tbuckley/cabot-search huggingface dataset:
Abstract P6-08-06: C-Reactive Protein Expression and Its Association with Disease Specific Survival and Disease Recurrence in ER Negative Breast Cancer Patients
Authors: B Elsberger, C Tannahill, C Orange, EA Mallon, C Wilson, JC Doughty, J. Edwards
Journal: Cancer Research (2010)

Abstract Background: The systemic inflammatory response, as evidenced by elevated serum C-reactive protein (CRP) has been reported to be predictive of poor survival, independent of tumour stage, in a variety of solid tumours (1). Previous studies suggest that systemic elevated serum CRP did not predict relapse-free, cancer-specific (DSS) nor overall survival (2). Aim of this study was to examine the relationship between expression of CRP within ER negative breast cancers and patients’ clinical outcome. Methods: Tissue microarray technology was employed to analyse tissue taken from 171 ER negative breast cancer patients at time of surgery. Immunohistochemistry was performed using an antibody to CRP. Expression was assessed using the weighted histoscore method by two independent scorers. Results: Cohort's median age was 56 years and tumour size was 20mm, 22% were pathologically graded G2 and 74% G3 and 46% were lymph node positive. 60% underwent a mastectomy, 56% received radiotherapy and 67% chemotherapy. 33% had recurrence after a median time of 5.6 years. 47/171 patient were deceased at time of analysis. There was a definitive trend noticed between high nuclear and cytoplasmic CRP expression and DSS (p=0.078 and p=0.173, figure 1a and 1b) and recurrence (p=0.133, p=0.253, figure 2a and 2b). There was a significant association seen with high CRP expression in the surrounding tumoural stroma and DSS (p=0.007) as well as recurrence (p=0.016). Conclusion: Due to small patient numbers only trends indicating that high CRP expression within and surrounding the tumour play an important role in ER negative patients regards poorer survival and earlier recurrence. We are currently expanding our cohort further. References: (1) Roxburgh CSD (2009). Future Oncol. 2010 Jan;6(1):149-63 (2) Al Murri AM (2007) British Journal of Cancer, 96, 891-895 Figure available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-08-06.
A Call to WAR
Authors: M E Randall
Journal: JNCI Journal of the National Cancer Institute (1993)

In 1986, the Gynecologic Oncology Group (GOG), in view of reasonable data supporting a curative role for radiation therapy in ovarian carcinoma (7), activated a randomized protocol to determine the relative merits of whole abdominal radiation (WAR) versus platinum-based chemotherapy.This protocol embodied what was considered to be the crucial question, namely, which therapy given adjuvantly produced better survival and progression-free interval-chemotherapy or whole abdominal radiation?This question, however, was not answered, because patient accrual for the study was inadequate.After many trials of chemotherapy alone, little if any progress has been made, except to determine which treatments don't work well.
FRI0173 Gastrointestinal perforations with certolizumab PEGOL
Authors: R. Fleischmann, A. Rubbert-Roth, B. Combe, B. VanLunen, P. Andrews, M. de Longueville
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Gastrointestinal (GI) perforations have emerged as an uncommon but potentially serious safety concern for patients with rheumatoid arthritis (RA).<sup>1</sup> It is thought that treatment with some biologics (particularly those targeting the IL-6 pathway) may increase the risk of GI perforation in RA patients.<sup>2</sup> Certolizumab Pegol (CZP) is an anti-TNF registered in RA. <h3>Objectives</h3> To assess the rate of GI perforations occurring in CZP-treated RA patients for a total of &gt;8500 patient years (PY). <h3>Methods</h3> A pooled safety analysis was performed for 7 randomized controlled trials (RCTs) of CZP in RA and their open-label extensions (OLEs). RCTs included RAPID 1, RAPID 2, FAST4WARD and REALISTIC. Pooling was performed across all CZP doses. GI perforations were defined according to the preferred terms "gastrointestinal perforation" and "diverticular perforation". Cases were recorded by the clinical investigator. <h3>Results</h3> As of 31st October 2010, 3397 RA patients had been treated with CZP in all studies (RCTs plus OLEs) for a total of 8658 PY. The pooled safety analysis revealed that 1 GI perforation (0.01 events/100 PY) and 1 diverticular perforation (0.01 events/100 PY) occurred in all studies. No cases occurred during the RCTs. The first case of GI perforation occurred in a 64 year old female treated with CZP 200 mg Q2W for 9 months, MTX, diclofenac and oral corticosteroids. The patient was hospitalized for a peritonitis related to colonic perforation, which was successfully treated by surgery. The second case, a diverticular perforation, occurred in a 61 year old male treated with CZP 400 mg Q4W for 2.6 years, MTX and oral corticosteroids. The patient was hospitalized for peritonitis due to perforated diverticulitis of the sigmoid colon and was successfully treated by sigmoid resection. <h3>Conclusions</h3> No safety signal exists for an increased risk of GI perforations associated with the use of CZP. <h3>References</h3> Curtis JR et al. Arthritis &amp; Rheumatism 2011;63:346-351. Schiff et al. Arthritis Research &amp; Therapy 2011;13:R141. <h3>Disclosure of Interest</h3> R. Fleischmann Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, A. Rubbert-Roth Consultant for: UCB Pharma, Speakers Bureau: UCB Pharma, B. Combe Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, B. VanLunen Employee of: UCB Pharma, P. Andrews Employee of: UCB Pharma, M. de Longueville Employee of: UCB Pharma
AB0133 Urinary neutrophil gelatinase-associated lipocalin and monocyte chemoattractant protein-1 in a murine model of systemic lupus erythematosus
Authors: S. Vagnani, C. Tani, L. Carli, F. Querci, R. Talarico, C. Baldini, A. Della Rossa, S. Bombardieri, M. Mosca
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Monocyte Chemoattractant Protein-1 (MCP-1) are promising biomarkers in lupus nephritis (LN). Recent data in human and mice systemic lupus erythematosus (SLE) highlight their potential involvement in LN pathogenesis; however controversial data exist on their role as marker of renal disease activity or damage. <h3>Objectives</h3> The present study is aimed at evaluating urinary levels of NGAL and MCP-1 in a murine SLE model. <h3>Methods</h3> Eight-weeks old female New Zealand Black/ White F1 mice (NZ) were used as SLE models and were compared to eight-weeks old C57BL6/J mice. In order to follow the disease course, body weight was periodically monitored and urinary protein excretion was weekly detected by dipstick analysis (Combur Test M; Roche). Weekly the urine samples were used to evaluate NGAL and MCP-1 levels by immunoassorbent assays (Mouse MCP-1 Elisa kit, Thermo Scientific; Mouse NGAL Elisa kit, Bioporto Diagnostics). At different disease stages (8, 18, 24, 30, 36, 40 weeks) the animals weresacrificed and peripheral blood serum samples were collected. Anti-dsDNA autoantibodies were analyzed by the enzyme immunoassorbent assay (ELISA) method using a commercial kit according to the manufacturer’s instructions (Mouse anti-dsDNA IgG ELISA Kit, Alpha Diagnostics International). <h3>Results</h3> In the NZB/NZW F1 mice the average weight was 14.4 g at 8 weeks of age and it increased until week 36. The mean increase from week 8 to week 36 was 7.4 g. The mean urinary excretion of proteins was 72±34 mg/dl at 8 weeks of age and it increased in the course of the disease: 293±340 mg/dl and 624±469 mg/dl at 18 and 24 weeks of age. From week 8 to week 36 NGAL and MCP-1 urinary levels were not statistically significant while an important peak was detected on day 40: 2.00±0.94 ng/mland 5954±3921pg/ml respectively. In the NZB/NZW F1 mice serum titers of IgG auto-antibodies with specificity for dsDNA were negative until the 18<sup>th</sup> week (100% of the samples negative) becoming positive from the 24<sup>th</sup> week of age (70% of the samples positive). During the disease course no clinical and serological changes were observed in C57BL/6J mice; in particular, anti-dsDNA autoantibodies titers were negative in all experimental groups and urinary MCP-1 and NGAL concentrations did not increase in the observing time. <h3>Conclusions</h3> The NZB/NZW F1 mice show abnormal clinical and serological parameters that tend to accrue over time during the disease course. While the appearance of anti-dsDNA autoantibodies is associated with increase in proteinuria, in our model urinary NGAL and MCP-1 seem to come after the first signs of the renal disease and they could represent late renal disease markers. <h3>Disclosure of Interest</h3> None Declared
Abstract 1736: Skewed usage of TCRVbeta repertoire and predictive role of CD60 and CD49d expression in the survival rate of patients with Sézàry Syndrome
Authors: Enrico Scala, Deborah Pomponi, Maria Grazia Narducci, Giuseppe Alfonso Lombardo, Elisabetta Caprini, Marina Liso, Adriano Mari, Giandomenico Russo
Journal: Cancer Research (2010)

Abstract Background: Sézary Syndrome (SS) is a rare and aggressive leukemic variant of Cutaneous T-Cell Lymphoma (CTCL) characterised by erythroderma and the presence of a malignant circulating memory CD4+ T cell clone with skin homing characteristics, lack of CD26 and CD49d and over-expression of CD60. The availability of a large panel of monoclonal antibodies to CDR3 Vß epitopes, allows the study of the TCR repertoire by flow cytometry and a more precise identification of the malignant clone phenotypic characteristics. Objective: The aim of this study was to evaluate both the distribution of TCR-Vß family and CD60/CD49d expression within the clonal T cell population in patients affected by SS. Methods: We studied, by five-color flow cytometry analysis, TCR-Vß repertoire in 62 patients affected by SS, in 180 patients with MF, 6 cases of B cell Lymphomas (BCL), 19 with chronic Eczema (CE) recruited and followed from 1998 to 2008. A sequential gating strategy was used in order to examine the CD60 and CR49d expression within the neoplastic clonal population identified through the TCR-Vß repertoire analysis. Results and Conclusion: A skewed usage of only 4 out of 25 TCR-Vß subfamilies was observed in circulating T cell clone in 61.9% of patients affected by SS. TCR-Vß 2 and 5.1 were the most frequently represented (42.8% of TCR-Vß reactive patients), followed by TCR-Vß 12 and 13.1. In 20 cases the TCR-Vß panel was unable to identify the neoplastic clone, recognizing less than 5% of T cells, thus representing an indirect proof for the presence of a clonal population. CD60 was over expressed and CD49d down regulated within clonal T lymphocytes. This phenotype of the dominant T cell clone in the peripheral blood of patients with SS was significantly associated with a lower survival rate (chi-square 5.467, p &amp;lt;0.019). Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 1736.
AORTIC ANGULATION ATTENUATES PROCEDURAL SUCCESS FOLLOWING SELF-EXPANDABLE BUT NOT BALLOON-EXPANDABLE TRANSCATHETER AORTIC VALVE IMPLANTATION
Authors: Yigal Abramowitz, Yoshio Maeno, Tarun Chakravarty, Geeteshwar Mangat, Yoshio Kazuno, Nobuyuki Takahashi, Hiroyuki Kawamori, Mamoo Nakamura, Wen Cheng, Hasan Jilaihawi, Raj Makkar
Journal: Journal of the American College of Cardiology (2016)
Ga-67 Uptake in the Aorta in Wegener's Granulomatosis: Overlap with Takayasu's Arteritis?
Authors: H Ohta, S Shirai, K Nasu, M Tei, H Kambara, T Ono, M Shintaku
Journal: Clinical Nuclear Medicine (1998)

Ga-67 scintigraphy was performed in a 56-year-old woman with Wegener's granulomatosis. Abnormal uptake in the nasal cavity, kidneys, and the aortic arch was seen. CT showed thickening of the aortic wall, and overlap with Takayasu's arteritis was suspected. This case might be a polyangiitis overlap syndrome.
Observations on the Treatment of Salicylism in Children
Authors: Stanford B. Friedman, Joseph F. Stocks
Journal: New England Journal of Medicine (1961)

THE child with salicylism represents a difficult management problem, and recent therapeutic suggestions have included sodium bicarbonate administration,1 , 2 acetazolamide,3 exchange transfusion,4 5 6 7 peritoneal dialysis8 , 9 and hemodialysis.10 11 12 We have reviewed our experiences on the Children's Medical Service to compare such therapeutic approaches with management based on certain general principles outlined by Talbot, Richie and Crawford.13 Their therapy takes advantage of the body's homeostatic mechanisms to achieve and then to maintain metabolic normalcy when fluids and electrolytes are provided at rates that fall within limits of physiologic tolerance. From a total of 29 patients seen during the period 1955–1960 and considered ill enough . . .
Patient Access to Medical Devices — A Comparison of U.S. and European Review Processes
Authors: Saptarshi Basu, John C. Hassenplug
Journal: New England Journal of Medicine (2012)

Interview with Dr. Rita Redberg on the approval process for medical devices in the United States and in Europe. (00:00)Download The U.S. process for approving innovative, high-risk medical devices has been criticized for taking longer than the European process. But a review of the data suggests that it takes the same amount of time or less for U.S. patients to gain access to such devices.
An unusual case of invasive Blastocystis hominis infection
Authors: S. Janarthanan, N. Khoury, F. Antaki
Journal: Endoscopy (2011)

A 47-year-old African-American man presented with 3-week history of rectal bleeding. It had started 6 weeks previously while he was visiting Nigeria, with watery diarrhea, abdominal bloating, and pain. His symptoms had resolved without treatment within 2 weeks. Physical examination and hematological and biochemical profiles were all normal. Colonoscopy showed several large ulcers in the cecum, hepatic flexure, and transverse colon with normal surrounding mucosa ([Fig. 1]), and multiple small, shallow ulcers in the rectum ([Fig. 2]). Pathologic examination of biopsies showed exudates with necrosis, and pieces of colonic mucosa with severe acute and chronic inflammation, and focal acute cryptitis, plus multiple vacuolated and amoeboid structures ([Fig. 3]). Subsequent stool study with a special trichrome stain confirmed the diagnosis of Blastocystis hominis. He was treated with metronidazole for 10 days with symptom resolution, and no recurrence of diarrhea.
Abstract 2099: Novel inhibitors of NFkB inducing kinase (NIK) are cytotoxic for myeloma cell lines with NIK-dependent activation of NFkB.
Authors: Yulia N. Demchenko, Walter Michael Kuehl
Journal: Cancer Research (2013)

Abstract NFkB activity is critical for survival and proliferation of normal lymphoid cells and many kinds of B-cell tumors, including multiple myeloma (MM). NFkB activating mutations, which are apparent progression events, enable MM tumors to become less dependent on bone marrow signals that activate NFkB. Mutations that activate NFkB-inducing kinase (NIK) protein are the most prevalent among the many kinds of NFkB mutations in MM tumors. NIK is the main activating kinase of the alternative NFkB pathway, although over-expression of NIK also can activate the classical pathway. Three Amgen compounds (two NIK inhibitors and an isomeric control) were tested with human myeloma cell lines. These specific NIK inhibitors are selectively cytotoxic for cells with NIK-dependent activation of NFkB. The combination of NIK-inhibitors with IKKβ-inhibitors or dexamethasone show a synergistic effect that might more efficiently target some MM tumors. Citation Format: Yulia N. Demchenko, Walter Michael Kuehl. Novel inhibitors of NFkB inducing kinase (NIK) are cytotoxic for myeloma cell lines with NIK-dependent activation of NFkB. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2099. doi:10.1158/1538-7445.AM2013-2099 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract PL02-01: A systems biology approach to integrative cancer genomics
Authors: Andrea Califano
Journal: Cancer Research (2011)

Abstract The recent onslaught of molecular data across multiple human malignancies is producing an unprecedented repertoire of genetic and epigenetic alterations contributing to tumorigenesis and progression. Yet, the direct impact of this knowledge on tumor treatment and prevention is still largely unproven. Loss of tumor suppressor function is difficult to target pharmacologically and, with a handful of exceptions, alterations providing potential drug targets are relatively infrequent in cancer patients and are thus unlikely to support clinical development. By reconstructing and interrogating the regulatory logic of the cancer cell, which is responsible for integrating multiple aberrant signals in vivo, systems biology is starting to elucidate broad addiction mechanisms, both oncogene and non-oncogene based that are exquisitely specific to the cancer subtype. In this presentation, we will discuss recent result in the discovery of synergistic, non-oncogene addiction mechanisms in high-grade glioma, of the upstream genetic alterations causally related to their functional activation, and of candidate targets for combination therapy. This approach has been generalized to a number of additional tumor subtypes and provides a novel framework for cancer target discovery and development in patient-centric fashion. 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 PL02-01. doi:10.1158/1538-7445.AM2011-PL02-01
RISK FOR SILENT CEREBRAL EVENTS IN PATIENTS UNDERGOING ATRIAL FIBRILLATION ABLATION
Authors: Thomas Deneke, Karin Nentwich, Joachim Krug, Rainer Schmitt, Goergios Kristopoulos, Philipp Halbfass, Andreas Muegge, Attilla Szöllösi, Anja Schade, Patrick Müller
Journal: Journal of the American College of Cardiology (2015)
EXPERIENCE OF PERCUTANEOUS LEFT ATRIAL APPENDAGE SUTURE LIGATION: RESULTS FROM A UNITED STATES MULTICENTER EVALUATION
Authors: Muhammad Rizwan Afzal, Randall Lee, Hosakote Nagaraj, David Tschopp, Brett Gidney, Christopher Ellis, Saibal Kar, Varuna Gadiyaram, Rudolph Evonich, Abdi Rasekh, Jie Cheng, Frank Cuoco, Sheetal Chandhok, Sampath Gunda, Sandia Iskandar, Madhu Reddy, Donita Atkins, Sudharani Bommana, Phillip Cuculich, Douglas Gibson, Jayant Nath, Matthew Earnest, David Wilber, Dhanunjaya Lakkireddy
Journal: Journal of the American College of Cardiology (2016)
Long-Acting Gonadotropin-Releasing Hormone Implant to Maintain Medical Castration for Two Years in Men with Prostate Cancer
Authors: Irving M. Spitz, Boris Chertin, Tzina Lindenberg, Amicur Farkas
Journal: New England Journal of Medicine (1999)

To the Editor: Cassileth et al. (Dec.3 issue) 1 report the results of a large study comparing chemotherapy with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission.Their study showed that autologous or allogeneic bone marrow transplantation offered no advantage over intensive chemotherapy in terms of overall survival.However, the study included patients with a variety of risk factors.Although there is no established prognostic index for acute myeloid leukemia, we believe that most institutions do not perform bone marrow transplantation in patients with either the M2 or the M3 type of acute myeloid leukemia in first remission, according to the French-American-British (FAB) classification, unless there are unfavorable factors, such as a high initial white-cell count or difficulty in achieving remission.What we want to know is, who really requires bone marrow transplantation in first remission?In other words, for which patients should we reserve bone marrow transplantation until they have a relapse?Characterizing the patients who have had relapses with chemotherapy and in whom bone marrow transplantation as second-line therapy has failed will be informative in identifying eligible patients for further randomized studies.In such patients, bone marrow transplantation as consolidation therapy may be of benefit.
Abstract 3349: Transformation of mammary epithelial cells by inactivation of p53 and PTEN generates cancer stem cells driven by an IL-6/TGF-beta inflammatory loop
Authors: Korkaya Hasan, Gwangil Kim, Fayaz Malik, April Davis, Amanda K. Paulson, Ahmet A. Quraishi, Rosemarie C. D'Angelo, Nader Tawakkol, Suling Liu, Khaled Hassan, Shawn G. Clouthier, Max S. Wicha
Journal: Cancer Research (2012)

Abstract The PTEN and p53 tumor suppressor genes, frequently inactivated in human breast cancers have been shown to be regulators of normal and malignant breast stem cell self-renewal. In addition, inactivation of tumor suppressors in preneoplastic lesions are implicated in tumor progression from ductal situ in carcinoma (DCIS) to invasive ductal carcinoma. To determine the relationship between stem cell self-renewal and carcinogenesis, we examined the effects of PTEN and p53 knockdown on normal mammary epithelial cells obtained from reduction mammoplasties, as well as in the non-transformed mammary cell line MCF10A. Simultaneous knockdown of PTEN and p53 in normal mammary epithelial cells generated hyperplastic and DCIS-like lesions when these cells were transplanted into the humanized mammary fat pads of NOD/SCID mice. In MCF10A cells knockdown of PTEN and p53 synergized to expand the stem cell compartment transforming these cells and generating highly metastatic tumors in NOD/SCID mice. Stem cell expansion was driven by activation of an inflammatory loop involving both IL-6 and TGF-b. This inflammatory loop was mediated by both AKT/b-Catenin and Stat3/NF-kB pathways. Conversely collective inhibition of these pathways including TGF-b, IL-6 and Wnt/b-Catenin and Stat3/NF-kB was necessary to revert back this stem cell phenotype. This may suggest that synergistic activity of these pathways may contribute to the expansion and transformation of mammary stem cells. The expanded cancer stem cells were highly metastatic and invasive and displayed properties of EMT. The IL6-R antibody tocilizumab blocked this loop resulting in a reduction of CSCs and thus inhibiting tumor growth in mouse xenografts. These studies suggest that loss of PTEN and p53 transforms mammary epithelial cells by activating an inflammatory loop mediated by IL-6 and TGF-b, generating CSCs with an EMT phenotype. Since CSCs drive tumor growth and metastasis, targeting the self-renewal by interfering with this CSC, inflammatory loop represents a rational strategy for breast cancer prevention and therapy. 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 3349. doi:1538-7445.AM2012-3349