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Biomedical subjects

D Curran

Publications and source records attributed to D Curran.

At least 37 records · Page 2Linked to original sources
PubMed1999

Quality-adjusted survival (Q-TWiST) analysis of EORTC trial 30853: comparing goserelin acetate and flutamide with bilateral orchiectomy in patients with metastatic prostate cancer. European Organization for Research and Treatment of Cancer.

BACKGROUND: The first data analysis of the European Organization for Research and Treatment of Cancer (EORTC) 30853 trial indicated a significantly longer time to progression and duration of survival for the maximal androgen blockade (MAB) treatment arm. However, the MAB treatment arm had a higher frequency of reported side effects. METHODS: The quality-adjusted survival (Q-TWiST) method was applied to perform a secondary analysis of the EORTC 30853 trial in order to obtain a quality-adjusted survival (QAS) analysis. Two models with different definitions of the progression health state were used for the analysis. In the first model, progression was defined by both objective and subjective criteria, and in the second model only by increase in pain score. The approach was also extended to include an analysis using actual utility scores (Q-tility) of patients in the relevant health states. RESULTS: Based on Q-tility scores obtained from a separate study of a cohort of prostate cancer patients, the QAS analysis resulted in a 5.2-month difference (95% CI, -1.1; 11.5 months) in favor of zoladex and flutamide, equal in magnitude to the benefit found in the unadjusted survival analysis. CONCLUSIONS: A QAS analysis such as the Q-TWiST method may be preferred over the unadjusted approach in clinical trials where the health states are clearly distinct, and differ significantly in either duration or quality of life (QOL), or both. The second model, with progression defined as increase in pain score, made no difference to the results in this study because of the small difference in duration of the pain-progression health state between treatment arms. However, Q-tility scores from the separate cross-sectional study that was used in this Q-TWiST analysis showed that a subjective definition of health states better reflects differences in QOL between the health states that the patients experience during follow-up.

Antineoplastic Agents, Hormonal↗
PubMed1999

Cisplatin (P), vinblastine (V) and bleomycin (B) combination chemotherapy in recurrent or advanced granulosa(-theca) cell tumours of the ovary. An EORTC Gynaecological Cancer Cooperative Group study.

The aim of this study was to investigate the clinical activity and toxicity of a modified PVB regimen (cisplatin, vinblastine and bleomycin) in patients with advanced or recurrent, pure granulosa cell tumours (GCTs) or mixed granulosa-theca cell tumours (GTCTs). The PVB regimen consisted of cisplatin (P) 20 mg/m2 intravenous (i.v.) days 1-5, vinblastine (V) 0.15 mg/kg i.v. days 1-2 and bleomycin (B) 30 mg i.v. on day 2, and 15 mg on day 15, for 28 days. 38 eligible patients were entered in this trial. Prior to PVB all patients underwent surgery and 13 received postoperative radio- or other prior chemotherapy. The median number of PVB cycles was 4 in both groups. In the group of 25 patients who had received prior surgery only, 7 and 6 patients had complete and partial responses, respectively (response rate: 52%, 95% confidence limits: 31.3-72.2%). At a median follow-up of 39 months, 6 patients were alive with no evidence of disease, 6 were alive with disease, 12 died due to malignant disease and 1 died due to intercurrent disease. The median time to progression was 13.9 months. The median survival was 25.4 months. 3-year survival was 49% (95% confidence limits: 29-69%). In the group of 13 patients who had previously received postoperative radio- or chemotherapy, 5 complete and 5 partial responses were observed on PVB (response rate: 77%, 95% confidence limit: 46.2-95.0%). At a median follow-up of 50 months, 6 patients were still alive, only 1 without evidence of disease, 6 died due to malignant disease and 1 died due to intercurrent disease. The median time to progression was 19.3 months. The median duration of survival was 41.1 months. Accompanying toxicity was distributed in a similar pattern for both groups. Severe toxicity was mainly documented as haematological toxicity, nausea/vomiting and alopecia. Furthermore cisplatin-related peripheral neurotoxicity and mild/moderate signs of bleomycin-related pulmonary toxicity were observed. The present data confirm the therapeutic activity of the PVB regimen in advanced/recurrent GCTs. The response rate was moderately high compared with previous studies, with a median duration of response of 20 months for both groups.

Adult↗
PubMed1999

Sample size estimation in phase III cancer clinical trials.

This paper deals with the basic principles involved in sample size calculation of phase III cancer clinical trials. It illustrates the concepts and factors determining the sample size. Various examples of phase III cancer clinical trials are provided and the sample size is calculated taking into account the assumptions made. The examples provided include sample sizes for comparing proportions and sample sizes for comparing survival times. Several special topics are also discussed including choice of endpoint, number of treatment groups, factorial designs and equivalence trials.

Clinical Trials, Phase III as Topic↗
PubMed1998

Adjuvant portal-vein infusion of fluorouracil and heparin in colorectal cancer: a randomised trial. European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group, the Gruppo Interdisciplinare Valutazione Interventi in Oncologia, and the Japanese Foundation for Cancer Research.

BACKGROUND: There is conflicting evidence on the efficacy of regional adjuvant chemotherapy, via portal-vein infusion (PVI), after resection of colorectal cancer. We undertook a randomised controlled multicentre trial to investigate the efficacy of PVI (500 mg/m2 fluorouracil plus 5000 IU heparin daily for 7 days). METHODS: 1235 of about 1500 potentially eligible patients were randomly assigned surgery plus PVI or surgery alone (control). The patients were followed up for a median of 63 months, with yearly screening for recurrent disease. The primary endpoint was survival; analyses were by intention to treat. FINDINGS: 619 patients in the control group and 616 in the PVI group met eligibility criteria. 164 (26%) control-group patients and 173 (28%) PVI-group patients died. 5-year survival did not differ significantly between the groups (73 vs 72%; 95% Cl for difference -6 to 4). The control and PVI groups were also similar in terms of disease-free survival at 5 years (67 vs 65%) and the number of patients with liver metastases (79 vs 77%). INTERPRETATION: PVI of fluorouracil, at a dose of 500 mg/m2 for 7 days, cannot be recommended as the sole adjuvant treatment for high-risk colorectal cancer after complete surgical excision. However, these results cannot eliminate a small benefit when PVI is used at a higher dosage or in combination with mitomycin.

Aged↗
PubMed1998

Brain-only metastases of small cell lung cancer; efficacy of whole brain radiotherapy. An EORTC phase II study.

BACKGROUND AND PURPOSE: To evaluate the efficacy of WBRT as a single treatment modality in patients with brain metastases of small cell lung cancer. PATIENTS AND METHODS: The patients had brain metastases of small cell lung cancer without any sign of tumour outside the brain and were treated with 10 x 3.0 Gy WBRT. Response and neurological functions were evaluated after 6, 18 and 36 weeks. RESULTS: Twenty of 22 eligible patients were evaluable for response. In six patients a complete response was seen and in five patients a partial response was seen giving a response rate of 50% (95% CI 28-72%). Response duration was 5.4 months (range 63-260 days) and median survival was 4.7 months (range 14-743 days). In the majority of patients the first site of progression after WBRT was in the central nervous system. Twelve of the patients had stabilization or improvement of the neurological function. CONCLUSION: WBRT for brain metastases of small cell lung cancer gives a 50% response rate with stabilization or improvement of neurological function. Response duration and survival are short.

Adult↗
PubMed1998

Quality of life of early-stage breast cancer patients treated with radical mastectomy or breast-conserving procedures: results of EORTC Trial 10801. The European Organization for Research and Treatment of Cancer (EORTC), Breast Cancer Co-operative Group (BCCG).

In 1980 the EORTC-BCCG initiated a multicentre randomised clinical trial comparing modified radical mastectomy (MRM) with breast-conserving therapy (BCT) in stage I and II breast cancer. The main endpoint of the trial was survival. A brief quality of life (QoL) questionnaire consisting of two multi-item scales (body image and fear of recurrence) and two single items (satisfaction with treatment and cosmetic result) was included in the trial. A cosmetic evaluation of the breast after conservative surgery was also performed. This report concentrates on the results of the QoL study and the cosmetic evaluation. Multitrait scaling analysis was employed to verify the hypothesised scale structure of the questionnaire. Treatment comparison of the QoL scores at 2 years post-treatment was performed using a stratified Wilcoxon rank sum test. Both patients' and doctors' ratings of the cosmetic result were documented on the clinical follow-up form. A multivariate analysis was performed to identify which factors influenced the cosmetic outcome. In total, 127 patients in the MRM arm and 151 in the BCT arm completed a QoL questionnaire at approximately 2 years after randomisation (months 25-36). The Cronbach's alpha coefficients were 0.79 and 0.73 for the body image and fear of recurrence scales, respectively. Significant benefit in body image and satisfaction with treatment was observed in the BCT patients. No significant difference was observed in fear of recurrence between the two groups. Ratings of cosmetic results decreased with time, in line with clinical observations of long-term side-effects of radiotherapy. Wide excision appeared to be the most important predictive factor for poor cosmetic result. In this multicentre randomised study, BCT helped to maintain the patients' body image, resulted in higher satisfaction with treatment and yielded no significant difference from MRM with respect to fear of recurrence.

Adult↗
PubMed1998

Quality of life after radiation therapy of cerebral low-grade gliomas of the adult: results of a randomised phase III trial on dose response (EORTC trial 22844). EORTC Radiotherapy Co-operative Group.

In 1985, the EORTC Radiotherapy Co-operative Group launched a randomised phase III study comparing high-dose (59.4 Gy in 6.5 weeks) versus low-dose (45 Gy in 5 weeks) radiotherapy with conventional techniques in patients diagnosed with low-grade cerebral glioma. The primary endpoint of the study was survival. No difference in survival was observed between the two treatment strategies. A quality of life (QoL) questionnaire consisting of 47 items assessing a range of physical, psychological, social, and symptom domains was included in the trial to measure the impact of treatment over time. Patients who received high-dose radiotherapy tended to report lower levels of functioning and more symptom burden following completion of radiotherapy. These group differences were statistically significant for fatigue/malaise and insomnia immediately after radiotherapy and in leisure time and emotional functioning at 7-15 months after randomisation. These findings suggest that for conventional radiotherapy for low-grade cerebral glioma, a schedule of 45 Gy in 5 weeks not only saves valuable resources, but also spares patients a prolonged treatment at no loss of clinical efficacy.

Adult↗
PubMed1998

Prognostic factors in patients with pleural mesothelioma: the European Organization for Research and Treatment of Cancer experience.

PURPOSE: Identification of prognostic factors in patients with malignant pleural mesothelioma based on prospectively collected international data. PATIENTS AND METHODS: From October 1984 to October 1993, 204 eligible adult patients with malignant pleural mesothelioma were entered into five consecutive prospective European Organization for Research and Treatment of Cancer (EORTC) phase II clinical trials designed to assess the efficacy of various anticancer drugs (mitoxantrone, epidoxorubicin, etoposide, and paclitaxel). The Cox model was used to assess 13 factors related to biology and disease history with respect to survival. RESULTS: The median survival duration was 12.6 months from diagnosis and 8.4 months from trial entry. In the multivariate analysis, poor prognosis was associated with a poor performance status, a high WBC count, a probable/possible histologic diagnosis of mesothelioma, male gender, and having sarcomatous tissue as the histologic subtype. Taking these five factors into consideration, patients were classified into two groups: a good-prognosis group (1-year survival rate, 40%; 95% confidence interval [CI], 30% to 50%) and a poor-prognosis group (1-year survival, 12%; 95% CI, 4% to 20%). CONCLUSION: These results may help to design new clinical trials in pleural mesothelioma by selecting more homogenous groups of patients.

Age Factors↗
PubMed1998

Randomized study of paclitaxel-cisplatin versus cisplatin-teniposide in patients with advanced non-small-cell lung cancer. The European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.

PURPOSE: To compare two cisplatin based chemotherapy schedules in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 332 patients with advanced NSCLC were randomized to receive cisplatin 80 mg/m2 on day 1 either in combination with teniposide 100 mg/m2 on days 1, 3, and 5 (arm A) or paclitaxel 175 mg/m2 by 3-hour infusion on day 1 (arm B); cycles were repeated every 3 weeks. RESULTS: Fifteen patients were ineligible; patient characteristics were well balanced between the two arms: 71% were male, 71% had less than 5% weight loss, 89% had a World Health Organization (WHO) performance status of 0 to 1, 51% had adenocarcinoma, and 61% had stage IV disease. Hematologic toxicity was significantly more severe in arm A (leukopenia, neutropenia, and thrombocytopenia grade 3 or 4: 66% v 19%, 83% v 55%, 36% v 2% in arms A and B, respectively), which resulted in more febrile neutropenia (27% v 3% in arms A and B, respectively), dose reductions, and treatment delays. There were a total of nine toxic deaths, six due to neutropenic sepsis: five in arm A and one in arm B. In contrast, arthralgia/myalgia (grade 2 or 3, 4% v 17%), peripheral neurotoxicity (grade 2 or 3, 6% v 29%), and hypersensitivity reactions (1% v 7%, all grades) were significantly more frequent in arm B. The frequency and severity of other toxicities were comparable between the two arms. Responses were one complete and 44 partial on arm A (28%) and two complete and 61 partial (41%) on arm B (P = .018). There was no significant difference in survival, with median and 1-year survivals 9.9 versus 9.7 months and 41% versus 43%, respectively in arm A and B. Progression-free survival was 4.9 and 5.4 months in arm A and B, respectively. Selected centers participated in a quality-of-life (QoL) assessment, which was performed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and LC-13 administered at baseline and every 6 weeks thereafter. Arm B achieved a better score at week 6 for emotional, cognitive and social functioning, global health status, fatigue, and appetite loss, which was lost at 12 weeks. In conclusion, arm B appears superior to arm A with regard to response rate, side effects, and QoL. CONCLUSION: Although survival was not improved, arm B offers a better palliation for advanced NSCLC patients than arm A.

Adult↗
PubMed1997

Final results of a phase III clinical trial on adjuvant intraportal infusion with heparin and 5-fluorouracil (5-FU) in resectable colon cancer (EORTC GITCCG 1983-1987). European Organization for Research and Treatment of Cancer. Gastrointestinal Tract Cancer Cooperative Group.

In this phase III clinical trial conducted by the Gastrointestinal Tract Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer (GITCCG-EORTC), we evaluated the effect of adjuvant intraportal infusion of heparin (HEP) and 5-fluorouracil (5-FU) on overall survival, disease-free survival and time to progression in patients with resectable colon cancer. From January 1983 to June 1987, 235 patients were randomised from 14 institutions in seven European countries: 79 patients made up the control group (control): 72 the portal vein infusion group given heparin alone (5000 IU daily x 7 consecutive days) (HEP); 84 the portal vein infusion group given heparin (5000 IU daily x 7 consecutive days) and 5-FU (500 mg/m2 daily x 7 consecutive days) (HEP/5-FU); 34 patients were considered ineligible. The 199 patients considered eligible were well balanced for age, sex, Karnofsky index, tumour location, surgery, surgical procedure and Dukes' stage. Four patients (2 control, 1 HEP, 1 HEP/5-FU) died of surgical complications. No differences were observed between control group and treatment groups (HEP, HEP/5-FU) for postoperative complications and number of hospitalisation days. Severe toxicity (grade 3-4, WHO) was found in 12% of patients in the HEP group and 8% in the HEP/5-FU group. After a median follow-up of 9 years, disease progression was reported in 40% of patients in the control group, 40% in the HEP group and 29% in the HEP/5-FU group. Five-year survival, time to progression and disease-free survival were 69%, 58% and 56%, respectively, in the control arm, 61%, 58% and 56% in the HEP arm, and 71%, 69% and 65% in the HEP/5-FU arm. Based on all randomised patients, the effect of treatment was not statistically significant with respect to any of the endpoints. It is confirmed that intraportal 5-FU infusion is safe and has a tolerable toxicity, but cannot be considered standard treatment for patients with resectable colon cancer.

Adult↗
PubMed1997

Phase II study of weekly 4'-epidoxorubicin in patients with metastatic adenocarcinoma of the cervix: an EORTC Gynaecological Cancer Cooperative Group study.

In this study 22 patients with metastatic adenocarcinoma of the cervix were treated with a weekly bolus injection of 4'-epidoxorubicin at a dose of 12 mg/m2. Seventeen patients had received prior radiotherapy, all patients were chemo-naive. Toxicity was generally absent or very mild. One patient had a complete response and 2 patients had a partial response, one was an unconfirmed partial response, giving a response rate of 14%. Six patients had stable disease. The median progression-free survival and overall survival was 2.8 months and 6.1 months, respectively. In conclusion, 4'-epidoxorubicin used at this dosage and schedule has minimal activity in metastatic adenocarcinoma of the cervix.

Adenocarcinoma↗
PubMed1997

Baseline quality of life of patients with advanced prostate cancer. European Organization for Research and Treatment of Cancer (EORTC), Genito-Urinary Tract Cancer Cooperative Group (GUT-CCG)

Quality of life (QoL) is now commonly studied in prostate cancer. However, little is known about the appropriateness of the various QoL instruments in this group of patients. The purpose of this work was to study the baseline QoL assessment of patients with prostate cancer who were randomised into three EORTC phase III studies. The three trials included locoregional prostate cancer patients, poor prognosis metastatic patients and hormone resistance patients, respectively. In the three trials, patients were asked to complete a questionnaire assessing their physical and psychosocial functioning and their symptom levels. These questionnaires included questions from the EORTC QLQ-C30 (version 1): the physical functioning, role functioning, global health/QoL scales and a single pain item. The psychometric properties of the scales were assessed and an analysis was performed to investigate if differences existed in the scale scores between the three groups of patients, 638 baseline questionnaires were available for patients entered into the three trials. The Gutman coefficients of reproducibility and scalability were 0.94 and 0.71, respectively, for the physical functioning scale and 0.97 and 0.90, respectively, for the role functioning scale. The Cronbach's alpha reliability coefficients were 0.68, 0.48 and 0.90 for the physical functioning, role functioning and global health/QoL scales, respectively. The four scales were able to distinguish clearly between the patient populations under study. The physical functioning, role functioning, global health/QoL scales and the single pain item scale from the EORTC QLQ-C30 (version 1) are valid measures when used in the setting of prostate cancer.

Activities of Daily Living↗
PubMed1996

Results of a phase II trial of epirubicin and cisplatin (EP) before and after irradiation and 5-fluorouracil in locally advanced pancreatic cancer: an EORTC GITCCG study.

The objective of the present study was to define the role of chemotherapy, in the form of the EP regimen, consisting of epirubicin (E) and cisplatin (P) in addition to irradiation in combination with 5-fluorouracil (5-FU) for treatment of pancreatic cancer. 53 eligible patients with histologically or cytologically proven locally advanced pancreatic cancer were treated with three cycles of E 60 mg/m2 (if this dose was well tolerated then the dose of E was increased by 10 mg/m2 in the next cycle; 80 mg/m2 was the maximum dose for the following cycles) and P 100 mg/m2 once every 3 weeks, followed after 4 weeks by a split course of irradiation of 40 Gy with 5-FU 500 mg/m2 on each of the first 3 days of each 20 Gy treatment segment. This was followed by another three cycles of EP in patients who achieved stable disease (SD) or a better response after the first three cycles. The treatment given with standard anti-emetics was moderately tolerated. The chemotherapy related toxicity consisted mainly of myelosuppression and the chemoradiotherapy related toxicity of gastrointestinal side-effects. However, due to the long duration of treatment which made the whole treatment difficult to endure, only 18/53 (34%) actually completed the full treatment regimen. Responses were evaluated after the first three cycles and 4 weeks after the completion of the treatment by serial CT-scans using standard criteria. The results in 53 evaluable patients after the first three cycles of EP were as follows: 1 patient achieved a clinical complete response (CR), 7 a partial response (PR) (CR + PR: 15%; 95% confidence interval (CI): 11-33%), 36 patients (68%) had stable disease (SD) and 6 patients progressive disease (PD). There was 1 early PD, 1 toxic death and 1 patient could not be evaluated. The response at the end of the treatment was 3 CR, 11 PR (CR + PR: 14/53 (26%); 95% CI: 15-40%), 30 SD and 6 PD. The median time to progression was 8.9 months and the median duration of response 13.1 months. The median survival of all treated patients was 10.8 months (range 7 days to 41.5 months), of responders 15.1 months and, of the patients with SD 10.3 months. These results are comparable to other combined modality regimens reported in the literature for locally advanced disease. The addition of the systemic treatment with E and P offers no additional advantage to combined modality treatment alone.

Adenocarcinoma↗
PubMed1996

Standard versus alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: an EORTC Phase III trial.

Alternating chemotherapy for small cell lung cancer has been tested in several studies. Some have shown positive results that have not been confirmed in other studies. In all of the studies, however, the degree of non-cross-resistance in the regimens was questionable. The EORTC Lung Cancer Study Group developed two equipotent regimens: (i) standard (CDE)-cyclophosphamide, doxorubicin, etoposide; (ii) (VIMP)-vincristine, carboplatin, ifosfamide, mesna, both non-cross-resistance. These two combinations were alternated and compared with the standard chemotherapy regimen in a group of 143 patients with extensive small cell lung cancer. Median survival was 7.6 months in the standard arm and 8.7 in the alternating arm (P = 0.243). Median time to progression was 5.8 and 6.4 months, respectively (P = 0.166). Median response duration was 7.0 and 6.8 months (P = 0.221). The use of two alternating regimens with a proven degree of non-cross-resistance did not result in any improvement in survival in patients with extensive small cell lung cancer.

Adult↗
PubMed1990

The effects of gamma-interferon on human peripheral blood monocyte/macrophage-mediated bone particle degradation.

gamma-Interferon (IFN-gamma) has recently been demonstrated to inhibit the ability of mononuclear phagocytes to degrade bone particles. We have further addressed the specificity, potency and mechanism of this activity using human recombinant IFN-gamma. Adherent peripheral blood mononuclear leukocytes from normal human volunteers were cultured with washed, sieved (less than or equal to 75 microns) 45Ca-labelled rat bone particles for 3 days, after which bone particle degradation (7.1 +/- 1.6%, n = 11) was calculated from the fraction of 45Ca released into the medium. As little as 5 U/ml IFN-gamma significantly suppressed bone particle degradation and 50 U/ml was associated with consistent marked suppression (74.0 +/- 3.5% inhibition, P less than 0.001, n = 11). IFN-gamma was not suppressive if added to cells 24 h or more after exposure to bone particles. Addition of indomethacin (10 microM) did not reverse the effect of IFN-gamma, suggesting that it was not prostaglandin-mediated. In addition, 1,25(OH)2D3 (10 nM) did not remove the inhibitory effect of IFN-gamma. Contact of mononuclear phagocytes with bone particles and secretion of soluble factors from these cells have both been demonstrated to play a role in their ability to degrade bone particles. IFN-gamma (50 U/ml) inhibited monocyte/macrophage interaction with another unopsonized surface, i.e., one micron fluorescent latex particles, decreasing the number of internalized particles from 12.6 +/- 2.9 per cell to 5.9 +/- 1.4 per cell (P less than 0.01, n = 15), as measured using flow cytometry. However, binding of bone particles by the cells was not diminished by IFN-gamma. Exogenous alpha-interferon and human recombinant IL-1 beta, TNF-alpha, and lymphotoxin did not alter bone particle degradation. In addition, endogenous IL-1 beta release from human monocyte/macrophages exposed to bone particles was negligible and unaffected by IFN-gamma. We conclude that IFN-gamma is a potent and specific inhibitor of monocyte/macrophage-mediated bone particle degradation, and that this activity does not appear to be due to effects on the ability of monocytes to bind bone particles or to release IL-1 in response to the particles.

Animals↗
PubMed1987

Characterization of a human osteoblastic osteosarcoma cell line (SAOS-2) with high bone alkaline phosphatase activity.

We characterized the alkaline phosphatase activity of the human osteogenic sarcoma cell line, SAOS-2, and studied the regulation of this enzyme and 3',5'-cyclic adenosine monophosphate levels by 1,25-dihydroxyvitamin D3 and triamcinolone acetonide. We report that the basal alkaline phosphatase activity of SAOS-2 cells was 100-1000 times greater than that of other established human osteogenic sarcoma cell lines. The enzymatic activity was thermolabile, could be inhibited by levamisole and L-homoarginine, but not by L-phenylalanine, and was immunoprecipitable with anti-bone/liver/kidney, but not with anti-placental antibody, confirming that it is the tissue-unspecific or bone/liver/kidney isoenzyme. However, in contrast to other established human osteosarcoma cell lines (TE-85, SAOS-1), in which alkaline phosphatase activity is stimulated several-fold by the steroid hormones 1,25-dihydroxyvitamin D3 and hydrocortisone, the alkaline phosphatase activity of SAOS-2 cells was not affected by 1,25-dihydroxyvitamin D3 treatment despite the presence of classical receptors for this hormone. Furthermore, administration of the potent glucocorticoid analogue, triamcinolone acetonide, induced only a modest increase in activity. The SAOS-2 cell line expressed low basal cAMP levels (28 pmol/10(6) cells) which could be increased 25-40 times by pretreatment with parathyroid hormone. However, unlike other osteoblastic models, in which PTH-induced cAMP stimulation is modulated by 1,25-dihydroxyvitamin D3 and glucocorticoids, neither of these hormones had an effect on the PTH-stimulated cAMP levels in SAOS-2 cells. We conclude that the SAOS-2 cell line is an osteoblastic cell model which expresses high levels of tissue-unspecific alkaline phosphatase activity and exhibits limited responsiveness to two steroid hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗