Stoffenmanager Nano version 1.0: a web-based tool for risk prioritization of airborne manufactured nano objects.

Stoffenmanager Nano (version 1.0) is a risk-banding tool developed for employers and employees to prioritize health risks occurring as a result of exposure to manufactured nano objects (MNOs) for a broad range of worker scenarios and to assist implementation of control measures to reduce exposure levels. In order to prioritize the health risks, the Stoffenmanager Nano combines the available hazard information of a substance with a qualitative estimate of potential for inhalation exposure.

Enriching lipid nanovesicles with short-chain glucosylceramide improves doxorubicin delivery and efficacy in solid tumors.

For amphiphilic anticancer drugs, such as the anthracyclin doxorubicin (Dox), uptake by tumor cells involves slow diffusion across the plasma membrane, a limiting factor in clinical oncology. Previously, we discovered that preinsertion of short-chain sphingolipids such as N-octanoyl-glucosylceramide (GC) in the tumor cell membrane enhances cellular Dox uptake. In the present study, we apply this strategy in vitro and in vivo by coadministering GC and Dox in a lipid nanovesicle (LNV).

Alkylphospholipids inhibit capillary-like endothelial tube formation in vitro: antiangiogenic properties of a new class of antitumor agents.

Synthetic alkylphospholipids (APLs), such as edelfosine, miltefosine and perifosine, constitute a new class of antineoplastic compounds with various clinical applications. Here we have evaluated the antiangiogenic properties of APLs. The sensitivity of three types of vascular endothelial cells (ECs) (bovine aortic ECs, human umbilical vein ECs and human microvascular ECs) to APL-induced apoptosis was dependent on the proliferative status of these cells and correlated with the cellular drug incorporation.

Lipid rafts and metabolic energy differentially determine uptake of anti-cancer alkylphospholipids in lymphoma versus carcinoma cells.

Perifosine is a member of the class of synthetic alkylphospholipids (APLs) and is being evaluated as anti-cancer agent in several clinical trials. These single-chain APLs accumulate in cellular membranes and disturb lipid-dependent signal transduction, ultimately causing apoptosis in a variety of tumor cells. The APL prototype edelfosine was previously found to be endocytosed by S49 mouse lymphoma cells via lipid rafts.

A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells.

Single-chain alkylphospholipids, unlike conventional chemotherapeutic drugs, act on cell membranes to induce apoptosis in tumor cells. We tested four different alkylphospholipids, i.e.

Rationale and clinical application of alkylphospholipid analogues in combination with radiotherapy.

Concurrent treatment with radiotherapy and chemotherapy has emerged as an effective strategy to improve clinical outcome of cancer. In addition to combining radiation with classical anticancer agents, several new biological response modifiers are under investigation in pre-clinical and clinical studies. Synthetic alkylphospholipids are anticancer agents that in contrast to most anticancer drugs, do not target DNA, but insert in the plasma membrane and subsequently induce a broad range of biological effects, ultimately leading to cell death.

TRAIL enhances efficacy of radiotherapy in a p53 mutant, Bcl-2 overexpressing lymphoid malignancy.

Background And Purpose: Resistance to apoptosis is a contributing factor in the response to radiotherapy. Aim of this study was to evaluate whether TRAIL--in a soluble isoleucine zippered form--enhances the cytotoxic effect of irradiation on tumour cells with a blockade in the mitochondrial apoptosis route and/or a dysfunctional p53 pathway.

Materials And Methods: The p53 mutant human T acute lymphoblastic leukemia line Jurkat transduced with the Bcl-2 gene was used as model system in vitro and in a subcutaneous transplant setting in immunodeficient mice.

Phase I and pharmacokinetic study of combined treatment with perifosine and radiation in patients with advanced solid tumours.

Purpose: Perifosine is an orally applicable, membrane-targeted alkylphosphocholine analogue with antitumour activity and radiosensitising properties in preclinical models. The purpose of this phase I study was to determine the feasibility and tolerability of concurrent daily perifosine and radiation in patients with advanced cancer.

Patients And Methods: Starting dose of perifosine was 50 mg/day; dose escalation was in steps of 50mg.

Radiosensitization of squamous cell carcinoma by the alkylphospholipid perifosine in cell culture and xenografts.

Purpose: Combined modality treatment has improved outcome in various solid tumors. Besides classic anticancer drugs, a new generation of biological response modifiers has emerged that increases the efficacy of radiation. Here, we have investigated whether perifosine, an orally applicable, membrane-targeted alkylphospholipid, enhances the antitumor effect of radiation in vitro and in vivo.

Coformulated N-octanoyl-glucosylceramide improves cellular delivery and cytotoxicity of liposomal doxorubicin.

The anticancer agent doxorubicin is in certain cases administered as a long-circulating liposomal formulation. Due to angiogenesis-related structural abnormalities in the endothelial lining of many neoplasms, these complexes tend to extravasate and accumulate in the tumor stroma. However, delivery of doxorubicin is still not optimal since liposomes are not taken up directly by tumor cells.

Tumor and normal tissue pharmacokinetics of perifosine, an oral anti-cancer alkylphospholipid.

Clinical use of anti-cancer alkylphospholipids is limited by gastrointestinal toxicity. However, new interest has emerged since it was shown that these drugs enhance the cytotoxic effect of conventional chemotherapy and radiotherapy in preclinical models. The aim of this study was to characterize the pharmacokinetic profile of perifosine, an oral analog of alkylphosphocholine (APC), and to compare in vitro drug uptake with in vivo drug accumulation in three human-derived squamous cell carcinomas (A431, HNXOE and KB).