Rock Creek Pharmaceuticals Inc. (fka RCPIQ)

[Buddhahead]

Study finds new treatment target for aggressive blood cancer in MNT, Catharine Paddock PhD, February 2015


Excerpt:
"Rsearchers have discovered an interaction between two molecules may contribute to the development of acute myeloid leukemia. They suggest the pathway could be a potential target for treating the aggressive blood cancer and that one of the molecules could serve as a biomarker in personalized therapy of the disease.

"PRL-3 and STAT3 form a regulatory loop that contributes to development of AML
The two molecules identified in the new study - which have been associated with AML before - are the transcription factor STAT3 and the gene PRL-3. A transcription factor is a protein that switches genes on and off by binding to DNA and other proteins.

The Singapore team was the first to report that PRL-3 is overexpressed in 47% of patients with AML. The authors note that higher cellular levels of STAT3 are also found in around 50% of cases of AML.

However, their new study is the first to show the two molecules form a regulatory loop that contributes to the development of AML.

Lead investigator Chng Wee Joo, associate professor at the NUS Yong Loo Lin School of Medicine and deputy director of CSI Singapore, says:

"Earlier studies on PRL-3 have been conducted in other cancers, but only in recent years has attention been turned to the significance of PRL-3 in blood cancer. Previously, the mechanism by which PRL-3 is regulated in AML has also not been fully elucidated."
For their study, the researchers created a core signature for STAT3 by analyzing large datasets in the literature. Using this core signature, they established that STAT3 was significantly enriched in AML patients with high PRL-3 expression.

Using mouse and human cells, they found that STAT3 binds to and promotes the production of PRL-3 in cells, and reducing levels of STAT3 lowered PRL-3 levels and diminished the malignancy of leukemic cells.

They conclude that disruption of this regulatory loop may be a promising way to treat AML and that PRL-3 could be a possible biomarker in personalized therapy for AML patients.

The team is now looking for ways to target the pathway in AML.

In April 2014, Medical News Today also learned about the idea that a gene within a gene drives acute myeloid leukemia. In a study published in Science Signaling, researchers from the US describe how they found it is a smaller gene embedded inside a larger gene already linked to poor survival of AML patients that actually drives progression of the disease."

Article at:
http://www.medicalnewstoday.com/articles/287902.php

My comments: Need help, look at this. Maybe Mullan/Paris/Crawford could help.

Anti-inflammatory activity of anatabine via inhibition of STAT3 phosphorylation.in PubMed, Paris D1, Beaulieu-Abdelahad D, Abdullah L, Bachmeier C, Ait-Ghezala G, Reed J, Verma M, Crawford F, Mullan M., November 2012

Abstract:
"Previous investigations have demonstrated the anti-inflammatory effects of cholinergic agonists, such as nicotine. In the present study, we investigated the potential anti-inflammatory activity of anatabine, a minor tobacco alkaloid also present in plants of the Solanacea family which displays a chemical structural similarity with nicotine. Our data show that anatabine prevents STAT3 and NF?B phosphorylation induced by lipopolysaccharide (LPS) or TNF-a in SH-SY5Y, HEK293, human microglia and human blood mononuclear cells. Using human whole blood, we found that anatabine prevents IL-1ß production induced by LPS. We assessed anatabine's anti-inflammatory activity in vivo using an acute model of inflammation by challenging wild-type mice with LPS. We observed that anatabine reduces pro-inflammatory cytokine production (IL-6, IL-1ß and TNF-a) in the plasma, kidney and spleen of the animals following the injection of LPS and concomitantly opposes STAT3 phosphorylation induced by LPS in the spleen and kidney. We also investigated the impact of anatabine on neuroinflammation using a transgenic mouse model of Alzheimer's disease (Tg APPsw) that displays elevated cytokine levels in the brain. Following a chronic oral treatment with anatabine, a reduction in brain TNF-a and IL-6 levels compared to untreated Tg APPsw mice was observed. Moreover, an increased STAT3 phosphorylation was detected in the brains of Tg APPsw mice compared to wild-type littermates and was inhibited by anatabine treatment. Overall our data show that the anti-inflammatory activity of anatabine in vitro and in vivo is mediated in part via an inhibition of STAT3 phosphorylation."

Article at:
http://www.ncbi.nlm.nih.gov/pubmed/23178521