CRISPR/Cas9 screenings unearth protein arginine methyltransferase 7 as a novel essential gene in prostate cancer metastasis.

Due to the limited effectiveness of current treatments, the survival rate of patients with metastatic castration-resistant prostate cancer (mCRPC) is significantly reduced. Consequently, it is imperative to identify novel therapeutic targets for managing these patients. Since the invasive ability of cells is crucial for establishing and maintaining metastasis, the aim of this study was to identify the essential regulators of invasive abilities of mCRPC cells by conducting two independent high-throughput CRISPR/Cas9 screenings. Furthermore, some of the top hits were validated using siRNA technology, with protein arginine methyltransferase 7 (PRMT7) emerging as the most promising candidate. We demonstrated that its inhibition or depletion via genetic or pharmacological approaches significantly reduces invasive, migratory and proliferative abilities of mCRPC cells in vitro. Moreover, we confirmed that PRMT7 ablation reduces cell dissemination in chicken chorioallantoic membrane and mouse xenograft assays. Molecularly, PRMT7 reprograms the expression of several adhesion molecules by methylating various transcription factors, such as FoxK1, resulting in the loss of adhesion from the primary tumor and increased motility of mCRPC cells. Furthermore, PRMT7 higher expression correlates with tumor aggressivity and poor overall survival in prostate cancer patients. Thus, this study demonstrates that PRMT7 is a potential therapeutic target and potential biomarker for mPCa.

Prevalence of immune-related adverse events and anti-tumor efficacy in advanced/metastatic urothelial carcinoma following immune-checkpoint inhibitor treatment

Purpose We evaluated the prevalence of immune-related adverse events and anti-tumor efficacy in advanced/metastatic urothelial carcinoma following immune-checkpoint inhibitors (ICIs) treatment. Methods We conducted a multicenter retrospective study of patients with advanced/metastatic urothelial carcinoma treated with ICIs in four Spanish institutions. irAEs were classified using Common Terminology Criteria for Adverse Event (CTCAE) v.5.0 guidelines. The primary endpoint was overall survival (OS). Other endpoints were overall response rate (ORR) and progression-free survival (PFS). irAEs were evaluated as a time-dependent covariate to avoid immortal time bias. Results A total of 114 patients were treated with ICIs between May 2013 and May 2019, 105 (92%) of whom received ICIs as monotherapy. irAEs of any grade were experienced in 56 (49%) patients and 21 (18%) patients had grade ≥ 3 toxicity. The most frequent irAEs were gastrointestinal and dermatological toxicities, reported in 25 (22%) and 20 (17%) patients, respectively. Patients with grade 1–2 irAEs had significantly longer OS compared to those without grade 1–2 irAEs (median 18.2 vs. 8.7 months, HR = 0.61 [95% CI 0.39–0.95], p = 0.03). No association with efficacy was observed for patients with grade ≥ 3 irAEs. No difference in PFS was observed after adjusting for the immortal time bias. ORR was higher in patients who developed irAEs (48% vs 17%, p < 0.001). Conclusions Our findings suggest that development of irAEs was associated with higher ORR, and patients who developed grade 1–2 irAEs had longer OS. Prospective studies are necessary to confirm our findings (AU)

Cholinergic Polarization of Human Macrophages.

Macrophages serve as vital defenders, protecting the body by exhibiting remarkable cellular adaptability in response to invading pathogens and various stimuli. These cells express nicotinic acetylcholine receptors, with the α7-nAChR being extensively studied due to its involvement in activating the cholinergic anti-inflammatory pathway. Activation of this pathway plays a crucial role in suppressing macrophages' production of proinflammatory cytokines, thus mitigating excessive inflammation and maintaining host homeostasis. Macrophage polarization, which occurs in response to specific pathogens or insults, is a process that has received limited attention concerning the activation of the cholinergic anti-inflammatory pathway and the contributions of the α7-nAChR in this context. This review aims to present evidence highlighting how the cholinergic constituents in macrophages, led by the α7-nAChR, facilitate the polarization of macrophages towards anti-inflammatory phenotypes. Additionally, we explore the influence of viral infections on macrophage inflammatory phenotypes, taking into account cholinergic mechanisms. We also review the current understanding of macrophage polarization in response to these infections. Finally, we provide insights into the relatively unexplored partial duplication of the α7-nAChR, known as dup α7, which is emerging as a significant factor in macrophage polarization and inflammation scenarios.

Fucose modifies short chain fatty acid and H2S formation through alterations of microbial cross-feeding activities.

Algae are a rich but unexplored source of fibers with the potential to contribute to the next generation of prebiotics. The sulfated brown algae polysaccharide, fucoidan, is mainly composed of the deoxy-hexose L-fucose, which can be metabolized to 1,2-propanediol (1,2-PD) or lactate by gut microbes as precursors of propionate and butyrate. It was the aim of this study to investigate the impact of fucoidan on the fermentation capacity of the fecal microbiota and to compare to fucose. In batch fermentations of fecal microbiota collected from 17 donor samples, fucose promoted the production of propionate while no consistent effect was observed for commercial fucoidan and Fucus vesiculosus extract prepared in this study containing laminarin and fucoidan. H2S production was detected under all tested conditions, and levels were significantly lower in the presence of fucose in a dose-dependent manner. The addition of high fucose levels led to higher relative abundance of microbial 1,2-PD and lactate cross-feeders. Our results highlight that fucose and not fucoidan addition impacted fermentation capacity and increased the proportions of propionate and butyrate, which allows for precise modulation of intestinal microbiota activity.

Quality analysis of publicly available information about hypoplastic left heart syndrome.

PURPOSE: Publicly available health information is increasingly important for patients and their families. While the average US citizen reads at an 8th-grade level, electronic educational materials for patients and families are often advanced. We assessed the quality and readability of publicly available resources regarding hypoplastic left heart syndrome (HLHS). METHODS: We queried four search engines for "hypoplastic left heart syndrome", "HLHS", and "hypoplastic left ventricle". The top 30 websites from searches on Google, Yahoo!, Bing, and Dogpile were combined into a single list. Duplicates, commercial websites, physician-oriented resources, disability websites, and broken links were removed. Websites were graded for accountability, content, interactivity, and structure using a two-reviewer system. Nonparametric analysis of variance was performed. RESULTS: Fifty-two websites were analysed. Inter-rater agreement was high (Kappa = 0.874). Website types included 35 hospital/healthcare organisation (67.3%), 12 open access (23.1%), 4 governmental agency (7.7%), and 1 professional medical society (1.9%). Median total score was 19 of 39 (interquartile range = 15.8-25.3): accountability 5.5 of 17 (interquartile range = 2.0-9.3), content 8 of 12 (interquartile range = 6.4-10.0), interactivity 2 of 6 (interquartile range = 2.0-3.0), and structure 3 of 4 (interquartile range = 2.8-4.0). Accountability was low with 32.7% (n = 17) of sites disclosing authorship and 26.9% (n = 14) citing sources. Forty-two percent (n = 22) of websites were available in Spanish. Total score varied by website type (p = 0.03), with open access sites scoring highest (median = 26.5; interquartile range = 20.5-28.6) and hospital/healthcare organisation websites scoring lowest (median = 17.5; interquartile range = 13.5-21.5). Score differences were driven by differences in accountability (p = 0.001) - content scores were similar between groups (p = 0.25). Overall readability was low, with median Flesch-Kincaid Grade Level of 11th grade (interquartile range = 10th-12th grade). CONCLUSIONS: Our evaluation of popular websites about HLHS identifies multiple opportunities for improvement, including increasing accountability by disclosing authorship and citing sources, enhancing readability by providing material that is understandable to readers with the full spectrum of educational background, and providing information in languages besides English, all of which would enhance health equity.

Preparation and characterization of self-standing biofilms from compatible pectin/starch blends: Effect of pectin structure.

Pectin structure-miscibility-functionality relationships in starch films remain unknown. In this study, five citrus pectins (CPs) with 17 to 63 % of degree of methyl esterification (DM) and sugar beet pectin (SBP, rich in acetyl moieties and rhamnogalacturonan-I domains) were investigated for composition and structure and, further, blended with pea starch (3:1 starch-pectin weight ratio) to fabricate self-standing films. The incorporation of pectin resulted in a two- to three-fold increase in tensile strength and Young's modulus (up to 52.2 and 1837 MPa, respectively, using CP with low DM) without compromising elongation at break. Starch-SBP films presented the lowest strength among pectin films. Lower film moisture and water vapor permeability were attained with CP of high DM, or with SBP, whereas surface wettability was explained by counteracting factors affecting film compositional heterogeneity. Films made with high methoxyl CP, or with SBP, showed lower overall H-bonding (FTIR) and starch crystallinity (XRD). A DM above 57 % negatively affected the mixing and interfacial adhesion of pectin with starch, as shown by Attenuated Total Reflection-FTIR imaging. Pectins with the lowest purity, presumably with the greatest content in xyloglucan, as suggested by HPAEC, presented ~20 % higher elongation at break than the other films.

Untargeted screening and in silico toxicity assessment of semi- and non-volatile compounds migrating from polysaccharide-based food contact materials.

The chemical safety of representative polysaccharide films made with pea starch, organocatalytic acetylated pea starch and pectin was investigated at different migration conditions (20 °C/10 days, 70 °C/2 h) using two official simulants signifying hydrophilic (simulant A, 10% ethanol) or lipophilic (simulant D1, 50% ethanol) foods. Migrating semi-volatile and non-volatile compounds were identified and semi-quantified by ultra-high performance liquid chromatography-trap ion mobility time-of-flight mass spectrometry (UHPLC-TIMS-TOF-MS/MS), whereas their toxicity was evaluated by in silico models based on qualitative structure activity (QSAR). Physicochemical analysis revealed polymer wash-off into the simulants. Migration testing at 70 °C for 2 h using simulant D1 resulted in detectable concentrations of glycerol (≤72.1 mg/kg), monoacetylated maltose (≤6.5 mg/kg), and dibutyl phthalate (DBP) (≤0.5 mg/kg, compliant with the existing legislative migration limits) in samples containing acetylated starch. Migrating 3-ß-galactopyranosyl glucose (≤8.9 mg/kg) and 2,5-diketo-d-gluconic acid (≤4.9 mg/kg) were detected at 20 °C/10 days. In-silico toxicity emphasized no significant toxicity and categorized organocatalytic acetylated pea starch of no safety concern.

Prevalence of immune-related adverse events and anti-tumor efficacy in advanced/metastatic urothelial carcinoma following immune-checkpoint inhibitor treatment.

PURPOSE: We evaluated the prevalence of immune-related adverse events and anti-tumor efficacy in advanced/metastatic urothelial carcinoma following immune-checkpoint inhibitors (ICIs) treatment. METHODS: We conducted a multicenter retrospective study of patients with advanced/metastatic urothelial carcinoma treated with ICIs in four Spanish institutions. irAEs were classified using Common Terminology Criteria for Adverse Event (CTCAE) v.5.0 guidelines. The primary endpoint was overall survival (OS). Other endpoints were overall response rate (ORR) and progression-free survival (PFS). irAEs were evaluated as a time-dependent covariate to avoid immortal time bias. RESULTS: A total of 114 patients were treated with ICIs between May 2013 and May 2019, 105 (92%) of whom received ICIs as monotherapy. irAEs of any grade were experienced in 56 (49%) patients and 21 (18%) patients had grade ≥ 3 toxicity. The most frequent irAEs were gastrointestinal and dermatological toxicities, reported in 25 (22%) and 20 (17%) patients, respectively. Patients with grade 1-2 irAEs had significantly longer OS compared to those without grade 1-2 irAEs (median 18.2 vs. 8.7 months, HR = 0.61 [95% CI 0.39-0.95], p = 0.03). No association with efficacy was observed for patients with grade ≥ 3 irAEs. No difference in PFS was observed after adjusting for the immortal time bias. ORR was higher in patients who developed irAEs (48% vs 17%, p < 0.001). CONCLUSIONS: Our findings suggest that development of irAEs was associated with higher ORR, and patients who developed grade 1-2 irAEs had longer OS. Prospective studies are necessary to confirm our findings.

Organocatalytic acetylation of pea starch: Effect of alkanoyl and tartaryl groups on starch acetate performance.

Organocatalytic acetylation of pea starch was systematically optimized using tartaric acid as catalyst. The effect of the degree of substitution with alkanoyl (DSacyl) and tartaryl groups (DStar) on thermal and moisture resistivity, and film-forming properties was investigated. Pea starch with DSacyl from 0.03 to 2.8 was successfully developed at more efficient reaction rates than acetylated maize starch. Nevertheless, longer reaction time resulted in granule surface roughness, loss of birefringence, hydrolytic degradation, and a DStar up to 0.5. Solid-state 13C NMR and SEC-MALS-RI suggested that tartaryl groups formed crosslinked di-starch tartrate. Acetylation increased the hydrophobicity, degradation temperature (by ~17 %), and glass transition temperature (by up to ~38 %) of pea starch. The use of organocatalytically-acetylated pea starch with DSacyl ≤ 0.39 generated starch-based biofilms with higher tensile and water barrier properties. Nevertheless, at higher DS, the incompatibility between highly acetylated and native pea starches resulted in a heterogenous/microporous structure that worsened film properties.

Identification and analyses of the chemical composition of a naturally occurring albino mutant chanterelle.

White chanterelles (Basidiomycota), lacking the orange pigments and apricot-like odour of typical chanterelles, were found recently in the Canadian provinces of Québec (QC) and Newfoundland & Labrador (NL). Our phylogenetic analyses confirmed the identification of all white chanterelles from NL and QC as Cantharellus enelensis; we name these forma acolodorus. We characterized carotenoid pigments, lipids, phenolics, and volatile compounds in these and related chanterelles. White mutants of C. enelensis lacked detectable ß-carotene, confirmed to be the primary pigment of wild-type, golden-orange individuals, and could also be distinguished by their profiles of fatty acids and phenolic acids, and by the ketone and terpene composition of their volatiles. We detected single base substitutions in the phytoene desaturase (Al-1) and phytoene synthase (Al-2) genes of the white mutant, which are predicted to result in altered amino acids in their gene products and may be responsible for the loss of ß-carotene synthesis in that form.

Effects of pH and Temperature on Water under Pressurized Conditions in the Extraction of Nutraceuticals from Chaga (Inonotus obliquus) Mushroom.

Currently, there is increased interest in finding appropriate food-grade green extraction systems capable of extracting these bioactive compounds from dietary mushrooms for applications in various food, pharmacological, or nutraceutical formulations. Herein, we evaluated a modified Swiss water process (SWP) method using alkaline and acidic pH at low and high temperature under pressurized conditions as a suitable green food grade solvent to obtained extracts enriched with myco-nutrients (dietary phenolics, total antioxidants (TAA), vitamins, and minerals) from Chaga. Ultra-high performance liquid chromatography coupled to high resolution accurate mass tandem mass spectrometry (UHPLC-HRAMS-MS/MS) was used to assess the phenolic compounds and vitamin levels in the extracts, while inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the mineral contents. Over 20 phenolic compounds were quantitatively evaluated in the extracts and the highest total phenolic content (TPC) and total antioxidant activity (TAA) was observed at pH 11.5 at 100 °C. The most abundant phenolic compounds present in Chaga extracts included phenolic acids such as protocatechuic acid 4-glucoside (0.7-1.08 µg/mL), syringic acid (0.62-1.18 µg/mL), and myricetin (0.68-1.3 µg/mL). Vitamins are being reported for the first time in Chaga. Not only, a strong correlation was found for TPC with TAA (r-0.8, <0.0001), but also, with individual phenolics (i.e., Salicylic acid), lipophilic antioxidant activity (LAA), and total antioxidant minerals (TAM). pH 2.5 at 100 °C treatment shows superior effects in extracting the B vitamins whereas pH 2.5 at 60 and 100 °C treatments were outstanding for extraction of total fat-soluble vitamins. Vitamin E content was the highest for the fat-soluble vitamins in the Chaga extract under acidic pH (2.5) and high temp. (100 °C) and ranges between 50 to 175 µg/100 g Chaga. Antioxidant minerals ranged from 85.94 µg/g (pH7 at 100 °C) to 113.86 µg/g DW (pH2.5 at 100 °C). High temperature 100 °C and a pH of 2.5 or 9.5. The treatment of pH 11.5 at 100 °C was the most useful for recovering phenolics and antioxidants from Chaga including several phenolic compounds reported for the first time in Chaga. SWP is being proposed herein for the first time as a novel, green food-grade solvent system for the extraction of myco-nutrients from Chaga and have potential applications as a suitable approach to extract nutrients from other matrices. Chaga extracts enriched with bioactive myconutrients and antioxidants may be suitable for further use or applications in the food and nutraceutical industries.

Development and assessment of GC/MS and HPAEC/PAD methodologies for the quantification of α-galacto-oligosaccharides (GOS) in dry beans (Phaseolus vulgaris).

The quantification of α-Galacto-oligosaccharides (GOS) in beans has been increasingly approached through different methodologies. However, reported GOS contents revealed up to 8-times disparity, which cannot be only attributed to the bean cultivar and underlines the need of using validated analytical methodologies. This study aimed to optimize and validate the extraction of the most abundant GOS found in beans, namely raffinose, stachyose and verbascose, and comparatively assess their determination by High-Performance Anion Exchange Chromatography/Pulsed Amperometric Detector (HPAEC/PAD) and Gas Chromatography/Mass Spectrometry (GC/MS). Hot sonication followed by shaking with 70% ethanol resulted in excellent GOS extraction efficiencies (92.54-107.94%). GC/MS determination was more reliable than HPAEC/PAD, with limits of quantification of 4.48-224.31 mg/kg and intra/inter-day repeatabilities <10%. The analysis of six bean varieties proved the feasibility of the GC/MS methodology, displaying total GOS contents from 1453.07 ±â€¯169.31 to 2814.34 ±â€¯95.28 mg/100 g. Stachyose was significantly (p < 0.05) the main GOS in all samples.

Effects of beer based marinades on the plasmalogen content and composition of grilled ruminant meats.

Plasmalogens are important phospholipids essential for maintaining cardiovascular and brain health. Ruminant meats are excellent dietary sources of plasmalogens. Globally, grilling remains a popular technique for preparing meats. However, little is known concerning how marination affects retention and quality of plasmalogens in grilled ruminant meats. Here we present information on effects of two unfiltered beer-based marinades infused with herbs and spices on plasmalogens in grilled beef and moose meats. Although total plasmalogen contents of marinated grilled meats were lower compared to unmarinated controls; compositionally, wheat ale- and India session ale-based marinades retained higher levels of PUFA plasmalogen PC (phosphatidylcholine) and PE (phosphatidylethanolamine) species enriched with ω3 and ω6 fatty acids in grilled moose meats. In grilled beef, significantly higher levels of plasmalogen PC species enriched with monounsaturated fatty acids (MUFA) and PUFA were retained by Wheat ale-based marinade. Furthermore, strong positive correlations were observed between antioxidants, polyphenols, oxygenated terpenes and plasmalogens retained in the marinated grilled meats which contrasted negative correlations with total oxidation status of the marinated grilled meats. These findings appear to suggest that the phenolics, oxygenated terpenes and antioxidants present in the beer-based marinades preserved these plasmalogens in marinated meats against degradation during grilling. In view of the benefits associated with plasmalogens and essential fatty acid consumption, marination of beef and moose meats with unfiltered beer-based marinades could be useful for retaining MUFA and PUFA-enriched plasmalogens, as well as preserving the nutritional quality of grilled beef and moose meats.

Assessing unfiltered beer-based marinades effects on ether and ester linked phosphatidylcholines and phosphatidylethanolamines in grilled beef and moose meat.

Ruminant meats contain ester and ether-linked phosphatidylcholines-(PC) and phosphatidylethanolamines-(PE) enriched with ω3 and ω6 polyunsaturated fatty acids-(PUFA) essential for human health and nutrition. Oxidative degradation of these lipids during grilling compromises meat quality and safety. The effect of marinades containing unfiltered session ales, herbs and spices on these lipids in grilled beef and moose meat was investigated in current study. Marination preserved (P < 0.05) ester and ether linked PUFA-enriched PC and PE in moose, and PUFA-enriched ether PC and diacyl PE in beef against oxidative degradation. Furthermore, India ale-based marinated meats retained higher (P < 0.05) PUFA-enriched lysophosphatidylcholines-(LPC) and lysophosphatidylethanolamines-(LPE) compared to Wheat ale-based marinated meats. The preserved PUFA-enriched lipids were positively correlated with phenolics, oxygenated terpenes, and antioxidants present in the marinades, and negatively correlated to oxidation status. These findings appear to suggest that unfiltered beer-based marination could be a useful precooking technique to increase dietary access and consumption of essential fatty acids while preserving grilled meat nutritional quality and safety.

[New paradigms in the second line treatment for advanced and metastatic urothelial carcinoma.] / Nuevos paradigmas en el tratamiento de 2ª línea del cáncer vesical músculo invasivo metastásico.

Until 2016, the treatment options for patients with urothelial carcinoma who had progressed to first line treatment were limited. Vinflunine has been the only approved treatment in Europe for this indication. The only alternatives in these patients were clinical trials or other chemotherapies with low efficacy and high toxicity. The last couple of years, three immune-checkpoint inhibitors have been approved in Europe (pembrolizumab, atezolizumab and nivolumab) and five in USA (pembrolizumab, atezolizumab, nivolumab, durvalumaband avelumab), showing improved overall survival (OS), response rate (ORR) and tolerance. Recently, the FDA has approved two new treatments based on the results from the phase II trials. Erdafitinib, the first anti-FGFR treatment in patients with mutations/fusions in FGFR2/3 showed an ORR of 40% and an OS of 13,8 months. Likewise, enfortumab-vedotin, an antibody conjugates, was approved by the FDA based on the phase II trial results. Enfortumab-vedotin presented an ORR of 44%(12% of complete response) and an OS of 11,7 months. Other antiFGFR, antibody conjugates and immunotherapy combinations are in development, with promising results that need to be further confirmed in order to be approved. As a result, the landscape of urothelial canceris rapidly evolving. However, the challenge of individualizing and sequencing treatments remains.

Hasta el año 2016, las opciones de tratamiento para los pacientes con carcinoma urotelial avanzado que progresaban durante o después del tratamiento de primera línea eran limitadas, siendo vinflunina el único fármaco aprobado en Europa en esta indicación. Las únicas alternativas eran la inclusión en ensayo clínico o el tratamiento quimioterápico fuera de indicación con eficacia limitada y alta toxicidad. En los últimos años se han aprobado tres fármacos inmunoterápicos en Europa (pembrolizumab, atezolizumab y nivolumab) y cincoen EEUU (pembrolizumab, atezolizumab, nivolumab,durvalumab y avelumab), logrando mejoras en términos de supervivencia global (SG), tasa de respuestas (TR) y perfil de tolerabilidad. Recientemente, la FDA también ha aprobado dos fármacos muy prometedores en basea sus resultados en estudios fase II. Erdafitinib, el primer fármaco anti-diana para pacientes con alteraciones en FGFR 2/3, con una TR de 40% y una SG de 13,8 meses, y enfortumab-vedotin, un anticuerpo conjugado, con una TR de 44%, 12% respuestas completas (RC) y SG de11,7 meses, ocupan hoy un lugar en el panorama terapéutico anglosajón. Hay otros tratamientos antiFGFR, anticuerpos conjugados y combinaciones de inmunoterapia con fármacos que potencian su efecto con resultadosprometedores en estudios preliminares, pero que se deben confirmar en estudios más avanzados para suaprobación. Por todo ello, el tratamiento del carcinoma urotelial avanzado está sufriendo cambios importantes, permaneciendo inalterado el reto de la individualización del tratamiento y la secuencia terapéutica.

Nuevos paradigmas en el tratamiento de 2ª línea del cáncer vesical músculo invasivo metastásico / New paradigms in the second line treatment for advanced and metastatic urothelial carcinoma

Hasta el año 2016, las opciones de tratamiento para los pacientes con carcinoma urotelial avanzado que progresaban durante o después del tratamiento de primera línea eran limitadas, siendo vinflunina el único fármaco aprobado en Europa en esta indicación. Las únicas alternativas eran la inclusión en ensayo clínico o el tratamiento quimioterápico fuera de indicación con eficacia limitada y alta toxicidad. En los últimos años se han aprobado tres fármacos inmunoterápicos en Europa (pembrolizumab, atezolizumab y nivolumab) y cinco en EEUU (pembrolizumab, atezolizumab, nivolumab, durvalumab y avelumab), logrando mejoras en términos de supervivencia global (SG), tasa de respuestas (TR) y perfil de tolerabilidad. Recientemente, la FDA también ha aprobado dos fármacos muy prometedores en base a sus resultados en estudios fase II. Erdafitinib, el primer fármaco anti-diana para pacientes con alteraciones en FGFR 2/3, con una TR de 40% y una SG de 13,8 meses, y enfortumab-vedotin, un anticuerpo conjugado, con una TR de 44%, 12% respuestas completas (RC) y SG de 11,7 meses, ocupan hoy un lugar en el panorama terapéutico anglosajón. Hay otros tratamientos antiFGFR, anticuerpos conjugados y combinaciones de inmunoterapia con fármacos que potencian su efecto con resultados prometedores en estudios preliminares, pero que se deben confirmar en estudios más avanzados para su aprobación. Por todo ello, el tratamiento del carcinoma urotelial avanzado está sufriendo cambios importantes, permaneciendo inalterado el reto de la individualización del tratamiento y la secuencia terapéutica

Until 2016, the treatment options for patients with urothelial carcinoma who had progressed to first line treatment were limited. Vinflunine has been the only approved treatment in Europe for this indication. The only alternatives in these patients were clinical trials or other chemotherapies with low efficacy and high toxicity. The last couple of years, three immune-checkpoint inhibitors have been approved in Europe (pembrolizumab, atezolizumab and nivolumab) and five in USA (pembrolizumab, atezolizumab, nivolumab, durvalumab and avelumab), showing improved overall survival (OS), response rate (ORR) and tolerance. Recently, the FDA has approved two new treatments based on the results from the phase II trials. Erdafitinib, the first anti-FGFR treatment in patients with mutations/fusions in FGFR2/3 showed an ORR of 40% and an OS of 13,8 months. Likewise, enfortumab-vedotin, an antibody conjugates, was approved by the FDA based on the phase II trial results. Enfortumab-vedotin presented an ORR of 44% (12% of complete response) and an OS of 11,7 months. Other antiFGFR, antibody conjugates and immunotherapy combinations are in development, with promising results that need to be further confirmed in order to be approved. As a result, the landscape of urothelial cancer is rapidly evolving. However, the challenge of individualizing and sequencing treatments remains

Dataset showing the relationship between terpenes, antioxidants and polyphenols in protecting ester and ether linked glycerophospholipids of grilled beef and moose meat marinated with unfiltered beer from oxidation.

This article presents the associated data set in the research article entitled "Assessing beer-based marinades effects on ether and ester linked phosphatidylcholines and phosphatidylethanolamines in grilled beef and moose meat" published in Meat Science [1], demonstrating the use of unfiltered beer-based marinades in improving the nutritional quality of grilled ruminant meat by suppressing the degradation of health-promoting ester and ether-linked PC and PE the most predominant glycerophospholipids (GPL) in meat. High throughput lipidomics analysis was conducted using high-resolution accurate mass tandem mass spectrometry (UHPLC-HRAMS/MS-MS) to profile the meat lipids following marination and grilling. The marinades were composed of a combination of unfiltered beers, fruits, herbs and spices. The data presented show the retention levels of ether as well as ester linked PC and PE molecular species; Pearson's correlations for the associations between antioxidants, phenolics, volatile oxygenated terpenes, oxidation status and preserved phospholipid species in the marinated grilled meats. There are many studies demonstrating cooking effects on fatty acid composition of meat phospholipids in the literature. However, information on how marination and grilling affects intact ether and ester linked PC and PE composition in grilled ruminant meats is limited. As such, this dataset provides useful information on the preservation of ruminant meat ester and ether-linked glycerophospholipid composition following marination with unfiltered beer-based marinades and meat preparation via grilling. Specifically, this data demonstrate the preservation of ether and ester linked PC and PE enriched with essential ω3 and ω6 fatty acids from degradation during grilling. For additional insights see [1] DOI: 10.1016/j.meatsci.2020.108271.