The present invention provides nanoparticle compositions comprising, for example, a core comprising a fluorescent silane compound; and a silica shell on the core. Also provided are methods for the preparation of nanoparticle compositions including fluorescent nanoparticles, ligated-fluorescent nanoparticles, ligated-fluorescent nanoparticles having therapeutic agents, and ligated-fluorescent nanoparticles coupled or associated with an analyte. Also provided are methods: for the detection of the ligated-fluorescent nanoparticles; for associating the linked-fluorescent nanoparticles with a cellular component of interest and recording or monitoring the movement of the cellular component; for improving the therapeutic properties of the therapeutic agent by combining the therapeutic agent with linked-fluorescent nanoparticles and contacting or administering the combination to a cell or organism; for making and using the fluorescent nanoparticles in, for example, diagnostic agents for the detection of various analytes, and like applications.

Fluorescent silica-based nanoparticles

Neuroendocrine tumors (NETs) constitute a heterogeneous group of neoplasms that originate from endocrine glands such as the pituitary, the parathyroids, and the (neuroendocrine) adrenal, as well as endocrine islets within glandular tissue (thyroid or pancreatic) and cells dispersed between exocrine cells, such as endocrine cells of the digestive (gastroenteropancreatic) and respiratory tracts. Conventionally, NETs may present with a wide variety of functional or nonfunctional endocrine syndromes and may be familial and have other associated tumors. Assessment of specific or general tumor markers offers high sensitivity in establishing the diagnosis and can also have prognostic significance. Imaging modalities include endoscopic ultrasonography, computed tomography and magnetic resonance imaging, and particularly, scintigraphy with somatostatin analogs and metaiodobenzylguanidine. Successful treatment of disseminated NETs requires a multimodal approach; radical tumor surgery may be curative but is rarely possible. Well-differentiated and slow-growing gastroenteropancreatic tumors should be treated with somatostatin analogs or alpha-interferon, with chemotherapy being reserved for poorly differentiated and progressive tumors. Therapy with radionuclides may be used for tumors exhibiting uptake to a diagnostic scan, either after surgery to eradicate microscopic residual disease or later if conventional treatment or biotherapy fails. Maintenance of the quality of life should be a priority, particularly because patients with disseminated disease may experience prolonged survival.

/pdf/the-diagnosis-and-medical-management-of-advanced-5bw7heqxt0.pdf

The diagnosis and medical management of advanced neuroendocrine tumors.

In vivo somatosensory stimuli evoked the release of substance P from primary afferent neurons that terminate in the spinal cord and stimulated endocytosis of substance P receptors in rat spinal cord neurons. The distal dendrites that showed substance P receptor internalization underwent morphological reorganization, changing from a tubular structure to one characterized by swollen varicosities connected by thin segments. This internalization and dendritic structural reorganization provided a specific image of neurons activated by substance P. Thus receptor internalization can drive reversible structural changes in central nervous system neurons in vivo. Both of these processes may be involved in neuronal plasticity.

https://science.sciencemag.org/content/sci/268/5217/1629.full.pdf

Receptor endocytosis and dendrite reshaping in spinal neurons after somatosensory stimulation

Summary
Background The discovery of somatostatin (SST) and the synthesis of a variety of analogues constituted a major therapeutic advance in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours (GEP-NETs). They currently provide the most efficient treatment to achieve symptomatic relief and have recently been demonstrated to inhibit tumour growth.

Aim  To review 35 years of experience regarding the clinical application and efficacy of SST analogues.

Methods  The PubMed database (1972–2009) was searched using somatostatin as a search term with combinations of terms including ‘treatment’; ‘neuroendocrine’; ‘carcinoid’; ‘tumor’; ‘octreotide’; ‘lanreotide’ and ‘pasireotide’.

Results  In a review of 15 studies including 481 patients, the slow-release formulations Sandostatin LAR and Somatuline SR/Autogel achieved symptomatic relief in 74.2% (61.9–92.8%) and 67.5% (40.0–100%), biochemical response in 51.4% (31.5–100%) and 39.0% (17.9–58%), and tumour response in 69.8% (47.0–87.5%) and 64.4% (48.0–87.0%) respectively. Novel SST analogues like SOM230 (pasireotide) that exhibit pan SST receptor activity and analogues with high affinity to specific somatostatin receptor (sstr) subtypes may further advance the field, but efficacy studies are lacking.

Conclusion  As more precise understanding of NET cell biology evolves and molecular biological tools advance, more accurate identification of individual tumours sstr profile will probably facilitate a more precise delineation of SST analogue treatment.

Aliment Pharmacol Ther 31, 169–188

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2036.2009.04174.x

Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours.

An understanding of the events that occur during GH receptor (GHR) signaling has facilitated the development of a GHR antagonist (pegvisomant) for use in humans. This molecule has been designed to compete with native GH for the GHR and to prevent its proper or functional dimerization-a process that is critical for GH signal transduction and IGF-I synthesis and secretion. Clinical trials in patients with acromegaly show GHR blockade to be an exciting new mode of therapy for this condition, and pegvisomant may have a therapeutic role in diseases, such as diabetes and malignancy, in which abnormalities of the GH/IGF-I axis have been observed. This review charts the discovery and development of GHR antagonists and details the experience gained in patients with acromegaly.

/pdf/growth-hormone-receptor-antagonists-discovery-development-2yxz67a3oo.pdf

Growth Hormone Receptor Antagonists: Discovery, Development, and Use in Patients with Acromegaly

Specific receptors for somatostatin (SS), mediating the various actions of this peptide, have been described in SS target tissues in animal and man Using homogenate binding assays, as well as receptor autoradiography, the presence of SS receptors has been demonstrated in various regions of the brain (cortex, limbic system, basal ganglia), the anterior pituitary, the endocrine and exocrine pancreas, the gastrointestinal tract, and the adrenals There are species-, as well as age-, related variations Furthermore, there is evidence for different SS receptor subtypes Interestingly, a large variety of human tumors also contain SS receptors with similar characteristics as those found in normal tissue; in numerous tumors, the SS receptor density is even higher than in healthy tissue counterparts Most GH- and TSH-producing pituitary adenomas, but also a subgroup of endocrine inactive pituitary adenomas, have SS receptors; most carcinoids and islet cell carcinomas, as well as their metastases, also contain SS receptors Several differentiated (usually EGF receptor negative) glia tumors possess SS receptors, whereas undifferentiated (EGF receptor positive) glia tumors lack such receptors Furthermore, a subgroup of breast tumors, usually steroid receptor positive and neuroendocrine-differentiated, contain SS receptors Finally, small cell lung carcinomas, but not non-small cell carcinomas, often possess SS receptors These receptors are likely to be functional since in 11 acromegalics and 18 gastroenteropancreatic tumor patients, a positive correlation was observed between their SS receptor status and their hormone secretion sensitivity to Sandostatin

E. Krenning

Papers

Distribution of somatostatin receptors in normal and tumor tissue.