Cancer immunotherapy uses the immune system and its components to mount an anti-tumor response. During the last decade, it has evolved from a promising therapy option to a robust clinical reality. To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure.
The thymus is a central lymphoid organ with crucial role in generating T cells and maintaining homeostasis of the immune system. More than 30 peptides, initially referred to as "thymic hormones," are produced by this gland. Although the majority of them have not been proven to be thymus-specific, thymic peptides comprise an effective group of regulators, mediating important immune functions. Thymosin fraction five (TFV) was the first thymic extract shown to stimulate lymphocyte proliferation and differentiation. Subsequent fractionation of TFV led to the isolation and characterization of a series of immunoactive peptides/polypeptides, members of the thymosin family. Extensive research on prothymosin α (proTα) and thymosin α1 (Tα1) showed that they are of clinical significance and potential medical use. They may serve as molecular markers for cancer prognosis and/or as therapeutic agents for treating immunodeficiencies, autoimmune diseases and malignancies. Although the molecular mechanisms underlying their effect are yet not fully elucidated, proTα and Tα1 could be considered as candidates for cancer immunotherapy. In this review, we will focus in principle on the eventual clinical utility of proTα, both as a tumor biomarker and in triggering anticancer immune responses. Considering the experience acquired via the use of Tα1 to treat cancer patients, we will also discuss potential approaches for the future introduction of proTα into the clinical setting.
Natural products are characterized by extreme structural diversity and thus they offer a unique source for the identification of novel anti-tumor agents. Herein, we report that the herbal substance acteoside being isolated by advanced phytochemical methods from Lippia citriodora leaves showed enhanced cytotoxicity against metastatic tumor cells; acted in synergy with various cytotoxic agents and it sensitized chemoresistant cancer cells. Acteoside was not toxic in physiological cellular contexts, while it increased oxidative load, affected the activity of proteostatic modules and suppressed matrix metalloproteinases in tumor cell lines. Intraperitoneal or oral (via drinking water) administration of acteoside in a melanoma mouse model upregulated antioxidant responses in the tumors; yet, only intraperitoneal delivery suppressed tumor growth and induced anti-tumor-reactive immune responses. Mass-spectrometry identification/quantitation analyses revealed that intraperitoneal delivery of acteoside resulted in significantly higher, vs. oral administration, concentration of the compound in the plasma and tumors of treated mice, suggesting that its in vivo anti-tumor effect depends on the route of administration and the achieved concentration in the tumor. Finally, molecular modeling studies and enzymatic activity assays showed that acteoside inhibits protein kinase C. Conclusively, acteoside holds promise as a chemical scaffold for the development of novel anti-tumor agents.
Abstract. Background/Aim: Certain microRNAs (miRs) present in human plasma are candidate biomarkers for cardiovascular diseases, including acute myocardial infarction (AMI). We examined the expression of two cardiac-specific miRs (miR-208b and miR-499) MicroRNAs (miRs) are evolutionary small endogenous, noncoding, single-stranded RNAs involved in the regulation of gene expression at the post-transcriptional level (1). They possess an important role in multiple biological processes by binding to their target mRNAs and altering the protein expression of their candidate targets (2). Circulating miRs detected in serum or plasma, are actively secreted in macrovesicles or exosomes from different cell types (3), including cardiomyocytes. Elevated mRNA expression levels have been involved in numerous human pathologies including cardiovascular diseases (4).Acute myocardial infarction (AMI) is the acute necrosis of myocardial tissue due to persistent and severe ischemia, and remains a leading cause of morbidity and mortality worldwide (5). Accurate and rapid diagnosis is crucial for the clinical management and prognosis of AMI (6). Thus, exploration of new potential biomarkers that will contribute in this direction is particularly important. Although the circulating levels of cardiac troponin proteins are currently regarded as the most prominent biomarkers for the diagnosis of AMI, measurable amounts of troponins are not usually released from damaged myocardium earlier than 4-8 h after the onset of symptoms (6, 7). In contrast, the levels of circulating plasma miRs can be measured rapidly using realtime PCR, offering two main advantages over standard antibody-based assays: increased sensitivity and specificity. Several studies have already considered circulating cardiacspecific or -enriched miRs as new biomarkers for the early diagnosis of .In fact, the vast majority of these studies have been performed in Asian populations, while limited studies from European populations are also available (12). Consequently, better validation through larger studies is required for the establishment of miRs as biomarkers in clinical practice. Based on the elegant study of Huang et al. (13) who showed that miRNA expression levels exhibit population differences, and the recorded dysregulation of two specific myocardialderived miRNAs in AMI patients (14, 15), we decided to further investigate their expression in a Caucasian population. Specifically, the purpose of this study was to 313
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