Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
1.
Br J Haematol ; 146(1): 34-43, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19388933

ABSTRACT

The effect of CMC-544, a calicheamicin-conjugated anti-CD22 monoclonal antibody, was analysed in relation to CD22 and P-glycoprotein (P-gp) in B-cell chronic lymphocytic leukaemia (CLL) and non-Hodgkin lymphoma (NHL) in vitro. The cell lines used were CD22-positive parental Daudi and Raji, and their P-gp positive sublines, Daudi/MDR and Raji/MDR. Cells obtained from 19 patients with B-cell CLL or NHL were also used. The effect of CMC-544 was analysed by viable cell count, morphology, annexin-V staining, and cell cycle distribution. A dose-dependent, selective cytotoxic effect of CMC-544 was observed in cell lines that expressed CD22. CMC-544 was not effective on Daudi/MDR and Raji/MDR cells compared with their parental cells. The MDR modifiers, PSC833 and MS209, restored the cytotoxic effect of CMC-544 in P-gp-expressing sublines. In clinical samples, the cytotoxic effect of CMC-544 was inversely related to the amount of P-gp (P = 0.003), and to intracellular rhodamine-123 accumulation (P < 0.001). On the other hand, the effect positively correlated with the amount of CD22 (P = 0.010). The effect of CMC-544 depends on the levels of CD22 and P-gp. Our findings will help to predict the clinical effectiveness of this drug on these B-cell malignancies, suggesting a beneficial effect with combined use of CMC-544 and MDR modifiers.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , ATP Binding Cassette Transporter, Subfamily B, Member 1/analysis , ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Antibodies, Monoclonal, Humanized , Cell Count , Cell Line, Transformed , Cell Line, Tumor , Cyclosporins/therapeutic use , Dose-Response Relationship, Drug , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm , Flow Cytometry , Humans , Immunosuppressive Agents/therapeutic use , Inotuzumab Ozogamicin , Jurkat Cells , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Lymphoma, Non-Hodgkin/immunology , Lymphoma, Non-Hodgkin/metabolism , Quinolines/therapeutic use , Sialic Acid Binding Ig-like Lectin 2/analysis , Sialic Acid Binding Ig-like Lectin 2/immunology , Treatment Outcome , Tumor Cells, Cultured
2.
Eur J Haematol ; 77(1): 14-8, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16827882

ABSTRACT

There have been few reports about the CD33 expression on multiple myeloma (MM) cells so far, showing that only a few patients expressed CD33 homogenously on their MM cells. However, in these reports, neither detailed clinical information nor its prognostic significance was described. Therefore, we analyzed the CD33 expression on MM cells from 63 newly diagnosed patients by flow cytometry and the correlation with other clinical parameters to determine the clinicopathological significance of this molecule. Fourteen (22%) patients were positive for CD33. Of the 14 patients with CD33+ MM, >80% of MM cells were positive in six (9.5%). The CD33+ patients had higher beta 2 microglobulin and lactate dehydrogenase levels and higher incidence of anemia and thrombocytopenia than did CD33- patients. The estimated 3-yr overall survival in CD33+ patients was significantly lower than in the CD33- ones (31% and 50%, respectively, P = 0.042). Especially, mortality within a year from diagnosis in the CD33+patients was higher than that in CD33- patients (43% and 10%, respectively, P = 0.005). Serial evaluation of CD33 expression showed that the amount of CD33 significantly increased after a variety of treatment including melphalan and steroid in individual patients. These results suggest that the CD33 expression might be associated with drug resistance to these conventional agents, and CD33 might be a useful target for the development of new therapeutic agents in MM.


Subject(s)
Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Multiple Myeloma/pathology , Adult , Aged , Aged, 80 and over , Anemia/etiology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Bone Marrow Examination , Drug Resistance , Female , Flow Cytometry , Humans , Male , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/mortality , Prognosis , Sialic Acid Binding Ig-like Lectin 3 , Survival Rate , Thrombocytopenia/etiology
3.
Int J Hematol ; 83(4): 318-23, 2006 May.
Article in English | MEDLINE | ID: mdl-16757431

ABSTRACT

We describe 2 patients with acute promyelocytic leukemia (APL) in whom torsade de pointes (TdP) developed during treatment with arsenic trioxide. Patient 1 was a 23-year-old woman with second-relapse APL. Ventricular premature beat bigeminy developed on day 27 of treatment, and episodes of TdP developed on day 28. Patient 2 was a 51-year-old woman with second-relapse APL who had cardiomyopathy due to prior anthracycline treatment. TdP developed on day 17 of treatment. Arsenic trioxide is known to cause electrocardiographic abnormalities, such as ventricular tachycardia and prolongation of QT interval. Patient 1 was given fluconazole as a concomitant drug. Patient 2 had cardiomyopathy and hypokalemia. Careful management is needed during arsenic trioxide therapy because this treatment prolongs the QT interval, possibly inducing episodes of TdP.


Subject(s)
Antineoplastic Agents/adverse effects , Arsenicals/adverse effects , Leukemia, Promyelocytic, Acute/complications , Oxides/adverse effects , Torsades de Pointes/chemically induced , Adult , Anthracyclines/administration & dosage , Anthracyclines/adverse effects , Antifungal Agents/administration & dosage , Antineoplastic Agents/administration & dosage , Arsenic Trioxide , Arsenicals/administration & dosage , Cardiomyopathies/chemically induced , Cardiomyopathies/complications , Female , Fluconazole/administration & dosage , Humans , Hypokalemia/chemically induced , Hypokalemia/complications , Leukemia, Promyelocytic, Acute/drug therapy , Middle Aged , Oxides/administration & dosage , Time Factors , Torsades de Pointes/drug therapy
4.
Leuk Lymphoma ; 45(9): 1803-8, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15223639

ABSTRACT

Prognostic assessment is crucial for the management of AML. Although the use of karyotype analysis for risk-stratification is widely accepted, prognosis of AML remains ambiguous, particularly for patients categorized into the intermediate cytogenetic risk group and additional markers are required for an accurate prediction of outcome. For this study, we used multiplex real-time RT-PCR, which can simultaneously quantify WT1 and 10 distinct fusion gene transcripts, to prospectively evaluate the pre-treatment bone marrow findings of 53 de novo AML patients. Five patients with normal karyotype or insufficient metaphases detected by conventional karyotype analysis proved to have AML1-MTG8, CBFbeta-MYH11 or PML-RARalpha fusion transcripts. WT1 overexpression was observed in 92% of the patients, and the levels were significantly higher in the cytogenetic favorable risk group, especially patients with PML-RARalpha. WT1 levels also correlated with the percentage of blasts in bone marrow, especially in cases of core-binding factor leukemia. There was no association between initial WT1 levels and outcome in terms of event-free survival or overall survival. These results suggest that multiplex real-time RT-PCR is rapid and useful for the precise cytogenetic stratification of AML, and that WT1 levels at presentation correlate with several biologic features of leukemia, but have no prognostic significance.


Subject(s)
Leukemia, Monocytic, Acute/diagnosis , Leukemia, Monocytic, Acute/genetics , Recombinant Fusion Proteins/genetics , Reverse Transcriptase Polymerase Chain Reaction , Transcription, Genetic/genetics , WT1 Proteins/genetics , Adolescent , Adult , Aged , Bone Marrow/metabolism , Female , Humans , Male , Middle Aged , Prospective Studies , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Neoplasm/genetics , RNA, Neoplasm/metabolism , Survival Rate , Treatment Outcome
5.
Mol Cancer Ther ; 1(12): 1035-42, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12481426

ABSTRACT

To identify genes involved in the sensitivity of acute myeloid leukemia (AML) cells to chemotherapy, we monitored gene-expression profiles of cancer cells from 76 AML patients using a cDNA microarray consisting of 23,040 genes. We identified 63 genes that were commonly overexpressed and 372 genes suppressed in AML. Because these genes represent key molecules for disclosing the molecular mechanisms of AML, they may be potential targets for drug development. We also found 28 that revealed different expression levels between good and poor responders to chemotherapy and appeared to be associated with chemosensitivity. On that basis, we developed a "Drug Response Scoring" system that was correlated well with individual sensitivity to an anticancer drug regimen. Among the 44 cases with positive drug-response scores by our definition, 40 achieved complete remission after treatment, whereas the only 3 of the 20 cases with negative scores responded well to the treatment. An ability to predict chemosensitivity should eventually lead to achievement of our goal of "personalized therapy."


Subject(s)
Genome , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/metabolism , Oligonucleotide Array Sequence Analysis , Adult , Aged , DNA, Complementary/metabolism , Down-Regulation , Female , Humans , Leukemia, Myeloid, Acute/genetics , Male , Middle Aged , RNA/metabolism , Up-Regulation
6.
Rinsho Byori ; 50(5): 519-23, 2002 May.
Article in Japanese | MEDLINE | ID: mdl-12078052

ABSTRACT

With a novel supersensitive reagent, we evaluated the utility of measuring plasma endotoxin level for the rapid and sensitive diagnosis of gram-negative bacteremia. Subjects were 112 febrile(more than 38 degrees C) patients suspected of having bacterial infection and 170 samples were collected. Venous blood was obtained aseptically before administering antibiotics. Blood culture and endotoxin assays were performed simultaneously with these materials. Plasma endotoxin levels were positive in 64 samples when the cut off index was postulated at 0.35 pg/ml, while only 5 samples when the cut off index was postulated at 5 pg/ml. When the cut off index was at 0.35 pg/ml, sensitivity was 86%, while it was 14% when the cut off index was 5 pg/ml. Gram-negative rods(GNR) were detected by blood culture in 14 cases and the average period to detect GNR was 14.8 hours. The presence of circulating viable bacteria is diagnosed by blood culture, but because of the serious consequence of bacterial sepsis, treatment is initiated even in the absence of an identifiable organism. Since plasma endotoxin level can be assayed in about 2 hours, it will be more practical if we adjust the cut off index according to the clinical situation.


Subject(s)
Endotoxemia/diagnosis , Endotoxins/blood , Gram-Negative Bacterial Infections/diagnosis , Reagent Kits, Diagnostic/standards , Adolescent , Adult , Aged , Aged, 80 and over , Evaluation Studies as Topic , Female , Gram-Negative Bacteria/isolation & purification , Humans , Leukemia, Myeloid, Acute/complications , Male , Middle Aged , Myelodysplastic Syndromes/complications , Sensitivity and Specificity
SELECTION OF CITATIONS
SEARCH DETAIL
...