Pic Of The Day
Posted by rob on February 27, 2005 under Uncategorized | 
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A Russian model presents hair design ‘Wedding’ at a show at the St.Petersburg international contest
CHS senior battling leukemia
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CHS senior battling leukemia
When Brittany Randle’s knees started aching during the first week of soccer practice earlier this month, she scheduled an appointment with her family physician.
“I couldn’t even get up in the mornings,” Randle said.
The popular Ceres High senior was diagnosed with leukemia on Thursday.
“If anybody can fight this thing and be successful, it’s Brittany Randle,” said Ceres High varsity girls soccer coach Randy Cerny. “She has strong faith.”
Added Randle: “A lot of people are taking it worse than I am. I just have to get it treated.”
Randle watched the Ceres High varsity girls basketball team compete against the Davis Spartans in Ceres Thursday night. She was greeted with hugs from students and administrators, including Ceres High principal Bob Palous.
“Everybody is rallying around her,” Cerny said.
Said Randle: “It’s just nice to know I have a lot of support.”
Randle has chronic myelogenous leukemia (CML). The diagnosis was made after a specialist in Modesto examined her blood and marrow cell.
About 4,600 new cases of CML are diagnosed each year in the United States. CML results from an acquired (not inherited) injury to the DNA of a stem cell in the marrow. The result of this injury is the uncontrolled growth of white cells leading, if unchecked, to a massive increase in their concentration in the blood.
“The average person has 4,000 to 13,000 white cells,” Randle said. “I had 109,000.”
Randle started treatment the day she was diagnosed. She was prescribed an oral medication. Randle takes a pill four times a day.
“If the pills don’t work, I’m going to have to get a bone marrow transplant,” she said.
On Monday morning, Randle visited her teammates at practice at Walter White School.
“She’s going to continue to be a part of this team,” Cerny said. “In what capacity, I don’t know. If she could even step on the field for one minute, she would.”
Randle played in just about every game for the varsity Bulldogs the last three years. As a starter on defense, Randle earned second-team, all-Central California Conference honors as a sophomore and was an honorable-mention selection as a junior.
The Bulldogs will miss Randle’s leadership on the field.
“It’s hard,” Randle said. “This is the time I’m supposed to be training the hardest for college. That’s the worse part of it. I can’t play.”
Added Cerny: “We don’t have anybody at our school that can replace that girl. She has some great ability.
“She leads by example. She goes out and plays hard and it brings up the level of play for the girls that are around her.”
Cerny and Randle have a great relationship off the field.
She’s been babysitting for his family the last four years.
“Brittany Randle is a top-quality person,” Cerny said. “She’s honorable. She’s ethical. She’s intelligent. She’s athletic. She has a great sense of humor. She’s a very friendly person. I love that kid.”
The Leukemia & Lymphoma Society contributed to this report. – By DALE BUTLER /
Study finds mechanism for drug resistence
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Study finds mechanism for drug resistence
Source: (cancerfacts.com)
Friday, February 25, 2005
BOSTON – Feb. 25, 2005 – A new study shows that a second mutation in a gene associated with non-small-cell lung cancer (NSCLC) helps to explain how the tumors become resistant to new generation drugs like gefitinib (Iressa®).
Led by Dr. Balazs Halmos, a physician-scientist formerly at Beth Israel Deaconess Medical Center and now with the University Hospitals of Cleveland, and Dr. Daniel Tenen, a molecular biologist at Beth Israel, the researchers found that the non-small cell lung tumors appear to develop a second mutation that allows them to evade the action of the new generation drugs.
“The development of a second mutation suggests that the tumor cells remain dependent on an active EGFR pathway for their proliferation,” Tenen said in a prepared statement. “This mirrors the situation that developed over the past few years among patients with chronic myeloid leukemia and gastrointestinal stromal tumors who were being treated with imatinib (Gleevec®).”
The new drugs are designed to target a specific gene mutation that produces an abnormal epidermal growth factor protein (EGFR), which allows the tumor to grow unchecked. Gleevec is a similarly designed drug that has been very effective in the treatment of a certain type of leukemia. In some people, however, Gleevec seems to gradually lose effectiveness.
In those cases, says Tenen, who is also a professor of medicine at Harvard Medical School, the identification of mechanisms of resistance helped lead to the development of second-generation inhibitor drugs. The new study appears in the Feb. 24, 2005 issue of The New England Journal of Medicine.
Gefitinib is one of a new generation of cancer drugs that work by disrupting a specific molecular target within the cell. In this case the abnormal protein responsible for stimulating tumor growth. Gefitinib acts on the receptor for the epidermal growth factor protein (EGFR) to halt the proliferation of cancer cells. In 2003, it was approved by the U.S. FDA as a treatment for non-small cell lung cancer.
Clinical applications of the new drug initially yielded very encouraging results, with approximately 10 percent of patients experiencing complete remissions. Unfortunately, the remissions were not long-lived and the cancer returned.
Hypothesizing that the relapses may have been due to another mutation in the EGFR gene that was causing cancer cells to become resistant to the drug, the researchers obtained a second tissue sample of the tumor from patients treated with gefitinib and resequenced, or remapped, the genetic sequence of the EGFR gene.
Their studies confirmed the existence of a second mutation, and insertion of this mutation into cells in test tubes made them resistant to gefitinib. Further analysis showed that the newly identified mutation was altering gefitinib’s binding pocket and thereby changing the “keyhole” so that the “key” in gefitinib no longer fit.
According to study coauthor Dr. Bruce Johnson, director of the Dana-Farber/Harvard Cancer Center Lung Program, clinical investigators are already moving to develop a new drug designed to overcome this second mutation.
“Our preliminary results have yielded encouraging findings, pointing towards drugs that might bypass this method of resistance,” says Johnson. “We’re now in the process of planning clinical studies to test novel EGFR inhibitor compounds in lung-cancer patients whose tumors have become resistant to gefitinib.”
Improved outcome in HLA-identical sibling hematopoietic stem cell transplantation for acute myelogenous leukemia (AML) predicted by KIR and HLA genotypes.
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Improved outcome in HLA-identical sibling hematopoietic stem cell transplantation for acute myelogenous leukemia (AML) predicted by KIR and HLA genotypes.
Hsu KC, Keever-Taylor CA, Wilton A, Pinto C, Heller G, Arkun K, O’reilly RJ, Horowitz MM, Dupont B
Blood. 2005 Feb 24;
Inhibitory killer Ig-like receptors (KIR) recognize HLA-C and -B epitopes on target cells, thereby regulating natural killer (NK) cell activity. In 178 patients receiving T-cell depleted HLA-identical sibling transplants for CML, ALL, AML, and MDS, analysis of donor KIR genotype with HLA genotype demonstrated that 62.9% of the patients lacked an HLA ligand for donor inhibitory KIR. Lack of HLA ligand for donor inhibitory KIR (“missing KIR ligand”) had no effect on disease-free survival (DFS), overall survival (OS), or relapse in patients receiving transplants for CML and ALL. There was, however, a significant missing KIR ligand effect in AML and MDS on DFS (p=0.014, HR 0.53, 95% CI 0.28-0.88) and OS (p=0.03, HR 0.53, 95% CI 0.3-0.93). Incidence of relapse was also lower in AML and MDS patients lacking HLA ligand for donor inhibitory KIR (p=0.04, HR 0.41, 95% CI 0.18-0.97). AML and MDS patients lacking two HLA ligands for donor inhibitory KIR had the highest DFS (p=0.002) and OS (p=0.003). There was no significant contribution of donor activating KIR to transplant outcome in these patients. These data indicate that absence of class I ligand in the recipient for donor inhibitory KIR can be a prognostic factor for transplant outcome in HLA-identical sibling transplants, and that lack of either HLA-C or -B ligands for donor inhibitory KIR can contribute to improved outcome in AML and MDS.
[Experimental study of K562 cell apoptosis induced by siRNA.]
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[Experimental study of K562 cell apoptosis induced by siRNA.]
Chen BB, Fan HH, Lin GW, Yuan ZH, Lu HZ, Gao L, Liu Y
Zhonghua Xue Ye Xue Za Zhi. 2004 Dec ; 25(12): 717-9
OBJECTIVES: To construct a siRNA expression vector pBCR6 that produces siRNA against bcr/abl mRNA and detect apoptosis rate of K562 cells after pBCR6 transfection. METHODS: Template sequence for siRNA was designed, synthesized and inserted into an expression vector pSilencer1.0-U6. Restriction analysis and sequencing were performed to verify the pBCR6 vector. Then pBCR6 was transfected into K562 cells by X-tremeGene Q2. pSilencer1.0-U6 was used as the control. At different time point after transfection, apoptosis rate was determined by Tunel and Annexin V+ PI with FCM. RESULT: pBCR6 was verified by restriction analysis and sequencing. The apoptosis rate of K562 cells markedly increased at 48 and 72 hour after transfected with pBCR6, and increased in a time-dependent manner [the apoptosis rate of transfected K562 cells was (47.80 +/- 1.63)% at 72 hrs, wheras the control group was (6.67 +/- 0.37)%, P
[Experimental study of K562 cell apoptosis induced by siRNA.]
Pharmacogenomics and the Drug Discovery Pipeline : When Should it Be Implemented?
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Pharmacogenomics and the Drug Discovery Pipeline : When Should it Be Implemented?
Penny MA, McHale D
Am J Pharmacogenomics. 2005; 5(1): 53-62
One of the key factors in developing improved medicines lies in understanding the molecular basis of the complex diseases we treat. Investigation of genetic associations with disease utilizing advances in linkage disequilibrium-based whole genome association strategies will provide novel targets for therapy and define relevant pathways contributing to disease pathogenesis. Genetic studies in conjunction with gene expression, proteomic, and metabonomic analyses provide a powerful tool to identify molecular subtypes of disease. Using these molecular data, pharmacogenomics has the potential to impact on the drug discovery and development process at many stages of the pipeline, contributing to both target identification and increased confidence in the therapeutic rationale. This is exemplified by the identified association of 5-lipoxygenase-activating protein (ALOX5AP/FLAP) with increased risk of myocardial infarction, and of the chemokine receptor 5 (CCR5) with HIV infection and therapy. Pharmacogenomics has already been used in oncology to demonstrate that molecular data facilitates assessment of disease heterogeneity, and thus identification of molecular markers of response to drugs such as imatinib mesylate (Gleevec((R))) and trastuzumab (Herceptin((R))).Knowledge of genetic variation in a target allows early assessment of the clinical significance of polymorphism through the appropriate design of preclinical studies and use of relevant animal models. A focussed pharmacogenomic strategy at the preclinical phase of drug development will produce data to inform the pharmacogenomic plan for exploratory and full development of compounds. Opportunities post-approval show the value of large well-characterized data sets for a systematic assessment of the contribution of genetic determinants to adverse drug reactions and efficacy. The availability of genomic samples in large phase IV trials also provides a valuable resource for further understanding the molecular basis of disease heterogeneity, providing data that feeds back into the drug discovery process in target identification and validation for the next generation of improved medicines.
Pharmacogenomics and the Drug Discovery Pipeline : When Should it Be Implemented?