tbuckley/cabot-search huggingface dataset:
A Phylogenomic Framework to Study the Diversity and Evolution of Stramenopiles (=Heterokonts)
Authors: Romain Derelle, Purificación López-García, Hélène Timpano, David Moreira
Journal: Molecular Biology and Evolution (2016)

Stramenopiles or heterokonts constitute one of the most speciose and diverse clades of protists. It includes ecologically important algae (such as diatoms or large multicellular brown seaweeds), as well as heterotrophic (e.g., bicosoecids, MAST groups) and parasitic (e.g., Blastocystis, oomycetes) species. Despite their evolutionary and ecological relevance, deep phylogenetic relationships among stramenopile groups, inferred mostly from small-subunit rDNA phylogenies, remain unresolved, especially for the heterotrophic taxa. Taking advantage of recently released stramenopile transcriptome and genome sequences, as well as data from the genomic assembly of the MAST-3 species Incisomonas marina generated in our laboratory, we have carried out the first extensive phylogenomic analysis of stramenopiles, including representatives of most major lineages. Our analyses, based on a large data set of 339 widely distributed proteins, strongly support a root of stramenopiles lying between two clades, Bigyra and Gyrista (Pseudofungi plus Ochrophyta). Additionally, our analyses challenge the Phaeista-Khakista dichotomy of photosynthetic stramenopiles (ochrophytes) as two groups previously considered to be part of the Phaeista (Pelagophyceae and Dictyochophyceae), branch with strong support with the Khakista (Bolidophyceae and Diatomeae). We propose a new classification of ochrophytes within the two groups Chrysista and Diatomista to reflect the new phylogenomic results. Our stramenopile phylogeny provides a robust phylogenetic framework to investigate the evolution and diversification of this group of ecologically relevant protists.
Abstract 1789: Estrogen receptor alpha and beta gene expression in benign breast tissue of high risk premenopausal women treated with the SERM acolbifene
Authors: Bruce F. Kimler, Teresa A. Phillips, Carol J. Fabian
Journal: Cancer Research (2016)

Abstract Background We conducted a pilot study to assess the feasibility of a 4th generation selective estrogen receptor modulator (SERM) acolbifene as a breast cancer prevention agent in premenopausal women at high risk for development of breast cancer [Cancer Prev Res 8, December 2015]. Favorable modulation of biomarkers was observed in benign breast tissue acquired before and after intervention. This included reduction in proliferation (Ki-67 immunocytochemistry) and decreases in expression of genes that code for ERα, pS2, and PgR. While ERα is over-expressed and stimulatory in breast carcinogenesis, ERβ which would be inhibitory is down-regulated. Thus, a change in the ratio of gene expression might be most informative. We have now analyzed gene expression of ERβ so as to examine whether it, or the ratio of ERα to ERβ, may contribute to assessment of response. Methods Premenopausal women at elevated risk for breast cancer were screened by random periareolar fine needle aspiration (RPFNA) performed during the follicular phase of the menstrual cycle. Eligible women (n = 25) received 6-8 months of open-label acolbifene (20 mg/d), followed by repeat RPFNA. Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was performed on 16 paired specimens for several genes associated with estrogen activity: estrogen receptor 1 (ESR1) for ERα, trefoil factor 1 (TFF1) for pS2, GREB1 for growth regulation by estrogen in breast cancer 1, PGR for progesterone receptor, and estrogen receptor 2 (ESR2) for ERβ. The quantity of each biomarker transcript was expressed relative to the reference transcript HPRT1. Further normalization by epithelial cell markers (KRT19 for cytokeratin 19 or CDH1 for E-Cadherin) did not materially alter the results. Results Significant changes had been previously shown for transcripts that code for pS2 (15 decreases, 1 increases; p = 0.002), ERα (11↓, 5↑; p = 0.013), and PgR (15↓, 1↑; p = 0.001); plus a suggestion of effect of GREB-1α (10↓, 6↑; p = 0.074). ERβ exhibited a general increase, but this was not statistically significant (5↓, 11↑; p = 0.24). However, the reduction of the ratio of ERα to ERβ was statistically significant (15↓, 1↑; p = 0.002). Conclusions Assessment of the ratio of gene expression for ERα to ERβ, and possibly their protein products by immunocytochemistry, may provide a useful surrogate endpoint biomarker by which to monitor response to SERMs used for breast cancer chemoprevention in premenopausal women. Supported by NO1-CN-35135. Citation Format: Bruce F. Kimler, Teresa A. Phillips, Carol J. Fabian. Estrogen receptor alpha and beta gene expression in benign breast tissue of high risk premenopausal women treated with the SERM acolbifene. [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 1789.
Abstract 5092: CD151-α3β1 integrin complexes are prognostic markers of glioblastoma and cooperate with EGFR to drive tumor cell motility and invasion
Authors: Pengcheng Zhou, Sonia Erfani, Rosalind Segal, Craig Horbinski, Xiuwei H. Yang
Journal: Cancer Research (2016)

Abstract Glioblastoma, one of the most aggressive forms of brain cancer, is featured by high tumor cell motility and invasiveness, which not only fuel tumor infiltration, but also enable escape from surgical or other clinical interventions. Thus, better understanding of how these malignant traits are controlled will be key to the discovery of novel biomarkers and therapies against this deadly disease. Tetraspanin CD151 and its associated α3β1 integrin have been implicated in facilitating tumor progression across multiple cancer types. How these adhesion molecules are involved in the progression of glioblastoma, however, remains largely unclear. Here, we examined an in-house tissue microarray-based cohort of 96 patient biopsies and TCGA dataset to evaluate the clinical significance of CD151 and α3β1 integrin. Functional, biochemical and signaling analyses were also conducted to understand how these molecules promote the aggressiveness of glioblastoma at molecular and cellular levels. Results from our analyses showed that CD151 and α3 integrin were significantly elevated in glioblastomas at both protein and mRNA levels, and exhibited strong inverse correlation with patient survival (p &amp;lt;0.006). These adhesion molecules also formed tight protein complexes and synergized with EGF/EGFR to accelerate tumor cell motility and invasion. Furthermore, disruption of such complexes enhanced the survival of tumor-bearing mice in a xenograft model, and impaired activation of FAK and small GTPases. Also, knockdown- or pharmacological agent-based attenuation of EGFR, FAK or Graf (ARHGAP26)/small GTPase-mediated pathways markedly mitigated the aggressiveness of glioblastoma cells. Collectively, our findings provide clinical, molecular and cellular evidence of CD151-α3β1 integrin complexes as promising prognostic biomarkers and therapeutic targets for glioblastoma. Citation Format: Pengcheng Zhou, Sonia Erfani, Rosalind Segal, Craig Horbinski, Xiuwei H. Yang. CD151-α3β1 integrin complexes are prognostic markers of glioblastoma and cooperate with EGFR to drive tumor cell motility and invasion. [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 5092.
Effect of liner and porcelain application on zirconia surface structure and composition
Authors: Tariq F Alghazzawi, Gregg M Janowski
Journal: International Journal of Oral Science (2016)

The purpose of this study was to determine if there is an effect of liner and porcelain application (layering and pressing techniques) on the surface of yttria-stabilized tetragonal zirconia polycrystals (Y-TZP), which were exposed to permutations of liner, layered porcelain, and pressed porcelain. Scanning electron microscope (SEM)/energy dispersive spectroscope (EDS) was used to identify changes in composition and microstructure after removing liner and porcelain with hydrofluoric acid. Simulated aging was also conducted to determine the effect of liner and porcelain on low-temperature degradation. The control group had a typical equiaxed grain structure, referred to as unaffected. When covered with liner or porcelain, some areas changed in structure and composition and were termed affected. The frequency of affected structure decreased when liner was covered with either layered porcelain or pressed porcelain. There were statistical differences (P<0.05) in the composition between affected and unaffected for zirconium (layered porcelain with liner: affected=60% (0.8%) (m/m), unaffected=69% (4%), layered porcelain without liner: affected=59% (3%), unaffected=65% (3%)) and oxygen (layered porcelain with liner: affected=35% (2%), unaffected=26% (4%), layered porcelain without liner: affected=35% (3%), unaffected=30% (2%)). However, there were statistical differences (P<0.05) in the composition for zirconium and oxygen of the aged layered porcelain without liner only. The liner should not be used before porcelain application, especially when using the layering technique for zirconia restorations. Furthermore, pressing should be considered the technique of choice over layering.
Observational registry of sorafenib use in clinical practice across Child-Pugh subgroups: The GIDEON study
Authors: Jorge A. Marrero, Masatoshi Kudo, Alan P. Venook, Sheng-Long Ye, Jean-Pierre Bronowicki, Xiao-Ping Chen, Lucy Dagher, Junji Furuse, Jean-Francois H. Geschwind, Laura Ladrón de Guevara, Christos Papandreou, Tadatoshi Takayama, Arun J. Sanyal, Seung Kew Yoon, Keiko Nakajima, Robert Lehr, Stephanie Heldner, Riccardo Lencioni
Journal: Journal of Hepatology (2016)
Abstract 58: Metformin impacts IGF-1R/ Akt signaling and energy metabolism in lung adenocarcinoma
Authors: Gabriela C. Lobato, Steve Li, Imad Tarhoni, Wen-Rong Lie, Jeffrey A. Borgia
Journal: Cancer Research (2016)

Abstract Introduction: Clinical outcomes for type II diabetes patients diagnosed with NSCLC are superior for those receiving metformin relative to other diabetic medications, though the mechanism for this effect remains incompletely elucidated. We hypothesized that metformin induces changes in Akt-based signaling via AMPK that increases glycolytic flux, and adversely affects survival in cell-line models of lung adenocarcinoma. The objective for these studies is to investigate therapeutic strategies involving metformin that have the potential to synergize with strategies targeting IGF-1R/Akt signaling. Methods: The lung adenocarcinoma cell lines, A549 and H358, were treated with 0, 1, 5, 10 mM metformin for 24, 48, and 72 hours and evaluated for changes in expression and activity of IGF-1R/Akt signaling, as well as the expression of 17 enzymes involved in glycolytic and oxidative energy metabolism, all using Luminex® immunobead assays. In parallel, MTT assays were performed for up to 5 days to document changes in cellular proliferation/ death rates. Extracellular acidification was also monitored as a measure of glycolytic flux. All findings were collated and statistically evaluated using SPSS v19 (Chicago, IL) using independent t-tests or one-way ANOVA. Results: We observed that metformin decreased IGF-1R/Akt signaling while increasing the expression of the protein levels of the signaling intermediates. Treatment with metformin increased the expression of Akt, IRS-1, PTEN, GSK3alpha and TSC2 (p&amp;lt;0.05 for all). Further, metformin treatment decreased the mean ratio of phospho-/total pyruvate dehydrogenase and increased the expression of ATP Synthase (both p&amp;lt;0.05), and were associated (p&amp;lt;0.05) with a dose-dependent increase in extracellular acidification. Lower doses (0.1 mM) of metformin did not have a significant impact on cell proliferation at 5 days, but a dose-dependent decrease in cell numbers was observed, with 37% and 29% reduction in cell numbers documented (p&amp;lt;0.05) at 5 mM for the H358 and A549 cells, respectively. Conclusion: This study links changes with Akt signaling with changes in glycolytic flux and oxidative metabolism. This study suggests metformin may make an attractive adjunct for advanced NSCLC patients receiving therapy that mechanistically involves targeting Akt signaling and metabolic control, such as IGF1R inhibition. Citation Format: Gabriela C. Lobato, Steve Li, Imad Tarhoni, Wen-Rong Lie, Jeffrey A. Borgia. Metformin impacts IGF-1R/ Akt signaling and energy metabolism in lung adenocarcinoma. [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 58.
Restrictive IL-10 induction by an innocuous parainfluenza virus vector ameliorates nasal allergy
Authors: Keiichi Yamanaka, Takehisa Nakanishi, Kana Isono, Chisami Hasegawa, Hiroyasu Inada, Kento Mizutani, Yoshiaki Matsushima, Karin Okada, Tomotaka Mabuchi, Makoto Kondo, Akisa Yamagiwa, Masato Kakeda, Koji Habe, Tetsuya Nosaka, Esteban C. Gabazza, Hidetoshi Yamazaki, Hitoshi Mizutani, Mitsuo Kawano
Journal: Journal of Allergy and Clinical Immunology (2016)
Cardiac dysfunction in Pkd1-deficient mice with phenotype rescue by galectin-3 knockout
Authors: Bruno E. Balbo, Andressa G. Amaral, Jonathan M. Fonseca, Isac de Castro, Vera M. Salemi, Leandro E. Souza, Fernando dos Santos, Maria C. Irigoyen, Feng Qian, Roger Chammas, Luiz F. Onuchic
Journal: Kidney International (2016)
Abstract 4039: Mimotope variance analysis: A novel immunoprofiling method to monitor progression of cervical cancer
Authors: Espen Enerly, Mari Nygård, Madleen Orumaa, Arno Pihlak, Susan Pihelgas, Hilde Langseth, Toomas Neuman, Kaia Palm
Journal: Cancer Research (2016)

Abstract The purpose of the study was to identify and describe cervical cancer specific changes in humoral immune response by using a novel technology platform Mimotope Variation Analysis (MVA) developed by Protobios. The Janus Serum Bank is one of the world's oldest and largest population-based research biobanks established in 1973. The cohort is annually linked to the Cancer Registry of Norway using personal identification numbers. More than 1000 women have developed cervical cancer after donating sera. We identified sets of successive sera samples from ten patients with invasive cervical cancer, ten patients with pre-invasive cervical neoplasia and twenty cancer-free individuals (matched for age, gender, length of sample storage +3 months). For each subject we identified 4-10 samples donated to Janus over a period of up to 18 years, in total 213 samples. We applied MVA which combines phage display technology and high-throughput sequencing analysis to generate quantitative serologic profiles of millions of 12-mer peptide antigens called mimotopes from 2 μl of blood serum per analysis. Hierarchical clustering analysis of the top 5000 mimotopes from each sample resulted in individual-specific immunoprofiles. Multiple samples from the same person clustered together. Moreover, clustering reflected the time the sera was drawn suggesting that part of the individual immunoprofile is stabile over time. In conclusion, preliminary results suggests that Mimotope Variance Analysis generates individual-specific immunological profiles. This profile most likely reflect prior exposure environmental pathogens. Further, we aim to decode the differences in the immunological profiles between cancer patients and cancer-free subjects. Citation Format: Espen Enerly, Mari Nygård, Madleen Orumaa, Arno Pihlak, Susan Pihelgas, Hilde Langseth, Toomas Neuman, Kaia Palm. Mimotope variance analysis: A novel immunoprofiling method to monitor progression of cervical 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 4039.
C-type natriuretic peptide and natriuretic peptide receptor B signalling inhibits cardiac sympathetic neurotransmission and autonomic function
Authors: Jens Buttgereit, Julia Shanks, Dan Li, Guoliang Hao, Arvinder Athwal, Thomas H. Langenickel, Hannah Wright, Andrey C. da Costa Goncalves, Jan Monti, Ralph Plehm, Elena Popova, Fatimunnisa Qadri, Irina Lapidus, Brent Ryan, Cemil Özcelik, David J. Paterson, Michael Bader, Neil Herring
Journal: Cardiovascular Research (2016)

AimsB-type natriuretic peptide (BNP)-natriuretic peptide receptor A (NPR-A) receptor signalling inhibits cardiac sympathetic neurotransmission, although C-type natriuretic peptide (CNP) is the predominant neuropeptide of the nervous system with expression in the heart and vasculature.We hypothesized that CNP acts similarly to BNP, and that transgenic rats (TGRs) with neuron-specific overexpression of a dominant negative NPR-B receptor would develop heightened sympathetic drive.........
Risks of Myocardial Infarction, Death, and Diabetes in Identical Twin Pairs With Different Body Mass Indexes
Authors: Peter Nordström, Nancy L. Pedersen, Yngve Gustafson, Karl Michaëlsson, Anna Nordström
Journal: JAMA Internal Medicine (2016)

<h3>Importance</h3> Observational studies have shown that obesity is a major risk factor for cardiovascular disease and death. The extent of genetic confounding in these associations is unclear. <h3>Objective</h3> To compare the risk of myocardial infarction (MI), type 2 diabetes, and death in monozygotic (MZ) twin pairs discordant for body mass index (BMI). <h3>Design, Setting, and Participants</h3> A cohort of 4046 MZ twin pairs with discordant BMIs (difference &gt;0.01) was identified using the nationwide Swedish twin registry. The study was conducted from March 17, 1998, to January 16, 2003, with follow-up regarding incident outcomes until December 31, 2013. <h3>Main Outcomes and Measures</h3> The combined primary end point of death or MI and the secondary end point of incident diabetes were evaluated in heavier compared with leaner twins in a co-twin control analysis using multivariable conditional logistic regression. <h3>Results</h3> Mean (SD) baseline age for both cohorts was 57.6 (9.5) years (range, 41.9-91.8 years). During a mean follow-up period of 12.4 (2.5) years, 203 MIs (5.0%) and 550 deaths (13.6%) occurred among heavier twins (mean [SD] BMI, 25.9 [3.6] [calculated as weight in kilograms divided by height in meters squared]) compared with 209 MIs (5.2%) and 633 deaths (15.6%) among leaner twins (mean [SD] BMI, 23.9 [3.1]; combined multivariable adjusted odds ratio [OR], 0.75; 95% CI, 0.63-0.91). Even in twin pairs with BMI discordance of 7.0 or more (mean [SE], 9.3 [0.7]), where the heavier twin had a BMI of 30.0 or more (n = 65 pairs), the risk of MI or death was not greater in heavier twins (OR, 0.42; 95% CI, 0.15-1.18). In contrast, in the total cohort of twins, the risk of incident diabetes was greater in heavier twins (OR, 2.14; 95% CI, 1.61-2.84). Finally, increases in BMI since 30 years before baseline were not associated with the later risk of MI or death (OR, 0.97; 95% CI, 0.89-1.05) but were associated with the risk of incident diabetes (OR, 1.13; 95% CI, 1.01-1.26). <h3>Conclusions and Relevance</h3> In MZ twin pairs, higher BMI was not associated with an increased risk of MI or death but was associated with the onset of diabetes. These results may suggest that lifestyle interventions to reduce obesity are more effective in decreasing the risk of diabetes than the risk of cardiovascular disease or death.
Phase 2 trial of dovitinib in Bacillus Calmette-Guerin (BCG) refractory urothelial carcinoma (UC) with tumor FGFR3 mutations or over-expression: Hoosier Cancer Research Network GU12-157.
Authors: Noah M. Hahn, Trinity J. Bivalacqua, Ashley Ross, George J. Netto, Jong Chul Park, Timothy A. Masterson, Michael O. Koch, Richard Bihrle, Richard Foster, Thomas A. Gardner, Liang Cheng, David R Jones, Kyle McElyea, George Sandusky, Ziyue Liu, Scott A Turner, Gregory J. Tsongalis, Elizabeth R. Plimack, Richard E. Greenberg, Daniel M. Geynisman
Journal: Journal of Clinical Oncology (2016)

4526 Background: FGFR3 aberrations are common in low grade non-muscle invasive bladder cancer (NMIBC) tumors but decrease in frequency in metastatic UC. This multisite single-arm trial assessed the clinical and pharmacodynamic activity of dovitinib (an oral FGFR3/VEGFR2 inhibitor) in a treatment resistant, molecularly enriched NMIBC population. Methods: Patients (pts) with BCG refractory NMIBC despite at least 2 prior intravesical therapy regimens with increased tumor FGFR3 expression by centrally analyzed immunohistochemistry (IHC+) or FGFR3 mutations (Mut+) assessed in a CLIA-certified lab were eligible. Pts received dovitinib 500 mg once daily (5 days on / 2 days off) on q28d cycles. The primary endpoint was 6-month TURBT-confirmed complete response (CR) rate. Results: Between 11/2013 and 10/2014, 13 pts enrolled (10 IHC+ Mut-, 3 IHC+ Mut+). Demographics included: median age 70 years; 85% male; CIS (3 pts), Ta/T1 (8 pts), and Ta/T1 + CIS (2 pts); median prior regimens 3; median time from last treatment 6 months. Pts received a median of 4 dovitinib cycles. Dose reductions were required in 10 pts (77%). Treatment related grade 3/4 events included: fatigue, hypertension, hypertriglyceridemia (2 pts, 15% each); hepatotoxicity, stomatitis, rash (1 pt, 8% each). 6-month complete response rate was 8% (0% in IHC+ Mut-; 33% in IHC+ Mut+). The primary endpoint was not met. One pt remains a CR at 15+ months. One pt (8%) developed muscle-invasion on study. Pharmacodynamically active (94-5812 nM) dovitinib concentrations in urothelial tissue were observed in all 9 PK-evaluable pts. Reductions in pFGFR3 IHC staining were observed post-dovitinib treatment. A concordant urine FGFR3 mutation was noted in 1 of the 3 Mut+ pts. Conclusions: Oral dovitinib consistently achieved biologically active concentrations within the urothelium and demonstrated pharmacodynamic FGFR3 inhibition. Long-term administration of dovitinib was not feasible due to frequent treatment related toxicity. Absent clinical activity in FGFR3 IHC+ Mut- pts suggests that this should not be an entry criterion for future trials targeting FGFR3 in UC. Clinical trial information: NCT01732107.