tbuckley/cabot-search huggingface dataset:
Abstract 2097: microRNA profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma
Authors: Jian-jun Zhao, Jianhong Lin, Tint Lwin, Hua Yang, Jianping Guo, William Kong, Sophie Dessureault, Lynn Moscinski, Dorna Rezania, William S. Dalton, Eduardo Sotomayor, Jianguo Tao, Jin Q. Cheng
Journal: Cancer Research (2010)

Abstract ABSTRACT: Mantle cell lymphoma (MCL) is one of the most aggressive B-cell lymphomas. While a number of protein-coding genes are altered, expression signature and importance of microRNA (miRNA) have not been well documented in this malignancy. Here, we performed miRNA expression profile in 30 patients with MCL using a platform containing 515 human miRNAs. Eighteen miRNAs were downregulated and 21 were upregulated in MCL when compared with normal B lymphocytes. The most frequently altered miRNAs are decrease of miR-29a/b/c, miR-142-3p/5p and miR-150 and increase of miR-124a and miR-155. Notably, expression levels of miR-29 family are associated with prognosis. The patients with significant downregulated miR-29 had short survival as compared to those who express relative high level of miR-29. Prognostic value of miR-29 is comparable with MIPI (MCL International Prognostic Index). Furthermore, we demonstrate miR-29 inhibition of CDK6 protein and mRNA levels by direct binding to 3′UTR. Inverse correlation between miR-29 and CDK6 was observed in MCL. Since cyclin D1 overexpression is a primary event and exerts its function through activation of CDK4/6, our results in primary MCL cells indicates that downregulation of miR-29 could cooperate with cyclin D1 in MCL pathogenesis. Thus, our findings provide not only miRNA expression signature but also a novel prognostic marker and pathogenetic factor for this malignancy. 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 2097.
Intense Skeletal Lesions in a Patient with Primary Hyperparathyroid Disease
Authors: M O Demirkol, H S Birinci, A Kadioğlu
Journal: Clinical Nuclear Medicine (2001)

ONUR DEMIRKOL, MEHMET M.D.,*; SEYMEN BIRINCI, HÜLYA M.D.†; KADIOĞLU, ALEV M.D.† Author Information
Multimodality Intravascular Imaging to Evaluate Sex Differences in Plaque Morphology in Stable CAD
Authors: Aditya S. Bharadwaj, Yuliya Vengrenyuk, Takahiro Yoshimura, Usman Baber, Choudhury Hasan, Jagat Narula, Samin K. Sharma, Annapoorna S. Kini
Journal: JACC. Cardiovascular imaging (2016)
SAT0412 Prediction of erosive disease in rheumatoid arthritis: Utility of ultrasound joint score in patients with a short disease duration
Authors: R. Osipyants, D. Karateev, E. Panasyuk, A. Smirnov, G. Lukina, S. Gluchova, E. Aleksandrova, A. Volkov, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> To optimize therapy in rheumatoid arthritis (RA) patients (pts), it would be beneficial to identify those pts who are going to suffer joint damage before X-ray - erosions occur, to allow more potent and expensive therapy to be targeted to those who would benefit most. Musculoskeletal ultrasound (US) is more sensitive than conventional radiography (CR) in the detection of erosive disease. <h3>Objectives</h3> We used a new US score of joint damage to identify whether changes seen in US examination of RA pts can predict of disease progression. <h3>Methods</h3> One hundred nine pts (85% women) with RA [median age 53 (range 45-58) years; disease activity score-28 (DAS28) 6.5 (5.5-7.0); 74% “+” for rheumatoid factor (RF) and 82% “+” for anti-citrullinated peptide antibodies (ACCP))] were enrolled. US examination (“Voluson-i” (GE, USA), 4-13 MHz probe) was performed by one examiner at baseline, 6 months. Erosions were scored for presence (break in cortical bone in two perpendicular planes: ≥2 mm in one plane, ≥1 mm in the second plane). An US score was developed to determine of bone erosions in the most affected joints included bilateral sum of 5 joints (0-10): the wrist, II-III MCP and II-III PIP joints (US-Er-10). Pts were difined as US progressing cases when the change (Δ) of the US-Er-10 &gt;1 units per 6 months. The van der Heijde-modified Sharp score (vdHSS) was calculated and other disease activity markers were measured. <h3>Results</h3> The progression of US score of bone damage was observed in 84 (77%) cases. Pts were divided into two groups according to ΔUS-Er-10 score: 1st group (n=24) – pts with ΔUS-Er-10 ≥3 (rapid US progression), 2nd (n=60) – with ΔUS-Er-10 &lt;3. We compared the changes seen in the US at 6 months with the X-ray erosion status at just 1 year. In subgroup RA pts with disease duration less two years Δ total vdHSS at one year [median 13.5 (range 3-23) vs. 0 (0-0) units, p&lt;0.029] and RF [278 (117-514) vs. 9.5 (0-168), p=0.019] were higher in those who had rapid US progression (n=10) than in other group (n=11).There were no significant differences in baseline US score or laboratory data and clinical disease activity markers between pts who developed progressive damage and those who did not. Meanwhile, in pts with disease duration &gt;2 years were not found significant associations between the change of US score of structural damage and follow-up X-ray – erosions. <h3>Conclusions</h3> This pilot study has shown a new US score (US-Er-10) to predict X-ray - erosive status in early-stageRA. The change in the US score may be used to target pts who require aggressive, expensive therapy. <h3>Disclosure of Interest</h3> None Declared
Progesterone for Traumatic Brain Injury — Resisting the Sirens' Song
Authors: Lee H Schwamm
Journal: New England Journal of Medicine (2014)

The results of two randomized, controlled trials of the neurosteroid progesterone in patients with traumatic brain injury (TBI), now published in the Journal, 1,2 showed no benefit with respect to favorable functional outcome at 6 months, as assessed by means of the Extended Glasgow Outcome Scale (GOS-E), or several prespecified secondary outcomes. Both trials selected and stratified patients on the basis of a Glasgow Coma Scale (GCS) score. The Study of a Neuroprotective Agent, Progesterone, in Severe Traumatic Brain Injury (SYNAPSE), conducted by Skolnick et al.,1 completed enrollment of 1195 participants with severe TBI, whereas the Progesterone for Traumatic Brain . . .
589 PATIENTS WITH MINIMAL HEPATIC ENCEPHALOPATHY SHOW IMPAIRED MISMATCH NEGATIVITY CORRELATING WITH REDUCED PERFORMANCE IN ATTENTION TESTS
Authors: V. Felipo, J.F. Ordoño, A. Urios, C. Gimenez-Garzo, O. Gonzalez, R. Giner, M.A. Serra, A. Wassel, J.M. Rodrigo, J. Salazar, C. Montoliu
Journal: Journal of Hepatology (2013)
Abstract 2701: Clinical implications of <i>UGT1A1*28</i> genotype testing in colorectal cancer patients
Authors: Katerina Shulman, Ilana Cohen, Ofra Barnett-Griness, Stephen B. Gruber, Flavio Lejbkowicz, Gad Rennert
Journal: Cancer Research (2010)

Abstract Purpose: Metastatic colorectal cancer is frequently treated with Irinotecan (CPT-11), a topoisomerase-I inhibitor. Irinotecan toxicity is relatively commonly observed. The gene UGT1A1 encodes an enzyme that catalyzes the glucuronidation of the active irinotecan metabolite SN-38 which is eliminated in the liver by metabolic alteration to an inactive form SN-38G. We retrospectively evaluated the association between UGT1A1 genetic variation, prevalence of severe toxicity and colorectal survival. Patients and Methods: In the Molecular Epidemiology of Colorectal Cancer (MECC) Study we identified 213 patients with metastatic colorectal cancer treated by irinotecan-based chemotherapy (FOLFIRI, IFL). DNA extracted from blood was used for genotyping either by simple determination of TATA box sequence in patient DNA or by implementation of fragment analysis that detects the difference in the number of nucleotides in the specific region analyzed. The polymorphism UGT1A1*28 is characterized by the presence of an additional TA repeat in the TATA sequence of the UGT1A1 promoter, ((TA)7TAA, instead of (TA)6TAA). Data on side effects and survival were extracted from full follow-up oncology records. Results: UGT1A1*28 genotypes 6/6, 6/7, 7/7 were detected in 41.8%, 46.5%, and 11.7% of the patients respectively. Observed grade 3-4 toxicity included: diarrhea 22.4%, leucopenia 9.3%, neutropenia 8.9%, neutropenic fever 3.7%, and mucositis 4%. No significant difference was observed in the rate of diarrhea in patients with UGT1A1*28 7/7 genotype (20%) as compared to these with the 6/6 genotype (27.5%). Hematological toxicity was significantly more common in patients with the 7/7 genotype. Neutropenic fever was observed in 24% of the 7/7 genotype but only in 2% of the 6/7 genotype and 0% of the 6/6 genotype. Oncological hospitalization rate was very high among the 7/7 group (45.8%) and significantly higher than among the 6/6 group (14.4%). The Median overall survival of patients with 7/7 was significantly lower (2.10 years) than that of patients with the 6/6 variant (4.13 years, p=0.002). Conclusion: UGT1A1*28 7/7 genotype is strongly associated with severe toxicity (mainly neutropenic fever) and oncological hospitalizations and with lower survival. These data support the FDA recommendation and product labeling to tailor treatment plans for colorectal cancer patients. 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 2701.
O2.04 * TREATMENT WITH OMX-4.80, A TUMOR-PENETRATING TUNABLE OXYGEN CARRIER, REDUCES TUMOR HYPOXIA AND DRAMATICALLY ENHANCES RADIATION THERAPY IN INTRACRANIAL MODELS OF GLIOBLASTOMA
Authors: A. Krtolica, N. Le Moan, L. Serwer, Y. Yoshida, T. Ozawa, N. Butowski, D. James, S. Cary
Journal: Neuro-Oncology (2014)

We have developed OMX-4.80, a tunable oxygen carrier from the H-NOX protein family, that preferentially accumulates in tumor tissue, reduces hypoxia and enhances radiotherapy (RT). Tumor hypoxia is associated with poor patient outcomes in multiple solid tumors including glioblastoma (GB) and is thought to be a major contributor to poor cancer responses to chemo and radiation therapy. Here, we show that OMX-4.80 administered i.v. into the tail vein of mice bearing orthotopic GB passes the blood-tumor barrier, penetrates deep into intracranial tumors, and significantly reduces tumor hypoxia in a dose-dependent manner. Hypoxia reduction is demonstrated by a significant decrease in levels of hypoxia inducible factor, HIF1α, and the external hypoxia marker pimonidazole as assessed by IHC and image analysis. Furthermore, hypoxia before and after treatment is compared in the individual tumors by concurrent immunostaining of tumors with a long-term hypoxia marker, Glut1, and short-lived HIF-1α. These data reveal >50% reduction in hypoxic tumor area after OMX-4.80 treatment confirming the effectiveness of OMX-4.80 in reducing hypoxia in individual tumors. When OMX-4.80 treatment was coupled with a single high dose of RT, we observed a 2.7-fold increase in tumor growth delay and 2.9-fold longer survival (p < 0.05, by logrank). Toxicology studies in rodents and dogs with single and multiple supratherapeutic doses of OMX-4.80 revealed a good safety profile affirming its suitability for clinical development. In conclusion, our results indicate that OMX-4.80 is an effective and promising RT enhancer that warrants clinical development in GB patients.
Abstract 4578: Deep targeted sequencing of 12 breast cancer loci in 4,700 women across four different ethnicities.
Authors: Sara Lindström, Brad Chapman, Gary Chen, Constance Chen, Akweley Ablorh, Loic Le Marchand, Brian Henderson, Oliver Hofmann, Daniel Mirel, Christopher Haiman, Peter Kraft
Journal: Cancer Research (2013)

Abstract Genome-wide association studies (GWAS) have identified multiple genetic loci associated with breast cancer risk. However, the underlying genetic structure in these regions is not fully understood and it is likely that the index GWAS signal originates from one or more yet unidentified causal variants within the region. We used next-generation sequencing to characterize 12 GWAS-discovered breast cancer loci in a total of 2,300 breast cancer cases and 2,300 controls across four ethnic populations. Study subjects were women from the Nurses’ Health Study (NHS) and the Multiethnic Cohort (MEC). Region intervals spanned between 46kb and 973kb and we hybrid-captured and sequenced a total of 5.5Mb. On average, we were able to capture 82% of the non-repetitive sequence in the targeted regions, and the average fraction of captured bases sequenced with a depth %gt20x was more than 95%. After single nucleotide variant (SNV) calling and quality control, a total of 138,898 SNVs remained for analysis. 87.4% of those had a minor allele frequency less than 0.5% and 50.2% were private mutations. Across all regions, a total of 81 SNVs showed evidence for association with breast cancer (P&amp;lt0.001) but we did not find unequivocal association evidence supporting a causal role for any individual SNV. However, in two of the regions (2q35 and 11q13), we were able to refine the GWAS signal and identify a high posterior probability (&amp;gt90%) set including less than 15 SNVs. We also conducted burden tests of rare variants (MAF&amp;lt0.005) but did not identify any significant associations after adjusting for number of tests. However, rare variants in FGFR2 and a second gene at 10q26 were nominally associated with breast cancer (P&amp;lt0.05). We are currently imputing existing breast cancer GWAS using this sequencing data as a reference panel which will triple our current sample size. These results stress the importance of large study samples when attempting to refine GWAS signals and illustrate the challenges facing post-GWAS fine-mapping studies. Citation Format: Sara Lindström, Brad Chapman, Gary Chen, Constance Chen, Akweley Ablorh, Loic Le Marchand, Brian Henderson, Oliver Hofmann, Daniel Mirel, Christopher Haiman, Peter Kraft. Deep targeted sequencing of 12 breast cancer loci in 4,700 women across four different ethnicities. [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 4578. doi:10.1158/1538-7445.AM2013-4578
GENDER DIFFERENCES IN LONG TERM SURVIVAL AFTER TRANS-CATHETER AORTIC VALVE REPLACEMENT IN PATIENTS WITH SEVERE AORTIC STENOSIS
Authors: Atish P. Mathur, Ahmed M. Abdel-Razek, Yulanka Castro Dominguez, Thomas Cocke, Pranaychandra Vaidya, Paul Andrews, Jock N. McCullough, Elie Elmann, Gabriele Di Luozzo, Tammy Russo, Joseph Parrillo
Journal: Journal of the American College of Cardiology (2015)
Abstract 5729: The Wnt transcription factor TCF4 mediates resistance of colorectal cancer cells to (chemo-) radiotherapy in a β-catenin-independent manner
Authors: Marian Grade, Christine Eimer, Georg Emons, Emil Kendziorra, Melanie Spitzner, Jochen Gaedcke, Hendrik Wolff, Tim Beissbarth, Thomas Ried, Tobias Pukrop, Michael Ghadimi
Journal: Cancer Research (2012)

Abstract Background: We recently demonstrated that the Wnt transcription factor TCF4 is over-expressed in rectal cancers that were resistant to preoperative chemoradiotherapy. Because the association between Wnt signaling and chemoradioresistance is a novel finding, we aimed to investigate whether this over-expression is functionally relevant. Methods: Three colorectal cancer cell lines were transfected with two shRNA-vectors targeting TCF4. Stable single-cell clone (SCC) populations were established, and selected clones were irradiated at 0, 1, 2, 4, 6 and 8 Gy. γH2AX staining was used to evaluate DNA double strand repair after irradiation, and changes in cell cycle distribution were analyzed before and after radiation. Finally, β-catenin activity was inhibited using both siRNAs and the small molecule inhibitor XAV939. Results: Silencing of TCF4 led to a significant radiosensitization in SW837 and SW480, whereas there was no effect in HT-29. Well-fitting, we observed significantly more γH2AX foci 24 hrs after radiation in SW837 SCCs compared to HT-29 SCCs, pointing to an impaired DNA damage repair in SW837. Furthermore, in SW837 SCCs, but not in HT-29 SCCs, we noticed a change in the cell cycle distribution towards radiosensitive cell cycle phases before radiation, and compromised cell cycle control after radiation. Finally, both siRNA- and small molecule-mediated inhibition of β-catenin activity did not influence the sensitivity to chemoradiotherapy. Conclusion: Our results indicate a novel mechanism through which the Wnt transcription factor TCF4 mediates chemoradioresistance in a β-catenin-independent manner. Moreover, they suggest that TCF4 is a potential molecular target to sensitize resistant tumor cells to (chemo-) radiotherapy. 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 5729. doi:1538-7445.AM2012-5729
Endoscopic ultrasound staging in gastric cancer: does it help management decisions in the era of neoadjuvant treatment?
Authors: W. Bohle, W. Zoller
Journal: Endoscopy (2012)

We read with great interest the article by Kutup et al. [1], which presented their somewhat disappointing results with endoscopic ultrasound (EUS) staging of gastric cancer. In particular, in half of their patients with locally limited disease, EUS staging would have resulted in overtreatment. Kutup et al. concluded that “the diagnostic accuracy of EUS in the clinical staging of gastric and cardia carcinoma is limited.”
La coagulation par le plasma d'Argon dans les rectites radiques chroniques hémorragiques
Authors: A Bousseloub, A Balamane, J Mammeri, F Belghanem, F Yahiaoui, W Menni, K Saidani, M Bensalem, N Sakhri, K Layaida, N Baiod, T Boucekkine
Journal: Endoscopy (2011)

Introduction: La Radiothérapie (RT) est une arme majeure du traitement des cancers pelviens. Sa complication principale est la Rectite Radique Chronique Hémorragique (RRCH). Il n'y a pas actuellement un consensus concernant le traitement de cette entité pathologique. La Coagulation par Plasma d'Argon (CPA), déjà utilisée dans le traitement d'autres lésions digestives hémorragiques, a été récemment proposée et utilisée dans les RRCH.
IMPACT OF CLINICAL FRAILTY ON VASCULAR FLOW RESERVE AFTER INFRAPOPLITEAL INTERVENTION IN PATIENTS WITH CRITICAL LIMB ISCHEMIA
Authors: Masashi Fukunaga, Kenichi Fujii, Kojiro Miki, Machiko Nishimura, Tetsuo Horimatsu, Ten Saita, Hiroto Tamaru, Sumiyoshi Akinori, Takahiro Imanaka, Masahiko Shibuya, Tohru Masuyama, Masaharu Ishihara
Journal: Journal of the American College of Cardiology (2015)
OP0189 Long term work disability in anti-TNF therapy treated patients with psoriatic arthritis: A population-based cohort study
Authors: L. Kristensen, M. Englund, P. Geborek, M. Neovius, J. Askling, L.T. Jacobsson, I. Petersson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Reduced work ability leading to sick leave is a common consequence of psoriatic arthritis (PsA). TNF-antagonist therapy has been a major advance in treating several aspects of PsA. Little is known about the impact of TNF treatment on long term work disability in PsA. <h3>Objectives</h3> To study proportions of long term sick leave and disability pension before and after TNF-antagonist therapy in PsA patients. <h3>Methods</h3> Using the population-based South Swedish Arthritis Treatment Group register, we identified 191 PsA patients (median age 43years, range 18-58y, 55% men), who between Jan 2003 and Dec 2007 (allowing for a complete 4 year follow-up period) started treatment with adalimumab, etanercept, or infliximab. We linked data to the payment register by the Swedish Social Insurance Agency and calculated the proportion on any sick leave in 30-day-intervals from 12 months before treatment start until 3 years after. For each PsA patient we randomly selected 4 reference subjects from the general population matched for age, sex, area of residence, and date of inclusion. <h3>Results</h3> At treatment initiation 67% of the PsA patients were either on sick leave or received disability pension of any degree from part time thru full time. During the first 12 months after treatment start this fraction dropped to 58%, and remained at 57% after 3 years (p&lt;0.001). Comparing PsA patients to the general population, the relative risk of being work disabled at treatment start, 12 months, and 3 years after treatment start was 4.2 (95% CI 3.4, 5.1), 3.7 (3.0, 4.5), and 3.4 (2.7, 4.2), respectively. Patients withdrawing from therapy during the follow-up period compared to patients sustaining treatment had the same baseline risk of being work disabled (69 vs 64%), but a 50% increased risk after the 3 year observational period (73 vs 53%; relative risk 1.5 [95% CI] 1.2, 1.8 for comparison between withdrawers to sustainers). <h3>Conclusions</h3> There is a decline in work disability during the first 12 months after initiation of TNF-antagonist treatment in PsA patients not explained by societal factors or secular trends. This decline was sustained for the following 3 years. Patients withdrawing from therapy have a 50% increased risk of being work disabled than patients remaining on therapy. <h3>Disclosure of Interest</h3> L. Kristensen Consultant for: Abbott, BMS, Pfizer, MSD, Mundipharma, M. Englund: None Declared, P. Geborek: None Declared, M. Neovius: None Declared, J. Askling: None Declared, L. Jacobsson Consultant for: Abbott, BMS, Pfizer, MSD, I. Petersson Consultant for: Abbott, Pfizer, MSD
Novartis Reply to the ATMOSPHERE Data Monitoring Committee
Authors: Gervais Tougas, R Paul Aftring
Journal: New England Journal of Medicine (2016)

To the Editor: The Sounding Board article by Swedberg and colleagues,1 now published in the Journal, describes the experience of the data monitoring committee of the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure (ATMOSPHERE) as data from other trials of aliskiren raised questions regarding a possible risk to participants in ATMOSPHERE.2 Novartis, as the sponsor of ATMOSPHERE, had engaged the independent data monitoring committee, which was composed of respected experts, to oversee the participants’ safety in this trial through periodic reviews of unblinded safety and efficacy data. During the course of the trial, the data monitoring committee, . . .