Chronic myelogenous leukemia(CML)is a malignancy from bone marrow myeloid stem cells mainly driven by the fusion gene BCR-ABL.In addition to BCR-ABL,other genes including RNF6 are also dysregulated in CML cells.1 RNF6...Chronic myelogenous leukemia(CML)is a malignancy from bone marrow myeloid stem cells mainly driven by the fusion gene BCR-ABL.In addition to BCR-ABL,other genes including RNF6 are also dysregulated in CML cells.1 RNF6,a ubiquitin ligase of the RING family,promotes various cancer cell proliferation,chemoresistance,and tumor growth in vivo by targeting various proteins for ubiquitination and degradation,including SHP1,TLE3,FOXA1,and MAD1.^(2) However,its specific mechanism in CML is not known.展开更多
Uniform amplification of low-input DNA is important for applications across biology,including single-cell genomics,forensic science,and microbial and viral sequencing.However,the requisite biochemical amplification me...Uniform amplification of low-input DNA is important for applications across biology,including single-cell genomics,forensic science,and microbial and viral sequencing.However,the requisite biochemical amplification methods are prone to bias,skewing sequence proportions and obscuring signals relating to copy number.Digital droplet multiple displacement amplification enables uniform amplification but requires expert knowledge of microfluidics to generate monodisperse emulsions.In addition,existing microfluidic methods are tedious and labor intensive for preparing many samples.Here,we introduce rapid-emulsification multiple displacement amplification,a method to generate monodisperse droplets with a hand-held syringe and hierarchical droplet splitter.Although conventional microfluidic devices require >10 min to emulsify a sample,our system requires tens of seconds and yields data of equivalent quality.We demonstrate the approach by using it to accurately measure copy number variation(CNV)in single cancer cells.展开更多
Introduction Colorectal cancer is the third leading cause of cancer-related mortality in the United States[1].Of this group of patients,approximately 39000 cases of rectal cancer were reported in the US in 20151].Trea...Introduction Colorectal cancer is the third leading cause of cancer-related mortality in the United States[1].Of this group of patients,approximately 39000 cases of rectal cancer were reported in the US in 20151].Treatment of rectal cancer truly requires combinatorial therapy with surgery,chemotherapy and radiation(RT),which now comprise the cornerstone of treatment for rectal cancer.展开更多
Background: PD-1 and PD-L1 inhibitors have emerged as promising treatments for patients with head and neck squamous cell carcinoma (HNSCC).Methods: Systematic review and meta-analysis of PD-1 and PD-L1 inhibitors in H...Background: PD-1 and PD-L1 inhibitors have emerged as promising treatments for patients with head and neck squamous cell carcinoma (HNSCC).Methods: Systematic review and meta-analysis of PD-1 and PD-L1 inhibitors in HNSCC. Outcomes: median overall survival (mOS), median progression-free survival (mPFS), Response Evaluation Criteria in Solid Tumors (RECIST) and treatment-related adverse events (TRAEs).Results: Eleven trials reported data on 1088 patients (mean age: 59.9 years, range: 18-90). The total mOS was 7.97 months (range: 6.0-16.5). Mean mPFS for all studies was 2.84 months (range: 1.9-6.5). PD-1 inhibitors had a lower rate of RECIST Progressive Disease than PD-L1 inhibitors (42.61%, 95% confidence interval [CI]: 36.29-49.06 vs. 56.79%, 95% CI: 49.18-64.19,P < 0.001). The rate of TRAEs of any grade (62.7%, 95% CI: 59.8-65.6) did not differ.Conclusions: Meta-analysis shows the efficacy of PD-1 and PD-L1 inhibitors in HNSCC and suggests a possible difference in certain RECIST criterion between PD-1 and PD-L1 inhibitors. Future work to investigate the clinical significance of these findings is warranted.展开更多
基金supported by The National Natural Science Foundation of China(No.81770154,81970194,and 82170176)the National Key Research and Development Program of China(No.2022YFC2705003)+1 种基金Guangzhou Medical University Discipline Construction Funds(Basic Medicine)(China)(No.JCXKJS2022A05)Guangzhou Key Discipline of Medicine(Geriatric Medicine)(China)(No.ZDXK202103).
文摘Chronic myelogenous leukemia(CML)is a malignancy from bone marrow myeloid stem cells mainly driven by the fusion gene BCR-ABL.In addition to BCR-ABL,other genes including RNF6 are also dysregulated in CML cells.1 RNF6,a ubiquitin ligase of the RING family,promotes various cancer cell proliferation,chemoresistance,and tumor growth in vivo by targeting various proteins for ubiquitination and degradation,including SHP1,TLE3,FOXA1,and MAD1.^(2) However,its specific mechanism in CML is not known.
基金We thank Angus Sidore and Freeman Lan for helpful scientific discussions.This work was supported by the UCSF Division of Hematology-Oncology Perkins Philanthropy(PLP)the National Science Foundation CAREER Award(Grant Number DBI-1253293)+2 种基金the National Institutes of Health(NIH)(Grant Numbers HG007233-01,R01-EB019453-01,and DP2-AR068129-01)the Defense Advanced Research Projects Agency Living Foundries Program(Contract Numbers HR0011-12-C-0065,N66001-12-C-4211,and HR0011-12-C-0066)Fold F(x)Program(Contract Number DE-AC02-05CH11231).
文摘Uniform amplification of low-input DNA is important for applications across biology,including single-cell genomics,forensic science,and microbial and viral sequencing.However,the requisite biochemical amplification methods are prone to bias,skewing sequence proportions and obscuring signals relating to copy number.Digital droplet multiple displacement amplification enables uniform amplification but requires expert knowledge of microfluidics to generate monodisperse emulsions.In addition,existing microfluidic methods are tedious and labor intensive for preparing many samples.Here,we introduce rapid-emulsification multiple displacement amplification,a method to generate monodisperse droplets with a hand-held syringe and hierarchical droplet splitter.Although conventional microfluidic devices require >10 min to emulsify a sample,our system requires tens of seconds and yields data of equivalent quality.We demonstrate the approach by using it to accurately measure copy number variation(CNV)in single cancer cells.
文摘Introduction Colorectal cancer is the third leading cause of cancer-related mortality in the United States[1].Of this group of patients,approximately 39000 cases of rectal cancer were reported in the US in 20151].Treatment of rectal cancer truly requires combinatorial therapy with surgery,chemotherapy and radiation(RT),which now comprise the cornerstone of treatment for rectal cancer.
文摘Background: PD-1 and PD-L1 inhibitors have emerged as promising treatments for patients with head and neck squamous cell carcinoma (HNSCC).Methods: Systematic review and meta-analysis of PD-1 and PD-L1 inhibitors in HNSCC. Outcomes: median overall survival (mOS), median progression-free survival (mPFS), Response Evaluation Criteria in Solid Tumors (RECIST) and treatment-related adverse events (TRAEs).Results: Eleven trials reported data on 1088 patients (mean age: 59.9 years, range: 18-90). The total mOS was 7.97 months (range: 6.0-16.5). Mean mPFS for all studies was 2.84 months (range: 1.9-6.5). PD-1 inhibitors had a lower rate of RECIST Progressive Disease than PD-L1 inhibitors (42.61%, 95% confidence interval [CI]: 36.29-49.06 vs. 56.79%, 95% CI: 49.18-64.19,P < 0.001). The rate of TRAEs of any grade (62.7%, 95% CI: 59.8-65.6) did not differ.Conclusions: Meta-analysis shows the efficacy of PD-1 and PD-L1 inhibitors in HNSCC and suggests a possible difference in certain RECIST criterion between PD-1 and PD-L1 inhibitors. Future work to investigate the clinical significance of these findings is warranted.
