BRG1 promotes liver cancer cell proliferation and metastasis by enhancing mitochondrial function and ATP5A1 synthesis through TOMM40.

Hepatocellular carcinoma (HCC) is one of the most lethal malignant tumors worldwide. Brahma-related gene 1 (BRG1), as a catalytic ATPase, is a major regulator of gene expression and is known to mutate and overexpress in HCC. The purpose of this study was to investigate the mechanism of action of BRG1 in HCC cells. In our study, BRG1 was silenced or overexpressed in human HCC cell lines. Transwell and wound healing assays were used to analyze cell invasiveness and migration. Mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) detection were used to evaluate mitochondrial function in HCC cells. Colony formation and cell apoptosis assays were used to evaluate the effect of BRG1/TOMM40/ATP5A1 on HCC cell proliferation and apoptosis/death. Immunocytochemistry (ICC), immunofluorescence (IF) staining and western blot analysis were used to determine the effect of BRG1 on TOMM40, ATP5A1 pathway in HCC cells. As a result, knockdown of BRG1 significantly inhibited cell proliferation and invasion, promoted apoptosis in HCC cells, whereas BRG1 overexpression reversed the above effects. Overexpression of BRG1 can up-regulate MMP level, inhibit mPTP opening and activate TOMM40, ATP5A1 expression. Our results suggest that BRG1, as an oncogene, promotes HCC progression by regulating TOMM40 affecting mitochondrial function and ATP5A1 synthesis. Targeting BRG1 may represent a new and effective way to prevent HCC development.

Treatment of late left bronchopleural fistula after left pneumonectomy through right thoracic approach assisted by extracorporeal membrane oxygenation.

BACKGROUND: Bronchopleural fistula (BPF) is a rare but fatal complication after pneumonectomy. When a BPF occurs late (weeks to years postoperatively), direct resealing of the bronchial stump through the primary thoracic approach is challenging due to the risks of fibrothorax and injury to the pulmonary artery stump, and the surgical outcome is generally poor. Here, we report a case of late left BPF following left pneumonectomy successfully treated using a right thoracic approach assisted by extracorporeal membrane oxygenation (ECMO). CASE PRESENTATION: We report the case of a 57-year-old male patient who underwent left lower and left upper lobectomy, respectively, for heterochronic double primary lung cancer. A left BPF was diagnosed at the 22nd month postoperatively, and conservative treatment was ineffective. Finally, the left BPF was cured by minimally invasive BPF closure surgery via the right thoracic approach with the support of veno-venous extracorporeal membrane oxygenation (VV-ECMO). CONCLUSIONS: Advanced BPF following left pneumonectomy can be achieved with an individualized treatment plan, and the right thoracic approach assisted by ECMO is a relatively simple and effective method, which could be considered as an additional treatment option for similar patients.

Identification of a Novel CD8+ T cell exhaustion-related gene signature for predicting survival in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health concern, necessitating a deeper understanding of its prognosis and underlying mechanisms. This study aimed to investigate the mechanism and prognostic value of CD8+ T Cell exhaustion (CD8+ TEX)-related genes in HCC and construct a survival prognosis prediction model for patients with HCC. METHODS: CD8+ TEX-related genes associated with HCC prognosis were analysed and identified, and a prognostic prediction model was constructed using the 'least absolute shrinkage and selection operator' Cox regression model. Immunohistochemistry was used to verify the expression of the model genes in HCC tissues. A nomogram was constructed based on risk scores and clinical features, and its predictive efficacy was verified. The expression of STAM, ANXA5, and MAD2L2 in HCC cell lines was detected by western blotting; subsequently, these genes were knocked down in HCC cell lines by small interfering RNA, and their effects on the proliferation and migration of HCC cell lines were detected by colony formation assay, cck8, wound healing, and transwell assays. RESULTS: Six genes related to CD8+ TEX were included in the risk-prediction model. The prognosis of patients with HCC in the low-risk group was significantly better than that of those in the high-risk group. Cox regression analysis revealed that the risk score was an independent risk factor for the prognosis of patients with HCC. The differentially expressed genes in patients with high-risk HCC were mainly enriched in the nucleotide-binding oligomerization domain-containing protein-like receptor, hypoxia-inducible factor-1, and tumour programmed cell death protein (PD)-1/PD-L1 immune checkpoint pathways. The CD8+ TEX-related genes STAM, ANXA5, and MAD2L2 were knocked down in HCC cell lines to significantly inhibit cell proliferation and migration. The prediction results of the nomogram based on the risk score showed a good fit and application value. CONCLUSION: The prediction model based on CD8+ TEX-related genes can predict the prognosis of HCC and provide a theoretical basis for the early identification of patients with poor HCC prognosis.

Infection with COVID-19 promotes the progression of pancreatic cancer through the PI3K-AKT signaling pathway.

OBJECTIVE: To investigate the effect of COVID-19 infection on pancreatic cancer. METHODS: Based on the mRNA-Seq data of COVID-19 patients and pancreatic cancer (PC) patients in the GEO database, we used a support vector machine (SVM), LASSO-Cox regression analysis and random forest tree (RF) to screen the common signature genes of the two diseases and further investigate their effects and functional characteristics on PC, respectively. The above procedures were performed in R software. RESULTS: The proteins COL10A1/FAP/FN1 were found to be common signature genes for COVID-19 and PC, were significantly up-regulated in both diseases and showed good diagnostic efficacy for PC. The risk model based on COL10A1/FAP/FN1 showed good PC risk prediction ability and clinical application potential. Tumor typing based on COL10A1/FAP/FN1 expression levels effectively classified PC into different subtypes and showed significant differences between the two subtypes in terms of survival prognosis, immune levels, immune checkpoint expression levels, mutation status of common tumor mutation sites, and drug sensitivity analysis. While pathway analysis also revealed that FN1 as an extracellular matrix component may be involved in the biological process of PC by regulating the PI3K-AKT signaling axis. CONCLUSION: The upregulated expression of COL10A1/FAP/FN1, the characteristic genes of COVID-19, are potential diagnostic targets for PC, and the upregulated expression of FN1 may promote the progression of PC by activating the PI3K-AKT signaling pathway. The COL10A1/FAP/FN1-based typing provides a new typing approach for PC, and also provides a good reference and idea for the refinement of PC treatment and subsequent clinical research.

SIRT1 Inhibition-Induced Mitochondrial Damage Promotes GSDME-Dependent Pyroptosis in Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) is a malignant tumor that affects the liver and poses a significant threat to human health. Further investigation is necessary to fully understand the role of SIRT1, a protein linked to tumorigenesis, in HCC development. To investigate the effect of SIRT1 on HCC and elucidate the underlying mechanism. Eight pairs of HCC and paracancerous normal tissue specimens were collected. The levels of SIRT1 and GSDME in tissue samples were assessed using immunohistochemistry and western blotting. SIRT1 levels were determined in HCC (Huh7, HepG2, SNU-423, SNU-398, and HCCLM3) and L-02 cells using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. SNU-423 and HCCLM3 cells were transfected with si-SIRT1 and/or si-GSDME to knock down SIRT1 or GSDME expression. RT-qPCR and western blotting were performed to measure the expression of SIRT1, pro-casp-3, cl-casp-3, GSDME, GSDME-N, PGC-1α, Bax, and cytochrome c (Cyto C). Cell proliferation, migration, invasion, and apoptosis were assessed using the cell counting kit-8 (CCK-8), wound healing assay, Transwell invasion assay, and flow cytometry, respectively. The release of lactate dehydrogenase (LDH) was evaluated using an LDH kit. SIRT1 was upregulated in HCC tissues and cells, and a negative correlation was observed between SIRT1 and GSDME-N. SIRT1 silencing suppressed the proliferation, migration, and invasion of HCC cells while also promoting apoptosis and inducing mitochondrial damage. Additionally, the silencing of SIRT1 resulted in the formation of large bubbles on the plasma membrane of HCC cells, leading to cellular swelling and aggravated GSDME-dependent pyroptosis, resulting in an increase in LDH release. Inhibition of GSDME reduced SIRT1 silencing-induced cell swelling, decreased LDH release rate, and promoted apoptosis. SIRT1 silencing promotes GSDME-dependent pyroptosis in HCC cells by damaging mitochondria.

A Quasi-2D Polypyrrole Film with Band-Like Transport Behavior and High Charge-Carrier Mobility.

Quasi-2D (q2D) conjugated polymers (CPs) are polymers that consist of linear CP chains assembled through non-covalent interactions to form a layered structure. In this work, the synthesis of a novel crystalline q2D polypyrrole (q2DPPy) film at the air/H2 SO4 (95%) interface is reported. The unique interfacial environment facilitates chain extension, prevents disorder, and results in a crystalline, layered assembly of protonated quinoidal chains with a fully extended conformation in its crystalline domains. This unique structure features highly delocalized π-electron systems within the extended chains, which is responsible for the low effective mass and narrow electronic bandgap. Thus, the temperature-dependent charge-transport properties of q2DPPy are investigated using the van der Pauw (vdP) method and terahertz time-domain spectroscopy (THz-TDS). The vdP method reveals that the q2DPPy film exhibits a semiconducting behavior with a thermally activated hopping mechanism in long-range transport between the electrodes. Conversely, THz-TDS reveals a band-like transport, indicating intrinsic charge transport up to a record short-range high THz mobility of ≈107.1 cm2 V-1 s-1 .

Risk prediction for dermatomyositis-associated hepatocellular carcinoma.

OBJECTIVE: To explore dermatomyositis signature genes as potential biomarkers of hepatocellular carcinoma and their associated molecular regulatory mechanisms. METHODS: Based on the mRNA-Seq data of dermatomyositis and hepatocellular carcinoma in public databases, five dermatomyositis signature genes were screened by LASSO regression analysis and support vector machine (SVM) algorithm, and their biological functions in dermatomyositis with hepatocellular carcinoma were investigated, and a nomogram risk prediction model for hepatocellular carcinoma was constructed and its predictive efficiency was initially evaluated. The immune profile in hepatocellular carcinoma was examined based on the CIBERSORT and ssGSEA algorithms, and the correlation between five dermatomyositis signature genes and tumor immune cell infiltration and immune checkpoints in hepatocellular carcinoma was investigated. RESULTS: The expression levels of five dermatomyositis signature genes were significantly altered in hepatocellular carcinoma and showed good diagnostic efficacy for hepatocellular carcinoma, suggesting that they may be potential predictive targets for hepatocellular carcinoma, and the risk prediction model based on five dermatomyositis signature genes showed good risk prediction efficacy for hepatocellular carcinoma and has good potential for clinical application. In addition, we also found that the upregulation of SPP1 expression may activate the PI3K/ART signaling pathway through integrin-mediated activation, which in turn regulates the development and progression of hepatocellular carcinoma. CONCLUSION: LY6E, IFITM1, GADD45A, MT1M, and SPP1 are potential predictive targets for new-onset hepatocellular carcinoma in patients with dermatomyositis, and the upregulation of SPP1 expression may activate the PI3K/ART signaling pathway through the mediation of integrins to promote the development and progression of hepatocellular carcinoma.

Diagnosis of gastric cancer based on hybrid genes selection approach.

Gastric cancer (GC) is the third leading cause of cancer death worldwide. In the field of medicine, machine learning is widely used in genetic data mining and the construction of diagnostic models. This study proposed an intelligent model DERFS-XGBoost for rapid and accurate diagnosis of GC based on gene expression data. Firstly, the data of GC were collected and preprocessed. Secondly, ANOVA, t-test and fold chang (FC) were used to select genes that had significant differentially expressed genes (DEGs), and random forest (RF) was used to calculate their importance, and then sequential forward selection (SFS) was used to obtain the optimal feature subset. Finally, XGBoost was used for classification after synthetic minority oversampling technique (SMOTE) balanced between tumor and normal samples. In order to objectively evaluate the results, the 10-fold cross-validation and 10 repeated experiments were used in the experiment, and the average value of the evaluation indexes was used to evaluate the classification effect. Based on the experiment, DERFS-XGBoost model accuracy rate was 97.6%, precision was 100%, the recall rate was 97.3%, F1 was 99%, and the area under the ROC receiver operating characteristic curve AUC was 98.7%. The DERFS-XGBoost model has new characteristics which are different from existing diagnostic models, and has achieved a high classification effect with a small number of genes in comparison tests, which provides a new method and basis for the diagnosis of GC.

Abundant tannic acid modified gelatin/sodium alginate biocomposite hydrogels with high toughness, antifreezing, antioxidant and antibacterial properties.

The acidity of high tannic acid (TA) content solution can destroy the structure of protein, such as gelatin (G). This causes a big challenge to introduce abundant TA into the G-based hydrogels. Here, the G-based hydrogel system with abundant TA as hydrogen bonds provider was constructed by a "protective film" strategy. The protective film around the composite hydrogel was first formed by the chelation of sodium alginate (SA) and Ca2+. Subsequently, abundant TA and Ca2+ were successively introduced into the hydrogel system by immersing method. This strategy effectively protected the structure of the designed hydrogel. After treatment with 0.3 w/v TA and 0.06 w/v Ca2+ solutions, the tensile modulus, elongation at break and toughness of G/SA hydrogel increased about 4-, 2-, and 6-fold, respectively. Besides, G/SA-TA/Ca2+ hydrogels exhibited good water retention, anti-freezing, antioxidant, antibacterial properties and low hemolysis ratio. Cell experiments showed that G/SA-TA/Ca2+ hydrogels possessed good biocompatibility and could promote cell migration. Therefore, G/SA-TA/Ca2+ hydrogels are expected to be used in the field of biomedical engineering. The strategy proposed in this work also provides a new idea for improving the properties of other protein-based hydrogels.

Comparison of neoadjuvant chemoimmunotherapy and chemotherapy alone for resectable stage III non-small cell lung cancer: a real-world cohort study.

Background: We compared the real-world efficacy and safety of neoadjuvant chemoimmunotherapy to chemotherapy alone in patients with stage III non-small-cell lung cancer (NSCLC). Participants and methods: A total of 59 consecutive patients were finally selected and divided into two groups: the neoadjuvant chemotherapy group (n = 33) and the neoadjuvant chemoimmunotherapy group (n = 26). The primary endpoint was disease-free survival (DFS). The secondary endpoints were pathological response, clinical response, and adverse events. All patients were followed up to collect perioperative pathology and clinical data. Results: The objective response rate (ORR), pathological complete response (pCR), and major pathological response (MPR) were significantly higher in the neoadjuvant chemoimmunotherapy group than in the neoadjuvant chemotherapy group (73.1% vs. 45.5%, 34.6% vs. 3.0%, and 65.3% vs. 15.1%, respectively; P < 0.05). There was no statistically significant difference in disease-free survival between the neoadjuvant chemoimmunotherapy and neoadjuvant chemotherapy groups (P = 0.129). Patients in the neoadjuvant chemoimmunotherapy group had a higher rate of tumor regression than those in neoadjuvant chemotherapy group (37.0% [25 patients] vs. 29.0% [33 patients], P = 0.018). However, no discernible correlation between MPR achievement and the degree of tumor shrinkage was observed in either group (P > 0.05). The cumulative MPR rates were 42.3, 50, and 65.3% for 2, 3, and ≥ 4 cycles, respectively, in the neoadjuvant chemoimmunotherapy group and 9.1, 12.1, and 15.1% for ≤ 2, 3, and ≥ 4 cycles, respectively, in the neoadjuvant chemotherapy group. Moreover, No statistical difference was observed between the two groups regarding postoperative complications, resection range, operation time, surgical method, and extent of resection (P > 0.05). Although the incidence of grades III-IV adverse events was higher in the neoadjuvant chemotherapy group than in the neoadjuvant chemoimmunotherapy group (33.3% vs. 4.6%, P = 0.042), there was no significant difference in the incidence of adverse events between the two groups (64.6% vs. 83.6%, P = 0.072). Conclusion: In stage III NSCLC, neoadjuvant chemoimmunotherapy achieved higher pathological and clinical remission rates than chemotherapy alone, with compromising safety, making it an attractive choice for neoadjuvant therapy.

Nonalcoholic Fatty Liver Hepatocyte-Derived lncRNA MALAT1 Aggravates Pancreatic Cell Inflammation via the Inhibition of Autophagy by Upregulating YAP.

Background: Acute pancreatitis (AP) is one of the most common gastrointestinal disorders, which causes death with a high mortality rate of about 30%. The study aims to identify whether the nonalcoholic fatty liver disease (NAFLD)-derived lncRNA MALAT1 participates in the inflammation of pancreatic cell and its potential mechanism. Methods: The NAFLD cell model was constructed by treating HepG2 cells with FFA. The in vitro model of acute pancreatitis (AP) was established by the administration of caerulein on AR42J cells. MALAT1 and si-MALAT1 were transfected into pancreatic cells, and then exosomes were collected from the NAFLD cell model and then were cocultured with AR42J cells. Transmission electron microscopy was used to observe the morphology of exosomes. Oil Red O staining was applied to reveal the lipid deposition. The triglyceride, IL-6, and TNF-α levels were detected using ELISA. The MALAT1 level in exosomes was detected by qRT-PCR. The CD9, CD63, CD81, and CYP2E1, LC3II, and LC3I levels were detected by western blot. Results: MALAT1 was upregulated in NAFLD-derived exosomes and increased the levels of IL-6 and TNF-α in pancreatic cells. NAFLD-derived exosomes inhibited YAP phosphorylation, decreased the levels of IL-6 and TNF-α, and reduced the ratio of LC3II/LC3I protein in pancreatic cells. Silencing MALAT1 significantly returned the inhibitory effect of NAFLD on hippo-YAP pathway. YAP1 signal transduction inhibitor CA3 reversed the decrease of LC3II/LC3I expression and the increase of IL-6 and TNF-α levels induced by MALAT1 in the AP cell model. Conclusions: NAFLD-derived MALAT1 exacerbates pancreatic cell inflammation via inhibiting autophagy by upregulating YAP.

Pan-cancer analysis of the prognostic and immunological role of ANLN: An onco-immunological biomarker.

Anillin actin-binding protein (ANLN) is crucially involved in cell proliferation and migration. Moreover, ANLN is significantly in tumor progression in several types of human malignant tumors; however, it remains unclear whether ANLN acts through common molecular pathways within different tumor microenvironments, pathogeneses, prognoses and immunotherapy contexts. Therefore, this study aimed to perform bioinformatics analysis to examine the correlation of ANLN with tumor immune infiltration, immune evasion, tumor progression, immunotherapy, and tumor prognosis. We observed increased ANLN expression in multiple tumors, which could be involved in tumor cell proliferation, migration, infiltration, and prognosis. The level of ANLN methylation and genetic alteration was associated with prognosis in numerous tumors. ANLN facilitates tumor immune evasion through different mechanisms, which involve T-cell exclusion in different cancer types and tumor-infiltrating immune cells in colon adenocarcinoma, kidney renal clear cell carcinoma, liver hepatocellular carcinoma, and prostate adenocarcinoma. Additionally, ANLN is correlated with immune or chemotherapeutic outcomes in malignant cancers. Notably, ANLN expression may be a predictive biomarker for the response to immune checkpoint inhibitors. Taken together, our findings suggest that ANLN can be used as an onco-immunological biomarker and could serve as a hallmark for tumor screening, prognosis, individualized treatment design, and follow-up.

Clinical characteristics and antibodies against Echinococcus granulosus recombinant antigen P29 in patients with cystic echinococcosis in China.

OBJECTIVES: Cystic echinococcosis (CE) is a neglected parasitic zoonotic disease caused by the larval stage of the tapeworm Echinococcus granulosus (E. granulosus). This study aimed to understand the clinical characteristics of human CE in Ningxia Hui Autonomous Region (NHAR) located in northwest China and to investigate the antibody profiles against the recombinant E. granulosus antigen P29 (rEg.P29) in plasma of CE patients. METHODS: A total of 37 human CE patients, along with 37 healthy donors enrolled in this study and demographic and clinical data were analyzed, including age, gender, laboratory data, symptoms, and cysts description. Plasma levels of cytokines, total IgG, and total IgE were determined by sandwich ELISA kits. Specific antibodies against rEg.P29 and hydatid cyst fluid (HCF) were assessed by indirect ELISA. RESULTS: The results revealed that females have a higher percentage of CE patients than males. The incidence of CE reached a peak in the 41-50 years-old group. The liver was the most frequent location, accounting for 91.9%. Based on the CT images, cysts of 34 patients who had liver involvement, were classified as 1 (2.9%) CE1, 12 (35.3%) CE2, 5 (14.7%) CE3a, 1 (2.9%) CE3b, and 15 (44.2%) CE5. Twenty-nine (78.4%) patients had a single cyst and 8 (21.6%) had at least two cysts. The most frequently reported symptom was upper abdominal pain. The plasma level of IL-6 and total IgE were significantly increased in CE patients compared with healthy donors. Additionally, IgG response to rEg.P29 in CE patients was significantly higher than in healthy donors, and the dominant IgG subclass was IgG4. Further analysis of different patient groups revealed that rEg.P29-specific IgG and IgG4 were only elevated in CE patients with CE2 type cysts. CONCLUSIONS: This study systematically investigated the clinical characteristics of patients with CE and may provide a reference basis for the diagnosis and treatment of CE in NHAR. Furthermore, tests of specific IgG and IgG4 against rEg.P29 can be used as an assisted method for imaging techniques to identify cystic activity and determine the best therapeutic approach for CE.

A Cost-Effectiveness Analysis of Screening Strategies Involving Non-Invasive Prenatal Testing for Trisomy 21.

Introduction: In accordance with social development, the proportion of advanced maternal age (AMA) increased and the cost of non-invasive prenatal testing (NIPT) decreased. Objective: We aimed to investigate the benefits and cost-effectiveness of NIPT as primary or contingent strategies limited to the high-risk population of trisomy 21 (T21). Methods: Referring to parameters from publications or on-site verification, a theoretical model involving 1,000,000 single pregnancies was established. We presented five screening scenarios, primary NIPT (Strategy 1), contingent NIPT after traditional triple serum screening higher than 1/300 or 1/1,000 (Strategy 2-1 or 2-2), and age-based Strategy 3. Strategy 3 was stratified, with the following options: (1) for advanced maternal age (AMA) of 40 years and more, diagnostic testing was offered, (2) for AMA of 35-39 years, NIPT was introduced, (3) if younger than 35 years of age, contingent NIPT with risk higher than 1:300 (Strategy 3-1) or 1:1,000 (Strategy 3-2) will be offered. The primary outcome was an incremental cost analysis on the baseline and alternative assumptions, taking aging society, NIPT price, and compliance into consideration. The strategy was "appropriate" when the incremental cost was less than the cost of raising one T21 child (0.215 million US$). The second outcome included total cost, cost-effect, cost-benefit analysis, and screening efficiency. Results: Strategy1 was costly, while detecting most T21. Strategy 2-1 reduced unnecessary prenatal diagnosis (PD) and was optimal in total cost, cost-effect, and cost-benefit analysis, nevertheless, T21 detection was the least. Strategy 3 induced most of the PD procedures. Then, setting Strategy2-1 as a baseline for incremental cost analysis, Strategy 3-1 was appropriate. In sensitivity analysis, when the NIPT price was lower than 47 US$, Strategy 1 was the most appropriate. In a society with more than 20% of people older than 35 years of age, the incremental cost of Strategy 3-2 was proper. Conclusion: Combined strategies involving NIPT reduced unnecessary diagnostic tests. The AMA proportion and NIPT price played critical roles in the strategic decision. The age-based strategy was optimal in incremental cost analysis and was presented to be prominent as AMA proportion and NIPT acceptance increased. The primary NIPT was the most effective, but only at a certain price, it became the most cost-effective strategy.

MiR-495 Inhibits Cisplatin Resistance and Angiogenesis in Esophageal Cancer by Targeting ATP7A.

Background: Cancer resistance to chemotherapy is closely associated with changes in transporter systems. In this study, we investigated the possible regulation of 1 copper ion transporter (ATP7A; ATPase copper transporting alpha) by microRNA miR-495 and its implications in cisplatin resistance and angiogenesis in esophageal cancer. Methods: MiR-495 and ATP7A mRNA expression in clinical tissue samples and 2 cancer cell lines (Eca-109 and TE1) were detected by quantitative real-time polymerase chain reaction. The levels of miR-495 and ATP7A expression in Eca-109 and TE1 cells were increased by transfection with miR-495 mimics and ATP7A-overexpression vectors. Cell proliferation, apoptosis, and angiogenesis were assessed by CCK-8, flow cytometry, and tube formation assays, respectively. The levels of TNF-α and VEGF in cell culture supernatants were detected by enzyme linked immunosorbent assay, and in situ expression of NLRP3 was measured by immunofluorescence. The binding of miR-495 to ATP7A sequences was verified by dual luciferase reporter assays. Results:ATP7A expression was significantly increased, while miR-495 expression was decreased in the cancer tissues of esophageal cancer patients. MiR-495 mimics decreased the proliferation and promoted the apoptosis of cisplatin-resistant Eca-109 and TE1 cells. Furthermore, tube formation by human umbilical vein endothelial cells, TNF-α and VEGF secretion, and the levels of MRP1, ABCG1, ABCA1, and NLRP3 expression in cisplatin-resistant Eca-109 and TE1 cells were all reduced by miR-495 mimics. MiR-495 was shown to directly bind to ATP7A gene sequences to repress ATP7A expression in Eca-109 and TE1 cells. ATP7A overexpression substantially abrogated the changes in proliferation, apoptosis, angiogenesis, and above-mentioned gene expression in cisplatin-resistant Eca-109 and TE1 cells. Conclusions: MiR-495 suppressed cisplatin resistance and angiogenesis in esophageal cancer cells by targeting ATP7A gene expression.

ID1 mediates resistance to osimertinib in EGFR T790M-positive non-small cell lung cancer through epithelial-mesenchymal transition.

BACKGROUND: ID1 is associated with resistance to the first generation of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). However, the effect of ID1 expression on osimertinib resistance in EGFR T790M-positive NSCLC is not clear. METHODS: We established a drug-resistant cell line, H1975/OR, from the osimertinib-sensitive cell line H1975. Alterations in ID1 protein expression and Epithelial-mesenchymal transition (EMT)-related proteins were detected with western blot analysis. RT-PCR was used to evaluate the differences of gene mRNA levels. ID1 silencing and overexpression were used to investigate the effects of related gene on osimertinib resistance. Cell Counting Kit-8 (CCK8) was used to assess the proliferation rate in cells with altered of ID1 expression. Transwell assay was used to evaluate the invasion ability of different cells. The effects on the cell cycle and apoptosis were also compared using flow cytometry. RESULTS: In our study, we found that in osimertinib-resistant NSCLC cells, the expression level of the EMT-related protein E-cadherin was lower than that of sensitive cells, while the expression level of ID1 and vimentin were higher than those of sensitive cells. ID1 expression levels was closely related to E-cadherin and vimentin in both osimertinib-sensitive and resistant cells. Alteration of ID1 expression in H1975/OR cells could change the expression of E-cadherin. Downregulating ID1 expression in H1975/OR cells could inhibit cell proliferation, reduce cell invasion, promote cell apoptosis and arrested the cell cycle in the G1/G0 stage phase. Our study suggests that ID1 may induce EMT in EGFR T790M-positive NSCLC, which mediates drug resistance of osimertinib. CONCLUSIONS: Our study revealed the mechanism of ID1 mediated resistance to osimertinib in EGFR T790M-positive NSCLC through EMT, which may provide new ideas and methods for the treatment of EGFR mutated NSCLC after osimertinib resistance.

Platelet/lymphocyte ratio is a significant prognostic factor for targeted therapy in patients with EGFR-mutated non-small-cell lung cancer.

OBJECTIVE: To analyze the prognostic significance of the pretreatment platelet/lymphocyte ratio (PLR) for targeted therapy in patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). METHODS: We conducted a retrospective study of 96 patients with EGFR-mutated advanced NSCLC who were treated at Dongguan People's Hospital, Southern Medical University from May 2014 to December 2017. All patients received EGFR-targeted therapy until disease progression, unacceptable toxicity, or other factors. Approximately 3 days before the initial treatment, data including a detailed clinical history, physical examination, radiographic results, pathological diagnosis, and laboratory parameters including complete blood cell counts and albumin levels were evaluated. RESULTS: Patients in the PLR ≥ 190 group had shorter progression-free survival (PFS) than those in the PLR < 190 group. Furthermore, the 1-year PFS rate was worse in the PLR ≥ 190 group than in the PLR< 190 group. Multivariate analysis indicated the possible role of PLR as a prognostic factor for patients with advanced NSCLC who received EGFR-targeted therapy. CONCLUSIONS: Pretreatment PLR may be an independent prognostic factor for patients with NSCLC receiving EGFR tyrosine kinase inhibitor treatment. Further studies are needed to identify the impact of PLR on EGFR-mutated NSCLC.

Prognostic value of γ-glutamyl transpeptidase to albumin ratio combined with aspartate aminotransferase to lymphocyte ratio in patients with hepatocellular carcinoma after hepatectomy.

Hepatocellular carcinoma (HCC) is a malignant tumor associated with a high recurrence rate after hepatectomy. Recently, preoperative inflammatory and liver function reserve indices were found to predict increased risk of recurrence and decreased survival in HCC patients. This study aims to evaluate the ability of the γ-glutamyl transpeptidase-to-albumin ratio (GAR) and aspartate aminotransferase-to-lymphocyte ratio (ALRI), individually and in combination, to predict the prognosis of HCC patients after hepatectomy.We retrospectively reviewed 206 HCC patients who underwent radical resection at the General Hospital of Ningxia Medical University from January 2011 to November 2016. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value for GAR and ALRI. The Pearson Chi-Squared test was used to analyze the correlations between GAR, ALRI and clinicopathological characteristics. Univariate and multivariate analyses were used to determine the predictive value of these factors for disease-free survival (DFS) and overall survival (OS). Survival rates were drawn according to the Kaplan-Meier method and differences between subgroups were compared by the log-rank statistics.GAR and ALRI were significantly correlated with gender, history of smoking, prothrombin time, tumor diameter, T stage and early intrahepatic recurrence by the Pearson Chi-Squared test (all P < .05). Univariate analysis indicated that T stage, GAR and ALRI were significantly correlated with DFS and OS in HCC patients after hepatectomy. Multivariate analysis illustrated that GAR and ALRI were independently related to DFS and OS in HCC patients. Preoperative GAR > 0.946 or ALRI > 18.734 predicted poor prognosis in HCC patients after hepatectomy. Additionally, the predictive scope of GAR combined with ALRI was more sensitive than that of either individual measurement alone.Our data indicate that there is a close association between the clinicopathological characteristics in HCC patients and increased GAR or ALRI. Higher levels of GAR and ALRI could sensitively and specifically predict a poor prognosis in HCC patients after hepatectomy. Furthermore, combined usage of GAR and ALRI could improve the accuracy of this prediction.

Long noncoding RNA lnc-LOC645166 promotes adriamycin resistance via NF-κB/GATA3 axis in breast cancer.

Chemoresistance remains a significant obstacle for effective adriamycin (ADR) treatment in breast cancer. Recent efforts have revealed that long noncoding RNAs (lncRNAs) play a crucial role in cancer biology, including chemoresistance. We identified the lncRNA LOC645166 was upregulated in adriamycin resistant-breast cancer cells by Microarray analysis, which was further confirmed in the tissues of nonresponsive patients by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, and immunohistochemical assays. Downregulation of lncRNA LOC645166 increased cell sensitivity to adriamycin both in vitro and in vivo. In contrast, upregulation of lncRNA LOC645166 strengthened the tolerance of breast cancer cells to adriamycin. Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) demonstrated that lncRNA LOC645166 could increase the expression of GATA binding protein 3 (GATA3) via binding with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), leading to the activation of STAT3 and promoting chemoresistance in breast cancer. Together, the present study suggested that lncRNA LOC645166 mediated adriamycin chemoresistance in breast cancer by regulating GATA3 via NF-κB.

Icotinib is as efficacious as gefitinib for brain metastasis of EGFR mutated non-small-cell lung cancer.

BACKGROUND: The prognosis of non-small-cell lung cancer (NSCLC) with brain metastases is very poor. Currently, therapeutic methods for this patient population include whole-brain radiation therapy (WBRT), surgery, radiosurgery and systemic treatment. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) could be effective on cerebral metastases of mutated NSCLC. However, which EGFR-TKIs is more appropriate is still unknown. METHODS: We conducted a retrospective analysis of advanced NSCLC patients with brain metastases for EGFR targeted therapy from November 2013 to April 2018 at Dongguan People's Hospital, Southern Medical University, China. A total of 43 patients were recruit in this study. Among them, 21 cases received icotinib (125 mg, thrice a day) and 22 cases received gefitinib (250 mg, once a day) until disease progression or unacceptable toxicity. The primary end point of this study was intracranial PFS (iPFS). The relationships between therapeutic arms and patients characteristics were performed using Pearson's chi-square test or Fisher's exact test. The differences in PFS among the two arms were analyzed using Kaplan-Meier curves and log rank tests. RESULTS: There was no significant difference of intracranial ORR (66.6% versus 59.1%, P = 0.62) and DCR (85.7% versus 81.8%, P = 0.73) between the two arms. The median intracranial PFS (iPFS) for icotinib and gefitinib arms were 8.4 months (95% CI, 5.4 to 11.3 months) and 10.6 months (95% CI, 6.3 to 14.8 months), respectively (P = 0.17). Adverse events of the two study arms were generally mild. None of the patients experienced dose reduction of EGFR-TKIs. CONCLUSIONS: Our study showed that icotinib and gefitinib had similar efficacy for brain metastasis of EGFR mutated NSCLC. Large randomized studies are suggested to further illuminate the effect of these two EGFR-TKIs on cerebral lesions of NSCLC.