1.Light-inducible CRISPR/Cas9 system for control of gene expression:research advances
Liting LAN ; Xiaoli WEI ; Haitao YAN ; Ruibin SU
Journal of International Pharmaceutical Research 2017;44(3):215-219
Cas9 is a RNA-guided double stranded DNA nuclease that participates in the CRISPR/Cas9 system. Wide-type Cas9 directly silences the expression of target gene by gene splicing. The engineered dCas9 protein with the mutation at D10A and H840A lacks the Cas9' s endonuclease function but keeps its DNA binding activity. dCas9 can activate special genes by fusing with transcription activator. Meanwhile,it can inhibit the gene transcription by directly binding to the target gene and stop gene transcrip?tion. Combination of light sensitive structures and CRISPR can produce light-inducible CRISPR/Cas9 system for control of gene expres?sion. This system is able to activate or inhibit gene expression via the use of controlling blue light(470 nm). In this review,we mainly discuss the development of the light inducible CRISPR/Cas9 system as well as its application in the control of gene expression.
2.Prognostic role of primary tumor burden in extranodal nasal-type NK/T-cell lymphoma
Shunan QI ; Liming XU ; Zhiyong YUAN ; Jianzhong CAO ; Shengmin LAN ; Junxin WU ; Tao WU ; Suyu ZHU ; Liting QIAN ; Xiaorong HOU ; Fuquan ZHANG ; Yujing ZHANG ; Yuan ZHU ; Yong YANG ; Yexiong LI
Chinese Journal of Radiation Oncology 2017;26(5):532-537
Objective There is still a lack of effective clinical prognostic factors for predicting outcomes and guiding treatments in extranodal nasal-type NK/T-cell lymphoma (NKTCL).This study was aimed to investigate the clinical features and prognostic role of primary tumor burden (PTB).Methods A total of 1383 patients were recruited from ten hospitals, including 947 stage Ⅰ patients (68.5%), 326 stage Ⅱ patients (23.6%), and 110 stage Ⅲ-IV patients (8.0%).There were 751 patients (54.3%) presenting with high PTB (H-PTB).The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was conducted for survival difference analysis.Meanwhile, a multivariate analysis was performed using the Cox regression model.Results H-PTB was associated with high invasive potential, high frequency of B symptoms, advanced stage, regional lymph node involvement, lactate dehydrogenase elevation, and poor performance status.The patients with H-PTB had significantly lower 5-year overall survival (OS) and progression-free survival (PFS) rates than those with low PTB (L-PTB)(OS:50.2% vs.72.1%, P=0.000;PFS:41.8% vs.62.5, P=0.000).PTB was an independent prognostic factor for both OS (HR=1.851) and PFS (HR=1.755) according to the Cox multivariate analysis.Moreover, H-PTB was associated with significantly lower locoregional control (LRC) in early-stage NKTCL, and the 5-year LRC rate was 71.6% in patients with H-PTB and 84.3% in those with L-PTB (P=0.000).Conclusions H-PTB is associated with multiple adverse clinical features in NKTCL, and it is an independent indicator for poor outcomes and LRC.H-PTB can be used as a reliable indicator for risk stratification and treatment decision.
3.Prognostic value of anemia in patients with extranodal nasal-type NK/T cell lymphoma:A multi-center study from CLROG
Hui FANG ; Suyu ZHU ; Liming XU ; Peiguo WANG ; Tao WU ; Liting QIAN ; Fuquan ZHANG ; Xiaorong HOU ; Shunan QI ; Yong YANG ; Jing JIN ; Yujing ZHANG ; Yuan ZHU ; Jianzhong CAO ; Shengmin LAN ; Junxin WU ; Yexiong LI
Chinese Journal of Radiation Oncology 2018;27(2):155-160
Objective To evaluate the prognostic value of anemia in patients diagnosed with extranodal nasal-type natural killer (NK)/T cell lymphoma (NKTCL).Methods Clinical data of 1 225 NKTCL patients receiving the first course of treatment from 10 medical institutions in China were retrospectively analyzed.According to the diagnostic criteria in China,anemia was defined as the hemoglobin (Hb) level< 120 g/L for the male and< 110 g/L for the female from the sea-level area.The severity of anemia was classified into the extremely severe anemia (Hb ≤ 30 g/L),severe anemia (31-60 g/L),moderate anemia (61-90 g/L) and mild anemia (>90 g/L).Results Among 1 225 patients,199(16.2%) were complicated with anemia,who had more adverse prognostic factors compared with their counterparts without anemia.Among NKTCL patients with anemia,the proportion of patients with stage Ⅱ-ⅣV,a median age> anemia,Eastern Cooperative Oncology Group (ECOG) score of 2-4 and NK/T-cell lymphoma prognostic index (NKTCLPI) ≥ 2 was relatively high.Patients with anemia obtained worse clinical prognosis than those without anemia.The 5-year overall survival (OS) and progression-free survival (PFS) in NKTCL patients with anemia were calculated as 49.4% and 35.4%,significantly lower compared with 63.3% and 56.0% in their counterparts without anemia (both P<0.01).Single factor analysis demonstrated that anemia,age,ECOG score,group B symptom,lactate dehydrogenase,primary tumor site,primary tumor invasion and staging were the prognostic factors of OS and PFS.Multivariate analysis revealed that anemia was still the independent prognostic factor.Conclusions Anemia is not common in patients with NKTCL and these patients obtain poor clinical prognosis.Anemia is an independent prognostic factor for patients with NKTCL.