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3.
Radiología (Madr., Ed. impr.) ; 66(1): 57-69, Ene-Feb, 2024. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-229646

RESUMO

Los tumores cartilaginosos son un grupo amplio y heterogéneo de neoplasias caracterizadas por la presencia de una matriz condroide que presenta crecimiento lobular y patrones de calcificación en arcos y anillos o en palomitas de maíz. En RM destaca su hiperintensidad en las secuencias potenciadas en T2, y en las imágenes poscontraste, un relace lobulado o septal. En la clasificación de 2020 de la OMS, los tumores de estirpe condral se clasifican en benignos, intermedios o malignos. A pesar de los avances tecnológicos, siguen suponiendo un reto tanto para el radiólogo como para el patólogo, siendo la principal dificultad la diferenciación entre los tumores benignos y malignos, razón por la que requieren un abordaje multidisciplinar. Este trabajo recoge los principales cambios introducidos en la actualización de 2020, describe las características de imagen de los principales tumores cartilaginosos y proporciona las claves radiológicas para diferenciar entre tumores benignos y malignos.(AU)


Cartilaginous tumours are a large and heterogeneous group of neoplasms characterised by the presence of a chondroid matrix, with lobular growth and arcuate, ring-like or popcorn-like calcification patterns. MRI shows hyperintensity in T2-weighted sequences and a lobulated or septal relief in postcontrast images. In the WHO 2020 classification, chondral tumours are classified as benign, intermediate or malignant. Despite technological advances, they continue to pose a challenge for both the radiologist and the pathologist, being the main difficulty the differentiation between benign and malignant tumours, which is why they require a multidisciplinary approach. This paper describes the main changes introduced in the 2020 update, describes the imaging characteristics of the main cartilaginous tumours and provides the radiological keys to differentiate between benign and malignant tumours.(AU)


Assuntos
Humanos , Masculino , Feminino , Neoplasias/classificação , Organização Mundial da Saúde , Osteocondroma/diagnóstico por imagem , Condroma/diagnóstico por imagem , Condrossarcoma/diagnóstico por imagem , Cartilagem
4.
Nature ; 623(7986): 432-441, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37914932

RESUMO

Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis1-4. Although the genetic contributions to oncogenic transitions have been investigated, epigenetic drivers remain less understood. Here we constructed a pan-cancer epigenetic and transcriptomic atlas using single-nucleus chromatin accessibility data (using single-nucleus assay for transposase-accessible chromatin) from 225 samples and matched single-cell or single-nucleus RNA-sequencing expression data from 206 samples. With over 1 million cells from each platform analysed through the enrichment of accessible chromatin regions, transcription factor motifs and regulons, we identified epigenetic drivers associated with cancer transitions. Some epigenetic drivers appeared in multiple cancers (for example, regulatory regions of ABCC1 and VEGFA; GATA6 and FOX-family motifs), whereas others were cancer specific (for example, regulatory regions of FGF19, ASAP2 and EN1, and the PBX3 motif). Among epigenetically altered pathways, TP53, hypoxia and TNF signalling were linked to cancer initiation, whereas oestrogen response, epithelial-mesenchymal transition and apical junction were tied to metastatic transition. Furthermore, we revealed a marked correlation between enhancer accessibility and gene expression and uncovered cooperation between epigenetic and genetic drivers. This atlas provides a foundation for further investigation of epigenetic dynamics in cancer transitions.


Assuntos
Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias , Humanos , Hipóxia Celular , Núcleo Celular , Cromatina/genética , Cromatina/metabolismo , Elementos Facilitadores Genéticos/genética , Epigênese Genética/genética , Transição Epitelial-Mesenquimal , Estrogênios/metabolismo , Perfilação da Expressão Gênica , Proteínas Ativadoras de GTPase/metabolismo , Metástase Neoplásica , Neoplasias/classificação , Neoplasias/genética , Neoplasias/patologia , Sequências Reguladoras de Ácido Nucleico/genética , Análise de Célula Única , Fatores de Transcrição/metabolismo
5.
Transpl Int ; 36: 11552, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37663524

RESUMO

Although the association between post-transplant malignancy (PTM) and immunosuppressive therapy after organ transplantation has been studied, an integrated review of PTM after lung transplantation is lacking. We investigated the incidence and types of de novo PTM and its impact on survival following double lung transplantation (DLT). The incidence and type of PTM as well as the annual and cumulative risks of each malignancy after DLT were analyzed. The overall survival (OS) of recipients with or without PTM was compared by the Kaplan-Meier survival method and landmark analysis. There were 5,629 cases (23.52%) with 27 types of PTMs and incidences and OS varied according to the types of PTMs. The recipients with PTM showed a significantly longer OS than those without PTM (p < 0.001). However, while the recipients with PTM showed significantly better OS at 3, and 5 years (p < 0.001, p = 0.007), it was worse at the 10-year landmark time (p = 0.013). And the single PTM group showed a worse OS rate than the multiple PTM group (p < 0.001). This comprehensive report on PTM following DLT can help understand the risks and timing of PTM to improve the implementation of screening and treatment.


Assuntos
Terapia de Imunossupressão , Transplante de Pulmão , Neoplasias , Incidência , Risco , Terapia de Imunossupressão/efeitos adversos , Neoplasias/classificação , Neoplasias/epidemiologia , Neoplasias/mortalidade , Humanos , Masculino , Adulto , Pessoa de Meia-Idade
6.
An. sist. sanit. Navar ; 46(2): [e1042], May-Agos. 2023. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-224228

RESUMO

Fundamento: Analizar la supervivencia de pacientes adultosdiagnosticados de cáncer en Navarra, describir su tendencia ycompararla con la supervivencia en España. Métodos: Los casos de personas adultas diagnosticadas decáncer en los periodos 1999-2007 y 2008-2016 fueron seleccionados del registro poblacional de cáncer de Navarra; su esta-do vital se había actualizado hasta 2020. La supervivencia observada, la supervivencia neta (SN) y la SN estandarizada poredad (SNe) a cinco años, junto con sus intervalos de confianzaal 95%, fueron estimados globalmente y para veintinueve grupos de cáncer. Resultados. Se analizaron 57.564 casos. La SNe de los hombresy mujeres diagnosticados en 2008-2016 fue 59,9% (59,1-60,8) y63,8% (62,8-64,7), respectivamente. En hombres varió desde13,4% (10,4-17,4) en cáncer de páncreas hasta 94,0% (88,1-100) en el de tiroides, y en mujeres desde 11,9% (7,2-19,7) enel cáncer de hígado hasta 95,6% (92,6-98,6) en el de tiroides. Encomparación con los casos diagnosticados en 1999-2007, la SNeaumentó en diez grupos de cáncer, resultando un incrementoglobal de 5,1 (4,1-6,0) puntos porcentuales. La SNe en Navarrafue 2,7 (1,9-3,4) puntos porcentuales mayor que la descrita enEspaña en 2008-2013. Conclusiones: En Navarra la supervivencia de pacientes diagnosticados de cáncer en el periodo 2008-2016 mejoró significativamente respecto al periodo 1999-2007. Esta mejora obedece probablemente a múltiples factores, incluyendo diagnósticos mástempranos, opciones terapéuticas más efectivas y mejora delproceso asistencial. La supervivencia global fue mayor en las mujeres que en los hombres. Además, los resultados sugieren unasupervivencia más alta en Navarra en comparación con España.(AU)


Background: To analyze the survival of adult cancer patients inNavarre, describe its trend, and compare the data for this Spanish Autonomous Community against that reported for Spain. Methods: Records of adult cancer patients were retrieved fromthe Navarre’s population-based cancer registry for two periods(1999-2007 and 2008-2016). The vital status had been updated to2020. Observed survival, net survival and age-standardized netsurvival at five years with 95% confidence intervals were estimated overall and for twenty-nine cancer groups. Results: We analyzed 57,564 cases. Age-standardized net survival was 59.9% (59.1-60.8) and 63.8% (62.8-64.7) for males and females diagnosed with cancer during the 2008-2016 period,respectively. Age-standardized net survival ranged from 13.4%(10.4-17.4) for pancreatic cancer to 94.0% (88.1-100) for thyroidcancer in male patients, and from 11.9% (7.2-19.7) for livercancer to 95.6% (92.6-98.6-%) for thyroid cancer in female patients. Compared with cases diagnosed in the 1999-2007 period,age-standardized net survival increased in 10 cancer groups, resulting in an overall increase of 5.1 (4.1-6.0) percentage points.The age-standardized net survival in Navarre was 2.7 (1.9-3.4)percentage points higher than that described for Spain for the2008-2013 period. Conclusions: In Navarre, the survival of cancer patients diagnosed during the 2008-2016 period improved significantlyin comparison to the 1999-2007 period. Different factors mayexplain this improvement, including earlier diagnoses, moreeffective treatment options, and better healthcare processes.Overall, survival was higher in women than in men. Our resultssuggest a higher survival rate in Navarre than in Spain.(AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Neoplasias , Sobrevivência , Neoplasias/classificação , Espanha , Saúde Pública
8.
Nature ; 618(7965): 598-606, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37258682

RESUMO

Each tumour contains diverse cellular states that underlie intratumour heterogeneity (ITH), a central challenge of cancer therapeutics1. Dozens of recent studies have begun to describe ITH by single-cell RNA sequencing, but each study typically profiled only a small number of tumours and provided a narrow view of transcriptional ITH2. Here we curate, annotate and integrate the data from 77 different studies to reveal the patterns of transcriptional ITH across 1,163 tumour samples covering 24 tumour types. Among the malignant cells, we identify 41 consensus meta-programs, each consisting of dozens of genes that are coordinately upregulated in subpopulations of cells within many tumours. The meta-programs cover diverse cellular processes including both generic (for example, cell cycle and stress) and lineage-specific patterns that we map into 11 hallmarks of transcriptional ITH. Most meta-programs of carcinoma cells are similar to those identified in non-malignant epithelial cells, suggesting that a large fraction of malignant ITH programs are variable even before oncogenesis, reflecting the biology of their cell of origin. We further extended the meta-program analysis to six common non-malignant cell types and utilize these to map cell-cell interactions within the tumour microenvironment. In summary, we have assembled a comprehensive pan-cancer single-cell RNA-sequencing dataset, which is available through the Curated Cancer Cell Atlas website, and leveraged this dataset to carry out a systematic characterization of transcriptional ITH.


Assuntos
Regulação Neoplásica da Expressão Gênica , Heterogeneidade Genética , Neoplasias , Análise da Expressão Gênica de Célula Única , Humanos , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Neoplasias/classificação , Neoplasias/genética , Neoplasias/patologia , Microambiente Tumoral
9.
BMC Bioinformatics ; 24(1): 139, 2023 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37031189

RESUMO

BACKGROUND: Microarray data have been widely utilized for cancer classification. The main characteristic of microarray data is "large p and small n" in that data contain a small number of subjects but a large number of genes. It may affect the validity of the classification. Thus, there is a pressing demand of techniques able to select genes relevant to cancer classification. RESULTS: This study proposed a novel feature (gene) selection method, Iso-GA, for cancer classification. Iso-GA hybrids the manifold learning algorithm, Isomap, in the genetic algorithm (GA) to account for the latent nonlinear structure of the gene expression in the microarray data. The Davies-Bouldin index is adopted to evaluate the candidate solutions in Isomap and to avoid the classifier dependency problem. Additionally, a probability-based framework is introduced to reduce the possibility of genes being randomly selected by GA. The performance of Iso-GA was evaluated on eight benchmark microarray datasets of cancers. Iso-GA outperformed other benchmarking gene selection methods, leading to good classification accuracy with fewer critical genes selected. CONCLUSIONS: The proposed Iso-GA method can effectively select fewer but critical genes from microarray data to achieve competitive classification performance.


Assuntos
Algoritmos , Análise em Microsséries , Neoplasias , Humanos , Perfilação da Expressão Gênica/métodos , Técnicas Genéticas , Análise em Microsséries/métodos , Neoplasias/classificação , Neoplasias/genética , Probabilidade
10.
IEEE Trans Pattern Anal Mach Intell ; 45(9): 11008-11023, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37097802

RESUMO

Histopathological Whole Slide Images (WSIs) play a crucial role in cancer diagnosis. It is of significant importance for pathologists to search for images sharing similar content with the query WSI, especially in the case-based diagnosis. While slide-level retrieval could be more intuitive and practical in clinical applications, most methods are designed for patch-level retrieval. A few recently unsupervised slide-level methods only focus on integrating patch features directly, without perceiving slide-level information, and thus severely limits the performance of WSI retrieval. To tackle the issue, we propose a High-Order Correlation-Guided Self-Supervised Hashing-Encoding Retrieval (HSHR) method. Specifically, we train an attention-based hash encoder with slide-level representation in a self-supervised manner, enabling it to generate more representative slide-level hash codes of cluster centers and assign weights for each. These optimized and weighted codes are leveraged to establish a similarity-based hypergraph, in which a hypergraph-guided retrieval module is adopted to explore high-order correlations in the multi-pairwise manifold to conduct WSI retrieval. Extensive experiments on multiple TCGA datasets with over 24,000 WSIs spanning 30 cancer subtypes demonstrate that HSHR achieves state-of-the-art performance compared with other unsupervised histology WSI retrieval methods.


Assuntos
Histologia , Reconhecimento Automatizado de Padrão , Aprendizado de Máquina Supervisionado , Algoritmos , Análise por Conglomerados , Conjuntos de Dados como Assunto , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias/classificação , Neoplasias/diagnóstico , Neoplasias/patologia , Patologia/métodos , Reconhecimento Automatizado de Padrão/métodos , Aprendizado de Máquina não Supervisionado , Humanos
11.
Nature ; 613(7942): 96-102, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36517591

RESUMO

Expansion of a single repetitive DNA sequence, termed a tandem repeat (TR), is known to cause more than 50 diseases1,2. However, repeat expansions are often not explored beyond neurological and neurodegenerative disorders. In some cancers, mutations accumulate in short tracts of TRs, a phenomenon termed microsatellite instability; however, larger repeat expansions have not been systematically analysed in cancer3-8. Here we identified TR expansions in 2,622 cancer genomes spanning 29 cancer types. In seven cancer types, we found 160 recurrent repeat expansions (rREs), most of which (155/160) were subtype specific. We found that rREs were non-uniformly distributed in the genome with enrichment near candidate cis-regulatory elements, suggesting a potential role in gene regulation. One rRE, a GAAA-repeat expansion, located near a regulatory element in the first intron of UGT2B7 was detected in 34% of renal cell carcinoma samples and was validated by long-read DNA sequencing. Moreover, in preliminary experiments, treating cells that harbour this rRE with a GAAA-targeting molecule led to a dose-dependent decrease in cell proliferation. Overall, our results suggest that rREs may be an important but unexplored source of genetic variation in human cancer, and we provide a comprehensive catalogue for further study.


Assuntos
Expansão das Repetições de DNA , Genoma Humano , Neoplasias , Humanos , Sequência de Bases , Expansão das Repetições de DNA/genética , Genoma Humano/genética , Neoplasias/classificação , Neoplasias/genética , Neoplasias/patologia , Análise de Sequência de DNA , Regulação da Expressão Gênica , Elementos Reguladores de Transcrição/genética , Íntrons/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Proliferação de Células/efeitos dos fármacos , Reprodutibilidade dos Testes
12.
Braz. J. Pharm. Sci. (Online) ; 59: e22102, 2023. graf
Artigo em Inglês | LILACS | ID: biblio-1439521

RESUMO

Abstract EphrinB2 plays a critical role in tumor growth. In this study, we studied the antitumor activity of imperatorin derivative IMP-1 in renal cell carcinoma (RCC) by regulating EphrinB2 pathway.. Results showed that IMP-1 inhibited the proliferation of 786-O cells in a dose- and time-dependent manner. More importantly, knockdown and transfection of EphrinB2 altered the inhibitory effect of IMP-1 on the activity of 786-O cells. IMP-1 arrested 786-O cell cycle at G0/G1 phase by decreasing the expression of cyclin D1 and cyclin E. Moreover, IMP-1 regulated Bcl-2 family proteins' expression, thus inducing apoptosis of 786-O cells. IMP-1 down-regulated the expression of EphrinB2, Syntenin1 and PICK1. Then, IMP-1 decreased the phosphorylation of Erk1/2 and AKT. In all, IMP-1 could regulate the EphrinB2 pathway in order to inhibit 786-O cell growth by arresting the cell cycle at G0/G1 phase and inducing cell apoptosis. Thus, IMP-1 may present as a potential strategy for RCC treatment.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias/classificação , Fase G1/genética , Ciclina D1/efeitos adversos , Ciclina E/efeitos adversos
13.
Goiânia; SES-GO; 18 ago. 2022. 1-10 p. ilus, graf, mapas, tab.
Não convencional em Português | LILACS, CONASS, Coleciona SUS, SES-GO | ID: biblio-1398826

RESUMO

O crescimento desordenado de células no organismo, que pode invadir tecidos adjacentes ou órgãos em outras regiões do corpo, é denominado câncer (WHO, 2022a). A nomenclatura da doença corresponde ao local de foco inicial, e assim, os cânceres de mama, próstata, pulmão, colorretal, colo uterino e estômago são os mais frequentes. Globalmente, uma em cada seis mortes são relacionadas à doença, que configura a segunda principal causa de morte. E os tipos de câncer que mais evoluem para óbito são pulmão, mama, colorretal, fígado, próstata e estômago (WHO, 2022b)


The disordered growth of cells in the body, which can invade adjacent tissues or organs in other regions of the body, is called cancer (WHO, 2022a). The disease nomenclature corresponds to the initial focus site, and thus, breast, prostate, lung, colorectal, uterine cervix and stomach cancers are the most frequent. Globally, one in every six deaths are related to the disease, which is the second leading cause of death. And the types of cancer that most evolve to death are lung, breast, colorectal, liver, prostate and stomach (WHO, 2022b)


Assuntos
Humanos , Masculino , Feminino , Criança , Idoso , Neoplasias/epidemiologia , Neoplasias/classificação , Neoplasias/mortalidade
14.
Psicooncología (Pozuelo de Alarcón) ; 19(1): 27-43, 28 mar. 2022. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-203936

RESUMO

Objetivo: la pandemia por el COVID-19 está generando un importante impacto emocional en la población general y, en especial, en los pacientes crónicos, como los oncológicos. Además, ha supuesto cambios en la atención sanitaria. El presente estudio pretende conocer este impacto, en la población oncológica y, desde su propia experiencia, explorar sus estrategias de afrontamiento así como conocer su opinión sobre la atención sanitaria recibida. Metodología:participaron 118 pacientes pertenecientes a 5 centros hospitalarios de la provincia de Barcelona. Los datos fueron recogidos a través del cuestionario HADS y de un cuestionario ad-hoc para valorar el malestar emocional, las estrategias de afrontamiento, la percepción de riesgo de contagio, el apoyo social y los cambios ocurridos en la atención sanitaria. Resultados: el 51,4% de los participantes puntuaron alto en la escala de ansiedad y un 36% en la de depresión. La preocupación (73,7%), el miedo (72,8%), la ansiedad (56,1%) y la tristeza (56,1%) fueron las emociones más frecuentemente expresadas. El 74,1% se sintieron muy satisfechos con la atención sanitaria recibida y el 94,6% refirieron haberse sentido acompañados por su equipo sanitario. Respecto a la valoración de la telemedicina, un 40,7% manifestaron no estar a favor de esta alternativa mientras que el 33,7% consideraron que era una buena opción.Conclusiones: los pacientes oncológicos consideran que la pandemia ha afectado negativamente a su estado emocional y su calidad de vida. Conocer la opinión que tienen los pacientes sobre la telemedicina nos puede ayudar a definir más adecuadamente el uso de este tipo de asistencia (AU)


Objective:Covid-19 pandemic has had a profound emotional impact in general population and, especially, in patients with chronic diseases, like cancer patients. Moreover, it has placed unparalelled demands on healthcare systems. The aim of the present study is to explore this impact on oncology patients from their own experience, assess their coping strategies and also know their opinion about the healthcare assistance received. Method: One hundred and eighteen oncology patients from 5 different hospitals around Barcelona participated in the study. Data was collected using both HADS and an ad-hoc questionnaire which evaluated emotional distress, coping strategies, risk-contagion perception, social support and assessment of changes in healthcare assistance. Results:A total of 51.4% of the subjects presented high rates of anxiety and 36% depression. Worry (73.7%), fear (72.8%), anxiety and sadness (56.1%) were the most frequent emotions expressed. Around 74.1% of the sample felt very satisfied with the healthcare services and 94.6% felt supported by their health team. A 40.7% of the patients disagreed with telemedicine assessment, while 33.7% had predominantly a positive perception. Conclusions:Oncology patients considered that COVID-19 pandemic has negatively affected their emotional status and quality of life. Getting to know patients’ opinions about telemedicine may aid in facilitating care and improving its design to provide better and more efficient care (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Pandemias , Infecções por Coronavirus/psicologia , Pneumonia Viral/psicologia , Neoplasias/psicologia , Telemedicina , Neoplasias/classificação , Adaptação Psicológica , Estudos Prospectivos , Estudos Transversais , Qualidade de Vida , Inquéritos e Questionários
15.
Clin Transl Med ; 12(2): e683, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35184406

RESUMO

BACKGROUND: Emerging studies have proved that colonic inflammation caused by refractory inflammatory bowel disease (IBD) can initiate the colitis-associated cancer (CAC), but the transition from inflammation to carcinoma is still largely unknown. METHODS: In this study, mouse colitis and CAC models were established, and the RNA-seq by circRNA microarray was employed to identify the differentially expressed circRNAs and mRNAs in different comparisons (DSS vs. NC and AOM/DSS vs. DSS). The bioinformatics analyses were used to search the common characteristics in mouse colitis and CAC. RESULTS: The K-means clustering algorithm packaged these differential expressed circRNAs into subgroup analysis, and the data strongly implied that mmu_circ_0001109 closely correlated to the pro-inflammatory signals, while mmu_circ_0001845 was significantly associated with the Wnt signalling pathway. Our subsequent data in vivo and in vitro confirmed that mmu_circ_0001109 could exacerbate the colitis by up-regulating the Jak-STAT3 and NF-kappa B signalling pathways, and mmu_circ_0001845 promoted the CAC transformation through the Wnt signalling pathway. By RNA blasting between mice and humans, the human RTEL1- and PRKAR2A-derived circRNAs, which might be considered as homeotic circRNAs of mmu_circ_0001109 and mmu_circ_0001845, respectively, were identified. The clinical data revealed that RTEL1-derived circRNAs had no clinical significance in human IBD and CAC. However, three PRKAR2A-derived circRNAs, which had the high RNA similarities to mmu_circ_0001845, were remarkably up-regulated in CAC tissue samples and promoted the transition from colitis to CAC. CONCLUSIONS: Our results suggested that these human PRKAR2A-derived circRNAs could be novel candidates for distinguishing CAC patients and predicted the prognosis of CAC.


Assuntos
Colite/complicações , Neoplasias Colorretais/classificação , Subunidade RIIalfa da Proteína Quinase Dependente de AMP Cíclico/efeitos adversos , Neoplasias/classificação , Animais , Colite/genética , Neoplasias Colorretais/etiologia , Subunidade RIIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Subunidade RIIalfa da Proteína Quinase Dependente de AMP Cíclico/metabolismo , Modelos Animais de Doenças , Camundongos , Neoplasias/etiologia , RNA Circular
16.
Nat Commun ; 13(1): 617, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35105875

RESUMO

As cancer is increasingly considered a metabolic disorder, it is postulated that serum metabolite profiling can be a viable approach for detecting the presence of cancer. By multiplexing mass spectrometry fingerprints from two independent nanostructured matrixes through machine learning for highly sensitive detection and high throughput analysis, we report a laser desorption/ionization (LDI) mass spectrometry-based liquid biopsy for pan-cancer screening and classification. The Multiplexed Nanomaterial-Assisted LDI for Cancer Identification (MNALCI) is applied in 1,183 individuals that include 233 healthy controls and 950 patients with liver, lung, pancreatic, colorectal, gastric, thyroid cancers from two independent cohorts. MNALCI demonstrates 93% sensitivity at 91% specificity for distinguishing cancers from healthy controls in the internal validation cohort, and 84% sensitivity at 84% specificity in the external validation cohort, with up to eight metabolite biomarkers identified. In addition, across those six different cancers, the overall accuracy for identifying the tumor tissue of origin is 92% in the internal validation cohort and 85% in the external validation cohort. The excellent accuracy and minimum sample consumption make the high throughput assay a promising solution for non-invasive cancer diagnosis.


Assuntos
Detecção Precoce de Câncer/métodos , Lasers , Nanoestruturas/química , Neoplasias/classificação , Neoplasias/diagnóstico , Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , China , Estudos de Coortes , Feminino , Humanos , Aprendizado de Máquina , Masculino , Sensibilidade e Especificidade
17.
Nat Commun ; 13(1): 208, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-35017538

RESUMO

Cancer is often called a disease of aging. There are numerous ways in which cancer epidemiology and behaviour change with the age of the patient. The molecular bases for these relationships remain largely underexplored. To characterise them, we analyse age-associations in the nuclear and mitochondrial somatic mutational landscape of 20,033 tumours across 35 tumour-types. Age influences both the number of mutations in a tumour (0.077 mutations per megabase per year) and their evolutionary timing. Specific mutational signatures are associated with age, reflecting differences in exogenous and endogenous oncogenic processes such as a greater influence of tobacco use in the tumours of younger patients, but higher activity of DNA damage repair signatures in those of older patients. We find that known cancer driver genes such as CDKN2A and CREBBP are mutated in age-associated frequencies, and these alter the transcriptome and predict for clinical outcomes. These effects are most striking in brain cancers where alterations like SUFU loss and ATRX mutation are age-dependent prognostic biomarkers. Using three cancer datasets, we show that age shapes the somatic mutational landscape of cancer, with clinical implications.


Assuntos
Envelhecimento/genética , Proteína de Ligação a CREB/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Reparo do DNA , DNA de Neoplasias/genética , Proteínas de Neoplasias/genética , Neoplasias/genética , Fatores Etários , Envelhecimento/metabolismo , Proteína de Ligação a CREB/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , DNA de Neoplasias/metabolismo , Conjuntos de Dados como Assunto , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Mitocôndrias/metabolismo , Taxa de Mutação , Proteínas de Neoplasias/metabolismo , Neoplasias/classificação , Neoplasias/metabolismo , Neoplasias/patologia , Proteínas Repressoras/deficiência , Proteínas Repressoras/genética , Fumar/genética , Fumar/metabolismo , Transcriptoma , Proteína Nuclear Ligada ao X/genética , Proteína Nuclear Ligada ao X/metabolismo
18.
Isr Med Assoc J ; 24(1): 33-41, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35077043

RESUMO

BACKGROUND: Potentially preventable readmissions of surgical oncology patients offer opportunities to improve quality of care. Identifying and subsequently addressing remediable causes of readmissions may improve patient-centered care. OBJECTIVES: To identify factors associated with potentially preventable readmissions after index cancer operation. METHODS: The New York State hospital discharge database was used to identify patients undergoing common cancer operations via principal diagnosis and procedure codes between the years 2010 and 2014. The 30-day readmissions were identified and risk factors for potentially preventable readmissions were analyzed using competing risk analysis. RESULTS: A total of 53,740 cancer surgeries performed for the following tumor types were analyzed: colorectal (CRC) (42%), kidney (22%), liver (2%), lung (25%), ovary (4%), pancreas (4%), and uterine (1%). The 30-day readmission rate was 11.97%, 47% of which were identified as potentially preventable. The most common cause of potentially preventable readmissions was sepsis (48%). Pancreatic cancer had the highest overall readmission rate (22%) and CRC had the highest percentage of potentially preventable readmissions (51%, hazard ratio [HR] 1.42, 95% confidence interval [95%CI] 1.28-1.61). Risk factors associated with preventable readmissions included discharge disposition to a skilled nursing facility (HR 2.22, 95%CI 1.99-2.48) and the need for home healthcare (HR 1.61, 95%CI 1.48-1.75). CONCLUSIONS: Almost half of the 30-day readmissions were potentially preventable and attributed to high rates of sepsis, surgical site infections, dehydration, and electrolyte disorders. These results can be further validated for identifying broad targets for improvement.


Assuntos
Assistência ao Convalescente , Desidratação , Neoplasias , Readmissão do Paciente/estatística & dados numéricos , Serviços Preventivos de Saúde , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Infecção da Ferida Cirúrgica , Desequilíbrio Hidroeletrolítico , Assistência ao Convalescente/métodos , Assistência ao Convalescente/normas , Assistência ao Convalescente/estatística & dados numéricos , Desidratação/epidemiologia , Desidratação/etiologia , Desidratação/prevenção & controle , Feminino , Serviços de Assistência Domiciliar/normas , Humanos , Masculino , Pessoa de Meia-Idade , Determinação de Necessidades de Cuidados de Saúde , Neoplasias/classificação , Neoplasias/epidemiologia , Neoplasias/cirurgia , New York/epidemiologia , Alta do Paciente/normas , Serviços Preventivos de Saúde/métodos , Serviços Preventivos de Saúde/normas , Melhoria de Qualidade , Medição de Risco , Sepse/epidemiologia , Sepse/etiologia , Sepse/fisiopatologia , Instituições de Cuidados Especializados de Enfermagem/normas , Procedimentos Cirúrgicos Operatórios/métodos , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Desequilíbrio Hidroeletrolítico/epidemiologia , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/prevenção & controle
20.
Indian J Pathol Microbiol ; 65(1): 93-99, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35074971

RESUMO

CONTEXT: Circulating free DNA (cfDNA) analysis has emerged as novel noninvasive diagnostic biomarker in several solid tumors. Raised levels have been reported in several malignancies and may correlate with clinicopathological and treatment response. The current study was designed to assess the diagnostics of cfDNA in different tumor types of malignancies correlating with tumor (T), nodes (N), and metastases (M) stage. DESIGN: Serum samples were collected from treatment naïve cases with histologically diagnosed tumors including 23 brain tumors, 48 breasts, 50 gallbladder carcinoma (GBC), 13 lungs, 68 oral squamous cell carcinoma (OSCC), and 25 normal controls. CfDNA was quantified with real-time polymerase chain reaction (PCR), Invasive ductal carcinoma (IDC) using beta-globin gene amplification. Cut off values for diagnostics were calculated using receiver operating curve analysis. RESULTS: Contrary to other cfDNA studies where it was postulated that cfDNA would not cross the blood-brain barrier and reach the systemic circulation, we found detectable cfDNA in glioma with median (Q1-Q3) of 349.22 ng/ml (19.87-1276.58). Median cfDNA concentration in breast, gallbladder, lung, oral and normal controls was 328.72 (128.38-624.44), 778.50 (589.88-1864.35), 348.73 (194.67-483.61), 386.27 (47.88-959.67), and 74.12 (49.66-120.00), respectively. Grades I and II glioma had significantly lower levels compared to Grades III and IV (P = 0.0001). Significant difference in median cfDNA values in IDC and GBC was observed with increasing tumor grades, stage, T stage, nodal stage and metastasis and with stage of OSCC cases. CONCLUSION: CfDNA levels showed good diagnostic discrimination in glioma, GBC, breast, lung carcinoma, and OSCC. Significant increase in titers was evident with increase in cancer stage from I to IV in breast, GBC and OSCC.


Assuntos
Ácidos Nucleicos Livres/sangue , Neoplasias/diagnóstico , Neoplasias/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Feminino , Neoplasias da Vesícula Biliar/sangue , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/sangue , Neoplasias/classificação , Adulto Jovem
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