Posted by rob on November 22, 2004 under Uncategorized | 
Summary Hydroxyurea (HU) is commonly used for the treatment of chronic myelogenous leukaemia, polycythemia vera and essential thrombocythaemia. Patients receiving HU present a number of side-effects including skin/mucosa changes and tumours. Mucocutaneous abnormalities include xerosis, ichthyosiform lesions, dark brown pigmentation of skin folds and nails, malleolar ulcers, oral mucositis and oral ulcers. Cutaneous squamous/basal cell carcinomas have also often been reported following long-term administration of HU. HU-induced carcinogenesis is due to both the mutagenic potential of this agent and to an impairment of DNA repair mechanisms after damage by external factors such as ultraviolet radiation. Oral cancer following long-term treatment with HU has been reported only once, in a patient with concomitant multiple skin tumours. We present the unique case of a patient with polycythemia vera who developed oral cancer after 15 years of HU therapy.
http://www.hubmed.org/display.cgi?issn=03076938;uids=15550132
Posted by rob on under Uncategorized |
Japanese Fumie Suguri takes part in the gala dance at the end of the Trophy Bompard at the Palais-Omnisports in Paris.
Posted by rob on under Uncategorized |
Swiss pharmaceuticals giant Novartis AG on Thursday reported a 21 percent rise in third-quarter net profit to US$1.55 billion (euro1.26 billion).
http://www.forbes.com/associatedpress/feeds/ap/2004/10/21/ap1601679.html
Posted by rob on under Uncategorized |
Organizers Needed For CML Local Support Group Meetings
With the launch of the new site
http://CMLHope.Com we will now start to expand
the international network of local CML meetings
http://cml.meetup.comThe new system that has been put in place will allow local meetings to
be set up in nearly any city in over 60 countries on a zip code/postal
code basis. Some of you have already volunteered to be the local
CML organizer for your community and we need others to volunteer
to do so.
The new system allows you to control the web page for your local meeting
which can be fully customized and you can choose the location, date,
and time as well as customize by uploading photos of your meeting. Some
have already started customizing their local meeting sites. I have copied
below the Minneapolis local meeting which has customized their local web
site with photos from their recent meetings.
You can apply to become the local CML organizer in your community at
http://cml.meetup.com If there is not a local CML meeting in your community
you can create one at
http://cml.meetup.com/create/ The new Media section
on the web site at CMLHope.Com will allow you to contact local media in any
state in the United States through letters to the editor or press releases to let
others know about your local meeting. There is also ad copy for flyers, etc. on
the Meetup site that can be printed out and placed in appropriate places in your
community.
It also would be good if some would be interested in setting up Meetup groups at
some of the major CML centers such as M.D. Anderson, OHSU, etc. These could
be set up so that patients who regularly go to some of the major centers could get
together in person when they are there on the same days. Other types of social
events can be set up as well such as regional get togethers.
The network of local meetings will allow many more people to be reached but we
need your help to do so. I hope many of you will consider volunteering to be a local
CML organizer. If you need any assistance contact me at
rob@cmlhope.com
Rob
Example Of How Minneapolis Set Up Their Local Meetup Site
Minneapolis Chronic Myelogenous Leukemia Meetup Group
Chronic Myelogenous Leukemia Meetup Group No. 5
Minneapolis, MN
9 members
Next Meetup: Tuesday, Dec 14, 7:00 PM
An opportunity to meet other CML survivors to share stories and experiences in coping with CML and its treatment.
Posted by rob on under Uncategorized |
A Christmas tree made of wine glasses containing fish is displayed at the Aqua Museum in the Hakkeijima Sea Paradise in Yokohama, some 30 kilometre south of Tokyo.
Posted by rob on November 20, 2004 under Uncategorized |
Chilean riot police huddle behind a wall at a street corner in downtown Santiago during clashes with protesters against the Asia-Pacific Economic Cooperation
Posted by rob on November 19, 2004 under Uncategorized |
An Ecuadoran soccer fan applies makeup in the national colors shortly before the South American World Cup qualifying match vs Brazil in Quito.
Posted by rob on under Uncategorized |
Oncogene. 2004 11 15;
Vey N, Mozziconacci MJ, Groulet-Martinec A, Debono S, Finetti P, Carbuccia N, Beillard E, Devilard E, Arnoulet C, Coso D, Sainty D, Xerri L, Stoppa AM, Lafage-Pochitaloff M, Nguyen C, Houlgatte R, Blaise D, Maraninchi D, Birg F, Birnbaum D, Bertucci F
Conventional cytogenetic analysis currently stratifies acute myelogenous leukaemia (AML) into prognostically relevant groups. However, approximately 50% of adult AMLs have normal cytogenetics (NC-AMLs), and represent a heterogeneous and poorly understood group. We analysed gene expression in 55 AML samples including 53 cases from adult patients with NC-AML (n=36), trisomy 8, t(15;17), t(8;21), t(11;19), 7q deletion, and two cell lines using 9000-gene DNA microarrays. Global hierarchical clustering showed that NC-AMLs are a heterogeneous group. Supervised analysis distinguished two subgroups of NC-AML: one subgroup constituted a homogeneous NC cluster (‘pure NC-AML’), and the other NC-AMLs were close to the AML cases with translocations (‘translocation like’). Gene expression signatures were also derived for patients with trisomy 8, as well as FLT3 and MLL gene duplications. Importantly, samples from 24 NC-AML patients who could be evaluated for clinical outcome were analysed. In all, 43 genes that discriminated two classes of patients with significantly different prognosis were identified. The poor prognosis class contained a majority of ‘pure NC-AMLs’, whereas the ‘translocation-like’ AMLs were in the good prognosis class. Discriminator genes included genes involved in drug resistance (TOP2B), protein transport (MTX2, SLC35A2), and cell signalling (MAPK1, PRKAB2). Our results demonstrate the transcriptional heterogeneity of NC-AMLs, and suggest the existence of ‘translocation-like’ NC-AMLs and of a gene expression signature that may predict response to chemotherapy.Oncogene advance online publication, 15 November 2004; doi:10.1038/sj.onc.1207910.
http://www.hubmed.org/display.cgi?issn=09509232;uids=15543237
Posted by rob on under Uncategorized |
Mol Cell Biol. 2004 Dec; 24(23): 10289-99
Deming PB, Schafer ZT, Tashker JS, Potts MB, Deshmukh M, Kornbluth S
Bcr-Abl, activated in chronic myelogenous leukemias, is a potent cell death inhibitor. Previous reports have shown that Bcr-Abl prevents apoptosis through inhibition of mitochondrial cytochrome c release. We report here that Bcr-Abl also inhibits caspase activation after the release of cytochrome c. Bcr-Abl inhibited caspase activation by cytochrome c added to cell-free lysates and prevented apoptosis when cytochrome c was microinjected into intact cells. Bcr-Abl acted posttranslationally to prevent the cytochrome c-induced binding of Apaf-1 to procaspase 9. Although Bcr-Abl prevented interaction of endogenous Apaf-1 with the recombinant prodomain of caspase 9, it did not affect the association of endogenous caspase 9 with the isolated Apaf-1 caspase recruitment domain (CARD) or Apaf-1 lacking WD-40 repeats. These data suggest that Apaf-1 recruitment of caspase 9 is faulty in the presence of Bcr-Abl and that cytochrome c/dATP-induced exposure of the Apaf-1 CARD is likely defective. These data provide a novel locus of Bcr-Abl antiapoptotic action and suggest a distinct mechanism of apoptosomal inhibition.
http://www.hubmed.org/display.cgi?issn=02707306;uids=15542838
Posted by rob on under Uncategorized |
J Clin Oncol. 2004 Nov 15; 22(22): 4653-5
Breccia M, Muscaritoli M, Aversa Z, Mandelli F, Alimena G
http://www.hubmed.org/display.cgi?issn=0732183X;uids=15542819
Posted by rob on November 18, 2004 under Uncategorized |
Some girls and a boy walk through in a field of cosmos at a park in Saito, Miyazaki prefecture.
Posted by rob on November 17, 2004 under Uncategorized |
Bangladeshi children and women wearing traditional costumes carry paper flowers and play musical instruments as they take part a colourful march to celebrate the Eid-al Fitr Festival in Dhaka.
Posted by rob on November 16, 2004 under Uncategorized |
Tourists admire the view of the basilica of Sacre Coeur in Paris.
Posted by rob on November 15, 2004 under Uncategorized |
CMLHope.Com
A Global Community For CML
Our new CML web site is now open. It will provide a central location where you can access all of the resources that we have provided since 1997 which include online support groups, web forums, and local monthly support group meetings in over 60 countries. Our new CML Store provides a wide variety of merchandise with CMLHope and Meetup logos.
Volunteers Needed
Our new global network of local CML support groups needs local volunteers to be CML group organizers in communities in over 60 countries. You can apply online to be an organizer on the web site. If you need assistance contact
rob@cmlhope.com
Posted by rob on under Uncategorized |
An Indonesian Muslim woman raises her hands during prayers in celebration of the eve of Eid al-Fitr in Jakarta.
Posted by rob on under Uncategorized |
Treatment of chronic myeloid leukemia (CML) with imatinib (Gleevec(R)) induces a much higher rate of partial and complete cytogenetic responses (CCR) than interferon-alpha (IFN)-based therapies. Conventional wisdom suggests that elimination of the Philadelphia (Ph)- positive cells will lead to re-establishment of normal Ph-negative hematopoiesis. Surprisingly, karyotypic abnormalities were detected in the chromosome negative cells of some patients with cytogenetic response to imatinib. In some cases, this was associated with a myelodysplastic syndrome (MDS). While clonal evolution in Ph-positive cells is considered part of the progression of CML, clonal evolution in Ph-negative cells had been observed only rarely in a small number of patients treated with IFN or bone marrow transplantation, raising the question whether the phenomenon may be causally linked to imatinib therapy. In this manuscript, we will review the currently available data, suggest possible causes and discuss potential implications for patient management. We are fully aware that a systematic study of a larger patient cohort will be required to conclusively address these issues.
http://www.hubmed.org/display.cgi?issn=10428194;uids=15512807
Posted by rob on under Uncategorized |
Atwell S,
Adams JM,
Badger J,
Buchanan MD,
Feil IK,
Froning KJ,
Gao X,
Hendle J,
Keegan K,
Leon BC,
Müller-Dieckmann HJ,
Nienaber VL,
Noland BW,
Post K,
Rajashankar KR,
Ramos A,
Russell M,
Burley SK,
Buchanan SG
Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase required for signaling from immunoreceptors in various hematopoietic cells. Phosphorylation of two tyrosine residues in the activation loop of the Syk kinase catalytic domain is necessary for signaling, a phenomenon typical of tyrosine kinase family members. Syk in vitro enzyme activity, however, does not depend on phosphorylation (activation loop tyrosine to phenylalanine mutants retain catalytic activity). We have determined the X-ray structure of the unphosphorylated form of the kinase catalytic domain of Syk. The enzyme adopts a conformation of the activation loop typically seen only in activated, phosphorylated tyrosine kinases, explaining why Syk does not require phosphorylation for activation. We also demonstrate that Gleevec (STI-571, Imatinib) inhibits the isolated kinase domains of both unphosphorylated Syk and phosphorylated Abl with comparable potency. Gleevec binds Syk in a novel, compact cis conformation that differs dramatically from the binding mode observed with unphosphorylated Abl, the more Gleevec-sensitive form of Abl. This finding suggests the existence of two distinct Gleevec binding modes: an extended, trans conformation characteristic of tight binding to the inactive conformation of a protein kinase and a second compact, cis conformation characteristic of weaker binding to the active conformation, characteristic of activated protein kinases. Finally, the Syk-bound cis conformation of Gleevec bears a striking resemblance to rigid structure of the non-specific, natural product kinase inhibitor Staurosporine.
http://www.hubmed.org/display.cgi?issn=00219258;uids=15507431
Posted by rob on under Uncategorized |
Leukemia. 2004 10 21;
Weisberg E, Catley L, Kujawa J, Atadja P, Remiszewski S, Fuerst P, Cavazza C, Anderson K, Griffin JD
NVP-LAQ824 is a novel potent hydroxamic acid-derived histone deacetylase inhibitor that induces apoptosis in nanomolar concentrations in myeloid leukemia cell lines and patient samples. Here we show the activity of NVP-LAQ824 in acute myeloid leukemia cells and BCR/ABL-expressing cells of mouse and human origin, both sensitive and resistant to imatinib mesylate (Gleevec, STI-571). Whereas imatinib inhibited overall cellular tyrosine phosphorylation in Ba/F3.p210 cells, NVP-LAQ824 did not inhibit tyrosine phosphorylation, and did not affect BCR/ABL or ABL protein expression. Neither compound was able to inhibit cellular tyrosine phosphorylation in the imatinib-resistant Ba/F3.p210-T315I cell line. These data taken together suggest that BCR/ABL kinase activity is not a direct target of NVP-LAQ824. Synergy between NVP-LAQ824 and imatinib was demonstrated against BCR/ABL-expressing K562 myeloid leukemia cell lines. In addition, we show that NVP-LAQ824 was well tolerated in vivo in a pre-clinical murine leukemia model, with antileukemia activity resulting in significant prolongation of the survival of mice when treated with NVP-LAQ824 compared to control mice. Taken together, these findings provide the framework for NVP-LAQ824 as a novel therapeutic in myeloid malignancies.Leukemia advance online publication, 21 October 2004; doi:10.1038/sj.leu.2403519.
http://www.hubmed.org/display.cgi?issn=08876924;uids=15496979
Posted by rob on under Uncategorized |
BCR-ABL oncoprotein expressing cells are associated with a relative increase of intracellular reactive oxygen species (ROS), which is thought to play a role in transformation. Elevated ROS levels in BCR-ABL-transformed cells were found to be blocked by the mitochondrial complex I inhibitor rotenone as well as the glucose transport inhibitor phloretin, suggesting that the source of increased ROS might be related to increased glucose metabolism. The glucose analog 2-deoxyglucose (2-DOG) reduced ROS to levels found in non-BCR-ABL-transformed cells and inhibited cell growth alone or in cooperation with imatinib mesylate (Gleevec). A mutant of BCR-ABL that is defective in transformation of myeloid cells, Tyr177Phe, was also found to be defective in raising intracellular ROS levels. Glucose metabolism in BCR-ABL-transformed cells is likely to be mediated by activation of the phosphatidylinositol-3′-kinase (PI3K) pathway, which is regulated through this site. Inhibition of PI3K or mTOR led to a significant decrease in ROS levels. Overall, our results suggest that elevated levels of ROS in BCR-ABL-transformed cells are secondary to a transformation-associated increase in glucose metabolism and an over-active mitochondrial electron transport chain and is specifically regulated by PI3K. Finally, these results hint at novel targets for drug development that may aid traditional therapy.
http://www.hubmed.org/display.cgi?issn=00064971;uids=15486067
