tbuckley/cabot-search huggingface dataset:
Characteristics of Patients (Pts) with Chronic Lymphocytic Leukemia (CLL) Receiving Rituximab Monotherapy in the Connect® CLL Registry
Authors: Jeff Sharman, Matthew Davids, Charles Michael Farber, David L. Grinblatt, Neil E. Kay, Nicole Lamanna, Anthony R. Mato, Chadi Nabhan, Kristen Sullivan, E. Dawn Flick, Pavel Kiselev, Shriya Bhushan, Arlene S. Swern, Christopher R. Flowers
Journal: Blood (2016)
CXCL14 is a candidate biomarker for Hedgehog signalling in idiopathic pulmonary fibrosis
Authors: Guiquan Jia, Sanjay Chandriani, Alexander R Abbas, Daryle J DePianto, Elsa N N'Diaye, Murat B Yaylaoglu, Heather M Moore, Ivan Peng, Jason DeVoss, Harold R Collard, Paul J Wolters, Jackson G Egen, Joseph R Arron
Journal: Thorax (2017)

<h3>Background</h3> Idiopathic pulmonary fibrosis (IPF) is associated with aberrant expression of developmental pathways, including Hedgehog (Hh). As Hh signalling contributes to multiple pro-fibrotic processes, Hh inhibition may represent a therapeutic option for IPF. However, no non-invasive biomarkers are available to monitor lung Hh activity. <h3>Methods</h3> We assessed gene and protein expression in IPF and control lung biopsies, mouse lung, fibroblasts stimulated in vitro with sonic hedgehog (SHh), and plasma in IPF patients versus controls, and cancer patients before and after treatment with vismodegib, a Hh inhibitor. <h3>Results</h3> Lung tissue from IPF patients exhibited significantly greater expression of Hh-related genes versus controls. The gene most significantly upregulated in both IPF lung biopsies and fibroblasts stimulated in vitro with SHh was <i>CXCL14</i>, which encodes a soluble secreted chemokine whose expression is inhibited in vitro by the addition of vismodegib. <i>CXCL14</i> expression was induced by SHh overexpression in mouse lung. Circulating CXCL14 protein levels were significantly higher in plasma from IPF patients than controls. In cancer patients, circulating CXCL14 levels were significantly reduced upon vismodegib treatment. <h3>Conclusions</h3> CXCL14 is a systemic biomarker that could be used to identify IPF patients with increased Hh pathway activity and monitor the pharmacodynamic effects of Hh antagonist therapy in IPF. <h3>Trial registration number</h3> Post-results, NCT00968981.
Abstract P2-03-07: Exome sequencing of human breast cancer tissues resistant to taxanes
Authors: Y Endo, Y Dong, N Kondo, Y Hato, T Hisada, M Nishimoto, S Nishikawa, S Takahashi, T Toyama
Journal: Cancer Research (2017)

Abstract Background: Although taxanes are a mainstay of breast cancer treatment, some cases are resistant to these drugs. This is a crucial issue in breast cancer therapy. In the emerging era of next-generation sequencing, it is possible to obtain extensive genomic information on individual tumors in a very short time. Using this technology, it was reported that specific mutations might affect therapeutic efficacy and induce resistance to specific treatment. Objective: The aim of this study was to investigate the mechanisms of taxane resistance using whole exon sequencing and expression analyses in human breast cancer tissues. Materials and Methods: We selected six breast cancer patients whose tumors responded well to anthracycline treatment but suffered disease progression on taxane treatment. We then performed whole exon sequencing on these samples using HiSeq (Illumia). In this way, we identified somatic mutations of candidate genes considered to be instrumental for mediating resistance to taxanes. Next, we performed mRNA expression analyses of these candidate genes in a further 122 breast cancers treated with taxanes at our institute. Finally, we correlated mRNA expression levels of these genes with clinicopathological factors and prognosis. Results: We identified 9 mutations common to all 6 patients analyzed in this study, and a further 16 mutations shared by 5 of them. Kaplan-Meier analyses showed that high level mRNA expression of 3 of these 25 genes was significantly associated with poorer disease-free survival. Moreover, high level mRNA expression of one of these three genes was significantly associated with worse overall survival. However, there were no significant correlations between expression levels of these three genes and any clinicopathologeical features. Conclusion: Using next-generation sequencing, we have identified three candidate genes involved in resistance to taxane treatment in breast cancer. We are now analyzing the functional attributes of these three genes. Citation Format: Endo Y, Dong Y, Kondo N, Hato Y, Hisada T, Nishimoto M, Nishikawa S, Takahashi S, Toyama T. Exome sequencing of human breast cancer tissues resistant to taxanes [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 P2-03-07.
Abstract P5-06-08: <i>BRCA1</i> promoter hypermethylation, but not BRCA1 expression, is associated with basal-like features and good prognosis in triple negative breast cancer
Authors: W Jacot, J Simony-Lafontaine, C Mollevi, F Boissierre, E Lopez-Crapez, E Chartron, P-J Lamy, S Guiu
Journal: Cancer Research (2017)

Abstract Purpose: BRCA1 gene mutation is closely associated with familial hereditary breast cancer. Decreased expression of BRCA1 could be detected in certain types of sporadic breast cancer without BRCA1 mutations. Aberrant hypermethylation of DNA promoter CpG islands is one of the mechanisms by which tumor suppressor gene expression and function could be lost. We investigated BRCA1 methylation status and BRCA1 immunohistochemistry (IHC) expression and their clinic-pathological significance in triple negative breast cancers (TNBC). Patients and methods: We analyzed BRCA1 promoter hypermethylation using a methylation specific PCR assay and BRCA1 IHC expression using the MS110 monoclonal antibody and Garg and Meisel scoring classification. Their clinicopathological and prognostic implications were analyzed in a TMA of TNBC samples from European patients. Results: To date, 123 TNBC have been analyzed. 25 tumors (20%) presented a BRCA1 promoter hypermethylation. BRCA1 IHC expression was retained, equivocal and lost in 73 (59%), 17 (14%) and 33 (27%) cases respectively. No significant correlation was found between promoter hypermethylation and protein expression (p=0.28). A significant association was found between promoter hypermethylation and basal staining (CK5/6 and/or EGFR IHC staining), while using either a 10% or 1% cut-off for basal definition (p= 0.04 and 0.03, respectively). No significant association was found between BRCA1 expression and a basal phenotype. With a median follow-up of 6.3 years (range [0.01 – 11.8]), 35 relapses and deaths occurred (71.2% 5-years RFS and 77.8 5-years OS). RFS was significantly associated with T and N stage, and a trend was seen for a better prognosis of BRCA1 promoter hypermethylated tumors (5-years RFS: 84% vs. 68%, p=0.07). OS was significantly associated with T and N stage, and adjuvant chemotherapy. Conclusion: BRCA1 promoter hypermethylation is associated with basal-like features and seems to be associated with a better prognosis in TNBC. BRCA1 IHC expression is not a good surrogate marker for evaluation of the methylation status of the tumors, and did not appear associated with prognosis in our series. The data will be updated for the meeting in term of number of analyzed tumors in order to strengthen the statistical analysis. Citation Format: Jacot W, Simony-Lafontaine J, Mollevi C, Boissierre F, Lopez-Crapez E, Chartron E, Lamy P-J, Guiu S. BRCA1 promoter hypermethylation, but not BRCA1 expression, is associated with basal-like features and good prognosis in triple negative breast cancer [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 P5-06-08.
Surface Expression of CRLF2 Protein Is Associated with Lower Minimal Residual Disease (MRD) Among Children with IKZF1-deleted Acute Lymphoblastic Leukemia (ALL)
Authors: Agata Pastorczak, Lukasz Sedek, Marcin Braun, Joanna Madzio, Alicja Sonsala, Marta Bielska, Joanna Taha, Patryk Gorniak, Edyta Ulinska, Michal Matysiak, Katarzyna Derwich, Monika Lejman, Jerzy Kowalczyk, Wanda Badowska, Maciej Niedzwiecki, Bernarda Kazanowska, Tomasz Szczepanski, Wojciech Mlynarski
Journal: Blood (2014)
Part I: Main Lectures Hauptvorträge Rapports principaux
Authors: T.F. Main, E.J. Anthony, M. Fordham, Anna Freud, Annemarie Dührssen, R.D. Laing, J. Ruesch, M. Boss, G. Benedetti, Elizabeth R. Zetzel, J.D. Sutherland, Dorothy Stock Whitaker, E.K. Schwartz, S.H. Foulkes, F. Knobloch, J. Cumming, Elaine Cumming, Isabel E.P. Menzies, Doreen Weddell, Ch. Mertens de Wilmars, E.L. Trist, D.H. Clark, A.H. Stanton
Journal: Psychotherapy and Psychosomatics (1965)
Frequency and Prognostic Impact of NUP98/NSD1 Translocations in Adult AML and MDS Patients
Authors: Felicitas Thol, Britta Kölking, Iris H.I.M. Hollink, Frederik Damm, Marry M. van den Heuvel-Eibrink, C. Michel Zwaan, Gesine Bug, Oliver G. Ottmann, Katharina Wagner, Michael A Morgan, Wolf-Karsten Hofmann, Gudrun Göhring, Brigitte Schlegelberger, Jürgen Krauter, Arnold Ganser, Michael Heuser
Journal: Blood (2012)
Expression and Functional Differences of CBFA2T (ETO, MTG) Gene Family Members in Hematopoiesis.
Authors: Fariborz Mortazavi, ShriHari Kadkol, Annette Bruno, Kristine Baraoidan, Steven Ackerman, Amittha Wickrema, Yogenthiran Saunthararajah
Journal: Blood (2004)
Abstract P3-13-26: Deep Infrared Imaging to identify venous impairment after breast cancer surgery
Authors: J-P Belgrado, L Vandermeeren, S Vankerckhove, J-B Valsamis, V Feipel, M Rooze, J-J Moraine, D Hertens, B Carly, F Liebens
Journal: Cancer Research (2017)

Abstract This abstract was not presented at the symposium.
Is Type of Monosomy (Total or Partial) Crucial for Prognostic Value of Monosomal Karyotype in AML Patients? – Preliminary Results of Retrospective Polish Adult Leukemia Group (PALG) Study,
Authors: Ewa Wawrzyniak, Agnieszka Wierzbowska, Kotkowsa Aleksandra, Monika Siemieniuk-Rys, Joanna Kosny, Aleksandra Golos, Agnieszka Pluta, Tadeusz Robak, Wanda Knopinska-Posluszny, Agnieszka Klonowska, Mariola Iliszko, Andrzej Hellmann, Renata Woroniecka, Barbara Pienkowska-Grela, Anna Ejduk, Krzysztof Warzocha, Malgorzata Wach, Anna Dmoszynska, Ewa Duszenko, Anna Jaskowiec, Malgorzata Jakobczyk, Barbara Mucha, Sebastian Grosicki, Jerzy Holowiecki, Olga Haus
Journal: Blood (2011)
Ovatodiolide suppresses colon tumorigenesis and prevents polarization of M2 tumor-associated macrophages through YAP oncogenic pathways
Authors: Yan-Jiun Huang, Ching-Kuo Yang, Po-Li Wei, Thanh-Tuan Huynh, Jacqueline Whang-Peng, Tzu-Ching Meng, Michael Hsiao, Yew-Ming Tzeng, Alexander TH Wu, Yun Yen
Journal: Journal of Hematology & Oncology (2017)

An increased expression of Yes-associated protein (YAP1) has been shown to promote tumorigenesis in many cancer types including colon. However, the role of YAP1 in promoting colon tumorigenesis remains unclear. Here, we demonstrate that YAP1 expression is associated with M2 tumor-associated macrophage polarization and the generation of colon cancer stem-like cells. YAP1 downregulation by gene silencing or a phytochemical, ovatodiolide, not only suppresses colon cancer tumorigenesis but also prevents M2 TAM polarization. Human monocytic cells, THP-1, and colon cancer cell lines, HCT116 and DLD-1, were co-cultured to mimic the interactions between tumor and its microenvironment. M2 polarization of the THP-1 cells were examined using both flow cytometry and q-PCR technique. The inhibition of YAP1 signaling was achieved by gene-silencing technique or ovatodiolide. The molecular consequences of YAP1 inhibition was demonstrated via colony formation, migration, and colon-sphere formation assays. 5-FU and ovatodiolide were used in drug combination studies. Xenograft and syngeneic mouse models were used to investigate the role of YAP1 in colon tumorigenesis and TAM generation. An increased YAP1 expression was found to be associated with a poor prognosis in patients with colon cancer using bioinformatics approach. We showed an increased YAP1 expression in the colon spheres, and colon cancer cells co-cultured with M2 TAMs. YAP1-silencing led to the concomitant decreased expression of major oncogenic pathways including Kras, mTOR, β-catenin, and M2-promoting IL-4 and tumor-promoting IL-6 cytokines. TAM co-cultured colon spheres showed a significantly higher tumor-initiating ability in vivo. Ovatodiolide treatment alone and in combination with 5-FU significantly suppressed in vivo tumorigenesis and less TAM infiltration in CT26 syngeneic mouse model. We have identified the dual function of YAP1 where its suppression not only inhibited tumorigenesis but also prevented the generation of cancer stem-like cells and M2 TAM polarization. Ovatodiolide treatment suppressed YAP1 oncogenic pathways to inhibit colon tumorigenesis and M2 TAM generation both in vitro and in vivo. Ovatodiolide should be considered for its potential for adjuvant therapeutic development.
NFIB: A Gene Consistently Upregulated in MPD and Frequently Co-Amplified with JAK2V617F Augments Growth of Erythropoietin Dependent Cells
Authors: Xiaoqing Lin, Monica Buzzai, Ross L Levine, Windy Berkofsky-Fessler, Weijia Zhang, Benjamin L. Ebert, D. Gary Gilliland, Jonathan D. Licht
Journal: Blood (2008)
Barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review of qualitative literature
Authors: Sophia G de Vries, Anne L Cremers, Charlotte C Heuvelings, Patrick F Greve, Benjamin J Visser, Sabine Bélard, Saskia Janssen, René Spijker, Beth Shaw, Ruaraidh A Hill, Alimuddin Zumla, Marieke J van der Werf, Andreas Sandgren, Martin P Grobusch
Journal: The Lancet Infectious Diseases (2017)
Erratum: Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma
Authors: I Breitkreutz, M S Raab, S Vallet, T Hideshima, N Raje, C Mitsiades, D Chauhan, Y Okawa, N C Munshi, P G Richardson, K C Anderson
Journal: Leukemia (2008)
CD11b activation suppresses TLR-dependent inflammation and autoimmunity in systemic lupus erythematosus
Authors: Mohd Hafeez Faridi, Samia Q. Khan, Wenpu Zhao, Ha Won Lee, Mehmet M. Altintas, Kun Zhang, Vinay Kumar, Andrew R. Armstrong, Carmelo Carmona-Rivera, Jessica M. Dorschner, Abigail M. Schnaith, Xiaobo Li, Yogita Ghodke-Puranik, Erica Moore, Monica Purmalek, Jorge Irizarry-Caro, Tingting Zhang, Rachael Day, Darren Stoub, Victoria Hoffmann, Shehryar Jehangir Khaliqdina, Prachal Bhargava, Ana M. Santander, Marta Torroella-Kouri, Biju Issac, David J. Cimbaluk, Andrew Zloza, Rajeev Prabhakar, Shashank Deep, Meenakshi Jolly, Kwi Hye Koh, Jonathan S. Reichner, Elizabeth M. Bradshaw, JianFeng Chen, Luis F. Moita, Peter S. Yuen, Wanxia Li Tsai, Bhupinder Singh, Jochen Reiser, Swapan K. Nath, Timothy B. Niewold, Roberto I. Vazquez-Padron, Mariana J. Kaplan, Vineet Gupta
Journal: Journal of Clinical Investigation (2017)

Genetic variations in the ITGAM gene (encoding CD11b) strongly associate with risk for systemic lupus erythematosus (SLE). Here we have shown that 3 nonsynonymous ITGAM variants that produce defective CD11b associate with elevated levels of type I interferon (IFN-I) in lupus, suggesting a direct link between reduced CD11b activity and the chronically increased inflammatory status in patients. Treatment with the small-molecule CD11b agonist LA1 led to partial integrin activation, reduced IFN-I responses in WT but not CD11b-deficient mice, and protected lupus-prone MRL/Lpr mice from end-organ injury. CD11b activation reduced TLR-dependent proinflammatory signaling in leukocytes and suppressed IFN-I signaling via an AKT/FOXO3/IFN regulatory factor 3/7 pathway. TLR-stimulated macrophages from CD11B SNP carriers showed increased basal expression of IFN regulatory factor 7 (IRF7) and IFN-β, as well as increased nuclear exclusion of FOXO3, which was suppressed by LA1-dependent activation of CD11b. This suggests that pharmacologic activation of CD11b could be a potential mechanism for developing SLE therapeutics.
Dissecting the Genetic Basis of Marginal Zone Lymphoma Reveals a Predilection for NF-Kb Activation by Clonal MZL Located at Extranodal Sites
Authors: Esteban Braggio, Ahmet Dogan, Wee-Joo Chng, Jonathan J Keats, Julie Marie Matthews, Izidore S Lossos, Thomas E. Witzig, Rafael Fonseca
Journal: Blood (2010)
Delta-1 Promotes Soluble IL-6R-Mediated Action of IL-6 on Human Erythropoiesis While Counteracting the Effect of IL-6 on the Generation of Myeloid-Lineage Cells.
Authors: Kentaro Yamamura, Kohshi Ohishi, Naoyuki Katayama, Hiroshi Shiku, Mitsuo Nishikawa, Tatsutoshi Nakahata
Journal: Blood (2005)
Abstract P3-17-02: Gene expression differences between ductal carcinoma in situ with and without progression to invasive breast cancer
Authors: SC Doebar, AM Sieuwerts, V de Weerd, JWM Martens, CHM van Deurzen
Journal: Cancer Research (2017)

Abstract Background The mechanism behind progression of ductal carcinoma in situ (DCIS) to invasive breast cancer (IBC) remains unknown. The aim of our study was to increase our understanding regarding molecular alterations driving DCIS progression by comparing gene-expression patterns between patients with pure DCIS and patients with synchronous DCIS and IBC. Methods In this retrospective study, we included patients with extensive pure DCIS (n=12), defined as &amp;gt; 5 cm, as a representation of biologically indolent lesions with limited invasive capacity. These cases were matched with patients with a limited DCIS component, defined as &amp;lt; 1 cm, and synchronous IBC (n=12), representing lesions with a high invasive potential. Matching was based on age and surrogate DCIS subtypes. Gene expression profiling, using 93 tumor-specific target genes, was performed to identify transcriptional differences between the DCIS components of these two groups. The identified genes were validated by immunohistochemistry. Results In total, for 9 genes there was a significant difference in gene expression between patients with pure DCIS and patients with DCIS and synchronous IBC. The majority of these 9 genes were significantly higher expressed in DCIS samples with IBC, including PLAU (P=0.002), COL1A1 (P=0.006), KRT81 (P=0.009), S100A7 (P=0.015), SCGB1D2 (P=0.023), KRT18 (P=0.029) and NOTCH3 (P= 0.044), while EGFR and CXCL14 showed a significantly higher expression in pure DCIS (P=0.015 and P=0.028 respectively). Based on these 9 genes, unsupervised hierarchical clustering-analysis revealed distinct clustering of patients with pure DCIS and patients with DCIS and synchronous IBC. Immunohistochemical analyses are in progress. Conclusion This pilot study suggests that patients with pure DCIS have a significant different gene expression pattern as compared to patients with DCIS and synchronous IBC. If these results can be validated in an independent cohort, these differently expressed genes could be used to predict progression in individual patients diagnosed with DCIS. Furthermore, these genes may pinpoint driver pathway(s) that play an important role in the progression of DCIS to IBC. Citation Format: Doebar SC, Sieuwerts AM, de Weerd V, Martens JWM, van Deurzen CHM. Gene expression differences between ductal carcinoma in situ with and without progression to invasive breast cancer [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 P3-17-02.
Comparison of Therapeutic Effect between Related Donor and Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) in the Treatment of Leukemia.
Authors: Qifa Liu, Kai Yang, Zhiping Fan, Jing Sun, Dan Xu, Yongqiang Wei, Yu Zhang, Fanyi Meng
Journal: Blood (2006)
Abstract DL-1: Targeting breast cancer stem cells: Challenges and opportunities
Authors: MS Wicha
Journal: Cancer Research (2017)

Abstract Breast cancers contain cell populations that display hierarchical organization at the apex of which are cells that display stem cell properties. These cancer stem cells (CSCs) mediate metastasis and contribute to treatment resistance. CSC's display cellular plasticity , a property that allows them to transition between mesenchymal and epithelial states, facilitating metastasis. Although different therapeutic strategies have been developed for the treatment of the various molecular subtypes of breast cancer, CSCs driving these cancers may share common regulatory pathways including those maintaining cellular plasticity. This suggests that therapeutic strategies targeting these CSC pathways may be complementary to subtype specific therapeutic agents targeting bulk cell populations. Furthermore, since CSCs constitute a minor fraction of total tumor cell populations classical clinical endpoints such as tumor regression are inadequate to assess the efficacy of CSC targeting therapeutics. Neoadjuvant trial designs allow for the direct assessment of treatment on biological targets and as well as the therapeutic effectiveness of CSC targeting agents. Molecular analysis of circulating tumor cells at single cell resolution provides an alternative method of accessing the effects of CSC targeting therapies. CSCs are regulated by the tumor micro environment and recent studies suggest that the immune microenvironment plays a crucial role in CSC regulation. Immunotherapeutic approaches may provide a means to target heterogeneous CSC's as well as bulk tumor populations. Early phase clinical trials currently in progress have demonstrated the safety of CSC targeting agents. Future randomized trials will be required to determine whether addition of CSC targeting therapeutics to current agents targeting bulk cell populations improves the efficacy of these therapeutic agents. Citation Format: Wicha MS. Targeting breast cancer stem cells: Challenges and opportunities [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 DL-1.
Salvage Therapy with Combined Cyclophosphamide (C), Fludarabine (F), Alemtuzumab (A), and Rituximab (R) (CFAR) for Heavily Pre-Treated Patients with CLL.
Authors: William G. Wierda, S. OBrien, A. Ferrajoli, S. Faderl, C. Koller, F. Giles, J. Cortes, D. Thomas, F. Ravandi, G. Garcia-Manero, M. Andreeff, S. Lerner, H. Kantarjian, M. Keating
Journal: Blood (2005)