Biomedical subjects

Jiong Yang

Publications and source records attributed to Jiong Yang.

33 records · Page 2Linked to original sources

PubMed2004

Stepwise metastatic human hepatocellular carcinoma cell model system with multiple metastatic potentials established through consecutive in vivo selection and studies on metastatic characteristics.

PURPOSE: To establish a "stepwise metastatic human hepatocellular carcinoma (HCC) cell model system" for in-depth study of the underlying mechanisms of HCC metastasis. METHODS: Using MHCC97- a metastatic human hepatocellular carcinoma (HCC) cell line reported in 1999-as the parent cells, we subsequently established three cell lines (MHCC97-L, HMCC97-H, and HCCLM3) with increasing spontaneous metastatic potential. Now, the fourth cell line with unique multiple metastatic characteristics has been established by six rounds of in vivo selection. RESULTS: This cell line, designated as HCCLM6, is a polygonal epithelial cell with hypotriploid karyotype, the modal chromosomes are 55-58, and marker chromosomal abnormalities include i(1) (q10), i(8)(q10), der (4) t(4;8)(q31;q22), i(X)(q10). The cell population doubling time was 32 h. Fluorescent PCR showed HBV DNA integration in the cellular genome. Thirty-five days after HCCLM6 was injected subcutaneously into BALB/c nude mice, prominent lung metastases occurred in 100% of the recipient animals. When tumor tissue was orthotopically implanted into the liver of nude mouse, widespread loco-regional and pulmonary metastases occurred. Inoculation of this cell into the footpad of nude mice also produced 75% regional lymph node metastasis. Compared with MHCC97-L which was not metastastatic via subcutaneous or footpad inoculation and 40% metastatic via orthotopic inoculation, HCCLM6 had increased expression of matrix metalloproteinase (MMP-2 and MMP-9) and cytokeratin 19 (CK19), and decreased expression of Rb2/p130. The establishment of this new cell line has completed our stepwise metastatic HCC cell mode system, which was characterized by a similar genetic background but with significant differences in spontaneous metastasis behavior. CONCLUSIONS: The study supports the theory that cancer metastasis is a highly selective dynamic process and the cell model system could be a useful platform for the study of HCC metastasis.

Animals↗

PubMed2004

Synthesis of stereoisomeric medium-ring alpha,alpha'-dihydroxy cycloalkanones.

The stereochemical course of the epoxidation of the silyl enol ethers of 2-tert-butyldimethylsilyloxycycloheptanone and -cyclooctanone has been investigated and shown to proceed exclusively anti to the existing alpha-substituent. 2-(Benzyloxy)cyclooctanone behaves similarly, and the presence of a transannular double bond does not alter the outcome. Alpha-ketol rearrangements are seen to operate during ensuing fluoride ion-induced removal of the silyl protecting groups in select examples. The preferred means for generating the cis isomers of the alpha,alpha'-dihydroxy cycloalkanones involves methylenation of the monoprotected trans-dihydroxy ketones with the Nysted reagent, followed by oxidation and subsequent reduction with sodium borohydride. Ozonolysis and fluoride ion-induced desilylation complete the route.

Journal Article↗

PubMed2004

Interleukin-12 was not involved in promotion of T helper cell differentiation induced by theophylline.

AIM: To investigate the effect of theophylline on the naive T cell differentiation and the probable role of interleukin-12 (IL-12). METHODS: Naive cord blood T cells were treated with theophylline 10 mg/L for 3 d after stimulation with PHA 100 mg/L. Differentiation of T cells was analyzed by flow cytometry. Theophylline 10 mg/L and IL-12-mAb 0.025 mg/L were added in cord blood mononuclear cell (CBMC) cultures primed with LPS 1 mg/L to detect the levels of IL-12 and IL-12P40. The whole blood cultures were obtained from twelve health volunteers with or without administration of theophylline (200 mg). Cytokines were measured by enzyme linked immuno-sorbent assay. RESULTS: Theophylline promoted T helper 1 (Th1) cells differentiation from naive T cells (21.9 %+/-10.3 % vs 9.4 %+/-5.6 %, P<0.05), but had no significant effect on Th2 deviation. But theophylline inhibited the production of IL-12 and IL-12P40 by CBMC in vitro (28+/-6 ng/L vs 57+/-14 ng/L and 88+/-34 ng/L vs 214+/-82 ng/L, P<0.01) and reduced IL-12 and IL-12P40 levels in whole blood cultures from healthy subjects (19+/-11 ng/L vs 31+/-15 ng/L and 92+/-13 ng/L vs 196+/-49 ng/L, P<0.01). CONCLUSION: Theophylline promoted the differentiation of Th1 cells. IL-12 seemed not to be involved in this process.

Bronchodilator Agents↗

PubMed2004

Gene Ontology friendly biclustering of expression profiles.

The soundness of clustering in the analysis of gene expression profiles and gene function prediction is based on the hypothesis that genes with similar expression profiles may imply strong correlations with their functions in the biological activities. Gene Ontology (GO) has become a well accepted standard in organizing gene function categories. Different gene function categories in GO can have very sophisticated relationships, such as 'part of' and 'overlapping'. Until now, no clustering algorithm can generate gene clusters within which the relationships can naturally reflect those of gene function categories in the GO hierarchy. The failure in resembling the relationships may reduce the confidence of clustering in gene function prediction. In this paper, we present a new clustering technique, Smart Hierarchical Tendency Preserving clustering (SHTP-clustering), based on a bicluster model, Tendency Preserving cluster (TP-Cluster). By directly incorporating Gene Ontology information into the clustering process, the SHTP-clustering algorithm yields a TP-cluster tree within which any subtree can be well mapped to a part of the GO hierarchy. Our experiments on yeast cell cycle data demonstrate that this method is efficient and effective in generating the biological relevant TP-Clusters.

Algorithms↗

PubMed2003

The abnormalities of chromosome 8 in two hepatocellular carcinoma cell clones with the same genetic background and different metastatic potential.

PURPOSE: Two hepatocellular carcinoma (HCC) cell clones named MHCC97-H and MHCC97-L with different metastatic potential have recently been established from the same parent cell line MHCC97 in our institute. The cytogenetic alterations of these two clones were investigated in this study to explore the possible clues to the mechanism involved in HCC metastasis. METHODS: Their chromosomal aberrations were analyzed with comparative genomic hybridization (CGH), chromosome-specific painting, and two-color fluorescence in situ hybridization (FISH). RESULTS: The aberrations were found in a total of 17 chromosomes, and six kinds of the aberrations including gains of 1q, 7q, 8q, 20, and the losses of 8p23, 21q were found both in the two cell clones and their parent cell line MHCC97. Using modified CGH, with the DNA of MHCC97-L as control to test the MHCC97-H clone, the loss of 8p23 and the gain of 1q31-32, 8q21.3-22, 13q22, 17q22 were highlighted, and the most significant finding was on chromosome 8. Dual color FISH combining a pericentromeric probe and a BAC probe mapping at 8q23.1 was then performed to verify this result, and the signal ratios of the BAC to centromere were 1.43 in MHCC97-H and 1.45 in MHCC97-L, confirming the over-representations at 8q in both cells. Another interesting finding in the dual-color metaphase FISH was the intrachromosomal translocation of 8q to 8p (looked like an isochromosome 8) and non-reciprocal translocation of part of 8q to 4q, which was further clarified and proved by the FISH with whole chromosome 8 painting probe. CONCLUSIONS: The high copies amplification on 8q, the formation of isochromosome 8, non-reciprocal translocation of partial 8q to 4q, and loss of 8p occurred at the same time and are the characteristic chromosomal aberrations of the two cell clones. The chromosome 8p, especially 8p23, might harbor some novel genes related to the HCC metastasis.

Carcinoma, Hepatocellular↗

PubMed2003

Divergent regioselectivity in the base-promoted reactions of cyclic eight-membered alpha-ketols with activated halides.

[reaction: see text] Deprotonation of 2-hydroxycyclooctanone followed by exposure to an allylic or benzylic halide proceeds very selectively to give the product of C-alkylation. The effect of Delta(5,6)-unsaturation is to promote instead the formation of the O-alkylated derivative. This crossover in kinetic preference is attributed to an inability of the olefinic system to attain a conformation conducive to proton abstraction at C-2.

Journal Article↗

PubMed2003

Concise total syntheses of the bioactive mesotricyclic diterpenoids jatrophatrione and citlalitrione.

The highly functionalized [5.9.5] tricyclic framework resident in jatrophatrione (1) and citlalitrione (2) has been synthesized. The route begins with the tandem anionic oxy-Cope rearrangement/methylation/transannular ene cyclization of 21 and subsequent introduction of a conjugated enone double bond. Hydroxyl-directed 1,4-reduction of this functionality in 25 with LiAlH(4)/CuI/hexamethylphosphoramide/tetrahydrofuran sets the stage for the implementation of a Grob fragmentation and expedited generation of 27. Stereocontrolled intramolecular hydrosilylation allows for the subsequent introduction of a cyclic carbonate as in 53. This intermediate undergoes remarkably efficient, fully regiocontrolled Treibs reaction to generate 54, with this maneuver serving as a pivotal step for making 1 available five steps later. Treatment of 1 with m-chloroperbenzoic acid leads to 2, with attack occurring preferentially on a alpha-face of the double bond more remote to the carbonyl.

Antineoplastic Agents, Phytogenic↗

PubMed2003

The microcell mediated transfer of human chromosome 8 into highly metastatic rat liver cancer cell line C5F.

AIM: Our previous research on the surgical samples of primary liver cancer with CGH showed that the loss of human chromosome 8p had correlation with the metastatic phenotype of liver cancer. In order to seek the functional evidence that there could be a metastatsis suppressor gene(s) for liver cancer on human chromosome 8, we tried to transfer normal human chromosome 8 into rat liver cancer cell line C5F, which had high metastatic potential to lung. METHODS: Human chromosome 8 randomly marked with neo gene was introduced into C5F cell line by MMCT and positive microcell hybrids were screened by double selections of G418 and HAT. Single cell isolation cloning was applied to clone microcell hybrids. Finally, STS-PCR and WCP-FISH were used to confirm the introduction. RESULTS: Microcell hybrids resistant to HAT and G418 were obtained and 15 clones were obtained by single-cell isolation cloning. STS-PCR and WCP-FISH proved that human chromosome 8 had been successfully introduced into rat liver cancer cell line C5F. STS-PCR detected a random loss in the chromosome introduced and WCP-FISH found a consistent recombination of the introduced human chromosome with the rat chromosome. CONCLUSION: The successful introduction of human chromosome 8 into highly metastatic rat liver cancer cell line builds the basis for seeking functional evidence of a metastasis suppressor gene for liver cancer harboring on human chromosome 8 and its subsequent cloning.

Animals↗

PubMed2003

The effect of theophylline on sleep-disordered breathing in patients with stable chronic congestive heart failure.

OBJECTIVE: To determine the prevalence of sleep-disordered breathing in patients with stable, optimally treated chronic congestive heart failure and the effect of short-term oral theophylline therapy on periodic breathing in these patients. METHODS: Patients with stable, optimally treated chronic congestive heart failure were monitored by polysomnography during nocturnal sleep. The effects of theophylline therapy on periodic breathing associated with stable heart failure were observed before and after treatment. RESULTS: Patients were divided into two groups. Group I (n = 21) consisted of individuals with 15 episodes of apnea and hypopnea [as determined by the apnea-hypopnea index (AHI)] per hour or less; Group II (n = 15, 41.7%) individuals had an index of more than 15 episodes per hour. In group II, the AHI varied from 16.8 to 78.8 (42.6 +/- 15.5) in which the obstructive AHI was 11.1 +/- 8.4 and the central AHI was 31.5 +/- 9.6. Group II had significantly more arousals (36.8 +/- 21.3 compared with 19.4 +/- 11.2 in group I) that were directly attributable to episodes of apnea and hypopnea, lower arterial oxyhemoglobin saturation (76.7% +/- 4.6% compared with 86.5% +/- 2.8%) and lower left ventricular ejection fraction (24.2% +/- 8.8% compared with 31.5% +/- 10.6%). Thirteen patients with compensated heart failure and periodic breathing received theophylline orally (at an average dose of 4.3 mg/kg) for five to seven days. After treatment, the mean plasma theophylline concentration was (11.3 +/- 2.5) micro g/ml. Theophylline therapy resulted in significant decreases in the number of AHI (20.8 +/- 13.2 vs. 42.6 +/- 15.5; P < 0.001) and the number of episodes of central apnea-hypopnea per hour (10.1 +/- 7.6 vs. 31.5 +/- 9.6; P < 0.001). Furthermore, the percentage of total sleep time during which arterial oxyhemoglobin saturation (SaO(2)) was less than 90 percent (8.8% +/- 8.6% vs. 23.4% +/- 24.1%; P < 0.05) and the arousals per hour (18.7 +/- 21.2 vs. 36.8 +/- 21.3; P < 0.05) were also lower. There were no significant differences in the characteristics of sleep or obstructive AHI before and after theophylline treatment. CONCLUSIONS: The prevalence of sleep-disordered breathing (mainly periodic respiration or cheyne-stokes respiration with central sleep apnea) is high in patients with stable chronic congestive heart failure. The sleep-disordered breathing episodes are associated with severe nocturnal arterial blood oxyhemoglobin desaturation and excessive arousals. In these patients, oral theophylline therapy may reduce the number of episodes of central apnea and hypopnea and the duration of arterial oxyhemoglobin desaturation during nocturnal sleep.

Aged↗

PubMed2003

Discovering compact and highly discriminative features or feature combinations of drug activities using support vector machines.

Nowadays, high throughput experimental techniques make it feasible to examine and collect massive data at the molecular level. These data, typically mapped to a very high dimensional feature space, carry rich information about functionalities of certain chemical or biological entities and can be used to infer valuable knowledge for the purposes of classification and prediction. Typically, a small number of features or feature combinations may play determinant roles in functional discrimination. The identification of such features or feature combinations is of great importance. In this paper, we study the problem of discovering compact and highly discriminative features or feature combinations from a rich feature collection. We employ the support vector machine as the classification means and aim at finding compact feature combinations. Comparing to previous methods on feature selection, which identify features solely based on their individual roles in the classification, our method is able to identify minimal feature combinations that ultimately have determinant roles in a systematic fashion. Experimental study on drug activity data shows that our method can discover descriptors that are not necessarily significant individually but are most significant collectively.

Algorithms↗

PubMed2002

Concerning the antileukemic agent jatrophatrione: the first total synthesis of a [5.9.5] tricyclic diterpene.

The highly functionalized [5.9.5] tricyclic framework resident in jatrophatrione (1) has been synthesized. The route begins with the tandem anionic oxy-Cope rearrangement/methylation/transannular ene cyclization of 5 and subsequent introduction of a conjugated enone double bond. Hydroxyl-directed 1,4-reduction of this functionality in 6 with LiAlH4/CuI/HMPA/THF sets the stage for the implementation of a Grob fragmentation and rapid generation of 8. Stereocontrolled intramolecular hydrosilylation allows for the subsequent introduction of a cyclic carbonate as in 11. This intermediate undergoes a remarkably smooth Treibs reaction to generate 12, thus serving as a pivotal step for making 1 available five steps later.

Antineoplastic Agents, Phytogenic↗

PubMed2002

[Establishment of human hepatocellular carcinoma cell line with spontaneous pulmonary metastasis through in vivo selection].

OBJECTIVE: To establish a hepatocellular carcinoma (HCC) cell line from lung metastatic lesions of human HCC in nude mice so as to provide suitable model for the study of lung-metastasis-related molecular mechanisms. METHODS: HCC clone cells MHCC97-H were inoculated subcutaneously into nude mice. The pulmonary metastatic lesions were harvested from the moribund animals and then re-implanted into the nude mice for the second round of selection. The same procedure was repeated twice. New cell line from the third round of lung metastasis was thus established and the following parameters were studied: morphology, in vitro growth curve, plate efficiency, migration, karyotype, flow cytometry, immunocytochemistry for AFP, albumin and cytokeratin 8 (CK8), flourescent PCR for HBV DNA, tumorigenicity and spontaneous metastasis via subcutaneous injection and orthotopic implantation of tumor tissue. RESULTS: The cell line established from nude mouse lung metastasis was designated as HCCLM3, consisting of polygonal epithelial cells with hypotriploid karyotype, its main range of chromosome being 55 - 58. The cell population doubling time was 34.9 hours, plate efficiency 32.4 +/- 3.2%, and cell migration rate 20 +/- 2 microm/h. The cells were positive for AFP, albumin, CK8, and P16 and negative for P53, nm23 and HBsAg. Fluorescent PCR showed HBV DNA integration into cellular genome. When 5 x 10(6) cells were injected subcutaneously into nude mice, the tumorigenicity was 100% with a latency period of 11 +/- 1 d. Five weeks after subcutaneous injection, the pulmonary metastatic rate was 100%, the median number of lung metastases being 121 per mouse. After orthotopic implantation of tumor tissue into nude mouse liver for 35 d, wide spread regional and distant metastases occurred, the metastatic rate was 100% for abdominal wall, 80% for organs in abdominal cavity, 100% for liver, 70% for diaphragm, and 100% for lung. The median number of lung metastatic lesions was 268 per mouse. CONCLUSION: A new HCC cell line has been established, which is characterized by high pulmonary metastasis via both subcutaneous and orthotopic inoculation. It provides a new model for the study of liver cancer metastasis.

Animals↗

PubMed2002

Effects of theophylline on CD4+ T lymphocyte, interleukin-5, and interferon gamma in induced sputum of asthmatic subjects.

AIM: To investigate the mechanism of anti-inflammatory action of theophylline on asthma. METHODS: Nineteen asthmatic subjects were administered 200 mg sustained-release theophylline twice daily for 4 weeks. The number of CD4+ T lymphocytes, eosinophils, and the levels of interleukin (IL)-5 and interferon gamma (IFN-gamma) in sputum pre- and post-administration were measured by direct immunofluorescene technique, Wright's stain and enzyme-linked immunosorbent assay, respectively. The symptom scores and lung function were also evaluated. RESULTS: Theophylline treatment significantly improved symptom scores and FEV1.0, FEV1.0 % (P < 0.05) and reduced sputum eosinophils (P < 0.01) in asthmatic subjects. These were accompanied by a decrease in sputum IL-5 level (P < 0.01), but sputum CD4+ T lymphocytes and IFN-gamma had no significant change (P >0.05). The mean (range) serum theophylline concentration in final steady state was 7.9 (3.9 - 12.9) mg/L. CONCLUSION: The anti-inflammatory action of theophylline in asthma may result from reduction of IL-5 production in the airways.

Adult↗

PubMed2002

Towards automatic clustering of protein sequences.

Analyzing protein sequence data becomes increasingly important recently. Most previous work on this area has mainly focused on building classification models. In this paper, we investigate in the problem of automatic clustering of unlabeled protein sequences. As a widely recognized technique in statistics and computer science, clustering has been proven very useful in detecting unknown object categories and revealing hidden correlations among objects. One difficulty that prevents clustering from being performed directly on protein sequence is the lack of an effective similarity measure that can be computed efficiently. Therefore, we propose a novel model for protein sequence cluster by exploring significant statistical properties possessed by the sequences. The concept of imprecise probabilities are introduced to the original probabilistic suffix tree to monitor the convergence of the empirical measurement and to guide the clustering process. It has been demonstrated that the proposed method can successfully discover meaningful families without the necessity of learning models of different families from pre-labeled "training data".

Algorithms↗

PubMed2002

Accelerating approximate subsequence search on large protein sequence databases.

Bioinformatics has become an active research area in recent years. The amount of mapped sequences doubles every fourteen months. BLAST has been widely employed for retrieving sequences which has similar portion(s) to a given sequence. However, BLAST has to scan the entire database every time when a query is issued. This can be very time consuming especially when the database is large. In this paper, we study the problem on how to build a persistent index structure for protein sequences to support approximate match. The suffix tree has been proposed as a solution to index sequence database and has been deployed on organizing DNA sequences (Hunt et al. 2001). Unfortunately, it suffers from the problem of "memory bottleneck" that prevents it from being applied efficiently to a large database. The performance even degrades further for protein database due to a larger fanout at each node. Here, we employ an indexing structure, called BASS-tree, to support approximate match in sublinear time on a large protein database. We call this indexing method as sequence approximate match (SAM) index method. The search of approximate matches can be properly directed to the portion in the database with a high potential of matching quickly. It has been demonstrated in our experiments that the potential performance improvement is in an order of magnitude over alternative methods such as the BLAST algorithm and the suffix tree.

Algorithms↗