tbuckley/cabot-search huggingface dataset:
Abstract 3699: Novel combinatorial strategies for cancer chemoprevention using polymethoxyflavones from orange and atorvastatin
Authors: Peiju Qiu, Noppawat Charoensinphon, Jinkai Zheng, Mingyue Song, Ping Dong, Ryan Riddle, Hang Xiao
Journal: Cancer Research (2011)

Abstract Cancer is a complex disease, and multiple aberrant molecular events are driving forces for cancer progression. It is difficult to control cancer progression by a single agent. We investigated a novel approach to inhibit cancer cell growth by using polymethoxyflavones (PMFs, isolated from aged orange peel) and atorvastatin (Lipitor, a commonly used cholesterol-lowering drug) in combination. The goal is to identify combination regimen that can produce synergy in inhibiting human cancer cell growth. Our results on multiple colon and lung cancer cells demonstrated that permethoxylated PMFs, namely nobiletin and tangeretin, can synergistically interact with atorvastatin and produced much stronger inhibitory effects than either agent alone. On the other hand, the hydroxylated PMFs, namely 5-hydroxy nobiletin (5HN) and 5-hydroxy tangeretin (5HT) showed different interaction profiles with atorvastatin, i.e., 5HN produced strong synergy with atorvastatin while 5HT did not. Further mechanistic study demonstrated that the combination treatment with 5HN and atorvastatin for 24 hr caused extensive cell population accumulation in G0/G1 phase; whereas at 48 hr or longer, apoptosis was induced significantly. Our results also demonstrated that the combinational effects of 5HN and atorvastatin were associated with increased levels of p21Cip1/Waf1, and p27Kip1; decreased levels of CDK-2, CDK-4,CDK-6,Cyclin D1, Mcl-1 and hyper-phosphorylated Rb(Ser 780); and activation of caspase cascade. More importantly, we investigated the inhibitory effects of PMFs/atorvastatin combinations in an NNK-induced mouse lung tumorigenesis model, and our results demonstrated that dietary administration of nobiletin and 5HN in combination with atorvastatin caused potent inhibition of lung tumor formation in A/J mice. These inhibitory effects were much stronger than those produced by singular nobiletin, 5HN, or atorvastatin treatments at much higher doses. The isobologram-based statistic analysis confirmed that nobiletin, 5HN and atorvastatin produced strong synergy in inhibiting lung tumorigenesis in mice. In conclusion, the present work provided promising leads for future investigation on the novel combination of PMFs and atorvastatin as novel strategy for cancer chemoprevention. (This study was supported in part by NIH-CA139174, AICR-#10A044, CEAR pilot grant, and USDA Special Grant on Bioactive Foods). 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 3699. doi:10.1158/1538-7445.AM2011-3699
Molecular Basis of the Neurodegenerative Disorders
Authors: Joseph B. Martin
Journal: New England Journal of Medicine (1999)

Neurodegenerative disorders, which are chronic and progressive, are characterized by selective and symmetric loss of neurons in motor, sensory, or cognitive systems. Delineation of the patterns of cell loss and the identification of disease-specific cellular markers have aided in nosologic classification: senile plaques, neurofibrillary tangles, neuronal loss, and acetylcholine deficiency define Alzheimer's disease1,2; Lewy bodies and depletion of dopamine characterize Parkinson's disease3; cellular inclusions and swollen motor axons are found in amyotrophic lateral sclerosis4; and γ-aminobutyric acid–containing neurons of the neostriatum are lost in Huntington's disease.5 Mendelian inheritance can be demonstrated in many of these disorders . . .
AB1446-HPR Perceived exertion level in fibromialgic patients during the sit-to-stand test
Authors: J.F. Sauer, A.A. Berssaneti, P.C. Mango, F.R. França, A.P. Marques
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Fibromyalgic patients usually report fatigue and this symptom can increase the difficult to perform daily tasks, social and professional activities. Physical activities are often recommended to help patients dealing with the most important symptoms; however, there is no sense about fatigue complains during an exercise, since most studies have shown this symptom using questionnaires concerning previous events. <h3>Objectives</h3> The aim of this study was to evaluate the perceived exertion level during the sit-to-stand test in fibromyalgic patients. <h3>Methods</h3> Participated 49 subjects divided in two groups: Fibromyalgia Group (FMG n=34) and Control Group (CG n=15). All subjects performed the sit-to-stand test in a comfortable speed until exhaustion. Perceived exertion was evaluated by Borg Perceived Exertion Scale. Ratings of perceived exertion were reported in sit-to-stand test in tree moments: initial time (T1), after one minute (T2) and at exhaustion (T3). <h3>Results</h3> FMG presented the shorter total test duration (121.17 vs. 227.93 seconds; p&lt;0.000). At the beginning, the perceived exertion level was the same for both groups (p=0.06). After one minute, although both groups presented the same test speed (p=0.06), FMG have a higher level of perceived exertion (p=0.000). Until exhaustion, FMG have a decline in test speed (p=0.01), they were unable to perform the test during the same time than CG (61.17 vs. 167.93 sec; p&lt;0.000) but with the same perceived exertion level. <h3>Conclusions</h3> FMG was unable to perform the sit-to-stand test with the same performance as CG. FMG showed more intense perceived exertion level at the beginning, when the physical demand was similar for both groups (sit-to-stand during one minute). At the end of the test, when CG have higher physical demand (sit-to-stand test during 167.93 seconds) FMG have the same perceived exertion level. This information can be useful when patients are involved in physical activities groups with asymptomatic individuals. <h3>References</h3> Valkeinen H, Häkkinen A, Alen M, Hannonen P, Kukkonen-Harjula K, Häkkinen K. Physical Fitness in Postmenopausal Women with Fibromyalgia. Int J Sports Med 2008; 29:408–13. Vøllestad NK, Mengshoel AM. Relationships between neuromuscular functioning, disability and pain in fibromyalgia. Disabil Rehabil 2005;27:667–73. Borg GAV. Psychophysical bases of perceived exertion. Med Sci Sports Exerc 1982;14:377-81. Kivimäki M, Leino-Arjas P, Kaila-Kangas L, Virtanen M, Elovainio M, Puttonen S, Keltikangas-Järvinen L, Pentti J, Vahtera J. Increased absence due to sickness among employees with fibromyalgia. Ann Rheum Dis 2007;66:65-9. <h3>Disclosure of Interest</h3> None Declared
The Utility of Actinin-4 Protein Overexpression as a Predictive Biomarker for Therapeutic Effect of Adjuvant Chemotherapy to the Resected Lung Adenocarcinoma
Authors: H. Shiraishi, Y. Fujiwara, T. Kakuya, K. Tsuta, S. Watanabe, W. Huang, T. Yamada, H. Asamura, Y. Ohe, K. Honda
Journal: Annals of Oncology (2015)
Abstract 3631: NMDA receptors as possible therapeutic targets for cancer
Authors: Bonnie L. Akerman, Chenoa D. Allen, Nathan P. Sylvain, William G. North
Journal: Cancer Research (2011)

Abstract NMDA receptors constitute important calcium channels that are chiefly found within the central nervous system. Our laboratory has shown that these receptors are also expressed by human tumors such as neuroblastoma, small-cell lung carcinoma, breast cancer, and now ovarian and prostate cancer. The hypothesis being tested in our studies is that selective tumor expression of NMDA receptors is essential for cancer cell growth and proliferation. Human breast and ovarian cancer cells were treated with NMDA antagonists and agonists and changes measured in cell proliferation/growth and apoptosis. It was shown NMDA receptors are critically involved in cell growth of these cancer cells, and if blocked, cell growth is inhibited. Interestingly, the non-cancerous cell line, HEK 293, also expresses NMDA receptors, but NMDA antagonists were found to not influence growth of these cells. Receptor knock-down in MCF-7 breast cancer cells is being accomplished with lentavirus-coupled shRNAs, and selection performed for puromyocin resistance. We have thus far been able to selectively stably reduce NMDA receptor expression by 70-80% for a period of two weeks. The rate of cell growth was significantly decreased when the expression level of NMDAR1 is knocked down. The response of NMDA receptor knock-down cells to antagonists such as MK-801 and Mementine will be examined. Confirmation that the actions of antagonists such as MK-801 on cancer growth are specifically due to blockade of NMDA receptors will further their potential future use in cancer treatment. By confocal microscopy we were able to demonstrate that breast, ovarian, and prostate cancer cells express NMDA receptors within the membrane of tumor cells. Treating breast cancer cells with NMDA receptor antagonists and an antibody against an extracellular region of the subunit 1 changes the sub-cellular localization of these NMDA receptors. This change in sub-cellular localization could be an indicator of the mechanism of action of these compounds on cancer cell growth through the expression levels of the receptors. Additional studies are now being performed using sub-cellular fractionation and fluorescent microscopy to determine the nature of NMDAR1 cellular translocalization. The goal of this project is to further evaluate NMDA receptors as possible targets for treatment of breast cancer and perhaps several other cancer types. 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 3631. doi:10.1158/1538-7445.AM2011-3631
Abstract 1851: A role for heat-shock protein 40 YDJ1 in the protection from anthracycline exposure
Authors: Hernan Flores-Rozas, Tryphon Mazu
Journal: Cancer Research (2012)

Abstract Doxorubicin is an anthracycline antibiotic commonly used as an antineoplastic agent for the treatment of both solid tumors and hematological cancers. Although there is a dose-dependent response in the use of anthracyclines, there is also a dose-related toxicity associated to them, namely chronic cardiotoxicity. To increase our knowledge of the pathways that protect cells from the cytotoxic effects of anthracyclines, we carried out a genetic screening in the eukaryotic model organism S. cerevisiae, to identify gene defects that generate cells hypersensitive to doxorubicin. Our findings indicate that inactivation of the heat-shock protein 40 encoded by the genes YDJ1 and ZUO1, as well as the heat-shock protein 70 encoded by the gene SSZ1, render cells highly sensitive to the toxicity of doxorubicin. Further analysis of the YDJ1 defective strain revealed that it is also sensitive to daunorubicin and cisplatin, but not to other DNA damaging agents such as alkylating agents, the topoI inhibitor campthotecin or replication blocks from hydroxyurea. YDJ1 mutant displayed different sensitivity to DNA-double-strand breaks and oxidative damage, both of which are generated by anthracyclines. Complementation of the ydj1 mutation with the human DNAJA2 gene rescues the sensitivity of the deletion strain, suggesting a potential role of DNAJA2 in the protection to doxorubicin and implying that this mechanism also applies to higher eukaryotes. 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 1851. doi:1538-7445.AM2012-1851
Malignant Pleural Effusion Causing a Photon-Deficient Hemithorax
Authors: INA SAVITCH, K. JENNIE CHUN, LEONARD M. FREEMAN
Journal: Clinical Nuclear Medicine (2003)

From the Department of Nuclear Medicine, Montefiore Medical Center, and the Albert Einstein College of Medicine, Bronx, New York Received for publication July 10, 2002. Revision accepted November 14, 2002. Correspondence: Leonard M. Freeman, Department of Nuclear Medicine, Montefiore Medical Center, 111 East 210st Street, Bronx, New York 10467. E-mail: [email protected]
AB0566 Hospital anxiety and depression scale (hads) results in ankylosing spondylitis (as).
Authors: T. Doherty, N. Njegovan, V. Sandhu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Depression and anxiety are more prevalent in chronic diseases compared to the normal population<sup>1</sup>. In patients with ankylosing spondylitis (AS), unrecognised depression and/or anxiety is likely to lead to worse outcomes and suboptimal responses to AS treatments. Screening patients for anxiety and depression should improve our understanding of patients' disease and help to tailor AS treatments <h3>Objectives</h3> To assess the prevalence of anxiety and depression amongst AS patients and to correlate these conditions with patient reported outcomes. <h3>Methods</h3> In January 2012 we set up annual review clinics for patients with AS. Amongst screening for other comorbities we looked at Hospital Anxiety and Depression Scores (HADS-A and HADS-D respectively). We also looked at the BATH indices (BADAI, BASFI, BAS-G and Spinal Pain VAS), employment status, obesity, smoking and excess alcohol consumption and correlated these to HADS results. <h3>Results</h3> 59 patients attended (M=41, F=18) and completed HADS and BATH patient self assessments (BASDAI, BASFI, BAS-G, Spinal Pain VAS). 19 patiients had high anxiety scores (M=15, F=4) and 24 had high depression scores (M=17, F=7). 16 patients scored high on both anxiety and depression scales (M=12, F=4). High BASDAI scores were positively correlated with anxiety (p&lt;0.0001) and depression (p&lt;0.0007). Similarly BASFI (p&lt;0.002, p&lt;0.0002), BASS-G (p&lt;0.0005, p &lt; 0.00002) and Pain VAS (p&lt;0.002, p&lt;0.04) scores correlated with anxiety and depression. There was a correlation between and unemployment and depression (p&lt;0.04) but not with anxiety (p&gt;0.2). Obesity was also not correlated to anxiety but was to depression (p&lt;0.04). Smoking or alcohol excess were not linked to increased HADS. <h3>Conclusions</h3> Both anxiety and depression were prevalent in this patient group. Worse patient reported outcomes were noted in the presence of anxiety or depression. Recognising and treating anxiety and depression in AS is an important part of their management. Yearly review clinics are best suited to considering these chronic disease associations and discussing therapeutic options <h3>References</h3> Bayat N et al. Symptoms of anxiety and depression: A comparison among patients with different chronic conditions. J Res Med Sci. 2011 November; 16(11): 1441–1447 <h3>Disclosure of Interest</h3> None Declared
Abstract 4938: Extracellular miRNAs have potential as minimally-invasive biomarkers for predicting response to HER2-targeted agents, including Trastuzumab, as used in breast cancer
Authors: Claire Corcoran, Sweta Rani, Brigid Browne, John Crown, Norma O'Donovan, Lorraine O'Driscoll
Journal: Cancer Research (2011)

Abstract The identification of minimally-invasive biomarkers, in efforts to aid in patient-tailored disease management, has become a key focus of cancer research. Recent studies by ourselves and others have reported the existence of circulating miRNAs associated with breast cancer. Despite this progress, resistance to anti-cancer treatment remains a major obstacle in the treatment of this disease and unfortunately there are no reliable methods of predicting sensitivity/resistance to anti-cancer agents. This study aimed both to (i) identify miRNAs differentially-expressed in the breast cancer cell line SKBR3 and its Trastuzumab-resistant variant, SKBR3-H, developed by exposure to Trastuzumab for 6 months; and to (ii) investigate if corresponding differential levels of miRNAs were detectable in conditioned media (CM) from these cells, reflecting the relative sensitive/resistance profile of the SKBR3-H comparing to age-matched control SKBR3 cells. Global analysis of miRNAs was successfully performed on biological triplicate RNA specimens isolated from SKBR3 cells, SKBR3-H cells and on their respective CM, using TaqMan low density arrays representing 667 human miRNAs. 71.5% (477/667) miRNAs were detected in SKBR3; most (85%; 406/477) of which were detected in its CM. For SKBR3-H, 75.7% (505/667) miRNA analyzed were present in the cells, with 70% (354/505) of these also detected in corresponding CM. Of the 187 miRNAs up-regulated by at least 2-fold in SKBR3-H compared to SKBR3 cells, 6.42% (12/187) were up-regulated in corresponding CM. Of the 62 miRNAs down-regulated by at least 2 fold in SKBR3-H compared to SKBR3 cells, more than half (53.2%; 33/62) were down-regulated in corresponding CM. Several differentially regulated miRNAs were selected from TLDA results and subsequently validated in triplicate by qRT-PCR. Overall, the many hundred (∼500) miRNAs detected in CM further supports the existence of extracellular miRNAs and so their potential as minimally-invasive biomarkers. Furthermore, we identified a number of miRNAs that may help predict response to Trastuzumab. Our current research involves investigating the relative expression of miRNAs in SKBR3 variants resistant to other HER2-targeted agents and also examining the potential target genes for miRNAs identified as of most relevance here. Exploring the occurrence of these miRNAs in relevant patients’ serum specimens is now warranted to investigate clinical application. Acknowledgements: Science Foundation Ireland's SRC award to MTCI (08/SRC/B1410). 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 4938. doi:10.1158/1538-7445.AM2011-4938
Abstract 405: HTLV-1 infection of humanized SCID mice recapitulates adult T-cell leukemia/lymphoma (ATLL) development
Authors: Prabal Banerjee, Gerold Feuer, Lindsey Crawford, Michael Lairmore, Mark Beilke
Journal: Cancer Research (2010)

Abstract Human T-lymphotropic virus type-1 (HTLV-1) is the etiologic agent of Adult T-cell leukemia/lymphoma (ATLL), an aggressive CD4+/CD25+ T cell malignancy. The early molecular events induced by HTLV-1 infection as well as the role of various viral genes in the induction of leukemia remain unclear, predominantly due to the lack of an animal model that recapitulates ATLL development. We have previously demonstrated that HTLV-1 is capable of infecting human hematopoietic progenitor and stem cells (CD34+ HP/HSCs) and that infection of CD34+ HPCs has dramatically different biological effects in comparison to infection of mature T lymphocytes. To determine if HTLV-1 infection of CD34+ HP/HSCs recapitulates leukemogenesis in vivo, human hematopoiesis was reconstituted in NOD/SCID mice by injection of human CD34+ HPCs infected ex vivo with HTLV-1. Humanized NOD/SCID (HU-SCID) mice infected with HTLV-1 (HTLV-1-HU-SCID) consistently developed CD4+CD25+ T cell lymphomas with clinical characteristics associated with ATLL at ∼10 weeks post-reconstitution and show significantly elevated levels of HTLV-1 infected human CD4+ T cells in the thymus, mesenteric lymph node, spleen and peripheral blood. Lymphoma cells successfully engrafted in naïve NOD/SCID mice when injected into the peritoneal cavity and maintain the expression of viral proteins, gp46env and p19gag. Moreover these infected mice showed hyperproliferation of infected human stem cells (CD34+CD38−) in the bone marrow suggesting that HP/HSCs represents viral reservoir target cells which maintain HTLV-1 infection for extended periods of time in vivo. We speculate that HTLV-1 infection of hematopoietic stem cells establishes a virally-infected “cancer stem cell” which subsequently gives rise ATL in patients. Notably, CD34+ HPCs isolated from HTLV-1 infected patient PBL demonstrate proviral integrations, suggesting that these cells harbor infection in humans. CD34+ HPCs transduced with a lentivirus vector expressing the HTLV-1 Tax gene (Tax1) also results in CD4+/CD25+ T cell leukemia/lymphoma in HU-SCID mice, suggesting that Tax1 expression is sufficient for lymphomagenesis. HTLV-1 infection of humanized NOD/SCID mice represents a novel in vivo model which recapitulates viral lymphomagenesis and provides a compelling system to investigate and characterize molecular events in human stem cells in the initiation and progression to ATLL. 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 405.
AB1180 Subclinical temporo-mandibular joint (TMJ) involvement in juvenile idiopathic arthritis (JIA) detect by screening imaging
Authors: M. Gattinara, E. Del Giudice, S. Failoni, C. Mastaglio, C. Donati, I. Pontikaki, P.L. Meroni, V. Gerloni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Juvenile Idiopathic Arthritis (JIA) has been shown to involve the temporo-mandibular joint (TMJ) and the facial growth with a high frequency. Arthritis in this joint is often not associated with pain and clinical signs are usually poor <h3>Objectives</h3> To evaluate the validity of different TMJ screening methods we have studied 42 patients (32 female-10 male) mean age 15.1 yrs (range 6.8 -31.4), mean disease onset age 8.0 yrs (range 1-16) mean disease duration 6.6 yrs (range 0.1-21.4) <h3>Methods</h3> Our population included 42 consecutive cases of JIA without TMJ clinical symptoms (28 pauci, 9 poly, 2 systemic and 3 ERA HLA B27+). 28/42 patients (66%) showed an active disease with high flogistic indexes while in 14/42 (33%) the arthritis was inactive.23 patients were studied only with ultrasound imaging (US) of the TMJ, 9 cases performed only a MRI of the TMJ, while 10 patients have done the exams both.Finally 12 healthy subjects (7 female - 5 male) with a mean age of 11.3 yrs (range 5.0-21.0) were included in the study. 7 subjects performed only an US while 1 was investigated only with MRI. In 4 cases US and MRI were done together. The parameters calculated in both investigation were a) axial and coronal capsular and synovial thickening, b) erosions, c) synovial effusion, d) disc morphology and e) condylar translation movement <h3>Results</h3> Condylar translation was significantly reduced (p&lt;0.05) in JIA pts (mean 7.60 range 0.1-12 SD 3.1) vs controls (mean 8.76 range 4-10.7 SD 2.2), axial capsular thickening was significantly increase (p&lt;0.01) in JIA (mean 1.29 range 0.6-3.4 SD 0.5) vs control (mean 1.20 range 0.5-2.4 SD 0.5) and in the same way, coronal thickening was significantly (p&lt;0.001) increased in JIA (mean 1.32 range 0.5-3.5 SD 0.5) vs control (mean 1.25 range 0.5-2.3 SD 0.4).Using MRI erosions were seen in 22/38 joints of 19 pts (58%)in the coronal section and in 18/38 joints (47%) in the axial section while normal condylar profile was seen only in 7/38 joints (18%) using both sections <h3>Conclusions</h3> In conclusion US and MRI seems to be useful exams to investigate TMJ involvment in JIA showing an high rate of abnormality also in asymptomatic pts <h3>Disclosure of Interest</h3> None Declared