当前位置： SCI文献检索 > BRITISH JOURNAL OF HAEMATOLOGY期刊下所有文献 > Inhibition of Akt induces significant downregulation of survivin and cytotoxicity in human multiple myeloma cells.

Inhibition of Akt induces significant downregulation of survivin and cytotoxicity in human multiple myeloma cells.

Abstract：

:Akt mediates growth and drug resistance in multiple myeloma (MM) cells in the bone marrow (BM) microenvironment. We have shown that a novel Akt inhibitor Perifosine induces significant cytotoxicity in MM cells in the BM milieu. This study further delineated molecular mechanisms whereby Perifosine triggered cytotoxicity in MM cells. Neither the intensity of Jun NH(2)-terminal kinase phosphorylation nor caspase/poly (ADP-ribose) polymerase cleavage correlated with Perifosine-induced cytotoxicity in MM.1S, INA6, OPM1 and OPM2 MM cells. However, survivin, which regulates caspase-3 activity, was markedly downregulated by Perifosine treatment, without changes in other anti-apoptotic proteins. Downregulation of survivin by siRNA significantly inhibited OPM1 MM cell growth, confirming that survivin mediates MM cell survival. Perifosine significantly downregulated both function and protein expression of beta-catenin. Co-culture with BM stromal cells (BMSCs) upregulated both beta-catenin and survivin expression in MM cells, which was blocked by Perifosine. Importantly, Perifosine treatment also downregulated survivin expression in human MM cells grown in vivo in a severe combined immunodeficient mouse xenograft model. Finally, Perifosine inhibited bortezomib-induced upregulation of survivin, associated with enhanced cytotoxicity of combined bortezomib and Perifosine treatment. These preclinical studies provide the framework for clinical trials of bortezomib with Perifosine to improve patient outcome in MM.

journal_name

Br J Haematol

journal_title

British journal of haematology

authors

Hideshima T,Catley L,Raje N,Chauhan D,Podar K,Mitsiades C,Tai YT,Vallet S,Kiziltepe T,Ocio E,Ikeda H,Okawa Y,Hideshima H,Munshi NC,Yasui H,Richardson PG,Anderson KC

doi

10.1111/j.1365-2141.2007.06714.x

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

783-91

issue

6

eissn

0007-1048

issn

1365-2141

pii

BJH6714

journal_volume

138

pub_type

杂志文章

相关文献

BRITISH JOURNAL OF HAEMATOLOGY文献大全
  • Responsiveness of bone marrow erythroid progenitors (CFU-E and BFU-E) to recombinant human erythropoietin (rh-Ep) in vitro in multiple myeloma.

    abstract：:The responsiveness of bone marrow erythroid progenitors (CFU-E and BFU-E) to recombinant human erythropoietin (rh-Ep) was investigated in vitro in 21 patients with multiple myeloma to assess the clinical usefulness of rh-Ep in this disease. CFU-E and BFU-E assays were performed by methylcellulose culture methods. The ...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1992.tb02976.x

    authors： Aoki I,Nishijima K,Homori M,Nakahara K,Higashi K,Ishikawa K

    更新日期：1992-08-01 00:00:00

  • Heterogenous band 3 deficiency in hereditary spherocytosis related to different band 3 gene defects.

    abstract：:Among 80 hereditary spherocytosis (HS) kindreds studied using denaturing electrophoretic separation of solubilized eythrocyte membrane proteins, we recognized three prominent subsets: HS with isolated spectrin deficiency, HS with combined spectrin and ankyrin deficiency, and HS with band 3 deficiency These three subse...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.1997.1893005.x

    authors： Dhermy D,Galand C,Bournier O,Boulanger L,Cynober T,Schismanoff PO,Bursaux E,Tchernia G,Boivin P,Garbarz M

    更新日期：1997-07-01 00:00:00

  • Delayed haemolytic transfusion reaction due to anti-M antibody.

    abstract：:A female patient with delayed haemolytic transfusion reaction due to anti-M antibody is described. Diagnosis was based on laboratory evidence of haemolysis and on characteristic serological findings. Anti-M was detected in the recipient's serum 7 d after the last transfusion episode. This alloantibody had not been pre...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.1998.00970.x

    authors： Sancho JM,Pujol M,Fernández F,Soler M,Manzano P,Feliu E

    更新日期：1998-10-01 00:00:00

  • Emerging pathogens and their implications for the blood supply and transfusion transmitted infections.

    abstract：:The threat of infection by conventional transfusion-transmitted agents has been essentially eliminated from the blood supply in developed countries, thus focusing attention on the potential risk from emerging infections. Over recent years, actions have been taken to manage a number of such risks to blood safety. These...

    journal_title：British journal of haematology

    pub_type： 杂志文章,评审

    doi：10.1111/bjh.12031

    authors： Dodd RY

    更新日期：2012-10-01 00:00:00

  • High frequencies of chromosomal aberrations in multiple myeloma and monoclonal gammopathy of undetermined significance in direct chromosome preparation.

    abstract：:Although many cases of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are cytogenetically normal, interphase fluorescence in situ hybridization (FISH) analyses reveal aberrations in the majority of the cases. Most likely, non-neoplastic cells are more prone to divide in culture tha...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.2004.05060.x

    authors： Nilsson T,Lenhoff S,Rylander L,Höglund M,Turesson I,Mitelman F,Westin J,Johansson B

    更新日期：2004-08-01 00:00:00

  • Isolation and culture of endothelial cells from human bone marrow.

    abstract：:Adhesive interactions between haemopoietic progenitor cells and bone marrow sinusoidal endothelium are potentially important in the homing of these cells back to the extravascular compartment of the marrow to re-establish haemopoiesis following stem cell transplantation. A simple method for the isolation and culture o...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1994.tb05128.x

    authors： Masek LC,Sweetenham JW

    更新日期：1994-12-01 00:00:00

  • Inter- and intra-patient clonal and subclonal heterogeneity of chronic lymphocytic leukaemia: evidences from circulating and lymph nodal compartments.

    abstract：:Whole exome sequencing and copy number aberration (CNA) analysis were performed on cells taken from peripheral blood (PB) and lymph nodes (LN) of patients with chronic lymphocytic leukaemia (CLL). Of 64 non-silent somatic mutations, 54 (84·4%) were clonal in both compartments, 3 (4·7%) were PB-specific and 7 (10·9%) w...

    journal_title：British journal of haematology

    pub_type： 杂志文章,多中心研究

    doi：10.1111/bjh.13859

    authors： Del Giudice I,Marinelli M,Wang J,Bonina S,Messina M,Chiaretti S,Ilari C,Cafforio L,Raponi S,Mauro FR,Di Maio V,De Propris MS,Nanni M,Ciardullo C,Rossi D,Gaidano G,Guarini A,Rabadan R,Foà R

    更新日期：2016-02-01 00:00:00

  • Successful excision of a pseudotumour in a congenitally factor V deficient patient.

    abstract：:We report a patient with congenital homozygous factor V deficiency in whom a large pseudotumour in the right upper leg was successfully surgically excised under continuous substitution with fresh-frozen plasma. ...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.1998.00570.x

    authors： Tanis BC,van der Meer FJ,Bloem RM,Vlasveld LT

    更新日期：1998-02-01 00:00:00

  • A phase II study of cyclophosphamide, etoposide, vincristine and prednisone (CEOP) Alternating with Pralatrexate (P) as front line therapy for patients with peripheral T-cell lymphoma (PTCL): final results from the T- cell consortium trial.

    abstract：:Peripheral T-cell lymphomas (PTCL) have suboptimal outcomes using conventional CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. The anti-folate pralatrexate, the first drug approved for patients with relapsed/refractory PTCL, provided a rationale to incorporate it into the front-line setting...

    journal_title：British journal of haematology

    pub_type： 杂志文章,多中心研究

    doi：10.1111/bjh.13855

    authors： Advani RH,Ansell SM,Lechowicz MJ,Beaven AW,Loberiza F,Carson KR,Evens AM,Foss F,Horwitz S,Pro B,Pinter-Brown LC,Smith SM,Shustov AR,Savage KJ,Vose JM

    更新日期：2016-02-01 00:00:00

  • Locus assignment of human alpha globin mutations by selective amplification and direct sequencing.

    abstract：:We describe a simple approach for molecular characterization and locus assignment of structural mutants by direct sequencing of enzymatically amplified DNA selective to alpha 1 and alpha 2 globin gene regions. Nucleotide substitution of two structural variants (Stanleyville II alpha 2(78Lys) and J Mexico alpha 2(54Glu...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1990.tb07884.x

    authors： Dodé C,Rochette J,Krishnamoorthy R

    更新日期：1990-10-01 00:00:00

  • alpha-Interferon in myelofibrosis: a case report.

    abstract：:A patient with advanced myeloid metaplasia was treated with alpha-interferon (29 months) with a remarkable response. He had anaemia, thrombocytopenia and hepatosplenomegaly with infarction. The initial bone marrow showed replacement with fibrosis with no evident haemopoietic cells. Post-therapy, the patient became asy...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1994.tb04802.x

    authors： Dalla KP,Zeigler ZR,Shadduck RK

    更新日期：1994-03-01 00:00:00

  • A three-base deletion removing a leucine residue in a leucine-rich repeat of platelet glycoprotein Ib alpha associated with a variant of Bernard-Soulier syndrome (Nancy I).

    abstract：:Leucine-rich repeats are conserved structural motifs present in the four components of the human platelet glycoprotein Ib/IX/V complex receptor for the adhesive protein von Willebrand factor. The absence or abnormality of this complex is responsible for Bernard-Soulier disease, an autosomal recessive bleeding disorder...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1995.tb03316.x

    authors： de la Salle C,Baas MJ,Lanza F,Schwartz A,Hanau D,Chevalier J,Gachet C,Briquel ME,Cazenave JP

    更新日期：1995-02-01 00:00:00

  • Thrombopoietin in Plasmodium falciparum malaria.

    abstract：:Thrombopoietin (TPO) is the key growth factor for platelet production and is elevated in states of platelet depletion. As thrombocytopenia is a common finding in malaria, we analysed TPO regulation before, during and after antimalarial treatment. Before treatment, TPO serum levels were significantly higher in patients...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.2000.02096.x

    authors： Kreil A,Wenisch C,Brittenham G,Looareesuwan S,Peck-Radosavljevic M

    更新日期：2000-06-01 00:00:00

  • Platelet peroxidase-positive blast cells in transient myeloproliferative disorder with Down's syndrome.

    abstract：:Transient myeloproliferative disorder accompanied by Down's syndrome has been characterized as exhibiting self-limiting haematological abnormalities. We studied six patients suffering from this disorder in order to clarify the biological nature of their blast cells. Metaphases of leucocytes stimulated with phytohaemag...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1988.tb06187.x

    authors： Suda J,Eguchi M,Ozawa T,Furukawa T,Hayashi Y,Kojima S,Maeda H,Tadokoro K,Sato Y,Miura Y

    更新日期：1988-02-01 00:00:00

  • Successful collection of peripheral blood progenitor cells in patients with acute myeloid leukaemia following early consolidation therapy with granulocyte colony-stimulating factor-supported high-dose cytarabine and mitoxantrone.

    abstract：:We evaluated the feasibility of collecting peripheral blood progenitor cells (PBPC) in patients with acute myeloid leukaemia (AML) following two cycles of induction chemotherapy with idarubicin, cytarabine and etoposide (ICE), and one cycle of consolidation therapy with high-dose cytarabine and mitoxantrone (HAM). Thi...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.1997.3933207.x

    authors： Schlenk RF,Döhner H,Pförsich M,Benner A,Fischer K,Hartmann F,Fischer JT,Weber W,Gunzer U,Pralle H,Haas R

    更新日期：1997-11-01 00:00:00

  • Inactivation of the retinoblastoma gene in acute myelogenous leukaemia.

    abstract：:To investigate the role of retinoblastoma susceptibility (RB) gene inactivation in leukaemogenesis, we evaluated 36 bone marrow specimens of acute leukaemia for RB protein expression by immunoprecipitation and Western blot analysis. 15 patients had no detectable RB protein at initial screening. However, nine of them w...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1992.tb06459.x

    authors： Tang JL,Yeh SH,Chen PJ,Lin MT,Tien HF,Chen YC

    更新日期：1992-11-01 00:00:00

  • Personal tales of venous thromboembolism in the UK the last 60 years: from no interest to clinical excellence.

    abstract：:Sixty years ago there was little interest in venous thromboembolism (VTE) in global medical circles, and the British were no different in this respect. And yet, from nowhere the clinical field has developed: now prevention and management of VTE accounts for a large part of many consultant haematologists' working life,...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/bjh.17152

    authors： Hunt BJ

    更新日期：2020-11-01 00:00:00

  • Symptomatic type 1 protein C deficiency caused by a de novo Ser270Leu mutation in the catalytic domain.

    abstract：:Heterozygosity for a C8524T transition in the protein C gene converting Ser270(TCG) to Leu(TTG) in the protease domain was identified in a family with venous thrombosis. The mutation was associated with parallel reduction in plasma levels of protein C anticoagulant activity and protein C antigen, which is consistent w...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.2001.02809.x

    authors： Lind B,Koefoed P,Thorsen S

    更新日期：2001-06-01 00:00:00

  • Development of a prognostic model for overall survival in multiple myeloma using the Connect® MM Patient Registry.

    abstract：:Median overall survival (OS) has improved for patients with newly diagnosed multiple myeloma (NDMM), but prognosis varies depending on baseline patient characteristics. Current models use data from selected clinical trial populations, which prevent application to patients in an unselected community setting that reflec...

    journal_title：British journal of haematology

    pub_type： 杂志文章,多中心研究

    doi：10.1111/bjh.16139

    authors： Terebelo HR,Abonour R,Gasparetto CJ,Toomey K,Durie BGM,Hardin JW,Jagannath S,Wagner L,Narang M,Flick ED,Srinivasan S,Yue L,Kitali A,Agarwal A,Rifkin RM,CONNECT MM Registry Investigators.

    更新日期：2019-12-01 00:00:00

  • Cycles of agglutination-disagglutination induced by ristocetin in thrombasthenic platelets.

    abstract：:An oscillatory pattern of platelet agglutination-disagglutination in response to Ristocetin (R) at narrow concentration ranges was observed in citrated platelet rich plasma (PRP) of 10 patients with Glanzmann's thrombasthenia. The cyclic pattern decreased in intensity over time, was reproducible, and was not pH depend...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1979.tb03726.x

    authors： Chediak J,Telfer MC,Vander Laan B,Maxey B,Cohen I

    更新日期：1979-09-01 00:00:00

  • High prevalence of low bone mass in thalassaemia major.

    abstract：:Cooley's original description of beta-thalassaemia major included marked bone deformities as a characteristic feature. These were thought to be due to expansion of haemopoiesis attempting to compensate for the congenital anaemia. Regular blood transfusions from infancy prevents these skeletal problems. Nevertheless, s...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.1998.01108.x

    authors： Jensen CE,Tuck SM,Agnew JE,Koneru S,Morris RW,Yardumian A,Prescott E,Hoffbrand AV,Wonke B

    更新日期：1998-12-01 00:00:00

  • Arginine therapy: a novel strategy to induce nitric oxide production in sickle cell disease.

    abstract：:To determine the effects of L-arginine (L-Arg) supplementation on nitric oxide metabolite (NOx) production, oral L-Arg was given to normal controls, sickle cell disease (SCD) patients at steady state and SCD patients hospitalized with a vaso-occlusive crisis (VOC). L-Arg (0.1 g/kg) increased NOx formation by 18.8 +/- ...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.2000.02403.x

    authors： Morris CR,Kuypers FA,Larkin S,Sweeters N,Simon J,Vichinsky EP,Styles LA

    更新日期：2000-11-01 00:00:00

  • A case of peroxidase-positive acute leukaemia expressing only T lineage lymphoid markers.

    abstract：:We report the clinical presentation and the morphological, immunophenotypic, cytogenetic and molecular genetic characteristics of a 14 1/2-year-old boy who had French-American-British (FAB) type M1 acute non-lymphocytic (ANLL) leukaemia with a common T-ALL immunological phenotype, with no myeloid associated antigen, e...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1994.tb03276.x

    authors： Lelong F,Chretien P,Jouault H,Bayani N,Bernaudin F,Lemerle S

    更新日期：1994-01-01 00:00:00

  • Marrow fibroblasts from patients with myeloproliferative disorders show increased sensitivity to human serum mitogens.

    abstract：:The growth of marrow fibroblasts from patients with myeloproliferative disorders (MPD) was investigated using platelet derived growth factor (PDGF) and human serum as mitogens in the presence of human plasma derived serum. The proliferation of fibroblasts in MPD patients was increased compared to normal individuals, e...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1988.tb07616.x

    authors： Kimura A,Katoh O,Kuramoto A

    更新日期：1988-06-01 00:00:00

  • Autologous bone marrow transplantation as consolidation therapy in the treatment of adult patients under 60 years with acute myeloid leukaemia in first complete remission: a prospective randomized Dutch-Belgian Haemato-Oncology Co-operative Group (HOVON)

    abstract：:The question as to whether autologous stem cell transplantation (SCT) after consolidation chemotherapy improves the probability of survival of patients with acute myeloid leukaemia (AML) in first remission has not been settled. Here, we present the results of a phase III study conducted in newly diagnosed adult AML pa...

    journal_title：British journal of haematology

    pub_type： 临床试验,杂志文章,随机对照试验

    doi：10.1111/j.1365-2141.2004.05282.x

    authors： Breems DA,Boogaerts MA,Dekker AW,Van Putten WL,Sonneveld P,Huijgens PC,Van der Lelie J,Vellenga E,Gratwohl A,Verhoef GE,Verdonck LF,Löwenberg B

    更新日期：2005-01-01 00:00:00

  • Analysis of 2013 European LeukaemiaNet (ELN) responses in chronic phase CML across four frontline TKI modalities and impact on clinical outcomes.

    abstract：:This study assessed the relevance of 2013 European LeukaemiaNet (ELN) response categories on patients treated with common frontline tyrosine kinase inhibitors (TKI) in chronic myeloid leukaemia in chronic phase (CML-CP). Four hundred and eighty-seven patients treated with imatinib (400 mg; IM 400, n = 70; 800 mg; IM80...

    journal_title：British journal of haematology

    pub_type： 临床试验,杂志文章,多中心研究

    doi：10.1111/bjh.13936

    authors： Jain P,Kantarjian H,Sasaki K,Jabbour E,Dasarathula J,Nogueras Gonzalez G,Verstovsek S,Borthakur G,Wierda W,Kadia T,Dellasala S,Pierce S,Ravandi F,O'Brien S,Cortes J

    更新日期：2016-04-01 00:00:00

  • Studies on the subcellular organelles of neutrophils in chronic granulocytic leukaemia with special reference to alkaline phosphatase.

    abstract：:The organelle pathology of neutrophils in chronic granulocytic leukaemia (CGL) was investigated by analytical subcellular fractionation. There were minor reductions in activity of some granule enzymes with an abnormal distribution in sucrose density gradients of the specific granules. There was a marked reduction of 5...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1979.tb05891.x

    authors： Rustin GJ,Peters TJ

    更新日期：1979-04-01 00:00:00

  • Neutrophil hypersegmentation in iron deficiency anaemia: a case-control study.

    abstract：:Neutrophil hypersegmentation (NH) is an important haematological feature of cobalamin or folate deficiency. As iron deficiency and folate deficiency often occur in the same target groups it is important to establish whether iron deficiency alone is a cause of NH. We report a case-control study which addresses this iss...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.1999.01756.x

    authors： Westerman DA,Evans D,Metz J

    更新日期：1999-12-01 00:00:00

  • Characterization of murine monoclonal antibodies directed against the Kell blood group glycoprotein.

    abstract：:Murine monoclonal antibodies (MoAbs) were produced against the blood group KEL1 glycoprotein (93 kD component) immunopurified from human erythrocytes. One monoclonal antibody, 5A11 (IgGa, kappa), detects by immunoblotting a 93 and 184 kD component from KEL: 1,-2 or KEL: -1,2 red cell membrane preparations, separated b...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1991.tb04539.x

    authors： Jaber A,Loirat MJ,Willem C,Bloy C,Cartron JP,Blanchard D

    更新日期：1991-10-01 00:00:00

  • Patient self-management of anticoagulation therapy: a trial-based cost-effectiveness analysis.

    abstract：:Demand for anticoagulation management is increasing due to an expansion of clinical indications for therapy. One possible model of care to meet demand is patient self-management (PSM), beneficial to patients who need control over their condition. This study aimed to determine the cost and cost-effectiveness of PSM of ...

    journal_title：British journal of haematology

    pub_type： 杂志文章,随机对照试验

    doi：10.1111/j.1365-2141.2006.06243.x

    authors： Jowett S,Bryan S,Murray E,McCahon D,Raftery J,Hobbs FD,Fitzmaurice D

    更新日期：2006-09-01 00:00:00