Val103Ile polymorphism of the melanocortin-4 receptor gene (MC4R) in cancer cachexia

<p>Abstract</p> <p>Background</p> <p>At present pathogenic mechanisms of cancer cachexia are poorly understood. Previous evidence in animal models implicates the melanocortin-4 receptor gene (<it>MC4R</it>) in the development of cancer cachexia. In humans, <it>MC4R </it>mutations that lead to an impaired receptor function are associated with obesity; in contrast, the most frequent polymorphism (Val103Ile, rs2229616; heterozygote frequency approximately 2%) was shown to be negatively associated with obesity. We tested if cancer patients that are homo-/heterozygous for the Val103Ile polymorphism are more likely to develop cachexia and/or a loss of appetite than non-carriers of the 103Ile-allele.</p> <p>Methods</p> <p>BMI (body mass index in kg/m²) of 509 patients (295 males) with malignant neoplasms was determined; additionally patients were asked about premorbid/pretherapeutical changes of appetite and weight loss. Cachexia was defined as a weight loss of at least 5% prior to initiation of therapy; to fulfil this criterion this weight loss had to occur independently of other plausible reasons; in single cases weight loss was the initial reason for seeing a physician. The average age in years (± SD) was 59.0 ± 14.5 (males: 58.8 ± 14.0, females 59.2 ± 14.0). Blood samples were taken for genotyping of the Val103Ile by PCR- RFLP.</p> <p>Results</p> <p>Most of the patients suffered from lymphoma, leukaemia and gastrointestinal tumours. 107 of the patients (21%) fulfilled our criteria for cancer cachexia. We did not detect association between the Val103Ile polymorphism and cancer cachexia. However, if we exploratively excluded the patients with early leucaemic stages, we detected a trend towards the opposite effect (p < 0.05); heterozygotes for the 103Ile-allele developed cancer cachexia less frequently in comparison to the rest of the study group. Changes of appetite were not associated with the 103Ile-allele carrier status (p > 0.39).</p> <p>Conclusion</p> <p>Heterozygotes for the 103Ile-allele are not more prone to develop cancer cachexia than patients without this allele; possibly, Ile103 carriers might be more resistant to cancer cachexia in patients with solid tumors. Further studies of the melanocortinergic system in cachexia of patients with solid tumors are warranted.</p

Indicating Soil Quality Using Urease and Saccharase Activity in Abandoned Grassland and Differently Managed Crop Fields

In order to ascertain and make a comparison of bioactivity variation during vegetation period, soil samples were collected in fields of different fertilizing and farming systems: extensive (ExF), conventional (CF) and organic (OF) in order to determine the saccharase and urease activity responses to different land management systems and main soil quality indices: soil organic carbon (SOC), total nitrogen (N), and C/N ratio. Assessed hydrolases were observed as sensitivity indicators suitable to evaluate parameters of soil quality. The highest decrease and the lowest rates of urease (1.13 mg NH4 +–N g−1) and saccharase (8.40 mg CG g−1 24 h−1) activities were observed in abandoned grassland soil where mineral fertilizers were not applied. Enzyme activity correlated stronger with SOC (r = 0.7) or C/N ratio (r = 0.6) than that with total nitrogen content (r = 0.5 − 0.6). A significantly higher 3 year mean value of saccharase (27.00 and 12.6 mg CG g−1) and urease (5.78 and 4.16 mg NH4 +–Ng−1 24 h−1) activities were observed in soil under conventional and organic management compared with abandoned grassland. Thereafter enzyme activities might be related to the different levels of soil fertilityVytauto Didžiojo universitetasŽemės ūkio akademij