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101.
Gao W Kumar S Lotze MT Hanning C Robbins PD Gambotto A 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(1):107-113
Recently, several novel members of the IL-1 family have been identified. The possible therapeutic utility and the underlying biologic role of these new members remain unclear. In the present study we analyzed the anti-tumor activity of human IL-1 homologue 4(IL-1H4; renamed IL-F7) by adenovirus-mediated gene transfer (AdIL-1H4) directly into murine tumors. In vitro expression analysis showed that IL-1H4 was a secretory protein. Treatment of an established MCA205 mouse fibrosarcoma by single intratumoral injection of AdIL-1H4 resulted in significant growth suppression. Furthermore, complete inhibition of tumor growth was observed following multiple injections of AdIL-1H4. The anti-tumor activity of IL-1H4 was abrogated in nude and SCID mice and in IL-12-, IFN-gamma-, or Fas ligand-deficient mice. In contrast, IL-1H4 was able to confer substantial anti-tumor effects in NKT-deficient mice. These results suggest that IL-1H4 could play an important role in the link between innate and adaptive immunity and may be useful for tumor immunotherapy. 相似文献
102.
Characterization of the chromosomal binding sites and dimerization partners of the viral oncoprotein Meq in Marek's disease virus-transformed T cells 总被引:4,自引:0,他引:4
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Levy AM Izumiya Y Brunovskis P Xia L Parcells MS Reddy SM Lee L Chen HW Kung HJ 《Journal of virology》2003,77(23):12841-12851
103.
The ATP binding cassette multidrug transporter LmrA and lipid transporter MsbA have overlapping substrate specificities 总被引:10,自引:0,他引:10
Reuter G Janvilisri T Venter H Shahi S Balakrishnan L van Veen HW 《The Journal of biological chemistry》2003,278(37):35193-35198
LmrA is an ATP binding cassette (ABC) multidrug transporter in Lactococcus lactis that is a structural and functional homologue of the human multidrug resistance P-glycoprotein MDR1 (ABCB1). LmrA is also homologous to MsbA, an essential ABC transporter in Escherichia coli involved in the trafficking of lipids, including Lipid A. We have compared the substrate specificities of LmrA and MsbA in detail. Surprisingly, LmrA was able to functionally substitute for a temperature-sensitive mutant MsbA in E. coli WD2 at non-permissive temperatures, suggesting that LmrA could transport Lipid A. LmrA also exhibited a Lipid A-stimulated, vanadate-sensitive ATPase activity. Reciprocally, the expression of MsbA conferred multidrug resistance on E. coli. Similar to LmrA, MsbA interacted with photoactivatable substrate [3H]azidopine, displayed a daunomycin, vinblastine, and Hoechst 33342-stimulated vanadate-sensitive ATPase activity, and mediated the transport of ethidium from cells and Hoechst 33342 in proteoliposomes containing purified and functionally reconstituted protein. Taken together, these data demonstrate that MsbA and LmrA have overlapping substrate specificities. Our observations imply the presence of structural elements in the recently published crystal structures of MsbA in E. coli and Vibrio cholera (Chang, G., and Roth, C. B. (2001) Science 293, 1793-1800; Chang, G. (2003) J. Mol. Biol. 330, 419-430) that support drug-protein interactions and suggest a possible role for LmrA in lipid trafficking in L. lactis. 相似文献
104.
OBJECTIVE: To reevaluate breast aspirates showing extracellular hyaline material (EHM) and globules to assess if clinicoradiologic and cytologic features could help in differentiating between benign and malignant lesions, especially collagenous spherulosis (CS) and adenoid cystic carcinoma (ACC). STUDY DESIGN: Fine needle aspiration was performed on 884 patients with breast lumps. The cytomorphologic features of 6 cases showing EHM, including classic hyaline globules (HGs), were analyzed in detail. Three cases also had hemorrhagic nipple discharge. Tissue diagnosis (4) and mammography (6) were available. RESULTS: Aspirate smears revealed high cellularity composed of monolayers: clusters of uniform, small cells; EHM; and HGs surrounded by similar cells. Benign naked nuclei and stromal fragments (4), nuclear pleomorphism (3), apocrine cells (2), foam cells (2), naked HGs (2) and spindle cells in proximity to HGs were also seen (4). Nipple discharge smears showed foam cells, erythrocytes (3) and epithelial cell clusters with hyaline material (1). The cytologic diagnosis was CS (4) and ACC (2). Histopathology confirmed the diagnosis of CS (2) and ACC (1). CONCLUSION: There may be a morphologic overlap between the cytomorphologic features of CS and ACC, leading to diagnostic errors. The presence of EHM and HGs in association with bland cellular features should be interpreted with caution to avoid erroneous diagnoses. Histopathology is mandatory in these cases because of their different prognostic implications. 相似文献
105.
Palmer LJ Buxbaum SG Larkin E Patel SR Elston RC Tishler PV Redline S 《American journal of human genetics》2003,72(2):340-350
Obstructive sleep apnea (OSA) is a common, chronic, complex disease associated with serious cardiovascular and neuropsychological sequelae and with substantial social and economic costs. Along with male gender, obesity is the most characteristic feature of OSA in adults. To identify susceptibility loci for OSA, we undertook a 9-cM genome scan in 66 white pedigrees (n=349 subjects) ascertained on the basis of either an affected individual with laboratory-confirmed OSA or a proband who was a neighborhood control individual. Multipoint variance-component linkage analysis was performed for the OSA-associated quantitative phenotypes apnea-hypopnea index (AHI) and body mass index (BMI). Candidate regions on chromosomes 1p (LOD score 1.39), 2p (LOD score 1.64), 12p (LOD score 1.43), and 19p (LOD score 1.40) gave the most evidence for linkage to AHI. BMI was also linked to multiple regions, most significantly to markers on chromosomes 2p (LOD score 3.08), 7p (LOD score 2.53), and 12p (LOD score 3.41). Extended modeling indicated that the evidence for linkage to AHI was effectively removed after adjustment for BMI, with the exception of the candidate regions on chromosomes 2p (adjusted LOD score 1.33) and 19p (adjusted LOD score 1.45). After adjustment for AHI, the primary linkages to BMI remained suggestive but were roughly halved. Our results suggest that there are both shared and unshared genetic factors underlying susceptibility to OSA and obesity and that the interrelationship of OSA and obesity in white individuals may be partially explained by a common causal pathway involving one or more genes regulating both AHI and BMI levels. 相似文献
106.
Molecular pathway for (-)-epigallocatechin-3-gallate-induced cell cycle arrest and apoptosis of human prostate carcinoma cells 总被引:15,自引:0,他引:15
Epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent present in green tea, is a promising chemopreventive agent. We recently showed that green tea polyphenols exert remarkable preventive effects against prostate cancer in a mouse model and many of these effects are mediated by the ability of polyphenols to induce apoptosis in cancer cells [Proc. Natl. Acad. Sci. USA 98 (2001) 10350]. Earlier, we showed that EGCG causes a G0/G1 phase cell cycle arrest and apoptosis of both androgen-sensitive LNCaP and androgen-insensitive DU145 human prostate carcinoma cells, irrespective of p53 status [Toxicol. Appl. Pharmacol. 164 (2000) 82]. Here, we provide molecular understanding of this effect. We tested a hypothesis that EGCG-mediated cell cycle dysregulation and apoptosis is mediated via modulation of cyclin kinase inhibitor (cki)-cyclin-cyclin-dependent kinase (cdk) machinery. As shown by immunoblot analysis, EGCG treatment of LNCaP and DU145 cells resulted in significant dose- and time-dependent (i) upregulation of the protein expression of WAF1/p21, KIP1/p27, INK4a/p16, and INK4c/p18, (ii) down-modulation of the protein expression of cyclin D1, cyclin E, cdk2, cdk4, and cdk6, but not of cyclin D2, (iii) increase in the binding of cyclin D1 toward WAF1/p21 and KIP1/p27, and (iv) decrease in the binding of cyclin E toward cdk2. Taken together, our results suggest that EGCG causes an induction of G1 phase ckis, which inhibits the cyclin-cdk complexes operative in the G0/G1 phase of the cell cycle, thereby causing an arrest, which may be an irreversible process ultimately leading to apoptotic cell death. This is the first systematic study showing the involvement of each component of cdk inhibitor-cyclin-cdk machinery during cell cycle arrest and apoptosis of human prostate carcinoma cells by EGCG. 相似文献
107.
Théberge JF Mehdi MZ Pandey SK Srivastava AK 《Archives of biochemistry and biophysics》2003,420(1):9-17
Vanadium salts such as vanadyl sulfate (VS), potent inhibitors of protein tyrosine phosphatases, have been shown to mimic, augment, and prolong insulin's action. However, the molecular mechanism of responses to these salts is not clear. In the present studies, we examined if VS-induced effects on insulin action are associated with enhancement or augmentation in the activation state of key components of the insulin signaling pathway. Treatment of insulin receptor-overexpressing cells with insulin or VS resulted in a time-dependent transient increase in phosphorylation and activation of extracellular signal-regulated kinases 1 and 2 (ERK 1/2) that peaked at about 5 min, then declined rapidly to about baseline within 30 min. However, when the cells were treated with VS before stimulation with insulin, sustained ERK 1/2 phosphorylation and activation were observed well beyond 60 min. VS treatment also prolonged the insulin-stimulated activation of phosphatidylinositol 3-kinase (PI3-K), which was associated with sustained interaction between insulin receptor substrate-1 (IRS-1) and the p(85 alpha) subunit of phosphatidylinositol 3-kinase (PI3-K) in response to insulin. These data indicate that prolongation of insulin-stimulated ERK 1/2 and PI3-K activation by VS is due to a more stable complex formation of IRS-1 with the p(85 alpha) subunit which may, in turn, be responsible for its ability to enhance and extend the biological effects of insulin. 相似文献
108.
Following the first two Frederick meetings on virus entry in 1997 [Cell 91 (1997) 721](1) and in 2000 [Cell 101 (2000) 697](2), further developments in our understanding of the multifactorial and multistage process of virus entry, and possible biomedical implications were presented and discussed in a lively fashion by leading scientists from around the world at the third Frederick meeting on the Cell Biology of Viral Entry (May 7-10, Frederick, MD) organized by R. Blumenthal (NCI-Frederick, NIH, Frederick) and E. Hunter (University of Alabama, Birmingham). Unlike the previous two meetings, non-enveloped viruses were not discussed this time, and the focus was how envelope glycoproteins (Envs) mediate entry into cells. Major topics included Env structure, virus receptors, entry intermediates, membrane fusion, fusion kinetics, and rafts. Virus envelope structures will be described in more detail here because the other topics are extensively discussed in the other chapters of this volume. 相似文献
109.
110.