106 research outputs found
More Controversy than Ever – Challenges and Promises Towards Personalized Treatment of Gastric Cancer
Dynamic Recruitment of Licensing Factor Cdt1 to Sites of DNA Damage
For genomic integrity to be maintained, the cell cycle and DNA damage responses must be linked. Cdt1, a G1-specific cell-cycle factor, is targeted for proteolysis by the Cul4-Ddb1Cdt2 ubiquitin ligase following DNA damage. Using a laser nanosurgery microscope to generate spatially restricted DNA damage within the living cell nucleus, we show that Cdt1 is recruited onto damaged sites in G1 phase cells, within seconds of DNA damage induction. PCNA, Cdt2, Cul4, DDB1 and p21Cip1 also accumulate rapidly to damaged sites. Cdt1 recruitment is PCNA-dependent, whereas PCNA and Cdt2 recruitment are independent of Cdt1. Fitting of fluorescence recovery after photobleaching profiles to an analytic reaction-diffusion model shows that Cdt1 and p21Cip1 exhibit highly dynamic binding at the site of damage, whereas PCNA appears immobile. Cdt2 exhibits both a rapidly exchanging and an apparently immobile subpopulation. Our data suggest that PCNA provides an immobile binding interface for dynamic Cdt1 interactions at the site of damage, which leads to rapid Cdt1 recruitment to damaged DNA, preceding Cdt1 degradation
Histone degradation in response to DNA damage enhances chromatin dynamics and recombination rates
Hyperfibrinogenemia is associated with lymphatic as well as hematogenous metastasis and worse clinical outcome in T2 gastric cancer
BACKGROUND: Abnormal hemostasis in cancer patients has previously been described, however the correlation between the plasma fibrinogen level and cancer metastasis and prognosis has not been reported in a large-scale clinical study. METHODS: Preoperative plasma fibrinogen levels were retrospectively examined in 405 patients who underwent surgery for advanced gastric cancer. The association of fibrinogen levels with clinical/pathological findings and clinical outcome was evaluated. RESULTS: There was a positive correlation between plasma fibrinogen levels and the depth of invasion (p < 0.05). Hyperfibrinogenemia (>310 mg/dl) was independently associated with lymph node (Odds Ratio; 2.342, P = 0.0032) and liver (Odds Ratio; 2.933, P = 0.0147) metastasis, not with peritoneal metastasis in this series. Patients with hyperfibrinogenemia showed worse clinical outcome in T2 gastric cancer, however, there was no correlation of plasma fibrinogen level with prognosis in T3/T4 gastric cancer. CONCLUSION: Our results might support the idea that hyperfibrinogenemia can augment lymphatic and hematogeneous metastasis of advanced gastric cancer, which is major determinant of the prognosis in T2 gastric cancer. Therefore, in the situation without peritoneal involvement, hyperfibrinogenemia is a useful biomarker to predict the possible metastasis and worse clinical outcome in T2 gastric cancer
Mastectomy vs Breast-Conserving Surgery: An Old Dilemma Comes Again for Early Breast Cancer
Spatial chromosome folding and active transcription drive DNA fragility and formation of oncogenic MLL translocations. Gothe et al.
Western blot and microscopy images of Gothe et al., "Spatial chromosome folding and active transcription drive DNA fragility and formation of oncogenic MLL translocations"
The origins of ALK translocations
Translocations involving the anaplastic lymphoma kinase (ALK) gene locus on chromosome 2p23 were first described in anaplastic large cell lymphoma (ALCL). Although most commonly fused to the nucleophosmin (NPM1) gene on chromosome 5q35, which results in the t(2;5)(p23;q35)/NPM1-ALK translocation, several other ALK translocation partners have meanwhile been identified. Furthermore, apart from ALCL, ALK-involving translocations have been described in other hematopoietic and non-hematopoietic cancers. However, despite a rapid increase in literature on the nature and tissue distribution of ALK-translocations, much less is known about the mechanisms of formation of these translocations. The emergence of translocations has been linked to the transcriptional activity of the respective genome regions, reorganization of the chromatin and activation of the DNA repair machinery. In this review we discuss mechanisms and implications of formation of ALK-translocations
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