Assessing the utility of MRI-based vertebral bone quality (VBQ) for predicting lumbar pedicle screw loosening.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: The purpose of this study is to assess the potential of utilizing the MRI-based vertebral bone quality (VBQ) score as a predictive tool for pedicle screw loosening (PSL) in patients who have undergone pedicle screw fixation and to identify risk factors associated with VBQ scores. METHODS: One hundred and sixteen patients who had undergone pedicle screw fixation between December 2019 and January 2021 and had more than a year of follow-up were divided into two groups of PSL and non-PSL. The radiological and clinical parameters investigated were age, gender, body mass index, the VBQ score, length of fusion and the DXA T-score. RESULTS: Of the 116 patients included in the study, 22 patients developed pedicle screw loosening after surgery (18.97%). VBQ score of PSL group was higher than the non-PSL group (3.61 ± 0.63 vs. 2. 86 ± 0.43, p < 0.001). According to logistic regression, PSL was independently linked with a higher VBQ score (OR = 3.555, 95% confidence interval [1.620-7.802], p < 0.005). The AUC of predicting screw loosening was 0.774 (p < 0.001) for VBQ score, and the best threshold was 3.055 (sensitivity, 81.8%; specificity, 71.3%). High VBQ score was associated with age (r (114) = 0.29, p = 0.002), while it was not negatively correlated with T-scores of each part. CONCLUSION: VBQ score is an independent predictor of pedicle screw loosening, with higher scores indicating a greater risk. Our results showed that older patients and women had higher VBQ scores.

Hypoxia induced cell dormancy of salivary adenoid cystic carcinoma through miR-922/DEC2 axis.

BACKGROUND: Hypoxia has been shown to induce cancer cells to become dormant meanwhile these cells inclined to disseminate and eventually cause metastasis. However, the molecular mechanism is still elusive. The purpose is to explore whether dormancy-associated microRNAs (DmiRs) get involved in hypoxia-induced cell dormancy of salivary adenoid cystic carcinoma (SACC). MATERIAL AND METHODS: This study performed multi-perspective investigation of the biological effects of miR-922/DEC2 on SACC based on clinical samples, 2D and 3D in vitro model and nude mice in vivo model, based on our previous study of overexpression of DEC2 inducing SACC cellular dormancy. RESULTS: According to the existing microRNA array of SACC tissue, we found that miR-922 was upregulated in SACC tissue and was inversely correlated with DEC2, suggesting that miR-922 might participate in the activation of SACC cell dormancy as a DmiR. Then, we found miR-922 low SACC cells exhibited cell dormancy and a low level of fatty acid oxidation with propensity for lipid droplets accumulation through DEC2. Moreover, HIF1a downregulated the level of miR-922 to induce SACC cell dormancy. In addition, in xenografts of nude mice the inhibition of miR-922 attenuated the growth of primary tumor and the lung metastasis of SACC. CONCLUSIONS: miR-922/DEC2 axis was necessary to hypoxia-induced cell dormancy and played an important role in the lipid metabolism reprogramming of SACC.

M1 macrophages induce PD-L1hi cell-led collective invasion in HPV-positive head and neck squamous cell carcinoma via TNF-α/CDK4/UPS14.

BACKGROUND: Although the roles of PD-L1 in promoting tumor escape from immunosurveillance have been extensively addressed, its non-immune effects on tumor cells remain unclear. METHODS: The spatial heterogeneity of PD-L1 staining in human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) tissues was identified by immunohistochemistry. Three-dimensional (3D) specific cell-led invasion assay and 3D cancer spheroid model were used to investigate the roles of PD-L1hileader cells in collective invasion. The impact of M1 macrophages on specific PD-L1 expression in leader cells and its mechanisms were further studied. Finally, the effect of combination therapy of anti-PD-L1 and CDK4 inhibitor on HPV-positive tumors were evaluated on a mice model. RESULTS: Here, we observed a distinctive marginal pattern of PD-L1 expression in HPV-positive HNSCC tissues. By mimicking this spatial pattern of PD-L1 expression in the 3D invasion assay, we found that PD-L1hi cells led the tumor collective invasion. M1 macrophages induced specific PD-L1 expression in leader cells, and depletion of macrophages in tumor-bearing mice abrogated PD-L1hileader cells and collective invasion. Mechanistically, TNF-α secreted by M1 macrophages markedly increased the abundance of PD-L1 via CDK4/ubiquitin-specific peptidase 14-mediated deubiquitination of PD-L1. We also found that suppression of CDK4 enhanced the efficacy of anti-PD-L1 therapy in an E6/E7 murine model. CONCLUSIONS: Our study identified TNF-α/CDK4/ubiquitin-specific peptidase 14-mediated PD-L1 stability as a novel mechanism underlying M1 macrophage-induced PD-L1hileader cells and collective tumor invasion, and highlighted the potential of the combination therapy of anti-PD-L1 and CDK4 inhibitor for HPV-positive HNSCC.

TACE Combined with Lenvatinib and Camrelizumab for Unresectable Multiple Nodular and Large Hepatocellular Carcinoma (>5 cm).

BACKGROUND: The incidence and mortality of hepatocellular carcinoma (HCC) had increased globally over the past decades. Previous studies found that transarterial chemoembolization (TACE) combined with lenvatinib had also shown efficacy in the unresectable HCC. We aimed to evaluate the safety and efficacy of TACE combined with lenvatinib and camrelizumab to treat unresectable multiple nodular and large HCC (>5 cm). MATERIALS AND METHODS: Between November 2018 and June 2021, we retrospectively recruited 82 patients with unresectable multiple nodular and large HCC (BCLC stage B or C with a single nodular diameter of >5 cm). Of the patients who had not previously been treated, 33 patients received TACE + lenvatinib + camrelizumab (group A, TLC), and 49 patients treated with TACE + lenvatinib (group B, TLB) as the initial treatment. Related efficacy and safety results were recorded and assessed. RESULTS: The median follow-up periods of groups A and B were 14.5 ± 7.9 months (range, 3-36) and 12.5 ± 8.2 months (range, 3-32), respectively (P = 0.799). The progression-free survival (PFS) of groups A and B was 9.4 months and 5.9 months (P < 0.01), respectively, and overall survival (OS) was significantly longer in group A (16.4 months vs 11.0 months, P < 0.01). In group A, the local response rate (LRR) and disease control rate (DCR) were 51.5% and 81.8%, respectively, which was higher than the corresponding 46.9% and 77.6% observed in group B (P = 0.233; 0.429). Patients with BCLC B stage had better PFS and OS (P < 0.05). The BCLC stage was an independent factor that affected PFS and OS. There were no massive bleeding or treatment-related deaths. CONCLUSIONS: In patients with unresectable multiple nodular and large HCC (single nodular diameter of >5 cm), TACE combined with target therapy and immunotherapy is safe and effective.

Transarterial Chemoembolization Combined with Atezolizumab Plus Bevacizumab or Lenvatinib for Unresectable Hepatocellular Carcinoma: A Propensity Score Matched Study.

Purpose: Combined transarterial chemoembolization (TACE) and Lenvatinib (LEN) treatment (LEN-TACE) has been shown to be beneficial. We aimed to evaluate retrospectively Atezolizumab plus Bevacizumab (Atezo/Bev)-TACE compared with LEN-TACE as a first-line therapy for unresectable HCC. Patients and Methods: From October 2020 to October 2022, data from 98 consecutive HCC patients were analyzed. After propensity score matching, two cohorts of 34 patients who received either Atezo/Bev-TACE or LEN-TACE were studied. We compared overall survival (OS), progression-free survival (PFS), duration of response, objective response rate (ORR) and disease control rate (DCR) based on RECIST 1.1 and mRECIST, as well as safety outcome between the two cohorts. Results: The 6-month and 12-month OS rates were 85.3% (95% CI 73.5-97.0) and 75.4% (95% CI 53.6-85.7) in the Atezo/Bev-TACE group, and 88.2% (95% CI 76.5-97.1) and 79.2% (95% CI 63.6-90.9) in the LEN-TACE group, respectively. The hazard ratio for death in the Atezo/Bev-TACE group compared to the LEN-TACE group was 1.09 (95% CI 0.47-2.51; P = 0.837). The median PFS was 7.03 months (95% CI 3.89-10.17) in the Atezo/Bev-TACE group and 6.03 months (95% CI 0-14.14) in the LEN-TACE group (HR 1.21; 95% CI 0.66-2.21; P = 0.545). No significant difference in ORR and DCR between the two groups was observed either according to RECIST 1.1 or mRECIST standards. Incidence rates of hand-foot skin reaction (35.3% vs 5.9%, P = 0.003) and proteinuria (17.9% vs 2.9%, P = 0.046) were significantly higher in the LEN-TACE group. Conclusion: Atezo/Bev-TACE and LEN-TACE showed comparable efficacy and safety as first-line therapies for unresectable HCC patients.

Safety, efficacy, and survival of drug-eluting beads-transarterial chemoembolization vs. conventional-transarterial chemoembolization in advanced HCC patients with main portal vein tumor thrombus.

OBJECTIVES: To compare the efficacy, overall survival (OS) and safety of drug-eluting beads-TACE (DEB-TACE) and C-TACE as initial treatment in advanced hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (mPVTT). METHODS: The medical records of consecutive advanced HCC patients with mPVTT who underwent initial DEB-TACE or C-TACE from September 2015 to October 2021 were retrospectively evaluated. Treatment crossover was allowed in this retrospective research. The adverse events, disease control rate (DCR), time to tumor progression (TTP) and OS of patients who underwent DEB-TACE were compared with those of patients who underwent C-TACE. RESULTS: Eighty-three patients were included: 42 patients in DEB-TACE group and 41 patients in C-TACE group. DEB-TACE could be safely performed in HCC patients with mPVTT, and they gained a better DCR than those submitted to the C-TACE (76.2% vs. 53.7%, P = 0.031), which might have resulted in longer TTP (median TTP: 9.0 months vs. 3.0 months, P < 0.001). Furthermore, DEB-TACE showed significant OS benefits compared with C-TACE (median OS: 12.0 months vs. 5.0 months, P < 0.001). DEB-TACE, absence of arterioportal shunts (APS), leisons with capsular non-infiltration were found to be independent prognostic factors for better OS. Furthermore, subgroup analysis proved that patients with good DCR gained longer OS in DEB-TACE group. CONCLUSIONS: DEB-TACE could be safely performed and improve the DCR of HCC patients with mPVTT, which resulting in longer TTP and OS, compared with C-TACE.

Idarubicin versus epirubicin in drug-eluting beads-transarterial chemoembolization for treating hepatocellular carcinoma: A real-world retrospective study.

The purpose of this study was to compare the efficacy and safety of idarubicin-loaded drug-eluting beads-transarterial chemoembolization (IDA-TACE) and epirubicin-loaded drug-eluting beads-TACE (EPI-TACE) in treating hepatocellular carcinoma (HCC). All patients with HCC treated with TACE in our hospital between June 2020 and January 2022 were screened. The included patients were divided into the IDA-TACE group and EPI-TACE group to compare overall survival (OS), time to progression (TTP), objective response rate (ORR), and adverse events. There were 55 patients each in the IDA-TACE and EPI-TACE groups. Compared with the EPI-TACE group, the median TTP in the IDA-TACE group was not significantly different (10.50 vs. 9.23 months; HR 0.68; 95% CI 0.40-1.16; P = 0.154), whereas the survival status in the IDA-TACE group tended to be better (neither achieved; HR 0.47; 95% CI 0.22-1.02; P = 0.055). Based on the Barcelona Clinic Liver Cancer staging system for subgroup analysis, considering stage C patients, the IDA-TACE group performed significantly better in terms of ORR (77.1% vs. 54.3%, P = 0.044), median TTP (10.93 vs. 5.20 months; HR 0.46; 95% CI 0.24-0.89; P = 0.021), and median OS (not achieved vs. 17.80 months; HR 0.41; 95% CI 0.18-0.93; P = 0.033). Considering stage B patients, there were no significant differences between the IDA-TACE and EPI-TACE groups in terms of ORR (80.0% vs. 80.0%, P = 1.000), median TTP (10.20 vs. 11.2 months; HR 1.41; 95% CI 0.54-3.65; P = 0.483), or median OS (neither achieved, HR 0.47; 95% CI 0.04-5.24; P = 0.543). Notably, leukopenia was more common in the IDA-TACE group (20.0%, P = 0.052), and fever was more common in the EPI-TACE group (49.1%, P = 0.010). IDA-TACE was more effective than EPI-TACE in treating advanced-stage HCC and comparable in treating intermediate-stage HCC.

Screening differential circular RNA expression profiles and the potential role of hsa_circ_0085465 in liver cancer.

Aims: This study aimed to screen the circular RNAs (circRNAs) that are differentially expressed between liver cancer and paired paracarcinoma tissues and then elucidate their role in cancer progression. Materials and Methods: High-throughput sequencing of cancer and paired paracarcinoma tissues was followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the parental genes of the differentially expressed circRNAs, which were also verified via real-time quantitative polymerase chain reaction analysis of the tissues. In addition, the function of selected circRNAs was determined using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)-2H-tetrazolium (MTS) and transwell assays. Results: Total 218 and 121 circRNAs were differentially upregulated and downregulated, respectively; these were mainly enriched with GO and KEGG terms related to biological functions. From five representatives of the differentially expressed circRNAs, we selected hsa_circ_0085465 for further analysis, discovering that its overexpression promoted the proliferation, migration, and invasion of 97 L cells. Conclusion: Taken together, our results suggest that hsa_circ_0085465 is relevant to liver cancer progression.

DEM-TACE as the initial treatment could improve the clinical efficacy of the hepatocellular carcinoma with portal vein tumor thrombus: a retrospective controlled study.

BACKGROUND: Conventional-transarterial chemoembolization (C-TACE) was proven to improve overall survival (OS) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT), drug-eluting microsphere-TACE (DEM-TACE) was supposed to provide more benefit than C-TACE in this respect. PURPOSE: To compare the safety and efficacy between DEM-TACE and C-TACE as the initial treatment in HCC patients with PVTT and to identify prognostic factors of OS. METHODS: The medical records of advanced HCC patients with PVTT who underwent DEM-TACE or C-TACE as the initial thearpy from September 2015 with mean follow-up time 14.9 ± 1.2 (95% CI 12.6-17.2) months were retrospectively evaluated. A total of 97 patients were included, 49 patients in the DEM-TACE group and 48 in the C-TACE group. Adverse events (AEs) related to TACE were compared. Tumor and PVTT radiologic response, time to tumor progression (TTP) and OS were calculated and compared in both groups. RESULTS: Patients in DEM-TACE group had a better radiologic response (Tumr response: 89.8% vs. 75.0%; PVTT response: 85.7% vs. 70.8%; overall response: 79.6% vs. 58.3%, P = 0.024) and longer TTP (7.0 months vs. 4.0 months, P = 0.040) than patients in C-TACE group. A lower incidence of abdominal pain was found in the DEM-TACE group than in C-TACE group (21 vs. 31, P = 0.032), but there were no significant differences between DEM-TACE and C-TACE patients in any other AEs reported. When compared to C-TACE, DEM-TACE also showed significant OS benefits (12.0 months vs. 9.0 months, P = 0.027). DEM-TACE treatment, the absence of arterioportal shunt (APS), lower AFP value and better PVTT radiologic response were the independent prognostic factors for OS in univariate/multivariate analyses, which provided us with a guide for better patient selection. CONCLUSIONS: Based on our retrospective study, DEM-TACE can be performed safely and might be superior to C-TACE as the initial treatment for HCC patients with PVTT. TRIAL REGISTRATION: Retrospectively registered.

Hypermethylation of PRKCZ Regulated by E6 Inhibits Invasion and EMT via Cdc42 in HPV-Related Head and Neck Squamous Cell Carcinoma.

PURPOSE: To study the role of target genes with aberrant DNA methylation in HPV+ HNSCC. METHODS: A HumanMethylation450 BeadChip array (Illumina) was used to identify differentially methylated genes. CCK-8, flow cytometry, wound healing, and cell invasion assays were conducted to analyze the biological roles of PRKCZ. Western blot, qRT-PCR, immunohistochemistry, and animal studies were performed to explore the mechanisms underlying the functions of PRKCZ. RESULTS: We selected PRKCZ, which is associated with HPV infection, as our target gene. PRKCZ was hypermethylated in HPV+ HNSCC patients, and PRKCZ methylation status was negatively related to the pathological grading of HNSCC patients. Silencing PRKCZ inhibited the malignant capacity of HPV+ HNSCC cells. Mechanistically, HPV might promote DNMT1 expression via E6 to increase PRKCZ methylation. Cdc42 was required for the PRKCZ-mediated mechanism of action, contributing to the occurrence of epithelial-mesenchymal transition (EMT) in HPV+ HNSCC cells. In addition, blocking PRKCZ delayed tumor growth in HPV16-E6/E7 transgenic mice. Cdc42 expression was decreased, whereas E-cadherin levels increased. CONCLUSION: We suggest that PRKCZ hypermethylation induces EMT via Cdc42 to act as a potent tumor promoter in HPV+ HNSCC.

DNA N6-methyladenine involvement and regulation of hepatocellular carcinoma development.

DNA N6-methyladenine (6 mA) is a new type of DNA methylation identified in various eukaryotic cells. However, its alteration and genomic distribution features in hepatocellular carcinoma (HCC) remain elusive. In this study, we found that N6AMT1 overexpression increased HCC cell viability, suppressed apoptosis, and enhanced migration and invasion, whereas ALKBH1 overexpression induced the opposite effects. Further, 23,779 gain-of-6 mA regions and 11,240 loss-of-6 mA regions were differentially identified in HCC tissues. The differential gain and loss of 6 mA regions were considerably enriched in intergenic regions. Moreover, 7% of the differential 6 mA modifications were associated with tumors, with 60 associated with oncogenes and 57 with tumor suppressor genes (TSGs), and 17 were common to oncogenes and TSGs. The candidate genes affected by 6 mA were filtered by gene ontology (GO) and RNA-seq. Using quantitative polymerase chain reaction (qPCR), BCL2 and PARTICL were found to be correlated with DNA 6 mA in certain HCC processes.

Aspirin-induced long-term tumor remission in hepatocellular carcinoma with adenomatous polyposis coli stop-gain mutation: A case report.

BACKGROUND: Targeted therapy based on pathway analysis of hepatitis B-related hepatocellular carcinoma (HCC) may be a promising remedy. CASE SUMMARY: The present case involved an advanced hepatocellular carcinoma (HCC) patient who did not receive local regional therapy and was intolerant to sorafenib. Total RNA extracted from the patient's tumor tissue was used to obtain the gene mutation profile. The c.3676A>T and c.4402A>T stop-gain mutations in adenomatous polyposis coli (APC) were the most prevalent (42.2% and 35.1%, respectively). MutationMapper analysis indicated that the functional domain of APC was lost in the two APC mutant genes. APC is a major suppressor of the Wnt signaling pathway. Thus, the Wnt pathway was exclusively activated due to APC dysfunction, as other elements of this pathway were not found to be mutated. Aspirin has been reported to suppress the Wnt pathway by inducing ß-catenin phosphorylation through the activation of glycogen synthase kinase 3 beta via cyclooxygenase-2 pathway inhibition. Therefore, aspirin was administered to the patient, which achieved four years of disease control. CONCLUSION: Exclusive mutations of APC of all the Wnt pathway elements could be a therapeutic target in HCC, with aspirin as an effective treatment option.

Insight Into the Molecular Mechanism of Podophyllotoxin Derivatives as Anticancer Drugs.

Podophyllotoxin (PTOX) is a biologically active compound derived from the podophyllum plant, and both it and its derivatives possess excellent antitumor activity. The PTOX derivatives etoposide (VP-16) and teniposide (VM-26) have been approved by the U.S. Food and Drug Administration (FDA) for cancer treatment, but are far from perfect. Hence, numerous PTOX derivatives have been developed to address the major limitations of PTOX, such as systemic toxicity, drug resistance, and low bioavailability. Regarding their anticancer mechanism, extensive studies have revealed that PTOX derivatives can induce cell cycle G2/M arrest and DNA/RNA breaks by targeting tubulin and topoisomerase II, respectively. However, few studies are dedicated to exploring the interactions between PTOX derivatives and downstream cancer-related signaling pathways, which is reasonably important for gaining insight into the role of PTOX. This review provides a comprehensive analysis of the role of PTOX derivatives in the biological behavior of tumors and potential molecular signaling pathways, aiming to help researchers design and develop better PTOX derivatives.

The interplay between m6A modification and non-coding RNA in cancer stemness modulation: mechanisms, signaling pathways, and clinical implications.

Cancer stemness, mainly consisting of chemo-resistance, radio-resistance, tumorigenesis, metastasis, tumor self-renewal, cancer metabolism reprogramming, and tumor immuno-microenvironment remodeling, play crucial roles in the cancer progression process and has become the hotspot of cancer research field in recent years. Nowadays, the exact molecular mechanisms of cancer stemness have not been fully understood. Extensive studies have recently implicated that non-coding RNA (ncRNA) plays vital roles in modulating cancer stemness. Notably, N6-methyladenosine (m6A) modification is of crucial importance for RNAs to exert their biological functions, including RNA splicing, stability, translation, degradation, and export. Emerging evidence has revealed that m6A modification can govern the expressions and functions of ncRNAs, consequently controlling cancer stemness properties. However, the interaction mechanisms between ncRNAs and m6A modification in cancer stemness modulation are rarely investigated. In this review, we elucidate the recent findings on the relationships of m6A modification, ncRNAs, and cancer stemness. We also focus on some key signaling pathways such as Wnt/ß-catenin signaling, MAPK signaling, Hippo signaling, and JAK/STAT3 signaling to illustrate the underlying interplay mechanisms between m6A modification and ncRNAs in cancer stemness. In particular, we briefly highlight the clinical potential of ncRNAs and m6A modifiers as promising biomarkers and therapeutic targets for indicating cancer stemness properties and improving the diagnostic precision for a wide variety of cancers.

The Clinical Value of Computed Tomography (CT)-Guided 125I Brachytherapy for Locally Advanced Non-Small Cell Lung Cancer After Progression of Concurrent Radiochemotherapy.

PURPOSE: To further evaluate the efficacy and safety of computed tomography (CT)-guided iodine 125 (125I) brachytherapy to treat locally advanced non-small cell lung cancer (NSCLC) after progression of concurrent radiochemotherapy (CCRT). METHODS: This study obtained written consent from all patients and was approved by our institution. From January 2006 to June 2018, 210 NSCLC patients (progression of first-line CCRT) were retrospectively recruited and then divided into two groups. A total of 116 patients were given CT-guided 125I brachytherapy and second-line chemotherapy (group A), and 94 were treated with second-line chemotherapy alone (group B). RESULTS: In group A, local response rate (LRR) within 3 years was significantly better (P<0.05). Mean survival time [progression-free survival time (PFST) and overall survival (OS)] was 15.1±1.4 months and 21.2±1.6 months in group A compared with 10.0±1.4 months and 16.2±1.7 months in group B (PFST: P<0.01, HR=1.472, 95% CI 1.097-1.975; OS: P = 0.036, HR=1.342, 95% CI 1.005-1.791). Tumor size and No. of first cycle chemotherapy were independent factors that affected survival, ≤3cm largest tumor diameter and more than 4 first cycles of chemotherapy showed longer PFST and OS (P<0.05). Tumor-related clinical symptoms were relieved in group A (P<0.01). No serious complications occurred in the two groups. CONCLUSION: 125I brachytherapy is effective and safe in locally advanced NSCLC after progression of CCRT.

A Gas-Steamed MOF Route to P-Doped Open Carbon Cages with Enhanced Zn-Ion Energy Storage Capability and Ultrastability.

Carbon micro/nanocages have received great attention, especially in electrochemical energy-storage systems. Herein, as a proof-of-concept, a solid-state gas-steamed metal-organic-framework approach is designed to fabricate carbon cages with controlled openings on walls, and N, P dopants. Taking advantage of the fabricated carbon cages with large openings on their walls for enhanced kinetics of mass transport and N, P dopants within the carbon matrix for favoring chemical adsorption of Zn ions, when used as carbon cathodes for advanced aqueous Zn-ion hybrid supercapacitors (ZHSCs), such open carbon cages (OCCs) display a wide operation voltage of 2.0 V and an enhanced capacity of 225 mAh g-1 at 0.1 A g-1 . Also, they exhibit an ultralong cycling lifespan of up to 300 000 cycles with 96.5% capacity retention. Particularly, such OCCs as electrode materials lead to a soft-pack ZHSC device, delivering a high energy density of 97 Wh kg-1 and a superb power density of 6.5 kW kg-1 . Further, the device can operate in a wide temperature range from -25 to + 40 °C, covering the temperatures for practical applications in daily life.

CXCR5 induces perineural invasion of salivary adenoid cystic carcinoma by inhibiting microRNA-187.

CXCR5 played critical roles in tumorigenesis and metastasis. Nevertheless, little was known about the involvement of CXCR5 in perineural invasion (PNI) of salivary adenoid cystic carcinoma (SACC). Here, we confirmed upregulation of CXCR5 in SACC specimens and cells and identified that CXCR5 exhibited a significant positive correlation with PNI. Functionally, knockdown of CXCR5 suppressed SACC cells migration, invasion and PNI ability, whereas CXCR5 overexpression displayed the opposite effects. Moreover, CXCR5 downregulated microRNA (miR)-187, which could competitively sponge S100A4. The PNI-inhibitory effect of CXCR5 knockdown or miR-187 overexpression could be reversed by elevated expression of S100A4. Conjointly, our data revealed that CXCR5 facilitated PNI through downregulating miR-187 to disinhibit S100A4 expression in SACC.

Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma.

BACKGROUND: Patients were prone to have poor prognosis once dormant tumor cells being reactivated. However, the molecular mechanism of tumor cell dormancy remains poorly understood. This study aimed to investigate the function of DEC2 in the dormancy of salivary adenoid cystic carcinoma (SACC) in vitro and vivo. METHODS: The function of DEC2 in tumor dormancy of SACC was investigated in nude mice by establishing primary and lung metastasis model. Meanwhile, the interaction between hypoxia and SACC dormancy and the role of DEC2 were demonstrated through CoCl2 induced hypoxia-mimicking microenvironments. Furthermore, the expression of DEC2 was detected by immunohistochemical staining in primary SACC samples with and without recurrence. RESULTS: In the primary SACC, DEC2 overexpression inhibited cell proliferation, increased cell population arrested in G0/G1 phase, and participated in dormancy regulation, which limited tumor growth. Intriguingly, in the model of lung metastasis, the level of DEC2 was reduced significantly and resulted in dormancy exit and growth resumption of SACC cells. Then, we found that DEC2 may associate with hypoxia in contributing to tumor dormancy, which might provide a possible cue to explain the different roles of DEC2 in primary and metastasis lesions. And overexpression of DEC2 induced dormancy and promoted migration and invasion through activating EMT program. Finally, DEC2 positive expression was shown to be significantly correlated with recurrence and dormancy of SACC patients. CONCLUSIONS: These findings provide a novel insight into the role of DEC2 gene in tumor dormancy and metastasis.

Involvement of DNA methyltransferase 1 (DNMT1) and multidrug resistance-associated proteins in 2-methoxyestradiol-induced cytotoxicity in EC109/Taxol cells.

BACKGROUND: Due to acquired drug resistance, paclitaxel-based chemotherapy has limited clinical effects in the treatment of various tumors including esophageal cancer. This study analyzes the hypothesis that paclitaxel resistance is related to changes in the expression of DNA methyltransferase 1 (DNMT1). The thesis also studies multidrug resistance-related proteins and the mechanism underlying 2-methoxyestradiol (2-ME)-induced cytotoxicity in EC109/Taxol cells was examined. METHODS: In this study, the mechanisms of 2-ME-induced cytotoxicity in EC109/Taxol cells was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, DNA ladder assay, DNMT activity assay, and Western blotting. The result of 2-ME-induced cytotoxicity EC109/Taxol cells is compared with that of EC109 parental cells. RESULTS: The results show that low concentrations of 2-ME (0.5-10 µM) inhibited cell growth, with IC50 values of 2.04 and 5.38 µmol/L in EC109/Taxol cells and EC109 parental cells after 72 hours of treatment, respectively. Exposure to 2-ME could increase G2/M cell cycle arrest and could increase apoptosis more effectively in EC109/Taxol cells than that observed in the EC109 parental cells. Furthermore, it is observed that paclitaxel resistance is associated with decreased DNMT activity. This study shows that 2-ME decreases DNMT1-mediated paclitaxel resistance by simultaneously reducing the expression of ATP-binding cassette (ABC) transporters, including phosphoglycoprotein (P-gp), breast cancer resistance protein (BCRP), and multi-drug resistance protein 1 (MRP1), in EC109/Taxol cells. CONCLUSIONS: In this study, the co-treatment of Taxol and 2-ME to EC109 could significantly induce cytotoxic effects, whose mechanism might be associated with DNMT1 and multidrug resistance-associated proteins.