Publications (2)5.17 Total impact
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ABSTRACT: To investigate the impact of KIT and PDGFRA gene mutations on the prognosis of gastrointestinal stromal tumors (GIST). Tumor tissue from 184 patients with primary GIST was submitted to mutational analysis of exons 9, 11, 13, and 17 of the KIT gene and exons 12 and 18 of the PDGFRA gene. Clinical and pathological parameters were analyzed and correlated to the risk of recurrence and disease-free survival (DFS). The authors found that somatic mutations were detected in 162 tumors (88.0%). Age, clinical stage, mitotic count, and tumor size were of prognostic relevance on both univariate and multivariate analysis. Five-year DFS was 41.9%. While the presence of a KIT or PDGFRA mutation per se was not associated with tumor recurrence and/or disease-free survival, exon 11 deletion and hemizygous mutation status were both independent factors highly predictive for poor survival. The authors conclude that KIT exon 11 deletions and somatic loss of the wild-type KIT identified patients with poor prognosis. Age, clinical stage, tumor size, and mitotic count were standard clinicopathologic features that significantly influenced the prognosis. Mutation type of the mitogen receptor c-kit has a potential for predicting the course of the disease and might contribute to management individualization of GIST patients.
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ABSTRACT: To investigate the molecular events involved in liver regeneration following subtotal hepatectomy (SH) as previous studies have largely focused on partial hepatectomy (PH). Male Wistar rats were subjected to 70% PH or 90% SH, respectively, and sacrificed at different times after surgery. Untreated and sham-operated animals served as controls. Serum and liver samples were obtained to investigate liver function, apoptosis (TUNEL assay) and transcription factors (NF-kappaB, Stat3; ELISA) or cytokines (HGF, TNF-alpha, IL-6, TGF-alpha, TGF-beta; quantitative RT PCR) involved in liver regeneration. Serum levels of ALT and AST in animals with 70% PH differed significantly from sham-operated and control animals. We found that the peak concentration 12 h after surgery returned to control levels 7 d after surgery. LDH was increased only at 12 h after 70% PH compared to sham. Bilirubin showed no differences between the sham and 70% resection. After PH, early NF-kappaB activation was detected 12 h after surgery (313.21 +/- 17.22 ng/mL), while there was no activation after SH (125.22 +/- 44.36 ng/mL) compared to controls (111.43 +/- 32.68 ng/mL) at this time point. In SH, however, NF-kappaB activation was delayed until 24 h (475.56 +/- 144.29 ng/mL). Stat3 activation was similar in both groups. These findings correlated with suppressed and delayed induction of regenerative genes after SH (i.e. TNF-alpha 24 h postoperatively: 2375 +/- 1220 in 70% and 88 +/- 31 in 90%; IL-6 12 h postoperatively: 2547 +/- 441 in 70% and 173 +/- 82 in 90%). TUNEL staining revealed elevated apoptosis rates in SH (0.44% at 24 h; 0.63% at 7 d) compared to PH (0.27% at 24 h; 0.15% at 7 d). The molecular events involved in liver regeneration are significantly influenced by the extent of resection as SH leads to suppression and delay of liver regeneration compared to PH, which is associated with delayed activation of NF-kappaB and suppression of proregenerative cytokines.