tbuckley/cabot-search huggingface dataset:
Abstract P265: Adenosine 2A Receptor Activation Regulates Expression of Scavenger Receptors CD36 and LOX-1 in Human Macrophages and Aortic Endothelial Cells
Authors: Iryna Voloshyna, Michael J Littlefield, Steven Carsons, Allison B Reiss
Journal: Circulation Research (2011)

Objectives of the study. A variety of scavenger receptors (SR) have been linked to lipid accumulation in the vasculature. Among these, CD36 and LOX-1 are proposed to play a prominent role in atherosclerosis. Adenosine is a potent cellular signaling molecule with anti-atherogenic properties. Our previous work has shown that agonists specific for the adenosine A 2A receptor (A 2A R) enhance cholesterol efflux, preventing macrophage foam cell transformation. Here we report additional atheroprotective effects of A 2A R activation through changes in SR expression. Methods. Primary human aortic endothelial cells (HAECs) and THP-1 human macrophages were incubated in the presence of oxLDL (20 μg/ml) and: a) growth media b) DMSO vehicle c) the A 2A R agonist CGS-21680 (1 μM) d) the A 2A R antagonist ZM-241385 (10 μM, 1h) + CGS-21680 (1 μM) (n=5). SR expression was evaluated by real-time PCR. PCR results were confirmed by immunofluorescence analysis with CD36 and LOX-1-specific primary antibodies, followed by incubation with FITC conjugated secondary antibodies. Results. CGS-21680 downregulated CD36 and LOX-1 expression vs. untreated HAEC (67.89±9.55% and 49.00±2.55%, respectively, n=6, P&lt;0.01). This effect was abrogated by ZM-241385, resulting in upregulation of these SR to 175.9±22.67% and 172.10±39.6%, respectively, vs. control (n=6, P&lt;0.001). The pattern of SR expression changes in THP-1 macrophages upon exposure to CGS-21680 and ZM-241385 was the same as in HAEC. PCR results were confirmed by quantization of fluorescence intensity with immunofluorescence confocal microscopy. Summary. A 2A R activation is a promising therapeutic approach to prevent lipid overload in arterial vasculature. Our data support an anti-atherogenic role for the A 2A R in both cholesterol influx and efflux pathways. Several new agents that target the A 2A R are in development and they may hold promise as treatment for atherosclerotic cardiovascular disease.
Antitumor activity of lantadenes in DMBA/TPA induced skin carcinogenesis in mice: expression of transcription factors
Authors: jagdeep kaur, Manu Sharma, P Sharma, M Bansal
Journal: Clinical Cancer Research (2007)

A24  Various chemopreventive agents have been designed to prevent cancer. Lantadenes are class of triterpinoids extracted from noxious weed Lantana camara L. have antitumor activity, hence lantadenes which includes Lantadene A (LA) ; a pentacyclic triterpenoid and semisynthetically modified form of LA to its methyl ester (LAM) were used for present studies. LA and LAM were studied for its chemopreventive effect on 7,12-dimethylbenz(a)anthracene (DMBA) followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) induced squamous cell carcinoma in swiss albino mice. The skin lesions were induced by the twice-weekly topical application of DMBA (100nmol/100µl of acetone) for two weeks followed by TPA (1.7nmol/100µl of acetone) on shaved back of mice. LA and LAM were administered orally at maximum tolerated dose of 50mg/kg body weight twice a week, one week before DMBA application and continued 20 weeks thereafter. The earlier results of the study revealed a significant decrease in incidence and average number of papillomas in mice as compared to DMBA/TPA alone at the end of study. Hence, mRNA expression of various transcription factors was analyzed in tumors in comparison to untreated control mice skin. A significant increase in the levels of c-jun, c-fos, p65 and p53 was observed in DMBA/TPA treated mice tumors where as less expression of these transcription factors were observed in LA and LAM treated tumors. These findings were supported by histopathological studies in which presence of Keratinocyte pearls (KP) was observed in DMBA/TPA treated tumors where as KP were reduced in size and number, were observed in LA and LAM treated mice tumors.From the results, it can be inferred that LA and LAM possesses potential chemopreventive activity and may be linked to the expression of tumor suppressors.
Selective Effects of Psychotherapy on Frontopolar Cortical Function in PTSD
Authors: Gregory A. Fonzo, Madeleine S. Goodkind, Desmond J. Oathes, Yevgeniya V. Zaiko, Meredith Harvey, Kathy K. Peng, M. Elizabeth Weiss, Allison L. Thompson, Sanno E. Zack, Colleen E. Mills-Finnerty, Benjamin M. Rosenberg, Raleigh Edelstein, Rachael N. Wright, Carena A. Kole, Steven E. Lindley, Bruce A. Arnow, Booil Jo, James J. Gross, Barbara O. Rothbaum, Amit Etkin
Journal: American Journal of Psychiatry (2017)

Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but a comprehensive, emotion-focused perspective on how psychotherapy affects brain function is lacking. The authors assessed changes in brain function after prolonged exposure therapy across three emotional reactivity and regulation paradigms.Individuals with PTSD underwent functional MRI (fMRI) at rest and while completing three tasks assessing emotional reactivity and regulation. Individuals were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30) and underwent a second scan approximately 4 weeks after the last treatment session or a comparable waiting period, respectively.Treatment-specific changes were observed only during cognitive reappraisal of negative images. Psychotherapy increased lateral frontopolar cortex activity and connectivity with the ventromedial prefrontal cortex/ventral striatum. Greater increases in frontopolar activation were associated with improvement in hyperarousal symptoms and psychological well-being. The frontopolar cortex also displayed a greater variety of temporal resting-state signal pattern changes after treatment. Concurrent transcranial magnetic stimulation and fMRI in healthy participants demonstrated that the lateral frontopolar cortex exerts downstream influence on the ventromedial prefrontal cortex/ventral striatum.Changes in frontopolar function during deliberate regulation of negative affect is one key mechanism of adaptive psychotherapeutic change in PTSD. Given that frontopolar connectivity with ventromedial regions during emotion regulation is enhanced by psychotherapy and that the frontopolar cortex exerts downstream influence on ventromedial regions in healthy individuals, these findings inform a novel conceptualization of how psychotherapy works, and they identify a promising target for stimulation-based therapeutics.
Drug-Resistant Tuberculosis Predicted to Increase in High-Burden Countries
Authors: M.J. Friedrich
Journal: JAMA (2017)

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Infographics: Injury prevention exercise programmes: what are the perceptions of programme deliverers in the academy football setting?
Authors: Sheree Bekker, Caroline F Finch, James O’Brien
Journal: British Journal of Sports Medicine (2017)

Lower limb injuries are a common issue in professional association football (1). Injury prevention exercise programmes exist, but are not always effectively implemented (2). A survey of 18 participants, consisting of coaches (n=9), fitness coaches (n=4) and physiotherapists (n=5) working with elite European male junior football teams, was undertaken to find out what they think of exercise programmes designed to prevent lower limb injuries, so as to give clues about what could be done …
India cracks down on clinics offering stem cell therapy and blood cord banking
Authors: Sumi S Dutta
Journal: BMJ (2017)

The Indian government has updated national guidelines on stem cell research to help curb the indiscriminate use of stem cells in a range of conditions with no evidence.

The guidelines, published by the Indian Council of Medical Research (ICMR) and the Department of Biotechnology,1 are due come into force in August. They express concern about “therapeutic profligacy” and the exploitation of vulnerable patients without adequate efficacy and safety data.

The guidance states that stem cell therapy has been approved for only 18 haematological disorders in adults and nine in children, for three solid tumours in adults and eight in children, and for 10 non-malignant diseases in adults and 26 in children. Any other therapeutic uses …
Self report assessment and support for cancer symptoms: Impact on hospital admissions and emergency department visits.
Authors: Donna Lynn Berry, Fangxin Hong, Traci Blonquist, Barbara Halpenny, Mary Lou Siefert, Ann H. Partridge
Journal: Journal of Clinical Oncology (2013)

e20552 Background: Attending to symptoms and side effects promotes safe and effective delivery of cancer therapies. Educated and supported patients (Pts) may be able to self-manage symptoms (Sx) and know when to contact the clinician, avoiding emergency department visits (EDV) or hospital admissions (HA). The web-based Electronic Self Report Assessment for Cancer (ESRA-C) is an easy-to-use, automated program for assessing and teaching about symptom and quality of life issues (SQI) and has been shown to improve communication and reduce symptom distress over the course of active therapy. The purpose of this secondary analysis was to explore the impact of the ESRA-C intervention on rates of EDV and HA. Methods: AdultPts with all cancer types and stages treated in medical and radiation oncology at a comprehensive cancer center used ESRA-C to self-report SQI during new anti-cancer therapy, with summary reports delivered to clinicians. Patients were randomized to assessment-only ESRA-C (control) or the ESRA-C intervention adding self-monitoring and education and coaching between clinic visits. We analyzed group differences on EDV and HA using descriptive statistics and a two group unequal variance t-test. Results: Among 663 Pts, 34 out of 327 control Pts made 47 EDV vs 30 out of 336 intervention Pts made 42 visits. Likewise, 36 control Pts had 59 HA vs 36 intervention Pts who had 41 HA during the study duration. The majority of EDV (87%) and HA (88%) were Sx-related. The frequency of Sx-related events (EDV or HA) was higher in the control (n=94) vs the intervention group (n=71). The mean number of unplanned events were 0.29 and 0.21 per patient in the control and intervention groups, respectively (p=0.24). Conclusions: Although the trial sample size was not planned to test differences in EDV or HA, the ESRA-C intervention, compared with assessment alone, may have reduced symptom-related EDV and HA in a large sample of patients during active cancer treatment. If we are able to reduce Sx-related unplanned visits and admissions from more than 1 of 4 patients to 1 of 5 patients with an automated, patient-centered system, we can anticipate substantial cost savings when scaled to the volume of most comprehensive cancer centers. Clinical trial information: NCT00852852.
Proteasome and histone deacetylase inhibitors repress ErbB2 transcript levels and additively inhibit breast cancer growth.
Authors: Gary K. Scott, Corina Marx, Cliff Amend, Christopher Benz
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

2447 

We have reported on the development of a high-throughput tumor cell screening platform employing MCF-7 sublines bearing chromatin-integrated promoter-reporters (luciferase) capable of identifying from chemical libraries drug-like small molecules with tumor cell permeability and specific oncogene promoter-inhibiting potential. Among the structurally diverse lead compounds emerging from a screen to identify inhibitors of the ErbB2 promoter were a hydroxamic acid inhibitor of histone deacetylase (HDAC), trichostatin, further verified using more potent analogs now under clinical development including SAHA and LAQ824; and a synthetic peptide inhibitor of the proteasome, MG-132, further verified using the more potent and clinically approved dipeptidyl boronate, PS-341/bortezomib. Mechanistically, in addition to repressing ErbB2 promoter activity, both the HDAC and proteasome inhibitors destabilize mature cytoplasmic ErbB2 transcripts, inducing rapid (5 hr) declines in ErbB2 mRNA and protein levels as measured by Northern and Western blots of treated ErbB2-overexpressing breast cancer cells (MDA-453, SKBr3, BT-474). By comparison, proteasome and HDAC inhibitors show opposing effects on the expression of such other breast cancer gene products as ER and ESX. Investigations are currently underway to determine if proteasome inhibitors destabilize ErbB2 transcripts by the same 3’UTR-dependent and HuR-associated mechanism as shown for HDAC inhibitors. During 7-day culture growth assays, breast cancer cells exposed to growth-inhibiting concentrations of PS-341 (>1 nM) and LAQ824 (>5 nM) show at least additive growth suppression in combination as compared to their single agent activity. These findings suggest that proteasome and HDAC inhibitors may have clinical utility against breast cancers, especially those overexpressing ErbB2, thus warranting further preclinical evaluation of combined proteasome and HDAC inhibitor therapy.
Geographical variation and trends in outcomes of laparoscopic spleen-preserving distal pancreatectomy with or without splenic vessel preservation: A meta-analysis
Authors: Hua Yongfei, Ammar A. Javed, Richard Burkhart, Niek A. Peters, Alina Hasanain, Matthew J. Weiss, Christopher L. Wolfgang, Jin He
Journal: International Journal of Surgery (2017)
COMBI-MB: A phase II study of combination dabrafenib (D) and trametinib (T) in patients (pts) with <i>BRAF</i> V600–mutant (mut) melanoma brain metastases (MBM).
Authors: Michael A. Davies, Caroline Robert, Georgina V. Long, Jean Jacques Grob, Keith T. Flaherty, Ana Arance, Vanna Chiarion-Sileni, Luc Thomas, Thierry Lesimple, Laurent Mortier, Stergios J. Moschos, David Hogg, Ivan Marquez Rodas, Michele Del Vecchio, Celeste Lebbe, Nicolas Meyer, Ying Zhang, Yingjie Huang, Bijoyesh Mookerjee, Philippe Saiag
Journal: Journal of Clinical Oncology (2017)

9506 Background: CNS metastases are common and associated with very poor prognosis in pts with metastatic melanoma (MM). In the phase II BREAK-MB trial, D had clinical activity in BRAF V600–mut MBM. D + T has shown superiority over D alone in pts with BRAF V600–mut mm without MBM; however, efficacy of this regimen on MBM has not been characterized. Here, we report results from a phase II trial of D + T in BRAFV600–mut MBM (COMBI-MB; NCT02039947). Methods: This open-label, phase II study evaluated D 150 mg BID + T 2 mg QD in 4 MBM cohorts: (A) BRAFV600E, asymptomatic MBM, no prior local treatment (Tx); (B) BRAFV600E, asymptomatic MBM, prior local Tx; (C) BRAFV600D/K/R, asymptomatic MBM, with or without prior local Tx; and (D) BRAFV600D/E/K/R, symptomatic MBM, with or without prior local Tx. The primary objective was intracranial response rate (IRR) in cohort A (null hypothesis, IRR ≤ 35%). Secondary endpoints included IRR in cohorts B, C, and D; extracranial (ERR) and overall (ORR) response rates; intracranial (IDCR), extracranial (EDCR), and overall (ODCR) disease control rates; duration of IR, ER, and OR; PFS; OS; and safety. Results: 125 pts were enrolled (A, n = 76; B, n = 16; C, n = 16; D, n = 17). In cohort A, median age was 52, 53% were male, and 37% had LDH &gt; ULN. At data cutoff (28 Nov 2016; median f/u, 9.0 mo), in cohort A, investigator-assessed IRR was 58% (IDCR, 78%), ERR was 55% (EDCR, 80%), and ORR was 58% (ODCR, 80%). Median duration of IR, ER, and OR was 6.5 mo (95% CI, 4.9-10.3), 10.2 mo (95% CI, 6.5-13.0), and 6.5 mo (95% CI, 4.9-10.3), respectively. Median PFS was 5.6 mo (95% CI, 5.3-7.4). Independent review supported these results. 6-mo OS was 79%; with 31 pts (41%) still in f/u, preliminary median OS was 10.8 mo (95% CI, 8.7-19.6). Efficacy in cohorts B, C, and D will be reported. AEs across cohorts (any, 98%; grade 3/4, 48%) were consistent with prior D + T studies; 10% of pts (8% in cohort A) discontinued due to AEs. Conclusions: In this first report of a phase II trial evaluating a BRAF and MEK inhibitor combination in BRAFV600–mut MBM, the primary endpoint was met. Promising IRR and IDCR were seen with D + T, but responses appear less durable than reported for mm without MBMs. No unexpected safety issues were observed. Clinical trial information: NCT02039947.
Potential of Prospective Particle Therapy Trials to Increase the Therapeutic Ratio for Locally Advanced Lung Cancer
Authors: Charles R. Thomas
Journal: JAMA Oncology (2017)

Joe Y. Chang, MD, PhD; Vivek Verma, MD; Ming Li, MD; Wencheng Zhang, MD; Ritsuko Komaki, MD; Charles Lu, MD; Pamela K. Allen, PhD; Zhongxing Liao, MD; James Welsh, MD; Steven H. Lin, MD, PhD; Daniel Gomez, MD; Melenda Jeter, MD; Michael O'Reilly, MD; Ronald X. Zhu, PhD; Xiaodong Zhang, PhD; Heng Li, PhD; Radhe Mohan, PhD; John V. Heymach, MD, PhD; Ara A. Vaporciyan, MD; Stephen Hahn, MD; James D. Cox, MD
Abstract 289: Non-viral Rna Delivery To The Endothelium
Authors: daniel anderson
Journal: Circulation Research (2013)

Dysfunctional vasculature contributes to more disease than any other tissue in the body1. Small interfering RNAs (siRNAs) have the potential to help elucidate the role of endothelial cells in vivo by durably silencing multiple genes simultaneously, but this requires efficient delivery, which has remained challenging in cell types besides hepatocytes. We have developed nanoparticles that deliver siRNA to endothelial cells with high specificity, thereby facilitating the silencing of multiple endothelial cell genes in vivo. These particles do not significantly reduce gene expression in hepatocytes or immune cells even at doses forty times greater than those required for endothelial gene silencing. Optimized formulations achieved the most durable non-liver silencing reported to date, and delivered siRNAs that modified endothelial function in mouse models of vascular permeability, emphysema, primary tumor growth, and metastasis. We believe the nanomaterial described here may improve the ability to study endothelial gene function in vivo, and be used to treat diseases caused by vascular dysfunction.
The good and the bad collagens of fibrosis – Their role in signaling and organ function
Authors: M.A. Karsdal, S.H. Nielsen, D.J. Leeming, L.L. Langholm, M.J. Nielsen, T. Manon-Jensen, A. Siebuhr, N.S. Gudmann, S. Rønnow, J.M. Sand, S.J. Daniels, J.H. Mortensen, D. Schuppan
Journal: Advanced Drug Delivery Reviews (2017)
Modulation of Biomarker Expression by Osimertinib: Results of the Paired Tumor Biopsy Cohorts of the AURA Phase I Trial
Authors: Kenneth S. Thress, Vivien Jacobs, Helen K. Angell, James Chih-Hsin Yang, Lecia V. Sequist, Fiona Blackhall, Wu-Chou Su, Martin Schuler, Jürgen Wolf, Kathryn A. Gold, Mireille Cantarini, J. Carl Barrett, Pasi A. Jänne
Journal: Journal of Thoracic Oncology (2017)
Mechanically Tunable Bioink for 3D Bioprinting of Human Cells
Authors: Aurelien Forget, Andreas Blaeser, Florian Miessmer, Marius Köpf, Daniela F. Duarte Campos, Nicolas H. Voelcker, Anton Blencowe, Horst Fischer, V. Prasad Shastri
Journal: Advanced Healthcare Materials (2017)

Abstract This study introduces a thermogelling bioink based on carboxylated agarose (CA) for bioprinting of mechanically defined microenvironments mimicking natural tissues. In CA system, by adjusting the degree of carboxylation, the elastic modulus of printed gels can be tuned over several orders of magnitudes (5–230 Pa) while ensuring almost no change to the shear viscosity (10–17 mPa) of the bioink solution; thus enabling the fabrication of 3D structures made of different mechanical domains under identical printing parameters and low nozzle shear stress. Human mesenchymal stem cells printed using CA as a bioink show significantly higher survival (95%) in comparison to when printed using native agarose (62%), a commonly used thermogelling hydrogel for 3D‐bioprinting applications. This work paves the way toward the printing of complex tissue‐like structures composed of a range of mechanically discrete microdomains that could potentially reproduce natural mechanical aspects of functional tissues.
Risk and endocrine responsiveness (ER) categories in operated breast cancer (BC) patients (pts) from Tucuman, Argentina
Authors: S. Holgado, A. Elias de Vacaflor, M. Sanchez Segura, A. Viñuales, V. Audi, A. Raul, G. Vigo, R. Pedruzzi, J. J. Zarba
Journal: Journal of Clinical Oncology (2009)

e22224 Background: BC is the most common malignancy and the 1st cause of death by cancer in women in Tucuman, Argentina.The expression of hormone receptors and Her 2 neu in tumor tissue with other microscopic variables have shown to be indicators of prognosis and is also useful in therapeutic decisions.The molecular basis for treatment selection is actually the best way for a treatment “target” identification.The objective of this trial was to determine the patients profile in the population with BC under program (all pts studied under methodologic norms of a BC Detection Program) from Tucumán Argentina, defined by risk categories (high, intermediate or low) and endocrine response (high, incomplete or no response)according St Gallen 2007. Methods: The population included in the study were 246 pts with BC from public and private institutions in the province of Tucumán.HE routine biopsies were used for the assessment of histological type and subtype, tumor grade (according to Elston et al. and Nottinghan breast cancer grading method), axillary nodes status, tumor size, and the IHC staining for estrogen, progesterone receptors and Her2 neu.The results were studied grouping and evaluating the data for risk and endocrine responsiveness.The statistic applied was the exploratory analysis.IHC methods were validated with external and internal controls, in 7 cases Her2 was determined also by Fish. Results: 217/246 pts completed all parameters and were classified on risk categories: high (60 patients- 27,6%-); intermediate (156 patients-71,9%-) and low (1 patient-0,5%).No significant differences were found between the ages of groups with different levels of risk.The ER of the pts(n:242/246) showed highly endocrine responsive in 109/242 (45%), incompletely endocrine responsive in 49/242 (20,2%), endocrine no responsive 84/242 (34,7%). and association between endocrine levels of response and age range and tumor size (p &lt;0001 chi-square test and p&lt;0,017). Conclusions: These results are comparable with international data and allows us to know the patients profiles in our population under BC program. No significant financial relationships to disclose.