Posted by rob on October 15, 2005 under Uncategorized | 
Jørgensen HG, Allan EK, Mountford JC, Richmond L, Harrison S, Elliott MA, Holyoake TL
Exp Hematol. 2005 Oct ; 33(10): 1140-6
OBJECTIVE: In chronic myeloid leukemia (CML), imatinib mesylate (IM; Gleevec, Glivec) induces a G0/G1 cell-cycle block in total CD34(+) cells without causing significant apoptosis. Bryostatin-1 (bryo), a protein kinase C (PKC) modulator, was investigated for its ability to increase IM-mediated apoptosis either through induction of cycling of G0/G1 Ph(+) cells or antagonism of the IM-induced cell-cycle block. METHODS: The Ph(+) K562 cell line and primary CD34(+) CML cells were studied for cell-cycle progression (PI staining), proliferation ((3)H thymidine uptake), and survival (dye exclusion). RESULTS: Following 48 hours exposure to IM, on average more than 80% of surviving K562 cells were in G0/G1 as compared to approximately 50% for untreated control cultures (p
Enhanced CML stem cell elimination in vitro by bryostatin priming with imatinib mesylate.
Posted by rob on under Uncategorized |
Gleich GJ, Leiferman KM
Curr Opin Immunol. 2005 Oct 5;
In 1968, the term hypereosinophilic syndromes (HES) was coined to refer to a spectrum of eosinophil-associated diseases presumed to be caused by an underlying immunological pathology. In the 1990s, the identification of an HES subset with T lymphocyte clonality and production of cytokines, particularly IL-5, validated this concept. Then, in 2002, imatinib mesylate, which was introduced for the treatment of chronic myelogenous leukemia, effectively controlled another subgroup of HES patients. Imatinib’s target is a novel constitutively-active kinase. Most imatinib-responsive HES patients show an increased number of bone marrow mast cells and elevated serum tryptase; mast cells, lymphocytes and neutrophils express the novel kinase. This new information critically modifies our view of HES and indicates that several cell lines are altered and likely to contribute to HES pathophysiology.
The hypereosinophilic syndromes: still more heterogeneity.
Posted by rob on under Uncategorized |
Dick Shaffer is forever grateful for the doctors and nurses who successfully treated his cancer in a clinical trial two years ago. He never would have met them, however, without the person who suggested he consider an experimental study.
For that reason, Shaffer has vowed to do everything he can to encourage other cancer patients to consider enrolling in clinical trials. He started by joining the Bristol-Myers Squibb Tour of Hope™ team of 24 cyclists who this month completed a 3,300-mile, cross-country bicycle ride aimed at boosting low clinical trial participation nationwide. The tour, led by cancer survivor and seven-time Tour de France winner Lance Armstrong, began in San Diego on Sept. 29 and ended in Washington D.C., on Oct. 8, Shaffer’s 59th birthday.
Riders in four teams of six made the journey by taking turns cycling about 100 miles a day (four or five hours). At the end of a team’s shift, the cyclists were transported to food and lodging and then taken to the next starting point to catch up with their teammates.
The trip was challenging and extremely rewarding, says Shaffer, a retired utility company finance director from upstate New York who has competed in triathlons since 1984. Just a few years before the tour, he was diagnosed with stage 3 esophageal cancer and given the prognosis of a 20% chance of survival – at best.
“This is a celebration for me,” Shaffer says. “It’s a chance to say, ‘in your face, cancer,’ and a chance to tell people there is hope. People need to know that cancer is not always a death sentence, and we need clinical trials because they are the only way to beat cancer in the long run.”
Clinical trial message sent best: patient to patient
Shaffer knew nothing about clinical trials in 2003 when his doctor found a 5-centimeter tumor at the intersection of his esophagus and stomach.
The mass was discovered during a routine physical before Shaffer was to compete in his second Ironman triathlon. He signed up for the competition at the suggestion of his nephew, Mike Siegel, 45, the same person who encouraged him to start training for triathlons 20 years before.
During the physical, Shaffer happened to mention to the doctor that he was having trouble swallowing vitamins. The doctor then ordered an endoscopy and discovered the tumor. Shaffer visited several doctors after that, receiving one poor prognosis after another.
Then Siegel suggested he try a clinical trial. It had worked for him.
Siegel was diagnosed with chronic myelogenous leukemia (CML) in April 1995 and given a 50% chance of survival with standard cancer treatments. Looking for better odds, the then father of three (with twins on the way) sought experimental treatments, therapies only available in clinical trials. Two studies have kept him alive since then, he says. The second trial involved the drug now called Gleevec®, which he continues to take today.
“I watched the twins being born and growing up, and they’re now 10 – and an earful,” says Siegel, who was treated at M. D. Anderson. “So I tell patients, ‘Clinical trials saved my life – twice. Don’t be afraid. Ask about a clinical trial.’”
Taking the leap of faith in a clinical trial pays off
At first, Shaffer resisted that suggestion. He didn’t know anything about clinical trials and was afraid. But then he thought about the people who needed him most, his wife and two young sons, then 8 and 13. He searched for a trial that might lead to a better possibility of survival, and found one at M. D. Anderson.
Entering the study, however, meant moving to Houston for six months and leaving his family behind so his sons could remain in school. “They wanted me home. I’ll never forget the day I said goodbye at the airport,” Shaffer says. “It was hard.”
Shaffer’s wife, Julie, took care of the kids in New York, and Shaffer left for Houston. Fortunately, his sister and brother-in-law moved with him to become his caregivers.
His treatment was aggressive: 12 weeks of chemotherapy (involving a combination of three drugs), 12 weeks of chemotherapy and radiation and, finally, surgery to remove half of his stomach and half of his esophagus.
The medication made him very sick, but he was upbeat during his twice-daily phone calls with his sons. Shaffer even managed to bike during the period he received chemotherapy and radiation. He kept such a positive attitude throughout his treatment that patients and doctors said he made them feel better. “I was so determined to beat this thing, I think,” he says.
Patient’s struggle and journey of hope comes full circle
And that he did. After treatment he reunited with his family, built up his strength and even competed with his wife in the Houston marathon. Next thing he knew he was taking another cue from his nephew, a 2004 cyclist in the Tour of Hope, by becoming a tour member himself.
Siegel joined Shaffer, Armstrong and the rest of the 2005 Tour of Hope team as they rode through the Texas Medical Center for an Oct. 3 stop at M. D. Anderson. Events there included a rally, press conference and a panel discussion about clinical trials.
Siegel was near the rally podium where, as one of the speakers, Shaffer was able to live out his dream of thanking every member of the medical team who helped eliminate his cancer.
His emotional thank-you touched the crowd made up of the public and hundreds of yellow-clad cancer center employees. Shaffer’s former nurses cheered the loudest, holding huge campaign-like signs bearing his photo. Armstrong joked that Shaffer might threaten Houston Mayor Bill White’s re-election bid.
Shaffer just hoped his experience might lead other cancer patients to new treatments that might free them of cancer.
CancerWise – October 2005 – Clinical Trial Patients Spread the Word: Hope
