Estrogen α and ß Receptor Expression in the Various Regions of Resected Glioblastoma Multiforme Tumors and in an In Vitro Model.

Glioblastoma multiforme (GBM) is a malignant tumor with a higher prevalence in men and a higher survival rate in transmenopausal women. It exhibits distinct areas influenced by changing environmental conditions. This study examines how these areas differ in the levels of estrogen receptors (ERs) which play an important role in the development and progression of many cancers, and whose expression levels are often correlated with patient survival. This study utilized two research models: an in vitro model employing the U87 cell line and a second model involving tumors resected from patients (including tumor core, enhancing tumor region, and peritumoral area). ER expression was assessed at both gene and protein levels, with the results validated using confocal microscopy and immunohistochemistry. Under hypoxic conditions, the U87 line displayed a decrease in ERß mRNA expression and an increase in ERα mRNA expression. In patient samples, ERß mRNA expression was lower in the tumor core compared to the enhancing tumor region (only in males when the study group was divided by sex). In addition, ERß protein expression was lower in the tumor core than in the peritumoral area (only in women when the study group was divided by sex). Immunohistochemical analysis indicated the highest ERß protein expression in the enhancing tumor area, followed by the peritumoral area, and the lowest in the tumor core. The findings suggest that ER expression may significantly influence the development of GBM, exhibiting variability under the influence of conditions present in different tumor areas.

Reduced Expression of Very-Long-Chain Acyl-CoA Synthetases SLC27A4 and SLC27A6 in the Glioblastoma Tumor Compared to the Peritumoral Area.

This study aimed to analyze solute carrier family 27 (SLC27) in glioblastoma tumors. The investigation of these proteins will provide insight into how and to what extent fatty acids are taken up from the blood in glioblastoma tumors, as well as the subsequent fate of the up-taken fatty acids. Tumor samples were collected from a total of 28 patients and analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). The study also sought to explore the relationship between SLC27 expression and patient characteristics (age, height, weight, body mass index (BMI), and smoking history), as well as the expression levels of enzymes responsible for fatty acid synthesis. The expression of SLC27A4 and SLC27A6 was lower in glioblastoma tumors compared to the peritumoral area. Men had a lower expression of SLC27A5. Notably, a positive correlation was observed between the expression of SLC27A4, SLC27A5, and SLC27A6 and smoking history in women, whereas men exhibited a negative correlation between these SLC27s and BMI. The expression of SLC27A1 and SLC27A3 was positively correlated with the expression of ELOVL6. In comparison to healthy brain tissue, glioblastoma tumors take up fewer fatty acids. The metabolism of fatty acids in glioblastoma is dependent on factors such as obesity and smoking.

Androgen Receptor Expression in the Various Regions of Resected Glioblastoma Multiforme Tumors and in an In Vitro Model.

Glioblastoma multiforme (GBM) is a malignant glioma, difficult to detect and with the lowest survival rates among gliomas. Its greater incidence among men and its higher survival rate among premenopausal women suggest that it may be associated with the levels of androgens. As androgens stimulate the androgen receptor (AR), which acts as a transcription factor, the aim of this study was the investigate the role of AR in the progression of GBM. The study was conducted on tissues collected from three regions of GBM tumors (tumor core, enhancing tumor region, and peritumoral area). In addition, an in vitro experiment was conducted on U-87 cells under various culture conditions (necrotic, hypoxic, and nutrient-deficient), mimicking the conditions in a tumor. In both of the models, androgen receptor expression was determined at the gene and protein levels, and the results were confirmed by confocal microscopy and immunohistochemistry. AR mRNA expression was higher under nutrient-deficient conditions and lower under hypoxic conditions in vitro. However, there were no differences in AR protein expression. No differences in AR mRNA expression were observed between the tested tumor structures taken from patients. No differences in AR mRNA expression were observed between the men and women. However, AR protein expression in tumors resected from patients was higher in the enhancing tumor region and in the peritumoral area than in the tumor core. In women, higher AR expression was observed in the peritumoral area than in the tumor core. AR expression in GBM tumors did not differ significantly between men and women, which suggests that the higher incidence of GBM in men is not associated with AR expression. In the group consisting of men and women, AR expression varied between the regions of the tumor: AR expression was higher in the enhancing tumor region and in the peritumoral area than in the tumor core, showing a dependence on tumor conditions (hypoxia and insufficient nutrient supply).

Glioblastoma Multiforme Tumors in Women Have a Lower Expression of Fatty Acid Elongases ELOVL2, ELOVL5, ELOVL6, and ELOVL7 than in Men.

One line of research on the possible ways of inhibiting the growth of glioblastoma multiforme (GBM), a brain tumor with a very poor prognosis, is the analysis of its metabolism, such as fatty acid synthesis by desaturases and elongases. This study examines the expression of elongases ELOVL1, ELOVL2, ELOVL3, ELOVL4, ELOVL5, ELOVL6, and ELOVL7 in GBM tumor samples from 28 patients (16 men and 12 women), using a quantitative real-time polymerase chain reaction (qRT-PCR). To demonstrate the influence of the tumor microenvironment on the tested elongases, U-87 MG cells were cultured in nutrient-deficient conditions and with cobalt chloride (CoCl2) as a hypoxia-mimetic agent. The results showed that the expression of ELOVL1 and ELOVL7 in the GBM tumor was lower than in the peritumoral area. The expression of six of the seven studied elongases differed between the sexes. Hypoxia increased the expression of ELOVL5 and ELOVL6 and decreased the expression of ELOVL1, ELOVL3, ELOVL4, and ELOVL7 in U-87 MG cells. These results indicate that the synthesis of fatty acids, especially polyunsaturated fatty acids (PUFA), in GBM tumors may be higher in men than in women. In contrast, the synthesis of saturated fatty acids (SFA) may be higher in women than in men.

Expression of SCD and FADS2 Is Lower in the Necrotic Core and Growing Tumor Area than in the Peritumoral Area of Glioblastoma Multiforme.

The expression of desaturases is higher in many types of cancer, and despite their recognized role in oncogenesis, there has been no research on the expression of desaturases in glioblastoma multiforme (GBM). Tumor tissue samples were collected during surgery from 28 patients (16 men and 12 women) diagnosed with GBM. The effect of necrotic conditions and nutritional deficiency (mimicking conditions in the studied tumor zones) was studied in an in vitro culture of human brain (glioblastoma astrocytoma) U-87 MG cells. Analysis of desaturase expression was made by qRT-PCR and the immunohistochemistry method. In the tumor, the expression of stearoyl-coenzyme A desaturase (SCD) and fatty acid desaturases 2 (FADS2) was lower than in the peritumoral area. The expression of other desaturases did not differ in between the distinguished zones. We found no differences in the expression of SCD, fatty acid desaturases 1 (FADS1), or FADS2 between the sexes. Necrotic conditions and nutritional deficiency increased the expression of the studied desaturase in human brain (glioblastoma astrocytoma) U-87 MG cells. The obtained results suggest that (i) biosynthesis of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) in a GBM tumor is less intense than in the peritumoral area; (ii) expressions of SCD, SCD5, FADS1, and FADS2 correlate with each other in the necrotic core, growing tumor area, and peritumoral area; (iii) expressions of desaturases in a GBM tumor do not differ between the sexes; and (iv) nutritional deficiency increases the biosynthesis of MUFA and PUFA in GBM cells.

Morphine-element interactions - The influence of selected chemical elements on neural pathways associated with addiction.

Addiction is a pressing social problem worldwide and opioid dependence can be considered the strongest and most difficult addiction to treat. Mesolimbic and mesocortical dopaminergic pathways play an important role in modulation of cognitive processes and decision making and, therefore, changes in dopamine metabolism are considered the central basis for the development of dependence. Disturbances caused by excesses or deficiency of certain elements have a significant impact on the functioning of the central nervous system (CNS) both in physiological conditions and in pathology and can affect the cerebral reward system and therefore, may modulate processes associated with the development of addiction. In this paper we review the mechanisms of interactions between morphine and zinc, manganese, chromium, cadmium, lead, fluoride, their impact on neural pathways associated with addiction, and on antinociception and morphine tolerance and dependence.

Diagnostic value of non-enhanced computed tomography in identifying location of ruptured cerebral aneurysm in patients with aneurysmal subarachnoid haemorrhage.

BACKGROUND: In patients with SAH and multiple aneurysms, the ruptured lesion must be identified to prevent recurrent bleeding. AIM OF THE STUDY: To assess the diagnostic value of non-enhanced computed tomography (NECT) in identifying the rupture site in patients with subarachnoid haemorrhage (SAH) and multiple aneurysms. MATERIAL AND METHODS: We included patients with SAH revealed by NECT and multiple aneurysms detected on computed tomography angiography (CTA) in whom a ruptured aneurysm was identified during neurosurgery. Two radiologists predicted the location of the ruptured aneurysm based on the distribution of the SAH and location of intracerebral haematoma (ICH) by NECT. RESULTS: Eighty-three patients with a mean age of 55.7 ± 14.4 years were included. Ruptured aneurysms were significantly larger (mean size 7.7 ± 4.7 mm) than unruptured aneurysms (mean size 5.9 ± 4.5 mm; p = 0.014). Interobserver agreement was 0.86 (p < 0.001). Overall sensitivity and specificity of radiological prediction were 78.3% (95% CI, 68.6%-87.1%) and 96.4% (95% CI, 94.3%-97.8%) respectively. Overall PPV and NPV were 78.3% (95% CI, 67.6%-86.3%) and 96.8% (95% CI, 94.8%-98.1%) respectively. The sensitivity and PPV for aneurysms in the anterior communicating, anterior, and middle cerebral arteries appeared to be significantly higher than in other locations (p = 0.015 and 0.019 respectively). Analysis of independent predictive factors of correct radiological location revealed that ICH predisposes to a correct radiological diagnosis with an odds ratio of 8.57 (95% CI, 1.07-68.99; p = 0.03). CONCLUSIONS: NECT has a high diagnostic value in identifying the source of bleeding in patients with multiple aneurysms for anterior circulation aneurysms, especially with coexisting ICH. For other locations, NECT is not reliable enough to base treatment decisions upon.

Perineuronal Nets and Their Role in Synaptic Homeostasis.

Extracellular matrix (ECM) molecules that are released by neurons and glial cells form perineuronal nets (PNNs) and modulate many neuronal and glial functions. PNNs, whose structure is still not known in detail, surround cell bodies and dendrites, which leaves free space for synapses to come into contact. A reduction in the expression of many neuronal ECM components adversely affects processes that are associated with synaptic plasticity, learning, and memory. At the same time, increased ECM activity, e.g., as a result of astrogliosis following brain damage or in neuroinflammation, can also have harmful consequences. The therapeutic use of enzymes to attenuate elevated neuronal ECM expression after injury or in Alzheimer's disease has proven to be beneficial by promoting axon growth and increasing synaptic plasticity. Yet, severe impairment of ECM function can also lead to neurodegeneration. Thus, it appears that to ensure healthy neuronal function a delicate balance of ECM components must be maintained. In this paper we review the structure of PNNs and their components, such as hyaluronan, proteoglycans, core proteins, chondroitin sulphate proteoglycans, tenascins, and Hapln proteins. We also characterize the role of ECM in the functioning of the blood-brain barrier, neuronal communication, as well as the participation of PNNs in synaptic plasticity and some clinical aspects of perineuronal net impairment. Furthermore, we discuss the participation of PNNs in brain signaling. Understanding the molecular foundations of the ways that PNNs participate in brain signaling and synaptic plasticity, as well as how they change in physiological and pathological conditions, may help in the development of new therapies for many degenerative and inflammatory diseases of the brain.

The Pathophysiology of Post-Traumatic Glioma.

Malignant glioma is a brain tumor with a very high mortality rate resulting from the specific morphology of its infiltrative growth and poor early detection rates. The causes of one of its very specific types, i.e., post-traumatic glioma, have been discussed for many years, with some studies providing evidence for mechanisms where the reaction to an injury may in some cases lead to the onset of carcinogenesis in the brain. In this review of the available literature, we discuss the consequences of breaking the blood⁻brain barrier and consequences of the influx of immune-system cells to the site of injury. We also analyze the influence of inflammatory mediators on the expression of genes controlling the process of apoptosis and the effect of chemical mutagenic factors on glial cells in the brain. We present the results of experimental studies indicating a relationship between injury and glioma development. However, epidemiological studies on post-traumatic glioma, of which only a few confirm the conclusions of experimental research, indicate that any potential relationship between injury and glioma, if any, is indirect.

New extracellular factors in glioblastoma multiforme development: neurotensin, growth differentiation factor-15, sphingosine-1-phosphate and cytomegalovirus infection.

Recent years have seen considerable progress in understanding the biochemistry of cancer. For example, more significance is now assigned to the tumor microenvironment, especially with regard to intercellular signaling in the tumor niche which depends on many factors secreted by tumor cells. In addition, great progress has been made in understanding the influence of factors such as neurotensin, growth differentiation factor-15 (GDF-15), sphingosine-1-phosphate (S1P), and infection with cytomegalovirus (CMV) on the 'hallmarks of cancer' in glioblastoma multiforme. Therefore, in the present work we describe the influence of these factors on the proliferation and apoptosis of neoplastic cells, cancer stem cells, angiogenesis, migration and invasion, and cancer immune evasion in a glioblastoma multiforme tumor. In particular, we discuss the effect of neurotensin, GDF-15, S1P (including the drug FTY720), and infection with CMV on tumor-associated macrophages (TAM), microglial cells, neutrophil and regulatory T cells (Treg), on the tumor microenvironment. In order to better understand the role of the aforementioned factors in tumoral processes, we outline the latest models of intratumoral heterogeneity in glioblastoma multiforme. Based on the most recent reports, we discuss the problems of multi-drug therapy in treating glioblastoma multiforme.

[The ophthalmologic signs in cerebellum tumor. Preliminary report].

Introduction: The aim of the study was an analysis of ophthalmic symptoms coexisting with the tumour of the cerebellum. Material and methods: The study included 14 patients in the age between 21­55 years old with the tumor of cerebellum, who were operated in the Neurosurgery Clinic of the Pomeranian Medical University in Szczecin. The comprehensive ophthalmic examination were performed before and after 5 days from surgery. The examinations included evaluation of: pupillary reactions, visual acuity, fundus ophthalmoscopy, intraocular pressures, eye motility, visual field, optometrical tests and visual manual localization test. Results: The symptoms found before surgery of cerebellum tumors: diplopia (3 persons), early papilloedema (4 persons), nystagmus (2 persons), lack (5 persons) and weakened of convergence reô€lex (3 persons), latent strabismus (5 persons), manifest strabismus (3 persons). On the 5th day after the surgery were found: nystagmus (1 person), lack (5 persons) and weakened of the convergence reô€lex (3 persons). Visual manual localization was disparate depending on location of the tumor in the cerebellum; prevailed crossed and uncrossed localizations. Conclusions: 1. The natural dynamic of the tumor and surgical damage to the posterior cranial cavity structures can be monitored by assessment of the condition of the organ sight. 2. It is recommended to make the visual manual localization tests such as exponent disorders of senso-motorical deviations, which may occur in the patients with the cerebellum tumor.

Intracerebral metastasis of glioblastoma multiforme. Case report and literature review.

Glioblastoma multiforme is the most common primary malignant brain tumor in adults. It's characterized by a high malignancy and rapid, frequent tendency to local recurrence. Distant metastases disseminated in the brain compared to the primary lesion and outside the central nervous system are rarely reported in the literature. The case which is being presented is of a 53 year old man operated in 2008 because of Glioblastoma multiforme IV WHO in the left periventricular parietal region, in which the main symptoms were the Gerstmann syndrome, mixed aphasia and memory disturbance. The patient was operated totally followed by adjuvant radiotherapy and chemotherapy. Two years later epileptic seizures and aphasia were intensified. Due to this adverse symptoms MRI was ordered, which revealed a tumor in the left periventricular temporal region in different location compared to the primary lesion. The patient was operated by temporal lobectomy. Histopathological diagnosis was Glioblastoma multiforme IV WHO. According to the literature we analyzed the natural GBM tumor features and factors responsible for possibility to appear of the same type of tumor in another location of the brain.

[Malignant astrocytoma as a recurrance of astrocytoma II WHO after 13 years. Case report and literature review]. / Wznowa gwiazdziaka II stopnia wg WHO w formie uzlosliwionej po 13 latach. Opis przypadku i przeglad pismiennictwa.

Astrocytomas--neroepithelial originated tumors that belong to the big, differential group of tumors, which derive from astrocytic glial. They include slow growing tumors such as fibillary astrocytoma or very malignant glioblastoma multiforme. The case which is being presented is of a forty nine year old woman operated in July 1997 because of a protoplasmic astrocytoma II WHO in the left frontal lobe. The main symptoms were epilepsy seizures. The patient was operated totally followed by adjuvant radiotherapy. 13 years later epilepsy seizures with syncope showed up again. Due to this adverse event MRI was ordered and suspicion of tumor recurrence was put forward. The lesion was removed radically with a neuronavigation guided technique. Histopathology identified anaplastic astrocytoma III WHO. According to literature, the factors regarding remission time, tumor malignancy and therapeutic aim were analyzed.

[Surgery with neuronavigated mapping of cerebral cavernoma evoking epileptic seizures]. / Leczenie operacyjne naczyniaka jamistego mózgu wywolujacego napady padaczkowe przy uzyciu mapowania neuronawigacyjnego.

INTRODUCTION: Cavernous hemangioma is increasingly recognized as the cause of epilepsy attributed to vasogenic foci. The clinical picture of this lesion is notable for epileptic seizures and intracerebral hemorrhage. Surgical excision of cavernoma remains the most effective antiepileptic modality. Good results of surgery are achieved with the use of modern operative procedures such as stereotaxy and neuronavigation. MATERIAL AND METHODS: Twelve patients with cavernous hemangioma were operated at the Department of Neurosurgery and Pediatric Neurosurgery, Pomeranian Medical University, Szczecin, between 1999 and 2008. This group included 10 females aged 7-54 years (mean 24.8 years) and 2 males aged 14-49 years (mean 31.5 years), 7 children (58.3%) and 5 adults (41.7%). Seven patients (58.3%) presented with generalized and the remaining 5 patients (41.7%) with secondarily generalized seizures. The mean time from onset of seizures to surgery was 2.6 months. All patients were operated using preoperative neuronavigated mapping to determine the optimal access to the lesion followed by neuronavigation-guided cavernoma excision. Postoperative neurological status was assessed with GOS scale and antiepileptic treatment outcome with Engel's scale as modified by Moran. RESULTS: The caveroma was completely removed in each case. Postoperative follow-up time was 2-59 months (mean 30.3 months). Neurological status of all patients was category 5 of the GOS scale. Engel's class I outcome was achieved in all patients. Nine patients (75%) were weaned off antiepileptic drugs following normalization of EEG. CONCLUSIONS: The following conclusions were drawn basing on the findings of this study: (1) Neuronavigation offers high precision and low traumatization which reduce the risk of neurological sequellae (neurological deficits and epilepsy) in patients operated for cavernoma; (2) Early resection of cavernoma offers the chance of curing epilepsy.

[Sudden loss of vision as the result of the decompression after the removal of the arachnoid cyst of the temporal region. A case report]. / Nagle zaniewidzenie jako nastiepstwo dekompresji po usunieciu torbieli pajeczynówki okolicy skroniowej. Opis przypadku.

INTRODUCTION: The neurosurgical treatment of arachnoid cyst consist in evacuation of the cyst and in consequence the decrease of the endocranial pressure. From the neurosurgical point of view, both the endocranial hypertension and the sudden hypotension inside a skull after a surgical motion are very dangerous. The sudden loss of vision is the most adverse surgical complication for the patient. The aim of the work is the presentation of the child, who suddenly and completely lost the sight after performing a neurosurgical evacuation of the cyst of the arachnoidea. CASE REPORT: We introduce 6-year-old boy, who went blind after executed puncture of the arachnoidea cyst of temporal region of the brain. The dramatic, sudden lack of the feeling of light perception that lasted for about 2 weeks caused confusion and anxiety of the child. The vision slowly began to come back as time goes by, at first light perception recovered in one eye, and only after several months in the second eye too. Ptosis of one of the eyelid subided entirely. We observed the diminution of the squint angle, which appeared after the surgical intervention, as the result of applied treatment too. DISCUSSION: The mechanism of the origin of this occurrence has not been fully identified, most likely it comes into being as a result of disturbances in the microcirculation of the optical nerve and the chiasma optical. The boy has been treated three times with Trental during the first year. After eight months from the incident of loss of vision, the acuity vision in right eye was 1/50 and 0.2 in left eye. We applied the intensive treatment of amblyopia and squint according to Szczecin's school of the strabismus treatment. The child obtained the improvement of the eyesight in the right eye to 0.1 and in the left eye to 0.9 (according to Snellen test). CONCLUSION: The operative treatment of the arachnoidea cyst is an efficient conduct, though, at times complications happen which make the result of the treatment worse.

[Post-traumatic unilateral vision loss caused by carotid-cavernous fistula]. / Pourazowa utrata widzenia jednego oka spowodowana przetoka tetniczo-jamista.

PURPOSE: We show the subject with unilateral vision loss after head trauma. The carotid-cavernous fistula was a cause of one eye blindness recognized after 2 months. MATERIAL AND METHODS: 21 years old student with hard trauma of the head and brain after traffic accident. He had skull bones without optic canals bones broke. After 2 months he came to the Ophthalmology Clinic with no light perception, proptosis and swelling of conjunctiva and disturbances of motility of the left eye. We suspected a carotid-cavernous fistula as a cause of loss of light perception in this eye. The patient was sent to Neurosurgery Clinic where he had left carotid artery in the brain closed. RESULTS: After 8 days from the surgery he was in good physical condition but we didn't save the vision of the left eye.

[Diagnosis of brain gliomas in stereotactic biopsy assisted by optical neuro-navigation system]. / Diagnostyka glejaków mózgu pobranych droga biopsji stereotaktycznej wspomaganej optycznym systemem neuronawigacji.

BACKGROUND AND PURPOSE: Recently, stereotactic procedures of brain tumours have been enriched by an optical neuronavigation system, enabling us to assess the tumour location and size by means of three-dimensional magnetic resonance imaging (MRI). The aim of the study was to check which areas of brain gliomas would be most useful in neuropathological diagnosis of the material taken during stereotactic biopsy. We also analysed whether the MRI processed in the computerised neuronavigation system would be reliable in determination of a safety margin of glioma resection. MATERIAL AND METHODS: Material from the stereotactic biopsy has been examined neuropathologically by means of the Stealth Station navigation system. Tissue specimens were taken from the centre of neoplasm, its intermediate area, edge of the tumour and the nearest vicinity of neoplasm. 2-3 specimens in each area of the tumour were taken. The material was fixed in buffered formalin and embedded in paraffin and then stained with hematoxylin and immunostained for GFAP, cytokeratin and vimentin. RESULTS: Astrocytomas II were diagnosed in 17 cases, including fibrillary astrocytoma in 13 cases and gemistocytic astrocytoma in 2 cases. In other cases protoplasmatic astrocytomas were suspected. In 6 cases anaplastic astrocytoma and in 16 cases glioblastoma multiforme were diagnosed. In 3 cases the degree of malignancy was not possible to be defined. In 2 cases the neoplasm was not found. "Sensitivity" of the method was 91.1% and its "specificity" was 82.2%. The best results were achieved analysing the material from the intermediate area of neoplasm. There was the lowest number of "false negative" diagnostic results in this area. A few positive results were found in the central area and a high number of results (almost 50%) could be defined as "negative", assuming the specimens with no neoplastic cells. In more than 40% of biopsies from the edge of the tumour, neoplasm was not found, while in more than 20% of biopsies from the nearest vicinity of the tumour, neoplastic cells were present. CONCLUSIONS: Intermediate zone of brain gliomas located between its central parts and the tumour edge appears to be the most appropriate neoplastic area for diagnostic stereotactic biopsy assisted by the optical neuronavigation system. Because of infiltrative character of brain gliomas as well as their real dislocation during surgical procedure compared to the position based on the earlier neuroimaging, the territories considered in the optical neuronavigation system as the vicinity or neoplastic edge, run a risk of neuropathological misdiagnosis in this biopsy.