tbuckley/cabot-search huggingface dataset:
Abstract 5091: Inhibiting endothelium directed tumor cell streaming by targeting the HGF/C-Met and EGF/CSF-1 signaling pathways
Authors: Edison Leung, Yarong Wang, Bryan Smith, Daniel Flynn, John Condeelis
Journal: Cancer Research (2015)

Abstract In vivo, tumor cells need to migrate towards blood vessels in order to metastasize. Streaming, a specialized mode of migration involving chemotactic signaling between macrophages and tumor cells, allows linear streams of tumor cells to migrate directionally towards blood vessels on collagen I-containing ECM fibers in vivo. We have successfully reconstructed tumor cell streaming in vitro by co-plating tumors cells, macrophages, and endothelial cells on 2.5 um micro-patterned substrates. We found that tumor cells and macrophages do not demonstrate directional migration in only one direction but random walk. Directional streaming migration of tumor cells in only one direction was established when beads coated with human umbilical vein endothelial cells (HUVEC) were placed at one end of the micro-patterned “collagen fibers” within the assay. Using this in vitro reconstituted streaming system, we found that directional streaming can be blocked by inhibiting multiple signaling pathways - notably the HGF/C-Met signaling pathway between endothelial cells and tumor cells and the EGF/CSF-1 paracrine loop between macrophages and tumor cells. These pathways were blocked using gefitinib (EGFRi), DCC-3014 (CSFRi), and altiratinib (DCC-2701)(c-Meti), which led to a marked decrease in endothelium directed streaming of the tumor cells. The inhibitors showed different efficacies of inhibition of streaming at different distances from the endothelium indicating that HGF from the endothelium organized the random walk of paired macrophages and tumor cells into a directional migration. Key observations made with the in vitro reconstituted system were reproduced in mammary tumors using the in vivo invasion assay. These results highlight a promising role for combinations of these inhibitors in blocking tumor cell streaming and metastasis in vivo and for use in human trials. Citation Format: Edison Leung, Yarong Wang, Bryan Smith, Daniel Flynn, John Condeelis. Inhibiting endothelium directed tumor cell streaming by targeting the HGF/C-Met and EGF/CSF-1 signaling pathways. [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 5091. doi:10.1158/1538-7445.AM2015-5091
Identification of Primitive Subpopulations of Acute Myeloid Leukemia Side Population (SP) Stem Cells Defined by Differentiation Status and Malignant Character.
Authors: Bijan Moshaver, Marjolein A. van der Pol, Guus H. Westra, Nicole Feller, Angele Kelder, Anna van Rhenen, Gert J. Ossenkoppele, Sonja Zweegman, Gerrit J. Schuurhuis
Journal: Blood (2006)
Abstract 5496: Effect of BTK inhibitors on differentiation of human monocyte-derived dendritic cells
Authors: Zhijian Sun, Dongping Zhou, Lusong Luo
Journal: Cancer Research (2015)

Abstract Dendritic cells (DCs) are primary antigen-presenting cells (APCs), which process tumor antigen and present it on the cell surface to the T cells of the adaptive immune system. However, immature DCs facilitate tolerance toward cancer cells. Bruton's tyrosine kinase (BTK) is highly expressed in B cells, monocytes, macrophages and dendritic cells and plays crucial roles in differentiation and activation of myeloid cells. Dendritic cells in Btk−/− mice were reported to have more mature phenotype and stronger in vitro and in vivo T cell stimulatory ability than wild-type DCs. However, the functions of BTK in human DC differencation and maturation were not well characterized. In this study, we revealed the effect of BTK inhibition with ibrutinib, an FDA approved drug for chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), in human monocyte derived dendritic cells (moDCs). We show that BTK was expressed in monocytes and moDCs. BTK activity was regulated during moDCs differencation and BTK inhibitors blocked GM-CSF/IL4 induced activation of BTK. LPS instead of CD40L treatment increased BTK phosphorylation. It was noted that the percentage of CD11c+ MHC IIlow subsets, which represented the immature DCs, was significantly reduced upon ibrutinib treatment during moDC differencation. Meanwhile, ibrutinib dose-dependently increased proportion of CD11c+ MHC IIhigh cells, which represent more mature DCs. We also tested BGB-3111, a more selective BTK inhibitor without ITK, TXK, EGFR, HER2 and JAK3 activity in the same assay. We observed increased MHC II level during differentiation of human moDCs with BGB-3111 treatment. These results support combination strategies for BTK inhibitors with other cancer immunotherapy agents. Citation Format: Zhijian Sun, Dongping Zhou, Lusong Luo. Effect of BTK inhibitors on differentiation of human monocyte-derived dendritic cells. [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 5496. doi:10.1158/1538-7445.AM2015-5496
The Incidence and Outcome of Venous Thrombo-Embolism (VTE) In Non-Small Cell Lung Cancer Patients with Adenocarcinoma Histology In Comparison with Squamous Histology
Authors: Ashwini Bhat, Rakesh Surapaneni, Alexandre Hageboutros, Barry Milcarek, Krystal Hunter, Susan Coakley, Andres Ferber
Journal: Blood (2010)
Tumor Necrosis Factor-a Enhances Human Leukemia Cell Differentiation Induced by DMSO, but Not Retinoic Acid.
Authors: Hong-Nu Yu, Young-Rae Lee, Hyun-Jaung Shim, Myung-Kwan Han, Eun-Kyung Song, Jinny Park, Jong-Suk Kim
Journal: Blood (2005)
Reduced-Intensity Stem Cell Transplantation (RIST) for Non-Hodgkin Lymphoma (NHL): A Single-Institute Experience of 52 Patients.
Authors: Kyoko Sugimoto, Yasushi Onishi, Shigeru Kusumoto, Sung-Won Kim, Masahiro Kami, Shin-ichiro Mori, Yuji Heike, Yoichi Takaue, Kensei Tobinai, Ryuji Tanosaki
Journal: Blood (2004)
Tandem Duplications of the FLT3 and MLL Are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia. AML99 Study in Japan.
Authors: Akira Shimada, Tomohiko Taki, Ken Tabuchi, Takeshi Taketani, Ryoji Hanada, Akio Tawa, Masahiro Tsuchida, Keizo Horibe, Ichiro Tsukimoto, Yasuhide Hayashi
Journal: Blood (2005)
B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells Express Antibodies Reactive with Antigenic Epitopes Expressed on the Surface of Common Bacteria.
Authors: Katerina Hatzi, Rosa Catera, Manlio Ferrarini, Vincent Fischetti, Maxime Herve, Eric Meffre, Charles C. Chu, Nicholas Chiorazzi
Journal: Blood (2006)
Multivariate analysis including biomarkers in the phase III RADIANT-2 study of octreotide LAR plus everolimus (E+O) or placebo (P+O) among patients with advanced neuroendocrine tumors (NET).
Authors: James C. Yao, John D. Hainsworth, Edward M. Wolin, Marianne E. Pavel, Eric Baudin, David Gross, Philippe Ruszniewski, Paola Tomassetti, Ashok Panneerselvam, Stephen Saletan, Judith Klimovsky
Journal: Journal of Clinical Oncology (2012)

4014 Background: In this large phase III trial, median progression-free survival (PFS) improved by 5.1 mo with E+O compared to P+O in patients (pts) with NET associated with carcinoid syndrome. Baseline imbalances including WHO performance status (PS) and primary site favoring P+O confounded primary analysis. Chromogranin A (CgA) and 5-hydroxyindoleacetic acid (5-HIAA) are important biomarkers in NET. Analyses were performed to identify prognostic factors and adjust for baseline imbalances. Methods: Pts were randomized to E+O (n=216) or P+O (n=213). Potential prognostic factors including baseline CgA (≤2×ULN vs &gt;2×ULN), baseline 5-HIAA (≤median vs &gt;median at baseline), age (&lt;65 vs ≥65), gender, race, WHO PS (0 vs 1, 2), primary site (lung vs other), prior somatostatin analog use (yes vs no), duration from diagnosis (&lt;6 mo, 6-24 mo, 2-5 yr, &gt;5 yr), and organs involved (liver, bone) were assessed in univariate analysis using the log rank test and stepwise regression using Cox proportional hazards model. Results: Median PFS (mo) was significantly longer for pts with nonelevated CgA (27 vs 11; p&lt;.001) and nonelevated 5-HIAA (17 vs 11; p&lt;.001). Analyses also indicated age (14 vs 12; p=.01), WHO PS (17 vs 11; p=.004), liver involvement (14 vs not reached; p=.02), bone metastases (8 vs 15; p&lt;.001), and lung as primary site (11 vs 14; p=.06) as potentially prognostic. Multivariate analysis indicated that significant prognostic factors for PFS included baseline CgA (HR, 0.47; CI, 0.34-0.65; p&lt;.001), WHO PS (HR, 0.69; CI, 0.52-0.90; p=.006), bone involvement (HR, 1.52; CI, 1.06-2.18; p=.02), and lung as primary site (HR, 1.55; CI, 1.01-2.36; p=.04). Adjusted for covariates, a 38% reduction in risk of progression was observed for E+O (HR, 0.62; 95% CI, 0.51-0.87; p=.003). Conclusions: In the phase III RADIANT-2 trial, baseline CgA levels, WHO PS, lung as primary site, and bone involvement were important prognostic factors. Exploratory analysis adjusted for these prognostic factors indicated significant benefit of everolimus therapy.
Abstract 917: The modulatory effects of cancer preventive herbal saponins on gut microbiota and mucosal environment in ApcMin/+ mice
Authors: Lei Chen, Manreet Singh, Frederick CC Leung, W.L. Wendy Hsiao
Journal: Cancer Research (2015)

Abstract Human gut harbors 100 trillion microbes that is intrinsically linked to individual's health and diseases, including cancer. Triterpenoid saponins are present in many plants and are major active components in medicinal plants. Gynostemma pentaphyllum (Gp) is consumed as herbal tea as well as herbal medicine and found to possess anti-cancer effects in ApcMin/+ mice in our study. Here, we would like to address whether Gp saponins (GpS) can affect the gut microbiota in the ApcMin/+ colorectal cancer mouse model, and whether the alteration would have cancer preventive implication. Using ERIC-PCR and 16S pyrosequencing analysis, we revealed that GpS treatment altered the overall fecal microbiome. Interestingly, it appeared that GpS treatment enhanced the relatively abundance of the beneficial microbes while reduced the potential harmful sulfate- and sulfur-reducing bacteria lineage. The impact of GpS on the gut mucosal environment was also examined. We found GpS improved the gut barrier function by increasing the numbers of Paneth cells, goblet cells, up-regulating the expression of E-cadherin and down-regulating the expression of N-cadherin in the intestine. In addition, GpS down-regulated the protein expression of beta-catenin and the p-STAT3. Furthermore, higher levels of anti-inflammatory and tissue repair-related cytokines as well as arginase I, but lower level of iNOS expression were found in GpS-treated ApcMin/+ mice. Altogether, GpS might affect the host-microbe interactions by regulating the gut microbial ecosystem and modulating the intestinal mucosal environment, which might contribute to its cancer preventive effect observed in the ApcMin/+ mice. This study was supported by Macau Science and Technology Development Fund 015/2014/A1 and Research Grants Council of Hong Kong under GRF260413 to WL Wendy Hsiao. Citation Format: Lei Chen, Manreet Singh, Frederick CC Leung, W.L. Wendy Hsiao. The modulatory effects of cancer preventive herbal saponins on gut microbiota and mucosal environment in ApcMin/+ mice. [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 917. doi:10.1158/1538-7445.AM2015-917
Analysis of Immunogenetic Factors in Myelodysplastic Syndromes (MDS) Reveals Potential Pathogenic Role Cytokine Genotypes Such as TGF-β.
Authors: Bianca Serio, Ramon Tiu, Ania Jankowska, Zach Nearman, Christine O’Keefe, Mikkael A. Sekeres, Jaroslaw M.D. Maciejewski
Journal: Blood (2007)
Abstract 3069: The role of miR-30c-2* in clinical outcome and drug resistance in HPV-infected non-small cell lung cancer
Authors: Ya-Wen Cheng, Hsiao-Ching Lin
Journal: Cancer Research (2015)

Abstract Lung cancer is leading cause of cancer death in Taiwanese women who are mostly to be life-time never smokers. Majority of drugs and combinations are used to treat with smoking lung cancer patients, not for nonsmokers. However, the 5-year survival rate in lung cancer patients remains ∼15% during the past three decades. Therefore, dissolving tumor recurrence and drug resistance is urgent needed for improving outcome in lung cancer, especially in nonsmokers. Mir-30c-2* has been considered to be tumor suppressor gene in various cancers. MiR-30c-2* levels were associated with in gemcitabine sensitivity of lung cancer cells. Down-regulation of miR-30c promotes tumor invasion via an increased in MTA1 expression. Our previous reports have indicated that HPV16/18 infection may be involved in Taiwanese lung tumorigenesis. Preliminary data showed that miR-30C-2* levels were elevated 45-fold in E6-knockdown TL-1 cells as compared with parental cells with non-specific RNAi tranfection. More interestingly, MTA-1 expression was negatively correlated with miR-30C-2* in lung tumors from lung cancer patients. Expression levels of MTA-1 were positive correlated with tumor stage and nodal metastasis in tumor tissues of lung cancer patients. Our cell model studies also found that miR-30C-2* suppressed by E6 could contribute to tumor metastasis and drug resistance via an increased in MTA-1 expression. These results were showed that miR-30C-2* levels in patients’ tumor tissues could be useful to predict outcome and therapeutic response and to select useful therapy drugs for lung cancer patients, especially in patients with HPV-infection. Citation Format: Ya-Wen Cheng, Hsiao-Ching Lin. The role of miR-30c-2* in clinical outcome and drug resistance in HPV-infected non-small cell lung cancer. [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 3069. doi:10.1158/1538-7445.AM2015-3069
Survival of Newly Diagnosed T-Cell Lymphoma (TCL) in the Modern Era: Investigation of Prognostic Factors with Critical Examination of Therapy in a Multicenter US Cohort.
Authors: Andrew M. Evens, Tatyana Feldman, Aimee Kroll, Lori S. Muffly, Eric Winer, Christopher Flowers, Frederick Lansigan, Chadi Nabhan, Loretta Nastoupil, Austin Kim, Xiuning Li, Kathryn Waksmundzki, David Lam, Jacqueline Tessa Draper, Ashley Meilleur, Rajneesh Nath, Peter Cygan, Jorge J Castillo, Andre Goy, Bruce Woda, Sonali M. Smith, Steven T. Rosen, Jeremy S. Abramson
Journal: Blood (2012)
383. Ancestral AAV Demonstrates Unique Transduction Properties in Mouse and Primate
Authors: Livia S. Carvalho, Ru Xiao, Jason I. Comander, Leo A. Kim, Laurence Lim, Vadim Khaychuck, Eva Plovie, Eric Zinn, Luk H. Vandenberghe
Journal: Molecular Therapy (2015)

Gene therapy is a promising approach in the treatment of inherited and common complex disorders of the retina. Preclinical and clinical studies have validated the use of adeno-associated viral vectors (AAV) as a safe and efficient gene delivery vehicle for subretinal gene transfer. AAV can efficiently target RPE cells and rod and cone photoreceptors but other retinal cell types are more challenging targets. Despite the immune privileged status of the eye we still face some challenges with higher inflammation risks to vector or transgene antigens depending on route of delivery. Studies here aim to build on AAV as a validated platform while exploring new and optimized vector reagents to overcome current limitations for clinical use. We hypothesized that an ancestral AAV species would be less susceptible to pre-existing AAV immunity (PEI) in human populations and confer an improved clinical safety and efficacy profile. We used phylogenetic and bioinformatic methods to infer the ancestral state of AAV and most likely AAV capsid sequences libraries were synthesized and members were evaluated for viral assembly and DNA packaging. Lead candidates were selected and, following subretinal injection into C57Bl/6 mice, retinal tropism was characterized by (a) in vivo transduction by reporter gene expression from fundus imaging, (b) molecular analyses of expression levels, (c) onset of expression and (d) histological profile of targeted retinal cell types. Using synthetic biology methods, in silico reconstructed ancestral AAV capsid sequences were derived and ancestral AAV vectors produced using standard AAV production methods. Ancestral particles, named Anc80, were found to be biochemically similar to existing AAV, stable, and infectious in vitro. In vivo retinal transduction in mice demonstrated a high level of RPE and photoreceptor tropism that is quantitatively higher than AAV8. In addition, onset of expression of Anc80 was visible as early as day 1 post injection and accelerated compared to AAV8. Several variants of Anc80 were evaluated for inner retinal tropism with evidence for improved transduction of Müller glia, RGC, and other inner INL neurons. Preliminary studies in non-human primates also indicate an accelerated onset of expression compared to AAV9 and AAV5. Ancestral AAV have significantly increased resistance to PEI in humans and demonstrate enhanced retinal tropism.
LONG-TERM Outcome of a Fondazione Italiana Linfomi Study Comparing Short Rituximab Maintenance Vs Observation after Brief First-LINE R-FND Chemoimmunotherapy Followed By Rituximab Consolidation in Elderly Patients with Advanced Follicular Lymphoma (FL)
Authors: Carola Boccomini, Marco Ladetto, Francesca Dutto, Simone Ferrero, Luca Baldini, Chiara Bottelli, Claudia Castellino, Annalisa Chiarenza, Annarita Conconi, Federico De Angelis, Andrea Evangelista, Stefan Hohaus, Francesco Merli, Benedetta Puccini, Chiara Rusconi, Eleonora Russo, Stefano Sacchi, Stefano Volpetti, Giuseppe Rossi, Umberto Vitolo
Journal: Blood (2015)
The Assessment of the European Leukemianet Criteria for Clinicohematologic Resistance and Intolerance to Hydroxyurea in Polycythemia Vera Is Not Easily Applicable in Daily Practice
Authors: Laura Fogliatto, Raquel Breunig, Tito Vanelli Costa, Luis Carlos Zanandrea Contin, Juarez Fontoura Silveira, Cinara Silveira, Liane Esteves Daudt, Lucia Silla
Journal: Blood (2014)
47. A Model To Determine the In Vivo Fate of Defined Adenovirus Immune Complexes
Authors: Ramona F. Kratzer, Andrea Hoffmeister, Sigrid Espenlaub, Florian Kreppel
Journal: Molecular Therapy (2015)

Vectors based on Adenovirus type 5 (Ad5) are well suited for the purpose of genetic vaccination due to their high immunogenicity. However, it is known that immune complexes formed upon contact with vector-specific antibodies (Abs) can impede gene transfer and influence vector immune profiles. To model, analyze, and understand the effects of immune complex formation on in vivo biodistribution and vector immunogenicity, we established a novel model based on chemical tagging of Ad capsomers with a carbohydrate epitope. Of note, this model allows to direct antibodies to specific capsid regions and thus to generate highly defined Ad immune complexes independent of species and MHC restrictions. As an artificial immunogenic epitope, we chemically coupled alpha-Gal (Galactose-a1,3-Galactose-b1,4-N-Acetylglucosamine) to specific sites of Ad capsomers. We generated ΔE1 Ad5 vectors being alpha-Galylated at hexon HVR1, hexon HVR5, penton or fiber, and an unmodified control vector. We demonstrated that on account of the alpha-Gal epitope, anti-Gal IgG or IgM bound to selected tagged capsomers. Thus, we analyzed biodistribution and vector-induced immune responses in alpha-1,3-Galactosyltransferase knockout (a1,3-GT KO) mice, which harbor large amounts of anti-Gal Abs. First, to compare the effect of epitope tagging on vector biodistribution, we analyzed hepatic and splenic transgene expression after i.v. injection of alpha-Galylated vectors into anti-Gal-positive a1,3-GT KO mice. We observed that transgene expression from fiber-modified vectors was mildly decreased, while expression from hexon-modified vectors decreased drastically, in a way resembling neutralization. These data suggested that, in fact, our model is suitable to precisely analyze the role of capsomer-specific Ab binding on in vivo vector biodistribution and activity. Furthermore, we analyzed the effect of immune complexation on the induction of vector- and transgene product-directed immune responses after repetitive i.m. delivery of alpha-Galylated vectors into anti-Gal-positive a1,3-GT KO mice. Here, we found that the Ad immune complexes induced transgene product-directed immune responses, even upon repeated vector administration. In particular, the extents of hepatic and splenic transgene expression, and transgene-directed immune responses were inversely correlated. For hexon-modified vectors, in spite of weakest transgene expression, transgene-directed cellular immune responses were strongest. In summary, we showed that alpha-Galylation of Ad capsomers markedly influenced specific immune responses directed to the vector as well as the transgene product. Our concept shall be used as an in vivo model to characterize whether directing or diverting immune complexation to or from specific capsomer sites can improve future strategies for vaccination regimens using Ad vectors.
Assessing Change in Avian Influenza A(H7N9) Virus Infections During the Fourth Epidemic — China, September 2015–August 2016
Authors: Nijuan Xiang, Xiyan Li, Ruiqi Ren, Dayan Wang, Suizan Zhou, Carolyn M. Greene, Ying Song, Lei Zhou, Lei Yang, C. Todd Davis, Ye Zhang, Yali Wang, Jian Zhao, Xiaodan Li, A. Danielle Iuliano, Fiona Havers, Sonja J. Olsen, Timothy M. Uyeki, Eduardo Azziz-Baumgartner, Susan Trock, Bo Liu, Haitian Sui, Xu Huang, Yanping Zhang, Daxin Ni, Zijian Feng, Yuelong Shu, Qun Li
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Abbreviations: IQR = interquartile range; LPM = live-poultry market.* Significant difference between Epidemic 4 and Epidemics 1-3 (p<0.05).† Other occupations include laborers, persons working in government or government-affiliated institutions, business service providers, children, and students.§ Illness with any one of following: chest radiograph indicative of multilobar lesions or >50% increase in size of lesions within a 48-hour period; dyspnea or respiratory rate >24 times per minute for adults; severe hypoxia defined as <92% oxygen saturation while receiving 3-5 liters of supplemental oxygen per minute; or shock, acute respiratory distress syndrome, or multiple organ dysfunction syndrome.
Abdominal vs Minimally Invasive Hysterectomy
Authors: Elizabeth A. Pritts, David L. Olive, Dan Clarke-Pearson
Journal: JAMA (2016)

To the Editor We disagree with the analysis and conclusions of the Research Letter by Dr Wright and colleagues,1 which described hysterectomy complication rates before and after the 2014 US Food and Drug Administration (FDA) guidance regarding electric power morcellation for gynecologic surgery.