Cytokines as potential combination agents with PD-1/PD-L1 blockade for cancer treatment.

Immunotherapy has caused a paradigm shift in the treatment of several malignancies, particularly the blockade of programmed death-1 (PD-1) and its specific receptor/ligand PD-L1 that have revolutionized the treatment of a variety of malignancies, but significant durable responses only occur in a small percentage of patients, and other patients failed to respond to the treatment. Even those who initially respond can ultimately relapse despite maintenance treatment, there is considerable potential for synergistic combinations of immunotherapy and chemotherapy agents with immune checkpoint inhibitors into conventional cancer treatments. The clinical experience in the use of cytokines in the clinical setting indicated the efficiency of cytokine therapy in cancer immunotherapy. Combinational approaches to enhancing PD-L1/PD-1 pathways blockade efficacy with several cytokines such as interleukin (IL)-2, IL-15, IL-21, IL-12, IL-10, and interferon-α (IFN-α) may result in additional benefits. In this review, the current state of knowledge about PD-1/PD-L1 inhibitors, the date in the literature to ascertain the combination of anti-PD-1/PD-L1 antibodies with cytokines is discussed. Finally, it is noteworthy that novel therapeutic approaches based on the efficient combination of recombinant cytokines with the PD-L1/PD-1 blockade therapy can enhance antitumor immune responses against various malignancies.

Anticancer properties of green-synthesised zinc oxide nanoparticles using Hyssopus officinalis extract on prostate carcinoma cells and its effects on testicular damage and spermatogenesis in Balb/C mice.

The unclear bio-safety issue and potential risk of nanoparticles (NPs) on various organelles can be considered as a major challenge. In the present study, we have assessed the green synthesis of ZnO nanoparticles using Hyssop (Hyssopus officinalis) extract and their effects on PC3 cell line and BALB/c mice model. The cytotoxicity of the ZnO-NPs was assessed on PC3 cell line by MTT test after characterisation. Apoptotic effect of ZnO-NPs was determined by in vitro AO/PI staining. The histopathological assessments and determination of LH and FSH levels carried out as in vivo analysis in BALB/c adult male mice. The expression of major genes involved in spermatogenesis and sperm maturation (Adam3, Prm1, Spata19, Tnp2, Gpx5) were also analysed. The obtained result demonstrated that the IC50 for PC3 cell line treated with green-synthesised ZnO-NPs during 24 and 48 hr was reported 8.07 and 5 µg/ml respectively. Meanwhile, the induced apoptosis was recorded 26.6% ± 0.05, 44% ± 0.12 and 80% ± 0.07 of PC3 cells. The results of gene expression analysis revealed that the increase in the concentration of ZnO-NPs significantly (p < .05) down-regulated the Adam3, Prm1, Spata-19, Tnp2 and Gpx5 genes. The overall results of this research elucidated that ZnO-NPs impaired spermatogenesis, sperm maturation process and sperm motility.

The cytotoxic properties of zinc oxide nanoparticles on the rat liver and spleen, and its anticancer impacts on human liver cancer cell lines.

INTRODUCTION: Due to their unique properties including cellular uptake and the delivery efficiency to biological systems, nanoparticles are used in various preclinical and clinical applications. The aim of this study was to investigate the toxicity impacts of zinc oxide nanoparticles (ZnO-NPs) on morphology and functionality of the rat's liver and spleen and illustrated its safe-therapeutic doses. METHODS: The 28 female Swiss albino rats (180-220 g) and two human hepatocyte cell lines (HepG2 and HUH7) were designed as an in vivo and in vitro study, respectively. Samples were treated with certain doses of ZnO-NPs. The rat's liver morphology and functionality and apoptotic genes expression profile (Bax, Bcl-2, and P53) were analyzed to detect the cytotoxicity and antitumor impacts of ZnO-NPs, respectively. RESULTS: The results showed a positive significant association between the increasing doses of ZnO-NPs and alanine aminotransferase/aspartate aminotransferase values. Moreover, a meaningful correlation was detected between the rat's liver and spleen weight and ZnO-NPs doses. Furthermore, the histopathological analysis of rat's liver showed the individual cytotoxic properties of ZnO-NPs. Finally, the positive significant correlation was detected among the expression of Bax and P53 genes with ZnO-NPs. In addition, the negative correlation was demonstrated between the expression of Bcl-2 and ZnO-NPs. CONCLUSION: In general, in the current study, the antitumor effects of ZnO-NPs were confirmed by the enhancement of P53 and Bax genes expression profile, which are indicated the apoptotic induction in HUH7 cell line. Moreover, we introduced a safe-clinical ZnO-NPs dosage, have antitumor effects.

Urolithin B loaded in cerium oxide nanoparticles enhances the anti-glioblastoma effects of free urolithin B in vitro.

Glioblastoma multiforme (GBM) is the most aggressive kind of malignant primary brain tumor in humans. Given the limitation of Conventional therapeutic strategy, the development of nanotechnology and natural product therapy seems to be an effective method enhancing the prognosis of GBM patients. In this research, cell viability, mRNA expressions of various apoptosis-related genes apoptosis, and generation of reactive oxygen species (ROS) in human U-87 malignant GBM cell line (U87) treated with Urolithin B (UB) and CeO2-UB. Unlike CeO2-NPs, both UB and CeO2-UB caused a dose-dependent decrease in the viability of U87 cells. The half-maximal inhibitory concentration values of UB and CeO2-UB were 315 and 250 µM after 24 h, respectively. Moreover, CeO2-UB exerted significantly higher effects on U87 viability, P53 expression, and ROS generation. Furthermore, UB and CeO2-UB increased the accumulation of U87 cells in the SUB-G1 population, decreased the expression of cyclin D1, and increased the Bax/Bcl2 ratio expression. Collectively, these data indicate that CeO2-UB exhibited more substantial anti-GBM effects than UB. Although further in vivo investigations are needed, these results proposed that CeO2-NPs could be utilized as a potential novel anti-GBM agent after further studies.

Biosynthesis of zinc oxide nanoparticles using anjbar (root of Persicaria bistorta) extract and their cytotoxic effects on human breast cancer cell line (MCF-7).

Biosynthesis of nanoparticles (NPs) using biomass is now one of the best methods for synthesising NPs due to their nontoxic and biocompatibility. Plants are the best choice among all biomass to synthesise large-scale NPs. The objectives of this study were to synthesise zinc oxide nanoparticles (ZnO-NPs) using Anjbar (root of Persicaria bistorta) [An/ZnO-NPs] and investigate the cytotoxic and anti-oxidant effects. For this purpose, the An/ZnO-NPs were synthesised by using Bistort extract and characterised using UV-Visible spectroscopy, transmission electron microscope, field emission scanning electron microscope, x-ray diffraction and Fourier-transform infrared spectroscopy. The cytotoxic effects of the An/ZnO-NPs on MCF-7 cells were followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays at 24, 48, and 72 h. Nuclear morphology changed and apoptosis in cells was investigated using acridine orange/propodium iodide (AO/PI) staining and flow cytometry analysis. The pure biosynthesised ZnO-NPs were spherical in shape and particles sizes ranged from 1 to 50 nm. Treated MCF-7 cells with different concentrations of ZnO-NPs inhibited cell viability in a time- and dose-dependent manner with IC50 about 32 µg/ml after 48 h of incubation. In flow cytometry analysis the sub-G1 population, which indicated apoptotic cells, increased from 12.6% at 0 µg/ml (control) to 92.8% at 60 µg/ml, 48 h after exposure. AO/PI staining showed that the treated cells displayed morphologic evidence of apoptosis, compared to untreated groups.