PHILADELPHIA INTERNATIONAL MEDICINE NEWS BUREAU
Contact: Leonard N. Karp
lkarp@philadelphiamedicine.com
215-735-3989
For Immediate Release:
In this month’s issue:
1. Penn Study Looks at Weight Gain as a Result of Diabetes Treatment
2. Fox Chase Offering Free TRAM Flap for Breast Reconstruction after Mastectomy
3. Combining Two Types of Radiation Therapy Better for Treating Brain Cancer
Penn Study Looks at Weight Gain as a Result of Diabetes Treatment
Philadelphia - If obesity is the leading cause of type II diabetes, then why do thiazolidinediones (TZDs), the only available drugs that treat this form of diabetes, actually cause more weight gain?
Researchers at the University of Pennsylvania Medical Center, a member of the Philadelphia International Medicine network of hospitals and medical schools, have addressed the fundamental workings of TZDs (also known as glitazones or under brand names such as Actos® and Avandia®), and provide a potential new target for further study.
Their research describes how TZDs trigger the creation of glycerol kinase, an enzyme that causes fat cells to store fatty acids faster than it produces them.
"It is what researchers call a 'futile' cycle. Just as fat cells release their larder of fatty acids, glycerol kinase causes the fat cells to put them back in storage," said Mitchell A. Lazar, MD, PhD, chief of the division of endocrinology, diabetes, and metabolism and director of the Penn Diabetes Center.
"The glycerol kinase is packing the pantry faster than fat cells can pull the cans off of the shelves. The net influx of fatty acids into fat tissue contributes to reduced fatty acids in the bloodstream that, in turn, leads to increased sensitivity to insulin."
Type II, or adult-onset diabetes, occurs as cells lose the ability to respond to insulin, a hormone that allows cells to absorb sugar for fuel. The disease affects millions, and has become an epidemic in the industrialized world.
According to Lazar, two big mysteries remain concerning type II diabetes: how cells become insulin resistant and how TZDs cause them to lose resistance to insulin. By studying how the drug works, the researchers have uncovered a fundamental clue that may allow the development of better therapies.
"Right now, our findings suggest that weight gain is an inherent part of how TZDs function and diabetics should bear in mind the role of a healthy diet in combination with drug therapy," said Lazar. "TZDs actually lower insulin requirements in diabetics, and this is likely to be beneficial in terms of the risk of hypertension and heart disease associated with diabetes."
Despite their beneficial qualities, it seems that TZDs have little respect for medical textbooks. "According to conventional medical knowledge, fat cells do not produce glycerol kinase for precisely the reason that helps TZDs to be effective," said Lazar.
Fatty acids are stored in fat cells as triglycerides (TGs). When the body senses that it needs fuel, such as what happens when diabetic cells cannot absorb blood sugar, fat cells breakdown TGs to produce glycerol, which travels to the liver to make the sugar glucose, and fatty acids, which muscles use as an emergency fuel source.
TZDs, however, reverse this process as it happens. When the drug binds to a receptor in fat cells called PPARgamma, TZD causes the cells to uncharacteristically produce glycerol kinases. These enzymes then recombine glycerol and fatty acids into TGs. They also open the cell's door to trap passing fatty acids, which lowers the amount of fatty acids in the bloodstream.
In addition, researchers have found that TZDs may also alter the chemical signals produced by fat cells, which may prove beneficial in producing the next generation of anti-diabetes drugs.
"We have come to understand that fat cells are more than just storage bins for excess fats," said Lazar. "They produce hormones and actively regulate how our bodies process and use fats. Future drug discovery may depend on the role of fat itself."
Fox Chase Offering Free TRAM Flap for Breast Reconstruction after Mastectomy
Fox Chase Cancer Center is now offering the most advanced breast reconstruction procedure for women who have had a mastectomy for breast cancer. The procedure, called a free tissue transfer or free TRAM flap, uses a woman's own tissue and fat from her stomach (tummy tuck) to build a more natural-looking and natural-feeling breast.
"The restoration of the breast is an integral part of treating women for breast cancer," explained Neal S. Topham, MD, chief of plastic and reconstructive surgery at Fox Chase Cancer Center. "The goal with breast reconstruction surgery is to match the appearance of the remaining breast in size, shape and texture. The free TRAM procedure is a delicate surgery that yields excellent results and allows better symmetry using the patients' own tissue."
Despite tremendous advances in the treatment of breast cancer leading to breast-sparing procedures, nearly one-third of breast cancer patients still require a mastectomy. Many of these patients choose to have breast reconstruction.
"Many women are able to have breast reconstruction at the same time as their mastectomy, but they may opt to have the surgery later," said Topham. "Fox Chase Cancer Center can now provide women with the entire spectrum of reconstructive options, including implants, the TRAM flap procedure, free tissue transfer or a combination of these procedures. Each woman's circumstances will be different and choosing a procedure that is right for her is critical to a positive outcome."
Procedures using a woman's own tissue from her abdomen to reconstruct a breast are called TRAM (transverse rectus abdominus myocutaneous) flap procedures. For the free TRAM flap or free tissue transfer, the surgeon removes an island of fat, skin and muscle from the abdomen, shapes it into a breast and attaches it at the location of the mastectomy.
The procedure requires microsurgery -- surgery under a microscope -- to attach the artery and veins in the flap to blood vessels located in the chest wall. For some patients, the surgeon is able to modify the procedure to remove only skin and fat from the abdomen, preserving the abdominal muscle (perforator flap).
The TRAM flap procedure requires the removal of skin and fat from the stomach. One end of the abdominal muscle is cut while the uncut area allows permanent blood flow. The skin, fat and muscle are tunneled under the skin to the breast area, which may cause some bulging. After the flap has been transferred, either by tunneling or by the free TRAM procedure, the tissue is molded to resemble the shape and size of the opposite breast instead of the typical round shape of an implant.
The free tissue transfer allows the surgeon greater freedom to shape the new breast, while the pedicle TRAM procedure is limited by the connected muscle. "The benefit of the free TRAM over a pedicle TRAM flap procedure is that the breast will have a better shape, especially for larger busted women," explained Topham. "The free TRAM eliminates the bulge created by the muscle tunneled to the breast for the pedicle TRAM procedure. For some free TRAM cases, we may be able to remove only the skin and fat, leaving the abdominal muscle completely intact."
Combining Two Types of Radiation Therapy Better for Treating Brain Cancer
Adding stereotactic radiosurgery after whole brain radiation therapy helps certain patients with cancer that has spread to the brain live longer, says a new study conducted by researchers at the Thomas Jefferson University Hospital, a member of Philadelphia International Medicine.
In as many as one-third of all patients with lung and breast cancers, the disease spreads to the brain, leaving few good options. The disease causes neurological problems, and many patients live only about four months. Chemotherapy has been relatively ineffective in shrinking tumors and improving quality of life.
"It's a substantial problem and progress in their management has been quite slow," says Walter Curran, Jr., MD, professor and chair of radiation oncology at Jefferson Medical College and clinical director of Jefferson's Kimmel Cancer Center.
The standard treatment is two to three weeks of whole brain radiation, which helps improve neurological function and quality of life. Between 1996 and 2001, researchers at Jefferson Medical College and elsewhere randomly assigned 333 patients to receive either whole brain radiation therapy alone, or whole brain radiation therapy followed by stereotactic radiosurgery. The latter, used to treat benign tumors, entails delivering radiation to specific areas of the brain while sparing healthy tissue.
They found that patients with a single brain metastases who received radiosurgery immediately after whole brain radiation lived on average one to two months longer. Those with two or three brain metastases who had "good performance status" had some improvement in survival as well, says Curran. Those without a "good activity level" didn't do as well.
His team presented its results October 7, 2002, at the American Society for Therapeutic Radiology and Oncology's Annual Meeting in New Orleans.
"It's the first time any trial using non-operative therapy has shown a survival advantage in these patients," Curran, who is chairman of the Radiation Therapy Oncology Group, a federally funded cancer clinical trials group which carries out multi-disciplinary research nationwide and which conducted the study.
"We had no evidence whether or not using it at the time of diagnosis would be beneficial. The only time we've shown survival advantage before was surgical removal. Now, for the first time, something that is not an operation makes a difference.
"Intuitively, it makes sense," he says. "Because this has been such a difficult group for which to change survival, we found it gratifying that we could show a positive result." The researchers hope to be able to add medications to the treatment program to further improve survival.
Philadelphia International Medicine is an organization that provides medical and patient support services to international patients. It also provides continuing medical education and health care training and education to international physicians, administrators and other practitioners. As the international department of several Philadelphia-area hospitals, international patients gain access to physicians and hospitals rated among the best in the world through one telephone call to PIM. You can reach PIM by calling 1-215-735-3575; fax, 1-215-790-1267; or e-mail, physicians@philadelphiamedicine.com. You can find out more about PIM through its Website at www.philadelphiamedicine.com.