text:
Aliases: HE5, CDW52, EDDM5
Location: 1p36.11
Summary: -
Protein: CAMPATH-1 antigen
- elevation of cytosolic calcium ion concentration
- respiratory burst
CD52 Antigen
Receptors, IgG
B-Lymphocytes
Proto-Oncogene Proteins c-kit
Antibodies, Neoplasm
Xenograft Models
Antibodies, Monoclonal, Humanized
Sezary Syndrome
Leukemia, Prolymphocytic, T-Cell
Receptors, IgE
Leukemia, Prolymphocytic
Lymphoma, T-Cell, Peripheral
Chromosome Deletion
drug, Alemtuzumab (Mabcampath)
Chronic Lymphocytic Leukemia CD52 and Chronic Lymphocytic Leukemia View Publications 16
Leukaemia CD52 and T-Cell Leukemia View Publications 10
Li L, Peng M, Xue W, et al.
Integrated analysis of dysregulated long non-coding RNAs/microRNAs/mRNAs in metastasis of lung adenocarcinoma.
J Transl Med. 2018; 16(1):372 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Lung adenocarcinoma (LUAD), largely remains a primary cause of cancer-related death worldwide. The molecular mechanisms in LUAD metastasis have not been completely uncovered.
METHODS: In this study, we identified differentially expressed genes (DEGs), miRNAs (DEMs) and lncRNAs (DELs) underlying metastasis of LUAD from The Cancer Genome Atlas database. Intersection mRNAs were used to perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and co-expression network analysis. In addition, survival analyses of intersection mRNAs were conducted. Finally, intersection mRNAs, miRNAs and lncRNAs were subjected to construct miRNA-mRNA-lncRNA network.
RESULTS: A total of 1015 DEGs, 54 DEMs and 22 DELs were identified in LUAD metastasis and non-metastasis samples. GO and KEGG pathway analysis had proven that the functions of intersection mRNAs were closely related with many important processes in cancer pathogenesis. Among the co-expression interactions network, 22 genes in the co-expression network were over the degree 20. These genes imply that they have connections with many other gene nodes. In addition, 14 target genes (ARHGAP11A, ASPM, HELLS, PRC1, TMPO, ARHGAP30, CD52, IL16, IRF8, P2RY13, PRKCB, PTPRC, SASH3 and TRAF3IP3) were found to be associated with survival in patients with LUAD significantly (log-rank P < 0.05). Two lncRNAs (LOC96610 and ADAM6) acting as ceRNAs were identified based on the miRNA-mRNA-lncRNA network.
CONCLUSIONS: Taken together, the results may provide a novel perspective to develop a multiple gene diagnostic tool for LUAD prognosis, which might also provide potential biomarkers or therapeutic targets for LUAD.
Related: MicroRNAs
Blatt K, Menzl I, Eisenwort G, et al.
Phenotyping and Target Expression Profiling of CD34
Neoplasia. 2018; 20(6):632-642 [PubMed] Free Access to Full Article Related Publications
Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34
Related: Chronic Myeloid Leukemia (CML) CML - Molecular Biology Acute Myeloid Leukemia (AML)
Remon J, Abedallaa N, Taranchon-Clermont E, et al.
CD52, CD22, CD26, EG5 and IGF-1R expression in thymic malignancies.
Lung Cancer. 2017; 108:168-172 [PubMed] Related Publications
BACKGROUND: Thymic epithelial tumours are rare cancers for which new treatment options are required. Identification of putative predictive markers is important for developing clinical trials. We studied the expression of five putative predictive biomarkers, potentially actionable by approved experimental drugs.
METHODS: CD52, CD22, CD26, EG5, and IGF-1R expression were investigated by immunohistochemistry in formalin-fixed surgical samples of thymic epithelial tumour patients. All samples containing 10% positive epithelial tumour cells, independent of tumour cell intensity, were considered as positive. Correlation with histological subtype was performed.
RESULTS: 106 surgical samples (89 thymomas, 12 thymic carcinoma, and 5 thymic neuroendocrine tumours) were evaluated. Overall, CD52, CD22, CD26, EG5 and IGF-1R expression was observed in 7%, 42%, 25%, 42% and 77% of samples, respectively. CD52 expression was more frequent in B2 and B3 thymoma. All TET subtypes stained for CD22, mainly AB thymoma (68%). CD26 expression also correlated with AB thymoma (68%), and A thymoma (50%) subtype, while IGFR1 was the most common marker expressed by thymic carcinoma samples (92%), followed by EG5 (60%). Only EG5 expression was significantly higher in thymic carcinomas than in thymomas (75% vs. 38%, p=0.026).
CONCLUSIONS: Our data were consistent with a previous study of IGF-1R expression. Based on their expression, activity of agents targeting CD52, CD 22, CD26 and EG5 could be further explored in TET patients.
Related: CD22
Hu Z, Li S, Medeiros LJ, Sun T
TCL-1-positive hematogones in a patient with T-cell prolymphocytic leukemia after therapy.
Hum Pathol. 2017; 65:175-179 [PubMed] Related Publications
T-prolymphocytic leukemia (T-PLL) is a rare mature T-cell neoplasm characterized by proliferation of prolymphocytes. Most cases involve the T-cell leukemia-1 (TCL1) gene at 14q11.2 resulting in overexpression of TCL-1, which is helpful for distinguishing T-PLL from other T-cell neoplasms. We report a patient with T-PLL whose leukemic cells were positive for TCL-1 by immunohistochemistry but with a normal karyotype. The patient had anti-CD52 antibody therapy for 12 weeks. In a follow-up bone marrow biopsy specimen, numerous TCL-1-positive cells were present, which raised the differential diagnosis of residual T-PLL. However, further immunophenotypic studies confirmed that these cells were hematogones. Therefore a diagnosis of recovering bone marrow was established. The patient underwent stem cell transplant and is now in complete remission. This case demonstrates that hematogones can express TCL-1, and this knowledge is very important for the differential diagnosis in the follow-up marrow of T-PLL patients.
Related: Alemtuzumab (Mabcampath) Stem Cell and Bone Marrow Transplants TCL1A
Qasim W, Zhan H, Samarasinghe S, et al.
Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells.
Sci Transl Med. 2017; 9(374) [PubMed] Related Publications
Autologous T cells engineered to express chimeric antigen receptor against the B cell antigen CD19 (CAR19) are achieving marked leukemic remissions in early-phase trials but can be difficult to manufacture, especially in infants or heavily treated patients. We generated universal CAR19 (UCART19) T cells by lentiviral transduction of non-human leukocyte antigen-matched donor cells and simultaneous transcription activator-like effector nuclease (TALEN)-mediated gene editing of T cell receptor α chain and CD52 gene loci. Two infants with relapsed refractory CD19
Related: Alemtuzumab (Mabcampath) Stem Cell and Bone Marrow Transplants
Poirot L, Philip B, Schiffer-Mannioui C, et al.
Multiplex Genome-Edited T-cell Manufacturing Platform for "Off-the-Shelf" Adoptive T-cell Immunotherapies.
Adoptive immunotherapy using autologous T cells endowed with chimeric antigen receptors (CAR) has emerged as a powerful means of treating cancer. However, a limitation of this approach is that autologous CAR T cells must be generated on a custom-made basis. Here we show that electroporation of transcription activator-like effector nuclease (TALEN) mRNA allows highly efficient multiplex gene editing in primary human T cells. We use this TALEN-mediated editing approach to develop a process for the large-scale manufacturing of T cells deficient in expression of both their αβ T-cell receptor (TCR) and CD52, a protein targeted by alemtuzumab, a chemotherapeutic agent. Functionally, T cells manufactured with this process do not mediate graft-versus-host reactions and are rendered resistant to destruction by alemtuzumab. These characteristics enable the administration of alemtuzumab concurrently or prior to engineered T cells, supporting their engraftment. Furthermore, endowing the TALEN-engineered cells with a CD19 CAR led to efficient destruction of CD19(+) tumor targets even in the presence of the chemotherapeutic agent. These results demonstrate the applicability of TALEN-mediated genome editing to a scalable process, which enables the manufacturing of third-party CAR T-cell immunotherapies against arbitrary targets. As such, CAR T-cell immunotherapies can therefore be used in an "off-the-shelf" manner akin to other biologic immunopharmaceuticals
Related: Alemtuzumab (Mabcampath) Monoclonal Antibodies
Hasanali ZS, Saroya BS, Stuart A, et al.
Epigenetic therapy overcomes treatment resistance in T cell prolymphocytic leukemia.
Sci Transl Med. 2015; 7(293):293ra102 [PubMed] Free Access to Full Article Related Publications
T cell prolymphocytic leukemia (T-PLL) is a rare, mature T cell neoplasm with distinct features and an aggressive clinical course. Early relapse and short overall survival are commonplace. Use of the monoclonal anti-CD52 antibody alemtuzumab has improved the rate of complete remission and duration of response to more than 50% and between 6 and 12 months, respectively. Despite this advance, without an allogeneic transplant, resistant relapse is inevitable. We report seven complete and one partial remission in eight patients receiving alemtuzumab and cladribine with or without a histone deacetylase inhibitor. These data show that administration of epigenetic agents can overcome alemtuzumab resistance. We also report epigenetically induced expression of the surface receptor protein CD30 in T-PLL. Subsequent treatment with the anti-CD30 antibody-drug conjugate brentuximab vedotin overcame organ-specific (skin) resistance to alemtuzumab. Our findings demonstrate activity of combination epigenetic and immunotherapy in the incurable illness T-PLL, particularly in the setting of previous alemtuzumab therapy.
Related: Alemtuzumab (Mabcampath)
Gonçalves A, Vale S, Nobre E, et al.
Thyroid nodule: first manifestation of chronic lymphocytic leukaemia.
Arch Endocrinol Metab. 2015; 59(2):190-4 [PubMed] Related Publications
The presence of chronic lymphocytic leukaemia (CLL) cells in the thyroid gland is most likely due to a secondary involvement by a systemic disease. The reported incidence of CLL involving the thyroid is extremely low, representing about 3-4% of all thyroid lymphoproliferative neoplasm. We report a rare case of CLL presenting initially in the thyroid gland. Systemic disease was detected as a result of thyroid investigation. An 85 years old woman, with multinodular goiter without adenophaties, was referred to our department, carrying a fine needle aspiration biopsy (FNAB) report of a private institution referring "lymphoid monomorphic proliferation" and suggesting a "Core-needle biopsy" for further investigation. She was euthyroid (TSH-0.5 uU/mL (0.4-4.0), thyroid antibodies negative, including TRab). The patient denied systemic symptoms and at physical examination there were no adenophaties or organomegalies. FNAB analysis was repeated. Although the patient denied constitutional symptoms and there were no relevant findings in physical examination, technetium 99m thyroid gamagraphy (GG) and blood count were additionally asked. FNAB analysis concluded lymphocytic tiroiditis, but thyroid GG revelled global hypocaptation and blood count showed 173.4 x 109 leukocyte/L with 94% lymphocyte. An ecoguided FNAB with flow cytometry identified thyroid infiltration by monotonous population of blasts with phenotype consistent with CLL/malignancy of mature B-cells. CLL/malignancy of mature B-cells was also detected in peripheral blood analysis, suggesting systemic disease with secondary thyroid involvement. The patient started chemotherapy with rituximab and chlorambucil with good response. Pos-treatment GG revelled "Increased levels of uptake in the middle third of the right lower lobe, with low uptake of the remaining parenchyma". In conclusion, good communication with the pathologist can improve diagnostic accuracy and dictate appropriate therapy. The use of techniques such as flow cytometry, immunoglobulin gene rearrangements, and immunohistochemistry has improved diagnostic accuracy and obviated more invasive procedures, such as core needle or open surgery biopsy. Apart from chemotherapy, immunochemotherapy with anti-CD20 and anti-CD52 monoclonal antibodies can be used in the treatment of CLL.
Nevet MJ, Zuckerman T, Sahar D, Bergman R
Transformation of Sézary syndrome into CD30+ anaplastic large T-cell lymphoma after alemtuzumab therapy with evidence of clonal unity.
Am J Dermatopathol. 2015; 37(1):73-7 [PubMed] Related Publications
Alemtuzumab is a humanized mouse antibody targeting the CD52 cell surface, which has been effective in patients with advanced stage mycosis fungoides (MF) including erythrodermic MF and Sézary syndrome. There are a few descriptions of large cell transformation after its administration. A young patient with an acute onset of Sézary syndrome treated initially unsuccessfully with fludarabine and cyclophosphamide and later on successfully with alemtuzumab has been described. Three weeks after the beginning of therapy, however, she developed transformed T-cell lymphoma indistinguishable from CD30 anaplastic large-cell lymphoma. After bone marrow transplantation, the transformed CD30 cutaneous T-cell lymphoma recurred as a transformed CD30 plaque MF. All 3 types of lesions showed the same T-cell receptor clonal gene rearrangement, which supports the notion that Sézary syndrome, CD30 anaplastic large-cell lymphoma, and MF are interrelated.
Related: Alemtuzumab (Mabcampath) Skin Cancer
Le Jeune C, Thomas X
Antibody-based therapies in B-cell lineage acute lymphoblastic leukaemia.
Eur J Haematol. 2015; 94(2):99-108 [PubMed] Related Publications
Targeted therapies represent a major breakthrough in the treatment of adult acute lymphoblastic leukaemia (ALL). Because lymphoblastic leukaemia cells express a variety of specific antigens, those ones can serve as targets for monoclonal antibodies (MoAbs). Anti-CD20 (rituximab), anti-CD19 (blinatumomab, SAR3419), anti-CD22 (epratuzumab, inotuzumab ozogamicin) and anti-CD52 (alemtuzumab) have therefore been developed. Possible strategies even include recruitment of CD3 cytotoxic T cells (blinatumomab) or adoptive T-cell therapy by gene transfer of CD19-chimeric antigen receptors (CD19-CARs). Recent data show that antibody-based therapy is a highly promising treatment approach. However, optimal treatment approach still needs to be defined.
Related: Monoclonal Antibodies
Salama ME, Du S, Efimova O, et al.
Neoplastic plasma cell aberrant antigen expression patterns and their association with genetic abnormalities.
Little is known about aberrant antigen expression patterns and their association with cytogenetic aberrations in multiple myeloma (MM). We examined the correlation between flow cytometry and florescence in situ hybridization (FISH) in 167 marrow specimens with MM. Gene expression profiling of CD56, CD117, CD52 and CD20 mRNA in plasma cells (PCs) from patients treated on Total Therapy 2 and Total Therapy 3 trials were also evaluated. Higher expression of CD56 and CD117 was associated with hyperdiploidy. High CD52 mRNA expression was associated with c-MAF and FGFR3 subgroups. Higher expression of CD56 mRNA, but lower Kit expression, were noted in association with FGFR3. In contrast, the c-MAF subgroup showed high Kit expression but lacked NCAM mRNA expression. CKS1B amplification showed positive correlation with CD52 (p=0.0065) but negative correlation with CD20 (p=0.0207). These findings indicate that phenotypic differences in MM are associated with distinct genetic subgroups, which potentially has important diagnostic and prognostic value.
Related: FISH Myeloma Myeloma - Molecular Biology
Blatt K, Herrmann H, Hoermann G, et al.
Identification of campath-1 (CD52) as novel drug target in neoplastic stem cells in 5q-patients with MDS and AML.
Clin Cancer Res. 2014; 20(13):3589-602 [PubMed] Related Publications
PURPOSE: The CD52-targeted antibody alemtuzumab induces major clinical responses in a group of patients with myelodysplastic syndromes (MDS). The mechanism underlying this drug effect remains unknown.
EXPERIMENTAL DESIGN: We asked whether neoplastic stem cells (NSC) in patients with MDS (n = 29) or acute myelogenous leukemia (AML; n = 62) express CD52.
RESULTS: As assessed by flow cytometry, CD52 was found to be expressed on NSC-enriched CD34(+)/CD38(-) cells in 8/11 patients with MDS and isolated del(5q). In most other patients with MDS, CD52 was weakly expressed or not detectable on NSC. In AML, CD34(+)/CD38(-) cells displayed CD52 in 23/62 patients, including four with complex karyotype and del(5q) and one with del(5q) and t(1;17;X). In quantitative PCR (qPCR) analyses, purified NSC obtained from del(5q) patients expressed CD52 mRNA. We were also able to show that CD52 mRNA levels correlate with EVI1 expression and that NRAS induces the expression of CD52 in AML cells. The CD52-targeting drug alemtuzumab, was found to induce complement-dependent lysis of CD34(+)/CD38(-)/CD52(+) NSC, but did not induce lysis in CD52(-) NSC. Alemtuzumab also suppressed engraftment of CD52(+) NSC in NSG mice. Finally, CD52 expression on NSC was found to correlate with a poor survival in patients with MDS and AML.
CONCLUSIONS: The cell surface target Campath-1 (CD52) is expressed on NSC in a group of patients with MDS and AML. CD52 is a novel prognostic NSC marker and a potential NSC target in a subset of patients with MDS and AML, which may have clinical implications and may explain clinical effects produced by alemtuzumab in these patients.
Related: Alemtuzumab (Mabcampath) Chromosome 5 Acute Myeloid Leukemia (AML)
Hoermann G, Blatt K, Greiner G, et al.
CD52 is a molecular target in advanced systemic mastocytosis.
FASEB J. 2014; 28(8):3540-51 [PubMed] Related Publications
Advanced systemic mastocytosis (SM) is an aggressive hematopoietic neoplasm with poor prognosis and short survival times. So far, no curative therapy is available for affected patients. We have identified the cell surface antigen CD52 (CAMPATH-1) as a molecular target expressed abundantly on the surface of primary neoplastic mast cells (MCs) in patients with advanced SM. In contrast, neoplastic MCs of patients with indolent SM and normal MCs expressed only low levels or did not express CD52. To study the mechanisms of CD52 expression and the value of this antigen as a potential therapeutic target, we generated a human MC cell line, designated MCPV-1, by lentiviral immortalization of cord blood-derived MC progenitor cells. Functional studies revealed that activated RAS profoundly promotes surface expression of CD52. The CD52-targeting antibody alemtuzumab induced cell death in CD52(+) primary neoplastic MCs obtained from patients with SM as well as in MCPV-1 cells. NSG mice xenotransplanted with MCPV-1 cells survived significantly longer after treatment with alemtuzumab (median survival: 31 d untreated vs. 46 d treated; P=0.0012). We conclude that CD52 is a novel marker and potential therapeutic target in neoplastic MCs in patients with advanced SM.
Related: Alemtuzumab (Mabcampath) KRAS NRAS
Geisler CH, van T' Veer MB, Jurlander J, et al.
Frontline low-dose alemtuzumab with fludarabine and cyclophosphamide prolongs progression-free survival in high-risk CLL.
Blood. 2014; 123(21):3255-62 [PubMed] Related Publications
The randomized Haemato Oncology Foundation for Adults in The Netherlands 68 phase 3 trial compared front-line chemotherapy with chemotherapy plus the CD52 monoclonal antibody alemtuzumab for high-risk chronic lymphocytic leukemia, defined as at least 1 of the following: unmutated immunoglobulin heavy chain genes, deletion 17p or 11q, or trisomy 12. Fit patients were randomized to receive either 6 28-day cycles of oral FC chemotherapy (days 1 through 3: fludarabine 40 mg/m(2) per day and cyclophosphamide 250 mg/m(2) per day: n = 139) or FC plus subcutaneous alemtuzumab 30 mg day 1 (FCA, n = 133). FCA prolonged the primary end point, progression-free survival (3-year progression-free survival 53 vs 37%, P = .01), but not the secondary end point, overall survival (OS). However, a post hoc analysis showed that FCA increased OS in patients younger than 65 years (3-year OS 85% vs 76%, P = .035). FCA also increased the overall response rate (88 vs 78%, P = .036), and the bone marrow minimal residual disease-negative complete remission rate (64% vs 43%, P = .016). Opportunistic infections were more frequent following FCA, but without an increase in treatment related mortality (FCA: 3.8%, FC: 4.3%). FCA improves progression-free survival in high-risk chronic lymphocytic leukemia. As anticipated, FCA is more immunosuppressive than FC, but with due vigilance, does not lead to a higher treatment-related mortality. This study was registered at www.trialregister.nl as trial no. NTR529.
Related: Alemtuzumab (Mabcampath) Cyclophosphamide Chronic Lymphocytic Leukemia (CLL) CLL - Molecular Biology Fludarabine
Huang PY, Best OG, Almazi JG, et al.
Cell surface phenotype profiles distinguish stable and progressive chronic lymphocytic leukemia.
Leuk Lymphoma. 2014; 55(9):2085-92 [PubMed] Related Publications
Chronic lymphocytic leukemia (CLL) is clinically heterogeneous. While some patients have indolent disease for many years, 20-30% will progress and ultimately die of their disease. CLL may be classified by the Rai or Binet staging system, mutational status of the immunoglobulin variable heavy-chain gene (IGVH), ZAP-70 overexpression, cytogenetic abnormalities (13q-, + 12, 11q-, 17p-) and expression of several cell surface antigens (CD38, CD49d) that correlate with risk of disease progression. However, none of these markers identify all cases of CLL at risk. In a recent review, we summarized those CD antigens known to correlate with the prognosis of CLL. The present study has identified surface profiles of CD antigens that distinguish clinically progressive CLL from slow-progressive and stable CLL. Using an extended DotScan(™) CLL antibody microarray (Version 3; 182 CD antibodies), and with refined analysis of purified CD19 + B-cells, the following 27 CD antigens were differentially abundant for progressive CLL: CD11a, CD11b, CD11c, CD18, CD19, CD20 (two epitopes), CD21, CD22, CD23, CD24, CD25, CD38, CD40, CD43, CD45, CD45RA, CD52, CD69, CD81, CD84, CD98, CD102, CD148, CD180, CD196 and CD270. The extensive surface profiles obtained provide disease signatures with an accuracy of 79.2%, a sensitivity of 83.9% and a specificity of 72.5% that could provide the basis for a rapid test to triage patients with CLL according to probability of clinical progression and potential earlier requirement for treatment.
Park J, Bae EK, Lee C, et al.
Establishment and characterization of bortezomib-resistant U266 cell line: constitutive activation of NF-κB-mediated cell signals and/or alterations of ubiquitylation-related genes reduce bortezomib-induced apoptosis.
BMB Rep. 2014; 47(5):274-9 [PubMed] Free Access to Full Article Related Publications
Bortezomib has been known as the most promising anti-cancer drug for multiple myeloma (MM). However, recent studies reported that not all MM patients respond to bortezomib. To overcome such a stumbling-block, studies are needed to clarify the mechanisms of bortezomib resistance. In this study, we established a bortezomib-resistant cell line (U266/velR), and explored its biological characteristics. The U266/velR showed reduced sensitivity to bortezomib, and also showed crossresistance to the chemically unrelated drug thalidomide. U266/velR cells had a higher proportion of CD138 negative subpopulation, known as stem-like feature, compared to parental U266 cells. U266/velR showed relatively less inhibitory effect of prosurvival NF-κB signaling by bortezomib. Further analysis of RNA microarray identified genes related to ubiquitination that were differentially regulated in U266/velR. Moreover, the expression level of CD52 in U266 cells was associated with bortezomib response. Our findings provide the basis for developing therapeutic strategies in bortezomib-resistant relapsed and refractory MM patients.
Related: Apoptosis Bortezomib Myeloma Myeloma - Molecular Biology Signal Transduction Thalidomide SDC1
Gorin NC, Isnard F, Garderet L, et al.
Administration of alemtuzumab and G-CSF to adults with relapsed or refractory acute lymphoblastic leukemia: results of a phase II study.
Eur J Haematol. 2013; 91(4):315-21 [PubMed] Related Publications
The outlook for adults with refractory and relapsed acute lymphocytic leukemia (ALL) is poor. CD52 is expressed in most patients with ALL. Alemtuzumab is an anti-CD52 humanized monoclonal antibody. This phase II study assessed the efficacy of alemtuzumab combined with granulocyte-colony stimulating factor (G-CSF) to boost antibody-dependent cell cytotoxicity mediated by neutrophils. Twelve patients with relapsed (n = 11) or refractory (n = 1) ALL, including four relapses postallogeneic stem cell transplantation, were treated and monitored between October 2006 and January 2011. Patients received 1 wk of alemtuzumab every other day at increasing doses of 3, 10, and 30 mg to test tolerance and 30 mg three times a week for 12-18 infusions. If in complete remission (CR), patients received maintenance therapy for 1 wk, every 2 months. G-CSF was administered at 5 μg/kg per day during alemtuzumab administration. The primary endpoint was disappearance of blast cells on a marrow aspirate. CD52 was expressed in all patients. Four patients reached CR. In one additional patient, clearance of blast cells was observed in peripheral blood but not in the marrow. The most frequent adverse events during course 1 of treatment were fever and chills (n = 3), skin rash (n = 3), and bronchospasm (n = 2). Tumor lysis syndrome was observed at treatment initiation in one patient who reached CR. All patients progressed within a few months and all but one died. The surviving patient is still alive after relapse and a second allogeneic stem cell transplantation. This study shows that in relapse/refractory ALL, alemtuzumab with G-CSF can produce good responses of short duration.
Related: Alemtuzumab (Mabcampath) Acute Lymphocytic Leukemia (ALL)
Bisig B, de Reyniès A, Bonnet C, et al.
CD30-positive peripheral T-cell lymphomas share molecular and phenotypic features.
Haematologica. 2013; 98(8):1250-8 [PubMed] Free Access to Full Article Related Publications
Peripheral T-cell lymphoma, not otherwise specified is a heterogeneous group of aggressive neoplasms with indistinct borders. By gene expression profiling we previously reported unsupervised clusters of peripheral T-cell lymphomas, not otherwise specified correlating with CD30 expression. In this work we extended the analysis of peripheral T-cell lymphoma molecular profiles to prototypical CD30(+) peripheral T-cell lymphomas (anaplastic large cell lymphomas), and validated mRNA expression profiles at the protein level. Existing transcriptomic datasets from peripheral T-cell lymphomas, not otherwise specified and anaplastic large cell lymphomas were reanalyzed. Twenty-one markers were selected for immunohistochemical validation on 80 peripheral T-cell lymphoma samples (not otherwise specified, CD30(+) and CD30(-); anaplastic large cell lymphomas, ALK(+) and ALK(-)), and differences between subgroups were assessed. Clinical follow-up was recorded. Compared to CD30(-) tumors, CD30(+) peripheral T-cell lymphomas, not otherwise specified were significantly enriched in ALK(-) anaplastic large cell lymphoma-related genes. By immunohistochemistry, CD30(+) peripheral T-cell lymphomas, not otherwise specified differed significantly from CD30(-) samples [down-regulated expression of T-cell receptor-associated proximal tyrosine kinases (Lck, Fyn, Itk) and of proteins involved in T-cell differentiation/activation (CD69, ICOS, CD52, NFATc2); upregulation of JunB and MUM1], while overlapping with anaplastic large cell lymphomas. CD30(-) peripheral T-cell lymphomas, not otherwise specified tended to have an inferior clinical outcome compared to the CD30(+) subgroups. In conclusion, we show molecular and phenotypic features common to CD30(+) peripheral T-cell lymphomas, and significant differences between CD30(-) and CD30(+) peripheral T-cell lymphomas, not otherwise specified, suggesting that CD30 expression might delineate two biologically distinct subgroups.
Chen J, Pise-Masison CA, Shih JH, et al.
Markedly additive antitumor activity with the combination of a selective survivin suppressant YM155 and alemtuzumab in adult T-cell leukemia.
Blood. 2013; 121(11):2029-37 [PubMed] Free Access to Full Article Related Publications
Adult T-cell leukemia (ATL) is an aggressive malignancy of CD4(+)CD25(+) lymphocytes caused by human T-cell lymphotropic virus type 1. Currently, there is no accepted curative therapy for ATL. In gene expression profiling, the antiapoptotic protein survivin (BIRC5) demonstrated a striking increase in ATL, and its expression was increased in patient ATL cells resistant to the anti-CD52 monoclonal antibody alemtuzumab (Campath-1H). In this study, we investigated the antitumor activity of a small-molecule survivin suppressant YM155 alone and in combination with alemtuzumab in a murine model of human ATL (MET-1). Both YM155 alone and its combination with alemtuzumab demonstrated therapeutic efficacy by lowering serum soluble IL-2Rα (sIL-2Rα) levels (P < .001) and prolonged the survival of tumor-bearing mice (P < .0001). Moreover, the combination of YM155 with alemtuzumab demonstrated markedly additive antitumor activity by significantly lowering serum sIL-2Rα levels and improving the survival of leukemia-bearing mice compared with monotherapy with either YM155 (P < .001) or alemtuzumab (P < .05). More significantly, all mice that received the combination therapy survived and were tumor free >6 months after treatment. Our data support a clinical trial of the combination of YM155 with alemtuzumab in ATL. This trial was registered at www.clinicaltrials.gov as #NCT00061048.
Related: Alemtuzumab (Mabcampath) BIRC5
Pettitt AR, Jackson R, Carruthers S, et al.
Alemtuzumab in combination with methylprednisolone is a highly effective induction regimen for patients with chronic lymphocytic leukemia and deletion of TP53: final results of the national cancer research institute CLL206 trial.
J Clin Oncol. 2012; 30(14):1647-55 [PubMed] Related Publications
PURPOSE: In chronic lymphocytic leukemia (CLL), TP53 deletion/mutation is strongly associated with an adverse outcome and resistance to chemotherapy-based treatment. In contrast, TP53 defects are not associated with resistance to the anti-CD52 monoclonal antibody alemtuzumab or methylprednisolone. In an attempt to improve the treatment of TP53-defective CLL, a multicenter phase II study was developed to evaluate alemtuzumab and methylprednisolone in combination.
PATIENTS AND METHODS: Thirty-nine patients with TP53-deleted CLL (17 untreated and 22 previously treated) received up to 16 weeks of treatment with alemtuzumab 30 mg three times a week and methylprednisolone 1.0 g/m(2) for five consecutive days every 4 weeks. Antimicrobial prophylaxis consisted of cotrimoxazole, itraconazole, and aciclovir (or valganciclovir for asymptomatic cytomegalovirus viremia). The primary end point was response as assigned by an end-point review committee. Secondary end points were safety, progression-free survival (PFS) and overall survival (OS).
RESULTS: The overall response rate, complete response rate (including with incomplete marrow recovery), median PFS, and median OS were 85%, 36%, 11.8 months, and 23.5 months, respectively, in the entire cohort and 88%, 65%, 18.3 months, and 38.9 months, respectively, in previously untreated patients. Grade 3 to 4 hematologic and glucocorticoid-associated toxicity occurred in 67% and 23% of patients, respectively. Grade 3 to 4 infection occurred in 51% of the overall cohort and in 29% of patients less than 60 years of age. Treatment-related mortality was 5%.
CONCLUSION: Alemtuzumab plus methypredisolone is the most effective induction regimen hitherto reported in TP53-deleted CLL. The risk of infection is age related and, in younger patients, seems only marginally higher than that associated with rituximab, fludarabine, and cyclophosphamide.
Related: Alemtuzumab (Mabcampath) Chronic Lymphocytic Leukemia (CLL) CLL - Molecular Biology
Leskov I, Pallasch CP, Drake A, et al.
Rapid generation of human B-cell lymphomas via combined expression of Myc and Bcl2 and their use as a preclinical model for biological therapies.
Oncogene. 2013; 32(8):1066-1072 [PubMed] Free Access to Full Article Related Publications
Although numerous mouse models of B-cell malignancy have been developed via the enforced expression of defined oncogenic lesions, the feasibility of generating lineage-defined human B-cell malignancies using mice reconstituted with modified human hematopoietic stem cells (HSCs) remains unclear. In fact, whether human cells can be transformed as readily as murine cells by simple oncogene combinations is a subject of considerable debate. Here, we describe the development of humanized mouse model of MYC/BCL2-driven 'double-hit' lymphoma. By engrafting human HSCs transduced with the oncogene combination into immunodeficient mice, we generate a fatal B malignancy with complete penetrance. This humanized-MYC/BCL2-model (hMB) accurately recapitulates the histopathological and clinical aspects of steroid-, chemotherapy- and rituximab-resistant human 'double-hit' lymphomas that involve the MYC and BCL2 loci. Notably, this model can serve as a platform for the evaluation of antibody-based therapeutics. As a proof of principle, we used this model to show that the anti-CD52 antibody alemtuzumab effectively eliminates lymphoma cells from the spleen, liver and peripheral blood, but not from the brain. The hMB humanized mouse model underscores the synergy of MYC and BCL2 in 'double-hit' lymphomas in human patients. Additionally, our findings highlight the utility of humanized mouse models in interrogating therapeutic approaches, particularly human-specific monoclonal antibodies.
Related: MYC
Matutes E
Novel and emerging drugs for rarer chronic lymphoid leukaemias.
Curr Cancer Drug Targets. 2012; 12(5):484-504 [PubMed] Related Publications
Rarer chronic lymphoid leukaemias represent a challenge to the clinicians due to the limited information on their pathogenesis, difficulties on setting up prospective clinical trials and to their refractoriness to drugs used in the most common form of chronic lymphocytic leukaemia (CLL). In this review all these issues are addressed in three B-cell leukaemias: B-cell prolymphocytic leukaemia (B-PLL), hairy cell leukaemia (HCL) and HCL-variant and three T-cell leukaemias: T-cell prolymphocytic leukaemia (T-PLL), T-cell large granular lymphocytic leukaemia (T-cell LGLL) and adult T-cell leukaemia lymphoma (ATLL). Data will be presented on the natural history, current therapies and emerging drugs potentially useful in the treatment of patients with these leukaemias. Emphasis is made on: 1- the novel agents targeting a variety of B and T-cell antigens expressed on the surface of the leukaemic cells; these are either unconjugated monoclonal antibodies (McAb) such as Rituximab (anti-CD20), the second and third generation of anti-CD20 McAbs, Alemtuzumab (anti-CD52), Siplizumab (anti-CD2), Daclizumab (anti-CD25) and KW-0761, an anti-chemokine receptor 4 (CCR4) or McAbs conjugated to toxins such as CD22 linked to the pseudomonas exotoxin or radiolabelled McAb; 2- the use of new purine nucleosides such as nelarabine and 3- agents targeting deregulated genes in the leukaemic cells from these diseases such as the Poly (ADP-ribose) polymerase (PARP) Olarapib in T-PLL with deregulation of the ataxia telangiectasia mutated (ATM) gene. Data of phase I and II clinical studies with these agents as well as the potential and current use of other drugs are outlined.
Bisig B, Gaulard P, de Leval L
New biomarkers in T-cell lymphomas.
Best Pract Res Clin Haematol. 2012; 25(1):13-28 [PubMed] Related Publications
Peripheral T-cell lymphomas (PTCLs) are heterogeneous and uncommon malignancies characterized by an aggressive clinical course and a mostly poor outcome with current treatment strategies. The recent genome-wide molecular characterization of several entities has provided novel insights into their pathobiology and led to the identification of new biomarkers with diagnostic, prognostic or therapeutic implications for PTCL patients. Cell lineage and differentiation antigens (markers of γδ or NK lineage, of cytotoxicity, of follicular helper T cells) reflect the tumour's biological behaviour, and their detection in tissue samples may refine the diagnostic and prognostic stratification of the patients. Previously unrecognized gene rearrangements are being discovered (ITK-SYK translocation, IRF4/MUM1 and DUSP22 rearrangements), and may serve as diagnostic genetic markers. Deregulated molecules within oncogenic pathways (NF-κB, Syk, PDGFRα) and immunoreactive cell-surface antigens (CD30, CD52) have been brought to the fore as potential targets for guiding the development of novel therapies.
Nguyen TH, Havari E, McLaren R, et al.
Alemtuzumab induction of intracellular signaling and apoptosis in malignant B lymphocytes.
Leuk Lymphoma. 2012; 53(4):699-709 [PubMed] Related Publications
The molecular changes induced by alemtuzumab following binding of CD52 on B tumor cells were investigated. Alemtuzumab alone had no detectable impact on cell signaling but cross-linking of alemtuzumab on the surface of B tumor lines with anti-human Fc antibodies induced a transient Ca(2+) flux followed by phosphorylation of several kinases involved in stress and survival pathways, and expression of associated proteins including TNF-α. Cross-linking of alemtuzumab also induced capping and caspase-dependent apoptosis of the tumor lines. When using primary cells from B-CLL patients, alemtuzumab alone was capable of inducing protein phosphorylation and apoptosis through the cross-linking of alemtuzumab by FcγRIIb receptors on B-CLL cells. Apoptosis was prevented by blocking of FcγRIIb receptors with anti-CD32 antibody. Overall, our results indicate that cross-linking of alemtuzumab on B tumor cells can occur naturally through Fc receptor interaction and leads to the activation of specific cellular pathways and induction of apoptosis.
Related: Alemtuzumab (Mabcampath) Apoptosis Chronic Lymphocytic Leukemia (CLL) CLL - Molecular Biology AKT1 Signal Transduction TNF
Saito Y, Nakahata S, Yamakawa N, et al.
CD52 as a molecular target for immunotherapy to treat acute myeloid leukemia with high EVI1 expression.
Leukemia. 2011; 25(6):921-31 [PubMed] Related Publications
Ecotropic viral integration site 1 (EVI1) is an oncogenic transcription factor in human acute myeloid leukemia (AML) with chromosomal alterations at 3q26. Because a high expression of EVI1 protein in AML cells predicts resistance to chemotherapy with a poor outcome, we have searched for molecular targets that will treat these patients with AML. In this study, we determined that CD52, which is mainly expressed on lymphocytes, is highly expressed in most cases of AML with a high EVI1 expression (EVI1(High)). CAMPATH-1H, a humanized monoclonal antibody against CD52, has been used to prevent graft-versus-host disease and treat CD52-positive lymphoproliferative disorders. Here, we investigated the antitumor effect of CAMPATH-1H on EVI1(High) AML cells. CAMPATH-1H significantly inhibited cell growth and induced apoptosis in CD52-positive EVI1(High) leukemia cells. Furthermore, CAMPATH-1H induced complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity against CD52-positive EVI1(High) leukemia cells. After an intravenous injection of CAMPATH-1H into NOD/Shi-scid/IL-2Rγ;null mice with subcutaneous engraftment of EVI1(High) leukemia cells, tumor growth rates were significantly reduced, and the mice survived longer than those in the phosphate-buffered saline-injected control group. Thus, CAMPATH-1H is a potential therapeutic antibody for the treatment of patients with EVI1(High) leukemia.
Related: Acute Myeloid Leukemia (AML) EVI1
Savage KJ, Ferreri AJ, Zinzani PL, Pileri SA
Peripheral T-cell lymphoma--not otherwise specified.
Crit Rev Oncol Hematol. 2011; 79(3):321-9 [PubMed] Related Publications
Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) does correspond to a heterogeneous group of nodal and extranodal mature T-cell lymphomas, with a low prevalence in Western countries. PTCL-NOS accounts for about 25% of all PTCL, which represent over 15% of all lymphomas. In the lymph node, PTCL-NOS shows paracortical or diffuse infiltrates with effacement of the normal architecture, with a broad cytological spectrum and a frequently observed inflammatory background. Some morphological variants include: lymphoepithelioid or Lennert's type, T-zone, and follicular. PTCL-NOS is characterized by an aberrant T-cell phenotype, with frequent loss of CD5 and CD7. A CD4+/CD8- phenotype predominates in nodal cases. CD4/CD8 +/+ or -/- is at times seen, as is CD8, CD56 and cytotoxic granule expression. Ki-67 rate is typically high. TCR β-chain is usually expressed; TCR genes are most often clonally rearranged. PTCL-NOS typically occurs in adults (median age 55-60 years), with a higher prevalence in males. It presents more often as disseminated disease, occasionally with eosinophilia, pruritis or hemophagocytic syndrome. Patients often have B symptoms, generalized lymphadenopathy, bone marrow infiltration, and extranodal involvement, with high or high-intermediate IPI score in 50-70% of cases. Prognosis is poor, with a 5-year OS of 20-30%. Some variables, like ST2(L), CXCR5, CXCR3, EBV infection, cytotoxic granule expression, high proliferative index, NF-κB expression, were proposed as prognostic indicators, but the IPI score, and its variant called PIT, remains the most effective prognostic factor. Patients with PTCL-NOS should be treated with anthracycline-containing chemotherapy, followed by radiotherapy in cases of stage I-II disease. This strategy is associated with an overall response rate higher than 60%, but the 5-year overall survival is only 20-30%. Upfront high-dose chemotherapy supported by autologous or allogeneic SCT is an investigational approach, with a 4-year overall survival of about 40%. Patients with chemosensitive relapse respond favorably to high-dose chemotherapy and ASCT, with long-term survival rates of 35-45%. Graft-versus-lymphoma effect following allogeneic SCT has been observed; and reduced intensity conditioning emerges as an attractive strategy for frail patients. Most patients with PTCL-NOS are enrolled in prospective trials to explore new approaches, and new agents, like gemcitabine, alemtuzumab and pralatrexate, are being investigated.
Querfeld C, Mehta N, Rosen ST, et al.
Alemtuzumab for relapsed and refractory erythrodermic cutaneous T-cell lymphoma: a single institution experience from the Robert H. Lurie Comprehensive Cancer Center.
Leuk Lymphoma. 2009; 50(12):1969-76 [PubMed] Related Publications
We present the results of an open-label clinical trial and the clinical use of alemtuzumab in 19 heavily pretreated patients with advanced erythrodermic cutaneous T-cell lymphomas (CTCL) (erythrodermic mycosis fungoides and Sézary syndrome). Ten patients received alemtuzumab intravenously using an escalating dose regimen with a final dose of 30 mg three times weekly for 4 weeks followed by subcutaneous administration for 8 weeks. Nine patients were treated with only the SQ or IV dosing. The overall response rate was 84%, with 9 (47%) complete and 7 (37%) partial remissions. The median follow-up was 24 months (range, 6 to 62+ months). Median overall survival was 41 months whereas median progression free survival was 6 months. Minimal residual disease by T-cell gene rearrangement studies was detected in 11 patients who achieved complete response and partial response. Toxicities included myelosuppression and infections; however, the majority of side effects were of Grade 2 in severity and transient. One patient was diagnosed with a concurrent lymphoma (mantle cell lymphoma) 6 months after completing alemtuzumab therapy. Alemtuzumab is particularly effective in patients with erythrodermic CTCL with acceptable toxicities. Combined strategies with alemtuzumab may achieve molecular remissions with longer response durations.
Related: Alemtuzumab (Mabcampath) Monoclonal Antibodies Skin Cancer
Mohan SR, Clemente MJ, Afable M, et al.
Therapeutic implications of variable expression of CD52 on clonal cytotoxic T cells in CD8+ large granular lymphocyte leukemia.
Haematologica. 2009; 94(10):1407-14 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: T-cell large granular lymphocytic leukemia is a clonal proliferation of cytotoxic T-lymphocytes which often results in severe cytopenia. Current treatment options favor chronic immunosuppression. Alemtuzumab, a humanized monoclonal antibody against glycophosphatidylinositol-anchored CD52, is approved for patients refractory to therapy in other lymphoid malignancies.
DESIGN AND METHODS: We retrospectively examined treatment outcomes in 59 patients with CD8+ T-cell large granular lymphocytic leukemia, 41 of whom required therapy. Eight patients with severe refractory cytopenia despite multiple treatment regimens had been treated with subcutaneous alemtuzumab as salvage therapy. Flow cytometry was used to monitor expression of glycophosphatidylinositol-anchored CD52, CD55, and CD59 as well as to characterize T-cell clonal expansions by T-cell receptor variable beta-chain (Vbeta) repertoire.
RESULTS: Analysis of the effects of alemtuzumab revealed remissions with restoration of platelets in one of one patient, red blood cell transfusion independence in three of five patients and improvement of neutropenia in one of three, resulting in an overall response rate of 50% (4/8 patients). Clonal large granular lymphocytes exhibited decreased CD52 expression post-therapy in patients refractory to treatment. Samples of large granular lymphocytes collected prior to therapy also unexpectedly had a significant proportion of CD52-negative cells while a healthy control population had no such CD52 deficiency (p=0.026).
CONCLUSIONS: While alemtuzumab may be highly effective in large granular lymphocytic leukemia, prospective serial monitoring for the presence of CD52-deficient clonal cytotoxic T-lymphocytes should be a component of clinical trials investigating the efficacy of this drug. CD52 deficiency may explain lack of response to alemtuzumab, and such therapy may confer a survival advantage to glycophosphatidylinositol-negative clonal cytotoxic T-lymphocytes.
Zwick C, Preuss KD, Kubuschok B, et al.
Analysis of the antibody repertoire of patients with mantle cell lymphoma directed against mantle cell lymphoma-associated antigens.
Ann Hematol. 2009; 88(10):999-1003 [PubMed] Related Publications
Treatment results of mantle cell lymphomas (MCL) are not satisfactory and novel therapeutic approaches are warranted. Because "shared" tumor antigens like the group of cancer testis antigens are only rarely expressed in MCL, we applied serological analysis of antigens using recombinant expression cloning (SEREX) to a complementary DNA library derived from five cases of MCL using the sera of eight patients with MCL in order to define MCL-associated antigens that are immunogenic in these patients and might be used as vaccines for patients with MCL. Five antigens were detected by SEREX. Four of the five detected antigens (hypothetical protein FLK10233, recombining binding protein suppressor, a chromosomal sequence, and interleukin-1 receptor associated kinase) are also expressed by a wide spectrum of normal human cells, excluding their use as vaccines. In contrast, the expression of CD52, which was detected by antibodies in the serum of an MCL patient, is restricted to hematopoietic cells. Interestingly, anti-CD52 antibodies were detected in this patient before and >2 years after allogeneic transplantation, indicating that both the autologous as well as the allogeneic immune system recognized CD52. Since the anti-CD52 monoclonal antibody alemtuzumab has shown activity in MCL, a vaccine consisting of recombinant CD52 alone or combined with passive immunotherapy using alemtuzumab warrants furthers clinical and immunological evaluation in MCL.
Related: Mantle Cell Lymphoma
Ahmed N, Leung KS, Rosenblatt H, et al.
Successful treatment of stem cell graft failure in pediatric patients using a submyeloablative regimen of campath-1H and fludarabine.
Biol Blood Marrow Transplant. 2008; 14(11):1298-304 [PubMed] Related Publications
Graft failure is a significant cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). We used a nonmyeloablative conditioning regimen consisting of the lympho-depleting humanized CD52-antibody Campath-1H and fludarabine to rescue 12 consecutive children age 9 months to 17 years with engraftment failure after initial myeloablative HSCT. Primary diagnoses included lymphohematologic malignancies (n=6), severe combined immunodeficiency syndrome (SCID) (n=4), and metabolic diseases (n=2). The same stem cell donor was used as for the primary graft: mismatched family member (n=7), matched unrelated donor (n=4), or matched related donor (n=1). The patients received doses of CD34+ cells that did not significantly differ from those used in the initial, failed transplant. At a median follow-up of 51 months (range, 4 to 84 months), 6 of 6 patients with nonmalignant diseases and 4 of 6 patients with malignancy were alive. Two patients died, 1 patient from pulmonary toxicity and 1 from relapse, at 51 days and 8 months posttransplantation, respectively. All 12 patients initially achieved sustained neutrophil engraftment and complete donor chimerism by day 28. Six patients received donor lymphocyte infusion (DLI) after "rescue" therapy to maintain donor chimerism. At 6 months, 4 patients had complete donor cell engraftment, 4 had 15% to 89% stable donor chimerism, and 3 had developed secondary graft failure. This conditioning regimen was generally well tolerated; 4 of the 12 patients never became neutropenic, and 9 never became thrombocytopenic. Only 1 patient developed graft-versus-host disease (GVHD; grade 1), and none had chronic GVHD. Thus, the regimen that we describe can be used with minimal toxicity to effectively overcome graft failure after myeloablative HSCT in children.
Related: Alemtuzumab (Mabcampath) Monoclonal Antibodies Haematological Malignancies & Realted Disorders Fludarabine


text:
Todos comunicados de prensa
Descubre enel.com
Electric mobility: Enel X, Nissan and RSE launch Italy's first test of Vehicle-to-Grid technology applied to innovative services
Published on viernes, 24 mayo 2019
A centre for testing V2G technology, equipped with Nissan LEAF cars and charging infrastructure developed by Enel X, has been established in collaboration with Nissan and Enel X at the RSE facilities in Milan
Through V2G, electric vehicles can exchange electricity with public and domestic grids with numerous benefits for the community, energy operators and customers
Milan, May 24th, 2019 - Enel X, Nissan and RSE have launched the first testing programme in Italy for the development and demonstration of vehicle-to-grid (V2G) technology, which enables electric vehicles (EV) to store and deliver electricity to help stabilise the electricity grid. The project involves the use of two Enel X bi-directional recharging systems, installed in the experimental RSE micro-grid, which, using a specific control platform, enables the use of Nissan LEAFs for grid stabilisation. The comprehensive range of functions that will be tested, which include a broad range of ancillary services, such as the optimisation of user electricity flows, makes this project a first in Europe as well.
Today, EVs are increasingly integrated into the energy ecosystem, moving from their traditional role as a means of transport to one in which they are energy vectors, playing an important part in the transition from fossil fuels to renewable resources.
The objective of the project is to test V2G functionalities based on the habits of private users and those who use corporate fleet vehicles. During recharging, the batteries will be used as energy storage systems connected to the grid, offering a range of advantages to the electricity system and car owners.
More specifically, V2G technology will make it possible to maximise the self-consumption of renewable energy generated by domestic systems, optimise the flows of power generated and consumed locally and ensure the continuity of electricity supply in the event of interruptions. An additional benefit for electric car owners is that they can earn money for the services provided to the electricity system, maximising the environmental and economic benefits of zero-emission mobility.
The possibility of using batteries for multiple purposes through V2G will give car owners a domestic or corporate power storage system at no extra cost and, in addition, will make an important contribution to the stability and efficiency of the electricity system: a tool that can further promote the take-up of electric vehicles in Italy.
The spread of non-schedulable renewable sources, especially solar and wind power, requires new flexibility systems, among which electricity storage technologies will play an essential role in this area. The expected growth in the number of EVs in Italy will provide, through vehicle-to-grid technology and smart charging, such a large storage capacity that will decisively contribute to the effective integration of renewables in the electricity system at a relatively low cost.
Enel X is the global business line of the Enel Group dedicated to the development of innovative products and digital solutions in sectors where electricity is showing the greatest potential for transformation. One of Enel X's main missions is the promotion of electric mobility by creating a public and private recharging infrastructure that generates sustainable and shared value for all stakeholders and explores the new opportunities represented by grid balancing and flexibility services.
Nissan, among the world's leading automotive groups, is strongly committed to the development of electric cars. Its participation makes it possible to interact effectively with the on-board batteries and to access to the associated data, both when the car is moving and when it is charging/discharging on the grid.
RSE, a public research company for the electricity and energy sector, has a comprehensive understanding of the functioning of the current and future electricity system. The company has gained broad experience in energy management and in controlling distributed electricity generation and storage resources.
NEW e-mobility | mayo, 24 2019
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redpajama_set_name: RedPajamaCommonCrawl


text:
Q: Deserialize into an object that extends List Using
var serializer = new System.Web.Script.Serialization.JavaScriptSerializer();

the following deserializes my JSON array correctly:
public List<PrintJobTranslation> Translations

and the following doesn't:
public PrintJobTranslations Translations

with
public class PrintJobTranslations : List<PrintJobTranslation>
{
    public string GetTranslation(string Key, string defaultValue)
    {
        var translation = this.FirstOrDefault(x => x.Key == Key);
        if (translation == null) return defaultValue;
        return translation.Translation;
    }
}

It throws the error:

System.Collections.Generic.Dictionary`2[System.String,System.Object] ist kein Wert des Typs Print.printJob.PrintJobTranslation und kann in dieser generischen Sammlung nicht verwendet werden. Parametername: value

I did not find an exact translation, but should be something like this in English:

System.Collections.Generic.Dictionary`2[System.String,System.Object] is not a value of type Print.printJob.PrintJobTranslation and cannot be used in the generic collection. Parameter name: value

How can I get the JSON to deserialize correctly?

A: One way to side step this completely would be to not do that - your method looks fine as an "extension method", so it'll work like an instance method, but without actually having to subclass anything:
public static class PrintJobTranslationExtensions
{
    public static string GetTranslation(
        this List<PrintJobTranslation> list, string Key, string defaultValue)
    {
        var translation = list.FirstOrDefault(x => x.Key == Key);
        if (translation == null) return defaultValue;
        return translation.Translation;
    }
}

and just use List<PrintJobTranslation> in your code.

redpajama_set_name: RedPajamaStackExchange


Welcome home to this lovely 2 story former model home located in Ryegrass Run at Cross Creek. Upgrades galore, beginning with the tastefully adorned coffered ceilings, crown molding and trey ceilings. The kitchen includes upgraded wood cabinets, stone countertops and stainless appliances. Eat-in space in the kitchen includes bay window and seating. The master is tucked quietly away on the first floor with a spacious master bath and huge walk in closet. The downstairs even includes a quiet den and a bath! Upstairs you will find two additional bedrooms, both professionally decorated and a loft housing two built in offices overlooking this immaculate home. All windows are professionally decorated and come with the home. Outdoors include brick paver patio, outdoor kitchen area with grill and a peaceful screened lanai! Paver driveway, Cross Creek is a 694 acre master-planned community, 59% of which is open space. Amenities include a centralized community center featuring an outdoor club room with an adjacent service kitchen and a outdoor covered pavilion, a resort-style pool with water features including a play area and slide; an outdoor amphitheater; a dog park.


The Food | Los Amigos!
We strive to provide great value, healthy food using the best possible ingredients. Our salads and vegetables are collected from Bristol Fruit Market on the day we head off to our event. Our meats come from very happy animals and supplied by our local butcher in South Gloucestershire.
The provenance of our food is really important to us. Our aim is to be as true as possible to the original recipes we found on our travels in the Latin Americas. Our salsas and sauces are made on the morning the day they will be served. All of our foods are free from hydrogenated fats and unnecessary additives & preservatives. As everything is made individually for each customer, all of our menu options are suitable for vegetarians & vegans.
Now, we love all of our food, but we especially love our burritos. We think they are pretty special. Before beginning this adventure we scoured the universe looking for inspiration on ingredients, rolling techniques and spice mixes to marinate our tasty meats in. It was a difficult task but we stuck to it. We coupled this with the knowledge we brought back from countries such as Mexico, Guatemala, Honduras and Peru and thousands of burritos later we are extremely happy with everything we serve, every time. The amount of extras and toppings we offer mean there are hundreds of possible combinations to choose from, our staff are there to coax and cajole the customer into choosing the best possible combinations for the perfect burrito. We see ourselves as the burrito builder and the customer the architect! We love sharing our knowledge of chillis and the origins & history of the food we serve. We know how satisfying a good burrito is and we want to share that with our customers – it's a joint effort!
Our entire kitchen is on show at all times so festival goers can see what's going on and going into our food.


text:
[email protected] • Independent Store News • Midwest
Kingma's Market 'Destination' Opens In Ada Village, Michigan
Alissa Marchat TheShelbyReport
Kingma's Market, a 14,000-s.f. "destination market," has opened in Ada, Michigan, at 444 Ada Drive, with the aim to bring customers a "more intimate shopping experience."
The store features a full-service kitchen, Rowster Coffee café with baristas, a Fish Lads counter with seafood and more. The kitchen offers lunch and dinner, made from scratch. Customers can dine on-site or use the dishes as "market-to-home" meal solutions. The store also features an oyster and sushi bar and a multi-season patio with heaters, allowing customers a place to dine.
The Kingma's Market oyster bar.
Kingma's Ada location is the second for the retailer, which also operates a store in Plainfield. Customers at the new location will find Kingma's fan-favorite provisions, including a wall of bulk candy, nuts, dried fruit and snacks, plus a selection of world cheeses and other delicacies. Kingma's meat counter offers all-natural, local and custom-cut meats and poultry. The store offers a selection of local and domestic craft beers and hundreds of varieties of Michigan, domestic and international wines, and it employs a sommelier.
"Kingma's new location in Ada Village is a tremendous opportunity to expand the brand and be part of a historic village that is undergoing an exciting transformation," said Alan Hartline, a long-time retail executive, who purchased the store from the Kingma family in 2014.
"Today marks an important day in the history of Kingma's Market, as one of the region's iconic brands, we have the privilege of being part of the fabric of Grand Rapids and now we have the opportunity to broaden that reach to surrounding communities," he said. "We look forward to the opportunity to bring our unique shopping experience to Ada Village.
"Kingma's Market offers the best of both worlds—a farm fresh market and a retail grocery. We are creating a unique, simplified shopping experience for our customers, offering the ultimate in food, fun, exploration and innovation.
"Our brand promise is to feature an extensive offering of local, Michigan-made products; more than half of our inventory comes from Michigan businesses. Kingma's hyper-local sourcing will provide customers with fresh, just-harvested fruits and vegetables like spinach, kale, leaf lettuces, beets, tomatoes and more."
Kingma's is anchoring a growing number of Ada Village shops, restaurants and new businesses as Ada's redevelopment continues.
"We are thrilled as new investors continue to show interest in Ada Village and are pleased to welcome Kingma's Market to our wonderful community as the redevelopment continues," said George Haga, Ada Township Supervisor.
Kingma's Market will be open Monday through Saturday from 7 a.m. to 8 p.m., and Sunday from 9 a.m. to 6 p.m.
The Plainfield location will have the same hours and now is open on Sundays.
Kingma's Market was originally founded by the Kingma family, first located in the Boston Square area and then moving to 2225 Plainfield Ave. in Grand Rapids.
Tags[email protected] Kingma's Market local Michigan Midwest
Wisconsin Schedules Its First-Ever Art Of Cheese Festival
Frieda's Celebrates Life Of Kiwi Queen, Dr. Frieda Rapoport Caplan
Alissa Marchat
A word nerd and a grocery geek. She is a proud new homeowner and a great lover of avocado toast.
Charles Butt Donates $5 Million To J.J. Watt Foundation For Disaster Relief
SpartanNash Foundation, Shoppers Raise $260K For Hunger Relief


This is what I think would be great for all of us to have!
It would be made out of acyrilic and mounted with UFO on the inside.
I don't know if you guys get alot of theft to your vehicles, but If I were to steal the UFO, it wouldn't take me long to find out a way to get it off of someone's car, then break in and find the controller, i think.
By having this, it would be mounted the same way, but with added security and easy to clean. They would have to take this off, then take your UFO's off - way to much time!
Also, drain holes would be drilled on the bottom to let any water excape, if not fully sealed on top.
I figure, if I'm gonna spend the money of having the best kit under my ride, I would like to have added protection.
Also, I don't have the UFO yet, But when I get it, I will be having someone make this for my UFO kit!
What are you suggesting to be used to go over the tubes that are screwed down? I agree that security is needed with the tubes, is easy to get them off anyones car as they're only held on with cable ties.
The name of it is Hose Clamps. I am going to use those on my truck, but not many ppl would know how to put it on. I will be welding it on!!
As for the tubes, I know they wont work without controller, but if someone gets in, then your screwed.
Just posted it for a future idea of something to make for protection.
1 more thing, instead of clear acyrlic plastic, you could use transparent, i think thats it. It would break up the light more, but not shine as far, unless it was a clear type.
Also, sometimes, when thieves can't get what they want, they wind up either accidentally, or intentially destroying the vehicle. They would probably smash the tubes if they couldn't get them off.
I had a hard enough time find spots to put screws in for the zip-tie mounts. I'm not sure I could find (or be willing) that many spots to put screws in the undercarriage.
They would probably smash the tubes if they couldn't get them off..
LMAO, That is so true, they don't want to leave a half of a doughnut just lying there, where ever they are!


A discussion on security policies at the Infosec World conference in Orlando suggested focus and simplicity are key elements in developing and implementing companywide information security policies.
Anish Bhimani, chief information security officer at JPMorgan Chase, urged companies to "be crystal clear what your objectives are" and spell them out in a policy that is easily read and understood by other workers, while avoiding developing a "laundry list" of overly specific compliance items that will be hard to enforce.
JPMorgan Chase has adopted a relatively short list of "must comply with" information security policy items that incorporate the company's high-level data protection goals, but has implemented a broader set of "should comply with" items that are more difficult to meet.
Security policies need to be easily enforceable to be effective, according to Philip Maier, vice-president of the information security, emerging technology and network group at Inovant, which is Visa's IT unit. He suggests vetting all policies with an enforcement group to ensure there's a realistic way for them to be enforced.
Another issue for multinational companies with global operations is to write security policies that retain the same meaning across different languages.
Security policies are the area of security that are most forgotten by companies, yet are often the most important. Some clear advice from JPMorgan Chase and Visa is welcome.


Little Stranger is always a great hit with every crowd. Dynamic Tickets has access to a wide variety of tickets to every Little Stranger show. No matter what your budget is, you will find the right seats here!
Can't find the Little Stranger tickets you want?
Shop by phone! Call 1-800-583-TIXX (1-800-583-8499) and speak directly with one of our ticket specialist to find tickets to the upcoming Little Stranger Rap / Hip Hop event.


text:
Q: Can I use ${file} to generate a output "arg" for a task in vscode? I'm trying to build files in vscode with an "unsupported" compiler. Therefore I've created a task to start the compiler and this works perfectly, as long as the source and destination files are given. I give my source file as ${file} and vscode correctly substitutes this with the source file. For the destination file I have to use the same filename but change it's extension.
Is it possible for me to create a string variable in .json, copy the value of my ${file} string into that and use change its extension before using it as an argument?
My tasks.json is below, my sourcefile ${file} = "C:\_projects\Customer\Logging\LogAsync\ASyncLog\Server.kl"
{
    "version": "2.0.0",
    "tasks": [
        {
            "label": "Build",
            "type": "shell",
            "command": ".\\ktrans.exe",
            "problemMatcher": [],
            "options": {
                "cwd": "C:\\Program Files (x86)\\FANUC\\WinOLPC\\bin\\"
            },
            "args": [
                "${file}",
                "C:\\_projects\\Customer\\Logging\\LogAsync\\ASyncLog\\Server.pc"
            ],
            "group": {
                "kind": "build",
                "isDefault": true
            }
        }
    ]
}

A: Thanks all for helping. My working code is below for other peaple who came here searching for how to compile Fanuc Karel in vscode:
{
    "version": "2.0.0",
    "tasks": [
        {
            "label": "Build",
            "type": "shell",
            "command": ".\\ktrans.exe",
            "problemMatcher": [],
            "options": {
                "cwd": "C:\\Program Files (x86)\\FANUC\\WinOLPC\\bin\\"
            },
            "args": [
                "${file}",
                "${fileDirname}\\${fileBasenameNoExtension}.pc"
            ],
            "group": {
                "kind": "build",
                "isDefault": true
            }
        }
    ]
}

A: Yes, you can use ${file} to generate an output "arg" for a task in vscode. To do so, simply add the following line to your tasks.json file:
"args": ["${file}"]


Like nothing else, cycling allows you to uncover unique and hidden aspects of a region and its culture. You'd never experience this from a rental car, tour bus or cruise ship. You can decide on whim to explore a winery, stop for a long lunch or venture even further on a quiet road. Travelling by bicycle leads to authentic connections with a region, it's people and a lifetime of memories. If you are willing to slow down and encounter a little adventure while riding throughout some of Europe's finest cycling regions, then you are ready for the incomparable pleasure of a cycling holiday with CycleVentures.
We'll provide services to make your trip as seamless and wonderful as possible; little things that you won't notice and more obvious ones too. As always, our guides and our support van are there when you need them.
After over four decades of active travel by bicycle we look forward to the next trip as if it was our first.
Comprehensive trip planning, a well-designed itinerary and excellent riding routes.
Airport pick-up and drop off on scheduled days.
Expert leadership: two leaders per trip with groups of seven or more.
Welcome Reception on the first day of each trip.
GPS tracks for all main routes that can be transferred to riders' personal computers.
Michelin maps and route description with profiles for all riding days.
Optional add-on features like wine tasting or guided walking tours (depending on trip).
Detailed pre-departure information and trip extension assistance.
Daily support vehicle with water and snacks.
Daily luggage transport and land transportation stated in the itinerary.
Accommodations: Three star hotels (occassional two-star or inn) based on double occupancy with private facilities unless otherwise stated.
Daily map session reviewing the next day's ride.
Bike box storage during the trip or transfer to finale destination if a point-to-point trip.
Assistance with bike rentals: booking, delivery and return.
Optional masseuse/soigneur, riding coach on private departures.
Here are just a few of our guides that are ready to show you their culture, stunning scenery and amazing trails on your next Big Mountain Bike Adventures' trip.
An Italian in Norway?! Andreas' deep passion for Narvik and the Lofoten Islands is evident as he rings off names of all the peaks, shares stories of local legends and knows the region's history intimately. He is one of the only mountain bike guides in the Lofoten and we're lucky to work with him. In the Dolomites he is in his backyard. His enthusiasm and energy is infectious and his high level of organization and guiding is welcomed, to be hosted by Andreas is nothing but a pleasure.
We are so very fortunate to have Nicolas & Vicente and their team at the helm of our Peru trip. They exude all the attributes that we seek in a professional mountain bike guide: they're kind and respectful, passionate about sharing their country with riders, helpful and patient, highly organized and detail oriented and very importantly they love to ride mountain bikes! To ride with these guys in the Peruvian Andes is a once-and-a-lifetime opportunity.
Raised with Michelin maps of France strewn across the kitchen table and parents discussing logistics for month-long European cycling trips with a group of 25 cyclists, Chris was born into planning and developing bike trips. He is passionate about travel, adventure, culture, sharing amazing experiences and really fun singletrack riding.
Born and bred in Italy's South Tyrol, Werner quit his office job in 2013 to become a full-time mountain bike skills coach and professional guide. A passionate rider and nature lover with a character that'll make you smile inside and out, there is no better guide than Werner to show you the beautiful trails, culture and mountains of the Dolomites along with it's delicious cuisine & fine wine.
Based in beautiful Pemberton, BC, Emily is at home in the mountains. Specifically, she's at home riding her bike in big and remote mountains; guiding & coaching riders, exploring with friends and winning enduro races like the four-day Trans-Cascadia. She's one of the best mountain bikers you'll ever ride with, as humble and friendly as can be and a true professional guide.
There is simply no one better than Paulo to show you real Costa Rican singletrack mountain biking. Wicked, technical and big trails that even locals don't know about. Beneath Paulo's layed back and soft-spoken demeanor is a strong rider both up and down, a kind person and consummate professional on all aspects of a great mountain bike adventure.
Swedish organization meets Italian passion! This wife & husband team will peel away Liguria's layers to unveil its sweet secret spots from the best gelato, pesto & espresso to the the best local shuttles on hidden trails tucked away high in the forested mountains. One of the strongest enduro riders in Europe, Louise shares with our riders her secrets to riding well. Louise & Alessandro: the A team for any trip!
Lausanne-based Myriam grew up doing activities in the Swiss mountains. She was professional mountain bike racer from 2007-2011 and today she spends her time as a sports trainer, mountain bike coach, skills coach and professional guide. Let Myriam show you her amazingly beautiful big mountain backyard.
A professional mountain bike guide and true lover of her native Iceland, there is no one more qualified than Anna to share with you this beautiful island, from it's wide-open and rugged natural landscapes to its unique and quirky character that'll surely surprise you.
Meet Prayash, our local super star guide. Mountain biking has been a passion for him since mid 2000's. He took it next level, after opening a bike shop in 2009 and eventually becoming a professional MTB guide. "My favourite part of mtb biking is without a doubt getting to explore my country and getting to meet different bikers from all over the world. I personally have ridden bikes in Asia; like India, Singapore, Thailand, Korea, and more. I also value my time as a volunteer on Nepal MTB team as a coach.


Independent Liverpool bar group Graffiti Spirits Group launched its Christmas themed pop-up this week, Miracle on Seel Street.
Popping up until January, Miracle on Seel Street invites guests to escape the cold and take refuge in the intimate surroundings while enjoying cocktails such as the Smoked Old Fashioned, which combines Bulleit Bourbon with sugar, bitters and festive spices.
Diageo Reserve has sponsored the pop up and all of the bar's mouth-watering cocktails have been crafted with spirits from the group's portfolio.


Our product training is part of our 'More than adhesives' promise. At Apollo Adhesive Solutions, we are committed to ensuring that you have the product knowledge you need for the successful completion of your project, whether this be onsite or in the factory.
Our adhesive product training is both theory-based and practical. We set high-quality requirements, which make it vital to ensure that the skills and experience of our employees and customers are kept updated. Our partners receive extensive training, focused on application, design and execution, making them experts in the installation of Apollo Adhesive Solutions products and systems. Training content can be tailored and agreed by all parties in advance; it can be adapted to suit commercial or technical employees.
A key focus for Apollo Adhesive Solutions is to ensure our customers know how products, application and design standards are interrelated, in order to provide advice and guidance on solutions. We therefore hold regular courses to ensure that we and our partners have the most up-to-date skills and information. Our courses are hosted by our Technical and Marketing teams at Apollo's Headquarters in Tamworth, Staffordshire.
Please contact sales or marketing for more information.


text:
UK Cities
UK Landscapes
World Landscapes
Landscape Courses
Darkroom Workshops
Professional Masterclasses
My other work
[ti_wishlist_products_counter] 0123 456789
Our coolest product
PEAK LIGHT – The Peak District Photography of Dave Butcher. Sold Out
The Peak District stretches from near Ashbourne in the South to near Holmfirth in the north, a distance of about 50 miles, and from Macclesfield in the West to Chesterfield in the East, about 30 miles.
Peak Light is sold out.
Category: Books & Writing Tag: Scotland
Peak Light is available at the reduced price of £12 while stocks last. The price includes UK shipping. There is a charge for shipping outside the UK. All copies ordered here are signed by the author.
Created in 1951, it was the first National Park in the UK and is, allegedly, the second most visited National Park in the world after Yellowstone in the USA – the reason for this being that it is surrounded by large towns and cities.
There are no soaring peaks like those in the Lake District, Snowdonia or the Scottish Highlands, but this is more than compensated by the varied countryside.
There are two distinct areas called White Peak (after the limestone dales in the south) and Dark Peak (peat bog country in the north and west) – and they are very different in character.
The Limestone dales are often steep-sided gorges, enclosing a fast running river or stream, with the odd peak, spire, cave and arch, often linked by wider areas of farmland and grazing. Between the dales is rolling grassy farmland divided by the ubiquitous dry stone walls with small copses of trees breaking the skyline at intervals. Dove Dale is probably the most famous of all of the Derbyshire Dales, but is just 2 or 3 miles of the 45 miles' length of the River Dove, from its source on Axe Edge near Buxton. Each short section of Dale that it runs through has a different name.
Peat bog country, on the other hand, is more rolling, covered in brown peat, heather and tussocky grasses. The purple heather looks fantastic in late August in the sunshine. Once again, there are dry stone walls everywhere and streams and rivers that run pretty reliably, as might be expected in an area that receives up to 2 metres of rainfall a year.
The highest areas are here too, with the summit of Kinderscout at 636m (2087 ft) being the highest point in Derbyshire, although I use 'summit' in the broadest sense of the word: it really is not obvious when you reach the top of this immense peat bog area. This is also the location of the highest waterfall in Derbyshire, Kinder Downfall at 30m (100 ft). This dries up in the summer as the River Kinder is absorbed by the peat before it reaches the falls.
Peak Light is roughly arranged geographically from south to north. The position of each location is shown on the map on page 4 and this, together with the caption for each picture, will help you to follow in my footsteps.
The photographs concentrate on the landscapes rather than the many villages and even with this focus, space limitations may mean I have still omitted some places that you would have liked to be included.
Since 1988, I have lived in the small village of Tunstead Milton, between Whaley Bridge and Chapel-en-le-Frith, towards the north of the Peak District. The immediate area is great for solitary walking since it is not as visited as some in the Peaks, although the scenery is just as spectacular to my eyes.
I hope these images of the Peak District will inspire you, as much as it does me, to visit and enjoy the area in all of its varied seasons.
Dave Butcher
If you want to find a copy through secondhand bookshops quote: ISBN 978-009555627-0-9
Flick through a few pages of Peak Light:
To help you decide here are some reviews from various publications.
Black and White Photography magazine
Cheshire Life
Peak District Life magazine
High Peak Review
John Muir Trust Journal
Peak Advertiser
CITY LIGHT and LAND LIGHT Bundle
Jura Paps Reflection
LAND LIGHT – Landscapes of the World
World Landscapes (525)
UK Cities (394)
UK Landscapes (190)
World Cities (458)
Books & Writing (10)
All images are copyright © Dr. Dave Butcher and may not be downloaded, copied or reproduced in any way without prior written permission. All rights are reserved.
Get some free printing and developing tips, tutorials and information from the expert over at Darkroom Dave!
Discover the natural colours of the city, landscape and still life at Jan Butcher Photography…
books by Dave Butcher
© Copyright Dave Butcher Photography 2017 All Rights Reserved
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Check this link if you want to restore your iTunes library backup file on Mac.


text:
Team Bolt
usainbolt.com
Usain will run 200m in Herculis, Monaco
April 10, 2012 790 comments
Monte-Carlo – Usain Bolt will return to Monaco to run the 200m at the Herculis Samsung Diamond League meeting on 20 July 2012.
The series of 14 meetings spread across Asia, Europe, the Middle East and the USA which compose the 2012 Samsung Diamond League season gets underway in just under a month's time in Doha, Qatar on 11 May.
After last year's success in the Principality over 100m (9.88 sec; 22 July 2011), Bolt is eager to return to Monaco for what will be his last race before the Jamaican superstar competes to defend his sprint titles at the London Olympic Games.
The reigning 100m and 200m Olympic champion and World record holder is scheduled to line-up in his favourite event at the Herculis meeting.
Last year, following his now famous false start in the 100m, Bolt defended his World Championships title at 200m in an amazing time of 19.40 and later added another gold and World record in the 4x100m relay.
Could the Herculis meeting record of 19.72 set by Tyson Gay in 2010 be in danger from the 25-year-old Jamaican who has recorded nine sub 19.70 secs times for the 200m in his career topped by his World record of 19.19 (20 Aug 2009)?
"Monaco will be my last race before the Olympics and I am looking forward to putting on a great show for the fans. It is going to be my second time racing in Monaco. I love the city and the weather is always good," commented Bolt.
Today's announcement of Bolt's participation in Monaco follows earlier confirmations that he will also run in the Oslo and Rome meetings of the 2012 Samsung Diamond League.
'Living The Dream' Usain Bolt & NJ
21 rural schools get donation of supplies from Usain Bolt Foundation
13th November 2020 – Report from jamaicaobserver.com — Twenty one early childhood institutions (ECIs) in Trelawny, St Ann, St James, St Elizabeth and Clarendon have benefited from a donation of...
Puma x Usain Bolt Ralph Sampson trainers available on puma.com
3rd October 2020 – Puma x Usain Bolt Ralph Sampson trainers are now available on puma.com https://eu.puma.com/uk/en/pd/puma-x-usain-bolt-ralph-sampson-trainers/380202.html?dwvar_380202_color=01
Copyright 2020 Usain Bolt


text:
Moulin Rouge: History Behind Pigalle's Red Cabaret
22 August 2011 by Anna Meakin 14302
Visitors waiting on line for admission to the Moulin Rouge may be forgiven for not noticing the Histoire de Paris building plaque, which they still might not understand even if they noticed and then took the time to try to translate it. They'd be left with baffling references to "Oller and Zidler," a "White Queen," a giant wooden elephant, a "Dream of Egypt" and someone called "Missy." This incomprehensible text was one of the reasons we chose to write Paris by Plaque, and to adopt the strap-line "All will be revealed…". The stories we found hidden within these plaques are, quite simply, enchanting. No translation of them had been published, however, let alone with an explanation of the content. So we wrote it ourselves, starting with Le Moulin Rouge. Next time you pass the entrance to this famous cabaret, allow your mind to drift back 120 years. The date is 1889, and two businessmen, Joseph Oller and Charles Zidler, are planning a new venture. Impressed with the commercial success of the wildly popular dances at the Élysée Montmartre, the pair decided to open a rival dance hall in the run-down area of Pigalle. Even at their most optimistic they could not have imagined that the enterprise would become one of the most visited tourist attractions in Paris over a century later. Oller and Zidler took a gamble in buying the old White Queen Dance Hall (La Reine Blanche) with its crumbling, peeling façade and seedy reputation to match the surrounding area. In need of total renovation, the White Queen was an unlikely venue for a rival to the Élysée, which had cornered the market in the wild and risqué dances that drew the crowds. The Can-Can we are familiar with today developed out of these wild quadrilles, typified by women somewhat lacking in the underwear department, whirling their skirts around in a dizzying high-energy dance display. Undeterred, Oller and Zidler set to work and with bold showmanship they erected the huge wooden windmill above the entrance and painted it red. Over the years this red windmill (moulin rouge) was to become an icon of Parisian nightlife. Emblematic of Montmartre's rural past—when windmills dotted the hills around Paris—the red windmill with its slowly turning sails intrigued dancehall regulars. Queues began to form. Oller and Zidler's next business coup was to poach the top dancer from the Élysée Montmartre, one Louise Weber, or La Gouloue (The Glutton) as she was known for her love of alcohol. She was the wildest, most outrageous and daring of the dancers and a huge favorite with crowds. Fiercely provocative in her dancing style, she would swirl past tables, snatching drinks off patrons' tables and whisking their hats off with her high-kicks. She was soon the main attraction at The Moulin Rouge too and her show, with her extraordinarily limber dance-partner Valentin "The Boneless," was the hottest ticket in town. Toulouse-Lautrec was a nightly visitor to the venue and it was here that he sat watching while drawing some of his most famous images of Paris nightlife. Louise, Valentin and their successor, Jane Avril, all feature in his paintings and posters from this time. More drama was to follow from Oller and Zidler. They purchased a huge wooden elephant from the Exhibition Universelle (World's Fair) of 1900 and installed it in the gardens. They made a spiral staircase entrance to it inside one of the legs and, on a stage housed in its stomach, dancers would perform sensual belly dances for a male-only audience. Later this elephant would feature in the contemporary Hollywood musical film Moulin Rouge, as a setting for Nicole Kidman and Ewan McGregor's love story. Back in 1907, however, a million miles from Hollywood glamour, the Moulin Rouge continued to provoke and challenge. The semi-nude dancing sometimes gave way to a provocative show of another kind, such as the "Dream of Egypt," put on by the writer Colette and her girlfriend, Mathilde de Morny, or "Missy," as she was known. Colette dressed herself as an Egyptian mummy and had Missy, dressed as a male archeologist, unwrap her. They finished the scene with an amorous kiss. The audience—made up mostly of Mathilde's outraged aristocratic brother and a mob of his friends—were so outraged by the spectacle that they rushed the stage, forcing the performers to run and lock themselves in the box office until the police arrived. Take a little time to visit the Museum of Montmartre, where you will see some original posters by Toulouse-Lautrec. His depictions of dancehall nightlife live on in our memories so powerfully. Today dancer Louise Weber lies buried in the Cimetière de Montmartre where there are usually fresh flowers on her grave. Something of her energy and daring still touches us through the passage of time, and the promise of the thrill she engendered still draws visitors by the thousands to see the Moulin Rouge today. But next time you pass the entrance and its plaque, just let your mind drift back…
Visitors waiting on line for admission to the Moulin Rouge may be forgiven for not noticing the Histoire de Paris building plaque, which they still might not understand even if they noticed and then took the time to try to translate it. They'd be left with baffling references to "Oller and Zidler," a "White Queen," a giant wooden elephant, a "Dream of Egypt" and someone called "Missy."
This incomprehensible text was one of the reasons we chose to write Paris by Plaque, and to adopt the strap-line "All will be revealed…". The stories we found hidden within these plaques are, quite simply, enchanting. No translation of them had been published, however, let alone with an explanation of the content. So we wrote it ourselves, starting with Le Moulin Rouge.
Next time you pass the entrance to this famous cabaret, allow your mind to drift back 120 years. The date is 1889, and two businessmen, Joseph Oller and Charles Zidler, are planning a new venture. Impressed with the commercial success of the wildly popular dances at the Élysée Montmartre, the pair decided to open a rival dance hall in the run-down area of Pigalle. Even at their most optimistic they could not have imagined that the enterprise would become one of the most visited tourist attractions in Paris over a century later.
Oller and Zidler took a gamble in buying the old White Queen Dance Hall (La Reine Blanche) with its crumbling, peeling façade and seedy reputation to match the surrounding area. In need of total renovation, the White Queen was an unlikely venue for a rival to the Élysée, which had cornered the market in the wild and risqué dances that drew the crowds. The Can-Can we are familiar with today developed out of these wild quadrilles, typified by women somewhat lacking in the underwear department, whirling their skirts around in a dizzying high-energy dance display.
Undeterred, Oller and Zidler set to work and with bold showmanship they erected the huge wooden windmill above the entrance and painted it red. Over the years this red windmill (moulin rouge) was to become an icon of Parisian nightlife. Emblematic of Montmartre's rural past—when windmills dotted the hills around Paris—the red windmill with its slowly turning sails intrigued dancehall regulars. Queues began to form.
Oller and Zidler's next business coup was to poach the top dancer from the Élysée Montmartre, one Louise Weber, or La Gouloue (The Glutton) as she was known for her love of alcohol. She was the wildest, most outrageous and daring of the dancers and a huge favorite with crowds. Fiercely provocative in her dancing style, she would swirl past tables, snatching drinks off patrons' tables and whisking their hats off with her high-kicks. She was soon the main attraction at The Moulin Rouge too and her show, with her extraordinarily limber dance-partner Valentin "The Boneless," was the hottest ticket in town. Toulouse-Lautrec was a nightly visitor to the venue and it was here that he sat watching while drawing some of his most famous images of Paris nightlife. Louise, Valentin and their successor, Jane Avril, all feature in his paintings and posters from this time.
More drama was to follow from Oller and Zidler. They purchased a huge wooden elephant from the Exhibition Universelle (World's Fair) of 1900 and installed it in the gardens. They made a spiral staircase entrance to it inside one of the legs and, on a stage housed in its stomach, dancers would perform sensual belly dances for a male-only audience. Later this elephant would feature in the contemporary Hollywood musical film Moulin Rouge, as a setting for Nicole Kidman and Ewan McGregor's love story.
Back in 1907, however, a million miles from Hollywood glamour, the Moulin Rouge continued to provoke and challenge. The semi-nude dancing sometimes gave way to a provocative show of another kind, such as the "Dream of Egypt," put on by the writer Colette and her girlfriend, Mathilde de Morny, or "Missy," as she was known. Colette dressed herself as an Egyptian mummy and had Missy, dressed as a male archeologist, unwrap her. They finished the scene with an amorous kiss. The audience—made up mostly of Mathilde's outraged aristocratic brother and a mob of his friends—were so outraged by the spectacle that they rushed the stage, forcing the performers to run and lock themselves in the box office until the police arrived.
Take a little time to visit the Museum of Montmartre, where you will see some original posters by Toulouse-Lautrec. His depictions of dancehall nightlife live on in our memories so powerfully. Today dancer Louise Weber lies buried in the Cimetière de Montmartre where there are usually fresh flowers on her grave. Something of her energy and daring still touches us through the passage of time, and the promise of the thrill she engendered still draws visitors by the thousands to see the Moulin Rouge today.
But next time you pass the entrance and its plaque, just let your mind drift back 120 years…
Tél: 01 5309 8282
82, boulevard de Clichy, Paris 18th
Métro: Line 2, Blanche
Anna Meakin is the author of Paris by Plaque – Montmartre Vol 1 (The Complete Guide to the Historic Plaques of Paris) and this is her first article for BonjourParis. Paris by Plaque is available at her website, the Museum of Montmartre and here at our Amazon.com Boutique.
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