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  • 1
    ISSN: 1569-8041
    Keywords: cutaneous T-cell lymphoma ; mycosis fungoides ; pentostatin ; Sézary syndrome ; T-CLL ; T-zone lymphoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Within this phase II EORTC trial, we have investigated the safety and efficacy of pentostatin in lymphoid malignancies. We have previously reported the results in T- and B-cell prolymphocytic leukemia, B-cell chronic lymphocytic leukemia (B-CLL) and hairy cell leukemia. This report focuses on the outcome in T-cell malignancies: T-CLL, Sézary syndrome (Sézary), mycosis fungoides (MF) and T-zone lymphoma (TZL). Patients and methods: Of the 92 patients with these diagnoses enrolled, 76 were evaluable for response and toxicity, i.e., 25 of 28 with T-CLL, 21 of 26 with Sézary, 22 of 26 with MF, and 8 of 12 with TZL. All patients had progressive and advanced disease. Pentostatin was administered at a dosage of 4 mg/m2 every week for the first 3 weeks, then 4 mg/m2 every 14 days for another 6 weeks, followed by maintenance therapy of 4 mg/m2 monthly for a maximum of 6 months. Results: Response rates (complete and partial responses) in patients with Sézary (n = 22) or MF (n = 21) were 33% and 23%, respectively, and in patients with T-CLL (n = 21) or TZL (n = 8) 8% and 25%, respectively. Sixteen (21%) patients died during the first ten weeks of treatment: twelve of progressive disease, two of infectious complications with progressive disease, one of myocard infarction and one of renal failure related to administration of i.v. contrast. Major toxicity (grade 3–4) included infection in 11% of patients, nausea/vomiting in 4%, diarrhea in 3%. Hematologic toxicity was mild to non-existent. Conclusions: We conclude that pentostatin is active in Sézary and MF but showed marginal activity in T-CLL or TZL. Toxicities are mild to moderate at the dose schedule administered. Due to its relatively specific lympholytic effect and its favorable toxicity spectrum, pentostatin might be especially useful for the palliative treatment of T-cell malignancies.
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  • 2
    ISSN: 1569-8041
    Keywords: 11q22–q23 deletion ; ataxia-telangiectasia ; ATM ; mantle-cell lymphoma ; tumor suppressor gene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Mantle-cell lymphoma (MCL) is geneticallycharacterized by the translocation t(11;14)(q13;q32) leading to anoverexpression of cyclin-D1, but additional chromosomal abnormalities appearto be required for MCL pathogenesis. Patients and methods:Deletions involving chromosome 11q, whichwere recently found as recurrent aberrations in MCL, were analyzed at themolecular level in a series of 81 MCL by fluorescence in situhybridization (FISH) with probes from a contiguous set of yeastartificial chromosomes (YACs) spanning bands 11q14–q24. Results and conclusions:Loss of chromosome 11 material wasobserved in 37 of the 81 MCL cases (46%). The consensus deletioncomprised YAC 801e11 containing the ATMgene. The minimal region ofloss was further narrowed with P1–derived artificial chromosome (PAC) probes.This allowed the identification of a deletion confined to the genomic regionof ATM, which, together with intragenic mutations found in the codingsequence, suggests a role of ATMas a tumor suppressor gene in MCL.
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  • 3
    ISSN: 1432-1440
    Keywords: T-cell lymphoma ; Osteosclerosis ; Lymphokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A patient with peripheral T-cell Lymphoma and aquired, systemic osteosclerosis is described. Bone histology showed a spectacular activation of osteoblasts accompanyed by massive new bone formation. Alkaline phosphatase in serum was elevated and increased to >2000 U/l when the lymphoma became refractory to chemotherapy. In the patient's serum an osteoblast-activating factor could be demonstrated using a rat osteogenic osteosarcoma cell line (ROS 17/2.8). The factor was absent during remission of the tumor. We conclude that osteosclerosis was a paraneoplastic syndrome in this patient due to the secretion of an osteoblast-stimulating factor by the T-cell lymphoma. This situation is similar to the secretion of osteoclast-activating factors described in B-cell lymphomas, particularly multiple myeloma. The characterization of such a factor could be of therapeutic relevance.
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  • 4
    ISSN: 1432-1440
    Keywords: Histological examination of bone marrow ; Staging non-Hodgkin's lymphoma ; Analysis of gene rearrangements ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The histological examination of bone marrow specimens is one of the standard procedures in staging non-Hodgkin's lymphoma. To investigate the validity of a conventional unilateral iliac crest biopsy, we performed a prospective study comparing histological findings with analysis of gene rearrangements in bone marrow samples and magnetic resonance imaging of bone marrow. Twenty-seven consecutive patients with non-Hodgkin's lymphoma (ten with high grade, seventeen with low grade) were studied. In twelve patients, histological examination revealed bone marrow infiltration. Results of histology and magnetic resonance imaging were discordant in three of the twenty-seven patients. With magnetic resonance imaging, suspected infiltration was found in two patients without histological evidence for bone marrow involvement in the disease. In one patient, an infiltration was described by histology but MRI revealed no pathological findings. In this case, DNA analysis confirmed bone marrow infiltration by detection of a clonal rearrangement of the immunoglobulin heavy chain gene. Analysis of gene rearrangements was performed in ten patients. As examined by histology, five of them had bone marrow involvement in the disease and five had not. In all these cases, analysis of gene rearrangements confirmed the histological findings. Our data show that, despite the small volume of bone marrow specimens, the sensitivity of an iliac lymphoma.
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  • 5
    ISSN: 1432-1440
    Keywords: Key words B-cell chronic lymphocytic leukemia ; Fluorescence in situ hybridization ; TP53 ; 11q22-q23 ; Comparative genomic hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In B-cell chronic lymphocytic leukemia (B-CLL) clonal chromosome aberrations are detected in approximately 40–50% of tumors when using conventional chromosome banding analysis. Most studies find trisomy 12 to be the most frequent chromosome aberration, followed by structural aberrations of the long arm of chromosomes 13 and 14. Trisomy 12 and the ”14q+” marker are associated with shorter survival times, while the patients with 13q abnormalities have a favorable outcome, similar to those with a normal karyotype. The development of molecular cytogenetic techniques has greatly improved our ability to detect chromosome aberrations in tumor cells. Using fluorescence in situ hybridization, chromosome aberrations can be detected not only in dividing cells but also in interphase nuclei, an approach referred to as interphase cytogenetics. The prevalence of specific aberrations in B-CLL is currently being reassessed by interphase cytogenetics. By far the most frequent abnormality are deletions involving chromosome band 13q14, followed by deletions of the genomic region 11q22.3-q23.1, trisomy 12, deletions of 6q21-q23, and deletions/mutations of the TP53 tumor suppressor gene at 17p13. The evaluation of the true incidence of these aberrations now provides the basis for more accurate correlations with clinical characteristics and outcome. Deletions/mutations of the TP53 gene have been shown to be associated with resistance to treatment and to be an independent marker for poor survival. 11q deletions have been associated with extensive nodal involvement, rapid disease progression, and short survival times. Whether trisomy 12, 13q14, and 6q deletions have a prognostic impact awaits further study. The application of these molecular cytogenetic techniques will also contribute to the identification of the pathogenetically relevant genes that are affected by the chromosome aberrations in B-CLL.
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  • 6
    ISSN: 1432-2307
    Keywords: Key words Clinical course ; Immunohistochemistry ; Morphology ; Primary gastric T-cell lymphoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In contrast to primary gastric lymphomas of B-cell type, little is known about primary gastric T-cell lymphomas. We describe three cases with remarkably similar features: diffuse growth, epitheliotropism, medium too large cell size, high apoptotic rates, and a CD3+, CD4+, CD8+, CD45RO+ immunophenotype. Clonal TCRγ gene rearrangement was shown in two cases. Epstein-Barr virus infection was excluded in two cases. Taking advantage of fresh-frozen material, we analyzed two cases further, revealing CD5–, CD16+, CD56–, CD57–, CD25+, CD30+, CD103 (αEβ7)+, bcl-2 protein+, CD95+, CD95 ligand(L)–. CD95L, however, was detected in histiocytic and fibroblastoid by stander cells. The lymphomas expressed granzyme B, perforin, and the TIA-1 antigen in various combinations. All three cases had a very unfavorable clinical course characterized by local recurrence and/or dissemination to other epithelial sites, leading to death within 6–12 months after the initial diagnosis despite surgery and aggressive antineoplastic treatment. These data suggest a novel variant of peripheral T-cell lymphoma operationally characterized as primary gastric, apoptosis-rich, CD103+, EBV-, T-cell lymphoma co-expressing CD4, CD8, CD16 and cytotoxic molecules.
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  • 7
    ISSN: 1432-0584
    Keywords: Key words B-CLL ; FISH ; Chromosome abnormalities ; TP53 ; 11q22-q23 ; Prognostic factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The genetic alterations underlying the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) are difficult to assess. Cytogenetic studies are hindered by the low in vitro mitotic activity of the tumor cells and the limited resolution of chromosome banding. Molecular genetic analyses are hampered by nonclonal cells contained in the specimens and by the limited knowledge of candidate genes involved. As a complement to cytogenetic and molecular genetic techniques, fluorescence in situ hybridization (FISH) has proven powerful in the molecular cytogenetic analysis of B-CLL. FISH allows the detection of aberrations such as trisomies, deletions, and translocation breakpoints on the single cell level in dividing as well as nondividing cells without the prerequisite of detailed physical maps or knowledge of involved genes. As detected by the interphase cytogenetic FISH approach, the most common chromosome abnormalities of B-CLL are deletions in band 13q14, followed by deletions in 11q22-q23, trisomy 12, deletions in 17p13, and deletions in 6q21. Abnormalities in 17p13 seem to involve the TP53 tumor suppressor gene, but as yet no candidate genes have been identified for the other frequent aberrations. Toward the identification of such genes by positional cloning, FISH can be applied for detailed aberration mapping at the molecular level. Furthermore, the accurate detection of chromosome aberrations in B-CLL by FISH provides a valid basis for the evaluation of their prognostic significance. Inactivation of TP53 in 17p13 and deletions in 11q22-q23 have already been shown to be among the most important independent prognostic factors. Genetic abnormalities may eventually provide biological parameters, allowing a risk assessment for individual patients at the time of diagnosis of this clinically heterogeneous disease.
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  • 8
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Comparative genomic hybridization (CGH) has been used for a genome-wide screening of genetic imbalances in tumours. As CGH to chromosomes is technically difficult and yields only limited resolution, the chromosome targets were replaced by arrays of defined DNA fragments, an approach termed ...
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  • 9
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Combining data obtained by gene expression profiling with other sample-related data (for example clinical data in the case of patient samples) should increase the amount of information that can be extracted from the raw data. We performed a feasibility study by systematically comparing large-scale ...
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  • 10
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