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Effective Cancer Treatments Follow The Clock

colleagues used mice that genetically lack different components of the body's internal clock. “Knowing the molecular mechanism of internal clock function lets us make some important predictions of how these mice may respond to drug treatment,?said Antoch. “Thus, defects in Clock or Bmal1 genes, which essentially damp the cycles of the internal clock may produce very different effect when compared to defects in Cryptochrome gene, which, in contrast, `jams' the circadian clock at the most active point in its cycle.?/p>

Biological clocks function in the brain as well as lung, liver, heart and skeletal muscles. They operate on a 24-hour, circadian (Latin for "about a day") cycle that governs functions like sleeping and waking, rest and activity, fluid balance, body temperature, cardiac output, oxygen consumption and endocrine gland secretion.

In their experiments, the researchers measured the animals' body weight as an indicator of response to the anti-cancer drug. They discovered that Clock-mutant and Bmal1-knockout mice showed high sensitivity to the drug at any time it was administered ?as if the drug were administered early in the morning or late at night. In contrast, the Cryptochrome knockout mice showed more resistance to the drug at all times than did normal mice.

The researchers then tested whether this effect might be due to differences in the metabolic activation of the anti-cancer drug, but found essentially none. “This was a real surprise, because some of the enzymes involved in activating CY in the liver show circadian rhythms,?said Takahashi. “We thought that the liver might be activating the drug more strongly at some times, or detoxifying it less effectively, or both.?/p>

However, when the researchers analyzed the activity of the knockout animals' immune system B cells, they found evidence that the activity of the Clock and Bmal1 genes determined the cells' sensitivity to CY.

“Thus, this paper gives us specific mechanisti
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Source:Howard Hughes Medical Institute


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