Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cDNA fragment homologous to other G protein-coupled receptors was isolated from rat brain using the PCR method and demonstrated to be abundantly expressed in striatum. Using this fragment as a probe, a 2.1 kb full-length cDNA was isolated from a rat striatal cDNA library. This cDNA encodes a protein of 410 amino acids and is highly homologous to previously isolated adenosine receptor cDNAs. Expression of this cDNA in COS cells revealed high affinity (Kd = 38.6 nM) and saturable binding of the A2 adenosine receptor-selective ligand [3H]CGS 21680. Agonist displacement profile of [3H]CGS 21680 binding was consistent with an adenosine receptor of the A2 subtype (NECA greater than (R)-PIA greater than CPA greater than (S)-PIA). In situ hybridization demonstrated that rat A2 adenosine receptor mRNA was co-expressed in the same striatal neurons as D2 dopamine receptor mRNA, and never co-expressed with striatal D1 dopamine receptor mRNA. Several lines of evidence have previously suggested that dopamine-induced changes in motor behavior can be modulated by adenosine analogs acting at the A2 subtype of adenosine receptor in the forebrain. The co-expression of D2 dopamine and A2 adenosine receptors in a subset of striatal cells provides an anatomical basis for dopaminergic-adenosinergic interactions on motor behavior.
Brain Res Mol Brain Res 1992 Jul
PMID:Molecular cloning of the rat A2 adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum. 127 42

The effect of variations in experimental protocol on the assessment of the genotoxicity of 1,2-dimethylhydrazine (DMH) in the bone marrow micronucleus assay was determined. The incidence of micronuclei (MN) in the bone marrow of CBA mice treated with DMH (either intraperitoneally (i.p.) or orally) was found to be significantly greater than that observed in C57B1/6J mice using the same dose and dosing regimen. With i.p. injection, DMH, at doses of 20 and 50 mg/kg, was found to be positive in the bone marrow MN test in CBA mice only. In C57B1/6J mice, DMH (i.p.) was found to be positive at only the 50 mg/kg dose. With oral administration, DMH was positive in the MN test only at the 50 mg/kg dose and only in CBA mice. No significant difference in the percentage of MN was observed when 300, 500, or 1,000 polychromatic erythrocytes (PCEs) were scored following a single treatment of DMH. Cyclophosphamide (CY) was found to induce a dose-dependent increase in the percentage of MN observed in the bone marrow of C57B1/6J mice. DMH tested positive in the colon nuclear aberration (NA) assay in both strains of mice using both i.p. and oral routes of administration, although C57B1/6J mice were found to be more sensitive than CBA mice. No significant difference was observed regarding the percentage of NAs observed in the colon between mice injected i.p. or orally gavaged.
Environ Mol Mutagen 1991
PMID:Assessment of 1,2-dimethylhydrazine in bone marrow micronucleus assay: variations in protocol and response. 170 24

We have evaluated the effect of Interleukin-2 [IL-2] after Cyclophosphamide (C) chemotherapy in 41 patients with metastatic cancer. IL-2 was given as a continuous infusion priming cycle 36 hours after C at 1 gm/m2 intravenously. In 39 evaluable patients, there were no complete remissions [CR], 2 partial remissions [PR], and 1 had a minor response [MR]. Stable disease for 30 days was seen in 16 patients whereas 20 progressed. The durations of partial and minor responses were brief, ranging from 1-6 months. Grade 3-4 neutropenia was seen in 41%. This was more severe than seen with IL-2 alone or IL-2 combined with lower doses of C. The marrow suppression was due to the chemotherapy. This combination of IL-2 and C appears to be reasonably well tolerated by patients, but toxicity is greater and the response rate is no better than results achieved by IL-2 alone. Responses of 26 patients with renal cancer appear to be inferior to our historical data using IL-2/LAK cells without C. Immune monitoring demonstrated changes expected with C chemotherapy (i.e., a non-selective decline in immune function). C induced no further differences in IL-2 induced changes in immune function.
Mol Biother 1991 Jun
PMID:Continuous infusion of interleukin-2 and cyclophosphamide as treatment of advanced cancers: a National Biotherapy Study Group Trial. 191 Jun 23

We conducted a study to determine if treatment with cyclophosphamide (CY) could suppress the formation of anti-murine and anti-ricin A chain antibodies in rats treated with a murine monoclonal antibody-ricin A chain immunotoxin (IT). Female Sprague-Dawley rats received intravenous doses of IT at a dose of 5 mg/kg body weight alone or in combination with CY at a dose level of either 10 or 20 mg/kg body weight. The IT was given as one or two courses consisting of five consecutive daily intravenous injections (days 0 to 4, or days 0 to 4 and days 21 to 25 of the study). Cyclophosphamide was given on days 2, 4, 6, 13, and 17 of the study to the group receiving a single course of IT; additional doses of CY were administered on days 23, 25, and 27 to the group receiving two courses of IT. On days 4, 14, 21, 28, and 35, animals from each group were evaluated for antibodies to murine IgG and ricin A chain, and for clinical laboratory parameters and histopathology. Animals receiving IT alone developed significant titers of both anti-murine and anti-ricin A chain antibodies. Compared with the response in the animals receiving single-course IT, the response to both of the components of the IT was significantly increased on days 28 and 35 in the animals receiving a second course of IT. The groups receiving a combination of either one or two courses of CY and IT demonstrated a significantly decreased antibody response to both the murine IgG and the ricin A chain compared with the group receiving IT alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Biother 1990 Sep
PMID:The effects of cyclophosphamide on the toxicity and immunogenicity of ricin A chain immunotoxin in rats. 222 2

An Aroclor-induced rat hepatic S-9 metabolic activation system was incorporated into the BALB/3T3 cell transformation assay to increase its sensitivity to a wide range of procarcinogens. S-9 was prepared from Aroclor 1254-induced (500 mg/kg) Fischer 344 rats. Cyclophosphamide, dimethylnitrosamine, 2-aminofluorene, and 2-naphthylamine were metabolized to reactive forms capable of inducing both dose-dependent toxicity and morphological transformation of BALB/3T3 cells. Treatments without an exogenous metabolic activation system were nontoxic and nontransforming. Adaptation of this commonly used exogenous metabolic activation system to BALB/3T3 cells will allow detection of the transforming potential of procarcinogens which test negative in a standard assay.
Environ Mol Mutagen 1990
PMID:Morphological transformation of BALB/3T3 cells by various procarcinogens in the presence of a rat liver S-9 activation system. 225 7

We investigated whether estrogenic recruitment could enhance the antitumor effect of chemotherapy in 165 patients with advanced breast cancer, presumably sensitive to hormonal treatments (ER + and/or PgR + lesions). The therapeutic regimen consisted of: (a) estrogenic suppression by aminoglutethimide 1 g/day + hydrocortisone 40 mg/day; surgical castration in premenopausal patients only; (b) FAC (5FU 500 mg/m2; ADM 50 mg/m2; CPA 500 mg/m2) for 3 weeks; (c) following randomization, exactly 24 h prior to chemotherapy, patients had to take 1 tablet of either placebo (PL) or 50 microgram ethinylestradiol (EE2). Tolerance, responses, time to progression and median survival were identical in both groups. Thus, EE2 before chemotherapy did not contribute to the efficacy of this particular therapeutic regimen, which yielded an overall response rate of 64%. We conclude that the validity of the hormonal recruitment concept has not yet been established in clinical practice, so that this approach remains experimental.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Assessment of estrogenic recruitment before chemotherapy in advanced breast cancer: preliminary results of a double-blind randomized study of the EORTC Breast Cancer Cooperative Group. 228 84

A current hypothesis suggests that androgen administration prior to chemotherapy (androgen priming) may potentiate tumor cytotoxicity in prostate cancer. The Dunning R3327G rat prostatic tumor model was used to test this concept experimentally. Control groups without priming included (1) intact untreated, (2) castrate alone and (3) castrate+ chemotherapy (cyclophosphamide, 30 mg/kg/day for 2 days with repeat cycle in 25 days- CTX). Two experimental groups received androgens, one before and one after chemotherapy. Treatment effect was monitored by quantitating tumor volume and animal survival. Control groups receiving castration and chemotherapy had a retardation of tumor growth and a prolongation of survival when compared to untreated animals. Androgen priming before but not after chemotherapy enhanced the degree of tumor suppression. With the androgen-priming protocol, all androgen-primed tumors had regressed, 3/6 tumors had disappeared and 3 were only palpable. At the same time point, tumors in all the other groups were actively growing and had volumes greater than the initial values (P less than 0.01). Median survival was significantly prolonged in primed animals 191 vs 40 days for untreated animals and 150 days for the nonprimed castration + chemotherapy animals (P less than 0.02). These findings have been repeated with several replicate experiments. These observations confirm the hypothesis that androgen priming can potentiate chemotherapy in an experimental system.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Androgen-primed chemotherapy-experimental confirmation of efficacy. 228 85

Lonidamine (LND), previously reported as a useful antitumor substance in combination with physical or chemical agents, has been studied for its capacity in increasing pharmacological elimination in vitro of residual tumor cells from human bone marrow. Different drugs were tested in association with LND against mixtures of human bone marrow and a tumor cell line, clonogenic human leukemic blast progenitors, and normal human bone marrow precursors. The results demonstrated that LND increased the efficacy of anthracycline derivatives (Adriamycin, Mitoxantrone) both on the tumor cell line and on the leukemic blast progenitors, while VP-16 or ASTA-Z 7654 was not affected by the same substance. The toxicity on normal stem cells reflected that of each drug and was not modified by the addition of LND. While a consistent dose-dependent CFU-GM reduction was observed immediately after treatment with the different drugs, a complete recovery was reached after 7 and 14 days of long-term marrow cultures. Because of the low toxicity and the efficacy demonstrated in association with certain agents in increasing tumor cell elimination in vitro, LND could play an important role in in vitro purging prior to autologous bone marrow transplantation.
Exp Mol Pathol 1989 Apr
PMID:In vitro pharmacological purging of human bone marrow is enhanced by the use of lonidamine. 270 84

The influence of the natural polyamines [spermine (Sp) and spermidine (Spd)] on the conformation of thymus DNA molecule (M = 4 and 15 MDa) was studied by means of the viscometric method over the range of low supporting electrolyte concentrations (CNaCl = 0.6 divided by 8.4 mM). In was shown that at sufficiently low degrees of ligand binding (theta PA) which satisfy the condition ZPA theta PA less than 0.76 (where ZPA is the valence of PA), the PA addition results in a slight decrease of the volume effects in the DNA molecule due to the increase of the ionic strength (mu) of solution conditioned by the presence of polyvalent PA cations and also to the supplanting of "bound" Na+ cations. The further increase in CPA induces the corresponding increase in theta PA up to the value which provides ZPA theta PA greater than 0.76, and is accompanied by drastic decrease of macromolecule's dimensions and partial DNA condensation as well. At larger degrees of binding (ZPA theta PA approximately 0.90) a transition from the expanded to compact form of the DNA molecule is observed. The calculations of theta 1 = theta Na + theta PA and rcr = theta 1 + ZPA theta PA as a function of mu were carried out according to Manning's two-variables theory on the basis of the obtained dependences of the critical PA concentrations (Ccr PA), which correspond to the midpoint of the condensational transition, versus CNaCl. The increase of rcr and/or decrease of the effective site dimensions (ZPA) was shown to be necessary for the DNA molecule collapse over the range of low mu less than 0.01. The binding constants of the PA association to the compact DNA form were evaluated by the simplest model of McGhee and von Hippel. On the basis of the results obtained for Spd it was hypothesized that the non-electrostatic interactions are significant by the binding of the PA to the compact form of the DNA molecule.
Mol Biol (Mosk)
PMID:[Binding of polyamines by the double-helical DNA molecule in unfolded and compact forms]. 277 Jul 29

Cyclophosphamide was given intraperitoneally to groups of eight female mice 48 h after local electron irradiation to the bladder with 0, 10 and 20 Gy respectively. The reactions in the urothelium were monitored by histology, incorporation of tritiated thymidine and flow cytometry. A wave of increased thymidine incorporation combined with an increase in the proportion of diploid S-phase cells was seen in the unirradiated bladders 24 h after the drug treatment, followed by normalization after 1 week. This response was significantly less pronounced in the irradiated animals. In the unirradiated animals a similar wave characterized by an increased proportion of octaploid cells was also seen, but this wave occurred later in the irradiated animals. Severe injury was observed in the rectum of the 20 Gy-irradiated animals. Irradiation prior to drug treatment led to only small effects, but a decreased ability for regenerative DNA synthesis after drug injury seems to persist. This affects both proliferation and the building up of polyploidy.
Virchows Arch B Cell Pathol Incl Mol Pathol 1985
PMID:Some cell kinetic effects of combined injury with ionizing radiation and cyclophosphamide on mouse bladder urothelium. 286 33


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