RESUMEN
There are an estimated 1 billion cases of superficial fungal infection globally. Fungal pathogens form biofilms within wounds and delay the wound healing process. Miconazole and terbinafine are commonly used to treat fungal infections. They induce the accumulation of reactive oxygen species (ROS) in fungi, resulting in the death of fungal cells. ROS are highly reactive molecules, such as oxygen (O2), superoxide anion (O2â¢-), hydrogen peroxide (H2O2) and hydroxyl radicals (â¢OH). Although ROS generation is useful for killing pathogenic fungi, it is cytotoxic to human keratinocytes. To the best of our knowledge, the effect of miconazole and terbinafine on HaCaT cells has not been studied with respect to intracellular ROS stimulation. We hypothesized that miconazole and terbinafine have anti-wound healing effects on skin cells when used in antifungal treatment because they generate ROS in fungal cells. We used sulforhodamine B protein staining to investigate cytotoxicity and 2',7'-dichlorofluorescein diacetate to determine ROS accumulation at the 50% inhibitory concentrations of miconazole and terbinafine in HaCaT cells. Our preliminary results showed that topical treatment with miconazole and terbinafine induced cytotoxic responses, with miconazole showing higher cytotoxicity than terbinafine. Both the treatments stimulated ROS in keratinocytes, which may induce oxidative stress and cell death. This suggests a negative correlation between intracellular ROS accumulation in keratinocytes treated with miconazole or terbinafine and the healing of fungi-infected skin wounds.
Asunto(s)
Peróxido de Hidrógeno , Miconazol , Humanos , Peróxido de Hidrógeno/farmacología , Queratinocitos , Miconazol/metabolismo , Miconazol/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Terbinafina/metabolismo , Terbinafina/toxicidadRESUMEN
Antimicrobial resistance remains a serious problem that results in high mortality and increased healthcare costs globally. One of the major issues is that resistant pathogens decrease the efficacy of conventional antimicrobials. Accordingly, development of novel antimicrobial agents and therapeutic strategies is urgently needed to overcome the challenge of antimicrobial resistance. A potential strategy is to kill pathogenic microorganisms via the formation of reactive oxygen species (ROS). ROS are defined as a number of highly reactive molecules that comprise molecular oxygen (O2), superoxide anion (O2â¢-), hydrogen peroxide (H2O2) and hydroxyl radicals (â¢OH). ROS exhibit antimicrobial actions against a broad range of pathogens through the induction of oxidative stress, which is an imbalance between ROS and the ability of the antioxidant defence system to detoxify ROS. ROS-dependent oxidative stress can damage cellular macromolecules, including DNA, lipids and proteins. This article reviews the antimicrobial action of ROS, challenges to ROS hypothesis, work to solidify ROS-mediated antimicrobial lethality hypothesis, recent developments in antimicrobial agents using ROS as an antimicrobial strategy, safety concerns related to ROS, and future directions in ROS research.
Asunto(s)
Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , ADN Bacteriano/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Animales , Humanos , Estrés OxidativoRESUMEN
Optimal haemophilia care is best established and implemented through a well-coordinated plan guided by clearly defined principles and priorities. A document which enunciates those details is therefore important. A successful example of this approach is the definition of principles of haemophilia care (PHC) outlined by the European Association for Haemophilia and Associated Disorders (EAHAD) and also the World Federation of Hemophilia. A similar document applicable to the Asia-Pacific region must take into account not only the highly varied healthcare systems but also the tremendous socio-economic and cultural diversities which impact provision of such care. The Asia-Pacific Haemophilia Working Group (APHWG), representing the countries in this region, has prepared this perspective of the PHC. While endorsing the overall framework outlined by EAHAD, this APHWG document emphasizes regional priorities on education and training of healthcare personnel in the diagnosis and management of hereditary bleeding disorders. Central coordinating agencies with wide stakeholder input, networks of haemophilia treatment centres and national registries as well as robust processes for procurement and distribution of safe and effective clotting factor concentrates (CFCs), implementation of prophylaxis programmes and management of patients with inhibitors should also be developed. The implementation of these strategies should lead to establishment of good comprehensive care programmes. This document should also be an advocacy tool to lobby for improved care for people with haemophilia (PWH) in the region. We urge national healthcare policy makers to consider these principles and initiate strong and decisive action to reach these goals.
Asunto(s)
Hemofilia A , Atención al Paciente/métodos , Asia , Factores de Coagulación Sanguínea/uso terapéutico , Comorbilidad , Hemofilia A/tratamiento farmacológico , Hemofilia A/epidemiología , Hemofilia A/inmunología , HumanosRESUMEN
Antimicrobial resistance of disease-related microorganisms is considered a worldwide prevalent and serious issue which increases the failure of treatment outcomes and leads to high mortality. Considering that the increased resistance to systemic antimicrobial therapy often needs of the use of more toxic agents, topical antimicrobial therapy emerges as an attractive route for the treatment of infectious diseases. The topical antimicrobial therapy is based on the absorption of high drug doses in a readily accessible skin surface, resulting in a reduction of microbial proliferation at infected skin sites. Topical antimicrobials retain the following features: (a) they are able to escape the enzymatic degradation and rapid clearance in the gastrointestinal tract or the first-pass metabolism during oral administration; (b) alleviate the physical discomfort related to intravenous injection; (c) reduce possible adverse effects and drug interactions of systemic administrations; (d) increase patient compliance and convenience; and (e) reduce the treatment costs. Novel antimicrobials for topical application have been widely exploited to control the emergence of drug-resistant microorganisms. This review provides a description of antimicrobial resistance, common microorganisms causing skin and soft tissue infections, topical delivery route of antimicrobials, safety concerns of topical antimicrobials, recent advances, challenges and future prospective in topical antimicrobial development.
Asunto(s)
Antibacterianos/administración & dosificación , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Administración Tópica , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/metabolismo , Farmacorresistencia Bacteriana , Humanos , Enfermedades Cutáneas Bacterianas/microbiología , Infecciones de los Tejidos Blandos/microbiologíaRESUMEN
Two complexes dichloro(9,9-dihexyl-4,5-diazafluorene)platinum(II) (Pt-DHF) and dichloro(9,9-dihexyl-4,5-diazafluorene)palladium(II) (Pd-DHF) were synthesized and their in vivo antitumour activity was investigated using an athymic nude mice model xenografted with human Hep3B carcinoma cells. Pt-DHF- and Pd-DHF-treated groups showed significant tumour growth inhibition (with about 9-fold and 3-fold tumour growth retardation) when compared with the vehicle control group. The liver toxicology effects on the animals of the two compounds were investigated. Pt-DHF and Pd-DHF-treated groups had a lower alanine transaminase and aspartate transaminase values than those of the vehicle treated group as the animals from the vehicle control group had very heavy hepatoma burden. We assume that both complexes could be further investigated as effective antitumour agents and it is worthwhile to study their underlying working mechanism.
Asunto(s)
Complejos de Coordinación/síntesis química , Compuestos Organoplatinos/síntesis química , Compuestos Organoplatinos/farmacología , Paladio/química , Platino (Metal)/química , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Modelos Animales de Enfermedad , Activación Enzimática/efectos de los fármacos , Xenoinjertos , Humanos , Hígado/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Ratones , Compuestos Organoplatinos/química , Compuestos Organoplatinos/uso terapéutico , Paladio/farmacología , Paladio/uso terapéutico , Platino (Metal)/farmacología , Platino (Metal)/uso terapéuticoRESUMEN
Tumour growth is closely related to the development of new blood vessels to supply oxygen and nutrients to cancer cells. Without the neovascular formation, tumour volumes cannot increase and undergo metastasis. Antiangiogenesis is one of the most promising approaches for antitumour therapy. The exploration of new antiangiogenic agents would be helpful in antitumour therapy. Quinoline is an aromatic nitrogen compound characterized by a double-ring structure which exhibits a benzene ring fused to pyridine at two adjacent carbon atoms. The high stability of quinoline makes it preferable in a variety of therapeutic and pharmaceutical applications, including antitumour treatment. This work is to examine the potential antiangiogenic activity of the synthetic compound 2-Formyl-8-hydroxy-quinolinium chloride. We found that 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of human umbilical vein endothelial cells in vitro. Using the diethylnitrosamine-induced hepatocarcinogenesis model, 2-Formyl-8-hydroxy-quinolinium chloride showed strong antiangiogenic activity. Furthermore, 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of large Hep3B xenografted tumour from the nude mice. We assume that 2-Formyl-8-hydroxy-quinolinium chloride could be a potential antiangiogenic and antitumour agent and it is worthwhile to further study its underlying working mechanism.
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Hidroxiquinolinas/farmacología , Compuestos de Quinolinio/farmacología , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Carcinogénesis/patología , Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Dietilnitrosamina , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Hidroxiquinolinas/química , Hidroxiquinolinas/uso terapéutico , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Ratones Endogámicos C57BL , Ratones Desnudos , Compuestos de Quinolinio/química , Compuestos de Quinolinio/uso terapéutico , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
A series of ruthenium(II) bis(2,2'-bipyridyl) complexes containing N-phenyl-substituted diazafluorenes (Ru-C1, Ru-C6, Ru-C7 and Ru-F) was synthesized and their potential antibacterial activity against methicillin resistant Staphylococcus aureus (MRSA) was investigated. The Ru-C7 complex showed significant improvement in both minimum inhibitory concentration (MIC, 6.25 µg mL(-1)) and minimum bactericidal concentration (MBC, 25 µg mL(-1)) towards MRSA when compared with those of methicillin (positive control) (MIC = 25 µg mL(-1) and MBC = 100 µg mL(-1)). The Ru-C7 complex possessed much stronger antibacterial effects than the Ru-C6 complex (MIC, 25 µg mL(-1), MBC, >100 µg mL(-1)). Both Ru-C6 and Ru-C7 complexes were also demonstrated to be biologically safe when tested on normal human skin keratinocytes.
Asunto(s)
Antibacterianos/farmacología , Complejos de Coordinación/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Rutenio/farmacología , Administración Tópica , Antibacterianos/administración & dosificación , Antibacterianos/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/administración & dosificación , Complejos de Coordinación/química , Fluorenos/química , Humanos , Queratinocitos/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Rutenio/administración & dosificación , Rutenio/químicaRESUMEN
The therapeutic efficiency and topical performance of drug-containing microcapsules varied when the drugs existed in an internal oil phase or an internal aqueous phase within the wall shell or wall matrix of microcapsules. In this study, chitosan-based (oil-in-water) and agar-gelatin-based (water-in-oil) microencapsulation systems containing berberine were applied to cotton fabrics to provide an anti-Staphylococcus aureus activity for textile materials. The berberine microcapsule-treated cotton samples were subjected to various washing cycles and their surface morphology, chemical compositions and antibacterial property were investigated after washing. The SEM images and Fourier transform infrared analysis showed that the amount of microcapsules on cotton samples decreased gradually with an increase in washing cycles. After 20 washing cycles, the cotton fabrics with agar-gelatin (water-in-oil) microcapsules containing berberine still exhibited the anti-S. aureus activity. However, the chitosan-based (oil-in-water) system did not show any growth inhibition towards S. aureus but only in the contact areas.
Asunto(s)
Antibacterianos/química , Berberina/química , Fibra de Algodón , Staphylococcus aureus/crecimiento & desarrollo , Textiles , CápsulasRESUMEN
A novel compound, (5-(dimethylamino)-N-(4-ethynylphenyl)-1-naphthalenesulfonamide), was prepared and characterized; it shows dual functional roles as an effective antitumor and a two-photon induced bio-imaging agent.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Colorantes Fluorescentes/química , Colorantes Fluorescentes/farmacología , Naftalenos/farmacología , Fotones , Sulfonamidas/farmacología , Animales , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Colorantes Fluorescentes/síntesis química , Humanos , Ratones , Ratones Desnudos , Estructura Molecular , Naftalenos/síntesis química , Naftalenos/química , Estereoisomerismo , Relación Estructura-Actividad , Sulfonamidas/síntesis química , Sulfonamidas/químicaRESUMEN
The US Food and Drug Administration has updated the label information for warfarin to encourage the use of genetic information before initiating treatment with the drug. We used decision-tree modeling to simulate the outcomes of CYP2C9 and vitamin K epoxide reductase complex 1 (VKORC1) genotype-guided dosing in patients in whom warfarin therapy is to be initiated. The inputs for the model were derived from the literature. The incremental costs per unit outcome improved (ICERs) were US$347,059 per quality-adjusted life-year (QALY) gained, $170,192 per adverse event averted, and $1,106,250 per life saved. The outcomes of 10,000 Monte Carlo simulations demonstrate that the ICER per QALY gained was >$50,000 62.1% of the time. ICER was sensitive to baseline international normalized ratio (INR) control, reduction in out-of-range INRs by genotype-guided dosing, and genotyping cost. In conclusion, genotype-guided dosing for warfarin therapy does not appear to be cost-effective, with the potential ICER per QALY being >$50,000. Lowering the genotyping cost, improving effectiveness of INR control of the genotype-guided dosing algorithm, and applying the algorithm in practice sites with high out-of-range INRs would improve the cost-effectiveness of the dosing algorithm.
Asunto(s)
Anticoagulantes/administración & dosificación , Hidrocarburo de Aril Hidroxilasas/genética , Árboles de Decisión , Oxigenasas de Función Mixta/genética , Warfarina/administración & dosificación , Algoritmos , Anticoagulantes/efectos adversos , Anticoagulantes/economía , Análisis Costo-Beneficio , Citocromo P-450 CYP2C9 , Etiquetado de Medicamentos , Genotipo , Humanos , Relación Normalizada Internacional , Método de Montecarlo , Años de Vida Ajustados por Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Estados Unidos , United States Food and Drug Administration , Vitamina K Epóxido Reductasas , Warfarina/efectos adversos , Warfarina/economíaRESUMEN
OBJECTIVE: The aims of this study were to evaluate the use of antimicrobial agents in the fever wards of a Hong Kong teaching hospital and to identify those factors associated with treatment failure and having an influence on the total direct medical costs of antimicrobial therapy. METHODS: This was a retrospective observational study. Demographic and clinical data were collected on 123 patients admitted to the fever wards in a local teaching hospital between July 2004 and August 2004. Multivariate analyses were performed to identify factors associated with treatment failure and the total direct medical treatment cost. RESULTS: The rate of treatment failure was 30.1% (37 out of 123 patients). The mean total direct medical cost was HK$ 26,442 +/- 17,153 (US$ 1 = HK$ 7.8). The empirical therapy in 90 (73.2%) patients complied with the institutional guidelines. 25 (20.3%) patients were eligible for renal dosage adjustment and in 7 (28%) of these patients the dosage of antimicrobial agents was renally adjusted. Of the 27 patients in whom pathogens were identified, 9 (33.3%) patients were eligible for antimicrobial streamlining (changing to an antibiotic with a narrower spectrum) but streamlining was only done in 2 (22.2%) patients. Multivariate analysis showed that the history of malignant diseases (RR = 5.07; 95% CI = 1.06 - 24.22) and non-compliance with the institutional treatment guidelines for selection of empirical antimicrobial therapy (RR = 3.58; 95% CI = 1.35 - 9.54) were risk factors associated with treatment failure. Duration of intravenous antimicrobial therapy was associated with the total cost of treatment (RR = 1.60; 95% CI = 1.35 - 2.10). CONCLUSION: Non-compliance with treatment guidelines in empirical antimicrobial treatment and the duration of intravenous antimicrobial therapy were modifiable risk factors for treatment failure and total treatment cost, respectively.
Asunto(s)
Antiinfecciosos/economía , Antiinfecciosos/uso terapéutico , Enfermedades Transmisibles/tratamiento farmacológico , Enfermedades Transmisibles/economía , Hospitales de Enseñanza/economía , Anciano , Anciano de 80 o más Años , Femenino , Fiebre , Adhesión a Directriz , Costos de la Atención en Salud , Hong Kong , Humanos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Insuficiencia del TratamientoRESUMEN
BACKGROUND AND AIMS: Severe acute respiratory syndrome (SARS) is a virulent viral infection that affects a number of organs and systems. This study examined if SARS may result in cardiovascular complications. METHODS AND RESULTS: 121 patients (37.5 (SD13.2) years, 36% male) diagnosed to have SARS were assessed continuously for blood pressure, pulse, and temperature during their stay in hospital. Hypotension occurred in 61 (50.4%) patients in hospital, and was found in 28.1%, 21.5%, and 14.8% of patients during the first, second, and third week, respectively. Only one patient who had transient echocardiographic evidence of impaired left ventricular systolic function required temporary inotropic support. Tachycardia was present in 87 (71.9%) patients, and was found in 62.8%, 45.4%, and 35.5% of patients from the first to third week. It occurred independent of hypotension, and could not be explained by the presence of fever. Tachycardia was also present in 38.8% of patients at follow up. Bradycardia only occurred in 18 (14.9%) patients as a transient event. Reversible cardiomegaly was reported in 13 (10.7%) patients, but without clinical evidence of heart failure. Transient atrial fibrillation was present in one patient. Corticosteroid therapy was weakly associated with tachycardia during the second (chi(2) = 3.99, p = 0.046) and third week (chi(2) = 6.53, p = 0.01), although it could not explain tachycardia during follow up. CONCLUSIONS: In patients with SARS, cardiovascular complications including hypotension and tachycardia were common but usually self limiting. Bradycardia and cardiomegaly were less common, while cardiac arrhythmia was rare. However, only tachycardia persisted even when corticosteroid therapy was withdrawn.
Asunto(s)
Enfermedades Cardiovasculares/virología , Síndrome Respiratorio Agudo Grave/complicaciones , Presión Sanguínea , Enfermedades Cardiovasculares/fisiopatología , Femenino , Hospitalización , Humanos , Masculino , Factores de Riesgo , Síndrome Respiratorio Agudo Grave/fisiopatologíaRESUMEN
AIM: To examine the optimal range of International Normalized Ratio (INR) for Chinese patients receiving warfarin for moderate-intensity anticoagulation. METHODS: This was a retrospective cohort study conducted at the ambulatory setting of a 1400-bed public teaching hospital in Hong Kong. The INR measurements and occurrence of serious or life-threatening haemorrhagic and thromboembolic events among patients newly started on warfarin from 1 January 1999 to 30 June 2001 for indications with target INR 2-3 were analysed. The INR-specific incidence of bleeding and thromboembolism were calculated. RESULTS: A total of 491 patients were included, contributing to 453 patient-years of observation period. Forty-seven of the 491 patients experienced 25 haemorrhagic events (5.5 per 100 patient-years) and 27 thromboembolic events (6.0 per 100 patient-years). The percentage of patient-time spent within therapeutic INR range (2-3), INR <2 and INR >3 were 50, 44 and 6%, respectively. The incidence of either haemorrhagic or thromboembolic events was lowest (< or =4 events per 100 patient-years) at INR values between 1.8 and 2.4. CONCLUSIONS: An INR of 1.8-2.4 appeared to be associated with the lowest incidence rate of major bleeding or thromboembolic events in a cohort of Hong Kong Chinese patients receiving warfarin therapy for moderate-intensity anticoagulation.
Asunto(s)
Anticoagulantes/uso terapéutico , Hemorragia/sangre , Relación Normalizada Internacional , Tromboembolia/sangre , Warfarina/uso terapéutico , Distribución por Edad , Anciano , Pueblo Asiatico , Estudios de Cohortes , Hemorragia/etiología , Hong Kong , Humanos , Estudios Retrospectivos , Tromboembolia/etiologíaRESUMEN
Severe acute respiratory syndrome is a new disease that is highly contagious and is spreading in the local community and worldwide. This report is of a hospital medical officer with severe acute respiratory syndrome. He presented with sudden onset of fever, chills, myalgia, headache, and dizziness in early March 2003. He developed progressive respiratory symptoms and bilateral pulmonary infiltrates during the second week of his illness. Blood tests showed lymphopenia, mild thrombocytopenia, and prolonged activated partial thromboplastin time with normal d-dimer level. His chest condition gradually responded to ribavirin and corticosteroids, and serial chest X-ray showed resolving pulmonary infiltrates. The importance of early diagnosis lies in the potential for early treatment, leading to better response.
Asunto(s)
Síndrome Respiratorio Agudo Grave/terapia , Adulto , Humanos , Masculino , MédicosAsunto(s)
Enfermedades Autoinmunes/inmunología , Enfermedades del Sistema Endocrino/inmunología , Neuritis Óptica/complicaciones , Neuritis Óptica/inmunología , Adulto , Enfermedades Autoinmunes/patología , Enfermedades Autoinmunes/fisiopatología , Enfermedad de Castleman/inmunología , Enfermedad de Castleman/fisiopatología , Vértebras Cervicales , Enfermedad Crónica , Enfermedades del Sistema Endocrino/patología , Enfermedades del Sistema Endocrino/fisiopatología , Resultado Fatal , Femenino , Humanos , Hiperprolactinemia/inmunología , Hiperprolactinemia/fisiopatología , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Ganglios Linfáticos/fisiopatología , Persona de Mediana Edad , Mielitis/inmunología , Mielitis/fisiopatología , Neuritis Óptica/tratamiento farmacológico , Insuficiencia Ovárica Primaria/inmunología , Insuficiencia Ovárica Primaria/fisiopatología , Embolia Pulmonar/inmunología , Embolia Pulmonar/fisiopatología , Púrpura Trombocitopénica Idiopática/inmunología , Púrpura Trombocitopénica Idiopática/fisiopatología , Púrpura Trombocitopénica Idiopática/cirugía , Cuadriplejía/inmunología , Cuadriplejía/fisiopatología , Recurrencia , Trombosis de la Vena/inmunología , Trombosis de la Vena/fisiopatologíaRESUMEN
BACKGROUND: The fruit extract of Gleditsia sinensis Lam. (GSE) is a traditional herbal medicine that is saponin-rich. However, its activity on solid tumour cell lines has never been demonstrated. METHODS: The activity of GSE was demonstrated in four cancer cell lines (breast cancer MCF-7, MDA-MB231, hepatoblastoma HepG2 and oesophageal squamous carcinoma cell line SLMT-1) using MTT assay, anchorage-independent clonogenicity assay, DNA laddering and in situ cell death detection. RESULTS: The mean MTT(50) (the mean concentration of GSE to reduce MTT activity by 50%) ranged from 16 to 20 microg/ml of GSE. An anchorage-independent clonogenicity assay showed that all of the four solid tumour cell lines gradually lost their regeneration potential after treatment with GSE, DNA fragmentation and TUNEL analysis demonstrated that the action of GSE is both dose- and time course-dependent. CONCLUSIONS: Our results suggest that GSE has a cytotoxic activity and can induce apoptosis in human solid tumour cell lines.