Relationship between background cancer pain, breakthrough pain, and analgesic treatment: a preliminary study for a better interpretation of epidemiological and clinical studies

Abstract Abstract Background: The different operational definitions of breakthrough cancer pain (BTcP) has generated unclear epidemiological data. Methods: A consecutive sample of patients was categorized on the basis of their background pain intensity, background analgesic treatment, and the presence of BTcP. Results: A total of 265 patients were surveyed; 117 patients had background pain and 91 patients presented peaks of pain intensity distinguishable from background pain. Of 117 patients with background pain, 49 patients were re-assessed after optimization of background analgesia (T1) within a mean of 8.2 days. Pain intensity significantly decreased in comparison with values recorded at admission (p\u2009<\u20090.0005); 75.5% of these patients had BTcP episodes, with a significant decrease in the number BTcP episodes in comparison with T0 (p\u2009<\u20090.0005). The mean BTcP intensity was significantly lower in comparison with T0 (p\u2009<\u20090.0005). Finally, the mean duration of untreated BTcP episodes decreased significantly in comparison with T0 (p\u2009=\u20090.016). After optimization of analgesic therapy, most patients with moderate or severe background pain receiving opioids for moderate pain, patients with moderate or severe pain receiving strong opioids, and patients with moderate or severe pain receiving no opioids moved to the group of patients with mild pain receiving strong opioids. The difference was significant (p\u2009=\u20090.022). Conclusion: Patients having good pain control after optimization of the analgesic regimen may have a decrease in number, intensity, and duration of BTcP, although the general prevalence of BTcP remains unchanged

Rapid Prototyping of 3D Biochips for Cell Motility Studies Using Two-Photon Polymerization

The study of cellular migration dynamics and strategies plays a relevant role in the understanding of both physiological and pathological processes. An important example could be the link between cancer cell motility and tumor evolution into metastatic stage. These strategies can be strongly influenced by the extracellular environment and the consequent mechanical constrains. In this framework, the possibility to study the behavior of single cells when subject to specific topological constraints could be an important tool in the hands of biologists. Two-photon polymerization is a sub-micrometric additive manufacturing technique that allows the fabrication of 3D structures in biocompatible resins, enabling the realization of ad hoc biochips for cell motility analyses, providing different types of mechanical stimuli. In our work, we present a new strategy for the realization of multilayer microfluidic lab-on-a-chip constructs for the study of cell motility which guarantees complete optical accessibility and the possibility to freely shape the migration area, to tailor it to the requirements of the specific cell type or experiment. The device includes a series of micro-constrictions that induce different types of mechanical stress on the cells during their migration. We show the realization of different possible geometries, in order to prove the versatility of the technique. As a proof of concept, we present the use of one of these devices for the study of the motility of murine neuronal cancer cells under high physical confinement, highlighting their peculiar migration mechanisms

Intermediate filaments ensure resiliency of single carcinoma cells, while active contractility of the actin cortex determines their invasive potential

During the epithelial-to-mesenchymal transition, the intracellular cytoskeleton undergoes severe reorganization which allows epithelial cells to transition into a motile mesenchymal phenotype. Among the different cytoskeletal elements, the intermediate filaments keratin (in epithelial cells) and vimentin (in mesenchymal cells) have been demonstrated to be useful and reliable histological markers. In this study, we assess the potential invasiveness of six human breast carcinoma cell lines and two mouse fibroblasts cells lines through single cell migration assays in confinement. We find that the keratin and vimentin networks behave mechanically the same when cells crawl through narrow channels and that vimentin protein expression does not strongly correlate to single cells invasiveness. Instead, we find that what determines successful migration through confining spaces is the ability of cells to mechanically switch from a substrate-dependent stress fibers based contractility to a substrate-independent cortical contractility, which is not linked to their tumor phenotype

Normal epithelial and triple-negative breast cancer cells show the same invasion potential in rigid spatial confinement

The extra-cellular microenvironment has a fundamental role in tumor growth and progression, strongly affecting the migration strategies adopted by single cancer cells during metastatic invasion. In this study, we use a novel microfluidic device to investigate the ability of mesenchymal and epithelial breast tumor cells to fluidize and migrate through narrowing microstructures upon chemoattractant stimulation. We compare the migration behavior of two mesenchymal breast cancer cell lines and one epithelial cell line, and find that the epithelial cells are able to migrate through the narrowest microconstrictions as the more invasive mesenchymal cells. In addition, we demonstrate that migration of epithelial cells through a highly compressive environment can occur in absence of a chemoattractive stimulus, thus evidencing that they are just as prone to react to mechanical cues as invasive cell

The X-Gamma Imaging Spectrometer (XGIS) onboard THESEUS

A compact and modular X and gamma-ray imaging spectrometer (XGIS) has been designed as one of the instruments foreseen on-board the THESEUS mission proposed in response to the ESA M5 call. The experiment envisages the use of CsI scintillator bars read out at both ends by single-cell 25 mm 2 Silicon Drift Detectors. Events absorbed in the Silicon layer (lower energy X rays) and events absorbed in the scintillator crystal (higher energy X rays and Gamma-rays) are discriminated using the on-board electronics. A coded mask provides imaging capabilities at low energies, thus allowing a compact and sensitive instrument in a wide energy band (~2 keV up to ~20 MeV). The instrument design, expected performance and the characterization performed on a series of laboratory prototypes are discussed.Comment: To be published in the Proceedings of the THESEUS Workshop 2017 (http://www.isdc.unige.ch/theseus/workshop2017.html), Journal of the Italian Astronomical Society (Mem.SAIt), Editors L. Amati, E. Bozzo, M. Della Valle, D. Gotz, P. O'Brien. Details on the THESEUS mission concept can be found in the white paper Amati et al. 2017 (arXiv:171004638) and Stratta et al. 2017 (arXiv:1712.08153

Identification and Characterization of BRCA1 and BRCA2 Founder Mutations

A large number of cancer predisposing BRCA1/BRCA2 mutations have been reported, with a wide variety among populations. In some restricted groups, specific germline mutations in these tumor suppressor genes have been found with high predominance, due to a founder effect. We focused our review on the Italian founder mutations. The first Italian BRCA1 founder mutation, 5083del19, was found in Calabria: the presence of common allele in all carriers of this mutation (also in families with Calabrian origin living in other parts of Italy) confirmed its founder effect. The same BRCA1 mutation was identified in the Sicilian population, but only the haplotype analysis can reveal the common ancestor of these groups. Another BRCA1 founder mutation, 4843delC, was found in Sicily. Four distinct BRCA1 mutations are attributable to families original from Tuscany: 3348delAG, 3285delA, 1499insA and 5183delTGT; the latter has been shown to be a founder mutation from North-Eastern Italy. The first BRCA2 mutation was identified in Sardinia, 8765delAG, a mutation already described as a founder mutation in Jewish-Yemenite families and also in French-Canadian population but with independent origins of carriers in these three populations. BRCA2 3951del3 and BRCA1 917delTT have been described as founder mutations in Middle Sardinia and in South and Middle Sardinia, respectively. Studies regarding prevalence and penetrance of founder mutations can allow to quantify the degree of homogeneity within a population and can surely help the geneticist and oncologist to simplify their choices in the genetic testing on high-risk families, on the basis of their ethnical origin

Characterization of timing and spacial resolution of novel TI-LGAD structures before and after irradiation

The characterization of spacial and timing resolution of the novel Trench Isolated LGAD (TI-LGAD) technology is presented. This technology has been developed at FBK with the goal of achieving 4D pixels, where an accurate position resolution is combined in a single device with the precise timing determination for Minimum Ionizing Particles (MIPs). In the TI-LGAD technology, the pixelated LGAD pads are separated by physical trenches etched in the silicon. This technology can reduce the interpixel dead area, mitigating the fill factor problem. The TI-RD50 production studied in this work is the first one of pixelated TI-LGADs. The characterization was performed using a scanning TCT setup with an infrared laser and a $^90$Sr source setup

timed flat infusion tfi 5 fluorouracil with irinotecan and oxaliplatin in pancreatic adenocarcinomas a single institution experience with fir fox regimen

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