Formation of Multicolor Nanogels Based on Cationic Polyfluorenes and Poly(methyl vinyl ether-alt-maleic monoethyl ester): Potential Use as pH-Responsive Fluorescent Drug Carriers.

In this study, we employed the copolymer poly(methyl vinyl ether-alt-maleic monoethyl ester) (PMVEMA-Es) and three fluorene-based cationic conjugated polyelectrolytes to develop fluorescent nanoparticles with emission in the blue, green and red spectral regions. The size, Zeta Potential, polydispersity, morphology, time-stability and fluorescent properties of these nanoparticles were characterized, as well as the nature of the interaction between both PMVEMA-Es and fluorescent polyelectrolytes. Because PMVEMA-Es contains a carboxylic acid group in its structure, the effects of pH and ionic strength on the nanoparticles were also evaluated, finding that the size is responsive to pH and ionic strength, largely swelling at physiological pH and returning to their initial size at acidic pHs.

p,p-Dihydroxydihydrostilbenophanes related to antimitotic combretastatins. Conformational analysis and its relationship to tubulin inhibition.

The structures of a new family of macrocyclic analogues of combretastatins B combining oxygenated substituents on the phenyl rings and indole rings are described. The effects of the stereochemistry, of the length of the spacer linking both aryl groups, and of the decoration of the macrocycles on the kinematics of the system have been studied by means of NMR studies at several temperatures and in different solvents combined with theoretical studies including Monte Carlo conformational searches and molecular dynamics simulations at different temperatures. The new indole macrocycles provide a more rigid view of this kind of macrocycles than that previously held.

New para-para stilbenophanes: synthesis by McMurry coupling, conformational analysis and inhibition of tubulin polymerisation.

The synthesis of a new family of methoxy-substituted [2.7]- and [2.8]paracyclophanes linked by 3-oxapentamethylene-1,5-dioxy and hexamethylene-1,6-dioxy bridges has been carried out by using the McMurry methodology.

The MEN1 gene and pituitary tumours.

Sporadic multiple endocrine neoplasia type 1 (MEN1) is defined as the occurrence of tumours in two of three main endocrine tissue types: parathyroid, pituitary and pancreaticoduodenal. A prolactinoma variant or Burin variant of MEN1 was found to occur in three large kindreds, with more prolactinomas and fewer gastrinomas than typical MEN1. MEN1 tumours differ from common tumours by showing features from the MEN1 gene (e.

Rare germline mutations in cyclin-dependent kinase inhibitor genes in multiple endocrine neoplasia type 1 and related states.

Context: Germline mutation in the MEN1 gene is the usual cause of multiple endocrine neoplasia type 1 (MEN1). However, the prevalence of identifiable germline MEN1 mutations in familial MEN1 cases is only 70%. Some cases may have a germline mutation in another gene such as the p27 cyclin-dependent kinase inhibitor (CDKI).

Parathyroid tumor development involves deregulation of homeobox genes.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome caused by mutations in the MEN1 tumor suppressor gene. Loss of the functional second copy of the MEN1 gene causes individuals to develop multiple endocrine tumors, primarily affecting the parathyroid, pituitary, and pancreas. While it is clear that the protein encoded by MEN1, menin, suppresses endocrine tumors, its biochemical functions and direct downstream targets remain unclear.

Synthesis and conformational analysis of macrocyclic dihydroxystilbenes linked between the para-para positions.

A new family of diphenylethanes has been synthesized as conformationally restricted analogues of antimitotic combretastatins. The two phenyl rings are linked between the para-phenolic positions through a 3-oxapentamethylene or hexamethylene chain. The key macrocyclization step was achieved in moderate yields by using an intramolecular McMurry pinacol coupling of linked aromatic dialdehydes, except for the nitro-substituted compounds.

The parathyroid/pituitary variant of multiple endocrine neoplasia type 1 usually has causes other than p27Kip1 mutations.

Context: One variant of multiple endocrine neoplasia type 1 (MEN1) is defined by sporadic tumors of both the parathyroids and pituitary. The prevalence of identified MEN1 mutations in this variant is lower than in familial MEN1 (7% vs. 90%), suggesting different causes.

Stilbenophane analogues of deoxycombretastatin A-4.

A new family of polyoxygenated stilbenophanes has been synthesized as conformationally restricted analogues of antimitotic combretastatins. By means of the McMurry olefination process, compounds derived from diethyleneglycol and 1,6-hexanediol were obtained, whereas Grubbs' catalyst failed in producing the ring-closing metathesis to this kind of macrocyclic products.

Increased expression of insulin-like growth factor I and/or its receptor in gastrinomas is associated with low curability, increased growth, and development of metastases.

Purpose: Growth factors, particularly insulin-like growth factor I (IGF-I) and IGF-I receptor (IGF-IR) in some nonendocrine and a few endocrine tumors, are thought important in recurrence, growth, and aggressiveness. Whether this is true of neuroendocrine tumors such as gastrinomas is unclear. The aim of this study was to address this question in gastrinomas.

Further naphthylcombretastatins. An investigation on the role of the naphthalene moiety.

By synthesis and biological studies of new naphthalene analogues of combretastatins, we have found that the naphthalene is a good surrogate for the isovanillin moiety (3-hydroxy-4-methoxyphenyl) of combretastatin A-4, always generating highly cytotoxic analogues when combined with the 3,4,5-trimethoxyphenyl or related systems. On the other hand, when the naphthalene replaces the 3,4,5-trimethoxyphenyl moiety, the cytotoxic activity is largely decreased. The most cytotoxic naphthalene analogues of combretastatins, which also produce inhibition of tubulin polymerization, exerted their antimitotic effects through microtubule network disruption and subsequent G(2)/M arrest of the cell cycle in human cancer cells.

Multiple endocrine neoplasia type 1 variant with frequent prolactinoma and rare gastrinoma.

No variant of multiple endocrine neoplasia type 1 (MEN1) has been reproducible among families. We examined two large kindreds with MEN1 variants, and we compared these to past reports. The two kindreds were followed up for 20-30 yr with MEN1 tumors in 30 members.

Molecular pathology of the MEN1 gene.

Multiple endocrine neoplasia type 1 (MEN1), among all syndromes, causes tumors in the highest number of tissue types. Most of the tumors are hormone producing (e.g.