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1.
Methods Mol Biol ; 2265: 235-245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704719

RESUMO

Circulating tumor cells (CTCs) are cancer cells shed by the primary tumor or its metastases that circulate in the peripheral blood. CTCs are potential seeds for metastases, and their detection may allow early uncovering of metastatic dissemination and disease prognostication. To fully ascertain the biomarker potential of melanoma CTCs, sensitive and reliable methods are required. Melanoma-specific transcript analysis has been widely utilized as a standard approach for measuring the presence of CTCs. Here we describe a method for the analysis of CTCs through the detection of specific transcripts in CTC-enriched fractions.


Assuntos
Biomarcadores Tumorais/sangue , Melanoma/sangue , Células Neoplásicas Circulantes/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/métodos , Biomarcadores Tumorais/genética , DNA/sangue , DNA/isolamento & purificação , Humanos , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patologia , Células Neoplásicas Circulantes/patologia , RNA/sangue , RNA/isolamento & purificação
2.
Methods Mol Biol ; 2265: 265-276, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704721

RESUMO

Liquid biopsy has emerged as the next generation target for diagnostics and therapeutic monitoring of many diseases including cancer. Liquid biopsy offers noninvasive analysis of aberrant biomolecular changes (e.g., aberrant protein expression, DNA mutation) which can provide crucial information on disease stages and therapy responses. As a diagnostically important biomarker for melanoma, the detection of the BRAFV600E aberration at the DNA and protein level in liquid biopsies confers an attractive option. This method describes the preparation and operation of an integrated multimolecular sensor (IMMS) for simultaneous detection of the BRAFV600E aberration in both molecular forms from circulating melanoma cells in liquid biopsy. IMMS integrates specific melanoma cell capture, cell release, cell lysis, and electrochemical BRAFV600E detection on a single device. IMMS is demonstrated for a sample-to-answer workflow of plasma spiked with melanoma cells.


Assuntos
Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Dispositivos Lab-On-A-Chip , Melanoma/metabolismo , Microfluídica/instrumentação , Microfluídica/métodos , Proteínas Proto-Oncogênicas B-raf/metabolismo , Neoplasias Cutâneas/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Técnicas Biossensoriais/instrumentação , Técnicas de Cultura de Células/métodos , Humanos , Imunoensaio/instrumentação , Biópsia Líquida/métodos , Melanoma/genética , Melanoma/patologia , Mutação , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia
3.
Methods Mol Biol ; 2265: 363-376, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704727

RESUMO

The lymph node microenvironment is extremely dynamic and responds to immune stimuli in the host by reprogramming immune, stromal, and endothelial cells. In normal physiological conditions, the lymph node will initiate an appropriate immune response to clear external threats that the host may experience. However, in metastatic disease, cancer cells often colonize local lymph nodes, disrupt immune function, and even leave the lymph node to create additional metastases. Understanding how cancer cells enter, colonize, survive, proliferate, and interact with other cell types in the lymph node is challenging. Here, we describe the use of photoconvertible fluorescent proteins to label and trace the fate of cancer cells once they enter the lymph node.


Assuntos
Rastreamento de Células , Proteínas de Fluorescência Verde/metabolismo , Linfonodos , Neoplasias Experimentais , Células Neoplásicas Circulantes , Imagem Óptica , Animais , Linhagem Celular Tumoral , Humanos , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática , Camundongos , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Microambiente Tumoral
4.
Methods Mol Biol ; 2265: 417-425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704731

RESUMO

Cancer mortality rates are primarily a result of cancer metastasis. Recent advances in microscopy technology allow for the imaging of circulating tumor cells (CTCs) as they extravasate (exit) blood vessels, a key step in the metastasis process. Here, we describe the use of intravital microscopy techniques to image and isolate both extravasating melanoma CTCs and the extravasation-participating endothelial cells. These techniques can be used as a means to study cancer metastasis and as a screening tool for anticancer therapeutics.


Assuntos
Células Endoteliais , Microscopia Intravital , Melanoma Experimental , Células Neoplásicas Circulantes , Peixe-Zebra , Animais , Animais Geneticamente Modificados , Linhagem Celular Tumoral , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Metástase Neoplásica , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia
5.
Int J Mol Sci ; 22(4)2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33562270

RESUMO

Esophageal cancer (EC) is a life-threatening disease, demanding the discovery of new biomarkers and molecular targets for precision oncology. Aberrantly glycosylated proteins hold tremendous potential towards this objective. In the current study, a series of esophageal squamous cell carcinomas (ESCC) and EC-derived circulating tumor cells (CTCs) were screened by immunoassays for the sialyl-Tn (STn) antigen, a glycan rarely expressed in healthy tissues and widely observed in aggressive gastrointestinal cancers. An ESCC cell model was glycoengineered to express STn and characterized in relation to cell proliferation and invasion in vitro. STn was found to be widely present in ESCC (70% of tumors) and in CTCs in 20% of patients, being associated with general recurrence and reduced survival. Furthermore, STn expression in ESCC cells increased invasion in vitro, while reducing cancer cells proliferation. In parallel, an ESCC mass spectrometry-based proteomics dataset, obtained from the PRIDE database, was comprehensively interrogated for abnormally glycosylated proteins. Data integration with the Target Score, an algorithm developed in-house, pinpointed the glucose transporter type 1 (GLUT1) as a biomarker of poor prognosis. GLUT1-STn glycoproteoforms were latter identified in tumor tissues in patients facing worst prognosis. Furthermore, healthy human tissues analysis suggested that STn glycosylation provided cancer specificity to GLUT1. In conclusion, STn is a biomarker of worst prognosis in EC and GLUT1-STn glycoforms may be used to increase its specificity on the stratification and targeting of aggressive ESCC forms.


Assuntos
Antígenos Glicosídicos Associados a Tumores/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Transportador de Glucose Tipo 1/metabolismo , Proteoma/análise , Software , Antígenos Glicosídicos Associados a Tumores/química , Apoptose , Proliferação de Células , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Regulação Neoplásica da Expressão Gênica , Transportador de Glucose Tipo 1/química , Glicosilação , Humanos , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Células Tumorais Cultivadas
6.
Methods Mol Biol ; 2235: 181-190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33576978

RESUMO

Tumor progression and metastasis are multistep processes that are critically dependent on the interaction of metastasizing tumor cells with other cells of the local microenvironment. Mimicking the single steps of the metastatic cascade in vitro is therefore challenging when investigating not only tumor cell behavior alone but also cellular crosstalk between different cell populations. In particular, the crosstalk of tumor cells with pericytes and endothelial cells when accessing the bloodstream is of great importance for successful intravasation and metastatic dissemination. To examine metastatic intravasation and analyze the interaction of tumor cells with pericytes, which reside within the basement membrane and endothelial cells, aligning the vessel wall, we have designed a 3D in vitro transwell assay mimicking tumor cell intravasation into a vessel. Modifying the Boyden chamber transwell assay by seeding first an endothelial cell layer onto the transwell membrane and covering it with pericytes before adding the tumor cells allows us to investigate the role of pericytes and endothelial cells on tumor cell intravasation and at the same time to study their crosstalk at the molecular level and how this interaction influences tumor cell behavior. It further allows the manipulation of the system for proof-of-principle experimentation.


Assuntos
Técnicas de Cultura de Células/métodos , Invasividade Neoplásica/patologia , Pericitos/metabolismo , Animais , Membrana Basal , Biomimética , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos , Metástase Neoplásica/patologia , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Pericitos/patologia , Microambiente Tumoral
7.
Anticancer Res ; 41(2): 885-893, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517294

RESUMO

BACKGROUND/AIM: Circulating tumor cells (CTCs) may be affected by the environment encountered during blood circulation. We aimed to explore the association between the molecular phenotype of CTCs and systemic inflammatory markers. PATIENTS AND METHODS: CTCs isolated from patients with recurrent/metastatic head and neck squamous cell carcinoma by CD45-negative selection were analyzed for the expression of multiple genes. The correlations between gene expression levels in CTCs and systemic inflammation markers were examined. RESULTS: Thirty-five (83.3%) of the 42 patients were positive for CTCs. No significant differences in systemic inflammatory markers were observed between CTC-positive and CTC-negative patients. Notably, VIM or ZEB2 expression was strongly correlated with that of CD44 or ALDH1. PIK3CA, CD44, ALDH1A1, and PDCD1LG2 expression in CTCs was correlated with lymphocyte- and/or albumin-related systemic inflammatory markers. CONCLUSION: CTCs acquire a survival advantage through phenotypic alterations in the hostile blood environment, and evade circulatory immune surveillance.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Recidiva Local de Neoplasia/metabolismo , Células Neoplásicas Circulantes/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Idoso , Idoso de 80 Anos ou mais , Transição Epitelial-Mesenquimal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Análise de Sobrevida , Evasão Tumoral , Microambiente Tumoral
8.
Nat Rev Cancer ; 21(3): 162-180, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33462499

RESUMO

Metastasis formation is the major cause of death in most patients with cancer. Despite extensive research, targeting metastatic seeding and colonization is still an unresolved challenge. Only recently, attention has been drawn to the fact that metastasizing cancer cells selectively and dynamically adapt their metabolism at every step during the metastatic cascade. Moreover, many metastases display different metabolic traits compared with the tumours from which they originate, enabling survival and growth in the new environment. Consequently, the stage-dependent metabolic traits may provide therapeutic windows for preventing or reducing metastasis, and targeting the new metabolic traits arising in established metastases may allow their eradication.


Assuntos
Metástase Neoplásica , Neoplasias/metabolismo , Acetatos/metabolismo , Trifosfato de Adenosina/biossíntese , Animais , Plasticidade Celular , Ácidos Graxos/metabolismo , Glutamina/metabolismo , Humanos , Ácido Láctico/metabolismo , Neoplasias/patologia , Células Neoplásicas Circulantes/metabolismo , Ácido Pirúvico/metabolismo
9.
Neurosurgery ; 88(3): E221-E230, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33442748

RESUMO

Accurate circulating biomarkers have potential clinical applications in population screening, tumor subclassification, monitoring tumor status, and the delivery of individualized treatments resulting from tumor genotyping. Recently, significant progress has been made within this field in several cancer types, but despite the many potential benefits, currently there is no validated circulating biomarker test for patients with glioma. A number of circulating factors have been examined, including circulating tumor cells, cell-free DNA, microRNA, exosomes, and proteins from both peripheral blood and cerebrospinal fluid with variable results. In the following article, we provide a narrative review of the current evidence pertaining to circulating biomarkers in patients with glioma, including discussion of the advantages and challenges encountered with the current methods used for discovery. Additionally, the potential clinical applications are described with reference to the literature.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/sangue , Glioma/sangue , Células Neoplásicas Circulantes/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Exossomos/metabolismo , Exossomos/patologia , Glioma/patologia , Humanos , MicroRNAs/sangue , MicroRNAs/metabolismo , Células Neoplásicas Circulantes/patologia
10.
Anticancer Res ; 41(2): 661-670, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517270

RESUMO

BACKGROUND: To investigate the correlation between circulating tumor cells (CTCs) bearing cancer stem cell (CSC) and epithelial-to-mesenchymal (EMT) phenotypes and the different immunosuppressive cells in peripheral blood of patients with metastatic breast cancer (mBC). MATERIALS AND METHODS: Blood was obtained from 38 pre-treated patients with mBC before a new line of treatment. CTC detection and characterization was performed by triple immunofluorescent staining, while Myeloid-derived Suppressor Cells (MDSCs) and T regulatory cells (Tregs) were analyzed by multi-flow cytometry. RESULTS: CTCs were detected in 16 (42.1%) of patients. Based on the co-expression of ALDH1, TWIST and CK, CTCs revealed an important heterogeneity: CTCs with a CSC/partial-EMT, CSC/Epithelial-like, non-CSC/partial-EMT and non-CSC/Epithelial-like phenotype were detected in 7 (18.4%), 7 (18.4%), 1 (1.4%) and 9 (23.7%) of patients, respectively. Immunophenotyping of MDSCs identified 2 monocytic [M-MDSCs; CD14+CD15+CD11b+CD33+HLA-DR-Lin- (CD14+CD15+) and CD14+CD15-CD11b+CD33+ HLA-DR-Lin- (CD14+CD15-)] and one granulocytic [G-MDSCs; CD14-CD15+CD11b+CD33+HLA-DR-Lin- (CD14- CD15+)] subpopulations, expressing inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS), respectively. Patients with detectable CTCs had a higher frequency of Tregs (CD3+CD4+CD25high; p=0.022) whereas a positive correlation was found between CTC counts and the percentage of Tregs (p=0.005) and CD14+CD15+ M-MDSCs (p=0.024). Patients with a partial-EMT phenotype had a higher frequency of CD14+CD15+ M-MDSCs (p=0.023). Patients harboring the non-CSC/epithelial-like CTC subpopulation had an increased frequency of CD14-CD15+ G-MDSCs (p=0.020), along with decreased levels of CD3+CD4+CD25high FoxP3+ Tregs (p=0.020). CONCLUSION: These findings provide evidence that CTCs in ER+/HER2- mBC patients may be under the control of the immune system and various immune escape mechanisms might be involved during the different stages of their biological evolution.


Assuntos
Neoplasias da Mama/imunologia , Transição Epitelial-Mesenquimal , Células Supressoras Mieloides/imunologia , Células Neoplásicas Circulantes/imunologia , Células-Tronco Neoplásicas/imunologia , Linfócitos T Reguladores/imunologia , Evasão Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Pessoa de Meia-Idade , Células Supressoras Mieloides/metabolismo , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fenótipo , Linfócitos T Reguladores/metabolismo
11.
Methods Mol Biol ; 2195: 245-261, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32852768

RESUMO

While the majority of patients with advanced testicular germ cell tumors (GCT) achieve complete responses after chemotherapy and if indicated after postchemotherapy resection of residual lesions, about 20% of patients have incomplete responses or show relapses. Moreover, toxicity of chemotherapy is high, and severe adverse chronic effects have been described. Therefore, there is an urgent need for biomarkers that could help to improve tumor staging, and support decision-making, ideally including monitoring of therapy response and prediction of relapse. Besides the well-established serum markers lactate dehydrogenase, α-fetoprotein, and ß-subunit of human chorionic gonadotropin, during recent years new noninvasive liquid biopsy markers have been investigated in GCT, including cell-free nucleic acids like microRNAs, and circulating tumor cells (CTCs).Prognostic relevance has been demonstrated for circulating tumor cells (CTCs) in patients with different cancers. However, little is known in GCT patients. Histologically, GCT are a very heterogeneous group of tumors comprising pure seminomas (consisting of cells that remember primordial germ cells) and nonseminomas, which are either undifferentiated (embryonal carcinoma) or differentiated, exhibiting different degrees of embryonic (teratoma) or extraembryonic (yolk sac tumor and choriocarcinoma) differentiation. This heterogeneity hampers capture and detection of CTCs deriving from those tumors using a single method or a single antibody. To date, label-independent capture methods that enrich tumor cells according to the density of GCT cells, which is similar to that of mononuclear cells, have been successfully applied. Since testicular GCT might also express epithelial proteins, methods based on enrichment of CTCs using epithelial markers are promising to detect CTCs in certain subgroups of patients with GCTs as well.Here, we describe and discuss a combination of methods to capture and detect GCT cells with epithelial and germ cell characteristics in blood.


Assuntos
Biomarcadores Tumorais , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/etiologia , Células Neoplásicas Circulantes/patologia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/etiologia , Linhagem Celular Tumoral , Separação Celular/métodos , Células Cultivadas , Imunofluorescência , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Biópsia Líquida , Masculino , Técnicas de Diagnóstico Molecular , Células Neoplásicas Circulantes/metabolismo , Prognóstico
12.
Biomed Pharmacother ; 134: 111153, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33360045

RESUMO

Cancer metastasis is one of the foremost causes of cancer incidence and fatality in the whole of the world. Circulating tumor cells (CTC) have been confirmed to be among the most significant stimuli of metastasis in recent years and presently are the subject of extensive research aiming to be accurately identified by using biological and physical properties. Among the various studies conducted for isolation, identification, and characterization of CTCs, microfluidic systems have aroused great attention owing to their unique advantages such as low-cost, simplicity, reduction in reagent consumption, miniaturization, fast and precise control. The purpose of this review is to provide an overview of current state of the microfluidic biosensors for the screening of CTCs. Additionally, given the recent progress in this field, future outlook for the development of the microfluidics biosensing is briefly discussed.


Assuntos
Biomarcadores Tumorais/sangue , Técnicas Biossensoriais , Detecção Precoce de Câncer , Técnicas Analíticas Microfluídicas , Neoplasias/diagnóstico , Células Neoplásicas Circulantes/metabolismo , Animais , Separação Celular , Humanos , Metástase Neoplásica , Neoplasias/sangue , Neoplasias/patologia , Células Neoplásicas Circulantes/patologia , Valor Preditivo dos Testes , Prognóstico
13.
PLoS One ; 15(12): e0243928, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33338056

RESUMO

BACKGROUND: Circulating tumour cells (CTCs) represent a morphologically distinct subset of cancer cells, which aid the metastatic spread. The ExPeCT trial aimed to examine the effectiveness of a structured exercise programme in modulating levels of CTCs and platelet cloaking in patients with metastatic prostate cancer. METHODS: Participants (n = 61) were randomised into either standard care (control) or exercise arms. Whole blood was collected for all participants at baseline (T0), three months (T3) and six months (T6), and analysed for the presence of CTCs, CTC clusters and platelet cloaking. CTC data was correlated with clinico-pathological information. RESULTS: Changes in CTC number were observed within group over time, however no significant difference in CTC number was observed between groups over time. Platelet cloaking was identified in 29.5% of participants. A positive correlation between CTC number and white cell count (WCC) was observed (p = 0.0001), in addition to a positive relationship between CTC clusters and PSA levels (p = 0.0393). CONCLUSION: The presence of platelet cloaking has been observed in this patient population for the first time, in addition to a significant correlation between CTC number and WCC. TRIAL REGISTRATION: ClincalTrials.gov identifier NCT02453139.


Assuntos
Biomarcadores Tumorais/sangue , Plaquetas/metabolismo , Células Neoplásicas Circulantes/metabolismo , Neoplasias da Próstata/sangue , Idoso , Plaquetas/patologia , Contagem de Células , Humanos , Masculino , Metástase Neoplásica , Células Neoplásicas Circulantes/patologia , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia
14.
Int J Mol Sci ; 21(24)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33348918

RESUMO

Despite outstanding advances in diagnosis and the treatment of primary uveal melanoma (UM), nearly 50% of UM patients develop metastases via hematogenous dissemination, driven by the epithelial-mesenchymal transition (EMT). Despite the failure in UM to date, a liquid biopsy may offer a feasible non-invasive approach for monitoring metastatic disease progression and addressing protracted dormancy. To detect circulating tumor cells (CTCs) in UM patients, we evaluated the mRNA expression of EMT-associated transcription factors in CD45-depleted blood fraction, using qRT-PCR. ddPCR was employed to assess UM-specific GNA11, GNAQ, PLCß4, and CYSLTR2 mutations in plasma DNA. Moreover, microarray analysis was performed on total RNA isolated from tumor tissues to estimate the prognostic value of EMT-associated gene expression. In total, 42 primary UM and 11 metastatic patients were enrolled. All CD45-depleted samples were negative for CTC when compared to the peripheral blood fraction of 60 healthy controls. Tumor-specific mutations were detected in the plasma of 21.4% patients, merely, in 9.4% of primary UM, while 54.5% in metastatic patients. Unsupervised hierarchical clustering of differentially expressed EMT genes showed significant differences between monosomy 3 and disomy 3 tumors. Newly identified genes can serve as non-invasive prognostic biomarkers that can support therapeutic decisions.


Assuntos
Biomarcadores Tumorais/genética , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Melanoma/genética , Células Neoplásicas Circulantes/patologia , Neoplasias Uveais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Deleção Cromossômica , Cromossomos Humanos Par 3/genética , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Feminino , Seguimentos , Humanos , Biópsia Líquida , Masculino , Melanoma/secundário , Melanoma/terapia , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/metabolismo , Prognóstico , Neoplasias Uveais/secundário , Neoplasias Uveais/terapia
15.
Int J Mol Sci ; 21(24)2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339353

RESUMO

Circulating tumor cells (CTCs) are a rare tumor cell subpopulation induced and selected by the tumor microenvironment's extreme conditions. Under hypoxia and starvation, these aggressive and invasive cells are able to invade the lymphatic and circulatory systems. Escaping from the primary tumor, CTCs enter into the bloodstream to form metastatic deposits or re-establish themselves in cancer's primary site. Although radiotherapy is widely used to cure solid malignancies, it can promote metastasis. Radiation can disrupt the primary tumor vasculature, increasing the dissemination of CTCs. Radiation also induces epithelial-mesenchymal transition (EMT) and eliminates suppressive signaling, causing the proliferation of existent, but previously dormant, disseminated tumor cells (DTCs). In this review, we collect the results and evidence underlying the molecular mechanisms of CTCs and DTCs and the effects of radiation and hypoxia in developing these cells.


Assuntos
Neoplasias/metabolismo , Células Neoplásicas Circulantes/metabolismo , Hipóxia Tumoral , Animais , Humanos , Invasividade Neoplásica , Neoplasias/patologia , Células Neoplásicas Circulantes/efeitos da radiação , Tolerância a Radiação
16.
Int J Mol Sci ; 21(24)2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33322643

RESUMO

Breast cancer is the most common cancer among women worldwide. Although the five-, ten- and fifteen-year survival rates are good for breast cancer patients diagnosed with early-stage disease, some cancers recur many years after completion of primary therapy. Tumor heterogeneity and clonal evolution may lead to distant metastasis and therapy resistance, which are the main causes of breast cancer-associated deaths. In the clinic today, imaging techniques like mammography and tissue biopsies are used to diagnose breast cancer. Even though these methods are important in primary diagnosis, they have limitations when it comes to longitudinal monitoring of residual disease after treatment, disease progression, therapy responses, and disease recurrence. Over the last few years, there has been an increasing interest in the diagnostic, prognostic, and predictive potential of circulating cancer-derived material acquired through liquid biopsies in breast cancer. Thanks to the development of sensitive devices and platforms, a variety of tumor-derived material, including circulating cancer cells (CTCs), circulating DNA (ctDNA), and biomolecules encapsulated in extracellular vesicles, can now be extracted and analyzed from body fluids. Here we will review the most recent studies on breast cancer, demonstrating the clinical potential and utility of CTCs and ctDNA. We will also review literature illustrating the potential of circulating exosomal RNA and proteins as future biomarkers in breast cancer. Finally, we will discuss some of the advantages and limitations of liquid biopsies and the future perspectives of this field in breast cancer management.


Assuntos
Neoplasias da Mama/metabolismo , Células Neoplásicas Circulantes/metabolismo , Neoplasias da Mama/patologia , Exossomos/metabolismo , Humanos , Células Neoplásicas Circulantes/patologia , Prognóstico
17.
Medicine (Baltimore) ; 99(40): e22242, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019399

RESUMO

BACKGROUND: To evaluate the clinical value of circulating tumor cell (CTC) detection in peripheral blood for the diagnosis and prognosis of hepatocellular carcinoma (HCC). METHODS: Public databases were searched, and a meta-analysis was performed to determine the specificity, sensitivity, negative- likelihood ratio (NLR) and positive-likelihood ratio (PLR), and diagnostic odds ratio (dOR) of CTC detection for the diagnosis of HCC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed for the association of CTC detection with overall survival (OS) and HCC recurrence. The Meta-DiSc 1.4 and Review Manager 5.2 software programs were used for statistical analysis. RESULTS: Meta-analysis of 20 studies including 1191 patients showed that the specificity, sensitivity, NLR, PLR, and dOR of CTC testing for HCC diagnosis were 0.60 (95% CI = 0.57-0.63), 0.95 (95%CI = 0.93-0.96), 0.36 (95%CI = 0.28-0.48), 11.64 (95%CI = 5.85-23.14), and 38.94 (95%CI = 18.33-82.75), respectively. Meta-analysis of 18 studies including 1466 patients indicated that the OS of CTC-positive HCC patients was less than that of CTC-negative patients (HR = 2.31; 95% CI = 1.55-3.42; P < .01). Meta-analysis of 5 studies including 339 patients revealed that the presence of CTCs in peripheral blood significantly increased the risk of HCC recurrence (HR = 3.03, 95% CI = 1.89-4.86; P < .01). CONCLUSION: CTCs in peripheral blood may be a useful marker for HCC diagnosis. In addition, the prognosis of CTC-positive HCC patients was significantly worse than that of CTC-negative HCC patients. Therefore, further studies are warranted to confirm the clinical potential of CTC detection in peripheral blood in patients with primary HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Células Neoplásicas Circulantes/metabolismo , Biomarcadores Tumorais , Carcinoma Hepatocelular/sangue , Contagem de Células , Humanos , Neoplasias Hepáticas/sangue , Recidiva Local de Neoplasia , Células Neoplásicas Circulantes/patologia , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Sensibilidade e Especificidade , Análise de Sobrevida
18.
Anticancer Res ; 40(10): 5577-5582, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988881

RESUMO

BACKGROUND/AIM: Clusters of circulating tumor cells (CTCs) increase metastatic potential compared to single CTC. However, conventional technologies have been unable to generate an accurate analysis of single and cluster CTCs in the peripheral blood. We propose an effective strategy to detect and isolate both single and cluster CTCs using two size-selective microfilters. MATERIALS AND METHODS: Five ml of whole blood were collected from 10 patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer. Single and cluster CTCs were identified using precision microfiltration membranes with two distinct pore sizes together with anti-EpCAM antibody labeling. RESULTS: Single and cluster CTCs were detected by simultaneously using two size-selective microfilters. The EGFR-L858R mutation was detected in the DNA from cells captured using both microfilters. CONCLUSION: Our method can be used to detect and isolate single and cluster CTCs in the whole blood and may facilitate the development of a liquid biopsy strategy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , DNA Tumoral Circulante/sangue , Molécula de Adesão da Célula Epitelial/sangue , Células Neoplásicas Circulantes/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Separação Celular , Feminino , Humanos , Biópsia Líquida , Masculino , Pessoa de Meia-Idade , Mutação/genética , Células Neoplásicas Circulantes/patologia
19.
Anticancer Res ; 40(10): 5679-5685, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988893

RESUMO

BACKGROUND/AIM: The presence of circulating tumor cells (CTC) has been reported to have an impact on prognosis in different tumor entities. Little is known about CTC morphology and heterogeneity. PATIENTS AND METHODS: In a multicenter setting, pre-therapeutic peripheral blood specimens were drawn from patients with non-metastatic esophageal adenocarcinoma (EAC). CTCs were captured by size-based filtration (ScreenCell®), subsequently Giemsa-stained and evaluated by two trained readers. The isolated cells were categorized in groups based on morphologic criteria. RESULTS: Small and large single CTCs, as well as CTC-clusters, were observed in 69.2% (n=81) of the 117 specimens; small CTCs were observed most frequently (59%; n=69), followed by large CTCs (40%; n=47) and circulating cancer-associated macrophage-like cells (CAMLs; 34.2%, n=40). Clusters were rather rare (12%; n=14). CTC/CAML were heterogeneous in the cohort, but also within one specimen. Neither the presence of the CTC subtypes/CAMLs nor the exact cell count were associated with the primary clinical TNM stage. CONCLUSION: Morphologically heterogenic CTCs and CAMLs are present in patients with non-metastatic, non-pretreated EAC.


Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Neoplasias Esofágicas/sangue , Células Neoplásicas Circulantes/metabolismo , Adenocarcinoma/patologia , Contagem de Células , Separação Celular , Neoplasias Esofágicas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/patologia , Prognóstico
20.
Anticancer Res ; 40(10): 5837-5844, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988913

RESUMO

BACKGROUND/AIM: Renal cell carcinoma (RCC) is one of the most common malignancies of the urinary tract. Venous migration, tumor thrombus and metastases are often seen in patients with RCC and are adverse prognostic factors. Intravascular tumor growth along the renal vein into the inferior vena cava occurs in up to 10% of all patients with RCC. Furthermore, extension of the tumor reaching the right atrium is detected in approximately 1% of all patients. Synchronous involvement of pulmonary arteries with tumor emboli is very rare and challenging. Management of metastatic RCC includes surgical resection of renal and metastatic lesions. We present 3 cases of patients with RCC tumor thrombus extending into the inferior vena cava (IVC) and with pulmonary emboli of the tumor thrombus into one of the branches of the main pulmonary artery. All the cases had simultaneous resection of the kidney tumor with the tumor thrombus and pulmonary lobectomy that included the tumor emboli with satisfactory outcome. CASE REPORT: We present a series of cases of RCC with tumor extension into the inferior vena cava (IVC) and with tumor emboli to the pulmonary arteries. Surgical procedure in all cases consisted of radical nephrectomy with IVC tumor thrombus resection, along with a thoracotomy with lung resection including the tumor emboli to one of the branches of the main pulmonary artery. Synchronous metastatic lesions were found on the liver in one case and contiguous extension of renal tumor to the pancreas in another. CONCLUSION: In patients with IVC thrombus with synchronous pulmonary artery tumor embolus, such as the cases presented in this series, a careful multidisciplinary management approach is preferable. Transplant technique used in our open approach minimizes complications, blood loss, and provides excellent visualization for abdominal vascular manipulation of IVC. This provides a potentially curable treatment option with acceptable survival rates.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Pulmonares/cirurgia , Artéria Pulmonar/cirurgia , Veia Cava Inferior/cirurgia , Adulto , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Rim/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Metástase Neoplásica , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Nefrectomia/métodos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/patologia , Veias Renais/diagnóstico por imagem , Veias Renais/patologia , Veias Renais/cirurgia , Trombose/diagnóstico por imagem , Trombose/patologia , Trombose/cirurgia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/patologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/patologia , Trombose Venosa/cirurgia
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