Die tumorbedingte Mangelernährung und Kachexie ist ein Syndrom mit sowohl medizinischer als auch gesundheitsökonomischer Relevanz. In den letzten Jahren wurde ein besseres Verständnis für die komplexe Pathophysiologie, bestehend aus Stoffwechselstörungen, verminderter Energiezufuhr und Entzündungsprozessen, die zum fortschreitenden Muskel- und Fettmassenverlust führen, erreicht. Dieses Verständnis dient bis heute der Entwicklung möglicher präventiver und therapeutischer Ansätze. Geeignete Screening-Tests tragen dazu bei, das Syndrom rechtzeitig zu erkennen und weitere Maßnahmen einzuleiten. Da der Muskel- und Fettmassenverlust nicht immer durch einen reinen Gewichtsverlust gekennzeichnet ist, ist die Erfassung der Körperzusammensetzung ein wesentlicher Bestandteil in der Betreuung onkologisch Erkrankter. Die BIA ist ein hierfür geeignetes Verfahren, welches leicht in den klinischen Alltag zu integrieren ist und besonders zur interindividuellen Verlaufskontrolle herangezogen werden könnte. Ernährungsmedizinische und bewegungstherapeutische Maßnahmen sind bereits fester Bestandteil internationaler Leitlinien. Für pharmakologische Therapiekonzepte besteht noch weiterer Forschungsbedarf, um eine Arzneimittelzulassung zu erreichen. Eine alleinige Intervention ist in der Behandlung der onkologischen Mangelernährung und Kachexie wenig effektiv. Deshalb müssen die Bedeutung und der potentielle Nutzen einer Kombination der einzelnen Behandlungsbausteine näher betrachtet werden, um eine bessere Evidenz zu erhalten. Der nachweisliche Mangel an Ernährungsstrukturen und ernährungsmedizinischer Fachkompetenz, Schwierigkeiten der Definitionsentwicklung und Gestaltung von Studien sowie finanzierungstechnische Fragen stellen ein zentrales Problem in der angemessenen Betreuung der Erkrankten dar. Jedoch bestehen klare Handlungsempfehlungen und Strategien, durch die entsprechende Herausforderungen reduziert oder beseitigt werden könnten. Dadurch profitieren sowohl Erkrankte als auch das Gesundheitssystem. Dies kann durch eine verbesserte Versorgung mittels Prävention, frühzeitiger Erfassung, Diagnose und Einleitung angebrachter Therapiemaßnahmen auf dem Gebiet der tumorbedingten Mangelernährung und Kachexie erreicht werden. / Cancer-related malnutrition and cachexia is a syndrome with both medical and health economic relevance. In recent years, a better understanding of the complex pathophysiology, consisting of metabolic disorders, reduced energy intake and inflammatory processes that lead to progressive muscle and fat mass loss, has been achieved. This understanding is still used today to develop possible preventive and therapeutic approaches. Suitable screening tests help to detect the syndrome in good time and initiate further measures. Since the loss of muscle and fat mass is not always characterized by just weight loss, the assessment of body composition is an essential component in the care of oncologically ill patients. The BIA is a suitable method for this, it is easy to integrate into everyday clinical practice and could be used in particular for inter-individual progress monitoring. Nutritional and exercise therapy measures are already an integral part of international guidelines. There is still a need for further research into pharmacological therapy concepts in order to obtain drug approval. Intervention alone is not very effective in the treatment of oncological malnutrition and cachexia. Therefore, the importance and potential benefits of a combination of the individual treatment components must be examined in more detail in order to obtain better evidence. The demonstrable lack of nutritional structures and nutritional expertise, difficulties in developing definitions and designing studies as well as funding issues represent a central problem in the appropriate care of patients. However, there are clear recommendations for action and strategies that could reduce or eliminate these challenges. This benefits both patients and the healthcare system. This can be achieved by improving care through prevention, early detection, diagnosis and initiation of appropriate therapeutic measures in the area of cancer-related malnutrition and cachexia.

Aims: The aim of this work was to determine whether a increased resting energy expenditure contributes to the nutritional risk for patients with pancreatic cancer. What the variability of resting energy expenditure is and whether it predicts weight loss. Another aim was to verify that lower protein-energy intake also has an impact on weight loss. Methods: Data for the diploma thesis were obtained from the project "Pancreatic Cancer: Metabolic Derangements Associated With Insulin Resistance", which takes place at the Department of Clinical Physiology of Metabolism at 2nd Department of internal medicine in the University Hospital Královské Vinohrady. The project includes 40 - 50 patients with pancreatic tumor resection per year. Data were collected from the beginning of December 2019 until the end of April 2020. The project is funded by the grant AZV NV19-01-00101. 10 consecutive patients (4 women and 6 men) with pancreatic cancer who had a complete dataset for analysis were selected for the research set for the diploma thesis. The patients underwent anthropometric examination, blood tests were taken, and indirect calorimetry was performed. Results: The first part of the research was focused on anthropometric parameters, parameters of nutritional status and the presence of cancer cachexia. The second...

The thesis is focused on the effect of ghrelin receptor (GHS-R1a) agonists and antagonist on food intake regulation. Ghrelin is the only known periferally produced orexigenic hormone and the only known acylated hormone. GHS-R1a agonists and antagonists could be useful in the treatment of cachexia and obesity, respectively. In the first part of the thesis, newly designed peptidic GHS-R1a agonists were characterized. The agonists were stabilized by replacing octanoylated Ser3 with a fatty acid coupled to diaminopropionic acid by a stable amide bond. Other noncoded amino acids were also incorporated. Ghrelin analogs were modified by replacing the octanoyl group with another fatty acid, incorporation of the second fatty acid or shortening the peptide chain. Most of the tested GHS-R1a agonists were found to possess high affinities for GHS-R1a (Ki = 10-9 - 10-10 nM) and to activate signaling pathways of ghrelin. After subcutaneous (SC) administration to mice, agonists showed significant and prolonged orexigenic effect. In the second part of the thesis, acute and long-term effects of pseudopeptide GHS-R1a agonist JMV1843 were tested in lean C57BL/6 mice. Acute SC administration of JMV1843 to fed mice increased food intake in a dose-dependent manner (ED50 = 1.94 mg/kg). JMV1843 was stable in blood serum in...

The thesis is focused on the effect of ghrelin receptor (GHS-R1a) agonists and antagonist on food intake regulation. Ghrelin is the only known periferally produced orexigenic hormone and the only known acylated hormone. GHS-R1a agonists and antagonists could be useful in the treatment of cachexia and obesity, respectively. In the first part of the thesis, newly designed peptidic GHS-R1a agonists were characterized. The agonists were stabilized by replacing octanoylated Ser3 with a fatty acid coupled to diaminopropionic acid by a stable amide bond. Other noncoded amino acids were also incorporated. Ghrelin analogs were modified by replacing the octanoyl group with another fatty acid, incorporation of the second fatty acid or shortening the peptide chain. Most of the tested GHS-R1a agonists were found to possess high affinities for GHS-R1a (Ki = 10-9 - 10-10 nM) and to activate signaling pathways of ghrelin. After subcutaneous (SC) administration to mice, agonists showed significant and prolonged orexigenic effect. In the second part of the thesis, acute and long-term effects of pseudopeptide GHS-R1a agonist JMV1843 were tested in lean C57BL/6 mice. Acute SC administration of JMV1843 to fed mice increased food intake in a dose-dependent manner (ED50 = 1.94 mg/kg). JMV1843 was stable in blood serum in...