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Journal of Neurovirology Jun 2024The cellular prion protein (PrP) is an extracellular cell membrane protein. Due to its diversified roles, a definite role of PrP has been difficult to establish. During...
The cellular prion protein (PrP) is an extracellular cell membrane protein. Due to its diversified roles, a definite role of PrP has been difficult to establish. During viral infection, PrP has been reported to play a pleiotropic role. Here, we have attempted to envision the function of PrP in the neurotropic m-CoV-MHV-RSA59-induced model of neuroinflammation in C57BL/6 mice. A significant upregulation of PrP at protein and mRNA levels was evident in infected mouse brains during the acute phase of neuroinflammation. Furthermore, investigation of the effect of MHV-RSA59 infection on PrP expression in specific neuronal, microglial, and astrocytoma cell lines, revealed a differential expression of prion protein during neuroinflammation. Additionally, siRNA-mediated downregulation of prnp transcripts reduced the expression of viral antigen and viral infectivity in these cell lines. Cumulatively, our results suggest that PrP expression significantly increases during acute MHV-RSA59 infection and that PrP also assists in viral infectivity and viral replication.
PubMed: 38922550
DOI: 10.1007/s13365-024-01215-w -
Cells Jun 2024The world of cancer treatment is evolving rapidly and has improved the prospects of many cancer patients. Yet, there are still many cancers where treatment prospects... (Review)
Review
The world of cancer treatment is evolving rapidly and has improved the prospects of many cancer patients. Yet, there are still many cancers where treatment prospects have not (or hardly) improved. Glioblastoma is the most common malignant primary brain tumor, and even though it is sensitive to many chemotherapeutics when tested under laboratory conditions, its clinical prospects are still very poor. The blood-brain barrier (BBB) is considered at least partly responsible for the high failure rate of many promising treatment strategies. We describe the workings of the BBB during healthy conditions and within the glioblastoma environment. How the BBB acts as a barrier for therapeutic options is described as well as various approaches developed and tested for passing or opening the BBB, with the ultimate aim to allow access to brain tumors and improve patient perspectives.
Topics: Glioblastoma; Humans; Blood-Brain Barrier; Drug Delivery Systems; Brain Neoplasms; Antineoplastic Agents; Animals
PubMed: 38920629
DOI: 10.3390/cells13120998 -
Neurosurgery Jun 2024Isocitrate dehydrogenase (IDH)-mutant astrocytomas central nervous system World Health Organization grade 2 and 3 show heterogeneous appearance on MRI. In the...
The T1/T2 Ratio is Associated With Resectability in Patients With Isocitrate Dehydrogenase-Mutant Astrocytomas Central Nervous System World Health Organization Grades 2 and 3.
BACKGROUND AND OBJECTIVES
Isocitrate dehydrogenase (IDH)-mutant astrocytomas central nervous system World Health Organization grade 2 and 3 show heterogeneous appearance on MRI. In the premolecular era, the discrepancy between T1 hypointense and T2 hyperintense tumor volume in absolute values has been proposed as a marker for diffuse tumor growth. We set out to investigate if a ratio of T1 to T2 tumor volume (T1/T2 ratio) is associated with resectability and overall survival (OS) in patients with IDH-mutant astrocytomas.
METHODS
Patient data from 2 centers (Sahlgrenska University Hospital, Center A; LMU University Hospital, Center B) were collected retrospectively. Inclusion criteria were as follows: pre and postoperative MRI scans available for volumetric analysis (I), diagnosis of an IDH-mutant astrocytoma between 2003 and 2021 (II), and tumor resection at initial diagnosis (III). Tumor volumes were manually segmented. The T1/T2 ratio was calculated and correlated with extent of resection, residual T2 tumor volume, and OS.
RESULTS
The study comprised 134 patients with 65 patients included from Center A and 69 patients from Center B. The median OS was 134 months and did not differ between the cohorts (P = .29). Overall, the median T1/T2 ratio was 0.79 (range 0.15-1.0). Tumors displaying a T1/T2 ratio of 0.33 or lower showed significantly larger residual tumor volumes postoperatively (median 17.9 cm3 vs 4.6 cm3, P = .03). The median extent of resection in these patients was 65% vs 90% (P = .03). The ratio itself did not correlate with OS. In multivariable analyses, larger postoperative tumor volumes were associated with shorter survival times (hazard ratio 1.02, 95% CI 1.01-1.03, P < .01).
CONCLUSION
The T1/T2 ratio might be a good indicator for diffuse tumor growth on MRI and is associated with resectability in patients with IDH-mutant astrocytoma. This ratio might aid to identify patients in which an oncologically relevant tumor volume reduction cannot be safely achieved.
PubMed: 38920377
DOI: 10.1227/neu.0000000000003069 -
Frontiers in Oncology 2024Glioma is the most common primary intracranial neoplasm with a relatively poor prognosis.
INTRODUCTION
Glioma is the most common primary intracranial neoplasm with a relatively poor prognosis.
CASE PRESENTATION
Here, we present a unique case of a 53-year-old woman with two histopathologically distinct gliomas at the initial diagnosis. She presented with headaches and left limb weakness before admission, and magnetic resonance imaging (MRI) showed right frontal and basal ganglia area involvement combined with hemorrhage. The patient underwent a navigation-guided craniotomy for tumor removal. Pathological examination revealed the right frontal lobe lesion as a WHO grade II IDH-NOS astrocytoma, but the right parietal lobe lesion was a WHO grade IV IDH-mutant diffuse astrocytoma. Molecular detection of the parietal lesion revealed a point mutation at the R132 locus of the gene, no mutation in the promoter, amplification of the epidermal growth factor receptor, and a non-homozygous deletion.
DISCUSSION
In-depth epigenomic analysis and molecular examination revealed that one patient had two different brain tumors, underscoring the importance of performing a comprehensive brain tumor workup.
CONCLUSION
This unique case confirms that adjacent astrocytomas may have different molecular pathogenesis and provides novel insights into the development of gliomas.
PubMed: 38919539
DOI: 10.3389/fonc.2024.1308497 -
Medical Oncology (Northwood, London,... Jun 2024Glioblastoma (GBM) is the most common malignant brain tumor, which, despite significant progress made in the last years in the field of neuro-oncology, remains an... (Review)
Review
Glioblastoma (GBM) is the most common malignant brain tumor, which, despite significant progress made in the last years in the field of neuro-oncology, remains an incurable disease. GBM has a poor prognosis with a median survival of 12-15 months, and its aggressive clinical course is related to rapid growth, extensive infiltration of adjacent tissues, resistance to chemotherapy, radiotherapy and immunotherapy, and frequent relapse. Currently, several molecular biomarkers are used in clinical practice to predict patient prognosis and response to treatment. However, due to the overall unsatisfactory efficacy of standard multimodal treatment and the remaining poor prognosis, there is an urgent need for new biomarkers and therapeutic strategies for GBM. Recent evidence suggests that GBM tumorigenesis is associated with crosstalk between cancer, immune and stromal cells mediated by various cytokines. One of the key factors involved in this process appears to be interleukin-17 (IL-17), a pro-inflammatory cytokine that is significantly upregulated in the serum and tissue of GBM patients. IL-17 plays a key role in tumorigenesis, angiogenesis, and recurrence of GBM by activating pro-oncogenic signaling pathways and promoting cell survival, proliferation, and invasion. IL-17 facilitates the immunomodulation of the tumor microenvironment by promoting immune cells infiltration and cytokine secretion. In this article we review the latest scientific reports to provide an update on the role of IL-17 role in tumorigenesis, tumor microenvironment, diagnosis, prognosis, and treatment of GBM.
Topics: Humans; Glioblastoma; Brain Neoplasms; Interleukin-17; Tumor Microenvironment; Biomarkers, Tumor; Prognosis
PubMed: 38918274
DOI: 10.1007/s12032-024-02434-1 -
Frontiers in Immunology 2024Glioblastoma (GBM) is a highly malignant, invasive, and poorly prognosed brain tumor. Unfortunately, active comprehensive treatment does not significantly prolong... (Review)
Review
Glioblastoma (GBM) is a highly malignant, invasive, and poorly prognosed brain tumor. Unfortunately, active comprehensive treatment does not significantly prolong patient survival. With the deepening of research, it has been found that gut microbiota plays a certain role in GBM, and can directly or indirectly affect the efficacy of immune checkpoint inhibitors (ICIs) in various ways. (1) The metabolites produced by gut microbiota directly affect the host's immune homeostasis, and these metabolites can affect the function and distribution of immune cells, promote or inhibit inflammatory responses, affect the phenotype, angiogenesis, inflammatory response, and immune cell infiltration of GBM cells, thereby affecting the effectiveness of ICIs. (2) Some members of the gut microbiota may reverse T cell function inhibition, increase T cell anti-tumor activity, and ultimately improve the efficacy of ICIs by targeting specific immunosuppressive metabolites and cytokines. (3) Some members of the gut microbiota directly participate in the metabolic process of drugs, which can degrade, transform, or produce metabolites, affecting the effective concentration and bioavailability of drugs. Optimizing the structure of the gut microbiota may help improve the efficacy of ICIs. (4) The gut microbiota can also regulate immune cell function and inflammatory status in the brain through gut brain axis communication, indirectly affecting the progression of GBM and the therapeutic response to ICIs. (5) Given the importance of gut microbiota for ICI therapy, researchers have begun exploring the use of fecal microbiota transplantation (FMT) to transplant healthy or optimized gut microbiota to GBM patients, in order to improve their immune status and enhance their response to ICI therapy. Preliminary studies suggest that FMT may enhance the efficacy of ICI therapy in some patients. In summary, gut microbiota plays a crucial role in regulating ICIs in GBM, and with a deeper understanding of the relationship between gut microbiota and tumor immunity, it is expected to develop more precise and effective personalized ICI therapy strategies for GBM, in order to improve patient prognosis.
Topics: Humans; Gastrointestinal Microbiome; Glioblastoma; Immune Checkpoint Inhibitors; Brain Neoplasms; Animals; Brain-Gut Axis; Fecal Microbiota Transplantation; Tumor Microenvironment
PubMed: 38915399
DOI: 10.3389/fimmu.2024.1401967 -
Frontiers in Microbiology 2024Herpes Simplex Virus type 1 (HSV-1) 1 is a neurotropic virus that has been associated with neurodegenerative disorders. The dysregulation of autophagy by HSV-1 has been...
Herpes Simplex Virus type 1 (HSV-1) 1 is a neurotropic virus that has been associated with neurodegenerative disorders. The dysregulation of autophagy by HSV-1 has been proposed as a potential cause of neurodegeneration. While studies have extensively tackled the interaction between autophagy and HSV-1 in neurons, research in glial cells is currently limited. Our studies demonstrate that HSV-1 inhibits, but not completely blocks, the formation of autophagosomes in human oligodendroglioma- and astrocytoma- derived cell lines. These findings have been confirmed in murine oligodendrocyte precursor cells (OPCs). Finally, this study investigates the impact of autophagy on HSV-1 infection in glial cells. While the lack of basal autophagy in LC3B knockout glial cells does not have a significant effect on viral infection, cells without the autophagy-related protein ATG5 exhibit reduced viral production. The absence of ATG5 leads to a decrease in the transcription and replication of viral genes, as well as a delay in the initial stages of the formation of HSV-1 replication compartments. These findings indicate that while autophagy may not play a significant role in antiviral defense in glial cells, HSV-1 may be inhibiting autophagy to exploit non-canonical functions of certain components of the autophagic machinery, such as ATG5, to benefit its lifecycle.
PubMed: 38915300
DOI: 10.3389/fmicb.2024.1411655 -
Scientific Data Jun 2024Hyperspectral (HS) imaging (HSI) technology combines the main features of two existing technologies: imaging and spectroscopy. This allows to analyse simultaneously the...
Hyperspectral (HS) imaging (HSI) technology combines the main features of two existing technologies: imaging and spectroscopy. This allows to analyse simultaneously the morphological and chemical attributes of the objects captured by a HS camera. In recent years, the use of HSI provides valuable insights into the interaction between light and biological tissues, and makes it possible to detect patterns, cells, or biomarkers, thus, being able to identify diseases. This work presents the HistologyHSI-GB dataset, which contains 469 HS images from 13 patients diagnosed with brain tumours, specifically glioblastoma. The slides were stained with haematoxylin and eosin (H&E) and captured using a microscope at 20× power magnification. Skilled histopathologists diagnosed the slides and provided image-level annotations. The dataset was acquired using custom HSI instrumentation, consisting of a microscope equipped with an HS camera covering the spectral range from 400 to 1000 nm.
Topics: Humans; Glioblastoma; Brain Neoplasms; Hyperspectral Imaging; Microscopy
PubMed: 38914542
DOI: 10.1038/s41597-024-03510-x -
AJNR. American Journal of Neuroradiology Jun 2024Hemangioblastoma is a rare vascular tumor that occurs within the central nervous system in children. Differentiating hemangioblastoma from other posterior fossa tumors...
BACKGROUND AND PURPOSE
Hemangioblastoma is a rare vascular tumor that occurs within the central nervous system in children. Differentiating hemangioblastoma from other posterior fossa tumors can be challenging on imaging, and preoperative diagnosis can change the neurosurgical approach. We hypothesize that a 'lightbulb sign' on the ASL sequence (diffuse homogenous intense hyperperfusion within the solid component of the tumor) will provide additional imaging finding to differentiate hemangioblastoma from other posterior fossa tumors.
MATERIALS AND METHODS
In this retrospective comparative observational study, we only included pathology-proven cases of hemangioblastoma, while the control group consisted of other randomly selected pathology-proven posterior fossa tumors from January 2022 to January 2024. Two blinded neuroradiologists analyzed all applicable MRI sequences, including ASL sequence if available. ASL was analyzed for the 'lightbulb sign'. Disagreements between the radiologists were resolved by a third pediatric neuroradiologist. Chi-square and Fisher's exact test were used to analyze the data.
RESULTS
95 patients were enrolled in the study; 57 (60%) were male. The median age at diagnosis was 8 years old (IQR: 3-14). Out of the enrolled patients, 8 had hemangioblastoma, and 87 had other posterior fossa tumors, including medulloblastoma (n=31), pilocytic astrocytoma (n=23), posterior fossa ependymoma type A (n=16), and other tumors (n=17). The comparison of hemangioblastoma vs non-hemangioblastoma showed that peripheral edema (p=0.02) and T2 flow void (p=0.02) favors hemangioblastoma, whereas reduced diffusion (low ADC) (p=0.002) and ventricular system extension (p=0.001) favors nonhemangioblastoma tumors.Forty-two cases also had ASL perfusion sequences. While high perfusion favors hemangioblastoma (p=0.03), the lightbulb sign shows a complete distinction since all the ASL series of hemangioblastoma cases (n=4) showed the lightbulb sign, whereas none of the nonhemangioblastoma cases (n=38) showed the sign (p<0.001).
CONCLUSIONS
Lightbulb-like intense and homogenous hyperperfusion patterns on ASL are helpful in diagnosing posterior fossa hemangioblastoma in children.ABBREVIATIONS ASL = Arterial spin labelling; pASL = Pulsed arterial spin labelling; pCASL = Pseudocontinuous arterial spin labelling; DCE = Dynamic contrast-enhanced; DSC = Dynamic susceptibility contrast; VHL = Von Hippel Lindau.
PubMed: 38914433
DOI: 10.3174/ajnr.A8391 -
Neuro-oncology Jun 2024The 2016 and 2021 World Health Organization (WHO) 2021 Classification of Central Nervous System (CNS) tumors have resulted in a major improvement of the classification...
The biological significance of tumor grade, age, enhancement and extent of resection in IDH mutant gliomas: how should they inform treatment decision in the era of IDH inhibitors? Invited review.
The 2016 and 2021 World Health Organization (WHO) 2021 Classification of Central Nervous System (CNS) tumors have resulted in a major improvement of the classification of IDH-mutant gliomas. With more effective treatments many patients experience prolonged survival . However, treatment guidelines are often still based on information from historical series comprising both patients with IDHwt and IDH mutant tumors. They provide recommendations for radiotherapy and chemotherapy for so-called high-risk patients, usually based on residual tumor after surgery and age over 40. More up-to-date studies give a better insight into clinical, radiological and molecular factors associated with outcome of patients with IDH-mutant glioma. These insights should be used today for risk stratification and for treatment decisions. In many patients with an IDH-mutant grade 2 and grade 3 glioma, if carefully monitored postponing radiotherapy and chemotherapy is safe, and will not jeopardize overall outcome of patients. With the INDIGO trial showing patient benefit from the IDH inhibitor vorasidenib, there is a sizable population in which it seems reasonable to try this class of agents before recommending radio-chemotherapy with its delayed adverse event profile affecting quality of survival. Ongoing trials should help to further identify the patients that are benefiting from this treatment.
PubMed: 38912846
DOI: 10.1093/neuonc/noae107