RESUMEN

Infantile hemangioma (IH) is the most common benign vascular tumor during infancy and childhood and is characterized by abnormal vascular development. It is the most common vascular tumor and its related mechanisms and treatments remain a problem. IH-related biomarkers have been identified using transcriptome analysis and can be used to predict clinical outcomes. This study aimed to identify the key target genes for IH treatment and explore their possible roles in the IH pathophysiology. Gene records were acquired from the Gene Expression Omnibus database. Utilizing integrated weighted gene co-expression network examination, gene clusters were determined. Single-sample gene set enrichment analysis was performed to gauge immune infiltration. Essential genes were identified via Random Forest and Least Absolute Selection and Shrinkage Operator analyses. Ultimately, a set of five pivotal genes associated with the ailment was identified (NETO2, IDO1, KDR, MEG3, and TMSB15A). A nomogram for predicting IH diagnosis was constructed based on hub genes. The calibration curve showed valid agreement between the prediction and conclusion that the key genes in the model were clinically significant. Neuropilin and Tolloid-like 2 (NETO2) are closely associated with tumor development. The role value of NETO2 expression levels increased in hemangioma-derived endothelial cells (HemECs). After silencing NETO2, the growth and migration of cancer cells were significantly restrained. This study revealed the critical role of NETO2 in IH development, suggesting that targeting NETO2 may be effective in improving the therapeutic outcome of IH.

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INTRODUCTION: Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related deaths globally, with a five-year survival rate of only 5%. OBJECTIVES: Pancreatic ductal adenocarcinoma is often fatal because of the lack of specific early symptoms and effective early screening tools. Therefore, 80%-85% of patients are usually diagnosed in the advanced stages. This study aimed to investigate the analgesic effect of transcutaneous electrical acupoint stimulation in patients with advanced pancreatic cancer. METHODS: Eighty patients with advanced pancreatic cancer were recruited from the Integrative Medicine Department of our hospital between June 2017 and October 2018 and randomly divided into the experimental group ( n = 40) and the control group ( n = 40). The experimental group received transcutaneous electrical acupoint stimulation combined with analgesic medication for 3 consecutive days, while the control group received only analgesic medication. The pain scores of the two groups before and after intervention were compared. RESULTS: The mean pain severity score was significantly lower in the experimental group than in the control group on day 1 ( P < 0.001), day 2 ( P < 0.001), day 3 ( P = 0.005), and day 4 ( P = 0.043). CONCLUSION: Transcutaneous electrical acupoint stimulation therapy effectively alleviates the pain of patients with advanced pancreatic cancer with a high degree of safety and minimal adverse effects, and is worthy of clinical application.

Asunto(s)

Puntos de Acupuntura , Dolor en Cáncer , Manejo del Dolor , Neoplasias Pancreáticas , Estimulación Eléctrica Transcutánea del Nervio , Humanos , Femenino , Masculino , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/terapia , Persona de Mediana Edad , Estimulación Eléctrica Transcutánea del Nervio/métodos , Manejo del Dolor/métodos , Anciano , Dolor en Cáncer/terapia , Dolor en Cáncer/etiología , Dolor en Cáncer/diagnóstico , Dimensión del Dolor , Resultado del Tratamiento , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/complicaciones , Terapia Combinada

RESUMEN

Internal mildewed nutmeg is difficult to perceive without cutting the nutmeg open and examining it carefully, which poses a significant risk to public health. At present, macroscopic identification and chromatographic analysis are applied to determine whether nutmeg is moldy or not. However, the former relies on a human panel, with the disadvantages of subjectivity and empirical dependence, whilst the latter is generally time-consuming and requires organic solvents. Therefore, it is urgent to develop a rapid and feasible approach for evaluating the quality and predicting mildew in nutmeg. In this study, the quality and odor characteristics of five groups of nutmeg samples with different degrees of mildew were analyzed by using the responses of an electronic nose combined with chemical profiling. The main physicochemical indicators, such as the levels of α-pinene, ß-pinene, elemicin, and dehydro-di-isoeugenol, were determined. The results revealed that the contents of α-pinene, ß-pinene, and elemicin changed significantly with the extension of storage time. Through the use of an electronic nose and HS-GC-MS technology to assess the overall odor characteristics of nutmeg samples, it was found that the production of volatile organic compounds (VOCs) such as ammonia/organic amines, carbon monoxide, ethanol, and hydrogen sulfide, as well as changes in the terpene and phenylpropene components of the nutmeg itself, may be the material basis for the changes in odor. The accuracy of the qualitative classification model for the degree of mildew in nutmeg was higher than 90% according to the electronic nose data combined with different machine learning algorithms. Quantitative models were established for predicting the contents of the chemical components, and models based on a BP neural network (BPNN), the support vector machine (SVM), and the random forest algorithm (RF) all showed good performance in predicting the concentrations of these chemical components, except for dehydro-di-isoeugenol. The BPNN performed effectively in predicting the storage time of nutmeg on the basis of the E-nose's responses, with an RMSE and R2 of 0.268 and 0.996 for the training set, and 0.317 and 0.993 for the testing set, respectively. The results demonstrated that the responses of the electronic nose (E-nose) had a high correlation with the internal quality of nutmeg. This work proposes a quick and non-destructive evaluation method for the quality of nutmeg, which has high accuracy in discriminating between different degrees of mold in nutmeg and is conducive to early detection and warning of moldy phenomena.

Asunto(s)

Myristica , Humanos , Nariz Electrónica , Hongos

RESUMEN

The odor fingerprint of Pollygonati Rhizoma samples with different mildewing degrees was analyzed and the relationship between the odor variation and the mildewing degree was explored. A fast discriminant model was established according to the response intensity of electronic nose. The α-FOX3000 electronic nose was applied to analyze the odor fingerprint of Pollygonati Rhizoma samples with different mildewing degrees and the radar map was used to analyze the main contributors among the volatile organic compounds. The feature data were processed and analyzed by partial least squares discriminant analysis(PLS-DA), K-nearest neighbor(KNN), sequential minimal optimization(SMO), random forest(RF) and naive Bayes(NB), respectively. According to the radar map of the electronic nose, the response values of three sensors, namely T70/2, T30/1, and P10/2, increased with the mildewing, indicating that the Pollygonati Rhizoma produced alkanes and aromatic compounds after the mildewing. According to PLS-DA model, Pollygonati Rhizoma samples of three mildewing degrees could be well distinguished in three areas. Afterwards, the variable importance analysis of the sensors was carried out and then five sensors that contributed a lot to the classification were screened out: T70/2, T30/1, PA/2, P10/1 and P40/1. The classification accuracy of all the four models(KNN, SMO, RF, and NB) was above 90%, and KNN was most accurate(accuracy: 97.2%). Different volatile organic compounds were produced after the mildewing of Pollygonati Rhizoma, and they could be detected by electronic nose, which laid a foundation for the establishment of a rapid discrimination model for mildewed Pollygonati Rhizoma. This paper shed lights on further research on change pattern and quick detection of volatile organic compounds in moldy Chinese herbal medicines.

Asunto(s)

Medicamentos Herbarios Chinos , Compuestos Orgánicos Volátiles , Nariz Electrónica , Odorantes/análisis , Compuestos Orgánicos Volátiles/análisis , Teorema de Bayes , Medicamentos Herbarios Chinos/análisis , Análisis Discriminante

RESUMEN

Nutmeg (Myristicae Semen), the so-called Rou-Dou-Kou in Chinese, is one kind of Chinese herbal medicines (CHMs) as well as a globally popular spice. Hence, its stable quality and safe application attract more attention. However, it is highly prone to mildew during storage due to its rich volatile components and fatty oil. Therefore, in this study, an electronic nose (E-nose) was introduced to attempt to reliably and rapidly identify nutmeg samples with different degrees of mildew. Meanwhile, the chemical composition and volatile oil were analyzed using HPLC fingerprint and GC-MS, respectively, which could support and validate the result of E-nose. The results showed that the cluster results of HPLC fingerprint and GC-MS were generally consistent with E-nose, and they all clustered into two categories. Additionally, a discriminant model was established, which divided the samples into three categories: mildew-free, mildew-slight, and mildew, and a high DPR was obtained, which indicates that the E-nose could be a novel and promising approach for the establishment of a quality evaluation system to identify CHMs with different degrees of mildew rapidly, especially to identify early mildew.

RESUMEN

Identification of clinically applicable molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) is crucial to improving patient outcomes. However, the traditional tissue-dependent transcriptional subtyping strategies are invasive and not amenable to routine clinical evaluation. In this study, we developed a circulating extracellular vesicle (cEV) long RNA (exLR)-based PDAC subtyping method and provided exLR-derived signatures for predicting immunogenic features and clinical outcomes in PDAC. We enrolled 426 individuals, among which 227 PDACs served as an internal cohort, 118 PDACs from two other medical centers served as an independent validation cohort, and 81 healthy individuals served as the control. ExLR sequencing was performed on all plasma samples. We found that PDAC could be categorized into three subtypes based on plasma exLR profiles. Each subpopulation showed its own molecular features and was associated with patient clinical prognosis. The immunocyte-derived cEV fractions were altered among PDAC subtypes and interconnected with tumor-infiltrating lymphocytes in cancerous tissue. Additionally, we found a significant concordance of immunoregulators between tissue and blood EVs, and we harvested potential PDAC therapeutic targets. Most importantly, we constructed a nine exLR-derived, tissue-applicable signature for prognostic assessment of PDAC. The circulating exLR-based features may offer an attractive platform for personalized treatment and predicting patient outcomes in multiple types of cancer.

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While collaborative writing has been increasingly investigated in educational research, little is known about whether and how it is adopted as a pedagogical activity in classroom contexts. This exploratory study investigated EFL teachers' perceptions of the implementation of collaborative writing in Chinese tertiary institutions. The analysis of in-depth interviews with 31 EFL teachers from 13 institutions in the People's Republic of China and their teaching materials reveals mismatches between their perceptions and practices, as well as their perceptions and knowledge. While the teachers perceived collaborative writing as valuable and feasible, more than half of them were not using it, and their perceptions were not supported by sound teacher knowledge. Practical implications are provided for implementing collaborative writing in classroom contexts.

RESUMEN

BACKGROUND: Kaempferol, a natural flavonoid, exhibits anticancer properties by scavenging reactive oxygen species (ROS). However, increasing evidence has demonstrated that, under certain conditions, kaempferol can inhibit tumor growth by upregulating ROS levels. In this study, we aimed to investigate whether kaempferol effectively suppresses pancreatic cancer through upregulation of ROS, and to explore the underlying molecular mechanism. METHODS: PANC-1 and Mia PaCa-2 cells were exposed to different concentrations of kaempferol. Cell proliferation and colony formation were evaluated by CCK-8 and colony formation assays. Flow cytometry was performed to assess the ROS levels and cell apoptosis. The mRNA sequencing and KEGG enrichment analysis were performed to identify differentially expressed genes and to reveal significantly enriched signaling pathways in response to kaempferol treatment. Based on biological analysis, we hypothesized that tissue transglutaminase (TGM2) gene was an essential target for kaempferol to induce ROS-related apoptosis in pancreatic cancer. TGM2 was overexpressed by lentivirus vector to verify the effect of TGM2 on the ROS-associated apoptotic signaling pathway. Western blot and qRT-PCR were used to determine the protein and mRNA levels, respectively. The prognostic value of TGM2 was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) tools based on public data from the TCGA database. RESULTS: Kaempferol effectively suppressed pancreatic cancer in vitro and in vivo. Kaempferol promoted apoptosis in vitro by increasing ROS generation, which was involved in Akt/mTOR signaling. TGM2 levels were significantly increased in PDAC tissues compared with normal tissues, and high TGM2 expression was positively correlated with poor prognosis in pancreatic cancer patients. Decreased TGM2 mRNA and protein levels were observed in the cells after treatment with kaempferol. Additionally, TGM2 overexpression downregulated ROS production and inhibited the abovementioned apoptotic signaling pathway. CONCLUSIONS: Kaempferol induces ROS-dependent apoptosis in pancreatic cancer cells via TGM2-mediated Akt/mTOR signaling, and TGM2 may represent a promising prognostic biomarker for pancreatic cancer.

Asunto(s)

Apoptosis/efectos de los fármacos , Proteínas de Unión al GTP/metabolismo , Quempferoles/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Transglutaminasas/metabolismo , Animales , Antineoplásicos Fitogénicos , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular , Modelos Animales de Enfermedad , Proteínas de Unión al GTP/genética , Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Modelos Biológicos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proteína Glutamina Gamma Glutamiltransferasa 2 , Transglutaminasas/genética , Neoplasias Pancreáticas

RESUMEN

AIMS: Our aim was to assess the risk of cardiovascular disease (CVD) mortality in US 5-year survivors of adolescent and young adult (AYA) cancer compared with those of the general population and contemporaneous 5-year survivors of childhood cancer. METHODS AND RESULTS: A total of 160 834 5-year AYA cancer survivors (aged 15-39 years at diagnosis) were included, representing 2 239 390 person-years of follow-up. Overall, 2910 CVD deaths occurred, which was 1.4-fold [95% confidence interval (CI) 1.3-1.4] that expected in the general population, corresponding to 3.6 (95% CI 3.2-3.9) excess CVD deaths per 10 000 person-years. The highest risk of cardiac mortality was experienced after Hodgkin's lymphoma (HL), and the highest risk of cerebrovascular mortality was observed with central nervous system (CNS) tumours. Even survivors in their 6th and 7th decades of life, the risk of CVD mortality remained markedly higher than that of the matched general population. Competing risk analysis showed that the cumulative mortality of CVD was elevated among AYA cancer survivors compared with childhood cancer survivors during the whole study period. CONCLUSION: Long-term AYA cancer survivors have a greater risk of CVD mortality than the US general population and childhood cancer survivors. Vulnerable subgroups, especially survivors of HL and CNS tumours, require continued close follow-up care for cardiovascular conditions throughout survivorship.

Asunto(s)

Supervivientes de Cáncer , Enfermedades Cardiovasculares , Neoplasias , Adolescente , Adulto , Cuidados Posteriores , Estudios de Cohortes , Humanos , Factores de Riesgo , Sobrevivientes , Estados Unidos/epidemiología , Adulto Joven

RESUMEN

INTRODUCTION: Typical testicular epidermoid cysts (TECs) manifestate as a target sign or onion skin sign on ultrasonography and magnetic resonance (MR) imaging. Clinicians are increasingly aware of the imaging characteristics of typical TECs, which allow accurate diagnosis and successful treatment while preserving the testicle, but atypical TECs are likely to be misdiagnosed as a malignant intratesticular neoplasm, leading to complete testicular resection. PATIENT CONCERNS: A 26 year-old male patient complained of a painless enlargement of the left testicle that had been present for 1 month. The patient had no recent medical history of scrotal trauma or systemic infection. DIAGNOSIS: A round 48 mm × 45 mm × 43 mm mass was seen inside the left testicle. T2-weighted images of the lesion showed a thin hypointense capsule. T1-weighted images of the lesion showed a hyperintense nodule on the cyst wall, which appeared hypointense on T2-weighted and SPAIR images. After Gd-DTPA injection, the lesion was not enhanced; however, the nodule was enhanced on THRIVE images. These manifestations were consistent with a benign intratesticular lesion, and MR imaging diagnosed atypical TEC, which was confirmed by pathology after surgery. INTERVENTIONS: The patient was treated with organ-sparing surgery with testicular enucleation. OUTCOMES: The patient was re-examined with ultrasonography 3 months after surgery. The left residual testicular tissue appeared normal, and reproductive function was preserved. CONCLUSION: Urologists must be aware of the clinical and MR imaging characteristics of atypical TECs and the utility of preoperative MR imaging for the diagnosis of testicular lesions to ensure that organ-sparing surgery is performed rather than unnecessary orchiectomy.

Asunto(s)

Quiste Epidérmico/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Enfermedades Testiculares/diagnóstico por imagen , Adulto , Diagnóstico Diferencial , Quiste Epidérmico/cirugía , Humanos , Masculino , Enfermedades Testiculares/cirugía

RESUMEN

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose at resectable stage. Recent studies have suggested that extracellular vesicles (EVs) contain long RNAs. The aim of this study was to develop a diagnostic (d-)signature for the detection of PDAC based on EV long RNA (exLR) profiling. DESIGN: We conducted a case-control study with 501 participants, including 284 patients with PDAC, 100 patients with chronic pancreatitis (CP) and 117 healthy subjects. The exLR profile of plasma samples was analysed by exLR sequencing. The d-signature was identified using a support vector machine algorithm and a training cohort (n=188) and was validated using an internal validation cohort (n=135) and an external validation cohort (n=178). RESULTS: We developed a d-signature that comprised eight exLRs, including FGA, KRT19, HIST1H2BK, ITIH2, MARCH2, CLDN1, MAL2 and TIMP1, for PDAC detection. The d-signature showed high accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.960, 0.950 and 0.936 in the training, internal validation and external validation cohort, respectively. The d-signature was able to identify resectable stage I/II cancer with an AUC of 0.949 in the combined three cohorts. In addition, the d-signature showed superior performance to carbohydrate antigen 19-9 in distinguishing PDAC from CP (AUC 0.931 vs 0.873, p=0.028). CONCLUSION: This study is the first to characterise the plasma exLR profile in PDAC and to report an exLR signature for the detection of pancreatic cancer. This signature may improve the prognosis of patients who would have otherwise missed the curative treatment window.

Asunto(s)

Carcinoma Ductal Pancreático/sangre , Carcinoma Ductal Pancreático/diagnóstico , Vesículas Extracelulares/metabolismo , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/diagnóstico , ARN/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , alfa-Globulinas/genética , Área Bajo la Curva , Antígeno CA-19-9/sangre , Carcinoma Ductal Pancreático/genética , Estudios de Casos y Controles , Niño , Claudina-1/genética , Femenino , Fibrinógeno/genética , Humanos , Queratina-19/genética , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Proteínas Proteolipídicas Asociadas a Mielina y Linfocito/genética , Neoplasias Pancreáticas/genética , Pancreatitis Crónica/sangre , ARN Circular/sangre , ARN Largo no Codificante/sangre , ARN Mensajero/sangre , Curva ROC , Análisis de Secuencia de ARN , Máquina de Vectores de Soporte , Inhibidor Tisular de Metaloproteinasa-1/genética , Ubiquitina-Proteína Ligasas/genética , Adulto Joven

RESUMEN

Using latent profile analyses and based on two-wave data from 5,388 Chinese adolescents (Mage  = 15.79, SD = 0.66; 51.99% females), this study examined the variety of ways in which adolescents' perceived career-related parental processes (i.e., parental expectations, support, interference, barriers to engagement, and parent-child congruence) may be configured within families and how such configurations may be associated with adolescents' career adaptability and ambivalence one year later. Three meaningful profiles were identified: the "Supportive but not Intrusive" (SNI) profile, the "Unsupportive but not Permissive" (UNP) profile, and the "Ambivalent and Controlling" (AC) profile. Adolescents in the UNP profile reported higher levels of career ambivalence and lower levels of career adaptability than did those in either the SNI or the AC profiles. Implications for career development among Chinese adolescents were discussed.

Asunto(s)

Selección de Profesión , Responsabilidad Parental/psicología , Adolescente , China , Femenino , Humanos , Masculino , Relaciones Padres-Hijo , Encuestas y Cuestionarios

RESUMEN

A novel palladium-catalyzed protocol for the synthesis of 2-arylquinolines via tandem reaction of 2-aminostyryl nitriles with arylboronic acids has been developed with good functional group tolerance. The presented approach offers a new synthetic pathway toward the core structures of 2-arylquinolines compared to classical condensation reaction of (E)-2-aminostyryl aryl ketones. Moreover, the present synthetic route could be readily scaled up to gram quantity without difficulty. Preliminary mechanistic experiments showed that this transformation involves a nucleophilic addition of aryl palladium species to the nitrile to generate an aryl ketone intermediate followed by an intramolecular cyclization and dehydration to quinoline ring.

RESUMEN

In the initial published version of this article, there was a mistake in the P value for the correlation between gene-expression changes and 5 hmC changes in tumors. The correct P value should be same as the P value shown in Fig. S6A: 9.8 × 10-6 (mistakenly shown as "9.8 × 106" in the main text). This correction does not affect the description of results or the conclusions of this study, since the range of P value is between 0 and 1.

RESUMEN

BACKGROUND: Extracellular vesicles (EVs) contain a rich cargo of different RNA species with specialized functions and clinical applications. However, the landscape and characteristics of extracellular vesicle long RNA (exLR) in human blood remain largely unknown. METHODS: We presented an optimized strategy for exLR sequencing (exLR-seq) of human plasma. The sample cohort included 159 healthy individuals, 150 patients with cancer (5 cancer types), and 43 patients with other diseases. Bioinformatics approaches were used to analyze the distribution and features of exLRs. Support vector machine algorithm was performed to construct the diagnosis classifier, and diagnostic efficiency was evaluated by ROC analysis. RESULTS: More than 10000 exLRs, including mRNA, circRNA, and lncRNA, were reliably detected in each exLR-seq sample from 1-2 mL of plasma. We observed that blood EVs contain a substantial fraction of intact mRNAs and a large number of assembling spliced junctions; circRNA was also enriched in blood EVs. Interestingly, blood exLRs reflected their tissue origins and the relative fractions of different immune cell types. Additionally, the exLR profile could distinguish patients with cancer from healthy individuals. We further showed that 8 exLRs can serve as biomarkers for hepatocellular carcinoma (HCC) diagnosis with high diagnostic efficiency in training [area under the curve (AUC) = 0.9527; 95% CI, 0.9170-0.9883], validation cohort (AUC = 0.9825; 95% CI, 0.9606-1), and testing cohort (AUC = 0.9627; 95% CI, 0.9263-0.9991). CONCLUSIONS: In summary, this study revealed abundant exLRs in human plasma and identified diverse specific markers potentially useful for cancer diagnosis.

Asunto(s)

Biomarcadores de Tumor/sangre , Vesículas Extracelulares/metabolismo , Neoplasias/diagnóstico , ARN Circular/sangre , ARN Largo no Codificante/sangre , ARN Mensajero/sangre , Femenino , Humanos , Masculino , Neoplasias/sangre , ARN Circular/genética , ARN Largo no Codificante/genética , ARN Mensajero/genética , Análisis de Secuencia de ARN

RESUMEN

This study examined the unique and interactive effects of various career-specific parenting practices (i.e., parental career support, interference, and lack of engagement) on Chinese high school students' career decision-making self-efficacy (CDSE) as well as the mediating role of autonomy in such associations. Based on data from 641 Chinese high school students (47.6% male; mean age = 15.28 years old, SD = 0.49) in 2016, two moderated mediating effects were identified. Higher level of parental career engagement strengthened the positive association between parental career support and adolescents' autonomy, which in turn, was associated positively with adolescents' CDSE. Parental career interference related negatively with adolescents' CDSE via autonomy when lack of parental career engagement was low, but related positively with adolescents' CDSE via autonomy when lack of parental career engagement was high. These findings advance our understanding of the underlying processes between career-specific parenting practices and adolescents' CDSE. Implications for practices were discussed.

RESUMEN

OBJECTIVES: Recent studies have suggested that the CXCL9, 10, 11/CXCR3 axis is significant in immune regulation and therapeutic efficacy in human cancers; however, its role in pancreatic ductal adenocarcinoma (PDAC) remains unknown. This study serves to evaluate the prognostic prediction value of plasma IFN-γ-inducible chemokines, CXCL9 and CXCL10, in advanced PDAC. METHODS: Two hundred patients with advanced PDAC receiving palliative chemotherapy were retrospectively recruited. The association between Plasma CXCL9/CXCL10 levels and survival time was first analyzed in a test group of 110 patients and then confirmed in a validation group of 90 patients. RESULTS: High levels of CXCL9 and CXCL10 were significantly correlated with longer overall survival (OS) in advanced PDAC patients (314 vs. 136 days for CXCL9, P < 0.0001, and 374 vs. 163 days for CXCL10, P < 0.0001, respectively) in the test group, which was consistent with the results derived from the validation group. In addition, high levels of CXCL9 and CXCL10 were associated with longer time to progression (TTP) in patients receiving chemotherapy (100 vs. 60 days for CXCL9, P = 0.0021, and 104 vs. 67 days for CXCL10, P = 0.0057, respectively). Multivariate analyses confirmed that CXCL9 and CXCL10 were independent prognostic predictors for OS (hazard ratio [HR]: 0.452, P < 0.001 for CXCL9; and HR: 0.586, P = 0.007 for CXCL10, respectively) and TTP (HR: 0.656, P = 0.015 for CXCL9; and HR: 0.687, P = 0.040 for CXCL10, respectively). CONCLUSIONS: Plasma CXCL9 and CXCL10 can be used to predict survival of advanced PDAC patients receiving chemotherapy, allowing clinicians to potentially improve treatment outcomes by identifying candidates for aggressive therapy.

Asunto(s)

Antineoplásicos/uso terapéutico , Carcinoma Ductal Pancreático/sangre , Quimiocina CXCL10/metabolismo , Quimiocina CXCL9/metabolismo , Interferón gamma/farmacología , Quimiocina CXCL10/sangre , Quimiocina CXCL10/genética , Quimiocina CXCL9/sangre , Quimiocina CXCL9/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas , Estudios Retrospectivos , Neoplasias Pancreáticas

RESUMEN

Pancreatic cancer is one of the most aggressive human malignancies and is associated with a dismal prognosis, which can be contributed to its atypical symptoms, metastatic propensity, and significant chemoresistance. Emerging evidence shows that pancreatic cancer cell-derived exosomes (PEXs) play critical roles in tumorigenesis and tumor development, as they are involved in drug resistance, immune evasion and metabolic reprograming, and distant metastasis of pancreatic cancer. Their numerous differentially expressed and functional contents make PEXs promising screening tools and therapeutic targets, which require further exploration. In this review, we focus on the functions of PEX contents and their clinical implications in pancreatic cancer.

Asunto(s)

Exosomas/patología , Neoplasias Pancreáticas/patología , Animales , Exosomas/metabolismo , Humanos , Neoplasias Pancreáticas/metabolismo

RESUMEN

Exosomes, which are nanosized endocytic vesicles that are secreted by most cells, contain an abundant cargo of different RNA species that can modulate the behavior of recipient cells and may be used as circulating biomarkers for diseases. Here, we develop a web-accessible database (http://www.exoRBase.org), exoRBase, which is a repository of circular RNA (circRNA), long non-coding RNA (lncRNA) and messenger RNA (mRNA) derived from RNA-seq data analyses of human blood exosomes. Experimental validations from the published literature are also included. exoRBase features the integration and visualization of RNA expression profiles based on normalized RNA-seq data spanning both normal individuals and patients with different diseases. exoRBase aims to collect and characterize all long RNA species in human blood exosomes. The first release of exoRBase contains 58 330 circRNAs, 15 501 lncRNAs and 18 333 mRNAs. The annotation, expression level and possible original tissues are provided. exoRBase will aid researchers in identifying molecular signatures in blood exosomes and will trigger new exosomal biomarker discovery and functional implication for human diseases.

Asunto(s)

Bases de Datos de Ácidos Nucleicos , Exosomas/genética , ARN/sangre , ARN/genética , Humanos , Internet , ARN Circular , ARN Largo no Codificante/sangre , ARN Largo no Codificante/genética , ARN Mensajero/sangre , ARN Mensajero/genética , Análisis de Secuencia de ARN

RESUMEN

Circular RNA (circRNA), a recently discovered subclass of non-coding RNAs (ncRNAs), forms a covalently closed loop with neither a 5' cap structure nor a 3' polyadenylated tail. Generated from precursor mRNA (pre-mRNA) through "backsplicing" (a type of alternative RNA splicing), the majority of circRNAs are located in the cytoplasm and are widespread among living organisms. They are stable and conserved and exhibit spatiotemporal-specific expression. CircRNAs are known to be involved in the development and progression of multiple diseases, including cancer, by acting as microRNA (miRNA) sponges and by regulating processes such as transcription and translation. The extensively aberrant expression profiles of circRNAs in multiple cancerous tissues make these molecules promising diagnostic biomarkers and therapeutic targets for cancer. Here, we briefly review the characteristics, biogenesis, classification, and functions of circRNAs, with a particular focus on the role of circRNAs in various cancers.

Asunto(s)

Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica/genética , Neoplasias/genética , Neoplasias/patología , ARN , Animales , Humanos , ARN Circular