Acute Motor Axonal Neuropathy in a Patient with Metastatic Pancreatic Neuroendocrine Tumor Receiving Chemotherapy with Capecitabine and Temozolomide: A Case Report

We report a case of a 37- year old female patient with metastatic pancreatic neuroendocrine tumor that developed acute motor axonal neuropathy after receiving chemotherapy with capecitabine and temozolomide. She had repeatedly progressed after several surgical resections of her liver metastases, other hepatic directed procedures, several sessions of peptide receptor radionuclide therapy and two systemic treatment lines. When we started a third line therapy with capecitabine (1500 mg absolute twice daily, day 1-14) and temozolomide (360 mg absolute in two divided doses on day 1-5) in a 28 days long cycle, she unexpectedly developed a progressive weakness of the upper and lower limbs and dysphagia. The diagnosis of acute motor axonal neuropathy was confirmed by nerve conduction studies. The patient`s condition improved rapidly after chemotherapy was stopped and plasma exchange (nine sessions) as well as a maintenance therapy with intravenous immunoglobulins was started. She was almost asymptomatic seven months after onset of symptoms. This case describes a previously unreported association between acute motor axonal neuropathy and chemotherapy with capecitabine and temozolomide

Aberrant Lck Signal via CD28 Costimulation Augments Antigen-Specific Functionality and Tumor Control by Redirected T Cells with PD-1 Blockade in Humanized Mice

Combination therapy of adoptively transferred redirected T cells and checkpoint inhibitors aims for higher response rates in tumors poorly responsive to immunotherapy like malignant pleural mesothelioma (MPM). Only most recently the issue of an optimally active chimeric antigen receptor (CAR) and the combination with checkpoint inhibitors is starting to be addressed. Fibroblast activation protein (FAP)-specific CARs with different costimulatory domains, including CD28, Δ-CD28 (lacking lck binding moiety), or 4-1BB were established. CAR-T cells were characterized and antitumor efficacy was tested in a humanized mouse model in combination with PD-1 blockade. Finally, the Δ-CD28 CAR was tested clinically in a patient with MPM. All the three CARs demonstrated FAP-specific functionality Gene expression data indicated a distinct activity profile for the Δ-CD28 CAR, including higher expression of genes involved in cell division, glycolysis, fatty acid oxidation, and oxidative phosphorylation. only T cells expressing the Δ-CD28 CAR in combination with PD-1 blockade controlled tumor growth. When injected into the pleural effusion of a patient with MPM, the Δ-CD28 CAR could be detected for up to 21 days and showed functionality. Overall, anti-FAP-Δ-CD28/CD3ζ CAR T cells revealed superior functionality, better tumor control in combination with PD-1 blockade in humanized mice, and persistence up to 21 days in a patient with MPM. Therefore, further clinical investigation of this optimized CAR is warranted

Transaktionsnutzen Transaktionsrisiken

Qualit\ue4tssicherungsma fnahmen bekommen eine immer gr\uf6 fere Bedeutung im europ\ue4ischen Lebensmittel- und Agrarsektor. Die Registrierung europ\ue4ischer Herkunftsangaben (EGH) unter der EU-Gesetzgebung verlangt kollektives Handeln der ProduzentInnen. Dabei entstehen verschiedene Transaktionsaufw\ue4nde, -nutzen und -risiken bei den beteiligten AkteurInnen. Den konzeptuellen Rahmen dieser explorativen Fallstudienanalyse bildet die Neue Institutionen\uf6konomik (Verf\ufcgungsrechte, Transaktionskosten\uf6konomik, Institutional Analysis and Development framework). Die Studie zum Mostviertler Birnmost g.g.A. ist Teil einer internationalen vergleichenden Fallstudienanalyse, die f\ufcnf EGH-Registrierungsprozesse in 6sterreich, Italien und Kolumbien miteinander vergleicht. Am Beispiel des Mostviertler Birnmosts g.g.A. zeigt die Masterarbeit die komplexen Faktoren, die das Verh\ue4ltnis von Transaktionsaufwand, -nutzen und -risiken beeinflussen. Dazu z\ue4hlen beispielsweise die Heterogenit\ue4t der AkteurInnen und Gruppengr\uf6 fe, die Marktsituation und Produktvolumina sowie die staatliche Unterst\ufctzung der AntragstellerInnen. Der Verzicht der ProduzentInnen auf die Nutzung des schlussendlich erfolgreich registrierten Herkunftsschutzes f\ufcr den Mostviertler Birnmost g.g.A. unterstreicht, dass f\ufcr den Erfolg von EGH sowohl die Initiative, die Motivation, das Engagement und die direkte Beteiligung der ProduzentInnen als auch ein gewisses Ma f an kollektivem Handeln sowie die professionelle Organisation des Registrierungsprozesses notwendig sind. F\ufcr die Unterst\ufctzung der AntragstellerInnen in 6sterreich w\ue4re die Etablierung einer eigens f\ufcr EGH zust\ue4ndigen Beratungsstelle sinnvoll. Da EGH in 6sterreich enge Verschr\ue4nkungen mit der nationalen Dachmarke Genuss Region 6sterreich aufweisen, w\ue4re - unter der Voraussetzung einer entsprechenden qualitativen und quantitativen Personalausstattung - die Zust\ue4ndigkeit der Genuss Region 6sterreich f\ufcr EGH denkbar.The registration of Geographical Indications (GIs) under the EU regulation requires collective action. The involved actors share various efforts, benefits and risks during this collective registration process. The explorative case study \u201cMostviertler Birnmost g.g.A .\u201d is guided by New Institutional Economics (Property rights theory, Transaction Cost Theory, Institutional Analysis and Development framework) and is part of an international cross-case comparison of five GI-processes in Austria, Italy and Colombia. The case study reveals that transaction efforts, benefits and risks are influenced by the heterogeneity of actors and group size, the market situation and product volume as well as public support of GIs. The \u2018Mostviertler Birnmost g.g.A.\u2019 is a good example to exhibit the complex interplay of these factors in a long-term registration process for the GIs, which resulted in the producers\u2019 final decision not to use the GI. By investigating the \u2018Mostviertler Birnmost g.g.A.\u2019 registration process it becomes evident that the success of GIs requires the initiative, the motivation, the engagement and direct involvement of the producers as well as a certain degree of collective action and the professional organization of the registration process. In order to support GI applicants in Austria the establishment of a specialized authority would be recommendable. Since GIs are closely linked to the intentions of the national label \u2018Genuss Region 6sterreich\u2019, the \u2018Genuss Region 6sterreich\u2019 GmbH could assume the responsibility of a consulting body for GIs given the precondition of an appropriate qualitative and quantitative staffing.eingereicht von: Magdalena PircherWien, Univ. f\ufcr Bodenkultur, Masterarb., 2015Zsfassung in engl. Sprach

T Cell Engineering

T cells are a new and promising antigen-specific therapeutic option for the treatment of malignant diseases. To achieve antigen specificity against tumor antigens, T cells can be manipulated by gene transfer to express chimeric antigen receptors (CARs). CAR-expressing T cells are called redirected T cells. CARs are composed of an extracellular antibody-derived antigen recognition domain, a transmembrane domain and a cytoplasmatic signal domain. Therefore, redirected T cells combine the exchangeable specificity of an antibody with the cytotoxic machinery of a T cell. Early clinical trials with redirected T cells targeting cluster of differentiation (CD) 19 have shown impressive results in CD19-positive hematological cancers. However, for solid cancers only limited clinical experience exists and new and innovative concepts have to be developed to overcome tumor-mediated immune suppression. Herein, we describe the general design of a CAR, the function of the different domains and the different strategies to produce redirected T cells. Furthermore, we summarize and discuss the preclinical and clinical data indicating the tremendous potential of redirected T cells to become a mainstay of cancer immunotherapy

Ovarian hyperstimulation and oocyte harvesting prior to systemic chemotherapy-a possible pitfall in 18F-FDG PET/CT staging of oncologic patients

A 33-year-old woman with Hodgkin disease Ann Arbor stage IIA underwent baseline F-FDG PET/CT scanning. The scan showed gross multicystic enlargement of both ovaries and a nodule at the edge of the right ovary with intense FDG uptake (SUVmax = 14.8). Differential diagnosis would include ovarian lymphoma manifestation, endometrioma, and ovarian or pelvic neoplasia. However, chart analysis revealed previous superstimulation with gonadotropins and gonadotropin release hormone antagonist, and transvaginal oocyte retrieval the day before FDG PET/CT. This led to the diagnosis of ovarian hyperstimulation syndrome, with the FDG-avid focus representing a hemorrhagic follicle after transvaginal oocyte retrieval procedure