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At least 937 records · Page 52Linked to original sources
PubMed1997

S-phase fraction, 5-bromo-2'-deoxy-uridine labelling index, duration of S-phase, potential doubling time, and DNA index in benign and malignant brain tumors.

Seventy-one histologically malignant brain tumors, 52 histologically benign brain tumors, and 14 cerebral metastases were characterized according to DNA content and proliferative capacity. DNA ploidy, DNA index (DI), S-phase fraction (SPF), 5-bromo-2'-deoxy-uridine (BrdUrd) labelling index (LI), duration of S-phase (Ts), and potential doubling time (Tpot) were assessed by flow cytometry (FCM). In histologically benign tumors, a high percentage of DNA diploid tumors and a low proliferative capacity in DNA diploid tumors were found. Histologically malignant tumors and cerebral metastases were both found to be characterized by a low percentage of DNA diploid tumors and a high proliferative capacity in DNA diploid tumors. The proliferative capacity of DNA aneuploid benign tumors and that of DNA aneuploid malignant tumors, however, appeared not to differ significantly. The number of DNA aneuploid tumors was small. Duration of S-phase was short (range 3.9-4.7 hr) and appeared not to differ between the three groups. From this, the observed differences in Tpot values should be accredited mainly to differences in LI. High-grade as well as low-grade gliomas both appeared to be characterized by malignant (FCM) features, i.e., 1) a high percentage DNA aneuploidy, 2) a high mean DI (for DI > 1), and 3) a high proliferative capacity.

Aneuploidy↗
PubMed2006

A phase II study of PS-341 (Bortezomib) in advanced or metastatic urothelial cancer. A trial of the Princess Margaret Hospital and University of Chicago phase II consortia.

BACKGROUND: Based on evidence of activity in epithelial tumors in preclinical and Phase I studies, its novel mechanism of action, and its tolerability we undertook a study of bortezomib [PS-341], a reversible proteasome inhibitor, for patients with advanced or metastatic urothelial cancer. PATIENTS AND METHODS: Patients with advanced or metastatic unresectable urothelial carcinoma were enrolled onto this multicenter, phase II trial. Patients with measurable disease were treated with bortezomib 1.3 mg/m2/day (twice weekly for 2 weeks out of 3) by intravenous infusion on days 1, 4, 8, and 11 every 21 days. A two stage phase II design was used. RESULTS: Twenty-one patients were enrolled and twenty were eligible and received treatment. Eighty-five percent of patients had previous chemotherapy regimens. No objective responses were observed, median time-to-progression was 8.1 weeks (95% confidence interval [CI] 6.4 to 9), and median overall survival is estimated to be 15 weeks (95% CI 3.6 - NA). A total of 15 patients experienced a grade 3-4 adverse event. The most common were alkaline phosphatase (20% patients), lymphopenia (20% patients), myalgia (15% patients), dyspnea (15% patients) and thrombosis/embolism (15% patients). CONCLUSION: Single-agent bortezomib is an ineffective treatment for progressive-cisplatin-refractory urothelial carcinoma and should not be considered for future clinical trials in this population of patients.

Aged↗
PubMed2006

Use of solid-phase microextraction to detect and quantify gas-phase dicarbonyls in indoor environments.

Solid-phase microextraction (SPME) was evaluated for the detection and quantification of the gas-phase dicarbonyls, glyoxal (GLY) and methylglyoxal (MGLY). Additionally, polydimethylsiloxane (PDMS), polydimethylsiloxane/divinylbenzene (PDMS/DVB), and carbowax/divinylbenzene (CW/DVB) fibers were tested to determine the optimum fiber for detection of these species. GLY and MGLY were derivatized with O-(2,3,4,5,6-pentafluorobenzyl)-hydroxylamine hydrochloride (PFBHA), extracted with SPME from headspace or bag chamber and then analyzed by GC/MS. The PDMS/DVB SPME fiber for on-fiber derivatization and subsequent sampling for gas-phase methylglyoxal provided the optimum combination of analytical reproducibility and sensitivity. Linearity of the calibration curve was achieved across a range of 11-222 microg/m(3) (4-75 ppb).

Air Pollutants↗
PubMed2003

Decitabine induces cell cycle arrest at the G1 phase via p21(WAF1) and the G2/M phase via the p38 MAP kinase pathway.

Methylation of the p16 (INK4a) tumor suppressor gene is observed frequently in multiple myeloma and various forms of lymphoma and mediates silencing of p16 gene expression. In this investigation, we have determined the effect of the DNA demethylating drug decitabine (DAC; 5-aza-2'-deoxycytidine) on the growth, cell cycle kinetics, RB phosphorylation, and expression of p16 (INK4a) and p21(WAF1) in EBV- human myeloma and EBV+ lymphoblastic cell lines possessing silenced, methylated p16 (INK4a) genes to: (1). evaluate its potential as a therapeutic agent and (2). investigate its mechanism of action. Demethylation of the p16 (INK4a) gene and expression of the p16 (INK4a) protein were observed using higher doses (10(-6)-10(-7)M) of drug while growth inhibition at lower doses (IC(50)=2 x 10(-8)-4 x 10(-8)M) was associated with RB dephosphorylation and increased expression of p21 (WAF1), but not with induction of p16 (INK4a), or apoptosis. Kinetic experiments demonstrated that RB dephosphorylation and the increase of p21 (WAF1) preceded the induction of p16 (INK4a). The drug induced cell cycle arrest at the G1 and G2/M phases. Antisense experiments demonstrated that the G1 arrest was mediated by transcriptional induction of p21(WAF1). In addition to these observed effects on cell cycle regulatory proteins, decitabine also increased phosphorylation of p38 MAP kinase. The G2/M arrest was inhibited by the p38 MAP kinase inhibitor SB203580, indicating that activation of p38 MAP kinase pathway was required for G2/M arrest. Thus, decitabine inhibited growth by inducing cell cycle arrest at the G1 phase mediated by p21(WAF1) and the G2/M phase through activation of the p38 MAP kinase pathway.

Antimetabolites, Antineoplastic↗
PubMed2004

Comparison study of the solution phase versus solid phase place exchange reactions in the controlled functionalization of gold nanoparticles.

Gold nanoparticles offer tremendous potential in the areas of nanoelectronics, bio- and chemosensors, and catalysis. However, before these applications are realized, the surface functionality of nanoparticles must be better controlled. Our lab has recently reported a novel synthetic approach for making monofunctionalized nanoparticles through a solid phase place exchange reaction. Monofunctionalized gold nanoparticles may also be prepared through a solution phase place exchange reaction. In this study, we compared the efficiency of these two separate approaches toward controlled functionalization of gold nanoparticles by (1)H NMR, Fourier transform infrared (FT-IR), and transmission electron microscopy (TEM) analysis. We found that the solid phase place exchange approach is much more efficient at producing monofunctionalized gold nanoparticles. (1)H NMR data were used to give a semiquantitative count of substituted bifunctional ligands, and FT-IR spectra supported these findings. Furthermore, we used a diamine coupling reaction of nanoparticles to show the presence of single or multiple functional groups on the nanoparticle surface by TEM analysis.

Diamines↗
PubMed1999

A sensitive docetaxel assay in plasma by solid-phase extraction and high performance liquid chromatography-UV detection: validation and suitability in phase I clinical trial pharmacokinetics.

We have developed a specific and sensitive method aiming at docetaxel (Taxotere) determination in plasma of treated patients. This involved solid-phase extraction of 1 ml of plasma onto carboxylic acid (CBA) grafted silica cartridges followed by reversed-phase liquid chromatography with UV detection. The best selectivity was obtained through the use of C18 Uptisphere as stationary phase. The low limit of quantitation obtained (LOQ: 5 ng/ml) allowed measurements of docetaxel up to 24 hours after one-hour infusions with low dosages of drug (60 mg/m2). The method was applied successfully to monitor docetaxel plasma levels within two protocols associating fixed dosages of either methotrexate or gemcitabine with escalating doses of Taxotere.

Antimetabolites, Antineoplastic↗
PubMed2004

Phase I clinical and pharmacokinetic study of BBR 3576, a novel aza-anthrapyrazole, administered i.v. every 4 weeks in patients with advanced solid tumors: a phase I study group trial of the Central European Society of Anticancer-Drug Research (CESAR).

BBR 3576 is a novel aza-anthrapyrazole with limited potential for cardiotoxicity in preclinical models. This phase I clinical and pharmacokinetic study was performed to determine the maximum tolerated dose, the dose-limiting toxicity (DLT) and the pharmacokinetic profile of BBR 3576 administered i.v. as a 1-h infusion repeated every 4 weeks. In total, 27 patients were treated at doses starting from 1 to 150 mg/m2. The dose levels 1, 2, 4, 8, 16, 32, 64, 90, 125 and 150 mg/m2 were investigated in one, three, one, three, two, one, three, four, three and six patients, respectively. The DLT was a grade 3 stomatitis at 150 mg/m2. At this dose level as well as at 125 mg/m2, neutropenia grade 3 and 4 were frequently seen, but not reaching the criteria for DLT. Time to neutrophil nadir was about 2 weeks and recovery took place within 1 week. Other bone marrow toxicities were mild; lymphopenia was also observed. No significant drug-induced cardiotoxicity was observed. The plasma concentration versus time curves of BBR 3576 showed a biexponential profile with a linear kinetic behavior. A very large volume of distribution, a high plasma clearance and long elimination half-lives were calculated. Renal unchanged drug excretion was less than 10% and therefore a minor excretion route. No objective antitumor responses were found. On the basis of this study, the recommended dose for phase II studies is 150 mg/m2, although the maximum tolerated dose as per protocol definition was not reached. This trial showed that BBR 3576 has a manageable toxicity profile on a 4-week schedule. Phase II studies have started in patients with solid tumors, as suggested by preclinical data in different in vivo model systems.

Adult↗
PubMed2004

Vascular segmentation of phase contrast magnetic resonance angiograms based on statistical mixture modeling and local phase coherence.

In this paper, we present an approach to segmenting the brain vasculature in phase contrast magnetic resonance angiography (PC-MRA). According to our prior work, we can describe the overall probability density function of a PC-MRA speed image as either a Maxwell-uniform (MU) or Maxwell-Gaussian-uniform (MGU) mixture model. An automatic mechanism based on Kullback-Leibler divergence is proposed for selecting between the MGU and MU models given a speed image volume. A coherence measure, namely local phase coherence (LPC), which incorporates information about the spatial relationships between neighboring flow vectors, is defined and shown to be more robust to noise than previously described coherence measures. A statistical measure from the speed images and the LPC measure from the phase images are combined in a probabilistic framework, based on the maximum a posteriori method and Markov random fields, to estimate the posterior probabilities of vessel and background for classification. It is shown that segmentation based on both measures gives a more accurate segmentation than using either speed or flow coherence information alone. The proposed method is tested on synthetic, flow phantom and clinical datasets. The results show that the method can segment normal vessels and vascular regions with relatively low flow rate and low signal-to-noise ratio, e.g., aneurysms and veins.

Algorithms↗
PubMed1992

Hysteroscopic assessment of midsecretory-phase endometrium, with special reference to the luteal-phase defect.

To investigate the functional aspects of secretory-phase endometrium, hysteroscopy was performed in 61 patients for in vitro fertilization-embryo transfer (IVF-ET), and 50 women for infertility evaluation. All women had normal ovulatory cycles. The hysteroscopic assessment of secretory-phase endometrium was made by characterizing the glandular openings (GO) and vasculature. The assessments were classified as 'good': characterized by ring-type GO and well-developed vessels; and 'poor': characterized by dot and/or punctate-type GO and fine vasculature. In the 30 patients classified 'good' prior to the IVF cycle, there was a higher pregnancy rate (40%) than in 'poor' ones (13%). Thirty of 50 infertile women were classified 'good', and their average age was lower than that of the remaining 20 in the 'poor' group. Preovulatory estradiol was significantly higher in the 'good' than in the 'poor' group. From an analysis of 20 patients with a 'poor' assessment, it was demonstrated that the maturation of secretory-phase endometrium was affected by a failure of folliculogenesis, progesterone secretion, endometrial growth and menstrual shedding.

Adult↗
PubMed1994

A human nuclear protein with sequence homology to a family of early S phase proteins is required for entry into S phase and for cell division.

Molecular cloning and characterisation of a human nuclear protein designated BM28 is reported. On the amino acid level this 892 amino acid protein, migrating on SDS-gels as a 125 kDa polypeptide, shares areas of significant similarity with a recently defined family of early S phase proteins. The members of this family, the Saccharomyces cerevisiae Mcm2p, Mcm3p, Cdc46p/Mcm5p, the Schizosaccharomyces pombe Cdc21p and the mouse protein P1 are considered to be involved in the onset of DNA replication. The highest similarity was found with Mcm2p (42% identity over the whole length and higher than 75% over a conservative region of 215 amino acid residues), suggesting that BM28 could represent the human homologue of the S. cerevisiae MCM2. Using antibodies raised against the recombinant BM28 the corresponding antigen was found to be localised in the nuclei of various mammalian cells. Microinjection of anti-BM28 antibody into synchronised mouse NIH3T3 or human HeLa cells presents evidence for the involvement of the protein in cell cycle progression. When injected in G1 phase the anti-BM28 antibody inhibits the onset of subsequent DNA synthesis as tested by the incorporation of bromodeoxyuridine. Microinjection during the S phase had no effect on DNA synthesis, but inhibits cell division. The data suggest that the nuclear protein BM28 is required for two events of the cell cycle, for the onset of DNA replication and for cell division.

3T3 Cells↗
PubMed1990

Luteal-phase defect induced by deprivation of FSH at a specific period of the follicular phase prevents pregnancy in the bonnet monkey (Macaca radiata).

Female bonnet monkeys were injected i.v. with 25 microliters antiserum to FSH on Days 5, 6 or 7 of the cycle: the length of the luteal phase was shortened but there was no alteration in cycle length. Proven fertile females (N = 6) were caged throughout the period of the experiment (6 cycles) with proven fertile males and treated with 25 microliters FSH antiserum on Day 7 of each of 3 successive cycles. Out of 18 cycle exposures during the treatment phase, 17 were ovulatory, but no pregnancies occurred. In the post-treatment phase, 5 monkeys became pregnant within 3 cycle exposures. These results show that it is possible to render female monkeys infertile by creating luteal insufficiency and this can be achieved repeatedly in a reproducible manner by depriving the cyclic females of FSH support on Day 7 of consecutive cycles.

Animals↗
PubMed2000

[Phase II trial evaluating the effect of megestrol acetate-prednisolone combination in the treatment of anorexia during the palliative-care phase of lung cancer].

OBJECTIVES: Anorexia is one of the most frequent complaints in patients who have reached the palliative-care phase of lung cancer. Megestrol acetate (or medroxyprogesterone acetate) and corticosteroids have been used with success, but the effect of their combination remains unknown. We conducted a phase II trial to assess the impact of combination therapy. PATIENTS AND METHODS: Patients with lung cancer given palliative care and who developed anorexia with or without weight loss were given 320 mg/d megestrol acetate in 2 doses and 40 mg/d prednisolone in one dose in the morning for 1 month. The principal outcome criterion was anorexia assessed on a visual analog scale prior to treatment and then at day 15 and day 30. Variation in daily calorie intake and weight were also recorded. We used an Armitage sequential plan to determine the number of inclusions necessary and the preference method (closed schema) to evaluate the principal outcome criterion. RESULTS: Inclusions were stopped after the eighth patient (giving p<0.05) as we observed a significant improvement in patient appetite. Daily calorie intake improved significantly (p<0.0001), by 39.18% the first 15 days and 16.57% more the next 15 days. Body weight improved significantly by 5.4% in one month (p=0.5). No treatment-related complication occurred during the study period or during the six consecutive months. CONCLUSIONS: The megestrol acetate-prednisolone combination was found to improve anorexia in patients with lung cancer in the palliative-care phase and allowed a significant improvement in calorie intake and body weight.

Adult↗
PubMed1995

Expression of a deletion mutant of the E2F1 transcription factor in fibroblasts lengthens S phase and increases sensitivity to S phase-specific toxins.

To better understand how the E2F1 transcription factor contributes to the process of cell proliferation, NIH-3T3 cell lines were generated that constitutively express either the wild-type E2F1 protein or an amino terminal deletion mutant, termed E2F1d87. Proliferating E2F1d87-expressing cells exhibit a significant lengthening of S phase relative to control and E2F1 cell lines and are hypersensitive to the cytotoxic effects of the S phase-specific antitumor drug camptothecin. This sensitivity is associated with an increase in drug-induced p53 and WAF1 levels. The E2F1 and E2F1d87 cell lines are both able to initiate, but not complete, S phase under conditions of serum starvation. However, quantitation of DNA synthesis, during culture in serum-deprived media, indicates that the E2F1d87 cell line synthesizes more DNA/cell as compared to the E2F1 cell line. Consistent with this relative increase in DNA synthesis, the E2F1d87 cell line undergoes camptothecin-induced apoptosis when cultured under conditions of serum starvation, while the control and E2F1 cell lines are unaffected by drug treatment under the same conditions. Thus, the sensitivity of the E2F1d87 cell line to camptothecin is not dependent on cell proliferation. The data presented here suggest that cell cycle parameters can be manipulated in order to enhance sensitivity of a cell to the toxic effects of specific chemotherapeutic agents.

3T3 Cells↗
PubMedDate not supplied

The kil gene of the ColE1 plasmid of Escherichia coli controlled by a growth-phase-dependent promoter mediates the secretion of a heterologous periplasmic protein during the stationary phase.

Heterologous gene products produced by Escherichia coli cells can be exported into the culture medium by the action of the kil gene of the ColE1 plasmid, which encodes a bacterial release protein. The kil gene was fused with the stationary-phase promoter of the fic gene of E. coli, and a secretion cassette (Kil-Km cassette) containing the regulated kil gene, the Km-resistance gene, and multiple cloning sites for the integration of target genes was constructed. Using the gene for beta-glucanase (bgl) as a target gene, it was shown that the protein produced was only secreted into the medium during the stationary phase. Quasi-lysis and lethality were not observed. The primary effect of the induction of the kil gene was the overproduction of beta-glucanase. The total amount produced per milliliter of bacterial culture was almost threefold higher than that of the corresponding Kil- control. The protein pattern of periplasm and culture medium was analyzed before and after induction of the kil gene expression, indicating that the release of periplasmic proteins is semiselective. This secretion system is the first to use a growth-phase-regulated promoter for the expression of the kil gene.

Bacterial Proteins↗
PubMed1998

The acute phase reaction syndrome: the acute phase reactants (a review).

The acute phase reaction of the organism, which determines the response that follows the injury of tissues and organs and helps the survival of the individual is reviewed. The main participants, the induction of the reaction and the regulatory mechanisms are shortly discussed, with special respect to the prominent role of interleukin-6. The relationship between the production and synthesis of the acute phase reactants under physiological and pathophysiological conditions is analyzed. The particular functions of orosomucoid and alpha 2HS-glycoprotein are summarized. Finally, the common biological actions of IL-6 and the acute phase reactants are mentioned.

Acute-Phase Reaction↗
PubMed1996

Differences in colocalization between Fos and PHI, GRP, VIP and VP in neurons of the rat suprachiasmatic nucleus after a light stimulus during the phase delay versus the phase advance period of the night.

Two groups of four rats each received a 15-minute light stimulus during the first part of the night (ZT14) and the second part (ZT19), respectively. After 45-60 minutes, the animals were killed by perfusion fixation. Adjacent Vibratome sections through the suprachiasmatic nucleus (SCN) were double-immunostained for the presence of peptide histidine isoleucine (PHI), gastrin releasing peptide (GRP) or vasoactive intestinal peptide (VIP) with Fos by using fluorophore-conjugated secondary antibodies. A few sections were triple-immunostained for PHI, GRP or VIP with vasopressin (VP) and Fos. Sections were analyzed with a confocal laser scanning microscope. It turned out that the ZT19 light stimulus induced 4.2 times more nuclear profiles in the SCN immunoreactive for Fos than the light stimulus given at ZT14. The SCN of control animals did not show any Fos immunoreactivity. After the ZT14 light stimulus, approximately 33% of the Fos profiles showed colocalization with a perikaryal profile immunoreactive for PHI, GRP or VIP, whereas at ZT19, this percentage had doubled to approximately 65%. After the light stimulus at ZT14, the relatively low Fos induction was numerically and proportionally most prominent in the PHI-immunoreactive perikarya. As compared with ZT14, the increase of Fos after the ZT19 light stimulus was most pronounced in the GRP-immunoreactive perikarya (21x) followed by VIP (15x) and PHI (5x). This outcome suggests that at least three different cell groups characterized by, respectively, PHI alone, GRP, and VIP fully or partly colocalized with PHI, play a prominent role during light-induced phase shifts: the PHI neurons during light-induced phase delays, the GRP and VIP/(PHI) neurons during light-induced phase advances.

Animals↗
PubMed2000

Estimating disease prevalence from two-phase surveys with non-response at the second phase.

In this paper we compare several methods for estimating population disease prevalence from data collected by two-phase sampling when there is non-response at the second phase. The traditional weighting type estimator requires the missing completely at random assumption and may yield biased estimates if the assumption does not hold. We review two approaches and propose one new approach to adjust for non-response assuming that the non-response depends on a set of covariates collected at the first phase: an adjusted weighting type estimator using estimated response probability from a response model; a modelling type estimator using predicted disease probability from a disease model; and a regression type estimator combining the adjusted weighting type estimator and the modelling type estimator. These estimators are illustrated using data from an Alzheimer's disease study in two populations.

Black or African American↗
PubMed2002

Structure and phase stability of binary zintl-phase compounds: lithium-group 13 intermetallics and metal-doped group 14 clathrate compounds.

The structure/bonding relationship in a series of intermetallic phases of Li with Al, Ga, and In was investigated by density functional theory and complemented by a model based on tight-binding theory and the method of moments. The combination of these two approaches provides a simple scheme which allows for both a comprehensive understanding of structural trends and the ability to predict low-energy structures for a given composition. This analysis gives a straightforward picture of phase stability in terms of local geometric features such as triangular, square, and hexagonal arrangements of atoms. The approach was extended to examine the structural properties of metal-doped clathrate compounds of C, Si, Ge, and Sn. Clathrate-type phases based on the frameworks Si172, Ge172, Si40, and Ge40 are not only likely to be energetically favorable but may also exhibit high thermoelectric efficiency.

Journal Article↗