scholarly journals Influence of Flavonoids on the Cytotoxic Activity of Mononuclear Blood Cells in Model Tests

2019 ◽  
Vol 7 (12) ◽  
pp. 1900-1904 ◽  
Author(s):  
Liudmila Ivanovna Babaskina ◽  
Tatiana Mikhailovna Litvinova ◽  
Dmitrii Vladimirovich Babaskin ◽  
Mikhail Valentinovich Kiselevsky ◽  
Olga Vladimirovna Savinova ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Blood Cells ◽  
Cytotoxic Effect ◽  
Mononuclear Cells ◽  
Tumour Cells ◽  
Immunomodulatory Activity ◽  
Target Cells ◽  
Killer Activity ◽  
Mononuclear Blood Cells

BACKGROUND: The spread of phytocomplex application and justification of its selective effects on tumour cells (mainly due to the presence of flavonoids) require research of its cytotoxic and immunomodulatory activity. AIM: The goal was to study the direct cytotoxic effect of the phytocomplex and its modulating effect on the cytotoxic activity of the donor's mononuclear blood cells in in vitro experiments. METHODS: The phytocomplex was a dry extract from marsh cinquefoil, creeping alfalfa and common hop; its main active ingredients were flavonoids. Transplantable monolayer cultures of lung adenocarcinoma, colorectal cancer, erythroblastic leukaemia, and fibroblasts were used as target cells. The cytotoxic activity was assessed using a cytotoxic test based on the selective ability to live cells to reduce MTT (3-[4, 5-dimethyltriazol-2-yl]-2, 5 diphenyltetrazolium bromide) to formazan in mitochondria. Quantitative determination of formazan was performed using spectrophotometry. RESULTS: A direct cytotoxic effect of the phytocomplex in concentrations of at least 2.5 mg/ml on tumour cells has been established. Its modulating effect on the cytotoxic activity of mononuclear blood cells at a concentration of 0.05 mg/ml was shown. The phytocomplex in doses of 0.25 and 0.5 mg/ml increased the killer activity of the mononuclear cells in a diseased person's blood, but did not affect these blood cells in a healthy donor. Incubation of lymphocytes with a phytocomplex for 24 hours increased the cytotoxic activity of mononuclear cells by 20-25%. CONCLUSION: The direct cytotoxic effect of the phytocomplex and its modulating effect on the cytotoxic activity of mononuclear blood cells in model experiments in vitro have been established.

Interleukin 21 Enhances the Expansion and Anti-Tumor Cytotoxic Activity of Cytokine-Induced Killer Cells Derived from Both Peripheral Blood and Cord Blood In Vitro.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4887-4887
Author(s):  
Mingfeng Zhao ◽  
Qi Deng ◽  
Yuming Li ◽  
Xuemei Lin ◽  
Li Geng ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Myeloid Leukemia ◽  
Mononuclear Cells ◽  
Culture Supernatant ◽  
K562 Cells ◽  
Target Cells ◽  
Cik Cells ◽  
Interleukin 21 ◽  
Anti Tumor Activity

Abstract Interleukin 21(IL-21) is a new member of interleukin 2 cytokine families which was discovered in 2000. IL-21 is produced by activated CD4 positive cells, and is known to influence T, B, NK cells and DC, and has potent anti-tumor effects. For example, IL-21 can improve the proliferation of B lymphocytes, enhance the production of IgG1; improve the proliferation and enhance the anti-tumor activity of both NK and T cells. The cytokine-induced killer (CIK) cells, which are characterized with the phenotype of CD3+CD56+, are the effective cells on adoptive cellular immunotherapy against tumors. We hypothesize that IL-21 could also affect the proliferation and function of CIK cells, thus play a certain role in the anti-tumor immunotherapy by CIK cells. The peripheral blood mononuclear cells (PBMC) and cord blood mononuclear cells (CBMC) from healthy donors were stimulated with anti-CD3 (OKT3) monoclonal antibody and IFNgamma and then expanded with IL-2 and with/without IL-21(200ng/ml). CD3+CD56+ CIK cells were counted by flow cytometry. Net lactate dehydrogenase release from target cells incubated with CIK cells was used as an index of CIK cells cytotoxicity against chronic myeloid leukemia cell line K562 and a variety of tumor target cells from patients. The concentration of the IFNgamma in the culture supernatant was measured by enzyme-linked-immunoassay, the quantity of IFNgamma RNA was measured by RT-PCR assay, and the cytotoxic activity against K562 cells by the culture supernatant was also detected. Cultured with IL-21, at day 14, the quantity of CIK cells was increased from a median of 17.5% to 26.5% (PBMC original) and from 33.8% to 55.9% (CBMC original); The cytotoxic activity rates against K562 cells by CIK cells were increased from 24.0% to 52.2% (PBMC original) and from 35.1% to 79.7% (CBMC original); The concentration of IFNgamma in the culture supernatant was increased for 1.9-fold (PBMC original), and for 3.2-fold (CBMC original); The cytotoxic activity against K562 cells by the culture supernatant was increased for 1.8-fold (PBMC original) and for 2.7-fold (CBMC original); The expression of IFNgamma RNA in CIK cells was also markedly increased derived from both PBMC and CBMC when cultured with IL-21. Moreover, the cytotoxic activity against leukemia cells from 11 patients (6 with acute lymphoblastic leukemia, 5 with acute myeloid leukemia) by CIK cells derived from CBMC were also detected. The cytotoxic activity rates were at a median of 68.3% (range, 34.7%–86.4%) when CIK cells were cultured with IL-21, rates that contrasted drastically to the cytotoxic activity rates when CIK cells were cultured without IL-21, which were only at a median of 37.4% (range, 16.1%–60.0%). In conclusion, our data indicated that IL-21 could enhance the expansion of CIK cells and their anti-tumor activity derived from both PBMC and CBMC in vitro, IFNgamma was evolved in this course although the mechanism still need to be explored. These observations open up the possibility of imagining a future clinical application of IL-21 in the anti-tumor immunotherapy by CIK cells.

scholarly journals Early suppression of peripheral mononuclear blood cells in sepsis in response to stimulation with cytomegalovirus, OKT3, and pokeweed mitogen

2019 ◽  
Vol 127 (6) ◽  
pp. 1539-1547
Author(s):  
N. M. Malewicz ◽  
K. Walstein ◽  
T. Heine ◽  
A. Engler ◽  
A. Bick ◽  
...  
Keyword(s):  
Blood Cells ◽  
Time Course ◽  
Mononuclear Cells ◽  
Pokeweed Mitogen ◽  
Acquired Immunity ◽  
Peripheral Blood Mononuclear ◽  
Icu Admission ◽  
Early Sepsis ◽  
Mononuclear Blood Cells

Critically ill patients are at risk for sepsis, and immunosuppressive mechanisms may prevail. Whether functional tests are helpful to detect immune alterations is largely unknown. Therefore, we tested the hypotheses that reactivity of peripheral blood mononuclear cells (PBMCs) to secrete interferon-γ (IFNγ) following stimulation in vitro is decreased in patients with early sepsis compared with postoperative patients. IFNγ secretion [enzyme-linked immunospot (ELISpot)] in response to stimulation with cytomegalovirus (CMV), pokeweed mitogen (PWM), muromonab-anti-CD3 (OKT3), and human leukocyte antigen (HLA)-DRA-mRNA expression and serum cytokine concentrations were repeatedly [ days 1, 3, 5, and 7 after intensive care unit (ICU) admission] determined in patients with sepsis ( n = 7) and patients undergoing major abdominal surgery (radical prostatectomy, cystectomy, n = 10). In a second cohort, HLA-DRA expression was assessed in 80 patients with sepsis, 30 postoperative patients, and 44 healthy volunteers (German clinical trials database no. 00007694). In patients with sepsis, IFNγ secretion (ELISpot) was decreased compared with controls after stimulation with CMV ( P = 0.01), OKT3 ( P = 0.02), and PWM ( P = 0.02 on day 5), whereas unstimulated IFNγ secretion did not differ. HLA-DRA expression was also significantly decreased in patients with sepsis at all time points ( P = 0.004) compared with postoperative surgical patients, a finding confirmed in the larger cohort. Reactivity of PBMCs to stimulation with CMV, PWM, and OKT3 as well as HLA-DRA expression was already decreased upon ICU admission in patients with sepsis when compared with postoperative controls, suggesting early depression of acquired immunity. ELISpot assays may help to clinically characterize the time course of immunocompetence in patients with sepsis. NEW & NOTEWORTHY We observed suppression of reactivity to stimulation with cytomegalovirus, muromonab-anti-CD3, and pokeweed mitogen in mononuclear blood cells of patients with early sepsis when compared with postoperative controls. Thus, there is early depression of acquired immunity in sepsis. Enzyme-linked immunospot assays may help to characterize immunocompetence in patients with sepsis.

scholarly journals The Interaction of Selenium with Chemotherapy and Radiation on Normal and Malignant Human Mononuclear Blood Cells

2018 ◽  
Vol 19 (10) ◽  
pp. 3167 ◽  
Author(s):  
Richard Lobb ◽  
Gregory Jacobson ◽  
Ray Cursons ◽  
Michael Jameson
Keyword(s):  
Blood Cells ◽  
Mononuclear Cells ◽  
Malignant Cells ◽  
Cancer Treatments ◽  
Peripheral Blood Mononuclear ◽  
Normal Cells ◽  
Anticancer Properties ◽  
Methylseleninic Acid ◽  
Mononuclear Blood Cells

Selenium, a trace element with anticancer properties, can reduce harmful toxicities of chemotherapy and radiotherapy without compromising efficacy. However, the dose-response relationship in normal versus malignant human cells is unclear. We evaluated how methylseleninic acid (MSA) modulates the toxicity and efficacy of chemotherapy and radiation on malignant and non-malignant human mononuclear blood cells in vitro. We specifically investigated its effects on endoplasmic reticulum stress induction, intracellular glutathione concentration, DNA damage and viability of peripheral blood mononuclear cells and THP1 monocytic leukaemia cells in response to radiation, cytosine arabinoside or doxorubicin chemotherapy. MSA, at lower concentrations, induced protective responses in normal cells but cytotoxic effects in malignant cells, alone and in conjunction with chemotherapy or radiation. However, in normal cells higher concentrations of MSA were directly toxic and increased the cytotoxicity of radiation but not chemotherapy. In malignant cells higher MSA concentrations were generally more effective in combination with cancer treatments. Thus, optimal MSA concentrations differed between normal and malignant cells and treatments. This work supports clinical reports that selenium can significantly reduce dose-limiting toxicities of anticancer therapies and potentially improve efficacy of anticancer treatments. The optimal selenium compound and dose is not yet determined.

scholarly journals Study of the IL-4 and IL-4δ2 interaction with the IL-4R receptors of the I and II types in silico and the effect on the functional activity of mononuclear cells in vitro

2010 ◽  
Vol 9 (3) ◽  
pp. 51-56
Author(s):  
K. V. Goremykin ◽  
A. N. Silkov ◽  
B. V. Shilov ◽  
V. Yu. Serebrov ◽  
A. E. Sazonov ◽  
...  
Keyword(s):  
Blood Cells ◽  
Proliferative Activity ◽  
Mononuclear Cells ◽  
Splice Form ◽  
Antagonistic Effects ◽  
Computer Methods ◽  
Full Form ◽  
Alternatively Spliced ◽  
Mononuclear Blood Cells

Alternatively spliced interleukins are very actively studied over the last years. Splice form of IL-4 — IL-4δ2 has antagonistic effects to its full form on proliferative activity of human mononuclear blood cells and their IL-6 production. Antagonistic effects between IL-4 and IL-4δ2 were confirmed and explained in this study due to combination of biochemical and computer methods.

The Age-Related Rise of Plasma Cholesterol in Humans Is Not Caused by a Cell Removal Defect of LDL Particles: ‘In vitro’ Studies in Peripheral Mononuclear Blood Cells

Gerontology ◽  
1997 ◽  
Vol 43 (4) ◽  
pp. 232-241 ◽  
Author(s):  
Monica Q.T.S. Neves ◽  
Márcia D.T. Carvalho ◽  
Marisa Passarelli ◽  
Edna R. Nakandakare ◽  
Márcia M.M.S. Bernik ◽  
...  
Keyword(s):  
Blood Cells ◽  
Plasma Cholesterol ◽  
In Vitro Studies ◽  
Ldl Particles ◽  
Age Related ◽  
Peripheral Mononuclear Blood ◽  
A Cell ◽  
Mononuclear Blood Cells ◽  
Peripheral Mononuclear Blood Cells

scholarly journals USE OF MICRONUCLEUS EXPERIMENTS FOR THE DETECTION OF HUMAN CANCER RISKS: A BRIEF OVERVIEW

2021 ◽  
Vol 65 (2) ◽  
Author(s):  
Armen Nersesyan ◽  
◽  
Miroslav Mišík ◽  
Andriy Cherkas ◽  
Viktoria Serhiyenko ◽  
...  
Keyword(s):  
Blood Cells ◽  
Environmental Control ◽  
Human Cancer ◽  
Occupational Exposures ◽  
Human Biomonitoring ◽  
Target Cells ◽  
Cancer Risks ◽  
Wide Range

Introduction. Micronuclei (MN) are small extranuclear DNA-containing structures that are formed as a consequence of structural and numerical chromosomal aberrations. The advantage of MN experiments compared to conventional chromosomal analyses in metaphase cells is that the scoring is by far less time consuming and laborious. MN experiments are currently widely used for the routine screening of chemicals in vitro and in vivo but also for environmental control and human biomonitoring Objectives. The purpose of this review was to collect data on the use of MN experiments for the detection of increased cancer risks as a consequence of environmental, lifestyle and occupational exposures and the detection/diagnosis of different forms of cancer. Methods. Analysis of the literature on methods for MN experiments with humans; as well as the use of this technique in different areas of research. Results. To date, a wide range of protocols for human biomonitoring studies has been developed for the measurement of MN formation in peripheral blood cells and in epithelial from different organs (buccal and nasal cavity, cervix and bladder). In addition to MN, other nuclear anomalies can be scored which reflect genetic instability as well as acute toxicity and the division of target cells. Conclusions. The evidence is accumulating that MN can be used as a diagnostic tool for the detection of increased cancer risks as well as for the early diagnosis of cervical and bladder cancer

BTK Inhibitors, Irrespective of ITK Inhibition, Increase Efficacy of a CD19/CD3 Bispecific Antibody in CLL

Blood ◽  
2021 ◽  
Author(s):  
Maissa Mhibik ◽  
Erika M. Gaglione ◽  
David Eik ◽  
Ellen K Kendall ◽  
Amy Blackburn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic Activity ◽  
Kinase Inhibitors ◽  
Bispecific Antibody ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Lymphocytic Leukemia ◽  
Peripheral Blood Mononuclear

Bruton Tyrosine Kinase inhibitors (BTKis) are a preferred treatment for patients with chronic lymphocytic leukemia (CLL). Indefinite therapy with BTKis, while effective, presents clinical challenges. Combination therapy can deepen responses, shorten treatment duration, and possibly prevent or overcome drug resistance. We previously reported on a CD19/CD3 bispecific antibody (bsAb) that recruits autologous T cell cytotoxicity against CLL cells in vitro. Compared to observations with samples from treatment-naïve patients, T cells from patients being treated with ibrutinib expanded more rapidly and exerted superior cytotoxic activity in response to the bsAb. In addition to BTK, ibrutinib also inhibits IL2 inducible T cell Kinase (ITK). In contrast, acalabrutinib, does not inhibit ITK. Whether ITK inhibition contributes to the observed immune effects is unknown. To better understand how BTKis modulate T-cell function and cytotoxic activity, we cultured peripheral blood mononuclear cells (PBMCs) from BTKi-naive, and ibrutinib- or acalabrutinib-treated CLL patients with CD19/CD3 bsAb in vitro. T-cell expansion, activation, differentiation, and cytotoxicity were increased in PBMCs from patients on treatment with either BTKi compared to that observed for BKTi-naïve patients. BTKi therapy transcriptionally downregulated immunosuppressive effectors expressed by CLL cells, including CTLA-4 and CD200. CTLA-4 blockade with ipilimumab in vitro increased the cytotoxic activity of the bsAb in BTKi-naïve but not BTKi-treated PBMCS. Taken together, BTKis enhance bsAb induced cytotoxicity by relieving T cells of immunosuppressive restraints imposed by CLL cells. The benefit of combining bsAb immunotherapy with BTKis needs to be confirmed in clinical trials.

scholarly journals Surface membrane vesicles from mononuclear cells stimulate erythroid stem cells to proliferate in culture

Blood ◽  
1982 ◽  
Vol 60 (3) ◽  
pp. 583-594 ◽  
Author(s):  
N Dainiak ◽  
CM Cohen
Keyword(s):  
Plasma Membrane ◽  
Plasma Membranes ◽  
Mononuclear Cells ◽  
Surface Membrane ◽  
Freeze Fracture ◽  
Membrane Vesicles ◽  
Cell Types ◽  
Target Cells ◽  
Freeze Fracture Electron Microscopy

Abstract In order to examine the contribution of cell surface materials to erythroid burst-promoting activity (BPA), we separated media conditioned by a variety of human cell types into pellets and supernatants by centrifugation. When added to serum-restricted cultures of nonadherent human marrow cells, pellets contained about half of the total stimulatory activity. Freeze-fracture electron microscopy of the pellets revealed the presence of unilamellar membrane vesicles ranging from 0.10 to 0.40 microM in diameter. The amount of BPA in culture increased with added vesicle concentration in a saturable fashion. Preparation of leukocyte conditioned medium (LCM) from 125I-wheat germ agglutinin labeled cells and studies comparing the glycoprotein composition of vesicles with that of leukocyte plasma membranes suggest that LCM-derived vesicles are of plasma membrane origin. Moreover, partially purified leukocyte plasma membrane preparations also contained BPA. While disruption of vesicles by freezing/thawing and hypotonic lysis did not alter BPA, heat, trypsin, or pronase treatment removed greater than 65% of BPA, implying that vesicle surface rather than intravesicular molecules express BPA. Results of BPA assays performed in two-layer clots indicated that proximity to target cells is required for vesicle BPA expression. We conclude that membrane vesicles spontaneously shed from cell surfaces may be important regulators of erythroid burst proliferation in vitro.

scholarly journals Cytotoxic Effect of Trabectedin In Human Adrenocortical Carcinoma Cell Lines and Primary Cells

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 928 ◽  
Author(s):  
Andrea Abate ◽  
Elisa Rossini ◽  
Sara Anna Bonini ◽  
Martina Fragni ◽  
Deborah Cosentini ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cell Cultures ◽  
Adrenocortical Carcinoma ◽  
Cytotoxic Effect ◽  
Alkylating Agents ◽  
Primary Cell ◽  
Primary Cell Cultures ◽  
High Cytotoxicity

Mitotane is the only drug approved for the treatment of adrenocortical carcinoma (ACC). The regimen to be added to mitotane is a chemotherapy including etoposide, doxorubicin, and cisplatin. This pharmacological approach, however, has a limited efficacy and significant toxicity. Evidence indicates that ACC seems to be sensitive to alkylating agents. Trabectedin is an anti-tumor drug that acts as an alkylating agent with a complex mechanism of action. Here, we investigated whether trabectedin could exert a cytotoxic activity in in vitro cell models of ACC. Cell viability was evaluated by MTT assay on ACC cell lines and primary cell cultures. The gene expression was evaluated by q-RT-PCR, while protein expression and localization were studied by Western blot and immunocytochemistry. Combination experiments were performed to evaluate their interaction on ACC cell line viability. Trabectedin demonstrated high cytotoxicity at sub-nanomolar concentrations in ACC cell lines and patient-derived primary cell cultures. The drug was able to reduce /β catenin nuclear localization, although it is unclear whether this effect is involved in the observed cytotoxicity. Trabectedin/mitotane combination exerted a synergic cytotoxic effect in NCI-H295R cells. Trabectedin has antineoplastic activity in ACC cells. The synergistic cytotoxic activity of trabectedin with mitotane provides the rationale for testing this combination in a clinical study.

Sign in / Sign up

Export Citation Format

Share Document