De Novo Carborane-Containing Macrocyclic Peptides Targeting Human Epidermal Growth Factor Receptor

2019 ◽  
Vol 141 (49) ◽  
pp. 19193-19197 ◽  
Author(s):  
Yizhen Yin ◽  
Nobuaki Ochi ◽  
Timothy W. Craven ◽  
David Baker ◽  
Nagio Takigawa ◽  
...  
1993 ◽  
Vol 292 (2) ◽  
pp. 591-595
Author(s):  
A del Arco ◽  
M Izquierdo

A novel restriction polymorphism, probably due to tissue-specific methylation, has been identified at the human epidermal-growth-factor-receptor (EGF-R) gene. DNA isolated from smooth muscle showed altered EcoRI restriction bands when hybridized with different fragments of the EGF-R cDNA. These bands were absent in brain or leucocyte DNA samples from the same individuals. Three restriction sites, partly resistant to cleavage by EcoRI, were characterized in muscle DNA which were not clustered but instead were scattered along the gene. The flanking sequences of one of these resistant EcoRI sites were determined. This specific EcoRI site was followed by a 3′-guanosine generating a methylatable EcoRI sequence. This suggests that the failure to digest to completion these EcoRI sites was due to modification by methylation. In addition, we noted that EcoRI sites were affected at both alleles, indicating that de novo methylation changes, and not methylation events related to genomic imprinting, would cause the muscle-specific EcoRI pattern. Also abnormal restriction fragments with XbaI were observed in muscle DNA. A large number of unrelated muscle DNA samples have been analysed, and all of them displayed an identical EcoRI polymorphic pattern, suggesting that DNA modification by de novo methylation events could be functionally relevant.


BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e035802
Author(s):  
Qiancheng Hu ◽  
Xin Wang ◽  
Ye Chen ◽  
Xiaofen Li ◽  
Ting Luo ◽  
...  

IntroductionControversy regarding optimum duration of trastuzumab treatment remains in patients with human epidermal growth factor receptor-2 (HER2) positive early breast cancer. The objective of applying network meta-analysis (NMA) is to integrate existing evidence based on direct and indirect comparisons of efficacy and safety, and then to determine the duration of trastuzumab treatments with the greatest impact on therapeutic outcomes in HER2-positive early breast cancers.Methods and analysisElectronic searching of trastuzumab treatments for early breast cancer by titles and abstracts will be conducted for the period from inception to 16 June 2019 in PubMed, Cochrane Library, Embase and ClinicalTrils.gov, as well as the annual meetings of San Antonio Breast Cancer Symposium (SABCS), European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) online archives. The outcomes of interest are overall survival, disease-free survival, acceptability, cardiotoxicities and grade 3 to 4 non-haematological toxicities. Two independent reviewers will screen and extract eligible data based on the inclusion and exclusion criteria, and then assess the risk of bias and evidence quality of individual studies using Cochrane Collaboration’s tool and Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The heterogeneity, transitivity and inconsistency of NMA will be evaluated. In addition, we will perform subgroup and sensitivity analyses to assess the robustness and reliability of findings in our NMA.Ethics and disseminationEthics approval is not required for our NMA. Findings from our NMA will be submitted as peer-reviewed journal manuscripts and international conference reports.Trial registration numberCRD42019139109.


Sign in / Sign up

Export Citation Format

Share Document