Human mesenchymal stem cells (hMSC) are frequently used in tissue engineering. Due to their strong tumor tropism, hMSC seem to be a promising vehicle for anticancer drugs. However, interactions between hMSC and cancer are ambiguous. Particularly the cytokines and growth factors seem to play an important role in cancer progression and metastasis. The present study evaluated the effects of hMSC on head and neck squamous cell carcinoma (HNSCC) cell lines (FaDu and HLaC78) in vitro. hMSC released several cytokines and growth factors. FaDu and HLaC78 showed a significant enhancement of cell proliferation after cultivation with hMSC-conditioned medium as compared to control. This proliferation improvement was inhibited by the addition of anti-IL-6. The western blot showed an activation of Erk1/2 in FaDu and HLaC78 by hMSC-conditioned medium. HNSCC cell lines expressed EGFR. The current study confirms the importance of cytokines secreted by hMSC in cancer biology. Especially IL-6 seems to play a key role in cancer progression. Thus, the use of hMSC as a carrier for cancer therapy must be discussed critically. Future studies should evaluate the possibility of generating genetically engineered hMSC with, for example, the absence of IL-6 secretion.
Zinc oxide nanoparticles (ZnO-NP) are widely spread in consumer products. Data about the toxicological characteristics of ZnO-NP is still under controversial discussion. The human skin is the most important organ concerning ZnO-NP exposure. Intact skin was demonstrated to be a sufficient barrier against NPs; however, defect skin may allow NP contact to proliferating cells. Within these cells, stem cells are the most important toxicological target for NPs. The aim of this study was to evaluate the genotoxic and cytotoxic effects of ZnO-NP at low-dose concentrations after long-term and repetitive exposure to human mesenchymal stem cells (hMSC). Cytotoxic effects of ZnO-NP were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Furthermore, genotoxicity was evaluated by the comet assay. For long-term observation over 6 weeks, transmission electron microscopy (TEM) was applied. The results of the study indicated cytotoxic effects of ZnO-NP beginning at high concentrations of 50 μg/mL and genotoxic effects in hMSC exposed to 1 and 10 μg/mL ZnO-NP. Repetitive exposure enhanced cyto- but not genotoxicity. Intracellular NP accumulation was observed up to 6 weeks. The results suggest cytotoxic and genotoxic potential of ZnO-NP. Even low doses of ZnO-NP may induce toxic effects as a result of repetitive exposure and long-term cellular accumulation. This data should be considered before using ZnO-NP on damaged skin.
The increasing usage of zinc oxide nanoparticles (ZnO-NPs) in industrial applications as well as in consumer products raises concern regarding their potential adverse effects to a greater extend. Numerous studies have demonstrated toxic properties of NPs, however there is still a lack of knowledge concerning the underlying mechanisms. This study was designed to systematically investigate cytotoxicity, apoptosis, cell cycle alterations, and genotoxicity induced by ZnO-NP. Moreover, it was an aim of the investigations to specify the diverse effects of nanoparticle exposure in malignant in comparison with non-malignant cells. Therefore, human head and neck squamous cell carcinoma-derived FaDu cells were incubated with 4-20 µg/ml of ZnO-NPs for 1-48 hr and tested for cell viability, cell cycle alterations, apoptosis and caspase-3 gene expression as a sensitive marker of molecular apoptotic processes with regard to time- and dose-dependent effects. Human mesenchymal bone marrow stem cells were used as non-malignant representatives to examine oxidative stress-related genotoxicity. Results showed a significant reduction in cell viability as well as dose- and time-dependent increase of apoptotic cells following nanoparticle treatment. Likewise, caspase-3 gene expression enhanced already before first apoptotic cells were detectable. It could be observed that doses that were cytotoxic in tumor cells did not reduce viability in stem cells. However, the same concentrations already induced significant DNA damage. The findings of the study suggest to keep a more critical eye on the use of nanoparticles as anti-cancer agents. Yet, additional in vivo studies are needed to assess safety concerns for consumers and patients. Environ. Mol. Mutagen. 59:247-259, 2018. © 2017 Wiley Periodicals, Inc.
Summary Adenotonsillectomies are commonly performed procedures and sleep‐disordered breathing is becoming increasingly important as an indication for surgery. Because of the higher risks in patients with obstructive sleep apnoea, the required level of postoperative care for these patients is currently under discussion, and better identification of patients at risk may reduce unnecessary postoperative monitoring. To evaluate the influence of obstructive sleep apnoea, and other risk factors, on peri‐operative complications in children requiring adenotonsillectomy, we performed a retrospective case‐control study that included 1995 patients treated between January 2009 and June 2017. In our analysis, young age (OR 3.8, 95%CI 2.1–7.1), low body weight (OR 2.6, 95%CI 1.5–4.4), obstructive sleep apnoea (OR 2.4, 95%CI 1.5–3.8), pre‐existing craniofacial or syndromal disorders (OR 2.3, 95%CI 1.4–3.8) and adenotonsillectomy, compared with adenoidectomy alone, (OR 7.9, 95%CI 4.7–13.1) were identified as risk factors for complications during or after surgery, p < 0.001. All 13 patients suffering from complications more than 3 h postoperatively had obstructive sleep apnoea plus at least one more of these risk factors. Patients at risk of postoperative complications can therefore be identified by several criteria pre‐operatively, and should be monitored postoperatively using pulse oximetry overnight. For all other patients, postoperative observation on a surgical ward without extra monitoring is sufficient. Admission to paediatric intensive care should be reserved for patients suffering serious intra‐operative complications.
Laser haemorrhoidoplasty (LHP) with the 1470 nm diode laser in minimally invasive surgery for advanced haemorrhoid disease has been studied with respect to clinical variables, such as pain and complications, and intraoperative characteristics such as mucopexia, number of treated knots and energy consumed per patient. The study also included patient satisfaction, symptom relevance and cost effectiveness. Between November 2010 and November 2016, 497 patients (age 55 ± 14 years) were submitted to laser haemorrhoidoplasty with a 1470 nm diode laser in the centre for minimally invasive proctology in Siegen District Hospital. All operated patients were included in the study. Perioperative clinical and technical data up to 6 weeks and follow-up data up to 6 months were analysed prospectively. The mean duration of operation was 14 min (± 5.2). A mean of 2.7 knots of 2.7 size were treated per patient. The mean postoperative pain was 2.5/10 (VAS). Long-term symptom relevance was 86%, and patient satisfaction 91%. Complications occurred in 49 patients (9.9%): bleeding 1.8%, infection 1%, urine retention 1.8%, oedema/thrombosis/prolapse 6.6%. 8.8% of patients suffered a relapse within 6 months. There were significant differences in pain on the day of the operation, and the parameters mucopexia, 3 treated segments and energy level > 500 J (p < 0.05). Complications were more common when mucopexia was performed, with 3 treated knots and energy consumed per patient > 500 J. The only significant difference was for energy level > 500 J (p < 0.05). LHP is a safe, low pain and minimally invasive surgical procedure with long-term good patient acceptance and satisfaction and is suited for routine work. The energy applied should be reduced to a minimum. Complication rates are largely comparable with those of other minimally invasive conventional methods. Additional prospective studies must be performed, particularly in comparison to the Parks method, which gives similar functional results. With circular confluent findings, LHP cannot replace stapler hemorrhoidopexia.
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