tbuckley/cabot-search huggingface dataset:
432. Valproic Acid Treatment Enhances Hematopoietic Stem and Progenitor Cell Multipotency Ex Vivo for Enhanced Long-Term Engraftment of Gene-Modified Cells
Authors: Anthony Conway, Alisa Boyko, Jeremy Hardin, Michael C. Holmes, Gregory J. Cost
Journal: Molecular Therapy (2016)

The promising field of genome editing in hematopoietic stem and progenitor (HSPC) for use in autologous and allogeneic transplantation therapies relies on being able to engraft the edited cells into the bone marrow and to have those engrafted cells produce all the hematopoietic lineages necessary for proper immune and red blood cell function. Depending on the cell source to be used in the editing process, the fraction of CD34+ HSPCs can be quite low - approximately 0.0005%, 0.01%, or 0.1% for mobilized peripheral blood (mPB), bone marrow aspirate (BM), or cord blood, respectively. The fraction of long-term repopulating true stem cells (LT-HSCs) within these CD34+ cell populations, capable of long-term reconstitution of the entire hematopoietic lineage after transplantation, is even lower (<1%). In addition, it has recently been shown that LT-HSCs derived from cord blood can be much less permissive to homology-directed repair (HDR)-driven gene correction which may be essential for some types of therapeutic genome editing. Several groups have discovered small molecules that promote expansion of cord blood-derived CD34+ HSPCs ex vivo while maintaining the stemness of the HSPCs, however these effects have not been reported in HSPCs from mPB or BM. Here we show that the small-molecule epigenetic modifier valproic acid (VPA) improves HDR-mediated targeted integration (TI) in mPB and BM HSPCs. In addition to increasing the fraction of LT-HSCs with TI by up to 100-fold, VPA also dramatically increases the overall number of cells expressing LT-HSC markers (CD34+CD133+CD90+CD49f+ or CD34+CD38-CD45RA-CD90+CD49f+) by up to 500-fold. VPA-treated gene-edited HSCs differentiate normally in vitro and retain consistent levels of TI in both erythroid and myeloid lineages. These results further the development of genome-edited mPB and BM-derived HSPC therapies.
Initial Screening Transferrin Saturations, Serum Ferritin Concentrations, and HFE Genotypes in Whites and Blacks in the Hemochromatosis and Iron Overload Screening (HEIRS) Study.
Authors: James C. Barton, Ronald T. Acton, Fitzroy W. Dawkins, Paul C. Adams, Laura Lovato, Cathy Leiendecker-Foster, Christine E. McLaren, David M. Reboussin, Mark R. Speechley, Victor R. Gordeuk, Gordon D. McLaren, Phyliss Sholinsky, Emily L. Harris
Journal: Blood (2004)
Comparison of Blood Graft Cellular Content in Myeloma (MM) Patients and Non-Hodgkin Lymphoma (NHL) Patients Mobilized with Chemotherapy Plus G-CSF with or without Plerixafor
Authors: Esa Jantunen, Ville Varmavuo, Raija Silvennoinen, Piia Valonen, Taru Kuittinen, Tapio Nousiainen, Pentti Mäntymaa
Journal: Blood (2012)
Abstract 1159: Ketosis and hyperbaric oxygen elicit potent anti-cancer effects in vitro and in vivo
Authors: Angela Poff, Nathan Ward, Thomas Seyfried, Dominic D'Agostino
Journal: Cancer Research (2015)

Abstract The Warburg effect and tumor hypoxia underlie a unique cancer metabolism characterized by glucose dependency and abnormal mitochondrial function. We have previously shown that this phenotype can be exploited therapeutically by glucose restriction with the ketogenic diet, dietary ketone supplementation, or hyperbaric oxygen (HBOT). We hypothesized that combining these therapies would be an effective non-toxic treatment regimen, so we tested this combination therapy in the VM-M3 mouse model of metastatic cancer. Treated mice exhibited decreased tumor growth rate, decreased metastatic spread to the lungs, kidneys, spleen, adipose, and liver, decreased liver tumor vascularization, and lived twice as long as controls. To further characterize the effects of these therapies, we measured proliferation, viability, ROS production, and expression of key signaling molecules in VM-M3 cells exposed to the following conditions: high glucose (control; 25mM), low glucose (LG; 3mM), ketone supplementation (βHB; 5mM), hyperbaric oxygen (HBOT; 90 min, 2.5 ATA), or combination therapy (LG+BHB+HBOT). Proliferation of VM-M3 cells was measured with trypan blue hemocytometry and was significantly decreased from controls at 24, 48, 72, and 96 hours. Viability of VM-M3 cells was measured by fluorescence microscopy with calcein and EthD-1 and was decreased by 19.2% in LG, 12.5% in βHB, and 38.2% in LG+βHB+HBOT treated cells compared to control. ROS (superoxide) production was measured by fluorescent microscopy with DHE and was increased by 46% in HBOT and by 48% in LG+βHB+HBOT treated cells. Treatment with βHB significantly decreased expression of HIF-1α and pAkt compared to control as measured with western blot. HBOT also inhibited HIF-1α expression but increased pAkt expression in vitro. This study strongly supports further investigation into mechanisms of action and the use of these metabolic therapies as a potential cancer treatment. Citation Format: Angela Poff, Nathan Ward, Thomas Seyfried, Dominic D'Agostino. Ketosis and hyperbaric oxygen elicit potent anti-cancer effects in vitro and in vivo. [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 1159. doi:10.1158/1538-7445.AM2015-1159
PTU-019 Nasal or standard endoscopy (nose) for diagnosis of Barrett's oesophagus – efficacy and patient tolerance: Abstract PTU-019
Authors: K M Shariff, E L Bird-Lieberman, M O'Donovan, Z Abdullahi, S L Vowler, J Blazeby, R C Fitzgerald
Journal: Gut (2010)

<h3>Introduction</h3> In order to detect all cases of Barrett9s oesophagus (BE) in the population, with the aim of reducing adenocarcinoma associated mortality, screening needs to be considered. Unsedated transnasal endoscopy (TNE) can potentially offer a safer and less expensive alternative to conventional sedated endoscopy (CE) for detecting BE. <h3>Aims</h3> (1) To evaluate the sensitivity and specificity of TNE in diagnosing BE compared with CE. (2) To assess patient acceptability of TNE for a future multicentre screening trial. <h3>Methods</h3> Patients with known BE under surveillance and those referred for routine endoscopy for other reasons underwent both TNE and CE in a randomised cross-over design. TNE findings of endoscopic BE, biopsy size and presence of intestinal metaplasia (IM) were compared against CE, which was used as gold standard. Pre and post endoscopy short-form spielberger state-trait questionnaires (SF6), a visual analogue scale and a single question addressing preference for endoscopy type were used to measure patient acceptability of the procedures. <h3>Results</h3> Of 57 patients randomised, 50 completed the study. All 22 BE cases with columnar lined epithelium (CLE) on CE were correctly diagnosed by TNE. Although the biopsy size of TNE was significantly smaller compared to CE (mean size 2.59 vs 4.74 p&lt;0.0001), it detected an equal number of IM cases and there was one case of low grade dysplasia which interestingly was not picked up by CE. Abstract 019 shows sensitivity, specificity and diagnostic accuracy (including Pearson-Clopper CI) for diagnosing BE and IM using TNE compared with CE as the gold standard. The mean difference between the two procedures in determining the length of BE was 0.02. The 95% Bland and Altman limits of agreement was between −2.08 and 2.13 with 49 cases (98%) falling within the pre-determined level of agreement of ±1.5 cm. The mean pre and post procedure anxiety score for TNE (13.3 vs 14.0) and CE (13.2 vs 13.5) were not significantly different (p=0.15). The post endoscopy experience of TNE was comparable to CE (mean 5.0 vs 4.9, p=0.77). <h3>Conclusion</h3> TNE is accurate in diagnosing BE and detecting IM. Despite the smaller biopsy size, it detected an equal number of IM cases and showed potential to detect dysplasia. It was well tolerated and preferred by patients and may be an efficient screening method for BE.
Abstract 2426: JAK inhibitors as new drugs for treatment of paclitaxel-resistant anaplastic thyroid cancer
Authors: Tomoyuki Fujita, Takayuki Sasaki, Zheng Wang, Kayoko Koshikawa, Hajime Nishimura, Minoru Fujimori
Journal: Cancer Research (2015)

Abstract Background: Anaplastic thyroid carcinoma (ATC) is a rare but particularly aggressive solid tumor that has a poor prognosis, despite multimodal treatment approaches. New chemotherapy agents are being developed and taxanes have efficacy against ATC. Targeted agents including fosbretabulin, imatinib, erlotinib and gefitinib have also been examined, but were unsuccessful. These results suggest that innovative strategies are required for treatment of ATC. Therefore, our primary aim was to determine the genes and pathways related to sensitivity to paclitaxel as biomarkers in ATC. Our secondary aim was to identify new genes and pathways as therapeutic targets in ATC. Materials and Methods: We analyzed differences in gene expression profiles before and after treatment with paclitaxel in two ATC cell lines: KTA-3 cells, which are sensitive to paclitaxel, and TTA-2 cells, which are resistant to paclitaxel. Parametric Analysis of Gene Set Enrichment (PAGE) using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Transcriptional Regulatory Element Database (TRED) were performed to detect significant differences at the level of functional categories such as pathway genes and transcriptionally regulated genes. Results: Genes in the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway (KEGG classification) were downregulated significantly in KTA-3 cells compared with TTA-2 cells after treatment with paclitaxel. PAGE showed that breast cancer susceptibility gene (BRCA)1-related genes including Janus kinase (JAK)1, JAK2 and signal transducer and activator of transcription (STAT)3 were downregulated most significantly in KTA-3 cells compared with TTA-2 cells after paclitaxel treatment. Several JAK inhibitors inhibited cell growth in paclitaxel-resistant ATC cells. Conclusions: JAK-STAT pathway may be a biomarker of paclitaxel sensitivity in ATC and may represent a new target in drug development for ATC therapy. Citation Format: Tomoyuki Fujita, Takayuki Sasaki, Zheng Wang, Kayoko Koshikawa, Hajime Nishimura, Minoru Fujimori. JAK inhibitors as new drugs for treatment of paclitaxel-resistant anaplastic thyroid 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 2426. doi:10.1158/1538-7445.AM2015-2426
Abstract 4560: Targeting chronic lymphocytic leukemia with p53 deficiency with phenethyl isothiocyanate
Authors: Jinyun Liu, Gang Chen, Helen Pelicano
Journal: Cancer Research (2015)

Abstract Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the United States and Europe. Despite recent advance in new therapeutic agents that have improved treatment outcomes, CLL remains incurable. CLL patients with loss of p53 due to unfavorable cytogenetic alterations such as chromosome 17p deletion often exhibit more malignant disease phenotype, are resistant to many standard therapeutic agents, and have poor clinical outcomes. Thus, finding effective treatment for CLL with p53 deficiency represents a significant challenge, and development new agents and therapeutic strategies to effectively kill CLL cells with loss of p53 function would have profound clinical implications in CLL treatment. We have recently created a mouse model with Tcl1-Tg:p53-/- genotype that resembles the aggressive human CLL disease with p53 deficiency (17p-deletion). We showed that leukemia cells isolated from this mouse model as well as primary human leukemia cells with 17p deletion isolated from CLL patients are resistant to standard anti-CLL agents. Because p53 plays important roles in regulation of apoptosis and in maintaining mitochondrial function/normal metabolism/redox homeostasis, we hypothesized that a loss of p53 function in CLL with 17p- or p53 mutations would on one hand lead to drug resistance and poor therapeutic response to conventional treatment, and would on the other hand also cause mitochondrial dysfunction and high ROS stress. Our study tested the possibility to use the high oxidative stress as a biochemical basis to effectively target the drug-resistant CLL cells with p53 deletion using redox-modulating strategy in vitro and in vivo. Our results showed that ROS-mediating strategies could overcome drug resistance of CLL cells with p53 deficiency, and was able to effectively eliminate fludarabine-resistant CLL cells using phenethyl isothiocyanate (PEITC), which induced rapid glutathione depletion and caused severe ROS accumulation leading to massive death of CLL cells in culture. Importantly, PEITC also exhibited promising in vivo therapeutic activity in the CLL mouse model as a single agent, leading to a significant prolongation of the mouse survival time. Since PEITC is a natural compound found in vegetables with very low toxicity to normal cells, the results of this study may have important therapeutic implications. Our study suggests that PEITC may potentially be used for clinical treatment of CLL with 17p deletion and improve the outcome of this subpopulation of CLL patients, who would otherwise refractory to standard therapeutics. Citation Format: Jinyun Liu, Gang Chen, Helen Pelicano. Targeting chronic lymphocytic leukemia with p53 deficiency with phenethyl isothiocyanate. [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 4560. doi:10.1158/1538-7445.AM2015-4560
Abstract 1503: HP1-gamma's expression correlates with glioma grade and survival and is a putative marker of glioma stem like cells
Authors: Uros Rajcevic, Sabrina Fritah, Petr V. Nazarov, Mara Popovic, Rajko Kavalar, Tadej Strojnik, Neza Podergajs, Jaco C. Knol, Thang V. Pham, Sander R. Piersma, Connie R. Jimenez, Simone P. Niclou
Journal: Cancer Research (2015)

Abstract Genetic and signaling pathways involved in the development of glioblastoma have been relatively well characterized. Gene/protein expression profiles of glioblastoma have been described that reflect stem-like phenotype of the tumor. However, no reliable individual markers exist up-to-date that differentiate glioblastoma stem-like cells from the neural stem cells. Glioblastoma appears to be of heterogenous cellular population, but detailed cellular origin of these tumors is unknown. Using a label-free proteomic approach, we analyzed two different glioma models with proven de novo tumorigenic properties, and compared them with primary neurospheres. Of almost 2000 identified proteins, we found 482 to be significantly differentially expressed among the three groups. Among the identified substrates, the clusters of proteins with highest density of protein-protein interactions were functionally enriched in RNA processing related to development and metabolic processes. We then focused on two putative quantitative markers of glioma stem-like cells, HP1-gamma (Heterochromatin Protein 1- gamma) - CBX3 (chrome box 3), an epigenetic regulator involved in RNA processing, and LDHA (Lactate Dehydrogenase A), a key metabolic enzyme of anaerobic glycolysis. We quantitated their expression in glioma tissue of different grades in a large set of patient samples and were able to show that the expression of HP1-gamma, highly upregulated in glioblastoma stem-like cells, correlates to glioma grade. Independent analysis of publicly available glioma patient data showed that LDHA expression is linked to IDH1 mutation status both in high grade and low grade gliomas. The same analysis reinforced our findings towards an increased involvement of CBX3/HP1-gamma in high grade gliomas. Altogether, CBX3/HP1-gamma and LDHA are novel biomarkers for cancer stem cell phenotype with different clinical importance in gliomas. Citation Format: Uros Rajcevic, Sabrina Fritah, Petr V. Nazarov, Mara Popovic, Rajko Kavalar, Tadej Strojnik, Neza Podergajs, Jaco C. Knol, Thang V. Pham, Sander R. Piersma, Connie R. Jimenez, Simone P. Niclou. HP1-gamma's expression correlates with glioma grade and survival and is a putative marker of glioma stem like 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 1503. doi:10.1158/1538-7445.AM2015-1503
The Comparison of Myeloablative Versus Reduced Intensity Conditioning Regimen in ABO Mismatched Allogeneic Hematopoietic Cell Transplantation.
Authors: Pervin Topcuoglu, Mutlu Arat, Tugce Bolukbasi, Ender Soydan, Yesim Ozer, Muhit Ozcan, Gunhan Gurman, Taner Demirer, Hamdi Akan, Meral Beksac, Onder Arslan, Osman Ilhan
Journal: Blood (2004)
NLRP6 in Host Target Tissues Exacerbates Graft-Versus-Host Disease
Authors: Tomomi Toubai, Corinne Rossi, Hiroya Tamaki, Nathan Mathewson, Katherine Oravecz-Wilson, Cynthia Zajac, Chen Liu, Stuart Brabbs, Yaping Sun, Grace Chen, Pavan Reddy
Journal: Blood (2015)
Analysis of Immunoglobulin Heavy Chain Variable Genes In Burkitt Lymphoma Uncovers An Antigen Role In the Pathogenesis of the Disease
Authors: Maria Joao Baptista, Marta Crespo, Eva Calpe, Carles Codony, Eva Fernandez, Lluis Colomo, Teresa Marta Cardesa-Salzmann, Pau Abrisqueta, Francesc Bosch
Journal: Blood (2010)
Similar Survival after Umbilical Cord Blood (UCB) and HLA-Matched Adult Donor Transplantation By Disease Risk Index (DRI) Assignment
Authors: Nelli Bejanyan, Claudio G Brunstein, Qing Cao, Aleksandr Lazaryan, Erica D. Warlick, Celalettin Ustun, Shernan G. Holtan, Mukta Arora, Veronika Bachanova, Michael R. Verneris, John E. Wagner, Daniel J. Weisdorf
Journal: Blood (2015)
An oesophageal and pulmonary association not to forget
Authors: Bernie Young Sunwoo
Journal: Thorax (2016)

A 45-year-old Indian man with a history of achalasia presented with fevers, cough and fatigue.He had undergone endoscopic dilatation for achalasia several years prior.Chest radiograph revealed a dilated oesophagus and a left perihilar opacity (figure 1).He was treated for community-acquired pneumonia with a course of clarithromycin but had persistent cough, fatigue and weight loss with nonresolving radiographic infiltrates.A 3-week course of amoxicillin clavulanate was prescribed for suspected aspiration with little clinical improvement, and a chest CT was performed (figure 2).The patient had never smoked and had moved to the USA from India over 20 years ago, last travelling to India 1 year prior.Prior purified protein derivative skin tests (PPDs) were negative.HIV testing was negative.Induced sputums isolated Mycobacterium fortuitum.Bronchoscopy was performed showing no endobronchial lesions.Bronchoalveolar lavage from the left lower lobe also grew M. fortuitum.Mycobacterium tuberculosis PCR and all other cultures were negative.Cytology was negative.M. fortuitum is a rapidly growing nontuberculous mycobacterium that is ubiquitous in the environment.It has been associated with infections of the skin, soft tissue, wounds and bone.Pulmonary infection is uncommon in the immunocompetent host with no underlying lung disease except in the setting of gastro-oesophageal
PTH-011 Missing colorectal cancer: the muddle of haemoglobin, ferritin and mcv
Authors: J A McCaughan, I Hoeritzauer, P Lynch, A Varghese
Journal: Gut (2010)

<h3>Introduction</h3> The development of iron deficiency anaemia is well recognised as an early presentation of colorectal cancer. The World Health Organisation defines anaemia as a haemoglobin of &lt;13 g/dl in men and 12 g/dl in women. The presence of a low ferritin is the most powerful test for iron deficiency with a ferritin of &lt;50 μg/l consistent with this diagnosis. Recent literature suggests that a lower limit of 100 μg/l is more sensitive when considering a diagnosis of colorectal cancer. In iron deficiency anaemia, red cells classically have a low mean cell volume (MCV). The aims of this study are fourfold: To evaluate the change in haemoglobin in the 2 years prior to colorectal cancer diagnosis To gauge the adequacy of investigation of anaemia To assess the correlation between ferritin and colorectal cancer in anaemic patients To explore the relationship between MCV and low ferritin <h3>Methods</h3> The records of 194 patients diagnosed with colorectal cancer between April 2007 and September 2009 were reviewed retrospectively. Haemoglobin, ferritin and MCV within the previous 2 years were recorded. <h3>Results</h3> 186 patients had a previous haemoglobin available. 76 patients (41%) were anaemic prior to diagnosis and a further 25 (13%) had a 10% drop in haemoglobin from baseline. 18% of these patients had a low MCV. No patients had an elevated MCV. Of the 101 patients with anaemia or a 10% haemoglobin drop, 37 (37%) had iron studies performed. Ferritin was &lt;50 μg/l in 73% of cases and &lt;100 μg/l in 97%. A normal MCV was found in 64% of patients with a ferritin of &lt;100 μg/l. The median time from presentation of anaemia to diagnosis of colorectal cancer was 3 months but 24 patients had a delay of between 12 and 24 months. The median time to diagnosis was the same for patients with a low ferritin or a 10% drop in haemoglobin. <h3>Conclusion</h3> In the 2 years preceding colorectal cancer diagnosis, 41% of patients develop anaemia and a further 13% have a 10% drop in haemoglobin. This remains poorly investigated. A normal MCV is falsely reassuring and patients meeting developing anaemia or a 10% drop in haemoglobin should have iron studies performed. This study confirms recent findings that a lower limit for ferritin of 100 mcg/l is more sensitive when considering colorectal cancer. 24% of patients wait 12–24 months between the development of anaemia or a 10% drop in haemoglobin and a diagnosis of colorectal cancer. This percentage could be significantly reduced by the timely investigation of these patients with iron studies. Referral for urgent GI investigations should be made for patients with a ferritin &lt;100 μg/l and no overt blood loss from another source.
Methodologic Variations in the Determinations of Anti-Platelet Factor 4-Heparin Antibodies in Patients Suspected of Having Heparin Induced Thrombocytopenia: Diagnostic and Prognostic Implications.
Authors: Jawed Fareed, Margaret Prechel, Michelle Kujawski, He Zhu, Jeanine Walenga, Debra Hoppensteadt, Josephine Cunanan, Renu Saxena
Journal: Blood (2007)
Allogeneic Stem Cell Transplantation (SCT) Using Rabbit-ATG (Thymoglobulin®) and 2-Gy Total Body Irradiation (TBI): Reliable Early Engraftment with Minimal Acute Graft Vs. Host Disease (AGVHD).
Authors: Amir A. Toor, Tulio Rodriguez, Najeeb Mohideen, Mala Parthasarathy, Patrick J. Stiff
Journal: Blood (2004)