tbuckley/cabot-search huggingface dataset:
Abstract P4-07-09: Differential expression of microRNAs (miRNAs) in HER2 negative breast cancer (BC)
Authors: T Pascual, A Gámez-Pozo, M Camara-Jurado, LM Manso, A Pérez-Campos, L Trilla, JA Fresno-Vara, EM Ciruelos
Journal: Cancer Research (2017)

Abstract Background: MiRNAs are non-coding single-stranded RNAs that control gene expression by directing their target mRNAs for degradation and/or posttranscriptional repression. Compared to mRNA signatures, miRNAs have better and stronger biomarker properties with 20 times more power in biomarker studies as compared to mRNAs (when comparing 20,000 mRNAs to ~ 1,000 miRNAs). Global downregulation of miRNAs has emerged as a common theme in human breast tumors and has been shown to contribute to oncogenesis Hormone receptor (HR) status is one of the most important factors influencing BC outcome. Several data indicate the extensive alterations in miRNAs regulation upon estrogen pathway and suggest the utility of considering miRNAs expression in the understanding the development of cancer disease, invasiveness, metastasis and treatment failure. Our aim was to identify differential expression miRNAs in HER2 negative BC. We previously reported a set of miRNAs deregulated in HR+/HER2- BC vs. Triple negative BC (TNBC). In this work we have validate these differences in a new cohort of BC patients. Methods: Total RNA was extracted samples extracted from primary breast cancer FFPE tissue. MicroRNAs expression was analyzed by RT-qPCR using TaqMan Arrays from Applied Biosystems. Normalization was performed using de DCt method with two housekeeping miRNAs identified previously identified using NorMean. MicroRNA expression values in each group were compared by the Mann Whitney test. Results: 121 patients with early HER2 negative BC were included in the present study. All patients showed absence of nodal involvement at the time of diagnosis. The median age at diagnosis was 56 years, 89 cases (74%) had positive estrogen receptor and 53 cases (44%) grade 3. miR-20a, miR-19a, miR-106a, miR-18a and miR-135b expression were significantly higher in TNBC samples, whereas miR-190b, miR-375, miR-449a, miR-342, miR-149, miR-193b, miR-214, miR-30a*and miR-30e* were significantly more expressed in ER+/HER2- samples. No significant differences were found in miR-139-5p expression between both groups. Conclusions: We have validated fourteen miRNAs that are differentially expressed between ER+/HER2- and TNBC breast cancer subtypes. Altered expression of miRNAs could be a potential therapeutic tool and promising biomarker in personalized treatment. Citation Format: Pascual T, Gámez-Pozo A, Camara-Jurado M, Manso LM, Pérez-Campos A, Trilla L, Fresno-Vara JA, Ciruelos EM. Differential expression of microRNAs (miRNAs) in HER2 negative breast cancer (BC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-07-09.
An Integrated Neuroscience Perspective on Formulation and Treatment Planning for Posttraumatic Stress Disorder
Authors: David A. Ross, Melissa R. Arbuckle, Michael J. Travis, Jennifer B. Dwyer, Gerrit I. van Schalkwyk, Kerry J. Ressler
Journal: JAMA Psychiatry (2017)

<h3>Importance</h3> Posttraumatic stress disorder (PTSD) is a common psychiatric illness, increasingly in the public spotlight in the United States due its prevalence in the soldiers returning from combat in Iraq and Afghanistan. This educational review presents a contemporary approach for how to incorporate a modern neuroscience perspective into an integrative case formulation. The article is organized around key neuroscience "themes" most relevant for PTSD. Within each theme, the article highlights how seemingly diverse biological, psychological, and social perspectives all intersect with our current understanding of neuroscience. <h3>Observations</h3> Any contemporary neuroscience formulation of PTSD should include an understanding of fear conditioning, dysregulated circuits, memory reconsolidation, epigenetics, and genetic factors. Fear conditioning and other elements of basic learning theory offer a framework for understanding how traumatic events can lead to a range of behaviors associated with PTSD. A circuit dysregulation framework focuses more broadly on aberrant network connectivity, including between the prefrontal cortex and limbic structures. In the process of memory reconsolidation, it is now clear that every time a memory is reactivated it becomes momentarily labile—with implications for the genesis, maintenance, and treatment of PTSD. Epigenetic changes secondary to various experiences, especially early in life, can have long-term effects, including on the regulation of the hypothalamic-pituitary-adrenal axis, thereby affecting an individual's ability to regulate the stress response. Genetic factors are surprisingly relevant: PTSD has been shown to be highly heritable despite being definitionally linked to specific experiences. The relevance of each of these themes to current clinical practice and its potential to transform future care are discussed. <h3>Conclusions and Relevance</h3> Together, these perspectives contribute to an integrative, neuroscience-informed approach to case formulation and treatment planning. This may help to bridge the gap between the traditionally distinct viewpoints of clinicians and researchers.
Impact of ASXL1 Mutations On Outcome After Reduced Intensity Allograft in Patients with Myelofibrosis
Authors: Nicolaus Kröger, Christian Koenecke, Haefaa Alchalby, Tatjana Zabelina, Robin Bollin, Marten Gehlhaar, Vera Dobbernack, Sofia Kade, Liu Huang, Arnold Ganser, Francis Ayuk, Christine Wolschke, Felicitas Thol, Michael Heuser
Journal: Blood (2012)
Correction: The Interaction of MUC1 and Myelin-Associated Glycoprotein
Journal: Cancer Research (2008)

In the article on the interaction of MUC1 and myelin-associated glycoprotein in the November 1, 2007 issue of Cancer Research (1), the footnote on page 10228 should read as follows:3J. Bara, personal communication, http://ifr31w3.toulouse.inserm.fr/mucines/Glycoconjugates.htm.
A randomized phase 2 study of a human antiplatelet-derived growth factor α (PDGFRα) monoclonal antibody (olaratumab, IMC-3G3) with paclitaxel/carboplatin or paclitaxel/carboplatin alone in previously untreated patients with advanced non-small cell lung cancer (NSCLC).
Authors: David E. Gerber, Toby Christopher Campbell, Paul Swanson, Ariel Lopez-Chavez, Lucas Wong, Afshin Dowlati, Amy Qin, Jan G. C. E. Cosaert, Maria Quintos Baggstrom
Journal: Journal of Clinical Oncology (2014)

8050 Background: In NSCLC, the PDGF-PDGFR axis mediates angiogenesis, local invasion, and tumor interstitial pressure. Olaratumab (IMC-3G3), a fully human monoclonal antibody, selectively binds human PDGFRα and blocks ligand binding. This open-label phase 2 study assessed the safety and efficacy of olaratumab added to paclitaxel/carboplatin (P/C) versus P/C alone in previously untreated patients (pts) with advanced NSCLC. Methods: Pts were randomized to receive up to 6 cycles of P 200 mg/m2and C AUC 6 (day 1) with (Arm A) or without (Arm B) olaratumab 15 mg/kg on days 1 and 8. The primary endpoint was progression-free survival (PFS), estimated by the Kaplan-Meier method. Olaratumab maintenance therapy was continued in Arm A until disease progression. At the time of progression, pts in Arm B could cross over to olaratumab monotherapy. Results: A total of 131 pts were randomized to Arm A (n=67) or Arm B (n=64). Demographics were similar between arms (57% male, 84% white, and median age 65 years). Most pts (74%) had nonsquamous NSCLC. Median PFS (Arm A: 19.1 weeks, Arm B: 19.0 weeks; p=0.21; hazard ratio [HR]: 1.29 [0.86–1.93]), median overall survival (OS) (Arm A: 51.3 weeks, Arm B: 50.1 weeks; p=0.87; HR: 1.04 [0.68–1.57]), and objective response rate (ORR) (Arm A: 42%, Arm B: 34%; p=0.47) were similar between arms. The 2 arms had similar toxicity profiles (Table). Adverse events leading to death occurred in 4 pts in Arm A (dyspnea, sepsis, disease progression, and myocardial infarction) and 2 pts in Arm B (respiratory failure and pneumonia). Conclusions: Adding olaratumab to P/C did not result in significant prolongation of PFS, OS, or ORR among previously untreated pts with advanced NSCLC. Clinical studies of olaratumab in other pt populations and biomarker analyses are underway. Clinical trial information: NCT00918203.Most frequent grade ≥3 treatment-emergent adverse events, % of patients. Arm A Arm B Neutropenia 30 19 Thrombocytopenia 13 5 Leukopenia 12 2 Fatigue 10 3 Dyspnea 8 6 Anemia 6 9 Hyperglycemia 6 3 Febrile neutropenia 6 2 Dehydration 6 2 Lymphopenia 6 2 Pulmonary embolism 3 8
Efficacy of Vindesine + Dexamethasone (VDS+Dexa.) in Elderly Patients with Relapsed or Refractory Malignant Lymphoma
Authors: Hiromi Yuasa, Hisashi Wakita, Yasuhiro Matsuura, Shunichirou Inagaki, Hironori Arai, Yoshikazu Utsu, Shinichi Masuda, Nobuyuki Aotsuka, Shosuke Sunami
Journal: Blood (2015)
Early Thymic Progenitor Leukemia (ETP-ALL) in Adults: A Distinct Molecular Entity,
Authors: Martin Neumann, Sandra Heesch, Claudia Seide, Ouidad Benlasfer, Thomas Burmeister, Stefan Schwartz, Nicola Gökbuget, Dieter Hoelzer, Wolf-Karsten Hofmann, Eckhard Thiel, Claudia D Baldus
Journal: Blood (2011)
Abstract A31: Biological effects of lutein and kale on the prevention of colonic inflammation and carcinogenesis
Authors: Chun Liu, Roderick T. Bronson, Xiang-Dong Wang
Journal: Cancer Research (2017)

Abstract Ulcerative colitis is a risk factor for colon cancer. Dietary lutein, a nutrient rich in kale, is inversely associated with the risk of developing colon cancer in human observational epidemiologic studies. Besides lutein, kale also contains abundant amounts of other bioactive components with anti-inflammatory, antioxidant, and anti-cancer properties. As a whole food approach, kale may provide more favorable biologic effects on colonic inflammation and neoplasia than lutein alone. Additionally, it is unclear if lutein prevents colon neoplasia via the inhibition of colonic inflammation. Using a dextran sulfate sodium (DSS)-induced colitis and neoplasia mouse model, we evaluated the effects of dietary lutein supplementation and kale on the DSS-induced colorectal inflammation, ulceration, hyperplasia, dysplasia and cancer. Two hundred sixty four 8-week old Swiss-Webster (CFW) mice were assigned to one of ten groups (n = 26 to 27 in each group [13 males and 13 to 14 females]) for 21 weeks as follows: 1) 0.0005% of lutein plus DSS; 2) 0.001% of lutein plus DSS; 3) 0.002% of lutein plus DSS; 4) 0.005% of lutein plus DSS; 5) kale equivalent to 0.0005% of lutein plus DSS; 6) kale equivalent to 0.001% of lutein plus DSS; 7) kale equivalent to 0.002% of lutein plus DSS; 8) kale equivalent to 0.005% of lutein plus DSS; 9) DSS only; and 10) control with no treatment. During the 21-week experimental period, mouse body weights were recorded weekly. At week 7, the mice in groups 1-9 were given DSS for 4 cycles (1 cycle = 1 week 3% of DSS in drinking water followed by 2-week water) to induce colitis and colorectal neoplasia. This report described the findings on the presence of clinical signs of colitis (hemoccult and loose stools, which were evaluated at the end of each week throughout the experiments), and the findings from histopathological evaluations (inflammation, ulceration, hyperplasia, dysplasia, and neoplasia). Dietary lutein and kale, particularly two higher doses (0.002% and 0.005%), reduced the DSS-induced hemoccult and loose stools, as well as the DSS-induced inflammation, ulceration, hyperplasia, dysplasia, and neoplasia. These data suggest that dietary lutein and kale may prevent the DSS-induced colorectal inflammation and associated preneoplastic and neoplastic lesions. Grant Funding Sources: This project was supported by Agriculture and Food Research Initiative Competitive Grant no. 2014-67017-21754 from the USDA National Institute of Food and Agriculture and by USDA/ARS grant 1950-51000-074S. Citation Format: Chun Liu, Roderick T. Bronson, Xiang-Dong Wang. Biological effects of lutein and kale on the prevention of colonic inflammation and carcinogenesis. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr A31.
Erratum: In vivo expression of an aberrant MYB-GATA1 fusion induces leukemia in the presence of GATA1 reduced levels
Authors: E Belloni, D Shing, C Tapinassi, A Viale, P Mancuso, O Malazzi, E Gerbino, V Dall'Olio, I Egurbide, M D Odero, F Bertolini, P G Pelicci
Journal: Leukemia (2011)
Abstract P6-01-04: Evolutionary analyses of matched primary and metastatic breast cancer reveal both linear and parallel progression with lack of axillary lymph node involvement
Authors: I Ullah, KG Muralidharan, A Alkodsi, U Kjällquist, G Stålhammar, J Lövrot, NF Martinez, J Lagergren, S Hautaniemi, J Hartman, J Bergh
Journal: Cancer Research (2017)

Abstract This abstract was withdrawn by the authors.
Final follow up survey of the randomized Pbo-controlled study of oregovomab (Ov) as a consolidation treatment for advanced ovarian cancer (OC): Insights into surveillance approaches
Authors: C. F. Nicodemus, J. S. Berek, B. C. Schultes, J. P. Balser, P. T. Taylor
Journal: Journal of Clinical Oncology (2006)

5079 Background: Ov is a monoclonal antibody specific for CA125 currently in two phase III studies as a consolidation immunotherapy for OC. A five year outcome follow up for patients participating in the prior randomized phase II study used to design the current pivotal trials has been completed. An assessment of survival post relapse (SPR) as a function of identifiable risk factors, and implications for long term survival survey methodology were reviewed. Methods: OC patients with no evaluable disease post front-line chemotherapy were randomized to IV infusions of OV or Pbo Q4 wks × 3, then Q12 wks. At relapse, therapy was stopped and second-line Rx was initiated without restriction. All patients were surveyed quarterly for long term outcomes for a pre-specified 5 years from initial randomization. A Kaplan-Meier (KM) analysis of overall survival and Cox multivariate analysis of SPR was completed. Results: 145 randomized participants were followed, including 67 designated as the successful front-line (SFLT) subpopulation identified to have characteristics favorable for intervention with immunotherapy (basis of ongoing phase III program). At five years, 47% of Ov (n = 73) and 37% of Pbo (n = 72) patients were alive overall, and 56% of Ov (n = 34) and 32% of Pbo (n = 33) were alive in the SFLT population. KM estimates of median survival are 57.5 mo [44.5-non-estimable (ne)] for Ov and 48.6 mo [30.9-ne] for Pbo in the overall population and ne mo [50.5-ne] for Ov and 48.6 mo [24-ne] for Pbo (p = 0.11) in the subpopulation. For relapsed patients, improved survival post relapse was most associated (Cox regression p &lt; 0.10) with lower CA125 velocity at relapse, treatment (Ov), and longer time to relapse. Conclusions: Survival data was consistent with previously reported time to relapse data in this study. For the SFLT, the 5 yr duration of survival survey and sample size were insufficient for a definitive outcome. However, results support the hypothesis that treatment with OvaRex may provide clinical benefit. The ongoing phase III studies will include a 10 year survival survey of 354 patients to definitively assess the impact of this treatment on long term survival. [Table: see text]
Xanthine Oxidase Mediates High Fat Diet-Induced Vascular Permeability via Junction Adhesion Molecule a Tyrosine Phosphorylation and Tight Junction Disruption
Authors: Rima Chattopadhyay, Venkatesh Kundamani-Sridharan, Alexander Tinnikov, Elena Dyukova, Nikhlesh K Singh, Sivareddy Kotla, Gadiparthi N Rao
Journal: Blood (2014)
Phase 1 Dose Escalation Study of TLK199 Tablets (Telintra), a Novel Glutathione Analog, in Myelodysplastic Syndrome.
Authors: Azra Raza, Magda Melcert, Naomi Galili, Scott E. Smith, John E. Godwin, Shelby Young, Lisa Meng, Marsha Jones, Gail L. Brown, Jeffery Lancet, Alan List
Journal: Blood (2007)
Cancer Risks in BRCA2 Mutation Carriers
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Carriers of germline mutations in the BRCA2 gene are known to be at high risk of breast and ovarian cancers, but the risks of other cancers in mutation carriers are uncertain. We investigated these risks in 173 breast-ovarian cancer families with BRCA2 mutations identified at 20 centers in Europe and North America. METHODS: Other cancer occurrence was determined in a final cohort of 3728 individuals, among whom 681 persons had breast or ovarian cancer and 3047 persons either were known mutation carriers, were first-degree relatives of known mutation carriers, or were first-degree relatives of breast or ovarian cancer patients. Incidence rates were compared with population-specific incidence rates, and relative risks (RRs) to carriers, together with 95% confidence intervals (CIs), were estimated by use of a maximum likelihood approach. Three hundred thirty-three other cancers occurred in this cohort. RESULTS: Statistically significant increases in risks were observed for prostate cancer (estimated RR = 4.65; 95% CI = 3.48-6.22), pancreatic cancer (RR = 3.51; 95% CI = 1.87-6.58), gallbladder and bile duct cancer (RR = 4.97; 95% CI = 1.50-16.52), stomach cancer (RR = 2.59; 95%CI = 1.46-4.61), and malignant melanoma (RR = 2.58; 95% CI = 1.28-5.17). The RR for prostate cancer for men below the age of 65 years was 7.33 (95% CI = 4.66-11.52). Among women who had already developed breast cancer, the cumulative risks of a second, contralateral breast cancer and of ovarian cancer by the age of 70 years were estimated to be 52.3% (95% CI = 41.7%-61.0%) and 15.9% (95% CI = 8.8%-22.5%), respectively. CONCLUSIONS: In addition to the large risks of breast and ovarian cancers, BRCA2 mutations may be associated with increased risks of several other cancers.
Abstract P6-03-02: Chronic CXCL12 exposure induces a metastatic phenotype in ER-positive breast cancer cells through transcriptional reprogramming
Authors: J Sun, JM Slingerland, ME Lippman
Journal: Cancer Research (2017)

Abstract The chemokine CXCL12 is transcriptionally activated by estrogen in estrogen receptor (ER)-positive breast cancer cells. We have found that CXCL12 signaling is essential to maintain the long-term growth of ER-positive breast cancer cells and promotes cancer cell growth in the absence of estrogen. Chronic blockade of CXCL12 signaling with AMD3100, an inhibitor of CXCL12 receptor CXCR4, causes cell death in these cells. Chronic exposure to CXCL12 reprograms ER-positive breast cancer cells through genome-wide transcriptional changes and activates numerous signaling pathways including EMT and the inflammatory response. Many ER target genes are activated in CXCL12-reprogrammed cells even in the absence of estrogen which leads to the diminished estrogen modulated transcription in these cells. These cells also show enhanced signaling via TGFb, EGFR and Rac1 pathways, rendering these cells more sensitive to the CDK7 inhibitor, THZ1, and to drug combinations of THZ1 with the EGFR inhibitor Gefitinib or the RAC1 inhibitor EHT 1864. Furthermore, CXCL12-reprogrammed ER-positive breast cancer cells become more motile in vitro and display a metastatic phenotype in a mouse model. The lung-tropic phenotype of CXCL12-reprogramed MCF-7 cells could be explained by increased expression of integrins and pro-inflammatory signaling molecules. Our novel finding of chronic CXCL12 action on ER-positive breast cancer cells suggests a mechanism by which the interaction between stromal and tumor cells leads to increased breast tumor metastatic potential. Citation Format: Sun J, Slingerland JM, Lippman ME. Chronic CXCL12 exposure induces a metastatic phenotype in ER-positive breast cancer cells through transcriptional reprogramming [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-03-02.
Hospitals must prove beds aren’t needed before closing them, says NHS England
Authors: Gareth Iacobucci
Journal: BMJ (2017)

Local healthcare leaders in England will not be allowed to cut numbers of hospital beds unless they provide evidence that suitable alternative provision is available in the community, the head of NHS England has said.

The requirement is enshrined in three new conditions that local NHS organisations will have to meet if they are planning major hospital bed closures as part of sustainability and transformation plans (STPs). Subject to the current rules that require formal public consultation on service changes, NHS England said that it would approve bed closures only if one of three new conditions is met.

The announcement comes amid concern that some of the 44 STP areas in England plan to cut numbers of hospital beds despite increasing demand for care, in moves branded “lunacy” by the College of Emergency Medicine.1

Announcing the measures at the Nuffield Trust’s health policy …
Dasatinib (SPRYCEL®, BMS-354825) Phase-I/II Study of Patients with Chronic Myeloid Leukemia (CML) Resistant or Intolerant to Imatinib: Results of the CA180031 Study in Japan (Phase I Portion).
Authors: Hisashi Sakamaki, Shin Fujisawa, Kensei Tobinai, Masafumi Taniwaki, Shuichi Miyawaki, Itsuro Jinnai, Atae Utsunomiya, Mistune Tanimoto, Yasuo Morishima, Masaya Okada, Yasushi Miyazaki, Nobuhiko Uoshima, Taku Seriu, Ryuzo Ohno
Journal: Blood (2006)
Posttransplant peripheral blood donor–specific interferon-γ enzyme-linked immune spot assay differentiates risk of subclinical rejection and de novo donor-specific alloantibodies in kidney transplant recipients
Authors: Elena Crespo, Paolo Cravedi, Jaume Martorell, Sergi Luque, Edoardo Melilli, Josep M. Cruzado, Marta Jarque, Maria Meneghini, Anna Manonelles, Chiara Donadei, Núria Lloberas, Montse Gomà, Josep M. Grinyó, Peter Heeger, Oriol Bestard
Journal: Kidney International (2017)
The Cell Cycle in Hematopoietic Stem Cells, Lin−/C-kit+/Sca1+ Fraction, Is Regulated by Connexin 32, Specifically Expressed in the Stem Cell Compartment
Authors: Yoko Hirabayashi, Byung-Il Yoon, Isao Tsuboi, Yan Huo, Yukio Kodama, Jun Kanno, Thomas Ott, James E Trosko, Tohru Inoue
Journal: Blood (2008)