tbuckley/cabot-search huggingface dataset:
Immunotherapy in allergic rhinitis and lower airway outcomes
Authors: V. Cardona, O. Luengo, M. Labrador-Horrillo
Journal: Allergy (2016)

Allergic rhinitis and asthma constitute two clinical expressions of a single-condition, respiratory allergy. Allergen immunotherapy (AIT) is a form of treatment specifically aimed at modifying the response to sensitizing allergens. The inherent potential benefit of AIT is the simultaneous treatment of all clinical expressions of respiratory allergy. Current data support the effectiveness of subcutaneous and sublingual immunotherapy in rhinitis. Studies also provide proof for a beneficial effect in allergic asthma. Even more, substantial evidence points to the preventive effect on the progression from rhinitis to asthma. Despite the current knowledge on the basic mechanisms underlying the immunological effect of AIT is vast, the specific mechanisms for the preventive effect of primary sensitization or new sensitizations are poorly understood. This review aimed to provide a critical overview of the current knowledge on the effectiveness of AIT and its potential role in secondary prevention of respiratory allergy progression.
Comparative Gene Expression Analysis of Mouse and Human Cardiac Maturation
Authors: Hideki Uosaki, Y-h Taguchi
Journal: Genomics Proteomics & Bioinformatics (2016)

Understanding how human cardiomyocytes mature is crucial to realizing stem cell-based heart regeneration, modeling adult heart diseases, and facilitating drug discovery. However, it is not feasible to analyze human samples for maturation due to inaccessibility to samples while cardiomyocytes mature during fetal development and childhood, as well as difficulty in avoiding variations among individuals. Using model animals such as mice can be a useful strategy; nonetheless, it is not well-understood whether and to what degree gene expression profiles during maturation are shared between humans and mice. Therefore, we performed a comparative gene expression analysis of mice and human samples. First, we examined two distinct mice microarray platforms for shared gene expression profiles, aiming to increase reliability of the analysis. We identified a set of genes displaying progressive changes during maturation based on principal component analysis. Second, we demonstrated that the genes identified had a differential expression pattern between adult and earlier stages (e.g., fetus) common in mice and humans. Our findings provide a foundation for further genetic studies of cardiomyocyte maturation.
Genetic/Familial High-Risk Assessment: Colorectal Version 1.2016, NCCN Clinical Practice Guidelines in Oncology
Authors: Dawn Provenzale, Samir Gupta, Dennis J. Ahnen, Travis Bray, Jamie A. Cannon, Gregory Cooper, Donald S. David, Dayna S. Early, Deborah Erwin, James M. Ford, Francis M. Giardiello, William Grady, Amy L. Halverson, Stanley R. Hamilton, Heather Hampel, Mohammad K. Ismail, Jason B. Klapman, David W. Larson, Audrey J. Lazenby, Patrick M. Lynch, Robert J. Mayer, Reid M. Ness, Scott E. Regenbogen, Niloy Jewel Samadder, Moshe Shike, Gideon Steinbach, David Weinberg, Mary Dwyer, Susan Darlow
Journal: Journal of the National Comprehensive Cancer Network (2016)

This is a focused update highlighting the most current NCCN Guidelines for diagnosis and management of Lynch syndrome. Lynch syndrome is the most common cause of hereditary colorectal cancer, usually resulting from a germline mutation in 1 of 4 DNA mismatch repair genes (MLH1, MSH2, MSH6, or PMS2), or deletions in the EPCAM promoter. Patients with Lynch syndrome are at an increased lifetime risk, compared with the general population, for colorectal cancer, endometrial cancer, and other cancers, including of the stomach and ovary. As of 2016, the panel recommends screening all patients with colorectal cancer for Lynch syndrome and provides recommendations for surveillance for early detection and prevention of Lynch syndrome-associated cancers.
Abstract 1702: Sucrose nonfermenting 1-related kinase (SNRK) expression in ovarian cancer and correlation with clinical features
Authors: Elizabeth E. Hopp, Erin Bishop, Stephanie Cossette, Ramani Ramchandran
Journal: Cancer Research (2016)

Abstract Objective: Human omental adipocytes promote migration and invasion of ovarian cancer cells and result in alterations in metabolism including increased AMP-activated protein kinase (AMPK) and b-oxidation, which allow for use of lipids as an energy source. Sucrose nonfermenting 1-related kinase (SNRK) is a member of the AMPK family of serine/threonine kinases, which are activated by starvation and stress conditions. The goal of this study is to describe the expression of SNRK in human ovarian cancer tissue. Methods: Tissue was collected from patients undergoing surgery for serous ovarian cancer or benign indications. Immunohistochemistry (IHC) was used to detect SNRK expression. SNRK+ cells were compared between benign and malignant tissue, and statistical significance between positivity and clinicopathologic variables was determined using the Mann-Whitney U test. Results: In the 31 samples analyzed, SNRK demonstrates a nuclear staining pattern. IHC shows increased SNRK+ cells in malignant tissue versus benign tissue (42.0% versus 31.3% positive nuclei, p&amp;lt;0.001). When examining patient characteristics, the malignant samples with the lowest percentage of SNRK+ nuclei were stage IIIB-IV with a high incidence of recurrence and death due to disease. Conclusions: This is the first study to describe SNRK expression in ovarian cancer tissue. We show that SNRK has a nuclear staining pattern and that expression is greater in malignant ovarian tissue compared to benign ovarian tissue, which may be due to more metabolic stress on cells with higher proliferation rates. SNRK expression appears to be lower in those with a higher disease stage and poor outcome potentially secondary to metabolic changes that occur once the disease metastasizes. We are currently examining SNRK expression in metastatic omental tumors in order to further explore expression differences between primary versus metastatic disease sites. Citation Format: Elizabeth E. Hopp, Erin Bishop, Stephanie Cossette, Ramani Ramchandran. Sucrose nonfermenting 1-related kinase (SNRK) expression in ovarian cancer and correlation with clinical features. [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 1702.
Treatment of Generalized Deep Morphea With Everolimus
Authors: Laure Frumholtz, Jennifer Roux, Martine Bagot, Michel Rybojad, Jean-David Bouaziz
Journal: JAMA Dermatology (2016)

adenosine diphosphate receptors.Ticagrelor is a cyclopentyltriazolo-pyrimidine and reversibly binds adenosine diphosphate receptors.Up to 6% of patients taking clopidogrel will develop an allergy, which usually manifests as a pruritic morbilliform eruption but may also present with angioedema, fixed drug eruption, Stevens-Johnson syndrome (SJS), serum sickness-like reaction, or a systemic inflammatory response syndrome (SIRS). 2,3Similar allergic reactions have been reported to ticagrelor and prasugrel but are less well defined, given these drugs' limited use to date. 5,6 Patients who develop an allergy to their antiplatelet therapy must continue antiplatelet therapy or risk in-stent thrombosis and death.Therefore, strategies to manage these allergies and prevent drug cessation are imperative.Two large case series with 91 combined patients have shown success with "treating through" the clopidogrel allergy with prednisone taper and antihistamines, with a small minority of patients requiring repeat prednisone tapers and no patients requiring drug cessation. 2,3A 3-week prednisone taper starting at 30 mg twice daily for 5 days followed by a decrease of 5 mg/d every 3 days for 15 days resulted in 98% clearance and no recurrence of symptoms. 2Similar strategies have been used in cases of prasugrel and ticagrelor allergy. 5,6 This strategy should not be used for patients with severe allergic responses, including SJS and SIRS.Rather, in this subset of patients, switching to the alternative antithrombotic class (ie, thienopyridine or cyclopentyltriazolo-pyrimidine) is recommended.In conclusion, in patients with mild and moderate allergic reactions to antiplatelet therapy after cardiac stenting, antiplatelet therapy should be continued to prevent in-stent thrombosis, and the allergy may be treated with a 3-week taper of prednisone.
Benign pleural nodules in a patient with esophageal cancer
Authors: Wan Teck Lim, Ramaswamy Govindan
Journal: Journal of Clinical Oncology (2006)

tologous RBC scan demonstrated multiple foci of uptake corresponding to the CT findings, suggesting splenosis (Fig 2). A repeat CT scan 2 years later showed no interval change in the pleural masses. Thoracic splenosis is the rare autotransplantation of splenic tissue intrathoracically following traumatic splenic injury. Functional imaging with radiolabeled RBCs is a noninvasive method of diagnosis that may be utilized instead of biopsy. The appearance on the CT images, as in this case, can be confused with metastatic tumor nodules. As the presence of pleural metastasis may affect treatment decisions in the setting of localized disease, thoracic splenosis should be considered in the differential diagnosis in patients with cancer, pleural nodules, and a history of splenic injury.
Implementation of Watson Genomic Analytics processing to improve the efficiency of interpreting whole genome sequencing data on patients with advanced cancers.
Authors: Takahiko Koyama, Steven Jones, Filippo Utro, Yussanne Ma, Kahn Rhrissorrakrai, Yaoqing Shen, Boaz Carmeli, Martin Jones, Zeev Waks, Erin Pleasance, Raquel Norel, Richard Moore, Erhan Bilal, Andrew J. Mungall, Kirk Beaty, Jacquie Schein, Vanessa Vincenzi Michelini, Marco Marra, Ajay Royyuru, Janessa J. Laskin
Journal: Journal of Clinical Oncology (2015)

e12549 Background: The personalized onco-genomics project (POG) at BCCA uses paired tumour/normal whole genome and transcriptome sequence information from a cancer patient to inform treatment options. Analysis and interpretation of this large and complex data set is difficult to complete within a clinically relevant time-frame of less than 10 days. As whole genome sequencing becomes more accessible there is a need to scale-up these interpretive processes but maintain a high degree of evidence and data integrity. We compare the analytic output of conventional human literature review and data compilation with that of Watson Genomic Analytics (WGA). Methods: The POG has biopsied, sequenced and analyzed over 100 metastatic cancers since 2012. Each case has whole genome and transcriptome sequencing and the data is mined to identify somatic mutations or disrupted signaling cascades that might be functionally critical for understanding driver events within an individual's cancer or useful for rationalizing treatment planning. Anonymized data from 29 cases was input into WGA system which reads mutation, copy number and gene expression files. It performs a molecular profile analysis, followed by a pathway analysis, augmented with interactions discovered by natural language processing from 20 million PubMed reports. The output of WGA consists of a list of drug candidates with rationales and scores along with literature evidence that supports their consideration. The results were compared to the human curated reports produced by the POG team. Results: In all 29 instances of retrospective analysis, WGA finds actionable insights and identifies potential drugs for consideration. The automated generation of these insights is achieved by WGA in minutes. Conclusions: With increasing adoption of molecularly targeted therapies, there is a strong need to continuously update the relationships between genomic alterations, cancer biology and the drugs that target these potential drivers. This is a tedious task that required extensive and time consuming review of latest scientific literature. The WGA may allow for more efficient and robust way of performing the analysis. Clinical trial information: NCT01802905.
Erythrocytes Are Oxygen-Sensing Regulators of the Cerebral Microcirculation
Authors: Helen Shinru Wei, Hongyi Kang, Izad-Yar Daniel Rasheed, Sitong Zhou, Nanhong Lou, Anna Gershteyn, Evan Daniel McConnell, Yixuan Wang, Kristopher Emil Richardson, Andre Francis Palmer, Chris Xu, Jiandi Wan, Maiken Nedergaard
Journal: Neuron (2016)
Treatment (trx) of metastatic renal cell carcinoma (mRCC) with angiogenesis inhibitors (AIs): Safety and treatment patterns observed in Taiwanese patients.
Authors: Y. Chang, Y. Ou, C. Huang, P. Chiang, C. Chuang, S. Kina, F. Vekeman, R. Goglia, M. Neary, M. S. Duh
Journal: Journal of Clinical Oncology (2011)

e15146 Background: AIs have demonstrated efficacy in patients with mRCC. This study analyzed the safety and trx patterns of AIs in real-world clinical practice in Taiwan. Methods: Medical records from 5 medical centers in Taiwan were retrospectively reviewed. Study subjects were adults with mRCC who received sunitinib [SU] (N=67), sorafenib (N=13), bevacizumab (N=4), or temsirolimus (N=4) as 1st-line AIs from 1/1/2005 to 11/15/2010. Proportions of patients with trx modification, i.e. discontinuation, interruption, or dose change, and reasons for trx modifications were determined. Time to trx discontinuation and adverse events (AEs) were assessed during trx with 1st-line angiogenesis inhibitor. Results: Due to the small sample sizes in the other trx groups, only results for SU are summarized. Only 24% of SU patients initiated trx with the recommended dosing of 50 mg QD 4/2. All grade and grade 3/4 AEs were observed in 85.1% and 23.9% of patients, respectively. The most common all grade AEs observed were hand-foot syndrome (38.8%), diarrhea (22.4%), anorexia (22.4%), and mucositis or stomatitis (20.9%). 46.3% of patients had at least one trx modification due to AEs (discontinuations: 17.9%, interruptions: 17.9%, and dose reductions: 25.4%). Among patients who discontinued trx, 67.8% did so within the first 18 weeks of trx; mean 1st-line trx duration was 6.8 months. Conclusions: This analysis of real-world clinical utilization of sunitinib to treat mRCC revealed unique dosing patterns in Taiwan. It also showed that AEs are common and result in numerous trx modifications. This suggests a continuing need for effective and more tolerable trx for mRCC. Validation of these data in a larger sample is warranted. Trx patterns, n (%) SU N=132 Pts with SU trx discontinuation 28 (41.8%) Due to progressive disease 9 (13.4%) Due to AEs 12 (17.9%) Pts with SU trx interruption 16 (23.9%) Due to AEs 12 (17.9%) Pts with SU dose reduction 24 (35.8%) Due to AEs 17 (25.4%) Pts with SU dose increase 10 (14.9%) Due to progressive or advanced disease 1 (1.5%) Pts with ≥1 SU trx modifications due to AEs 31 (46.3%)
Abstract 3977: Evaluation of miR10b and miR9 expression in breast cancer and correlations with distant metastases development
Authors: Raffaela Barbano, Barbara Pasculli, Massimiliano Copetti, Andrea Fontana, Michelina Coco, Lorenzo Vitulano, Maria Luana Poeta, Francesca Picardo, Gianfranco Marangi, Roberto Murgo, Luigi Ciuffreda, Vanna Maria Valori, Vanna Maria Valori, Maria Morritti, Evaristo Maiello, Vito Michele Fazio, Paola Parrella
Journal: Cancer Research (2015)

Abstract We have recently demonstrated that the evaluation of miR10b expression relative to its normal counterparts (Relative Expression Ratio, RER) is able to predict patients risk to develop distant metastases. To confirm these results and evaluate whether other microRNAs could be predictive of outcome in breast cancer we evaluated the expression of miR10b and miR9 in paired tumors and apparently normal breast tissues 2 cm distant from tumour (NBT) on an extended cohort (n = 127) with a longer follow up (median 42 months). As control normal breast tissues from 10 healthy subjects (HBT) treated by reductive mammoplasty were analyzed. An increased expression was seen for the miR9 and miR10b in NBT samples as compared with HBT (P&amp;lt;0.01). Whereas the expression of each of the two miRNAs was significantly lower in tumour samples as compared to the NBT specimens with RER value of 0.15 for miR10b (P = 0.001) and 0.59 for miR9 (P = 0.05). However only higher miR10b RERs were associated with distant metastases development in multivariable analysis (HR = 1.12; P = 0.04). Our results confirm the role of miR10b as predictive biomarkers of metastases development in breast cancer. In addition our data suggest a deregulation of miRNAs expression in the normal tissue surrounding tumor as compared to normal breast of healthy individuals. Citation Format: Raffaela Barbano, Barbara Pasculli, Massimiliano Copetti, Andrea Fontana, Michelina Coco, Lorenzo Vitulano, Maria Luana Poeta, Francesca Picardo, Gianfranco Marangi, Roberto Murgo, Luigi Ciuffreda, Vanna Maria Valori, Vanna Maria Valori, Maria Morritti, Evaristo Maiello, Vito Michele Fazio, Paola Parrella. Evaluation of miR10b and miR9 expression in breast cancer and correlations with distant metastases development. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3977. doi:10.1158/1538-7445.AM2015-3977
Cobimetinib combined with vemurafenib in advanced BRAFV600-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial
Authors: Paolo A Ascierto, Grant A McArthur, Brigitte Dréno, Victoria Atkinson, Gabrielle Liszkay, Anna Maria Di Giacomo, Mario Mandalà, Lev Demidov, Daniil Stroyakovskiy, Luc Thomas, Luis de la Cruz-Merino, Caroline Dutriaux, Claus Garbe, Yibing Yan, Matthew Wongchenko, Ilsung Chang, Jessie J Hsu, Daniel O Koralek, Isabelle Rooney, Antoni Ribas, James Larkin
Journal: The Lancet Oncology (2016)
A novel High dose chemotherapy strategy with Bendamustine in Adjunct to Etoposide, Aracytin and Melphalan (BeEAM) Followed by Autologous Stem cell rescue in Resistant/Relapsed Hodgkin and Non-Hodgkin Lymphoma Patients: a Phase I Study.
Authors: Giuseppe Visani, Lara Malerba, Piero Galieni, Claudio Giardini, Sadia Falcioni, Marco Rocchi, Alessandro Isidori
Journal: Blood (2009)
Abstract 146: Genomic analysis of endometrial stromal sarcoma of uterus
Authors: Youn Jin Choi, Soo Young Hur, Jong Sup Park, Keun Ho Lee, Yoon Kyung Lee
Journal: Cancer Research (2016)

Abstract Although recurrent gene fusions such as JAZF1-JJAZ1 are considered driver events for endometrial stromal sarcoma (ESS) development, other genomic alterations remain largely unknown. In this study, we performed whole-exome sequencing, transcriptome sequencing and copy number profiling for five ESSs (three low-grade ESS (LG-ESS) and two undifferentiated uterine sarcomas (UUSs)). All three LG-ESSs exhibited either one of JAZF1-SUZ12, JAZF1-PHF1 and MEAF6-PHF1 fusions, whereas the two UUSs did not. All ESSs except one LG-ESS exhibited copy number alterations (CNAs), many of which encompassed cancer-related genes. In UUSs, five CNAs encompassing cancer-related genes (EZR, CDH1, RB1, TP53 and PRKAR1A) accompanied their expressional changes, suggesting that they might stimulate UUS development. We found 81 non-silent mutations (35 from LG-ESSs and 46 from UUSs) that included 15 putative cancer genes catalogued in cancer-related databases, including PPARG and IRF4 mutations. However, they were non-recurrent and did not include any well-known mutations, indicating that point mutations may not be a major driver for ESS development. Our data show that gene fusions and CNAs are the principal drivers for LG-ESS and USS, respectively, but both may require additional genomic alterations including point mutations. These differences may explain the different biologic behaviors between LG-ESS and UUS. Our findings suggest that ESS development requires point mutations and CNAs as well as the gene fusions. Clinical and histologic characteristics of five endometrial stromal sarcomasAgeHistopathology gradeDiagnosisSpecimen statusTNMCase 132Low-gradeLG-ESSPrimaryT1bN0M0Case 234Low-gradeLG-ESSPrimaryT1bN1M0Case 357Low-gradeLG-ESSPrimaryTxNxM1Case 465High-gradeUUSMetastaticT2aN0M0Case 557High-gradeUUSMetastaticTxNxM1 Citation Format: Youn Jin Choi, Soo Young Hur, Jong Sup Park, Keun Ho Lee, Yoon Kyung Lee. Genomic analysis of endometrial stromal sarcoma of uterus. [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 146.
Scrutinizing Alternative Paths to Medicaid Expansion
Authors: Frank J. Thompson, Joel C. Cantor
Journal: JAMA Internal Medicine (2016)

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Data Selection and Treatment of Chemicals Tested for Genotoxicity and Carcinogenicity
Authors: Nicola Loprieno, Guido Boncristiani, Gregorio Loprieno, Marco Tesoro
Journal: Environmental Health Perspectives (1991)

A database containing qualitative and quantitative results of experimental studies in the fields of genotoxicity and carcinogenicity has been developed. By analyzing results of the studies performed by the U.S. National Toxicology Program, or by a similar program developed in Japan, or reported in the scientific literature, as well performed by private organizations, information has been collected relating to 3389 chemicals, identified by their CAS number. The studies considered for the database include three genotoxicity/mutagenicity short-term test (STTs), namely, two in vitro (Salmonella, gene mutation assay, and mammalian cells/human lymphocytes chromosome aberration assay) and one in vivo, the rodent bone marrow micronucleus assay. To investigate the possible predictive value of these STT assays for carcinogenicity, the results of animal long-term bioassays have also been collected. We have re-evaluated all the genotoxicity studies and the majority of those cases studied in different laboratories with contrasting results has been resolved; a small proportion of questionable cases is, however, still present in the database. In total, 2898 (85.5%) of the chemicals have been tested in the Salmonella assay; 1399 (41.3%) have been tested in the in vitro chromosome aberration assay; 319 (9.4%) have been tested in the in vivo rodent bone marrow cell micronucleus assay; 716 (21.2%) of the chemicals have been tested in the in vivo animal long-term bioassay. For 1118 chemicals tested in the Salmonella assay, 30,650 quantitative studies have been included in the database, thus allowing a possible classification of mutagenic chemicals according to their mutagenic potency.(ABSTRACT TRUNCATED AT 250 WORDS)