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J C Reubi

Publications and source records attributed to J C Reubi.

At least 181 records · Page 10Linked to original sources
PubMed1990

Somatostatin receptor imaging with 123I-Tyr3-Octreotide.

Somatostatin receptors have been shown to be present at all main sites of its action, such as the anterior pituitary gland, the exocrine and endocrine pancreas, the mucosa of the gastrointestinal tract and the central nervous system (1, 2). Somatostatin receptors can be measured by two different approaches (3). First by direct biochemical techniques, i.e. binding studies on tissue homogenates in vitro, which allow precise characterization of the affinities and kinetics of these receptors. Secondly, receptors can also be visualized in tissue sections with autoradiography. This last method has the advantage of identifying histologically the tissues containing these receptors. High numbers of high affinity somatostatin receptors have been found on most growth hormone secreting pituitary tumors, as well as on many endocrine pancreatic tumors and carcinoids (4, 5). These receptors probably form the pathophysiological basis for the successful control of hormonal hypersecretion by most of these tumors during treatment with octreotide (Sandostatin). Several other human tumor types have also been recognized to contain large numbers of high affinity somatostatin receptors. All 27 meningiomas investigated contained these receptors, while well-differentiated glia-derived brain tumors like most oligo-dendrogliomas and (low-grade) astrocytomas, but not glioblastomas contain somatostatin receptors (6-9). Somatostatin receptors have also been found on 20-40% of human breast cancers (10).

Autoradiography↗
PubMed1989

Prognostic value of receptors for insulin-like growth factor 1, somatostatin, and epidermal growth factor in human breast cancer.

The prognostic significance, as well as the relationship with known prognostic factors in breast cancer, of insulin-like growth factor 1 receptor (IGF-1-R), epidermal growth factor receptor (EGF-R), and somatostatin receptor (SS-R) was evaluated. IGF-1-R was positively correlated with estrogen receptor and age, but not significantly with progesterone receptor, lymph node status, and tumor size. EGF-R was negatively correlated to estrogen receptor and progesterone receptor, whereas no association was found with age, lymph node status, and tumor size. The levels of the tumor contents of IGF-1-R and EGF-R were not significantly related to tumor recurrence in 214 patients (test for trend, P = 0.20 and P = 0.08, respectively). However, patients with tumors containing intermediate levels of EGF-R (0.5 to 2.0 fmol/mg of membrane protein) experienced a longer disease-free survival than did patients with tumors possessing lower or higher levels of EGF-R. This effect was most pronounced in the subgroup of patients with positive axillary lymph nodes: 66% disease-free after 5 yr compared with 38% and 46% for the groups with lower and higher EGF-R levels, respectively. The relapse-free survival for patients with tumors containing SS-R (15%) was significantly longer than for patients with SS-R-negative tumors (82% versus 46% disease free after 5 yr, P = 0.04). Assessment by multivariate analysis showed that lymph node status, tumor size, and differentiation grade were independent prognostic factors for relapse. In the Cox model, estrogen receptor and progesterone receptor were both negatively correlated with tumor recurrence, whereas overall EGF-R and IGF-1-R did not show such a relation.

Adult↗
PubMed1989

Differential effects of somatostatin on adenylate cyclase as functional correlate for different brain somatostatin receptor subpopulations.

In homogenates of rat hippocampus and striatum, but not substantia nigra, somatostatin (SRIF) inhibits forskolin-activated adenylate cyclase in nanomolar concentrations. However, SRIF can also stimulate adenylate cyclase in micromolar concentrations in homogenates of rat hippocampus and substantia nigra. The SRIF octapeptide SMS 201-995 solely inhibits the forskolin-activated adenylate cyclase in the 3 preparations. These results suggest that the SRIF-specific stimulation of adenylate cyclase may be a functional correlate for the brain-specific SRIF receptor subpopulation, whereas the SRIF and SMS 201-995 inhibition of stimulated adenylate cyclase correlate with the SRIF receptor subpopulation present in brain and non-neuronal tissues.

Adenylyl Cyclase Inhibitors↗
PubMed1989

The relationship between somatostatin, epidermal growth factor, and steroid hormone receptors in breast cancer.

The somatostatin (SS) and the epidermal growth factor (EGF) receptor content have been established in 36 primary breast cancers by receptor autoradiography on adjacent tissue sections. Iodine 125 (125I)-EGF was used as radioligand for EGF receptor visualization whereas an iodinated SS-28 analogue or an octapeptide SS analogue were used to measure SS receptors. Six of 36 tumors contained SS receptors, whereas ten of the 36 tumors were shown to contain EGF receptors. None of the tumor samples containing SS receptors were simultaneously EGF receptor positive. In contrast, all SS receptor-positive tumors simultaneously contained steroid receptors. The positive correlation between SS receptors and steroid receptors as well as the negative correlation between SS receptors and EGF receptors therefore suggest that the small percentage of SS receptor-positive breast tumors are a group of differentiated breast tumors with a good prognosis. In these cases, combined hormonetherapy including SS analogs may be of potential interest.

Adult↗
PubMed1989

Correlative study on neuro-endocrine differentiation and presence of somatostatin receptors in breast carcinomas.

To correlate the expression of neuro-endocrine (NE) markers with the presence of somatostatin receptors (SSR) in human breast cancer, a series of 100 cases was stained with the Grimelius silver procedure, by immunocytochemistry with specific NE markers (i.e., chromogranin A and B and synaptophysin) and by autoradiography for SSR. Nine cases were positive for at least one NE marker, while 4 cases were positive for all of them. SSR were detected in 17 cases, either with low (10 cases) or with high receptor density (7 cases). A highly significant correlation was established between the expression of NE markers and high SSR density. Our findings are additional evidence of the existence of a group of breast cancers showing morphological and cytochemical similarity with neuro-endocrine tumors present in other organs. The identification of this type of breast cancer is of biological and potential therapeutic interest.

Adult↗
PubMed1989

Localisation of endocrine-related tumours with radioiodinated analogue of somatostatin.

Various endocrine-related tumours contain large numbers of high-affinity somatostatin receptors. 123I-labelled tyr-3-octreotide (tyr-3-SMS 201-995, a synthetic derivative of somatostatin) was used to localise such tumours in vivo with a gamma-camera. Positive scans were obtained for two meningiomas, two gastrinomas, and one carcinoid; negative scans were obtained for one insulinoma (in which unlabelled octreotide had no effect on insulin levels), one phaeochromocytoma, one adrenal carcinoma (octreotide had no effect on cortisol levels), and three medullary thyroid carcinomas (octreotide had no effect on calcitonin levels). Thus radioiodinated tyr-3-octreotide can label somatostatin receptors in endocrine-related tumours in vivo and can therefore be used for tumour localisation.

Adult↗
PubMed1989

Effects of gonadotropin-releasing hormone and its agonists on prolactin secretion from normal and tumorous pituitary cells.

Previous studies on the effect of gonadotropin-releasing hormone (LHRH) agonist on prolactin (PRL) secretion from normal and tumorous pituitary cells have not been conclusive as to the mechanism of action of these agonists. In this study the short-term administration of a LHRH agonist did not affect circulating PRL levels, but depleted the PRL content of the pituitary gland by 24, 49 and 73% after 2, 3 and 4 days, respectively, in normal female rats and by 75% after 4 days in normal male rats. This effect of the agonist could not be attributed to changes in the sex steroid environment: although plasma 17 beta-estradiol concentrations were significantly suppressed in female rats, circulating testosterone levels had not changed yet in the male rats. Interestingly, the pituitary luteinizing hormone (LH) content was depleted already from day 2 of LHRH agonist administration onwards, while the follicle-stimulating hormone (FSH) content of the pituitary glands had not changed even after 4 days. Culture studies with pituitary cells from normal adult male and female rats for 4-7 days did not reveal a direct effect of synthetic LHRH or an agonist on PRL release. Chronic systemic administration of a LHRH agonist greatly inhibited the growth of the transplantable PRL-secreting rat pituitary tumor 7315a in female rats, while circulating PRL levels were also suppressed. However, no direct effect of the LHRH agonist was observed on PRL release from a tumor cell clone, derived from the 7315a tumor, and no LHRH-binding sites were detectable on the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The growth hormone responses to octreotide in acromegaly correlate with adenoma somatostatin receptor status.

We studied the correlation between the presence of somatostatin (SRIH) receptors in GH secreting tumors and the in vivo GH responsiveness to the SRIH analog octreotide in 11 acromegalic patients. To test in vivo octreotide (SMS 201-995) responsiveness, the patients were given a single dose (100 micrograms, sc) and their plasma GH levels were measured for several hours. Somatostatin receptor content was measured by receptor autoradiography on frozen tumor tissue sections using either a somatostatin-28 analog or a SRIH octapeptide analog (Tyr3-octreotide) as iodinated radioligands. In eight acromegalic patients, who had complete and long lasting GH inhibition after octreotide administration, SRIH receptors with high affinity for octreotide were distributed homogeneously in the tumor tissue. Two patients had moderate, short duration, and incomplete inhibition of GH secretion after octreotide administration, and their tumors had very low capacity and/or affinity SRIH receptors. A further patient who had a moderate response to octreotide had SRIH receptors that were nonhomogeneously distributed throughout the tumor. These data suggest that the therapeutic efficacy of octreotide may be related to tumor SRIH receptor levels; the best in vivo responses to octreotide occurred in patients whose tumors contained a high density of homogeneously distributed receptors which had a high affinity for octreotide.

Acromegaly↗
PubMed1989

Coincidence of EGF receptors and somatostatin receptors in meningiomas but inverse, differentiation-dependent relationship in glial tumors.

Somatostatin (SS) receptors as well as EGF receptors have been shown to be present in various brain tumors such as meningiomas or glia-derived tumors. Using receptor autoradiography for both receptors, their localization on adjacent tumor sections was investigated and a correlation was attempted. In glia-derived tumors, there was an inverse relationship for the incidence of the two receptors in individual tumors: in a majority of cases (five of eight) of well-differentiated astrocytomas (I-II), SS receptors were present, but in none of the cases (zero of eight) EGF receptors were detected. In undifferentiated glioblastomas, the reverse situation was observed, no SS receptors were found (0 of 14) but EGF receptors were present in a majority of tumors (8 of 14). In astrocytomas III both types of receptors were normally seen. These data suggest that in glia-derived tumors, SS receptors are markers for the well-differentiated cases as opposed to EGF receptors. In meningiomas, SS receptors are found in all (27 of 27) tumors and EGF receptors in a large percentage (23 of 27) of the same tumors. However, in some cases a coincidence of both receptors on the same cell can be excluded. Furthermore, no effect of the SS analog SMS 201-995 on basal or EGF-stimulated growth of meningiomas in culture could be detected. Nevertheless, the coexistence of the two receptor types in meningiomas may be suggestive for a potential functional interaction between EGF and SS.

Autoradiography↗
PubMed1988

Absence of somatostatin receptors in human exocrine pancreatic adenocarcinomas.

Somatostatin receptor frequency was evaluated in 12 human exocrine pancreatic carcinomas taken after surgery. The tumors were analyzed by receptor autoradiography on tissue sections and by in vitro binding techniques on tumor homogenates. None of the tested human pancreatic carcinomas was shown to possess specific somatostatin receptors. In comparison, five single tumors taken from rats transplanted with the rat pancreatic adenocarcinoma CA 20948 were found to contain specific high-affinity somatostatin receptors. Also, human endocrine pancreatic tumors, i.e., two insulinomas, did contain somatostatin receptors under identical experimental conditions. These data confirm previous results with other tumors, documenting the absence of somatostatin receptors in highly malignant human carcinomas. They also may represent an explantation at the molecular level for the lack of therapeutic effect of somatostatin analogues such as SMS 201-995 seen in patients with advanced exocrine pancreatic carcinomas.

Adenocarcinoma↗
PubMed1988

Somatostatin receptors in normal and tumoral tissue.

Somatostatin receptors have been visualized with autoradiography and characterised biochemically in various somatostatin target tissues, such as brain, pituitary, pancreas and gastrointestinal tract, where they are likely to mediate the somatostatin actions. With the same methods, somatostatin receptors have been detected also in tumors originating from somatostatin target tissues: high receptor incidence is found in GH-producing pituitary adenomas as well as in some hormone-producing gastrointestinal tumors. These tumors are often highly responsive to somatostatin analogs in vivo. Among brain tumors, meningiomas usually contain a high density of receptors, suggesting a novel function for somatostatin in the human meninges. Among other human tumors tested, prostate, ovarian and endometrial carcinomas were free of receptors whereas 3 out of 39 mammary tumors contained somatostatin receptors.

Adenoma↗
PubMed1988

Development of resistance to a long-acting somatostatin analogue during treatment of two patients with metastatic endocrine pancreatic tumours.

UNLABELLED: Two patients with metastatic endocrine pancreatic tumours initially responded well to therapy with the long-acting somatostatin analogue SMS 201-995. In the first patient with an insulinoma both the number of hypoglycemic attacks and the increased insulin levels decreased initially, but returned to pretreatment intensity and concentrations within 9 days after the start of therapy with 200-300 micrograms SMS 201-995 daily. After a short interruption, no effect was observed of re-institution of therapy at a dose of 400 micrograms SMS 201-995 daily. In the other patient with a metastatic vipoma both diarrhea, hypokalemia and plasma VIP levels reacted initially well to SMS 201-995 treatment with 300 micrograms per day, but resistance to therapy developed after 2 weeks. An increase in the dose of the analogue to maximally 600 micrograms/day was followed by a transient improvement, but finally both the volume of diarrhea and the levels of vasoactive intestinal polypeptide were higher than those before the start of therapy. CONCLUSIONS: Development of resistance to SMS 201-995 both with regard to the clinical effect and to the inhibitory effect on tumour hormone secretion can be expected in some patients with metastatic endocrine pancreatic tumours. On the basis of our clinical observations down-regulation of somatostatin receptors is suggested to be one of the mechanisms of this development.

Adenoma, Islet Cell↗
PubMed1987

Distribution and biochemical characterization of somatostatin receptors in tumors of the human central nervous system.

Fifty-two brain tumors, consisting of 17 astrocytomas, 4 oligodendrogliomas, 20 glioblastomas, 3 neurinomas, 2 ependymomas, 1 neurofibroma, 1 ganglioneuroblastoma, 1 medulloblastoma, 1 plexus papilloma, 1 teratoma, and 1 germinoma, were tested for their content of specific somatostatin receptors using autoradiographic techniques or in vitro binding assays with membrane homogenates. Somatostatin receptors were found in most of the differentiated glia-derived tumors such as astrocytomas and oligodendrogliomas whereas the poorly differentiated glioblastomas were usually free of receptors. Tumors originating from neuroblasts, i.e., ganglioneuroblastoma and medulloblastoma, contained a high density of somatostatin receptors, whereas neurinomas and neurofibromas as well as the ependymomas, one teratoma, and one plexus papilloma were lacking such receptors. In one germinoma, low amounts of somatostatin receptors were observed over the lymphocytic elements. Receptor-positive tumors had saturable and high affinity receptors with pharmacological specificity for somatostatin and somatostatin analogues resembling that of normal human central nervous system tissue. In most instances, they could be labeled with two different iodinated radioligands, a somatostatin octapeptide derivative (204-090) or a somatostatin-28 analogue. This is the first time that somatostatin receptors have been shown to exist not only on neuronal structures of the central nervous system but also on glial elements. The precise function of such somatostatin receptors on glial cells, which may be different from neurotransmission, remains to be determined.

Adolescent↗