ABSTRACT
Cancer cell heterogeneity is a serious problem in the control of tumor progression because it can cause chemoresistance and metastasis. Heterogeneity can be generated by various mechanisms, including genetic evolution of cancer cells, cancer stem cells (CSCs), and niche heterogeneity. Because the genetic heterogeneity of CSCs has been poorly characterized, the genetic mutation status of CSCs was examined using Exome-Seq and RNA-Seq data of liver cancer.Here we show that different surface markers for liver cancer stem cells (LCSCs) showed a unique propensity for genetic mutations. Cluster of differentiation 133 (CD133)-positive cells showed frequent mutations in the IRF2, BAP1, and ERBB3 genes. However, leucine-rich repeat-containing G protein-coupled receptor 5-positive cells showed frequent mutations in the CTNNB1, RELN, and ROBO1 genes. In addition, some genetic mutations were frequently observed irrespective of the surface markers for LCSCs. BAP1 mutations was frequently observed in CD133-, CD24-, CD13-, CD90-, epithelial cell adhesion molecule-, or keratin 19-positive LCSCs. ASXL2, ERBB3, IRF2, TLX3, CPS1, and NFATC2 mutations were observed in more than three types of LCSCs, suggesting that common mechanisms for the development of these LCSCs. The present study provides genetic heterogeneity depending on the surface markers for LCSCs. The genetic heterogeneity of LCSCs should be considered in the development of LCSC-targeting therapeutics.
ABSTRACT
OBJECTIVE: We performed the surgery using titanium double cylindrical cage for anterior cervical discectomy and interbody fusion in various degenerative cervical diseases. We compared the clinical results and radiologic results in cervical anterior disectomy. Method: From October 2007 to October 2008, 19 patients diagnosed with degenerative disease underwent anterior cervical disectomy and interbody fusion. The postsurgical clinical results were analyzed retrospectively by classifying them into four levels based on Odom's criteria(excellent, good, fair, and poor) after a more than 6-month follow-up period. RESULTS: In all cases, a single segment was involved, and surgery was performed for 19 segments. The C5-C6 inter-vertebral disc was the most commonly affected(9 cases). The clinical outcome was excellent, good, and fair in 5(26.3 %), 10(52.6%), and 4(21.0%) cases, respectively. An excellent or good outcome was considered as a successful result, showing an approximately 78.9% cure rate. No patient had aggravated symptoms compared with their preoperative status. CONCLUSION: Relatively satisfactory clinical and radiographic results were obtained with double cylindrical cages. The surgical method is relatively simple, allows good synostosis, and prevents many complications associated with autografting. It is also less traumatic to the spinal cord during cage insertion. Therefore, double cylindrical cages are generally more recommended for treating cervical spondylosis accompanied with flat cages.