pinecone/core-2020-05-10-deduplication huggingface dataset:
The emerging role of exosome and microvesicle- (EMV-) based cancer therapeutics and immunotherapy

This document is the Accepted Manuscript version of the following article: Colin Moore, Uchini Kosgodage, Sigrun Lange, and Jameel M. Inal, ???The emerging role of exosome and microvesicle- (EMV-) based cancer therapeutics and immunotherapy???, International Journal of Cancer, Vol. 141 (3): 428-436, August 2017. DOI: https://doi.org/10.1002/ijc.30672. ?? 2017 UICC. This manuscript version may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.There is an urgent need to develop new combination therapies beyond existing surgery, radio- and chemo-therapy, perhaps initially combining chemotherapy with the targeting specificities of immunotherapy. For this, strategies to limit inflammation and immunosuppression and evasion in the tumour microenvironment are also needed. To devise effective new immunotherapies we must first understand tumour immunology, including the roles of T cells, macrophages, myeloid suppressor cells and of exosomes and microvesicles (EMVs) in promoting angiogenesis, tumour growth, drug resistance and metastasis. One promising cancer immunotherapy discussed uses cationic liposomes carrying tumour RNA (RNA-lipoplexes) to provoke a strong anti-viral-like (cytotoxic CD8+ ) anti-tumour immune response. Mesenchymal stem cell-derived EMVs, with their capacity to migrate towards inflammatory areas including solid tumours, have also been used. As tumour EMVs clearly exacerbate the tumour microenvironment, another therapy option could involve EMV removal. Affinity-based methods to deplete EMVs, including an immunodepletion, antibody-based affinity substrate, are therefore considered. Finally EMV and exosome-mimetic nanovesicles (NVs) delivery of siRNA or chemotherapeutic drugs that target tumours using peptide ligands for cognate receptors on the tumour cells are discussed. We also touch upon the reversal of drug efflux in EMVs from cancer cells which can sensitize cells to chemotherapy. The use of immunotherapy in combination with the advent of EMVs provides potent therapies to various cancers
Socioeconomic and demographic disparities in breast cancer stage at presentation and survival: A Swiss population-based study.

We explored socioeconomic and demographic disparities in breast cancer (BC) stage at presentation and survival in a Swiss population-based sample of female BC patients linked to the census-based Swiss National Cohort. Tumor stage was classified according to Surveillance, Epidemiology and End Results Program summary stage (in situ/localized/regional/distant). We used highest education level attained to estimate SEP (low/middle/high). Further demographic characteristics of interest were age at presentation (30-49/50-69/70-84 years), living in a canton with organized screening (yes/no), urbanity of residence (urban/peri-urban/rural), civil status (single/married/widowed/divorced) and nationality (Swiss/non-Swiss). We used ordered logistic regression models to analyze factors associated with BC stage at presentation and competing risk regression models for factors associated with survival. Odds of later-stage BC were significantly increased for low SEP women (odds ratio 1.19, 95%CI 1.06-1.34) compared to women of high SEP. Further, women living in a canton without organized screening program, women diagnosed outside the targeted screening age and single/widowed/divorced women were more often diagnosed at later stages. Women of low SEP experienced an increased risk of dying from BC (sub-hazard ratio 1.22, 95%CI 1.05-1.43) compared to women of high SEP. Notably, these survival inequalities could not be explained by socioeconomic differences in stage at presentation and/or other sociodemographic factors. It is concerning that these social gradients have been observed in a country with universal health insurance coverage, high health expenditures and one of the highest life expectancies in the world
Dietary fiber intake and head and neck cancer risk: A pooled analysis in the International Head and Neck Cancer Epidemiology consortium.

The possible role of dietary fiber in the etiology of head neck cancers (HNCs) is unclear. We used individual-level pooled data from ten case-control studies (5959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium, to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Odds Ratios (ORs) and their 95% Confidence Intervals (CIs) were estimated using unconditional multiple logistic regression applied to quintile categories of non-alcohol energy-adjusted fiber intake and adjusted for tobacco and alcohol use and other known or putative confounders. Fiber intake was inversely associated with oral and pharyngeal cancer combined (OR for 5th vs. 1st quintile category = 0.49, 95% CI: 0.40-0.59; p for trend &lt;0.001) and with laryngeal cancer (OR = 0.66, 95% CI: 0.54-0.82, p for trend &lt;0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral and pharyngeal cancer combined. Nonetheless, inverse associations were consistently observed for the subsites of oral and pharyngeal cancers and within most strata of the considered covariates, for both cancer sites. Our findings from a multicenter large-scale pooled analysis suggest that, although in the presence of between-study heterogeneity, a greater intake of fiber may lower HNC risk
The human PKP2/plakophilin-2 gene is induced by Wnt/β-catenin in normal and colon cancer-associated fibroblasts

Colorectal cancer results from the malignant transformation of colonic epithelial cells. Stromal fibroblasts are the main component of the tumour microenvironment, and play an important role in the progression of this and other neoplasias. Wnt/β-catenin signalling is essential for colon homeostasis, but aberrant, constitutive activation of this pathway is a hallmark of colorectal cancer. Here we present the first transcriptomic study on the effect of a Wnt factor on human colonic myofibroblasts. Wnt3A regulates the expression of 1,136 genes, of which 662 are upregulated and 474 are downregulated in CCD-18Co cells. A set of genes encoding inhibitors of the Wnt/β-catenin pathway stand out among those induced by Wnt3A, which suggests that there is a feedback inhibitory mechanism. We also show that the PKP2 gene encoding the desmosomal protein Plakophilin-2 is a novel direct transcriptional target of Wnt/β-catenin in normal and colon cancer-associated fibroblasts. PKP2 is induced by β-catenin/TCF through three binding sites in the gene promoter and one additional binding site located in an enhancer 20 kb upstream from the transcription start site. Moreover, Plakophilin-2 antagonizes Wnt/β-catenin transcriptional activity in HEK-293T cells, which suggests that it may act as an intracellular inhibitor of the Wnt/β-catenin pathway. Our results demonstrate that stromal fibroblasts respond to canonical Wnt signalling and that Plakophilin-2 plays a role in the feedback control of this effect suggesting that the response to Wnt factors in the stroma may modulate Wnt activity in the tumour cells.Grant sponsor: Consejería de Educación, Juventud y Deporte, Comunidad de Madrid; Grant number: S2010/BMD-2344 Colomics2; Grant
sponsor: Spanish Ministerio de Economía y Competitividad-Fondos FEDER; Grant numbers: Nurcamein SAF-2015-71878-REDT, SAF2013-
43468-R, SAF2014-53819-R; Grant sponsor: Instituto de la Salud Carlos III - Fondos FEDER; Grant number: CB16/12/00273 CIBERONC,
RD12/0036/0021; Grant sponsor: Agencia Estatal de Investigación - Fondos FEDER; Grant number: SAF2016-76377-
Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations.

Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-Trøndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n = 626; HUNT2 n = 112; median follow-up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D2and 25(OH)D3combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend = 0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant
Etiology of hormone receptor positive breast cancer differs by levels of histologic grade and proliferation

Limited epidemiological evidence suggests that the etiology of hormone receptor positive (HR+) breast cancer may differ by levels of histologic grade and proliferation. We pooled risk factor and pathology data on 5,905 HR+ breast cancer cases and 26,281 controls from 11 epidemiological studies. Proliferation was determined by centralized automated measures of KI67 in tissue microarrays. Odds ratios (OR), 95% confidence intervals (CI) and p-values for case-case and case-control comparisons for risk factors in relation to levels of grade and quartiles (Q1-Q4) of KI67 were estimated using polytomous logistic regression models. Case-case comparisons showed associations between nulliparity and high KI67 [OR (95% CI) for Q4 vs. Q1=1.54 (1.22, 1.95)]; obesity and high grade [grade 3 vs. 1=1.68 (1.31, 2.16)] and current use of combined hormone therapy (HT) and low grade [grade 3 vs. 1=0.27 (0.16, 0.44)] tumors. In case-control comparisons, nulliparity was associated with elevated risk of tumors with high but not low levels of proliferation [1.43 (1.14, 1.81) for KI67 Q4 vs. 0.83 (0.60, 1.14) for KI67 Q1]; obesity among women ≥50 years with high but not low grade tumors [1.55 (1.17, 2.06) for grade 3 vs. 0.88 (0.66, 1.16) for grade 1] and HT with low but not high grade tumors [3.07 (2.22, 4.23) for grade 1 vs. 0.85 (0.55, 1.30) for grade 3]. Menarcheal age and family history were similarly associated with HR+ tumors of different grade or KI67 levels. These findings provide insights into the etiologic heterogeneity of HR+ tumors
A clinicopathological study and prognostic factor analysis of 177 salivary duct carcinoma patients from The Netherlands

Salivary duct carcinoma (SDC) is a subtype of salivary gland cancer with a dismal prognosis and a need for better prognostication and novel treatments. The aim of this national cohort study was to investigate clinical outcome, prognostic factors, androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) expression. SDC patients diagnosed between 1990 and 2014 were identified by the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA). Subsequently, medical records were evaluated and pathological diagnoses reviewed. Data were analyzed for overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and prognostic factors. AR was evaluated by immunohistochemistry (IHC), HER2 by IHC and fluorescent in-situ hybridization. A total of 177 patients were included. The median age was 65 years, 75% were male. At diagnosis, 68% presented with lymph node metastases and 6% with distant metastases. Median OS, DFS and DMFS were 51, 23 and 26 months, respectively. In patients presenting without distant metastases, the absolute number of positive lymph nodes was associated with poor OS and DMFS in a multivariable analysis. AR and HER2 were positive in 161/168 (96%) and 44/153 (29%) tumors, respectively, and were not prognostic factors. SDC has a dismal prognosis with primary lymph node involvement in the majority of patients. The absolute number of lymph node metastases was found to be the only prognostic factor for DMFS and OS. AR expression and-to a lesser extent-HER2 expression hold promise for systemic treatment in the metastatic and eventually adjuvant setting
Quantifying the Stacking Registry Matching in Layered Materials

A detailed account of a recently developed method [Marom et al., Phys. Rev.
Lett. 105, 046801 (2010)] to quantify the registry mismatch in layered
materials is presented. The registry index, which was originally defined for
planar hexagonal boron-nitride, is extended to treat graphitic systems and
generalized to describe multi-layered nanotubes. It is shown that using simple
geometric considerations it is possible to capture the complex physical
features of interlayer sliding in layered materials. The intuitive nature of
the presented model and the efficiency of the related computations suggest that
the method can be used as a powerful characterization tool for interlayer
interactions in complex layered systems.Comment: 8 pages, 8 figures. To be published in a special issue of the Israel
  Journal of Chemistry regarding "Inorganic Nanotubes and Nanostructures
Attaching different kinds of proteinaceous nanospheres to a variety of fabrics using ultrasound radiation

The application of a rapid, non-destructive, cost-effective technique such as ultrasonic emulsification for the coating of different textiles was explored. The technical benefits for this research were the generation of multifunctional materials and their combinations through environmentally friendly processing technologies. We have shown for the first time that ultrasonic waves can be used to coat proteinaceous micro- and nanospheres (PM) of BSA (Bovine Serum Albumin) protein and casein on the surface of cotton and polyester (PE) fabrics. The creation and the anchoring of the microbubbles to the fabrics were performed by a one step reaction, and the process is usually stopped after 3 min. The PM of bovine serum albumin (BSA) bonded to cotton and polyester fabrics has shown stability for ~9 months. The PMs were shown to be attached more strongly to the polyester than to the cotton, and sustained stronger washing conditions on PE. The diameter of the BSA and the casein spheres on cotton was in the range of 0.8–1.0 µm, while on the PE it varied between 60 and 120 nm.This research, was carried out as part of the activities of the LIDWINE Consortium, Contract No NMP2-CT-2006-026741 LIDWINE is an IP Project of the 6<SUP>th</SUP> EC Progra
Supramolecular Assemblies Constructed by Cucurbituril-Catalyzed Click Reaction

Cataloged from PDF version of article.Cucurbituril homologues are multi-functional macrocycles that can find applications in many areas and have numerous interesting features setting them apart from the other macrocycles. Among them, the ability of one of the cucurbituril homologues, cucurbit[6]uril (CB6), to catalyze 1,3-dipolar cycloaddition in a regiospecific fashion is truly exceptional. Using this feature, small molecules can be clicked together to form complex structures in a very efficient way. Accordingly, in this article we review recent research involving the use of CB6-catalyzed 1,3-dipolar cycloaddition or the click reaction of CB6 in the construction of supramolecular assemblies including rotaxanes, pseudorotaxanes, polyrotaxanes, polypseudorotaxanes, molecular switches, machines, and nanovalves
Quantum control landscape for a $\Lambda$-atom in the vicinity of second
  order traps

We show that the second order traps in the control landscape for a
three-level $\Lambda$-system found in our previous work {\it Phys. Rev. Lett.}
{\bf 106}, 120402 (2011) are not local maxima: there exist directions in the
space of controls in which the objective grows. The growth of the objective is
slow --- at best 4th order for weak variations of the control. This implies
that simple gradient methods would be problematic in the vicinity of second
order traps, where more sophisticated algorithms that exploit the higher order
derivative information are necessary to climb up the control landscape
efficiently. The theory is supported by a numerical investigation of the
landscape in the vicinity of the $\varepsilon(t)=0$ second order trap,
performed using the GRAPE and BFGS algorithms
Topical Developments in High-Field Dynamic Nuclear Polarization

We report our recent efforts directed at improving high-field dynamic nuclear polarization (DNP) experiments. We investigated a series of thiourea nitroxide radicals and the associated DNP enhancements ranging from ε=25 to 82, which demonstrate the impact of molecular structure on performance. We directly polarized low-gamma nuclei, including [superscript 13]C, [superscript 2]H, and [superscript 17]O, by the cross effect mechanism using trityl radicals as a polarization agent. We discuss a variety of sample preparation techniques for DNP with emphasis on the benefits of methods that do not use a glass-forming cryoprotecting matrix. Lastly, we describe a corrugated waveguide for use in a 700 MHz/460 GHz DNP system that improves microwave delivery and increases enhancements up to 50%.National Institutes of Health (U.S.) (Grant EB002804)National Institutes of Health (U.S.) (Grant EB003151)National Institutes of Health (U.S.) (Grant EB002026)National Institutes of Health (U.S.) (Grant EB001960)National Institutes of Health (U.S.) (Grant EB001035)National Institutes of Health (U.S.) (Grant EB001965)National Institutes of Health (U.S.) (Grant EB004866)National Institute of General Medical Sciences (U.S.) (Grant GM095843)Natural Sciences and Engineering Research Council of Canada (Postdoctoral Fellowship
The Development of Visible‐Light Photoredox Catalysis in Flow

Visible‐light photoredox catalysis has recently emerged as a viable alternative for radical reactions otherwise carried out with tin and boron reagents. It has been recognized that by merging photoredox catalysis with flow chemistry, slow reaction times, lower yields, and safety concerns may be obviated. While flow reactors have been successfully applied to reactions carried out with UV light, only recent developments have demonstrated the same potential of flow reactors for the improvement of visible‐light‐mediated reactions. This review examines the initial and continuing development of visible‐light‐mediated photoredox flow chemistry by exemplifying the benefits of flow chemistry compared with conventional batch techniques
Thermoelectric materials: A brief historical survey from metal junctions and inorganic semiconductors to organic polymers

The use of thermoelectric technology is attractive in many potential applications, such as energy scavenging from waste heat. The basic principles for harvesting electricity from a temperature gradient were first discovered around 180 years ago, but the contemporary technology utilising inorganic semiconductors was only developed since the early 1950s. The widespread use of this platform has so far been limited by a combination of relatively low efficiency in energy conversion or by issues related to the utilisation of rare, expensive and/or toxic elements that can be difficult to process. Recently much interest has been focused on the use of organic materials in thermoelectric devices, prompted by the possibility of developing large-area, low-cost devices. Considerable research in the last 20 years has been focused on understanding and improving organic thermoelectric properties, with remarkable progress recently published for compounds such as PEDOT and others. Here we provide an overview into thermoelectricity, from the initial discoveries made by Johann Seebeck to modern practical applications including the current trends in organic thermoelectric research. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.We are grateful to the EPSRC Doctoral Training Centre in Plastic Electronics (grant number EP/G037515/1) for fundin
Selenium in Diketopyrrolopyrrole-based Polymers: Influence on Electronic Properties and Charge Carrier Mobilities

Cataloged from PDF version of article.Diketopyrrolopyrrole (DPP)-based pi-conjugated copolymers with thiophene have exceptionally high electron mobilities. This paper investigates electronic properties and charge carrier mobilities of selenophene containing analogues. Two new copolymers, with alternating thiophene DPP (TDPP) and selenophene DPP (SeDPP) units, were synthesized. Two side-chains, hexyl (Hex) and triethylene glycol (TEG) were employed, yielding polymers designated as PTDPPSeDPP-Hex and PTDPPSeDPP-TEG. Selenophene systems have smaller band gaps, with concomitant enhancement of the stability of the reduced state. For both polymers, ambipolar mobilities were observed in organic field-effect transistors (OFET). Grazing incidence X-ray diffraction (GIXD) data indicates preferential edge-on orientation of PTDPPSeDPP-TEG, which leads to superior charge transport properties of the TEG substituted polymer, as compared to its Hex analogue. Time-dependent-density functional theory (TDDFT) calculations corroborate the decrease in the optical band gap with the inclusion of selenophene. Ambipolar charge transport is rationalized by exceptionally wide conduction bands. Delta SCF calculations confirm the larger electron affinity, and therefore the greater stability, of the reduced form of the selenophene-containing DPP polymer in presence of chloroform
Protein Needles as Molecular Templates for Artificial Metalloenzymes

Construction of artificial metalloenzymes based on protein assemblies is a promising strategy for the development of new catalysts, because the three-dimensional nanostructures of proteins with defined individual sizes can be used as molecular platforms that allow the arrangement of catalytic active centers on their surfaces. Protein needles/tubes/fibers are suitable for supporting various functional molecules, including metal complexes, synthetic molecules, metal nanoparticles, and enzymes with high densities and precise locations. Compared with bulk systems, the protein tube- and fiber-based materials have higher activities for catalytic reactions and electron transfer, as well as enhanced functions when used in electronic devices. The natural and synthetic protein tubes and fibers are constructed by self-assembly of monomer proteins or peptides. For more precise designs of arrangements of metal complexes, we have developed a new conceptual framework, based on the isolation of a robust needle structure from the cell-puncturing domains of a bacteriophage. The artificial protein needle shows great promise for use in creating efficient catalytic systems by providing the means to arrange the locations of various metal complexes on the protein surface. In this account, we discuss the recent development of protein needle-based metalloenzymes, and the future developments we are anticipating in this field