ABSTRACT
CASE: A 47-year-old Japanese woman with a medical history of xanthoma disseminatum (XD) presented with posterior neck pain and abnormal gait without a history of trauma. Imaging studies revealed odontoid process thinning resulting in its fracture due to XD involvement in the atlantoaxial joint and subsequent cervical myelopathy. Posterior C1-C2 fusion surgery improved the patient's symptoms. An XD lesion around the odontoid process was confirmed intraoperatively. CONCLUSION: We report cervical myelopathy caused by XD involvement in the C1-C2 joint, showing that early fusion surgery is critical for treating pathological fractures in patients with XD.
Subject(s)
Histiocytosis, Non-Langerhans-Cell , Odontoid Process , Spinal Cord Diseases , Spinal Fractures , Spinal Fusion , Female , Histiocytosis, Non-Langerhans-Cell/complications , Humans , Middle Aged , Odontoid Process/injuries , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/etiology , Spinal Cord Diseases/surgery , Spinal Fractures/complications , Spinal Fractures/diagnostic imaging , Spinal Fusion/adverse effectsABSTRACT
Gefitinib (GEF), an inhibitor for EGFR tyrosine kinase, potently induces autophagy in non-small cell lung cancer (NSCLC) cell lines such as PC-9 cells expressing constitutively activated EGFR kinase by EGFR gene mutation as well as A549 and H226 cells with wild-type EGFR. Unexpectedly, GEF-induced autophagy was also observed in non-NSCLC cells such as murine embryonic fibroblasts (MEF) and leukemia cell lines K562 and HL-60 without EGFR expression. Knockout of EGFR gene in A549 cells by CRISPR/Cas9 system still exhibited autophagy induction after treatment with GEF, indicating that the autophagy induction by GEF is not mediated through inhibiting EGFR kinase activity. Combined treatment with GEF and clarithromycin (CAM), a macrolide antibiotic having the effect of inhibiting autophagy flux, enhances the cytotoxic effect in NSCLC cell lines, although treatment with CAM alone exhibits no cytotoxicity. GEF treatment induced up-regulation of endoplasmic reticulum (ER)-stress related genes such as CHOP/GADD153 and GRP78. Knockdown of CHOP in PC-9 cells and Chop-knockout MEF both exhibited less sensitivity to GEF than controls. Addition of CAM in culture medium resulted in further pronounced GEF-induced ER stress loading, while CAM alone exhibited no effect. These data suggest that GEF-induced autophagy functions as cytoprotective and indicates the potential therapeutic possibility of using CAM for GEF therapy. Furthermore, it is suggested that the intracellular signaling for autophagy initiation in response to GEF can be completely dissociated from EGFR, but unknown target molecule(s) of GEF for autophagy induction might exist.
