ANN ARBORAn experimental drug combined with the traditional chemotherapy drug cisplatin, when used in mice, destroyed a rare form of salivary gland tumor and prevented a recurrence within 300 days, a University of Michigan study found.

Called adenoid cystic carcinoma, or ACC, this rare cancer affects 3,000-4,000 people annually, and typically arises in the salivary glands. Its usually diagnosed at an advanced stage, is very resistant to therapy, and theres no cure. People may have read about ACC in the news lately, because elite professional runner Gabe Grunewald is currently undergoing her fourth round of treatment since her 2009 ACC diagnosis.

Typically, oncologists treat ACC tumors with surgery and radiation. They rarely use chemotherapy because ACC is extremely slow-growing, and chemotherapy works best on cancers where cells divide rapidly and tumors grow quickly, said Jacques Nr, a U-M professor of dentistry, otolaryngology and biomedical engineering, and principal investigator on the study.

The Nr lab treated ACC tumors with a novel drug called MI-773, and then combined MI-773 with traditional chemotherapy cisplatin. MI-773 prevents a molecular interaction that causes tumor cells to thrive by disarming the critical cancer fighting protein, p53.

Study co-author Shaomeng Wang, U-M professor of medicine, pharmacology and medicinal chemistry, discovered MI-773, which is currently licensed to Sanofi.

Researchers believe that blocking that interaction sensitized ACC cancer cells to cisplatina drug that under normal conditions, wouldnt work. When administered to the mice with ACC tumors, the cisplatin targeted and killed the bulk cells that form the tumor mass, while MI-773 killed the more resistant cancer stem cells that cause tumor recurrence and metastasis.

This drug MI-773 prevents that interaction, so p53 can induce cell death, Nr said. In this study, when researchers activated p53 in mice with salivary gland cancer, the cancer stem cells died.

The key is that in many other types of cancer, p53 is mutated so it cant kill cancer cells, and this mutation renders the MI-773 largely ineffective. However, in most ACC tumors p53 is normal, and Nr said researchers believe this makes these tumors good candidates for this combined therapy.

Researchers performed two different types of experiments to test ACC tumor reduction and recurrence. First, they treated tumors in mice with a combination of MI-773 and cisplatin, and tumors shrank from about the size of an acorn to nearly zero.

In the second experiment, the acorn-sized tumors were surgically removed, and for one month the mice were treated with MI-773 only, with the hope of eliminating the cancer stem cells that fuel recurrence and metastasis.

We did not observe any recurrence in the mice that were treated with this drug after 300 days (about half of mouse life expectancy), and we observed about 62 percent recurrence in the control group that had only the surgery, Nr said. Its our belief that by combining conventional chemotherapy with MI-773, a drug that kills more cancer stem cells, we can have a more effective surgery or ablation.

One limitation of the study is that its known that about half of all ACC tumors recur only after about 10 years, and this observational period was only 300 days.

In a typical metastasis, the cancer cells spread through the blood to other parts of the body. But ACC cancer cells like to move by crawling along nerves, and its common for ACC tumor cells to follow the prominent facial nerves to the brainpicture a mountain climber ascending a ropewhere its often fatal.

Research is still too early-stage to know how humans will respond, and the drug will work primarily in tumors where p53 is normal. If p53 is mutated, which is fairly common in other tumor types, this drug wont work as well, Nr said.

The work was funded by the Adenoid Cystic Carcinoma Research Foundation, U-M and the National Institutes of Health.

The study, Therapeutic Inhibition of the MDM2-p53 interaction prevents recurrence of adenoid cystic carcinomas, appeared earlier this year in the journal Clinical Cancer Research.

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1. What is Stem Cell Therapy?

Stem cell therapy uses a patients own stem cells to treat minor to moderate conditions formally where surgery would be the primary option. Stem cell therapy is an alternative to surgery through an office based procedure. Through advanced technology stem cell therapy is now a quick and easy alternative to surgery.

2. What are stem cells?

Stem cells have the remarkable potential to develop into many different cell types in the body during early life and growth. In addition, in many tissues they serve as of internal repair system, dividing essentially without limit to replenish other cells. When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.

Stem cells are the only cells in the body able to morph into other types of specialized cells. Stem cells are found in many parts of the body but are concentrated in the bone marrow. Through a simple and nearly painless office procedure a small amount of bone marrow can be aspirated from the patient and then concentrated with a centrifuge. The stem cells are then re-injected back into the site of injury or damage. When the patients own stem cells are injected into a damaged joint, they appear to amplify the bodys own natural repair efforts by reducing inflammation, accelerating healing, and preventing scarring and loss of function. It is not only a powerful approach to all stages of arthritis but can be used for treatment of ligament, tendon, cartilage, and even bone problems.

3. Regenerative Growth FactorsStem cells have high natural growth factors that promote healing. These growth factors also naturally decrease inflammation.

4. How is it performed?

Patients stem cells are obtained from their pelvic (hip) bone. The practitioner then concentrates the stem cells over 10 fold in a special centrifuge.

5. How long does it take?This office or surgery center based procedure takes 30 minutes. Patients can leave at the conclusion of the procedure.

6. Does it hurt?

A local anesthetic is used. This results in minimal discomfort.

7. How Well Does it Work?There have been numerous clinical studiesthat show significant and lasting reduction in pain for a variety of injuries. Common injuries include early to advanced arthritis, knee and shoulder pain.

8. How long does it last?

Multiple clinical studieshave shown that when effective, the results last many years.

9. Is there scientific evidence that stem cells work?Yes see the article section

10. What percentage is effective?

85%

11. When can I expect to feel better?

Most patients feel no improvement for at least 3 weeks and possible 6-8 weeks. Once you feel improvement, you will notice continued improvement expanding over 6 months.

12. What is the recovery like after a stem cell procedure?There may be some mild soreness in the joint for up to a week after the injection. Heavy exertion should be avoided during this period. Anti-inflammatory products such as aspirin, motrin, advil, Aleve should be avoided for the first 2 weeks as it can adversely affect the stem cell function. Taking Tylenol is ok.

13. What is the difference between adult stem cells and embryonic stem cells?Adult stem cells are found in mature adult tissues including bone marrow and fat, while embryonic stem cells (ESCs) are not found in the adult human body. ESCs are obtained from donated in vitro fertilizations, which raise many ethical concerns. Because ESCs are not autologous, there is a possibility of immune rejection. Adult stem cells do not raise ethical issues nor pose any risks for immune rejection.

14. Will my body reject the stem cells? Is Stem Cell therapy safe?No, the stem cells come from your own body and are used immediately. Therefore, there is no risk of rejection and virtually no risk of infection.

15. Is this an alternative to a knee replacement?

Stem cells can be highly effective in substantially reducing pain in patients with even advanced arthritis. In addition to the stem cells, bone marrow also contains many powerful growth hormones and anti-inflammatory proteins that will greatly reduce inflammation and promote healthier tissue.

16. Can stem cells grow cartilage in my knee?

Stem cells have been shown in many studies (see studies) to have the power to grow cartilage in certain types of procedures, micro fractures, and tibial osteotomies. The ability for cartilage to form after an injection in the absence of a surgical procedure is still an active area of academic research.

17. Can stem cells help optimize my results from a surgical procedure?

This depends on what type of procedure is done. Microfracture surgery is a common surgical procedure done to restore the cartilage surface in your knee. If your doctor preforms this procedure on you, there are numerous scientific articles (see here) that show a far more robust cartilage healing response when an injection is given post operatively

18. What does it cost?

Most insurance will not cover stem cell procedures. Ask your doctor for payment options.

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