tbuckley/cabot-search huggingface dataset:
Abstract 2213: Evaluation of bias associated with high-multiplex, target-specific pre-amplification
Authors: Steven T. Okino, Michelle Kong, Yan T. Wang
Journal: Cancer Research (2015)

Abstract We developed a novel PCR-based pre-amplification (PreAmp) technology that can increase the abundance of over 350 target genes one million-fold. To assess potential bias introduced by PreAmp we utilized ERCC RNA reference standards, a model system that quantifies measurement error in RNA analysis. We assessed three types of bias: amplification bias, dynamic range bias and fold-change bias. We show that our PreAmp workflow does not introduce significant amplification and fold-change bias under stringent conditions. We do detect dynamic range bias if a target gene is highly abundant and PreAmp occurred for 16 or more PCR cycles; however, this type of bias is correctable. To validate PreAmp performance in an actual gene expression profiling experiment, we analyzed a panel of genes that are regulated during differentiation using the NTera2 stem cell model system. We find that results generated using PreAmp are statistically equivalent to results obtained using standard qPCR without the pre-amplification step. Importantly, PreAmp maintains patterns of gene expression changes across samples; the same biological insights would be derived from a PreAmp experiment as with a standard gene expression profiling experiment. Our PreAmp technology can facilitate accurate analysis of extremely limited samples in gene expression profiling experiments. Citation Format: Steven T. Okino, Michelle Kong, Yan T. Wang. Evaluation of bias associated with high-multiplex, target-specific pre-amplification. [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 2213. doi:10.1158/1538-7445.AM2015-2213
Abstract SY15-04: Angiogenesis revisited: Endothelial cell metabolism as a target
Authors: Peter Carmeliet
Journal: Cancer Research (2015)

Abstract Angiogenesis, the growth of new blood vessels, plays a crucial role in numerous diseases, including cancer. Anti-angiogenesis therapies have been developed to starve cancer cells from nutrients. Clinically approved anti-angiogenic drugs prolong the survival of cancer patients, but their success is limited by intrinsic refractoriness and acquired resistance. New strategies are thus needed to block tumor angiogenesis via alternative mechanisms. We recently reported that PFKFB3-driven glycolysis regulates the endothelial cell function and identity during vessel sprouting, even capable of overruling the potent activity of Notch, and that its loss in endothelial cells causes vascular hypobranching defects. Moreover, partial and transient reduction of glycolysis by blocking PFKFB3 reduced pathological angiogenesis in several disease models. Ongoing studies explore the role of lipid and amino acid metabolism in vessel sprouting, and assess the therapeutic potential of targeting these metabolic pathways for anti-angiogenic therapy. Citation Format: Peter Carmeliet. Angiogenesis revisited: Endothelial cell metabolism as a target. [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 SY15-04. doi:10.1158/1538-7445.AM2015-SY15-04
Abstract AS06: Development and characterization of an oviduct-specific model of high-grade serous carcinoma
Authors: Yali Zhai, Rong Wu, Tom C. Hu, Eric R. Fearon, Kathleen R. Cho
Journal: Clinical Cancer Research (2015)

Abstract Recent studies suggest the most common and lethal type of “ovarian” cancer, high-grade serous carcinoma (HGSC), often arises from fallopian tube epithelium rather than the ovarian surface epithelium. Their intraperitoneal location and microscopic size make it very difficult to screen for, or study the biology of early tubal lesions in humans, as most are discovered incidentally in women with hereditary predisposition to ovarian cancer who elect prophylactic salpingo-oophorectomy for cancer risk-reduction. Although most cases of pelvic HGSC probably originate in the fallopian tube, roughly one-third lack evidence of tubal origin. These cases may arise from ectopic tubal-type epithelium (endosalpingiosis) present in the ovary, peritoneum, or at other sites. Mouse models that closely mimic the genetics and biology of human HGSCs may be useful for clarifying how tubal and non-tubal pelvic HGSCs develop and progress. We have developed transgenic (Ovgp1-iCreERT2) mice allowing conditional (tamoxifen [TAM]-inducible) expression of Cre recombinase exclusively in the oviductal epithelium, using a single transgene. Using double transgenic Ovgp1-iCreERT2;R26LSL-eYFP mice in which TAM treatment activates eYFP reporter protein expression in oviductal epithelial cells, we have shown that tubal-type inclusion glands (endosalpingiosis) expressing both eYFP and OVGP1 are present in a subset of murine ovaries following treatment with TAM. The findings suggest that oviductal epithelium can detach from the oviduct and traffic to the ovaries, where it implants through breaks in the OSE and maintains its tubal-type differentiation. Preliminary data also suggest that the frequency of ovarian endosalpingiosis increases over time and by superovulating the mice. The latter finding raises the possibility that at least some of the protective effects of high parity and oral contraceptive use on human ovarian cancer risk is related to reduced likelihood of acquiring endosalpingiosis from which “ovarian” HGSCs may eventually arise. We have further shown that Ovgp1-iCreERT2;Trp53fl/fl;Brca1fl/fl mice develop oviductal lesions identical to human serous tubal intraepithelial carcinomas (STICs) after TAM treatment and have identified additional genetic alterations that cooperate with Trp53 and Brca1 inactivation in oviductal HGSC pathogenesis in our model system. Murine models of HGSC that recapitulate their human tumor counterparts provide excellent in vivo systems with which to define the cellular and molecular events associated with HGSC development and progression. Citation Format: Yali Zhai, Rong Wu, Tom C. Hu, Eric R. Fearon, Kathleen R. Cho. Development and characterization of an oviduct-specific model of high-grade serous carcinoma [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr AS06.
231. A Stem Cell Approach for Cancer Blood Test
Authors: Linan Liu, Shirley X. Zhang, Rangoli Aeran, Wenbin Liao, Mengrou Lu, George Polovin, Egest J. Pone, Weian Zhao
Journal: Molecular Therapy (2015)

Mesenchymal stem cells (MSC) are adult multipotent stem cells that possess regenerative and immunomodulatory properties. They have been widely investigated as therapeutic agents for a variety of disease conditions, including tissue repair, inflammation, autoimmunity and organ transplantation. Importantly, systemically-infused MSC selectively home to primary and metastatic tumors, though the molecular mechanisms of tumor tropism of MSC remain incompletely understood. We have exploited the active and selective MSC homing to cancer microenvironments to develop a rapid and selective blood test for the presence of cancer. Here we present the concept of using transplanted MSC as the basis for a simple cancer blood test. MSC engineered to express humanized Gaussia luciferase (hGluc) co-localize with and persist in cancerous tissue, secreting hGluc into circulation that can be assayed in a minimally invasive fashion as a reporter for cancer presence. In vitro, hGluc secreted by engineered MSC can be detected stably over a period of days in the presence of serum. In vivo imaging showed that MSC homed to breast cancer lung metastases and persisted longer in tumor-bearing mice than in tumor-free mice (P < 0.05). hGluc activity in blood of tumor-bearing mice was significantly higher than in their tumor-free counterparts (P < 0.05). Both in vitro and in vivo data show that MSC expressing hGluc can identify and report small tumors or metastases in a simple blood test format. Our novel and simple stem cell-based blood test can potentially be used to screen, detect and monitor cancer and metastasis at early-stages and during treatment.
Anti-angiogenic Nanotherapy Inhibits Airway Remodeling and Hyper-responsiveness of Dust Mite Triggered Asthma in the Brown Norway Rat
Authors: Gregory M. Lanza, John Jenkins, Anne H. Schmieder, Aigul Moldobaeva, Grace Cui, Huiying Zhang, Xiaoxia Yang, Qiong Zhong, Jochen Keupp, Ismail Sergin, Krishna S. Paranandi, Lindsey Eldridge, John S. Allen, Todd Williams, Michael J. Scott, Babak Razani, Elizabeth M. Wagner
Journal: Theranostics (2016)

Although angiogenesis is a hallmark feature of asthmatic inflammatory responses, therapeutic anti-angiogenesis interventions have received little attention. Objective: Assess the effectiveness of anti-angiogenic Sn2 lipase-labile prodrugs delivered via αvβ3-micellar nanotherapy to suppress microvascular expansion, bronchial remodeling, and airway hyper-responsiveness in Brown Norway rats exposed to serial house dust mite (HDM) inhalation challenges. Results: Anti-neovascular effectiveness of αvβ3-mixed micelles incorporating docetaxel-prodrug (Dxtl-PD) or fumagillin-prodrug (Fum-PD) were shown to robustly suppress neovascular expansion (p<0.01) in the upper airways/bronchi of HDM rats using simultaneous 19F/1H MR neovascular imaging, which was corroborated by adjunctive fluorescent microscopy. Micelles without a drug payload (αvβ3-No-Drug) served as a carrier-only control. Morphometric measurements of HDM rat airway size (perimeter) and vessel number at 21d revealed classic vascular expansion in control rats but less vascularity (p<0.001) after the anti-angiogenic nanotherapies. CD31 RNA expression independently corroborated the decrease in airway microvasculature. Methacholine (MCh) induced respiratory system resistance (Rrs) was high in the HDM rats receiving αvβ3-No-Drug micelles while αvβ3-Dxtl-PD or αvβ3-Fum-PD micelles markedly and equivalently attenuated airway hyper-responsiveness and improved airway compliance. Total inflammatory BAL cells among HDM challenged rats did not differ with treatment, but αvβ3+ macrophages/monocytes were significantly reduced by both nanotherapies (p<0.001), most notably by the αvβ3-Dxtl-PD micelles. Additionally, αvβ3-Dxtl-PD decreased BAL eosinophil and αvβ3+ CD45+ leukocytes relative to αvβ3-No-Drug micelles, whereas αvβ3-Fum-PD micelles did not. Conclusion: These results demonstrate the potential of targeted anti-angiogenesis nanotherapy to ameliorate the inflammatory hallmarks of asthma in a clinically relevant rodent model.
Primary angle closure glaucoma: What we know and what we don’t know
Authors: Xinghuai Sun, Yi Dai, Yuhong Chen, Dao-Yi Yu, Stephen J. Cringle, Junyi Chen, Xiangmei Kong, Xiaolei Wang, Chunhui Jiang
Journal: Progress in Retinal and Eye Research (2016)

Primary angle-closure glaucoma (PACG) is a common cause of blindness. Angle closure is a fundamental pathologic process in PAGC. With the development of imaging devices for the anterior segment of the eye, a better understanding of the pathogenesis of angle closure has been reached. Aside from pupillary block and plateau iris, multiple-mechanisms are more common contributors for closure of the angle such as choroidal thickness and uveal expansion, which may be responsible for the presenting features of PACG. Recent Genome Wide Association Studies identified several new PACG loci and genes, which may shed light on the molecular mechanisms of PACG. The current classification systems of PACG remain controversial. Focusing the anterior chamber angle is a principal management strategy for PACG. Treatments to open the angle or halt the angle closure process such as laser peripheral iridotomy and/or iridoplasty, as well as cataract extraction, are proving their effectiveness. PACG may be preventable in the early stages if future research can identify which kind of angles and/or persons are more likely to benefit from prophylactic treatment. New treatment strategies like adjusting the psychological status and balancing the sympathetic-parasympathetic nerve activity, and innovative medicines are needed to improve the prognosis of PACG. In this review, we intend to describe current understanding and unknown aspects of PACG, and to share the clinical experience and viewpoints of the authors.
Abstract 1350: The combination of a murine iNKT cell-activating antibody and IL-12 exhibits antitumor activity in a mouse melanoma model
Authors: Weiming Yuan, Xiangshu Wen
Journal: Cancer Research (2015)

Abstract Invariant natural killer T (iNKT) cells are innate-like T cells with an invariant iTCR with potent anti-tumor activity. Current anti-tumor clinical trials using the iNKT cell ligand, a-galactosylceramide (a-GalCer) have had limited success. One major limitation of a-GalCer-based therapies is the bioavailability of lipid drugs and current therapies require isolation and a-GalCer loading of dendritic cells prior to administration (Richter et al Blood 121:423, 2013). We have engineered a murine iNKT TCR-targeting monoclonal antibody (NKT14m) that activates iNKT cells directly without dendritic cells or glycolipids. We have evaluated the in vivo anti-tumor efficacy with the established B16 mouse melanoma model. Based on preliminary results that the potency of NKT14m is less than that of a-GalCer, we reasoned that the addition of IL-12 stimulation would be beneficial for iNKT cell activation (Yue et al PNAS 102:11811, 2005). Currently, the toxicity of IL-12 has restricted its use in clinical trials. We evaluated a non-toxic dose of IL-12 alone and in combination with NKT14m. C57BL/6 mice were injected with 400K B16F10 melanoma cells on Day 0. On Day 2 they were divided into untreated, IL-12 treated (0.1 ug/mouse/day for 12 days), NKT14m treated (100 ug/mouse once on Day 2) and the combination of NKT14m+IL-12 using the same dose regimens. On Day 14 mice were sacrificed and lung tumors counted. We detected a synergistic effect in the combination of NKT14m+IL-12 (Table 1). These findings represent a new paradigm of iNKT cell activation for their anti-tumor function. Table 1 - Lung Tumors in Treatment GroupsExperimental GroupsControlIL-12NKT14mIL-12+NKT14mNumbers of metastatic tumors150+/-67117+/-2555+/-2923+/-10 Citation Format: Weiming Yuan, Xiangshu Wen. The combination of a murine iNKT cell-activating antibody and IL-12 exhibits antitumor activity in a mouse melanoma model. [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 1350. doi:10.1158/1538-7445.AM2015-1350
Abstract 2202: Novel regulation of pro-migratory genes by nuclear Src in pancreatic cancer cells
Authors: David Paladino
Journal: Cancer Research (2015)

Abstract Pancreatic cancer is an exceptionally lethal malignancy with a poor prognosis, and there is little known about the molecular mechanisms that lead to the disease and its progression. Several reports have implicated dysregulated Src tyrosine kinase function in pancreatic tumorigenesis and progression. However, except for the classic role of Src in promoting events that contribute to invasiveness, not much is known of how the tyrosine kinase supports pancreatic cancer progression and the poor response of the disease to therapy. In previous reports, we showed that Src is present in the cell nucleus of pancreatic cancer cells in association with gene promoter sequences. Mass spectrometry analysis of Src co-immune complex from nuclear lysate preparations from pancreatic cancer cells identified p300 as a novel Src-interacting protein. Chromatin immunoprecipitation coupled to human promoter microarray (ChIP-chip) analysis showed that nuclear Src is associated with the promoters of SMYD3 and HMGA2 in pancreatic cancer cells. Inhibition of Src tyrosine kinase or p300 lysine acetyltransferase activity decreased the expression of SMYD3 and HMGA2 mRNA and protein levels in pancreatic cancer cells in a time-dependent manner and blocked pancreatic cancer cell migration. Current data altogether show that Src at the inner nuclear envelope is physically associated with and regulates the expression of SMYD3 and HMGA2, through interaction with p300. The studies identify a novel Src function through epigenetic regulation of pro-metastatic genes and provide additional potential avenues for developing new treatment strategies for metastatic pancreatic cancer. Citation Format: David Paladino. Novel regulation of pro-migratory genes by nuclear Src in pancreatic cancer 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 2202. doi:10.1158/1538-7445.AM2015-2202
Research Across Borders
Authors: Jeff Lyon
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Activity of Bosutinib by Baseline and Emergent Mutation Status in Philadelphia Chromosome–Positive Leukemia Patients with Resistance or Intolerance to Other Tyrosine Kinase Inhibitors
Authors: H. Jean Khoury, Jorge E Cortes, Carlo Gambacorti-Passerini, Dong-Wook Kim, Andrey Zaritskey, Andreas Hochhaus, Eric Leip, Nadine Besson, Virginia Kelly, Tim H Brümmendorf
Journal: Blood (2011)
P291 In-use stability of aclidinium bromide 400 μg/formoterol fumarate dihydrate 12 μg inhalation powder in a dry powder inhaler
Authors: S Linne-Geyer, K Stahl, T Pieper
Journal: Thorax (2016)

<h3></h3> Three stability studies simulating patient use were performed on aclidinium bromide 400 μg/formoterol fumarate dihydrate 12 μg inhalation powder in the Genuair™* inhaler. Samples of a development batch representative for commercial production were tested after corresponding pre-storage for 12, 22, and 35 months over an in-use period of 10 weeks, at climatic zone II and IVb conditions. At day 0 and appropriate time intervals until the final dose was dispensed and the lock-out mechanism of the inhaler was activated, the following parameters were assessed: water content, degradation products, content per cartridge, delivered dose (DD), fine particle dose (FPD) and microbial growth. All results, notably DD and FPD (Figure 1), were within the expected range and well inside the specifications applied during development. More precisely, the mean results of DD for aclidinium bromide were between 370 µg and 451 µg (specification 320–480 µg) and for FPD between 139 µg and 182 µg (specification ≥80µg), while the mean values of DD for formoterol fumarate dihydrate were between 10.1 µg and 13.1 µg (specification 9.6–14.4 µg) and for FPD between 2.5 µg and 3.7 µg (specification ≥1.8 µg). The studies show that stable pharmaceutical quality can be guaranteed under in-use conditions for a period longer than the allowed 60 days after unpacking the drug product pre-stored even up to the end of shelf life. *Registered trademark of AstraZeneca group of companies; for use within the USA as Pressair® and Genuair™ within all other licensed territories.
Falling Serum Albumin Predicts Severity of Acute Graft-Vs.-Host Disease and Non-Relapse Mortality After Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation.
Authors: Andrew R. Rezvani, Barry E. Storer, Rainer F. Storb, Marco Mielcarek, David G. Maloney, Brenda M. Sandmaier, Paul J. Martin, Mary E. D. Flowers, George B. McDonald
Journal: Blood (2009)
197. Survival, Growth, and Neurobehavioral Outcomes in a Mouse Model of Menkes Disease With CSF-Directed AAV9 and Subcutaneous Copper Histidine
Authors: Marie Reine Haddad, Diego Martinelli, Eun-Young Choi, Patricia M. Zerfas, Patricia Sullivan, David S. Goldstein, Daniel T. Abebe, Jose A. Centeno, Stephen G. Kaler
Journal: Molecular Therapy (2015)

Menkes disease is a X-linked recessive neurometabolic disorder with high morbidity and mortality caused by a defective transmembrane copper transporter, ATP7A. The mottled-brindled (mo-br), a Menkes mouse model, has afforded the chance to compare clinical, biochemical, and pathological outcomes in response to specific therapeutic interventions, including rAAV5-, rAAVrh10-, and most recently, rAAV9-ATP7A viral gene therapy. The rAAV9 and rAAVrh.10 serotypes show broader neuronal tropism than rAAV5 and may gain access to the brain after systemic administration. However, the seroprevalence of maternally transmitted neutralizing antibodies against AAV in human infants from birth to 6 months suggests that peripheral administration could be suboptimal in our target population. Thus, cerebrospinal fluid (CSF)-directed rAAV9- or rAAVrh.10-ATP7A appear to represent a more suitable choice from both immunological and tissue target perspectives. In mo-br mice, we evaluated intracerebroventricular administration of rAAV9- and rAAVrh10-ATP7A, using low, medium, and high doses in affected mutants on day 2 of life, with 15 μg of clinical grade copper histidine given by subcutaneous injection between d4 and d10. Survival data from a cohort of 40 mo-br mice documented that intermediate (5.0×109 vg) and high (1.6×1010 vg) rAAV9-ATP7A doses were most effective. In correlation with the best survival benefit, CSF-directed rAAV9 + subcutaneous Cu resulted in superior murine neurobehavioral outcomes and "catch-up" growth compared to results with other serotypes, reported previously. In addition, mutant mice treated with high dose AAV9+Cu showed the highest brain viral genome copies, and markedly improved brain neurochemical and brain copper levels in comparison to untreated mutants. Brain copper measurements in combination-treated mutants (d12) were not statistically different in comparison to wild type littermates. Based on our combined data, we propose rAAV9 as a serotype of choice for first-in-human intrathecal administration in patients with Menkes disease.