Maslinic acid (MA) is a natural triterpene present in high concentrations in the waxy skin of olives. We have previously reported that MA induces apoptotic cell death via the mitochondrial apoptotic ...pathway in HT29 colon cancer cells. Here, we show that MA induces apoptosis in Caco-2 colon cancer cells via the extrinsic apoptotic pathway in a dose-dependent manner. MA triggered a series of effects associated with apoptosis, including the cleavage of caspases -8 and -3, and increased the levels of t-Bid within a few hours of its addition to the culture medium. MA had no effect on the expression of the Bax protein, release of cytochrome-c or on the mitochondrial membrane potential. This suggests that MA triggered the extrinsic apoptotic pathway in this cell type, as opposed to the intrinsic pathway found in the HT29 colon-cancer cell line. Our results suggest that the apoptotic mechanism induced in Caco-2 may be different from that found in HT29 colon-cancer cells, and that in Caco-2 cells MA seems to work independently of p53. Natural antitumoral agents capable of activating both the extrinsic and intrinsic apoptotic pathways could be of great use in treating colon-cancer of whatever origin.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to date, but there are familial cases without mutations in these known genes. We ...sequenced the exomes of three unrelated individuals with hereditary PCC (cases) and identified mutations in MAX, the MYC associated factor X gene. Absence of MAX protein in the tumors and loss of heterozygosity caused by uniparental disomy supported the involvement of MAX alterations in the disease. A follow-up study of a selected series of 59 cases with PCC identified five additional MAX mutations and suggested an association with malignant outcome and preferential paternal transmission of MAX mutations. The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The incorporation of high precision vehicle positioning systems has been demanded by the autonomous electric vehicle (AEV) industry. For this reason, research on visual odometry (VO) and Artificial ...Intelligence (AI) to reduce positioning errors automatically has become essential in this field. In this work, a new method to reduce the error in the absolute location of AEV using fuzzy logic (FL) is presented. The cooperative data fusion of GPS, odometer, and stereo camera signals is then performed to improve the estimation of AEV localization. Although the most important challenge of this work focuses on the reduction in the odometry error in the vehicle, the defiance of synchrony and the information fusion of sources of different nature is solved. This research is integrated by three phases: data acquisition, data fusion, and statistical evaluation. The first one is data acquisition by using an odometer, a GPS, and a ZED camera in AVE’s trajectories. The second one is the data analysis and fuzzy fusion design using the MatLab 2019® fuzzy logic toolbox. The last is the statistical evaluation of the positioning error of the different sensors. According to the obtained results, the proposed model with the lowest error is that which uses all sensors as input (stereo camera, odometer, and GPS). It can be highlighted that the best proposed model manages to reduce the positioning mean absolute error (MAE) up to 25% with respect to the state of the art.
Purpose
To identify predictors of palliation for head and neck cancer treated with the “Hypo Trial” hypofractionated radiation therapy regimen in a clinical setting.
Design/Method
We retrospectively ...assessed 106 consecutive patients with incurable cancer, treated between January 2008 and December 2018. Regimen used was 30‐36Gy in 5‐6 biweekly fractions of 6Gy.
Results
The prescription dose was 30Gy in 57 (53.8%) patients and 36Gy in 49 (46.2%) patients. 89.6% patients completed the prescribed treatment. With a median follow‐up of 6.92 months, 79.2% of the patients experienced clinical palliation. Palliation was correlated with the radiation therapy dose (P = 0.05). Median overall and progression‐free survival (OS, PFS) were 7 and 4.63 months, respectively. Achieving palliation was associated to OS (P = 0.01).
Conclusions
This short palliative hypofractionated scheme resulted in a high rate of palliation, with excellent compliance and acceptable toxicity. Our results show that radiation dose is a predictive factor for palliation.
Abstract Background There are no studies assessing the evolution and patterns of genetic studies performed at diagnosis in acute myeloid leukemia (AML) patients. Such studies could help to identify ...potential gaps in our present diagnostic practices, especially in the context of increasingly complex procedures and classifications. Methods The REALMOL study (NCT05541224) evaluated the evolution, patterns, and clinical impact of performing main genetic and molecular studies performed at diagnosis in 7285 adult AML patients included in the PETHEMA AML registry (NCT02607059) between 2000 and 2021. Results Screening rates increased for all tests across different time periods (2000–2007, 2008–2016, and 2017–2021) and was the most influential factor for NPM1 , FLT3‐ITD , and next‐generation sequencing (NGS) determinations: NPM1 testing increased from 28.9% to 72.8% and 95.2% ( p < .001), whereas FLT3‐ITD testing increased from 38.1% to 74.1% and 95.9% ( p < .0001). NGS testing was not performed between 2000–2007 and only reached 3.5% in 2008–2016, but significantly increased to 72% in 2017–2021 ( p < .001). Treatment decision was the most influential factor to perform karyotype (odds ratio OR, 6.057; 95% confidence interval CI, 4.702–7.802), and fluorescence in situ hybridation (OR, 2.273; 95% CI, 1.901–2.719) studies. Patients ≥70 years old or with an Eastern Cooperative Oncology Group ≥2 were less likely to undergo these diagnostic procedures. Performing genetic studies were associated with a favorable impact on overall survival, especially in patients who received intensive chemotherapy. Conclusions This unique study provides relevant information about the evolving landscape of genetic and molecular diagnosis for adult AML patients in real‐world setting, highlighting the increased complexity of genetic diagnosis over the past 2 decades.
A retrospective analysis of 7285 cases over 2 decades. This study explores the evolution of diagnostic practices in acute myeloid leukemia patients, highlighting factors influencing test implementation and their association with patient outcomes.
The role of decentralized assessment of measurable residual disease (MRD) for risk stratification in acute myeloid leukemia (AML) remains largely unknown, and so it does which methodological aspects ...are critical to empower the evaluation of MRD with prognostic significance, particularly if using multiparameter flow cytometry (MFC). We analyzed 1076 AML patients in first remission after induction chemotherapy, in whom MRD was evaluated by MFC in local laboratories of 60 Hospitals participating in the PETHEMA registry. We also conducted a survey on technical aspects of MRD testing to determine the impact of methodological heterogeneity in the prognostic value of MFC. Our results confirmed the recommended cutoff of 0.1% to discriminate patients with significantly different cumulative-incidence of relapse (-CIR- HR:0.71, P < 0.001) and overall survival (HR: 0.73, P = 0.001), but uncovered the limited prognostic value of MFC based MRD in multivariate and recursive partitioning models including other clinical, genetic and treatment related factors. Virtually all aspects related with methodological, interpretation, and reporting of MFC based MRD testing impacted in its ability to discriminate patients with different CIR. Thus, this study demonstrated that "real-world" assessment of MRD using MFC is prognostic in patients at first remission, and urges greater standardization for improved risk-stratification toward clinical decisions in AML.
Objectives
The objective of this study is to investigate a multicenter study to establish if differences exist in the levator ani muscle avulsion (LAM) rates between deliveries performed with ...Malmstrom's vacuum and the Kiwi vacuum.
Study design
A prospective, multicenter observational study with 199 primiparous subjects was performed. All patients had undergone vaginal delivery by vacuum (Malmstrom's or Kiwi). Avulsion was defined as an abnormal insertion of LAM in the lower pubic branch in the multiplanar mode, as identified in the three central sections by transperineal 3/4D echography 6 months after delivery. The area of the levator hiatus was measured in the plane of minimum dimensions at rest, during the Valsalva maneuver and during contraction.
Results
LAM avulsion occurred in 33.1% of cases in which Malmstrom's vacuum was used and in 29.4% of cases in which the Kiwi vacuum was used (the difference was not statistically significant), which resulted in a crude odds ratio (OR) of 0.977 (0.426, 2.241; P = .957) and an adjusted OR of 2.90 (0.691; 12.20; P = .146). Women in the Malmstrom's vacuum group had a larger LHA at rest 14.77 vs 12.64 cm2; P = .001) and at maximum contraction (13.41 vs 10.83 cm2; P < 0.001) in comparison with the Kiwi group, although the difference did not reach statistical significance under Valsalva maneuver (18.71 vs 17.21 cm2; P = .051).Differences between both groups were detected in the measurements of the hiatus area levator at rest (14.77 vs 12.64 cm2), during the Valsalva maneuver (18.71 vs 17.21 cm2) and during maximum contraction (13.41 vs 10.83 cm2).
Conclusions
In the present study, Malmstrom's vacuum was not associated with a higher risk of LAM in comparison with Kiwi's Omnicup.
Adherence to a healthy diet offers a valuable intervention to compete against the increasing cases of ocular diseases worldwide, such as dry eye disorders, myopia progression, cataracts, glaucoma, ...diabetic retinopathy, or age macular degeneration. Certain amounts of micronutrients must be daily provided for proper functioning of the visual system, such as vitamins, carotenoids, trace metals and omega-3 fatty acids. Among natural foods, the following have to be considered for boosting eye/vision health: fish, meat, eggs, nuts, legumes, citrus fruits, nuts, leafy green vegetables, orange-colored fruits/vegetables, olives-olive oil, and dairy products. Nutritional supplements have received much attention as potential tools for managing chronic-degenerative ocular diseases. A systematic search of PubMed, Web of Science, hand-searched publications and historical archives were performed by the professionals involved in this study, to include peer-reviewed articles in which natural food, nutrient content, and its potential relationship with ocular health. Five ophthalmologists and two researchers collected the characteristics, quality and suitability of the above studies. Finally, 177 publications from 1983 to 2021 were enclosed, mainly related to natural food, Mediterranean diet (MedDiet) and nutraceutic supplementation. For the first time, original studies with broccoli and tigernut (chufa de Valencia) regarding the ocular surface dysfunction, macular degeneration, diabetic retinopathy and glaucoma were enclosed. These can add value to the diet, counteract nutritional defects, and help in the early stages, as well as in the course of ophthalmic pathologies. The main purpose of this review, enclosed in the Special Issue “Health Benefits and Nutritional Quality of Fruits, Nuts and Vegetables,” is to identify directions for further research on the role of diet and nutrition in the eyes and vision, and the potential antioxidant, anti-inflammatory and neuroprotective effects of natural food (broccoli, saffron, tigernuts and walnuts), the Mediterranean Diet, and nutraceutic supplements that may supply a promising and highly affordable scenario for patients at risk of vision loss. This review work was designed and carried out by a multidisciplinary group involved in ophthalmology and ophthalmic research and especially in nutritional ophthalmology.
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