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Drug-adapted Cancer Cell Lines Reveal Drug-induced Heterogeneity and Enable the Identification of Biomarker Candidates for the Acquired Resistance Setting
Survivin is a drug target and the survivin suppressant YM155 a drug candidate for high-risk neuroblastoma. Findings from one YM155-adapted subline of the neuroblastoma cell line UKF-NB-3 had suggested that increased ABCB1 (mediates YM155 efflux) levels, decreased SLC35F2 (mediates YM155 uptake) levels, decreased survivin levels, and TP53 mutations indicate YM155 resistance. Here, the investigation of ten additional YM155-adapted UKF-NB-3 sublines only confirmed the roles of ABCB1 and SLC35F2. However, cellular ABCB1 and SLC35F2 levels did not indicate YM155 sensitivity in YM155-naïve cells, as indicated by drug response data derived from the Cancer Therapeutics Response Portal (CTRP) and th...
Dexamethasone Treatment Limits Efficacy of Radiation, But Does Not Interfere with Glioma Cell Death Induced by Tumor Treating Fields
Background: Dexamethasone (Dex) is the most common corticosteroid to treat edema in glioblastoma (GBM) patients. Recent studies identified the addition of Dex to radiation therapy (RT) to be associated with poor survival. Independently, Tumor Treating Fields (TTFields) provides a novel anti-cancer modality for patients with primary and recurrent GBM. Whether Dex influences the efficacy of TTFields, however, remains elusive. Methods: Human GBM cell lines MZ54 and U251 were treated with RT or TTFields in combination with Dex and the effects on cell counts and cell death were determined via flow cytometry. We further performed a retrospective analysis of GBM patients with TTFields treatment +/-...
CHRDL1 Regulates Stemness in Glioma Stem-like Cells
Glioblastoma (GBM) still presents as one of the most aggressive tumours in the brain, which despite enormous research efforts, remains incurable today. As many theories evolve around the persistent recurrence of this malignancy, the assumption of a small population of cells with a stem-like phenotype remains a key driver of its infiltrative nature. In this article, we research Chordin-like 1 (CHRDL1), a secreted protein, as a potential key regulator of the glioma stem-like cell (GSC) phenotype. It has been shown that CHRDL1 antagonizes the function of bone morphogenic protein 4 (BMP4), which induces GSC differentiation and, hence, reduces tumorigenicity. We, therefore, employed two previousl...
Glioblastoma: State of the Art and Future Perspectives
Glioblastoma is an aggressive incurable primary tumor of the central nervous system. Median overall survival is in the range of 1.5 years even in selected clinical trials populations. Many features contribute to this therapeutic challenge including high intratumoral and intertumoral heterogeneity, resistance to therapy, migration and invasion, immunosuppression. With the access of novel highthroughput technologies, significant progress has been made to understand molecular and immunological signatures underlying the pathology of glioblastoma. Clinical trial designs have shifted from investigating broad “one-for-all” treatment approaches to precision oncology designs. The collection of contributions in this book aim at providing researchers and clinicians an update on different aspects of glioblastoma, i.e. progress in basic, preclinical and clinical research.
The Impact of Tumor Biology on Cancer Treatment and Multidisciplinary Strategies
Te rapidly changing concepts in radiation oncology with the development of more precise - strumentation for delivery of radiation therapy and a greater emphasis on hypofractionation technologies require a very intimate knowledge of tumor biology and the infuence of various biologic factors on dose distribution within the tumor in terms of homogeneity as well as prev- tion of any late efects on normal tissue surrounding the tumor itself. Not only are these major factors in clinical practice but also the known factors of inhomogeneity of cancer cells, the impact of microenvironment in terms of radiation efect, and host factors make it mandatory to design therapeutic strategies to improve the o...
Radiation and the Immune System: Current Knowledge and Future Perspectives
For long, high dose ionizing radiation was considered as a net immune suppressing agent, as shown, among others, by the exquisite radiosensitivity of the lymphoid system to radiation-induced cell killing. However, recent advances in radiobiology and immunology have made this picture more complex. For example, the recognition that radiation-induced bystander effects, share common mediators with various immunological signalling processes, suggests that they are at least partly immune mediated. Another milestone was the finding, in the field of onco-immunology, that local tumor irradiation can modulate the immunogenicity of tumor cells and the anti-tumor immune responsiveness both locally, in t...
Cardiac Cell Biology
Cardiac cell biology has come of age. Recognition of activated or modified signaling molecules by specific antibodies, new selective inhibitors, and fluorescent fusion tags are but a few of the tools used to dissect signaling pathways and cross-talk mechanisms that may eventually allow rational drug design. Understanding the regulation of cardiac hypertrophy in all its complexity remains a fundamental goal of cardiac research. Since the advancement of adenovirally mediated gene transfer, transfection efficiency is no longer a limiting factor in the study of cardiomyocytes. A limiting factor in considering cell transplantion as a strategy to repair the damaged heart is cell availability at the right time. Cardiac gap junctions, intercellular communication channels that allow electrical and metabolic coupling and play an important role in arrhythmogenesis are now understood to be exquisite sensors of cardiac change. The reports in this volume incLude elegant studies that made use of cutting edge technological advances and many specialized reagents to address these issues.
Radiation-induced effects and the immune system
Numerous developments in molecular biology have led to an explosive growth in the knowledge underlying mechanisms of carcinogenesis, cell signalling, tumor progression and development of metastasis. However, cure of cancer is still hampered by the inherited capacity of tumors to become resistant to standard therapies, to metastasize from their initial location and to proliferate in other tissue compartments. Radiotherapy is one of the main treatment modalities to achieve locoregional tumor control. However, the treatment of distant metastases further remains to be a challenge. In this special topic we are interested to elucidate immunological aspects which are initiated and affected by radio...
Insights in Neuro-Oncology and Neurosurgical Oncology: 2021
We are now entering the third decade of the 21st Century, and, especially in the last years, the achievements made by scientists have been exceptional, leading to major advancements in the fast-growing field of Oncology. Frontiers has organized a series of Research Topics to highlight the latest advancements in research across the field of Oncology, with articles from the Associate Members of our accomplished Editorial Boards. This editorial initiative of particular relevance, led by Prof. David Eisenstat, Specialty Chief Editor of the Neuro-Oncology and Neurosurgical Oncology section, together with Prof. Erik Sulman, focused on new insights, novel developments, current challenges, latest di...
PLGA Based Drug Carrier and Pharmaceutical Applications
Poly(lactic-co-glycolic acid) (PLGA) is one of the most successful polymers used for producing therapeutic devices, such as drug carriers (DC). PLGA is one of the few polymers that the Food and Drug Administration (FDA) has approved for human administration due to its biocompatibility and biodegradability. In recent years, DC produced with PLGA has gained enormous attention for its versatility in transporting different type of drugs, e.g., hydrophilic or hydrophobic small molecules, or macromolecules with a controlled drug release without modifying the physiochemical properties of the drugs. These drug delivery systems have the possibility/potential to modify their surface properties with fu...
