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Objective: Glioblastoma (GBM) is the most malignant brain tumor in adults. Despite the standard therapy including surgical resection and adjuvant combined radio/chemotherapy, the average survival of GBM patients is still poor. Since the crosstalk between residual tumor cells and the surrounding [for full text, please go to the a.m. URL]

Pancreatic ductal adenocarcinoma (PDAC) is amongst the most fatal malignancies and its development is highly associated with inflammatory processes such as chronic pancreatitis (CP). Since the succinate dehydrogenase subunit B (SDHB) is regarded as tumor suppressor that is lost during cancer development, this study investigated the impact of M1-macrophages as part of the inflammatory microenvironment on the expression as well as function of SDHB in benign and premalignant pancreatic ductal epithelial cells (PDECs). Immunohistochemical analyses on pancreatic tissue sections from CP patients and control individuals revealed a stronger SDHB expression in ducts of CP tissues being associated with a greater abundance of macrophages compared to ducts in control tissues. Accordingly, indirect co-culture with M1-macrophages led to clearly elevated SDHB expression and SDH activity in benign H6c7-pBp and premalignant H6c7-kras PDECs. While siRNA-mediated SDHB knockdown in these cells did not affect glucose and lactate uptake after co-culture, SDHB knockdown significantly promoted PDEC growth which was associated with increased proliferation and decreased effector caspase activity particularly in co-cultured PDECs. Overall, these data indicate that SDHB expression and SDH activity are increased in PDECs when exposed to pro-inflammatory macrophages as a counterregulatory mechanism to prevent excessive PDEC growth triggered by the inflammatory environment.

Claudia Geismann,1 Alexander Arlt,1 Susanne Sebens,2 Heiner Schäfer11Laboratory of Molecular Gastroenterology, Department of Internal Medicine I, 2Inflammatory Carcinogenesis Research Group, Institute of Experimental Medicine, Universitätsklinikum Schleswig-Holstein Campus Kiel, Kiel, GermanyAbstract: Nrf2 has gained great attention with respect to its pivotal role in cell and tissue protection. Primarily defending cells against metabolic, xenobiotic and oxidative stress, Nrf2 is essential for maintaining tissue integrity. Owing to these functions, Nrf2 is regarded as a promising drug target in the chemoprevention of diseases, including cancer. However, much evidence has accumulated that the beneficial role of Nrf2 in cancer prevention essentially depends on the tight control of its activity. In fact, the deregulation of Nrf2 is a critical determinant in oncogenesis and found in many types of cancer. Therefore, amplified Nrf2 activity has profound effects on the phenotype of tumor cells, including radio/chemoresistance, apoptosis protection, invasiveness, antisenescence, autophagy deficiency, and angiogenicity. The deregulation of Nrf2 can result from various epigenetic and genetic alterations directly affecting Nrf2 control or from the complex interplay of Nrf2 with numerous oncogenic signaling pathways. Additionally, alterations of the cellular environment, eg, during inflammation, contribute to Nrf2 deregulation and its persistent activation. Therefore, the status of Nrf2 as anti- or protumorigenic is defined by many different modalities. A better understanding of these modalities is essential for the safe use of Nrf2 as an activation target for chemoprevention on the one hand and as an inhibition target in cancer therapy on the other. The present review mainly addresses the conditions that promote the oncogenic function of Nrf2 and the resulting consequences providing the rationale for using Nrf2 as a target structure in cancer therapy.Keywords: xenobiotic and oxidative stress, tumorigenesis, cancer therapy, transcription factor, carcinogen

Dormancy has been defined as "one of two prerequisites for life" and plays a fundamental role in all stages of tumor evolution. Described as a reversible quiescent cellular stage, tumor dormancy allows adaptation and survival of tumor cells under hostile conditions, for example, oxidative or metabolic stress, inflammatory processes or exposure to anticancer therapies. Thus, dormant tumor cells are fundamental for the fitness of the entire tumor cell population assuring and promoting tumor evolution so that dormancy has been postulated as a novel hallmark of cancer. Besides the tumoral microenvironment, epigenetic, and metabolic alterations seem to be critical determinants for the entry in and exit from dormancy. However, the underlying mechanisms are still poorly understood. In fact, dormant life-history phases or stages are widespread among living organisms representing a highly effective strategy to survive unfavorable environmental conditions and thus ensuring persistence during evolution. Integrating an evolutionary perspective in the investigation of tumor dormancy will help us to understand the plasticity of the proliferative phenotype of tumor cells and how this promotes tumor evolution. Incorporating evolutionary methods into cancer research and addressing new evolutionary questions may help to explain the phenomenon of dormancy in tumor evolution leading to improved cancer therapies. © 2017 Elsevier Inc. All rights reserved.

Objective: Malignant glioblastomas have a median survival time of less than one year which is mainly due to aggressive relapses after therapeutic treatment. They achieve their progressive character via epithelial-to-mesenchymal transition (EMT); however, comparative surveys on EMT in primary glioblastomas[for full text, please go to the a.m. URL], 66. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Objective: Glioblastomas are highly malignant brain tumors marked by poor prognosis and unsatisfactory response to treatments such as radio- and chemotherapy. The neural cell adhesion molecule L1CAM is expressed in various types of cancers including glioblastoma and has been demonstrated to facilitate[for full text, please go to the a.m. URL], 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH)

The constitutive activation of the transcription factor nuclear-factor kappa B (NF-kappaB) is a hallmark of many highly malignant tumours such as the pancreatic ductal adenocarcinoma and accounts for profound chemoresistance. Inhibition of NF-kappaB activation has been shown to be a useful strategy for increasing the sensitivity towards cytostatic drug treatment in vitro and in vivo. Moreover, various pharmacological substances (e.g. thalidomide, bortezomib, sulphasalazine) have already entered clinical studies partially showing promising results for certain types of cancer. Further studies will be needed, in particular for pancreatic ductal adenocarcinoma, to evaluate the therapeutic efficacy of appropriate combinations of a NF-kappaB inhibitor and cytostatic drugs.