scholarly journals Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker

2011 ◽  
Vol 115 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Pablo A. Valdés ◽  
Frederic Leblond ◽  
Anthony Kim ◽  
Brent T. Harris ◽  
Brian C. Wilson ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Fluorescence Imaging ◽  
Low Grade ◽  
Normal Brain ◽  
Intracranial Tumors ◽  
Neoplastic Tissue ◽  
Fluorescence Measurements ◽  
Significant Difference ◽  
Quantitative Fluorescence

Object Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following δ-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies. Methods The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board–approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo. Results A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon's visual perception were classified correctly in an analysis of all tumors. Conclusions These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of intracranial tumors.

scholarly journals Protein Kinase A Distribution in Meningioma

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1686 ◽  
Author(s):  
Caretta ◽  
Denaro ◽  
D’Avella ◽  
Mucignat-Caretta
Keyword(s):  
Brain Tissue ◽  
Catalytic Subunit ◽  
Therapeutic Interventions ◽  
Normal Brain ◽  
Local Concentration ◽  
Correlation Pattern ◽  
Catalytic Subunits ◽  
Tissue Specimens ◽  
Pka Catalytic Subunit

Deregulation of intracellular signal transduction pathways is a hallmark of cancer cells, clearly differentiating them from healthy cells. Differential intracellular distribution of the cAMP-dependent protein kinases (PKA) was previously detected in cell cultures and in vivo in glioblastoma and medulloblastoma. Our goal is to extend this observation to meningioma, to explore possible differences among tumors of different origins and prospective outcomes. The distribution of regulatory and catalytic subunits of PKA has been examined in tissue specimens obtained during surgery from meningioma patients. PKA RI subunit appeared more evenly distributed throughout the cytoplasm, but it was clearly detectable only in some tumors. RII was present in discrete spots, presumably at high local concentration; these aggregates could also be visualized under equilibrium binding conditions with fluorescent 8-substituted cAMP analogues, at variance with normal brain tissue and other brain tumors. The PKA catalytic subunit showed exactly overlapping pattern to RII and in fixed sections could be visualized by fluorescent cAMP analogues. Gene expression analysis showed that the PKA catalytic subunit revealed a significant correlation pattern with genes involved in meningioma. Hence, meningioma patients show a distinctive distribution pattern of PKA regulatory and catalytic subunits, different from glioblastoma, medulloblastoma, and healthy brain tissue. These observations raise the possibility of exploiting the PKA intracellular pathway as a diagnostic tool and possible therapeutic interventions.

scholarly journals Glutathione S-Transferases and Cytochrome P450 Enzyme Expression in Patients with Intracranial Tumors: Preliminary Report of 55 Patients

2018 ◽  
Vol 28 (1) ◽  
pp. 56-62
Author(s):  
Cahit Kural ◽  
Arzu Kaya Kocdogan ◽  
Gulcin Güler Şimşek ◽  
Serpil Oğuztüzün ◽  
Pınar Kaygın ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Brain Tissue ◽  
Pituitary Adenomas ◽  
Normal Brain ◽  
Cytochrome P450 Enzyme ◽  
Intracranial Tumors ◽  
Glutathione S Transferase ◽  
Normal Brain Tissue ◽  
Tissue Samples ◽  
P450 Enzyme

Objective: Intracranial tumors are one of the most frightening and difficult-to-treat tumor types. In addition to surgery, protocols such as chemotherapy and radiotherapy also take place in the treatment. Glutathione S-transferase (GST) and cytochrome P450 (CYP) enzymes are prominent drug-metabolizing enzymes in the human body. The aim of this study is to show the expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 in different types of brain tumors and compare our results with those in the literature. Subjects and Methods: The expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 was analyzed using immunostaining in 55 patients with intracranial tumors in 2016–2017. For GST and CYP expression in normal brain tissue, samples of a portion of surrounding normal brain tissue as well as a matched far neighbor of tumor tissue were used. The demographic features of the patients were documented and the expression results compared. Results: The mean age of the patients was 46.72 years; 29 patients were female and 26 were male. Fifty-seven specimens were obtained from 55 patients. Among them, meningioma was diagnosed in 12, metastases in 12, glioblastoma in 9, and pituitary adenoma in 5. The highest GSTP1, GSTM1, and CYP­1A1 expressions were observed in pituitary adenomas. The lowest GSTP1 expression was detected in glioblastomas and the lowest CYP1B1 expression in pituitary adenomas. Conclusion: GSTP1 and CYP expression is increased in intracranial tumors. These results should be confirmed with a larger series and different enzyme subtypes.

scholarly journals Determination of SOX9 Gene Expression In Brain Tumours Among East Coast Malaysia Population

2020 ◽  
Vol 18 (2) ◽  
Author(s):  
Md Dzali NB ◽  
Wan Taib WR ◽  
Zahary MN ◽  
Abu Bakar NH ◽  
Abd Latif AZ ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Brain Tumour ◽  
Brain Tumours ◽  
East Coast ◽  
Rna Extraction ◽  
Slight Modification ◽  
Low Grade ◽  
Normal Brain ◽  
Sox9 Expression ◽  
Sox9 Gene

Introduction: SOX9, a members of SOX family, plays a significant roles in developmental processes during embryogenesis, including brain tissue. Few studies have shown that SOX9 has been involved in tumourigenesis of several types of cancer including brain tumour. However, such studies are still lacking in the Malaysian population. The aim of this study was to determine SOX9 expression level in several types of brain tumours in East Coast Malaysia. Materials and Methods: Five formalin-fixed pariffin-embedded brain tumour samples of Malay descendants were sectioned by using microtome. RNA extraction was performed with slight modification by adding Trizol during tissue lysis. The RNA was converted to cDNA using reverse transcription technique before SOX9 expression was detected using RT q-PCR assay in brain tumours normalized to non-neoplastic brain tissues. Results: Overall results displayed that SOX9 gene in all samples were up-regulated. SOX9 overexpression was found in both high and low grade glioma (anaplastic and pilocytic astrocytoma respectively). This is consistence with both low grade (benign) and atypical meningioma. Secondary brain tumour also showed up-regulation when compared to normal brain tissue. Conclusion: Up-regulation in SOX9 expression in selected brain tumours in Malay patients revealed its significant roles in brain tumourigenesis. Functional studies should be carried out to observe the SOX9 functions and mechanism whether they should reflect their diverse roles in Malaysia population.

Differential retention of rhodamine 123 by avian sarcoma virus-induced glioma and normal brain tissue of the rat in vivo

Cancer ◽  
1987 ◽  
Vol 59 (2) ◽  
pp. 266-270 ◽  
Author(s):  
William C. Beckman ◽  
Stephen K. Powers ◽  
J. Tony Brown ◽  
G. Yancey Gillespie ◽  
Darell D. Bigner ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Rhodamine 123 ◽  
Normal Brain ◽  
Avian Sarcoma Virus ◽  
Normal Brain Tissue ◽  
Differential Retention ◽  
Sarcoma Virus ◽  
Avian Sarcoma

scholarly journals New Light on the Brain: The Role of Photosensitizing Agents and Laser Light in the Management of Invasive Intracranial Tumors

2003 ◽  
Vol 2 (4) ◽  
pp. 303-309 ◽  
Author(s):  
M. Sam Eljamel
Keyword(s):  
Brain Tissue ◽  
Malignant Gliomas ◽  
Surgical Excision ◽  
Normal Brain ◽  
Full Potential ◽  
Intracranial Tumors ◽  
Dismal Prognosis ◽  
Photosensitizing Agents ◽  
The Brain

Invasive intracranial tumors, particularly malignant gliomas, are very difficult to eradicate surgically and carry a dismal prognosis. The vast majority relapse locally indicating that their cure is dependent on radical and complete local excision. However, their ability to invade and hide among normal brain tissue, our inability to visualize and detect them, the low tolerance of brain tissue to ionizing radiation and the presence of the blood brain barrier are the main causes of our failure to eradicate them. Photodynamic detection with 100% specificity and more than 80% sensitivity offers an excellent chance of visualizing camouflaged tumor nests. Also, photodynamic therapy offers a very good chance of targeted destruction of the remaining tumor cells safely following surgical excision and may double the survival of patients harboring these awful tumors. More work needs to be done to refine this promising technology to exploit it to its full potential.

Transferrin receptor in normal and neoplastic brain tissue: implications for brain-tumor immunotherapy

1990 ◽  
Vol 72 (6) ◽  
pp. 941-945 ◽  
Author(s):  
Lawrence Recht ◽  
Carmen O. Torres ◽  
Thomas W. Smith ◽  
Vic Raso ◽  
Thomas W. Griffin
Keyword(s):  
Brain Tumor ◽  
Brain Tissue ◽  
Transferrin Receptor ◽  
Malignant Tumors ◽  
Staining Pattern ◽  
Tumor Immunotherapy ◽  
Normal Brain ◽  
Human Brain Tissue ◽  
Neoplastic Tissue ◽  
Intense Staining

✓ The distribution of transferrin receptor (TfR) in normal human brain-tissue obtained at autopsy and in brain-tumor biopsy specimens from 27 patients was determined by immunohistochemistry using two specific murine monoclonal antibodies against human TfR. The tumors studied included 10 glioblastomas multiforme (GBM's), nine other glial tumors, and eight meningiomas. In normal brain, TfR was detected primarily in endothelial cells; rare glial cells also contained immunoreactive product. All tumors contained TfR-positive cells, although the intensity (number of cells stained) and pattern (focal vs. diffuse) of staining varied with the histopathological type of the tumor. Among gliomas, the most intense staining was seen in GBM's, especially in areas of pseudopalisading where virtually all cells were stained. A rough correlation between tumor grade, number of positively stained cells, and staining pattern was seen in the other astrocytic tumors. By contrast, all meningiomas demonstrated an identical and characteristic focal staining pattern. Considering the differential immunostaining for TfR between normal and neoplastic tissue, the authors conclude that TfR may be an appropriate target for monoclonal antibody-directed brain-tumor immunotherapy, especially in more malignant tumors such as GBM's.

scholarly journals Cerebral Blood Flow in Normal Brain Tissue of Patients with Intracranial Tumors

1996 ◽  
Vol 36 (10) ◽  
pp. 709-715 ◽  
Author(s):  
Yoshiya NAKAYAMA ◽  
Akira TANAKA ◽  
Shigehiko KUMATE ◽  
Shinya YOSHINAGA
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Tissue ◽  
Normal Brain ◽  
Intracranial Tumors ◽  
Normal Brain Tissue

scholarly journals The Expressions of Wnt/β-catenin Pathway-Related Components in Brainstem Gliomas

2013 ◽  
Vol 40 (3) ◽  
pp. 355-360 ◽  
Author(s):  
Wenhao Wu ◽  
Yongji Tian ◽  
Hong Wan ◽  
Yongmei Song ◽  
Junhua Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Clinicopathological Characteristics ◽  
Current Treatment ◽  
Brainstem Glioma ◽  
Low Grade ◽  
Normal Brain ◽  
Ki 67 ◽  
Significant Difference ◽  
The Relationship ◽  
Brain Tissues

Background:The overall prognosis of brainstem gliomas is very poor, and the current treatment cannot significantly prolong the overall survival of these patients; therefore, studying the molecular biological mechanisms of the occurrence and development of brainstem gliomas has important significance for their treatment. The Wnt/β-catenin signaling pathway is closely associated with the occurrence and development of tumors, but its relationship with brainstem gliomas remains unclear.Methods:This study used Western blot and immunohistochemistry methods to detect the expressions of Wnt/β-catenin signaling pathway-related components such as Wnt-1, Wnt-2, β-catenin and C-myc in six cases of normal brain tissues and 24 cases of brainstem gliomas and analyzed the relationship between their expressions and clinicopathological characteristics.Results:Wnt-1 had no obvious expression in normal brain tissues and did not show any significant difference between high- and low-grade brainstem gliomas; the expressions of Wnt-2, β-catenin and C-myc in high-grade brainstem gliomas were significantly higher than that in low-grade brainstem gliomas and normal brain tissues and were positively correlated with the expression of Ki-67. Moreover, the expressions of Wnt-2 and C-myc were significantly associated with the prognosis of brainstem glioma patients; additionally, there was a trend toward increased β-catenin expression with shorter survival, but there was no statistical difference.Conclusions:Wnt/β-catenin signaling pathway might be abnormally activated and plays an important role in the occurrence and development of brainstem gliomas. Wnt-2, β-catenin and C-myc may be potential targets for brainstem glioma treatment.

scholarly journals Multiple Irradiation Affects Cellular and Extracellular Components of the Mouse Brain Tissue and Adhesion and Proliferation of Glioblastoma Cells in Experimental System In Vivo

2021 ◽  
Vol 22 (24) ◽  
pp. 13350
Author(s):  
Maxim O. Politko ◽  
Alexandra Y. Tsidulko ◽  
Oxana A. Pashkovskaya ◽  
Konstantin E. Kuper ◽  
Anastasia V. Suhovskih ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Mouse Brain ◽  
Glial Cells ◽  
Ex Vivo ◽  
Experimental System ◽  
Normal Brain ◽  
Biosynthetic Activity ◽  
Normal Brain Tissue

Intensive adjuvant radiotherapy (RT) is a standard treatment for glioblastoma multiforme (GBM) patients; however, its effect on the normal brain tissue remains unclear. Here, we investigated the short-term effects of multiple irradiation on the cellular and extracellular glycosylated components of normal brain tissue and their functional significance. Triple irradiation (7 Gy*3 days) of C57Bl/6 mouse brain inhibited the viability, proliferation and biosynthetic activity of normal glial cells, resulting in a fast brain-zone-dependent deregulation of the expression of proteoglycans (PGs) (decorin, biglycan, versican, brevican and CD44). Complex time-point-specific (24–72 h) changes in decorin and brevican protein and chondroitin sulfate (CS) and heparan sulfate (HS) content suggested deterioration of the PGs glycosylation in irradiated brain tissue, while the transcriptional activity of HS-biosynthetic system remained unchanged. The primary glial cultures and organotypic slices from triple-irradiated brain tissue were more susceptible to GBM U87 cells’ adhesion and proliferation in co-culture systems in vitro and ex vivo. In summary, multiple irradiation affects glycosylated components of normal brain extracellular matrix (ECM) through inhibition of the functional activity of normal glial cells. The changed content and pattern of PGs and GAGs in irradiated brain tissues are accompanied by the increased adhesion and proliferation of GBM cells, suggesting a novel molecular mechanism of negative side-effects of anti-GBM radiotherapy.

Specific Imaging of Human Brain Tumor Xenografts Utilizing Radiolabelled Monoclonal Antibodies (MAbs)

1986 ◽  
Vol 25 (06) ◽  
pp. 210-215 ◽  
Author(s):  
C. J. Wikstrand ◽  
P. A. Humphrey ◽  
Y. S. Lee ◽  
R. E. Coleman ◽  
M. Zalutsky ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Normal Brain ◽  
Intracranial Tumors ◽  
Human Glioma ◽  
Human Brain Tumor ◽  
Tumor Xenografts ◽  
Hybridoma Technology ◽  
Time Specific ◽  
Radiolabelled Monoclonal Antibodies

At the present time, specific imaging and treatment of central nervous system malignancies is not possible. The development of monoclonal hybridoma technology may provide the solution to this problem. We have utilized human glioma-derived cell lines (HGCL) transplanted subcutaneously and intracranially into athymic mice and rats to evaluate the imaging and localizing properties of a panel of MAbs. MAbs 81C6, C12, and D12 and 81C6 Fab have shown significant in vivo localization against HGCL D-54 MG and 81C6 against U-251 MG when compared to equivalent non-specific MAbs. In subcutaneous D-54 MG-induced xenografts, maximal localization indices (LI) of up to 15.0 for 81C6, 6.8 for 81C6 Fab, 6.48 for C12, and 4.47 for D12 have been seen. The tumor-tissue ratios for normal brain have ranged from 235 for 81C6 to 167 for D12. The total percent injected dose for 81C6 was nearly 5% in U-251 MG tumors and 10% of the initial dose in D-54 tumors, while the percent injected dose for control MAb were 1.9% and 2.8%, respectively. Four subcutaneously growing U-251 MG tumors were clearly imaged using 1311-81C6. With intracranial growing D-54 MG,1311-81C6 provided external imaging of intracranial tumors at sizes as small as 20 mg while 131l-45.6, a non-specific MAb, provided imaging only when tumors achieved sizes greater than 300 mg. These data indicate that operationally specific MAbs and MAb Fab can specifically localize and be used to image human tumors transplanted into immunocompromised animals. The animal models described in this paper provide a sensitive method of evaluating MAbs in pre-human trials.

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