scholarly journals Clinical validation of genetic variants associated with in vitro chemotherapy-related lymphoblastoid cell toxicity

Oncotarget ◽  
2017 ◽  
Vol 8 (44) ◽  
pp. 78133-78143 ◽  
Author(s):  
Peter A. Fasching ◽  
Lothar Häberle ◽  
Brigitte Rack ◽  
Liang Li ◽  
Alexander Hein ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 750
Author(s):  
Werner E. G. Müller ◽  
Meik Neufurth ◽  
Shunfeng Wang ◽  
Heinz C. Schröder ◽  
Xiaohong Wang

The anti-cancer antitumor antibiotic bleomycin(s) (BLM) induces athyminic sites in DNA after its activation, a process that results in strand splitting. Here, using A549 human lung cells or BEAS-2B cells lunc cells, we show that the cell toxicity of BLM can be suppressed by addition of inorganic polyphosphate (polyP), a physiological polymer that accumulates and is released from platelets. BLM at a concentration of 20 µg ml−1 causes a decrease in cell viability (by ~70%), accompanied by an increased DNA damage and chromatin expansion (by amazingly 6-fold). Importantly, the BLM-caused effects on cell growth and DNA integrity are substantially suppressed by polyP. In parallel, the enlargement of the nuclei/chromatin in BLM-treated cells (diameter, 20–25 µm) is normalized to ~12 µm after co-incubation of the cells with BLM and polyP. A sequential application of the drugs (BLM for 3 days, followed by an exposure to polyP) does not cause this normalization. During co-incubation of BLM with polyP the gene for the BLM hydrolase is upregulated. It is concluded that by upregulating this enzyme polyP prevents the toxic side effects of BLM. These data might also contribute to an application of BLM in COVID-19 patients, since polyP inhibits binding of SARS-CoV-2 to cellular ACE2.


2009 ◽  
Vol 8 (sup2) ◽  
pp. 42-44 ◽  
Author(s):  
Anna Caroli ◽  
Bulgari Bulgari ◽  
Stefania Chessa ◽  
Daniela Cocchi ◽  
Giovanni Tulipano

PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0166891 ◽  
Author(s):  
Kentaro Minagawa ◽  
Muhammad O. Jamil ◽  
Mustafa AL-Obaidi ◽  
Larisa Pereboeva ◽  
Donna Salzman ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Kriti Joshi ◽  
Fergus Cameron ◽  
Swasti Tiwari ◽  
Stuart I. Mannering ◽  
Andrew G. Elefanty ◽  
...  

Induced pluripotent stem cell (iPSC) technology is increasingly being used to create in vitro models of monogenic human disorders. This is possible because, by and large, the phenotypic consequences of such genetic variants are often confined to a specific and known cell type, and the genetic variants themselves can be clearly identified and controlled for using a standardized genetic background. In contrast, complex conditions such as autoimmune Type 1 diabetes (T1D) have a polygenic inheritance and are subject to diverse environmental influences. Moreover, the potential cell types thought to contribute to disease progression are many and varied. Furthermore, as HLA matching is critical for cell-cell interactions in disease pathogenesis, any model that seeks to test the involvement of particular cell types must take this restriction into account. As such, creation of an in vitro model of T1D will require a system that is cognizant of genetic background and enables the interaction of cells representing multiple lineages to be examined in the context of the relevant environmental disease triggers. In addition, as many of the lineages critical to the development of T1D cannot be easily generated from iPSCs, such models will likely require combinations of cell types derived from in vitro and in vivo sources. In this review we imagine what an ideal in vitro model of T1D might look like and discuss how the required elements could be feasibly assembled using existing technologies. We also examine recent advances towards this goal and discuss potential uses of this technology in contributing to our understanding of the mechanisms underlying this autoimmune condition.


2019 ◽  
pp. 31-34
Author(s):  
F. Paprstein ◽  
J. Sedlak ◽  
J. Polak ◽  
S. Kumari

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Jéssica Rebouças-Silva ◽  
Fabiana S. Celes ◽  
Jonilson Berlink Lima ◽  
Hernane S. Barud ◽  
Camila I. de Oliveira ◽  
...  

Treatments based on antimonials to cutaneous leishmaniasis (CL) entail a range of toxic side effects. Propolis, a natural compound widely used in traditional medical applications, exhibits a range of biological effects, including activity against infectious agents. The aim of this study was to test the potential leishmanicidal effects of different propolis extracts against Leishmania (Viannia) braziliensis promastigotes and intracellular amastigotes in vitro. Stationary-phase L. (V) braziliensis promastigotes were incubated with medium alone or treated with dry, alcoholic, or glycolic propolis extract (10, 50, or 100 μg/mL) for 96 h. Our data showed that all extracts exhibited a dose-dependent effect on the viability of L. (V) braziliensis promastigotes, while controlling the parasite burden inside infected macrophages. Dry propolis extract significantly modified the inflammatory profile of murine macrophages by downmodulating TGF-β and IL-10 production, while upmodulating TNF-α. All three types of propolis extract were found to reduce nitric oxide and superoxide levels in activated L. braziliensis-infected macrophages. Altogether, our results showed that propolis extracts exhibited a leishmanicidal effect against both stages of L. (V) braziliensis. The low cell toxicity and efficient microbicidal effect of alcoholic or glycolic propolis extracts make them candidates to an additive treatment for cutaneous leishmaniasis.


2014 ◽  
Vol 203 (5) ◽  
pp. 341-355 ◽  
Author(s):  
Joanna Boros-Majewska ◽  
Natalia Salewska ◽  
Edward Borowski ◽  
Sławomir Milewski ◽  
Sladjana Malic ◽  
...  

2017 ◽  
pp. 425-430
Author(s):  
I.-C. Guţă ◽  
E.-C. Buciumeanu ◽  
C.M. Topală ◽  
L.D. Tătaru

2009 ◽  
Vol 11 (4) ◽  
pp. 56 ◽  
Author(s):  
Tomoaki Kurosaki ◽  
Takashi Kitahara ◽  
Mugen Teshima ◽  
Koyo Nishida ◽  
Junzo Nakamura ◽  
...  

Purpose: In gene delivery, a fusogenic lipid such as dioleyl phosphatidylethanolamine (DOPE) which is a component of cationic liposomal vector is important factor for effective transfection efficiency. We investigated the effect of penetration enhancers as alternative helper-lipids to DOPE. Methods: Transdermal penetraion enhancers such as N-lauroylsarcosine (LS), (R)-(+)-limonene (LM), vitamin E (VE), and phosphatidyl choline from eggs (EggPC) were used in this experiments as helper-lipids with N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethlylammonium chloride (DOTMA) and cholesterol (CHOL). We examined in vitro transfection efficiency, cytotoxicity, hematotoxicity, and in vivo transfection efficiency of plasmid DNA/cationic liposomes complexes. Results: In transfection experiments in vitro, the cationic lipoplexes containing LS had highest transfection efficiency among the other lipoplexes independently of FBS. Furthermore, the lipoplexes containing LS had lowest cell toxicity among the other lipoplexes in the presence of FBS. As the results of erythrocytes interaction experiment, DOTMA/LS/CHOL, DOTMA/VE/CHOL, and DOTMA/EggPC/CHOL lipoplexes showed extremely lower hematotoxicity. On the basis of these results, the in vivo transfection efficiencies of the lipoplexes were examined. The lipoplexes containing LS had the highest transfection activity among the other lipoplexes. Conclusion: In conclusion, several transdermal penetration enhancers are available for alternative helper-lipids to DOPE in cationic liposomal vectors. Among them, DOTMA/LS/CHOL lipoplexes showed superior characteristics in in vitro transfection efficiency, cell toxicity, hematotoxicity, and in vivo transfection efficiency.


2013 ◽  
Vol 40 (No. 4.) ◽  
pp. 186-190 ◽  
Author(s):  
F. Parštein ◽  
J. Sedlák ◽  
L. Svobodová ◽  
J. Polák ◽  
S. Gadiou

The effect of the chemotherapy with ribavirin on the elimination of the pome fruit viruses from in vitro grown plants of infected apple cv. Fragnance has been investigated. The results of ELISA and RT-PCR testing proved the presence of mixed infection of Apple stem pitting virus (ASPV), Apple chlorotic leaf spot virus (ACLSV) and Apple stem grooving virus (ASGV) in the initial field-grown tree of this apple cultivar. Obtained actively growing in vitro shoots with well-developed leaves and shoot tips were subsequently used for chemotherapy with ribavirin. Attempts to fully eliminate viruses by ribavirin in lower concentration 20 mg/l were not successful. However in vitro plants of one mericlone (FR1R20) sanitated from ASPV and ASGV, which were infected with ACLSV only after the first chemotherapy cycle, were subjected to repeated treatment on medium with higher ribavirin concentration 100 mg/l. The success of chemotherapy with ribavirin at 100 mg/l was 76% for ACLSV elimination after the second round. In the course of both chemotherapy cycles (20 mg/l and 100 mg/l), in vitro plants did not display symptoms of phytotoxicity.


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