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Biomedical subjects

J Chang

Publications and source records attributed to J Chang.

At least 307 records · Page 17Linked to original sources
PubMed1996

Twin studies demonstrate a host cell genetic effect on productive human immunodeficiency virus infection of human monocytes and macrophages in vitro.

Biological and genetic variability is a prominent feature of human immunodeficiency virus (HIV) strains, especially in tropism, syncytium formation, and replicative capacity. To determine whether there were variable host cell effects on HIV replication in monocytes, three different strains of low-passage-number monocytotropic blood isolates of HIV and the laboratory-adapted strain Ba-L were inoculated into panels of adherent monocytes drawn from 44 different donors, and peak extracellular HIV p24 antigen titers were compared. The clinical HIV strains showed patterns of either moderate or low-level replication in most donor monocytes (20 to 4,000 pg/ml). However, within this range there was marked variation in peak titers in most donors. HIV type 1 Ba-L replicated in all donor monocytes to much higher levels with less variability (30 to 40 ng/ml). Furthermore, replication of 21 clinical blood-derived strains of HIV in blood monocytes and monocyte-derived macrophages (MDM) from pairs of identical twins and age-matched unrelated donors (URD) of the same sex were compared. In all of the seven pairs of identical twins, the kinetics of replication (measured by extracellular HIV p24 antigen) of panels of four clinical HIV type 1 isolates in monocytes were similar within pairs. However, marked and significant differences in kinetics of HIV production occurred within 10 of the 12 unrelated donor pairs (P = 0.0007). The remaining two URD pairs showed similar kinetic patterns, but only one pair had the same HLA-DR genotype. Similar results were observed with monocytes/MDMs obtained from a second bleed of the same donor. Hence, discordant patterns of HIV replication kinetics between URD monocyte pairs contrasted with concordant patterns in identical twin monocytes. These data strongly suggest a host cell genetic effect on productive viral replication in monocytes and MDMs. So far, no consistent genetic linkage of HIV replication pattern with HLA-DR genotype has been observed.

Adult↗
PubMed1996

Nitric oxide donor prevents hydrogen peroxide-mediated endothelial cell injury.

Because nitric oxide is being used to treat acute lung injury and because it may either reduce or potentiate oxidant-mediated vascular injury, we studied the effect of the nitric oxide donor S-nitroso-N-acetyl-D-penicillamine (SNAP) on hydrogen peroxide (H2O2)-induced injury to cultured rat lung microvascular endothelial cells (RLMVC). Cells were exposed to H2O2 through its enzymatic generation by glucose and glucose oxidase or by its direct application. Glucose oxidase exposure causes a concentration- and time-dependent increase in 51chromium (51Cr) release from RLMVC. Catalase, dimethylthiourea or deferoxamine protects against this oxidant injury. SNAP (100 microM) prevents the increase in 51Cr release resulting from glucose oxidase or direct application of H2O2. N-acetyl-D-penicillamine is ineffective. Photo-decayed SNAP slightly decreases the 51Cr release caused by glucose oxidase but not the injury produced by directly adding H2O2. Treatment with the guanosine 3',5'-cyclic monophosphate (cGMP) analogue 8-BrcGMP (1-10 mM) provides no protection. SNAP decreases in vitro the net oxidation of ferrous to fcrric iron by H2O2, the iron-catalyzed consumption of H2O2 in Fenton's reaction, the iron-mediated generation of hydroxyl radicals, and the Fe(2+)-H2O2-catalyzed peroxidation of lipid membranes. Providing exogenous nitric oxide dramatically prevents H2O2-mediated endothelial injury, likely by reducing iron-mediated oxidant generation and subsequent lipid peroxidation.

Animals↗
PubMed1996

Shear stress alters pleural mesothelial cell permeability in culture.

The sliding motion of the lung against the chest wall creates a shear stress in the pleural space, which can be as high as 60 dyn/cm2, depending on the respiration rate. Such shear stresses may affect the mesothelial cells that line the pleural space on the lung (visceral pleura) and chest wall (parietal pleura). When exposed to shear stress (17 dyn/cm2) in a parallel-plate flow chamber for 22 h, rat visceral pleura mesothelial cells were not altered morphologically and did not align in the direction of flow, in contrast to the shape changes observed for bovine aortic endothelial cells. By using mesothelial cells cultured on porous microcarrier beads, we measured the permeability of the cells at different flows in a cell-column chromatography assay. The permeabilities to sodium fluorescein and cyanocobalamin increased from 8.2 +/- 1.0 and 7.8 +/- 0.7 x 10(-5) cm/s to 22.5 +/- 1.2 and 21.8 +/- 3.0 x 10(-5) cm/s, respectively, when the flow was increased from 0.9 to 3.5 ml/min (corresponding to average shear stresses of 4.7-18.4 dyn/cm2). The permeabilities returned to baseline values when the flow was reduced. Cytochalasin D stimulated an increase in permeability that was not augmented by a subsequent increase in shear stress. These results suggest that the barrier function of mesothelial cells is responsive to changes in fluid shear stress.

Animals↗
PubMed1996

Primary brain tumor incidence rates in four United States regions, 1985-1989: a pilot study.

There has been controversy in the last decade over whether the reported increase in brain tumors reflects a real increase in incidence rates. Incidence data on the full spectrum of brain tumors is lacking in the discussion since current cancer reports in the United States are restricted to malignant tumors. Data on tumors from four population-based cancer registries in the United States were compiled to provide incidence rates of benign and malignant brain tumors and to assess the feasibility of providing these data on a larger scale. A total of 8,070 primary tumors diagnosed from 1985 to 1989 in Connecticut, Massachusetts, Missouri and Utah were obtained. Brain tumors were defined using the International Classification of Diseases for Oncology codes 191.0-191.9, 192.0-192.3, 192.8-192.9 and 194.3-194.4. Stratum-specific incidence rates by location and histology were estimated by sex, age and region. Age-adjusted rates were standardized to the 1970 United States population. An age-adjusted incidence rate of 9.4/10(5) was observed, which reflects a 36% increase in males and a 68% increase in females over the rate based on malignant tumors alone from the Surveillance, Epidemiology and End Results cancer reporting system. Incorporating benign tumors into cancer registry data would increase the reported incidence rates primarily in females and for meningiomas and nerve sheath tumors. This expanded incidence rate represents a substantial improvement in the ability to describe the occurrence of these complex tumors by subtype with a modest increase in overall case registrations for cancer registries. Centralization of data on all brain tumors appears feasible. Variations in histology-specific rates across regions raises questions that need to be addressed about the ascertainment and accuracy of tumor classification. Use of the cancer registration system to improve the reporting of brain tumors in the United States is important to our understanding of the occurrence of these complex tumors and to our ability to conduct large-scale epidemiologic investigations.

Adolescent↗
PubMed1996

Stimulation of cilia beat frequency by serotonin is mediated by a Ca2+ influx in ciliated cells of Helisoma trivolvis embryos

Serotonin (5-HT) has been established as a regulator of ciliary beating in numerous systems. In early embryos of Helisoma trivolvis, a cilia-driven rotational movement is modulated by the release of endogenous serotonin from a pair of embryonic neurons, ENC1s, directly onto the ciliated epithelium. The present study was undertaken to examine the signal transduction mechanisms underlying serotonin-mediated cilio-excitation in Helisoma trivolvis embryos. Using time-lapse videomicroscopy, the ciliary beat frequency (CBF) of cultured embryonic ciliated cells was measured in response to various pharmacological manipulations. Serotonin increased CBF in a dose-dependent manner. Addition of 8-bromo-cyclic AMP, isobutylmethylxanthine (IBMX) or a combination of forskolin and IBMX, treatments that elevate the concentration of intracellular cyclic AMP, did not mimic the serotonin-induced increase in CBF. Thus, cyclic AMP does not appear to be involved in the regulation of CBF in this system. In contrast, depolarizing the cells with KCl or veratridine, and artificially raising the intracellular Ca2+ concentration with thapsigargin or A23187, caused a serotonin-like increase in CBF. Furthermore, the serotonin response was abolished in a Ca2+-depleted medium or in a medium containing the L-type Ca2+ channel blockers verapamil or nifedipine. These results suggest that serotonin-stimulated cilio-excitation in cultured Helisoma trivolvis cells involves an influx of Ca2+ to increase intracellular Ca2+ concentration. The link between serotonin-receptor binding and Ca2+ influx in these cells has yet to be determined.

Journal Article↗
PubMed1996

Comparative sensitivities and specificities of the mass measurements of CK-MB2, CK-MB, and myoglobin for diagnosing acute myocardial infarction.

We evaluated the clinical utility of the mass measurement of the tissue isoform of creatine kinase MB isoenzyme (CK-MB2) in the diagnosis of an acute myocardial infarction (AMI) by determining its sensitivity, specificity, and predictive value relative to those of CK-MB mass and myoglobin. Samples were obtained at 0, 4, 8, and 16 h postpresentation from 100 patients (41% with AMI). The order of sensitivity for the sample proportions taken at 0-2 h from the onset of symptoms was myoglobin > CK-MB2 > CK-MB. At all other time points, the sensitivity of CK-MB2 either equaled or surpassed that of both CK-MB and myoglobin, although the 95% confidence intervals for the population proportions each of these markers overlapped. Of the 41 AMI patients, 31 (76%) exhibited concurrent abnormal increases of CK-MB and %CK-MB2; the other 10 (24%; 8 non-Q wave, 2 Q wave) exhibited abnormal values for %CK-MB2 before their CK-MB exceeded the upper limit of normal. The specificity of myoglobin was statistically lower than that for either CK-MB2 or CK-MB at all time points.

Adult↗
PubMed1996

Protein tyrosine phosphatase regulation of endothelial cell apoptosis and differentiation.

Apoptosis, or programmed cell death, occurs during development and may also be an important factor in many diseases. However, little is known about the signal transduction pathways regulating apoptosis. In these studies, loss of endothelial cell-substrate attachment and apoptosis after removal of growth factors was associated with dephosphorylation of tyrosine residues at the cell periphery. Dephosphorylation of total cellular proteins accompanied apoptosis and was reduced by orthovanadate, an inhibitor of protein tyrosine phosphatases. Orthovanadate blocked the fragmentation of nuclear DNA, inhibited DNA laddering, and suppressed the expression of TRPM-2, an apoptosis-associated gene. The tyrosine phosphorylation levels of FAK125, erk1 (mitogen-activated kinase kinase), and cdc-2 were reduced during apoptosis. FAK125 dephosphorylation was inhibited by orthovanadate, but premature activation (tyrosine dephosphorylation) of cdc-2 was not. Orthovanadate was as effective as basic fibroblast growth factor in activating erk1 without increasing cell proliferation and in preventing the apoptosis of endothelial cells after treatment with tumor necrosis factor alpha. Endothelial cell differentiation on extracellular matrix (Matrigel) was also stimulated by orthovanadate in the absence of basic fibroblast growth factor without affecting growth arrest and inhibition of DNA synthesis. Expression of the cyclin-dependent kinase inhibitor p21 (Waf1/Cip1/Sdi1) was down-regulated during the early stages of differentiation, remained low for at least 6 hours as differentiation proceeded, and increased upon completion of differentiation. Cells that failed to down-regulate p21 mRNA on Matrigel in the absence of angiogenic factors underwent apoptosis. These results suggest that protein tyrosine phosphatases are actively involved in signal transduction during apoptosis and may regulate p21 expression to inhibit endothelial cell differentiation.

Apoptosis↗
PubMed1995

Adenovirus-mediated gene transfer of wild-type p53 results in melanoma cell apoptosis in vitro and in vivo.

Gene transfer techniques may provide efficient treatment for a variety of malignant neoplasms. A replication-deficient adenovirus (Ad) vector which carries the cDNA for wild-type p53 (AdCMV.p53) was tested for its in vitro and in vivo effects on the growth of murine melanoma cell line B16-G3.26 and human melanoma cell line SK-MEL-24. The growth of B16-G3.26 cells infected with AdCMV.p53 was inhibited when compared to the uninfected cells or cells infected with the control vector AdCMV.NLS beta gal. Similarly, the growth of SK-MEL-24 cells infected with AdCMV.p53 was also below that of AdCMV.NLS beta gal-infected and uninfected controls. DNA laddering using agarose gel electrophoresis and in situ labeling of DNA fragmentation (TUNEL) showed that AdCMV.p53-infected murine and human melanoma cells underwent apoptosis. Nude mice injected s.c. either with B16-G3.26 cells or with SK-MEL-24 cells developed localized tumors. These tumors were subsequently infiltrated with either AdCMV.p53, AdCMV.NLS beta gal or saline alone. One week after infection, B16-G3.26 tumors exposed to AdCMV.p53 were 2.5 times smaller than control tumors and exhibited DNA fragmentation. A similar growth-inhibitory effect of AdCMV.p53 was observed with SK-MEL-24 tumors. Thus, Ad-mediated wild-type p53 overexpression resulted in melanoma cell apoptosis and inhibition of melanoma growth in vitro and in vivo. These gene therapy approaches may be useful in targeting rapidly growing, malignant melanomas in a clinical setting.

Adenoviridae↗
PubMed1995

Transactivation ability of p53 transcriptional activation domain is directly related to the binding affinity to TATA-binding protein.

Tumor suppressor protein p53 is a potent transcriptional activator and regulates cell growth negatively. To characterize the transcriptional activation domain (TAD) of p53, various point mutants were constructed in the context of Gal4 DNA binding domain and tested for their transactivation ability. Our results demonstrated that the positionally conserved hydrophobic residues shared with herpes simplex virus VP16 and other transactivators are essential for transactivation. Also, the negatively charged residues and proline residues are necessary for full activity, but not essential for the activity of p53 TAD. Deletion analyses showed that p53 TAD can be divided into two subdomains, amino acids 1-40 and 43-73. An in vitro glutathione S-transferase pull-down assay establishes a linear correlation between p53 TAD-mediated transactivation in vivo and the binding activity of p53 TAD to TATA-binding protein (TBP) in vitro. Mutations that diminish the transactivation ability of Gal4-p53 TAD also impair the binding activity to TBP severely. Our results suggest that at least TBP is a direct target for p53 TAD and that the binding strength of TAD to TBP (TFIID) is an important parameter controlling activity of p53 TAD. In addition, circular dichroism spectroscopy has shown that p53 TAD peptide lacks any regular secondary structure in solution and that there is no significant difference between the spectra of the wild type TAD and that of the transactivation deficient mutant type.

Amino Acid Sequence↗
PubMed1995

Quantification of a dual angiotensin I-converting enzyme-neutral endopeptidase inhibitor and the active thiol metabolite in dog plasma by high-performance liquid chromatography with ultraviolet absorbance detection.

MDL 100,240 ([4S-[4 alpha,7 alpha(R*), 12b beta]]-7-[[2- (acetylthio)-1-oxo-3-phenylpropyl]amino]-1,2,3,4,6,7,8,12b-octahyd ro-6-oxo- pyrido[2,1-a][2]benzazepine-4-carboxylic acid, I) is the thioacetyl prodrug of the active thiol, MDL 100,173 (II), a dual inhibitor of angiotensin-I converting enzyme (ACE) and neutral endopeptidase (NEP). A drug which simultaneously inhibits both ACE and NEP may provide a unique therapy for hypertension and congestive heart failure. Methods based on high-performance liquid chromatography with UV absorbance detection at 200 nm were developed to support preclinical pharmacokinetic investigations. One method is used to measure unchanged I and free II, while the second method is used to quantify the total level of the thiol II after the plasma is incubated with the disulfide reducing agent, dithiothreitol. By either method, the analytes are quantified over the range of 25-1000 ng/ml with good accuracy and precision. The overall extraction efficiencies of unchanged I and free II in dog plasma were 79% and 86%, respectively, while the extraction efficiency of total II averaged 75%. Described in this report are the results obtained in validating the assay methods for measuring the compounds in plasma. Pharmacokinetic data are presented which were obtained by applying these methods to plasma collected from dogs dosed with I.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

The alpha-glucosidase I inhibitor castanospermine alters endothelial cell glycosylation, prevents angiogenesis, and inhibits tumor growth.

The development of drugs that target the tumor neovasculature may hold promise in inhibiting tumor growth. Experiments in vivo with castanospermine, an inhibitor of the glucosidases that convert protein N-linked high mannose carbohydrates to complex oligosaccharides, resulted in significant inhibition of tumor growth in nude mice. Angiogenesis to basic fibroblast growth factor in castanospermine-treated C57/BL mice was similarly reduced. Endothelial cell proliferation, invasion of basement membrane, and differentiation are crucial steps during neovascularization. In vitro differentiation models using Matrigel and postconfluent cultures of endothelial cells were used to study the effects of glycosidase inhibitors on endothelial cell behavior. FACS analysis of cell surface oligosaccharides using either Concanavalin A or L-phytohemagglutinin lectins confirmed an increase in high mannose groups and a decrease in tri- and tetra antennary beta-linked galactose-N-acetylglucosamine on mannose residues of Asn-linked oligosaccharides upon drug treatment. Castanospermine and the glucosidase inhibitor N-methyldeoxynojirimycin prevented the morphological differentiation of endothelial cells in vitro. These compounds did not alter the proliferation of cultured endothelial cells or their ability to attach to various extracellular matrix molecules. However, the cells showed a reduced ability to migrate and to invade basement membrane gels in vitro and an increased tendency to form aggregates that was inhibitable by D-mannose. These studies suggest that certain cell surface oligosaccharides are required for angiogenesis and that glucosidase inhibitors that alter these structures on endothelial cells are able to inhibit tumor growth.

1-Deoxynojirimycin↗
PubMed1995

Mechanisms of beta 1 integrin-dependent adherence of granulocytic HL60 to fibronectin.

We investigated the mechanism of beta 1 integrin-mediated adherence of stimulated granulocytic HL60 cells to fibronectin using a monoclonal antibody (15/7) that recognizes beta 1 integrins only when the receptors are active for ligand binding. Phorbol myristate acetate (PMA) stimulated expression of the 15/7 epitope on granulocytic HL60 by nearly fivefold but had an insignificant effect on the expression of the epitope on undifferentiated HL60 cells. These results paralleled the effect of PMA on HL60 and granulocytic HL60 adhesion to fibronectin, indicating that activation of beta 1 integrins is important for beta 1-mediated adherence of granulocytic HL60 cells to fibronectin. Agonists that stimulate alpha 5 beta 1-dependent human polymorphonuclear leukocyte (PMN) adhesion to fibronectin (C5a and PMA) also upregulated the 15/7 epitope on purified human PMNs. Although PMA rapidly induces increased levels of filamentous actin (F-actin) in granulocytic HL60 cells and a decrease in F-actin levels in undifferentiated HL60 cells, depolymerization of the actin cytoskeleton with cytochalasin B did not affect increased expression of the 15/7 epitope on granulocytic HL60 cells. Cytochalasin B did, however, inhibit granulocytic HL60 adherence to fibronectin by 50%, demonstrating that actin polymerization is important for optimal beta 1-dependent granulocytic adherence.

Actins↗
PubMed1995

Intensification and depletion of specific bulky renal DNA adducts (I-compounds) following exposure of male F344 rats to the renal carcinogen ferric nitrilotriacetate (Fe-NTA).

The effects of the renal carcinogen ferric nitrilotriacetate (Fe-NTA) on kidney DNA of male F344 rats were studied to determine whether bulky DNA oxidation products (putative intrastrand crosslinks) could be detected by 32P-postlabeling in the target organ of carcinogenesis. Rats (10-11 weeks old) were given a single dose of Fe-NTA (15 mg Fe/kg body weight) i.p. at 3:00 pm. After 5 h, renal DNA from Fe-NTA-treated and vehicle control animals was assayed by 32P-postlabeling. Thin-layer chromatography and quantitative analysis of two labeled nucleotide fractions of increasing polarity, L and C, showed that three spots (L1, L2, and C3) were intensified 3.5- to 4.2-fold in treated animals. L1 consisted of subfractions L1a, L1b, and L1c, which could be resolved chromatographically. L1c, L2, and C3 were identical to DNA oxidation products generated by the Fenton reaction in vitro, while L1a and L1b apparently did not arise by this mechanism. DNA damage and toxicity appeared reduced in younger animals and animals treated in the morning, presumably due to differences in antioxidant defenses. Liver and lung (non-target organs) DNA did not exhibit enhanced L1, L2, and C3 spots. In addition to augmenting renal I-compounds, Fe-NTA reduced the levels of three major polar kidney I-compounds (C4, C5, and C6) to 22-53% of control. This reduction did not appear to arise by direct oxidative DNA damage, resembling the previously documented loss of liver I-compounds induced by numerous hepatocarcinogens. Two of these I-compounds (C4 and C5) have been reported to exhibit positive linear correlations with median lifespan of male F344 rats. The pleiotropic response of kidney I-compound levels to Fe-NTA was consistent with different roles of different types (I and II) of I-compounds in Fe-NTA-mediated renal carcinogenesis. The results strongly support a causal relationship between oxidative DNA lesions and Fe-NTA-mediated carcinogenesis.

Age Factors↗
PubMed1995

Differential expression of protein kinase C isoforms in glial and neuronal cells. Translocation and down-regulation of PKC isoforms in C6 glioma and NG 108-15 hybrid cells: effects of extracellular Ca(2+)-depletion.

Protein kinase C (PKC), the major receptor for tumor-promoting phorbol esters, consists of a family of at least 12 distinct lipid-regulated enzymes. We examined the expression and regulation of PKC isoforms in C6-glioma and NG 108-15 hybrid cells. Western blot analysis indicated that both cell lines express four PKC isoforms, PKC alpha, PKC delta, PKC epsilon and PKC zeta. The expression of PKC alpha and PKC delta in C6-glioma cells was more abundant than NG 108-15 cells, however, PKC epsilon in NG 108-15 was more abundant than C6-glioma cells in which PKC epsilon was almost undetectable. Treatment of both cells with TPA for 10 min resulted in the translocation of PKC alpha, PKC delta and PKC epsilon to the membrane fraction. When the intact cells were treated with Ca(2+)-free, EGTA containing physiological saline solution, the membrane bound conventional PKC alpha (cPKC alpha) was greatly reduced and cytosolic cPKC alpha was only slightly increased. However, neither membrane bound nor cytosolic new PKC delta (nPKC delta), nPKC epsilon and atypical PKC zeta (aPKC zeta) was affected by extracellular Ca2+ depletion. In this condition, the translocation of cPKC alpha, nPKC delta and nPKC epsilon induced by TPA still occurred, however, that of cPKC alpha was reduced more than in the normal condition. After long-term treatment (17 h) with TPA, cPKC alpha, nPKC delta and nPKC epsilon were down-regulated both in the cytosol and membrane. The phenomena of cPKC alpha were confirmed by measuring the PKC activity with histone as the substrate. From in vitro endogenous phosphorylation studies, a 31 kDa substrate protein phosphorylation in C6 glioma cell membrane and 31 and 26 kDa proteins in NG 108-15 cell membrane were increased in the translocation but disappeared in the down-regulation of PKC.

Animals↗
PubMed1995

Attachment of intrinsically and extrinsically aged fibroblasts on collagen and fibronectin.

In the present study we compare human dermal fibroblasts from donors of different age and from sites differing in sun exposure for their capacity to adhere to collagen or fibronectin. Attachment of cells was not dependent on the collagen concentration but was clearly dependent on the fibronectin concentration used for the coating of the plastic surfaces. Attachment of fibroblasts to collagen and fibronectin is dominated by specific integrin binding: only few cells were able to attach to collagen after inhibition with an anti-VLA 2 antibody, or to attach to fibronectin after inhibition with an anti-VLA 5 antibody. On unexposed sites, cells from old donors showed a significantly increased adhesion capacity on collagen (plus 50.7%) and on fibronectin (plus 62.4%) and an increased staining pattern of VLA 2 and VLA 5 integrins in immunohistochemistry in comparison with young donors. In contrast fibroblasts of chronically sun-exposed skin had a significantly decreased adhesion capacity both on collagen (minus 55.3%) and on fibronectin (minus 46.5%) and a poor staining pattern of the above integrins in comparison with cells from solely aged skin (unexposed sites of old donors). Adhesion of all cells could be inhibited by specific integrin antibodies showing that the employed antibodies were able to detect the epitopes responsible for attachment. Intrinsic and extrinsic aging are able to alter cellular properties of mesenchymal cells, such as adhesion to physiologically relevant macromolecules of the extracellular matrix.

Adult↗
PubMed1995

Platinum-Taxol non-cross resistance in epithelial ovarian cancer.

The aim of this study was to assess the clinical evidence for platinum-Taxol non-cross-resistance in patients with epithelial ovarian cancer. Unlike other studies, only patients who had demonstrably progressive disease on platinum therapy were analysed. Patients received 135-200 mg m-2 of Taxol over 3 or 24 h and all patients were assessed for response by computerised axial tomography. The overall response rate was 22.2% (8/36 patients, 95% CI 10-39%). Only patients who received > or = 175 mg m-2 of Taxol responded (26.7%; 8/30 patients, 95% CI 12-46%). No complete responses were seen and the duration of response was short, median 7 months (range 5-9+). Response was associated with a short treatment-free interval (P = 0.02); only those who were treated immediately after they had progressed on their previous platinum therapy responded. Response duration was associated with a good performance status (P < 0.05). Platinum and Taxol are non-cross-resistant in a proportion of patients and therefore patients who are resistant to platinum compounds may benefit from Taxol although the duration of any response is short. These data support current strategies that involve combining Taxol with platinum compounds as first-line therapy in advanced epithelial ovarian cancer.

Adult↗