Posted by rob on March 16, 2006 under Uncategorized | 
(RTTNews) – Wednesday, Praecis Pharmaceuticals Inc. (PRCS | charts | news | Powerrating), a biopharmaceutical company, presented an update on the development of its DirectSelect technology, a facilitator of drug discovery process, at the Drug Discovery Technology Europe 2006 meeting in London.
The DirectSelect technology is based on the creation of multiple, numerically, encoded libraries of drug-like structures that can be screened quickly to identify individual or families of structures, with affinity for a macromolecular target.
Dr. Morgan, VP, Chemistry, during the presentation, discussed the generation of a set of libraries having more than five billion compounds ready to identify small molecule drug candidates, as well as the application of these libraries in the identification of hit families to four well-known targets in proof-of-concept studies.
In the presentation, Dr. Morgan described proof-of-concept screening of the DirectSelect libraries against three kinase and one protease target, including the cancer targets Aurora A kinase and Gleevec-resistant mutant Abl T315I kinase, the inflammation target p38 map kinase, and the Alzheimer’s target beta secretase. In each case, new hit families were identified and hits were validated through re-synthesis, without tags used during the library screening, and testing in biochemical and cell-based assays, proving DirectSelect’s ability to rapidly identify and validate new hit families to pharmaceutical targets in a period of nearly a month. The technology was developed based on the line that the odds of identifying hits with higher affinity and enhanced selectivity for a macromolecular target can be improved by increasing the numeric size and “chemical space” interrogated by the target. In addition, access to multiple, structurally diverse families should improve the likelihood of identifying a lead molecule with a favorable safety profile in vivo. Praecis focused on combining validated chemistry methods with unique screening and deconvolution steps, the company stated.
The company revealed that it initiated activities to screen for new compounds against therapeutic targets of interest. The Company intends to use the DirectSelect technology to engage in advance research collaborations and pharmaceutical partnerships in drug discovery and development. The Company said it plans to use this technology to expand its own proprietary development pipeline.
PRCS is currently trading at $5.81, up $0.14, on 28,847 shares.
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Posted by rob on March 8, 2006 under Uncategorized |
Public release date: 7-Mar-2006
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Contact: Eric Vohr
evohr1@jhmi.edu
410-955-8665
Johns Hopkins Medical Institutions
New strategy developed to study disease: Reveals insights into cancer and treatment leads
For the first time, Johns Hopkins researchers were able to easily jumpstart the activity of a well-known cancer protein in live cells with a small molecule, a strategy that pinpointed key players in the cancer process and can be used to determine new therapeutic targets. What’s more, the scientists’ study, published in the March 3 issue of Science, identifies a simple method to further understand the complex mechanisms that underlie cancer as well as other diseases and may provide an easy model to screen for new cancer drugs.
“Our study reveals a new way to study proteins in live cells, in this case, a tyrosine kinase implicated in causing cancer,” says the study’s lead author, Philip A. Cole, M.D., Ph.D., director of the Department of Pharmacology and Molecular Sciences at The Johns Hopkins University School of Medicine. “This approach helped identify potentially important therapeutic targets and in the future may provide a method to easily screen cancer treatments.”
In the study, Cole and his colleagues examined the tyrosine kinase Src (pronounced SARK), a clinically important cancer protein that scientists have heavily studied but do not completely understand. The Johns Hopkins researchers developed a special mutated version of the Src protein and incorporated it into live animal cells. The mutated version was inactive but contained an “ignition switch” that would turn it back on. They determined that the small molecule, imidazole, could act as the key. Imidazole fit into a pocket in the mutated structure of the Src protein, which mended the structure and reinstated Src’s activity. Removal of imidazole quickly shut the protein off again.
“This strategy provided a controlled environment to study Src,” says Cole. “This helped us uncover some new and unexpected insights into how the cancer protein creates its havoc, as well as new treatment leads.” For one, the model provided evidence that Src interacts with CrkL, a signaling protein not previously known to be targeted by Src’s actions. The study also found direct evidence that Src activates MAP kinase pathways, which help transfer information from growth factors, molecules that aid in the development of cancer cells. Previously the role of Src in these pathways was controversial.
“Understanding the functions of different proteins in normal states and disease states is crucial for treatment development because it can help identify new therapeutic targets,” says Cole. Insights into tyrosine kinases could be particularly important for determining new cancer treatments, since scientists think that many different types are involved. “For example, Gleevec, which is used to treat gastrointestinal stromal tumors and chronic myeloid leukemia, is the most successful magic bullet against cancer in many years and works by blocking tyrosine kinase activity,” Cole says.
As a next step, Cole and his colleagues plan to further examine the role of Src in cancer using their new model. They also plan to adapt the approach to develop a drug screen.
In the future, it also may be possible to use their chemical technique to mend mutated proteins found in people with certain genetic diseases, according to Cole. For example, the immune system disorder agammaglobulinemia involves mutated tyrosine kinases. Possibly researchers could identify a small molecule that rescues the activity of the mutated tyrosine kinases in the same way that imidazole corrected the structure of the mutated Src and jumpstarted its activity.
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Other contributors to this study include Akhilesh Pandey, M.D., Ph.D., an assistant professor in the Institute of Genetic Medicine; Jin Zhang, Ph.D., an assistant professor in the Department of Pharmacology and Molecular Science, and Henrik Molina, M.S., a lab manager in the Institute of Genetic Medicine
New strategy developed to study disease: Reveals insights into cancer and treatment leads
Posted by rob on under Uncategorized |
By Herbert Lash Mon Mar 6, 11:54 AM ET
NEW YORK (Reuters) – An American couple that retires at age 65 will, on average, need $200,000 in retirement to cover out-of-pocket medical costs, Fidelity Investments, the No. 1 mutual fund firm, said on Monday.
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That amount, considered the biggest single expense for most people in retirement, increased 5.3 percent from $190,000 last year, said Brad Kimler, a senior vice president of Fidelity Employer Services Co., a company division.
The increase mostly resulted from the rising cost of health care and has gone up an average 5.8 percent a year since Fidelity began releasing the estimate in 2002, the company said.
The number is important as Fidelity has found that most people don’t take into account health care when planning for their retirement, and because the number of companies offering health benefits to retirees is declining, Kimler said.
Health-care costs have the potential to significantly erode retirement savings, he said.
“This is the one most frequently overlooked by people when they’re doing their retirement planning,” he said.
The amount people will need in retirement to cover out-of-pocket health costs will vary because of the medical needs they may encounter, he said. Being healthy before retirement will likely lesson medical costs later, he said.
Fidelity at first didn’t provide an estimate for individuals but later said the cost for males would be $90,000 over 17 years, and $110,000 for females over 20 years. The estimate for health-care costs assumes that retirees do not have employer-sponsored retiree health care, but includes three typical costs: expenses associated with Medicare part B and D premiums, Medicare cost-sharing provisions — co-payments, coinsurance, deductibles and excluded benefits — and prescription drug out-of-pocket costs.
It does not include other health expenses, such as over-the-counter medications, most dental services and long-term care.
Retired couple seen with $200,000 health need – Yahoo! News
Posted by rob on March 6, 2006 under Uncategorized |
Contact: Tory Harris
tah@temple.edu
215-707-1731
Temple University
Internet research builds cancer patients’ confidence
Newly diagnosed cancer patients who use the Internet to gather information about their disease have a more positive outlook and are more active participants in their treatment, according to a new Temple University study published in the March 2006 issue of the Journal of Health Communication.
“This is the first study to look at the relationship between Internet use and patient behaviors,” said principal investigator and public health professor Sarah Bass, Ph.D. “We wanted to see if access to readily available information about their condition helped patients to cope with issues such as hair loss and other treatment side effects.”
For this study, the researchers recruited patients who called a National Cancer Institute-funded 1-800 number, where trained specialists answered questions about the disease and directed callers to cancer-related resources in their area. Once selected, the 442 participants were broken into “direct user, indirect user and non user” categories based on their Internet usage patterns.
According to Bass, direct and indirect users tended to be females between the ages of 50 and 60 who had graduated from college and made more than $60,000 a year.
During the survey, Bass and her colleagues began to see strong parallels between Internet use and the patients’ feelings about their treatment. Those who used the Internet and those who received Internet information from family members or friends were more likely to view their relationship with their doctors as a partnership, and were more comfortable asking questions and challenging treatment alternatives.
“They saw the Internet as a powerful tool that enhanced their decision-making ability,” Bass said.
Moreover, Bass and her team were pleasantly surprised by the number of early non-users who after eight weeks turned to the Internet for information. When asked about the change, approximately 75 percent said that either family/friend encouragement or the cancer diagnosis itself prompted them to increase their Internet use.
“They didn’t want to feel powerless or have to rely on the doctor to make all of the decisions,” Bass said.
Bass warns that as more and more funding is cut for medical phone hotlines, now is the time for doctors and health workers to encourage patients to do their own research on the Web. “But as with most things, let the buyer beware. Stick to Web sites that are associated with large, well-recognized non-profit groups, or get recommendations from your physician.”
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The complete study can be viewed @ http://www.temple.edu/news_media/bass_study.html
Internet research builds cancer patients’ confidence
Posted by rob on under Uncategorized |
Yang H, Eaves C, de Lima M, Lee MS, Champlin RE, McMannis JD, Robinson SN, Niu T, Decker WK, Xing D, Ng J, Li S, Yao X, Eaves AC, Jones R, Andersson BS, Shpall EJ.
1Department of Blood and Marrow Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Imatinib-refractory chronic myelogenous leukemia (CML) patients can experience long-term disease-free survival with myeloablative therapy and allogeneic hematopoietic cell transplantation; however, associated complications carry a significant risk of mortality. Transplantation of autologous hematopoietic cells has a reduced risk of complications, but residual tumor cells in the autograft may contribute to relapse. Development of methods for purging tumor cells that do not compromise the engraftment potential of the normal hematopoietic cells in the autograft has been a long-standing goal. Since primitive CML cells differentiate more rapidly in vitro than their normal counterparts and are also preferentially killed by mafosfamide and imatinib, we examined the purging effectiveness on CD34(+) CML cells using a strategy that combines a brief exposure to imatinib (0.5-1.0 muM for 72 h) and then mafosfamide (30-90 mug/ml for 30 min) followed by 2 weeks in culture with cytokines (100 ng/ml each of stem cell factor, granulocyte colony-stimulating factor and thrombopoietin). Treatment with 1.0 muM imatinib, 60 mug/ml mafosfamide and 14 days of culture with cytokines eliminated BCR-ABL(+) cells from chronic phase CML patient aphereses, while preserving normal progenitors. This novel purging strategy may offer a new approach to improving the effectiveness of autologous transplantation in imatinib-refractory CML patients.Bone Marrow Transplantation advance online publication, 23 January 2006; doi:10.1038/sj.bmt.1705284.
PMID: 16435011 [PubMed - as supplied by publisher]
Entrez PubMed
Posted by rob on under Uncategorized |
P R Pilot1, K Sablinska2, S Owen1 and A Hatfield1
Reply to Roy et al. Leukemia advance online publication, 14 July 2005. Unexpected occurrence of second malignancies in patients treated with interferon followed by imatinib mesylate for chronic myelogenous leukemia. In their correspondence,1 Roy et al. report that six among 189 CML patients treated with imatinib at their Institution developed a second malignancy. All of the patients had received interferon-based therapy before beginning imatinib therapy. The study reported that the appearance of second malignancies was potentially in accordance with the incidence of cancer in the French population, with the exception of prostate cancer, which was found in three patients. They reported this incidence to be higher than the expected incidence in a French population.
In November 2004 Novartis performed an epidemiological analysis of second primary malignancies among 9518 patients in our global database treated with imatinib during Novartis sponsored clinical trials as well as spontaneous adverse reports from approximately 124 000 patient years (PY) of treatment (unpublished observations, data on file Novartis). The objective was to compare the incidence rates of second cancers among patients treated with imatinib with the expected incidence based on the rates among the general population. In addition, the frequency of spontaneous reports of cancer associated with imatinib was analyzed based on cases collected in the clinical safety database. This analysis did not provide evidence for an increased overall incidence of malignancies or in the incidence of bladder, kidney or prostate tumors in patients treated with imatinib compared to that of an age adjusted general population.
In May 2005 Novartis updated the information on second malignancies as part of ongoing safety surveillance (unpublished observations, data on file Novartis). In all, 110 malignant neoplasms including 16 prostate ca, two urinary bladder ca and three kidney carcinomas, were reported up to May 10, 2005 in Novartis sponsored clinical trials of imatinib. The observed incidence rates were: 720.34 per 100 000 PY for all malignant cancers (excluding nonmelanoma skin cancer and malignancies representing progression of the underlying disease) and 262.01 per 100 000 PY for prostate cancer. To compare these with the incidence of cancer in the general population, standardized incidence ratios (SIRs) (i.e., ratios of observed to expected cases) standardized for gender and 5-year age groups were estimated, based on Surveillance, Epidemiology, and End Results (SEER) data (Surveillance, Epidemiology and End Results (SEER) Program (http://www.seer.cancer.gov)). The SIRs were 0.87 (95% CI 0.69–1.08) and 0.86 (95% CI 0.49–1.39) for all cancers and prostate cancer, respectively, showing that the numbers of cancers in the Novartis sponsored clinical trials are similar to those expected based on the rates in general population. This database continues to mature with a mean time-at-risk for the trial population of 1.16 years (0–4.91 years), defined as a period starting 4 weeks after the beginning of imatinib until the end of follow-up.
Roy et al. report that each of six patients at their Institution with a second malignancy was at least 60 years old. Specifically, among three patients who developed prostate cancer, two were 65 and one 69 years old. The authors calculated the incidence rate as 478.5 per 100 000 PY, compared it with incidence rates for age group 40–69 in France (region Bas-Rhin) for 1975–1977 (35.0 per 100 000) and for 1995–1997 (110.6 per 100 000) and concluded that the frequency of prostate cancer on imatinib is at least four times higher than expected. As stated in Quaglia et al.2 prostate ca ‘usually affects elderly subjects aged 65 years or more and is a rare disease before 50 years of age’. Incidence rates for prostate carcinoma increase dramatically with age: from 10.4 per 100 000 PY for the age group 40–49, through 118.7 for 50–59, and 507.5 for 60–69 years old men (average annual age-adjusted incidence rates in the US based on year of diagnosis 1992–2001: SEER) (Surveillance, Epidemiology and End Results (SEER) Program (http://www.seer.cancer.gov)). Thus, only a comparison of rates within relatively narrow age groups is scientifically justified. Although the majority of imatinib patients (69%) observed by Roy et al. were between 40 and 69 years old, the differentiation of incidence rates of prostate cancer in this age group precludes any valid comparison.
We would like to congratulate Roy et al. for monitoring their patient populations for ongoing and late side effects of therapy. Given the remarkable success imatinib has had in patients with CML, coupled with the necessity to continue therapy based on current results, we concur with the need for long-term monitoring of patients on imatinib for late effects. They also made reference to the investigator notification letter, which was sent on September 24, 2004 following the preliminary results coming from our 2 year preclinical carcinogenicity study performed in rats. To date, this preclinical information has not translated to a signal, we can detect in patients, but imatinib has been available to patients for less than a decade and close monitoring is called for. In keeping with the Company’s commitment to ensure patient health and safety, Novartis will continue to monitor the long-term effects of treatment with imatinib, such as second malignancies, through ongoing clinical trials, as well as spontaneous reports from researchers and physicians. To date, no increased incidence of prostate cancer or any other type of human malignancy has been detected by Novartis in patients exposed to imatinib.
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References
- Roy L, Guilhot J, Martineau G, Larchee R, Guilhot F. Unexpected occurrence of second malignancies in patients treated with interferon followed by imatinib mesylate for chronic myelogenous leukemia. Leukemia 2005, Jul 14; [E-pub ahead of print].
- Quaglia A, Parodi S, Grosclaude P, Martinez-Gracia C, Coebergh JW, Vercelli M. Differences in the epidemic rise and decrease of prostate cancer among geographical areas in Southern Europe: an analysis of differential trends in incidence and mortality in France, Italy and Spain. Eur J Cancer 2003; 39: 654–665. | Article | PubMed | ISI | ChemPort
Leukemia – Epidemiological analysis of second primary malignancies in more than 9500 patients treated with imatinib: “P R Pilot1, K Sablinska2, S Owen1 and A Hatfield1
1. 1Novartis Pharmaceuticals Corporation, East Hanover,New Jersey, USA
2. 2Novartis Pharma AG, Basel, Switzerland E-mail: Samantha_jane.owen@novartis.com
Reply to Roy et al. Leukemia advance online publication, 14 July 2005. Unexpected occurrence of second malignancies in patients treated with interferon followed by imatinib mesylate for chronic myelogenous leukemia. In their correspondence,1 Roy et al. report that six among 189 CML patients treated with imatinib at their Institution developed a second malignancy. All of the patients had received interferon-based therapy before beginning imatinib therapy. The study reported that the appearance of second malignancies was potentially in accordance with the incidence of cancer in the French population, with the exception of prostate cancer, which was found in three patients. They reported this incidence to be higher than the expected incidence in a French population.
In November 2004 Novartis performed an epidemiological analysis of second primary malignancies among 9518 patients in our global database treated with imatinib during Novartis sponsored clinical trials as well as spontaneous adverse reports from approximately 124 000 patient years (PY) of treatment (unpublished observations, data “
Posted by rob on under Uncategorized |
Senel S, Kaya E, Aydogdu I, Erkurt MA, Kuku I.
Department of Internal Medicine Turgut Ozal Medical Center, Inonu University Faculty of Medicine, 44069, Malatya, Turkey, ssenel@inonu.edu.tr.
We report four patients with rheumatic disease (RD) and chronic myelogenous leukemia (CML). In two patients with Behcet’s disease (BD) and rheumatoid arthritis (RA), CML developed after RD, in two patients with diffuse cutaneous systemic sclerosis and spondyloarthropathy, RD was diagnosed after CML. A variety of interactions have been described between hematological malignancies and RD. Nevertheless, few cases of RD have been documented associated with CML. It is unclear whether the development of CML in patients with RD and RD development after CML occurs by chance alone, is due to the underlying disease, or is facilitated by drugs. Whatever the cause is, it should be kept in mind that CML may develop in the course of RD and RD may be seen in CML patients.
Entrez PubMed
Posted by rob on under Uncategorized |
John Goldman A1 and Myrtle Gordon A2
A1 Hematology Branch, National Heart, Lung and Blood Institute, NIH, Bethesda, MD, USA
A2 Department of Haematology, Imperial College, London, UK
Abstract:
It is generally accepted that allogeneic stem cell transplantation can ‘cure’ chronic myelogenous leukemia (CML), although occasional patients relapse more than 10 years after the transplant procedure. Such cures presumably result from the combined effects of leukemia stem cells (LSCs) of the conditioning regimen and the graft-vs.-leukemia (GvL) effect mediated by donor-derived T lymphocytes. The advent of imatinib has revolutionized the management of patients with CML, but much evidence suggests that it does not eradicate all LSCs, which theoretically remain a potential source of relapse to chronic phase or advanced phase disease. Moreover, sub-clones of Philadelphia-positive cells bearing mutations that code for amino-acid substitutions in the Bcr-Abl kinase domain can be identified in patients receiving treatment with imatinib and are associated with varying degrees of resistance to this agent. In the present review, we postulate that LSCs, similar to their normal counterparts, may alternate between cycling and quiescent modes. In the cycling mode, they may express Bcr-Abl protein and be susceptible to the acquisition of additional mutations, whereas, in the quiescent mode, they may express little or no Bcr-Abl oncoprotein, cannot acquire additional mutations and are unaffected by imatinib. Thus, a patient who starts treatment early in the natural history of CML, and who responds to imatinib clinically, may not have had the opportunity to acquire additional mutations in LSCs. In this case, the persistence long-term of quiescent ‘non-mutated’ LSCs despite imatinib treatment might be consistent with freedom from relapse to chronic or advanced phase disease, provided that they remain vulnerable to imatinib when they are recruited into cycle. Conversely, when imatinib resistant Philadelphia-positive sub-clones predominate, this is likely to be due to the recruitment to hematopoiesis of quiescent stem cells that had been in cycle before administration of imatinib and that had acquired additional mutations; in such cases, the best approach to eradication of residual LSCs might be to target expressed proteins thought to be targets for the GvL effect.
Keywords:
CML, stem cells, SCT, imatinib, mutations
Taylor & Francis Group – Article
Posted by rob on March 5, 2006 under Uncategorized |
by Dale King, Julia Hebert
In Palm Beach County political circles, Blake MacDiarmid gets around.
He is passionate about politics, yet doesn’t aspire to elective office.
But those who do find his assistance most helpful.
MacDiarmid, 39, who calls Delray Beach home, though he also has lived in Maine and California, is one of those tough-to-define people called a political consultant.
“I fell into it,” said MacDiarmid, who has guided the campaigns of Boca Raton Mayor Steven Abrams, Delray Beach Mayor Jeff Perlman and Boynton Beach Mayor Jerry Taylor, among others.
He would have been the consultant for both Boca Raton City Councilman Bill Hager and for M.J. “Mike” Arts, who succeeds incumbent Councilwoman Susan Haynie this year.
But neither is opposed – and no election is needed.
MacDiarmid is working with Fred Fetzer and Brenda Montague, who are running for the Delray Beach City Commission March 14.
This tall, lanky Floridian isn’t consultant-like. He is comfortable in jeans and shorts, enjoys playing with his son, Ian, and spending time with his wife, Dorothy, who he calls “a professional volunteer.” She is president of the Junior League of Boca Raton and serves on the Heart Ball and Palm Beach County Historical Centennial committees.
They are also soul mates with much in common. “She is my rock,” he said of his wife of nearly 13 years. “We met in Delray Beach, we got married and then lived in Mizner Park. We were among the first urban dwellers. I had a consulting business, and she was a senior at Lynn University. She graduated summa cum laude,” he said with pride.
The veteran political consultant said it’s hard to define his job. “It’s the art of taking complicated matters and making them clear and concise for people to understand,” he said.
“Government is not simple,” he said. “And people prefer to live their own lives.” Most don’t have time to delve into such issues as taxes, growth and traffic.”
“I try to make things simple without making them too simple,” he said. “And that’s the challenge – not to make them too simple.”
“People don’t want to hear about politics or politicians,” he noted. “But when they do pay attention, they deserve straight talk.”
MacDiarmid thinks he’s done that. He’s been involved in some four-dozen campaigns – and only two didn’t hit the mark.
Unlike consulting firms, MacDiarmid works alone. “It’s me, my cell phone and my Blackberry. I am truly a mobile professional.”
MacDiarmid attended schools in Gulfstream; St. Andrews High School and Florida Atlantic University, earning a degree in political science. “I went right into politics,” he said. “But I was burned out by age 25.”
“I thought I would go into the family business,” innkeeping,” he said. He did – for a while. In fact, his parents and brother run a family-style, bed-and-breakfast-type inn in Maine.
For the MacDiarmids, 1997 was a critical time. “I was diagnosed with leukemia,” he said. Specifically, Chronic Myelogenous Leukemia.
“I was visiting here for Thanksgiving,” he recalled. And after being diagnosed, he said, “I was told to get my affairs in order.”
The MacDiarmids went to Dana Farber Cancer Institute in Boston – without positive results.
In 1998, they discovered a new drug in San Diego, Calif. It was called Gleevec – and “was one of the first truly targeted DNA drugs.”
He took a couple of years off to recover – and has been in remission for three years.
MacDiarmid is also into sailing – and has become a seaman of note. He skippered his Melges 24 to victory in the San Diego Volvo Leukemia Cup Regatta, beating America’s Cup winner Dennis Connor in the process.
“I remember sitting on the patio overlooking Del Mar and talking to a friend. He said, ‘What are you going to do now?’ He asked me about sailing, and I said I can’t make money sailing.”
So he returned to politics. “We packed up the Suburban and headed back to Palm Beach County.”
Meeting Steven and Debbie Abrams in the mid-1990s helped him get back his political sea legs.
He said he prefers to work on local elections. He has been a consultant for Palm Beach County Commissioners Karen Marcus and Mary McCarty, state Sen. Jeff Atwater, state Rep. Ellen Bogdanoff and U.S. Rep. E. Clay Shaw, to name a few.
Right now, he is working – gratis — for passage of two referendum questions on the March 14 ballot in Boca Raton. One is a pay raise for the mayor and council members; the other a change from two-year to three-years terms for office holders. He said he believes in both – even though the latter will cut into his pay because Boca would not have to hold a municipal election every year.
MacDiarmid admits that he tries to “shut the cell phone off” every now and then to enjoy a private life.
He does in the summer. For eight weeks each year, he sheds his political consultant trappings to run a sailing program in Southport, Maine. It gives him time to relax and reflect – and to share time with 7-year-old son, Ian, a budding filmmaker – and whose knowledge of movies seems bottomless. “He loves to watch the ‘making-of’ segments at the end of DVDs,” said Ian’s dad.
MacDiarmid sees politics coming back into vogue. “Ten years ago, no one knew what a political consultant was,” he said. “Now, they do. And they want to be engaged in politics.”
If anything, the consultant added, politics – and his life — “is never boring.”
Dale M. King can be reached at 561-549-0832 or at dking@bocanews.com.
Boca Raton News – The Leader in Local News Online
Posted by rob on March 4, 2006 under Uncategorized |
BALTIMORE, March 3 (AScribe Newswire) — A mouse immune cell that plays dual roles as both assassin and messenger, normally the job of two separate cells, has been discovered by an international team of researchers from the United States and France. The discovery has triggered a race among scientists to find a human equivalent of the multitasking cell, which could one day be a target for therapies that seek out and destroy cancer.
“In the same way that intelligence and law enforcement agencies can face deadly threats together instead of separately, this one cell combines the ability to kill foreign pathogens and distribute information about that experience,” says Drew Pardoll, M.D., Ph.D., the Seraph Professor of Oncology at the Johns Hopkins Kimmel Cancer Center.
“We think this hybrid cell speeds up immune reactions and makes the system more efficient,” adds Pardoll, whose findings are reported in the February issue of Nature Medicine.
The Hopkins investigators speculate that the hybrid, dubbed “IKDC” for interferon-producing killer dendritic cell, has been missed by cancer biologists because it is rare, making up one-tenth of cells in the spleen with similar features, such as other dendritic cells, according to Frank Housseau, Ph.D., research associate at Hopkins’ Kimmel Cancer Center and member of Pardoll’s immunology laboratory.
Most of the immune system typically works through a web of cross-talk and signaling among a variety of cells. One of the first immune cells that invading bacteria or cancer cells – both of which carry antigens that alert the immune system – may encounter is a natural killer (NK) cell. As its name implies, NK cells deliver a deadly blow by poking holes in the invader’s outer membrane. Then, NK cells secrete molecules that reach other immune cells, including dendritic cells, known as the main messenger for the immune system. Dendritic cells spread “look here” information about foreign invaders to other immune cells, but do not actually kill the invaders.
It was while investigating a particular type of dendritic cell that Housseau noticed the outer membranes of these cells were studded with what were supposed to be hallmarks of NK cells, akin to finding feathers on a dog.
“We thought we were looking at dendritic cells, but we were wrong – they were some type of NK-dendritic cell blend,” says Housseau. The blended cell turned out to be a newly identified actor on the immune system stage that retains all the molecular characteristics of both NK and dendritic cells.
Probing further, Housseau scoured the surface of IKDCs to create a sketch of its molecular profile. He found that it produces both types of interferon proteins, normally secreted independently by NK and dendritic cells. He also found both NK and dendriticlike molecules on the surface of IKDCs. Housseau calculated that they account for about 10 percent of conventional dendritic cells in the spleen.
IKDCs begin their lives behaving like an NK cell. After the cell encounters a pathogen, the cell switches roles from killer to dendriticlike messenger, and, according to the researchers, the swap occurs only once. Then, the cell dies and is replenished by the bone marrow.
“When an IKDC cell switches to its messenger function, the transformation is quite astonishing,” says Pardoll. The cell sprouts long, hairy tentacles called dendrites. It uses its “arms” to increase the amount of surface area it reaches to communicate and interact with other immune cells.
In the next step of their investigation, the scientists tracked the location of fluorescent-tagged IKDCs and their corresponding stage of transformation after infecting mice with bacteria called listeria. In assassin-mode, the IKDCs were found in the blood, lining of the gut, liver and other organs – all areas where there is close contact with environmental pathogens. “Here, IKDCs are ready to sense invaders and spring into action,” says Housseau.
Then, the group tracked the cells to the main messenger center of the immune system – the lymph nodes. Here, they found approximately 35 percent of the original group of IKDCs now secreting communication molecules signaling a switch to messenger-mode.
Simultaneously, Housseau’s colleagues in France, led by Laurence Zitvogel at the Institut Gustave Roussy, tested whether IKDCs are culprits in killing cancer by injecting mice with a cancer drug called Gleevec, which blocks an abnormal protein produced by cancer cells, and a growth factor for NK cells. The drug-growth factor combo served as a lure, leading the IKDCs to tumors implanted in the mice. The results were that tumors shrunk in mice, which received injections of IKDCs, but not in those receiving conventional NK cells only. Evidence from the shrunken tumors revealed certain “cell-killing” proteins that could be traced to IKDCs. These results are published separately in Nature Medicine.
Housseau’s group is conducting further studies to verify the role of IKDC cells in infection and cancer. Meanwhile, the group is profiling IKDC genes to find a specific marker that could help them identify a human counterpart.
The Hopkins research was funded by the National Institutes of Health, the Janney Fund and Seraph Foundation, and gifts from Bill and Betty Topecer and Dorothy Needle.
Participants in the research include Camie W. Chan, Emily Crafton, Hong-Ni Fan, James Flook, Kiyoshi Yoshimura, Mario Skarica, and Monique F. Stins from Johns Hopkins; Dirk Brockstedt and Thomas W. Dubensky from Cerus Corporation; and Lewis L. Lanier from the University of California, San Francisco.
“Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity.” Nature Medicine 12, 167 – 168 (2006).
– - – -
CONTACT: Vanessa Wasta, Johns Hopkins Kimmel Cancer Center Office of Public Affairs, 410-955-1287, wastava@jhmi.edu
VIDEO FOOTAGE AVAILABLE: IKDC cell killing a cancer cell. Courtesy of the Institut Gustave Roussy.
ON THE WEB: http://www.hopkinskimmelcancercenter.org
Media Contact: See above.
Untitled Document
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STUART BATHGATE
SOMETIMES gold medallists retire immediately, eager to quit at the top. Sometimes they hang on to defend their title, and then go if they fail to retain it. Only rarely do they keep coming back time after time – but that is precisely what Ian Marsden will be doing at the Commonwealth Games in Melbourne.
Now 46, Marsden, who competes in the skeet shotgun event, was the gold medallist in Auckland in 1990. Even then he was pretty experienced, having first participated in the Games in 1986, when they were held for the second time in Edinburgh, and having won his first cap for Scotland five years before that.
So he would have been forgiven if he had wanted to bow out at the top, or even four years later when he took bronze in Victoria. Yet he kept going in the most adverse of circumstances.
It was a year or so after the 1998 Games in Kuala Lumpur that Marsden, the manager of a Perthshire estate, was diagnosed with leukaemia. The players and staff at St Johnstone immediately volunteered for blood tests to see if they were suitable bone-marrow donors: the tests proved negative, but the footballers’ gesture was an indication of the support offered by the local community, and Marsden was in no way dismayed. “You have to hold out hope, and as a sportsman I’m using my determination to help stay strong,” he said then.
That determination was vindicated two years later, when treatment with a drug called Gleevec cured him of his potentially fatal condition. Having kept relatively fit throughout his illness, Marsden again represented Scotland in the Commonwealth Games of 2002, held in Manchester.
Twenty years on from his first Games, he is looking forward just as eagerly to competing in Australia as he was back then to shooting in his own country.
“It’s a bit out of season for us, my sport especially, but training has been good and the weather’s been kind recently, so we’re well prepared,” he said. “Shooting is an outdoor sport, so my season is basically April till September.
“It couldn’t be more out of season than we are now, but things are looking well. In the off season we just try to train whenever possible, when the weather suits and the daylight is adequate.”
While he patently has an aptitude for and an enjoyment of shooting, Marsden feels a particular affinity for the competitive environment. Try as he might, he has never quite been able to give of his best in training, which makes it hard to work out exactly what form he might be in.
“I’m the type of animal who is lifted by the event,” he explained. “I probably only function at 95 per cent in training. It’s all very tight. You need to be 100 per cent on form, and you need a bit of luck as well. It’s only one target that will split those medals after 150, so it’s very, very close.
“I wouldn’t say I get nervous, but when the pressure is on I get aware of it. You can’t afford to be blase at that level. Being a shotgun shooter it’s not so vital that I keep absolutely still. It’s a moving game. But you certainly don’t want your knees banging together. That wouldn’t help.”
Something else that does not help is the isolation often imposed on the shooting competition. At the Manchester Games, for instance, the shooting went ahead in Bisley, Oxfordshire; as a result, the publicity it received was considerably less than the other so-called minority sports.
This time, however, is different, and Marsden’s memories of Melbourne make him particularly glad that he and his colleagues will be less detached this time.
“Our venue is about an hour’s drive from the village, which is nearer than Bisley was to Manchester. And previously, in 1998 [in Kuala Lumpur], we were detached as well, because we were on an island. So it will be nice to be back in the main village and feel more attached to the event as a whole.
The relative lack of publicity in the past, however, has never prevented Marsden from feeling under pressure to do well. Some of that comes from within, from his own high standards, but a lot also comes from a general public presumption that Scotland’s shooters will always be good for a couple of medals.
“There is pressure on us here, because we’ve always been very successful at shooting,” he explained. “So there are expectations made of us. It’s a pity that we don’t get the media exposure that some other sports get, but we’ve learned to live with that. We’ll enjoy it just the same.”
And like his team-mates, Marsden will enjoy it all the more because he is representing Scotland. “At world championships you’re always under the GB flag,” he said. “It’s nice to represent Scotland, and this is the highest level under that flag.”
Scotsman.com Sport – Irrepressible Marsden back again
Posted by rob on under Uncategorized |
Mhairi Copland, Ashley Hamilton, Lucy J Elrick, Janet W Baird, Elaine K Allan, Niove Jordanides, Martin Barow, Joanne C Mountford, and Tessa L Holyoake*
Section of Experimental Haematology and Haemopoietic Stem Cells, Division of Cancer Sciences and Molecular Pathology, University of Glasgow, Glasgow, Scotland, United Kingdom
Department of Haematology, Glasgow Royal Infirmary, Glasgow, Scotland, United Kingdom
* Corresponding author; email: tlh1g@clinmed.gla.ac.uk.
Dasatinib (BMS-354825), a novel dual SRC/BCR-ABL kinase inhibitor exhibits greater potency than imatinib mesylate (IM) and inhibits the majority of kinase mutations in IM-resistant chronic myeloid leukaemia (CML). We have previously demonstrated that IM reversibly blocks proliferation, but does not induce apoptosis, of primitive CML cells. Here we have attempted to overcome this resistance with Dasatinib. Primitive IM-resistant CML cells showed only single copy BCR-ABL, but expressed significantly higher BCR-ABL transcript levels and BCR-ABL protein compared to more mature CML cells (p=0.031). In addition CrKL phosphorylation (P-CrKL) was higher in the primitive CD34+38- than the total CD34+ population (P=0.002). In total CD34+ CML cells, IM inhibited phosphorylation of CrKL at 16 but not 72 hours, consistent with enrichment of an IM-resistant primitive population. CD34+38- CML cells proved resistant to IM-induced inhibition of CrKL phosphorylation and apoptosis, whereas Dasatinib led to significant inhibition of CrKL phosphorylation. Kinase domain mutations were not detectable in either IM or Dasatinib-resistant primitive CML cells. These data confirm that Dasatinib is more effective than IM within the CML stem cell compartment, however the most primitive quiescent CML cells appear to be inherently resistant to both drugs.
Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML, but does not eliminate the quiescent fraction — Copland et al., 10.1182/blood-2005-07-2947 — Blood
Posted by rob on under Uncategorized |
Mhairi Copland, Ashley Hamilton, Lucy J Elrick, Janet W Baird, Elaine K Allan, Niove Jordanides, Martin Barow, Joanne C Mountford, and Tessa L Holyoake*
Section of Experimental Haematology and Haemopoietic Stem Cells, Division of Cancer Sciences and Molecular Pathology, University of Glasgow, Glasgow, Scotland, United Kingdom
Department of Haematology, Glasgow Royal Infirmary, Glasgow, Scotland, United Kingdom
* Corresponding author; email: tlh1g@clinmed.gla.ac.uk
