Biotechnologists and genetics from the Stanford University School of Medicine have learned to use mini-rings of DNA to force a cancer tumor to manifest itself.

To diagnose cancer, doctors look for traces of specific substances in the blood and urine of patients that release tumors - biomarkers.

For each type of cancer there is an analysis.

Stanford scientists using mini-ring DNA "deceive" the tumor, so that they produce a biomarker and allow themselves to be detected.

Experiments have shown that this approach is effective for different types of cancer. Mini-rings of DNA activate the mechanism that is responsible for the production of secreted embryonic alkaline phosphatase (SEAP). This protein, as the name implies, is normally produced by embryonic tissues, but it should not be present in an adult.

Mini-rings of DNA contain a sequence that allows them to "recognize" malignant cells, as well as the sequence encoding the SEAP protein. Once the minicircle is inside the cancer cell, it is activated and induces the production of SEAP, as if sending a signal.

Researchers write that they introduced into this genetic structure a short DNA sequence called a promoter. Promoters do not code any proteins, but they serve as switches, or more precisely "rheostats", which tell the cell which protein should be synthesized and in what quantities.

Genes in each cell of multicellular organisms are launched by promoters. Although all cells in our body contain the same genes, their activation depends on the specific conditions within a cell at a given time.

Dr. Gambhir and his colleagues placed a DNA promoter inside the mini-ring, connected to the SEAP gene. Normally, it regulates survivin (survivin) gene in adult cells. Survivin is a member of the family of inhibitors of apoptosis (substances that disrupt programmed cell death). The gene of survivin is "included" only in cancer cells, so scientists suggested that mini-rings will activate SEAP secretion only if the patient has cancer.

"The promoter of survivin is used in gene therapy and thoroughly studied. This promoter is activated in many types of cancer cells, including lung cancer, breast cancer, ovarian cancer and others, "says Dr. Gambhir.

For their research, Dr. Gambhir's group injects human melanoma cells into laboratory mice. Normally, the immune system of rodents must attack human cells, cancerous or non-cancerous. But these mice were artificially suppressed immune response, so soon they developed numerous tumors, especially in the lungs. Other mice (control group) were given a drug that did not contain cancer cells.

After about 2 weeks, rodent's blood was tested for secreted embryonic alkaline phosphatase to make sure it was not. Then the researchers injected them into the tail vein of the mini-ring of DNA. Subsequent measurements of the SEAP level were made after 1, 3, 7, 11 and 14 days. Already during the first 48 hours in the blood of rodents this protein was recorded. The signal was amplified 72 hours after the injection, falling to a minimum after 2 weeks.

The level of SEAP varied depending on the size of the tumors. This allows us to hope that this test can be used not only to detect cancer, but also to assess the prevalence of the tumor process.

medbe. en.

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