Zusammenfassung
Kachexie beschreibt einen „schlechten Zustand” eines Patienten; dieses Syndrom kann
bei chronischen benignen Erkrankungen (wie Morbus Crohn, Herzinsuffizienz, chronischen
Nierenerkrankungen) sowie malignen Erkrankungen auftreten und stellt einen wesentlichen
prognostischen Faktor dar. Anhand der vorliegenden Publikation soll der aktuelle Stand
der Forschung zu pathophysiologischen Mechanismen der Kachexie insbesondere beim Pankreaskarzinom
dargelegt werden. Der Gewichtsverlust bei malignen Erkrankungen ist vor allem auf
Anorexie mit daraus resultierender Mangelernährung und einen progredienten Abbau von
Muskel- und Fettgewebe zurückzuführen. An dieser Entwicklung sind verschiedene Zytokine
beteiligt (u. a. TNF-α, IFN-γ, IL-1, IL-6). Über den Ubiquitin-Proteasom-Signalweg
wird der wesentliche Anteil des Proteins abgebaut, in diesen greift auch der Proteolysis
inducing Factor (PIF) ein; der Nachweis erhöhter Mengen einer hormonabhängigen Lipase
bei kachektischen Tumorpatienten weist darauf hin, dass ein gesteigerter Fettkatabolismus
für den Verlust von Fettgewebe wichtig zu sein scheint. Die Entwicklung einer effektiven
pharmakologischen Therapie stellt die zentrale klinische Herausforderung dar; bisher
konnte keine einen lang anhaltenden Effekt auf das Überleben bei Patienten mit einer
Tumorkachexie erbringen. Kachexie ist eine schwerwiegende Erkrankung, die besonders
häufig bei Patienten mit Pankreaskarzinom auftritt. Die Kachexie beeinträchtigt nachhaltig
die Lebensqualität und verschlechtert wesentlich die Prognose. Ziel der Forschung
muss sein, in zentrale Stellen der Kachexie-Regelkreise einzugreifen.
Abstract
Cachexia is a term used to describe the poor status of a patient suffering from a
benign disease (Crohn’s disease, chronic heart and kidney failure) as well as from
a malignant disease. Cachexia has an important impact on the survival and morbidity
in patients with cancer. The aim of this study is to elucidate the pathophysiology
in cancer cachexia with a special emphasis on pancreatic cancer. The dramatic weight
loss in malignant diseases is due to anorexia resulting in malnutrition and is characterised
by a progressive loss of muscle and fat tissue. Different cytokines like TNF-α, IFN-γ,
IL-1, IL-6 are involved in this process. Via the ubiquitin-proteasome pathway, in
which also the proteolysis inducing factor (PIF) is involved, the majority of protein
is degraded. In patients with cancer cachexia we find an elevated level of lipases,
which indicates that rather fat catabolism and not reduced fat synthesis is the main
factor in fat metabolism. The development of an effective (pharmacological) treatment
is still the main challenge. As yet, none of the used therapies show a long-lasting
effect on weight stabilisation and survial. Cachexia is an important issue, especially
in pancreatic cancer; it influences the qualitiy of life and has an important impact
on survival. Today, there are only a few different pharmacological therapies used
in the treatment of cancer cachexia, but each and every single treatment has failed
to show a persistent effect on survival. The aim of research and treatment is to interrupt
the natural clinical course of cachexia.
Schlüsselwörter
Kachexie - Survival - Pankreaskarzinom - Gewichtsverlust
Key words
cachexia - survival - pancreatic cancer - loss of weight
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