Chemotherapy Plus Synthetic Compound Provides Potent Anti-Tumor Effect in Pancreatic Cancers

Human pancreatic cancer cells dramatically regress when treated with chemotherapy in combination with a synthetic compound that mimics the action of a naturally occurring "death-promoting" protein found in cells, researchers at UT Southwestern Medical Center have found.

Researchers led by Dr. Rolf Brekken have shown in mice that pancreatic cancer cells dramatically regress when treated with chemotherapy in combination with a synthetic "death-promoting" compound. 

The research, conducted in mice, appears in the March 23 issue of Cancer Research and could lead to more effective therapies for pancreatic and possibly other cancers, the researchers said.
"This compound enhanced the efficacy of chemotherapy and improved survival in multiple animal models of pancreatic cancer," said Dr. Rolf Brekken, associate professor of surgery and pharmacology and the study's senior author. "We now have multiple lines of evidence in animals showing that this combination is having a potent effect on pancreatic cancer, which is a devastating disease."
In this study, Dr. Brekken and his team transplanted human pancreatic tumors into mice, then allowed the tumors to grow to a significant size. They then administered a synthetic compound called JP1201 in combination with gemcitabine, a chemotherapeutic drug that is considered the standard of care for patients with pancreatic cancer. They found that the drug combination caused regression of the tumors.
"There was a 50 percent regression in tumor size during a two-week treatment of the mice," Dr. Brekken said. "We also looked at survival groups of the animals, which is often depressing in human therapeutic studies for pancreatic cancer because virtually nothing works. We found not only significant decrease in tumor size, but meaningful prolongation of life with the drug combination."
The drug combination was also effective in an aggressive model of spontaneous pancreatic cancer in mice.
The compound JP1201 was created in 2004 by UT Southwestern researchers to mimic the action of a protein called Smac. The researchers discovered Smac in 2000 and found that this protein plays a key role in the normal self-destruction process present in every cell.
Cell death, or apoptosis, is activated when a cell needs to be terminated, such as when a cell is defective or is no longer needed for normal growth and development. In cancer cells, this self-destruct mechanism is faulty and lead to breaks in the cell-death cascade of events. The synthetic Smac, or Smac mimetic, developed at UT Southwestern inhibits these breaks, allowing the cell to die.
"In essence, we're inhibiting an inhibitor," Dr. Brekken said. "And we're allowing the apoptotic cascade to kick off, resulting in the death of cancer cells."
UT Southwestern researchers are using Smac mimetics in breast and lung cancer research, as well. Dr. Brekken said the next step is to develop a compound based on JP1201 that can be tested in humans in clinical trials.
Other UT Southwestern researchers involved in the study included lead author Dr. Sean Dineen, surgery resident; Dr. Christina Roland, surgery resident; Rachel Greer, student research assistant in the Nancy B. and Jake L. Hamon Center for Therapeutic Oncology Research; Juliet Carbon, senior research associate in surgery and in the Hamon Center; Jason Toombs, research assistant in surgery and in the Hamon Center; Dr. Puja Gupta, a pediatric hematology/oncology fellow; Dr. Noelle Williams, associate professor of biochemistry; and Dr. John Minna, director of the W.A. "Tex" and Deborah Moncrief Jr. Center for Cancer Genetics and of the Hamon Center.
The research was supported by Susan G. Komen for the Cure and Joyant Pharmaceuticals, a Dallas-based company and UT Southwestern spinoff that is developing medical applications of Smac-mimetic compounds.

Experts say U.S. doctors overtesting, overtreating

Too much cancer screening, too many heart tests, too many cesarean sections. A spate of recent reports suggest that too many Americans — maybe even President Obama — are being overtreated.

Is it doctors practicing defensive medicine? Or are patients so accustomed to a culture of medical technology that they insist on extensive tests and treatments?

A combination of both is at work, but now new evidence and guidelines are recommending a step back and more thorough doctor-patient conversations about risks and benefits.

As a medical journal editorial said this week about Obama's recent checkup, Americans including the commander in chief need to realize that "more care is not necessarily better care."

Obama's exam included prostate-cancer screening and a virtual colonoscopy. The PSA test for prostate cancer is not routinely recommended for any age and colon screening is not routinely recommended for patients younger than 50. Obama is 48. (PSA stands for prostate-specific antigen screening).

Earlier colon-cancer screening is sometimes recommended for high-risk groups — which a White House spokesman noted includes blacks. Doctors disagree on whether a virtual colonoscopy is the best method. But it's less invasive than traditional colonoscopies and doesn't require sedation — or the possible temporary transfer of presidential power, the White House said.

The colon exam exposed him to radiation "while likely providing no benefit to his care," Dr. Rita Redberg, editor of Archives of Internal Medicine, wrote in an online editorial. "People have come to equate tests with good care and prevention," Redberg, a cardiologist with the University of California, San Francisco, said in an interview Thursday. "Prevention is all the things your mother told you — eat right, exercise, get enough sleep, don't smoke — and we've made it into getting a new test."

This week alone, a New England Journal of Medicine study suggested that too many patients are getting angiograms — invasive imaging tests for heart disease — who don't really need them; and specialists convened by the National Institutes of Health said doctors are too often demanding repeat cesarean deliveries for pregnant women after a first C-section.

Experts dispute how much routine cancer screening saves lives.

Not all doctors and advocacy groups agree with the criticism of screening. Many argue that it can improve survival chances and that saving even a few lives is worth the cost of routinely testing tens of thousands of people.

While some patients clearly do benefit from screening, others clearly do not, said Dr. Richard Wender, former president of the American Cancer Society.

These include very old patients, who may unrealistically fear cancer and demand a screening test, when their risks are far higher of dying from something else, Wender said.

Doctors also often order tests or procedures to protect themselves against lawsuits — so-called defensive medicine — and also because the fee-for-service system compensates them for it, said Dr. Gilbert Welch, a Dartmouth University internist and health-outcomes researcher.

While many patients also demand routine tests, they're often bolstered by advertisements, medical information online — and by doctors, too, Welch said.

The new guidance from the cancer society last week on PSA testing, echoing others' advice on mammograms, is for doctors and patients to thoroughly discuss testing, including a patient's individual disease risks, general pros and cons of testing and possible harms it may cause.

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Medical Identity Theft

     The latest addition to the world of fraud , medical identity theft. You might be wondering what really is " Medical Identity Theft" . It is in simple words , usage of ones health cards by some other person without the knowledge of its real owner. The owner of the card may come to the realization of the fraud only when his service provoder sent him bills for thousands of dollars for some surgeries that he never underwent.
                                     The irony is that most of the fraud are done by family members or close family friends. So the number of cases reported will be very rare. The hospital authorities also didn't check much details once they are provided with health cards , that also is a reason for this fraud to develop.

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