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1.
Crit Rev Oncol Hematol ; 146: 102879, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32005411

RESUMEN

Cell-free circulating tumor DNA (ct-DNA) reflecting the whole tumor spatial and temporal heterogeneity currently represents the most promising candidate for liquid biopsy strategy in glioma. Unlike other solid tumors, it is now widely accepted that the best source of ct-DNA for glioma patients is the cerebrospinal fluid, since blood levels are usually low and detectable only in few cases. A cerebrospinal fluid ct-DNA liquid biopsy approach may virtually support all the stages of glioma management, from facilitating molecular diagnosis when surgery is not feasible, to monitoring tumor response, identifying early recurrence, tracking longitudinal genomic evolution, providing a new molecular characterization at recurrence and allowing patient selection for targeted therapies. This review traces the history of ct-DNA liquid biopsy in the field of diffuse malignant gliomas, describes its current status and analyzes what are the future perspectives and pitfalls of this potentially revolutionary molecular tool.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/líquido cefalorraquídeo , ADN Tumoral Circulante/líquido cefalorraquídeo , ADN de Neoplasias/metabolismo , Glioma/líquido cefalorraquídeo , Biopsia Líquida/métodos , Células Neoplásicas Circulantes/metabolismo , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , ADN de Neoplasias/genética , Genes Relacionados con las Neoplasias/genética , Glioblastoma/líquido cefalorraquídeo , Glioblastoma/genética , Glioblastoma/patología , Glioma/genética , Glioma/patología , Humanos , Mutación , Clasificación del Tumor , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/metabolismo , Células Neoplásicas Circulantes/patología
2.
Medicine (Baltimore) ; 99(8): e19097, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32080083

RESUMEN

Liquid biopsy is an emerging technique for noninvasive detection of various cancers. Majority of liquid biopsy tests still, however, use solitary type of biomarkers with unsatisfactory sensitivity and specificity. To this end, a combined approach of circulating tumor cells (CTCs) and salivary mRNA biomarkers was evaluated for discriminating non-small-cell lung cancer (NSCLC) from healthy controls.Our study included a discovery phase to find multiple biomarkers, and an independent validation phase to confirm the applicability of the selected biomarkers. In the discovery phase, CTC level in blood and 5 mRNA biomarkers in saliva (i.e., CCNI, Epidermal growth factor receptor [EGFR], FGF19, FRS2, and GREB1) were measured for 140 NSCLC patients and 140 healthy controls, followed by developing a predictive model. Next, this panel of biomarkers was applied to another patient cohort consisted of 60 patients with NSCLC and 60 healthy controls in the validation phase.We found that our novel biomarker panel could differentiate patients with NSCLC from healthy controls with high sensitivity (92.1%) and high specificity (92.9%) in the discovery phase. In the validation phase, we achieved sensitivity of 88.3% and specificity of 90.0%.To our best knowledge, it is the first time that a combined use of CTC and salivary mRNA biomarkers were applied for noninvasive detection of NSCLC.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Células Neoplásicas Circulantes/metabolismo , ARN Mensajero/metabolismo , Saliva/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Ciclina I/metabolismo , Receptores ErbB/metabolismo , Femenino , Factores de Crecimiento de Fibroblastos/metabolismo , Humanos , Biopsia Líquida/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Células Neoplásicas Circulantes/patología , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad
3.
Adv Exp Med Biol ; 1225: 19-29, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32030645

RESUMEN

In the past, cancer development was studied in terms of genetic mutations acquired in cancer cells at each stage of the development. We present an emerging model for cancer development in which the tumor microenvironment (TME) plays an integral part. In this model, the tumor development is initiated by a slowly growing nearly homogeneous colony of cancer cells that can evade detection by the cell's innate mechanism of immunity such as natural killer (NK) cells (first stage; colonization). Subsequently, the colony develops into a tumor filled with lymphocytes and stromal cells, releasing pro-inflammatory cytokines, growth factors, and chemokines (second stage; lymphocyte infiltration). Cancer progression proceeds to a well-vesiculated silent tumor releasing no inflammatory signal, being nearly devoid of lymphocytes (third stage; silenced). Eventually some cancer cells within a tumor undertake epithelial-to-mesenchymal transition (EMT), which leads to cancer metastasis (fourth stage; EMT). If a circulating metastasized cancer cell finds a niche in a new tissue and evades detection by NK cells, it can establish a new colony in which very few stromal cells are present (fifth stage; metastasis), which is much like a colony at the first stage of development. At every stage, cancer cells influence their own TME, and in turn, the TME influences the cancer cells contained within, either by direct interaction between cancer cells and stromal cells or through exchange of cytokines. In this article, we examine clinical findings and animal experiments pertaining to this paradigm-shifting model and consider if, indeed, some aspects of cancer development are governed solely by the TME.


Asunto(s)
Carcinogénesis , Neoplasias/patología , Microambiente Tumoral , Animales , Carcinogénesis/inmunología , Carcinogénesis/patología , Transición Epitelial-Mesenquimal , Humanos , Células Asesinas Naturales/inmunología , Neoplasias/inmunología , Células Neoplásicas Circulantes/inmunología , Células Neoplásicas Circulantes/patología , Células del Estroma/inmunología , Células del Estroma/patología
4.
Recent Results Cancer Res ; 215: 3-24, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31605221

RESUMEN

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.


Asunto(s)
Metástasis de la Neoplasia/genética , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Progresión de la Enfermedad , Humanos , Mutación
5.
Recent Results Cancer Res ; 215: 89-104, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31605225

RESUMEN

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.


Asunto(s)
Biología Computacional , Neoplasias/patología , Células Neoplásicas Circulantes/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Ensayos Analíticos de Alto Rendimiento , Humanos , Neoplasias/diagnóstico , Neoplasias/terapia , Células Neoplásicas Circulantes/patología , Análisis de la Célula Individual
6.
Recent Results Cancer Res ; 215: 105-125, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31605226

RESUMEN

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.


Asunto(s)
Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Células Neoplásicas Circulantes/metabolismo , Biomarcadores de Tumor/análisis , Humanos , Células Neoplásicas Circulantes/patología
7.
Recent Results Cancer Res ; 215: 127-145, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31605227

RESUMEN

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.


Asunto(s)
Neoplasias de la Mama/patología , Células Neoplásicas Circulantes/metabolismo , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Progresión de la Enfermedad , Humanos , Células Neoplásicas Circulantes/patología , Medicina de Precisión , Pronóstico
8.
Recent Results Cancer Res ; 215: 147-160, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31605228

RESUMEN

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.


Asunto(s)
Neoplasias de la Mama/patología , Metástasis de la Neoplasia/patología , Células Neoplásicas Circulantes/patología , Humanos
10.
Talanta ; 207: 120261, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31594567

RESUMEN

Significant progress on circulating tumor cells (CTCs) has profound impact for noninvasive tumor profiling including early diagnosis, treatment monitoring, and metastasis recognition. Therefore, CTCs based liquid biopsy technology is taking a rapid growth in the field of precision oncology. The label-free approaches relied on microfluidic chip stand out from a crowd of methods that suffer from time consuming, extensive blood samples, lost target cells and labor-intensive operation. In this paper, a label-free separation microfluidic device was developed using multistage channel, which took full advantage of inertial lift force. Our strategy demonstrated CTCs were efficiently isolated from untreated human blood samples including antibody conjugation and erythrocyte lysis. This device was applied for isolating human brain malignant glioma cells that were spiked in human peripheral blood samples. The experimental condition was optimized and exhibited an average separation efficiency of ≥ 90% across cell morphological analysis, up to 84.96% purity of collected CTCs and the viability of all cells is >95%, which was better than other one-step CTCs separation methods. Furthermore, the CTCs were successfully separated from untreated clinical blood sample of cancer patient on the proposed microfluidic device. The entire experimental procedures are extremely low-cost and easy manipulation. It is believed that the proposed multistage microfluidic chip can become a promising tool for CTCs separation and early diagnosis of cancer.


Asunto(s)
Separación Celular/instrumentación , Hidrodinámica , Dispositivos Laboratorio en un Chip , Células Neoplásicas Circulantes/patología , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Diseño de Equipo , Eritrocitos/patología , Glioma/patología , Humanos
11.
Anticancer Res ; 39(12): 6829-6834, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31810949

RESUMEN

BACKGROUND/AIM: Circulating tumor cells (CTCs) are tumor cells shed from tumor sites and circulate in the peripheral blood. CTCs can be a surrogate biomarker of recurrence and prognosis. Because surgical manipulation could promote CTCs, it is important to reduce CTCs during surgery. This study aimed to evaluate the effectiveness of intraoperative wedge resection of the tumor site before lobectomy. PATIENTS AND METHODS: A total of 297 resected stage I lung adenocarcinoma patients were retrospectively reviewed. Patients were divided into two groups: Wedge and Non-Wedge. Recurrence-free survival (RFS) curves were plotted using the Kaplan-Meier method. Cox regression analyses were used to evaluate the hazard ratio (HR) with the endpoint RFS. RESULTS: The 5-year RFS rates were 92.9% and 85.5%, in Wedge and Non-Wedge groups, respectively (p=0.006). Wedge resection was an independent factor associated with RFS (HR=0.342, 95%CI=0.141-0.830, p=0.018). CONCLUSION: Wedge resection before lobectomy for lung adenocarcinoma patients can improve RFS rates.


Asunto(s)
Adenocarcinoma del Pulmón/cirugía , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Venas Pulmonares/cirugía , Adenocarcinoma del Pulmón/irrigación sanguínea , Adenocarcinoma del Pulmón/patología , Femenino , Humanos , Periodo Intraoperatorio , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Células Neoplásicas Circulantes/patología , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Cirugía Torácica Asistida por Video , Resultado del Tratamiento
12.
Ann Hematol ; 98(12): 2769-2780, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31748925

RESUMEN

Difficulty in regularly analyzing marrow myeloma cells (MMCs) and low frequency of circulating myeloma cells (CMCs) in blood presents challenges for monitoring minimal residual disease (MRD) in multiple myeloma (MM). We have developed a set of method for enrichment of CMCs by immunomagetic beads (IMB) combined with flow cytometry (IMB-FCM) based on CD38-APC/CD138-APC antibodies in U266-spiked samples and in 122 patient samples. U266 cell capture efficiency of CD38/CD138-IMB-FCM (6.960, 2.574) was 6- and 2-fold higher than that of FCM (1.032), and the sensitivity of FCM and IMB-FCM was 0.01% and 0.001%, respectively. In MM cohort, the positive rate of CMCs by IMB-FCM increased from 60.5~70.0 to 85~87.2% in newly diagnosed/relapsed and partial remission (PR) patients compared with by FCM (P < 0.05). Two complete remission (CR) patients contain certain amounts of CMCs by IMB-FCM while no CMCs and MMCs were detectable by FCM. Patients exhibiting PR and CR upon therapy had much lower CMC and MMC counts than newly diagnosed/relapsed patients (P < 0.005). Based on MRD measurement in BM and PB samples, all FCM-negative BM samples were also paired with FCM/IMB-FCM-negative PB samples among newly diagnosed, relapsed, and PR patients, and FCM-positive BM samples were accompanied by IMB-FCM-positive results in 88% of corresponding PB samples. CMCs strongly associated with other clinical biomarkers of disease burden, including elevated MMCs, ß2-MG, sCrea, and DS and ISS stages, and more serious anemia, bone destruction, and renal impairment (P < 0.05). Logistic regression analysis revealed that elevated ß2-MG and moderate-to-more anemia were significant risk factors for the presence of CMCs (P < 0.05). As a noninvasive "liquid biopsy" of monitoring MRD, the potential of IMB-FCM for CMC detection may complement or minimize bone marrow aspiration in future treatment of MM patients.


Asunto(s)
Citometría de Flujo , Separación Inmunomagnética , Mieloma Múltiple/sangre , Células Neoplásicas Circulantes/metabolismo , Adulto , Línea Celular Tumoral , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Mieloma Múltiple/terapia , Neoplasia Residual , Células Neoplásicas Circulantes/patología
14.
Nat Med ; 25(10): 1534-1539, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31591595

RESUMEN

Approximately 50% of patients with early-stage non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years1,2. Detection of circulating tumor cells (CTCs) at the time of surgery may represent a tool to identify patients at higher risk of recurrence for whom more frequent monitoring is advised. Here we asked whether CellSearch-detected pulmonary venous CTCs (PV-CTCs) at surgical resection of early-stage NSCLC represent subclones responsible for subsequent disease relapse. PV-CTCs were detected in 48% of 100 patients enrolled into the TRACERx study3, were associated with lung-cancer-specific relapse and remained an independent predictor of relapse in multivariate analysis adjusted for tumor stage. In a case study, genomic profiling of single PV-CTCs collected at surgery revealed higher mutation overlap with metastasis detected 10 months later (91%) than with the primary tumor (79%), suggesting that early-disseminating PV-CTCs were responsible for disease relapse. Together, PV-CTC enumeration and genomic profiling highlight the potential of PV-CTCs as early predictors of NSCLC recurrence after surgery. However, the limited sensitivity of PV-CTCs in predicting relapse suggests that further studies using a larger, independent cohort are warranted to confirm and better define the potential clinical utility of PV-CTCs in early-stage NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Células Neoplásicas Circulantes/patología , Venas Pulmonares/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Genoma Humano/genética , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias
15.
Blood ; 134(18): 1517-1527, 2019 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-31515249

RESUMEN

Mycosis fungoides (MF) is a mature T-cell lymphoma currently thought to develop primarily in the skin by a clonal expansion of a transformed, resident memory T cell. However, this concept does not explain the key characteristics of MF, such as the debut with multiple, widespread skin lesions or inability of skin-directed therapies to provide cure. The testable inference of the mature T-cell theory is the clonality of MF with respect to all rearranged T-cell receptor (TCR) genes. Here, we used a whole-exome sequencing approach to detect and quantify TCR-α, ß, and γ clonotypes in tumor cell clusters microdissected from MF lesions. This method allowed us to calculate the tumor cell fraction of the sample and therefore an unequivocal identification of the TCR clonotypes as neoplastic. Analysis of TCR sequences from 29 patients with MF stage I to IV proved the existence of multiple T-cell clones within the tumor cell fraction, with a considerable variation between patients and between lesions from the same patient (median, 11 clones; range, 2-80 clones/sample). We have also detected multiple neoplastic clones in the peripheral blood in all examined patients. Based on these findings, we propose that circulating neoplastic T-cell clones continuously replenish the lesions of MF, thus increasing their heterogeneity by a mechanism analogous to the consecutive tumor seeding. We hypothesize that circulating neoplastic clones might be a promising target for therapy and could be exploited as a potential biomarker in MF.


Asunto(s)
Micosis Fungoide/patología , Células Neoplásicas Circulantes/patología , Neoplasias Cutáneas/patología , Células Clonales/patología , Humanos
16.
Med Oncol ; 36(10): 89, 2019 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-31520329

RESUMEN

Several clinical studies have examined circulating tumour cells (CTCs). However, the application of CTCs as a predictive/prognostic marker for breast cancer patients has yet to be established, particularly the selection of suitable markers for detecting CTCs. We recently investigated CTCs, including mesenchymal status, from metastatic breast cancer patients who had received eribulin-based treatment. We found that assessment of both mesenchymal and epithelial CTCs might be important for predicting eribulin responsiveness. In the current study, we followed up the outcomes of these patients after eribulin treatment and investigated the possibility of CTC analysis results serving as prognostic markers for this patient population. Twenty-one patients were enrolled and peripheral blood samples were collected before eribulin-based treatments. CTCs were then examined using a Microfluidic Chip device. CTCs positive for vimentin and pan-cytokeratin were defined as mesenchymal and epithelial CTCs, respectively. Overall survival (OS) was assessed in relation to the number of CTCs and clinicopathological factors. During the observation period, 13 patients (62%) died due to breast cancer and the median OS was 18 months. Patients with high-grade tumours and a high total number of CTCs showed significantly shorter OS than those with low-grade tumours and smaller CTC burdens (p = 0.026 and 0.037, respectively). Patients who received eribulin as the first chemotherapy for metastatic disease showed longer OS (p = 0.006). Our data suggest that determining numbers of both mesenchymal and epithelial CTCs might predict survival for patients receiving eribulin.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Furanos/uso terapéutico , Cetonas/uso terapéutico , Células Neoplásicas Circulantes/patología , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/mortalidad , Supervivencia sin Enfermedad , Transición Epitelial-Mesenquimal/efectos de los fármacos , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Vimentina/uso terapéutico
17.
Breast Cancer Res ; 21(1): 101, 2019 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-31481116

RESUMEN

BACKGROUND: The incidence of brain metastases in breast cancer (BCBM) patients is increasing. These patients have a very poor prognosis, and therefore, identification of blood-based biomarkers, such as circulating tumor cells (CTCs), and understanding the genomic heterogeneity could help to personalize treatment options. METHODS: Both EpCAM-dependent (CellSearch® System) and EpCAM-independent Ficoll-based density centrifugation methods were used to detect CTCs from 57 BCBM patients. DNA from individual CTCs and corresponding primary tumors and brain metastases were analyzed by next-generation sequencing (NGS) in order to evaluate copy number aberrations and single nucleotide variations (SNVs). RESULTS: CTCs were detected after EpCAM-dependent enrichment in 47.7% of the patients (≥ 5 CTCs/7.5 ml blood in 20.5%). The CTC count was associated with ERBB2 status (p = 0.029) of the primary tumor as well as with the prevalence of bone metastases (p = 0.021). EpCAM-independent enrichment revealed CTCs in 32.6% of the patients, especially among triple-negative breast cancer (TNBC) patients (70.0%). A positive CTC status after enrichment of either method was significantly associated with decreased overall survival time (p < 0.05). Combining the results of both enrichment methods, 63.6% of the patients were classified as CTC positive. In three patients, the matched tumor tissue and single CTCs were analyzed by NGS showing chromosomal aberrations with a high genomic clonality and mutations in pathways potentially important in brain metastasis formation. CONCLUSION: The detection of CTCs, regardless of the enrichment method, is of prognostic relevance in BCBM patients and in combination with molecular analysis of CTCs can help defining patients with higher risk of early relapse and suitability for targeted treatment.


Asunto(s)
Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Células Neoplásicas Circulantes/patología , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Recuento de Células , Aberraciones Cromosómicas , Variaciones en el Número de Copia de ADN , Molécula de Adhesión Celular Epitelial/metabolismo , Femenino , Humanos , Mutación , Células Neoplásicas Circulantes/metabolismo , Pronóstico , Análisis de Supervivencia
18.
Anal Chim Acta ; 1082: 136-145, 2019 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-31472702

RESUMEN

Circulating tumor cells (CTCs) are expected to serve as a blood-based biomarker in the diagnosis of cancers at an early stage, providing an opportunity to increase the survival of cancer patients. Current techniques for CTC detection were designed for some particular types of cancer with confirmed primary tumor origin. In this work, a platform for the detection of two cancer types and the identification of the primary tumor origin of CTCs was established to meet the requirement of cancer diagnosis and clinical application. A combined strategy based on in vivo capture method using antibody cocktail and multicolor fluorescence imaging using aptamer was designed to achieve the high-efficiency capture of CTCs and the accurate location of the primary tumor. An antibody cocktail of epithelial cell adhesion molecule (EpCAM) and epidermal growth factor receptor (EGFR) was applied to capture breast cancer CTCs and hepatocellular CTCs in vivo. The capture efficiency of hepatocellular CTCs was significantly increased from 3.17% to 26.67% and the capture efficiency of breast cancer CTCs slightly increased from 27.00% to 29.84% compared with EpCAM-based capture of CTCs. Meanwhile, the primary tumor origins of breast cancer CTCs and hepatocellular CTCs were simultaneously distinguished by specific aptamer-based fluorescence probes without any signal crosstalk. The results of in vivo experiments using the dual tumor-bearing mouse model confirmed the feasibility of this method to capture CTCs and identify primary tumor origins. This simple and efficient approach has potential for future applications in cancer diagnosis and prognosis.


Asunto(s)
Aptámeros de Nucleótidos/química , Neoplasias de la Mama/diagnóstico , Neoplasias Hepáticas/diagnóstico , Células Neoplásicas Circulantes/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Animales , Anticuerpos Inmovilizados/inmunología , Neoplasias de la Mama/patología , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Separación Celular/instrumentación , Separación Celular/métodos , Molécula de Adhesión Celular Epitelial/inmunología , Receptores ErbB/inmunología , Femenino , Colorantes Fluorescentes/química , Humanos , Neoplasias Hepáticas/patología , Ratones Endogámicos BALB C , Ratones Desnudos , Microscopía Fluorescente/métodos , Células Neoplásicas Circulantes/inmunología , Conejos
19.
In Vivo ; 33(5): 1615-1620, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31471413

RESUMEN

AIM: To evaluate the clinical efficacy of a circulating tumor cell (CTC) test by comparison between healthy volunteers and patients with localized prostate cancer including those under active surveillance. MATERIALS AND METHODS: CTC counts in peripheral blood were compared between patients with prostate cancer (n=45) and healthy volunteers (n=17). CTCs were identified based on the expression of epithelial cell adhesion molecule (EpCAM) and counted using a SMART BIOPSY™ SYSTEM. RESULTS: The number of EpCAM+ cells was significantly higher in patients with cancer than in healthy volunteers. Among the low-risk patients (n=9), two had up-staging and six had up-grading. Among those up-staged, there was one case which was EpCAM+ Among those cases up-graded, three were EpCAM+ In those with stage T2 tumors, the presence of Gleason pattern 5 was positively correlated with EpCAM positivity (rho=0.59, p<0.001). CONCLUSION: CTC counts in localized prostate cancer were associated with Gleason pattern 5. Active treatment should be considered for patients with low-risk disease during active surveillance who are found to have EpCAM+ CTCs because of a risk of up-staging and up-grading.


Asunto(s)
Células Neoplásicas Circulantes/patología , Neoplasias de la Próstata/diagnóstico , Adulto , Anciano , Biomarcadores de Tumor , Biopsia , Estudios de Casos y Controles , Recuento de Células , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias de la Próstata/terapia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espera Vigilante
20.
Anticancer Res ; 39(9): 4711-4720, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31519570

RESUMEN

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.


Asunto(s)
Amplificación de Genes , Mutación , Células Neoplásicas Circulantes/metabolismo , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Animales , Antineoplásicos/farmacología , Biomarcadores , Biomarcadores de Tumor , Línea Celular Tumoral , Modelos Animales de Enfermedad , Receptores ErbB/genética , Clorhidrato de Erlotinib/farmacología , Xenoinjertos , Humanos , Inmunohistoquímica , Ratones , Células Neoplásicas Circulantes/patología , Neoplasias Gástricas/tratamiento farmacológico
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