Despite the superior efficacy of radiotherapy in esophageal squamous cell carcinoma (ESCC), radioresistance by cancer stem cells (CSCs) leads to recurrence, metastasis, and treatment failure. Therefore, it is necessary to develop CSC-based therapies to enhance radiotherapy. miR-339-5p (miR339) is involved in stem cell division and DNA damage checkpoint signaling pathways based on ESCC cohort.
View Article and Find Full Text PDFPurpose: Simultaneous profiling of cell-free DNA (cfDNA) methylation and fragmentation features to improve the performance of cfDNA-based cancer detection is technically challenging. We developed a method to comprehensively analyze multimodal cfDNA genomic features for more sensitive esophageal squamous cell carcinoma (ESCC) detection.
Materials And Methods: Enzymatic conversion-mediated whole-methylome sequencing was applied to plasma cfDNA samples extracted from 168 patients with ESCC and 251 noncancer controls.
Cancer stem cells (CSCs) are essential for tumor initiation, recurrence, metastasis, and resistance. However, targeting CSCs as a therapeutic approach remains challenging. Here, a stemness signature based on 22-gene is developed to predict prognosis in esophageal squamous cell carcinoma (ESCC).
View Article and Find Full Text PDFRadiotherapy, a widely used therapeutic strategy for esophageal squamous cell carcinoma (ESCC), is always limited by radioresistance of tumor tissues and side-effects on normal tissues. Herein, a signature based on four core genes of cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, is developed to predict prognosis and assess immune cell infiltration, indicating that the cGAS-STING pathway and radiotherapy efficacy are closely intertwined in ESCC. A novel lipid-modified manganese diselenide nanoparticle (MnSe-lipid) with extraordinarily uniform sphere morphology and tumor microenvironment (TME) responsiveness is developed to simultaneously overcome radioresistance and reduce side-effects of radiation.
View Article and Find Full Text PDFTherapy resistance and metastatic progression jointly determine the fatal outcome of cancer, therefore, elucidating their crosstalk may provide new opportunities to improve therapeutic efficacy and prevent recurrence and metastasis in esophageal squamous cell carcinoma (ESCC). Here, we have established radioresistant ESCC cells with the remarkable metastatic capacity, and identified miR-494-3p (miR494) as a radioresistant activator. Mechanistically, we demonstrated that cullin 3 (CUL3) is a direct target of miR494, which is transcriptionally regulated by JunD, and highlighted that JunD-miR494-CUL3 axis promotes radioresistance and metastasis by facilitating epithelial-mesenchymal transition (EMT) and restraining programmed cell death 1 ligand 1 (PD-L1) degradation.
View Article and Find Full Text PDFSynth Syst Biotechnol
September 2023
The ability to precisely control activities of engineered designer cells provides a novel strategy for modern precision medicine. Dynamically adjustable gene- and cell-based precision therapies are recognized as next generation medicines. However, the translation of these controllable therapeutics into clinical practice is severely hampered by the lack of safe and highly specific genetic switches controlled by triggers that are nontoxic and side-effect free.
View Article and Find Full Text PDFCirculating miRNA expression is most commonly measured by qRT-PCR, however, the lack of a suitable endogenous control hinders people from evaluating the accurate changes in miRNA expression levels and developing the non-invasive biomarkers. In this study, we aimed to screen the specific, highly stable endogenous control in esophageal squamous cell carcinoma (ESCC) to overcome the obstacle. We selected "housekeeping" miRNAs according to the published database and initially acquired 21 miRNAs.
View Article and Find Full Text PDFSurgical resection is the main treatment option for most solid tumors, yet cancer recurrence after surgical resection remains a significant challenge in cancer therapy. Recent advances in cancer immunotherapy are enabling radical cures for many tumor patients, but these technologies remain challenging to apply because of side effects related to uncontrollable immune system activation. Here, we develop far-red light-controlled immunomodulatory engineered cells (FLICs) that we load into a hydrogel scaffold, enabling the precise optogenetic control of cytokines release (IFN-β, TNF-α, and IL-12) upon illumination.
View Article and Find Full Text PDFSignal Transduct Target Ther
October 2022
Whereas it is appreciated that cancer cells rewire lipid metabolism to survive and propagate, the roles of lipid metabolism in metastasis remain largely unknown. In this study, using esophageal squamous cell carcinoma (ESCC) as a pulmonary metastasis model, we find that the enzyme fatty acid 2-hydroxylase (FA2H), which catalyzes the hydroxylation of free fatty acids (FAs), is enriched in a subpopulation of ESCC cells with high metastatic potential, and that FA2H knockdown markedly mitigates metastatic lesions. Moreover, increased FA2H expression is positively associated with poor survival in patients with ESCC.
View Article and Find Full Text PDFCurr Cancer Drug Targets
July 2022
Background: Ovarian cancer (OVCA) has unique epigenetic alterations and defects in homologous recombination (HR). Despite initial sensitivity to platinum-based chemotherapy, HR dysfunctional tumors eventually acquire drug resistance. Fanconi anemia (FA) is characterized by bone marrow failure (BMF) and a reduced ability to eradicate DNA interstrand cross-links (ICL).
View Article and Find Full Text PDFBackground: Currently, there is no clinically relevant non-invasive biomarker for early detection of esophageal squamous cell carcinoma (ESCC). Herein, we established and evaluated a circulating microRNA (miRNA)-based signature for the early detection of ESCC using a systematic genome-wide miRNA expression profiling analysis.
Methods: We performed miRNA candidate discovery using three ESCC tissue miRNA datasets (n = 108, 238, and 216) and the candidate miRNAs were confirmed in tissue specimens (n = 64) by qRT-PCR.
Radioresistance is an important challenge for clinical treatments. The main causes of radioresistance include hypoxia in the tumor microenvironment, the antioxidant system within cancer cells, and the upregulation of DNA repair proteins. Here, a multiple radiosensitization strategy of high-Z-element-based radiation enhancement is designed, attenuating hypoxia and microRNA therapy.
View Article and Find Full Text PDFThis study aims to investigate the prognostic significance of p-JNK in breast cancer patients receiving neoadjuvant chemotherapy (NACT) and analyze the relationship between anisomycin, p-JNK. A total of 104 breast cancer patients had NACT were enrolled in this study. The western blot and immunohistochemistry assays were used to determine the protein expressions of p-JNK in human breast cancer cell lines and patients' cancer tissues.
View Article and Find Full Text PDFMetastasis is still a major cause of cancer-related mortality. Lysosome-associated membrane protein 3 (LAMP3) has been implicated in the invasiveness and metastasis of multiple cancer types; however, the underlying mechanisms are unclear. In this study, we found that LAMP3 was overexpressed in esophageal squamous cell carcinoma (ESCC) tissues and that this increased expression positively correlated with lymph node metastasis.
View Article and Find Full Text PDFSwitch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complexes have a mutation rate of approximately 20% in human cancer, and is the most frequently mutated component. However, some components of SWI/SNF complexes, including , exhibit a very low mutation rate in squamous cell carcinoma (SCC), and their role in SCC remains unknown. Here, we demonstrate that the low expression of ARID1A in SCC is the result of promoter hypermethylation.
View Article and Find Full Text PDFCancer cells associated with radioresistance are likely to give rise to local recurrence and distant metastatic relapse. However, it remains unclear whether specific miRNAs have direct roles in radioresistance and/or prognosis. In this study, we find that miR-339-5p promotes radiosensitivity, and is downregulated in radioresistant subpopulations of esophageal cancer cells.
View Article and Find Full Text PDFPreoperative chemoradiotherapy (pre-CRT) has been represented as the standard treatment for locally advanced rectal cancer (LARC), but large variations of tumor radiation response to CRT have been reported in the clinic. To explore the function of microRNAs as potential therapeutic predictors of pre-CRT pathological response in LARC, we analyzed global miRNA expression in CRT-sensitive and CRT-resistant groups before treatment. MiR-345 was significantly elevated in the CRT-resistant group.
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