M & L Jaargang 3/6

RedactioneelW. Claes, A. De Haeck en G. Van der Linden De Japanse honingboom te Sint-Truiden (Kerkom). Boomverzorging als beheersmaatregel voor het behoud van ons onroerend patrimonium. [The Sophora japonica at Sint-Truiden (Kerkom). Tree care as preservation measure of our heritage.]Miek Goossens Het Oud Stadhuis van Blankenberge. [The old town hall of Blankenberge.]C. Vermeersch Het verdriet van Brugge. [The sorrow of Bruges.]Brussels detailRoger Deneef De Demervallei tussen Aarchot en Werchter. Deel 2. [The Demer valley between Aarschot and Werchter (part 2).]SummaryM&L Binnenkran

Does the proteasome inhibitor bortezomib sensitize to DNA-damaging therapy in gastroenteropancreatic neuroendocrine neoplasms? - A preclinical assessment in vitro and in vivo

BACKGROUND: Well-differentiated gastroenteropancreatic neuroendocrine neoplasms are rare tumors with a slow proliferation. They are virtually resistant to many DNA-damaging therapeutic approaches, such as chemo- and external beam therapy, which might be overcome by DNA damage inhibition induced by proteasome inhibitors such as bortezomib. METHODS AND RESULTS: In this study, we assessed several combined treatment modalities in vitro and in vivo. By cell-based functional analyses, in a 3D in ovo and an orthotopic mouse model, we demonstrated sensitizing effects of bortezomib combined with cisplatin, radiation and peptide receptor radionuclide therapy (PRRT). By gene expression profiling and western blot, we explored the underlying mechanisms, which resulted in an impaired DNA damage repair. Therapy-induced DNA damage triggered extrinsic proapoptotic signaling as well as the induction of cell cycle arrest, leading to a decreased vital tumor volume and altered tissue composition shown by magnetic resonance imaging and F-18-FDG-PET in vivo, however with no significant additional benefit related to PRRT alone. CONCLUSIONS: We demonstrated that bortezomib has short-term sensitizing effects when combined with DNA damaging therapy by interfering with DNA repair in vitro and in ovo. Nevertheless, due to high tumor heterogeneity after PRRT in long-term observations, we were not able to prove a therapeutic advantage of bortezomib-combined PRRT in an in vivo mouse model

Inter and intra-tumor somatostatin receptor 2 heterogeneity influences peptide receptor radionuclide therapy response

Patients with neuroendocrine tumors (NETs) can be treated with peptide receptor radionuclide therapy (PRRT). Here, the somatostatin analogue octreotate radiolabeled with lutetium-177 is targeted to NET cells by binding to the somatostatin receptor subtype 2 (SST2). During radioactive decay, DNA damage is induced, leading to NET cell death. Although the therapy proves to be effective, mortality rates remain high. To appropriately select more optimal treatment strategies, it is essential to first better understand the radiobiological responses of tumor cells to PRRT. Methods: We analyzed PRRT induced radiobiological responses in SST2 expressing cells and xenografted mice using SPECT/MRI scanning and histological and molecular analyses. We measured [177Lu]Lu-DOTA-TATE uptake and performed analyses to visualize induction of DNA damage, cell death and other cellular characteristics. Results: The highest accumulation of radioactivity was measured in the tumor and kidneys. PRRT induced DNA damage signaling and repair in a time-dependent manner. We observed intra-tumor heterogeneity of DNA damage and apoptosis, which was not attributed to proliferation or bioavailability. We found a strong correlation between high DNA damage levels and high SST2 expression. PRRT elicited a different therapeutic response between models with different SST2 expression levels. Heterogeneous SST2 expression levels were also confirmed in patient NETs. Conclusion: Hete

Multi-modal image registration: matching MRI with histology

Spatial correspondence between histology and multi sequence MRI can provide information about the capabilities of non-invasive imaging to characterize cancerous tissue. However, shrinkage and deformation occurring during the excision of the tumor and the histological processing complicate the co registration of MR images with histological sections. This work proposes a methodology to establish a detailed 3D relation between histology sections and in vivo MRI tumor data. The key features of the methodology are a very dense histological sampling (up to 100 histology slices per tumor), mutual information based non-rigid B-spline registration, the utilization of the whole 3D data sets, and the exploitation of an intermediate ex vivo MRI. In this proof of concept paper, the methodology was applied to one tumor. We found that, after registration, the visual alignment of tumor borders and internal structures was fairly accurate. Utilizing the intermediate ex vivo MRI, it was possible to account for changes caused by the excision of the tumor: we observed a tumor expansion of 20%. Also the effects of fixation, dehydration and histological sectioning could be determined: 26% shrinkage of the tumor was found. The annotation of viable tissue, performed in histology and transformed to the in vivo MRI, matched clearly with high intensity regions in MRI. With this methodology, histological annotation can be directly related to the corresponding in vivo MRI. This is a vital step for the evaluation of the feasibility of multi-spectral MRI to depict histological ground-truth

The joint evaluated fission and fusion nuclear data library, JEFF-3.3

The joint evaluated fission and fusion nuclear data library 3.3 is described. New evaluations for neutron-induced interactions with the major actinides $^{235}$U, $^{238}$U and $^{239}$Pu, on $^{241}$Am and $^{23}$Na, $^{59}$Ni, Cr, Cu, Zr, Cd, Hf, W, Au, Pb and Bi are presented. It includes new fission yields, prompt fission neutron spectra and average number of neutrons per fission. In addition, new data for radioactive decay, thermal neutron scattering, gamma-ray emission, neutron activation, delayed neutrons and displacement damage are presented. JEFF-3.3 was complemented by files from the TENDL project. The libraries for photon, proton, deuteron, triton, helion and alpha-particle induced reactions are from TENDL-2017. The demands for uncertainty quantification in modeling led to many new covariance data for the evaluations. A comparison between results from model calculations using the JEFF-3.3 library and those from benchmark experiments for criticality, delayed neutron yields, shielding and decay heat, reveals that JEFF-3.3 performes very well for a wide range of nuclear technology applications, in particular nuclear energy

Does the proteasome inhibitor bortezomib sensitize to DNA-damaging therapy in gastroenteropancreatic neuroendocrine neoplasms? – A preclinical assessment in vitro and in vivo

Background: Well-differentiated gastroenteropancreatic neuroendocrine neoplasms are rare tumors with a slow proliferation. They are virtually resistant to many DNA-damaging therapeutic approaches, such as chemo- and external beam therapy, which might be overcome by DNA damage inhibition induced by proteasome inhibitors suc

Atopic dermatitis and vitamin D: facts and controversies

Patients with atopic dermatitis have genetically determined risk factors that affect the barrier function of the skin and immune responses that interact with environmental factors. Clinically, this results in an intensely pruriginous and inflamed skin that allows the penetration of irritants and allergens and predisposes patients to colonization and infection by microorganisms. Among the various etiological factors responsible for the increased prevalence of atopic diseases over the past few decades, the role of vitamin D has been emphasized. As the pathogenesis of AD involves a complex interplay of epidermal barrier dysfunction and dysregulated immune response, and vitamin D is involved in both processes, it is reasonable to expect that vitamin D's status could be associated with atopic dermatitis' risk or severity. Such association is suggested by epidemiological and experimental data. in this review, we will discuss the evidence for and against this controversial relationship, emphasizing the possible etiopathogenic mechanisms involved.Univ Brasilia UNB, Brasilia, DF, BrazilFed Dist Hlth State Dept SES DF, Brasilia, DF, BrazilUniv Brasilia HUB UNB, Brasilia Univ Hosp, Brasilia, DF, BrazilSão Paulo Fed Univ UNIFESP, Brasilia, DF, BrazilSão Paulo Fed Univ UNIFESP, Brasilia, DF, BrazilWeb of Scienc