Biomedical subjects

Bing Su

Publications and source records attributed to Bing Su.

51 records · Page 3Linked to original sources

PubMed2004

Analyses of genetic structure of Tibeto-Burman populations reveals sex-biased admixture in southern Tibeto-Burmans.

An unequal contribution of male and female lineages from parental populations to admixed ones is not uncommon in the American continents, as a consequence of directional gene flow from European men into African and Hispanic Americans in the past several centuries. However, little is known about sex-biased admixture in East Asia, where substantial migrations are recorded. Tibeto-Burman (TB) populations were historically derived from ancient tribes of northwestern China and subsequently moved to the south, where they admixed with the southern natives during the past 2600 years. They are currently extensively distributed in China and Southeast Asia. In this study, we analyze the variations of 965 Y chromosomes and 754 mtDNAs in >20 TB populations from China. By examining the haplotype group distributions of Y-chromosome and mtDNA markers and their principal components, we show that the genetic structure of the extant southern Tibeto-Burman (STB) populations were primarily formed by two parental groups: northern immigrants and native southerners. Furthermore, the admixture has a bias between male and female lineages, with a stronger influence of northern immigrants on the male lineages (approximately 62%) and with the southern natives contributing more extensively to the female lineages (approximately 56%) in the extant STBs. This is the first genetic evidence revealing sex-biased admixture in STB populations, which has genetic, historical, and anthropological implications.

Chromosomes, Human, Y↗

PubMed2004

Hypermethylation of the RASSF1A gene in gliomas.

BACKGROUND: Promoter methylation is an important pathway in transcriptional silencing of tumor suppressor genes (TSGs) in brain tumors. The identified 3p21.3 tumor suppressor gene RAS association domain family protein 1A (RASSF1A) is highly methylated in primary lung, breast and other tumors. We investigated the promoter methylation and gene expression of RASSF1A in gliomas. METHODS: The methylation status of the promoter region of RASSF1A, p16INK4A and death-associated protein kinase (DAPK) genes was analyzed by methylation-specific PCR (MSP) in 41 surgically resected gliomas. RASSF1A expression was also detected by reverse-transcription polymerase chain reaction (RT-PCR) in 28 glioma tissues. RESULTS: The frequencies of RASSF1A, p16INK4A and DAPK promoter methylation were 13/41 (31.7%), 3/41 (7.3%) and 6/41 (14.6%) respectively. However, the methylations of those genes were not correlated with the clinical characteristics of patients (tumor grade, tumor types and sex). Among 28 glioma tissues, 6 showed the loss of the gene (21.4%). Promoter hypermethylation of RASSF1A is associated with loss of gene expression in glioma tissues. (p=0.022). CONCLUSIONS: Our results suggested that the RASSF1A gene might play an important role in glioma carcinogenesis. It also gives us an insight for future glioma medical therapy with a demethylating agent.

Adolescent↗

PubMed2004

Construction, characterization and chromosomal mapping of bacterial artificial chromosome (BAC) library of Yunnan snub-nosed monkey (Rhinopithecus bieti).

We constructed a high redundancy bacterial artificial chromosome library of a seriously endangered Old World Monkey, the Yunnan snub-nosed monkey (Rhinopithecus bieti) from China. This library contains a total of 136 320 BAC clones. The average insert size of BAC clones was estimated to be 148 kb. The percentage of small inserts (50-100 kb) is 2.74%, and only 2.67% non-recombinant clones were observed. Assuming a similar genome size with closely related primate species, the Yunnan snub-nosed monkey BAC library has at least six times the genome coverage. By end sequencing of randomly selected BAC clones, we generated 201 sequence tags for the library. A total of 139 end-sequenced BAC clones were mapped onto the chromosomes of Yunnan snub-nosed monkey by fluorescence in-situ hybridization, demonstrating a high degree of synteny conservation between humans and Yunnan snub-nosed monkeys. Blast search against human genome showed a good correlation between the number of hit clones and the size of the chromosomes, an indication of unbiased chromosomal distribution of the BAC library. This library and the mapped BAC clones will serve as a valuable resource in comparative genomics studies and large-scale genome sequencing of nonhuman primates. The DNA sequence data reported in this paper were deposited in GenBank and assigned the accession number CG891489-CG891703.

Animals↗

PubMed2004

Construction and characterization of bacterial artificial chromosome library of black-handed spider monkey (Ateles geoffroyi).

The large-insert genomic DNA library is a critical resource for genome-wide genetic dissection of target species. We constructed a high-redundancy bacterial artificial chromosome (BAC) library of a New World monkey species, the black-handed spider monkey (Ateles geoffroyi). A total of 193 152 BAC clones were generated in this library. The average insert size of the BAC clones was estimated to be 184.6 kb with the small inserts (50-100 kb) accounting for less than 3% and the non-recombinant clones only 1.2%. Assuming a similar genome size with humans, the spider monkey BAC library has about 11x genome coverage. In addition, by end sequencing of randomly selected BAC clones, we generated 367 sequence tags for the library. When blasted against human genome, they showed a good correlation between the number of hit clones and the size of the chromosomes, an indication of unbiased chromosomal distribution of the library. This black-handed spider monkey BAC library would serve as a valuable resource in comparative genomic study and large-scale genome sequencing of nonhuman primates.

Animals↗

PubMed2003

Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3.

Interleukin 1 receptor (IL-1R) and Toll-like receptors (TLRs) induce inflammatory genes through the complex of MyD88, IL-1R-associated protein kinase (IRAK) and tumor necrosis factor receptor-associated factor 6 (TRAF6), which is believed to function 'upstream' of the cascades of IkappaB kinase (IKK) and nuclear factor-kappaB (NF-kappaB); extracellular signal-regulated protein kinase (ERK); c-Jun N-terminal kinase (JNK); and p38 mitogen-activated protein kinase (MAPK). Here we show that MAPK-ERK kinase kinase (MEKK3) is an essential signal transducer of the MyD88-IRAK-TRAF6 complex in IL-1R-TLR4 signaling. MEKK3 forms a complex with TRAF6 in response to IL-1 and lipopolysaccharide (LPS) but not CpG, and is required for IL-1R- and TLR4-induced IL-6 production. Furthermore, MEKK3 is crucial for IL-1- and LPS-induced activation of NF-kappaB and JNK-p38 but not ERK, indicating that MAPKs are differentially activated during IL-1R-TLR4 signaling. These data demonstrate that MEKK3 is crucial for IL-1R and TLR4 signaling through the IKK-NF-kappaB and JNK-p38 MAPK pathways.*Note: In the version of this article originally published online, the third author's name was incorrect. The correct author name should be Yong Lin. This error has been corrected for the HTML and print versions of this article.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Translation inhibitors sensitize prostate cancer cells to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by activating c-Jun N-terminal kinase.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in several human tumors both in vitro and in vivo, however, some tumors remain resistant for poorly understood reasons. Using a quantitative DNA fragmentation assay for apoptosis, we have shown that human prostate cancer cells are resistant to a wide range of TRAIL doses up to 500 ng/ml. However, translation inhibitors, such as anisomycin, cycloheximide, emetine, harringtonine, and puromycin, unlike several transcription inhibitors, significantly sensitized PC3-neomycin (PC3-neo) cells to TRAIL-induced apoptosis. These effects were inhibited in PC3 cells engineered to express bcl2 (PC3-bcl2). Translation inhibitors led to activation of c-Jun N-terminal kinase (JNK), which plays a role in this sensitization process because inhibition of JNK activation resulted in protection against TRAIL plus translation inhibitor-induced apoptosis. JNK activation may be required for this process, but it is not sufficient because activation of JNK using an MEKK2 expression vector did not mimic the sensitizing effect of translation inhibitors. Other stress-activated protein kinases, such as ERK and p38, play an insignificant role in determining the apoptotic sensitivity. We conclude that activation of JNK is required for sensitization of PC3 cells to TRAIL-induced apoptosis by translation inhibitors in cells that are otherwise TRAIL-resistant. However, in addition to JNK activation, other aspects of translation inhibition such as the suppressed activity of apoptosis-inhibitory proteins or activation of other signal transduction pathways must also be involved.

Activating Transcription Factor 2↗

PubMed2003

Stimulation of lipocalin-type prostaglandin D synthase by retinoic acid coincides with inhibition of cell proliferation in human 3AO ovarian cancer cells.

Lipocalin-type prostaglandin D synthase (LPGDS; PGH(2)D-isomerase; EC 5.3.99.2) is a bifunctional protein first identified in the mammalian brain. It acts as a PGD(2)-producing enzyme and a retinoid transporter. Recent studies have shown that LPGDS is anomalously expressed in ovarian tumors and that retinoid may have a role as an ovarian cancer chemotherapeutic agent. To determine whether there is a relationship between retinoid and LPGDS in ovarian tumors, we examined the regulation of the gene encoding LPGDS by all-trans retinoic acid (RA). Real-time quantitative RT-PCR analysis showed that RA strongly induced the accumulation of LPGDS mRNA in human 3AO ovarian cancer cells. Furthermore, treatment of the cells with RA induced the synthesis and secretion of LPGDS into the culture medium. This increased expression of LPGDS was accompanied by an inhibition of cell proliferation in the ovarian cancer cells. Prostaglandin D synthase, ovarian cancer, retinoic acid, real-time quantitative RT-PCR.

Carrier Proteins↗

PubMed2003

The death domain kinase RIP1 is essential for tumor necrosis factor alpha signaling to p38 mitogen-activated protein kinase.

The cytokine tumor necrosis factor alpha (TNF-alpha) stimulates the NF-kappaB, SAPK/JNK, and p38 mitogen-activated protein (MAP) kinase pathways by recruiting RIP1 and TRAF2 proteins to the tumor necrosis factor receptor 1 (TNFR1). Genetic studies have revealed that RIP1 links the TNFR1 to the IkappaB kinase (IKK) complex, whereas TRAF2 couples the TNFR1 to the SAPK/JNK cascade. In transfection studies, RIP1 and TRAF2 stimulate p38 MAP kinase activation, and dominant-negative forms of RIP1 and TRAF2 inhibit TNF-alpha-induced p38 MAP kinase activation. We found TNF-alpha-induced p38 MAP kinase activation and interleukin-6 (IL-6) production impaired in rip1(-/-) murine embryonic fibroblasts (MEF) but unaffected in traf2(-/-) MEF. Yet, both rip1(-/-) and traf2(-/-) MEF exhibit a normal p38 MAP kinase response to inducers of osmotic shock or IL-1alpha. Thus, RIP1 is a specific mediator of the p38 MAP kinase response to TNF-alpha. These studies suggest that TNF-alpha-induced activation of p38 MAP kinase and SAPK/JNK pathways bifurcate at the level of RIP1 and TRAF2. Moreover, endogenous RIP1 associates with the MAP kinase kinase kinase (MAP3K) MEKK3 in TNF-alpha-treated cells, and decreased TNF-alpha-induced p38 MAP kinase activation is observed in Mekk3(-/-) cells. Taken together, these studies suggest a mechanism whereby RIP1 may mediate the p38 MAP kinase response to TNF-alpha, by recruiting the MAP3K MEKK3.

Animals↗

PubMed2003

[Changes of alkaline phosphatase sugar chains in hepatocellular carcinoma tissue].

OBJECTIVE: To investigate the changes of sugar chain structures of alkaline phosphatase (ALP) in hepatoma tissue and its relation to the invasiveness of hepatocellular carcinoma (HCC). METHODS: The binding ratios of ALP from 9 normal liver tissues, 16 hepatoma tissues and 16 noncancerous tissues surrounding hepatoma were analysed by affinity chromatography on various lectin columns including leukoagglutinating phytohemagglutinin (L-PHA), lentil lectin (LCA), Datura stramonium agglutinin (DSA), erythroagglutinating phytohemagglutinin (E-PHA) and Sambucus nigra bark agglutinin (SNA). RESULTS: The binding ratios of ALP on L-PHA (22.94%+/-5.30%), DSA (55.97%+/-13.72%), LCA (38.16%+/-8.87%), E-PHA (11.56%+/-4.81%) and SNA (69.80%+/-13.71%) in HCC tissues were significantly increased (P<0.01) compared with that in normal liver tissues (L-PHA 5.89%+/-2.75%, DSA 36.20%+/-11.58%, LCA 17.90%+/-6.71%, E-PHA 5.38%+/-2.20%, SNA 57.32%+/-11.27%), respectively. t values between the two groups were 8.94, 3.64, 5.94, 3.62 and 2.32, respectively. L-PHA-binding ratio (25.84%+/-4.67%) of ALP in HCC with invasiveness was significantly higher than that (18.10%+/-3.64%) without invasiveness (t=3.71, P<0.01). CONCLUSION: The changes of ALP sugar chain structures occur in HCC tissue. b1-6 branching sugar chain structure of ALP is related to the invasiveness of HCC.

Alkaline Phosphatase↗

PubMed2002

FKBP12 is the only FK506 binding protein mediating T-cell inhibition by the immunosuppressant FK506.

BACKGROUND: FK506-binding proteins (FKBP) are immunophilins that interact with the immunosuppressive drugs FK506 and rapamycin. Several FKBP family members such as FKBP12, FKBP12.6, and FKBP51 are expressed in T cells. It has been speculated that these FKBPs are possibly redundant in the immunosuppressant-induced T-cell inactivation. To determine the pharmacological relevance of multiple FKBP members in the immunosuppressant-induced T-cell inactivation, we have investigated the physiological responses of FKBP12-deficient and FKBP12.6-deficient mutant T cells to the immunosuppressive agent FK506. METHODS: FKBP12-deficient and FKBP12.6-deficient T cells were isolated from genetically engineered FKBP12-deficient and FKBP12.6-deficient mice, respectively. T-cell growth inhibitory assay was used to assess their responses to immunosuppressant FK506 treatments. RESULTS: We found that growth inhibition induced by FK506 is abolished in FKBP12-deficient cells but not in FKBP12.6-deficient cells. CONCLUSIONS: FKBP12 is the only FKBP family member that plays a key role in immunosuppressant-mediated immunosuppression.

Animals↗

PubMed2002

Tissue factor expression and angiogenesis in human glioma.

BACKGROUND: Tissue factor (TF), a cell surface receptor of factor VII/VIIa, was initially recognized as an initiator of the extrinsic coagulation pathway. TF has recently been found to be expressed highly in certain types of malignant tumors. In addition, TF expression appears to be a marker for malignant angiogenesis in human solid tumors. However TF expression and its relationship to angiogenesis and tumor progression in human glioma are still unclear. METHODS: Quantitative reverse transcription PCR and immunofluorescence were performed on the U251 glioma cell line, 5 normal brain specimens, and 34 glioma surgical specimens. Of the gliomas, 10 were grade IV, 12 grade III, 7 grade II, and 5 grade I. Microvessels were highlighted using a monoclonal antibody specific to human von Willebrand factor. RESULTS: TF was strongly positive in 90% of the grade IV cases, 58% of grade III, 43% of grade II, and 20% of grade I. TF staining was not present in any normal brain specimens. The mean level of TF mRNA in normal brain tissue was 5.0 x 10(3) copies/microg RNA. Among the gliomas, TF mRNA ranged from 1.7 x 10(5) to 6.8 x 10(7) copies/microg, with a mean of 4.6 x 10(6). TF expression was highest in glioblastomas that showed greatest vascularity. CONCLUSIONS: These findings support a role for TF in angiogenesis in glioma. TF is expressed in glioma and the level of expression correlates with the histologic grade of malignancy and vascularity.

Antigens↗

PubMed2002

Production of extracellular domain of human tissue factor using maltose-binding protein fusion system.

Making use of the physiological process of coagulation as an anti-tumor effector function may be beneficial in various coagulation-mediated diseases. Preclinical and clinical studies with novel tissue factor targeting constructs require that efficient procedures for preparing large quantities of pure truncated TF (tTF) become available. In this study, we described a simple and rapid on-column method for purifying large quantities of human tTF from Escherichia coli. The coding region of extracellular domain of tissue factor was linked to the 3(')-end of maltose-binding protein (MBP) gene. The fusion protein was expressed as soluble form after induction by isopropylthio-beta-D-galactoside (IPTG). MBP-tTF was purified by amylose affinity chromatography. MBP can be removed by digestion with factor Xa. Expression could represent 21.5% of the total soluble protein in E. coli, allowing approximately 15mg of highly purified protein to be obtained per liter of bacterial culture. The fusion protein was recognized in Western blot by anti-TF monoclonal antibody and the activity was confirmed by chromogenic assay. This MBP-fusion system permits large-scale functional expression and purification of recombinant soluble proteins, providing a basis for the future study of structure and function of tTF.

Blotting, Western↗

PubMed2002

Disruption of Mekk2 in mice reveals an unexpected role for MEKK2 in modulating T-cell receptor signal transduction.

MEKK2 is a member of the mitogen-activated protein kinase (MAPK) kinase kinase gene family involved in regulating multiple MAPK signaling pathways. To elucidate the in vivo function of MEKK2, we generated mice carrying a targeted mutation in the Mekk2 locus. Mekk2(-/-) mice are viable and fertile. Major subsets of thymic and spleen T cells in Mekk2-deficient mice were indistinguishable from those in wild-type mice. B-cell development appeared to proceed similarly in the bone marrow of Mekk2-deficient and wild-type mice. However, Mekk2(-/-) T-cell proliferation was augmented in response to anti-CD3 monoclonal antibody (MAb) stimulation, and these T cells produced more interleukin 2 and gamma interferon than did the wild-type T cells, suggesting that MEKK2 may be involved in controlling the strength of T-cell receptor (TCR) signaling. Consistently, Mekk2(-/-) thymocytes were more susceptible than wild-type thymocytes to anti-CD3 MAb-induced cell death. Furthermore, TCR-mediated c-Jun N-terminal kinase activation was not blocked but moderately enhanced in Mekk2(-/-) T cells. Neither extracellular signal-regulated kinase nor p38 MAPK activation was affected in Mekk2(-/-) T cells. In conclusion, we found that MEKK2 may be required for controlling the strength of TCR/CD3 signaling.

Animals↗

PubMed2002

Quantitative reverse transcription-PCR measurement of tissue factor mRNA in glioma.

BACKGROUND: Initiation of the coagulation serine protease cascade in mammalian cells is mediated by tissue factor (TF), which is a cell surface receptor and cofactor for coagulation factor VII (FVII) and its activated form FVII (FVIIa). Increasing evidence suggests that TF is expressed in a wide range of cancer cells and plays important roles in cancer progression and metastasis. In this study, we investigated the association between the expression level of TF transcript and histologic features of glioma. METHODS: RNA was extracted from normal brain tissues and glioma tissues. We developed and validated a real-time quantitative reverse transcription (RT)-PCR assay, based on fluorescent TaqMan methodology, to quantify TF gene expression and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) at the mRNA level in human glioma. RESULTS: The dynamic range of the assay was 10(3)-10(8) copy/microg RNA. The relationship between Ct and log starting concentration was linear (r2 > or = 0.99). The mean expression of TF in healthy brain tissue was 6.2 x 10(3) copy/microg RNA. Overexpression of TF was found in 42 brain glioma samples, mean value is 2.9 x 10(6) copy/microg RNA. CONCLUSIONS: TF mRNA transcript is expressed in glioma and the level of expression correlates with histologic grade of malignancy. This new simple, rapid, semiautomated assay is a major alternative to Northern blot and competitive quantitative PCR for gene alteration analysis in human tumors and may be a powerful tool for large randomized, prospective cooperative group trials and support future TF-based clinical applications.

Biomarkers, Tumor↗

PubMed2001

The dual origin and Siberian affinities of Native American Y chromosomes.

The Y chromosomes of 549 individuals from Siberia and the Americas were analyzed for 12 biallelic markers, which defined 15 haplogroups. The addition of four microsatellite markers increased the number of haplotypes to 111. The major Native American founding lineage, haplogroup M3, accounted for 66% of male Y chromosomes and was defined by the biallelic markers M89, M9, M45, and M3. The founder haplotype also harbored the microsatellite alleles DYS19 (10 repeats), DYS388 (11 repeats), DYS390 (11 repeats), and DYS391 (10 repeats). In Siberia, the M3 haplogroup was confined to the Chukotka peninsula, adjacent to Alaska. The second major group of Native American Y chromosomes, haplogroup M45, accounted for about one-quarter of male lineages. M45 was subdivided by the biallelic marker M173 and by the four microsatellite loci alleles into two major subdivisions: M45a, which is found throughout the Americas, and M45b, which incorporates the M173 variant and is concentrated in North and Central America. In Siberia, M45a haplotypes, including the direct ancestor of haplogroup M3, are concentrated in Middle Siberia, whereas M45b haplotypes are found in the Lower Amur River and Sea of Okhotsk regions of eastern Siberia. Among the remaining 5% of Native American Y chromosomes is haplogroup RPS4Y-T, found in North America. In Siberia, this haplogroup, along with haplogroup M45b, is concentrated in the Lower Amur River/Sea of Okhotsk region. These data suggest that Native American male lineages were derived from two major Siberian migrations. The first migration originated in southern Middle Siberia with the founding haplotype M45a (10-11-11-10). In Beringia, this gave rise to the predominant Native American lineage, M3 (10-11-11-10), which crossed into the New World. A later migration came from the Lower Amur/Sea of Okhkotsk region, bringing haplogroup RPS4Y-T and subhaplogroup M45b, with its associated M173 variant. This migration event contributed to the modern genetic pool of the Na-Dene and Amerinds of North and Central America.

Alleles↗