Applying FAIR4RS principles to develop an integrated modeling environment for the magnetic confinement fusion.

Over the decades, the integrated modeling (IM) environment for magnetically confined fusion has evolved from a single, isolated, proprietary numerical computing software to an open, flexible platform emphasizing sharing, communication, and workflow. This development direction is consistent with the FAIR4RS principles put forward by the scientific community in recent years. In this article, we describe how the FAIR4RS principles were put into practice during the development of the IM management tool FyDev for the Experimental Advanced Superconducting Tokamak (EAST). FyDev integrates the process of building, deploying, and invoking research software, automating the entire process. FyDev can also assign a unique ID for each software, convert the software ID to a Python module, and encapsulate a package management tool to enhance the software building process, ensuring consistency throughout the entire phase of the research software find, access, use, and invocation in a uniform contextual environment.

Realization of thousand-second improved confinement plasma with Super I-mode in Tokamak EAST.

Mastering nuclear fusion, which is an abundant, safe, and environmentally competitive energy, is a great challenge for humanity. Tokamak represents one of the most promising paths toward controlled fusion. Obtaining a high-performance, steady-state, and long-pulse plasma regime remains a critical issue. Recently, a big breakthrough in steady-state operation was made on the Experimental Advanced Superconducting Tokamak (EAST). A steady-state plasma with a world-record pulse length of 1056 s was obtained, where the density and the divertor peak heat flux were well controlled, with no core impurity accumulation, and a new high-confinement and self-organizing regime (Super I-mode = I-mode + e-ITB) was discovered and demonstrated. These achievements contribute to the integration of fusion plasma technology and physics, which is essential to operate next-step devices.

A Case of Chromoblastomycosis Caused by Fonsecaea pedrosoi Successfully Treated by Oral Itraconazole Together with Terbinafine.

Patients with chromoblastomycosis (CBM) usually have a history of local skin damage related to outdoor activities, mainly manifested as chronic refractory proliferative pathologic changes. We report a case of a 56-year-old man with CBM, identified as Fonsecaea pedrosoi infection by fungal culture and gene sequencing. This patient was successfully treated with a regimen of oral itraconazole (ITZ) and terbinafine lasting 7 months. Through in vitro drug sensitivity tests, minimum inhibitory concentrations of amphotericin, ITZ, and terbinafine were 1 µg/ml, 0.25 µg/ml, and 1 µg/ml, respectively. In this case, terbinafine was found to be more effective than ITZ.

[Clinical efficacy of biofeedback and electrical stimulation combined with prostate massage in the treatment of chronic prostatitis / chronic pelvic pain syndrome].

OBJECTIVE: To investigate the effect of biofeedback and electrical stimulation combined with prostate massage on chronic prostatitis /chronic pelvic pain syndrome (CP/CPPS). METHODS: A total of 76 cases of diagnosed CP/CPPS were randomly divided into groups A (n = 20), treated by prostatic massage twice a week, B (n = 20), treated by biofeedback and electrical stimulation 5 times a week, and C (n = 20) treated by biofeedback and electrical stimulation 5 times a week combined with prostatic massage twice a week, all for 14 days. Another 16 cases were included in group D as controls left untreated. NIH-CPSI scores were obtained before and at 30 days after treatment and compared among different groups of the patients. RESULTS: Compared with the baseline, the patients in groups A, B and C showed significant decreases after treatment in the NIH-CPSI scores for pain (ï¼»13.55 ± 2.37ï¼½ vs ï¼»10.85 ± 2.28ï¼½, ï¼»13.40 ± 2.28ï¼½ vs ï¼»10.60 ± 2.23ï¼½, and ï¼»13.70 ± 3.42ï¼½ vs ï¼»8.65 ± 1.69ï¼½), urinary symptoms (ï¼»5.50 ± 1.43ï¼½ vs ï¼»3.65 ± 1.27ï¼½, ï¼»5.65 ± 1.31ï¼½ vs ï¼»3.95 ± 1.28ï¼½, and ï¼»5.40 ± 1.35ï¼½ vs ï¼»2.95 ± 1.28ï¼½), quality of life (ï¼»8.70 ± 1.81ï¼½ vs ï¼»6.90 ± 1.71ï¼½, ï¼»8.90 ± 1.12ï¼½ vs ï¼»5.80 ± 1.85ï¼½, and ï¼»8.95 ± 1.47ï¼½ vs ï¼»4.35 ± 1.53ï¼½) and the total NIH-CPSI scores (ï¼»27.75 ± 2.65ï¼½ vs ï¼»21.40 ± 3.03ï¼½, ï¼»27.95 ± 3.24ï¼½ vs ï¼»20.35 ± 3.95ï¼½, and ï¼»28.05 ± 3.78ï¼½ vs ï¼»15.95 ± 2.41ï¼½) (P < 0.05). Even more remarkable reduction was observed in the total NIH-CPSI scores in group C than in A and B (P < 0.05), but with no statistically significant difference between groups A and B (P > 0.05) or in the control group before and after the treatment (P > 0.05). CONCLUSIONS: Biofeedback and electrical stimulation combined with prostate massage has a synergistic effect on CP/CPPS by alleviating pain and urinary symptoms and improving the quality of life.

[Transurethral holmium laser enucleation of the prostate combined with Jisheng Shenqi Decoction for benign prostatic hyperplasia].

OBJECTIVE: To assess the clinical effects of transurethral holmium laser enucleation of the prostate (HoLEP) combined with Jisheng Shenqi Decoction (HoLEP + JSSD) on BPH. METHODS: This study included 110 BPH patients treated in our hospital from August 2017 to April 2018, who were randomly assigned to receive HoLEP (n = 55) or HoLEP + JSSD (n = 55). We compared the pre- and post-operative IPSS, quality of life (QOL) score, prostate volume, postvoid residual urine volume (PVR), maximum urinary flow rate (Qmax), average urinary flow rate (Qavg) and levels of serum T, E2 and T/E2 as well as postoperative complications between the two groups of patients. RESULTS: After treatment, both IPSS and QOL score were significantly lower in the HoLEP + JSSD than in the HoLEP group (P < 0.05), and so were the prostate volume and PVR (P < 0.05). The Qmax, Qavg and serum T level were significantly higher (P < 0.05) while T/E2 markedly lower in the former than in the latter group (P < 0.05). There were no statistically significant differences between the HoLEP + JSSD and HoLEP groups in the E2 level (P > 0.05) or the total incidence rate of complications postoperatively (21.82% vs 29.09%, P > 0.05). CONCLUSIONS: HoLEP + JSSD can significantly alleviate the lower urinary tract symptoms as well as improve the QOL and bladder and urinary tract functions of BPH patients.

[Clinical observation on treatment of type 2 cardiac and kidney syndrome by combination of traditional Chinese and Western medicines].

Clinical observation on treatment of type 2 cardiac and kidney syndrome by combination of traditional Chinese and Western medicine. The patients were divided into two groups： the simple Western medicine treatment group (control group) and the traditional Chinese medicine and Western medicine treatment group (treatment group). The patients in the two groups were treated with conventional western medicine.The treatment group was given based on Buxin Yishen decoction, a total of three courses of treatment to observe the two groups of patients before and after treatment of total efficacy, cardiac function indicators, changes in renal function indicators. The total efficacy of the treatment group and the control group were 91.80% and 72.41%, respectively. There were significant differences between the two groups (P<0.01). The cardiac function indexes and renal function indexes of the treatment group and the control group before and after treatment (P<0.01). Compared with the two groups, the left ventricular function, Hematuria natriuretic peptide, serum creatinine, urea nitrogen, cystatin-C were improved, and the treatment group (P<0.05~0.01). The results showed that the combination of traditional Chinese and Western medicine treatment can improve the clinical efficacy of type 2 heart and kidney syndrome, significantly improve heart and kidney function, better than conventional Western medicine treatment, and has good safety.

Contribution of HOGG1 Ser³²6Cys polymorphism to the development of prostate cancer in smokers: meta-analysis of 2779 cases and 3484 controls.

The HOGG1 gene catalyzes the excision of modified bases and removal of DNA damage adducts. It may play an important role in the prevention of carcinogenesis. Ser³²6Cys polymorphism localizes in exon 7 of the hOGG1 gene. It takes the form of an amino acid substitution, from serine to cysteine, in codon 326. Several epidemiological association studies have been conducted on this polymorphism and its relationship with the risk of prostate cancer. However, results have been conflicting. To resolve this conflict, we conducted a meta-analysis on the association between this polymorphism and prostate cancer, taking into account race, country, sources of controls, and smoking status. A total of nine studies covering 2779 cases and 3484 controls were included in the current meta-analysis. Although no significant association was found between hOGG1 Ser³²6Cys polymorphism and prostate cancer susceptibility in the pooled analysis, individuals with Ser/Cys+Cys/Cys genotypes were found to have greater risk of prostate cancer if they were also smokers (OR = 2.66, 95% CI = 1.58-4.47) rather than non-smokers (OR = 2.18, 95% CI = 1.13-4.19), compared with those with Ser/Ser genotype. In conclusion, our meta-analysis demonstrates that hOGG1 Ser³²6Cys polymorphism is a risk factor for prostate cancer in smokers. Further studies are needed to confirm this relationship.

[The study of anti-tumor activities of DC vaccine loaded with multi-epotipes of survivin].

AIM: To observe the anti-tumor activity of dendritic cell (DC)vaccine loaded with multi-epitopes of survivin. METHODS: The recombinant plasmid pPIRESneo3.0-survivin (4)/Th which include four survivin HLA-A2-restricted CD8(+); CTL epitopes and a CD4(+);Th epitope, pPIRESneo3.0-survivin (4) which include four survivin CD8(+); CTL epitopes, were transfected into human dendritic cells respectively. There were five groups, which included survivin(4)/Th group, survivin(4)group, empty plasmid group, untransfected group and T lymphocytes group The expression of CD83 and CD86 on the surface of DCs, the expression of CD4 and CD8a on the surface of T lymphocytes, the apoptotic rates of MCF-7 cells after treated by DC vaccine were measured by flow cytometry; IFN-γ levels of all groups were detected by ELISA and the growth inhibition of MCF-7 cells after being treated with DC vaccine was tested by MTT colorimetry. RESULTS: The results of flow cytometry revealed that high levels CD83 and CD86 were expressed on the surface of DCs; high levels CD4 and CD8a were expressed on the surface of T lymphocytes; the IFN-γ levels in survivin(4)/Th group [(66.50±3.34)ng/L]were significantly higher than that in survivin(4)group[(46.10±1.35)ng/L], empty plasmid group[(25.17±0.32)ng/L], untransfected group [(25.47±0.95)ng/L] or T lymphocytes group[(23.73±0.50)ng/L](P<0.05). The inhibition rate of MCF-7 cells in survivin(4)/Th group was significantly higher than that in survivin(4)group, empty plasmid group, untransfected group or T lymphocytes group(P<0.05). The apoptotic rate of MCF-7 cells in survivin(4)/Th group was (10.63±0.29)% after treated by DC vaccine, which was significantly higher than that in in survivin(4)group, empty plasmid group, untransfected group or T lymphocytes group(P<0.05). CONCLUSION: The DCs vaccine loaded with multi- CD8(+); CTL epitopes of survivin has strong anti-tumor effects. CD4(+); Th cells can promote the anti-tumor activity of CD8(+);CTL.

[Construction of the eukaryotic expression vector encoding multi-epitope fusion protein of human survivin and its expression in dendritic cells].

AIM: To construct a eukaryotic expression vector encoding the multi-epitope fusion protein of human survivin, and express it in human dendritic cells. METHODS: Recombinant cDNA sequence encoding four HLA-A2-restricted CD8+ CTL epitopes and a CD4+ Th epitope was synthesized and cloned into pBluescript II SK (+) vector. After confirmed by sequencing, the cDNA fragment was inserted to eukaryotic expression vector pIRESneo3.0 to generate the recombinant plasmid pPIRESneo3.0-survivin (4)/Th. The pPIRESneo3.0-survivin (4)/Th was then transfected into human dendritic cells and the transfectants were selected for stable expression. RESULTS: The eukaryotic expression vector encoding the multi-epitope fusion protein of survivin was constructed, and successfully transfected into human dendritic cells. CONCLUSION: The eukaryotic expression vector encoding the multi-epitope fusion protein of survivin has been constructed successfully, and stably expressed in human dendritic cells, which provides clues for further research on multi-epitope cancer vaccine.

Comparative evaluation of two laparoscopic procedures for treating common bile duct stones.

Cholesystolithiasis is often associated with common bile duct stones (CBDS). In order to assess the choice of surgery in terms of effectiveness and complications in the treatment of CBDS, we have compared three surgical procedures, viz., laparoscopic choledocholithotomy T-tube drainage (LCH-TD), laparoscopic cholecystectomy with endoscopic sphincterotomy (LC-EST), and the traditional open choledocholithotomy with T-tube drainage (OCHTD). This study is a retrospective comparative analysis of LCH-TD (77 patients), LC-EST (43 patients), and OCHTD (60 patients) for CBDS. The success of the surgical procedures was assessed in terms of recovery duration, hospitalization, and post-operative complications. Both the micro-invasive procedures, LCH-TD and LC-EST, with a success rate of 92.5%, are found to be superior to the traditional OCHTD. Between the two micro-invasive procedures, patients in LCH-TD group had shorter operation time and hospital stay, and fewer post-operative complications. Although the size of the stones is comparable between these two groups, the CBD diameter was significantly larger in patients who underwent LCH-TD. In comparison to OCHTD, both LCH-TD and LC-EST are micro-invasive, safe, and suitable for routine use in patients with CBDS. Moreover, when the CBD diameter is wider than 1 cm, LCH-TD is strongly advocated.

[Modulation of histone acetylation and induction of apoptosis in SMMC-7721 cells by phenylhexyl isothiocyanate].

OBJECTIVE: To investigate the effect of phenylhexyl isothiocyanate (PHI) on histone acetylation and apoptosis in hepatocellular carcinoma cell line (SMMC-7721) in vitro. METHODS: The viability of SMMC-7721 cells was determined by trypan blue exclusion. Apoptotic cells were assessed by TUNEL assay. The proteins of Bcl-2, Procaspase-9, Procaspase-8, Procaspase-3, caspase-9, caspase-3, histone acetylated H3 and H4 were detected by Western blot. RESULTS: Compared with the vehicle control, PHI at 5, 10, 20, 40 and 80 µmol/L reduced the cell viability of SMMC-7721 cells in a concentration-dependent manner. PHI induced apoptosis in SMMC-7721 cells. An increased amount of apoptotic cells was detected after 7 hours exposure to PHI at 10, 20, and 40 µmol/L, 6.9% ± 2.4%, 17.5% ± 4.2% and 54.5% ± 5.4%, respectively, while that of the vehicle control was 4.5% ± 2.3% (P < 0.05). Along with the prolongation of time and increase of dose, the expressions of bcl-2, procaspase-9, procaspase-3 were decreased, that of caspase-9 and caspase-3 was increased. In contrast, alteration of procaspase-8 was not significant at those concentrations. PHI accumulated acetylated histone H3 and H4. After 3 hours exposure to PHI at 10, 20 and 40 µmol/L, the level of histone acetylated H3 was 1.87-, 2.43-, 3.67-fold increased and histone acetylated H4 was 1.29-, 1.45-, and 2.25-fold increased, compared with that of the vehicle control. The protein of histone acetylated H3 and H4 was significantly accumulated after 7 hours exposure. CONCLUSION: PHI is a new histone deacetylation inhibitor. It may induce accumulation of histone acetylation H3 and H4, inhibit cell growth and induce apoptosis in SMMC-7721 cells via the mitochondrial pathway.

Effects of selenite and genistein on G2/M cell cycle arrest and apoptosis in human prostate cancer cells.

Combination of chemopreventive agents with distinct molecular mechanisms is considered to offer a potential for enhancing cancer prevention efficacy while minimizing toxicity. Here we report two chemopreventive agents, selenite and genistein, that have synergistic effects on apoptosis, cell cycle arrest, and associated signaling pathways in p53-expressing LNCaP and p53-null PC3 prostate cancer cells. We show that selenite induced apoptosis only, whereas genistein induced both apoptosis and G2/M cell cycle arrest. Combination of these two agents exhibited enhanced effects, which were slightly greater in LNCaP than PC3 cells. Selenite or genistein alone upregulated protein levels of p53 in LNCaP cells only and p21(waf1) and Bax in both cell lines. Additionally, genistein inhibited AKT phosphorylation. Downregulation of AKT by siRNA caused apoptosis and G2/M cell cycle arrest and masked the effects of genistein. Treatment with insulin-like growth factor I (IGF-I) elevated levels of total and phosphorylated AKT and suppressed the effects of genistein. Neither downregulation of AKT nor IGF-I treatment altered the cellular effects of selenite. Our study demonstrates that selenium and genistein act via different molecular mechanisms and exhibit enhanced anticancer effects, suggesting that a combination of selenium and genistein may offer better efficacy and reduction of toxicity in prostate cancer prevention.

Peptidergic not monoaminergic fibers profusely innervate the young adult human testis.

Numerous studies have reported that intratesticular nerves exert important regulatory effects on the functions of the male gonad; however, as yet little is known about their distribution in the young adult human testis. The purpose of this study was to explore whether peptidergic and adrenergic nerves occur in the male gonad of this age, and, if present, to depict their distribution further. Thirty testes were collected from 15 reproductively healthy donors aged 21-32 years. Antibodies against protein gene product 9.5 (PGP 9.5), neuropeptide Y (NPY), C-terminal flanking peptide of NPY (CPON) and vasoactive intestinal peptide (VIP) were employed for immunohistochemical detection of intratesticular peptidergic nerves, and those against dopamine-beta-hydroxylase (DBH) and 5-hydroxytryptamine (5-HT) for monoaminergic ones. The testicular parenchyma exhibited a rich innervation by PGP 9.5-positive fibers, mainly associated with Leydig cell nests, blood vessels, and seminiferous tubules. Numerous NPY- and CPON-immunoreactive (IR) nerves also appeared in the gonads, but the vast majority were confined to blood vessels. A small number of VIP-IR fibers were detected in some arterioles. By contrast, however, no fibers displaying DBH or 5-HT immunoreactivity were observed within the testis. Additionally, expression of PGP-9.5, NPY, CPON, VIP, DBH and 5-HT was found in Leydig cells, PGP 9.5 in spermatogonia, and NPY and CPON in peritubular myoid cells. Our results suggest that the young adult human testis is devoid of monoaminergic nerves but profusely innervated by peptidergic fibers, which may serve as major neuronal regulators for testicular functions at this age.

Sodium selenite induces apoptosis by generation of superoxide via the mitochondrial-dependent pathway in human prostate cancer cells.

PURPOSE: Studies have demonstrated that selenium supplementation reduces the incidence of cancer, particularly prostate cancer. Evidence from experimental studies suggests that apoptosis is a key event in cancer chemoprevention by selenium and reactive oxygen species play a role in induction of apoptosis by selenium compounds. The current study was designed to investigate the role of superoxide and mitochondria in selenite-induced apoptosis in human prostate cancer cells. METHODS: LNCaP cells were transduced with adenoviral constructs to overexpress four primary antioxidant enzymes: manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), or glutathione peroxidase 1 (GPx1). Cell viability, apoptosis, and superoxide production induced by sodium selenite were analyzed by the MTT assay, chemiluminescence, flow cytometry, western blot analysis, and Hoechst 33342 staining following overexpression of these antioxidant enzymes. RESULTS: Our study shows the following results: (1) selenite induced cancer cell death and apoptosis by producing superoxide radicals; (2) selenite-induced superoxide production, cell death, and apoptosis were inhibited by overexpression of MnSOD, but not by CuZnSOD, CAT, or GPx1; and (3) selenite treatment resulted in a decrease in mitochondrial membrane potential, release of cytochrome c into the cytosol, and activation of caspases 9 and 3, events that were suppressed by overexpression of MnSOD. CONCLUSIONS: This study demonstrates that selenite induces cell death and apoptosis by production of superoxide in mitochondria and activation of the mitochondrial apoptotic pathway and MnSOD plays an important role in protection against prooxidant effects of superoxide from selenite. The data suggest that superoxide production in mitochondria is, at least in part, a key event in selenium-induced apoptosis in prostate cancer cells.

Selenite reactivates silenced genes by modifying DNA methylation and histones in prostate cancer cells.

DNA hypermethylation is a common epigenetic alteration in human prostate cancer and is considered to contribute to development of this disease. Accumulating data suggest that dietary factors may alter cancer risk by modifications of epigenetic processes in the cell. The present study was designed to investigate whether selenium (Se) would alter epigenetic events to regulate methylation-silenced genes in human prostate cancer cells. DNA methylation, histone modifications and gene expression were studied in LNCaP cells after selenite treatment using polymerase chain reaction, western blot analysis, chromatin immunoprecipitation assay and enzymatic activity assay. Our study shows that selenite treatment caused partial promoter DNA demethylation and reexpression of the pi-class glutathione-S-transferase (GSTP1) in LNCaP cells in a dose- and time-dependent manner. Selenite treatment decreased messenger RNA levels of DNA methyltransferases (DNMTs) 1 and 3A and protein levels of DNMT1. Selenite also decreased histone deacetylase activity and increased levels of acetylated lysine 9 on histone H3 (H3-Lys 9), but decreased levels of methylated H3-Lys 9. Selenite treatment reduced levels of DNMT1 and methylated H3-Lys 9 associated with the GSTP1 promoter, but increased levels of acetylated H3-Lys 9 associated with this promoter. Additionally, selenite treatment decreased general DNA methylation and caused partial promoter demethylation and reexpression of the tumor suppressor adenomatous polyposis coli and cellular stress response 1, a gene involving tumor growth and metastasis. Our study demonstrates that Se can epigenetically modulate DNA and histones to activate methylation-silenced genes. These epigenetic modifications may contribute to cancer prevention by Se.

Second-harmonic generation of electron-bernstein waves in an inhomogeneous plasma.

In the injection of electron-Bernstein waves (EBW) into a plasma, proposed for plasma heating and current drive in over-dense plasma, conversion of the fundamental to its second harmonic is predicted analytically and observed in computations. The mechanism is traced to the existence of locations where one can have both wave number and frequency matching between the fundamental and its harmonic. Further, at such locations, the second harmonic commonly has minimal group velocity, and this allows the amplitude of the second harmonic to build to values exceeding that of the fundamental at power levels less than anticipated in experiments. The second-harmonic power can then be deposited at half-harmonic resonances of the original wave, often far from the desired location of energy deposition. Estimates for the power at which this is significant are given.

siRNA mediated the type 1 insulin-like growth factor receptor and epidermal growth factor receptor silencing induces chemosensitization of liver cancer cells.

PURPOSE: This study was to investigate if downregulation of IGF1R and EGFR by RNA interference (RNAi) would sensitize human liver cancer cells (HEPG2, Huh7 ) to adriamycin. METHODS: HEPG2, Huh7 cell lines were transfected IGF1R siRNAs and EGFR siRNAs and IGF1R or EGFR mRNA level was determined by RT-PCR and Western-blot analysis. We investigated the effects of the adriamycin-induced apoptosis of these cells by TUNEL assay. Also we analyze caspase3, 8 and the phosphorylation levels of Akt and Erk by Western-blot. The p53 effect of adriamycin-induced cell death by inhibitors of EGFR/IGF1R is investigated by cell growth curves. RESULTS: Transfection of an IGF1R and EGFR siRNAs resulted in substantial loss of IGF1R and EGFR mRNA of HEPG2, Huh7 cells relative to the control case. EGFR siRNA and IGF1R siRNA treatments increased the adriamycin-induced apoptosis of these cells. IGF1R siRNA and EGFR siRNA enhance a caspase-dependent cell death program. The phosphorylation levels of Akt and Erk were reduced by the combination of the two agents. The facilitation of adriamycin-induced cell death by inhibitors of EGFR/IGF1R is p53-independent. CONCLUSIONS: The results indicate that the siRNA for IGF1R has a great potential for cancer therapy when combined with either a chemotherapeutic agent or siRNAs that targets EGFR.

[Inhibitory effect of IGF1R siRNA on the growth of human liver cancer SMMC7721 cell xenograft in nude mice].

BACKGROUND & OBJECTIVE: Using small interfering RNA (siRNA) to inhibit mammal gene expression becomes an effective technique in studying gene function. This study was to investigate the effect of insulin-like growth factor 1 receptor (IGF1R) siRNA on the growth of human liver cancer SMMC7721 cell xenograft in nude mice. METHODS: siRNA targeting IGF1R was designed, and plasmid SMMC7721-IGF1R-siRNA was constructed and transfected into SMMC7721 cells (SMMC7721-IGF1R-siRNA cells); the cells transfected with SMMC7721-IGF1R-mutation (SMMC7721-IGF1R-mutation cells) were used as negative control, and untransfected cells as empty control. Stable cell clones were screened by G418, and transplanted into nude mice to establish cancer xenograft. Tumor growth was monitored. Tumor morphology was observed with HE staining. The expression of IGF1R protein in tumor tissues was detected by Western blot. Microvessel density (MVD) in tumor tissues was detected by SP immunohistochemistry. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. RESULTS: The tumor volume was significantly smaller in SMMC7721-IGF1R-siRNA group than in SMMC7721-IGF1R-mutation group and SMMC7721 group (P < 0.05). Necrosis and cell apoptosis were found in SMMC7721-IGF1R-siRNA group. The expression of IGF1R protein was significantly lower in SMMC7721-IGF1R-siRNA group than in SMMC7721-IGF1R-mutation group and SMMC7721 group (P < 0.05). MVD was significantly lower in SMMC7721-IGF1R-siRNA group than in SMMC7721-IGF1R-mutation group and SMMC7721 group (11.3+/-4.4 vs. 36.7+/-7.6 and 28.4+/-6.5, P < 0.05). The apoptosis rate of tumor cells was significantly higher in SMMC7721-IGF1R-siRNA group than in SMMC7721-IGF1R-mutation group and SMMC7721 group [(50.2+/-6.4)% vs. (5.4+/-1.0)% or (6.0+/-2.1)%, P < 0.05]. CONCLUSION: IGF1R siRNA can inhibit the growth of SMMC7721 cell xenograft in nude mice.

siRNA-mediated type 1 insulin-like growth factor receptor silencing induces chemosensitization of a human liver cancer cell line with mutant P53.

Overexpression of type 1 insulin-like growth factor receptor (IGF1R) contributes to the progression and metastasis of liver cancer, implying that IGF1R gene is a suitable target of RNA interference (RNAi) for liver cancer therapy. To investigate the possible regulation of IGF1R by P53, we examined the level of IGF1R expression in liver cancer cell lines in response to adriamycin. Levels of IGF1R mRNA and protein in cell lines with wild-type P53 decreased dramatically after P53 induction, but no such reduction of IGF1R was observed in cell lines with mutated P53. Inhibition of wild-type P53 in HEPG2 cells by small interfering RNA (siRNA) significantly upregulated the expression of IGF1R. IGF1R inhibition by siRNA in Huh7 cells with mutated P53 significantly depressed cell proliferation. To investigate the sensitivity of cancer cells to adriamycin after inhibition of IGF1R, we depressed IGF1R expression using siRNA, and then added adriamycin at an IC50 dose. After a further 48 h incubation with adriamycin, proliferation was significantly depressed in the cells treated with siRNA targeting IGF1R, in comparison with siRNA targeting scramble. Furthermore, both TUNEL and pro-caspase-3 expression assay showed a significant increase in apoptosis after combined treatment with adriamycin and siRNA targeting IGF1R. Our results demonstrate that IGF1R is downregulated by P53, and that siRNA targeting of IGF1R increases liver cancer cells sensitivity to adriamycin and promotes apoptosis. siRNA targeting of IGF1R could be potentially useful for increasing sensitivity to anti-cancer drugs, especially in drug-resistant cells with mutated P53.

Wave excitation in inhomogeneous dielectric media.

The equation describing the propagation of a mode driven by external currents in an inhomogeneous dielectric is derived from the principle of the conservation of wave energy density and wave momentum density. The wave amplitude in steady state is obtained in terms of a simple spatial integration of the driving current. The contribution from the spatial derivative of the dielectric response is found to be important. The analytical predictions are verified through comparison with deltaf particle-in-cell computations of electron Bernstein wave propagation, thus showing applicability to kinetic systems.