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  • Residing in West Germany also decreased BIS persistence In J


    Residing in West Germany also decreased BIS persistence. In 2015, Jacob et al. demonstrated in 4,915 BC women that the treatment discontinuation rate is higher in West Germany than in East Germany [1]. Finally, our study returned one outcome that requires careful discussion: we found that private health insurance increased the risk of treatment discontinuation. This finding may cause confusion since women with private health insurance coverage are usually wealthier than those with statutory insurance coverage. Although patients who subscribe to a private health insurance plan may benefit from better medical treatment and management, one must consider the fact that these patients may display risk factors for therapy disruption not present or less present in other patients.
    Introduction Osteosarcoma (OS) is the most common type of primary bone cancer that mainly affects younger populations [1,2]. Current therapies combining surgery with chemotherapy (doxorubicin and cisplatin with or without methotrexate) yield 60–70% of the 5-year survival rate. However, the effective cure for patients with metastatic or relapsed osteosarcoma is still challenging [3]. Therefore, improvement of the existing therapies and exploitation of other approaches are highly anticipated. Radiotherapy is an alternative combinatory therapy for OS. The incorporation of radiotherapy significantly improved the efficiency of chemotherapy by certain anticancer drugs (e.g., ifosfamide, cisplatin, HDMTX, etc.) [4], which even led to a long-term remission in some patients [5]. Locally complete cure could also be observed in unresectable or partially resected cases by radiotherapy when applied at high intensity [6]. Nevertheless, OS is generally considered radioresistant with poorly understood mechanism [7]. In this study, we found HIF-1α was overexpressed in human OS tissues. HIF Bindarit are often indicators of hypoxia which is common in solid tumors like OS where blood supply in the microenvironment is usually limited [8–11]. In cancer stem cells, HIF proteins promote tumor aggressiveness and confer resistance to certain therapies including irradiation [12–15]. The mechanism that tumor with hypoxia has reduced sensitive to radiotherapy is well studied [16]. It is known that irradiation generates free radicals on DNA. At the normal condition, these radicals can be fixed by oxygen (O2) to generate DNA-damaging ROS products which will initiate cellular death. However, this death-inducing effect is compromised when the oxygen availability is low in hypoxic cells and ROS production is therefore limited [17]. Here, we found an additional mechanism that involves autophagy in the mechanism of OS radioresistance, which is independent of oxygen at the time during irradiation. Autophagy is a process in which subcellular organelles or complex of proteins are sequestrated by intracellular membranes and then fused with lysosomes for degradation. This process is an important to eliminate damaged cellular components and maintain cellular survival [18]. Autophagy has been evidenced to be involved in cancer [19–21], and recent studies suggest its contribution to radioresistance in various tumors. Lomonaco et al. have found the induction of autophagy contributes to the radioresistance of glioma stem cells [22]. The Rodemann group also reported that autophagy also caused resistance to ionizing radiation in breast cancer cell lines [23]. The similar phenomenon was additionally evidenced in pancreatic cancer cells [24]. Another study also thoroughly support the role of autophagy in mediating radioresistance [25].
    Materials and methods
    Discussion Insights from studies on cancer stem cells which often demonstrate resistance to irradiation include: 1) prolonged S-phase in cell cycle or more population of cells in this phase as mitotic cells are more sensitive to irradiation; 2) increased DNA repair activity; 3) enhanced ROS scavenging capacity and upregulated HIF-1α; and 4) rescuing cues from stromal environment [12]. Here it is very clear that accelerated ROS clearance and activated hypoxic response are among common mechanisms for radioresistance. We have found in this study that both of these are present in the human osteosarcoma, although other mechanism mentioned here might be existent as well.