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Biomedical subjects

R Oosterom

Publications and source records attributed to R Oosterom.

At least 37 records · Page 2Linked to original sources
PubMed1989

Neuron-specific enolase can be used as the sole guide to treat small-cell lung cancer patients in common clinical practice.

Serum samples were collected from 115 small-cell lung cancer patients before each course of chemotherapy and during follow-up. Levels of neuron-specific enolase (NSE) were measured and compared to the clinical assessments of the course of the disease, which were done by the responsible physician without knowledge of NSE-values. The predictive accuracy of an increase or decrease of NSE for a major response (CR + PR), SD or PD was 98%. Importantly no false-positive rises of NSE were observed. On the basis of this large number of data it seems justified to conclude that in common clinical practice the treatment of small-cell lung cancer patients can be monitored by serial measurements of NSE alone.

Biomarkers, Tumor↗
PubMed1989

Combined measurements of plasma aromatic L-amino acid decarboxylase and DOPA as tumour markers in diagnosis and follow-up of neuroblastoma.

As neuroblastoma, the most common solid tumour in childhood, may contain all the constituents of the catecholamine biosynthesis cascade, some of these constituents may be produced in excess in a varying mixture reflecting the wide variability in expression of differentiated features of the tumour. We have measured plasma levels of norepinephrine (NE), epinephrine (E), dopamine (DA) and 3,4-dihydroxyphenylalanine (DOPA), and plasma activities of dopamine beta-hydroxylase (DBH) and aromatic L-amino acid decarboxylase (ALAAD) in 18 patients with neuroblastoma, in 13 at various times during the course of their disease. Activities of serum lactic dehydrogenase (LDH), serum levels of ferritin (FER) and neuron-specific enolase (NSE), and urinary vanilmandelic acid (VMA) were also determined. NE, E and DBH were found not to reflect tumour activity. In untreated active neuroblastoma DOPA or ALAAD (10 out of 10) or both (six out of 10) were clearly elevated. In all 13 patients where samples were obtained during chemotherapy, ALAAD activities fell within the normal range, while DOPA decreased more slowly. During relapse, DOPA and, especially, ALAAD, rapidly increased; in all six patients who had a relapse both DOPA and ALAAD were elevated. In complete remission (eight patients), ALAAD was normal in all patients, but DOPA remained elevated in the one patient who later experienced a relapse. Our preliminary conclusion is that combined measurements of plasma ALAAD and DOPA may be useful markers for neuroblastoma activity at diagnosis, but even more so in indicating residual disease (DOPA) and in the early detection of relapse (ALAAD).

Aromatic-L-Amino-Acid Decarboxylases↗
PubMed1989

Evaluation of prostate-specific antigen in untreated prostatic carcinoma.

A study was performed on 290 men to compare the level of serum prostate-specific antigen (PSA) in controls, patients with benign prostatic hyperplasia (BPH) and patients with prostatic cancer. The upper limit of normal was 5.0 micrograms/l as determined in 110 elderly hospitalized males (mean age 62 years) without urological complaints. Of the 106 patients with BPH, 33% had raised values above 5.0 micrograms/l. Values above 10 micrograms/l were found in 18 BPH patients. A positive correlation was found between prostate volume (grams of tissue removed during transurethral resection) and preoperative PSA levels (r = 0.55, n = 106, p less than 0.001). PSA levels above 10 micrograms/l were found in 4% of BPH patients with a prostate volume of less than 20 g (n = 54), in contrast with 45% of patients with a prostate volume above 40 g (n = 20). The sensitivity of this PSA assay (cutoff level 10 micrograms/l) as established in 74 prostate carcinoma patients was 31% for category T0 (n = 13), 56% for category T1-2 (n = 16), 75% for category T3-4 (n = 20) and 100% for category M1 or N1-4 (n = 25). In an earlier study prostatic acid phosphatase (PAP) was measured in these same samples. PSA appeared to be much more sensitive than PAP. Seventeen of the 74 prostatic carcinoma patients (23%) had normal PAP levels but their PSA values were raised above 10 micrograms/l, while in only 2 patients an increased PAP level was combined with a normal PSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗
PubMed1988

Levels of neuron-specific enolase after chemotherapy do not predict a response in small cell lung cancer.

Neuron-specific enolase (NSE) was measured in serum samples of 35 patients with small cell lung cancer and 10 control patients. The samples were collected during 10 days after the first course of chemotherapy, in order to investigate whether changes of NSE had a predictive value of tumour response. Three patterns of change of NSE were observed. Pattern 1 showed an increase of serum NSE with a maximum value more than 1.5 times the pretreatment level (n = 17); pattern 2 involved no increase at all or less than 1.5 times the pretreatment level (n = 14); pattern 3 showed a continuous decrease (n = 5). No relationship between the three patterns of change and the tumour response was observed. Only an NSE level less than 10 ng/ml at the time of start of the second course predicted a major response.

Carcinoma, Small Cell↗
PubMed1987

Studies on insulin secretion by monolayer cultures of normal and tumorous human pancreatic cells. Effects of glucose, somatostatin and SMS 201-995.

Recently, somatostatin analogs have been introduced which can be used clinically in the treatment of tumorous or functional hypoglycemia. In the present study we investigated in vitro the regulation, the degree of autonomy and the sensitivity to natural somatostatin and its analog SMS 201-995 of insulin secretion by monolayer cultures of human pancreatic cells obtained from patients with insulinomas and from a newborn with nesidioblastosis. All cultures released insulin upon the addition of dibutyryl-cAMP and calcium, demonstrating their intact viability. Insulin secretion from nontumorous pancreatic cells surrounding an insulinoma was dose-dependently stimulated by glucose. In contrast, insulin release by B cells from a patient with nesidioblastosis and from 2 insulinomas was not stimulated by the addition of glucose. Native somatostatin (SRIF) and the synthetic analog SMS 201-995 inhibited insulin secretion from all cultures. The inhibitory effects of SRIF and SMS in the culture from the nesidioblastosis tissue, could be reversed by the addition of 11.2 mmol glucose/l, but not in one of the insulinoma cultures. This demonstrates that some sensitivity to glucose is present in B cells from the nesidioblastosis tissue, despite the unresponsiveness to glucose alone. Insulin release by insulinoma cells was blocked by somatostatin, while it was inhibited to some extent only in the cultures of nontumor B cells and of cells from the nesidioblastosis tissue. In conclusion, it was shown that insulin release by the cultured B cells obtained from several pathological conditions differed with regard to the autonomy of hormone release (glucose sensitivity) and the sensitivity to somatostatin and its analog.

Adenoma, Islet Cell↗
PubMed1987

Human medullary thyroid carcinoma in tissue culture; secretion of calcitonin and carcinoembryonic antigen.

Monolayer cultures of medullary thyroid carcinoma (MTC) cells were prepared from 5 patients with familial and 4 with sporadic MTC. Basal calcitonin (CT) release decreased rapidly during 17 days in culture. Addition of extra calcium (2 mmol/l) or dibutyryl cyclic AMP (dBcAMP, 3 mmol/l) increased CT release in all investigated cultures (p less than 0.01). No significant differences were observed between cell suspensions prepared from familial and those from sporadic MTC. Carcinoembryonic antigen (CEA) was found in 3 out of 5 MTC cell suspensions from patients with familial tumors and in 2 out of 2 sporadic tumors. Only two cultures secreted measurable amounts of CEA, which decreased with culture time but at a much slower rate than that of CT release. CEA release was not affected by the addition of calcium and dBcAMP. This study shows an absent relation between basal and stimulated CT and CEA release by cultured MTC cells.

Bucladesine↗
PubMed1987

Neuron-specific enolase as a guide to the treatment of small cell lung cancer.

A retrospective evaluation of serial measurements of neuron-specific enolase (NSE) has been performed in 58 patients with small cell lung cancer (SCLC). All 58 patients received first-line chemotherapy and 11 patients received also second-line treatment after relapse. Samples were obtained every 3-4 weeks during treatment before each cycle of chemotherapy and every 6 or 12 weeks during follow-up. NSE values were depicted on semi-logarithmic paper. Fifty-one times a major response (complete or partial remission) was observed and 49 times the NSE level reached a plateau between 3.5-10 ng/ml. The NSE level did not discriminate between a complete or a partial remission. Seven times stable disease was obtained and the NSE level declined but remained above the normal plateau of 3.5-10 ng/ml. On 50 occasions progressive disease was found. In 3 cases progressive disease was due to a histologically-proven non-small cell lung cancer and NSE levels did not change. In only 5 out of the remaining 47 occasions NSE levels were normal at the time of relapse but rose later in 4. On 42 occasions of progressive SCLC an exponential rise of NSE was found, often within the range of 3.5-20 ng/ml. None of 6 patients, who are still incomplete remission for 1-5 years, showed a consistent rise of NSE. Serial measurements of serum NSE, can predict the occurrence of a major response, stable disease and progressive disease outside the brain with a very high accuracy and seem to be at least a useful addition to standard investigational methods to guide the treatment of SCLC.

Adult↗
PubMed1987

The effects of bromocriptine, thyrotropin-releasing hormone, and gonadotropin-releasing hormone on hormone secretion by gonadotropin-secreting pituitary adenomas in vivo and in vitro.

The characteristics and dynamics of hormone secretion in vivo and in vitro were investigated in six patients with gonadotropin-secreting pituitary adenomas. All six tumors secreted and contained FSH and different combinations of LH, beta-LH, and alpha-subunit. In addition, immunohistochemical examination of the pituitary tumor tissue showed staining with both LH and FSH in three and either LH or FSH in the other three tumors. TRH and GnRH stimulated hormone secretion in vivo and in vitro, and they also increased the hormone content of the cultured tumor cells. Bromocriptine significantly inhibited hormone release and reduced the hormone content of the tumor cells. In vivo, 2.5 mg bromocriptine significantly suppressed plasma hormone levels; the inhibiting effect on alpha-subunit concentrations was in general more marked than that on LH and FSH. We conclude that hormone release by gonadotropin-secreting pituitary adenomas can be stimulated by TRH and GnRH and inhibited by bromocriptine. Most of these tumors synthesize FSH, but there is a wide variation in the production of LH, beta-LH, and alpha-subunits. The sensitivity of hormone release to bromocriptine suggests that chronic therapy with this drug might have a beneficial effect on pituitary tumor size.

Adenoma↗
PubMed1987

The effect of the somatostatin analog SMS 201-995 on normal growth hormone secretion in the rat. A comparison with the effect of bromocriptine on normal prolactin secretion.

The somatostatin analog SMS 201-995 was recently shown to be effective in suppressing GH secretion and in causing tumour shrinkage in patients with GH-secreting pituitary tumours. In this respect, the action of SMS 201-995 seems similar to that of the dopamine-agonist bromocriptine in patients with PRL-secreting pituitary tumours. In the present study we compared the respective effects of SMS 201-995 and bromocriptine on normal rat GH and PRL release in vivo and in vitro. Both in vitro and in vivo, repeated administration of SMS for up till 6 days suppressed circulating GH concentrations, and the ability of the pituitary glands to release GH in vitro. A dose-dependent diminution occurred of the total pituitary GH content in rats treated in vivo with SMS 201-995 for 4-6 days. During short-term in vitro incubation for only 4 h, the total amount of GH measured in the medium + gland was also diminished. Chronic administration with SMS 201-995 (2 micrograms/kg twice daily for 15 days), however, resulted in a complete desensitization of its inhibitory effect on GH synthesis and release. In similar experiments it was shown that the dopamine agonist bromocriptine affects normal PRL secretion in a different manner. Both in vitro (10 nmol/l) and in vivo administration for 6 days (0.2 mg/kg twice daily) greatly inhibited circulating PRL levels and the ability of the pituitary glands to release PRL in vitro. This is, however, in all instances accompanied by an accumulation of PRL within the pituitary gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Doubling time of neuron-specific enolase and survival in small cell lung cancer patients. Results of a preliminary analysis.

During a retrospective analysis of the value of neuron specific enolase (NSE) in patients with small cell lung cancer (SCLC) it became apparent that at progressive disease (PD) NSE rose exponentially with a doubling time (NSE-Td) varying from 10 - 94 days. In this study the influence of the NSE-Td on the survival of 29 SCLC-patients has been investigated. A significant correlation between survival from the start of rise of NSE at PD and NSE-Td was observed. By extrapolating the exponential rise of NSE to the start of treatment a theoretical logarithmic value of NSE, called Yr, could be calculated. When the patients were grouped according to the Yr value greater than -1, between -1 and -4 and less than or equal to -4 a highly significant correlation between the survival from the start of treatment and NSE-Td was found in all 3 groups. These preliminary data suggest that by means of NSE-Td and Yr value the survival of an SCLC-patient from the time of rise of NSE and from the start of treatment may be predicted within certain limits.

Carcinoma, Small Cell↗
PubMed1986

Differences in the interaction between dopamine and estradiol on prolactin release by cultured normal and tumorous human pituitary cells.

We studied the interaction between dopamine and estradiol on PRL release by cultured normal and tumorous PRL-secreting cells prepared from human pituitaries. If pituitary glands were obtained within 3 h after sudden death of previously normal individuals, the viability of isolated pituitary cells prepared by dispersion with dispase was more than 75%. After 4 days of culture, dopamine (500 nM) inhibited PRL release by cells prepared from four normal pituitaries by 24 +/- 3% (+/- SEM). Pretreatment of the cells with 100 nM estradiol did not alter dopamine-mediated inhibition of PRL release. Estradiol alone increased basal PRL release and cell PRL content. Cultured PRL-secreting pituitary tumor cells, obtained by transsphenoidal operation from four patients, were similarly sensitive to dopamine. Estradiol stimulated tumor cell PRL release and content, but significantly diminished the inhibitory effect of dopamine. The estrogen receptor blocker tamoxifen did not alter PRL release, but it did reverse the estradiol-induced insensitivity of the prolactinoma cells to the dopamine agonist bromocriptine. In conclusion, these in vitro results indicate that estrogens do not antagonize the effect of dopamine on normal human PRL-secreting pituitary cells. In human pituitary tumor cells, however, estradiol decreased the sensitivity of PRL release to dopamine (agonists), and the estrogen action can be acutely reversed by tamoxifen.

Aged↗
PubMed1986

Secretion of adrenocorticotropin, beta-endorphin and calcitonin by cultured medullary thyroid carcinoma cells. Effects of synthetic corticotropin-releasing factor and lysine vasopressin.

The present study was performed to investigate the potential of human medullary thyroid carcinoma (MTC) cells to secrete ACTH, beta-LPH/beta-EP. In addition, these studies might shed further light on the possible synthesis of a common precursor molecule for calcitonin (CT), ACTH and beta-LPH/beta-EP. MTC tissue was obtained from 10 patients (6 familial, 4 sporadic) without clinical and biochemical signs of Cushing's syndrome. Single cell suspensions were cultured for 1 to 2 weeks. Mean basal release of beta-LPH/beta-EP was 0.76 +/- 0.29 (SE) ng/10(6) cells/4 h (n = 10). Dibutyryl cyclic AMP (3 mM) stimulated beta-EP release significantly in 3 out of 7 cultures, while Ca2+ (2 mM) had no effect at all. The effects of the physiological regulators of pituitary ACTH and beta-LPH/beta-EP secretion, synthetic corticotropin-releasing factor (CRF-41) and vasopressin (LVP) were also studied in these MTC cell cultures. LVP (100 nM) had no effect on beta-EP release from MTC cells of all 8 cultures investigated. CRF-41 (10 nM) stimulated beta-EP release from 5 cultures and was without effect on 4. Maximal stimulation was noticed with 10 nM, while the effect of 100 nM CRF-41 was lower or absent. Stimulation was most outspoken in 3 cultures of familial MTC, whereas in 2 cultures of sporadic MTC CRF-41 stimulated beta-EP release marginally only after a 24 h incubation. LVP and/or CRF-41 stimulated CT release significantly in 3 cultures from sporadic MTC, while in these cultures the effect of CRF-41 on beta-EP release was either very small or absent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1985

The mechanism of action of cyproheptadine on prolactin release by cultured anterior pituitary cells.

The role of a direct effect of serotonin (5-HT) on PRL secretion at the pituitary level is uncertain. The present study investigated the mechanism of action of the serotonin receptor-blocking agent cyproheptadine on PRL release by normal cultured rat anterior pituitary cells. Cyproheptadine (10 nM-10 microM) and its metabolite desmethylcyproheptadine (a compound which has lost its affinity for serotonin receptors) directly inhibited PRL release, while serotonin, investigated over a wide concentration range, did not reverse this inhibition. The cyproheptadine-mediated inhibition of PRL-release could be completely prevented by 50 microM verapamil. Cyproheptadine strongly inhibited TRH-induced PRL release in the absence, but not in the presence of verapamil. Our studies suggest that cyproheptadine inhibits PRL release at the pituitary level by a blockade of calcium influx at the cell membrane, without affecting the movement of Ca2+ between intracellular compartments.

Animals↗
PubMed1985

Studies on the effects of catecholestrogens on prolactin secretion by cultured normal rat anterior pituitary cells.

The catecholestrogens 2-hydroxyesterone (2-OHE1) and 2-hydroxyestradiol (2-OHE2) are shown to directly inhibit PRL release by cultured normal rat anterior pituitary cells if they have been cultured in charcoal-treated estrogen-stripped fetal calf serum. Both catecholestrogens affect PRL release in a dose-dependent bimodal way. 2-OHE1 (1 microM) maximally inhibits PRL release by 38%, but 10 microM of the substance has no effect. In contrast, 0.1 microM 2-OHE2 maximally inhibits PRL release by 37%, while the effect of 1 microM of the compound was significantly less (-26%). The effect of the catecholestrogens on PRL release by cultured pituitary cells was significant after 2 h and was still effective after 48 h. The mechanism of action of 2-OHE1 and 2-OHE2 probably does not involve dopamine receptors, as 50 nM haloperidol did not alter the PRL release inhibitory effect of these substances. Moreover, 2-OHE1 and 2-OHE2 did not affect dopamine-mediated inhibition of PRL release. The total amount of PRL (medium plus cells) present in cultures of normal pituitary cells exposed to 2-OHE1 or 2-OHE2 was identical to that in control cells. TRH (100 nM)-stimulated PRL release from cells exposed to catecholestrogens was significantly higher than that from control cells. Addition of the calcium entry-blocking agent verapamil prevented the inhibitory effect of dopamine on PRL release, but did not prevent the effects of 2-OHE1 and 2-OHE2. Preincubation of cultured normal rat pituitary cells for 30 min with 50 nM estradiol completely prevented the inhibitory effects of 2-OHE1 and 2-OHE2 on PRL release. In conclusion, the acute inhibitory effects of the catecholestrogens 2-OHE1 and 2-OHE2 on PRL release by cultured normal rat pituitary cells do not involve dopamine receptors or calcium transport over the cell membrane. These effects are only demonstrable after culture of the cells in charcoal-treated fetal calf serum and can be completely prevented by short term preincubation with estradiol. Our observations support the suggestion that the action of estradiol on lactotropic cells may be modulated by its metabolites, which have opposite effects on PRL release.

Animals↗
PubMed1985

The somatostatin analog SMS 201-995 induces long-acting inhibition of growth hormone secretion without rebound hypersecretion in acromegalic patients.

The acute effect of the somatostatin analog SMS 201-995 (SMS) was investigated in eight acromegalic patients. This substance is an octapeptide [DPhe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-(ol)] that inhibits GH release in experimental animals and man. After a control day, 50 micrograms SMS were injected sc, and plasma GH and insulin and blood glucose levels were measured at multiple intervals for 24 h. GH significantly (P less than 0.001) decreased in seven of eight acromegalic patients from 30 +/- 5 (+/- SE) to an average of 10.7 +/- 4 micrograms/l from 1-10 h after drug administration. No rebound effect occurred. Postprandial blood glucose levels were significantly (P less than 0.01) higher between 2 and 4 h after SMS treatment compared with control day values, and there was a substantial reduction in insulin secretion, as estimated by the area under the curve (P less than 0.01), during the first 3 h after SMS administration. Circulating GH was not altered by SMS or the dopamine agonist mesulergine in one patient, but the combination of both substances (50 micrograms SMS, sc, and 0.5 mg mesulergine, orally) reduced GH to below 50% of basal. In vitro studies showed that 1 PM, 0.1 nM, and 10 nM SMS or natural somatostatin exerted a similar inhibitory effect (12-39% reduction; P less than 0.01 for all three strengths) on GH release by cultured human pituitary tumor cells. In conclusion, the somatostatin derivative SMS exerts a potent and prolonged inhibitory action on GH secretion and a shorter lasting suppression of insulin in acromegalic patients. Therefore, it may represent a useful tool in the chronic management of this condition.

Acromegaly↗
PubMed1985

Effect of long-term corticosteroid administration on rat pituitary growth hormone and prolactin.

In vitro corticosteroids stimulate GH synthesis by pituitary cells, while in vivo they suppress stimulated plasma GH levels. In this study we investigated in rats the effect of hydrocortisone administration for 2-4 weeks on pituitary GH content. Hydrocortisone added to the drinking water (100 mg/l) resulted in a marked stimulation of pituitary GH content after 3 and 4 weeks of treatment. No significant stimulation, however, was observed on basal GH release by the pituitary gland incubated in vitro. Further, we found that both Prl content and release were inhibited by hydrocortisone administration.

Animals↗
PubMed1985

Comparison of RIA kits with polyclonal antiserum and IRMA kits with monoclonal antibodies for the determination of plasma prolactin and somatotropin in patients with pituitary adenoma.

Size heterogeneity of prolactin and somatotropin has been demonstrated in human plasma. In patients with pituitary adenomas the ratio of some hormone fragments has been reported to be changed. Monoclonal antibodies that are used now in some commercial IRMA kits can theoretically differ from polyclonal antisera in the recognition of hormone variants or fragments. In this study, we found a perfect correlation between plasma levels of prolactin or somatotropin of patients with pituitary hypersecretion as measured by commercial RIA kits with polyclonal antiserum and IRMA kits with monoclonal antibodies. A negative bias of 30% for the somatotropin IRMA was found. We observed no discrepancies for plasma samples of patients with pituitary adenomas. Thus, the investigated IRMA kits with monoclonal antibodies seem to detect "tumour" prolactin and somatotropin equally as well as conventional RIA kits.

Adenoma↗