scholarly journals Irinotecan (CPT-11) Canonical Anti-Cancer Drug Can also Modulate Antiviral and Pro-Inflammatory Responses of Primary Human Synovial Fibroblasts

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1431
Author(s):  
Anthony Dobi ◽  
Philippe Gasque ◽  
Pascale Guiraud ◽  
Jimmy Selambarom
Keyword(s):  
Stromal Cells ◽  
Inflammatory Responses ◽  
Synovial Fibroblasts ◽  
Cancer Drug ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Antiviral Therapies ◽  
Polycytidylic Acid ◽  
Anti Cancer ◽  
Polyinosinic Polycytidylic Acid

Alphaviruses are a group of arboviruses that generate chronic inflammatory rheumatisms in humans. Currently, no approved vaccines or antiviral therapies are available to prevent or treat alphavirus-induced diseases. The aim of this study was to evaluate the repositioning of the anti-cancer molecule irinotecan as a potential modulator of the antiviral and inflammatory responses of primary human synovial fibroblasts (HSF), the main stromal cells of the joint synovium. HSF were exposed to O’nyong-nyong virus (ONNV) and polyinosinic-polycytidylic acid (PIC) to mimic, respectively, acute and chronic infectious settings. The cytokine IL-1β was used as a major pro-inflammatory cytokine to stimulate HSF. Quantitative RT-PCR analysis revealed that irinotecan at 15 µM was able to amplify the antiviral response (i.e., interferon-stimulated gene expression) of HSF exposed to PIC and reduce the expression of pro-inflammatory genes (CXCL8, IL-6 and COX-2) upon IL-1β treatment. These results were associated with the regulation of the expression of several genes, including those encoding for STAT1, STAT2, p53 and NF-κB. Irinotecan did not modulate these responses in both untreated cells and cells stimulated with ONNV. This suggests that this drug could be therapeutically useful for the treatment of chronic and severe (rather than acute) arthritis due to viruses.

In Vivo Modulation of T Cell and Monocyte Function Following Infusion of Mesenchymal Stromal Cells (MSC)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4739-4739
Author(s):  
Cristina Castilla-LLorente ◽  
Mineo Iwata ◽  
Marco Mielcarek ◽  
V. Kraig Abrams ◽  
Billanna Hwang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Lymph Nodes ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Blood Mononuclear Cells ◽  
Post Infusion

Abstract Mesenchymal stromal cells (MSCs) expanded ex vivo from aspirated marrow, have been used clinically with variable success to facilitate repair of infarcted hearts, treat graft versus host disease, and facilitate marrow reconstitution after radiation damage. While it is now generally acknowledged that these benefits are not the result of engraftment and differentiation of MSC into the target tissues, the mechanism by which these beneficial effects are achieved is not clear. We hypothesize that MSCs mediate their effect by activating an endogenous cell population which in turn modulates the immune response and/or homes to damaged tissue and participates in repair. To begin to test this hypothesis immortalized and cloned populations of canine MSC were generated to provide a consistent product for in vivo testing. One line, designated DS-1, has been evaluated in vivo by infusion into two normal dogs. Blood samples were taken pre infusion, immediately following infusion and at 1, 6, 24, 48, 72, 96 hours, and 7, 14, 21, and 28 days post infusion. Following infusion there was no consistent change in the number of WBC, however by day 3 there was a marked decrease in the % of CD3+ cells expressing FOXP3 and TGFβ in the blood, which did not recover to pre-infusion levels during the period of observation. At autopsy there was an increased number of these cells in the lymph nodes and spleen, whereas there was an overall decrease in the number of TH1 cells in these tissues. Quantitative RT- PCR analysis of cDNA prepared from blood mononuclear cells indicated an upregulation in the expression of CD133, Tie-2, and MARCO between 1–24 hours post infusion, and an increase in LOX1/OLR1 between 2–4 days. However the % of monocytes and the expression levels of CD14, CD68, CD45, and CD105/Endoglin were constant at all time points. Samples taken at 6 hours, 4 and 7 days post infusion were also analyzed for the presence of DS-1 cells by PCR and in vitro out growth assays. Results indicated that the DS-1cells were detectable up to 6 hours post infusion, but not thereafter. Adherent cells grown from blood mononuclear cells at days 4 and 7, displayed macrophage and endothelial cell morphologies. RT-PCR analysis of these cultures detected expression of macrophage associated markers CD14+/CD68+/MARCO+/LOX1+, as well as endothelial cell associated markers CD34+/CD144/VECAD+. These data indicate that a single infusion of DS-1 cells results in activation of circulating monocytes and a shift of regulatory T cells from the periphery to lymph nodes and spleen which persists for at least 28 days. We speculate that these changes may contribute to the immunomodulatory effects reported for some preparations of MSC.

Killing cancer cells using nanotechnology: novel poly(I:C) loaded liposome–silica hybrid nanoparticles

2015 ◽  
Vol 3 (37) ◽  
pp. 7408-7416 ◽  
Author(s):  
Valentina Colapicchioni ◽  
Sara Palchetti ◽  
Daniela Pozzi ◽  
Elettra Sara Marini ◽  
Anna Riccioli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Hybrid Nanoparticles ◽  
Poly I:C ◽  
Core Shell ◽  
Polycytidylic Acid ◽  
Anti Cancer ◽  
Polyinosinic Polycytidylic Acid ◽  
Silica Hybrid

Synthesized core–shell liposome–silica hybrid nanoparticles (LSH NPs), when loaded with the anti-cancer polyinosinic–polycytidylic acid (poly(I:C)), exhibit high anti-tumoral activity in prostate and breast cancer cells.

scholarly journals Up-regulation of Per1 expression by estradiol and progesterone in the rat uterus

2007 ◽  
Vol 194 (3) ◽  
pp. 511-519 ◽  
Author(s):  
Pei-Jian He ◽  
Masami Hirata ◽  
Nobuhiko Yamauchi ◽  
Masa-aki Hattori
Keyword(s):  
Stromal Cells ◽  
Clock Genes ◽  
Staining Intensity ◽  
Reproductive Organ ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Rat Uterus ◽  
Ovarian Steroids ◽  
Direct Regulation

It has been established that estrogen can alter circadian rhythms in behavior and endocrine physiology in rodents. The uterus is a reproductive organ that is critically dependent on regulation by ovarian steroids. Here, we examined the expression of Per1 in different compartments of the uterus, and explored whether the ovarian steroids could regulate Per1 expression employing ovariectomized rat uterus. RT-PCR analysis showed that Per1 was cyclically expressed in the uterus. As revealed by in situ hybridization, the staining intensity of Per1 mRNA was stronger at ZT 8 than at ZT 0 in the uterine luminal epithelium (LE), stroma (S), and myometrium (M) compartments, but was not changed in the glandular epithelium (GE). Both in situ hybridization and immunofluorescence analyses revealed that estradiol (E2) administration induced high expression of Per1 in the LE, GE, and M, and less expression in the S compartment. Progesterone (P4) treatment resulted in an obvious enhancement of Per1 expression in the LE, GE, and S, but unchanged in the M compartment. Furthermore, the E2- and P4-activated Per1 expression was significantly repressed by their respective antagonists, ICI182 780 and RU486. These findings were further supported by RT-PCR analysis of Per1 expression in cultured uterine stromal cells. Collectively, the present data indicate that E2 and P4 might be involved in modification of circadian rhythm via direct regulation of the expression of clock genes.

scholarly journals Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems

2016 ◽  
Vol 11 (1) ◽  
pp. 98-111 ◽  
Author(s):  
Darinka Gjorgieva Ackova ◽  
Tatjana Kanjevac ◽  
Lia Rimondini ◽  
Darko Bosnakovski
Keyword(s):  
Drug Delivery ◽  
Stromal Cells ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Cancer Drug ◽  
Anti Cancer ◽  
Cancer Drug Delivery

Real-time quantitative RT-PCR analysis of human bone marrow stromal cells during osteogenic differentiation in vitro

2002 ◽  
Vol 85 (4) ◽  
pp. 737-746 ◽  
Author(s):  
Oliver Frank ◽  
Manuel Heim ◽  
Marcel Jakob ◽  
Andrea Barbero ◽  
Dirk Schäfer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Osteogenic Differentiation ◽  
Real Time ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Human Bone ◽  
Pcr Analysis ◽  
Rt Pcr

Anti-Tumour Effects of Exosomes in Combination with Cyclophosphamide and Polyinosinic–Polycytidylic Acid

2008 ◽  
Vol 36 (6) ◽  
pp. 1342-1353 ◽  
Author(s):  
F Guo ◽  
CK Chang ◽  
HH Fan ◽  
XX Nie ◽  
YN Ren ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Poly I:C ◽  
Spleen Cells ◽  
Polycytidylic Acid ◽  
Anti Tumour Activity ◽  
Anti Cancer ◽  
Tumour Activity ◽  
Dc Maturation ◽  
Polyinosinic Polycytidylic Acid

We examined the anti-tumour activity of exosomes derived from dendritic cells (DCs) in combination with cyclophosphamide (CTX) and polyinosinic–polycytidylic acid sodium salt (poly I:C). DCs were pulsed with L1210 lymphocytic leukaemia cell antigen and lipopolysaccharide. The exosomes that the DCs secreted were purified. In vitro, the anti-tumour activity of exosomes was assessed by measuring their ability to induce spleen cell proliferation and the extent to which they induced spleen cells to kill L1210 cells. Poly I:C was able to induce DC maturation. DC-derived exosomes stimulated spleen cell proliferation and enhanced the cytotoxic effects of spleen cells in vitro. DC-derived exosomes, in combination with CTX and poly I:C, suppressed L1210 tumour growth in vivo and gave the greatest prolongation of survival time in tumour-bearing DBA2 mice. These findings suggest that this combination of a tumour vaccine, a conventional anti-cancer agent and a promoter of DC maturation might be a useful anti-cancer therapy.

Cell Specific Targeting of Multifunctional γ-Fe2O3 Nanoparticles Through Surface Binding of dsDNA

2007 ◽  
Vol 1032 ◽  
Author(s):  
Wolfgang Tremel ◽  
Mohammed Ibrahim Shukoor ◽  
Filipe Natalio ◽  
Muhammad Nawaz Tahir ◽  
Werner E. G. Müller ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Line ◽  
Maghemite Nanoparticles ◽  
Fe2o3 Nanoparticles ◽  
Rt Pcr ◽  
Surface Binding ◽  
Specific Targeting ◽  
Polycytidylic Acid ◽  
Polyinosinic Polycytidylic Acid

AbstractThe immobilization of polyinosinic-polycytidylic acid [poly(IC)] on ã-Fe2O3 maghemite nanoparticles via the phosphor-amidate route using a multifunctional polymer is reported. The dsRNA coupled nanoparticles were used to visualize the Toll-like (TLR3) receptors at the cell surface. The presence of TLR3 was demonstrated independently in the Caki-1 cell line by RT-PCR and immunostaining techniques

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