scholarly journals Divergent leukaemia subclones as cellular models for testing vulnerabilities associated with gains in chromosomes 7, 8 or 18

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michael Maher ◽  
Jeannine Diesch ◽  
Marguerite-Marie Le Pannérer ◽  
Marta Cabezón ◽  
Mar Mallo ◽  
...  
Keyword(s):  
Cell Lines ◽  
Synthetic Lethality ◽  
Partial Trisomy ◽  
In Vitro Models ◽  
Chromosome 8 ◽  
Chromosome 7 ◽  
Specific Response ◽  
Cellular Models ◽  
Mutational Pattern

AbstractHaematopoietic malignancies are frequently characterized by karyotypic abnormalities. The development of targeted drugs has been pioneered with compounds against gene products of fusion genes caused by chromosomal translocations. While polysomies are equally frequent as translocations, for many of them we are lacking therapeutic approaches aimed at synthetic lethality. Here, we report two new cell lines, named MBU-7 and MBU-8, that differ in complete trisomy of chromosome18, a partial trisomy of chromosome 7 and a tetrasomy of the p-arm of chromosome 8, but otherwise share the same mutational pattern and complex karyotype. Both cell lines are divergent clones of U-937 cells and have the morphology and immunoprofile of monocytic cells. The distinct karyotypic differences between MBU-7 and MBU-8 are associated with a difference in the specific response to nucleoside analogues. Taken together, we propose the MBU-7 and MBU-8 cell lines described here as suitable in vitro models for screening and testing vulnerabilities that are associated with the disease-relevant polysomies of chromosome 7, 8 and 18.

Malignant hematopoietic cell lines: In vitro models for the study of primary mediastinal B-cell lymphomas

2015 ◽  
Vol 39 (1) ◽  
pp. 18-29 ◽  
Author(s):  
Hans G. Drexler ◽  
Stefan Ehrentraut ◽  
Stefan Nagel ◽  
Sonja Eberth ◽  
Roderick A.F. MacLeod
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
In Vitro Models ◽  
Hematopoietic Cell ◽  
B Cell Lymphomas ◽  
Hematopoietic Cell Lines

Hepatoma Cell Cultures as In Vitro Models for the Hepatotoxicity of Xenobiotics

1988 ◽  
Vol 16 (1) ◽  
pp. 32-37
Author(s):  
Margherita Ferro ◽  
Anna Maria Bassi ◽  
Giorgio Nanni
Keyword(s):  
Cell Lines ◽  
Cell Cultures ◽  
Membrane Lipids ◽  
Hepatoma Cell ◽  
Positive Control ◽  
In Vitro Models ◽  
Low Concentrations ◽  
Formation Efficiency ◽  
Dose Dependent

Two hepatoma cell cultures were examined as in vitro models to be used in genotoxicity and cytotoxicity tests without the addition of bioactivating enzymes. The MH1C1, and HTC hepatoma lines were used in this study to establish their sensitivity to a number of xenobiotics, namely, cyclophosphamide (CP), the classical positive control in bioactivation tests; benzaldehyde (BA), a short-chain aldehyde; and 4-hydroxynonenal (HNE), a major toxic end-product of the peroxidative degradation of cell membrane lipids. As a first approach, we compared the following cytotoxicity tests: release of lactate dehydrogenase (LDH), and colony formation efficiency (CF). Colony-forming cells were exposed to the drugs according to different procedures, before or after the anchorage phase. The leakage of LDH into the medium following exposure of both cell lines to HNE, CP and BA for up to 24 hours was found not to be a good index of cytotoxicity. A better indicator of cytotoxicity was CF, as evaluated by exposure of the cells 24 hours after seeding. The effects were detectable at very low concentrations, corresponding to 10, 90 and 100μM for HNE, CP and BA, respectively. The impairment of CF efficiency was dose-dependent and time-dependent, and several differences between the two cell lines were observed.

scholarly journals The Current Challenges for Drug Discovery in CNS Remyelination

2021 ◽  
Vol 22 (6) ◽  
pp. 2891
Author(s):  
Sonia Balestri ◽  
Alice Del Giovane ◽  
Carola Sposato ◽  
Marta Ferrarelli ◽  
Antonella Ragnini-Wilson
Keyword(s):  
Drug Screening ◽  
Myelin Sheath ◽  
Time Window ◽  
In Vitro Models ◽  
Adult Brain ◽  
Pharmacological Intervention ◽  
Cellular Models ◽  
New Findings ◽  
Myelin Injury

The myelin sheath wraps around axons, allowing saltatory currents to be transmitted along neurons. Several genetic, viral, or environmental factors can damage the central nervous system (CNS) myelin sheath during life. Unless the myelin sheath is repaired, these insults will lead to neurodegeneration. Remyelination occurs spontaneously upon myelin injury in healthy individuals but can fail in several demyelination pathologies or as a consequence of aging. Thus, pharmacological intervention that promotes CNS remyelination could have a major impact on patient’s lives by delaying or even preventing neurodegeneration. Drugs promoting CNS remyelination in animal models have been identified recently, mostly as a result of repurposing phenotypical screening campaigns that used novel oligodendrocyte cellular models. Although none of these have as yet arrived in the clinic, promising candidates are on the way. Many questions remain. Among the most relevant is the question if there is a time window when remyelination drugs should be administrated and why adult remyelination fails in many neurodegenerative pathologies. Moreover, a significant challenge in the field is how to reconstitute the oligodendrocyte/axon interaction environment representative of healthy as well as disease microenvironments in drug screening campaigns, so that drugs can be screened in the most appropriate disease-relevant conditions. Here we will provide an overview of how the field of in vitro models developed over recent years and recent biological findings about how oligodendrocytes mature after reactivation of their staminal niche. These data have posed novel questions and opened new views about how the adult brain is repaired after myelin injury and we will discuss how these new findings might change future drug screening campaigns for CNS regenerative drugs.

scholarly journals Effects of Platelet-Rich Plasma on Cellular Populations of the Central Nervous System: The Influence of Donor Age

2021 ◽  
Vol 22 (4) ◽  
pp. 1725
Author(s):  
Diego Delgado ◽  
Ane Miren Bilbao ◽  
Maider Beitia ◽  
Ane Garate ◽  
Pello Sánchez ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cellular Response ◽  
Platelet Rich Plasma ◽  
Biological Response ◽  
In Vitro Models ◽  
Molecular Composition ◽  
Cellular Models ◽  
The Central Nervous System

Platelet-rich plasma (PRP) is a biologic therapy that promotes healing responses across multiple medical fields, including the central nervous system (CNS). The efficacy of this therapy depends on several factors such as the donor’s health status and age. This work aims to prove the effect of PRP on cellular models of the CNS, considering the differences between PRP from young and elderly donors. Two different PRP pools were prepared from donors 65–85 and 20–25 years old. The cellular and molecular composition of both PRPs were analyzed. Subsequently, the cellular response was evaluated in CNS in vitro models, studying proliferation, neurogenesis, synaptogenesis, and inflammation. While no differences in the cellular composition of PRPs were found, the molecular composition of the Young PRP showed lower levels of inflammatory molecules such as CCL-11, as well as the presence of other factors not found in Aged PRP (GDF-11). Although both PRPs had effects in terms of reducing neural progenitor cell apoptosis, stabilizing neuronal synapses, and decreasing inflammation in the microglia, the effect of the Young PRP was more pronounced. In conclusion, the molecular composition of the PRP, conditioned by the age of the donors, affects the magnitude of the biological response.

Leukemia cell lines: In vitro models for the study of acute promyelocytic leukemia

1995 ◽  
Vol 19 (10) ◽  
pp. 681-691 ◽  
Author(s):  
H.G. Drexler ◽  
H. Quentmeier ◽  
R.A.F. MacLeod ◽  
C.C. Uphoff ◽  
Z.-B. Hu
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Cell Lines ◽  
Leukemia Cell ◽  
In Vitro Models ◽  
Promyelocytic Leukemia ◽  
Leukemia Cell Lines

scholarly journals Cytocidal Antitumor Effects against Human Ovarian Cancer Cells Induced by B-Lactam Steroid Alkylators with Targeted Activity against Poly (ADP-Ribose) Polymerase (PARP) Enzymes in a Cell-Free Assay

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1028
Author(s):  
Nikolaos Nikoleousakos ◽  
Panagiotis Dalezis ◽  
Aikaterini Polonifi ◽  
Elena G. Geromichalou ◽  
Sofia Sagredou ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Cell Lines ◽  
Synthetic Lethality ◽  
Parp Inhibitor ◽  
Positive Control ◽  
Ovarian Cancer Cells ◽  
Antitumor Effects

We evaluated three newly synthesized B-lactam hybrid homo-aza-steroidal alkylators (ASA-A, ASA-B and ASA-C) for their PARP1/2 inhibition activity and their DNA damaging effect against human ovarian carcinoma cells. These agents are conjugated with an alkylating component (POPA), which also served as a reference molecule (positive control), and were tested against four human ovarian cell lines in vitro (UWB1.289 + BRCA1, UWB1.289, SKOV-3 and OVCAR-3). The studied compounds were thereafter compared to 3-AB, a known PARP inhibitor, as well as to Olaparib, a standard third-generation PARP inhibitor, on a PARP assay investigating their inhibitory potential. Finally, a PARP1 and PARP2 mRNA expression analysis by qRT-PCR was produced in order to measure the absolute and the relative gene expression (in mRNA transcripts) between treated and untreated cells. All the investigated hybrid steroid alkylators and POPA decreased in vitro cell growth differentially, according to the sensitivity and different gene characteristics of each cell line, while ASA-A and ASA-B presented the most significant anticancer activity. Both these compounds induced PARP1/2 enzyme inhibition, DNA damage (alkylation) and upregulation of PARP mRNA expression, for all tested cell lines. However, ASA-C underperformed on average in the above tasks, while the compound ASA-B induced synthetic lethality effects on the ovarian cancer cells. Nevertheless, the overall outcome, leading to a drug-like potential, provides strong evidence toward further evaluation.

scholarly journals Comparing various epithelial cell lines as in vitro models for Francisella tularensis non‐phagocytic infections

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Karen Y Lo ◽  
Michael D Chua ◽  
Salima Abdulla ◽  
HT Law ◽  
Julian A Guttman
Keyword(s):  
Epithelial Cell ◽  
Cell Lines ◽  
Francisella Tularensis ◽  
In Vitro Models ◽  
Epithelial Cell Lines

Chromosome 7 suppresses indefinite division of nontumorigenic immortalized human fibroblast cell lines KMST-6 and SUSM-1

1993 ◽  
Vol 13 (10) ◽  
pp. 6036-6043
Author(s):  
T Ogata ◽  
D Ayusawa ◽  
M Namba ◽  
E Takahashi ◽  
M Oshimura ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cell ◽  
Human Fibroblasts ◽  
Fibroblast Cell ◽  
Chromosome 7 ◽  
In Vitro Mutagenesis ◽  
Human Cell Lines ◽  
First Case ◽  
Normal Human

Using nontumorigenic immortalized human cell lines KMST-6 (KMST) and SUSM-1 (SUSM), we attempted to identify the chromosome that carries a putative senescence-related gene(s). These cell lines are the only ones that have been established independently from normal human diploid fibroblasts following in vitro mutagenesis. We first examined restriction fragment length polymorphisms on each chromosome of these immortalized cell lines and their parental cell lines and found specific chromosomal alterations common to these cell lines (a loss of heterozygosity in KMST and a deletion in SUSM) on the long arm of chromosome 7. In addition to these, we also found that introduction of chromosome 7 into these cell lines by means of microcell fusion resulted in the cessation of cell division, giving rise to cells resembling cells in senescence. Introduction of other chromosomes, such as chromosomes 1 and 11, on which losses of heterozygosity were also detected in one of the cell lines (KMST), to either KMST or SUSM cells or of chromosome 7 to several tumor-derived cell lines had no effect on their division potential. These results strongly suggest that a gene(s) affecting limited-division potential or senescence of normal human fibroblasts is located on chromosome 7, probably at the long arm of the chromosome, representing the first case in which a specific chromosome reverses the immortal phenotype of otherwise normal human cell lines.

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