Immunotherapy in Gynecologic Cancers

During the last years, significant progress in the understanding of signaling pathways of immune cells has revive the field of immune therapy for cancer. In this chapter, we explain the recent immunotherapy-based strategies for the treatment of gynecological cancers including cervical cancer, endometrial cancer, ovarian cancer, and vulvar cancer. This work will mainly focus on emerging clinical data on immune checkpoint inhibitors. But also data on adoptive T cell therapies and vaccines will be presented. It is anticipated that in future biomarker-guided randomized trials will provide better approaches in terms of response and resistance to immune therapy. The use of combination therapy for gynecological cancer might be one possible approach to overcome resistance

Ereigniskorrelation auf energiebeschränkten mobilen Endgeräten

Der Einsatz von Systemen mit komplexer Ereignisverarbeitung ist heutzutage in vielen Gebieten der Informationstechnologie anzutreffen. Beispielsweise können mithilfe eines mobilen Stau-Warn-Systems Autofahrer vor einem Stauende gewarnt und folglich Auffahrunfälle vermieden werden. Ein solches CEP-System kann hinsichtlich der guten Prozessorleistung eines Smartphones lokal auf einem mobilen Endgerät ausgeführt werden, wobei der Akku des Smartphones dabei stark belastet wird. Im Gegensatz dazu besteht die Möglichkeit, die berechnungsintensive Ausführung des CEP-Operators in einer Infrastruktur durchzuführen. In diesem Fall entsteht jedoch eine hohe Netzwerk-Kommunikation, die ebenfalls den Akku des Smartphones stark beansprucht. In dieser Arbeit wird daher der Energieverbrauch eines CEP-Systems mit lokaler, auf einem Smartphone durchgeführter Ausführung eines CEP-Operators mit der Ausführung in einer Infrastruktur verglichen. Dabei werden CEP-Operatoren anhand spezifischer Merkmale, wie der Anzahl der eingehenden Ereignisströme, der Berechnungskomplexität sowie der Frequenz der Ereigniskorrelation, klassifiziert. Aufgrund der Konfiguration eines CEP-Operators kann folglich entschieden werden, ob sich dessen Ausführung in einer entfernten Infrastruktur oder lokal auf dem Smartphone energieeffizienter darstellt. Die durchgeführte Evaluation hat gezeigt, dass die Frequenz der Ereigniskorrelation maßgeblich für den Energieverbrauch des CEP-Systems verantwortlich ist. Die Berechnungskomplexität des CEP-Operators bei der Ereigniskorrelation hat hingegen einen geringen Einfluss auf den Energiebedarf des Systems

Die Wirkung von zerebral exprimiertem Interleukin-12 auf die Gliomentwicklung ineinem transgenes Mausmodell

Die vorliegende Arbeit untersucht die Wirkung von Interleukin-12 (IL-12) auf einen murinen stereotaktisch implantierten Hirntumor. Anhand zahlreicher Tumormodelle wurde bereits belegt, dass IL-12 eine Hemmung auf das Wachstum von Tumoren ausübt. Teilweise konnte dies auch schon im humanen Bereich gezeigt werden. Es wurde ein Tumormodell etabliert, bei dem 3x104 Gliomzellen vom Typ GL261 stereotaktisch in das Cerebellum von Versuchsmäusen implantiert wurden. Dann wurde untersucht, welche Wirkung eine transgene IL-12 Überexpression auf die Tumorabstoßung hatte. In der Literatur wurden zahlreiche Modelle beschrieben, welche Interleukin-12 mittels Viren, Genegun, Naked-DNA-Injektion oder subkutaner Injektion von extern dem Organismus zuführen. An unserem Modell untersuchten wir die endogene Überexpression von IL-12 im Cerebellum. Unsere Ergebnisse zeigten, dass die GF-IL 12 tg Versuchstiere deutlich weniger Symptome hatten als Wildtyptiere. Im Durchschnitt waren die Tumorvolumina in den GF-IL 12 tg Versuchstieren um 64% kleiner als in den Wildtyptieren. Dies war statistisch signifikant. (p ≤ 0,0013, Mann Whitney U-Test). In den immunohistochemischen Untersuchungen demonstrierten wir, dass vor allem CD8+ T-Zellen das Tumorgewebe in den GF-IL 12 tg Versuchstieren infiltriert hatten. Spätere Depletionsexperimente unterstrichen die entscheidende Rolle der CD8+ TZellen. Zudem konnten wir die Suppressorfunktion der CD4+ T-Zellen auf die CD8+ Zellen nachweisen. Anhand von CRAG-Tieren untersuchten wir die Rolle der NKZellen, welche in diesem Modell eine untergeordnete Rolle spielten. Schließlich konnten wir mit IFN-gamma-K.O.-Tieren zeigen, dass für eine Rekrutierung von CD8+ T-Zellen und eine Tumorabstoßung IFN-gamma nicht gebraucht wird. Die Standard-Therapie maligner Gliome ist auch in heutiger Zeit immer noch die chirurgische Resektion sowie eine anschließende Chemotherapie und Radiotherapie. Hier könnte eine Immuntherapie mit IL-12 bessere Verläufe ermöglichen. Die vorliegende Arbeit zeigt Grundlagen auf, wie eine endogene IL-12 Produktion eine Tumorabstoßung vermittelt. Die IL-12 Therapien bei malignen Gliomen im humanen Bereich sind allerdings noch im Studienstadium

Clinical and pathological factors and outcome of central nervous system metastasis in breast cancer

BackgroundIn Switzerland, approximately 6000 new breast cancer cases and 1300 deaths are reported annually. Brain metastasis from breast cancer (BMBC) has a major effect on prognosis. This study aimed to identify prognostic factors for overall survival (OS) in a cohort of Swiss patients with BMBC. This study evaluated the prognosis on older BMBC, which has not been completely addressed in the literature.MethodsWe performed a retrospective chart review analysis with the primary endpoint of OS after a diagnosis of BMBC. The study population was divided into 2 groups based on an OS cut-off value of 12 months after diagnosis. Univariate and multivariate analyses of several risk factors, including age, were performed. To evaluate differences in OS according to age, we performed a secondary analysis to examine the prognostic value of clinical symptoms, metastatic pattern, and lymph node involvement in an older (≥65 years) vs. younger (<65 years) cohort.ResultsFrom 1989 to 2019, 55 patients were identified as having BMBC, among whom 47 patients were confirmed to be dead. The median patient age was 58 years (range 25–83 years). Comorbidities were present in 45 (81.8%) patients. The median survival in the OS <12 and OS ≥12 months groups was 4.3 and 30.7 months, respectively (p<0.001). Multivariate analysis revealed no significant differences in terms of comorbidities, medication use, M-stage, and symptomatology between the 2 groups. Additionally, there was no significant difference in OS in the 2 subgroups of patients aged <65 and ≥65 years.DiscussionWe concluded that age should not be a decisive factor in therapy planning for advanced breast cancer patients with BMBC

Changes in the quality of life of early breast cancer patients and comparison with the normative Slovenian population

We aimed to identify changes in quality of life after breast cancer treatment and compare them withthe normative population data for the Slovenian population.Patients and methods. A prospective, single-group, cohort design was used. A total of 102 early breast cancerpatients treated with chemotherapy at the Institute of Oncology Ljubljana were included. Of those, 71% returned thequestionnaires after one-year post-chemotherapy. The Slovenian versions of the European Organisation for Researchand Treatment of Cancer (EORTC) QLQ C30 and BR23 questionnaires were used. Primary outcomes were a com-parison of global health status/quality of life (GHS) and C30 Summary Score (C30-SumSc) at baseline and one-yearpost-chemotherapy with the normative Slovenian population. The exploratory analysis evaluated the differences insymptoms and functional scales of QLQ C-30 and QLQ BR-23 between baseline and one-year post-chemotherapy.Results. At baseline and one-year post-chemotherapy, C30-SumSc of patients was lower than the predictedC30-SumSc from the normative Slovenian population by 2.6 points (p = 0.04) and 6.5 points (p < 0.001), resp. On thecontrary, GHS was not statistically different from predicted either at baseline or after one year. Exploratory analysisrevealed that one-year post-chemotherapy compared to the beginning of chemotherapy, patients had statisticallysignificantly and clinically meaningful lower scores in body image and cognitive functioning, and increased symptomscores for pain, fatigue, and arm symptoms.Conclusions. The C30-SumSc is reduced one- year post-chemotherapy. Early interventions should be directed to-ward the prevention of the decline of cognitive functioning and body image, and to alleviate fatigue, pain, and armsymptoms

Individual and developmental differences in the relationship of preferences and theory of mind

Theory of mind and individual preferences are important determinants in social decision making. The current study examined in a large sample whether being a cooperative preference type is related with better theory of mind skills. Furthermore, by testing adolescents and adults, we examined the impact of age on this relation. Theory of mind is measured in a Public Goods Game. Results indicate that the cooperative type predicted other players. preference types more accurately in the first round of the Public Goods Game. Regarding age differences, cooperative adults estimated the behavior of players of the same type better than cooperative adolescents. Adolescents show lower cooperation levels and a slower adaption of behavior than adults indicating ongoing development of theory of mind in adolescence

Hodgkin's Lymphoma and Paraneoplastic Phenomena in the Central Nervous System: A Case Report and Review of the Literature

A 25-year-old male patient presented to our Ear, Nose and Throat clinic with a history of nausea, vomiting, headache, vertigo and weight loss of 5 kg over the preceding 3 months. An enlarged cervical lymph node was detected at clinical examination. Lymph node biopsy showed nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL, nodular paragranuloma). Because of the neurological symptoms a cerebral MRI scan was performed and revealed an intense perivascular, bilateral, contrast-medium enhancing lesion of the temporal lobes suggestive of cerebral vasculitis. Cerebrospinal fluid analysis showed an increased number of mononuclear cells, but there was no indication for neurotropic viral or bacterial infections. EEG revealed a left temporal epileptic focus, and anti-epileptic therapy was initiated. NLPHL was treated with 2 cycles of ABVD chemotherapy and 20 Gy involved-field radiotherapy. Steroid therapy (prednisone 100 mg q.d.) for the presumed paraneoplastic neurological manifestation was started 1 week before chemotherapy and led to the rapid disappearance of complaints. Because of renewed onset of nausea and vertigo after 3 weeks of treatment with ABVD chemotherapy and 4 weeks of treatment with steroids, a follow-up brain MRI and EEG were performed and demonstrated complete disappearance of the ‘vasculitic’ changes without additional pathologic findings. Five months after therapy, the patient is without neurological symptoms and a PET-CT showed a complete remission. This case is a unique example of paraneoplastic central nervous system (CNS) involvement in a patient with newly diagnosed NLPHL. We present a review of the literature on paraneoplastic CNS symptoms in Hodgkin's lymphoma

Perspective Chapter: Management of Bone Health in Breast Cancer Patients

Breast cancer is the most common cancer in the world. There are several implications of bone health in early and late breast cancer cases. In early breast cancer, the therapy might cause reduction of bone mineral density due to early menopause induction or as a side effect of therapy options, such as aromatase inhibitors. In late-stage breast cancer, most common site of metastasis is in the skeletal bone. Early management of bone metastasis needs special focus because of skeletal-related complications such as fractures, pain, hypercalcemia, and surgery. This chapter will focus on most common diagnostic and therapeutic measures of osseous metastasis, in early and advanced breast cancer

Digital twin based design and experimental validation of a continuous peptide polishing step

Optimizing or debottlenecking existing production plants is a challenging task. In this case study, an existing reversed phased chromatography polishing step for peptide purification was optimized with the help of a digital twin. The existing batch chromatography was depicted digitally with the general rate model. Model parameter determination and model validation was done with dedicated experiments. The digital twin was then used to identify optimized process variants, especially continuous chromatography steps. MCSGP was found to achieve high purities and yield but at the cost of productivity due to column synchronization. An alternative Continuous Twin Column chromatography process (CTCC) was established that eliminates unnecessary waiting times. Ensuring the same or higher purity compared to the batch process, the continuous process achieved a yield increase of 31% and productivity increase of 27.6%. Experimental long runs confirmed these results