Risk of endometrial cancer after RRSO in BRCA 1/2 carriers: a multicentre cohort study.

OBJECTIVE: To know the risk of endometrial cancer (EC) in a population of women with BRCA 1/2 pathogenic or likely pathogenic variants after risk-reducing salpingo-oophorectomy (RRSO). METHODS: The study cohort included data from 857 women with BRCA mutations who underwent RRSO visited four hospitals in Catalonia, Spain, from January 1, 1999 to April 30, 2019. Standardized incidence ratio (SIR) of EC was calculated in these patients using data from a regional population-based cancer registry. RESULTS: After RRSO, eight cases of EC were identified. Four in BRCA 1 carriers and four in BRCA2 carriers. The expected number of cases of EC was 3.67 cases, with a SIR of 2.18 and a 95% CI (0.93-3.95). CONCLUSIONS: In our cohort, the risk of EC in BRCA1/2 carriers after RRSO is not greater than expected. Hysterectomy is not routinely recommended for these patients.

Blue prescription: A pilot study of health benefits for oncological patients of a short program of activities involving the sea.

Performing outdoor activities in blue spaces can help improve human health and mental well-being by reducing stress and promoting social relationships. The number of people surviving cancer has increased globally to experience this disease as a life-changing and chronic condition with physical and psychosocial symptoms that have negative impacts on their quality of life. While there has been a growth of programs in green spaces to meet the needs of cancer patients, such as follow-up post-treatment care, support groups and physical activity programs, very few studies have examined the effects of activities involving the sea for the health and well-being of oncology patients. This is the first study to evaluate whether different outdoor activities in blue spaces can benefit oncological patients' physical and mental health using smartwatches, sphygmomanometers and Profile of Mood States (POMS) questionnaires. We assessed changes in blood pressure, heart rate, sleep quality and mental health of 16 patients after twelve sessions of three different activities (walking, beach and snorkelling) and four sessions of a control activity. While no significant differences between activities were observed in terms of the data gathered by the smartwatches, a gradient of positive results for human mental health was observed towards exposure to a blue space, assessed through POMS questionnaires. Results show that exposure to blue spaces contributes to tension and anger reduction and improves the vigour mood state of oncology patients. No significant increases in patients' heart rate were recorded after the beach and snorkelling activities, with results similar to the control activity, suggesting that the contribution may be to participants' relaxation.

Anti-inflammatory effects of naringenin 8-sulphonate from Parinari excelsa Sabine stem bark and its semi-synthetic derivatives.

The inflammatory response is a vital mechanism for repairing damage induced by aberrant health states or external insults; however, persistent activation can be linked to numerous chronic diseases. The nuclear factor kappa ß (NF-κB) inflammatory pathway and its associated mediators have emerged as critical targets for therapeutic interventions aimed at modulating inflammation, necessitating ongoing drug development. Previous studies have reported the inhibitory effect of a hydroethanol extract derived from Parinari excelsa Sabine (Chrysobalanaceae) on tumour necrosis factor-alpha (TNF-α), but the phytoconstituents and mechanisms of action remained elusive. The primary objective of this study was to elucidate the phytochemical composition of P. excelsa stem bark and its role in the mechanisms underpinning its biological activity. Two compounds were detected via HPLC-DAD-ESI(Ion Trap)-MS2 analysis. The predominant compound was isolated and identified as naringenin-8-sulphonate (1), while the identity of the second compound (compound 2) could not be determined. Both compound 1 and the extract were assessed for anti-inflammatory properties using a cell-based inflammation model, in which THP-1-derived macrophages were stimulated with LPS to examine the treatments' effects on various stages of the NF-κB pathway. Compound 1, whose biological activity is reported here for the first time, demonstrated inhibition of NF-κB activity, reduction in interleukin 6 (IL-6), TNF-α, and interleukin 1 beta (IL-1ß) production, as well as a decrease in p65 nuclear translocation in THP-1 cells, thus highlighting the potential role of sulphur substituents in the activity of naringenin (3). To explore the influence of sulphation on the anti-inflammatory properties of naringenin derivatives, we synthesized naringenin-4'-O-sulphate (4) and naringenin-7-O-sulphate (5) and evaluated their anti-inflammatory effects. Naringenin derivatives 4 and 5 did not display potent anti-inflammatory activities; however, compound 4 reduced IL-1ß production, and compound 5 diminished p65 translocation, with both exhibiting the capacity to inhibit TNF-α and IL-6 production. Collectively, the findings demonstrated that the P. excelsa extract was more efficacious than all tested compounds, while providing insights into the role of sulphation in the anti-inflammatory activity of naringenin derivatives.

Kitul, a food plant with antidiabetic-like effects: Reduction of intracellular reactive species in glucose-stimulated RIN-5F pancreatic ß-cells and mitigation of pro-inflammatory mediators in activated RAW 264.7 macrophages.

Kitul (Caryota urens L.) inflorescences are broadly used for sweet sap production in Asian countries and Kitul food products are known as being suitable for diabetic patients. Considering the strong ability to inhibit α-glucosidase, we hypothesize that kitul antidiabetic properties might also involve the modulation of inflammatory pathways and hyperglycaemia-induced oxidative damage. Hence, the effects of an inflorescence's methanol extract were investigated in glucose-stimulated pancreatic cells (RIN-5F) and LPS-stimulated RAW 264.7 macrophages. The extract reduced the overproduction of intracellular reactive species in pancreatic cells and also NO, L-citrulline and IL-6 levels in LPS-stimulated RAW 264.7 macrophages. Inhibition of 5-lipoxygenase (IC50 = 166.1 µg/mL) through an uncompetitive manner was also recorded upon treatment with C. urens inflorescences extract. The phenolic profile of the inflorescences was characterized by HPLC-DAD, six hydroxycinnamic acids being identified and quantified. Overall, our data provide additional evidence on the pleiotropic mechanisms of Kitul inflorescences as an antidiabetic agent.

Ability of a Polyphenol-Rich Nutraceutical to Reduce Central Nervous System Lipid Peroxidation by Analysis of Oxylipins in Urine: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Isoprostanes (IsoPs) are lipid peroxidation biomarkers that reveal the oxidative status of the organism without specifying which organs or tissues it occurs in. Similar compounds have recently been identified that can assess central nervous system (CNS) lipid peroxidation status, usually oxidated by reactive oxygen species. These compounds are the neuroprostanes (NeuroPs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the F2t-dihomo-isoprotanes derived from adrenic acid (AdA). The aim of the present investigation was to evaluate whether the long-term nutraceutical consumption of high polyphenolic contents (600 mg) from fruits (such as berries) and vegetables shows efficacy against CNS lipid peroxidation in urine biomarkers. A total of 92 subjects (47 females, 45 males, age 34 ± 11 years old, weight 73.10 ± 14.29 kg, height 1.72 ± 9 cm, body mass index (BMI) 24.40 ± 3.43 kg/m2) completed a randomized, cross-over, double-blind study after an intervention of two periods of 16 weeks consuming either extract (EXT) or placebo (PLA) separated by a 4-week washout period. The results showed significant reductions in three AdA-derived metabolites, namely, 17-epi-17-F2t-dihomo-IsoPs (Δ -1.65 ng/mL; p < 0.001), 17-F2t-dihomo-IsoPs (Δ -0.17 ng/mL; p < 0.015), and ent-7(RS)-7-F2t-dihomo-IsoPs (Δ -1.97 ng/mL; p < 0.001), and one DHA-derived metabolite, namely, 4-F4t-NeuroP (Δ -7.94 ng/mL; p < 0.001), after EXT consumption, which was not observed after PLA consumption. These data seem to show the effectiveness of the extract for preventing CNS lipid peroxidation, as determined by measurements of oxylipins in urine through Ultra-High-Performance Liquid Chromatography triple quadrupole tandem mass spectrometry (UHPLC-QqQ-ESI-MS/MS).

Allophylus africanus Stem Bark Extract Modulates the Mitochondrial Apoptotic Pathway in Human Stomach Cancer Cells.

The present work aimed to detail the mechanisms elicited by Allophylus africanus P. Beauv. stem bark extract in human stomach cancer cells and to identify the bioactives underlying the cytotoxicity. MTT reduction and LDH leakage assays allowed characterizing the cytotoxic effects in AGS cells, which were further detailed by morphological analysis using phalloidin and Hoechst 33258. Proapoptotic mechanisms were elucidated through a mitochondrial membrane potential assay and by assessing the impact upon the activity of caspase-9 and -3. The extract displayed selective cytotoxicity against AGS cells. The absence of plasma membrane permeabilization, along with apoptotic body formation, suggested that pro-apoptotic effects triggered cell death. Intrinsic apoptosis pathway activation was verified, as mitochondrial membrane potential decrease and activation of caspase-9 and -3 were observed. HPLC-DAD profiling enabled the identification of two apigenin-di-C-glycosides, vicenin-2 (1) and apigenin-6-C-hexoside-8-C-pentoside (3), as well as three mono-C-glycosides-O-glycosylated derivatives, apigenin-7-O-hexoside-8-C-hexoside (2), apigenin-8-C-(2-rhamnosyl)hexoside (4) and apigenin-6-C-(2-rhamnosyl)hexoside (5). Isovitexin-2″-O-rhamnoside (5) is the main constituent, accounting for nearly 40% of the total quantifiable flavonoid content. Our results allowed us to establish the relationship between the presence of vicenin-2 and other apigenin derivatives with the contribution to the cytotoxic effects on the presented AGS cells. Our findings attest the anticancer potential of A. africanus stem bark against gastric adenocarcinoma, calling for studies to develop herbal-based products and/or the use of apigenin derivatives in chemotherapeutic drug development.

Carvacrol and HP-ß-Cyclodextrin Complexes: Extensive Characterization and Potential Cytotoxic Effect in Human Colorectal Carcinoma Cells.

The aim of this study was to obtain solid carvacrol-cyclodextrin (CD) complexes for use in the pharmaceutical industry. To this end, the complexation of carvacrol at different pH values was studied in detail, to determine the type of CD and the reaction environment that supported the highest amount of encapsulated carvacrol. Evidence of the capability of hydroxypropyl-ß-cyclodextrins (HP-ß-CD) to form inclusion complexes with carvacrol (KC = 5042 ± 176 L mol-1) and more high complexation efficiency (2.824) was demonstrated for HP-ß-CDs using two different energy sources, ultrasound (US) (KC = 8129 ± 194 L mol-1 24 h) and microwave irradiation (MWI) (KC = 6909 ± 161 L mol-1), followed by spraying the resulting solution in a spray dryer. To confirm complex formation, the complexes were characterized using various instrumental methods to corroborate the carvacrol incorporation into the hydrophobic cavity of HP-ß-CD. The obtained carvacrol solid complexes were analyzed by 1H nuclear magnetic resonance (1H-NMR) and 2D nuclear magnetic resonance (ROSEY), differential scanning calorimetry (DSC), thermogravimetric analysis (TG) and Fourier transform infrared spectroscopy (FTIR) characterization. The structures of the resulting complexes were also characterized by molecular modeling. Furthermore, 1 mM HP-ß-CD-carvacrol complex has been shown to reduce cell proliferation in HCT-116 colorectal cancer cells by 43%, much more than in a healthy lung fibroblast MRC-5 cell line (11%).

Dietary antioxidant intake is inversely associated with 2,3-dinor oxylipin metabolites, the major excreted oxylipins in overweight and obese subjects.

Cardiometabolic disease risk factors, including obesity, insulin resistance, high blood pressure, and dyslipidemia, are associated with elevated oxidative stress biomarkers like oxylipins. Increased adiposity by itself induces various isomers of this oxidized lipid family, while dietary polyphenols show benefits in its regulation. Previously, we showed that specific co-abundant microorganisms characterized the gut microbiota of Colombians and associated differentially with diet, lifestyle, obesity, and cardiometabolic health status, which led us to hypothesize that urinary oxylipins would reflect the intensity of oxidative metabolism linked to gut microbiota dysbiosis. Thus, we selected a convenience sample of 105 participants (age: 40.2 ± 11.9 years, 47.6% women), grouped according to microbiota, cardiometabolic health status, and body mass index (BMI); and evaluated 33 urinary oxylipins by HPLC-QqQ-MS/MS (e.g., isoprostanes, prostaglandins, and metabolites), paired with anthropometry and blood chemistry information and dietary antioxidants estimated from a 24-h food recall. In general, oxylipins did not show differences among individuals who differed in gut microbiota. While the unmetabolized oxylipin levels were not associated with BMI, the total content of oxylipin metabolites was highest in obese and cardiometabolically abnormal subjects (e.g., insulin resistant), mainly by prostaglandin-D (2,3-dinor-11ß-PGF2α) and 15-F2t-IsoPs (2,3-dinor-15-F2t-IsoP and 2,3-dinor-15-epi-15-F2t-IsoP) metabolites. The total polyphenol intake in this cohort was 1070 ± 627 mg/day. After adjusting for body weight, the polyphenol intake was significantly higher in lean than overweight and showed an inverse association with dinor-oxylipin levels in principal component analysis. These results suggest that the 2,3-dinor-oxylipins could be more specific biomarkers associated with BMI than their parent oxylipins and that are sensitive to be regulated by dietary antioxidants.

Anti-Inflammatory and Antioxidant Capacity of a Fruit and Vegetable-Based Nutraceutical Measured by Urinary Oxylipin Concentration in a Healthy Population: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Oxylipins, lipid biomarkers of inflammation are considered the gold standard method to evaluate the inflammatory and antioxidant status. The aim of the present study was to investigate whether the administration of a polyphenolic extract shot in the form of a nutraceutical was able to reduce inflammation, measured in urine markers. Ninety-two participants (45 males, 47 females, age 34 ± 11 years, weight 73.10 ± 14.29 kg, height 1.72 ± 9 cm, BMI 24.40 ± 3.43 kg/m2) completed the study after an intervention of two 16-week periods consuming extract or placebo separated by a 4-week washout period. The results showed significant differences in terms of reduction of different pro-inflammatory oxylipins (15-keto-PGF2α (from 0.90 ± 0.25 ng/mL to 0.74 ± 0.19 ng/mL p < 0.05), ent-PGF2α (from 1.59 ± 0.37 ng/mL to 1.44 ± 0.32 ng/mL p < 0.05), 2,3-dinor-15-F2t-Isop) (from 1.17 ± 0.35 ng/mL to 1.02 ± 0.27 ng/mL p < 0.05), in total oxylipins count (from 8.03 ± 1.86 ng/mL to 7.25 ± 1.23 ng/mL p < 0.05), and increase in PGE2 (from 1.02 ± 0.38 ng/mL to 1.26 ± 0.38 ng/mL p < 0.05) which has an anti-inflammatory character, after extract consumption compared to placebo. The available data seem to indicate that long-term consumption of a nutraceutical with high polyphenol content improves inflammation and oxidation parameters measured in urine, through UHPLC-QqQ-ESI-MS/MS.

Using population-based data to evaluate the impact of adherence to endocrine therapy on survival in breast cancer through the web-application BreCanSurvPred.

We show how the use and interpretation of population-based cancer survival indicators can help oncologists talk with breast cancer (BC) patients about the relationship between their prognosis and their adherence to endocrine therapy (ET). The study population comprised a population-based cohort of estrogen receptor positive BC patients (N = 1268) diagnosed in Girona and Tarragona (Northeastern Spain) and classified according to HER2 status (+ / -), stage at diagnosis (I/II/III) and five-year cumulative adherence rate (adherent > 80%; non-adherent ≤ 80%). Cox regression analysis was performed to identify significant prognostic factors for overall survival, whereas relative survival (RS) was used to estimate the crude probability of death due to BC (PBC). Stage and adherence to ET were the significant factors for predicting all-cause mortality. Compared to stage I, risk of death increased in stage II (hazard ratio [HR] 2.24, 95% confidence interval [CI]: 1.51-3.30) and stage III (HR 5.11, 95% CI 3.46-7.51), and it decreased with adherence to ET (HR 0.57, 95% CI 0.41-0.59). PBC differences were higher in non-adherent patients compared to adherent ones and increased across stages: stage I: 6.61% (95% CI 0.05-13.20); stage II: 9.77% (95% CI 0.59-19.01), and stage III: 22.31% (95% CI 6.34-38.45). The age-adjusted survival curves derived from this modeling were implemented in the web application BreCanSurvPred ( https://pdocomputation.snpstats.net/BreCanSurvPred ). Web applications like BreCanSurvPred can help oncologists discuss the consequences of non-adherence to prescribed ET with patients.

HPLC-DAD-ESI/MSn and UHPLC-ESI/QTOF/MSn characterization of polyphenols in the leaves of Neocarya macrophylla (Sabine) Prance ex F. White and cytotoxicity to gastric carcinoma cells.

Among several extracts from species from Guinea-Bissauan flora, the hydroethanol extract obtained from the leaves of gingerbread plum (Neocarya macrophylla (Sabine) Prance ex F. White.) revealed to be one of the most cytotoxic towards human gastric AGS carcinoma cells. Considering the increasing use of N. macrophylla in the food industry and the abundant biomass of agricultural wastes being generated, the identification of phenolic bioactives has been attained by HPLC-DAD-ESI/MSn and UHPLC-ESI/QTOF/MSn. Twenty-seven phenolic constituents were identified for the first time in the monotypic genus Neosartorya, 5-O-caffeoylquinic acid being detected as the major constituent (4.90 ± 0.20 mg g-1 dry extract). While 15 flavan-3-ols derivatives were determined, the extract is predominantly characterized by the occurrence of quercetin, kaempferol, apigenin and chrysoeriol glycosides. Typical apoptotic changes in gastric adenocarcinoma AGS cells upon exposure to N. macrophylla leaf extract were observed. The apoptotic cell death is mediated by the activation of the mitochondrial pathway, as loss of mitochondrial membrane potential was detected, as well as increased caspase-9 and -3 activities. The industrial relevance of this plant material, along with the data presented here on the potential anticancer effects of N. macrophylla and the efficient extraction of phenolic bioactives using water and ethanol (GRAS substance), calls for further research on the leaves as a potential functional food and/or ingredient.

No Excess Mortality up to 10 Years in Early Stages of Breast Cancer in Women Adherent to Oral Endocrine Therapy: A Probabilistic Graphical Modeling Approach.

Breast cancer (BC) is globally the most frequent cancer in women. Adherence to endocrine therapy (ET) in hormone-receptor-positive BC patients is active and voluntary for the first five years after diagnosis. This study examines the impact of adherence to ET on 10-year excess mortality (EM) in patients diagnosed with Stages I to III BC (N = 2297). Since sample size is an issue for estimating age- and stage-specific survival indicators, we developed a method, ComSynSurData, for generating a large synthetic dataset (SynD) through probabilistic graphical modeling of the original cohort. We derived population-based survival indicators using a Bayesian relative survival model fitted to the SynD. Our modeling showed that hormone-receptor-positive BC patients diagnosed beyond 49 years of age at Stage I or beyond 59 years at Stage II do not have 10-year EM if they follow the prescribed ET regimen. This result calls for developing interventions to promote adherence to ET in patients with hormone receptor-positive BC and in turn improving cancer survival. The presented methodology here demonstrates the potential use of probabilistic graphical modeling for generating reliable synthetic datasets for validating population-based survival indicators when sample size is an issue.

Predicting Ovarian-Cancer Burden in Catalonia by 2030: An Age-Period-Cohort Modelling.

Ovarian cancer is the most lethal gynaecological cancer in very-high-human-development-index regions. Ovarian cancer incidence and mortality rates are estimated to globally rise by 2035, although incidence and mortality rates depend on the region and prevalence of the associated risk factors. The aim of this study is to assess changes in incidence and mortality of ovarian cancer in Catalonia by 2030. Bayesian autoregressive age-period-cohort models were used to predict the burden of OC incidence and mortality rates for the 2015-2030 period. Incidence and mortality rates of ovarian cancer are expected to decline in Catalonia by 2030 in women ≥ 45 years of age. A decrease in ovarian-cancer risk was observed with increasing year of birth, with a rebound in women born in the 1980s. A decrease in mortality was observed for the period of diagnosis and period of death. Nevertheless, ovarian-cancer mortality remains higher among older women compared to other age groups. Our study summarizes the most plausible scenario for ovarian-cancer changes in terms of incidence and mortality in Catalonia by 2030, which may be of interest from a public health perspective for policy implementation.

Ten-Year Probabilities of Death Due to Cancer and Cardiovascular Disease among Breast Cancer Patients Diagnosed in North-Eastern Spain.

Mortality from cardiovascular disease (CVD), second tumours, and other causes is of clinical interest in the long-term follow-up of breast cancer (BC) patients. Using a cohort of BC patients (N = 6758) from the cancer registries of Girona and Tarragona (north-eastern Spain), we studied the 10-year probabilities of death due to BC, other cancers, and CVD according to stage at diagnosis and hormone receptor (HR) status. Among the non-BC causes of death (N = 720), CVD (N = 218) surpassed other cancers (N = 196). The BC cohort presented a significantly higher risk of death due to endometrial and ovarian cancers than the general population. In Stage I, HR- patients showed a 1.72-fold higher probability of all-cause death and a 6.11-fold higher probability of breast cancer death than HR+ patients. In Stages II-III, the probability of CVD death (range 3.11% to 3.86%) surpassed that of other cancers (range 0.54% to 3.11%). In Stage IV patients, the probability of death from any cancer drove the mortality risk. Promoting screening and preventive measures in BC patients are warranted, since long-term control should encompass early detection of second neoplasms, ruling out the possibility of late recurrence. In patients diagnosed in Stages II-III at an older age, surveillance for preventing late cardiotoxicity is crucial.

Silibinin Suppresses Tumor Cell-Intrinsic Resistance to Nintedanib and Enhances Its Clinical Activity in Lung Cancer.

The anti-angiogenic agent nintedanib has been shown to prolong overall and progression-free survival in patients with advanced non-small-cell lung cancer (NSCLC) who progress after first-line platinum-based chemotherapy and second-line immunotherapy. Here, we explored the molecular basis and the clinical benefit of incorporating the STAT3 inhibitor silibinin-a flavonolignan extracted from milk thistle-into nintedanib-based schedules in advanced NSCLC. First, we assessed the nature of the tumoricidal interaction between nintedanib and silibinin and the underlying relevance of STAT3 activation in a panel of human NSCLC cell lines. NSCLC cells with poorer cytotoxic responses to nintedanib exhibited a persistent, nintedanib-unresponsive activated STAT3 state, and deactivation by co-treatment with silibinin promoted synergistic cytotoxicity. Second, we tested whether silibinin could impact the lysosomal sequestration of nintedanib, a lung cancer cell-intrinsic mechanism of nintedanib resistance. Silibinin partially, but significantly, reduced the massive lysosomal entrapment of nintedanib occurring in nintedanib-refractory NSCLC cells, augmenting the ability of nintedanib to reach its intracellular targets. Third, we conducted a retrospective, observational multicenter study to determine the efficacy of incorporating an oral nutraceutical product containing silibinin in patients with NSCLC receiving a nintedanib/docetaxel combination in second- and further-line settings (n = 59). Overall response rate, defined as the combined rates of complete and partial responses, was significantly higher in the study cohort receiving silibinin supplementation (55%) than in the control cohort (22%, p = 0.011). Silibinin therapy was associated with a significantly longer time to treatment failure in multivariate analysis (hazard ratio 0.43, p = 0.013), despite the lack of overall survival benefit (hazard ratio 0.63, p = 0.190). Molecular mechanisms dictating the cancer cell-intrinsic responsiveness to nintedanib, such as STAT3 activation and lysosomal trapping, are amenable to pharmacological intervention with silibinin. A prospective, powered clinical trial is warranted to confirm the clinical relevance of these findings in patients with advanced NSCLC.

Activation of caspase-3 in gastric adenocarcinoma AGS cells by Xylopia aethiopica (Dunal) A. Rich. fruit and characterization of its phenolic fingerprint by HPLC-DAD-ESI(Ion Trap)-MSn and UPLC-ESI-QTOF-MS2.

While the fruits of Xylopia aethiopica (Dunal) A. Rich. are important in African countries as a local trade product, their composition remains scarcely investigated. Phenolic fingerprint is herein delivered through HPLC-DAD-ESI(Ion Trap)-MSn and UPLC-ESI-QTOF-MS2 analysis, six cinnamoylquinic acid derivatives and twenty-four flavonoid glycosides being determined, chrysoeriol-7-O-glycosides being the main constituents. A cytotoxicity screening of twenty-eight hydroethanol extracts, obtained from a collection of Guinea-Bissauan plants, against A549 and AGS carcinoma cells, revealed the selective and potent effect towards AGS cells (IC50 = 151 × 10-3 g L-1), upon exposure to the extract from X. aethiopica fruits. Additional experiments demonstrated insignificant effect on LDH release at 151 × 10-3 g L-1, morphological analysis further suggesting induction of apoptosis. Pro-apoptotic effects were confirmed, as the extract enabled the activation of the effector caspase-3, broadening the knowledge on the anticancer mechanisms elicited by the fruits of X. aethiopica. Phenolic constituents might contribute to the cytotoxic effects, particularly via caspase-3 activation. Considering that X. aethiopica fruit is very often referred as an anticancer ingredient in Africa, but mainly the potent cytotoxicity herein recorded, our results call for additional research aiming to identify non-phenolic constituents contributing to the effects and also to further detail the anticancer mechanisms.

Comparative Study of Metabolomic Profile and Antioxidant Content of Adult and In Vitro Leaves of Aristotelia chilensis.

This work aimed to identify the bioactive compounds present in adult maqui (Aristotelia chilensis) leaves from different stages of development and seasons of the year and compare them with leaves obtained from maqui plants grown in vitro. The qualitative and quantitative analysis of maqui leaf extracts by HPLC-DAD-ESI-MSn showed the presence of different polyphenolic compounds classified into galloyl and caffeoyl quinic acids, ellagitannins and ellagic acid- and flavonoid-derivatives. In general, the total phenolic content of the in vitro samples was higher than that of ex vitro samples, whereas the total flavonoid content was higher in winter basal leaves. Additionally, the analysis by HPLC-MS showed that the extract from spring basal leaves was enriched in quercetin, catechin, kaempferol and 3-caffeoyl quinic acids, while in the in vitro leaves extract, quercetin was not present. As regards lipophilic compounds identified by GC/MS, the samples of in vitro leaves showed a high presence of α-tocopherol and ß-sitosterol. In contrast, the samples of adult leaves presented a hight level of linolenic and linoleic acids. These results suggest that maqui leaves could be an excellent source of antioxidants and lipophilic compounds for many industries, such as the nutraceutical and pharmaceutical industries.

Predicting the rising incidence and mortality of endometrial cancers among women aged 65-74 years in Catalonia.

Endometrial cancer is currently one of the most common gynecological cancers. Reported incidence rates vary in Spain depending on the region. We estimated what the incidence and mortality of endometrial cancers in Catalonia will be by 2030 and compared the predictions with data from 2010. Bayesian autoregressive age-period-cohort models were employed to predict incidence and mortality rates for 2015-2030. The incidence of endometrial cancer for women younger than 65 years was predicted to be lower in 2030 than in 2010, whereas it was predicted to be higher for women aged 65-74 years. Moreover, mortality rates for women aged ≥65 in 2030 are likely to exceed the rates in 2010. Five-year relative survival for all ages was slightly higher in the period 2005-2009 (79.3 %, 95 %CI: 75.8 %-82.9 %) compared with those in 1995-1999 (76.0 %, 95 %CI: 72.1 %-80.2 %). This plausible new scenario might be useful to plan new clinical and preventive strategies in the near future.

Characteristics of Adrenocortical Carcinoma Associated With Lynch Syndrome.

CONTEXT: Lynch syndrome (LS) is the most common inherited colorectal and endometrial cancer syndrome, caused by germline mutations in DNA mismatch repair (MMR) genes. It is also characterized by an increased risk of other tumors with lower prevalence, such as adrenal cortical carcinoma (ACC), an endocrine tumor with an incidence of <2 cases/million individuals/year. Most ACC developed during childhood are associated with hereditary syndromes. In adults, this association is not as well established as in children. Previous studies showed a 3.2% prevalence of LS among patients with ACC. EVIDENCE ACQUISITION: The objective of this study is to determine the prevalence of ACC in a Spanish LS cohort and their molecular and histological characteristics. This retrospective study includes 634 patients from 220 LS families registered between 1999 and 2018. EVIDENCE SYNTHESIS: During the follow-up period, 3 patients were diagnosed with ACC (0.47%); all were carriers of a MSH2 germline mutation. The 3 ACC patients presented loss of expression of MSH2 and MSH6 proteins. One tumor analysis showed loss of heterozygosity of the MSH2 wildtype allele. Our findings support previous data that considered ACC as a LS spectrum tumor. CONCLUSION: MMR protein immunohistochemistry screening could be an efficient strategy to detect LS in patients with ACC.