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Biomedical subjects

L Sutton

Publications and source records attributed to L Sutton.

At least 19 recordsLinked to original sources
PubMed2006

Does rural or urban residence make a difference to neonatal outcome in premature birth? A regional study in Australia.

BACKGROUND: Patients living in rural areas may be at a disadvantage in accessing tertiary health care. AIM: To test the hypothesis that very premature infants born to mothers residing in rural areas have poorer outcomes than those residing in urban areas in the state of New South Wales (NSW) and the Australian Capital Territory (ACT) despite a coordinated referral and transport system. METHODS: "Rural" or "urban" status was based on the location of maternal residence. Perinatal characteristics, major morbidity and case mix adjusted mortality were compared between 1879 rural and 6775 urban infants <32 weeks gestational age, born in 1992-2002 and admitted to all 10 neonatal intensive care units in NSW and ACT. RESULTS: Rural mothers were more likely to be teenaged, indigenous, and to have had a previous premature birth, prolonged ruptured membrane, and antenatal corticosteroid. Urban mothers were more likely to have had assisted conception and a caesarean section. More urban (93% v 83%) infants were born in a tertiary obstetric hospital. Infants of rural residence had a higher mortality (adjusted odds ratio (OR) 1.26, 95% confidence interval (CI) 1.07 to 1.48, p = 0.005). This trend was consistently seen in all subgroups and significantly for the tertiary hospital born population and the 30-31 weeks gestation subgroup. Regional birth data in this gestational age range also showed a higher stillbirth rate among rural infants (OR 1.20, 95% CI 1.09 to 1.32, p<0.001). CONCLUSIONS: Premature births from rural mothers have a higher risk of stillbirth and mortality in neonatal intensive care than urban infants.

Australian Capital Territory↗
PubMed2005

The effects of antipsychotics on beta-catenin, glycogen synthase kinase-3 and dishevelled in the ventral midbrain of rats.

Protein kinase B and glycogen synthase kinase-3 have been identified as susceptibility genes for schizophrenia and altered protein and mRNA levels have been detected in the brains of schizophrenics post-mortem. Recently, we reported that haloperidol, clozapine and risperidone alter glycogen synthase kinase-3 and beta-catenin protein expression and glycogen synthase kinase-3 phosphorylation levels in the rat prefrontal cortex and striatum. In the current study, beta-catenin, adenomatous polyposis coli, Wnt1, dishevelled and glycogen synthase kinase-3 were examined in the ventral midbrain and hippocampus using western blotting. In addition, beta-catenin and GSK-3 were examined in the substantia nigra and ventral tegmental area using confocal and fluorescence microscopy. The results indicate that repeated antipsychotic administration results in significant elevations in glycogen synthase kinase-3, beta-catenin and dishevelled-3 protein levels in the ventral midbrain and hippocampus. Raclopride causes similar changes in beta-catenin and GSK-3 in the ventral midbrain, suggesting that D2 dopamine receptor antagonism mediated the changes observed following antipsychotic administration. In contrast, amphetamine, a drug capable of inducing psychotic episodes, had the opposite effect on beta-catenin and GSK-3 in the ventral midbrain. Collectively, the results suggest that antipsychotics may exert their beneficial effects through modifications to proteins that are associated with the canonical Wnt pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Self-poisoning suicides in England: a multicentre study.

BACKGROUND: Suicide by self-poisoning is an important cause of death worldwide. A substantial proportion of those with a fatal outcome may come into contact with medical services before they die. AIM: To estimate the proportion of self-poisoning suicides who reached hospital alive; to compare those who reached hospital alive with those who did not; to describe in detail the clinical characteristics and medical management of those dying in hospital. DESIGN: Retrospective audit. METHODS: We studied 24 coroners' jurisdictions across England, reviewing coroners' files and identifying all suicides by self-poisoning (drugs and other ingestible poisons) from 1 January 2001 to 31 December 2001. RESULTS: Of the 214 individuals who completed suicide by self-poisoning during the study period, 49 (23%) reached hospital alive. Those reaching hospital were more likely to be female, more likely to have ingested paracetamol and less likely to have ingested co-proxamol. In the hospital sample, the commonest causes of death were respiratory (n = 10), hepatic or hepatorenal (n = 8), cardiac (n = 5), or a result of hypoxic brain injury (n = 5). Only 18% of in-hospital deaths occurred within 24 h of the overdose. DISCUSSION: Extrapolating to England as a whole, we might expect 300 self-poisoning suicides per year to reach hospital alive (6% of all suicides). Improved medical management might produce a small but significant reduction in the rate of suicide. Such interventions should not be restricted to the emergency care domain. Further research will help to clarify the likely contribution of improved medical management to suicide prevention.

Adult↗
PubMed2005

Co-proxamol and suicide: preventing the continuing toll of overdose deaths.

Restricting means for suicide is a key element in suicide prevention strategies of all countries where these have been introduced. Preventing deaths from analgesic overdoses is highlighted in the National Suicide Prevention Strategy for England. The problem of self-poisoning with the prescription-only drug co-proxamol (dextropropoxyphene plus paracetamol) has received attention in several countries. We have conducted a review of the international literature related to possible strategies to tackle this problem. In England and Wales in 1997-1999, 18% of drug-related suicides involved co-proxamol; these constituted 5% of all suicides. Death usually results from the toxic effects of dextropropoxyphene on respiration or cardiac function. Death from co-proxamol overdose may occur rapidly, the lethal dose can be relatively low, and the effects are potentiated by alcohol and other CNS depressants. The majority of co-proxamol overdose deaths occur before hospital treatment can be received. The risk can extend to others in the household of the person for whom the drug is prescribed. While there is limited evidence that educational strategies have been effective in reducing deaths from co-proxamol poisoning, initiatives in Scandinavia, Australia and the UK to restrict availability of co-proxamol have produced promising results. Given the paucity of evidence for superior therapeutic efficacy of co-proxamol over other less toxic analgesics, there are good reasons to question whether it should continue to be prescribed.

Acetaminophen↗
PubMed2005

A multicentre study of coproxamol poisoning suicides based on coroners' records in England.

AIMS: To examine in detail a series of coproxamol overdose deaths in order to provide information that will assist in the development of strategies to prevent such fatalities. METHOD: Inquest records in 24 coroners' jurisdictions in England on deaths between January 2000 and December 2001 which received a verdict of either suicide or undetermined cause (with a high or moderate probability of suicide) were examined. RESULTS: One hundred and twenty-three coproxamol poisoning suicides were identified. Alcohol was involved in 58.5% of the overdoses and these individuals generally had lower blood drug levels and consumed fewer tablets. Younger people were more likely to have consumed alcohol and to have lower levels of suicide intent. Nearly half the individuals had a history of self harm, and a third were under psychiatric care. The coproxamol had been prescribed for the individual in 81.5% of cases, although only in 55.0% of those aged 10-34 years. In other cases the source of the coproxamol was nearly always a family member or partner. Some deaths resulted from relatively small overdoses. CONCLUSIONS: Strategies to reduce self poisoning deaths due to coproxamol should take account of the high toxicity of coproxamol in overdose, especially when combined with alcohol, and the fact that risk of death extends beyond the person for whom the drug is prescribed.

Acetaminophen↗
PubMed2004

Donor lymphocyte infusion to treat relapse after allogeneic bone marrow transplantation for myelodysplastic syndrome.

Donor lymphocyte infusion has become established as a salvage therapy for patients with hematological disorders relapsing after allogeneic bone marrow transplantation (BMT). The role of donor lymphocyte infusion for patients with myelodysplastic syndrome (MDS) remains to be established. Between July 1993 and October 2001, 14 patients with MDS relapsing after allogeneic BMT received DLI as salvage therapy. At the time of BMT, one patient had RA, nine had RAEB, of whom three were in CR after induction-type chemotherapy, two had RAEB-T, one had CMML and one had AML. Donors were HLA-matched siblings (n=12), HLA-matched other relative (n=1) and unrelated (n=1). At the time of relapse, the median marrow blast count was 9%. The median CD3+ cell dose administered was 6.3 x 10(7)/kg. With a median follow-up of 49 months, six patients were alive, of whom two were in CR after DLI alone and remained disease-free, two were in CR after a second BMT and two had active disease. Eight patients died of disease progression. Although DLI alone seems to be effective in a small number of patients with MDS, other treatment strategies, including prior debulking chemotherapy, deserve investigation.

Acute Disease↗
PubMed2003

Hearing impairment in essential tremor.

OBJECTIVE: To assess hearing in patients with essential tremor (ET) vs patients with Parkinson disease (PD) and normal controls. METHODS: The authors assessed demographic and clinical information including use of hearing aids in 250 patients with ET, 127 patients with PD, and 127 normal controls. The authors administered the Nursing Home Hearing Handicap Index (NHHI), a validated measure of hearing disability. Regression techniques were used to adjust for factors such as age and sex. The authors assessed a complete audiologic evaluation in a subset of patients with ET. RESULTS: Patients with ET had worse adjusted NHHI scores when compared to patients with PD (p < 0.001), controls (p < 0.001), and both (p < 0.001). A higher percentage of patients with ET also used hearing aids (p < 0.0001). In the ET group, hearing loss was associated with tremor severity (p = 0.02) and tended to be associated with older age (p = 0.06), male sex (p = 0.06), and the absence of dystonia (p = 0.18). Audiology testing was consistent with high-frequency sensorineural hearing loss. Central processing was not disproportionally greater than peripheral loss. CONCLUSION: Patients with ET have increased hearing disability compared to patients with PD and normal controls, which correlates with tremor severity.

Aged↗
PubMed2003

Higher doses of CD34+ peripheral blood stem cells are associated with increased mortality from chronic graft-versus-host disease after allogeneic HLA-identical sibling transplantation.

Allogeneic peripheral blood stem cell transplantation (PBSCT) has emerged as an alternative to bone marrow transplantation. PBSCT can be associated with a higher incidence of chronic graft-versus-host disease (cGVHD). In this study, we investigated whether there was a correlation between the composition of PBSC grafts (CD34+ and CD3+ cells) and hematological recovery, GVHD, relapse, and relapse-free survival (RFS) after myeloablative HLA-identical sibling PBSCT. The evolution of 100 acute or chronic leukemia patients was analyzed. Neither hematological recovery, acute or cGVHD, nor relapse, was significantly associated with CD3+ cell dose. Increasing CD34+ stem cells was associated with faster neutrophil (P=0.03) and platelet (P=0.007) recovery. Moreover, 47 of the 78 patients evaluable for cGVHD (60%; 95% CI, 49-71%) developed extensive cGVHD. The probability of extensive cGVHD at 4 years was 34% (95% CI, 21-47%) in patients receiving a 'low' CD34+ cell dose (<8.3 x 10(6)/kg), as compared to 62% (95% CI, 48-76%) in patients receiving a 'high' CD34+ cell dose (>8.3 x 10(6)/kg) (P=0.01). At a median follow-up of 59 months, this has not translated into a difference in relapse. In patients evaluable for cGVHD, RFS was significantly higher in patients receiving a 'low' CD34+ cell dose as compared to those receiving a 'high' CD34+ cell dose (P=0.04). This difference was mainly because of a significantly higher cGVHD-associated mortality (P=0.01). Efforts to accelerate engraftment by increasing CD34+ cell dose must be counterbalanced with the risk of detrimental cGVHD.

Acute Disease↗
PubMed2002

Healthy sibling donor anxiety and pain during bone marrow or peripheral blood stem cell harvesting for allogeneic transplantation: results of a randomised study.

This study reports the first comparison of healthy donor subjective well-being during two alternative procedures of hematopoietic stem cells harvesting for allogeneic transplantation. Among the 105 donors included between September 1996 and October 1998 in the SFGM French randomised trial aiming to compare allogeneic bone marrow (BM) transplantation and blood cell (BC) transplantation, 64 donors (33 in BC and 31 in BM groups) were relevant for the analysis. They had received a set of self-administered questionnaires to complete during the collection process, aiming to measure anxiety (assessed using the Spielberger's State-Trait Anxiety Inventory) and pain induced by the procedure (evaluated using a visual analogical scale). Results showed that no harvest procedure is free from pain even if none was more painful than the other. Levels of anxiety before the collection procedure were high in both groups and significantly so for BC donors. Although BC collection induces at least similar levels of pain and anxiety as does BM collection, they were of a different kind, and the short-term impact of G-CSF stimulation on the well-being of BC donors has to be taken into account in improving quality of care in the allogeneic setting.

Adult↗
PubMed2002

Score of neonatal acute physiology as a measure of illness severity in mechanically ventilated term babies.

UNLABELLED: The objectives of this population-based, case-control cohort study were to describe the use of the score of neonatal acute physiology (SNAP) as a measure of illness severity in mechanically ventilated term infants, to compare the SNAP scores of the different diagnostic groups, to assess the contribution of the individual SNAP items to the overall SNAP severity category, and to assess SNAP as a predictor of mortality and neonatal intensive care unit (NICU) resource utilization (length of stay (LOS) and duration of ventilation (LOV)). The study was carried out in Sydney and four large rural/urban health areas in New South Wales, Australia. The subjects--182 singleton term infants with no major congenital anomalies--were admitted to a tertiary NICU for mechanical ventilation. Highest mean (SD) SNAP scores occurred in infants ventilated for meconium aspiration (18 (9)), and perinatal asphyxia (17 (9)), compared with pulmonary hypertension (14 (6)) and respiratory distress syndrome (13 (5)). The individual SNAP items that contributed most to SNAP moderate and severe categories were blood gas items, creatinine, urine output, blood glucose, and seizures. Predictors of death included total SNAP score, individual SNAP items (urine output, pH, Oxygenation Index (OI)), 5-min Apgar, gestational age >40 wk, growth restriction, and ventilation for asphyxia/apnoea. SNAP alone was not a good predictor of NICU resource utilization (LOS, LOV) in term infants. The best predictors were LOV for LOS, and a combination of SNAP and the reason for ventilation for LOV. CONCLUSION: SNAP is a useful measure of severity of illness in sick term neonates admitted to a tertiary NICU. This measure can be used to predict neonatal morbidity and mortality, and to some extent NICU resource utililization.

Health Status Indicators↗
PubMed2002

Reliability of the SNAP (score of neonatal acute physiology) data collection in mechanically ventilated term babies in New South Wales, Australia.

UNLABELLED: The aim of this population-based, case-control, cohort study was to report inter-rater reliability between the New South Wales Neonatal Intensive Care Unit Data Collection (NICUS) audit nurses' collection of SNAP (OS) and a research nurse's SNAP data as the audit SNAP (AS). The study was carried out in Sydney and four large rural/urban health areas in New South Wales (NSW), Australia. The subjects--182 singleton term infants with no major congenital anomalies--were admitted to a tertiary neonatal intensive care unit (NICU) for mechanical ventilation. SNAP data were collected on the 182 case infants, born between 1 January and 31 December 1996, by clinical audit officers in the nine tertiary NICUs in NSW. The research officer conducted an audit of the original SNAP score on all infants. The data were examined using Pearson's correlation coefficient, weighted kappa, a plot of difference in SNAP against mean SNAP and Wilcoxon's signed rank sum test. Pearson's correlation coefficient between the OS and AS data was 0.80. Median (interquartile range) SNAP was 13 (9,19) for the OS and 14 (10,20) for the AS. Weighted kappa was highest for highest heart rate, paO2, temperature (degrees C), oxygenation index, haematocrit, platelet count, lowest serum sodium, lowest blood glucose and seizure. In 17 (9%) infants, OS and AS differed by > or = 10, 14 because of an original data collection error, 1 data entry error, 1 audit error and 1 for both data collection and data entry errors. CONCLUSION: If SNAP is to be incorporated into any routine NICU data collection, it should be audited regularly on a sample of records. It is important to standardize and adhere to strict definitions for parameters before the collection of SNAP data.

Case-Control Studies↗
PubMed2001

Do very sick neonates born at term have antenatal risks? 1. Infants ventilated primarily for problems of adaptation to extra-uterine life.

AIMS: 1. Ascertain antenatal and intrapartum risk factors for term neonates ventilated primarily for 'perinatal asphyxia'. 2. Describe the neonatal morbidity and mortality. METHODS: Population-based case control cohort study. SETTING: Sydney and four large rural/urban health areas in New South Wales. SUBJECTS: Singleton term infants, no major congenital anomaly: subset of 83 infants ventilated primarily for 'asphyxia' from 182 cases admitted to a tertiary neonatal intensive care unit (NICU) for mechanical ventilation, 550 randomly selected controls. Outcome. Risk factors for case status by maternal, antenatal, labor, delivery, and combined epochs, adjusted odds ratios (OR), 95 per cent confidence intervals (CI), p < 0.05. RESULTS: Predictors of case status by multivariate epochs: Primigravida (1.8 [1.1, 2.8]), thyroid disease (7.8 [1.1, 57.0]), any antenatal complication (5.1 [3.0, 8.6]), growth restriction (4.2 [1.7, 10.4]), male gender (2.1 [1.3, 3.5]), gestational age >40 weeks (1.9 (1.1, 3.3)), prolonged rupture of membranes (9.7 [1.3, 72.5]), complicated labor (6.6 [3.7, 11.9]), induced labor (2.2 [1.3, 3.9]), prostaglandins 2.46 [1.23, 4.91]), maternal pyrexia (10.8 [2.8, 42.7]), placental hemorrhage in labor (OR 4.24 [1.45, 12.42]), forceps delivery (4.1 [1.9, 8.5]), emergency cesarean section (4.7 [2.6, 8.7]). Twenty case infants (24%) and no control infants died. CONCLUSIONS: This study has shown maternal and antepartum risk factors for severe neonatal morbidity in term infants. More centers need to become interested in the term baby, so that a larger multicenter study can further elucidate the heterogeneous causal pathways to term neonatal morbidity.

Adaptation, Biological↗
PubMed2001

Do very sick neonates born at term have antenatal risks? 2. Infants ventilated primarily for lung disease.

AIMS: 1. Ascertain antenatal and intrapartum risk factors for term neonates ventilated primarily for respiratory problems. 2. Describe the neonatal morbidity and mortality. METHODS: Population-based case control cohort study. SETTING: Sydney and four large rural/urban Health Areas in New South Wales, 1996. SUBJECTS: Singleton term infants, no major congenital anomaly: subset of 99 infants ventilated primarily for respiratory problems from 182 cases admitted to a tertiary neonatal intensive care unit (NICU) for mechanical ventilation, and 550 randomly selected controls. OUTCOME: Risk factors for case status by maternal, antenatal, labor, delivery, and combined epochs, adjusted Odds Ratios (OR), 95 per cent Confidence Intervals (CI), p<0.05. RESULTS: Predictors of case status by multivariate epochs: mother's age > or =35 years (1.9 (1.1, 3.2) p=0.03), primigravida (1.8 (1.1, 2.8) p=0.01), any antenatal complication (3.8 (2.4, 5.9) p=0.0001), birth weight < 3rd percentile (3.7 (1.5, 9.1) p=0.006), gestational diabetes (2.9 (1.3, 6.9) p=0.01), maternal pyrexia (6.5 (1.6, 27.2) p=0.01), birth weight >90th percentile (1.8 (1.01, 3.2) p=0.047), gestation 37-38 weeks (2.3 (1.5, 3.6) p=0.0004), forceps (4.4 (2.1, 9.1) p=0.0001), elective cesarean section (3.7 (2.0, 6.5) p=0.0001), emergency cesarean section (4.5 (2.4, 8.4) p=0.0001). Case mortality rate was 5 per cent. CONCLUSION: The pathways to neonatal respiratory morbidity in term infants are multifactorial. Several areas which warrant more in-depth study are: elective cesarean section at 37-38 weeks gestation, fetal growth restriction, macrosomia and the pattern of in-utero growth, maternal weight gain during pregnancy, gestational diabetes, pyrexia in labor and the role of chorioamnionitis.

Adult↗
PubMed2001

Acute myeloid leukaemia in human immunodeficiency virus-infected adults: epidemiology, treatment feasibility and outcome.

The epidemiology and clinical outcome of acute myeloid leukaemia in human immunodeficiency virus (HIV)-infected adults is poorly documented. We retrospectively surveyed all French haematology centres for adult acute myeloid leukaemia (AML) cases diagnosed between January 1990 and July 1996 who were found to be HIV-seropositive before or at the time of AML diagnosis. Medical charts were reviewed to determine the stage of HIV infection, the characteristics of AML and the response of AML to chemotherapy. Sixteen cases of AML (13 men, three women) were reported by 12 haematology units. Based on assumptions on the size, age and sex distribution of the HIV-infected population in France, the estimated risk of AML in 1990 to 1996 among HIV-infected adults was twice that of the general population (standardized incidence ratio = 2.05; 95% confidence interval, 1.17-3.34). Two other cases occurring before 1990 were spontaneously notified to the authors and were included in the clinical analysis. At AML diagnosis, the median CD4+ cell count was 275 x 106/l and nine patients had acquired immune deficiency syndrome (AIDS). Fifteen patients were scheduled for remission-induction therapy of AML. No deaths were related to AML treatment. Complete remission was obtained in 11 out of 15 patients. Three patients were long-term survivors: two remain alive in complete remission at 8 years and 9 years, respectively, and the third died of AIDS at 8 years. A CD4+ cell count above 200 x 106/l at AML diagnosis was predictive of longer survival (log-rank test: P = 0.004). Like many other malignancies, the incidence of AML appears to be increased in HIV-infected patients. Our results show a twofold higher incidence, although this needs to be confirmed in a specifically designed prospective epidemiological study. Such patients, especially those with CD4+ cell counts above 200 x 106/l at AML diagnosis, should receive remission-induction therapy, which can confer long-term survival.

Acute Disease↗
PubMed2001

Enhanced activation of B cells in a granulocyte colony-stimulating factor-mobilized peripheral blood stem cell graft.

In a randomized study that compared human leucocyte antigen-identical allogeneic granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cell (PBSC) versus bone marrow (BM) transplantation, the expression of activation markers, CD23, CD25 and CD45RO by B cells, was compared in blood before and after G-CSF mobilization and in PBSC versus BM grafts. The fractions of CD23+ and CD25+ B cells were higher in PBSC than in BM grafts. Moreover, we observed a G-CSF-induced increase in B-cell fractions in blood as well as in PBSC grafts when compared with BM grafts. Such an enhanced B-cell activation could contribute to the accelerated kinetics of immuno-haematological reconstitution, the occurrence of acute haemolysis in the ABO minor incompatibility setting, as well as the increased incidence of chronic graft-versus-host disease observed after PBSC transplantation.

B-Lymphocytes↗
PubMed2001

Azone enhances clinical effectiveness of an optimized formulation of triamcinolone acetonide in atopic dermatitis.

BACKGROUND: Atopic dermatitis is a chronic, relapsing condition affecting up to 14% of the population in Western countries. Topical corticosteroids are the mainstay of treatment. Triamcinolone acetonide, a corticoid of intermediate potency, has proven useful in the treatment of atopic dermatitis. AIM: To evaluate the effectiveness of a triamcinolone acetonide-laurocapram combination in the treatment of atopic dermatitis. METHODS: One hundred and fifty patients were enrolled in a three-arm, parallel group, controlled clinical trial evaluating the effectiveness of a triamcinolone acetonide (0.05%) and laurocapram combination, applied twice daily for 2 weeks, in the treatment of atopic dermatitis. Fifty patients received triamcinolone acetonide-laurocapram (TNX), 50 triamcinolone acetonide (TN), and 50 a vehicle control formulation (AN). Response to treatment was evaluated by change in disease severity at 6 h, at 3, 8, and 15 days after the start of treatment, and by the global change in disease status. RESULTS: TNX effected a significantly higher degree of improvement in the signs and symptoms of atopic dermatitis (erythema, induration, and pruritus) and a greater overall improvement in disease status compared with treatment with TN or AN. Treatment-associated side-effects were local reactions, occurring in three, two, and six patients in the TNX, TN, and AN groups, respectively. CONCLUSIONS: The results suggest that the incorporation of laurocapram in the formulation enhances the effectiveness of triamcinolone acetonide, without compromising its safety profile.

Anti-Inflammatory Agents↗
PubMed2001

Decreased cyclin B1 expression contributes to G2 delay in human brain tumor cells after treatment with camptothecin.

DNA damage produces delayed mitosis (G2/M delay) in proliferating cells, and shortening the delay sensitizes human malignant glioma and medulloblastoma cells to cytotoxic chemotherapy. Although activation of the cyclin-dependent kinase CDC2 mediates G2/M transition in all tumor cells studied to date, regulation of CDC2 varies between tumor types. Persistent hyperphosphorylation of kinase and reduced cyclin expression have been implicated as mediators of treatment-induced G2 delay in different tumor models. To evaluate regulation of G2/M transition in human brain tumors, we studied the expression and/or activity of CDC2 kinase and cyclins A and B1 in U-251 MG and DAOY medulloblastoma cells after their treatment with camptothecin (CPT). Synchronized cells were treated during S phase, then harvested at predetermined intervals for evaluation of cell cycle kinetics, kinase activity mRNA, and protein expression. CPT produced G2 delay associated with decreased CDC2 kinase activity and cyclin B1 expression. Kinase activity was associated with CDC2 bound to cyclin B1, not cyclin A, in both cell lines. Cyclin A mRNA and protein expression were reduced after CPT treatment; however, decreased protein expression was short lived and moderate in the glioma and primitive neuroectodermal tumor/medulloblastoma cells, respectively. We conclude that G2 delay is a common response of brain tumor cells to chemotherapy with topoisomerase I inhibitors and that a mechanism of this delay may be reduced expression of cyclin B1.

Antineoplastic Agents, Phytogenic↗