tbuckley/cabot-search huggingface dataset:
Abstract 5582: Survey of oral cancer screening participants reveals widespread misconceptions about oral cancer risk factors, independent of educational background
Authors: Cariad Chester, Jean Sabile, Grace Cho, Annie Hu, Ryoko Hamaguchi, Lauren Ellis, Jonathan S. Erdman, David Praharaj, Abhinav Golla, John Sunwoo
Journal: Cancer Research (2015)

Abstract Introduction: To develop more effective strategies to screen for oral cancer, we surveyed participants in a free oral cancer-screening event held at Stanford University to assess knowledge and understanding of oral cancer risk factors and behaviors. Method: The survey was administered by trained members of the oral cancer screening team in accordance with guidelines approved by the Stanford Research Compliance Office. Results: Participants (n = 51) were racially diverse with varied educational levels: approximately 43% of participants had completed high school only or attended some college, and 57% of participants had obtained a bachelor’s, master’s, or doctoral degree. A majority of the participants (62%) reported an annual income below $50,000, and a minority of participants (35%) had active dental insurance. Most of the participants (84%) had never previously been screened for oral cancer. All participants, regardless of educational level, demonstrated limited knowledge of the risk factors that contribute to oral cancer. Approximately 50% of the lower-education cohort and 31% of the higher-education cohort incorrectly believed that dental fillings increase the risk of developing oral cancer. Only 23% and 34% of the lower- and higher-education cohorts, respectively, correctly identified heavy alcohol consumption as a risk factor for oral cancer. Encouragingly, 85% of all participants recognized that behavioral changes can decrease one's risk of developing cancer. Conclusions: Knowledge of oral cancer risk factors was low in all participants despite the majority of responders having obtained post-secondary degrees. Our work highlights the need to expand the target audience of oral cancer educational efforts to include community members from all educational backgrounds. Note: This abstract was not presented at the meeting. Citation Format: Cariad Chester, Jean Sabile, Grace Cho, Annie Hu, Ryoko Hamaguchi, Lauren Ellis, Jonathan S. Erdman, David Praharaj, Abhinav Golla, John Sunwoo. Survey of oral cancer screening participants reveals widespread misconceptions about oral cancer risk factors, independent of educational background. [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 5582. doi:10.1158/1538-7445.AM2015-5582
Abstract 2368: Differentiated gastric cancer cells have a potential to induce cancer-associated fibroblasts
Authors: Yuncheng Li, Hiroshi Tazawa, Nishizaki Masahiko, Yuuri Hashimoto, Naoto Hori, Ryoichi Katsube, Shinji Kuroda, Kazuhiro Noma, Shunsuke Kagawa, Toshiyoshi Fujiwara
Journal: Cancer Research (2015)

Abstract Gastric cancer is one of the most common causes of cancer death. Stromal fibroblasts in the tumor microenvironment have recently been implicated in tumor growth, invasion and metastasis. Cancer-associated fibroblasts (CAFs) have been suggested to be responsible for progression of undifferentiated scirrhous gastric cancers with vast fibrous stroma. However, the relationship between differentiated gastric cancer cells and CAFs in tumor progression remains unclear. In this study, we investigated whether differentiated and/or undifferentiated human gastric cancer cells induce CAFs. We used two differentiated human gastric cancer cells (MKN-7, MKN-74) and two undifferentiated human scirrhous gastric cancer cells (KATO-III, NUGC-4). Two types of human normal fibroblasts (WI-38, FEF-3) were used for induction of CAFs. The conditioned media (CM) from all cancer cells were obtained 48 hours after serum starvation. The morphological change and expression of CAF-specific markers (α-smooth muscle actin (α-SMA), fibroblast activation protein-α (FAP)) were analyzed by microscopy and Western blot analysis, respectively, in fibroblasts treated with CM for 120 hours. Moreover, the effect of CM from CAFs in the migration ability of cancer cells was evaluated using in vitro Migration assay. The CM from differentiated MKN-7 and MKN-74 cells induced the morphological change like CAFs in normal human fibroblasts, whereas CM from undifferentiated KATO-III and NUGU-4 cells did not induce. In fact, morphologically changed fibroblasts like CAFs showed increased α-SMA expression, whereas FAP expression was not increased. The CM from morphologically changed fibroblasts, but not normal fibroblasts, significantly enhanced the migration ability of MKN-7 cells. These results suggest that differentiated gastric cancer cells have a potential to induce CAFs in the invasion process of gastric cancers. CAF-targeting therapy may be a promising antitumor strategy in differentiated gastric cancers as well as undifferentiated scirrhous gastric cancers with vast fibrous stroma. Citation Format: Yuncheng Li, Hiroshi Tazawa, Nishizaki Masahiko, Yuuri Hashimoto, Naoto Hori, Ryoichi Katsube, Shinji Kuroda, Kazuhiro Noma, Shunsuke Kagawa, Toshiyoshi Fujiwara. Differentiated gastric cancer cells have a potential to induce cancer-associated fibroblasts. [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 2368. doi:10.1158/1538-7445.AM2015-2368
Molecular Prognostic Factors and Outcome among a Cohort of Patients with Monoclonal B-Cell Lymphocytosis (MBL).
Authors: Kami Maddocks-Christianson, Curtis A. Hanson, Greg Jenkins, Clive S. Zent, Susan L. Slager, Timothy G. Call, Deborah Bowen, Renee Tschumper, Diane F. Jelinek, Neil E. Kay, Tait D. Shanafelt
Journal: Blood (2007)
354. Genetically Modified Human Mesenchymal Stromal Cell (MSC) Delivery Improved Glucose Tolerance in Diet Induced Obese (DIO) Mouse Models
Authors: Cleyton Domingues, Nabanita Kundu, Neeki Ahmadi, Sabyasachi Sen
Journal: Molecular Therapy (2016)

MSCs are undifferentiated, multipotent cells. We have previously showed that High Glucose (HG, 25mM) exposure promotes adipogenic differentiation, increased formation of ROS and decreased cellular oxygen consumption rate (OCR, using Seahorse). HG exposure also upregulated mRNA expression of adipogenic (PPARG, FABP-4, CEBP alpha and beta) and inflammatory (IL-6 and TNF alpha) genes. In this study, in order to reduce intracellular superoxide presence, we used GFP-containing Adenovirus constructs to upregulate both mitochondrial and cytosolic antioxidants (SOD2 and SOD1, respectively) and used GFP gene as a control. We showed both SOD1 and SOD2 upregulation reduced intracellular superoxide presence and improved OCR in presence of HG environment. In addition, the upregulation of IL-6 and TNFa was prevented. Next, we delivered the eGFP, SOD1 and SOD2 upregulated MSCs intra-peritoneally to DIO (60% and 45% high-fat diet fed) C57BL/6J mice. The GFP presence in constructs allowed us to track live, MSCs in-vivo. Prior to MSC delivery, all mice presented fasting blood glucose levels of 200+20 mg/dl. 60% fat fed DIO mice showed higher blood glucose levels than 45% fat fed mice. We fed 60% fat to WT mice for 6 weeks and 45% for 12 weeks. We measured blood glucose from the tail vein using a glucometer and did GTT every 2 weeks and measured body weight and imaged whole body every 3-7 days. Fat depots were harvested at 28 days. Our results indicate that MSCs did reach ("homed-in") distal fat pockets such as omental, epididymal and pericardial. Epididymal imaging was prominent with SOD1 upregulated MSCs and pericardial imaging was very prominent mice receiving SOD2 upregulated within 7 days of delivery. SOD2 upregulated MSCs showed significantly improved glucose tolerance (GTT) at 4 weeks (that is lowest area under the curve) compared to SOD1 and GFP (SOD2>SOD1>GFP) with progressive reduction in fat mass in both 60% and 45% fat fed DIO mice. We are currently processing fat depots and serum samples from MSC delivered mice, for qPCR, Western Blot and ELISA to demonstrate reduction of local and systemic inflammation. In summary, HG evokes superoxide generation, OCR reduction and adipogenic differentiation. Upregulation of superoxide dismutase, particularly mitochondrial, quenches excess of intracellular superoxide and improves MSCs respiration. Delivery of superoxide dismutase using MSCs as a gene delivery vehicle in DIO mouse model improved glucose tolerance. This is particularly important as the 45% fat DIO mouse model is particularly close to human type 2 diabetes patho-physiology. We conclude that delivery of dismutases using MSCs to the inflamed adipocyte depots may be the key to suppression of adipocyte mediated inflammation and may be a novel yet safe therapeutic tool to combat obesity associated diabetes and impaired glucose tolerance.
327. Genetic Editing for Huntington's Disease
Authors: Nicole Deglon, Cécile Meunier, Virginie Zimmer, Guillaume Perriard, Mathieu Canales, Gabriel Vachey, Lucas Hergott, Tim Beltraminelli, Thomas Dequesne, Catherine Pythoud, Maria Rey, Renaud Du Pasquier, Luc Pellerin, Anselme Perrier
Journal: Molecular Therapy (2016)

Huntington's disease (HD) is a neurodegenerative disorder caused by a pathological CAG expansion at the 3' end of the first exon of the huntingtin gene (HTT). Currently, there is no efficient treatment for HD. Editing of the mutant HTT gene with the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system represents a new and promising approach. Recognition of the HTT target sequence by a single-guide RNA sequences (sgRNA) and the Cas9 protein is inducing DNA double-strand breaks (DSB), which activate endogenous cellular repair pathways. Non-homologous end joining (NHEJ) will introduce small insertion/deletion (indel) that alter the reading frame of HTT gene while homologous directed repair (HDR) is activated in the presence of a DNA template. To validate the approach and optimize the delivery of the CRISPR system with viral vectors, we first targeted artificial sequences containing fluorescent reporter genes in HEK 293T cells. An efficient gene disruption was measured and associated with a loss of fluorescence in neurons, astrocytes, in vitro and in vivo. Furthermore, we developed multiple strategies to disrupt the mutant HTT gene. Quantification demonstrated a high rate of indels, leading to a strong reduction of HTT protein in HEK 293T cells, mouse cortical neurons and human iPS-derived neurons. Blocking HTT expression in vitro HD models is improving several physiopathological parameters. We are currently evaluating the impact of allele or non-allele specific mutant HTT editing in human neurons from HD patients. Altogether, these data demonstrate the potential of the CRISPR technology as therapeutic strategy for HD.
Macrophage Migration Inhibitory Factor (MIF) Promotes the Development of Murine Chronic Lymphocytic Leukemia (CLL)
Authors: Nina Reinart, Malgorzata Ciesla, Cornelia Rudolph, Astrid Stein, Guenter Krause, Brigitte Schlegelberger, Michael Hallek, Guenter Fingerle-Rowson
Journal: Blood (2008)
Prolonged Arterial Occlusion Caused by Thrombus Development at Sites of Arterial Bifurcation
Authors: Haruo Araki, Noriyuki Ishihara
Journal: Circulation (1997)

Although thrombogenic atheromas frequently develop at sites of arterial branching or bifurcation, the nature of such thrombus formation remains unclear. In this study, small rat mesenteric arteries (about 0.3 mm id) were observed using a video-microscope system. Exposure of the media by inducing compression damage over a short segment caused occlusive thrombus formation and subsequent spontaneous reperfusion repeatedly over about 30 min. Compression damage was induced either at a site just distal to the bifurcation (group 1, n = 7) or 5-10 mm downstream from the bifurcation (group 2, n = 7). The number of thrombotic occlusions was similar in the 2 groups, but the total duration of occlusion was significantly higher in group 1 (540 +/- 47 sec) than in group 2 (295 +/- 24 sec) (p < 0.01). The total duration of occlusion in group 1 was significantly reduced to 273 +/- 16 sec (p < 0.01) by mechanical interruption of flow in the other, intact, arterial branch. In the presence of blood flow through the intact branch, the occlusive thrombus at the bifurcation further enlarged in the direction of the intact branch, resulting in a significantly larger thrombus than in the absence of blood flow (17.1 +/- 2.1 vs 9.2 +/- 0.9 x 10(-2) mm2, p < 0.01). Stasis of the arterial blood per se did not affect the duration of thrombotic occlusion or increase plasma fibrinolytic activity. Thus, arterial occlusion caused by a thrombus arising at arterial bifurcations may be prolonged because of enlargement of the thrombus owing to the action of platelets in blood flowing through the intact branch.
Modified Topotecan Combination with Cyclophosphamide and Ara-C (CAT) for Patients with Refractory/Relapsed Leukemia.
Authors: Sui-jing Wu, Xin Du, Wei Lin, Zi-lun Huang, Xiao-li Zhou, Jian-yu Weng, Li-ye Zhong, Ze-sheng Lu
Journal: Blood (2007)
146. Optimizing Safety and Long-Term Efficacy of Liver Gene Therapy With Non-Integrating Naked-DNA Minicircle Vectors Expressing Their Transgene from a Natural Promoter
Authors: Hiu Man Viecelli, Andrea Schlegel, Tanja Scherer, Martin Schleef, Cary O. Harding, Beat Thöny
Journal: Molecular Therapy (2015)

We have reported successful therapy of phenylketonuria (PKU) in the mouse model C57Bl/6-Pahenu2 by using naked DNA vectors, so called minicircles (MCs) which are devoid of any viral or bacterial sequences, upon liver-directed phenylalanine hydroxylase (Pah) gene transfer via hydrodynamic tail vein injection (Viecelli et al., Hepatology 2014). To further address the biosafety of these non-integrating vectors for gene therapy, we performed partial hepatectomy to investigate the episomal state of MCs. MC-treated PKU mice were challenged by resecting as much as 70% of the liver, and blood L-Phe levels were followed upon regeneration of the two remaining liver lobes. We found a re-rise of blood L-Phe values back to pre-treatment levels as well as the loss of Pah-transgene expression, indicating that treated PKU mice had lost therapeutic MC vectors during liver regeneration. These results corroborate our previous (but also others) observations that MC-DNA do not integrate – or only at a very low frequency that cannot be detected by our assays – and thus express their transgene predominantly as episomal vectors. We then further optimized the expression cassette to improve transgene expression which may allow efficacy at lower vector doses. Our results showed that the therapeutic doses of MCs could be significantly lowered by using a codon-optimized murine Pah (mPah) cDNA in combination with a truncated 5'-intron (IVS1B). Moreover, when using the natural or endogenous 3.6 kb murine Pah-promoter to drive the Pah transgene, vector doses could again be significantly lowered compared to two other liver-specific promoters, the synthetic P3 hybrid enhancer/promoter or the classical CBA (modified cytomegalovirus enhancer/chicken β-actin) promoter. In conclusion, MC-vectors which do not have a defined size-limitation, offer a favorable safety profile and have the potential for long-term gene-therapy of liver defects.
PTH-084 Gluten-free diet adherent: but at what cost?: Abstract PTH-084
Authors: S M Barratt, J S Leeds, S Lin, H Wilson, D S Sanders
Journal: Gut (2010)

<h3>Introduction</h3> A gluten-free diet (GFD) is the mainstay of treatment in Coeliac Disease. The impact of this restrictive diet on the quality of life (QoL) of the Coeliac individual is uncertain and debated. These uncertainties may stem from focusing on the level of dietary adherence rather than the difficulties faced to achieve adherence. We hypothesised that the more difficult the individual perceives following a GFD, the lower their QoL will be as a result. <h3>Methods</h3> Postal survey (n=573) of histologically proven Coeliac individuals (n=225) and non-health seeking age and sex matched controls (n=348). Questionnaire included the MOS Short-Form 36-Item (SF-36) QoL measure, The Hospital Anxiety and Depression Scale (HADS) and an assessment of GFD adherence, lifestyle obstacles encountered following the diet and perceived degree of difficulty following a GFD. <h3>Results</h3> Around two-thirds of the Coeliac group reported full GFD adherence (always: 64.6%; mostly: 24.8%; sometimes: 6.6% and rarely/never: 4%). Very little difference was observed in SF-36 or HADS scores when comparing “always” adherent individuals to partial/none adherent (p=ns). Many reported lifestyle obstacles following the diet: eating out (88%), at work (27%), at home (12%), travelling (73%), personal relationships (13%) and socialising (71%). Despite the level of GFD adherence most Coeliac individuals reported difficulty with the GFD: no difficulty (20%), difficult sometimes (61%), difficult mostly (14%) and impossible (5%). Stepwise reductions in QoL were observed in the Coeliac group based on the increasing level of GFD difficulty reported. Mental/psychological aspects of QoL were particularly reduced (p=&lt;0.0001). 9Mostly difficult9 was associated with possible anxiety and probable depression based on median HADS scores (p=&lt;0.0001) (Abstract 084). <h3>Conclusion</h3> Comparing our Coeliac group based on adherence level alone would have revealed very little difference in QoL suggesting the GFD has a negligible impact on patient wellbeing. However, group comparison based on difficulty level reveals significant differences and a high likelihood of anxiety and depression associated with the highest degrees of difficulty. We contend that future research must consider adherence in the context of difficulty if a more informed appreciation of the impact this diet has on Coeliac individuals is to be achieved.
34. Stromal Vascular Fraction as a Novel Stem Cell-Based Therapy for a Mouse Model of Multiple Sclerosis
Authors: Annie C. Bowles, Amy L. Strong, Rachel M. Wise, Robert C. Thomas, Brittany Y. Gerstein, Rebecca S. Lipschutz, Jeffrey M. Gimble, Bruce A. Bunnell
Journal: Molecular Therapy (2015)

Multiple sclerosis (MS) is the most common neurodegenerative disorder affecting young adults worldwide and remains an unmet clinical challenge. MS is caused by an autoimmune reaction against constituents of the central nervous system (CNS). Subsequent immune cell infiltration into CNS tissues lead to widespread inflammation, demyelination, and pathological lesions causing debilities such as tremors, fatigue, and progressive loss of motor functions. These pathological hallmarks are reproducible in the mouse experimental autoimmune encephalomyelitis (EAE) model of MS. Several clinical trials have demonstrated the safety and efficacy of adipose-derived stem cell (ASC)-based therapies in treating various disorders. ASC-based therapies are considered favorable due to their abundance in adult human adipose depots, less invasive harvest protocol, and potent immune-modulatory capabilities. However, due to the requisite for ex vivo culture isolation and expansion, alternative therapies are necessary. As such, the stromal vascular fraction (SVF) of adipose tissue has been considered a potential alternative to ASC-based therapies. The SVF consists of ASCs, adipocytes, and numerous leukocytes. The combination of cell types is believed to provide enhanced effectiveness by reducing inflammation and repairing damage. Currently, the SVF has advanced to clinical trials as a promising therapy for various medical indications including neurodegenerative diseases. Nevertheless, the efficacy of SVF therapy for MS patients or EAE mice has not been investigated. In this study, 1×106 SVF cells or ASCs were administered by intraperitoneal injected into EAE mice during the progression of disease, i.e. early, mid-stage, and chronic phases. Immune-modulatory activities of injected SVF and ASCs were analyzed using flow cytometry and qRT-PCR of lymphoid and CNS tissues and blood at the endpoint of the study. Both SVF and ASC treatments reduced pathological infiltrates and levels of inflammatory cytokines. Results show greater efficacy for reducing disease severity, recovery of motor functions, and improvement in histological examinations from EAE mice injected with SVF than ASCs, regardless of the timing. Together, SVF cells are more comprehensive at treating the immunopathogenesis of EAE by producing robust immune-modulatory effects. The translational aspects of this study support the use of SVF over ASCs as a prospective therapy for MS due to these promising results.
Abstract A2-31: Chemical proteomics approach reveals a monoacylglycerol lipase-dependent migration suppression of melanoma cells by andrographolide
Authors: Ya-Hsin Hsu, Ting-Yun Huang, Lee-Chiang Lo, Shu-Ling Fu, Chao-Hsiung Lin
Journal: Cancer Research (2015)

Abstract Andrographolide is the major chemical component of an herbal plant, Andrographis paniculata, and has been reported to exhibit anti-cancer activity. We had previously demonstrated that andrographolide can suppress the migration and invasion of a highly metastatic melanoma cell, B16F10, but the molecular target and regulatory mechanism underlying this phenomenon remain unknown. A chemical proteomics approach using serine hydrolase activity probes and mass spectrometry-based identification was carried out to reveal that monoacylglycerol lipase (MAGL) of lipid metabolism is involved in the andrographolide-mediated suppression of B16F10 cell migration. MAGL has been reported to be elevated in aggressive cancers and associated with tumor metastasis. We observed that the hydrolase activity of MAGL in B16F10 cells was decreased upon andrographolide treatment but not in the poorly metastatic B16F1 cells. In addition, a known MAGL-specific inhibitor (JZL184) was used to demonstrate that suppression of MAGL enzyme activity could reduce B16F10 migration. Notably, overexpression of MAGL in B16F10 cells abrogated the andrographolide-mediated suppression of B16F10 migration, but such overexpression could not rescue the JZL184-mediated suppression. Further analysis showed a downregulation of MAGL mRNA levels in B16F10 cells upon treatment of andrographolide. With the use of an IKK inhibitor (Bay11-7082), the NF-kB signaling pathway is shown to be involved in the andrographolide-mediated suppression of MAGL expression. Taken together, we herein demonstrate that andrographolide suppresses melanoma cell migration via transcriptional downregulation of monoacylglycerol lipase, providing a new anti-cancer mechanism of andrographolide and a basis for further development of potent derivatives. Citation Format: Ya-Hsin Hsu, Ting-Yun Huang, Lee-Chiang Lo, Shu-Ling Fu, Chao-Hsiung Lin. Chemical proteomics approach reveals a monoacylglycerol lipase-dependent migration suppression of melanoma cells by andrographolide. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-31.
Secondary Bortezomib-Resistance Is Characterized by Upregulation of Proteasomal Subunits and Their Insufficient Inhibition by Bortezomib, Which Can Be Overcome by Alternative Proteasome Inhibitors Combined with Induction of the ER Stress Response.
Authors: Thomas Ruckrich, Jeannette Gogel, Marianne Kraus, Huib Ovaa, Christoph Driessen
Journal: Blood (2006)
Effects of Pathogen Inactivation Using Amotosalen-UVA on Coagulation Parameters in Apheresis and Whole Blood Derived Frozen Plasma in a Large Blood Bank Setting.
Authors: Markus M. Mueller, Hans-Ulrich Pfeiffer, Margaret Rheinschmidt, Bernd Poetzsch, Johannes Oldenburg, Laurence Corash, Erhard Seifried, Reinhard Henschler
Journal: Blood (2006)