Dissecting Intra-Tumor Heterogeneity by the Analysis of Copy Number Variations in Single Cells: The Neuroblastoma Case Study.

Abstract:

:Tumors often show intra-tumor heterogeneity because of genotypic differences between all the cells that compose it and that derive from it. Recent studies have shown significant aspects of neuroblastoma heterogeneity that may affect the diagnostic-therapeutic strategy. Therefore, we developed a laboratory protocol, based on the combination of the advanced dielectrophoresis-based array technology and next-generation sequencing to identify and sort single cells individually and carry out their copy number variants analysis. The aim was to evaluate the cellular heterogeneity, avoiding overestimation or underestimation errors, due to a bulk analysis of the sample. We tested the above-mentioned protocol on two neuroblastoma cell lines, SK-N-BE(2)-C and IMR-32. The presence of several gain or loss chromosomal regions, in both cell lines, shows a high heterogeneity of the copy number variants status of the single tumor cells, even if they belong to an immortalized cell line. This finding confirms that each cell can potentially accumulate different alterations that can modulate its behavior. The laboratory protocol proposed herein provides a tool able to identify prevalent behaviors, and at the same time highlights the presence of particular clusters that deviate from them. Finally, it could be applicable to many other types of cancer.

journal_name

Int J Mol Sci

authors

Cariati F,Borrillo F,Shankar V,Nunziato M,D'Argenio V,Tomaiuolo R

doi

10.3390/ijms20040893

subject

Has Abstract

pub_date

2019-02-19 00:00:00

issue

4

issn

1422-0067

pii

ijms20040893

journal_volume

20

pub_type

杂志文章
  • Effect of Clotting Duration and Temperature on BDNF Measurement in Human Serum.

    abstract::Brain-derived neurothrophic factor (BDNF) is a neurotrophin expressed in different tissues and cells, including neurons, endothelial cells, leukocytes, megakaryocytes and platelets. Modifications of BDNF in plasma and/or in serum are associated with neurodegenerative and psychiatric disorders, cardiovascular diseases,...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms18091987

    authors: Amadio P,Sandrini L,Ieraci A,Tremoli E,Barbieri SS

    更新日期:2017-09-15 00:00:00

  • Ultrasound assessment of carotid plaque echogenicity response to statin therapy: a systematic review and meta-analysis.

    abstract:OBJECTIVE:To evaluate in a systematic review and meta-analysis model the effect of statin therapy on carotid plaque echogenicity assessed by ultrasound. METHODS:We have systematically searched electronic databases (PubMed, MEDLINE, EMBASE and Cochrane Center Register) up to April, 2015, for studies evaluating the effe...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,meta分析,评审

    doi:10.3390/ijms160510734

    authors: Ibrahimi P,Jashari F,Bajraktari G,Wester P,Henein MY

    更新日期:2015-05-12 00:00:00

  • The Possible Importance of β3 Integrins for Leukemogenesis and Chemoresistance in Acute Myeloid Leukemia.

    abstract::Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy where the immature leukemia cells communicate with neighboring cells through constitutive cytokine release and through their cell surface adhesion molecules. The primary AML cells express various integrins. These heterodimeric molecules containing an...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms19010251

    authors: Johansen S,Brenner AK,Bartaula-Brevik S,Reikvam H,Bruserud Ø

    更新日期:2018-01-15 00:00:00

  • Immune Checkpoint Inhibitors in Esophageal Cancers: are we Finally Finding the Right Path in the Mist?

    abstract::Esophageal cancer remains a challenging disease due to limited treatment options and poor prognosis. In recent years, immune checkpoint inhibitors (ICI) have been proven to be safe and effective in the treatment of highly lethal malignancies, such as non-small cell lung cancer and melanoma. Recent clinical trials also...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms21051658

    authors: Vivaldi C,Catanese S,Massa V,Pecora I,Salani F,Santi S,Lencioni M,Vasile E,Falcone A,Fornaro L

    更新日期:2020-02-28 00:00:00

  • Modeling the Effect of Hypoxia and DNA Repair Inhibition on Cell Survival After Photon Irradiation.

    abstract::Mechanistic approaches to modeling the effects of ionizing radiation on cells are on the rise, promising a better understanding of predictions and higher flexibility concerning conditions to be accounted for. In this work we modified and extended a previously published mechanistic model of cell survival after photon i...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20236054

    authors: Liew H,Klein C,Zenke FT,Abdollahi A,Debus J,Dokic I,Mairani A

    更新日期:2019-11-30 00:00:00

  • Injectable Systems for Intra-Articular Delivery of Mesenchymal Stromal Cells for Cartilage Treatment: A Systematic Review of Preclinical and Clinical Evidence.

    abstract::Stem cell-based therapy is a promising approach to treat cartilage lesions and clinical benefits have been reported in a number of studies. However, the efficacy of cell injection procedures may be impaired by cell manipulation and damage as well as by cell dissemination to non-target tissues. To overcome such issues,...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms19113322

    authors: Roffi A,Nakamura N,Sanchez M,Cucchiarini M,Filardo G

    更新日期:2018-10-25 00:00:00

  • Microglial Pro-Inflammatory and Anti-Inflammatory Phenotypes Are Modulated by Translocator Protein Activation.

    abstract::A key role of the mitochondrial Translocator Protein 18 KDa (TSPO) in neuroinflammation has been recently proposed. However, little is known about TSPO-activated pathways underlying the modulation of reactive microglia. In the present work, the TSPO activation was explored in an in vitro human primary microglia model ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20184467

    authors: Pozzo ED,Tremolanti C,Costa B,Giacomelli C,Milenkovic VM,Bader S,Wetzel CH,Rupprecht R,Taliani S,Settimo FD,Martini C

    更新日期:2019-09-10 00:00:00

  • Potential of the NKG2D/NKG2DL Axis in NK Cell-Mediated Clearance of the HIV-1 Reservoir.

    abstract::Viral persistency in latently infected CD4+ T cells despite antiretroviral therapy (ART) represents a major drawback in the fight against HIV-1. Efforts to purge latent HIV-1 have been attempted using latency reversing agents (LRAs) that activate expression of the quiescent virus. However, initial trials have shown th...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms20184490

    authors: Desimio MG,Covino DA,Doria M

    更新日期:2019-09-11 00:00:00

  • Antibacterial activity of the alkaloid-enriched extract from Prosopis juliflora pods and its influence on in vitro ruminal digestion.

    abstract::The purpose of this study was to assess the in vitro antimicrobial activity of alkaloid-enriched extracts from Prosopis juliflora (Fabaceae) pods in order to evaluate them as feed additives for ruminants. As only the basic chloroformic extract (BCE), whose main constituents were juliprosopine (juliflorine), prosoflori...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms14048496

    authors: Dos Santos ET,Pereira ML,da Silva CF,Souza-Neta LC,Geris R,Martins D,Santana AE,Barbosa LC,Silva HG,Freitas GC,Figueiredo MP,de Oliveira FF,Batista R

    更新日期:2013-04-17 00:00:00

  • Zebrafish as a Model for the Study of Microvascular Complications of Diabetes and Their Mechanisms.

    abstract::Diabetes mellitus (DM) is a crucial metabolic disease that leads to severe disorders. These include macrovascular complications such as myocardial infarction, stroke, and peripheral artery disease and microvascular complications including diabetic nephropathy, neuropathy, and retinopathy. Diabetes mellitus, along with...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms18092002

    authors: Heckler K,Kroll J

    更新日期:2017-09-19 00:00:00

  • Homogenized finite element analysis on effective elastoplastic mechanical behaviors of composite with imperfect interfaces.

    abstract::A three-dimensional (3D) representative volume element (RVE) model was developed for analyzing effective mechanical behavior of fiber-reinforced ceramic matrix composites with imperfect interfaces. In the model, the fiber is assumed to be perfectly elastic until its tensile strength, and the ceramic material is modele...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms151223389

    authors: Jiang WG,Zhong RZ,Qin QH,Tong YG

    更新日期:2014-12-16 00:00:00

  • Application of the Movable Type Free Energy Method to the Caspase-Inhibitor BindingAffinity Study.

    abstract::Many studies have provided evidence suggesting that caspases not only contribute to the neurodegeneration associated with Alzheimer's disease (AD) but also play essential roles in promoting the underlying pathology of this disease. Studies regarding the caspase inhibition draw researchers' attention through time due t...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20194850

    authors: Xue S,Liu H,Zheng Z

    更新日期:2019-09-29 00:00:00

  • Irradiation-Induced Upregulation of miR-711 Inhibits DNA Repair and Promotes Neurodegeneration Pathways.

    abstract::Radiotherapy for brain tumors induces neuronal DNA damage and may lead to neurodegeneration and cognitive deficits. We investigated the mechanisms of radiation-induced neuronal cell death and the role of miR-711 in the regulation of these pathways. We used in vitro and in vivo models of radiation-induced neuronal cell...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21155239

    authors: Sabirzhanov B,Makarevich O,Barrett JP,Jackson IL,Glaser EP,Faden AI,Stoica BA

    更新日期:2020-07-23 00:00:00

  • MicroRNA-29a Mitigates Subacromial Bursa Fibrosis in Rotator Cuff Lesion with Shoulder Stiffness.

    abstract::Rotator cuff lesion with shoulder stiffness is a major cause of shoulder pain and motionlessness. Subacromial bursa fibrosis is a prominent pathological feature of the shoulder disorder. MicroRNA-29a (miR-29a) regulates fibrosis in various tissues; however, the miR-29a action to subacromial bursa fibrosis remains elus...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20225742

    authors: Ko JY,Lian WS,Tsai TC,Chen YS,Hsieh CK,Kuo CW,Wang FS

    更新日期:2019-11-15 00:00:00

  • Regulation of Chemokine-Receptor Interactions and Functions.

    abstract::Inflammation is the body's response to injury or infection. As early as 2000 years ago, the Roman encyclopaedist Aulus Cornelius Celsus recognised four cardinal signs of this response-redness, heat, swelling and pain; a fifth sign is loss of function.[...]. ...

    journal_title:International journal of molecular sciences

    pub_type: 社论

    doi:10.3390/ijms18112415

    authors: Stone MJ

    更新日期:2017-11-14 00:00:00

  • Enzymatic Biotransformation of Balloon Flower Root Saponins into Bioactive Platycodin D by Deglucosylation with Caldicellulosiruptor bescii β-Glucosidase.

    abstract::Platycodin D (PD), a major saponin (platycoside) in Platycodi radix (balloon flower root), has higher pharmacological activity than the other major platycosides; however, its content in the plant root is only approximately 10% (w/w) and the productivities of PD by several enzymes are still too low for industrial appli...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20163854

    authors: Kil TG,Kang SH,Kim TH,Shin KC,Oh DK

    更新日期:2019-08-07 00:00:00

  • In Vitro Inhibition of Phosphodiesterase 3B (PDE 3B) by Anthocyanin-Rich Fruit Juice Extracts and Selected Anthocyanins.

    abstract::Phosphodiesterases (PDEs) are essential enzymes for the regulation of pathways mediated by cyclic adenosine monophosphate (cAMP). Secondary plant compounds like anthocyanins (ACs) can inhibit PDE activity and, consequently, may be beneficial for lipid metabolism. This study investigated 18 AC-rich juice extracts and p...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21186934

    authors: Göttel C,Niesen S,Daub V,Werle T,Bakuradze T,Winterhalter P,Richling E

    更新日期:2020-09-21 00:00:00

  • Differential Effects of a Full and Biased Ghrelin Receptor Agonist in a Mouse Kindling Model.

    abstract::The ghrelin system has received substantial recognition as a potential target for novel anti-seizure drugs. Ghrelin receptor (ghrelin-R) signaling is complex, involving Gαq/11, Gαi/o, Gα12/13, and β-arrestin pathways. In this study, we aimed to deepen our understanding regarding signaling pathways downstream the ghrel...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20102480

    authors: Buckinx A,Van Den Herrewegen Y,Pierre A,Cottone E,Ben Haj Salah K,Fehrentz JA,Kooijman R,De Bundel D,Smolders I

    更新日期:2019-05-20 00:00:00

  • Transcriptome Sequencing Reveals the Differentially Expressed lncRNAs and mRNAs Involved in Cryoinjuries in Frozen-Thawed Giant Panda (Ailuropoda melanoleuca) Sperm.

    abstract::Sperm cryopreservation and artificial insemination are important methods for giant panda breeding and preservation of extant genetic diversity. Lower conception rates limit the use of artificial insemination with frozen-thawed giant panda sperm, due to the lack of understanding of the cryodamaging or cryoinjuring mech...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms19103066

    authors: Ran MX,Li Y,Zhang Y,Liang K,Ren YN,Zhang M,Zhou GB,Zhou YM,Wu K,Wang CD,Huang Y,Luo B,Qazi IH,Zhang HM,Zeng CJ

    更新日期:2018-10-08 00:00:00

  • What Is the Evolutionary Fingerprint in Neutrophil Granulocytes?

    abstract::Over the years of evolution, thousands of different animal species have evolved. All these species require an immune system to defend themselves against invading pathogens. Nevertheless, the immune systems of different species are obviously counteracting against the same pathogen with different efficiency. Therefore, ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms21124523

    authors: Fingerhut L,Dolz G,de Buhr N

    更新日期:2020-06-25 00:00:00

  • Resveratrol and Its Effects on the Vascular System.

    abstract::Resveratrol, the phenolic substance isolated initially from Veratrum grandiflorum and richly present in grapes, wine, peanuts, soy, and berries, has been attracting attention of scientists and medical doctors for many decades. Herein, we review its effects on the vascular system. Studies utilizing cell cultures and pr...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms20071523

    authors: Breuss JM,Atanasov AG,Uhrin P

    更新日期:2019-03-27 00:00:00

  • cGMP Imaging in Brain Slices Reveals Brain Region-Specific Activity of NO-Sensitive Guanylyl Cyclases (NO-GCs) and NO-GC Stimulators.

    abstract::Impaired NO-cGMP signaling has been linked to several neurological disorders. NO-sensitive guanylyl cyclase (NO-GC), of which two isoforms-NO-GC1 and NO-GC2-are known, represents a promising drug target to increase cGMP in the brain. Drug-like small molecules have been discovered that work synergistically with NO to s...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms19082313

    authors: Peters S,Paolillo M,Mergia E,Koesling D,Kennel L,Schmidtko A,Russwurm M,Feil R

    更新日期:2018-08-07 00:00:00

  • Gold Nanopeanuts as Prospective Support for Cisplatin in Glioblastoma Nano-Chemo-Radiotherapy.

    abstract::Herein, we propose newly designed and synthesized gold nanopeanuts (Au NPes) as supports for cisplatin (cPt) immobilization, dedicated to combined glioblastoma nano-chemo-radiotherapy. Au NPes offer a large active surface, which can be used for drugs immobilization. Transmission electron microscopy (TEM) revealed that...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21239082

    authors: Depciuch J,Miszczyk J,Maximenko A,Zielinski PM,Rawojć K,Panek A,Olko P,Parlinska-Wojtan M

    更新日期:2020-11-29 00:00:00

  • Increased exosomal microRNA-21 and microRNA-146a levels in the cervicovaginal lavage specimens of patients with cervical cancer.

    abstract::Well-run screening programs for cervical cancer in the population at risk have been shown to result in a sharp decrease in the incidence and mortality of cervical cancer in a number of large populations. Expression patterns of a recently identified biomarker family, microRNA, appear to be characteristic of tumor type ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms15010758

    authors: Liu J,Sun H,Wang X,Yu Q,Li S,Yu X,Gong W

    更新日期:2014-01-08 00:00:00

  • Effect of Bilastine on Diabetic Nephropathy in DBA2/J Mice.

    abstract::Diabetic nephropathy is an unmet therapeutic need, and the search for new therapeutic strategies is warranted. Previous data point to histamine H1 receptor as a possible target for glomerular dysfunction associated with long term hyperglycaemia. Therefore, this study investigated the effects of the H1 receptor antagon...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20102554

    authors: Verta R,Grange C,Gurrieri M,Borga S,Nardini P,Argenziano M,Ghè C,Cavalli R,Benetti E,Miglio G,Bussolati B,Pini A,Rosa AC

    更新日期:2019-05-24 00:00:00

  • Fanconi-Bickel Syndrome: A Review of the Mechanisms That Lead to Dysglycaemia.

    abstract::Accumulation of glycogen in the kidney and liver is the main feature of Fanconi-Bickel Syndrome (FBS), a rare disorder of carbohydrate metabolism inherited in an autosomal recessive manner due to SLC2A2 gene mutations. Missense, nonsense, frame-shift (fs), in-frame indels, splice site, and compound heterozygous varian...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms21176286

    authors: Sharari S,Abou-Alloul M,Hussain K,Ahmad Khan F

    更新日期:2020-08-31 00:00:00

  • Reactive oxygen species enhance TLR10 expression in the human monocytic cell line THP-1.

    abstract::We investigated TLR10 expression in human monocytes, THP-1 cells, cultured in hypoxia (3% O(2)). Levels of both TLR10 mRNA and protein in THP-1 cells cultured in hypoxia were significantly higher than those cultured in normoxia (20% O(2)). We examined intracellular reactive oxygen species (ROS) content in hypoxic cell...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms11103769

    authors: Kim D,Kim YJ,Koh HS,Jang TY,Park HE,Kim JY

    更新日期:2010-09-29 00:00:00

  • Structural and Functional Annotation of Transposable Elements Revealed a Potential Regulation of Genes Involved in Rubber Biosynthesis by TE-Derived siRNA Interference in Hevea brasiliensis.

    abstract::The natural rubber biosynthetic pathway is well described in Hevea, although the final stages of rubber elongation are still poorly understood. Small Rubber Particle Proteins and Rubber Elongation Factors (SRPPs and REFs) are proteins with major function in rubber particle formation and stabilization. Their correspond...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21124220

    authors: Wu S,Guyot R,Bocs S,Droc G,Oktavia F,Hu S,Tang C,Montoro P,Leclercq J

    更新日期:2020-06-13 00:00:00

  • The Ubiquitin Proteasome System in Neuromuscular Disorders: Moving Beyond Movement.

    abstract::Neuromuscular disorders (NMDs) affect 1 in 3000 people worldwide. There are more than 150 different types of NMDs, where the common feature is the loss of muscle strength. These disorders are classified according to their neuroanatomical location, as motor neuron diseases, peripheral nerve diseases, neuromuscular junc...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms21176429

    authors: Bachiller S,Alonso-Bellido IM,Real LM,Pérez-Villegas EM,Venero JL,Deierborg T,Armengol JÁ,Ruiz R

    更新日期:2020-09-03 00:00:00

  • Human NANOS1 Represses Apoptosis by Downregulating Pro-Apoptotic Genes in the Male Germ Cell Line.

    abstract::While two mouse NANOS paralogues, NANOS2 and NANOS3, are crucial for maintenance of germ cells by suppression of apoptosis, the mouse NANOS1 paralogue does not seem to regulate these processes. Previously, we described a human NANOS1 p.[(Pro34Thr);(Ser83del)] mutation associated with the absence of germ cells in semin...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21083009

    authors: Janecki DM,Ilaslan E,Smialek MJ,Sajek MP,Kotecki M,Ginter-Matuszewska B,Krainski P,Jaruzelska J,Kusz-Zamelczyk K

    更新日期:2020-04-24 00:00:00