Evolution of bone metastases in patients receiving at least three months of checkpoint inhibitors.

BACKGROUND: To investigate the evolution of bone metastases in patients receiving immune checkpoint inhibitors (ICI). METHODS: A single-center retrospective study included cancer patients with bone metastases treated with ICI at our institution between January 2014 and September 2019. Clinical and biological data were collected from medical records and independent expert review of imaging was performed. Target and non-target lesions were identified and followed up to 1 year. Patients were then classified as bone responder or non-responder. Comparisons between groups were performed with Student's t test or Mann-Whitney test. RESULTS: Among 1108 patients screened, 192 patients had bone metastases and 48 patients were included in the final analysis, with lung cancer, renal carcinoma and melanoma as most represented cancer type. Half of the patients experienced stability, condensation or peripheral sclerosis of bone lesions. Initial progression before stabilization with or without sclerosis of bone lesion occurred for 19% of patients (pseudoprogression). There was an association between bone response and global oncological outcomes. Bone responder patients had a significant decrease in morphine and co-analgesic prescription as well as a significant decrease in alkaline phosphatases compared to non-responder patients. CONCLUSION: Bone response was observed in half of patients with available imaging and follow-up after 3 months of ICI treatment, with sclerosis observed in one-third of bone lesions at month 3, in all tumor types. Up to 20% of patients experienced a pseudoprogression of bone lesions such as previously described in primary tumor and other metastatic sites. Bone response was associated with improvement of pain and survival.

In vitro study of carbon black nanoparticles on human pulmonary artery endothelial cells: effects on calcium signaling and mitochondrial alterations.

Human exposure to manufactured nanoparticles (NPs) is a public health concern. Endothelial cells lining the inner surface of arteries could be one of the primary targets for inhaled nanoparticles. Moreover, it is well known that alteration in calcium signaling is a critical event involved in the physiopathology of cardiovascular diseases. The objective of this study was to assess the role of oxidative stress in carbon black FW2 NPs-induced alteration in calcium signaling and mitochondria in human pulmonary artery endothelial cells. To this end, cells were exposed for 4 or 24 h to FW2 NPs (1-10 µg/cm2) and the following endpoints were studied: (i) production of ROS by fluorimetry and electron paramagnetic resonance, (ii) variation in intracellular calcium concentration by confocal microscopy, and (iii) mitochondrial alteration and apoptosis by confocal microscopy and transmission electronic microscopy. Exposure to FW2 NPs concentration-dependently increases oxidative stress, evidenced by the production of superoxide anion leading to an alteration in calcium content of intracellular organelles, such as endoplasmic reticulum and mitochondria activating, in turn, intrinsic apoptosis. This study provides evidence that FW2 NPs exposure impairs calcium signaling and mitochondria triggered by oxidative stress, and, thus, could act as a cardiovascular disease risk owing to the key role of calcium homeostasis in the control of vascular tone.

Protective properties of Avène Thermal Spring Water on biomechanical, ultrastructural and clinical parameters of human skin.

BACKGROUND: Thermal Spring Water (TSW) has been recognized to have beneficial effects on skin; however, the mechanisms underlying these are not completely elucidated. AIMS: We compared the effects of Avène TSW with mineral-rich (MR) TSW on the biomechanical properties of the skin using mechanistic ex vivo assays and clinical studies. METHODS: Ex vivo studies included the effect of both TSWs on the structure of the surface of human skin explants using scanning electron microscopy (SEM); mineral elemental content on the skin surface using SEM coupled to energy dispersing X-ray spectroscopy; and the stress properties of the stratum corneum (SC) when exposed to dehydration. Human clinical studies were conducted to compare the soothing effect of TSWs after a dermatological chemical peeling of face skin and to evaluate the overall sensitive scale of consumers using Avène TSW for 7 days. RESULTS: Both TSWs preserved surface skin ultrastructure; however, crystals formed from MR-TSW were needle-like and formed small grains, present in clusters heterogeneously spread over the surface. Needle crystals were mainly composed of calcium, while small clusters were mainly composed of sulphur. By contrast, Avène TSW-formed crystals composed of sodium and chlorine only were regular in shape and homogeneously distributed across the skin surface. Peak stress of SC layers was increased by MR-TSW, whereas Avène TSW showed a comparatively reduced effect on dehydration and stress. The difference in the two TSW types was reflected in clinical findings comparing postpeeling redness after TSW application. Avène TSW significantly decreased postpeeling redness, while MR-TSW increased it. The overall sensitive scale of consumers was decreased by 47% using Avène TSW for 7 days. CONCLUSIONS: Avène TSW decreases postpeeling redness and soothes sensitive skin in human volunteers. Mechanistic studies suggested that differences in biomechanical effects could be linked to differences in calcium content of the TSW.

CEP-stabilized, sub-18 fs, 10 kHz and TW-class 1 kHz dual output Ti:Sa laser with wavelength tunability option.

Generating energetic, few-cycle laser pulses with stabilized carrier-envelope phase at a high-repetition rate constitutes a first step to access the ultra-fast dynamics underlying the interaction of matter with intense, ultrashort pulses in attosecond science or high-field physics. We present here a Ti:Sa-based 1 kHz TW-class laser delivering 17.8 fs pulses with 350 mrad shot-to-shot CEP noise based on an original 10 kHz front-end design. In parallel to this short pulse duration operation mode, it is possible to tune the output wavelength of the front end within a 90 nm range around 800 nm.

A new HPF specimen carrier adapter for the use of high-pressure freezing with cryoscanning electron microscope: two applications: stearic acid organization in a hydroxypropyl methylcellulose matrix and mice myocardium.

Cryogenic transmission electron microscopy of high-pressure freezing (HPF) samples is a well-established technique for the analysis of liquid containing specimens. This technique enables observation without removing water or other volatile components. The HPF technique is less used in scanning electron microscopy (SEM) due to the lack of a suitable HPF specimen carrier adapter. The traditional SEM cryotransfer system (PP3000T Quorum Laughton, East Sussex, UK; Alto Gatan, Pleasanton, CA, USA) usually uses nitrogen slush. Unfortunately, and unlike HPF, nitrogen slush produces water crystal artefacts. So, we propose a new HPF specimen carrier adapter for sample transfer from HPF system to cryogenic-scanning electronic microscope (Cryo-SEM). The new transfer system is validated using technical two applications, a stearic acid in hydroxypropyl methylcellulose solution and mice myocardium. Preservation of samples is suitable in both cases. Cryo-SEM examination of HPF samples enables a good correlation between acid stearic liquid concentration and acid stearic occupation surface (only for homogeneous solution). For biological samples as myocardium, cytoplasmic structures of cardiomyocyte are easily recognized with adequate preservation of organelle contacts and inner cell organization. We expect this new HPF specimen carrier adapter would enable more SEM-studies using HPF.

Adaptation of two groups of Oenococcus oeni strains to red and white wines: the role of acidity and phenolic compounds.

AIMS: Oenococcus oeni is the lactic acid bacteria species which is the most adapted to wine. Recently, two groups of strains that form two genetic lineages were described in red and white Burgundy wines. The aim of this study was to analyse the phenotypes of these strains in order to determine how they have adapted specifically to either red or white wine. METHODS AND RESULTS: Four strains from each group were tested in grape must and in wines to evaluate their tolerance to pH and to phenolic compound content. White wine strains proved to be the most tolerant to low pH, both in grape must and in wine, whereas they were inhibited by the presence of grape tannins in wine. Red wine strains were more sensitive to acidity, but very resistant to phenolic compounds. CONCLUSIONS: The results suggest that pH and phenolic compounds drive strain selection at several stages of wine production. SIGNIFICANCE AND IMPACT OF THE STUDY: Although it is well known that O. oeni is well adapted to wine, this study shows that strains of some genetic lineages within this species have evolved to adapt better than others to specific types of wines.

Original Ti:Sa 10 kHz front-end design delivering 17 fs, 170 mrad CEP stabilized pulses up to 5 W.

We present a compact 10 kHz Ti:Sa front end relying on an original double-crystal regenerative amplifier design. This new configuration optimizes the thermal heat load management, allowing the production of a 110 nm large spectrum and maintaining a good beam profile quality. The front end delivers up to 5 W after compression, 17 fs pulses with a 170 mrad shot-to-shot residual carrier-envelope phase noise.

A review: what is the spermosphere and how can it be studied?

The spermosphere is the zone surrounding seeds where interactions between the soil, microbial communities and germinating seeds take place. The concept of the spermosphere is usually only applied during germination sensu stricto. Despite the transient nature of this very small zone of soil around the germinating seed, the microbial activities which occur there may have long-lasting impacts on plants. The spermosphere is indirectly characterized by either (i) seed exudates, which could be inhibitors or stimulators of micro-organism growth or (ii) the composition of the microbiome on and around the germinating seeds. The microbial communities present in the spermosphere directly reflect that of the germination medium or are host-dependent and influenced quantitatively and qualitatively by host exudates. Despite its strong impact on the future development of plants, the spermosphere remains little studied. This can be explained by the technical difficulties related to characterizing this concept due to its short duration, small size and biomass, and the number and complexity of the interactions that take place. However, recent technical methods, such as metabolite profiling, combining phenotypic methods with DNA- and RNA-based methods, could be used to investigate seed exudates, microbial communities and their interactions with the soil environment.

Effects of FW2 Nanoparticles Toxicity in a New In Vitro Pulmonary Vascular Cells Model Mimicking Endothelial Dysfunction.

Several epidemiological studies have revealed the involvement of nanoparticles (NPs) in respiratory and cardiovascular mortality. In this work, the focus will be on the effect of manufactured carbon black NPs for risk assessment of consumers and workers, as human exposure is likely to increase. Since the pulmonary circulation could be one of the primary targets of inhaled NPs, patients suffering from pulmonary hypertension (PH) could be a population at risk. To compare the toxic effect of carbon black NPs in the pulmonary circulation under physiologic and pathological conditions, we developed a new in vitro model mimicking the endothelial dysfunction and vascular dynamics observed in vascular pathology such as PH. Human pulmonary artery endothelial cells were cultured under physiological conditions (static and normoxia 21% O2) or under pathological conditions (20% cycle stretch and hypoxia 1% O2). Then, cells were treated for 4 or 6 h with carbon black FW2 NPs from 5 to 10 µg/cm2. Different endpoints were studied: (i) NPs internalization by transmission electronic microscopy; (ii) oxidative stress by CM-H2DCFDA probe and electron paramagnetic resonance; (iii) NO (nitrites and nitrates) production by Griess reaction; (iv) inflammation by ELISA assay; and (v) calcium signaling by confocal microscopy. The present study characterizes the in vitro model mimicking endothelial dysfunction in PH and indicates that, under such pathological conditions, oxidative stress and inflammation are increased along with calcium signaling alterations, as compared to the physiological conditions. Human exposure to carbon black NPs could produce greater deleterious effects in vulnerable patients suffering from cardiovascular diseases.

[Positron emission tomography using 18F-fluorodeoxyglucose in the management of nonsmall cell lung cancers in 2006]. / La tomographie par émission de positons au 18fluorodésoxyglucose (18FDG-TEP) dans la prise en charge du cancer bronchique non à petites cellules en 2006.

Technological progress and numerous published studies allow to estimate the best place of the 18F-fluorodeoxyglucose positron emission tomography, a real functional metabolic imagery, in the clinical and therapeutic strategy of non small cell lung cancers.

Pools of cadmium in Chlamydomonas reinhardtii revealed by chemical imaging and XAS spectroscopy.

The green micro-alga Chlamydomonas reinhardtii is commonly used as a model to investigate metallic stress in photosynthetic organisms. The aim of this study was to explore processes implemented by three C. reinhardtii strains to cope with cadmium (Cd), and particularly to evidence Cd sequestration in the cell. For that, we used a combination of subcellular fractionation and chemical imaging (micro X-ray fluorescence (µXRF) and transmission electron microscopy (TEM/X-EDS)) to identify subcellular compartments of Cd accumulation, and X-ray absorption spectroscopy (XAS) to determine chemical Cd speciation. C. reinhardtii wild type strain 11/32b (wt), a newly design strain (pcs1) expressing a modified phytochelatin synthase in the chloroplast and a cell wall less strain CC400 (cw15) were exposed to 70 µM Cd. At this Cd concentration, cell vitality was not affected, however, the strains showed various strategies to cope with Cd stress. In wt, most of Cd was diffused in the whole cell, and complexed by thiol ligands, while the other part was associated with phosphate in vacuolar Ca polyphosphate granules. Thiol ligands increased with exposure time, confirming their important role in Cd stress. In pcs1, Cd was also present as vacuolar Ca polyphosphate granules, and diffused in the cell as Cd-thiol complexes. In addition, while it should be regarded with caution, a minor proportion of Cd complexed by carboxyl groups, was potentially provided by starch produced around the pyrenoid and in the chloroplast. Results suggested that pcs1 uses thiol compounds such as PC to a lesser extent for Cd sequestration than wt. In cw15, an excretion of Cd, Ca polyphosphate granules has to be considered. Finally, Cd was detected in the pyrenoid of all strains.

Involvement of oxidative stress and calcium signaling in airborne particulate matter - induced damages in human pulmonary artery endothelial cells.

Recent studies have revealed that particulate matter (PM) exert deleterious effects on vascular function. Pulmonary artery endothelial cells (HPAEC), which are involved in the vasomotricity regulation, can be a direct target of inhaled particles. Modifications in calcium homeostasis and oxidative stress are critical events involved in the physiopathology of vascular diseases. The objectives of this study were to assess the effects of PM2.5 on oxidative stress and calcium signaling in HPAEC. Different endpoints were studied, (i) intrinsic and intracellular production of reactive oxygen species (ROS) by the H2DCF-DA probe, (ii) intrinsic, intracellular and mitochondrial production of superoxide anion (O2-) by electronic paramagnetic resonance spectroscopy and MitoSOX probe, (iii) reactive nitrosative species (RNS) production by Griess reaction, and (vi) calcium signaling by the Fluo-4 probe. In acellular conditions, PM2.5 leads to an intrinsic free radical production (ROS, O2-) and a 4h-exposure to PM2.5 (5-15µg/cm2), induced, in HPAEC, an increase of RNS, of global ROS and of cytoplasmic and mitochondrial O2- levels. The basal intracellular calcium ion level [Ca2+]i was also increased after 4h-exposure to PM2.5 and a pre-treatment with superoxide dismutase and catalase significantly reduced this response. This study provides evidence that the alteration of intracellular calcium homeostasis induced by PM2.5 is closely correlated to an increase of oxidative stress.

Hyperoxia and hypergravity are independent risk factors of atelectasis in healthy sitting humans: a pulmonary ultrasound and SPECT/CT study.

Aeroatelectasis has developed in aircrew flying routine peacetime flights on the latest generation high-performance aircraft, when undergoing excessive oxygen supply. To single out the effects of hyperoxia and hypergravity on lung tissue compression, and on ventilation and perfusion, eight subjects were studied before and after 1 h 15 min exposure to +1 to +3.5 Gz in a human centrifuge. They performed the protocol three times, breathing air, 44.5% O2, or 100% O2 and underwent functional and topographical imaging of the whole lung by ultrasound and single-photon emission computed tomography combined with computed tomography (SPECT/CT). Ultrasound lung comets (ULC) and atelectasis both increased after exposure. The number of ULC was <1 pre protocol (i.e., normal lung) and larger post 100% O2 (22 ± 3, mean ± SD) than in all other conditions (P < 0.001). Post 44.5% O2 differed from air (P < 0.05). Seven subjects showed low- to medium-grade atelectasis post 100% O2 There was an effect on grade of gas mixture and hypergravity, with interaction (P < 0.001, respectively); 100% O2, 44.5% O2, and air differed from each other (P < 0.05). SPECT ventilation and perfusion were always normal. Ultrasound concurred with CT in showing normal lung in the upper third and ULC/atelectasis in posterior and inferior areas, not for other localizations. In conclusion, hyperoxia and hypergravity are independent risk factors of reversible atelectasis formation. Ultrasound is a useful screening tool. Together with electrical impedance tomography measurements (reported separately), these findings show that zones with decreased ventilation prone to transient airway closure are present above atelectatic areas.

High-grade lymphoma of the bladder visualized on PET.

F-18 FDG PET is used for the staging of many cancers. One of its limits is the analysis of the pelvis and the urinary tract because of physiological radiotracer excretion. We report a rare case of an 82-year-old woman in whom intravenous administration of diuretics (furosemide) allowed the identification of a primary diffuse large B-cell lymphoma of the bladder wall. This pharmaceutical increases urine flow and, therefore, reduces the concentration of radiotracer in the urinary tract, improving the visualization of pelvic or urinary tumors. Furosemide administration is an easy, safe, and noninvasive method, even in case of renal insufficiency. Newer PET cameras with high-performance crystals allow rapid acquisitions and improve the tolerance of an examination with diuretic injection. The 3-dimensional reconstruction of images in new PET cameras reduces the occurrence of hyperactive bladder artifacts. The present case illustrates the advantages of furosemide in a rare pathologic entity.

[PET scanning in the initial assessment of lung cancer]. / La tomographie par émission de positons au 18Fluoro-deoxy-glucose (18FDG-TEP) et le bilan initial du cancer bronchique.

18FDG-PET scanning enables the imaging of metabolic activity giving an assessment of the local extent of thoracic malignancies as well as an indication of the presence of nodal or metastatic spread. This enables more accurate staging and has revolutionised the management of lung cancer. National and international guidelines describe the role of this technique.

[18-FDG positon emission tomography and distal metastasis from lung cancer]. / Tomographie à émission de positons au [18F]-FDG et métastases distales dans les cancers broncho-pulmonaires.

"Whole body" FDG-PET usually covers the body from the base of the skull to the upper third of the thighs, arms in abduction. Thus, the upper part of the head and the lower limbs are not included in the acquisition field. We report the cases of three patients with non-small-cell lung cancer who developed secondary distal localizations beyond the acquisition field of "whole body" FDG-PET. Lung cancer is known to favor hematogenic dissemination, raising the possibility of early distal metastasis. A pretherapeutic PET scan which includes the extremities can be useful to search for distal extension. These true whole body scans are time consuming and can thus limit machine availability. Furthermore, the diagnostic yield of this type of examination may be low since it can be estimated that about 1% of patients will develop isolated distal metastases (3 out of 293 patients in our series initially treated for non-metastatic non-small-cell lung cancer). In the current context of technical availability, systematic inclusion of the lower limbs in the PET scan acquisition field would not appear warranted for the initial work-up of patients with non-small-cell lung cancer. However, clinicians must be aware that distal metastases (brain, lower limbs) may not be detected.

Response surface analysis of chlortetracycline and tetracycline production with K-carrageenan immobilized Streptomyces aureofaciens.

A full-factorial experimental design at three levels with two independent variables, carrageenan concentration (1.0, 1.5, and 2.0%) and potassium chloride concentration (0.3, 0.7, and 1.1 M) was studied in order to analyze the effect of both factors on the antibiotic production of K-carrageenan-immobilized mycelia of Streptomyces aureofaciens. The response surfaces obtained have indicated that both carrageenan and potassium chloride concentrations have a pronounced effect on the yield of chlortetracycline (CTC) and tetracycline (TC) produced by S. aureofaciens. By exclusively varying the immobilization conditions, the tetracycline production can be enhanced more than eight times (12.3 mg g-1 biomass for immobilized cells vs. 1.5 mg g-1 biomass for free cells) in comparison with free-cell mycelial cultures.

[Single center experience of (18F)-fluorocholine positron emission tomography: analysis of its impact on salvage local therapy in patients with prostate adenocarcinoma]. / Expérience monocentrique de la tomographie par émission de positons à la (18F)-fluorocholine : analyse de son impact sur les indications de traitement local de rattrapage dans la prise en charge des adénocarcinomes prostatiques.

PURPOSE: To assess usefulness of ((18)F)-fluorocholine positron emission tomography (PET) for localizing relapse in patients with biochemical relapse from prostate adenocarcinoma and its impact on indications of salvage local therapy. PATIENTS AND METHODS: An ((18)F)-fluorocholine PET coupled with computed tomography was performed in 28 patients with biochemical progression from prostate adenocarcinoma. At the time of ((18)F)-fluorocholine PET, median prostate specific antigen (PSA) was 3.0 ng/mL (from 0.34 to 93 ng/mL) and 17 patients (60.7%) received hormone therapy. Eighteen patients from this cohort were potentially candidates to salvage radiotherapy. RESULTS: A pathologic uptake was shown in 11 patients (39.3%) and 17 patients (60.7%) had no pathologic uptake. Median PSA was 2.4 ng/mL (0.33 to 36 ng/mL) in case of negative ((18)F)-fluorocholine PET, versus 6.75 ng/mL (1.21 to 93 ng/mL) in case of pathologic uptake (P=0.04). Among the 17 patients candidates to salvage radiotherapy, ((18)F)-fluorocholine PET helped deciding for salvage radiotherapy in five patients, since it showed only centropelvic pathologic uptake (27.7%). In one patient, it showed metastatic and radiotherapy was contraindicated. After prostatectomy, ((18)F)-fluorocholine PET was positive in only one patient candidate to salvage radiotherapy (9.1%), showing anastomotic relapse. CONCLUSION: ((18)F)-fluorocholine was positive in about a third of patients with biochemical progression. Its clinical impact is being prospectively investigated.

[Use of positron emission tomography in sarcoidosis]. / Apport de la tomographie par émission de positons dans la prise en charge de la sarcoïdose.

FDG-PET, now hybrid positron emission tomography/computed tomography (PET-CT), has become an established diagnostic tool in oncology. Fluorodesoxyglucose ((18)F-FDG) is not specific for malignant lesions, as uptake of the tracer depends on its accumulation in cells with an increased glucose metabolism as it is also the case in infectious and inflammatory lesions, like sarcoidosis. Thus, FDG-PET has been proposed for internal medicine indications, one of whom is sarcoidosis. The main characteristics of FDG-PET are its better sensitivity compared to (67)Ga scintigraphy and its ability to be used as an earlier marker of therapeutic response as compared with anatomy-based and conventional scintigraphic imaging. However, FDG-PET should be used in atypical or advanced stage of the disease. Future prospective studies should be awaited before integrating FDG-PET in clinical routine for treatment outcome and disease activity assessment in sarcoidosis. New radiopharmaceutical probes are under development and will improve the performance of PET.

[Advances in adults' gliomas biology, imaging and treatment]. / Actualités dans la biologie, l'imagerie et le traitement des gliomes de l'adulte.

A better understanding of gliomas biology is now leading to a combined histo-molecular classification of these tumors. In anaplastic gliomas ongoing studies depend on 1p/19q codeletion status and in glioblastomas on MGMT methylation status. Advanced brain tumor imaging elicits a better identification of gliomas evolutive potential of. In low-grade gliomas, the importance of maximal resection and the role of chemotherapy are being increasingly recognized. In anaplastic gliomas, phase III studies have clarified the respective roles of chemotherapy and radiotherapy. In glioblastomas concomitant chemoradiotherapy is the standard. Most targeted therapies, namely anti-EGFR therapies have failed to demonstrate efficacy but anti-angiogenics are promising. The aim of this review is to discuss the main advances in adults' gliomas biology, imaging and treatment.