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A 50-year-old patient was admitted to our department after developing severe abdominal cramps, watery diarrhea and fever, during four days whilst travelling abroad. Imaging identified a mass in the ascending colon with simultaneous liver lesions. Initially a diagnosis of metastatic colorectal cancer was suggested, however colonoscopy showed a large lesion with a central ulcer and surrounding inflammation in the ascending colon. Biopsies confirmed our clinical suspicion of amoebic colitis, complicated by development of an amoeboma and simultaneous liver abscesses. Amoeboma formation is a rare complication of amoebiasis, however a simultaneous presentation with liver abscesses, amoebic colitis and an amoeboma might even be less frequent. Despite its rarity physicians should maintain a high index of suspicion of patients presenting with synchronous liver and colon lesions, especially as travel to endemic areas has increased. ispartof: ACTA GASTRO-ENTEROLOGICA BELGICA vol:82 issue:4 pages:539-541 ispartof: location:Belgium status: published

Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network. By bringing together biomedical professionals and parents as patient representatives, several collaborative DIPG-related projects have been realized. With help from experts in the fields of information technology, and legal advisors, an international, web-based comprehensive database was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence Interval (CI) 5.6–6.4 months) and the median overall survival is 11.0 months (95% CI 10.5–11.5 months). At two and five years post-diagnosis, 10 and 2% of patients are alive, respectively. The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG. This is seen as an essential first step towards understanding the disease, improving care and (ultimately) cure for children with DIPG. © 2017, The Author(s).

This paper examines how intonation affects the interpretation of disjunctive questions. The semantic effect of a question is taken to be three-fold. First, it raises an issue. In the tradition of inquisitive semantics, we model this by assuming that a question proposes several possible updates of the common ground (several possibilities for short) and invites other participants to help establish at least one of these updates. But apart from raising an issue, a question may also highlight and/or suggest certain possibilities, and intonation determines to a large extent which possibilities are highlighted/suggested.

Objective: The prognosis of patients with high-grade glioma (HGG) is dismal. We investigate the therapeutic role of vaccination with mature dendritic cells (DC) loaded with tumor lysates derived from resected tumor at the time of a relapse. Methods: Dendritis cells were injected intradermally according[for full text, please go to the a.m. URL], 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien

Objective: We have successfully treated over two hundred high-grade glioma (HGG) patients with adjuvant immunotherapy consisting of vaccination with autologous dendritic cells (DC) loaded with autologous tumor lysate. It has recently been shown that regulatory T cells (Treg) play an important role in[for full text, please go to the a.m. URL], 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien

Objective: In spite of neurosurgery, radiochemotherapy (RCT) and maintenance temozolomide chemotherapy (TZMm), the prognosis of patients with GBM remains poor. Because immunotherapy opened new perspectives for patients at time of relapse, we are integrating immunotherapy in the primary postoperative[for full text, please go to the a.m. URL], 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien

Occupancy of CTLA-4 (cytotoxic T-lymphocyte antigen-4 or CD152) negatively regulates the activation of mouse T lymphocytes, as indicated by the fate of CTLA-4-deficient mice, by the impact of anti-CTLA-4 monoclonal antibodies (mAbs) on mouse T-cell activation in vitro and by the impact of CTLA-4 blockade on the course of experimental tumoral, autoimmune, alloimmune or infectious disease in this animal. The function of human CTLA-4, however, remains less clear. The expression and function of human CTLA-4 were further explored. CTLA-4 was expressed under mitogenic conditions only, its expression being, at least partially, dependent on the secretion of interleukin-2. Memory T cells expressed CTLA-4 with faster kinetics than naive T cells. The functional role of human CTLA-4 was assessed utilizing a panel of four anti-CTLA-4 mAbs that blocked the interaction between CTLA-4 and its ligands. These mAbs, in immobilized form, profoundly inhibited the activation of T cells by immobilized anti-CD3 mAb in the absence of anti-CD28 mAb, but co-stimulated T-cell activation in the presence of anti-CD28 mAb. Finally, and importantly, blockade of the interaction of CTLA-4 with its ligands using soluble anti-CTLA-4 mAbs, in intact form or as Fab fragments, enhanced T-cell activation in several polyclonal or alloantigen-specific CD80- or CD80/CD86-dependent assays, as measured by cytokine production, cellular proliferation or cytotoxic responses. It is concluded that interaction of CTLA-4 with its functional ligands, CD80 or CD86, can down-regulate human T-cell responses, probably by intracellular signalling events and independent of CD28 occupancy.

gamma-Butyrobetaine hydroxylase catalyse the last step in carnitine biosynthesis, the formation of L-carnitine from gamma-butyrobetaine, a reaction dependent on Fe2+, alpha-ketoglutarate, ascorbate and oxygen. Initial attempts to purify the protein from rat liver showed that gamma-butyrobetaine hydroxylase is unstable. We, therefore, determined the influence of various compounds on the stability of gamma-butyrobetaine hydroxylase at different storage temperatures. The enzyme activity was best conserved by storing the protein at 4 degrees C in the presence of 200 g/l glycerol and 10 mM DTT. We subsequently purified the enzyme from rat liver to apparent homogeneity by liquid chromatography

Diverse auteurs gaan in op aspecten rondom scheiding

Being diagnosed with glioblastoma (GBM) is related to a grim future, with patients showing a median overall survival of less than 15 months despite intensive radio- and chemotherapy. As a consequence, the scientific community is searching for adjuvant treatment modalities that might improve the outcome of this devastating disease. In this regard, immunotherapy has gained great interest. One immunotherapeutic strategy uses dendritic cells (DCs) to generate an anti-tumor response induced by the patient's own immune system. This DC-based active immunotherapy consists of two groups using either ex vivo grown DCs or in vivo targeting of these cells. The latter condition might be preferred because of efficiency, variable response rates of ex vivo grown DCs plus limited migration to lymphoid tissue, as well as practical and economic reasons (time-consuming, labour-intensive process requiring sterile handling leading to an expensive vaccine). In order to induce a broader immune response against the cancer cells and because of the strong heterogeneity of these tumors, whole tumor cell lysate is being preferred as an antigenic source in glioma. Moreover, we were wondering if the tumor lysate vaccination could benefit from the implementation of nanoparticles (NPs) in this treatment. These small particles are able to improve DC immunotherapy for example by their variable physicochemical properties, by combining antigen and adjuvant internalisation and by rendering the opportunity to target DCs in vivo. To achieve this goal, a nanovaccine was generated by surface loading polystyrene NPs with whole tumor lysate and this way aiming for a passive targeting of DCs following subcutaneous injection. Based on the knowledge our research group obtained concerning the strength of the immunogenic signature of our lysate product, we investigated the potential effect and immune mechanisms of naked autologous immunogenic tumor lysate and lysate-NP conjugates, without the addition of DCs or adjuvants, to treat GBM in a preclinical mouse model. Following proof of antigen internalisation by DCs in vitro and subsequent antigen processing and presentation, a positive survival effect in preclinical murine glioma models was observed by subcutaneous lysate injections. Next, the process of nanovaccine generation was started by stably conjugating lysate to the surface of NPs. Following an optimisation process which judged size, antigen conjugation, in vitro DC internalisation and, in a limited manner, toxicity, the most ideal nanovaccine composition was tested in the glioma mouse models. Comparable results as for autologous lysate treatment were observed, showing survival benefit of subcutaneous nanovaccine administrations. In both treatment modalities, the immune response was characterized by an increase of T cells and a diminished immune suppression in the brain, with the induction of a tumor-specific immunological memory. Finally, combinatorial treatment strategies of autologous lysate vaccination or nanovaccine with TMZ chemotherapy lead to ameliorated survival outcome in glioma-bearing mice. The presented work demonstrated that subcutaneous injection of autologous whole tumor lysate can dose-dependently initiate an immune response that suppresses tumor growth of gliomas. The effectiveness of lysate treatment for gliomas offers a time and cost-effective approach in comparison to DC therapy, and thus it should be considered as a potential adjuvant treatment for glioma. With the nanovaccine research we aimed for a feasibility proof-of-concept study for using lysate-loaded NPs in the treatment of GBM that can be expanded in future. Further optimisation of a nanovaccine e.g. by co-delivery of antigens and immune adjuvants or active targeting of DCs, might be the future for autologous lysate vaccination. status: published

The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called "damage-associated molecular patterns" (DAMPs). The emission of DAMPs and other immunostimulatory factors by cells succumbing to immunogenic cell death (ICD) favors the establishment of a productive interface with the immune system. This results in the elicitation of tumor-targeting immune responses associated with the elimination of residual, treatment-resistant cancer cells, as well as with the establishment of immunological memory. Although ICD has been characterized with increased precision since its discovery, several questions remain to be addressed. Here, we summarize and tabulate the main molecular, immunological, preclinical, and clinical aspects of ICD, in an attempt to capture the essence of this phenomenon, and identify future challenges for this rapidly expanding field of investigation. ispartof: Frontiers in Immunology vol:6 issue:NOV ispartof: location:Switzerland status: published