Posted by rob on January 9, 2012 under Uncategorized | 
A compound produced from fish oil that appears to target leukemia stem cells could lead to a cure for the disease, according to Penn State researchers. The compound — delta-12-protaglandin J3, or D12-PGJ3 — targeted and killed the stem cells of chronic myelogenous leukemia, or CML, in mice, said Sandeep Prabhu, associate professor of immunology and molecular toxicology in the Department of Veterinary and Medical Sciences. The compound is produced from EPA — Eicosapentaenoic Acid — an Omega-3 fatty acid found in fish and in fish oil, he said… (Source: Health News from Medical News Today)
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Conclusions.-Validation of laboratory-developed quantitative molecular tests requires careful planning and execution to adequately address all required analytic performance parameters. How these are addressed depends on the potential for technical errors and confidence required for a given test result. We demonstrate how one laboratory validated and clinically implemented a quantitative BCR-ABL1 assay that can be used for the management of patients with chronic myelogenous leukemia.
PMID: 22208485 [PubMed - in process] (Source: Archives of Pathology and Laboratory Medicine)
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Authors: Bates SE, Amiri-Kordestani L, Giaccone G
Abstract
A British humorist said, “There is much to be said for failure. It is much more interesting than success.” This CCR Focus section is aimed at identifying lessons to be learned from difficulties encountered in recent years during development of anticancer agents. Clearly, we have not found a silver bullet tyrosine kinase inhibitor against solid tumors comparable with imatinib in chronic myelogenous leukemia. Although vemurafenib for B-Raf-mutated melanoma and crizotinib for non-small cell lung cancers with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements were developed rapidly and offer hope for individualized targeted therapies, the development of agents targeting a num…
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Abstract Chronic myelogenous leukemia (CML) is a common myeloproliferative disease that is characterized by the clonal expansion of
marrow stem cells, and is associated with the Philadelphia chromosome. As the disease progresses, additional chromosome abnormalities may arise. The prognostic impact of secondary
chromosomal abnormalities in CML is complex, heterogeneous, and sometimes related to previous treatment. Here, we describe
a CML patient in lymphoid blast crisis associated with a new chromosomal abnormality identified, dic(7;12)(p12.21;p12.2) and
i(12)(q10) using classical cytogenetics and spectral karyotype analysis. To the best of our knowledge, this is the first report
of t(7;12)(p11.1;q11.1) and i(12)(q10) in a CML patient with lymphoid evolution.
Content Ty…
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Authors: Holstein SA, Hohl RJ
Abstract
Approval of agents for the treatment of cancers by the US Food and Drug Administration (FDA) was granted to only six new chemical entities in the three years spanning 2008 to 2010. By contrast, in the first nine months of 2011, six new chemical entities were approved for use in cancer. This approval rate is unprecedented and reflects the advances in science since the approval of the first monoclonal antibody (rituximab) in 1997 and the first targeted small-molecule tyrosine kinase inhibitor (imatinib) in 2001 for non-Hodgkin’s lymphoma and chronic myelogenous leukemia, respectively. Here we briefly discuss the newly approved agents, a possible deletion from the therapeutic armamentarium, and the use of the FDA accelerated approval process.
…
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Targeting cancer stem cells is of paramount importance in successfully preventing cancer relapse. Recently, in silico screening of public gene-expression datasets identified cyclooxygenase-derived cyclopentenone prostaglandins (CyPGs) as likely agents to target malignant stem cells. We show here that 12-PGJ3, a novel and naturally produced CyPG from the dietary fish-oil -3 polyunsaturated fatty acid eicosapentaenoic acid (EPA; 20:5) alleviates the development of leukemia in 2 well-studied murine models of leukemia. IP administration of 12-PGJ3 to mice infected with Friend erythroleukemia virus or those expressing the chronic myelogenous leukemia oncoprotein BCR-ABL in the hematopoietic stem cell pool completely restored normal hematologic parameters, splenic histology, and enhanced surviva…
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Abstract The BCR/ABL-negative myeloproliferative neoplasms (MPNs) of essential thrombocythemia, polycythemia vera, and primary myelofibrosis,
over the natural course of their disease, have an increasing predisposition to transform to overt acute myeloid leukemia (AML)—most
appropriately referred to as MPN-blast phase (MPN-BP). Although this transformation is a rare event, once AML has occurred,
it is associated with a poor response to therapy and short survival. The molecular events leading to transformation are poorly
defined. Currently, no therapy other than allogeneic stem cell transplantation (ASCT) has been demonstrated to alter the natural
history of this disease. Multiple therapeutic investigations are currently ongoing, including early ASCT, hypomethylating
agent…
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Cancer researchers studying genetic mutations that cause leukemia have discovered a connection to the rare disease cherubism, an inherited facial bone disorder in children. The link is the enzyme Tankyrase and its pivotal role in switching on or off the protein that controls two known cancer genes. In normal cells, the protein is vital for bone development. In abnormal cells, it is thought to be involved in two common types of blood cancer – chronic myelogenous leukemia and acute myeloid leukemia. The findings, published online today in CELL (DOI: 10.1016/j.cell.2011.10… (Source: Health News from Medical News Today)
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Abstract Imatinib is a powerful protein tyrosine kinase (PTK) inhibitor that specifically targets BCR-ABL, KIT, and PDGFR kinases,
has become the current first-line therapy for all newly diagnosed chronic myeloid leukemia (CML). Beside PTKs, PTK inhibitors
alter the activity of a large number of voltage-dependent ion channels. hERG1 K+ channels are highly expressed in leukemia cells and appear of exceptional importance in favoring leukemogenesis. The present
study explored a possible regulatory effect of imatinib upon hERG1 K+ channels as a means to uncover new molecular events involved in the antileukemic activity of this PTK inhibitor in CML. The
results demonstrated that hERG1 was highly detected in K562 cells and primary CML cells, and down-regulated by imatinib at
mRNA…
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CONCLUSIONS:BCR?ABL1 expression up?regulated HO?1, a survival factor for CML cells. This up?regulation was more pronounced in blast crisis CML relative to early stage disease and was mediated by the NADPH oxidase components Rac1 and p47phox. The expression of p47phox was increased in BCR?ABL1–expressing cells. Cancer 2011. © 2011 American Cancer Society. (Source: Cancer)
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Conclusions Our data suggest the potential usefulness of DOK2 as a marker of poor prognosis in patients with gastric cancer after curative
resection.
Content Type Journal ArticleCategory Gastrointestinal OncologyPages 1-8DOI 10.1245/s10434-011-2157-6Authors
Hiromichi Miyagaki, Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, JapanMakoto Yamasaki, Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, JapanTsuyoshi Takahashi, Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, JapanYukinori Kurokawa, Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, JapanHiroshi Miyata, Department of Gastroent…
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In this study, we found that treatment with ABL kinase inhibitors or depletion of BCR-ABL induced the expression of RAB45 messenger RNA and protein and induced apoptosis via reduction of mitochondrial membrane potential and p38 activation in CML cell lines and BCR-ABL+ progenitor cells from CML patients. Overexpressed RAB45 induced the activation of caspases-3 and -9 and reduced the expression of Survivin, XIAP, c-IAP1 and c-IAP2 in CML cells. Moreover, in colony-forming cells derived from CML-aldehyde dehydrogenasehi/CD34+ cells, treatment with ABL kinase inhibitors induced RAB45 expression and reduced mitochondrial membrane potential, resulting in inhibited colony formation of Bcr-Abl+ progenitor cells. The overexpression of RAB45 significantly decreased colony numbers and induced apopto…
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During the week I graduated from high school, my mother was diagnosed with chronic myelogenous leukemia (CML). Today, patients with CML are treated with imatinib and do remarkably well, but at the time, there was no effective treatment available and my mother passed away three years later. Watching her battle with cancer spurred my interest in medical research. I currently study pancreatic cancer.
read more (Source: Stand Up 2 Cancer)
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Imatinib mesylate treatment markedly reduces the burden of leukemia cells in chronic myelogenous leukemia (CML) patients. However, patients remain at risk for relapse on discontinuing treatment. We have previously shown that residual BCR-ABL+ progenitors can be detected in CML patients within the first 2 years of imatinib treatment. However, reduced rates of relapse and continued decline of BCR-ABL levels with prolonged treatment, together with the ability of selected patients to maintain remission after discontinuing treatment, led us to investigate whether prolonged imatinib exposure resulted in reduction or elimination of BCR-ABL+ stem cells. We evaluated BCR-ABL expression in CD34+CD38+ (38+) committed progenitors and CD34+CD38– (38–) stem/primitive progenitor cells in samp…
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Authors: Serpa M, Sanabani SS, Dorlhiac-Llacer PE, Nardinelli L, de Barros Ferreira P, Borges Martins TF, Seguro F, Bendit I
Abstract
Despite the beneficial effects of imatinib mesylate, some patients may either not respond or respond suboptimally. Here, we report two chronic myelogenous leukemia patients; one had a suboptimal response according to European LeukemiaNet criteria (a major molecular response was not achieved after 18 months of standard-dose imatinib therapy) and the other had failure with a standard dose of imatinib. At the time of the suboptimal response in patient 1 and the failure in patient 2, we were able to detect the F359I mutation in the BCR-ABL tyrosine kinase domain using DNA sequencing in both patients. Therefore, it was decided to change the therapeutic re…
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AbstractDisease overview: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by stem cell?derived clonal myeloproliferation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival.Diagnosis: Diagnosis is based on bone marrow morphology. The presence of fibrosis, JAK2/MPL mutation or +9/13q? cytogenetic abnormality is supportive but not essential for diagnosis. Prefibrotic PMF mimics essential thrombocythemia in its presentation and the distinction is prognostically relevant. Differential diagnosis of myelofibrosis should include chronic myelogenous leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute my…
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Conclusions Aberrant MAPK-activation triggered by ABL-inhibitors and positively regulated by BCR-ABL kinase mutation T315I might be an
experimental explanation for the clinical observation that patients carrying high-resistance mutations show a highly aggressive
course of their disease when tyrosine kinase inhibitor treatment is not discontinued in time.
Content Type Journal ArticleCategory Original PaperPages 1-10DOI 10.1007/s00432-011-1086-xAuthors
Nicolai Härtel, III. Medizinische Universitätsklinik, Universitätsmedizin Mannheim der Universität Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, GermanyThomas Klag, Klinik f. Innere Medizin II, Abt. f. Hämatologie/Onkologie, Universitätsklinikum Jena, Erlanger Allee 101, 07740 Jena, GermanyBenjamin Hanfstei…
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Abstract:? Porokeratosis is a rare disorder of epidermal keratinization that is regarded as a precancerous. Recipients of hematopoietic stem cell transplantation (HSCT) have a greater risk of skin cancer; chronic graft versus host disease (GVHD) is an additional risk factor. A 16?year?old boy who had received HSCT for acute myelogenous leukemia was referred to us for sclerodermoid chronic cutaneous GVHD. Two years later, he developed disseminated porokeratosis with a few atypical lesions. Despite cryotherapy, numerous lesions of porokeratosis recurred rapidly. Acitretin resulted in good clinical response and reduced the rate of onset of new lesions. (Source: Pediatric Dermatology)
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Damien Reynaud, Eric Pietras, Keegan Barry-Holson, Alain Mir, Mikhail Binnewies, Marion Jeanne, Olga Sala-Torra, Jerald P. Radich, Emmanuelle Passegué. Using a mouse model recapitulating the main features of human chronic myelogenous leukemia (CML), we uncover the hierarchy of leukemic stem and progenitor cells contributing to disease pathogenesi…. (Source: Cancer Cell)
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A 56-year-old woman with diabetic retinopathy and chronic myelogenous leukemia had phacoemulsification cataract removal and hydrophilic acrylic intraocular lens (IOL) (Akreos MI-60) implantation in both eyes. One month after surgery, significant IOL opacity and severe cystoid macular edema were observed in both eyes. After bilateral intravitreal injection of bevacizumab (Avastin) to control macular edema, central clearing of the IOL opacity was observed in both eyes. Two months after the injection, the IOL opacity had almost disappeared from both eyes. To our knowledge, this is the first case of early postoperative bilateral IOL opacity in a hydrophilic acrylic IOL cleared after anti-vascular endothelial growth factor (VEGF) intravitreal injection. The role of anti-VEGF therapy in clearing…
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