tbuckley/cabot-search huggingface dataset:
Abstract 2195: A high-throughput chemical screen identifies synergistic activity between crizotinib and transcriptional CDK inhibitors in ALK-mutated neuroblastoma
Authors: Nathan F. Moore, Edmond Chipumuro, Clark M. Hatheway, Tinghu Zhang, Nathanael S. Gray, Rani E. George
Journal: Cancer Research (2015)

Abstract Activating mutations in the anaplastic lymphoma receptor tyrosine kinase (ALK) represent important therapeutic targets in neuroblastoma (NB). One of the more common mutations, ALKF1174L, is sensitive to the FDA-approved ALK inhibitor, crizotinib, only at high doses and mediates acquired resistance to crizotinib in ALK-rearranged cancers. To identify compounds that would potentiate the effect of crizotinib, we performed a high-throughput compound screen using ALKF1174L-dependent human NB SH-SY5Y cells and compared viability between cells treated with the screen compound alone and in combination with crizotinib. The strongest “hits” among the ∼8,000 compounds screened were inhibitors of cyclin dependent kinases (CDKs). The combination of crizotinib and two candidate pan-selective CDK inhibitors, AT7519 and SNS-032 resulted in synergistic activity with significantly increased apoptosis over that of either single agent alone. This effect was observed in NB cells expressing not only ALKF1174L, but also in those expressing ALKR1275Q, the most common NB-associated ALK mutation. Synergy was also seen with ceritinib (LDK378), a structurally unrelated ALK inhibitor, in combination with both AT7519 and SNS-032. We determined that the synergistic effect was mediated preferentially through the transcriptional, rather than the cell cycle activity of these CDK inhibitors, denoted by absence of cell cycle arrest, stalling of RNA polymerase II at representative gene promoters, and loss of Pol II phosphorylation at the transcription elongation marker serine 2 in treated cells. These findings were comparable with results obtained using agents that were highly selective for CDK9 or CDK7, CDKs with roles in transcription regulation. Finally, in murine xenogaft models of ALK-mutated NB, the combination resulted in inhibition of tumor growth and prolongation of survival compared to single agents alone. Together, these data support further pre-clinical and clinical efforts to explore the therapeutic potential of combining ALK inhibitors with transcriptional CDK inhibitors in ALK-mutated NB. Citation Format: Nathan F. Moore, Edmond Chipumuro, Clark M. Hatheway, Tinghu Zhang, Nathanael S. Gray, Rani E. George. A high-throughput chemical screen identifies synergistic activity between crizotinib and transcriptional CDK inhibitors in ALK-mutated neuroblastoma. [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 2195. doi:10.1158/1538-7445.AM2015-2195
Medicare Payment for Behavioral Health Integration
Authors: Matthew J. Press, Ryan Howe, Michael Schoenbaum, Sean Cavanaugh, Ann Marshall, Lindsey Baldwin, Patrick H. Conway
Journal: New England Journal of Medicine (2016)

Four new codes have been created for the 2017 Medicare Physician Fee Schedule to allow payment to health care providers for furnishing services that integrate behavioral health care with primary care — an effective strategy for improving patient outcomes.
Abstract 2729: Chronic stress promotes lung cancer development via IGF-1R pathway
Authors: Hyun-Ji Jang, Hye-Jin Boo, Yujin Jung, Hye-Young Min, Ho-Young Lee
Journal: Cancer Research (2015)

Abstract Lung cancer is a leading cause of cancer death worldwide. Although smoking is a main cause, approximately 25% of lung cancer cases are not attributable to tobacco use. Epidemiological studies strongly suggest that chronic stress influences cancer development and progression. Recent mechanistic studies showed that biological signaling pathways could contribute to such effects. But the underlying mechanisms for the association between chronic stress and lung cancer development are poorly understood. The purpose of this study is to investigate whether chronic stress can induce lung cancer development and, if so, what is the mechanism underlying the chronic stress-induced lung cancer development. We observed that stress hormone, norepinephrine (NE) increased cell viability in the absence of growth factors, foci formation, and colony formation in human bronchial epithelial cells and activated the type 1 insulin-like growth factor receptor (IGF-1R) pathway. We found that chronic stress resulted in high levels of NE in serum, activation of IGF-1R in lung tissue and promoted urethane-induced lung tumor formation in vivo. Moreover, inhibition of the IGF-1R pathway suppressed NE-induced transformed phenotypes in vitro. We further confirmed that chronic stress-induced lung tumor formation was greater in mice carrying lung-specific human IGF-1R transgene (Tg) than in wild type mice. Our results indicate that chronic stress may promote lung cancer development via the IGF-1R pathway, suggesting that IGF-1R is an effective target for the chemoprevention of stress-induced lung cancer. Citation Format: Hyun-Ji Jang, Hye-Jin Boo, Yujin Jung, Hye-Young Min, Ho-Young Lee. Chronic stress promotes lung cancer development via IGF-1R pathway. [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 2729. doi:10.1158/1538-7445.AM2015-2729
Rituximab Treatment for Recalcitrant Dermatitis Herpetiformis
Authors: Lauren N. Albers, John J. Zone, Benjamin K. Stoff, Ron J. Feldman
Journal: JAMA Dermatology (2016)

Dermatitis herpetiformis (DH) is an autoimmune blistering condition seen in the context of celiac disease. While typically managed by gluten-free diet and dapsone, treatment of DH refractory to standard treatments is not well defined.A man in his 80s with DH not controlled by gluten-free diet (with poor adherence), dapsone, and conventional immune-suppressing agents responded to treatment with rituximab according to the lymphoma protocol (4 weekly infusions of 375 mg/m2). Thirteen months after treatment, the patient had achieved complete resolution of pruritus and clinical manifestations of the disease, as well as normalization of antibodies against epidermal and tissue transglutaminases. He achieved complete clinical and serological remission and has remained symptom-free up to 18 months following treatment.We present here the first case of a patient with DH treated with rituximab who achieved complete clinical and serological remission. We suggest rituximab as a viable treatment option for recalcitrant DH.
New Insights to the MLL Recombinome Including 8 Novel Partner Genes ACTN4, C2CD3, DCP1A, FLNA, LAMC3, LOC100128568, NRIP3, and TNRC18.
Authors: Claus Meyer, Eric Kowarz, Julia Hofmann, Thomas Fischer, Sara El Ashkar, Andrea Teigler-Schlegel, Brian Balgobind, Thomas Burmeister, Etienne De Braekeleer, Eric Delabesse, Aline Renneville, Theo Dingermann, Thomas Klingebiel, Rolf Marschalek
Journal: Blood (2008)
Extracellular Nucleoside Diphosphate Kinase NDPK/Nm23 Protein Isoforms A and B Support Erythropoiesis and Have a Burst-Promoting Activity.
Authors: Zwi N. Berneman, Roel Willems, Griet Nijs, Marc Lenjou, Dirk R. Van Bockstaele
Journal: Blood (2004)
Stable core virome despite variable microbiome after fecal transfer
Authors: Felix Broecker, Giancarlo Russo, Jochen Klumpp, Karin Moelling
Journal: Gut Microbes (2016)

We recently described the 4.5-year time course of the enteric bacterial microbiota and virome of a patient cured from recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT). Here, we extended the virome analyses and found the patient's phage population to exhibit highly donor-similar characteristics following FMT, which remained stable for the whole period tested (up to 7 months). Moreover, the detected viral populations of donor and patient exhibited comparable diversity and richness. These findings were unexpected since enteric viromes are normally highly variable, assumed to influence the bacterial host community and change with environmental conditions. In contrast to the virome, the bacterial microbiota varied indeed for more than 7 months with ongoing dysbiosis before it reached donor similarity. Our findings that are based on sequence information and protein domain analysis seem to suggest that stable phage properties correlate with successful FMT better than the changing bacterial communities. We speculate that we here preferentially detected a stable core virome, which dominated over a variable flexible virome that may have been too heterogeneous for experimental detection or was underrepresented in the databases. It will be interesting to analyze whether the enteric virome allows predictions for the clinical outcome of FMT for rCDI and other diseases such as inflammatory bowel disease or obesity.
Abstract 1050: Effects of 5-hydroxymethylcytosine epigenetic modification on G-quadruplex and i-motif structure and stability within the VEGF promoter
Authors: Rhianna Morgan, Randy Wadkins, Tracy Brooks
Journal: Cancer Research (2015)

Abstract CpG islands are prone to epigenetic cytosine modification via methylation (5mC) or 5-hydroxymethylation (5hmC). Although their potential sequences and regions for occurrence in G/C-rich DNA overlap, throughout the genome 5mC and 5hmC, and 5mC and G-quadruplex (G4) and i-motif (iM) structures, are found to not be co-existent. Moreover, in some regions of DNA, 5hmCs and G4/iM forming regions have high potential to form in concurrence. However, minimal research has been done examining the effect of 5hmC incorporation into G4 and iMs in order to determine the effect of cytosine modification on non-B-DNA structures. These higher order secondary DNA formations have been described within the VEGF promoter and have great potential to silence its transcription and prevent subsequent angiogenesis. In addition, there are three cytosines in the promoter on both the guanine- and the cytosine-rich strands found in CpG sequences that have the potential for 5mhC modification. Therefore, the current study was undertaken to examine the whether there is an effect of 5hmC incorporation into G4 loops and iM stems on structure formation and stabilization. Significant changes in structure or stability in buffers with varying pH’s, cationic strength, and molecular crowding conditions were examined by circular dichroism and confirmed by UV-monitored melting. Electromobility shift assays differentiated inter- and intra-molecular structures, further identifying the number of isoforms. Notable changes in G4 dynamics were seen with two of the three loop modifications, which decreased overall stability and increased intermolecular structures. Much less marked effects were discovered for the iM structures. Ongoing studies examining the role of G4 and iM 5hmC incorporation in regulation by endogenous proteins are part of a global effort to best understand the physiological conditions regulating G4 and iM stability and function. These VEGF promoter higher order structures are promising therapeutic targets for anti-angiogenic therapy, and a comprehensive understanding of the physiological principles governing their formation will best inform future drug discovery efforts. Brooks Lab startup funds, R15, University of Mississippi School of Pharmacy Citation Format: Rhianna Morgan, Randy Wadkins, Tracy Brooks. Effects of 5-hydroxymethylcytosine epigenetic modification on G-quadruplex and i-motif structure and stability within the VEGF promoter. [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 1050. doi:10.1158/1538-7445.AM2015-1050
Abstract 1581: A study of pulmonary and peripheral vein blood as sources of circulating tumor cells in early lung cancer
Authors: Vasudha Murlidhar, Rishindra M. Reddy, Ebrahim Azizi, Lili Zhao, Svetlana Grabauskiene, Zhuo Zhang, Nithya Ramnath, Jules Lin, Andrew C. Chang, Philip W. Carrott, William R. Lynch, Mark B. Orringer, Max S. Wicha, Nallasivam Palanisamy, David G. Beer, Sunitha Nagrath
Journal: Cancer Research (2015)

Abstract Lung cancer is one of the most prevalent cancers world-wide. It is usually diagnosed at an advanced stage with low survival rates. Early detection and intervention can have a profound impact in improving survival. Circulating tumor cells (CTCs), or cells shed by the tumor into the blood circulation, offer a less invasive method of tumor biopsy. Surgical lobectomy for early stage lung cancers provides access to the pulmonary vein (PV) draining the affected lobe, and is presumably an enriched source of CTCs shed by the primary lung tumor. Analyzing peripheral (Pe) and pulmonary vein (PV) blood combined could potentially shed light onto optimal markers and disease progression. We hypothesize that blood from the pulmonary vein has a higher abundance of CTCs than peripheral blood, thereby providing a larger yield of CTCs from early lung cancer patients for downstream analysis. A cohort of greater than 30 lung cancer patients was enrolled in a pilot study. PV and Pe blood specimens from these patients were obtained at different time points in the perioperative time period, and were processed through a high-throughput microfluidic device, the OncoBean Chip that isolates CTCs by immuno-affinity based capture. A higher number of PV CTCs were detected than from Pe. In addition, rare CTC clusters were observed in the PV blood in some cases, which were further characterized for protein expression. Gene expression analysis was performed for comparison of CTCs obtained from these two different sources. Evaluating different CTC sources along the venous drainage of a tumor could potentially offer an insight into CTC biology and spread of the disease. Citation Format: Vasudha Murlidhar, Rishindra M. Reddy, Ebrahim Azizi, Lili Zhao, Svetlana Grabauskiene, Zhuo Zhang, Nithya Ramnath, Jules Lin, Andrew C. Chang, Philip W. Carrott, William R. Lynch, Mark B. Orringer, Max S. Wicha, Nallasivam Palanisamy, David G. Beer, Sunitha Nagrath. A study of pulmonary and peripheral vein blood as sources of circulating tumor cells in early 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 1581. doi:10.1158/1538-7445.AM2015-1581
The Time Required To Achieve Complete Remission (CR) during Intensive Therapy on Total Therapy 2 Does Not Influence Event Free Survival (EFS), While Improvement in Quality of Response with Ongoing Treatment Clearly Does.
Authors: Guido Tricot, Maureen Reiner, Maurizio Zangari, Frits van Rhee, Elias Anaissie, Teresa Milner, Bart Barlogie
Journal: Blood (2005)
Six Year Follow-Up Results of a Phase II Study of Imatinib in Late Chronic Phase (L-CP) Chronic Myeloid Leukemia (CML) Post Interferon-A (IFN) Refractoriness/Intolerance.
Authors: Hagop M. Kantarjian, Charles Sawyers, Andreas Hochhaus, Charles A. Schiffer, Francois Guilhot, Dietger W. Niederwieser, Carlo Gambacorti, Richard M. Stone, Thomas Fischer, John Goldman, T. Krahnke, M. Mone, Moshe Talpaz, Brian J. Druker
Journal: Blood (2006)
Cell Scaffolds: Expanded 3D Nanofiber Scaffolds: Cell Penetration, Neovascularization, and Host Response (Adv. Healthcare Mater. 23/2016)
Authors: Jiang Jiang, Zhuoran Li, Hongjun Wang, Yue Wang, Mark A. Carlson, Matthew J. Teusink, Matthew R. MacEwan, Linxia Gu, Jingwei Xie
Journal: Advanced Healthcare Materials (2016)

On page 2993, Jingwei Xie and co-workers report a simple method to fabricate 3D expanded nanofiber scaffolds with precise control of thickness using a modified gas-foaming technique. Such expanded nanofiber scaffolds promote cellular infiltration, a regenerative response, and neovascularization after subcutaneous implantation in rats. The use of such scaffolds holds great promise in engineering tissue constructs in vitro and tissue regeneration in situ.
Outcomes of Primary Systemic Light Chain (AL) Amyloidosis in Patients Treated Upfront with Novel Agents and the Importance of Risk Adapted Treatment Strategies
Authors: Efstathios Kastritis, Maria Roussou, Maria Gavriatopoulou, Magdalini Migkou, Alexandra Gkougkoutsi, Constantinos Pamboukas, Elisavet Kaldara, Argirios Dalianis, Erasmia Psimenou, Savvas Toumanidis, Evangelos Terpos, Meletios A Dimopoulos
Journal: Blood (2012)
Phase III randomized anastrozole exercise (RAE) trial: First planned interim analysis
Authors: R. J. Macfarlane, C. Lohrisch, P. Truong, D. McKenzie, D. Jespersen, S. Nuraney, K. Gaul, K. Gelmon, H. Kennecke
Journal: Journal of Clinical Oncology (2009)

e20674 Background: Adjuvant anastrozole (aA) is associated with arthralgias/myalgias (A/M), bone density loss, and hot flushes. Analgesics offer limited relief of musculoskeletal (MSK) symptoms and are associated with side effects of their own. The benefit of exercise on bone health, muscle strength, hot flushes, and quality of life (QOL) has been demonstrated; the objective of this trial is to determine if an exercise program improves anastrozole related A/M. Methods: This is a phase III, randomized trial of standard of care (observation) vs 48 weeks (wks) of exercise for women with BC on aA. Subjects in the control group receive literature about AIs (information on bone health, management of SEs of AIs). Subjects in the intervention group participate in a semi-supervised, individualized, and graduated 3x/wk exercise program (aerobic, resistance training, stretching) for 24 wks. From wks 25–48 independent exercise is recommended 3x/wk. The 1 0 endpoint is change in MSK symptoms as measured by 12 wk SF-36v2 bodily pain scores, NCI CTG toxicity, and visual analogue scale. 2 0 endpoints are QOL, hot flushes, bone density, and body mass. Physical activity and compliance with aA was monitored in both arms. The 1 st interim analysis was planned after 10 patients were enrolled to evaluate accrual, compliance, and rate of discontinuation. Results: Accrual commenced December, 2007. Fourteen of a planned 72 patients have been enrolled (baseline data available for 13); 7 pts in the control arm (A) and 6 in the exercise arm (B). Median age was 59 (A) and 58 (B). Nine pts had baseline and 12 wk data available [5 (A), 4 (B)]. There were no withdrawals and compliance with scheduled exercise was 100%. Of the NCI CTG A/M deemed probably/definitely related to aA, there is no change in the number reported at baseline vs wk 12 in Arm A. In Arm B, 2 of 4 pts report a decrease in the number of A/M at wk 12. Mean norm-based wk 12 SF-36v2 bodily pain domain scores worsened by 4.1 in Arm A; an improvement of 1.9 in mean scores was observed in Arm B. Conclusions: Interim results show that a structured exercise program is well tolerated and compliance is high among women with aA related MSK symptoms. Early results point to a positive impact of exercise on MSK symptoms in women with early BC. Updated data will be presented. [Table: see text]
Results of a Phase II Study of Haploidentical Hematopoietic Cell Transplantation (HHCT) in Adults Using Reduced Intensity Conditioning and CD3/CD19-Depleted Grafts: Clinical Outcome and Immune Reconstitution.
Authors: Birgit Federmann, Martin Bornhauser, Lambros Kordelas, Dietrich W. Beelen, Gernot Stuhler, Rainer Schwerdtfeger, Matthias Stelljes, Gerhard Behre, Maximilian Christopeit, Christoph Faul, Wichard Vogel, Rupert Handgretinger, Lothar Kanz, Wolfgang Andreas Bethge
Journal: Blood (2009)
The High Prevalence of FLT3-ITD Mutations Is Associated with the Poor Outcome in Adult Patients with t(6;9)(p23;q34) Positive AML - Results of an International Metaanalysis.
Authors: Christian Thiede, Clara D. Bloomfield, Francesco Lo Coco, Stefan Fröhling, Wolfgang Hiddemann, Jürgen Krauter, Markus Schaich, Susan P. Whitman, Guiseppe Saglio, Konstanze Döhner, Karsten Spiekermann, Susanne Schnittger, Arnold Ganser, Gerhard Heil, Thomas Büchner, Hartmut Döhner, Richard A. Larson, Gerhard Ehninger
Journal: Blood (2007)
593. Targeted Histidinylated Lipopolyplexes for siRNA Delivery in 4T1 Mammary Carcinoma Cells
Authors: Marie-Pierre Gosselin, Cristine Gonçalves, Virginie Malard, Patrick Baril, Chantal Pichon, Patrick Midoux
Journal: Molecular Therapy (2015)

Breast cancer is the leading cause of death among women aged 35 to 50 years. siRNA-based therapies aiming at reducing the overexpression of oncogenes and genes involved in tumor progression are developed for the treatment of cancer. However, clinical applications are delayed due to the absence of very efficient and safe delivery systems. For this purpose, we develop siRNA lipopolyplexes (LPRi) which are ternary complexes between cationic liposomes comprising imidazole/imidazolium lipophosphoramidates, histidinylated-lPEI cationic polymer and siRNA (1). Compared to commercial reagents, LPRi containing anti-eGFP or anti-Luc siRNA give in vitro higher specific inhibition (80% at 50nM siRNA) of reporter gene expression in cultures of eGFP-HeLa, Luc-B16F10 and Luc-4T1 cancer cells. Transfection of the 4T1 mammary carcinoma cells line with anti-survivin siRNA induces 30% reduction in cell viability. In vivo imaging after endotracheal administration of LPRi comprising polymer or liposomes labeled with a near-infrared fluorophore indicates a sustained delivery in the lung of the formulation until 24 hours post injection. For in vivo application, PEGylated LPRi has been armed with uPA peptide or folate which binds to the urokinase receptor (uPAR) and the folate receptor (FR), respectively. These targeted LPRi exhibit a 200 nm size and a reduced positive zeta potential. When tested for their uptake efficiency in 4T1 cells, targeted LPRi show a higher endocytosis compared to untargeted LPRi. When transfected with 50nM anti-Luc siRNA formulated with LPRi containing 2% Folate or 5% uPA LPRi, a better specific inhibition (54% and 40%, respectively) of luciferase expression in Luc-4T1 cells is obtained compared to untargeted LPRi (32%). Therapeutic applications of these new targeted siRNA formulations are now tested by using the murine orthotopic 4T1 breast cancer model.