Differential effects of hypoxia on motility using various in vitro models of lung adenocarcinoma.

Lung cancer is the leading cause of cancer-related death globally. Metastasis is the most common reason of mortality in which hypoxia is suggested to have a pivotal role. However, the effect of hypoxia on the metastatic potential and migratory activity of cancer cells is largely unexplored and warrants detailed scientific investigations.

Site-Selective Antibody Conjugation with Dibromopyrazines.

In recent years, antibody conjugates have evolved as state-of-the-art options for diagnostic and therapeutic applications. During site-selective antibody conjugation, incomplete rebridging of antibody chains limits the homogeneity of conjugates and calls for the development of new rebridging agents. Herein, we report a dibromopyrazine derivative optimized to reach highly homogeneous conjugates rapidly and with high conversion on rebridging of trastuzumab, even providing a feasible route for antibody modification in acidic conditions.

Role of Hypoxia and Rac1 Inhibition in the Metastatic Cascade.

The hypoxic condition has a pivotal role in solid tumors and was shown to correlate with the poor outcome of anticancer treatments. Hypoxia contributes to tumor progression and leads to therapy resistance. Two forms of a hypoxic environment might have relevance in tumor mass formation: chronic and cyclic hypoxia.

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.

Syndecan-1 Promotes Hepatocyte-Like Differentiation of Hepatoma Cells Targeting Ets-1 and AP-1.

Syndecan-1 is a transmembrane heparan sulfate proteoglycan which is indispensable in the structural and functional integrity of epithelia. Normal hepatocytes display strong cell surface expression of syndecan-1; however, upon malignant transformation, they may lose it from their cell surfaces. In this study, we demonstrate that re-expression of full-length or ectodomain-deleted syndecan-1 in hepatocellular carcinoma cells downregulates phosphorylation of ERK1/2 and p38, with the truncated form exerting an even stronger effect than the full-length protein.

Chemotherapy induced PRL3 expression promotes cancer growth via plasma membrane remodeling and specific alterations of caveolae-associated signaling.

Background: The outcome of cancer therapy is greatly defined by the ability of a tumor cell to evade treatment and re-establish its bulk mass after medical interventions. Consequently, there is an urgent need for the characterization of molecules affecting tumor reoccurrence. The phosphatase of regenerating liver 3 (PRL3) protein was recently emerged among the targets that could affect such a phenomenon.

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.

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.

No mutation but high mRNA expression of Coxsackie-Adenovirus Receptor was observed in both dilated and ischemic cardiomyopathy.

The most common causes of acute myocarditis and the possible consequence of dilated cardiomyopathy are virus infections. The receptor of the two most common viruses connected to these myocardial diseases was identified as Coxsackie-Adenovirus Receptor. The purpose of this study was to assess Coxsackie-Adenovirus Receptor mRNA expression in the myocardium and search for mutations in the Coxsackie-Adenovirus Receptor gene to compare dilated, inflammatory and ischemic cardiomyopathy with control group.

The role of viral infections in the development of dilated cardiomyopathy.

Enteroviruses (EVs) are the most frequent pathogens in myocarditis and in the subsequently developing dilated cardiomyopathy as well. Furthermore, persistence of other viruses might play a pathogenic role in the evolution from myocarditis to dilated cardiomyopathy. Explanted heart of 28 patients, who underwent heart transplantation were screened for EV, AdV3 and HHV6 sequences in order to assess the incidence of cardiac viral infection that may be implicated in the pathogenesis of cardiomyopathy, and estimate viral distribution in the myocardium.

Electron microscopic demonstration of Romhányi's aldehyde-bisulphite-toluidine blue (ABT)-topo-optical staining reaction.

Romhányi's aldehyde-bisulphite-toluidine blue (ABT) topo-optical reaction was checked electron microscopically. The reaction product was found localized on the sarcolemma membrane and intercalated disc. The findings suggest that the topo-optical ABT-reaction is suitable for molecular analysis.

[Molecular biological virus identification in dilated cardiomyopathy].

Unlabelled: Enteroviruses have been considered to be the most common cause of acute myocarditis and possible consequence of dilated cardiomyopathy. Some publications shed light to the role of other viruses in this disease as well. Our molecular investigation has demonstrated that adeno- and herpes viruses might also frequently occur in dilated cardiomyopathy.

[Proteoglycans in the liver].

Proteoglycans are macromolecules formed by a protein core to which sugar chains are covalently attached. They are present on the cell surface and in the ECM of living things. In normal liver syndecan-1 is the dominant transmembrane proteoglycan, trace amounts of ECM proteoglycans are in the stromal components.