Gastrointestinal tumors: Phytochemical and drug combinations targeting the hallmarks of cancer

Cancer is a worldwide burden resulting in millions of deaths each year. In particular, gastrointestinal tumors are life-threatening malignancies and one of the leading reasons for death in developed countries. Phytochemicals can be found in grains, vegetables, fruits and several foods. Many phytochemicals, such as curcumin, genistein, luteolin, vitexin-2-O-xyloside, avenanthramides, quercetin, epigallocatechin-3-gallate (EGCG), resveratrol, sulforaphane, piperine and thymoquinone have been used in combination with different chemotherapeutic agents for their synergistic anticancer effects against various forms of cancer. In this review, we describe the antitumor properties and biological effects of combinations of phytochemicals and anticancer drugs against gastrointestinal tumors: colon cancer, gastric cancer, liver cancer, pancreatic cancer. We focus on the molecular pathways, oncoproteins and tumor suppressors modulated by the combination of phytochemicals with antitumor drugs and on the biomarkers of the hallmarks of cancer influenced by these therapeutic strategies in cancer cell lines, xenograft models and clinical trials. The increased knowledge of biomarkers and molecular pathways regulated by the combination of phytochemicals and conventional anticancer drugs in both in vitro and in vivo models will remarkably improve the efficacy of these therapeutic strategies against gastrointestinal tumors in future innovative clinical applications

Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren's contracture: a novel target for a possible future therapeutic strategy?

Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand causing fibrotic nodules and fascial cords which determine debilitating contracture and deformities of fingers and hands. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the pathogenesis, progression and recurrence of this disease, in order to find novel targets for alternative therapies and strategies in controlling DC. The expression of pro-inflammatory cytokines and of growth factors was detected by immunohistochemistry in fibrotic nodules and normal palmar fascia resected respectively from patients affected by DC and carpal tunnel syndrome (CTS; as negative controls). Reverse transcription (RT)-PCR analysis and immunofluorescence were performed to quantify the expression of transforming growth factor (TGF)-β1, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from Dupuytren's nodules. Histological analysis showed high cellularity and high proliferation rate in Dupuytren's tissue, together with the presence of myofibroblastic isotypes; immunohistochemical staining for macrophages was completely negative. In addition, a strong expression of TGF-β1, IL-1β and VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts and myofibroblasts in Dupuytren's nodular tissues, as compared with control tissues. These results were confirmed by RT-PCR and by immunofluorescence in pathological and normal primary cell cultures. These preliminary observations suggest that TGF-β1, IL-1β and VEGF may be considered potential therapeutic targets in the treatment of Dupuytren's disease (DD)

The HST Survey of BL Lac Objects: Gravitational Lens Candidates and Other Unusual Sources

We present HST observations of seven unusual objects from the HST ``snapshot survey'' of BL Lac objects, of which four are gravitational lens candidates. In three cases a double point sources is observed: 0033+595, with 1.58 arcsec separation, and 0502+675 and 1440+122, each with $\sim 0.3$ arcsec separation. The last two also show one or more galaxies, which could be either host or lensing galaxies. If any are confirmed as lenses, these BL Lac objects are excellent candidates for measuring H$_0$ via gravitational time delay because of their characteristic rapid, high amplitude variability. An additional advantage is that, like other blazars, they are likely superluminal radio sources, in which case the source plane is mapped out over a period of years, providing strong additional constraints on the lensing mass distribution. The fourth gravitational lens candidate is 1517+656, which is surrounded by three arclets forming an almost perfect ring of radius 2.4 arcsec. If this is indeed an Einstein ring, it is most likely a background source gravitationally lensed by the BL Lac object host galaxy and possibly a surrounding group or cluster. In the extreme case that all four candidates are true lenses, the derived frequency of gravitational lensing in this BL Lac sample would be an order of magnitude higher than in comparable quasar samples. We also report on three other remarkable BL Lac objects: 0138-097, which is surrounded by a large number of close companion galaxies; 0806+524, whose host galaxy contains an uncommon arc-like structure; and 1959+650, which is hosted by a gas rich elliptical galaxy with a prominent dust lane of $\sim 5\times 10^5 M_\odot$.Comment: 29 pages in total, 12 figure

HST Observations of the Host Galaxies of BL Lacertae Objects

Six BL Lac objects from the complete 1 Jy radio-selected sample of 34 objects were observed in Cycle 5 with the HST WFPC2 camera to an equivalent limiting flux of mu_I~26 mag/arcsec^2. Here we report results for the second half of this sample, as well as new results for the first three objects, discussed previously by Falomo et al. (1997). In addition, we have analyzed in the same way HST images of three X-ray-selected BL Lacs observed by Jannuzi et al. (1997). The ensemble of 9 BL Lac objects spans the redshift range from z=0.19 to ~1. Host galaxies are clearly detected in seven cases, while the other two, at z~0.258 (redshift highly uncertain) and z=0.997, are not resolved. The HST images constitute a homogeneous data set with unprecedented morphological information between a few tenths of an arcsecond and several arcseconds from the nucleus, allowing us in 6 of the 7 detected host galaxies to rule out definitively a pure disk light profile. The host galaxies are luminous ellipticals with an average absolute magnitude of M_I~-24.6 mag (with dispersion 0.7 mag), more than a magnitude brighter than L* and comparable to brightest cluster galaxies. The morphologies are generally smooth and have small ellipticities (epsilon<0.2). Given such roundness, there is no obvious alignment with the more linear radio structures. In the six cases for which we have HST WFPC2 images in two filters, the derived color profiles show no strong spatial gradients and are as expected for K-corrected passively evolving elliptical galaxies. The host galaxies of the radio-selected and X-ray-selected BL Lacs for this very limited sample are comparable in both morphology and luminosity.Comment: 23 pages, including 6 postscript figures and 3 tables (embedded). Latex requires aaspp4.sty and psfig.sty (not included). Accepted for publication in the Astrophysical Journa

Wide binaries as a critical test of Classical Gravity

Modified gravity scenarios where a change of regime appears at acceleration scales $a<a_{0}$ have been proposed. Since for $1 M_{\odot}$ systems the acceleration drops below $a_{0}$ at scales of around 7000 AU, a statistical survey of wide binaries with relative velocities and separations reaching $10^{4}$ AU and beyond should prove useful to the above debate. We apply the proposed test to the best currently available data. Results show a constant upper limit to the relative velocities in wide binaries which is independent of separation for over three orders of magnitude, in analogy with galactic flat rotation curves in the same $a<a_{0}$ acceleration regime. Our results are suggestive of a breakdown of Kepler's third law beyond $a \approx a_{0}$ scales, in accordance with generic predictions of modified gravity theories designed not to require any dark matter at galactic scales and beyond.Comment: accepted for publication in EPJ

Pullout strength of graphene and carbon nanotube/epoxy composites

An atomistic multiscale modelling approach is used to simulate the nonlinear pullout behaviour of interlinked single walled carbon nano tubes (SWCNT) and single layer graphene sheets (SLGS) embedded in an epoxy polymer. The pullout forces have been computed for various configurations of nanocomposites (SWCNT-SWCNT, SLGS-SLGS and hybrid SLGS-SWCNT), also by evaluating the effect provided by three different interlink compounds. The interfacial strength due to fibre pullout predicted by the hybrid atomistic-FE model is compared against experimental and molecular dynamics results available in open literature. The results show the specific deformation characteristics (localised auxetics) that provide an increase of pullout forces and interfacial strength with the use of the links

A Viewing Angle - Kinetic Luminosity Unification Scheme For BL Lacertae Objects

We propose a unified classification for BL Lac objects (BLs), focusing on the synchrotron peak frequency of the spectral energy distribution. The unification scheme is based on the angle Theta that describes the orientation of the relativistic jet and on the electron kinetic luminosity Lambda of the jet. We assume that Lambda scales with the size of the jet r in a self-similar fashion (Lambda propto r^2), as supported by observational data. The jets are self-similar in geometry and have the same pressure and median magnetic field at the inlet, independent of size. The self-similarity is broken for the highest energy electrons, which radiate mainly at high frequencies, since for large sources they suffer more severe radiative energy losses over a given fraction of the jet length. We calculate the optically thin synchrotron spectrum using an accelerating inner jet model based on simple relativistic gas dynamics and show that it can fit the observed infrared to X-ray spectrum of PKS 2155--304. We couple the accelerating jet model to the unification scheme and compare the results to complete samples of BLs. The negative apparent evolution of X-ray selected BLs is explained as a result of positive evolution of the jet electron kinetic luminosity $\Lambda_{kin}$. We review observational arguments in favor of the existence of scaled-down accretion disks and broad emission-line regions in BLs. The proposed unification scheme can explain the lack of observed broad emission lines in X-ray selected BLs, as well as the existence of those lines preferentially in luminous radio-selected BLs. Finally, we review observational arguments that suggest the extension of this unification scheme to all blazars.Comment: 32 pages, 8 figures, to be published in the ApJ (Oct 20, 1998

Congenital malformations potentially affecting respiratory function: Multidisciplinary approach and follow-up

Background and aim. Congenital malformations such as oesophageal atresia (OA) and tracheoe-sophageal fistula (TOF), congenital pulmonary airway malformations (CPAMs), congenital diaphragmatic hernia (CDH) and vascular rings (VRs) can affect lung development and respiratory function. This observa-tional study describes our multidisciplinary approach and respiratory follow-up of children with such congenital malformations. Methods. Clinical data of children followed at the Pediatric Respiratory Unit of Parma University Hospital (Italy) between January 2015 and January 2020 were collected. Results. Twenty-three patients with congenital malformation affecting lung development were identified. Almost half of our patients were diagnosed with fetal ultrasound. Children attended the clinic at a mean age of 3 (3.7) years and follow-up visits were scheduled every 6 months average. More than half of our patients were hospitalized for lower respiratory tract infections. Six out of 9 children able to perform spirometry showed anomalies in lung function. Chest physiotherapy was recommended especially in children with OA. Conclusions. Children with congenital malformations affecting lung development are at risk of short and long-term respiratory complications, especially in the first years of life. OA was the malformation more associated to respiratory problems. Multidisciplinary approach and appropriate personalized follow-up are recommended for the best management of these children. (www.actabiomedica.it)

ROXA: a new multi-frequency selected large sample of blazars with SDSS and 2dF optical spectroscopy

Context. Although Blazars are a small fraction of the overall AGN population they are expected to be the dominant population of extragalactic sources in the hard X-ray and gamma-ray bands and have been shown to be the largest contaminant of CMB fluctuation maps. So far the number of known blazars is of the order of several hundreds, but the forthcoming AGILE, GLAST and Planck space observatories will detect several thousand of objects of this type. Aims. In preparation for these missions it is necessary to identify new samples of blazars to study their multi-frequency characteristics and statistical properties. Methods. We compiled a sample of objects with blazar-like properties via a cross-correlation between large radio (NVSS, ATCAPMN) and X- ray surveys (RASS) using the SDSS-DR4 and 2dF survey data to spectroscopically identify our candidates and test the validity of the selection method. Results. We present the Radio - Optical - X-ray catalog built at ASDC (ROXA), a list of 816 objects among which 510 are confirmed blazars. Only 19% of the candidates turned out to be certainly non-blazars demonstrating the high efficiency of our selection method. Conclusions. Our catalog includes 173 new blazar identifications, or about 10% of all presently known blazars. The relatively high flux threshold in the X-ray energy band (given by the RASS survey) preferentially selects objects with high fx / fr ratio leading to the discovery of new High Energy Peaked BL Lac (HBLs). Our catalog therefore includes many new potential targets for GeV-TeV observations.Comment: 19 pages, 3 figure, 2 table