The genus Helleborus comprises 22 species, which are allocated to six Helleborus sections. Helleborus species show differences with regard to leaf and flower morphology, scent, and sensitivity to ...different pests and diseases. Breeding programs aiming at these traits require the inclusion of a broader spectrum of Helleborus species in addition to the most popular species H. niger (Christmas Rose) and H. × hybridus (Lenten Rose), thus interspecific hybridisations need to be performed. Pollen viability was estimated for nine species by staining with thiazolyl blue (MTT) and varied between 67 and 99% for fresh pollen and between 74 and 99% for pollen dried for 24 h. Crossing barriers had previously been localized in Helleborus species as predominantly post-zygotic. Therefore, embryo rescue techniques via ovule culture were established to overcome these barriers. Ovules were isolated from the maternal plants five to seven weeks after pollination and then cultured in vitro. Overall, from 661 crosses involving 13 Helleborus species, 40,885 ovules were obtained. In a combination with parents of low genetic distances between the parental species, up to 26.08% of these ovules produced hybrid shoots, whereas in intersectional crosses this was the case in only 0.17 to 0.85% of the ovules. In total, 217 hybrid offspring were verified by flow cytometry and molecular marker analysis (random amplified polymorphic DNAs), whereof 16 were derived from parental species belonging to different Helleborus sections. Hybrid plantlets of some cross combinations were transferred to the greenhouse and expressed intermediate leaf and flower morphology when compared to the parental species.
Oligodeoxynucleotides containing unmethylated CpG dinucleotides induce innate and adaptive immunity through Toll-like receptor 9 (TLR9). In the present study, we have examined the ability of a novel ...agonist of TLR9, called immunomodulatory oligonucleotide (IMO), to enhance effects of a HER-2/neu plasmid DNA electroporation/adenovirus (DNA-EP/Ad) vaccine.
BALB/NeuT mice were treated with DNA-EP vaccine alone, IMO alone, or the combination of two agents starting at week 13, when all mice showed mammary neoplasia. Tumor growth and survival were documented. Antibody and CD8+ T-cell responses were determined. Peptide microarray analysis of sera was carried out to identify immunoreactive epitopes. Additionally, microCT and microPET imaging was carried out in an advanced-stage tumor model starting treatment at week 17 in BALB/NeuT mice.
The combination of DNA-EP and IMO resulted in significant tumor regression or delay to tumor progression. 2-Deoxy-2-18Ffluoro-D-glucose microPET and microCT imaging of mice showed reduced tumor size in the DNA-EP/IMO combination treatment group. Mice treated with the combination produced greater antibody titers with IgG2a isotype switch and antibody-dependent cellular cytotoxicity activity than did mice treated with DNA-EP vaccine. An immunogenic B-cell linear epitope, r70, within the HER-2 dimerization domain was identified through microarray analysis. Heterologous DNA-EP/Ad vaccination combined with IMO increased mice survival.
The combination of HER-2/neu genetic vaccine and novel agonist of TLR9 had potent antitumor activity associated with antibody isotype switch and antibody-dependent cellular cytotoxicity activities. These results support possible clinical trials of the combination of DNA-EP/Ad-based cancer vaccines and IMO.
The HIT (Heidelberg Ion Beam Therapy Center) is the first hospital-based treatment facility in Europe where patients can be irradiated with protons and carbon ions. Since the commissioning starting ...in 2006 two 14.5 GHz electron cyclotron resonance ion sources are routinely used to produce a variety of ion beams from protons up to oxygen. In the future a helium beam for regular patient treatment is requested, therefore a third ion source (Supernanogan source from PANTECHNIK S.A.) will be integrated. This third ECR source with a newly designed extraction system and a spectrometer line is installed at a test bench at HIT to commission and validate this section. Measurements with different extraction system setups will be presented to show the improvement of beam quality for helium, proton, and carbon beams. An outlook to the possible integration scheme of the new ion source into the production facility will be discussed.
Magnetic resonance (MR) image guidance has demonstrated significant potential in the field of interventional radiology in several applications. This article covers the main points of MR-guided ...hepatic tumor ablation as a representative of MR-guided procedures. Patient selection and appropriate equipment utilization are essential for successful MR-guided tumor ablation. Intra-procedural planning imaging enables the visualization of the tumor and surrounding anatomical structures in most cases without the application of a contrast agent, ensuring optimal planning of the applicator tract. MRI enables real-time, multiplanar imaging, thus simultaneous observation of the applicator and target tumor is possible during targeting with adaptable slice angulations in case of challenging tumor positions. Typical ablation zone appearance during therapy monitoring with MRI enables safe assessment of the therapy result, resulting in a high primary efficacy rate. Recent advancements in ablation probes have shortened treatment times, while technical strategies address applicator visibility issues. MR-imaging immediately after the procedure is used to rule out complications and to assess technical success. Especially in smaller neoplasms, MRI-guided liver ablation demonstrates positive outcomes in terms of technical success rates, as well as promising survival and recurrence rates. Additionally, percutaneous biopsy under MR guidance offers an alternative to classic guidance modalities, providing high soft tissue contrast and thereby increasing the reliability of lesion detection, particularly in cases involving smaller lesions. Despite these advantages, the use of MR guidance in clinical routine is still limited to few indications and centers, due to by high costs, extended duration, and the need for specialized expertise. In conclusion, MRI-guided interventions could benefit from ongoing advancements in hardware, software, and devices. Such progress has the potential to expand diagnostic and treatment options in the field of interventional radiology.
Two genetically engineered, conditional mouse models of lung tumor formation, K-rasLSL-G12D and K-rasLSL-G12D/p53LSL-R270H, are commonly used to model human lung cancer. Developed by Tyler Jacks and ...colleagues, these models have been invaluable to study in vivo lung cancer initiation and progression in a genetically and physiologically relevant context. However, heterogeneity, multiplicity and complexity of tumor formation in these models make it challenging to monitor tumor growth in vivo and have limited the application of these models in oncology drug discovery. Here, we describe a novel analytical method to quantitatively measure total lung tumor burden in live animals using micro-computed tomography imaging. Applying this methodology, we studied the kinetics of tumor development and response to targeted therapy in vivo in K-ras and K-ras/p53 mice. Consistent with previous reports, lung tumors in both models developed in a time- and dose (Cre recombinase)-dependent manner. Furthermore, the compound K-rasLSL-G12D/p53LSL-R270H mice developed tumors faster and more robustly than mice harboring a single K-rasLSL-G12D oncogene, as expected. Erlotinib, a small molecule inhibitor of the epidermal growth factor receptor, significantly inhibited tumor growth in K-rasLSL-G12D/p53LSL-R270H mice. These results demonstrate that this novel imaging technique can be used to monitor both tumor progression and response to treatment and therefore supports a broader application of these genetically engineered mouse models in oncology drug discovery and development.
To evaluate the effects of radiation dose reduction on diagnostic accuracy and image quality of pulmonary angiography CT (CTPA) in adults with suspected pulmonary embolism (PE).
52 consecutive ...patients received CTPA for suspected PE. Realistic low-Dose CT simulations were generated using an offline software (ReconCT, Siemens Healthineers, Forchheim, Germany), as either filter back projections (FBP) or iterative reconstruction as ADMIRE (strength 3 or 5) with 25 %, 50 % and 75 % of the original dose. To assess image quality (overall image quality, noise, artifacts, and sharpness) and diagnostic confidence, a five-point scale was used. Patient-based and segment-based diagnostic accuracy was calculated for Low-dose computed tomography (LDCT)-reconstruction with original dose CTPA as a standard of reference. Furthermore, effective radiation doses were calculated using a commercially available dose management platform (Radimetrics, Bayer HealthCare, Leverkusen, Germany).
Among 52 patients, a total of 15 patients (28.8 %) had acute pulmonary artery embolism. The median dose-length product and effective dose for all 52 scans were 291.1 ± 210.1 mGy⋅cm and 5.8 ± 3.4 mSv. Overall subjective image quality was highest for ADMIRE 5 with 75 % and lowest for FBP with 25 % of the original dose (median interquartile range:5 5 vs. 3 2–3, p < 0.001. Patient-based diagnostic accuracy was perfect for all iteratively reconstructed data sets (ADMIRE 3 and 5) (sensitivity: 100 %, negative predictive value NPV: 100 %). LDCT data sets with FBP had perfect diagnostic accuracy at 50 % and 75 % of the original dose, which however decreased at 25 % of the original dose (sensitivity: 93 %; NPV: 97 %). Segment-based diagnostic accuracy was high for ADMIRE 3 and 5 down to 25 % dose reduction (sensitivity: 90.4 % specificity: 99.5 %) and lowest for FBP with 25 % dose reduction (sensitivity: 84.6 %, specificity: 98.9 %). Inter-class correlation regarding the detection of PE was almost perfect at all doses and recons (ICC: 96.1−1.0). Thus, accurate diagnosis for PE was possible for ADMIRE 3 and 5 datasets with 25 % of the original dose (1.45 mSv) and for FBP with 50 % of the original dose (2.9 mSv).
Our findings indicate that radiation dose reduction down to 25 % (1.45 mSv) of the original data via iterative reconstruction algorithms on a 3rd generation Dual Source CT (DSCT) scanner maintained the diagnostic accuracy and image quality for the assessment of PE in CTPA.
The presence of distant metastases has long been a predictor of poor outcome in solid cancer. However, in an oncologic situation called oligometastatic disease (OMD), multiple studies have revealed a ...survival benefit with aggressive treatment of these metastases. Besides surgery and radiation therapy, local thermal therapies have developed into a treatment option for OMD. Most studies concerning local therapy of OMD are available for colorectal cancer, which is therefore the focus of this article. Furthermore, this review gives a basic overview of the most popular ablation techniques for treatment of OMD.
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