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Biomedical subjects

C Jin

Publications and source records attributed to C Jin.

At least 19 recordsLinked to original sources

Biological activities of a novel selective oestrogen receptor modulator derived from raloxifene (Y134).

BACKGROUND AND PURPOSE: Selective oestrogen receptor (ER) modulators (SERMs) are of great value in the treatment of breast cancer and osteoporosis. The aim of this study was to characterize pharmacologically a new class of SERMs synthesized based on the core structure of raloxifene. EXPERIMENTAL APPROACH: Competitive receptor binding and luciferase-based reporter methods were used to study the bioactivities of raloxifene analogues, followed by efficacy determination in breast cancer cell proliferation assay. ER antagonist effects were investigated in female rats by measuring uterine and mammary gland growth, using wet weight, BrdU incorporation and terminal end bud (TEB) as indicators. KEY RESULTS: Five analogues, belonging to two different structural series and display higher binding affinities for ERalpha than ERbeta were functionally evaluated. One such analogue, Y134, exhibited potent antagonist activity at ERs in CV-1 cells cotransfected with plasmids containing ERalpha or ERbeta and oestrogen-response element-driven luciferase. The estimated IC(50) value was 0.52 nM for ERalpha and 2.94 nM for ERbeta, comparable to that of raloxifene. Little cytotoxicity was observed at Y134 concentrations below 10 microM. Y134 suppressed oestrogen-stimulated proliferation of ER-positive human breast cancer MCF-7 and T47D cells. At an identical dose, administered to ovariectomized rats, Y134 was more effective than raloxifene at arresting oestrogen-induced outgrowth of TEB and mammary gland DNA synthesis, but their inhibitory effects on the uterus were comparable. CONCLUSIONS AND IMPLICATIONS: Y134 is a potent ER antagonist with better mammary gland selectivity than raloxifene and shows potential for development as a new SERM for therapeutic use.

Animals↗

Hypoxia-inducible factor 1alpha cDNA cloning and its mRNA and protein tissue specific expression in domestic yak (Bos grunniens) from Qinghai-Tibetan plateau.

Adaptation to hypoxia is regulated by hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor consisting of an oxygen-regulated alpha-subunit and a constitutively expressed beta-subunit. How animals living on Qinghai-Tibetan plateau adapt to the extreme hypoxia environment is known indistinctly. In this study, the Qinghai yak, which has been living at 3000-5000 m altitude for at least two millions of years, was selected as the model of high hypoxia-tolerant adaptation species. The HIF-1alpha ORFs (open reading frames) encoding for two isoforms of HIF-1alpha have been cloned from the brain of the domestic yak. Its expression of HIF-1alpha was analyzed at both mRNA and protein levels in various tissues. Both its HIF-1alpha mRNA and protein are tissue specific expression. Its HIF-1alpha protein's high expression in the brain, lung, and kidney showed us that HIF-1alpha protein may play an important role in the adaptation to hypoxia environment.

Amino Acid Sequence↗

Two photon induced polymerization of organic-inorganic hybrid biomaterials for microstructured medical devices.

Three-dimensional microstructured medical devices, including microneedles and tissue engineering scaffolds, were fabricated by two photon induced polymerization of Ormocer organic-inorganic hybrid materials. Femtosecond laser pulses from a titanium:sapphire laser were used to break chemical bonds on Irgacure 369 photoinitiator within a small focal volume. The radicalized starter molecules reacted with Ormocer US-S4 monomers to create radicalized polymolecules. The desired structures are fabricated by moving the laser focus in three dimensions using a galvano-scanner and a micropositioning system. Ormocer surfaces fabricated using two photon induced polymerization demonstrated acceptable cell viability and cell growth profiles against B35 neuroblast-like cells and HT1080 epithelial-like cells. Lego-like interlocking tissue engineering scaffolds and microneedle arrays with unique geometries were created using two photon induced polymerization. These results suggest that two photon induced polymerization is able to create medical microdevices with a larger range of sizes, shapes, and materials than chemical isotropic etching, injection molding, reactive ion etching, surface micromachining, bulk micromachining, polysilicon micromolding, lithography-electroforming-replication, or other conventional microfabrication techniques.

Animals↗

The effect of saliva or serum on bacterial and Candida albicans colonization on type I collagen.

Colonization of Candida albicans on oral surfaces can serve as a reservoir for disseminated infections, such as aspiration pneumonia and gastrointestinal infection, particularly in the immunocompromised host. Therefore, the aim of this study was to investigate the effects of salivary and serum pellicles on C. albicans, Streptococcus mutans, S. sanguis, Lactobacillus and Actinomyces colonization on type I collagen, a major organic component of periodontal ligaments. The colonization potential of two isolates each of C. albicans, S. mutans and S. sanguis, and a single isolate each of Lactobacillus and Actinomyces to uncoated (control), saliva-coated or serum-coated type I collagen plates (surface area 143 mm(2), Cell Disk; Sumitomo, Tokyo, Japan) was examined using a bioluminescent adenosine triphosphate assay based on firefly luciferase-luciferin system. The results revealed that with mutans streptococci, a saliva pellicle was significantly more effective in promoting bacterial colonization compared with the pellicle-free collagen disc, and the serum-coated sample significantly inhibited the colonization of streptococci (anova; P < 0b01). In contrast, in the case of C. albicans, Lactobacillus and Actinomyces isolates, a serum pellicle was significantly more effective in promoting the colonization, followed by saliva pellicle and uncoated specimen (anova; P < 0b01). These results suggested that crevicular fluid rich in seruminous components would promote the colonization of Candida, Lactobacillus and Actinomyces on type I collagen as opposed to streptococci which showed greater avidity to saliva-coated collagen.

Actinomyces↗

Molecular cytogenetic characterization of the 11q13 amplicon in head and neck squamous cell carcinoma.

Amplification of 11q13 DNA sequences and overexpression of CCND1 are common findings in head and neck squamous cell carcinoma (HNSCC), identified in about 30% of the cases. However, little is known about initiation of the amplification and the organization of the amplicon. In order to study the structure of the amplicon in more detail and to learn more about the mechanisms involved in its initiation, prometaphase, metaphase, and anaphase fluorescence in situ hybridization (FISH) with 40 BAC clones spanning a 16-Mb region in chromosome bands 11q12.2 to 11q13.5 was performed in nine HNSCC cell lines with homogeneously staining regions. FISH analysis showed that the size of the amplicon varied among the nine cell lines, the smallest being 2.12 Mb and the largest 8.97 Mb. The smallest overlapping region of amplification was approximately 1.61 Mb, covering the region from BAC 729E14 to BAC 102B19. This region contained several genes previously shown to be amplified and overexpressed in HNSCC, including CCDN1, CTTN, SHANK2, and ORAOV1. The cell lines were also used to study the internal structure of the amplicon. Various patterns of amplified DNA sequences within the amplicon were found among the nine cell lines. Even within the same cell line, different amplicon structures could be found in different cell populations, indicating that the mechanisms involved in the development of the amplicons in HNSCC were more complex than previously assumed. The frequent finding of inverted repeats within the amplicons, however, suggests that breakage-fusion-bridge cycles are important in the initiation, but the fact that such repeats constituted only small parts of the amplicons indicate that they are further rearranged during tumor progression.

Anaphase↗

Amplification and overexpression of aurora kinase A (AURKA) in immortalized human ovarian epithelial (HOSE) cells.

Immortalization is an early and essential step of human carcinogenesis. Amplification of chromosome 20q has been shown to be a common event in immortalized cells and cancers. We have previously reported that gain and amplification of chromosome 20q is a non-random and common event in immortalized human ovarian surface epithelial (HOSE) cells. The chromosome 20q harbors genes including TGIF2 (20q11.2-q12), AIB1 (20q12), PTPN1 (20q13.1), ZNF217 (20q13.2), and AURKA (20q13.2-q13.3), which were previously reported to be amplified and overexpressed in ovarian cancers. Some of these genes may be involved in immortalization of HOSE cells and represent crucial premalignant changes in ovarian surface epithelium. Investigation of the involvement of these genes was examined in four pairs of pre-crisis (preimmortalized) and post-crisis (immortalized) HOSE cells. Overexpression of AURKA (Aurora kinase A), also known as BTAK and STK15, by both real time-quantitative polymerase chain reaction (RT-QPCR) and Western blotting was detected in all the four immortalized HOSE cells examined while overexpression of AIB1 and ZNF217 was observed in two of four immortalized HOSE cells examined. Overexpression of TGIF2 and PTPN1 was not significant in our immortalized HOSE cell systems. The degree of overexpression of AURKA was shown to be closely associated with the amplification of chromosome 20q in immortalized HOSE cells. Fluorescence in situ hybridization (FISH) with labeled P1 artificial clone (PAC) confirmed the amplification of the chromosomal region (20q13.2-13.3) where AURKA resides. DNA amplification of AURKA was also confirmed using semi-quantitative PCR. Our study showed that amplification and overexpression of AURKA is a common and significant event during immortalization of HOSE cells and may represent an important premalignant change in ovarian carcinogenesis.

Aurora Kinase A↗

Suppressive effects of nitric oxide production and inducible nitric oxide synthase (iNOS) gene expression by Calystegia soldanella methanol extract on lipopolysaccharide-activated RAW 264.7 cells.

Since nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) has been found to be involved in various pathophysiological processes, including inflammation and carcinogenesis, the modulators of NO synthesis or expression have been considered as potential anti-inflammatory and cancer chemopreventive agents. In this study, to procure the iNOS inhibitors from natural products, we evaluated 57 methanol extracts of natural products including Korean indigenous plants for the inhibition of NO formation on lipopolysaccharide (LPS)-activated mouse macrophage-like RAW 264.7 cells. As a result, several extracts including those from Actinodaphne lancifolia, Calystegia soldanella, Caryratia japonica, Citrus dachibana, Dystaenia takeshimana, Erysimum aurantiacum, Hovenia undulata, Stewartia koreana and Viburnum awabuki showed potent inhibitory activities of NO production (>70% inhibition at the test concentration of 40 microg/ml). In particular, the extract of Calystegia soldanella showed a potential inhibition of NO production in a dose-dependent manner (IC50=4.3 microg/ml). Subsequent study also exhibited that the extract of Calystegia soldanella significantly suppressed iNOS protein and gene expression in a dose-dependent manner. These results suggest that Calystegia soldanella might be a new potential candidate for developing an iNOS inhibitor from natural products and also could be warranted for further elucidation of active principles for the development of new anti-inflammatory and/or cancer chemopreventive agents.

Animals↗

Proximal versus distal hyperplastic polyps of the colorectum: different lesions or a biological spectrum?

BACKGROUND: Because of their suggested link with microsatellite instability high colorectal cancers, right sided hyperplastic polyps (HPs) may differ from their distally located counterparts. This is highlighted by the recognition of a variant HP, termed sessile serrated adenoma (SSA), which predominates in the proximal colon. HPs displaying the morphological features now associated with SSAs have been shown to have altered expression of "cancer associated" markers, but no studies have investigated whether this is dependent on anatomical location of the polyps. AIMS: To evaluate morphological and functional features in right versus left sided HPs from patients without colorectal cancer with the aim of identifying distinguishing characteristics. METHODS: HPs originating in the proximal and distal colorectum were histochemically and immunohistochemically stained to evaluate a panel of markers related to proliferation and differentiation. In addition, a series of morphological features was evaluated for each polyp. RESULTS: Crypt serration, crypt dilatation, and horizontal crypt growth were more common among HPs from the right side, whereas histochemical factors including mucin changes, global methylation status, and expression of carcinoembryonic antigen were not significantly different. An age disparity was also seen between patients with right versus left sided lesions, with patients with right sided lesions being an average of more than 10 years younger than those with left sided lesions. CONCLUSIONS: These findings suggest that right and left sided HPs differ mainly in terms of growth regulation rather than cellular differentiation, implying that these lesions belong to a continuous spectrum of serrated polyps that differ quantitatively rather than qualitatively.

Age Factors↗

Changes in surface roughness and colour stability of soft denture lining materials caused by denture cleansers.

Soft denture lining materials were immersed into solutions of denture cleansers for 8 h at room temperature, and immersed into distilled water for the remainder of the 24-h period at 37 degrees C. Surface roughness of the soft denture lining materials was measured by contact type surface roughness instrument. For the colour stability test, soft denture lining materials were immersed in the denture cleansers as described above for 180 days. Finally, the colour changes of each material were quantitatively measured by a photometrical instrument to obtain the colour differences between newly processed specimen and immersed specimens (P < 0.01). An autopolymerizing silicone material, Evatouch, exhibited severe changes in surface roughness by all denture cleanser, and the generic material GC Denture Relining showed the minimal changes. Severe colour changes were also observed with some liner and cleanser combinations (P < 0.01). Except for Evatouth, the four silicone soft liners were more stable in surface roughness and in colour change than the two acrylic soft liners. One autopolymerizing silicone (GC denture relining) and one heat curing silicone (Molloplast B) demonstrated the best stability.

Color↗

Biofilm formation of Candida albicans on the surfaces of deteriorated soft denture lining materials caused by denture cleansers in vitro.

Candidal colonization and subsequent biofilm formation on denture materials are important in the development of pathogenesis, such as denture stomatitis. Routine use of denture cleansers is one of the most effective methods of denture plaque control, although the incompatibility of soft liners and denture cleansers cause damage to the materials. The present study, biofilm formation of Candida albicans on the surfaces of soft denture lining materials, immersed in denture cleansers for 180 days were studied. Seven commercially available soft denture lining materials, were artificially deteriorated by immersion into three commercially available denture cleansers for 180 days, and subsequent fungal growth and biofilm formation were studied by measuring pH of the media and by the use of adenosine triphosphate (ATP) analysis. Fungal biofilm formation on the deteriorated soft liners varied depending upon the combination of the soft liners and denture cleansers. Several combinations of soft liners with denture cleansers exhibited the significantly high colonization capacity as compared with each sample immersed in distilled water, used as individual controls. The relationship between the biofilm formation on the samples of each material and the surface roughness of the soft lining materials was analyzed. However, no significant correlation was observed. The results, taken together, suggested that fungal colonization could be predominantly regulated by the combination of lining material with denture cleansers. In clinical terms, our findings suggests that daily cleansing of soft lining materials with mismatched denture cleansers promoted the subsequent biofilm formation of fungi on the materials.

Biofilms↗

Role of self-assembled gold nanodots in improving the electrical and optical characteristics of zinc oxide films.

We have studied the effect of embedding nanocrystalline Au particles on the electrical and optical characteristics of ZnO films. Au-embedded epitaxial ZnO films were deposited on (0001) sapphire substrates with a pulsed laser deposition technique. The crystalline quality of both the ZnO matrix and Au nanoparticles was investigated by X-ray diffraction and transmission electron microscopy. Composite films were characterized by photoluminescence, optical absorption, and low-temperature electrical resistivity measurements. Photoluminescence spectra of theses films showed a sharp excitonic peak at 3.22 +/- 0.05 eV without any signature of green band emission. Electrical resistivity measurements showed these films to be highly conducting, with a room-temperature resistivity of 3.4 +/- 0.2 m omega-cm.

Crystallization↗

Centrosomal abnormalities, multipolar mitoses, and chromosomal instability in head and neck tumours with dysfunctional telomeres.

Carcinomas of the head and neck typically exhibit complex chromosome aberrations but the underlying mutational mechanisms remain obscure. Evaluation of cell division dynamics in low-passage cell lines from three benign and five malignant head and neck tumours revealed a strong positive correlation between multipolarity of the mitotic spindle and the formation of bridges at anaphase in both benign and malignant tumours. Cells exhibiting a high rate of mitotic abnormalities also showed several chromosome termini lacking TTAGGG repeats and a high frequency of dicentric chromosomes. Multicolour karyotyping demonstrated a preferential involvement in structural rearrangements of chromosomes with deficient telomeres. The majority of malignant, mitotically unstable tumours expressed the reverse transcriptase subunit of telomerase. These data indicate that some of the genomic instability in head and neck tumours is initiated by telomere dysfunction, leading to the formation of dicentric chromosomes. These form chromosome bridges at mitosis that could prevent the normal anaphase-telophase transition. In turn, this may cause an accumulation of centrosomes and mitotic multipolarity. Telomerase expression does not confer total stability to the tumour genome but could be crucial for moderating the rate of chromosomal evolution.

Adenoma, Pleomorphic↗

Synthesis and binding affinities of 2 beta-(3-iodoallyloxycarbonyl)-3 beta-(4-substituted-aryl)tropane analogues as ligands for the dopamine transporter studies.

Tropane analogues from cocaine, which is known to be one of the most reinforcing and addictive compounds, were designed, synthesized, and characterized for inhibition of presynaptic uptake of dopamine (DA) in brain. Eight new derivatives of 3 beta-aryl-2 beta-(3-iodoallyloxycarbonyl)tropanes were synthesized and tested for their potential abilities to displace [(3)H]2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (WIN 35,428) binding to the rat striatal membranes.

Animals↗

Cytogenetic and fluorescence in situ hybridization characterization of chromosome 8 rearrangements in head and neck squamous cell carcinomas.

Structural rearrangements of chromosome 8 are frequently encountered in squamous cell carcinomas of the head and neck (HNSCC). These aberrations often affect the centromeric region, resulting in the formation of isochromosome i(8q) and whole arm translocations. Some tumors may display structural rearrangements of 8p23. To characterize further the localization of the breakpoints in such rearrangements, 12 HNSCC known to carry pericentromeric rearrangements of chromosome 8 and 8p23 abnormalities were investigated with fluorescence in situ hybridization (FISH) by the use of 15 YAC clones spanning 8p23 and 8p11 to 8q11. FISH confirmed that all, except one, aberrations cytogenetically interpreted to be i(8q) were true, monocentric i(8q). Similarly, all whole-arm translocations appeared as centric fusions. It could thus be concluded that the essential outcome of these rearrangements is genomic imbalances and not rearrangement of genes in the pericentromeric region. By the use of five YAC clones mapping to 8p23, different breakpoints at the molecular level were disclosed in cases with cytogenetically identical 8p23 rearrangements. An evaluation of the genomic imbalances detected in the present series revealed that overrepresentation of 8q material was present in 11 of the 12 tumors. The most commonly gained segment was 8q22 approximately qter, found in all cases with 8q overrepresentation. Loss of parts of or the entire 8p was seen in 10 tumors. The smallest overlapping deleted region was localized to the subtelomeric region of 8p.

Aged↗

[Electric pulse mediated high efficient gene transfer].

OBJECTIVE: To study gene transfer mediated by electric pulse and optimize the parameters of electric pulse in vivo. METHODS: 10 micrograms plasmid pcD2/LacZ was injected into the quadriceps of 220 Kunming mice. One to two minutes after the DNA injection electric pulse with different parameters was given to the injection site. Three days after, activity of beta-galactosidase was measured, and the expression of Laz2 gene in muscle was determined by histochemical staining. RESULTS: The activity of beta-galactosidase in electric pulse group (131.6 U/mg +/- 86.6 U/mg protein) was 30 fold higher than that in direct injection group (4.9 U/mg +/- 1.0 U/mg protein) (P < 0.05). Histochemical analysis of muscles injected with a LacZ expression plasmid also showed that in vivo electric pulse increased both the number of positively stained muscle fibers and the density of staining. When the electric pulse was with the parameters of 200 V/cm, 40 ms, 6 pulses and 1HZ, maximal gene expression was achieved. CONCLUSION: Electric pulse, with optimal parameters, increases gene expression. Electric pulse makes much more gene expression than mere intramuscular DNA injection.

Animals↗

A rare premalignant prostate tumor epithelial cell syndecan-1 forms a fibroblast growth factor-binding complex with progression-promoting ectopic fibroblast growth factor receptor 1.

The abnormal appearance and age-dependent loss of resident fibroblast growth factor receptor-2 (FGFR2) and gain of activity of FGFR1 in epithelial cells is a hallmark of the slow progression to malignancy in some models of prostate cancer. Pericellular matrix heparan sulfate (HS) is an integral subunit of the FGFR tyrosine kinase complex that restricts activity in absence of FGF, facilitates binding of an activating FGF, and confers specificity for FGF isoforms. In this report, we isolated and purified HS proteoglycan (HSPG) from premalignant prostate tumor epithelial cells based on the ability of the HS chains to form a binary complex with immunoglobulin module II of the ectopic and progression-promoting FGFR1 that was competent to bind FGF. The FGFR1 affinity-purified product exhibited a specific activity of over 600 times that of crude cellular HSPG enriched from cell lysates by ion exchange chromatography. The purified preparation exhibited a single NH(2)-terminal sequence with 11 of 13 residues identical to syndecan-1. The activity of purified recombinant glutathione S-transferase-tagged syndecan-1 expressed in premalignant epithelial cells confirmed that syndecan-1 bears HS chains that exhibit the rare motif that forms the FGF-binding complex with ectopic FGFR1. These results are the first to identify by affinity purification a specific HSPG core protein, the HS chains of which act as an integral subunit of the FGFR complex. The results suggest that syndecan-1 provides HS chains in premalignant epithelial cells to both the FGFR2- and FGFR1-signaling complexes that are integral to their dual roles in progression to malignancy.

Amino Acid Sequence↗