MiRNA-296-5p promotes the sensitivity of nasopharyngeal carcinoma cells to cisplatin via targeted inhibition of STAT3/KLF4 signaling axis.

Improving drug sensitivity is an important strategy in chemotherapy of cancer and accumulating evidence indicates that miRNAs are involved in the regulation of drug sensitivity, but the specific mechanism is still unclear. Our previous study has found that miR-296-5p was significantly downregulated in nasopharyngeal carcinoma (NPC). Here, we aim to explore whether miR-296-5p is involved in regulating cisplatin sensitivity in NPC by regulating STAT3/KLF4 signaling axis. The cell proliferation and clonogenic capacity of NPC cells were evaluated by CCK8 Assay and plate colony assay, respectively. The Annexin V-FITC staining kit was used to determine and quantify the apoptotic cells using flow cytometry. The drug efflux ability of NPC cells were determined by Rhodamine 123 efflux experiment. The expression of miR-296-5p, apoptosis-related genes and protein in NPC cell lines were detected by qPCR and Western blot, respectively. Animal study was used to evaluate the sensitivity of NPC cells to DDP treatment in vivo. Our results showed that elevated miR-296-5p expression obviously promoted the sensitivity of NPC cells to DDP by inhibiting cell proliferation and clonogenic capacity, and inducing apoptosis. In addition, we found that miR-296-5p inhibited the expression of STAT3 and KLF4 in NPC cells, while overexpression of exogenous STAT3 reversed miR-296-5p-mediated enhancement in cell death of DDP-treated NPC cells. In vivo studies further confirmed that miR-296-5p promotes the sensitivity of NPC cells to DDP treatment. miRNA-296-5p enhances the drug sensitivity of nasopharyngeal carcinoma cells to cisplatin via STAT3/KLF4 signaling pathway.

Licochalcone A induces endoplasmic reticulum stress-mediated apoptosis of endometrial cancer cells via upregulation of GRP78 expression.

Licochalcone A (LicA), a natural compound extracted from licorice root, has been shown to exert a variety of anticancer activities. Whether LicA has such effects on endometrial cancer (EMC) is unclear. This study aims to investigate the antitumor effects of LicA on EMC. Our results show that LicA significantly reduced the viability and induced apoptosis of EMC cells and EMC-7 cells from EMC patients. LicA was also found to induce endoplasmic reticulum (ER) stress, leading to increased expression of ER-related proteins (GRP78/PERK/IRE1α/CHOP) in EMC cell lines. Suppression of GRP78 expression in human EMC cells treated with LicA significantly attenuated the effects of LicA, resulting in reduced ER-stress mediated cell apoptosis and decreased expression of ER- and apoptosis-related proteins. Our findings demonstrate that LicA induces apoptosis in EMC cells through the GRP78-mediated ER-stress pathway, emphasizing the potential of LicA as an anticancer therapy for EMC.

[Application of Modified DTT Methods to Reduce the Interference of Daratumumab on Serological Detection].

OBJECTIVE: To modified the classic dithiothreitol (DTT) method for treating red blood cells (RBCs) in Technical Manual of American Association of Blood Banks（AABB） and evaluate its application value in pre-transfusion examination of patients treated with daratumumab. METHODS: The classic 0.2 mol/L DTT method was improved in terms of PBS, DTT concentration, donor RBCs concentration (suspended/packed) and sample processing time. The modified DTT methods and AABB classic DTT method were applied to the blood matching tests of 12 multiple myeloma patients treated with daratumumab. The effect of treating panel RBCs with modified DTT methods on the detection of other irregular antibodies was evaluated by using antiserum and antibody reagents with known antibody properties. RESULTS: Two modified DTT methods were established (method 1: changed the concentration of DTT to 0.01 mol/L; method 2: changed the concentration of DTT to 0.02 mol/L and replaced the packed RBCs with 3% RBCs suspension). The optimal treatment time was 35 min for the modified DTT methods. At this time, the pan-agglutination caused by daratumumab was eliminated, but the detection of antibodies such as anti-E, anti-JKa, anti-M were not affected, and the titer of anti-K antibodies was only slightly decreased. CONCLUSION: The modified DTT methods were effective, which can eliminate the interference of daratumumab while retaining the activity of the Kell blood group system, and can replace the current classic DTT method in AABB Technical Manual.

Targeting of Mcl-1 Expression by MiRNA-3614-5p Promotes Cell Apoptosis of Human Prostate Cancer Cells.

MicroRNA (miRNA) acts as a critical regulator of growth in various human malignancies. However, the role of miRNA-3614 in the progression of human prostate cancer remains unknown. In this study, our results demonstrated that miRNA-3614-5p exerts a significant inhibitory effect on cell viability and colony formation and induces sub-G1 cell cycle arrest and apoptosis in human prostate cancer cells. Myeloid cell leukemia-1 (Mcl-1) acts as a master regulator of cell survival. Using the miRNA databases, miRNA-3614-5p was found to regulate Mcl-1 expression by targeting positions of the Mcl-1-3' UTR. The reduction of Mcl-1 expression by miRNA-3614-5p was further confirmed using an immunoblotting assay. Pro-apoptotic caspase-3 and poly (ADP-ribose) polymerase (PARP) were significantly activated by miRNA-3614-5p to generate cleaved caspase-3 (active caspase-3) and cleaved PARP (active PARP), accompanied by the inhibited Mcl-1 expression. These findings were the first to demonstrate the anti-growth effects of miRNA-3614-5p through downregulating Mcl-1 expression in human prostate cancer cells.

Norcantharidin combined with paclitaxel induces endoplasmic reticulum stress mediated apoptotic effect in prostate cancer cells by targeting SIRT7 expression.

Prostate cancer (PCa), an extremely common malignancy in males, is the most prevalent disease in several countries. Norcantharidin (NCTD) has antiproliferation, antimetastasis, apoptosis, and autophagy effects in various tumor cells. Nevertheless, the antitumor effect of NCTD combined with paclitaxel (PTX), a chemotherapeutic drug, in PCa remains unknown. The cell growth, proliferative rate, cell cycle distribution, and cell death were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, colony formation assay, PI staining, and Annexin V/PI staining by flow cytomertry, whereas the mitochondrial membrane potential (MMP) and endoplasmic reticulum (ER) stress was evaluated using the MitoPotential assay and ER-ID red assay. We also evaluated the protein and mRNA expression of SIRTs by Western blotting and qRTPCR assay. Overexpression effectivity was measured by DNA transfection assay. Our study showed that cell viability and proliferative PC3 and DU145 rates were effectively inhibited after NCTD-PTX combination. We also found that NCTD-PTX combination treatment significantly enhance G2/M phase arrest, induction of cell death and ER stress, loss of MMP, and ER- or apoptotic-related protein expression. Furthermore, NCTD-PTX combination treatment was significantly decreasing the protein and mRNA expression of SIRT7 in PCa cells. Combination therapy effectively reduced cell viability, ER stress-mediated apoptosis and p-eIF2α/ATF4/CHOP/cleaved-PARP expression inhibition in SIRT7 overexpression of PCa cells. These results indicate that NCTD combined with PTX induces ER stress-mediated apoptosis of PCa cells by regulating the SIRT7 expression axis. Moreover, combination therapy may become a potential therapeutic strategy against human PCa.

Gelatin/Chitosan Bilayer Patches Loaded with Cortex Phellodendron amurense/Centella asiatica Extracts for Anti-Acne Application.

Acne is a chronic inflammatory skin disease that often occurs with anaerobic Propionibacterium acnes (P. acnes). Anti-acne patches, made of hydrocolloid or hydrogel, have become a popular way of topical treatment. The outer water-impermeable layer of commercial patches might create hypoxic conditions and promote P. acnes growth. In this study, gelatin/chitosan (GC) bilayer patches were prepared at different temperatures that included room temperature (RT), -20 °C/RT, and -80 °C/RT. The most promising GC bilayer patch (-80 °C /RT) contained a dense upper layer for protection from bacteria and infection and a porous lower layer for absorbing pus and fluids from pimples. The anti-acne bilayer patch was loaded with Cortex Phellodendri amurensis (PA) and Centella asiatica (CA) extracts. PA extract could inhibit the growth of P. acnes and CA extract was reported to improve wound healing and reduce scar formation. Moreover, the water retention rate, weight loss rate, antibacterial activity, and in vitro cytotoxicity of the patches were investigated. The porous structure of the patches promoted water retention and contributed to absorbing the exudate when used on open acne wounds. The GC bilayer patches loaded with PA/CA extracts were demonstrated to inhibit the growth of P. acnes, and accelerate the skin fibroblast cell viability. Based on their activities and characteristics, the GC bilayer patches with PA/CA extract prepared at -80 °C/RT obtain the potential for the application of acne spot treatment.

Novel strategy for food safety risk management and communication: Risk identification for benzoic acid residues in pickled vegetables.

Benzoic acid (BA) is widely used as an antimicrobial preservative to prolong the shelf-life of pickled vegetables. A method for rapidly determining the BA content in forty pickled vegetable samples was developed by coupling ultrasonic extraction with surface-enhanced Raman scattering (SERS) and an adaptive iteratively reweighted penalized least-squares (AirPLS) algorithm. The results obtained with this method were compared and correlated with those from high-performance liquid chromatography measurements. Amplification of the Raman scattering via the SERS effect was induced by gold nanoparticles (AuNPs) when BA was irradiated with a 785 nm laser. The AirPLS algorithm was used to reduce the background interference signal, which was also amplified. The amplified Raman scattering effect of BA in the pickled vegetables displayed a positive and significant correlation with the HPLC concentration of BA, with high reproducibility. For HPLC determination of the concentration of BA in the range of 0-820 ppm, the BA monomer's intensity of the 944-1,005 cm-1 and 1,366-1,373 cm-1 peaks, and BA dimer's intensity of the 1,025 cm-1 and 1,465-1,482 cm-1 peaks in the SERS spectrum were respectively converted to the Z-ratio BA monomer and Z-ratio BA dimer standard scores by Z-Score conversion. The sum's (Z-ratio BA monomer + Z-ratio BA dimer) sensitivity was 100%, and specificity was 90.9% by receiver operating characteristic curve. This study found that a Raman spectroscopy-based monitoring method can be one of the fastest screening inspection options that can complete an analysis within a short period of time and produce reliable results. This approach is particularly cost-effective, which makes it suitable for the initial screening of raw materials and provides an effective management strategy easy to communicate with food safety officials.

Determinants of the Public Health Promotion Behavior: Evidence from Repurchasing Health Foods for Improving Gastrointestinal Tract Functions.

Researchers believe that health foods can promote health and that the consumption of health foods can effectively help people to maintain their health. This study mainly adopted the health belief model (HBM) integrated with perceived behavioral control to investigate the repurchase behavior of consumers with regard to health foods that improve gastrointestinal functions. We obtained 550 valid questionnaires from consumers who had purchased gastrointestinal health foods and conducted structural equation modeling. Results from our analysis revealed that perceived susceptibility, perceived severity, perceived benefits of action, and perceived behavioral control exert a positive influence on repurchase intention and that perceived barriers of action exerts a negative influence on repurchase intention. Furthermore, repurchase intention was found to have a positive impact on repurchase behavior. The results of this study can be used as a reference for health food marketing strategies and public health behavior promotions.

Silencing PROK2 Inhibits Invasion of Human Cervical Cancer Cells by Targeting MMP15 Expression.

Cervical cancer is the second most frequent type of gynecologic cancer worldwide. Prokineticin 2 (PROK2) is reported to be involved in tumor progression in some malignant tumors. However, the role of PROK2 in the development of cervical cancer remains unknown. Our results indicate that PROK2 is overexpressed in the human cervical cancer. Cervical cancer patients with high PROK2 expression have a shorter overall survival rate (OS) and disease-free survival rate (DFS). PROK2 acts as a potential biomarker for predicting OS and DFS of cervical cancer patients. We further show that PROK2 is important factor for oncogenic migration and invasion in human cervical cancer cells. Knockdown PROK2 significantly inhibited cell migration, invasion, and MMP15 protein expression in HeLa cells. High expression of MMP15 is confirmed in the human cervical cancer, is significantly associated with the shorter overall survival rate (OS) and is correlated with PROK2 expression. Overexpression of PROK2 using PROK2 plasmid significantly reverses the function of knockdown PROK2, and further upregulates MMP15 expression, migration and invasion of human cervical cancer cells. In conclusion, our findings are the first to demonstrate the role of PROK2 as a novel and potential biomarker for clinical use, and reveal the oncogenic functions of PROK2 as therapeutic target for cervical cancer.

PD-L1 expression level in different thymoma stages and thymic carcinoma: a meta-analysis.

BACKGROUND: The immune checkpoint ligand, programmed cell death 1 ligand 1 (PD-L1), is expressed in various tumors and associated with response to drugs that target programmed cell death protein 1. Previous studies have estimated the level of PD-L1 expression among different stages of thymoma and thymic carcinoma to evaluate its potential use as a diagnostic factor; however, its varying expression level has been problematic. We conducted this meta-analysis of published literature to evaluate PD-L1 expression in thymomas and thymic carcinomas. METHODS: We analyzed 12 studies that included 320 patients with type A/AB/B1 thymoma, 225 patients with type B2/B3 thymoma, and 180 patients with thymic carcinoma. RESULTS: No difference in PD-L1 expression level was found between the B2/B3 vs C groups (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.26, 1.76; p = 0.42). However, the heterogeneity was very high (I2 = 78%), and a significant difference was found between groups A/AB/B1 and B2/B3 (OR, 0.22; 95% CI, 0.12, 0.41; p < 0.001), with a relatively low heterogeneity (I2 = 55%). CONCLUSION: PD-L1 positivity might be a useful factor to differentiate type A/AB/B1 thymoma from type B2/B3 and thymic carcinoma. This result might be valuable for potential anti PD-L1 treatment in thymoma and thymic carcinoma.

Synergistic antimetastatic effect of cotreatment with licochalcone A and sorafenib on human hepatocellular carcinoma cells through the inactivation of MKK4/JNK and uPA expression.

To improve the clinical outcome of tumor chemotherapy, more effective combination treatments against tumor metastasis and recurrence are required. Licochalcone A (LicA) is the root of Glycyrrhiza inflata and has been reported to possess anti-inflammatory, antimicrobial, and antitumor effects. Sorafenib (Sor), a multikinase inhibitor, is used to treat patients with solid tumors such as advanced hepatocellular carcinoma (HCC). However, the synergistic effects of LicA and Sor on the metastasis of human HCC cells have not been reported. We found that LicA and Sor did not have cytotoxic effects or arrest growth in human SK-Hep-1 and Huh-7 cells. In addition, treatment with LicA or Sor alone inhibited migration and invasion in human SK-Hep-1 and Huh-7 HCC cells. Furthermore, cotreatment with LicA and Sor synergistically inhibited the migration and invasion of HCC cells and significantly inhibited uPA protein expression. Notably, cotreatment of LicA and Sor synergistically and significantly downregulated MKK4-JNK expression. Through tail vein injection in nude mice, the aforementioned cotreatment synergistically suppressed SK-Hep-1 cell-mediated lung metastasis. These findings first revealed the synergistic effects of LicA and Sor cotreatment against human HCC cells, further suggesting that beneficial effects on tumor regression could be confirmed through prospective clinical trials.

Induction of endoplasmic reticulum stress and mitochondrial dysfunction dependent apoptosis signaling pathway in human renal cancer cells by norcantharidin.

Previous studies reported that norcantharidin (NCTD) has anti-tumor effects. We investigated the antitumor effects and underlying mechanism of NCTD on human renal cancer in vitro and in vivo. NCTD significantly decreased renal cancer cell viability by induction of apoptosis, as determined by the MTT assay and annexin V/PI staining. NCTD treatment of 786-O and A-498 cells altered the expression of caspase family proteins and PARP. Moreover, NCTD induced mitochondrial depolarization, which was accompanied by an increased level of Bax and decreased levels of Bcl-2 and Mcl-1. NCTD induced endoplasmic reticulum (ER) stress by increasing the expression of Grp78, p-elF2α, ATF4, and CHOP. Pretreatment with an ER stress inhibitor (salubrinal) significantly attenuated the effect of NCTD. NCTD also induced activation of the AKT pathway in 786-O and A-498 cells. Overexpression of AKT partly reversed the effect of NCTD on apoptosis. NCTD treatment led to decreased expression of Bcl-2 and Mcl-1, and increased expression of Bax, cleaved-caspase-9, cleaved-PARP, and p-elF2α. Our in vivo studies demonstrated that NCTD significantly inhibited tumor growth in a nude mouse xenograft model. Taken together, our results suggest that NCTD is a potential anti-tumor agent for treatment of renal carcinoma.

Praeruptorin A Inhibits Human Cervical Cancer Cell Growth and Invasion by Suppressing MMP-2 Expression and ERK1/2 Signaling.

Praeruptorin A (PA) is a pyranocumarin present in the dried root of Peucedanumpraeruptorum Dunn that has anticancer effects against several types of cells. However, the effect of PA on human cervical cancer cells is unknown. Our results indicate that PA significantly inhibited cell proliferation, colony formation, migration, invasion, and wound closure of HeLa and SiHa cells, induced cell cycle arrest at G0/G1 phase, upregulated Rb, p16, p21 and p27 proteins and downregulated cyclin D1 and S-phase kinase-associated protein 2 (Skp2) proteins. PA also significantly reduced expression of matrix metalloproteinase-2 (MMP-2) and increased expression of tissue inhibitor of metalloproteinase-2 (TIMP-2). In addition, PA suppressed ERK1/2 activation and increased the effect of PD98059 (a specific MEK1/2 inhibitor) in downregulation of MMP-2 and upregulation of TIMP-2. PA treatment inhibited the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on upregulation of ERK1/2 activation, MMP-2 expression, cellular migration, and invasion of HeLa cells. Our findings are the first to demonstrate the activity of PA against cervical cancer cells, and suggest this agent has promise as a therapeutic agent in treatment of human cervical cancer.

[Residue Concentration and Distribution Characteristics of Perfluorinated Compounds in Surface Water from Qiantang River in Hangzhou Section].

This study studied the pollution characteristics of perfluorinated compounds (PFCs) in Qiantang River in Hangzhou section (QR). Surface water samples, collected in July 2014 and January 2015 from 14 sites in QR were analyzed for 16 PFCs. All samples were prepared by solid-phase extraction with Oasis WAX cartridges and analyzed using the ultra performance liquid chromatography interfaced to tandem mass spectrometry ( UPLC-MS/MS). The results showed that 8 medium-and short-chain PFCs including C4 and C8 perfluorinated sulfonates (PFSAs) and C4-C9 perfluorinated carboxylic acids (PFCAs) were detected in the surface waters. The total concentrations of PFCs ranged from 0.98 to 609 ng · L⁻¹, while perfluorooctanoic acid (PFOA) dominated, with range of 0.59-538 ng L⁻¹, and perfluorooctane sulfonate (PFOS) was detected at lower levels, ranging from 0 to 2.48 ng · L⁻¹. The spatial distribution of PFCs varied, and the pollutant concentrations at the sampling sites located in upstream of the river such as Lanjiangkou and Jiangjunyan were relatively high, PFCs concentration showed a decreasing trend from the upstream to the downstream. According to the ratio of feature components, PFCs in surface water of QR originated largely from the input of direct sewage emissions. Taken together, the PFCs pollution was highly correlated with the upstream of Qiantang River valley's industry distribution, and most of the mass load in the investigated river was attributed to upstream running water with a minor influence from the wastewater discharges along the river basin. Overall, the results presented here indicated that greater attention should be given to the contamination of PFCs, especially for PFOA in water body of QR.

Can we accredit hospital ethics? A tentative proposal.

OBJECTIVES: The objective of this research was to develop ethics accreditation standards for hospitals. RESEARCH DESIGN: Our research methods included a literature review, an expert focus group, the Delphi technique and a hospital survey. The entire process was separated into two stages: (1) the development of a draft of hospital ethics accreditation standards; and (2) conducting a nationwide hospital survey of the proposed standards. RESULTS: This study produced a tentative draft of hospital ethics accreditation standards comprised of six chapters and 62 standards based on the expert focus group and Delphi technique. The six chapters are: Medical ethics policies, regulations and leadership; The establishment and operation of a medical ethics committee; The establishment and operation of research-related ethics committees; Medical ethics education; Organisational ethical climate; and Respect for patients' rights and establishment of good hospital-patient relationships. The hospital survey indicated that the concept of an organisational ethical climate was new to most hospital managers, most hospitals disliked the idea of having a separate hospital ethics accreditation system, and small hospitals were concerned about their ability to comply with all of the standards. CONCLUSIONS: Regardless of whether hospital ethics accreditation can be a stand-alone accreditation or just part of existing hospital accreditation programmes, we hope this draft can serve as a good reference for future endeavours by hospital accreditation authorities.

Effects of a JAK inhibitor, AG490, on proliferation and apoptosis of human nasopharyngeal carcinoma cell line CNE-2Z.

BACKGROUND AND OBJECTIVE: Abnormal activation of Janus kinas/signal transducer and activator of transcription 3 (JAK-STAT3) signaling pathway is closely related to malignant transformation of cells. This study was to investigate the effects of a JAK inhibitor, AG490, on the proliferation, apoptosis, and expressions of apoptosis-related survivin and Mcl-1 genes, thus to explore the role of JAK-STAT3 signaling pathway in the regulation of cell apoptosis in nasopharyngeal carcinoma (NPC) cell line CNE-2Z. METHODS: CNE-2Z cells were treated with different doses of AG490. The cell proliferation was measured using MTT array. Cell apoptosis was assessed by flow cytometry (FCM) and Hoechst33342 fluorescence staining. The mRNA levels of STAT3, survivin and Mcl-1 were detected by reverse transcription-polymerase chain reaction (RT-PCR). The protein contents of STAT3, phosphoralated STAT3 (p-STAT3), survivin and Mcl-1 were measured by western blot. RESULTS: The inhibition rates of CNE-2Z cell proliferation by 100 micromol/L AG490 were 37.95% and 52.99% at 24 and 48 h after treatment. After incubation with 50 micromol/L and 100 micromol/L AG490 for 24 h, the apoptotic rates of CNE-2Z cells were increased from 1.37% to 9.30% and 9.00%, respectively (p < 0.01); typical changes in apoptotic morphology were observed under fluorescence microscopy; moreover, activation of STAT3 was inhibited, mRNA and protein levels of Mcl-1 and survivin were down-regulated. CONCLUSION: Blocking of JAK-STAT3 signaling pathway in CNE-2Z cells could remarkably inhibit cell proliferation and inactivate STAT3, as well as promote cell apoptosis by down-regulating Mcl-1 and survivin.

[Effects of Epstein-Barr virus latent membrane protein 1 on metastasis of human nasopharyngeal carcinoma cell lines].

BACKGROUND & OBJECTIVE: Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) plays an important role in the metastasis of nasopharyngeal carcinoma (NPC). This study was to investigate the effects of EBV LMP1 on the metastasis of NPC cell lines, and explore potential mechanism. METHODS: The expression of LMP1, E-cadherin and intercellular adhesion molecule-1 (ICAM-1) in human NPC cell lines CNE1 (well differentiated) and CNE1-GL (CNE1 cells transfected with LMP1) were detected by SP immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The cell-cell adhesion assay, the cell-matrix adhesion assay, the wound-induced migration assay and the migration assay were used to investigate the effects of LMP1 on adhesive and metastatic abilities of NPC cells. RESULTS: The positive rates of LMP1 and ICAM-1 were significantly lower in CNE1 cells than in CNE1-GL cells [0% vs. (96.60+/-3.03)%, P<0.01; (5.27+/-1.45)% vs. (93.33+/-4.23)%, P<0.01]; the positive rate of E-cadherin was significantly higher in CNE1 cells than in CNE1-GL cells [(37.47+/-1.50)% vs. (19.53+/-1.92)%, P<0.01]. The expression of E-cadherin was significantly inhibited (P<0.01), while the expression of ICAM-1 was significantly increased (P<0.01) in CNE1-GL cells as compared with those in CNE1 cells. The cell-cell adhesive ability of CNE1-GL cells was lower than that of CNE1 cells (P<0.05). The cell-matrix adhesive ability of CNE1-GL cells was significantly higher than that of CNE1 cells (0.60+/-0.03 vs. 0.46+/-0.01, P<0.01). The number of migrated CNE1-GL cells was higher than that of migrated CNE1 cells (119.3+/-6.0 vs. 46.3+/-7.0, P<0.05). CONCLUSION: By inhibiting E-cadherin expression and enhancing ICAM-1 expression, LMP1 may reduce the cell-cell adhesive ability and improve the cell-matrix adhesive ability and migratory ability of NPC cells, which may play roles in the invasion and metastasis of NPC.

Octylphenol stimulates resistin gene expression in 3T3-L1 adipocytes via the estrogen receptor and extracellular signal-regulated kinase pathways.

Resistin is known as an adipocyte-specific secretory hormone that can cause insulin resistance and decrease adipocyte differentiation. It can be regulated by sexual hormones. Whether environmental estrogens regulate the production of resistin is still not clear. Using 3T3-L1 adipocytes, we found that octylphenol upregulated resistin mRNA expression in dose- and time-dependent manners. The concentration of octylphenol that increased resistin mRNA levels by 50% was approximately 100 nM within 6 h of treatment. The basal half-life of resistin mRNA induced by actinomycin D was lengthened by octylphenol treatment, suggesting that octylphenol decreases the rate of resistin mRNA degradation. In addition, octylphenol stimulated resistin protein expression and release. The basal half-life of resistin protein induced by cycloheximide was lengthened by octylphenol treatment, suggesting that octylphenol decreases the rate of resistin protein degradation. While octylphenol was shown to increase activities of the estrogen receptor (ER) and MEK1, signaling was demonstrated to be blocked by pretreatment with either ICI-182780 (an ERalpha antagonist) or U-0126 (a MEK1 inhibitor), in which both inhibitors prevented octylphenol-stimulated phosphorylation of ERK. These results imply that ERalpha and ERK are necessary for the octylphenol stimulation of resistin mRNA expression. Moreover, U-0126 antagonized the octylphenol-increased resistin protein expression and release. These data suggest that the way octylphenol signaling increases resistin protein levels is similar to that by which it increases resistin mRNA levels; it is likely mediated through an ERK-dependent pathway. In vivo, octylphenol increased adipose resistin mRNA expression and serum resistin and glucose levels, supporting its in vitro effect.

The inhibition of growth and angiogenesis in heterotransplanted esophageal carcinoma via intratumoral injection of arsenic trioxide.

To investigate the antitumor action of arsenic trioxide (As2O3) by intratumoral injection into solid tumors, tumor growth inhibition (TGI) and angiogenesis of heterotransplanted esophageal carcinoma in mice was carried out. The cultured human esophageal carcinoma cells were inoculated into both laterals of the abdominal wall of severe combined immunodeficient (SCID) mice. When both lateral tumors had grown to about 10x8x5 mm(3), the right tumors were treated with an intratumoral injection of As2O3 in dosage of 1, 5 and 10 microg per day, respectively, for 10 days sequentially. Left tumors were treated with PBS (phosphate buffer solution) as control. The weight of transplanted tumor masses were measured and counted for TGI. The tissue of tumor, liver, kidney, heart, lung and brain was examined histopathologically and tumor tissues were examined by light- or electron-microscope. Ki-67 and CD34 were assessed by immunohistochemistry and positive nuclei of Ki-67 and microvessel density (MVD) labeled by CD34 were measured. The results revealed that on the 20th day after the first injection, As2O3-treated tumors were suppressed markedly as compared with the contrarily situated tumor, accompanied by a marked apoptosis and necrosis in tumor cells. The tissue of liver, kidney, heart, lung and brain was unaffected by As2O3. MVD in tumor tissue was decreased in the right side tumor with the significant difference in the 5 micro g and 10 micro g group (p<0.01). TGI was 5.80 (p>0.05), 58.66 (p<0.01) and 73.97% (p<0.01) in the 1, 5 and 10 micro g groups respectively, but 2.21% (p>0.05) in the control group. Conclusively, a repeated administration of As2O3 (5 and 10 microg x 10) induced an increase of tumor growth inhibition and decrease of angiogenesis in the solid tumor in tumor progressive periods. These results suggest that intra-tumoral injection of As2O3 may be investigated as a modality to treat some solid tumors.