tbuckley/cabot-search huggingface dataset:
The safety of dose-dense liposomal-encapsulated doxorubicin in association with docetaxel (MyTax) in breast cancer.
Authors: M Mancini, K Cannita, A Santomaggio, M Tudini, F De Galitiis, M Morelli, A Rispoli, F Martella, G Porzio, M Pelliccione, V Cocciolone, P Lanfiuti Baldi, M Penco, S Romano, S Fratini, G Stifani, P Marchetti, C Ficorella, E Ricevuto
Journal: Cancer Research (2009)

Abstract Abstract #2157 Background: Liposomal-Encapsulated Doxorubicin (LED) shows equivalent efficacy, better cardiac tolerability at higher cumulative dose than conventional anthracyclines in breast cancer treatment.&amp;#x2028; Methods: Sixteen pts were enrolled in a dose-finding study of LED (TLC-D99 Myocet ®) associated to Docetaxel (TXT). Twelve pts were treated with a fixed TXT dose (50 mg/m2) and TLC-D99 at three dose levels, 40-45-50 mg/m2, days 1 and 15 every 2 weeks using an intra- and inter-patient approach; four pts wrere treated at the TLC-D99 recommended dose (50 mg/m2). Cardiac monitoring of LVEF was performed every two cycles; Precursor Brain Natriuretic Peptide (proBNP) and cardiac Troponin (c-TnI) before and after 24 h chemotherapy was evaluated.&amp;#x2028; Results: Breast cancer (BC) disease extension: metastatic (MBC), 8; locally advanced BC, 5; T2-T3 BC, 3. Previous chemotherapy: untreated, 11 pts; adjuvant, 5 pts. Enrolled pts for each dose-level: I, 7; II, 9; III, 14. Newly treated pts: I dose-level, 7; II dose-level, 3; III dose-level, 6. Valuable cycles for each dose-level in a total 77 cycles: I, 14; II, 21; III, 42. DLTs were observed in 3 pts, 21%, and 3 cycles, 4%: 2 cardiac, characterized by a 19% LVEF decrease and a symptomatic arrhythmia; one G4 hematologic resistant to G-CSF. DLTs for each dose-level by pts and cycles, respectively: I, 14% (1/7 pts) and 7% (1/14 cycles); II, no DLT in 9 pts and 21 cycles; III, 14% (2/14 pts) and 5% (2/42 cycles). Cumulative G3-4 toxicities by pts and cycles, respectively: cardiac arrhythmia 6% and 1,3%, cardiac general (symptomatic LVEF decrease), 6% and 1,3%; alopecia 81% and 65%; neutropenia resistant to G-CSF, 6% and 1,3%. Cardiac DLTs were observed in 2 elderly pts (&amp;gt;65 y). The 2 cardiac DLTs were observed in 2 out of 3 pts with pre-existing diastolic dysfunction. No pathologic increase of c-TnI levels was detected. Seven pts showed increased pro-BNP after chemotherapy; 1 of these with increased pro-BNP after chemotherapy, persistent the day 1 of each subsequent chemotherapy showed a DLT;&amp;#x2028; G2 toxicities by patients and cycles, respectively: asthenia 37% and 18%, stomatitis/mucositis 12% and 5%, nausea 31% and 12%. Median rDI of TLC-D99 was 25 mg/m2/w and TXT 25 mg/m2/w for pts, respectively. Preliminary efficacy in 16 assessable pts: LA-BC and MBC, 1 CR (pCR) 7 PR (OR 62%), 4 SD and 1 PD; T2-T3 BC, 2 PR and 1 SD.&amp;#x2028; Conclusion: dose-dense TLC-D99/Docetaxel association can be safely recommended at the dose of 50 mg/m2 for each drug. Docetaxel intensification is ongoing. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2157.
The history of the nature/nurture issue
Authors: Csaba Pléh
Journal: Behavioral and Brain Sciences (2012)

Abstract It is worthy to supplement Charney with two historical issues: (1) There were two rival trends in the rebirth of genetic thought in the 1960s: the universal and the variation related. This traditional duality suggested that heredity cannot be equated with genetic determinism. (2) The classical debates and reinterpretation of adoption/twin studies in the 1980s regarding intelligence suggested that the environment had a more active role in unfolding the genetic program.
1410 A RANDOMIZED, CONTROLLED, MULTICENTRE TRIAL COMPARING ENDOSCOPIC BAND LIGATION VERSUS TIPS IN CIRRHOTIC PATIENTS WITH RECURRENT VARICEAL BLEEDING NON-RESPONDING TO PHARMACOLOGICAL THERAPY
Authors: A. Ferlitsch, G. Ulbrich, A. Maieron, P. Salzl, T. Reiberger, B.A. Payer, M. Ferlitsch, M. Peck-Radosavljevic
Journal: Journal of Hepatology (2012)
Case 14-2011
Authors: David A. Chad, John H. Stone, Rajiv Gupta
Journal: New England Journal of Medicine (2011)

A 52-year-old woman was seen in the Neurology Clinic because of asymmetric sensory loss and paresthesias in both arms and legs, and impaired dexterity, of 5 months' duration, with asymmetric loss of tendon reflexes and no weakness. Diagnostic tests were performed.
AB0952 Intra-articular low molecular weight hyaluronate reduces platelet influx and matrix metalloproteinase-2 levels in synovial fluid of patients with knee osteoarthritis
Authors: A. Alunno, F. Luccioli, E. Falcinelli, G. Santoboni, S. Momi, E. Bartoloni, E. Petito, O. Bistoni, G. Mirabelli, P. Gresele, R. Gerli
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Matrix metalloproteinaeses (MMPs) are a large family of zinc-dependent endoproteinases that cleave several components of the extracellular matrix (ECM) and that are tightly regulated by tissue type MMP inhibitors (TIMPs). The joint cartilage and bone degradation that occurs in osteoarthritis (OA) is in part the consequence of an imbalance between MMPs and TIMPs. MMPs are released by several cell types, including platelets that have been recently shown to participate in the inflammatory processes of arthritis. Among platelet-derived MMPs, MMP-2 is of particular potential relevance for OA. Hyaluronic acid (HA), a core component of ECM, is a critical constituent of normal synovial fluid and plays a pivotal role in joint homeostasis. In clinical practice, intra-articular injection of low molecular weight HA (LMW-HA) has been used as visco-supplementation for knee OA and its therapeutic efficacy has been verified in a number of studies. <h3>Objectives</h3> Aim of the present study was to investigate the effect of a short treatment with LMW-HA on platelet derived MMP-2 in the synovial fluid and possible correlations with clinical response. <h3>Methods</h3> Nineteen patients with knee OA were enrolled. Synovial fluid (SF) samples were collected before (T0) and after 5 weeks of intra-articular LMW-HA (T1) (4 injections, one week apart). Western Ontario and McMaster Universities Arthritis Index (WOMAC) and global pain visual analogic scale (VAS) were also collected at both time-points. MMP-2 measurement in SF was performed by zymography. SF inflammatory cell count was performed optically, by a Burker Chamber, while platelets were counted by flow cytometry. <h3>Results</h3> SF MMP-2 levels, platelet activation, platelet, monocyte and eosinophil numbers, were all significantly reduced at T1, while lymphocyte and synoviocyte number was not affected. A direct correlation between platelet number and MMP-2 concentration in SF was observed at both time-points (p&lt;0.01). Patients achieved a good clinical response with reduction of all WOMAC items and VAS pain (all p&lt;0.0001) <h3>Conclusions</h3> The results of the present study show that LMW-HA decreases the intra-articular amount of platelets and of MMP-2. These data suggest a potential role for platelets in cartilage degradation in OA, possibly by the local release of MMP-2. LMW-HA, besides its symptomatic benefit, may play a role in slowing down cartilage degradation and eventually OA progression. <h3>References</h3> Wang CT et al. Osteoarthritis and Cartilage 2006;14:1237. Falcinelli E et al. Br J Haematol 2007;138:221. <h3>Disclosure of Interest</h3> None Declared
S66 Targeted in Vivo Imaging of the αvβ6 Integrin in Mice with Bleomycin-Induced Lung Fibrosis
Authors: AE John, J Luckett, R Awas, A Habgood, S Ludbrook, A Blanchard, A Perkins, RG Jenkins, JF Marshall
Journal: Thorax (2012)

<h3>Introduction</h3> TGFβ activation by αvβ6 integrins is central to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Furthermore, αvβ6 expression is increased in both human, and murine, fibrotic lung tissue. Current assessment of αvβ6 integrin levels in the lung requires immunohistochemical analysis of biopsy samples and repeated measurement of αvβ6. Although αvβ6 may be useful as a biomarker in IPF, currrent methods of detection make this approach clinically impractical. We have developed a non-invasive radioimaging CT/SPECT strategy for measuring αvβ6 integrin levels in the lungs facilitating the monitoring of disease progression and therapeutic response in IPF. <h3>Methods</h3> C57Bl/6 mice received intratracheal bleomycin or saline, 28 days prior to intravenous injection with Indium111-labelled A20FMDV2, an αvβ6 binding peptide derived from the VP1 coat protein of foot-and-mouth virus. A scrambled sequence peptide was used as control. Mice were injected with 5µg (10–24MBQ) of peptide and imaged by CT/SPECT scanning one, and three, hours later. <h3>Results</h3> Maximal binding of Indium<sup>111</sup>-labelled A20FMDV2 peptide was detected in skin, and lungs, of all mice at one hour. No significant binding was detected in mice injected with control peptide. Binding to αvβ6 integrin was significantly higher in the lungs of bleomycin, compared with saline, exposed mice (0.12±0.01MBQ vs 0.06±0.009 p&lt;0.001). Label was detected at similar levels in the bladder and kidneys of all mice suggesting similar administration and excretion kinetics. <h3>Conclusions</h3> Indium<sup>111</sup>-labelled A20FMDV2 peptide can specifically detect increased levels of αvβ6 integrin in the lungs of injured mice demonstrating that non-invasive imaging of the αvβ6 integrin in the development of fibrosis is possible.
Abstract 3576: Pixantrone is chemically and mechanistically related to mitoxantrone (Mito) and doxorubicin (Dox) but lacks their iron binding properties and myocyte toxicity in vitro
Authors: Miles P. Hacker, Tariq Ata, Korie Gesler, Jakub Mazur, Marc McKennon, Jack Singer
Journal: Cancer Research (2010)

Abstract The anthracyclines (Dox), anthracenediones (Mito) and anthrapyrazoles (losoxantrone) are all intercalating topoisomerase II inhibitors that have significant anti-tumor activity but have the potential to cause severe, treatment limiting cardiotoxicity. Each of these drugs contains at least one hydroxyquinone element capable of binding iron. Given the putative role of iron in free radical generation and drug induced cardiotoxicity, we synthesized Pixantrone (BBR 2778; Pix), an aza-anthracenedione heterocyclic compound devoid of hydroxyquinone moieties. Pix has recently successfully completed a Phase 3 clinical trial showing excellent anti-tumor activity. Results obtained in animal models demonstrated that Pix caused minimal cardiotoxicity in mice, even those pretreated with Dox. To determine whether Pix binds iron, we used a well established spectrophotometric method to assess drug: iron interactions. Adding increasing amounts of iron to a drug solution we noted the previously reported hypochromic and bathychromic shifts in drug absorption patterns for both Dox and Mito in a 3:1 and 2:1 drug: iron ratios, respectively. In contrast, no iron binding was noted when iron was added to Pix solution at iron: drug ratios ranging from 0.1 to 10.0. To assess the effect of pH on drug binding Pix was incubated with iron at pH of 5, 6, 7 and 8 and at no pH was iron binding detected. Further studies assessing the effect of incubation temperature (40C - 500C) and time of incubation (1 to120 min) demonstrated the lack of iron binding by Pix. Studies performed with the rat myocardial cell line H9C2 indicated that Pix (ID50&amp;gt;50 μg/ml) was far less toxic to confluent myocardial cells than doxorubicin (ID50∼1μg/ml). Further, Pix did not induce a significant increase in reactive oxygen species (ROS) compared to vehicle treated controls. In summary, our results demonstrate that the lack of iron binding and concomitant lack of SOD production may provide the mechanism for lack of cardiotoxicity in animals and an apparent decrease in cardiotoxic potential in humans for Pix. Our results also substantiate the idea that ROS are not necessary for tumor cell cytotoxicity. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3576.
Gastrointestinal Absorption of Calcium from Milk and Calcium Salts
Authors: Mudassir Sibtain Sheikh, Carol A. Santa Ana, Michael J. Nicar, Lawrence R. Schiller, John S. Fordtran
Journal: New England Journal of Medicine (1987)

Whether ingested calcium is absorbed more efficiently from freely water-soluble calcium salts than from poorly soluble salts is unclear. It is also unknown whether calcium is absorbed better from dairy products than from calcium salts. Using a method by which the net absorption of calcium can be accurately measured after a single dose, we studied eight healthy fasting subjects after they took a 500-mg dose of calcium from each of five calcium salts with various degrees of water solubility and from milk. The order of administration of the agents given was randomly determined. The mean (±SEM) net calcium absorption, in decreasing order of the solubility of the salts, was 32±4 percent from calcium acetate, 32±4 percent from calcium lactate, 27±3 percent from calcium gluconate, 30±3 percent from calcium citrate, and 39±3 percent from calcium carbonate. The differences in absorption were not statistically significant according to analysis of variance. On the basis of in vitro solubility experiments in acid mediums, we hypothesize that acid dissolution in the gastrointestinal tract may be responsible for the similar absorption of calcium from salts with widely different water solubilities. Calcium absorption from whole milk (31 ±3 percent) was similar to absorption from calcium salts. We conclude that calcium absorption from carbonate, acetate, lactate, gluconate, and citrate salts of calcium, and from whole milk, is similar in fasting healthy young subjects. Further study will be required to determine whether the results would be different in older subjects, with a higher dose of calcium, or if the calcium was ingested with food. (N Engl J Med 1987; 317:532–6.)
TRANSCATHETER CLOSURE OF VENTRICULAR SEPTAL DEFECT: RESULTS OF MIDTERM FOLLOWUP
Authors: Alex C. Egbe, Joseph Poterucha, Allison Cabalka, Nathaniel Taggart, Frank Cetta, Peter Pollak, Heidi Connolly, Guy Reeder, Donald Hagler
Journal: Journal of the American College of Cardiology (2015)
Financial Conflicts of Interest in Biomedical Research
Authors: Jerome P. Kassirer, Marcia Angell
Journal: New England Journal of Medicine (1993)

Financial conflicts of interest in medicine -- what they are and how to deal with them -- constitute one of the most contentious issues in our profession. Organized medicine and its critics have debated whether clinicians should gain financially from their practice in any way other than through their direct fees or salaries for service., and the academic community and its critics have debated whether medical researchers should gain financially from companies whose products they are evaluating. Opinions vary greatly -- from those advocating that all conflicts of interest be proscribed to those arguing for disclosure and caveat emptor to . . .
Treatment of a patient with seasonal premenstrual syndrome
Authors: B L Parry, N E Rosenthal, L Tamarkin, T A Wehr
Journal: American Journal of Psychiatry (1987)

The authors identified a patient who had premenstrual syndrome (late luteal phase dysphoric disorder) only in the fall and winter and was virtually asymptomatic during the spring and summer. On the basis of previous experience with seasonal affective disorder, they treated the patient with bright artificial light, which reversed her symptoms. On subsequent occasions they reversed this treatment effect with oral melatonin administration and found that propranolol and atenolol, beta-antagonists that inhibit the production of melatonin, had a therapeutic effect similar to that of light. They discuss the implications of these findings in relation to the importance of melatonin as a mediator of seasonal rhythms in biology.
Abstract SY05-02: Novel roles for microRNAs in metastatic progression
Authors: Sohail Tavazoie
Journal: Cancer Research (2012)

Abstract Metastasis is the major cause of death for cancer patients. This fact highlights the importance of committing significant research efforts to the elucidation of the molecular mechanisms underlying metastatic progression. We had previously investigated the mechanisms by which post-transcriptional mechanisms regulate metastatic gene expression. By using an in vivo selection mouse system that recapitulates human breast cancer metastasis in conjunction with a systematic and functional approach, we previously identified the first set of metastasis suppressor microRNAs (miR-335, miR-126, and miR-206), which strongly suppress human breast cancer metastasis to bone and lung of mice. These small non-coding RNAs are silenced in metastatic cell lines and in human metastatic primary breast cancer cell populations; they are also prognostic biomarkers in that their silencing in primary tumors of patients correlates with the likelihood of metastatic free survival in patients. Since our findings, a number of investigators have implicated these miRNAs in suppression of cancer progression in additional cancer types as well as silencing of these miRNAs in additional cancers. Also, many other microRNAs have been identified by the research community with metastasis suppressive capacities. Our group has focused our efforts on characterizing both the mechanisms by which miR-335, miR-126, and miR-206 mediate metastasis suppression as well as the mechanisms by which the expression of these molecules are silenced in highly metastatic cells. By applying an integrative experimental approach, we have begun delineating the molecular mechanisms by which these miRNAs suppress metastatic progression. While miR-335 acts cell-autonomously to suppress metastatic invasion and migration, miR-126 acts non-cell autonomously to modulate the recruitment of endothelial cells to breast cancer cells. We find that highly metastatic cells recruit mature endothelial cells with higher efficiency than poorly metastatic cells. MiR-126 suppresses endothelial recruitment by cancer cells through targeting of a novel set of pro-metastatic and pro-angiogenic genes that correlate in expression with human metastatic relapse. Mir-126 targets two distinct signaling pathways that promote cancer-mediated endothelial recruitment resulting in enhanced metastatic colonization. Our findings reveal the mechanisms by which a set of non-coding RNAs mediate metastasis suppression and reveal a novel set of miRNA targets with potential for therapeutic targeting in human breast 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 SY05-02. doi:1538-7445.AM2012-SY05-02
FRI0197 Use of BIOLOGICS in PM and DM in Sweden - A National Register Study
Authors: J. Svensson, A. Tjärnlund, J. Askling, M. Dastmalchi, B. Hanna, S. Magnusson Bucher, I. Lundberg
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Biologics have been used off-label in treatment of refractory polymyositis (PM) and dermatomyositis (DM) but their role in treating myositis is still unclear. <h3>Objectives</h3> In this study we aimed to describe the use of biologics in patients with PM and DM and their effectiveness and safety, based on national registries in Sweden. <h3>Methods</h3> Patients were identified by linking the national patient care registers to the prescribed drug register and the Swedish Rheumatology Quality register (SRQ). Effectiveness was based on an overall assessment of clinical outcome in the patient records, and changes in serum levels of creatine phosphokinase (CPK) and prednisolone dose. Clinical data were collected at start of treatment, at last follow up within 3 to 12 months or at discontinuation of treatment. Safety was evaluated by the number of patients stopping treatment due to adverse events within 12 months. Paired t-test was performed on the natural logarithm of CPK and prednisolone dose to compare changes before and after treatment. <h3>Results</h3> 63 patients treated with at least one biologic (35 PM, 28 DM, mean age 56 (12), 45 (71%) women,) were identified at 11 different centers between 2001 and 2012. All identified cases were refractory to previous medication with mean 2.5 (1.2) DMARDS beings used prior to start of biologic therapy. Multiple biological treatments were common with 7 patients treated with 2 different biologics and 8 patients treated with 3 different biologics. Rituximab (RTX) was the most often used biological agent (Table 1). No new treatment with anakinra (ANA) had been started after 2009 and no new treatment with TNF-inhibitors (TNFi) had been started after 2003. A statistical significant decrease in CPK was observed in the RTX group (p&lt;0,01 [JS1]). No other statistical difference could be found for any of the biologics when comparing CPK level and prednisolone dose before and after treatment. 3 patients stopped their treatment due to disease remission. They were all treated with RTX. <h3>Conclusions</h3> We found an increasing use of RTX and ABA in patients with PM and DM. In this population we found an overall favorable response to RTX and ABA in 2/3 of patients but less often to ANA and TNFi. A reduction of elevated CPK was observed in RTX treated patients. RTX and ABA seemed to be well tolerated by patients while more stopped treatment due to side effects in the anakinra- and TNFi-group. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4966