Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of study was cochlear function estimation by means otoacoustic emission in children treated by leukaemia cytostatic drugs in course of the bone marrow proliferative diseases. The children after treatment of acute lymphoblastic leukemia or nongranulomatic malignant lymphoma according to BFM programme were examined in this study. Audiologic examination of children included tonal audiometry, tympanometry and otoacoustic emission as well. The results were compared to the findings of control group consisted of healthy children have never suffered from ear diseases and have never used ototoxic drugs. No significant differences in tonal audiometry and TEOAE were observed. Aggressive treatment of leukaemia does not result in hearing loss.
 ...
PMID:[Evaluation of cochlear function by means of otoacoustic emission in children treated with cytostatic drugs in the course of bone marrow proliferative diseases]. 1126 90

Blastic natural killer (NK)-cell leukemia/lymphoma is a neoplasm of NK origin with aggressive behavior. The disease affects mainly elderly people and often presents with skin lesions and overt leukemia. Blastic morphology, an NK-cell immunophenotype, and lack of association with Epstein-Barr virus are the clues for the diagnosis. We report herein, the case of a patient with a blastic NK-cell leukemia/lymphoma with overt leukemia at diagnosis, who achieved a complete response after CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy. However, the patient relapsed a few months later and died due to disease progression. Cases of blastic NK-cell leukemia/ lymphoma previously reported are briefly reviewed.
 ...
PMID:Blastic natural killer cell leukemia/lymphoma presenting as overt leukemia. 1177 95

2-Chloro-2'-deoxyadenosine (CdA) is a deoxyadenosine analogue which targets enzymes involved in DNA synthesis, and hence might interfere with the resynthesis step of DNA repair. We tested this hypothesis in resting B cell chronic lymphocytic leukemia (B-CLL) lymphocytes, after firstly characterizing unscheduled DNA synthesis occurring in these cells. We observed that the spontaneous incorporation of [methyl-3H]thymidine (dThd) into DNA of B-CLL cells was not completely inhibitable by hydroxyurea (HU) which blocks DNA replication. In addition, in the presence of HU, dThd incorporation could be upregulated by UVC radiation or DNA alkylation, without re-entry of the cells into S phase. CdA was found to inhibit both spontaneous and upregulated DNA synthesis in B-CLL cells. Phosphorylation of CdA was essential to exert this effect. We finally observed a strong synergistic cytotoxicity between UV light and CdA, which was correlated with activation of caspase-3 and high molecular weight DNA fragmentation, two markers of apoptosis. Taken together, these observations indicate that in B-CLL cells CdA inhibits unscheduled DNA synthesis which represents the polymerizing step of a repair process responsive to DNA aggression. Inhibition of this process by CdA, together with a combined activation of the apoptotic proteolytic cascade by CdA and UV, may explain their synergistic cytotoxicity.
Leukemia 2002 Jan
PMID:2-Chloro-2'-deoxyadenosine inhibits DNA repair synthesis and potentiates UVC cytotoxicity in chronic lymphocytic leukemia B lymphocytes. 1184 Feb 61

Peripheral (post-thymic) T-cell lymphoma consists of a wide spectrum of disorders with marked differences in biology and behavior. Proper classification is pivotal for evaluating treatment results, and most studies performed a decade ago lump together different disease entities and cannot be interpreted. With improved use of immunophenotyping and molecular methods for these disorders, their exact nature is better defined in the Revised European-American Lymphoma and subsequent World Health Organization (WHO) classifications. The WHO classification of post- thymic T/natural killer (NK)-cell lymphoma consists of 15 entities, including about 30% that are unclassified cases. A wide range in incidence exists between different populations, but it is likely to be lower than previously estimated. Certain entities, like nasal/nasal-type T/NK-cell lymphoma and human T-cell leukemia/lymphoma virus 1, are much more prevalent in certain racial groups and show exquisite viral association. In these entities as a group, prognosis and treatment seem inferior to those of their B-cell counterparts, but treatment must be tailored to the exact pathologic diagnosis and prognostic index. Aggressive combination chemotherapy appears to be curative for certain entities (eg, anaplastic lymphoma kinase-positive), whereas purine analogues may be useful for low-grade entities. The role of autologous and allogeneic stem cell transplantation is still poorly defined. Specific antibody-based therapy is also on the horizon.
 ...
PMID:Peripheral T-cell lymphoma. 1216 19

Wild-type Wilms' tumor gene WT1 is expressed at high levels not only in most of acute myelocytic, acute lymphocytic, and chronic myelocytic leukemia, but also in various types of solid tumors including lung cancer. We tested the ability of the gene product (WT1) to serve as a target antigen for tumor specific immunotherapy both in human in vitro system and mouse in vivo system. In the latter, we can evaluate the efficacy and the side effects of WT1 vaccination in vivo. In the human in vitro system, two WT1 peptides that contain HLA-A2.1 binding anchor motifs were determined to bind to HLA-A2.1 molecules. Peripheral blood mononuclear cells (PBMC) from an HLA-A2.1-psitive donor were repeatedly stimulated in vitro with TAP-deficient T2 cells pulsed with each of these two peptides, and CD8-positive cytotoxic T lymphocytes (CTLs) that specifically lyse WT1-expressing, HLA-A2.1-positive tumor cells were induced. Other groups also have succeeded in generating CTLs which specifically lyse WT1-expressing leukemia cells, and which do not inhibit colony-formation of normal hematopoietic cells that express WT1 at physiological levels. In the mouse in vivo system, immunization of C57BL/6 mice with one WT1 peptide with relatively high binding affinity for H-2D(b) molecules, which contain H-2D(b) binding anchor motifs, induced CTLs, which specifically lysed WT1-expressing tumor cells in an H-2D(b)-restricted manner. Furthermore, mice immunized with the WT1 peptide (peptide vaccination) or WT1 cDNA (DNA vaccination) rejected challenges by WT1-expressing tumor cells and survived with no signs of auto-aggression to WT1-expressing normal organs by the induced CTLs. The WT1 protein has been identified as a novel tumor antigen and recent investigations provide a rationale for developing WT1-based adoptive T cell therapy and vaccination against various kinds of malignant neoplasms.
 ...
PMID:WT1 as a novel target antigen for cancer immunotherapy. 1218 20

Aggressive adult T-cell leukemia-lymphoma (ATL) generally has a very poor prognosis. Deoxycoformycin (DCF, pentostatin), an inhibitor of adenosine deaminase, has shown promising therapeutic efficacy for ATL. To develop a new effective therapy against aggressive ATL, we carried out a multicenter phase II study of DCF-containing combination chemotherapy. Sixty-two previously untreated patients with ATL (34, 21, and 7 patients with diseases of the acute, lymphoma, and unfavorable chronic types, respectively) were enrolled, but 2 were ineligible because they were judged to be favorable chronic types. A regimen of 1 mg/m2 vincristine intravenously on days 1 and 8, 40 mg/m2 doxorubicin intravenously on day 1, 100 mg/m2 etoposide intravenously on days 1 through 3, 40 mg/m2 prednisolone orally on days 1 and 2, and 5 mg/m2 DCF intravenously on days 8, 15, and 22 was administered every 28 days for 10 cycles unless disease progression or toxic complications occurred. Fifty-two percent of 60 eligible patients responded (95% confidence interval [CI], 38%-65%), with 17 patients (28%) achieving a complete response (CR) (95% CI, 17%-41%) and 14 achieving a partial response. The CR rate was inferior to those of both the previous Japan Clinical Oncology Group (JCOG) study (JCOG8701, 43%), a 9-drug combination chemotherapy of the second generation, and the subsequent JCOG9303 study (35%), a granulocyte colony-stimulating factor-supported, dose-intensified, 9-drug regimen. The median survival time of the 60 eligible patients in JCOG9109 was 7.4 months, and the estimated 2-year survival rate was 15.5%; these results were identical with those of JCOG8701 but inferior to those of JCOG9303. Grade 4 neutropenia and infection of grade 3 or greater were frequent (67% and 22%, respectively), and treatment-related death was observed in 4 patients (7%), septicemia in 2, and cytomegalovirus pneumonia in 2. We conclude that DCF-containing combination chemotherapy is not a promising regimen against aggressive ATL.
 ...
PMID:Deoxycoformycin-containing combination chemotherapy for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study (JCOG9109). 1262 52

Natural killer (NK) cell leukemia and lymphoma represent rare conditions with heterogeneity of biologic behavior, prognosis, and responsiveness to therapy. The initial diagnosis of NK-cell malignancies can be difficult because of the lack of immunophenotypic clonality markers, morphologic heterogeneity, and a poor correlation between cytomorphology and prognosis. Therapeutic recommendations for NK-cell malignancies are derived from retrospective studies or case reports. Immature NK-cell malignancies often have aggressive behavior with poor prognosis, despite administration of acute myeloid leukemia or acute lymphocytic leukemia induction chemotherapy. The use of high-dose chemotherapy with stem cell rescue resulted in a prolonged survival in a small series of patients. NK-cell malignancies originating from cells with mature phenotypes form a spectrum of diseases with distinct prognosis. Patients with aggressive NK-cell leukemia invariably die within several months. Nasal and nasal-like NK/T-cell lymphomas with limited stage disease often respond to radiation therapy alone or combination with chemotherapy and radiation therapy, with 5-year disease-free survival rates ranging from 30% to 75%. Patients with T-cell large granular lymphocyte leukemia or chronic NK-cell lymphoproliferative disease of granular lymphocytes can have an indolent clinical course with long survival without therapy. However, approximately 66% of patients with T-cell large granular lymphocyte leukemia require low-dose chemotherapy with methotrexate or cyclophosphamide or immunosuppressive therapy with glucocorticosteroids or cyclosporine A for symptomatic cytopenias during the course of their disease.
 ...
PMID:Large granular lymphocyte leukemia and natural killer cell leukemia/lymphomas. 1294 9

Aggressive natural killer-cell leukemia (ANKL) is a rare form of large granular lymphocyte leukemia, which is characterized by a systemic proliferation of NK cells. The clinical features of 22 ANKL cases were analyzed. Hepatomegaly (64%), splenomegaly (55%) and lymphadenopathy (41%) were also frequently observed. Leukemic cells were identified as CD1-, CD2+, surface CD3-, CD4-, CD5-, CD7+, CD8+/-, CD10-, CD11b+/-, CD13-, CD16+, CD19-, CD20-, CD25-, CD33(-), CD34-, CD38+, CD56+, CD122+, HLA-DR+ and TCR-. Two of the 16 cases examined for CD57 were positive and three of the seven cases examined for cytoplasmic CD3. Epstein-Barr virus was detected in the tumor cells of 11 of the 13 cases examined. No common cytogenetic abnormalities were identified and 6q anomaly was detected in only one. Three of 13 patients treated with chemotherapy containing anthracycline/anthraquinone attained complete remission, in contrast to none of the eight who were treated with regimens without anthracycline. Although the overall prognosis was poor with a median survival of 58 days, those who attained remission showed better prognosis (P=0.005). These findings suggest that ANKL is an entity of mature cytotoxic NK-cell neoplasms with distinct phenotype and disease presentations. Intensive treatment for ANKL may result in a better prognosis.
Leukemia 2004 Apr
PMID:Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells. 1496 Oct 41

We report 5 cases of Aggressive Natural Killer-Cell Leukemia (ANKL) diagnosed and treated in our institution within a period of 5 years. Presented are the clinical, hematological, immunophenotypic, immunogenotypic and cytogenetic data. ANKL is a very rare disorder. On review of the English-language literature only 68 published cases were identified. Analysis was performed on a total number of 73 cases (68 from the literature and the series of 5 presented hereby). Presented and discussed are the epidemiology, clinical picture, morphology, cell marker, immunogenotype, cytogenetics, and survival data of the analysis, as well as the associations with the Epstein-Barr virus (EBV). To our knowledge this is the largest series of cases of ANKL analyzed and therefore it is hoped to contribute towards a better characterization of the disorder.
 ...
PMID:Aggressive Natural Killer-Cell Leukemia: report of five cases and review of the literature. 1562 55

The hexapeptide Thr-Gly-Glu-Asn-His-Arg (HLDF-6), which was first identified as an active fragment of the human leukemia differentiation factor (HLDF) molecule, displays differentiation-inducing, neuroprotective and anti-drug abuse activities. Most of its in vivo effects were revealed only on male animals. We have studied HLDF-6 effects on a variety of organism functions and behavioral reactions, which are known to be dependent on androgen steroid hormones, both on castrated and normal (sham-operated) animals. Male NMRI mice were castrated or sham-operated at the age of 55 days (after puberty). After that, HLDF-6 peptide was injected daily during 3 weeks, followed by behavioral, morphological and biochemical testing. HLDF-6 increased testosterone level (1.5- to 2-fold) both in sham-operated and castrated animals. Sexual activity and pain sensitivity, which are strongly reduced in castrates, were completely or partially recovered by HLDF-6. At the same time, the peptide caused some effects similar to castration in sham-operated animals: aggression and locomotor activity were decreased; oral grooming was prolonged. Morphological studies of accessory sex glands showed that HLDF-6 partially normalizes the morphology and functional activity of seminal vesicles in castrates, but it does not prevent castration-induced apoptosis of prostate epithelial cells. Based on these observations, we can assume that HLDF-6 peptide displays at least two effects on androgen hormones metabolism in males: it stimulates testosterone biosynthesis by both testes and adrenals and simultaneously inhibits its conversion to dihydrotestosterone (DHT), most probably by diminution of 5alpha-reductase isoform 1 mRNA expression.
 ...
PMID:HLDF-6 peptide affects behavioral reactions and organism functions dependent on androgen hormones in normal and castrated male mice. 1568 Apr 77


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>