102,294 research outputs found
Neurological complications of chimeric antigen receptor T cells and immune-checkpoint inhibitors: ongoing challenges in daily practice
No full textPURPOSE OF REVIEW: The aim of this review is to summarize the most recent advances in the management of neurological toxicities associated with immune-checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR)-T cells. RECENT FINDINGS: The advent of cancer immunotherapies has dramatically improved the prognosis of several refractory and advanced neoplasms. Owing to their mechanism of action, cancer immunotherapies have been associated with a variety of immune-related adverse events (irAE). Neurological irAE are uncommon compared with other irAE, but they are associated with significant morbidity and mortality. Despite the efforts to draft common protocols and guidelines, the management of neurological irAE remains challenging. Our ability to predict the development of neurotoxicity is still limited, hampering to elaborate prevention strategies. Treatment heavily relies on the administration of high-dose corticosteroids that, however, have the potential to impair oncological efficacy. The experimentation of novel strategies to avoid resorting to corticosteroids is hindered by the lack of an adequate understanding of the pathogenetic mechanisms driving the development of irAE. SUMMARY: In this review, we will discuss the most recent advances on the diagnosis and management of neurological irAE associated with ICIs and CAR-T cells, focusing on the issues that remain most challenging in clinical practice
Current therapeutic approaches to diffuse grade II and III gliomas
No full textThe 2016 WHO classification of Tumors of the Central Nervous System brought major conceptual and practical changes in the classification of diffuse gliomas, by combining molecular features and histology into ‘integrated’ diagnoses. In diffuse gliomas, molecular profiling has thus become essential for nosological purposes, as well as to plan adequate treatment strategies and identify patients susceptible of target therapy. WHO grade II (low grade) and grade III (anaplastic) diffuse gliomas form a heterogeneous group of neoplasms, also known as ‘lower-grade gliomas’, characterized by a wide range of malignant potential. Molecular profile accounts for this biological diversity, and provides an accurate prognostic stratification of tumors in this group. Treatment strategies in lower-grade gliomas are ultimately based on molecular profile and WHO grade, as well as on patient characteristics such as age and Karnofsky performance status. The purpose of this review is to summarize recent advances in the classification of grade II and III gliomas, synthesize current treatment schemes according to molecular profile and describe ongoing research and future perspectives for the use of target therapies
Characteristics of flame-nucleated carbonaceous nanoparticles
No full textFlame-formed just-nucleated carbon nanoparticles, with sizes of about 2-10 nanometers, have been the object of increasing interest over the last decades not only because of environmental concerns but also as new procedure for synthesis of engineered nanoparticles. In this work, we present an experimental study on synthesis and characterization of carbon nanoparticles generated in a laminar premixed ethylene/air flame. The production of carbon nanoparticles of different sizes and properties is achieved by changing the particle residence time in the flame, i.e., collecting the carbon nanoparticles at different heights above the burner. Particle size distributions, Raman, UV-visible and electron paramagnetic resonance (EPR) spectroscopies have been used to characterize the sampled particles. The size of the particles increases as the residence time in the flame increases, the particle size distributions changing from a unimodal to bimodal. Chemical and structural modifications are retrieved by Raman and EPR analysis. Raman spectra show the G and D bands, typical of disordered carbonaceous materials. Their relative intensity and band position changes during the growing process and are used as index of structural changes. EPR spectroscopy, a powerful tool to probe electronic properties of carbon-based materials, reveals the presence and superposition of multiple paramagnetic species. Persistent carbon-centered aromatic radicals are detected for all the sampled particles and an abrupt change in the EPR signal is observed as the particle distribution changes from monomodal to bimodal. EPR indicate a three-dimensional structural organization when larger particles are formed. Optical proprieties are retrieved by UV-visible spectroscopy which, combined to Raman and EPR spectroscopy, seems to be powerful diagnostics to monitor particle clustering and to control the process of engineered carbonaceous nanoparticle production
Mitotane and Carney Complex: ten years follow-up of a low-dose mitotane regimen inducing a sustained correction of hypercortisolism.
No full textOBJECTIVE: Primary pigmented nodular adrenocortical disease (PPNAD), an uncommon cause of Cushing’s syndrome, is frequently associated with a wider clinical spectrum, the Carney complex (CC), a multiple endocrine neoplasia syndrome. DESIGN: We evaluated a low-dose mitotane regimen for treating severe hypercortisolism in a 27-year-old woman with CC. She presented with severe hypercortisolism and a history of surgeries for breast ductal adenoma, atrial cardiac myxomas with cerebral and peripheral arterial embolism, and near-total thyroidectomy because of an oxyphilic adenoma. The patient refused further surgery for adrenalectomy. RESULTS: During the first 7 months of mitotane (Lysodren, HRA Pharma, Paris, France), the daily oral dose was progressively increased from 0.5 to 4 g/day and then stopped because of the appearance of sustained signs of hypoadrenalism, that required a replacement therapy with 5 mg of prednisone o.d. A 10-month mitotane off-therapy follow-up was performed and when an increase in urine free cortisol (UFC) was noted, the mitotane regimen was restarted at lower doses (0.750-1 g/day). Serum morning cortisol levels and UFC were then maintained within the normal range, with plasma mitotane ranging between 2 and 4 mg/L. A sustained regression of Cushing’s features without inducing hypoadrenalism was achieved, which still persists after 122 months of follow-up. Minimal initial gastric discomfort was the only side effect of which the patient complained and only during the first higher dose mitotane course. CONCLUSIONS: Long-term administration of a low maintenance dose of mitotane may be suggested as treatment for hypercortisolism in CC patients who refuse or are at high risk for surgical adrenalectom
Single and combined use of Cannabis sativa L. and carbon-rich materials for the removal of pesticides and endocrine-disrupting chemicals from water and soil
No full textHemp (Cannabis sativa L.) seedlings were used to remove from water the fungicide metalaxyl-M and the endocrine disruptor (EDC) bisphenol A (BPA) at concentrations ranging from 2 to 100 μg mL-1. In 7 days of exposure, despite the phytotoxicity of each compound that reduced elongation and biomass, the seedlings were able to remove between 67 and 94% of metalaxyl-M and between 86 and 95% of BPA. The amounts of metalaxyl-M and BPA extracted from plant dry biomass were in the range of 106-3861 μg g-1 and 16-101 μg g-1, respectively, and resulted positively correlated to both the dose of compound added (P ≤ 0.01) and the amount removed by the plants (P ≤ 0.01). Plant uptake and transformation were the main mechanisms involved in the removal of the compounds. In another set of experiments, hemp was used to remove a mixture of two pesticides, metalaxyl-M and metribuzin, and three EDCs, BPA, 17β-estradiol (E2), and 4-tert-octylphenol (OP), at concentrations of 10, 10, 10, 10, and 1 μg g-1, respectively, from soil column not added and added with 2.5% (w/w) of a green compost (CM) or a wood biochar (BC). In 25 days, plants did not alter considerably the distribution of the compounds along the soil profile and were capable of removing, on average, 12, 11, 10, 9, and 14% of metalaxyl-M, metribuzin, BPA, E2, and OP, respectively. During growth, hemp transformed the compounds and accumulated part of them (except OP) mainly in the shoots. CM and, especially, BC significantly protected the plants from the toxicity of the compounds and enhanced the retention of the latter in soil, contrasting leaching. Thus, the single or synergistic use of hemp and amendments deserves attention being a very low-cost and eco-sustainable strategy to remediate water and soil
Six months mitotane course induced sustained correction of hypercortisolism in a young woman with PPNAD and Carney Complex.
No full textThe clinical use of IDH1 and IDH2 mutations in gliomas
No full textIntroduction: Mutations in the genes isocitrate dehydrogenase (IDH) 1 and 2 have been reported in a limited number of tumors. In gliomas, IDH mutations are primarily detected in WHO grade II–III tumors and represent a major biomarker with diagnostic, prognostic, and predictive implications. The recent development of IDH inhibitors and vaccines suggests that the IDH mutation is also an appealing target for therapy. Areas covered: This review focuses on the role of IDH mutations in diffuse gliomas. Besides discussing their role in gliomagenesis, we will emphasize the role of IDH mutations in clinical practice as a diagnostic, prognostic and predictive biomarker, and as a potential therapeutic target. Noninvasive detection of the IDH mutation by means of liquid biopsy and MR spectroscopy will also be discussed. Expert commentary: While IDH mutation is a consolidated diagnostic and prognostic biomarker in clinical practice, its role in oncogenesis is far from being elucidated, and there are several pending issues. The routine use of noninvasive techniques for detection and monitoring of the IDH status remains challenging. Although the IDH mutation is a very early alteration in gliomagenesis, it may then be omitted during tumor progression. This observation has important implications when designing targeted clinical trials
Circulating Cell-Free Mitochondrial DNA and Inflammation in Older Adults with Pancreatic Cancer: Results from an Exploratory Study
No full textPancreatic cancer (PaCa) is among the most aggressive malignancies of the digestive system. Inflammation plays a critical role in tumor growth and dissemination, with soluble cytokines serving as messengers that facilitate interactions between immune and cancer cells. The release of cell-free mitochondrial DNA (cf-mtDNA) into the bloodstream has been identified as a potent proinflammatory trigger, acting as a mitochondrial-derived damage-associated molecular pattern (mtDAMP). Whether a relationship exists between circulating cf-mtDNA (ccf-mtDNA) unloading and inflammation in PaCa remains unclear. In this study, we quantified ccf-mtDNA levels in plasma/serum samples from PaCa patients and healthy controls and examined their association with inflammatory markers. Analyses were conducted on 14 participants: 3 controls (mean age: 52.0 ± 16.0 years, 67% women) and 11 PaCa patients (mean age: 69.1 ± 10.0 years, 27% women). Circulating levels of ccf-mtDNA in PaCa patients did not show differences compared to controls (p = 0.06). In contrast, concentrations of interleukin (IL)-8, IL-17, and interferon-gamma were significantly higher in PaCa patients. Stratification of PaCa patients based on the median ccf-mtDNA concentration revealed significantly higher levels of IL-4, IL-9, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein 1-beta in those with ccf-mtDNA levels above the median (p < 0.05). Significant positive associations were also observed between levels of ccf-mtDNA and IL-8, fibroblast growth factor, and MCP-1. These results suggest a potential association between elevated ccf-mtDNA levels and increased concentrations of proinflammatory cytokines, especially in PaCa patients with an unfavorable prognosis. Further research with larger cohorts is required to validate these findings and assess the prognostic value of these biomarkers
Role of radicals in carbon clustering and soot inception: A combined EPR and Raman spectroscopic study
No full textSome aspects of soot formation from gas phase molecules at high temperatures are still unclear. Aromatic π-radicals may be key elements for a change in the model of carbon clustering and particle formation. However, experimental investigations are still needed on the radical nature of molecules and particles in flames and on their roles in the transition from molecules to incipient molecular clusters and their further evolution to mature soot. In this paper, we present electron paramagnetic resonance (EPR) and Raman spectroscopy measurements of particles collected in an ethylene-rich premixed flame at various residence times during nucleation. The experimental results, combined with measurement of the particle size distribution by a differential mobility analyzer, are used to investigate the role of radicals in particle nucleation and rearrangement of aromatic molecules in just-nucleated particles. For all the sampled particles, an EPR signal typical of persistent carbon-centered aromatic radicals is measured. An abrupt change in the EPR signal intensity, which is characteristic of stronger supramolecular interactions, is observed when the size distribution changes from monomodal to bimodal, as confirmed by Raman spectroscopy. Our experimental results indicate strong involvement of π-radicals during particle nucleation and growth. The paramagnetic/radical nature of the sampled particles is discussed on the basis of recent studies on the role of resonantly stabilized radicals in soot nucleation. The presence of localized π-electrons on the edge of aromatic soot constituents and their role in carbon clustering are also discussed
Bibliographie Hilarion G. Petzold 1958 – 2009 mit Anhang als Einführung
No full textDieses Archiv enthält die Gesamtbibliographie der Werke des Autors nebst einiger Texte „Über H. G. Petzold“ im Schlussteil der Bibliographie sowie einen Anhang mit einer Einführung in die Architektur des Werkes in seinem wissenslogischen Aufbau als Ausarbeitung seines „Tree of Science Modells“ (2007).This archive contains the complete bibliography of the author and some texts about H. G. Petzold, moreover an epilogue with an introduction to the architecture of the works in its epistemological structure and composition and as an elaborations of Petzold’s „Tree of Science Modell (2007).https://www.fpi-publikation.de/polyloge/01-2009-petzold-h-g-gesamtbibliographie-h-g-petzold-1958-2009-updating-november2009/peerReviewedpublishedVersio
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