The cytogenetic evaluation of in vivo genotoxic and cytotoxic activity using rodent somatic cells

1988 ◽  
Vol 4 (4) ◽  
pp. 475-486 ◽  
Author(s):  
Raymond R. Tice
Keyword(s):  
Cytotoxic Activity ◽  
Somatic Cells

scholarly journals Specific antioxidant compounds differentially modulate cytotoxic activity of doxorubicin and cisplatin: in vitro and in vivo study

2014 ◽  
Vol 55 (3) ◽  
pp. 206-217 ◽  
Author(s):  
Rostyslav Panchuk ◽  
Nadia Skorokhyd ◽  
Vira Chumak ◽  
Lilya Lehka ◽  
Sofya Omelyanchik ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
In Vivo Study ◽  
Antioxidant Compounds

scholarly journals Small Molecule Screening Identifies Rho-Associate Protein Kinase (ROCK) As a Regulator of NK Cell Cytotoxicity Against Cancer

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3607-3607
Author(s):  
Grace Lee ◽  
Sheela Karunanithi ◽  
Zachary Jackson ◽  
David Wald
Keyword(s):  
Cell Therapy ◽  
Cytotoxic Activity ◽  
Nk Cells ◽  
Nk Cell ◽  
Ex Vivo ◽  
Akt Activation ◽  
Nk Cell Cytotoxicity ◽  
Rock Inhibition ◽  
Nk Cell Therapy

NK cells are a subset of lymphocytes that directly recognize and lyse tumor cells without the limitation of antigen specific receptor recognition. In addition to behaving as cytotoxic effector cells, NK cells unlike T cells are not thought to elicit graft versus host disease. The combination of these characteristics makes NK cells a powerful tool for adoptive cell therapy. Despite the promise of NK cell therapy, key hurdles in achieving significant clinical efficacy include both generating sufficient numbers of highly tumoricidal NK cells and maintaining the cytotoxic activity of these cells in vivo despite the immunosuppressive tumor microenvironment. Our lab and others have developed several feeder cell line-based expansion modules that robustly stimulate the ex vivo proliferation of NK cells. However, strategies to enhance and sustain the activity of NK cells once administered in vivo are still limited. In order to identify strategies to enhance the cytotoxic activity of NK cells, we developed a high-throughput small molecule screen (Figure 1A) that involved a calcein-based cytotoxicity assay of ex vivo expanded and treated NK cells against ovarian cancer cells (OVCAR-3). 20,000 compounds were screened and the screen was found to be highly robust (Z'>0.59). We identified 29 hits that led to at least a 25% increase in cytotoxicity as compared to DMSO control-treated NK cells. One of the most promising hits was the pan-ROCK inhibitor, Y-27632 that led to an 30% increase in NK killing of the OVCAR-3 cells. We validated that ROCK inhibition leads to enhanced NK cell cytotoxic activity using Y-27632 (Figure 1B) as well as other well-established ROCK inhibitors such as Fasudil using a flow cytometry based killing assay. Y-27632 increased NK cell cytotoxicity in a dose- and time- dependent manner. ROCK inhibition consistently led to ~10-25% increase in NK cell cytotoxic activity directed against a variety of ovarian (Figure 1C) and other solid tumor cell lines (Figure 1D). Interestingly, we found that the NK hyperactivation persists for up to 48hrs after washing off the drug that may enable ex vivo stimulation before NK cell infusion. Our preliminary results showed that ROCK inhibition activates PI3K-dependent Akt activation (Figure 1E). We hypothesize that ROCK inhibition restores Akt activation which may be critical for NK cell activating receptor pathways and our current investigations will test these hypotheses. ROCK inhibitors, such as Y-27632 and Fasudil have been utilized in both preclinical and clinical studies for a variety of diseases such as atherosclerosis, neurodegenerative disorders, and ocular diseases. However, the consequences of ROCK inhibition in NK cells has not been thoroughly investigated. Our work shows a promising novel strategy to significantly enhance NK cell therapy against cancer that has high translational potential. Disclosures No relevant conflicts of interest to declare.

scholarly journals Flavonoids content of 70% methanolic extract of Erucaria pinnata (Viv.) and its effect as anticancer and antiangiognic: in vitro, in vivo and docking study

2020 ◽  
Vol 11 (1) ◽  
pp. 25-38
Author(s):  
Nadia I. Zakhary ◽  
Emad E.H. El Gemeie ◽  
Adel K. Youssef ◽  
Marwa Abdel-salam Ibrahim Metwaly
Keyword(s):  
Cytotoxic Activity ◽  
Methanolic Extract ◽  
Coastal Region ◽  
Experimental Period ◽  
Docking Study ◽  
Gamma Glutamyl Transferase ◽  
Histopathological Studies ◽  
Glutamyl Transferase

Erucaria pinnata (Viv.) is a wild annual plant growing in North-Western Coastal Region in Egypt. This study reports for the first time the cytotoxic activity of different extracts of Erucaria pinnata plant against HEP-G2 cell line. The 70% methanolic extract (E1) recorded the best potent cytotoxic activity (IC50=13.6 µg/ml), so we analysis the flavonoids constituent of this extract using HPLC, which show that our extract is rich with important flavonoids compounds (rutin, quercetin, leutolin, etc.). We evaluated its antitumor activity against hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) (200mg/Kg. b.wt., i.p, single dose) after two weeks, animals received carbontetrachloride (CCl4) (3ml/Kg. b.wt., SC, once a week for 6 weeks) and the experiment continued for 44 weeks in rats. After the experimental period, the administration of DEN/CCl4 showed significant increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, gamma-glutamyl transferase (γGT) and significant decrease in the levels of total proteins and albumin content in the serum with reduction in the liver antioxidants, including superoxide dismutase (SOD) and catalase (CAT). This was accompanied by increases in serum specific tumor markers (AFP). The 70% methanolic plant extract (E1) was orally administrated (400mg/kg/day respectively) for the whole study period, and it showed a significant improvement at the different biological liver functions, remodeled the antioxidant enzymes activity and down-regulated the serum AFP. All these findings were confirmed by histopathological studies of the liver samples obtained from all groups. In addition, we evaluated its antiangeogenic activity by docking study against VEGFR-2 tyrosine kinase after it showed an ability to inhibit the VEGFR-2 expression in vitro and inhibit the concentration of VEGF-A in vivo. The hepatoprotective effect of our extract was attributed to its antioxidant and antiangeogenic activity.

scholarly journals The Advantages and Challenges of Anticancer Dendritic Cell Vaccines and NK Cells in Adoptive Cell Immunotherapy

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1363
Author(s):  
Elena V. Abakushina ◽  
Liubov I. Popova ◽  
Andrey A. Zamyatnin ◽  
Jens Werner ◽  
Nikolay V. Mikhailovsky ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Nk Cells ◽  
Nk Cell ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Adoptive Cell Therapy ◽  
Immune Effector ◽  
Effector Cells ◽  
Cell Immunotherapy

In the last decade, an impressive advance was achieved in adoptive cell therapy (ACT), which has improved therapeutic potential and significant value in promising cancer treatment for patients. The ACT is based on the cell transfer of dendritic cells (DCs) and/or immune effector cells. DCs are often used as vaccine carriers or antigen-presenting cells (APCs) to prime naive T cells ex vivo or in vivo. Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are used as major tool effector cells for ACT. Despite the fact that NK cell immunotherapy is highly effective and promising against many cancer types, there are still some limitations, including insignificant infiltration, adverse conditions of the microenvironment, the immunosuppressive cellular populations, and the low cytotoxic activity in solid tumors. To overcome these difficulties, novel methods of NK cell isolation, expansion, and stimulation of cytotoxic activity should be designed. In this review, we discuss the basic characteristics of DC vaccines and NK cells as potential adoptive cell preparations in cancer therapy.

scholarly journals Synthesis, Characterization and Cytotoxic Activity of N-(5-indanyl(methylene)anthranilic acid(5-indanyl methylene)-hydrazide and Its Pt(II) Complex

2019 ◽  
pp. 1-12
Author(s):  
Nasser Mohammed Hosny ◽  
Lamiaa A. A. Barakat
Keyword(s):  
Cytotoxic Activity ◽  
Anthranilic Acid ◽  
Platinum Complex ◽  
Platinum Complexes ◽  
Ehrlich Ascites Carcinoma ◽  
Morphological Characterization ◽  
Spherical Particles ◽  
Spectral Techniques ◽  
Average Size

Since the discovery of the platinum based complex, cisplatin, medicinal inorganic chemistry has attracted much more attention and a large number of platinum complexes with promising pharmacological properties have been synthesized. In this work a new platinum complex of N-(5-indanyl(methylene)anthranilic acid(5-indanyl methylene)-hydrazide (HL) has been synthesized and characterized by physical and spectral techniques, as elemental analysis, IR, EI-MS, 1H-NMR, thermal analysis, transmittance electron microscope (TEM) and magnetic moment. The results indicated that the ligand binds to Pt(II) in the enol form. Square-planar stereochemistry was suggested for the Pt(II) complex. The morphological characterization showed nano-sized spherical particles with average size 92 nm of the isolated complex. The synthesized Pt(II) complex exhibited a significant cytotoxic activity against HCT116 and HEPG2. Also in vivo study of the Pt(II) complex showed cytotoxic activity towards Ehrlich ascites carcinoma (EAC).

Anti-nociceptive and anti-inflammatory activity of synthesized novel benzoxazole derivatives

2021 ◽  
Vol 20 ◽  
Author(s):  
Mansi L. Patil ◽  
Swati S. Gaikwad ◽  
Naresh J. Gaikwad
Keyword(s):  
Cytotoxic Activity ◽  
Research Study ◽  
Ex Vivo ◽  
Immunological Response ◽  
Inflammatory Activity ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Introduction: Pain is an immunological response to any infection or inflammation and long term use of pain management therapy includes use of Nonsteroidal anti-inflammatory drugs which is associated with occurrence of toxicity as well as gastrointestinal bleeding. Therefore, the investigation of new analgesic and anti-inflammatory agents remains a major challenge. Aims: The objective of this research study is to undergo the pharmacological evaluation of newly synthesized benzoxazole derivatives. These novel derivatives were evaluated for anti-nociceptive, anti-inflammatory and cytotoxic activity using various in-vivo and ex-vivo methods. Methods: The study was carried out using swiss mice (adult male) weighing between 20gm to 30gm and were divided into groups containing (n=6) six animals in each group for treatment. The anti-nociceptive activity was performed by using 0.1ml of 0.6% v/v acetic acid as nociception inducer and evaluated by the diminished number of abdominal writhes. The anti-inflammatory activity was done using 0.1 ml of 2% w/v Carrageenan induced paw edema method was observed which was evaluated by calculating the percent maximum possible effect. Histopathological evaluation and cytotoxic activity of the compounds was carried out. Results: The results of this research study revealed that synthesized derivatives (a, b, c, d and e) showed promising anti-nociceptive and anti-inflammatory effect along significantly higher cytotoxic activity in MCF-7 cell lines. Conclusion: It can be concluded that synthesized derivatives (a, b, c, d and e) have potential anti-nociceptive and anti-inflammatory effect along with cytotoxic activity and certain modification in structure may result in potent activity.

scholarly journals Gene expression of the heat stress response in bovine peripheral white blood cells and milk somatic cells in vivo

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
J. B. Garner ◽  
A. J. Chamberlain ◽  
C. Vander Jagt ◽  
T. T. T. Nguyen ◽  
B. A. Mason ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heat Stress ◽  
Blood Cells ◽  
White Blood Cells ◽  
Somatic Cells ◽  
Holstein Friesian ◽  
Milk Somatic Cells ◽  
Peripheral White Blood Cells ◽  
Friesian Cows

Abstract Heat stress in dairy cattle leads to reduction in feed intake and milk production as well as the induction of many physiological stress responses. The genes implicated in the response to heat stress in vivo are not well characterised. With the aim of identifying such genes, an experiment was conducted to perform differential gene expression in peripheral white blood cells and milk somatic cells in vivo in 6 Holstein Friesian cows in thermoneutral conditions and in 6 Holstein Friesian cows exposed to a short-term moderate heat challenge. RNA sequences from peripheral white blood cells and milk somatic cells were used to quantify full transcriptome gene expression. Genes commonly differentially expressed (DE) in both the peripheral white blood cells and in milk somatic cells were associated with the cellular stress response, apoptosis, oxidative stress and glucose metabolism. Genes DE in peripheral white blood cells of cows exposed to the heat challenge compared to the thermoneutral control were related to inflammation, lipid metabolism, carbohydrate metabolism and the cardiovascular system. Genes DE in milk somatic cells compared to the thermoneutral control were involved in the response to stress, thermoregulation and vasodilation. These findings provide new insights into the cellular adaptations induced during the response to short term moderate heat stress in dairy cattle and identify potential candidate genes (BDKRB1 and SNORA19) for future research.

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