorer, M.G. Conlan, D.R. Camidge
Journal: Annals of Oncology (2015)
FRI0354 Efficacy of infliximab in the treatment of sight-threatening uveitis in behçet’s disease
Authors: F. Ajili, S. Bellakhal, L. Metoui, S. Sayhi, N. Boussetta, J. Laabidi, B. Louzir, N. Ben Abdelhafidh, S. Othmani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Despite intensive immunosuppressive therapy, permanent loss of vision resulting from relapsing ocular inflammation occurs frequently in Behçet’s disease. Since tumor necrosis factor (TNF) have a pathogenic role in Behçet’s uveitis, the use of infliximab (a monoclonal antibody against TNF-α) have been suggested in resistant Behçet’s uveitis <h3>Objectives</h3> We aim to evaluate the responsiveness of patients with severe uveitis associated with Behçet’s disease to infliximab. <h3>Methods</h3> We retrospectively reviewed the medical charts of Behçet’s disease patients with severe uveitis treated with infliximab infusions. <h3>Results</h3> Among 33 patients followed for Behçet’s uveitis in our internal medicine department, seven patients were treated with infliximab infusions. The mean age of these patients was 33.7 years (range 24-44 years), they were all men. Six patients had bilateral panuveitis and one patient had bilateral posterior uveitis. Retinal vasculitis was associated to uveitis in all patients. Three patients had neurological involvement in addition to ocular lesions, another patient had vascular involvement. The infliximab was given at a dose of 3mg/kg in weeks 0, 2, 6 than every 8 weeks. The number of infliximab infusions ranges from 5 to 22 infusions. Before receiving infliximab patients were treated with conventional immunosuppressive agents which includes cyclophosphamide, azathioprine and cyclosporine. Before the Infliximab infusions onset, 71% of patients had a visual acuity under than 1/10. One year after the infliximab onset this frequency decreased to 29%. The number of ocular relapses decreased after the infliximab onset and ranges from 0 to 4 flares. One patient had no more relapse after one year of infliximab treatment. <h3>Conclusions</h3> The use of infliximab in the therapeutic regimen of Behçet’s uveitis had improved the visual prognosis of the ocular involvement of Behçet’s disease. The cost of infliximab could limit the use of this treatment in the management of Behçet’s uveitis. <b>Disclosure of Interest</b>: None Declared
Left Ventricular Function in Chronic Obstructive Lung Disease
Authors: George L. Baum, Arthur Schwartz, Roberto Llamas, Cesar Castillo
Journal: New England Journal of Medicine (1971)

Abstract In 15 patients with chronic obstructive lung disease, biventricular cardiac catheterization showed that left ventricular end-diastolic pressure was elevated in seven, and abnormal left ventricular function curves were found in 14. Analysis of left ventriculography revealed increased wall thickness or diastolic chamber size (or both) in nine of 10 observations and impaired ventricular performance in three of eight. The degree of functional impairment was not influenced by the presence or absence of right-sided heart failure. Appreciable coronary narrowing was found in only two of 10 subjects studied by cineangiography. Left ventricular dysfunction was present in most of the patients studied. The pathogenesis of the dysfunction is not clear.
Adjuvant Regorafenib in Stage IV Colorectal Cancer (CRC) After Curative Treatment of Liver Metastases: A Phase III Randomized, Placebo-Controlled Study (COAST)
Authors: Van Cutsem Eric, Yoshino Takayuki, Xu Rui-Hua, Zalcberg John, Sargent Daniel, Choti Michael, Rutstein Mark, Cupit Lisa, Kuss Iris, Grothey Axel
Journal: Annals of Oncology (2014)
OP0208 Diagnostic Value of the Number of Affected Branches of the Temporal Artery by Color Doppler Ultrasonography in Giant Cell Arteritis
Authors: W. A. Sifuentes Giraldo, A. L. Boteanu, A. Rodriguez Garcia
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> During the last decade of color Doppler ultrasonography (CDUS) has emerged as a noninvasive diagnostic modality in patients with suspected giant cell arteritis (GCA). Numerous studies suggest that the presence of the 'halo sign' [HS], which probably translates arterial wall edema, is highly specific for GCA, especially if it is bilateral. However, there are no studies correlating the number of branches affected with definitive diagnosis by biopsy. <h3>Objectives</h3> To determine if the number of branches of the temporal artery with HS influences CDUS diagnostic performance parameters for ACG. <h3>Methods</h3> We conducted a prospective observational study in all consecutive patients with suspected GCA treated in our department during the period 2007-2012, which underwent USDC and biopsy temporal arteries. We evaluated sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) of HS in temporal artery compared with histologic confirmation of arteritis (gold standard), in both global and according the number of branches involved. <h3>Results</h3> The study included 52 patients, 36 were women (69%), with a mean age 77.3 ± 6.7 years (range 58-93). All patients met 3 or more classification criteria of the American College of Rheumatology for GCA, being the most common clinical manifestation recent-onset headache (85%) and presenting eritrosedimentation ratio ≥50 mm/h in 86.5% cases. The biopsy was positive in 22 cases (42%). CDUS detected HS in 28 cases (54%), with involvement of one branch in 13%, 2 branches in 33%, and 4 branches in 54%. The global values obtained for presence of HS were SE 91%, SP 73%, PPV 71% and NPV 73%. The values obtained analyzing each number of involved branches are shown in Table. There was statistical significance only when 2 or more branches were affected and the best diagnostic performance ocurred when 4 branches were affected. <h3>Conclusions</h3> Conclusions: Our results demonstrate that the diagnostic performance of the DCUS can be improved taking into account the number of branches with HS. This would accelerate the onset of treatment without performing a biopsy in patients with typical symptoms and several branches affected, reserving it for patients with atypical or have only one or no branch with HS. <h3>Disclosure of Interest</h3> None Declared
Predictive prognostic value of local and distant recurrence of F-fluorodeoxyglucose positron emission tomography for pancreatic neuroendocrine tumors with reference to World Health Organization classifications (2004, 2010). Case series study
Authors: H.J. Durán, B. Ielpo, E. Díaz, I. Fabra, R. Caruso, L. Malavé, O. Cano-Valderrama, L. Garcia, Y. Quijano, E. Vicente
Journal: International Journal of Surgery (2016)
AB0543 Remission using different composite disease indices in MTX-IR RA patients treated with abatacept or infliximab, +MTX:
Authors: J. Smolen, M. Dougados, C. Gaillez, C. Poncet, M. Le Bars, A. Elegbe, M. Schiff
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Levels of acute-phase reactants, which correlate with clinical disease activity in RA,<sup>1</sup> are differentially weighted in the calculation of disease activity indices such as DAS28/SDAI. Acute-phase reactants and disease activity measures may be affected differently by biologics with different mechanisms of action.<sup>2</sup> <h3>Objectives</h3> To evaluate remission using the ACR/EULAR index-based definition of remission<sup>3</sup> vs DAS28-defined remission in biologic-naïve MTX-IR RA patients (pts) from AIM<sup>4</sup> and ATTEST<sup>5</sup> trials, and assess the contribution of core components. <h3>Methods</h3> In AIM, pts were randomized to abatacept (ABA; ∼10 mg/kg every 4 wks) or PBO, plus MTX.<sup>4</sup> In ATTEST, pts were randomized to ABA (∼10 mg/kg every 4 wks), IFX (3 mg/kg every 8 wks), or PBO (every 4 wks), plus MTX.<sup>5</sup> Post-hoc analyses evaluated remission according to DAS28(CRP) and SDAI at 6 mths; missing data were imputed by LOCF. <h3>Results</h3> Baseline demographics and disease characteristics were similar between groups in each trial.<sup>4,5</sup> All pts achieving DAS28 remission at 6 mths were either in SDAI remission or SDAI LDAS. At 6 mths, for pts achieving SDAI remission, core components were generally similar and≤1. <h3>Conclusions</h3> In ATTEST, remission rates at 6 mths were similar for abatacept and IFX independent of the composite measure. When using SDAI remission criteria to assess remission, core components of abatacept-treated pts were consistent in AIM and ATTEST and similar to that of IFX-treated pts and ≤1, suggesting no residual disease activity in contrast with DAS28 remission criteria. This confirms that SDAI is a more accurate composite index than DAS28-CRP in assessing true remission. <h3>References</h3> Mallya RK et al. J Rheumatol 1982;9:224–8; Smolen JS, Aletaha D. Arthritis Rheum 2011;63:43–52; Felson DT et al. Ann Rheum Dis 2011;70:404–13. Kremer JM et al. Ann Int Med 2006;144:865–76; Schiff M et al. Ann Rheum Dis 2008;67:1096–103. <h3>Disclosure of Interest</h3> J. Smolen Grant/Research support from: Abbott Laboratories, Bristol-Myers Squibb, Hoffmann-La Roche, Inc., Schering-Plough, UCB, Inc., Pfizer, Consultant for: Abbott Laboratories, Amgen Inc., AstraZeneca, Bristol-Myers Squibb, Centocor, Inc., Eli Lilly and Company, Merck, Novo Nordisk, Roche, sanofi-aventis, UCB, Inc., M. Dougados Grant/Research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Speakers Bureau: Bristol-Myers Squibb, C. Gaillez Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, C. Poncet: None Declared, M. Le Bars Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, A. Elegbe Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Schiff Consultant for: Bristol-Myers Squibb
Ultraslim endoscope-assisted therapeutic ERCP for inaccessible papilla by a double-balloon enteroscope in patients with Roux-en-Y anastomosis
Authors: T. Itoi, K. Ishii, A. Sofuni, F. Itokawa, T. Kurihara, T. Tsuchiya, S. Tsuji, N. Ikeuchi, F. Moriyasu
Journal: Endoscopy (2011)

Roux-en-Y anastomosis has been thought to preclude endoscopic access for endoscopic retrograde cholangiopancreatography (ERCP) [1]. The balloon enteroscopy can be useful for performing ERCP in patients with Roux-en-Y anastomosis [2] [3] [4] [5]. However, even if the enteroscope reaches a terminal portion of the afferent limb, the major papilla cannot always be detected. Here, we describe a case of successful ERCP using an ultraslim endoscope for inaccessible papillae by double-balloon enteroscopy (DBE) in a patient with Roux-en-Y anastomosis.