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At least 865 records · Page 48Linked to original sources
PubMed1984

[Chemotherapy of chronic myelogenous leukemia in blastic crisis--vindesine, cytosine arabinoside prednisolone combination therapy].

Twenty patients with chronic myelogenous leukemia in terminal transformation were treated with regimen incorporating vindesine, prednisolone and additional cytosine arabinoside. Of the 19 patients in blastic crisis, complete remission was achieved in 13 (68.4%). All four patients with lymphoid morphology, and nine of the eleven patients with myeloid morphology, achieved complete remission (81.8%); the four with monocytoid morphology did not. One patient in accelerated phase also attained complete remission. The present results indicate that the regimen incorporating vindesine-cytosine arabinoside-prednisolone should be treatment of choice in CML-BC with lymphoid morphology and myeloid morphology as well.

Adolescent↗
PubMed1983

Accumulation of guanine-cytosine-enriched low M.W. DNA fragments in lymphocytes of patients with systemic lupus erythematosus.

The fate of the newly synthesized DNA in peripheral blood lymphocytes from patients with systemic lupus erythematosus was examined. After lymphocytes were stimulated with the mitogen phytohemagglutinin (PHA), DNA was pulse-labeled with radioactive thymidine and was analyzed by sucrose density gradient centrifugation. Two classes of DNA were identified; the main DNA fraction that migrated to the same position as that of control samples, and low m.w. DNA fragments. The low m.w. DNA fragments were further characterized: i) The amount of low m.w. fragments increased with increasing time of culture after PHA stimulation. ii) The guanine cytosine content was 47% of the total bases at 4 days after PHA stimulation. iii) The base composition was similar to that of DNA fragments isolated from DNA/anti-DNA antibody immune complexes. These results lead us to propose that guanine cytosine-enriched low m.w. DNA fragments accumulate in cells after nuclear DNA is degraded, and that these fragments may serve as a primary source of autoantigen for anti-DNA antibody production. In addition, they may interfere with normal cellular metabolism.

Base Sequence↗
PubMed1980

[Acute leukaemia during pregnancy: favourable course of pregnancy in two patients treated with cytosine arabinoside and anthracyclines (author's transl)].

A report of two cases of acute leukaemia discovered during pregnancy. The first was treated from the 24th week with cytosine arabinoside, daunorubicine and vincristine and then rubidazone. Only an incomplete remission was obtained. The pregnancy ended with the birth at the 36th week of a normal child, which remains well at the age of 13 months. The second patient received during the 29th week of pregnancy chemotherapy combining cytosine arabinoside and daunorubicine. Signs of foetal distress appeared at 31 weeks. Delivery took place during the 33rd week in a phase of aplasia. The child was born apparently dead and was resuscitated. A complete remission of the leukaemia was obtained. The child was well at the age of 13 months. A transient neutropaenia was noted at the age of 2 months in both children.

Adult↗
PubMed1981

Treatment of patients over 50 years of age with acute myelogenous leukemia with a combination of rubidazone and cytosine arabinoside, vincristine, and prednisone (ROAP).

We administered a combination of rubidazone, cytosine arabinoside, vincristine, and prednisone (ROAP) to 91 patients with acute myelogenous leukemia who were 50 yr of age or older. These patients had been identified in previous studies to be a group with a relatively poor prognosis. One-third of the patients had an antecedent hematologic disorder prior to treatment. Forty patients (48%) obtained a complete hematologic and clinical remission. A history of an antecedent hematologic disorder, male sex, and absence of Auer rods were adverse factors for achieving remission in this older population. More than half of the patients achieved remission in one course. The major cause of failure to obtain a remission was death due to infection, 40% of which were caused by fungi. Resistance to chemotherapy, although uncommon, was noted more frequently in patients with an antecedent hematologic disorder. Univariate and multivariate prognostic factor analysis was used to compare these patients with a historical control group treated with a program in which adriamycin was used instead of rubidazone (AdOAP). No significant difference in remission rate was detected. Cyclocytidine was used as a maintenance agent in this study, and while the median remission duration was only 37 wk, 30% of patients are expected to be in remission for 2 yr. Chemotherapy programs combining an anthracycline with cytosine arabinoside, given to older patients in similar fasion to younger patients will achieve remissions in one-half of a group of older patients. These remissions are of comparable quality to those of younger patients. Mathematical models derived from analysis of prognostic factors are of use in identifying patients likely to fail these programs who are in need of innovative approaches to treatment.

Aged↗
PubMed1977

Effects of acronycine, bleomycin and cytosine arabinoside on the cell cycle. Some aspects of their interaction with radiation determined by pulse cytophotometry.

The influence of three chemotherapeutic agents, acronycine, bleomycin and cytosine arabinoside, alone and combined with radiation, on cell cycle progression and viability of L-cells was examined. The percentages of cells in G1, S and (G2 + M)-phases as derived from pulse cytophotometric DNA distribution patterns were recorded as a function of exposure time. After 24-h treatment with 10 microgram/ml acronycine, 46.4% of cells were accumulated in (G2 + M)-phase compared to 12.1% in the controls. This accumulation was significantly enhanced by an irradiation with 150 rads of X-rays resulting in arresting 63.1% of cells in this phase. Similar findings were obtained after a 24-h treatment with 100 microgram/ml bleomycin. 54.4% of cells were arrested in (G2 + M)-phase by the chemical treatment alone, while the combined treatment, bleomycin and radiation, yielded an accumulation of 66.3% of cells in G2 + M. A 24-h exposure to 0.2 microgram/ml cytosine arabinoside (Ara-C) produced a reversible block of 72.8% of cells in S phase compared to 27.4% in the control cultures. This S block was less pronounced after the combined treatment (51.1%). Some implications of the results for combined therapy are discussed.

Acronine↗
PubMed1980

Controlled delivery of an antitumor drug: localized action of liposome encapsulated cytosine arabinoside administered via the respiratory system.

Cytosine arabinoside in free or liposome encapsulated form was administered to the lungs of rats via intratracheal instillation. The free drug rapidly left the lung (T 1/2 = 40 min), while the encapsulated drug remained in the lung for a prolonged period (T 1/2 = 8 hr). Free cytosine arabinoside effectively inhibited DNA synthesis (measured by [14C]thymidine incorporation) in the intestine and bone marrow as well as in the lung. By contrast, liposome-encapsulated drug effectively inhibited DNA synthesis in the lung, but similar doses failed to inhibit DNA synthesis in other tissues. The metabolism of free and encapsulated drug were similar in that the same products resulted, namely the inactive catabolite uracil-beta-D-arabinofuranoside and the phosphorylated anabolites of cytoside arabinoside. These results suggest that the action of an antitumor drug can be confined to a single organ through the use of a liposomal drug delivery system.

Animals↗
PubMed1979

Treatment of acute nonlymphocytic leukemia: use of anthracycline-cytosine arabinoside induction therapy and comparison of two maintenance regimens.

Patients with acute nonlymphocytic leukemia were given remission induction therapy consisting of cytosine arabinoside and an anthracycline. Those patients who experienced complete remission received two courses of consolidation therapy and were randomized to receive maintenance therapy consisting of either daily chemotherapy with reinforcements every 3 mo or reinforcement therapy only every 6 wk. The overall complete remission rate was 66%, with 80% complete remission for previously untreated patients less than 60 yr of age who did not have a prior history of malignancy. Remission durations were the same for patients treated with both maintenance regimens. The major determinant for successful remission induction therapy was patient age, with older patients frequently succumbing to intercurrent infection. Documented leukemic cell resistance to the therapy employed was only rarely encountered. Once remission was achieved, age was no longer a determinant of patient survival, since duration of remission was independent of age. Remission durations were directly related to leukemic cell retention of cytosine arabinoside triphosphate. Hence therapy for acute nonlymphocytic leukemia can be divided into two separate areas: remission induction and remission maintenance.

Adolescent↗
PubMed1995

All-trans retinoic acid and low-dose cytosine arabinoside for the treatment of 'poor prognosis' acute myeloid leukemia.

Thirty-three patients with 'poor prognosis' acute myeloid leukemia, no longer suitable for aggressive chemotherapy, were treated with daily oral all-trans retinoic acid (45 mg/m2) daily and subcutaneous cytosine arabinoside (20 mg standard dose twice a day, day 1 to 10, every 4 weeks). Seventeen patients were males and 16 females, the median age was 67 (range 39-82 years). Eleven patients were at onset of disease, 15 were refractory to previous conventional therapies, three were in first relapse and three in second relapse and one patient had a secondary AML. Seventeen patients had a bone marrow blast infiltration < 50% and 16 > or = 50%. A total of 16 (48%) patients entered complete remission; the rate of complete remission increased to 88% in those patients (n = 17) with < 50% blast infiltration at the time of entering the study. Seventeen patients (52%) were resistant. The difference in response to therapy, according to bone marrow blast percentage (< or > or = 50%), was statistically significant (P < 0.001). Median duration of complete remission was 34.4 weeks (range 6.4-62.8). Mild to moderate hematologic toxicity was the most common side-effect. In conclusion all-trans retinoic acid and low-dose cytosine arabinoside appears to be an effective regimen for inducing complete remission in 'poor prognosis' acute myeloid leukemia and patients with < 50% bone marrow infiltration are likely to represent the ideal target to receive this combination therapy.

Adult↗
PubMedDate not supplied

Cyclophosphamide (NSC-26271) maintenance therapy after a second remission of childhood acute lymphoblastic leukemia: comparative clinical trial (standard dose versus intermittent high dose versus cyclophosphamide plus cytosine arabinoside (NSC-63878)).

Children with acute lymphoblastic leukemia who had experienced only one relapse were reinduced into remission using a 6-week induction course of prednisone and vincristine. One hundred fifty-one children who achieved a second complete marrow remission were randomly assigned to one of three cyclophosphamide treatment groups for maintanence. Forty-one children received standard-dose cyclophosphamide (3 mg/kg/day), 55 received intermittent high-dose cyclophosphamide (10 mg/kg/day for 4 days out of 14), and 55 received a combination of oral cyclophosphamide (3 mg/kg/day) plus cytosine arabinoside (3 mg/kg/week im). The standard-dose cyclophosphamide regimen resulted in a remission maintenance time of 109 days and was the least toxic of the three maintenance regimens. Giving cyclophosphamide on an intermittent high-dose schedule or combining it with cytosine arabinoside did not increase the remission maintanence time (105 days).

Bone Marrow↗
PubMedDate not supplied

Inhibition of deamination of 14C-cytosine arabinoside (NSC-63878): a useful biologic assay for tetrahydrouridine (NSC-112907).

Inhibition of the deamination of 14C-cytosine arabinoside by two lots of tetrahydrouridine was studied in monkey serum. The average inhibition of deaminase activity was 78% for tetrahydrouridine lot AJ39 (1.0 muM) when the concentration of cytosine arabinoside ranged from 44.2 to 170.7 muM; under the same conditions tetrahydrouridine lot AJ22 inhibited deamination by an average of 68%. Apparent Ki values were 0.26 muM for AJ39 and 0.43 muM for AJ22. The assay may be used to check the relative biologic activity of various lots of tetrahydrouridine.

Animals↗
PubMed1994

[Neutropenic typhlitis: a frequently missed complication of aplasia-inducing tumor therapy with a possible association to the combination of etoposide with high-dose cytosine-arabinoside].

Neutropenic typhlitis (NPT) was observed in 4 of 5 adult patients with acute leukemia treated with etoposide (VP16; 100 mg/m2/d for 6 days) and high-dose cytosine-arabinoside (HD ARAC, 2 g/m2 twice daily for 6 days) in a period of 11 months. One additional patient developed NPT after combination therapy with amsacrine (mAMSA, 120 mg/m2/d for 5 days) and etoposide (80 mg/m2/d for 5 days) during the same period. These 5 cases of NPT meant a drastic rise in the incidence of NPT at our institution, where a careful retrospective review of the charts of the 128 adult patients with leukemia treated during the preceding 5 years revealed only one case of NPT. Nonsurgical treatment led to recovery in all cases. No recurrence of NPT was observed during 3 further courses of aplasia with the use of selective (2 patients) or complete (1 patient) bowel decontamination. Etoposide may potentiate the gastrointestinal toxicity of high-dose cytosine-arabinoside with a higher incidence of NPT.

Acute Disease↗
PubMed1993

Synthesis and biological activity of 1-(2-deoxy-2-C-fluoromethyl- and 2-C-hydroxymethylarabinofuranosyl)-cytosines.

We newly synthesized 1-(2-deoxy-2-C-fluoromethyl- and 2-C-hydroxymethyl-arabinofuranosyl)cytosines and evaluated their biological activities. The syntheses of these compounds were achieved by radical deoxygenation of tert-alcohol of 2'-position of the corresponding fluorohydrine and acetoxymethyl derivative. 1-(2-Deoxy-2-C-fluoromethylarabinofuranosyl)cytosine (5) showed potent antileukemic and anticytomegalovirus activities.

Antineoplastic Agents↗
PubMed1996

Forced expression of cytidine deaminase confers resistance to cytosine arabinoside and gemcitabine.

Genes that confer cellular resistance to cytotoxic agents have potential applications both for marrow protection following cancer chemotherapy and as dominant selectable markers for the selection of genetically modified hematopoietic cell populations in vivo. Cytidine analogues, including cytosine arabinoside (Ara-C), 2',2'-difluorodeoxycytidine (gemcitabine), and other drugs represent a clinically important class of chemotherapeutic agents for which no drug resistance gene has yet been described. Studies were performed to determine whether forced expression of a gene encoding the enzyme cytidine deaminase can confer resistance to cytosine arabinoside (Ara-C) and gemcitabine in vitro. A pooled population of NIH3T3 cells overexpressing cytidine deaminase from a retroviral construct based on the LXSN-vector (LCDSN) demonstrated a 4.5-fold increased resistance to Ara-C based on the 50% inhibitory concentration (ID50) and a 3.7-fold increased resistance to Ara-C based on the 80% inhibitory concentration (ID80) relative to cells transduced with a control vector. In the hemopoietic cell line CCRF-CEM, the same retroviral construct conferred a 2.1-fold increased resistance to Ara-C by ID50 and a 3.0-fold increased resistance to Ara-C by ID80 relative to cells transduced with a control vector. CEM cells transduced with LCDSN were also resistant to gemcitabine (2.4-fold by ID50 and 2.5-fold by ID80). Furthermore, Ara-C-resistance could be completely reversed in LCDSN-transduced CEM cells by a specific inhibitor of cytidine deaminase, tetrahydrouridine (THU). Expression of the transgene was confirmed by RNase-protection assay and by an enzyme activity assay. These results provide the first direct evidence that forced expression of cytidine deaminase confers cellular resistance to Ara-C and gemcitabine.

3T3 Cells↗
PubMed1976

Herpes simplex encephalitis: treatment with surgical decompression and cytosine arabinoside.

Herpes simplex encephalitis in a 21-year-old man presented as a flu-like illness, followed by inappropriate behaviour, drowsiness and focal neurologic signs. Investigations indicated a lesion in the right temporal lobe. The diagnosis was confirmed by isolation of the virus from a cerebral biopsy. Pronounced clinical improvement was noted when cytosine arabinoside therapy was started in the postoperative period. This report supports the observation by some authors that cytosine arabinoside may be of value in the treatment of herpes simplex encephalitis.

Adult↗
PubMed1998

[Low-dose oral etoposide and subcutaneous injection of low-dose cytosine arabinoside (Et-A non i.v.) with or without minimum anthracycline for refractory acute non-lymphoblastic leukemia].

Low-dose oral etoposide (50 mg for 10 to 14 days) and low-dose subcutaneous injection of cytosine arabinoside (15-20 mg/12 hours for 14 to 17 days) (Et-A non i.v.) were given to refractory acute non-lymphoblastic leukemia patients. Case 1 was a 47-year-old woman who had a relapsed M0. B-DOMP therapy failed but she recovered from severe infection. She had to go home to take care of her children. Et-A non i.v. was given for 14 days and 11 mg of mitoxantrone was added on the 3rd day. She achieved a complete remission (CR). Case 2 was a 72-year-old woman classified M4. Low-dose cytosine arabinoside (Ara-C) with additional daunorubicin (DNR) therapy failed. She became weaker due to the gastrointestinal toxicity of DNR. Et-A non i.v. was tried. Oral etoposide (Et) for 10 days and Ara-C for 14 days proved effective, and she achieved CR. Case 3 was a 59-year-old man with M4 developed from myelodysplastic syndrome, complicated with infection. Ara-C low-dose therapy was begun, but it was not effective. It was switched to Et-A non i.v., 40 mg of DNR was added, with 12 mg of mitoxantrone and double administration of 3 mg of vindesine. He also achieved CR. Et-A non i.v. therapy is effective and available for induction therapy with low toxicity and convenient to daily life.

Aged↗
PubMed1996

Treatment of human B-cell precursor leukemia in SCID mice using a combination of the investigational biotherapeutic agent B43-PAP with cytosine arabinoside.

Combined immunochemotherapy regimens using the investigational biotherapeutic agent B43(anti-CD19)-poke-weed antiviral protein (PAP) immunotoxin may offer an effective treatment for refractory B-cell precursor leukemias. The purpose of the present study was to explore and identify effective combinations of B43-PAP with standard chemotherapeutic drugs, including the anthracyclin doxorubicin, the epipodophyllotoxin etoposide, the nitrosurea carmustine, and the antimetabolite cytosine arabinoside. Here, we report that the B43-PAP plus cytosine arabinoside combination has potent antileukemic activity against human B-cell precursor leukemia in SCID mice and leads to 100% long-term event-free survival from an otherwise invariably fatal leukemia. Surprisingly, none of the other treatment protocols tested, including combinations of B43-PAP with carmustine, doxorubicin, or etoposide, proved more effective than B43-PAP alone.

Animals↗
PubMed2003

Allosteric activator domain of maintenance human DNA (cytosine-5) methyltransferase and its role in methylation spreading.

The human maintenance DNA (cytosine-5) methyltransferase (hDNMT1) consists of a large N-terminal regulatory domain fused to a catalytic C-terminal domain by randomly repeated Gly-Lys dipeptides. Several N-terminal deletion mutants of hDNMT1 were made, purified, and tested for substrate specificity. Deletion mutants lacking 121, 501, 540, or 580 amino acids from the N-terminus still functioned as DNA methyltransferases, methylated CG sequences, and preferred hemimethylated to unmethylated DNA, as did the full-length hDNMT1. Methylated DNA stimulated methylation spreading on unmethylated CpG sequences for the full-length and the 121 amino acid deletion hDNMT1 equally well but not for the mutants lacking 501, 540, or 580 amino acids, indicating the presence of an allosteric activation determinant between amino acids 121 and 501. Peptides from the N- and C-termini bound methylated DNA independently. Point mutation analysis within the allosteric region revealed that amino acids 284-287 (KKHR) were involved in methylated DNA-mediated allosteric activation. Allosteric activation was reduced in the double point mutant enzymes D25 (K284A and K285A) and D12 (H286A and R287A). Retinoblastoma gene product (Rb), a negative regulator of DNA methylation, bound to the allosteric site of hDNMT1 and inhibited methylation, suggesting Rb may regulate methylation spreading.

Allosteric Regulation↗
PubMed2003

Conservation of Dnmt1o cytosine methyltransferase in the marsupial Monodelphis domestica.

Imprinted genes have been identified in both eutherian mammals and in marsupials. In eutherian species, there is a conservation of the imprinting process, both in terms of the genes imprinted and the epigenetic inheritance mechanism. In the mouse, the inheritance of gametic methylation patterns depends on an oocyte-derived isoform of the Dnmt1 (cytosine-5)-methyltransferase protein, Dnmt1o, which functions during preimplantation development to maintain methylation patterns on imprinted alleles. To determine if this component of genomic imprinting is also found in marsupials, Dnmt1 isoforms were examined in somatic cells and germ cells of the South American opossum Monodelphis domestica. There is a Dnmt1o protein in Monodelphis oocytes that is synthesized, as in the mouse, from a different transcript than the somatic Dnmt1 protein. Thus, an essential component of imprinting in eutherian mammals is found in a marsupial species, suggesting that marsupials and eutherian mammals imprint their genes with the same methylation-dependent mechanism.

Amino Acid Sequence↗