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.
The first DBPC SCIT-DRF with a mixture of recombinant Phleum allergens (Phl p 1, 2, 5a, 5b, 6) in patients with rhinoconjunctivitis plus/minus asthma showed no major side effects in very high doses up to 120 μg.
Opinion StatementImmunotherapy for type I allergies is well established and is regarded to be the most efficient treatment option besides allergen avoidance. As of today, different forms of allergen preparations are used in this regard, as well as different routes of application. Virus-like particles (VLPs) represent a potent vaccine platform with proven immunogenicity and clinical efficacy. The addition of toll-like receptor ligands and/or depot-forming adjuvants further enhances activation of innate as well as adaptive immune responses. CpG motifs represent intensively investigated and potent direct stimulators of plasmacytoid dendritic cells and B cells, while T cell responses are enhanced indirectly through increased antigen presentation and cytokine release. This article will focus on the function of VLPs loaded with DNA rich in nonmethylated CG motifs (CpGs) and the clinical experience gained in the treatment of allergic rhinitis, demonstrating clinical efficacy also if administered without allergens. Several published studies have demonstrated a beneficial impact on allergic symptoms by treatment with CpG-loaded VLPs. Subcutaneous injection of VLPs loaded with CpGs was tested with or without the adjuvant alum in the presence or absence of an allergen. The results encourage further investigation of VLPs and CpG motifs in immunotherapy, either as a stand-alone product or as adjuvants for allergen-specific immunotherapy.
Objective Growing interest in measuring the cochlear duct length (CDL) has emerged, since it can influence the selection of cochlear implant electrodes. Currently the measurements are performed with ionized radiation imaging. Only a few studies have explored CDL measurements in magnetic resonance imaging (MRI). Therefore, the presented study aims to fill this gap by estimating CDL in MRI and comparing it with multislice computed tomography (CT). Study Design Retrospective data analyses of 42 cochleae. Setting Tertiary care medical center. Methods Diameter (A value) and width (B value) of the cochlea were measured in HOROS software. The CDL and the 2-turn length were determined by the elliptic circular approximation (ECA). In addition, the CDL, the 2-turn length, and the angular length were determined via HOROS software by the multiplanar reconstruction (MPR) method. Results CDL values were significantly shorter in MRI by MPR ( d = 1.38 mm, P < .001) but not by ECA. Similar 2-turn length measurements were significantly lower in MRI by MPR ( d = 1.67 mm) and ECA ( d = 1.19 mm, both P < .001). In contrast, angular length was significantly higher in MRI ( d = 26.79°, P < .001). When the values were set in relation to the frequencies of the cochlea, no clinically relevant differences were estimated (58 Hz at 28-mm CDL). Conclusion In the presented study, CDL was investigated in CT and MRI by using different approaches. Since no clinically relevant differences were found, diagnostics with radiation may be omitted prior to cochlear implantation; thus, a concept of radiation-free cochlear implantation could be established.
The inferior colliculus (IC) is a nucleus of the auditory pathway and its fourth relay station. It integrates afferent information from the superior olivary complex and the cochlear nucleus. To date, no causal therapeutic options are known for damaged neuronal structures in this area. Regenerative medicine offers a potential approach to causally treating hearing impairment. After neural stem cells had been identified in certain areas of the auditory pathway, the question arouses, whether the IC also has a neurogenic potential. Cells from the IC of postnatal day 6 rats were extracted and cultured as neurospheres. Cells in the neurospheres showed mitotic activity and positive stain of neural stem cell markers (Nestin, DCX, Atoh1, and Sox-2). In addition, single cells were differentiated into neuronal and glial cells shown by the markers β-III-tubulin, GFAP, and MBP. In summary, basic stem cell criteria could be detected and characterized in cells isolated from the IC of the rat. These findings will lead to a better understanding of the development of the auditory pathway and may also be relevant for identifying causal therapeutic approaches in the future.
Hypothesis:
Flat-panel volume computed tomography (fpVCT) and secondary reconstruction allow for more accurate measurements of two-turn length (2TL), cochlear duct length (CDL), and angular length (AL).
Background:
Cochlear geometry is a controversially debated topic. In the meantime, there are many different studies partly reporting highly divergent values. Our aim is to discuss the differences and to propose a radiological possibility to improve cochlear measurements using 3D-curved multiplanar reconstruction and fpVCT.
Methods:
Performing different image modalities and settings, we tried to find a clinically usable option that allows for a high degree of accuracy. Therefore, we tested them against reference values of high-definition micro-computed tomography.
Results:
Comparison of 99 μm slice thickness secondary reconstruction of fpVCT and reference showed no significant differences for 2TL and CDL (p ≥ 0.05). Accordingly, ICC (intraclass correlation) values were excellent (ICC ≥ 0.75; lower limit of confidence interval [CI] ≥ 0.75; Cronbach's alpha [α] ≥ 0.9). Evaluating AL, there was a significant difference (difference: −17.27°; p = 0.002). The lower limit of the CI of the ICC was unacceptable (ICC = 0.944; lower limit of CI = 0.248; α = 0.990). Regarding the Bland-Altman plots, there were no clinically unacceptable errors, but a systematic underestimation of AL.
Conclusion:
Secondary reconstruction is a suitable tool for producing reliable data that allow the accurate measurement of 2TL and CDL. The option of generating these reconstructions from raw data limits the need for higher radiation doses. Nevertheless, there is an underestimation of AL using secondary reconstructions.
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