tbuckley/cabot-search huggingface dataset:
Abstract #2336: Anti-PAK1 products Bio 30 and Brazilian green propolis extract (GPE) suppress the growth of human NF and glioma xenografts in mice
Authors: Shanta Messerli, Maria Demestre, Mok-Ryeon Ahn, Miyako Yanagihara, Tomoki Tatefuji, Yoshihiro Uto, Hitoshi Hori, Victor Mautner, Ken Hashimoto, Shigenori Kumazawa, Toshiro Ohta, Hiroshi Maruta
Journal: Cancer Research (2009)

More than 70% of human cancers including breast, pancreatic cancer and glioma as well as neurofibromatosis (NF) tumors require the kinase PAK1 for their growth. Although there are a few pure chemical compounds such as FK228 and CEP-1347 that directly or eventually block the oncogenic PAK1 signaling pathways, so far none of them is available for the treatment of these formidable tumors. We have identified a few natural anti-PAK1 products including Bio 30, a caffeic acid phenethyl ester (CAPE) -rich water-miscible extract of propolis from New Zealand (NZ) and the anti-cancer polyphenol Artepillin (ARC)-rich Brazilian green propolis extract (GPE) which block the growth of NF tumors in mouse xenograft models. CAPE is an anti-cancer polyphenol primarily derived from young buds of poplar trees, which is collected by honey bees to make honey combs. We previously demonstrated that CAPE and ARC selectively block the PAK1 signaling pathways in cell culture. Naturally CAPE-based Bio 30, and ARC-based GPE block the growth of both NF1 and NF2 tumor cells in vitro. Furthermore, Bio 30 (100 mg/kg, intraperitoneal (i.p.) twice a week) almost completely blocks the growth of both human malignant peripheral nerve sheath tumors (MPNST) NF1 tumors and NF2 schwannomas as well as grade-4 glioma xenografts in mice. Similarly GPE (500 mg/kg, i.p., twice a week) almost completely suppresses the growth of NF2 tumor xenograft in mice . Currently clinical Bio 30 trials for NF and glioma patients are in progress.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2336.
High-Dose Statins in Acute Coronary Syndromes
Authors: John R Crouse
Journal: JAMA (2005)

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
Autosomal-dominant giant platelet syndromes: a hint of the same genetic defect as in Fechtner syndrome owing to a similar genetic linkage to chromosome 22q11-13
Authors: Amos Toren, Galit Rozenfeld-Granot, Bianca Rocca, Charles J. Epstein, Ninette Amariglio, Ferdinando Laghi, Raffaele Landolfi, Frida Brok-Simoni, Lena E. Carlsson, Gideon Rechavi, Andreas Greinacher
Journal: Blood (2000)
The changing distribution pattern of H1N1 infection in adults in 2010-2011
Authors: Matthew Harris, Suzanne Shuttleworth, Sebastien Ellis, Christopher Taylor, Benjamin Marshall, Aye Aye Lwin
Journal: European Respiratory Journal (2011)

Background:  Since the emergence of H1N1 influenza in 2009, the World Health Organization (WHO) identified that patients with co-morbidities, pregnant women, and those over 65 years are at high risk of severe complications.   Aims and objectives:  To characterise adult patients admitted with H1N1, particularly those with pneumonia, or those requiring intensive care unit (ICU) admission.   Methods:  H1N1 positive inpatients from December 2010 to January 2011 were studied using electronic patient records, medical notes and the PACS system. Co-morbidities are recognized as per WHO guidance.   Results:  In total 76 patients were admitted with H1N1, 32 male and 44 female with a median age of 39 years (range 18-79). 71 were under 65 years, 28 had no co-morbidities and 9 were pregnant.  35 patients with H1N1 had radiological evidence of consolidation, 8 were associated with a pleural effusion and 3 required a chest drain. 29 of 35 were under 65 years and 16 had no co-morbidities. None of the 35 patients with pneumonia were pregnant.  Of the 35 cases with H1N1 pneumonia, 19 were escalated to the ICU (14 male and 5 female) with a median age of 43 years (range 26-53). In 8 out of the 19 ICU patients there were no co-morbidities; within this group 1 died of acute lung injury with multi-organ failure.   Conclusions:  Our study highlighted that patients under 65 years, particularly males without co-morbidities had an increased risk of severe H1N1 infection compared to those in 2009. This patient group should therefore be considered for vaccination against H1N1; however larger studies are required to characterise this group.
IgG Subclass Antibody Response in Grass Pollen‐Allergic Patients Undergoing Specific Immunotherapy
Authors: R. Djurup, O. ØSterballe
Journal: Allergy (1984)

All four subclasses of IgG antibodies to timothy grass pollen extract were measured by a three‐layer immunoradiometric assay in sera from 20 grass pollen‐allergic patients who underwent specific immunotherapy in a 3‐year prospective study. Both IgG1 and antibody level passed its peak (median 5,4 U/ml) after 12 weeks. At this time, the ratio between the medians of IgG1 and IgG4 antibodies was 2.25 IgG4 antibody level reached its peak (median 11.6 U/ml) just before termination of immunotherapy. At this time IgG1/IgG4 ratio was 0.43. Two years after the end of immunotherapy, IgG1 and IgG4 antibody levels were 0.0 and 1.8 U/ml in median, respectively. The amounts of IgG2 and IgG3 antibodies detected in the sera were less than 1.6 U/ml and were considerd insignificant. Preseasonal serum IgG1 and IgG4 antibody levels did not correlate significantly with symptom scores in the subsequent season. Serum IgG4 level obtained after 12 weeks of immunotherapy was significantly correlated to symptom score in the third season i.e. the season just after termination of therapy ( r s =0.529. t = 2.567. P = 0.02). In this work. A scrum IgG4 antibody level higher than 8.0 U/ml after 12 weeks of therapy predicted poor clinical result at the end of immunotherapy with 100% sensitivity and 87% specificity. An IgG4/IgG1 ratio greater than 1.0 after 12 weeks' therapy had the same predictive value.
Abstract 347: Dasatinib accelerates valproic acid-induced acute myeloid leukemia cells death by regulation of differentiation capacity
Authors: Sook-Kyoung Heo, Eui-Kyu Noh, Dong-Joon Yoon, Jae-Cheol Jo, Jae-Hoo Park, Hawk Kim
Journal: Cancer Research (2014)

Abstract Dastinib (BMS-354825) is a FDA-approved small compound that was developed for chronic myeloid leukemia as a multi-targeted kinase inhibitor of wild-type BCR-ABL and SRC family kinases. Valproic acid (VPA; Orfiril) has been a well-known anti-epileptic drug worldwidely, and belong to the class I histone deacetylase inhibitor. The aim of this research is to determine the anti-leukemic effects of combination of dasatinib and VPA or their mechanism in acute myeloid leukemia (AML) cells. In this study, dasatinib showed potent inhibitory effects on VPA-treated AML cells that were associated with induced G1 phase cell cycle arrest and also apoptosis including the cleavage of PARP, caspase-3, -7 and -9. Moreover, inhibitors of caspase-3 and -9 (Z-DEVD-FMK and LEHD-CHO) efficiently inhibited dasatinib-induced apoptosis in VPA-treated AML cells. Therefore, dasatinib/VPA-induced cell death occurred via caspase-dependent apoptosis. Also, inhibitors of MEK/ERK (U0126 and PD98059) and p38 MAPK (SB203580) efficiently inhibited dasatinib/VPA-induced apoptosis. The combination of dasatinib and VPA differentiation capacity of AML cells is more powerful than each drug alone. So the combination is enough to push AML cells to death strongly by G1 cell cycle arrest and caspase-dependent apoptosis. In addition, MEK/ERK and p38 MAPK controls dasatinib/VPA-induced apoptosis as an upstream regulator. Finally, co-treatment of dasatinib and VPA is contributed to AML cell death by regulation of differentiation capacity. Taken together, these results indicate that dasatinib and VPA together have a potential for anti-leukemic therapy. Citation Format: Sook-Kyoung Heo, Eui-Kyu Noh, Dong-Joon Yoon, Jae-Cheol Jo, Jae-Hoo Park, Hawk Kim. Dasatinib accelerates valproic acid-induced acute myeloid leukemia cells death by regulation of differentiation capacity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 347. doi:10.1158/1538-7445.AM2014-347
In adults without CV disease, most prediction scores overestimated risk for atherosclerotic CV events
Authors: Ann Marie Navar, Michael Pencina
Journal: Annals of Internal Medicine (2015)

Source Citation DeFilippis AP, Young R, Carrubba CJ, et al. An analysis of calibration and discrimination among multiple cardiovascular risk scores in a modern multiethnic cohort. Ann Intern Med. 2015;162:266-75. 25686167
Abstract 1802: Small molecule compound NCI-8 induces mutant p53 degradation via inhibition of the MDM2-Hsp90 axis
Authors: Shengliang Zhang, Lanlan Zhou, Christina Leah B. Kline, David T. Dicker, Wafik S. El-Deiry
Journal: Cancer Research (2014)

Abstract The tumor suppressor p53 prevents cancer development via regulating cell cycle arrest, cell death, or repair processes. Over 50% of human cancers harbor mutant p53. Mutations in p53 not only abrogate its tumor suppressor function, but also endow mutant p53 with a gain-of-function (GOF), creating a proto-oncogene that contributes to tumorigenesis, tumor progression and chemotherapeutic resistance. Thus, targeting mutant p53 to restore wild-type p53 pathway signaling is an attractive strategy for cancer therapy. We previously reported a novel small molecular compound, NCI-8, which not only restores wild-type p53 signaling, but also depletes mutant p53 protein (Zhang S, Zhou L, Hong B, et al. Cancer Res 2013;73(8 Suppl):Abstract 2171). In this study, we further elucidate the mechanism of the small molecular compound NCI-8-mediated degradation of mutant p53 protein. We found that the small molecule NCI-8 induces mutant p53 protein degradation via the MDM2-ubiquitin-proteasome pathway. NCI-8 exposure leads to phosphorylation of p53 at Thr55. Dephosphorylation of p53 at Thr55 rescues mutant p53 protein from degradation in cells treated with Apigenin, suggesting that phosphorylation at Thr55 is required for mutant p53 protein degradation induced by NCI-8. Hsp90 and hsp70 are two molecular chaperones that stabilize mutant p53 protein by affecting the MDM2 mediated turnover of mutant p53, therefore, we investigated the effect of NCI-8 on the MDM2-hsp chaperone axis. We found that less HSP90 but more MDM2 were bound to mutant p53 in cells treated with NCI-8, suggesting that NCI-8 induces mutant p53 protein degradation through disturbing the MDM2-hsp chaperone axis. Correlated to the degradation of mutant p53 protein, the p73 pathway was activated in response to NCI-8 treatment specifically in mutant p53-expressing colorectal cancer cells. Our results provide a possible mechanism of NCI-8-mediated p73-dependent restoration of the p53 pathway via mutant p53 protein degradation. Citation Format: Shengliang Zhang, Lanlan Zhou, Christina Leah B. Kline, David T. Dicker, Wafik S. El-Deiry. Small molecule compound NCI-8 induces mutant p53 degradation via inhibition of the MDM2-Hsp90 axis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1802. doi:10.1158/1538-7445.AM2014-1802
Contribution of immunohistochemical (IHC) markers to the diagnosis of pulmonary carcinoids
Authors: Tina Zahel, Arne Warth, Esther Herpel, Benjamin Goeppert, Albrecht Stenzinger, Sabine Krysa, Hans Hoffmann, Peter Schirmacher, Philipp Schnabel
Journal: European Respiratory Journal (2011)

Introduction: Data about prevalence and clinicopathological meaning of IHC markers in pulmonary typical (TC; n=114) and atypical (AC; n=86) carcinoids is still debated. The goal of this study was to present expression patterns of several IHC markers in TC and AC, to get an insight on differential diagnostic, prognostic, and potential therapeutic value.

Methods: 200 pulmonary carcinoid tumors were investigated for tissue distribution of: CD56, CD57, Chromogranin A, Synaptophysin, TTF-1, CK18, KL1, ERCC1, EGFR, and Her-2/neu. Ki67 was employed and the proliferative index (PI) was counted on whole slides of resected specimens.

Results: Mean PI was 1.8% in TC and 3.7% in AC and was significantly different in both groups (p<0.0001).Correlation between PI and mean mitotic count was significant. Furthermore, max PI correlated significantly with outcome. Established neuroendocrine markers Synapthophysin, Chromogranin A, and N-CAM (CD56) were strongly positive. Synaptophysin was expressed with highest intensity of all markers in 95.4% TC and 98.6% AC. Thyroid transcription factor 1 (TTF-1) was positive in 73.0% TC and 77.0% AC. Only few cases expressed EGFR and Her2/neu.

Conclusions: Synaptophysin may be the most sensitive marker for neuroendocrine differentiation. Nevertheless, there is no specific marker to clearly separate TC from AC. We confirm that the PI, as determined by Ki67 staining is higher in AC than in TC and might be an ancillary tool for the distinction between TC and AC in addition to the mitotic rate. Moreover, the combination of PI and mitotic count in terms of a grading system may predict outcome more effectively than mitotic count alone and should be subject to further research.
Abstract 12250: Type 2 Myocardial Infarction: An Observational Study of Provoking Conditions, Management and In-Hospital Outcomes
Authors: Nathaniel Smilowitz, Matthew C Weiss, Asha M Mahajan, Kaitlyn Dugan, Rina Mauricio, Becky Naoulou, Eugenia Gianos, Binita Shah, Steven P Sedlis, Martha Radford, Harmony R Reynolds
Journal: Circulation (2014)

Background: Type 2 myocardial infarction (MI) is defined as myocardial necrosis due to an imbalance in supply and demand. Clinical characteristics predisposing to Type 2 MI and medical therapy use remain uncertain.

Methods: Charts of patients admitted to NYU Langone Medical Center in 2013 with a diagnosis of secondary myocardial ischemia (ICD9 411.89) or non-primary diagnosis of non-ST-elevation MI (ICD9 410.71) were retrospectively reviewed, following hospital standardization of acute MI ICD9 coding. Cases with suspected/confirmed Type 1 MI or without rise and fall of troponin were excluded.

Results: Charts of 104 inpatients with Type 2 MI have been reviewed to date, with evaluation of additional cases ongoing. Conditions associated with and possibly provoking Type 2 MI included sepsis (defined as SIRS with an infectious source, 39%), surgery (37%), anemia (Hgb  1.0 ng/mL (35%) were more likely to be discharged on aspirin (p=0.004) and beta-blocker (p=0.027), but not statin or ACEi.

Conclusions: Type 2 MI occurs most frequently in the setting of sepsis, surgery, and/or anemia in patients with cardiovascular risk factors, but mechanisms of Type 2 MI remain poorly understood. Rates of outpatient antiplatelet and statin prescription are low at hospital discharge, reflecting physician uncertainty about the role of secondary prevention. Further research into mechanisms is needed to inform management of patients with Type 2 MI.

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Abstract 4167: Harvesting knowledge from unexploited genomic data: Estimating relative telomere length from targeted-resequencing
Authors: Ogan D. Abaan, Joshua Waterfall, Sean Davis, Daniel Edelman, Allison Gomez, Sharon Savage, Yves Pommier, Paul Meltzer
Journal: Cancer Research (2014)

Abstract Telomeres play an essential role in maintaining the fidelity of chromosome ends during replication, but without an active telomere maintenance mechanism, their length decreases with each successive cell division. Aberrant telomere biology is a critical component of tumorigenesis. Replicative immortality is a hallmark of cancer and tumor cells circumvent cellular crisis associated with telomere shortening via two main mechanisms, activation of telomerase or the alternative lengthening of telomeres process (ALT). Targeted-resequencing, such as whole exome sequencing (WES), is becoming a tool for molecular diagnostics and gene discovery. While WES contains mostly data from the targeted region, a significant amount of off-target reads are not utilized for analysis. These off-target sequences likely contain additional information from the patients' genome that may be analyzed as well. Telomeric repeats, in general, are not targeted in WES, however due to their high abundance, they are present in the off-target fraction. We developed an algorithm that can estimate relative telomere length (RTL) using off-target reads from targeted-resequencing data. For proof-of-principle, we used the WES data for 14 osteosarcoma cell lines. RTL values calculated demonstrate correlations between lower RTL values in samples with hTERT expression and higher values in ALT positive cell lines, consistent with the known association of ALT and longer telomeres. In order to validate the algorithm's robustness, we evaluated published WES data for the NCI-60 panel of cell lines. The results suggest that most cells display the classic telomere shortening, while a few cell lines, such as LOX-IMVI, have long telomeres. These results will be compared to alternative techniques for measuring telomere length. In summary, we believe that this approach will enable utilization of otherwise overlooked off-target data generated by targeted-resequencing based molecular diagnostic tests. Citation Format: Ogan D. Abaan, Joshua Waterfall, Sean Davis, Daniel Edelman, Allison Gomez, Sharon Savage, Yves Pommier, Paul Meltzer. Harvesting knowledge from unexploited genomic data: Estimating relative telomere length from targeted-resequencing. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4167. doi:10.1158/1538-7445.AM2014-4167
Tropomyosin IgE-positive results are a good predictor of shrimp allergy
Authors: C. Gámez, S. Sánchez-García, M. D. Ibáñez, R. López, E. Aguado, E. López, B. Sastre, J. Sastre, V. del Pozo
Journal: Allergy (2011)

To cite this article: Gámez C, Sánchez-García S, Ibáñez MD, López R, Aguado E, López E, Sastre B, Sastre J, del Pozo V. Tropomyosin IgE-positive results are a good predictor of shrimp allergy. Allergy 2011; 66: 1375–1383. Background: Shrimp is a common cause of food allergy. Our aims were to determine the value of IgE antibodies in the diagnosis of shrimp allergy and to study red shrimp (Solenocera melantho) tropomyosin both as a new allergen and as a cross-reactive IgE-binding protein. Methods: We have studied 45 subjects. Skin prick test (SPT) was carried out in all subjects, and specific IgE (sIgE) to shrimp, recombinant and natural shrimp tropomyosins rPen a 1 and nPen m 1, recombinant Der p 10, and Dermatophagoides pteronyssinus was assessed by fluoroimmunoassay and/or immunoblotting. Double-blind, placebo-controlled food challenges were carried out to confirm diagnosis of shrimp allergy. Also, in vitro inhibition tests were performed to evaluate cross-reactivity. Results: Shrimp allergy was confirmed in 18 shrimp-allergic patients. Skin prick test and IgE antibodies to shrimp were positive in all shrimp-allergic patients; sIgE to rPen a 1 was detected in 98% of these patients. Of the 18 shrimp-tolerant patients, 61% had positive SPT to shrimp, 55% were IgE-positive to shrimp, and 33% showed IgE antibodies to rPen a 1. Determination of IgE to rPen a 1 yielded a positive predictive value of 0.72 and a negative predictive value of 0.91. Conclusion: IgE levels to rPen a 1 provided additional value to the diagnosis of shrimp allergy. Some allergens in mite extract are recognized by patients who are allergic to shrimp, though their clinical relevance remains unknown.
Analysis of allergen immunotherapy studies shows increased clinical efficacy in highly symptomatic patients
Authors: P. Howarth, H.‐J. Malling, M. Molimard, P. Devillier
Journal: Allergy (2011)

To cite this article: Howarth P, Malling H‐J, Molimard M, Devillier P. Analysis of allergen immunotherapy studies shows increased clinical efficacy in highly symptomatic patients. Allergy 2012; 67 : 321–327. Abstract Background: The assessment of allergen immunotherapy (AIT) efficacy in the treatment for seasonal allergic rhinoconjunctivitis (SAR) symptoms is challenging. Allergen immunotherapy differs from symptomatic therapy in that while symptomatic therapy treats patients after symptoms appear and aims to reduce symptoms, AIT is administered before symptoms are present and aims to prevent them. Thus, clinical studies of AIT can neither establish baseline symptom levels nor limit the enrolment of patients to those with the most severe symptoms. Allergen immunotherapy treatment effects are therefore diluted by patients with low symptoms for a particular pollen season. The objective of this analysis was to assess the effect possible to achieve with AIT in the groups of patients presenting the most severe allergic symptoms. Methods: Study centres were grouped into tertiles categorized according to symptom severity scores observed in the placebo patients in each centre (low, middle and high tertiles). The difference observed in the average score in each tertile in active vs placebo‐treated patients was assessed. This allowed an estimation of the efficacy that could be achieved in patients from sites where symptoms were high during the pollen season. Results: An increased treatment effect was observed in the most severe patients and was independent of the study analysed and symptom score used. Conclusions: The use of a tertile approach to analyse efficacy in AIT in SAR clinical studies can give a more accurate assessment of potential clinical benefit.