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INTRODUCTION: Neoadjuvant cisplatinbased combination chemotherapy (NAC) followed by radical cystectomy is the standard of care for cisplatin-fit patients harboring muscle-invasive bladder cancer (MIBC). Prediction of response to NAC is essential for clinical decision-making regarding alternatives in case of non-response and bladder-sparing in case of complete response. This research aimed to assess the performance of machine learning in predicting therapeutic response following NAC treatment in patients with MIBC. METHODS: A systematic review adhering to the PRISMA guidelines was conducted until July 2023. The study integrated articles relating to artificial intelligence and NAC response in MIBC from various databases. The quality of articles was evaluated using the Quality Assessment Tool for Diagnostic Accuracy Studies 2 (QUADAS-2). A meta-analysis was subsequently performed on selected studies to determine the sensitivity and specificity of machine learning algorithms in predicting NAC response. RESULTS: Of 655 articles identified, 12 studies comprising 1523 patients were included, and four studies were eligible for meta-analysis. The sensitivity and specificity of the studies were 0.62 (95% confidence interval [CI] 0.50-0.72) and 0.82 (95% CI 0.72-0.89), respectively, with a heterogeneity score (I2) of 38.5%. The machine learning algorithms used computed tomography, genetic, and anatomopathological data as input and exhibited promising potential for predicting NAC response. CONCLUSIONS: Machine-learning algorithms, especially those using computed tomography, genetic, and pathologic data, demonstrate significant potential for predicting NAC response in MIBC. Standardization of methodologic data analysis and response criteria are needed as validation studies.
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PURPOSE: To evaluate the impact of the COVID-19 pandemic on the care of patients with bladder cancer in a tertiary oncology center. MATERIALS AND METHOD: We performed a retrospective analysis of patients admitted to a tertiary cancer center for the treatment of bladder cancer between 2019 and 2022. Surgical volumes, patient demographics, clinical characteristics, and postoperative outcomes were compared across these years. RESULTS: A total of 463 patients with bladder cancer were admitted in the period, and 78 patients underwent radical cystectomy . The distribution of TMN stages between admitted patients remained consistent across the years, with no statistically significant differences. Patients who underwent RC in 2020 presented more advanced disease at surgery (pT3/pT4 stage) (P = .045; 95% CI, 0.18-0.55) and had a longer hospital stay compared to other years (P = .024; 95% CI, 10.26-41.27). CONCLUSIONS: The COVID-19 pandemic posed significant challenges for the treatment of patients with bladder cancer. These results highlight the need to adapt health systems to unforeseen challenges, emphasizing the clinical impact on patients with advanced stages of the disease and the repercussions on their overall survival.
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Adenocarcinoma , Hidronefrosis , Centros de Atención Terciaria , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Hidronefrosis/etiología , Masculino , Femenino , Anciano , Pronóstico , Adenocarcinoma/patología , Persona de Mediana Edad , Estudios Retrospectivos , Anciano de 80 o más Años , AdultoRESUMEN
BACKGROUND: High-dose chemotherapy followed by stem cell transplant (HDCT) is potentially curative for patients with refractory germ cell tumors (rGCT). There is scarce real-world data supporting its implementation in low- and middle-income countries. We described the experience of our tertiary cancer center in Sao Paulo, Brazil. METHODS: We identified male patients ≥18 years-old with rGCT referred to HDCT after board discussion. Clinical data, including delays in HDCT protocol, were extracted from medical records, and survival outcomes were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazard were used to determine effects on overall survival (OS). RESULTS: From January 2013 to January 2023, 34 patients were referred and considered eligible to receive 2 cycles of HDCT. Most patients had primary testicular tumors (82%), nonseminomatous histology (88%), and poor International Germ Cell Collaborative Group (IGCCCG) (79%). Twenty-three patients received HDCT (1 cycle, n = 8; 2 cycles, n = 15). Main reasons for not receiving any HDCT were death due to progressive disease (n = 1), performance deterioration (n = 7), and failure of stem cell mobilization (n = 3). OS at 2 years was 36.7% for the eligible population, 56.1% for patients who underwent at least 1 HDCT, and 77.1% for those who had ≥2 cycles. The 2-year OS rate for patients not given HDCT was 0%. All patients had delays in protocol, and poor-risk patients had longer intervals from referral to protocol initiation (0.7 vs. 1.8 month, P < .01). CONCLUSION: Outcomes of patients who received ≥1 HDCT were encouraging; however, only 15 from 34 eligible patients were able to receive the planned 2 cycles of HDCT. Further strategies to minimize treatment delays in low- and middle-income countries are needed.
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Neoplasias de Células Germinales y Embrionarias , Centros de Atención Terciaria , Neoplasias Testiculares , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/terapia , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/patología , Brasil , Adulto , Centros de Atención Terciaria/estadística & datos numéricos , Neoplasias Testiculares/terapia , Neoplasias Testiculares/patología , Neoplasias Testiculares/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto Joven , Trasplante Autólogo , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Trasplante de Células Madre Hematopoyéticas/métodos , Terapia Combinada , AdolescenteRESUMEN
OBJECTIVE: To provide an updated view on the role of cell-free DNA as a predictor of pathological response to neoadjuvant therapy in patients with muscle-invasive bladder cancer. METHODS: A systematic review was conducted from September 2023 to October 2023. Selected studies from the MEDLINE and clinical trial databases were critically analyzed regarding the clinical efficacy of cell-free DNA as a predictive instrument after neoadjuvant therapy in bladder cancer. The methodological quality assessment was based on the QUADAS-2 tool. RESULTS: In this systematic review, we analyzed 5 studies encompassing a cumulative patient cohort of 780 individuals diagnosed with muscle-invasive bladder cancer, with a median follow-up ranging from 6 to 23 months. Among these studies, 4 primarily focused on detecting and analyzing circulating tumor DNA in plasma, while 1 study uniquely utilized cell-free tumor DNA in urine samples. The diagnostic accuracy of cell-free DNA in plasma ranges from 79% to 100%, indicating a variable yet significant predictive capability. In contrast, the study utilizing urinary cell-free DNA demonstrated an accuracy of 81% in predicting treatment response post-neoadjuvant chemotherapy. CONCLUSION: Cell-free DNA is emerging as a valuable biomarker for predicting response to neoadjuvant chemotherapy in patients with muscle-invasive bladder tumors.
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Biomarcadores de Tumor , ADN Tumoral Circulante , Terapia Neoadyuvante , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/terapia , Neoplasias de la Vejiga Urinaria/sangre , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Humanos , Terapia Neoadyuvante/métodos , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Resultado del Tratamiento , PronósticoRESUMEN
Introduction: Surgical intervention is the treatment of choice in patients with urachal carcinoma. Due to complications and to reduce hospital stay from open surgery, minimally invasive approaches are desirable. Nowadays, robotic-assisted surgery has become increasingly popular, and robot-assisted cystectomy can be performed in patients with urachal carcinoma with low complication rates. Methods: We performed a systematic review to search for studies that evaluated patients who underwent robotic-assisted surgery for urachal carcinoma. The outcomes of interest were the type of cystectomy performed, whether there was umbilicus resection, total operative time, console time, intraoperative complications, estimated blood loss, postoperative complications, time of hospitalisation, positive surgical margins and the presence of documented tumour recurrence. Results: In this study, we evaluated three cohorts comprising a total of 21 patients. The median follow-up period ranged from 8 to 40 months. Medium age was between 51 and 54 years, with a majority (63.1%) being male. One patient (5.2%) underwent a radical cystectomy, and 19 patients (94.7%) underwent to partial cystectomy. Umbilical resections were performed in all cases, and pelvic lymphadenectomy in 14 cases (73.6%). Recurrence occurred in three patients at a median of 17 months postoperation, two cases in the trocar insertion site. Additionally, there was one death, which was attributed to postoperative cardiovascular complications. Conclusion: Robotic-assisted partial cystectomy has a low incidence of adverse outcomes in patients with urachal carcinoma. Controlled studies, ideally randomised, are warranted to establish the comparative efficacy and safety of the robotic-assisted cystectomy approach relative to open surgery.
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OBJECTIVE: To validate the Cancer of the Bladder Risk Assessment (COBRA) score in patients with urothelial variants. METHODS: Epidemiological, clinical, radiological, and anatomopathological data were collected from patients with urothelial carcinoma who underwent radical cystectomy at the Institute of Cancer of São Paulo between May 2008 and December 2022. Patients with the presence of at least 10% of any urothelial variants in the radical cystectomy specimens' anatomopathological exam were included in the study. The COBRA score and derivatives were applied and correlated with oncological outcomes. RESULTS: A total of 680 patients [482 men (70.9%) and 198 women (29.1%)]; 66 years (IQR 59-73) underwent radical cystectomy for bladder tumor, and of these patients, a total of 167 patients presented any type of urothelial variant. The median follow-up time was 28.77 months (IQR 12-85). The three most prevalent UV were squamous differentiation (50.8%), glandular differentiation (31.3%), and micropapillary differentiation (11.3%). The subtypes with the worst prognosis were sarcomatoid with a median survival of 8 months (HR 1.161; 95% CI 0.555-2.432) and plasmacytoid with 14 months (HR 1.466; 95% CI 0.528-4.070). The COBRA score for patients with micropapillary variants demonstrated good predictive accuracy for OS (log-rank P = 0.009; 95% IC 6.78-29.21) and CSS (log-rank P = 0.002; 95% IC 13.06-26.93). CONCLUSIONS: In our study, the COBRA score proved an effective risk stratification tool for urothelial histological variants, especially for the micropapillary urothelial variant. It may be helpful in the prognosis evaluation of UV patients after radical cystectomy.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Masculino , Humanos , Femenino , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/patología , Cistectomía , Estudios Retrospectivos , Brasil , Medición de RiesgoRESUMEN
Objective: We aim to create a new score to predict postoperative overall survival in patients with nonmetastatic T3aN0 renal cell carcinoma. Methods: We reviewed the clinical data of adult patients who underwent radical nephrectomy for renal cell carcinoma between December 2007 and January 2022 in a single tertiary oncological institution. Clinical characteristics, clinical-pathological staging and histopathological characteristics were analysed. Survival analyses were determined using the Kaplan-Meier curve. A nomogram was established using Cox proportional hazard regression to identify the prognostic factors affecting the overall survival. The area under the curve, calibration curves and decision curve analysis were used to evaluate prognostic efficacy. Results: We analyzed 362 patients classified as pT3aN0M0 stage with a median follow-up of 40 months. According to Cox univariate and multivariate analyses, weight loss greater than 5% in 6 months before surgery, stage V chronic kidney disease after radical nephrectomy, sarcomatoid pattern, and coagulative tumor necrosis were identified as predictors of overall survival. We developed a score and performed internal and external validation. The time-dependent receiver operating characteristic curve, area under the curve value and calibration curve analysis showed good prediction ability of the score. The nomogram can effectively predict and stratify overall survival after radical nephrectomy in patients with pT3aN0M0 renal cell carcinoma. Conclusion: Patients with pT3aN0MO renal cell carcinoma exhibited different characteristics, and those with unfavourable characteristics deserve greater attention during follow-up. This nomogram provides an accurate prediction of overall survival after radical nephrectomy.
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Previous studies show that COVID-19 survivors have elevated muscle sympathetic nerve activity (MSNA), endothelial dysfunction, and aortic stiffening. However, the neurovascular responses to mental stress and exercise are still unexplored. We hypothesized that COVID-19 survivors, compared with age- and body mass index (BMI)-matched control subjects, exhibit abnormal neurovascular responses to mental stress and physical exercise. Fifteen severe COVID-19 survivors (aged: 49 ± 2 yr, BMI: 30 ± 1 kg/m2) and 15 well-matched control subjects (aged: 46 ± 3 yr, BMI: 29 ± 1 kg/m2) were studied. MSNA (microneurography), forearm blood flow (FBF), and forearm vascular conductance (FVC, venous occlusion plethysmography), mean arterial pressure (MAP, Finometer), and heart rate (HR, ECG) were measured during a 3-min mental stress (Stroop Color-Word Test) and during a 3-min isometric handgrip exercise (30% of maximal voluntary contraction). During mental stress, MSNA (frequency and incidence) responses were higher in COVID-19 survivors than in controls (P < 0.001), and FBF and FVC responses were attenuated (P < 0.05). MAP was similar between the groups (P > 0.05). In contrast, the MSNA (frequency and incidence) and FBF and FVC responses to handgrip exercise were similar between the groups (P > 0.05). MAP was lower in COVID-19 survivors (P < 0.05). COVID-19 survivors exhibit an exaggerated MSNA and blunted vasodilatory response to mental challenge compared with healthy adults. However, the neurovascular response to handgrip exercise is preserved in COVID-19 survivors. Overall, the abnormal neurovascular control in response to mental stress suggests that COVID-19 survivors may have an increased risk to cardiovascular events during mental challenge.
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COVID-19 , Fuerza de la Mano , Adulto , Humanos , Persona de Mediana Edad , Presión Sanguínea/fisiología , Hemodinámica , Ejercicio Físico/fisiología , Frecuencia Cardíaca/fisiología , Sistema Nervioso Simpático , Antebrazo/irrigación sanguínea , Músculo Esquelético/inervaciónRESUMEN
Objectives: This study aimed to evaluate the functional results of the treatment protocol for the treatment of transolecranon fracture-dislocation, by surgical reduction and osteosynthesis with plate and screws, in patients attended at a referral hospital for orthopedic trauma, with a minimum follow-up period of six months. Methods: Twenty-five individuals treated surgically from January 2014 to November 2018 were selected for a primary observational longitudinal study using questionnaires to assess upper limb and elbow function (DASH and MEPS), quality of life (SF-12), pain (visual analog scale - VAS), and radiographic evaluation in anteroposterior and lateral views of the elbow. Results: Fifteen patients were male, and the mean age was 46.8 years. All participants had their fractures consolidated, with no radiolgraphic signs of implant failure, or degenerative arthritis. Mean range of motion was reduced relative to the contralateral limb: 102.6º for flexion-extension and 132.8º for pronation-supination. The mean MEPS and DASH scores were 89.6 and 16.5 respectively. There was no residual pain in 84% of the cases according to the VAS. Conclusion: The surgical treatment proposed for transolecranon fracture-dislocations showed satisfactory results according to MEPS, DASH scores and quality of life measures. Evidence Level IV; Retrospective observational study.
Objetivo: Avaliar os resultados funcionais do protocolo de tratamento da fratura-luxação transolecraniana, por redução cirúrgica e osteossíntese com placa e parafusos, nos pacientes atendidos em hospital de referência para trauma ortopédico, com seguimento mínimo de seis meses. Métodos: vinte e cinco indivíduos tratados cirurgicamente de janeiro de 2014 a novembro de 2018 foram selecionados para um estudo longitudinal observacional primário, utilizando questionários para avaliar a função do membro superior e cotovelo (DASH e MEPS), qualidade de vida (SF-12), dor (visual escala analógica - EVA), e avaliação radiográfica nas incidências anteroposterior e perfil do cotovelo. Resultados: Quinze pacientes eram do sexo masculino e a média de idade foi de 46,8 anos. Todos os participantes tiveram suas fraturas consolidadas, sem sinais radiográficos de falha do implante ou artrite degenerativa. A amplitude média do movimento foi reduzida em relação ao membro contralateral: 102,6º para flexo-extensão e 132,8º para pronossupinação. Os escores médios de MEPS e DASH foram 89,6 e 16,5, respectivamente. Não houve dor residual em 84% dos casos de acordo com a EAV. Conclusão: O tratamento cirúrgico proposto para a fratura-luxação transolecraniana apresentou resultados satisfatórios de acordo com MEPS, escores DASH e medidas de qualidade de vida. Nível de evidência IV; Estudo observacional retrospectivo.
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It is increasingly becoming clear that cancers are a symbiosis of diverse cell types and tumor clones. Combined single-cell RNA sequencing, flow cytometry, and immunohistochemistry studies of the innate immune compartment in the bone marrow of patients with acute myeloid leukemia (AML) reveal a shift toward a tumor-supportive M2-polarized macrophage landscape with an altered transcriptional program, with enhanced fatty acid oxidation and NAD+ generation. Functionally, these AML-associated macrophages display decreased phagocytic activity and intra-bone marrow coinjection of M2 macrophages together with leukemic blasts strongly enhances in vivo transformation potential. A 2-day in vitro exposure to M2 macrophages results in the accumulation of CALRlow leukemic blast cells, which are now protected against phagocytosis. Moreover, M2-exposed "trained" leukemic blasts display increased mitochondrial metabolism, in part mediated via mitochondrial transfer. Our study provides insight into the mechanisms by which the immune landscape contributes to aggressive leukemia development and provides alternatives for targeting strategies aimed at the tumor microenvironment.
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Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/patología , Macrófagos/patología , Fagocitosis , Inmunohistoquímica , Microambiente TumoralRESUMEN
The research on porous materials for the selective capture of fluorinated gases (F-gases) is key to reduce their emissions. Here, the adsorption of difluoromethane (R-32), pentafluoroethane (R-125), and 1,1,1,2-tetrafluoroethane (R-134a) is studied in four metal-organic frameworks (MOFs: Cu-benzene-1,3,5-tricarboxylate, zeolitic imidazolate framework-8, MOF-177, and MIL-53(Al)) and in one zeolite (ZSM-5) with the aim to develop technologies for the efficient capture and separation of high global warming potential blends containing these gases. Single-component sorption equilibria of the pure gases are measured at three temperatures (283.15, 303.15, and 323.15 K) by gravimetry and correlated using the Tóth and Virial adsorption models, and selectivities toward R-410A and R-407F are determined by ideal adsorption solution theory. While at lower pressures, R-125 and R-134a are preferentially adsorbed in all materials, at higher pressures there is no selectivity, or it is shifted toward the adsorption R-32. Furthermore, at high pressures, MOF-177 shows the highest adsorption capacity for the three F-gases. The results presented here show that the utilization of MOFs, as tailored made materials, is promising for the development of new approaches for the selective capture of F-gases and for the separation of blends of these gases, which are used in commercial refrigeration.
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Background: The data we present are part of the CUARENTAGRI project, which involves all archipelagos of the Macaronesia (Azores, Madeira, Canary Islands and Cabo Verde). The project aims to: i) identify and evaluate the risks associated with the introduction of new arthropod pests; ii) study the population dynamics of selected arthropod pest species currently responsible for the damage of key target crops and iii) develop monitoring systems, based on prediction and/or population dynamics of the crop pests, creating warnings and a phytosanitary prevention system. In this contribution, we compile data for three Azorean Islands (Terceira, São Jorge and São Miguel Islands), where pheromone-baited traps were placed in pastures, potato fields and several orchards' types (apples, banana, chestnuts, olives, orange and strawberry), during three consecutive years (2020, 2021 and 2022). New information: A total of 114,827 specimens of insects (Arthropoda, Insecta) were collected, belonging to four orders, six families and ten recorded pest species. A total of eight species are considered introduced (Cosmopolitessordidus (Germar, 1824), Drosophilasuzukii (Matsumura, 1931), Bactroceraoleae (Rossi, 1790), Ceratitiscapitata (Wiedemann, 1824), Phthorimaeaoperculella (Zeller, 1873), Cydiapomonella (Linnaeus, 1758), Cydiasplendana (Hübner, 1799) and Grapholitamolesta (Busck, 1916); n = 84,986 specimens) and two native non-endemic (Mythimnaunipuncta (Haworth, 1809) and Spodopteralittoralis (Boisduval, 1833); n = 17,465 specimens). This study intended to contribute to a better knowledge of the arthropods pests that can affect the Azorean crops and will serve as a baseline for future monitoring actions, pest risk assessments and prevention systems.
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The COVID-19 pandemic has led to face-to-face activities being developed in a virtual format that often offers a poor experience in areas such as education. Virtual Learning Environments have improved in recent years thanks to new technologies such as Virtual Reality or Chatbots. However, creating Virtual Learning Environments requires advanced programming knowledge, so this work is aimed to enable teachers to create these new environments easily. This work presents a set of extensions for App Inventor that facilitate the authoring of mobile learning apps that use Chatbots in a Virtual Reality environment, while simultaneously monitoring of student activity. This proposal is based on integrating block-based languages and Business Process Model and Notation diagrams. The developed extensions were successfully implemented in an educational app called Let's date!. A quantitative analysis of the use of these extensions in App Inventor was also carried out, resulting in a significant reduction in the number of blocks required. The proposed contribution has demonstrated its validity in creating virtual learning environments through visual programming and modelling, reducing development complexity.
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Cytotoxic agents synergize with immune checkpoint inhibitors and improve outcomes for patients with several cancer types. Nonetheless, a parallel increase in the incidence of dose-limiting side effects, such as peripheral neuropathy, is often observed. Here, we investigated the role of the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis in the modulation of paclitaxel-induced neuropathic pain. We found that human and mouse neural tissues, including the dorsal root ganglion (DRG), expressed basal levels of PD-1 and PD-L1. During the development of paclitaxel-induced neuropathy, an increase in PD-L1 expression was observed in macrophages from the DRG. This effect depended on Toll-like receptor 4 activation by paclitaxel. Furthermore, PD-L1 inhibited pain behavior triggered by paclitaxel or formalin in mice, suggesting that PD-1/PD-L1 signaling attenuates peripheral neuropathy development. Consistent with this, we observed that the combined use of anti-PD-L1 plus paclitaxel increased mechanical allodynia and chronic neuropathy development induced by single agents. This effect was associated with higher expression of inflammatory markers (Tnf, Il6, and Cx3cr1) in peripheral nervous tissue. Together, these results suggest that PD-1/PD-L1 inhibitors enhance paclitaxel-induced neuropathic pain by suppressing PD-1/PD-L1 antinociceptive signaling.
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Antineoplásicos Fitogénicos , Neuralgia , Ratas , Humanos , Ratones , Animales , Receptor de Muerte Celular Programada 1 , Antineoplásicos Fitogénicos/efectos adversos , Ratas Sprague-Dawley , Neuralgia/inducido químicamente , Neuralgia/metabolismo , Paclitaxel , Analgésicos/efectos adversosRESUMEN
Recent advances in genomics during the 1990s have made it possible to study and identify genetic and epigenetic responses of cells and tissues to various drugs and environmental factors. This has accelerated the number of targets available to treat a range of diseases from cancer to wound healing disorders. Equally interesting is the understanding of how bio- and nanomaterials alter gene expression through epigenetic mechanisms, and whether they have the potential to elicit a positive therapeutic response without requiring additional biomolecule delivery. In fact, from a cell's perspective, a biomaterial is nothing more than an environmental factor, and so it has the power to epigenetically modulate gene expression of cells in contact with it. Understanding these epigenetic interactions between biomaterials and cells will open new avenues in the development of technologies that can not only provide biological signals (i.e. drugs, growth factors) necessary for therapy and regeneration, but also intimately interact with cells to promote the expression of genes of interest. This review article aims to summarise the current state-of-the-art and progress on the development of bio- and nanomaterials to modulate the epigenome.
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Nanoestructuras , Neoplasias , Materiales Biocompatibles/farmacología , Epigénesis Genética/genética , Epigenoma , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genéticaRESUMEN
Objectives: To evaluate how telomere length behaves in adamantinomtous craniopharyngioma (aCP) and if it contributes to the pathogenesis of aCPs with and without CTNNB1 mutations. Design: Retrospective cross-sectional study enrolling 42 aCP patients from 2 tertiary institutions. Methods: Clinicopathological features were retrieved from the patient's charts. Fresh frozen tumors were used for RNA and DNA analyses. Telomere length was evaluated by qPCR (T/S ratio). Somatic mutations in TERT promoter (TERTp) and CTNNB1 were detected by Sanger and/or whole-exome sequencing. We performed RNA-Seq to identify differentially expressed genes in aCPs presenting with shorter or longer telomere lengths. Results: Mutations in CTNNB1 were detected in 29 (69%) tumors. There was higher frequency of CTNNB1 mutations in aCPs from patients diagnosed under the age of 15 years (85% vs 15%; P = 0.04) and a trend to recurrent disease (76% vs 24%; P = 0.1). No mutation was detected in the TERTp region. The telomeres were shorter in CTNNB1-mutated aCPs (0.441, IQR: 0.297-0.597vs 0.607, IQR: 0.445-0.778; P = 0.04), but it was neither associated with clinicopathological features nor with recurrence. RNAseq identified a total of 387 differentially expressed genes, generating two clusters, being one enriched for short telomeres and CTNNB1-mutated aCPs. Conclusions: CTNNB1: mutations are more frequent in children and adolescents and appear to associate with progressive disease. CTNNB1-mutated aCPs have shorter telomeres, demonstrating a relationship between the Wnt/ß-catenin pathway and telomere biology in the pathogenesis of aCPs.
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Craneofaringioma , Telómero , beta Catenina , Adolescente , Niño , Craneofaringioma/genética , Estudios Transversales , Humanos , Mutación , Estudios Retrospectivos , Telómero/ultraestructura , Vía de Señalización Wnt , beta Catenina/genéticaRESUMEN
Resumen OBJETIVO: Comparar el índice neutrófilo-linfocito, la relación plaquetas-linfocito y la distribución de la anchura del eritrocito de mujeres con preeclampsia con o sin criterios de severidad y los de mujeres sin ésta. MATERIALES Y MÉTODOS: Estudio retrospectivo, de casos y controles, efectuado en mujeres con y sin preeclampsia atendidas entre enero y diciembre de 2019. RESULTADOS: Se estudiaron 70 mujeres con preeclampsia y 70 con embarazo sin esta complicación. El índice neutrófilo-linfocito fue significativamente mayor en las mujeres con preeclampsia (4.11 ± 2.76; IC95%: 3.47-4.75) que en las mujeres sin esta complicación (2.99 ± 1.6; IC95%: 2.62-3.36; p = 0.004), similar a la relación plaquetas-linfocitos (117.61 ± 47.53; IC95%:106.48-128.24 vs 97.64 ± 43.67; IC95%: 87.41-107.87; p = 0.006) y para la distribución de la anchura del eritrocito (14.46 ± 1.9; IC95%: 14.02-14.9 vs 13.56 ± 1.38; IC95%: 13-13.72; p = 0.0002). Ninguno de estos parámetros logró discriminar entre las pacientes con preeclampsia con o sin criterios de severidad. CONCLUSIÓN: Un índice neutrófilo-linfocito ≥ 5.1 y una relación plaquetas-linfocito ≥ 113.1 son capaces de discriminar de manera adecuada entre preeclampsia con o sin criterios de severidad.
Abstract OBJECTIVE: To compare the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and erythrocyte width distribution, of women with preeclampsia with or without severity criteria and those of women without. MATERIALS AND METHODS: Retrospective case-control study in 70 women with preeclampsia and 70 with normal pregnancy between January and December 2019. RESULTS: Seventy women with preeclampsia and 70 with pregnancy without this complication were studied. The neutrophil-lymphocyte ratio was significantly higher in women with preeclampsia (4.11 ± 2.76; 95%CI: 3.47-4.75), than in women with normal pregnancies (2.99 ± 1.6; 95%CI: 2.62-3.36; p = 0.004); which is similar for the platelet-lymphocyte ratio (117.61 ± 47.53, 95%CI: 106.48-128.24 vs 97.64 ± 43.67; 95%CI: 87.41-107.87; p = 0.006) and for the distribution of the width of the erythrocyte; (14.46 ± 1.9, CI95%: 14.02-14.9 vs 13.56 ± 1.38; CI95%: 13-13.72; p = 0.0002). None of these parameters was able to discriminate between patients with preeclampsia with or without severity criteria. A neutrophil-lymphocyte ratio ≥ 5.1 discriminates between women with a normal pregnancy and those with preeclampsia with or without severity criteria [area under the curve of 0.746, (95%CI: 0.664-0.827)], sensitivity 42%, specificity 91%, positive predictive value 82%, negative predictive value 60% and Odds Ratio 7.1 (95%CI: 2.7-18.6, p = 0.001). The platelet-lymphocyte ratio ≥ 113.4 can discriminate between women with a normal pregnancy and preeclampsia with or without severity criteria, with an area under the curve of 0.617 (95% CI 0.525-0.709). CONCLUSION: A neutrophil-lymphocyte ratio ≥ 5.1, and a platelet-lymphocyte ratio ≥ 113.1 are able to adequately discriminate between patients with normal pregnancy and those with preeclampsia with or without severity criteria.
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BACKGROUND: It is still controversial if activating mutations in the stimulatory G-protein α subunit (gsp mutation) are a biomarker of response to first generation somatostatin receptor ligands (fg-SRL) treatment in acromegaly. Thus, we aimed to evaluate whether gsp mutation predicts long-term response to fg-SRL treatment and to characterize the phenotype of patients harboring gsp mutations. METHODS: GNAS1 sequencing was performed by Sanger. SST2 and SST5 were analyzed by immunohistochemistry (IHC) and real-time RT-PCR. The cytokeratin granulation pattern was evaluated by IHC. Biochemical control was defined as GH < 1.0 ng/mL and normal age-adjusted IGF-I levels. RESULTS: gsp mutation was found in 54 out of 136 patients evaluated. Biochemical control with fg-SRL treatment was similar in gsp+ and gsp- patients (37% vs. 25%, p = 0.219). Tumors harboring gsp mutation were smaller (p = 0.035) and had a lower chance of invading cavernous sinuses (p = 0.001). SST5 protein (p = 0.047) and mRNA (p = 0.013) expression levels were higher in wild-type tumors. CONCLUSIONS: In this largest series available in the literature, we concluded that gsp is not a molecular biomarker of response to fg-SRL treatment in acromegaly. However, the importance of its negative association with cavernous sinus invasion and SST5 expression needs to be further investigated.