tbuckley/cabot-search huggingface dataset:
Induced fluorescence of breast cancer in the mouse model: A simple technology to improve visualization of malignant tissue during breast cancer surgery
Authors: A. D. Chan, G. A. Luiken, M. M. Quigley, M. Xu, R. M. Hoffman
Journal: Journal of Clinical Oncology (2006)

10557 Background: Accurate identification of all malignant tissue at the time of lumpectomy or mastectomy can at times be challenging. When positive margins are discovered, significant additional time and effort may be required by the surgeon to complete the initial procedure. Inducing the cancer cells to be fluorescent offers the potential to improve the surgeon’s ability to rapidly and accurately identify and excise the malignant tissue at the time of surgery. We have previously demonstrated the feasibility of inducing tumor fluorescence with fluorophore-tagged anti-tumor antigen antibodies using a human colon cancer cell line. We present here our recent results using a human breast cancer cell line in the nude mouse. Methods: A human breast cancer cell line, MDA-MB-468 known to express CA 15–3 was used. Breast cancer cells were subcutaneously implanted in 14 nude mice. Three to five weeks after injection, tumor nodules were easily visible and palpable. Using the tail vein method, mice were injected with fluorophore-tagged anti-CA 15–3 and were examined using a small animal imaging system with a 470 nm light source. Mice were also examined using a simple blue LED flashlight fitted with a fixed 470 nm band-pass filter and were observed through filtered goggles. Results: Tumor nodules could be seen to fluoresce through the skin when illuminated with a 470 nm light source. When tumor nodules were exposed and examined with white light, the nodules could be seen but when illuminated with the 470 nm light source, tumor fluorescence allowed clear identification of nearby small tumor nodules and clear identification of tumor margins easily distinguishable from the normal tissue. Conclusions: For this technology to work, tumor antigens must be known and antibodies to these antigens available. It is easy to perform, requires no complex equipment or operator expertise and could be easily adapted to surgical oncology in any hospital setting. It has the potential to improve surgical accuracy in women undergoing initial lumpectomy or mastectomy as well as axillary lymph node dissection or sentinel node biopsy. In addition it could aid in the surgery of patients undergoing resection of isolated recurrent hepatic or pulmonary metastases. No significant financial relationships to disclose.
Risk and Consequences of Atrial Fibrillation
Authors: Mintu P. Turakhia
Journal: JAMA Cardiology (2017)

Shang-Hung Chang, MD, PhD; Chang-Fu Kuo, MD, PhD; I-Jun Chou, MD; Lai-Chu See, PhD; Kuang-Hui Yu, MD; Shue-Fen Luo, MD; Lu-Hsiang Huang, MS; Weiya Zhang, PhD; Michael Doherty, MD; Ming-Shien Wen, MD; Chi-Tai Kuo, MD; Yung-Hsin Yeh, MD
Measuring the <i>Plasmodium falciparum</i> HRP2 protein in blood from artesunate-treated malaria patients predicts post-artesunate delayed hemolysis
Authors: Papa Alioune Ndour, Sébastien Larréché, Oussama Mouri, Nicolas Argy, Frédérick Gay, Camille Roussel, Stéphane Jauréguiberry, Claire Perillaud, Dominique Langui, Sylvestre Biligui, Nathalie Chartrel, Audrey Mérens, Eric Kendjo, Aniruddha Ghose, Md. Mahtab Uddin Hassan, Md. Amir Hossain, Hugh W. F. Kingston, Katherine Plewes, Arjen M. Dondorp, Martin Danis, Sandrine Houzé, Serge Bonnefoy, Marc Thellier, Charles J. Woodrow, Pierre A. Buffet
Journal: Science Translational Medicine (2017)

Artesunate, the recommended drug for severe malaria, rapidly clears the malaria parasite from infected patients but frequently induces anemia-called post-artesunate delayed hemolysis (PADH)-for which a simple predictive test is urgently needed. The underlying event in PADH is the expulsion of artesunate-exposed parasites from their host erythrocytes by pitting. We show that the histidine-rich protein 2 (HRP2) of the malaria parasite Plasmodium falciparum persists in the circulation of artesunate-treated malaria patients in Bangladesh and in French travelers who became infected with malaria in Africa. HRP2 persisted in whole blood (not plasma) of artesunate-treated patients with malaria at higher levels compared to quinine-treated patients. Using an optimized membrane permeabilization method, HRP2 was observed by immunofluorescence, Western blotting, and electron microscopy to persist in once-infected red blood cells from artesunate-treated malaria patients. HRP2 was deposited at the membrane of once-infected red blood cells in a pattern similar to that for ring erythrocyte surface antigen (RESA), a parasite invasion marker. On the basis of these observations, we developed a semiquantitative titration method using a widely available HRP2-based rapid diagnostic dipstick test. Positivity on this test using a 1:500 dilution of whole blood from artesunate-treated patients with malaria collected shortly after parasite clearance predicted subsequent PADH with 89% sensitivity and 73% specificity. These results suggest that adapting an existing HRP2-based rapid diagnostic dipstick test may enable prediction of PADH several days before it occurs in artesunate-treated patients with malaria.
The Effect of Helicobacter Pylori Outer Membrane Vesicles On Vacuolation in Gastric and Colonic Epithelial Cells
Authors: EM Mullaney, AM Terres, DP Kelleher
Journal: Endoscopy (2006)

Aims: Helicobacter pylori constitutively sheds small outer membrane vesicles (OMVs) in vivo. OMVs provide a vehicle for the delivery of virulence factors to the gastric mucosa and are known to contain the vacuolating cytotoxin VacA. To compare the vacuolating effect of H. pylori OMVs on AGS cells and T84 monolayers using the neutral red assay.
Abstract P406: N-3 Fatty Acids Measured in Saliva do not Reflect Short-term Changes in Intake but may be Associated with Medium or Long-term Intake
Authors: Ana Baylin, Hannia Campos, Constanza Marin, Luz Nayibe Vargas, Mercedes Mora-Plaza, Eduardo Villamor
Journal: Circulation (2013)

Background: N-3 fatty acids in blood are adequate biomarkers of intake compared to dietary questionnaires because they do not rely on memory or self-reported information, and are not subject to interviewer bias. However, obtaining blood samples is an invasive approach, particularly among children. Measuring fatty acids in saliva is a non-invasive alternative that has not been explored yet in detail in population studies. Objective: To evaluate if n-3 fatty acids measured in saliva would be adequate biomarkers of intake. Methods: We selected 60 families for a 4-week intervention trial among participants in the Bogotá School Children Cohort. They were randomly assigned to receive a month’s supply of either soybean oil (high in α-linolenic acid [ALA], n=30) or sunflower oil (low in ALA, n=30). We obtained saliva and finger-prick blood samples in the children at baseline and follow-up. Fatty acids were analyzed by gas liquid chromatography in saliva and blood. To measure short-term responsiveness, we compared means of ALA in saliva by intervention arm at follow-up. To assess validity, we compared n-3 fatty acids concentrations in saliva and blood at baseline with the use of Spearman correlation coefficients. Results: Mean (SD) age of study participants was 14.5 (1.5) years; 37% (22 of 60) were male. Treatment groups did not differ at baseline with regard to socio-demographic and anthropometric characteristics, or fatty acids levels. Children assigned to soybean oil had a non-statistically significantly higher mean (SD) ALA concentration in saliva at follow-up (0.62 [0.66]), compared to children assigned to sunflower oil (0.47 [0.44]; p=0.45). Follow-up concentrations of long-chain n-3 fatty acids (EPA and DHA) in saliva did not differ significantly between intervention arms. To assess validity, we compared saliva and blood fatty acids concentrations at baseline (n=60) and found significant correlations for ALA (r=0.44, p=0.0005), EPA (r=0.27, p=0.04), and DHA (r=0.34, p=0.008). Conclusions: N-3 fatty acids measured in saliva do not reflect accurately short-term changes in ALA intake. However, moderate correlations between n-3 fatty acids in saliva and blood suggest that measuring fatty acids in saliva may be a valid proxy for intake. It is possible that fatty acids in saliva may have a slower turnover than those in blood and could be better biomarkers for medium or long-term intake of n-3 fatty acids.
Multi-gene panel testing of patients with multiple primary malignancies suspected with hereditary cancer syndrome.
Authors: Gloria HJ Chan, Pei Yi Ong, Jeffrey JH Low, Hwai L. Kong, Samuel Guan Wei Ow, David SP Tan, Yi Wan Lim, Lim Siew Eng, Soo Chin Lee
Journal: Journal of Clinical Oncology (2017)

1512 Background: Developing multiple primary cancers is an indicator of underlying hereditary cancer predisposition, but there is a paucity of data regarding the characteristics and clinical genetic testing outcome of these patients. Methods: We compared cancer index patients with 1 vs &gt; 1 primary malignancy who underwent evaluation and clinical testing with multi-gene panels comprising up to 49 genes in a cancer genetics clinic in a tertiary cancer centre in Asia from 1998-2016. Results: Among 1191 cancer index patients, 960 (80.6%), 205 (17.2%), and 26 (2.2%) respectively had 1, 2, and ≥3 primary malignancies. Among patients with &gt; 1 primary cancers (n = 231), the most common cancer pairs were breast-breast (35.4%), breast-ovary (12.1%), endometrium-ovary (8.2%), colon-colon (2.4%) and, colon-endometrium (2.4%). The mean age at diagnosis of the first, second and third cancers were 46.0 (21 to 87), 52.1 (21 to 89) and 57.7 (41 to 83) respectively. The mean duration between first and second cancers is 6.0 years (0 to 32). The most commonly suspected syndromes in patients with 1 vs &gt; 1 primary cancer were hereditary breast and ovarian cancer 63.8% vs 53.6%, Lynch 24.8% vs 31.1%, Li-Fraumeni syndromes 1.8% vs 1.7%, and others 9.3% vs 13.4% (p = 0.03). Patients with &gt; 1 primary cancer were more likely to have &gt; 20% a priori risk of suspected hereditary cancer syndrome (42.8% vs. 26.5%; p &lt; 0.001). 504/1191 (42.3%) patients underwent gene testing, including 394/960 (41.0%) and 110/231 (47.6%) patients with 1 vs &gt; 1 cancer. Deleterious mutations were more likely to be identified in patients with &gt; 1 vs 1 cancer (34.5% vs. 25.8%; p = 0.073), with causative genes being BRCA1 38.5%, BRCA2 17.9%, MLH1/MSH2/MSH6 20.5%, TP53 7.7%, and others (ATM [n = 2], MUTYH, APC, PALB2, RAD51 [n = 1 each]) for patients with &gt; 1 cancer. VUS rates were 31.7% vs.31.8% in patients with 1 vs &gt; 1 cancer, and were identified in genes including BRIP1, CHEK2, PALLD, POLE, PTEN, STK11, SMARCA4, and VHL. Conclusions: Patients with &gt; 1 primary cancer comprised one-fifth of cancer index patients evaluated at a cancer genetics clinic, and were more likely to be found with deleterious mutations than patients with only 1 cancer on multi-gene panel testing.
A<sub>3</sub> Adenosine Receptors as Modulators of Inflammation: From Medicinal Chemistry to Therapy
Authors: Kenneth A. Jacobson, Stefania Merighi, Katia Varani, Pier Andrea Borea, Stefania Baraldi, Mojgan Aghazadeh Tabrizi, Romeo Romagnoli, Pier Giovanni Baraldi, Antonella Ciancetta, Dilip K. Tosh, Zhan‐Guo Gao, Stefania Gessi
Journal: Medicinal Research Reviews (2017)

Abstract The A 3 adenosine receptor (A 3 AR) subtype is a novel, promising therapeutic target for inflammatory diseases, such as rheumatoid arthritis (RA) and psoriasis, as well as liver cancer. A 3 AR is coupled to inhibition of adenylyl cyclase and regulation of mitogen‐activated protein kinase (MAPK) pathways, leading to modulation of transcription. Furthermore, A 3 AR affects functions of almost all immune cells and the proliferation of cancer cells. Numerous A 3 AR agonists, partial agonists, antagonists, and allosteric modulators have been reported, and their structure–activity relationships (SARs) have been studied culminating in the development of potent and selective molecules with drug‐like characteristics. The efficacy of nucleoside agonists may be suppressed to produce antagonists, by structural modification of the ribose moiety. Diverse classes of heterocycles have been discovered as selective A 3 AR blockers, although with large species differences. Thus, as a result of intense basic research efforts, the outlook for development of A 3 AR modulators for human therapeutics is encouraging. Two prototypical selective agonists, N6‐(3‐Iodobenzyl)adenosine‐5′‐N‐methyluronamide (IB‐MECA; CF101) and 2‐chloro‐N6‐(3‐iodobenzyl)‐adenosine‐5′‐N‐methyluronamide (Cl‐IB‐MECA; CF102), have progressed to advanced clinical trials. They were found safe and well tolerated in all preclinical and human clinical studies and showed promising results, particularly in psoriasis and RA, where the A 3 AR is both a promising therapeutic target and a biologically predictive marker, suggesting a personalized medicine approach. Targeting the A 3 AR may pave the way for safe and efficacious treatments for patient populations affected by inflammatory diseases, cancer, and other conditions.
Localised delivery of doxorubicin to prostate cancer cells through a PSMA-targeted hyperbranched polymer theranostic
Authors: Amanda K. Pearce, Joshua D. Simpson, Nicholas L. Fletcher, Zachary H. Houston, Adrian V. Fuchs, Pamela J. Russell, Andrew K. Whittaker, Kristofer J. Thurecht
Journal: Biomaterials (2017)
Erratum: Molecular study of malignant gliomas treated with epidermal growth factor receptor inhibitors: Tissue analysis from North American Brain Tumor Consortium Trials 01-03 and 00-01 (Clinical Cancer Research (November 1, 2005) 11 (7841-7850))
Authors: Jeffrey J. Raizer, A. B. Lassman, M. R. Rossi
Journal: Clinical Cancer Research (2006)
Economic Evaluation of Carfilzomib+Dexamethasone (Kd) Vs Bortezomib+Dexamethasone (Vd) in Relapsed or Refractory Multiple Myeloma (R/RMM)
Authors: Andrzej Jakubowiak, Istvan Matyas Majer, Ivan Houisse, Agnes Benedict, Marco Campioni, Sumeet Panjabi, Sikander Ailawadhi
Journal: Blood (2016)
Immunotherapy of Prostate Cancer: Facts and Hopes
Authors: Marijo Bilusic, Ravi A. Madan, James L. Gulley
Journal: Clinical Cancer Research (2017)

In the last few years, immunotherapy has become an important cancer treatment modality, and although the principles of immunotherapy have evolved over many decades, the FDA approvals of sipuleucel-T and ipilimumab began a new wave in immuno-oncology. Despite the current enthusiasm, it is unlikely that any of the immunotherapeutics alone can dramatically change prostate cancer outcomes, but combination strategies are more promising and provide a reason for optimism. Several completed and ongoing studies have shown that the combination of cancer vaccines or checkpoint inhibitors with different immunotherapeutic agents, hormonal therapy (enzalutamide), radiotherapy (radium 223), DNA-damaging agents (olaparib), or chemotherapy (docetaxel) can enhance immune responses and induce more dramatic, long-lasting clinical responses without significant toxicity. The goal of prostate cancer immunotherapy does not have to be complete eradication of advanced disease but rather the return to an immunologic equilibrium with an indolent disease state. In addition to determining the optimal combination of treatment regimens, efforts are also ongoing to discover biomarkers of immune response. With such concerted efforts, the future of immunotherapy in prostate cancer looks brighter than ever. Clin Cancer Res; 23(22); 6764-70. ©2017 AACR.
Increased Affinity for RNA Targets Evolved Early in Animal and Plant Dicer Lineages through Different Structural Mechanisms
Authors: Haiyan Jia, Oralia Kolaczkowski, James Rolland, Bryan Kolaczkowski
Journal: Molecular Biology and Evolution (2017)

Understanding the structural basis for evolutionary changes in protein function is central to molecular evolutionary biology and can help determine the extent to which functional convergence occurs through similar or different structural mechanisms. Here, we combine ancestral sequence reconstruction with functional characterization and structural modeling to directly examine the evolution of sequence-structure-function across the early differentiation of animal and plant Dicer/DCL proteins, which perform the first molecular step in RNA interference by identifying target RNAs and processing them into short interfering products. We found that ancestral Dicer/DCL proteins evolved similar increases in RNA target affinities as they diverged independently in animal and plant lineages. In both cases, increases in RNA target affinities were associated with sequence changes that anchored the RNA's 5′phosphate, but the structural bases for 5′phosphate recognition were different in animal versus plant lineages. These results highlight how molecular-functional evolutionary convergence can derive from the evolution of unique protein structures implementing similar biochemical mechanisms.
Sixty seconds on . . . the CEP
Authors: Anne Gulland
Journal: BMJ (2017)

You know, the CEP. Close friend of the STP, the IFR, and the RTT. It’s the capped expenditure process—another lovely phrase straight from the NHS Acronym Referral Site for England (ARSE).

According to a letter sent to trusts and clinical commissioning groups in Cheshire, it’s a …
Rape survivor is sentenced to 30 years in jail under El Salvador’s extreme anti-abortion law
Authors: Ingrid Torjesen
Journal: BMJ (2017)

A 19 year old who became pregnant after being raped has been sentenced to 30 years in prison on charges of “aggravated homicide” after experiencing obstetric complications delivering the baby.

A court in El Salvador, which has some of the world’s strictest abortion laws, sentenced Evelyn Beatriz Hernandez Cruz on 5 July after prosecutors argued that in April the teenager had aborted the fetus and thrown its remains into a …
Prenatal Nitrate Exposure and Childhood Asthma. Influence of Maternal Prenatal Stress and Fetal Sex
Authors: Sonali Bose, Yueh-Hsiu Mathilda Chiu, Hsiao-Hsien Leon Hsu, Qian Di, Maria José Rosa, Alison Lee, Itai Kloog, Ander Wilson, Joel Schwartz, Robert O. Wright, Sheldon Cohen, Brent A. Coull, Rosalind J. Wright
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Impact of ambient pollution upon children's asthma may differ by sex, and exposure dose and timing. Psychosocial stress can also modify pollutant effects. These associations have not been examined for in utero ambient nitrate exposure.
Heat-Related Mortality in Japan after the 2011 Fukushima Disaster: An Analysis of Potential Influence of Reduced Electricity Consumption
Authors: Yoonhee Kim, Antonio Gasparrini, Masahiro Hashizume, Yasushi Honda, Chris Fook Sheng Ng, Ben Armstrong
Journal: Environmental Health Perspectives (2017)

Background: In March 2011, the Great East Japan Earthquake devastated several power stations and caused severe electricity shortages. This accident was followed by the implementation of policies to reduce summer electricity consumption in the affected areas, for example, by limiting air-conditioning (AC) use. This provided a natural experimental scenario to investigate if these policies were associated with an increase in heat-related mortality. Objectives: We examined whether the reduced electricity consumption in warm season modified heat-related mortality from 2008 to 2012. Methods: We conducted prefecture-specific interrupted time-series (ITS) analyses to compare temperature–mortality associations before and after the earthquake, and used meta-analysis to generate combined effect estimates for the most affected and less affected areas (prefectures with >10% or ≤10% reductions in electricity consumption, respectively). We then examined whether the temperature–mortality association in Tokyo, one of the most affected areas, was modified by the percent reduction in electricity consumption relative to expected consumption for comparable days before the earthquake. Results: Contrary to expectations, we estimated a 5–9% reduction in all-cause heat-related mortality after the earthquake in the 15 prefectures with the greatest reduction in electricity consumption, and little change in the other prefectures. However, the percent reduction in observed vs. expected daily electricity consumption after the earthquake did not significantly modify daily heat-related mortality in Tokyo. Conclusions: In the prefectures with the greatest reductions in electricity consumption, heat-related mortality decreased rather than increased following the Great East Japan Earthquake. Additional research is needed to determine whether this finding holds for other populations and regions, and to clarify its implications for policies to reduce the consequences of climate change on health. https://doi.org/10.1289/EHP493
Doctors can allow terminally ill baby to die after parents’ appeal to European court fails
Authors: Clare Dyer
Journal: BMJ (2017)

A couple who raised £1.3m (€1.47m; $1.67m) to take their terminally ill baby for experimental treatment in the US have had their last hopes dashed by the European Court of Human Rights.

The court in Strasbourg, France, was the final recourse for Charlie Gard’s parents after the UK courts ruled that the treatment would be futile and that he should be …
Pharmacokinetics and Pharmacodynamics-Based Mathematical Modeling Identifies an Optimal Protocol for Metronomic Chemotherapy
Authors: Joseph Ciccolini, Dominique Barbolosi, Christophe Meille, Aurélie Lombard, Cindy Serdjebi, Sarah Giacometti, Laetitia Padovani, Eddy Pasquier, Nicolas André
Journal: Cancer Research (2017)

Metronomic chemotherapy is usually associated with better tolerance than conventional chemotherapy, and encouraging response rates have been reported in various settings. However, clinical development of metronomic chemotherapy has been hampered by a number of limitations, including the vagueness of its definition and the resulting empiricism in protocol design. In this study, we developed a pharmacokinetic/pharmacodynamic mathematical model that identifies in silico the most effective administration schedule for gemcitabine monotherapy. This model is based upon four biological assumptions regarding the mechanisms of action of metronomic chemotherapy, resulting in a set of 6 minimally parameterized differential equations. Simulations identified daily 0.5-1 mg/kg gemcitabine as an optimal protocol to maximize antitumor efficacy. Both metronomic protocols (0.5 and 1 mg/kg/day for 28 days) were evaluated in chemoresistant neuroblastoma-bearing mice and compared with the standard MTD protocol (100 mg/kg once a week for 4 weeks). Systemic exposure to gemcitabine was 14 times lower in the metronomic groups compared with the standard group. Despite this, metronomic gemcitabine significantly inhibited tumor angiogenesis and reduced tumor perfusion and inflammation in vivo, while standard gemcitabine did not. Furthermore, metronomic gemcitabine yielded a 40%-50% decrease in tumor mass at the end of treatment as compared with control mice (P = 0.002; ANOVA on ranks with Dunn test), while standard gemcitabine failed to significantly reduce tumor growth. Stable disease was maintained in the metronomic groups for up to 2 months after treatment completion (67%-72% reduction in tumor growth at study conclusion, P < 0.001; ANOVA on ranks with Dunn test). Collectively, our results confirmed the superiority of metronomic protocols in chemoresistant tumors in vivoCancer Res; 77(17); 4723-33. ©2017 AACR.