The prognostic role of inflammation and hormones in patients with metastatic cancer with cachexia

Bilir, Cemil; Engın, Hüseyin; Çan, Murat; Temi, Yasemin Bakkal; Demirtaş, Derya

doi:10.1007/s12032-015-0497-y

Cited by 48 publications

(26 citation statements)

References 18 publications

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“…TNFα was most consistently increased in these patient populations, followed by IL-6, with IL-1β being less consistently increased 32, 33 . Our finding on the increase of serum TNFα and IL-6, but not IL-1β, in LLC tumor-bearing mice is similar to these patient data.…”

Section: Discussionmentioning

confidence: 81%

Toll-like receptor 4 mediates Lewis lung carcinoma-induced muscle wasting via coordinate activation of protein degradation pathways

Zhang

Liu

Ding

et al. 2017

Sci Rep

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Cancer-induced cachexia, characterized by muscle wasting, is a lethal metabolic syndrome with undefined etiology. Current consensus is that multiple factors contribute to cancer-induced muscle wasting, and therefore therapy requires combinational strategies. Here, we show that Toll-like receptor 4 (TLR4) mediates cancer-induced muscle wasting by directly activating muscle catabolism as well as stimulating an innate immune response in mice bearing Lewis lung carcinoma (LLC), and targeting TLR4 alone effectively abrogate muscle wasting. Utilizing specific siRNAs we observed that LLC cell-conditioned medium (LCM)-treated C2C12 myotubes underwent a rapid catabolic response in a TLR4-dependent manner, including activation of the p38 MAPK−C/EBPβ signaling pathway as well as the ubiquitin-proteasome and autophagy-lysosome pathways, resulting in myotube atrophy. Utilizing a reporter cell-line it was confirmed that LCM activated TLR4. These results suggest that LLC-released cachexins directly activate muscle catabolism via activating TLR4 on muscle cells independent of immune responses. Critically, LLC tumor-bearing TLR4−/− mice were spared from muscle wasting due to a blockade in muscle catabolic pathways. Further, tumor-induced elevation of circulating TNFα and interleukin-6 (IL-6) was abolished in TLR4−/− mice. These data suggest that TLR4 is a central mediator and therapeutic target of cancer-induced muscle wasting.

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Section: Discussionmentioning

confidence: 81%

Toll-like receptor 4 mediates Lewis lung carcinoma-induced muscle wasting via coordinate activation of protein degradation pathways

Zhang

Liu

Ding

et al. 2017

Sci Rep

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“…Recruitment took place in four Belgian medical centres between 2012 and 2013: 1 Universitair Ziekenhuis Antwerpen (UZA; Edegem), 2 AZ Maria Middelares (Gent), 3 Heilig Hart Ziekenhuis Lier (Lier), 4 St Jozef Kliniek (Bornem). A total number of 167 patients started the study.…”

Section: Materials and Methods Patient Populationmentioning

confidence: 99%

“…[1][2][3][4][5] The prevalence of cancer cachexia is high: it is estimated to affect 50-80% of patients with cancer and accounts for up to 20% of deaths due to cancer in 2014. 3 The main clinical feature of cachexia is involuntary progressive weight loss as a result of reduction of skeletal…”

Section: Introductionmentioning

confidence: 99%

Cachexia in cancer: what is in the definition?

Vanhoutte

Wiel

Wouters

et al. 2016

BMJ Open Gastroenterol

112

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ObjectiveThis study aimed to provide evidence-based results on differences in overall survival (OS) rate to guide the diagnosis of cancer cachexia.DesignData collection and clinical assessment was performed every 3 months (5 visits): baseline data, muscle strength, nutritional and psychosocial status. 2 definitions on cachexia using different diagnostic criteria were applied for the same patient population. Fearon et al's definition is based on weight loss, body mass index (BMI) and sarcopenia. Evans et al nuances the contribution of sarcopenia and attaches additional attention to abnormal biochemistry parameters, fatigue and anorexia. The mean OS rates were compared between patients with and without cachexia for both definitions.ResultsBased on the population of 167 patients who enrolled, 70% developed cachexia according to Fearon et al's definition and 40% according to Evans et al's definition. The OS in the cachectic population is 0.97 and 0.55 years, respectively. The difference in OS between patients with and without cachexia is more significant using the diagnostic criteria of Evans et al. The focus of Fearon et al on weight loss and sarcopenia over-rates the assignment of patients to the cachectic group and OS rates have less prognostic value.ConclusionThis study presents a correlation with prognosis in favour of Evans et al’ definition as a tool for cachexia diagnosis. This means that weight loss and BMI decline are both key factors in patients with cancer leading to cachexia but less decisive as stated by Fearon et al. Instead, extra factors gain importance in order to predict survival, such as chronic inflammation, anaemia, protein depletion, reduced food intake, fatigue, decreased muscle strength and lean tissue depletion.Trial registration numberB300201112334.

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“…Recent studies suggest that the CD40-TRAF6 interaction leads to obesity-associated insulin resistance [81], which is a condition that induces muscle wasting. was shown to increase protein breakdown and inhibit protein synthesis [12], and elevated TNF-/ levels correlate with muscle loss in patients with cancer [1,2], COPD [3], and disuse [4]. The TNF chimeric monoclonal antibody infliximab, an agent that blocks TNF-/ action, can increase muscle strength and volume in patients with Crohn's disease [13], and long-term treatment with etanercept, another TNF-/ inhibitor, results in body weight gain in rheumatoid arthritis (RA) patients [14].…”

Section: Tnf-a In Conditions Promoting Muscle Wastingmentioning

confidence: 99%

“…TNF-/ is an inflammatory cytokine implicated in muscle wasting conditions associated with various diseases [1][2][3][4] and has been called cachexin, or cachectin, which refers to substances that cause severe body weight loss. TNF-/ is produced by different cell types including macrophages, lymphocytes, and skeletal muscle cells, and is involved in both local and systemic inflammation [5].…”

mentioning

confidence: 99%