In JoVE (1)
Other Publications (10)
- Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi = Zhonghua Laodong Weisheng Zhiyebing Zazhi = Chinese Journal of Industrial Hygiene and Occupational Diseases
- Biochemical and Biophysical Research Communications
- Molecular Pharmaceutics
- Nanomedicine : Nanotechnology, Biology, and Medicine
- Journal of Controlled Release : Official Journal of the Controlled Release Society
- Journal of Digestive Diseases
- Frontiers in Plant Science
Articles by Rui Xue Zhang in JoVE
Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice Rui Xue Zhang1, Tian Zhang1, King Chen1, Ji Cheng1, Paris Lai1, Andrew M. Rauth2, K. Sandy Pang1, Xiao Yu Wu1 1Department of Pharmaceutical Sciences, University of Toronto, 2Departments of Medical Biophysics and Radiation Oncology, University of Toronto, Ontario Cancer Institute, University Health Network This protocol describes an efficient and convenient analytical process of sample extraction and simultaneous determination of multiple drugs, doxorubicin (DOX), mitomycin C (MMC) and a cardio-toxic DOX metabolite, doxorubicinol (DOXol), in the biological samples from a preclinical breast tumor model treated with nanoparticle formulations of synergistic drug combination.
Other articles by Rui Xue Zhang on PubMed
Protocadherin-7 Induces Bone Metastasis of Breast Cancer Biochemical and Biophysical Research Communications. Jul, 2013 | Pubmed ID: 23751349 Breast cancer had a propensity to metastasize to bone, resulting in serious skeletal complications associated with poor outcome. Previous study showed that Protocadherin-7 (PCDH7) play an important role in brain metastatic breast cancer, however, the role of PCDH7 in bone metastatic breast cancer has never been explored. In the present study, we found that PCDH7 expression was up-regulation in bone metastatic breast cancer tissues by real-time PCR and immunohistochemistry assays. Furthermore, suppression of PCDH7 inhibits breast cancer cell proliferation, migration, and invasion in vitro by MTT, scratch, and transwell assays. Most importantly, overexpression of PCDH7 promotes breast cancer cell proliferation and invasion in vitro, and formation of bone metastasis in vivo. These data provide an important insight into the role of PCDH7 in bone metastasis of breast cancer.
Orexin-A-induced ERK1/2 Activation Reverses Impaired Spatial Learning and Memory in Pentylenetetrazol-kindled Rats Via OX1R-mediated Hippocampal Neurogenesis Peptides. Apr, 2014 | Pubmed ID: 24321199 Epilepsy is characterized by the occurrence of repetitive seizures and can greatly affect a patient's cognition, particularly in terms of learning and memory. Orexin-A is an excitatory neuropeptide produced by the lateral hypothalamus that has been shown to be involved in learning and memory. A reduction in the levels of orexin-A after seizures may underlie the learning and memory impairments induced by epilepsy. Thus, we used pentylenetetrazol (PTZ)-kindled rats to investigate the effects of orexin-A on learning and memory and the involvement of neurogenesis in the dentate gyrus in OX1R-mediated ERK1/2 activation. A Morris water maze test revealed reduced escape latencies, prolonged times in the target quadrant and an increased number of platform crossings in PTZ-kindled rats exposed to orexin-A. These ameliorating effects of orexin-A on spatial learning and memory were attenuated by the intracerebroventricular injection of the OX1R antagonist SB334867 or the ERK1/2 inhibitor U0126. Further studies using bromodeoxyuridine (BrdU) revealed that orexin-A increased the number of BrdU-positive cells, doublecortin (DCX)/BrdU levels and the number of NeuN/BrdU double-positive nuclei in the dentate gyrus of PTZ-kindled rats. However, these effects were inhibited by treatment with SB334867 or U0126. Taken together, these data suggest that orexin-A attenuated the impairment of spatial learning and memory in PTZ-kindled rats and that this attenuation involved neurogenesis in the dentate gyrus via OX1R-mediated ERK1/2 activation.
Synergistic Nanoparticulate Drug Combination Overcomes Multidrug Resistance, Increases Efficacy, and Reduces Cardiotoxicity in a Nonimmunocompromised Breast Tumor Model Molecular Pharmaceutics. Aug, 2014 | Pubmed ID: 24830351 Anthracyclines, commonly employed for cancer chemotherapy, suffer from dose-limiting cardiotoxicity and poor efficacy due to multidrug resistance (MDR). We previously demonstrated that simultaneous delivery of the synergistic drugs doxorubicin (DOX) and mitomycin C (MMC) by polymer-lipid hybrid nanoparticles (PLN) circumvented MDR, increased efficacy, and reduced cardiotoxicity in immuncompromised mice superior to poly(ethylene glycol)-coated (PEGylated) lipososmal DOX (PLD). Herein it is shown that the DOX-MMC combination was also synergistic in MDR EMT6/AR1 murine breast cancer cells and that their nanoparticle formulations were able to overcome the MDR phenotype. In contrast PLD exhibited little or no effect on the MDR cells. For the first time, these differences in in vitro efficacy are shown to be strongly correlated with cellular uptake and intracellular distribution of DOX brought about by DOX formulations (e.g., free solution, PLN vs PLD). To take into consideration the role of an intact immune system and tumor stroma in the response of host and tumor to chemotherapy, use was made of nonimmunocomprised mouse models to study the dose tolerance, cardiotoxicity, and efficacy of DOX-MMC coloaded PLN (DMsPLN) compared to PLD. DMsPLN treatment at 50 mg/m(2) DOX and 17 mg/m(2) of MMC singly or once every 4 days for 4 cycles were well tolerated by the mice without elevated systemic toxicity blood markers or myocardial damage. In contrast, PLD was limited to a single treatment due to significant total weight loss. The DMsPLN treatment delayed tumor growth up to 312% and 28% in EMT6/WT and EMT6/AR1 models, respectively. This work supports the translational value of DMsPLN for the aggressive management of either naïve or anthracycline-resistant tumors.
YAP and TAZ Take Center Stage in Cancer Biochemistry. Nov, 2015 | Pubmed ID: 26465056 The Hippo pathway was originally identified and named through screening for mutations in Drosophila, and the core components of the Hippo pathway are highly conserved in mammals. In the Hippo pathway, MST1/2 and LATS1/2 regulate downstream transcription coactivators YAP and TAZ, which mainly interact with TEAD family transcription factors to promote tissue proliferation, self-renewal of normal and cancer stem cells, migration, and carcinogenesis. The Hippo pathway was initially thought to be quite straightforward; however, recent studies have revealed that YAP/TAZ is an integral part and a nexus of a network composed of multiple signaling pathways. Therefore, in this review, we will summarize the latest findings on events upstream and downstream of YAP/TAZ and the ways of regulation of YAP/TAZ. In addition, we also focus on the crosstalk between the Hippo pathway and other tumor-related pathways and discuss their potential as therapeutic targets.
Polymer-lipid Hybrid Nanoparticles Synchronize Pharmacokinetics of Co-encapsulated Doxorubicin-mitomycin C and Enable Their Spatiotemporal Co-delivery and Local Bioavailability in Breast Tumor Nanomedicine : Nanotechnology, Biology, and Medicine. Jul, 2016 | Pubmed ID: 26772427 Effective combination chemotherapy requires the delivery of drugs of synergism to tumor sites while sparing normal tissues. Herein we investigated whether coencapsulation of doxorubicin and mitomycin C within polymer-lipid hybrid nanoparticles (DMPLN) achieved this goal via ratiometric drugs in an orthotopic murine breast tumor model with nanocarrier-modified biodistribution, pharmacokinetics, local bioavailability and toxicity. Fluorescence imaging revealed quickened and extended tumor uptake but reduced cardiac accumulation of DMPLN. Quantitative drug analysis demonstrated prolonged systemic circulation, increased tumor accumulation and sustained synergistic ratios of doxorubicin and mitomycin C delivered by DMPLN over 24h. Higher levels of tumor cell apoptosis and reduced organ toxicity were obtained with DMPLN compared to free drug cocktails. DMPLN released DOX in tumors more efficiently than that from liposomal doxorubicin, as evidenced by a higher extent of the metabolite, doxorubicinol. These findings substantiate the importance of rational design of nanoparticles for synergistic drug combination therapy.
Nanomedicine of Synergistic Drug Combinations for Cancer Therapy - Strategies and Perspectives Journal of Controlled Release : Official Journal of the Controlled Release Society. Oct, 2016 | Pubmed ID: 27287891 Nanomedicine of synergistic drug combinations has shown increasing significance in cancer therapy due to its promise in providing superior therapeutic benefits to the current drug combination therapy used in clinical practice. In this article, we will examine the rationale, principles, and advantages of applying nanocarriers to improve anticancer drug combination therapy, review the use of nanocarriers for delivery of a variety of combinations of different classes of anticancer agents including small molecule drugs and biologics, and discuss the challenges and future perspectives of the nanocarrier-based combination therapy. The goal of this review is to provide better understanding of this increasingly important new paradigm of cancer treatment and key considerations for rational design of nanomedicine of synergistic drug combinations for cancer therapy.
Design of Nanocarriers for Nanoscale Drug Delivery to Enhance Cancer Treatment Using Hybrid Polymer and Lipid Building Blocks Nanoscale. Jan, 2017 | Pubmed ID: 27973629 Polymer-lipid hybrid nanoparticles (PLN) are an emerging nanocarrier platform made from building blocks of polymers and lipids. PLN integrate the advantages of biomimetic lipid-based nanoparticles (i.e. solid lipid nanoparticles and liposomes) and biocompatible polymeric nanoparticles. PLN are constructed from diverse polymers and lipids and their numerous combinations, which imparts PLN with great versatility for delivering drugs of various properties to their nanoscale targets. PLN can be classified into two types based on their hybrid nanoscopic structure and assembly methods: Type-I monolithic matrix and Type-II core-shell systems. This article reviews the history of PLN development, types of PLN, lipid and polymer candidates, fabrication methods, and unique properties of PLN. The applications of PLN in delivery of therapeutic or imaging agents alone or in combination for cancer treatment are summarized and illustrated with examples. Important considerations for the rational design of PLN for advanced nanoscale drug delivery are discussed, including selection of excipients, synthesis processes governing formulation parameters, optimization of nanoparticle properties, improvement of particle surface functionality to overcome macroscopic, microscopic and cellular biological barriers. Future directions and potential clinical translation of PLN are also suggested.
Hypertriglyceridemic Acute Pancreatitis in Emergency Department: Typical Clinical Features and Genetic Variants Journal of Digestive Diseases. Jun, 2017 | Pubmed ID: 28548292 To investigate the clinical characteristics of patients with hypertriglyceridemic acute pancreatitis (HTGAP), and the molecular foundation contributing to hypertriglyceridemia in such patients.
Root Damage Under Alkaline Stress Is Associated with Reactive Oxygen Species Accumulation in Rice (Oryza Sativa L.) Frontiers in Plant Science. 2017 | Pubmed ID: 28943882 Alkaline stress (high pH) severely damages root cells, and consequently, inhibits rice (Oryza sativa L.) seedling growth. In this study, we demonstrate the accumulation of reactive oxygen species (ROS) in root cells under alkaline stress. Seedlings of two rice cultivars with different alkaline tolerances, 'Dongdao-4' (moderately alkaline-tolerant) and 'Jiudao-51' (alkaline-sensitive), were subjected to alkaline stress simulated by 15 mM sodium carbonate (Na2CO3). Alkaline stress greatly reduced seedling survival rate, shoot and root growth, and root vigor. Moreover, severe root cell damage was observed under alkaline stress, as shown by increased membrane injury, malondialdehyde accumulation, and Evan's Blue staining. The expression of the cell death-related genes OsKOD1, OsHsr203j, OsCP1, and OsNAC4 was consistently upregulated, while that of a cell death-suppressor gene, OsBI1, was downregulated. Analysis of the ROS contents revealed that alkaline stress induced a marked accumulation of superoxide anions ([Formula: see text]) and hydrogen peroxide (H2O2) in rice roots. The application of procyanidins (a potent antioxidant) to rice seedlings 24 h prior to alkaline treatment significantly alleviated alkalinity-induced root damage and promoted seedling growth inhibition, which were concomitant with reduced ROS accumulation. These results suggest that root cell damage, and consequently growth inhibition, of rice seedlings under alkaline stress is closely associated with ROS accumulation. The antioxidant activity of superoxide dismutase, catalase, peroxidase, and ascorbate peroxidase increased under alkaline stress in the roots, probably in response to the cellular damage induced by oxidative stress. However, this response mechanism may be overwhelmed by the excess ROS accumulation observed under stress, resulting in oxidative damage to root cells. Our findings provide physiological insights into the molecular mechanisms of alkalinity-induced damage to root cells, and will contribute to the improvement of alkaline stress tolerance in rice plants.