Progress on utilizing mesenchymal stem cells as cellular delivery system for targeting delivery of as drug/gene for anti-tumor therapy / 浙江大学学报·医学版

Mesenchymal stem cells (MSCs) have the inherent tumor-homing ability with the attraction of multiple chemokines released by tumor tissues or tumor microenvironments, which can be utilized as promising cellular carriers for targeted delivery of anti-tumor drugs and genes. In most circumstances, large amount of systemicly administrated MSCs will be firstly trapped by lungs, following with re-distribution and homing to tumor tissues after lung clearance. Several approaches like enhanced interactions between chemokines and receptors on MSCs or reducing the retention of MSCs by changes of administration methods are firstly reviewed for improving the homing of MSCs towards tumor tissues. Additionally, the potentials and gains of utilizing MSCs to carry several chemotherapeutics, such as doxorubicin, paclitaxel and gemcitabine are summarized, showing the advantages of overcoming the short half-life and poor tumor targeting of these chemotherapeutics. Moreover, the applications of MSCs to protect and deliver therapeutic genes to tumor sites for selectively tumor cells eliminating or promoting immune system are highlighted. In addition, the potentials of using MSCs for tumor-targeting delivery of diagnostic and therapeutic agents are addressed. We believed that the continuous improvement and optimization of this stem cells-based cellular delivery system will provide a novel delivery strategy and option for tumor treatment.

Upregulation of miR-489-3p and miR-630 inhibits oxaliplatin uptake in renal cell carcinoma by targeting OCT2

Renal cell carcinoma (RCC) is one of the most common malignant tumors affecting the urogenital system, accounting for 90% of renal malignancies. Traditional chemotherapy options are often the front-line choice of regimen in the treatment of patients with RCC, but responses may be modest or limited due to resistance of the tumor to anticarcinogen. Downregulated expression of organic cation transporter OCT2 is a possible mechanism underlying oxaliplatin resistance in RCC treatment. In this study, we observed that miR-489-3p and miR-630 suppress OCT2 expression by directly binding to the OCT2 3'-UTR. Meanwhile, 786-O-OCT2-miRNAs stable expression cell models, we found that miRNAs could repress the classic substrate 1-methyl-4-phenylpyridinium (MPP), fluorogenic substrate ,-dimethyl-4-(2-pyridin-4-ylethenyl) aniline (ASP), and oxaliplatin uptake by OCT2 both and in xenografts. In 33 clinical samples, miR-489-3p and miR-630 were significantly upregulated in RCC, negatively correlating with the OCT2 expression level compared to that in adjacent normal tissues, using tissue microarray analysis and qPCR validation. The increased binding of c-Myc to the promoter of pri-miR-630, responsible for the upregulation of miR-630 in RCC, was further evidenced by chromatin immunoprecipitation and dual-luciferase reporter assay. Overall, this study indicated that miR-489-3p and miR-630 function as oncotherapy-obstructing microRNAs by directly targeting OCT2 in RCC.

Imaging performance of 18F-FDG PET-CT on patients with multiple myeloma / 实用肿瘤学杂志

Objective The objective of this study was to investigate the imaging findings of 18 F-FDG PET-CT in patients with multiple myeloma(MM).Methods Fifteen patients with multiple myeloma were enrolled in our hospital from January 2014 to October 2016.The clinical data of these patients were retrospectively analyzed to obtain the range of SUVmax values by 18F-FDG PET-CT imaging performance.Results Fifteen MM patients with 18F-FDG PET-CT showed a total number of lesions 202,the number of lesions 176 in PET and the number of lesions 171 in CT.The SUVmax range of 18F-FDG PET-CT imaging in the diagnosis of MM was 1.41 ～ 16.28.Fourteen cases of 15 MM patients were found varying degrees of bone destruction;one case showed a slightly increased bone density and also slightly increased FDG metabolic activity.Bone destruction was more performance for the chisel-like,osteolytic,swelling and flaky bone destruction.The osteogenesis lesions were rare.Conclusion 18F-FDG PET-CT imaging can clearly show the imaging features of MM by combining functional metabolic and anatomical information,and provide more clues for clinical diagnosis,which can improve the diagnostic accuracy of MM.

Research progress on the animal models and treatment strategies of diabetic foot ulcer / 浙江大学学报·医学版

The suitable experimental animal model is important in research of pathogenesis and therapeutic strategies of diabetic foot ulcer, and the murine model is the most commonly used one at present. It can be divided into two types: the animal model simulating pathological conditions and the model simulating clinical symptoms. This article reviews the current research progress on the mechanisms of diabetic ulcer pathogenesis, and relevant treatment strategies, including the inhibition of matrix metalloproteinases (MMPs) expression, promotion of angiogenesis and anti-inflammatory therapy.

Topical administration of traditional Chinese medicine and the methods for the promotion of drug penetration / 中国药科大学学报

@#Monomer component extracted from the herb is the main effective component of traditional Chinese medicine(TCM). Topical administrations of monomer component of TCM has attracted more and more attention due to the convenience of administration and the concentration enrichment in lesion. The main task for the studies of topical drug delivery system is to design the methods which can promote the penetration of the drugs. Currently, the main methods used to improve the penetration of monomer component of TCM includes the synthesis of different dosage forms and the application of physical and chemical techniques to facilitate the penetration of the drugs. This review summarizes the progress in different indications and mechanisms of diverse monomer components of TCM, different dosage forms, and physicochemical techniques used to facilitate drug penetration.

Research progress on application of carbon nanotubes in bone tissue engineering scaffold / 浙江大学学报·医学版

Carbon nanotubes possess excellent mechanical and electrical properties and demonstrate broad application prospects in medical fields. Carbon nanotubes are composed of inorganic materials, natural biodegradable polymer or synthetic biodegradable polymer. The composite bone tissue engineering scaffolds are constructed by particle-hole method, lyophilization, microsphere aggregation method, electrostatic spinning or three-dimensional printing. Composite scaffolds overcome the shortcomings of single material and have good biocompatibility, osteoconduction and osteoinduction. With the study of surface chemistry, toxicology, and biocompatibility, a degradable "human-friendly" carbon nanotubes composite bone tissue scaffold will be available; and under the drive of new fabrication techniques, the clinical application of carbon nanotubes composite bone tissue engineering scaffolds will be better developed.

Research progress of gene recombinant mesenchymal stem cells as tumor targeting delivery vehicles / 药学学报

The applications of targeting gene delivery systems in tumor therapy have attracted extensive attention of researchers in recent years, as they can selectively deliver the therapeutic gene to tumor sites, improve the success rate of gene therapy and reduce the side effects. Therefore, design and development of novel gene delivery vehicles have been a hot area of current research. Recent studies have shown that mesenchymal stem cells (MSCs) have the ability to migrate towards and engraft into the tumor sites. Therefore, these properties make them a great hope for efficient targeted-delivery vehicles in cancer gene therapy. In this review, we examine the promising of utilization of MSCs as a targeted-delivery vehicle for cancer gene therapy, and summarize various challenges and concerns regarding this therapy.

The effect of phonophoresis on transdermal delivery of sinomenine hydrochloride gel in vitro / 中华物理医学与康复杂志

Objective To study the effect of phonophoresis on transdermal delivery of sinomenine hydrochloride ( SH ) gel in vitro. Methods Ultrasound at one of two frequencies ( 800 kHz or 1 MHz) was applied with a sonicator with a transducer in this study. The skin of male Sprague-Dawley rats was used as the model and SH gel was used as the ultrasound couplant. The permeation rate of SH was detected using a modified Franz diffusion cell maintained at 32±0.5℃ and filled with 20% polyethylene glycol 400 physiological saline solution. The transdermal phonophoresis experiments were carried out in five groups: Group Ta, f=800 kHz, / = 0.75 W/cm2, t = 10 min:Group Tb,f=1 MHz,I=0.7 W/cm2, t=10 min; Group Tc,f=1 MHz,I=0.35 W/cm2, t=10 min; Group Td,f=800 kHz, I = 1.5 W/cm2, t = 10 min and Group Tc,f=800 kHz, I=1.5 W/cm2,t=5 min. There was also a control group (C) in which the SH was allowed to diffused passively. Samples were withdrawn at the indicated intervals and the concentration of SH was determined by high-performance liquid chromatography. The transdermal parameters such as average accumulated delivery quantity per unit area Q8h, average transdermal steady delivery rate J, and Tlag were calculated. Results The Q8h and Js of the control group were 20.65±10.23 μ/cm2 and 3.02±0.11μ/cm2/h respectively. The phonophoresis parameters in groups Ta and Tb were, on average, significantly higher than in the control group. The parameters in group Tb were significantly larger, on average, than in Te. In group Td the parameters were significantly larger than in groups Ta and Te. Conclusions The results show that phonophoresis can enhance the transdermal delivery of SH. Phonophoresis variables such as frequency and time influence its effects on drug permeation. Almost no change was observed in the structure of the skin after phonophoresis, though under a scanning electron microscope the surface of the corneum appeared rough and porous. Phonophoresis is there-fore an effective and safe method for SH transdermal delivery, and the effect is positively relation with the applied intensity and exposure time.