CES1 (Carboxylesterase 1)

This strategy is rapid, sensitive, and highly selective, enabling accurate measurement in complex matrices. It provides a novel approach for early warning of liver injury and HCC and for exploring the biological significance of glycosylated CEs1.

LXRα knockout (LXRα-/-) mice exhibited aggravated HFD-induced steatosis and impaired metabolic conversion of the CES1/CES2 substrates, oseltamivir and irinotecan. Silencing of CES1 or CES2 abolished ORI's lipid-lowering effect, confirming their essential roles. These findings establish the LXRα-CES1/CES2 pathway as a pivotal node integrating hepatic lipid homeostasis and drug metabolism, positioning ORI as a promising therapeutic agent for MASLD.

In vitro, niraparib lacks any CYP inhibition, induces CYP1A2 but not CYP3A4, and is not a CYP substrate, unlike some other PARPi's, which inhibit and induce numerous enzymes/transporters and are objects of CYP metabolism. At clinically relevant doses of niraparib ≥ 200 mg, a weak induction risk is predicted with sensitive CYP1A2 substrates, such as caffeine, and both niraparib and olaparib clinically increase serum creatinine in cancer patients, with up to a moderate inhibition risk predicted with MATE-1/-2K substrates, such as metformin, using a PBPK model of niraparib in the absence of a dedicated DDI study.

Felodipine and GSK2033 treatment eliminated the differential effects on TG concentration between wild-type and Ces1d-deficient hepatocytes. The results suggest that CES1/Ces1d activates PPARγ, LXR and SREBP1c pathways, thereby increasing TG synthesis and LD storage by augmenting fatty acid esterification.

This study establishes a non-viral, transient gene delivery platform using autologous WJ-MSCs for dual-action gene therapy in lung cancer brain metastases. The combined use of CES1 and sTRAIL and enables precise tumor targeting and drug activation, offering a promising avenue for personalized, stem cell-based treatment strategies to improve outcomes in patients with brain metastatic lung cancer.

Moreover, CES1 influenced the proportion of nine types of tumor-infiltrating immune cells (TICs), particularly M2 macrophages, as supported by functional studies involving CES1 knockdown and overexpression in AML cells and AML xenograft tumor models. Hypercholesterolemia and CES1 can promote CNS relapse in AML patients, particularly through CES1's potential role in modulating immune infiltration within the TME.

This study has found significant variability in the expression of CAP metabolic enzymes across individuals and tissues. Developing a treatment flowchart based on metabolic enzymes provides a foundation for personalized HCC treatment and enhances the effectiveness of CAP therapy.

Inhibition of PPARG abrogated the anti-growth and anti-metastasis functions of CES1 in breast cancer cells. This study elucidates that CES1 inhibits the malignant progression of breast cancer by up-regulating the expression of PPARG.

A role of CES1 expression in skin is demonstrated for the first time. Our study suggests that 2-AG degradation to arachidonate favors melanoma progression, either reflecting the carcinogenic role of ARA or that monoacylglycerols like 2-AG and/or other CES1 substrates may exert antitumor effects, indicating that CES1 could be a potential therapeutic target. CES1 expression and high SAG, 2-AG, and ARA levels may be a signature of specific BRAF-driven malignant melanoma subtypes which are associated with discrete metabolic adaptations.

P=N/A, N=80, Recruiting, Ain Shams University

Subsequently, we performed in vitro studies by HNSCC-PDO and SCC-9 and found that CES1-overexpressing cells exhibited reduced sensitivity to cisplatin and stronger tumor malignant biological behavior compared with CES1-knockdown cells. The observed association between CES1 expression and tobacco smoking implies a potential influence of smoking on the efficacy of cisplatin-based chemotherapy in HNSCC through the regulation of CES1 expression.

The ratiometric SERS probe strategy, in which a ratio response is employed, permits sensitive and reproducible SERS detection by facilitating intrinsic calibration to rectify signal fluctuations resulting from temporal and spatial variations in the detection conditions. Concurrently, the implementation of Raman-silent region reporter molecules mitigates the interference from endogenous biomolecules in SERS measurements and offers a novel approach for achieving highly sensitive and interference-free detection of intracellular hCE1.