Shadow Dancing
Posted by rob on July 27, 2006 under Uncategorized | 
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From columbo’s dad
CML Newswire Moves To WordPress
Posted by rob on July 26, 2006 under Uncategorized | 7 Comments to Read
Because of frequent problems with the Blogger/Blogspot system future articles of CML Newswire will be posted at http://cmlnewswire.wordpress.com Old articles will still be archived at http://cmlsupport.blogspot.com
Cardiotoxicity of the cancer therapeutic agent imatinib mesylate.
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Cardiotoxicity of the cancer therapeutic agent imatinib mesylate.
Kerkela R, Grazette L, Yacobi R, Iliescu C, Patten R, Beahm C, Walters B, Shevtsov S, Pesant S, Clubb FJ, Rosenzweig A, Salomon RN, Van Etten RA, Alroy J, Durand JB, Force T.
[1] Center for Translational Medicine, Jefferson Medical College, 1025 Walnut Street, Philadelphia, Pennsylvania 19107, USA. [2] The Molecular Cardiology Research Institute, Tufts-New England Medical Center and Tufts University School of Medicine, 750 Washington Street, Boston, Massachusetts 02111, USA.
Imatinib mesylate (Gleevec) is a small-molecule inhibitor of the fusion protein Bcr-Abl, the causal agent in chronic myelogenous leukemia. Here we report ten individuals who developed severe congestive heart failure while on imatinib and we show that imatinib-treated mice develop left ventricular contractile dysfunction. Transmission electron micrographs from humans and mice treated with imatinib show mitochondrial abnormalities and accumulation of membrane whorls in both vacuoles and the sarco- (endo-) plasmic reticulum, findings suggestive of a toxic myopathy. With imatinib treatment, cardiomyocytes in culture show activation of the endoplasmic reticulum (ER) stress response, collapse of the mitochondrial membrane potential, release of cytochrome c into the cytosol, reduction in cellular ATP content and cell death. Retroviral gene transfer of an imatinib-resistant mutant of c-Abl, alleviation of ER stress or inhibition of Jun amino-terminal kinases, which are activated as a consequence of ER stress, largely rescues cardiomyocytes from imatinib-induced death. Thus, cardiotoxicity is an unanticipated side effect of inhibition of c-Abl by imatinib.
PMID: 16862153 [PubMed - as supplied by publisher]
More Articles On Gleevec Heart Damage
Posted by rob on July 24, 2006 under Uncategorized | Be the First to Comment
Leukemia drug Gleevec may damage heart: study
Xinhua, China - 1 hour ago
BEIJING, July 24(Xinhuanet) — Leukemia treatment drug Gleevec produced by the Swiss Novartis Pharmaceuticals may lead to severe heart damage, researchers …
| Leukemia drug Gleevec may damage heart: study Xinhua, China - 1 hour ago BEIJING, July 24(Xinhuanet) — Leukemia treatment drug Gleevec produced by the Swiss Novartis Pharmaceuticals may lead to severe heart damage, researchers … |
| Study: Successful cancer drug may damage heart Jerusalem Post, Israel - 3 hours ago A successful cancer-fighting drug may also damage the heart, although a researcher says leukemia patients who need Gleevec should not abandon it. … |
| Heart failure is side effect of cancer drug Scotsman, United Kingdom - 3 hours ago A REVOLUTIONARY cancer treatment available in Scotland and which was hailed a “wonder drug” can damage the heart, scientists have warned. … |
| Leukaemia drug link to heart failure Times Online, UK - 3 hours ago By Mark Henderson. THE safety of a drug hailed as the harbinger of a new era of cancer therapy has been called into question by research … |
| Irish-made cancer drug ‘can lead to heart failure’ Irish Examiner, Ireland - 4 hours ago By John von Radowitz. A REVOLUTIONARY cancer treatment hailed as a “wonder drug” can damage the heart, scientists warn. The Irish … |
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Cancer drug ‘toxic to the heart’ BBC News, UK - 4 hours ago A widely hailed cancer drug can damage cardiac tissue and may lead to heart failure, research shows. Glivec has boosted survival … |
| Cancer drug Gleevec may damage heart: study Boston Globe, United States - 7 hours ago By Maggie Fox, Health and Science Correspondent | July 23, 2006. WASHINGTON (Reuters) – Gleevec, the pill that transformed cancer … |
| Novartis Cancer Drug Gleevec May Harm Heart, Researchers Say Bloomberg - 8 hours ago July 23 (Bloomberg) — Novartis AG’s Gleevec cancer drug may harm patients’ hearts, researchers said after studying the product in mice and a small group of … |
| Cancer drug Gleevec may damage heart MSN Money - 11 hours ago WASHINGTON (Reuters) – Gleevec, the pill that transformed cancer treatments by offering an easy way to target a difficult type of leukemia, may cause serious … |
| UPDATE 1-Cancer drug Gleevec may damage heart – study Reuters - 11 hours ago By Maggie Fox, Health and Science Correspondent. WASHINGTON, July 23 (Reuters) – Gleevec, the pill that transformed cancer treatments … |
| Heart Risks Found With Gleevec Wall Street Journal (subscription), NY - 11 hours ago By JEANNE WHALEN. A small but significant study of Novartis AG’s cancer drug Gleevec shows that it can be toxic to the heart and … |
| Study: Cancer drug may pose heart danger Seattle Post Intelligencer - 11 hours ago By RANDOLPH E. SCHMID. WASHINGTON — A successful cancer-fighting drug may also damage the heart, although a researcher says leukemia … |
| ‘Miracle’ cancer drug may hurt heart Philadelphia Inquirer, PA - 1 hour ago By John Sullivan. Doctors at Thomas Jefferson University have discovered why the wonder drug Gleevec, heralded for turning off cancer … |
| Leukemia Drug Glevic Shown to Promote Heart Failure Dog Flu Diet and Diseases, Canada - 3 hours ago By Laura Watson. It is being reported in the online Nature Medicine, that a popular cancer drug can be dangerous to heart tissue. … |
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Gleevec Linked To Heart Failure World Fitness, Canada - 7 hours ago By Mia Blake. The cancer treatment drug Gleevec, used to treat chronic myelogenous leukemia may also damage the heart, according … |
| Study says cancer-fighting drug may pose heart danger KTRE, TX - 8 hours ago WASHINGTON A successful cancer treatment may also damage the heart, but one researcher says it remains a “lifesaving” drug. A study … |
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Leukemia Cancer Drugs May Cause Heart Failure – Gleevec and Other … Best Syndication, CA - 8 hours ago New drugs used to treat leukemia, including Gleevec, may cause serious heart damage, according to US researchers. The researchers … |
| ?Miracle? cancer drug may hurt heart Therapeutics Daily (subscription) (press release), PA - 9 hours ago Doctors at Thomas Jefferson University have discovered why the wonder drug Gleevec, heralded for turning off cancer cells, may also cause congestive heart … |
| “Miracle” Cancer Drug Gleevec Can be Toxic to the Heart Newswise (press release) - 10 hours ago Newswise — Gleevec, the wildly successful poster-child of a new generation of cancer drugs aimed at specific targets in the cancer cell, can be dangerous to … |
| Cancer drug may damage heart, says study New Zealand Herald, New Zealand - 58 minutes ago WASHINGTON – Gleevec, the pill that transformed cancer treatments by offering an easy way to target a difficult type of leukaemia, may cause serious heart … |
| Cancer drug could damage human heart – study Independent Online, South Africa - 3 hours ago By Maggie Fox. Washington – Gleevec, the pill that transformed cancer treatments by offering an easy way to target a difficult type … |
| Study: Cancer Drug May Pose Heart Danger Houston Chronicle, United States - 3 hours ago By RANDOLPH E. SCHMID AP Science Writer. WASHINGTON — A successful cancer-fighting drug may also damage the heart, although a researcher … |
| Study: Cancer drug may pose heart danger BusinessWeek - 3 hours ago JUL. 23 8:20 PM ET A successful cancer-fighting drug may also damage the heart, although a researcher says leukemia patients who … |
| Warning Is Issued on Drug for Leukemia New York Times, United States - 3 hours ago By REUTERS. Gleevec, the pill that transformed cancer treatments by offering an easy way to aim at a deadly type of leukemia, may … |
| Study: Cancer Drug May Pose Heart Danger Forbes - 4 hours ago By RANDOLPH E. SCHMID , 07.23.2006, 08:08 PM. A successful cancer-fighting drug may also damage the heart, although a researcher … |
| Study: Cancer drug may pose heart danger San Jose Mercury News, USA - 4 hours ago WASHINGTON – A successful cancer-fighting drug may also damage the heart, although a researcher says leukemia patients who need Gleevec should not abandon it. … |
| Study: Cancer Drug May Pose Heart Danger Salon - 7 hours ago By RANDOLPH E. SCHMID AP Science Writer. July 23,2006 | WASHINGTON — A successful cancer-fighting drug may also damage the heart … |
| Cancer drug Gleevec may damage heart Reuters - 11 hours ago By Maggie Fox, Health and Science Correspondent. WASHINGTON (Reuters) – Gleevec, the pill that transformed cancer treatments by offering … |
| Cancer drug Gleevec may damage heart – study Reuters - 11 hours ago By Maggie Fox. WASHINGTON, July 23 (Reuters) – Gleevec, the pill that transformed cancer treatments by offering an easy way to target … |
| Study: Cancer Drug May Pose Heart Danger Wyoming News, WY - 2 hours ago By RANDOLPH E. SCHMID Sunday, July 23, 2006. WASHINGTON – A successful cancer-fighting drug may also damage the heart, although a … |
Gleevec May Cause Serious Heart Damage
Posted by rob on July 23, 2006 under Uncategorized | 3 Comments to Read
By Maggie Fox, Health and Science Correspondent 26 minutes ago
Gleevec, the pill that transformed cancer treatments by offering an easy way to target a difficult type of leukemia, may cause serious heart damage, researchers cautioned on Sunday.
They found evidence that treatment caused heart failure in 10 patients who took Gleevec, made by Swiss drugmaker Novartis.
Patients should not stop taking the drug, known generically as imatinib, but should be watched closely for heart damage, the team at Jefferson Medical College in Philadelphia, Tufts University School of Medicine in Boston, University of Texas and elsewhere said.
Other drugs in the same class, tyrosine kinase inhibitors, may also damage the heart, the researchers report in the August issue of the journal Nature Medicine.
“Gleevec is a wonderful drug and patients with these diseases need to be on it,” Thomas Force, who led the study, said in a statement.
“We’re trying to call attention to the fact that Gleevec and other similar drugs coming along could have significant side effects on the heart and clinicians need to be aware of this. It’s a potential problem because the number of targeted agents is growing rapidly.”
When Gleevec hit the market in 2001, it made headlines because it stopped a difficult type of cancer, chronic myelogenous leukemia or CML, in most patients. Studies show it keeps anywhere between 80 and 90 percent of CML patients cancer-free for at least five years.
Usually half of the 4,600 new CML patients diagnosed each year die.
Gleevec, sold in Europe as Glivec, is also approved for gastrointestinal stromal tumors or GIST, a rare type of stomach cancer.
It stops the activity of a protein called Bcr-Abl, which causes the out-of-control behavior of white blood cells in CML.
WATCHING PATIENTS
Force’s team studied the 10 human patients, who developed heart failure while taking Gleevec at M.D. Anderson Cancer Center in Houston. They then tested the drug in lab dishes and in mice. It appears to be toxic to cardiac cells, they said.
Mice treated with Gleevec developed left ventricular dysfunction, one of the key symptoms of heart failure in which the heart fails to pump out blood completely.
Patients taking Gleevec should be followed closely for symptoms of heart trouble, Force’s team advised.
“While the cancer is treated effectively, there will be some percentage of patients who could experience significant left ventricular dysfunction and even heart failure from this,” Force said in a statement.
Heart failure is a serious and chronic condition that itself kills up to half of patients withing five years.
Novartis said the cases of heart failure in Gleevec patients were extremely rare and said those few patients were successfully treated with two drugs that can help heart failure — ACE inhibitors and carvedilol.
“Further study is necessary to better understand the relationship between these preclinical studies and their potential impact on the clinical management of patients taking Glivec,” the company said in a statement.
Drug companies are working on several “second-generation” Gleevec-type drugs, and they could also cause the problem, Force said.
“The drugs are all tyrosine kinase inhibitors, but each tyrosine kinase is different,” Force said. “It’s difficult to predict what tyrosine kinases will have protective roles in the heart and inhibition of them will be toxic.”
(With additional reporting by Ben Hirschler in London)
Copyright © 2006 Reuters Limited.
Quantification of change in phosphorylation of BCR-ABL kinase and its substrates in response to Imatinib treatment in human chronic myelogenous leukemia cells.
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Reversible Peripartum Cardiomyopathy in a Patient with Prior Exposure to Interferon.
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Reversible Peripartum Cardiomyopathy in a Patient with Prior Exposure to Interferon.
Gene expression signatures associated with the resistance to imatinib.
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Gene expression signatures associated with the resistance to imatinib.
Glucosamine sulfate-induced apoptosis in chronic myelogenous leukemia K562 cells is associated with translocation of cathepsin D and downregulation of Bcl-xL.
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Myeloperoxidase-Catalyzed Metabolism of Etoposide to Its Quinone and Glutathione Adduct Forms in HL60 Cells.
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Successful outcome of pregnancy in a patient with chronic myelogenous leukemia exposed to imatinib during the first trimester.
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Intermittent dosage of imatinib mesylate in CML patients with a history of significant hematologic toxicity after standard dosing.
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Arkansas Lt. Gov. Win Rockefeller dies at 57 After 2 Failed BMT’s
Posted by rob on July 16, 2006 under Uncategorized | Be the First to Comment
By Steve Barnes
LITTLE ROCK, Arkansas (Reuters) – Arkansas Lt. Gov. Win Rockefeller, 57, a great-grandson of Standard Oil founder John D. Rockefeller, died on Sunday of complications relating to a blood disorder, a spokesman said in a statement.
Rockefeller, a wealthy Republican, was nearing the end of his second four-year term as lieutenant governor. He was diagnosed with myeloproliferative disorder last year, prompting him to end his campaign for governor.
Rockefeller was continuing a U.S. political dynasty that included his father Winthrop Rockefeller, who was governor of Arkansas from 1967 to 1971 and his uncle Nelson Rockefeller, who was New York governor from 1959 to 1973 before serving as U.S. vice president from 1974 to 1977.
He was a cousin of U.S. Sen. Jay Rockefeller, a Democrat from West Virginia.
Rockefeller sought treatment for his malady, which can lead to leukemia, at a Seattle cancer center earlier this year. But two bone marrow transplants failed to arrest the condition, and he returned to Arkansas by private plane on July 8.
Like his father and uncle, Rockefeller came from the moderate wing of the Republican Party, making his prospects for further office uncertain in the conservative-dominated party.
During his political career, Rockefeller said Forbes magazine overstated his fortune, which the magazine estimated to be $1.2 billion, making Rockefeller the 283rd richest American in Forbes’ latest rankings.
Rockefeller gave his annual $35,000 salary as lieutenant governor to charity.
Rockefeller operated Winrock Farms Inc., a cattle farm founded by his father atop Petit Jean Mountain, about 45 miles
west of Little Rock, and was an active supporter of Boy Scouts of America.
Rockefeller and his wife, Lisenne, founded a school in Arkansas for children with learning difficulties. Two of Rockefeller’s children have Down syndrome.
In addition to his wife, Rockefeller is survived by eight children and one grandchild.
ASCO Highlights
Posted by rob on July 1, 2006 under Uncategorized | Be the First to Comment
Managing Side Effects section covers 40+ of the most common treatment side effects, including five new topics: Bleeding and Clotting Problems, Edema, Headaches, Hand-Foot Syndrome, and Skin Reactions to Targeted Therapies.
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