In the 1970s Hawthorne reported an electrochemical dehydrocoupling reaction of the -carborane anion [HCBH] to form the biscarborane [CBH] . In this Communication we show that the said "Hawthorne Reaction" can be achieved thermally and that it tolerates C-butylation. The new compound was fully characterized by B, H, and C NMR spectroscopies, high-resolution mass spectrometry, and single-crystal X-ray diffraction.
View Article and Find Full Text PDFAims: To reassess the prognostic validity of immunohistochemical markers and algorithms identified in the CHOP era in immunochemotherapy-treated diffuse large B cell lymphoma patients.
Methods And Results: The prognostic significance of immunohistochemical markers (CD10, Bcl-6, Bcl-2, MUM1, Ki-67, CD5, GCET1, FoxP1, LMO2) and algorithms (Hans, Hans*, Muris, Choi, Choi*, Nyman, Visco-Young, Tally) was assessed using clinical diagnostic blocks taken from an unselected, population-based cohort of 190 patients treated with R-CHOP. Dichotomizing expression, low CD10 (<10%), low LMO2 (<70%) or high Bcl-2 (≥80%) predicted shorter overall survival (OS; P = 0.
Tissue biopsy specimens in the form of formalin-fixed paraffin-embedded tissue (FFPET) represent a valuable resource for biomarker identification and validation. However, to date, they remain an underused asset due to uncertainty regarding RNA extraction and the reliability of downstream techniques, including quantitative RT-PCR. Recently, much interest has emerged in the study of microRNAs; small single-stranded RNAs with a role in transcriptional regulation, that are thought to be well preserved in FFPET.
View Article and Find Full Text PDFA paradigm of cytokinesis in animal cells is that the actomyosin contractile ring provides the primary force to divide the cell. In the fission yeast Schizosaccharomyces pombe, cytokinesis also involves a conserved cytokinetic ring, which has been generally assumed to provide the force for cleavage (see also [5]). However, in contrast to animal cells, cytokinesis in yeast cells also requires the assembly of a cell wall septum, which grows centripetally inward as the ring closes.
View Article and Find Full Text PDFThe SHIELD program for Hodgkin lymphoma in patients 60 years of age or older, prospectively evaluated clinical features and outcome in a large patient cohort (n = 175). The central element was a phase 2 study of VEPEMB chemotherapy (n = 103, median age 73 years) incorporating comorbidity assessment. A total of 72 other patients were treated off-study but registered prospectively and treated concurrently with: ABVD (n = 35); CLVPP (n = 19), or other (n = 18).
View Article and Find Full Text PDFPurpose: 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.
View Article and Find Full Text PDFThe report describes the feasibility of the addition of multiple viable HLA-mismatched unrelated cord blood units, to a low cell number matched unrelated cord, to assist clinical engraftment. An ablative stem cell transplant was performed in an adult with relapsed acute lymphoblastic leukaemia (ALL), using a single HLA-matched cord blood unit (mononuclear cell dose 0.8 × 10(7)), supported by six mismatched cord blood units (one unit per 10 kg recipient weight).
View Article and Find Full Text PDFThe microRNAs are endogenous, non-coding RNAs that play key roles in a range of pathophysiological processes by up- or down-regulating gene expression. Recent studies have shown that some microRNAs have oncogenic or tumour suppressor activity. Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin's lymphoma with a heterogeneous biology, which has impeded the clinical assessment of patients.
View Article and Find Full Text PDFEnteropathy associated T-cell lymphoma (EATL) is a rare type of peripheral T-cell lymphoma. At present, there are no standardized diagnostic or treatment protocols for EATL. We describe EATL in a population-based setting and evaluate a new treatment with aggressive chemotherapy and autologous stem cell transplantation (ASCT).
View Article and Find Full Text PDFChromosomal abnormalities are increasingly used to risk stratify adults with acute lymphoblastic leukemia. Published data describing the age-specific incidence of chromosomal abnormalities and their prognostic relevance are largely derived from clinical trials. Trials frequently have age restrictions and low recruitment rates.
View Article and Find Full Text PDFDiffuse large B-cell lymphoma (DLBCL) forms a heterogeneous collection of aggressive non-Hodgkin's Lymphoma in which three principle classes of neoplasia have been defined according to gene expression and immunophenotyping studies. The present investigation sought to examine the immunophenotype of proposed subgroups and relate these to patient survival. A series of 155 DLBCL treated uniformly with anthracycline therapy in clinical trials, were stratified upon the basis of common biomarker expression with combination immunophenotype being related to patient overall survival.
View Article and Find Full Text PDFAim: We aimed to describe and contrast the epidemiology of haematological malignancies among 0-14 and 15-24-year-olds in northern England from 1990 to 2002 and compare clinical trial entry by age group.
Patients And Methods: Incidence rates were examined by age, sex and period of diagnosis and differences were tested using Poisson regression. Differences and trends in survival were assessed using Cox regression.
CD31 is the physiological ligand for CD38. CD38 expression in a high percentage of malignant cells is a risk factor for patients with B-cell chronic lymphocytic leukaemia (B-CLL). A previous investigation demonstrated that quantification of CD38 improves upon the prognostic value of the percentage expression.
View Article and Find Full Text PDFAnti-apoptotic factors including IAP-survivin and bcl-2 are involved in carcinogenesis and predict for disease outcome for patients with cancer. We used RT-PCR and specific primers to generate two recombinant IAP-survivin proteins; one encoding for the full-length protein and the second comprising the survivin sequence incorporating amino acids 98 to 142. Both proteins were used to immunize mice and as capture antigens to screen NS1/immune splenocyte hybridoma supernatants for anti-survivin antibody in ELISA assays.
View Article and Find Full Text PDFThere is little information to date regarding the role of angiogenesis in Hodgkin lymphoma (HL). The present study examines micro-vessel density and the expression of vascular endothelial growth factor (VEGF) and platelet-derived endothelial growth factor (PdEGF) in lymph node biopsies of patients with HL at presentation and relapse. Using immunohistochemistry, the degree of new blood vessel formation and the expression of VEGF and PdEGF was assessed in Hodgkin-rich tissue.
View Article and Find Full Text PDFPurpose: To estimate the cost-effectiveness from a French payer perspective of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) alone compared with CHOP plus rituximab (R-CHOP) for treatment of patients with diffuse large B-cell lymphoma.
Methods: Mean patient survival, days of hospitalization, and chemotherapy costs during treatment were estimated from a Phase III trial in France, Belgium, and Switzerland. Survival during the trial was estimated using the Kaplan-Meier method; survival beyond the trial period was projected based on mortality rates from the Scottish and Newcastle Lymphoma Group database.
Utilising the Scotland and Newcastle Lymphoma Group population data for Hodgkin's disease (HD), collected over a 20-year period, it is evident that 20% of patients are over the age of 60 yr at diagnosis. Data from 674 patients are available. This group comprised 346 men and 328 women.
View Article and Find Full Text PDFWe have previously shown that quantification of CD38 expression using microbeads of specific antibody binding capacity (ABC) improves the prognostic value of CD38 expression in B-cell chronic lymphocytic leukemia, particularly for Binet Stage A patients. Quantification of CD38 expression using beads is expensive, time consuming and could be difficult to implement in a routine clinical laboratory. The calculation of relative median fluorescence (RMF) using the median fluorescence intensities of the test and control samples, is even more simply and cheaply obtained by flow cytometry and could be used as an alternative way of quantifying antigen expression.
View Article and Find Full Text PDFWe have examined in a population-based observational study the survival of young patients (less than 40 years) with follicular lymphoma (FL) treated conventionally and followed for up to 17 years (minimum 10, median 13 years). Data were derived from the Scotland and Newcastle Lymphoma Group (SNLG) database from 1986. Histology of all available cases was reviewed to ensure that patients met the modern criteria for diagnosis of FL.
View Article and Find Full Text PDFA large number of prognostic factors are available to help predict the outcome of patients who present with B-cell chronic lymphocytic leukemia (B-CLL). These include clinical stage, leukemic cell morphology, lymphocyte doubling time, the pattern of infiltration in bone marrow trephine biopsies, cytogenetic abnormalities, p53 function and serum factors such as beta-2 microglobulin. Two recently described major prognostic factors are immunoglobulin heavy chain variable region (IgVH) mutation status and cell membrane expression of CD38.
View Article and Find Full Text PDFThe prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992.
View Article and Find Full Text PDFHigh dose chlorambucil has been shown to be an effective single-agent treatment in chronic lymphocytic leukemia (CLL), and to be useful as part of combination chemotherapy in low-grade non-Hodgkin's (NHL) and Hodgkin's disease (HD). In general, it is well tolerated and can be used in an outpatient setting. The optimum dose of chlorambucil has not been defined and there are numerous different dosing schedules available.
View Article and Find Full Text PDFBackground: A single nucleotide polymorphism in the tumor necrosis factor type II receptor (TNFRII) gene, codon 196, results in the substitution of arginine (R allele) for methionine (M allele). The 196R allele is reportedly associated with an increased susceptibility to autoimmune disease, and donor 196R allele carriage correlates with increased severity of acute graft-versus-host disease (GVHD) after matched unrelated bone marrow transplantation (BMT).
Methods: We investigated the impact of donor and recipient TNFRII genotype on GVHD incidence and severity among 104 adult recipients of myeloablative sibling BMTs.