Early Detection and Investigation of Extracellular Vesicles Biomarkers in Breast Cancer

Breast cancer (BC) is the most commonly diagnosed malignant tumor in women worldwide, and the leading cause of cancer death in the female population. The percentage of patients experiencing poor prognosis along with the risk of developing metastasis remains high, also affecting the resistance to current main therapies. Cancer progression and metastatic development are no longer due entirely to their intrinsic characteristics, but also regulated by signals derived from cells of the tumor microenvironment. Extracellular vesicles (EVs) packed with DNA, RNA, and proteins, are the most attractive targets for both diagnostic and therapeutic applications, and represent a decisive challenge as liquid biopsy-based markers. Here we performed a study based on a multiplexed phenotyping flow cytometric approach to characterize BC-derived EVs from BC patients and cell lines, through the detection of multiple antigens. Our data reveal the expression of EVs-related biomarkers derived from BC patient plasma and cell line supernatants, suggesting that EVs could be exploited for characterizing and monitoring disease progression.

Methylation of MMP2 and MMP9 in patients with localized and generalized forms of Ewing's sarcoma.

e23503 Background: MMPs play a critical role in tumor growth and progression, metastatic development, angiogenesis, and tumor invasion. Epigenetic regulation of MMP2 and MMP9 levels is often disrupted in cancer and is considered as potential biomarkers. In this study, we tried to assess the methylation of the MMP2 and MMP9 genes in patients with localized and generalized forms of Ewing's sarcoma (ES). Methods: As a material used DNA from FFPE of primary tumor of 20 patients with localized forms ES and 20 patients with generalized forms ES. After bisulfite conversion of total DNA and PCR, the level of CpG methylation was assessed by sequencing on a Genetic Analyzer Applied Biosystems 3500. Results: The analysis showed the presence of hypomethylation of the MMP2 in the group with generalized forms (100%) 1.25 times more often than in the group with localized forms (80%), and hypermethylation was observed only in the group with localized forms–20% of cases (χ2 = 4.234, p = 0.040). On the other hand, hypermethylation was 1.9 times more common in the group with localized forms of ES (90%) (χ2 = 8.313, p = 0.004). Differences in the methylation status of the MMP2 and MMP9 indicate that the presence of hypomethylation at two loci increases the risk of developing generalized ES by 22 times (OR = 22.2, p < 0.05; CI95% 2.460-20.769). Conclusions: Specific methylation of the matrix metalloproteinases genes MMP2 and MMP9 identified in the groups of localized and generalized Ewing's sarcoma. At the same time, the group with generalized forms of ES was characterized by gene hypomethylation.

When a House Is Not a Home: A Survey of Antimetastatic Niches and Potential Mechanisms of Disseminated Tumor Cell Suppression

Over the last four decades, the cancer biology field has concentrated on cellular and microenvironmental drivers of metastasis. Despite this focus, mortality rates upon diagnosis of metastatic disease remain essentially unchanged. Would a small change in perspective help? Knowing what constitutes an inhospitable, rather than hospitable, microenvironment could provide the inspiration necessary to develop better therapies and preventative strategies. In this review, we canvas the literature for hints about what characteristics three common antimetastatic niches—skeletal muscle, thyroid, and spleen—have in common. We posit that thorough molecular and mechanistic characterization of antimetastatic tissues may inspire reimagined therapies that inhibit metastatic development and/or progression in an enduring manner. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 16 is January 25, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

DESCRIPTIVE ANALYSIS OF PRIMARY BREAST TUMORS CHARACTERISTICS IN PATIENTS WITH BONE METASTASIS

Breast cancer is a severe disease with high morbidity and mortality affecting both women and men from all around the world. When it does not get diagnosed in early stages it metastasizes to other organs and tissues, thus becoming incurable. In addition, between 25-50% of patients will suffer from a metastatic development after the initial treatment. The most common locations are the bones, the liver, the lungs and the nervous system. The current research is an analysis of the molecular, macroscopic and microscopic characteristics of tumors in a cohort of 67 female patients with bone metastases from an initial breast neoplasm.

PTM AND CELL CYCLE GATING MECHANISMS DEVIATED FOR PROGRESSION OF CANCER

Post translational modifications like phosphorylation, Glycosylation and ADP ribosylation serves as biomarkers and are mainly involved in regulation of signalling pathways, cell polarity and cell cycle progression. So, this review helps in finding the biomarkers in understanding of cancer genome and also the deviations observed in gating mechanisms. Mucin 3 is mainly involved in EMT transition and Phosphorylation is also required for effective complex formation between catenin and cadherin. Hyaluron acts as medium for the tumors cells and aids in their movement and responsible for metastatic development. Epigenetic modification like methylation is helpful for cancerous genome to develop additional mutations for survival of the genome. Key words: Cyclin D, PTMs, Gating, Glycosylation, Phosphorylation.