tbuckley/cabot-search huggingface dataset:
Abstract P2-09-09: Loss of BTG2 Expression in Breast Cancer Predicts Tamoxifen Resistance
Authors: M Takahashi, T Hayashida, M Sakata, H Jinno, Y. Kitagawa
Journal: Cancer Research (2010)

Abstract Background: The B-cell translocation gene-2 (BTG2) belongs to a class of proteins known as the Tob and BTG anti-proliferative protein family. It was shown that estrogen and progesterone suppress BTG2 mRNA for the development of mammary gland. (Kawakubo et al., Oncogene 2004) Expression analysis of BTG2 protein in estrogen receptor (ER) positive human breast cancer was revealed the loss of nuclear expression in 46% of tumors and showed a significant inverse correlation with cyclinD1 expression. (Kawakubo, Hayashida et al., Cancer Res 2006) According to the Oncomine database online, loss of BTG2 expression significantly correlated with increased recurrence rate after tamoxifen monotherapy. Based on these results, we hypothesized that BTG2 expression might be a novel biomarker for predicting the clinical outcome in tamoxifen treatment and analyzed if BTG2 expression affects the sensitivity against tamoxifen both in vitro and in vivo. Method and Results: The cohort of 60 patients treated with adjuvant tamoxifen monotherapy was available online. (Ma et al., Cancer Cell 2004) Comparison of disease-free survival (DFS) of patients whose laser-captured tumors showed positive BTG2 expression versus patients with loss of BTG2 expression revealed an univariate association in the dataset. (log-rank probability, p=0.029) Multivariate analysis indicated that BTG2 resulted independent prognostic factor for DFS (HR, 0.69; 95% CI, 0.495 to 0.963; p=0.029). In vitro cellular proliferation assay to evaluate the cytotoxicity induced by tamoxifen against ER positive cell lines revealed that endogenous BTG2 positive cell line, MCF7 and T47D, showed drug sensitivity, whereas MDA-MB468 expressing loss of BTG2 showed tamoxifen resistance. (MCF7; IC50=7.35uM, T47D; =3.79uM, MDA-MB468; &amp;gt;25.0uM) Tetracycline-inducible BTG2 expression model in MCF7 was developed to assess the cytotoxicity by tamoxifen treatment under the condition of BTG2 overexpression in vitro and in vivo. The cellular proliferation was strongly inhibited by the concomitant administration of tetracyclin and tamoxifen in vitro. The cell line was injected into the mammary fad pad of immunodeficient mice and these were administered water including tetracyclin and/or tamoxifen pellet at the time when the xenografted tumor grew to be over 125mm3 for 3 weeks. The transgene expression was confirmed by both RT-PCR and immunohistochemistry. Tumor growth ratio was significantly suppressed in the concomitant administration of tetracyclin and tamoxifen in comparison with single treatment of tamoxifen or of tetracyclin. Consistently, tumor weight and Ki67 expression were also significantly suppressed in the mice administered both tamoxifen and tetracyclin. Conclusion: Despite further validation studies need to be conducted, BTG2 expression may be useful biomarker to identify patients appropriate for tamoxifen treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-09.
AB0443 A minute inquiry of the complete blood count in patients with clinically active behcet’s disease
Authors: B. Bitik, Y. Ugur, A. Tufan, R. Mercan, M. E. Tezcan, S. Haznedaroglu, B. Goker
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Behçet's disease (BD) is a recurrent multisystemic vasculitis with an unknown etiology. It is postulated that endothelium dysfunction may have a knock-on effect on the coming up pathogenesis. The prominent histopathological feature in BD is perivascular infltration of neutrophils, lymphocytes and monocytes. Platelets also play an active role in the inflammatory process particularly in thrombotic events of BD. Neutrophil/lymphocyte ratio (NLR) is one of the new markers of systemic inflammation which is calculated as the ratio of neutrophil count to lymphocyte count. Mean platelet volume (MPV) reflects the platelet function. The complete blood count(CBC) is a simple, easy to obtain test used in almost all patients in clinical practice. <h3>Objectives</h3> The aim of this study was to investigate the utility of MPV and NLR as a simple predictor for clinical disease activity in BD. <h3>Methods</h3> Retrospective chart review of 104 patients with BD (55 male, 49 female, mean age: 36.4 +/- 8.6 years) and 77 healthy controls (45 male, 32 female, mean age: 36.4 +/- 8.6 years) were done. Clinical data, neutrophil, lymphocyte and platelet counts and MPVs were recorded. <h3>Results</h3> 61 of 104 patients with BD were in the active period. 14 patients had vascular involvement (one of the pulmonary, deep venous trombosis or arterial involvements), 14 had neuro Behcet, 29 had uveitis, 5 had pulmonary involvement, and 50 had mucocutaneous involvement. The serum NLR of active patients were significantly higher than those of inactive BD and controls (P &lt; 0.001). <h3>Conclusions</h3> Our results indicate that NLR are elevated in patients with active BD, suggesting that CBC may serve as a reliable marker for disease activity of BD. <h3>References</h3> Neutrophil to lymphocyte ratio and cardiovascular diseases: a review. Bhat T, Teli S, Rijal J, Bhat H, Raza M, Khoueiry G, Meghani M, Akhtar M, Costantino T. Expert Rev Cardiovasc Ther. 2013 Jan;11(1):55-9. doi: 10.1586/erc.12.159. PMID:23259445[PubMed - in process] New insights into the pathogenesis of Behçet's disease. Pineton de Chambrun M, Wechsler B, Geri G, Cacoub P, Saadoun D. Autoimmun Rev. 2012 Aug;11(10):687-98. doi: 10.1016/j.autrev.2011.11.026. Epub 2011 Dec 11. Review. PMID:22197900[PubMed - indexed for MEDLINE] <h3>Disclosure of Interest</h3> None Declared
Giant Urinary Bladder Stone
Authors: Diego Villasboas-Rosciolesi, Rodrigo Cárdenas-Perilla, Amparo García-Burillo, Joan Castell-Conesa
Journal: Clinical Nuclear Medicine (2014)

A 27-year-old woman presented with a history of recurrent urinary tract infections in infancy and urinary incontinence secondary to lipomyelomeningocele. At the age of 7, she underwent bladder augmentation enterocystoplasty, requiring intermittent catheterization without urinary tract infections until present. A Tc-DTPA renography was performed to evaluate renal function, in which an abnormal tracer distribution was seen in urinary bladder, and furthermore, a retrograde cystography shows a giant bladder stone.
Increased 99mTc TRODAT-1 Uptake in Anaplastic Oligodendroglioma
Authors: Yu-Ren Chen, Te-Chun Hsieh, Kuo-Yang Yen, Chia-Hung Kao
Journal: Clinical Nuclear Medicine (2013)

(99m)Tc TRODAT-1, a selective dopamine transporter SPECT imaging agent, has demonstrated its efficacy in identifying patients with Parkinson disease. Primary or metastatic brain neoplasm uptake of TRODAT-1 is rarely reported in literatures. A 51-year-old female patient underwent TRODAT-1 study for bradykinesia and altered cognitive function; the images showed abnormal extrastriatal uptake in the right frontal lobe subsequent to operation, and pathological examination confirmed anaplastic oligodendroglioma. Care should be taken in interpreting TRODAT-1 image; any focus on abnormal accumulation of radiotracer should not be overlooked because it can be brain neoplasm as demonstrated in this case.
Abstract 2797: Measurement of GST-P1 methylation in body fluids and prostate cancer diagnosis: a meta-analysis
Authors: Tianying Wu, Edward Giovannucci, Jeff Welge, Palash Mallick, Grace LeMasters, Wan-yee Tang, Shuk-Mei Ho
Journal: Cancer Research (2010)

Abstract Prostate-specific antigen (PSA) screening significantly increases the early diagnosis of prostate cancer; however, the specificity of PSA screening is fairly low (20%), leading to many unnecessary biopsies and overtreatment. Hence, the identification of a circulating biomarker with high specificity to complement the traditional PSA test is greatly needed. CpG island promoter hypermethylation may be one of the earliest somatic genome alterations in the development of several types of cancers. Studies have shown that glutathione-s-transferase-π (GST-P1) promoter hypermethylation is the most common somatic genome alteration during prostate cancer development. We have retrieved 22 studies that measured GST-P1 in plasma, urine, buffy coat, ejaculate, or whole blood. In our random effect model, the pooled specificity of measurement of GST-P1 hypermethylation was 89% (95%CI, 71-95%), indicating that GST-P1 has a much stronger specificity than the PSA test. When we stratify the studies by biospecimen type and PCR method, high specificity remains within each stratum. Unlike the PSA test, the pooled sensitivity of the GST-P1 methylation test was 47% (95%CI, 33-61%), relatively low. However, low sensitivity does not downgrade its potential application as a complement to the PSA test, which has a high sensitivity but a poor specificity. Moreover, we have found that the likelihood of GST-P1 methylation tends to increase with prostate cancer pathological stage (stages 3-4 versus 1-2), with an odds ratio of 1.21 (95%CI, 0.99-1.48). However, due to limited sample size (10 studies), this did not reach statistical significance. The current study has several advantages. This is the first study to systemically review GST-P1 methylation as measured in body fluids, and to compare the specificity of GST-P1 to the traditional PSA test; second, this review has rigorously examined specificity by excluding healthy controls, who cannot represent individuals with elevated PSA levels or urological symptoms. 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 2797.
117 SPONTANEOUS DECREASE IN LIVER INJURY DOES NOT STRONGLY PREDICT EVOLUTION OF PATIENTS WITH SEVERE ALCOHOLIC HEPATITIS TREATED WITH CORTICOSTEROIDS
Authors: A. Louvet, F. Artru, M. Colin, G. Lassailly, P. Deltenre, V. Canva-Delcambre, S. Dharancy, P. Mathurin
Journal: Journal of Hepatology (2013)
PTU-016 Entonox vs Sedation in Colonoscopy: a Prospective Cohort Study: Abstract PTU-016 Table
Authors: A Mcculloch, S Muthlagappan, E Harrison, J Mannath, C Nwokolo, R Arasaradnam
Journal: Gut (2013)

<h3>Introduction</h3> Intravenous sedation for colonoscopy is associated with cardiorespiratory risk and delayed recovery. There is also the perception that patients tolerate the procedure better with sedation. Moreover some studies suggest that colonoscopy performance is compromised if patients do not tolerate the procedure well. This study aimed to compare inhaled nitrous oxide (entonox) with intravenous sedation during colonoscopy in terms of completions rates, patient comfort and changes in physiological status. <h3>Methods</h3> 288 patients undergoing elective colonoscopy were included performed by a single endoscopist. Carbon dioxide was used for insufflation. Patients were offered a choice to have intravenous sedation or entonox. Vital signs were recorded before, during and after the procedure. Following the colonoscopy, patients completed a satisfaction survey questionnaire charting symptoms of pain and bloating (modified 10 mm Visual analogue score tool) and the endoscopist scored patient comfort. <h3>Results</h3> Out of the 288 participants, 143 (48 women and 95 men) chose entonox and 145 (66 women and 79 men) opted for sedation. Of those who received entonox intially, 25 were converted to sedation during their procedure (results not reported). For those who had sedation, the mean dose of Midazolam was 2.4 mg (SD 0.6) and Pethidine was 28.5 mg (SD 9.0). The most common indications for colonoscopy in both groups were altered bowel habit, chronic diarrhoea and inflammatory bowel disease surveillance. <h3>Conclusion</h3> Entonox is as effective as intravenous sedation in relieving pain and bloating during colonoscopy without compromising performance. Entonox had less effect on systolic blood pressure suggesting it may be more appropriate in the elderly or those with cardio-pulmonary compromise. <h3>Disclosure of Interest</h3> None Declared
Abstract 1333: Upregulation of chemokines including RANTES/CCL5 upon Toll-like receptor 3 activation in breast cancer: Association with leukocyte infiltration
Authors: Amritha Kalyani Venkatesh, Michelle Pate, Fabian Benencia
Journal: Cancer Research (2010)

Abstract The association of leukocytes with the microenvironment of different tumors and their role in disease progression is well-documented. However, the mechanism of recruitment of leukocytes to the tumor microenvironment remains unclear. In particular, we have previously demonstrated the capability of tumor-associated dendritic cells to promote neovascularization. In this light, toll-like receptors (TLR) have recently been identified as potential players in different cancers such as malignant melanomas, thyroid cancer and pancreatic cancer. These are a family of pattern-recognition receptors that, when activated by a ligand, trigger signaling pathways involved chiefly in the inflammation process of the innate immune system. Here, we investigated the role of TLR-3 in the capability of the tumor cells to generate chemokines capable of attracting leukocytes to the tumor microenvironment. For this purpose we used the 4T1 model of breast cancer in BALB/c mouse. First, we were able to determine the expression of TLR-3 in these cells by PCR analysis. Then, 4T1 mouse breast cancer cells were treated with poly(I:C), a well-known ligand for TLR-3, and the supernatants were checked for the presence of different chemokines (RANTES, SDF-1α, MIP-3α, MIP-3β) by sandwich ELISA. These molecules were selected taking into account that their receptors are present in dendritic cells. Further, a reverse transcription quantitative PCR was performed to detect the RNA expression levels of these chemokines. In both cases, a significant increase in RANTES levels upon TLR-3 activation was observed. Further, a chemokine PCR array showed upregulation of 10 chemokines, RANTES among them, on 4T1 cells stimulated with poly(I:C). A subsequent protein array analysis of different mouse cytokines in poly(I:C)-treated 4T1 cells revealed also an increase in RANTES, IL-6 and MIP-2 and a decrease in the matrix metalloprotease inhibitor TIMP-1. Interestingly, IL-6 upregulation was further confirmed by ELISA. These results are supportive of our hypothesis that TLR-3 activation could lead to the release of chemokines that assist in leukocyte recruitment. Further in vivo studies are required to observe the effect of knocking down TLR-3 in cancer cells on the capability of the tumor to promote leukocyte infiltration. 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 1333.
Legionnaires' Disease—Still with Us
Authors: Sydney M. Finegold
Journal: New England Journal of Medicine (1988)

A dramatic outbreak of pneumonia (182 cases with 29 deaths) in Philadelphia in July 1976 was recognized ultimately as a discrete entity that became known as legionnaires' disease. The announcement by the Centers for Disease Control the following January that the etiologic agent of this disease had been identified as a bacterium came as a big surprise, since conventional bacteriologic techniques and many other studies had failed to yield a cause. Many had believed that essentially all bacterial pathogens had already been discovered and that techniques for their isolation and identification were readily available. Legionella was finally isolated through techniques . . .
ATCT-20BEVACIZUMAB FOR VERY ELDERLY PATIENTS WITH NEWLY DIAGNOSED MALIGNANT GLIOMA
Authors: Satoshi Adachi, Mario Suzuki, Yuzaburo Shimizu, Akihide Kondo, Hajime Arai
Journal: Neuro-Oncology (2015)

Two big clinical studies have shown that the efficacy of bevacizumab for the treatment of newly diagnosed malignant glioma. Some sub-analysis of these studies showed that bevacizumab may keep long the performance status of the patients suffering from these tumors. While Japan is forecasted to become an aging society, with 20% of over 75 year-old people in 2015, it is important for us to maintain the condition of old people good, even if they are living with malignant tumors. Then, we reviewed the safeness and the efficacy of bevacizumab for keeping the performance status over 2 of elder patients who had newly diagnosed malignant glioma. We studied the patients who were older than 75 years and had surgery in our institution with the diagnosis of malignant glioma histopathologically. After the focal radiotherapy, all patients received 15mg/kg bevacizumab every four week with 150mg/kg temozolomide. We experienced one pulmonary embolism but no major complications related to bevacizumab treatments. Furthermore, our data showed the becacizumab was safe for even very elder patients and kept their condition good when compared to the patients without maintenance therapies.
PWE-245 Anti-TNFα antibody therapy and parenteral corticosteroids demonstrate distinct effects in the treatment of experimental<i>Trichuris muris</i>-induced chronic colitis
Authors: S E Levison, M C Little, R K Grencis, J T McLaughlin, J L Pennock
Journal: Gut (2012)

<h3>Introduction</h3> Anti-tumour necrosis factor (TNF) α antibody treatment and corticosteroid therapy represent central strategies in the management of Crohn9s disease. Yet, over 30% of patients fail to respond. Understanding the mechanism of effect for each therapy is complicated by disease heterogeneity, and the complexities of effector and regulatory immune cell responses. We characterised the biological and immunological effects of infliximab and hydrocortisone therapy in a genetically identical murine model of experimental colitis. <h3>Methods</h3> Mice (AKR) susceptible to chronic <i>Trichuris muris</i>-induced colitis were infected with 300 <i>T muris</i> eggs. A single 5 mg/kg dose of Infliximab, or daily hydrocortisone treatment (2 mg/kg, QDS) were administered intraperitoneally once chronic colitis had established (from day 35 post-infection, p.i.). Systemic, mesenteric lymph node (MLN) and colonic effects were analysed at day 45 p.i. MLN cell cytokine bead-array and colonic gene expression (RT-qPCR) analysis were performed. Colonic histopathology, tissue Foxp3<sup>+</sup> and macrophage recruitment were determined. Treated groups were compared to naïve and untreated-infected AKR (n=5 per group). <h3>Results</h3> Neither treatment altered worm expulsion. Anti–TNFα Ab and corticosteroid therapy preserved colonic length, compared to untreated disease. Colonic inflammation was less severe with steroid treatment (p=0.005) and infliximab (p=0.07). An increase in MLN TH2 cytokines was suggested with both treatments. Reduced colonic TNFα, IL-1β, IFNγ and IL-12p40, and increased IL-13 expression were observed following Infliximab. Down-regulated TH1 cytokines, elevated TH2 cytokines (IL-4, IL-5, IL-13), and up-regulated colonic IL-10 expression were detected following corticosteroid treatment. Colonic Foxp3<sup>+</sup> cell numbers increased with disease but were unaltered by either treatment. A significant reduction in tissue F4/80<sup>+</sup> macrophages was observed with infliximab treatment alone. <h3>Conclusion</h3> Anti–TNFα Ab and corticosteroid therapy suppress TH1-driven experimental colitis. Up-regulated transcription of TH2 and regulatory (IL-10, TGFb, Foxp3) pathway molecules was seen with corticosteroid treatment. This was not accompanied by an increased influx of Foxp3<sup>+</sup> T-cell, suggestive that corticosteroids may alter regulatory-cell function more significantly than recruitment, in the reduction of pathology and disease activity. Anti–TNFα Ab treatment reduced colonic pro-inflammatory macrophage recruitment. With differing modalities of immunosuppression demonstrated, this model may increase understanding of why either mode of therapy can induce benefit in man even if the other has failed. <h3>Competing interests</h3> None declared.
PTU-027 Lifetime alcohol consumption in heavy drinkers with and without liver disease. 1: Threshold effect and male-female differences
Authors: D Gleeson, A Ali, J Jones, M Bradley, R Peck, K McCormack
Journal: Gut (2012)

<h3>Introduction</h3> It is unclear whether the risk of alcoholic liver disease (ALD) is related to amount of alcohol consumed (dose effect) or is independent of alcohol consumption above a given threshold (<i>J Hepatol</i> 2004;<b>41</b>:25). The perception that women are more susceptible to ALD than men is based partly on observations that alcohol consumption in women with ALD is less than that of men with ALD. We have previously (<i>Am J Gastro</i> 2008;<b>103</b>:3039) characterised two large cohorts of heavy drinkers (&gt;60 Units/wk (M) or &gt;40 Units/wk (F) for &gt;5 years): patients with decompensated ALD and controls without serious liver disease on clinical, laboratory and ultrasound examination. Here, we aimed to compare total lifetime alcohol consumption (TLA) between these cohorts and to examine male-female differences in consumption. <h3>Methods</h3> Subjects (328 patients, 233 male, mean age 48 yr and 237 heavy-drinking controls, 187 male, mean age 48 yr) completed a lifetime alcohol questionnaire. Total alcohol consumption was calculated and the predominant beverage group recorded, separately, at home and outside home, and during Monday–Thursday and Friday–Sunday. Data were summed over each stable drinking period in the subject9s lifetime. For individual beverage analysis, we assumed that all alcohol consumed in a given circumstance was the stated predominant beverage. Body weight data were available in 216 controls and (pre-fluid overload) in 198 patients. <h3>Results</h3> TLA was (median (IQR)) 118 (80–175) × 10<sup>3</sup> Units in patients and 131 (93–183) × 10<sup>3</sup> units in controls (p=0.041) by Mann–Whitney): 9 (6–12)-fold and 9 (7–12)-fold higher respectively than the minimum specified by the above inclusion criteria. TLA, corrected for body wt was similar in patients and controls. Females with ALD consumed less total alcohol (absolute 85 (52–11) vs 136 (94–193) × 10<sup>3</sup> units (p&lt;0.01) and corrected for wt (p=0.04)), and also, less beer (p=0.001) but more wine (p&lt;0.001) and a trend towards more spirits (p=0.166) over their lifetime than did males with ALD. However, female controls showed similar significant differences from male controls: lower TLA (both absolute 82 (69–119) vs 145 (108–193) × 10<sup>3</sup> Units) and corrected for body weight) and also, less beer, more wine and more spirits (all comparisons p≤0.001). <h3>Conclusion</h3> The higher total alcohol consumption in controls than in patients is more consistent with a threshold effect then a dose effect of alcohol for development of ALD. Male-female differences in consumption are independent of the presence of liver disease and therefore, are not evidence per se of increased female susceptibility to ALD, although the data do not exclude this. <h3>Competing interests</h3> None declared.