Hepatic carcinoma (HCC) is a lethal disease associated with high morbidity and poor prognosis. Recently years, gene therapies have offered novel modalities to improve the prognosis of HCC patients. ...MicroRNA-99a (miR-99a) is frequently down-regulated in HCC, where it acts as a tumor suppressor. Therefore, we constructed monomethoxy (polyethylene glycol)-poly(D,L-lactide-co-glycolide)-poly(L-lysine)-lactobionic acid- anti-vascular endothelial growth factor antibody (mPEG-PLGA-PLL-LA/VEGFab or PEAL-LA/VEGFab) nanoparticles (NPs) with highly specific targeting properties as carriers to restore the expression of miR-99a both in vitro and in vivo, to inhibit HCC progression. In vitro, PEAL-LA/VEGFab NPs showed more efficient delivery of miR-99a to HepG2 cells than the conventional transfection reagent Lipofectamine
2000 (Lip2000). The higher delivery efficiency associated with PEAL-LA/VEGFab NPs consequently resulted in down-regulation of target genes and suppression of the proliferation, migration and invasion of HepG2 cells. In vivo, miR-99a-PEAL-LA/VEGFab NPs inhibited tumor xenograft growth in HCC-bearing mice without causing obvious systemic toxicity. Our results demonstrate that PEAL-LA/VEGFab NPs selectively and effectively deliver miR-99a to HCC cells based on the double-targeting character of these nanoparticles, thereby offering potential for translation into effective clinical therapies for HCC.
Abstract
Background
Previous studies reported that tuberculosis (TB) is associated with an increased risk of lung cancer or the survival and mortality of lung cancer. However, the impact of ...coexisting TB on the survival of lung cancer patients was controversial. We aimed to identify risk factors on the survival rate of patients with co-existent active TB and lung cancer.
Methods
One hundred seventy-three patients diagnosed with active TB and lung cancer from January 2016 to August 2021 in Shanghai pulmonary hospital were selected and divided into two groups (≤ 6 months, > 6 months) according to the diagnosis interval between active TB and lung cancer (the order of diagnosis is not considered). The clinical characteristics and survival were analyzed. Univariate and multivariate logistic regression analyses were used to identify the risk factors for overall survival (OS).
Results
One hundred seventy-three patients were diagnosed with lung cancer and active TB. The study population exhibited a median age of 64 years, with a majority of 81.5% being male, 58.0% of patients had a history of smoking. Among those involved, 93.6% had pulmonary TB, 91.9% were diagnosed with non-small cell lung cancer (NSCLC), 76.9% were Eastern Cooperative Oncology Group (ECOG) 0–2 and 12.7% were ECOG 3–4. We observed better survival in the > 6 months group compared with the ≤ 6 months group (hazard ratio HR 0.456, 95% confidence interval CI:0.234–0.889,
P
= 0.017). The 1-, 3-, and 5- year OS rates were 94.2%, 80.3%, and 77.6%, respectively, in the > 6 months group and 88.3%, 63.8%, and 58.5%, respectively, in the ≤ 6 months group. Surgery (HR 0.193, 95% CI, 0.038–0.097;
P
= 0.046) and ECOG Performance Status (HR 12.866, 95% CI, 2.730–60.638;
P
= 0.001) were independent prognostic factors in the > 6 months group.
Conclusions
Patients diagnosed with lung cancer and active TB for more than half a year have a significantly better prognosis than those diagnosed within half a year. ECOG Performance Status and surgery might possibly affect the outcomes of patients with co-existent active TB and lung cancer.
The application of Fe3O4 nanoparticles (NPs) has made great progress in the diagnosis of disease and in the drug delivery system for cancer therapy, but the relative mechanisms of potential toxicity ...induced by Fe3O4 have not kept pace with its development in the application, which has hampered its further clinical application. In this article, we used two kinds of human hepatoma cell lines, SK-Hep-1 and Hep3B, to investigate the cytotoxic effects and the involved mechanisms of small Fe3O4 NPs with different diameters (6 nm, 9 nm, and 14 nm). Results showed that the size of NPs effectively influences the cytotoxicity of hepatoma cells: 6 nm Fe3O4 NPs exhibited negligible cytotoxicity and 9 nm Fe3O4 NPs affected cytotoxicity via cellular mitochondrial dysfunction and by inducing necrosis mediated through the mitochondria-dependent intracellular reactive oxygen species generation. Meanwhile, 14 nm Fe3O4 NPs induced cytotoxicity by impairing the integrity of plasma membrane and promoting massive lactate dehydrogenase leakage. These results explain the detailed mechanism of different diameters of small Fe3O4 NPs-induced cytotoxicity. We anticipate that this study will provide different insights into the cytotoxicity mechanism of Fe3O4 NPs, so as to make them safer to use in clinical application.
Reliable monitoring of metabolites in biofluids is critical for diagnosis, treatment, and long‐term management of various diseases. Although widely used, existing enzymatic metabolite assays face ...challenges in clinical practice primarily due to the susceptibility of enzyme activity to external conditions and the low sensitivity of sensing strategies. Inspired by the micro/nanoscale confined catalytic environment in living cells, the coencapsulation of oxidoreductase and metal nanoparticles within the nanopores of macroporous silica foams to fabricate all‐in‐one bio‐nanoreactors is reported herein for use in surface‐enhanced Raman scattering (SERS)‐based metabolic assays. The enhancement of catalytical activity and stability of enzyme against high temperatures, long‐time storage or proteolytic agents are demonstrated. The nanoreactors recognize and catalyze oxidation of the metabolite, and provide ratiometric SERS response in the presence of the enzymatic by‐product H2O2, enabling sensitive metabolite quantification in a “sample in and answer out” manner. The nanoreactor makes any oxidoreductase‐responsible metabolite a candidate for quantitative SERS sensing, as shown for glucose and lactate. Glucose levels of patients with bacterial infection are accurately analyzed with only 20 µL of cerebrospinal fluids, indicating the potential application of the nanoreactor in vitro clinical testing.
Inspired by the spatially confined micro‐/nano‐environment in living cells, a plasmonic bio‐nanoreactor is developed by the coencapsulation of enzyme and surface‐enhanced Raman scattering tags within macroporous silica foams. The nanoreactor shows enhanced biocatalytic activity and stability, and thus the capability of molecular recognition and detection provides an all‐in‐one optical biosensor for reliable in vitro metabolic testing.
The utilization of immune checkpoint inhibitors (ICIs) has become the established protocol for treating advanced non-small cell lung cancer (NSCLC). This work aimed to identify the immune-related ...gene signature that can predict the prognosis of NSCLC patients receiving ICI treatment.
The ImmPort database was queried to obtain a list of immune-related genes (IRGs). Differentially expressed IRGs in NSCLC patients were identified using the TCGA database. RNA-seq data and clinical information from NSCLC patients receiving immunotherapy were obtained from the GEO database (GSE93157 and ///). A gene signature was generated through multivariate Cox and LASSO regression analyses. The prognostic value and function of this gene signature were thoroughly investigated using comprehensive bioinformatics analyses.
A total of 6 prognostic-related genes were identified from 617 differentially expressed genes, and two prognostic-related differentially expressed genes (CAMP and IL17A) were determined to construct gene signature. Our gene signature demonstrated superior performance compared to other clinicopathological parameters in predicting the prognosis of NSCLC patients receiving immunotherapy, with an area under the ROC curve (AUC) of 0.812. Furthermore, immune infiltration analysis indicated that the high-risk group was enriched with resting CD4 T cell memory, while the low-risk group showed a "hot" tumor microenvironment that promotes anti-tumor immunity in NSCLC patients.
Gene signatures based on immune-related genes exhibited excellent indicator performance of prognosis and immune infiltration, which has the potential to be an effective biomarker for NSCLC with ICI treatment.
The combined treatment with nanoparticles and autophagy inhibitors, such as chloroquine (CQ) and hydroxychloroquine (HCQ), is extensively explored for cancer therapy. However, the toxicity of ...autophagy inhibitors and their unselective for tumoricidal autophagy have seriously hindered the application of the combined treatment. In this study, a carboxy‐functional iron oxide nanoparticle (Fe2O3@DMSA) is designed and identified to significantly exert an antitumor effect without adding CQ or HCQ. Further investigation indicates that the effective inhibition effect of Fe2O3@DMSA alone on hepatoma growth is triggered by inhibiting the fusion of autophagosomes and lysosomes to enhance tumoricidal autophagy, which is induced by intracellular iron‐retention‐induced sustained reactive oxygen species (ROS) production. Furthermore, in two hepatoma‐bearing mouse models, Fe2O3@DMSA alone effectively suppresses the growth of tumors without obvious toxic side effects. These studies offer a promising strategy for cancer therapy.
Carboxy‐functional iron oxide nanoparticles (Fe2O3@DMSA) trigger intracellular iron‐retention‐induced sustained reactive oxygen species (ROS) production to activate autophagy but block the fusion of autophagosomes and lysosomes, which efficiently inhibits hepatoma growth through enhancing tumoricidal autophagy in vitro and in vivo. Fe2O3@DMSA shows potential clinical application for hepatoma therapy.
Diallyl disulfide (DADS) is a natural organosulfur compound isolated from garlic. DADS has various biological properties, including anticancer, antiangiogenic, and antioxidant effects. However, the ...anticancer mechanisms of DADS in human esophageal carcinoma have not been elucidated, especially in vivo. In this study, MTT assay showed that DADS significantly reduced cell viability in human esophageal carcinoma ECA109 cells, but was relatively less toxic in normal liver cells. The pro-apoptotic effect of DADS on ECA109 cells was detected by Annexin V-FITC/propidium iodide (PI) staining. Flow cytometry analysis showed that DADS promoted apoptosis in a dose-dependent manner and the apoptosis rate could be decreased by caspase-3 inhibitor Ac-DEVD-CHO. Xenograft study in nude mice showed that DADS treatment inhibited the growth of ECA109 tumor in both 20 and 40 mg/kg DADS groups without obvious side effects. DADS inhibited ECA109 tumor proliferation by down-regulating proliferation cell nuclear antigen (PCNA). DADS induced apoptosis by activating a mitochondria-dependent pathway with the executor of caspase-3, increasing p53 level and Bax/Bcl-2 ratio, and downregulating the RAF/MEK/ERK pathway in ECA109 xenograft tumosr. Based on studies in cell culture and animal models, the findings here indicate that DADS is an effective and safe anti-cancer agent for esophageal carcinoma.
Attention-based approach would be a good way of detecting depression, assisting medical diagnosis and treating the patients at risk earlier. In this paper, a new approach of recognizing depression is ...proposed, which avoids eye movement event identification and directly performs clustering based on eye tracking data to obtain Regions of Interesting (ROIs), and then conducts depression recognition modelling. Based on these, a novel spatio-temporal clustering algorithm was proposed, i.e. ROI Clustering with Deflection Elimination, which takes the noisy data into consideration to betterly describe attention patterns. On the dataset with 45 depression patients and 44 healthy controls, the proposed algorithm achieved the best classification accuracy of 76.25%, which has the potential to provide methodological reference on the assessment of mental disorders based on eye movements.
Lung cancer (LC) remains the most commonly diagnosed cancer. Timely diagnosis is crucial for improving the clinical outcomes of LC patients. Serum molecular patterns reflect the physiological and ...pathological status of individuals, and are promising as diagnostic targets for malignancies. Here, we report a spectroscopic method for the rapid identification of LC based on the label-free fingerprinting of clinical serum samples with slippery liquid-infused porous surface-enhanced Raman spectroscopy (SLIPSERS). We first demonstrate the capability of SLIPSERS for the delivery and preconcentration of serum molecules into the SERS hot spots from an evaporating liquid droplet, enabling the acquisition of vibrational fingerprints of serum molecules with only 1 μL of blood serum in minutes. The averaged SLIPSERS signals of the serum sample from a cohort of 33 LC patients and 23 healthy controls reveal both metabolic and biomacromolcular alterations under LC conditions. By analyzing the SLIPSERS data with chemometric methods, we further demonstrate that the SLIPSERS profiling of serum molecular patterns allows the reliable discrimination of LCs from healthy controls. Considering the ease of operation and high efficiency, our SLIPSERS-based serum biopsy method should hold great potential for non-invasive LC diagnosis.
Direct and label-free analysis of clinical serum samples using slippery liquid-infused porous-enhanced Raman spectroscopy (SLIPSERS) enables the rapid non-invasive identification of lung cancer.
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