According to literature data, potentially premalignant oral lesions are the basis of over 85% of cell carcinomas. Despite multiple advances achieved during the last few decades in the diagnosis and treatment of oral squamous cell carcinomas, there has not been a significant change in the prognosis and 5-year survival rate. The prevention of malignant transformation of these tumors by diagnosis and targeted treatment would be the ideal scenario. These potentially premalignant oral lesions represent an important subject for either the clinical or the research field, due to the higher malignant transformation observed in the last few years at different ages. To date, histopathological examination based on TNM criteria is considered the ‘golden standard’. However, this type of examination has its limitation due to staining procedures and photonic microscope examination. Identification of cellular and molecular markers specific to these oral lesions with potentially malignant transformation could lead to early detection, accurate diagnosis, prevention of the development of oral squamous cell carcinoma (OSCC) and facilitate a targeted therapeutic approach. In this review, we focused on a series of molecules that are implicated in the malignant transformation of these lesions and considered potential biomarkers.
Mitocurcumin (a triphenylphosphonium curcumin derivative) was previously reported as a selective antitumoral compound on different cellular lines, as well as a potent bactericidal candidate. In this study, the same compound showed strong antimicrobial efficacy against different strains of methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration was identical for all tested strains (four strains of MRSA and one strain of methicillin-sensitive Staphylococcus aureus), suggesting a new mechanism of action compared with usual antibacterial agents. All tested strains showed a significant sensitivity in the low micromolar range for the curcumin-triphenylphosphonium derivative. This susceptibility was modulated by the menadione/glutathione addition (the addition of glutathione resulted in a significant increase in minimal inhibitory concentration from 1.95 to 3.9 uM, whereas adding menadione resulted in a decrease of 0.49 uM). The fluorescence microscopy showed a better intrabacterial accumulation for the new curcumin-triphenylphosphonium derivative compared with simple curcumin. The MitoTracker staining showed an accumulation of reactive oxygen species (ROS) for a S. pombe superoxide dismutase deleted model. All results suggest a new mechanism of action which is not influenced by the acquired resistance of MRSA. The most plausible mechanism is reactive oxygen species (ROS) overproduction after a massive intracellular accumulation of the curcumin-triphenylphosphonium derivative.
Cyclodextrins (CDs), a group of oligosaccharides formed by glucose units bound togetherin a ring, showed a promising ability to form supramolecular complexes with drug molecules and improved theirphysicochemical properties without any molecular modifications. On the other hand, a large number of synthetic curcumin derivatives showed promising anticancer results on malignant cell cultures in recent years. This study presents the advantages and limitations of CDs (potential enhancers of solubility and stability) when are used together with a series of curcumin complexes. All the CD-curcumin complex mixtures were tested as potential anticancer agents on a human osteosarcoma cell culture. A variant of beta-cyclodextrin (monochlorotriazinyl-β-cyclodextrin sodium salt) was found to exhibit the best results in terms of solubility and cytotoxicity enhancements. The results(expressed as inhibitory concentrations for 50 % cell viability - IC50) showed significant improvements for manganese and cooper curcumin complexes and had no effects for boron and thorium complexes.
The results of the recent years researches support the need for personalized therapeutic of cancer by completing the clinical, imagistic and histopathological diagnosis with molecular studies to identify new useful biomarkers for diagnosis, prognosis and tumor progression. Maspin is a non-inhibitory serine protease having a proapoptotic activity, suppressor of tumor invasion, metastasis and angiogenesis. Ezrin is a member of Ezrin/Radixin/Moesin (ERM) family, involved in cellular adhesion mechanisms, motility and invasiveness of tumor cells. In colorectal tumors, there is a heterogeneity of research results regarding the clinical significance of the maspin due to a possible partnership with other molecules with which it interacts through the same signaling pathways. Our study investigated the two molecule�s immunoreactivity (IR) in 92 colorectal tumors highlighting an inverse correlation between ezrin�s and maspin�s expression, suggesting the fact that ezrin�s overexpression could influence maspin�s tumoral suppressor role. Furthermore there was observed a difference of the molecules IR within the same tumoral stage, suggesting their utility regarding the treatment protocol of these tumors.
Introduction. The cardiac allograft rejections from the post-transplant period are attributable to the acute cellular rejection monitored by multiple endomyocardial biopsies. Compared to this, humoral rejection remains a matter of debate, with multiple therapeutic strategies, poor prognosis, and persisting uncertainty about diagnostic criteria. Acute allograft rejection is associated with significant modifications of the extracellular matrix compartment mainly regulated by matrix metalloproteinases (MMPs). In this context, the aim of this study was to evaluate the expression of MMP-2 and -9 and CD31, CD68 (endothelial and histiocytic markers) and the correlations between them using immunohistochemistry, in patients with cardiac allografts. Materials and methods. Tissue fragments were obtained by endomyocardial biopsy from 5 patients with allograft heart transplant, 2 in the medium post-transplant phase and 2 in late phase. After identifying and characterizing the morphological context the probes were processed by standard immunohistochemical technique using anti-MMP-2 and anti-MMP-9 antibodies (Santa Cruz Biotechnology, Inc.) and anti-CD31, anti-CD68 antibodies (Sigma). The samples were examined using the Olympus BX40 microscope with an Olympus E330 camera attached. Results and discussions. Sample examination revealed in all 4 cases the lack of IR (-) for CD31 and weak IR (+) for CD68 compared to MMPs, where we found moderate IR (++) for MMP-9 and weak IR (+) for MMP-2. These aspects complets the histological lesional aspects of these cases, indicating the lack of acute rejection. In conclusion, CD31 and CD68 IR correlated with MMPs IR (especially MMP-9) appear to represent predictive markers for cardiac allograft rejection and require further studies.
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