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Die Umgestaltung der Tumor-Mikroumgebung, die Modulation nicht-maligner Zellen sowie die Induktion des metastatischen Potentials sind essentielle Vorgänge im Rahmen der Tumorprogression. Exosomen sind extrazelluläre Vesikel eines Durchmessers von 50-150 nm, welche im Rahmen des interzellulären Informationsaustauschs eine möglicherweise maßgebliche Rolle in Tumorwachstum und Malignitätssteigerung innehaben. Ein genaueres Verständnis ihrer Funktion könnte zu neuen diagnostischen und therapeutischen Möglichkeiten in der Onkologie verhelfen. Im Rahmen dieser Arbeit erfolgte die Charakterisierung von Exosomen aus Prostatakarzinom (PCa)-Zellen auf molekularer und funktioneller Ebene. Exosomen aus den PCa-Zelllinien LNCaP, PC-3 und PC3-HSP27 wurden anhand Ultrazentrifugation angereichert. Es erfolgte eine Validierung der Präparationsmethode mittels dynamischer Lichtstreuung und Transmissionselektronenmikroskopie. Das exosomale Transkriptom wurde anhand DNA-Microarray, das exosomale Proteom anhand Massenspektrometrie analysiert. Der Auswirkung von PCa-Exosomen auf ihre Umgebung wurde mittels MTT-Vitalitätstest und LDH-Zytotoxizitätstest nachgegangen. Anhand der SILAC-Methodik erfolgte der Nachweis einer Aufnahme exosomaler Proteine in canine Zellen. Die Analyse der exosomalen Nukleinsäuren- und Protein-Zusammensetzung zeigte, dass Exosomen einerseits einen Fingerabdruck des Zytoplasmas der Ursprungszelle darstellen und, dass andererseits eine spezifische Anreicherung von Membranproteinen stattfindet. Dabei erschien vor allem die Inkorporation kleiner Proteine keinem bestimmten Sortierungsmechanismus zu unterliegen. Die Zellkultur-Experimente ließen auf einen Wachstums-inhibierenden Effekt der Exosomen kanzerösen Ursprungs auf nicht-maligne Zellen schließen. Des Weiteren konnte eine Aufnahme exosomaler, humaner Proteine in canine Zellen nach einer Inkubationszeit von 6 h nachgewiesen werden. In der Zusammenschau weisen die Ergebnisse auf eine bedeutende Funktion der Exosomen im Rahmen der Modulation der PCa-Mikroumgebung hin. Exosomen ist die Induktion multipler Effekte in Tumor-assoziierten Zielzellen zuzuschreiben, unter anderem die Regulation des Zellwachstums.
AbstractPlasma medicine refers to the application of nonequilibrium plasmas at approximately body temperature, for therapeutic purposes. Nonequilibrium plasmas are weakly ionized gases which contain charged and neutral species and electric fields, and emit radiation, particularly in the visible and ultraviolet range. Medically-relevant cold atmospheric pressure plasma (CAP) sources and devices are usually dielectric barrier discharges and nonequilibrium atmospheric pressure plasma jets. Plasma diagnostic methods and modelling approaches are used to characterize the densities and fluxes of active plasma species and their interaction with surrounding matter. In addition to the direct application of plasma onto living tissue, the treatment of liquids like water or physiological saline by a CAP source is performed in order to study specific biological activities. A basic understanding of the interaction between plasma and liquids and bio-interfaces is essential to follow biological plasma effects. Charged species, metastable species, and other atomic and molecular reactive species first produced in the main plasma ignition are transported to the discharge afterglow to finally be exposed to the biological targets. Contact with these liquid-dominated bio-interfaces generates other secondary reactive oxygen and nitrogen species (ROS, RNS). Both ROS and RNS possess strong oxidative properties and can trigger redox-related signalling pathways in cells and tissue, leading to various impacts of therapeutic relevance. Dependent on the intensity of plasma exposure, redox balance in cells can be influenced in a way that oxidative eustress leads to stimulation of cellular processes or oxidative distress leads to cell death. Currently, clinical CAP application is realized mainly in wound healing. The use of plasma in cancer treatment (i.e. plasma oncology) is a currently emerging field of research. Future perspectives and challenges in plasma medicine are mainly directed towards the control and optimization of CAP devices, to broaden and establish its medical applications, and to open up new plasma-based therapies in medicine.
Parental cancer poses major challenges for families with minor children. Due to diagnosis and treatment family life is disrupted. To prevent long-term consequences in all family members and to design needs-oriented family-centered interventions, further understanding of the family's situation including the impact on the children, quality of life levels and the parental psychosocial needs is necessary. This study aims at investigating the impact of parental cancer on the minor children, family-specific psychosocial needs and quality of life levels of parents and children. Cancer patients parenting at least 1 minor child (<18 years) were eligible for study participation. In total, n=86 cancer patients under treatment participated in the study. After excluding participants without a minor child, 78 patients remained for analyses. We assessed children's quality of life using the parent proxy version of the KIDSCREEN-10 and parental quality of life using the EORTC QLQ C30 quality of life questionnaire. Additionally, the questionnaire comprised open questions about positive and negative changes parents perceived in their children as well as questions on specific family- and child-related psychosocial needs. The majority of participants were mothers (91%), mainly diagnosed with breast cancer (59%). The participating parents provided data on 117 minor children. Parents mentioned positive changes in 38% of the children (e.g., being more attentive and helpful). Negative changes were reported in 37% of the children (e.g., being more anxious and clingy). Parents reported family-specific psychosocial supportive care needs for themselves as a parent (e.g., support regarding parenting concerns), support needs for the partner or the children. Moreover, parents expressed family-related information needs and needs regarding practical aspects (e.g., childcare, household help). Global quality of life was M = 55.7 (SD = 23.4) for parents and M = 57.5 (SD = 15.5) for children. Pearson's correlation coefficient between parental and children's quality of life was 0.377 (p < 0.001). To identify parents with cancer and children in need for additional support, health care providers should proactively inquire about the impact of the disease on the children. In terms of a comprehensive cancer care, the direct assessment of family impact and family-specific support needs in cancer patients with minor children allows for needs-based allocation to support offers.
This review assessed population-based estimate rates of cancer patients with minor and young adult children (≤ 25 years), children and young adults having a parent with cancer as well as the psychosocial situation and well-being of children and young adults affected by parental cancer. Eighteen publications on population-based studies were included. Studies varied in the age ranges of both cancer patients and children. The prevalence rates of cancer patients having children ranged from 14 to 24.7% depending on the sample structure (e.g., age, gender). Studies reported that between 1.6 and 8.4% of children resp. young adult children have a parent with a history of cancer. Seven publications reported on the psychosocial situation or well-being in children and young adults affected by parental cancer. Estimate rates of psychosocial problems, psychiatric diagnoses or distress ranged between 2.5 and 34% of children depending on the method of measurement and outcome. The differences in the sample structure between the studies impeded the comparison of prevalence rates. However, the findings help to determine the need for specific support services and health care planning. The results emphazise the importance to routinely include issues on the parental role of patients and questions on the well-being and coping of children into psychooncological care. If necessary, support should be provided to families living with a cancer diagnosis.
: Human osteosarcoma (OS) is the most common primary malignant bone tumor occurring
most commonly in adolescents and young adults. Major improvements in disease-free survival have
been achieved by implementing a combination therapy consisting of radical surgical resection of the
tumor and systemic multi-agent chemotherapy. However, long-term survival remains poor, so novel
targeted therapies to improve outcomes for patients with osteosarcoma remains an area of active
research. This includes immunotherapy, photodynamic therapy, or treatment with nanoparticles.
Cold atmospheric plasma (CAP), a highly reactive (partially) ionized physical state, has been shown
to inherit a significant anticancer capacity, leading to a new field in medicine called “plasma oncology.”
The current article summarizes the potential of CAP in the treatment of human OS and reviews the
underlying molecular mode of action.
Cold physical plasma is a partially ionized gas expelling many reactive oxygen and nitrogen
species (ROS/RNS). Several plasma devices have been licensed for medical use in dermatology, and
recent experimental studies suggest their putative role in cancer treatment. In cancer therapies with
an immunological dimension, successful antigen presentation and inflammation modulation is a
key hallmark to elicit antitumor immunity. Dendritic cells (DCs) are critical for this task. However,
the inflammatory consequences of DCs following plasma exposure are unknown. To this end,
human monocyte-derived DCs (moDCs) were expanded from isolated human primary monocytes;
exposed to plasma; and their metabolic activity, surface marker expression, and cytokine profiles
were analyzed. As controls, hydrogen peroxide, hypochlorous acid, and peroxynitrite were used.
Among all types of ROS/RNS-mediated treatments, plasma exposure exerted the most notable
increase of activation markers at 24 h such as CD25, CD40, and CD83 known to be crucial for T cell
costimulation. Moreover, the treatments increased interleukin (IL)-1α, IL-6, and IL-23. Altogether,
this study suggests plasma treatment augmenting costimulatory ligand and cytokine expression in
human moDCs, which might exert beneficial effects in the tumor microenvironment.