Biomedical subjects

V D Corleto

Publications and source records attributed to V D Corleto.

At least 19 recordsLinked to original sources

PubMed2006

Somatostatin receptor subtypes mediate contractility on human colonic smooth muscle cells.

This study demonstrates the expression of functional somatostatin receptor (sstr) subtypes in human circular and longitudinal colonic smooth muscle cells (SMC). Native somatostatin (SS) and sstr subtype-specific analogues were used to characterize the sstr subtypes present in both cell types by contraction/relaxation studies. Qualitative and quantitative mRNA analysis and immunohistochemistry of sstr subtypes were also carried out. sstr subtype 2 mRNA was expressed in circular SMC, and various levels of subtypes 1, 2 and 3 mRNA were expressed in longitudinal colonic SMC. Native SS and each subtype-specific analogue exerted a modest, but significant, contraction, although inhibition of carbachol-induced contraction (relaxation) was the main effect on SMC from both layers. CH-288, a sstr subtype 1-specific analogue, and octreotide, a sstr subtype 2-specific analogue, were the most effective relaxant analogues on longitudinal and circular SMC, respectively. sstr subtypes display a distinct expression pattern on human colonic SMC; on circular SMC, subtype 2 is the only sstr, whereas sstr subtypes 1, 2 and 3 are expressed on human SMC isolated from the longitudinal layer. The contractile effects of SS are mediated through sstr subtype 2 and sstr subtype 1 on circular and longitudinal human colonic SMC, respectively.

Cells, Cultured↗

PubMed2006

Vasoactive intestinal peptide receptor subtypes and signalling pathways involved in relaxation of human stomach.

Vasoactive intestinal peptide (VIP) relaxes smooth muscle by interacting with receptors coupled to cAMP- or cGMP-signalling pathways. Their relative contribution to human gastric relaxation is unknown. This study aimed at investigating, in terms of biological activity, receptor expression and related signalling pathways, the action of VIP separately on the human fundus and the antrum. VIP caused greater relaxation of smooth muscle cells (SMC) and strips of the antrum presenting on the former a higher efficacy and potency (ED(50): 0.53 +/- 0.17 nmol L(-1)) than on the fundus (ED(50): 3.4 +/- 1.4 nmol L(-1)). On both fundus and antrum strips, its effect was tetrodotoxin insentitive. Reverse transcriptase-polymerase chain reaction analysis showed the sole expression of VPAC2 and natriuretic peptide clearance receptors, with VPAC2 being more abundant in the antrum. Functional regional differences in receptor-related signalling pathways were found. Activation of the cAMP-pathway by forskolin or its inhibition by adenylate cyclase (2'5'-dideoxyadenosine) or kinase (Rp-cAMPs) inhibitors had more pronounced effects on antrum SMC. Activation of the cGMP-pathway by sodium nitroprusside or its inhibition by guanylate cyclase (LY83583) or kinase (KT5823) inhibitors had more effects on fundus SMC, on which a higher expression of endothelial nitric oxide synthase was found. In conclusion, regional differences in VIP action on human stomach are related to distinct myogenic properties of SMC of the antrum and the fundus.

Adult↗

PubMed2004

Utility of combined use of plasma levels of chromogranin A and pancreatic polypeptide in the diagnosis of gastrointestinal and pancreatic endocrine tumors.

BACKGROUND: Chromogranin A (CgA) is considered the most accurate marker in the diagnosis of gastro-entero-pancreatic (GEP) endocrine tumors. Pancreatic polypeptide (PP) has also been proposed to play this role, but then not used due to its low sensitivity. The aim of the present study was to determine whether the assessment of PP would improve the diagnostic reliability of CgA in patients with GEP tumors. PATIENTS AND METHODS: Both markers were assessed in 68 patients [28 functioning (F), 40 non functioning (NF)]. Twenty-seven patients disease-free (DF) after surgery, and 24 with non-endocrine tumors (non-ETs) were used as control groups. RESULTS: CgA sensitivity was: 96% in F, 75% in NF, 74% in pancreatic, and 91% in gastrointestinal (GI) tumors. Specificity was 89% vs DF, and 63% vs non-ETs. PP sensitivity was: 54% in F, 57% in NF, 63% in pancreatic, and 53% in GI tumors. Specificity was 81% vs DF, and 67% vs non-ETs. By combining the two markers a significant gain in sensitivity vs CgA alone was obtained: overall in GEP tumors (96% vs 84%, p = 0.04), in NF (95% vs 75%, p = 0.02), and in pancreatic (94% vs 74%, p = 0.04). More specifically, a 25% gain of sensitivity was obtained in the subgroup of NF pancreatic tumors (93% vs 68%, p = 0.04). CONCLUSION: The combined assessment of PP and CgA leads to a significant increase in sensitivity in the diagnosis of GEP tumors, particularly in pancreatic NF.

Adult↗

PubMed2004

Somatostatin receptor subtypes: basic pharmacology and tissue distribution.

The heptahelical receptor superfamily constitutes the largest single family of transmembrane-signalling molecules that regulate a wide range of physiological processes. The five somatostatin receptors represent a distinct subgroup of this seven transmembrane receptor superfamily. They range in size from 356 to 391 amino acids with 39-57% protein identity between the subtypes with 100 residues strictly conserved among the somatostatin receptor sequences. A high grade of mRNA homology exists in somatostatin receptor subtypes cloned from different species. Following somatostatin receptor binding and functional activity studies, two alternative models of ligand-binding interaction have been hypothesised. One relies on the presence of a binding pocket within the receptor structure constituted by specific amino acids residues, the other denies the presence of such binding structures and suggests that it is the interaction of agonists with specific extracellular and/or transmembrane domains that determine stable receptor structure conformation. Somatostatin receptors, as, indeed, all G-protein-coupled receptors are able to regulate their responsiveness to agonist exposure. This agonist-specific regulation includes three main events, namely, desensitisation, receptor internalisation and receptor degradation. The cell expression of somatostatin receptor subtypes, at the mRNA level, has been characterised in rodent and in human organs with multiple subtype expression in brain and peripheral tissues.

Animals↗

PubMed2004

Unlabelled somatostatin analogues in treatment of digestive endocrine tumours.

Somatostatin analogues are considered first-line therapy in patients with digestive endocrine tumours. Indeed, several studies have investigated their efficacy in the control of specific symptoms and in the decrease of tumour markers. However, randomised controlled trials are needed in order to better define their role in non functioning tumours and their effect on tumour growth, which have seldom been assessed. Several new drugs have been developed over the last few years such as, for example, new long-acting formulations, universal analogues binding to all five somatostatin receptors subtypes, and cytotoxic analogues, all of which offer a promising therapeutic tool in the near future, even if further studies are needed to determine their efficacy and safety in man.

Digestive System Neoplasms↗

PubMed2004

Optimisation of isolation of richly pure and homogeneous primary human colonic smooth muscle cells.

BACKGROUND: Inherent properties of gastrointestinal smooth muscle can be assessed using isolated cell suspensions. Currently available isolation techniques, based on short 2-h enzymatic digestion, however, present the disadvantage of low cellular yield with brief viability. These features are an important limiting factor especially in studies in humans in which tissue may not be available daily and mixing of samples is not recommended. AIMS: To optimise the isolation procedure of cells from human colon to obtain a richly pure primary smooth muscle cell preparation. METHODS: Slices of circular muscle layer, obtained from surgical specimens of human colon, were incubated overnight in Dulbecco's modified eagle's medium supplemented with antibiotics, foetal bovine serum, an ATP-regenerating system and collagenase. On the following day, digested muscle strips were suspended in HEPES buffer, and spontaneously dissociated smooth muscle cells were harvested and used either immediately or maintained in suspension for up to 72 h. Cell yield, purity, viability, contractile responses, associated intracellular calcium signals and RNA and protein extraction were evaluated and compared to cell suspensions obtained with the current short digestion protocol. RESULTS AND CONCLUSION: The overnight isolation protocol offers the advantage of obtaining a pure, homogeneous, long-life viable cell suspension that maintains a fully differentiated smooth muscle phenotype unchanged for at least 72 h and that allows multiple functional/biochemical studies and efficient RNA extraction from a single human specimen.

Cell Separation↗

PubMed2003

Co-existence of hyperparathyroidism, hypergastrinaemia and multiple gastric carcinoids is not always due to incomplete expression of the MEN-1 syndrome.

Until recently, the association of primary hyperparathyroidism and gastric carcinoid, with or without hypergastrinaemia, had been considered an incomplete form of multiple endocrine neoplasia type 1. This is because it seemed unlikely that the rare joint appearance of these diseases could occur only by chance. It is now possible to evaluate the pathogenetic involvement of the multiple endocrine neoplasia type 1 gene in many, apparently sporadic, clinical conditions. This is a case report of a female mimicking multiple endocrine neoplasia type 1 due to the presence of hyperparathyroidism, gastric carcinoid, and hypergastrinaemia. However, involvement of the MEN-1 gene (exons 2-10) was not detected, whereas hypergastrinaemia was attributed to a chronic atrophic gastritis.

Aged↗

PubMed2003

Staging of digestive endocrine tumours using helical computed tomography and somatostatin receptor scintigraphy.

BACKGROUND: In patients with digestive endocrine tumours, complete pre-operative staging is essential in planning proper management and evaluating treatment efficacy. To date, somatostatin receptor scintigraphy (SRS) is considered the 'gold standard' imaging procedure, and very few data are available concerning the use of helical computed tomography (hCT). This study aimed to determine the diagnostic accuracy and the ability to modify the surgical management of hCT, alone or combined with SRS. PATIENTS AND METHODS: Sixty patients were staged before surgery by hCT, SRS and tumour markers, and included in group 1 if suitable for radical surgery, otherwise in group 2. All patients underwent laparotomy followed by subsequent re-staging. RESULTS: SRS sensitivity was 77%, 48% and 67% for primary, lymph-node and liver lesions, respectively. hCT sensitivity was 94%, 69% and 94% for primary, lymph-node and liver lesions, respectively (P = 0.02 versus SRS, for liver lesions). During pre-operative evaluation, hCT correctly staged 92% and SRS 75% of patients (P = 0.02). hCT provided additional information in 17% of patients. CONCLUSIONS: Since hCT has been shown to be extremely accurate, providing essential information for the planning of surgical treatment compared with that of SRS, both techniques should be used in the pre-operative work-up of digestive endocrine tumours.

Adolescent↗

PubMed2002

Progression of gastric enterochromaffin-like cells growth in Zollinger-Ellison syndrome and atrophic body gastritis patients.

BACKGROUND: Enterochromaffin-like cell hyperplasia of the gastric body mucosa occurs in hypergastrinaemic conditions such as atrophic body gastritis and Zollinger-Ellison syndrome. However, the time course of change or factors involved are not known. AIMS: To compare the rate of change of enterochromaffin-like cell proliferation in patients with atrophic body gastritis and Zollinger-Ellison syndrome. PATIENTS: From a consecutive series of atrophic body gastritis and Zollinger-Ellison syndrome patients, studied at the time of first diagnosis, 10 atrophic body gastritis (4 with pernicious anaemia) and 14 Zollinger-Ellison syndrome (4 with multiple endocrine neoplasia type 1) patients were followed-up for a median time of 48 months. METHODS: At entry and during follow-up patients underwent: plasma gastrin determination, endoscopic sampling of body mucosa for qualitative assessment of enterochromaffin-like cell hyperplasia pattern and degree of glandular atrophy, qualitative and morphometric analyses of body mucosa endocrine cells. RESULTS: At time of diagnosis, enterochromaffin-like cell lesions were more severe in atrophic body gastritis than in Zollinger-Ellison syndrome. During follow-up, no significant variations were observed in gastrin values, enterochromaffin-like cell patterns and grade of body mucosa atrophy in atrophic body gastritis. In contrast, gastrin levels were significantly increased [median 1200 (235-2625) vs 1947 (225-5200) pg/ml; p<0.001)] as was total volume density of enterochromaffin-like cells [median 1.60 (0.53-4.06) vs 3.18 (1.35-21.13)% of mucosal epithelial component; (p<0.005)] in Zollinger-Ellison syndrome. Micronodular hyperplasia of enterochromaffin-like cells, present in only one patient at diagnosis, was observed in 8 Zollinger-Ellison syndrome patients at follow-up. CONCLUSIONS: These data suggest that the progression of enterochromaffin-like cell growth in human gastric mucosa requires an increase of and/or a prolonged exposure to severe hypergastrinaemia.

Adult↗

PubMed2002

Molecular insights into gastrointestinal neuroendocrine tumours: importance and recent advances.

A subset of gastrointestinal neuroendocrine tumours (carcinoids and pancreatic endocrine tumours) show aggressive growth. Early identification of this subset is essential for management; however, clinical, laboratory and histologic features frequently fail to achieve this. Currently, there is an increased understanding of the molecular pathogenesis/changes in neuroendocrine tumours and this may identify important prognostic factors and possibly, new treatments. Recent findings and progress in this area are briefly reviewed in this article.

Gastrinoma↗

PubMed2001

Digestive neuroendocrine tumours: diagnosis and treatment in Italy. A survey by the Oncology Study Section of the Italian Society of Gastroenterology (SIGE).

BACKGROUND: New insights in the diagnosis and treatment of digestive neuroendocrine tumours have prompted a renewed interest in these rare and complex diseases. AIM: To establish how many new cases of digestive neuroendocrine tumours were diagnosed, and how they were treated, at gastroenterological centres across Italy during a two-year period (1997-1998). METHODS: The 12 centres taking part filled in a data collection form reporting type of tumour, methods of diagnosis and therapeutic strategies adopted in each case. Data were collected and analysed by the authors of the present report. RESULTS: Data refer to 98 patients, 22 with functioning and 76 with non-functioning digestive neuroendocrine tumours [50 carcinoids, 48 pancreatic endocrine tumour syndromes]. Primary tumours were localised in 96% (38% with metastases) of non-functioning and 81% (50% with metastases) of functioning tumours. These were surgically removed in >80% of patients in both groups. Somatostatin analogue treatment, with or without interferon, was administered in 35% of patients, while chemotherapy was used in 9% and 23% of functioning and non-functioning tumours, respectively. The imaging study always included a computed tomography scan (20% helical computed tomography). Magnetic resonance and somatostatin receptor scintigraphy were also performed, the former in 41% and 21% of the two (functioning and non-functioning tumour) groups, the latter in 45% and 30%. CONCLUSIONS: The number of functioning digestive neuroendocrine tumours reported was lower than expected. Surgery plays a major role in the treatment of these tumours in all centres. Overall, in only a small number of patients was a multidisciplinary approach applied.

Adolescent↗

PubMed2001

Does the widespread use of proton pump inhibitors mask, complicate and/or delay the diagnosis of Zollinger-Ellison syndrome?

BACKGROUND: Proton pump inhibitors are potent acid suppressants which, at normal doses, can result in hypergastrinaemia in patients with idiopathic oesophageal reflux disease and in the control of symptoms in most patients with gastrinomas. Therefore, their use could delay or mask the diagnosis of gastrinoma. AIM: To investigate whether the widespread use of proton pump inhibitors masks or complicates the diagnosis of gastrinoma. SUBJECTS AND METHODS: Data from two centres with different referral criteria for suspected gastrinomas were analysed (Gastroenterology Unit, Rome, Italy and National Institutes of Health, Bethesda, MD, USA). The number of referrals and the number of new patients with gastrinoma diagnosed in the years prior to the widespread use of proton pump inhibitors (1986-1992) were compared with the numbers since proton pump inhibitors became widely available (1993-1998). RESULTS: The decrease in referral rate (P=0.0009) and the decrease in the annual rate of gastrinoma diagnosis (P=0.0020) at both centres correlated with the increased use of proton pump inhibitors. At the Italian centre, there was a 62% decrease in annual referrals (P < 0.0001) in the post-proton pump inhibitor period, relative to the pre-proton pump inhibitor period, whereas there was an increase in the rate of referral of other gastrointestinal endocrine tumours. The number of new cases of gastrinoma diagnosed decreased by 40%. At the US centre, the referral rate decreased by 28% (P=0.024) in the post-proton pump inhibitor period. There was also a 43% decrease in the number of new cases diagnosed annually in the post-proton pump inhibitor period (P=0.0012). There was a 2.6-fold increase in the post-proton pump inhibitor period in the percentage of referrals with a false diagnosis of gastrinoma as the cause of hypergastrinaemia (P=0.0040). CONCLUSIONS: In both referral centres, less patients have been referred with a possible diagnosis of gastrinoma and fewer new patients with gastrinoma have been diagnosed since proton pump inhibitors became widely available. These data support the conclusion that, since proton pump inhibitors have been released, the diagnosis of gastrinoma has been masked and will probably be delayed, with the result that patients with gastrinoma will be diagnosed at more advanced stages in their disease course.

Anti-Ulcer Agents↗

PubMed2001

Inhibitory effect of somatostatin on neutral amino acid transport in isolated brain microvessels.

In the presence of somatostatin-14 or some of its receptorial agonists, the uptake of large neutral amino acids by isolated brain microvessels was found to be inhibited up to 50%, no other transport system being affected. Although the luminal and abluminal sides of brain endothelial cells are both capable of taking up large neutral amino acids, only uptake from the abluminal side appears to be inhibited by somatostatin. The involvement of a type-2 somatostatin receptor was suggested by assays with a series of receptor-specific somatostatin agonists, and was confirmed by the release of inhibition caused by a specific type-2 receptor antagonist. A type-2-specific mRNA was indeed shown to be present in both bovine brain microvessels ex vivo and primary cultures of endothelial cells from rat brain microvessels.

Amino Acids, Neutral↗

PubMed2001

p27: a potential main inhibitor of cell proliferation in digestive endocrine tumors but not a marker of benign behavior.

The immunohistochemical expression of the inhibitors of cyclin-dependent kinases p21 and p27 was investigated in 109 endocrine tumors of the pancreas and gastrointestinal tract and compared with that of Ki67 and p53. p21 was found to be scarcely expressed without significant differences between benign and malignant or between differentiated and undifferentiated tumors. This suggests no relationship between changes in p21 levels and clinical behavior in these endocrine tumors. p27 was found to be highly expressed in differentiated neoplasms and proved to be inversely related to Ki67 labeling (P =.02), which was usually low. These data indicate that p27 may have an important inhibiting role on the low proliferation rate of the tumors. Moreover, the protein may have a role in the resistance of differentiated endocrine tumors to chemotherapeutic agents. p27 high-expressor neoplasms were frequent in either benign (70.6%) or malignant (81.4%) differentiated tumors, thus not allowing the use of this protein for the differential diagnosis of malignant neoplasms as suggested for endocrine tumors of parathyroid and pituitary. Poorly differentiated endocrine carcinomas, which differred from the differentiated tumors for their very high Ki67 levels and frequent p53 expression, showed low or absent p21 and p27 in most cases. Classical midgut carcinoids were characterized by a sharp discrepancy between malignant behavior and very bland proliferative pattern, with Ki67 and p27 expressions similar to that of benign tumors.

Adenoma, Islet Cell↗

PubMed2001

Atrophic body gastritis patients with enterochromaffin-like cell dysplasia are at increased risk for the development of type I gastric carcinoid.

BACKGROUND/AIMS: In the presence of atrophic body gastritis, gastric carcinoid develops from gastric-body mucosa enterochromaffin-like cells. Few data exist on the prevalence of enterochromaffin-like dysplastic lesions in atrophic body gastritis patients and their presumed risk of evolution to carcinoid has never been assessed prospectively in humans. The aim of the present study was to investigate the prevalence and incidence of dysplastic and neoplastic enterochromaffin-like cell lesions in a consecutive series of patients with atrophic body gastritis. METHODS: A total of 130 atrophic body gastritis patients at diagnosis and 96 atrophic body gastritis patients at follow-up (median 30 months) underwent gastroscopy with multiple biopsies and fasting gastrinaemia evaluation. In patients with enterochromaffin-like cell dysplasia, a more detailed bioptic sampling at follow-up was performed. RESULTS: Of the 130 atrophic body gastritis patients, only one (0.7%) had a gastric carcinoid polyp, whereas enterochromaffin-like cell dysplasia was found in five patients (3.8%). At follow-up only one out of the 96 atrophic body gastritis patients (1%) was diagnosed as having a carcinoid polyp at 41 months. Enterochromaffin-like cell dysplasia was present in four additional patients (4.2%). Two atrophic body gastritis pernicious anaemia patients with enterochromaffin-like cell dysplasia developed a gastric carcinoid in the follow-up. Among nine atrophic body gastritis patients with enterochromaffin-like cell dysplasia, the incidence of carcinoid tumour was 22% compared to 1.1% of atrophic body gastritis patients without dysplasia (odds ratio: 26.00; 95% confidence interval: 2.089-323.52). During the follow-up, fasting gastrin levels increased significantly only in atrophic body gastritis patients with enterochromaffin-like cell dysplasia (mean 677.4 +/- 66.1 vs 1112.2 +/- 185.6; P = 0.0287). CONCLUSION: This study provides the first clinical evidence that, in hypergastrinaemic atrophic body gastritis patients, enterochromaffin-like cell dysplasia carries a markedly increased risk for development of type I gastric carcinoid. This suggests that a more detailed endoscopic/bioptic procedure in this subgroup of atrophic body gastritis patients is able to detect gastric carcinoid at an early stage.

Adult↗

PubMed2001

The antral mucosa as a new site for endocrine tumors in multiple endocrine neoplasia type 1 and Zollinger-Ellison syndromes.

Carcinoid tumors were identified in the antro-pyloric mucosa of four patients with multiple endocrine neoplasia type 1 (MEN-1)/Zollinger-Ellison syndrome, accounting for 8.7% of 46 patients with this condition examined by endoscopy and histology. In contrast, no tumors were found in the antral biopsies from 124 cases of sporadic Zollinger-Ellison syndrome (P < 0.001), indicating a prominent role for the MEN-1 gene defects in tumor development. Immunohistochemically the tumors did not express the hormones produced by antral endocrine cells (gastrin, somatostatin, serotonin). In contrast, two of them were diffusely immunoreactive for the isoform 2 of the vesicular monoamine transporter (VMAT-2), a marker specific for the gastric nonantral enterochromaffin-like (ECL) cells. In one of these patients a second antral VMAT-2-positive carcinoid was seen 21 months after the first diagnosis. The other two antral carcinoids were unreactive for VMAT-2. Multiple ECL cell tumors were found in the gastric body-fundus mucosa of the two patients with VMAT-2-positive, but not in those with VMAT-2-negative, antral carcinoids. In one case, the former tumors were diagnosed 22 months after the detection of the antral tumor. We conclude that the antral mucosa is an additional tissue that may harbor endocrine tumors in MEN-1 syndrome. These tumors did not express the phenotype of normal antral endocrine cells and, in at least two cases, were identified as ectopic ECL cell carcinoids.

Adult↗

PubMed2001

Oncogenes, growth factors, receptor expression and proliferation markers in digestive neuroendocrine tumours. A critical reappraisal.

BACKGROUND: The main characteristic of the digestive neuroendocrine tumours (dNETs) is the low proliferating activity, even in the presence of malignant, metastatic behavior. PATIENTS AND METHODS: Considering that dNETs are rare diseases, relatively numerous studies, often including a conspicuous number of patients, have recently investigated the molecular mechanisms of neuroendocrine tumour genesis. RESULTS: In contrast to non-endocrine tumours of the digestive system such as carcinoma of the pancreas, colon and stomach, dNETs do not show alterations in oncogenes (ras, Myc, fos jun, Src) or in common tumor suppressor genes [p53, retinoblastoma suspectibility gene (Rb)]. MEN-1 gene alterations will likely be important in a proportion of sporadic dNETs. The role of various growth factors, novel oncogenes and tumour suppressor genes have also been investigated. However, results from these studies are non-conclusive and to date the molecular pathogenesis of these tumours has not been clarified. Studies on somatostatin receptor expression and synthetic analogues, as growth inhibitors in dNETs, although promising, have not reproduced in vivo all the antiproliferative effects showed in in vitro models. CONCLUSION: Although various functional genes and molecular mechanisms have been investigated in dNETs, to date the molecular pathogenesis of these tumours remains to be elucidated.

Biomarkers, Tumor↗

PubMed2000

Long-term octreotide treatment of metastatic carcinoid tumor.

The optimal dosage of somatostatin analogs for the long-term control of carcinoid tumors has not yet been established. Receptor alterations induced during long term treatment with somatostatin analogs have lead to consecutive drug dosage increases in order to control carcinoid disease. In this report, we describe the rapid and effective control of tumor in a patient with metastatic carcinoid treated for nine years with a single daily dose of octreotide based on tumor marker levels. Tumoral somatostatin receptor (sst) subtype analysis by RT-PCR amplification showed the expression of sst2 subtype only. We suggest that a single daily dose of octreotide strictly related to tumor marker secretion, could have played a role in the effective long-term therapy by avoiding the phenomenon of somatostatin receptor desensitisation. Furthermore, the exclusive presence of sst2 subtype supports the high affinity of octreotide to tumoral cells.

Antineoplastic Agents, Hormonal↗