scholarly journals Photo-Magnetic Irradiation-Mediated Multimodal Therapy of Neuroblastoma Cells Using a Cluster of Multifunctional Nanostructures

Nanomaterials ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 774 ◽  
Author(s):  
Rohini Atluri ◽  
Rahul Atmaramani ◽  
Gamage Tharaka ◽  
Thomas McCallister ◽  
Jian Peng ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Multimodal Therapy ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Modest Improvement ◽  
Cell Destruction ◽  
Multifunctional Nanostructures ◽  
Viable Approach ◽  
Post Modification ◽  
Multimodal Therapeutic Strategy

The use of high intensity chemo-radiotherapies has demonstrated only modest improvement in the treatment of high-risk neuroblastomas. Moreover, undesirable drug specific and radiation therapy-incurred side effects enhance the risk of developing into a second cancer at a later stage. In this study, a safer and alternative multimodal therapeutic strategy involving simultaneous optical and oscillating (AC, Alternating Current) magnetic field stimulation of a multifunctional nanocarrier system has successfully been implemented to guide neuroblastoma cell destruction. This novel technique permitted the use of low-intensity photo-magnetic irradiation and reduced the required nanoparticle dose level. The combination of released cisplatin from the nanodrug reservoirs and photo-magnetic coupled hyperthermia mediated cytotoxicity led to the complete ablation of the B35 neuroblastoma cells in culture. Our study suggests that smart nanostructure-based photo-magnetic hybrid irradiation is a viable approach to remotely guide neuroblastoma cell destruction, which may be adopted in clinical management post modification to treat aggressive cancers.

Hydroxyurea induces a senescent, non-malignant, immunogenic state in neuroblastoma cells – a new therapeutic strategy?

2010 ◽  
Vol 222 (03) ◽  
Author(s):  
S Taschner-Mandl ◽  
A Kowalska ◽  
H Binder ◽  
D Rieder ◽  
Z Trajanoski ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Neuroblastoma Cells

p-Trifluoroacetophenone Oxime Ester Derivatives: Synthesis, Antimicrobial and Cytotoxic Evaluation and Molecular Modeling Studies

2020 ◽  
Vol 17 (2) ◽  
pp. 169-183 ◽  
Author(s):  
İrem Bozbey ◽  
Suat Sari ◽  
Emine Şalva ◽  
Didem Kart ◽  
Arzu Karakurt
Keyword(s):  
Molecular Modeling ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Cytotoxic Agents ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Modeling Studies ◽  
Broth Microdilution Method ◽  
Molecular Modeling Studies

Background: Azole antifungals are among the first-line drugs clinically used for the treatment of systemic candidiasis, a deadly type of fungal infection that threatens mostly immunecompromised and hospitalized patients. Some azole derivatives were also reported to have antiproliferative effects on cancer cells. Objective: In this study, 1-(4-trifluoromethylphenyl)-2-(1H-imidazol-1-yl)ethanone (3), its oxime (4), and a series of its novel oxime ester derivatives (5a-v) were synthesized and tested for their in vitro antimicrobial activities against certain ATCC standard strains of Candida sp. fungi and bacteria. The compounds were also tested for their cytotoxic effects against mouse fibroblast and human neuroblastoma cell lines. Molecular modeling studies were performed to provide insights into their possible mechanisms for antifungal and antibacterial actions. Methods: The compounds were synthesized by the reaction of various oximes with acyl chlorides. Antimicrobial activity of the compounds was determined according to the broth microdilution method. For the determination of cytotoxic effect, we used MTS assay. Molecular docking and QM/MM studies were performed to predict the binding mechanisms of the active compounds in the catalytic site of C. albicans CYP51 (CACYP51) and S. aureus flavohemoglobin (SAFH), the latter of which was created via homology modeling. Results: 5d, 5l, and 5t showed moderate antifungal activity against C. albicans, while 3, 5c, and 5r showed significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Most of the compounds showed approximately 40-50% inhibition against the human neuroblastoma cells at 100 µM. In this line, 3 was the most potent with an IC50 value of 82.18 μM followed by 5a, 5o, and 5t. 3 and 5a were highly selective to the neuroblastoma cells. Molecular modelling results supported the hypothesis that our compounds were inhibitors of CAYP51 and SAFH. Conclusion: This study supports that oxime ester derivatives may be used for the development of new antimicrobial and cytotoxic agents.

scholarly journals Plasticity in Neuroblastoma Cell Identity Defines a Noradrenergic-to-Mesenchymal Transition (NMT)

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2904
Author(s):  
Margot Gautier ◽  
Cécile Thirant ◽  
Olivier Delattre ◽  
Isabelle Janoueix-Lerosey
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Biochemical Properties ◽  
Poor Overall Survival ◽  
Cell Identity ◽  
Mesenchymal Transition ◽  
Neuroblastoma Cell Lines

Neuroblastoma, a pediatric cancer of the peripheral sympathetic nervous system, is characterized by an important clinical heterogeneity, and high-risk tumors are associated with a poor overall survival. Neuroblastoma cells may present with diverse morphological and biochemical properties in vitro, and seminal observations suggested that interconversion between two phenotypes called N-type and S-type may occur. In 2017, two main studies provided novel insights into these subtypes through the characterization of the transcriptomic and epigenetic landscapes of a panel of neuroblastoma cell lines. In this review, we focus on the available data that define neuroblastoma cell identity and propose to use the term noradrenergic (NOR) and mesenchymal (MES) to refer to these identities. We also address the question of transdifferentiation between both states and suggest that the plasticity between the NOR identity and the MES identity defines a noradrenergic-to-mesenchymal transition, reminiscent of but different from the well-established epithelial-to-mesenchymal transition.

scholarly journals Regulation of c-myb expression in human neuroblastoma cells during retinoic acid-induced differentiation.

1988 ◽  
Vol 8 (4) ◽  
pp. 1677-1683 ◽  
Author(s):  
C J Thiele ◽  
P S Cohen ◽  
M A Israel
Keyword(s):  
Retinoic Acid ◽  
Fetal Development ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Hematopoietic Lineage ◽  
Specific Manner ◽  
Neuroblastoma Cell Lines

We detected expression of the c-myb proto-oncogene, which was initially thought to be expressed in a tissue-specific manner in cells of hematopoietic lineage, in human tissues of neuronal origin. Since the level of c-myb expression declined during fetal development, we studied the regulation of its expression in human neuroblastoma cell lines induced to differentiate by retinoic acid. The expression of c-myb declined during the maturation of neuroblastoma cells, and this change was mediated by a decrease in c-myb transcription.

scholarly journals Transplantation of Human Neuroblastoma Cells, Catecholaminergic and Non-Catecholaminergic: Effects on Rotational Behavoir in Parkinson's Rat Model

1992 ◽  
Vol 3 (2-3) ◽  
pp. 139-150 ◽  
Author(s):  
Jacob S. Manaster ◽  
Tony Feuerman ◽  
C. Patrick Reynolds ◽  
Charles H. Markham
Keyword(s):  
Cell Lines ◽  
Rat Model ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Neuroblastoma Cell Line ◽  
Rotational Behavior ◽  
Human Neuroblastoma ◽  
Donor Cells ◽  
Catecholamine Fluorescence ◽  
Motor Improvement

Cultured human catecholaminergic and noncatecholaminergic donor cells were used in neural transplantation experiments in a rat model of Parkinson's disease. Using two different human catecholaminergic neuroblastoma cell lines, one control non-catecholaminergic neuroblastoma cell line, and one sham control (tissue culture medium), transplants were made into the striatum using a modified Ungerstedt hemiparkinsonian rat model. Significant decreases in apomorphine-induced rotational behavior were produced by two of three catecholaminergic cell lines. Grafted cells staining positively for tyrosine hydroxylase (TH) and catecholamine fluorescence indicated viable catecholamine activity in the two cell lines which produced reductions in rotational behavior. Catecholamine fluorescence was not detected in either of the two controls. These data suggest a link between catecholamine secretion by transplanted cells and motor improvement using a rat rotational behavior model.

Tissue transglutaminase and apoptosis: sense and antisense transfection studies with human neuroblastoma cells

1994 ◽  
Vol 14 (10) ◽  
pp. 6584-6596
Author(s):  
G Melino ◽  
M Annicchiarico-Petruzzelli ◽  
L Piredda ◽  
E Candi ◽  
V Gentile ◽  
...  
Keyword(s):  
Cell Death ◽  
Structural Changes ◽  
Tissue Transglutaminase ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Neuroblastoma Cell Line ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Transfected Cells ◽  
Protein Levels

In this report, we show that the overexpression of tissue transglutaminase (tTG) in the human neuroblastoma cell line SK-N-BE(2) renders these neural crest-derived cells highly susceptible to death by apoptosis. Cells transfected with a full-length tTG cDNA, under the control of a constitutive promoter, show a drastic reduction in proliferative capacity paralleled by a large increase in cell death rate. The dying tTG-transfected cells exhibit both cytoplasmic and nuclear changes characteristic of cells undergoing apoptosis. The tTG-transfected cells express high Bcl-2 protein levels as well as phenotypic neural cell adhesion molecule markers (NCAM and neurofilaments) of cells differentiating along the neuronal pathway. In keeping with these findings, transfection of neuroblastoma cells with an expression vector containing segments of the human tTG cDNA in antisense orientation resulted in a pronounced decrease of both spontaneous and retinoic acid (RA)-induced apoptosis. We also present evidence that (i) the apoptotic program of these neuroectodermal cells is strictly regulated by RA and (ii) cell death by apoptosis in the human neuroblastoma SK-N-BE(2) cells preferentially occurs in the substrate-adherent phenotype. For the first time, we report here a direct effect of tTG in the phenotypic maturation toward apoptosis. These results indicate that the tTG-dependent irreversible cross-linking of intracellular protein represents an important biochemical event in the induction of the structural changes featuring cells dying by apoptosis.

scholarly journals Integrated proximal proteomics reveals IRS2 as a determinant of cell survival in ALK-driven neuroblastoma

2018 ◽  
Vol 11 (557) ◽  
pp. eaap9752 ◽  
Author(s):  
Kristina B. Emdal ◽  
Anna-Kathrine Pedersen ◽  
Dorte B. Bekker-Jensen ◽  
Alicia Lundby ◽  
Shana Claeys ◽  
...  
Keyword(s):  
Cell Survival ◽  
Kinase Inhibitors ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Adaptor Protein ◽  
Therapy Resistance ◽  
Oncogenic Signaling ◽  
Downstream Target ◽  
Anaplastic Lymphoma ◽  
Signaling Axis

Oncogenic anaplastic lymphoma kinase (ALK) is one of the few druggable targets in neuroblastoma, and therapy resistance to ALK-targeting tyrosine kinase inhibitors (TKIs) comprises an inevitable clinical challenge. Therefore, a better understanding of the oncogenic signaling network rewiring driven by ALK is necessary to improve and guide future therapies. Here, we performed quantitative mass spectrometry–based proteomics on neuroblastoma cells treated with one of three clinically relevant ALK TKIs (crizotinib, LDK378, or lorlatinib) or an experimentally used ALK TKI (TAE684) to unravel aberrant ALK signaling pathways. Our integrated proximal proteomics (IPP) strategy included multiple signaling layers, such as the ALK interactome, phosphotyrosine interactome, phosphoproteome, and proteome. We identified the signaling adaptor protein IRS2 (insulin receptor substrate 2) as a major ALK target and an ALK TKI–sensitive signaling node in neuroblastoma cells driven by oncogenic ALK. TKI treatment decreased the recruitment of IRS2 to ALK and reduced the tyrosine phosphorylation of IRS2. Furthermore, siRNA-mediated depletion of ALK or IRS2 decreased the phosphorylation of the survival-promoting kinase Akt and of a downstream target, the transcription factor FoxO3, and reduced the viability of three ALK-driven neuroblastoma cell lines. Collectively, our IPP analysis provides insight into the proximal architecture of oncogenic ALK signaling by revealing IRS2 as an adaptor protein that links ALK to neuroblastoma cell survival through the Akt-FoxO3 signaling axis.

scholarly journals CEP131 Abrogates CHK1 Inhibitor-Induced Replication Defects and Is Associated with Unfavorable Outcome in Neuroblastoma

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Kiyohiro Ando ◽  
Verna Cázares-Ordoñez ◽  
Makoto Makishima ◽  
Atsushi Yokoyama ◽  
Yusuke Suenaga ◽  
...  
Keyword(s):  
Dna Damage ◽  
Therapeutic Strategy ◽  
Neuroblastoma Cell ◽  
Mass Spectrometry Analysis ◽  
Spectrometry Analysis ◽  
Checkpoint Kinase 1 ◽  
Family Protein ◽  
Damage Response ◽  
Chk1 Inhibitor ◽  
Associated Family

Checkpoint kinase 1 (CHK1) plays a key role in genome surveillance and integrity throughout the cell cycle. Selective inhibitors of CHK1 (CHK1i) are undergoing clinical evaluation for various human malignancies, including neuroblastoma. Recently, we reported that CHK1i, PF-477736, induced a p53-mediated DNA damage response. As a result, the cancer cells were able to repair DNA damage and became less sensitive to CHK1i. In this study, we discovered that PF-477736 increased expression of MDM2 oncogene along with CHK1i-induced replication defects in neuroblastoma NB-39-nu cells. A mass spectrometry analysis of protein binding to MDM2 in the presence of CHK1i identified the centrosome-associated family protein 131 (CEP131), which was correlated with unfavorable prognosis of neuroblastoma patients. We revealed that MDM2 was associated with CEP131 protein degradation, whereas overexpression of CEP131 accelerated neuroblastoma cell growth and exhibited resistance to CHK1i-induced replication defects. Thus, these findings may provide a future therapeutic strategy against centrosome-associated oncogenes involving CEP131 as a target in neuroblastoma.

scholarly journals PERIOPERATIVE CHEMOTHERAPY IN LOCALLY ADVANCED GASTRIC CANCER

2013 ◽  
Vol 50 (3) ◽  
pp. 236-242 ◽  
Author(s):  
Thales Paulo BATISTA ◽  
Candice Amorim de Araujo Lima SANTOS ◽  
Gustavo Fernandes Godoy ALMEIDA
Keyword(s):  
Gastric Cancer ◽  
Therapeutic Strategy ◽  
Multimodal Therapy ◽  
Standard Treatment ◽  
Treatment Options ◽  
Locally Advanced ◽  
Special Focus ◽  
Perioperative Chemotherapy ◽  
Locally Advanced Gastric Cancer ◽  
Advanced Stages

Gastric cancer is one of the most common cancers and a main cause of cancer-related death worldwide, since the majority of patients suffering of this malignancy are usually faced with a poor prognosis due to diagnosis at later stages. In order to improve treatment outcomes, the association of surgery with chemo and/or radiotherapy (multimodal therapy) has become the standard treatment for locally advanced stages. However, despite several treatment options currently available for management of these tumors, perioperative chemotherapy has been mainly accepted for the comprehensive therapeutic strategy including an appropriated D2-gastrectomy. This manuscript presents a (nonsystematic) critical review about the use of perioperative chemotherapy, with a special focus on the drugs delivery.

scholarly journals Intercellular transmission of a bacterial cytotoxic prion-like protein in mammalian cells

2019 ◽  
Author(s):  
Aida Revilla-García ◽  
Cristina Fernández ◽  
María Moreno-del Álamo ◽  
Vivian de los Ríos ◽  
Ina M. Vorberg ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Protein Quality ◽  
Horizontal Cell ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Neuroblastoma Cell Line ◽  
Human Neuroblastoma ◽  
Intracellular Traffic ◽  
First Time

AbstractRepA is a bacterial protein that builds intracellular amyloid oligomers acting as inhibitory complexes of plasmid DNA replication. When carrying a mutation enhancing its amyloidogenesis (A31V), the N-terminal domain (WH1) generates cytosolic amyloid particles that are inheritable within a bacterial lineage. Such amyloids trigger in bacteria a lethal cascade reminiscent to mitochondria impairment in human cells affected by neurodegeneration. To fulfil all the features of a prion-like protein, horizontal (intercellular) transmissibility remains to be demonstrated for RepA-WH1. Since this is experimentally intractable in bacteria, here we transiently expressed in a murine neuroblastoma cell line the soluble, barely cytotoxic RepA-WH1(WT) and assayed its response to co-incubation with in vitro assembled RepA-WH1(A31V) amyloid fibres. In parallel, cells releasing RepA-WH1(A31V) aggregates were co-cultured with human neuroblastoma cells expressing RepA-WH1(WT). Both the assembled fibres and the extracellular RepA-WH1(A31V) aggregates induce, in the cytosol of recipient cells, the formation of cytotoxic amyloid particles. Mass spectrometry analyses of the proteomes of both types of injured cells point to alterations in mitochondria, protein quality triage, signalling and intracellular traffic.Summary blurbThe horizontal, cell-to-cell spread of a bacterial prion-like protein is shown for the first time in mammalian cells. Amyloid cross-aggregation of distinct variants, and their associated toxicities, follow the same trend found in bacteria, underlining the universality of prion biology.

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