| 1. |
- Bisgin, Atil, et al.
(author)
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Interaction of CD200 Overexpression on Tumor Cells with CD200R1 Overexpression on Stromal Cells: An Escape from the Host Immune Response in Rectal Cancer Patients
- 2019
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In: Journal of Oncology. - : HINDAWI LTD. - 1687-8450 .- 1687-8469. ; 2019
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Journal article (peer-reviewed)abstract
- CD200 imparts an immunoregulatory signal through its receptor, CD200R1, leading to the suppression of tumor specific immunity. The mechanism of CD200:CD200R1 signaling pathway is still uncertain. Our aim was to investigate the expression and localization of CD200 and its receptor CD200R1 and their clinical significance in rectal cancer patients. We examined the immunohistochemical expressions and localizations of CD200 and CD200R1 in 140 rectal cancer patients. Among the patients, 79 underwent the preoperative radiotherapy and the others were untreated prior to the surgery. In addition, 121 matched normal rectal mucosa samples were evaluated. The results of immunohistochemical analysis showed a strikingly high level of CD200 in tumor cells (p=0.001) and CD200R1 expression in normal mucosal epithelium and stromal cells. Importantly, CD200R1 was overexpressed in stromal cells of the metastatic cancer patients compared to patients without metastases (p=0.002). More than that, 87% of metastatic patients had a phenotype of upregulated CD200 in tumor cells accompanied by overexpressed CD200R1 in stromal cells. In addition, low levels of CD200 were correlated with improved overall survival in untreated patients. We showed that tumor-stroma communication through CD200 and its receptor interaction is selected in patients with high risk of relapse. High levels of these molecules support instigation of the far and local metastatic nest that provides solid ground for metastasis. Our current data also disclose a mechanism by which CD200:CD200R1 affects tumor progression and may strengthen the feasibility of targeting CD200 or CD200R1 as anticancer strategy.
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| 2. |
- Lambrou, GI, et al.
(author)
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Fractal dimensions of in vitro tumor cell proliferation
- 2015
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In: Journal of oncology. - : Hindawi Limited. - 1687-8450 .- 1687-8469. ; 2015, s. 698760-
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Journal article (peer-reviewed)abstract
- Biological systems are characterized by their potential for dynamic adaptation. One of the challenges for systems biology approaches is their contribution towards the understanding of the dynamics of a growing cell population. Conceptualizing these dynamics in tumor models could help us understand the steps leading to the initiation of the disease and its progression.In vitromodels are useful in answering this question by providing information over the spatiotemporal nature of such dynamics. In the present work, we used physical quantities such as growth rate, velocity, and acceleration for the cellular proliferation and identified the fractal structures in tumor cell proliferation dynamics. We provide evidence that the rate of cellular proliferation is of nonlinear nature and exhibits oscillatory behavior. We also calculated the fractal dimensions of our cellular system. Our results show that the temporal transitions from one state to the other also follow nonlinear dynamics. Furthermore, we calculated self-similarity in cellular proliferation, providing the basis for further investigation in this topic. Such systems biology approaches are very useful in understanding the nature of cellular proliferation and growth. From a clinical point of view, our results may be applicable not only to primary tumors but also to tumor metastases.
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| 3. |
- Wu, Wendy Yi-Ying, et al.
(author)
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Imaging Biomarkers as Predictors for Breast Cancer Death
- 2019
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In: Journal of Oncology. - : Hindawi Publishing Corporation. - 1687-8450 .- 1687-8469.
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Journal article (peer-reviewed)abstract
- Background. To differentiate the risk of breast cancer death in a longitudinal cohort using imaging biomarkers of tumor extent and biology, specifically, the mammographic appearance, basal phenotype, histologic tumor distribution, and conventional tumor attributes. Methods. Using a prospective cohort study design, 498 invasive breast cancer patients diagnosed between 1996 and 1998 were used as the test cohort to assess the independent effects of the imaging biomarkers and other predictors on the risk of breast cancer death. External validation was performed with a cohort of 848 patients diagnosed between 2006 and 2010. Results. Mammographic tumor appearance was an independent predictor of risk of breast cancer death (P=0.0003) when conventional tumor attributes and treatment modalities were controlled. The casting type calcifications and architectural distortion were associated with 3.13-fold and 3.19-fold risks of breast cancer death, respectively. The basal phenotype independently conferred a 2.68-fold risk compared with nonbasal phenotype. The observed deaths did not differ significantly from expected deaths in the validation cohort. The application of imaging biomarkers together with other predictors classified twelve categories of risk for breast cancer death. Conclusion. Combining imaging biomarkers such as the mammographic appearance of the tumor with the histopathologic distribution and basal phenotype, accurately predicted long-term risk of breast cancer death. The information may be relevant for determining the need for molecular testing, planning treatment, and determining the most appropriate clinical surveillance schedule for breast cancer patients.
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| 4. |
- Zaravinos, A
(author)
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The Regulatory Role of MicroRNAs in EMT and Cancer
- 2015
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In: Journal of oncology. - : Hindawi Limited. - 1687-8450 .- 1687-8469. ; 2015, s. 865816-
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Journal article (peer-reviewed)abstract
- The epithelial to mesenchymal transition (EMT) is a powerful process in tumor invasion, metastasis, and tumorigenesis and describes the molecular reprogramming and phenotypic changes that are characterized by a transition from polarized immotile epithelial cells to motile mesenchymal cells. It is now well known that miRNAs are important regulators of malignant transformation and metastasis. The aberrant expression of the miR-200 family in cancer and its involvement in the initiation and progression of malignant transformation has been well demonstrated. The metastasis suppressive role of the miR-200 members is strongly associated with a pathologic EMT. This review describes the most recent advances regarding the influence of miRNAs in EMT and the control they exert in major signaling pathways in various cancers. The ability of the autocrine TGF-β/ZEB/miR-200 signaling regulatory network to control cell plasticity between the epithelial and mesenchymal state is further discussed. Various miRNAs are reported to directly target EMT transcription factors and components of the cell architecture, as well as miRNAs that are able to reverse the EMT process by targeting the Notch and Wnt signaling pathways. The link between cancer stem cells and EMT is also reported and the most recent developments regarding clinical trials that are currently using anti-miRNA constructs are further discussed.
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