scholarly journals The Presence and Potential Role of ALDH1A2 in the Glioblastoma Microenvironment

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2485
Author(s):  
Stephanie Sanders ◽  
Denise M. Herpai ◽  
Analiz Rodriguez ◽  
Yue Huang ◽  
Jeff Chou ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Potential Role ◽  
Therapeutic Agents ◽  
Brain Parenchyma ◽  
Low Grade ◽  
Effective Management ◽  
Diffuse Infiltration ◽  
Protein Levels ◽  
The Brain

Glioblastoma (GBM) is the most aggressive malignant glioma. Therapeutic targeting of GBM is made more difficult due to its heterogeneity, resistance to treatment, and diffuse infiltration into the brain parenchyma. Better understanding of the tumor microenvironment should aid in finding more effective management of GBM. GBM-associated macrophages (GAM) comprise up to 30% of the GBM microenvironment. Therefore, exploration of GAM activity/function and their specific markers are important for developing new therapeutic agents. In this study, we identified and evaluated the expression of ALDH1A2 in the GBM microenvironment, and especially in M2 GAM, though it is also expressed in reactive astrocytes and multinucleated tumor cells. We demonstrated that M2 GAM highly express ALDH1A2 when compared to other ALDH1 family proteins. Additionally, GBM samples showed higher expression of ALDH1A2 when compared to low-grade gliomas (LGG), and this expression was increased upon tumor recurrence both at the gene and protein levels. We demonstrated that the enzymatic product of ALDH1A2, retinoic acid (RA), modulated the expression and activity of MMP-2 and MMP-9 in macrophages, but not in GBM tumor cells. Thus, the expression of ALDH1A2 may promote the progressive phenotype of GBM.

Amiloride-sensitive Na+ channels contribute to regulatory volume increases in human glioma cells

2007 ◽  
Vol 293 (3) ◽  
pp. C1181-C1185 ◽  
Author(s):  
Sandra B. Ross ◽  
Catherine M. Fuller ◽  
James K. Bubien ◽  
Dale J. Benos
Keyword(s):  
Ion Channel ◽  
Potential Role ◽  
Glioma Cells ◽  
Brain Parenchyma ◽  
Volume Increase ◽  
Cation Conductance ◽  
Normal Human ◽  
Hyperosmolar Solutions ◽  
The Brain

Despite intensive research, brain tumors remain among the most difficult type of malignancies to treat, due largely to their diffusely invasive nature and the associated difficulty of adequate surgical resection. To migrate through the brain parenchyma and to proliferate, glioma cells must be capable of significant changes in shape and volume. We have previously reported that glioma cells express an amiloride- and psalmotoxin-sensitive cation conductance that is not found in normal human astrocytes. In the present study, we investigated the potential role of this ion channel to mediate regulatory volume increase in glioma cells. We found that the ability of the cells to volume regulate subsequent to cell shrinkage by hyperosmolar solutions was abolished by both amiloride and psalmotoxin 1. This toxin is thought to be a specific peptide inhibitor of acid-sensing ion channel (ASIC1), a member of the Deg/ENaC superfamily of cation channels. We have previously shown this toxin to be an effective blocker of the glioma cation conductance. Our data suggest that one potential role for this conductance may be to restore cell volume during the cell's progression thorough the cell cycle and while the tumor cell migrates within the interstices of the brain.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

scholarly journals Macrophages and microglia: the cerberus of glioblastoma

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Alice Buonfiglioli ◽  
Dolores Hambardzumyan
Keyword(s):  
Tumor Cells ◽  
Innate Immune System ◽  
Tumor Heterogeneity ◽  
Expression Profiles ◽  
Brain Parenchyma ◽  
Innate Immune ◽  
Malignant Growth ◽  
Neoplastic Cells ◽  
Functional Roles ◽  
The Brain

AbstractGlioblastoma (GBM) is the most aggressive and deadliest of the primary brain tumors, characterized by malignant growth, invasion into the brain parenchyma, and resistance to therapy. GBM is a heterogeneous disease characterized by high degrees of both inter- and intra-tumor heterogeneity. Another layer of complexity arises from the unique brain microenvironment in which GBM develops and grows. The GBM microenvironment consists of neoplastic and non-neoplastic cells. The most abundant non-neoplastic cells are those of the innate immune system, called tumor-associated macrophages (TAMs). TAMs constitute up to 40% of the tumor mass and consist of both brain-resident microglia and bone marrow-derived myeloid cells from the periphery. Although genetically stable, TAMs can change their expression profiles based upon the signals that they receive from tumor cells; therefore, heterogeneity in GBM creates heterogeneity in TAMs. By interacting with tumor cells and with the other non-neoplastic cells in the tumor microenvironment, TAMs promote tumor progression. Here, we review the origin, heterogeneity, and functional roles of TAMs. In addition, we discuss the prospects of therapeutically targeting TAMs alone or in combination with standard or newly-emerging GBM targeting therapies.

scholarly journals Primary Cranial Vault Lymphoma Extending between Subcutaneous Tissue and Brain Parenchyma without Skull Destruction after Mild Head Trauma: A Case Report and Literature Review

2021 ◽  
pp. 1118-1123
Author(s):  
Kengo Setta ◽  
Takaaki Beppu ◽  
Yuichi Sato ◽  
Hiroaki Saura ◽  
Junichi Nomura ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Head Trauma ◽  
Dura Mater ◽  
Subcutaneous Tissue ◽  
Bone Destruction ◽  
B Cell Lymphoma ◽  
Brain Parenchyma ◽  
Skin Tumor ◽  
Cranial Vault ◽  
The Brain

Malignant lymphoma of the head rarely arises outside of the brain parenchyma as primary cranial vault lymphoma (PCVL). A case of PCVL that invaded from subcutaneous tissue into the brain, passing through the skull, and occurred after mild head trauma is reported along with a review of the literature. The patient was a 75-year-old man with decreased activity. One month before his visit to our hospital, he bruised the left frontal area of his head. Magnetic resonance imaging showed homogeneously enhanced tumors with contrast media in the subcutaneous tissue corresponding to the head impact area and the cerebral parenchyma, but no obvious abnormal findings in the skull. A biopsy with craniotomy was performed under general anesthesia. The pathological diagnosis was diffuse large B-cell lymphoma. On histological examination, tumor cells grew aggressively under the skin. Tumor cells invaded along the emissary vein into the external table without remarkable bone destruction and extended across the skull through the Haversian canals in the diploe. Tumor cells were found only at the perivascular areas in the dura mater and extended into the brain parenchyma. Considering the history of head trauma and the neuroimaging and histological findings, the PCVL in the present case arose primarily under the skin, passed though the skull and dura mater, and invaded along vessels and reached the brain.

PREY PREFERENCES OF ADULT AND IMMATURE ZETZELLIA MALI EWING (ACARI: STIGMAEIDAE) AND TYPHLODROMUS CAUDIGLANS SCHUSTER (ACARI: PHYTOSEIIDAE)

1993 ◽  
Vol 125 (5) ◽  
pp. 967-969 ◽  
Author(s):  
David R. Clements ◽  
Rudolf Harmsen
Keyword(s):  
Biological Control ◽  
Potential Role ◽  
Panonychus Ulmi ◽  
Economic Damage ◽  
Apple Orchards ◽  
Effective Management ◽  
Phytoseiid Mites ◽  
Prey Preferences ◽  
Eriophyid Mites

Effective management of the interactions within the mite community is critical to biological control of economically damaging phytophagous mites such as Panonychus ulmi Koch (Tetranychidae) (Clements and Harmsen 1990). Although much is known about the potential role of phytoseiid mites in controlling P. ulmi (Dover et al. 1979), mites from at least seven other families may be present in apple orchards (Thistlewood 1991). Stigmaeid mites are predators which may play a beneficial role in biological control in conjunction with phytoseiids (Clements and Harmsen 1992). Eriophyid mites are phytophagous but seldom cause economic damage, and may compete with tetranychids and provide alternative food for predators of tetranychids (Croft and Hoying 1977).

Role of susceptibility weighted imaging (SWI) in assessment of intra axial brain neoplasms in adults

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Pasant Mohamed Abo-Elhoda Darwish Mohamed Abo-Elhoda ◽  
Hesham Mahmoud Ahmed Mansour ◽  
Yosra Abdelzaher Abdullah ◽  
Eman Ahmed Fouad Darwish
Keyword(s):  
Brain Neoplasms ◽  
Tumor Size ◽  
Venous Blood ◽  
Brain Parenchyma ◽  
P Value ◽  
Susceptibility Weighted Imaging ◽  
Low Grade ◽  
Chi Square ◽  
Cross Sectional

Abstract Background Susceptibility weighted imaging (SWI) is a 3D gradient-echo MR technique that is based on blood oxygen level dependent (BOLD) induced phase effects between the venous blood and the surrounding brain parenchyma. SW-MR imaging allows for noninvasive visualization of small veins at submillimeter resolution and, therefore, is used to depict venous architecture in brain lesions. The extreme sensitivity of SWI for the detection of neovascularity (venous blood), haemorrhage, and calcification has been an indispensable tool for characterization of the internal architecture of brain tumours. Objectives Is to evaluate the role of Susceptibility weighted imaging in assessment of adults Intra axial brain Neoplasms, and its ability to characterize them into high and low grade lesions in comparison to histopathology which will be used as gold standard. Methods A cross sectional study including 31 patients suspecting intracranial brain neoplasm radiologically and clinically, conducted at Private center, the patients were investigated using Siemens machine Magnetom Skyra 3T, the period was between January 2018 till the end of June 2019 . Results Our study included 31 patients. Including 15 female and 16 male patients, with the patient’s age ranging from 20 to 68 years old with median 48 years old ranging from 35.75 (25% percentile) to 58.75 (75% percentile). Among total cases, there were 8 patients with grade 2 glioma, 10 patients with grade 3 glioma and 6 patients with grade 4 glioma, 2 patients with lymphoma and 5 patients with brain metastasis (1 lung cancer and 4 breast cancer). All the patients were evaluated with MRI including SWI sequence with special comment on the number of the intratumoral susceptibility signal (ITSS), the size of the ITSS, its morphology as well as the ratio of the ITSS to the tumor size, which were then correlated with the patient histopathological results obtained later. The study revealed that the best parameter to accurately grade the tumor is the number of ITSS within the lesion with P value 0.001, followed by the size of the ITSS with P value 0.002 and Pearson Chi-Square value equals 20.6, while the lowest one was the ratio of the ITSS to the tumor size with P value 0.002 Pearson Chi-Square value equals 17.3. Our study showed that the morphology alone was not able to accurately grade the tumor with P value 0.007 ( Not significant) Conclusion SWI using 3T MR system provides quite useful information for preoperative tumor grading. There seems to be a strong correlation between pathological grading and that assessed with SWI.

scholarly journals PPAR Gamma and Viral Infections of the Brain

2021 ◽  
Vol 22 (16) ◽  
pp. 8876
Author(s):  
Pierre Layrolle ◽  
Pierre Payoux ◽  
Stéphane Chavanas
Keyword(s):  
Viral Infections ◽  
Ppar Gamma ◽  
Brain Parenchyma ◽  
Peroxisome Proliferator ◽  
Neural Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Immunodeficiency Virus ◽  
Health And Disease ◽  
The Brain

Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a master regulator of metabolism, adipogenesis, inflammation and cell cycle, and it has been extensively studied in the brain in relation to inflammation or neurodegeneration. Little is known however about its role in viral infections of the brain parenchyma, although they represent the most frequent cause of encephalitis and are a major threat for the developing brain. Specific to viral infections is the ability to subvert signaling pathways of the host cell to ensure virus replication and spreading, as deleterious as the consequences may be for the host. In this respect, the pleiotropic role of PPARγ makes it a critical target of infection. This review aims to provide an update on the role of PPARγ in viral infections of the brain. Recent studies have highlighted the involvement of PPARγ in brain or neural cells infected by immunodeficiency virus 1, Zika virus, or human cytomegalovirus. They have provided a better understanding on PPARγ functions in the infected brain, and revealed that it can be a double-edged sword with respect to inflammation, viral replication, or neuronogenesis. They unraveled new roles of PPARγ in health and disease and could possibly help designing new therapeutic strategies.

scholarly journals The purine receptor P2X7R regulates the release of pro-inflammatory cytokines in human craniopharyngioma

2017 ◽  
Vol 24 (6) ◽  
pp. 287-296 ◽  
Author(s):  
Jing Nie ◽  
Guang-long Huang ◽  
Sheng-Ze Deng ◽  
Yun Bao ◽  
Ya-Wei Liu ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Inflammatory Cytokines ◽  
Tumor Tissue ◽  
Brain Parenchyma ◽  
Surrounding Tissue ◽  
Protein Levels ◽  
Cytokine Modulation ◽  
Selective Agonists ◽  
Cultured Tumor Cells ◽  
Pro Inflammatory Cytokines

Craniopharyngiomas (CPs) are usually benign, non-metastasizing embryonic malformations originating from the sellar area. They are, however, locally invasive and generate adherent interfaces with the surrounding brain parenchyma. Previous studies have shown the tumor microenvironment is characterized by a local abundance of adenosine triphosphate (ATP), infiltration of leukocytes and elevated levels of pro-inflammatory cytokines that are thought to be responsible, at least in part, for the local invasion. Here, we examine whether ATP, via the P2X7R, participates in the regulation of cytokine expression in CPs. The expression of P2X7R and pro-inflammatory cytokines were measured at the RNA and protein levels both in tumor samples and in primary cultured tumor cells. Furthermore, cytokine modulation was measured after manipulating P2X7R in cultured tumor cells by siRNA-mediated knockdown, as well as pharmacologically by using selective agonists and antagonists. The following results were observed. A number of cytokines, in particular IL-6, IL-8 and MCP-1, were elevated in patient plasma, tumor tissue and cultured tumor cells. P2X7R was expressed in tumor tissue as well as in cultured tumor cells. RNA expression as measured in 48 resected tumors was positively correlated with the RNA levels of IL-6, IL-8 and MCP-1 in tumors. Furthermore, knockdown of P2X7R in primary tumor cultures reduced, and stimulation of P2XR7 by a specific agonist enhanced the expression of these cytokines. This latter stimulation involved a Ca2+-dependent mechanism and could be counteracted by the addition of an antagonist. In conclusion, the results suggest that P2X7R may promote IL-6, IL-8 and MCP-1 production and secretion and contribute to the invasion and adhesion of CPs to the surrounding tissue.

Potential Role of Darvyadi Kwatha in the Management of Diabetes

The Healer ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 80-86
Author(s):  
Shankar Gautam ◽  
Abhishek Upadhyay ◽  
Rashmi Mutha ◽  
BINOD KUMAR SINGH ◽  
Ram Kishor Joshi
Keyword(s):  
Causes Of Death ◽  
Potential Role ◽  
Critical Role ◽  
Animal Experiments ◽  
Safety Evaluation ◽  
New Drugs ◽  
Effective Management ◽  
The Individual ◽  
Glucose 6 Phosphate Dehydrogenase

Diabetes is a clinical condition characterized by a spike in blood glucose in plasma. It is one of the 21st century's greatest public health crises and is among the top 10 causes of death worldwide. Although new drugs and therapeutics are emerging for its management but the prevalence is increasing at an alarming pace; thus, every system must contribute for effective management. An effort is made to review the efficacy and safety evaluation of the individual herbs of Darvyadi Kwatha (DK), an Ayurvedic formulation mentioned in Charaka Samhita. The constituents of the DK has some strong efficient antidiabetic/hypoglycaemic chemical principle having insulin-triggering and insulin-like behaviors which increases the activity of glucose-6-phosphate dehydrogenase (G6PD) and glucokinase and decreases glucose-6-phosphatase activity, reduce oxidative stress and prevention of glutathione reductase, superoxide dismutase, and catalase activity play a critical role in glucose homeostasis. DK also improve biochemical parameters such as SGPT, SGOT, cholesterol and triglycerides and is found to be safe in animal experiments. The various evidences clearly indicates that DK has definite hypoglycemic potential as well as anti-diabetic activity.

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