Malignant pleural effusion (MPE) is a common medical problem in lung cancer (LC). Pleural fluid cytology (PFC), chest computed tomography (CCT) and positron emission tomography (PET) findings are ...helpful as first line approach. The objectives of this study were to evaluate whether there is a correlation between PFC, CCT and PET in patients with MPE due to LC.
We selected patients from our electronic files. Data of PFC, pleural biopsy (PB), CCT and PET have been recorded and analyzed.
A total of 101 consecutive patients (66 males, 65.3%) with a mean age of 66.2±31 years were selected. Types of LC were adenocarcinoma in 71 patients (70.2%), squamous in 13 (12.8%), small-cell in 12 (11.8%) and large cell in 5 (4.9%). CCT showed nodules in 6 (5.9%), pleural thickening in 8 (7.9%) and both in 17 (16.8%) patients. PFC was positive in 55/91 thoracentesis (60.4%) and 32/52 thoracoscopy (61.5%), while PB in 38/40 performed (95%). PET fixation was found in 32/47 (68%) patients who had MPE at diagnosis. When we associate PFC to CCT and PET findings, the yield in our study becomes 90%. No correlation was observed between CCT findings and PFC (P=0.62) between PFC and PET fixation (P=0.63) or between CCT and PET (P=0.06).
In our cohort of LC patients with MPE, we observed a high sensitivity for PFC, while in most of the cases no findings were observed in CCT. PET had a relative low sensitivity. However, when all 3 methods were combined the yield was 90%.
Silicon carbide is an extremely hard, wear resistant, and thermally stable material with particular photoluminescence and interesting biocompatibility properties. For this reason, it is largely ...employed for industrial applications such as ceramics. More recently, nano-sized SiC particles were expected to enlarge their use in several fields such as composite supports, power electronics, biomaterials, etc. However, their large-scaled development is restricted by the potential toxicity of nanoparticles related to their manipulation and inhalation. This study aimed at synthesizing (by laser pyrolysis or sol–gel methods), characterizing physico-chemical properties of six samples of SiC nanopowders, then determining their in vitro biological impact(s). Using a macrophage cell line, toxicity was assessed in terms of cell membrane damage (LDH release), inflammatory effect (TNF-α production), and oxidative stress (reactive oxygen species generation). None of the six samples showed cytotoxicity while remarkable pro-oxidative reactions and inflammatory response were recorded, whose intensity appears related to the physico-chemical features of nano-sized SiC particles. In vitro data clearly showed an impact of the extent of nanoparticle surface area and the nature of crystalline phases (α-SiC vs. β-SiC) on the TNF-α production, a role of surface iron on free radical release, and of the oxidation state of the surface on cellular H
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The aim of this study was to develop a practical technique to detect mRNA expression and to validate a panel of mRNA markers for molecular differential diagnosis of renal cell carcinoma (RCC).
The ...renal cancer cell line SKRC-52 was used to set up the technique, which consisted of column extraction of RNA and one-step reverse transcription-PCR. We validated a panel of gene markers, including MN/CA9, cadherin-6, vimentin, mucin1, and parvalbumin, and studied 50 renal tumors (30 conventional, 9 papillary, and 5 chromophobe RCCs and 6 oncocytomas), 10 normal tissues, and 10 normal blood samples. We mimicked fine needle aspiration (FNA) biopsy in 10 kidneys with conventional RCC and applied this technique to 10 preoperative FNA samples from imaging-indeterminate renal tumors.
The technique could detect as few as 10 SKRC-52 cells with MN/CA9 as mRNA marker and was less time consuming and labor intensive. MN/CA9 was a sensitive and rather specific gene marker for conventional RCC. Cadherin-6 gene expression was a sensitive marker for conventional and papillary RCC. Vimentin was highly specific for conventional RCC. Mucin1 mRNA was sensitive for papillary and chromophobe RCC and oncocytoma. Parvalbumin mRNA was a sensitive and highly specific marker for both chromophobe RCC and oncocytoma. Thus, these mRNA markers represent the biomarker genes for the subtypes of renal tumors. Finally, we successfully applied the technique to FNA specimens. Five preoperative FNA samples were MN/CA9 gene positive, suggesting a RCC, whereas the routine cytology was positive in only three cases.
A rapid and sensitive assay of mRNA markers was developed for molecular differential diagnosis of RCC. This molecular assay can be used as a powerful ancillary to surgical pathological diagnosis and cytological diagnosis of RCC.
Abstract
Boehmite (γ-AlOOH) nanoparticles (NPs) are used in a wide range of industrial applications. However, little is known about their potential toxicity. This study aimed at a better ...understanding of the relationship between the physico-chemical properties of these NPs and their in vitro biological activity. After an extensive physico-chemical characterization, the cytotoxicity, pro-inflammatory response and oxidative stress induced by a bulk industrial powder and its ultrafine fraction were assessed using RAW264.7 macrophages. Although the bulk powder did not trigger a significant biological activity, pro-inflammatory response was highly enhanced with the ultrafine fraction. This observation was confirmed with boehmite NPs synthesized at the laboratory scale, with well-defined and tightly controlled physico-chemical features: toxicity was increased when NPs were dispersed. In conclusion, the agglomerates size of boehmite NPs has a major impact on their toxicity, highlighting the need to study not only raw industrial powders containing NPs but also the ultrafine fractions representative of respirable particles.
Abstract Purpose s: This study assesses the value of using Intraoperative Near Infrared Fluorescence Imaging and Indocyanine green to detect colorectal carcinomatosis during oncological surgery. In ...colorectal carcinomatosis cancer, two of the most important prognostic factors are completeness of staging and completeness of cytoreductive surgery. Presently, intraoperative assessment of tumoral margins relies on palpation and visual inspection. The recent introduction of Near Infrared fluorescence image guidance provides new opportunities for surgical roles, particularly in cancer surgery. Methods The study was a non-randomized, monocentric, pilot « ex vivo » blinded clinical trial validated by the ethical committee of University Hospital of Saint Etienne. Ten patients with colorectal carcinomatosis cancer scheduled for cytoreductive surgery were included. Patients received 0.25 mg/kg of Indocyanine green intravenously 24 hours before surgery. A Near Infrared camera was used to detect “ ex-vivo ” fluorescent lesions. Results There was no surgical mortality. Each analysis was done blindly. In a total of 88 lesions analyzed, 58 were classified by a pathologist as cancerous and 30 as non-cancerous. Among the 58 cancerous lesions, 42 were correctly classified by the Intraoperative Near-Infrared camera (sensitivity of 72.4%). Among the 30 non-cancerous lesions, 18 were correctly classified by the Intraoperative Near-Infrared camera (specificity of 60.0%). Conclusions Near Infrared fluorescence imaging is a promising technique for intraoperative tumor identification. It could help the surgeon to determine resection margins and reduce the risk of locoregional recurrence.
The relationship between particles’ physicochemical parameters, their uptake by cells and their degree of biological toxicity represent a crucial issue, especially for the development of new ...technologies such as fabrication of micro- and nanoparticles in the promising field of drug delivery systems. This work was aimed at developing a proof-of-concept for a novel model of double fluorescence submicronic particles that could be spotted inside phagolysosomes. Fluorescein isothiocyanate (FITC) particles were synthesized and then conjugated with a fluorescent pHrodo™ probe, red fluorescence of which increases in acidic conditions such as within lysosomes. After validation in acellular conditions by spectral analysis with confocal microscopy and dynamic light scattering, quantification of phagocytosis was conducted on a macrophage cell line in vitro. The biological impact of pHrodo functionalization (cytotoxicity, inflammatory response, and oxidative stress) was also investigated. Results validate the proof-of-concept of double fluorescent particles (FITC + pHrodo), allowing detection of entirely engulfed pHrodo particles (green and red labeling). Moreover incorporation of pHrodo had no major effects on cytotoxicity compared to particles without pHrodo, making them a powerful tool for micro- and nanotechnologies.
► TNF-α degradation in cell-free conditions. ► TNF-α adsorption on the walls of the wells in cell-free conditions. ► TNF-α adsorption on boehmite in cell-free conditions. ► Adsorption isotherms of ...TNF-α.
Biomolecules can be adsorbed on nanoparticles (NPs) and degraded during in vitro toxicity assays. These artifactual phenomena could lead to misinterpretation of biological activity, such as false-negative results. To avoid possible underestimation of cytokine release after contact between NP and cells, we propose a methodology to account for these artifactual phenomena and lead to accurate measurements. We focused on the pro-inflammatory cytokine tumor necrosis factor TNF-α. We studied well-characterized boehmite engineered NP aluminum oxide hydroxide, AlO(OH). The rate of TNF-α degradation and its adsorption (on boehmite and on the walls of wells) were determined in cell-free conditions by adding a known TNF-α concentration (1500pg/ml) under various experimental conditions. After a 24-h incubation, we quantified that 7wt.% of the initial TNF-α was degraded over time, 6wt.% adsorbed on the walls of 96-well plates, and 13wt.% adsorbed on the boehmite surface. Finally, boehmite NP were incubated with murine macrophages (RAW 264.7 cell line). The release of TNF-α was assessed for boehmite NP and the experimental data were corrected considering the artifactual phenomena, which accounted for about 20–30% of the total.
Nanoparticles (NP) physico-chemical features greatly influence NP/cell interactions. NP surface functionalization is often used to improve NP biocompatibility or to enhance cellular uptake. But in ...biological media, the formation of a protein corona adds a level of complexity. The aim of this study was to investigate in vitro the influence of NP surface functionalization on their cellular uptake and the biological response induced. 50nm fluorescent silica NP were functionalized either with amine or carboxylic groups, in presence or in absence of polyethylene glycol (PEG). NP were incubated with macrophages, cellular uptake and cellular response were assessed in terms of cytotoxicity, pro-inflammatory response and oxidative stress. The NP protein corona was also characterized by protein mass spectroscopy. Results showed that NP uptake was enhanced in absence of PEG, while NP adsorption at the cell membrane was fostered by an initial positively charged NP surface. NP toxicity was not correlated with NP uptake. NP surface functionalization also influenced the formation of the protein corona as the profile of protein binding differed among the NP types.
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•50nm silica nanoparticles (NP) were functionalized with NH2 or COOH groups±PEG.•NP were incubated with macrophages, NP uptake was enhanced in absence of PEG.•NP adsorption at the cell membrane was enhanced for positively charged NP.•Key role of chemical surface functionalization in NP/cell interactions•Key role of chemical surface functionalization in the protein corona formation
Objective. The aim of this study was to investigate the feasibility and future clinical applications of near-infrared (NIR) fluorescence imaging to guide liver resection surgery for metastatic cancer ...to improve resection margins. Summary Background Data. A subset of patients with metastatic hepatic tumors can be cured by surgery. The degree of long-term and disease-free survival is related to the quality of surgery, with the best resection defined as “R0” (complete removal of all tumor cells, as evidenced by microscopic examination of the margins). Although intraoperative ultrasonography can evaluate the surgical margins, surgeons need a new tool to perfect the surgical outcome. Methods. A preliminary study was performed on 3 patients. We used NIR imaging postoperatively “ex vivo” on the resected liver tissue. The liver tumors were preoperatively labelled by intravenously injecting the patient with indocyanine green (ICG), a NIR fluorescent agent (24 hours before surgery, 0.25 mg/kg). Fluorescent images were obtained using a miniaturized fluorescence imaging system (FluoStic, Fluoptics, Grenoble, France). Results. After liver resection, the surgical specimens from each patient were sliced into 10-mm sections in the operating room and analyzed with the FluoStic. All metastatic tumors presented rim-type fluorescence. Two specimens had incomplete rim fluorescence. The pathologist confirmed the presence of R1 margins (microscopic residual resection), even though the ultrasonographic analysis indicated that the result was R0. Conclusions. Surgical liver resection guided by NIR fluorescence can help detect potentially uncertain anatomical areas that may be missed by preoperative imaging and by ultrasonography during surgery. These preliminary results will need to be confirmed in a larger prospective patient series.
Immunocytochemistry may be of valuable help in typing most malignant serous effusions. Various preparatory methods are described including centrifugation and smearing, cytocentrifugation, cell blocks ...and liquid based cytology. The value and usefulness of immunocytochemistry depends on the experience of each pathologist. The use of a panel of antibodies associating markers of carcinomas with markers of mesothelial cells is recommended.
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