Leveraging Epigenetic Alterations in Pancreatic Ductal Adenocarcinoma for Clinical Applications.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by late detection and poor prognosis. Recent research highlights the pivotal role of epigenetic alter- ations in driving PDAC development and progression. These changes, in conjunction with genetic mutations, contribute to the intricate molecular landscape of the disease.

Epigenetic deregulation in breast cancer microenvironment: Implications for tumor progression and therapeutic strategies.

Breast cancer comprises a substantial proportion of cancer diagnoses in women and is a primary cause of cancer-related mortality. While hormone-responsive cases generally have a favorable prognosis, the aggressive nature of triple-negative breast cancer presents challenges, with intrinsic resistance to established treatments being a persistent issue. The complexity intensifies with the emergence of acquired resistance, further complicating the management of breast cancer.

Nanomedicine and epigenetics: New alliances to increase the odds in pancreatic cancer survival.

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers worldwide, primarily due to its robust desmoplastic stroma and immunosuppressive tumor microenvironment (TME), which facilitate tumor progression and metastasis. In addition, fibrous tissue leads to sparse vasculature, high interstitial fluid pressure, and hypoxia, thereby hindering effective systemic drug delivery and immune cell infiltration. Thus, remodeling the TME to enhance tumor perfusion, increase drug retention, and reverse immunosuppression has become a key therapeutic strategy.

Genotoxic effects of occupational exposure to glass fibres - A human biomonitoring study.

As part of a large human biomonitoring study, we conducted occupational monitoring in a glass fibre factory in Slovakia. Shopfloor workers (n = 80), with a matched group of administrators in the same factory (n = 36), were monitored for exposure to glass fibres and to polycyclic aromatic hydrocarbons (PAHs). The impact of occupational exposure on chromosomal aberrations, DNA damage and DNA repair, immunomodulatory markers, and the role of nutritional and lifestyle factors, as well as the effect of polymorphisms in metabolic and DNA repair genes on genetic stability, were investigated.

Liquid biopsy and preclinical tools for advancing diagnosis and treatment of patients with pancreatic neuroendocrine neoplasms.

Pancreatic neuroendocrine neoplasms (pNENs) are rare cancers with broad challenges for their management. The main clinical obstacles are the high rate of patients diagnosed at advanced stages, lack of prognostic markers for early detection of disease recurrence in resected patients, significant limitations in identifying those who will benefit from adjuvant therapy, and timely recognition of treatment response. Therefore, the discovery of new prognostic and predictive markers is necessary for patient stratification and clinical management.

Decitabine potentiates efficacy of doxorubicin in a preclinical trastuzumab-resistant HER2-positive breast cancer models.

Acquired drug resistance and metastasis in breast cancer (BC) are coupled with epigenetic deregulation of gene expression. Epigenetic drugs, aiming to reverse these aberrant transcriptional patterns and sensitize cancer cells to other therapies, provide a new treatment strategy for drug-resistant tumors. Here we investigated the ability of DNA methyltransferase (DNMT) inhibitor decitabine (DAC) to increase the sensitivity of BC cells to anthracycline antibiotic doxorubicin (DOX).

Monosomy 3 Influences Epithelial-Mesenchymal Transition Gene Expression in Uveal Melanoma Patients; Consequences for Liquid Biopsy.

Despite outstanding advances in diagnosis and the treatment of primary uveal melanoma (UM), nearly 50% of UM patients develop metastases via hematogenous dissemination, driven by the epithelial-mesenchymal transition (EMT). Despite the failure in UM to date, a liquid biopsy may offer a feasible non-invasive approach for monitoring metastatic disease progression and addressing protracted dormancy. To detect circulating tumor cells (CTCs) in UM patients, we evaluated the mRNA expression of EMT-associated transcription factors in CD45-depleted blood fraction, using qRT-PCR.

Epigenetics in Breast Cancer Therapy-New Strategies and Future Nanomedicine Perspectives.

Epigenetic dysregulation has been recognized as a critical factor contributing to the development of resistance against standard chemotherapy and to breast cancer progression via epithelial-to-mesenchymal transition. Although the efficacy of the first-generation epigenetic drugs (epi-drugs) in solid tumor management has been disappointing, there is an increasing body of evidence showing that epigenome modulation, in synergy with other therapeutic approaches, could play an important role in cancer treatment, reversing acquired therapy resistance. However, the epigenetic therapy of solid malignancies is not straightforward.

Disulfiram Overcomes Cisplatin Resistance in Human Embryonal Carcinoma Cells.

Cisplatin resistance in testicular germ cell tumors (TGCTs) is a clinical challenge. We investigated the underlying mechanisms associated with cancer stem cell (CSC) markers and modalities circumventing the chemoresistance. Chemoresistant models (designated as CisR) of human embryonal carcinoma cell lines NTERA-2 and NCCIT were derived and characterized using flow cytometry, gene expression, functional and protein arrays.

A disintegrin and metalloprotease 23 hypermethylation predicts decreased disease-free survival in low-risk breast cancer patients.

A Disintegrin And Metalloprotease 23 (ADAM23), a member of the ADAM family, is involved in neuronal differentiation and cancer. ADAM23 is considered a possible tumor suppressor gene and is frequently downregulated in various types of malignancies. Its epigenetic silencing through promoter hypermethylation was observed in breast cancer (BC).

Impact of interleukin 13 (IL13) genetic polymorphism Arg130Gln on total serum immunoglobulin (IgE) levels and interferon (IFN)-γ gene expression.

This cross-sectional study was designed to investigate the extent of genetic susceptibility by targeting variants in interleukin (IL)-4/IL-13 signalling pathways leading to atopic disease in early childhood. We evaluated involvement of five single nucleotide polymorphisms IL4 C-590T, IL13 C-1055T, IL13 Arg130Gln, IL4RA Ile50Val and IL4RA Gln576Arg, in the control of serum total and antigen-specific immunoglobulin (Ig)E levels. Furthermore, we analysed their association with changes in gene expression of five cytokines having key roles in inflammatory and anti-inflammatory immune response [IL-4, IL-13, interferon (IFN)-γ, IL-8 and IL-10].

Genetic determinants of quantitative traits associated with cardiovascular disease risk.

Established risk factors for cardiovascular diseases (CVD) may be moderated by genetic variants. In 2403 unrelated individuals from general practice (mean age 40.5 years), we evaluated the influence of 15 variants in 12 candidate genes on quantitative traits (QT) associated with CVD (body mass index, abdominal obesity, glucose, serum lipids, and blood pressure).