scholarly journals Serum miR-483-5p and miR-195 are predictive of recurrence risk in adrenocortical cancer patients

2013 ◽  
Vol 20 (4) ◽  
pp. 579-594 ◽  
Author(s):  
O Chabre ◽  
R Libé ◽  
G Assie ◽  
O Barreau ◽  
J Bertherat ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Serum Levels ◽  
Recurrence Risk ◽  
Adrenocortical Cancer ◽  
Serum Samples ◽  
Adrenocortical Adenomas ◽  
Mirna Expression Profiles ◽  
Noninvasive Biomarkers ◽  
First Time ◽  
Circulating Levels

Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Local and distant recurrences occur in a subset of tumors classified as ‘aggressive’ ACC (aACC), as opposed to ‘non-aggressive’ ACC (naACC). In this study, we investigated whether tissue and serum microRNAs (miRNAs) are predictive of ACC prognosis. Tissue miRNA expression profiles were determined using microarrays in a test series of six adrenocortical adenomas (ACAs), six naACCs, and six aACCs. Eight miRNAs were selected for further validation by quantitative RT-PCR (ten ACAs, nine naACCs, nine aACCs, and three normal adrenals). Serum levels of five miRNAs were measured in samples from 56 subjects (19 healthy controls (HC), 14 ACA, nine naACC, and 14 aACC patients). MiR-195 and miR-335 levels were significantly decreased in both tumor and serum samples of ACC patients relative to ACA patients or HC. MiR-139-5p and miR-376a levels were significantly increased in aACC compared with naACC patients in tumor samples only. Tissue miR-483-5p was markedly upregulated in a majority of ACC compared with ACA patients or HC, but most importantly, serum miR-483-5p was detected only in aACC patients. High circulating levels of miR-483-5p or low circulating levels of miR-195 were associated with both shorter recurrence-free survival (P=0.0004 and P=0.0014 respectively) and shorter overall survival (P=0.0005 and P=0.0086 respectively). In conclusion, this study reports for the first time that circulating miR-483-5p and miR-195 are promising noninvasive biomarkers with a highly specific prognostic value for the clinical outcome of ACC patients.

Elevated circulating levels of tumor necrosis factor predict unresponsiveness to treatment with interferon alfa-2b in chronic myelogenous leukemia.

1992 ◽  
Vol 10 (4) ◽  
pp. 631-634 ◽  
Author(s):  
F Herrmann ◽  
S G Helfrich ◽  
A Lindemann ◽  
E Schleiermacher ◽  
C Huber ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Chronic Myelogenous Leukemia ◽  
Tumor Necrosis ◽  
Performance Status ◽  
Chronic Phase ◽  
Serum Levels ◽  
Myelogenous Leukemia ◽  
Serum Samples ◽  
Circulating Levels ◽  
Necrosis Factor

PURPOSE The study was undertaken to analyze circulating tumor necrosis factor (TNF) levels in patients with chronic-phase chronic myelogenous leukemia (CML) undergoing interferon (IFN) alfa-2b therapy, and to correlate pretreatment serum levels of TNF with response to IFN alfa-2b therapy. PATIENTS AND METHODS Fourteen patients with CML in chronic phase were treated with recombinant human IFN alfa-2b for 7 to 39 months. RESULTS In eight patients IFN alfa-2b treatment failed due to lack of hematologic response. A complete or partial hematologic remission was achieved in the remaining six patients, of whom two patients experienced a complete cytogenetic response. Retrospective analysis of serum samples obtained from all patients before the onset of IFN alfa-2b administration revealed that levels (mean +/- SEM) of circulating TNF were higher (P less than .001) in the group of patients who did not respond to IFN alfa-2b treatment (157 +/- 15 U/mL) than in the responders (10.3 +/- 4 U/mL) or healthy control subjects (9.1 +/- 3 U/mL). However, there was no correlation between TNF serum levels and other patient characteristics at study enrollment including age, sex, duration of disease, performance status, splenomegaly, WBC count, platelet count, hemoglobin value, prior therapy, and prognostic category. CONCLUSION These findings indicate that circulating levels of TNF are increased in a subset of patients with chronic-phase CML and that this elevation is associated with poor response to IFN alfa-2b therapy.

scholarly journals Comprehensive Analysis of microRNA Profiles in Organoids Derived from Human Colorectal Adenoma and Cancer

Digestion ◽  
2021 ◽  
pp. 1-10
Author(s):  
Hiroshi Nagai ◽  
Masatake Kuroha ◽  
Tomoyuki Handa ◽  
Hideaki Karasawa ◽  
Shinobu Ohnuma ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Cell Communication ◽  
Colorectal Adenomas ◽  
Mirna Expression Profiles ◽  
Exosomal Mirna ◽  
The Impact ◽  
First Time ◽  
Ht 29

Introduction: Exosomes are membrane-enclosed nanovesicles, which are increasingly being recognized as important cell communication components for their role in transmitting microRNAs (miRNAs). No previous study has addressed the exosomal miRNA profile in colorectal adenomas (CRAs) because the long-term culture of CRA is challenging. This study aimed to identify the miRNA signature in organoid exosomes derived from human CRA and colorectal cancer (CRC) samples. Methods: Organoid cultures were developed from resected colorectal tissues of patients with CRA or CRC undergoing surgery or endoscopic mucosal resection. Exosomes were prepared from the conditioned medium of the organoids. miRNAs were prepared from the exosomes and their source organoids. The miRNA expression profiles were compared using microarray analysis. The impact of alteration of miRNA expression on cell proliferation was examined using miRNA mimics or inhibitors in HT-29 human CRC cells. Results: We established 6 organoid lines from CRC and 8 organoid lines from CRA. Exosomal miRNA signatures were different between the organoids derived from CRA and CRC. Both exosomal and cellular miR-1246 expressions were upregulated in CRC-derived organoids compared to their expression in CRA-derived organoids. Alteration of miR-1246 expression by the miR-1246 mimic or inhibitor increased or decreased cell proliferation in HT-29 cells, respectively. Conclusions: We report for the first time the miRNA profiles of exosomes in CRA- and CRC-derived organoids. The upregulation of miR-1246 might play a role in increased cell proliferation in the process of CRA-carcinoma transition.

scholarly journals American Ginseng Regulates Gene Expression to Protect against Premature Ovarian Failure in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Lei Zhu ◽  
Ji Li ◽  
Nannan Xing ◽  
Dongwei Han ◽  
Haixue Kuang ◽  
...  
Keyword(s):  
Premature Ovarian Failure ◽  
Expression Profiles ◽  
Serum Levels ◽  
American Ginseng ◽  
Ovarian Failure ◽  
Integrated Analysis ◽  
Vinylcyclohexene Diepoxide ◽  
Qrt Pcr ◽  
Ovarian Aging ◽  
Mirna Expression Profiles

Premature ovarian failure (POF) is defined as lost ovarian functions before the age of 40. Three possible molecular markers (PLA2G4A,miR-29a, andmiR-144) have been identified in our previous study by integrated analysis of mRNA and miRNA expression profiles. The present study aimed to evaluate American ginseng root’s protective potential against POF by studying transcriptional and protein variations between American ginseng treatments and controls in rats. 4-Vinylcyclohexene diepoxide (VCD) was administered to rats for 14 days to induce POF. Additionally, American ginseng was administered to POF rats for one month, andPLA2G4A,miR-29a, andmiR-144expressions were measured in rat ovaries by qRT-PCR. PLA2G4A protein expression was examined by Western Blot, and PGE2, LH, FSH, and E2 serum levels were detected by ELISA.PLA2G4AmRNA and protein were downregulated in American ginseng-treated rats,miR-29aandmiR-144levels increased, and PGE2serum levels decreased, while LH, FSH, and E2 increased compared to POF induction alone. Analysis of transcriptional and protein variations suggested that American ginseng protects the ovary against POF by regulating prostaglandin biosynthesis, ovulation, and preventing ovarian aging. High hormone levels (PGE2, FSH, and LH) were reduced, and E2 secretion approached normal levels, leading to improved POF symptoms and abnormal ovulation.

scholarly journals The miRNA Profile in Non-Hodgkin’s Lymphoma Patients with Secondary Myelodysplasia

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2318 ◽  
Author(s):  
Yuliya Andreevna Veryaskina ◽  
Sergei Evgenievich Titov ◽  
Igor Borisovich Kovynev ◽  
Tatiana Ivanovna Pospelova ◽  
Igor Fyodorovich Zhimulev
Keyword(s):  
Mirna Expression ◽  
Genetic Instability ◽  
Myeloid Leukemia ◽  
Precancerous Lesions ◽  
Expression Profiles ◽  
Epigenetic Factors ◽  
Blood Disorders ◽  
Hematopoietic Stem ◽  
Mirna Expression Profiles ◽  
First Time

Myelodysplastic syndromes are a group of clonal diseases of hematopoietic stem cells and are characterized by multilineage dysplasia, ineffective hematopoiesis, peripheral blood cytopenias, genetic instability and a risk of transformation to acute myeloid leukemia. Some patients with non-Hodgkin lymphomas (NHLs) may have developed secondary myelodysplasia before therapy. Bone marrow (BM) hematopoiesis is regulated by a spectrum of epigenetic factors, among which microRNAs (miRNAs) are special. The aim of this work is to profile miRNA expression in BM cells in untreated NHL patients with secondary myelodysplasia. A comparative analysis of miRNA expression levels between the NHL and non-cancer blood disorders samples revealed that let-7a-5p was upregulated, and miR-26a-5p, miR-199b-5p, miR-145-5p and miR-150-5p were downregulated in NHL with myelodysplasia (p < 0.05). We for the first time developed a profile of miRNA expression in BM samples in untreated NHL patients with secondary myelodysplasia. It can be assumed that the differential diagnosis for blood cancers and secondary BM conditions based on miRNA expression profiles will improve the accuracy and relevance of the early diagnosis of cancerous and precancerous lesions in BM.

scholarly journals A Comprehensive miRNome Analysis of Macrophages Isolated from db/db Mice and Selected miRNAs Involved in Metabolic Syndrome-Associated Cardiac Remodeling

2021 ◽  
Vol 22 (4) ◽  
pp. 2197
Author(s):  
Justyna Niderla-Bielińska ◽  
Aneta Ścieżyńska ◽  
Aneta Moskalik ◽  
Ewa Jankowska-Steifer ◽  
Krzysztof Bartkowiak ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Cardiac Remodeling ◽  
Cardiac Tissue ◽  
Expression Profiles ◽  
Mirna Expression Profiles ◽  
Macrophage Populations ◽  
Regulatory Functions ◽  
First Time ◽  
Two Populations ◽  
Generation Sequencing

Cardiac macrophages are known from various activities, therefore we presume that microRNAs (miRNAs) produced or released by macrophages in cardiac tissue have impact on myocardial remodeling in individuals with metabolic syndrome (MetS). We aim to assess the cardiac macrophage miRNA profile by selecting those miRNA molecules that potentially exhibit regulatory functions in MetS-related cardiac remodeling. Cardiac tissue macrophages from control and db/db mice (an animal model of MetS) were counted and sorted with flow cytometry, which yielded two populations: CD45+CD11b+CD64+Ly6Chi and CD45+CD11b+CD64+Ly6Clow. Total RNA was then isolated, and miRNA expression profiles were evaluated with Next Generation Sequencing. We successfully sequenced 1400 miRNAs in both macrophage populations: CD45+CD11b+CD64+Ly6Chi and CD45+CD11b+CD64+Ly6Clow. Among the 1400 miRNAs, about 150 showed different expression levels in control and db/db mice and between these two subpopulations. At least 15 miRNAs are possibly associated with MetS pathology in cardiac tissue due to direct or indirect regulation of the expression of miRNAs for proteins involved in angiogenesis, fibrosis, or inflammation. In this paper, for the first time we describe the miRNA transcription profile in two distinct macrophage populations in MetS-affected cardiac tissue. Although the results are preliminary, the presented data provide a foundation for further studies on intercellular cross-talk/molecular mechanism(s) involved in the regulation of MetS-related cardiac remodeling.

scholarly journals Importance of miR-141-5p and miR-501-5P expression in patients with HBV infection

2021 ◽  
Vol 67 (3) ◽  
pp. 184-189
Author(s):  
Ramin Lak ◽  
Ramin Yaghobi ◽  
Masoud Garshasbi
Keyword(s):  
Expression Profiles ◽  
Rna Extraction ◽  
Diagnostic Value ◽  
Hbv Infection ◽  
Serum Samples ◽  
Transcriptional Modulators ◽  
Patient Groups ◽  
Regulatory Effects ◽  
Noninvasive Biomarkers ◽  
And Control

MicroRNAs (miRNAs) as small RNA and post-transcriptional modulators are shown to have regulatory effects for different cellular activities and pathways, such as metabolism, virus replication and also cell growth. In addition, miRNAs can regulate the replication of the hepatitis B virus (HBV). Therefore, the expression profile of miRNAs was evaluated in HBV-infected patient groups and healthy controls. The expression levels of the following microRNAs (as noninvasive biomarkers) were compared in two experimental (those with various stages of HBV infection) and control groups to evaluate their diagnosis ability: mir141-5p and mir501-5p. RNA extraction was performed for 45 serum samples. The miRCURY LNA™ Universal RT-miRNA-PCR system and miRNA PCR panels were used for measuring microRNA expression profiles. To normalize quantitative values, the endogenous reference by UniSp6 expression was used. Serum mir141-5p and mir501-5 were significant None in patient in different stages of HBV infection(p<0.001) than in controls(p<0.01). Receiver operating characteristic (ROC) curve analyses suggested that serum has mir141-5p and mir501-5p none significant diagnostic value for HBV infection. Results suggest that mir141-5p and mir501-5 can not be used as diagnostic biomarkers for monitoring of HBV infection and other biomarkers in this disease need to be investigated.

scholarly journals Differential expression of microRNAs during root formation in Taxus chinensis var. mairei cultivars

2019 ◽  
Vol 14 (1) ◽  
pp. 97-109
Author(s):  
Yongjun Fei ◽  
Caroline Luo ◽  
Wei Tang
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Root Formation ◽  
Expression Profiles ◽  
Plant Root ◽  
Primary Root ◽  
Taxus Chinensis ◽  
Mirna Expression Profiles ◽  
Root Hair Formation ◽  
First Time

AbstractMicroRNAs (miRNAs) have been shown to play key roles in the regulation of plant growth and development by modifying the expression of their target genes. However, the influence of miRNAs on root formation and development in woody plants, such as Taxus chinensis, remains largely unknown. In the current study, we explored the phytohormone-response and nutrition-response miRNA expression profiles during T. chinensis rooting by quantitative real-time PCR (qPCR). We identified six phytohormone-response miRNAs, namely, miR164a, miR165, miR167a, miR171b, miR319, and miR391, and eight nutrition-response miRNAs, namely, miR169b, miR395a, miR399c, miR408, miR826, miR827, miR857, and miR2111a, that were differentially expressed at different rooting phases of T. chinensis. Using northern blot analysis of the putative target genes of these miRNAs, we detected the relative gene expression changes of the target genes. Taken together, our results suggest that miRNAs are involved in root formation of T. chinensis and that miRNAs may play important regulatory roles in primary root, crown root, and root hair formation by targeting phytohormone and/or nutrition response genes in T. chinensis. For the first time, these results expand our understanding of the molecular mechanisms of plant root formation and development in a conifer species.

scholarly journals Cytokines, miRNAs, and Antioxidants as Combined Non-Invasive Biomarkers for Parkinson's Disease

2021 ◽  
Author(s):  
Amr Ghit ◽  
Hany El Deeb
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Serum Levels ◽  
Serum Samples ◽  
Single Measure ◽  
Locomotor System ◽  
Specificity And Sensitivity ◽  
Noninvasive Biomarkers ◽  
The Many ◽  
Considerable Work

Abstract Background:Parkinson's disease (PD) is one of the most common long-term degenerative disorders of the CNS that primarily affects the human locomotor system. Owing to the heterogeneity of PD etiology and the lack of appropriate diagnostic tests, blood-based biomarkers became the most promising method for diagnosing PD. Even though various biomarkers for PD have been found, their specificity and sensitivity are not optimum when used alone. Therefore, the aim of this study was directed to evaluate changes in a group of sensitive blood-based biomarkers in the same PD patients compared to healthy individuals. Serum samples were collected from 20 PD patients and 15 age-matched healthy controls. We analyzed serum levels of cytokines (IL10, IL12, and TNF-α), α-synuclein proteins, miRNAs (miR-214, miR-221, and miR-141) and antioxidants (UA, PON1, ARE).Results:Our results showed an increase in sera levels of cytokines in PD patients as well as a positive correlation among them. Also, we found a significant increase in sera levels of α-synuclein protein associated with a decrease in miR-214 which regulates its gene expression. Lastly, we observed a decrease in sera levels of miR-221, miR-141, UA, PON1, and ARE, which have a prominent role against oxidative stress.Conclusion:Because of the many etiologies of PD, a single measure is unlikely to become a useful biomarker. Therefore, to correctly predict disease state and progression, a mix of noninvasive biomarkers is required. Although considerable work has to be done, this study sheds light on the role of certain biomarkers in the diagnosis of PD.

scholarly journals Dexamethasone enhances the efficacy of atorvastatin in inhibiting excessively inflammation-induced abnormal angiogenesis by regulating macrophages

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Zhitao Gong ◽  
Daqiang Zhan ◽  
Meng Nie ◽  
Xiaochun Li ◽  
Chuang Gao ◽  
...  
Keyword(s):  
Combined Therapy ◽  
Serum Levels ◽  
Chronic Subdural Haematoma ◽  
High Dose ◽  
Serum Samples ◽  
Drug Treatments ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Related Proteins ◽  
First Time

Abstract Background We have recently showed that atorvastatin (ATO) combined with low dose of dexamethasone (DEX) was more efficacious in treating patients with chronic subdural haematoma (CSDH) than ATO monotherapy. This study was designed to investigate the underlying mechanisms of the improved efficacy of this combined therapy. Methods Mass spectrometry was performed to quantitatively detect drugs in haematoma fluids and serum samples from CSDH patients and also in cultured macrophages after treatment with either ATO alone or in combination with DEX. The differentiation and apoptosis of macrophages were evaluated using flow cytometry. The expression of cytokines, chemokines and angiogenesis-related proteins was evaluated using proteome profile arrays, immunoblots and ELISA, respectively. Results ATO was detected in haematoma fluids and serum samples, whose levels were increased significantly in samples collected from patients treated with both ATO and DEX. ATO was also increased in cultured macrophages treated with ATO and DEX. The numbers of M1-polarized macrophages were higher than the M2 phenotype in the haematoma fluids of patients. Cultured macrophages treated with ATO and DEX had reduced numbers of M1-polarized macrophages, increased numbers of M2-polarized macrophages as compared to monotherapies, and decreased rate of apoptosis induced by high-dose DEX. DEX enhanced the anti-inflammatory and anti-angiogenic activity of ATO by suppressing VEGFA and other inflammatory angiogenic factors. Consistent with the finding, patients responded well to the drug treatments had lower serum levels of VEGFA. Conclusions We have shown for the first time that ATO given orally was detected in CSDH haematoma fluids. DEX enhances the anti-inflammatory and anti-angiogenic effects of ATO, primarily by increasing the presence of ATO in haematoma and macrophages and by regulating the functions of macrophages.

Machine learning-based multiple cancer detections with circulating miRNA profiles in the blood.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3037-3037
Author(s):  
Juntaro Matsuzaki ◽  
Yusuke Yamamoto ◽  
Ouyang Yi ◽  
Sandeep Ayyar ◽  
Ryo Miyajima ◽  
...  
Keyword(s):  
Machine Learning ◽  
Early Detection ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Mirna Expression Profile ◽  
Diagnostic Methods ◽  
Serum Samples ◽  
Multiple Cancer ◽  
Mirna Expression Profiles ◽  
Cancer Types

3037 Background: Early detection of cancer is one of the most important unmet clinical demands. A wide variety of circulating microRNAs (miRNAs) that specifically indicate many types of cancer have been identified, and their miRNA expression profiles are considered as potential biomarkers. Therefore, circulating miRNAs may serve as a non-invasive liquid biopsy diagnostic tool for early detection of many types of cancer. Here, a novel blood-based diagnostic method combined with machine learning techniques is developed using the entire circulating miRNA expression repertoire in serum without prior selection of miRNA marker sets. Methods: To validate this diagnostic method, clinical serum samples from cancer patients with five types of cancer (breast cancer(272), colorectal cancer(239), lung cancer(223), stomach cancer(221) and pancreatic cancer(100)) and 289 non-cancer volunteers were collected. Serum samples were immediately processed and their small RNAs were extracted. The entire miRNA expression profile is analyzed via next generation sequencers. The resulting total miRNA expression profile was used to train machine learning models, including deep learning techniques, without prior selection of miRNAs by human intervention. The machine learning model was trained with a training set to test set ratio of 4:1 and was carefully monitored by 5-fold cross-validation to avoid overfitting. Results: The diagnostic model provided 88% accuracy for all five cancer types (mean). The overall average AUROC was 0.954. Especially for breast cancer, the machine learning model provided 90% accuracy and 91 % sensitivity at 90% specificity. The overall AUROC was 0.966. High sensitivity was obtained regardless of the stage of the cancers, indicating that the possibility of early detection of cancer is kept high. Conclusions: Circulating miRNAs can be informative biomarkers for the earliest cancer detection in combination with machine learning. Unlike other cancer diagnostic methods where only a handful number of biomarkers are considered, this novel miRNA diagnostic platform method that uses machine learning reads a large set of miRNA expression profiles and automatically extracts the specific patterns of miRNA expression for early detection of multiple cancer types. In addition, the main advantage of miRNA-based cancer diagnosis is that they are more sensitive even in the early stages of cancer, compared to other diagnostic methods, such as cell-free DNA diagnostics, where the sensitivity of many types of cancer in the early stages still remains low. This approach could be easily expanded to other cancer types. Given the potential value of early detection in fatal malignancies, further validation studies are justified in future population-based studies. Many cancer research institutes are currently conducting further clinical trials to validate this early cancer diagnosis based on miRNA expression profiles.

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