Nanoparticle-Encapsulated Epirubicin Efficacy in the Inhibition of Growth of Orthotopic Ovarian Patient-Derived Xenograft in Immunocompromised Mice.

Epirubicin hydrochloride (EPI) is an anticancer drug widely used in the treatment of many solid tumors, including ovarian cancer. Because of its anatomical location, ovarian cancer shows symptoms when it is already in an advanced stage and is thus more difficult to treat. Epirubicin hydrochloride kills cancer cells effectively, but its dose escalation is limited by its severe toxicity.

Neurotoxicity of poly(propylene imine) glycodendrimers.

Published results of studies on poly(propylene imine) (PPI) dendrimers indicate their potential use in the treatment of brain cancer or neurodegenerative diseases due to their ability to cross the blood-brain barrier. However, depending on dose, neurotoxicity may occur. Here, we discuss the impact of maltotriose modified PPI dendrimers on rat's nervous system.

Maltotriose-modified poly(propylene imine) Glycodendrimers as a potential novel platform in the treatment of chronic lymphocytic Leukemia. A proof-of-concept pilot study in the animal model of CLL.

Cancer nanotherapeutics have shown promise in resolving some of the limitations of conventional drug delivery systems such as nonspecific biodistribution and targeting, lack of water solubility, and low therapeutic indices, Among the various nanoparticles that are available, dendrimers, highly branched macromolecules with a specific size and shape, are one of the most promising ones. In this preliminary study, we tested the anti-tumor activity of maltotriose-modified fourth-generation poly(propylene imine) glycodendrimers (PPI-G4-M3) in vivo in the subcutaneous MEC-1 xenograft model of human chronic lymphocytic leukemia (CLL) in NOD scid gamma mice. Fludarabine was used for model validation and as a positive treatment control.

Anti-Tumour Activity of Glycodendrimer Nanoparticles in a Subcutaneous MEC-1 Xenograft Model of Human Chronic Lymphocytic Leukemia.

Background: Chronic Lymphocytic Leukaemia (CLL) is an indolent disorder, which mainly affects older adults. Since the advent of chemoimmunotherapy, great progress has been made in its treatment. However, some patients develop a more aggressive form of the disease and are included in the group of high-risk CLL patients with a dismal prognosis and a need for new therapies.

Role of probiotics in the prevention and treatment of meticillin-resistant Staphylococcus aureus infections.

Meticillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant micro-organism and is the principal nosocomial pathogen worldwide. Following initial in vitro experiments demonstrating that Lactobacillus acidophilus CL1285(®) and Lactobacillus casei LBC80R(®) commercial strains exhibit antibacterial activity against clinical MRSA isolates, we conducted a literature search to find any evidence of probiotic efficacy in decolonisation or treatment of S. aureus infection.

[Physiological functions of L-ornithine and L-aspartate in the body and the efficacy of administration of L-ornithine-L-aspartate in conditions of relative deficiency].

L-ornithine-L-aspartate (LOLA) is a stable salt of two natural nonessential L-amino acids: ornithine and aspartic acid. It is formulated and marketed in low and high doses. Low doses are used as a food supplement and high doses (above 5 g) as a medicinal product to lower blood ammonia concentration and to eliminate symptoms of hepatic encephalopathy associated with liver cirrhosis.

A super-agonist of growth hormone-releasing hormone causes rapid improvement of nutritional status in patients with chronic kidney disease.

Chronic kidney disease is frequently associated with protein-energy wasting related to chronic inflammation and a resistance to anabolic hormones such as insulin and growth hormone (GH). In this study, we determined whether a new GH-releasing hormone super-agonist (AKL-0707) improved the anabolism and nutritional status of nondialyzed patients with stage 4-5 chronic kidney disease randomized to twice daily injections of the super-agonist or placebo. After 28 days, this treatment significantly increased 24-h GH secretion by almost 400%, without altering the frequency or rhythmicity of secretory bursts or fractional pulsatile GH release, and doubled the serum insulin-like growth factor-1 level.

Screening for okadaic acid by immunoassay.

Increasing incidences of phytoplankton blooms with the potential danger of toxin release into the food chain have necessitated the search for new diagnostic methods that can detect toxins quickly and reliably. A competitive enzyme-linked immunosorbent assay (ELISA) was developed to quantitate okadaic acid in shellfish and phytoplankton extracts. To determine the specificity of the assay, a number of toxins, such as calyculin A, brevetoxin-1, and dinophysistoxins-1, -2, and -3 were analyzed.

Evaluation of a 99mTc-antimyosin kit for myocardial infarct imaging.

The Fab fragment of a mouse monoclonal antibody AM(3-48) that recognizes alpha and beta-heavy chains of human atrial and ventricular myosin and beta-heavy chain of human slow skeletal muscle myosin [CardioVisionTM] was labeled with 99mTc using stannous reductant in a simple, instant kit method. The infarcted heart uptake in dogs of 99mTc-AM(3-48)Fab' was compared with that of established radiopharmaceuticals routinely used for cardiac imaging in humans. The dog infarct was induced by bringing a catheter from the femoral artery to the coronary artery where an artificial blood clot was generated.

An anti-okadaic acid-anti-idiotypic antibody bearing an internal image of okadaic acid inhibits protein phosphatase PP1 and PP2A catalytic activity.

Okadaic acid (OA), produced by marine phytoplankton, is the parent compound of a family of marine toxins responsible for diarrheic shellfish poisoning (DSP). A monoclonal antibody to OA (6/50) (Ab1) has been raised and in turn used for immunization of syngeneic animals. Mice inoculated with the 6/50 idiotype produced both anti-idiotypic antibodies (Ab2) and OA binding antibodies (Ab3).

An idiotypic-anti-idiotypic competitive immunoassay for quantitation of okadaic acid.

A competitive indirect enzyme-linked immunosorbent assay for the measurement of okadaic acid, a marine toxin, was developed. The assay uses a murine monoclonal anti-idiotypic antibody bearing an internal image of okadiac acid epitope to capture an anti-okadaic acid monoclonal antibody in the presence of free okadaic acid. Bound anti-okadaic acid antibody is detected with peroxidase-conjugated anti-mouse immunoglobulin antiserum.

Immunohistochemical characterization of a new anti-carcinoembryonic antigen monoclonal antibody.

A novel anti-CEA monoclonal antibody C234 with no cross-reactivity to other members of CEA gene family was produced by immunization with heat-treated CEA. The immunoreactivity of C234 was tested on formalin fixed normal and neoplastic tissues by peroxidase/anti-peroxidase technique. None of normal tissues from healthy or diseased individuals, except for normal colonic mucosa were stained.

Infarcted heart uptake and biodistribution of radiolabelled anti-myosin monoclonal antibody in rat and dog myocardial infarct models.

A new mouse monoclonal antibody that recognizes alpha- and beta-heavy chains of human atrial and ventricular myosin and beta-heavy chain of human slow skeletal muscle myosin was obtained. The 125I- and 111In-labelled antibody, and its F(ab')2 and Fab fragments localize in isoproterenol induced infarcted rat heart, with the F(ab')2 fragment showing the highest uptake. Comparison with 99Tc-pyrophosphate uptake in infarcted dog heart, induced by selective obstruction of a coronary artery, suggest that the 111In-labelled F(ab')2 localizes specifically in infarcted myocardium only.

Experimental antitumor activity of new azathioprine analogues.

Two newly synthesized azathioprine (AZA) analogues, 6-(1,2-dimethyl-4-nitro-5-imidazolyl)thiopurine (Met-AZA) and 6-(2-methyl-5-nitro-4-imidazolyl)thiopurine (IZO-AZA), were investigated against KB human tumor cells. In 5 transplantable murine tumor models, including sc Sa180, sc Ca755, ip LL and ip leukemias; L1210 and P388 both drugs were found to be antitumor active in all the experiments carried out regardless of dosing regimen or the route of administration. Similar good activity was shown in the KB, ip Sa180, and Ca755 systems and partly against LL as compared to AZA.

Tumor-associated antigens as immunotherapy targets.

The potential of liposomes to act as immunoadjuvant carriers of tumor-associated antigens (TAA) has been investigated. The incorporation of B16 melanoma TAA within liposomes resulted in immunological recognition by non-tumor-bearing mice, and subsequent inhibition of tumor growth upon tumor challenge. The immunogenicity and protective activity were enhanced by the concomitant incorporation of a lipophilic immunoadjuvant, MDP-GDP, in the liposome preparation.

Clinical applications of carcinoembryonic antigen.

Although carcinoembryonic antigen (CEA) has been the subject of interest for many investigators for over 20 years, many questions still remain unanswered concerning the CEA molecule. These include the ultimate clinical potential of CEA as a tumor marker (specificity, sensitivity, distribution), the biological role of CEA, and the genetic control of CEA synthesis. Initially, much of the work with CEA concerned its physicochemical and immunochemical properties, as well as of cross-reacting molecules, and methods of serologic detection of CEA.

Liposomal incorporation and immunogenicity of carcinoembryonic antigen.

The ability of liposomal carriers to act as immuno-adjuvants for carcinoembryonic antigen (CEA) has been evaluated. Liposomal incorporation was consistent with association with the aqueous phase of the liposome, little if any of the protein being associated with the phospholipid bilayer. The incorporation of CEA within liposomal carriers resulted in immunological recognition in mice at doses (0.

Anti-thyroglobulin anti-idiotypic antibodies in sera of patients with Hashimoto's thyroiditis and Graves' disease.

The objective of this study was to find naturally occurring anti-idiotypic (anti-Id) antibodies to anti-human thyroglobulin (anti-hTg) idiotype in sera of patients with autoimmune thyroid disease. Sera from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) and sera from normal subjects were tested for the presence of anti-Id antibodies against mouse anti-hTg monoclonal antibodies (McAb) in indirect ELISA and in indirect solid-phase RIA. Microtitration plates were coated with six McAb, five of them directed against different epitopes on hTg molecule, and then incubated with patients' sera.

Evaluation of an enzyme-linked immunosorbent assay for the measurement of autoantibodies against eye muscle membrane antigens in Graves' ophthalmopathy.

We have tested for antibodies against human and pig eye muscle membrane antigens in the serum of patients with Graves' ophthalmopathy using an enzyme-linked immunosorbent assay (ELISA). Several different membrane preparations were used as source of putative antigen including a 100,000 X g pellet, a pellet depleted of the 100,000 X g (microsome) fraction, and solubilized membranes. With eye muscle membrane pellets there were no significant differences for either serum or immunoglobulins between patients with ophthalmopathy, those with autoimmune thyroid disorders without eye disease, and normal subjects for either human or pig membranes, although tests were positive determined from the upper limit of normal in a few patients with or without eye disease.

Use of monoclonal antibodies to investigate a possible role of thyroglobulin in the pathogenesis of Graves' ophthalmopathy.

One possible mechanism for Graves' ophthalmopathy is that the progressive orbital inflammation is initiated by formation of thyroglobulin (Tg)-anti-Tg immune complexes at sites of Tg binding to extraocular muscle membranes. In this study monoclonal antibodies (MCAB) against human Tg were used as probes (1) to identify Tg in eye muscle membranes prepared from normal subjects and (2) to measure binding of human Tg and Tg-anti-Tg immune complexes to eye muscle membranes. Reactivity of anti-Tg MCAB with Tg, thyroid, and eye muscle membranes was determined by binding of [125I]anti-Tg monoclonal antibody, an enzyme-linked immunosorbent assay (ELISA), and the indirect immunofluorescence technique.

Demonstration of a circulating autoantibody against a soluble eye-muscle antigen in Graves' ophthalmopathy.

Mouse monoclonal antibodies against antigens in human eye muscle, orbital connective tissue, and lacrimal tissue and guineapig harderian gland have been produced by means of the hybridisation technique. From 14 fusions, over 30 antibodies have been produced, of which 24 have been maintained and characterised for the present studies. All were IgG1.

Selective induction of T-cell subsets capable of accelerating and retarding Lewis lung carcinoma.

The influence of three T-cell subsets on tumor growth was studied. The first, induced by a thymic microenvironmental fraction, accelerated the appearance of Lewis lung carcinoma in Winn assay. The second subset, derived from the first by incubation with a thymic hormone preparation, had a marked retarding effect on tumor appearance.