Drug composition cytotoxic for pancreatic cancer cells (US)

Disclosed herein are compositions comprising a drug combination that comprises ZD and S3I-201, Das and S3I-201, ZD and AG490, or Das and AG490. The disclosed drug combinations target two or more functional elements such as EGFR or Src and Stat3 or Jaks in pancreatic cancer cells. Also disclosed herein are methods of using the disclosed compositions to cytotoxically affect pancreatic cancer cells and methods of making the disclosed compositions

Inhibitors of Stat3 (US)

Disclosed herein are compounds derived from a chemical structure according to the formula (I) wherein X comprises oxygen or sulfur, R1 comprises a phenyl or naphthyl group, R2 comprises an amide group and R3 comprises a phosphate group. The disclosed compounds demonstrate inhibitory activity against STAT3, a protein found in certain tumor tissues and which promotes cellular overproliferation and resistance to apoptosis. The invention includes compositions containing the disclosed compounds, as well as methods of treatment therewith

Substituted 2-hydroxy-4-(2-(phenylsulfonamido)acetamido)benzoic acid analogs as inhibitors of stat proteins (US)

In one aspect, the invention relates to substituted 2-hydroxy-4-(2-(phenylsulfonamido)acetamido)benzoic acid analogs, derivatives thereof, and related compounds, which are useful as inhibitors of STAT protein activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders of uncontrolled cellular proliferation associated with a STAT protein activity dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention

Compounds that suppress cancer cells and exhibit antitumor activity (US)

The present invention provides compounds S3I-201.1066 (Formula 1) and S3I-201.2096 (Formula 2) as selective Stat3 binding agents that block Stat3 association with cognate receptor pTyr motifs, Stat3 phosphorylation and nuclear translocation, Stat3 transcriptional function, and consequently induced Stat3-specific antitumor cell effects in vitro and antitumor response in vivo

Compounds that suppress cancer cells and exhibit antitumor activity

The present invention provides compounds S3I-201.1066 (Formula 1) and S3I-201.2096 (Formula 2) as selective Stat3 binding agents that block Stat3 association with cognate receptor pTyr motifs, Stat3 phosphorylation and nuclear translocation, Stat3 transcriptional function, and consequently induced Stat3-specific antitumor cell effects in vitro and antitumor response in vivo

Activatable Nanoprobes for Intracellular Drug Delivery

An activatable nanoprobe is provided having a core component and an active agent associated with the core component via a bond configured to be cleaved upon exposure to an endogenous compound

STAT3 inhibitor having anti-cancer activity and methods (US)

A small-molecule Stat3 dimerization inhibitor, S3I-M2001, is described and the dynamics of intracellular processing of activated Stat3 within the context of the biochemical and biological effects of the Stat3 chemical probe inhibitor are elucidated. S3I-M2001 is a newly-identified oxazole-based peptidomimetic of the Stat3 Src Homology (SH) 2 domain-binding phosphotyrosine peptide that selectively disrupts active Stat3:Stat3 dimers. Stat3-dependent malignant transformation, survival, and migration and invasion of mouse and human cancer cells harboring persistently-activated Stat3 were inhibited by S3I-M2001. S3I-M2001 inhibited Stat3-dependent transcriptional regulation of tumor survival genes, such as Bcl-xL. The disclosed compound is useful as a new potential treatment for certain cancers

The Prevalence of Food-borne Pathogenic Organisms in Swine and Pork: A Pilot Survey and Demonstration Project from Production Farm to Dressed Carcasses

This project was unable to demonstrate a protective effect of All in-All out (AIAO) over continuous flow production systems for swine from organisms of food safety interest at the abattoir. It provided valuable information about the ecology of Salmonella spp., Campylobacter spp. and Yersinia enterocolitica on farms and the abattoir. Implanted electronic microchips have been demonstrated as feasible for carcass identification from farm to abattoir cooler. Doubts about predictive values of commonly used detection procedures for on-farm prevalence of these organisms are raised. A new paradigm to explain the nexus of on-farm activities on the microbiologic status of pigs presented to the abattoir is advanced. These studies may substantially refocus farm to abattoir HACCP plans for microbial contamination.

A Functional Nuclear Epidermal Growth Factor Receptor, Src and Stat3 Heteromeric Complex in Pancreatic Cancer Cells

Evidence is presented for the nuclear presence of a functional heteromeric complex of epidermal growth factor (EGFR), Src and the Signal Transducer and Activator of Transcription (Stat)3 proteins in pancreatic cancer cells. Stat3 remains nuclear and associated with Src or EGFR, respectively, upon the siRNA knockdown of EGFR or Src, demonstrating the resistance of the complex to the modulation of EGFR or Src alone. Significantly, chromatin immunoprecipitation (ChIP) analyses reveal the nuclear EGFR, Src and Stat3 complex is bound to the c-Myc promoter. The siRNA knockdown of EGFR or Src, or the pharmacological inhibition of Stat3 activity only marginally suppressed c-Myc expression. By contrast, the concurrent modulation of Stat3 and EGFR, or Stat3 and Src, or EGFR and Src strongly suppressed c-Myc expression, demonstrating that the novel nuclear heteromeric complex intricately regulates the c-Myc gene. The prevalence of the transcriptionally functional EGFR, Src, and Stat3 nuclear complex provides an additional and novel mechanism for supporting the pancreatic cancer phenotype and explains in part the insensitivity of pancreatic cancer cells to the inhibition of EGFR, Src or Stat3 alone

Campylobacter spp. and Yersinia enterocolitica in Growing Pigs in Iowa and North Carolina: A Pilot Study

The prevalence of Campylobacter spp. and Yersinia enterocolitica was determined in cohorts of growing pigs on eight swine farms in Iowa and North Carolina. Approximately 60 pigs from each site were periodically sampled from the nursery to slaughter. Both all in/all out and continuous flow production systems were monitored. Overall, when results from the two states are combined, Campylobacter coli was found in the nursery (90%), grower (92.8%) and finisher (90.9%) stages. At slaughter, C. coli was detected overall on 17.1% of carcasses. For Iowa, 83% of ileocaecal lymph nodes yielded Campylobacter. In contrast, Y. enterocolitica was not found in either rectal or tonsilar swabs or in carcass swabs collected from Iowa hogs. Y. enterocolitica was detected in 8.8% (5 of 57) of North Carolina hogs sampled on one occasion; no isolations were made from carcass swabs at slaughter