The novel cytotoxic polybisphosphonate osteodex decreases bone resorption by enhancing cell death of mature osteoclasts without affecting osteoclastogenesis of RANKL-stimulated mouse bone marrow macrophages.

It has previously been demonstrated that the polybisphosphonate osteodex (ODX) inhibits bone resorption in organ-cultured mouse calvarial bone. In this study, we further investigate the effects by ODX on osteoclast differentiation, formation, and function in several different bone organ and cell cultures. Zoledronic acid (ZOL) was used for comparison.

Cytotoxicity of poly-guanidine in medulloblastoma cell lines.

Medulloblastoma (MB) is the most common pediatric brain tumor. The therapy frequently causes serious side effects, and new selective therapies are needed. MB expresses hyper sialylation, a possible target for selective therapy.

A randomised, double-blind, dose-finding, phase II multicentre study of ODX in the treatment of patients with castration-resistant prostate cancer and skeletal metastases.

Aims: This study aimed to assess the efficacy and safety of ODX, a novel, cytotoxic, bone-targeting drug candidate, in castration-resistant prostate cancer bone metastatic disease.

Methods: Patients with progressive disease were randomised to ten cycles of ODX, intravenous infusion Q2W (3, 6, and 9 mg/kg, respectively). The primary objective was to assess the relative change from baseline in bone alkaline phosphatase (B-ALP) and serum-aminoterminal-propeptide of Type I procollagen (S-P1NP) at 12 weeks.

Poly-guanidine shows high cytotoxicity in glioma cell cultures and glioma stem cells.

Glioblastoma multiforme (GBM) is a malignant CNS tumor with a poor prognosis. GBM shows aberrant glycosylation with hypersialylation. This property is a potential target for therapy.

Object symmetry effects in Germanic: Evidence for the role of case.

This paper focuses on passive symmetry effects in Germanic. We describe two large-sample judgment experiments with native speakers of Norwegian and Swedish, two partially symmetric passive languages. The results fail to support predictions of Anagnostopoulou's (2003) seminal locality approach to passive symmetry in these languages.

Synthesis and Binding of a Novel PSMA-specific Conjugate.

Background/aim: Prostate-specific membrane antigen (PSMA) is emerging as a target for treatment of castration-resistant prostate cancer (CRPC) while its up-regulated in the majority of CRPC tumors. The most common approach is targeted radionuclide therapy.

Materials And Methods: The PSMA binding pharmacophore Glu-Urea-Lysine (GUL) and lysine were conjugated to oxidized dextran with reductive amination and subsequently labelled with fluorosceinisothiocyanate (FITC).

Fatigue performance of a high-strength, degradable calcium phosphate bone cement.

Calcium phosphate cements (CPCs) are clinically used as injectable materials to fill bone voids and to improve hardware fixation in fracture surgery. In vivo they are dynamically loaded; nonetheless little is known about their fatigue properties. The aim of this study was to, for the first time, investigate the fatigue performance of a high-strength, degradable (brushitic) CPC, and also evaluate the effect of cement porosity (by varying the liquid to powder ratio, L/P) and the environment (air at room temperature or in a phosphate buffered saline solution, PBS, at 37°C) on the fatigue life.

Bone-targeted Novel Cytotoxic Polybisphosphonate Conjugate in Castration-resistant Prostate Cancer: A Multicenter Phase 1 Study.

Background: Osteodex (ODX) is a cytotoxic bone-targeting polybisphosphonate, intended for treatment of bone metastasis from castration-resistant prostate cancer (CRPC). The primary objective of this study was to describe the tolerability and toxicity of such treatment by defining its maximum tolerated dose (MTD) and dose-limiting toxicity (DLT).

Patients And Methods: Twenty-eight patients with castration-resistant prostate cancer and confirmed bone metastasis were assigned to seven infusions of ODX every third week, divided in seven ascending dose cohorts.

Somatostatin Derivate (smsDX) Attenuates the TAM-Stimulated Proliferation, Migration and Invasion of Prostate Cancer via NF-κB Regulation.

Tumor development and progression are influenced by macrophages of the surrounding microenvironment. To investigate the influences of an inflammatory tumor microenvironment on the growth and metastasis of prostate cancer, the present study used a co-culture model of prostate cancer (PCa) cells with tumor-associated macrophage (TAM)-conditioned medium (MCM). MCM promoted PCa cell (LNCaP, DU145 and PC-3) growth, and a xenograft model in nude mice consistently demonstrated that MCM could promote tumor growth.

Solid-phase cloning for high-throughput assembly of single and multiple DNA parts.

We describe solid-phase cloning (SPC) for high-throughput assembly of expression plasmids. Our method allows PCR products to be put directly into a liquid handler for capture and purification using paramagnetic streptavidin beads and conversion into constructs by subsequent cloning reactions. We present a robust automated protocol for restriction enzyme based SPC and its performance for the cloning of >60 000 unique human gene fragments into expression vectors.

3D simulation of the image formation in soft x-ray microscopes.

In water-window soft x-ray microscopy the studied object is typically larger than the depth of focus and the sample illumination is often partially coherent. This blurs out-of-focus features and may introduce considerable fringing. Understanding the influence of these phenomena on the image formation is therefore important when interpreting experimental data.

A semi-automated magnetic capture probe based DNA extraction and real-time PCR method applied in the Swedish surveillance of Echinococcus multilocularis in red fox (Vulpes vulpes) faecal samples.

Background: Following the first finding of Echinococcus multilocularis in Sweden in 2011, 2985 red foxes (Vulpes vulpes) were analysed by the segmental sedimentation and counting technique. This is a labour intensive method and requires handling of the whole carcass of the fox, resulting in a costly analysis. In an effort to reduce the cost of labour and sample handling, an alternative method has been developed.

Proteomic analysis of soft tissue tumor implants treated with a novel polybisphosphonate.

Background: Osteodex is a novel bi-functional macromolecular polybisphosphonate developed for treatment of bone metastases in prostate and breast cancer. High efficacy of osteodex has been demonstrated both in vitro and in vivo. The present study investigates whether osteodex is also efficacious on soft tissue tumor lesions.

Damage investigation on tungsten and diamond diffractive optics at a hard x-ray free-electron laser.

Focusing hard x-ray free-electron laser radiation with extremely high fluence sets stringent demands on the x-ray optics. Any material placed in an intense x-ray beam is at risk of being damaged. Therefore, it is crucial to find the damage thresholds for focusing optics.

Ronchi test for characterization of nanofocusing optics at a hard x-ray free-electron laser.

We demonstrate the use of the classical Ronchi test to characterize aberrations in focusing optics at a hard x-ray free-electron laser. A grating is placed close to the focus and the interference between the different orders after the grating is observed in the far field. Any aberrations in the beam or the optics will distort the interference fringes.

Treatment of bone metastasis in prostate cancer: efficacy of a novel polybisphosphonate.

Aim: To investigate the in vivo efficacy of a novel polybisphosphonate (ODX) in the treatment of bone metastasis from prostate cancer.

Material And Methods: A rat prostatic carcinoma model was used. Forty-two rats (21 control, 21 treatment) had induction of bone lesions through injection of AT6.

Application of accelerator mass spectrometry to macromolecules: preclinical pharmacokinetic studies on a polybisphosphonate.

Data on the use of accelerator mass spectrometry (AMS) in conjunction with in vivo studies of macromolecular drugs are scarce. The present study shows the versatility of this technique when investigating the pharmacokinetics (PK) of a macromolecular drug candidate, a polybisphosphonate conjugate (ODX). The aforementioned is a polymer (molecular weight ~30 kDa) constituting a carbohydrate backbone with covalently linked ligands (aldendronate and aminoguanidine) and is intended for treatment of osteoporosis and the therapy of bone metastasis from prostate cancer.

Laboratory soft-x-ray microscope for cryotomography of biological specimens.

Soft-x-ray cryotomography allows quantitative and high-resolution three-dimensional imaging of intact unstained cells. To date, the method relies on synchrotron-radiation sources, which limits accessibility for researchers. Here we present a laboratory water-window microscope for cryotomography.

Development of a novel poly bisphosphonate conjugate for treatment of skeletal metastasis and osteoporosis.

Advanced stage prostate and breast cancer frequently metastasize to the skeleton (approximately 75%). An additional complication in these patients, that further affects the bones, is that their hormonal treatment, induces osteoporosis. Bisphosphonates (bpns) are standard drugs against osteoporosis and have been shown to have clinically significant anti-tumor effects.

Comparison of protein expression in two prostate cancer cell-lines, LNCaP and DU145, after treatment with somatostatin.

The mechanisms underlying prostate cancer progression are poorly understood. Proteins responsive to androgens may be involved in the development and progression of prostate cancer and the ultimate failure of androgen-ablation therapy. Therapy with somatostatin (sms) analogues could be a possible therapeutic alternative to chemotherapy in hormone refractory prostate cancer patients.

Sub-25-nm laboratory x-ray microscopy using a compound Fresnel zone plate.

Improving the resolution in x-ray microscopes is of high priority to enable future applications in nanoscience. However, high-resolution zone-plate optics often have low efficiency, which makes implementation in laboratory microscopes difficult. We present a laboratory x-ray microscope based on a compound zone plate.

The use of Butea superba (Roxb.) compared to sildenafil for treating erectile dysfunction.

Objective: To evaluate the effect of an extract of Butea superba (Roxb.) (BS) compared to sildenafil for treating erectile dysfunction (ED).

Patients And Methods: An open label study was carried out among 32 men with organic ED to evaluate the response on the International Index of Erectile Function 5 (IIEF-5) to BS, a 'natural health' product (100 mg), compared to 50 mg of sildenafil (a phosphodiesterase-5 inhibitor).

Polymer-conjugated guanidine is a potentially useful anti-tumor agent.

Guanidine compounds have important biochemical properties. Aminoguanidine, as an example, is an anti-oxidant, a nitric oxide synthase inhibitor (NOS) which prevents nitric oxide formation, and an inhibitor of advanced glycosylation end products (AGEs). As an anti-oxidant, aminoguanidine may affect the formation of atherosclerotic lesions through protection from LDL oxidation.

High-resolution computed tomography with a compact soft x-ray microscope.

Computed tomography based on high-resolution soft x-ray microscopy utilizes the natural contrast for biological specimens provided by the water window (lambda = 2.4 - 4.4 nm) and the high resolving power of zone plate objectives.

Incubation with somatostatin, 5-aza decitabine and trichostatin up-regulates somatostatin receptor expression in prostate cancer cells.

Somatostatin (SMS), binds to its specific receptors (SSTRs) and transduces growth inhibitory, anti-secretory and apoptotic signals. Several human cancers express SSTRs, including prostate cancer, and therefore SMS is of interest for anti-cancer therapy. DNA methylation and histone modifications are involved in normal cell development, gene imprinting and human carcinogenesis.