Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cascade testing”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed1999

Trophic cascades in a complex terrestrial community.

To test for direct and indirect effects of a top predator on three lower trophic levels, we conducted two multiyear predator addition experiments in a tropical wet forest. Periodic additions of a top predator (predatory clerid beetle) to a wet forest understory shrub caused a reduction in the predatory beetle's prey (a predatory ant), increased herbivory, and reduced leaf area of the plant. These effects occurred whether beetles were added to naturally occurring shrubs or to reproductive fragments, suggesting fitness effects of top predators through three trophic levels. A correlational study showed that trophic effects of top predators also cascaded to nearby conspecifics in the forest understory. We use trends from understory plant surveys to suggest mechanisms by which these cascades could ultimately affect species diversity in the local plant community.

Journal Article↗
PubMed1998

Transit compartments versus gamma distribution function to model signal transduction processes in pharmacodynamics.

Delayed effects for pharmacodynamic responses can be observed for many signal transduction processes. Three approaches are summarized in this report to describe such effects caused by cascading steps: stochastic process model, gamma distribution function, and transit compartment model. The gamma distribution function, a probability density function of the waiting time for the final step in a stochastic process model, is a function of time with two variables: number of compartments N, and the expected number of compartments occurring per unit time k. The parameter k is equal to 1/tau, where tau is the mean transit time in the stochastic process model. Effects of N and k on the gamma distribution function were examined. The transit compartment model can link the pharmacokinetic profile of the tested compound, receptor occupancy, and cascade steps for the signal transduction process. Time delays are described by numbers of steps, the mean transit time tau, and the amplification or suppression of the process as characterized by a power coefficient gamma. The effects of N, tau, and gamma on signal transduction profiles are shown. The gamma distribution function can be utilized to estimate N and k values when the final response profile is available, but it is less flexible than transit compartments when dose-response relationships, receptor dynamics, and efficiency of the transduction process are of concern. The transit compartment model is useful in pharmacokinetic/pharmacodynamic modeling to describe precursor/product relationships in signal transduction process.

Animals↗
PubMed2003

Characteristics of EPI-hNE4 aerosol: a new elastase inhibitor for treatment of cystic fibrosis.

The purpose of this study was to define nebulization conditions providing delivery of aerosols of EPI-hNE4, an inhibitor of human neutrophil elastase (HNE). EPI-hNE4 was nebulized with Pari LC Star and tested at three concentrations (2.5, 5, and 10 mg/mL). The inhaled mass was measured over 15 min. Particle size distribution was measured by cascade impaction. The effect was also tested of mixing EPI-hNE4 with a (99m)Tc human serum albumin (HSA) tracer on the aerodynamic properties of the aerosol. The inhibitory activity of EPI-hNE4 after nebulization was assessed on purified HNE. The inhaled mass was 32.3 +/- 3.5% (mean +/- SD) after 10 min and 44.2 +/- 3.8% (mean +/- SD) after 15 min. Mass median aerodynamic diameter ranged between 1.2 and 1.8 microm. The (99m)Tc HSA EPI-hNE4 aerosol was similar in terms of particle size distribution (y = 1.0338x - 0.003, r = 0.83). (99m)Tc activity was predictive of EPI-hNE4 mass distribution (y = 1.0278x - 1.6991, r = 0.89). The inhibitory capacity of aerosolized samples remained unchanged after up to 10 min of nebulization. EPI-hNE4 can be nebulized efficiently without decrease in its activity. Mixing this inhibitor with (99m)Tc HSA should allow quantification of its deposition in CF patients.

Administration, Inhalation↗
PubMed1999

Insulin stimulates ecdysteroid production through a conserved signaling cascade in the mosquito Aedes aegypti.

Selective activators and inhibitors of insulin signaling cascades in mammalian cells were tested for their effects on insulin stimulated steroidogenesis by ovaries of Aedes aegypti. Bovine insulin in the concentration range of 1.7 microM to 85 microM stimulated ecdysteroidogenesis in vitro. Pervanadate, an inhibitor of tyrosine kinase phosphatase, stimulated ecdysteroid production at concentrations of 250 microM to 1 microM. Okidaic acid, a serine/threonine phosphatase inhibitor, stimulated steroidogenesis with an ED50 of 77.39 nM. A selective inhibitor of tyrosine kinase activity, HNMPA-(AM3), inhibited ecdysteroid production with an IC50 of 14.2 microM. Two selective inhibitors of phosphatidylinositol 3-kinase, wortmannin and LY294002, inhibited ecdysteroid production at low concentrations (IC50 = 1.6 nM and 30 nM, respectively). These concentrations are similar to those inhibiting insulin action in mammalian cells. A selective inhibitor of mitogen-activated protein kinase, PD098059, had no effect on ecdysteroid production even up to 100 microM. Thus, insulin stimulation of ecdysteroid production by ovaries in vitro appears to be controlled by the tyrosine kinase activity of the mosquito insulin receptor and the signaling cascade involving phosphatidylinositol 3-kinase and protein kinase B.

Aedes↗
PubMed2005

Relationship of stage mensuration data to the performance of new and used cascade impactors.

Cascade impaction is a standard test method for characterizing the quality of inhalable drug products. The sizes of the nozzles on each stage of the impactor are the critical dimensions for the performance of the impactor. Compendial reference methods call for periodic measurement of the size of the nozzles on each stage, a procedure known as stage mensuration. There is however currently no guidance on acceptable mensuration criteria. We aim to remedy this situation by providing a sound basis for understanding and using mensuration data, be it for acceptance criteria for new impactors or for the setting of mensuration tolerances for in-use impactors. We first show that multi-nozzle impactor stages behave as if all of the nozzles are equal in size to an effective diameter, , that is composed of the area-mean and areamedian diameters, W* and , calculated directly from the individual nozzle diameters for all nozzles on a given stage (equation 1): W= (W*)(2/3) x (W)(1/3) (1). Hence, the effective diameter provides an intuitive and technically sound basis for setting acceptance criteria for new and in-use impactors. We tabulate these criteria for the Mark II eight-stage Andersen cascade impactor and the Next Generation Pharmaceutical Impactor in a manner similar to the tables of critical impactor dimensions published in EP Supplement 5.1 and in USP 28. For two different impactors or for one impactor measured at two different times (e.g., at manufacture and in use), we find that the D50 values of a given stage are related to the effective diameters by D(50,2)/D(50,1)= (W(2)/W(1))(3/2) (2). Using the stage mensuration data for new, as-manufactured NGIs, we compare the D(50 )values of the first 125 as-manufactured NGIs with those of the archivally calibrated NGI. We further establish that the archivally calibrated NGI has D(50) values within 0.3% of an entirely perfect, hypothetical NGI with all nozzles equal to the nominal nozzle diameters. We also apply the equations to a specific mensurated impactor to show that a used impactor with some nozzles outside of the original manufacturing specifications can have the same aerodynamic performance as a new impactor.

Aerosols↗
PubMed2005

Reverse cascade screening of newborns for hereditary haemochromatosis: a model for other late onset diseases?

BACKGROUND: Genetic testing can determine those at risk for hereditary haemochromatosis (HH) caused by HFE mutations before the onset of symptoms. However, there is no optimum screening strategy, mainly owing to the variable penetrance in those who are homozygous for the HFE Cys282Tyr (C282Y) mutation. The objective of this study was to identify the majority of individuals at serious risk of developing HFE haemochromatosis before they developed life threatening complications. METHODS: We first estimated the therapeutic penetrance of the C282Y mutation in people living in la Somme, France, using genetic, demographic, biochemical, and follow up data. We examined the benefits of neonatal screening on the basis of increased risk to relatives of newborns carrying one or two copies of the C282Y mutation. Between 1999 and 2002, we screened 7038 newborns from two maternity hospitals in the north of France for the C282Y and His63Asp (H63D) mutations in the HFE gene, using bloodspots collected on Guthrie cards. Family studies and genetic counselling were undertaken, based on the results of the baby's genotype. FINDINGS: In la Somme, we found that 24% of the adults homozygous for the C282Y mutation required at least 5 g iron to be removed to restore normal iron parameters (that is, the therapeutic penetrance). In the reverse cascade screening study, we identified 19 C282Y homozygotes (1/370), 491 heterozygotes (1/14) and 166 compound heterozygotes (1/42) in 7038 newborns tested. The reverse cascade screening strategy resulted in 80 adults being screened for both mutations. We identified 10 previously unknown C282Y homozygotes of whom six (four men and two women) required venesection. Acceptance of neonatal screening was high; parents understood the risks of having HH and the benefits of early detection, but a number of parents were reluctant to take the test themselves. Neonatal screening for HH is straightforward. Reverse cascade screening increased the efficiency of detecting affected adults with undiagnosed haemochromatosis. This strategy allows almost complete coverage for HH and could be a model for efficient screening for other late onset genetic diseases.

Adult↗
PubMed1998

Comparison of beta-protein/A4 deposits and Alz-50-stained cytoskeletal changes in the hypothalamus and adjoining areas of Alzheimer's disease patients: amorphic plaques and cytoskeletal changes occur independently.

Alzheimer's disease is characterized neuropathologically by senile plaques and cytoskeletal changes. It has been proposed that amorphic plaques would locally induce anterograde propagation of cytoskeletal changes in consecutive neurons followed by amorphic plaque deposition at their axonal terminals. The Alzheimer changes would spread in this way along neural pathways. To test the 'primary amyloid anatomical cascade hypothesis', Congo red staining, beta-protein/A4 (Abeta) antiserum and Alz-50, which recognizes cytoskeletal changes, were applied to the hypothalamus and adjoining brain areas of five Alzheimer's disease patients of 40-90 years of age and five age- and sex-matched controls. The results showed that (1) virtually all Abeta plaques in the hypothalamus were of the Congo red-negative amorphic type; (2) amorphic plaques and Alz-50-stained cytokeletal changes were observed not only in all Alzheimer's disease patients but also in a non-demented, 90-year-old control subject; (3) the density of amorphic plaques in the hypothalamus was unrelated to the duration of the dementia; (4) the density of amorphic plaques was unrelated to that of Alz-50-stained cytoskeletal changes; (5) double-labeling with anti-Abeta and Alz-50 did not show an evident topical relationship between amorphic plaque deposition and the occurrence of cytoskeletal changes; and (6) the distribution of Abeta and Alz-50 staining in five brain areas, for which essential anatomical information is available, did not support the primary amyloid anatomical cascade hypothesis. Amorphic plaques and cytoskeletal changes rather occur independently.

Adult↗
PubMedDate not supplied

Brain aging in the canine: a diet enriched in antioxidants reduces cognitive dysfunction.

Animal models that simulate various aspects of human brain aging are an essential step in the development of interventions to manage cognitive dysfunction in the elderly. Over the past several years we have been studying cognition and neuropathology in the aged-canine (dog). Like humans, canines naturally accumulate deposits of beta-amyloid (Abeta) in the brain with age. Further, canines and humans share the same Abeta sequence and also first show deposits of the longer Abeta1-42 species followed by the deposition of Abeta1-40. Aged canines like humans also show increased oxidative damage. As a function of age, canines show impaired learning and memory on tasks similar to those used in aged primates and humans. The extent of Abeta deposition correlates with the severity of cognitive dysfunction in canines. To test the hypothesis that a cascade of mechanisms centered on oxidative damage and Abeta results in cognitive dysfunction we have evaluated the cognitive effects of an antioxidant diet in aged canines. The diet resulted in a significant improvement in the ability of aged but not young animals to acquire progressively more difficult learning tasks (e.g. oddity discrimination learning). The canine represent a higher animal model to study the earliest declines in the cognitive continuum that includes age associated memory impairments (AAMI) and mild cognitive impairment (MCI) observed in human aging. Thus, studies in the canine model suggest that oxidative damage impairs cognitive function and that antioxidant treatment can result in significant improvements, supporting the need for further human studies.

Aging↗
PubMed2002

Predicting the quality of powders for inhalation from surface energy and area.

PURPOSE: To correlate the surface energy of active and carrier components in an aerosol powder to in vitro performance of a passive dry powder inhaler. METHODS: Inverse gas chromatography (IGC) was used to assess the surface energy of active (albuterol and ipratropium bromide) and carrier (lactose monohydrate, trehalose dihydrate and mannitol) components of a dry powder inhaler formulation. Blends (1%w/w) of drug and carrier were prepared and evaluated for dry powder inhaler performance by cascade impaction. The formulations were tested with either of two passive dry powder inhalers, Rotahaler (GlaxoSmithKline) or Handihaler (Boehringer Ingelheim). RESULTS: In vitro performance of the powder blends was strongly correlated to surface energy interaction between active and carrier components. Plotting fine particle fraction vs. surface energy interaction yielded an R2 value of 0.9283. Increasing surface energy interaction between drug and carrier resulted in greater fine particle fraction of drug. CONCLUSIONS: A convincing relationship, potentially useful for rapid formulation design and screening, was found between the surface energy and area parameters derived from IGC and dry powder inhaler performance.

Administration, Inhalation↗
PubMed2006

Phellinus linteus sensitises apoptosis induced by doxorubicin in prostate cancer.

It has been demonstrated that the Phellinus linteus (PL) mushroom, which mainly consists of polysaccharides, possesses antitumour activity. The mechanisms of PL against malignant growth remain unknown. The anticancer drug doxorubicin (Dox) has been shown to induce apoptosis via initiating a caspase cascade. In this investigation, we tested the effect of PL on Dox-induced apoptosis in prostate cancer LNCaP cells. We showed that PL or Dox, at relatively low doses, does not induce apoptosis in the cells. However, combination treatment with low doses of PL and Dox results in a synergistic effect on the induction of apoptosis. In this apoptotic process, caspases 8, 3 and BID are cleaved, and the addition of caspase inhibitor z-VADfmk completely blocks apoptosis. In addition, JNK is activated in response to PL or the combination treatment in LNCaP cells. The suppression of JNK partially inhibits the induction of apoptosis elicited by the co-treatment. These findings indicate that PL has a synergistic effect with Dox to activate caspases in prostate cancer LNCaP cells. Our study also suggests that PL has therapeutic potential to augment the magnitude of apoptosis induced by antiprostate cancer drugs.

Agaricales↗
PubMed2000

Tumor-suppressive effects by adenovirus-mediated mda-7 gene transfer in non-small cell lung cancer cell in vitro.

The melanoma differentiation-associated gene-7 (mda-7), cloned from a human melanoma cell line H0-1, is known to induce tumor cell-selective growth inhibition in breast cancer cells in vitro and loss of tumorigenicity ex vivo. Yet, the mechanisms underlying these effects are still unknown. Therefore, we investigated these mechanisms on the molecular level in human non-small cell lung carcinoma (NSCLC) cells in vitro. Overexpression of mda-7 protein by Ad-mda-7 significantly suppressed proliferation and induced G2/M cell cycle arrest in wild-type p53 (A549, H460), and p53-null (H1299) non-small cell lung cancer cell lines, but not in normal human lung fibroblast (NHLF) cells. p53, Bax, and Bak protein expression was up-regulated in wild-type p53 tumor cell lines, but not in p53-null cells, suggesting that an intact p53 pathway was required for Bax and Bak induction. However, in all three cancer cell lines tested, activation of the caspase cascade and cleavage of poly(ADP-ribose) polymerase (PARP) appeared to be independent of the p53 mutational status. Together, these results suggest that apoptosis may be induced via multiple pathways by Ad-mda-7 in lung cancer cells and that Ad-mda-7 has the potential to become a novel therapeutic for clinical cancer gene therapy. Gene Therapy (2000) 7, 2051-2057.

Adenoviridae↗
PubMed2003

[New aspects in pain research at Bayer].

Considerable advances in the fields of molecular biology and pain research during the last decade has led to the identification of a wide range of pharmacological targets for new analgesics. Genes of interesting targets may be regulated either upwards or downwards under pathophysiological, i. e. inflammatory or neuropathic pain conditions. Targets exclusively expressed in terms of tissues relevant for pain transmission, are potential promising candidates for the generation of analgesics devoid of serious side-effects. Especially those targets that are expected to be essential for the development and maintenance of a number of pains offer the opportunity to define courses of treatment for patients with a variety of different symptoms and causes. Modern drug-development is based on the identification of compounds directed against these specific targets. In a high throughput screening procedure, all substances of our drug library (about 1 million) are examined for their effects on this specific molecular mechanism. Predicted pain-relieving effects are then identified by a screening cascade where selected drugs are tested for their activity in in-vitro assays on isolated neurons, tissues or recombinant cell lines. The final validation of a drugs' antihyperalgetic or antiallodynic properties is carried out in the relevant animal models of chronic pain, which mirror the clinical situation as much as possible. Compounds being more efficient or having an improved side effect profile in these models than medications currently available (and which are toxicologically harmless) are interesting candidates for clinical development.

Acute Disease↗
PubMed1988

Evidence for extracellular, but not intracellular, generation of angiotensin II in the rat adrenal zona glomerulosa.

Based on the observation that high levels of renin and angiotensin II (Ang II) are found in the adrenal zona glomerulosa (ZG), it has been postulated that Ang II is formed intracellularly by the renin-converting enzyme cascade in this tissue. To test this hypothesis, we examined renin-angiotensin system components in subcellular fractions of the rat adrenal ZG. Renin activity and immunoreactive-Ang II (IR-Ang II) were observed in vesicular fractions but were not colocalized. In addition, angiotensinogen, angiotensin I, and converting enzyme were not observed in the renin or IR-Ang II-containing vesicular fractions. These data do not support the hypothesis that Ang II is formed intracellularly within the renin-containing vesicles of the ZG. Rather, since modulatable renin release from adrenal ZG slices was observed and renin activity was found in dense vesicular fractions (33-39% sucrose), it is likely that Ang II formation in the ZG is extracellular and initiated by the release of vesicular renin. Receptor-mediated endocytosis and subsequent degradation of Ang II in ZG lysosomes have been shown by others. The presence of IR-Ang II in light vesicular fractions (15% sucrose) and the finding of a high correlation between ZG IR-Ang II and Ang II receptor levels suggest that the primary occurrence of this peptide in the ZG is by receptor-mediated endocytosis. In ZG lysosomal fractions 125I-labeled Ang II was degraded to 125I-labeled des-[Phe8]Ang II. Since Ang II antibodies do not recognize des-[Phe8]Ang II, these findings explain why IR-Ang II in the ZG is due predominantly to Ang II and not to its C-terminal immunoreactive fragments.

Adrenal Cortex↗
PubMed2000

Functional expression of O-linked GlcNAc transferase. Domain structure and substrate specificity.

O-GlcNAc transferase (OGT) modifies nuclear pore proteins and transcription factors. In Arabidopsis, the OGT homolog participates in the gibberellin signaling pathway. We and others have proposed that mammalian OGT is the terminal step in a glucose-sensitive signal transduction pathway that becomes disregulated in insulin resistance. To facilitate mutational analysis of OGT in the absence of competing endogenous activity, we expressed the 103-kDa human OGT in Escherichia coli. Kinetic parameters for the purified recombinant enzyme (K(m) = 1.2 microM for Nup 62; K(m) = 0.5 microM for UDP-GlcNAc) are nearly identical to purified mammalian OGT. Deletions in the highly conserved C terminus result in a complete loss of activity. The N-terminal tetratricopeptide repeat domain is required for optimal recognition of substrates. Removal of the first three tetratricopeptide repeats greatly reduces the O-GlcNAc addition to macromolecular substrates. However, this altered enzyme retains full activity against appropriate synthetic peptides. Autoglycosylation of OGT is augmented when the first six tetratricopeptide repeats are removed showing that these repeats are not required for catalysis. Given its proposed role in modulating insulin action, OGT may modify kinases involved in this signaling cascade. Among the many kinases tested, OGT glycosylates glycogen synthase kinase-3 and casein kinase II, two enzymes critical in the regulation of glycogen synthesis.

Casein Kinase II↗
PubMed2006

ERK1/2 activation mediates Abeta oligomer-induced neurotoxicity via caspase-3 activation and tau cleavage in rat organotypic hippocampal slice cultures.

In this study, we investigated the molecular basis for the altered signal transduction associated with soluble amyloid beta-protein (Abeta) oligomer-mediated neurotoxicity in the hippocampus, which is primarily linked to cognitive dysfunction in Alzheimer disease (AD). As measured by media lactate dehydrogenase levels, and staining with propidium iodide, acute exposure to low micromolar concentrations of the Abeta1-42 oligomer significantly induced cell death. This was accompanied by activation of the ERK1/2 signal transduction pathway in rat organotypic hippocampal slices. Notably, this resulted in caspase-3 activation by a process that led to proteolytic cleavage of Tau, which was recently confirmed to occur in AD brains. Tau cleavage likely occurred in the absence of overt synaptic loss, as suggested by the preserved levels of synaptophysin, a presynaptic marker. Moreover, among the pharmacological agents tested to inhibit several kinase cascades, only the ERK inhibitor significantly attenuated Abeta1-42 oligomer-induced toxicity concomitant with the reduction of activation of ERK1/2 and caspase-3 to a lesser extent. Importantly, the caspase-3 inhibitor also decreased Abeta oligomer-induced cell death, with no appreciable effect on the ERK signaling pathway, although such treatment was effective in reducing caspase-3 activation and Tau cleavage. Therefore, these results suggest that local targeting of the ERK1/2 signaling pathway to reduce Tau cleavage, as occurs with the inhibition of caspase-3 activation, may modulate the neurotoxic effects of soluble Abeta oligomer in the hippocampus and provide the rationale for symptomatic treatment of AD.

Alzheimer Disease↗
PubMed2002

Effect of cage vs. floor litter environments on the pulmonary hypertensive response to intravenous endotoxin and on blood-gas values in broilers.

Intravenous endotoxin has been shown to trigger a delayed pulmonary hypertensive response that varies widely in magnitude and duration among individual broilers. It was proposed that this individual variability may reflect immunological differences acquired during previous respiratory challenges that might have subsequently altered the endotoxin-initiated biochemical cascade. In Experiment 1, we tested the hypothesis that, when compared with broilers reared in clean stainless steel cages (Cage group), broilers reared on floor litter (Floor group) should experience a greater respiratory challenge and therefore may consistently exhibit a more enhanced pulmonary hypertensive response to intravenous endotoxin. Birds in the Cage group were grown in stainless steel cages at a low density (72 birds/8 m2 chamber), and fecal and dander materials were removed daily. Birds in the Floor group were reared on wood-shavings litter at a higher density (110 birds/8 m2 chamber). Pulmonary and systemic mean arterial pressures and blood-gas values were evaluated prior to and following the intravenous administration of 1 mg Salmonella typhimurium endotoxin. Broilers in the Floor and Cage groups exhibited pulmonary hypertensive responses to endotoxin that were very similar in terms of time of onset, duration, and magnitude, as well as variability in the response among individuals. Systemic hypotension also developed similarly in both groups following endotoxin injection. Blood-gas values indicated that the partial pressure of CO2 and the HCO3- concentration in arterial blood were higher (P < 0.05) in the Floor group than in the Cage group prior to and subsequent to the endotoxin injection. In Experiment 2, we reevaluated the effect of a dirty vs. a clean environment on blood-gas values using a different strain of broilers, and confirmed the negative impact of floor rearing on blood-gas values. We conclude that broilers reared on the floor inhaled litter dust and noxious fumes, which impaired pulmonary gas exchange and increased the arterial partial pressure of CO2 when compared with broilers reared in clean stainless steel cages. Nevertheless, the pulmonary hypertensive response to endotoxin did not differ between broilers reared on the floor and those in cages.

Animal Husbandry↗
PubMed2005

Taxotere-5'-deoxy-5-fluorouridine combination on hormone-refractory human prostate cancer cells.

Single-agent docetaxel (Taxotere) treatment has recently demonstrated promising clinical activity in patients with advanced hormone-refractory prostate cancer. Taxanes were recently found to upregulate the tumoral activity of thymidine phosphorylase (TP), a key cellular enzyme [transformation of 5'-deoxy-5-fluorouridine (5'-DFUR) into 5-fluorouracil] in the activation cascade of capecitabine (Xeloda). We tested (cytotoxic effects and molecular mechanisms) the Taxotere-5'-DFUR combination on hormone-refractory prostate cancer cell lines (DU145 and PC3). Cells were exposed to Taxotere and/or 5'-DFUR in three different sequences: Taxotere was given alone for 48 h, then 5'-DFUR was added for 48 h; Taxotere and 5'-DFUR together during 96 h or 5'-DFUR was given alone for 48 h then Taxotere was added for 48 h. The drug sequence Taxotere applied first followed by 5'-DFUR led to synergistic cytotoxic effects on both cell lines; the other sequences resulted in simple additivity. Taxotere did not modify TP activity while it decreased thymidylate synthase activity. There was an increase in CD95 cellular membrane levels following exposure to Taxotere-5'-DFUR, which is in agreement with the supra-additive cytotoxic combination. This observation may serve as a preclinical rationale for a next step testing the Taxotere-capecitabine combination at the clinical level in prostate cancer patients.

Antineoplastic Agents, Phytogenic↗