This week… cancers, brains, and fruit flies.
Combinatorial therapy to fight melanoma: Malignant melanomas are aggressive cancers that are highly resistant to chemotherapy, possibly due to high levels of Bcl-2 family anti-cell death proteins. Although the small molecule inhibitor, ABT-737, is effective against Bcl-2 family proteins in other cancers, it is not very effective in melanoma cases. The reason may be due to overexpression of another protein, Mcl-1, which confers resistance to ABT-737. When Dr. Victor Tron’s group at Queen’s University combined ABT-737 treatment with inhibitions of Mcl-1 by way of siRNA knockdown, the cancer cells lost their resistance and underwent cell death. These findings, appearing this week in PloS One , suggest that the combination of ABT-737 and Mcl-1 knockdown represents a promising, new treatment strategy for malignant melanoma.
Understanding Stat3 in Breast Cancer: Elevated Stat3 levels in breast cancer patients often correlate with poor clinical outcome. To understand how Stat3 may influence cancer progression, a Stat3 knockout mouse was combined with a mouse expressing the mutant form of the breast cancer gene, ErbB2, and predisposed to develop breast tumours. What the researchers at McGill University found was that without Stat3, breast cancer still developed but the malignancy of the mammary tumours decreased significantly with fewer animals having metastatic lesions in the lung. Genetic profiling of the tumours showed that without Stat3, angiogenic and inflammatory responses, which often play an important role in the metastatic process, were blunted. Remember, last week I noted an article on Par6 and TGFb in breast cancer metastasis.
This recent study, hot off the press in Cancer Research, was led by Dr. William Muller, one the early pioneers in using transgenic mouse technology.
Gene expression differences in suicide brains: This is the first study to perform global gene expression analysis on the brains of suicide cases to try to broaden the scope of suicide research to other neurotransmitter systems. The serotonergic system is well studied as the primary area of the brain involved in suicides but there are likely other contributing factors. Dr. Turecki’s research team at McGill University performed microarray expression studies on a number of brain tissue samples from the cortical and subcortical regions to identify potentially new molecular pathways involved in depression and suicide. Their results revealed a number of alterations including genes involved in synaptic neurotransmission, namely upregulation of glutamatergic (excitatory) and GABAergic (inhibitory) related genes in suicide brains. This report in PLoS One should open the research field into exploring alternate treatment methods and better understanding the development of suicide and depression.
Male hormone discovery: A new male-specific pheromone was identified on fruit flies. When the researchers transferred some of the compound onto female fruit flies, the male flies were suddenly uninterested. How did they identify this pheromone? They exposed a fruit fly to a laser in a MALDI-type mass spectrometer instrument where ions are ejected into the instrument and analyzed. Some previously unidentified compounds were discovered including this hormone. The research was conducted at the University of Toronto Mississauga by Joel Levine and Jocelyn Millar and appears in this week’s Current Biology.