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1.
Adv Exp Med Biol ; 1306: 61-80, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33959906

RESUMEN

Bladder cancer (BC) is one of the most common tumor with high incidence. Relative to other cancers, BC has a high rate of recurrence, which results in increased mortality. As a result, early diagnosis and life-long monitoring are clinically significant for improving the long-term survival rate of BC patients. At present, the main methods of BC detection are cystoscopy and biopsy; however, these procedures can be invasive and expensive. This can lead to patient refusal and reluctance for monitoring. There are several BC biomarkers that have been approved by the FDA, but their sensitivity, specificity, and diagnostic accuracy are not ideal. More research is needed to identify suitable biomarkers that can be used for early detection, evaluation, and observation. There has been heavy research in the proteomics and genomics of BC and many potential biomarkers have been found. Although the advent of metabonomics came late, with the recent development of advanced analytical technology and bioinformatics, metabonomics has become a widely used diagnostic tool in clinical and biomedical research. It should be emphasized that despite progress in new biomarkers for BC diagnosis, there remains challenges and limitations in metabonomics research that affects its translation into clinical practice. In this chapter, the latest literature on BC biomarkers was reviewed.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Biomarcadores de Tumor/genética , Cistoscopía , Humanos , Metabolómica , Recurrencia Local de Neoplasia , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/terapia
2.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(3): 263-271, 2021 Mar 28.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-33927073

RESUMEN

OBJECTIVES: Clarifying the expression of breast cancer receptor is the key to clinical treatment for breast cancer. This study aims to explore the correlation between X-ray and clinical characteristics of 4 molecular subtypes and their receptor types of breast cancer. METHODS: A total of 439 breast cancer patients who confirmed by pathology and performed X-ray examination were enrolled. The X-ray and clinical characteristics of 4 molecular subtypes and the expression of their receptors were analyzed. RESULTS: Luminal A type showed the highest proportion of spiculate masses, and the lowest calcification score, showing significant difference with other 3 subtypes (all P<0.001). The age in the human epidermal growth factor 2 (HER2) overexpression type group was older, the proportions of menopause, the calcification score, and the calcification score with 9-12 were higher, the sizes of the tumor were greater in the HER2 overexpression type group than those in the other 3 molecular subtype groups (age P<0.05, the rest P<0.01). The proportions of regular shape, edge indistinct, and high-grade invasive ductal carcinoma in the triple-negative type group were higher than those in the other 3 molecular subtype groups (all P<0.001). The proportions of non-menopausal patients and spiculate tumors in the estrogen receptor (ER) positive and/or progesterone receptor (PR) positive groups were higher than those in both ER and PR negative group (P<0.001 and P=0.001, respectively). The proportions of calcification fraction and high-grade invasive ductal carcinoma were higher, tumor sizes were greater in the HER2 positive group, Ki-67≥20% group than those in the HER2 negative group, Ki-67<20% group, respectively (P<0.001 or P<0.05, respectively). CONCLUSIONS: Four molecular subtypes of breast cancer and their receptor expressions are correlated with X-ray and clinical characteristics, which can provide a basis for clinical diagnosis and treatment.


Asunto(s)
Neoplasias de la Mama , Biomarcadores de Tumor , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/genética , Femenino , Humanos , Receptor ErbB-2/genética , Receptores Estrogénicos , Receptores de Progesterona , Rayos X
3.
Medicine (Baltimore) ; 100(17): e25715, 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33907159

RESUMEN

ABSTRACT: The tumor microenvironment (TME) plays an important role in the development of breast cancer. Due to limitations in experimental conditions, the molecular mechanism of TME in breast cancer has not yet been elucidated. With the development of bioinformatics, the study of TME has become convenient and reliable.Gene expression and clinical feature data were downloaded from The Cancer Genome Atlas database and the Molecular Taxonomy of Breast Cancer International Consortium database. Immune scores and stromal scores were calculated using the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data algorithm. The interaction of genes was examined with protein-protein interaction and co-expression analysis. The function of genes was analyzed by gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes analysis and gene set enrichment analysis. The clinical significance of genes was assessed with Kaplan-Meier analysis and univariate/multivariate Cox regression analysis.Our results showed that the immune scores and stromal scores of breast invasive ductal carcinoma (IDC) were significantly lower than those of invasive lobular carcinoma. The immune scores were significantly related to overall survival of breast IDC patients and both the immune and stromal scores were significantly related to clinical features of these patients. According to the level of immune/stromal scores, 179 common differentially expressed genes and 5 hub genes with prognostic value were identified. In addition, the clinical significance of the hub genes was validated with data from the molecular taxonomy of breast cancer international consortium database, and gene set enrichment analysis analysis showed that these hub genes were mainly enriched in signaling pathways of the immune system and breast cancer.We identified five immune-related hub genes with prognostic value in the TME of breast IDC, which may partly determine the prognosis of breast cancer and provide some direction for development of targeted treatments in the future.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama , Carcinoma Ductal , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral , Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Carcinoma Ductal/genética , Carcinoma Ductal/inmunología , Carcinoma Ductal/patología , Bases de Datos Genéticas , Femenino , Perfilación de la Expresión Génica/métodos , Ontología de Genes , Humanos , Estimación de Kaplan-Meier , Terapia Molecular Dirigida/métodos , Invasividad Neoplásica/genética , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología
4.
Arch. argent. pediatr ; 119(2): e149-e152, abril 2021. tab
Artículo en Español | LILACS, BINACIS | ID: biblio-1152046

RESUMEN

Los tumores ováricos, a diferencia de lo que sucede en la edad adulta, son infrecuentes en la población pediátrica. Predomina la estirpe germinal, con altas tasas de supervivencia. El objetivo de este estudio es presentar la epidemiología, clínica, diagnóstico y tratamiento de las pacientes de 0-15 años con diagnóstico, entre 2007 y 2017, de tumor ovárico en nuestro centro. Fueron 8 los casos encontrados de 171 tumores diagnosticados (el 4,7 %), con edad media de presentación de 12,5 años. Predominaban, al momento del debut, alteraciones menstruales, dolor abdominal y aumento de perímetro abdominal. Fueron de tipo germinal 6/8, y el teratoma maduro fue el más frecuente. Todas se diagnosticaron con ecografía abdominal, y se confirmó el diagnóstico en 7/8 con resonancia magnética. Se intervinieron todos los casos; predominó la salpingo-ooforectomía, y una paciente precisó quimioterapia adyuvante. La supervivencia libre de enfermedad fue del 100 %.


Unlike adults, ovarian tumors are infrequent in the pediatric population, predominating the germ line at this age, with high survival rates. The objective is to present the epidemiological, clinical, diagnosis and therapeutic characteristics of 0 to 15-year-old patients diagnosed with ovarian tumor in our center between 2007 and 2017.Eight cases out of 171 diagnosed tumors (4.7 %) were found, with a mean age of presentation of 12.5 years. At the moment of diagnosis, menstrual disturbances, abdominal pain and an increase in abdominal circumference predominated. Six out of eight were germ cell tumors, being the mature teratoma the most frequent one. All cases were diagnosed with abdominal ultrasound scan, confirmed in 7/8 cases with magnetic resonance imaging. All cases underwent surgery, predominating salpingo-oophorectomy with one patient requiring adjuvant chemotherapy. Disease-free survival was 100 %.


Asunto(s)
Humanos , Femenino , Niño , Adolescente , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias de Células Germinales y Embrionarias , Neoplasias Ováricas/cirugía , Biomarcadores de Tumor , Estudios Retrospectivos , Salpingooforectomía
5.
World J Surg Oncol ; 19(1): 123, 2021 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-33865399

RESUMEN

BACKGROUND: Pancreatic cancer (PAC) is one of the most devastating cancer types with an extremely poor prognosis, characterized by a hypoxic microenvironment and resistance to most therapeutic drugs. Hypoxia has been found to be one of the factors contributing to chemoresistance in PAC, but also a major driver of the formation of the tumor immunosuppressive microenvironment. However, the method to identify the degree of hypoxia in the tumor microenvironment (TME) is incompletely understood. METHODS: The mRNA expression profiles and corresponding clinicopathological information of PAC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, respectively. To further explore the effect of hypoxia on the prognosis of patients with PAC as well as the tumor immune microenvironment, we established a hypoxia risk model and divided it into high- and low-risk groups in line with the hypoxia risk score. RESULTS: We established a hypoxia risk model according to four hypoxia-related genes, which could be used to demonstrate the immune microenvironment in PAC and predict prognosis. Moreover, the hypoxia risk score can act as an independent prognostic factor in PAC, and a higher hypoxia risk score was correlated with poorer prognosis in patients as well as the immunosuppressive microenvironment of the tumor. CONCLUSIONS: In summary, we established and validated a hypoxia risk model that can be considered as an independent prognostic indicator and reflected the immune microenvironment of PAC, suggesting the feasibility of hypoxia-targeted therapy for PAC patients.


Asunto(s)
Hipoxia/genética , Neoplasias Pancreáticas/genética , Microambiente Tumoral , Biomarcadores de Tumor/genética , Bases de Datos Genéticas , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Neoplasias Pancreáticas/patología , Pronóstico
6.
Int J Mol Sci ; 22(6)2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33808599

RESUMEN

The study of metabolic deregulation in myeloid malignancies has led to the investigation of metabolic-targeted therapies considering that cells undergoing leukemic transformation have excessive energy demands for growth and proliferation. However, the most difficult challenge in agents targeting metabolism is to determine a window of therapeutic opportunities between normal and neoplastic cells, considering that all or most of the metabolic pathways important for cancer ontogeny may also regulate physiological cell functions. Targeted therapies have used the properties of leukemic cells to produce altered metabolic products when mutated. This is the case of IDH1/2 mutations generating the abnormal conversion of α-ketoglutarate (KG) to 2-hydroxyglutarate, an oncometabolite inhibiting KG-dependent enzymes, such as the TET family of genes (pivotal in characterizing leukemia cells either by mutations, e.g., TET2, or by altered expression, e.g., TET1/2/3). Additional observations derive from the high sensitivity of leukemic cells to oxidative phosphorylation and its amelioration using BCL-2 inhibitors (Venetoclax) or by disrupting the mitochondrial respiration. More recently, nicotinamide metabolism has been described to mediate resistance to Venetoclax in patients with acute myeloid leukemia. Herein, we will provide an overview of the latest research on the link between metabolic pathways interactome and leukemogenesis with a comprehensive analysis of the metabolic consequences of driver genetic lesions and exemplificative druggable pathways.


Asunto(s)
Biomarcadores de Tumor , Susceptibilidad a Enfermedades , Metabolismo Energético , Mutación , Trastornos Mieloproliferativos/etiología , Trastornos Mieloproliferativos/metabolismo , Animales , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Humanos , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismo , Redes y Vías Metabólicas , Metabolómica , Trastornos Mieloproliferativos/patología , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo
7.
Int J Mol Sci ; 22(6)2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33808647

RESUMEN

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. HCC is associated with several etiological factors, including HBV/HCV infections, cirrhosis, and fatty liver diseases. However, the molecular mechanism underlying HCC development remains largely elusive. The advent of high-throughput sequencing has unveiled an unprecedented discovery of a plethora of long noncoding RNAs (lncRNAs). Despite the lack of coding capacity, lncRNAs have key roles in gene regulation through interacting with various biomolecules. It is increasingly evident that the dysregulation of lncRNAs is inextricably linked to HCC cancer phenotypes, suggesting that lncRNAs are potential prognostic markers and therapeutic targets. In light of the emerging research in the study of the regulatory roles of lncRNAs in HCC, we discuss the association of lncRNAs with HCC. We link the biological processes influenced by lncRNAs to cancer hallmarks in HCC and describe the associated functional mechanisms. This review sheds light on future research directions, including the potential therapeutic applications of lncRNAs.


Asunto(s)
Biomarcadores de Tumor , Carcinoma Hepatocelular/genética , Susceptibilidad a Enfermedades , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/genética , ARN Largo no Codificante , Animales , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Transformación Celular Neoplásica/genética , Manejo de la Enfermedad , Genes Supresores de Tumor , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Técnicas de Diagnóstico Molecular , Terapia Molecular Dirigida , Oncogenes , Transducción de Señal/efectos de los fármacos
8.
Int J Mol Sci ; 22(6)2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33808791

RESUMEN

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Endometriales/genética , Neoplasias Endometriales/mortalidad , ARN no Traducido/genética , Transformación Celular Neoplásica/genética , Metilación de ADN , Susceptibilidad a Enfermedades , Neoplasias Endometriales/diagnóstico , Epigénesis Genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Pronóstico
9.
Medicine (Baltimore) ; 100(15): e25022, 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33847612

RESUMEN

ABSTRACT: Previous studies showed that microRNA (miR)-449a may function as a tumor suppressor. However, the expression pattern and value of circulating miR-449a in colorectal cancer (CRC) remain unclear. Therefore, the purpose of this study was to measure circulating miR-449a level of CRC patients and evaluate its value for predicting prognosis.Plasma samples of 343 consecutive CRC patients and 162 healthy controls were obtained. Circulating miR-449a levels were measured by using real-time quantitative reverse transcription polymerase chain reactions. All enrolled patients were followed up in a regular interval after surgery. The clinical data and survival outcome of all 343 patients were collected. The correlation between circulating miR-449a level and survival outcomes was analyzed by univariate and multivariate analysis.Circulating miR-449a level in CRC patients was significantly decreased (P < .05) comparing with healthy controls. Low miR-449a was significantly associated with CEA and CA19-9 level (both P < .05). Furthermore, patients with a decreased miR-449a level had a lower 5-years overall survival (OS) rate than those with a high miR-449a (67.4% vs 76.9%, P = .03). Low circulating miR-449a level also been demonstrated as an independent risk factor for CRC in multivariate COX analysis (HR, 2.56; 95%CI: 1.15-8.63; P < .05).Circulating miR-449a was significantly decreased in CRC patients and closely related to poor prognosis, suggesting that miR-449a might can be used as a useful diagnostic and prognostic marker for CRC.


Asunto(s)
Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/mortalidad , MicroARNs/sangre , Factores de Edad , Anciano , Biomarcadores de Tumor , Antígeno Carcinoembrionario/sangre , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Factores Sexuales , Carga Tumoral
10.
Medicine (Baltimore) ; 100(15): e25332, 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33847632

RESUMEN

BACKGROUND: A lot of research evidence shows that exosomes play an indelible role in the prognosis of lung cancer, but there are many disputes. Therefore, we conduct a meta-analysis to further demonstrate. METHODS: A literature retrieval was performed through a search of PubMed, Embase, Web of Science, Cochrane, CKNI, Wanfang, and other databases to locate documents from the literature that satisfied the inclusion criteria. There were four outcome indicators: overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS). Subgroup analysis was conducted according to sample size, country, detection method, analysis method, and pathological type. Stata 14.0 software was used to evaluate the prognostic value of exosomes in lung cancer. RESULTS: A total of 2456 patients with lung cancer from 29 studies in 16 articles were included. The expression level of exosomes was closely associated with the OS and DFS of patients, although no statistical difference was observed between exosomes and DSS or PFS. Eighteen studies with 2,110 patients were evaluated to examine the prognostic value of exosomes in lung cancer by exploring the association between exosomes and OS. The results showed that exosomes were strongly associated with worse OS, and the combined hazard ratio (HR) was 2.01 (95% confidence interval [CI]: 1.70-2.39, P = .000). Six studies investigated the association between exosomes and DFS, and showed a pooled HR of 2.48 (95% CI: 1.75-3.53, P = .000). CONCLUSION: Our analysis indicated that the expression level of exosomes was closely associated with the OS and DFS of patients with lung cancer, suggesting that exosomes are associated with poor prognosis of lung cancer. Exosomes may be a new biomarker for the prognosis of lung cancer, although a large number of prospective studies are still needed to support this.


Asunto(s)
Exosomas/metabolismo , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Biomarcadores de Tumor , Humanos , Pronóstico , Análisis de Supervivencia
11.
Medicine (Baltimore) ; 100(15): e25374, 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33847635

RESUMEN

ABSTRACT: The pathogenesis of hepatocellular carcinoma (HCC) can be divided into viral infection (VIR) and nonviral (NVIR) infection. Two types of HCC performed different tumor immune microenvironment (TIME) which directly affected prognosis of HCC. This study aimed to identify an effective 2 types of HCC prognostic gene signature that related to immune TIME.The differential expression genes (DEGs) were analyzed by Limma R package from the Cancer Genome Atlas. Immune related genes getting from IMMport database were matched to DEGs for testing prognosis. Prognostic index (PI) consisted of prognostic immune related genes was calculated in different types of HCC by COX regression and the correlation with the abundance of immune infiltrates, including 6 type cells, via gene modules. Tumor immune estimation resource database was applied to analyze TIME. Finally, the correlations between PI of DEGs and TIICs were analyzed by the Spearman method.Results showed that PI consisted of 11 messenger RNAs in VIR and 12 messenger RNAs in NVIR groups. The PI related to HCC prognosis has different correlations with immune infiltrating cells in VIR and NVIR groups. The PI value of DEGs has significant correlations with neutrophils (R = 0.22, P-value = .029) and dendritic (R = 0.21, P-value = .036) infiltration levels in VIR group. However, in NVIR group, the result showed there were no significant correlations between PI and other 5 type cell infiltration levels (P-value > .05).The 11-gene signature in VIR and 12-gene signature in NVIR group selected based on data from the Cancer Genome Atlas database had a different correlation with immune infiltrating cells of HCC patients.


Asunto(s)
Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/genética , Hepatitis/complicaciones , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/genética , Microambiente Tumoral/genética , Biomarcadores de Tumor , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Hepatitis/epidemiología , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/biosíntesis , Microambiente Tumoral/inmunología
12.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(3): 439-446, 2021 Mar 25.
Artículo en Chino | MEDLINE | ID: mdl-33849837

RESUMEN

OBJECTIVE: To assess the value of the combination of multiple proteins in predicting the prognosis of colorectal cancer (CRC) through bioinformatics analysis. OBJECTIVE: The protein expression and clinical data were downloaded from TCPA database. Perl and R were used to screen the prognostic-related proteins, and through Cox analysis, the proteins that served as independent prognostic factors of CRC were identified to build the prediction model. Survival analyses were conducted for each of the proteins included in the prediction model and the risk score of the model, and risk curves was drawn for the risk score and the patients' survival status to verify the performance of the model. Independent prognosis analysis and ROC analysis were used to assess the value and advantages of the model in prognosis prediction. The interactions between the proteins included in the model and the differential expressions of the key genes related with the proteins were analyzed. OBJECTIVE: Six proteins were screened for model construction. Compared with a single gene, the model showed much greater prognostic value for CRC. Independent prognostic analysis showed that the risk score of the prediction model was significantly related with the prognosis (P < 0.001), and the model could be used as an independent risk factor for prognostic assessment of the patients. ROC analysis showed that the model had good specificity and sensitivity for prognostic prediction (AUC=0.734). Protein interactions showed that BID, SLC1A5 and SRC_pY527 were significantly correlated with other proteins (P < 0.001), and SLC1A5 and SRC_pY527 had the most significant interactions with other proteins (P < 0.001). Except for those of INPP4B, the key genes related with the proteins in the prediction model had significant differential expressions at the mRNA level in CRC (P < 0.05). OBJECTIVE: The prediction model constructed based on 6 proteins has good prognostic value for CRC. The proteins SLC1A5 and SRC_pY527 play key roles in the prognosis of CRC, and SRC_pY527 may regulate the occurrence and progression of CRC through the SRC/AKT/MAPK signal axis and thus may serve as a new therapeutic target of CRC.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Colorrectales , Sistema de Transporte de Aminoácidos ASC , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Antígenos de Histocompatibilidad Menor , Pronóstico , Análisis de Supervivencia
13.
Int J Mol Sci ; 22(5)2021 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-33803085

RESUMEN

Exosomes are extracellular vesicles, enriched in biomolecular cargo consisting of nucleic acids, proteins, and lipids, which take part in intercellular communication and play a crucial role in both physiologic functions and oncogenesis. Bladder cancer is the most common urinary malignancy and its incidence is steadily rising in developed countries. Despite the high five-year survival in patients diagnosed at early disease stage, survival substantially drops in patients with muscle-invasive or metastatic disease. Therefore, early detection of primary disease as well as recurrence is of paramount importance. The role that exosomal biomarkers could play in bladder cancer patient diagnosis and surveillance, as well as their potential therapeutic applications, has not been extensively studied in this malignancy. In the present review, we summarize all relevant data obtained so far from cell lines, animal models, and patient biofluids and tissues. Current literature suggests that urine is a rich source of extracellular vesicle-derived biomarkers, compared with blood and bladder tissue samples, with potential applications in bladder cancer management. Further studies improving sample collection procedures and optimizing purification and analytical methods should augment bladder cancer diagnostic, prognostic, and therapeutic input of extracellular vesicles biomarkers in the future.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Exosomas/metabolismo , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/terapia , Exosomas/patología , Humanos , Metástasis de la Neoplasia , Neoplasias de la Vejiga Urinaria/patología
14.
Int J Mol Sci ; 22(5)2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33804393

RESUMEN

We recently discovered a novel nargenicin A1 analog, 23-demethyl 8,13-deoxynargenicin (compound 9), with potential anti-cancer and anti-angiogenic activities against human gastric adenocarcinoma (AGS) cells. To identify the key molecular targets of compound 9, that are responsible for its biological activities, the changes in proteome expression in AGS cells following compound 9 treatment were analyzed using two-dimensional gel electrophoresis (2-DE), followed by MALDI/TOF/MS. Analyses using chemical proteomics and western blotting revealed that compound 9 treatment significantly suppressed the expression of cyclophilin A (CypA), a member of the immunophilin family. Furthermore, compound 9 downregulated CD147-mediated mitogen-activated protein kinase (MAPK) signaling pathway, including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) by inhibiting the expression of CD147, the cellular receptor of CypA. Notably, the responses of AGS cells to CypA knockdown were significantly correlated with the anticancer and antiangiogenic effects of compound 9. CypA siRNAs reduced the expression of CD147 and phosphorylation of JNK and ERK1/2. In addition, the suppressive effects of CypA siRNAs on proliferation, migration, invasion, and angiogenesis induction of AGS cells were associated with G2/M cell cycle arrest, caspase-mediated apoptosis, inhibition of MMP-9 and MMP-2 expression, inactivation of PI3K/AKT/mTOR pathway, and inhibition of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression. The specific interaction between compound 9 and CypA was also confirmed using the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) approaches. Moreover, in silico docking analysis revealed that the structure of compound 9 was a good fit for the cyclosporin A binding cavity of CypA. Collectively, these findings provide a novel molecular basis for compound 9-mediated suppression of gastric cancer progression through the targeting of CypA.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Ciclofilina A/metabolismo , Proteoma/análisis , Proteoma/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Apoptosis , Ciclo Celular , Proliferación Celular , Humanos , Lactonas/química , Lactonas/farmacología , Nocardia/metabolismo , Proteoma/metabolismo , Transducción de Señal , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Células Tumorales Cultivadas
15.
Anticancer Res ; 41(4): 2053-2058, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813413

RESUMEN

AIM: To investigate potential associations between selected oncomarkers [carcinoembryonic antigen (CEA), C-terminus of cytokeratin 19 (CYFRA 21-1, CYFRA), and squamous cell carcinoma antigen (SCC)] and outcomes in patients with NSCLC treated with bevacizumab plus chemotherapy. PATIENTS AND METHODS: We retrospectively analysed 105 patients with NSCLC from the Czech TULUNG registry treated at University Hospital in Pilsen with bevacizumab plus chemotherapy. Response to therapy was tested by Fisher's exact test. Survival statistics were evaluated using the Kaplan-Meier method and Cox analysis. RESULTS: Only normal values of CYFRA (not CEA or SCC) were associated with significantly better overall and progression-free survival in univariate analysis. We also observed a trend for a better disease control rate in patients with normal levels of CYFRA. In a multivariate Cox model, only CYFRA was associated with significantly better overall but not progression-free survival. CONCLUSION: In our retrospective study, we point out the possibility of using CYFRA as a prognostic marker in patients with NSCLC treated with chemotherapy plus bevacizumab.


Asunto(s)
Antígenos de Neoplasias/fisiología , Antineoplásicos/uso terapéutico , Bevacizumab/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Queratina-19/fisiología , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Antígenos de Neoplasias/análisis , Antígenos de Neoplasias/sangre , Bevacizumab/efectos adversos , Biomarcadores Farmacológicos/análisis , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/fisiología , Antígeno Carcinoembrionario/análisis , Antígeno Carcinoembrionario/sangre , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Progresión de la Enfermedad , Femenino , Humanos , Queratina-19/análisis , Queratina-19/sangre , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Serpinas/análisis , Serpinas/sangre , Resultado del Tratamiento
16.
Pol Merkur Lekarski ; 49(290): 103-107, 2021 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-33895754

RESUMEN

MicroRNAs (miRNA) are short, single stranded, non-coding RNAs that play an important role in controlling gene expression at the posttranscriptional stage. There is no bladder cancer marker that has been approved as an alternative for diagnostic cystoscopy and urine cytology so far, thus research for alternative, more sensitive, and less invasive methods of bladder cancer detection are being made. AIM: The aim of the study was to compare the relative expression levels of miRNAs in patients with bladder cancer. MATERIALS AND METHODS: Urine and serum samples were collected from patients with the diagnosis of bladder cancer (NMIBC 71%, MIBC 29%). We assessed expression of 4 miRNAs (106b-3p, 130b-3, 145- 3p and 199a-5p) using real-time PCR and double delta (ΔΔCt) method. The analysis was performed with the Mann-Whitney U test. RESULTS: miRNA 145-3p was significantly underexpressed in urine (p=0,0111) compared with control group, whereas in serum we did not find relevant differences between groups (p=0,0903). Overexpression was observed for miRNA 199a-5p tested in urine (p=0,0262) and for miRNA 106b-3p for both urine and serum (p=0,0262 and p=0,0149 respectively). For miR-130b-3 we did not find statistically significant differences neither for urine (p=0,6335) nor serum (p=0,2443). CONCLUSIONS: A correlation between the relative levels of expression for miRNA 106b-3p, 199a-5p and miRNA 145-3p was detected. We also observed differences between the results obtained for urine and serum. In the context of urinary cancers diagnosis urine seems to be more useful material than serum. We plan to continue our studies assessing expression levels of miRNA 106b-3 and miRNA 145-3p.


Asunto(s)
MicroARNs , Neoplasias de la Vejiga Urinaria , Biomarcadores , Biomarcadores de Tumor/genética , Humanos , MicroARNs/genética , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/genética
17.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-33800786

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is known as a highly aggressive malignant disease. Prognosis for patients is notoriously poor, despite improvements in surgical techniques and new (neo)adjuvant chemotherapy regimens. Early detection of PDAC may increase the overall survival. It is furthermore foreseen that precision medicine will provide improved prognostic stratification and prediction of therapeutic response. In this review, omics-based discovery efforts are presented that aim for novel diagnostic and prognostic biomarkers of PDAC. For this purpose, we systematically evaluated the literature published between 1999 and 2020 with a focus on protein- and protein-glycosylation biomarkers in pancreatic cancer patients. Besides genomic and transcriptomic approaches, mass spectrometry (MS)-based proteomics and glycomics of blood- and tissue-derived samples from PDAC patients have yielded new candidates with biomarker potential. However, for reasons discussed in this review, the validation and clinical translation of these candidate markers has not been successful. Consequently, there has been a change of mindset from initial efforts to identify new unimarkers into the current hypothesis that a combination of biomarkers better suits a diagnostic or prognostic panel. With continuing development of current research methods and available techniques combined with careful study designs, new biomarkers could contribute to improved detection, prognosis, and prediction of pancreatic cancer.


Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma Ductal Pancreático/diagnóstico , Glicómica/métodos , Glicoproteínas/análisis , Espectrometría de Masas/métodos , Proteínas de Neoplasias/análisis , Neoplasias Pancreáticas/diagnóstico , Proteómica/métodos , Líquidos Corporales/química , Carcinoma Ductal Pancreático/química , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidad , Toma de Decisiones Clínicas , Diagnóstico Diferencial , Detección Precoz del Cáncer , Humanos , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/epidemiología , Síndromes Neoplásicos Hereditarios/genética , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidad , Pancreatitis Crónica/diagnóstico , Lesiones Precancerosas/diagnóstico , Medicina de Precisión , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Factores de Riesgo
18.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-33800799

RESUMEN

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.


Asunto(s)
Biopsia Líquida , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/sangre , Vías Clínicas , ADN de Neoplasias/química , Manejo de la Enfermedad , Femenino , Humanos , Masculino , MicroARNs/análisis , Proteínas de Neoplasias/análisis , Neoplasias de Células Germinales y Embrionarias/sangre , Neoplasias de Células Germinales y Embrionarias/química , Neoplasias de Células Germinales y Embrionarias/patología , Células Neoplásicas Circulantes , Neoplasias Ováricas/sangre , Neoplasias Ováricas/química , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patología , ARN Neoplásico/análisis , Neoplasias Testiculares/sangre , Neoplasias Testiculares/química , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patología
19.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33803955

RESUMEN

MicroRNAs (miRs) are non-coding master regulators of transcriptome that could act as tumor suppressors (TSs) or oncogenes (oncomiRs). We aimed to systematically investigate the relevance of miRs as prognostic biomarkers in primary glioblastoma multiforme (GBM) treated with postoperative radio(chemo)therapy (PORT). For hypothesis generation, tumor miR expression by Agilent 8x15K human microRNA microarrays and survival data from 482 GBM patients of The Cancer Genome Atlas (TCGA cohort) were analyzed using Cox-PH models. Expression of candidate miRs with prognostic relevance (miR-221/222; miR-17-5p, miR-18a, miR-19b) was validated by qRT-PCR using Taqman technology on an independent validation cohort of GBM patients (n = 109) treated at Heidelberg University Hospital (HD cohort). In TCGA, 50 miRs showed significant association with survival. Among the top ranked prognostic miRs were members of the two miR families miR-221/222 and miR-17-92. Loss of miR-221/222 was correlated with improved prognosis in both cohorts (TCGA, HD) and was an independent prognostic marker in a multivariate analysis considering demographic characteristics (age, sex, Karnofsky performance index (KPI)), molecular markers (O-6-methylguanine-DNA methyltransferase (MGMT) methylation, IDH mutation status) and PORT as co-variables. The prognostic value of miR-17-92 family members was ambiguous and in part contradictory by direct comparison of the two cohorts, thus warranting further validation in larger prospective trials.


Asunto(s)
Glioblastoma/radioterapia , MicroARNs/genética , ARN Largo no Codificante/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Glioblastoma/genética , Glioblastoma/patología , Glioblastoma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Regiones Promotoras Genéticas/genética , Análisis de Matrices Tisulares , Transcriptoma/genética
20.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33807045

RESUMEN

Breast cancer is very heterogenous and the most common gynaecological cancer, with various factors affecting its development. While its impact on human lives and national health budgets is still rising in almost all global areas, many molecular mechanisms affecting its onset and development remain unclear. Conventional treatments still prove inadequate in some aspects, and appropriate molecular therapeutic targets are required for improved outcomes. Recent scientific interest has therefore focused on the non-coding RNAs roles in tumour development and their potential as therapeutic targets. These RNAs comprise the majority of the human transcript and their broad action mechanisms range from gene silencing to chromatin remodelling. Many non-coding RNAs also have altered expression in breast cancer cell lines and tissues, and this is often connected with increased proliferation, a degraded extracellular environment, and higher endothelial to mesenchymal transition. Herein, we summarise the known abnormalities in the function and expression of long non-coding RNAs, Piwi interacting RNAs, small nucleolar RNAs and small nuclear RNAs in breast cancer, and how these abnormalities affect the development of this deadly disease. Finally, the use of RNA interference to suppress breast cancer growth is summarised.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica , ARN no Traducido/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Humanos , Biopsia Líquida/métodos , Interferencia de ARN , ARN no Traducido/química
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