Epigenetic alterations are associated with all aspects of cancer, from tumor initiation to cancer progression and metastasis. It is now well understood that both losses and gains of DNA methylation as well as altered chromatin organization contribute significantly to cancer-associated phenotypes. More recently, new sequencing technologies have allowed the identification of driver mutations in epigenetic regulators, providing a mechanistic link between the cancer epigenome and genetic alterations. Oncogenic activating mutations are now known to occur in a number of epigenetic modifiers (i.e. IDH1/2, EZH2, DNMT3A), pinpointing epigenetic pathways that are involved in tumorigenesis. Similarly, investigations into the role of inactivating mutations in chromatin modifiers (i.e. KDM6A, CREBBP/EP300, SMARCB1) implicate many of these genes as tumor suppressors. Intriguingly, a number of neoplasms are defined by a plethora of mutations in epigenetic regulators, including renal, bladder, and adenoid cystic carcinomas. Particularly striking is the discovery of frequent histone H3.3 mutations in pediatric glioma, a particularly aggressive neoplasm that has long remained poorly understood. Cancer epigenetics is a relatively new, promising frontier with much potential for improving cancer outcomes. Already, therapies such as 5-azacytidine and decitabine have proven that targeting epigenetic alterations in cancer can lead to tangible benefits. Understanding how genetic alterations give rise to the cancer epigenome will offer new possibilities for developing better prognostic and therapeutic strategies.
Chromatin ; metabolism ; Chromatin Assembly and Disassembly ; DNA Methylation ; Enhancer of Zeste Homolog 2 Protein ; Epigenesis, Genetic ; Histones ; metabolism ; Humans ; Neoplasms ; genetics ; metabolism ; pathology ; Polycomb Repressive Complex 2 ; genetics ; metabolism

OBJECTIVETo investigate the anti-thrombosis effect and its mechanism of Qingkailing injection (QKL).

METHODSD rats were randomly divided into control group, model group and QKL 2.5, 5.0, 10 groups. QKL were given (i.p.) to rats once a day for successively 4 days. The rats in all groups but control were pretreated with carrageenin (Ca) i.p. at 16 h before the last dose of QKL and followed by intravenous injection of endotoxin ( LPS fom E. coli O111:B4) 50 microg x kg(-1) 30 min after the last dosing of QKL. Thrombosis in rat tails were observed at 24 h after injection of LPS. The number of white blood cells and platelets, serum TNF-alpha, IL-6 level, CD11b/CD18 expression of white blood cells and platelet aggregation were analysed.

RESULTQKL obviously inhibited the LPS/Ca-induced thrombosis as showed a reduced infarction range due to thrombosis in tails. The sera concentration of TNF-alpha and IL-6, expression of CD11b/CD18 in WBC and platelet coagulation rate were reduced after QKL treatment.

CONCLUSIONThe anti-thrombosis action of QKL is associated with inhibition of WBC activation and adherence, reduction of inflammatory factor release and abating of platelet coagulation rate. The anti-thrombosis mechanism of QKL is consistent with its function of clearing away heat-evil and toxic materials.

Animals ; CD11 Antigens ; genetics ; metabolism ; CD18 Antigens ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Fibrinolytic Agents ; administration & dosage ; Gene Expression ; drug effects ; Humans ; Injections, Intraperitoneal ; Interleukin-6 ; blood ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Thrombosis ; drug therapy ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; blood

The pathogeny and the pathogenesis of thrombosis-related diseases are complicated, and family heredity, hypertension, hyperlipoidaemia diabetes and smoking are traditionally considered to be the risky factors. In recent years, various evidences have indicated that infection and inflammation which are defined as virulent heat-evils in traditional Chinese medicine (TCM) are also the risky factors for thrombosis-related diseases. This article analyzed the clinical relativity between virulent heat-evils and thrombosis-related diseases from epidemiology and clinical evidences and the therapeutical practices of TCM on the treatment of thrombosis by using clear away heat-evil and toxic materials principle. Based on the analysis, it can be concluded that dispelling of virulent heat-evils is important for the treatment thrombosis-related diseases. Now the essential of virulent heat-evils associated with thrombosis-related diseases and the nosogenesis of virulent heat-evils are still difficult to be rationally elucidated, and the anti-thrombosis activity of Chinese medicine which functioned as clearing away heat-evil and toxic materials can not be objectively screened and evaluated because no proper thrombosis animal model with virulent heat-evils basis is available at present. Thus, it is necessary to establish a suitable virulent heat-evil-induced thrombosis animal model.
Animals ; Humans ; Medicine, Chinese Traditional ; methods ; Thrombosis ; complications