Luca Nuvoli

Background: Colorectal cancer (CRC) is the third most diagnosed malignancy and the second leading cause of cancer-related mortality worldwide. Recent therapeutic advancements have significantly improved clinical management, underscoring the importance of routine molecular profiling to guide personalised treatment strategies. This study aims to evaluate the prognostic impact of main molecular alterations—including allele frequency (AF) of RAS mutations—on survival outcomes in a real-world hospital-based cohort of patients with metastatic CRC. Methods: A total of 208 consecutive patients with a histologically confirmed diagnosis of CRC and complete clinical, molecular, and survival data were retrospectively analysed. Somatic mutations in KRAS, NRAS, BRAF, and the occurrence of microsatellite instability (MSI) were assessed using pyrosequencing and real-time PCR assays, respectively, on formalin-fixed, paraffin-embedded tumour samples. Associations between mutational status, clinicopathological parameters, and overall survival (OS) were evaluated. Results: Overall, 138 patients (66.3%) harboured at least one somatic mutation: 115 (55.3%) in KRAS, 8 (3.8%) in NRAS, and 15 (7.2%) in BRAF. MSI was detected in 17/208 (8.2%) patients. A statistically significant improvement in OS was observed in patients lacking mutations in any of the three genes—referred to as wild-type (WT) patients—with BRAF mutated cases showing the worst survival (p = 0.041). Increasing age at the time of first-line therapy for advanced disease stage was associated with a statistically significant increase in the hazard of death (p = 0.031). Conclusions: In the advanced disease stage, RAS/BRAF wild-type colorectal cancers were significantly associated with a survival advantage.

Immunotherapy (IMMUNO) and targeted therapy (TT) have revolutionised melanoma treatment. However, adverse events (AEs) remain frequent and may affect treatment adherence. Female sex has been linked to a higher risk of AEs in cytotoxic therapies. This systematic review and meta-analysis investigate the effect of Sex and Gender (S/G) on AEs during IMMUNO and/or TT in melanoma. Independent studies published up to April 2024 reporting toxicity by S/G in melanoma patients were included. Summary Odds Ratios (sOR) and 95% Confidence Intervals (CI) were calculated using random-effects models. Sixty-nine studies were included. Women had a significantly higher risk of thyroid-related AEs compared to men (sOR = 2.00, 95% CI: 1.41–2.82, I² = 32%). No significant S/G differences were found for Grade III-IV, dermatological, gastrointestinal, hypophysis, kidney, liver, or ocular toxicities. This meta-analysis highlights a S/G based difference in the occurrence of thyroid-related AEs, particularly during first-line treatment. The observed association of dermatological AEs with TT in women, while intriguing, is based on limited evidence and should be considered hypothesis-generating. Overall, these findings suggest the need for closer monitoring of women for thyroid-related, dermatological, and severe AEs, with future studies warranted to confirm these signals in larger, adequately powered cohorts.

e21542 Background: Immunotherapy and target therapy have revolutionized melanoma treatment. However, adverse events (AEs) are still frequent and might impact treatment adherence. Female sex was demonstrated to be associated with a higher risk of AEs from cytotoxic therapy related to cancer treatment. This study aims to conduct a systematic review and meta-analysis to investigate Sex and Gender (S/G) effect on adverse events. Methods: We extracted data from independent studies published until April 2024 with information regarding toxicity by S/G. Only studies that involved patients with melanoma as primary disease were included. Summary Odds ratios OR (sOR) estimates were obtained through random-effects models, and 95% Confidence Intervals (CI) were estimated. I ² was used to evaluate the between-study heterogeneity. Publication bias was investigated with Begg and Egger tests. Results: Information regarding toxicity and gender were extracted from seventy articles. A significant increase in AE related to the thyroid was observed in women (sOR = 2.01, 95%CI [1.41-2.85], I² = 29). S/G did not affect Grade III-IV, Dermatological, Gastrointestinal, Hypophyses, Kidney, Liver or Ocular toxicities. The increased risk of AE related to the thyroid was mainly seen in those undergoing first-line treatments, sOR = , 2.16 [1.36-3.42], and those who underwent mono and combo therapy. Women undergoing TT (target therapy) had an increased risk of dermatological (sOR = 1.94, 95%CI 1.51-2.50, I² = 0%) AE. Conclusions: This study supports and extends the discussion on the impact of S/G on the development of toxicities. Women have an increased risk of AE related to the thyroid, mainly seen during first-line treatment, and showed an increased risk of dermatological AE when treated with TT. Women should be monitored closely for precursor signs of thyroid-related AE, as well as dermatological and generally severe AE, to preserve good treatment adherence.

Disposing of residual cooking oil is a major environmental concern, so its conversion into commercial products is a desirable goal. To design the chemical modification of a domestic waste oil into valuable biochemicals other than biodiesel, we analyzed a series of its samples, collected over a period of three years, using quantitative ¹H-NMR. This analysis, allowing a quick determination of its main chemical characteristics, has rendered the image of a vegetable oil with an almost constant composition over time and with a relative low content of saturated fatty acids. To make this collection protocol more economical, we projected its chemical transformation into esters and epoxidized esters of long chain and branched alcohols, which could find employment as biolubricants and/or bioplasticizers. The one-pot transesterification of the waste cooking oil into esters of commercially available and biodegradable Guerbet alcohols was obtained under environmentally friendly conditions by employing commercial CaO as a catalyst. Additionally, microwave irradiation of this reaction allowed to optimize the energy expenditure by significantly reducing the reaction time as compared with reactions run under conventional heating. To improve their oxidation stabilities, the resulting esters were epoxidized under conditions useful to minimize side-reactions. An investigation of their main rheological properties shows that some of the resulting products display characteristics that make their use as biolubricants or bioplasticizers predictable. The entire process represents a virtuous example of circular economy. Graphical Abstract

The acid-promoted epoxidation of vegetable oils was studied using a variety of acidic ion exchange resins as heterogeneous acid catalysts. Quantitative and selective epoxidation of a series of vegetable oils with different composition of saturated, mono-, di- and tri-unsaturated fatty acids was obtained upon identification of the more efficient catalyst and experimental conditions. Furthermore, optimized reaction conditions were successfully applied to the epoxidation of a waste cooking oil, thus extending our procedure to the valorization of a biowaste, an area of increasing importance within a more sustainable society. The use of quantitative ¹ HNMR besides making accurate evaluation of the amounts of reagents to be employed and of the selectivity, allowed facile and rapid quantification of mono-, di- and tri-epoxides, thus providing an indirect indication on the fatty acid composition of the vegetable oils, even in the presence of very low quantities of linolenic acid.

Cyclopentyl methyl ether and 2-methyltetrahydrofuran, low impact ethereal solvents forming a positive azeotrope with water, were successfully employed as solvents in the synthesis of a variety of acetals carried out under Dean–Stark conditions in the presence of heterogeneous acidic catalysts. Under these conditions, ammonium salts, either as such or supported on SiO₂, performed better or equally well than widely employed homogeneous and heterogeneous acidic catalysts such as p-toluenesulfonic acid, Amberlyst 15^®, or Montmorillonite K10. Several examples highlight the advantage of tuning the relative acidities of ammonium salts by appropriately selecting the counterion. Within one of these examples, our protocol clearly outweighs the classic p-toluenesulfonic acid/toluene protocol in terms of chemoselectivity. Silica-supported catalysts were characterized by SEM, TEM, and FTIR spectroscopies, as well as by N₂ physisorption. Such a characterization reveals an even distribution of ammonium salts on silica, thus confirming the formation of expected catalytic supports.

The effects of ball milling treatment on both the structure and properties of guar gum (GG), tara gum (TG), and methylcellulose (MC) were analyzed prior to assessing their potential interactions with starch components when they are used alone or in blends in a corn starch–rice flour system. X-ray diffraction profiles showed that the ball milling caused a reduction in the crystallin domain and, in turn, a diminished viscosity of the GG aqueous solutions. Despite an increase in its viscosity properties, effects on TG were minimal, while the milled MC exhibited reduced crystallinity, but similar viscosity. When both milled and un-milled hydrocolloids were individually added to the starch–flour system, the pasting properties of the resulting mixtures seemed to be affected by the type of hydrocolloid added rather than the structural changes induced by the treatment. All hydrocolloids increased the peak viscosity of the binary blends (especially pure GG), but only milled and un-milled MC showed values of setback and final viscosity similar to those of the individual starch. Ball milling seemed to be more effective when two combined hydrocolloids (milled GG and MC) were simultaneously used. No significant differences were observed in the viscoelastic properties of the blends, except for un-milled GG/starch, milled TG/starch, and milled MC/milled TG/starch gels.

In this work, semi‐interpenetrating gels of poly(N‐isopropyl acrylamide) and methylcellulose were successfully synthesized by using the Frontal Polymerization (FP) technique. The gels were obtained in the presence of dimethyl sulfoxide and trihexyltetradecylphosphonium persulfate, as polymerization solvent and radical initiator, respectively, hence avoiding the formation of bubbles during polymerization. Then, some of the gels containing dimethyl sulfoxide were thoroughly washed with water, hence obtaining the corresponding hydrogels. The effects of the ratio between poly(N‐isopropyl acrylamide) and methylcellulose, the amount of crosslinker and solvent medium (i.e., dimethyl sulfoxide and water) were thoroughly studied, assessing the influence of temperature and velocity of FP fronts on the glass transition temperature values (dried samples), on the swelling behavior and on the dynamic‐mechanical properties (gels swollen both in water and dimethyl sulfoxide). © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 437–443