Agapi Kataki

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is now recognized as the leading cause of chronic liver disease worldwide. MASLD spans a spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and is linked to progressive fibrosis and ultimately hepatocellular carcinoma (HCC). Growing evidence implicates cellular senescence (CS) and lipid droplets (LDs) as key drivers of disease progression, although their interaction remains poorly characterized. This review provides an integrative and stage-dependent synthesis of current mechanistic insights into how bidirectional crosstalk between CS and LD regulation shapes the transition from steatosis to MASH. Senescent hepatocytes display altered lipid metabolism, including upregulation of receptors such as cluster of differentiation (CD) 36, enhancing lipid uptake to meet increased energy demands. Initially, elevated free fatty acid influx can activate peroxisome-proliferator-activated receptor alpha (PPARα), promoting fatty acid oxidation (FAO) as a compensatory response. Over time, persistent CS under steatotic conditions leads to mitochondrial dysfunction and suppression of fatty acid oxidation (FAO), while the senescence-associated secretory phenotype (SASP), largely driven by nuclear factor—kappa B (NF-κB) signaling, promotes chronic hepatic inflammation. By framing LDs as active modulators of senescence-associated signaling rather than passive lipid stores, this review highlights how disruption of senescence–lipid feedback loops may represent a disease-modifying opportunity in MASLD progression.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is now recognized as the leading cause of chronic liver disease worldwide. MASLD spans a spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), and is linked to progressive fibrosis and ultimately hepatocellular carcinoma (HCC). Growing evidence implicates cellular senescence (CS) and lipid droplets (LD) dysregulation as key drivers of disease progression, although their interaction remains poorly characterized. This review synthe-sizes current mechanistic insights into how CS and LD regulation affect the transition from steatosis to MASH. Senescent hepatocytes display altered lipid metabolism, includ-ing upregulation of receptors such as cluster of differentiation (CD) 36, enhancing lipid uptake to meet increased energy demands. Initially, elevated free fatty acid influx can ac-tivate peroxisome-proliferator receptor alpha (PPARα), promoting fatty acid oxidation (FAO) as a compensatory response. Over time, persistent cellular senescence (CS) under steatotic conditions leads to mitochondrial dysfunction and suppression of fatty acid ox-idation (FAO), while the senescence-associated secretory phenotype (SASP), largely driven by nuclear factor – kappa B (NF-κB) signaling, promotes chronic hepatic inflammation. A comprehensive understanding of this dynamic crosstalk between CS and lipid metabo-lism could identify novel therapeutic targets to modulate the MASLD progression.

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

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

Neuroendocrine neoplasms (NEN) represent a rare heterogeneous group with an increasing incidence, consisting of neuroendocrine tumours...

Previous studies have reported that CD44 variant 6 (CD44v6) and metastasis‑associated protein 1 (MTA1) are contributing factors to cancer progression. The present study aimed to evaluate the expression profiles for associations with patients' demographic data, clinicopathological characteristics, the presence of partial epithelial‑to‑mesenchymal transition (pEMT), metastatic potential based on the presence of CK20⁺ CEA⁺ CXCR4⁺ circulating tumor cells (CTCs) and prognosis (median follow‑up, 45 months). Thus, frozen tissue samples from 31 patients with stage I‑III colorectal cancer (CRC), 15 benign colorectal polyps and seven normal colorectal tissues were analyzed to detect membranous (m)CD44v6 and MTA1 expression via flow cytometry. The results demonstrated that the mCD44v6 and MTA1 expression profiles were significantly correlated (r_s=+0.786, P<0.001). Notably, MTA1 expression was not associated with any of the clinicopathological characteristics assessed. The percentage of mCD44v6‑positive cells within tumors was higher in the right‑sided cancer lesions (P=0.014), suggesting that proximal and distal CRCs are distinct clinicopathological entities. Furthermore, downregulated mCD44v6 expression was significantly associated with the presence of CTCs (P=0.017). This association was stronger for pEMT (co‑expression of N‑ and E‑cadherin mRNAs) primary lesions (P=0.009). In addition, patients with CRC with low levels of mCD44v6 had unfavorable survival outcomes (P=0.037). Taken together, these results suggest that targeted analysis of membranous CD44v6 as opposed to membranous‑cytoplasmic expression is important in determining the prognosis of patients with CRC. Furthermore, downregulated mCD44v6 expression in malignancies presenting CTCs reinforces the importance of tumor‑stroma reciprocal influence during the metastatic process and encourages the assessment of relevant therapeutic strategies.

Cell senescence constitutes a physiological process that serves as protection from malignant transformation of cells. However, recent scientific discoveries also identify cell senescence as pivotal in hepatocellular cancer (HCC) biology. The review herein aimed to accumulate evidence on senescence as a mediator of HCC occurrence in hepatitis B (HBV), C (HCV) virus infections, and non-alcoholic fatty liver disease (NAFLD). In HBV infection, the carcinogenic HBV X protein frequently mutates during chronic infection, and subsequently exhibits different effects on senescence. In HCV infection, senescent non-functional T-cells do not effectively clear pre-malignant hepatocytes. Furthermore, the HCV Core protein inhibits the occurrence of normal stress-induced hepatocyte senescence, allowing damaged cells to maintain their proliferative potential. In NAFLD-mediated HCC, current data point towards the gut microbiome and hepatic stellate cell senescence. Additionally, senescence contributes in the development of resistance in targeted therapies, such as sorafenib. Finally, the promising role of senotherapeutics in HCC was also explored. Overall, although we may still be at a primitive stage in fully unraveling the role of senescence in cancer, it seems that understanding and harnessing senescence may have the potential to revolutionize the way we treat hepatocellular cancer.