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Biomedical subjects

Su Zhang

Publications and source records attributed to Su Zhang.

9 recordsLinked to original sources

SVM for density estimation and application to medical image segmentation.

A method of medical image segmentation based on support vector machine (SVM) for density estimation is presented. We used this estimator to construct a prior model of the image intensity and curvature profile of the structure from training images. When segmenting a novel image similar to the training images, the technique of narrow level set method is used. The higher dimensional surface evolution metric is defined by the prior model instead of by energy minimization function. This method offers several advantages. First, SVM for density estimation is consistent and its solution is sparse. Second, compared to the traditional level set methods, this method incorporates shape information on the object to be segmented into the segmentation process. Segmentation results are demonstrated on synthetic images, MR images and ultrasonic images.

Humans↗

[Studies on the chemical constituents from Caragana intermedia].

OBJECTIVE: To study the chemical constituents from Caragana intermedia. METHODS: The compounds were separated by chromatography methods. Their structures were identified by spectral analysis. RESULTS: Eight compounds were isolated and identified as 7,5'-dihydroxy-3 '-methoxyisoflavone-7-O-beta-D-glucoside (1), isorhamnetin 7-O-alpha-L-rhamnoside (2), 3, 4-dihydroxybenzoic acid (3), N-trans-caffeoyltyramine (4), D-3-O-methyl-inositol (5),7alpha-hydroxy-beta-sitosterol (6),7beta-hydroxy-beta-sitosterol (7) and stearic acid (8). CONCLUSION: All these compounds were obtained from this plant for the first time.

Caragana↗

Metabolites and the pharmacokinetics of kobophenol A from Caragana sinica in rats.

This research aims to study the metabolism and pharmacokinetics of phytoestrogen kobophenol A (1), the main active compound of Caragana sinica (Buc'hoz) Rehd. (Fabaceae), in rats. Metabolites of 1 in rats' feces were isolated and purified by multi-chromatograph techniques; three new metabolites of 1, named koboquinone A (M1), koboquinone B (M2) and koboquinone C (M3), were isolated, purified from rats' feces after they being orally administered with 1. Structure identification of the metabolites was fulfilled by spectroscopic analysis. M1 and M2 are structurally different to those natural occurring stilbene tetramers, which also have para-quinone structure. M1 also showed the activity of stimulating the proliferation of cultured osteoblasts. The pharmacokinetics of 1 in rats could be described by a two-compartmental model (P<0.05). The half-life was 0.68 h for i.v. administration and 5.78 h for oral administration. The oral bioavailability of 1 was calculated to be 2.0%; rats tissue distribution experiments show that 1 was prominently concentrated in livers. Both of the low oral bioavailability and the rapid reduction of 1 in blood indicated a suitable formulation is needed while it is developed as a new drug.

Animals↗

A delayed chemically induced tumorigenesis in Brca2 mutant mice.

BRCA2 is a breast cancer susceptibility gene. Germline mutations of BRCA2 account for about 10-30% of familial breast cancer cases. Consistent with its tumor-suppressor activity, BRCA2 plays an important role in DNA repair. To assess the susceptibility of carriers of mutant BRCA2 to tumorigenesis induced by DNA-damaging carcinogens, we generated a Brca2 knockout mouse strain and studied its susceptibility to chemically induced tumorigenesis. Similar to previously reported Brca2 knockout mice, our Brca2-/- embryos die at E8.5-9.5, while the Brca2+/- mice are tumor-free and fertile. Unexpectedly, Brca2+/- mice developed tumors slower than did their wild-type littermates when treated with a potent carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). In vitro experiments showed that Brca2+/- mouse cells and Capan-1 cells, a human pancreatic cancer cell line deficient of BRCA2, were more sensitive to DMBA-induced apoptosis, than were Brca2+/+ mouse cells and a derivative of Capan-1 cells that expressed exogenous wild-type BRCA2, respectively. Our results suggest that enhanced sensitivity of Brca2 mutant cells to DMBA-induced apoptosis at the dose of DMBA we used contributes to the delayed tumorigenesis of Brca2+/- animals. This suggestion may also provide a rational explanation for a previous unexpected finding that cigarette smoking appears to reduce the breast cancer risk of BRCA2 mutation carriers.

9,10-Dimethyl-1,2-benzanthracene↗

Four new eudesmanes from Caragana intermedia and their biological activities.

Four new eudesmanes, namely, 4(15)-eudesmene-1beta,7alpha-diol (1), 4(15)-eudesmene-1beta,7beta-diol (2), 7-trinoreudesma-4(15),8-dien-1beta-ol-7-one (3), and eudesma-4(15),7-dien-1beta-ol (4), as well as three known compounds, 5-epi-eudesma-4(15)-ene-1beta,6beta-diol (5), 4(15)-eudesmene-1beta,6alpha-diol (6), and 4(15)-eudesmene-1beta,5alpha-diol (7), were isolated from the aerial part of Caragana intermedia. The structures were elucidated by spectroscopic and spectrometric analyses including 1D, 2D NMR, HRMS, and IR. The structures of compounds 1, 5, 6, and 7 were confirmed by X-ray crystallographic analysis. Compound 7 showed glucose consumption activity with an IC value of 10.7 microg/mL in a C2C12 muscle cell assay. The MIC value of this compound (100 mg/kg) in a db/db mice model is equivalent to that of metformin in vivo.

Anti-HIV Agents↗

[MDR-reversing effect of two components of catechin on human hepatocellular carcinoma BEL-7404/Adr in vitro].

BACKGROUND & OBJECTIVE: Catechin is composed of a variety of components,some of which have anti-cancer activity. There was no report on effect of catechin on the multidrug resistance of hepatocellular carcinoma so far. The aim of this study was to investigate the MDR-reversing effect of two components of catechin on human hepatocellular carcinoma BEL-7404/Adr in vitro and its potential mechanism. METHODS: MTT was used to test the toxicity of the two components of catechin. The concentration of the drugs inside the cells was determined by fluorospectro-photometry and the expression of MDR1 was measured by RT-PCR. RESULTS: The inhibition rates of BEL-7404/Adr caused by two components of catechin were less than 10% under the dose of 100 mg/L. Epicatechin gallate (ECG) in 60 mg/L or epigallocatechin gallate (EGCG) in 14 mg/L has slight cytotoxicity, but they could decrease the IC(50) of adriamycin (ADM) for BEL-7404/Adr from 36 mg/L to 2.3 mg/L or 1.9 mg/L, respectively, and the reversing folds were 15.8 and 19.2, respectively. The combined administration could increase the concentration of ADM in BEL-7404/Adr cells from 0.76 microg/10(8) cells-2.55 microg/10(8) cells to 2.04 microg/10(8) cells -9.28 microg/10(8) cells (P< 0.01). The expression of MDR1 was down-regulated by 27.6% and 41.3%, respectively. Furthermore, EGCG is the stronger one. CONCLUSION: ECG and EGCG can reverse the multi-drug resistance of human hepatocellular carcinoma in vitro. The possible mechanism is related to down-regulating the expression of MDR1 and raising the concentration of drugs inside the cells.

Carcinoma, Hepatocellular↗

Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues.

By using a cre-lox conditional knockout strategy, we report here the generation of androgen receptor knockout (ARKO) mice. Phenotype analysis shows that ARKO male mice have a female-like appearance and body weight. Their testes are 80% smaller and serum testosterone concentrations are lower than in wild-type (wt) mice. Spermatogenesis is arrested at pachytene spermatocytes. The number and size of adipocytes are also different between the wt and ARKO mice. Cancellous bone volumes of ARKO male mice are reduced compared with wt littermates. In addition, we found the average number of pups per litter in homologous and heterozygous ARKO female mice is lower than in wt female mice, suggesting potential defects in female fertility and/or ovulation. The cre-lox ARKO mouse provides a much-needed in vivo animal model to study androgen functions in the selective androgen target tissues in female or male mice.

Adipose Tissue↗

Inhibition of cancer cell growth by BRCA2.

The breast cancer susceptibility gene BRCA2 has been suggested to function as a "caretaker" of the genome. Cells without wild-type BRCA2 are deficient in repairing DNA damage. However, whether BRCA2 can also suppress oncogenesis by regulating cell proliferation remains to be determined. To address this question, the expression of wild-type BRCA2 protein was reconstituted, in an either constitutive or regulated manner, in the pancreatic cancer cell line Capan-1, which expresses only a mutant BRCA2. Expression of wild-type BRCA2 inhibited cell proliferation in culture and suppressed tumor growth in animals. Our results showed that, in addition to the DNA repair function, BRCA2 also suppresses tumor development by inhibiting cancer cell growth.

Animals↗

[GVHD Following Autologous Peripheral Blood Stem Cell Trasplantation Reduced Malignancy Relapse]

Administration of the immunosuppressive drug cyclosporine (CSA) after autologous peripheral blood stem cell transplantation (APBSCT) induces a systemic auto-immune syndrome resembling graft-versus-host disease (GVHD), this syndrome termed autologous GVHD has significant antitumor activity, it can reduce the incidence of tumor relapse after APBSCT. The antitumor effect of this auto-aggression syndrome can be enhanced by the administration of gamma-interferon (gamma-IFN). Five consecutive patients who received APBSCT received therapy inducing autologous GVHD. Intravenous administration of CSA [1 mg/(kg.d) for 28 days] was begin on the day of transplantation. gamma-interferon (0.025 mg/m(2) qod) was administered sub-cutaneously from days 7 throngh 28 after transplatation. Results showed that four of five occured autologous GVHD-skin demage, five in control didn't occur autologous GVHD. The relapse rate of the treated cases was 20% (1/5) versus 60% (3/5) of the control, and the median survival time of the treated cases was 20 (4 - 30) months versus 10 (2 - 20) months of the control. The data indicates that autologous GVHD results in low relapse rate of the patients rececving APBSCT.

Journal Article↗