tbuckley/cabot-search huggingface dataset:
Case 31-2013
Authors: Howard M. Heller, Carol C. Wu, Virginia M. Pierce, Richard L. Kradin
Journal: New England Journal of Medicine (2013)

A 29-year-old man was seen in an outpatient clinic because of abdominal pain, fever, and weight loss. Testing for HIV antibodies was positive, and the CD4 T-lymphocyte count was 10 per cubic millimeter. Chest imaging revealed tiny nodules in both lungs.
Abstract IA1: Building molecules to guide anticancer therapy
Authors: Emilia S. Olson, Roger Y. Tsien, Elamprakash N. Savariar, Jessica L. Crisp, Tao Jiang, Todd A. Aguilera, Mike A. Whitney, Paul Steinbach, Lesley G. Ellies, Quyen T. Nguyen
Journal: Cancer Research (2011)

Abstract For clinical imaging, we need synthetic molecules with novel amplifying mechanisms for homing to diseased tissues. Activatable cell penetrating peptides (ACPPs) are polycationic cell penetrating peptides (CPPs) whose cellular uptake is minimized by a polyanionic inhibitory domain and then restored upon proteolysis of the peptide linker connecting the polyanionic and polycationic domains. Local activity of proteases able to cut the linker causes amplified retention in tissues and uptake into cells. ACPPs on dendrimers labeled with Cy5 and Gd-DOTA enable whole body magnetic resonance imaging (Olson et al (2010) PNAS 107: 4311–4316) followed by fluorescenceguided surgery. Such fluorescence guidance improves tumor-free survival in two animal models (Nguyen et al (2010) PNAS 107: 4317–4322). Contrast for tumor over normal tissues is amplified and accelerated when the polyanionic domain includes an acceptor of fluorescence resonance energy transfer (FRET), because loss of FRET (monitored either by multispectral emission or donor excited-state lifetime) instantly signals proteolysis without waiting for uncleaved substrate to wash out of normal tissues. Thrombin-cleavable ACPPs accumulate in atherosclerotic plaques, and their labeling intensity seems to correlate with progression towards rupture. Separately, we have developed fluorescent peptides that light up peripheral nerves to show surgeons where not to cut (Whitney et al (2011) Nature Biotech. 29: 352–356). Thus we believe that basic tumor biology and molecular design can help improve early detection and surgical resection, not just chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr IA1.
Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor
Authors: Alastair J.J. Wood, Graham J. Lieschke, Antony W. Burgess
Journal: New England Journal of Medicine (1992)

FOUR colony-stimulating factors influence the survival, proliferation, differentiation, and functional activation of myeloid hematopoietic cells: macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor (G-CSF), granulocytemacrophage colony-stimulating factor (GM-CSF), and interleukin-3 (formerly known as multi-colony-stimulating factor).1 2 3 Various other cytokines and factors are also implicated in these processes, including interleukins 1, 5, 6, and 11 and the recently identified Steel factor (variously designated c-kit ligand, mast-cell growth factor, and stem-cell factor).4 , 5 Of these factors, only G-CSF and GM-CSF are commercially available for clinical use. G-CSF has been approved in the United States and major European countries for the reduction of infection after . . .
Abstract A63: TLR5 agonist CBLB502 protects mice from Fas-mediated liver damage without protecting tumors
Authors: Lyudmila Burdelya, Katerina Leonova, Bojidar Kojouharov, Jean Veith, Semra Aygun-Sunar, Ilya Gitlin, Shyam Allamaneni, Anatoli Gleiberman, Andrei Gudkov
Journal: Cancer Research (2011)

Abstract We have previously shown the strong radioprotective properties of the Toll-like receptor 5 (TLR5) agonist flagellin and its derivative CBLB502 in both mouse and non-human primate models (Burdelya et al., 2008, Science 320: 226–230). Because no protection has been observed in any in vitro cell model regardless of the TLR5 status of the cells, we hypothesized that the radioprotective effects of the TLR5 agonist are indirect and mediated by factors produced by primary cells responding to flagellin in the organism. Using a combination of tools, including NF-kB-responsive reporter mice and immunohistochemical determination of tissues responding to CBLB502 by NF-kB activation, we defined liver hepatocytes as the primary pharmacological targets of flagellin. Surgical exclusion of the liver from the blood circulation completely abolished radioprotection of the bone marrow hematopoietic progenitor cells by CBLB502 suggesting that the liver acts as a mediator of at least some of the effects of the TLR5 agonist. Since the induction of NF-kB is known to activate multiple pro-survival mechanisms, we further hypothesized that administration of the TLR5 agonist can result in liver resistance to otherwise toxic conditions. Mice treated with Fas agonistic antibodies were employed as a model of acute hepatotoxicity. Injection of CBLB502 showed a strong preventive effect against Fas-mediated injury rescuing all of the injected mice in contrast to complete lethality in the control groups. The ability of CBLB502 to protect the liver was also demonstrated via reduced levels of liver enzymes in the peripheral blood and caspase activation in liver extracts of mice treated with Fas agonistic antibodies. Using two syngeneic tumor models, colon adenocarcinoma CT26 and lymphoma A20, growing as liver metastases in mice, we found that CBLB502 injections not only prevented liver damage, but also suppressed tumor appearance and growth when injected with or without anti-Fas antibodies. Thus, TLR5 agonist has potential to become a new agent for liver protection and suppression of liver metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A63.
Abstract B03: Cisplatin-resistant cells possess collateral sensitivity to folate antimetabolites
Authors: Shih-Shin Chang, Hirohito Yamaguchi, Mien-Chie Hung
Journal: Clinical Cancer Research (2015)

Abstract Cisplatin is widely used as a first-line chemotherapeutic agent for lung cancers. Although effective initially, lung cancer cells eventually acquire resistance to cisplatin, causing tumor recurrence. Understanding mechanisms that govern cisplatin resistance is expected to improve therapeutic efficacy in lung cancer patients. Although various studies using cisplatin-resistant cell lines have revealed possible mechanisms of resistance, the applicability of these mechanisms in a clinical setting are debatable. One possible reason for this discrepancy may be the use of cell line models which are exposed to unnaturally high doses of cisplatin to yield cells with a resistant phenotype. These cell lines may not be representative of naturally arising cisplatin-resistant cells in tumors that are treated according to a clinically established dose and schedule. Therefore, to improve the experimental model, we have established two new cisplatin-resistant lung cancer cell lines through intermittent low dose challenges that mimic a clinical treatment schedule (one pulse/month for up to six cycles). The resistant cell lines resulting from this procedure demonstrate improved clonogenic potential and sphere-forming properties, suggesting an increase in the population of tumor-initiating cells. Interestingly, via testing with several different anti-cancer drugs, we found that these resistant cells are more sensitive to the antifolate Pemetrexed, in comparison to their parental cells. To conclude, our study suggests that sequential administration of antifolates might be useful in the treatment of lung cancers that have acquired cisplatin resistance. Citation Format: Shih-Shin Chang, Hirohito Yamaguchi, Mien-Chie Hung. Cisplatin-resistant cells possess collateral sensitivity to folate antimetabolites. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr B03.
SP0106 Ehealth Literacy on Rheumatic Diseases: Analysing the Power of the Internet: Health Talk Online - Patients' Experience of Gout
Authors: J. Richardson
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Gout is the most common form of inflammatory arthritis, affecting around 1-2% of the population in the UK. Worldwide, it is increasing in prevalence due to a variety different factors. However, we know little about patients9 experiences of this condition. Our study therefore aimed to explore people9s experiences of gout and to produce a section on gout for the website Health Talk Online. This award-winning website currently covers over 75 different health conditions and provides reliable, experience -based information about illnesses and health problems, for patients and health professionals. We carried out 43 semi-structured one-to-one interviews with a diverse sample of people with gout in the United Kingdom. Interviews were video- and/or audio recorded, transcribed and analysed thematically. This presentation will focus on what patients told us about where they looked for information on gout, what sort of information they found and what was valued. People spent a lot of time looking for information when they were first diagnosed, with information about causes and how to prevent attacks being particularly important. Some people wanted to know more about medications and possible side effects, and many looked for information about diet. Some people wanted as much information as possible, while others preferred not to know too much. Many people found a lot of conflicting and confusing information about diet and complementary treatments on the internet. Understanding the broad range of patient experience can be helpful to both patients and practitioners. For patients, knowing more about other people9s experience can help them to make decisions about their own care. For practitioners, knowing more about patients9 views and experiences may help them in supporting patient choices. This can also apply to other common inflammatory arthritis conditions and I will also talk briefly about a developing project on people9s experience of polymyalgia rheumatica (PMR). <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6112
AB1423-HPR One year follow-up of web-based medical folder accessible by patients suffering from rheumatoide arthritis (RA) and their rheumatologists (meteor software)
Authors: M. Mezières, S. Paternotte, C. Le Bourlout, M. Dougados
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systematic evaluation of disease activity using a composite index such as DAS results in benefit for RA patients via an appropriate treatment strategy. Involving patients in such procedure might facilitate its implementation. <h3>Objectives</h3> To evaluate the use of the online individual medical folder (e.g. METEOR) by RA patients and their rheumatologists. <h3>Methods</h3> Design: Mono-center observational study. Patients: RA patients with a personal access to internet were invited to participate. Study procedure: After elaboration of his/her personal file by a clinical research nurse using the METEOR software (www.meteorapplication.com), patients were educated on how using the software and in particular how filling the HAQ score. Outcome measures: Both the rheumatologist's and patient's interest were assessed by the number of DAS (by the rheumatologist) and number of HAQ evaluations (by the patient) notified in METEOR software during one year, compared with the number of visits in the hospitals. <h3>Results</h3> From March 2009 to December 2011, 70 out of the 155 patients participating at the METEOR program had a follow-up of at least one year. The 70 patients had the following characteristics: mean age 53.2 yrs (28.8-75), female gender (80%), mean disease duration 9.3 yrs (0-29). The majority of the patients (89%) were receiving at least one DMARD including a biologic in 35 patients (50%). The baseline DAS and HAQ were 2.78 (0-6.96) and 0.55 (0-2.38) respectively. During the one year follow-up period, DAS and HAQ were entered in the METEOR software by 60% and 63% of the patients respectively and at least twice by 36% and 39% respectively. DAS was available on the METEOR Website for only 50% of the visits. Moreover, 22 patients (31%) entered HAQ data at home at least once during the one year follow-up period. <h3>Conclusions</h3> Our study suggests that despite a high interest of the patients while presenting them the METEOR initiative, such interest seems to decrease overtime probably due to the poor participation/collaboration of their rheumatologists. <h3>Disclosure of Interest</h3> None Declared
P403 IN VIVO ASSESSMENT OF ABC TRANSPORTER ACTIVITY USING [F]CIPROFLOXACIN AND PET-MR SCANNING IN MICE FED WITH NORURSODEOXYCHOLIC ACID
Authors: E. Halilbasic, T. Wanek, F. Cuperus, T. Claudel, M. Müller, O. Langer, M. Trauner
Journal: Journal of Hepatology (2014)
GENDER DIFFERENCE IN LONG-TERM CLINICAL OUTCOMES FOLLOWING PERCUTANEOUS CORONARY INTERVENTION DURING 1984-2008
Authors: Ryo Naito, Katsumi Miyauchi, Hirokazu Konishi, Shuta Tsuboi, Manabu Ogita, Takatoshi Kasai, Hiroshi Tamura, Shinya Okazaki, Kikuo Isoda, Hiroyuki Daida
Journal: Journal of the American College of Cardiology (2015)
IMPACT OF INCREASING PHYSICAL ACTIVITY OVER 12 WEEKS IN PREVIOUSLY SEDENTARY OLDER ADULTS: A 1-YEAR FOLLOW UP
Authors: Mobin Ahmed Malik, Tisha Suboc, Scott J. Strath, Jingli Wang, Michael J. Tanner, Rong Ying, Michael Widlansky
Journal: Journal of the American College of Cardiology (2015)
Concomitant medication (CM) use in phase I and II cancer clinical trials (CCT): Effects on trial eligibility and potential interactions with study medications.
Authors: M. Benjamin, K. K. Curtis, R. Tibes, R. K. Ramanathan, D. D. Von Hoff, K. Wright, G. S. Jameson, M. J. Borad
Journal: Journal of Clinical Oncology (2010)

6092 Background: CM use may result in ineligibility for CCT due to CM-study drug interactions, CM prolongation of QT interval, and alteration of study drug absorption by CM. Few studies have examined the impact of CM use on CCT eligibility. We reviewed records of patients (pts) on CCT at a large, dedicated clinical trials center to better understand this important topic in early stage drug development. Methods: The records of 274 serial pts referred for a CCT were reviewed. Patient demographics, CM identities and classes, reasons for discontinuation (D/C) of CM, and incidence of CM substitution (sub) were recorded. CM-study drug CYP interactions were documented. Statistical analysis was performed using descriptive statistics. Results: Pt demographics were: median age-61 years (range 24-90 years); sex-145 male (53%). 273 of 274 pts (99.6%) were taking CM, with a median of 8 CM per pt (range 0-42). CM D/C occurred in 67 cases (24%). The most common class of CM D/C was herbal CM (16 cases, 24%). Reasons for CM D/C were: prohibition by protocol (n = 32, 48%); potential CM-study drug interaction (n = 25, 37%); other (n = 10, 15%). A potential CM-study drug CYP metabolism interaction was noted in 122 cases (45%). CM potentially weakly decreased study drug metabolism in 52 cases (43%), and potentially strongly decreased study drug metabolism in 17 cases (14%). Study drug potentially weakly decreased CM metabolism in 39 cases (32%), and potentially strongly decreased CM metabolism in 28 cases (23%). CM sub was possible in 13 cases (13%). In 2 cases (1%), pts were ineligible for trials because CM could not be D/C or sub. Conclusions: Almost all cancer pts on CCT use CM. By careful assessment and substitution or D/C of CM, most pts are eligible for CCT. No significant financial relationships to disclose.
Abstract 2088: Detection of <i>PIK3CA</i> somatic mutations in cell-free DNA of breast cancer patients by high-resolution melting curve analysis
Authors: Christina Schiza, Sofia Farkona, Maria Chimonidou, Panos Vorkas, Nikos Malamos, Vasilis Georgoulias, Evi S. Lianidou
Journal: Cancer Research (2012)

Abstract Introduction: Somatic mutations in the gene encoding for the phosphatidyl-inositol 3-kinase (PI3K) catalytic subunit, PIK3CA, have been discovered in many different human cancers. We have recently developed a high-resolution melting curve analysis method for the detection of the three hotspot mutations of PIK3CA gene (Vorkas et al, J of Mol Diagn 2010). The aim of our study was to evaluate this method for the presence of PIK3CA mutations in cell-free DNA (cfDNA) circulating in plasma of breast cancer patients and healthy individuals. Patients and methods: cfDNA was isolated from plasma (200μL) of 30 patients with operable breast cancer, 45 patients with metastatic breast cancer and 12 healthy donors. After DNA extraction, real-time PCR was performed in triplicate for all samples in the LightCycler (Roche), in the presence of LC-Green Plus saturating dye (Idaho Technology Inc.). High-resolution melting curves were obtained with HR-1 High Resolution Melter (Idaho Technology Inc.). Results: We identified 15 cfDNA samples mutated out of 75 tested (20%). 3/75 (4%) cfDNA samples were mutated within the exon 9 amplified region, and 12/75 (16%) cfDNA samples were mutated within exon 20 (31.6%). In operable breast cancer 1/30 (3.3%) cfDNA sample was mutated in exon 9 and 3/30 (10%) cfDNA samples were mutated in exon 20, while in metastatic breast cancer 2/45 (4.4%) cfDNA samples wer mutated in exon 9 and 9/45 (20%) cfDNA samples were mutated in exon 20. PIK3CA mutations were not detected in any of the 12 cfDNA samples from healthy donors, used as negative controls. Conclusions: Using High-Resolution Melting curve Analysis (HRMA) PIK3CA gene mutations were detected in cfDNA circulating in plasma of patients with operable and metastatic breast cancer, but not in plasma of healthy individuals. The prognostic significance of this finding will be evaluated when a longer follow up period will be completed for these patients and a larger number of clinical samples will be analyzed. 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 2088. doi:1538-7445.AM2012-2088
Adjuvant Systemic Therapy and Survival after Breast Cancer
Authors: Ivo A. Olivotto, Chris D. Bajdik, Ian H. Plenderleith, Christopher M. Coppin, Karen A. Gelmon, Stewart M. Jackson, Joseph Ragaz, Kenneth S. Wilson, Ann Worth
Journal: New England Journal of Medicine (1994)

We examined the effect of adjuvant systemic therapy on survival after breast cancer among the residents of the Canadian province of British Columbia. Data on survival were collected for all women in whom breast cancer was diagnosed in British Columbia during each of three calendar years chosen to represent different province-wide treatment recommendations: 1974, when no adjuvant systemic therapy was recommended; 1980, when adjuvant chemotherapy was recommended only for premenopausal women with node-positive disease; and 1984, when adjuvant chemotherapy was also recommended for premenopausal women with node-negative disease and lymphatic, vascular, or neural invasion and tamoxifen was recommended for postmenopausal women with involved lymph nodes or lymphatic, vascular, or neural invasion unless their tumors were negative for estrogen receptors.For women less than 50 years of age, disease-specific survival at seven years (i.e., with censoring of data on women who died from causes other than breast cancer) improved from 65.2 to 76.3 percent between 1974 and 1984 (P = 0.008), and overall survival improved from 64.8 to 74.6 percent (P = 0.02). For women from 50 through 89 years of age, disease-specific survival at seven years improved from 62.5 to 70.4 percent between 1980 and 1984 (P = 0.001), and overall survival improved from 53.9 to 58.3 percent (P = 0.05). The timing of the improvements in survival correlated with the introduction of adjuvant systemic therapy in each group.Survival among women with breast cancer improved significantly in a geographically defined population during the period when adjuvant systemic therapy became widely used.
Sudden Unilateral Corneal Clouding in an Infant
Authors: Anil K Mandal, Vijaya K Gothwal
Journal: New England Journal of Medicine (2013)

A healthy 3-month-old boy was brought to the emergency department with acute onset of corneal edema of the left eye. One hour before presentation, his parents noticed that the left cornea was cloudy and the right eye was normal after he had been crying.
FRI0022 Relationships between radiographic damage, shared epitope alleles and circulating cytokines in dmard-naïve early ra patients
Authors: M. M. Ally, B. hodkinson, P. W. A. meyer, E. musenge, M. tikly, R. anderson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Although therapeutic targeting of humoral and cellular inflammatory biomarkers has improved outcomes in subsets of patients with severe RA, the identification of novel targets based on insights into disease immunopathogenesis remains a priority. <h3>Objectives</h3> to identify relationships between radiographic damage, circulating cytokines/chemokines/growth factors, and shared epitope (SE) risk alleles classified according to the Du Montcel system <h3>Methods</h3> DMARD-naïve, predominantly African female patients (n=142) with early RA (&lt;2 yrs) were assessed radiographically with the modified Larsen score, measurement of serum cytokines using Luminex xMAP multiplex technology, and PCR typing of the HLA-DRB1 allele classified risk allele positive (S2 and /or S3P) or risk allele negative (S2 and/or S3D and/or X). <h3>Results</h3> 82 (58%) carried the SE risk allele, 52% had erosive disease, and the mean Larsen score was 22(SD 12,6). There was no significant difference in the Larsen score between risk allele positive or negative group of patients. In the risk allele -ve patients, but not risk allele +ve group, Larsen scores were positively and significantly correlated with IL-7, IL-8, and VEGF (see table 1). No correlations were noted with the other circulating biomarkers. In the risk allele -ve group, IL-7 and VEGF also correlated positively and significantly with erosive disease. Inter-correlations between the various inflammatory biomarkers were generally strongest in the SE risk allele-negative group with notably increased correlations between IL 7 and IL 2/IL 4. <h3>Conclusions</h3> IL-7 and VEGF, which promote osteoclastogenesis and neovascularization respectively, were found to correlate with erosive disease in SE risk allele-negative patients. These observations are compatible with possible differences in the immunopathogenesis of RA in SE risk allele-negative and –positive patients, identifying IL-7 and VEGF as potential targets for biologic therapy in the former group. <h3>References</h3> Hartgring SAY et al. Interleukin-7 induced immunopathology in arthritis. Ann Rheum Dis 2006;65(Suppl):69-74. P.W. Meyer, B et al., "Circulating cytokine profiles and their relationships with autoantibodies, acute phase reactants, and disease activity in patients with rheumatoid arthritis," <i>Mediators of Inflammation</i>, 2010;2010:158514, Epub 2011 <h3>Disclosure of Interest</h3> None Declared