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We have examined 63 methylcholanthrene (MCA)-induced mouse sarcomas for possible correlations of mutations involving the c-myc, ras and p53 genes. The c-myc gene was found to be amplified in 18 of these sarcomas (29%). Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and subsequent direct sequencing identified 18 cases carrying K-ras mutation at codons 12, 13 and 61 (29%). No mutation was detected in the H-ras and N-ras genes. Mutations of the p53 gene in exons 5 to 8 were found in 45 cases (71%). Comparison of these mutations revealed that out of 18 cases with c-myc gene amplifications, 10 carried K-ras mutations (56%) and 14 carried p53 mutations (78%). In contrast, among 45 cases of sarcomas without c-myc gene amplification, 8 were found to have K-ras mutations (18%). The same 45 cases were found to have 31 p53 mutations (69%). The present study suggests a strong correlation between c-myc gene amplification and K-ras gene mutation (P< < < <0.01). p53 gene mutation was frequently found among MCA-induced mouse sarcomas, indicating the importance of this mutation in the etiology of these tumors. However, p53 mutations were present in sarcomas regardless of the state of c-myc amplification and K-ras mutation. Therefore, a defect in the p53 gene is independent of amplification of the c-myc gene or point mutation of the K-ras gene.

Mutations of the p53 tumor suppressor gene are the most prevalent genetic alteration observed in a wide variety of human cancers. In this study we examined 63 methylcholanthrene (MCA)induced sarcomas from C57BL/6N× × × ×C3H/HeN F 1 (BCF 1 ) or C3H/HeN× × × ×C57BL/6N F 1 (CBF 1 ) mice for p53 gene mutations and loss of heterozygosity (LOH) of chromosome 11. Mutation analysis was done on exons 5 to 8 of the p53 gene by polymerase chain reaction-single strand conformation polymorphism analysis. This identified 53 potential mutations in 45 sarcomas. Mutations were further confirmed by direct sequencing of the region. Forty-nine of the 53 cases (94%) were missense mutations, while the rest included two nonsense mutations, one silent mutation and one insertional mutation. Spectra of base substitutions were: 25 cases (47%) of G:C→ → → →T:A transversion, 13 cases (25%) of G:C→ → → →A:T transition (CpG site 15%), 13 cases (24%) of G:C→ → → →C:G transversion, a case (2%) of A:T→ → → →T:A transversion and a case (2%) of insertion. In addition, analysis of 5 polymor-phic markers of mouse chromosome 11 revealed LOH in ten cases (22%) among those carrying p53 mutations. In nine of these 10 cases, the loss involved all 5 markers. In addition, the loss was biased toward the C57BL allele (9 cases). The present study establishes the pattern of mutation of the p53 gene in MCA-induced mouse sarcomas.

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Background Patients with end-stage renal disease (ESRD) are at an increased risk of developing sarcopenia, which can lead to various adverse health outcomes. Although the diagnosis of sarcopenia is essential for clinical management, it is not feasible in routine clinical practice for populations undergoing haemodialysis because it is time-consuming and resources are limited. Serum creatinine levels in patients with ESRD have been gaining attention as a screening parameter for sarcopenia because serum creatinine is a routinely measured byproduct of skeletal muscle metabolism. This study aimed to evaluate the discriminative ability of the creatinine-derived index for sarcopenia in patients undergoing haemodialysis. Methods We diagnosed sarcopenia according to the Asian Working Group for Sarcopenia (AWGS) 2 criteria in 356 clinically stable outpatients with ESRD enrolled from three dialysis facilities. We adopted the modified creatinine index as a simplified discriminant parameter for sarcopenia in addition to the calf circumference, SARC-F score, and combination of both (i.e. SARC-CalF score), which are recommended by the AWGS. Receiver operating characteristic analysis and logistic regression analysis were conducted to evaluate the discriminative ability of the modified creatinine index for sarcopenia. Results Of the study participants, 142 (39.9%) were diagnosed with sarcopenia. The areas under the curve of the modified creatinine index against sarcopenia in the male and female participants were 0.77 (95% confidence interval [CI]: 0.71 to 0.83) and 0.77 (95% CI: 0.69 to 0.85), respectively. All simplified discriminant parameters were significantly associated with sarcopenia, even after adjusting for patient characteristics and centre. In the comparison of the odds ratios for sarcopenia for 1-standard deviation change in the simplified discriminant parameters, the odds ratio of the modified creatinine index was 1.92 (95% CI: 1.15 to 3.19), which was lower than that of the calf circumference (odds ratio: 6.58, 95% CI: 3.32 to 13.0) and similar to that of the SARC-F (odds ratio: 1.57, 95% CI: 1.14 to 2.16) and SARC-CalF scores (odds ratio: 2.36, 95% CI: 1.60 to 3.47). Conclusions This study revealed a strong association between the creatinine-derived index and sarcopenia in patients undergoing haemodialysis. The modified creatinine index was equal or superior to those of SARC-F and SARC-CalF score in discriminability for sarcopenia. However, the ability of the calf circumference to discriminate sarcopenia is extremely high, and further study is needed to determine whether it can be used to detect deterioration of muscle mass and function over time.