The extract of pomegranate (Punica granatum) has been applied in medicine since ancient times due to its broad-spectrum health-beneficial properties. It is a rich source of hydrolyzable tannins and anthocyanins, exhibiting strong antioxidative, anti-inflammatory, and antineoplastic properties. Anticancer activities of pomegranate with reference to modulated signaling pathways in various cancer diseases have been recently reviewed. However, less is known about punicalagin (Pug), a prevailing compound in pomegranate, seemingly responsible for its most beneficial properties. In this review, the newest data derived from recent scientific reports addressing Pug impact on neoplastic cells are summarized and discussed. Its attenuating effect on signaling circuits promoting cancer growth and invasion is depicted. The Pug-induced redirection of signal-transduction pathways from survival and proliferation into cell-cycle arrest, apoptosis, senescence, and autophagy (thus compromising neoplastic progression) is delineated. Considerations presented in this review are based mainly on data obtained from in vitro cell line models and concern the influence of Pug on human cervical, ovarian, breast, lung, thyroid, colorectal, central nervous system, bone, as well as other cancer types.
The surface effects on the critical dimensions of ferromagnetic nanoparticles have been studied. Iron nanoparticles with different mean diameter from 5.9 nm to 21.4 nm were prepared by thermal decomposition of iron pentacarbonyl in the presence of oleic acid/octyl ether. The heating response of these ferromagnetic nanoparticles suspended in water were measured experimentally during which the same amount of iron nanoparticles and di-ionized water were irradiated by an alternating magnetic field and the increase in temperature of the system was measured. The heating performance of the nanoparticles was described in terms of Specific Absorption Rate (SAR) which depends on the heating rate. The heating rate was calculated from the initial slope of the heating curve at an inflection point whereby there is minimum heat loss to the surrounding. Results were analyzed to find the critical diameters for the transition from single-domain to superparamagnetic regime and from single-domain to multi-domain regime. Also, the frequency and current dependence of SAR were studied. The maximum value of SAR was obtained when the applied frequency and current were at 175 kHz and 15 A, respectively. An equation for the critical radius for the transition from single-domain to multi-domain regime with low anisotropy was derived and numerically solved by using a program written in C++ and results were analyzed to find the effect of surface parameters on the critical diameter of nanoparticles. The SAR as a function of nanoparticle’s diameter shows two maxima which can be connected with the two critical dimensions. One is D C1 at 18 nm for the transition from single-domain to multi-domain configuration and the second is D C2 at 10 nm for the transition from single-domain to superparamagnetic regime. Comparison of these experimental results with the bond order-length-strength correlation theory was discussed.
To evaluate clinical significance and diagnostic utility of increase in serum PDGF-BB (sPDGF-BB) in esophageal cancer, which have not been addressed yet despite the relevance of PDGF axis in this cancer type.Immunoenzymatically assessed sPDGFBB was related to clinicopathological features, and inflammatory, angiogenic, and lymphangiogenic indices in 84 patients with esophageal cancer and 47 controls. Its diagnostic utility was evaluated by receiver operating characteristics (ROC) curve analysis.sPDGF-BB was significantly higher in esophageal cancer patients than controls (3.76 vs. 2.66 μg/l, p = 0.0001) and corresponded with the disease advancement. Of evaluated clinicopathological features, lymph node metastases and distant metastases were independently associated with an increase in sPDGF-BB; however, only the association with lymph node metastases persist adjustment to platelets. In univariate analysis, sPDGF positively correlated with platelets (r=0.70, p < 0.0001), vascular endothelial growth factor (VEGF)-A (r=0.50, p < 0.0001), VEGF-C (r=0.57, p < 0.0001), white blood cells (r=0.32, p = 0.004), C-reactive protein (r=0.34, p = 0.004), IL-6 (r=0.35, p = 0.003), and IL-8 (r=0.45, p < 0.0001). In multivariate analysis, VEGF-C and platelets were independently associated with sPDGF-BB explaining 61% in its variability. With >2.845 μg/l cut-off, over 76% of patients had elevated sPDGF-BB. Its accuracy as lymph node metastases marker was 75%, sensitivity and specificity corresponding with >3.029 μg/l cut-off were 84 and 61%, respectively.sPDGF-BB owns potential as a possible lymph node metastases marker and might be considered as a diagnostic tool in preliminary evaluation of esophageal cancer patients identifying those likely to be burdened with lymph node metastases, the disease recurrence monitoring, and/or preselecting patients for PDGF-directed cancer therapies.
Midkine is a multifunctional peptide which, together with pleiotrophin, forms a structurally distinct family of heparin-binding growth factors. The paper presents the structure of midkine together with its amino-acid sequence and the functions of its domains as well as structural differences between the physiological forms of this peptide and those found in tumors. The localization of the midkine gene and its tissue expression both in embryonic life and in mature organisms is described. The available information on midkine receptors is discussed in detail. Most often they seem to be proteoglycans containing heparan sulfate and chondroitin sulfate, which can also be a part of the multimolecular receptor complexes binding midkine. The variety of midkine receptors is probably responsible for the diverse biological activity of this peptide. The paper presents up-to-date views on the biological activity of midkine both at the cellular (mitogenic properties, participation in apoptosis, and cellular migration, adhesion, morphological differentiation, and chemokine synthesis stimulation) and tissue levels (participation in organogenesis, tissue regeneration and protection and in the formation and degradation of extracellular matrix).
Lymph node metastasis (LNM) is a key factor for selection of treatment method and patients' prognosis in oesophageal squamous cell carcinoma (ESCC). However, no biomarkers able to support the clinical detection of LNM have been reported. Recently, vascular endothelial growth factor C (VEGF-C) was found to be a more accurate marker of LNM in lung cancer than computed tomography. Midkine is a multifunctional cytokine involved in cancer development. We investigated circulating midkine levels in ESCC patients (n=73) compared with those in healthy subjects (n=42) with double-antibody-sandwich indirect enzyme-linked immunosorbent assay (DASI-ELISA). We found that midkine was elevated in ESCC and involved in metastatic disease. Serum midkine (sMK) was a good marker of LNM, evaluated both clinically and pathologically, as revealed by ROC analysis. It also correlated with serum levels of VEGF-C. The increase of sMK was related to cancer cells, although a weak correlation was observed between sMK and platelet and leucocyte counts.
Despite the acknowledged contribution of eosinophils to the disease pathogenesis, available data on cytokines closely related to the peripheral eosinophils in inflammatory bowel disease (IBD) are scattered. We assessed the concentrations of eosinophil-associated cytokines and growth factors in the group of 277 individuals (101 patients with Crohn’s disease (CD), 77 with ulcerative colitis (UC), 16 with irritable bowel syndrome (IBS), and 83 healthy controls) and referred to IBD activity and the levels of hsCRP. As compared to IBS patients or healthy controls, patients with CD had significantly higher levels of IL5, IL8, IL12(p70), GM-CSF, and TNF α and patients with UC, the levels of eotaxin, IL4, IL5, IL8, IL12(p70), IL13, GM-CSF, and TNF α were also higher. As compared to CD patients, patients with UC had significantly higher levels of eotaxin, IL4, IL5, IL8, and IL1. In turn, the concentrations of hsCRP were significantly higher in CD than UC. Except for IL13, all cytokines and hsCRP positively correlated with CDAI. In UC, a positive correlation with MDAI was observed for hsCRP, GM-CSF, IL12(p70), and IFN γ and a negative one for IL8. The concentrations of hsCRP, GM-CSF, IFN γ , IL12(p70), and RANTES were higher in UC patients with active than inactive disease whereas those of IL8 and TNF α were significantly lower. Eotaxin, determined individually or in a panel with IFN γ and hsCRP, showed fair accuracy in differentiating CD from UC. If confirmed on a larger representation of IBS patients, IL8 might support differential diagnosis of organic and functional conditions of the bowel. GM-CSF, in turn, demonstrated to be an excellent indicator of bowel inflammation and may be taken into consideration as a noninvasive marker of mucosal healing. In summary, eosinophil-associated cytokines are elevated in IBD, more pronouncedly in UC, and may support the differential diagnosis of IBD and aid in monitoring of mucosal healing.
