tbuckley/cabot-search huggingface dataset:
Abstract 609: Frondoside antagonizes the prostaglandin E receptor EP4 and inhibits breast tumor metastasis
Authors: Xinrong Ma, Namita Kundu, Peter Collin, Amy M. Fulton
Journal: Cancer Research (2011)

Abstract Sea cucumber has been used as a folk medicine for many conditions and recently antitumor activities have been described. Frondoside A, a triterpenoid glycoside isolated from the sea cucumber Cucumaria frondosa, as well as the related compound Frondanol A5 inhibit growth of pancreatic, colon and breast tumor cell lines in vitro and show activity in a primary prevention model of colon cancer. The cyclooxygenase 2 pathway contributes to growth and progression of many solid tumors by multiple mechanisms. The COX-2 product, prostaglandin E2 (PGE2) contributes to malignancy by acting on a family of four G-protein-coupled receptors (EP1, EP2, EP3, EP4). We have shown that both human and murine breast tumor cell lines express all EP receptors and that EP4 contributes to metastatic potential in a syngeneic murine model of metastatic breast cancer. Other laboratories have also provided evidence that EP4 promotes malignancy but a paucity of effective EP4 antagonists has slowed the development of clinically evaluable EP-targeted compounds. Based on the reported anti-inflammatory properties of Frondoside A, we asked if this compound has EP antagonist properties. We now report the novel finding that Frondoside A is a potent antagonist of EP4 and, to a lesser degree, antagonizes EP2. Frondoside A inhibits the binding of radio-labeled PGE2 to Chem-1 cells expressing EP4 or HEK cells transduced to express EP2. Using EP4-expressing MDA-MD-231 human breast cancer or murine mammary tumor cell line 66.1, we show that EP4-mediated activation of adenylate cyclase is also blocked by Frondoside A indicating both pharmacologic and functional EP4 receptor antagonism. We determined the effect of Frondoside A on metastatic potential of line 66.1 tumor cells. Treatment of 66.1 cells with non-cytotoxic concentrations of Frondoside A prior to i.v. administration of tumor cells into syngeneic Balb/cByJ female mice reduced lung colonizing capacity by 58%. These studies describe a potent metastasis inhibitory activity of Frondoside A and show, for the first time, that this compound may be a potent novel EP4/EP2 antagonist with activity in a model of metastatic breast cancer. 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 609. doi:10.1158/1538-7445.AM2011-609
Abstract P3-11-02: Aspirin Use in the Community and the Risk of Breast Cancer
Authors: C McCowan, S Carroll, B Makubate, JA Dewar, S Schweiger, AM. Thompson
Journal: Cancer Research (2010)

Abstract Introduction: Breast cancer is the most common cancer in women with incidence rates increasing annually. Laboratory work at Dundee had suggested aspirin may be a chemo-preventive agent for breast cancer, although a recent US study has shown no effect of aspirin use in reducing breast cancer in premenopausal women.1 Using routine population datasets in Tayside, this study examined the use of aspirin and the development of breast cancer. Methods: From the cancer registry all women in Tayside with an incident breast cancer from 1998 onwards were identified. Prescribing records for all women aged 30 and over were extracted for the period 1993 to 2003. Women with a breast cancer diagnosis prior to 1998 were excluded. Use of aspirin was examined with dosing and duration of use calculated. Cox proportional hazards models were used to determine if drug use reduced the risk of breast cancer Results: There were 117,948 women aged 30 or over on the 1st January 1998 who were resident throughout the study period or until their death. 1,761 had a diagnosis of breast cancer prior to 1st January 1998 and so were excluded from further analysis. There were 23,970 (20%) women who encashed a prescription for aspirin between 1st January 1993 and 31st December 2003. The median duration of aspirin use was 3.1 years (IQR 0.6-6.2) and patients took aspirin for a median 6 days (IQR 5-7) per week over that period. There were a total of 1,420 (1.2%) cancers recorded during the study period. Ever use of aspirin was associated with a reduced risk of breast cancer (HR=0.635, 95% CI 0.550-0.733, P&amp;lt;0.001) after allowing for age and social. Increasing duration of aspirin was associated with reducing risk of cancer compared to never users and higher aspirin usage was also associated with a decreasing risk. Conclusions: Aspirin would seem to be an effective chemo-preventive agent from this population based study. However further research is required to determine its effectiveness and to identify the groups of patients who may benefit the most from its use. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-02.
P270 MICRO RNA-27B CAUSES NONALCOHOLIC STEATOHEPATITIS SIMILAR TO HUMAN PATHOPHYSIOLOGY IN MURINE HIGH-FAT DIET MODEL
Authors: T. Kessoku, E. Sakai, Y. Honda, Y. Ogawa, W. Tomeno, K. Imajo, H. Mawatari, M. Yoneda, H. Kirikoshi, S. Saito, S. Maeda, Y. Eguchi, H. Mizuguchi, K. Wada, A. Nakajima
Journal: Journal of Hepatology (2014)
Protective and Damaging Effects of Stress Mediators
Authors: Bruce S. McEwen
Journal: New England Journal of Medicine (1998)

Over 60 years ago, Selye1 recognized the paradox that the physiologic systems activated by stress can not only protect and restore but also damage the body. What links these seemingly contradictory roles? How does stress influence the pathogenesis of disease, and what accounts for the variation in vulnerability to stress-related diseases among people with similar life experiences? How can stress-induced damage be quantified? These and many other questions still challenge investigators.This article reviews the long-term effect of the physiologic response to stress, which I refer to as allostatic load.2 Allostasis — the ability to achieve stability through change3 — . . .
The use of a mixed reality breast simulator with an innovative touch map feedback system to teach breast history-taking and examination skills.
Authors: AM Deladisma, A Kotranza, H Shah, P Fox, B Rossen, T Imam, S Wang, A Gucwa, C Pugh, B Lok, DS Lind
Journal: Cancer Research (2009)

Abstract Abstract #2105 Introduction: Physical examination remains an important method of breast cancer detection. Unfortunately, many health care professionals express concerns about missing breast lesions and current methods of teaching this essential skill are limited. Through an interdisciplinary collaboration, we created an immersive virtual patient to teach health professions students history-taking and breast examination skills.&amp;#x2028; Methods: Fifteen physician's assistant (PA) and 13 medical students (MS) interacted with a mixed reality human (MRH, a computer avatar with a mannequin-based breast simulator) with a breast complaint (Figure 1).&amp;#x2028; &amp;#x2028; Students spoke to and touched the MRH to take a history and examine a simulated breast with two masses of differing size and consistency. Subjects were surveyed regarding the usefulness of the virtual teaching tool and composed a patient note documenting pertinent history and physical examination findings. Students received feedback regarding the content of their patient note (number of 17 essential content items documented) and on the completeness of their breast examination (percentage area covered) using a color-coded touch map.&amp;#x2028; Results: Student feedback related to the utility of this virtual educational tool was positive. Students only documented a mean of 7.8±2.7 (range=4-15) essential content items in the breast history. The completeness of the breast exam was a mean of 82% (range=62% to 97%) of total breast area examined (Figure 2, green=area examined, red=area missed).&amp;#x2028; &amp;#x2028; More clinically experienced students (MS 3 and 4, N=9) performed better than those with no clinical experience (MS 1 and PA 1, N=19) in both history-taking (58% vs. 40%, p&amp;lt;0.05) and completeness of exam (90% vs. 84%, p&amp;lt;0.05). Fifty percent of students were able to locate at least one mass but only 14% were able to correctly document the location of both lesions.&amp;#x2028; Conclusions: The simulated experience differentiated performance among students with varying levels of clinical experience and identified a need for improved teaching and greater practice among all students. MRH scenarios provide a less anxious learning environment for students to practice breast history-taking and examination. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2105.
Abstract 3978: DDX20, a suppressor of hepatocarcinogenesis, controls NF-κB activity through regulating the function of miRNA-22 and miRNA-140-3p targeting transcriptional coactivators
Authors: Akemi Takata, Motoyuki Otsuka, Kentaro Kojima, Takeshi Yoshikawa, Takahiro Kishikawa, Hideaki Ijichi, Yoshihiro Hirata, Keisuke Tateishi, Haruhiko Yoshida, Masao Omata, Kazuhiko Koike
Journal: Cancer Research (2011)

Abstract MiRNA expression profile of human cancers has been characterized by an overall miRNA downregulation. While the causes include a transcriptional silencing and a failure of miRNA maturation, another possibility is that the deregulation of the machinery components for executing miRNA function also may cause similar consequences. Then, we screened the protein expression levels of the established members of the miRNA-containing ribonucleoproteins (Dicer, Ago2, TRBP2, DDX20 also known as Gemin3, and Gemin4) in various organ cancers by immunohisotchemistry. We detected reduced expression of DDX20 only in hepatocellular carcinoma tissues, while the levels of other genes were not drastically changed. We show that DDX20 suppresses NF-κB activity through regulating a subset of miRNA function. A microRNA library screen revealed that miR-140-3p and miR-22 suppress NF-κB activation by targeting the expression of NRIP1 and NCOA1, both are coactivators of NF-κB. However, in DDX20 deficient cells, this suppressive effect was lost, leading to NF-κB activation, a key regulator of hepatocarcinogenesis. In addition, DDX20 knockdown indeed induced cell transformation, revealed by a sphere-forming assay. These results indicate that DDX20 deficiency enhances NF-κB activity by impairing the NF-κB-suppressive action of microRNAs, and suggest that deregulation of the microRNA machinery may be one of the mechanisms of oncogenesis in liver cancers. 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 3978. doi:10.1158/1538-7445.AM2011-3978
AB1400 Physiotherapy in the recovery of quality of life in patients with acute lumbar facet
Authors: L.L. Vicas, F. Cioara, C. Nistor-Cseppento
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pain in the lumbar spine is present on at least 65% of patients that addresses a rehabilitation service. <h3>Objectives</h3> The objective of this study was to assess the recovery of back pain syndromes, pain and inflammation caused by decompensation of the lumbar spine facet joints by means of specific treatment balneofiziokinetoterapy <h3>Methods</h3> This study was conducted on a group of 58 patients with a mean age of 48.34 years, with lumbar facet syndrome diagnosis. The treatment was performed in Baile Felix, Oradea, Romania resort. The patient lot was processed aiming at the frequency data by age and sex, the predominant type of physical activity and associated diseases. All patients were investigated by medical imaging. We evaluated the influence of pain on the daily activities using the Quebec scale. The muscle strength was evaluated by Shirado and Sorensen Biering tests and quality of life using the Nottingham scale. Recovery program was to balneo-kineto-therapy, kinesiology at the gym, electro and masotherapy, every six months and in physical therapy at home. For quantitative comparison of mean values of the variables we used the T-student test. We calculated correlations between quantitative variables ranges of values using Pearson correlation coefficient. The statistical significance of the tests was set to 95% (<i>p=0.05</i>) <h3>Results</h3> We present here the statistically significant results. The presence of lumbar facet syndrome before the age of 45 years frequently accompanies a sedentary lifestyle and ligament laxity. Over 45 years, association with obesity is more common with static spinal disorders. Making systematic exercise programs significantly reduced back pain and therefore the number of episodes of pain relievers and NSAIDs consumption. Pain was improved in 86.20% of cases. Joint mobility was significantly improved in 89.20% and muscle strength improved in 79.31% of cases. Quality of life improved from an average of 32 points to 9 points. <h3>Conclusions</h3> Physical medicine therapeutic methods are effective for pain control to maintain stability and motility properties of the spine. The patient compliance for hygiene is important for joint restoration, preservation and improvement of muscle balance. Thorough clinical examination the patient has often an emphasized therapeutic relevance, even in the presence of severe outcomes imaging examination <h3>References</h3> Andersson GB, et al. (1999). A comparison of osteopathic spinal manipulation with standard care for patients with low back pain. New England Journal of Medicine, 341(19): 1426-1431 Carragee EJ, Hannibal M (2004). Diagnostic evaluation of low back pain. Orthopedic Clinics of North America, 35(2004): 7-16 Koes B, Van Tulder M (2006). Low back pain (acute), search date November 2004. <h3>Disclosure of Interest</h3> None Declared
Circuit Focus in Early Seizure After Acute Subcortical Hemorrhage
Authors: M Takasawa, M Watanabe, T Hoshi, T Sasaki, M Nukata, O Iiji, Y Nikaido, N Kinoshita, T Nukata
Journal: Clinical Nuclear Medicine (2000)

A 65-year-old right-handed man experienced the sudden onset of sensory aphasia and weakness of the right side of his body. He was hospitalized 2 days later, and a computed tomographic scan revealed subcortical hemorrhage in the left parietotemporal cortex. Thirty minutes after admission, he had a focal seizure beginning on the right side of the face and spreading to the right arm and right leg, without loss of conciousness. Ictal Tc-99m HMPAO SPECT showed hyperemia surrounding the hematoma. Furthermore, this hyperperfusion extended to the ipsilateral basal ganglia and occipital lobe. In the 5 minutes after the first SPECT, the convulsions gradually dissipated. On a second SPECT obtained 7 days after admission, the hyperperfusion had disappeared.
FRI0013 Ese-1: a novel pro-inflammatory and catabolic factor in articular cartilage
Authors: J. Conde, M. Scotece, M. Otero, V. Lopez, J. J. Gomez-Reino, M. B. Goldring, O. Gualillo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Articular cartilage is a highly specialized connective tissue that lines bone surfaces and provides a low friction in the joint. In adult articular cartilage, chondrocytes are responsible for the turnover and maintenance of the structural and extracellular matrix. However, during cartilage degenerative diseases chondrocytes exhibit aberrant behaviour and several factors, including members of the ETS family of transcription factors, are known to regulate many different processes including inflammation. ESE-1 is a novel member of ETS transcription factor superfamily. It is expressed in inflammatory conditions and in cartilage and synovium from osteoarthritis (OA) and rheumatoid arthritis (RA) subjects. <h3>Objectives</h3> Despite the large body of work on ETS biology, much remains to be learned about the precise function of ESE-1 in cartilage. Thus, this work aimed to determine the possible biological action/s of ESE-1 in chondrocytes. First, we analyzed the effect of ESE-1 on the induction of several inflammatory factors such as lipocalin-2 (LCN2), nitric oxide (NO), etc, and next the signalling pathways involved in these processes. Furthermore, we investigated the impact of ESE-1 on the expression of the principal collagen type II degrading enzyme, MMP-13. <h3>Methods</h3> We overexpressed ESE-1 using a pCI vector in human and murine chondrocytes in order to determine the effect of ESE-1 on specific target genes. Expression of ESE-1- driven genes was determined by qRT-PCR and western blot analysis. Next, to gain further insights, we analyzed the expression of LCN2 and nitric oxide in murine chondrocytes from wild type and ESE-1 knockout mice. <h3>Results</h3> ESE-1 overexpression, when cells have been stimulated in the presence of IL-1, was able to significantly increase lipocalin-2 expression and nitric oxide synthase type II production and activity in chondrocytes through a mechanism that involves NF-κB and PI3kinase activation. In addition, ESE-1 overexpression increases IL-1-induced MMP-13 expression through NF-κB. Finally, we observed that LCN2 and NO are produced to a lesser extent in chondrocytes from ESE-1 knockout mice compared to wild type mice. <h3>Conclusions</h3> All together, these data suggest that ESE-1 exerts clearly catabolic functions in articular cartilage. <h3>Disclosure of Interest</h3> None Declared
ERCC-1 gene expression levels and outcome to FOLFOX chemotherapy in patients enrolled in CONFIRM1 and CONFIRM2
Authors: H. J. Lenz, W. Zhang, M. M. Shi, C. Jacques, J. C. Barrett, K. D. Danenberg, A. C. Hoffmann, T. Trarbach, G. Folprecht, G. Meinhardt, D. Yang
Journal: Journal of Clinical Oncology (2008)

4131 Background: ERCC-1 is a nucleotide excision repair gene associated with DNA repair of DNA adducts induced by platinum based chemotherapy. ERCC-1 mRNA levels have been shown to predict outcome in patients with NSCLC, gastric, bladder and ovarian cancer when treated with platinum based chemotherapy. We tested whether ERCC-1 gene expression is associated with outcome in patients with metastatic colon cancer treated with FOLFOX in first and second line treatment with or without PTK/ZK Methods: 191 formalin fixed paraffin embedded (FFPE) tumor samples from patients enrolled in CONFIRM 1 and CONFIRM2 were analyzed. 85 patients from CONFIRM1 (42 pts treated with FOLFOX, 43 pts with FOLFOX/PTK/ZK) and 106 from CONFIRM2 (54 pts treated with FOLFOX, 52 with FOLFOX/PTK/ZK). FFPE tissues were dissected using laser-captured microdissection and analyzed for ERCC-1 mRNA expression using a quantitative real-time RT-PCR method. Gene expression values (relative mRNA levels) are expressed as ratios between the target gene and internal reference gene (beta-actin). Results: Low ERCC-1 gene expression was associated with better response to FOLFOX chemotherapy in first and second line chemotherapy (p=0.047, p=0.054). ERCC-1 gene expression was associated with overall survival in first and second line FOLFOX chemotherapy (p=0.014, p=0.14). pts with high ERCC-1 did not have any benefit from FOLFOX chemotherapy, but had benefit from treatment of FOLFOX+PTK/ZK, this drug and ERCC1 expression interaction was statistically significant (p=0.015). Conclusions: These results suggest that ERCC-1 gene expression levels predict response and overall survival in patients with metastatic colorectal cancer enrolled in CONFIRM1 and 2. ERCC-1 gene expression levels may allow the selection of patients who benefit likely from FOLFOX chemotherapy. We could show for the first time that VEGFR TKI efficacy may depend on ERCC-1 status. Further studies are warranted to study this unexpected interaction. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Novartis, Response Genetics, Inc Bristol-Myers Squibb, Genentech, ImClone, Merck, Pfizer, Response Genetics, Inc Novartis, Response Genetics, Inc Genentech, Merck, Pfizer, Roche, sanofi-aventis Dhont Family Foundation, NCI, NIH, Novartis
A1.37 Effects of four different treatment regimens on radiologic progression in early rheumatoid arthritis (RA)
Authors: E Fedorenko, G Lukina, Y Sigidin, D Karateev, A Smirnov, E Nasonov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Joint damage is especially rapid during early phases of RA and a key outcome measure in this disease. Therefore it is very important to assess effect of different treatment regimens on radiographic progression in early RA. <h3>Objectives</h3> To compare effect of 4 treatment regimens on the progression of joint destruction in patients (pts) with early RA. <h3>Methods</h3> One hundred forty-one pts with RA of less than two years9 duration (122 women, mean age 51 years, mean disease duration 24 weeks, mean DAS28 5,9; 64% RF-positive, 59% ACCP-positive) were randomised to receive one of the following treatment regimens: methotrexate (MTX, up to 20 mg/week, 35 pts); MTX plus prednisolone 10 mg daily (MTX-P, 34 pts); MTX-P plus methylprednisolone 1000mg intravenously on the first day of treatment (MTX-P-MP, 35 pts); leflunomide 20 mg daily (Lef, 37 pts). Duration of treatment was one year. Radiographs of hands and feet were scored using the Sharp–van der Heijde scoring method. <h3>Results</h3> At baseline all groups were comparable in their demographic, clinical and radiographic characteristics. One hundred twenty-seven pts completed the study. At 12 months there was no radiographic progression in the majority of pts (&gt;75% in each group). Increase of the number of erosions and joint space narrowings was maximal in MTX group (mean, 35 and 80 respectively), and minimal in MTX-P group (mean, 12 and 20 respectively), p = 0.066. Slowing of disease progression with Lef was similar to MTX. There were no significant differences in radiological score between groups MTX-P and MTX-P-MP at 12 months Relative slowing of disease progression was noted in groups MTX-P and MTX-P-MP in comparison with MTX group (p = 0.08) but not with Lef group (p&gt;0,1). Of note, among 20 pts with evident radiographic joint progression 9 pts had good clinical response according to EULAR criteria. RF and ACCP had no predictive value for the radiologic progression. <h3>Conclusion</h3> All 4 treatment regimens led to the slowing of joint destruction in the greater part of patients with early RA. In a portion of patients no correlation was found between clinical response and radiographic changes. Effects of MTX and Lef did not differ. High dose of Met at the start of treatment had no significant impact on the final results. Low dose of prednisolone given in addition to MTX substantially reduced radiologically detected progression of disease.
Ga-67 Activity in the Interposed Free Jejunum Mimicking Malignant Lesions
Authors: HITOYA OHTA, MASAHARU NAKADE, HIROYOSHI WATANABE, KEIJIRO KOHNO
Journal: Clinical Nuclear Medicine (1998)

Ga-67 imaging in a 52-year-old man with lung cancer showed intense uptake in the upper mediastinum. The patient had had an esophagogastrostomy with interposition of free jejunum for esophageal cancer 5 years earlier. Ga-67 activity in the interposed free jejunum was found to be responsible for the abnormal uptake in the upper mediastinum.
Elastic Stockings in the Prevention of Pulmonary Embolism
Authors: Robert W. Wilkins, George Mixter, Joseph R. Stanton, Julius Litter
Journal: New England Journal of Medicine (1952)

IT IS now generally recognized that pulmonary embolism most commonly arises from clinically silent phlebothrombosis in the deep veins of the leg.1 2 3 4 In their classic paper on this subject, Hunter and his co-workers4 state: "We are of the opinion that the greatest single factor favoring thrombus formation in the lower extremity is sudden confinement to bed of a previously ambulatory older person without the benefit of active exercise or the aid of gravity in the maintenance of an efficient venous circulation."Recently radiologic and anatomic studies in this laboratory have demonstrated that aneurysmal enlargements and saccular dilatations often occur in . . .