Evolutionary model of brain tumor circulating cells: Cellular galaxy.

BACKGROUND: Although circulating tumor cells (CTCs) have been the focus of consideration for a decade, a categorized cell-based diagnostic strategy is unavailable. The personalized management and complementary/analytical-strategy of data require an alphabetic guide. Therefore, we aimed to determine the behavior of CTCs in tumor and blood in order to provide the hypothetical-based agenda in the brain neoplasms. Exploring the protein expression (PE) using a single cell-based method would clarify the heterogeneity and diversity in tumor and blood, which are key events in the evolution in brain tumors. In fact, heterogeneity, diversity, and evolution are required for cancer initiation and progression. AIM: To explore CTCs in brain tumors and blood cells and to assay intensity of PE through personalized insight. METHODS: The focal population included 14 patients with meningioma, and four patients with metastatic brain tumors (T). PE was assayed by immunofluorescence in tumors cells and CTCs in 18 patients with brain tumors. Ratio test was applied between the T cells and CTCs in tumor tissue and in vascular system. T/CTC ratio-based classification of PE in macrophage chemoattractant chemokine ligand 2 (CCL2), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), CD133, cyclin E, neurofilament marker, cytokeratin 19, and leukocyte common antigen (CD45) were investigated. RESULTS: Total analyzed cells ranged between 10794-92283 for tumor cells and between 117-2870 for CTCs. Characteristics of histopathologic and status of an ataxia-telangiectasia mutated polymorphism (D1853N) in 18 patients affected with brain tumors were also provided. The course of evolution and metastatic event relied on the elevated protein expression in CTCs, which could be considered as a prognostic value. Diverse protein expression of the migrated cells into the blood stream and the tumor was indicative of the occurrence of evolution. Besides, the harmonic co-expression between CCL2/EGF and CCL2/VEGF could facilitate the tumor progression including the metastatic event. Expression of these proteins in the migrated vasculature and into the buccal tissue offered a non-invasive follow-up detection in neoplastic disorders. PE-exploration of neurofilament marker/CD133/VEGF of the CTCs in meningioma and cytokeratin 19/CD45/ cyclin E in the patients with metastatic brain tumor would clarify the tumor biology of the brain neoplastic disorders. CONCLUSION: The alphabetical base of the evolutionary mechanisms relies on dual-, triple-, and multi-models with diverse intensity of expression. In fact, cross-talk between initiative and the complementary channels defines the evolutionary insight in cancer. A diverse-model of protein expression, including low, medium, and high intensity, is the key requirement for the completed model. The cluster of cells with diverse expression and remarkable co-expression between CCL2/EGF/VEGF and NM/CD133/VEGF in CTCs may be indicative of probable invasiveness of the tumor. Furthermore, the mode of cytokeratin-19+/CD45- can be traced in the metastatic patients.

Prognostic significance of MYCN gene amplification and protein expression in primary brain tumors: Astrocytoma and meningioma.

BACKGROUND: Astrocytoma and meningioma are the most common primary brain tumors. MYCN as a member of MYC proto-oncogenes has recently appeared as an attractive therapeutic target. Functions of MYCN are critical for growth of nervous system and neural differentiation. OBJECTIVE: We examined MYCN amplification and protein expression in astrocytoma and meningioma cases. METHODS: In this study, we used real-time PCR, FISH assay and flowcytometry to analyze DNA amplification and protein expression of MYCN. RESULTS: Among 30 samples of brain tumor, 14 cases (46.6%) revealed MYCN amplification. High-protein expression of MYCN was also observed in 43.3% of patients. There was a significant correlation between MYCN gene amplification and protein expression (r= 0.523; p= 0.003), interestingly five case showed discrepancy between the gene amplification and protein expression. Although MYCN amplification fails to show correlation with poor prognosis (p= 0.305), protein high-expression of MYCN significantly reduce disease-free survival (p= 0.019). CONCLUSIONS: Our results challenge the concept of the neural specificity of MYCN by demonstrating contribution of MYCN in meningioma. Moreover, this study highlights the importance of research at both level of DNA and protein, to determine the biological functions and medical impacts of MYCN.

Telomerase activity in human brain tumors: astrocytoma and meningioma.

Somatic cells do not have telomerase activity but immortalized cell lines and more than 85 % of the cancer cells show telomerase activation to prevent the telomere from progressive shortening. The activation of this enzyme has been found in a variety of human tumors and tumor-derived cell lines, but only few studies on telomerase activity in human brain tumors have been reported. Here, we evaluated telomerase activity in different grades of human astrocytoma and meningioma brain tumors. In this study, assay for telomerase activity performed on 50 eligible cases consisted of 26 meningioma, 24 astrocytoma according to the standard protocols. In the brain tissues, telomerase activity was positive in 39 (65 %) of 50 patients. One sample t test showed that the telomerase activity in meningioma and astrocytoma tumors was significantly positive entirely (P < 0.001). Also, grade I of meningioma and low grades of astrocytoma (grades I and II) significantly showed telomerase activity. According to our results, we suggest that activation of telomerase is an event that starts mostly at low grades of brain including meningioma and astrocytoma tumors.

Complementary effect of H MRS in diagnosis of suprasellar tumors.

OBJECTIVE: Suprasellar tumors are considered exceptionally important in neurosurgical practice due to their proximity to vital portions of the brain. Predicting histology of these tumors is of prime importance in determining the surgical approach, prognosis, and probable postoperative complications. There are numerous cases where computed tomography and magnetic resonance imaging (MRI) fail to predict histology. We have studied the role of magnetic resonance spectroscopy (MRS) in the diagnosis of suprasellar tumors. METHODS: Twenty-three patients with primary nonfunctional suprasellar tumors and high-quality magnetic resonance spectra were studied. The most probable diagnosis (adenoma, meningioma, craniopharyngioma, or astrocytoma) was made by a neuroradiologist based on the MRI findings and then based on MRI plus MRS findings. Finally, the results were compared with the pathology report. RESULTS: The information provided by MRS led the radiologist to alter his prior diagnosis that was based on the MRI in four patients, and the final diagnoses were in accordance with the histopathology. Wrong diagnosis was made by MRI plus MRS in three patients. Test efficiency of MRI was 69.6%, and it was 87% for MRI plus MRS. However, the difference was not statistically significant (P value=.152). CONCLUSION: MRS may be useful in providing a more improved preoperative diagnosis of suprasellar tumors.

Prospective evaluation of technetium-99m ECD SPET in mild traumatic brain injury for the prediction of sustained neuropsychological sequels.

Our aim was to evaluate whether single photon emission tomography (SPET) versus computed tomography (CT) in acute phase of mild traumatic brain injury (MTBI) was better for the prediction of sustained neuropsychological symptoms beyond a typical recovery period. Forty five patients with MTBI were prospectively evaluated with clinical and neuropsychological exams, structural imaging using CT and perfusion study by(99m)Tc-ethylene cysteinate dimer ((99m)Tc-ECD) SPET within a week of the head trauma. After an interval ranging from 6 to 12 (median: 9) months, all patients were re-evaluated by standard neuropsychological tests for the assessment of sustained personality changes, imbalance and memory deficits. Our results showed that, 25 patients had abnormal brain perfusion on (99m)Tc-ECD SPET. In 19 cases of total 20 normal (99m)Tc-ECD SPET studies, no sign of memory deficit and imbalance was observed. Negative predictive value (NPV) for both complications was 95%. NPV of CT for the prediction of memory deficit and imbalance were 77.4% and 90.3%, respectively. The risk of developing sustained memory deficits and imbalance in patients with positive (99m)Tc-ECD SPET were 40% and 20%, respectively. A perfusion abnormality on (99m)Tc-ECD SPET was associated with a greater chance of long-standing memory deficits (odds ratio=13.49, P=0.020)while neither CT nor (99m)Tc-ECD SPET could independently predict the personality changes in these patients. The patients with abnormalities on both CT and SPET images faced a significant relative risk of complications, 1.63 times, higher than the others. In conclusion, our study indicated that (99m)Tc-ECD SPET imaging or CT imaging alone, could not predict the occurrence of sustained complications after MTBI. Concurrent use of both imaging modalities performed shortly after MTBI may yield the best results, as the combination of abnormalities in both cerebral structure and perfusion could indicate the patients with 1.63 times higher risk of sustained memory deficits, personality changes and imbalance.

Evolutionary hypothesis of telomere length in primary breast cancer and brain tumour patients: a tracer for genomic-tumour heterogeneity and instability.

It was previously reported that tumour samples had shorter telomeres than the surrounding normal tissue. Hereby, the initial sign of correlation between malignant tissue and telomere behaviour could be noticed. Bridging knowledge between germ and somatic cells could facilitate understanding cellular evolution. The aim of our investigation was to provide evidence for the evolutionary hypothesis of TL (telomere length) in primary BC (breast cancer) and BTs (brain tumours), which might be applied as a prognostic and/or predictive marker. DNA extraction from the frozen tissues was performed using high pure PCR template preparation kit. Standard protocol of Telo TTAGGG Telomere Length Assay kit, a non-radioactive chemiluminescent assay, was used. The protein expression in extracted cells was analysed by immunofluorescence. We also detected telomerase activity. The G/T (genomic/tumour ratio) for TL in two groups of patients affected with primary BC and primary BT revealed significant differences in both BC patients (P = 0.025) and in BTs (P = 0.001). The pattern of telomere signals by Q-FISH (quantitative fluorescent in situ hybridization) show that in all samples, except one, SI (signal intensity) has been significantly decreased in tissue related to blood, either in BC patients or in patients with BTs (0.041≥P≥0.001). However, the data achieved by Q-FISH support the results of Southern blot. These data reflect a significant diversity either in BC or in BT patients, providing evidence for the evolutionary hypothesis of TL in cancer development and progression.

Alterations of telomere length in human brain tumors.

Telomeres at the ends of human chromosomes consist of tandem hexametric (TTAGGG)n repeats, which protect them from degradation. At each cycle of cell division, most normal somatic cells lose approximately 50-100 bp of the terminal telomeric repeat DNA. Precise prediction of growth and estimation of the malignant potential of brain tumors require additional markers. DNA extraction was performed from the 51 frozen tissues, and a non-radioactive chemiluminescent assay was used for Southern blotting. One sample t-test shows highly significant difference in telomere length in meningioma and astrocytoma with normal range. According to our results, higher grades of meningioma and astrocytoma tumors show more heterogeneity in telomere length, and also it seems shortening process of telomeres is an early event in brain tumors.

Early post operative visual outcome in microsurgically treated suprasellar meningiomas predict long-term visual outcome.

BACKGROUND: Different data exist regarding long-term visual prognosis associated with suprasellar meningiomas. The aim of this study was to determine the outcome of suprasellar meningiomas with respect to short and long-term visual outcomes. METHOD: During the period of 1997 to 2006, 45 patients were operated either through a pterional (30) or bifrontal (15) approach. Visual parameters were evaluated early and late post-operatively. RESULTS: 5 patients died post-operatively and 2 cases failed to attend follow up. During the early post-operative period, 15 (39.5%) showed improvement and 9 (23.7%) worsening of vision among 38 patients. Patients were followed-up for 1 to 8 years with mean of 4.1 years. Follow-up data revealed that 26 (68.4%) patients had visual improvement in at least one eye (10 of them in both eyes) while 10 (26.3%) patients had visual deterioration in one or both eyes. Data showed no significant correlation between visual outcome and extent of tumor removal or surgical approach. Visual outcome was better in patients with preoperative vision > 1mfc (p-value=0.001). Data also showed that early post-op vision significantly correlates with long term visual outcome (p-value =0.003). CONCLUSION: Visual outcome is better in patients with preoperative vision > 1 mfc and early post-operative vision significantly correlates with long term visual outcome.

ABO blood group frequency and brain tumors.

The influence of blood group types on development of brain tumors is unclear since there are conflicting reports from surveys regarding the distribution of ABO blood groups and primary intracranial neoplasms. The present descriptive, retrospective study was therefore made of 907 patients with reliable records for ABO blood groups and proven histological diagnosis who were hospitalized with brain tumors at the Shariati Hospital neurosurgical center, between 1980 and2002. The distribution of the ABO blood groups in this study population was compared with that in the general population by the chi-square test. Data analysis showed that there are no significant differences between types of intracranial tumors and frequencies of four major blood groups. The distribution of the ABO blood groups in patients did not differ significantly from that of the general population. Of our patients with craniopharyngioma, however, significantly more were in group A (P<0.05) compared with the general population of Iran.