Ameliorative Effects of Neurolytic Celiac Plexus Block on Stress and Inflammation in Rats with Partial Hepatectomy

Purpose: To investigate effects of neurolytic celiac plexus block (NCPB) on stress and inflammation in rats with partial hepatectomy (PH).Methods: A model of PH rat was established, and serum C-reactive protein (CRP); corticosterone (GC); adrenocorticotropin (ACTH); noradrenaline (NA); adrenalin (AD); aspartate transaminase (AST); alanine transaminase (ALT); as well as tumor necrosis factor-α (TNF-α); interleukin (IL)-1β and IL-6; high mobility group box1 (HMGB1); and nitric oxide (NO) concentrations in serum assessed after PH. Additionally, Western blotting was performed to determine the effect of NCPB on expressions of glucocorticoid receptors (GR), inhibitor of nuclear factor kappa B (IκB), p65, c-Jun and inducible nitric oxide synthase (iNOS) of PH rats, as well as assay effects of NCPB on nuclear translocation of GR, c- Jun and p65. DNA binding activities of nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1) were also determined.Results: NCPB reduced AST and ALT (P < 0.05), decreased secretion of inflammatory cytokines and NO (P < 0.05), as well as decreased CRP, GC, ACTH, NA and AD after PH (p < 0.05). NCPB increased expressions of GR and IκB, but expressions of p65, c-Jun, and iNOS (p < 0.05). Additionally, NCPB increased nuclear translocation of GR (p < 0.01), but decreased nuclear translocation of p65 and c-Jun after PH (p < 0.05). Additionally, DNA binding activity of NF-κB and AP-1 was decreased by NCPB (p < 0.05).Conclusion: The results indicate that NCPB treatment can significantly inhibit stress and inflammation in PH rats.Keywords: Neurolytic celiac plexus block, Cytokine, Nuclear translocation, Partial hepatectomy, Stress, Inflammatio

Ion-implantation induced nano distortion layer and its influence on nonlinear optical properties of ZnO single crystals

Author name used in this publication: G. Y. Gao2011-2012 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

The use of nanocrystal quantum dot as fluorophore reporters in molecular beacon-based assays

textversion:publishe

The Prognostic Value of 14-3-3 Isoforms in Vulvar Squamous Cell Carcinoma Cases: 14-3-3β and ε Are Independent Prognostic Factors for These Tumors

BACKGROUND: The 14-3-3 family is comprised of highly conserved proteins that are functionally important in the maintenance of homeostasis. Their involvement with the cell cycle, their association with proto-oncogenes and oncogenes, and their abnormal expression in various tumors has linked this family of proteins to the etiology of human cancer. Mounting evidence now indicates that 14-3-3σ is a cancer suppressor gene but the roles of the other 14-3-3 isoforms and their interactions in tumorigenesis have not yet been elucidated. In our current study, we examined the expression of 14-3-3β, γ, ε, ζ, η and τ in a large series of vulvar squamous cell carcinomas to evaluate any clinical significance. METHODS: Tumor biopsies from 298 vulvar carcinomas were examined by immunohistochemistry for the expression of 14-3-3β, γ, ε, ζ, η and τ. Statistical analyses were employed to validate any associations between the expression of any 14-3-3 isoform and clinicopathologic variables for this disease. RESULTS: High cytoplasmic levels of 14-3-3β, γ, ζ, ε and η were observed in 79%, 58%, 50%, 86% and 54% of the vulvar carcinomas analyzed, respectively, whereas a low nuclear expression of 14-3-3τ was present in 80% of these cases. The elevated cytoplasmic expression of 14-3-3β, γ, ε, ζ and η was further found to be associated with advanced disease and aggressive features of these cancers. The overexpression of cytoplasmic 14-3-3β and ε significantly correlated with a poor disease-specific survival by univariate analysis (P = 0.007 and P = 0.04, respectively). The independent prognostic significance of these factors was confirmed by multivariate analysis (P = 0.007 and P = 0.009, respectively). CONCLUSIONS: We reveal for the first time that the 14-3-3β, γ, ε, ζ, η and τ isoforms may be involved in the progression of vulvar carcinomas. Furthermore, our analyses show that high cytoplasmic levels of 14-3-3β and ε independently correlate with poor disease-specific survival

Phyllanthus spp. Induces Selective Growth Inhibition of PC-3 and MeWo Human Cancer Cells through Modulation of Cell Cycle and Induction of Apoptosis

BACKGROUND: Phyllanthus is a traditional medicinal plant that has been used in the treatment of many diseases including hepatitis and diabetes. The main aim of the present work was to investigate the potential cytotoxic effects of aqueous and methanolic extracts of four Phyllanthus species (P.amarus, P.niruri, P.urinaria and P.watsonii) against skin melanoma and prostate cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: Phyllanthus plant appears to possess cytotoxic properties with half-maximal inhibitory concentration (IC(50)) values of 150-300 µg/ml for aqueous extract and 50-150 µg/ml for methanolic extract that were determined using the MTS reduction assay. In comparison, the plant extracts did not show any significant cytotoxicity on normal human skin (CCD-1127Sk) and prostate (RWPE-1) cells. The extracts appeared to act by causing the formation of a clear "ladder" fragmentation of apoptotic DNA on agarose gel, displayed TUNEL-positive cells with an elevation of caspase-3 and -7 activities. The Lactate Dehydrogenase (LDH) level was lower than 15% in Phyllanthus treated-cancer cells. These indicate that Phyllanthus extracts have the ability to induce apoptosis with minimal necrotic effects. Furthermore, cell cycle analysis revealed that Phyllanthus induced a Go/G1-phase arrest on PC-3 cells and a S-phase arrest on MeWo cells and these were accompanied by accumulation of cells in the Sub-G1 (apoptosis) phase. The cytotoxic properties may be due to the presence of polyphenol compounds such as ellagitannins, gallotannins, flavonoids and phenolic acids found both in the water and methanol extract of the plants. CONCLUSIONS/SIGNIFICANCE: Phyllanthus plant exerts its growth inhibition effect in a selective manner towards cancer cells through the modulation of cell cycle and induction of apoptosis via caspases activation in melanoma and prostate cancer cells. Hence, Phyllanthus may be sourced for the development of a potent apoptosis-inducing anticancer agent

MYCT1-TV, A Novel MYCT1 Transcript, Is Regulated by c-Myc and May Participate in Laryngeal Carcinogenesis

BACKGROUND: MYCT1, a putative target of c-Myc, is a novel candidate tumor suppressor gene cloned from laryngeal squamous cell carcinoma (LSCC). Its transcriptional regulation and biological effects on LSCC have not been clarified. METHODOLOGY/PRINCIPAL FINDINGS: Using RACE assay, we cloned a 1106 bp transcript named Myc target 1 transcript variant 1 (MYCT1-TV) and confirmed its transcriptional start site was located at 140 bp upstream of the ATG start codon of MYCT1-TV. Luciferase, electrophoretic mobility shift and chromatin immunoprecipitation assays confirmed c-Myc could regulate the promoter activity of MYCT1-TV by specifically binding to the E-box elements within -886 to -655 bp region. These results were further verified by site-directed mutagenesis and RNA interference (RNAi) assays. MYCT1-TV and MYCT1 expressed lower in LSCC than those in paired adjacent normal laryngeal tissues, and overexpression of MYCT1-TV and MYCT1 could inhibit cell proliferation and invasion and promote apoptosis in LSCC cells. CONCLUSIONS/SIGNIFICANCE: Our data indicate that MYCT1-TV, a novel MYCT1 transcript, is regulated by c-Myc and down-regulation of MYCT1-TV/MYCT1 could contribute to LSCC development and function

Inhibition of Specific NF-κB Activity Contributes to the Tumor Suppressor Function of 14-3-3σ in Breast Cancer

14-3-3σ is frequently lost in human breast cancers by genetic deletion or promoter methylation. We have now investigated the involvement of 14-3-3σ in the termination of NF-κB signal in mammary cells and its putative role in cancer relapse and metastasis. Our results show that 14-3-3σ regulates nuclear export of p65-NF-κB following chronic TNFα stimulation. Restoration of 14-3-3σ in breast cancer cells reduces migration capacity and metastatic abilities in vivo. By microarray analysis, we have identified a genetic signature that responds to TNFα in a 14-3-3σ-dependent manner and significantly associates with different breast and other types of cancer. By interrogating public databases, we have found that over-expression of this signature correlates with poor relapse-free survival in breast cancer patients. Finally, screening of 96 human breast tumors showed that NF-κB activation strictly correlates with the absence of 14-3-3σ and it is significantly associated with worse prognosis in the multivariate analysis. Our findings identify a genetic signature that is important for breast cancer prognosis and for future personalized treatments based on NF-κB targeting

The role of propranolol as a radiosensitizer in gastric cancer treatment

Xinhua Liao, Prakash Chaudhary, Guanglin Qiu, Xiangming Che, Lin Fan General Surgery Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China Purpose: The National Comprehensive Cancer Network guidelines indicate that radiotherapy in gastric cancer shows limited effectiveness at reducing the growth of gastric cancer. Therefore, enhancing the sensitivity and effect of radiotherapy with propranolol, a β-adrenoceptor antagonist, could reduce tumor growth. The role of propranolol as a radiosensitizer has not been adequately studied; therefore, the purpose of the present study is to evaluate the effect of propranolol as a radiosensitizer against gastric cancer in vivo. Methods: Sixty-four male nude mice bearing tumor xenografts were randomly divided into four groups. Cell culture was performed using the human gastric adenocarcinoma cell line SGC-7901. Mice with tumor xenografts were treated with propranolol, isoproterenol, and radiation. The data for tumor weight and volume were obtained for statistical analyses. Furthermore, the expression levels of COX-2, NF-κB, VEGF, and EGFR were examined using immunohistochemical techniques and Western blotting.Results: The growth in the volume and weight of the tumor was lower in mouse models treated with propranolol and radiation therapy compared to the other groups. Decreased expression of NF-κB was also observed in treatment groups where both propranolol and radiation were used, leading to the reduction of COX-2, EGFR, and VEGF expression compared to that in the other groups.Conclusion: The present study indicated that propranolol potentiates the antitumor effects of radiotherapy in gastric cancer by inhibiting NF-κB expression and its downstream genes: VEGF, EGFR, and COX-2. Keywords: propranolol, radiosensitizer, gastric cancer, radiation therapy&nbsp