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Jungyoon Choi, Emilie Rustique, Maxime Henry, Mélanie Guidetti, Véronique Josserand, Lucie Sancey, Jérôme Boutet, Jean-Luc Coll
Like several 50nm-large nanocarriers, lipid nanoparticles (LNPs) can passively accumulate in tumors through the Enhanced Permeability and Retention effect. In this study, we developed PEGylated LNPs loaded with IR780 iodide as a contrast agent for NIR fluorescence imaging and modified them with cyclic RGD peptides in order to target integrin avβ3. We demonstrate a specific targeting of the receptor with cRGD-LNPs but not with cRAD-LNP and standard LNP using HEK293(β3), HEK293(β3)-αvRFP, DU145 and PC3 cell lines...
March 6, 2017: International Journal of Pharmaceutics
Akiko Harada, Junji Uchino, Taishi Harada, Noriaki Nakagaki, Junko Hisasue, Masaki Fujita, Koichi Takayama
Malignant mesothelioma (MM) incidence is increasing drastically worldwide as an occupational disease resulting from asbestos exposure. However, no curative treatment for MM of advanced stage is available. Thus, new therapeutic approaches for MM are required. Because malignant pleural mesothelioma (MPM) cells spread along the pleural surface in most patients, MPM can be targeted using intrapleural therapeutic approaches. In this study, we investigated the effectiveness of the intrapleural instillation of a replication-competent adenovirus as an oncolytic agent against MPM...
January 2017: Cancer Science
Shi Deng, Tao Jin, Li Zhang, Hong Bu, Peng Zhang
Chronic renal allograft dysfunction (CRAD) is the most common cause of graft failure following renal transplantation. However, the underlying mechanisms remain to be fully elucidated. Immunosuppressants and hyperlipidemia are associated with renal fibrosis following long‑term use. The present study aimed to determine the effects of tacrolimus (FK506) and lipid metabolism disorder on CRAD. In vitro and in vivo models were used for this investigation. Cells of the mouse proximal renal tubular epithelial cell strain, NRK‑52E, were cultured either with oxidized low‑density lipoprotein (ox‑LDL), FK506, ox‑LDL combined with FK506, or vehicle, respectively...
November 2016: Molecular Medicine Reports
Q Yan, H Jiang, B Wang, W Sui, H Zhou, G Zou
BACKGROUND: To investigate the expression of RANTES (regulated upon activation, normal T-cell-expressed and -secreted) and monocyte chemoattractant protein-1 (MCP-1) in renal allografts with chronic renal allograft dysfunction (CRAD), and explore its relationship with interstitial fibrosis and tubular atrophy (IF/TA). METHODS: An immunohistochemical assay and computer-assisted, genuine colored image analysis system were used to detect the expression of RANTES and MCP-1 in renal allografts with CRAD...
July 2016: Transplantation Proceedings
Shun Li, Mengting Ou, Guixue Wang, Liling Tang
Conditionally replicating adenoviruses (CRAds), or known as replication-selective adenoviruses, were discovered as oncolytic gene vectors several years ago. They have a strong ability of scavenging tumor and lesser toxicity to normal tissue. CRAds not only have a tumor-killing ability but also can combine with gene therapy, radiotherapy, and chemotherapy to induce tumor cell apoptosis. In this paper, we review the structure of CRAds and CRAd vectors and summarize the current application of CRAds in tumor detection as well as in radiotherapy and suicide gene-mediating chemotherapy...
October 2016: Applied Microbiology and Biotechnology
Xiangfei Yuan, Qing Zhang, Zhenzhen Li, Xiaolong Zhang, Shiqi Bao, Dongmei Fan, Yongxin Ru, Shuxu Dong, Yizhi Zhang, Yanjun Zhang, Zhou Ye, Dongsheng Xiong
Currently, it is a key challenge to remove the postsurgical residuals and metastasis of hepatocellular carcinoma (HCC). Oncolytic adenoviral virotherapy is an attractive treatment modality for cancer; however, the difficulty remains regarding its intravenous administration. The aim of this study was to develop a targeted therapeutic system which has great potential to overcome the postsurgical residuals and metastasis of HCC. In this system, we developed a conditionally replicative adenovirus (CRAd) loaded on human umbilical cord-derived mesenchymal stem cells (HUMSCs), in which the CRAd contained an adenovirus E1A gene dual regulated by α-fetoprotein promoter and microRNA-122 target sequence...
October 10, 2016: Cancer Letters
Jun-Feng Ye, Yuan-Qiang Lin, Xiu-Hua Yu, Ming-Yuan Liu, Yang Li
The effective antitumor immune responses are dependent on coordinate interaction of various effector cells. Thus, the combination of adoptive immunotherapy and target gene therapy is capable of efficiently generating a productive antitumor immune response. We investigated whether combination of cytokine-induced killer (CIK) cells adoptive immunotherapy and CCL21/IL15 armed oncolytic adenovirus could induce the enhanced antitumor activity. The CCL21/IL15 co-expression oncolytic adenoviruses were constructed by using the AdEasy system, which uses homologous recombination with shuttle plasmids and full length Ad backbones...
September 2016: International Immunopharmacology
Ahmad Mohammad Ashshi, Adel Galal El-Shemi, Igor P Dmitriev, Elena A Kashentseva, David T Curiel
BACKGROUND: A major hurdle incurrent to the human clinical application of conditionally replicative adenovirus (CRAd)-based virotherapy agents is their limited therapeutic efficacy. In this study we evaluated whether arming our previously reported Ad5/3Δ24 CRAd vector containing a 24-base pair deletion in the E1A conserved region 2, which allows selective replication within Rb-p16-deficient tumor cells, to express therapeutic genes could improve oncolytic virus potency in ovarian cancer cells...
June 27, 2016: Journal of Ovarian Research
Zhao-Lun Li, Xuan Liang, He-Cheng Li, Zi-Ming Wang, Tie Chong
AIM: Adenovirus-mediated gene therapy is a novel therapeutic approach for the treatment of cancer, in which replication of the virus itself is the anticancer method. However, the success of this novel therapy is limited due to inefficient delivery of the virus to the target sites. In this study, we used dendritic cells (DCs) as carriers for conditionally replicating adenoviruses (CRAds) in targeting prostate carcinoma (PCa). METHODS: Four types of CRAds, including Ad-PC (without PCa-specific promoter and a recombinant human tumor necrosis factor, rmhTNF, sequence), Ad-PC-rmhTNF (without PCa-specific promoter), Ad-PPC-NCS (without an rmhTNF sequence) and Ad-PPC-rmhTNF, were constructed...
August 2016: Acta Pharmacologica Sinica
Julius Woongki Kim, Brenda Auffinger, Drew A Spencer, Jason Miska, Alan L Chang, Joshua Robert Kane, Jacob S Young, Deepak Kanojia, Jian Qiao, Jill F Mann, Lingjiao Zhang, Meijing Wu, Atique U Ahmed, Karen S Aboody, Theresa V Strong, Charles D Hébert, Maciej S Lesniak
BACKGROUND: CRAd-S-pk7 is a conditionally replicative oncolytic adenoviral vector that contains a survivin promoter and a pk7 fiber modification that confer tumor-specific transcriptional targeting and preferential replication in glioma while sparing the surrounding normal brain parenchyma. METHODS: This IND-enabling study performed under GLP conditions evaluated the toxicity and biodistribution of CRAd-S-pk7 administered as a single intracerebral dose to Syrian hamsters, a permissive model of adenoviral replication...
2016: Journal of Translational Medicine
Yong-Liang Zheng, Si-Si Zhong, Liu-Yan Xin, Yi-Jian Chen
OBJECTIVE: To explore the expression and significance of NLR family, pyrin domain containing 3 (NLRP3), apoptosis associated speck like protein containing a CRAD (ASC) and absent in melanoma 2 (AIM2) of patients with acute leukemia. METHODS: The petipheral blood samples of 19 patients with ALL and 41 patients with ANLL as the AL group (each 20 cases of newly diagnosed, relapsed and complete remission group) and 20 cases of non-hematologic malignancies as the control group were collected from July 2013 to July 2014 in the First Affiliated Hospital of Gannan Medical University...
April 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
Christopher J LaRocca, Joohee Han, Amanda O Salzwedel, Julia Davydova, Mark C Herzberg, Rajaram Gopalakrishnan, Masato Yamamoto
OBJECTIVES: In recent years, the incidence of Human Papilloma Virus (HPV)-positive head and neck squamous cell carcinomas (HNSCC) has markedly increased. Our aim was to design a novel therapeutic agent through the use of conditionally replicative adenoviruses (CRAds) that are targeted to the HPV E6 and E7 oncoproteins. METHODS: Each adenovirus included small deletion(s) in the E1a region of the genome (Δ24 or CB016) intended to allow for selective replication in HPV-positive cells...
May 2016: Oral Oncology
Jie Zhang, Meng Ding, Kai Xu, Lijun Mao, Junian Zheng
The small-interfering RNAs (siRNAs) have been employed to knockdown the expression of cancer-associated genes and shown some promise in cancer therapy. However, synthetic siRNA duplexes or plasmid mediated delivery of siRNAs have several problems, such as short half-life, low transfection efficiency and cytotoxicity associated with transfection. Conditionally replicating adenovirus (CRAds) as the delivery vector for short hairpin RNAs (shRNAs) could overcome these limitations and have shown augmented anti-tumor effects in experimental studies and preclinical trials...
May 17, 2016: Oncotarget
Samuel Ayodele Egieyeh, James Syce, Sarel F Malan, Alan Christoffels
BACKGROUND: A large number of natural products have shown in vitro antiplasmodial activities. Early identification and prioritization of these natural products with potential for novel mechanism of action, desirable pharmacokinetics and likelihood for development into drugs is advantageous. Chemo-informatic profiling of these natural products were conducted and compared to currently registered anti-malarial drugs (CRAD). METHODS: Natural products with in vitro antiplasmodial activities (NAA) were compiled from various sources...
January 29, 2016: Malaria Journal
Samuel Egieyeh, James Syce, Alan Christoffels, Sarel F Malan
In light of current resistance to antimalarial drugs, there is a need to discover new classes of antimalarial agents with unique mechanisms of action. Identification of unique scaffolds from natural products with in vitro antiplasmodial activities may be the starting point for such new classes of antimalarial agents. We therefore conducted scaffold diversity and comparison analysis of natural products with in vitro antiplasmodial activities (NAA), currently registered antimalarial drugs (CRAD) and malaria screen data from Medicine for Malaria Ventures (MMV)...
January 16, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Takashi Kosaka, Julia Davydova, Hidetaka A Ono, Hirotoshi Akiyama, Shu-Ichi Hirai, Shigeo Ohno, Fumitaka Takeshita, Kazunori Aoki, Takahiro Ochiya, Masato Yamamoto, Chikara Kunisaki, Itaru Endo
BACKGROUND: Long-term outcomes of patients with peritoneal dissemination of gastric cancer remain unsatisfactory despite advances in treatment modalities. Internal luminescence conditionally replicative adenovirus (CRAd) presents a novel approach for cancer treatment and imaging. MATERIALS AND METHODS: 3CL is a modified cyclooxygenase-2 (COX2) promoter-driven CRAd which contains the luciferase expression gene for bioluminescence imaging. The visualizing and therapeutic effect of 3CL was evaluated in a mouse model of peritoneal dissemination...
October 2015: Anticancer Research
Guang-Yao Liu, Zhi-Jie Li, Qing-Lin Li, Yan Jin, Yu-Hui Zhu, Yue-Hui Wang, Ming-Yuan Liu, Ya-Gang Li, Yang Li
Conditionally replicating adenoviruses (CRAds) selectively replicate in cancer cells and induce cell lysis, which represents a potential platform for cancer immunotherapy. The chemokine CCL20 exerts antitumor activity via chemoattraction of immature dendritic cells (DCs) and lymphocytes. However, the activation and maturation status of DCs is a limiting factor in the DCs -based immunity response. CD40L induces the phenotypic maturation of DCs, mediates DCs cytokine secretion, and increases the expression of FasL, which mediates apoptosis...
September 2015: International Immunopharmacology
Maria Majernikova, Jaroslav Rosenberger, Lucia Prihodova, Daniele Marcelli, Robert Roland, Johan W Groothoff, Jitse P van Dijk
PURPOSE: Anemia is a predictor of mortality and of self-rated health (SRH). However, studies on the relationship between SRH and changes in hemoglobin (Hb) value over time stratified by chronic kidney disease (CKD) stages are lacking. The aim is to explore whether a change in Hb-value over time associates with SRH at up to 8-year follow-up, stratified for CKD stages. METHODS: A prospective study with a baseline measurement between the 3rd and 12th month after KT was performed on 337 consecutive patients...
January 2016: Quality of Life Research
D Stanley, N Kirby, N Papanikolaou, A Gutierrez
INTRODUCTION: With the implementation of new nonradiographic imaging technologies, system performance characterization is crucial prior to clinical implementation.In this study, the short-term static, spatial reproducibility and temporal drift of the CatalystHD 3-camera nonradiographic imaging system were evaluated. METHODS: Using the CatalystHD Daily Check phantom aligned to the room lasers, both the spatial reproducibility and temporal drift were analyzed in the treatment room with low ambient light (12...
June 2015: Medical Physics
Ilya Ulasov, Anton V Borovjagin, Natalya Kaverina, Brett Schroeder, Nameeta Shah, Biaoyang Lin, Anatoly Baryshnikov, Charles Cobbs
MMP14 (MT1-MMP) is a cell membrane-associated proteinase of the extracellular matrix, whose biological roles vary from angiogenesis to cell proliferation and survival. We recently found a direct correlation between MMP14 expression levels in brain tumors of glioma patients and the disease progression. By using gene silencing as an experimental approach we found that MMP14 knockdown decreases production of pro-angiogenic factors such as VEGF and IL8 and thereby suppresses angiogenesis in glioma tumors. Although the clinical relevance of MMP14 down-regulation and its possible implications for glioma therapy in humans remain unclear, we observed a significant improvement in animal survival upon down-regulation of MMP14 in murine intracranial glioma xenografts infected with MMP14 shRNA-expressing CRAd...
September 1, 2015: Cancer Letters
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