RRM1 gene can produce a better survival of pancreatic adenocarcinoma

Moffitt Cancer Center researchers have identified a gene that can better predict survival of adenocarcinoma of the pancreas, the fourth leading cause of cancer death in the United States. Researcher Richard Kim, MD, deputy member of the Experimental Therapeutics Program, and colleagues from several other research institutes have conducted a study to define the role of the ribonucleotide reductase M1 (RRM1). The gene encoding the regulatory subunit of ribonucleotide reductase RRM1, the molecular target of gemcitabine, a commonly used chemotherapy in pancreatic cancer.

In the study, published in the January 1 issue of Cancer, the research team studied the therapeutic value prediction RRM1 expression of the chemotherapy drug gemcitabine. They found that patients with adenocarcinoma of the pancreas surgically removed, low RRM1 expression provided a benefit in overall survival with gemcitabine therapy. High expression of RRM1 predicted gemcitabine therapy beneficial not.

"We have already suggested that low expression of RRM1 could predict the success of treatment of gemcitabine," said Kim. "This study was conducted to determine whether RRM1 expression is correlated with better survival in patients treated with gemcitabine."

This retrospective study included 122 patients who had undergone surgery for pancreatic adenocarcinoma 1999-2007. In the subgroup of patients who received gemcitabine treatment, those with low expression of RRM1 longer overall survival and a tendency to progression-free survival. Patients with high expression RRMI who received gemcitabine had a significantly higher overall survival and progression-free survival.

"Our results indicate that the best survival rate after surgical resection, the level of RRM1 expression can be used to select patients treated with gemcitabine and which are not," said Kim.

The authors note that their results were consistent with similar studies on the role of RRM1 plays in chemotherapy for patients with metastatic non-small cell lung cancer, but their findings "should be interpreted with caution" because of their small sample sizes and successful treatment of non-gemcitabine therapy after surgery.

"A validation study must be carried out before the present results can be applied clinically," Kim added.

Source: Moffitt Cancer Center

Man who lost nose to cancer may get new one grown on his arm Read more: http://www.nydailynews.com/news/world/man-lost-nose-cancer-new-article-1.1247336#ixzz2IeJvj8Zf

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Scientists will create two prototypes in case someone drops one.

A man who lost his nose to cancer plans on getting it back by having doctors grow another one on his arm.

British scientists are taking a shot at the groundbreaking procedure by using the man’s bone marrow cells to grow the new nose, which they will then implant under skin in the man’s arm, in a highly controlled laboratory.

Doctors will initially grow two noses “just in case someone drops one,” using molds taken of the patient’s original nose before it was surgically removed, according to Dr. Alex Seifalian of University College London.

For two weeks, two prototypes will be maintained in a bioreactor with the heat set to approximate human body temperature, which helps the cells to multiply.

Simultaneously, Seifalian explained, doctors will insert a small balloon under the skin of one of the patient’s arms and inflate it little by little over weeks to help the skin stretch.

Once the facial features take shape, surgeons will implant one of them in the skin on one of the 53-year-old man’s arms. The unusual process will allow the new nose to grow its own skin and develop a normal blood supply.

"We can make the nose, but we can't make the skin," Seifalian told the Belfast Telegraph.

The made-from-scratch sniffer will remain in the man’s arm for four to six weeks as it continues to develop. After this period, doctors will then sew the nose to the patients face, open the nostrils and implant cells that allow for the secretion of mucus.

The exciting regenerative procedure is unprecedented, according to Seifalian. Doctors at University College London did not respond to a request for comment.

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Drug Is Shown to Help Pancreatic Cancer Cases

Celgene’s drug Abraxane prolonged the lives of patients with advancedpancreatic cancer by almost two months in a clinical trial, researchers reported Tuesday, signifying an advance in treating a notoriously difficult disease but not as big a leap as some doctors and investors had hoped.

“It was not the breakthrough we were anticipating,” said Dr. Andrea Wang-Gillam, an assistant professor and pancreatic cancer specialist at Washington University in St. Louis, who was not involved in the trial.

Still, Dr. Wang-Gillam and others said any progress was welcome against metastatic pancreatic cancer, which has defied most treatments, with patients tending to live only about six months after diagnosis.

Pancreatic cancer is the fourth most common cause of cancer death, with 38,000 Americans expected to die this year, almost as many deaths as from breast cancer, according to the American Cancer Society. Yet there are only 45,000 new cases of pancreatic cancer a year compared with more than 230,000 new breast cancer cases.

“This is a disease that gave oncology a bad name,” said Dr. Robert Mayer, a professor at Harvard and the Dana-Farber Cancer Institute in Boston, who was not involved in the study. Now, he said, Abraxane, as well as another treatment combining four generic drugs, are showing some promise.

In Celgene’s trial, patients who received Abraxane plus gemcitabine, the standard drug for pancreatic cancer, lived a median of 8.5 months, compared with 6.7 months for those who received gemcitabine alone.

At the end of one year, 35 percent of those getting Abraxane were alive, compared with 22 percent of those getting only gemcitabine. After two years, the figures were 9 percent for those getting Abraxane and 4 percent for those who received gemcitabine.

The results of the study, which involved 861 patients, were released by Celgene and by the American Society of Clinincal Oncology in advance of a presentation of the data Friday at the Gastrointestinal Cancers Symposium in San Francisco.

The results were roughly in line with investors’ expectations, according to a recent survey by ISI Group.

Celgene’s stock closed at $99.31 on Tuesday and moved slightly lower in after-hours trading. The study results were released after the close of trading.

Abraxane is a novel form of the widely used cancer drug paclitaxel, also known by the brand name Taxol. In Abraxane, the paclitaxel is bound to albumin, a human protein in tiny particles. That is said to enhance delivery of the drug to tumors and reduce side effects.

Abraxane was approved to treat advanced breast cancer in 2005 and to treat non-small-cell lung cancer in October. Sales in the first nine months of 2012 were $320 million, a small percentage of Celgene’s revenues of $4.1 billion in that period, much of it from the multiple myeloma drug Revlimid.

Abraxane was developed by Abraxis BioScience, which Celgene acquired for $2.9 billion in 2010. Abraxis stockholders also received a security entitling them to additional cash payments if Abraxane won approval for pancreatic cancer. Celgene said Tuesday it would apply for such approval in the first half of this year.

A big impediment to future Abraxane sales in pancreatic cancer could be that its median survival was almost three months less than that of Folfirinox, a combination of four generic cancer drugs.

Results of a clinical trial published in 2011 showed that pancreatic cancer patients getting Folfirinox had a median survival of 11.1 months compared with 6.8 months for those getting gemcitabine.

Experts cautioned that it was difficult to draw conclusions since Abraxane and Folfirinox were not compared directly in the same trial. Nonetheless, doctors are going to make treatment decisions based on the separate results.

Abraxane, which Celgene says will cost $6,000 to $8,000 a month for a pancreatic cancer patients, is likely to be more expensive than Folfirinox. However, Folfirinox is hard to tolerate and requires the patient to wear an infusion pump.

“The simplicity of Abraxane plus gemcitabine may be attractive to physicians and patients,” said Dr. Neal J. Meropol, chief of hematology and oncology at University Hospitals and Case Western Reserve University in Cleveland. Abraxane does cause low white blood cell counts and nerve damage.

How much of an extension of life is meaningful to patients is a matter of some debate, especially with cancer drugs costing thousands of dollars a month.

In 2005 the Food and Drug Administration approved Tarceva, now sold by Roche and Astellas, to treat pancreatic cancer. In a clinical trial, those who got Tarceva plus gemcitabine had a median survival only 12 days longer than those who received a placebo plus gemcitabine.

This article has been revised to reflect the following correction:

Correction: January 22, 2013

An earlier version of this article misstated the specialty of Dr. Andrea Wang-Gillam, an assistant professor at Washington University in St. Louis. She is a specialist in pancreatic cancer, not prostate cancer.

By ANDREW POLLACK

Published: January 22, 2013