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Acta Haematologica 1992
Topics: Acute Disease; Adult; Ancitabine; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Humans; Male; Parotitis; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 1384258
DOI: 10.1159/000204597 -
Yao Xue Xue Bao = Acta Pharmaceutica... 1992Resistant variants of HSV-1 wt strain to ACV, CC, DHPG and PFA can be selected after several passages in drug-containing cultures. The degree of resistance of different...
Resistant variants of HSV-1 wt strain to ACV, CC, DHPG and PFA can be selected after several passages in drug-containing cultures. The degree of resistance of different variants varied and emerged at different times. The combination of antiviral agents can delay and even prevent the emergence of drug-resistant variants. At the same time, the concentration, dose and, therefore, toxicity of the antiviral agents can also be reduced. So, it is a feasible method for treating resistant HSV infections. Cross-sensitivity tests showed that ACVr variants are resistant to ACV, DHPG and PFA, but sensitive to CC; PFAr variants are sensitive to ACV, CC and DHPG; CCr variants are sensitive to ACV and DHPG, but resistant to PFA; DHPGr variants are sensitive to ACV, CC and PFA. These results suggest that the study of cross-sensitivity of HSV strains in vitro provide information which will aid the design of suitable therapy for drug-resistant HSV infections.
Topics: Acyclovir; Ancitabine; Animals; Antiviral Agents; Drug Combinations; Drug Resistance, Microbial; Foscarnet; Phosphonoacetic Acid; Simplexvirus; Vero Cells
PubMed: 1382356
DOI: No ID Found -
ORL; Journal For Oto-rhino-laryngology... 1992The degranulation and regranulation process was investigated after alpha-adrenergic stimulation on the rat submandibular gland. The submandibular gland in rat contains...
The degranulation and regranulation process was investigated after alpha-adrenergic stimulation on the rat submandibular gland. The submandibular gland in rat contains both serous and mucous cells. It has earlier been shown that serous cells filled with heavy-metal granules, are markedly more radiosensitive than cells without granules. In experiments with emptying the serous cell of their content of granules by administering an alpha-adrenergic stimulant, cyclocytidine, there has been found a decrease in irradiation damage in salivary gland tissue after irradiation. Injection of cyclocytidine, 150 mg/kg, was given i.p. to the rat. After 1 h there was almost complete depletion of granules in the serous cells, no morphological aberration was seen in the mucous cells. This effect still remained after 6 h. A beginning of regranulation with apical granules was seen 12 h after injection. After 24 h an almost complete regranulation had occurred in the salivary gland serous cells. The mucous cells did not show any morphological aberration. Our intent is to reduce unwanted salivary gland damage in patients with head and neck cancer when treated with radiotherapy. Depletion of heavy-metal granules in serous cells, before irradiation may diminish morphological destruction in the salivary glands. As a nearly total degranulation is present between 1-6 h after stimulation, this should be the optimal time for radiotherapy.
Topics: Ancitabine; Animals; Cytoplasmic Granules; Microscopy, Electron; Radiation Injuries; Rats; Rats, Inbred Strains; Submandibular Gland; Time Factors
PubMed: 1374876
DOI: 10.1159/000276256 -
Proceedings of the Society For... Dec 1991Cyclocytidine (CC), a potent antitumor agent, caused a 2.3- to 5.0-fold increase in [3H]thymidine uptake of rat parotid gland after 3 days of daily administration of 500...
Cyclocytidine (CC), a potent antitumor agent, caused a 2.3- to 5.0-fold increase in [3H]thymidine uptake of rat parotid gland after 3 days of daily administration of 500 mg/kg body wt. Gland weight also showed a 47-67% increase from that of controls. Ablation of the submandibular-sublingual glands prior to initiation of the CC regimen prevented the usual CC-induced increase in [3H]thymidine uptake, but did not inhibit the increase in gland size. It is postulated that CC-induced parotid hyperplasia requires an initial release of growth factors from the submandibular gland; however, enlargement of the parotid gland by CC is independent of such factors.
Topics: Ancitabine; Animals; Hyperplasia; Norepinephrine; Organ Size; Parotid Gland; Rats; Sublingual Gland; Submandibular Gland; Thymidine
PubMed: 1719562
DOI: 10.3181/00379727-198-43317 -
Journal of the Autonomic Nervous System Aug 1991Norepinephrine (NE) concentration of parotid and submandibular glands of young rats was reduced 51% and 39%, respectively at 1 h, and 60% and 47% at 2 h after i.p.... (Comparative Study)
Comparative Study
Norepinephrine (NE) concentration of parotid and submandibular glands of young rats was reduced 51% and 39%, respectively at 1 h, and 60% and 47% at 2 h after i.p. administration of a single dose (500 mg/kg body weight) of the anti-tumor agent, cyclocytidine (CC). For adult rats, the reductions were 44% and 46%, respectively, at 1 h and 54% and 49% at 2 h. This decrease from controls was generally similar to the decrease induced following 1 and 2 h of electrical stimulation (square wave pulses of 4 V, 5 ms duration, and frequency of 16 Hz) of the sympathetic innervation to these glands (young rats, 59% and 58% at 1 h; 66% and 63% at 2 h; for adult rats, 51% and 55% at 1 h and 69% and 53% at 2 h for parotid and submandibular, respectively). The changes in density of beta-adrenoceptors induced by direct nerve stimulation also corresponded to the changes induced by CC (CC induced a decrease in parotid of 12%, compared with a decrease of 11% with electrical stimulation; a 15% and 18% reduction in number of beta-adrenoceptors of submandibular gland was found at 1 h after CC and electrical stimulation, respectively). Compelling evidence for the mechanism of CC action was thus established, showing that CC mimics effects of sympathetic nerve stimulation (inducing reduction in NE concentration and transient change in beta-adrenoceptor density) by causing release of NE from sympathetic nerve endings.
Topics: Ancitabine; Animals; Cyclic AMP; Dihydroalprenolol; Electric Stimulation; Female; Norepinephrine; Parotid Gland; Rats; Rats, Inbred Strains; Receptors, Adrenergic; Submandibular Gland; Sympathetic Nervous System
PubMed: 1719059
DOI: 10.1016/0165-1838(91)90052-5 -
Cancer May 1991Amsacrine (AMSA) and cyclocytidine were studied as retrieval therapy in 122 pediatric patients with acute nonlymphoblastic leukemia (ANLL). Patients either failed to... (Clinical Trial)
Clinical Trial
Amsacrine (AMSA) and cyclocytidine were studied as retrieval therapy in 122 pediatric patients with acute nonlymphoblastic leukemia (ANLL). Patients either failed to achieve sustained initial remissions or were in relapse. Induction therapy consisted of intravenous (IV) AMSA (75 mg/m2) from days 1 to 5 and subcutaneous cyclocytidine (600 mg/m2) from days 1 to 7. Maintenance therapy consisted of IV etoposide (VP-16) (100 mg/m2) for 5 days and IV AMSA (100 mg/m2) on day 1. Of 122 patients, 109 were evaluable. There were 13 early deaths. Ninety-six patients received adequate therapy defined as completion of two courses of therapy. Of these 96 patients, 52 achieved complete remission. Fifteen of 33 patients who failed initial induction achieved complete remission. Eighteen of 39 patients who were resistant to anthracyclines had complete responses. There was no direct evidence of AMSA-induced cardiotoxicity. Remission duration was 28 days to 3 or more years (median, 98 days). AMSA and cyclocytidine were effective retrieval therapy for patients who were in relapse or unresponsive to frontline therapy. Duration of remission was short (median, 98 days).
Topics: Adolescent; Amsacrine; Ancitabine; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Child; Child, Preschool; Etoposide; Female; Humans; Infant; Leukemia, Myeloid, Acute; Male; Pediatrics; Remission Induction
PubMed: 1707336
DOI: 10.1002/1097-0142(19910501)67:9<2235::aid-cncr2820670904>3.0.co;2-2 -
Journal of Medical Virology Jun 1990The antiviral activities of antileukemic drugs 1-beta-D-arabinofuranosylcytosine (Cytarabine; Ara-C), 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine (Ancitabine;... (Comparative Study)
Comparative Study
Antiviral effect of antileukemic drugs N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC) and 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine (cyclo-C) against human cytomegalovirus.
The antiviral activities of antileukemic drugs 1-beta-D-arabinofuranosylcytosine (Cytarabine; Ara-C), 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine (Ancitabine; Cyclo-C), and N4-behenoyl-1-beta-D-arabinofuranosylcytosine (Enocitabine; BH-AC) were evaluated in vitro against human cytomegalovirus (HCMV) in comparison with those of five other antiviral drugs. Both Ara-C and Cyclo-C showed the strongest inhibitory effect to HCMV. BH-AC inhibited the replication of HCMV and depicted almost as the same dose-response curve as Ganciclovir (DHPG). In the presence of Ara-C, Cyclo-C, or BH-AC, triphosphate forms of the nucleoside analogs were detected in the HCMV-infected cells, and synthesis of HCMV DNA was strongly suppressed. Thus, Ara-C, Cyclo-C, and BH-AC were not only antileukemic, but also antiviral in vitro. However, Ara-C and Cyclo-C may not be suitable as anti-HCMV agents, because they are cytotoxic or excreted rapidly in the urine in vivo [Van Voris, 1984; Hirayama et al., 1974]. Because of lower toxicity and longer retention in vivo, BH-AC may be expected as an anti-HCMV agent in patients with leukemia, in addition to serving as an antileukemic drug.
Topics: Ancitabine; Antiviral Agents; Cells, Cultured; Cytarabine; Cytomegalovirus; DNA Replication; DNA, Viral; Fibroblasts; Humans; Nucleotides; Virus Replication
PubMed: 1696958
DOI: 10.1002/jmv.1890310212 -
Neoplasma 1990The basic biochemical characteristics of cyclocytidine hydrochloride (cC.HCl) and arabinosylcytosine (araC) were compared. It was demonstrated that despite different... (Comparative Study)
Comparative Study
The basic biochemical characteristics of cyclocytidine hydrochloride (cC.HCl) and arabinosylcytosine (araC) were compared. It was demonstrated that despite different lipophilicity and different pK (4.15 for araC and 6.60 for cC.HCl), the mechanism of inhibition of DNA synthesis by both compounds is the same (ID50 for araC was 0.048 mumol/l and for cC. HCl 0.23 mumol/l). The compounds had a different mechanism of inhibition of RNA synthesis (ID50 for araC was 2.69 mmol/l and for cC.HCl 1.08 mmol/l) and showed a marginal effect on protein synthesis. Hydrolysis of the 0(2),2'-anhydro bond in cC.HCl and formation of araC in vivo was characterized by a Km = 280 mumol/l using HPLC. Deamination of araC in vivo was studied in healthy mice (Km = 247 mumol/l), 8.6% of arabinosyluracil 15 minutes after araC administration) and in mice with sensitive and araC resistant leukemia L1210 (15.5% and 8.5% of arabinosyluracil 15 minutes after araC administration, respectively). On the basis of different physico-chemical properties of cC.HCl and different mechanisms of inhibition of RNA synthesis it can be assumed that cC.HCl, when therapeutically used, may have its own mechanism of biological effect(s) and that its application may be therapeutically advantageous in some aspects as compared to araC.
Topics: Ancitabine; Animals; Cytarabine; DNA; Drug Resistance; Drug Stability; Female; Leukemia L1210; Male; Mice; Mice, Inbred DBA; Protein Biosynthesis; RNA; Tumor Cells, Cultured
PubMed: 1690864
DOI: No ID Found -
Cancer Dec 1989The authors treated 30 patients ages 1 to 19 with relapsed or refractory acute non-lymphoblastic leukemia (ANLL) with the combination of diaziquone (AZQ) and...
The authors treated 30 patients ages 1 to 19 with relapsed or refractory acute non-lymphoblastic leukemia (ANLL) with the combination of diaziquone (AZQ) and 2,2'-anhydro-arabinosyl-5-fluorocytosine (AAFC) intravenously in two dose schedules. The first 12 patients were treated with 19 courses of AZQ 30 mg/m2 X 3 days and AAFC 600 mg/m2/dose every 12 hours X 10 doses. An additional patient was treated with three courses at 80% of the above doses. Hepatic toxicity was National Cancer Institute Grade III in eight of 22 and Grade IV in one of 22 courses. Infectious complications were severe in all patients, including responders. One patient achieved a complete remission and one a partial remission; the latter died with marrow aplasia after a second course. Altogether three patients developed profound aplasia and died before marrow recovery. The authors treated a second group of 17 patients with AZQ 22.5 mg/m2/day X 3 days and AAFC 450 mg/m2/dose every 12 hours X 10 doses. Three patients achieved a complete remission and one patient a partial remission for 3, 4, 9, and 9 months, respectively. The remainder had progressive disease or no response. All patients developed profound myelosuppression but no toxic deaths occurred. Hepatic toxicity was reduced. Therapy induced cytoreduction of bone marrow was determined by flow cytometry in ten patients; none of these patients responded during the interval studied. Although AZQ and AAFC are active in childhood ANLL with acceptable toxicity, the combination does not appear more active than AZQ used alone. Future studies should define the role of AZQ in combination with other agents.
Topics: Adolescent; Ancitabine; Antineoplastic Agents; Aziridines; Benzoquinones; Bone Marrow; Cell Survival; Child; Child, Preschool; Cytarabine; Drug Administration Schedule; Drug Evaluation; Female; Humans; Infant; Leukemia, Myeloid, Acute; Male
PubMed: 2479459
DOI: 10.1002/1097-0142(19891215)64:12<2416::aid-cncr2820641203>3.0.co;2-y -
Mikrobiologicheskii Zhurnal 1989The method of dot DNA-DNA hybridization was used to reveal the inhibition of the synthesis of the adenoviral DNA by 6-azacytidine, cyclocytidine and ribamidyl in the...
The method of dot DNA-DNA hybridization was used to reveal the inhibition of the synthesis of the adenoviral DNA by 6-azacytidine, cyclocytidine and ribamidyl in the adenovirus-infected cells Hep-2, a degree of which depended on the preparation concentration.
Topics: Adenoviridae Infections; Adenovirus Infections, Human; Ancitabine; Azacitidine; Cells, Cultured; DNA, Viral; Humans; Isomerism; Nucleic Acid Hybridization; Nucleosides; Ribavirin
PubMed: 2482929
DOI: No ID Found