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.

The impact of c-Met inhibition on molecular features and metastatic potential of melanoma cells.

The aberrant activation of the hepatocyte growth factor receptor (c-Met) in malignant melanoma is associated with poor prognosis, fostering tumor progression, angiogenesis, and invasiveness. While therapeutic targeting of this pathway has shown promise in several tumors, our previous findings revealed increased tumorigenicity following tyrosine kinase inhibitor SU11274 treatment. Therefore, we hypothesized that administering c-Met inhibitors may elicit distinct effects in human melanoma cells.

CDH1 methylation analysis in invasive lobular breast carcinomas with and without gene mutation.

The proposed role of CDH1 (E-cadherin gene) methylation as a mechanism of gene inactivation in invasive lobular carcinoma (ILC) remains inconclusive. For many years, CDH1 promoter hypermethylation has been regarded as a mechanism for gene inactivation in ILC. However, this assumption has primarily relied on non-quantitative assays, which have reported CDH1 methylation frequencies ranging from 26 to 93% at CpG sites within the island region.

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.

DNA damage levels in peripheral blood mononuclear cells before and after first cycle of chemotherapy have comparable prognostic values in germ cell tumor patients.

Background: Germ cell tumors (GCTs) represent the most frequent solid malignancy in young men. This malignancy is highly curable by cisplatin (CDDP)-based chemotherapy. However, there is a proportion of patients having a poor prognosis due to refractory disease or its relapse.

Epiphytic microflora and mycotoxin content in meadows-Is plant biodiversity affecting fungal contamination?

Ecosystem services are an important aspect of grasslands utilization; however, they are often contradictory to their main purpose, which is a production of good quality and safe feed. In this study, we evaluated the difference between grass monocultures and species-rich mixtures in terms of epiphytic microflora and mycotoxin contamination levels. We hypothesized that higher species diversity would lead to higher microbial counts, which could lead to higher mycotoxin contamination risk.

Iron oxide nanoparticles trigger endoplasmic reticulum damage in steatotic hepatic cells.

Iron oxide nanoparticles (IONPs) are being actively researched in various biomedical applications, particularly as magnetic resonance imaging (MRI) contrast agents for diagnosing various liver pathologies like nonalcoholic fatty liver diseases, nonalcoholic steatohepatitis, and cirrhosis. Emerging evidence suggests that IONPs may exacerbate hepatic steatosis and liver injury in susceptible livers such as those with nonalcoholic fatty liver disease. However, our understanding of how IONPs may affect steatotic cells at the sub-cellular level is still fragmented.

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.

Liquid Biopsy in Gastrointestinal Cancers: How Close Are We to Reaching the Clinic?

Gastrointestinal (GI) cancers are malignancies that develop within the digestive system and account for one in four cancer cases according to WHO data [...

Lysosomal nanotoxicity: Impact of nanomedicines on lysosomal function.

Although several nanomedicines got clinical approval over the past two decades, the clinical translation rate is relatively small so far. There are many post-surveillance withdrawals of nanomedicines caused by various safety issues. For successful clinical advancement of nanotechnology, it is of unmet need to realize cellular and molecular foundation of nanotoxicity.

Mechanical Regulation of Mitochondrial Dynamics and Function in a 3D-Engineered Liver Tumor Microenvironment.

It has become evident that physical stimuli of the cellular microenvironment transmit mechanical cues regulating key cellular functions, such as proliferation, migration, and malignant transformation. Accumulating evidence suggests that tumor cells face variable mechanical stimuli that may induce metabolic rewiring of tumor cells. However, the knowledge of how tumor cells adapt metabolism to external mechanical cues is still limited.

Nutraceuticals as Supportive Therapeutic Agents in Diabetes and Pancreatic Ductal Adenocarcinoma: A Systematic Review.

The correlation between pancreatic ductal adenocarcinoma (PDAC) and diabetes-related mechanisms support the hypothesis that early therapeutic strategies targeting diabetes can contribute to PDAC risk reduction and treatment improvement. A systematic review was conducted, using PubMed, Embase and Cochrane Library databases, to evaluate the current evidence from clinical studies qualitatively examining the efficacy of four natural products: Curcumin- L.; Thymoquinone- L.

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.

The Metastatic Process through the Eyes of Epigenetic Regulation: A Promising Horizon for Cancer Therapy.

Genetic aberrations, including chromosomal rearrangements, loss or amplification of DNA, and point mutations, are major elements of cancer development [...

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.

The interactions between DNA nanostructures and cells: A critical overview from a cell biology perspective.

DNA nanotechnology has yielded remarkable advances in  composite materials with diverse applications in biomedicine. The specificity and predictability of building 3D structures at the nanometer scale make DNA nanotechnology a promising tool for uses in biosensing, drug delivery, cell modulation, and bioimaging. However, for successful translation of DNA nanostructures to real-world applications, it is crucial to understand how they interact with living cells, and the consequences of such interactions.

A pooled analysis of molecular epidemiological studies on modulation of DNA repair by host factors.

Levels of DNA damage represent the dynamics between damage formation and removal. Therefore, to better interpret human biomonitoring studies with DNA damage endpoints, an individual's ability to recognize and properly remove DNA damage should be characterized. Relatively few studies have included DNA repair as a biomarker and therefore, assembling and analyzing a pooled database of studies with data on base excision repair (BER) was one of the goals of hCOMET (EU-COST CA15132).

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).