In vivo tumour imaging employing regional delivery of novel gallium radiolabelled polymer composites.

Background: Understanding the regional vascular delivery of particles to tumour sites is a prerequisite for developing new diagnostic and therapeutic composites for treatment of oncology patients. We describe a novel imageable Ga-radiolabelled polymer composite that is biocompatible in an animal tumour model and can be used for preclinical imaging investigations of the transit of different sized particles through arterial networks of normal and tumour-bearing organs.

Results: Radiolabelling of polymer microspheres with Ga was achieved using a simple mix and wash method, with tannic acid as an immobilising agent.

Neutralizing the pathological effects of extracellular histones with small polyanions.

Extracellular histones in neutrophil extracellular traps (NETs) or in chromatin from injured tissues are highly pathological, particularly when liberated by DNases. We report the development of small polyanions (SPAs) (~0.9-1.

Intestinal Sensing by Gut Microbiota: Targeting Gut Peptides.

There are more than 2 billion overweight and obese individuals worldwide, surpassing for the first time, the number of people affected by undernutrition. Obesity and its comorbidities inflict a heavy burden on the global economies and have become a serious threat to individuals' wellbeing with no immediate cure available. The causes of obesity are manifold, involving several factors including physiological, metabolic, neural, psychosocial, economic, genetics and the environment, among others.

Tc-radiolabeled composites enabling in vivo imaging of arterial dispersal and retention of microspheres in the vascular network of rabbit lungs, liver, and liver tumors.

Purpose: Selective internal radiation therapy (SIRT) is an effective treatment option for liver tumors, using Y-90-loaded polymer microspheres that are delivered via catheterization of the hepatic artery. Since Y-90 is a beta emitter and not conveniently imaged by standard clinical instrumentation, dosimetry is currently evaluated in each patient using a surrogate particle, Technetium-labeled macroaggregated albumin (Tc-MAA). We report a new composite consisting of Tc-labeled nanoparticles attached to the same polymer microspheres as used for SIRT, which can be imaged with standard SPECT.

Gut Microbiota: From Microorganisms to Metabolic Organ Influencing Obesity.

Objective: This review summarizes the current understanding of the relationship between gut microbiota and the host as it pertains to the regulation of energy balance and obesity.

Methods: The paper begins with a brief description of the gut microbiota environment, distribution, and its unique symbiotic relationship with the host. The way that enviromental factors influence microbiota composition and subsequent impact on the host are then described.

The uptake of soluble and nanoparticulate imaging isotope in model liver tumours after intra-venous and intra-arterial administration.

Delivery of chemotherapeutic drugs to tumours by reformulation as nanoparticles has often been proposed as a means of facilitating increased selective uptake, exploiting the increased permeability of the tumour vasculature. However realisation of this improvement in drug delivery in cancer patients has met with limited success. We have compared tumour uptake of soluble Tc99m-pertechnetate and a colloid of nanoparticles with a Tc99m core, using both intra-venous and intra-arterial routes of administration in a rabbit liver VX2 tumour model.

The accumulation of circulating histones on heparan sulphate in the capillary glycocalyx of the lungs.

Recent findings on the role of circulating histone proteins in mediating acute lung injury prompted us to investigate whether there is a specific mechanism for accumulation of histones in the lungs. Binding sites for polycations are already known in the vasculature of the lungs, and we postulated that these could also be involved in histone accumulation, since histones have a high content of positively charged amino acids. Using a histone-coated colloid of a radiolabelled nanocomposite to track histone biodistribution with imaging techniques, it was found that histones bind avidly in the lungs of rabbits after intravenous injection.

Cationised radiolabelled nanoparticles for perfusion imaging of the lungs.

Diagnostic imaging of the blood perfusion of the lungs is currently performed using particles of macro-aggregated albumin, which are mechanically arrested at limiting diameters of the capillary bed. While the proportion of blood flow obstructed is typically very low and temporary, it would seem more desirable to image lung perfusion in patients using a non-obstructive method, and using materials that avoid biological hazards. We have characterised the in vitro and in vivo properties of a colloid of a cationised radiolabelled nanocomposite.

Quantification of tissue inhibitor of metalloproteinases 2 in plasma from healthy donors and cancer patients.

Tissue inhibitor of metalloproteinases (TIMP)-2 is a highly conserved molecule, which binds both active and latent matrix metalloproteinase (MMP)-2. TIMP-2 is also involved in the activation of MMP-2 on the cell surface. A quantitative enzyme-linked immunosorbent assay (ELISA) was established and optimized for measurement of TIMP-2 in plasma.

Regression of Novikoff rat hepatocellular carcinoma following locoregional administration of a novel formulation of clofazimine in lipiodol.

We report here that, clofazimine (CFZ) treatment (0.1-10 microM) led to inhibition of in vitro proliferation of hepatocellular carcinoma (HCC) cell lines Hep3-beta, HuH-7, HepG2, SKHEP-1, PLC/PRF-5 and Novikoff. A 24 h exposure of human HuH-7 cells to various concentrations of CFZ dissolved in lipiodol (CFZ-L 10-160 microM), followed by 4 days treatment with medium alone, also led to dose-dependant inhibition of post-treatment cell growth.

Serum tetranectin is an independent prognostic marker in colorectal cancer and weakly correlated with plasma suPAR, plasma PAI-1 and serum CEA.

Soluble tetranectin (TN) was measured preoperatively in serum from 567 patients with primary colorectal cancer and levels were tested for association with prognosis. The prognostic significance of TN was also compared to that of plasminogen-activator inhibitor-1 (PAI-1), urokinase plasminogen activator (uPAR) and carcinoembryonic antigen (CEA). Significantly shorter survival was found for patients with TN levels below a cut-off point of 7.

Search for the production of single sleptons through R-parity violation in pp; collisions at square root (s) =1.8 TeV.

We report the first search for supersymmetric particles via s-channel production and decay of smuons or muon sneutrinos at hadronic colliders. The data for the two-muon and two-jets final states were collected by the D0 experiment and correspond to an integrated luminosity of 94+/-5 pb(-1). Assuming that R parity is violated via the single coupling lambda'211, the number of candidate events is in agreement with expectation from the standard model.

Search for R-parity violating supersymmetry in two-muon and four-jet topologies.

We present results of a search for R-parity-violating decay of the neutralino chi;01, taken as the lightest supersymmetric particle, to a muon and two jets. The decay proceeds through a lepton-number violating coupling lambda(')(2jk) (j=1,2; k=1,2,3), with R-parity conservation in all other production and decay processes. In the absence of candidate events from 77.

Urokinase receptor surface expression regulates monocyte adhesion in acute myocardial infarction.

The urokinase receptor (urokinase plasminogen activator receptor; uPAR) regulates monocyte adhesion by direct binding to vitronectin and by forming complexes with integrins. Therefore, possible up-regulation of uPAR in acute myocardial infarction (AMI) may affect monocyte adhesion. In 20 patients with AMI, uPAR surface expression (measured by flow cytometry) was increased compared with that in patients with chronic stable angina (mean +/- SD fluorescence, 179 +/- 96 vs 80 +/- 53; P =.

Prognostic significance of soluble urokinase plasminogen activator receptor in serum and cytosol of tumor tissue from patients with primary breast cancer.

Purpose: The aim of the study was to evaluate the prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in preoperatively obtained sera samples (s-suPAR) from breast cancer patients.

Experimental Design: suPAR levels were determined by the use of a kinetic ELISA in sera from 274 breast cancer patients and in tumor cytosols (c-suPAR) from 188 of these patients. In addition, s-suPAR levels were analyzed in 174 female blood donors.

Search for the scalar top quark in pp collisions at square root[s] = 1.8 TeV.

We have performed a search for scalar top quark (stop) pair production in the inclusive electron-muon-missing transverse energy final state, using a sample of pp events corresponding to 108.3 pb(-1) of data collected with the D0 detector at Fermilab. The search is done in the framework of the minimal supersymmetric standard model assuming that the sneutrino is the lightest supersymmetric particle.

Search for leptoquark pairs decaying into nunu+jets in pp collisions at square root[s] = 1.8 TeV.

We present the results of a search for leptoquark (LQ) pairs in (85.2+/-3.7) pb(-1) of pp* collider data collected by the D0 experiment at the Fermilab Tevatron.

Direct search for charged higgs bosons in decays of top quarks.

We present a search for charged Higgs bosons in decays of pair-produced top quarks in pp collisions at sqrt[s] = 1.8 TeV recorded by the D0 detector at the Fermilab Tevatron collider. With no evidence for signal, we exclude most regions of the ( M(H+/-),tan(beta)) parameter space where the decay t--> H(+)b has a branching fraction >0.

Total levels of tissue inhibitor of metalloproteinases 1 in plasma yield high diagnostic sensitivity and specificity in patients with colon cancer.

Purpose: The purpose of this study was to measure total levels of tissue inhibitor of metalloproteinases (TIMP-1) by ELISA in plasma from blood donors, patients with inflammatory bowel disease (IBD), and patients with cancer and to correlate the results to patient diagnosis.

Experimental Design: Total TIMP-1 plasma levels were measured by ELISA in blood samples from two different blood donor populations from IBD patients, and preoperative samples from patients with primary colon cancer (CC), rectal cancer (RC), or breast cancer.

Results: There were no significant differences in plasma TIMP-1 levels between healthy donors and IBD or breast cancer patients, whereas patients with CC or RC had significantly elevated TIMP-1 levels.

High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI-2) is an independent marker for shorter progression-free survival in patients with early stage endometrial cancer.

Previous studies including various tumor types have shown different associations between tumor tissue levels of plasminogen activator inhibitor 2 (PAI-2) and patient survival. High tumor tissue concentrations of PAI-2 have been associated with good prognosis in patients with breast cancer, small cell lung cancer and ovarian cancer, but with poor histologic differentiation and poor prognosis in patients with colorectal cancer. On the other hand, high tumor tissue concentrations of urokinase plasminogen activator (uPA), uPA receptor (R) and PAI-1 have more consistently been associated with poor histologic differentiation and poor prognosis.

Ratio of isolated photon cross sections in pp macro collisions at square root of s = 630 and 1800 GeV.

The inclusive cross section for production of isolated photons has been measured in pp macro collisions at square root of s = 630 GeV with the D0 detector at the Fermilab Tevatron Collider. The photons span a transverse energy (E(T)) range from 7-49 GeV and have pseudorapidity absolute value of eta < 2.5.

Search for new physics using QUAERO: a general interface to D0 event data.

We describe QUAERO, a method that (i) enables the automatic optimization of searches for physics beyond the standard model, and (ii) provides a mechanism for making high energy collider data generally available. We apply QUAERO to searches for standard model WW, ZZ, and t t macro production, to searches for these objects produced through a new heavy resonance, and to the first direct search for W'-->WZ. Through this interface, we make three data sets collected by the D0 experiment at square root of [s] = 1.

Increased stromal expression of murine urokinase plasminogen activator in a human breast cancer xenograft model following treatment with the matrix metalloprotease inhibitor, batimastat.

The matrix metalloprotease (MMP) family of enzymes and the urokinase plasminogen activator (uPA) pathway have both been implicated in tumor invasion and metastasis and in poor prognosis of cancer. We have previously shown that treatment with batimastat, a synthetic MMP inhibitor, leads to significant retardation but not regression of tumor growth in a human breast cancer xenograft model. In addition, batimastat treatment did not inhibit local tumor invasion, nor did it encourage stromal encapsulation of the tumor, suggesting the additional involvement of non-MMP proteolytic mechanisms.

Soluble urokinase plasminogen activator receptor in preoperatively obtained plasma from patients with gynecological cancer or benign gynecological diseases.

Objective: The present study was planned to measure preoperative levels of soluble urokinase plasminogen activator receptor (suPAR) in plasma from patients with gynecological diseases, and to test for a relationship to clinical and biochemical patient characteristics.

Methods: Using a specific and sensitive kinetic ELISA, suPAR levels were determined in preoperative citrate plasma samples from 53 ovarian, 34 endometrial, and 30 cervical cancer patients, 17 patients with benign ovarian tumors, and 28 patients with benign endometrial diseases. In addition, suPAR was measured in citrate samples from 31 female blood donors.

Search for heavy particles decaying into electron-positron pairs in pp collisions.

We present results of searches for technirho (rho(T)), techniomega (omega(T)), and Z' particles, using the decay channels rho(T),omega(T),Z'-->e(+)e(-). The search is based on 124.8 pb(-1) of data collected by the D0 detector at the Fermilab Tevatron during 1992-1996.