scholarly journals VEGF-R1/Flt-1 Receptor as a Characteristic of the Angiogenic Phenotype of Uveal Melanoma

2021 ◽  
Vol 18 (4) ◽  
pp. 866-875
Author(s):  
V. G. Likhvantseva ◽  
O. A. Anurova ◽  
S. E. Astakhova ◽  
M. V. Vereshchagina ◽  
V. E. Ovanesyan ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Uveal Melanoma ◽  
Molecular Genetic ◽  
Disease Stage ◽  
Hematogenous Metastasis ◽  
Important Indicator ◽  
Potential Target ◽  
Genetic Mechanisms

Thanks to new fundamental data, our understanding of the angiogenesis’ role and its molecular participants has changed. Molecular genetic mechanisms of activation of signaling pathways of proliferation, malignancy, suppression of the tumor cells’ apoptosis, carried out through the interaction of the VEGF molecule with its receptors, have been deciphered. Molecular genetic mechanisms of activation of signaling pathways of proliferation, malignancy, suppression of apoptosis of tumor cells, carried out through the interaction of the VEGF molecule with its receptors, have been deciphered. The doctrine of angiogenesis has changed. Angiogenesis began to be considered in the aspect of the increasing anaplasia mechanism, accelerating proliferation, the formation of a clone of stem tumor cells, highly resistant to chemotherapy and radiation therapy with a high potential for metastasis. It is time to reconsider the role of individual biological markers of angiogenesis in their suitability in predicting disease outcome and evaluating them as a potential target for targeted therapy. In this aspect, uveal melanoma (UM) as a model of an extremely aggressive malignant tumor using its angiogenic phenotype to accelerate hematogenous metastasis is of particular interest. One of the characteristics of the angiogenic phenotype is VEGF-R1/Flt-1. The purpose: to study the expression of the VEGF-R1/Flt-1 receptor as a characteristic of the angiogenic phenotype of UM in correlation with its clinical and morphological indicators and the outcome of the disease. The authors conducted a retrospective study on 98 archival paraffin blocks of the eyes of patients with UM. The following general patterns of Flt expression in UM cells are revealed: Basic expression takes place in the smallest tumor proliferates UM (T1). Moreover, overexpression (IGH-gradation III) of Flt in the nucleus (39.7 %) and cytoplasm (36.3 %) occurred in every third patient with UM in stage T1. The peak of reception for the maximum average percentage of positive cells and the average cellular IGH gradation of expression was recorded at the T2 stage, after which there was a slow decline to the T4 stage. The number of overexpressive Flt in the nucleus and cytoplasm of UM cells increased x 2 times (75.3 %) to the T2 stage. The peak of Flt nuclear expression in terms of the number of immunopositive cells was also recorded at the T2 stage. The authors concluded that VEGF-R1/Flt-1 expression is a very important characteristic of the UM angiogenic phenotype. In the vast majority of UM, there is an expression of the VEGF-R1/Flt-1 receptor in the nucleus and cytoplasm of tumor cells. The revealed correlations of VEGF-R1/Flt-1 expression with the volume and histological type of tumor, disease stage and metastasis allow them to consider Flt-1 an important indicator associated with the pathogenesis and prognosis of uveal melanoma and a potential target for targeted therapy. A prognostic adverse factor in the aspect of the prognosis of the risk of metastases should be considered the index of the ratio Flt C/Flt N ≥ 3.

scholarly journals Molecular-genetic mechanisms of initiation, promotion and progression of tumors

2017 ◽  
Vol 16 (4) ◽  
pp. 7-17 ◽  
Author(s):  
N. A. Lyzhko
Keyword(s):  
Tumor Cells ◽  
Genetic Instability ◽  
Molecular Genetic ◽  
Tumor Development ◽  
The Body ◽  
Number Of Patients ◽  
Depth Study ◽  
Genetic Mechanisms ◽  
Degree Of Malignancy

Carcinogenesis - the process of turning a normal cell into a tumor cell under the influence of the mutations that accumulate in the cell. The cause of tumor cells is the accumulation of her mutation. The accumulation of cell mutations occurs as a result of the occurrence of genetic instability. The process of tumor development is divided into 3 main stages: initiation, promotion and progression. At the stage of initiation of cell receives the first mutational hit, which leads to disruption of its genetic stability. Most often, mutations are subjected to proto-oncogenes, genes-tumor suppressors, and genes governing DNA repair processes. At this stage there is an accumulation in the cell genetic damage that lead to an increase of the degree of malignancy. The next step in the transformation of cells in a tumor is promoted. This period has transformed as a result of mutations cells acquire a number of properties that help it to survive in the environment. They no longer respond to signals from the environment, acquire, auto- and paracrine stimulation signals of proliferation, the inhibition of apoptosis, genetic instability, changes in the morphology of the cells, the lack of replicative aging. Cells of tumour clone is constantly mutating under the pressure of selection by the immune system of the body. This leads to qualitative changes of the phenotype of tumor cells, the emergence is one of many tumor clones. This stage is called “tumor progression”. As a result of increasing tumor mass requires greater amount of nutrients. The stimulation of angiogenesis. By reducing the degree of affinity of the cells to the substrate and increase its mobility, there are secondary foci, metastases. The development of tumor process captures new areas in the body in Spite of the constant improvement of methods of therapy of tumors, the number of patients who achieve long-term remission is not great. So researchers are looking for ways for more complete and in-depth study of the pathogenesis of tumors, since this will facilitate the development of more effective approaches to therapy of tumors. This article briefly describes the main stages of tumor development.

scholarly journals The Roles Played by Long Non-Coding RNAs in Glioma Resistance

2021 ◽  
Vol 22 (13) ◽  
pp. 6834
Author(s):  
Yeonsoo Chae ◽  
Jungwook Roh ◽  
Wanyeon Kim
Keyword(s):  
Signaling Pathways ◽  
Expression Profiles ◽  
Molecular Genetic ◽  
Glioma Cells ◽  
Disease Stage ◽  
Migration And Invasion ◽  
Therapeutic Resistance ◽  
Genetic Characteristics ◽  
Promote Cell Proliferation ◽  
Non Coding Rnas

Glioma originates in the central nervous system and is classified based on both histological features and molecular genetic characteristics. Long non-coding RNAs (lncRNAs) are longer than 200 nucleotides and are known to regulate tumorigenesis and tumor progression, and even confer therapeutic resistance to glioma cells. Since oncogenic lncRNAs have been frequently upregulated to promote cell proliferation, migration, and invasion in glioma cells, while tumor-suppressive lncRNAs responsible for the inhibition of apoptosis and decrease in therapeutic sensitivity in glioma cells have been generally downregulated, the dysregulation of lncRNAs affects many features of glioma patients, and the expression profiles associated with these lncRNAs are needed to diagnose the disease stage and to determine suitable therapeutic strategies. Accumulating studies show that the orchestrations of oncogenic lncRNAs and tumor-suppressive lncRNAs in glioma cells result in signaling pathways that influence the pathogenesis and progression of glioma. Furthermore, several lncRNAs are related to the regulation of therapeutic sensitivity in existing anticancer therapies, including radiotherapy, chemotherapy and immunotherapy. Consequently, we undertook this review to improve the understanding of signaling pathways influenced by lncRNAs in glioma and how lncRNAs affect therapeutic resistance.

Current Study of RhoA and Associated Signaling Pathways in Gastric Cancer

2020 ◽  
Vol 15 (7) ◽  
pp. 607-613 ◽  
Author(s):  
Haiping Liu ◽  
Yiqian Liu ◽  
Xiaochuan Zhang ◽  
Xiaodong Wang
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Actin Polymerization ◽  
Cell Transformation ◽  
Cell Movement ◽  
Invasion And Metastasis ◽  
Common Cancer

Gastric cancer (GC) is the fourth-most common cancer in the world, with an estimated 1.034 million new cases in 2015, and the third-highest cause of cancer deaths, estimated at 785,558, in 2014. Early diagnosis and treatment greatly affect the survival rate in patients with GC: the 5‐year survival rate of early GC reaches 90%‐95%, while the mortality rate significantly increases if GC develops to the late stage. Recently, studies for the role of RhoA in the diseases have become a hot topic, especially in the development of tumors. A study found that RhoA can regulate actin polymerization, cell adhesion, motor-myosin, cell transformation, and the ability to participate in the activities of cell movement, proliferation, migration, which are closely related to the invasion and metastasis of tumor cells. However, the specific role of RhoA in tumor cells remains to be studied. Therefore, our current study aimed to briefly review the role of RhoA in GC, especially for its associated signaling pathways involved in the GC progression.

scholarly journals Molecular Pathogenesis of Hodgkin Lymphoma: Past, Present, Future

2020 ◽  
Vol 21 (18) ◽  
pp. 6623 ◽  
Author(s):  
Marc Bienz ◽  
Salima Ramdani ◽  
Hans Knecht
Keyword(s):  
Immune System ◽  
Targeted Therapy ◽  
Signaling Pathways ◽  
Hodgkin Lymphoma ◽  
Genetic Instability ◽  
Host Immune System ◽  
Cellular Interactions ◽  
Classical Hodgkin Lymphoma ◽  
The Past

Our understanding of the tumorigenesis of classical Hodgkin lymphoma (cHL) and the formation of Reed–Sternberg cells (RS-cells) has evolved drastically in the last decades. More recently, a better characterization of the signaling pathways and the cellular interactions at play have paved the way for new targeted therapy in the hopes of improving outcomes. However, important gaps in knowledge remain that may hold the key for significant changes of paradigm in this lymphoma. Here, we discuss the past, present, and future of cHL, and review in detail the more recent discoveries pertaining to genetic instability, anti-apoptotic signaling pathways, the tumoral microenvironment, and host-immune system evasion in cHL.

scholarly journals Loss of cIAP1 in Endothelial Cells Limits Metastatic Extravasation through Tumor-Derived Lymphotoxin Alpha

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 599
Author(s):  
Lazaros Vasilikos ◽  
Kay Hänggi ◽  
Lisanne M. Spilgies ◽  
Samanta Kisele ◽  
Stefanie Rufli ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Advanced Disease ◽  
Disease Stage ◽  
Stromal Compartment ◽  
Tumor Load ◽  
Smac Mimetics ◽  
Advanced Disease Stage ◽  
Lymphotoxin Alpha ◽  
Open Question

In this study, we determined whether Smac mimetics play a role in metastasis, specifically in circulation, tumor extravasation and growth in a metastatic site. Reports suggest inducing the degradation of IAPs through use of Smac mimetics, alters the ability of the tumor cell to metastasize. However, a role for the immune or stromal compartment in affecting the ability of tumor cells to metastasize upon loss of IAPs has not been defined. To address this open question, we utilized syngeneic tumor models in a late-stage model of metastasis. Loss of cIAP1 in the endothelial compartment, rather than depletion of cIAP2 or absence of cIAP1 in the hematopoietic compartment, caused reduction of tumor load in the lung. Our results underline the involvement of the endothelium in hindering tumor cell extravasation upon loss of cIAP1, in contrast to the immune compartment. Endothelial specific depletion of cIAP1 did not lead to cell death but resulted in an unresponsive endothelium barrier to permeability factors causing a decrease in tumor cell extravasation. Surprisingly, lymphotoxin alpha (LTA), and not TNF, secreted by the tumor cells, was critical for the extravasation. Using TCGA, we found high LTA mRNA expression correlated with decreased survival in kidney carcinoma and associated with advanced disease stage. Our data suggest that Smac mimetics, targeting cIAP1/2, reduce metastasis to the lung by inhibiting tumor cell extravasation.

scholarly journals Molecular biology of Hodgkin lymphoma

Leukemia ◽  
2021 ◽  
Vol 35 (4) ◽  
pp. 968-981
Author(s):  
Marc A. Weniger ◽  
Ralf Küppers
Keyword(s):  
B Cells ◽  
B Cell ◽  
Signaling Pathways ◽  
Hodgkin Lymphoma ◽  
Tumor Cells ◽  
Bacterial Antigen ◽  
Cellular Interactions ◽  
Constitutive Activation ◽  
Expression Program ◽  
Hodgkin Cells

AbstractClassical Hodgkin lymphoma (cHL) is unique among lymphoid malignancies in several key biological features. (i) The Hodgkin and Reed-Sternberg (HRS) tumor cells are rare among an extensive and complex microenvironment. (ii) They derive from B cells, but have largely lost the B-cell typical gene expression program. (iii) Their specific origin appears to be pre-apoptotic germinal center (GC) B cells. (iv) They consistently develop bi- or multinucleated Reed-Sternberg cells from mononuclear Hodgkin cells. (v) They show constitutive activation of numerous signaling pathways. Recent studies have begun to uncover the basis of these specific features of cHL: HRS cells actively orchestrate their complex microenvironment and attract many distinct subsets of immune cells into the affected tissues, to support their survival and proliferation, and to create an immunosuppressive environment. Reed-Sternberg cells are generated by incomplete cytokinesis and refusion of Hodgkin cells. Epstein-Barr virus (EBV) plays a major role in the rescue of crippled GC B cells from apoptosis and hence is a main player in early steps of lymphomagenesis of EBV+ cHL cases. The analysis of the landscape of genetic lesions in HRS cells so far did not reveal any highly recurrent HRS cell-specific lesions, but major roles of genetic lesions in members of the NF-κB and JAK/STAT pathways and of factors of immune evasion. It is perhaps the combination of the genetic lesions and the peculiar cellular origin of HRS cells that are disease defining. A combination of such genetic lesions and multiple cellular interactions with cells in the microenvironment causes the constitutive activation of many signaling pathways, often interacting in complex fashions. In nodular lymphocyte predominant Hodgkin lymphoma, the GC B cell-derived tumor cells have largely retained their typical GC B-cell expression program and follicular microenvironment. For IgD-positive cases, bacterial antigen triggering has recently been implicated in early stages of its pathogenesis.

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