Inhibition of FAK kinase activity preferentially targets cancer stem cells.

Because cancer stem cells (CSCs) have been implicated in chemo-resistance, metastasis and tumor recurrence, therapeutic targeting of CSCs holds promise to address these clinical challenges to cancer treatment. VS-4718 and VS-6063 are potent inhibitors of focal adhesion kinase (FAK), a non-receptor tyrosine kinase that mediates cell signals transmitted by integrins and growth factor receptors. We report here that inhibition of FAK kinase activity by VS-4718 or VS-6063 preferentially targets CSCs, as demonstrated by a panel of orthogonal CSC assays in cell line models and surgically resected primary breast tumor specimens cultured .

GC-MS analysis of the designer drug α-pyrrolidinovalerophenone and its metabolites in urine and blood in an acute poisoning case.

α-Pyrrolidinovalerophenone (α-PVP) is a synthetic cathinone belonging to the group of "second generation" pyrrolidinophenones that becomes more and more popular as a designer psychostimulant. Here we provide toxicological analytical support for a severe poisoning with α-PVP. Serum and urine samples that were sent to our laboratory were subjected to a general unknown screening procedure.

PI3K/mTOR dual inhibitor VS-5584 preferentially targets cancer stem cells.

Cancer stem cells (CSC) have been implicated in disease recurrence, metastasis, and therapeutic resistance, but effective targeting strategies for these cells are still wanting. VS-5584 is a potent and selective dual inhibitor of mTORC1/2 and class I PI 3-kinases. Here, we report that VS-5584 is up to 30-fold more potent in inhibiting the proliferation and survival of CSC compared with non-CSC in solid tumor cell populations.

Merlin deficiency predicts FAK inhibitor sensitivity: a synthetic lethal relationship.

The goal of targeted therapy is to match a selective drug with a genetic lesion that predicts for drug sensitivity. In a diverse panel of cancer cell lines, we found that the cells most sensitive to focal adhesion kinase (FAK) inhibition lack expression of the neurofibromatosis type 2 (NF2) tumor suppressor gene product, Merlin. Merlin expression is often lost in malignant pleural mesothelioma (MPM), an asbestos-induced aggressive cancer with limited treatment options.

Bupropion interference with immunoassays for amphetamines and LSD.

A 50-year-old male patient suddenly had lost consciousness, although he had previously been healthy. On arrival at hospital seizures arose. The authors investigated a urine sample of the patient, and performed toxicological drug screening with immunochemical Cloned Enzyme Donor Immunoassay (CEDIA) assays.

Drug screening in urine by cloned enzyme donor immunoassay (CEDIA) and kinetic interaction of microparticles in solution (KIMS): a comparative study.

Two commercially available drug-screening assays were evaluated: the Roche kinetic interaction of microparticles in solution (KIMS) assay and the Microgenics cloned enzyme donor immunoassay (CEDIA). Urine samples from known drug-abuse patients were analyzed for amphetamines, barbiturates, benzodiazepines, benzoylecgonine, cannabinoids, LSD, methadone and opiates. Samples with discordant findings for the two assays were analyzed by gas chromatography/mass spectrometry (GC/MS) or gas chromatography/electron capture detection (GC/ECD).

Magnesium absorption from mineral waters of different magnesium content in healthy subjects.

Objective: To assess the absorption of magnesium (Mg) from mineral waters of different Mg content in comparison to low mineralized water and a Mg capsule.

Design: Randomized, controlled, double- blind trial in a crossover design with an additional control with a Mg capsule.

Setting: Institute of Balneology and Medical Climatology, Medical School of Hanover, Germany.

[Genital histoplasmosis. Presentation of a clinical case].

Objectives: On December 1905 Darling, resident histopathologist on the Panama Channel area, observed a parasite in the large mononuclear cells of different organs. Negroni in 1914 described the first Argentinean case. Lung, oral, nasal, and laryngeal involvement are common.