CTNNB1 S45F Mutation Predicts Poor Efficacy of Meloxicam Treatment for Desmoid Tumors: A Pilot Study
50
Citation
35
Reference
10
Related Paper
Citation Trend
Abstract:
We hypothesized that patterns of CTNNB1 (β-catenin) mutations would affect the outcome of conservative therapy in patients with desmoid tumors. This study aimed to determine the significance of CTNNB1 (β-catenin) mutations in predicting the treatment outcome in patients with desmoid tumors treated with meloxicam, a cyclooxygenase-2 (COX-2) selective inhibitor. Between 2003 and 2012, consecutive thirty-three patients with extra-peritoneal sporadic desmoid tumors were prospectively treated with meloxicam as the initial systemic medical therapy. The efficacy of meloxicam was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). DNA was isolated from frozen tissue or formalin-fixed materials. CTNNB1 mutation analysis was performed by direct sequencing. Positivity of nuclear β-catenin staining by immunohistochemistry was compared with the status of CTNNB1 mutations. The correlation between the efficacy of meloxicam treatment and status of CTNNB1 mutations was analyzed. Of the 33 patients with meloxicam treatment, one showed complete remission (CR), 7 partial remission (PR), 12 stable disease (SD), and 13 progressive disease (PD). The following 3 point mutations were identified in 21 of the 33 cases (64%): T41A (16 cases), S45F (4 cases) and S45P (one case). The nuclear expression of β-catenin correlated significantly with CTNNB1 mutation status (p = 0.035); all four cases with S45F mutation exhibited strong nuclear expression of β-catenin. S45F mutation was significantly associated with a poor response (all cases; PD) (p = 0.017), whereas the other mutations had no impact on efficacy. The CTNNB1 mutation status was of significant prognostic value for meloxicam treatment in patients with sporadic desmoid tumors.Keywords:
Meloxicam
Surgical oncology
Objective To analyze p 53 gene exon 5 mutations in esophageal cancer (EC) specimens in Xi'an city and Linzhou city.Methods Polymerase chain reaction (PCR) direct sequencing technique was used to detect the alteration of p 53 gene exon 5 for EC specimens from Xi'an city and Linzhou city.Results Mutation rate of p 53 gene exon 5 mutation in Xi'an and Linzhou EC specimens were 14 3%(6/42) and 18 6%(9/43) respectively, which were not significantly different ( P 0 05).Point mutation was the main mutation type.In Xi'an EC specimens, there were six mutation sites including 4-point mutation and 2 base deletions.In Linzhou EC specimens,there were 10 mutation sites,including 9-point mutation and 1 insert mutation.In Xi'an p 53 gene exon 5 mutations were in 126 to 128 bases (4/6),while in Linzhou EC specimens only two had mutations in thiese sites.But these distributions of mutation sites were not significantly different ( P 0 05).Conclusion The p 53 gene exon 5 mutation sites in Xi'an were relatively concentrated;in Linzhou were relatively scattered in different codes,which might be owing to the great variety of risk factors in this district.
Mutation Testing
Cite
Citations (0)
The mutation analysis of alpha-galactosidase A gene was carried out in two families with Fabry disease described by us earlier. In the family P. a new point mutation E341K (a G to A transition at position 10,999 of the gene) was identified. The mutation causes a Glu341Lys substitution in alpha-galactosidase A molecule. Another point mutation was identified in a patient from family N. who had unusual unusually high residual activity of alpha-galactosidase A. The mutation was identified as R112C (a C to T transition at position 5233 of alpha-galactosidase A gene) and it caused the Arg112Cys substitution in the enzyme molecule. This mutation was earlier described in Japanese patient with showed a complete loss of enzyme activity. However, in this case the mutation was combined with another mutation Glu66Gln. The relationship between genetic heterogeneity and clinical manifestation of Fabry disease is discussed.
Alpha (finance)
Cite
Citations (0)
Although during treatment of arthrosis with meloxicam the level of thromboxan A2 decreases, thrombocyte functions are not affected. Meloxicam in therapeutic doses doesn't increase the risk of haemorrhage. Previously it was suspected that co-administration of salicylates with certain other non-steroid antiinflammatory drugs (NSAIDs) will suppress the effect of salicylate. Van Ryn et al have proved that this is not the case with salicylate plus meloxicam therapy. It is hypothesized that meloxicam loosely binds to the cyclooxygenase-1 (COX-1) enzyme and salicylate can easily replace it.
Meloxicam
COX-2 inhibitor
Sodium salicylate
Cite
Citations (0)
Objective: To study the common mutation types and forms of Wilson's Diseases(WD) ATP7B gene.Methods: Peripheral blood DNA were obtained from 30 patients and exons 5,8,12 of ATP7B gene were amplified by PCR and DNA sequencing was applied.Results: The 6 types of mutations found in 30 patients were all point mutation.Among them,5 were identified in exon 8,accounting for 40.00%;1 in exon 12,accounting for 23.33%.No mutation was observed in exon 5.Conclusions: Exons 8 and 12 of ATP7B gene may be the hot points of WD genetic mutation in the population,and Arg778Leu and Arg952Lys may be the mutation point of high frequency.Since no mutation was observed in exon 5,priority should be given to exons 8 and 12 in genetic mutation detection for WD patients.
Cite
Citations (0)
We report the clinical, histochemical, and molecular genetic findings in a patient with progressive mitochondrial cytopathy due to the m.8313G>A point mutation in the mitochondrial tRNA(Lys) (MTTK) gene. The clinical features in this case are severe, including short stature, myopathy, peripheral neuropathy, and osteoporosis, while extensive analysis of maternal relatives indicate that the mutation has arisen de novo and was not maternally inherited. This report of a second case, together with single muscle fiber mutation analysis that shows clear segregation of mutation load with cytochrome c oxidase deficiency, confirms that the mutation is pathologic.
Mitochondrial disease
Cite
Citations (4)
Meloxicam
Crossover study
Cite
Citations (6)
Sickle-cell anemia is caused mutation at molecular point-6 of hemoglobin beta polypeptide chain that would be bisectional significant site shows a deleterious mutation. P53 is a tumor suppresor protein having a curious interaction between molecular point and amino acid composition and is inactivated by several biophysical mutations at its core domain with fall of thermodynamic stability tends to disorder.
Genetic disorder
Cite
Citations (0)
Objective:The major aim of this study is to analyze the point mutation at the codon 54th of MBL in healthy North Huis,and to measure the plasma levels of MBL, and to analyze the association between the mutation frequency and plasma MBL concentrations.Methods:PCR-RFLP was used to detect MBL point mutation.MBL plasma concentrations were measured using MBL Oliger ELISA kit.Results:Frequency of point mutation at the codon 54th of MBL in healthy Huis was 0.15. The plasma MBL concentration was (3.40±2.55)mg/L. There was negative correlation between MBL concentrations and gene mutation frequency in huis(r=-0.67).Conclusion:The relationship between frequency of mutation at codon 54 of MBL gene and the plasma MBL concentrations in healthy Huis is negative correlation.
Mutation frequency
Positive correlation
Cite
Citations (0)
Nonsynonymous substitution
Pseudogene
Synonymous substitution
Silent mutation
Nonsense mutation
Neutral mutation
Cite
Citations (370)
배경: 폐암에서의 EGFR 돌연변이는 폐암을 유발시키는 돌연변이(driver mutation)로 알려져 있다. 대부분의 경우 선암(adenocarcinoma)에서 발견되고 EGFR kinase domain 부분인 exon 18~21 에 변이가 있고 90% 정도가 exon 19 deletion 이나 exon 21 L858R point mutation으로 발현 되는것으로 확인되었다. 하지만 두가지 변이가 동시에 발견된 증례는 아직까지 보고되지 않았다. 소개할 환자는 비소세포폐암 선암종 진단 후 시행한 EGFR mutation 검사상 19 deletion과 21 L858R point mutation 이 동시에 발견되어 이에 대해 보고하는 바이다. 증례: 48세 남자환자로 2015년도 9월 종합검진으로 시행한 가슴전산화단층촬영 상 우상엽 3cm 종괴 관찰되어 추가 검사 진행 위해 입원하였다. 입원 후 시행한 세침조직검사 결과 비소세포폐암 선암종으로 결과 보고되었고 이후 병기 설정 위한 추가 검사 시행하여 뇌, 흉막, 양쪽 폐 침범 소견 관찰되었고 병기4로 진단하였다. 뇌병변에 대해 2015년 10월 13일에서 15일까지 정위적방사선분할치료 시행 하였고 2015년 10월 12일 부터 아파티닙 30mg(지오트립) 경구항암제 사용중이고 이후 시행한 가슴전산화단층촬영상 부분 관해 소견 보이며 현재까지 외래 경과 관찰중이다. 고찰: EGFR mutation 은 TKI 항암제를 사용하는데 지표로 활용되는 염색체 이상 소견으로 exon mutation 이 동시에 두개를 보이는 경우는 현재까지 보고 되지 않았다. Exon 19 deletion 과 exon 21 L858R point mutation 두가지 유전자 변형이 동시에 관찰된 특이 증례에 대해 보고하는 바이다.
Exon trapping
Cite
Citations (0)