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Due to their tunable surface plasmon and functional photothermal effects, gold nanorods (GNRs) have proved to be promising in a wide range of biomedical applications such as imaging, hyperthermia therapy and drug delivery. All these... more
Due to their tunable surface plasmon and functional photothermal effects, gold nanorods (GNRs) have proved to be promising in a wide range of biomedical applications such as imaging, hyperthermia therapy and drug delivery. All these applications can be controlled by the use of near infrared (NIR) light, which can penetrate deep into human tissues with minimal invasiveness. AuNRs thus hold the potential to combine both imaging diagnosis and therapeutic treatment into one single platform. Targeting of cancer cells by such devices can be carried out by three different strategies: 1) passive targeting based on the Enhanced Permeability and Retention (EPR) effect. Polyethylene glycol modified (PEGylated) GNRs tend to accumulate into tumors after intravenous injection much more than they do into normal tissue because of the leaky vasculature and the poor drainage of tumoral tissues; 2) active targeting which involves the immobilization of a selective ligand onto the surface of the GNRs; 3) the exploitation of cellular vehicles, i.e. cells that exhibit tropism to a lesion.
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Quantitative analysis of biomedical images, referred to as radiomics, is emerging as a promising approach to facilitate clinical decisions and improve patient stratification. The typical radiomic workflow includes image acquisition,... more
Quantitative analysis of biomedical images, referred to as radiomics, is emerging as a promising approach to facilitate clinical decisions and improve patient stratification. The typical radiomic workflow includes image acquisition, segmentation, feature extraction, and analysis of high-dimensional datasets. While procedures for primary radiomic analyses have been established in recent years, processing the resulting radiomic datasets remains a challenge due to the lack of specific tools for doing so. Here we present RadAR (Radiomics Analysis with R), a new software to perform comprehensive analysis of radiomic features. RadAR allows users to process radiomic datasets in their entirety, from data import to feature processing and visualization, and implements multiple statistical methods for analysis of these data. We used RadAR to analyze the radiomic profiles of more than 850 patients with cancer from publicly available datasets and showed that it was able to recapitulate expected results. These results demonstrate RadAR as a reliable and valuable tool for the radiomics community.Significance:A new computational tool performs comprehensive analysis of high-dimensional radiomic datasets, recapitulating expected results in the analysis of radiomic profiles of >850 patients with cancer from independent datasets.
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Supplementary Tables 1-2. STable 1: Table of the results of differential radiomic analysis between dead and alive patients from the Lung1 dataset (Aerts et al., 2014). STable 2: Table of the results of differential radiomic analysis... more
Supplementary Tables 1-2. STable 1: Table of the results of differential radiomic analysis between dead and alive patients from the Lung1 dataset (Aerts et al., 2014). STable 2: Table of the results of differential radiomic analysis across different disease stages for patients from the Lung1 dataset (Aerts et al., 2014).
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ABSTRACT Export Date: 13 May 2013, Source: Scopus
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Research Interests: Engineering, Pathology, Multispectral Imaging, Microscopy, Fluorescence, and 15 moreFluorescence Microscopy, Biology, Fluorescent Dyes and Reagents, Confocal Microscopy, Fluorescence Resonance Energy Transfer, Humans, Animals, Luminescence, Eukaryotic Cells, Lymph Node, Multispectral Images, GFP, Lymphatic System, Biochemistry and cell biology, and Autofluorescence
New light has recently been shed on the way phototherapy reduces bilirubin concentration in icteric infants. The introduction of a high-performance liquid chromatography technique led to the discovery of new photoisomers of bilirubin, the... more
New light has recently been shed on the way phototherapy reduces bilirubin concentration in icteric infants. The introduction of a high-performance liquid chromatography technique led to the discovery of new photoisomers of bilirubin, the configurational and structural isomers with high and low quantum yields, respectively, and to a renewed interest in the photochemical properties of bilirubin in vitro and in vivo. Circular dichroism and absorption spectroscopies have then shown that bilirubin behaves like a bichromophoric system, with the 2 halves of the molecule strongly interacting in the excited state. This coupling mechanism makes the quantum yields of bilirubin photochemistry wavelength-dependent, with marked effects in the long wavelength edge of the bilirubin absorption spectrum. The photochemistry of bilirubin is substantially similar in icteric rats and babies, and is consistent with what is observed in vitro. However, the metabolism of bilirubin photoproducts in rats sometimes differs quite significantly from that in babies. In particular, only the low quantum yield structural isomer, lumirubin, is efficiently excreted by babies. Although the relative role of the bilirubin photoprocesses in the therapy of hyperbilirubinemia is not yet known with certainty, the structural photoisomerization is generally assumed to represent the main route of bilirubin elimination. As a consequence, the determination of the spectral band that optimizes the process of formation of lumirubin in neonate may represent an important step in the improvement of the clinical protocol of phototherapy. Therefore, in addition to reviewing the most recent data on bilirubin photochemistry and the metabolism of bilirubin products, this article presents a computation of the optimal light for lumirubin formation. The combined effects of long-wavelength photochemistry of bilirubin and skin attenuation show that the optimal spectral range should be between 480 and 510 nm.
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Research Interests: Mathematics, Chemistry, Photochemistry, Phototherapy, Biological Sciences, and 15 morePhotoisomerization, Humans, Physical sciences, Quantum Efficiency, Bilirubin, CHEMICAL SCIENCES, Photochemistry and Photobiology, Irradiation, Isomerization, Laser Therapy, Molecular Conformation, Absorbance, Bovine Serum Albumin, Quantum Yield, and Isomerism
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Research Interests: Mathematics, Chemistry, Photochemistry, Fluorescence, Medicine, and 15 morePhototherapy, Biological Sciences, Photoisomerization, Humans, Physical sciences, Bilirubin, CHEMICAL SCIENCES, Photochemistry and Photobiology, Laser Therapy, Molecular Conformation, Absorbance, Bovine Serum Albumin, Monochromatic Color, Serum albumin, and Isomerism
Optical radiation sources, and in particular lasers, find an ever-increasing number of applications in the medical field. It is essential that personnel who are in the presence of an optical radiation source, whether operator, patient or... more
Optical radiation sources, and in particular lasers, find an ever-increasing number of applications in the medical field. It is essential that personnel who are in the presence of an optical radiation source, whether operator, patient or researcher, know precisely the risks inherent in the exposure of the human body to radiation. In order to reduce the risk of biological damage, beyond the provisions of the law on safety regulations, the precise information and accurate preparation of personnel are the main guarantee for the correct use of these sources. In all the application fields, the possibility of a biological damage cannot be completely eliminated, assuming the connotation of occupational risks. In order to understand the risks and operate their effective mitigation, the basic knowledge of the fundamental concepts at the basis of laser-matter interaction will be presented and discussed, with a focus on the physical parameters needed to efficiently estimate and mitigate the related occupational risks, in both a laboratory and clinical context.
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Cells exposed to light of appropriate wavelength show fluorescence emission in the UV-visible spectral range. This phenomenon, called natural fluorescence (NF), is related to cell compounds, i.e. proteins (1), nicotinic coenzymes (2),... more
Cells exposed to light of appropriate wavelength show fluorescence emission in the UV-visible spectral range. This phenomenon, called natural fluorescence (NF), is related to cell compounds, i.e. proteins (1), nicotinic coenzymes (2), flavins (3), etc., engaged in structural and metabolic processes. Thus a correlation does exist between NF emission and morpho-functional state of cells.
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We evaluate the combined usage of two systems, the Integral Quality Monitor (IQM) transmission detector and SoftDiso software, for in vivo dose monitoring by simultaneous detection of delivery and patient setup errors in whole breast... more
We evaluate the combined usage of two systems, the Integral Quality Monitor (IQM) transmission detector and SoftDiso software, for in vivo dose monitoring by simultaneous detection of delivery and patient setup errors in whole breast irradiation. An Alderson RANDO phantom was adapted with silicon breast prostheses to mimic the female anatomy. Plans with simulated delivery errors were created from a reference left breast plan, and patient setup errors were simulated by moving the phantom. Deviations from reference values recorded by both monitoring systems were measured for all plans and phantom positions. A 2D global gamma analysis was performed in SoftDiso for all phantom displacements. Both IQM signals and SoftDiso R-values are sensitive to small MU variations. However, only IQM is sensitive to jaw position variations. Conversely, IQM is unable to detect patient positioning errors, and the R-value has good sensitivity to phantom displacements. A gamma comparison analysis allows on...
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Bilirubin (BR), responsible for neonatal jaundice, is a 'Siamese twin' type of molecule containing two pyrromethenone chromophores conjoined by a saturated carbon CH2 group. Because neonatal jaundice is cured by phototheraphy,... more
Bilirubin (BR), responsible for neonatal jaundice, is a 'Siamese twin' type of molecule containing two pyrromethenone chromophores conjoined by a saturated carbon CH2 group. Because neonatal jaundice is cured by phototheraphy, bilirubin has been extensively studied by laser means. When the chromophores in each half of the molecule are identical, we have symmetrical BR (SBR); when they are not, we have antisymmetric BR (ASBR). The quantum yield of the photoproducts from SBR is not wavelength-dependent, while that from ASBR is, in organic solvents. Because of the proximity of the two chromophores, both the ASBR and SBR systems are subject to Davidov (dynamic electric dipole) splitting of the chromophore excited states. A quantum mechanical calculation shows that when the two (asymmetric) chromophore states are not degenerate, the higher Davidov state is preferentially occupied by the chromophore with the 'original' higher energy, and the lower Davidov state by the chro...
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In the framework of the increasing phenomenon of antibiotic-resistant infections, those caused by Helicobacter pylori (Hp) have a particular significance, being worldwide diffused and associated with severe pathologies, among which... more
In the framework of the increasing phenomenon of antibiotic-resistant infections, those caused by Helicobacter pylori (Hp) have a particular significance, being worldwide diffused and associated with severe pathologies, among which gastric cancer. To overcome antibiotic-resistance, we propose the use of photodynamic therapy (PDT), based upon cytotoxic species production following bacteria illumination with visible light. In the case of Hp infection, this is due to the presence of endogenous light absorbers (porphyrins). To perform intra-gastric PDT, we have recently designed an illuminating ingestible device equipped with LED sources, where a crucial parameter is the choice of the emission wavelengths optimizing Hp photo-killing. For this purpose, both porphyrin absorption peaks and optical penetration in tissues have to be carefully accounted. By merging data on Hp porphyrin absorption spectrum with those coming by a Monte-Carlo optical modelling for illumination of the stomach wall surface, we have calculated the relative Hp photo-killing efficacy in three representative tissue models in the 400-650nm range. Results indicate that in thicker models, the red wavelengths are ultimately more effective than the blue-shifted ones, due to the greater penetration length in tissues despite a minor porphyrin absorption.
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Helicobacter pylori gastric infections are among the most diffused worldwide, suffering from a rising rate of antibiotic resistance. In this context, some of the authors have previously designed an ingestible device in the form of a... more
Helicobacter pylori gastric infections are among the most diffused worldwide, suffering from a rising rate of antibiotic resistance. In this context, some of the authors have previously designed an ingestible device in the form of a luminous capsule to perform antibacterial photodynamic inactivation in the stomach. In this study, the light-emitting capsules were tested to verify the safety of use prior to perform clinical efficacy studies. First, laboratory tests measured the capsule temperature while in function and verified its chemical resistance in conditions mimicking the gastric and gut environments. Second, safety tests in a healthy minipig model were designed and completed, to verify both the capsule integrity and the absence of side effects, associated with its illumination and transit throughout the gastrointestinal tract. To this aim, a capsule administration protocol was defined considering a total of 6 animals with n = 2 treated with 8 capsules, n = 2 treated with 16 ca...
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ABSTRACT Gold nanorods (GNRs) are optimal contrast agents for near-infrared (NIR) laser-induced photothermal ablation of cancer. Selective targeting of cancer cells can be pursued by attaching specific molecules on the particles surface... more
ABSTRACT Gold nanorods (GNRs) are optimal contrast agents for near-infrared (NIR) laser-induced photothermal ablation of cancer. Selective targeting of cancer cells can be pursued by attaching specific molecules on the particles surface or by the use of cellular vectors loaded with GNRs. We performed and tested various targeting approaches by means of GNRs functionalization with (i) antibodies against Cancer-Antigen-125 (CA-125), (ii) inhibitors of the carbonic anhydrase 9 (CA9) and (iii) by the use of macrophages as cellular vectors. GNRs with a NIR absorption band at 810 nm were synthesized and PEGylated. For GNRs functionalization the targets of choice were CA-125, the most widely used biomarker for ovarian cancer, and CA9, overexpressed by hypoxic cells which are often located within the tumor mass. In the case of cellular vectors, to be used as Trojan horses naturally able to reach tumor areas, the surface of PEG-GNRs was modified to achieve unspecific interactions with macrophage membranes. In all cases the cellular uptake was evaluated by silver staining and cell viability was assessed by MTT test. Then tests of laser-induced GNRs-mediated hyperthermia were performed in various cell cultures illuminating with an 810 nm diode laser (CW, 0,5-4 W/cm2 power density, 1-10 min exposure time) and cell death was evaluated. Each targeting strategy we tested may be used alone or in combination, to maximize the tumor loading and therefore the efficiency of the laser treatment. Moreover, a multiple approach could help when the tumor variability interferes with the targeting directed to a single marker.