摘要:

CD56 has been found to identify an isoform of the neural cell adhesion (NCAM). NCAM is a member of the immunoglobulin superfamily of cell adhesion molecules; it is related to a variety of leukocyte antigens and to several cell adhesion molecules believed relevant to malignant behavior in a variety of neoplasms. It contains poly sialic acid, which appears to regulate binding avidity of NCAM and other cell adhesion processes.We have identified a group of NCAM-positive lymphomas. Compared to a group of NCAM-negative lymphomas, this group exhibited frequent involvement of unusual sites and a generally aggressive course. Another series of CD56-positive hematolymphoid malignancies has recently been described, from Hong Kong; this group also exhibited involvement of unusual sites and displayed a very aggressive course. Together these series suggest that NCAM on lymphoma is of biological and clinical significance in terms of tumor behavior and spread.

ISSN:1042-8194    

DOI:10.3109/10428199309059565

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Conflicting results have been reported in recent years concerning the incidence and prognostic relevance of acute mixed-lineage leukemias (AMLL). Among the high number of possible hybrid antigen combinations, it is important to discriminate those occurring with sufficient frequency to be of general clinical significance. In this review an approach to a classification based upon the hierarchical import of developmental antigens seen during hemopoietic differentiation is suggested. As far as the clinical relevance of AMLL is concerned, some hybrid patterns have been found to be associated with distinct characteristics in terms of clinical features at the time of presentation and poor response to treatment. For these particular types of leukemia, the time has probably arrived to design more specific therapeutic regimens.

ISSN:1042-8194    

DOI:10.3109/10428199309059566

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

We recently characterized a novel putative intermediate-filament associated protein which is strongly expressed in the Reed-Sternberg cells of Hodgkin's disease. Therefore we named the protein‘restin’, an acronym forReed-Sternbergcell intermediate filament-associated protein. The protein is also expressed in anaplastic large cell lymphoma or Ki-1 lymphoma, a non-Hodgkin's lymphoma phenotypically related to Hodgkin's disease. Although the functions of restin are not yet fully elucidated, transfection experiments demonstrate that over-expression of the protein increases cell growth by a mechanism which may involve upregulation of the transferrin receptor. Hence, restin may contribute to neoplastic transformation in Hodgkin's disease and anaplastic large cell lymphoma. Study of the mechanisms leading to restin overexpression may provide important data on the etiology of Hodgkin's disease and its relation to anaplastic large cell lymphoma.

ISSN:1042-8194    

DOI:10.3109/10428199309059567

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Cytokines play an important role in the regulation of both normal and malignant B cells. In this paper we give a brief overview of the major cytokines involved in the regulation of B-CLL proliferation.In vitroexperiments have indicated that there is an antagonistic interaction between TNF-αas a growth-enhancing factor and IL-4, which inhibits the growth of B-CLL. We have extended these findings with recent experiments on the intracellular signals which might be involved in these processes. We show that increased levels of intracellular cAMP dose-dependently inhibit the TNF-α-induced proliferation of B-CLL. On the basis of these results, we propose a model for the signals involved in the regulation of B-CLL proliferation. The implications for possible new ways of treatment are discussed.

ISSN:1042-8194    

DOI:10.3109/10428199309059568

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The therapy for myelodysplastic syndromes (MDS) and acute leukemia (AL) transformed from MDS is not well established. Etoposide (VP 16-213) at low concentrations shows differentiation-inducing activity against leukemic cells in vitro. A prior study showed that oral low-dose etoposide therapy was effective in patients with chronic myelomonocytic leukemia. We used low-dose etoposide to treat six patients with refractory anemia with excess blasts in transformation (RAEB-t) and seven patients with AL transformed from MDS. The etoposide (50 mg, 2-7 times/week) was usually administered intravenously to ensure reliable bioavailability. Of 12 assessable patients, four RAEB-t patients achieved a partial response and one AL patient achieved complete remission. The responders became transfusion-independent, and this continued for 2-9 months while etoposide therapy was continued. Three of five responders had been resistant to prior repeated low-dose cytarabine therapy. The side effects were mild and well tolerated. Heterogeneous mechanisms were surmised to explain the clinical effects of low-dose etoposide. Several aspects, including the optimal schedule of low-dose etoposide therapy, the effect of this therapy on the patients' survival, the usefulness of combination therapy with other chemotherapeutic drug(s) and/or cytokine(s), should be investigated in the future.

ISSN:1042-8194    

DOI:10.3109/10428199309059569

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Herbimycin A, a benzoquinonoid anasamycin antibiotic, has been shown to reserve the oncogenic phenotypes of p60v-srctransformed cells by the virtue of the inhibition ofsrcprotein tyrosine kinase. Furthermore, we previously demonstrated that herbimycin A displayed the antitumor activity on Ph1-positive leukemia cells andbcr/abloncoprotein-associated transformed murine hematopoietic cells with the transfection of a retroviral vector expressingbcr/abl. Herbimycin A showed preferential inhibition on thein vitrogrowth of Ph1-positive leukemia cells andbcr/abloncoprotein-associated murine hematopoietic cells through the inhibition ofbcr/abltyrosine kinase activity and the reduction of subsequent phosphotyrosyl proteins. Recently, from the view of investigating the oncogenic significance or of developing a future clinical application in malignancies, several developing agents targeted against oncoprotein have been tried. We reviewed the present progress in the mechanism of oncoprotein-targeted antitumor effects and focused on herbimycin A-induced antitumor activity on Ph1-positive leukemia cells.

ISSN:1042-8194    

DOI:10.3109/10428199309059570

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The purpose of this trial was to evaluate the efficacy and the tolerance of high-dose therapy with autologous stem cell transplantation as part of front-line therapy in Hodgkin's disease for patients with both adverse prognostic factors: high tumor burden at presentation and slow response to initial chemotherapy.In a prospective one-center study, 20 consecutive patients with slow response (tumor reduction0.45 at T5-T6) (6 pts) or both stage IV + LMI (7 pts). Median time between diagnosis and autotransplantation was 5 months. Intensive therapy consisted of either CBV (cyclophosphamide 1.5 g/m2×4, BCNU 300 mg/m2, etoposide 200 mg/m2×3) (12 pts) or cyclophosphamide 120 mg/kg + 12 Gy total body irradiation for 8 patients with diffuse bone or lung involvement. For pts treated with CBV, 40 Gy involved field radiotherapy was performed after hematological recovery.Median duration of neutropenia was 16 days (9-21). Neither veno-occlusive disease, nor interstitial pneumonitis nor toxic death were observed. Seventeen pts are alive with no progression of the disease (16/16 in partial response after initial chemotherapy, 1/4 with refractory disease). Three pts with refractory disease before autotransplantation died from progressive disease. The actuarial EFS is 84.7% with a median follow-up of 23 months (8 to 52).We conclude that early intensive therapy with autotransplantation is well tolerated and effective, but given the results of conventional HD therapies, it has to be restricted for very selected patients.

ISSN:1042-8194    

DOI:10.3109/10428199309059571

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Chronic lymphocytic leukemia (CLL), despite an overall good prognosis, has a subgroup of patients with more rapid, aggressive disease. In an attempt to generate additional information about the B cell clones in B-CLL which could be used as predictive parameters, we analysed CD5 membrane phenotype and B cell colony growth in 29 B-CLL patients. CD5, a 67-kd glycoprotein, has been reported to be a consistent feature of the malignant B cell membrane phenotype in CLL. We used anin vitroB cell colony assay to study thein vitrogrowth, differentiation, and cell surface properties of CLL B cells. Finally, a variety of standard clinical parameters were collated for each patient. Monoclonal antibodies to both CD5 and CD 19 (pan B cell marker) were used to perform 2-color flow cytometry on freshly purified CLL B cells and on CLL B cells harvested after 7 days ofin vitroculture. We demonstrate here that CLL B cells are heterogeneous with respect to their expression of CD5, and that this expression is not fixed but may vary bothin vivoandin vitro. In vitrogrowth potential, as measured by the B cell colony assay, was also heterogeneous with three subgroups defined as low growth (85% CD5 positive) and lymphocyte doubling time less than 12 months and treatment within six months was detected. This study emphasizes that additional information regarding the biology of the malignant CLL B cell will generate new parameters that can be used to help predict the clinical course of B-CLL.

ISSN:1042-8194    

DOI:10.3109/10428199309059572

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

During the period January 1983 to January 1988 1597 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) were included in a Western Danish population-based NHL registry. Of these, 31% (N = 496) were low-grade NHL (LG-NHL) consisting of (Kiel): 9% lymphocytic (LY), 27% lymphoplasmacytic/-cytoid (IC), 53% follicular centroblastic/-centrocytic (CB/CCf) and 11% unclassifiable low-grade. LG-NHL (age range: 26-94 yrs, median: 64 yrs; M/F ratio: 0.8) had an age-standardised incidence rate (IR) of 2.7/105/yr. Age-specific IR's showed an age-related exponential rise in all subtypes except for CB/CCf. Compared with the intermediate (IG)- and high-grade (HG) group, LG-NHL had more female cases (M/F ratio: 0.79 vs. 1.2; p = 0.0002), a higher frequency of stage III-IV disease (66% vs. 53%; p<0.00005) and of bone marrow involvement (39% vs. 19%; p<0.00005). A later revision of all IC cases (N = 132) distinguished 79 non-polymorphic (ICnp) from 25 polymorphic (ICp) cases; 28 cases were differently classified. In 34 LG-NHL patients histologic transformation was verified: CB/CCf to CB diffuse (22 pts) and LY to immunoblastic or CB type (6 pts). The 7-yr survival for LG-NHL was 63% (IG: 48%, HG: 38%; p<0.00005). A Cox-regression analysis identified the following adverse prognostic factors for survival in LG-NHL: age≤50 with a relative risk (RR) of 3.2, hepatic involvement (RR = 2.1), elevated s-LDH (RR = 1.9), B-symptoms (RR = 1.8) and IC histology (ICnp + ICp) (RR = 1.7). ICp had a lower 7-yr survival than ICnp (p = 0.045). A univariate analysis performed on young LG-NHL patients (≤50 yrs), of which 79% of cases had a CB/CCf histology, identified hyperuricaemia, number of extranodal sites, hepatic involvement, elevated s-LDH, B-symptoms and splenic involvement as high risk factors.

ISSN:1042-8194    

DOI:10.3109/10428199309059573

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

We examined bone marrow specimens from 19 patients with malignant histiocytosis (MH) and/or malignant lymphoma (ML) with concurrent hemophagocytic syndrome (HS) who suffered from high fever, hepatosplenomegaly, liver dysfunction, profound cytopenia, and erythrophagocytosis. There was little lymph-node enlargement or no tumor formation. The neoplastic cells in 3 patients exhibited histiocytes/macrophages phenotype with positive reactions for fluoride-sensitive nonspecific esterase, lysozyme and CD68 (KP1). Twelve other patients showed a T-cell (CD3) phenotype, in which 5 patients expressed CD30 (BerH2) as well. B-cell characteristics with CD20 (L26), CIg.νλandγκwere manifest in 2 patients, but indeterminate markers were found in the 2 remaining patients. Eighteen patients showed an infiltration of large neoplastic cells mainly with noncohesive interstitial growth pattern, ranging from 1.7% to 74.2% of the nucleated cells in the bone marrow. A large number of histiocytes/macrophages and dendritic cells was diffusely observed in 15 patients. Severely decreased hematopoiesis in all three series of hematopoietic cells was found in 16 patients.Bone marrow infiltration by the neoplastic cells and numerous reactive cells with erythrophagocytosis appears be an important factor of profound cytopenia in patients of MH and/ or ML with HS. The infiltrating pattern of the neoplastic and reactive cells in the bone marrow of MH and/or ML with HS was different from that of other types of peripheral T-cell ML, B-cell ML in high grade malignancy, and Hodgkin's disease. Cell characteristics and lineage of the neoplastic cells in MH and/or ML with HS are also discussed in this study.

ISSN:1042-8194    

DOI:10.3109/10428199309059574

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor