A new study, now published in the journal Cell, suggests that the \nway in which the human body processes nitrogen may be key to finding new\n ways of detecting and destroying cancer.<\/p>\n\n\n\n
Nitrogen is a gas that is vital for all organisms. Both plants and animals need it in order to make proteins.<\/p>\n\n\n\n
When our body processes nitrogen, it generates a substance called \nurea as waste; the body later eliminates this substance through urine.<\/p>\n\n\n\n
This metabolizing process is called the urea cycle, and it takes place in the liver.<\/p>\n\n\n\n
New research suggests that dysregulations in the urea cycle could be a\n marker of cancer. The new study was led by Dr. Ayelet Erez, from the \nWeizmann Institute of Science in Rehovot, Israel.<\/p>\n\n\n\n
Studying urea dysregulations and tumors
\nDr. Erez and colleagues altered the genetic expression of urea cycle \nenzymes in the colon cancer tumors of rodents and compared their urea \nlevels with those of control mice.<\/p>\n\n\n\n
The mice whose urea cycle had been interfered with had lower blood \nlevels of urea and higher levels of a substance called pyrimidine in \ntheir urine.<\/p>\n\n\n\n
The scientists also examined the medical records of 100 children who \nhad been diagnosed with cancer at the Tel Aviv Sourasky Medical Center.<\/p>\n\n\n\n
\u201cWe found that on the day of their admission to the hospital,\u201d \nexplains the lead researcher, \u201cchildren with cancer had significantly \ndecreased urea levels in their blood, compared with documented levels of\n urea in healthy children of the same age.\u201d<\/p>\n\n\n\n
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\nFinally, the researchers also analyzed large genomic sets in search of \nDNA mutations that could indicate disruptions in the urea cycle.<\/p>\n\n\n\n
They found mutations in DNA, RNA, and proteins, which indicates an \nexcess of pyrimidine. This is produced through the synthesis of nitrogen\n and can, in turn, promote the growth of cancer cells.<\/p>\n\n\n\n
Overall, the findings suggest that dysfunctions in the urea cycle may be a good indicator of cancer.<\/p>\n\n\n\n
\u201cStandard laboratory tests check for high levels of urea in blood, \nbut we are now showing that low levels can also signal a problem,\u201d says \nDr. Erez. \u201cCancerous cells don\u2019t waste anything, they make use of as \nmuch nitrogen as possible instead of disposing of it in the form of \nurea, as do normal cells.\u201d<\/p>\n\n\n\n
Making tumors vulnerable to immunotherapy
\nAs the researchers explain, high levels of pyrimidine represent both \ngood news and bad. The bad news is that it could make the cancer spread \nfaster and more aggressively, but the good news is that the mutations \nthat are related to excessive pyrimidine could make cancer cells more \nvulnerable to an attack from the immune system.<\/p>\n\n\n\n
Therefore, malignancies characterized by a dysregulated urea cycle could be destroyed more easily with immunotherapy.<\/p>\n\n\n\n
To test this hypothesis, Dr. Erez and colleagues examined melanoma \ntumors and found that the tumors that had dysregulated urea cycles \nresponded better to immunotherapy. Dr. Erez and colleagues conclude:<\/p>\n\n\n\n
\u201cTaken together, our findings demonstrate that [urea cycle \ndysregulation] is a common feature of tumors that profoundly affects \ncarcinogenesis, mutagenesis, and immunotherapy response.\u201d<\/p>\n\n\n\n
Moreover, say the researchers, the results could lead to better tools not only for diagnosing cancer, but also for treating it.<\/p>\n\n\n\n
\u201cYet another possibility worth exploring,\u201d Dr. Erez says, \u201cis whether\n genetic manipulation of the tumor to induce such dysregulation prior to\n immunotherapy can increase the therapy\u2019s effectiveness.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"
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