Triptolide Inhibits the AR Signaling Pathway to Suppress the Proliferation of Enzalutamide Resistant Prostate Cancer Cells
In this study, we found that TPL at low dose inhibits the transactivation activity of both full-length and truncated AR without changing their protein levels. Interestingly, TPL inhibits phosphorylation of AR and its CRPC-associated variant AR-V7 at Ser515 through XPB/CDK7. As a result, TPL suppresses the binding of AR to promoter regions in AR target genes along with reduced TFIIH and RNA Pol II recruitment. Moreover, TPL at low dose reduces the viability of prostate cancer cells expressing AR or AR-Vs. Low-dose TPL also shows a synergistic effect with enzalutamide to inhibit CRPC cell survival in vitro, and enhances the ...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Yangyang Han, Weiwei Huang, Jiakuan Liu, Dandan Liu, Yangyan Cui, Ruimin Huang, Jun Yan, Ming Lei Tags: Research Paper Source Type: research

177Lu-Labeled Phosphoramidate-Based PSMA Inhibitors: The Effect of an Albumin Binder on Biodistribution and Therapeutic Efficacy in Prostate Tumor-Bearing Mice
Prostate-specific membrane antigen (PSMA) continues to be an active biomarker for small-molecule PSMA-targeted imaging and therapeutic agents for prostate cancer and various non-prostatic tumors that are characterized by PSMA expression on their neovasculature. One of the challenges for small-molecule PSMA inhibitors with respect to delivering therapeutic payloads is their rapid renal clearance. In order to overcome this pharmacokinetic challenge, we outfitted a 177Lu-labeled phosphoramidate-based PSMA inhibitor (CTT1298) with an albumin-binding motif (CTT1403) and compared its in vivo performance with that of an analogous...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Cindy J. Choy, Xiaoxi Ling, Jonathan J. Geruntho, Sophia K. Beyer, Joseph D. Latoche, Beatrice Langton-Webster, Carolyn J. Anderson, Clifford E. Berkman Tags: Research Paper Source Type: research

Should Low Molecular Weight PSMA Targeted Ligands Get Bigger and Use Albumin Ligands for PSMA Targeting?
Prostate Specific Membrane Antigen (PSMA) is strongly expressed in prostate cancer. Recently a number of low-molecular-weight inhibitors have demonstrated excellent PSMA targeting activity for both imaging as well as Lutecium-177 radiotherapy in human trials. The paper by Choy et al raises the question of whether we can further increase the effectiveness of PSMA targeted therapy by adding an albumin-binding entity to low-molecular-weight agents (Source: Theranostics)
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Steve S. Huang, Warren D.W. Heston Tags: Editorial Source Type: research

Mouse IP-10 Gene Delivered by Folate-modified Chitosan Nanoparticles and Dendritic/tumor Cells Fusion Vaccine Effectively Inhibit the Growth of Hepatocellular Carcinoma in Mice
In this study, we used nanoparticles of folate (FA)-modified chitosan, a non-viral vector capable of targeting tumor cells with high expression of FA receptors. FA-chitosan nanoparticles were used as biological carriers for the expression plasmid of the mouse interferon-induced protein-10 (mIP-10) gene, a potent chemoattractant for cytotoxic T cells. The combination of FA-chitosan/mIP-10 and DC/tumor cell fusion vaccine against hepatocellular carcinoma (HCC) effectively inhibited the growth of implanted HCC tumors and prolonged the survival of mice. The combination therapy significantly reduced myeloid-derived suppressor c...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Zixi Hu, Jiaojiao Chen, Sufang Zhou, Nuo Yang, Siliang Duan, Zhenghua Zhang, Jing Su, Jian He, Zhiyong Zhang, Xiaoling Lu, Yongxiang Zhao Tags: Research Paper Source Type: research

Neonatal Heart-Enriched miR-708 Promotes Proliferation and Stress Resistance of Cardiomyocytes in Rodents
In this study, a subset of miRNAs including miR-708 were identified to be much more abundant in the embryonic and neonatal cardiomyocytes than that in adult rodents. Overexpression of miR-708 promoted cellular proliferation of H9C2 cells or primary cardiomyocytes from neonatal rats or mice in vitro. Lipid nanoparticle delivery of miR-708 promoted myocardial regeneration and heart function recovery in vivo. In addition, miR-708 protected cardiomyocytes against stress-induced apoptosis under hypoxia or isoproterenol treatments. miR-708 inhibited the expression of MAPK14, which has been demonstrated arresting the cell cycle i...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Shengqiong Deng, Qian Zhao, Lixiao Zhen, Chuyi Zhang, Cuicui Liu, Guangxue Wang, Lin Zhang, Luer Bao, Ying Lu, Lingyu Meng, Jinhui L ü , Ping Yu, Xin Lin, Yuzhen Zhang, Yi-Han Chen, Huimin Fan, William C. Cho, Zhongmin Liu, Zuoren Yu Tags: Research Paper Source Type: research

Implantable and Biodegradable Macroporous Iron Oxide Frameworks for Efficient Regeneration and Repair of Infracted Heart
The construction, characterization and surgical application of a multilayered iron oxide-based macroporous composite framework were reported in this study. The framework consisted of a highly porous iron oxide core, a gelatin-based hydrogel intermediary layer and a matrigel outer cover, which conferred a multitude of desirable properties including excellent biocompatibility, improved mechanical strength and controlled biodegradability. The large pore sizes and high extent of pore interconnectivity of the framework stimulated robust neovascularization and resulted in substantially better cell viability and proliferation as ...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Wenshuo Wang, Hongyue Tao, Yun Zhao, Xiaotian Sun, Jing Tang, Cordelia Selomulya, Jia Tang, Tianchan Chen, Yang Wang, Minglei Shu, Lei Wei, Guanyu Yi, Jixue Zhou, Lai Wei, Chunsheng Wang, Biao Kong Tags: Research Paper Source Type: research

Thermoacoustic Imaging and Therapy Guidance based on Ultra-short Pulsed Microwave Pumped Thermoelastic Effect Induced with Superparamagnetic Iron Oxide Nanoparticles
In this study, human serum albumin (HSA)-functionalized superparamagnetic iron oxide nanoparticle (HSA-SPIO) is used as a multifunctional nanoprobe with clinical application potential for MRI, TA imaging and treatment of tumor. In addition to be a MRI contrast agent for tumor localization, HSA-SPIO can absorb pulsed microwave energy and transform it into shockwave via the thermoelastic effect. Thereby, the reconstructed TA image by detecting TA signal is expected to be a sensitive and accurate representation of the HSA-SPIO accumulation in tumor. More importantly, owing to the selective retention of HSA-SPIO in tumor tissu...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Liewei Wen, Sihua Yang, Junping Zhong, Quan Zhou, Da Xing Tags: Research Paper Source Type: research

Surface De-PEGylation Controls Nanoparticle-Mediated siRNA Delivery In Vitro and In Vivo
The present work proposes a unique de-PEGylation strategy for controllable delivery of small interfering RNA (siRNA) using a robust lipid-polymer hybrid nanoparticle (NP) platform. The self-assembled hybrid NPs are composed of a lipid-poly(ethylene glycol) (lipid-PEG) shell and a polymer/cationic lipid solid core, wherein the lipid-PEG molecules can gradually dissociate from NP surface in the presence of serum albumin. The de-PEGylation kinetics of a series of different lipid-PEGs is measured with their respective NPs, and the NP performance is comprehensively investigated in vitro and in vivo. This systematic study reveal...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Xi Zhu, Wei Tao, Danny Liu, Jun Wu, Zilei Guo, Xiaoyuan Ji, Zameer Bharwani, Lili Zhao, Xiaoping Zhao, Omid C. Farokhzad, Jinjun Shi Tags: Research Paper Source Type: research

Drug-Bearing Supramolecular Filament Hydrogels as Anti-Inflammatory Agents
We report here on the covalent conversion of the anti-inflammatory agent ketoprofen into self-assembling prodrugs that enable the effective purification of ketoprofen enantiomers, the improved selectivity and potency of ketoprofen, as well as the formation of one-component drug-bearing supramolecular hydrogels. We found that the ketoprofen hydrogelator could exhibit much-enhanced selectivity for cyclooxygenase 2 (COX-2) over COX-1, reduce the concentration of inflammatory cytokines (IL-1 and TNFα), and induce apoptosis in fibroblast-like synoviocytes while maintaining biocompatibility with healthy chondrocytes. In ad...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Zhipeng Chen, Lei Xing, Qin Fan, Andrew G. Cheetham, Ran Lin, Barbara Holt, Liwen Chen, Yanyu Xiao, Honggang Cui Tags: Research Paper Source Type: research

Melatonin Suppresses Neuropathic Pain via MT2-Dependent and -Independent Pathways in Dorsal Root Ganglia Neurons of Mice
In conclusion, only MT2 was expressed in the DRG neurons and up-regulated upon cuff implantation. The analgesic effects of Mel in cuff-implanted mice were closely associated with both MT2-dependent (MAPK-calcium channels) and MT2-independent (NOS1) pathways in the DRG. (Source: Theranostics)
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Jia-Ji Lin, Ye Lin, Tian-Zhi Zhao, Chun-Kui Zhang, Ting Zhang, Xiao-Li Chen, Jia-Qi Ding, Ting Chang, Zhuo Zhang, Chao Sun, Dai-Di Zhao, Jun-Lin Zhu, Zhu-Yi Li, Jin-Lian Li Tags: Research Paper Source Type: research

Parkin Knockout Inhibits Neuronal Development via Regulation of Proteasomal Degradation of p21
PARK2 encodes for the E3 ubiquitin ligase parkin and is implicated in the development of Parkinson's disease (PD). Although the neuroprotective role of parkin is well known, the mechanism of PARK2's function in neural stem differentiation has not yet been thoroughly studied. Co-expressions network analysis showed that synaptosomal-associated protein 25 (SNAP-25) and brain-derived neurotrophic factor (BDNF) were positively correlated with parkin, but negatively correlated with p21 in human patient brain. We investigated a link between the ubiquitin E3 ligase parkin and proteasomal degradation of p21 for the control of neura...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Mi Hee Park, Hwa-Jeong Lee, Hye Lim Lee, Dong Ju Son, Jung Hoon Ju, Byung Kook Hyun, Sung Hee Jung, Ju-Kyoung Song, Dong Hun Lee, Chul Ju Hwang, Sang Bae Han, Sanghyeon Kim, Jin Tae Hong Tags: Research Paper Source Type: research

PSMA-PET for Lymph Node Detection in Recurrent Prostate Cancer: How do we use the Magic Bullet?
(Source: Theranostics)
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Tobias Maurer, Declan G. Murphy, Michael S. Hofman, Matthias Eiber Tags: Editorial Source Type: research

PET Tracer 18F-Fluciclovine Can Detect Histologically Proven Bone Metastatic Lesions: A Preclinical Study in Rat Osteolytic and Osteoblastic Bone Metastasis Models
Conclusion: These results suggest that fluciclovine-PET can visualize true osteolytic and osteoblastic bone metastatic lesions. (Source: Theranostics)
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Shuntaro Oka, Masaru Kanagawa, Yoshihiro Doi, David M. Schuster, Mark M. Goodman, Hirokatsu Yoshimura Tags: Research Paper Source Type: research

In Molecular Pursuit of Bone Metastasis by Fluciclovine PET
Diagnosing bone metastases with traditional anatomic modalities, such as MRI and CT, is limited by sensitivity, and conventional bone radiotracers are only indirect markers of cancer activity. Fortunately, molecular imaging is uniquely capable of providing radiotracers such as fluciclovine and radiolabeled choline, that actually target tumors in the bone. The merits of research in imaging osseous metastases in animal models using these radiotracers and the implications for future clinical translation are discussed. (Source: Theranostics)
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Liza Lindenberg Tags: Editorial Source Type: research

Current Strategies and Challenges for Purification of Cardiomyocytes Derived from Human Pluripotent Stem Cells
Cardiomyocytes (CMs) derived from human pluripotent stem cells (hPSCs) are considered a most promising option for cell-based cardiac repair. Hence, various protocols have been developed for differentiating hPSCs into CMs. Despite remarkable improvement in the generation of hPSC-CMs, without purification, these protocols can only generate mixed cell populations including undifferentiated hPSCs or non-CMs, which may elicit adverse outcomes. Therefore, one of the major challenges for clinical use of hPSC-CMs is the development of efficient isolation techniques that allow enrichment of hPSC-CMs. In this review, we will discuss...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Kiwon Ban, Seongho Bae, Young-sup Yoon Tags: Review Source Type: research

Metabolomics Identifies Metabolic Markers of Maturation in Human Pluripotent Stem Cell-Derived Cardiomyocytes
In this study we identified global metabolic changes which take place during long-term culture and maturation of hPSC-CMs derived from three different hPSC lines. We have identified several metabolic pathways, including phospholipid metabolism and pantothenate and Coenzyme A metabolism, which showed significant enrichment upon maturation in addition to fatty acid oxidation and metabolism. We also identified increases in glycerophosphocholine and the glycerophosphocholine:phosphocholine ratio as potential metabolic biomarkers of maturation. These biomarkers were also affected in a similar manner during murine heart developm...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Vijesh J. Bhute, Xiaoping Bao, Kaitlin K. Dunn, Kylie R. Knutson, Eric C. McCurry, Gyuhyung Jin, Wei-Hua Lee, Sarah Lewis, Akihiro Ikeda, Sean P. Palecek Tags: Research Paper Source Type: research

c-Myc is Required for BRAFV600E-Induced Epigenetic Silencing by H3K27me3 in Tumorigenesis
BRAFV600E mutation is frequently found in human cancers particularly thyroid cancer and melanoma, and is involved in the regulation of gene expression through activating MAPK/Erk signaling. Trimethylation of histone 3 lysine 27 (H3K27me3) is a critical epigenetic mark for the maintenance of gene silencing in tumorigenesis. However, molecular mechanism underlying the complex interplay between these two molecular events remains to be explored. In the present study, we conducted chromatin immunoprecipitation combined with next-generation sequencing (ChIP-Seq) and expression microarray analysis in NIH3T3 cells to explore the r...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Yiping Qu, Qi Yang, Juan Liu, Bingyin Shi, Meiju Ji, Gang Li, Peng Hou Tags: Research Paper Source Type: research

A Look Inside of the Complex Pathogenesis of B-RAF(V600E)-Driven Cancer
Cancer is a very complex disease, where cell alterations (i.e. gene mutations, dysregulated signaling pathway(s) and epigenetic modifications) contribute to its development and progression. Elucidating the connections among these cell modifications is a critical challenge, in order to understand the mechanisms which are activated from cancer cells to survive and proliferate. Interesting, Prof. Peng Hou and colleagues, at the First Affiliated Hospital of Xi'an Jiaotong University in China, identified unknown epigenetic mechanisms and their involvement in the tumorigenesis of B-RAF(V600E)-driven cancer. (Source: Theranostics)
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Emilia Caputo Tags: Editorial Source Type: research

Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine
Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Martin Pool, H. Rudolf de Boer, Marjolijn N. Lub-de Hooge, Marcel A.T.M. van Vugt, Elisabeth G.E. de Vries Tags: Review Source Type: research

Suppression Of β -catenin Nuclear Translocation By CGP57380 Decelerates Poor Progression And Potentiates Radiation-Induced Apoptosis in Nasopharyngeal Carcinoma
In this study, we showed that β-catenin signaling (including β-catenin, cyclin D1, c-Myc, and MMP-7) and p-eIF4E expression were elevated in nasopharyngeal carcinoma (NPC) compared with non-cancerous nasopharyngeal epithelial tissues, and was associated with clinical characteristics of NPC patients. Lymph node metastasis, gender, aberrant β-catenin expression, and elevated levels of MMP-7 and cyclin D1 were independent prognostic factors. Significantly, expression of p-eIF4E was positively correlated with β-catenin, and targeting the MNK-eIF4E axis with CGP57380 downregulated β-catenin in the nucle...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Weiyuan Wang, Qiuyuan Wen, Jiadi Luo, Shuzhou Chu, Lingjiao Chen, Lina Xu, Hongjing Zang, Mohannad Ma Alnemah, Jinghe Li, Jianhua Zhou, Songqing Fan Tags: Research Paper Source Type: research

Epigenomic and Functional Characterization of Junctophilin 3 (JPH3) as a Novel Tumor Suppressor Being Frequently Inactivated by Promoter CpG Methylation in Digestive Cancers
Junctophilin (JPH) proteins stabilize junctional membrane complexes between plasma membrane and endoplasmic reticulum, also implicated in some human diseases. JPH3 mutations are linked to Huntington's disease-like 2 syndrome. Through epigenomic study of a colon cancer cell line pair (HCT116 and DKO), we identified JPH3 as a methylated novel tumor suppressor gene (TSG) candidate at 16q24. We further studied its epigenetic alterations and functions in digestive tumorigenesis. JPH3 expression at the RNA level was found to be frequently silenced or reduced in colorectal and gastric cancers due to its promoter CpG methylation, ...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Xiaotong Hu, Yeye Kuang, Lili Li, Haimei Tang, Qinglan Shi, Xingsheng Shu, Yanjiao Zhang, Francis KL Chan, Qian Tao, Chao He Tags: Research Paper Source Type: research

Vandetanib-eluting Radiopaque Beads: In vivo Pharmacokinetics, Safety and Toxicity Evaluation following Swine Liver Embolization
CONCLUSIONS: Hepatic intra-arterial administration of VERB results in a low systemic exposure and enables sustained delivery of VTB to target tissues following embolization. Changes in the liver tissue are consistent with an effective embolization and this study has demonstrated that VERB100 is well tolerated with no obvious systemic toxicity. (Source: Theranostics)
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Alban Denys, Peter Czuczman, David Grey, Zainab Bascal, Rhys Whomsley, Hugh Kilpatrick, Andrew L. Lewis Tags: Research Paper Source Type: research

Self-Assembly of Semiconducting-Plasmonic Gold Nanoparticles with Enhanced Optical Property for Photoacoustic Imaging and Photothermal Therapy
Although various noble metal and semiconducting molecules have been developed as photoacoustic (PA) agents, the use of semiconducting polymer-metal nanoparticle hybrid materials to enhance PA signal has not been explored. A novel semiconducting-plasmonic nanovesicle was fabricated by self-assembly of semiconducting poly(perylene diimide) (PPDI) and poly(ethylene glycol (PEG) tethered gold nanoparticles (Au@PPDI/PEG). A highly localized and strongly enhanced electromagnetic (EM) field is distributed between adjacent gold nanoparticles in the vesicular shell, where the absorbing collapsed PPDI is present. Significantly, the ...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Zhen Yang, Jibin Song, Yunlu Dai, Jingyi Chen, Feng Wang, Lisen Lin, Yijing Liu, Fuwu Zhang, Guocan Yu, Zijian Zhou, Wenpei Fan, Wei Huang, Quli Fan, Xiaoyuan Chen Tags: Research Paper Source Type: research

Interleukin-32 α Inhibits Endothelial Inflammation, Vascular Smooth Muscle Cell Activation, and Atherosclerosis by Upregulating Timp3 and Reck through suppressing microRNA-205 Biogenesis
Conclusion: Our findings provide the first direct evidence that IL-32α is an anti-inflammatory and anti-atherogenic cytokine that may be useful as a diagnostic and therapeutic protein in atherosclerosis. (Source: Theranostics)
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Dong Ju Son, Yu Yeon Jung, Young Sik Seo, Heonyong Park, Dong Hun Lee, Sanghyeon Kim, Yoon-Seok Roh, Sang Bae Han, Do Young Yoon, Jin Tae Hong Tags: Research Paper Source Type: research

E-selectin-targeted Sialic Acid-PEG-dexamethasone Micelles for Enhanced Anti-Inflammatory Efficacy for Acute Kidney Injury
The effective treatment for acute kidney injury (AKI) is currently limited, and care is primarily supportive. Sialic acid (SA) is main component of Sialyl Lewisx antigen on the mammalian cell surface, which participates in E-selectin binding. Therefore, dexamethasone(DXM)-loaded E-selectin-targeting sialic acid-polyethylene glycol-dexamethasone (SA-PEG-DXM/DXM) conjugate micelles are designed for ameliorating AKI. The conjugates are synthesized via the esterification reaction between PEG and SA or DXM, and can spontaneously form micelles in an aqueous solution with a 65.6 µg/mL critical micelle concentration. Free DX...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Jing-Bo Hu, Xu-Qi Kang, Jing Liang, Xiao-Juan Wang, Xiao-Ling Xu, Ping Yang, Xiao-Ying Ying, Sai-Ping Jiang, Yong-Zhong Du Tags: Research Paper Source Type: research

A Paper-Based Device for Performing Loop-Mediated Isothermal Amplification with Real-Time Simultaneous Detection of Multiple DNA Targets
Paper-based diagnostic devices have many advantages as a one of the multiple diagnostic test platforms for point-of-care (POC) testing because they have simplicity, portability, and cost-effectiveness. However, despite high sensitivity and specificity of nucleic acid testing (NAT), the development of NAT based on a paper platform has not progressed as much as the others because various specific conditions for nucleic acid amplification reactions such as pH, buffer components, and temperature, inhibitions from technical differences of paper-based device. Here, we propose a paper-based device for performing loop-mediated iso...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Youngung Seok, Hyou-Arm Joung, Ju-Young Byun, Hyo-Sung Jeon, Su Jeong Shin, Sanghyo Kim, Young-Beom Shin, Hyung Soo Han, Min-Gon Kim Tags: Research Paper Source Type: research

Down-regulated miR-23a Contributes to the Metastasis of Cutaneous Melanoma by Promoting Autophagy
Melanoma is among the most aggressive tumors, and the occurrence of metastasis leads to a precipitous drop in the patients' survival. Therefore, identification of metastasis-associated biomarkers and therapeutic targets will contribute a lot to improving melanoma theranostics. Recently, microRNAs (miRNAs) have been implicated in modulating cancer invasion and metastasis, and are proved as potential non-invasive biomarkers in sera for various tumors. Here, we reported miR-23a as a novel metastasis-associated miRNA that played a remarkable role in modulating melanoma invasive and metastatic capacity and was of great value in...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Weinan Guo, Huina Wang, Yuqi Yang, Sen Guo, Weigang Zhang, Yu Liu, Xiuli Yi, Jingjing Ma, Tao Zhao, Lin Liu, Zhe Jian, Ling Liu, Gang Wang, Tianwen Gao, Qiong Shi, Chunying Li Tags: Research Paper Source Type: research

Modulation of Salmonella Tumor-Colonization and Intratumoral Anti-angiogenesis by Triptolide and Its Mechanism
In this study, we investigated whether an anti-inflammation and antiangiogenesis compound triptolide could improve the efficacy of VNP20009, a highly attenuated Salmonella strain, against mice melanoma. By comparing the effects of conventional VNP20009 monotherapy and a combination therapy that uses both triptolide and VNP20009, we found that triptolide significantly improved the tumour colonization of VNP20009 by reducing the number of infiltrated neutrophils in the melanoma, which led to a larger necrotic area in the melanoma. Moreover, the combination therapy suppressed tumour angiogenesis by reducing the expression of ...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Jianxiang Chen, Yiting Qiao, Bo Tang, Guo Chen, Xiufeng Liu, Bingya Yang, Jing Wei, Xiangyu Zhang, Xiawei Cheng, Pan Du, Wenhui Jiang, Qingang Hu, Zi-Chun Hua Tags: Research Paper Source Type: research

Targeted Delivery to Tumor-associated Pericytes via an Affibody with High Affinity for PDGFR β Enhances the in vivo Antitumor Effects of Human TRAIL
Human tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL) has exhibited superior in vitro cytotoxicity in a variety of tumor cells. However, hTRAIL showed a disappointing anticancer effect in clinical trials, although hTRAIL-based regimens were well tolerated. One important reason might be that hTRAIL was largely trapped by its decoy receptors, which are ubiquitously expressed on normal cells. Tumor-targeted delivery might improve the tumor uptake and thus enhance the antitumor effect of hTRAIL. Platelet-derived growth factor receptor β (PDGFRβ)-expressing pericytes are enriched in tumor tissues deri...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Ze Tao, Hao Yang, Qiuxiao Shi, Qing Fan, Lin Wan, Xiaofeng Lu Tags: Research Paper Source Type: research

Boosting the Peroxidase-Like Activity of Nanostructured Nickel by Inducing Its 3+ Oxidation State in LaNiO3 Perovskite and Its Application for Biomedical Assays
Catalytic nanomaterials with intrinsic enzyme-like activities, called nanozymes, have recently attracted significant research interest due to their unique advantages relative to natural enzymes and conventional artificial enzymes. Among the nanozymes developed, particular interests have been devoted to nanozymes with peroxidase mimicking activities because of their promising applications in biosensing, bioimaging, biomedicine, etc. Till now, lots of functional nanomaterials have been used to mimic peroxidase. However, few studies have focused on the Ni-based nanomaterials for peroxidase mimics. In this work, we obtained th...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Xiaoyu Wang, Wen Cao, Li Qin, Tingsheng Lin, Wei Chen, Shichao Lin, Jia Yao, Xiaozhi Zhao, Min Zhou, Cheng Hang, Hui Wei Tags: Research Paper Source Type: research

Modulating microRNAs as Novel Therapeutic Targets in Cardiac Fibrosis
This commentary highlights the findings by Tao et al. (Theranostics 2016; 6: 2068-2083) that targeting miR-433 may be a potential therapeutic strategy for myocardial fibrosis and subsequently discusses the obstacles and prospects associated with the application of therapeutic microRNAs in anti-fibrosis treatment. (Source: Theranostics)
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Zhongxiu Chen, Yajiao Li, Ke Dian, Li Rao Tags: Commentary Source Type: research

NPM1 Mutant Mediated PML Delocalization and Stabilization Enhances Autophagy and Cell Survival in Leukemic Cells
In this study, we showed that mutant NPM1 elevated autophagic activity and autophagic activation contributed to leukemic cell survival in vitro. Meanwhile, we also found high expression of promyelocytic leukemia gene (PML) and its cytoplasmic dislocation in primary NPM1-mutated AML blasts and NPM1-mA positive OCI-AML3 cells. Mechanically, mutant NPM1 interacted with PML and mediated it delocalization as well as stabilization. Notably, NPM1-mA knockdown impaired autophagic activity, while induced expression of PML reversed this effect. Finally, we confirmed that PML modulated autophagic activity via AKT signal. These findin...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Qin Zou, Shi Tan, Zailin Yang, Qian Zhan, Hongjun Jin, Jingrong Xian, Shuaishuai Zhang, Liyuan Yang, Lu Wang, Ling Zhang Tags: Research Paper Source Type: research

A Fluorogenic Probe for Ultrafast and Reversible Detection of Formaldehyde in Neurovascular Tissues
Formaldehyde (FA) is endogenously produced in live systems and has been implicated in a diverse array of pathophysiological processes. To disentangle the detailed molecular mechanisms of FA biology, a reliable method for monitoring FA changes in live cells would be indispensable. Although there have been several fluorescent probes reported to detect FA, most are limited by the slow detection kinetics and the intrinsic disadvantage of detecting FA in an irreversible manner which may disturb endogenous FA homeostasis. Herein we developed a coumarin-hydrazonate based fluorogenic probe (PFM) based on a finely-tailored stereoel...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Xing-Guang Liang, Bo Chen, Ling-Xiao Shao, Juan Cheng, Ming-Zhu Huang, Yu Chen, Yong-Zhou Hu, Yi-Feng Han, Feng Han, Xin Li Tags: Research Paper Source Type: research

Concurrent Chemoradiotherapy with or without Anti-EGFR-Targeted Treatment for Stage II-IVb Nasopharyngeal Carcinoma: Retrospective Analysis with a Large Cohort and Long Follow-up
We examined the benefits of the combination of anti-EGFR targeted treatment, cetuximab (CTX) or nimotuzumab (NTZ) and concurrent platinum-based chemoradiotherapy (CCRT) compared with CCRT alone in patients with stage II - IVb nasopharyngeal carcinoma (NPC). A total of 1,628 eligible patients with stage II - IVb NPC, who received CCRT (three cycles of 100 mg/m2 cisplatin every 3 weeks with intensity-modulated radiotherapy) with or without CTX or NTZ between June 2009 and December 2013 were included in the analysis. Using propensity scores to adjust for potential prognostic factors, a well-balanced cohort of 878 patients was...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Rui You, Yi-Jun Hua, You-Ping Liu, Qi Yang, Yi-Nuan Zhang, Ji-Bin Li, Chao-Feng Li, Xiong Zou, Tao Yu, Jing-Yu Cao, Meng-Xia Zhang, Rou Jiang, Rui Sun, Hao-Yuan Mo, Ling Guo, Ka-Jia Cao, Ai-Hua Lin, Ying Sun, Chao-Nan Qian, Jun Ma, Ming-Yuan Chen Tags: Research Paper Source Type: research

Atg9b Deficiency Suppresses Autophagy and Potentiates Endoplasmic Reticulum Stress-Associated Hepatocyte Apoptosis in Hepatocarcinogenesis
The aim of this study was to investigate the mechanism underlying autophagy deficiency during hepatic carcinogenesis. For this purpose, we used choline-deficient, amino acid-defined (CDAA) hepatocarcinogenesis model in mice. miRNA microarrays combined with computational target predictions and GO analysis were used to identify molecular processes involved in carcinogenesis. PCR profiler array was employed to detect the dysregulated autophagy-related genes during carcinogenesis. We observed induction of hepatic tumours with increased inflammation, DNA damage, and cell death. These cellular processes were particularly detecte...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Ning Wang, Hor-Yue Tan, Sha Li, Yibin Feng Tags: Research Paper Source Type: research

YD277 Suppresses Triple-Negative Breast Cancer Partially Through Activating the Endoplasmic Reticulum Stress Pathway
In this study, we demonstrated that YD277 significantly induced G1 cell cycle arrest and apoptosis in MDA-MB-231 and MDA-MB-468 TNBC cells, independent of KLF5 inhibition. YD277 also reduced the protein expression levels of Cyclin D1, Bcl2 and Bclxl and promoted the expression of p21 and p27. Moreover, the pro-apoptotic activity of YD277 in TNBC was mediated by the transcription of IRE1α, a key molecule in the endoplasmic reticulum (ER) stress pathway. Finally, YD277 (15 mg/kg) significantly suppressed the growth of MDA-MB-231 tumor xenografts in nude mice. These findings indicate that YD277 is a promising chemothera...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Zekun Chen, Qiuju Wu, Ye Ding, Wenhui Zhou, Rong Liu, Haiying Chen, Jia Zhou, Jing Feng, Ceshi Chen Tags: Research Paper Source Type: research

[177Lu]pentixather: Comprehensive Preclinical Characterization of a First CXCR4-directed Endoradiotherapeutic Agent
Conclusions: [177Lu]pentixather shows excellent in vivo CXCR4-targeting characteristics and a suitable pharmacokinetic profile, leading to high tumor uptake and retention and thus high radiation doses to tumor tissue during PRRT, suggesting high clinical potential of this [68Ga]pentixafor/[177Lu]pentixather based CXCR4-targeted theranostic concept. (Source: Theranostics)
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Margret Schottelius, Theresa Osl, Andreas Poschenrieder, Frauke Hoffmann, Seval Beykan, Heribert H ä nscheid, Andreas Schirbel, Andreas K. Buck, Saskia Kropf, Markus Schwaiger, Ulrich Keller, Michael Lassmann, Hans-J ü rgen Wester Tags: Research Paper Source Type: research

Quantification of Tumor Vascular Permeability and Blood Volume by Positron Emission Tomography
Conclusions: We successfully developed a relatively convenient and novel strategy to evaluate vascular permeability and blood volume using NEB PET. This method will be advantageous in evaluating vascular permeability, promoting drug delivery, and monitoring tumor response to therapeutics that affect tumor angiogenesis. (Source: Theranostics)
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Haojun Chen, Xiao Tong, Lixin Lang, Orit Jacobson, Bryant C. Yung, Xiangyu Yang, Ruiliang Bai, Dale O. Kiesewetter, Ying Ma, Hua Wu, Gang Niu, Xiaoyuan Chen Tags: Research Paper Source Type: research

An [18F]-Positron-Emitting, Fluorescent, Cerebrospinal Fluid Probe for Imaging Damage to the Brain and Spine
Fluorescein is modified to bear 18F so that it can act as both a positron emitter, and a fluorophore, allowing detection by positron emission tomography (PET), scintillation, and fluorescent imaging (FL). [18F]-2 is injected into the intrathecal space of rats and used to observe the cerebrospinal fluid (CSF) that bathes the brain and spine. Injury in three different applications is visualized with [18F]-2: 1) detection of a 0.7 mm paranasal-sinus CSF leak (CSFL); 2) detection of 0.5 mm puncture damage to the thoracic spine (acute spinal cord injury); and 3) detection of intracerebral hemorrhage/edema because of traumatic b...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Harikrishna Kommidi, Hua Guo, Nandi Chen, Dohyun Kim, Bin He, Amy P. Wu, Omer Aras, Richard Ting Tags: Research Paper Source Type: research

Visualization of Tumor-Immune Interaction - Target-Specific Imaging of S100A8/A9 Reveals Pre-Metastatic Niche Establishment
We report the application of antibody-based single-photon emission computed tomography (SPECT) for detection of S100A8/A9 in vivo as an imaging marker for pre-metastatic tissue priming.Methods A syngeneic model system for invasive breast cancer with (4T1.2) or without (67NR) the tendency to form lung metastasis was established in BALB/c mice. A SPECT-probe has been generated and tested for visualization of S100A9 release. Tumor-associated changes in numbers and fuction of immune cells in pre-metastatic tissue were evaluated by flow cytometry and confocal microscopy.Results S100A8/A9 imaging reflected MDSC abundance and the...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Michel Eisenblaetter, Fabian Flores-Borja, Jae Jin Lee, Christina Wefers, Hannah Smith, Rebekka Hueting, Margaret S Cooper, Philip J Blower, Dominic Patel, Manuel Rodriguez-Justo, Hanna Milewicz, Thomas Vogl, Johannes Roth, Andrew Tutt, Tobias Schaeffter, Tags: Research Paper Source Type: research

In-depth Characterization of a TCR-specific Tracer for Sensitive Detection of Tumor-directed Transgenic T Cells by Immuno-PET
A number of different technologies have been developed to monitor in vivo the distribution of gene-modified T cells used in immunotherapy. Nevertheless, in-depth characterization of novel approaches with respect to sensitivity and clinical applicability are so far missing. We have previously described a novel method to track engineered human T cells in tumors using 89Zr-Df-aTCRmu-F(ab')2 targeting the murinized part of the TCR beta domain (TCRmu) of a transgenic TCR. Here, we performed an in-depth in vitro characterization of the tracer in terms of antigen affinity, immunoreactivity, influence on T-cell functionality and s...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Nahid Yusufi, Sabine Mall, Henrique de Oliveira Bianchi, Katja Steiger, Sybille Reder, Richard Klar, Stefan Audehm, Mona Mustafa, Stephan Nekolla, Christian Peschel, Markus Schwaiger, Angela M Krackhardt, Calogero D`Alessandria Tags: Research Paper Source Type: research

Vibrational Profiling of Brain Tumors and Cells
This study reports vibration profiles of neuronal cells and tissues as well as brain tumor and neocortical specimens. A contact-free method and analysis protocol was designed to convert an atomic force microscope into an ultra-sensitive microphone with capacity to record and listen to live biological samples. A frequency of 3.4 Hz was observed for both cultured rat hippocampal neurons and tissues and vibration could be modulated pharmacologically. Malignant astrocytoma tissue samples obtained from operating room, transported in artificial cerebrospinal fluid, and tested within an hour, vibrated with a much different freque...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Sultan L Nelson, Dustin T Proctor, Ahmad Ghasemloonia, Sanju Lama, Kourosh Zareinia, Younghee Ahn, Mustafa R Al-Saiedy, Francis HY Green, Matthias W Amrein, Garnette R Sutherland Tags: Research Paper Source Type: research

3-D Electrochemical Impedance Spectroscopy Mapping of Arteries to Detect Metabolically Active but Angiographically Invisible Atherosclerotic Lesions
We designed a novel 6-point electrochemical impedance spectroscopy (EIS) sensor with 15 combinations of permutations for the 3-D mapping and detection of metabolically active atherosclerotic lesions. Two rows of 3 stretchable electrodes circumferentially separated by 120° were mounted on an inflatable balloon for intravascular deployment and endoluminal interrogation. The configuration and 15 permutations of 2-point EIS electrodes allowed for deep arterial penetration via alternating current (AC) to detect varying degrees of lipid burden with distinct impedance profiles (Ω). By virtue of the distinctive impedimet...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Ren é R. Sevag Packard, Yuan Luo, Parinaz Abiri, Nelson Jen, Olcay Aksoy, William M. Suh, Yu-Chong Tai, Tzung K. Hsiai Tags: Research Paper Source Type: research

Gut Microbiota-Mediated Personalized Treatment of Hyperlipidemia Using Berberine
Nitroreductases (NRs) are bacterial enzymes that reduce nitro-containing compounds. We have previously reported that NR of intestinal bacteria is a key factor promoting berberine (BBR) intestinal absorption. We show here that feeding hamsters with high fat diet (HFD) caused an increase in blood lipids and NR activity in the intestine. The elevation of fecal NR by HFD was due to the increase in either the fraction of NR-producing bacteria or their activity in the intestine. When given orally, BBR bioavailability in the HFD-fed hamsters was higher than that in those fed with normal chow (by +72%, *P
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Yan Wang, Qian Tong, Jia-Wen Shou, Zhen-Xiong Zhao, Xiao-Yang Li, Xian-Feng Zhang, Shu-Rong Ma, Chi-Yu He, Yuan Lin, Bao-Ying Wen, Fang Guo, Jie Fu, Jian-Dong Jiang Tags: Research Paper Source Type: research

miR-196a Enhances Neuronal Morphology through Suppressing RANBP10 to Provide Neuroprotection in Huntington's Disease
MicroRNAs (miRNAs) play important roles in several neurobiological processes, including the development and progression of diseases. Previously, we identified that one specific miRNA, miR-196a, provides neuroprotective effects on Huntington's disease (HD), although the detailed mechanism is still unclear. Based on our bioinformatic analyses, we hypothesize miR-196a might offer neuroprotective functions through improving cytoskeletons of brain cells. Here, we show that miR-196a could enhance neuronal morphology, further ameliorating intracellular transport, synaptic plasticity, neuronal activity, and learning and memory abi...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Lu-Shiun Her, Su-Han Mao, Chih-Yi Chang, Pei-Hsun Cheng, Yu-Fan Chang, Han-In Yang, Chuan-Mu Chen, Shang-Hsun Yang Tags: Research Paper Source Type: research

Ultrasonographic Imaging and Anti-inflammatory Therapy of Muscle and Tendon Injuries Using Polymer Nanoparticles
Ultrasonography is a reliable diagnostic modality for muscle and tendon injuries, but it has been challenging to find right diagnosis of minor musculoskeletal injuries by conventional ultrasonographic imaging. A large amount of hydrogen peroxide (H2O2) are known to be generated during tissue damages such as mechanical injury and therefore H2O2 holds great potential as a diagnostic and therapeutic marker for mechanical injuries in the musculoskeletal system. We previously developed poly(vanillyl alcohol-co-oxalate) (PVAX), which rapidly scavenges H2O2 and exerts antioxidant and anti-inflammatory activity in H2O2-associated ...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Gi-Wook Kim, Changsun Kang, Young-Bin Oh, Myoung-Hwan Ko, Jeong-Hwan Seo, Dongwon Lee Tags: Research Paper Source Type: research

PSMA-Targeted Theranostic Nanocarrier for Prostate Cancer
Herein, we report the use of a theranostic nanocarrier (Folate-HBPE(CT20p)) to deliver a therapeutic peptide to prostate cancer tumors that express PSMA (folate hydrolase 1). The therapeutic peptide (CT20p) targets and inhibits the chaperonin-containing TCP-1 (CCT) protein-folding complex, is selectively cytotoxic to cancer cells, and is non-toxic to normal tissue. With the delivery of CT20p to prostate cancer cells via PSMA, a dual level of cancer specificity is achieved: (1) selective targeting to PSMA-expressing prostate tumors, and (2) specific cytotoxicity to cancer cells with minimal toxicity to normal cells. The PSM...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Orielyz Flores, Santimukul Santra, Charalambos Kaittanis, Rania Bassiouni, Amr S Khaled, Annette R. Khaled, Jan Grimm, J Manuel Perez Tags: Research Paper Source Type: research

High-Yield Synthesis of Monomeric LMWP(CPP)-siRNA Covalent Conjugate for Effective Cytosolic Delivery of siRNA
Because of the unparalleled efficiency and universal utility in treating a variety of disease types, siRNA agents have evolved as the future drug-of-choice. Yet, the inability of the polyanionic siRNA macromolecules to cross the cell membrane remains as the bottleneck of possible clinical applications. With the cell penetrating peptides (CPP) being discovered lately, the most effective tactic to achieve the highest intracellular siRNA delivery deems to be by covalently conjugating the drug to a CPP; for instance, the arginine-rich Tat or low molecular weight protamine (LMWP) peptides. However, construction of such a chemic...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Junxiao Ye, Ergang Liu, Junbo Gong, Jianxin Wang, Yongzhuo Huang, Huining He, Victor C. Yang Tags: Research Paper Source Type: research

Fabrication of Tissue-Engineered Bionic Urethra Using Cell Sheet Technology and Labeling By Ultrasmall Superparamagnetic Iron Oxide for Full-Thickness Urethral Reconstruction
Urethral strictures remain a reconstructive challenge, due to less than satisfactory outcomes and high incidence of stricture recurrence. An “ideal” urethral reconstruction should establish similar architecture and function as the original urethral wall. We fabricated a novel tissue-engineered bionic urethras using cell sheet technology and report their viability in a canine model. Small amounts of oral and adipose tissues were harvested, and adipose-derived stem cells, oral mucosal epithelial cells, and oral mucosal fibroblasts were isolated and used to prepare cell sheets. The cell sheets were hierarchically ...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Shukui Zhou, Ranxin Yang, Qingsong Zou, Kaile Zhang, Ting Yin, Weixin Zhao, Joseph G. Shapter, Guo Gao, Qiang Fu Tags: Research Paper Source Type: research

Rapid In Situ MRI Traceable Gel-forming Dual-drug Delivery for Synergistic Therapy of Brain Tumor
Preventing tumor recurrence after surgical resection of a brain tumor is a significant clinical challenge because current methods deliver chemotherapeutic agents in a rapid manner and are not effective against the residual tumor cells. To overcome this drawback, we report a simple method to prepare magnetic resonance imaging (MRI) traceable ultra-thermosensitive hydrogels with rapid gelation ability from aqueous solution within 4 s at 28 °C for hydrophilic (epirubicin, EPI) and hydrophobic (paclitaxel, PTX) drugs co-delivery with bovine serum albumin nanoparticles (BSA NPs) incorporation. The results showed the average...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Feng-Wei Lin, Pin-Yuan Chen, Kuo-Chen Wei, Chiung-Yin Huang, Chih-Kuang Wang, Hung-Wei Yang Tags: Research Paper Source Type: research