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1.
Medicine (Baltimore) ; 100(14): e24118, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33832059

RESUMEN

ABSTRACT: Genetic alterations are vital to the progression of osteosarcoma carcinoma. The present study investigated a panel of gene signatures that could evaluate prognosis in osteosarcoma based on data from the Therapeutically Applicable Research To Generate Effective Treatments initiative. Osteosarcoma messenger RNA (mRNA) profiles and clinical data were downloaded from the therapeutically applicable research to generate effective treatments database. Patients with osteosarcoma were divided into two groups based on findings at diagnosis: with and without metastasis. Differentially expressed mRNAs were compared and analyzed between groups. Univariate and multivariate Cox regression analyses identified a set of eight mRNAs with the ability to classify patients into high-risk and low-risk groups with significantly different overall survival times. Further analysis indicated that the eight-mRNA signature was an independent prognostic factor after adjusting for other clinical factors. Receiver operating characteristic curve analysis demonstrated a good performance of the eight-mRNA signature. Further, the biological processes and signaling pathways of the eight-mRNA signature were reviewed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes resources. Finally, the results of the TCGA analysis were verified by other cohorts from Gene Expression Omnibus database. The identification of an eight-mRNA signature not only provides a prognostic biomarker of osteosarcoma but also offers the potential of novel therapeutic targets for its treatment.


Asunto(s)
Neoplasias Óseas/genética , Osteosarcoma/genética , ARN Mensajero/metabolismo , Adolescente , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/mortalidad , Niño , Bases de Datos Factuales , Femenino , Humanos , Masculino , Osteosarcoma/mortalidad , Curva ROC , Análisis de Secuencia de ARN , Transcriptoma
2.
Medicine (Baltimore) ; 100(14): e25364, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33832117

RESUMEN

RATIONALE: Although dysgerminomas are relatively uncommon among all ovarian neoplasms, representing for only about 2%, they account for 32.8 percent of malignant ovarian germ cell tumors. Their association with pregnancy is extremely rare; due to the low frequency of occurrence, there are few recommendations regarding pregnancy management; therefore, it is important to discuss and summarize the treatment strategy. PATIENT CONCERNS: We present the case of a 25 years patient, gestation 1, para 1, who was hospitalized in the clinic at 38/39 weeks of gestation at the beginning of labor. Following the ultrasound examination, a hypoechogenic lesion on the uterine fundus was found, suggestive of subterranean fibroid. After caesarean section, right adnexectomy was performed; the histopathological examination revealed, unexpectedly, the diagnosis of dysgerminoma. DIAGNOSES: Dysgerminoma as associated with pregnancy. INTERVENTIONS: Birth by Caesarean section and right adnexectomy. No other medical complications occurred. OUTCOMES: The histopathological and immunohistochemical examinations were consistent with the pure dysgerminoma. Oncology was staged AI, with the monitoring of markers and abdominal and pelvic magnetic resonance imaging at 3, 6, 9, and 12 months. LESSONS: Dysgerminoma is the most common ovarian malignancy associated with pregnancy with a good fetal maternal outcome. If these tumors are discovered accidentally during caesarean section, tumor markers and magnetic resonance imaging scanning should be done postoperatively to plan optimal treatment.


Asunto(s)
Disgerminoma/diagnóstico , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Ováricas/patología , Adulto , Cuidados Posteriores , Biomarcadores de Tumor/metabolismo , Cesárea/métodos , Disgerminoma/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Neoplasias de Células Germinales y Embrionarias/cirugía , Neoplasias Ováricas/cirugía , Embarazo , Complicaciones Neoplásicas del Embarazo/patología , Resultado del Tratamiento , Ultrasonografía/métodos
3.
Int J Mol Sci ; 22(6)2021 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-33803640

RESUMEN

The LATS1 kinase has been described as a tumor suppressor in various cancers. However, its role in melanoma has not been fully elucidated. There are several processes involved in tumorigenesis, including melanin production. Melanin content positively correlates with the level of reactive oxygen species (ROS) inside the cell. Accordingly, the purpose of the study was to assess the role of LATS1 in melanogenesis and oxidative stress and its influence on tumor growth. We have knocked down LATS1 in primary melanocytes and melanoma cells and found that its expression is crucial for melanin synthesis, ROS production, and oxidative stress response. We showed that LATS1 ablation significantly decreased the melanogenesis markers' expression and melanin synthesis in melanocyte and melanoma cell lines. Moreover, silencing LATS1 resulted in enhanced oxidative stress. Reduced melanin content in LATS1 knocked down tumors was associated with increased tumor growth, pointing to melanin's protective role in this process. The study demonstrated that LATS1 is highly engaged in melanogenesis and oxidative stress control and affects melanoma growth. Our results may find the implications in the diagnosis and treatment of pigmentation disorders, including melanoma.


Asunto(s)
Melaninas/biosíntesis , Melanoma/patología , Estrés Oxidativo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Animales , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Cinética , Melanocitos/metabolismo , Melanoma/genética , Ratones Desnudos , Especies Reactivas de Oxígeno/metabolismo , Estrés Fisiológico , Transactivadores/metabolismo , Factores de Transcripción/metabolismo , Hipoxia Tumoral/genética
4.
Int J Mol Sci ; 22(6)2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33809749

RESUMEN

Metastatic castration-resistant prostate cancer (mCRPC) represents a condition of progressive disease in spite of androgen deprivation therapy (ADT), with a broad spectrum of manifestations ranging from no symptoms to severe debilitation due to bone or visceral metastatization. The management of mCRPC has been profoundly modified by introducing novel therapeutic tools such as antiandrogen drugs (i.e., abiraterone acetate and enzalutamide), immunotherapy through sipuleucel-T, and targeted alpha therapy (TAT). This variety of approaches calls for unmet need of biomarkers suitable for patients' pre-treatment selection and prognostic stratification. In this scenario, imaging with positron emission computed tomography (PET/CT) presents great and still unexplored potential to detect specific molecular and metabolic signatures, some of whom, such as the prostate specific membrane antigen (PSMA), can also be exploited as therapeutic targets, thus combining diagnosis and therapy in the so-called "theranostic" approach. In this review, we performed a web-based and desktop literature research to investigate the prognostic and theranostic potential of several PET imaging probes, such as 18F-FDG, 18F-choline and 68Ga-PSMA-11, also covering the emerging tracers still in a pre-clinical phase (e.g., PARP-inhibitors' analogs and the radioligands binding to gastrin releasing peptide receptors/GRPR), highlighting their potential for defining personalized care pathways in mCRPC.


Asunto(s)
Tomografía de Emisión de Positrones , Medicina de Precisión , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico , Neoplasias de la Próstata Resistentes a la Castración/terapia , Biomarcadores de Tumor/metabolismo , Humanos , Masculino , Metástasis de la Neoplasia , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/patología
5.
Nat Commun ; 12(1): 2048, 2021 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-33824345

RESUMEN

Loss of TP53 and RB1 in treatment-naïve small cell lung cancer (SCLC) suggests selective pressure to inactivate cell death pathways prior to therapy. Yet, which of these pathways remain available in treatment-naïve SCLC is unknown. Here, through systemic analysis of cell death pathway availability in treatment-naïve SCLC, we identify non-neuroendocrine (NE) SCLC to be vulnerable to ferroptosis through subtype-specific lipidome remodeling. While NE SCLC is ferroptosis resistant, it acquires selective addiction to the TRX anti-oxidant pathway. In experimental settings of non-NE/NE intratumoral heterogeneity, non-NE or NE populations are selectively depleted by ferroptosis or TRX pathway inhibition, respectively. Preventing subtype plasticity observed under single pathway targeting, combined treatment kills established non-NE and NE tumors in xenografts, genetically engineered mouse models of SCLC and patient-derived cells, and identifies a patient subset with drastically improved overall survival. These findings reveal cell death pathway mining as a means to identify rational combination therapies for SCLC.


Asunto(s)
Ferroptosis , Tumores Neuroendocrinos/patología , Carcinoma Pulmonar de Células Pequeñas/patología , Animales , Antioxidantes/metabolismo , Apoptosis , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Humanos , Metabolismo de los Lípidos , Masculino , Ratones Desnudos , Modelos Biológicos , Necroptosis , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípidos/metabolismo , Pronóstico , Tiorredoxinas/metabolismo
6.
Medicine (Baltimore) ; 100(14): e25415, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33832139

RESUMEN

BACKGROUND: Circular RNAs (circRNAs) regulate multiple pathways during lung cancer pathogenesis. Apart from functional significance, many circRNAs have been shown to be associated with clinicopathological characteristics and predict lung cancer prognosis. Our aim is to summarize the expanding knowledge of clinical roles of circRNAs in lung cancer. METHODS: A thorough search of literature was conducted to identify articles about the correlation between circRNA expression and its prognostic and clinicopathological values. Biological mechanisms were summarized. RESULTS: This study included 35 original articles and 32 circRNAs with prognostic roles for lung cancer. Increased expression of 25 circRNAs and decreased expression of 7 circRNAs predicted poor prognosis. For non-small cell lung cancer, changes of circRNAs were correlated with tumor size, lymph node metastasis, distant metastasis, tumor node metastasis (TNM) stage, and differentiation, indicating the major function of circRNAs is to promote lung cancer invasion and migration. Particularly, meta-analysis of ciRS-7, hsa_circ_0020123, hsa_circ_0067934 showed increase of the 3 circRNAs was associated with positive lymph node metastasis. Increase of ciRS-7 and hsa_circ_0067934 was also related with advanced TNM stage. The biological effects depend on the general function of circRNA as microRNA sponge. CONCLUSIONS: CircRNAs have the potential to function as prognostic markers and are associated with lung cancer progression and metastasis.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Pulmonares/diagnóstico , ARN Circular/metabolismo , Progresión de la Enfermedad , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Invasividad Neoplásica , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico
7.
Medicine (Baltimore) ; 100(14): e25454, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33832153

RESUMEN

BACKGROUND: Numbers of studies have reported that the expression of aldo-keto reductase family 1 member B10 (AKR1B10) is abnormal in digestive system cancers, and could be used as a prognostic biomarker. However, the results are argued. Therefore, we conduct a meta-analysis to comprehensively evaluate the prognostic value of high AKR1B10 expression for overall survival (OS), disease specific survival (DSS), and disease-free survival/recurrence-free survival (DFS/PFS) in digestive system cancers. METHODS: Hazard ratios (HRs) with its 95% confidence intervals (CIs) were calculated to assess the prognostic value of AKR1B10 by using the random effects model. The STATA version 12.0 software were used to perform all the analyses. RESULTS: Eleven articles including 1428 patients involved in this meta-analysis. The pooled analysis suggested that high AKR1B10 expression was not associated with OS (HR: 1.18; 95% CI: 0.69-2.00) and DFS/PFS (HR: 1.08, 95% CI: 0.67-1.76) in digestive system cancers. However, Further analysis revealed that high AKR1B10 expression indicated poor OS in oral squamous cell carcinomas (OSCC) (HR: 2.92, 95% CI: 1.86-4.58) and favorable DSS in hepatocellular carcinoma (HCC) (HR: 0.71, 95% CI: 0.52-0.97). CONCLUSIONS: The prognostic value of high AKR1B10 expression varied in different types of digestive system cancers. Further studies exploring the prognostic role of AKR1B10 in digestive system cancers are needed.


Asunto(s)
Aldo-Ceto Reductasas/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias del Sistema Digestivo/diagnóstico , Neoplasias del Sistema Digestivo/mortalidad , Neoplasias del Sistema Digestivo/metabolismo , Neoplasias del Sistema Digestivo/terapia , Humanos , Pronóstico , Análisis de Supervivencia
8.
Anticancer Res ; 41(4): 2117-2122, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813422

RESUMEN

BACKGROUND/AIM: Stanniocalcin2 (STC2) is associated with proliferation, invasion, and metastasis in various cancers. We examined the clinical significance of STC2 mRNA expression in patients with colorectal cancer (CRC). PATIENTS AND METHODS: Relative expression levels of STC2 mRNA in CRC tissues and corresponding normal mucosa obtained from 202 patients were measured using quantitative real-time reverse transcriptase-polymerase chain reaction. RESULTS: Expression of STC2 mRNA was higher in the cancer tissue than in the adjacent normal mucosa. STC2 mRNA expression in cancer tissues was associated with tumour size, liver metastasis, venous invasion, and lymph node metastasis. High expression of STC2 mRNA was significantly associated with poorer postoperative survival (p=0.0003). Multivariate analysis showed that high expression of STC2 mRNA was an independent predictor of postoperative survival. CONCLUSION: High expression of STC2 mRNA in CRC tissue may be a useful prognostic marker in patients with CRC.


Asunto(s)
Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/diagnóstico , Glicoproteínas/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Anciano , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Femenino , Regulación Neoplásica de la Expresión Génica , Glicoproteínas/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Supervivencia , Resultado del Tratamiento
9.
Anticancer Res ; 41(4): 2133-2140, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813424

RESUMEN

BACKGROUND/AIM: Tumor-infiltrating lymphocytes (TILs) are considered a prognostic marker for triple-negative breast cancer (TNBC). Immune checkpoint inhibitor (ICI)-based treatments are more effective for tumors with PD-L1-positive TILs, suggesting crucial roles of TILs in the local tumor immunity. However, factors attracting TILs are still largely unknown. Focusing on tumor antigenicity, we examined TNBC samples to identify the characteristics of TIL-high tumors. PATIENTS AND METHODS: Nine treatment-naïve TNBCs (TIL-high: five, TIL-low: four) were subjected to next-generation sequencing (NGS). Loss of heterozygosity (LOH) of PTEN was also analyzed. RESULTS: A variety of copy number variations were observed, and no genes differed significantly between TIL-high and -low groups. However, PTEN loss was more frequently observed in the TIL-high group: 60% compared to 25% in TIL-low tumors. NGS correlated well with LOH analysis in identifying PTEN loss. All three tumors with PTEN loss in the TIL-high group showed high PD-L1. All nine samples were microsatellite-stable. CONCLUSION: Frequent PTEN loss and high expression of PD-L1 in TIL-high TNBC suggest that PTEN mutation may be a biomarker for ICIs.


Asunto(s)
Biomarcadores de Tumor/genética , Linfocitos Infiltrantes de Tumor/metabolismo , Neoplasias de la Mama Triple Negativas/diagnóstico , Neoplasias de la Mama Triple Negativas/genética , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores Farmacológicos/análisis , Biomarcadores Farmacológicos/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Variaciones en el Número de Copia de ADN , Análisis Mutacional de ADN/métodos , Regulación Neoplásica de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Pérdida de Heterocigocidad , Recuento de Linfocitos , Linfocitos/metabolismo , Linfocitos/patología , Linfocitos Infiltrantes de Tumor/patología , Persona de Mediana Edad , Mutación , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Polimorfismo de Nucleótido Simple , Pronóstico , Transcriptoma , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo
10.
Anticancer Res ; 41(4): 2147-2155, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813426

RESUMEN

BACKGROUND/AIM: Inflammation-based prognostic scores are proven prognostic biomarkers in various cancers. This study aimed to identify a useful prognostic score for patients with biliary tract cancer (BTC) after surgical resection. PATIENTS AND METHODS: This retrospective study recruited 115 patients with BTC during 2010-2020. The relationship between clinicopathological variables, including various prognostic scores and overall survival (OS), was investigated using univariate and multivariate analyses. RESULTS: BTC included 58 cholangiocarcinoma, 29 gallbladder carcinoma, 16 ampullary carcinoma, and 12 perihilar cholangiocarcinoma cases. A significant difference was detected in OS of patients with a Japanese modified Glasgow prognostic score (JmGPS) 0 (n=62) and JmGPS 1 or 2 (high JmGPS) (n=53). In the multivariate analysis, tumour differentiation (p=0.014) and a high JmGPS (p=0.047) were independent prognostic factors. CONCLUSION: The high JmGPS was an independent prognostic predictor after surgical resection and was superior to other prognostic scores.


Asunto(s)
Neoplasias del Sistema Biliar/diagnóstico , Neoplasias del Sistema Biliar/cirugía , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/cirugía , Inflamación/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática/metabolismo , Ampolla Hepatopancreática/patología , Ampolla Hepatopancreática/cirugía , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos/metabolismo , Conductos Biliares Intrahepáticos/patología , Conductos Biliares Intrahepáticos/cirugía , Neoplasias del Sistema Biliar/metabolismo , Neoplasias del Sistema Biliar/mortalidad , Biomarcadores de Tumor/metabolismo , Proteína C-Reactiva/metabolismo , Colangiocarcinoma/metabolismo , Colangiocarcinoma/mortalidad , Neoplasias del Conducto Colédoco/diagnóstico , Neoplasias del Conducto Colédoco/metabolismo , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/cirugía , Femenino , Neoplasias de la Vesícula Biliar/diagnóstico , Neoplasias de la Vesícula Biliar/metabolismo , Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Inflamación/metabolismo , Japón/epidemiología , Tumor de Klatskin/diagnóstico , Tumor de Klatskin/metabolismo , Tumor de Klatskin/mortalidad , Tumor de Klatskin/cirugía , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Pronóstico , Proyectos de Investigación , Estudios Retrospectivos , Sensibilidad y Especificidad , Análisis de Supervivencia , Resultado del Tratamiento
11.
Anticancer Res ; 41(4): 2177-2182, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813430

RESUMEN

BACKGROUND/AIM: To investigate the impact of PDZ-binding kinase (PBK) on the clinical outcome of patients with oral squamous cell carcinoma (OSCC) who received radiotherapy. PATIENTS AND METHODS: PBK immunoreactivity of cancer specimens obtained from 179 patients with primary OSCC was analyzed by immunohistochemistry. RESULTS: High PBK expression in tumor cells tended to be associated with advanced N-stage. The 5-year survival rate was greater for patients with high total PBK expression than in those with low PBK expression. After adjustment, high PBK remained associated with a favorable outcome. In subgroups according to tumor stage, the prognostic role was significant in patients with stage III/IV rather than those with stage I/II disease. CONCLUSION: We suggest that PBK expression should be used as an independent prognostic marker for patients with OSCC treated with radiotherapy, especially for those with advanced-stage disease.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/radioterapia , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/radioterapia , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Inmunohistoquímica , Estilo de Vida , Masculino , Persona de Mediana Edad , Quinasas de Proteína Quinasa Activadas por Mitógenos/fisiología , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Análisis de Supervivencia , Taiwán/epidemiología
12.
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
13.
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
14.
Int J Mol Sci ; 22(6)2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33802234

RESUMEN

Recent advances in sequencing and biotechnological methodologies have led to the generation of large volumes of molecular data of different omics layers, such as genomics, transcriptomics, proteomics and metabolomics. Integration of these data with clinical information provides new opportunities to discover how perturbations in biological processes lead to disease. Using data-driven approaches for the integration and interpretation of multi-omics data could stably identify links between structural and functional information and propose causal molecular networks with potential impact on cancer pathophysiology. This knowledge can then be used to improve disease diagnosis, prognosis, prevention, and therapy. This review will summarize and categorize the most current computational methodologies and tools for integration of distinct molecular layers in the context of translational cancer research and personalized therapy. Additionally, the bioinformatics tools Multi-Omics Factor Analysis (MOFA) and netDX will be tested using omics data from public cancer resources, to assess their overall robustness, provide reproducible workflows for gaining biological knowledge from multi-omics data, and to comprehensively understand the significantly perturbed biological entities in distinct cancer types. We show that the performed supervised and unsupervised analyses result in meaningful and novel findings.


Asunto(s)
Biomarcadores de Tumor , Biología Computacional , Genómica , Metabolómica , Neoplasias , Proteómica , Investigación en Medicina Traslacional , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/terapia
15.
Int J Mol Sci ; 22(5)2021 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-33802597

RESUMEN

Heat shock protein 90 (HSP90) plays an essential role in lung adenocarcinoma, acting as a key chaperone involved in the correct functioning of numerous highly relevant protein drivers of this disease. To this end, HSP90 inhibitors have emerged as promising therapeutic strategies, even though responses to them have been limited to date. Given the need to maximize treatment efficacy, the objective of this study was to use isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic techniques to identify proteins in human lung adenocarcinoma cell lines whose basal abundances were correlated with response to HSP90 inhibitors (geldanamycin and radicicol derivatives). From the protein profiles identified according to response, the relationship between lactate dehydrogenase B (LDHB) and DNA topoisomerase 1 (TOP1) with respect to sensitivity and resistance, respectively, to geldanamycin derivatives is noteworthy. Likewise, rhotekin (RTKN) and decaprenyl diphosphate synthase subunit 2 (PDSS2) were correlated with sensitivity and resistance to radicicol derivatives. We also identified a relationship between resistance to HSP90 inhibition and the p53 pathway by glucose deprivation. In contrast, arginine biosynthesis was correlated with sensitivity to HSP90 inhibitors. Further study of these outcomes could enable the development of strategies to improve the clinical efficacy of HSP90 inhibition in patients with lung adenocarcinoma.


Asunto(s)
Adenocarcinoma del Pulmón/metabolismo , Biomarcadores de Tumor/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Neoplasias Pulmonares/metabolismo , Células A549 , Adenocarcinoma del Pulmón/tratamiento farmacológico , Antineoplásicos/farmacología , Benzoquinonas/farmacología , Línea Celular Tumoral , Humanos , Lactamas Macrocíclicas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Chaperonas Moleculares/metabolismo , Proteómica/métodos
16.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-33802702

RESUMEN

Our previous study demonstrated that the glutathione S-transferase Mu 5 (GSTM5) gene is highly CpG-methylated in bladder cancer cells and that demethylation by 5-aza-dC activates GSTM5 gene expression. The aim of the present study was to investigate the role of GSTM5 in bladder cancer. The levels of GSTM5 gene expression and DNA methylation were analyzed in patients with bladder cancer, and functional studies of GSTM5 were conducted using GSTM5 overexpression in cultured bladder cancer cells. Clinical analysis revealed that the GSTM5 mRNA expression was lower in bladder cancer tissues than in normal tissues and that the level of GSTM5 DNA methylation was higher in bladder cancer tissues than in normal urine pellets. Overexpression of GSTM5 decreased cell proliferation, migration and colony formation capacity. Glutathione (GSH) assay results indicated that cellular GSH concentration was decreased by GSTM5 expression and that GSH supplementation reversed the decrease in proliferation and migration of cells overexpressing GSTM5. By contrast, a GSH synthesis inhibitor significantly decreased 5637 cell GSH levels, survival and migration. Furthermore, GSTM5 overexpression inhibited the adhesion of cells to the extracellular matrix protein fibronectin. To elucidate the effect of GSTM5 on anticancer drugs used to treat bladder cancer, cellular viability was compared between cells with or without GSTM5 overexpression. GSTM5-overexpressed cells showed no significant change in the cytotoxicity of cisplatin or mitomycin C in 5637, RT4 and BFTC 905 cells. Though a degree of resistance to doxorubicin was noted in 5637 cells overexpressing GSTM5, no such resistance was observed in RT4 and BFTC 905 cells. In summary, GSTM5 plays a tumor suppressor role in bladder cancer cells without significantly affecting chemoresistance to cisplatin and mitomycin C, and the cellular GSH levels highlight a key mechanism underlying the cancer inhibition effect of GSTM5. These findings suggest that low gene expression and high DNA methylation levels of GSTM5 may act as tumor markers for bladder cancer.


Asunto(s)
Antineoplásicos/metabolismo , Biomarcadores de Tumor/metabolismo , Glutatión Transferasa/metabolismo , Neoplasias de la Vejiga Urinaria/enzimología , Adulto , Anciano , Anciano de 80 o más Años , Butionina Sulfoximina/farmacología , Adhesión Celular/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Cisplatino/farmacología , Metilación de ADN/efectos de los fármacos , Metilación de ADN/genética , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Doxorrubicina/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glutatión/metabolismo , Glutatión Transferasa/genética , Humanos , Masculino , Persona de Mediana Edad , Mitomicina/farmacología , Regiones Promotoras Genéticas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Caracteres Sexuales , Neoplasias de la Vejiga Urinaria/genética
17.
Medicine (Baltimore) ; 100(16): e25452, 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33879677

RESUMEN

BACKGROUND: Currently, an increasing number of long noncoding RNAs (LncRNAs) have been reported to be abnormally expressed in human carcinomas and play a vital role in tumourigenesis. Some studies have been carried out to investigate the influence of the expression of LncRNA human urothelial carcinoma associated 1 (UCA1) on prognosis and clinical significance in patients with esophageal cancer, but the results are contradictory and uncertain. A meta-analysis and was conducted with controversial data to accurately assess the issue. We collected relevant TCGA data to further testify the result. In addition, bioinformatics analysis was conducted to investigate the mechanism and related pathways of LncRNA UCA1 in esophageal carcinoma. METHODS: Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science were thoroughly searched for relevant information. Two reviewers independently performed data extraction and literature quality evaluation. Odd ratio and its 95% confidence intervals were applied to evaluate the relationship between LncRNA UCA1 and clinicopathological characteristics of esophageal carcinoma patients. Hazard ratios and its 95% confidence intervals were adopted to assess the prognostic effects of LncRNA UCA1 on overall survival and disease-free survival. Meta-analysis was performed with Stata 14.0 software. To further assess the function of LncRNA UCA1 in esophageal carcinoma, relevant data from The Cancer Genome Atlas (TCGA) database was collected. Three databases, miRWalk, TargetScan, and miRDB, were used for prediction of target genes. Genes present in these 3 databases were considered as predicted target genes of LncRNA UCA1. Venny 2.1 were used for intersection analysis. Subsequently, GO, KEGG, and PPI network analysis were conducted based on the overlapping target genes of LncRNA UCA1 to explore the possible molecular mechanism in esophageal carcinoma. RESULTS: This study provides a high-quality medical evidence for the correlation between LncRNA UCA1 expression and overall survival, and between disease-free survival and clinicopathological features. Based on bioinformatics analysis, this study enhanced the understanding of the mechanism and related pathways of LncRNA UCA1 in esophageal carcinoma. CONCLUSION: The study provides updated evidence to evaluate whether the expression of LncRNA UCA1 is in association with poor prognosis in patients with esophageal carcinoma. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/8MCHW.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma/mortalidad , Neoplasias Esofágicas/mortalidad , ARN Largo no Codificante/metabolismo , Biomarcadores de Tumor/análisis , Carcinoma/genética , Carcinoma/patología , Biología Computacional , Supervivencia sin Enfermedad , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Esófago/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Metaanálisis como Asunto , Pronóstico , Mapeo de Interacción de Proteínas , Mapas de Interacción de Proteínas/genética , ARN Largo no Codificante/análisis , Revisiones Sistemáticas como Asunto
18.
Medicine (Baltimore) ; 100(16): e25507, 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33879685

RESUMEN

BACKGROUND: Long noncoding RNA (lncRNA) is reported to be upregulated in many tumors. Although the expression of lncRNA in oral squamous cell carcinoma has been assessed, the association between lncRNA expression and prognosis or clinicopathological feature still remains controversial. Therefore, we conducted a meta-analysis to verify whether lncRNA expression was related to prognosis or clinicopathological features in patients with oral squamous cell carcinoma. METHODS: We searched Embase, PubMed, Web of Science, Cochrane library, Chinese National Knowledge Infrastructure, and Wanfang databases from inception to February 2021. The language included Chinese and English. The published literature on lncRNA expression and prognosis or clinicopathological characteristics of patients with oral squamous cell carcinoma was statistically analyzed. The combination of hazard ratios (HRs), odds ratios (OR), and 95% confidence intervals (95% CIs) were applied to evaluate the effects of lncRNA on the prognosis and clinicopathological features of oral squamous cell carcinoma. RESULTS: This study could provide a comprehensive review of the available evidence of lncRNA on the prognosis and clinicopathological features of oral squamous cell carcinoma. CONCLUSION: The conclusion of our study will provide the updated evidence to judge the lncRNA on the prognosis and clinicopathological features of oral squamous cell carcinoma.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Boca/mortalidad , ARN Largo no Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Biomarcadores de Tumor/análisis , Regulación Neoplásica de la Expresión Génica , Humanos , Metaanálisis como Asunto , Mucosa Bucal/patología , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/genética , Neoplasias de la Boca/terapia , Estadificación de Neoplasias , Pronóstico , ARN Largo no Codificante/análisis , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Revisiones Sistemáticas como Asunto
19.
Medicine (Baltimore) ; 100(17): e25555, 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33907102

RESUMEN

BACKGROUND: The immune checkpoint programmed cell death-1 (PD-1) plays a critical role in immune regulation. Recent studies have demonstrated functional PD-1 expression in peripheral sensory neurons, which contributes to neuronal excitability, pain, and opioid analgesia. However, the relationship between the expression of soluble programmed cell death-1(sPD-1) and cancer pain is controversial. The purpose of this study was to evaluate the relationship between sPD-1 expression level and cancer pain through meta-analysis. METHODS: Studies were selected from Pubmed, Web of science, Embase, Google Scholar, and Chinese National Knowledge Infrastructure, and the Chinese Biomedical Literature Database based on inclusion and exclusion criteria. The standard mean difference (SMD) and 95% confidence interval (CI) were calculated using the random-effect model or fixed-effect model to assess the association between sPD-1 expression level and cancer pain. All analyses were performed with the Stata 14 software. RESULTS: This review will be disseminated in print by peer-review. CONCLUSION: The results of this study will help us to determine whether the expression level of sPD-1 is related to cancer pain. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not endanger participant rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/WDPUY.


Asunto(s)
Dolor en Cáncer/etiología , Neoplasias/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Biomarcadores de Tumor/metabolismo , Estudios de Casos y Controles , Humanos , Metaanálisis como Asunto , Neoplasias/complicaciones , Proyectos de Investigación , Revisiones Sistemáticas como Asunto
20.
Arq Gastroenterol ; 58(1): 55-60, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33909798

RESUMEN

BACKGROUND: Colorectal cancer is the third most common neoplasm in the world. Methylation of tumor related genes in CpG islands can cause gene silencing and been involved in the development of cancer. The potential role of DKK2 as a biomarker for early diagnosis of colorectal cancer remains unclear. OBJECTIVE: The aim of the study was to evaluate the profile of methylation and RNAm expression of DKK2 as potential predictors of colorectal cancer diagnosis and prognosis. METHODS: Expression of mRNAs encoding DKK2 in 35 colorectal cancer tissues was quantified using real-time polymerase chain reaction analysis. The DNA methylation was studied by high resolution melting analysis. The general characteristics of the patients were collected. DKK2 methylation and expression were compared to clinical, pathological aspects and overall survival. RESULTS: Among the 35 patients studied, 18 were male, 10 were on right colon and 25 on left colon. Among the 20 patients with high hypermethylation, 15 of them had mRNA low expression of DKK2. There was no significant association between DKK2 promoter methylation and mRNA DKK2 expression and clinical or pathological features. DKK2 promoter methylation (P=0.154) and DKK2 RNA expression (P=0.345) did not show significant correlation with overall survival. CONCLUSION: DKK2 promoter methylation and DKK2 RNA status appear to be biomarkers of cancer diagnosis but not predictors of prognosis.


Asunto(s)
Neoplasias Colorrectales , Metilación de ADN , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/genética , Islas de CpG , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Masculino , Pronóstico , Regiones Promotoras Genéticas
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