tbuckley/cabot-search huggingface dataset:
Endoscopically visualized features of gastric submucosal tumors on submucosal endoscopy
Authors: Hideki Kobara, Hirohito Mori, Shintaro Fujihara, Noriko Nishiyama, Johji Tani, Asahiro Morishita, Makoto Oryu, Kunihiko Tsutsui, Tsutomu Masaki
Journal: Endoscopy (2014)

Difficulties in the preoperative diagnosis of gastrointestinal submucosal tumors by endoscopic ultrasonography and errors of tissue sampling may make invasive surgery [1] or endoscopic resection [2] inappropriate for their removal. Better methods of diagnosing submucosal tumors are therefore needed. We have found that bloc biopsy and use of the submucosal endoscopy with a mucosal flap (SEMF) method [3] under direct vision can assist in the diagnosis of submucosal tumors [4] [5]. This method has the advantage of assessing the macroscopic characteristics of submucosal tumors. These endoscopically visualized features, identified by endoscopic imaging under direct view through a dissected submucosal tunnel, include the color, clarity, shape, and solidity of the tumor. Here, we describe the representative endoscopically visualized features of different types of gastric submucosal tumors.
OUTCOMES IN PATIENTS WITH POST-STRESS GLOBAL LEFT VENTRICULAR DYSFUNCTION (CARDIOMYOPATHIC RESPONSE) IN THE ABSENCE OF OBSTRUCTIVE CORONARY ARTERY DISEASE
Authors: Yader Sandoval, Daniel Davidovich, Charles Herzog, Bradley Bart, John C. Stendahl, Mengistu Simegn
Journal: Journal of the American College of Cardiology (2015)
Abstract 1336: Concurrent Snail expression and Kras mutation promote pancreatic fibrosis
Authors: Mario A. Shields, Mohammad WK Khan, Paul J. Grippo, Hidayatullah G. Munshi
Journal: Cancer Research (2012)

Abstract One of the hallmarks of pancreatic ductal adenocarcinoma (PDAC), the 4th leading cause of cancer related death in the US, is a pronounced collagen-rich stromal reaction. We recently published that type I collagen induces expression of Snail, a key regulator of epithelial-mesenchymal transition, to promote invasion and scattering of PDAC cells (Shields MA, et al. JBC 2011). To further understand the role of Snail in PDAC progression we generated transgenic mice expressing Snail in the pancreas. While there was robust Snail expression in the mouse pancreas, no phenotypic changes were observed. Since inflammation can promote Snail-mediated invasion and metastasis, we treated the Snail-expressing mice with cerulein to induce chronic pancreatitis. Although there was significant inflammation associated with vacuolization, no difference in the pancreatitis response was observed between control and Snail-expressing mice. Since Kras mutation has been shown to be necessary for tumor development in mouse models of pancreatic cancer, we generated mice expressing both mutant KrasG12D and Snail (Kras+/Snail+). Compared to control mice (Kras+/Snail-), Kras+/Snail+ mice developed significantly more acinar to ductal metaplasia, cystic papillary lesions that were associated with increased fibrosis, increased Smad2 and Stat3 phosphorylation. Experiments are underway characterizing the mechanism by which Snail promotes pancreatic fibrosis in Kras-expressing mice. 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 1336. doi:1538-7445.AM2012-1336
MS1-2: Tumor Entrained Neutrophils Inhibit Seeding in the Pre-Metastatic Lung.
Authors: Z Granot, E Heneke, EA Comen, TA King, L Norton, R Benezra
Journal: Cancer Research (2011)

Abstract Primary tumors have been shown to prepare distal organs for later colonization of metastatic cells by stimulating organ-specific infiltration of bone marrow derived cells. We have recently demonstrated that neutrophils are mobilized by the primary tumor and accumulate in the lung prior to the arrival of metastatic cells in mouse models of breast cancer. Tumor-entrained neutrophils (TENs) inhibit metastatic seeding in the lungs by generating H2O2 and tumor secreted CCL2 is both required and sufficient for optimal anti-metastatic entrainment of G-CSF-mobilized neutrophils. TENs are present in the peripheral blood of breast cancer patients prior to surgical resection but not in healthy individuals. Thus, while tumor-secreted factors contribute to tumor progression at the primary site, they concomitantly induce a neutrophil-mediated inhibitory process at the metastatic site. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr MS1-2.
ET-50 * LEVETIRACETAM DOWNREGULATES O6-METHYLGUANINE DNA METHYLTRANSFERASE EXPRESSION AND SENSITIZES TEMOZOLOMIDE-RESISTANT GLIOMA CELLS
Authors: N. Saito, K. Aoki, N. Hirai, M. Ishii, M. Tani, K. Sato, H. Nakayama, J. Harashina, H. Izukura, K. Ito, T. Sakurai, S. Iwabuchi
Journal: Neuro-Oncology (2014)

Temozolomide (TMZ) has become a key agent in treating malignant glioma; nevertheless, its survival benefit remains dismal prognosis. Histone deacetylases are often overexpressed in cancer cells, and this leads to altered expression and activity of numerous proteins involved in carcinogenesis. Recent evidence suggests that expression of class I histone deacetylases is higher in malignant gliomas and is important in resistance to TMZ. Levetiracetam (LEV) is an antiepileptic drug that inhibits histone deacetylases, but the therapeutic effects of a combination regimen comprising LEV and TMZ are poorly understood. In this study, we found that the antitumor effects of LEV are potentiated by combining it with TMZ, especially in TMZ-resistant cell lines. This combination significantly enhanced antitumor effects against the TMZ-resistant malignant glioma cell lines T98 and U138. This enhanced antitumor effect correlated with LEV-mediated reduction in O6-methylguanine DNA methyltransferase expression, which is important in cellular resistance to alkylating agents. In vitro, this combination enhanced apoptotic and autophagic cell death and suppressed migratory activities in the TMZ-resistant cell lines. Furthermore, an in vivo efficacy studies using an intracranial tumor model showed that combination therapy significantly increased median survival as compared with monotherapy groups. Our results warrant further studies to test the efficacy of combined TMZ and LEV chemotherapy in malignant glioma.
HG-02 * ATRX LOSS PROMOTES TUMOR GROWTH AND IMPAIRS GENETIC STABILITY IN GLIOBLASTOMA
Authors: C. Koschmann, A. Calinescu, D. Thomas, F. J. Nunez, M. Dzaman, J. Krasinkiewicz, N. Kamran, R. Lemons, F. Mendez, Y. Li, D. Ferguson, V. Gorbunova, S. Roh, L. Zhao, A. Meeker, P. R. Lowenstein, M. G. Castro
Journal: Neuro-Oncology (2015)

Pediatric glioblastoma (GBM) remains one of the most difficult childhood tumors to treat. ATRX is a histone chaperone protein that is mutated primarily in pediatric patients with GBM and younger adults with secondary GBM. No previous animal model has demonstrated the effect of ATRX loss on GBM formation. We cloned an ATRX knockdown sequence into a Sleeping Beauty (SB) transposase-responsive plasmid (shATRX) for insertion into host genomic DNA. Glioblastomas were induced by injecting plasmids encoding SB transposase/luciferase, shp53 and NRAS, with or without shATRX, into the lateral ventricle of neonatal mice. Tumors in both groups (with or without shATRX) showed histological hallmarks of human GBM. The loss of ATRX was localized only within tumors generated with the shATRX plasmid and not in the adjacent cortex. Notably, loss of ATRX significantly reduced median survival (p = 0.0032). Loss of ATRX in mouse GBM impaired genetic stability using multiple assays: (1) ATRX-deficient tumors were more likely to develop microsatellite instability, a hallmark of impaired DNA-damage repair; (2) ATRX-deficient tumors displayed evidence of telomeric lengthening, and (3) ATRX loss impaired non-homologous end-joining (NHEJ) utilizing a GFP reporter plasmid system. Analysis of human pediatric (St. Jude's/Washington University) and adult (UCSF) glioma datasets confirmed increased number of somatic nucleotide mutations in tumors with ATRX mutation. Finally, treatment of primary mouse GBM cell cultures showed that ATRX-deficient tumor cells were significantly more sensitive to certain DNA damaging agents, with greater evidence of double-stranded DNA breakage. In addition, mice with ATRX-deficient GBM treated with whole brain irradiation showed reduced early tumor growth by luminescence. This data demonstrates the role of ATRX in GBM tumor progression, treatment response and loss of tumor genetic stability, and provides a platform for future development of targeted therapy for pediatric and young adult patients with ATRX-deficient GBM.
Abstract 320: Association of higher Gleason grade with presence of PTEN deletion in prostatic adenocarcinoma
Authors: Maisa Yoshimoto, Andrew Evans, Joan Sweet, Olga Ludkovski, Keyue Ding, Greg Trottier, Kyu S. Song, Jeremy A. Squire
Journal: Cancer Research (2011)

Abstract Prostatic adenocarcinoma (CaP) is one of the most histologically heterogeneous of epithelial malignancies. The Gleason score is widely accepted as the standard for histologic grading and determining prognosis of prostate malignancies. The tumor often presents with a multifocal distribution though the gland and different Gleason grades may be present in different foci. The current study was undertaken to compare the association of genomic alterations with the Gleason grades of individual adenocarcinoma foci. Genomic deletion of the PTEN gene in routine formalin-fixed paraffin-embedded (FFPE) pathology sections can be readily assayed by fluorescence in situ hybridization (FISH). Data from our group and others has shown that the genomic deletion of the PTEN tumor suppressor gene and the disruption of the ETS gene family, play a central role in prostate cancer and are likely to be associated with Gleason grade. In this study CaP samples were thoroughly analyzed to identify PTEN heterogeneity, within or between foci in multifocal tumors. This study was designed to retrospectively assess the overall frequency with which PTEN deletions and TMPRSS2-ERG fusion rearrangements occur individually and simultaneously, and their clinical impact through FISH analysis using well-annotated high-throughput tissue microarrays (TMAs) derived from 128 patients with CaP. In addition, four-color FISH analysis of the PTEN deletion was used to precisely detect the interstitial deletion of genomic content from this region of chromosome 10q and evaluate the tumor heterogeneity. Genomic PTEN deletion was observed in 55 of 128 (43%) patients with CaP (hemizygous = 41 and homozygous = 14 CaP). TMPRSS2-ERG fusion was observed in 58 of 129 (45%). We specifically examined the relationship between PTEN deletion and TMPRSS2-ERG fusion status, Gleason pattern and clinical behavior of CaP. Importantly, PTEN deletions were significantly associated with a higher primary Gleason pattern grade 4 (p=0.000), lymphovascular invasion (p=0.051), and higher percentage of prostate involved by tumor (p=0.0064). Although TMPRSS2-ERG fusions showed a strong relationship with PTEN deletions (p=0.007), TMPRSS2-ERG fusions did not show any clinical correlation. In conclusion, our findings indicated that PTEN deletion FISH can be applied to CaP samples to accurately stratify patients into risk categories and to guide decision-making with respect to the optimal management of CaP patients. 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 320. doi:10.1158/1538-7445.AM2011-320
EUS Guided drainage of intraabdominal abscess - a new therapeutic window to left subphrenic space
Authors: N Rustemoviæ, M Opaèiæ, T Bates, R Ostojiæ, R Pulaniæ, B Vuceliæ
Journal: Endoscopy (2006)

Introduction: Surgery and percutaneous catheter drainage have been the main forms of treatment of the subphrenic abscess. Another treatment option that is potentially safe and effective is EUS-guided drainage. EUS provides excellent anatomic and vascular orientation because the diaphragm, the celiac trunk, and the splenic and paragastric vessels are being readily identified. One case is presented in which hard to reach subphrenic left sided abscess was successfully and safely drained under EUS guidance in critically ill patient.
Residents' Perspectives on ACGME Regulation of Supervision and Duty Hours — A National Survey
Authors: Brian C. Drolet, Lucy B. Spalluto, Staci A. Fischer
Journal: New England Journal of Medicine (2010)

The Accreditation Council for Graduate Medical Education has released new requirements for residents' supervision and duty hours. Surveyed residents predict the effects on their lifestyle, education, and preparation for supervisory roles, as well as patient safety.
A7.20 Low-dose ionising radiation inhibits adipokine induced inflammation in rheumatoid arthritis
Authors: K Shreder, A Cucu, L Deloch, B Frey, US Gaipl, M Durante, C Fournier
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints. For RA treatment, primarily drugs are used. However additional pain relieve is achieved when RA patients are treated either locally with low doses of sparsely ionising photons or by exposure to Radon. Main contributors to the inflammatory state in RA are adipokines, mainly produced by adipose tissue. To assess the effect of low radiation doses, we measured levels of adipokines in serum of patients with musculoskeletal diseases during Radon treatment. In additional <i>in vitro </i>experiments, we examined whether irradiation modifies the effects of recombinant adipokines on the expression of inflammatory and bone destructive factors in synovial fibroblasts (SF), key players in RA. <h3>Material and methods</h3> Serum samples were collected from patients before and after treatment with radon baths. Adipokine levels were measured by ELISA. Human SF from RA patients (RASF) and healthy donors (NSF) were pretreated with adipokines for 24h prior to irradiation with X-rays, and cell supernatants were collected after 24h to measure inflammatory factors known to contribute to the inflammatory process in RA (IL-6, IL-8, MMP-1). <h3>Results</h3> In the serum of patients, a significant decrease of the level of the adipokine visfatin was observed after therapy. The level of adiponectin was either reduced or unchanged, and no marked difference was observed for leptin. The results obtained <i>in vitro </i>using primary SF confirm the induction of proinflammatory factors by stimulation with adipokines. Irradiation of SF after treatment with adipokines, in turn, significantly reduces the expression of inflammatory factors. <h3>Conclusion</h3> Our data show for the first time a reduction of adipokine levels in serum of Radon treated patients. Since it is known that an elevated visfatin level positively correlates with serum levels of inflammatory factors IL-6 and CRP in RA patients, we hypothesise, that the decrease in serum visfatin level after low-dose irradiation affects the inflammatory process in the joint. Our <i>in vitro </i>results suggest the release of inflammatory factors after adipokine stimulation in both NSF and RASF can be reduced by low-dose X-ray irradiation, therefore potentially inhibiting inflammation in the joint of RA patients.
A4.02 Linking inhibition of chondrogenesis and inflammation through the smad linker domain
Authors: G van den Akker, H van Beuningen, E Vitters, E Blaney Davidson, P van der Kraan
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Cartilage repair using mesenchymal stem cells is a promising new strategy for the treatment of osteoarthritis. However, the inflammatory environment of the joint inhibits the repair process. Previously, it has been shown that signalling via transforming growth factor β family members is crucial for cartilage homeostasis. Therefore we evaluated the effect of inflammatory mediators on downstream mediators of TGFβ signalling: the R-SMAD transcription factors. <h3>Materials and methods</h3> Human mesenchymal stem cells were differentiated in monolayer or pellet cultures in chondrogenic differentiation medium. Differentiation was assessed at day 7 using GAG measurements. On day 3 of differentiation inflammatory stimuli were added. To determine the effect on TGFβ signalling the CAGA-luciferase reporter assay and immuno blotting for SMAD phospho-isoforms were used. A human phospho-kinase antibody array was performed to identify kinases activated by inflammation. <h3>Results</h3> Addition of IL1β and OAC-med to differentiating MSC at day 3, inhibited chondrogenic differentiation as measured by GAG deposition at day 7. Transcriptome analyses at 8 h post stimulation with inflammatory mediators revealed deregulation of TGFβ-related and regulated genes. TGFβ signalling was inhibited by inflammation as evidenced by inhibition of the SMAD3 dependant CAGA-luciferase reporter. SMAD2/3 activation by TGFβ is largely determined by C-terminal phosphorylation through the ALK5&nbsp;receptor. However C-terminal phosphorylation was not affected after addition of inflammatory stimuli. SMAD proteins contain a highly variable linker region that can be phosphorylated by various kinases. These linker modifications are known to modulate SMAD activation and degradation. Stimulation with either IL1β or OAC-med resulted in serine phosphorylation of the SMAD2 linker region within 1 h. To determine which kinase might be responsible for SMAD linker modification a human phospho-kinase antibody array was performed. The MAP kinase pathway was strongly activated within 30 min as evidenced by a &gt; 1.5 fold increase in pERK1/2 and pP38 compared to control pellets. <h3>Conclusions</h3> Inhibition of TGFβ signalling in differentiating MSC by IL1β and OAC-med appears to be mediated through SMAD serine linker modifications. The hot favourite kinases for phosphorylation of these serines are members of the MAP kinase family.
P2-01-15: RT-PCR Gene Profiling for the Prediction of Bone Metastases in Primary Breast Cancer.
Authors: T Ibrahim, L Mercatali, R Ricci, E Scarpi, C Liverani, L Serra, D Guerra, S Ciani, D Amadori
Journal: Cancer Research (2011)

Abstract Background: Patients with breast cancer frequently develop bone metastases, which are responsible for high morbidity and mortality. It is known that numerous molecules are involved in the bone metastasization process and that only cancer cells with a specific molecular profile are capable of reaching and colonizing bone tissue. The early detection of patients with a high probability of relapsing to bone could be used to select candidates for tailored therapy with bone-specific drugs such as bisphosphonates or RANK-L inhibitors. The aim of the present study was to identify a pattern of tissue markers from primary breast cancer capable of predicting bone metastatization. Material and methods: The expression of different markers was retrospectively analyzed in frozen breast cancer tissue samples from 40 patients comprising 15 cases with no evidence of disease (NEDP), 15 with bone metastases (BMP), and 10 with visceral metastases (VMP). Twelve transcripts were analyzed by Quantitative Real time PCR: trefoil factor 1(TFF1), DKK1, bone sialoprotein (IBSP), heparanase (HPSE), osteopontin (SPP1), Agr2, SPARC, CTGF, COMP, follistatin (FST), osteoprotegerin and RANK. The predictive accuracy of each marker was calculated using receiver operating characteristic (ROC) curves. Results: Analysis of marker expression in the 3 different subgroups showed twofold higher median values of COMP and HPSE in BMP with respect to either NEDP or VMP (no significant difference). Furthermore, TFF1 median value was about sevenfold higher in BMP than in the other 2 subgroups (p=0.05). The area under the curve (AUC) was 0.73 for TFF1 and 0.62 for COMP and HPSE. Considering markers as dichotomous variables, TFF1 expression in BMP reached 67% compared to 21% and 20% in NEDP and VMP, respectively. In dichotomous variable analysis, the most important result was observed for TFF1; in particular, TFF1 positivity was observed in 67% of cases in the BMP subgroup compared to only 21% and 20% in NEDP and VMP, respectively. The combination analysis of TFF1 and other markers showed that positivity to at least one of the three markers, TFF1, DKK1, or IBSP, was observed in 80% of cases for the BMP group, and in only in 21% and 20% of cases in NEDP and VMP subgroups (p=0.041). Another interesting marker was RANK: although sensitivity was fairly low (12%), specificity reached 100% in both control groups. Conclusions: Our preliminary study identified a RT-PCR gene expression pattern in primary breast cancer that could predict patients destined to bone relapse. Such patients could consequently benefit from adjuvant treatment with bone-targeted therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-15.
Ureterocele as a Cause of Abdominal Pain
Authors: Stuart L. Scheiner, Joseph Rogers, B. G. Clarke
Journal: New England Journal of Medicine (1955)

URETEROCELE, though not a common disorder, may be a perplexing diagnostic problem in adults. The present report concerns 5 cases in which the patients were treated unsuccessfully on the basis of mistaken or incomplete diagnosis of other conditions until urologic investigation disclosed ureterocele as the underlying disorder. In Case 1 the symptoms simulated those of inguinal hernia and the complications of its repair. In Case 2 pain caused by ureterocele was thought to be due to prostatovesiculitis. The symptoms of pyelonephritis in Case 3 could not be controlled until the obstructive lesion was diagnosed at cystoscopy. Another patient (Case 4) . . .
Late amendment to Care Bill "moves the goalposts" in fight over Lewisham Hospital, lawyer says
Authors: C. Dyer
Journal: BMJ (2013)

A last minute government amendment to the Care Bill will give trust special administrators who take over failing NHS trusts in England the power to recommend cuts and changes in services at neighbouring trusts and the health secretary the power to act on them.

The move came after a defeat in July for Jeremy Hunt, the health secretary for England, in a High Court case about Lewisham Hospital in southeast London.1

The amendment came just days before Hunt’s appeal against the judgment was due to go …