tbuckley/cabot-search huggingface dataset:
Abstract 2035: The effect of KLF5 on cell cycle progression depends upon p53 status
Authors: Yizeng Yang, Dongming Lai, Marie-Pier Tetreault, Jonathan P Katz
Journal: Cancer Research (2012)

Abstract Background: p53 mutation is one of the most common genetic events in esophageal squamous cell cancer (ESCC), and loss of Krüppel-like factor 5 (KLF5) in the context of p53 mutation transforms primary esophageal squamous epithelial cells. Interestingly, while KLF5 promotes proliferation in non-transformed esophageal squamous epithelial cells, KLF5 is growth inhibitory in ESCC. The mechanisms of this context dependent effect of KLF5 on cell Hypothesis: We hypothesized that the effect of KLF5 on cell cycle progression is dependent on p53 status. Methods: Human primary esophageal keratinocytes with or without either wild type or mutant p53R175H were transduced with lentivirus expressing inducible KLF5 shRNA or control. We investigated cell proliferation by MTT assay and cell cycle progression by flow cytometry. The expression of the cyclins and cyclin-dependent kinases were assessed by quantitave PCR. p21waf/cip1 activity was determined using a luciferase reporter. Results: In the context of wild-type p53, KLF5 suppression decreased cell proliferation and produced growth arrest at G2/M, with decreases in cyclin A2 and cyclin E1expression. In contrast, KLF5 loss in human primary keratinocytes harboring the common human p53 mutation p53R175H accelerated the cell cycle with more cells in G1/S and increased cyclin D1 expression. Interestingly, KLF5 directly bound within the p53 response elements in the regulatory region of p21waf/cip1 and activated its promoter activity only in cell with mutant p53. In addition, KLF5 suppression diminished p21waf/cip1 responsiveness to UV irradiation and growth factor depletion only in p53 mutant cells. Conclusions: Here, we identify a novel mechanism for context dependent effects of KLF5 on cell cycle via p53. These findings, in combination with the previously-established effects of KLF5 and p53 loss on cellular transformation, suggest that KLF5 is an important brake on the cell cycle and may function as a tumor suppressor in esophageal squamous cell 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 2035. doi:1538-7445.AM2012-2035
Improvement in Cold-Induced Raynaudʼs Syndrome with Administration of Ticlopidine Hydrochloride Detected by Tc-99m DTPA Human Serum Albumin Scintigraphy
Authors: KAMINAGA TATSURO, TAKADA KOUICHI, KUTOMI KIMIKO, IMAI ERIKA, FURUI SHIGERU
Journal: Clinical Nuclear Medicine (2002)

TATSURO, KAMINAGA M.D.; KOUICHI, TAKADA M.D.; KIMIKO, KUTOMI M.D.; ERIKA, IMAI M.D.; SHIGERU, FURUI M.D. Author Information
OC-003 Multicentre Randomised Controlled Study Comparing Carvedilol with Endoscopic Band Ligation in the Prevention of Variceal Rebleeding
Authors: L A Smith, S Dickson, P C Hayes, D Tripathi, J W Ferguson, E H Forrest, D R Gaya, P R Mills, H Suzuki, D Young, A J Stanley
Journal: Gut (2013)

<h3>Introduction</h3> Rebleeding after an initial oesophageal variceal haemorrhage remains a significant problem despite therapy with band ligation ± non-selective ß-blockers. Carvedilol is a vasodilating non-selective ß-blocker with alpha-1 receptor and calcium channel antagonism. It has a greater portal hypotensive effect than propranolol and has been shown to be effective in the prevention of a first variceal bleed. Our aim was to compare oral carvedilol with band ligation in the prevention of rebleeding following a first variceal bleed. <h3>Methods</h3> Patients who were stable 5 days after presentation with a first variceal haemorrhage and had not been taking (or had contraindications to) ß-blockers, were randomised to oral carvedilol (6.25 mg daily then 12.5 mg daily after one week if tolerated) or a band ligation programme. Patients were followed up at clinic after one week, monthly, then 3-monthly. The primary end-point was variceal rebleeding, on intention-to-treat analysis. <h3>Results</h3> 63 patients were randomised, 32 to carvedilol and 31 to banding. Fifty-six (89%) patients had alcohol related liver disease. There was no difference in baseline mean age (51 yrs ± 10.9 and 50 yrs ± 13.0) or median Childs Pugh score (9, IQR 6–11 and 9, IQR 8–11) for patients randomised to carvedilol or banding respectively. Mean follow-up was 29 months. Compliance was 72% and 90% for carvedilol and banding respectively (p = 0.14) and there was no difference in the number of serious adverse events between the two groups. Variceal rebleeding occurred during follow-up in 12 (37.5%) and 9 (29.0%) patients in the carvedilol and banding groups respectively (p = 0.72), with mortality 25.0% and 51.6% respectively (p = 0.058). The differences in outcome the between groups were similar using per protocol analysis. This interim analysis indicates that to show a significant difference in rebleeding, 482 patients would be required in each group. <h3>Conclusion</h3> Carvedilol is not clearly superior to band ligation in the prevention of variceal rebleeding. However there appears to be a survival benefit for patients taking this drug compared with those undergoing banding, which requires further exploration. <h3>Disclosure of Interest</h3> None Declared
Abstract P5-05-06: Spatio-temporal computational modeling of the p53-Mdm2 pathway
Authors: M Sturrock, AM Thompson, MAJ Chaplain
Journal: Cancer Research (2012)

Abstract Background: The p53 transcription factor is a well-established regulator of the cell cycle and key to preventing cancer. In response to a variety of cellular stresses (e.g., DNA damage or oncogene activation) p53 is activated and translocates to the nucleus where it activates transcription of target genes which can induce cell cycle arrest, senescence or apoptosis. One of the target genes for p53 is the gene for Mdm2, a negative regulator of p53 function in cells. Mdm2 represses p53 function through two main mechanisms: by promoting p53 ubiquitination and proteasomal degradation and, through direct inhibition of p53 transcriptional activity. Experimental data have revealed that in response to gamma irradiation, p53 and Mdm2 concentrations exhibit spatial and temporal oscillatory dynamics in individual MCF7 breast cancer cells. The precise function of these oscillations is still under investigation. Method: Using in vitro laboratory data, we have developed a computational model to study the spatio-temporal evolution of the p53-Mdm2 pathway. The model comprises a system of coupled nonlinear partial differential equations, including transport terms and reaction kinetics. The transport is assumed to include both random (diffusion) and active mechanisms with proteins convected in the cytoplasm toward the nucleus, modeling transport along microtubules. Internal structures such as ribosomes and the nuclear membrane are also explicitly modeled. Results: Using computational simulations we have found ranges of values for the model parameters such that sustained oscillatory dynamics occur, consistent with available experimental measurements. To bridge the gap between in vitro and in silico experiments realistic cell geometries using imported images of cells have informed our computational domain. The effects of microtubule-disrupting drugs, proteasome inhibitor drugs, and mutations in the DNA binding site of p53, have been modeled yielding data in agreement with published experimental laboratory studies. Conclusions: This mathematical computational model enables us to compare the effects of clinically relevant therapeutic approaches at the single cell level. In particular, the precise temporal and spatial distributions of p53 can be determined and the cellular consequences modeled. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-05-06.
Recueil des données et de la morbidité-mortalité (RMM) dans un centre privé, à propos d'une série de 2107 cathétérismes rétrogrades thérapeutiques des voies biliaires (CPRE) sur une période de neuf ans (2002–2010)
Authors: M Garret, G Declety, D Fallik, O Fourdan, C Gavillon
Journal: Endoscopy (2012)

Dans quelle mesure la RMM peut nous conduire à modifier notre pratique en endoscopie interventionnelle?
Abstract LB-436: Rectal aberrant crypt foci for estimate of colorectal tumor recurrence: 3-year follow up study
Authors: Takashi Uchiyama, Hirokazu Takahashi, Eiji Sakai, Kunihiro Hosono, Hiroki Endo, Atsushi Nakajima
Journal: Cancer Research (2011)

Abstract Background and Aims: Endoscopic screening and removal of colorectal tumor can reduce colorectal cancer, although surveillance colonoscopy is currently recommended after the initial screening and removal of colorectal tumor due to the possibility of newly developing tumor. Aberrant crypt foci (ACF) serve as surrogate biomarkers of human colorectal carcinogenesis. In this study we aimed to investigate the relationship between ACF and the recurrence of colorectal tumor after endoscopic polypectomy. Methods: We performed high-magnification chromoscopic colonoscopy to identify lower rectal ACF on 82 subjects who underwent endoscopic polypectomy, and surveillance colonoscopy 3 years after baseline polypectomy at Yokohama City University Hospital. Results: Marked elevation of the ACF number at baseline findings was observed in the tumor recurrence patients in comparison with the non recurrence patients (p &amp;lt; 0.01). ROC analysis showed high specificity of the number of ACF for diagnosis of any tumor recurrence. Conclusion: This is the first study to investigate relation between ACF and the recurrence of colorectal tumor after endoscopic polypectomy. These results suggested that ACF is useful for predictive factors for the recurrence of tumor. 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 LB-436. doi:10.1158/1538-7445.AM2011-LB-436
AB0287 Increased expression of CD95 in B cells of 2nd cycle rituximab non-responders
Authors: H.-P. Brezinschek, F. Rainer, R. Lunzer, W.B. Graninger
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Recently, we have shown that in an Austrian rituximab-registry RA-patients with a low percentage of CD95<sup>+</sup> post-switch B cells will benefit more profoundly from a B cell depleting therapy. <h3>Objectives</h3> The purpose of this study was to test whether the frequency of CD95 positive cells within the different B cell subsets would be useful to identify non reponders to rituximab ahead of time. <h3>Methods</h3> Patients with active rheumatoid arthritis despite therapy with TNF-inhibitors were included in the Austrian B Cell surveillance (ABS)-register. DAS28 was determined before and 24 weeks after each rituximab cycle. In addition, peripheral blood mononuclear cells were isolated before the first infusion of a rituximab therapy. Cells were stained with monoclonal antibodies directed towards CD19, CD24, CD27, CD38, CD45 and IgD. To exclude T cells and monocytes CD3 and CD14 were utilized. Five hundred thousand cells were acquired and analyzed using a seven-channel flow cytometry (BD Canto II cytometer, Software FACSDiva). According to their surface staining B cells were divided in naive (CD19+, IgD+, CD27-); IgD memory (CD19+, IgD+, CD27+), post switch (CD19+, IgD-, CD27+) and double negative (CD19+, IgD-, CD27-) cells. In addition, B cells were further characterized using CD95 and CD80. <h3>Results</h3> Twenty six patients have undergone the week 24-analysis after a second cycle of rituximab. Ten patients had a good (38%), 6 a moderate (23%) and 10 (38%) had no EULAR-response. In the non-responder group the frequency of CD95<sup>+</sup> naïve and pre-switch memory B cells was significantly higher compared to responders and healthy controls. Thus, the mean ± SE percent of naïve B cells before the second cycle in nonresponders was 52.8±11.6, 19.1±5.6 in responders (p≤0.0048) and 5.4±0.9 in controls (p≤0.0001), respectively. Within the pre-switch B cell population non-responders had 88.7% ± 14.3 CD95 positive B cells, compared to 72.2% ± 5.3 in responders (p≤0.04) and 38.8% ± 3.0 in controls (p≤0.0001). No significant difference were found between responders and nonresponders in the other B cell subpopulations. <h3>Conclusions</h3> Our preliminary results suggest that the analysis of B cell subsets may help to discriminate 2nd cycle rituximab-responders from non-responders. The percentage of CD95<sup>+</sup> naive B cells may be a candidate marker for the prediction of a therapeutic response to rituximab in RA. <h3>Disclosure of Interest</h3> None Declared
Lesson of the week: Restrictive-constrictive heart failure masquerading as liver disease
Authors: M. D Lowe, A. A Harcombe, A. A Grace, M. C Petch
Journal: BMJ (1999)

Restrictive cardiomyopathy or pericardial constriction should be considered as a cause of hepatomegaly before liver biopsy is undertaken

The clinical features of restrictive or constrictive heart disease can be non-specific, 1 2 and this may delay diagnosis. We describe three patients with heart disease whose initial presentation led to a wrong diagnosis of primary hepatic disease. Potentially hazardous investigations, including liver biopsies, were performed or planned in each case. The true diagnosis was usually prompted by further clinical examination, and all three patients responded well to appropriate treatment. The importance of making the correct diagnosis is emphasised by the potential for surgical cure in these patients.

### Case 1

An 18year old man presented with a five month history of fatigue, anorexia, abdominal distension, and dyspnoea on exertion. Physical examination showed that he was icteric, with an enlarged liver and ascites. Findings at cardiovascular examination were reported as normal, although his jugular venous pressure was not seen. Liver ultrasound and computed tomography showed diffuse hepatic enlargement, and dilated venous sinuses and septal fibrosis were seen in a liver biopsy specimen. The diagnosis remained unclear, but a raised jugular venous pressure and gallop rhythm were detected at further clinical examination. An electrocardiogram showed widened QRS complexes (>140 msec) and diffuse, non-specific repolarisation changes, and chest radiography showed cardiomegaly and pulmonary oedema. There was no evidence of pericardial thickening in thoracic computed tomograms, and at cardiac catheterisation the haemodynamic profile of a restrictive cardiomyopathy was found. The patient was treated with diuretic drugs and subsequent cardiac transplantation was successful.

### Case 2

A 49year old man had an …
EDOXABAN VERSUS WARFARIN IN 841 PATIENTS WITH ATRIAL FIBRILLATION AND PERIPHERAL ARTERIAL DISEASE: INSIGHTS FROM THE ENGAGE AF-TIMI 48 TRIAL
Authors: Jonathan Cunningham, Robert Giugliano, Eugene Braunwald, Marco Trevisan, Francesco Nordio, Ton Oude Ophuis, Mijo Bergovec, Michele Mercuri, Christian Ruff, Marc Bonaca
Journal: Journal of the American College of Cardiology (2016)
Use of a plastic endoprosthesis to successfully treat esophageal perforation following radiofrequency ablation of Barrett’s esophagus
Authors: B. Vahabzadeh, A. Rastogi, A. Bansal, P. Sharma
Journal: Endoscopy (2011)

Barrett’s esophagus is a condition defined by the transformation of normal esophageal squamous epithelium to columnar epithelium containing goblet cells, known as intestinal metaplasia [1]. Barrett’s esophagus is a known precursor to esophageal adenocarcinoma, a condition with increasing incidence [2] [3]. Abnormal histologic changes in nondysplastic intestinal metaplasia may develop progressively, resulting in low grade dysplasia (LGD) or high grade dysplasia (HGD), prior to transforming into adenocarcinoma [4] [5]. The progression to cancer is higher with HGD as opposed to nondysplastic Barrett’s esophagus or LGD [6]. As a result, this population has been targeted for endoscopic therapy in attempts to minimize the risk of cancer. Traditionally, treatment of these patients has been esophagectomy with reported risk of mortality estimated between 3 % and 4 %, even in experienced centers [7]. As such, less invasive endoscopic eradication therapies (EETs) have become increasingly popular, particularly for patients who are not good surgical candidates due to significant co-morbities, and more frequently as an alternative treatment for those who want to avoid esophagectomy. One such modality is endoscopic radiofrequency ablation (RFA), which has been shown to be effective in eradicating dysplastic changes in Barrett’s esophagus [8]. Unfortunately, serious adverse outcomes of endoscopic therapy include bleeding, esophageal stricture and, less frequently, perforation [9]. However, if identified early, these events can be managed successfully during endoscopy. We present a case of esophageal perforation following EET.
The electronic future: What might an online scientific paper look like in five years' time? (Length and other strengths)
Authors: L. Bero
Journal: BMJ (1997)

The main advantages of online publication are less concern about page limits, the possibility of hypertext links to other sources of information, the ability for interaction, and imagery.

So, in five years' time, scientific papers may be very long. With a click of the mouse button, the real data behind the tables could appear and readers will be able to critically appraise a paper on the basis of more complete information. Overall, reporting should improve because all methodological details of the published research will be available. An unanticipated side effect of better reporting may be that fewer papers are accepted by journals, as peer referees will know …
Oral Ganciclovir as Maintenance Treatment for Cytomegalovirus Retinitis in Patients with AIDS
Authors: W. Lawrence Drew, David Ives, Jacob P. Lalezari, Clyde Crumpacker, Stephen E. Follansbee, Stephen A. Spector, Constance A. Benson, Dorothy N. Friedberg, Larry Hubbard, Mary Jean Stempien, Anna Shadman, William Buhles
Journal: New England Journal of Medicine (1995)

Cytomegalovirus retinitis, a sight-threatening infection associated with the acquired immunodeficiency syndrome (AIDS), currently requires lifelong intravenous treatment. An effective oral treatment would be an important advance.
Abstract 1688: Effect of Gefitinib on the reactions of mammalian type I and type II DNA topoisomerases
Authors: Zeki Topcu, Isa Unlukurt, Sevil Zencir
Journal: Cancer Research (2010)

Abstract Developing small molecule inhibitors in anti-cancer drug research is an integral part of clinical oncology. Gefitinib (Iressa) is a promising small molecule inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase. It was shown to have the potential to improve the clinical effectiveness of EGFR-targeted therapies and gained a significant impact in treatment of non-small-cell lung cancer (NSCLC). Over the past years, several naturally occurring and synthetic compounds with anti-cancer activities were shown to exert their actions via interfering with normal DNA topoisomerase reactions. DNA topoisomerases are ubiquitous enzymes that regulate DNA topology by making transient breakages at nucleic acid backbone and rejoining of DNA strands. Topoisomerases carry out their reactions by two different mechanisms; Type I topoisomerases make a single-stranded break in a DNA duplex while type II topoisomerases create transient breaks in both strands of a duplex. In this study we aimed to examine the effects of Gefitinib on these enzymes to extend the evaluation of its biological activities by plasmid supercoil relaxation and kinetoplast decatenation assays for type I and type II topoisomerases, respectively. Our results are discussed in relation to the outcomes of Gefitinib reported in clinical trials, which together would contribute in identifying the mechanisms of Gefitinib-induced tumor cell-killing. Key Words; Gefitinib; DNA topoisomerases; anti-cancer drugs 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 1688.
Hormone therapy use before diagnosis and breast cancer survival in the California teachers study.
Authors: SF Marshall, E Chang, CA Clarke, R Cress, D Deapen, PL Horn-Ross, J Largent, S Neuhausen, P Reynolds, C Templeman, L Bernstein
Journal: Cancer Research (2009)

Abstract Abstract #65 Background: Breast cancer survival appears to be improved by pre-diagnostic use of hormone therapy (HT), but it is unclear from existing studies whether this is attributable to a direct beneficial effect of HT or because HT use encourages the development of certain tumor types with better prognosis. It is therefore important to examine whether the association between HT use and survival still remains after adequate adjustment for tumor characteristics.&amp;#x2028; Methods: The California Teachers Study is an ongoing prospective study of female public school teachers and administrators. These analyses included 2,783 postmenopausal women whose use of HT was known and who were diagnosed with an incident primary invasive breast cancer after joining the cohort in 1995-96 and followed until death or the end of 2005. Incident cancers and tumor characteristics were ascertained through annual linkage with the statewide California Cancer Registry. Deaths were ascertained through annual linkage with the California state mortality files, the Social Security Administration Death Master File and the National Death Index. HT and other covariates were self-reported on the baseline questionnaire. We estimated the relative risk (RR) of breast cancer death stratifying by age in years, and using age in days from breast cancer diagnosis as the time scale (censoring deaths from other causes).&amp;#x2028; Results: During the follow-up period, 159 (5.7%) women died of breast cancer. In unadjusted analysis, former and current HT use, specifically current estrogen-progestin (EP) use (RR=0.37; 0.24-0.57) but also current unopposed estrogen (E) use (RR=0.64; 0.43-0.95), was significantly associated with reduced breast cancer mortality, compared with no HT use. In multivariable analysis, taking into account race, body mass index, smoking history, lifetime physical activity, and co-morbidities, the risk estimates were somewhat attenuated (EP RR=0.40; 0.26-0.63 and E RR=0.67; 0.44-1.00). After additional adjustment for tumor characteristics (stage at diagnosis, estrogen receptor status, number of positive lymph nodes, grade and tumor size) and treatment received (surgery type and radiation) the risk estimates were considerably attenuated (EP RR=0.53; 0.33-0.84 and E RR=0.82; 0.53-1.27).&amp;#x2028; Conclusion: Use of EP before diagnosis was associated with a reduced risk of death due to breast cancer. Use of E was also associated with reduced breast cancer mortality, although the association was not statistically significant after adjustment for indicators of general health, characteristics of the tumor and treatment. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 65.