Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 142.675
Filtrar
1.
Anticancer Res ; 40(5): 2457-2465, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32366389

RESUMEN

The introduction of tyrosine kinase inhibitors (TKIs) directed against the catalytic activity of the ABL tyrosine kinase has considerably improved the outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease. Indeed, these individuals currently show a life-expectancy comparable to those of healthy subjects. Currently, five TKIs (imatinib, dasatinib, nilotinib, bosutinib and ponatinib) are approved for the treatment of CML and can be used as first, second or further lines of treatment according to disease risk scores, patient comorbidities and the presence of known TKI resistance mechanisms. In fact, 15-20% of all CML patients fail to achieve optimal responses according to the current definitions of the European Leukemia Network and will require sequential TKI treatment to avoid disease progression. In this review, we present the state of art in several crucial areas of CML management by briefly: i) depicting the domain structure of the BCR-ABL1 oncoprotein; ii) describing pivotal data concerning TKI efficacy; iii) illustrating the diverse molecular mechanisms causing TKI resistance; and iv) summarizing new ABL1-directed therapeutic approaches that are presently under investigation.


Asunto(s)
Antineoplásicos/uso terapéutico , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Terapia Molecular Dirigida , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-abl/antagonistas & inhibidores , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor , Resistencia a Antineoplásicos/genética , Proteínas de Fusión bcr-abl/genética , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Humanos , Mutación , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Proteínas Proto-Oncogénicas c-abl/genética , Resultado del Tratamiento
2.
Anticancer Res ; 40(5): 2475-2479, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32366391

RESUMEN

BACKGROUND/AIM: Matrix-producing breast carcinoma (MPBC) is a rare and usually aggressive triple-negative breast cancer (TNBC). In the present report, we determined the drug sensitivity for a triple-negative MPBC using a patient-derived orthotopic xenograft (PDOX) model. MATERIALS AND METHODS: The PDOX model was established in the left 2nd mammary by surgical orthotopic implantation (SOI). MPBC PDOX models were randomized into 4 groups (6 mice per group) when the tumor volume became 80 mm3: G1, control group; G2, cisplatinum group [intraperitoneal (i.p.) injection, weekly, for 2 weeks]; G3, paclitaxel group (i.p., weekly, for 2 weeks); G4, eribulin group [intravenous (i.v.) injection, weekly, for 2 weeks]. All mice were sacrificed on day 15. Tumor volume and body weight were measured one time per week. RESULTS: The MPBC PDOX model was resistant to cisplatinum (p=0.800). Paclitaxel suppressed tumor growth compared to the control group (p=0.009). However, only eribulin regressed the tumor (p=0.001). CONCLUSION: Eribulin has clinical potential for triple-negative MPBC patients.


Asunto(s)
Cisplatino/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Furanos/farmacología , Cetonas/farmacología , Neoplasias de la Mama Triple Negativas/patología , Animales , Biomarcadores de Tumor , Cisplatino/uso terapéutico , Modelos Animales de Enfermedad , Femenino , Furanos/uso terapéutico , Humanos , Cetonas/uso terapéutico , Ratones , Paclitaxel/farmacología , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/etiología , Neoplasias de la Mama Triple Negativas/metabolismo , Carga Tumoral/efectos de los fármacos , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
3.
Anticancer Res ; 40(5): 2487-2495, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32366393

RESUMEN

BACKGROUND/AIM: This study analyzed the gene expression of the "classic" KLK1 and "new" kallikreins KLK4-KLK15, in relation to the molecular characteristics and in vitro invasiveness of 21 breast cancer (BC) and three normal breast-derived cell lines (CLs). MATERIALS AND METHODS: Gene expression of KLKs was determined by using real-time polymerase chain reaction (PCR). The invasiveness of the CLs was examined using a fibroblast-collagen-based in vitro cell culture assay. RESULTS: KLK5 and KLK7-KLK11 were down-regulated in several BCCLs. In contrast, KLK4, KLK8, KLK12 and KLK15 demonstrated strikingly high expression in two BCCLs, UACC 812 and MDA-MB 330. The KLK expression differed frequently according to the presence of androgen receptor (KLK1 and KLK5-KLK9), and occasionally according to estrogen receptor (KLK9) and EGFR (KLK7). Two KLK clusters were detected (first: KLK1, 4, 12, 15; second: all other KLKs), with two subclasses within the second cluster (KLK5-9 and KLK10, 11, 13, and 14). The CLs that expressed at least six KLKs belonged predominantly to basal or HER2 intrinsic subtypes. No KLK predicted the in vitro invasiveness of CLs. CONCLUSION: Gene expression of KLKs was altered in BCCLs. This change was mostly down-regulation and often related to the presence of androgen receptor. The observed clusters point to a possible functional interplay of selected KLKs in BCCLs.


Asunto(s)
Expresión Génica , Calicreínas/genética , Biomarcadores de Tumor , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Perfilación de la Expresión Génica , Humanos , Calicreínas/metabolismo
4.
Anticancer Res ; 40(5): 2537-2548, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32366398

RESUMEN

BACKGROUND/AIM: Radiotherapy-induced autophagy affects radiation-sensitivity and radiotherapy efficacy. Histone modifications also occur during radiotherapy. This study assessed radiotherapy effects on histone modification and autophagy in non-small cell lung cancer (NSCLC) cells. MATERIALS AND METHODS: NSCLC cells were subjected to γ-irradiation. Autophagy was detected using western blotting and acridine orange staining. Radiation effect on cell growth was evaluated by clonogenic assay. Histone modifications were assessed by western blotting. Next generation sequencings (NGSs) were conducted to identify histone modification target genes. RESULTS: Radio-protective autophagy and histone H4 lysine 20 trimethylation (H4K20me3) were up-regulated after irradiation. By NGSs, genes that are differentially expressed upon irradiation were identified, including the candidate H4K20me3 target gene GABARAPL1. Furthermore, we showed that GABARAPL1 is essential for the radiation-induced autophagy. CONCLUSION: Our findings revealed the regulatory axis of radiation-induced H4K20me3-GABARAPL1 in radio-protective autophagy. Modulation of this axis may be a new strategy to enhance radiotherapy efficacy in NSCLC.


Asunto(s)
Autofagia/efectos de la radiación , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Histonas/metabolismo , Neoplasias Pulmonares/metabolismo , Lisina/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Línea Celular Tumoral , Epigénesis Genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , Metilación , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , ARN Interferente Pequeño/genética
5.
Tumour Biol ; 42(5): 1010428320919198, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32364828

RESUMEN

Detection of circulating tumor DNA is a new noninvasive technique with potential roles in diagnostic, follow-up, and prognostic evaluation of patients with many types of solid tumors. We aimed to evaluate the role of circulating tumor DNA in the setting of metastatic ovarian carcinoma. A prospective cohort of patients with metastatic ovarian cancer who were referred to systemic therapy was enrolled. Blood samples were collected before the start of treatment and monthly thereafter for 6 months. Circulating tumor DNA was quantified by real-time quantitative reverse transcription polymerase chain reaction of different lengths of Arthrobacter luteus elements as described by Umetani et al. A total of 11 patients were included, 2 for primary disease and 9 for recurrent disease. After the first cycle of chemotherapy, patients whose circulating tumor DNA levels increased from baseline were more likely to respond to chemotherapy than those whose circulating tumor DNA levels did not increase (p = 0.035). Furthermore, patients whose circulating tumor DNA levels rose after the first cycle of chemotherapy also had improved disease-free survival compared to those whose circulating tumor DNA levels did not increase (p = 0.0074). We conclude that the increase in circulating tumor DNA values collected in peripheral blood after the first cycle of systemic treatment in patients with advanced ovarian cancer is associated with an early response to systemic treatment and correlates with superior disease-free survival in this population. Circulating tumor DNA might be a specific, noninvasive, and cost-effective new biomarker of early response to systemic treatment in these patients.


Asunto(s)
Biomarcadores de Tumor , ADN Tumoral Circulante , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Anciano , Manejo de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/terapia , Proyectos Piloto , Pronóstico , Tiempo de Tratamiento , Resultado del Tratamiento
6.
Tumour Biol ; 42(5): 1010428320918404, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32364878

RESUMEN

Base excision repair, which is initiated by the DNA N-glycosylase proteins, is the frontline for repairing potentially mutagenic DNA base damage. Several base excision repair genes are deregulated in cancer and affect cellular outcomes to chemotherapy and carcinogenesis. Endonuclease VIII-like 3 (NEIL3) is a DNA glycosylase protein that is involved in oxidative and interstrand crosslink DNA damage repair. Our previous work has showed that NEIL3 is required to maintain replication fork integrity. It is unknown whether NEIL3 overexpression could contribute to cancer phenotypes, and its prognostic value and use as potential drug target remain unexplored. Our analysis of cancer genomics data sets reveals that NEIL3 frequently undergoes overexpression in several cancers. Furthermore, patients who exhibited NEIL3 overexpression with pancreatic adenocarcinoma, lung adenocarcinoma, lower grade glioma, kidney renal clear cell carcinoma, and kidney papillary cell carcinoma had worse overall survival. Importantly, NEIL3 overexpressed tumors accumulate mutation and chromosomal variations. Furthermore, NEIL3 overexpressed tumors exhibit simultaneous overexpression of homologous recombination genes (BRCA1/2) and mismatch repair genes (MSH2/MSH6). However, NEIL3 overexpression is negatively correlated with tumor overexpressing nucleotide excision repair genes (XPA, XPC, ERCC1/2). Our results suggest that NEIL3 might be a potential prognosis marker for high-risk patients, and/or an attractive therapeutic target for selected cancers.


Asunto(s)
Biomarcadores de Tumor , Expresión Génica , Variación Genética , N-Glicosil Hidrolasas/genética , Neoplasias/genética , Neoplasias/mortalidad , Línea Celular Tumoral , Variaciones en el Número de Copia de ADN , Daño del ADN , Reparación del ADN , Humanos , Estimación de Kaplan-Meier , Mutación , Neoplasias/diagnóstico , Pronóstico
7.
Medicine (Baltimore) ; 99(19): e19957, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32384443

RESUMEN

Studies of PDPN in cancers have focused on the interactions with palates through the binding with CECL-2 which mainly express on palates and immune cells, while little is known on its interactions with immune cells.PDPN expression in cancers was analyzed through Oncomine, GEPIA, and TIMER database. Prognostic value (HR, P value from log-rank test) was evaluated through Kaplan-Meier plotter and OncoLnc database. The correlations between PDPN and the infiltrating levels of immune cells in different cancers, and diverse immune markers in gastric cancer were investigated through TIMER database.High PDPN expression predicted poor overall survival (OS) and post-progression survival (PPS) particularly in gastric cancer (OS P = .0089; PPS P = .00085), especially among patients with Her-2 (+) and lymph node metastasis. In addition, PDPN was positively correlated with infiltrating levels of immune cells, other than B cells in gastric cancer. However, PDPN showed more correlations with immune markers of M2 type TAM (CD163, VSIG4, MS4A4A) and T cell exhaustion (TIM-3, TOX, and GZMB).These findings all suggest that high PDPN predicts poor survival outcomes, especially for Her-2 (+) gastric cancer patients. Though inducing M2 type TAM and T cell exhaustion, high PDPN can predict high levels of various immune cells infiltration in STAD. Those correlations may bring new ideas to immunology treatment for gastric cancer patients who do not benefit from the existing immune checkpoint inhibitors.


Asunto(s)
Linfocitos Infiltrantes de Tumor/metabolismo , Glicoproteínas de Membrana/inmunología , Glicoproteínas de Membrana/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/inmunología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Bases de Datos Factuales , Femenino , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática/genética , Masculino , Pronóstico , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/mortalidad
8.
Medicine (Baltimore) ; 99(18): e20044, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32358386

RESUMEN

Colorectal cancer (CRC) patients have been shown to express a cytokine signature that is detectable in serum and contributes to cancer pathogenesis. The objective of this study was to evaluate the potential clinical significance of preoperative circulating cytokine levels in CRC patients.The expression of serum B7-H1 and IL-10 was assessed by ELISA in 89 patients and 64 health volunteers. As a control marker, CEA serum levels were measured by electrochemical luminescence detection. The receiver operating characteristic (ROC) curve was used to analysis to demonstrate the potential diagnostic value of these biomarkers.The expression of serum B7-H1 was significantly increased in CRC patients (P = .001) and associated with the progression of TNM stage and a positive association with serum IL-10 levels was also evident. Furthermore, serum B7-H1 and IL-10 expression was not influenced by age, gender, tumor location, or mass, whereas a relationship existed with tumor metastasis and TNM stage. The serum levels of B7-H1 and IL-10 on the 7th postoperative day were significantly decreased compared with that of preoperative serum levels (P = .001, P = .003 respectively). The area under the ROC curves (AUC) for B7-H1 and IL-10 were 0.7063 and 0.5706, respectively. The optimal sensitivity and specificity of B7-H1 for discriminating between colon cancer patients and healthy controls were 85.21% and 56.43%, respectively, using a cut-off value of 3.46 ng/mL. However, the combined ROC analysis using B7-H1 and IL-10 revealed an AUC of 0.8791, with a sensitivity of 90.63% and a specificity of 75.18%.The outcomes of the present study demonstrate the clinical significance of serum B7-H1 and IL-10 concentrations. Combined detection of B7-H1 plus IL-10 showed significantly increased sensitivity and specificity for discriminating between colorectal cancer patients and healthy controls compared these markers detection individual. The measurement of B7-H1 or IL-10 in sera following surgery may provide an additional tool for assessing the curative effects of surgery in CRC patients.


Asunto(s)
Antígeno B7-H1/sangre , Neoplasias Colorrectales/sangre , Interleucina-10/sangre , Anciano , Biomarcadores de Tumor , Antígeno Carcinoembrionario/sangre , Neoplasias Colorrectales/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Curva ROC , Sensibilidad y Especificidad
9.
Anticancer Res ; 40(5): 2627-2635, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32366407

RESUMEN

BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) is an aggressive head and neck malignancy. The aim of this study was to elucidate the role of periostin (POSTN) in the epithelial-to-mesenchymal transition (EMT) process mediating the acquisition of radioresistance in HNSCC. MATERIALS AND METHODS: The expression levels of EMT hallmark genes including POSTN and Erk/Akt signaling pathways were compared between radiosensitive and radioresistant HNSCC cells. RESULTS: POSTN mRNA expression was higher in radioresistant HNSCC cells, and silencing POSTN significantly impaired their invasiveness under the effect of EMT process represented by up-regulation of mesenchymal markers and down-regulation of an epithelial marker. Expression levels of Erk and Akt were higher in radioresistant cells. CONCLUSION: POSTN in association with the Erk and Akt signaling pathways was up-regulated during the EMT process, leading to the conversion of radiosensitive to radioresistant HNSCC cells. POSTN may be a key marker for predicting the radioresistance and therapeutic target of HNSCC.


Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Transición Epitelial-Mesenquimal , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Tolerancia a Radiación , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Regulación hacia Abajo , Epitelio/metabolismo , Epitelio/patología , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Humanos , Mesodermo/patología , Invasividad Neoplásica , Tolerancia a Radiación/genética , Transducción de Señal/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología
10.
Int J Mol Sci ; 21(7)2020 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-32276343

RESUMEN

MicroRNAs (miRNAs) are small and non-coding RNAs that display aberrant expression in the tissue and plasma of cancer patients when tested in comparison to healthy individuals. In past decades, research data proposed that miRNAs could be diagnostic and prognostic biomarkers in cancer patients. It has been confirmed that miRNAs can act either as oncogenes by silencing tumor inhibitors or as tumor suppressors by targeting oncoproteins. MiR-144s are located in the chromosomal region 17q11.2, which is subject to significant damage in many types of cancers. In this review, we assess the involvement of miR-144s in several cancer types by illustrating the possible target genes that are related to each cancer, and we also briefly describe the clinical applications of miR-144s as a diagnostic and prognostic tool in cancers.


Asunto(s)
Biomarcadores de Tumor/análisis , MicroARNs/metabolismo , Neoplasias/metabolismo , Animales , Regulación Neoplásica de la Expresión Génica , Genes Relacionados con las Neoplasias , Humanos , MicroARNs/análisis , MicroARNs/genética , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Pronóstico
11.
Adv Exp Med Biol ; 1220: 61-80, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32304080

RESUMEN

Metastasis is the major cause of breast cancer death worldwide. In metastatic breast cancer, circulating tumor cells (CTCs) can be captured from patient blood samples sequentially over time and thereby serve as surrogates to assess the biology of surviving cancer cells that may still persist in solitary or multiple metastatic sites following treatment. CTCs may thus function as potential real-time decision-making guides for selecting appropriate therapies during the course of disease or for the development and testing of new treatments. The heterogeneous nature of CTCs warrants the use of single cell platforms to better inform our understanding of these cancer cells. Current techniques for single cell analyses and techniques for investigating interactions between cancer and immune cells are discussed. In addition, methodologies for growing patient-derived CTCs in vitro or propagating them in vivo to facilitate CTC drug testing are reviewed. We advocate the use of CTCs in appropriate microenvironments to appraise the effectiveness of cancer chemotherapies, immunotherapies, and for the development of new cancer treatments, fundamental to personalizing and improving the clinical management of metastatic breast cancer.


Asunto(s)
Neoplasias de la Mama/patología , Evaluación Preclínica de Medicamentos , Metástasis de la Neoplasia/patología , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Medicina de Precisión , Análisis de la Célula Individual , Biomarcadores de Tumor , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Toma de Decisiones Clínicas , Humanos , Metástasis de la Neoplasia/diagnóstico
12.
Adv Exp Med Biol ; 1220: 117-134, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32304083

RESUMEN

Liquid biopsy based on the analysis of circulating tumor cells (CTCs) has emerged as an important field of research. Molecular characterization of CTCs can provide insights into cancer biology and biomarkers for the clinic, representing a non-invasive powerful tool for monitoring breast cancer metastasis and predict the therapeutic response. Epigenetic mechanisms play a key role in the control of gene expression and their alteration contributes to cancer development and progression. These epigenetic modifications in CTCs have been described mainly related to modifications of the DNA methylation pattern and changes in the expression profile of noncoding RNAs. Here we summarize the recent findings on the epigenetic characterization of CTCs in breast cancer and their clinical value as tumor biomarkers, and discuss challenges and opportunities in this field.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Epigénesis Genética , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Biomarcadores de Tumor , Metilación de ADN , Humanos , Metástasis de la Neoplasia/genética , Metástasis de la Neoplasia/patología , ARN no Traducido/genética
13.
Adv Exp Med Biol ; 1220: 135-146, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32304084

RESUMEN

Breast cancer is the most common malignancy among women. Most of breast cancer patients are diagnosed in early stages and will be treated with curative intent. Despite this, some patients will relapse. The identification of patients at high risk remains an important challenge. CTCs can be useful to identify this patients, to assess tumor dynamics and to monitoring therapy. There is definitive evidence on the prognostic role of CTCs in early breast cancer (eBC) but its clinical utility in daily practice is still lacking. We have to take into consideration that the studies published to date mainly evaluated the presence of CTC based on the expression of epithelial surface markers. Future studies need to overcome this limitation and important advances in technical methods can assess CTCs and capture the heterogeneity of the tumor landscape. It is also tempting to speculate that CTCs may also provide complementary information on the interplay of tumor cells with the immune system. The combination of different methods to detect tumoral disease by liquid biopsy may provide new ways to personalize in an unprecedented manner the management of patients with eBC.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Células Neoplásicas Circulantes/patología , Edad de Inicio , Biomarcadores de Tumor , Neoplasias de la Mama/inmunología , Femenino , Humanos , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/patología , Células Neoplásicas Circulantes/inmunología , Pronóstico
14.
Adv Exp Med Biol ; 1220: 147-164, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32304085

RESUMEN

Precision medicine through liquid biopsy represents an emerging approach in the management of cancer. The CTC count in blood samples from patients with advanced breast cancer is a powerful prognostic factor for both progression free and overall survival. Moreover, high levels of CTCs at any time during the treatment can reliably predict progression before imaging studies and/or tumor markers. Furthermore, there are works on the molecular characterization of the CTCs and their potential ability to guide the treatment in a dynamic way. However, their role remains controversial. Detection and enumeration of CTCs is variable among different tumors and is subjected to biases related mainly to their methodology, which is not completely standardized. In addition, they must demonstrate their clinical value to guide the treatment and a translation on patient's survival.


Asunto(s)
Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Células Neoplásicas Circulantes/patología , Biomarcadores de Tumor , Neoplasias de la Mama/diagnóstico , Progresión de la Enfermedad , Humanos , Biopsia Líquida , Células Neoplásicas Circulantes/metabolismo , Tasa de Supervivencia
15.
Medicine (Baltimore) ; 99(16): e19829, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32312004

RESUMEN

As a biomarker, neuron-specific enolase (NSE) has been widely recognized in the diagnosis of benign diseases and malignant tumors. This study aimed to investigate the potential diagnostic value of NSE in patients with gastric adenocarcinoma.Serum levels of the NSE were compared between 219 patients with gastric adenocarcinoma and 298 healthy individuals, NSE and clinicopathological parameters were analyzed. Meanwhile, to evaluate the diagnostic capability of NSE, the receiver operating characteristic (ROC), and area under curve (AUC) was calculated.In the present study, the median serum NSE level of the patient group was 20.770 ng/mL, which was higher than that of the control group 15.625 ng/mL (P < .05). Serum NSE level in patients group compared with healthy control was statistically significant (P < .05). Serum NSE level was associated with pathological tumor-node-metastasis (pTNM) staging, lymph node metastasis, and distant metastasis in patients with gastric adenocarcinoma. Besides, the AUC of NSE in gastric adenocarcinoma was 0.742, which was higher than those of the other 3 markers (0.573-0.644). Besides, the AUC of the combined 4 markers was higher than any individual marker (0.778).Serum NSE detecting may have good value for diagnosis of gastric adenocarcinoma. Besides, the combination of NSE, CEA, CA19-9, and CA242 performed even better than any single marker. Thus, the combined detection of the 4 tumor markers may be more useful for the diagnosis of gastric adenocarcinoma.


Asunto(s)
Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Fosfopiruvato Hidratasa/sangre , Neoplasias Gástricas/patología , Adulto , Anciano , Antígenos de Carbohidratos Asociados a Tumores/sangre , Antígeno CA-19-9/sangre , Antígeno Carcinoembrionario/sangre , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Sensibilidad y Especificidad
16.
An Acad Bras Cienc ; 92(1): e20181203, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32321013

RESUMEN

Circulating miRNAs presenting in plasma in a stable manner have been demonstrated their potential role as a promising biomarkers in many human diseases, such as Alzheimer's disease, melanoma and ovarian carcinoma. However, few circulating miRNAs could be used for breast ductal cancer diagnosis. Here, we identified miR-1273g-3p as a biomarker for detecting breast ductal cancer. We detected miR-1273g-3p levels in the plasma of 39 sporadic breast ductal cancer patients and 40 healthy donors by Stem-loop Quantitative Real-time PCR (qRT-PCR). The results showed the plasma miR-1273g-3p level were significantly up-regulated in breast ductal cancer patients compared with healthy donors (p=0.0139). Receiver operating characteristic (ROC) curve also revealed the significantly diagnostic ability of miR-1273g-3p in patients (p=0.0414). In addition, the plasma level of miR-1273g-3p was closely related to IIIB-IIIC TNM stage. We also confirmed the higher expression level of miR-1273g-3p in breast cancer cell lines MCF-7 (4.872±0.537) than normal breast cells (Hs 578Bst). Taken together, miR-1273g-3p could represent as a potential biomarker for early breast ductal cancer diagnosis.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Carcinoma Intraductal no Infiltrante/diagnóstico , MicroARNs/sangre , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Carcinoma Intraductal no Infiltrante/sangre , Detección Precoz del Cáncer , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad
17.
Medicine (Baltimore) ; 99(16): e19755, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32311975

RESUMEN

Although proliferating cell nuclear antigen (PCNA) plays an important role in tumor proliferation and its expression level is closely related to the biological activity of tumor cells, PCNA expression in non-small cell lung cancer (NSCLC) has been seldom reported. In this study, we aimed to investigate the significance of PCNA expression in NSCLC tissues. PCNA expression in NSCLC and adjacent tissues were assessed by immunohistochemistry (IHC), western blotting, and reverse transcription polymerase chain reaction. Single factor analysis was used to study the relationship between the expression of PCNA and clinicopathological features of NSCLC. Multi-factor Cox survival analysis was used to evaluate the relationship between the expression of PCNA and overall survival of postoperative NSCLC patients. The areas under the receiver operating characteristics were calculated to evaluate the value of PCNA expression level in predicting the 3-year survival of NSCLC patients. IHC analysis showed that the positive expression rates of PCNA protein in NSCLC and adjacent tissues were 91.79% (257/280) and 25.83% (31/120), respectively. Western blotting confirmed that PCNA protein level was significantly higher in NSCLC tissues than in the adjacent tissues (P < .05). Reverse transcription polymerase chain reaction showed that the positive rate of PCNA mRNA in NSCLC was 88.93% (249/280), which was significantly higher than that in adjacent tissues 29.17% (35/120) (P < .05). Both PCNA mRNA and protein levels were correlated with tumor differentiation, size, metastasis, and stage in NSCLC. Patients exhibiting higher PCNA protein expression had a significantly shorter disease-specific survival rate than the other patients. PCNA protein level and tumor pathological type, metastasis, differentiation degree, and stage were independent factors affecting the overall survival of postoperative patients. The areas under the receiver operating characteristics of PCNA mRNA for predicting the 3-year survival of NSCLC patients was 0.89 (0.79-0.98), with a sensitivity and specificity of 0.84 and 0.76, respectively. In conclusion, high PCNA protein and mRNA levels may be associated with the occurrence, development, and prognosis of NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , China/epidemiología , Estudios Transversales , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
18.
Medicine (Baltimore) ; 99(16): e19796, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32311993

RESUMEN

This study investigated the diagnostic value of preoperative serum neuro-specific enolase (NSE) in gastric cancer (GC) and colorectal cancer (CRC), and the diagnostic viability of combined serum NSE, carcinoembryonic antigen (CEA), cancer antigen (CA)19-9, and CA242.Patients with GC and CRC, and a healthy control group (n = 666 and 266, respectively) were compared with regard to NSE, CEA, CA19-9, and CA242 serum levels. NSE was analyzed for associations with clinicopathological parameters. To estimate the diagnostic potential of NSE, a receiver operating characteristic curve was constructed and the area under the curve (AUCs) was calculated for different patient subgroups.The median serum NSE level of the tumor group (20.925 ng/mL) was significantly higher than that of the control (15.190 ng/mL). Serum NSE was associated with pathological tumor-node-metastasis staging, lymph node metastasis, distant metastasis, vascular invasion, and nerve infiltration. The area under the receiver operating characteristic curve (AUC) for NSE in GC and CRC (0.769) was higher than for the other 3 markers (0.571-0.680). The AUC of the combined markers was higher than for any of the markers individually (0.778-0.810).The AUC for NSE alone suggests it may be an independent tumor marker, and useful for diagnosis of GC and CRC. However, the AUC for combined NSE, CEA, CA19-9, and CA242 was higher and thus potentially more diagnostic value.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias Colorrectales/sangre , Fosfopiruvato Hidratasa/sangre , Neoplasias Gástricas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Neoplasias Colorrectales/patología , Femenino , Humanos , Modelos Logísticos , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/patología , Adulto Joven
19.
Aging (Albany NY) ; 12(8): 6518-6535, 2020 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-32339157

RESUMEN

Angiotensin-converting enzyme 2 (ACE2) is a member of the renin-angiotension system, however, the correlation between ACE2 and prognosis in UCEC (Uterine Corpus Endometrial Carcinoma) and KIRP (Kidney Renal Papillary Cell Carcinoma) is not clear. We analyzed the expression levels of ACE2 in the Oncomine and TIMER databases, the correlation between ACE2 and overall survival in the PrognoScan, GEPIA and Kaplan-Meier plotter databases. The correlation between ACE2 and immune infiltration level and the type markers of immune cells was investigated in TIMER database. A prognosis analysis based on the expression levels of ACE2 was further performed in related immune cells subgroup. The ACE2 promoter methylation profile was tested in the UALCAN database. In addition, we used GSE30589 and GSE52920 databases to elucidate the changes of ACE2 expression in vivo and in vitro after SARS-CoV infection. ACE2 was elevated in UCEC and KIRP, and high ACE2 had a favorable prognosis. The expression of ACE2 was positively correlated with the level of immune infiltration of macrophage in KIRP, B cell, CD4+T cell, neutrophil and dendritic cell immune infiltration levels in UCEC. ACE2 was significantly positively correlated with the type markers of B cells and neutrophils, macrophages in UCEC, while ACE2 in KIRP was positively correlated with the type markers of macrophages. High ACE2 expression level had a favorable prognosis in different enriched immune cells subgroups in UCEC and KIRP. And the promoter methylation levels of ACE2 in UCEC and KIRP were significantly reduced. What's more, we found that the expression of ACE2 decreased in vivo and in vitro after SARS-CoV infection. In conclusion, ACE2 expression increased significantly in UCEC and KIRP, elevated ACE2 was positively correlated with immune infiltration and prognosis. Moreover, tumor tissues may be more susceptible to SARS-CoV-2 infection in COVID-19 patients with UCEC and KIRP, which may worsen the prognosis.


Asunto(s)
Betacoronavirus , Carcinoma de Células Renales , Infecciones por Coronavirus , Neoplasias Endometriales , Inmunidad Celular , Neoplasias Renales , Pandemias , Peptidil-Dipeptidasa A/biosíntesis , Neumonía Viral , Biomarcadores de Tumor , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/mortalidad , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/metabolismo , Neoplasias Endometriales/inmunología , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/mortalidad , Femenino , Humanos , Neoplasias Renales/inmunología , Neoplasias Renales/metabolismo , Neoplasias Renales/mortalidad , Neumonía Viral/inmunología , Neumonía Viral/metabolismo , Pronóstico
20.
Ann Hematol ; 99(5): 991-1006, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32253454

RESUMEN

Separase, a cysteine endopeptidase, is a key player in mitotic sister chromatid separation, replication fork dynamics, and DNA repair. Aberrant expression and/or altered separase proteolytic activity are associated with aneuploidy, tumorigenesis, and disease progression. Since genomic instability and clonal evolution are hallmarks of progressing chronic myeloid leukemia (CML), we have comparatively examined separase proteolytic activity in TKI-treated chronic phase CML. Separase proteolytic activity was analyzed on single cell level in 88 clinical samples and in 14 healthy controls by a flow cytometric assay. In parallel, BCR-ABL1 gene expression and replication fork velocity were measured by qRT-PCR and DNA fiber assays, respectively. The separase activity distribution (SAD) value indicating the occurrence of MNCs with elevated separase proteolytic activity within samples was found to positively correlate with BCR-ABL1 gene expression levels and loss of MMR (relapse) throughout routine BCR-ABL1 monitoring. Analyses of CD34+ cells and MNCs fractionized by flow cytometric cell sorting according to their separase activity levels (H- and L-fractions) revealed that CD34+ cells with elevated separase activity levels (H-fractions) displayed enhanced proliferation/viability when compared with cells with regular (L-fraction) separase activity (mean 3.3-fold, p = 0.0011). BCR-ABL1 gene expression positivity prevailed in MNC H-fractions over L-fractions (42% vs. 8%, respectively). Moreover, expanding CD34+ cells of H-fractions showed decreased replication fork velocity compared with cells of L-fractions (p < 0.0001). Our data suggests an association between high separase activity, residual BCR-ABL1 gene expression, and enhanced proliferative capacity in hematopoietic cells within the leukemic niche of TKI-treated chronic phase CML.


Asunto(s)
Antígenos CD34/metabolismo , Biomarcadores de Tumor/metabolismo , Proliferación Celular/efectos de los fármacos , Leucemia Mielógena Crónica BCR-ABL Positiva , Inhibidores de Proteínas Quinasas/administración & dosificación , Separasa/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Proteínas de Fusión bcr-abl/metabolismo , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/enzimología , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA