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1.
Clin Chem ; 70(1): 81-89, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38175586

RESUMO

BACKGROUND: Metastasis is the leading cause of cancer-related deaths. Most studies have focused on the primary tumor or on overt metastatic lesions, leaving a significant knowledge gap concerning blood-borne cancer cell dissemination, a major step in the metastatic cascade. Circulating tumor cells (CTCs) in the blood of patients with solid cancer can now be enumerated and investigated at the molecular level, giving unexpected information on the biology of the metastatic cascade. CONTENT: Here, we reviewed recent advances in basic and translational/clinical research on CTCs as key elements in the metastatic cascade. SUMMARY: Findings from translational studies on CTCs have elucidated the complexity of the metastatic process. Fully understanding this process will open new potential avenues for cancer therapeutic and diagnostic strategies to propose precision medicine to all cancer patients.


Assuntos
Células Neoplásicas Circulantes , Humanos , Pesquisa Translacional Biomédica , Conhecimento , Medicina de Precisão
2.
Br J Cancer ; 130(1): 63-72, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37973956

RESUMO

BACKGROUND: Circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), and extracellular vesicles (EVs) are minimally invasive liquid biopsy biomarkers. This study investigated whether they predict prognosis, alone or in combination, in heterogenous unbiased non-small cell lung cancer (NSCLC) patients. METHODS: Plasma samples of 54 advanced NSCLC patients from a prospective clinical trial. CtDNA mutations were identified using the UltraSEEK™ Lung Panel (MassARRAY® technology). PD-L1 expression was assessed in small EVs (sEVs) using an enzyme-linked immunosorbent assay. RESULTS: At least one ctDNA mutation was detected in 37% of patients. Mutations were not correlated with overall survival (OS) (HR = 1.1, 95% CI = 0.55; 1.83, P = 0.980) and progression-free survival (PFS) (HR = 1.00, 95% CI = 0.57-1.76, P = 0.991). High PD-L1+ sEV concentration was correlated with OS (HR = 1.14, 95% CI = 1.03-1.26, P = 0.016), but not with PFS (HR = 1.08, 95% CI = 0.99-1.18, P = 0.095). The interaction analysis suggested that PD-L1+ sEV correlation with PFS changed in function of CTC presence/absence (P interaction = 0.036). The combination analysis highlighted worse prognosis for patients with CTCs and high PD-L1+ sEV concentration (HR = 7.65, 95% CI = 3.11-18.83, P < 0.001). The mutational statuses of ctDNA and tumour tissue were significantly correlated (P = 0.0001). CONCLUSION: CTCs and high PD-L1+ sEV concentration correlated with PFS and OS, but not ctDNA mutations. Their combined analysis may help to identify patients with worse OS. TRIAL REGISTRATION: NCT02866149, Registered 01 June 2015, https://clinicaltrials.gov/ct2/show/study/NCT02866149 .


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Vesículas Extracelulares , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Prognóstico , Neoplasias Pulmonares/patologia , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Estudos Prospectivos , Vesículas Extracelulares/metabolismo , Biópsia Líquida , Biomarcadores Tumorais/genética
3.
Cancer Med ; 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38132919

RESUMO

BACKGROUND: For several years, the AXL tyrosine kinase receptor, a member of the Tyro3-Axl-Mer (TAM) family, has been considered a new strategic target in oncology. AXL overexpression is common in solid tumors and is associated with poor prognosis. In this context, the detection of a subset of circulating tumor cells (CTCs) that express AXL (AXL+ CTCs) could be clinically relevant. METHODS: Immunostaining was performed to assess AXL expression in human breast cancer cell lines. The optimal conditions were established using flow cytometry. Spiking experiments were carried out to optimize the parameters of the CellSearch® system detection test. CTC enumeration and AXL expression were evaluated in patients with metastatic breast cancer (mBC) before treatment initiation. RESULTS: An innovative AXL+ CTC detection assay to be used with the CellSearch® system was developed. In a prospective longitudinal clinical trial, blood samples from 60 patients with untreated mBC were analyzed to detect AXL+ CTCs with this new assay. CTCs were detected in 35/60 patients (58.3%) and AXL+ CTCs were identified in 7 of these 35 patients (11.7% of all patients). CONCLUSION: This newly established AXL+ CTC assay is a promising tool that can be used for liquid biopsy in future clinical trials to stratify and monitor patients with cancer receiving anti-AXL therapies.

4.
Front Cell Dev Biol ; 11: 1209846, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601099

RESUMO

Background: Platelets are active players in hemostasis, coagulation and also tumorigenesis. The cross-talk between platelets and circulating tumor cells (CTCs) may have various pro-cancer effects, including promoting tumor growth, epithelial-mesenchymal transition (EMT), metastatic cell survival, adhesion, arrest and also pre-metastatic niche and metastasis formation. Interaction with CTCs might alter the platelet transcriptome. However, as CTCs are rare events, the cross-talk between CTCs and platelets is poorly understood. Here, we used our established colon CTC lines to investigate the colon CTC-platelet cross-talk in vitro and its impact on the behavior/phenotype of both cell types. Methods: We exposed platelets isolated from healthy donors to thrombin (positive control) or to conditioned medium from three CTC lines from one patient with colon cancer and then we monitored the morphological and protein expression changes by microscopy and flow cytometry. We then analyzed the transcriptome by RNA-sequencing of platelets indirectly (presence of a Transwell insert) co-cultured with the three CTC lines. We also quantified by reverse transcription-quantitative PCR the expression of genes related to EMT and cancer development in CTCs after direct co-culture (no Transwell insert) with platelets. Results: We observed morphological and transcriptomic changes in platelets upon exposure to CTC conditioned medium and indirect co-culture (secretome). Moreover, the expression levels of genes involved in EMT (p < 0.05) were decreased in CTCs co-cultured with platelets, but not of genes encoding mesenchymal markers (FN1 and SNAI2). The expression levels of genes involved in cancer invasiveness (MYC, VEGFB, IL33, PTGS2, and PTGER2) were increased. Conclusion: For the first time, we studied the CTC-platelet cross-talk using our unique colon CTC lines. Incubation with CTC conditioned medium led to platelet aggregation and activation, supporting the hypothesis that their interaction may contribute to preserve CTC integrity during their journey in the bloodstream. Moreover, co-culture with platelets influenced the expression of several genes involved in invasiveness and EMT maintenance in CTCs.

5.
Nucleic Acids Res ; 51(1): 1-16, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-35697349

RESUMO

Transcriptional reactivation of hTERT is the limiting step in tumorigenesis. While mutations in hTERT promoter present in 19% of cancers are recognized as key drivers of hTERT reactivation, mechanisms by which wildtype hTERT (WT-hTERT) promoter is reactivated, in majority of human cancers, remain unknown. Using primary colorectal cancers (CRC) we identified Tert INTeracting region 2 (T-INT2), the critical chromatin region essential for reactivating WT-hTERT promoter in CRCs. Elevated ß-catenin and JunD level in CRC facilitates chromatin interaction between hTERT promoter and T-INT2 that is necessary to turn on hTERTexpression. Pharmacological screens uncovered salinomycin, which inhibits JunD mediated hTERT-T-INT2 interaction that is required for the formation of a stable transcription complex on the hTERT promoter. Our results showed for the first time how known CRC alterations, such as APC, lead to WT-hTERT promoter reactivation during stepwise-tumorigenesis and provide a new perspective for developing cancer-specific drugs.


Healthy and cancer cells harbor the same DNA sequence, but reactivation of the Human Telomerase Reverse Transcriptase (hTERT) gene is observed only in cancer cells. How does that happen was not known for over three decades of research? This study identifies a specific DNA structure that forms only in cancer cells and brings the necessary molecular machinery into the correct position to activate the hTERT gene. The detailed mechanism of hTERT activation provided in this study will be instrumental in designing cancer cell-specific hTERT inhibitors, especially since all the other ways of inhibiting telomerase failed in the clinic.


Assuntos
Neoplasias Colorretais , Telomerase , Humanos , Carcinogênese , Cromatina/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Regiões Promotoras Genéticas , Telomerase/antagonistas & inibidores , Telomerase/genética , Transcrição Gênica
6.
Sci Robot ; 7(69): eabo0235, 2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-36044556

RESUMO

Learning to combine control at the level of joint torques with longer-term goal-directed behavior is a long-standing challenge for physically embodied artificial agents. Intelligent behavior in the physical world unfolds across multiple spatial and temporal scales: Although movements are ultimately executed at the level of instantaneous muscle tensions or joint torques, they must be selected to serve goals that are defined on much longer time scales and that often involve complex interactions with the environment and other agents. Recent research has demonstrated the potential of learning-based approaches applied to the respective problems of complex movement, long-term planning, and multiagent coordination. However, their integration traditionally required the design and optimization of independent subsystems and remains challenging. In this work, we tackled the integration of motor control and long-horizon decision-making in the context of simulated humanoid football, which requires agile motor control and multiagent coordination. We optimized teams of agents to play simulated football via reinforcement learning, constraining the solution space to that of plausible movements learned using human motion capture data. They were trained to maximize several environment rewards and to imitate pretrained football-specific skills if doing so led to improved performance. The result is a team of coordinated humanoid football players that exhibit complex behavior at different scales, quantified by a range of analysis and statistics, including those used in real-world sport analytics. Our work constitutes a complete demonstration of learned integrated decision-making at multiple scales in a multiagent setting.


Assuntos
Futebol Americano , Futebol , Humanos , Aprendizagem , Movimento , Reforço Psicológico , Futebol/fisiologia
7.
Br J Cancer ; 127(5): 800-810, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35484215

RESUMO

Metastasis formation is the main cause of cancer-related death in patients with solid tumours. At the beginning of this process, cancer cells escape from the primary tumour to the blood circulation where they become circulating tumour cells (CTCs). Only a small subgroup of CTCs will survive during the harsh journey in the blood and colonise distant sites. The in-depth analysis of these metastasis-competent CTCs is very challenging because of their extremely low concentration in peripheral blood. So far, only few groups managed to expand in vitro and in vivo CTCs to be used as models for large-scale descriptive and functional analyses of CTCs. These models have shown already the high variability and complexity of the metastatic cascade in patients with cancer, and open a new avenue for the development of new diagnostic and therapeutic approaches.


Assuntos
Células Neoplásicas Circulantes , Biologia , Contagem de Células , Humanos , Metástase Neoplásica , Células Neoplásicas Circulantes/patologia
8.
Clin Exp Metastasis ; 39(1): 21-28, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33961169

RESUMO

The clinical importance of metastatic spread of cancer has been recognized for centuries, and melanoma has loomed large in historical descriptions of metastases, as well as the numerous mechanistic theories espoused. The "fatal black tumor" described by Hippocrates in 5000 BC that was later termed "melanose" by Rene Laennec in 1804 was recognized to have the propensity to metastasize by William Norris in 1820. And while the prognosis of melanoma was uniformly acknowledged to be dire, Samuel Cooper described surgical removal as having the potential to improve prognosis. Subsequent to this, in 1898 Herbert Snow was the first to recognize the potential clinical benefit of removing clinically normal lymph nodes at the time of initial cancer surgery. In describing "anticipatory gland excision," he noted that "it is essential to remove, whenever possible, those lymph glands which first receive the infective protoplasm, and bar its entrance into the blood, before they have undergone increase in bulk". This revolutionary concept marked the beginning of a debate that rages today: are regional lymph nodes the first stop for metastases ("incubator" hypothesis) or does their involvement serve as an indicator of aggressive disease with inherent metastatic potential ("marker" hypothesis). Is there a better way to improve prediction of disease outcome? This article attempts to address some of the resultant questions that were the subject of the session "Novel Frontiers in the Diagnosis of Cancer" at the 8th International Congress on Cancer Metastases, held in San Francisco, CA in October 2019. Some of these questions addressed include the significance of sentinel node metastasis in melanoma, and the optimal method for their pathologic analysis. The finding of circulating tumor cells in the blood may potentially supplant surgical techniques for detection of metastatic disease, and we are beginning to perfect techniques for their detection, understand how to apply the findings clinically, and develop clinical followup treatment algorithms based on these results. Finally, we will discuss the revolutionary field of machine learning and its applications in cancer diagnosis. Computer-based learning algorithms have the potential to improve efficiency and diagnostic accuracy of pathology, and can be used to develop novel predictors of prognosis, but significant challenges remain. This review will thus encompass latest concepts in the detection of cancer metastasis via the lymphatic system, the circulatory system, and the role of computers in enhancing our knowledge in this field.


Assuntos
Melanoma , Linfonodo Sentinela , Neoplasias Cutâneas , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Melanoma/patologia , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia
9.
Cells ; 10(9)2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34571870

RESUMO

In cancer, many analytes can be investigated through liquid biopsy. They play fundamental roles in the biological mechanisms underpinning the metastatic cascade and provide clinical information that can be monitored in real time during the natural course of cancer. Some of these analytes (circulating tumor cells and extracellular vesicles) share a key feature: the presence of a phospholipid membrane that includes proteins, lipids and possibly nucleic acids. Most cell-to-cell and cell-to-matrix interactions are modulated by the cell membrane composition. To understand cancer progression, it is essential to describe how proteins, lipids and nucleic acids in the membrane influence these interactions in cancer cells. Therefore, assessing such interactions and the phospholipid membrane composition in different liquid biopsy analytes might be important for future diagnostic and therapeutic strategies. In this review, we briefly describe some of the most important surface components of circulating tumor cells and extracellular vesicles as well as their interactions, putting an emphasis on how they are involved in the different steps of the metastatic cascade and how they can be exploited by the different liquid biopsy technologies.


Assuntos
Membrana Celular/patologia , Vesículas Extracelulares/patologia , Células Neoplásicas Circulantes/patologia , Animais , Membrana Celular/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Biópsia Líquida/métodos , Células Neoplásicas Circulantes/metabolismo , Fosfolipídeos/metabolismo
10.
Genome Biol ; 21(1): 276, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-33183336

RESUMO

Biological rhythms regulate the biology of most, if not all living creatures, from whole organisms to their constitutive cells, their microbiota, and also parasites. Here, we present the hypothesis that internal and external ecological variations induced by biological cycles also influence or are exploited by cancer cells, especially by circulating tumor cells, the key players in the metastatic cascade. We then discuss the possible clinical implications of the effect of biological cycles on cancer progression, and how they could be exploited to improve and standardize methods used in the liquid biopsy field.


Assuntos
Ritmo Circadiano/fisiologia , Neoplasias/psicologia , Sono/fisiologia , Fenômenos Cronobiológicos , Biópsia Líquida , Neoplasias/genética , Células Neoplásicas Circulantes
11.
Front Oncol ; 10: 1055, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850309

RESUMO

The metastatic cascade describes the process whereby aggressive cancer cells leave the primary tumor, travel through the bloodstream, and eventually reach distant organs to develop one or several metastases. During the last decade, innovative technologies have exploited the recent biological knowledge to identify new circulating biomarkers for the screening and early detection of cancer, real-time monitoring of treatment response, assessment of tumor relapse risk (prognosis), identification of new therapeutic targets and resistance mechanisms, patient stratification, and therapeutic decision-making. These techniques are broadly described using the term of Liquid Biopsy. This field is in constant progression and is based on the detection of circulating tumor cells, circulating free nucleic acids (e.g., circulating tumor DNA), circulating tumor-derived extracellular vesicles, and tumor-educated platelets. The aim of this review is to describe the biological principles underlying the liquid biopsy concept and to discuss how functional studies can expand the clinical applications of these circulating biomarkers.

12.
J Appl Lab Med ; 5(5): 1027-1037, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32845318

RESUMO

The long-term effects of cancer on patient quality of life and its economic burden are important issues that need to be addressed. Therefore, it is critical to assess patient priorities and investigate the value proposition of clinical tests in this field. The minimally invasive liquid biopsy has attracted much attention because it allows serial sampling during cancer progression, and provides valuable biological information on the tumor biology and treatment response through the analysis of analytes in the blood, such as circulating tumor cells (CTCs). To introduce CTC analysis in daily clinical practice, it is still necessary to firmly establish its clinical benefits and extra value for clinical decision-making. A laboratory medicine value proposition of CTC medical applications can help to address these issues. In this review, we discuss the current evidence for a value proposition of CTC detection, isolation, and characterization using the available technologies, and we summarize the unmet requirements for the full integration of CTCs in the care pathway.


Assuntos
Células Neoplásicas Circulantes , Tomada de Decisão Clínica , Humanos , Laboratórios , Biópsia Líquida , Qualidade de Vida
13.
Cells ; 9(8)2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32764280

RESUMO

In the last few decades, the epithelial cell adhesion molecule (EpCAM) has received increased attention as the main membrane marker used in many enrichment technologies to isolate circulating tumor cells (CTCs). Although there has been a great deal of progress in the implementation of EpCAM-based CTC detection technologies in medical settings, several issues continue to limit their clinical utility. The biology of EpCAM and its role are not completely understood but evidence suggests that the expression of this epithelial cell-surface protein is crucial for metastasis-competent CTCs and may not be lost completely during the epithelial-to-mesenchymal transition. In this review, we summarize the most significant advantages and disadvantages of using EpCAM as a marker for CTC enrichment and its potential biological role in the metastatic cascade.


Assuntos
Molécula de Adesão da Célula Epitelial/metabolismo , Células Neoplásicas Circulantes/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Molécula de Adesão da Célula Epitelial/genética , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Terapia de Alvo Molecular , Metástase Neoplásica , Neoplasias/diagnóstico , Neoplasias/patologia , Neoplasias/terapia , Células Neoplásicas Circulantes/metabolismo , Prognóstico
14.
Cancers (Basel) ; 12(4)2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32260071

RESUMO

Metastases and cancer recurrence are the main causes of cancer death. Circulating Tumor Cells (CTCs) and disseminated tumor cells are the drivers of cancer cell dissemination. The assessment of CTCs' clinical role in early metastasis prediction, diagnosis, and treatment requires more information about their biology, their roles in cancer dormancy, and immune evasion as well as in therapy resistance. Indeed, CTC functional and biochemical phenotypes have been only partially characterized using murine metastasis models and liquid biopsy in human patients. CTC detection, characterization, and enumeration represent a promising tool for tailoring the management of each patient with cancer. The comprehensive understanding of CTCs will provide more opportunities to determine their clinical utility. This review provides much-needed insights into this dynamic field of translational cancer research.

15.
Front Oncol ; 10: 120, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117767

RESUMO

There are many risk factors associated with breast cancer (BC) such as the familial history of BC, using hormone replacement therapy, obesity, personal habits, and other clinical factors; however, not all BC cases are attributed to these risk factors. Recent researches show a correlation between patient microbiome and BC suggested as a new risk factor. The present review article aimed at evaluating the role of the microbiome as a risk factor in the occurrence of BC, investigating the proposed mechanisms of interaction between the microbiome and human genes involved in BC, and assessing the impact of the altered composition of breast, gut, and milk microbiome in the physiological status of normal breast as well as cancerous or non-cancerous breast lesions. The study also evaluated the growing evidence that these altered populations may hinder chemotherapeutic treatment. The role of microbiome in the development and maintenance of inflammation, estrogen metabolism, and epigenetic alterations was properly investigated. Finally, clinical and therapeutic applications of the microbiome- e.g., probiotics, microbiome genome modulation, and engineered microbiome enzymes in the management of BC were reviewed.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31548226

RESUMO

The current limitations of cancer diagnosis and molecular profiling based on invasive tissue biopsies or clinical imaging have led to the development of the liquid biopsy field. Liquid biopsy includes the isolation of circulating tumor cells (CTCs), circulating free or tumor DNA (cfDNA or ctDNA), extracellular vesicles (EVs), and tumor-educated platelets (TEPs) from body fluid samples and their molecular characterization to identify biomarkers for early cancer diagnosis, prognosis, therapeutic prediction, and follow-up. These innovative biosources show similar features as the primary tumor from where they originated or interacted. This review describes the different technologies and methods used for processing these biosources as well as their main clinical applications with their advantages and limitations.


Assuntos
Biópsia Líquida/métodos , Neoplasias/diagnóstico , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Detecção Precoce de Câncer , Vesículas Extracelulares/genética , Humanos , Neoplasias/patologia , Células Neoplásicas Circulantes/patologia , Prognóstico
17.
Mol Aspects Med ; 72: 100816, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31377345

RESUMO

Metastasis is the main cause of death in patients with cancer. The molecular mechanisms underlying the different metastasis steps are not yet fully known, partly because most studies have been focusing only on cancer cells within the tumor. Currently, with the development of technologies for the enrichment and capture of circulating tumor cells (CTCs), it is possible to characterize cancer cells at the exact moment of metastasis initiation. Therefore, CTCs are a promising bio-source for real-time liquid biopsies in patients with cancer. However, their exploitation has been hampered by the limited number of CTCs in the bloodstream and the changing phenotype of cancer cells during the metastatic process. Different methods have been developed to expand CTCs in vitro and in vivo (in animal models) with the aim of characterizing functional metastasis-initiator CTCs with stemness traits, and to obtain new diagnostics and therapeutic tools. In this review, we describe how the establishment of in vitro CTC cultures and of CTC-derived xenografts has led to the identification of molecular mechanisms related to metastasis initiation by CTCs, such as epithelial-to-mesenchymal transition (EMT), stemness, and clustering. These models enable the functional analysis and in-depth proteomic, transcriptomic and genomic profiling of metastasis-competent CTCs. We then discuss the relationship between EMT and stem cell features, and how these aspects might interact with other factors in the tumor microenvironment to induce CTC dissemination and proliferation in distant organs.


Assuntos
Biópsia Líquida/métodos , Neoplasias/patologia , Células Neoplásicas Circulantes/patologia , Animais , Biomarcadores Tumorais , Transição Epitelial-Mesenquimal , Feminino , Humanos , Masculino , Medicina de Precisão , Células Tumorais Cultivadas , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Clin Chem ; 66(1): 97-104, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31811001

RESUMO

BACKGROUND: One of the objectives for the liquid biopsy is to become a surrogate to tissue biopsies in diagnosis of cancer as a minimally invasive method, with clinical utility in real-time follow-ups of patients. To achieve this goal, it is still necessary to achieve a better understanding of the mechanisms of cancer and the biological principles that govern its behavior, particularly with regard to circulating tumor cells (CTCs). CONTENT: The isolation, enumeration, detection, and characterization of CTCs have already proven to provide relevant clinical information about patient prognosis and treatment prediction. Moreover, CTCs can be analyzed at the genome, proteome, transcriptome, and secretome levels and can also be used for functional studies in in vitro and in vivo models. These features, taken together, have made CTCs a very valuable biosource. SUMMARY: To further advance the field and discover new clinical applications for CTCs, several studies have been performed to learn more about these cells and better understand the biology of metastasis. In this review, we describe the recent literature on the topic of liquid biopsy with particular focus on the biology of CTCs.


Assuntos
Células Neoplásicas Circulantes/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Biópsia Líquida , Células Neoplásicas Circulantes/patologia , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Proteoma/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Transcriptoma , Proteínas ras/genética
19.
BMC Med Inform Decis Mak ; 19(1): 159, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409338

RESUMO

BACKGROUND: Drug-drug interactions (DDIs) can cause patient harm. Between 46 and 90% of patients admitted to the Intensive Care Unit (ICU) are exposed to potential DDIs (pDDIs). This rate is twice as high as patients on general wards. Clinical decision support systems (CDSSs) have shown their potential to prevent pDDIs. However, the literature shows that there is considerable room for improvement of CDSSs, in particular by increasing the clinical relevance of the pDDI alerts they generate and thereby reducing alert fatigue. However, consensus on which pDDIs are clinically relevant in the ICU setting is lacking. The primary aim of this study is to evaluate the effect of alerts based on only clinically relevant interactions for the ICU setting on the prevention of pDDIs among Dutch ICUs. METHODS: To define the clinically relevant pDDIs, we will follow a rigorous two-step Delphi procedure in which a national expert panel will assess which pDDIs are perceived clinically relevant for the Dutch ICU setting. The intervention is the CDSS that generates alerts based on the clinically relevant pDDIs. The intervention will be evaluated in a stepped-wedge trial. A total of 12 Dutch adult ICUs using the same patient data management system, in which the CDSS will operate, were invited to participate in the trial. Of the 12 ICUs, 9 agreed to participate and will be enrolled in the trial. Our primary outcome measure is the incidence of clinically relevant pDDIs per 1000 medication administrations. DISCUSSION: This study will identify pDDIs relevant for the ICU setting. It will also enhance our understanding of the effectiveness of alerts confined to clinically relevant pDDIs. Both of these contributions can facilitate the successful implementation of CDSSs in the ICU and in other domains as well. TRIAL REGISTRATION: Nederlands Trial register Identifier: NL6762 . Registered November 26, 2018.


Assuntos
Protocolos Clínicos , Interações Medicamentosas , Unidades de Terapia Intensiva , Análise por Conglomerados , Sistemas de Apoio a Decisões Clínicas , Hospitalização , Humanos , Incidência , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
20.
Science ; 360(6394): 1204-1210, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29903970

RESUMO

Scene representation-the process of converting visual sensory data into concise descriptions-is a requirement for intelligent behavior. Recent work has shown that neural networks excel at this task when provided with large, labeled datasets. However, removing the reliance on human labeling remains an important open problem. To this end, we introduce the Generative Query Network (GQN), a framework within which machines learn to represent scenes using only their own sensors. The GQN takes as input images of a scene taken from different viewpoints, constructs an internal representation, and uses this representation to predict the appearance of that scene from previously unobserved viewpoints. The GQN demonstrates representation learning without human labels or domain knowledge, paving the way toward machines that autonomously learn to understand the world around them.


Assuntos
Aprendizado de Máquina , Redes Neurais de Computação , Visão Ocular
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