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Biomedical subjects

Zhi Yang

Publications and source records attributed to Zhi Yang.

31 records · Page 2Linked to original sources

Effects of moisture and temperature on the osteoinductivity of demineralized bone matrix.

Demineralized bone matrix (DBM) is a well established osteoinductive bone graft material. It has been mixed with a variety of carriers to adjust to different forms of handling for a variety of applications. The impact of the various carriers on osteoinductivity remains largely unknown. Using an in vitro cell culture assay and in vivo intramuscular implantations into nude rats, the effects of moisture from water-based carriers and the storage temperature on osteoinductivity were studied. In the dry state, DBM can preserve its osteoinductive activity when temperatures reached 65 degrees C, but in the presence of moisture, the activity decreases with incubation time. Nearly 90% of the DBM activity is lost when maintained for 5 weeks at 65 degrees C. This study further indicates that the structure and stability of the collagen network in DBM not only provide a scaffold for osteogenitor cell proliferation and differentiation, but also controls the release rate of osteoinductive growth factors.

Alkaline Phosphatase↗

Chitosan/gelatin-based films crosslinked by proanthocyanidin.

Novel polymer networks consisting of crosslinked gelatin/chitosan were prepared by a solution casting technique. Methods for bulk crosslinking were developed to modify the gelatin/chitosan blends with the use of a nontoxic crosslinking reagent, proanthocyanidin (PA). FTIR spectral analyses of the preparations showed network formations of crosslinked gelatin, chitosan, and PA by amide and ester linkages. The crosslinked networks were stable in the aqueous state, and had improved mechanical properties and thermal stability when compared with nonlinked gelatin (G) and chitosan/gelatin (C/G) films. In vitro protease digestion and cell-culture studies showed that the PA-crosslinked C/G films are nontoxic and exhibited decreased biodegradation rate and a better ability to support cell adhesion and proliferation than noncrosslinked gelatin or chitosan alone. These results suggest that such a nontoxic crosslinked gelatin/chitosan scaffold can become a promising matrix for tissue-engineering applications.

Animals↗

Plaque imaging using ultrasound, magnetic resonance and computer tomography: a review.

Different classifications have been proposed in the literature for the characterization of atherosclerotic plaque morphology, resulting in considerable confusion. For example plaques containing medium of high level uniform echoes were classified as homogeneous by others and correspond closely to dense and calcified plaques, other types. This survey is to understand different types of plaque when imaged using ultrasound and MR.

Humans↗

[Survey scheme of the main Chinese medicines resources].

The survey of Chinese medicines resources concerns the development of the traditional Chinese medicine industry. It also directly influences the modernization process of traditional Chinese medicines. Owing to lacking of the scientific data on the Chinese medicines resources, it is a extremely urgent work to carry out survey of main Chinese medicine resources in nationwide. This paper explains the meaning and necessity. And it also investigated the survey object, contents, new technologies and methods.

Conservation of Natural Resources↗

Characterization of an anti-human ovarian carcinomaxanti-human CD3 bispecific single-chain antibody with an albumin-original interlinker.

OBJECTIVE: The objective of this study was to determine the properties of a single-chain bispecific antibody (scBsAb) against human ovarian carcinoma and to develop this agent for potential use in human ovarian cancer. METHODS: ELISA and FACS were performed to determine the antigen-binding properties of the scBsAb. Its abilities to retarget the pre-activated human peripheral blood mononuclear cells (PBMCs) to human ovarian carcinoma cell line SKOV3 cells and mediate their lysis in vitro were performed by a colorimetric MTT-based assay. Nude mice bearing human SKOV3 tumor xenografts were used to study the distribution and imaging of the scBsAb. Its pharmacokinetics in vivo was also studied in naive BALB/c mice. RESULTS: The scBsAb showed nearly identical ligand binding properties at each site relative to the individual monovalent single-chain antibody prototype molecules and could bridge SKOV3 and human T cell line Jurkat, which expresses CD3 antigens on the surface of cells together. It can also retarget the pre-activated PBMCs to SKOV3 cells and mediated their lysis in vitro effectively. Imaging and distribution study demonstrated that the antibody could target the tumor. Its elimination in vivo corresponded to second-order kinetics with a terminal half-life time (t(1/2)beta) of 7.7 h. CONCLUSION: This scBsAb with easy production and reasonable blood retention time should be developed for potential use in human ovarian cancer.

Albumins↗

Sensitization to radiation from an implanted 125I source by sustained intratumoral release of chemotherapeutic drugs.

We have investigated tumor response to low-dose-rate irradiation from an implanted 125I source alone or in conjunction with intratumoral drug administration. The drug (cis-DDP or 5-FU) was incorporated homogeneously into the co-polymer CPP-SA, 20:80, and the polymer/drug rods were implanted in the RIF-1 fibrosarcomas growing subcutaneously in C3H mice. Twenty-four hours later, the tumor was implanted with an 125I seed. Tumor growth time was the end point in these experiments. For implanted 125I sources of different dose rates and implant times giving a range of total doses, a consistent dose-response relationship was shown between tumor growth time and total dose. In other experiments, 125I sources of different specific activities were implanted for periods of time adjusted so that the total dose to the tumor was always the same. When the 125I implant was combined with 5-FU, greater than additive responses were seen for both short (30 h) and long (96 h) 125I treatment times. In contrast, a short-duration (30 h) 125I implant combined with cis-DDP was the least effective treatment, giving a combined response that was no better than additive, whereas 96 h exposure to 125I combined with cis-DDP was the most effective combined treatment. It is conjectured that this inverse dose-rate effect seen when cis-DDP is combined with low-dose rate radiation is related to a cell cycle effect and/or to inhibition of repair of radiation damage by cis-DDP.

Animals↗

Effects of bushen huoxue decoction on nitric oxide (NO) in serum, articular cartilage and synovium in rabbits of knee osteoarthritis.

UNLABELLED: Forty-eight New Zealand rabbits were divided into normal group (n=18), control group (n=18) and Chinese herbs treatment group (n=12) randomly. The rabbits in the normal group received sham-operation, and the OA model was established by Hulth's method. All the rabbits in the treatment group were given bushen huoxue decoction from the 6th week after the operation. At 6th, 8th and 12th week after the operation, the NO concentrations of the serum, joint cartilage and synovium were examined. RESULTS: Indicated that the NO concentrations of the serum, joint cartilage and synovium in the control group were all significantly higher than those in the normal group, with the joint cartilage more obvious (P<0.05). In the Chinese herbs treatment group the NO concentrations in all the parts obviously decreased as compared with the control group (P<0.05). It is suggested that bushen huoxue decoction decrease the levels of NO in the serum, synovium and joint cartilage in the OA rabbit.

Animals↗

Replication inhibitors modulate instability of an expanded trinucleotide repeat at the myotonic dystrophy type 1 disease locus in human cells.

Gene-specific CTG/CAG repeat expansion is associated with at least 14 human diseases, including myotonic dystrophy type 1 (DM1). Most of our understanding of trinucleotide instability is from nonhuman models, which have presented mixed results, supporting replication errors or processes independent of cell division as causes. Nevertheless, the mechanism occurring at the disease loci in patient cells is poorly understood. Using primary fibroblasts derived from a fetus with DM1, we have shown that spontaneous expansion of the diseased (CTG)(216) allele occurred in proliferating cells but not in quiescent cells. Expansions were "synchronous," with mutation frequencies approaching 100%. Furthermore, cells were treated with agents known to alter DNA synthesis but not to directly damage DNA. Inhibiting replication initiation with mimosine had no effect upon instability. Inhibiting both leading- and lagging-strand synthesis with aphidicolin or blocking only lagging strand synthesis with emetine significantly enhanced CTG expansions. It was striking that only the expanded DM1 allele was altered, leaving the normal allele, (CTG)(12), and other repeat loci unaffected. Standard and small-pool polymerase chain reaction revealed that inhibitors enhanced the magnitude of short expansions in most cells threefold, whereas 11%-25% of cells experienced gains of 122-170 repeats, to sizes of (CTG)(338)-(CTG)(386). Similar results were observed for an adult DM1 cell line. Our results support a role for the perturbation of replication fork dynamics in DM1 CTG expansions within patient fibroblasts. This is the first report that repeat-length alterations specific to a disease allele can be modulated by exogenously added compounds.

Aphidicolin↗

Ligand-free Heck reaction: Pd(OAc)2 as an active catalyst revisited.

Palladium acetate was shown to be an extremely active catalyst for the Heck reaction of aryl bromides. Both the base and the solvent were found to have a fundamental influence on the efficiency of the reaction, with K(3)PO(4) and N,N-dimethylacetamide being the optimal base and solvent, respectively.

Journal Article↗

Clinical application of radioimmunoguided surgery in colorectal cancer using 125I-labeled carcinoembryonic antigen-specific monoclonal antibody submucosally.

PURPOSE: The aim of this study was to evaluate the applicability of 125I-labeled carcinoembryonic antigen-specific monoclonal antibody CL58 in clinical radioimmunoguided surgery for colorectal cancer. METHODS: First, we tested the purity and affinity constant of CL58 and measured the binding affinity of CL58 to colorectal cancer cells and normal cells. Second, we injected 125I-labeled CL58 into nude mice with colon cancers. Then, samples from the tumor, blood, and normal tissues of injected mice were weighed and counted in a gamma-ray counter for assessment of biodistribution. Finally, we administered 125I-labeled CL58 submucosally in 29 patients with colorectal cancer via endoscope. Radioimmunoguided surgery was performed 3 to 14 days later with a portable gamma-detecting probe to obtain the counts in the target sites. Tumor-to-normal tissue ratio of 3 was taken as the lowest positive threshold value for primary lesions, wall infiltration, and lymph node metastasis. In addition, all the samples were examined by routine histopathology. Lymph nodes negative by routine histopathology were subjected to immunohistochemical staining with anticytokeratin to detect the lymphatic micrometastasis. RESULTS: The affinity constant of CL58 was 7.5 x 109 M-. Moreover, CL58 reacted strongly to the colorectal cancer cell lines, but not to the normal control cells. Furthermore, the tumor tissues showed significant intake of 125I-labeled CL58, as compared with that of normal tissues. The sensitivity of radioimmunoguided surgery in detecting primary lesions was 93.1 percent, and the specificity of radioimmunoguided surgery to correctly identify negative incisional margins for tumor infiltration was 95.5 percent. For the detection of lymphatic metastasis, the sensitivity of radioimmunoguided surgery was 92.0 percent and the specificity was 87.8 percent. The sensitivity of radioimmunoguided surgery in detecting lymph node metastasis was significantly higher when compared with traditional clinical methods (P = 0.0087). The specificity of radioimmunoguided surgery to identify negative incisional margins was also significantly higher when compared with traditional clinical methods (P = 0.0117). The sensitivity and specificity of radioimmunoguided surgery in detecting lymph nodes metastasis showed statistical significance, as compared with traditional clinical methods. Immunohistochemistry verified the existence of lymphatic micrometastasis in radioimmunoguided surgery-positive but histology-negative lymph nodes. CONCLUSIONS: This study indicates that radioimmunoguided surgery for colorectal cancer using 125I-labeled anticarcinoembryonic antigen monoclonal antibody submucosally enables surgeons to define lymphatic metastasis, thus successfully guiding surgeons in performing personalized radical operation.

Adult↗

Tumor treatment by sustained intratumoral release of 5-fluorouracil: effects of drug alone and in combined treatments.

PURPOSE: To evaluate an intratumoral polymer implant for sustained delivery of 5-fluorouracil (5-FU) in a mouse tumor model. METHODS AND MATERIALS: 5-FU was incorporated into a polyanhydride-based polymer, bis(p-carboxyphenoxy)propane sebacic acid (CPP:SA) and implanted in RIF-1 mouse fibrosarcoma growing s.c. The effectiveness of treatment was evaluated by tumor growth delay. External beam radiation was 60Co gamma rays, and the source of interstitial radiation was implanted 125I seeds. A second drug, cis-diamminedichloroplatinum (cis-DDP), was administered by intraperitoneal injection or by osmotic pump. RESULTS: For drug/polymer implant alone, the tumor growth delay was proportional to the amount of drug in the implant. The 5-FU polymer implant was most effective when combined with cis-DDP or with acute or fractionated radiation, and in some cases, the effects of combined treatments were greater than additive. The most effective combination was intratumoral 5-FU and low-dose-rate radiation delivered from an interstitial radiation source. CONCLUSION: Results indicate that 5-FU can be effectively delivered by polymer implant and that this mode of delivery is particularly appropriate for combined treatments.

Animals↗

Pre-clinical study on tumor vasoactive intestinal peptide receptor scintigraphy.

OBJECTIVE: To develop a tumor imaging agent for vasoactive intestinal peptide (VPAC) receptor and evaluate its biological activity and pharmacokinetics of radiolabeled peptide. METHODS: VIP(28) was modified at the carboxyl terminal by the addition of His-tag which was the chelating site of (99m)Tc(I) and the general purification tag for immobilized metal ion affinity chromatography. Biological activity of the modified VIP(28) analogue MY34 was examined in vitro by radiological cell-binding assay, rabbit internal anal sphincter (IAS) smooth muscle relaxing assay and immunocytochemical stain. The pharmacokinetics of this labeled peptide was examined in C57 mice. RESULTS: MY34 could relax the IAS smooth muscle and bind VPAC receptors on tumor cell membranes. (99m)Tc- MY34, with a yield of about 90%, was stable enough for practical use. Both MY34 and VIP(28) could inhibit the binding between the labeled peptide and VPAC receptor. The pharmacokinetics of [(99m)Tc(H(2)O)(3)(CO)(3)]-MY34 was studied in mice conformed well with the two-compartment model (Wi = 1/C(2)), with a t(1)/(2alpha) of 16.35 min and a t(1)/(2beta) of 1013.56 min. CONCLUSION: MY34 possesses physiological activities and specific receptor binding characteristics similar to those of natural VIP(28).

3T3 Cells↗

99mTc-labeled cyclic RGDfK dimer: initial evaluation for SPECT imaging of glioma integrin alphavbeta3 expression.

This report describes the evaluation of biodistribution properties of three radiotracers, [(99m)Tc(SQ168)(EDDA)], [(99m)Tc(SQ168)(tricine)(PDA)], and [(99m)Tc(SQ168)(tricine)(TPPTS)] (SQ168 = [2-[[[5-[carboonyl]-2-pyridinyl]hydrazono]methyl]benzenesulfonic acid]-Glu(cyclo{Lys-Arg-Gly-Asp-d-Phe})-cyclo{Lys-Arg-Gly-Asp-d-Phe}; EDDA = ethylenediamine-N,N'-diacetic acid; PDA = 2,5-pyridinedicarboxylic acid; TPPTS = trisodium triphenylphosphine-3,3',3' '-trisulfonate), and their potential to image the glioma integrin alpha(v)beta(3) expression in BALB/c nude mice bearing the U87MG human glioma xenografts. It was found that all three radiotracers were able to localize in glioma tumors with a relatively high tumor uptake and long tumor retention time by binding to the integrin alpha(v)beta(3) expressed on both tumor cells and endothelial cells of tumor neovasculature. It seems that the coligand has minimal effect on integrin alpha(v)beta(3) targeting capability of the (99m)Tc-labeled RGDfK dimer, but it has a significant impact on their biodistribution properties. For example, the complex [(99m)Tc(SQ168)(tricine)(TPPTS)] has the lowest liver uptake and the highest metabolic stability in normal BALB/c nude mice. Results from SPECT imaging studies show that the glioma tumors can be clearly visualized with all three radiotracers at 4 h postinjection. Among the three radiotracers evaluated in this study, [(99m)Tc(SQ168)(tricine)(TPPTS)] has the best imaging quality and is a promising candidate for more preclinical evaluations in the future.

Animals↗