Resistance Improvement and Sensitivity Enhancement of Cancer Therapy by a Novel Antitumor Candidate onto A2780 CP and A2780 S Cell Lines.

Background: To overcome cisplatin resistance, the cytotoxicity of a novel antitumor agent on two ovarian cancer cell lines sensitive and resistant to cisplatin was investigated. Methods: MTT assay and flow cytometry were performed to assess the cytotoxicity of a novel water-soluble Pd (II) complex, [Pd(bpy)(pyr-dtc)]NO3 (PBPD), on cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines. Furthermore, variations in the expression of drug resistance gene cluster of differentiation 99 (CD99), signal transducer and activator of transcription 3 (STAT3), octamer-binding transcription factor 4 (OCT4), and multidrug resistance mutation 1 (MDR1) were evaluated using Real-Time PCR. Results: The IC50 values of PBPD in resistant cells were higher than those in sensitive cells. Furthermore, PBPD has a deadlier effect on sensitive cells compared to resistant cells, and the cell survival rate is reduced over time. Flow cytometry revealed that PBPD enhanced the population of living-resistant cells while driving them to apoptosis. PBPD, on the other hand, has a greater effect on the living cell population and has dramatically shifted the population toward apoptosis and necrosis in the sensitive cells. Furthermore, gene expression analysis showed that when sensitive and resistant cells were treated with cisplatin, all resistance genes increased significantly relative to the control. In contrast to OCT4, MDR1, STAT3, and CD99 resistance genes were not significantly elevated in sensitive cells treated with PBPD compared to the control. Thus, the expression of resistance genes in resistant cells treated with PBPD was lower than cisplatin. Conclusions: As a result, PBPD is a promising anticancer agent for CDDP-resistant ovarian cancer.

Sol-Gel Synthesis, in vitro Behavior, and Human Bone Marrow-Derived Mesenchymal Stem Cell Differentiation and Proliferation of Bioactive Glass 58S.

Background: Bioactive glasses 58S, are silicate-based materials containing calcium and phosphate, which dissolved in body fluid and bond to the bone tissue. This type of bioactive glass is highly biocompatible and has a wide range of clinical applications. Methods: The 58S glass powders were synthesized via sol-gel methods, using tetraethyl orthosilicate, triethyl phosphate, and calcium nitrate, as precursors. Upon the analyses of phase and chemical structures of bioactive glass in different gelation times (12, 48, and 100 h), the appropriate heat treatment (at 525, 575, and 625 °C) was performed to eliminate nitrate compounds and stabilize the glass powder samples. The in vitro assay in SBF solution revealed the bioactivity of the synthesized 58S glass through the morphological (SEM), chemical structure (FTIR), release of calcium, phosphorous and silicon elements, pH variations, and weight loss measurements. The behavior of MSCs in the presence of bioactive glass powders was studied by MTT cytotoxicity, cell staining, ALP activity and biomineralization tests, as well as by the evaluation of ALP, osteocalcin, osteonectin, collagen I, and RUNX2 gene expression. Results: The results confirmed a gelation time of 100 h and a calcination temperature of 575 °C at optimal conditions for the synthesis of nitrate-free bioactive glass powders. Conclusion: The glass spherical nanoparticles in the range of 20-30 nm possess the improved bioactivity and osteogenic properties as demanded for bone tissue engineering.

Blooming gelatin: an individual additive for enhancing nanoapatite precipitation, physical properties, and osteoblastic responses of nanostructured macroporous calcium phosphate bone cements.

In recent years, there has been a great interest in using natural polymers in the composition of calcium phosphate bone cements to enhance their physical, mechanical, and biological performance. Gelatin is a partially hydrolyzed form of collagen, a natural component of bone matrix. In this study, the effect of blooming gelatin on the nanohydroxyapatite precipitation, physical and mechanical properties, and cellular responses of a calcium phosphate bone cement (CPC) was investigated. Various concentrations of blooming gelatin (2, 5, and 8 wt.%) were used as the cement liquid and an equimolar mixture of tetracalcium phosphate and dicalcium phosphate was used as solid phase. The CPC without any gelatin additive was also evaluated as a control group. The results showed that gelatin accelerated hydraulic reactions of the cement paste, in which the reactants were immediately converted into nanostructured apatite precipitates after hardening. Gelatin molecules induced 4%-10% macropores (10-300 µm) into the cement structure, decreased initial setting time by ~190%, and improved mechanical strength of the as-set cement. Variation in the above-mentioned properties was influenced by the gelatin concentration and progressed with increasing the gelatin content. The numbers of the G-292 osteoblastic cells on gelatin-containing CPCs were higher than the control group at entire culture times (1-14 days), meanwhile better alkaline phosphatase (ALP) activity was determined using blooming gelatin additive. The observation of cell morphologies on the cement surfaces revealed an appropriate cell attachment with extended cell membranes on the cements. Overall, adding gelatin to the composition of CPC improved the handling characteristics such as setting time and mechanical properties, enhanced nanoapatite precipitation, and augmented the early cell proliferation rate and ALP activity.