Mutual Regulation of Bcl-2 Proteins Independent of the BH3 Domain as Shown by the BH3-Lacking Protein Bcl-xAK

The BH3 domain of Bcl-2 proteins was regarded as indispensable for apoptosis induction and for mutual regulation of family members. We recently described Bcl-xAK, a proapoptotic splice product of the bcl-x gene, which lacks BH3 but encloses BH2, BH4 and a transmembrane domain. It remained however unclear, how Bcl-xAK may trigger apoptosis

Minicircle-oriP-IFNγ: A Novel Targeted Gene Therapeutic System for EBV Positive Human Nasopharyngeal Carcinoma

) in which the transgene expression was under the transcriptional regulation of oriP promoter.. Immunohistochemistry was used to detect the expression and the activity of the IFNγ in tumor sections. Our results demonstrated that mc-oriP vectors mediated comparable gene expression and anti-proliferative effect in the EBV-positive NPC cell line C666-1 compared to mc-CMV vectors. Furthermore, mc-oriP vectors exhibited much lower killing effects on EBV-negative cell lines compared to mc-CMV vectors. The targeted expression of mc-oriP vectors was inhibited by EBNA1-siRNA in C666-1. This selective expression was corroborated in EBV-positive and -negative tumor models. as a safe and highly effective targeted gene therapeutic system for the treatment of EBV positive NPC

CD95/Fas signaling in human melanoma cells: conditional expression of CD95L/FasL overcomes the intrinsic apoptosis resistance of malignant melanoma and inhibits growth and progression of human melanoma xenotransplants

The significance of CD95/Fas ligand expression by melanoma cells has remained a controversial matter in recent years. On the other hand, CD95 activation may represent a powerful tool for eliminating tumor cells. Here, we demonstrate expression of CD95 in 15/17 human melanoma cell lines analysed, but complete lack of CD95 ligand (CD95L). Overexpression of CD95 in a tetracycline-inducible expression system enhanced melanoma cell sensitivity to CD95 ligation but was unable to trigger apoptosis by itself. In clear contrast, all melanoma cells tested responded with increased apoptosis to conditional expression of CD95L (2–10-fold), both after transient and after stable transfection. Activation of caspase-8, Bid cleavage, cytochrome c release and caspase-3 activation followed after CD95L induction indicating a functional CD95-signaling cascade. CD95L was also able to enhance the proapoptotic effect of chemotherapeutics applied in parallel. Nude mouse experiments revealed that tumorigenicity was lost when melanoma xenografts were triggered to express CD95L. In addition, further progression of pre-existing melanomas was inhibited and even regression was seen after induction of CD95L expression. Due to these data, transfection of CD95L proofs as a highly efficient tool against melanoma cells in vitro and in vivo, and targeted expression of CD95L may thus represent a suitable strategy for melanoma therapy

Entwicklung und Qualifizierung eines einfachen Online-Qualitätsüberwachungssystems für das industrielle Laserstrahlhartlöten: Abschlussbericht zum Forschungsvorhaben "EQOS". Berichtszeitraum: 01.05.2008 bis 31.07.2011. Förderkennzeichen BMWi IN 7023 - 16IN0632-0633

Laser brazing makes it possible to join even thin-walled components at high speeds while producing seams with surface qualities. excellent For this reason, laser brazing is particularly suitable for joining car body parts which will be in direct view of the customer. Typical examples for this are automotive roof seams and two-piece tailgates. For these types of applications, the demands in regard to productivity, cost-effectiveness and quality are exceptionally high. Despite the use of sophisticated processing systems, sporadic seam irregularities like pores may still occur. In consequence, a wide range of post-process quality control systems is being used industrially to perform quality checks on laser brazed seams. However, this post-process approach to quality control rarely measures up to existing technological challenges. To offer a new solution for this challenge, the goal of the research project EQOS was to develop a new type of quality control system, which can detect several process and quality parameters online during the actual joining process. In a first step towards achieving this goal, the process mechanisms leading to the formation of seam defects were analyzed in detail. These analyses made it possible to reproduce different types of seam defects in a controlled environment for the purpose of testing, developing and qualifying the process control system. The analysis results also form a suitable foundation for developing new methods of detecting seam defects and new strategies of preventing seam defects. The next step in developing an online control system was the design of the optical system for performing the process control. For this purpose, two cameras operating in the visible (VIS) and near infrared (NIR) spectral range were coaxially integrated into the beam path of the laser processing head. This approach made it possible to monitor the process zone in both spectral ranges during the actual joining process. The third major work package of this project was the development of a software capable of automatically evaluating the camera images. For this purpose, different software modules with the capability of detecting individual defect types or process parameters were initially developed. These individual modules were subsequently successfully joined in a combined module for evaluating the seam quality. The combined result of these different tasks is a prototype system with online operating capabilities. It is based on an industrial brazing head with tactile seam guidance. The prototype was able to meet all technical requirements which were defined at the beginning of the project. Thus, the feasibility of performing a reliable online control of laser brazing processes could be successfully demonstrated. In conclusion, there is a wide range of potential applications for this type of system in the automotive sector. Additionally, the results of this project offer various opportunities for subsequent scientific research and industrial product development