3,873 research outputs found

    Role of vitamins A, C, D, E in cancer prevention and therapy: therapeutic potentials and mechanisms of action

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    Cancer, a leading global cause of mortality, arises from intricate interactions between genetic and environmental factors, fueling uncontrolled cell growth. Amidst existing treatment limitations, vitamins have emerged as promising candidates for cancer prevention and treatment. This review focuses on Vitamins A, C, E, and D because of their protective activity against various types of cancer. They are essential as human metabolic coenzymes. Through a critical exploration of preclinical and clinical studies via PubMed and Google Scholar, the impact of these vitamins on cancer therapy was analyzed, unraveling their complicated mechanisms of action. Interestingly, vitamins impact immune function, antioxidant defense, inflammation, and epigenetic regulation, potentially enhancing outcomes by influencing cell behavior and countering stress and DNA damage. Encouraging clinical trial results have been observed; however, further well-controlled studies are imperative to validate their effectiveness, determine optimal dosages, and formulate comprehensive cancer prevention and treatment strategies. Personalized supplementation strategies, informed by medical expertise, are pivotal for optimal outcomes in both clinical and preclinical contexts. Nevertheless, conclusive evidence regarding the efficacy of vitamins in cancer prevention and treatment is still pending, urging further research and exploration in this compelling area of study

    PANCREATODUODENECTOMY FOR MALIGNANCY: FACTORS INFLUENCING SURGICAL AND ONCOLOGICAL OUTCOMES

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    Introduction: Fit patients with a resectable pancreatic head adenocarcinoma (PDAC), ampullary adenocarcinoma (AA) or distal cholangiocarcinoma (CC) may be offered pancreatoduodenectomy (PD) with curative-intent. However, perioperative morbidity and cancer recurrence rates are high. This thesis aimed to explore the factors influencing PD outcomes. A focus was placed on nutrition, postoperative complications, and recurrence in AA patients. It is hoped the findings will guide patient selection/consenting and have implications for patient management. Methods: A retrospective cohort study of patients who underwent PD for histologically-confirmed malignancy was carried out (2012-2015). Twenty-nine centres from eight countries were involved. Data on the following were collected: preoperative comorbidities and investigations, neoadjuvant treatment, operative details, postoperative complications, histology, adjuvant treatment, cancer recurrence, palliative treatment, and overall survival (OS). Results: In total, 1484 patients were included; 885 (59.6%), 394 (26.5%) and 205 (13.8%) had PDAC, AA and CC, respectively. Overall morbidity, major morbidity (Clavien-Dindo grade 11 ≥III) and 90-day mortality rates were 53.4%, 16.9% and 3.8%, respectively. A high body mass index (BMI), an American Society of Anesthesiologists (ASA) grade >II and a classic Whipple approach all correlated with morbidity. Additionally, ASA grade >II patients were at increased risk of major morbidity and a raised BMI correlated with a greater risk of pancreatic leak. Almost half of the cohort received nutritional support (NS). Of these, 55.6% received parenteral nutrition (PN). In total, 19.6% of the patients who had an uneventful postoperative recovery received PN. Among the PDAC cohort, commencing adjuvant chemotherapy (AC) correlated with improved OS, and those who experienced major morbidity commenced AC less frequently. Among the AA cohort, 176 patients (44.7%) developed recurrence and the median time-to-recurrence was 14 months. Local only, local and distant, and distant only recurrence affected 34, 41 and 94 patients, respectively (site unknown: 7). A higher number of resected nodes, histological T stage >II, lymphatic invasion, perineural invasion (PNI), peripancreatic fat invasion (PPFI) and ≥1 positive resection margin all correlated with AA recurrence. Further, ≥1 positive margin, PPFI and PNI were associated with reduced time-to-recurrence. Conclusions: A considerable number of the patients that had an uneventful recovery received PN. Patients with a high BMI or ASA grade had worse perioperative outcomes. Those who experienced major morbidity commenced AC less frequently. Numerous histopathological predictors of AA recurrence and reduced time-to-recurrence were identified

    It doesn't end with closure:Optimizing health care throughout life after esophageal atresia repair

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    3D Innovations in Personalized Surgery

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    Current practice involves the use of 3D surgical planning and patient-specific solutions in multiple surgical areas of expertise. Patient-specific solutions have been endorsed for several years in numerous publications due to their associated benefits around accuracy, safety, and predictability of surgical outcome. The basis of 3D surgical planning is the use of high-quality medical images (e.g., CT, MRI, or PET-scans). The translation from 3D digital planning toward surgical applications was developed hand in hand with a rise in 3D printing applications of multiple biocompatible materials. These technical aspects of medical care require engineers’ or technical physicians’ expertise for optimal safe and effective implementation in daily clinical routines.The aim and scope of this Special Issue is high-tech solutions in personalized surgery, based on 3D technology and, more specifically, bone-related surgery. Full-papers or highly innovative technical notes or (systematic) reviews that relate to innovative personalized surgery are invited. This can include optimization of imaging for 3D VSP, optimization of 3D VSP workflow and its translation toward the surgical procedure, or optimization of personalized implants or devices in relation to bone surgery

    Effects of municipal smoke-free ordinances on secondhand smoke exposure in the Republic of Korea

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    ObjectiveTo reduce premature deaths due to secondhand smoke (SHS) exposure among non-smokers, the Republic of Korea (ROK) adopted changes to the National Health Promotion Act, which allowed local governments to enact municipal ordinances to strengthen their authority to designate smoke-free areas and levy penalty fines. In this study, we examined national trends in SHS exposure after the introduction of these municipal ordinances at the city level in 2010.MethodsWe used interrupted time series analysis to assess whether the trends of SHS exposure in the workplace and at home, and the primary cigarette smoking rate changed following the policy adjustment in the national legislation in ROK. Population-standardized data for selected variables were retrieved from a nationally representative survey dataset and used to study the policy action’s effectiveness.ResultsFollowing the change in the legislation, SHS exposure in the workplace reversed course from an increasing (18% per year) trend prior to the introduction of these smoke-free ordinances to a decreasing (−10% per year) trend after adoption and enforcement of these laws (β2 = 0.18, p-value = 0.07; β3 = −0.10, p-value = 0.02). SHS exposure at home (β2 = 0.10, p-value = 0.09; β3 = −0.03, p-value = 0.14) and the primary cigarette smoking rate (β2 = 0.03, p-value = 0.10; β3 = 0.008, p-value = 0.15) showed no significant changes in the sampled period. Although analyses stratified by sex showed that the allowance of municipal ordinances resulted in reduced SHS exposure in the workplace for both males and females, they did not affect the primary cigarette smoking rate as much, especially among females.ConclusionStrengthening the role of local governments by giving them the authority to enact and enforce penalties on SHS exposure violation helped ROK to reduce SHS exposure in the workplace. However, smoking behaviors and related activities seemed to shift to less restrictive areas such as on the streets and in apartment hallways, negating some of the effects due to these ordinances. Future studies should investigate how smoke-free policies beyond public places can further reduce the SHS exposure in ROK

    Immune contexture monitoring in solid tumors focusing on Head and Neck Cancer

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    Forti evidenze dimostrano una stretta interazione tra il sistema immunitario e lo sviluppo biologico e la progressione clinica dei tumori solidi. L'effetto che il microambiente immunitario del tumore può avere sul comportamento clinico della malattia è indicato come "immunecontexture". Nonostante ciò, l'attuale gestione clinica dei pazienti affetti da cancro non tiene conto di alcuna caratteristica immunologica né per la stadiazione né per le scelte terapeutiche. Il tumore della testa e del collo (HNSCC) rappresenta il 7° tumore più comune al mondo ed è caratterizzato da una prognosi relativamente sfavorevole e dall'effetto negativo dei trattamenti sulla qualità della vita dei pazienti. Oltre alla chirurgia e alla radioterapia, sono disponibili pochi trattamenti sistemici, rappresentati principalmente dalla chemioterapia a base di platino-derivati o dal cetuximab. L'immunoterapia è una nuova strategia terapeutica ancora limitata al setting palliativo (malattia ricorrente non resecabile o metastatica). La ricerca di nuovi biomarcatori o possibili nuovi meccanismi target è molto rilevante quindi nel contesto clinico dell'HNSCC. In questa tesi ci si concentrerà sullo studio di tre possibili popolazioni immunitarie pro-tumorali studiate nell'HNSCC: i neutrofili tumore-associati (TAN), le cellule B intratumorali con fenotipo immunosoppressivo e i T-reg CD8+. Particolare attenzione è data all'applicazione di moderne tecniche biostatistiche e bioinformatiche per riassumere informazioni complesse derivate da variabili cliniche e immunologiche multiparametriche e per validare risultati derivati ​​in situ, attraverso dati di espressione genica derivati da dataset pubblici. Infine, la seconda parte della tesi prenderà in considerazione progetti di ricerca clinica rilevanti, volti a migliorare l'oncologia di precisione nell'HNSCC, sviluppando modelli predittivi di sopravvivenza, confrontando procedure oncologiche alternative, validando nuovi classificatori o testando l'uso di nuovi protocolli clinici come l'uso dell'immunonutrizione.Strong evidences demonstrate a close interplay between the immune system and the biological development and clinical progression of solid tumors. The effect that the tumor immune microenvironment can have on the clinical behavior of the disease is referred as the immuno contexture. Nevertheless, the current clinical management of patients affected by cancer does not take into account any immunological features either for the staging or for the treatment choices. Head and Neck Cancer (HNSCC) represents the 7th most common cancer worldwide and it is characterized by a relatively poor prognosis and detrimental effect of treatments on the quality of life of patients. Beyond surgery and radiotherapy, few systemic treatments are available, mainly represented by platinum-based chemotherapy or cetuximab. Immunotherapy is a new therapeutical strategy still limited to the palliative setting (recurrent not resectable or metastatic disease). The search for new biomarkers or possible new targetable mechanisms is meaningful especially in the clinical setting of HNSCC. In this thesis a focus will be given on the study of three possible pro-tumoral immune populations studied in HNSCC: the tumor associated neutrophils (TAN), intratumoral B-cells with a immunosuppressive phenotype and the CD8+ T-regs. Biostatistical and bioinformatical techniques are applied to summarize complex information derived from multiparametric clinical and immunological variables and to validate in-situ derived findings through gene expression data of public available datasets. Lastly, the second part of the thesis will take into account relevant clinical research projects, aimed at improving the precision oncology in HNSCC developing survival prediction models, comparing alternative oncological procedures, validating new classifiers or testing the use of novel clinical protocols as the use of immunnutrition

    Deep learning-based tool for radiomics analysis of cancer 3D multicellular spheroids

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    Cancer 3D multicellular spheroids are a fundamental in vitro tool for studying in vivo tumors. Volume is the main feature used for evaluating the drug and treatment effects, but several other features can be estimated even from a simple 2D image. For high-content screening analysis, the bottleneck is the segmentation stage, which is essential for detecting the spheroids in the images and then proceeding to the feature extraction stage for performing radiomic analysis. Thanks to new deep learning models, it is possible to optimize the process for adapting the analysis to big datasets. One of the most promising approaches is the use of convolutional neural networks (CNNs), which have shown remarkable results in various medical imaging applications. By training a CNN on a large dataset of annotated images, it can learn to recognize patterns and features that are relevant for segmenting spheroids in new images. This approach has several advantages, such as manual or semi-automatic segmentation, which are time-consuming and prone to inter-observer variability. Moreover, CNNs can be fine-tuned for specific tasks and can handle different types of data, such as multi-modal or multi-dimensional images. Starting from the first version of Analysis of SPheroids (AnaSP), an open-source software for estimating morphological features of spheroids, we implemented a new module for automatically segmenting brightfield images by exploiting CNNs. In this work, several deep learning segmentation models have been trained and compared using ground truth masks. Then, a module based on an 18-layer deep residual network (ResNet18) was integrated into AnaSP, releasing AnaSP 2.0, a version of the tool optimized for high-content screening analysis
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