tbuckley/cabot-search huggingface dataset:
Abstract 3560: Application of metabolomics to assess serum profiles in limonene-treated breast cancer patients
Authors: Jessica A. Miller, Elizabeth J. Want, Patricia A. Thompson, Julie E. Lang, Peter Lance, H-H. Sherry Chow
Journal: Cancer Research (2012)

Abstract Background. Limonene is a highly lipophilic monoterpene found in citrus peel that has demonstrated anticancer effects in preclinical models. Limonene likely affects multiple targets with varying potency. Advanced techniques to obtain metabolomic profiles from biofluids have the potential to provide a non-invasive means to assess these multiple effects. This strategy was applied to a clinical trial with women with early stage breast cancer receiving limonene treatment. Methods. Forty women with stage 0 - 2 breast cancer received 2 g QD limonene daily for 2 - 6 weeks (21.5 + 8.8 days) before scheduled surgical resection of their tumor. Pre/post intervention blood draws were taken for metabolomics analysis. Metabolomics profiling was conducted using ultra performance liquid chromatography tandem time-of-flight mass spectrometry (UPLC-QToF). Chromatographic separation was achieved using a gradient of two mobile phases; A: 0.1% formic acid in water, and B: 0.1% formic acid in methanol with a flow rate of 0.4 mL/min. A Waters Aquity UltraPerformance LC HSS T3 column was used. Metabolomics data was preprocessed with XCMS. Preliminary metabolite identification was conducted by mining the Human Metabolome Database (HMDB). Results. Over 1,000 metabolite features were identified by metabolomic profiling. In negative ion mode, three metabolites exhibited a 48-fold change or higher from pre to post-intervention; 183.1 m/z at 9.4 min, 177.0 m/z at 10.0 min, and 345.1 m/z 8.9 min (P's&amp;lt;0.001). Two distinct peaks with m/z of 103.0 elute at 1.9 and 2.25 minutes respectively and changed &amp;gt;20% (P's&amp;lt;0.05). Twenty potential metabolites were identified in positive ion mode with &amp;gt;20% change by the intervention (P's&amp;lt; 0.05), of these, two exhibited 10-fold change or higher; 312.2 m/z at 8.7 min, and 369.2 m/z at 9.0 min (P's&amp;lt;0.001). Discussion. This study demonstrates that 2 g QD daily oral limonene results in significant changes in approximately 20 metabolites in serum. Candidate compounds include limonene metabolites, carnitines and end products of arachindonic acid metabolism. Efforts are ongoing to identify these metabolites for analyte specific verification and quantitation. Further clinical trials with limonene are necessary to establish its potential role as a chemopreventive agent in breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3560. doi:1538-7445.AM2012-3560
Mesoporous Silica Particles as a Multifunctional Delivery System for Pain Relief in Experimental Neuropathy
Authors: Junran Xie, Dongju Xiao, Jinning Zhao, Nianqiang Hu, Qi Bao, Li Jiang, Lina Yu
Journal: Advanced Healthcare Materials (2016)

The long‐term use of potent analgesics is often needed to treat chronic pain. However, it has been greatly hindered by their side effects such as addiction and withdrawal reactions. The study seeks to circumvent these drawbacks by taking advantage of a multifunctional delivery system based on nanoparticles to target on pathological neuroinflammation. A drug delivery system is designed and generated using mesoporous silica nanoparticles (MSNs) that are loaded with Δ9‐THC (Δ9‐tetrahydrocannabinol, a cannabinoid) and ARA290 (an erythropoietin‐derived polypeptide), both of which possess analgesic and anti‐inflammatory functions. The actions of such THC‐MSN‐ARA290 nanocomplexes depend on the enhanced permeability and retention of THC through nanosized carriers, and a redox‐sensitive release of conjugated ARA290 peptide into the local inflammatory milieu. The biosafety and anti‐inflammatory effects of the nanocomplexes are first evaluated in primary microglia in vitro, and further in a mouse model of chronic constriction injury. It is found that the nanocomplexes attenuate in vitro and in vivo inflammation, and achieve a sustained relief of neuropathic pain in injured animals induced by both thermal hyperalgesia and mechanical allodynia. Thus, a nanoparticle‐based carrier system can be useful for the amelioration of chronic neuropathic pain through combinatorial drug delivery.
Case 39-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Didier Cros, Nancy L. Harris, E. Tessa Hedley-Whyte
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 66-year-old man was admitted to the hospital because of progressive muscle weakness and paresthesias.The patient was in excellent health until two days before admission, when he mowed his lawn without difficulty; that evening he experienced mild pain in the back and thighs, with slight numbness of the soles of his feet and his fingers. On getting out of bed the next morning he found that his legs were weak, stiff, and painful, and his gait was unsteady. He was admitted to another hospital with a tentative diagnosis of lumbar-disk disease, but an emergency myelographic examination . . .
PTU-021 Eosinophilic Oesophagitis: Diagnostic Rates Can Be Improved By Education
Authors: A Davies, O Burdall, C Streets
Journal: Gut (2014)

<h3>Introduction</h3> Eosinophilic oesophagitis (EoE) is a chronic immune-mediated disease associated with oesophageal dysfunction, most commonly dysphagia. Recent consensus guidelines recommend obtaining biopsies from both the proximal and distal oesophagus in patients with dysphagia who have normal endoscopies.<sup>1</sup> This study aims to investigate the adherence to these guidelines and familiarise clinicians with this pathology. <h3>Methods</h3> The study included 2 cycles, each of 6 months. Cycle 1 was from 1/5/12 until 6/11/12. Cycle 2 extended from 1/1/13 until 6/7/13. For each cycle the hospital database was used to review the records of all patients that underwent endoscopies for dysphagia as the primary symptom. All normal endoscopies were included. The number of biopsies and histology results were recorded. Following the first cycle recommendations and information was displayed in all endoscopy rooms and the results fed back to the lead clinicians before cycle 2 was carried out. <h3>Results</h3> In Cycle 1, 258 patients underwent endoscopies for dysphagia with 75 considered endoscopically normal. In cycle 2, 263 endoscopies were carried out, of which 74 appeared normal. Biopsies were taken from 27% (n = 20) of the normal endoscopies in Cycle 1, with 5% (n = 1) of those biopsied proving histologically positive for EoE. This increased in Cycle 2 to 45% (n = 33) biopsied and EoE present in 12% (n = 4). <h3>Conclusion</h3> Eosinophilic oesophagitis is an important diagnosis that may result in complications if missed and not specifically treated. Oesophageal biopsies are underperformed in patients with normal endoscopies. An improvement in biopsy rates through education has increased the number of successful diagnoses at this Trust. However, continued improvement is required as clinicians need to be vigilant regarding this this pathology when developing a differential diagnosis for dysphagia. <h3>Reference</h3> Dellon ES, Gonsalves N, Hirano I, Furuta GT, Liacouras CA, Katzka DA. ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). <i>American Journal of Gastroenterology</i> 2013;108(5):679–692 <h3>Disclosure of Interest</h3> None Declared.
Stat Bite Impact of Combination Chemotherapy for Advanced Testicular Cancer
Authors: E. J. Feuer
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Stat Bite Impact of Combination Chemotherapy for Advanced Testicular Cancer Get access Eric J. Feuer, Ph.D. Eric J. Feuer, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 7, April 1992, Page 474, https://doi.org/10.1093/jnci/84.7.474 Published: 01 April 1992
PTH-195 Lubiprostone Treatment Improves Constipation and Related Symptoms in Patients Refractory to other Constipation Therapies
Authors: R M Panas, T Joswick, P Lichtlen, D Panigrahi, R Ueno
Journal: Gut (2013)

<h3>Introduction</h3> Constipation affects millions globally; however, many patients are dissatisfied with currently-available laxative treatments, with most interested in access to other treatment options<sup>1</sup>. Lubiprostone (24 mcg BID) has been shown to be effective and well-tolerated in patients with refractory constipation. <h3>Methods</h3> Post-hoc analysis was conducted to evaluate whether lubiprostone provides relief in patients who are refractory or lacking adequate relief from other common constipation therapies. Pooled patient and medication data from two pivotal trials were assessed. Patients with a history of constipation despite the use of constipation medication during the 90 days prior to initiation of study medication were included. Response rates and symptomatic improvements in this subpopulation of refractory patients were analysed based on treatment assignment in the clinical trial: lubiprostone (24 mcg BID) or placebo. Analysis was performed on the whole and by the class of prior medication usage. Patients were considered full responders if they achieved ≥4 spontaneous bowel movements (SBMs)/week. Patients achieving ≥3 but &lt; 4 SBMs/week were moderate responders; those with &lt; 3 SBMs/week were non-responders. Symptomatic improvements were also assessed. <h3>Results</h3> Full response to treatment ranged from 52.8 to 67.2% across the 4 weeks of treatment, as compared to 32.3% to 47.4% for placebo patients. For patients who were moderate responders, response rates increased to 64.8–80.0% among the lubiprostone treatment group compared to only 46.6–57.9% of placebo patients. Lubiprostone produced a significant and full response over placebo, respectively, among the refractory patients who previously took contact laxatives 50.9–64.9% vs. 21.3–42.6%; PEG solutions 57.5–75.0% vs. 32.5–52.5%; or enemas 50.0–71.4% vs. 23.3–50.0%. For symptoms of constipation such as stool consistency and straining, lubiprostone treatment resulted in statistically significant improvements compared to placebo at each study week (p≤0.001). In particular, lubiprostone statistically significantly improved overall stool consistency among patients who previously used contact laxatives (p≤0.001), enemas (p≤0.007) or PEG solutions (p≤0.003) at all treatment weeks. Statistically significant improvements in straining were seen at all treatment weeks in patients who previously used PEG solutions (p≤0.018). <h3>Conclusion</h3> Given the statistically significant response to lubiprostone in patients refractory to other constipation therapies, lubiprostone may be a helpful addition to the armamentarium for patients suffering from chronic idiopathic constipation. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> Müller-Lissner<i> et al.</i> Aliment Pharmacol Ther 2013; 37(1):137–145.
Serum Complement Levels in Bacteremia Due to Gram-Negative Organisms
Authors: William R. McCabe
Journal: New England Journal of Medicine (1973)

Mean (± S.D.) levels of C3 did not differ significantly between 75 control patients (141.4 ± 22 mg per 100 ml) and 68 patients with bacteremia due to gram-negative organisms(132 ± 50 mg per 100 ml). In the 41 patients with uncomplicated bacteremia the mean C3 levels (151 ± 51 mg per 100 ml) did not differ from values in controls; however, a significant reduction in C3 levels was observed in 26 patients with shock (105 ± 31 mg per 100 ml) and the 19 patients who died (98 ± 38 mg per 100 ml) of bacteremia (p less than 0.001). The frequency of occurrence of shock or fatal outcome tended to parallel the degree of lowering of C3 levels in serum specimens obtained shortly after the onset of bacteremia.
PWE-032 Endoscopic mucosal resection (EMR) followed by adjuvant radiofrequency ablation (RFA) can result in better outcomes compared to EMR alone in patients with Barrett's early neoplasia (EN). A comparative study from a tertiary centre in the UK: Abstract PWE-032 Table 1
Authors: S Sami, E Telakis, J Mannath, P Kaye, K Ragunath
Journal: Gut (2012)

<h3>Introduction</h3> RFA has shown efficacy in eradicating Barrett9s EN (high grade dysplasia (HGD) or intra-mucosal cancer (IMC)). To our knowledge, there are no studies directly comparing outcomes in patients with EN who undergo EMR alone vs EMR followed by RFA. The aim of this study was to assess the efficacy, safety and long term outcomes of adjuvant RFA in this setting. <h3>Methods</h3> We searched our prospective Barrett9s Oesophagus EMR database for patients who had EMR of lesions harbouring EN followed by RFA for eradication of residual Barrett9s mucosa between 2007 and 2008 as part of a multi-centre trial (intervention group). The control group included patients with similar lesions who had undergone EMR followed by surveillance of residual Barrett9s mucosa. The two groups were matched for any potential confounders to minimise bias. <h3>Results</h3> There were 13 patients in each group. Mean age in the EMR group and EMR+RFA group was 70 and 59 years, respectively. Both groups were equally matched in terms of male to female ration (12:1); length of circumferential Barrett9s mucosa; lesion Paris classification; mean lesion size; and resection type (Piecemeal or En-bloc). The mean duration of follow-up in the EMR group was 21 months compared to 32 months in the EMR+RFA group. The histological characteristics of lesions in both groups are shown in the table below (Abstract PWE-032 table.1). Overall, histological eradication of EN was achieved in eight (62%) patients in the EMR group and 13 (100%) in the EMR+RFA group at the last follow-up. Persistence or recurrence of EN and the need for further EMR during follow-up occurred in five patients (38%) in the EMR group (two of them had Oesophagectomy) compared to only one (8%) in the EMR+RFA group. One patient (8%) in the EMR group developed oesophageal stricture and no complications occurred in the other group. <h3>Conclusion</h3> These data suggest that adjuvant RFA in this setting can have a significant positive impact on the long term success rate of histological eradication of EN in Barrett9s Oesophagus as well as reducing the risk of recurrence of those lesions. It can reduce the need for subsequent EMRs and radical surgery with no safety concerns. The long duration of follow-up and control for confounders add significant validity to the results, despite the relatively small number of patients included. <h3>Competing interests</h3> S Sami: None declared, E Telakis: None declared, J Mannath: None declared, P Kaye: None declared, K Ragunath Grant/Research Support from: Olympus, Cook and Barrx medical.
Comparison of the L10M consolidation regimen to an alternative regimen including escalating methotrexate/L-asparaginase for adult acute lymphoblastic leukemia: a Southwest Oncology Group Study
Authors: SH Petersdorf, KJ Kopecky, DR Head, DH Boldt, SP Balcerzak, T Wun, V Roy, RW Veith, FR Appelbaum
Journal: Leukemia (2001)
292 PAN-CASPASE INHIBITION PROTECTS AGAINST FIBROTIC NASH INDUCED BY CHOLINE DEFICIENT AMINO ACID DEFINED DIET (CDAA)
Authors: W. Lu, A. Eguchi, D. Sirbu, P. Contreras, C. Johnson, A. Wree, D. Povero, M. Lazic, A. Feldstein
Journal: Journal of Hepatology (2013)
Abstract 1820: TP63 regulation of epithelial to mesenchymal transition in an experimental prostate cell model.
Authors: Jan Roger Olsen, Anne Margrete Øyan, Kari Rostad, Margrete R. Hellem, Jie Liu, Lisha Li, David Micklem, Hallvard Haugen, James B. Lorens, Xisong Ke, Varda Rotter, Biaoyang Lin, Karl-Henning Kalland
Journal: Cancer Research (2013)

Abstract Background: p63 is a transcription factor that is central for epithelial homeostasis and development. In our cell culture model of epithelial to mesenchymal transition (EMT) in a human prostate cells, p63 was one of the most down-regulated transcription factors during EMT. This led us to investigate the role of p63 in EMT by a gain and loss of function approach. Results: Over-expression of the predominant epithelial isoform ΔNp63α in mesenchymal EPT1 and EPT2 cells led to gain of several epithelial characteristics without resulting in a complete mesenchymal to epithelial transition (MET). When p63 was knocked down in epithelial EP156T cells complementary results were observed. Global gene expression analyses found that ΔNp63α induced gene modules involving cell adhesion genes in mesenchymal like cells. ChIP-seq analyses confirmed the enriched binding of p63 to regulatory areas of genes associated with cell adhesion in prostate epithelial cells. CDH1 and ZEB1 are two elemental factors in the control of EMT. Over-expression and knockdown of these factors, respectively, were not sufficient alone or in combination with ΔNp63α for full reversal of the mesenchymal phenotype in EPT cells. Conclusion: The partial reversion of epithelial to mesenchymal transition might reflect the ability of ΔNp63α, as a key co-ordinator of several epithelial gene expression modules, to reduce epithelial to mesenchymal plasticity (EMP). The potential of reduced EMP in order to counteract metastasis and the utility of ΔNp63α expression in this regard may provide a novel strategy to counteract the metastatic process. Citation Format: Jan Roger Olsen, Anne Margrete Øyan, Kari Rostad, Margrete R. Hellem, Jie Liu, Lisha Li, David Micklem, Hallvard Haugen, James B. Lorens, Xisong Ke, Varda Rotter, Biaoyang Lin, Karl-Henning Kalland. TP63 regulation of epithelial to mesenchymal transition in an experimental prostate cell model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1820. doi:10.1158/1538-7445.AM2013-1820
EGFR and HER2 signals play a salvage role in MEK1-mutated gastric cancer after MEK inhibition
Authors: Takuro Mizukami, Yosuke Togashi, Shunsuke Sogabe, Marco A de Velasco, Kazuko Sakai, Yoshihiro Fujita, Shuta Tomida, Takako Eguchi Nakajima, Narikazu Boku, Kazuto Nishio
Journal: Annals of Oncology (2015)
Abstract 2952: Gene expression profiling in gastric adenomas and carcinomas
Authors: Won Kyu Kim, Kwi Hye Koh, Suk Woo Nam, Hwanseok Rhee, Hoguen Kim, Kim Hyunki
Journal: Cancer Research (2010)

Abstract A subset of gastric carcinogenesis is a multistep process, which progresses from chronic gastritis, atrophy, intestinal metaplasia, adenoma and finally leads to gastric carcinoma. To explore the transcriptomic change during the gastric adenoma-carcinoma sequence, a total 26 snap-frozen samples (8 paired normal mucosa, adenoma and carcinoma cases and additional 2 carcinomas) were analyzed by oligonucleotide microarrays. We identified 60 gradually up and down regulated genes according to normal, adenoma and carcinoma sequence. Twenty one genes were gradually decreased from normal mucosa to adenoma to carcinoma and 39 genes were gradually increased. We validated the expression of hydroxyprostaglandin dehydrogenase 15 (HPDG15), follistatin-like 1 (FSTL1), trefoil factor 1 (TFF1) and trefoil factor 2 (TFF2) by real time RT-PCR. The identified gene sets according to adenoma-carcinoma sequence might play critical roles in gastric carcinogenesis. 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 2952.
Growth-Related Glycogen Levels of Human Intestine Carcinoma Cell Lines Grown In Vitro and In Vivo in Nude Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Monique Rousset, Elisabeth Dussaulx, Guillemette Chevalier, Alain Zweibaum
Journal: JNCI Journal of the National Cancer Institute (1980)

The relationship known to exist in vitro between glycogen accumulation and the growth of malignant human intestine epithelial cells was investigated in vivo. The glycogen concentration of 7 human intestine carcinoma cell lines (Caco-2, HT-29, HRT-18, HCT-8R, CO-115, SW-480, and HuTu 80) was measured during cell growth for the in vitro series and during the course of tumor growth for the in vivo series. The glycogen stores were compared for these cells in vitro and after their injection in noninbred Swiss athymic nude mice. The tumors and cultured cells were ranked identically on the basis of glycogen level (Caco-2 > HRT-18 > HT-29 > HCT-8R > CO-115 > SW-480 > HuTu 80). Values for the tumors ranged from 128.8 +/- 10.8 micrograms glycogen/mg protein for Caco-2 tumors down to 2.9 +/- 0.9 micrograms for HuTu 80 tumors; similar values were found for the exponentially growing corresponding cultured cells. The tumor glycogen concentration was independent of the host's nutritional state: Glycogen concentration differed from one type of tumor to another despite its constant level in the liver; fasting did not cause tumor glycogenolysis. By the two experimental approaches, results varied during the growth phases: Stationary phase glycogen concentration increased threefold to fourfold for all cultured cell lines; tumor glycogen concentration, by contrast, was stable throughout the growth period. An inverse relationship was nonetheless found between the rate of tumor growth and tumor glycogen concentration; the highest glycogen content was associated with the slowest growing tumors, and conversely. Apparently, elevated glycogen concentration is regularly associated with decreased cell division rates in vitro and in vivo.
Abstract 1115: Epigenetic regulation of BRCA-1 by xenobiotic and dietary ligands of the aryl hydrocarbon receptor
Authors: Donato F. Romagnolo, Ornella I. Selmin, Andreas J. Papoutsis
Journal: Cancer Research (2010)

Abstract Mutations of BRCA-1 account for only 5-10% of breast cancer cases, whereas sporadic breast tumors represent the remaining 90-95%. In sporadic breast cancers there is silencing of BRCA-1 in the absence of mutations. Factors contributing to this etiology may include environmental ligands of the aryl hydrocarbon receptor (AhR) such as dioxins (ex.2,3,7,8 tetrachlorodibenzene(p)dioxin, TCDD) and polycyclic aryl hydrocarbons (PAHs). Dietary ligands of the AhR with potential protective effects include the phytoalexin resveratrol found in grapes. In this study, we investigated the mechanisms responsible for repression of BRCA-1 expression by the activated AhR. The results of DNA binding studies in MCF-7 breast cancer cells documented that TCDD-induced the association of the AhR to xenobiotic responsive elements (XRE) harbored in the BRCA-1 promoter region. The cotreatment with resveratrol reduced AhR recruitment in a dose-dependent fashion, prevented the TCDD-dependent repression of BRCA-1 transcription and restored BRCA-1 protein expression. The treatment with TCDD induced the recruitment of histone deacetylase-1, DNA methyltransferase-1, methyl-binding protein-2, and reduced the association of acetylated histone-4 and acetylated histone-K9. These effects were abrogated by cotreatment with resveratrol. We propose that dietary antagonists of the AhR such as resveratrol may be useful in the prevention of epigenetic BRCA-1 silencing. 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 1115.