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1.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800799

RESUMO

Liquid biopsies constitute a minimally invasive means of managing cancer patients, entailing early diagnosis, follow-up and prediction of response to therapy. Their use in the germ cell tumor field is invaluable since diagnostic tissue biopsies (which are invasive) are often not performed, and therefore only a presumptive diagnosis can be made, confirmed upon examination of the surgical specimen. Herein, we provide an overall review of the current liquid biopsy-based biomarkers of this disease, including the classical, routinely used serum tumor markers-the promising microRNAs rapidly approaching the introduction into clinical practice-but also cell-free DNA markers (including DNA methylation) and circulating tumor cells. Finally, and importantly, we also explore novel strategies and challenges for liquid biopsy markers and methodologies, providing a critical view of the future directions for liquid biopsy tests in this field, highlighting gaps and unanswered questions.


Assuntos
Biópsia Líquida , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Procedimentos Clínicos , DNA de Neoplasias/química , Gerenciamento Clínico , Feminino , Humanos , Masculino , MicroRNAs/análise , Proteínas de Neoplasias/análise , Neoplasias Embrionárias de Células Germinativas/sangue , Neoplasias Embrionárias de Células Germinativas/química , Neoplasias Embrionárias de Células Germinativas/patologia , Células Neoplásicas Circulantes , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/química , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , RNA Neoplásico/análise , Neoplasias Testiculares/sangue , Neoplasias Testiculares/química , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patologia
2.
Adv Exp Med Biol ; 1286: 125-134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33725350

RESUMO

Circulating tumor cells (CTCs) are malignant cells separate from primary tumors, which can migrate through the peripheral blood, colonize other tissues, and lead to the formation of metastases. The first description of CTCs dates back to 1869 when Thomas Ashworth recognized malignant cells similar to the ones of the primary tumor in the blood vessels of an autopsied patient with metastatic cancer. Currently, CTCs have been identified in various types of cancer and have been recognized for their clinical value in the prediction of prognosis, diagnosis of minimal residual diseases, assessment of tumor sensitivity to anticancer drugs, and personalization of therapies. However, research about these topics has several limitations, principally the rarity of CTCs in bloodstream and their heterogeneous characteristics, which makes detection and isolation difficult. As a result of these limitations, current studies are focused on improvement of isolation and characterization techniques to achieve better sensitivity in clinical applications. This review covers the methods of CTC isolation and detection and current research progression on CTC in different cancer types. The clinical applications, limitations, and perspectives of CTCs are also discussed.


Assuntos
Antineoplásicos , Células Neoplásicas Circulantes , Biomarcadores Tumorais , Contagem de Células , Humanos , Metástase Neoplásica , Células Neoplásicas Circulantes/patologia
3.
Methods Mol Biol ; 2265: 277-286, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704722

RESUMO

Molecular testing of tumor biopsies allows for the identification of the key mutations driving a patient's cancer. However, this is limited to singular nodes and may not accurately reflect cancer heterogeneity. Circulating tumor cell (CTC) analyses offer a noninvasive method of interrogating the genomic profile of patient-derived tumor material. To date, molecular analysis of CTCs has relied on the characterization of bulk or pooled CTC lysates, limiting the detection of minor tumorigenic CTC subclones. Here, we show a workflow enabling BRAFV600E/NRASQ61R mutation detection from single cultured melanoma cells by combining micromanipulation and genomic material amplification methods. This workflow can be directly integrated into circulating tumor cell analysis applications.


Assuntos
GTP Fosfo-Hidrolases/genética , Melanoma/genética , Proteínas de Membrana/genética , Mutação de Sentido Incorreto , Células Neoplásicas Circulantes , Proteínas Proto-Oncogênicas B-raf/genética , Análise de Célula Única , Substituição de Aminoácidos , Linhagem Celular Tumoral , Humanos , Melanoma/patologia
4.
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
5.
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
6.
Methods Mol Biol ; 2265: 203-212, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704716

RESUMO

Early detection of cancer has been a goal of cancer research in general and melanoma research in particular (Birnbaum et al., Lancet Glob Health 6:e885-e893, 2018; Alendar et al., Bosnian J Basic Med Sci 9:77-80, 2009). Early detection of metastasis has been targeted as pivotal to increasing survival rates (Menezes et al., Adv Cancer Res 132:1-44, 2016). Melanoma, though curable in its early stages, has a dramatic decrease in survival rates once metastasis has occurred (Sharma et al., Biotechnol Adv 36:1063-1078, 2018). The transition to metastasis is not well understood and is an area of increasing interest. Metastasis is always premeditated by the shedding of circulating tumor cells (CTCs) from the primary tumor. The ability to isolate rare CTCs from the bloodstream has led to a host of new targets and therapies for cancer (Micalizzi et al., Genes Dev 31:1827-1840, 2017). Detection of CTCs also allows for disease progression to be tracked in real time while eliminating the need to wait for additional tumors to grow. Using a photoacoustic flowmeter, in which we induce ultrasonic responses from circulating melanoma cells (CMCs), we identify and quantify these cells in order to track disease progression. Additionally, these CMCs are captured and isolated allowing for future analysis such as RNA-Seq or microarray analysis.


Assuntos
Citometria de Fluxo/métodos , Melanoma/diagnóstico , Células Neoplásicas Circulantes , Técnicas Fotoacústicas/instrumentação , Técnicas Fotoacústicas/métodos , Reologia/instrumentação , Reologia/métodos , Neoplasias Cutâneas/diagnóstico , Progressão da Doença , Detecção Precoce de Câncer/métodos , Citometria de Fluxo/instrumentação , Biblioteca Gênica , Humanos , Imuno-Histoquímica/métodos , Melanoma/sangue , Melanoma/genética , Melanoma/patologia , Metástase Neoplásica/diagnóstico , Metástase Neoplásica/patologia , Células Neoplásicas Circulantes/patologia , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Ultrassonografia/métodos
7.
Methods Mol Biol ; 2265: 213-222, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704717

RESUMO

Within the last decade, circulating tumor cells (CTCs) have emerged as a promising biomarker for prognostication, treatment monitoring, and detection of markers of treatment resistance, and their isolation can be used as a minimally invasive means of profiling tumors across multiple body sites. However, CTCs represent a minuscule fraction of the total circulating cells in a patient. Therefore, sensitive isolation methods are needed for the detection and downstream analysis of these cells. Herein we describe a sensitive method for melanoma CTC isolation using a multi-marker immunomagnetic bead method. This method has been purposely optimized to detect CTCs in melanoma patients.


Assuntos
Antígenos de Neoplasias/imunologia , Separação Imunomagnética/métodos , Leucócitos Mononucleares/metabolismo , Melanoma/sangue , Antineoplásicos Imunológicos/imunologia , Biomarcadores Tumorais/metabolismo , Técnicas de Cultura de Células/métodos , Linhagem Celular Tumoral , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Melanoma/metabolismo , Melanoma/patologia , Células Neoplásicas Circulantes
8.
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
9.
Methods Mol Biol ; 2265: 223-233, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704718

RESUMO

The advent of personalized medicines targeting cell signaling pathways has radically improved melanoma patient outcomes. More recently, immune-modulating therapies disrupting the PD-1/PD-L1 axis have become a powerful tool in the treatment of a range of melanoma, showing a profound improvement in the overall survival outcomes. However, immune checkpoint inhibitors (ICIs) are associated with considerable toxicities and appear to only be efficacious in a subset of melanoma patients. Therefore, there is an urgent need to identify biomarkers that can determine if patients will or will not respond to ICI therapy. Here, we describe an optimized method for analyzing PD-L1 expression on circulating melanoma cells following immunomagnetic enrichment from patient blood samples.


Assuntos
Antígeno B7-H1/metabolismo , Separação Imunomagnética/métodos , Melanoma/sangue , Células Neoplásicas Circulantes/imunologia , Anticorpos/imunologia , Antígeno B7-H1/imunologia , Humanos , Leucócitos Mononucleares/citologia , Biópsia Líquida/métodos , Melanoma/diagnóstico
10.
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
12.
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
13.
Ann Oncol ; 32(4): 466-477, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33548389

RESUMO

Liquid biopsy in cancer has gained momentum in clinical research and is experiencing a boom for a variety of applications. There are significant efforts to utilize liquid biopsies in cancer for early detection and treatment stratification, as well as residual disease and recurrence monitoring. Although most efforts have used circulating tumor cells and circulating tumor DNA for this purpose, exosomes and other extracellular vesicles have emerged as a platform with potentially broader and complementary applications. Exosomes/extracellular vesicles are small vesicles released by cells, including cancer cells, into the surrounding biofluids. These exosomes contain tumor-derived materials such as DNA, RNA, protein, lipid, sugar structures, and metabolites. In addition, exosomes carry molecules on their surface that provides clues regarding their origin, making it possible to sort vesicle types and enrich signatures from tissue-specific origins. Exosomes are part of the intercellular communication system and cancer cells frequently use them as biological messengers to benefit their growth. Since exosomes are part of the disease process, they have become of tremendous interest in biomarker research. Exosomes are remarkably stable in biofluids, such as plasma and urine, and can be isolated for clinical evaluation even in the early stages of the disease. Exosome-based biomarkers have quickly become adopted in the clinical arena and the first exosome RNA-based prostate cancer test has already helped >50 000 patients in their decision process and is now included in the National Comprehensive Cancer Network guidelines for early prostate cancer detection. This review will discuss the advantages and challenges of exosome-based liquid biopsies for tumor biomarkers and clinical implementation in the context of circulating tumor DNA and circulating tumor cells.


Assuntos
DNA Tumoral Circulante , Exossomos , Células Neoplásicas Circulantes , Biomarcadores Tumorais , Humanos , Biópsia Líquida , Masculino , Recidiva Local de Neoplasia
14.
J Vis Exp ; (167)2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33586709

RESUMO

Leptomeningeal disease (LMD) is an uncommon type of central nervous system (CNS) metastasis to the cerebral spinal fluid (CSF). The most common cancers that cause LMD are breast and lung cancers and melanoma. Patients diagnosed with LMD have a very poor prognosis and generally survive for only a few weeks or months. One possible reason for the lack of efficacy of systemic therapy against LMD is the failure to achieve therapeutically effective concentrations of drug in the CSF because of an intact and relatively impermeable blood-brain barrier (BBB) or blood-CSF barrier across the choroid plexus. Therefore, directly administering drugs intrathecally or intraventricularly may overcome these barriers. This group has developed a model that allows for the effective delivery of therapeutics (i.e., drugs, antibodies, and cellular therapies) chronically and the repeated sampling of CSF to determine drug concentrations and target modulation in the CSF (when the tumor microenvironment is targeted in mice). The model is the murine equivalent of a magnetic resonance imaging-compatible Ommaya reservoir, which is used clinically. This model, which is affixed to the skull, has been designated as the "Murine Ommaya." As a therapeutic proof of concept, human epidermal growth factor receptor 2 antibodies (clone 7.16.4) were delivered into the CSF via the Murine Ommaya to treat mice with LMD from human epidermal growth factor receptor 2-positive breast cancer. The Murine Ommaya increases the efficiency of drug delivery using a miniature access port and prevents the wastage of excess drug; it does not interfere with CSF sampling for molecular and immunological studies. The Murine Ommaya is useful for testing novel therapeutics in experimental models of LMD.


Assuntos
Doenças do Sistema Nervoso Central/terapia , Sistemas de Liberação de Medicamentos , Xenoenxertos/fisiologia , Modelos Biológicos , Animais , Neoplasias da Mama/patologia , Feminino , Injeções Intraventriculares , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/patologia , Camundongos , Metástase Neoplásica , Células Neoplásicas Circulantes/patologia , Prognóstico
15.
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
16.
J Biomech ; 117: 110235, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33486262

RESUMO

Microfluidic devices can be thought of as comprising interconnected miniaturized compartments performing multiple experimental tasks individually or in parallel in an integrated fashion. Due to its small size, portability, and low cost, attempts have been made to incorporate detection assays into microfluidic platforms for diseases such as cancer and infection. Some of these technologies have served as point-of-care and sample-to-answer devices. The methods for detecting biomarkers in different diseases usually share similar principles and can conveniently be adapted to cope with arising health challenges. The COVID-19 pandemic is one such challenge that is testing the performance of both our conventional and newly-developed disease diagnostic technologies. In this mini-review, we will first look at the progress made in the past few years in applying microfluidics for liquid biopsy and infectious disease detection. Following that, we will use the current pandemic as an example to discuss how such technological advancements can help in the current health challenge and better prepare us for future ones.


Assuntos
/diagnóstico , Biópsia Líquida/métodos , Microfluídica/métodos , Testes Imediatos , Biomarcadores , DNA Tumoral Circulante , Exossomos , Humanos , Dispositivos Lab-On-A-Chip , Aprendizado de Máquina , Neoplasias/diagnóstico , Células Neoplásicas Circulantes
17.
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
18.
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
19.
AJR Am J Roentgenol ; 216(3): 769-775, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33405948

RESUMO

OBJECTIVE. Pulmonary intravascular metastasis is a special type of pulmonary metastasis of malignancies; however, few relevant studies have been performed. This study aimed to determine the characteristics of pulmonary intravascular metastasis and improve understanding of the disease by retrospective analysis of FDG PET/CT and thin-layer high-resolution CT (HRCT) imaging of the chest in patients with tumors. MATERIALS AND METHODS. We identified all patients who underwent FDG PET/CT at two hospitals between January 2016 and February 2019 and conducted a comparative analysis of HRCT and PET/CT images. In total, 84 patients (38 women and 46 men) ranging in age from 35 to 82 years old (mean age, 54.7 ± 14.5 [SD] years) participated in the study. Patient characteristics were summarized, and diagnosis was confirmed by chest CT or PET/CT follow-up. RESULTS. A total of 260 pulmonary intravascular metastases were found, which were classified as type I (no significant abnormality, n = 5), type II (abrupt and uneven thickening of the pulmonary vessel, n = 118), type III (simultaneous invasion of adjacent pulmonary vessel, n = 121), and type IV (large strip-shaped high-density mass, n = 16). The majority were located in peripheral pulmonary vessels (94.2% [245/260]). FDG up-take was increased in 252 lesions, and the mean SUVmax was 4.6 ± 2.5. CONCLUSION. The combination of PET/CT and chest HRCT is an effective approach for detecting pulmonary intravascular metastasis. The linear pattern of FDG uptake, abnormal pulmonary blood vessel morphology, and location (below the lung segment) are specific indicators for the diagnosis of pulmonary intravascular metastasis and should be recognized by clinicians and radiologists.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Tomografia Computadorizada Multidetectores/métodos , Células Neoplásicas Circulantes , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Pulmão/irrigação sanguínea , Pulmão/diagnóstico por imagem , Pulmão/metabolismo , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/metabolismo , Radiografia Torácica/métodos , Compostos Radiofarmacêuticos/farmacocinética , Estudos Retrospectivos
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