tbuckley/cabot-search huggingface dataset:
Abstract 726: Copy number amplification of the PIK3CA gene is associated with poor prognosis in early-stage head and neck squamous cell carcinoma
Authors: Toshihito Suda, Takanori Hama, Mitsuyoshi Urashima, Takakuni Kato, Hiroshi Moriyama
Journal: Cancer Research (2012)

Abstract Background: Deregulation of the EGFR signaling pathway is one of the most frequently observed genetic abnormalities that drive cancer development. Mutations in downstream components of the EGFR signaling pathway, including KRAS, BRAF and PIK3CA, have been reported in numerous cancers. However, extensive mutation analysis of these genes in clinical samples has not been performed for head and neck squamous cell carcinoma (HNSCC). Patient and methods: We examined mutations and copy number alterations of KRAS, BRAF and PIK3CA in 115 clinical specimens of HNSCC obtained from surgically treated patients. Results: We identified three mutations in K-RAS and two mutations in PIK3CA. Copy number amplification was found in 42 cases (36.4%) for PIK3CA, 12 cases (10.4%) for K-RAS and nine cases (7.8%) for BRAF. Tumor recurrence and death occurred in 49 (42.6%) and in 22 (19.3 %) patients during the median follow-up of 723 days, respectively. Kaplan-Meier survival analysis revealed that in patients with early-stage carcinoma (Stages I-III), copy-number amplification of PIK3CA was drastically associated with cancer relapse. Conclusion: Copy number amplification of the PIK3CA is associated with poor prognosis in early-stage HNSCC. The PIK3CA copy number status will serve as a marker of poor prognosis in patients with HNSCC. 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 726. doi:1538-7445.AM2012-726
An African American man with dysphagia: a unique initial presentation of sarcoidosis
Authors: J. Samarasena, E. Chu, V. Muthusamy
Journal: Endoscopy (2012)

A 46-year-old African American man whose past medical history was only notable for hypertension was referred to the gastrointestinal clinic with a 1-year history of dysphagia. The dysphagia related only to solid foods and had been progressively worsening over the preceding few months. The patient described the sensation of food getting stuck at the level of the mid to lower chest. He denied any odynophagia or difficulty with swallowing liquids. He denied any chronic heartburn symptoms, regurgitation, hematemesis, or weight loss. Physical examination was unremarkable. Laboratory studies including complete blood count, basic metabolic panel, and liver function tests were within normal limits. A barium swallow was performed and revealed a mid-esophageal stricture with obstruction of approximately 50 % of the lumen.
Abstract 426: The molecular microenvironment critically affects the formation of isoDGR-dependent integrin binding sites in fibronectin
Authors: Flavio Curnis, Angela Sacchi, Renato Longhi, Angelo Corti
Journal: Cancer Research (2011)

Abstract Fibronectin (FN) is an adhesive protein present in most body fluids and in the extracellular matrix of many tissues. This protein mediates a variety of cellular interactions with extracellular matrix and play important roles in haemostasis, thrombosis, inflammation, wound repair and angiogenesis. FN is constituted of three types of repeating homologous modules termed FN-I, FN-II and FN-III. Each module contains binding sites for molecules of the extracellular matrix and for cell adhesion receptors, such as integrins. Moreover, FN contains four NGR sites located in the: 5th type I, 2nd type II, 7th type I repeat, 9th type III repeats. We have previously shown that the NGR site of the 5th type I repeat (FN-I5) rapidly undergoes deamidation leading to formation of isoDGR. A deamidated FN fragment corresponding to this domain binds αvβ3, inhibits endothelial cell adhesion and proliferation and inhibits tumor growth in animal models. In the present study we have investigated the molecular mechanisms that regulate isoDGR formation in FN in vivo. We provide evidence to suggest that FN purified from plasma contains very low amounts of isoDGR (&amp;lt;3%) despite its long half life (48h). In contrast, using anti-isoDGR antibodies, we observed that isoDGR is formed in significant amounts in small FN fragments injected in mice and left to circulate for 4 or 6 h (&amp;gt;17% in 4 h). In vitro cell adhesion assays, antibody binding assays and integrin binding studies showed that FN deamidation can rapidly occur when FN is bound to microtiter plates, a condition known to cause conformational changes in this protein, but not with FN in solution. Rapid deamidation was observed to occur also with short fragments (FN-I5), either adsorbed on microtiter plates or in solution. These results suggest that the kinetics of NGR-to-isoDGR transition in plasma FN is slower than its clearance rate. Furthermore, the finding that conformational changes and/or protein fragmentation increase the kinetics of NGR-to-isoDGR transition suggest that changes in the molecular microenvironment of NGR sites, potentially occurring after FN deposition in tissues, could be critical for the formation of isoDGR integrin binding sites. 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 426. doi:10.1158/1538-7445.AM2011-426
250 RELATIONSHIP BETWEEN PLASMA CONCENTRATION AND DAILY DOSE OF SORAFENIB IN CIRRHOTIC PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC)
Authors: M. Bazzica, C. Fucile, F. Mattioli, S. Marenco, F. Lantieri, V. Savarino, A. Picciotto
Journal: Journal of Hepatology (2013)
AB0849-HPR Patients’ perceptions and experiences related to intensive combination treatment strategies for early rheumatoid arthritis: a qualitative study
Authors: S. Meyfroidt, K. Van der Elst, D. De Cock, L. van Hulst, J. Joly, M. Hulscher, R. Westhovens, P. Verschueren
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In the current recommendations for early rheumatoid arthritis (RA) management, the focus is set to achieve clinical remission as soon as possible with an early and intensive treatment. Our previous research indicated that rheumatologists' perception of patients' concerns at initation influenced their prescription behaviour of intensive combination treatment strategies (ICTS). Understanding patients' perspectives on ICTS is necessary to identify opportunities to improve early RA care. <h3>Objectives</h3> To explore early RA patients' perceptions of and experiences with ICTS at an early stage in their care process. <h3>Methods</h3> A qualitative study was carried out using individual semi-structured interviews with early RA patients who agreed to ICTS within the CareRA trial four months earlier. The CareRA trial is a multicentre RCT across Flanders comparing different ICTS for early RA with conventional DMARDs plus step-down glucocorticoids. Data saturation was reached after 26 interviews. Each interview was recorded, transcribed literally and thematically coded using the constant comparative method. <h3>Results</h3> Patients indicated that when ICTS was advised they were afraid of the side-effects in the short term and of the health consequences of the treatment in the long-term. At the same time, many patients reported that it was confronting to hear what the treatment entailed just after being burdened with the diagnosis of RA. Motivations for the decision to agree with intensive treatment initiation were faith in the treatment and healthcare team and knowing the medication would be phased out eventually. Patients who initiated ICTS reported that their negative feelings disappeared and that ICTS was easily incorporated into their daily life. <h3>Conclusions</h3> Despite their concerns when ICTS was advised, most patients had positive experiences with ICTS once initiated. The study findings may be helpful for healthcare professionals to understand patients' concerns and to support them in their decision-making process to initiate ICTS. <h3>References</h3> Meyfroidt S, van Hulst L, De Cock D, Van der Elst K, Joly J, Westhovens R, Hulscher M, and Verschueren P. (2012) Intensive combination treatment strategies for early rheumatoid arthritis: a qualitative study of rheumatologists' and nurses' experiences and views. Manuscript submitted for publication. <h3>Acknowledgements</h3> The authors thank the healthcare professionals and their patients for their participation in this study. <h3>Disclosure of Interest</h3> None Declared
Introduction of value based pricing may miss its 2014 target, NICE says
Authors: N. Hawkes
Journal: BMJ (2013)

With a new chairman, a new name, and a new role the National Institute for Health and Care Excellence enters the world of the changed NHS in England with only its acronym unchanged (NICE).

Although its writ now extends to social care as well as healthcare, it has ingeniously recast its name so that the well established NICE brand can be retained. Yesterday (2 April) it published its first two pieces of social care guidance, which cover supporting people with dementia and quality standards for the health and wellbeing of children and teenagers in care.1 2

Under the Health and Social Care Act NICE has become a statutory body rather than a strategic health authority that was at the whim of ministers. “As an SHA we could be written in or out by a health secretary on a daily basis,” said Andrew Dillon, who remains chief executive. “Now …
Abstract 3380: Overcoming platinum resistance in ovarian cancer using the novel compound MLN4924.
Authors: Amir A. Jazaeri, Etsuko Shibata, Jonghoon Park, Jennifer Bryant, Mark R. Conaway, Susan C. Modesitt, Peter G. Smith, Michael Milhollen, Allison J. Berger, Anindya Dutta
Journal: Cancer Research (2013)

Abstract Purpose: The objective of this investigation was to evaluate the preclinical activity of MLN4924, an investigational inhibitor of the NEDD8-activating enzyme, against chemoresistant and chemosensitive ovarian cancer cells. ExperimentalDesign: Efficacy of MLN4924 both alone and in combination with cisplatin was assessed using short-term tetrazolium based and longer term focus formation assays. Mechanistic studies included cell cycle analysis, evaluation of DNA-platinum adduct formation (using an ELISA), and evaluation of DNA damage repair pathways. In addition, we employed an siRNA screen to assess the contribution of each member of the Cullin RING-Ligase (CRL) family of E3 ubiquitin ligases, the best characterized downstream mediators of MLN4924’s biological effects. Results: Single agent MLN4924 exhibited moderate activity in ovarian cancer cell lines. The combination of MLN4924 with cisplatin or carboplatin resulted in significant platinum sensitization in SKOV3 and ES2 cells, as well as, in several primary ovarian cancer cell lines established from high grade serous, clear cell, and serous borderline ovarian tumors. Furthermore, the platinum sensitizing effect of MLN4924 was also observed in several in vitro models of platinum resistant ovarian cancer (using both established and primary chemoresistant ovarian cancer cells). Mechanistically, we show that depletion of CUL3 and CUL5 augment, while knockdown of CUL1 and CUL4A antagonize cisplatin-induced cytotoxicity in ovarian cancer cells. The combination of cisplatin and MLN4924 was not associated with DNA re-replication, altered platinum-DNA adduct formation, or abrogation of FANCD2 monoubiquitination. Conclusions: Our investigation reveals a novel mechanism for overcoming platinum resistance in vitro, and provides a strong rationale for clinical investigations of platinum and MLN4924 combinations in ovarian cancer. This work also highlights that different CRL ubiquitination pathways can have distinct and opposing effects on platinum sensitivity and resistance in ovarian cancer cells. Citation Format: Amir A. Jazaeri, Etsuko Shibata, Jonghoon Park, Jennifer Bryant, Mark R. Conaway, Susan C. Modesitt, Peter G. Smith, Michael Milhollen, Allison J. Berger, Anindya Dutta. Overcoming platinum resistance in ovarian cancer using the novel compound MLN4924. [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 3380. doi:10.1158/1538-7445.AM2013-3380
Gene Therapy for Lung Cancer Still On Hold
Authors: Susan Jenks
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Gene Therapy for Lung Cancer Still On Hold Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 7, 6 April 1994, Page 486, https://doi.org/10.1093/jnci/86.7.486 Published: 06 April 1994
THU0409 Leucine-Rich Alpha2-Glycoprotein is A Useful Biomarker for Monitoring of Disease Activity in Patients with Adult-Onset Still's Disease
Authors: Y.-J. Ha, E.-J. Kang, S.-W. Lee, Y.-B. Park, S.-K. Lee, J.-S. Song, S.T. Choi
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Leucine-rich alpha2-glycoprotein (LRG) is a protein which contains leucine-rich repeats. Though physiologic functions of LRG have not been clearly defined, its expression was up-regulated during neutrophil differentiation and its levels were significantly elevated in some chronic inflammatory diseases such as inflammatory bowel disease. <h3>Objectives</h3> Our study aimed to investigate whether serum leucine-rich α2-glycoprotein (LRG) levels are elevated in patients with adult-onset Still9s disease (AOSD) and determine their correlation with disease activity parameters. <h3>Methods</h3> We enrolled 39 patients with AOSD, 39 patients with rheumatoid arthritis (RA), and 39 controls. Forty-five serum samples from the patients with AOSD were assayed for LRG using enzyme-linked immunosorbent assay. Comprehensive AOSD activity was determined by modified Pouchot score. <h3>Results</h3> Serum LRG levels were significantly elevated in patients with AOSD (128.8±40.8 ng/mL) compared to those in patients with RA and in controls (35.9±15.7 ng/mL, <i>p</i> &lt;0.001; 22.4±6.1 ng/mL, <i>p</i> &lt;0.001, respectively). Patients with active AOSD had a significantly higher LRG level than those with inactive disease (141.4±31.3 ng/mL vs 79.8±37.1 ng/mL, <i>p</i> =0.002). Serum LRG levels were positively correlated with C-reactive protein (γ =0.387, <i>p</i> =0.015), lactate dehydrogenase (γ =0.370, <i>p</i> =0.026), and ferritin (γ =0.687, <i>p</i> &lt;0.001) levels, and the modified Pouchot score (γ =0.756, <i>p</i> &lt;0.001). Serum LRG levels decreased significantly after treatment in all 6 patients with active AOSD who had follow-up evaluations (<i>p</i> =0.007). The best cutoff value for LRG to distinguish AOSD from RA was 67.9 ng/mL, with a sensitivity of 92.3% and a specificity of 97.4%. <h3>Conclusions</h3> Serum LRG levels were increased in patients with AOSD and were well-correlated with disease activity measures. LRG may be a useful biomarker for distinguishing AOSD from RA and monitoring the disease activity of AOSD. <h3>References</h3> Takahashi N, Takahashi Y, Putnam FW. Periodicity of leucine and tandem repetition of a 24-amino acid segment in the primary structure of leucine-rich alpha 2-glycoprotein of human serum. Proc Natl Acad Sci U S A 1985;82:1906-10. Serada S, Fujimoto M, Terabe F, Iijima H, Shinzaki S, Matsuzaki S, et al. Serum leucine-rich alpha-2 glycoprotein is a disease activity biomarker in ulcerative colitis. Inflamm Bowel Dis 2012;18:2169-79. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2855
BMET-14STAT3 INHIBITION ENHANCES THERAPEUTIC EFFICACY OF RADIATION TREATMENT AGAINST ESTABLISHED BRAIN METASTASIS IN MURINE MELANOMA MODEL
Authors: Yuuri Hashimoto, Nasser K. Yaghi, Jun Wei, Neal Huang, Ravesanker Ezhilarasan, Ling-Yuan Kong, Shouhao Zhou, Padmanabh Chivukula, David C. Webb, Waldemar Priebe, Joseph E. Payne, Erik P. Sulman, Amy B. Heimberger
Journal: Neuro-Oncology (2015)

INTRODUCTION: Melanoma patients that develop brain metastasis have a median survival of 6 months. Radiation, a standard of care for local control of melanoma, has been reported to have immune stimulatory capacities. Therefore, we investigated the combinatorial effect of inhibitors of the signal transducer and activator of transcript 3 (STAT3) pathway, a potent mediator of immune suppression, and whole-brain radiation in a murine brain metastasis model. METHODS: C57BL/6 mice were intracerebrally implanted with B16 melanoma, irradiated with 7.5 Gy, and treated with an advanced lipid nanoparticle system that contained miR-124 (LNP-124) that inhibits the STAT3 pathway, or WP1066, a small molecule inhibitor of STAT3. Mice surviving 130+ days after tumor implantation were subcutaneously rechallenged with tumor. RESULTS: Monotherapy (LNP-124, WP1066, or radiation alone) demonstrated longer survival relative to untreated control mice; combination therapies further extended survival compared to single treatment agents. Median survival for mice receiving radiation combined with LNP124 or WP1066 was 65 days and 45.5 days, respectively, compared to 15 days for untreated mice and 19 - 40 days for monotherapy. While no untreated mice (control) survived over 20 days, the survival rate at day 130 for mice receiving combination therapy was almost 40%. Flow cytometry analysis showed higher IL-2 production in T cells from tumor-draining lymph nodes in mice treated with radiation plus STAT3 inhibitor. SUMMARY: These results indicate the combination of STAT3 inhibition and radiation enhances the therapeutic effect against established murine brain metastasis. The implications for this combination on antitumor immunity, immunologic memory and protection from recurrence will also be discussed.
AB1021 2012 update of the french guidelines for the pharmacological treatment of postmenopausal osteoporosis
Authors: K. Briot, B. Cortet, T. Thomas, P. Guggenbuhl, C. Roux
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To update the evidence-based position statement published by the French National Authority for Health (HAS) in 2006 regarding the treatment of postmenopausal osteoporosis under the auspices of the French Society for Rheumatology and the GRIO (Groupe de Recherche et d’Information sur les Ostéoporoses), and with the participation of several Societies (Collège National des Gynécologues et Obstétriciens Français, Groupe d’Etude de la Ménopause et du Vieillissement hormonal, Société Française de Chirurgie Orthopédique, Société Française d’Endocrinologie, Société Française de Gériatrie et de Gérontologie). <h3>Methods</h3> a panel of multidisciplinary clinician experts in the bone field was enlisted to reach consensus on recommendations. The present manuscript is based on a systematic review and a critical appraisal of the currently available literature according to methodology used by the HAS. <h3>Results</h3> –The updated recommendations target women with low trauma fracture defined as severe who require an anti-osteoporotic treatment regardless of the age. In these cases; all the treatments could be considered; zoledronic acid should be used as a first line therapy after hip fracture –In the other situations (absence of fracture and non-severe fracture) the indication of a treatment depends on the BMD and the FRAX® values. All registered treatments can be used, raloxifen and ibandronate use should be limited to women with low peripheral risk fracture –The treatment will be prescribed for a first sequence of 5 years; its continuation or not depends on the 5-year evaluation results. <h3>Conclusions</h3> these updated recommendations propose a clarification of the pharmacological management of postmenopausal osteoporosis for all practitioners. <h3>Disclosure of Interest</h3> K. Briot Grant/Research support from: Lilly, Consultant for: Amgen, Lilly, MSD, Novartis, B. Cortet Grant/Research support from: Amgen, Lilly, MSD, Novartis, Roche, Consultant for: Amgen, Daiichi-Sankyo, Ferring, GSK, Lilly, MSD, Medtronic, Novartis, Servier, T. Thomas Grant/Research support from: Amgen, Chugaï, Merck, Novartis, Pfizer, Roche, Servier, UCB, Warner-Chilcott, Consultant for: Amgen, Genévrier, GSK, Lilly, Merck, Novartis, Servier, P. Guggenbuhl Grant/Research support from: Lilly, Roche, Consultant for: Amgen, Dai-ichi Sankyo, Lilly, MSD, Novartis,Roche, Servier, C. Roux Grant/Research support from: Bongrain, Amgen, Lilly, MSD, Servier, Consultant for: Amgen, Lilly, MSD, Roche, Novartis, Servier
THE INTERACTION OF THE CARDIOVASCULAR RISK FROM THE NEW ACC/AHA POOLED COHORT EQUATIONS RISK ESTIMATOR AND CARDIORESPIRATORY FITNESS: THE HENRY FORD EXERCISE TESTING PROJECT (THE FIT PROJECT)
Authors: Mouaz H. Al-Mallah, Stephen Juraschek, Clinton Brawner, Steven Keteyian, Zeina A. Dardari, Michael Blaha
Journal: Journal of the American College of Cardiology (2015)
Effects of the Interaction of Dietary Fat and Protein on &lt;italic&gt;N&lt;/italic&gt;-Nitrosobis(2-oxopropyl)amine-Induced Carcinogenesis and Spontaneous Lesions in Syrian Golden Hamsters&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D F Birt, P M Pour
Journal: JNCI Journal of the National Cancer Institute (1985)

Syrian golden hamsters were fed four diets in experiments designed to evaluate the effects of the interaction of dietary fat and protein on carcinogenesis induced by N-nitrosobis(2-oxopropyl)amine [(BOP) CAS: 60599-38-4]. The diets consisted of two levels of dietary fat [4.5 g (low fat, LF) or 18 g (high fat, HF) of corn oil/385 kilocalories (kcal)]. These levels were fed with each of two levels of dietary protein [9 g low-protein (LP) and 36 g high-protein (HP) casein/385 kcal]. The four diets were fed to two separate groups of hamsters at two different periods in their life-span. For testing of the effects of diet on tumor initiation, one group received the diets from 3 to 7 weeks of age. At 8 weeks, they were given injections sc of 10 mg BOP/kg body weight and placed on a control diet [9 g corn oil (medium fat) and 18 g casein (medium protein)/385 kcal]. The other group received control diet until 8 weeks of age, at which time they were given injections of BOP and placed on the four diets. This group was designed to test the effects of the diets on tumor development. BOP-induced lesions in the lungs, liver, common bile duct, gallbladder, and kidneys are described; results in the pancreas were reported separately. In hamsters fed the four diets after BOP treatment, the LF-LP groups had the fewest tumors, the LF-HP-fed and HF-LP-fed groups had intermediate yields of tumors, and the hamsters given HF-HP diet exhibited the largest numbers of neoplasms. Several specific tumor types showed a similar pattern. For example, the pulmonary adenoma incidence, which was low in the non-BOP-treated hamsters, was higher in the HF-HP group than in those fed LF-HP diet after BOP, but it was not influenced by fat at the LP level. In addition, renal adenomas were observed at a low incidence in non-BOP-treated hamsters and in hamsters fed LF-LP levels before or after BOP treatment (0.5% incidence) but were present at an 8% incidence in all other BOP-treated groups. The incidence of biliary cystic adenomas was highest in male hamsters that received HF diets, irrespective of BOP treatment, and BOP treatment resulted in increased yields of this lesion in females only in groups given HF-LP diet.(ABSTRACT TRUNCATED AT 400 WORDS)