Pic Of The Day
Posted by rob on August 17, 2005 under Uncategorized | 
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Performers dance during the opening ceremony of the Arirang Festival in Pyongyang, capital of North Korea.
Largest Study Of Unrelated Bone Marrow Transplantation For Leukemia Serves As Benchmark
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Together with 16 other institutions in the United States, University of Minnesota researchers led the largest study to date in patients with leukemia and related disorders undergoing bone marrow transplantation from unrelated donors. The study was designed to determine whether one of two general approaches to prevent graft-versus-host-disease (GVHD), a potentially lethal complication, might result in improved survival.
While the trial demonstrated similar survival rates, the study was the most comprehensive to date, evaluating various clinical outcomes, resource utilization, costs, and health quality of life. The study, published in the Aug. 3, 2005 online issue of The Lancet, will likely serve as the benchmark for all future studies in this patient population.
Graft-versus-host-disease is a common complication after bone marrow transplantation in which the immune cells from the donated marrow attack the body of the patient who received the transplant. Severity ranges from mild to life threatening, and the disease and its treatment can have a profound effect on quality of life.
The two primary strategies for preventing GVHD, the removal of T-cells (the cell that causes GVHD) and immunosuppressive drug therapy (suppression of T-cell function), were studied in this trial. While the primary aim of the study was to demonstrate whether one approach might be better than the other in terms of disease-free survival three years after transplantation, the study also systematically compared the incidence of various complications (GVHD, graft failure, therapy-related side effects, disease recurrence) as well as utilization of blood products, nutritional supplementation, number of admissions to the hospital and intensive care unit, hospital costs, and health quality of life.
“While the T-cell depletion approach was very effective in reducing the risk of GVHD, a higher risk of viral infection in general and higher risk of disease recurrence specifically in patients with chronic myelogenous leukemia, eliminated the potential benefit of reduced GVHD,” ,” said John E. Wagner, M.D., professor of pediatrics and scientific director of clinical research, Blood and Marrow Transplantation Program and Stem Cell Institute, and lead author of the study. “Overall, we observed no differences in survival at three years and no appreciable differences in cost or quality of life.”
These results counter what investigators might have guessed and reflect the critical importance of performing large randomized trials. “Prior to this study, colleagues promoting T-cell depletion, like myself, predicted that T-cell depletion would have offered a better chance of survival,” Wagner said. “What is abundantly clear is that T-cell depletion and GVHD prevention is only one step in figuring out how to improve upon the chance of cure in unrelated marrow transplant patients. The next hurdle is to find ways to fix the crippled immune system.”
Despite the lack of evidence that one approach was better than the other, “the results clearly point out the limitations of bone marrow transplants,” Wagner said. However, he added that the methodological approaches used and study results will be valuable benchmarks for future studies of novel treatments for leukemias and other blood-related cancers.
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The study was sponsored by the National Heart, Lung and Blood Institute.
Largest Study Of Unrelated Bone Marrow Transplantation For Leukemia Serves As Benchmark
Structural GenomiX Initiates Phase 2/3 Trial of Troxatyl for the Treatment of Acute Myelogenous Leukemia
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SAN DIEGO, Aug. 16 /PRNewswire/ — Privately held Structural GenomiX,
Inc., (SGX) announced today that the first patient has been enrolled in a
Phase 2/3 clinical trial of Troxatyl(TM), a novel anti-cancer drug candidate
for treatment of acute myelogenous leukemia (AML). The study, with targeted
enrollment of 211 patients at approximately 40 trial centers in the United
States and Europe, is designed to establish the safety and effectiveness of
Troxatyl in patients with relapsed or refractory AML (http://www.clinicaltrials.gov).
Francis Giles, M.D., Chief of Section, Developmental Therapeutics,
Department of Leukemia at the University of Texas M. D. Anderson Cancer
Center, is a Principal Investigator in the study. Dr. Giles commented, “My M.
D. Anderson Cancer Center colleagues and I are very excited to be playing a
leadership role in the clinical development of Troxatyl for treatment of AML.
Our initial clinical studies and additional recent work with this novel
investigational agent have demonstrated considerable promise for treatment of
both AML and myelodysplastic syndromes, for which there are significant unmet
medical needs. Among those needs, none are more pressing than in third-line
treatment of AML. We are delighted to have a study focused on this very
refractory population open for enrollment of our patients.”
The patients targeted in this Phase 2/3 study are those who are in second
relapse with duration of second response less than 6 months, or who were
refractory to two previous courses of induction chemotherapy.
About Troxatyl
Troxatyl, a nucleoside analog, represents the first member of a new class
of anti-cancer agents. Its unique chemical structure confers potential
advantages compared to existing AML therapy in that it is not subject to
common deactivating mechanisms that can cause resistance to existing therapy.
In preclinical studies, Troxatyl has demonstrated broad activity against both
solid tumors and hematologic malignancies. To date, approximately 700
patients have been treated in various Troxatyl Phase 1 and 2 studies in which
delivery of the drug was by bolus intravenous (IV) injection. Promising early
clinical results were observed in AML, myelodysplastic syndromes, blast phase
chronic myelogenous leukemia, renal cell carcinoma, and pancreatic cancer when
Troxatyl was administered via bolus IV injection.
Recent preclinical work has shown that Troxatyl administered as a
continuous IV infusion (CI) over 4 or 5 days results in significantly
increased drug exposure to the cancer cells. A presentation of data at ASCO
from a recently completed Phase 1/2 CI study of AML patients, most of whom had
failed multiple chemotherapy regimens and in some cases bone marrow
transplantation, reported an overall response rate of 19 percent. Moreover,
the study demonstrated that a 50 percent greater dose of Troxatyl may be
safely administered via continuous infusion compared to the bolus IV injection
route. The presentation also reported that the responding patients had a
median duration of response greater than 7 months. In this setting, Troxatyl
had a manageable and transient toxicity profile and was well tolerated, even
in patients over the age of 60 who are typically less tolerant of existing
therapies than younger patients. A Phase 1/2 CI study in solid tumors is
currently enrolling pancreatic cancer patients (http://www.clinicaltrials.gov).
About AML
AML is a hematopoietic stem cell disorder that is the most common form of
acute leukemia, accounting for 80 to 90 percent of all acute leukemias in
adults. Although standard induction chemotherapy results in complete
remission in 50 to 75 percent of patients, relapse is common and long-term
survival rates remain at approximately 20 percent. At present, patients with
relapsed or refractory AML have limited treatment options, underscoring the
need for new drugs in this challenging therapeutic area. A recently published
review of M. D. Anderson’s historical experience with third-line therapy for
AML patients reports a less than 5 percent overall response rate with a 1 to 2
month average life expectancy, underscoring the unmet need in this patient
setting.
About SGX
SGX is a biotechnology company focused on the discovery and development of
innovative cancer therapeutics. SGX’s lead product candidate is Troxatyl, a
novel cancer therapeutic currently in Phase 2/3 clinical trials for the
treatment of Acute Myelogenous Leukemia and in Phase 1/2 clinical trials for
the treatment of various solid tumors. SGX has also developed a preclinical
pipeline of novel oncology therapeutics using SGX FAST(TM) technology, a
proprietary fragment-based approach to lead generation. The SGX preclinical
oncology pipeline comprises novel inhibitors of the Gleevec resistant BCR-ABL
(including T315I) mutant and dual specificity inhibitors of the MET-RON
receptor tyrosine kinases. SGX is also pursuing a broad program of
fragment-based lead generation directed against a portfolio of validated
oncology targets that include HSP-90 and the Aurora kinases. SGX has secured
revenue generating drug discovery and development partnerships with leading
pharmaceutical and biotechnology companies including Eli Lilly, Serono S.A.,
and Roche. For more information, please visit the company website at
http://www.stromix.com.
Forward-Looking Statements
This press release contains forward-looking statements, including those
relating to SGX’s plans regarding a Phase 2/3 clinical trial of Troxatyl(TM)
and to advance Troxatyl(TM) for the treatment of AML. The clinical
development of investigational pharmaceutical products is subject to risks and
uncertainties. There can be no assurance that SGX’s investigational studies
of any of its product candidates can be conducted within the time frame that
the company expects, or that the studies will yield positive results. There
can be no assurance that future clinical trials will confirm the preliminary
results referred to in this release or that Troxatyl(TM) will receive
regulatory approvals or prove to be commercially successful. For further
discussion of these and other risks and uncertainties, see the various
disclosures made by SGX. SGX undertakes no duty to update forward-looking
statements.
Zoledronate synergises with imatinib mesylate to inhibit Ph primary leukaemic cell growth.
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Segawa H, Kimura S, Kuroda J, Sato K, Yokota A, Kawata E, Kamitsuji Y, Ashihara E, Yuasa T, Fujiyama Y, Ottmann OG, Maekawa T
Br J Haematol. 2005 Aug ; 130(4): 558-60
Summary We examined the in vivo effects and safety of the third generation bisphosphonate, zoledronate (ZOL) alone and combined with imatinib mesylate against primary Philadelphia chromosome positive (Ph(+)) leukaemic cells. ZOL inhibited the prenylation of Rap1A in leukaemic cells in vitro and synergised with imatinib to enhance the survival of mice engrafted with cells from imatinib-responders, but not from non-responders because of mutated BCR-ABL. These findings suggest that the combination of ZOL and imatinib accelerate the eradication of Ph(+) clone, resulting in better prognosis of Ph(+) leukaemia patients who have not yet acquired mutations.
Zoledronate synergises with imatinib mesylate to inhibit Ph primary leukaemic cell growth.
Investigation of the Bovine Leukemia Virus Proviral DNA in Human Leukemias and Lung cancers in Korea.
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Lee J, Kim Y, Kang CS, Cho DH, Shin DH, Yum YN, Oh JH, Kim SH, Hwang MS, Lim CJ, Yang KH, Han K
J Korean Med Sci. 2005 Aug ; 20(4): 603-6
The bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis. This study investigated the presence of the BLV in leukemia (179 acute lymphoblastic leukemia, 292 acute myeloid leukemia and 46 chronic myelogenous leukemia cases) and 162 lung cancer patients (139 adenocarcinoma, 23 squamous cell carcinoma) to determine if the BLV is a causative organism of leukemia and lung cancer in Koreans. A BLV infection was confirmed in human cells by PCR using a BLV-8 primer combination. All 517 cases of human leukemia and 162 lung cancer were negative for a PCR of the BLV proviral DNA. In conclusion, although meat has been imported from BLV endemic areas, the BLV infection does not appear to be the cause of human leukemia or lung cancer in Koreans. These results can be used as a control for further studies on the BLV in Koreans.