Met degradation by SAIT301, a Met monoclonal antibody,reduces the invasion and migration of nasopharyngeal cancer cells via inhibition of EGR-1 expression

Nasopharyngeal carcinoma (NPC) is a common malignant tumor with high invasive and metastatic potential. The hepatocyte growth factor (HGF)-Met signaling pathway has a critical role in mediating the invasive growth of many different types of cancer, including head and neck squamous cell carcinoma. HGF also stimulates NPC cell growth and invasion in the cell line model. In this study, we determined the inhibitory effect of Met, using a Met-targeting monoclonal antibody (SAIT301), on the invasive and growth potential of NPC cell lines. Met inhibition by SAIT301 resulted in highly significant inhibition of cell migration and invasion in both the HONE1 and HNE1 cell lines. In addition, we also found that co-treatment of SAIT301 and HGF decreased the anchorage-independent growth induced by HGF in HNE1 cell lines. After SAIT301 treatment, Met, together with its downstream signaling proteins, showed downregulation of p-Met and p-ERK, but not p-AKT, in both HONE1 and HNE1 cell lines. Interestingly, we found that HGF treatment of NPC cell lines induced early growth response protein (EGR-1) expression, which is involved in cell migration and invasion. In addition, co-treatment with SAIT301 and HGF inhibited the HGF-induced expression of EGR-1. Next, knockdown of EGR-1 using small-interfering RNA inhibited HGF-induced cell invasion in NPC cell lines, suggesting that the expression level of EGR-1 is important in HGF-induced cell invasion of NPC cells. Therefore, the results support that SAIT301 inhibited Met activation as well as the downstream EGR-1 expression and could have therapeutic potential in NPC. Taken together, we suggest that Met is an anticancer therapeutic target for NPC that warrants further investigation and clinical trials and SAIT301 may be a promising tool for NPC therapy.     

Biochemical and Autoradiographic Study of Cerebral Protein Synthesis with [18F]- and [14C]Fluorophenylalanine

Fluorine-18-labeled ortho or para isomers of L-fluorophenylalanine were used in double-label experiments together with L-[3H]phenylalanine for amino acid incorporation into cerebral proteins of Mongolian gerbil brain. It was demonstrated by qualitative regional comparison of the 18F and 3H autoradiographic images that L-p-[18F]fluorophenylalanine is incorporated into proteins and exhibits a regional cerebral protein synthesis pattern. To a minor extent, L-p-fluorophenyl[3-14C]alanine and L-o-[18F]fluorophenylalanine are hydroxylated in vivo to form labeled tyrosine or tyrosine analogues that are incorporated into cerebral proteins as well. The advantage and validity of the application of L-p-[18F]fluorophenylalanine with positron emission tomography for noninvasive studies of cerebral protein synthesis in humans are evaluated on the basis of an experimental animal approach.     

Evaluation of vasogenic edema in experimental brain tumors by cathodoluminescence and fluorescence microscopy

Summary Cathodoluminescence and fluorescence microscopy have been used to study vasogenic edema in experimentally induced brain tumors in rats. Both methods are suited for the demonstration of FITC- or TRITC-coupled antiserum, and thus allow the evaluation of serum protein extravasation. Cathodoluminescence is more time consuming and laborious than fluorescence microscopy, but it has distinct advantages: Contrast enhancement improves the differentiation between certain cell types, and the higher resolution of the scanning electron microscope allows the identification of subcellular regions which cannot be recognized by conventional fluorescence microscopy.     

Effects of electromagnetic radiation of mobile phones on the central nervous system

With the increasing use of mobile communication, concerns have been expressed about the possible interactions of electromagnetic radiation with the human organism and, in particular, the brain. The effects on neuronal electrical activity, energy metabolism, genomic responses, neurotransmitter balance, blood-brain barrier permeability, cognitive function, sleep, and various brain diseases including brain tumors are reviewed. Most of the reported effects are small as long as the radiation intensity remains in the nonthermal range, and none of the research reviewed gives an indication of the mechanisms involved at this range. However, health risks may evolve from indirect consequences of mobile telephony, such as the sharply increased incidence rate of traffic accidents caused by telephony during driving, and possibly also by stress reactions which annoyed bystanders may experience when cellular phones are used in public places. These indirect health effects presumably outweigh the direct biological perturbations and should be investigated in more detail in the future.     

Pathophysiology and Therapy of Experimental Stroke

1. Stroke is the neurological evidence of a critical reduction of cerebral blood flow in a circumscribed part of the brain, resulting from the sudden or gradually progressing obstruction of a large brain artery. Treatment of stroke requires the solid understanding of stroke pathophysiology and involves a broad range of hemodynamic and molecular interventions. This review summarizes research that has been carried out in many laboratories over a long period of time, but the main focus will be on own experimental research.2. The first chapter deals with the hemodynamics of focal ischemia with particular emphasis on the collateral circulation of the brain, the regulation of blood flow and the microcirculation. In the second chapter the penumbra concept of ischemia is discussed, providing a detailed list of the physiological, biochemical and structural viability thresholds of ischemia and examples of how these thresholds can be applied for imaging the penumbra. The third chapter summarizes the pathophysiology of infarct progression, focusing on the role of peri-infarct depolarisation, the multitude of putative molecular injury pathways, brain edema and inflammation. Finally, the fourth chapter provides an overview of currently discussed therapeutic approaches, notably the effect of mechanical or thrombolytic reperfusion, arteriogenesis, pharmacological neuroprotection, ischemic preconditioning and regeneration.3. The main emphasis of the review is placed on the balanced differentiation between hemodynamic and molecular factors contributing to the manifestation of ischemic injury in order to provide a rational basis for future therapeutic interventions.