Biomedical subjects

Ming Zhao

Publications and source records attributed to Ming Zhao.

At least 55 records · Page 3Linked to original sources

PubMed2006

[Short-term curative efficacy of cytokine-induced killer cells combined micro-invasive treatments on hepatocellular carcinoma].

BACKGROUND & OBJECTIVE: Recently, micro-invasive treatments showed well application prospective in treating primary hepatocellular carcinoma (HCC), while tumor immunotherapy is a hot topic in tumor treatment. This study was to investigate the efficacy of cytokine-induced killer cells (CIK) combined micro-invasive treatments (transcatheter arterial chemoembolization and radiofrequency ablation) on the recurrence of HCC. METHODS: A total of 85 HCC patients without active lesions and metastasis, which were displayed by imaging examination after transcatheter arterial chemoembolization and radiofrequency ablation therapy, were divided randomly into 2 groups: 45 in study group, and 40 in control group. The patients in study group were transfused with CIK cells through hepatic artery after micro-invasive treatments, while the patients in control group were not. The levels of T lymphocyte subsets and native killer (NK) cells in peripheral blood of HCC patients before and after CIK cell transfusion were detected by flow cytometry (FCM). Tumor condition was observed by CT scanning every 2-3 months. RESULTS: The percentages of CD3+, CD4+, and CD56+ effect cells and the proportion of CD4+/CD8+ were increased from (68.6+/-11.0)%, (31.0+/-9.0)%, (15.6+/-7.8)%, and 1.1+/-0.5 to (70.7+/-10.1)% (P<0.05), (33.5+/-8.0)% (P<0.05), (18.4+/-9.4)% (P<0.05), and 1.3+/-0.6 (P<0.05) after CIK cell transfusion; while the percentages of CD8+ and CD3+ CD56+ cells were decreased from (31.1+/-7.8)% and (6.4+/-3.5)% to (28.6+/-8.3)% (P<0.05) and (5.2+/-3.3)% (P<0.05). The 1- and 1.5-year recurrence rates were 8.89% and 15.56% in study group, and 30.00% and 40.00% in control group (Chi(2) = 4.87 and 6.41, P <0.05). CONCLUSION: CIK cell transfusion after micro-invasive treatments may improve the immunologic function in HCC patients, and play an important role in reducing the recurrence rate of HCC.

Adult↗

PubMed2006

[Detection of serum interleukin-6 level in patients with multiple myeloma of Vighur nationality and Han nationality and its clinical significance].

To investigate the difference of serum interleukin-6 level in the patients with multiple myeloma (MM) of Vighur nationality and Han nationality and its clinical significance, the activity of serum interleukin-6 was detected in 80 patients with MM (33 Vighur patients, 47 Han patients) and 30 normal subjects as control by using sandwich ELISA with double antibody. The results showed that there was significant difference in serum interleukin-6 level between Vighur patients and Han patients (P < 0.01). The serum interleukin-6 level of patients with multiple myeloma was significantly higher than that of nomal control (P < 0.01). The serum interleukin-6 level of MM patients in second and third stage were also signifivantly higher than that of patients in first stage (P < 0.05). It is concluded that there was significant difference in the serum interleukin-6 level between Vighur patients and Han patients. The serum interleukin-6 level can be considered as one of indexes to judge the patient severity and the prognosis, also as one of comprehensive multiparameters to evaluate the curative efficiency and guide the clinical application of drugs.

Adult↗

PubMed2005

In vitro and in vivo clinical pharmacology of dimethyl benzoylphenylurea, a novel oral tubulin-interactive agent.

Dimethyl benzoylphenylurea (BPU) is a novel tubulin-interactive agent with poor and highly variable oral bioavailability. In a phase I clinical trial of BPU, higher plasma exposure to BPU and metabolites was observed in patients who experienced dose-limiting toxicity. The elucidation of the clinical pharmacology of BPU was sought. BPU, monomethylBPU, and aminoBPU were metabolized by human liver microsomes. Studies with cDNA-expressed human cytochrome P450 enzymes revealed that BPU was metabolized predominantly by CYP3A4 and CYP1A1 but was also a substrate for CYP2C8, CYP2D6, CYP3A5, and CYP3A7. BPU was not a substrate for the efflux transporter ABCG2. Using simultaneous high-performance liquid chromatography/diode array and tandem mass spectrometry detection, we identified six metabolites in human liver microsomes, plasma, or urine: monomethylBPU, aminoBPU, G280, G308, G322, and G373. In patient urine, aminoBPU, G280, G308, and G322 collectively represented <2% of the given BPU dose. G280, G308, G322, and G373 showed minimal cytotoxicity. When BPU was given p.o. to mice in the presence and absence of the CYP3A and ABCG2 inhibitor, ritonavir, there was an increase in BPU plasma exposure and decrease in metabolite exposure but no overall change in cumulative exposure to BPU and the cytotoxic metabolites. Thus, we conclude that (a) CYP3A4 and CYP1A1 are the predominant cytochrome P450 enzymes that catalyze BPU metabolism, (b) BPU is metabolized to two cytotoxic and four noncytotoxic metabolites, and (c) ritonavir inhibits BPU metabolism to improve the systemic exposure to BPU without altering cumulative exposure to BPU and the cytotoxic metabolites.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2005

Feasibility of quantitative PCR-based saliva rinse screening of HPV for head and neck cancer.

Human papilloma virus (HPV) 16 is likely to be an etiologic factor in a subset of head and neck squamous cell carcinomas (HNSC). We investigated the ability of a quantitative PCR-based assay to detect HPV 16 in salivary rinses as a screening method for HNSC. Real time quantitative PCR was applied to detect HPV16 E6 and E7 DNA level in 92 primary tumors and salivary rinses from patients with HNSC and 604 control subjects without HNSC. A total of 45.6% (42/92) of primary HNSC and 32.6% (30/92) of saliva rinse samples from HNSC patients had any detectable HPV 16 DNA, 30.4% (28/92) of tumors had HPV 16 levels >0.1 copies/cell. HPV16 was detected in 50% (confidence interval [CI] = 34.2-65.8%) (21/42) of the saliva rinse samples from HNSC patients with detectable HPV16 level in their tissue, 18% (CI = 8.4-30.9%) (9/50) of saliva rinse samples from patients with HPV 16 negative primary HNSC, in 2.8% (CI = 1.7-4.5%) (17/604) of the normal controls (p < 0.001). Using a cutoff of HPV 16 >0.001 copies/cell in saliva rinse yielded a sensitivity of 30.4% and a specificity of 98.3%. Nonsmokers had significant higher HPV 16 level than smokers in the cohort of cancer patients. HPV 16 DNA in saliva rinses can reflect HPV 16 status of primary HNSC. Quantitative analysis of HPV 16 DNA in salivary rinses allows for detection of HPV-related HNSC, however, specific limitations exist that prevent the application of this as a screening technique for a broad population.

Adolescent↗

PubMed2005

Enhanced synchronizability by structural perturbations.

In this Brief Report, we investigate the collective synchronization of a system of coupled oscillators on a Barabási-Albert scale-free network. We propose an approach of structural perturbations aiming at those nodes with maximal betweenness. This method can markedly enhance the network synchronizability, and is easy to realize. The simulation results show that the eigenratio will sharply decrease by one-half when only 0.6% of those hub nodes occur under three-division processes when the network size . In addition, the present study also provides numerical evidence that the maximal betweenness plays a major role in network synchronization.

Journal Article↗

PubMed2005

Stereoselective synthesis and anti-inflammatory activities of 6- and 7-membered dioxacycloalkanes.

A class of 5-trifluoroacetylamino-1,3-dioxacycloalkanes, 5-benzoylamino-1,3-dioxacycloalkanes, and 5-amino-1,3-dioxacycloalkane compounds were stereoselectively synthesized as potential anti-inflammatory drug candidates. The anti-inflammatory activities of these compounds were tested using the xylene-induced mouse ear edema model, from which multiple compounds possessing anti-inflammatory properties which surpass aspirin were identified; these compounds were then compared to establish structure-activity relationships.

Animals↗

PubMed2005

Head and neck cancer cell lines exhibit differential mitochondrial repair deficiency in response to 4NQO.

Constituents of tobacco can cause DNA adduct formation and are implicated in head and neck squamous cell cancer (HNSC) development. We investigated the capacity of HNSC cell lines to repair mitochondrial DNA (mtDNA) damage induced by a DNA adduct-forming agent. HNSC cell lines underwent 4-nitroquinoline 1-oxide (4NQO) exposure with subsequent rescue with normal media. Real-time quantitative PCR for nuclear DNA (nDNA) and mtDNA was performed. mtDNA to nDNA ratios were calculated and standardized to mock-treated cells to assess mtDNA repair ability. Two of three tested cancer cell lines exposed to 4NQO exhibited consistent decreases in mtDNA/nDNA ratios throughout the different repair timepoints. At 24 h mtDNA/nDNA ratios of JHU-O19 and JHU-O22 decreased to 63% and 60% of controls, respectively. Conversely, a control keratinocyte cell line exhibited overall increases in mtDNA/nDNA ratios compared to baseline suggesting intact DNA repair mechanisms. By using a DNA adduct formation and repair model featuring 4NQO and HNSC cell lines, we have implicated faulty mtDNA repair as having a potential role in HNSC.

4-Nitroquinoline-1-oxide↗

PubMed2005

Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan.

PURPOSE: Milk thistle (Silybum marianum) is one of the most commonly used herbal therapies, and its principal constituent silybin significantly inhibits cytochrome P450 isoform 3A4 (CYP3A4) and UDP glucuronosyltransferase isoform 1A1 (UGT1A1) in vitro. Here, we investigated whether milk thistle affects the pharmacokinetics of irinotecan, a substrate for CYP3A4 and UGT1A1, in humans. EXPERIMENTAL DESIGN: Six cancer patients were treated with irinotecan (dose, 125 mg/m(2)) given as a 90-minute infusion once every week. Four days before the second dose, patients received 200 mg milk thistle, thrice a day, for 14 consecutive days. Pharmacokinetic studies of irinotecan and its metabolites 7-ethyl-10-hydroxycamptothecin (SN-38), 7-ethyl-10-[3,4,5-trihydroxy-pyran-2-carboxylic acid]-camptothecin (SN-38-glucuronide), and 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin were done during the first three irinotecan administrations. RESULTS: Short-term (4 days) or more prolonged intake of milk thistle (12 days) had no significant effect on irinotecan clearance (mean, 31.2 versus 25.4 versus 25.6 L/h; P = 0.16). The area under the curve ratio of SN-38 and irinotecan was slightly decreased by milk thistle (2.58% versus 2.23% versus 2.17%; P = 0.047), whereas the relative extent of glucuronidation of SN-38 was similar (10.8 versus 13.5 versus 13.1; P = 0.64). Likewise, the area under the curve ratio of 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin and irinotecan was unaffected by milk thistle (0.332 versus 0.285 versus 0.337; P = 0.53). The maximum plasma concentrations of silybin ranged between 0.0249 and 0.257 micromol/L. CONCLUSIONS: Silybin concentrations after intake of milk thistle are too low to significantly affect the function of CYP3A4 and UGT1A1 in vivo, indicating that milk thistle is unlikely to alter the disposition of anticancer drugs metabolized by these enzymes.

Adolescent↗

PubMed2005

Validation and implementation of a liquid chromatography/tandem mass spectrometry assay to quantitate dimethyl benzoylphenylurea (BPU) and its five metabolites in human plasma and urine for clinical pharmacology studies.

A method has been developed for the quantitation of N-[4-(5-bromo-2-pyrimidinyloxy)-3-methylphenyl]-N'-(2-dimethylamino-benzoyl)urea (BPU) and its metabolites in human plasma and urine. BPU and metabolites were separated on a C18 column with acetonitrile-water mobile phase containing 0.1% formic acid using isocratic flow for 5 min. The analytes were monitored by tandem mass spectrometry. Calibration curves were generated over the range of 2.5-500 ng/mL for BPU, mmBPU, and aminoBPU in plasma; and 0.1-20, 0.1-20, 0.5-100, 10-2000, 1-200, and 3-600 ng/mL for BPU, mmBPU, aminoBPU, G280, G308, and G322 in urine, respectively. The method has been successfully applied to study the pharmacokinetics of BPU.

Calibration↗

PubMed2005

Regulation of CXCR4-mediated nuclear translocation of extracellular signal-related kinases 1 and 2.

Activation of the chemokine receptor CXCR4 by its agonist stromal cell-derived factor 1 (SDF-1) has been associated with cell migration and proliferation in many cell types, but the intracellular signaling cascades are incompletely defined. Here we show that CXCR4-dependent extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation was mediated through the Ras/Raf pathway, as demonstrated with a dominant-negative Ras mutant and pharmacological inhibitors. The Src inhibitor 4-amino-5-methylphenyl-7-(t-butyl)pyrazolo[3,4-d] pyrimidine (PP1) and the Rho-kinase (ROCK) inhibitor N-(4-pyridyl)-4-(1-aminoethyl)cyclohexanecarboxamide dihydrochloride (Y27632) also attenuated SDF-1-induced ERK1/2 phosphorylation. Involvement of Src could furthermore be demonstrated by Src phosphorylation and by the shortened ERK1/2 phosphorylation in SYF cells, which are Src/Yes/Fyn-deficient compared with Src-reconstituted Src(++) cells. Membrane translocation of RhoA could be detected similarly. A large portion of the SDF-1-mediated ERK phosphorylation was detected in the nucleus, as shown by Western blotting and confocal microscopy, and resulted in the phosphorylation of the transcription factor Elk. It is interesting that the nuclear accumulation of ERK1/2 and Elk phosphorylation was completely blocked by dominant-negative Rho, Y27632, PP1, and latrunculin B, indicating that the Rho/ROCK pathway, Src kinase, and the actin cytoskeleton were required in this process. In accordance, neither nuclear ERK phosphorylation nor Elk phosphorylation were observed in SYF cells stimulated with SDF-1 but were reconstituted in Src(++) cells. In summary, these results demonstrate that Src, Rho/ROCK, and an intact cytoskeleton contribute to overall ERK1/2 activation in SDF-1-stimulated cells and are indispensable for nuclear translocation of ERK1/2 and activation of transcription factors.

Actins↗

PubMed2005

Novel synthesis and anti-inflammatory activities of 2,5-disubstituted-dioxacycloalkanes.

A novel stereospecific synthetic route to obtain a series of 2,5-disubstituted-dioxacycloalkanes is reported. Using an in vivo inhibition assay by monitoring xylene-induced ear edema in mice, the structure-activity relationship of the dioxacycloalkane compounds was studied, and compounds possessing high anti-inflammatory activity were identified.

Animals↗

PubMed2005

Reciprocal binding of CTCF and BORIS to the NY-ESO-1 promoter coincides with derepression of this cancer-testis gene in lung cancer cells.

Regulatory sequences recognized by the unique pair of paralogous factors, CTCF and BORIS, have been implicated in epigenetic regulation of imprinting and X chromosome inactivation. Lung cancers exhibit genome-wide demethylation associated with derepression of a specific class of genes encoding cancer-testis (CT) antigens such as NY-ESO-1. CT genes are normally expressed in BORIS-positive male germ cells deficient in CTCF and meCpG contents, but are strictly silenced in somatic cells. The present study was undertaken to ascertain if aberrant activation of BORIS contributes to derepression of NY-ESO-1 during pulmonary carcinogenesis. Preliminary experiments indicated that NY-ESO-1 expression coincided with derepression of BORIS in cultured lung cancer cells. Quantitative reverse transcription-PCR analysis revealed robust, coincident induction of BORIS and NY-ESO-1 expression in lung cancer cells, but not normal human bronchial epithelial cells following 5-aza-2'-deoxycytidine (5-azadC), Depsipeptide FK228 (DP), or sequential 5-azadC/DP exposure under clinically relevant conditions. Bisulfite sequencing, methylation-specific PCR, and chromatin immunoprecipitation (ChIP) experiments showed that induction of BORIS coincided with direct modulation of chromatin structure within a CpG island in the 5'-flanking noncoding region of this gene. Cotransfection experiments using promoter-reporter constructs confirmed that BORIS modulates NY-ESO-1 expression in lung cancer cells. Gel shift and ChIP experiments revealed a novel CTCF/BORIS-binding site in the NY-ESO-1 promoter, which unlike such sites in the H19-imprinting control region and X chromosome, is insensitive to CpG methylation in vitro. In vivo occupancy of this site by CTCF was associated with silencing of the NY-ESO-1 promoter, whereas switching from CTCF to BORIS occupancy coincided with derepression of NY-ESO-1. Collectively, these data indicate that reciprocal binding of CTCF and BORIS to the NY-ESO-1 promoter mediates epigenetic regulation of this CT gene in lung cancer cells, and suggest that induction of BORIS may be a novel strategy to augment immunogenicity of pulmonary carcinomas.

Antigens, Neoplasm↗

PubMed2005

Comparison of TCDD and PCB CYP1A induction sensitivities in fresh hepatocytes from human donors, sprague-dawley rats, and rhesus monkeys and HepG2 cells.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related chemicals induce cytochrome P450 1A (CYP1A) gene expression and, at sufficient exposures, cause toxicity. Human health risks from such exposures are typically estimated from animal studies. We tested whether animal models predict human sensitivity by characterizing CYP1A gene expression in cultures of fresh hepatocytes from human donors, rats, and rhesus monkeys and HepG2 human hepatoma cells. We exposed the cells to three aryl hydrocarbon receptor (AhR) ligands of current environmental interest and measured 7-ethoxyresorufin-O-deethylase (EROD) activity and concentrations of CYP1A1 and CYP1A2 mRNA. We found that human cells are about 10-1000 times less sensitive to TCDD, 3,3',4,4',5-pentachlorobiphenyl (PCB 126), and Aroclor 1254 than rat and monkey cells, that relative potencies among these chemicals are different across species, and that gene expression thresholds exist for these chemicals. Newly calculated rat-human interspecies relative potency factors for PCB 126 were more than 100 times lower than the current rodent-derived value. We propose that human-derived values be used to improve the accuracy of estimates of human health risks.

Animals↗

PubMed2005

Synthesis and biological activity of nitronyl nitroxide containing peptides.

[1-(1',3'-Dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetic acid (4), a nitronyl nitroxide, and its peptide derivatives, N-[1-(1',3'-dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetyl-ARPAK (9a), -GRPAK (9b), and -QRPAK (9c), were synthesized and characterized. Judging from the results of electron spin resonance analysis, the newly synthesized nitronyl nitroxide containing peptides, 9a, 9b, and 9c, demonstrated the characteristics of free radicals. The free radical scavenging activities of 9a, 9b, and 9c were assessed using in vitro free radical scavenging tests. The thrombolysis effect of 9a, 9b, and 9cwas evaluated using an euglobulin clot lysis test, a fibrinolytic lysis test, and in vivo thrombolysis tests. Results indicated that these nitronyl nitroxide containing peptides possessed both free radical scavenging activity and thrombolytic activity.

Amino Acid Sequence↗

PubMed2005

Stage-specific expression of dynein light chain-1 and its interacting kinase, p21-activated kinase-1, in rodent testes: implications in spermiogenesis.

Mammalian spermatogenesis is a complex process involving regulatory interactions of many gene products. In this study, we found that dynein light chain-1 (DLC1), a component of the dynein motor complex, is highly expressed in mouse and rat testes. Immunohistochemically detectable levels of DLC1 are observed specifically in spermatids in steps 9-16 in distinct subcellular compartments: in steps 9-11, DLC1 is predominantly localized in the nucleus; in steps 12 and 13, it is found in both nucleus and cytoplasm; and in step 14-16, it is present exclusively in the cytoplasm. In addition, we found p21-activated kinase 1 (Pak1), a protein kinase that activates DLC1 by phosphorylating DLC1 at Serine 88, was also expressed during these stages of spermatogenesis. Pak1 was also expressed in Leydig cells, in preleptotene primary spermatocytes, and in round spermatids. The spermiogenic stage-specific expression of DLC1 suggests a role for DLC1 in chromatin condensation, spermatid shaping, and the final release of sperm from the spermatogenic epithelium. Further, Pak1 may also play a role in spermiogenesis by regulating DLC1 phosphorylation and, consequently, its function.

Animals↗

PubMed2005

Specific method for determination of gefitinib in human plasma, mouse plasma and tissues using high performance liquid chromatography coupled to tandem mass spectrometry.

A rapid, sensitive and specific method was developed and validated using liquid chromatography-tandem mass spectrometry (LC/MS/MS) for determination of gefitinib in human plasma and mouse plasma and tissue. Sample preparation involved a single protein precipitation step by the addition of 0.1 mL of plasma or a 200 mg/mL tissue homogenate diluted 1/10 in human plasma with 0.3 mL acetonitrile. Separation of the compounds of interest, including the internal standard (d8)-gefitinib, was achieved on a Waters X-Terra C18 (50 mm x 2.1 mm i.d., 3.5 microm) analytical column using a mobile phase consisting of acetonitrile-water (70:30, v/v) containing 0.1% formic acid and isocratic flow at 0.15 mL/min for 3 min. The analytes were monitored by tandem mass spectrometry with electrospray positive ionization. Linear calibration curves were generated over the range of 1-1000 ng/mL for the human plasma samples and 5-1000 ng/mL for mouse plasma and tissue samples with values for the coefficient of determination of > 0.99. The values for both within- and between-day precision and accuracy were well within the generally accepted criteria for analytical methods (< 15%). This method was subsequently used to measure concentrations of gefitinib in mice following administration of a single dose of 150 mg/kg intraperitoneally and in cancer patients receiving an oral daily dose of 250 mg.

Animals↗

PubMed2005

Combinatorial gene therapy for bone regeneration: cooperative interactions between adenovirus vectors expressing bone morphogenetic proteins 2, 4, and 7.

Bone morphogenetic proteins (BMPs) have demonstrated effectiveness as bone regeneration agents whether delivered as recombinant proteins or via gene therapy. Current gene therapy approaches use vectors expressing single BMPs. In contrast, multiple BMPs are coordinately expressed during bone development and fracture healing. Furthermore, BMPs likely exist in vivo as heterodimeric molecules having enhanced biological activity. In the present study, we test the hypothesis that gene therapy-based bone regeneration can be enhanced by expressing combinations of BMPs. For in vitro studies, mesenchymal cell lines were transduced with individual adenoviruses containing BMP2, 4, or 7 cDNA under control of a CMV promoter (AdBMP2, 4, 7) or virus combinations. Significantly, combined transduction with AdBMP2 plus AdBMP7 or AdBMP4 plus AdBMP7 resulted in a synergistic stimulation of osteoblast differentiation. This synergy is best explained by formation of BMP2/7 and 4/7 heterodimers. To test in vivo biological activity, fibroblasts were transduced with specific virus combinations and implanted into C57BL6 mice. Consistent with in vitro results, strong synergy was observed using combined AdBMP2/BMP7 treatment, which induced twofold to threefold more bone than would be predicted based on the activity of individual AdBMPs. These studies show that dramatic enhancement of osteogenesis can be achieved using gene therapy to express specific combinations of interacting regenerative molecules.

Adenoviridae↗

PubMed2005

Pharmacokinetics of 5-azacitidine administered with phenylbutyrate in patients with refractory solid tumors or hematologic malignancies.

PURPOSE: To characterize the pharmacokinetic behavior of 5-azacitidine (5-AC), a cytidine nucleoside analog, when given with phenylbutyrate, a histone deaceytlase inhibitor. PATIENTS AND METHODS: Pharmacokinetic data were obtained from two trials involving patients with solid tumor and hematologic malignancies. 5-AC at doses ranging from 10 to 75 mg/m2/d was administered once daily as a subcutaneous injection for 5 to 21 days in combination with phenylbutyrate administered as a continuous intravenous infusion for varying dose and duration every 28 or 35 days. Serial plasma samples were collected up to 24 hours after 5-AC administration. 5-AC was quantitated using a validated liquid chromatograph/tandem mass spectrometry method. RESULTS: 5-AC was rapidly absorbed with the mean T(max) occurring at 0.47 hour. Average maximum concentration (C(max)) and area under the curve (AUC(0-infinity)) values increased in a dose-proportionate manner with increasing dose from 10 to 75 mg/m2/d; the mean +/- SD C(max) and AUC(0-infinity) at 10 mg/m2/d were 776 +/- 459 nM and 1,355 +/- 1,125 h*nM, respectively, and at 75 mg/m2/d were 4,871 +/- 1,398 nM and 6,582 +/- 2,560 h*nM, respectively. Despite a short terminal half-life of 1.5 +/- 2.3 hours, inhibition of DNA methyl transferase activity in tumors of patients receiving 5-AC has been documented. CONCLUSION: 5-AC is rapidly absorbed and eliminated when administered subcutaneously. Sufficient 5-AC exposure is achieved to produce pharmacodynamic effects in tumors.

Antimetabolites, Antineoplastic↗