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Articles by S. J. Lee
Total Records ( 2 ) for S. J. Lee
  J. Y Byun , C. H Yoon , S An , I. C Park , C. M Kang , M. J Kim and S. J. Lee
 

To prevent the development of malignancies, mammalian cells activate disposal programs, such as programmed cell death, in response to deregulated oncogene expression. However, the molecular basis for regulation of cellular disposal machinery in response to activated oncogenes is unclear at present. In this study, we show that upregulation of the autophagy-related protein, Atg5, is critically required for the oncogenic H-ras-induced autophagic cell death and that Rac1/mitogen-activated kinase kinase (MKK) 7/c-Jun N-terminal kinase (JNK) signals upregulation of Atg5. Overexpression of H-rasV12 induced marked autophagic vacuole formation and cell death in normal fibroblasts, which remained unaffected by a caspase inhibitor. Pretreatment with Bafilomycin A1, an autophagy inhibitor, completely attenuated H-rasV12-induced cell death as well as autophagic vacuole formation. Selective production of Atg5 was observed in cells overexpressing H-rasV12, and small interfering RNA (siRNA) targeting of Atg5 clearly inhibited autophagic cell death. Interestingly, inhibition of JNK or c-Jun by specific siRNA suppressed Atg5 upregulation and autophagic cell death. Moreover, inhibition of MKK7, but not MKK4, effectively attenuated H-rasV12-induced JNK activation. In addition, ectopic expression of RacN17 or Rac1-siRNA effectively inhibited MKK7–JNK activation, Atg5 upregulation and autophagic cell death. These data support the notion that upregulation of Atg5 is required for the oncogenic H-ras-induced autophagic cell death in normal fibroblasts and that activation of Rac1/MKK7/JNK-signaling pathway leads to upregulation of Atg5 in response to oncogenic H-ras. Our findings suggest that in cells acquiring deregulated oncogene expression, oncogenic stress triggers autophagic cell death, which protects cells against malignant progression.

  M. S Kowalsky , I. J Kremenic , K. F Orishimo , M. P McHugh , S. J Nicholas and S. J. Lee
 

Background: Recently, some have suggested that the acromioclavicular articulation confers stability to the construct after coracoclavicular ligament reconstruction for acromioclavicular joint separation. Therefore, it has been suggested that distal clavicle excision should not be performed in this context to protect the graft during healing.

Hypothesis: Sectioning the acromioclavicular ligaments would significantly increase in situ forces of a coracoclavicular ligament graft, whereas performing a distal clavicle resection would not further increase in situ graft forces.

Design: Controlled laboratory study.

Methods: A simulated coracoclavicular reconstruction was performed on 5 cadaveric shoulders. Static loads of 80 N and 210 N were applied directly to the clavicle in 5 directions: anterior, anterosuperior, superior, posterosuperior, and posterior. The in situ graft force was measured using a force transducer under 3 testing conditions: (1) intact acromioclavicular ligaments, (2) sectioned acromioclavicular ligaments, and (3) distal clavicle excision.

Results: For both magnitudes of load, in all directions, in situ graft force with intact acromioclavicular ligaments was significantly less than that with sectioned acromioclavicular ligaments (P < .001). Distal clavicle excision did not further increase the in situ graft forces with load applied to the clavicle in an anterior, anterosuperior, or superior direction. However, in situ graft forces were increased with distal clavicle excision when the clavicle was loaded with 210 N in the posterosuperior direction (60.4 ± 6.3 N vs 52.5 ± 7.1 N; P = .048) and tended to be increased with posterior loading of the clavicle (71.8 ± 6.2 N vs 53.1 ± 8.8 N; P = .125).

Conclusion: Intact acromioclavicular ligaments protect the coracoclavicular reconstruction by decreasing the in situ graft force. The slight increase in the in situ graft force only in the posterosuperior and posterior direction after distal clavicle excision suggests only a marginal protective role of the acromioclavicular articulation. Further, the peak graft forces observed represent only a small fraction of the ultimate failure strength of the graft.

Clinical Relevance: Distal clavicle excision can perhaps be safely performed in the context of coracoclavicular ligament reconstruction without subjecting the graft to detrimental in situ force. Although the acromioclavicular articulation serves only a marginal role in protecting the coracoclavicular ligament graft, reconstruction of the acromioclavicular ligaments may serve an important role in decreasing in situ graft force during healing.

 
 
 
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