bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative pharmacokinetic study of idarubicin and daunorubicin in leukemia patients
Authors: Robert J. , Rigal‐Huguet F. , Hurteloup P. 
Published: February 2007

AbstractWe have studied the pharmacokinetics of idarubicin and daunorubicin in a total of 16 leukemic patients treated with one of these drugs associated with aracytine. The AUCs obtained for unchanged drugs were proportional to the dose, and the dose‐independent pharmacokinetic parameters were very similar for the two drugs: total plasma clearance (39·0L/h/m2 for idarubicin versus 38·6 for daunorubicin), total volume of distribution (1756 versus 1725 L/m2) and elimination half‐life (42·7 versus 47·4 h). The only metabolites detected were the 13–dihydroderivative of each drug, idarubicinol or daunorubicinol. The elimination half‐life of idarubicinol was two times higher than that of daunorubicinol (80·7 versus 37·3 h) which provided an AUC ratio metabolite/parent drug higher for idarubicin than for daunorubicin. In view of the fact that idarubicinol is a much more active metabolite than daunorubicinol, this protracted half‐life metabolite can account for the reported higher activity of idarubicin as compared to daunorubicin.
Intensive chemotherapy for peripheral T‐cell lymphomas
Authors: Liang Raymond , Todd David , Chan T. K. , Chiu Edmond , Lie Albert , Ho Faith C. S. , Loke S. L. 
Published: February 2007

AbstractForty‐two patients with previously untreated peripheral T‐cell lymphomas (PTCL) were treated with an intensive chemotherapy protocol. Either the BACOP or the m‐BACOD regimen was used for induction. Patients achieving complete clinical remission after three courses were given intensive consolidation and maintenance chemotherapy similar to the L10/L17M protocol designed by the Memorial Sloan‐Kettering Group for acute lymphoblastic leukemia and lymphoblastic lymphoma. There were 27 (64 per cent) males and 15 (36 per cent) females. The median age was 54 years (mean 53, range 15 to 68). Seven of them (17 per cent) had stage I disease, four (10 per cent) stage II, seven (17 per cent) stage III and 24 (57 per cent) stage IV. Eighteen patients (43 per cent) had B symptoms and four (10 per cent) had bulky disease. According to the Working Formulation, the histology was diffuse mixed in 16 patients (38 per cent), diffuse large cell in 18 (43 per cent), diffuse immunoblastic in four (10 per cent) and unclassifiable in four (10 per cent). According to a modified Japanese Lymphoma Study Group's classification, the histology in 24 patients (57 per cent) was the pleomorphic type, in 13 (31 per cent) immunoblastic‐lymphadenopathy‐like (IBL‐like), and in five (12 per cent) unclassifiable. The overall complete remission rate was 67 per cent. Twenty‐five per cent of the complete responders relapsed and the DFS of the CR patients was 62 per cent at three years. The overall survival of all patients at three years was 52 per cent. Patients with stage I, II and III disease had significantly better CR rate (100 per cent versus 42 per cent, p = 0·001) and overall survival (82 per cent versus 35 per cent at three years, p = 0·01) than those with stage IV disease but the relapse reate and DFS of CR patients were similar. This study shows that the prognosis of patients with PTCL can be improved by intensive therapy.
Bone mineral density (BMD) in patients with lymphoma: The effects of chemotherapy, intermittent corticosteroids and premature menopause
Authors: Ratcliffe Marcia A. , Lanham Susan A. , Reid David M. , Dawson Audrey A. 
Published: February 2007

AbstractYoung women with a chemotherapy‐induced early menopause are theoretically at considerable risk of developing post‐menopausal osteoporosis with problems developing earlier and more severely. In this study bone mineral density (BMD) measurements were made, using a dual‐energy X‐ray absorptiometer (DXA), at the spine and hip of 50 young women who had been treated for lymphoma, 24 of whom were post‐menopausal and 78, healthy age‐matched controls. On analysis of the results, there was no significant difference between the control group and the 26 post‐treatment, pre‐menopausal patients, but the BMD levels were significantly lower than the controls in the post‐menopausal group particularly in 16 patients who had been menopausal greater than 18 months. The results confirm that these young women with treatment‐induced premature menopause are at considerable risk of developing osteoporotic problems. Early recognition of this is important so that preventative measures with hormone replacement therapy can be initiated where this is safely possible. The results also indicate that chemotherapy for lymphoma (cytotoxics and high dose intermittent steroids), are unlikely to contribute directly to the lowering of the BMD of these patients.
Expression of leukocyte adhesion molecules (ICAM‐1/LFA‐1) related to clinical behaviour in B cell lymphomas
Authors: Nozawa Yoshihiro , Yamaguchi Yoshiko , Tominaga Kunihiko , Hojo Hiroshi , Abe Masafumi , Wakasa Haruki 
Published: February 2007

AbstractWe investigated the expression of adhesion molecules of lymphocyte function‐associated antigen‐lα(LFA‐lα) and its ligand intercellular adhesion molecule‐1 (ICAM‐1) on 74 well‐characterized B cell lymphomas. The LFA‐1 was expressed on B cell lymphomas (21/74; 28 percent), but to a lesser degree than ICAM‐1 which was highly expressed (48/74 cases; 64 per cent).From the results of bone marrow examination of 39 cases with B cell lymphomas, 13 of 16 cases with a lack of ICAM‐1 molecule showed a higher incidence of marrow involvement, but nine of 23 cases with the expression of ICAM‐1 molecule showed a lower incidence.These findings suggest that the lack of expression of the ICAM‐1 molecule by B cell lymphomas correlates with bone marrow involvement by lymphoma cells (p < 0·05). Expression of the LFA‐1 molecule appears not to correlate with marrow involvement (p < 0·05).
Solitary plasmacytoma of bone: Clinical features, treatment and survival
Authors: Ellis P. A. , Colls B. M. 
Published: February 2007

AbstractEleven patients with solitary plasmacytoma of bone were seen between 1978 and 1991. A retrospective review of the clinical features, treatment and survival of these patients was made with the aim of helping to define those at risk for early development of myeloma. Nine patients (82 per cent) had paraparoteinemia at diagnosis. Treatment consisted of local irradiation plus or minus surgery (nine patients) and surgery alone (two patients). No patient received adjuvant chemotherapy. One patient had evidence of both generalized osteopenia and immunoparesis, and progressed to myeloma within six months. Four patients (36 per cent) progressed to myeloma. All of these had paraprotein levels which continued to rise following initial treatment. Three patients died of myeloma at 12, 81 and 144 months and the other patient is alive with myeloma at 6 months. Patients without paraproteinemia at presentation or whose paraprotein decreased after treatment did not progress to myeloma. Three patients have been followed for 8, 11 and 19 years with no evidence of myeloma. Failure of paraprotein to clear after local treatment suggests occult disseminated disease and is predictive of later development of overt myeloma.
Expression of p170 protein in multiple myeloma: A clinical study
Authors: Ucci Giovanni , Petrini Mario , Riccardi Alberto , Invernizzi Rosangela , Carulli Giovanni , Luoni Renata , Giordano Monica , Danova Marco 
Published: February 2007

AbstractThe expression of the p170 multidrug resistance protein by bone marrow plasma cells (BMPC) was assessed at clinical presentation in 53 patients with multiple myeloma (MM) using the C219 monoclonal antibody. Twenty‐two of the 53 (41 per cent) patients had variable aliquots (1–60 per cent, median = 6 per cent) of p170 + BMPC by immunocytochemistry. Five of 10 patients studied using bivariate flow cytometry had both diploid and hyperdiploid (DNA index ranged from 1·2 to 1·5) BMPC with hyperdiploid clones having significantly greater p170 expression than diploid ones. Of the 37 patients evaluated for a response, 20 (54 per cent) had responded to induction chemotherapy. The presence of p170+ BMPC was a negative indicator for achieving response. The response rate was 75 per cent for p170‐ and 25 per cent for p170 + cases (p< 0·01), with no difference on the basis of treatment schedule (melphalan and prednisone, 24 patients; peptichemio, vincristine and prednisone, 13 patients). No difference in response and survival duration was found between p170+ and p170‐ patients. In six of nine patients studied both at diagnosis and following induction chemotherapy the p170+ BMPC% increased irrespective of the type of treatment or outcome.
Verapamil preferentially potentiates in‐vitro cytotoxicity of vincristine on malignant lymphoid cells
Authors: Malik Imtiaz A. , Costea Nicolas V. 
Published: February 2007

AbstractVerapamil has been shown to overcome acquired drug resistance to vincristine in P388 leukemia both in vitro and in vivo. To study the selectivity of this action, the effect of addition of verapamil on the cytotoxicity of vincristine was studied using lymphocytes from eight patients with chronic lymphocytic leukemia (CLL). lymphoblasts from a T‐acute lymphoblastic leukemia (T‐ALL) cell line (GM 3639), and peripheral blood lymphocytes (PBL) from eight normal healthy volunteers. Using the differential staining cytotoxicity (DiSC) assay, we demonstrated that verapamil at 1 μm concentration potentiated the in‐vitro cytotoxicity of vincristine on CLL and GM 3639 cells in concentrations of 0·04–0·25 μg/l. There was however, no enhancement of cytotoxicity noted against the control PBL. The data demonstrate that verapamil preferentially enhances the in‐vitro cytotoxicity of vincristine on CLL and GM 3639 cells but no enhancement of cytotoxicity is seen against PBL.
Role of blast cell immunophenotyping for the diagnosis and prognosis of acute myeloid leukemia
Authors: Dubosc‐Marchenay Nadine , Lacombe Francis , Dumain Patrice , Marit Gerald , Montastruc Marion , Belloc Francis , Reiffers Josy 
Published: February 2007

AbstractBone marrow blast cell antigen expression from 86 patients with de novo acute myeloid leukemias (AML) was studied and correlated with FAB classification and clinical outcome. Among a panel of 14 monoclonal antibodies routinely used for the diagnosis of acute leukemias we studied the expression of six antibodies (CD13, CD15, VIM2, CD33, CD14, CD34) of the granulomonocytic lineage and found that some of them were useful for diagnosis and/or prognosis. For FAB subclassification of AML, the CD13 or VIM2 antigen expression was of no benefit. Monocytic leukemias (M4+M5PD+M5WD) more frequently expressed CD34 antigen (28/31) than granulocytic (M1+M2+M3) subtypes (33/53) (P<0·01). Finally, the most striking differences were found with CD14 antigen expression: CD14 antigen was more frequently expressed in M4+M5 leukemias (21/31) than in M1+M2+M3 subtypes (12/33) (P<0·01). The mean percentage of CD14 positive blast cells was accordingly higher in monocytic leukemias than in granulocytic leukemias and the difference was highly significant (P 0·0001). The CD15 antigen was more frequently expressed in differentiated leukemias (M2+M3+M4+M5WD) (35/44) than in poorly differentiated forms (M1+M5PD) (17/37) (P<0·001). The statistical difference was higher when the mean percentage of CD15 positive blast cells were compared (P<0·0003). Moreover these latter percentages were different in M1 and M2 subtypes (P<0·003). The blast cell expression of CD13, CD14, CD15 or CD33 was not predictive of the length of CR or survival. Moreover, our results support previously published findings suggesting a longer overall survival duration for patients whose leukemic cells do not express the CD34 antigen (P<0·01). We also confirm that patients with the more differentiated subtypes of AML (CD13‐, CD34+) tend to survive longer than patients with the less differentiated subtypes of AML (CD13–, CD34+) (P<0·001).
Protein kinase C isozyme expression in human leukemia–lymphoma cell lines—an immunocytochemical study
Authors: Hojo Hiroshi , Morimura Yutaka , Abe Masafumi , Tominaga Kunihiko , Nozawa Yoshihiro , Nakamura Naoya , Ono Nobutaka , Tasaki Kazuhiro , Yamaguchi Yoshiko , Suzuki Sayuri , Wakasa Haruki 
Published: February 2007

AbstractThere have been an increasing number of reports describing a pivotal role for phosphorylation in cellular responses for cell differentiation and proliferation. We examined an immunocytochemical expression of protein kinase C(PKC) isozymes (type I, II, and III) in 22 leukemia–lymphoma cell lines. Of these cell lines, 21 expressed type II PKC and 17 showed the co‐expression of both types II and III PKC in varying degree. The cell line without PKC activity showed far less [3H]‐TdR uptake and no heterotransplantation in nude mice.Types II and III PKC appear to relate to cell proliferation in certain leukemia–lymphoma cell lines.
Production of multiple cytokines by Hodgkin's disease derived cell lines
Authors: Klein S. , Jucker M. , Diehl V. , Tesch H. 
Published: February 2007

AbstractThe production of cytokines was analysed in Hodgkin's disease (HD) derived cell lines by enzyme linked immunosorbent tests (ELISA) and Northern blot experiments. Our results demonstrate that HD derived cell lines produce a variety of cytokines, such as ILlα, IL4, IL5, IL6, IL8, TNFα, TNFβ and GM‐CSF but not ILlβ IL2, IL3 and G‐CSF. In cell lines with a high expression of CD25 (the light chain of the IL2 receptor), we found soluble IL2 receptors in the supernatants. In addition, receptors for IL6 could be detected in most of the HD derived cell lines. However the growth of HD derived cell lines, which produce IL6 and IL6 receptors could not be inhibited by anti‐IL6 antibodies. From our data we conclude, that IL6 and additional cytokines may be involved in the biology of HD.
Protein phosphatase 2Aα involvement in granulocytic differentiation of HL‐60 cells
Authors: Sasaki Kazunori , Ikeda Kazuma , Nagai Masami , Shima Hiroshi , Nagao Minako , Takahara Jiro , Irino Shozo 
Published: February 2007

AbstractProtein phosphatase 2Aα (PP‐2Aα) is one of the catalytic subunits of PP‐2A, which is composed of catalytic and regulatory subunits. In fission yeasts, PP‐2A mutants cause mitotic defects and strikingly different cell cycle phenotypes. In rat hepatocellular carcinomas, mRNA expression of PP‐2Aα was increased compared to that of normal hepatocytes. From these studies, PP‐2Aα has been thought to be involved in proliferation, and we expected that PP‐2Aα would decrease in HL‐60 cells on dimethyl sulfoxide(DMSO)‐induced granulocytic differentiation with decreased growth rate. In this study, we show that PP‐2Aα expression increases in HL‐60 cells on DMSO‐induced granulocytic differentiation, while PP‐1γ, which is one of catalytic subunits of protein phosphatase 1, expression did not change significantly. These results suggest that PP‐2Aα may be involved in regulation of differentiation of hematopoietic cells.
Post‐transcriptional regulation of interferon‐alpha 4 subtype production by lymphoblastoid cells
Authors: Greenway Alison L. , Brandt Evelyn R. , Hertzog Paul J. , Devenish Rodney J. , Linnane Anthony W. 
Published: February 2007

AbstractThe constitutive production of interferon‐alpha (IFN‐α) subtypes by the lymphoblastoid cell lines. Namalwa, Daudi and Raji, was investigated using sensitive and semi‐quantitative flow cytometric techniques. Further, we sought to determine whether the previously described failure of these cell lines to produce IFN‐α‐4 was a result of the deletion of the IFN A4 gene. Cytoplasmic production of IFN‐α‐2 and IFN‐α‐4 was assessed using IFN‐α subtype‐specific antipeptide antibodies and FITC‐labelled secondary antibodies in indirect immunofluoresence‐flow cytometry studies. The constitutive production of IFN‐α‐2 was detected in all three cell lines. Significant increases in fluorescence representing increased production of IFN‐α‐2 and possibly other IFN‐α subtypes were detected after induction by Sendai virus. Approximately 100 per cent of cells in the Namalwa, Daudi and Raji cell populations contained IFN‐α‐2 before and after induction. However, no cells from the same cell populations contained the IFN‐α‐4 subtype. Analysis of genomic DNA isolated from the lymphoblastoid cells using the Polymerase Chain Reaction (PCR) and oligonucleotide primers specific for IFN A2 or IFN A4 confirmed the presence of the genes encoding both IFN‐α subtypes. Furthermore, using reverse transcriptase‐PCR amplification, mRNAs for both IFN‐α‐2 and IFN‐α‐4 were detected. Therefore, in contrast to some leukaemias and derived cell lines where IFN A genes have been deleted, these cell lines of B cell lineage exhibit selective expression of IFN A genes, as a result of altered transcriptional/translational control of IFN‐α expression.
The effect of cytokines on cultured mononuclear cells from patients with B cell chronic lymphocytic leukemia
Authors: Burke Frances , Griffin Dorota , Elwood Nagaire , Davis Carol , Stamp Gordon , Rohatiner Anna , Lister T. Andrew , Balkwill Frances 
Published: February 2007

AbstractIn the past 5 years a number of cytokines have been identified that control B cell development, proliferation, and maturation. The role of such cytokines in the evolution, pathophysiology, and treatment of B cell malignancies is an area of great interest. The in vitro response of freshly isolated peripheral blood mononuclear cells from patients with B cell chronic lymphocytic leukemia (B‐CLL) and a high white cell count, to four cytokines, IFN‐α, IFN‐γ, IL‐2 and TNF, was studied. No culture condition or cytokine resulted in a significant increase in cell number over 4 days, cells survived better in autologous serum than in heat inactivated foetal calf serum, and a small but significant increase in blast cells was seen when the cells were cultured in IL‐2. There was a discrepancy between uptake of thymidine and increase in cell number which can be explained by the low labelling index of these cultures and the fact that cells can incorporate [3H]‐thymidine without going into mitosis. The majority of cultures produced biologically active TNF at levels ranging from 1 to 40 pg/ml. In IFN‐α treated cultures TNF levels were decreased. Cultures contained biologically active IL‐6 at levels ranging from 2 to 2800 U/ml. IL‐6 production was not influenced by other cytokines. Thirteen of 28 patients had detectable IL‐6 in their serum, but in cells lysed no more than 2 h after removal from the patient, message for IL‐6 could not be detected by Northern blotting. Cells also failed to express IL‐1β mRNA but seven of eight patients had low levels of TNF message. Preliminary data using in situ hybridization techniques revealed that whilst no mRNA for IL‐6 was detected, TNF and IL‐1β mRNA were detected in a minoority of mononuclear cells.
Solid tumour with initial presentation in the bone marrow—a clinicopathologic study of 25 adult cases
Authors: Wong K. F. , Chan J. K. C. , Ma S. K. 
Published: February 2007

AbstractThis study reviews the clinicopathologic features of 25 adult patients without a known history of malignancy presenting with metastic carcinoma in the bone marrow. The disease mainly affected middle‐aged to elderly males (mean age, 61·6 years). Bone pain, generlized or confined to the back, was a common presenting complaint. Organomegaly was often absent. Laboratory abnormalities included anaemia, leukocytosis, thrombocytopenia and a leukoerythroblastic blood picture. Serum alkaline phosphatase level was raised in the majority of cases. In about one‐third of the cases, malignancy was not suspected clinically, and bone marrow aspiration was carried out because of incidental finding of abnormal blood counts. The marrow aspirate findings were characterized by numerous to sparse cohesive tumour clusters with nuclear moulding. Over two‐thirds of the patients had metastatic adenocarcinoma, and the lung was found to be the commonest site of primary disease. We conclude that since the marrow infiltration can be subtle, marrow smears should be carefully scrutinized for tumour cells in patients with leukoerythroblastic blood picture, in particular those with an elevated serum alkaline phosphatase level.
Copp chemotherapy for elderly patients with intermediate and high grade non‐Hodgkin's lymphoma
Authors: Liang Raymond , Todd David , Chan T. K. , Chiu Edmond , Lie Albert , Ho Faith 
Published: February 2007

AbstractOne hundred and forty‐one consecutive patients above and 231 below the age of 60 years with previously untreated intermediate or high grade non‐Hodgkin's lymphoma were included in this study. Patients above the age of 60 years were treated with the COPP chemotherapy regimen. The younger patients, at or below the age of 60, received a doxorubicin‐containing regimen (119 had CHOP, 65 had BACOP and 47 had m‐BACOD). For stage I patients, the clinical results were similar but for stage II, III or IV disease, those receiving COPP had significantly worse CR rate and survival than those who had a doxorubicin‐containing regimen. Multivariate analysis on patients receiving the COPP chemotherapy revealed that the independent prognostic variables significantly determining CR rate and survival included clinical stage (p =0·04) and serum lactate dehydrogenase level (p =0·001). Myelosuppression was the major toxicity following COPP chemotherapy in this group of patients. There were 10 (7 per cent) treatment‐related deaths. Compared to the reported results using doxorubicin‐containing regimens to treat elderly patients with aggressive NHL in the literature, the more aggressive treatment does not appear to improve significantly the clinical outcome of this group of patients and seems to produce treatment results very much similar to COPP. However, accurate comparison is difficult because of the variation in the patient characteristics. Further prospective controlled randomized trials will be necessary to determine the optimal therapy for these patients.
Subcutaneous low dose arabinosyl‐cytosine and oral idarubicin in high risk adult acute myelogenous leukemia
Authors: Kusnierz‐Glaz C. R. , Normann D. , Weinberg R. , Fuchs R. , Flasshove M. , Hiddemann W. , van de Loo J. , Büchner Th. 
Published: February 2007

AbstractIn order to further explore low dose chemotherapy for high risk acute myelogeneous leukemia (AML), low dose Ara‐C and oral idarubicin (LAI) were given to 33 patients of 24–84 (median 66) years with AML after myelodysplastic syndrome (MDS) (12 patients), refractory AML (13 patients), and AML with contraindications to intensive chemotherapy (8 patients). Patients received 1 to 4 cycles of Ara‐C 10 mg/m2 q 12 h s.c. inject. on days 1–14 and idarubicin 20 mg/m2/d orally days 3, 4, 5. Three patients attained complete remission, four patients partial remission and one patient minor response, whereas 11 patients succumbed to early mortality from hemorrhage (two patients) and/or infections (10 patients). Three of 13 patients with heavily pretreated refractory AML went into remission compared to 3/12 with AML after MDS and 1/8 with AML and contraindications against intensive treatment. Median duration of CR is 102 (70–488+) days. Thirty‐two of 33 patients developed grade 4 hematological toxicity requiring platelet transfusions. The non‐hematologic toxicity was acceptable. LAI provides a standardized therapeutic option especially for heavily pretreated patients with AML.