Search results for: prostate stromal cell cultures

Authors: Olivia Rachel Hwang, Yu-Hsuan Joni Shao

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Androgen Deprivation Therapy (ADT) has been a primary treatment for patients with advanced prostate cancer. However, it is associated with numerous adverse effects related to Metabolic Syndrome (MetS), including hypertension, diabetes, hyperlipidaemia, heart diseases and ischemic strokes. However, complications associated with ADT for prostate cancer in Taiwan is not well documented. The purpose of this study is to utilize the data from NHIRD (National Health Insurance Research Database) to examine the trajectory changes of MetS-related complications in men receiving ADT. The risks of developing complications after the treatment were analyzed with multivariate Cox regression model. Covariates including in the model were the complications before the diagnosis of prostate cancer, the age, and the year at cancer diagnosis. A total number of 17268 patients from 1997-2013 were included in this study. The exclusion criteria were patients with any other types of cancer or with the existing MetS-related complications. Changes in MetS-related complications were observed among two treatment groups: 1) ADT (n=9042), and 2) non-ADT (n=8226). The ADT group appeared to have an increased risk in hypertension (hazard ratio 1.08, 95% confidence interval 1.03-1.13, P = 0.001) and hyperlipidemia (hazard ratio 1.09, 95% confidence interval 1.01-1.17, P = 0.02) when compared with non-ADT group in the multivariate Cox regression analyses. In the risk of diabetes, heart diseases, and ischemic strokes, ADT group appeared to have an increased but not significant hazard ratio. In conclusion, ADT was associated with an increased risk in hypertension and hyperlipidemia in prostate cancer patients in Taiwan. The risk of hypertension and hyperlipidemia should be considered while deciding on ADT, especially those with the known history of hypertension and hyperlipidemia.

Keywords: androgen deprivation therapy, ADT, complications, metabolic syndrome, MetS, prostate cancer

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Authors: Natascha C. D'Amico, Enzo Grossi, Giovanni Valbusa, Ala Malasevschi, Gianpiero Cardone, Sergio Papa

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Purpose: To characterize, through a radiomic approach, the nature of areas classified PI-RADS (Prostate Imaging Reporting and Data System) 3/5, recognized in multiparametric prostate magnetic resonance with T2-weighted (T2w), diffusion and perfusion sequences with paramagnetic contrast. Methods and Materials: 24 cases undergoing multiparametric prostate MR and biopsy were admitted to this pilot study. Clinical outcome of the PI-RADS 3/5 was found through biopsy, finding 8 malignant tumours. The analysed images were acquired with a Philips achieva 1.5T machine with a CE- T2-weighted sequence in the axial plane. Semi-automatic tumour segmentation was carried out on MR images using 3DSlicer image analysis software. 45 shape-based, intensity-based and texture-based features were extracted and represented the input for preprocessing. An evolutionary algorithm (a TWIST system based on KNN algorithm) was used to subdivide the dataset into training and testing set and select features yielding the maximal amount of information. After this pre-processing 20 input variables were selected and different machine learning systems were used to develop a predictive model based on a training testing crossover procedure. Results: The best machine learning system (three-layers feed-forward neural network) obtained a global accuracy of 90% ( 80 % sensitivity and 100% specificity ) with a ROC of 0.82. Conclusion: Machine learning systems coupled with radiomics show a promising potential in distinguishing benign from malign tumours in PI-RADS 3/5 areas.

Keywords: machine learning, MR prostate, PI-Rads 3, radiomics

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Authors: Kuplevatsky V., Kuplevatskay, Cherkashin M., Berezina N.

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After 6 months, a violation of the differentiation of the structure of the gland due to edema in 100%. 20% retained signs of a tumor according to DWI/ADC data. By 12 months, the reduction in the size of the gland is 100%. In all cases, no diffusion restriction was observed. The study after 18 months showed no significant changes in all (100%) patients. In the study, 24 months after treatment, the size of the gland was stable in all cases (+/- up to 5%). Diffuse decrease in T2VI signals from peripheral zones, without signs of diffusion restriction in 100%. After 30 months, signs of recovery of adenomatous changes in the transient zone were revealed in 85%. After 36 and 42 months, the restoration of organ differentiation was observed in 93% of patients. In 4 patients, by the 48th month, signs of biochemical relapse were clinically noted. According to the MRI data, signs of a local relapse were revealed. After 48 months, there were signs of restoration of organ differentiation, which allowed the use of PI-RADS criteria. The study after 54 months showed no changes compared to the control. 60 months after treatment, 97% of patients showed a restoration of differentiation of the gland structure, which allows evaluating the organ according to PI-RADS criteria Conclusions: The beginning of restoration of the structure of the prostate gland began 24 months after proton radiation therapy, the PI-RADS criteria can be fully applied after 48 months of treatment. Control studies every 6 months without clinical signs of relapse are not advisable. Local control of the prostate tumor after proton radiation therapy was achieved in 95% of patients during the entire follow-up period ( 60 months).

Keywords: proton therapy, prostate cancer, MRI imaging, PI-RADS

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Authors: Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Yung Hyun Choi, Gi-Young Kim

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Camptothecin (CPT) is a quinolone alkaloid which inhibits DNA topoisomerase I that induces cytotoxicity in a variety of cancer cell lines. We previously showed that CPT effectively inhibited invasion of prostate cancer cells and also combined treatment with subtoxic doses of CPT and TNF-related apoptosis-inducing ligand (TRAIL) potentially enhanced apoptosis in a caspase-dependent manner in hepatoma cancer cells. Here, we found that treatment with CPT caused an irreversible cell cycle arrest in the G2/M phase. CPT-induced cell cycle arrest was associated with a decrease in protein levels of cell division cycle 25C (Cdc25C) and increased the level of cyclin B and p21. The CPT-induced decrease in Cdc25C was blocked in the presence of proteasome inhibitor MG132, thus reversed the cell cycle arrest. In addition to that treatment of CPT-increased phosphorylation of Cdc25C was the resulted of activation of checkpoint kinase 2 (Chk2), which was associated with phosphorylation of ataxia telangiectasia-mutated. Interestingly CPT induced G2/M phase of the cell cycle arrest is reactive oxygen species (ROS) dependent where ROS inhibitors NAC and GSH reversed the CPT-induced cell cycle arrest. These results further confirm by using transient knockdown of nuclear factor-erythroid 2-related factor 2 (Nrf2) since it regulates the production of ROS. Our data reveal that treatment of siNrf2 increased the ROS level as well as further increased the CPT induce G2/M phase cell cycle arrest. Our data also indicate CPT-enhanced cell cycle arrest through the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more decreased the Cdc25C expression and protein expression of p21 and cyclin B. These findings indicate that Chk2-mediated phosphorylation of Cdc25C plays a major role in G2/M arrest by CPT.

Keywords: camptothecin, cell cycle, checkpoint kinase 2, nuclear factor-erythroid 2-related factor 2, reactive oxygen species

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Authors: Mojtaba Mirmontazemi, Habibollah Dadgar

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Bone is the most common metastasis site in some advanced malignancies, such as prostate and breast cancer. Bone metastasis generally indicates fewer prognostic factors in these patients. Different radiological and molecular imaging modalities are used for detecting bone lesions. Molecular imaging including computed tomography, magnetic resonance imaging, planar bone scintigraphy, single-photon emission tomography, and positron emission tomography as noninvasive visualization of the biological occurrences has the potential to exact examination, characterization, risk stratification and comprehension of human being diseases. Also, it is potent to straightly visualize targets, specify clearly cellular pathways and provide precision medicine for molecular targeted therapies. These advantages contribute implement personalized treatment for each patient. Currently, NaF PET/CT has significantly replaced standard bone scintigraphy for the detection of bone metastases. On one hand, 68Ga-PSMA PET/CT has gained high attention for accurate staging of primary prostate cancer and restaging after biochemical recurrence. On the other hand, FDG PET/CT is not commonly used in osseous metastases of prostate and breast cancer as well as its usage is limited to staging patients with aggressive primary tumors or localizing the site of disease. In this article, we examine current studies about FDG, NaF, and PSMA PET/CT images in bone metastases diagnostic utility and assess response to treatment in patients with breast and prostate cancer.

Keywords: skeletal metastases, fluorodeoxyglucose, sodium fluoride, molecular imaging, precision medicine, prostate cancer (68Ga-PSMA-11)

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Authors: Youn Young Shim, Ji Hye Kim, Jae Youl Cho, Martin J. T. Reaney

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Flaxseed (Linum usitatissimum L.) is gaining popularity in the food industry as a superfood due to its health-promoting properties. The flax plant synthesizes an array of biologically active cyclic peptides or linusorbs (LOs, a.k.a. cyclolinopeptides) from three or more ribosome-derived precursors. [1–9-NαC]-linusorb B3 and [1–9-NαC]-linusorb B2, suppress immunity, induce apoptosis in human epithelial cancer cell line (Calu-3) cells, and inhibit T-cell proliferation, but the mechanism of LOs action is unknown. Using gene expression analysis in nematode cultures and human cancer cell lines, we have observed that LOs exert their activity, in part, through induction of apoptosis. Specific LOs’ properties include: 1) distribution throughout the body after flaxseed consumption; 2) induce heat shock protein (HSP) 70A production as an indicator of stress and address the issue in Caenorhabditis elegans (exposure of nematode cultures to [1–9-NαC]-linusorb B3 induced a 30% increase in production of the HSP 70A protein); 3) induce apoptosis in Calu-3 cells; and 4) modulate regulatory genes in microarray analysis. These diverse activities indicate that LOs might induce apoptosis in cancer cells or act as versatile platforms to deliver a variety of biologically active molecules for cancer therapy.

Keywords: flaxseed, linusorb, cyclic peptide, orbitides, heat shock protein, apoptosis, anti-cancer

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Authors: Rafia S. Al-lamki, Jun Wang, Simon Pacey, Jordan Pober, John R. Bradley

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Tumor necrosis factor alpha (TNF), signaling through TNFR2, may act an autocrine growth factor for renal tubular epithelial cells. Clear cell renal carcinomas (ccRCC) contain cancer stem cells (CSCs) that give rise to progeny which form the bulk of the tumor. CSCs are rarely in cell cycle and, as non-proliferating cells, resist most chemotherapeutic agents. Thus, recurrence after chemotherapy may result from the survival of CSCs. Therapeutic targeting of both CSCs and the more differentiated bulk tumor populations may provide a more effective strategy for treatment of RCC. In this study, we hypothesized that TNFR2 signaling will induce CSCs in ccRCC to enter cell cycle so that treatment with ligands that engage TNFR2 will render CSCs susceptible to chemotherapy. To test this hypothesis, we have utilized wild-type TNF (wtTNF) or specific muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF) to treat either short-term organ cultures of ccRCC and adjacent normal kidney (NK) tissue or cultures of CD133+ cells isolated from ccRCC and adjacent NK, hereafter referred to as stem cell-like cells (SCLCs). The effect of cyclophosphamide (CP), currently an effective anticancer agent, was tested on CD133+SCLCs from ccRCC and NK before and after R2TNF treatment. Responses to TNF were assessed by flow cytometry (FACS), immunofluorescence, and quantitative real-time PCR, TUNEL, and cell viability assays. Cytotoxic effect of CP was analyzed by Annexin V and propidium iodide staining with FACS. In addition, we assessed the effect of TNF on isolated SCLCs differentiation using a three-dimensional (3D) culture system. Clinical samples of ccRCC contain a greater number SCLCs compared to NK and the number of SCSC increases with higher tumor grade. Isolated SCLCs show expression of stemness markers (oct4, Nanog, Sox2, Lin28) but not differentiation markers (cytokeratin, CD31, CD45, and EpCAM). In ccRCC organ cultures, wtTNF and R2TNF increase CD133 and TNFR2 expression and promote cell cycle entry whereas wtTNF and R1TNF increase TNFR1 expression and promote cell death of SCLCs. Similar findings are observed in SCLCs isolated from NK but the effect was greater in SCLCs isolated from ccRCC. Application of CP distinctly triggered apoptotic and necrotic cell death in SLCSs pre-treatment with R2TNF as compared to CP treatment alone, with SCLCs from ccRCC more sensitive to CP compared to SLCS from NK. Furthermore, TNF promotes differentiation of SCLCs to an epithelial phenotype in 3D cultures, confirmed by cytokeratin expression and loss of stemness markers Nanog and Sox2. The differentiated cells show positive expression of TNF and TNFR2. These findings provide evidence that selective engagement of TNFR2 drive CSCs to cell proliferation/differentiation, and targeting of cycling cells with TNFR2 agonist in combination with anti-cancer agents may be a potential therapy for RCC.

Keywords: cancer stem cells, ccRCC, cell cycle, cell death, TNF, TNFR1, TNFR2, CD133

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Authors: Maryam Mohammad Hadi, Heather Nesbitt, Hamzah Masood, Hashim Ahmed, Mark Emberton, John Callan, Alexander MacRobert, Anthony McHale, Nikolitsa Nomikou

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Sonodynamic therapy (SDT) utilises ultrasound in combination with sensitizers, such as porphyrins, for the production of cytotoxic reactive oxygen species (ROS) and the confined ablation of tumours. Ultrasound can be applied locally, and the acoustic waves, at frequencies between 0.5-2 MHz, are transmitted efficiently through tissue. SDT does not require highly toxic agents, and the cytotoxic effect only occurs upon ultrasound exposure at the site of the lesion. Therefore, this approach is not associated with adverse side effects. Further highlighting the benefits of SDT, no cancer cell population has shown resistance to therapy-triggered ROS production or their cytotoxic effects. This is particularly important, given the as yet unresolved issues of radiation and chemo-resistance, to the authors’ best knowledge. Another potential future benefit of this approach – considering its non-thermal mechanism of action – is its possible role as an adjuvant to immunotherapy. Substantial pre-clinical studies have demonstrated the efficacy and targeting capability of this therapeutic approach. However, SDT has yet to be fully characterised and appropriately exploited for the treatment of cancer. In this study, a formulation based on multistimulus-responsive sensitizer-containing nanoparticles that can accumulate in advanced prostate tumours and increase the therapeutic efficacy of SDT has been developed. The formulation is based on a polyglutamate-tyrosine (PGATyr) co-polymer carrying hematoporphyrin. The efficacy of SDT in this study was demonstrated using prostate cancer as the translational exemplar. The formulation was designed to respond to the microenvironment of advanced prostate tumours, such as the overexpression of the proteolytic enzymes, cathepsin-B and prostate-specific membrane antigen (PSMA), that can degrade the nanoparticles, reduce their size, improving both diffusions throughout the tumour mass and cellular uptake. The therapeutic modality was initially tested in vitro using LNCaP and PC3 cells as target cell lines. The SDT efficacy was also examined in vivo, using male SCID mice bearing LNCaP subcutaneous tumours. We have demonstrated that the PGATyr co-polymer is digested by cathepsin B and that digestion of the formulation by cathepsin-B, at tumour-mimicking conditions (acidic pH), leads to decreased nanoparticle size and subsequent increased cellular uptake. Sonodynamic treatment, at both normoxic and hypoxic conditions, demonstrated ultrasound-induced cytotoxic effects only for the nanoparticle-treated prostate cancer cells, while the toxicity of the formulation in the absence of ultrasound was minimal. Our in vivo studies in immunodeficient mice, using the hematoporphyrin-containing PGATyr nanoparticles for SDT, showed a 50% decrease in LNCaP tumour volumes within 24h, following IV administration of a single dose. No adverse effects were recorded, and body weight was stable. The results described in this study clearly demonstrate the promise of SDT to revolutionize cancer treatment. It emphasizes the potential of this therapeutic modality as a fist line treatment or in combination treatment for the elimination or downstaging of difficult to treat cancers, such as prostate, pancreatic, and advanced colorectal cancer.

Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound

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Authors: Aliya Sekenova, Vyacheslav Ogay

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The derivation of human induced pluripotent stem cells (iPSCs) from somatic cells by direct reprogramming opens wide perspectives in the regenerative medicine. It means the possibility to develop the personal and, consequently, any immunologically compatible cells for applications in cell-based therapy. The purpose of our study was to develop the technology for the production of NK cells from T cell-derived induced pluripotent stem cells (TiPSCs) for subsequent application in adoptive cancer immunotherapy. Methods: In this study iPSCs were derived from peripheral blood T cells using Sendai virus vectors expressing Oct4, Sox2, Klf4 and c-Myc. Pluripotent characteristics of TiPSCs were examined and confirmed with alkaline phosphatase staining, immunocytochemistry and RT-PCR analysis. For NK cell differentiation, embryoid bodies (EB) formed from (TiPSCs) were cultured in xenogeneic serum-free medium containing human serum, IL-3, IL-7, IL-15, SCF, FLT3L without using M210-B4 and AFT-024 stromal feeder cells. After differentiation, NK cells were characterized with immunofluorescence analysis, flow cytometry and cytotoxicity assay. Results: Here, we for the first time demonstrate that TiPSCs can effectively differentiate into functionally active NK cells without M210-B4 and AFT-024 xenogeneic stroma cells. Immunofluorescence and flow cytometry analysis showed that EB-derived cells can differentiate into a homogeneous population of NK cell expressing high levels of CD56, CD45 and CD16 specific markers. Moreover, these cells significantly express killing activation receptors such as NKp44 and NKp46. In the comparative analysis, we observed that NK cells derived using feeder-free culture system have more high killing activity against K-562 tumor cells, than NK cells derived by feeder-dependent method. Thus, we think that our obtained data will be useful for the development of large-scale production of NK cells for translation into cancer immunotherapy.

Keywords: induced pluripotent stem cells, NK cells, T cells, cell diffentiation, feeder cell-free culture system

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Authors: Firas Rashad Al-Samarai

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Introduction: Benign prostatic hyperplasia (BPH) is a common condition as men get older. An enlarged prostate gland can cause uncomfortable urinary symptoms, such as blocking the flow of urine out of the bladder. It can also cause bladder, urinary tract, or kidney problems. Objective: to evaluate the efficacy and interaction of tamsulosin with finasteride treatment on induced benign prostate hyperplasia (BPH) in mice. Methods: BPH was induced by subcutaneous injection of testosterone propionate (20 mg/kg) for 30 days. Eighty-five mice were divided into five groups. The first group (G1): twenty-five mice induced BPH treated with tamsulosin orally and divided into five equal subgroups with doses (0.017, 0.052, 0.087, 0. 123, and 0.158) mg/kg, the second group (G2): twenty-five mice induced BPH treated with finasteride orally and divided into five equal subgroups with doses (0.175, 0.527, 0.878, 1.23, and 1.580) mg/kg. the third group (G3): twenty-five mice induced BPH treated with a combination of tamsulosin with finasteride orally, and divided into five equal subgroups with doses (0.0085, 0.0875), (0.026, 0.2635), (0.0435, 0.439) , (0.0615, 0.615) and ( 0.079 , 0.790 ) mg/kg respectively. Fourth group (G4): five mice induced BPH and treated distilled water. Fifth group (G5): five mice were not inducing BPH and without any treatment. Results: The results showed a gradual significant increase in prostate weight % and prostate index % Inhibitions until reached saturation in the last two doses of tamsulosin, finasteride, and combination groups, the maximum effective dose of tamsulosin and finasteride were (0.156) and (1.495) mg/kg respectively. Moreover, the effective dose of the combination (tamsulosin and finasteride) was estimated (0.06876, 0.6876) mg/kg, respectively, as well as the type of interaction was synergism and the value of the combination index was 0.046. Conclusions: We concluded that the combination of tamsulosin with finasteride showed a synergistic effect in BPH treatment by minimizing the side effect of each drug as s result of decreasing the dose of each one.

Keywords: Tamsulosin, Finasteride, combination, BPH

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Authors: R. D. Esposito, V. M. Barberá, P. García Morales, P. Dorado Rodríguez, J. Sanz, M. Fuentes, D. Planes Meseguer, M. Saceda, L. Fernández Fornos, M. P. Ventero

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Results obtained by our group on glioblastoma multiforme (GBM) primary cultures , show a dramatic potentiation of radiation effects when 2 units/ml of D-amino acid oxidase (DAO) enzyme are added, free or immobilized in magnetic nanoparticles, to irradiated samples just after the irradiation. Cell cultures were exposed to radiation doses of 7Gy and 15Gy of 6 MV photons from a clinical linear accelerator. At both doses, we observed a clear enhancing effect of radiation-induced damages due to the addition of DAO.

Keywords: D-amino Acid Oxidase (DAO) enzyme, magnetic particles, nanotechnology, radiation therapy enhancement

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Authors: Dominika Pihikova, Stefan Belicky, Tomas Bertok, Roman Sokol, Petra Kubanikova, Jan Tkac

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Since aberrant glycosylation is frequently accompanied by both physiological and pathological processes in a human body (cancer, AIDS, inflammatory diseases, etc.), the analysis of tumor-associated glycan patterns have a great potential for the development of novel diagnostic approaches. Moreover, altered glycoforms may assist as a suitable tool for the specificity and sensitivity enhancement in early-stage prostate cancer diagnosis. In this paper we discuss the construction and optimization of ultrasensitive sandwich biosensor platform employing lectin as glycan-binding protein. We focus on the immunoassay development, reduction of non-specific interactions and final glycoprofiling of human serum samples including both prostate cancer (PCa) patients and healthy controls. The fabricated biosensor was measured by label-free electrochemical impedance spectroscopy (EIS) with further lectin microarray verification. Furthermore, we analyzed different biosensor interfaces with atomic force microscopy (AFM) in nanomechanical mapping mode showing a significant differences in the altitude. These preliminary results revealing an elevated content of α-2,3 linked sialic acid in PCa patients comparing with healthy controls. All these experiments are important step towards development of point-of-care devices and discovery of novel glyco-biomarkers applicable in cancer diagnosis.

Keywords: biosensor, glycan, lectin, prostate cancer

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Authors: O. C. Abbah, O. Obidoa, J. Omale

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Prostate tumor is fast becoming a leading cause of morbidity and mortality in human male adults, with 50 percent of men aged 50 years and above having histological evidence of the benign tumor. The study was set out to undertake phytochemical screening and proximate analysis of the pulp of A. muricata fruit - soursop; to determine the acute toxicity of the fruit pulp extract and its effect on male albino Wistar rats with concurrent induction of experimental benign prostate hyperplasia (BPH). Eighteen rats (average weight of 100g) were used for the lethality studies and were orally administered graded doses of aqueous extracts of the fruit pulp up to 5000 mg/kg body weight. Twenty five rats weighing 150-200g were divided into five groups of five rats each for the tumor studies. The groups included four controls – Hormone control, HC, which took Testosterone, T; and Estradiol, E2 – only, in olive oil as vehicle; Vehicle control, VC; Soursop control, SC, which received the extract only; VS, Vehicle and Soursop – and the Test group, TG (500mg/kg b.w.). All rats were dosed orally. Tumor was induced with exogenous Testosterone propionate: Estradiol valerate at 300µg: 80µg/kg b.w. (respectively) in olive oil, administered subcutaneously in the inguinal region of the rats on alternate days for 21 days. Administration of the fruit pulp at graded doses up to 5000mg/kg resulted in no lethality even after 72 hours. Results from tumor studies revealed that the administration of the fruit extracts significantly (p < 0.05) reduced the relative prostate weight of the TG compared with the HC, with values of 006±0.001 and 0.010±0.003 respectively. Treatment with vehicle, soursop and vehicle with soursop caused no significant (p>0.05) change in prostate size, with their respective relative prostate weights being 0.002±0.001, 0.004±0.002 and 0.002±0.001 compared with TG. Also, treatment with A. muricata fruit extract significantly decreased (p < 0.05) serum prostate specific antigen, PSA, in TG compared with HC, with values 0.055±0.017 and 0.194±0.068 ng/ml respectively. Furthermore, A. muricata administration displayed Testosterone boosting, Estradiol lowering and consequently testosterone-estradiol ratio increasing potential at the end of the 21 days. The preventive property of soursop against experimental BPH was corroborated by histological evidence in this study. The study concludes that A. muricata fruit holds a great potential for benign prostate tumor prevention and, possibly, management.

Keywords: annona muricata, benign prostate tumor, hormone, preventive potential, soursop

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Authors: Ceyda Okudu, Secil Eroglu, Khandakar A. S. M. Saadat, Sibel O. Balci

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Ring Finger Protein 2 (RNF2) is a member of polycomb repressive complex 1 (PRC1), which is one of the epigenetic regulators in the genome. When RNF2 combines with other PRC1 members, it mediates the mono-ubiquitination of Histon2A (H2A). In breast cancer, RNF2 is commonly overexpressed, and also it promotes metastasis and invasion in other aggressive tumors like melanoma, prostate, and hepatocarcinoma. The role of RNF2 in the metastasis and invasion of breast cancer has not yet been elucidated. Our aim is to observe the role of RNF2 in metastasis and invasion in this study by miRNA mediated RNF2 gene silencing in breast cancer cell lines. We selected miRNAs, targeting to RNF2 by searching online databases. miR-17-5p, miR20a-5p, and miR-106b-5p were transfected to breast cancer cell lines (MCF-7, MDA-MB-231, SK-BR-3, and ZR-75-1), and also we used normal breast epithelial cell line (hTERT-HME1) to compare RNF2 gene expression level. After 48-72 hours post-transfection, mRNAs were isolated from the cells, and gene expressions were measured by RT-qPCR after from cDNA syntheses. We observed that RNF2 was highly expressed in SK-BR-3 and MDA-MB-231 cell lines opposite to MCF-7 and ZR-75-1 cell lines. RNF2 was downregulated 5, 5 and 7 fold by miR17-5p, miR20a-5p and miR106b-5p respectively in MCF-7. However, in SK-BR-3 and ZR-75-1 cell lines, miRNAs did not affect significantly RNF2 gene expression level. miR20a-5p decreased RNF2 3 fold and miR17-5p and miR106b-5p did not affect MDA-MB-231. After gene expression analysis, we performed metastasis and invasion assay in MCF-7 cells. For metastasis, we used both wound healing assay and Transwell Cell Migration Assay, and we used Transwell Cell Invasion Assay for invasion. The data of this assay showed that miR17-5p and miR20a-5p decreased both invasion and metastasis level, but miR106b-5p has no effect. We would like to conclude that RNF2 can be targeted by miR17-5p, miR20a-5p and miR106b-5p in MCF-7 cells and also RNF2, which is one of the upregulated genes in aggressive tumor, can be decreased by using these miRNAs. In future, we would like to confirm these results at the protein level and also whether these miRNAs are direct target of RNF2 or not.

Keywords: breast cancer, epigenetic, microRNAs, RNF2

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Authors: Reyhane Hamed Kamran

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Early stage morphogenesis requires the execution of complex systems that direct the nearby conduct of gatherings of cells. The organization of such instruments has been, for the most part, deciphered through the recognizable proof of moderated groups of flagging pathways that spatially and transiently control cell conduct. In any case, how this data is handled to control cell shape and cell elements is an open territory of examination. The structure that rises up out of differing controls, for example, cell science, material science, and formative science, focuses to bond and cortical actin arranges as controllers of cell surface mechanics. In this specific circumstance, a scope of formative marvels can be clarified by the guideline of cell surface pressure.

Keywords: cell, tissue damage, morphogenesis, cell conduct

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Authors: Narin Salehiyan

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Early stage morphogenesis requires the execution of complex systems that direct the nearby conduct of gatherings of cells. The organization of such instruments has been, for the most part, deciphered through the recognizable proof of moderated groups of flagging pathways that spatially and transiently control cell conduct. In any case, how this data is handled to control cell shape and cell elements is an open territory of examination. The structure that rises up out of differing controls, for example, cell science, material science and formative science, focuses to bond and cortical actin arranges as controllers of cell surface mechanics. In this specific circumstance, a scope of formative marvels can be clarified by the guideline of cell surface pressure.

Keywords: cell, tissue damage, morphogenesis, cell conduct

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Authors: Carles Ferré, Ferran Llopis, Javier Jacob, Jordi Giol, Xavier Palom, Ignasi Bardés

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Objective: To analyze the characteristics of acute bacterial prostatitis (ABP) in elderly patients attended in the emergency department (ED). Methods: Observational and cohort study with prospective follow-up including patients with ABP presenting to the ED from January-December 2012. Data were collected for demographic variables, comorbidities, clinical and microbiological findings, treatment, outcome, and reconsultation at 30 days follow up. Findings were compared between patients ≥ 75 years (study group) and < 75 years (control group). Results: During the study period 241 episodes of ABP were included for analysis. Mean age was 62,9 ± 16 years, and 64 (26.5%) were ≥ 75 years old. A history of prostate adenoma was reported in 54 cases (22,4%), diabetes mellitus in 47 patients (19,5%) and prior manipulation of the lower urinary tract in 40 (17%). Mean symptoms duration was 3.38 ± 4.04 days, voiding symptoms were present in 176 cases (73%) and fever in 154 (64%). From 216 urine cultures, 128 were positive (59%) and 24 (17,6%) out of 136 blood cultures. Escherichia coli was the main pathogen in 58.6% of urine cultures and 64% of blood cultures (with resistant strains to fluoroquinolones in 27,7%, cotrimoxazole in 22,9% and amoxicillin/clavulanic in 27.7% of cases). Seventy patients (29%) were admitted to the hospital, and 3 died. At 30-day follow-up, 29 patients (12%) returned to the ED. In the bivariate analysis previous manipulation of the urinary tract, history of cancer, previous antibiotic treatment, resistant E. coli strains to amoxicillin-clavulanate and ciprofloxacin and extended spectrum beta-lactamase (ESBL) producers, renal impairment, and admission to the hospital were significantly more frequent (p < 0.05) among patients ≥ 75 years compared to those younger than 75 years. Conclusions: Ciprofloxacin and amoxicillin-clavulanate appear not to be good options for the empiric treatment of ABP for patients ≥ 75 years given the drug-resistance pattern in our series, and the proportion of ESBL-producing strains of E. coli should be taken into account. Awaiting bacteria identification and antibiogram from urine and/or blood cultures, treatment on an inpatient basis should be considered in older patients with ABP.

Keywords: acute bacterial prostatitits, antibiotic resistance, elderly patients, emergency

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Authors: Alok Nahata

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Introduction: Nowadays, androgen-mediated diseases such as prostate cancer, hirsutism, acne, androgenic alopecia and benign prostatic hyperplasia (BPH) have become serious problems. The aim of the present study was to find out whether Ganoderma lucidum (GL) can be used as a clinically effective medicine for the management of prostatic hyperplasia. Methodology: In vitro studies were conducted to assess the 5α-reductase inhibitory potential of GL. Testosterone (3 mg/kg s.c.) was administered to the rats along with the test extracts (10, 20 and 50 mg/kg p.o for a period of 28 days. Finasteride was used as a positive control (1 mg/kg p.o.). Major Findings: GL extracts attenuated the increase in the prostate/body weight ratio (P/BW) induced by testosterone. Most of the values were significant when compared to testosterone-treated group and finasteride treated groups. Petroleum ether extract (50 mg/kg p.o.) exhibited the best activity (P < 0.01). Ethanolic extract (20 and 50 mg/kg p.o.) also exhibited significant activity (P < 0.01). The urine output also improved significantly (P < 0.01 in all groups as compared to standard finasteride), which emphasize the clinical implications of the study. Testosterone levels measured weekly and prostate-specific antigen (PSA) levels measured at the end of the study also support the findings. Histological studies suggested improvement in prostatic histoarchitecture in extract-treated groups as compared to the testosterone-treated group. Conclusion: Study clearly reflects the utility of extracts in BPH. Because of conversion of testosterone to dihydrotestosterone, the prostate size is increased, thereby causing obstruction in urinary output. The observed effect that extracts do not allow the increase as reflected by urinary output, P/BW ratios and histoarchitecture showed that activity of administered testosterone was blocked by the extract and resulted in recovery.

Keywords: benign prostatic hyperplasia, Ganoderma lucidum, prostate-specific antigen, 5α-reductase, testosterone

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Authors: N. Mesatywa

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The aim of the article is to emphasize and motivate for the role of integrating cultures in institutions of learning. The article has used a literature review methodology. Findings indicate that cultures espouse immense social capital that can: facilitate and strengthen moral education that will help learners in mitigating moral decadence and HIV/AIDS; embrace and strengthen the tenets of peace and tranquility among learners from different backgrounds; can form education against xenophobia; can facilitate the process of cultural paradigm shift that will slow down cultural attrition and decadence; can bring back cultural strength, cultural revival, cultural reawakening and cultural emancipation, etc. The article recommends governments to finance cultural activities in institutions of learning; to allow cultural practitioners to be part and parcel of cultural education; and challenge people to pride in the social capital of their indigenous cultures.

Keywords: cultures, cultural practitioners, integration, traditional healers

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Authors: Yu-Mei Hsueh, Wei-Jen Chen, Yung-Kai Huang, Cheng-Shiuan Tsai, Kuo-Cheng Yeh

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Prostate cancer occurs in men over the age of 50, and rank sixth of the top ten cancers in Taiwan, and the incidence increased gradually over the past decade in Taiwan. Arsenic is confirmed as a carcinogen by International Agency for Research on (IARC). Arsenic induces oxidative stress may be a risk factor for prostate cancer, but the mechanism is not clear. Selenium is an important antioxidant element. Whether the association between plasma selenium levels and risk of prostate cancer are modified by different genotype of selenoprotein is still unknown. Glutathione peroxidase, selenoprotein P (SEPP1) and 15 kDa selenoprotein (SEP 15) are selenoprotein and regulates selenium transport and the oxidation and reduction reaction. However, the association between gene polymorphisms of selenoprotein and prostate cancer is not yet clear. The aim of this study is to determine the relationship between plasma selenium, polymorphism of selenoprotein, urinary total arsenic concentration and prostate cancer. This study is a hospital-based case-control study. Three hundred twenty-two cases of prostate cancer and age (±5 years) 1:1 matched 322 control group were recruited from National Taiwan University Hospital, Taipei Medical University Hospital, and Wan Fang Hospital. Well-trained personnel carried out standardized personal interviews based on a structured questionnaire. Information collected included demographic and socioeconomic characteristics, lifestyle and disease history. Blood and urine samples were also collected at the same time. The Research Ethics Committee of National Taiwan University Hospital, Taipei, Taiwan, approved the study. All patients provided informed consent forms before sample and data collection. Buffy coat was to extract DNA, and the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) was used to measure the genotypes of SEPP1 rs3797310, SEP15 rs5859, GPX1 rs1050450, GPX2 rs4902346, GPX3 rs4958872, and GPX4 rs2075710. Plasma concentrations of selenium were determined by inductively coupled plasma mass spectrometry (ICP-MS).Urinary arsenic species concentrations were measured by high-performance liquid chromatography links hydride generator and atomic absorption spectrometer (HPLC-HG-AAS). Subject with high education level compared to those with low educational level had a lower prostate cancer odds ratio (OR) Mainland Chinese and aboriginal people had a lower OR of prostate cancer compared to Fukien Taiwanese. After adjustment for age, educational level, subjects with GPX1 rs1050450 CT and TT genotype compared to the CC genotype have lower, OR of prostate cancer, the OR and 95% confidence interval (Cl) was 0.53 (0.31-0.90). SEPP1 rs3797310 CT+TT genotype compared to those with CC genotype had a marginally significantly lower OR of PC. The low levels of plasma selenium and the high urinary total arsenic concentrations had the high OR of prostate cancer in a significant dose-response manner, and SEPP1 rs3797310 genotype modified this joint association.

Keywords: prostate cancer, plasma selenium concentration, urinary total arsenic concentrations, glutathione peroxidase, selenoprotein P, selenoprotein 15, gene polymorphism

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Authors: Shangqing Song, Bin Xu, Yajun Cheng, Zhong Wang

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miRNAs derived from exosomes exist in a body fluid such as urine were regarded as potential biomarkers for various human cancers diagnosis and prognosis, as mature miRNAs can be steadily preserved by exosomes. However, its potential value in clear cell renal cell carcinoma (ccRCC) diagnosis and prognosis remains unclear. In the present study, differentially expressed miRNAs from urinal exosomes were identified by next-generation sequencing (NGS) technology. The 16 differentially expressed miRNAs were identified between ccRCC patients and healthy donors. To explore the specific diagnosis biomarker of ccRCC, we validated these urinary exosomes from 70 early-stage renal cancer patients, 30 healthy people and other urinary system cancers, including 30 early-stage prostate cancer patients and 30 early-stage bladder cancer patients by qRT-PCR. The results showed that urinary exosome miR-30c-5p could be stably amplified and meanwhile the expression of miR-30c-5p has no significant difference between other urinary system cancers and healthy control, however, expression level of miR-30c-5p in urinary exosomal of ccRCC patients was lower than healthy people and receiver operation characterization (ROC) curve showed that the area under the curve (AUC) values was 0.8192 (95% confidence interval was 0.7388-0.8996, P= 0.0000). In addition, up-regulating miR-30c-5p expression could inhibit renal cell carcinoma cells growth. Lastly, HSP5A was found as a direct target gene of miR-30c-5p. HSP5A depletion reversed the promoting effect of ccRCC growth casued by miR-30c-5p inhibitor, respectively. In conclusion, this study demonstrated that urinary exosomal miR-30c-5p is readily accessible as diagnosis biomarker of early-stage ccRCC, and miR-30c-5p might modulate the expression of HSPA5, which correlated with the progression of ccRCC.

Keywords: clear cell renal cell carcinoma, exosome, HSP5A, miR-30c-5p

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Authors: Ana M. Lara, Manuela Llano, Felipe Gaitán, Rosa H. Bustos, Ana Maria Perdomo-Arciniegas, Ximena Bonilla

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Umbilical cord blood is used as a source of progenitor and stem cells for the regeneration of the hematopoietic and immune system to treat patients with different hematological or non-hematological diseases. This stem cell source represents an advantage over the use of bone marrow or mobilized peripheral blood because it has a lower incidence rate of graft-versus-host disease, probably due to fewer immunological compatibility restrictions. However, its low cellular dose limits its use in pediatric patients. This work proposes the standardization of a cell expansion technique to compensate for the dose of infused cells through the ex-vivo manipulation of hematopoietic progenitor cells from umbilical cord blood before transplantation. The expansion model is carried out through co-cultures with mesenchymal stem cells (MSC) from bone marrow (BM) and less explored fetal tissues such as Wharton's jelly (WJ) and umbilical cord blood (UCB). Initially, a master cell bank of primary mesenchymal stem cells isolated from different sources was established and characterized following International Society of Cell Therapies (ISCT) indications. Additionally, we assessed the effect of a short 25 Gy cycle of gamma irradiation on cell cycle arrest of mesenchymal cells over the support capacity for the expansion of hematopoietic stem cells from umbilical cord blood was evaluated. The results show that co-cultures with MSC from WJ and UCB allow the cellular dose of HSPC to be maximized between 5 and 16 times having a similar support capacity as BM. In addition, was evaluated the hematopoietic stem progenitor cell's HSPC functionality through the evaluation of migration capacity, their differentiation capacity during culture time by flow cytometry to evaluate the expression of membrane markers associated with lineage-committed progenitors, their clonogenic potential, and the evaluation of secretome profile in the expansion process was evaluated. So far, the treatment with gamma irradiation maintains the hematopoietic support capacity of mesenchymal stem cells from the three sources studied compared to treatments without irradiation, favoring the use of fetal tissues that are generally waste to obtain mesenchymal cell lines for ex-vivo expansion systems. With the results obtained, a standardized protocol that will contribute to the development of ex-vivo expansion with MSC on a larger scale will be achieved, enabling its clinical use and expanding its application in adults.

Keywords: ex-vivo expansion, hematopoietic stem cells, hematopoietic stem cell transplantation, mesenchymal stem cells, umbilical cord blood

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Authors: Roberto Coppo, Francesca Orso, Daniela Dettori, Elena Quaglino, Lei Nie, Mehran M. Sadeghi, Daniela Taverna

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Malignant melanoma is currently the fifth most common cancer in the white population and it is fatal in its metastatic stage. Several research studies in recent years have provided evidence that cancer initiation and progression are driven by genetic alterations of the tumor and paracrine interactions between tumor and microenvironment. Scattered data show that the Endothelial and Smooth muscle cell-Derived Neuropilin-like molecule (ESDN) controls cell proliferation and movement of stroma and tumor cells. To investigate the role of ESDN in the tumor microenvironment during melanoma progression, murine melanoma cells (B16 or B16-F10) were injected in ESDN knockout mice in order to evaluate how the absence of ESDN in stromal cells could influence melanoma progression. While no effect was found on primary tumor growth, increased cell extravasation and lung metastasis formation was observed in ESDN knockout mice compared to wild type controls. In order to understand how cancer cells cross the endothelial barrier during metastatic dissemination in an ESDN-null microenvironment, structure, and permeability of lung blood vessels were analyzed. Interestingly, ESDN knockout mice showed structurally altered and more permeable vessels compared to wild type animals. Since cell surface molecules mediate the process of tumor cell extravasation, the expression of a panel of extravasation-related ligands and receptors was analyzed. Importantly, modulations of N-cadherin, E-selectin, ICAM-1 and VAP-1 were observed in ESDN knockout endothelial cells, suggesting the presence of a favorable tumor microenvironment which facilitates melanoma cell extravasation and metastasis formation in the absence of ESDN. Furthermore, a potential contribution of immune cells in tumor dissemination was investigated. An increased recruitment of macrophages in the lungs of ESDN knockout mice carrying subcutaneous B16-F10 tumors was found. In conclusion, our data suggest a functional role of ESDN in the tumor microenvironment during melanoma progression and the identification of the mechanisms that regulate tumor cell extravasation could lead to the development of new therapies to reduce metastasis formation.

Keywords: melanoma, tumor microenvironment, extravasation, cell surface molecules

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Authors: Harley Stephens

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Although fiducial marker insertion is regarded as the ‘gold standard’ in terms of image guided radiotherapy (IGRT), its application must be considered carefully as the procedure can be invasive, time-consuming, and reliant on consultant expertise. Precision of the fiducials is dependent on these markers remaining in the same location and on the prostate not changing shape during the course treatment. To facilitate the acquirement of non-ionising IGRT and intra-fractional prostate tracking, Clarity TPUS was developed as an alternative imaging system. The main benefits of Clarity TPUS are that it is non-invasive, non-ionising and cost-effective. Other studies have compared fiducials to transabdominal ultrasound, which has since been proven to not be as accurate as trans-perineal imaging, as included in this study. CBCT fiducial translations and Clarity TPUS translations for 120 images as part of the PACE-C prostate SABR trial were retrospectively evaluated by three imaging specialists. Differences were analysed using correlation and Bland-Altman plots. Inter-observer matches agreed within 3mm 88.3 % of the time in left/right direction, 86.7 % of the time in in superior/inferior direction, and 91.7% of the time in ant/post direction. They agreed within 5mm more than 98.3 % of the time in all directions. The intra-class correlation co-efficient was calculated for each direction to show agreement between imaging specialist for inter-observer variability. Each was 0.95 or above, with 1 indicating perfect reliability. Agreement between observers was slightly higher for CBCT and fiducials at 98.7% agreement within 5 mm, compared to clarity TPUS where 96.7% agreement was seen within 5mm. Clarity TPUS has the benefit of no additional dose and intra-fractional monitoring, and results show a good correlation between the different modalities. Inter-observer variability is to be considered, and further research with a larger population would be of benefit.

Keywords: oncology, prostate radiotherapy, image guided radiotherapy, IGRT

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Authors: Madiha Liaqat, Rehan Ahmed Khan, Shahid Kamal

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Multiple imputation with delta adjustment is a versatile and transparent technique for addressing univariate missing data in the presence of various missing mechanisms. This approach allows for the exploration of sensitivity to the missing-at-random (MAR) assumption. In this review, we outline the delta-adjustment procedure and illustrate its application for assessing the sensitivity to deviations from the MAR assumption. By examining diverse missingness scenarios and conducting sensitivity analyses, we gain valuable insights into the implications of missing data on our analyses, enhancing the reliability of our study's conclusions. In our study, we focused on assessing logPSA, a continuous biomarker in incomplete prostate cancer data, to examine the robustness of conclusions against plausible departures from the MAR assumption. We introduced several approaches for conducting sensitivity analyses, illustrating their application within the pattern mixture model (PMM) under the delta adjustment framework. This proposed approach effectively handles missing data, particularly loss to follow-up.

Keywords: loss to follow-up, incomplete response, multiple imputation, sensitivity analysis, prostate cancer

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Authors: Hossein Pourbashash

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Recent experimental studies have shown that HIV can be transmitted directly from cell to cell when structures called virological synapses form during interactions between T cells. In this article, we describe a new within-host model of HIV infection that incorporates two mechanisms: infection by free virions and the direct cell-to-cell transmission. We conduct the local and global stability analysis of the model. We show that if the basic reproduction number R0 1, the virus is cleared and the disease dies out; if R0 > 1, the virus persists in the host. We also prove that the unique positive equilibrium attracts all positive solutions under additional assumptions on the parameters.

Keywords: HIV virus model, cell-to-cell transmission, global stability, Lyapunov function, second compound matrices

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Authors: Muhammad Waleed Asfandyar, Akhtar Ahmed, Syed Adib-ul-Hasan Rizvi

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Objective: To evaluate the ability of serum concentration of prostate specific antigen between two cutting points considering it as a predictor of skeletal metastasis on bone scintigraphy in men with prostate cancer. Settings: This study was carried out in department of Nuclear Medicine at Sindh Institute of Urology and Transplantation (SIUT) Karachi, Pakistan. Materials and Method: From August 2013 to November 2013, forty two (42) consecutive patients with prostate cancer who underwent technetium-99m methylene diphosphonate (Tc-99mMDP) whole body bone scintigraphy were prospectively analyzed. The information was collected from the scintigraphic database at a Nuclear medicine department Sindh institute of urology and transplantation Karachi Pakistan. Patients who did not have a serum PSA concentration available within 1 month before or after the time of performing the Tc-99m MDP whole body bone scintigraphy were excluded from this study. A whole body bone scintigraphy scan (from the toes to top of the head) was performed using a whole-body Moving gamma camera technique (anterior and posterior) 2–4 hours after intravenous injection of 20 mCi of Tc-99m MDP. In addition, all patients necessarily have a pathological report available. Bony metastases were determined from the bone scan studies and no further correlation with histopathology or other imaging modalities were performed. To preserve patient confidentiality, direct patient identifiers were not collected. In all the patients, Prostate specific antigen values and skeletal scintigraphy were evaluated. Results: The mean age, mean PSA, and incidence of bone metastasis on bone scintigraphy were 68.35 years, 370.51 ng/mL and 19/42 (45.23%) respectively. According to PSA levels, patients were divided into 5 groups < 10ng/mL (10/42), 10-20 ng/mL (5/42), 20-50 ng/mL (2/42), 50-100 (3/42), 100- 500ng/mL (3/42) and more than 500ng/mL (0/42) presenting negative bone scan. The incidence of positive bone scan (%) for bone metastasis for each group were O1 patient (5.26%), 0%, 03 patients (15.78%), 01 patient (5.26%), 04 patients (21.05%), and 10 patients (52.63%) respectively. From the 42 patients 19 (45.23%) presented positive scintigraphic examination for the presence of bone metastasis. 1 patient presented bone metastasis on bone scintigraphy having PSA level less than 10ng/mL, and in only 1 patient (5.26%) with bone metastasis PSA concentration was less than 20 ng/mL. therefore, when the cutting point adopted for PSA serum concentration was 10ng/mL, a negative predictive value for bone metastasis was 95% with sensitivity rates 94.74% and the positive predictive value and specificities of the method were 56.53% and 43.48% respectively. When the cutting point of PSA serum concentration was 20ng/mL the observed results for Positive predictive value and specificity were (78.27% and 65.22% respectively) whereas negative predictive value and sensitivity stood (100% and 95%) respectively. Conclusion: Results of our study allow us to conclude that serum PSA concentration of higher than 20ng/mL was the most accurate cutting point than a serum concentration of PSA higher than 10ng/mL to predict metastasis in radionuclide bone scintigraphy. In this way, unnecessary cost can be avoided, since a considerable part of prostate adenocarcinomas present low serum PSA levels less than 20 ng/mL and for these cases radionuclide bone scintigraphy could be unnecessary.

Keywords: bone scan, cut off value, prostate specific antigen value, scintigraphy

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Authors: Xi Yu, Lili Gu, Huizhu Wang, Xiao Wei, Dandan Sheng, Xiaoyan Jiang, Min Hong

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Introduction: Hypersensitivity disease is difficult to cure completely because of its recurrence, yupingfengsan (YPFS) is used to treat the diseases with the advantage of reducing the recurrence,but the precise mechanism is not clear. Previous studies of our laboratory have shown that the extract of YPFS can inhibit Th2-type allergic contact dermatitis(ACD) induced by FITC.Besides, thymic stromal lymphopoietin(TSLP) have been proved to be a master switch for allergic inflammation. Based on these studies, we want to establish a mouse model of TSLP production based on Th2 cell-mediated allergic inflammation to explore the regulating mechanisms of YPFS on TSLP in Th2 cell-mediated allergic inflammation. Methods: Th2-type ACD mouse model: The mice were topically sensitized on the abdomens (induction phase) and elicited on its ears skin 6 day later (excitation phase) with FITC solution, and the ear swelling was measured to evaluate the allergic inflammation；A mouse model of TSLP production based on Th2 cell-mediated allergic inflammation (TSLP production model): the skin of the ear was sensitized on two consecutive days with FITC solution causing the production of TSLP；Mice were treated with YPFS extract，ELISA、Real-time PCR and Western-blotting were using to examine the mRNA and protein levels of TSLP\TSLPR and TLRs ect. Results: YPFS extract can attenuates Th2-type allergic inflammatory in mice；in TSLP production model, YPFS can inhibit the expression of TSLP、 TSLPR、TLRs and MyD88, So we deduce the possible mechanisms of YPFS to play a role of intervention is through TLRs- MyD88 dependent and independent pathway to reduce TSLP production.

Keywords: YPFS, TSLP, TLRs, Th2-type allergic contact dermatitis

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Authors: Yi Meng, YunGao

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Having been studied and worked in North America and Europe, we, two Chinese art educators, have been enormously influenced by eastern and western cultures. Thus, we aim to enhance students’ learning experiences by exploring and amalgamating both cultures for art creating. This text draws on our action research study of students’ visual literacy practices in a foundation sketching course in a major Chinese university, exploring art forms by cross-utilizing various cultural aspects. Instead of relying on the predominant western observational drawing skills in our classroom, we taught students about ancient Chinese art in the provincial museum, using Fu Hao owl-shaped vessel, a Shang Dynasty national treasure, as the final sketch project of this course. We took up multimodal literacy, which emphasized students’ critical use of creativity to exploit the semiotic potentials of communicative modes to address diverse cultural issues through their multimodal design. We used the Hong Kong-based artist Tik Ka’s artworks to demonstrate the cultural amalgamation of Chinese traditions and western pop cultures. Collectively, these approaches create a dialogical space for students to experience, analyze, and negotiate with complex modes and potentially transform their understanding of both cultures by redesigning Fu Hao.

Keywords: Chinese traditions, western pop cultures, Fu Hao, arts education, design sketch

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Authors: C. M. Williams, R. English, P. King, I. M. Brown

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Introduction: Pseudoangiomatous Stromal Hyperplasia (PASH) is a benign fibrous proliferation of breast stroma affecting predominantly premenopausal women with no significant increased risk of breast cancer. Informal recommendations for management have continued to evolve over recent years from surgical excision to observation, although there are no specific national guidelines. This study assesses the safety of a non-surgical approach to PASH management by review of cases at a single centre. Methods: Retrospective case series review (January 2011 – August 2016) was conducted on consecutive PASH cases. Diagnostic classification (clinical, radiological and histological), management outcomes, and breast cancer incidence were recorded. Results: 43 patients were followed up for median of 25 months (3-64) with 75% symptomatic at presentation. 12% of cases (n=5) had a radiological score (BIRADS MMG or US) ≥ 4 of which 3 were confirmed malignant. One further malignancy was detected and proven radiologically occult and contralateral. No patients were diagnosed with a malignancy during follow-up. Treatment evolved from 67% surgical in 2011 to 33% in 2016. Conclusions: The management of PASH has transitioned in line with other published experience. The preliminary findings suggest this appears safe with no evidence of missed malignancies; however, longer follow up is required to confirm long-term safety. Recommendations: PASH with suspicious radiological findings ( ≥ U4/R4) warrants multidisciplinary discussion for excision. In the absence of histological or radiological suspicion of malignancy, PASH can be safely managed without surgery.

Keywords: benign breast disease, conservative management, malignancy, pseudoangiomatous stromal hyperplasia, surgical excision

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