tbuckley/cabot-search huggingface dataset:
Constitutive IFN signaling to modulate the immunogenicity of glioma cells.
Authors: Patrick Roth, Sara Nagy, Caroline Happold, Hannah Schneider, Michael Weller, Manuela Silginer
Journal: Journal of Clinical Oncology (2017)

e13528 Background: Interferons (IFN) are cytokines that might be constitutively expressed also in the absence of acute infection and thereby regulate various physiological processes such as cellular proliferation and differentiation, cell viability or immune cell function. Alterations in IFN signaling have been observed in numerous malignancies, but their role in glioblastoma, particularly in glioma-initiating cells, has not been investigated in detail. Methods: We characterized constitutive type I IFN signaling and its functional impact in glioma cells using expression analyses, RNA interference-mediated silencing of various genes involved in the IFN signaling pathway and immune cell lysis assays. Results: We found constitutive expression of pSTAT1 and Myxovirus A (MxA), a classical IFN-response marker, in the absence of exogenous IFN-β in vitro and higher MxA expression in gliomas than in normal tissue in vivo, indicating that IFN signaling is constitutively active in these tumors. Silencing of the type I IFN receptor, IFNAR1/2, or its ligands, IFN-α or IFN-β, decreased MxA levels, providing evidence for the existence of an autocrine type I IFN signaling loop. On a functional level, we observed reduced PD-L1, MHC class I and class II expression and increased susceptibility to immune cell-mediated lysis upon disruption of IFN signaling, suggesting that constitutive IFN signaling in gliomas contributes to the immune evasion of glioma cells. Conclusions: Our findings point to an important role of constitutive IFN signaling in glioma cells in the regulation of anti-tumor immune responses.
BMA annual meeting: GMC must recognise that a lack of resources puts doctors at risk of mistakes, says the BMA
Authors: Abi Rimmer
Journal: BMJ (2017)

The General Medical Council should acknowledge that competent doctors could cause patient harm when working in a “resource starved” environment, the BMA has said.

Delegates at the BMA’s annual representative meeting in Bournemouth on 26 June voted in favour of a motion which said that “in an increasingly stretched and resource starved health service, doctors are being asked to work beyond their capacity.”

The motion called on the BMA to lobby the GMC to amend its …
Real-world effectiveness of fulvestrant monotherapy as first hormonal therapy in metastatic breast cancer patients.
Authors: Temitope O Olufade, Karen E Skinner, Nicola Di Santo, Rahul A. Shenolikar, Mark Stephen Walker, Lee Steven Schwartzberg
Journal: Journal of Clinical Oncology (2017)

e12537 Background: Fulvestrant is a selective estrogen receptor degrader approved as monotherapy for postmenopausal women with estrogen-receptor-positive metastatic breast cancer (MBC) who progress following anti-estrogen therapy. The recent Phase 3 FALCON study for hormone therapy (HT) naïve women showed increased median progression-free survival (PFS) (16.6 months) in fulvestrant treated patients (pts) compared with anastrozole (13.8 months), but real-world data are lacking. This study examined the real-world effectiveness of fulvestrant monotherapy as first (L1) or second line (L2) treatment after MBC diagnosis. Methods: This was a retrospective medical record review from 10 US community oncology practices. Female pts initiated fulvestrant monotherapy as the first HT after MBC diagnosis, administered as L1 or as L2 treatment following L1 chemotherapy. Fulvestrant was initiated between 1/1/2011 and 12/31/2015. Pts were classified as HT naïve; and HT relapse status: early relapse (≤12 months of adjuvant HT completion), late relapse (&gt;12 months). Time to first chemotherapy (TTC), PFS, and overall survival (OS) were evaluated using Kaplan-Meier analyses. Results: The study included 121 pts: mean (SD) age 65.7 (11.4) years, 81.8% Caucasian, 94.2% postmenopausal/undocumented, and 92.0% HER2-/undocumented. Overall, 15.7% were de novo metastatic and 86.0% initiated fulvestrant in L1. At the start of fulvestrant, 40.5% had visceral metastasis. The study results (Table 1) suggest better outcomes (TTC, PFS, OS) in HT naïve and late relapse pts, than early relapse pts. Conclusions: First line fulvestrant in the real-world setting demonstrates comparable PFS benefit to clinical trial results and appeared successful in delaying chemotherapy initiation in HT naïve and late relapse pts. This finding supports the use of fulvestrant monotherapy as the first hormonal therapy in a metastatic setting. [Table: see text]
Evolution de la ditribution de la métaplasie intestinale au sein des endobrachyoesophages
Authors: E Andlauer, A Volant, J Fayçal, L Doucet, F Cholet, JB Nousbaum, H Gouérou, M Robaszkiewicz
Journal: Endoscopy (2005)

Si la filiation métaplasie intestinale – dysplasie – cancer lors de la transformation maligne de l'endobrachyoesophage (EBO) est bien établie, l'histoire naturelle de la métaplasie intestinale est moins bien connue.
Screening for Lynch syndrome in unselected women with endometrial cancer.
Authors: Sarah E. Ferguson, Melyssa Aronson, Lua R Eiriksson, Golnessa Mojtahedi, Aaron Pollett, Steven Gallinger, Amit M. Oza, Helen Mackay, Marcus Bernardini, Jordan Lerner-Ellis, Blaise Clarke
Journal: Journal of Clinical Oncology (2013)

5508 Background: Endometrial cancer (EC) is often the sentinel cancer in women with Lynch Syndrome (LS) however it is often not recognized in this population. A prospective cohort study comparing family history, immunohistochemistry (IHC) for mismatch repair (MMR) proteins, and tumour morphology to germline mutation status in MMR genes was performed in unselected women with EC to determine which screening strategy was superior in identifying women with LS. Methods: All women with newly diagnosed EC between July 2010 and June 2011 were asked to participate in the prospective screening protocol for LS which included completing an extended family history questionnaire (eFHQ), tumor assessment for LS-associated morphologic features and IHC as well as germline mutation testing. Results: 119 (n = 182, 65%) consented to the study. The median age was 61 (26-91), 96 (81%) stage I, and 42 (35%) had high risk histology. There were 6 (7.4%, n = 81) women that were germline mutation positive (MLH1 N=3; MSH6 n = 2; MSH2 n =1), representing a mutation positive rate of at least 5% in this cohort (6/119). All 3 MLH1 mutation positive women had low grade histology while mutations in MSH2/6 were exclusively found in women with high risk histology. Two of the six mutation positive women were not identified by family history. Mutation positivity was higher in women under age 50 (23%; 5/22) compared to women &gt; age 50 (1%; 1/97)( (p = 0.0008). LS-morphologic features were found in 58 (59%, n = 98) women. The sensitivity, specificity, PPV and NPV of the LS-associated features in predicting LS mutation status was 100%, 42.6%, 7.9% and 100% compared to IHC which was 100%, 76%, 18% and 100% and eFHQ which was 67%, 84%, 27%, 97%. Conclusions: In this unselected population of women with newly diagnosed EC the germline mutation rate for LS was 2-3 times that has previously been reported. Previously described LS-associated morphologic features were not specific to germline mutation status and family history missed one third of women with LS. IHC was the best strategy to identify women with EC who should undergo germline mutation testing.
Nuclear Medicine Aspects of Primary and Secondary Liver Cancer
Authors: Jerry W. Froelich, James H. Thrall, Dennis P. Swanson
Journal: Liver Cancer (1985)

Although primary cancer of the liver is relatively rare (1–2% of all cancers), metastatic tumor in the liver is a common disorder. Fifty to 75% of patients who die from cancer have been found to have liver metastases [1–3]. Primary tumors of breast, gallbladder, gastrointestinal, lung, pancreas, and genitourinary origin commonly metastasize to liver.
PROBLEMS CONNECTED WITH THE USE OF PROTAMINE-ZINC-INSULIN
Authors: Henry T. Ricketts
Journal: Annals of Internal Medicine (1937)

ExcerptThe efficacy of protamine insulin in the treatment of diabetes has been convincingly demonstrated by a number of workers2, 3, 6, 9, 11, 12, 13, 14, 15, 18, 19 during the past year. Its superiority over the old insulin as evidenced by better control of the blood sugar, fewer reactions, reduction in the number of daily injections and often an appreciable saving in total requirement cannot be doubted.All investigatorshave recognized, however, that the slow and prolonged action to which protamine insulin owes its conspicuous advantages is also responsible for certain difficulties peculiar to its use. Its seems appropriate...
Place de l'écho-endoscopie et de la cholangio-pancréatographie rétrograde endoscopique dans la prise en charge précoce des pancréatites aiguës biliaires
Authors: Z Houmani, D Pricope, JC Duchmann
Journal: Endoscopy (2005)

But L'écho-endoscopie (EE) est actuellement l'examen de référence pour le diagnostic de lithiase de la voie biliaire principale (LVBP) dont le traitement de choix est représenté par la sphinctérotomie endoscopique (SE). La conférence de consensus sur la pancréatite aiguë n'a pas clairement défini la place de l'EE et de la cholangio-pancréatographie rétrograde endoscopique (CPRE) dans la prise en charge des pancréatites aiguës biliaires (PAB). Le but de l'étude a été d'évaluer la faisabilité et les résultats d'une stratégie couplant EE et CPRE dans la prise en charge diagnostique et thérapeutique précoce des PAB à partir d'un organigramme prédéfini selon les données actuelles de la littérature.
HMPL-523, a Novel SYK Inhibitor Showed Anti-Tumor Activities In Vitro and In Vivo
Authors: Na Yang, Wei Deng, Qiaoling Sun, Junqing Liang, Linfang Wang, Shiming Fan, Renxiang Tang, Ying Yu, Junen Sun, Feng Zhou, Guangxiu Dai, Weiguo Qing, Weiguo Su, Yongxin Ren
Journal: Blood (2016)
Diagnostic échoendoscopique et résection endoscopique d'une tumeur carcinode du rectum
Authors: B Napoléon, C Lefort, V Hervieu, T Ponchon, JA Chayvialle
Journal: Endoscopy (2006)

Un traitement endoscopique peut être proposé pour les tumeurs carcinodes du rectum dont la taille n'excpde pas 1 à 2cm (selon les auteurs). Deux problèmes existent cependant pour espérer un traitement à visée curative: – il ne doit pas y avoir d'extension à la musculeuse; – l'exérèse doit être complète ce qui est rarement le cas quand la lésion est réséquée à l'anse diathermique.
Does concussion education have an impact in behaviours amongst school-age rugby players?
Authors: Chris Bosshardt, Mike England, Akbar de Medici, Courtney Kipps
Journal: British Journal of Sports Medicine (2017)

Background Concussion is a common injury in school-boy rugby, if managed incorrectly it can have serious consequences such as further injury, prolonged symptoms, and second impact syndrome. Adolescent players show poor knowledge levels and symptoms-reporting behaviour. Objective Investigate the effects of an educational presentation on the knowledge and behaviour of school age rugby players regarding concussion. Design Questionnaire based study. Setting 120 male rugby players, aged 16–18. Participants Three large rugby union playing schools in England. Interventions Independent Variable – Educational presentation aimed at school-age rugby players to improve their education and behaviours related to the condition. Players completed a questionnaire testing for likely behavioural responses from a selection of common concussion scenarios. Additional questions assessed knowledge of concussion symptoms, diagnosis and management. The questionnaires were completed pre-season and repeated 2–3 months after the presentation. Outcome Dependent variable: Questionnaire scores. Results The students had significantly improved their responses giving 53.9% appropriate responses after the presentation (Md=55, n=34) compared to 46.1% before ( Md =33.5, n =34) ( U =400, Z =-2.18, p =0.029) with a moderate effect size ( r ?=?0.37). The knowledge of students increased from 37.85% correct responses before ( Md =28, n =35) and 44.07% on follow up?( Md =28, n =35) but with no significant difference ( U ?=?575.5, Z ?=?-?0.88, p =0.378 with a small effect size ( r ?=?0.15)). Completed surveys showed increased awareness of guidelines from 19.4% to 73.2% (p=0.00 McNemars Test). Conclusions The students had showed improved concussion behaviour in response to concussion scenarios at 2–3 month follow up in contrast to previous studies on educational interventions. There was no increase in players knowledge of concussion. The literature shows increases in short-term knowledge with other forms of concussion education but this effect is often lost at long term follow up. There was increased awareness of guidelines. Future concussion education should be modeled on the educational presentation to improve behavioural outcomes.
Effective control measures limited measles outbreak after extensive nosocomial exposures in January-February 2008 in Gothenburg, Sweden
Authors: P Follin, L Dotevall, M Jertborn, Y Khalid, J Å Liljeqvist, S Muntz, I Qvarfordt, A Söderström, Å Wiman, C Åhrén, P Österberg, K Johansen
Journal: Eurosurveillance (2008)

In January-February 2008, one imported case of measles initiated a series of exposures with around 380 nosocomial secondary contacts. Susceptible individuals were traced early and control measures were initiated that managed to limit the consequences considerably. Only four secondary cases were identified by the end of March. This minor outbreak illustrates the importance and efficiency of early control measures as well as the fact that the risk of measles outbreaks still exists in a country that has high measles, mumps, rubella vaccination coverage among children.
Synergistic Killing of Leukemic Cells by Small Molecule Inhibitors of the Pim Protein Kinases and Inactivators of Additional Signal Transduction Pathways.
Authors: Yingwei Lin, Zanna M Beharry, Elizabeth G Hill, Jin H. Song, Wenxue Wang, Zuping Xia, Zhenhua Zhang, Peter D. Aplan, Jon Aster, Charles D Smith, Andrew Kraft
Journal: Blood (2009)
Correlation of 18F-fluorodeoxyglucose (FDG) accumulation with glucose transporter (GLUT-1) expression in oesophageal adenocarcinoma
Authors: AA Raouf, C Power, V Malik, N Ravi, MM Griffin, JV Reynolds
Journal: Endoscopy (2005)

Aims: In this study we evaluated the relation between changes in 18F-FDG-PET uptake and expression of glucose transporter Glut-1 in primary oesophageal adenocarcinoma.
PD-L1 expression of high grade glial tumors at diagnosis and change of expression status at recurrence.
Authors: Basak Oyan, Seyma Eren, Ozlem Sonmez, Ferda Ozkan, Kaan Yaltırak, Ugur Ture
Journal: Journal of Clinical Oncology (2017)

2035 Background: PD-L1 expression status is the main predictive factor for response to immune checkpoint inhibitors. PD-L1 status may change over time with the impact of therapies. The aim of this study is to determine if PD-L1 expression status changes in recurrent gliomas after chemoradiotherapy. Methods: Thirty eight patients with recurrent high grade gliomas who had surgical excision at least two times were included in this retrospective cross-sectional study. Nine patients were excluded because of the lack of appropriate pathology slides for pathologic evaluation. PD-L1 expression of 29 patients was evaluated by an expert pathologist with immunohistochemical methods. PD-L1 positivity was defined as expression in ≥1% of tumor cells. Change in PD-L1 expression status was defined as an absolute 5% difference between two resections. Results: Of the 29 patients, 15 patients (51.7%) had PD-L1 expression in ≥1% of tumor cells and 7 patients (24.1%) had PD-L1 expression in ≥10% of tumor cells. Tumor PD-L1 expression (defined as expression in ≥1% of tumor cells) was positive in 15 (51.7%) of 29 patients at diagnosis and at the time of recurrence. The PD-L1 status did not change in 17 patients (58.6%). 8 patients had PD-L1 negative tumors both at diagnosis and at recurrence, while 9 patients had PD-L1 positive tumors both at diagnosis and at recurrence. In 6 patients (20.7%) a negative-to-positive switch and in 6 patients (20.7%) a positive to negative switch were seen. Tumor PD-L1 expression increased in 7 of 29 patients (24.1%) and decreased in 9 of 29 patients (31.1%). PD-L1 expression remained stable in 13 of 29 patients (34.4%). The change in PD-L1 status over time was not statistically significant. Conclusions: More than 50% of high grade glial tumors express PD-L1 at diagnosis, so these tumors are good candidates for immune checkpoint inhibitors. The expression status changes in more than 40% of high grade glial tumors at recurrence, so immune responsiveness of glial tumors can be modified by treatments like chemotherapy and radiotherapy.
Experts issue guidelines for treating childhood brain injury
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Experts issue guidelines for treating childhood brain injury Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Trends in synchronous invasive ductal carcinomas of the breast: A SEER database analysis.
Authors: Rutika Jitesh Mehta, Adrienne Groman, Rohit K. Jain, Ellis Glenn Levine
Journal: Journal of Clinical Oncology (2017)

e13081 Background: Synchronous breast cancers are uncommon and account for around 2% of all breast cancer diagnosis. Lobular histology is considered a risk factor for synchronous breast cancers. We sought to study the trends in synchronous breast cancer of ductal histology and influence of age by interrogating the SEER database. Methods: The SEER Research data 1973-2013 was interrogated for synchronous infiltrating ductal carcinoma diagnosis (2 diagnosis within 6 months of each other). Overall survival (OS), the primary endpoint, was defined as the time (in months) from diagnosis to death from any cause. Univariate proportional hazards modeling results were used to assess the effect of age, race and stage on overall survival. All associations were considered statistically significant at an alpha error &lt; 0.01. All analyses were performed using SAS version 9.4. Results: 1469 cases were identified. Data was categorized by age group: ≤ 65 years or &gt; 65 years. 60% were 65 years or younger. 85% were Caucasians, 9.6% African Americans and 5.2% others. Younger women (≤ 65 years) had a statistically higher proportion of Stage III/IV breast cancer diagnosis as compared to older women (33.4% vs 25.2%; p = 0.002). The incidence rate of synchronous breast cancers has been rising since 1973, more pronounced in the older age group. Incidence rates overall have risen from 0.09/100,000 persons in 1973-1980 to 0.29/100,000 persons in 2001-2013 (p &lt; 0.001). Incidence rates for synchronous breast cancer in women &gt; 65 years has increased from 0.30/100,000 persons in 1973-1980 to 1.03/100,000 persons in 2001-2013. The adjusted OS among older women is significantly worse than that of younger women (HR 1.05; 95% CI 1.04-1.05; p &lt; 0.001). Conclusions: Better imaging techniques and breast cancer screening guidelines have likely improved breast cancer detection rates thus leading to a rise in the incidence of synchronous breast cancers. It can be speculated that underlying medical problems and advanced age result in more morbidity and subsequent mortality in older women with standard treatment. The finding of more advanced disease among younger women deserves scrutiny as to cause.
Diffuse Infiltrating Oligodendroglioma and Astrocytoma
Authors: Martin J. van den Bent, Marion Smits, Johan M. Kros, Susan M. Chang
Journal: Journal of Clinical Oncology (2017)

The new 2016 WHO brain tumor classification defines different diffuse gliomas primarily according to the presence or absence of IDH mutations ( IDH-mt) and combined 1p/19q loss. Today, the diagnosis of anaplastic oligodendroglioma requires the presence of both IDH-mt and 1p/19q co-deletion, whereas anaplastic astrocytoma is divided into IDH wild-type ( IDH-wt) and IDH-mt tumors. IDH-mt tumors have a more favorable prognosis, and tumors with low-grade histology especially tend evolve slowly. IDH-wt tumors are not a homogeneous entity and warrant further molecular testing because some have glioblastoma-like molecular features with poor clinical outcome. Treatment consists of a resection that should be as extensive as safely possible, radiotherapy, and chemotherapy. Trials of patients with newly diagnosed grade II or III glioma have shown survival benefit from adding chemotherapy to radiotherapy compared with initial treatment using radiotherapy alone. Both temozolomide and the combination of procarbazine, lomustine, and vincristine provide survival benefit. In contrast, trials that compare single modality treatment of chemotherapy alone with radiotherapy alone did not observe survival differences. Currently, for patients with grade II or III gliomas who require postsurgical treatment, the preferred treatment consists of a combination of radiotherapy and chemotherapy. Low-grade gliomas with favorable characteristics are slow-growing tumors. When deciding on the timing of postsurgical treatment with radiotherapy and chemotherapy, both clinical and molecular factors should be taken into account, but a more conservative approach can be considered initially in some of these patients. The factor that best predicts benefit of chemotherapy in grade II and III glioma remains to be established.