tbuckley/cabot-search huggingface dataset:
FRI0176 Group Clinics for Rheumatoid Arthritis: A New Model of Care: Table 1.
Authors: F. Birrell
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Group clinics are an alternative model of care to 1:1 clinic appointments. They have been used extensively in the United States for diverse conditions, including diabetes &amp; hypertension, but have not been used for inflammatory arthritis, or to any great extent in Europe. <h3>Objectives</h3> The objectives of this study were to establish the feasibility of group clinics for inflammatory arthritis patients and whether they allow collection of data on key disease outcomes. <h3>Methods</h3> Follow up patients with inflammatory arthritis were offered a group clinic, as an alternative to conventional consultant outpatient review. Patients completed a multidimensional health assessment questionnaire and had tender and swollen joints counted on arrival. The group consultation itself included ground rules, selection of topics and discussion. Injections, treatment changes or confidential issues were dealt with after the main session. <h3>Results</h3> There were 894 patient attendances at 58 clinics (mean clinic size 15). The sessions were feasible and productive. DAS28 and HAQ scores could be calculated and recorded. The following management options were available: parenteral steroid, joint injection, DMARD change, anti-inflammatories, referrals. Nearly all patients reported they would recommend group clinics to others. Median (interquartile range) evaluation data were as follows: <h3>Conclusions</h3> Group clinics can work in the UK &amp; could be tried across Europe. Patients enjoy them and this study has provided evidence that key outcomes can be collected. The group clinic provides a novel model for both monthly review of early Rheumatoid Arthritis and annual review of stable disease. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4720
Malignant Extrarenal Rhabdoid Tumor of the Spine
Authors: William Makis, Anthony Ciarallo, Marc Hickeson
Journal: Clinical Nuclear Medicine (2011)

Malignant extrarenal rhabdoid tumor (ERRT) is a very rare type of soft-tissue sarcoma with a reported incidence of 0.3% of all soft-tissue sarcomas. Only 7 cases of spinal malignant ERRT have been reported in the literature, and to our knowledge, F-18 FDG PET/CT imaging for staging and evaluation of response to therapy for these tumors has not been previously described. This is a case of an 8-month-old boy with malignant ERRT of the spine, who was staged with F-18 FDG PET/CT, and had his tumor burden assessed with PET/CT after chemotherapy, which altered the subsequent chemotherapy regimen.
Abstract 1854: Lysophosphatidic Acid Acyltransferase-Beta contributes to proliferation and anchorage-independent growth in pancreatic adenocarcinoma
Authors: Michelle Blaskovich, Harsukh Gevariya, Nicholas J. Lawrence, Saïd M. Sebti, Gregory Springett
Journal: Cancer Research (2012)

Abstract Abstract: Lysophosphatidic acid acyltransferase-beta (LPAAT-α) catalyzes the production of phosphatidic acid (PA) from lysophosphatidic acid (LPA). PA is a lipid cofactor that contributes to the activation of c-Raf, BRAF, mTOR and PKC-α. LPAAT-α expression is a prognostic factor in gynecologic malignancies and is being investigated as a therapeutic target in a variety of tumor types. We previously reported that LPAAT-α is expressed in pancreatic cancer cell lines and in human pancreatic adenocarcinoma tissues. We employed siRNA knockdown of LPAAT-α expression in pancreatic cancer cells in vitro. We find that reduction in the expression of LPAAT-α protein is associated with decreased proliferation and impairment in anchorage dependent growth of pancreatic cancer cells. Methods: MiaPaCa and Panc-1 cells were transfected with two different siRNAs targeted to LPAAT-α at 10 nM and 25 nM for 48 hrs and 72 hrs. A non-targeting siRNA was used as a control. The cells were then plated on tissue culture dishes or in soft agar and allowed to proliferate. Proliferation on plastic dishes was measured using Alamar Blue. Colony formation in soft agar was determined by directly counting macroscopic colonies. Results: Transfection of MiaPaCa and Panc-1 cells with siRNA at 25 nM for 72 hours achieved almost 100% inhibition of LPAAT-α protein expression by Western blotting. Under these conditions there was a 50% reduction in proliferation and colony formation. Studies to determine the effects of depleting LPAAT-α on the levels of p-PKC-α, p-MEK, p-4E-BP1 and p-S6Kinase are ongoing and will be presented. Conclusions: Suppression of expression of LPAAT-α protein in pancreatic cancer cell lines reduces proliferation and anchorage independent growth. This contributes to the validation of LPAAT-α as a therapeutic target in pancreatic cancer. 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 1854. doi:1538-7445.AM2012-1854
A randomized, double-blind, placebo-controlled, phase 3 study of rituximab with or without ibrutinib for Waldenstrom’s macroglobulinemia (PCYC-1127-CA).
Authors: Meletios A. Dimopoulos, Xavier Leleu, Jeffrey Matous, David MacDonald, Judith Trotman, Albert Oriol, Chaim Shustik, Alessandra Tedeschi, Ramon Garcia-Sanz, Leonard T. Heffner, Shuo Ma, Beatrice Mahe, Constantine Tam, Olivier Tournilhac, Jianling Li, Priyanka Singh, Elizabeth Bilotti, Thorsten Graef, Steven P. Treon, Christian Buske
Journal: Journal of Clinical Oncology (2015)

TPS8599 Background: Current treatments for Waldenstrom’s macroglobulinemia (WM) are not curative, and a standard of care does not exist. A highly recurrent somatic mutation in WM, MYD88 L265P, signals through interleukin-1 receptor-associated kinase 1 and Bruton’s tyrosine kinase (BTK) to mediate the constitutive activation of the NF-κB pathway (Yang, 2013). Ibrutinib (ibr), an oral inhibitor of BTK, impairs crosstalk between MYD88 and BTK, and blocks BTK dependent downstream signaling within the B-cell receptor pathway inducing apoptosis of WM cells (Treon, 2012).Thus, ibr offers a novel therapeutic approach for pts with WM. Pts with previously treated WM receiving different ibr doses achieved durable responses in a phase (Ph) 1 study (Advani, 2013). This was confirmed in a Ph 2 trial of ibr 420 mg daily (overall response rate [ORR] of 87%; Treon, 2014) leading to the first FDA approval in WM. Ibr + rituximab (rtx) showed activity and tolerability in high-risk CLL and MCL. This Ph 3 study evaluates the safety and efficacy of ibr + rtx vs. placebo + rtx in pts with WM. Methods: Approximately 150 pts will be randomized in a 1:1 ratio to receive rtx 375 mg/m2 IV weekly for 4 weeks, followed by a second 4-weekly rtx course 3-months later, and either ibr 420 mg daily or matching placebo until progressive disease (PD) or unacceptable toxicity. Key inclusion criteria include WM with documented PD or no response (stable disease) to last treatment if previously treated; symptomatic disease requiring treatment per the 2nd International Workshop on WM; and adequate hematologic, hepatic, and renal function. Exclusion criteria include CNS involvement and clinically significant cardiovascular disease. Pts refractory to the last rtx-containing therapy excluded from the randomized study are eligible for the open-label single-agent ibr substudy (n = 30). The primary endpoint is progression-free survival assessed by an independent review committee. Secondary endpoints are ORR, overall survival, hematologic improvement, time to next treatment, and safety. Pts in the control arm may receive single-agent ibr after confirmation of PD. Enrollment began in July 2014 (NCT02165397). Clinical trial information: NCT02165397.
Abstract 3238: A novel natural product disrupts androgen receptor signaling in prostate cancer cells.
Authors: Karishma Amin, Shankar Jagadeesh, Nabin Barua, Samir Bhattacharya, Partha P. Banerjee
Journal: Cancer Research (2013)

Abstract Continued reliance on androgen receptor (AR) signaling is a hallmark of prostate cancer, including the development of castration-resistant prostate cancer (CRPC), making it an attractive therapeutic target for prostate cancer treatment. Mahanine is a novel carbazole alkaloid derived from the leaves of Murraya koenigii, commonly known as the curry leaf plant, which grows widely across East Asia. We have reported previously that mahanine possesses the ability to inhibit prostate cancer cell growth. Since sustained AR signaling is associated with the development of CRPC, we investigated the effect of mahanine treatment on AR signaling in prostate cancer cells. Using reverse transcriptase polymerase chain reaction, we observed that AR signaling was disrupted by mahanine treatment, leading to a prominent decline in the expression of a number of AR target genes. Androgen response element-luciferase and PSA promoter-luciferase assays showed that androgen-induced AR transcriptional activity diminished by approximately 85% upon mahanine treatment. Furthermore, mahanine induced the export of the AR from the nucleus, resulting in its accumulation in the cytoplasm. Cellular levels of the AR were found to decrease in a time- and dose-dependent manner following mahanine treatment, without any noticeable change in its message levels, suggesting that mahanine affected AR protein levels post-translationally, without any effect on its gene expression. Concomitant administration of a proteasome inhibitor, MG132, significantly rescued the decline in AR levels observed upon mahanine treatment, indicating that mahanine induced proteasomal degradation of the AR. Collectively, these data demonstrate that mahanine treatment disrupts AR signaling in prostate cancer cells, leading to its cytoplasmic accumulation and subsequent degradation by proteasomal mechanisms, and suggest a potential therapeutic role for mahanine in prostate cancer treatment. This work is supported by NIH R01 CA131123. Citation Format: Karishma Amin, Shankar Jagadeesh, Nabin Barua, Samir Bhattacharya, Partha P. Banerjee. A novel natural product disrupts androgen receptor signaling in prostate cancer cells. [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 3238. doi:10.1158/1538-7445.AM2013-3238
S77 Prone Positioning and Intravenous Steroids For the Management of Severe ARDS
Authors: L Gupta, Ben SiuJames
Journal: Thorax (2012)

<h3>Introduction</h3> Prone positioning and intravenous steroids represents a treatment option in patients with severe ARDS because most of the clinical manifestations in ARDS is secondary to excess fluid in the interstitium and alveoli and presence of inflammatory cells in the fluid. <h3>Objective</h3> To assess the impact of prone positioning and steroids in severe ARDS and to assess and identify prognostic factors and potential predictors of mortality in ARDS patients. <h3>Methods</h3> This is a retrospective study of 46 patients with severe ARDS from 2009–2011. The patient charts were reviewed and the impact of prone positioning and steroids was observed on severe ARDS patients. The primary outcome measured were ICU length of stay, number of ventilator days and 30 day mortality. Various prognostic factors such as history of diabetes, alcoholism, and presence of hypo-albuminemia, coagulopathy, sepsis and lactic acidosis were taken into account. Calculations were made in regards to the Lung Injury Predictive Score (LIPS) as determined by Chest Roentgenogram score, Hypoxemia Score, PEEP Score and Compliance score. The LIPS score was calculated for projecting the severity of ARDS. The use of statins on various outcome measures was also observed. <h3>Results</h3> A total of 46 patients were treated in the ICU for ARDS. The number of ventilator days averaged from 5–35 days. The incidence of predisposing conditions as well as risk modifiers was correlated with the LIPS score. All of these patients were on ARDS net protocol and received intravenous antibiotics. Statistical analysis revealed a favourable impact of prone positioning with steroids on the mortality, duration of ICU stay and ventilator days. A significant difference in the LIPS score was noted in patients receiving IV steroids and prone positioning on day 2. Use of statins also influenced the duration of ICU stay and a significant impact on the mortality of this cohort of patients. <h3>Conclusions</h3> Prone positioning is an effective adjunct intervention in conjunction with intravenous steroids for treating severe ARDS. It is a valid option for patients with refractory ARDS to conventional treatment. More studies need to be done to validate the impact of statins on different outcome measures in the ICU.
P328 ROLE OF MYCOPHENOLATE MOFETIL (MMF) IN STEROID NON RESPONSIVE SEVERE ACUTE ALCOHOLIC HEPATITIS: A RANDOMIZED OPEN LABEL PLACEBO CONTROL PROSPECTIVE CLINICAL PILOT TRIAL – MASH TRIAL
Authors: P.P. Basu, M. Aloysius, N.J. Shah, R.S. Brown
Journal: Journal of Hepatology (2014)
Insulin pumps improve control and reduce complications in children with type 1 diabetes
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Children with type 1 diabetes who use an insulin pump rather than injections have better long term control of their disease and experience fewer episodes of severe hypoglycaemia and diabetic ketoacidosis, a study has found.

Previous studies have shown that insulin pumps improve HbA1c, although some found this was only temporary. Reductions in severe hypoglycaemia have also been demonstrated. 

Few of these studies have lasted more than a few years, so to assess the impact of insulin pumps in children longer term, researchers from the Princess Margaret Hospital for Children in Perth, Australia, set up the population based study for a seven year period.

They recruited 345 children on insulin pump therapy who were matched to controls …
THU0188 Can Baseline Levels of Autoantibodies Predict SDAI Remission in Patients with Established Rheumatoid Arthritis Treated with TNF Inhibitors?
Authors: C. Pomirleanu, R. Chirieac, C. Ancuta
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> It remains still unclear whether autoantibodies are useful biomarkers to tailor the choice of biological treatment in rheumatoid arthritis (RA). <h3>Objectives</h3> The main aim of our study was to identify predictive factors for response to TNF inhibitors in patients with established RA with a special focus on baseline levels of autoantibodies. <h3>Methods</h3> We performed a prospective observational 12 months study in 90 consecutive active established RA receiving their first anti-TNF agent: adalimumab (33), etanercept (30), infliximab (27). Standard assessments consisted of 28-joint counts, patient reported outcomes, inflammatory tests and activity scores (DAS28-ESR, SDAI) performed every three months, while total and IgA-RF and ACPA every six months. The primary outcome measure was SDAI remission (≤ 3.3). Univariate and multivariate logistic regression models were used to estimate the association between baseline variables and SDAI remission at 12 months, using SPSS-16 software, p&lt;0.05. <h3>Results</h3> 39.7% of RA achieved SDAI remission after 12 months of anti-TNFs. Baseline levels of autoantibodies in subgroup analysis were 182.3IU/ml for total RF, 14.4IU/ml for IgA-RF and 75.7 IU/ml for ACPA, respectively. Statistically significant moderate correlation between SDAI remission and baseline IgA-RF (Spearman: r=0.321, p=0.002), as well as weak correlation with ACPA (Sperman: r=0.194, p=0.047) were reported, while no correlation with total initial RF levels (Sperman: r=0.021, p=0.844). Furthermore, patients with baseline levels of total RF ≤100IU/ml (OR 1.09; IC95% 0.45-2.61), ACPA ≤40IU/ml(OR 1.99; IC95% 0.95-4.17) and IgA-RF ≤20IU/ml(OR 5.76; IC95% 1.43-23.23) were more likely to achieve SDAI remission. <h3>Conclusions</h3> The presence as well as the titer of IgA-RF isotype and ACPA before starting anti-TNFα therapy were significantly correlated with SDAI remission at 12 months. However, this correlation is not strong enough to allow a reliable prediction in individual patients. <h3>Disclosure of Interest</h3> None Declared
Abstract 1411: Overexpression of IFITM1 is associated with gastric cancer and its silencing inhibits migratory and invasive potential of tumor cells
Authors: Jieun Lee, Naaleum Song, Sung-Ho Goh, Il Ju Choi, Jin Sook Jeong, Yeon-Su Lee
Journal: Cancer Research (2011)

Abstract Gastric cancer is the most common types of human cancer with an annual incidence of approximately 870,000 new cases worldwide (Crew K D, Neugut A I, Epidemiology of gastric cancer, World J Gastroenterol 2006;12(3):354-362). Despite its high prevalence, the risk factors and tumorigenesis of gastric cancer are not clearly identified. Consequently, the identification of the oncogene or tumour suppressor gene in gastric cancer has been the focus of many researches. In our effort to find gastric cancer related genes, we analysed the gene expression profiles in 30 pairs of gastric cancer patient samples (tumour and normal tissue) using microarrays and identified interferon-induced transmembrane protein 1 (IFITM1) as a highly up-regulated gene in tumor tissues. IFITM1, also known as 9-27 or Leu13, is a cell surface molecule and the IFN-inducible transmembrane protein family. However, there have been a few papers of IFITM1 explaining its function, and the role of IFITM1 in cancer is poorly understood. In the present study, we examined the roles of IFITM1 for gastric cancer and its function for tumoringenesis. Quantitative real-time PCR, western blot analysis and immunohistochemical staining were performed to confirm the cancer specific expression pattern of IFITM1. In various gastric cancer cell lines, IFITM1 mRNA expression level was highly up-regulated in comparison human mammary epithelial cell (HMEC). Furthermore, mRNA expression of IFITM1 was significantly up-regulated in cancer tissues than matching normal tissues. In addition, IFITM1 overexpression was observed in gastric adenocarcinoma by immunohistochemistry. Interestingly, cells which overexpressed IFITM1 exhibit an increased migration, invasion and wound healing potential. Consistently, IFITM1 knockdown cells by siRNA showed a decreased invasiveness. Our findings suggest that IFITM1 plays an important role for the migration, invasion and wound healing capacity of cancer cells and associated with progression of gastric cancer. 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 1411. doi:10.1158/1538-7445.AM2011-1411
Improving Adherence — Money Isn't the Only Thing
Authors: Lee Goldman, Arnold M. Epstein
Journal: New England Journal of Medicine (2011)

Interventions that both improve outcomes and save costs are unusual, but the provision of lifesaving medications to survivors of myocardial infarction is one such example.1 In the past, physicians' poor compliance with evidence-based guidelines was a major reason for suboptimal use of such medications. Now, with help from the dissemination of quality metrics, cost-saving medications such as beta-blockers, aspirin, and angiotensin-converting–enzyme (ACE) inhibitors are nearly universally prescribed to eligible patients after myocardial infarction,2,3 so the focus has switched from physician prescribing to patient adherence. The concept of value-based insurance design,4 which is encouraged by the Patient Protection and Affordable . . .
Abstract 2225: GSK3β plays a significant role in Ras driven tumors potentially through an upstream effect on AKT
Authors: Raeshell S. Sweeting, Hong J. Kim, Albert S. Baldwin
Journal: Cancer Research (2012)

Abstract Pancreatic cancer is a highly aggressive cancer that is resistant to most drug therapies. Lung cancer is the number one cause of cancer deaths in the US and worldwide. Both of these tumors are known to have high levels of Ras oncogenic mutations (50 and 90% respectively). AKT is known to phosphorylate and inactive Glycogen Synthase Kinase 3 (GSK3). Additionally, GSK3 has been shown to play a role in oncogenesis in pancreatic cancer and lung cancer. Given the high level of AKT activity in transformed cells these two processes would appear to be at odds. However, much of the work on GSK3 has focused on the beta subunit. We have found that the alpha subunit plays a role in tumor proliferation and AKT activity. We see a significant effect of knockdown of GSK3β in Ras transformed pancreatic (Panc1, MiaPaca) and lung cancer (A549) cell lines in proliferation assays, with an approximately 70% decrease in growth compared to siControl cells. In contrast, the knockdown of the GSK3β subunit resulted in no decrease in cell proliferation in A549 cells compared to a 45% decrease in Panc 1 cells. Additionally, knockdown of GSK3β resulted in decreased levels of AKT activity by Western blot analysis as compared to siControl and GSK3β. Previous studies have focused on the role of the beta subunit of GSK3 in oncogenesis. Additionally, AKT has been studied as an upstream regulator rather than a downsteam target of GSK3. Our early studies suggest that the GSK3β subunit may play a significant role in the growth of Ras driven tumors cell lines upstream of AKT, and should be a potential target for therapeutic strategies. 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 2225. doi:1538-7445.AM2012-2225