Dual Inhibitors of AChE and BACE-1 for Reducing Aβ in Alzheimer's Disease: From In Silico to In Vivo.

Alzheimer's disease (AD) is a complex and widespread condition, still not fully understood and with no cure yet. Amyloid beta (Aβ) peptide is suspected to be a major cause of AD, and therefore, simultaneously blocking its formation and aggregation by inhibition of the enzymes BACE-1 (β-secretase) and AChE (acetylcholinesterase) by a single inhibitor may be an effective therapeutic approach, as compared to blocking one of these targets or by combining two drugs, one for each of these targets. We used our ISE algorithm to model each of the AChE peripheral site inhibitors and BACE-1 inhibitors, on the basis of published data, and constructed classification models for each.

Cell type-dependent HIF1 α-mediated effects of hypoxia on proliferation, migration and metastatic potential of human tumor cells.

Tumor hypoxia promotes neoangiogenesis and contributes to the radio- and chemotherapy resistant and aggressive phenotype of cancer cells. However, the migratory response of tumor cells and the role of small GTPases regulating the organization of cytoskeleton under hypoxic conditions have yet to be established. Accordingly, we measured the proliferation, migration, RhoA activation, the mRNA and protein levels of hypoxia inducible factor-1alpha (HIF-1α) and three small G-proteins, Rac1, cdc42 and RhoA in a panel of five human tumor cell lines under normoxic and hypoxic conditions.

Improved in vivo antitumor effect of a daunorubicin - GnRH-III bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice.

Compared to classical chemotherapy, peptide-based drug targeting is a promising therapeutic approach for cancer, which can provide increased selectivity and decreased side effects to anticancer drugs. Among various homing devices, gonadotropin-releasing hormone-III (GnRH-III) peptide represents a suitable targeting moiety, in particular in the treatment of hormone independent tumors that highly express GnRH receptors (e.g.

[Studying the tumor growth inhibitory effect of modified GnRH-III-anthracycline bioconjugates in subcutaneous vs. orthotopic models in vivo].

Targeted tumor therapy is a perspective procedure to specifically destroy the cancer tissues with eliminating or at least decreasing the side effects of anticancer drugs. For this purpose the drug molecule is attached to a targeting moiety (e.g.

N-Glycosylation analysis of formalin fixed paraffin embedded samples by capillary electrophoresis.

In this study, N-linked glycans from intact, formalin treated and formalin fixed paraffin embedded (FFPE) standard glycoproteins, human serum and mouse tumor tissue samples were investigated in respect to their susceptibility for formaldehyde treatment mediated changes. FFPE samples were first deparaffinized, followed by solubilization in radioimmunoprecipitation assay buffer and treated with PNGase F for N-glycan release. The released glycans were labeled with a charged fluorophore and analyzed by capillary electrophoresis with laser induced fluorescent detection.

Boyden chamber-based method for characterizing the distribution of adhesions and cytoskeletal structure in HT1080 fibrosarcoma cells.

A 2D model was previously presented that describes the gliding motility of human fibrosarcoma cells. The model was based on the observation that adhesions are present only on the outer rim of the leading lamella of the semicircular cell. The present model describes the organization of adhesions and the cytoskeleton of migrating HT1080 fibrosarcoma and LX2 hepatic stellate cells in three dimensions.