Extracellular vesicles (EVs) are a heterogeneous population of secreted membrane vesicles, with distinct biogenesis routes, biophysical properties and different functions both in physiological ...conditions and in disease. The release of EVs is a widespread biological process, which is conserved across species. In recent years, numerous studies have demonstrated that several bioactive molecules are trafficked with(in) EVs, such as microRNAs, mRNAs, proteins and lipids. The understanding of their final impact on the biology of specific target cells remains matter of intense debate in the field. Also, EVs have attracted great interest as potential novel cell-free therapeutics. Here we describe the proposed physiological and pathological functions of EVs, with a particular focus on their molecular content. Also, we discuss the advances in the knowledge of the mechanisms regulating the secretion of EV-associated molecules and the specific pathways activated upon interaction with the target cell, highlighting the role of EVs in the context of the immune system and as mediators of the intercellular signalling in the brain.
Ischemic stroke continues to be a leading cause of morbidity and mortality throughout the world. To protect and/or repair the ischemic brain, a multitiered approach may be centered on neural stem ...cell (NSC) transplantation. Transplanted NSCs exert beneficial effects not only via structural replacement, but also via immunomodulatory and/or neurotrophic actions. Unfortunately, the clinical translation of such promising therapies remains elusive, in part due to their limited persistence/survivability within the hostile ischemic microenvironment. Herein, we discuss current approaches for the development of NSCs more amenable to survival within the ischemic brain as a tool for future cellular therapies in stroke.
Spinal tuberculosis is due to globalization no longer a disease limited to developing nations. It remains in Germany a rarity and still a difficult diagnosis. Here we analyzed patients with spinal ...tuberculosis treated at our neurosurgical department. According to the infected anatomic segment, patients were assigned in one of three groups. Surgery was performed when neurological deficit due to mechanical compression, deformity, instability, severe pain, necrotic bone or failure to respond to anti-tuberculous treatment were observed. We identified 34 patients with spinal tuberculosis who underwent surgical treatment. In the cervical spinal tuberculosis group, there were 15 cases (46.9%) In most cases treatment consisted of spinal instrumentation. In the thoracic group, 10 cases (29.4%) were observed. The treatment was performed by dorsolateral spinal instrumentation. For the thoracolumbar group, 9 cases (26.4%) were observed. In most cases dorsolateral spinal instrumentation was performed. One patient in the first group and one patient in the third group relapsed after operation. A second surgery was necessary. Patients with chronic back pain, immigration background and/or neurological deficit spinal TB should be considered as a differential diagnosis. Combined surgical intervention and medical treatment is associated with a favorable outcome.
Oncolytic virotherapy is a rapidly progressing field that uses oncolytic viruses (OVs) to selectively infect malignant cells and cause an antitumor response through direct oncolysis and stimulation ...of the immune system. Despite demonstrated pre-clinical efficacy of OVs in many cancer types and some favorable clinical results in glioblastoma (GBM) trials, durable increases in overall survival have remained elusive. Recent evidence has emerged that tumor-associated macrophage/microglia (TAM) involvement is likely an important factor contributing to OV treatment failure. It is prudent to note that the relationship between TAMs and OV therapy failures is complex. Canonically activated TAMs (i.e., M1) drive an antitumor response while also inhibiting OV replication and spread. Meanwhile, M2 activated TAMs facilitate an immunosuppressive microenvironment thereby indirectly promoting tumor growth. In this focused review, we discuss the complicated interplay between TAMs and OV therapies in GBM. We review past studies that aimed to maximize effectiveness through immune system modulation-both immunostimulatory and immunosuppressant-and suggest future directions to maximize OV efficacy.
Background: The oral bioavailability of curcuminoids is low, but can be enhanced by incorporation into micelles. The major curcuminoid curcumin has antitumor effects on glioblastoma cells in vitro ...and in vivo. We therefore aimed to determine intratumoral concentrations and the clinical tolerance of highly bioavailable micellar curcuminoids in glioblastoma patients. Methods: Thirteen glioblastoma patients ingested 70 mg micellar curcuminoids 57.4 mg curcumin, 11.2 mg demethoxycurcumin (DMC), and 1.4 mg bis-demethoxycurcumin (BDMC) three times per day for 4 days (total amount of 689 mg curcumin, 134 mg DMC, and 17 mg BDMC) prior to planned resection of their respective brain tumors. Tumor and blood samples were taken during the surgery and analyzed for total curcuminoid concentrations.
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P magnetic resonance spectroscopic imaging was performed before and after curcuminoid consumption. Results: Ten patients completed the study. The mean intratumoral concentration of curcumin was 56 pg/mg of tissue (range 9-151), and the mean serum concentration was 253 ng/ml (range 129-364). Inorganic phosphate was significantly increased within the tumor (P = 0.034). The mean ratio of phosphocreatine to inorganic phosphate decreased, and the mean intratumoral pH increased (P = 0.08) after curcuminoid intervention. Conclusion: Oral treatment with micellar curcuminoids led to quantifiable concentrations of total curcuminoids in glioblastomas and may alter intratumoral energy metabolism.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Protein SUMOylation is a dynamic post-translational modification shown to be involved in a diverse set of physiologic processes throughout the cell. SUMOylation has also been shown to play a role in ...the pathobiology of myriad cancers, one of which is glioblastoma multiforme (GBM). As such, the clinical significance and therapeutic utility offered via the selective control of global SUMOylation is readily apparent. There are, however, relatively few known/effective inhibitors of global SUMO-conjugation. Herein we describe the identification of topotecan as a novel inhibitor of global SUMOylation. We also provide evidence that inhibition of SUMOylation by topotecan is associated with reduced levels of CDK6 and HIF-1α, as well as pronounced changes in cell cycle progression and cellular metabolism, thereby highlighting its putative role as an adjuvant therapy in defined GBM patient populations.
Diffuse midline gliomas (DMG) are a highly aggressive and universally fatal subgroup of pediatric tumors responsible for the majority of childhood brain tumor deaths. Median overall survival is less ...than 12 months with a 90% mortality rate at 2 years from diagnosis. Research into the underlying tumor biology and numerous clinical trials have done little to change the invariably poor prognosis. Continued development of novel, efficacious therapeutic options for DMGs remains a critically important area of active investigation. Given that DMGs are not amenable to surgical resection, have only limited response to radiation, and are refractory to traditional chemotherapy, immunotherapy has emerged as a promising alternative treatment modality. This review summarizes the various immunotherapy-based treatments for DMG as well as their specific limitations. We explore the use of cell-based therapies, oncolytic virotherapy or immunovirotherapy, immune checkpoint inhibition, and immunomodulatory vaccination strategies, and highlight the recent clinical success of anti-GD2 CAR-T therapy in diffuse intrinsic pontine glioma (DIPG) patients. Finally, we address the challenges faced in translating preclinical and early phase clinical trial data into effective standardized treatment for DMG patients.
The emerging field of cancer neuroscience reshapes our understanding of the intricate relationship between the nervous system and cancer biology; this new paradigm is likely to fundamentally change ...and advance neuro-oncological care. The profound interplay between cancers and the nervous system is reciprocal: Cancer growth can be induced and regulated by the nervous system; conversely, tumors can themselves alter the nervous system. Such crosstalk between cancer cells and the nervous system is evident in both the peripheral and central nervous systems. Recent advances have uncovered numerous direct neuron-cancer interactions at glioma-neuronal synapses, paracrine mechanisms within the tumor microenvironment, and indirect neuroimmune interactions. Neurosurgeons have historically played a central role in neuro-oncological care, and as the field of cancer neuroscience is becoming increasingly established, the role of neurosurgical intervention is becoming clearer. Examples include peripheral denervation procedures, delineation of neuron-glioma networks, development of neuroprostheses, neuromodulatory procedures, and advanced local delivery systems. The present review seeks to highlight key cancer neuroscience mechanisms with neurosurgical implications and outline the future role of neurosurgical intervention in cancer neuroscience.
Artificial intelligence (AI) has accelerated novel discoveries across multiple disciplines including medicine. Clinical medicine suffers from a lack of AI-based applications, potentially due to lack ...of awareness of AI methodology. Future collaboration between computer scientists and clinicians is critical to maximize the benefits of transformative technology in this field for patients. To illustrate, we describe AI-based advances in the diagnosis and management of gliomas, the most common primary central nervous system (CNS) malignancy.
Presented is a succinct description of foundational concepts of AI approaches and their relevance to clinical medicine, geared toward clinicians without computer science backgrounds. We also review novel AI approaches in the diagnosis and management of glioma.
Novel AI approaches in gliomas have been developed to predict the grading and genomics from imaging, automate the diagnosis from histopathology, and provide insight into prognosis.
Novel AI approaches offer acceptable performance in gliomas. Further investigation is necessary to improve the methodology and determine the full clinical utility of these novel approaches.
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