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Cisplatin induces anorexia, weight loss, loss of adipose tissue, skeletal muscle atrophy, and serious adverse effects that can cause premature termination of chemotherapy. The aim of this study was to use an animal model to assess cisplatin therapy (3 cycles) with and without d-methionine to investigate its protective effects on cisplatin-induced anorexia and skeletal muscle wasting. Wistar rats were divided into 3 groups and treated as follows: saline as control (group 1), intraperitoneal cisplatin once a week for 3 weeks (group 2), and intraperitoneal cisplatin once a week for 3 weeks plus oral administration of d-methionine (group 3). Tissue somatic index (TSI), gastric emptying index (GEI), and feeding efficiency were measured. Both hepatic lipid metabolism and muscle atrophy-related gene expressions and C2C12 myotubes were determined by polymerase chain reaction. Micro–computed tomography (micro-CT) was used to conduct assessment of bone microarchitecture indices. Pathological changes of the gastric mucosa were assessed by hematoxylin and eosin staining after euthanizing the animals. d-Methionine increased food intake, weight gain, gastric emptying, and feeding efficiency, as well as decrease stomach contents, after cisplatin injections. Cisplatin caused shortening of myofibers. Cisplatin-induced muscle mass wasting was mediated by the elevation of mRNA expressions of MAFbx and MuRF-1 in ubiquitin ligases in muscle tissue homogenate. The mRNA expressions of MyoD and myogenin, markers of muscle differentiation, declined following cisplatin administration. The administration of d-methionine not only led to significant improvements in myofiber diameter and cross-sectional fiber areas but also reversed muscle atrophy-related gene expression. However, there were no significant changes in stomach histology or microarchitecture of trabecular bone among the study groups. The results indicate that d-methionine has an appetite-enhancing effect and ameliorates cisplatin-induced adipose and muscle tissue loss during cisplatin-based chemotherapy.

Lung cancer is the leading cause of cancer death. The endothelin-1 (EDN1)/endothelin A receptor (EDNRA) axis may directly contribute to tumor growth and indirectly modulate tumor–host interactions in various tumors. Since the genetic background between EDN1/EDNRA and non-small cell lung cancer (NSCLC) remains unknown. In this study, the association of genotypic polymorphisms in EDN1 and EDNRA with NSCLC was investigated. 388 patients with NSCLC and 396 healthy controls recruited from the China Medical Hospital in Taiwan were genotyped by a PCR-RFLP method. Results: Overall, the distribution of the genotype frequencies of EDN1 rs5370 G/T and EDNRA rs5333 T/C were significantly different between the lung cancer patients and the healthy controls, and also different between patients with lung cancers of various stages. Logistic regression analysis revealed that higher odds ratios (ORs) for lung cancer were seen for individuals with EDN1 rs5370 TT genotype against GG/GT genotypes (an OR of 4.22, 95% CI 2.68-7.02, p Conclusions: A significant association between the EDN1 rs5370 G/T and EDNRA rs5333 T/C genetic polymorphisms and the susceptibility to NSCLC was demonstrated. Also, these two polymorphisms were associated with the severity of lung cancer. The EDN1 rs5370 TT and EDNRA rs5333 CC genotypes have a promotive effect for lung cancer development and progression.