Abstract:
:Although 5-fluorouracil (FUra) has been the drug of choice for the treatment of patients with advanced colorectal carcinoma, the response rates are in the range of 15% and the median survival times do not exceed 9 months. Interferon alpha (IFN alpha) has limited antitumour activity in this disease. Recent clinical trials have demonstrated that both the response rate and the survival time of patients with advanced colorectal cancer can be significantly improved by the addition of leucovorin (CF) to FUra. In a randomized phase III trial, the median response to FUra and CF was about 30% with a range of 20-55%, dependent on the dose and schedule of administration of CF. Due to multiplicity of mechanisms of action postulated for IFN alpha, the role of IFN alpha in the modulation of the cytotoxicity and therapeutic efficacy of FUra alone and in combination with CF has been evaluated in patients with advanced colorectal cancer and also in a variety of human cell lines in culture, including human colorectal cell lines, HCT-8, human bladder cell line RT-4 and leukaemia CEM cells. The results obtained in patients demonstrated that indeed the antitumour activity of FUra can be improved by the addition of IFN alpha with a response range from 26% to 76%. The initial clinical use of this combination, however, has been limited in some cases by the severe host toxicity. In vitro results demonstrated that: (1) in vitro cytotoxicity potentiation by IFN alpha is cell-type dependent; (2) in these cells where modulation was possible, alpha IFN was used as a low and noncytotoxic doses (10-50 micrograms/ml for 3-5 d exposure), and (3) the cytotoxicity of IFN alpha was dose dependent, indicating a direct antiproliferative cellular effect.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Rustum YMdoi
10.1111/j.1365-2141.1991.tb08120.xsubject
Has Abstractpub_date
1991-10-01 00:00:00pages
52-5eissn
0007-1048issn
1365-2141journal_volume
79 Suppl 1pub_type
杂志文章abstract::A patient with apparent anaemia and thrombocytopenia caused by a monoclonal paraprotein is described. The patient's serum contained a monoclonal IgM kappa, a cryoglobulin and a cold agglutinin. The cryoglobulin, similar to the serum paraprotein, was a monoclonal IgM kappa. Serum was studied to determine the relationsh...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00586.x
更新日期:1998-03-01 00:00:00
abstract::A 2-year-old girl is described with severe haemophilia A (factor VIII: C < 0.01 units/ml). Both of her parents were phenotypically normal. Cytogenetic analysis on the proband demonstrated an interstitial X chromosome deletion encompassing Xq26-q28. Molecular studies with several polymorphic markers close to and within...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1995.tb05213.x
更新日期:1995-08-01 00:00:00
abstract::A simplified method of International Normalized Ratio (INR) derivation using linear regression of certified INR plotted against local prothrombin time (PT) results has been compared with INR from conventional orthogonal regression. Linear regression assumes error only with the local PT results whereas orthogonal regre...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1046/j.1365-2141.1997.d01-3498.x
更新日期:1997-09-01 00:00:00
abstract::The determinants of steady state haemoglobin levels in sickle cell-haemoglobin C (SC) disease were investigated by measuring routine haematological and biochemical indices, red cell survival, oxygen affinity, pitted erythrocytes, and red cell and plasma volumes in 31 adult patients (15 male; 16 female). Red cell survi...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1979.tb03718.x
更新日期:1979-09-01 00:00:00
abstract::We report a patient with hypereosinophilic syndrome (HES), which, 8 years later, transformed into granulocytic sarcoma in the brain and, subsequently, into acute myelocytic leukaemia. Repeated chromosome analyses showed a normal karyotype, until the time of leukaemic transformation when trisomy 8 was confirmed in cell...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03922.x
更新日期:2002-12-01 00:00:00
abstract::Acute promyelocytic leukaemia (APL) is a rare subtype of acute myeloid leukaemia. The outcome of paediatric APL has improved substantially over the past 20 years; cure rates above 80% are expected when all-trans retinoic acid (ATRA) is given with anthracycline-based regimens. The presenting features of paediatric APL ...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.12584
更新日期:2014-01-01 00:00:00
abstract::A reduction of donor effects during centrifugal plateletpheresis with the Haemonetics Blood Processor was achieved by reducing the concentration of the citrate anticoagulant. Serum citrate and ionized calcium levels, immediately and 1 h post-pheresis, were affected to a lesser extent by using 5.0 g total ionized citra...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1976.tb03585.x
更新日期:1976-11-01 00:00:00
abstract::Peripheral blood mononuclear cells (PBMNC) from 23 healthy subjects and 39 patients with B-cell chronic leukaemia (B-CLL) were assayed for ribonuclease H activity using as substrate the filter-immobilized synthetic homopolymer hybrid 3H-poly(rA):poly(dT). In 69% of the leukaemia patients examined enzyme activities wer...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1988.tb02486.x
更新日期:1988-11-01 00:00:00
abstract::Platelet antibodies either bound to the surface of platelets or free in the serum were sought in patients who had low platelet counts for a variety of reasons. They were detected by finding excess IgG on the surface of washed platelets either directly or after incubation of the serum with normal platelets. The techniq...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1977.tb00567.x
更新日期:1977-01-01 00:00:00
abstract::Factor VIII (FVIII) inhibitors appear in 3-20% of haemophilia A patients after injection of FVIII concentrates. However, autoantibodies to FVIII are also reported in non-haemophiliacs. In these patients FVIII inhibitor disappears spontaneously or diminishes in response to immunosuppressive therapy. However, a few pati...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01220.x
更新日期:1999-03-01 00:00:00
abstract::Data on outcome, prognostic factors, and treatment for very elderly non-Hodgkin lymphomas (NHL) is sparse. We conducted a multicentre retrospective analysis of NHL patients ≥80 years (at diagnosis) treated between 1999 and 2009. Detailed characteristics were obtained including geriatric syndromes, activities of daily ...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2141.2011.08934.x
更新日期:2012-01-01 00:00:00
abstract::Ninety consecutive patients with acute promyelocytic leukaemia were investigated for promoter methylation of CDKN2B (alias p15) and CDKN2A (alias p16) in disease relapse and progression. CDKN2B methylation was significantly more frequent at first relapse (30/36, 83%) than at presentation (48/77, 62%) (P=0.025), while ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2005.05818.x
更新日期:2005-12-01 00:00:00
abstract::Elevated plasminogen activator inhibitor 1 (PAI-1) levels are associated with venous thromboembolism, although their significance is unclear. PAI-1 levels are influenced by a PAI-1 promoter dimorphism (4G/5G), the 4G allele being associated with increased PAI-1 activity. We investigated whether the 4G allele influence...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02152.x
更新日期:2000-07-01 00:00:00
abstract::The availability of a preparation of recombinant human erythropoietin (rEp) prompted us to investigate the role of Ep in the regulation of megakaryocytopoiesis in mice, using experimental procedures by which the effects on the mitotic and post-mitotic compartment of megakaryocytes could be evaluated separately. In aga...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1989.tb06303.x
更新日期:1989-04-01 00:00:00
abstract::During definitive erythropoiesis, erythroid precursors undergo differentiation through multiple nucleated states to an enucleated reticulocyte, which loses its residual RNA/organelles to become a mature erythrocyte. Over the course of these transformations, continuous changes in membrane proteins occur, including shif...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2010.08268.x
更新日期:2010-09-01 00:00:00
abstract::The Abl kinase inhibitor STI571 (imatinib mesylate) induces haematological remissions in many patients with chronic myeloid leukaemia (CML) but advanced stage CML usually becomes resistant to STI571. We describe a patient in whom progressive resistance to STI571 correlated with the appearance of a mutation in the Bcr-...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03708.x
更新日期:2002-10-01 00:00:00
abstract::Shwachman-Diamond Syndrome (SDS) is a multi-system genetic disorder with bone marrow failure. SBDS, the gene associated with SDS, has been postulated to play a role in ribosome biogenesis and RNA processing, but its functions are still unknown. To study whether these pathways are interrupted when Sbds protein is lost,...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2009.07692.x
更新日期:2009-06-01 00:00:00
abstract::Among 750 previously untreated patients with multiple myeloma, 27 (4%) presented with plasma cell leukaemia. All but one patient had high tumour mass and, when compared with comparable patients without leukaemia, more frequent extraosseous involvement, thrombocytopenia, high serum lactate dehydrogenase and hypodiploid...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2141.1994.tb05114.x
更新日期:1994-12-01 00:00:00
abstract::Myelodysplastic syndromes (MDS) and the mixed myelodysplastic/myeloproliferative disorder juvenile myelomonocytic leukaemia (JMML) are rare haematopoietic stem cell diseases in children. While MDS-initiating events remain largely obscure, a growing body of clinical, genetic and laboratory evidence suggests that JMML i...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2007.06958.x
更新日期:2008-03-01 00:00:00
abstract::The prognostic significance of cytogenetic abnormalities was determined in 106 patients with well-characterized idiopathic myelofibrosis who were successfully karyotyped at diagnosis. 35% of the cases exhibited a clonal abnormality (37/106), whereas 65% (69/106) had a normal karyotype. Three characteristic defects, na...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.1722990.x
更新日期:1997-07-01 00:00:00
abstract::To investigate the role of neutrophils in complement-induced changes in vascular permeability, skin wheal and flare responses to intradermal injection of autologous activated serum complement were measured in normal and neutropenic subjects. In normal subjects, responses were dose-dependent and were abolished by remov...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1986.tb04131.x
更新日期:1986-10-01 00:00:00
abstract::Twenty adult patients with high-risk leukaemia underwent allogeneic haemopoietic stem cell transplantation after melphalan, busulphan and total body irradiation followed by short-term methotrexate and low-dose cyclosporine or tacrolimus. Three patients developed veno-occlusive disease and no patient developed renal dy...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01424.x
更新日期:1999-06-01 00:00:00
abstract::During periods of immunosuppression, such as postallogeneic stem cell transplantation (SCT), patients are at significant risk for severe viral infections. Human adenovirus (HAdV) infection is a serious complication post-SCT, especially in children. Virus-specific T cells are essential for the clearance of HAdV, as ant...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2006.06108.x
更新日期:2006-07-01 00:00:00
abstract::Down syndrome (DS) children are at an increased risk of developing myelodysplasia and acute myeloid leukaemia (AML). We retrospectively analysed the population-based data on 81 children with myeloid leukaemia of Down syndrome (ML-DS) from the UK National Registry of Childhood Tumours and experience in the Medical Rese...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/j.1365-2141.2005.05906.x
更新日期:2006-03-01 00:00:00
abstract::When stimulated in vitro, human platelets release matrix metalloproteinase-2 (MMP-2) that, in turn, potentiates platelet activation. The present study investigated if MMP-2 is released from activated platelets in vivo in humans and whether aspirin inhibits this release. MMP-2 levels were measured by zymography, immuno...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2007.06632.x
更新日期:2007-07-01 00:00:00
abstract::We have identified a tissue kallikrein in polymorphonuclear (PMN) leucocytes of normal human blood and bone marrow by immunocytochemistry, radioimmunoassay and enzymology. Immunoreactive tissue kallikrein was visualized in the mature neutrophil leucocytes and in immature forms such as metamyelocytes and myelocytes. No...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1989.tb07711.x
更新日期:1989-07-01 00:00:00
abstract::This retrospective analysis was conducted in 64 patients diagnosed with type I cryoglobulinaemia (CG) followed at two French centres. Median follow-up was 6·75 years. CG was IgG in 60% and IgM in 40% of all cases and was asymptomatic in 16 patients (25%). Cold-triggered ischaemic skin manifestations were observed in 3...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/bjh.13196
更新日期:2015-03-01 00:00:00
abstract::Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare, recessively inherited genetic disorder with varying clinical presentation that is caused by ADAMTS13 mutations. Several studies have found limited associations between ADAMTS13 mutations and cTTP phenotype. The use of in silico tools that examine multipl...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.12214
更新日期:2013-03-01 00:00:00
abstract::Multiple myeloma cell lines express functional receptors for insulin-like growth factors (IGFs) and several cell types that make up the bone marrow microenvironment produce these cytokines. This suggests that IGFs may play a role in survival and/or expansion of the malignant clone within the marrow in patients with mu...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.592708.x
更新日期:1997-05-01 00:00:00
abstract::The combination of bortezomib and rituximab was evaluated in patients with mantle cell lymphoma (MCL), follicular lymphoma (FL) and Waldenström macroglobulinaemia (WM), in a Phase I and later, a randomized Phase II study. In the randomized study, 42 patients with recurrent/refractory disease received either: bortezomi...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/j.1365-2141.2010.08340.x
更新日期:2010-11-01 00:00:00