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1.
Recent Results Cancer Res ; 215: 3-24, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31605221

RESUMO

The traditional model of metastatic progression postulates that the ability to form distant metastases is driven by random mutations in cells of the primary tumor.


Assuntos
Metástase Neoplásica/genética , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Progressão da Doença , Humanos , Mutação
2.
Recent Results Cancer Res ; 215: 89-104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31605225

RESUMO

Circulating tumor cells (CTCs) represent novel biomarkers, since they are obtainable through a simple and noninvasive blood draw or liquid biopsy. Here, we review the high-definition single-cell analysis (HD-SCA) workflow, which brings together modern methods of immunofluorescence with more sophisticated image processing to rapidly and accurately detect rare tumor cells among the milieu of platelets, erythrocytes, and leukocytes in the peripheral blood. In particular, we discuss progress in methods to measure CTC morphology and subcellular protein expression, and we highlight some initial applications that lead to fundamental new insights about the hematogenous phase of cancer, as well as its performance in early-stage diagnosis and treatment monitoring. We end with an outlook on how to further probe CTCs and the unique advantages of the HD-SCA workflow for improving the precision of cancer care.


Assuntos
Biologia Computacional , Neoplasias/patologia , Células Neoplásicas Circulantes/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Ensaios de Triagem em Larga Escala , Humanos , Neoplasias/diagnóstico , Neoplasias/terapia , Células Neoplásicas Circulantes/patologia , Análise de Célula Única
3.
Recent Results Cancer Res ; 215: 105-125, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31605226

RESUMO

Circulating tumour cells (CTCs) constitute a potential tumour surrogate that could serve as "liquid biopsy" with the advantage to be a minimally invasive approach compared to traditional tissue biopsies. As CTCs are thought to be the source of metastatic lesions, their analysis represents a potential means of tracking cancer cells from the primary tumour en route to distant sites, thus providing valuable insights into the metastatic process. However, several problems, such as their rarity in the peripheral blood, the technical limitations of single-cell downstream analysis and their phenotypic variability, make CTC detection and molecular characterisation very challenging. Nevertheless, in the last decade, there has been an exponential increase of interest in the development of powerful cellular and molecular methodologies applied to CTCs. In this chapter, we focus on the recent advances of functional studies and molecular profiling of CTCs. We will also highlight the clinical relevance of CTC detection and enumeration, and discuss their potential as tumour biomarkers with special focus on lung cancer.


Assuntos
Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Células Neoplásicas Circulantes/metabolismo , Biomarcadores Tumorais/análise , Humanos , Células Neoplásicas Circulantes/patologia
4.
Recent Results Cancer Res ; 215: 127-145, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31605227

RESUMO

With active screening for early detection and advancements in treatment, there has been a significant decrease in mortality from breast cancer. However, a significant proportion of patients with non-metastatic breast cancer at time of diagnosis will relapse. Therefore, it is suggested that the dissemination of bloodstream tumor cells (circulating tumor cells, CTCs) undetectable by currently available diagnostic tools occurs during the early stages of breast cancer progression, and may be the potential source of micrometastases responsible for treatment failures. Here, we review the clinical significance of CTCs, as detected by the FDA-approved CellSearch® System, in both metastatic and non-metastatic breast cancer patients. Studies so far suggest that CTCs are prognostic of poorer outcomes in breast cancer patients; however, there is currently insufficient data to support use of CTC data to guide treatment. Therefore, there are ongoing studies to evaluate the utility of assessing CTC phenotypes to develop personalized breast cancer treatment, which will be reviewed in this chapter.


Assuntos
Neoplasias da Mama/patologia , Células Neoplásicas Circulantes/metabolismo , Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Progressão da Doença , Humanos , Células Neoplásicas Circulantes/patologia , Medicina de Precisão , Prognóstico
5.
Recent Results Cancer Res ; 215: 147-160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31605228

RESUMO

The development of metastatic disease accounts for the vast majority of cancer-related deaths in solid tumor malignancies. Distant metastases primarily develop as a result of tumor cell dissemination through the circulatory system.


Assuntos
Neoplasias da Mama/patologia , Metástase Neoplásica/patologia , Células Neoplásicas Circulantes/patologia , Humanos
6.
Anticancer Res ; 39(9): 4711-4720, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519570

RESUMO

BACKGROUND/AIM: Dynamics of circulating tumor cells (CTCs) after molecular targeting therapy remain unclear. MATERIALS AND METHODS: We examined changes in CTC numbers and morphology early after targeting therapy in EGFR-mutated PC-9 human lung cancer and HER2-gene amplified GLM-1 gastric cancer mouse CTC models using a cytology-based semi-automated CTC detection platform. RESULTS: Erlotinib and T-DM1 inhibited cell growth mainly by induction of apoptosis in vitro. The number of CTCs detected 5-10 days after targeting therapy in mice was significantly increased compared to CTC numbers before therapy. The increased CTCs after therapy consisted of apoptotic CTCs and viable CTCs. This heterogeneous population of CTCs reflects well the cell population of the primary tumor disrupted by therapy. CONCLUSION: CTCs can be mobilized from the primary tumor due to tissue disruption in acute response to targeting therapy, suggesting potential usefulness of CTC monitoring as a predictor of therapeutic response in the clinical settings.


Assuntos
Amplificação de Genes , Mutação , Células Neoplásicas Circulantes/metabolismo , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Animais , Antineoplásicos/farmacologia , Biomarcadores , Biomarcadores Tumorais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Receptores ErbB/genética , Cloridrato de Erlotinib/farmacologia , Xenoenxertos , Humanos , Imuno-Histoquímica , Camundongos , Células Neoplásicas Circulantes/patologia , Neoplasias Gástricas/tratamento farmacológico
7.
Anticancer Res ; 39(8): 4061-4064, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366488

RESUMO

BACKGROUND/AIM: Circulating tumor cells (CTCs) may have an important role in metastasis. CTC clusters, which contain fibroblasts, indicate poor prognosis. In the present study, we used our malignant lymphoma metastatic mouse model to compare the effect of a choline-deficient-diet (CDD) and the control diet (CD) on fibroblasts in CTCs. MATERIALS AND METHODS: We compared the number and morphology of CTCs in CDD and CD mice using color-coded imaging with fluorescent proteins. Malignant lymphoma EL4 cells expressing RFP were injected in the spleen of transgenic C57B/6-GFP mice, which were fed a CDD or CD. Two weeks later, we harvested and observed the number of CTCs and fibroblast-like cells both in heart blood and portal blood. Imaging of CTC morphology was performed with smeared glass slides and in culture. RESULTS AND CONCLUSION: There was no significant difference in the number of CTCs between CDD and CD mice. The number of fibroblast-like cells in the CTC microenvironment in CD mouse portal blood was significantly larger than in CDD mouse portal blood. These differences may be caused by deficiency in choline that leads to less metastasis in choline-deficient-diet-induced fatty liver.


Assuntos
Colina/metabolismo , Linfoma/sangue , Células Neoplásicas Circulantes/metabolismo , Células Estromais/metabolismo , Animais , Linhagem Celular Tumoral , Deficiência de Colina/sangue , Deficiência de Colina/genética , Deficiência de Colina/patologia , Dieta/efeitos adversos , Modelos Animais de Doenças , Fibroblastos/metabolismo , Fibroblastos/patologia , Proteínas de Fluorescência Verde/química , Humanos , Proteínas Luminescentes/química , Linfoma/genética , Linfoma/patologia , Camundongos , Camundongos Transgênicos , Metástase Neoplásica , Células Neoplásicas Circulantes/patologia , Células Estromais/patologia , Microambiente Tumoral/genética
8.
Medicine (Baltimore) ; 98(30): e16579, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348291

RESUMO

In this study, we aim to explore the values of serum dickkopf-1 (DKK1) and circulating tumor cells (CTCs) in predicting the efficacy and prognosis of transcatheter arterial chemoembolization (TACE) treatment on patients with hepatocellular carcinoma (HCC). We did a retrospective analysis on 155 HCC patients who underwent TACE treatment. The patients were divided into response group (complete response and partial response) and nonresponse group (stable disease and progressive disease), and their changes in serum DKK1 and CTCs after TACE were recorded. Receiver operating characteristic curve and survival analysis were used to assess the predictive values of DKK1 and CTCs for TACE efficacy and long-term prognosis of HCC. We found that the levels of preoperative DKK1 and CTCs in patients with HCC had a moderate positive correlation (r = 0.54). After TACE treatment, the serum DKK1 and CTCs in the response group were significantly decreased compared to pretreatment levels (P < .05), whereas the nonresponse group showed significantly increased serum DKK1 and CTCs levels (P < .05). The largest area under the curve (AUC) was achieved when using >0.02 µg/L reduction in DKK1 level after 4 weeks of TACE to predict the efficacy of TACE treatment (AUC = 0.913, 95% confidence interval: 0.856-0.952, P < .001), with the sensitivity of 78.26% and the specificity of 88.07%. The overall survival, disease-free survival, and 5-year survival rates were all significantly lower in the patients with positive preoperative levels of serum DKK1 and CTCs. COX multivariate regression analysis showed that Eastern Cooperative Oncology Group score, and preoperative levels of serum DKK1 and CTCs are independent influencing factors for the prognosis of patients with HCC. Overall, our results demonstrated that serum DKK1 and CTCs levels were good biomarkers for predicting the efficacy and prognosis of TACE treatment in patients with HCC. Moreover, these parameters exhibited different characteristics, and might have different potential applications.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Neoplasias Hepáticas/terapia , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Curva ROC , Estudos Retrospectivos
9.
Int J Nanomedicine ; 14: 4187-4209, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31289440

RESUMO

Circulating tumor cells (CTCs) are disseminated cancer cells. The occurrence and circulation of CTCs seem key for metastasis, still the major cause of cancer-associated deaths. As such, CTCs are investigated as predictive biomarkers. However, due to their rarity and heterogeneous biology, CTCs' practical use has not made it into the clinical routine. Clearly, methods for the effective isolation and reliable detection of CTCs are urgently needed. With the development of nanotechnology, various nanosystems for CTC isolation and enrichment and CTC-targeted cancer therapy have been designed. Here, we summarize the relationship between CTCs and tumor metastasis, and describe CTCs' unique properties hampering their effective enrichment. We comment on nanotechnology-based systems for CTC isolation and recent achievements in microfluidics and lab-on-a-chip technologies. We discuss recent advances in CTC-targeted cancer therapy exploiting the unique properties of nanomaterials. We conclude by introducing developments in CTC-directed nanosystems and other advanced technologies currently in (pre)clinical research.


Assuntos
Biomarcadores Tumorais/análise , Separação Celular/métodos , Nanomedicina/métodos , Células Neoplásicas Circulantes/patologia , Biomarcadores Tumorais/isolamento & purificação , Materiais Biomiméticos , Grafite , Humanos , Dispositivos Lab-On-A-Chip , Microfluídica/instrumentação , Microfluídica/métodos , Nanoestruturas/química , Nanotecnologia/métodos , Nanotubos de Carbono
11.
Cancer Sci ; 110(9): 2773-2782, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31348594

RESUMO

Characterization of circulating tumor cells (CTC) is important to prevent death caused by the metastatic spread of cancer cells because CTC are associated with distal metastasis and poor prognosis of breast cancer. We have previously developed suspension cells (SC) using breast cancer cell lines and demonstrated their high metastatic potential. As survival of CTC is highly variable from a few hours to decades, herein we cultured SC for an extended time and named them adapted suspension cells (ASC). Silent mating-type information regulation 2 homolog 1 (SIRT1) expression increased in ASC, which protected the cells from apoptosis. High SIRT1 expression was responsible for the suppression of nuclear factor kappa B (NF-κB) activity and downregulation of reactive oxygen species (ROS) in ASC. As the inhibition of NF-κB and ROS production in SIRT1-depleted ASC contributed to the development of resistance to apoptotic cell death, maintenance of a low ROS level and NF-κB activity in ASC is a crucial function of SIRT1. Thus, SIRT1 overexpression may play an important role in growth adaptation of SC because SIRT1 expression is increased in long-term rather than in short-term cultures.


Assuntos
Neoplasias da Mama/patologia , Sobrevivência Celular , Células Neoplásicas Circulantes/patologia , Sirtuína 1/metabolismo , Animais , Apoptose , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Cancer Res Clin Oncol ; 145(8): 2071-2082, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154543

RESUMO

PURPOSE: Fluorescence in situ hybridization (FISH) using tumor tissue is the gold standard for detection of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC). However, this method often is not repeatable due to difficulties in the acquisition of tumor tissues. Blood-based liquid biopsy using reverse transcription polymerase chain reaction (RT-PCR) is expected to be useful to overcome this limitation. Here, we investigated the feasibility of liquid biopsy using plasma and platelets for detection of ALK rearrangement and prediction of ALK inhibitor treatment outcomes. METHODS: ALK-FISH assays were performed in 1128 tumor specimens of NSCLC between January 2015 and June 2018. We retrospectively analyzed formalin-fixed paraffin-embedded (FFPE) tissues from previously confirmed FISH-positive (n = 199) and -negative (n = 920) cases. We recruited patients who had available tissue specimens and agreed to venous sampling. RNA was extracted from FFPE blocks, plasma, and platelets. Fusion RNA of echinoderm microtubule-associated protein-like 4 (EML4)-ALK was detected by quantitative PCR. RESULTS: Thirty-three FISH-positive and 28 FISH-negative patients were enrolled. In validation, data compared with FISH, RT-PCR using FFPE tissues showed 54.5% sensitivity, 78.6% specificity, and 75.5% accuracy. Liquid biopsy had higher sensitivity (78.8%), specificity (89.3%) and accuracy (83.6%). Higher positivity for liquid biopsy was shown in subgroups with delayed (≥ 6 months from diagnosis) blood sampling (plasma, 85.7%; platelets, 87.0%). In 26 patients treated with crizotinib, the platelet-positive subgroup showed longer median duration of treatment (7.2 versus 1.5 months), longer median progression-free survival (5.7 months versus 1.7 months), a higher overall response rate (70.6% versus 11.1%), and a higher disease control rate (88.2% versus 44.4%) than the platelet-negative subgroup. CONCLUSION: Liquid biopsy could have applications in the diagnosis of ALK-positive NSCLC, even when using RT-PCR, and platelets can be useful for predicting treatment outcomes of ALK inhibitors.


Assuntos
Quinase do Linfoma Anaplásico/genética , Plaquetas/química , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Análise Mutacional de DNA/métodos , Neoplasias Pulmonares/diagnóstico , Plasma/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Química do Sangue/métodos , Plaquetas/patologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , DNA de Neoplasias/análise , Resistencia a Medicamentos Antineoplásicos/genética , Estudos de Viabilidade , Feminino , Humanos , Hibridização in Situ Fluorescente , Biópsia Líquida , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Células Neoplásicas Circulantes/patologia , Plasma/citologia , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Sensibilidade e Especificidade
13.
Cancer Sci ; 110(8): 2590-2599, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31169336

RESUMO

Liquid biopsy of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) is gaining attention as a method for real-time monitoring in cancer patients. Conventional methods based upon epithelial cell adhesion molecule (EpCAM) expression have a risk of missing the most aggressive CTC subpopulations due to epithelial-mesenchymal transition and may, thus, underestimate the total number of actual CTC present in the bloodstream. Techniques utilizing a label-free inertial microfluidics approach (LFIMA) enable efficient capture of CTC without the need for EpCAM expression. In this study, we optimized a method for analyzing genetic alterations using next-generation sequencing (NGS) of extracted ctDNA and CTC enriched using an LFIMA as a first-phase examination of 30 patients with head and neck cancer, esophageal cancer, gastric cancer and colorectal cancer (CRC). Seven patients with advanced CRC were enrolled in the second-phase examination to monitor the emergence of alterations occurring during treatment with epidermal growth factor receptor (EGFR)-specific antibodies. Using LFIMA, we effectively captured CTC (median number of CTC, 14.5 cells/mL) from several types of cancer and detected missense mutations via NGS of CTC and ctDNA. We also detected time-dependent genetic alterations that appeared during anti-EGFR therapy in CTC and ctDNA from CRC patients. The results of NGS analyses indicated that alterations in the genomic profile revealed by the liquid biopsy could be expanded by using a combination of assays with CTC and ctDNA. The study was registered with the University Hospital Medical Information Network Clinical Trials Registry (ID: UMIN000014095).


Assuntos
DNA Tumoral Circulante/genética , DNA de Neoplasias/genética , Neoplasias/genética , Neoplasias/patologia , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Molécula de Adesão da Célula Epitelial/genética , Transição Epitelial-Mesenquimal/genética , Receptores ErbB/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Biópsia Líquida/métodos , Masculino , Pessoa de Meia-Idade , Mutação/genética
14.
Clin Exp Med ; 19(3): 271-279, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31190187

RESUMO

Overview the progress of liquid biopsy using circulating tumor cells (CTCs) and circulating cell-free tumor DNA (cfDNA) to detect and monitor breast cancer. Based on numerous research efforts, the potential value of CTCs and cfDNA in the clinical aspects of cancer has become clear. With the development of next-generation sequencing analysis and newly developed technologies, many technical issues have been resolved, making liquid biopsy widely used in clinical practice. They can be powerful tools for dynamic monitoring of tumor progression and therapeutic efficacy. In the field of breast cancer, liquid biopsy is a research hot spot in recent years, playing a key role in monitoring breast cancer metastasis, predicting disease recurrence and assessing clinical drug resistance. Liquid biopsy has the advantages of noninvasive, high sensitivity, high specificity and real-time dynamic monitoring. Still application is far from reality, but the research and application prospects of CTCs and cfDNA in breast cancer are still worth exploring and discovering. This article reviews the main techniques and applications of CTCs and cfDNA in breast cancer.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , DNA Tumoral Circulante/análise , Biópsia Líquida/métodos , Células Neoplásicas Circulantes/patologia , Pesquisa Biomédica/tendências , Feminino , Humanos , Biópsia Líquida/tendências , Sensibilidade e Especificidade
15.
Talanta ; 202: 230-236, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31171175

RESUMO

Rapid and non-destructive detection of circulating tumor cells (CTCs) with no disruption of their functions is of great significance for clinical tumor therapy. However, many existing methods for CTC detection commonly rely on conventional three-color immunofluorescence identification, which damages CTCs and easily causes loss of cells. Here, we employed a method to simultaneously capture and authenticate CTCs based on immunonanocomposites (ZnS:Mn2+ QDs and Fe3O4/SiO2) equipped with permanent fluorescent and magnetic properties. A multifunctional nanocomposite was synthesized by encapsulating ZnS:Mn2+ quantum dots (QDs) and Fe3O4 nanoparticles into SiO2 nanospheres and bio-conjugating tumor-specific anti-EpCAM antibodies onto the surface. The resulting nanocomposite had a high tumor cell binding ability, and the Fe3O4 nanoparticles had a rapid magnetic response that enabled capture of circulating tumor cells from patients' blood within minutes. In addition, the cell-immunonanocomposites complexes could be directly recognized by the yellow-orange light emitted by the ZnS:Mn2+ quantum dots, thus labeling cells without utilizing the complicated and destructive procedures involved in traditional CTCs identification. We successfully achieved a high capture efficiency of up to 90.8%, and the specific fluorescence labeling of CTCs was realized in 9 clinical breast cancer patients' samples. Furthermore, this simple, convenient and cell-friendly approach is significant for solving the problems of cell viability and enables non-destructive CTC detection, which marks an advance in cancer treatment and clinical applications.


Assuntos
Nanopartículas de Magnetita/química , Manganês/química , Células Neoplásicas Circulantes/patologia , Pontos Quânticos/química , Sulfetos/química , Compostos de Zinco/química , Linhagem Celular , Humanos , Tamanho da Partícula , Propriedades de Superfície
16.
Hematol Oncol ; 37 Suppl 1: 70-74, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31187522

RESUMO

ctDNA provides an important new strategy that will aid in the treatment of non-Hodgkin's lymphoma. Immunoglobulin sequencing provides a tumor specific marker for disease activity with a sensitivity equivalent to one tumor cell per 10-6. Furthermore, it can provide an estimate of tumor bulk and tumor response dynamics during treatment. Interim monitoring can identify patients at high risk of treatment failure and surveillance monitoring can identify patients months before radiographic disease progression. Tumor specific mutations can also be detected in ctDNA and may reflect an averaging of mutations present within multiple tumor masses. Such analysis may aid in the molecular characterization of tumors and selection of targeted treatments for precision medicine.


Assuntos
Biópsia Líquida , Linfoma não Hodgkin/diagnóstico , Biomarcadores Tumorais , DNA Tumoral Circulante , Humanos , Biópsia Líquida/métodos , Linfoma não Hodgkin/etiologia , Linfoma não Hodgkin/terapia , Técnicas de Diagnóstico Molecular , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia
17.
Acta Cytol ; 63(6): 449-455, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091522

RESUMO

Liquid biopsy provides the opportunity of detecting, analyzing and monitoring cancer in various body effluents such as blood or urine instead of a fragment of cancer tissue. It is composed of different biological matrices such as circulating tumor cells (CTCs), cell free nucleic acids, exosomes or tumors "educated platelets." In addition to representing a non- or minimally invasive procedure, it should represent a better view of tumor heterogeneity and allows for real-time monitoring of cancer evolution. Recent technological and molecular advances, greatly facilitated by the use of microfluidics in many cases, have permitted large progresses both in our ability to purify and analyze liquid biopsy components. In particular, the great developments of droplet-based digital PCR and the various optimizations of next generation sequencing technologies are central to the several validations of CTC-free DNA as a strong cancer biomarker. However, complete adoption of liquid biopsy in clinics will require pursuing recent efforts in the standardization of procedures both on the pre-analytical and analytical aspects.


Assuntos
Biomarcadores Tumorais/análise , DNA Tumoral Circulante/sangue , Biópsia Líquida/métodos , Recidiva Local de Neoplasia/diagnóstico , Neoplasias/diagnóstico , Células Neoplásicas Circulantes/química , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/isolamento & purificação , Biópsia por Agulha Fina , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/isolamento & purificação , DNA Tumoral Circulante/isolamento & purificação , Exossomos/química , Humanos , Biópsia Líquida/normas , Monitorização Fisiológica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Células Neoplásicas Circulantes/patologia
18.
J Nanobiotechnology ; 17(1): 71, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31133019

RESUMO

The incidence of lung cancer continues to rise worldwide. Because the aggressive metastasis of lung cancer cells is the major drawback of successful therapies, the crucial challenge of modern nanomedicine is to develop diagnostic tools to map the molecular mechanisms of metastasis in lung cancer patients. In recent years, microfluidic platforms have been given much attention as tools for novel point-of-care diagnostic, an important aspect being the reconstruction of the body organs and tissues mimicking the in vivo conditions in one simple microdevice. Herein, we present the first comprehensive overview of the microfluidic systems used as innovative tools in the studies of lung cancer metastasis including single cancer cell analysis, endothelial transmigration, distant niches migration and finally neoangiogenesis. The application of the microfluidic systems to study the intercellular crosstalk between lung cancer cells and surrounding tumor microenvironment and the connection with multiple molecular signals coming from the external cellular matrix are discussed. We also focus on recent breakthrough technologies regarding lab-on-chip devices that serve as tools for detecting circulating lung cancer cells. The superiority of microfluidic systems over traditional in vitro cell-based assays with regard to modern nanosafety studies and new cancer drug design and discovery is also addressed. Finally, the current progress and future challenges regarding printable and paper-based microfluidic devices for personalized nanomedicine are summarized.


Assuntos
Neoplasias Pulmonares/diagnóstico , Técnicas Analíticas Microfluídicas/métodos , Nanoestruturas/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Materiais Biomiméticos/química , Movimento Celular , Humanos , Dispositivos Lab-On-A-Chip , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/patologia , Técnicas Analíticas Microfluídicas/instrumentação , Nanomedicina , Nanoestruturas/efeitos adversos , Metástase Neoplásica , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Nanomedicina Teranóstica , Microambiente Tumoral
19.
Nat Commun ; 10(1): 2163, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092822

RESUMO

Molecular analysis of circulating tumor cells (CTCs) at single-cell resolution offers great promise for cancer diagnostics and therapeutics from simple liquid biopsy. Recent development of massively parallel single-cell RNA-sequencing (scRNA-seq) provides a powerful method to resolve the cellular heterogeneity from gene expression and pathway regulation analysis. However, the scarcity of CTCs and the massive contamination of blood cells limit the utility of currently available technologies. Here, we present Hydro-Seq, a scalable hydrodynamic scRNA-seq barcoding technique, for high-throughput CTC analysis. High cell-capture efficiency and contamination removal capability of Hydro-Seq enables successful scRNA-seq of 666 CTCs from 21 breast cancer patient samples at high throughput. We identify breast cancer drug targets for hormone and targeted therapies and tracked individual cells that express markers of cancer stem cells (CSCs) as well as of epithelial/mesenchymal cell state transitions. Transcriptome analysis of these cells provides insights into monitoring target therapeutics and processes underlying tumor metastasis.


Assuntos
Neoplasias da Mama/patologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Células Neoplásicas Circulantes/patologia , Células-Tronco Neoplásicas/patologia , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/isolamento & purificação , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Linhagem Celular , Transição Epitelial-Mesenquimal , Feminino , Perfilação da Expressão Gênica/instrumentação , Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/instrumentação , Ensaios de Triagem em Larga Escala/instrumentação , Ensaios de Triagem em Larga Escala/métodos , Humanos , Biópsia Líquida/instrumentação , Biópsia Líquida/métodos , Camundongos , Análise de Sequência de RNA/instrumentação , Análise de Sequência de RNA/métodos , Análise de Célula Única/instrumentação , Análise de Célula Única/métodos
20.
Medicine (Baltimore) ; 98(20): e15354, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096435

RESUMO

Circulating tumor cells (CTCs) have received enormous attention as a novel biomarker in various malignant diseases. We investigated the clinical association between the presence of perioperative CTCs and survival outcomes in women with ovarian cancer. In a total of 30 women who were scheduled to undergo a surgical treatment for ovarian cancer, peripheral blood samples were obtained before and after surgery. CTCs were isolated and counted using the optimized tapered-slit filter (TSF) platform. The association between the presence of perioperative CTCs and tumor features was evaluated. The impact of the presence of perioperative CTCs on progression-free survival (PFS) and overall survival (OS) rates were analyzed using a Kaplan-Meier method. The median age was 58 (range, 24-77) years, and the median follow-up period was 31.5 (range, 1-41) months. Overall, the CTC detection rate was not significantly different before and after surgery (76.7% vs 57.1%, P = .673). The presence of postoperative CTCs was not significantly associated with 3-year PFS (29.1% vs 58.3%, P = .130) and OS (84.4% vs 80.0%, P = .559) rates in the whole study population. In advanced stage, PFS rate in patients with postoperative CTCs had lower PFS rates than those without postoperative CTCs, although there was no statistical significance (18.8% vs 57.1%, P = .077). Postoperative CTC was more frequently detected in women who had lymph node involvement than those who did not (7/7 [100%] vs 3/10 [30.0%], P = .010). The presence of postoperative CTCs as detected using the TSF platform seems to be associated with poorer PFS rates in women with ovarian cancer of advanced stage. Further study with a larger population is warranted to validate our study findings.


Assuntos
Biomarcadores Tumorais/metabolismo , Células Neoplásicas Circulantes/metabolismo , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Antígeno Ca-125/metabolismo , Feminino , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Período Perioperatório , Período Pós-Operatório , Prognóstico , Intervalo Livre de Progressão , Estudos Prospectivos
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