tbuckley/cabot-search huggingface dataset:
Capturing Changes in the Brain Microenvironment during Initial Tumor Cell Invasion.
Authors: M. Lorger, B. Felding-Habermann
Journal: Cancer Research (2009)

Abstract Brain metastases occur mostly in patients with melanoma or primary tumors in the lung, breast or prostate. As therapies against primary tumors and extracranial metastases are improving and patients live longer, the incidence of brain metastases is increasing and brain lesions are seen in 20 to 40 % of patients with advanced metastatic disease. Unfortunately, no therapies are available to treat brain metastasis efficiently.Existing in vivo models of brain metastasis focus mainly on established macrometastases, while very little is known about the initial events of tumor cell brain colonization. In the present study, we used non-invasive bioluminescence imaging and detailed immunohistochemistry to capture the early events of tumor cell interaction with the cerebral microvasculature and invasion of the brain tissue. We used MDA-MB-435 metastatic cancer cells as a model because of their aggressive metastatic phenotype, and injected the cells into the internal carotid artery of immune deficient mice. Our results show that single cancer cells extravasate into the brain parenchyma 3 to 7 days after they arrest within brain capillaries and disrupt the vessel wall, bursting the microvasculature. Cancer cell arrest and extravasation occur exclusively in small vessels that are surrounded by pericytes and lack smooth-muscle cells. Early brain colonization consistently induces local activation of astrocytes, involving heterogeneous astrocyte populations. Reactive astrocytes express high levels of MMP-9 that may assist tumor cell invasion and provide first pro-angiogenic clues. Activated astrocytes consistently persist in the vicinity of growing metastases, and potentially contribute to metastatic proliferation. Occasionally, early host responses also include microglia with stellate or a reactive amoeboid morphology. Importantly, in addition to yielding actively proliferating macrometastases, tumor cell extravasation also leads to widespread single tumor cells dispersed throughout the brain tissue. The majority of these cells remains viable but stays quiescent and does not proliferate. We speculate that the diversity in early local responses of the brain microenvironment to initial cancer cell invasion contributes to the fate of extravasated tumor cells. An early involvement of diverse host cell types might provide distinct environmental clues and co-determine whether a single cell progresses to macrometastasis or remains dormant. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4162.
“5-a-Day for Better Health” Program is Launched in Boston
Authors: Tom Reynolds
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article “5-a-Day for Better Health” Program is Launched in Boston Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 21, 6 November 1991, Pages 1538–1539, https://doi.org/10.1093/jnci/83.21.1538 Published: 06 November 1991
Coated Oral 5-Aminosalicylic Acid Therapy for Mildly to Moderately Active Ulcerative Colitis
Authors: Kenneth W. Schroeder, William J. Tremaine, Duane M. Ilstrup
Journal: New England Journal of Medicine (1987)

We assessed oral 5-aminosalicylic acid (5-ASA) prepared with a pH-sensitive polymer coating in 87 patients with mildly to moderately active ulcerative colitis in a double-blind, placebo-controlled trial. Patients were randomly assigned to receive 5-ASA at a dosage of either 4.8 or 1.6 g per day or placebo for six weeks. The outcome was monitored by flexible proctosigmoidoscopic examinations and physicians' assessments at three-week intervals and by patients' recordings of daily symptoms. Results showed 24 percent complete and 50 percent partial responses in those receiving 4.8 g of 5-ASA per day as compared with 5 percent complete and 13 percent partial responses in those receiving placebo (P<0.0001, rank-sum test). At a dosage of 1.6 g per day, the response was twice as good as with placebo, but the difference did not reach statistical significance (P = 0.51). Age, sex, duration of disease, duration of active symptoms, or extent of disease did not affect the clinical outcome. We conclude that oral 5-ASA administered in a dosage of 4.8 g per day is effective therapy, at least in the short term, for mildly to moderately active ulcerative colitis. (N Engl J Med 1987; 317:1625–9.)
P88 The Aintree Hospital Pleural Disease Training Programme: achieving competency in intercostal drain insertion and in management of pleural problems on the 'acute take'
Authors: B. Chakrabarti, L. G. Spencer, A. Kwok, P. Albert, C. J. Warburton, J. E. Earis
Journal: Thorax (2010)

A key recommendation from the NPSA Rapid Response Report is that intercostal drains should only be inserted by staff who have received appropriate training. Aintree Hospitals NHS Trust has developed an educational programme to improve the management of pleural problems presenting on the ‘Acute Take’ which complies with this NPSA directive. This study evaluates this programme together with ‘prior knowledge’ from the BTS Education Hub e-learning programme (Pleural Aspiration and Insertion of a Seldinger Chest Drain). <h3>The Aintree Pleural Disease Training Programme</h3> The programme, introduced in 2009, is a 4 h ‘hands on’ course consisting of: Lectures covering the indications, technique and pitfalls of drain insertion coupled with real case histories focusing on common ‘out of hours’ scenarios. ‘Hands on’ experience of ‘Seldinger’ and ‘Blunt dissection’ drain insertion using porcine ribcages fixed to resin torso models giving a ‘lifelike’ feel. Practical management of underwater seals and suction. Candidates had to demonstrate competence in drain insertion to a Faculty member before receiving certificates of course completion. <h3>Programme evaluation</h3> COPD, chronic obstructive pulmonary disease, TIA, transient ischemic attack, ACS, acute coronary syndrome (angina, unstable angina, non-ST elevation myocardial infarction and myocardial infarction), ABG, arterial blood gas. 19 candidates were provided with an individual licence to use the BTS module (£75 per licence) and were instructed to undertake the programme and on-line assessment before attending the practical session. Evaluation was with a VAS ranging from 5 (‘very much’) to 1 (‘not at all’). All found the course and e-module high quality, the correct level, easy to use and felt it gave them confidence to safely perform pleural procedures and drain insertion (17 gave rating of 5 or 4). 18 gave 5 or 4 for the course fulfilling its objectives. Despite instructions to complete the e-assessment only 10 (53%) did so. Of these the mean test score was 64% (SD 21 range 11–91%). <h3>Conclusion</h3> A programme combining e-learning, assessments, lectures and ‘hands on’ experience in intercostal drain insertion using animal models represents an effective means of training for the acute take. The BTS e-learning module proved to be a very useful prior knowledge resource but in future, satisfactory performance for the online test will be a pre-requisite to undertaking the clinical skills session.
Gastric emphysema after endoscopic submucosal dissection
Authors: Y. Hyun, D. Han, H. Lee, J. Bae, C. Eun
Journal: Endoscopy (2011)

A 62-year-old male patient with underlying Type 2 diabetes mellitus and hypertension underwent screening esophagogastroduodenoscopy. A 5-cm flat nodular mucosal lesion, which was confirmed to be high grade dysplasia, was noted at the upper body along the lesser curvature, just below the cardia ([Fig. 1]).
Abstract 308: δ-Catenin/NPRAP/Neurojungin mutation promotes prostate tumorigenesis in mice overexpressing Myc oncogene .
Authors: Jongdee Nopparat, Jiao Zhang, Yan-Hua Chen, Qun Lu
Journal: Cancer Research (2013)

Abstract Prostate cancer is the most common non-cutaneous malignant neoplasm in men in Western countries. In humans, prostate cancer progresses from precursor lesions, termed prostatic intraepithelial neoplasia (PIN), to overt carcinoma confined to the prostate, and finally to metastatic disease that often results in lethality. Previous studies in our laboratory have shown that δ-catenin/NPRAP/Neurojungin (gene designation: CTNND2), a primarily neural-enriched protein in the brain of healthy individuals, is overexpressed corresponding to human prostate cancer progression. This finding has led us to investigate the roles of δ-catenin in prostate cancer progression. We utilized a novel transgenic model of mouse prostate cancer with overexpression of human Myc oncogene driven by rat-probasin promoter as the initiating event, which has been proven to mimic human disease conditions. These Myc overexpressing mice were further crossbred with δ-catenin mutant (δ-cat−/−) mice whose exon 9 of δ-catenin gene was disrupted. In this study, we examined the histological differences of mouse prostate in wild type and Myc overexpression with δ-catenin mutant mice (Myc/δ-cat−/−). We observed that morphological alterations characteristic of high grade PIN developed in luminal epithelial cells of transgenic mice by 6 weeks. These changes include an increase of nuclear size, multi-layering, and cribriform formation. Surprisingly, Myc/δ-cat−/- mice at 6 months of age displayed the dramatically increased tumor size and progression from PIN to adenocarcinomas. We also discovered that Myc/δ-cat−/- mice increased in both number of proliferating cells and cells undergoing apoptosis compared with that of wild type animals. However, in Myc/δ-cat−/- mice, proliferative index was greater than apoptotic index by 3.7 fold. Collectively, our findings suggest that mutation of δ-catenin may contribute to tumorigenesis of mouse prostate by enhancing the effects of Myc oncogene resulting in an increase of cell proliferation and thereby promoting prostate tumor growth. Supported by NIHCA111891 and NIHCA165202. Citation Format: Jongdee Nopparat, Jiao Zhang, Yan-Hua Chen, Qun Lu. δ-Catenin/NPRAP/Neurojungin mutation promotes prostate tumorigenesis in mice overexpressing Myc oncogene . [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 308. doi:10.1158/1538-7445.AM2013-308
P670 POST-INFECTIOUS PERIPHERAL NERVOUS SYSTEM DISORDERS AND HEPATITIS E VIRUS
Authors: R.G. Madden, B. van den Berg, J.J.J. van Eijk, A.A. van der Eijk, J.G. Hunter, A.P. Tio-Gillen, J. Reimerink, R.P. Bendall, S.D. Pas, V. Ellis, N. van Alfen, L. Beynon, L. Southwell, B. McLean, B.G.M. van Engelen, B.C. Jacobs, H.R. Dalton
Journal: Journal of Hepatology (2014)
A2.3 Tapering infliximab in ankylosing spondylitis: can we reduce costs?
Authors: P Ávila-Ribeiro, E Vieira-Sousa, H Canhão, J E Fonseca
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Introduction</h3> The approved dose for infliximab (IFX) in the treatment of ankylosing spondylitis (AS) is 5 mg/kg body weight every 6 weeks. Several studies have shown the 3 mg/kg dose to be effective in a subgroup of AS patients but there is few published evidence regarding other dose-reduction regimens, namely adjusting the interval between doses and individualised dose adjustment. We analysed AS patients disease activity upon increasing IFX administrations intervals on an individual basis. <h3>Methods</h3> The Rheumatic Diseases Portuguese Register (Reuma.pt) was used to select all patients diagnosed with AS, under IFX therapy for ≥4 months, followed at Santa Maria Hospital. All patients received IFX 5mg/kg at 0,2 and 6 weeks and thereafter at variable intervals, between 6 and 11 weeks, on an individual basis, determined by clinical judgement. Clinical remission was defined as an ASDAS &lt; 1.3 for ≥4 months and recurrence as an ASDAS ≥ 1.3 during 2 or more consecutive visits. <h3>Results</h3> 50 patients were followed for a mean time of 57 ± 35 months. 72% were males and the mean age at baseline was 45 years. 11 patients (22%) were maintained on IFX every 6 weeks, 12 (24%) increased the interval between doses immediately after week 6 and 23 (54%) increased interval between doses later than week 6. The mean time between starting infliximab and the decision to increase dose intervals was of 18.2 ( ± 11.1) months. 10 patients (26% of those who increased dose intervals) had an ASDAS &lt; 1.3 when the decision to increase dose intervals was taken. 21 patients (42%) further achieved remission, with the physician determined regime, 21.5 ± 28.1 months after starting IFX. Regarding these patients, the majority 16 (76%) showed persistent remission, while 5 (24%) had recurrence of activity, on average 12.9 months after remission. At the last visit 19 (90%) were in remission. <h3>Conclusion</h3> This study confirms that increasing IFX administration intervals can be performed in clinical practice in a subgroup of patient without worsening of disease activity. A high percentage of patients achieved remission (42%) and maintained it through follow-up (32%) based in an individual adjustment regime, determined by the physician decision.
REAL WORLD COMPARISON OF MAJOR BLEEDING RISK AMONG NON-VALVULAR ATRIAL FIBRILLATION PATIENTS NEWLY INITIATED ON APIXABAN, WARFARIN, DABIGATRAN OR RIVAROXABAN: A 1:1 PROPENSITY-SCORE MATCHED ANALYSIS
Authors: Gregory Lip, Allison Keshishian, Shital Kamble, Xianying Pan, Leah Burns, Jack Mardekian, Cristina Masseria, Amanda Bruno, Hemant Phatak
Journal: Journal of the American College of Cardiology (2016)
Invasion and proliferation kinetics in enhancing gliomas predict IDH1 mutation status
Authors: Anne L. Baldock, Kevin Yagle, Donald E. Born, Sunyoung Ahn, Andrew D. Trister, Maxwell Neal, Sandra K. Johnston, Carly A. Bridge, David Basanta, Jacob Scott, Hani Malone, Adam M. Sonabend, Peter Canoll, Maciej M. Mrugala, Jason K. Rockhill, Russell C. Rockne, Kristin R. Swanson
Journal: Neuro-Oncology (2014)

Glioblastomas with a specific mutation in the isocitrate dehydrogenase 1 (IDH1) gene have a better prognosis than gliomas with wild-type IDH1. Here we compare the IDH1 mutational status in 172 contrast-enhancing glioma patients with the invasion profile generated by a patient-specific mathematical model we developed based on MR imaging. We show that IDH1-mutated contrast-enhancing gliomas were relatively more invasive than wild-type IDH1 for all 172 contrast-enhancing gliomas as well as the subset of 158 histologically confirmed glioblastomas. The appearance of this relatively increased, model-predicted invasive profile appears to be determined more by a lower model-predicted net proliferation rate rather than an increased model-predicted dispersal rate of the glioma cells. Receiver operator curve analysis of the model-predicted MRI-based invasion profile revealed an area under the curve of 0.91, indicative of a predictive relationship. The robustness of this relationship was tested by cross-validation analysis of the invasion profile as a predictive metric for IDH1 status. The strong correlation between IDH1 mutation status and the MRI-based invasion profile suggests that use of our tumor growth model may lead to noninvasive clinical detection of IDH1 mutation status and thus lead to better treatment planning, particularly prior to surgical resection, for contrast-enhancing gliomas.
Abstract 67: High-throughput cellular assays for interrogating epigenetic histone modifications
Authors: Tina Hallis, Kun Bi, Thomas Machleidt, Spencer Hermanson, Jennifer Wilkinson, Justin Wetter
Journal: Cancer Research (2011)

Abstract Epigenetic histone modifications such as, methylation, acetylation, and phosphorylation play important roles in regulating the structure and functions of histones which in turn regulate essential gene expression. Dysregulation of the enzymes responsible for these modifications has been linked to cancer and many other diseases. In particular, histone deacetylases (HDACs) and histone methyl transferase (HMTs) have been a recent focus for drug discovery. However, detection of these enzymatic activities in an HTS cell-based format has remained challenging, especially since many of these enzymes may require the formation of protein complexes for relevant activity. To help overcome these challenges, we have developed and validated high-throughput compatible LanthaScreen® cellular assays for the analysis of histone methylation, acetylation, and phoshorylation, in cell backgrounds of interest. The acetylation, methylation and phosphorylation of H3 at specific residues can be detected with terbium-labeled antibodies against the specific site and modification. The expression of GFP-H3 substrate allows for detection of antibody binding in cell lysates via TR-FRET between the terbium and GFP. Since the actual modification takes place in the intact cell, native protein complexes that may be important for enzyme function are preserved. Together, these assays enable interrogation of multiple enzymatic activities responsible for epigenetic modifications of challenging histone targets 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 67. doi:10.1158/1538-7445.AM2011-67
Trial of prophylactic mastectomy is needed
Authors: C Palmieri
Journal: BMJ (1999)

EDITOR—I agree with Fentiman that all cases of prophylactic mastectomy should be centrally registered, but his proposals should go further to maximise the potential information from this group of women.1 The proposals should include compulsory testing of all women undergoing the operation for known mutations of the BRCA1 and BRCA2 genes; a central archive should be established for storing part of the mastectomy specimen, and a chemopreventive trial should be considered.

The first measure is crucial to allow research …
Abstract 2503: Efficient crosspresentation of oncofetal antigen (Glypican-3)-derived long peptides encompassing CTL and promiscuous Th cell epitopes using a novel liposome
Authors: Mohammad A. Sayem, Yusuke Tomita, Akira Yuno, Masatoshi Hirayama, Atsushi Irie, Hirotake Tsukamoto, Satoru Senju, Eiji Yuba, Toshiaki Yoshikawa, Kenji Kono, Tetsuya Nakatsura, Yasuharu Nishimura
Journal: Cancer Research (2015)

Abstract Glypican-3 (GPC3), a human oncofetal antigen, is specifically overexpressed in hepatocellular carcinoma (HCC) and melanoma cells. GPC3-derived short peptides (SPs) vaccine carrying CTL epitopes were safe, and induced measurable immune and some clinical responses in a phase I clinical trial for treatment of HCC (Clin Cancer Res 18:3686, 2012). In this study we aim to identify GPC3-derived long peptides (LPs) carrying promiscuous HLA class II-binding Th1 cell epitopes. We predicted five candidate LPs using computer algorithm and proved antigenicity of all five GPC3-LPs to induce specific CD4+ T-cells by IFN-γ-ELISPOT assays. To determine the restriction HLA molecules involved in antigen presentation, blocking of antigen-induced IFN-γ production was investigated by adding anti-HLA-class II monoclonal antibodies (mAbs). Determination of specific restriction HLA molecules were carried out using L cells transfected with single pair of HLA class II α and β genes or allogeneic PBMC with shared HLA-class II molecule and found that these Th cells were restricted by seven frequent HLA class II molecules. Majority of these Th cell lines secreted Th1-type cytokines in response to autologous PBMCs pulsed with the cognate LPs. Th cells induced by four GPC3-LPs responded to autologous DCs pre-loaded with recombinant human GPC3 suggesting a possible natural processing of these LPs from GPC3 protein. One of the LPs was well cross-presented to GPC3-SP-specific CTLs when they were cocultured with DCs preloaded with GPC3-LPs encapsulated in a novel pH-sensitive liposome that can deliver LPs from endosome to cytoplasm. HLA-A2 transgenic mice immunized with the same LP showed increased GPC3-SP-specific and HLA-A2-restricted CTL response as compared to mice immunized with GPC3-SP alone. A part of this augmented response may be attributed to the help of CD4+ T cell response, because this LP stimulated specific mouse I-Ab-restricted CD4+ T cell response in vivo. GPC3-LPs-specific and HLA-Class II-restricted T cell responses were also observed in 12 out of 20 HCC patients vaccinated with GPC3-SPs. These GPC3-LPs may be applicable to immunotherapy of HCC. Citation Format: Mohammad A. Sayem, Yusuke Tomita, Akira Yuno, Masatoshi Hirayama, Atsushi Irie, Hirotake Tsukamoto, Satoru Senju, Eiji Yuba, Toshiaki Yoshikawa, Kenji Kono, Tetsuya Nakatsura, Yasuharu Nishimura. Efficient crosspresentation of oncofetal antigen (Glypican-3)-derived long peptides encompassing CTL and promiscuous Th cell epitopes using a novel liposome. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2503. doi:10.1158/1538-7445.AM2015-2503
Kaposi sarcoma-associated herpes-like virus (human herpesvirus type 8) DNA sequences in multicentric Castleman's disease: is there any relevant association in non-human immunodeficiency virus-infected patients? [letter; comment]
Authors: A Gessain, A Sudaka, J Briere, N Fouchard, MA Nicola, B Rio, M Arborio, X Troussard, J Audouin, J Diebold
Journal: Blood (1996)
“Circular reddish lesions”: a possibly characteristic endoscopic finding in Henoch-Schönlein purpura
Authors: H. Kishikawa, J. Nishida, S. Takarabe, K. Arahata, A. Ito, J. Miyoshi, S. Kaida, T. Hibi
Journal: Endoscopy (2013)

Henoch–Schönlein purpura is a systemic vasculitis that presents with palpable purpura, abdominal pain, arthritis, and hematuria [1]. The initial clinical symptom of the characteristic purpura makes diagnosis easy. However, the disease is often under-recognized in the 10 % – 15 % of patients in whom gastrointestinal symptoms precede the cutaneous lesions [2]. We report some possibly characteristic endoscopic findings in two cases of Henoch–Schönlein purpura that would be useful in diagnosing precisely this clinical manifestation of the condition.
SAT0385 Monosodium Urate Crystal-Induced Interleukin-1Beta Expression is Related to P62 Level in Autophagy Process
Authors: S.-K. Kim, J.-Y. Choe, H. J. Kim
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> It has demonstrated that functional impairment of autophagy-related (Atg) genes including Atg16L1 and Atg5 enhanced interleukin-1b (IL-1b) expression response to monosodium urate (MSU) crystals. This study investigated whether process of autophagosome formation involved in IL-1b production in MSU crystal-induced inflammation <h3>Methods</h3> IL-1b, tumor necrosis factor-a (TNF-a), and IL-6 mRNA expressions were measured by quantitative real time-polymerase chain reaction (qRT-PCR). Expression for p62, Cullin-3, microtubule-associated protein 1 light-chain 3 (LC3)-I/II, ubiquitin, and mitogen-activated protein kinase (MAPK)-related proteins was measured by immunoblotting. This study used siRNAs for Atg16L1, IL-1b, and p62 for silencing each target gene. <h3>Results</h3> MSU crystals lead to accumulation of p62, which is related with suppression of proteasomal degradation, whereas MSU crystals itself induce LC3-II rather than LC3-I, implicating enhanced autophagosome formation. Enhanced p62 by MSU crystals results in IL-1b expression through ERK signal out of MAPK pathway. Impaired autophagosome formation by siRNA Atg16L1 enhanced more p62 levels and then amplified IL-1b expression. IL-1b also induces p62 protein, and IL-1b blockade reduced p62 levels. <h3>Conclusions</h3> This study demonstrated that MSU crystal-induced IL-1b expression might be related to p62 level through the regulation of proteasomal and autophagolysosomal degradation in autophagy process. It suggests that p62 could be a potent therapeutic target for gout inflammation. <h3>Disclosure of Interest</h3> None Declared