tbuckley/cabot-search huggingface dataset:
Abstract 686: MNK1 promotes the progression of breast ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC)
Authors: Qianyu Guo, Sonia V. del Rincon, Christophe Goncalves, Wilson H. Miller
Journal: Cancer Research (2016)

Abstract The mechanism by which breast ductal carcinoma in situ (DCIS) progresses to invasive ductal carcinoma (IDC) is poorly described. Previous studies have revealed that DCIS and IDC share similar genomes and transcriptomes. We hypothesize that one mechanism contributing to the DCIS to IDC conversion involves aberrations in mRNA translation. The Mnk/eIF4E axis has a critical role in promoting the translation of tumor promoting and pro-invasive mRNAs, thus we propose to study whether aberrant activation of this axis promotes the transition of DCIS to IDC. Our model system involved overexpressing constitutively active Mnk1 (caMNK1) in MCF10 variants: (1) MCF10A immortalized mammary epithelial cells and (2) MCFDCIS.com ductal carcinoma in situ cells (termed DCIS cells). Our in vitro results suggest that caMNK1 enables DCIS cells to gain invasive properties. First, overexpression of caMnk1 increased colony formation, larger acinar size in 3D culture, and promoted the migration and invasion of MCF10A and MCFDCIS cells. Second, SEL201, a novel Mnk1/2 inhibitor, can inhibit proliferation, colony formation, 3D acini formation, and the migration and invasion capacity of DCIS-pBABE and -caMNK1 expressing cells. Tumor xenografting in athymic nude mice revealed that caMNK1 facilitates the conversion of DCIS to IDC as the DCIS-caMNK1 expressing tumors progress to IDC, while DCIS-pBABE derived tumors retain DCIS-like structures. Breast tumor samples from patients with DCIS, IDC or mixed DCIS-IDC will also be obtained to examine the levels of phospho-Mnk1 and phospho-eIF4E. Citation Format: Qianyu Guo, Sonia V. del Rincon, Christophe Goncalves, Wilson H. Miller. MNK1 promotes the progression of breast ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 686.
A novel immunohistochemistry (IHC) algorithm for assigning cell of origin status in diffuse large B-cell lymphoma (DLBCL) that better predicts survival as compared to the Hans algorithm.
Authors: Kalyan Nadiminti, Michel Nasr, Sarah C Mott, Sergei Syrbu, Lori J. Rosenstein
Journal: Journal of Clinical Oncology (2014)

e19537 Background: DLBCL is a heterogenous disease in terms of outcome. Cell of origin is felt to be one of the most important predictors of outcome to therapy, with better outcome in germinal center B-cell-like (GCB) subtypes compared to non-GCB. Gene expression profiling (GEP) is the gold standard for determining cell of origin, however this is not widely available. Therefore, IHC algorithms have been developed as a surrogate to GEP in determining cell of origin. Several IHC algorithms have been reported, first by Hans et al. Later, refined by Choi, the algorithm incorporated new IHC markers such as GCET1. We report the use of a modified algorithm developed at our institution (UIHC), using IRF8 in place of GCET1, to predict overall survival (OS) and event free survival (EFS). Methods: A subset of UIHC pts (n=52) with DLBCL prospectively enrolled between 11/14/02 and 10/31/07 in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource were evaluated. Tissue sections were stained with antibodies against MUM-1, CD10, FOXP1, IRF8, and Bcl-6. Each case was classified as either GCB or non-GCB using both algorithms. Cox models were used to determine which algorithm better predicted OS and EFS. Results: Of the 52 pts, 37 were determined to have GCB phenotype using the UIHC algorithm compared to 30 with the Hans algorithm. Median follow up time for OS was 71.1 months. The OS rate was 44.2% (23/52). For non-GCB versus GCB, the hazard ratio (HR) for OS was 8.42 (95% CI 3.59- 19.75, P< 0.0001) using UIHC and 1.90 (0.83- 4.33, P= 0.123) using Hans. For EFS the HR was 3.8 (95% CI 1.83-8.16, P= 0.004) using the UIHC algorithm while it was 1.18 (95%CI 0.57-2.47, P=0.645) using Hans. Conclusions: As predicted, pts with non-GCB DLBCL had worse OS and EFS than those with GCB. However, this difference was only statistically significant when the UIHC algorithm was used. Thus, using a more specific germinal center marker such as IRF8 improved the predictive value of the algorithm. IRF8, a nuclear stain, is relatively easy to read and interpret which may aid in reproducibility. However, its role needs to be further studied in a larger population and compared to GEP.
PWE-016 Is there an increasing role for general anaesthetic during ercp?: Abstract PWE-016 Table 1
Authors: JS Leeds, U Basavaraju, A Mukhopadhya, MG Smith, A Fraser
Journal: Gut (2015)

<h3>Introduction</h3> ERCP remains an important diagnostic and therapeutic tool for the management of biliary and pancreatic diseases. In the UK this is mainly performed using conscious sedation but there appears to be an increasing need for deeper sedation and general anaesthesia. Since 2009 there has been a regular fortnightly list for provision of general anaesthetic to assist ERCP particularly for complex interventions in our unit. We report our experience of ERCP performed under general anaesthetic (GAERCP). <h3>Method</h3> Retrospective analysis of all patients who underwent ERCP in our centre was performed using the Unisoft reporting tool over the period June 2008 to December 2014. Patient demographics, indication for ERCP, indication for GA, complication rate and Cotton complexity scores were recorded. Trends in numbers of patients undergoing ERCP under GA, complications rates and complexity scores were calculated and comparison made to patients undergoing ERCP under sedation. <h3>Results</h3> Over the study period 2797 patients (1165 males, median age 69 years) under went ERCP of which 159 (5.7%) were under general anaesthetic. Those undergoing GAERCP were significantly younger than those having sedation (mean age 54.9 vs. 65.7 years, p &lt; 0.0001). Complexity scores were significantly higher in those undergoing GAERCP compared to sedation cases (median 3 vs 1, p &lt; 0.05). Over the study period total numbers of ERCP rose but proportionally GAERCP also significantly increased (1.3% in 2008 to 6.7% in 2014, p &lt; 0.001). Indications for GAERCP included previously failed (n = 38), patient preference/factors (n = 31), Spyglass (n = 28), pancreatic therapy (n = 19), biliary manometry (n = 17), complex stone disease (n = 11), ITU patient (n = 10), Bilroth II anatomy (n = 4), PSC with stricture (n = 1), ampullectomy (n = 1) and minor papilla procedure (n = 1). Successful completion rates at GAERCP improved from 75% in 2009 to 91.4% in 2014 (p = 0.019). Complication rate was 6.9% overall compared to 6.1% in the sedation group but the pancreatitis rate was higher (5.7% vs. 2.1%, p = 0.03) mainly in manometry patients. <h3>Conclusion</h3> There is an increasing need for ERCP under general anaesthetic particularly to cater for more complex and higher risk interventions. This can be achieved with a high completion rate but with a higher, but acceptable rate of post procedural pancreatitis. <h3>Disclosure of interest</h3> None Declared.
Effect of inflammation on prostate cancer incidence and dutasteride efficacy in the Reduction by Dutasteride of Cancer Events (REDUCE) study.
Authors: O. W. Brawley, G. L. Andriole, C. Teloken, M. C. Somerville, R. P. Gagnier
Journal: Journal of Clinical Oncology (2010)

4562 Background: REDUCE was a randomized, placebo-controlled 4-yr study of prostate cancer (PCa) risk reduction with 0.5 mg dutasteride daily. This analysis examines primary results of the REDUCE study by the maximum chronic inflammation (MCI) at baseline. Methods: Eligible men were aged 50–75 yrs, had serum PSA 2.5–10 ng/ml, and a single previous negative biopsy of 6–12 cores. Ten-core prostate biopsies were taken at 2 and 4 yrs. Chronic inflammation was categorized by a central pathology laboratory as none (0), mild (1), moderate (2) or marked (3) for each biopsy slide. MCI was the maximum score across the slides. Results: At baseline, of the 8193 subjects with chronic inflammation data available, 22% (n=1838) had no inflammation on biopsy, 69% (n=5656) had mild MCI, and 699 (9%) had either moderate or marked MCI (only 9 patients per treatment group had marked MCI). Subjects with no MCI had slightly higher mean PSA values and lower prostate volume (PV) at baseline (Table). The percentage of subjects with PCa overall, Gleason 7–10 PCa, and high grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation (ASAP) was higher in subjects with no inflammation. Dutasteride decreased overall PCa incidence and HGPIN/ASAP within each MCI category, and did not significantly increase the rate of Gleason 7–10 cancer in any MCI category. Conclusions: In the REDUCE study, the presence of inflammation in the baseline biopsy did not correlate with greater baseline PSA or increased incidence of PCa. Dutasteride reduced the risk of PCa, HGPIN and ASAP, regardless of the amount of inflammation on biopsy. REDUCE results by maximum chronic inflammation at baseline Parameter Treatment None (n = 1,838) Mild(n = 5,656) Moderate/marked(n = 699) Mean baseline age, yrs Pla 62.3 62.9 62.8 Dut 62.4 62.9 63.1 Mean baseline PSA, ng/ml Pla 6.08 5.88 5.78 Dut 6.01 5.91 5.64 Mean baseline PV, cc Pla 43.2 46.5 46.0 Dut 43.6 46.6 44.0 % PCa at 4 yrs Pla 31.7% 23.5% 20.4% Dut 25.6%** RRR = 20.7% 18.3%* RRR = 24.1% 17.3%*** RRR = 17.4% % Gleason 7–10 PCa at 4 yrs Pla 10.5% 5.9 5.5% Dut 9.5% 6.0% 4.6% % HGPIN and/or ASAP Pla 12.2% 10.8% 8.0% Dut 9.2% 7.0%* 7.1% * p < 0.0001, ** p < 0.01, *** p = 0.30 dutasteride vs. placebo. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline Aeterna Zentaris, EMD Serono, Ferring Pharmaceuticals, GenProbe, GlaxoSmithKline, Nema Steba, Onconome, sanofi-aventis, Veridex Amgen Cambridge Endo, Envisioneering Medical, GlaxoSmithKline, Viking Medical GlaxoSmithKline Aeterna Zentaris, GlaxoSmithKline, NCI, NIDDK
Abstract 2765: Asbestos exposure-related DNA methylation markers: a validation study in non-small cell lung tumors
Authors: Eeva Kettunen, Kristina Stuopelytė, Hector Hernandez-Vargas, Henrik Wolff, Sisko L. Anttila, Zdenko Herceg, Sonata Jarmalaite, Kirsti Husgafvel-Pursiainen
Journal: Cancer Research (2016)

Abstract Introduction. We have earlier explored the epigenome-wide DNA methylation in lung tumors. The study subjects, mostly smokers, consisted of lung cancer patients highly exposed to asbestos and those without exposure. We found methylation markers that associated either with sample type or exposure (asbestos or tobacco smoke) (Kettunen et al submitted). In this validation study, we focused on estimating the prevalence of the distinct methylation markers in a larger material of lung tumor patients with detailed exposure data available. Study design, subjects, and methods. We investigated the DNA methylation of selected markers in a validation set of 69 non-small cell lung cancer cases, tumor (T) and normal lung (N) from each. The patients, given a written informed consent, had been interviewed for detailed data on work and smoking history (as tobacco smoking pack-years, PY), and the pulmonary asbestos fiber counts quantified. Smoking-related methylation was studied in lung cancer groups of heavy-smokers (PYs higher than 36) vs lighter-smokers (PYs 36 or less) whereas methylation in asbestos-exposed lung tumor patients were compared with that in non-exposed lung tumor patients. DNA methylation was studied in tumor (T) and matched peripheral normal (N) lung tissue using pyrosequencing. Results. Numerous CpG positions in T vs N and eleven sites in asbestos-exposed tumors had indicated significant methylation variation (MVPs). Twenty-six differentially methylated positions (DMPs) having mean delta beta of at least 10% had been revealed in T vs N. Tobacco smoking- and asbestos exposure-related methylation sites were distinct, involving different CpG sites. We chose to validate five MVPs and four DMPs, both hypo- and hypermethylated CpG sites that were investigated using two instrumentation PSQ96MA and Pyromark Q24. The validation study set indicated good performance in pyrosequencing and we could demonstrate methylation of selected sites in relation to malignancy and exposure in this larger material. Conclusions. The central observations of the methylation showing distinct changes in relation to sample types and patients’ exposure status could be validated in a larger material. Significant methylation variation was observed in lung tumors. Citation Format: Eeva Kettunen, Kristina Stuopelytė, Hector Hernandez-Vargas, Henrik Wolff, Sisko L. Anttila, Zdenko Herceg, Sonata Jarmalaite, Kirsti Husgafvel-Pursiainen. Asbestos exposure-related DNA methylation markers: a validation study in non-small cell lung tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2765.
2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: Executive Summary
Authors: Glenn N. Levine, Eric R. Bates, James C. Blankenship, Steven R. Bailey, John A. Bittl, Bojan Cercek, Charles E. Chambers, Stephen G. Ellis, Robert A. Guyton, Steven M. Hollenberg, Umesh N. Khot, Richard A. Lange, Laura Mauri, Roxana Mehran, Issam D. Moussa, Debabrata Mukherjee, Brahmajee K. Nallamothu, Henry H. Ting
Journal: Circulation (2011)
Dual Specific Inhibitors Of The BCR-ABL and MNK Kinases As Potential Therapeutics For Blast Crisis Chronic Myeloid Leukemia
Authors: Sharon Lim, Joseph Cherian, Kassoum Nacro, Yun Shan Chew, Meng Ling Choong, Jun Ding Li, Samantha Guo, Melvyn Ho, Joma Joy, Perlyn Kwek, May Ann Lee, Boping Liu, Vithya Manoharan, Esther Ong, Vishal Pendharkar, Zhi Ying Poh, Anders Poulsen, Kanda Sangthongpitag, Kannan Srinivararaghavan, Siew Peng Tan, Haiyan Yang, Thomas H. Keller, Charles Chuah, S. Tiong Ong, Jeffrey Hill, Alex Matter
Journal: Blood (2013)
Biopsy transcriptome expression profiling to identify kidney transplants at risk of chronic injury: a multicentre, prospective study
Authors: Philip J O'Connell, Weijia Zhang, Madhav C Menon, Zhengzi Yi, Bernd Schröppel, Lorenzo Gallon, Yi Luan, Ivy A Rosales, Yongchao Ge, Bojan Losic, Caixia Xi, Christopher Woytovich, Karen L Keung, Chengguo Wei, Ilana Greene, Jessica Overbey, Emilia Bagiella, Nader Najafian, Milagros Samaniego, Arjang Djamali, Stephen I Alexander, Brian J Nankivell, Jeremy R Chapman, Rex Neal Smith, Robert Colvin, Barbara Murphy
Journal: The Lancet (2016)
Abstract 2938: Role of CD73 in promoting metastasis and resistance to 5-fluorouracil of colorectal cancer
Authors: Xuan-hui Liu, Xian-rui Wu, Yu-feng Chen, Feng-wei Wang, Xiao-bin Zheng, Dan Xie, Bo Shen, Jian-ping Wang, Xiao-jian Wu, Ping Lan
Journal: Cancer Research (2016)

Abstract Background and aim: Our previous study showed that high expression of CD73 (ecto-5’-nucleotidase) was a poor prognostic biomarker in patients with colorectal cancer (CRC). However, the underlying mechanism is unclear. Metastasis and chemo-resistance are among the main causes for the poor outcomes of CRC. The aim of this study is to evaluate the role of CD73 in the metastasis and chemo-resistance in CRC. Methods: The expression levels of CD73 were detected using quantitative RT-PCR and Western blot in 9 CRC cell lines and 3 5-FU-resistant cell lines (HCT8-FR, HCT116-FR, and RKO-FR). CD73 was overexpressed via lentiviral vector system and silenced using specific small interference RNA (si-CD73) in HCT8 and RKO. We then performed migration, invasion and MTS assays and wound healing assessment to evaluate the function of CD73 in cell progression and chemo-resistance. We conducted Cignal Finder Reporter Array to assess the main downstream signaling pathways of CD73. Results: Increased expression of CD73 was found in all 3 5-FU-resistant cell lines. Inhibition of CD73 expression in HCT8 and RKO by si-CD73 attenuated the capacity of cell migration and invasion but increased the sensitivity to 5-FU. On the other hand, overexpression of CD73 in HCT8 and RKO increased the capacity for cell migration but decreased the sensitivity to 5-FU. CD73-induced migration and chemo-resistance was found to be associated with the activation of MAPK/ERK pathway. Conclusions: High expression of CD73 was found to be associated with the metastasis and resistance to 5-FU via the activation of MAPK/ERK signaling pathway. This finding provides a molecular basis for the role of CD73 in the progression of CRC, suggesting a novel target for the treatment of CRC. Citation Format: Xuan-hui Liu, Xian-rui Wu, Yu-feng Chen, Feng-wei Wang, Xiao-bin Zheng, Dan Xie, Bo Shen, Jian-ping Wang, Xiao-jian Wu, Ping Lan. Role of CD73 in promoting metastasis and resistance to 5-fluorouracil of colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2938.
Autoimmune Thrombocytopenic Purpura Complicating Chronic Lymphocytic Leukemia: Analysis of 60 Patients.
Authors: Carlo Visco, Roberto Stasi, Marco Ruggeri, Achille Ambrosetti, Stefania Fortuna, Francesco Frattini, Ilaria Giaretta, Roberta Zanotti, Domenico Madeo, Giovanni Pizzolo, Francesco Rodeghiero
Journal: Blood (2006)
Demethylating Agents As a Salvage Treatment in Relapsed Myeloid Diseases Following Allogeneic Bone Marrow Transplantation
Authors: Sangeeta Atwal, Anjum Bashir Khan, Victor Noriega, Yogesh Jethava, Michelle Kenyon, Hugues de Lavallade, Donal McLornan, Victoria T Potter, Kavita Raj, Antonio Pagliuca, Ghulam J. Mufti
Journal: Blood (2012)
New Campaign to Focus on Physical Activity and Nutrition
Authors: Jennifer Abbasi
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Air Pollution Highest in World’s Poorest Cities
Authors: M. J. Friedrich
Journal: JAMA (2016)

In 98% of cities with populations greater than 100 000 in low- and middle-income countries, people are breathing air with pollution levels that exceed World Health Organization (WHO) safety limits, according to the latest WHO Global Urban Ambient Air Pollution Database (http://bit.ly/1XrMGm1).
Abstract 3824: Targeting MUC1-C oncoprotein inhibits AKT-S6K1-elF4A pathway regulated TIGAR translation in colorectal cancer
Authors: Rehan Ahmad, Maroof Alam, Omar Al-Obaid, Masanori Hasegawa, Donald Kufe
Journal: Cancer Research (2016)

Abstract Colorectal cancer is third most common malignancy and is the second most common cause of cancer-related death. The MUC1 multi-domain oncoprotein is aberrantly overexpressed in colorectal cancer and has been linked to poor outcomes in this disease. However, it is not known if MUC1 is of functional significance to colorectal tumors. Here, we investigate the effects of the MUC1-C inhibitor (GO-203), which disrupts MUC1-C homo-oligomerization, on AKT-mTORC-S6K translation pathway in human colorectal cancer cells. The present study demonstrates that GO-203 treatment was associated with inhibition of AKT-S6K1 signaling in colorectal cancer cells. Targeting MUC1-C with GO-203 downregulates TP53-inducible glycolysis and apoptosis regulator (TIGAR) protein. We show that GO-203-induced suppression of TIGAR is mediated by inhibition of AKT and the downstream mTOR pathway. The results also demonstrate that targeting MUC1-C blocks eIF4A cap-dependent translation of TIGAR. TIGAR promotes the shunting of glycolytic intermediates into the pentose phosphate pathway and thus is of importance for maintaining redox balance. In concert with these results, GO-203-induced suppression of TIGAR was associated with decreases glutathione levels. GO-203 treatment also resulted increases in reactive oxygen species (ROS) and loss of mitochondrial transmembrane potential. Consistent with these results, GO-203 inhibited the growth of colon cancer cells in vitro and xenografts in nude mice. These findings thus indicate that MUC1-C is a potential target for the treatment of colorectal cancer. Citation Format: Rehan Ahmad, Maroof Alam, Omar Al-Obaid, Masanori Hasegawa, Donald Kufe. Targeting MUC1-C oncoprotein inhibits AKT-S6K1-elF4A pathway regulated TIGAR translation in colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3824.
Random Plasma Glucose Levels and Cardiovascular Risk
Authors: Lijing L. Yan, Heng Jiang, Carolyn S. P. Lam
Journal: JAMA Cardiology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal