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

Monocytes/macrophages and endothelial cells express tissue factor (TF), an initiator for blood clotting pathway, following their activation accompanied by immune response and/or inflammation. This TF expression results in thrombin generation and fibrin formation around these cells and possibly participates in host-defense mechanism. TF expression by these cells is also a risk-factor to vascular diseases including arteriosclerosis and thrombosis. In cancer and leukemia patients elevation of their plasma TF level associated with DIC and related coagulation disorders.
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PMID:[Current scopes on tissue factor: its physiological function and relationship with coagulation diseases]. 802 93

Efficacy and safety of i.v. dermatan sulphate (DS) and heparin (H) in controlling laboratory alterations due to DIC were compared in 10 patients with acute leukaemia, in a prospective, randomised pilot study. The time courses of the coagulation and fibrinolysis markers for DIC were similar in the two treatment groups except for activated partial thromboplastin time and thrombin time, which were prolonged in the H but not in the DS group. Blood product support tended to be greater in the H than in the DS group. DS appears to be as effective as H in controlling thrombin production during leukaemic cytolysis and may represent a safer alternative to H in the management of DIC in acute leukaemia.
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PMID:Dermatan sulphate for the treatment of disseminated intravascular coagulation (DIC) in acute leukemia: a randomised, heparin-controlled pilot study. 802 9

The effects of resistance modifiers (RM) on the cytotoxicity of mafosfamide (MAF), bis-chloroethylnitrosourea (BCNU) and dacarbazine (DTIC) were evaluated by the MTT colorimetric assay in isolated lymphocytes and blast cells derived from patients with chronic lymphatic leukaemia (CLL; n = 28) and acute myeloid leukaemia (AML; n = 30), or from healthy donors (n = 19). Pentoxifylline (PTX) has been shown to restore sensitivity to alkylating drugs by interfering with DNA repair. PTX (10 microM) significantly sensitised leukaemic blasts to the cytotoxic effect of MAF. In 8 out of 30 AML samples, sensitisation ratios (SRs; i.e. cytotoxic drug ID50s in the presence or absence of RM) for MAF in the presence of PTX were > 2 ranging up to 4.2. Inhibition of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) by O6-benzylguanine (O6-BG; 50 microM) enhanced the cytotoxicity of DTIC in CLL lymphocytes. SRs > 2 for DTIC in the presence of O6-BG were observed in 7 out of 28 CLL specimens. Sensitisation was generally greater in the more chemo-resistant specimens. Ethacrynic acid (EA; 1 microM), an inhibitor of glutathione-S-transferases (GST), failed to influence the cytotoxicity of alkylating agents in any cell type. Also, all examined RMs did not sensitive leukaemic cells to the cytotoxic effect of BCNU. The data show significant chemosensitisation of leukaemic cells to alkylating agents by PTX and O6-BG, indicating a potential clinical use of these substances as RM in patients.
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PMID:Chemosensitisation of alkylating agents by pentoxifylline, O6-benzylguanine and ethacrynic acid in haematological malignancies. 829 28

A 75-year-old female was admitted to our hospital because of fever and hypotension. The peripheral blood showed 400 leukocytes/microliters with 13,000/microliters platelets. Bone marrow puncture revealed that NCC stood at 14,000 with 50.0% blasts. The surface characters of the blasts were CD13+, CD33+, and HLA-DR+, and blood culture tests were positive. Coagulation tests revealed DIC. Based on the foregoing results, hypoplastic leukemia was diagnosed accompanied by sepsis and DIC, and was placed on the concomitant administration of a combination of low dose Ara-C and M-CSF. After 14 days of Ara-C administration and 26 days of M-CSF, her clinical symptoms improved, with the peripheral blood showing a WBC of 2,800/microliters and platelet count of 111,000/microliters. The percentage of myeloblasts decreased to 7.0%. After the administration of Ara-C was suspended for 2 weeks, another course of low dose Ara-C plus M-CSF administration was carried out and the patient achieved full remission. M-CSF stimulates not only the production of monocytes but increases the number of neutrophils and platelets through monocytes. It is also expected that tumoricidal activity may be realized by the activation of monocytes. In this patients, the concomitant administration of M-CSF and low dose Ara-C was remarkably effective in treating hypoplastic leukemia with severe complication. This result suggests that M-CSF will be useful for the treatment of leukemia.
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PMID:[Hypoplastic leukemia which achieved remission with administration of M-CSF along with low dose ara-C]. 831 38

The occurrence of aberrant, retrovirus-related proteins is a common finding in immunogenic clones of the triazene-xenogenized L5178Y lymphoma line (L5178Y/DTIC). In clone D-cells, newly expressed 80 kDa antigens related to xenotropic murine leukemia virus env gene products induce specific humoral and cell-mediated responses and possess biologic activity in vivo. To further clarify the relationship between immunogenic properties of clone D and retroviral gene expression, tumor cells were treated in vitro with antisense oligonucleotides complementary to xenotropic and/or polytropic env sequences of murine leukemia virus. The cells were then assayed for expression of antigens recognized by humoral and cell-mediated responses with specificity for clone D. The results demonstrated that inhibition of env mRNA translation adversely affected the expression of immunogenic determinants in the xenogenized tumor cells.
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PMID:Cell-mediated immunity to chemically xenogenized tumors--VI. The effect of cell treatment with retroviral env antisense oligonucleotides. 837 38

We treated 70 patients with acute promyelocytic leukemia (APL) with daily oral 45 mg/m2 all-trans retinoic acid (ATRA) in 2 multi-institutional prospective studies. Of 63 evaluable patients, 21 were resistant to initial induction chemotherapy, 10 were resistant to salvage chemotherapy after relapse, 17 were in the first relapse, 4 in the second relapse, 4 in the third relapse, and 7 were previously untreated. In the first study with ATRA from China, 18 (82%) of 22 evaluable patients achieved CR within 8 to 53 days with a median of 29 days. Initial peripheral leukemia cell counts were significantly less in the CR cases (p < 0.01). They were less than 100/mm3 in 17 of 18 CR cases, and more than 200/mm3 in all failure cases. Patients achieving CR received standard consolidation and maintenance chemotherapies, and the 16-month predicted continuing CR rate is 60%. Based on the first study, in the second study with ATRA from Hoffmann-La Roche AG, if initial peripheral leukemia cell counts were more than 200/mm3, chemotherapy was first given and then ATRA was started. Of 41 evaluable patients, 36 (88%) achieved CR within 11 to 91 days with a median of 34 days. Of 3 patients who received preceding chemotherapy due to high leukemia cell counts, 2 achieved CR. Morphological evidence of differentiation was noted in all CR cases, with Auer rods in mature segmented neutrophils in 13 cases. The clinical signs of DIC decreased rapidly within a few days and disappeared in CR cases. Toxicities attributable to ATRA were minimal and included cheilitis, xerosis, dermatitis, gastrointestinal disorders, bone pain, liver damage and high serum triglyceridemia.
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PMID:[Differentiation therapy of acute promyelocytic leukemia with all-trans retinoic acid]. 839 Feb 26

We treated 70 patients with acute promyelocytic leukemia (APL) with daily oral 45 mg/m2 all-trans retinoic acid (ATRA) in 2 multi-institutional prospective studies. Of 63 evaluable patients, 21 were resistant to initial induction chemotherapy, 10 were resistant to salvage chemotherapy after relapse, 17 were in the first relapse, 4 in the second relapse, 4 in the third relapse, and 7 were previously untreated. In the first study with ATRA from China, 18 (82%) of 22 evaluable patients achieved CR within 8 to 53 days with a median of 29 days. Initial peripheral leukemia cell counts were significantly less in the CR cases (p < 0.01). They were less than 100/cmm in 17 of 18 CR cases, and more than 200/cmm in all failure cases. Patients achieving CR received standard consolidation and maintenance chemotherapies, and the 16-month predicted continuing CR rate is 60%. Based on the first study, in the second study with ATRA from Hoffmann-La Roche AG, if initial peripheral leukemia cell counts were more than 200/cmm, chemotherapy was first given and then ATRA was started. Of 41 evaluable patients, 36 (88%) achieved CR within 11 to 91 days with a median of 34 days. Of 3 patients who received preceding chemotherapy due to high leukemia cell counts, 2 achieved CR. Morphological evidence of differentiation was noted in all CR cases, with Auer rods in mature segmented neutrophils in 13 cases. The clinical signs of DIC decreased rapidly within a few days and disappeared in CR cases. Toxicities attributable to ATRA were minimal and included cheilitis, xerosis, dermatitis, gastrointestinal disorders, bone pain, liver damage and high serum triglyceridemia.
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PMID:[Differentiation therapy of acute promyelocytic leukemia with all-trans retinoic acid]. 843 55

Two cases of unexpected post-partum death of women with acute leukemia are described. In the first case (1st pregnancy) the diagnosis (acute promyelocytic leukemia: M3) was performed one week before delivery and death occurred 3 days later, because of hemorrhagic and renal DIC complication. Since one month before hospitalization, laboratory exams indicated a serious hematological pathology and no further exams were carried out by the physicians, elements of professional fault were recognized in them, considering that because of the diagnostic omission it was impossible to make an early diagnosis and thus perform to specific therapy, adopted only in the terminal phase. This specific therapy is able to determine remission from most cases of acute promyelocytic leukemia. In the second case (2nd pregnancy) the diagnosis (acute myelomonocytic leukemia: M4) was performed only postmortem because, during the whole pregnancy, no signs of disease were evident. After a few hours from the spontaneous delivery, death occurred as a result of an intractable + hemorrhagic syndrome caused by primary hyperfibrinolysis and repeated episodes of cardiac arrest, without possibility of recognizing it. The medical procedures for this case, both throughout pregnancy and terminal phases, appeared free of censure.
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PMID:[2 fatal cases of acute myeloid leukemia (M3, M4) during pregnancy]. 853 3

O6-Methylguanine-DNA methyltransferase (MGMT) is an important DNA repair protein that plays a key role in cancer chemotherapy by alkylating agents such as carmustine (BCNU) and Dacarbazine (DTIC). Therapy by BCNU and DTIC is reduced by dose-limiting hematological toxicity as a result of low MGMT repair activity in bone marrow cells. In this study, we have constructed a Moloney murine leukemia virus retroviral vector containing the human mgmt gene. High-titer retrovirus producer cells lines have been generated. Retroviral-mediated transfer of the human mgmt gene into murine multi-potent hematopoietic stem cells, FDCP-1, resulted in the expression of a high level of MGMT activity. In comparison with the control cells that were transduced with the parent vector, the MGMT-expressing clones were considerably more resistant to the cytotoxicity of the methylating agents, such as N-methyl-N'-nitro-N-nitrosoguanidine, N-nitroso-N-methyl-urea, and temozolomide, as well as the chloroethylating agents 1-(2-chloroethyl)-1-nitrosourea and BCNU. The protection provided by MGMT could be eliminated by the MGMT inactivator O6-benzylguanine. Thus, the principal lethal lesions produced by these alkylating agents in the murine hematopoietic stem cells and the MGMT deficiency in these cells can be complemented by retroviral-mediated gene transduction.
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PMID:Retrovirus-mediated transfer of the human O6-methylguanine-DNA methyltransferase gene into a murine hematopoietic stem cell line and resistance to the toxic effects of certain alkylating agents. 864 46

A clinical trial was conducted in order to evaluate the therapeutic effect and side-effects of low-dose ATRA in the treatment of acute promyelocytic leukemia (APL). We compared the pharmacokinetic features in normal individuals with single oral ATRA at 15 mg/m2 and 45 mg/m2, respectively. The results showed that maximal plasma concentration (Cpmax) with oral 15 mg/m2 ATRA was high enough (10(-6) M) to induce APL cell differentiation. Based on these results, 27 cases of de novo APL patients were treated with continuous oral ATRA at the dose of 15-20 mg/m2/day and 24/26 evaluable cases (92%) achieved clinical CR after 13 to 67 days of ATRA treatment. No patient experienced RAS and DIC. The Cpmax with a single dose of ATRA on day 1 of treatment and immediately at CR obtained with continuous ATRA in three cases demonstrated similar values in one patient and an approximately two-fold decrease in two patients. More importantly, compared with a relatively well-matched historic group of 20 APL patients treated with high-dose ATRA, our results suggest that low-dose ATRA is as effective as high-dose in treating APL patients and may provide advantages through decreased hyperleukocytosis and other side-effects.
Leukemia 1996 May
PMID:Pharmacokinetics and efficacy of low-dose all-trans retinoic acid in the treatment of acute promyelocytic leukemia. 865 78


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