Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new ...tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Proteogenomic characterization and integrative and comparative genomic analysis provide a functional context to annotate genomic abnormalities with prognostic value.
Here, we analyzed the proteomes ...and performed whole exome and transcriptome sequencing and single nucleotide polymorphism array profiling for 2 sets of triplet samples comprised of normal colorectal tissue, primary CRC tissue, and synchronous matched liver metastatic tissue.
We identified 112 CNV-mRNA-protein correlated molecules, including up-regulated COL1A2 and BGN associated with prognosis, and four strongest hot spots (chromosomes X, 7, 16 and 1) driving global mRNA abundance variation in CRC liver metastasis. Two sites (DMRTB1
and PARP4
) were revealed to frequent mutate only in the liver metastatic cohort and displayed dysregulated protein abundance. Moreover, we confirmed that the mutated peptide number has potential prognosis value and somatic variants displayed increased protein abundance, including high MYH9 and CCT6A expression, with clinical significance.
Our proteogenomic characterization and integrative and comparative genomic analysis provides a new paradigm for understanding human colon and rectal cancer liver metastasis.
ClinicalTrials, NCT02917707. Registered 28 September 2016, https://clinicaltrials.gov/ct2/show/NCT02917707 .
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An electrochemical epoxidation of unactivated olefins using water as the source of oxygen atoms has been developed. The epoxidation reaction employs seminormal-BrCH2CH2OH as the mediator, which shows ...good functional group compatibility, and can easily be performed on the gram scale. A wide range of unactivated olefins could be tolerated to give the functionalized epoxides with satisfactory results at room temperature.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There is increasing evidence that liver cancer stem cells (LCSCs) contribute to hepatocellular carcinoma (HCC) initiation and progression. MicroRNA (miRNA) plays a significant functional role by ...directly regulating respective targets in LCSCs-triggered HCC, however, little is known about the function of the miRNA-302 family in LCSCs.
MiRNAs microarray was used to detect the miRNAs involved in LCSCs maintenance and differentiation. Biological roles and the molecular mechanism of miRNA-302a/d and its target gene E2F7 were detected in HCC in vitro. The expression and correlation of miRNA-302a/d and E2F7 in HCC patients was evaluated by quantitative PCR and Kaplan-Meier survival analysis.
We found that the miRNA-302 family was downregulated during the spheroid formation of HCC cells and patients with lower miRNA-302a/d expression had shorter overall survival (OS) and progression-free survival (PFS). Moreover, E2F7 was confirmed to be directly targeted and inhibited by miRNA-302a/d. Furthermore, concomitant low expression of miRNA-302a/d and high expression of E2F7 correlated with a shorter median OS and PFS in HCC patients. Cellular functional analysis demonstrated that miRNA-302a/d negatively regulates self-renewal capability and cell cycle entry of liver cancer stem cells via suppression of its target gene E2F7 and its downstream AKT/β-catenin/CCND1 signaling pathway.
Our data provide the first evidence that E2F7 is a direct target of miRNA-302a/d and miRNA-302a/d inhibits the stemness of LCSCs and proliferation of HCC cells by targeting the E2F7/AKT/β-catenin/CCND1 signaling pathway.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A site-selective electrochemical C–H bromination of (hetero)arenes with 2-bromoethan-1-ol through paired electrolysis has been developed. The C–H bromination reactions depend on the anodic oxidation ...of Br− produced by the cathodic reduction of 2-bromoethan-1-ol with available ethylene oxide and hydrogen evolution. The method has good compatibility with common functional groups and the scale-up electrolysis can easily be performed. A wide variety of brominated products were obtained with satisfactory yields at room temperature in a simple undivided cell.
An electrochemical monofluoroalkylation cyclization of
-arylacrylamides to synthesize monofluorinated 2-oxindoles has been developed, which employs common dimethyl 2-fluoromalonate as a ...monofluoroalkyl radical precursor and obviates the use of prefunctionalized monofluoroalkylation reagents and sacrificial oxidants. A variety of monofluorinated nitrogen-containing heterocyclic compounds were efficiently obtained with satisfactory yields from readily available materials.
2D MXene, Ti3C2 (TC), has displayed enormous potential in applications in photothermal therapy (PTT), attributing to its biocompatibility and outstanding photothermal conversion capability. However, ...some tumor ablations are difficult to be realized completely by monotherapy due to the essential defects of monotherapy and intricate tumor microenvironment (TME). In this work, the appropriate doped Fe2+ ions are anchored into the layers of 2D ultrathin TC nanosheets (TC NSs) to synthesize a novel multifunctional nanoshell of Fe(II)‐Ti3C2 (FTC) through interlayer electrostatic adsorption. FTC possesses superior photothermal conversion efficiency (PTCE) than TC NSs, attributing to the enhanced conductivity promoted by interlaminar ferrous ion‐channels. Moreover, Fenton reaction based on ferrous ions endows FTC the abilities of reactive oxide species (ROS) releasing and glutathione (GSH) suppression triggered by near‐infrared (NIR) laser, featuring splendid biocompatibility and curative effect in hypoxic TME. Meanwhile, magnetic resonance imaging (MRI) responding in FTC reveals the potential as an integrated diagnosis and treatment nanoplatform. FTC could provide new insights into the development of multimoded synergistic nanoplatform for biological applications, especially breaking the shackles of MXenes merely used as a photo‐thermal agent (PTA), adopting it to bioimaging sensor and drug loading.
Near‐infrared (NIR) activated multimodal nanoplatform Fe‐Ti3C2 (FTC) is developed by electrostatic adsorption between Ti3C2 and Fe(II). FTC can generate reactive oxygen species (ROS) and suppress glutathione (GSH) under NIR excitation. FTC has the superior photothermal performance than Ti3C2. The ferrous ions also endow FTC the ability to serve as a T1 and T2 dual‐responding magnetic resonance contrast agent.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract Organometallic catalysts such as titanium‐based ones are often used for the melt polycondensation to obtain polyesters. However, they are prone to hydrolysis and may discolor, which may have ...adverse effects on the molecular weight of the resulting polyesters and their applications. This work aims to use functionalized UiO‐66 catalysts for the melt polycondensation of polyesters composed of 1,3‐propanediol and 1,10‐decanedioic acid ether. The melt polycondensation proceeds in two steps: esterification and polycondensation. A catalytic mechanism is proposed. Compared with tetrabutyl titanate, a classical catalyst, the functionalized UiO‐66 ones are more water resistant, less toxic to, and do not discolor. It yields poly(1,3‐propylene sebacate) with higher molecular weights. Thus, they are efficient and greener catalysts.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Traditional chemotherapy faces challenges related to limited drug efficacy and adverse reactions. Intelligent nanocarrier drug delivery systems (INDDSs) promise improved treatment outcomes with ...reduced toxicity. However, several clinical challenges persist in achieving rapid drug release and real-time monitoring. Herein, a ROS-responsive amphiphilic copolymer was synthesized: polyethylene glycol (mPEG-TK-OH) with ROS-responsive thioketal (TK) as the macromolecular initiator, and enzymatic ring-opening polymerization of caprolactone was performed. Small molecules of tetraphenylethylene (TPE) with aggregation-induced emission (AIE) properties were added to the polymer's terminus to enable fluorescence imaging and the ROS-responsive amphiphilic copolymer mPEG-TK-PCL-TPE with AIE properties is formed and enhances drug release monitoring through fluorescence resonance energy transfer (FRET) between TPE and the hydrophobic anti-cancer drug DOX. Leveraging distinct ROS levels between tumor and normal cells, these ROS-responsive nanomicelles effectively respond to high intracellular redox-active species and release DOX. The mPEG-TK-PCL-TPE micelles displayed a suitable size, high drug loading, and excellent imaging quality.
In vitro
cell experiments confirmed their biocompatibility and efficacy in inhibiting 4T1 tumor cells. This ROS-responsive amphiphilic copolymer, incorporating the AIE structure, introduces new opportunities for cancer treatment, enabling real-time drug release tracking and improving therapeutic outcomes.
The ROS-responsive amphiphilic copolymer micelles mPEG-TK-PCL-TPE, combined with AIE properties, enable real-time drug release monitoring and intracellular tracing, and ensures stable circulation and rapid release in tumors.
Increasing evidence has shown that microRNAs (miRNAs) play a significant functional role by directly regulating respective targets in cancer stem cell (CSC)-induced non-small cell lung cancer (NSCLC) ...progression and resistance to therapy. In this study, we found that hsa-miR-124a was downregulated during spheroid formation of the NSCLC cell lines SPC-A1 and NCI-H1650 and NSCLC tissues compared with normal lung cells and tissues. Patients with lower hsa-miR-124a expression had shorter overall survival (OS) and progression free survival (PFS). Moreover, ubiquitin-specific protease 14 (USP14) was confirmed to be a direct target of hsa-miR-124a. Furthermore, concomitant low hsa-miR-124a expression and high USP14 expression were correlated with a shorter median OS and PFS in NSCLC patients. Cellular functional analysis verified that the tumor suppressor hsa-miR-124a negatively regulated cell growth and self-renewal, and promoted apoptosis and gefitinib sensitivity of lung cancer stem cells by suppressing its target gene USP14. Our results provide the first evidence that USP14 is a direct target of hsa-miR-124a, and that hsa-miR-124a inhibits stemness and enhances the gefitinib sensitivity of NSCLC cells by targeting USP14. Thus, hsa-miR-124a and USP14 may be useful as tumor biomarkers for the diagnosis and treatment of NSCLC.
•Hsa-miR-124a regulates growth, self-renewal and gefitinib sensitivity of LCSCs by suppressing USP14.•USP14 is a direct target of hsa-miR-124a.•NSCLC patients with high USP14 expression and low hsa-miR-124a expression had significantly decreased OS and PFS.•Hsa-miR-124a and USP14 may be useful as tumor biomarkers for the diagnosis and treatment of NSCLC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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