“Introduction Pancreatic cancer is a devastating disease t


“Introduction Pancreatic check details cancer is a devastating disease that is generally detected at a late stage. Surgical resection is the only potentially curative treatment; however, only 10 to 20% of patients are candidates for curative surgical resection due to advanced diagnosis, poor patient condition and tumor location. The remaining patients have to seek alternative

therapies [1–3]. Even with resection, long term survival remains poor, with a median survival of 12 – 20 months. The survival rate of pancreatic cancer patients is so short, that treatment tends to be palliative. Recently, palliative surgery, endoscopic drainage, chemotherapy or brachytherapy alone or in combination have been used to elongate the survival and alleviate pain or jaundice symptoms [4–7]. Iodine-125 (125I) brachytherapy with either external beam radiation therapy (EBRT) or interstitial brachytherapy (IBT) improve local AZD1390 clinical trial control and increase survival [8–10]. However, EBRT requires high doses of irradiation for efficacy [8]. Moreover, the very radioresponsive organs surrounding the pancreas adversely affect the dose of radiation used to target

the tumor on radiation treatment [9]. Fractionated EBRT is only effective on cancer cells before metastasis occurs, and the efficiency of EBRT is usually impaired because, between irradiation treatments, tumor cells in the stationary phase enter the mitotic stage [8, 9]. As a result, IBT has been introduced as treatment for unresectable pancreatic cancers to maximize local dose and minimize irradiation of the surrounding normal tissue [10]. Recently, 125I seed implantation, an efficient Tideglusib cell line IBT technique, has attracted increasing attention because of its specific advantages: 1) effective irradiation dose applied in a single procedure; 2) reduced irradiation outside the target tumor; 3) elongating aminophylline the tumor killing over several weeks or months; 4) percutaneous implantation under the guidance of ultrasound or CT [11, 12]. Cancer irradiation therapy may keep

tumor cells in the sensitive resting period, resulting in tumor cell apoptosis, inducing epigenetic changes to reactivate silenced tumor suppressor genes, and damaging DNA to kill the cancer cells. However, the radiobiological effect of persistent and low-energy 125I irradiation, especially on epigenetic modifications and apoptosis are not fully understood. Cancer cell apoptosis is an indicator of response to cancer treatment. Aberrant DNA methylation in cancer cells is a critical epigenetic process involved in regulating gene expression. DNA hypermethylation is associated with tumor suppressor gene silencing and defects in cell cycle regulation, resulting in tumor development and progression [13, 14]. The DNA methyltransferases DNMT1, DNMT3a, and DNMT3b are the three main functional enzymes that are responsible for establishing and maintaining DNA methylation patterns in mammalian cells.

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