A paired comparison between glioblastoma "stem cells" and differentiated cells.

Cancer stem cells (CSC) have been postulated to be responsible for the key features of a malignancy and its maintenances, as well as therapy resistance, while differentiated cells are believed to make up the rapidly growing tumour bulk. It is therefore important to understand the characteristics of those two distinct cell populations in order to devise treatment strategies which effectively target both cohorts, in particular with respect to cancers, such as glioblastoma. Glioblastoma is the most common primary brain tumour in adults, with a mean patient survival of 12-15 months. Importantly, therapeutic improvements have not been forthcoming in the last decade. In this study we compare key features of three pairs of glioblastoma cell populations, each pair consisting of stem cell-like and differentiated cells derived from an individual patient. Our data suggest that while growth rates and expression of key survival- and apoptosis-mediating proteins are more similar according to differentiation status than genetic similarity, we found no intrinsic differences in response to standard therapeutic interventions, namely exposure to radiation or the alkylating agent temozolomide. Interestingly, we could demonstrate that both stem cell-like and differentiated cells possess the ability to form stem cell-containing tumours in immunocompromised mice and that differentiated cells could potentially be dedifferentiated to potential stem cells. Taken together our data suggest that the differences between tumour stem cell and differentiated cell are particular fluent in glioblastoma.

[Myocardial Infarction in an Athlete]. / Myokardinfarkt bei einem Sportler.

Myocardial Infarction in an Athlete Abstract. We report the case of a male athlete with a myocardial infarction caused by intracoronary thrombus formation, which was associated with prior cannabis consumption. Cannabis is a rare cause of myocardial infarction and is poorly recognized as a cardiovascular risk factor. Because of the ongoing process of marijuana legalization in many countries, there is concern about an increasing number of cannabis-related myocardial infarctions especially in young patients. Several pathophysiological mechanisms have been proposed and warrant further investigation.

Radiation and Brain Tumors: An Overview.

The use of radiation is an essential part of both modern cancer diagnostic assessment and treatment. Next-generation imaging devices create 3D visualizations, allowing for better diagnoses and improved planning of precision treatment. This is particularly important for primary brain cancers such as diffuse intrinsic pontine glioma or the most common primary brain tumor, glioblastoma, because radiotherapy is often the only treatment modality that offers a significant improvement in survival and quality of life. In this review, we give an overview of the different imaging techniques and the historic role of radiotherapy and its place in modern cancer therapy. Finally, we discuss three key areas of risks associated with the use of ionizing radiation: (1) brain tumor induction mainly as a consequence of the diagnostic use of radiation; (2) cognitive decline as a consequence of treating childhood brain tumors as an example of long term consequences often neglected in favor of highlighting secondary primary cancers; and (3) pro-proliferative and pro-invasive alterations that occur in tumor cells that survive radiotherapy. Throughout the discussion, we highlight areas of potential future research.

Inhibition of PI3K signalling increases the efficiency of radiotherapy in glioblastoma cells.

Glioblastoma, the most common primary brain tumour, is also considered one of the most lethal cancers per se. It is highly refractory to therapeutic intervention, as highlighted by the mean patient survival of only 15 months, despite an aggressive treatment approach, consisting of maximal safe surgical resection, followed by radio- and chemotherapy. Radiotherapy, in particular, can have effects on the surviving fractions of tumour cells, which are considered adverse to the desired clinical outcome: It can induce increased cellular proliferation, as well as enhanced invasion. In this study, we established that differentiated glioblastoma cells alter their DNA repair response following repeated exposure to radiation and, therefore, high single-dose irradiation (SD-IR) is not a good surrogate marker for fractionated dose irradiation (FD-IR), as used in clinical practice. Integrating irradiation into a combination therapy approach, we then investigated whether the pharmacological inhibition of PI3K signalling, the most abundantly activated survival cascade in glioblastoma, enhances the efficacy of radiotherapy. Of note, treatment with GDC-0941, which blocks PI3K-mediated signalling, did not enhance cell death upon irradiation, but both treatment modalities functioned synergistically to reduce the total cell number. Furthermore, GDC-0941 not only prevented the radiation-induced increase in the motility of the differentiated cells, but further reduced their speed below that of untreated cells. Therefore, combining radiotherapy with the pharmacological inhibition of PI3K signalling is a potentially promising approach for the treatment of glioblastoma, as it can reduce the unwanted effects on the surviving fraction of tumour cells.

Cell Death Induction in Cancer Therapy - Past, Present, and Future.

The induction of apoptosis, a physiological type of cell death, is currently the primary therapeutic aim of most cancer therapies. As resistance to apoptosis is an early hallmark of developing cancer, the success of this treatment strategy is already potentially compromised at treatment initiation. In this review, we discuss the tumor in Darwinian terms and describe it as a complex, yet highly unstable, ecosystem. Current therapeutic strategies often focus on directly killing the dominant subclone within the population of mutated cancer cells while ignoring the subclonal complexity within the ecosystem tumor, the complexity of the direct tumor/ microenvironment interaction and the contribution of the ecosystem human - that is, the global environment which provides the tumor with both support and challenges. The Darwinian view opens new possible therapeutic interventions, such as the disruption of the microenvironment by targeting nonmutated cells within the tumor or the interaction points of mutant tumor cells with their environment, and it forces us to reevaluate therapeutic endpoints. It is our belief that a central future challenge of apoptosis-inducing therapies will be to understand better under which preconditions which treatment strategy and which therapeutic endpoint will lead to the highest quality and quantity of a patient's life.