Mutational Analysis of Triple-Negative Breast Cancer Using Targeted Kinome Sequencing

PurposeTriple-negative breast cancer (TNBC) does not have defined therapeutic targets and is currently treated with chemotherapy only. Kinase dysregulation triggers cancer cell proliferation and metastasis and is a crucial therapeutic target for cancer. In this study, targeted kinome sequencing of TNBC tumors was performed to assess the association between kinome gene alterations and disease outcomes in TNBC.MethodsA kinome gene panel consisting of 612 genes was used for the targeted sequencing of 166 TNBC samples and matched normal tissues. Analyses of the significantly mutated genes were performed. Genomic differences between Asian and non-Asian patients with TNBC were evaluated using two Asian TNBC datasets (from Seoul National University Hospital [SNUH] and Fudan University Shanghai Cancer Center [FUSCC]) and three non-Asian TNBC datasets (The Cancer Genome Atlas [TCGA], METABRIC, and Gustave Roussy). The prognostic value of kinome gene mutations was evaluated using tumor mutational burden (TMB) and oncogenic pathway analyses. Mutational profiles from the TCGA were used for validation.ResultsThe significantly mutated genes included TP53 (60% of patients), PIK3CA (21%), BRCA2 (8%), and ATM (8%). Compared with data from non-Asian public databases, the mutation rates of PIK3CA p.H1047R/Q were significantly higher in the SNUH cohort (p = 0.003, 0.048, and 0.032, respectively). This was verified using the FUSCC dataset (p = 0.003, 0.078, and 0.05, respectively). The TMB-high group showed a trend toward longer progression-free survival in our cohort and the TCGA TNBC cohort (p = 0.041 and 0.195, respectively). Kinome gene alterations in the Wnt pathway in patients with TNBC were associated with poor survival in both datasets (p = 0.002 and 0.003, respectively).ConclusionComprehensive analyses of kinome gene alterations in TNBC revealed genomic alterations that offer therapeutic targets and should help identify high-risk patients more precisely in future studies.     

Factors associated with long-term smoking relapse in those who succeeded in smoking cessation using regional smoking cessation programs

It is known that approximately 10% of successful quitters relapse annually. This study aimed to investigate the factors related to long-term smoking relapse in individuals who succeeded in maintaining smoking cessation for 6 months after attending a regional smoking cessation program.This study enrolled 943 individuals registered for the regional smoking cessation program at the Busan Smoking Cessation Center in 2018–2019 who maintained smoking cessation for 6 months. A survey was conducted using a smartphone link or through phone calls, and the data for 305 participants who finally completed the survey were analyzed. The questionnaire addressed individual, inter-individual, organizational, and community-level factors related to smoking relapse. Multivariate logistic regression analysis was performed to evaluate the factors associated with smoking relapse by period. The Cox proportional hazard regression model was used for the factors associated with smoking relapse for the entire period.The smoking relapse rate at the time of the survey was 25.4%. In the analysis of smoking relapse by period, relapse was associated with the belief that smoking relieves stress, the number of single-person households, and poor subjective health status. In the analysis of smoking relapse during the entire period, we observed a significant association with the belief that smoking relieves stress (hazard ratio [HR]: 2.65, 95% confidence interval [CI]: 1.52–4.61), single-person households (HR: 1.95, 95% CI: 1.16–3.26), and high levels of emotional stress (HR: 1.72, 95% CI: 1.04–2.85).Long-term follow-up is necessary to prevent smoking relapse in single-person households, individuals who believe that smoking relieves stress, and those experiencing high levels of subjective emotional stress. Interventional therapies for stress relief and awareness improvement in smokers need to be developed.     

Serial blood concentration of polyethoxylated tallow amine and clinical presentations in acute herbicide poisoning

<正>1Department of Emergency Medicine, Chungnam National University Hospital, Daejeon 35015, South Korea2Department of Emergency Medicine, College of Medicine, Chungnam National University, Daejeon 35015, South Korea3Forensic Toxicology Division, National Forensic Service, Daejeon 34054, South Korea4Department of Emergency Medicine, Chungbuk National University Hospital, Cheongju 28644, South Korea Corresponding Author:Wonjoon Jeong, Email:gardenjun@hanmail.net     

Microsurgical anatomy of the facial nerve

The facial nerve connections and pathways from the cortex to the brainstem are intricate and complicated. The extra‐axial part of the facial nerve leaves the lateral part of the pontomedullary sulcus and enters the temporal bone through the internal acoustic meatus. In the temporal bone, the facial nerve branches into fibers innervating the glands and tongue. After it emerges from the temporal bone it supplies various facial muscles. It contains a motor, general sensory, special sensory, and autonomic components. The physician needs comprehensive knowledge of the anatomy and courses of the facial nerve to diagnose and treat lesions and diseases of it so that surgical complications due to facial nerve injury can be avoided. This review describes the microsurgical anatomy of the facial nerve and illustrates its anatomy in relation to the surrounding bone, connective, and neurovascular structures.     

Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis

Background  

Curcumin (diferuloylmethane), the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of Curcuma longa. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy.     

Response to pretransplant hypomethylating agents influences the outcome of allogeneic hematopoietic stem cell transplantation in adults with myelodysplastic syndromes

This study describes a retrospective analysis on the transplant outcome of 56 consecutive patients with myelodysplastic syndrome (MDS) according to their response to hypomethylating agents (HMA). While 2‐yr disease‐free survival (DFS) of patients who transformed to acute myeloid leukemia (n = 12) was 25%, that of the remaining patients with MDS according to response to HMA was 73.1%, 68.1%, 50.0%, and 20.8% in G‐COR (group of continuous response, n = 19), G‐NoC (group of no change, n = 15), G‐LOR (group of loss of response, n = 6), and G‐DP (group of disease progression, n = 4), respectively. When dichotomized as G‐COR/G‐NoC versus G‐LOR/G‐DP, significantly different 2‐yr DFS (71.0% vs. 33.3%; P = 0.004) and relapse (14.1% vs. 46.7%; P = 0.016) were demonstrated. On multivariate analysis, G‐LOR/G‐DP [hazard ratio (HR), 3.91; P = 0.008] and poor karyotype at transplantation (HR, 2.69; P = 0.017) were the significant predictors for poor DFS, as G‐LOR/G‐DP was for relapse (HR, 6.28; P = 0.011). DFS was significantly poor in patients with any of the two predictors in all MDS (81.5% vs. 34.9%; P = 0.001) or higher‐risk MDS (HrMDS) at the time of HMA (80.7% vs. 29.2%; P = 0.005). G‐COR showed a trend of better DFS compared with G‐NoC among HrMDS (74.6% vs. 36.5%; P = 0.090). These results implicate the significance of response to HMA on hematopoietic stem cell transplantation (HSCT) outcomes and support the need for future study to verify the suggested strategy of proceeding to transplantation before LOR or DP, especially for HrMDS.