Kaşeksi, kanser hastalarında yüksek oranda morbidite ve mortaliteye sebep olan karmaşık bir metabolik sendromdur. Kaşeksi, çok sayıda fonksiyonel, metabolik ve immünolojik bozukluklarla seyretmekle kalmayıp tedavi toleransı ve toksisitesini de olumsuz etkilemektedir. Kanser kaşeksisinin oluşumunda interlökin-1 (IL-1), IL-6, tümör nekrozis faktörü-alfa (TNF-α) gibi proinflamatuar sitokinler ve TNF ile ilişkili zayıf apoptoz indükleyicisi reseptörü Fn14 rol oynamaktadır. Tümör hücrelerince üretilen lipid mobilize edici faktör, yağ dokusunu azaltırken, kas kaybından ise ubikuitin ve Januskinaz-sinyal translasyon ve transkripsiyon yolağı ve kemik metastazlarında salgılanan transforme edici büyüme faktörü betanın katkısının olduğu düşünülmektedir. Bağırsak mikrobiyotasının da kaşeksi gelişiminde rol oynayabileceği düşünülmektedir. Kaşekside serotonin, dopamin, histamin ve kalsitonin gen-ilişkili peptid gibi nörotransmitterlerin ve ghrelin, leptin, kortikotropin salıcı faktör, nöropeptid Y, alfa-melanosit uyarıcı hormon gibi hormonların artışı sonucunda anoreksiye yatkınlık oluşmaktadır. Kanser kaşeksisinde kas kaybının yanında göz ardı edilen birçok klinik etki vardır. Kalp yetersizliği, trombositoz ve endotel geçirgenliğinde artış sonucunda oluşan koagülasyona yatkınlık mortaliteye sebep olabilmektedir. Kanser hastalarında artan glukoneogenez, artmış ghrelin üretimi, testosteron eksikliği ve düşük D vitamini seviyeleri glukoz metabolizmasının değişmesine katkıda bulunabilir. Kaşekside nöropati ve otonomik disfonksiyon da oluşabilir. Kaşekside hepatosteatoz ve psikososyal problemler de ortaya çıkabilmektedir. Kanser kaşeksisi patogenezi konusunda daha fazla araştırmaya ihtiyaç duyulmaktadır. Özellikle kanser hastalarını takip eden klinisyen hekimler bu süreci daha doğru yönetebilmek için kaşeksi etiyopatogenezi ve göz ardı edilen klinik bulgular konusunda bilgi sahibi olmalıdır.
Anahtar Kelimeler: Kanser; kaşeksi; etiyopatogenez; komplikasyonlar
Cachexia is a complicated metabolic syndrome, characterized by increased morbidity and mortality in cancer patients. Many functional, metabolic and immunological disorders accompany, and also the tolerance and toxicities of treatments are negatively affected in cancer cachexia. Proinflammatory cytokines such as interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-α) and TNF-related weak apoptosis inducer receptor Fn14 play a role in the formation of cancer cachexia. While lipid mobilizing factor produced by tumor cells reduces adipose tissue, it is thought that ubiquitin and Janus kinase-signal translation and transcription pathway and transforming growth factor beta secreted in bone metastases contribute to muscle loss. Intestinal microbiata mat also have a role in the etiopathogenesis of cachexia. In cachexia, a predisposition to anorexia occurs as a result of the increase in neurotransmitters such as serotonin, dopamine, histamine and calcitonin gene-related peptide, and hormones such as ghrelin, leptin, corticotropin-releasing factor, neuropeptide Y, alpha-melanocyte stimulating hormone. Among many ignored clinical effects of cancer cachexia, cardiac insufficiency, hypercoagulation secondary to thrombocytosis and increased endothelial permeability can be mentioned. Increased gluconeogenesis, increased ghrelin production, testosterone deficiency, and low vitamin D levels in cancer patients may contribute to altered glucose metabolism. In cachexia, neuropathy and autonomic dysfunction can emerge hepatosteatosis as psychosocial problems can be seen in cachectic patients. Especially the clinicians who treat and follow the cancer patients should be more acknowledged on the etiopathogenesis and clinically ignored complications of cachexia for better management of this process.
Keywords: Cancer; cachexia; ethiopathogenesis; clinical complications
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