tbuckley/cabot-search huggingface dataset:
Détection assistée par ordinateur des lésions néoplasiques superficielles sur endobrachyoesophage
Authors: G. Rahmi
Journal: Endoscopy (2016)

La survenue d’un adénocarcinome sur endobrachyoesophage (EBO) est la principale complication redoutée lors de la surveillance endoscopique des patients. Actuellement les biopsies étagées systématiques selon le protocole de Seattle reste toujours recommandées même si la réalisation de biopsies ciblées sur des zones suspectes est de plus en plus courante compte tenu de l’évolution technologique des endoscopes proposant une image haute définition, un système de grossissement optique de plus en plus performant et la possibilité de réaliser une chromoendoscopie virtuelle en temps réel.
Abstract 224: The role of the microphthalmia associated transcription factor in autophagy regulation in melanoma
Authors: Katrin Moller, Sara Sigurbjornsdottir, Remina Dilixiati, Solveig H. Brynjolfsdottir, Lionel Larue, Vesteinn Thorsson, Eirikur Steingrimsson, Margret H. Ogmundsdottir
Journal: Cancer Research (2016)

Abstract Autophagy is considered a therapeutic target in various cancer types, including melanoma. The transcription factors TFEB and TFE3 have been shown to play a key role in autophagy regulation in various cell types by affecting gene expression required for this process. A close relative to these factors is the transcription factor MITF; often termed the master regulator of melanocyte development and function. MITF activity has also been shown to be important for various stages of melanoma formation and progression. Analysis of The Cancer Genome Atlas expression data from melanoma tumors reveals that MITF expression correlates with lysosomal and autophagy gene expression in metastatic tumors. Furthermore, analysis of expression data from 23 melanoma cell lines shows that MITF expression correlates with lysosomal and autophagy gene expression, and the analysis of available MITF ChIP sequencing data shows that MITF binds the promoters of lysosomal and autophagy genes. This binding was experimentally verified by ChIP experiments in 501Mel melanoma cells. MITF over-expression and knock down experiments show effects of MITF on lysosomal and autophagy gene expression, as well as an effect on the autophagy activity. Autophagy is high in melanoma and has been linked to tolerance against cancer treatment. We have found that MITF regulates autophagy genes and activity in melanoma cell lines. In light of both MITF and autophagy being considered a therapeutic target in melanoma, this relationship needs to be taken into consideration. Citation Format: Katrin Moller, Sara Sigurbjornsdottir, Remina Dilixiati, Solveig H. Brynjolfsdottir, Lionel Larue, Vesteinn Thorsson, Eirikur Steingrimsson, Margret H. Ogmundsdottir. The role of the microphthalmia associated transcription factor in autophagy regulation in melanoma. [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 224.
Comparison of IPSS and IPSS-R Scoring in a Population Based Myelodysplastic Syndromes (MDS) Study
Authors: Erica D. Warlick, Betsy A. Hirsch, Phuong L. Nguyen, Adina Cioc, Michelle A. Roesler, Rachel Fonstad, Jeffrey S. Miller, Daniel J. Weisdorf, Julie A. Ross
Journal: Blood (2012)
Use of XPF expression in tumors and XPF single nucleotide polymorphisms to predict clinical outcome in head and neck cancer.
Authors: A. E. Vaezi, X. Wang, S. C. Buch, D. Farrow, D. T. Weaver, A. D. D'Andrea, R. R. Seethala, M. Romkes, L. J. Niedernhofer, J. R. Grandis
Journal: Journal of Clinical Oncology (2010)

5520 Background: Platinum-based concurrent chemoradiotherapy is a prevailing treatment modality for locoregionally advanced head and neck squamous cell carcinoma (HNSCC). XPF is one subunit of the ERCC1-XPF endonuclease protecting against DNA damage induced by radiation or platinum compounds. Here, we developed a method to quantitatively measure XPF expression by immunohistochemistry in tumor samples and asked if it predicts clinical outcome in HNSCC treated with DNA damaging therapy. Methods: Monoclonal antibody (SPM228) specificity for XPF was determined using immunoblot, immunofluorescence, and immunohistochemistry. In a prospective cohort of 99 patients with non-recurrent HNSCC treated with platinum compound and/or radiation therapy, XPF protein expression was measured in tumor sections using automated quantitative immunohistochemistry with digital image analysis. XPF expression level was grouped into quartiles for evaluation of time to treatment failure (TTF) and overall survival using Kaplan-Meier survival estimators. XPF single nucleotide polymorphisms (SNPs) were determined and correlated with TTF. Results: Monoclonal XPF antibody (SPM228) demonstrated a high degree of specificity for XPF. Expression level of XPF was highly variable in HNSCC tumors and cell lines. In the cohort of HNSCC patients, low XPF expressers had better outcome (median TTF, 90 months) than intermediate and high expressers (median TTF, 29 months [p = 0.007] and 9 months [p=0.001], respectively). When the oropharyngeal cancer subset was examined separately, low XPF expression also correlated with better outcome (n=28, p = 0.022). High XPF expressers had consistently worse outcome both in oropharyngeal and non-oropharyngeal tumors. We identified one intronic XPF SNP that, when present, associated with shorter TTF (p=0.044) and increased XPF expression. Two other intronic XPF SNPs also correlated with shorter TTF, but not with XPF expression. Conclusions: Expression levels of XPF and SNPs in XPF correlate with clinical outcome to platinum-based genotoxic therapy and/or radiation therapy. In the future, XPF could be used as a biomarker to tailor therapy for individual HNSCC patients. No significant financial relationships to disclose.
Clinical performance, efficacy, and safety of the DigniCap system, a scalp-hypothermia system, in preventing chemotherapy (CTX)-induced alopecia in patients (pts) with early-stage breast cancer (BC).
Authors: A. Glencer, M. E. Melisko, L. Esserman, S. A. Melin, H. S. Rugo
Journal: Journal of Clinical Oncology (2011)

TPS244 Background: Scalp cooling prevents chemotherapy-induced alopecia by reducing the amount of drug delivered to scalp cells and by decreasing intra-follicular metabolic rate. Several devices exist and are in use world-wide. The most common use a series of gel caps that are time-consuming and cumbersome to use. The DigniCap is a free-standing system that utilizes a circulating coolant in a silicon-based cap and maintains a stable scalp temperature. More than 3200 patients have used this system in Europe, Russia and Japan. The majority were treated for breast or ovarian cancer. Overall success rate assessed by wig use is about 85% and varies by CTX regimen (Dignitana data on file). A review of 2000 patients found minimal toxicity (Breed WP, 2004). Scalp metastases are rare (0.6% in 1593 pts in 6 studies). Improved sense of wellbeing (quality of life and body image) has been documented among pts using scalp cooling (Van den Hurk, 2009). This study is a pilot study intended to evaluate the safety and efficacy of the DigniCap system in pts with BC receiving standard CTX at 2 centers in the US. Methods: Pts with stage I BC receiving CTX with either a taxane or an anthracycline are eligible. Scalp cooling begins 30 minutes prior to CTX and continues for up to 90 minutes after CTX; scalp temperature is maintained at 5C. Photographs of the hair/ scalp are taken at baseline, at each CTX cycle, and at 3, 6, and 12 months after end of CTX and will be quantitatively graded by a panel of independent reviewers blinded to CTX cycle. Pts will also quantitatively assess their hair loss during CTX. Toxicity, quality of life, body image, and impact of hair loss on treatment decisions will be assessed at baseline, during treatment, and at follow-up visits. A 20-patient feasibility study is currently enrolling with plans for a 100-pt pivotal trial. The feasibility study will be considered successful if fewer than 50% of enrolled pts discontinue DigniCap usage due to associated toxicity. 4 pts have been enrolled to date; 3 are in treatment, and one is in follow-up. Funding is by the Laszlo N Tauber Family Foundation and by Dignitana.
Abstract LB-068: Classification of cancer by synthesis of rare non-coding mutations within recurrent epigenetic and protein networks
Authors: Wei Zhang, Trey Ideker
Journal: Cancer Research (2016)

Abstract Cancers are mutationally heterogeneous, resulting in multiple subtypes with different clinical outcomes and responses to treatment. Newly available data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) working group have revealed vast numbers of mutations located in non-coding regions of the human genome. However, few of these mutations are recurrent and their functions are poorly characterized. Here, we synthesize all mutations identified in a patient, both coding and non-coding, in the context of prior knowledge of epigenetic architecture and molecular networks. Non-coding mutations are selected using a functional segmentation of the genome defined by the ENCODE, Roadmap, and FANTOM consortia; these are then aggregated with coding mutations using enhancer-gene (eQTL, HiC, Roadmap, linkage) and gene-gene functional interactions relevant to human cancer. This approach enables stratification of 756 patients from 22 cancer types into biologically and clinically informative subtypes, based on highly recurrent alteration of networks mediating cell adhesion, DNA damage checkpoint and apoptosis, HLA class I, PI3K signaling, telomere maintenance, or p53 signaling. Non-coding mutations (e.g. to enhancers of IKBKB, IL1A, and MALT1) are unified with coding mutations (e.g. in BTRC, ATM, and the PPAR subunits) within common networks, providing valuable prognostic power beyond the baseline survival rate of the tissue. We find that most of the relevant non-coding elements are affected in only one patient, with the recurrent signal becoming clear only after aggregation within epigenetic networks. Citation Format: Wei Zhang, Trey Ideker, the Pan-Cancer Analysis of Whole Genomes Working Group on Regulatory drivers and Pathways/Networks. Classification of cancer by synthesis of rare non-coding mutations within recurrent epigenetic and protein networks. [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 LB-068.
EGFR-related miRNAs as potential biomarkers of response to Erlotinib in metastatic NSCLC patients
Authors: M. Pagano, F. Zanelli, A. Bisagni, S. Maramotti, E. Tagliavini, S. Croci, R. Gnoni, G. Rossi, M. Paci, G. Sgarbi, A. Mozzarelli, A. Albini, G. Gardini, C. Boni
Journal: Annals of Oncology (2015)
Predictors of performing response monitoring in patients with chronic-phase chronic myeloid leukemia (CP-CML) in a prospective observational study (SIMPLICITY).
Authors: Stuart L. Goldberg, Jorge E. Cortes, Carlo Gambacorti-Passerini, Hanna Jean Khoury, Michael J. Mauro, Ronald Paquette, Bengt Simonsson, Aimee Foreman, Lawrence Rasouliyan, Hesham Mohamed, Milayna Subar, Teresa Maria Zyczynski
Journal: Journal of Clinical Oncology (2014)

116 Background: Previous SIMPLICITY data (ASCO 2014) have shown, in CP-CML patients (pts) with at least 12 months (mths) follow-up, monitoring for cytogenetic response (CyR) and molecular response (MR) differs from NCCN/ ELN recommendations and shows regional and practice-type variation. Few data describe predictors of monitoring. Methods: SIMPLICITY is an ongoing observational study of CP-CML pts receiving first-line (1L) imatinib (IM), dasatinib (DAS) or nilotinib (NIL) in the United States (US) and Europe (Eu); its primary objective is to understand tyrosine kinase inhibitor (TKI) management patterns in clinical practice (NCT01244750). Frequency of testing for CyR, by FISH or karyotype, and MR, by PCR, were analyzed in 3, 6 and 12 mth increments from TKI start. Stepwise multivariable logistic regression was performed to assess predictors of monitoring (including: age, sex at birth, region, practice type, 1L TKI, ECOG performance status, still on 1L TKI). Results: 1,083 pts (US: 66%; Eu: 34%) were enrolled prospectively through 1Apr2014, receiving IM (n=415), DAS (n=343) or NIL (n=325). 1,050, 985 and 862 pts were followed for at least 3, 6 and 12 mths, respectively. Of these, 15%, 34% and 49% were tested for CyR, and 27%, 65% and 83% were tested for MR, between 0–3 mths, 0–6 mths and 0–12 mths. By 3 mths, 33% had either CyR and/or MR testing and 88% of pts underwent testing by 12 mths. None of the candidate predictors distinguished between pts who were monitored vs. those that were not by 3 mths after start of 1L TKI. Pts &lt;65 years (yrs) at start of 1L TKI (odds ratio [OR]=1.41) and those in Eu vs. US (OR=1.45) were more likely to be monitored by 6 mths. By 12 mths, pts &lt;65 yrs (OR=2.27), those no longer on 1L TKI (OR=1.96), and those seen in academic centers (OR=1.59) were more likely to be monitored (all p&lt;.05). A comparison of monitoring patterns with ELN/NCCN recommendations will also be presented. Conclusions: Two-thirds of pts were not monitored for CyR or MR within 3 mths of TKI start.Although there were no predictors of monitoring for CyR or MR by 3 mths, age &lt;65 yrs at initiation of 1L TKI was a consistent predictor of monitoring by 6 and 12 mths. Clinical trial information: NCT01244750.
Biomarker Proteasome Levels Predict Response to Combination Therapy with Carfilzomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients
Authors: Neha Korde, Talib Dosani, Olga Simakova, Sham Mailankody, Rene Costello, Mark Roschewski, Constance Yuan, Maryalice Stetler-Stevenson, William D Figg, Ola Landgren, Irina Maric
Journal: Blood (2014)
β-Defensin 2 is a responsive biomarker of IL-17A–driven skin pathology in patients with psoriasis
Authors: Frank Kolbinger, Christian Loesche, Marie-Anne Valentin, Xiaoyu Jiang, Yi Cheng, Philip Jarvis, Thomas Peters, Claudio Calonder, Gerard Bruin, Florine Polus, Birgit Aigner, David M. Lee, Manfred Bodenlenz, Frank Sinner, Thomas Rudolf Pieber, Dhavalkumar D. Patel
Journal: Journal of Allergy and Clinical Immunology (2016)

IL-17A is a key driver of human autoimmune diseases, particularly psoriasis.We sought to determine the role of IL-17A in psoriasis pathogenesis and to identify a robust and measurable biomarker of IL-17A-driven pathology.We studied 8 healthy subjects and 8 patients with psoriasis before and after administration of secukinumab, a fully human anti-IL-17A mAb, and used a combination of classical techniques and a novel skin microperfusion assay to evaluate the expression of 170 proteins in blood, nonlesional skin, and lesional skin. For validation, we also tested stored sera from 601 patients with a variety of autoimmune diseases.IL-17A was specifically expressed in lesional compared with nonlesional psoriatic skin (9.8 vs 0.8 pg/mL, P < .001). Proteomic and gene transcription analyses revealed dysregulated antimicrobial peptides, proinflammatory cytokines, and neutrophil chemoattractants, levels of which returned to normal after treatment with secukinumab. β-Defensin 2 (BD-2) was identified as a biomarker of IL-17A-driven pathology by comparing protein expression in patients with psoriasis versus that in healthy subjects (5746 vs 82 pg/mL in serum, P < .0001; 2747 vs <218 pg/mL in dermis, P < .001), responsiveness to secukinumab therapy, and synergistic induction by IL-17A and TNF-α in epidermal keratinocytes. In a validation set of sera from 601 patients with autoimmune diseases thought to be IL-17A driven, we found that BD-2 levels are most highly increased in patients with psoriatic skin lesions, and in patients with psoriasis, BD-2 levels correlated well with IL-17A levels (r = 0.70, n = 199, P < .001) and Psoriasis Area and Severity Index scores (r = 0.53, n = 281, P < .001).IL-17A is a primary driver of skin pathology in patients with psoriasis, and serum BD-2 is an easily measurable biomarker of IL-17A-driven skin pathology.
Abstract 1333: Bigelovin inhibits colorectal cancer by suppressing the growth and inducing apoptosis bothin vitroandin vivo
Authors: Ming-Yue Li, Grace Gar-Lee Yue, Stephen Kwok-Wing Tsui, Kwok-Pui Fung, Ning-Hua Tan, Clara Bik-San Lau
Journal: Cancer Research (2016)

Abstract Colorectal cancer (CRC) is one of the most common cancers with high incidence and mortality worldwide. In 2014, CRC was the second commonest cancer and second leading cause of cancer deaths in Hong Kong. National Cancer Institute estimates that 132,700 people will be diagnosed with CRC and 49,700 people will die from the disease in 2015 worldwide. Despite effectiveness of the chemotherapeutics, severe side effects often affect patients’ normal life. Traditional Chinese medicines can be a good source of anti-tumor agent with better safety profile. Here, we reported a sesquiterpene lactone (bigelovin) isolated from Inula helianthus- aquatica, which was shown to induce anti-angiogenesis1 and apoptosis2 in vitro. Although previous studies reported its apoptotic effects on various cell lines, there were no detailed mechanistic or animal studies on its effect on colon cancer cells. To further explore its effect on CRC, we used both in vitro and in vivo assays. The effects of bigelovin in vitro were determined by Annexin V/PI double staining, cell cycle assay and western blotting. Bigelovin was shown to have better selectivity in colon cancer cells than primary normal colon cells. Besides, CRC cells treated with bigelovin resulted in decrease in cell proliferation and increase in apoptosis in both time- and dose-dependent manner. Western blot results also showed caspase activation and protein changes of key molecules (p-H2A.X-DNA damage marker, Cyclin B1-cell cycle, etc). Furthermore, bigelovin (20 mg/kg) significantly reduced the growth of CRC cells-driven tumors in vivo without severe side effects comparing to FOLFOX (containing folinic acid, 5-fluorouracil and oxaliplatin) treatment. Taken together, these results suggested that bigelovin can be a promising therapeutic candidate for colorectal cancer. References: 1. Yue, G.G.L., et al. Anti-angiogenesis and immunomodulatory activities of an anti-tumor sesquiterpene bigelovin isolated from Inula helianthus-aquatica. Eur J Med Chem, 2013, 59: 243-52. 2. Zhang, H.H., et al. Bigelovin inhibits STAT3 signaling by inactivating JAK2 and induces apoptosis in human cancer cells. Acta Pharmacol Sin, 2015, 36(4): 507-16. Citation Format: Ming-Yue Li, Grace Gar-Lee Yue, Stephen Kwok-Wing Tsui, Kwok-Pui Fung, Ning-Hua Tan, Clara Bik-San Lau. Bigelovin inhibits colorectal cancer by suppressing the growth and inducing apoptosis both in vitro and in vivo. [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 1333.
Oxygen metabolism and barrier regulation in the intestinal mucosa
Authors: Louise E. Glover, J. Scott Lee, Sean P. Colgan
Journal: Journal of Clinical Investigation (2016)

Mucosal surfaces are lined by epithelial cells and provide an important barrier to the flux of antigens from the outside. This barrier is provided at a number of levels, including epithelial junctional complexes, mucus production, and mucosa-derived antimicrobials. Tissue metabolism is central to the maintenance of homeostasis in the mucosa. In the intestine, for example, baseline pO2 levels are uniquely low due to counter-current blood flow and the presence of large numbers of bacteria. As such, hypoxia and HIF signaling predominates normal intestinal metabolism and barrier regulation during both homeostasis and active inflammation. Contributing factors that elicit important adaptive responses within the mucosa include the transcriptional regulation of tight junction proteins, metabolic regulation of barrier components, and changes in autophagic flux. Here, we review recent literature around the topic of hypoxia and barrier function in health and during disease.
Abstract P158: Systematic Review and Meta-analysis of Acute Effects of Alcohol Consumption on Risk of Cardiovascular Events
Authors: Elizabeth Mostofsky, Harpreet S Chahal, Kenneth J Mukamal, Eric B Rimm, Murray A Mittleman
Journal: Circulation (2016)

Introduction: Although considerable research describes the cardiovascular effects of habitual moderate and heavy alcohol consumption, the acute risks following alcohol intake have not been well characterized. Based on its physiological effects, alcohol may have markedly different effects on acute and long-term risk. We assessed the hypothesis that moderate alcohol consumption is associated with an immediately higher risk of cardiovascular events that becomes protective after 24 hours, whereas heavy alcohol drinking is associated with higher cardiovascular risk both immediately and in the following days. Methods: We searched CINAHL, Embase, PubMed and PsycINFO from inception to March 12 2015, supplemented with manual screening for observational studies assessing the association between alcohol intake and cardiovascular events in the following hours and days. We calculated pooled relative risks (RRs) and 95% confidence intervals (CIs) for the association between alcohol intake and myocardial infarction (MI), ischemic stroke (IS) and hemorrhagic stroke (HS) using DerSimonian and Laird random-effects models to model any alcohol intake or dose-response relationships of alcohol intake and cardiovascular events. Results: Among 1056 citations and 37 full-text articles reviewed, 23 studies (29457 participants) were included. Moderate alcohol consumption was associated with an acutely higher cardiovascular risk that was attenuated after 24 hours and even protective for MI and HS (≈2-4 drinks: RR=30% lower risk), and protective against IS within one week (≈6 drinks: RR=19% lower risk). In contrast, heavy alcohol drinking was associated with higher cardiovascular risk in the following day (≈6-9 drinks: RR=1.3-2.3) and week (≈19-30 drinks: RR=2.25-6.2). Conclusions: In conclusion, there appears to be a consistent finding of an acutely higher cardiovascular risk following any alcohol consumption but by 24 hours, only heavy alcohol intake conferred continued risk.