Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor and is associated with a poor clinical prognosis. Despite the progress in the understanding of the molecular and genetic changes that promote tumorigenesis, effective treatment options are limited. The present review intended to identify and summarize major signaling pathways and genetic abnormalities involved in the pathogenesis of GBM, as well as therapies that target these pathways. Glioblastoma remains a difficult to treat tumor; however, in the last two decades, significant improvements in the understanding of GBM biology have enabled advances in available therapeutics. Significant genomic events and signaling pathway disruptions (NF-κB, Wnt, PI3K/AKT/mTOR) involved in the formation of GBM were discussed. Current therapeutic options may only marginally prolong survival and the current standard of therapy cures only a small fraction of patients. As a result, there is an unmet requirement for further study into the processes of glioblastoma pathogenesis and the discovery of novel therapeutic targets in novel signaling pathways implicated in the evolution of glioblastoma.
Introduction. Ovarian cancer is characterized by complex diagnostics and flow forecasting, which makes it important to search for prognostic criteria. However, the prognostic significance of some factors has not yet been studied.The purpose of the study: to identify the features of immune response in the localization of metastases in the large omentum in ovarian cancer.Tasks: to reveal the pathomorphological features of the cellular immune response to metastases in the large omentum in patients with ovarian cancer II–III stages; to conduct histomorphometry of elements of the immune system in the area of metastases.Material and methods. The study was carried out on the biomaterial of the large omentum of 94 women with ovarian cancer II–III stage. The measurements were carried out on paraffin sections stained with hematoxylin and eosin and included evaluation of the following parameters: the number of lymphocytes in the field of view at the border and away from the tumor, the continuity of the lymphocyte shaft at the border with the tumor, the number of neutrophils on the border with the tumor, the presence of plasmocytes on the border with tumor. The preparations were studied and photographed under a microscope with a microscope-microvision mVizo-103 and a microscope Micromed 3.The results. Observed 94 patients with stage II–III ovarian cancer. Over the three-year follow-up period, the disease-free survival rate was 79.8%. A total of 64 patients with stage III disease were observed. A recurrence-free survival rate among patients with stage III ovarian cancer was 74.32%. Without relapse during the follow-up period, those patients were found whose lymphocytes formed a continuous shaft at the border with the tumor, their number in the field of view ×200 was 400 or more, the plasmocytes were present in the composition of the shaft, and the neutrophils were absent or few.The conclusion. A detailed histological study to quantify and qualitatively determine the severity of lymphoid elements of the large omentum allowed an indirect assessment of the state of the immune system and the probability of an unfavorable outcome in patients with ovarian neoplasia.
The review summarizes current information about the role and significance of adhesion molecules in the process of tumor metastasis. For example, different tumors is shown that changes in the expression of adhesion molecules leads to disruption of the regulatory interactions in the processes of proliferation, cytodifferentiation and migration of tumor cells, enables the cascade of pathological processes leading to the colonization of other tumor cells remote from the tumor bodies. The phenomenology of tumor development and metastasis is shown. The participation of the main groups of adhesion molecules (cadherins, integrins, selectins, immunoglobulins and white blood cell homing receptors) at the stages of metastasis is considered. A violation of cadherin expression is accompanied by a decrease in the expression of integrins involved in the formation of hemidesmosomes, while a cascade of reactions develops that contributes to the development of an aggressive malignant phenotype, cells acquire an increased ability to migrate and invade, resulting in the appearance of a tumor in secondary foci. The role of immunoglobulins in the development of metastatic process has been studied in less detail than in cadherins and integrins. It was found that immunoglobulins are involved in the formation of resistance of tumor cells to proapoptotic signals. Immunoglobulins increase the expression of metalloproteinase genes involved in the degradation of the extracellular matrix, which is a factor in the initiation of metastasis. A correlation between increased selectin expression and increased metastasis is shown. An increase in the expression level of white blood cell homing receptors leads to an increase in the invasive potential of tumors. The results of the study of cell adhesion proteins serve as a fundamental basis for the development of methods of antitumor therapy. Over the past decades, a number of immunohistochemical protein detection reactions have become one of the diagnostic methods of cancer clinics. However, the role of cell adhesion molecules in ensuring the metastasis process, as well as their significance in the prognosis of the development of the tumor process and antitumor therapy, needs to be further studied.
The greater omentum is an organ in which metastases of malignant neoplasms of the female reproductive system are often formed. The issues of adaptive and reactive transformations of the greater omentum under conditions of a tumor process in the organs of the female reproductive system have been insufficiently studied. The aim of the study was to elucidate morphological and functional ultrastructural and immune-histochemical changes in the greater omentum in women with ovarian tumor lesions. Using the methods of light and electron microscopy, immunohistochemistry and morphometry, the ovaries of 48 women were examined, who were diagnosed with poorly differentiated serous-papillary adenocarcinoma stage II (20 patients, group 1), stage III (28 patients, group 2). In stage III patients, numerous tumor metastases were detected in the greater omentum. The results of the study showed that in the patients of the 2nd group, in the peri-tumor areas of the greater omentum, the vessels of the microvasculature were dilated, in the connective tissue, moderate edema and leukocyte infiltration were observed. Immuno-histochemical markers showed an increase in the number of immunocompetent cells, mainly T-lymphocytes in the tumor and in the peri-tumor areas. In the tumor and in the surrounding areas of the greater omentum, the process of neoplasm of blood capillaries was noted, differences in the density of collagen fibrils in different parts of the serous membrane were revealed, and the presence of numerous holes was shown, the sizes of which were reduced in areas with metastases. The results obtained show the adaptive and reparative capabilities of the structures of the greater omentum during the tumor process in the organs of the female reproductive system, indicate the important role of the greater omentum in providing protective reactions in the abdominal cavity. In response to the invasion of tumor cells, the processes of angiogenesis are activated in the greater omentum, and the number of immunocompetent cells increases in neo-lymphogenesis. The materials of the study indicate a significant plasticity and reactivity of the greater omentum under conditions of a tumor process in the body. However, the presence of a pronounced proliferative activity of tumor cells in tumor metastases indicates that these adaptive capacities are insufficient to resist tumor invasion into the greater omentum.
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