Posted by rob on April 1, 2011 under Uncategorized | 
ConclusionsDaily oral imatinib at a dose of 340?mg/m2 is well tolerated in children. In addition, imatinib therapy is effective in inducing a high percent of hematologic, cytogenetic and molecular responses, comparable to adults with CML. (This study was registered at ClinicalTrials.gov under identifier NCT00030394.) Pediatr Blood Cancer © 2011 Wiley?Liss, Inc. (Source: Pediatric Blood and Cancer)
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Hematopoietic stem cell transplantation (HSCT) is effective therapy for patients with chronic myelogenous leukemia (CML) but is now mostly indicated for patients who develop resistance to tyrosine kinase inhibitors (TKIs), which can be associated with point mutations in BCR-ABL1. We reviewed the outcomes of imatinib-resistant CML patients (chronic phase, n = 34; accelerated phase [AP], n = 9; and blast phase [BP], n = 4) who underwent HSCT and had BCR-ABL1 sequencing. Mutations were found in 19 patients (40%); 15 of 19 had advanced CML (AP + BP + second chronic phase). Patients with mutations were more likely to transform to AP/BP at time of imatinib failure (69% vs 35%, P = .03). Forty-two patients (89%) responded to HSCT: 32 (68%) had at least a major molecular response. The 2-year event…
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In theory, it sounds straightforward: Find genetic mutations essential to the growth and survival of the cancer, identify specific inhibitors in the lab, and validate them in human studies. In practice, it is often a complicated path from mutation discovery to a viable targeted therapeutic agent, said Levi Garraway, MD, PhD (DFCI). Several years ago, for example, failure of the first drug in clinical trials designed to block molecular drivers of metastatic melanoma made the BRAF mutation seem a dubious target. And despite last year?s striking results in early phase trials, it seems clear that inhibiting mutant BRAF activity alone cannot eradicate melanoma tumors nor even hold them back for long. ?The good news is that the other kinases in the pathway remain a hot area for drug discovery,…
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It is daunting for even the most dedicated scholar of cancer research to track the alphabet soup of promising molecular targets and pathways. But last year a BRAF mutation joined the handful of oncogenes that can be therapeutically targeted by a selective inhibitor. Researchers reported a striking regression of metastatic melanoma tumors.?A major breakthrough,? said an editorial in the New England Journal of Medicine (NEJM), titled ?Melanoma?An Unlikely Poster Child for Personalized Cancer Therapy.? The editorial was published in August alongside the phase I results of one of the experimental inhibitors (RG7204/PLX4032, Roche) by Keith Flaherty, MD (MGH) and his co-investigators.In the trial, 81 percent of the 32 patients in the extension cohort (whose cancers carried the signature BR…
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It is daunting for even the most dedicated of scholars to track the alphabet soup of promising molecular targets and pathways. But last year a BRAF mutation joined the handful of oncogenes that can be therapeutically targeted by a selective inhibitor. Researchers reported a striking regression of metastatic melanoma tumors.?A major breakthrough,? said an editorial in the New England Journal of Medicine (NEJM). The editorial, ?Melanoma?An Unlikely Poster Child for Personalized Cancer Therapy,? was published in August alongside the phase I results of one of the experimental inhibitors (RG7204/PLX4032, Roche) by Keith Flaherty, MD (MGH) and his co-investigators.In the trial, 81 percent of the 32 patients in the extension cohort (whose cancers carried the signature BRAF mutation) saw a te…
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Abstract As of 2011, the choice of tyrosine kinase inhibitor (TKI) for the patient with newly diagnosed chronic-phase chronic myelogenous
leukemia (CP-CML) is no longer limited to imatinib but can be expanded to include nilotinib and dasatinib. Since 2000, imatinib
has demonstrated remarkable efficacy in the majority of chronic-phase patients. Nilotinib and dasatinib, both more potent
TKIs, are likely to produce quicker and deeper molecular responses, but there are no established criteria for choosing the
best inhibitor for each patient. We now need to establish clearly defined recommendations to address this new stage, in which
individualized therapy in the front-line should become a reality. Likely to be paramount in this setting are assays that directly
assess the effic…
MedWorm Message: Find out about the Doctors 2.0 and You conference in Paris, June 22-23rd. The call is now on for posters and the start-up contest.
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SummarySweet syndrome (acute febrile neutrophilic dermatosis) is characterized by a dramatic onset of high fever, neutrophilia and typical skin lesions. About 20 % of patients have an associated malignancy, most commonly hematologic diseases. Chronic and paucisymptomatic manifestations of Sweet syndrome may be misdiagnosed or misinterpreted as harmless, resulting in delayed diagnosis. “Atypical” manifestations are especially suspicious for associated malignancies. This is demonstrated by a 39?year old patient with chronic and afebrile disease who was referred to our clinic only after symptoms had persisted for several months. By that point, an underlying nodular lymphocyte predominant Hodgkin’s lymphoma had already reached an advanced stage. Skin biopsies revealed dermal infiltrates …
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Nucleostemin (NS) is a nucleolar-nucleoplasmic shuttle protein that regulates cell proliferation, binds p53 and Mdm2, and is highly expressed in tumor cells. We have identified NS as a target of oxidative regulation in transformed hematopoietic cells. NS oligomerization occurs in HL-60 leukemic cells and Raji B lymphoblasts that express high levels of c-Myc and have high intrinsic levels of reactive oxygen species (ROS); reducing agents dissociate NS into monomers and dimers. Exposure of U2OS osteosarcoma cells with low levels of intrinsic ROS to hydrogen peroxide (H2O2) induces thiol-reversible disulfide bond-mediated oligomerization of NS. Increased exposure to H2O2 impairs NS degradation, immobilizes the protein within the nucleolus, and results in detergent-insoluble NS. The regulation…
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The transcription factor STAT5 is an essential mediator of the pathogenesis of chronic myelogenous leukemia (CML). In CML, the BCR/ABL fusion kinase causes the constitutive activation of STAT5, thereby driving the expression of genes promoting survival. BCR/ABL kinase inhibitors have become the mainstay of therapy for CML, although CML cells can develop resistance through mutations in BCR/ABL. To overcome this problem, we used a cell-based screen to identify drugs that inhibit STAT-dependent gene expression. Using this approach, we identified the psychotropic drug pimozide as a STAT5 inhibitor. Pimozide decreases STAT5 tyrosine phosphorylation, although it does not inhibit BCR/ABL or other tyrosine kinases. Furthermore, pimozide decreases the expression of STAT5 target genes and induces ce…
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Patients with chronic myelogenous leukemia (CML) treated with imatinib who remain in complete cytogenetic remission for 2 years have survival rates comparable to the general population. Medscape Medical News (Source: Medscape Today Headlines)
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Patients taking imatinib (Gleevec) for CML, or chronic myelogenous leukemia, and in remission after two years of treatment, have a mortality rate similar to that of the general population, according to a new study. The article offers the first evidence that a disseminated cancer, not amenable to surgery, can be controlled to the point of giving patients a normal life expectancy. (Source: ScienceDaily Headlines)
MedWorm Message: Find out about the Doctors 2.0 and You conference in Paris, June 22-23rd. The call is now on for posters and the start-up contest.
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Patients taking imatinib (Gleevec) for CML, or chronic myelogenous leukemia, and in remission after two years of treatment, have a mortality rate similar to that of the general population according to a study published online March 22 in the Journal of the National Cancer Institute. The article offers the first evidence that a disseminated cancer, not amenable to surgery, can be controlled to the point of giving patients a normal life expectancy… (Source: Health News from Medical News Today)
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(Journal of the National Cancer Institute) Patients taking imatinib (Gleevec) for CML, or chronic myelogenous leukemia, and in remission after two years of treatment, have a mortality rate similar to that of the general population according to a study published online March 22 in the Journal of the National Cancer Institute. The article offers the first evidence that a disseminated cancer, not amenable to surgery, can be controlled to the point of giving patients a normal life expectancy. (Source: EurekAlert! – Cancer)
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Conclusions Histopathologic analysis is not useful as a routine diagnostic tool in EM because no morphological changes are specific to EM. The capillary proliferation and vasculopathy are assumed to be a consequence of intermittent skin hypoxia (vascular hypothesis of pathogenesis). Whether the proliferation is a consequence of EM or a pathogenic factor in the development of the disease is uncertain. (Source: Archives of Dermatology)
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Conclusion:
The present analysis documents the efficacy of RT. In addition, RT as a palliative treatment option for symptomatic SM should
not be forgotten.
Content Type Journal ArticlePages 1-4DOI 10.1007/s00066-011-2252-4Authors
Jan Kriz, Department of Radiation Oncology, University of Cologne, Cologne, GermanyOliver Micke, Department of Radiation Oncology, St. Franziskus Hospital, Bielefeld, GermanyFrank Bruns, Department of Radiation Oncology, Medical School Hannover, Hannover, GermanyUwe Haverkamp, Department of Radiology and Radiation Oncology, Clemens Hospital Münster, Münster, GermanyRalph Mücke, Department of Radiation Oncology, Hospital Lippe, Lippe, GermanyUlrich Schäfer, Department of Radiation Oncology, Hospital Lippe, Lippe, GermanyHeinrich Seegens…
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The relative merits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and imatinib for chronic myelogenous leukemia in the accelerated phase (AP-CML) have not previously been evaluated. This cohort study was designed to compare the outcomes of imatinib (n = 87) versus allo-HSCT (n = 45) for AP-CML. A multivariate analysis of the total population revealed that a CML duration ≥ 12 months, hemoglobin < 100 g/L, and peripheral blood blasts ≥ 5% were independent adverse prognostic factors for both overall survival (OS) and progression-free survival (PFS). Both treatments resulted in similar survival in low-risk (no factor) patients, with 6-year event-free survival (EFS), OS, and PFS rates of more than 80.0%. Intermediate-risk (any factor) patients showed no difference i…
MedWorm Message: Find out about the Doctors 2.0 and You conference in Paris, June 22-23rd. The call is now on for posters and the start-up contest.
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We describe a novel approach to targeting key proteins in CML cells with a ubiquitin-cycle inhibitor, WP1130. Bcr-Abl is rapidly modified with K63-linked ubiquitin polymers in WP1130-treated CML cells, resulting in its accumulation in aggresomes, where is it unable to conduct signal transduction. Induction of apoptosis because of aggresomal compartmentalization of Bcr-Abl was observed in both imatinib-sensitive and -resistant cells. WP1130, but not Bcr-Abl kinase inhibitors, directly inhibits Usp9x deubiquitinase activity, resulting in the down-regulation of the prosurvival protein Mcl-1 and facilitating apoptosis. These results demonstrate that ubiquitin-cycle inhibition represents a novel and effective approach to blocking Bcr-Abl kinase signaling and reducing Mcl-1 levels to engage CML …
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Donor lymphocyte infusion (DLI), whereby donor mononuclear cells are infused into patients, is one of the few effective immunotherapeutic strategies that generate long-lasting tumor remissions. We previously demonstrated that chronic myelogenous leukemia (CML) patients treated with DLI develop high-titer plasma antibodies specific for CML-associated antigens, the majority of which have been reported to bind nucleic acids These observations led us to predict that circulating antibody-antigen complexes in DLI-responsive patients carry nucleic acids that can engage innate immune sensors. Consistent with this, we report here that post-DLI plasma from 5 CML patients that responded to DLI treatment induced massive upregulation of MIP-1α, IP-10, and IFN-α in normal blood mononucle…
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Updated NCCN guidelines for chronic myelogenous leukemia (CML) name the second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib as front-treatment for CML. Medscape Medical News (Source: Medscape Today Headlines)
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Second generation tyrosine kinase inhibitor (TKI) therapies approved for first-line therapy of chronic myelogenous leukemia (CML) offer newly diagnosed patients an expanded range of treatment options, according to Susan O’Brien, MD, of The University of Texas MD Anderson Cancer Center and chair of the NCCN Guidelines™ for CML. Dr. O’Brien emphasized the considerable advances made in the treatment of CML during her presentation of the updated NCCN Guidelines for CML at the NCCN 16th Annual Conference on March 11, 2011… (Source: Health News from Medical News Today)
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