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1.
Oncogene ; 35(22): 2824-33, 2016 06 02.
Article in English | MEDLINE | ID: mdl-26387547

ABSTRACT

Cancer stem cells (CSCs) are a promising target for cancer therapy, particularly for metastatic lung cancers, but how CSCs are regulated is largely unknown. We identify two proteins, SLUG (encoded by SNAI2 gene) and SOX9, which are associated with advanced stage lung cancers and are implicated in the regulation of CSCs. Inhibition of either SLUG or SOX9 sufficiently inhibits CSCs in human lung cancer cells and attenuates experimental lung metastasis in a xenograft mouse model. Correlation between SLUG and SOX9 levels was observed remarkably, we therefore sought to explore their mechanistic relationship and regulation. SLUG, beyond its known function as an epithelial-mesenchymal transition transcription factor, was found to regulate SOX9 by controlling its stability via a post-translational modification process. SLUG interacts directly with SOX9 and prevents it from ubiquitin-mediated proteasomal degradation. SLUG expression and binding are necessary for SOX9 promotion of lung CSCs and metastasis in a mouse model. Together, our findings provide a novel mechanistic insight into the regulation of CSCs via SLUG-SOX9 regulatory axis, which represents a potential novel target for CSC therapy that may overcome cancer chemoresistance and relapse.


Subject(s)
Lung Neoplasms/pathology , Neoplastic Stem Cells/pathology , SOX9 Transcription Factor/metabolism , Snail Family Transcription Factors/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Humans , Neoplasm Metastasis , Phenotype , Protein Stability , Proteolysis , Ubiquitination
2.
Bull Exp Biol Med ; 153(1): 54-6, 2012 May.
Article in English | MEDLINE | ID: mdl-22808493

ABSTRACT

Antidiabetic activity of Subetta was revealed on the model of streptozotocin-induced diabetes mellitus in rats. Intragastric administration of this preparation in a dose of 5 ml/kg for 50 days reduced blood glucose levels, urine levels of glucose and ketone bodies, restored glucose tolerance in the oral glucose test, improved general condition and increased the survival rate of animals. The effectiveness of the drug was not inferior to that of rosiglitazone (8 mg/kg).


Subject(s)
Antibodies/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/therapeutic use , Thiazolidinediones/therapeutic use , Animals , Blood Glucose/drug effects , Diabetes Mellitus, Experimental/blood , Male , Rats , Rosiglitazone
3.
Akush Ginekol (Mosk) ; (9): 37-9, 1989 Sep.
Article in Russian | MEDLINE | ID: mdl-2596635

ABSTRACT

The investigation of 220 females with the third trimester of pregnancy revealed that ++cardiotocographic values naturally varied with developing fetal hypotrophy. For instance, hypotrophy, stage I, corresponded, as a rule, to the initial manifestations of fetal chronic disorders whereas hypotrophy, stages II and III, corresponded to the moderate and, occasionally, severe health status.


Subject(s)
Fetal Growth Retardation/physiopathology , Fetal Heart/physiology , Cardiotocography , Female , Humans , Pregnancy , Pregnancy Trimester, Third
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