BackgroundCaspase-3 and granzyme B were claimed as apoptotic manipulative enzymes.AimsThe present study was to determine the enzymes expression and activity in cancer and cancer immune therapeutic status and the possible association to cancer common pathological signs targeting the improvement of therapeutic conditions.Material and MethodsMice were immunized with cell lyaste or cell lysate + CKI in the right thigh and challenged with live cells of ehrlich ascites carcinoma (EAC) in the left thigh. The expression and activity of both enzymes in the spleenocytes derived from different subjects (normal, EAC and cell lysate or cell lysate + CKI immunized mice) after cultured with EAC viable cells were determined by colorimetric assay and western blot analysis. In addition, the subjects DNA ladder and serum metalloproteases (MMP 2 and 9) zymography were observed.ResultsThe experimental data revealed over expression of caspase3 and granzyme B in the groups of cell lysate or cell lysate + CKI immunized mice compared to control while down expression were recorded in the EAC subject. The over expression of the 2 enzymes were accompanied with increases in the activities of caspase3 and granzyme B, changes in DNA fragmentation and inhibition of metalloproteases.ConclusionIt could be suggested that, the parameter estimation within the present experimental framework could identify the efficiency of therapeutic vaccine protocols and elucidate the impact of CKI adjuvant with vaccines therapy.

Purpose Gemcitabine (GEM) is a deoxycytidine analog chemotherapeutic drug widely used for the treatment of many cancers. Silver nanoparticles (AgNPs) are important nanomaterials used in the treatment of many diseases such as infectious diseases. Using gamma radiation in nanoparticle preparation is a new eco-friendly method. This study aims to evaluate the efficency of the co-treatment of gemcitabine and silver nanoparticles in hepatocellular carcinoma treatment. Methods AgNPs characterization has been done using UV- visible spectroscopy, XRD, TEM, and EDX. Firstly, the MTT cytotoxicity in vitro assay of gemcitabine, doxorubicin, and cyclophosphamide was assessed against Wi38 normal fibroblast and HepG2 HCC cell lines. Then after HCC development, rats received (10µg/g b.wt.) of AgNPs three times a week for four weeks and/or GEM (5mg/kg b.wt.) twice weekly for four weeks. Liver function enzymes were investigated. Cytochrome P450 and miR-21 genes were studied. Apoptosis was determined by using flow cytometry, and apoptotic modifications in signaling pathways were evaluated via Bcl-2, Bax, Caspase-9, and SMAD-4. Results The co-treatment of GEM and AgNPs showed upregulation of apoptosis by increasing Bax and caspase 9 while diminishing Bcl2 and SMAD4, amelioration of cytochrome P450 m-RNA relative expression. In addition, the results proved the cooperative effect of GEM and AgNPs in the deactivation of miR21. Conclusion The impact of AgNPs as an adjuvant treatment with GEM was recognized. The interaction between AgNPs and Gem can diminish some of the drawbacks of using GEM alone and elevate its efficiency in HCC treatment via enhancing intrinsic and extrinsic apoptotic pathways.

Using silver nanoparticles is a promising tactic in healthcare and cancer therapy, either alone or as an adjuvant in traditional chemotherapy. In addition, using gamma radiation in nanoparticles preparation is simple, powerful, and environmentally friendly. The present study aims at assessing the impact of silver nanoparticles (AgNPs) prepared by gamma radiation (γ-radiation) on hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN). MTT Cytotoxicity assay of AgNPs has been detected in vitro on Wi38 normal fibroblast and HepG2 hepatocellular carcinoma cell lines. Twenty-eight adult male albino rats were divided into four groups. After HCC development, rats received (10µg/g b. wt.) of AgNPs, three times a week for four weeks. Liver enzymes were investigated. TNF-α, TGF-β, and IL-1β inflammatory markers were detected. Furthermore, the transcriptional factor (NF-κB) was assayed. The obtained results confirmed the selective influence of AgNPs on the HCC cell line in a time and dosedependent manner. Moreover, the role of AgNPs is documented in diminishing the inflammation accompanied by HCC development through decreased inflammatory markers and increased apoptosis.

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