tbuckley/cabot-search huggingface dataset:
Development of Polymer Microcapsules Functionalized with Fucoidan to Target P‐Selectin Overexpressed in Cardiovascular Diseases
Authors: Bo Li, Maya Juenet, Rachida Aid‐Launais, Murielle Maire, Véronique Ollivier, Didier Letourneur, Cédric Chauvierre
Journal: Advanced Healthcare Materials (2016)

New tools for molecular imaging and targeted therapy for cardiovascular diseases are still required. Herein, biodegradable microcapsules (MCs) made of polycyanoacrylate and polysaccharide and functionalized with fucoidan (Fuco‐MCs) are designed as new carriers to target arterial thrombi overexpressing P‐selectin. Physicochemical characterizations demonstrated that microcapsules have a core–shell structure and that fucoidan is present onto the surface of Fuco‐MCs. Furthermore, their sizes range from 2 to 6 µm and they are stable on storage over 30 d at 4 °C. Flow cytometry experiments evidenced the binding of Fuco‐MCs for human activated platelets as compared to MCs (mean fluorescence intensity: 12 008 vs. 9, p &lt; 0.001) and its absence for nonactivated platelets (432). An in vitro flow adhesion assay showed high specific binding efficiency of Fuco‐MCs to P‐selectin and to activated platelet aggregates under arterial shear stress conditions. Moreover, both types of microcapsules reveal excellent compatibility with 3T3 cells in cytotoxicity assay. One hour after intravenous injection of microcapsules, histological analysis revealed that Fuco‐MCs are localized in the rat abdominal aortic aneurysm thrombotic wall and that the binding in the healthy aorta is low. In conclusion, these microcapsules appear as promising carriers for targeting of tissues characterized by P‐selectin overexpression and for their molecular imaging or treatment.
597. AAV. NT-3 Treatment Attenuates Spontaneous Autoimmune Peripheral Polyneuropathy
Authors: Mehmet E. Yalvac, William D. Arnold, Cilwyn Braganza, Lei Chen, Jerry R. Mendell, Zarife Sahenk
Journal: Molecular Therapy (2015)

The spontaneous autoimmune peripheral polyneuropathy (SAPP) model in B7-2 knockout non-obese diabetic (NOD) mice demonstrates overlapping clinical features with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Secondary axonal loss is prominent in the progressive phase of this neuropathy. Neurotrophin 3 (NT-3) is an important autocrine factor supporting Schwann cell (SC) survival and differentiation and stimulates neurite outgrowth and myelination. Recently, NT-3 delivered in bone marrow-derived neural stem cells was shown to exert therapeutic effect, by reducing the inflammation and accelerating remyelination in experimental encephalomyelitis (EAE), an animal model of multiple sclerosis. These findings led to considerations of AAV.NT-3 gene therapy via intramuscular delivery into SAPP mice to attenuate the disease. The results show AAV.NT-3 injection into gastrocnemius muscle of 25 week old SAPP mice produced measurable NT-3 levels in the serum at 7 weeks post gene delivery, sufficient to protect sciatic nerve motor function and compound muscle action potentials (CMAPs). Sciatic nerves of mice, receiving gene transfer had a significantly greater number of remyelinated fibers and decreased infiltration of CD3+ T cells compared to controls. These data correlated with reduced expression of the pro-inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor (Tnf-α) and increased expression of anti-inflammatory markers, interleukin-10 and forkhead box-P3 (Foxp3) in the sciatic nerve. The treatment also increased the percentage of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in the spleen. This proof-of-principle study established a therapeutic benefit by neuroprotective and immunomodulatory effects of AAV-NT-3 treatment in SAPP. This study demonstrates the potential clinical translational path for AAV delivered NT-3 for refractory cases of CIDP..
Abstract 2055: Overexpression of nuclear met activates NF-κB signaling to promote tumorigenesis and metastasis in hepatocellular carcinoma
Authors: Sze Keong Tey, Edith Yuk Ting Tse, Frankie Chi Fat Ko, Judy Wai Ping Yam
Journal: Cancer Research (2015)

Abstract Met is a surface receptor tyrosine kinase which upon hepatocyte growth factor (HGF) induction, triggers a diversity of downstream signaling cascades that modulates different cellular processes. Frequently, Met signaling pathway is hijacked in human cancers, resulted in abberant expression and activity. Emerging evidence has shown the presence of nuclear Met (nMet) in some cancerous tissues and cell lines, postulating that nMet could have unexplored functions within nucleus. Up to date, therapeutic antibodies and kinase inhibitos that undergoing clinical trial are all targeting Met surface receptor, which in this case exhibit limitation in acting against nMet. Althought Met is well known of its oncogenic role in hepatocellular carcinoma (HCC), existence and functions of nMet in HCC are yet to be reported. Our present study aim to examine the clinical association and functions of nMet in HCC. Immunohistochemistry of 103 human HCC paired samples showed that nMet was overexpressed in nearly 90% of cases. We also found that nMet overexpression was progressively increased along HCC development, from non-tumorous liver tissue to advanced HCC. Nonetheless, nMet overexpression was significantly associated with venous invasion and poorer overall survival in HCC patients. This suggests that nMet may play a pivotal role in HCC tumorigenesis and metastasis. As revealed by immunoblot and immunofluorescence, we found that nMet is about 48kDa and comprises of cytoplasmic domain of Met, as it can only be detected by an antibody against the carboxyl terminal of Met (C28). To study the functions of nMet, we employed a lentiviral based inducible exression system that tightly controlled by doxycycline to express the cytoplasmic region of Met. Immunofluorescence microscopy showed that juxtamembrane deletion of Met accumulates in the nucleus whereas truncated tyrosine kinase domain accumulates in the cytoplasm, implying a region necessary for nuclear localization of the cytoplasmic fragment. In vitro functional assay showed that nMet significantly promoted HCC cell proliferation and anchorage independent growth. It also significantly augmented HCC cell migration and invasiveness. Besides that, nMet also enhanced HCC tumor formation in animal model. Furthermore, we showed that nMet activates NF-κB reporter activity which might enhances the pro-metastatic gene expression to promote tumor invasiveness and aggressiveness. Citation Format: Sze Keong Tey, Edith Yuk Ting Tse, Frankie Chi Fat Ko, Judy Wai Ping Yam. Overexpression of nuclear met activates NF-κB signaling to promote tumorigenesis and metastasis in hepatocellular carcinoma. [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 2055. doi:10.1158/1538-7445.AM2015-2055
Fostamatinib Disodium (FosD), An Oral Inhibitor of Syk, Is Well-Tolerated and Has Significant Clinical Activity in Diffuse Large B Cell Lymphoma (DLBCL) and Chronic Lymphocytic Leukemia (SLL/CLL)
Authors: Jonathan W. Friedberg, Jeff Sharman, Julia Schaefer-Cutillo, Patrick B. Johnston, Sven De Vos, Ann LaCasce, John P. Leonard, Larry D. Cripe, Rajni Sinha, Stephanie A. Gregory, John Sweetenham, Julie M. Vose, Ann M Lowe, R. Levy, Margaret A. Shipp
Journal: Blood (2008)
DRES-08. METFORMIN OVERCOMES TEMOZOLOMIDE RESISTANCE OF GLIOMA CELLS BY MODULATING THE SOX2 PATHWAY
Authors: Seung Ho Yang, Shenglan Li, Guangrong Lu, Haipeng Xue, Dong H Kim, Jay-Jiguang Zhu, Ying Liu
Journal: Neuro-Oncology (2016)

The recurrence of glioblastoma multiforme (GBM) after standard therapy with temozolomide (TMZ) is a crucial issue to be solved. O6-methylguanine-DNA methyltransferase (MGMT) is known to be involved in TMZ resistance. Obtaining better understanding of chemoresistance mechanism is mandatory to improve clinical outcome. Sex-determining region Y-box 2 (SOX2) is of vital importance in the regulation of stem cell proliferation and carcinogenesis. We generated TMZ-resistant U251 and TMZ-resistant U87 subclones, and evaluated the role of SOX2 in TMZ chemoresistance. SOX2 expression was significantly increased in resistant cells than that of its parental cells. TMZ-resistant cells showed more capacity of migration, invasion and neurosphere formation. Our findings suggest that TMZ-resistant cells gain the similar activity with cancer stem cells. Metformin, a first-line treatment of type-2 diabetes has been shown to selectively kill cancer stem cells. Properties of TMZ-resistant cells were investigated before and after metformin treatment. These cells lost their aggressiveness and showed a decrease of SOX2 expression. Interestingly, it was found that they were partially re-sensitized to TMZ. DNA microarray was performed to analyze gene expressions of each cell groups. Our study indicates that SOX2 is associated with TMZ-resistance and it can be inhibited with metformin treatment.
Cost-effectiveness and Budget Effect Analysis of a Population-Based Skin Cancer Screening
Authors: Lore Pil, Isabelle Hoorens, Katrien Vossaert, Vibeke Kruse, Isabelle Tromme, Niko Speybroeck, Lieven Annemans, Lieve Brochez
Journal: JAMA Dermatology (2016)

Several epidemiological studies show an alarming global increase in incidence of melanoma and nonmelanoma skin cancer.To examine the cost-effectiveness of 2 population-based skin cancer screening methods and to assess their budget effect and the influence on skin cancer epidemiological findings.A Markov model with a latent period of 20 years and a time horizon of 50 years was used to analyze the cost-effectiveness (societal perspective) and budget effect (public health care payer perspective) of 2 population-based skin cancer screening programs in Belgium compared with the absence of a screening program. A health economic analysis was based on a clinical trial performed in 2014 in Belgium. In the economic model, the total Belgian population 18 years or older was assumed to have been invited for the screening program.The influence of the screening program on skin cancer epidemiological findings and the cost per quality-adjusted life-year (QALY) gained, as well as the budget effect, expressed as the net costs for the health care payer over 50 years.All participants (1668 total-body skin examination [TBSE] and 248 lesion-directed screening [LDS]) were screened by a team of 6 dermatologists from March 14 to 18, 2014, for TSBE and April 22 and 25 to 27, 2014, for LDS. Both screening strategies produced a gain in QALYs, resulting in incremental cost-effectiveness ratios of €33 072 (US $35 475) per QALY in men and €18 687 (US $20 044) per QALY in women for TBSE and €34 836 (US $37 365) per QALY in men and €19 470 (US $20 884) per QALY in women for LDS. With a 1-time screening, a 4.0% decrease in the incidence rates of stage III and IV melanoma was predicted at the population level relative to the comparator. The budget effect analysis demonstrated that during 20 years, a 1-time screening would incur a net cost for the health care payer of almost €36 million (US $38.6 million) for TBSE or just over €6 million (US $6.4 million) for LDS (€4.1 [US $4.40] or €0.7 [US $0.80], respectively, per adult).These results can be interpreted as cost-effective at a willingness-to-pay threshold in Belgium of €35 000 (US $37 541) per QALY gained. Based on these findings, a 1-time TBSE in the general adult population 18 years or older is the most cost-effective strategy and is predicted to result in a reduction of skin cancer mortality over 20 years and 50 years. The cost-effectiveness for skin cancer screening is higher in women than in men.
NCCN Guidelines Insights: Chronic Myeloid Leukemia, Version 1.2017
Authors: Arnel Pallera, Jessica K. Altman, Ellin Berman, Camille N. Abboud, Bhavana Bhatnagar, Peter Curtin, Daniel J. DeAngelo, Jason Gotlib, R. Tanner Hagelstrom, Gabriela Hobbs, Madan Jagasia, Hagop M. Kantarjian, Patricia Kropf, Leland Metheny, Joseph O. Moore, Evelena Ontiveros, Enkhtsetseg Purev, Albert Quiery, Vishnu V.B. Reddy, Michal G. Rose, Neil P. Shah, B. Douglas Smith, David S. Snyder, Kendra L. Sweet, Raoul Tibes, David T. Yang, Kristina Gregory, Hema Sundar, Michael Deininger, Jerald P. Radich
Journal: Journal of the National Comprehensive Cancer Network (2016)

The NCCN Guidelines for Chronic Myeloid Leukemia (CML) provide recommendations for the management of chronic-phase and advanced-phase CML in adult patients. The median age of disease onset is 67 years. However, because CML occurs in all age groups, clinical care teams should be prepared to address issues relating to fertility and pregnancy with patients who are of reproductive age at the time of diagnosis. CML is relatively rare in children and there are no evidence-based recommendations for the management of CML in pediatric population. These NCCN Guidelines Insights discuss special considerations for the management of CML during pregnancy and for the management of CML in the pediatric population.
Melanocortin 4 receptor is not required for estrogenic regulations on energy homeostasis and reproduction
Authors: Pingwen Xu, Liangru Zhu, Kenji Saito, Yongjie Yang, Chunmei Wang, Yanlin He, Xiaofeng Yan, Ilirjana Hyseni, Qingchun Tong, Yong Xu
Journal: Metabolism (2016)
When and How to Teach Residents to Operate
Authors: Marc D. Basson
Journal: JAMA Surgery (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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Surgery journal
In Vivo Labeling of Newly Synthesized DNA Suggests That the CD38+ Fraction Is Enriched in Proliferating Cells within a Clone of Chronic Lymphocytic Leukemia B Cells.
Authors: Carlo Calissano, Rajendra Damle, Taraneh Banapour, Denise Cesar, Marc Hellerstein, Steven Allen, Kanti Rai, Nicholas Chiorazzi
Journal: Blood (2006)
Urine Interleukin 18 and Lipocalin 2 Are Biomarkers of Acute Tubular Necrosis in Patients With Cirrhosis: A Systematic Review and Meta-analysis
Authors: Jeremy Puthumana, Xavier Ariza, Justin M. Belcher, Isabel Graupera, Pere Ginès, Chirag R. Parikh
Journal: Clinical Gastroenterology and Hepatology (2016)
Challenges for Conducting Clinical Trials Evaluating Maintenance Chemotherapy In Acute Myeloid Leukemia (AML): a Cancer and Leukemia Group B (CALGB) Study
Authors: William Blum, Kate Donohue, Guido Marcucci, Daniel J DeAngelo, Geoffrey L Uy, Bayard L Powell, Wendy Stock, Maria Baer, Jonathan E Kolitz, Meir Wetzler, Eva Hoke, Barry K Moser, Richard A Larson
Journal: Blood (2010)
324. Effect of Decorin-Expressing Adenovirus on Pathologic Fibrosis; Decreased Collagen Synthesis and Elevated MMP Expression
Authors: Hyo Min Ahn, Youjin Na, Il-Kyu Choi, Won Jai Lee, Yong Oock Kim, Ju Hee Lee, Dae Hyun Lew, Hyun Roh, Chae-Ok Yun
Journal: Molecular Therapy (2015)

Background: Decorin is a natural transforming growth factor-b1 (TGF-b1) antagonist. Reduced decorin synthesis is associated with dermal scarring and increased decorin expression appears to reduce scar tissue formation. To investigate the therapeutic potential of decorin for keloids, human dermal fibroblasts (HDFs) and keloid-derived fibroblasts (KFs) were transduced with decorin-expressing adenovirus (dE1-RGD/GFP/DCN), and we examined the therapeutic potential of decorin-expressing Ad for treating pathologic skin fibrosis Method: Decorin expression was examined by immunofluorescence assay on keloid tissues. HDFs and KFs were transduced with dE1-RGD/GFP/DCN or control virus, and protein levels of decorin, epidermal growth factor receptor (EGFR), and secreted TGF-β1 were assessed by western blotting and ELISA. And collagen type I, III, and MMP-1, 3 mRNA levels were measured by real-time RT-PCR. Additionally, we immunohistochemically investigated expression levels of the major extracellular matrix (ECM) proteins in keloid spheroids transduced with dE1-RGD/GFP/DCN. Results: Lower decorin expression was observed in the keloid region compared to adjacent normal tissues. After treatment with dE1-RGD/GFP/DCN, secreted TGF-βl and EGFR protein expression were decreased in TGF-b1-treated HDFs and KFs. Also, type I, III collagen mRNA levels were decreased and expression of MMP-1, 3 mRNA was strongly upregulated. In addition, expression of type I, III collagen, fibronectin, and elastin was significantly reduced in dE1-RGD/GFP/DCN-transduced keloid spheroids. Conclusion: These results support the utility of decorin-expressing adenovirus to reduce collagen synthesis in KFs and keloid spheroid, which may be highly beneficial in treating keloids.
Abstract 3778: Inhibition of NF-κB translocation induces G0/G1 arrest and downregulates thymidylate synthase in colorectal cancer
Authors: Ganji Purnachandra Nagaraju, Alese Olatunji, Sandhya Gupta, Mamoru Shoji, Bassel F. El-Rayes
Journal: Cancer Research (2015)

Abstract Purpose Objectives: Cell cycle progression and DNA synthesis are essential steps in cancer cell growth and resistance. Thymidylate synthase (TS) is a therapeutic target for 5FU. Curcumin is a potent inhibitor of NF-κB. We tested the hypothesis that NF-κB translocation inhibition by curcumin and its analogs can inhibit cell cycle progression and downregulate TS levels in colorectal cell lines. Methods: Two colorectal cancer cell lines were usedHCT-116 and HT-29. Cells were either untreated (control) or treated with curcumin (20μM), EF31 (7.5μM for HCT-116 and 2.5μM for HT-29) and UBS109 (620nM for HCT-116 and 1.25μM for HT-29) for 24 hours. Western blot and RT-PCR analyses were carried out to determine the effect of curcumin and its analogues EF31 and UBS109 on different signal molecules involved in cell cycle arrest and DNA synthesis. Electromobility shift assay (EMSA) was performed in colon cancer cells to evaluate the effects of curcumin and its analogues on NF-κB activity. A subcutaneous xenograft mouse model was used to evaluate the in vivo effects of curcumin analogues. Results: Treatment with curcumin and its analogues inhibited cyclin D1, pRb and E2F-1 at the transcriptional and translational level and induced p21, leading to G0/G1 cell cycle arrest. NF-κB over-expression induced E2F-1 and TS protein and mRNA levels in both cell lines. Arrest in the G0/G1 phase was associated with downregulation of the transcription factor E2F-1 and its target gene TS. Similar effects were observed in tumors from animals treated with EF31 and UBS109. Further, EF31 and UBS109 treatment significantly decreased the tumor growth compared to untreated tumors. Conclusion: In this study, we present in vitro and in vivo data to support the use of curcumin analogs in colorectal cancer based on their ability to reduce expression of proteins important for DNA repair and cell cycle progression leading to cell cycle arrest and tumor shrinkage. Accordingly, combining curcumin analogs with chemotherapy is a rational approach for future drug development in colorectal cancer. Citation Format: Ganji Purnachandra Nagaraju, Alese Olatunji, Sandhya Gupta, Mamoru Shoji, Bassel F. El-Rayes. Inhibition of NF-κB translocation induces G0/G1 arrest and downregulates thymidylate synthase in colorectal 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 3778. doi:10.1158/1538-7445.AM2015-3778
Hematopoietic Progenitor Cells From Patients with Chronic Mountain Sickness Lack the JAK2V617F Mutation, Show Hypersensitivity to Erythropoietin and Are Inhibited by Statins.
Authors: Ricardo Amaru, Martin Villarroel, Hortencia Miguez, Rosario Peñaloza, Gina Torres, Tiziano Barbui, Josee Golay, Alessandro Rambaldi
Journal: Blood (2009)
Association Between the Birth of an Infant With Major Congenital Anomalies and Subsequent Risk of Mortality in Their Mothers
Authors: Eyal Cohen, Erzsébet Horváth-Puhó, Joel G. Ray, Lars Pedersen, Nancy Adler, Anne Gulbech Ording, Paul H. Wise, Arnold Milstein, Henrik Toft Sørensen
Journal: JAMA (2016)

<h3>Importance</h3> Giving birth to a child with a major birth defect is a serious life event for a woman, yet little is known about the long-term health consequences for the mother. <h3>Objective</h3> To assess whether birth of an infant born with a major congenital anomaly was associated with higher maternal risk of mortality. <h3>Design, Setting, and Participants</h3> This population-based cohort study (n = 455 250 women) used individual-level linked Danish registry data for mothers who gave birth to an infant with a major congenital anomaly (41 508) between 1979 and 2010, with follow-up until December 31, 2014. A comparison cohort (413 742) was constructed by randomly sampling, for each mother with an affected infant, up to 10 mothers matched on maternal age, parity, and year of infant's birth. <h3>Exposure</h3> Live birth of an infant with a major congenital anomaly as defined by the European Surveillance of Congenital Anomalies classification system. <h3>Main Outcomes and Measures</h3> Primary outcome was all-cause mortality. Secondary outcomes included cause-specific mortality. Hazard ratios (HRs) were adjusted for marital status, immigration status, income quartile (since 1980), educational level (since 1981), diabetes mellitus, modified Charlson comorbidity index score, hypertension, depression, history of alcohol-related disease, previous spontaneous abortion, pregnancy complications, smoking (since 1991), and body mass index (since 2004). <h3>Results</h3> Mothers in both groups were a mean (SD) age of 28.9 (5.1) years at delivery. After a median (IQR) follow-up of 21 (12-28) years, there were 1275 deaths (1.60 per 1000 person-years) among 41 508 mothers of a child with a major congenital anomaly vs 10 112 deaths (1.27 per 1000 person-years) among 413 742 mothers in the comparison cohort, corresponding to an absolute mortality rate difference of 0.33 per 1000 person-years (95% CI, 0.24-0.42), an unadjusted HR of 1.27 (95% CI, 1.20-1.35), and an adjusted HR of 1.22 (95% CI, 1.15-1.29). Mothers with affected infants were more likely to die of cardiovascular disease (rate difference, 0.05 per 1000 person-years [95% CI, 0.02-0.08]; adjusted HR, 1.26 [95% CI, 1.04-1.53]), respiratory disease (rate difference, 0.02 per 1000 person-years [95% CI, 0.00-0.04]; adjusted HR, 1.45 [95% CI, 1.01-2.08]), and other natural causes (rate difference, 0.11 per 1000 person-years [95% CI, 0.07-0.15]; adjusted HR, 1.50 [95% CI, 1.27-1.76]). <h3>Conclusions and Relevance</h3> In Denmark, having a child with a major congenital anomaly was associated with a small but statistically significantly increased mortality risk in the mother compared with women without an affected child. However, the clinical importance of this association is uncertain.