tbuckley/cabot-search huggingface dataset:
Biology and management of ependymomas
Authors: Jing Wu, Terri S. Armstrong, Mark R. Gilbert
Journal: Neuro-Oncology (2016)

Ependymomas are rare primary tumors of the central nervous system in children and adults that comprise histologically similar but genetically distinct subgroups. The tumor biology is typically more associated with the site of origin rather than being age-specific. Genetically distinct subgroups have been identified by genomic studies based on locations in classic grade II and III ependymomas. They are supratentorial ependymomas with C11orf95-RELA fusion or YAP1 fusion, infratentorial ependymomas with or without a hypermethylated phenotype (CIMP), and spinal cord ependymomas. Myxopapillary ependymomas and subependymomas have different biology than ependymomas with typical WHO grade II or III histology. Surgery and radiotherapy are the mainstays of treatment, while the role of chemotherapy has not yet been established. An in-depth understanding of tumor biology, developing reliable animal models that accurately reflect tumor molecule features, and high throughput drug screening are essential for developing new therapies. Collaborative efforts between scientists, physicians, and advocacy groups will enhance the translation of laboratory findings into clinical trials. Improvements in disease control underscore the need to incorporate assessment and management of patients' symptoms to ensure that treatment advances translate into improvement in quality of life.
THU0329 OPG/RANK/RANKL in pathogenesis of osteoporosis of juvenile idiopathic arthritis (JIA) subtypes
Authors: N. Abdel-Wahab, T.M. Khedr, E.A. Alkady, E. Mosad, S. Rashad
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> A decrease in bone mass has been described in a high percentage with increased risk of osteoporosis in JIA subtypes. The pathogenesis of bone loss in active JIA is complex, and results in reduced bone mineral density. Recent data have indicated an overlapping pathway between bone biology and biology of inflammation giving impression that inflammation may have a role in pathology of osteoporosis. Understanding the role of OPG/RANK/RANKL modulation in pathogenesis of bone loss among JIA subtypes will hold the key for identification of patients at risk and for management of osteoporosis. <h3>Objectives</h3> To evaluate the role of receptor activation of nuclear factor kB (RANK)/receptor activator of nuclear factor kB ligand (RANKL)/osteoprotegerin (OPG) modulation in juvenile idiopathic arthritis (JIA) subtypes with and without bone erosions. <h3>Methods</h3> Seventy children presenting JIA subtypes were recruited for the study and were chosen according to ILAR, 2001 criteria. They were compared with thirty healthy controls of matched age, sex, and ethnicity. Both groups had the average dietary intake of calcium products and sun exposure. Clinical presentations, laboratory investigations, and treatments used especially corticosteroids were recorded. JIA subtypes were oligo articular, polyarticular RF negative, RF positive, systemic onset JIA (SOJIA), enthesitis related arthritis (ERA) and psoriatic (PsA). All involved articulations were assessed by plain radiography for juxtaarticular osteoporosis and bone erosions. Disease activity was measured by Juvenile Arthritis Disease Activity Score (JADAS-27). Serum levels of OPG, RANK and RANKL were measured with estimation of OPG/RANKL ratio, using an enzyme-linked immunosorbent assay (ELISA). <h3>Results</h3> A significant low serum concentration of OPG was found in all JIA subgroups. There was a significant increase in serum level of RANKL, and a significant decrease of OPG/RANKL ratio. OPG/RANKL ratio was significantly lower in SOJIA, active polyarticular JIA and ERA than other groups within the subtypes. A significant low OPG/RANKL ratio was found in patients with prolonged steroid use and those with erosions. To our knowledge, this research is the first one studied these biomarkers in JIA subtypes, including ERA. <h3>Conclusions</h3> OPG/RANKL ratio can be an early predictor of increased bone resorption, and may be a valuable biomarker for bone damage in JIA subtypes. Systemic onset juvenile idiopathic arthritis, active polyarticular juvenile idiopathic arthritis and enthesitis related arthritis are at higher risk for osteoporosis. <h3>Disclosure of Interest</h3> None Declared
Excessively High Cell Proliferation in Sigmoid Colon After an Oral Purge With Anthraquinone Glycosides
Authors: J H Kleibeuker, A Cats, N Zwart, N H Mulder, M J Hardonk, E G de Vries
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Excessively High Cell Proliferation in Sigmoid Colon After an Oral Purge With Anthraquinone Glycosides Get access Jan H. Kleibeuker, Jan H. Kleibeuker Search for other works by this author on: Oxford Academic PubMed Google Scholar Annemieke Cats, Annemieke Cats Search for other works by this author on: Oxford Academic PubMed Google Scholar Nynke Zwart, Nynke Zwart Search for other works by this author on: Oxford Academic PubMed Google Scholar Nanno H. Mulder, Nanno H. Mulder Search for other works by this author on: Oxford Academic PubMed Google Scholar Machiel J. Hardonk, Machiel J. Hardonk Search for other works by this author on: Oxford Academic PubMed Google Scholar Elisabeth G. E. de Vries Elisabeth G. E. de Vries Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 6, 15 March 1995, Pages 452–455, https://doi.org/10.1093/jnci/87.6.452 Published: 15 March 1995 Article history Received: 15 June 1994 Revision received: 14 November 1994 Accepted: 27 December 1994 Published: 15 March 1995
Abstract 404: Proinflammatory cytokine IL-1β stimulates IL-8 synthesis in mast cells via a leukotriene B4 receptor 2-linked pathway, contributing to angiogenesis
Authors: Jin-Wook Lee, Hyunju Kim, Jun-Dong Wei, Ji-Min Seo, Soo Young Park, Geun-Soo Park, A-Jin Lee, Jae-Hong Kim
Journal: Cancer Research (2011)

Abstract Recent studies have suggested that mast cells have critical roles in angiogenesis. However, the detailed mechanism by which mast cells contribute to angiogenesis is not yet clearly understood, especially in response to proinflammatory cytokines. In this study, we showed that the proinflammatory cytokine IL-1β induces the synthesis of IL-8, a potent angiogenic factor, in human mast cells via the leukotriene B4 receptor (BLT)2. We also characterized the BLT2 downstream signaling pathway and determined that BLT2-mediated IL-8 synthesis involves the upregulation of Nox1, a member of the NADPH oxidase family, Nox1-dependent reactive oxygen species generation and the subsequent activation of the redox-sensitive transcription factor NF-κB. For instance, knockdown of BLT2 and Nox1 with specific small interfering RNA, treatment with a specific BLT2 antagonist, LY255283, or treatment with a potential Nox inhibitor, diphenylene iodonium, suppressed IL-1β-induced IL-8 synthesis. We found that the conditioned media collected from IL-1β-treated human mast cell line HMC-1 had significantly enhanced angiogenic activity that could be dramatically attenuated by either small interfering RNA knockdown of BLT2 or treatment with neutralizing Ab to IL-8. Finally, the experiments were repeated using human primary cord blood-derived mast cells, and the results were clearly reproduced. Taken together, our results suggest that BLT2-Nox1-reactive oxygen species-dependent pathway plays a role in promoting the secretion of IL-8 from human mast cells in response to the proinflammatory cytokine IL-1β, thus contributing to angiogenesis. 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 404. doi:10.1158/1538-7445.AM2011-404
PARE0021 Challenging Mental Health Disorder in Long Term Rheumatic Disease Clinics
Authors: C. Lim, J. Kirk, E. Edwards, B. Colaco
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The prevalence of mental health disorder in individuals with Rheumatic disease is higher than that of the general population<sup>1,2</sup>. An audit of 240 patients attending general and specialist Rheumatology clinics at Central Middlesex Hospital (CMH) found a 50% reported rate of Anxiety or Depression on a HADS questionnaire, and a 50% reduced experience of Quality of Life. The CMH Rheumatology Support Group (CMH RSG) monthly discussions also highlight depression and anxiety amongst its members. <h3>Objectives</h3> The objective of the initial National Association of Mental Health (MIND) meeting was to provide information on what MIND does, and how patients may access their voluntary care which is approved by state-run Mental Health services and works in collaboration with GPs. <h3>Methods</h3> JK contacted the MIND charity who provided a representative to give an introductory talk to over 50 CMH RSG members. <h3>Results</h3> This meeting provoked a need to start our own CMH RSG MIND group. We started with 6 members in November 2013 and the group, named "Positive Thoughts" now has the maximum 12 members. We have another 8 members on the waiting list for the second phase. <h3>Conclusions</h3> Depression and anxiety is common in patients with long term rheumatic disease and can influence morbidity, disease progression and outcome. Self-help Patient groups can contribute to positive outcomes. A service dedicated to looking after the mental well-being of patients is vital to any Rheumatology department <h3>References</h3> Sheehy C, Murphy EM, Barry M. Depression in rheumatoid arthritis-underscoring the problem. Rheumatology 2006;45:1325-1327 Uguz F, Akman C, Kucuksarac S, Tufekci O: Anti tumor necrosis factor therapy is associated with less frequent mood and anxiety disorders in patients with rheumatoid arthritis. Psychiatry Clin Neurosci 2009; 63:50-55 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5297
Comparison of Tc-99m Pertechnetate With Tl-201 and Ga-67 Scintigraphy of Malignant Soft-Tissue Tumors
Authors: HIROYUKI ABE, SHOJI TERUI, TAKASHI TERAUCHI, YUKIO MURAMATSU, RYOUHEI YOKAYAMA, KATSUYUKI OHTOMO, YASUO BEPPU, HISATOSHI FUKUMA
Journal: Clinical Nuclear Medicine (1997)

Tc-99m pertechnetate scintigraphy was compared with Tl-201 chloride and Ga-67 citrate to evaluate the avidity of Tc-99m pertechtate for malignant soft-tissue tumors. Twenty-three patients with malignant soft-tissue tumors underwent scintigraphic studies. All 23 received Tc-99m and Tl-201, whereas 14 also were injected with Ga-67. In 21 (91%) of the 23 patients, Tc-99m accumulated extensively in the tumors. Tl-201 accumulated in 12 (52%) of the 23 tumors. Ga-67 accumulated in only 5 (36%) of the 14 tumors. The avidity of Tc-99m for myxoid tumors was markedly different from the other two agents. Tc-99m accumulated in all eight myxoid tumors, while neither Tl-201 or Ga-67 showed marked accumulation except for one patient with increased accumulation of Tl-201. This study shows that Tc-99m pertechnetate has the potential to localize malignant soft-tissue tumors and may be useful in the evaluation of these tumors.
Recent Impressions of Medical Practice in Great Britain
Authors: William H. Sweet
Journal: New England Journal of Medicine (1949)

MANY physicians have hitherto regarded only with casual interest the controversy over the organization of medical practice in this country. I, myself, for example, have assumed that a faculty member of the staff of a teaching hospital could be little affected by any of the bruited changes—a notion that has been sharply challenged by observations of the current status of physicians in this and other categories in Great Britain. Severely jarred in my complacency by what I have seen during a recent period of work on one of the active services of a large English hospital, I am recording what . . .
THU0256 Effectiveness of autologous hematopoietic stem cell transplantation for interstitial lung diseases in patients with systemic sclerosis
Authors: T. Odani, S. Yasuda, M. Kono, T. Kurita, Y. Fujieda, K. Otomo, Y. Kon, T. Horita, T. Atsumi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Interstitial lung disease (ILD) is a major source of mortality in systemic sclerosis (SSc). Autologous hematopoietic stem cell transplantation (HSCT) is employed as a new therapeutic strategy in patients with severe/progressive form of SSc and its effectiveness for SSc-related ILD was reported (1, 2). <h3>Objectives</h3> To evaluate effect of HSCT for SSc-related ILD. <h3>Methods</h3> A total of 77 SSc patients were screened and evaluated for ILD, using high-resolution computed tomography (HRCT) and pulmonary function tests. Ten patients treated with HSCT and 30 patients treated with conventional therapy were evaluated retrospectively. In both groups, disease durations of the patients were less than 3 years at baseline. HSCT was performed as previously reported (3). Image findings were quantified according to HRCT score as reported (4). We evaluated ΔHRCT score from the baseline to 2 years' time-point, and compared those between HSCT group and conventional group. <h3>Results</h3> Baseline demographics such as sex, age, disease duration, the observation period, smoking history, the phenotype of SSc (limited or diffuse), the prevalence of ILD, autoantibodies, serum KL-6, respiratory function and HRCT findings including HRCT score, were not significantly different between two groups. HSCT group revealed significantly more improved ΔHRCT score than Conventional group at the observation periods (-0.1±2.8 vs. 1.3±1.8; p=0.018). No one died due to progression of SSc or transplantation in HSCT group, whereas three patients died due to exacerbation of lung disease or malignancy in Conventional group. <h3>Conclusions</h3> HSCT therapy improved the HRCT findings in SSc patients with ILD. <h3>References</h3> Tsukamoto H, et al. A phase I-II trial of autologous peripheral blood stem cell transplantation in the treatment of refractory autoimmune disease. Ann Rheum Dis. 2006; 65:508-14 Burt RK, et al. Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial. Lancet. 2011; 378:498-506 Bohgaki T et al., Immunological reconstitution after autologous hematopoietic stem cell transplantation in patients with systemic sclerosis: relationship between clinical benefits and intensity of immunosuppression. J Rheumatol. 2009;36:1240-8. Goldin JG, et al. High-resolution CT scan findings in patients with symptomatic scleroderma-related interstitial lung disease. Chest. 2008; 134:358-67. <h3>Disclosure of Interest</h3> None Declared
MHC genes determine fetal susceptibility in a rat model of congenital heart block
Authors: Vijole Dzikaite, Maja Jagodic, Vijay K Kuchroo, Tomas Olsson, Marie Wahren-Herlenius
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> Congenital heart block (CHB) develops in fetuses of anti-Ro52 antibody positive women. A recurrence rate of 12–25%, despite the persistance of maternal autoantibodies indicates that there are additional, yet unidentified, factors critical for development of CHB. The authors hypothesised that fetal susceptibility to the maternal autoantibodies could be determined by fetal genes. <h3>Methods</h3> A passive antibody transfer model was used in several different rat strains and MHC congenics (DA.AV1; Lew.1AV1; Lew.L; Lew.N). Two-four mg of a Ro52 monoclonal antibody (7.8C7) was injected intraperitonially before day 7 of gestation. On the day of delivery, three-lead ECG were recorded from conscious pups. <h3>Results</h3> After maternal passive antibody transfer, significant PR prolongation was induced in the DA.AV1 pups by Ro52-p200 specific antibodies at the dose of 4 mg. In Lew.1AV1 rats, PR prolongation was induced in the pups already at 2 mg injections, indicating that fetal non-MHC genes can increase susceptability to CHB. In Lew.L rats, PR intervals were significantly more prolonged after 2 mg injections, indicating that fetal L MHC genes conferred to highest susceptibility to CHB. In Lewis.N rats however, no difference in the PR intervals were observed between the PBS-injected control group and groups injected with 2 or 4 mg of Ro52 monoclonal antibody, suggesting that specific fetal MHC genes can confer the resistance and play a protective role in the development of the CHB. <h3>Conclusions</h3> Our findings show that both fetal MHC and non-MHC genes regulate susceptibility to CHB and determine the fetal disease outcome in anti-Ro52 positive pregnancies. Different fetal MHC alleles can either render the fetus susceptible or play a protective role in the disease development.
Abstract 2649: Whole body vibration effects on binding kinetics and targeting of near-infrared dye conjugated bisphosphonate
Authors: Rao V. Papineni, Sean Orton, William McLaughlin, Douglas Vizard, Tao Ji, Hans Schmitthenner, Jingyi Pan
Journal: Cancer Research (2010)

Abstract A non-invasive means of targeting bisphophonate to specific skeletal sites, along with the passive binding/decay kinetics of the near-infrared bisphosphanate analog to the skeleton are determined. Bone is the third common site where breast, lung, and prostate cancer cells spread and metastasize. Debilitating pain is the major complication resulting from bone metastases in nearly 70% of the patients. The palliative bone pain management includes the bisphosphanate therapy. Bisphosphonates, a potent inhibitor of bone resorption, gives both pain relief and improves bone health. However these medications result in complications such as bisphosphonate-related osteonecrosis of the jaw (BRONJ). Combinations of low-risk exercise programs along with reduced drug dosage are a likely alternative to counter such drug-related side effects. Site-selective skeletal targeting of bisphosphonates, if feasible, is however ideal to overcome drug-related side effects. We utilized whole body vibration (WBV), to target NIR dye conjugate bisphosphonate to specific skeletal sites. Using near-infrared (NIR) fluorescence imaging, both the targeting and the passive binding of the bisphosphonate in vivo was determined. Vibration loading, utilizing whole body vibration (WBV) was performed on twelve mice by subjecting them to vibration frequency of 35 Hz for fifteen min (5-10 times/week) duration. Alendronate was conjugated to near-infrared tricarbocyanine, cyclic enamine-functionalized dye, and was injected intravenously after 21-day exercise regime. Yet to be reported, we show that NIR-alendronate probe bound to the lumbar L6 vertebrae, resultant of direct high-frequency WBV stimulation. This is besides several other specific targeting sites. Further, both the passive binding and the decay kinetics of the NIR signal at the skeleton was determined in a six-week non-invasive longitudinal study of mouse pups. This provides opportunity to utilize such approaches in future translational studies in assessing the role of bisphosphonates in preventing spreading of cancer cells at other secondary sites, especially bone. The targeted drug binding in response to the vibratory protocol also provides hope in the development of whole body vibration (WBV) as a bisphosphonate-therapeutic aid. Further, to develop strategies in reducing the drug dosage in treatment of other morbidity factors that stem from complications from bone metastases. 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 2649.
Minding the dream self: Perspectives from the analysis of self-experience in dreams
Authors: Jennifer Michelle Windt
Journal: Behavioral and Brain Sciences (2013)

Abstract Can ancient art of memory (AAOM) principles explain the function of dreaming? The analysis of self-experience in dreams suggests that the answer is no: The phenomenal dream self lacks certain dimensions that are crucial for the efficacy of AAOM in wakefulness. However, the comparison between dreams and AAOM may be fruitful by suggesting new perspectives for the study of lucid dreaming as well an altered perspective on the efficacy of AAOM itself.
Abstract 2888: Vitamin D inhibits obesity-induced endometrial carcinogenesis in <i>Pten+/−</i> mice
Authors: Wei Yu, Larry G. Maxwell, Mark Cline, David Berrigan, Gustavo Rodriguez, Anni Warri, Leena Hilakivi-Clarke
Journal: Cancer Research (2010)

Abstract Objectives: A growing body of epidemiologic and experimental evidence suggests that vitamin D may lower the risk of a number of epithelial malignancies. In this study, we sought to determine whether vitamin D exposure reverses endometrial carcinogenesis in an animal model, and further whether it modifies the enhanced risk of endometrial carcinoma associated with obesity. Methods: When 4 weeks of age, Pten+/− and wildtype (WT) mice were each divided into four treatment groups and fed an AIN93G based diet containing either (1) 18% energy from fat (control diet), (2) 18% fat and 25K IU of VD3/kg diet (VD3 supplemented control diet), (3) 58% fat to induce obesity (obesity inducing diet, OID), and (4) 58% fat and 25K IU of VD3/kg diet (VD3 supplemented OID). Mice were kept on these diets until they were sacrificed at 28 weeks of age. Results: Dietary VD3 exposure did it cause any apparent toxicity. VD3 increased the expression of 25-hydroxylase (25-OHase, an enzyme converting VD3 to 25(OH)D3) in the endometrium of WT (p&amp;lt;0.027) and Pten+/− mice (p&amp;lt;0.025). Further, it increased vitamin D receptor (VDR) levels (p&amp;lt;0.006) in the obese Pten+/− mice. Although VD3 did not affect endometrial cancer risk, it inhibited obesity-induced increase in endometrial cancer. Specifically, OID increased focal glandular hyperplasia with atypia and malignant lesions from 58% in the control diet fed Pten+/− mice to 78%. Dietary VD3 supplementation decreased the incidence of endometrial pathology in Pten+/− mice fed OID to 25% (p&amp;lt;0.001). Estrogen receptor (ER)-α mRNA levels were significantly higher (p&amp;lt;0.014) and progesterone receptor (PR) protein levels in the luminal epithelium were significantly lower (p&amp;lt;0.04) in the endometrium of control diet fed Pten+/− mice than in the WT mice, but the expression of ER-α, ER-β or PR mRNA, or epithelial or stromal protein expression were not affected by the dietary exposures. Conclusions: Our data obtained in Pten+/− mice confirm the known association between increased body weight and endometrial cancer risk. Dietary exposure to VD3 inhibited the carcinogenic effect of obesity on the endometrium; the mechanism mediating this protective effect was not linked to changes in the expression of ER-α, ER-β or PR. 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 2888.