tbuckley/cabot-search huggingface dataset:
TM-09 * INHIBITION OF GLIOMA CANCER STEM CELL BY COMBINATION OF 2-DEOXYGLUCOSE AND METFORMIN
Authors: E. Kim, P. Kim, S.-G. Kang
Journal: Neuro-Oncology (2014)

Glioma cancer stem cells (gCSCs) are known to play an essential role in tumor formation, maintenance, and progression. Treatment outcome of a glioblastoma, the most malignant form of gliomas, is still unsatisfactory in spite of any combination of current best treatment modalities. Because the presence of residual surviving gCSCs is thought to be a main reason for treatment-resistance and the source of recurrence, new and innovative therapeutic approaches targeting gCSCs could be an important therapeutic modality to overcome resistance to current anti-cancer treatments. It's known that deprivation of tumor bioenergetics by dual inhibition of aerobic and anaerobic pathways may work for cancer treatment. This study investigated whether the combination of 2-deoxygluxose (2-DG) and metformin inhibit gCSCs. We evaluated the antitumor activity of 2-DG, metformin alone, and combination of 2-DG and metformin. 2-DG alone did hardly affect cell viability, however, metformin alone showed dose-dependent antitumor effect on gCSC line. Moreover, 2-DG in combination either with 5mmol/L or 15mmol/L of metformin induced 100% of cell death. When gCSC line was treated with combined 2-DG and metformin, surface markers of gCSC such as Nestin, CD133 and stemness-regulating transcription factors including Sox-2 and Notch4 were both suppressed. On the contrary, adherent cells expressing Olig2, GFAP, Tuj1 were newly formed from neurospheres under treatment of combined 2-DG and metformin, which implies neuro-glial differentiation. 3D invasion test showed that treatment of combined 2-DG and metformin significantly reduced invasiveness of gCSCs with decreased expression of surface markers for invasion like Snail, zeb1, β-catenin and N-cadherin. In mouse xenograft models, 2-DG plus metformin treatment effectively inhibited tumor growth. The combination of 2-DG and metformin may be helpful in the treatment of gliomas by targeting gCSCs.
Differentiation of Benign From Malignant Nodules by Accumulation of Tc-99m Pertechnetate Using Tl-201 Delayed Scans
Authors: YOSHIHIRO OKUMURA, YOSHIHIRO TAKEDA, SHUHEI SATO, MITUHARU SHIMIZU, MEGUMI KOMATSU, OSAMU HONDA, TOMIO NAKAGAWA, HARUTAKA NIIYA, YOSHIO HIRAKI
Journal: Clinical Nuclear Medicine (1998)

Thyroid carcinoma usually is characterized by a nonfunctioning or "cold" nodule depicted on the Tc-99m scan. Twelve patients with functioning "hot" thyroid nodules underwent thyroidectomy (nine hemithyroidectomies, two nodulectomies, and one subtotal thyroidectomy). Histologic examination revealed that five patients (42%) had malignant nodules (papillary carcinoma in two and follicular carcinoma in three). Of the seven patients with benign nodules, five had follicular adenoma and two had adenomatous hyperplasia. Tl-201 scanning (early and delayed) was performed at the same time as Tc-99m scanning. Only one of the seven benign nodules showed accumulation on the delayed Tl-201 scan, whereas all five malignant nodules showed accumulation. The delayed Tl-201 scan is useful for the differentiation of benign from malignant nodules that show accumulation of Tc-99m pertechnetate.
Case 21-2000
Authors: Thomas F. Tracy, Fiona M. Graeme-Cooke
Journal: New England Journal of Medicine (2000)

Presentation of CaseA 13-year-old boy was admitted to the hospital three years and eight months before the diagnostic procedure because of abdominal pain.Periumbilical pain had begun the day before the initial admission, after the patient had eaten cookies and an apple. He slept poorly that night, and by the next morning the pain had shifted to the right lower quadrant of the abdomen. During that day the temperature remained normal. In midafternoon he vomited 240 ml of red liquid after consuming a soft drink and was brought to this hospital. There was no history of fever, sweats, chills, . . .
EFFECT OF TRUNK MOTOR CONTROL TRAINING ON HIP MUSCLES IN ELITE FOOTBALL PLAYERS
Authors: D Mendis, W Stanton, J Hides
Journal: British Journal of Sports Medicine (2014)

Background Decreased size and altered function of lumbo-pelvic muscles has been found in elite athletes with low back pain (LBP). Previous research has shown that training trunk neuromotor control in elite football players with and without LBP improved the size and function of muscles important in stability of the lumbo-pelvic region. Hip muscles also contribute to lumbo-pelvic stability and imbalances in these muscles have been associated with LBP in collegiate athletes. Objective To investigate if a motor control intervention program targeting trunk muscles affects hip muscle size in elite football players with and without LBP. Design The trial was delivered as a stepped-wedge design with 3 treatment arms: 15 weeks intervention, 8 weeks intervention and a wait-list control who received 7 weeks intervention toward the end of the playing season. Setting Elite level football club in the National Australian Football League (AFL). Participants Complete training squad of 46 elite players from an AFL club. Interventions The motor control program, delivered over the playing season, involved performance of voluntary contractions of the trunk muscles with feedback from ultrasound imaging. Main outcome measurements Cross-sectional areas of the iliacus, psoas, iliopsoas, sartorius, gluteus minimus, gluteus medius and upper gluteus maximus muscles were measured from magnetic resonance images. Results The motor control training program was associated with an increase in hip muscle size especially for those with LBP (P&lt;.01). Conclusions The motor control training program, which targeted proximal muscles of the lumbar spine, had an effect on both trunk and hip muscles. Neuromuscular control training programs may benefit more muscles in the kinetic chain than trunk muscles alone. This finding may be due to the functional components of the motor control program that encouraged optimal trunk and femoro-pelvic alignment when load was added in functional weight bearing positions.
METABOLIC SYNDROME IS ASSOCIATED WITH PRECLINICAL ALTERATIONS IN MYOCARDIAL MICROSTRUCTURE
Authors: Youssef Rahban, Harpaul Sandhu, Pranoti Hiremath, Fuzhong Qin, Donohue Courtney, Deborah Siwik, Susan Cheng, Wilson Colucci, Jennifer E. Ho
Journal: Journal of the American College of Cardiology (2016)
Abstract LB-482: MiRNA replacement therapy <i>in vivo</i>: antitumor effects of nanoparticle-formulated miR-145 and miR-33a, and targeting of Pim-1
Authors: Ulrike Weirauch, Ahmed Fawzy Ibrahim, Maren Thomas, Kerstin Lange-Grünweller, Arnold Grünweller, Roland K. Hartmann, Achim M. Aigner
Journal: Cancer Research (2012)

Abstract Various miRNAs are aberrantly expressed in cancer. In colon carcinoma, decreased levels of the pro-apoptotic and anti-proliferative miRNA-145 are observed, while the role of miR-33a has not been analysed yet. In this study, we demonstrate the tumor-inhibitory role of miR-33a and newly identify the proto-oncogenic kinase Pim-1 as its direct target. Comparably to siRNA-mediated knockdown of Pim-1, miR-33a reduces Pim-1 expression and thus inhibits proliferation in leukemia and in colon carcinoma cells by decelerating cell cycle progression. Most recent in vitro and in vivo data from our group further establish the so far unknown functional relevance of Pim-1 in colon carcinoma and identify Pim-1 as attractive target gene. Among others, RNAi-mediated Pim-1 knockdown reduces tumor growth, induces apoptosis and leads to major changes in oncogenic signal transduction, including the inhibition of STAT3. The therapeutic application of miRNAs strongly relies on the development of suitable delivery tools, and we introduce polyethylenimine (PEI)-based nanoparticles for systemic or local miRNA administration in vivo. PEIs mediate miRNA protection, delivery to target organs, cellular uptake and intracellular release. MiRNA replacement therapy through systemic or local injection of PEI/miR-145 complexes results in efficient miRNA delivery and in antitumor effects in s.c. colon carcinoma xenograft mouse models. Likewise, tumor growth inhibition is observed upon treatment with PEI-complexed miR-33a. This is due to the miR-33a-mediated downregulation of Pim-1 expression, comparable with the Pim-1 knockdown through PEI/siRNA complexes. Conclusions: (i) The PEI-complexation of miRNAs represents a novel strategy in miRNA replacement therapy, (ii) miR-145 / miR-33a may be promising candidate miRNAs, and (iii) Pim-1 is a newly identified, attractive target gene in colon carcinoma. 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 LB-482. doi:1538-7445.AM2012-LB-482
AB0929 Differences regarding the amount and frequency of alcohol intake and smoking between european and non-european patients living in the same environment and suffering from spondylarthritis according to the ASAS criteria (axial, peripheral or both):
Authors: E. Roussou, D. Lunda Ngandu, S. Intzes, A. Georgiou
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To assess differences in the social habits (alcohol, smoking) in European and non European patients with spondylarthritis (SpA). <h3>Methods</h3> From a registry of patients with psoriasis a total of 134 patients (87 European, 47 Non-European) fulfilling ASAS criteria for SpA (4 patients had axial disease, 113 patients had peripheral disease, 17 patients had both axial and peripheral disease) were questioned regarding their alcohol and smoking habits. In the alcohol intake section patients were asked a) whether they drink alcohol or not and b) whether they drink socially, daily or never. In the smoking section patients were asked to reply whether they were current smokers, ex-smokers or never smoked. <b>Results:</b> Mean age of the total group (t) was 50.1 year (y) ±13.4 [European [E] = 52.2 y ±4.1; non European [nE] = 46.5 y ±11.4; p=0.01]. Age at diagnosis (t) was 43.5±4.5; E=45.2±15.7; nE=40.6±11.9; Disease duration (t) 8.5±8.4; E=8.3±8.9; nE=8.9±7.9. Delay in diagnosis (t) 5.3±7.9; E=5.4±8.3; nE=5.1±7.1. BASDAI of the total group was 6.1±2.8 and well being (t) 6.1±2.7 with no difference between E and nE in both items. There were 130/134 (97%) replies on the alcohol question, 127/134 (94.7%) on the frequency of alcohol and 124/134 (92.5%) on the smoking. Table shows alcohol intake, frequency and smoking in European and non European and statistical significant levels. Looking at gender differences with regards to alcohol and smoking in European and non European, there are no differences between European men and women. (p=0.2, and p=0.8 for alcohol and smoking respectively). There were however statistical significant differences in both alcohol and smoking in non European between men and women in that men consume more of both. [Pearson's chi square 5.840; df=1; p=0.01 for alcohol and pearson's chi square 6.348; df=2; p=0.04 for smoking.] <h3>Conclusions</h3> Significantly more European patients drink alcohol (p&lt;0.005), and drink it in increased frequency compared to non Europeans (p&lt;0.005). In addition sgnificantly more Europeans are current smokers (p&lt;0.005.) comapred to non Europeans. There are no gender differences among European male and females in both alcohol and smoking but significantly more male non European dring alcohol and smoke compared to female non European. <h3>Disclosure of Interest</h3> None Declared
Ambenonium in the Treatment of Urinary Retention and Constipation
Authors: Edward M. Mahoney, Dale G. Friend, J. Hartwell Harrison
Journal: New England Journal of Medicine (1959)

TRINARY and fecal retention, either alone or ^-' together, poses a serious problem in the management of the patient. Unfortunately, these complications are appearing much more often than they were a few years ago. This is, for the most part, a result of the introduction and use of numerous highly potent drugs for the treatment of a variety of conditions from hypertension to Parkinson's disease.The ganglionic-blocking drugs widely used in the treatment of hypertension are frequent offenders, and all of them have a depressant action on the bowel and bladder that, in some patients, leads to serious loss of . . .
Abstract 4042: Loss of imprinting at the 14q32 locus contributes to osteosarcoma
Authors: Jingmin Shu, Lihua Li, Branden Moriarity, Venugopal Thayanithy, Logan G. Spector, David A. Largaespada, Clifford J. Steer, Subbaya Subramanian
Journal: Cancer Research (2012)

Abstract Osteosarcoma (OS) is the most common primary bone malignancy affecting children and young adolescents. Downregulation of microRNAs at 14q32 locus is implicated in the pathogenesis of OS. However, array comparative genome hybridization did not show any DNA copy number loss at this locus. We hypothesized that epigenetic alterations may regulate genes and microRNAs present in this locus and contribute to the development and progression of OS. Here, we show that OS is characterized by a selective loss of imprinting (LOI) at 14q32 locus. LOI at the 14q32 locus was unique to OS, compared with 10 other cancer cell lines representing 6 tissue types. Furthermore, the average demethylation at 14q32 locus was 24%, but the global demethylation as determined by LINE-1 retrotransposons was only 7%. We also found LOI in H19, MEST, and PEG3 loci in OS samples, albeit less frequently. LOI at the 14q32 locus is highly prevalent (82.6%, 19 out of 23) only in OS patients with early-onset (12-30 years of age) of the disease. Imprinted genes at 14q32 locus were downregulated in OS due to histone modifications and the locus was controlled by bivalent domain enriched with both K4-3m and K27-3m. We determined the tumor suppressor function of this locus by overexpression of 3 imprinting genes, DLK1, RTL1 or DIO3 in SaoS2 cells. We found that all 3 genes inhibited cell proliferation and enhanced apoptosis. We also tested methylation patterns using matched buccal DNA samples obtained from OS patients and their parents. Interestingly, loss of imprinting at 14q32 locus was found in most of the OS patients and their parents, suggesting that children might be predisposed to developing OS by inheriting the instability of imprinting at this genomic site. To determine if loss of imprinting at 14q32 locus is the driving mechanism, or a secondary genetic event, we evaluated tumor tissues obtained from p53LSLR270H/;Osx-Cre mice OS models. These mice developed OS at 8-12 months (potentially representing the late-onset (&amp;gt; 30yrs) of human OS). LOI was found only in 33% of mice OS samples, which is in agreement with the low rate of LOI detected in late-onset human OS. In conclusion, our findings suggest that LOI at the 14q32 genomic locus is likely a contributing event in the pathogenesis of OS. 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 4042. doi:1538-7445.AM2012-4042
Healing the Syk through Kinase Inhibitors
Authors: Juan Rivera, Robert A. Colbert
Journal: New England Journal of Medicine (2010)

Rheumatoid arthritis is a chronic, systemic inflammatory disease that affects close to 1% of the population. It is manifested principally as an attack on peripheral joints and may lead to marked destruction and deformity of joints, with considerable disability. Rheumatoid arthritis is characterized by the production of autoantibodies, synovial inflammation with formation of pannus tissue, and erosion of the underlying cartilage and bone. Despite considerable efforts and significant advances, the cause of rheumatoid arthritis and its pathogenesis remain incompletely understood.Effective treatment of new-onset rheumatoid arthritis involves establishing an early diagnosis and beginning disease-modifying antirheumatic therapy that can prevent or . . .
Abstract LB-157: Overcoming T-regulatory effects towards developing a more effective immunotherapy targeting multiple myeloma
Authors: Lung-Ji Chang, Shuhong Han, Starlyn Okada, Ekta Patel, Li-jun Yang, Jan S. Moreb, Hanspeter Pircher, Lia E. Perez, Melissa Alsina
Journal: Cancer Research (2011)

Abstract Recent progress in dendritic cell (DC) and T cell therapies has offered a new avenue in treating multiple myeloma (MM). We have reported that MM patients' DCs cannot effectively present MM antigens and, instead, preferrentially activate T regulatory cells (Tregs). Furthermore, the MM cells actively suppress patients' DC and T cell functions (Han et al. 2008 Mol Ther. 16, 269–279). Therefore, an effective immunotherapy must overcome immune tolerance to the cancer cells and effectively expand functional MM-specific effector cells. To obtain critical data about MM patient's immune status, a longitudinal study of Treg cells before and after treatments of twenty MM patients was conducted. Patients' bone marrow (BM) and peripheral blood (PB) specimens were collected in the first visit and the follow up visits during treatment. Treg cell populations were examined using antibodies against CD4, CD25, CD127 and Foxp3. At the same time, naïve versus memory phenotype was assessed using antibodies against CD45RA, CCR7 and CD27. Besides the above markers, the surface molecule KLRG1 reflecting T cell senescence and longivity was also detected by flow cytometry. Analysis of Tregs at different time points showed a clear trend of gradual increase in Treg population both in the BM and PB of the MM patients; compared with healthy donors, MM patients' Tregs expand more than two to three folds. Surface marker analysis suggests that the expanded Tregs are mostly memory effector cells, which coincides with a decrease in the ratio of naïve Tregs. Analysis of MM-specific T cell responses by examining effector cytokines and cytolytic activities against autologous tumor cells revealed that BM contained more cytotoxic T cells than did PB. Increased expansion of MM-specific immune effector cells in culture was observed when Treg activities were suppressed using various immune modulators. Further understanding of Treg-mediated cancer tolerance will be essential to develop clinically more effective immunotherapy towards improved survival of MM patients. 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 LB-157. doi:10.1158/1538-7445.AM2011-LB-157
A4.5 Arthritis induces early bone high turnover, structural degradation and mechanical weakness
Authors: B Vidal, R Cascão, AC Vale, I Cavaleiro, MF Vaz, JA Brito, H Canhão, JE Fonseca
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> We have previously found in the chronic SKG mouse model of arthritis that long standing (5 and 8 months) inflammation directly leads to high collagen bone turnover, disorganisation of the collagen network, disturbed bone microstructure and degradation of bone biomechanical properties. The main goal of the present work was to study the effects of the first days of the inflammatory process on the microarchitecture and mechanical properties of bone. <h3>Methods</h3> Twenty eight Wistar adjuvant-induced arthritis (AIA) rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for comparison. After 22 days of disease progression rats were sacrificed and bone samples were collected for histomorphometrical, energy dispersive X-ray spectroscopical analysis and 3-point bending. Blood samples were also collected for bone turnover markers. <h3>Results</h3> AIA rats had an increased bone turnover (as inferred from increased P1NP and CTX1, p = 0.0010 and p = 0.0002, respectively) and this was paralleled by a decreased mineral content (calcium p = 0.0046 and phosphorus p = 0.0046). Histomorphometry showed a lower trabecular thickness (p = 0.0002) and bone volume (p = 0.0003) and higher trabecular separation (p = 0.0009) in the arthritic group as compared with controls. In addition, bone mechanical tests showed evidence of fragility as depicted by diminished values of yield stress and ultimate fracture point (p = 0.0061 and p = 0.0279, respectively) in the arthritic group. <h3>Conclusions</h3> We have shown in an AIA rat model that arthritis induces early bone high turnover, structural degradation, mineral loss and mechanical weakness.
VARS2 V552V Variant as a Prognostic Marker in Patients with Early Breast Cancer.
Authors: Y. Chae, H. Park, J. Jeong, J. Yang, M. Lee, J. Park, S. Kim
Journal: Cancer Research (2009)

Abstract Purpose: The present study analyzed the polymorphisms of DNA repair genes and their impact on survival of patients with early breast cancer.Patients and methods: A total of 240 patients with surgically resected early invasive ductal breast cancer were enrolled in the present study, where patients who underwent neoadjuvant treatment were excluded. The genomic DNA was extracted from paraffin-embedded tumor-free tissue or blood, and thirteen single nucleotide polymorphisms of 12 DNA repair genes were determined using the Sequenom Mass array system.Results: Among the target SNPs, VARS2 rs2074511 and POLE rs5744857 were found to correlate with relapse-free survival (RFS) after curative surgery in the log-rank test. There was no difference in the clinical and tumor characteristics according to the genotypes of these two coding variants except for the higher incidence of positive ER in patients with the GG genotype of POLE rs5744857 (p = 0.025). Multivariate analysis showed that the GG genotype of VARS2 V552V (rs2301717) was marginally associated with a better RFS than the combined AA and AG genotype (HR = 0.298; 95% CI = 0.089-0.995; p = 0.049). However, there was no significant association with overall survival.Conclusion: VARS2 V552V may be considered as a prognostic factor of survival in patients with early breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6055.
Case 38-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Andrew J. King, J. Andrew Carlson
Journal: New England Journal of Medicine (1993)

Presentation of CaseA 70-year-old man was admitted to the hospital for further management of a myocardial infarct.The patient had been well until three days earlier, when substernal pain developed and was accompanied by mild dyspnea, without nausea, vomiting, sweating, or radiation of pain. He was taken to another hospital within 1 1/2 hours, where laboratory studies showed that the urea nitrogen was 47 mg (17 mmol per liter) and the creatinine 2.4 mg per deciliter (210 μmol per liter). An electrocardiogram revealed an evolving anteroseptal myocardial infarct. Nitroglycerin, morphine sulfate, aspirin, atenolol, and streptokinase (1.5 million U by . . .