Pic Of Day

Posted by rob on October 27, 2004 under Uncategorized | Be the First to Comment

This image taken Tuesday, Oct. 26, 2004, by the spacecraft Cassini, is one of the closest ever of Saturn’s hazy moon Titan. The image was captured by the spacecraft’s imaging science subsystem as it flew by Titan. At its closest, Cassini was 1,200 kilometers (745 miles) above the moon, 300 times closer than during its first flyby on July 3, 2004.

Orphan Drug Designation Granted to Kosan’s 17-AAG for the Treatment of Chronic Myelogenous Leukemia (CML)

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Orphan Drug Designation Granted to Kosan’s 17-AAG for the Treatment of Chronic Myelogenous Leukemia (CML)
Tuesday October 26, 7:30 am ET

HAYWARD, Calif., Oct. 26 /PRNewswire-FirstCall/ — Kosan Biosciences Incorporated (Nasdaq: KOSNNews) today announced that the U.S. Food and Drug Administration has granted its anticancer compound 17-allylamino-17-demethoxy- geldanamycin, or 17-AAG, an analog of the polyketide geldanamycin, orphan drug status for the treatment of Chronic Myelogenous Leukemia (CML). 17-AAG is being evaluated for the treatment of multiple cancer indications in Phase II, Phase I, and Phase Ib clinical trials, including a Phase Ib trial with Gleevec(TM) as a combination therapy in CML. These trials are being conducted in collaboration with the National Cancer Institute (NCI) under a Cooperative Research and Development Agreement (CRADA) between Kosan and the NCI Cancer Therapy Evaluation Program (CTEP).

“This is the second orphan drug designation granted in the U.S. to Kosan and the NCI, and is a significant achievement for the collaborative geldanamycin analog clinical program,” said Robert G. Johnson, Jr., M.D., Ph.D., Executive Vice President, Development and Chief Medical Officer, Kosan Biosciences. “This designation strengthens Kosan’s position in this highly visible area of clinical development and can afford important marketing advantages to Kosan in the future.”

17-AAG inhibits Hsp90 (heat shock protein 90), a protein chaperone that binds to signaling proteins, known as “client proteins.” These client proteins include a “who’s who” list of cancer-relevant targets such as mutated p53, Bcr-Abl, Her2, Akt, Raf-1, B-Raf, and others. When 17-AAG binds to Hsp90, it disrupts the Hsp90-client protein complexes, leading to degradation of the client proteins.

Chronic myelogenous leukemia, or CML, often referred to as chronic myeloid leukemia is a cancer of the blood system in which too many white blood cells (WBCs) are produced in the bone marrow. CML has three distinct phases. The chronic phase can be insidious in onset and last several years. This is followed by an accelerated phase, accompanied by a more rapid growth rate of the malignant WBCs. Finally, CML patients enter into a “blast crisis” stage associated with a rapid rate of cell growth and a survival of only a few months on average. The American Cancer Society estimates that 4,300 new cases of chronic myelogenous leukemia will be diagnosed this year in the United States. CML usually occurs in people in their 40s and beyond, although it can occur in younger patients.

About Orphan Drug Designation

Orphan drug designation is granted by the U.S. Food and Drug Administration to products that treat rare diseases or conditions that affect fewer than 200,000 people in the United States. The designation provides eligibility for a special seven-year period of market exclusivity after marketing approval, potential tax credits for research, grant funding for research and development, possibly reduced filing fees for marketing applications, and assistance with the review of clinical trial protocols.

About Kosan

Kosan Biosciences has two first-in-class anticancer agents in Phase II clinical trials. KOS-862 (Epothilone D) is in Phase II and Phase Ib clinical trials and is partnered with Roche in a global development and commercialization agreement. 17-AAG, Kosan’s lead geldanamycin analog, is in Phase II and Phase Ib clinical trials, and DMAG, its second-generation geldanamycin analog, is in Phase I. Both compounds are being developed in collaboration with the National Cancer Institute. Kosan’s proprietary formulation of 17-AAG, designated KOS-953, is in Phase I. 17-AAG and DMAG are polyketide inhibitors of Hsp90 and interrupt several biological processes implicated in cancer cell growth and survival. Kosan’s focus is on an important class of natural products known as polyketides. Polyketides are a class of natural products that have yielded numerous important pharmaceuticals for the treatment of cancer, infectious diseases, high cholesterol, transplant rejection and other diseases. Kosan applies its expertise and proprietary technologies to generate polyketide analogs and increase the production yields of polyketides, resulting in a robust pipeline of potentially significant products for cancer, as well as for infectious disease and other therapeutic areas. For additional information on Kosan Biosciences, please visit the Company’s website at www.kosan.com.

This press release contains “forward-looking” statements, including statements relating to the ongoing and further development and potential efficacy and commercialization of 17-AAG and KOS-953 in the treatment of cancer. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. There are a number of important factors that could cause the results of Kosan to differ materially from those indicated by these forward-looking statements, including, among others, risks related to the clinical advancement of 17-AAG, KOS-953 and other geldanamycin analogs and Kosan’s dependence on the collaboration with the NCI and other risks detailed from time to time in the Company’s SEC reports, including its Quarterly Report on Form 10-Q for the quarter ended June 30, 2004, and other periodic filings with the SEC. Kosan does not undertake any obligation to update forward-looking statements.

 


Source: Kosan Biosciences Incorporated

http://biz.yahoo.com/prnews/041026/sftu015_1.html

St. John’s Wort Thwarts Cancer Drug

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Herbal Supplement Cuts Effectiveness of Cancer-Fighting Drug Gleevec


Oct. 26, 2004 — The herbal supplement St. John’s Wort reduces the effectiveness of the cancer-fighting drug Gleevec, according to researchers from the University of Buffalo.

“Based on the results of this study, St. John’s Wort should be avoided in patients treated with [Gleevec], if possible,” write the researchers, who included Patrick Smith, PharmD.

Gleevec is used to treat a type of cancer called chronic myeloid leukemia (CML). As the first drug to specifically target cancer cells, it was considered a breakthrough medication and was quickly approved by the U.S. Food and Drug Administration (FDA) in 2001.

Currently, Gleevec is only approved to treat CML. However, other studies have suggested that it might have potential in combating other kinds of cancer.

Gleevec differs from chemotherapy in several respects. First, it’s taken orally, rather than intravenously. Second, the pills are spread over years, whereas chemotherapy is typically conducted in concentrated time periods. In addition, it zeroes in on cancer cells only, rather than killing all the cells in an affected area.

St. John’s Wort, on the other hand, is not a cancer treatment. Instead, it’s a popular supplement that has been used for years for medicinal purposes including mood elevation and mild-to-moderate depression.

While there is some evidence that St. John’s Wort works to treat mild and moderate depression, it lacks effect in treating major depression. However, St. John’s wort can interact with certain drugs, and these interactions can be dangerous.

Previous Cautions

Many of the so-called “natural substances” can have harmful effects. If taken in large quantities or if taken with another drug that interferes with its availability, these natural substances can have negative health consequences.

Several studies have shown that St. John’s Wort conflicts with prescription medications. In 2002, a Dutch study showed that St. John’s Wort interfered with and limited the effectiveness of the cancer-fighting medication irinotecan.

The FDA has warned in the past that St. John’s Wort could interact with a host of medications reducing their effectiveness, including those taken for HIV infection (indinavar), heart disease (high blood pressure calcium channel blockers such as diltiazam), seizure, cancer, organ transplant rejection (cyclosporine), and pregnancy (birth control pills).

Next: Latest Findings With St. John’s Wort

Latest Findings

Smith’s study, which is scheduled to appear in the November issue of the journal Pharmacotherapy, tested St. John’s Wort’s effects on Gleevec in 10 healthy adults.

The 18-day study was conducted in two phases. First, participants took 400 milligrams of Gleevec with a light meal after an overnight fast, then provided periodic blood samples for the next 48 hours.

Next, participants kept taking Gleevec in the same manner, along with 300 milligrams of St. John’s Wort three times daily for 15 days.

Gleevec’s effects were “significantly altered” by St. John’s Wort, say the researchers. Gleevec’s blood levels were diminished by 32%-42%.

“A drug interaction of this magnitude might contribute to the development of [Gleevec] resistance and treatment failures,” write the researchers.

“Clinicians should be aware that St. John’s Wort may reduce [Gleevec] exposure by 30%-40%, and take appropriate actions to educate patients receiving [Gleevec] treatment.”

St. John’s Wort appears to speed up metabolism of Gleevec, ushering it out of the body before it has the chance to fully exert its effects. As a result, the body could stop responding to Gleevec, since it’s not present at appropriate blood levels.

St. John’s Wort is unregulated in the U.S., so it’s impossible to know the exact dose of each bottle sold in America. For that reason, St. John’s Wort’s interaction with Gleevec may be even greater in some cases, as well as in certain people who may be more sensitive to such effects, say the researchers.

A Call for Full Disclosure

Patients taking herbal supplements need to tell their health care providers about it, say Smith and colleagues, who cite studies that say about a third to one-half of all cancer patients use some type of alternative medicine, such as vitamins and herbal supplements.

Too often, the public is unaware that such preparations can interact with and even undermine their prescription medications.

That’s not to say that depression and mood concerns, which are the main reasons why people take St. John’s Wort, aren’t important. The best approach may be discussing all supplements and remedies with a doctor, along with the problems that prompted interest in those preparations in the first place.


SOURCES: Smith, P. “The Influence of St. John’s Wort on the Pharmacokinetics and Protein Binding of Imatinib Mesylate.” News release, University of Buffalo. WebMD Medical News: “Gleevec New CML Gold Standard.” WebMD Medical News: “FDA Approves ‘Breakthrough’ Leukemia Drug.” WebMD Medical News: “St. John’s Wort Reduces Chemotherapy Effects.”

 

http://my.webmd.com/content/article/95/103536.htm

SRC Kinase Inhibition with BMS-354825 in Pancreatic Cancer Models

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Src kinase is an enzyme that may contribute to the ability of pancreatic cancer cells to metastasize or spread. BMS-354825 is an experimental compound that inhibits Src kinase.

Dr. Hong’s preliminary research shows that BMS-354825 inhibits Src kinase in pancreatic cancer cells in the laboratory. The inhibition of Src kinase then inhibits vascular endothelial growth factor (VEGF) in these cells. VEGF contributes to the ability of cancer cells to form new blood vessels and create a blood supply for the tumor. Dr. Hong hypothesizes that BMS-354825 may be an effective treatment for pancreatic cancer.

He will test his hypothesis first by determining if BMS-354825 kills isolated pancreatic cancer cells in the lab. Then, he will combine BMS-354825 with gemcitibine to determine if the two compounds together kill the isolated pancreatic cancer cells. Lastly, he will evaluate the antitumor activity of BMS-354825 alone and with gemcitibine in mouse models of pancreatic cancer.

http://www.pancan.org/Research/davidhong.htm