tbuckley/cabot-search huggingface dataset:
CSIG-03INTEGRATING COMPUTATIONAL AND EXPERIMENTAL APPROACHES TO UNDERSTAND THE SMG1 KINASE NETWORK IN GLIOBLASTOMA STEM CELLS
Authors: Sejuti Sengupta, Steven K. Young, Surbhi Goel-Bhattacharya, Brent H. Cochran
Journal: Neuro-Oncology (2015)

The SMG1 kinase was identified and validated from an RNAi screen as a gene that can preferentially inhibit the growth of selected glioblastoma stem cell lines under hypoxia (1% oxygen). In addition, we have found that SMG1 knockdown can substantially enhance the inhibitory effects of the DNA damaging drug, temozolomide (TMZ), both in vitro and in mouse xenografts. In order to evaluate the relative contributions of nonsense mediated decay, the DNA damage response (DDR), and autophagy in the cellular response to SMG1 inhibition, we have used the Cell Collective software platform (BMC Systems Biology, 6, 96) to model the SMG1 signaling network. To do this, we integrating our data with results in the literature in order to simulate the cell growth and survival of GBM stem cells under hypoxia and TMZ induced DNA damage. Our model initially predicted that the preferential growth inhibition of SMG1 inhibition in GS7-2 cells under hypoxia specifically was likely due to the role of NMD pathway in regulating autophagy. We tested the model-generated hypothesis and found induction of the autophagy marker, LC3-II, when SMG1 is knocked down under hypoxia. However, either inhibition of autophagy-related protein, ATG7, or inhibition of NMD pathway does not fully account for the preferential growth inhibition by loss of SMG1 under hypoxia. We have refined the model based on these results and are currently testing the prediction that a defect in the DDR pathway accounts for growth inhibition when SMG1 is knocked down under hypoxia. Our preliminary results indicate greater DNA damage, possibly leading to cell cycle block, when SMG1 is knocked down under hypoxia. The long-term goal of this study will be to develop therapeutic predictions for targeting SMG1 and other kinase targets in a given tumor and in order to develop personalized therapies for GBM.
Mini direct cholangioscopy and direct targeted bile duct biopsies using a laser fiber through a biliary catheter
Authors: J. Ramesh, C. Wilcox, K. Mönkemüller
Journal: Endoscopy (2013)

Cholangioscopy has improved our ability to study diseases of the biliary tract and to provide therapy [1] [2]. A prerequisite for cholangioscopy using available systems is the presence of common bile duct dilation and a previous sphincterotomy [1] [2]. We present a modified technique for performing cholangioscopy in patients with a stenosed common bile duct and/or intact papilla.
QL-06 * RELIABILITY OF THE SF-36 QUESTIONNAIRE FOR ASSESSMENT OF HEALTH RELATED QUALITY OF LIFE IN NEUROSURGICAL BRAIN TUMOR PATIENTS
Authors: A. Bunevicius, S. Tamasauskas, V. P. Deltuva, A. Tamasauskas, R. Bunevicius
Journal: Neuro-Oncology (2014)

BACKGROUND: Brain tumor is often a devastating disease associated with significant impairment of health-related quality of life (HRQoL). We evaluated reliability of the SF-36 questionnaire for assessment of HRQoL in neurosurgical brain tumor patients. METHODS: Consecutive patients admitted for primary brain tumor surgery were considered for this prospective study. On admission, patients were evaluated for HRQoL (SF-36 scale), functional status (Barthel index or BI) and depressive symptom severity (Beck depression inventory-II or BDI-II). RESULTS: Two-hundred and fourteen patients (70% women and 30% men; mean age 55.8 ± 14.4 years) completed the study. The most common brain tumor diagnoses were meningioma (40%), high-grade glioma (18%) and pituitary adenoma (13%). The lowest scores were on the SF-36 General health (48.3 ± 20.0), Role limitations due to physical problems (53.2 ± 42.5) and Energy/vitality (53.7 ± 21.5) subscales. Internal consistency of individual SF-36 subscales was acceptable for all but Social functioning subscale of the SF-36 questionnaire with Cronbach's coefficients alpha ranging from 0.92 for Physical functioning subscale to 0.69 for General health subscale of the SF-36. There was a moderate-to-strong correlation of the Role limitations due to emotional problems, Energy/vitality and Emotional well-being SF-36 subscales with the BDI-II scores (Pearson's correlation coefficients r range from -0.30 to -0.66; p-values <0.001). Scores on the SF-36 Physical functioning and Role limitations due to physical problems correlated with BI scores (0.49 and 0.25, p-values <0.001). CONCLUSIONS: In neurosurgical brain tumor patients, the greatest impairment was found in General health, Role limitations due to physical problems and Energy/vitality domains of HRQoL. The SF-36 subscales had acceptable internal consistency with an exception of Social functioning subscale. The SF-36 subscales pertaining to physical health and emotional health aspects of HRQoL demonstrated adequate construct validity. The SF-36 is a reliable measure of HRQoL in neurosurgical brain tumor patients.
Abstract 3741: Adjuvant active specific immunotherapy improves survival of patients with micro-satellite stable colorectal tumors, but not with micro-satellite instable tumors
Authors: Vincent A. de Weger, Zelda Euler, Harm van Tinteren, Herman Bril, Gerrit A. Meijer, Erik Hooijberg
Journal: Cancer Research (2010)

Abstract Purpose: It has been documented that Active Specific Immunotherapy (ASI), given as adjuvant treatment, improves survival of patients with stage II and III colorectal cancer (CRC). Here we report on the effects of ASI on Micro-Satellite Stable (MSS) versus Micro-Satellite Instable (MSI) tumors. Materials and Methods: From 196 patients with stage II or stage III CRC who previously participated in the ASI trial published previously (Vermorken et al. Lancet), we collected frozen tumor samples and/or paraffin embedded tumor material. From this material DNA was extracted and microsatellite stability status was assessed. Microsatellite status was associated with clinical outcome in both the placebo and ASI treatment groups using Kaplan Meier analysis. Results: From 196 patients participating in the trial we retrieved good quality archival tumor DNA for further analysis of microsatellite stability (MS). We subsequently identified 162 (83%) MSS tumors and 34 MSI (17%) tumors. Irrespective of MS status a significant survival benefit for patients receiving ASI treatment (P=0.012) was observed, confirming previous results. New to this is that irrespective of treatment, patients with MSI tumors showed significantly less recurrences than patients with MSS tumors (P = 0.03). Taking both MS status and treatment into account we found no significant difference in survival between ASI treated versus placebo receiving patients with MSI tumors. In contrast, patients with MSS tumors benefited from ASI treatment showing a significantly improved recurrence free survival (P=&amp;lt;0,05). Conclusion: It can be concluded that only patients with MSS tumors will benefit from adjuvant ASI since only they showed significant improved recurrence free survival on ASI therapy. For the MSI group there is most likely no benefit of ASI therapy. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 3741.
The Renormalization of Smoking? E-Cigarettes and the Tobacco “Endgame”
Authors: Amy L. Fairchild, Ronald Bayer, James Colgrove
Journal: New England Journal of Medicine (2013)

Whereas some experts welcome e-cigarettes as a pathway to reducing tobacco use, others characterize them as dangerous products that could undermine efforts to denormalize smoking. But the goal of eliminating the risks of smoking is not incompatible with e-cigarette use.
P234 Training Deficiencies and Lack of Confidence Around Knowledge in Primary Care Nurses Treating Asthma and COPD Patients
Authors: AG Davison, L Jongepier
Journal: Thorax (2012)

<h3></h3> There has been an increasing shift of respiratory care from secondary to primary. We have undertaken a training needs analysis by questionairre of primary care nurses who treat patients with Asthma and COPD in all 511 practises in the East of England. 63% responded. Nurses were asked to grade their confidence levels from high (5) to low (1) in aspects of Asthma and COPD. Chi-square was used for statistical analysis. <h3>Results</h3> ASTHMA. 63% had a diploma. 90% followed BTS/SIGN guidelines. There was a high confidence level in 27% for differential diagnosis, 52% for inhaler devices and how to use them, 24% for interpretation of spirometry, 39% for emergency treatment, 22% for dealing with children 5–12 years old. High confidence was significantly greater (&lt;0.001) in those with an asthma diploma. COPD. 35% had a diploma. 82% followed NICE or GOLD guidelines. 76% ran clinics. There was a high confidence in 37% diagnosis, 37% for management and monitoring, 26% for interpreting spirometry, 32% in emergency treatment. High confidence was significantly greater in those with a COPD diploma. Nurses were asked if they were aware of services and confident how to refer; 94% were for smoking cessation, 55% for spirometry, 35% for oxygen assessment, 63% for pulmonary rehabilitation. The level of awareness was significantly higher for the latter two in those with a diploma. ONGOING TRAINING OPPORTUNITIES Nurses were asked where and how often training was accessed on a scale 1–5. The most frequent (5) was self-directed learning in 37% and from the pharmaceutical industry 17%; the least (1) were time to learn 46%, monitoring with a practice expert 45%, secondary care provider 43%. <h3>Conclusions</h3> This study has revealed serious deficiencies in training with many having no diploma. The benefit of having a diploma is shown in greater confidence in knowledge and in awareness of services and how to refer. On-going professional education is haphazard. If increasing care is going to be successfully transferred into primary both these issues must be addressed.
AB0932 Hypertrophic Cutaneous Lupus Erythematosus: A Diagnostic Pitfall
Authors: N.M. Walsh, P.J. Green, J.G. Hanly
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Hypertrophic cutaneous lupus erythematosus (HCLE), an uncommon variant of discoid lupus erythematosus (DLE), is a challenging diagnosis. Its clinical presentation as verrucous nodules or markedly hyperkeratotic plaques on the extensor surfaces of the extremities and/or the face, and accompanying histopathological features simulate squamous cell carcinomas and actinic keratoses. <h3>Objectives</h3> We studied our collective experience of this rare entity over the past decade, to establish whether existing awareness of its challenging nature is sufficient to avert medical error. <h3>Methods</h3> Patients with HCLE were identified via clinical records in Rheumatology and Dermatology and cross referenced with those in Pathology. Demographic, clinical and pathological data were reviewed. <h3>Results</h3> Seven patients [2 men and 5 women] with HCLE were identified. The mean age was 49 years (range 30-61). In 4 patients with systemic lupus erythematosus (SLE), 3 had previously documented DLE and were under the care of a dermatologist and/or a rheumatologist. The remaining 3 patients were managed by plastic surgeons. The hyperkeratotic nodules and plaques of HCLE were located on the face in 4 cases and on the extremities in 3. Biopsies were undertaken in 5 cases because of a clinical suspicion of malignancy and in 2 due to diagnostic uncertainty. In 3 patients an erroneous clinical and pathological diagnosis was made prior to recognition of HCLE: 2 were diagnosed with squamous cell carcinomas in the perioral area resulting in inappropriate surgery; the other was diagnosed with psoriasis. <h3>Conclusions</h3> In this series from an academic medical centre there was a failure to recognize and appropriately treat HCLE in 3 of 7 patients upon initial presentation. Despite cautionary evidence in the literature, HCLE continues to elude diagnosis, thereby leading to delayed medical intervention or inappropriate surgery. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2260
Preoperative Assessment of Patients with Known or Suspected Coronary Disease
Authors: Dennis T. Mangano, Lee Goldman
Journal: New England Journal of Medicine (1995)

Cardiovascular disease is the leading cause of death in the United States, Canada, Europe, and Japan.1,2 Of the 27 million patients who undergo surgery in the United States each year, approximately 8 million have coronary artery disease or risk factors for cardiovascular disease; 1 million have perioperative cardiac complications, which result in approximately $20 billion in annual costs for in-hospital and long-term care.3 Over the next several decades, furthermore, the effects of the aging of the population will exacerbate the problem; more than 37 million patients will undergo surgery each year in the United States, of whom 40 percent . . .
Abstract P2-06-23: A New Way To Determine Multifocality: The Use of Molecular Markers?
Authors: G Werkoff, M Antoine, A Rodenas, J Gligorov, J Chopier, S Uzan, R. Rouzier
Journal: Cancer Research (2010)

Abstract AIM: Multifocality in breast cancer has a great on treatment options. However, the prevalence of multifocality is currently underestimated at the time of diagnosis because of the lack of sensitivity of clinical examination and imaging. Our aim was to develop a tool for predicting multifocality based on clinical and immunohistochemical criteria. METHOD: This study was conducted at Tenon Hospital with samples from patients operated on between 2002 and 2009. We constructed a tissue micro-array (TMA) from 100 breast specimens: 50 multifocal tumors and 50 unifocal unifocal tumors. Unifocal tumors were matched with multifocal tumors by size of largest focus, hormonal receptor status and SBR grade. These unifocal controls had either a mastectomy or a pre-operative MRI to rule out occult multifocality. We studied the expression of ten different antibodies (HER2, KI67, CK 5/6, CK 14, CK18, Vimentine, C-kit, EGFR, p53, and p63). From the results of this analysis we developed a prediction model based on a multivariate logistic regression. RESULTS : For the proteins tested, the concordance of immunohistochemical staining of foci from multifocal tumors ranged from 72% to 100%. In the univariate analysis, only c-kit expression was significantly associated with multifocality (P&amp;lt;0.05). The discrimination (area under the ROC curve) of a multivariate model based on clinical, pathological, and immunohistochemical variable was good (0.72) but lacked robustness when tested by internal validation. CONCLUSION: We report the first clinico-biological predictor of multifocality. New markers are currently tested to improve the performance of the multivariate model. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-23.
Terminal Ileitis with Obstruction and Abscess Complicating Pregnancy
Authors: William W. Babson
Journal: New England Journal of Medicine (1946)

IT IS the purpose of this paper to report and discuss a patient with cicatrizing ileitis, accompanied by obstruction and abscess, who was observed during the seventh month of pregnancy.Regional ileitis is the most frequent chronic inflammatory disease of the small bowel and its mesentery. After Crohn1 directed attention to this disease in 1932, sufficient operative cases had been reported by 1939 to allow Shapiro2 to tabulate 519. Its occurrence in a severe form during pregnancy, however, has not been reported in the literature. Intestinal obstruction is also an unusual complication of pregnancy. Hansen,3 in 1941, noted 84 cases . . .
A Phase I Open-Labelled, Single-Arm, Dose-Escalation, Study of Dichloroacetate (Dca) in Patients with Advanced Solid Tumours
Authors: Q.S. Chu, R. Sangha, J. Spratlin, L.J. Vos, J.R. Mackey, A.J.B. McEwan, P. Venner, E.D. Michelakis
Journal: Annals of Oncology (2014)
Abstract B30: Altered response to the prodrug of gemcitabine LY2334737 by overexpression or knockdown of carboxylesterase 2 (CES2)
Authors: Sara Durland-Busbice, Susan E. Pratt, Robert L. Shepard, Philip W. Iversen, Lisa Kays, Darryl Ballard, Kathleen Heinz-Taheny, Anne H. Dantzig
Journal: Clinical Cancer Research (2010)

Abstract Gemcitabine (gem) is a nucleoside anticancer agent that inhibits cell cycle in S-phase and is registered clinically for the treatment of a number of solid tumors. A prodrug of gemcitabine, LY2334737, was developed for oral administration for metronomic dosing with the aim of growth inhibition of more tumor cells as they go through the cell cycle. LY is well absorbed and systemically cleaved in humans. The rate of hydrolysis is slow resulting in circulating levels of LY that are 10-fold higher than gemcitabine in plasma. Studies with cell lines and recombinant protein indicate that LY is cleaved to gemcitabine by carboxylesterase 2 (CES2). Because LY circulates in the plasma for an extended period of time, we wondered if expression of CES2 by the tumor could alter its response to the prodrug. The present study was undertaken to determine if the expression of CES2 alters cellular response to LY in vitro and in vivo. The constitutive expression of CES2 in SKOV-3 was knocked down by shRNA. A stable subclone was obtained that had CES2 expression reduced by 80%. Stable HCT-116 transfectants were prepared that overexpressed CES2. Cell lines, transfectants and knock down cells were evaluated for drug sensitivity in a cytotoxicity assay. They were also evaluated for CES2 expression by biochemical cellular assay, Western analysis, and qRT-PCR. A xenograft study was conducted employing transfected HCT-116 cells. Immunohistochemical (IHC) staining was used to evaluate cell lines and tumors for CES2 expression. LY was less cytotoxic to SKOV-3 cells when CES2 was knocked down while sensitivity to gem was unaltered. Transfection of CES2 into low CES2 endogenously expressing HCT-116 cells enhanced LY drug sensitivity with no change in gemcitabine sensitivity. Stably transfected CES2 and mock HCT-116 transfectants were grown as a xenograft. The transfectants had identical growth rates in vivo and were equally sensitive to gem treatment. IHC staining of the tumors indicated that CES2 expression was maintained throughout the growth period. CES2 expressing tumors demonstrated a statistically significant greater response to LY than mock transfectant tumors. Taken together, these studies indicate that CES2 cleaves the prodrug and tumor expression of CES2 can enhance response to treatment with LY2334737. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B30.
Abstract 4770: TNFα and IFN-γ cooperate to up-regulate Fas expression to sensitize human colon carcinoma cells to Fas mediated apoptosis
Authors: Kankana Bardhan, Kebin Liu
Journal: Cancer Research (2011)

Abstract Fas (also known as CD95) is a member of the tumor necrosis factor (TNF) superfamily that mediates the extrinsic apoptosis signaling pathway when engaged by its physiological ligand FasL. Although the Fas death receptor has been shown to initiate cellular proliferation and survival signal pathways in certain tumor cells uder certain conditions, it is generally believed that under physiological conditions Fas functions as a guardian against not only autoimmunity but also other disease including cancer. Fas is highly expressed in normal human colon epithelial cells but is often down-regulated in human colorectal carcinoma, whereas complete loss of Fas expression is often observed in metastatic human colorectal carcinoma. These observations thus suggest that colon carcinoma cells might use loss of Fas expression and/or function to acquire an apoptosis resistant phenotype to advance the disease. Therefore, re-activating Fas expression might be an effective approach to sensitize the human colon carcinoma cells to apoptosis to suppress tumor development. In this study, we demonstrated that there exist CpG islands in the human Fas promoter region and inhibition of DNA methylation up-regulates Fas expression in metastatic human colon carcinoma cells, resulting in increased tumor cell sensitivity to Fas-mediated apoptosis. However, bisulfite DNA sequencing revealed that there are just a few methylated CpGs in the human Fas promoter region in metastatic human colon carcinoma cells, suggesting that DNA methylation mediates Fas expression indirectly. On the other hand, TNFα and IFN-γ, when used in combination, dramatically up-regulated Fas expression level in the metastatic human colon carcinoma cells. Up-regulation of Fas by TNFα and IFN-γ also resulted in sensitization of the metastatic colon carcinoma cells to Fas-mediated apoptosis. Our data thus suggest that re-activation of the death receptor Fas might be an effective approach to enhance the efficacy of Fas-based therapy against metastatic human colon cancer. 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 4770. doi:10.1158/1538-7445.AM2011-4770
913 THE ASSOCIATION BETWEEN SUSTAINED VIROLOGICAL RESPONSE AND BASELINE LOW-DENSITY LIPOPROTEIN CHOLESTEROL LEVELS IN THE TREATMENT OF CHRONIC HEPATITIS C PATIENTS WITH GENOTYPE 1
Authors: N. Tuna, N. Ozgunes, S. Celik, F. Sirmatel, N. Ince, S. Tosun, A.C. Utku
Journal: Journal of Hepatology (2013)
P0775 : Final evaluation of 955 HCV patients treated with 12 week regimens containing sofosbuvir +/- simeprevir in the trio network: Academic and community treatment of a real-world, heterogeneous population
Authors: D. Dieterich, B. Bacon, S. Flamm, K. Kowdley, S. Milligan, N. Tsai, Z. Younossi, E. Lawitz
Journal: Journal of Hepatology (2015)