Plasma proteome profiling reveals dynamic of cholesterol marker after dual blocker therapy.

Dual blocker therapy (DBT) has the enhanced antitumor benefits than the monotherapy. Yet, few effective biomarkers are developed to monitor the therapy response. Herein, we investigate the DBT longitudinal plasma proteome profiling including 113 longitudinal samples from 22 patients who received anti-PD1 and anti-CTLA4 DBT therapy. The results show the immune response and cholesterol metabolism are upregulated after the first DBT cycle. Notably, the cholesterol metabolism is activated in the disease non-progressive group (DNP) during the therapy. Correspondingly, the clinical indicator prealbumin (PA), free triiodothyronine (FT3) and triiodothyronine (T3) show significantly positive association with the cholesterol metabolism. Furthermore, by integrating proteome and radiology approach, we observe the high-density lipoprotein partial remodeling are activated in DNP group and identify a candidate biomarker APOC3 that can reflect DBT response. Above, we establish a machine learning model to predict the DBT response and the model performance is validated by an independent cohort with balanced accuracy is 0.96. Thus, the plasma proteome profiling strategy evaluates the alteration of cholesterol metabolism and identifies a panel of biomarkers in DBT.

Intrapleural perfusion hyperthermia improves the efficiency of anti­PD1 antibody­based therapy for lung adenocarcinoma: A case report.

Chemotherapy based on intrapleural perfusion hyperthermia (IPH) can markedly improve the sensitivity of lung adenocarcinoma cells to anti-programmed cell death receptor 1 (PD1) antibody adjuvant chemotherapy and enhance the clinical response of a patient. In the present study, a unique case of a patient who failed to respond to immunotherapy combined with chemotherapy but achieved prolonged stable disease after treatment with IPH and subsequent sintilimab-based treatment, is reported. A 50-year-old Chinese female patient was admitted to a regional cancer hospital presenting with hemoptysis and persistent fever. The findings of computed tomography imaging and thoracic puncture tissue biopsy indicated a diagnosis of adenocarcinoma. The TNM and clinical stage were identified as cT2N3M0 and stage IIIB, respectively. Immunohistochemical tests showed the expression of programmed death-ligand 1 (PD-L1) with a tumor proportion score of 2%. No other classic genetic alterations were detected. Initially, sintilimab-based chemotherapy at 200 mg was administered, for three cycles from April 2020, and increased pleural effusion was observed on the left side. The best overall response (BOR) assessment of the local lesion was progressive disease. IPH combined with chemotherapy was then carried out from August to September 2020, after which the same course of sintilimab-based chemotherapy as aforementioned was provided from October 2020 to September 2023. The BOR evaluation results during the monotherapy courses were all judged as stable disease. Therefore, it was concluded that IPH can substantially improve the efficiency of anti-PD1 antibody-based therapy for lung adenocarcinoma.

Ultrahigh Energy Storage in Tungsten Bronze Dielectric Ceramics Through a Weakly Coupled Relaxor Design.

Dielectric energy-storage capacitors, known for their ultrafast discharge time and high-power density, find widespread applications in high-power pulse devices. However, ceramics featuring a tetragonal tungsten bronze structure (TTBs) have received limited attention due to their lower energy-storage capacity compared to perovskite counterparts. Herein, a TTBs relaxor ferroelectric ceramic based on the Gd0.03 Ba0.47 Sr0.485-1.5 x Smx Nb2 O6 composition, exhibiting an ultrahigh recoverable energy density of 9 J cm-3 and an efficiency of 84% under an electric field of 660 kV cm-1 is reported. Notably, the energy storage performance of this ceramic shows remarkable stability against frequency, temperature, and cycling electric field. The introduction of Sm3+ doping is found to create weakly coupled polar nanoregions in the Gd0.03 Ba0.47 Sr0.485 Nb2 O6 ceramic. Structural characterizations reveal that the incommensurability parameter increases with higher Sm3+ content, indicative of a highly disordered A-site structure. Simultaneously, the breakdown strength is also enhanced by raising the conduction activation energy, widening the bandgap, and reducing the electric field-induced strain. This work presents a significant improvement on the energy storage capabilities of TTBs-based capacitors, expanding the material choice for high-power pulse device applications.

High Throughput and Noninvasive Exosomal PD-L1 Detection for Accurate Immunotherapy Response Prediction via Tim4-Functionalized Magnetic Core-Shell Metal-Organic Frameworks.

Exosomal PD-L1 has been increasingly considered a noninvasive and accurate predictive marker for immunotherapy treatment response. However, the clinical monitoring of exosomal PD-L1 expression is still limited by its complex biological environment as well as the lack of a robust isolation strategy. Here, a Tim4-functionalized magnetic core-shell metal-organic framework (denoted as Fe3O4@SiO2-ILI-01@Tim4) was facilely constructed via layer-by-layer assembly. Owing to the strongly hydrophilic organic ligand of 1,3-bis(4-carboxybutyl)imidazolium bromide (ILI), magnetic Fe3O4@SiO2-ILI-01@Tim4 was endowed with the merits of low nonspecific adsorption and quick, easy, and convenient isolation of exosomes. The capture efficiency of Fe3O4@SiO2-ILI-01@Tim4 reached as high as 90.3 ± 0.5% and the recovery rate for exosomes was up to 93.0 ± 6.1%. The purity of the isolated exosomes was 7.5 times higher than that via the ultracentrifugation (UC) method. By further combination with immunofluorescence assay, high throughput and noninvasive exosomal PD-L1 detection for accurate immunotherapy response prediction was achieved. The prognosis accuracy of the developed Fe3O4@SiO2-ILI-01@Tim4-based strategy reached 85.7%, whereas the prognosis accuracy of the clinical gold standard, the PD-L1 combined positive score (CPS) test, was only 57.1%. Most interestingly, the developed method is especially suitable for those patients receiving false negative results in the CPS test. The proposed Fe3O4@SiO2-ILI-01@Tim4 is a highly efficient and robust technique showing great potential in high throughput and noninvasive exosomal PD-L1 detection for accurately predicting immunotherapy efficacy.

Two case reports of non-small cell lung cancer patients harboring acquired EGFR T790M-cis-C797S benefit from immune checkpoint inhibitor combined with platinum-based doublet chemotherapy.

Background: Acquired resistance is inevitable in non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). The emergence of EGFR exon 20 C797S is one of the major resistance mechanisms to osimertinib as a third-generation EGFR-TKI. To date, there is no standard of care for NSCLC patients after acquiring EGFR C797S. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various types of cancers in the last decade. Whether NSCLC patients with acquired EGFR C797S could benefit from ICIs remains elusive. Case Description: Herein, we reported two cases of EGFR-mutant NSCLC patients who acquired a tertiary EGFR mutation C797S benefited from ICIs. A 28-year-old woman presented with anepithymia and nausea. Chest computed tomography (CT) revealed a mass in the right lung. She was diagnosed with stage IV lung adenocarcinoma (LUAD) with EGFR exon 19 deletion (19del) based on imaging and next-generation sequencing (NGS) findings. She received icotinib followed by osimertinib, then acquired EGFR T790M-cis-C797S. She had low tumor mutation burden (TMB) and achieved partial response (PR) to a programmed cell death-1 (PD-1) inhibitor sintilimab combined with platinum-based doublet chemotherapy as late-line treatment lasting more than 5 months. A 66-year-old man complained with chest tightness, hemoptysis, and back pain. CT scans revealed a mass in the right lung and metastases to the bilateral lungs, liver, adrenal gland, mediastinal lymph nodes, and bone. He was also diagnosed with EGFR 19del-positive LUAD and treated with icotinib followed by osimertinib. He also acquired EGFR T790M-cis-C797S. The patient had low TMB also and benefited from a PD-1 inhibitor camrelizumab combined with platinum-based doublet chemotherapy as late-line treatment with a progression-free survival (PFS) of 8 months. Two cases had no treatment-related adverse events leading to discontinuation of PD-1 inhibitors. Conclusions: Our study provides the first clinical evidence that ICIs combined with platinum-based doublet chemotherapy may be effective treatment options for overcoming resistance mediated by EGFR T790M-cis-C797S. Clinical trials are needed to evaluate the efficacy and safety of PD-1 inhibitors in the treatment of NSCLC patients harboring EGFR T790M-cis-C797S.

Study on the Conduction Analysis and Blocking Intervention Scheme of Emotional Disorders between Cancer Patients and Their Families.

Objective: To analyze the transmission and blocking intervention scheme of emotional disorders between cancer patients and their families. Methods: About 150 patients with cancer and 150 family members with mood disorders treated in a tertiary hospital in North China from March 2021 to Octobor2021 were enrolled. The patients were randomly assigned into control group and study group. The control group received routine intervention, and the study group received the diagnosis, intervention, and treatment strategies of doctor-patient-affective disorder. The factors related to the transmission of emotional disorders between cancer patients and their families were analyzed, and the alterations of anxiety, depression, social support, and satisfaction of the two groups were compared under different blocking intervention schemes. Results: (1) Univariate analysis indicated that there were significant differences in family age, family income, sex, location of tumor, course of disease, TNM stage, somatic symptoms, and the incidence of anxiety and depression. There exhibited no significant difference between the gender of the family, the years of education of the family, the occupational status of the family, the relationship between the family and the patient, the mode of payment of the patient's medical expenses, the age of the patient, the mode of treatment of the patient, the degree of knowledge of the disease, and the incidence of anxiety and depression (P > 0.05). The anxiety and depression status of relatives were taken as dependent variables, and the age of family members, family income status, sex of patients, location of tumor, course of disease, TNM stage, and physical symptoms of patients were taken as independent variables, and the data were analyzed by Logistic regression analysis. Logistic regression analysis indicated that family income, tumor location, disease course, TNM stage, and somatic symptoms were the risk factors of anxiety and depression in relatives. (2) Comparison of social support status and intergroup, the objective support, subjective support, support utilization, and total score of social support in the study group were higher compared to the control group. In terms of the depression score before intervention, there exhibited no significant difference (P > 0.05), but after intervention, the depression score of the two groups decreased, and the depression score of the study group was lower compared to the control group before intervention, 1 week, 2 weeks, 3 weeks, and 4 weeks after intervention (P < 0.05). In terms of the anxiety score before intervention, there exhibited no significant difference (P > 0.05), but after intervention, the anxiety score of the two groups decreased, and the anxiety score of the study group was lower compared to the control group before intervention, 1 week, 2 weeks, 3 weeks, and 4 weeks after intervention (P < 0.05). Comparison of the satisfaction between the two groups and the study group was very satisfied in 56 cases, satisfactory in 14 cases, and general in 5 cases, and the satisfaction rate was 100.00%. The control group was very satisfied in 35 cases, satisfactory in 23 cases, general in 12 cases, and dissatisfied in 5 cases, and the satisfaction rate was 93.33%. The satisfaction of the study group was higher compared to the control group (P < 0.05). Conclusion: Family income, tumor location, course of disease, TNM stage, and somatic symptoms are the risk factors of anxiety and depression in relatives. After establishing the diagnosis, intervention and treatment strategies of doctor-patient-affective disorder, the emotional disorder of family members of cancer patients, is significantly promoted, and the intervention satisfaction is high, so the scheme is worth promoting.

The Effect of the Kirsten Rat Sarcoma Viral Oncogene Homolog (Kras) Proto-Oncogene, GTPase Genetic Polymorphism on the Safety and Efficacy of Bevacizumab Combination Treatment Regimens for Patients with Nonsquamous, Non-Small Cell Lung Cancer with Brain Metastases.

Background: Non-small cell lung cancer with brain metastasis (NSCLCBM) is normally observed in advanced-stage patients. Bevacizumab has shown to improve survival in the first-line treatment of metastatic brain NSCLC when added as a bolus plus irinotecan. However, a better understanding of the molecular mechanism is required to further drive progress in this field. Methods: A total of 155 patients were selected, including 42.10% with Kirsten rat sarcoma viral oncogene homolog (Kras)-mutant tumors. Of the 155 patients, 62.04% had developed brain metastasis (BM). Seven functional single-nucleotide polymorphisms (SNPs) in the Kras gene were extracted from the HapMap SNP database and were used for genotyping. The haplologit command in Statistical Software for Data Science (STATA) was used to model the association between haplotypes and case status. A Cox analysis was used to evaluate the prognostic value of the SNPs. Results: Among the patients treated with combination regimens, recurrence after local treatment was more frequent in those with two types of Kras mutations (odds ratio [OR] = 2.033 [0.5015-4.2552], p = 0.009). Among the patients with untreated BM, overall survival was shorter than that of patients with Kras mutations according to univariate analysis (OR = 5.130 [1.240-41.012], p = 0.033). Conclusions: Kras mutations have a predictive role for BM recurrence and outcome in patients with NSCLC treated with bevacizumab combination regimens.

Durable clinical benefit from afatinib in a lung adenocarcinoma patient with acquired EGFR L718V mutation-mediated resistance towards osimertinib: a case report and literature review.

Osimertinib, as a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), targeting EGFR exon 19 deletions, L858R, and T790M, has shown robust clinical efficacy and promising survival advantages in a subset of non-small cell lung cancer (NSCLC) patients. However, osimertinib-treated patients ultimately develop secondary resistance. Besides EGFR C797S mutation and EGFR amplification, a rare EGFR mutation, L718V, has been reported to confer osimertinib resistance in the literature, which is developed in about 8.0% of osimertinib-resistant NSCLC patients. Although the National Comprehensive Cancer Network or Chinese Society of Clinical Oncology NSCLC guidelines recommend radiotherapy, anti-angiogenesis therapy, chemotherapy and or immunotherapy for the treatment of NSCLC patients who acquire resistance to osimertinib, the feasible treatment options for patients harboring EGFR L718V remain elusive. There is an unmet need to develop effective strategies to treat EGFR L718X-positive NSCLC patients. Herein, we report that a lung adenocarcinoma patient with acquired EGFR L718V mutation-mediated resistance towards osimertinib derived durable response to the second-generation EGFR-TKI afatinib with a progression-free survival of 18 months and counting. Our work provides clinical evidence to administer afatinib in metastatic NSCLC patients who develop EGFR L718V at progression to osimertinib and paves the way for its potential clinical utilization.

LncRNA MCM3AP-AS1 Downregulates LncRNA MEG3 in Triple Negative Breast Cancer to Inhibit the Proliferation of Cancer Cells.

The oncogenic role of lncRNA MCM3AP-AS1 has been reported in several types of cancer, while its role in triple negative breast cancer (TNBC) is unknown. The expression levels of MCM3AP-AS1 and MEG3 in TNBC and paired nontumor tissues from 60 TNBC patients were measured by RT-qPCR. The effects of overexpression of MCM3AP-AS1 and MEG3 on the proliferation of BT-20 and BT-549 cells were evaluated by cell proliferation assay. We found that MCM3AP-AS1 was upregulated in TNBC, while lncRNA MEG3 was downregulated in TNBC, and they were inversely correlated with each other. In addition, the expression levels of MCM3AP-AS1 increased with the increase in tumor size, while the expression levels of MEG3 decreased with the increase in tumor size. In TNBC cells, overexpression of MCM3AP-AS1 led to downregulated expression of MEG3, while overexpression of MEG3 did not affect the expression of MCM3AP-AS1. Cell proliferation analysis showed that overexpression of MCM3AP-AS1 led to increased cell proliferation rate and reduced the inhibitory effects of overexpression of MEG3 on cancer cell proliferation. Therefore, MCM3AP-AS1 downregulates MEG3 in TNBC to inhibit the proliferation of cancer cells.

Profiling Oncogenic Germline Mutations in Unselected Chinese Lung Cancer Patients.

INTRODUCTION: Emerging evidence has suggested that inherited factors are also involved in lung cancer development. However, most studies focused on well-elucidated cancer predisposition genes, the majority of which are tumor suppressor genes. The profile of germline mutations in oncogenic driver genes remains unrevealed, which might also provide potential clinical implications for lung cancer management. METHODS: Sequencing data from 36,813 unselected lung cancer patients who underwent somatic mutation profiling were retrospectively reviewed. All recruited patients had matched white blood cell samples sequenced in parallel using a capture-based panel including eight key lung cancer driver genes (epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), MET proto-oncogene, receptor tyrosine kinase (MET), Kirsten rat sarcoma viral oncogene homolog (KRAS), Erb-B2 receptor tyrosine kinase 2(ERBB2), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), ret proto-oncogene (RET), and B-Raf proto-oncogene, serine/threonine kinase (BRAF)). Likely pathogenic/pathogenic (LP/P) variants were called according to the classification criteria of the American College of Medical Genetics and Genomics. Variants of uncertain significance (VUS) located in the kinase domains of driver genes and occurring recurrently (n ≥3) were also included for further analyses. RESULTS: Seven different LP/P variants in EGFR, MET, or RET were identified in 0.03% of lung cancer patients (n = 14) and 25 different VUS in the kinase domains of seven driver genes (except KRAS) were found with a prevalence of 0.3% (n = 117).Collectively, germline mutations were most frequently seen in ROS1 (n = 31, 0.084%), followed by MET (n = 23, 0.062%), EGFR (n = 22, 0.06%), ALK (n = 22, 0.06%) and RET (n = 17, 0.046%). LP/P variants and VUS fell the most commonly in EGFR (n = 10, 72%) and ROS1 (n = 31, 26%), respectively. Of the 10 patients with EGFR LP/P germline mutation, 70% also acquired somatic EGFR driver mutation exon21 p.L858R or exon19 deletion at baseline; while the three patients with pathogenic germline RET mutation displayed distinct baseline somatic profiles of rare EGFR mutation or KRAS exon2 p.G12C. We discovered 11 germline mutations that also occurred somatically, including four LP/P variants and seven VUS. CONCLUSION: We present the first study to systemically characterize the germline mutation in oncogenic driver genes in a large cohort of unselected patients with lung cancers.

Clinical Outcomes and Safety of Apatinib Mesylate in the Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer in Patients Who Progressed After Standard Therapy and Analysis of the KDR Gene Polymorphism.

PURPOSE: This study investigated the clinical outcomes and safety of apatinib mesylate in the treatment of advanced non-squamous non-small cell lung cancer (NSCLC) in patients who progressed after standard therapy, and analyzed the kinase insert domain receptor (KDR) gene polymorphism. METHODS: A total of 135 patients with advanced non-squamous NSCLC who received apatinib mesylate were included. Objective response rates were evaluated. Subsequently, progression-free survival (PFS) and overall survival (OS) were assessed and safety data were recorded. Additionally, peripheral blood and biopsy cancer tissue specimens were collected from the patients with NSCLC for the genotyping of the genetic polymorphism and mRNA expression of the KDR gene, respectively. Analysis on the association between genotypes and prognosis was conducted. RESULTS: The objective response rate of the 135 patients with NSCLC was 18.52%, disease control rate was 65.19%, median PFS was 3.95 months, and median OS was 10.05 months. Regarding the KDR gene polymorphism analysis, the distribution of the 4397T>C polymorphism genotypes was in accordance with the Hardy-Weinberg Equilibrium (P=0.868). Moreover, the prognosis analysis indicated that the median PFS of patients with the CC/TC and TT genotypes was 2.80 and 4.80 months, respectively (P=0.002). Furthermore, the median OS of patients with the two genotypes was 9.10 and 10.56 months, respectively (P=0.041). The multivariate Cox regression analysis showed that the TC/CC genotypes were an independent factor for PFS (odds ratio: 1.72, P=0.009). There was no correlation between the polymorphism and adverse reactions. Additionally, the mRNA expression analysis suggested that the mRNA levels of KDR in cancer tissues were significantly different between the TT and TC/CC genotypes (P<0.001). CONCLUSION: The clinical outcomes of treatment with apatinib mesylate for advanced non-squamous NSCLC in patients who progressed after standard therapy may be influenced by the KDR 4397T>C polymorphism through mediation of the mRNA expression of KDR.

Dynamic Ag-N Bond Enhanced Stretchable Conductor for Transparent and Self-Healing Electronic Skin.

Stretchable conductors have been achieved by stacking conductive nanomaterials onto the surfaces of elastomeric substrates. However, many of them show a dramatic decrease in conductivity under strain without an efficient way for the conductive layer to release strain. Here, we report a transparent, stretchable, and self-healing conductor with excellent mechanoelectrical stability by introducing dynamic bonding between conductive nanomaterials and an elastomeric substrate. We prepare the conductor by semiembedding Ag nanowires (AgNWs) into a self-healing polydimethylsiloxane (PDMS)-based elastomer, which is modified with bipyridine (Bpy) ligand and further cross-linked by adding Zn2+ as coordinator (Zn-Bpy-PDMS). The dynamic Ag-N bonds not only improve the wettability of the substrate and facilitate the spreading of AgNWs but also reversibly break and reform to accommodate the deformation of AgNWs. As a result, the resistance increase of Zn-Bpy-PDMS/AgNWs is much smaller than that without the dynamic bonding (PDMS/AgNWs). Besides, this conductor exhibits excellent conductivity (76.2 Ω/sq) and transparency (86.6% @ 550 nm), as well as extraordinary self-healing property with a low resistance increase (ΔR/R0 ∼ 1.4) after healing at room temperature for 1 day. This work provides insights into the future design of integrated electronic skin with transparency, stretchability, conductivity, and self-healing capability for applications in wearable optoelectronic devices.

Tanshinone IIA inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cells via p53-cyclin B1/CDC2.

Tanshinone IIA exhibits natural antioxidative and antineoplastic activity. However, to the best of our knowledge, the effects of tanshinone IIA on human nasopharyngeal carcinoma cells remains unknown. The present study aimed to investigate whether tanshinone IIA inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cells via p53-cyclin B1/cell division cycle gene 2 (CDC2). Cell proliferation, cytotoxicity and apoptosis of 13-9B cells were evaluated by an MTT assay, lactate dehydrogenase assay and flow cytometry, respectively. ELISA and western blot analysis were used to analyze caspase-3 activity and poly (ADP-ribose) polymerase (PARP), p53, cyclin B1 and CDC2 protein expression in 13-9B cells. Treatment of 13-9B cells with tanshinone IIA significantly suppressed cell proliferation and significantly induced cytotoxicity and apoptosis of 13-9B cells. Furthermore, tanshinone IIA significantly increased caspase-3 activity, and significantly increased the protein expression levels of PARP, p53, cyclin B1 and CDC2 in 13-9B cells. In summary, the current results indicate that tanshinone IIA inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cells via PARP, p53, cyclin B1/CDC2 and caspase-3-mediated signaling.

Endothelial growth factor receptor-targeted and reactive oxygen species-responsive lung cancer therapy by docetaxel and resveratrol encapsulated lipid-polymer hybrid nanoparticles.

Special targeted therapy like endothelial growth factor receptor (EGFR) targeted therapy is available for the treatment of advanced non-small cell lung cancer (NSCLC). Biodegradable core-shell lipid-polymer hybrid nanoparticles (LPNs) can combine the beneficial properties of lipid and polymeric NPs for controlled drug delivery. In the present study, epidermal growth factor (EGF) conjugated LPNs were fabricated to co-deliver docetaxel (DTX) and resveratrol (RSV). In vitro and in vivo studies demonstrated that EGF DTX/RSV LPNs have significant synergistic effects, best tumor inhibition ability and the lowest systemic toxicity. The results indicate that EGF DTX/RSV LPNs may be a promising strategy for treatment of NSCLC.

Inducible T-cell co-stimulators regulate the proliferation and invasion of human hepatocellular carcinoma HepG2 cells.

BACKGROUND: This study determined the regulatory effects of inducible T-cell co-stimulators (ICOS) in human hepatocellular carcinoma HepG2 cells using a RNA interference (RNAi) technique. METHODS: A RNAi technique was used to knockdown the expression of ICOS. ICOS expression after knockdown was detected as mRNA and protein levels by RT-PCR and Western blot, respectively. A MTT colorimetric assay was used to detect cell proliferation, and the Transwell assay was used to detect cell invasion. Western blot was carried out to detect the level of Bcl-2, AKT, and PI3K protein expression in different groups. RESULTS: The proliferation of HepG2 cells were significantly decreased after ICOS siRNA transfection (EG group). Similarly, the results of the Transwell experiment showed that invasion of HepG2 cells in the EG group was clearly reduced compared to the negative control (NC) and blank control groups (CON). Western blot analysis showed that knockdown of ICOS expression reduced the levels of Bcl-2 and AKT, and also significantly up-regulated the level of PI3K phosphorylation (P < 0.01). CONCLUSION: Down-regulating ICOS expression in HepG2 cells suppressed cell proliferation and invasion. The underlying mechanism may be related to the expression of the downstream factor, PI3K/AKT.

Inducible T-cell co-stimulators regulate the proliferation and invasion of human hepatocellular carcinoma HepG2 cells

Abstract Background This study determined the regulatory effects of inducible T-cell co-stimulators (ICOS) in human hepatocellular carcinoma HepG2 cells using a RNA interference (RNAi) technique. Methods A RNAi technique was used to knockdown the expression of ICOS. ICOS expression after knockdown was detected as mRNA and protein levels by RT-PCR and Western blot, respectively. A MTT colorimetric assay was used to detect cell proliferation, and the Transwell assay was used to detect cell invasion. Western blot was carried out to detect the level of Bcl-2, AKT, and PI3K protein expression in different groups. Results The proliferation of HepG2 cells were significantly decreased after ICOS siRNA transfection (EG group). Similarly, the results of the Transwell experiment showed that invasion of HepG2 cells in the EG group was clearly reduced compared to the negative control (NC) and blank control groups (CON). Western blot analysis showed that knockdown of ICOS expression reduced the levels of Bcl-2 and AKT, and also significantly up-regulated the level of PI3K phosphorylation (P < 0.01). Conclusion Down-regulating ICOS expression in HepG2 cells suppressed cell proliferation and invasion. The underlying mechanism may be related to the expression of the downstream factor, PI3K/AKT.

Up-Regulated Expression of SPRY4-IT1 Predicts Poor Prognosis in Colorectal Cancer.

BACKGROUND Long non-coding RNA SPRY4 intronic transcript 1 (lncRNA SPRY4-IT1) has been reported to be associated with the progression of several cancers, but its expression level in colorectal cancer (CRC) has rarely been reported. The purpose of this study was to estimate the clinical significance of SPRY4-IT1 in CRC. MATERIAL AND METHODS The relative expression levels of SPRY4-IT1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in diseased tissues and the adjacent normal tissues of 106 CRC patients. Chi-square method was used to evaluate the association between SPRY4-IT1 expression and the clinical features. Additionally, we assessed the overall survival at different expression levels of SPRY4-IT1 using Kaplan-Meier method. The prognostic significance of SPRY4-IT1 was estimated by Cox regression analysis. RESULTS Up-regulated level of SPRY4-IT1 was detected in pathologic tissues of CRC patients compared with adjacent normal tissues (P=0.000). The relative expression of SPRY4-IT1 was associated with the tumor size, the depth of invasion, lymph node invasion, distant invasion, and tumor stage (P<0.05). Patients with high expression of SPRY4-IT1 had poor overall survival compared with those with high level (39.3 vs. 49.3 months, log-rank test, P=0.016). Cox regression analysis showed that SPRY4-IT1 could act as an independent prognostic factor in CRC (HR=2.341, 95% CI=1.136-4.826, P=0.021). CONCLUSIONS SPRY4-IT1 might be associated with tumorigenesis and progression of CRC, and it may be a promising biomarker for prognosis in patients with CRC.

The de Winter electrocardiographic pattern of proximal left anterior descending occlusion.

Prompt recognition of electrocardiographic signs of acute left anterior descending (LAD) occlusion is essential for timely restoration of flow. However, some patients may present with atypical electrocardiographic signs, and early diagnosis of these patients may constitute a clinical challenge. Here, we report two cases presenting with an atypical electrocardiographic manifestation despite angiographically confirmed acute thrombotic occlusion of proximal LAD. These cases highlight the importance of recognizing the de Winter electrocardiogram pattern in cases of suspected acute myocardial infarction (AMI). An emergency percutaneous coronary intervention (PCI) should be performed in suspected AMI patients as early as possible.

MicroRNA-146a rs2910164 polymorphism is associated with susceptibility to non-small cell lung cancer in the Chinese population.

The aim of the present study was to investigate the association of single nucleotide polymorphisms (SNP) of the microRNA-146a (miR-146a) genes with the risk of nonsmall cell lung cancer (NSCLC). The genotyping of miR-146a rs2910164 polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that CC genotype and C allele distribution in the NSCLC patient were significantly higher than that of the controls (P=0.03 and 0.03, respectively). No significant differences were found between the two subgroups when stratified by clinical characteristics including age, sexual, smoke status, histological type, lymph node metastasis and clinical stage. In addition, the expression of miR-146a was detected by the Taqman real-time PCR. It demonstrated that the miR-146a expression was significantly decreased in NSCLC patients compared with that of nonmalignant lung tissues (P=0.01). In addition, the miR-146a expression of CC genotypes subgroup was significantly decreased than of GC/GG genotype subgroup in tumor tissues (P=0.0022). It confirmed that the SNP rs2910164 could functionally affect the miR-146a expression levels. In conclusion, it showed that the rs2910164 polymorphism of miR-146a is associated with the risk of NSCLC in the Chinese population.