Biomedical subjects

J C Reubi

Publications and source records attributed to J C Reubi.

239 records · Page 14Linked to original sources

PubMedDate not supplied

The intestinal immune system and its relation to disease.

The essential protective structure against the heavy enteric antigenic burden, the gut mucosa, prevents penetration of noxious agents, but allows a minimal exchange of large molecules and particles between the gut lumen and the 'milieu intérieur' of the body. M cells in the follicle-associated epithelium of the gut, ideal gateways for the presentation of enteric antigens to the cells of the gut-associated lymphoid tissue (GALT), are also weak links in the mucosal barrier, and may provide access for various microorganisms. The afferent limb of the GALT consists of distinct aggregates of lymphoid cells located in Peyer's patches, the vermiform appendix and the solitary lymphatic follicles, and of the mesenteric lymph nodes. The efferent limb subsumes the diffusely scattered mucosal leukocytes, mainly lymphocytes and plasma cells. Intraepithelial and mucosal T lymphocytes are instrumental in launching local immune responses, producing lymphokines, and in the specific lysis of virally infected cells. Antigenic stimulation of the GALT results in local secretion of antibodies, or in suppression of systemic immunologic responses to ingested antigens ('oral tolerance'). Poorly controlled mucosal immune responses result in organ-specific diseases. Extranodal lymphomas that mimic structures of the GALT may arise on a background of inflammatory or immunologic (autoimmune) disorders.

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Receptor imaging of human diseases using radiolabeled peptides.

The peptide somatostatin and its analog octreotide play an important role in neoplasia where their actions have been shown to be mediated by specific somatostatin receptors located in the tumor tissue. The identification of a high density of SS receptors in vitro in different types of human tumors has provided completely new and attractive possibilities for their diagnostic localization in vivo. This can be achieved by intravenous injection of 123I-[Tyr3]-octreotide or 111In-DTPA-D-Phe1-octreotide in patients suspected of having SS receptor-positive tumors and by subsequent localization of the tumors with gamma camera scintigraphy techniques. Hot spots representing radioligand binding on SS receptor-positive tumors are visualized with this method. This new SS receptor imaging method may help the clinicians for the localization of the primary tumor and its metastases, for the staging of certain tumors, to predict a successful SS therapy, and as a prognostic or differential diagnostic marker. It may also be of use in non-tumoral pathologies, to localize selected inflammatory processes and to monitor anti-inflammatory therapy. Somatostatin receptor imaging represents the first example of the clinical use of a small peptide as an efficient in vivo diagnostic tool and may be considered as a paradigm for further research on the role and the potential diagnostic use of other peptide receptors in pathological states.

Amino Acid Sequence↗

PubMedDate not supplied

Somatostatin receptors in the gastrointestinal tract in health and disease.

The multiple actions of somatostatin are mediated by specific membrane-bound receptors present in all somatostatin target tissues, such as brain, pituitary, pancreas, and gastrointestinal tract. Three different types of tissues in the human gastrointestinal tract express somatostatin receptors: (1) the gastrointestinal mucosa, (2) the peripheral nervous system, and (3) the gut-associated lymphoid tissue, where the receptors are preferentially located in germinal centers. In all these cases, somatostatin binding is of high affinity and specific for bioactive somatostatin analogs. Somatostatin receptors are also expressed in pathological states, particularly in neuroendocrine tumors of the gastrointestinal tract. Ninety percent of the carcinoids and a majority of islet-cell carcinomas, including their metastases, usually have a high density of somatostatin receptors. Only 10 percent of the colorectal carcinomas and none of the exocrine pancreatic carcinomas, however, contain somatostatin receptors. The somatostatin receptors in tumors are identified with in vitro binding methods or with in vivo imaging techniques; the latter allow the precise localization of the tumors and their metastases in the patients. Since somatostatin receptors in gastroenteropancreatic tumors are functional, their identification can be used to assess the therapeutic efficacy of octreotide to inhibit excessive hormone release in the patients.

Animals↗

PubMedDate not supplied

The presence of somatostatin receptors in malignant neuroendocrine tumor tissue predicts responsiveness to octreotide.

In 77 percent of patients suffering from a malignant carcinoid syndrome, administration of the somatostatin analog, octreotide (SMS 201-995, Sandostatin) induced clinical improvement coupled with a decrease in 24-hour urinary 5-hydroxyindole acetic acid (5-HIAA). This finding prompted an evaluation to determine the correlation between the presence of somatostatin receptors in tumor tissue and the response to octreotide in patients with advanced, metastatic, neuroendocrine tumors. In tissues of 31 tumors (20 carcinoid, eight islet-cell carcinoma, three medullary thyroid carcinomas), the presence of somatostatin receptors was analyzed by binding of the somatostatin analog 125I-Tyr3-SMS 201-995 and autoradiography. Receptors were detected in 16 of 20 samples of carcinoid tissues; all but one patient with receptor-positive tumors improved clinically after treatment with octreotide, and the urine 5-HIAA level was reduced a median of 63 percent (range, 39-94 percent) compared to values before treatment. Of the receptor-negative carcinoid patients, only one showed clinical improvement, which was minimal, and there was a negligible reduction in 5-HIAA after octreotide therapy. All eight patients with metastatic islet-cell carcinomas were positive for somatostatin receptors. Symptomatic improvement and a > 50 percent decrease in the level of at least one of the pathologically elevated marker hormones was seen in all eight. None of the three patients with medullary carcinoma of the thyroid had a decrease in calcitonin, and all three were initially somatostatin receptor-negative. We conclude that the presence of somatostatin receptors in malignant neuroendocrine tumor tissue appears to correlate with the response to octreotide therapy. Analysis of somatostatin receptors in malignant neuroendocrine carcinoma tissue should be included in future prospective clinical trials of this synthetic peptide.

Amino Acid Sequence↗

PubMedDate not supplied

Distribution of somatostatin receptors in normal and neoplastic human tissues: recent advances and potential relevance.

This short review describes the localization of somatostatin receptors with in vitro receptor autoradiography techniques in several non-classical, normal human somatostatin target tissues as well as in selected human tumors. In addition to brain, gut and neuroendocrine localizations, somatostatin receptors are expressed in most lymphatic tissues, including gut-associated lymphatic tissue, spleen and thymus; in the cortical and medullary area of the kidney; in the stroma of the prostate and in the epithelial cells of the thyroid. Among human tumors, the extremely high density of somatostatin receptors in medulloblastomas should be stressed as well as the favorable prognostic role of the presence of somatostatin receptors in neuroblastomas. Moreover, several types of mesenchymal tumors have somatostatin receptors as well. The receptor subtypes expressed by distinct tumors may vary: Whereas medulloblastomas and neuroblastomas predominantly express sst2, prostate cancers express sst1 rather than sst2. A further emerging somatostatin target is represented by the peritumoral veins, also known to express sst2 receptors. The multiple somatostatin targets in normal and pathological human tissues represents the basis for potential diagnostic and clinical applications of somatostatin analogs.

Humans↗