scholarly journals IL-4 Counteracts the Cytotoxic Effects of Peripheral Blood Mononuclear Cells on Hormone-sensitive Prostate Cancer Cells

In Vivo ◽  
2021 ◽  
Vol 35 (4) ◽  
pp. 1973-1977
Author(s):  
HOLGER H.H. ERB ◽  
ZORAN CULIG ◽  
MATTHIAS B. STOPE
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Prostate Cancer Cells ◽  
Peripheral Blood Mononuclear ◽  
Cytotoxic Effects ◽  
Blood Mononuclear Cells ◽  
Hormone Sensitive

scholarly journals α-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [223Ra]RaCl2-treated prostate cancer patients

2021 ◽  
Author(s):  
S. Schumann ◽  
U. Eberlein ◽  
C. Lapa ◽  
J. Müller ◽  
S. Serfling ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
Cancer Patients ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Absorbed Dose ◽  
Peripheral Blood Mononuclear ◽  
Absorbed Doses ◽  
Blood Mononuclear Cells

Abstract Purpose One therapy option for prostate cancer patients with bone metastases is the use of [223Ra]RaCl2. The α-emitter 223Ra creates DNA damage tracks along α-particle trajectories (α-tracks) in exposed cells that can be revealed by immunofluorescent staining of γ-H2AX+53BP1 DNA double-strand break markers. We investigated the time- and absorbed dose-dependency of the number of α-tracks in peripheral blood mononuclear cells (PBMCs) of patients undergoing their first therapy with [223Ra]RaCl2. Methods Multiple blood samples from nine prostate cancer patients were collected before and after administration of [223Ra]RaCl2, up to 4 weeks after treatment. γ-H2AX- and 53BP1-positive α-tracks were microscopically quantified in isolated and immuno-stained PBMCs. Results The absorbed doses to the blood were less than 6 mGy up to 4 h after administration and maximally 16 mGy in total. Up to 4 h after administration, the α-track frequency was significantly increased relative to baseline and correlated with the absorbed dose to the blood in the dose range < 3 mGy. In most of the late samples (24 h – 4 weeks after administration), the α-track frequency remained elevated. Conclusion The γ-H2AX+53BP1 assay is a potent method for detection of α-particle-induced DNA damages during treatment with or after accidental incorporation of radionuclides even at low absorbed doses. It may serve as a biomarker discriminating α- from β-emitters based on damage geometry.

scholarly journals In Vitro Cytotoxic Effect of 2-(Morpholin-4-Yl)-4,5-Bis(2’’,2’’,2’’-Trinitroethoxy)-1,3,5-Triazine on Human Fibroblasts, Peripheral Blood Mononuclear Cells and Breast Cancer Cells

2021 ◽  
Author(s):  
Larisa Limareva ◽  
Pavel Iliasov ◽  
Alexander Gidaspov ◽  
Vladimir Zalomlenkov ◽  
Aleksey Sustretov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Breast Cancer Cells ◽  
Mononuclear Cells ◽  
Human Fibroblasts ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

2-(Morpholin-4-yl)-4,5-bis(2&rsquo;&rsquo;,2&rsquo;&rsquo;,2&rsquo;&rsquo;-trinitroethoxy)-1,3,5-triazine having QSAR-predicted anti-tumor activity was tested for the cytotoxicity using MTT and LDH cell viability tests. The experiments were conducted using human fibroblasts, peripheral blood mononuclear cells and breast cancer cells and allowed to identify effective cytotoxic concentration ant therapeutic range of this compound. The data obtained suggest the feasibility of the further studies of the test compound as a potential anti-cancer agent.

scholarly journals Intracellular Signaling in Key Pathways Is Induced by Treatment with Ultrasound and Microbubbles in a Leukemia Cell Line, but Not in Healthy Peripheral Blood Mononuclear Cells

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 319 ◽  
Author(s):  
Ragnhild Haugse ◽  
Anika Langer ◽  
Stein-Erik Gullaksen ◽  
Silje Sundøy ◽  
Bjørn Gjertsen ◽  
...  
Keyword(s):  
Protein Phosphorylation ◽  
Cancer Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Therapeutic Efficacy ◽  
Mononuclear Cells ◽  
Leukemia Cell Line ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Ultrasound Microbubbles

Treatment with ultrasound and microbubbles (sonoporation) to enhance therapeutic efficacy in cancer therapy is rapidly expanding, but there is still very little consensus as to why it works. Despite the original assumption that pore formation in the cell membrane is responsible for increased uptake of drugs, the molecular mechanisms behind this phenomenon are largely unknown. We treated cancer cells (MOLM-13) and healthy peripheral blood mononuclear cells (PBMCs) with ultrasound at three acoustic intensities (74, 501, 2079 mW/cm2) ± microbubbles. We subsequently monitored the intracellular response of a number of key signaling pathways using flow cytometry or western blotting 5 min, 30 min and 2 h post-treatment. This was complemented by studies on uptake of a cell impermeable dye (calcein) and investigations of cell viability (cell count, Hoechst staining and colony forming assay). Ultrasound + microbubbles resulted in both early changes (p38 (Arcsinh ratio at high ultrasound + microbubbles: +0.5), ERK1/2 (+0.7), CREB (+1.3), STAT3 (+0.7) and AKT (+0.5)) and late changes (ribosomal protein S6 (Arcsinh ratio at low ultrasound: +0.6) and eIF2α in protein phosphorylation). Observed changes in protein phosphorylation corresponded to changes in sonoporation efficiency and in viability, predominantly in cancer cells. Sonoporation induced protein phosphorylation in healthy cells was pronounced (p38 (+0.03), ERK1/2 (−0.03), CREB (+0.0), STAT3 (−0.1) and AKT (+0.04) and S6 (+0.2)). This supports the hypothesis that sonoporation may enhance therapeutic efficacy of cancer treatment, without causing damage to healthy cells.

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