Keratin 17 and Collagen type 1 genes: Esophageal cancer molecular marker discovery and evaluation.

One hundred eighty pairs of tissues of esophageal squamous cell carcinoma (ESCC) were tested by the transcriptome sequencing in order to explore etiology factors. The chi-square test and correlation analysis demonstrated that the relative expression levels of keratin 17 (KRT17) and collagen type I α1 chain (COL1A1) were significantly higher in EC with diabetes. Expression of KRT17 was correlated with blood glucose (r = 0.204, p = 0.001) and tumor size (r = -0.177, p = 0.038) in patients. COL1A1 correlated with age (r = -0.170, p = 0.029) and blood glucose levels (r = 0.190, p = 0.015). Experimental results of qRT-PCR: KRT17 and COL1A1 genes were highly expressed in ESCC (p < 0.05). When the two genes were used as a combination test, the positive detection rate of EC was 90.6%, and the ROC curve had greater power. The KRT17 and COL1A1 genes had the potential to be biomarkers for the diagnosis of ESCC.

A Bioinspired Photosensitizer Performs Tumor Thermoresistance Reversion to Optimize the Atraumatic Mild-Hyperthermia Photothermal Therapy for Breast Cancer.

Mild-hyperthermia photothermal therapy (mPTT) has therapeutic potential with minimized damage to normal tissues. However, the poorly vascularized tumor area severely hampers the penetration of photothermal agents (PTAs), resulting in their heterogeneous distribution and the subsequent heterogeneous local temperature during mPTT. The presence of regions below the therapeutic 42 °C threshold can lead to incomplete tumor ablation and potential recurrence. Additionally, tumor anti-apoptosis and cytoprotection pathways, particularly activated thermoresistance, can nullify mild hyperthermia-induced tumor damage. Therefore, a bioinspired photosensitizer decorated with leucine to form biomimetic nanoclusters (CP-PLeu nanoparticles (NPs)) aimed at achieving rapid and homogeneous accumulation in tumors, is introduced. Moreover, CP-PLeu exhibits photodynamic effects that reverse tumor thermoresistance and physiological repair mechanisms, thereby inhibiting tumor resistance to hyperthermia. With the addition of NIR-II laser irradiation, CP-PLeu optimizes the therapeutic efficacy of mPTT and contributes to a minimally invasive therapeutic process for breast cancer. This therapeutic strategy, utilizing a biomimetic photosensitizer for homogeneous distribution of therapeutic temperature and photoactivated reversal of tumor thermoresistance, successfully achieves efficient breast tumor inhibition through an atraumatic mPTT process.

A Gas/phototheranostic Nanocomposite Integrates NIR-II-Peak Absorbing Aza-BODIPY with Thermal-Sensitive Nitric Oxide Donor for Atraumatic Osteosarcoma Therapy.

Photothermal therapy (PTT) has received increasing interest in cancer therapeutics owing to its excellent efficacy and controllability. However, there are two major limitations in PTT applications, which are the tissue penetration depth of lasers within the absorption range of photothermal agents and the unavoidable tissue empyrosis induced by high-energy lasers. Herein, a gas/phototheranostic nanocomposite (NA1020-NO@PLX) is engineered that integrates the second near-infrared-peak (NIR-II-peak) absorbing aza-boron-dipyrromethenes (aza-BODIPY,NA1020) with the thermal-sensitive nitric oxide (NO) donor (S-nitroso-N-acetylpenicillamine, SNAP). An enhanced intramolecular charge transfer mechanism is proposed to achieve the NIR-II-peak absorbance (λmax = 1020 nm) on NA1020, thereby obtaining its deep tissue penetration depth. The NA1020 exhibits a remarkable photothermal conversion, making it feasible for the deep-tissue orthotopic osteosarcoma therapy and providing favorable NIR-II emission to precisely pinpoint the tumor for a visible PTT process. The simultaneously investigated atraumatic therapeutic process with an enhanced cell apoptosis mechanism indicates the feasibility of the synergistic NO/low-temperature PTT for osteosarcoma. Herein, this gas/phototheranostic strategy optimizes the existing PTT to present a repeatable and atraumatic photothermal therapeutic process for deep-tissue tumors, validating its potential clinical applications.

Identification of Co-Expression Modules and Genes Associated With Tumor Progression in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a common head-and-neck cancer with a deficiency of early diagnosis and poor prognosis. To identify potential diagnostic and prognostic markers of OSCC, we firstly used weighted gene co-expression network analysis (WGCNA) to build a co-expression module from GSE42743. Next, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on specified units from selected modules utilizing Database for Annotation, Visualization, and Integrated Discovery (DAVID). Additionally, we identified and validate hub genes of these specified modules from multiple datasets like GEPIA and TCGA. In total 16 co-expression modules were built by 17,238 genes of 74 tumor samples utilizing WGCNA. Through pathway and functional enrichment analysis, the turquoise module was most firmly relevant to the cell cycle, oocyte meiosis, and p53 signaling pathway. Hub genes VRK1, NUP37, HMMR, SPC25, and RUVBL1 were identified to be related to oral cancer at both molecular level and clinical levels. The expressions of these genes differed in tumor tissues and normal tissues. Meanwhile, patients with high hub gene expression had a poor prognosis clinically. To conclude, five hub genes were identified to be relevant to oral cancer from the molecular level and the clinical level. Therefore, the detection of these genes was of great significance. They can be regarded as diagnostic and prognostic biomarkers for oral cancer. Also, they could shed light on the improvement of patients' overall survival and prognosis, which needs further analysis in the future.

Identification of the alpha linolenic acid metabolism-related signature associated with prognosis and the immune microenvironment in nasopharyngeal carcinoma.

Background: Tumor metabolism is important for cancer progression. Nevertheless, the role of the metabolism pathway and related molecules in nasopharyngeal carcinoma (NPC) is limited. Methods: Open-accessed data was downloaded from The Cancer Genome Atlas database. All the analysis was performed using the R software and the package in R environments. Results: In our study, we firstly explored the role of 21 metabolism-related pathways in NPC patients. We found that the steroid biosynthesis and biosynthesis of unsaturated fatty acids were risk factors, while the alpha linolenic acid metabolism was a protective factor. Then, the alpha linolenic acid metabolism aroused our interest. A total of 128 differentially expressed genes (DEGs) were identified, including 71 downregulated and 57 upregulated genes identified between high and low alpha linolenic acid metabolism level. Based on these DEGs, we constructed a prognosis model including DEFB4B, FOXL2NB, MDGA2, RTL1, SLURP2, TMEM151B and TSPAN19, which showed great prediction efficiency in both training and validation cohorts. Clinical correlation analysis showed that high-risk patients might have worse clinical pathology parameters. Pathway enrichment analysis showed that riskscore was positively correlated with angiogenesis, DNA repair, G2/M checkpoints, IL6/JAK/STAT3 signaling, KRAS signaling up, WNT beta-catenin signaling, PI3K/AKT/mTOR signaling, yet positively correlated with inflammatory response, xenobiotic metabolism, TNF-α signaling via NFKB and interferon-gamma response. Immune infiltration analysis showed that the riskscore was positively correlated with the M2 and M0 macrophages, but negatively correlated with neutrophils, plasma cells, follicular helper T cells and resting dendritic cells Moreover, we found that the low-risk patients might be more sensitive to immunotherapy and lapatinib. Conclusions: In all, our study identified the genes associated with alpha linolenic acid metabolism and constructed an effective prognosis model which could robustly predict NPC patients prognosis.

Study on the Synthesis and Biological Activities of N-Alkylated Deoxynojirimycin Derivatives with a Terminal Tertiary Amine.

A series of N-alkylated deoxynojirimycin (DNJ) derivatives connected to a terminal tertiary amine at the alkyl chains of various lengths were prepared. These novel synthetic compounds were assessed for preliminary glucosidase inhibition and anticancer activities in vitro. Potent and selective inhibition was observed among them. Compound 7d (IC50 = 0.052 mM) showed improved and selective inhibitory activity against ?-glucosidase compared to DNJ (IC50 = 0.65 mM). In addition, analysis of the kinetics of enzyme inhibition by using Lineweaver-Burk plots indicated that 7d inhibited ?-glu-cosidase in a competitive manner, suggesting that 7d was expected to bind to the active site of ?-glucosidase. Compounds 8b and 8c were found to be moderate and selective inhibitors of ?-glucosidase. Nevertheless, none of compounds inhib-ited the growth of B16F10 melanoma cells.

A Novel Dicyanoisophorone-Based Ratiometric Fluorescent Probe for Selective Detection of Cysteine and Its Bioimaging Application in Living Cells.

A selective and ratiometric turn-on fluorescent probe was designed and synthesized by using a novel dicyanoisophorone-based derivative and acrylate moiety. The probe displayed high stability and good selectivity to cysteine (Cys) over homocysteine (Hcy) and glutathione (GSH). It also exhibited rapid response to Cys within 180 s. Most importantly, the fluorescence intensity ratio at 590 and 525 nm (I590/I525) was linearly dependent on the Cys concentration in the range from 0 to 40 µM and the detection limit calculated to be 0.48 µM. This probe was also applied for bioimaging of intracellular Cys in living HeLa cells with low cytotoxicity.

A novel glutathione-triggered theranostic prodrug for anticancer and imaging in living cells.

A novel theranostic prodrug was designed and synthesized by conjugating a naphthalimide derivative with vitamin D2 via a disulfide linker. The prodrug featured a highly selective detection process for glutathione (GSH) and showed a red-shifted fluorescence within 30 min. Notably, it also exhibited antitumor activity similar to vitamin D2 and could be monitored by cellular imaging.