Impact of cemiplimab treatment duration on clinical outcomes in advanced cutaneous squamous cell carcinoma.

Treatment duration with checkpoint inhibitors must be optimized to prevent unjustified toxicity, but evidence for the management of cutaneous squamous cell carcinoma is lacking. A retrospective study was performed to evaluate the survival of patients with cutaneous squamous cell carcinoma (CSCC) who discontinued cemiplimab due to different causes and without progression. Among 95 patients with CSCC who received cemiplimab, 22 (23%) patients discontinued immunotherapy due to causes other than progression, such as comorbidities, toxicity, complete response or lack of compliance (group that discontinued before censoring [DBC]), then 73 patients had standard treatment scheduled (STS).

'Sorrento' and 'Tulare' Walnut Cultivars: Morphological Traits and Phytochemical Enhancement of Their Shell Waste.

Walnut processing generates considerable quantities of by-products that could be reprocessed into value-added products that have food and non-food applications. In this context, the aim of this study is to characterize the 'Sorrento' and 'Tulare' walnut cultivars using the UPOV guidelines and analyze the chemical composition and antioxidant activity of their shells. Insight into the chemical composition of the different granulometric fractions of walnut shell, obtained by sieving, was obtained following ultrasound-assisted extraction by Ultra-High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry (UHPLC-HRMS).

: Assessment of the Antiviral Activity of Lipophilic Extracts from Its Organs.

In a framework aimed at the recovery and enhancement of medicinal plants endemic to the territory of the Cilento and Vallo di Diano National Park, N.G. Passal.

(Lamiaceae): Getting Insights into Bioactive Polyphenols of a Rare Italian Endemic Vascular Plant.

N.G. Passal.

Encapsulating (Vaill.) L. Florets: UHPLC-HRMS Insights into Bioactive Compounds Preservation and Oral Bioaccessibility.

Wild edible plants, once consumed in times of famine or for health purposes, today represent an interesting dietary supplement, aimed at enriching local dishes and/or formulating healthy nutraceutical products. In fact, the broad content of different, and diversely bioactive, specialized metabolites therein suggests new scenarios of use which, in order to be as functional as possible, must maximize the bioactivity of these compounds while preserving their chemistry. In this context, based on a recent investigation on the metabolic profile of the organs of that highlighted that florets are abundant in flavonol glycosides and triterpene saponins, the freeze-drying encapsulation of their alcoholic extract (FE) into maltodextrin (MD) was investigated.

A Joint Approach of Morphological and UHPLC-HRMS Analyses to Throw Light on the Autochthonous 'Verdole' Chestnut for Nutraceutical Innovation of Its Waste.

Nowadays, chestnut by-products are gaining a lot of interest as a low-cost raw material, exploitable for developing added-value products. This is in line with suitable chestnut by-products' management, aimed at reducing the environmental impact, thus improving the chestnut industry's competitiveness and economic sustainability. In this context, with the aim of valorizing local cultivars of European chestnuts ( Mill.

LC-HR/MS Analysis of Lipophilic Extracts from (Vaill.) L. Organs: An Unexplored Source in Cosmeceuticals.

As part of a project aimed at promoting the use of (Vaill.) L. (field marigold, Asteraceae) phytocomplexes in cosmeceutical formulations, the chemical composition in apolar specialized metabolites is herein elucidated.

Nivolumab serum concentration in metastatic melanoma patients could be related to outcome and enhanced immune activity: a gene profiling retrospective analysis.

Background: Nivolumab is an anti-PD-1 antibody approved for treating metastatic melanoma (MM), for which still limited evidence is available on the correlation between drug exposure and patient outcomes.

Methods: In this observational retrospective study, we assessed whether nivolumab concentration is associated with treatment response in 88 patients with MM and if the patient's genetic profile plays a role in this association.

Results: We observed a statistically significant correlation between nivolumab serum concentration and clinical outcomes, measured as overall and progression-free survival.

(Vaill.) L.: A Systematic Plant Analysis of the Polar Extracts from Its Organs by UHPLC-HRMS.

(Vaill.) L. (field marigold, Asteraceae) is an alimurgic plant, whose flowers and leaves are a common part of local food dishes.

Phytochemical Characterization of L. Cultivars of Cilento National Park (South Italy) through NMR-Based Metabolomics.

germplasm is constituted by a huge number of cultivars, each one characterized by specific features. In this context, endemic cultivars evolved for a very long period in a precise local area, developing very specific traits. These characteristics include the production and accumulation of phytochemicals, many of which are also responsible for the nutraceutical value of the drupes and of the oils therefrom.

Chemical Fractionation Joint to In-Mixture NMR Analysis for Avoiding the Hepatotoxicity of L. subsp. .

Dietary supplements based on L. subsp. aerial parts were banned, due to the hepatotoxicity of furan-containing -clerodane constituents.

A monocentric phase I study of vemurafenib plus cobimetinib plus PEG-interferon (VEMUPLINT) in advanced melanoma patients harboring the V600BRAF mutation.

Background: Studies carried out in vitro and in a mouse model have shown that BRAF inhibitors enhance the effects of IFN-α on BRAFV600E melanoma cells through the inhibition of ERK. Therefore, the combination of vemurafenib and IFN-α in patients with BRAFV600E melanoma may provide therapeutic benefits; MEK inhibition may prevent the reactivation of the MAPK pathway induced by BRAF inhibitor resistance.

Patients And Methods: In a phase I study, adult patients with advanced BRAFV600-mutated melanoma were treated with vemurafenib + PEG-IFN-α-2b or vemurafenib + cobimetinib + PEG-IFN-α-2b, to assess the safety of the combination and the upregulation of IFN-α/β receptor-1 (IFNAR1).

Melanoma immunotherapy: strategies to overcome pharmacological resistance.

: Although checkpoint inhibitors have provided a breakthrough in how melanoma is treated, about half of patients still do not respond due to primary or acquired resistance. New strategies are, therefore, required to increase the number of patients benefiting from immunotherapy. This systematic review investigates novel combinations that may overcome immune resistance in patients with melanoma.

Frequency of circulating CD8+CD73+T cells is associated with survival in nivolumab-treated melanoma patients.

Background: PD-1 blocking agents, such as nivolumab, have demonstrated clear anti-tumor effects and clinical benefits in a subset of patients with advanced malignancies. Nonetheless, more efforts are needed to identify reliable biomarkers for outcome, to correctly select patients who will benefit from anti-PD-1 treatment. The aim of this study was to investigate the role of peripheral CD8+T cells expressing CD73, involved in the generation of the immune suppressive molecule adenosine, in predicting outcome after nivolumab treatment in advanced melanoma patients.

NMR-based metabolomics and bioassays to study phytotoxic extracts and putative phytotoxins from Mediterranean plant species.

Introduction: Mediterranean plants are characterised by a high content of bioactive secondary metabolites that play important roles in plant-plant interactions as plant growth regulators and could be useful for the development of new eco-friendly herbicides.

Objective: An NMR-based metabolomics approach was reported to seek selective phytotoxic plant extracts and putative plant-derived active molecules.

Methods: Plant extracts derived from five Mediterranean donor species (Pistacia lentiscus, Bellis sylvestris, Phleum subulatum, Petrohrhagia saxifraga and Melilotus neapolitana) were used to treat the hydroponic cultures of three receiving plants (Triticum durum, Triticum ovatum and Avena fatua).

Fire Severity Influences Ecophysiological Responses of Ait.

The effect of fire severity on growth and ecophysiological responses was evaluated in four burned sites of Vesuvio National Park, Southern Italy. After the wildfire of 2017, when over 1300 hectares of vegetation, mainly woods, were destroyed, four sites were selected according to the different degree of fire severity and a multidisciplinary approach based on tree rings, stable isotopes and percentage of crown scorched or consumed was applied. All the sampled trees in the burned sites showed a decrease in tree growth in 2017, in particular in the latewood at high-severity site.

Spectroscopic Characterization and Cytotoxicity Assessment towards Human Colon Cancer Cell Lines of Acylated Cycloartane Glycosides from L.

In several European countries, especially in Sweden, the seeds of the species L. were widely used as coffee substitutes during the 19th century. Nonetheless, data regarding the phytochemistry and the pharmacological properties of this species are currently extremely limited.

Metabolomic approach for a rapid identification of natural products with cytotoxic activity against human colorectal cancer cells.

The discovery of bioactive compounds from natural sources entails an extremely lengthy process due to the timescale and complexity of traditional methodologies. In our study, we used a rapid NMR based metabolomic approach as tool to identify secondary metabolites with anti-proliferative activity against a panel of human colorectal cancer cell lines with different mutation profiles. For this purpose, fourteen Fabaceae species of Mediterranean vegetation were investigated using a double screening method: H NMR profiling enabled the identification of the main compounds present in the mixtures, whilst parallel biological assays allowed the selection of two plant extracts based on their strong anti-proliferative properties.

Correlation between previous treatment with BRAF inhibitors and clinical response to pembrolizumab in patients with advanced melanoma.

The optimal sequencing of targeted treatment and immunotherapy in the treatment of advanced melanoma is a key question and prospective studies to address this are ongoing. Previous observations suggest that treating first with targeted therapy may select for more aggressive disease, meaning that patients may not gain full benefit from subsequent immunotherapy. In a single-center retrospective analysis, we investigated whether response to pembrolizumab was affected by previous BRAF inhibitor therapy.

Highlighting the effects of coumarin on adult plants of Arabidopsis thaliana (L.) Heynh. by an integrated -omic approach.

In this study, the effects of the allelochemical coumarin through a metabolomic, proteomic and morpho-physiological approach in Arabidopsis adult plants (25days old) were investigated. Metabolomic analysis evidenced an increment of amino acids and a high accumulation of soluble sugars, after 6days of coumarin treatment. This effect was accompanied by a strong decrease on plant fresh and dry weights, as well as on total protein content.

Effects of prescribed burning on ecophysiological, anatomical and stem hydraulic properties in Pinus pinea L.

Prescribed burning (PB) is a widespread management technique for wildfire hazard abatement. Understanding PB effects on tree ecophysiology is key to defining burn prescriptions aimed at reducing fire hazard in Mediterranean pine plantations, such as Pinus pinea L. stands.

Chemical Composition and Seasonality of Aromatic Mediterranean Plant Species by NMR-Based Metabolomics.

An NMR-based metabolomic approach has been applied to analyse seven aromatic Mediterranean plant species used in traditional cuisine. Based on the ethnobotanical use of these plants, the approach has been employed in order to study the metabolic changes during different seasons. Primary and secondary metabolites have been detected and quantified.

Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy.

Cancer radiotherapy (RT) may induce what is referred to as the "abscopal effect," a regression of non-irradiated metastatic lesions distant from the primary tumor site directly subject to irradiation. This clinical response is rare, but has been surmised to be an immune-mediated phenomenon, suggesting that immunotherapy and RT could potentially synergize. Here, we report the outcome of patients with advanced melanoma treated with the immune checkpoint blockade monoclonal antibody antagonist, ipilimumab followed by RT.

Chemical interactions between plants in Mediterranean vegetation: the influence of selected plant extracts on Aegilops geniculata metabolome.

Allelopathy is the chemical mediated communication among plants. While on one hand there is growing interest in the field, on the other hand it is still debated as doubts exist at different levels. A number of compounds have been reported for their ability to influence plant growth, but the existence of this phenomenon in the field has rarely been demonstrated.