scholarly journals Androgen receptor is a potential novel prognostic marker and oncogenic target in osteosarcoma with dependence on CDK11

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Yunfei Liao ◽  
Slim Sassi ◽  
Stefan Halvorsen ◽  
Yong Feng ◽  
Jacson Shen ◽  
...  
Keyword(s):  
Cell Growth ◽  
Prognostic Marker ◽  
Cell Lines ◽  
Differentially Expressed Genes ◽  
Transcriptional Activation ◽  
Disease Free Survival ◽  
Bone Cancer ◽  
Differentially Expressed ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells

Abstract Osteosarcoma is the most common bone cancer in children and adolescents. Previously, we have found that cyclin-dependent kinase 11 (CDK11) signaling was essential for osteosarcoma cell growth and survival. Subsequently, CDK11 siRNA gene targeting, expression profiling, and network reconstruction of differentially expressed genes were performed between CDK11 knock down and wild type osteosarcoma cells. Reconstructed network of the differentially expressed genes pointed to the AR as key to CDK11 signaling in osteosarcoma. CDK11 increased transcriptional activation of AR gene in osteosarcoma cell lines. AR protein was highly expressed in various osteosarcoma cell lines and patient tumor tissues. Tissue microarray analysis showed that the disease-free survival rate for patients with high-expression of AR was significantly shorter than for patients with low-expression of AR. In addition, AR gene expression knockdown via siRNA greatly inhibited cell growth and viability. Similar results were found in osteosarcoma cells treated with AR inhibitor. These findings suggest that CDK11 is involved in the regulation of AR pathway and AR can be a potential novel prognostic marker and therapeutic target for osteosarcoma treatment.

scholarly journals PD-L1 Is an Independent Prognostic Marker in Middle Eastern PTC and Its Expression Is Upregulated by BRAFV600E Mutation

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 555
Author(s):  
Abdul K. Siraj ◽  
Sandeep Kumar Parvathareddy ◽  
Poyil Pratheeshkumar ◽  
Sasidharan Padmaja Divya ◽  
Saif S. Al-Sobhi ◽  
...  
Keyword(s):  
Cell Growth ◽  
Prognostic Marker ◽  
Cell Lines ◽  
Braf Mutation ◽  
Middle Eastern ◽  
Disease Free Survival ◽  
Over Expression ◽  
Vitro Analysis ◽  
In Vitro Analysis

PD-L1 inhibition is a promising therapeutic target whose efficacy has been demonstrated in several cancers. Immunohistochemistry was performed to assess PD-L1 protein expression in PTC. We further conducted in vitro analysis to investigate the role of PD-L1 in regulating BRAFV600E in PTC cell lines. PD-L1 over-expression was noted in 32.4% (473/1458) of cases and significantly associated with aggressive clinico-pathological parameters. Importantly, PD-L1 was found to be an independent poorer prognostic marker. We also found PD-L1 to be significantly associated with BRAF mutation and patients with co-existing PD-L1 over-expression and BRAF mutation had a poor disease-free survival compared to patients with BRAF mutation alone. In vitro analysis showed high expression of PD-L1 in BRAF-mutated PTC cell lines compared to a BRAF wild-type cell line. Inhibition of BRAF using vemurafenib induced PD-L1 expression in BRAF-mutated cell lines without affecting cell growth. Knockdown of PD-L1 in BRAF-mutated cell lines significantly decreased the cell growth and induced apoptosis. Our data suggest that PD-L1 might represent a useful prognostic marker in Middle Eastern PTC and PD-L1 inhibition could be a potential therapeutic option for aggressive PTC cancers, such as the tall cell variant, BRAF mutation-positive patients that are unresponsive to standard treatment.

scholarly journals Assessment and Imaging of Intracellular Magnesium in SaOS-2 Osteosarcoma Cells and Its Role in Proliferation

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1376
Author(s):  
Concettina Cappadone ◽  
Emil Malucelli ◽  
Maddalena Zini ◽  
Giovanna Farruggia ◽  
Giovanna Picone ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Magnesium Deficiency ◽  
Acid Synthesis ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
High Concentration ◽  
Proliferating Cells ◽  
Intracellular Magnesium ◽  
In Cells

Magnesium is an essential nutrient involved in many important processes in living organisms, including protein synthesis, cellular energy production and storage, cell growth and nucleic acid synthesis. In this study, we analysed the effect of magnesium deficiency on the proliferation of SaOS-2 osteosarcoma cells. When quiescent magnesium-starved cells were induced to proliferate by serum addition, the magnesium content was 2–3 times lower in cells maintained in a medium without magnesium compared with cells growing in the presence of the ion. Magnesium depletion inhibited cell cycle progression and caused the inhibition of cell proliferation, which was associated with mTOR hypophosphorylation at Serine 2448. In order to map the intracellular magnesium distribution, an analytical approach using synchrotron-based X-ray techniques was applied. When cell growth was stimulated, magnesium was mainly localized near the plasma membrane in cells maintained in a medium without magnesium. In non-proliferating cells growing in the presence of the ion, high concentration areas inside the cell were observed. These results support the role of magnesium in the control of cell proliferation, suggesting that mTOR may represent an important target for the antiproliferative effect of magnesium. Selective control of magnesium availability could be a useful strategy for inhibiting osteosarcoma cell growth.

scholarly journals LncRNA SNHG15 contributes to doxorubicin resistance of osteosarcoma cells through targeting the miR-381-3p/GFRA1 axis

2020 ◽  
Vol 15 (1) ◽  
pp. 871-883
Author(s):  
Jinshan Zhang ◽  
Dan Rao ◽  
Haibo Ma ◽  
Defeng Kong ◽  
Xiaoming Xu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Noncoding Rna ◽  
Xenograft Model ◽  
Inhibitory Effect ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells

AbstractBackgroundOsteosarcoma is a common primary malignant bone cancer. Long noncoding RNA small nucleolar RNA host gene 15 (SNHG15) has been reported to play an oncogenic role in many cancers. Nevertheless, the role of SNHG15 in the doxorubicin (DXR) resistance of osteosarcoma cells has not been fully addressed.MethodsCell Counting Kit-8 assay was conducted to measure the half-maximal inhibitory concentration value of DXR in osteosarcoma cells. Western blotting was carried out to examine the levels of autophagy-related proteins and GDNF family receptor alpha-1 (GFRA1). Quantitative reverse transcription-polymerase chain reaction was performed to determine the levels of SNHG15, miR-381-3p, and GFRA1. The proliferation of osteosarcoma cells was measured by MTT assay. The binding sites between miR-381-3p and SNHG15 or GFRA1 were predicted by Starbase bioinformatics software, and the interaction was confirmed by dual-luciferase reporter assay. Murine xenograft model was established to validate the function of SNHG15 in vivo.ResultsAutophagy inhibitor 3-methyladenine sensitized DXR-resistant osteosarcoma cell lines to DXR. SNHG15 was upregulated in DXR-resistant osteosarcoma tissues and cell lines. SNHG15 knockdown inhibited the proliferation, DXR resistance, and autophagy of osteosarcoma cells. MiR-381-3p was a direct target of SNHG15, and GFRA1 bound to miR-381-3p in osteosarcoma cells. SNHG15 contributed to DXR resistance through the miR-381-3p/GFRA1 axis in vitro. SNHG15 depletion contributed to the inhibitory effect of DXR on osteosarcoma tumor growth through the miR-381-3p/GFRA1 axis in vivo.ConclusionsSNHG15 enhanced the DXR resistance of osteosarcoma cells through elevating the autophagy via targeting the miR-381-3p/GFRA1 axis. Restoration of miR-381-3p expression might be an underlying therapeutic strategy to overcome the DXR resistance of osteosarcoma.

scholarly journals LIM kinase 1 is required for insulin-dependent cell growth of osteosarcoma cell lines

2013 ◽  
Vol 9 (1) ◽  
pp. 103-108 ◽  
Author(s):  
HAI-SHAN ZHANG ◽  
JIAN-WU ZHAO ◽  
HONG WANG ◽  
HAN-YANG ZHANG ◽  
QIU-YE JI ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cell Lines ◽  
Osteosarcoma Cell ◽  
Lim Kinase ◽  
Lim Kinase 1 ◽  
Dependent Cell ◽  
Insulin Dependent

DNA-methylation analysis of differentially expressed genes in fibroblast cell-lines, derived from monozygotic twins discordant for Parkinson’s disease

2020 ◽  
pp. 73-74
Author(s):  
И.Н. Рыболовлев ◽  
И.Н. Власов ◽  
А.Х. Алиева ◽  
П.А. Сломинский ◽  
М.И. Шадрина
Keyword(s):  
Parkinson’S Disease ◽  
Dna Methylation ◽  
Parkinson's Disease ◽  
Cell Lines ◽  
Differentially Expressed Genes ◽  
Regulation Of Gene Expression ◽  
Monozygotic Twins ◽  
Fibroblast Cell ◽  
Differentially Expressed ◽  
Pathogenesis Related

Болезнь Паркинсона (БП) является многофакторным гетерогенным нейродегенеративным заболеванием. Поскольку этиопатогенез БП недостаточно изучен, кроме поиска и анализа изменений на уровне ДНК, необходимо распространить фокус исследований на другие уровни: транскриптом и метилом. Изменения на уровне эпигенома можно исследовать у лиц с идентичной генетической конституцией, такой «моделью» являются дискордантные по этому заболеванию монозиготные близнецы. В исследовании приняло участие 3 пары фенотипически и генотипически монозиготных близнецов русского происхождения; В исследовании приняло участие 3 пары фенотипически и генотипически монозиготных близнецов русского происхождения. БП была уточнена у одного из каждой пары близнецов; длительность течения болезни у близнеца с БП составило по меньшей мере 7 лет.; длительность течения болезни у близнеца с БП составила по меньшей мере 7 лет. Были проанализированы метиломы крови и отобраны точки варьирующегося метилирования. Нами было найдено 8 дифференциально экспрессирующихся генов, которые могут быть дифференциально метилированы. Были выявлены различия между здоровым близнецом и близнецом с БП по уровню метилирования ДНК для ряда этих генов в клеточных линиях фибробластов. Полученные нами данные могут указывать на участие процесса ДНК-метилирования в регуляции транскрипции кандидатных генов-участников патогенеза БП. In recent years it has been convincingly demonstrated that genetic factors play an important role in progression of Parkinson’s disease (PD). Since the etiology of PD has not been elucidated completely yet, it is crucial to shift focus of the research to the broader areas - to dive into investigations of methylome and transcriptome. Epigenetic regulation of gene expression may take part in pathogenesis of PD. Changes in epigenome can be conveniently investigated in case of individuals with almost identical genetic makeup, and monozygotic twins discordant for PD may be such “model”. 3 pairs phenotypically and genotypically monozygous twins of Russian ancestry were enrolled in the study. PD was diagnosed in one of each pair. The disease duration was at least 7 years. Data on blood methylomes was analyzed. Points of variable methylation in blood methylomes were selected. With this approach, 8 differentially expressed genes were found that also may be differentially methylated. Changes in methylation level for some of this genes were found in monozygotic twins discordant for PD fibroblasts cell-lines between healthy and afflicted siblings. Acquired data might suggest participation of DNA-methylation in transcription regulation of PD pathogenesis-related candidate genes.

scholarly journals Antiproliferative Properties of Oleuropein in Human Osteosarcoma Cells

2016 ◽  
Vol 11 (4) ◽  
pp. 1934578X1601100 ◽  
Author(s):  
Jose M. Moran ◽  
Olga Leal-Hernandez ◽  
Maria L. Canal-Macías ◽  
Raul Roncero-Martin ◽  
Rafael Guerrero-Bonmatty ◽  
...  
Keyword(s):  
Cell Lines ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Osteosarcoma Cells ◽  
Probit Regression ◽  
Cytotoxic Effects ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Mg63 Cells ◽  
Human Osteosarcoma Cell

In this study, we evaluated the antiproliferative activity on two human osteosarcoma cell lines (MG-63 and Saos2) of oleuropein, an olive oil compound traditionally found in the Mediterranean diet. Oleuropein exhibited obvious cytotoxic effects on human osteosarcoma cells in a concentration- and time-dependent manner. Statistical analysis of IC50 by the Probit regression method suggested that oleuropein had similar toxic effects on both cell lines tested (IC50 range from 247.4–475.0 μM for MG63 cells and from 798.7–359.9 μM for Saos2 cells).

scholarly journals Regulatory Crosstalk of Doxorubicin, Estradiol and TNFα Combined Treatment in Breast Cancer-derived Cell Lines

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Isar Nassiri ◽  
Alberto Inga ◽  
Erna Marija Meškytė ◽  
Federica Alessandrini ◽  
Yari Ciribilli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Differentially Expressed Genes ◽  
Combination Treatment ◽  
Combined Treatment ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Transcriptional Responses ◽  
Predisposing Factor ◽  
Inflammatory Microenvironment

Abstract We present a new model of ESR1 network regulation based on analysis of Doxorubicin, Estradiol, and TNFα combination treatment in MCF-7. We used Doxorubicin as a therapeutic agent, TNFα as marker and mediator of an inflammatory microenvironment and 17β-Estradiol (E2) as an agonist of Estrogen Receptors, known predisposing factor for hormone-driven breast cancer, whose pharmacological inhibition reduces the risk of breast cancer recurrence. Based on the results of transcriptomics analysis, we found 71 differentially expressed genes that are specific for the combination treatment with Doxorubicin + Estradiol + TNFα in comparison with single or double treatments. The responsiveness to the triple treatment was examined for seven genes by qPCR, of which six were validated, and then extended to four additional cell lines differing for p53 and/or ER status. The results of differential regulation enrichment analysis highlight the role of the ESR1 network that included 36 of 71 specific differentially expressed genes. We propose that the combined activation of p53 and NF-kB transcription factors significantly influences ligand-dependent, ER-driven transcriptional responses, also of the ESR1 gene itself. These results provide a model of coordinated interaction of TFs to explain the Doxorubicin, E2 and TNFα induced repression mechanisms.

MicroRNA-211-5p promotes apoptosis and inhibits the migration of osteosarcoma cells by targeting proline-rich protein PRR11

2020 ◽  
Vol 98 (2) ◽  
pp. 258-266 ◽  
Author(s):  
Dandan Song ◽  
Kun Yang ◽  
Wei Wang ◽  
Run Tian ◽  
Haoyu Wang ◽  
...  
Keyword(s):  
Young Adults ◽  
Survival Rate ◽  
Personalized Medicine ◽  
Cell Lines ◽  
Clinical Samples ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Expression Levels ◽  
Proline Rich Protein

Osteosarcoma remains fatal in adolescents and young adults, with a 5-year survival rate of less than 20%. However, the details for mechanisms that regulate osteosarcoma metastasis are poorly understood. We analyzed the expression levels of miR-211-5p in clinical samples of osteosarcoma as well as cell lines, and found that the expression of miR-211-5p was reduced in osteosarcoma. Moreover, induction of miR-211-5p in several osteosarcoma cell lines dramatically inhibited their migration and invasiveness. Furthermore, miR-211-5p overexpression led to a significant increase in the apoptosis of osteosarcoma cell. Importantly, our in vivo xenograft experiments showed that miR-211-5p strongly inhibits tumorigenesis. Additionally, functional experiments demonstrated that miR-211-5p suppresses the expression of proline-rich protein 11 (PRR11) by directly binding to the 3′ region of PRR11 mRNA. Moreover, we showed that PRR11 overexpression attenuated the increase of apoptosis and decreased migration and invasiveness when the upstream miR-211-5p was overexpressed. Our data provide new insights into the mechanisms that regulate osteosarcoma metastasis, and novel potential pharmaceutical targets for personalized medicine.

scholarly journals 3357 TL1 Team Approach to Using a Combination of Ganglioside 2 and 3 as an Immunoaffinity Target for Circulating Osteosarcoma Cell Detection

2019 ◽  
Vol 3 (s1) ◽  
pp. 134-135
Author(s):  
Henrietta Fasanya ◽  
Pablo Joaquin Dopico ◽  
Zachary J. Yeager ◽  
Hugh Fan ◽  
Dietmar W. Siemann
Keyword(s):  
Flow Cytometry ◽  
Cell Surface ◽  
Cell Lines ◽  
Treatment Efficacy ◽  
Capture Efficiency ◽  
Cell Detection ◽  
Surface Markers ◽  
Osteosarcoma Cell ◽  
Cell Surface Markers ◽  
Osteosarcoma Cells

OBJECTIVES/SPECIFIC AIMS: The objective of our collaboration is to develop a strong trans-disciplinary team consisting of microfluidics engineers, cancer biologists, and clinicians, to identify a universal marker to detect circulating osteosarcoma cells (COC) using microfluidic devices. Our goals are 3 fold: 1) Identify cell surface markers unique to osteosarcoma (OS) for COC isolation, 2) Develop a Geometrically Enhanced Mixing (GEM) device to isolate COCs, and 3) Evaluate the efficacy of GEM device to detect COCs in patients with OS. The long term goal of this collaboration is to utilize this cell detection approach to evaluate treatment efficacy and correlate the presence of circulating osteosarcoma cells with metastatic incidence. METHODS/STUDY POPULATION: In this phase of our study, we have identified an abundant and conserved cell surface marker across a panel of OS cell lines. Flow cytometry was used to evaluate the relative expression of Epithelial Cell Adhesion Molecule (EpCAM), and Ganglioside 2 or/and 3 (GD2/3) on a panel of OS cell lines. An antibody coated GEM microfluidic device is used to affirm the efficacy of GD2/3 to capture COCs. Further capture studies will be conducted using OS cell spiked blood samples. Analysis of variance (ANOVA) will be used to determine any significant difference in capture efficiency between EpCAM, GD2/3 cell surface markers. RESULTS/ANTICIPATED RESULTS: Our results demonstrate that EpCAM is not a suitable marker for COC detection. Results from our flow cytometry studies demonstrate that GD2/3 expression is significantly higher than EpCAM expression, across all OS cell lines within our panel. The cell capture efficiency strongly correlates with the cell surface expression data obtained from flow cytometry analysis. DISCUSSION/SIGNIFICANCE OF IMPACT: OS is the most common primary bone tumor and the third leading cause of pediatric cancer deaths. At diagnosis, 80% of patients will present with metastasis, however only 20% of these cases are clinically detectable. Innovative strategies to identify patients at risk of metastasis would allow for stratification of intervention therapies. Liquid biopsies are a novel alternative to current diagnostic imaging systems to monitor metastatic incidence and treatment efficacy. The detection of circulating tumor cells (CTCs) through routine blood sampling has the potential to be used clinically for earlier detection, monitoring the treatment of metastatic cancers and surveying the effect of therapeutic interventions on metastasis. To date, the majority of the studies on CTCs have evaluated their presence in carcinomas. Although sarcomas are rare, they generally have a poorer prognosis. This study will address one of the unmet medical needs in the field of CTC detection; the identification of cell surface OS makers to improve binding specificity, increase purity, and maintain a high capture efficiency.

Sign in / Sign up

Export Citation Format

Share Document