Ability of electromagnetic fields (EMF) to stimulate cell proliferation and differentiation has attracted the attention of many laboratories specialized in regenerative medicine over the past number of decades. Recent studies have shed light on bio-effects induced by the EMF and how they might be harnessed to help control tissue regeneration and wound healing. Number of recent reports suggests that EMF has a positive impact at different stages of healing. Processes impacted by EMF include, but are not limited to, cell migration and proliferation, expression of growth factors, nitric oxide signalling, cytokine modulation, and more. These effects have been detected even during application of low frequencies (range: 30-300 kHz) and extremely low frequencies (range: 3-30 Hz). In this regard, special emphasis of this review is the applications of extremely low-frequency EMFs due to their bio-safety and therapeutic efficacy. The article also discusses combinatorial effect of EMF and mesenchymal stem cells for treatment of neurodegenerative diseases and bone tissue engineering. In addition, we discuss future perspectives of application of EMF for tissue engineering and use of metal nanoparticles activated by EMF for drug delivery and wound dressing. Original language EnglishPages (from-to) [485][486][487][488][489][490][491][492][493]

The progression of colorectal cancer is commonly characterized by accumulation of genetic or epigenetic abnormalities, altering regulation of gene expression as well as normal protein structures and functions. Nonetheless, there are some questions that remain to be elucidated, such as the origin of cancer cells and populations of cells initiating and propagating tumor development. Currently, there are two rival theories describing the process of carcinogenesis. One is the stochastic model, arguing that any cell is capable of initiating and triggering the development of cancer. Meanwhile, the cancer stem cell model hypothesizes that only a small fraction of stem cells possesses cancerpromoting properties. Typically, colorectal cancer stem cells (CSCs) share the same molecular signaling profiles with normal stem cells or embryonic stem cells, such as Wnt, Notch, TGF-β, and Hedgehog. Nevertheless, CSCs differ from normal stem cells and the bulk of tumor cells in their tumorigenic potential and susceptibility to chemotherapeutic drugs. This may be a possible explanation of the high percentage of cancer recurrence in patients who underwent chemotherapeutic treatment and surgery. This review article focuses on the colorectal cancer stem cell biomarkers and the role of upregulated signaling pathways implicated in the initiation and progression of colorectal cancer.

The main aim of oncologists worldwide is to understand and then intervene in the primary tumor initiation and propagation mechanisms. This is essential to allow targeted elimination of cancer cells without altering normal mitotic cells. Currently, there are two main rival theories describing the process of tumorigenesis. According to the Stochastic Model, potentially any cell, once defunct, is capable of initiating carcinogenesis. Alternatively the Cancer Stem Cell (CSC) Model posits that only a small fraction of undifferentiated tumor cells are capable of triggering carcinogenesis. Like healthy stem cells, CSCs are also characterized by a capacity for self-renewal and the ability to generate differentiated progeny, possibly mediating treatment resistance, thus leading to tumor recurrence and metastasis. Moreover, molecular signaling profiles are similar between CSCs and normal stem cells, including Wnt, Notch and Hedgehog pathways. Therefore, development of novel chemotherapeutic agents and proteins (e.g., enzymes and antibodies) specifically targeting CSCs are attractive pharmaceutical candidates. This article describes small molecule inhibitors of stem cell pathways Wnt, Notch and Hedgehog, and their recent chemotherapy clinical trials. Original language EnglishPages (from-to) 909-918