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  • 1
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    Online Resource
    DNA FISH Diagnostic Assay on Cytological Samples of Thyroid Follicular Neoplasms
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 9 ( 2020-09-06), p. 2529-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 9 ( 2020-09-06), p. 2529-
    Abstract: Although fine-needle aspiration cytology (FNAC) is helpful in determining whether thyroid nodules are benign or malignant, this distinction remains a cytological challenge in follicular neoplasms. Identification of genomic alterations in cytological specimens with direct and routine techniques would therefore have great clinical value. A series of 153 cases consisting of 72 and 81 histopathologically confirmed classic follicular adenomas (cFAs) and classic follicular thyroid carcinomas (cFTCs), respectively, was studied by means of different molecular techniques in three different cohorts of patients (pts). In the first cohort (training set) of 66 pts, three specific alterations characterized by array comparative genomic hybridization (aCGH) were exclusively found in half of cFTCs. These structural abnormalities corresponded to losses of 1p36.33-35.1 and 22q13.2-13.31, and gain of whole chromosome X. The second independent cohort (validation set) of 60 pts confirmed these data on touch preparations of frozen follicular neoplasms by triple DNA fluorescent in situ hybridization using selected commercially available probes. The third cohort, consisting of 27 archived cytological samples from an equal number of pts that had been obtained for preoperative FNAC and morphologically classified as and histologically verified to be follicular neoplasms, confirmed our previous findings and showed the feasibility of the DNA FISH (DNA fluorescent in situ hybridization) assay. All together, these data suggest that our triple DNA FISH diagnostic assay may detect 50% of cFTCs with a specificity higher than 98% and be useful as a low-cost adjunct to cytomorphology to help further classify follicular neoplasms on already routinely stained cytological specimens.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12092529
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
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  • 2
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    Tolerance and Effectiveness of Targeted Therapies in Aged Patients with Metastatic Melanoma
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 12 ( 2021-06-18), p. 3042-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 12 ( 2021-06-18), p. 3042-
    Abstract: Purpose: Melanoma’s incidence is increasing, and elderly people could be significantly impacted since the majority occurs in people over 65 years of age. Combined BRAF and MEK targeted therapies (TT) are current standard regimen for BRAF mutated metastatic melanoma (MM). Except for subgroups of pivotal trials, little data are available for TT in this population. Materials and Methods: Outcomes were explored in real life patients from MelBase, a French multicentric biobank dedicated to the prospective follow-up of unresectable stage III or IV melanoma. Patients treated by BRAF TT and/or MEK TT combined or not, were included from 2013 to 2017 in 2 groups: group 1 ≤ 65-year-old (yo), group 2 〉 65 yo, analyzed for tolerance and efficacy. Results: 353 patients were included: 231 in group 1, 122 in group 2. Median follow-up was 12 months (M). Median time of treatment was 6.9 M. A total of 80% had at least one Adverse Effect (AE). Most frequent AE (all grades) were mainly skin and subcutaneous, general, and gastrointestinal disorders. A total of 31% of AE were grade 3–4: 28% in group 1 and 39% in group 2 (p = 0.05). No differences were observed in all AE grades proportion, dose modifications, interruptions, and discontinuations. For each group, median overall survival was 20.3 M (CI 95%: 15.5–27.9) and 16.3 M (CI: 14.5–26.9), respectively (p = 0.8). Median progression free survival was 7.8 M (6.4–9.9) and 7.7 M (CI: 5.8–11.3) (p = 0.4). Objective response rate was 59% and 50% (p = 0.6). Conclusion: This study on a large multicentric cohort is the first to assess that TT is well tolerated in elderly BRAF-mutated patients such as in patients younger than 65. Efficacy was similar between groups with outcomes reaching those from pivotal studies. There is thus no argument against using TT in elderly people, although an onco-geriatric opinion is welcome for the most vulnerable.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13123042
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 3
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    Marine Collagen Hydrolysates Downregulate the Synthesis of Pro-Catabolic and Pro-Inflammatory Markers of Osteoarthritis and Favor Collagen Production and Metabolic Activity in Equine Articular Chondrocyte Organoids
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 2 ( 2021-01-08), p. 580-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 2 ( 2021-01-08), p. 580-
    Abstract: Articular cartilage experiences mechanical constraints leading to chondral defects that inevitably evolve into osteoarthritis (OA), because cartilage has poor intrinsic repair capacity. Although OA is an incurable degenerative disease, several dietary supplements may help improve OA outcomes. In this study, we investigated the effects of Dielen® hydrolyzed fish collagens from skin (Promerim®30 and Promerim®60) and cartilage (Promerim®40) to analyze the phenotype and metabolism of equine articular chondrocytes (eACs) cultured as organoids. Here, our findings demonstrated the absence of cytotoxicity and the beneficial effect of Promerim® hydrolysates on eAC metabolic activity under physioxia; further, Promerim®30 also delayed eAC senescence. To assess the effect of Promerim® in a cartilage-like tissue, eACs were cultured as organoids under hypoxia with or without BMP-2 and/or IL-1β. In some instances, alone or in the presence of IL-1β, Promerim®30 and Promerim®40 increased protein synthesis of collagen types I and II, while decreasing transcript levels of proteases involved in OA pathogenesis, namely Htra1, and the metalloproteinases Mmp1-3, Adamts5, and Cox2. Both Promerim® hydrolysates also decreased Htra1 protein amounts, particularly in inflammatory conditions. The effect of Promerim® was enhanced under inflammatory conditions, possibly due to a decrease in the synthesis of inflammation-associated molecules. Finally, Promerim® favored in vitro repair in a scratch wound assay through an increase in cell proliferation or migration. Altogether, these data show that Promerim®30 and 40 hold promise as dietary supplements to relieve OA symptoms in patients and to delay OA progression.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22020580
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
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  • 4
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    PET Imaging for Initial Staging and Therapy Assessment in Multiple Myeloma Patients
    MDPI AG ; 2017
    In:  International Journal of Molecular Sciences Vol. 18, No. 2 ( 2017-02-18), p. 445-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 18, No. 2 ( 2017-02-18), p. 445-
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms18020445
    Language: English
    Publisher: MDPI AG
    Publication Date: 2017
    detail.hit.zdb_id: 2019364-6
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  • 5
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    Bone Marrow MSC Secretome Increases Equine Articular Chondrocyte Collagen Accumulation and Their Migratory Capacities
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 10 ( 2022-05-21), p. 5795-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 10 ( 2022-05-21), p. 5795-
    Abstract: Equine osteoarthritis (OA) leads to cartilage degradation with impaired animal well-being, premature cessation of sport activity, and financial losses. Mesenchymal stem cell (MSC)-based therapies are promising for cartilage repair, but face limitations inherent to the cell itself. Soluble mediators and extracellular vesicles (EVs) secreted by MSCs are the alternatives to overcome those limitations while preserving MSC restorative properties. The effect of equine bone marrow MSC secretome on equine articular chondrocytes (eACs) was analyzed with indirect co-culture and/or MSC-conditioned media (CM). The expression of healthy cartilage/OA and proliferation markers was evaluated in eACs (monolayers or organoids). In vitro repair experiments with MSC-CM were made to evaluate the proliferation and migration of eACs. The presence of nanosized EVs in MSC-CM was appraised with nanoparticle tracking assay and transmission electron microscopy. Our results demonstrated that the MSC secretome influences eAC phenotype by increasing cartilage functionality markers and cell migration in a greater way than MSCs, which could delay OA final outcomes. This study makes acellular therapy an appealing strategy to improve equine OA treatments. However, the MSC secretome contains a wide variety of soluble mediators and small EVs, such as exosomes, and further investigation must be performed to understand the mechanisms occurring behind these promising effects.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23105795
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
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  • 6
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    Marine Collagen Hydrolysates Promote Collagen Synthesis, Viability and Proliferation While Downregulating the Synthesis of Pro-Catabolic Markers in Human Articular Chondrocytes
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 7 ( 2021-04-01), p. 3693-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 7 ( 2021-04-01), p. 3693-
    Abstract: Cartilage is a non-innervated and non-vascularized tissue. It is composed of one main cell type, the chondrocyte, which governs homeostasis within the cartilage tissue, but has low metabolic activity. Articular cartilage undergoes substantial stresses that lead to chondral defects, and inevitably osteoarthritis (OA) due to the low intrinsic repair capacity of cartilage. OA remains an incurable degenerative disease. In this context, several dietary supplements have shown promising results, notably in the relief of OA symptoms. In this study, we investigated the effects of collagen hydrolysates derived from fish skin (Promerim®30 and Promerim®60) and fish cartilage (Promerim®40) on the phenotype and metabolism of human articular chondrocytes (HACs). First, we demonstrated the safety of Promerim® hydrolysates on HACs cultured in monolayers. Then we showed that, Promerim® hydrolysates can increase the HAC viability and proliferation, while decreasing HAC SA-β-galactosidase activity. To evaluate the effect of Promerim® on a more relevant model of culture, HAC were cultured as organoids in the presence of Promerim® hydrolysates with or without IL-1β to mimic an OA environment. In such conditions, Promerim® hydrolysates led to a decrease in the transcript levels of some proteases that play a major role in the development of OA, such as Htra1 and metalloproteinase-1. Promerim® hydrolysates downregulated HtrA1 protein expression. In contrast, the treatment of cartilage organoids with Promerim® hydrolysates increased the neosynthesis of type I collagen (Promerim®30, 40 and 60) and type II collagen isoforms (Promerim®30 and 40), the latter being the major characteristic component of the cartilage extracellular matrix. Altogether, our results demonstrate that the use of Promerim® hydrolysates hold promise as complementary dietary supplements in combination with the current classical treatments or as a preventive therapy to delay the occurrence of OA in humans.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22073693
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
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  • 7
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    Glucose Metabolism Quantified by SUVmax on Baseline FDG-PET/CT Predicts Survival in Newly Diagnosed Multiple Myeloma Patients: Combined Harmonized Analysis of Two Prospective Phase III Trials
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 9 ( 2020-09-06), p. 2532-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 9 ( 2020-09-06), p. 2532-
    Abstract: Background: Multiple myeloma is a hematological neoplasm characterized by a clonal proliferation of malignant plasma cells in the bone marrow, and is associated with high morbidity and mortality and variable survival. Positron emission tomography combined with computed tomography using 18F-deoxyfluoroglucose (FDG-PET/CT) is a promising technique for initial staging of symptomatic multiple myeloma patients. The objective of this study was to assess the prognostic value of this technique at baseline in symptomatic multiple myeloma patients included in two large European prospective studies (French and Italian). Methods: We retrospectively performed a combined harmonized analysis of 227 newly diagnosed transplant eligible multiple myeloma patients from two separate phase III trials. All images were centrally reviewed and analyzed using visual criteria and maximal standardized uptake value. An ad-hoc approach (called modified Combat) was applied to harmonize the data and then remove the “country effect” in order to strengthen the reliability of the final conclusions. Results: Using a multivariate analysis including treatment arm, R-ISS score, presence of extra-medullary disease and bone SUVmax, only bone SUVmax (p = 0.016) was an independent prognosis factor with an OS threshold of 7.1. For PFS, treatment arm and presence of extra-medullary disease were both independent prognosis biomarkers (p = 0.022 and 0.006 respectively). Conclusions: Our results show that bone SUVmax is a simple and reliable biomarker to analyze FDG-PET/CT at baseline that strongly correlates with a poorer prognosis for MM patients.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12092532
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
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  • 8
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    A Comparative Study of the Electro-Assisted Grafting of Mono- and Bi-Phosphonic Acids on Nitinol
    MDPI AG ; 2019
    In:  Surfaces Vol. 2, No. 4 ( 2019-09-29), p. 520-530
    Details
    In: Surfaces, MDPI AG, Vol. 2, No. 4 ( 2019-09-29), p. 520-530
    Abstract: Over the last few years, Nitinol (NiTi) has become one of the most attractive alloy materials for industrial applications. However, its implementation is still problematic due to its surface nickel content, making it sensitive to pitting corrosion. In applications, it is often necessary to modify NiTi surfaces by using organic coatings, which provides new physico-chemical properties as well as functionalities and often contributes to a reinforcement of the alloy corrosion resistance. In this work, we assess the differences between the molecular layers made out of methylphosphonic acid (C1P) and the bi-phosphonic acid derivatives: (methylimino)dimethylene-bisphophonic acid (MIP2) and 1-hydroxyethylidene-1,1-diphosphonic acid (HEP2) using conventional (CG) and electro-assisted (EG) graftings. The surface modifications with the bi-phosphonic derivatives (MIP2) and (HEP2) carried out with the EG process lead to denser layers and a reinforced NiTi corrosion resistance.
    Type of Medium: Online Resource
    ISSN: 2571-9637
    URL: Article
    DOI: 10.3390/surfaces2040038
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 3008275-4
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  • 9
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    Mobile Laser Scanning for Estimating Tree Structural Attributes in a Temperate Hardwood Forest
    MDPI AG ; 2022
    In:  Remote Sensing Vol. 14, No. 18 ( 2022-09-10), p. 4522-
    Details
    In: Remote Sensing, MDPI AG, Vol. 14, No. 18 ( 2022-09-10), p. 4522-
    Abstract: The emergence of mobile laser scanning (MLS) systems that use simultaneous localization and mapping (SLAM) technology to map their environment opens up new opportunities for characterizing forest structure. The speed and accuracy of data acquisition makes them particularly adapted to operational inventories. MLS also shows great potential for estimating inventory attributes that are difficult to measure in the field, such as wood volume or crown dimensions. Hardwood species represent a significant challenge for wood volume estimation compared to softwoods because a substantial portion of the volume is included in the crown, making them more prone to allometric bias and more complex to model. This study assessed the potential of MLS data to estimate tree structural attributes in a temperate hardwood stand: height, crown dimensions, diameter at breast height (DBH), and merchantable wood volume. Merchantable wood volume estimates were evaluated to the third branching order using the quantitative structural modeling (QSM) approach. Destructive field measurements and terrestrial laser scanning (TLS) data of 26 hardwood trees were used as reference to quantify errors on wood volume and inventory attribute estimations from MLS data. Results reveal that SLAM-based MLS systems provided accurate estimates of tree height (RMSE = 0.42 m (1.78%), R2 = 0.93), crown projected area (RMSE = 3.23 m2 (5.75%), R2 = 0.99), crown volume (RMSE = 71.4 m3 (23.38%), R2 = 0.99), DBH (RMSE = 1.21 cm (3.07%), R2 = 0.99), and merchantable wood volume (RMSE = 0.39 m3 (18.57%), R2 = 0.95), when compared to TLS. They also estimated operational merchantable volume with good accuracy (RMSE = 0.42 m3 (21.82%), R2 = 0.94) compared to destructive measurements. Finally, the merchantable stem volume derived from MLS data was estimated with high accuracy compared to TLS (RMSE = 0.11 m3 (8.32%), R2 = 0.96) and regional stem taper models (RMSE = 0.16 m3 (14.7%), R2 = 0.93). We expect our results would provide a better understanding of the potential of SLAM-based MLS systems to support in-situ forest inventory.
    Type of Medium: Online Resource
    ISSN: 2072-4292
    URL: Article
    DOI: 10.3390/rs14184522
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2513863-7
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  • 10
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    Functional Imaging for Therapeutic Assessment and Minimal Residual Disease Detection in Multiple Myeloma
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 15 ( 2020-07-29), p. 5406-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 15 ( 2020-07-29), p. 5406-
    Abstract: Serum markers and bone marrow examination are commonly used for monitoring therapy response in multiple myeloma (MM), but this fails to identify minimal residual disease (MRD), which frequently persists after therapy even in complete response patients, and extra-medullary disease escape. Positron emission tomography with computed tomography using 18F-deoxyglucose (FDG-PET/CT) is the reference imaging technique for therapeutic assessment and MRD detection in MM. To date, all large prospective cohort studies of transplant-eligible newly diagnosed MM patients have shown a strong and independent pejorative prognostic impact of not obtaining complete metabolic response by FDG-PET/CT after therapy, especially before maintenance. The FDG-PET/CT and MRD (evaluated by flow cytometry or next-generation sequencing at 10−5 and 10−6 levels, respectively) results are complementary for MRD detection outside and inside the bone marrow. For patients with at least a complete response, to reach double negativity (FDG-PET/CT and MRD) is a predictive surrogate for patient outcome. Homogenization of FDG-PET/CT interpretation after therapy, especially clarification of complete metabolic response definition, is currently underway. FDG-PET/CT does not allow MRD to be evaluated when it is negative at initial workup of symptomatic MM. New PET tracers such as CXCR4 ligands have shown high diagnostic value and could replace FDG in this setting. New sensitive functional magnetic resonance imaging (MRI) techniques such as diffusion-weighted MRI appear to be complementary to FDG-PET/CT for imaging MRD detection. The goal of this review is to examine the feasibility of functional imaging, especially FDG-PET/CT, for therapeutic assessment and MRD detection in MM.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21155406
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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