Recognition of arylmethylidene derivatives of imidazothiazolotriazinones as novel tubulin polymerization inhibitors.

Two series of arylmethylidene derivatives of imidazothiazolotriazinone differing in the structure of the imidazothiazolotriazine fragment were synthesized and their antiproliferative activity and effect on tubulin polymerization were evaluated. Some of the synthesized derivatives showed a significant antiproliferative effect, among which ()-7-(2,4-dichlorobenzylidene)-1,3-diethyl-1,3,4,9-tetrahydroimidazo[4,5-]thiazolo[2,3-][1,2,4]triazine-2,8(3,7)-dione 2n exhibited the highest antiproliferative activity. The GI values of the compound against 56 of the 58 cell lines were 19.

Efficient Selection of Enhancers and Promoters from MIA PaCa-2 Pancreatic Cancer Cells by ChIP-lentiMPRA.

A library of active genome regulatory elements (putative promoters and enhancers) from MIA PaCa-2 pancreatic adenocarcinoma cells was constructed using a specially designed lentiviral vector and a massive parallel reporter assay (ChIP-lentiMPRA). Chromatin immunoprecipitation of the cell genomic DNA by H3K27ac antibodies was used for primary enrichment of the library for regulatory elements. Totally, 11,264 unique genome regions, many of which are capable of enhancing the expression of the CopGFP reporter gene from the minimal CMV promoter, were identified.

Suppression of the Testis-Specific Transcription of the ZBTB32 and ZNF473 Genes in Germ Cell Tumors.

The family of genes containing C2H2 zinc finger domains, which has more than 700 members, is one of the largest in the genome. Of particular interest are C2H2 genes with potential tissue-specific transcription, which determine the functional properties of individual cell types, including those associated with pathological processes. The aim of this work was to identify C2H2 family genes with tissue-specific transcription and analyze changes in their activity during tumor progression.

Chemokine Homeostasis in Healthy Volunteers and during Pancreatic and Colorectal Tumor Growth in Murine Models.

Chemokines are involved in the humoral regulation of body homeostasis. Changes in the blood level of chemokines were found in cancer, atherosclerosis, diabetes, and other systemic diseases. It is essential to distinguish the effects of co-morbid pathologies and cancer on the level of chemokines in the blood.

Combined Effect of Bortezomib and Menadione Sodium Bisulfite on Proteasomes of Tumor Cells: The Dramatic Decrease of Bortezomib Toxicity in a Preclinical Trial.

Tumor growth is associated with elevated proteasome expression and activity. This makes proteasomes a promising target for antitumor drugs. Current antitumor drugs such as bortezomib that inhibit proteasome activity have significant side effects.