tbuckley/cabot-search huggingface dataset:
Abstract P2-12-13: Results of randomised controlled phase II study (KBCSG02 trial) of the efficiency of palonosetron, aprepitant, and dexamethasone for day1 with or without dexamethasone on days2 and 3.
Authors: Y Kosaka, N Sengoku, M Kikuchi, H Nishimiya, T Enomoto, M Kuranami, M Watanabe
Journal: Cancer Research (2012)

Abstract Background: Emesis is one of the major non-hematologic toxicity caused by chemotherapy. The control of Chemotherapy Induced Nausea and Vomiting (CINV) is conducted to a life lengthening. Recently, CINV is controlled by the second generation 5-HT3 receptor blocker (Palonosetron; PALO) and a NK-1 receptor antagonist (Aprepitant; APR). It has been shown that dexamethasone (DEX) with 5-HT3 receptor blocker improves acute/delayed CINV. However, it has not been determined the medication schedule of DEX with PALO and APR. The purpose of this study is evaluated the efficiency of palonosetron, aprepitant and dexamethasone for day1 with or without dexamethasone on days2 and 3. Methods: Breast cancer patients who administered anthracyclin drug regimen have been eligible from April, 2011 to June, 2012. The patients were randomised to group A (PALO/APR/DEX one day) and group B (PALO/APR/DEX three days). Eighty patients was estimate as study samples. The primary endpoint was a complete response (CR) rate of vomiting, the secondary endpoint was a complete control (CC) rate of vomiting. Results: Forty patients were enrolled in this study, and patient recruitment is continued. CR rate was no significant difference in both groups (76.9% of group A, 73.3% of group B). CC rate of group A (61.5%) did not show inferiority compared with group B (40.0%). Conclusions: In this current study, we suggest that one day dexamethasone treatment could reduce enough the emesis of high emetogenic chemotherapeutic agents. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-13.
Primary Testicular Serous Papillary Carcinoma With Extensive Calcification on CT and FDG PET/CT
Authors: Dengjun Sun, Rong Yu, Dongmei Geng, Jian Chen, Liangming Zhang
Journal: Clinical Nuclear Medicine (2014)

A 67-year-old man with a swollen right testicle also had dry cough for 3 months. Computed tomography of the chest showed multiple calcified lung nodules and lymph nodes in the hilum. FDG PET/CT revealed elevated FDG activity not only in the right testicle mass but also calcified thoracic lesions. Histologic examination after testicle biopsy demonstrated primary testicular papillary serous carcinoma.
PMO-234 Is the Rutgeerts' score of any clinical value after ileo-colic resection for Crohn's disease? A prospective study in district general hospital practice: Abstract PMO-234 Table 1
Authors: B D Warner, L Blackmore, P Blaker, A Harris
Journal: Gut (2012)

<h3>Introduction</h3> Disease recurrence after surgical resection for Crohn9s disease (CD) is observed in 20%–30% of patients at 1 year, with a 10% increase per year in subsequent years. The European Crohn9s and Colitis Organisation currently recommends ileo-colonoscopy 1 year after ileo-colic resection, since this predicts the need for further surgery (Statement 8C) within 2 years.<sup>1</sup> This statement is not supported by the BSG guidelines, highlighting a need for prospective studies to determine the role of the Rutgeert9s score following ileo-colic resection. The aim of this study was to determine if the Rutgeert9s score<sup>3</sup> at 1–2 years after ileo-colic resection predicts clinical recurrence and/or need for further surgery in patients with CD in district general hospital practice. <h3>Methods</h3> Between 2005 and 2011, 43 patients with fibrostenotic or penetrating terminal ileal or right sided CD underwent ileo-colic resection. Ileo-colonoscopy was performed in 34 asymptomatic patients between 1 and 2 years following surgery. A single expert observer (AWH) assessed the surgical anastomosis to determine the Rutgeerts9 score<sup>3</sup> (i<sub>0</sub>–i<sub>4</sub>). Nine patients who underwent resection were excluded either because ileo-colonoscopy was unsuccessful or the patient refused endoscopic assessment. <h3>Results</h3> 14 of 15 (93%) patients with Rutgeert9s scores i<sub>0</sub> or i<sub>1</sub> remained asymptomatic from CD (Harvey Bradshaw Index ≤4) at January 2012 (range of follow-up 4–69 months, mean of 30 months after ileo-colonoscopy). Three (20%) of these patients smoked. Of 19 patients scoring i<sub>2</sub> to i<sub>4</sub>, 12 (63%) had clinical recurrence requiring medical treatment with immunosuppression and/or biologics. 47% of patients with a Rutgeert9s score of i2–i4 and 50% of those with clinical recurrence were current smokers. <h3>Conclusion</h3> In district general hospital practice, a low Rutgeert9s score (i<sub>0</sub> or i<sub>1</sub>) at 1–2 years after ileo-colic resection for CD predicts prolonged clinical remission without the need for medical treatment. By contrast, in those patients with a Rutgeert9s scores ≥i<sub>2</sub> clinical recurrence occurred within a maximum of 16 months following surgical resection with a higher rate of recurrence among smokers. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Van Assche G</b>. The second European evidence-based Consensus on the diagnosis and management of Crohn9s disease: Special situations. <i>J Crohns Colitis</i> 2010;<b>4</b>:63–101. 2. BSG IBD Guidelines 2011:6.6.3 Postoperative management: preventing postoperative recurrence. 3. <b>Rutgeerts P</b>, Geboes K, Vantrappen G. Natural history of recurrent Crohn9s disease at the ileocolonic anastomosis after curative surgery. <i>Gut</i> 1984;<b>25</b>:665–72.
Abstract 894: Melanoma fights cisplatin with NO: S-nitrosation as a mechanism supporting drug-resistance.
Authors: Luiz C. Godoy, Chase C.T. Anderson, Rajdeep Chowdhury, Laura J. Trudel, Gerald N. Wogan
Journal: Cancer Research (2013)

Abstract Melanoma patients experience inferior survival after bio-chemotherapy when their tumors contain numerous cells expressing the inducible isoform of NO synthase (iNOS), and elevated levels of nitrotyrosine, a product derived from nitric oxide (NO). Although several lines of evidence suggest that NO promotes tumor growth and increases resistance to chemotherapy, it is unclear how it shapes these outcomes. Here we demonstrate that modulation of NO-mediated S-nitrosation of cellular proteins is strongly associated with the pattern of response to the anti-cancer agent cisplatin in human melanoma cells in vitro. Cells were shown to express iNOS constitutively, and to generate sustained nanomolar levels of NO intracellularly. Inhibition of NO synthesis or scavenging of NO enhanced cisplatin-induced apoptotic cell death. Additionally, pharmacologic agents disrupting S-nitrosation markedly increased cisplatin toxicity, whereas treatments favoring stabilization of S-nitrosothiols decreased its cytotoxic potency. Activity of the pro-apoptotic enzyme caspase-3 was higher in cells treated with a combination of cisplatin and chemicals that decreased NO/S-nitrisothiols, whereas lower activity resulted from cisplatin combined with stabilization of S-nitrisothiols. Constitutive protein S-nitrosation in cells was detected by analysis with biotin switch and reduction/chemiluminescence techniques. Moreover, intracellular NO concentration increased significantly in cells that survived cisplatin treatment, resulting in augmented S-nitrosation of caspase-3 and prolyl-hydroxylase-2 (PHD2), the enzyme responsible for targeting the pro-survival transcription factor HIF-1α for proteasomal degradation. Because activities of these enzymes are inhibited by S-nitrosation, our data thus indicate that modulation of intrinsic intracellular NO levels substantially affects cisplatin toxicity in melanoma cells. The underlying mechanisms may thus represent potential targets for adjuvant strategies to improve the efficacy of chemotherapy. Citation Format: Luiz C. Godoy, Chase C.T. Anderson, Rajdeep Chowdhury, Laura J. Trudel, Gerald N. Wogan. Melanoma fights cisplatin with NO: S-nitrosation as a mechanism supporting drug-resistance. [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 894. doi:10.1158/1538-7445.AM2013-894
Hepatitis C–Related Primary Effusion Lymphoma of the Pleura and Peritoneum, Imaged With F-18 FDG PET/CT
Authors: William Makis, Jerry Stern
Journal: Clinical Nuclear Medicine (2010)

Primary Effusion Lymphoma (PEL) is a rare form of Non-Hodgkin lymphoma that involves serous body cavities (pleural, pericardial, or peritoneal) with lymphomatous effusions in the absence of lymphadenopathy or organomegaly. Although it was seen mostly in HIV-positive patients, it has recently been reported in HIV-negative patients with chronic Hepatitis B or C infections. PEL is associated with human herpes virus type-8 infection, often presents with rapidly progressive effusions and generally has a poor prognosis. This is a case of a 65-year-old HIV-negative man with Hepatitis C cirrhosis, who presented with abdominal pain. An F-18 FDG PET/CT showed marked ascites and pleural effusions with increased F-18 FDG uptake in the pleura and peritoneum on the left side. Analysis of the cells in the peritoneal fluid revealed a human herpes virus 8-positive PEL of the peritoneum. As a result the patient was no longer considered a liver transplant candidate and died 2 weeks after the diagnosis.
Abstract 4558: Discovery and mechanistic studies of novel class of CXCR2 inhibitors.
Authors: Helen Ha, Nouri Neamati
Journal: Cancer Research (2013)

Abstract Background: Chemokine receptor, CXCR2 is expressed on various immune cells and is essential for neutrophil recruitment and angiogenesis at sites of acute and chronic inflammation caused by tissue injury or infection. Due to its role in inflammation, it has been implicated in a number of inflammation-mediated diseases such as psoriasis, arthritis, COPD, cystic fibrosis, and asthma. More recently, it is also implicated in various types of cancer. CXCR2 and its ligands are up-regulated in cancer cells as well as the tumor microenvironment and have been shown to promote tumor growth, angiogenesis and invasiveness. Though pharmaceutical companies have pursued the development of CXCR2-specific small-molecule inhibitors as anti-inflammatory agents within the two past decades, there are currently no clinically approved CXCR2 inhibitors. Methodology/Principal Findings: Using a high-throughput, cell-based, CXCR2 assay, we screened an in-house library of structurally diverse compounds and identified a novel class of CXCR2 biased ligand. Our lead compound, CX797, inhibited IL8-mediated cyclic AMP signaling and receptor degradation, while specifically up-regulating IL8-mediated β-arrestin recruitment and MAP kinase signaling. CX797 also inhibited Jurkat cell proliferation via G0/G1 cell cycle arrest. Conclusions/Significance: In our studies we have identified a novel class of CXCR2 ligand, CX797, and the first to report biased CXCR2 ligand signaling. Mechanistic studies of CX797 and previously reported CXCR2 inhibitor, SB265610, show these two classes have distinct mechanism of action on CXCR2. CX797 is a potential candidate for further optimization and development for various inflammatory diseases and CXCR2-expressing cancer. Citation Format: Helen Ha, Nouri Neamati. Discovery and mechanistic studies of novel class of CXCR2 inhibitors. [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 4558. doi:10.1158/1538-7445.AM2013-4558
AB0053 Increased Frequency of Plasmacytoid Dentritic Cells in Rheumatoid Arthritis Patients in Response to IL-6R Blockade
Authors: Y.-M. Pers, J. Quentin, P. Le Blay, C. Jorgensen, P. Louis-Plence
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that can induce either immunity or tolerance. Myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) represent the 2 major subsets of DCs, with human pDCs defined as CD4<sup>+</sup>CD11c<sup>-</sup>CD123<sup>hiCD1c-</sup>CD303<sup>+HLADR+</sup> cells, and mDCs defined as CD4<sup>+</sup>CD1c<sup>+CD123lo</sup>CD303<sup>-</sup>CD45RO<sup>-</sup>HLADR<sup>+</sup> cells. Some studies reported that patients with therapy-induced remission of rheumatoid arthritis (RA) exhibited higher numbers of circulating pDCs. <h3>Objectives</h3> Indeed, <i>in vivo</i> effects of IL-6 inhibition on DCs are partially unknown. Tocilizumab (TCZ) is the first therapeutic agent targeting IL-6 to be effective in RA. Our aim was to monitor the changes in circulating mDCs and pDCs during TCZ therapy in patients with RA. <h3>Methods</h3> DC subsets were characterized by flow cytometry in the peripheral blood of patients with RA (n=15) and in healthy volunteers (n=10). In patients with RA, these levels were measured before and during TCZ therapy (8 mg/kg every 4 weeks). Response to TCZ therapy was evaluated at 12 weeks. All the patients fulfilled the 1987 ACR criteria for RA. At baseline, the mean DAS28 score was 5.2 (±1.3). At 3 months, 9 patients were classified as responders (DAS28 1.8±0.8) and 6 patients were classified as non-responders (DAS28 4.0±0.4). Statistical analyses were performed by Mann-Whitney U tests or Wilcoxon signed-rank tests. <h3>Results</h3> At baseline, patients with active RA were characterized by a significantly decrease frequency of circulating pDCs compared to healthy donors (40.2% vs 60.9%; p&lt;0.01). After 3 months of TCZ therapy, pDC frequency has not changed (48.5% vs 40.2%) while mDC frequency decrease significantly (31.1% vs 22.3%; p&lt;0.05). Moreover, TCZ-treated patients who reached low disease activity at Week 12 had significant increase frequency of pDC (52.0% vs 38.7%; p&lt;0.05) as compared with non-responders patients (43.2% vs 42.5%). <h3>Conclusions</h3> Our study reveals an increased frequency of circulating pDC in responder patients to TCZ therapy. We previously demonstrated that the clinical response was also associated with increased frequencies of CD39<sup>+</sup> Treg cells. Our results suggest a crosstalk between DC and Tregs to restore/induce tolerance. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4336
A3.7 No evidence of cathelicidin being involved in the pathogenesis of lupus and arthritis
Authors: D. Kienhoefer, I. Schubert, J. Hahn, Èlia Bosch, C. Sjöwall, B. Agerberth, G. Schett, M. Hoffmann
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Antimicrobial peptides (AMPs) such as cathelicidins have a well known role in the immune defence against pathogens. In the last years a contributory impact of AMPs was also reported in the pathogenesis of autoimmune diseases. Therefore, the aim of this project was to examine the impact of cathelicidins on the pathogenesis of lupus and arthritis using animal models and sera from patients. <h3>Methods</h3> Pristane-induced lupus (PIL) was induced by intraperitoneal injection of 500 µl pristane (2, 6, 10, 14-tetramethyl-pentadecane) in female C57BL/6 WT and cathelicidin-related antimicrobial peptide (CRAMP<sup>-/-</sup>) mice. Autoantibody levels of anti-Sm/RNP, anti-dsDNA and anti-histone were measured via ELISA, serum cytokine levels were determined via FlowCytomix<sup>TM</sup> Multiplex. Pathological changes in lungs and kidneys isolated from mice at day 14 and 180 after pristane injection were analysed by histology. Collagen-induced arthritis (CIA) was induced in male WT and CRAMP<sup>-/-</sup>mice and arthritis severity was visually scored. Histomorphometrical analysis was done by OsteoMeasure<sup>TM</sup> software and included parameters of inflammation, cartilage degradation, and bone erosion. Serum LL-37 and anti-LL-37 levels were measured by ELISA in healthy donors and patients with SLE, RA, and Sjögren syndrome. <h3>Results</h3> No differences in the serum-levels of anti-Sm/RNP, anti-dsDNA, and anti-histone autoantibodies or of various cytokines could be observed between WT and CRAMP<sup>-/-</sup> mice after pristane-injection. Furthermore, the lung and kidney pathology did not differ between WT and CRAMP-deficient mice. Onset of CIA was slightly delayed in CRAMP<sup>-/-</sup> mice, but at later time points, arthritis incidence or severity was not higher in WT mice compared to CRAMP<sup>-/-</sup>. Histomorphometry revealed no differences between WT and CRAMP<sup>-/-</sup> mice. Although serum levels of anti-LL-37 were significantly higher in patients with SLE compared to healthy donors or patients with RA or Sjögren´s syndrome, no correlation to levels of type I Interferons or to disease activity could be observed. <h3>Conclusions:</h3> Although levels of cathelicidins were upregulated in mouse models of lupus and arthritis, cathelicidin-deficiency did not persistently affect the course of the diseases. Also in patients with SLE, we did not find any evidence that autoantibodies against cathelicidins directly influence disease activity or severity. Reactivity against cathelicidins in lupus and arthritis could thus be an epiphenomenon caused by extensive overexpression in blood and affected tissues. In addition, other cationic AMPs could functionally compensate for the deficiency of cathelicidins.
SAT0082 Incidence and Survival of Biopsy-Proven GIANT Cell Arteritis in Northern Italy
Authors: P. Macchioni, M. Catanoso, L. Boiardi, F. Muratore, G. Restuccia, I. Chiarolanza, A. Cavazza, F. Luberto, C. Salvarani
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To investigate the incidence and mortality of biopsy proven giant cell arteritis (GCA) over a 27-year period in a defined area of northern Italy. <h3>Methods</h3> All patients with incident GCA diagnosed from January 1, 1986 to December 31, 2012 living in the Reggio Emilia area were identified through computerized hospital discharge diagnosis and a structured review of all histopahology reports. Patients were followed up from the time of diagnosis until either their death or December 31, 2013. <h3>Results</h3> Two hundred and eighty-seven patients (76 men and 211 women) had biopsy proven GCA according to the histopathological examination. Mean±SD age at diagnosis was 74.3±7.4 years. The mean annual incidence rate (IR) of GCA was 23.08/10<sup>6</sup> (95% CI: 20.5-25.9). The mean IR was 33.3/10<sup>6</sup> (95% CI: 29.0-38.1) among women and 12.4/10<sup>6</sup> (95% CI: 9.8-15.5) for men (p not significant). The lowest IR occurred in male patients in the 50-59 years age group (5.13/10<sup>6</sup>; 95% CI: 1.4-13.1), the highest IR was observed in female patients 70-79 years age group (153.6/10<sup>6</sup>; 95% CI: 124.7-187.2). IR difference between sex was significant only in the 60-69 age group (IR male/female 14.6/67.1,95% CI 7.0-26.9 vs 49.8-88.4). The average annual IR increased from 5.63/10<sup>6</sup> during 1986-1988 to 45.23/10<sup>6</sup> during 1998-2000 period and was stable thereafter with IR of 30-23/10<sup>6</sup>.At histological examination 13.6% (39 pts) had only small vessels perivascular involvement (adventitial vasa vasorum and peri-adventitial capillaries). Prevalence of small vessels involvement was significant higher among male patients (male 30% vs 7%female, p&lt;0.001).One hundred and twenty-one patients (42.2%) died during the follow-up period (median survival after diagnosis 152 months [range 4-320 months]). Survival did not differ nor between gender or between different histopathological pattern. <h3>Conclusions</h3> This population-based study is the first to report the incidence of biopsy proven GCA in Italy. Our average annual IR is similar to that reported in the period 1984-1988 in Finland (1). Unlike the Spanish data our annual IR is higher among women than among men (2). <h3>References</h3> Franzén P, Sutinen S, von Knorring J. Giant cell arteritis and polymyalgia rheumatica in a region of Finland: an epidemiologic, clinical and pathologic study, 1984-1988. J Rheumatol. 1992;19:273-6. Gonzalez-Gay MA, Miranda-Filloy JA, Lopez-Diaz MJ, Perez-Alvarez R, Gonzalez-Juanatey C, Sanchez-Andrade A, Martin J, Llorca J. Giant cell arteritis in northwestern Spain: a 25-year epidemiologic study. Medicine (Baltimore). 2007;86:61-8. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5523
Abstract 301: 67-kDa laminin receptor as prognostic marker and therapeutic target in epithelial ovarian carcinoma
Authors: Jeong-Won Lee, Young-Jae Cho, Chel-Hun Choi, Young Ae Park, Jung-Joo Choi, Hye-Kyeong Jeon, Byoung-Gie Kim, Duk-Soo Bae
Journal: Cancer Research (2011)

Abstract Objectives: The 67-kDa laminin receptor (67LR) is a non-integrin cell surface receptor with high affinity for laminin, which plays a key role in tumor invasion and metastasis. We investigated the clinical significance of 67LR expression including roles of prognostic marker or therapeutic target in epithelial ovarian carcinoma. Methods: The expression of 67LR was evaluated by immunohistochemistry in 71 patients with ovarian carcinomas including 54 serous, 13 endometrioid and 4 mucinous types. We assessed the correlation of 67LR expression with clinical characteristics including histology, tumor grade, FIGO stage, and survival. In vitro experiment was performed for 67LR with inhibition using siRNA to evalute its role in cell growth control and sensitivity to chemotherapeutic agents in ovary carcinoma cell line. Results: The expression of 67LR protein with mainly membranous location was observed in majority (45/62, 73 %) of the EOCs but not in normal ovarian tissues (P&amp;lt;0.001). Thirty (48.4%) of 62 specimens were scored as cytoplasmic-67LR-positive. The 67-LR membranous expression was correlated with poorer progression-free survival (HR = 2.14, 95% CI 1.08-4.23, P = 0.028), though it was not an independent prognostic factor. And interestingly, cytoplasmic expression without membranous expression was correlated with poorer overall survival (P = 0.002). When 67-LR siRNA was transfected to several ovarian cancer cells, there was significant in vitro effect on cell survival and proliferation assessd by MTT assay. Conclusion: These finding suggest that 67LR expression might be a prognostic marker for survival and it may play possible target for experimental treatment of epithelial ovary carcinoma. 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 301. doi:10.1158/1538-7445.AM2011-301