ABSTRACT
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.
ABSTRACT
Background: Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) are involved in tumor development and progression. But, the classified-based data of protein expression (PE) in meningiomas is unavailable. Therefore, we aimed to explore the PE of VEGF and EGF in meningiomas by considering evolutionary strategy and the regional tumor-based assay. Methods: PE was assayed using immunofluorescence (IF) within the peripheral, central, and basal sections of four meningioma tumors, and a lung metastatic brain tumor as a positive control. Results: Diverse characteristics and harmonic cross-talk in the individual sections and between different tumor sections were traced. The mode of PE was puzzling and personalized issue. Co-expression had a key impact on tumor evolution and diverse PE profiles led to draw the heterogenic classification, as the personalized/complementary insight in the functional behavior of VEGF and EGF. D1853N polymorphism of ATM gene was mosaics in two patients with meningiomas. Conclusion: The classified heterogeneity, harmonic co-expression, and diverse functional information in different regions of tumors may lead to predict the aggressiveness mode of tumors as a translational insight to the clinical managements including therapy in brain tumors.
ABSTRACT
Few available data on the genomic-somatic evolution in breast cancer create limitation to provide the appropriate clinical managements. As an example, human subtelomeres (ST) are diverse-prone and variable targets. STs, as hot spots, have positive and negative impacts on the status of health and malady. We showed higher subtelomere signal copy number (SCN) of specific chromosomes in genomics than in auxiliary lymph node (ALN). Dissimilarity of signal intensity (SI) is found for all chromosomes. Significantly higher SI in genomics than in ALN cells were specified as chromosomes 5, 6, 9-12, 16-19 for weak; 1, 5-9, 19, X for medium; and 2, 5, 9, 10, 16, 18 for strong SI. For lacking, and presence of one and two SCNs; p/q ratio reflected differences for all chromosomes; but, 2, 3, 5, 7, 8, 10, 16, 18, 20, and X chromosomes were involved for three SCN. Chromosomes 1, 4, 9, 12, 17-19 lacked three SCN in ALN and lymphocytes. Weak SI ratio was higher in p- than in q-arm in majority of chromosomes. Manner of evolution and diversity in p- and q-arms is expressive of a novel definition as two diverse domains with a personalized insight. These data have been accompanied by periodic charts as ST array profiles which provide specific and individualized pattern in breast neoplasm. Such profiling at genomics level could be considered as a prediction through the patients' life. Moreover, subtelomere territory by interacting with protein expression of Ki67, cyclin D1, and cyclin E; and molecular targets including telomere length at genomics and somatic level provides package of information to bridge cancer cell biology to the cancer clinic as "puzzling paradigm."
