tbuckley/cabot-search huggingface dataset:
Asymptomatic COPD, until you take it to exertion
Authors: Lowie E G W Vanfleteren
Journal: Thorax (2016)

COPD is a growing problem worldwide, with a staggering high number of affected subjects1 and a huge burden for society in terms of days of work lost and healthcare costs.2 COPD is closely related to smoking, and continued smoking in patients with COPD is associated with further deterioration in lung function.3 Despite elaborate societal preventive measures and smoking discouragement campaigns, smoking prevalence is still high and adolescents and young adults still start smoking. Although WHO reports a declining smoking prevalence worldwide and in many countries, there were still over 1.1 billion people who smoked tobacco in 2015.4 A population-based cohort study (inclusion 2007–2009) in adults aged more than 40 years in the Netherlands, for example, showed that overall smoking prevalence was 23% and only 34% were never smokers.5 Population surveys from 2012 in the Netherlands in age 20+ showed a similar 23% of smokers and 18% of adolescents (10–19 years) reported to have smoked in the last 4 weeks.6 Hence, despite all the efforts, smoking is still universally present and COPD continues to rise in ‘cause of death’ tables. In 2012, it was ranked third after ischaemic heart disease and stroke.7

An early diagnosis of COPD is warranted for maximal intervention in an early phase, including improving health behaviour, physical activity, smoking cessation and potential pharmacological treatment. Unfortunately, the prevalence of underdiagnosis of COPD is universally high as shown by the international Burden of Obstructive Lung Disease (BOLD) study that systematically evaluated subjects older than 40 years in the general population using standardised spirometry.8 Case-finding …
Abstract 3301: Breast cancer subtypes have distinct microbial and immune cytolytic transcriptomic signatures
Authors: Chandra Sekhar Pedamallu, Matthew Meyerson, Akinyemi Ojesina
Journal: Cancer Research (2016)

Abstract Background: The role of genetic mutations in breast cancer is well documented and has formed the basis for novel therapies. However, the impact of viral and bacterial infection in the pathogenesis of breast cancer is not well understood. Methods: We analyzed RNA sequencing (RNASeq) data generated by the Cancer Genome Atlas (TCGA) from over 900 pairs of breast tumor and adjacent normal tissues, using our pathogen discovery tool, PathSeq. We developed a novel metric for quantifying and normalizing microbial sequence abundance from RNASeq data by correcting for both the sequencing coverage and relative genome sizes of bacteria in the dataset. We also performed linear discriminant analyses (LDA) to test the hypothesis that the differences between the canonical breast cancer subtypes can be modeled on microbial abundance data. In addition, we interrogated the human gene expression data derived from the RNASeq dataset to determine the relationships between the breast cancer subtypes and immune cytolytic activity (CYT index; defined as the geometric mean of the expression levels of perforin and granzyme). Results: Viral sequences were rare but we identified bacterial sequences to varying degrees of abundance. Intriguingly, we demonstrated that microbial abundance data can be used to recapitulate the well-established PAM50 gene expression-based subsets. Comparison of tumors and adjacent normal tissues also revealed subtype-associated microbial profiles. In addition, we observed that the basal and Her2 subtypes of breast cancer had a higher frequency of tumors with high CYT index compared with luminal A and B subtypes. Conclusion: This study has revealed that the various breast cancer subtypes have unique microbial transcriptomic signatures as well as differential immune cytolytic activity profiles. These data suggest the potential for differential responses of breast cancer subsets to immunotherapy. Citation Format: Chandra Sekhar Pedamallu, Matthew Meyerson, Akinyemi Ojesina. Breast cancer subtypes have distinct microbial and immune cytolytic transcriptomic signatures. [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 3301.
Abstract 4909: The oncolytic peptide LTX-315 enhances tumor-specific immune responses and tumor regression in murine 4T1 breast cancer when combined with doxorubicin
Authors: Meng Yu Wang, Alexander Kristian, Ketil Camilio, Baldur Sveinbjornsson, Gunhild Mari Mælandsmo, Gunnar Kvalheim, Øystein Rekdal
Journal: Cancer Research (2016)

Abstract The oncolytic effect of LTX-315 involves perturbation of the plasma membrane and distortion of the mitochondrial membrane with subsequent release of DAMPs (Damage-Associated Molecular Pattern molecules) such as ATP, cytochrome C and HMGB1 (1,2). Also multidomain proteins from the BCL-2 family seem to be partially involved in LTX-315 mediated killing (3). In addition, LTX-315 induces the hallmarks of immunogenic cell death (4). Preclinical studies have demonstrated that LTX-315 is able to induce complete tumour regression after intra-tumoral treatment (5,6). In this study the effect of combining intratumoral administration of LTX-315 and systemic treatment with Doxorubicin was investigated in the murine 4T1 breast cancer model. The combination treatment was investigated both in s.c. tumors and in tumors established in the mammary fat pad. The 4T1 cell were labeled with mcherry reporter gene in order to assess tumor growth by whole body imaging. LTX-315 (1 mg in 50 ìl) was injected intratumorally for three consecutive days. Doxorubicin (8mg/kg) was injected into the tail vein as a single dose together with the first injection of LTX-315. Tumor growth was assessed by caliper measurements and whole body luminescence. The combination of local administration of LTX-315 and systemic Doxorubicin, demonstrated significant synergy in both s.c. tumors and in tumors growing in the mammary fat pad. Furthermore, the combination induced a systemic tumour specific immune response since tumors did not develop in cured animals when re-challenged with tumor cells. The tolerable safety profile and novel mode of action of LTX-315 indicate a rationale for combining LTX-315 with other immunotherapies, targeted agents, and chemotherapy. References: 1) Forveille et al., Cell Cycle (2015) 2) Eike et al., Oncotarget (2015) 3) Zhou et al., Oncotarget (2015) 4) Zhou et al. Cell Death &amp; Differentiation (In rev) 5) Camilio et al., Cancer Immunol Immunother (2014) 6) Camilio et al., Oncoimmunology (2014) Citation Format: Meng Yu Wang, Alexander Kristian, Ketil Camilio, Baldur Sveinbjornsson, Gunhild Mari Mælandsmo, Gunnar Kvalheim, Øystein Rekdal. The oncolytic peptide LTX-315 enhances tumor-specific immune responses and tumor regression in murine 4T1 breast cancer when combined with doxorubicin. [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 4909.
ISLES 2015 - A public evaluation benchmark for ischemic stroke lesion segmentation from multispectral MRI
Authors: Oskar Maier, Bjoern H. Menze, Janina von der Gablentz, Levin Häni, Mattias P. Heinrich, Matthias Liebrand, Stefan Winzeck, Abdul Basit, Paul Bentley, Liang Chen, Daan Christiaens, Francis Dutil, Karl Egger, Chaolu Feng, Ben Glocker, Michael Götz, Tom Haeck, Hanna-Leena Halme, Mohammad Havaei, Khan M. Iftekharuddin, Pierre-Marc Jodoin, Konstantinos Kamnitsas, Elias Kellner, Antti Korvenoja, Hugo Larochelle, Christian Ledig, Jia-Hong Lee, Frederik Maes, Qaiser Mahmood, Klaus H. Maier-Hein, Richard McKinley, John Muschelli, Chris Pal, Linmin Pei, Janaki Raman Rangarajan, Syed M.S. Reza, David Robben, Daniel Rueckert, Eero Salli, Paul Suetens, Ching-Wei Wang, Matthias Wilms, Jan S. Kirschke, Ulrike M. Krämer, Thomas F. Münte, Peter Schramm, Roland Wiest, Heinz Handels, Mauricio Reyes
Journal: Medical Image Analysis (2016)
Abstract 1135: FYN expression potentiates FLT3-ITD-induced mitogenic signaling in acute myeloid leukemia
Authors: Rohit A. Chougule, Julhash U. Kazi, Lars Rönnstrand
Journal: Cancer Research (2016)

Abstract FYN is a non-receptor tyrosine kinase belonging to the SRC family of kinases. SRC family kinases are frequently over-expressed in human cancers, and play key roles in cancer cell invasion, metastasis, proliferation, survival and many other biological processes. SRC has long been recognized as an important oncogene; but little attention has been given to its other family members such as FYN. In this report, we have studied the role of FYN in FLT3 signaling with respect to acute myeloid leukemia (AML). FLT3 is a type III receptor tyrosine kinase which is found to be mutated in around 30% of AML cases. We observed that FYN displays a strong association with wild-type FLT3 as well as oncogenic FLT3-ITD. While association with wild-type FLT3 is dependent on ligand stimulation, it is constitutively associated with FLT3-ITD. In addition, a kinase-dead FLT3 mutant was unable to associate with FYN suggesting that FLT3 activation is required for association with FYN. A FYN SH2-domain mutant lacking a critical arginine residue was unable to associate with FLT3 indicating that FYN associates with FLT3 through its SH2 domain. A phopho-peptide fishing experiment identified multiple FYN binding sites in FLT3, which partially overlap with the known SRC binding sites but also differ from these sites. To understand the role of FYN in FLT3 signaling, we have generated Ba/F3-FLT3/FYN or Ba/F3-FLT3/empty vector cell lines. We observed that expression of FYN results in enhanced phosphorylation of AKT, ERK1/2 and p38 phosphorylation in response to ligand stimulation. Ba/F3-FLT3-ITD cells overexpressing FYN also showed higher STAT5 activation. Furthermore, FYN expression led to a significant increase in FLT3-ITD-dependent cell proliferation but did not alter apoptosis induced by cytokine starvation. Finally, we showed that FYN expression was deregulated in AML patient samples and that higher expression of FYN in combination with FLT3-ITD expression correlates with poor prognosis in AML. Taken together our data suggest that FYN cooperates with oncogenic FLT3-ITD which results in poor prognosis in AML and therefore inhibition of FYN in combination with FLT3 inhibition will most likely be beneficial for AML patients. Citation Format: Rohit A. Chougule, Julhash U. Kazi, Lars Rönnstrand. FYN expression potentiates FLT3-ITD-induced mitogenic signaling in acute myeloid leukemia. [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 1135.
P0933 : NGM282 exhibits potent anti-inflammatory and anti-fibrotic activity in FXR-null mice with non-alcoholic steatohepatitis (NASH) histopathology
Authors: L. Ling, M. Zhou, H. Yang, M. Humphrey, M. Learned, S. Rossi, A. DePaoli, H. Tian
Journal: Journal of Hepatology (2015)
Abstract 1121: Validation of FOXR2 and ARHGAP36 as oncogenes in medulloblastoma
Authors: Pauline Jackson, Alex Larsson, Paramita Das, David Largaespada
Journal: Cancer Research (2016)

Abstract We are working to validate two putative oncogenes in medulloblastoma (MB), ARHGAP36 and FOXR2. These genes were identified as MB drivers using a Sleeping Beauty mutagenesis screen in mice and are overexpressed in subsets of human MB. We are using gain (GOF) and loss of function (LOF) studies both in vitro and in vivo to understand the roles of FOXR2 and ARHGAP36 in MB genesis. In GOF studies, both genes individually drove anchorage independent growth in a mouse cerebellar progenitor cell line (C17.2) and a human MB cell line (ONS76). When overexpressed individually in C17.2 cells, both FOXR2 and ARHGAP36 drove tumor formation in the flank of NU/J mice. We are also using an orthotopic injection model with C17.2 cells overexpressing either ARHGAP36 or FOXR2 individually to determine if these genes drive tumor formation in a more relevant setting. RNA sequencing and reverse-phase protein array analyses were also performed on WT and C17 cells overexpressing each oncogene to identify their effects in an unbiased manner. We are working to validate those effects using RT-PCR and Western analysis. In LOF studies, the CRISPR/Cas system is being used to create mutations in either the ARHGAP36 or FOXR2 locus in human MB cell lines (ONS76, MED8A, Daoy). This has been accomplished with ARHGAP36 in ONS76 cells, and we are currently characterizing those cells using proliferation, soft agar colony formation, and tumor formation assays. Lastly, we are working to create GOF and LOF mouse models of both FOXR2 and ARHGAP36 to characterize their oncogenic potential in vivo. We identified ARHGAP36 and FOXR2 as putative oncogenes in MB and our findings may elucidate novel targets for therapeutic efforts aimed at treating patients with MB. Citation Format: Pauline Jackson, Alex Larsson, Paramita Das, David Largaespada. Validation of FOXR2 and ARHGAP36 as oncogenes in medulloblastoma. [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 1121.
Abstract 988: A novel long non-coding RNA, TSA-LINC2, regulates cellular growth and is associated with poor prognosis in breast cancer
Authors: Martin Pichler, Stefanie Cerk, Verena Stiegelbauer, Daniela Schwarzenbacher, Hui Ling
Journal: Cancer Research (2016)

Abstract Background: Long non-coding RNAs (LINCs) are an emerging class of molecules in cancer diagnosis and prognosis. The number of LINCs exceeds the number of protein-coding genes and their role in breast cancer is largely unknown. Methods: In this study we used non-adherent growing tumor spheres (“mammospheres”) as a model system to identify tumor-sphere associated (TSA) gene expression patterns. We used microarrays to profile different breast cancer cell lines and selected the most up/down-regulated differentially expressed genes by RT-PCR. Clinical correlations including survival analysis of almost 900 breast cancer patients in two independent cohorts and experimental evaluation of the biological function were done. Results: Among several TSA-genes, one novel not previously reported LINC, (that we termed TSA-LINC2) was significantly up-regulated in mammospheres (up to 50 fold, p&amp;lt;0.05). In patient samples, TSA-LINC2 was significantly up-regulated in cancer tissue compared to normal breast tissue, and high expression was associated with poor survival in different molecular breast cancer subtypes (p&amp;lt;0.05). Knock-down experiments of TSA-LINC2 in a panel of breast cancer cell lines led to significantly altered cellular growth, anchorage-independent growth and mammosphere formation in triple negative (p&amp;lt;0.05). Molecular profiling with gene expression arrays shows that TSA-LINC2 regulates cell cycle-associated genes. Conclusion: This novel long non-coding RNAis involved in breast cancer progression and might be useful as a prognostic marker in breast cancer patients. Citation Format: Martin Pichler, Stefanie Cerk, Verena Stiegelbauer, Daniela Schwarzenbacher, Hui Ling. A novel long non-coding RNA, TSA-LINC2, regulates cellular growth and is associated with poor prognosis in breast 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 988.
Adding targeted inhibition of PI3K and MAPK signaling pathways to standard chemotherapy in experimental pancreatic cancer.
Authors: Niranjan Awasthi, Margaret A. Schwarz, Roderich Schwarz
Journal: Journal of Clinical Oncology (2016)

278 Background: Treatment of pancreatic ductal adenocarcinoma (PDAC) remains a formidable challenge as gemcitabine (Gem) plus nab-paclitaxel (NPT) represent the current standard for systemic therapy of advanced PDAC. More than 90% of PDAC tumors harbor an activating mutation in the KRAS oncogene. Currently no therapeutics exist that can effectively target this oncogene product, but alternative strategies focus on inhibition of downstream effectors of KRAS signaling pathways. The RAF-MEK-ERK (MAPK) and the AKT-PI3K signaling pathways are well-described mediators of KRAS induced transformation and tumorigenesis and can be explored as targets for combination therapy. Methods: We evaluated combination treatment benefits of NPT+Gem with the MEK inhibitor trametinib (Tra) and the AKT inhibitor MK-2206 (MK) in experimental xenografts to test their therapeutic potential against PDAC. Results: Median animal survival in human intraperitoneal PDAC xenografts in mice revealed that the median survival was 21 days in controls; this was significantly improved by the NPT+Gem combination (35 days, a 67% increase over controls, p = 0.0007). Median survival was further increased by addition of MK-2206 or trametinib to NPT+Gem chemotherapy group: NPT+Gem+MK (39 days, a 86% increase over controls, p = 0.0003), NPT+Gem+Tra (43 days, a 105% increase over controls, p = 0.0003) and NPT+Gem+MK+Tra (48 days, a 129% increase over controls, p = 0.002). In human subcutaneous PDAC xenografts, MK-2206 or trametinib were able to enhance NPT+Gem effects. Compared to controls (100±34.8), the percent net local tumor growth in different therapy groups was: NPT+Gem 21.8±5.9 (p = 0.003), NPT+Gem+MK 17.2±4.8 (p = 0.002), NPT+Gem+Tra 7.1±11.2 (p = 0.002) and NPT+Gem+MK+Tra 5.7±9.1 (p = 0.001). In vivo effects of Tra and MK correlated with reduced expression of phospho-ERK and phospho-AKT in Western blots of tumor samples. Conclusions: These findings suggest that the effects of NPT+Gem can be enhanced through combined inhibition of MAPK and PI3K signaling pathways, which clinically could yield in improved antitumor results.
Twelve-Month and Lifetime Prevalence of Mental Disorders in Cancer Patients
Authors: Susanne Kuhnt, Elmar Brähler, Hermann Faller, Martin Härter, Monika Keller, Holger Schulz, Karl Wegscheider, Joachim Weis, Anna Boehncke, Bianca Hund, Katrin Reuter, Matthias Richard, Susanne Sehner, Hans-Ulrich Wittchen, Uwe Koch, Anja Mehnert
Journal: Psychotherapy and Psychosomatics (2016)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Psychological problems are common in cancer patients. For the purpose of planning psycho-oncological interventions and services tailored to the specific needs of different cancer patient populations, it is necessary to know to what extent psychological problems meet the criteria of mental disorders. The purpose of this study was to estimate the 12-month and lifetime prevalence rates of mental disorders in cancer patients. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A representative sample of patients with different tumour entities and tumour stages (n = 2,141) in outpatient, inpatient and rehabilitation settings underwent the standardized computer-assisted Composite International Diagnostic Interview for mental disorders adapted for cancer patients (CIDI-O). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The overall 12-month prevalence for any mental disorder was 39.4% (95% CI: 37.3-41.5), that for anxiety disorders was 15.8% (95% CI: 14.4-17.4), 12.5% (95% CI: 11.3-14.0) for mood disorders, 9.5% (95% CI: 8.3-10.9) for somatoform disorders, 7.3% (95% CI: 6.2-8.5) for nicotine dependence, 3.7% (95% CI: 3.0-4.6) for disorders due to general medical condition, and 1.1% (95% CI: 0.7-1.6) for alcohol abuse or dependence. Lifetime prevalence for any mental disorder was 56.3% (95% CI 54.1-58.6), that for anxiety disorders was 24.1% (95% CI: 22.3-25.9), 20.5% (95% CI: 18.9-22.3) for mood disorders, 19.9% (95% CI: 18.3-21.7) for somatoform disorders, 18.2% (95% CI: 16.6-20.0) for nicotine dependence, 6.4% (95% CI: 5.4-7.6) for alcohol abuse or dependence, 4.6% (95% CI: 3.8-5.6) for disorders due to general medical condition, and 0.2% (95% CI: 0.1-0.6) for eating disorders. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Mental disorders are highly prevalent in cancer patients, indicating the need for provision of continuous psycho-oncological support from inpatient to outpatient care, leading to an appropriate allocation of direct personnel and other resources.
Rituximab + IEV/MINE Second Line Approach in Relapsed/Refractory Non Hodgkin Lymphoma (NHL): Efficacy and Safety
Authors: Velia Bongarzoni, Barbara Anaclerico, Paola Anticoli Borza, Michele Cedrone, Anna Chierichini, Susanna Fenu, Benedetto Ronci, Mariangela Vittori, Maria Cantonetti, Maria Concetta Petti, Luciana Annino
Journal: Blood (2008)
Abstract LB-285: Bioinformatic identification of prognostic signature defined by copy number alteration and expression of <i>CCNE1</i> in non-muscle invasive bladder cancer
Authors: In-Sun Chu, Sun-Hee Leem
Journal: Cancer Research (2016)

Abstract Because non-muscle-invasive bladder cancer (NMIBC) is clinically heterogeneous, predicting disease progression for patients with bladder cancer still remains a major clinical challenge, despite numerous investigations for NMIBC. In this study we identify a prognostic signature to predict the heterogeneity of NMIBC using an integrative analysis of copy number and gene expression data. We analyzed the copy number and gene expression profile data of bladder cancer obtained from The Cancer Genome Atlas (TCGA) consortium. A prognostic signature based on copy number altered gene was developed and validated in three independent patient cohorts (n = 501). Diverse statistical methods were applied to identify and validate a signature. Of the fourteen significant copy number altered molecules reported previously, ten were significantly correlated between copy number and expression changes in the TCGA dataset. Among them, CCNE1 and its co-expressed genes were significantly associated with disease progression, which was validated in the independent cohorts. The CCNE1 signature was shown to be an independent risk factor by a multivariate analysis (HR 4.99, 95% CI = 1.054 to 23.659, P = 0.043). Lastly, gene network and upstream regulator analyses revealed that NMIBC progression might be mediated by CCND1-CCNE1-SP1 pathways. The prognostic molecular signature defined by copy number and expression changes of CCNE1 suggests a novel diagnostic tool for predicting the likelihood of progression in NMIBC. Citation Format: In-Sun Chu, Sun-Hee Leem. Bioinformatic identification of prognostic signature defined by copy number alteration and expression of CCNE1 in non-muscle invasive bladder 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 LB-285.