SSM Gary GlazerWe can surely consider ourselves to be a very fortunate group of people living in this age and era of technological innovations. It now appears that diseases like cancer which are so grave may be detected at an early stage thanks to growing technology. Bearing this topic in mind, a study at the Stanford University School of Medicine has claimed that ultrasound energy apparently given to particular body areas may activate the discharge of biochemical disease markers from tissues, by making those markers more obvious as well as assisting to locate their source.

It was discovered that applying ultrasound energy to a line of tumor cells in culture apparently improved the release of the cells into the culture medium of a telltale substance, or biomarker that might differentiate tumor cells from healthy ones. By means of an animal model, the experts were also able to demonstrate that blood concentrations of that biomarker apparently increased drastically when ultrasound energy was heading for tumor sites but, significantly, not when the ultrasound beam was supposedly concentrated on non-tumor-bearing tissues. Gary Glazer, MD, professor and chair of radiology led the study.

Glazer commented, “Tumors are often not detected until they become sizable enough to cause recognizable symptoms or to be observed themselves as masses on an X-ray or CT scan. By then, the prognosis is much poorer than it might have been had the detection occurred earlier.”

Cancer cells may be known to generate substances which are not usually made by healthy cells and to let go amounts of those telltale cancer-specific biomarkers into the blood. Experts have apparently recognized many biomarkers characteristic of particular tumor types or of diverse cancer stages. This ought to enable comparatively non-invasive premature detection of tumors by examining the blood of the patients for several cancer biomarkers. But only some of them are used for clinical practice. One is PSA, a rather precise early marker of prostate cancer. Another, more accurate biomarker, CEA, is apparently used clinically to identify colon cancer.

Aloma D’Souza, PhD, a research scientist in Glazer’s laboratory and the study’s first author, mentioned, “There are two persistent impediments to the use of biomarkers for early detection of cancer. Their presence in the patient’s blood is at such low levels — particularly in early-stage disease — that finding them amid all the background noise is very difficult. And even when you do find a biomarker, you still don’t know exactly where in the body it came from.”

The circulating levels of some biomarkers may usually be very minute for reliable detection. Glazer explained that the cells which produce them carry multiple copies, up to millions of these substances on their cell membranes or inside, in their cytoplasm. At the right frequencies, ultrasound apparently disturbs the cell’s outer membranes, thus allowing bigger quantities of biomarkers to spill into the bloodstream.

The study experts applied ultrasound to cultured colon-cancer cells and illustrated that it supposedly caused those cells to discharge huge quantities of CEA into the surrounding culture medium. They apparently then optimized the ultrasonic energy level to generate considerable CEA release from the cells without destroying big numbers of them. A significant final clinical objective is apparently to find a patient’s tumor without destroying nearby healthy tissue during the search.

The experts then turned to an animal model in the next round of experiments. They used mice with damaged immune systems, which may accept implants of foreign tissue, as well as human tumors. The CEA levels in the blood of immune-damaged mice were measured to use as a baseline reference. The CEA-producing tumor cells were then implanted into the mice. Once the cells had been implanted to form tumors, ultrasound beams were supposedly aimed at both tumor-bearing and for assessment, tumor-free sites. Ultrasound energy which is believed to aim at tumors considerably raised the mice’s blood levels of CEA as opposed to the levels observed either before tumor cells had been implanted or when the beam was supposedly used in non-cancerous sites in the tumor-bearing animals.

D’Souza remarked, “The application of low-frequency ultrasound to tumor cells caused a significant release of a well-established tumor biomarker into the blood.”

This release took place only when ultrasound was supposedly used directly to the tumor site.

D’Souza quoted, “We think applications of this approach could come very soon. We don’t see significant regulatory impediments to its integration into clinical practice, as ultrasound is widely used already in the clinic. Of course, it will be necessary to optimize the technique for use in humans. And it won’t work for all tumor types — lung or bone-marrow cancers, for example — because ultrasound is impeded by bony structures and air-filled zones in the body. And, while we’ve established proof of principle for a single biomarker, CEA, other biomarkers may prove more difficult to measure this way.”

Sanjiv Gambhir, MD, PhD, professor of radiology, stated, “ This moves us one step closer to solving a key part of the early cancer detection problem, so that we may not have to wait for tumors to grow further in order to detect their presence.”

Glazer is of the opinion that this method might be useful for more than just the treatment of cancer.

This study was published in the journal Proceedings of the National Academy of Sciences.