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Oxygen Microbubbles May Increase Efficacy of Radiation Therapy

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Some abnormal masses of tissues do not have cysts or hollow cavities that contain liquid. These are solid tumors that can be benign or malignant which usually occur in the bones, muscles, and organs. Solid tumors have a unique trait which is having a natural resistance to both chemotherapy and radiation therapy. But the researchers at Thomas Jefferson University developed a new technique to circumvent that resistance.

Typically, solid tumors are classified as carcinomas and sarcomas which are often treated with surgery. Carcinomas form in the cells of the skin, glands, and organ linings called epithelial cells. An example of carcinoma is the adrenocortical carcinoma that forms in the adrenal glands. On the other hand, sarcomas are tumors that form in the blood vessels, bones, fat tissues, ligaments, lymph vessels, muscles tissues, and tendons. One example of sarcoma is the rhabdomyosarcoma that forms in muscles. About 30 percent of cancer cases in children are solid tumors, while brain tumors are the most common of solid tumors in children.

Solid tumors are often treated with surgery, chemical therapy, and radiation therapy; however, they have a natural resistance to the latter two treatment options. Radiation therapy works by creating oxygen and other free radicals in tumors. But the resistance caused by tumor hypoxia lowers the oxygen levels in the tissues. Low oxygen levels in tumor tissues produce fewer oxygen radicals that make both chemotherapy and radiotherapy ineffective.

According to a study published in 2007, the ineffectiveness of the treatments is mostly due to the free radical mechanism of oxygen in stimulating cells to convert radiation. In another study in 2015, pathological hypoxia affects cell quiescence or state of inactivity. The effects of hypoxia in tumors can regulate signaling pathways, allowing the abnormal cells to change metabolism and state of activity.

But the new technique can work around that problem by delivering oxygen directly to the tumors. The researchers used microbubbles filled with oxygen to instill the chalcogen in the tumors. The microbubbles can be popped by using beams from an ultrasound machine when they have reached the desired target.

"Finding a way to reverse oxygen deficiency in tumors has been a goal in radiation therapy for over 50 years. We've demonstrated here that oxygen microbubbles flush tumors with the gas, and make radiation therapy significantly more effective in animal models,” said Dr. John Eisenbrey, the senior author of the study and an assistant professor of radiology at Thomas Jefferson’s.

The research team tested the new technique in mice models. They administered the microbubbles into the bloodstream of mice and popped them to deliver oxygen to the tumor, which increased the oxygen levels in the abnormal mass. The effect of the oxygenation increased the vulnerability of the tumor to radiation therapy by 300 percent, while increasing the survival rate of the mice by nearly two times. Mice treated with oxygen microbubbles survived for 76 days while the mice treated with nitrogen microbubbles survived for only 46 days.

“The very act of bursting these microbubbles within the tumor tissue seems to change the local physiology of the tumor and make cells generally more permeable to oxygen and potentially to chemotherapy as well. We think this is a promising approach to test in patients to amplify the effects of radiation therapy,” said Dr. Eisenbrey.

Dr. Eisenbrey and the rest of the team are currently using a similar technique in an in-human clinical trial of microbubbles. The researchers used the tiny bubbles to enhance the radiation treatment against liver cancer. But the microbubbles do not contain oxygen, instead, these were used to disrupt cancer to provide therapeutic benefit over radiotherapy.

Oxygen treatment is not new in cancer therapy. In fact, oxygen has been used to improve the condition of cancer patients. The technique is called hyperbaric oxygen treatment that involves giving extra oxygen to the patient. Normally, healthy tissues damaged by some cancer treatments heal over time, but the blood vessels in the treated area have likely lost the ability to supply blood in healing areas.

HBO helps reverse the damage done by certain cancer treatments in healthy tissues. In HBO, the oxygen is 100 percent pure that dissolves quickly and uses high pressure to increase oxygen intake, which puts more oxygen into the bloodstream to quicken the healing rate. Side effects of HBO include painful sinuses or facial pain because of changes in the pressure, blurred vision, lightheadedness, fatigue, and ear problems. In very rare occasions, prolonged exposure to HBO can damage the lungs. Aside from reducing the growth of some cancer types and improving chemotherapy, HBO can also be used to treat the following conditions:

- Decompression or the bends.

- Severe carbon monoxide poisoning.

- Gangrene and some infections.

- Diabetic foot ulcers.

- Delayed wound healing after surgery.

[메디컬리포트=​Ralph Chen 기자]

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