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Biomedical subjects

D Yu

Publications and source records attributed to D Yu.

At least 73 records · Page 4Linked to original sources

[Clinical study of P-gp, and bcl-2 protein expression in non-Hodgkin's lymphomas patients].

OBJECTIVE: To investigate the relationship between the expression of P-gp, P26-bcl-2 and the prognosis in intermediate and high grade non-Hodgkin's lymphomas (NHL). METHODS: Sixty cases of intermediate and high grade NHL were retrospectively reviewed using immunohistochemical method. All patients were received CHOP chemotherapy over 4 courses. RESULTS: P-gp was identified in 15 and P26-bcl-2 in 25 cases. The 3-year survival rates for patients with P26-bcl-2 (+) and P26-bcl-2 (-) were 37.64% and 76.80%, respectively (P < 0.005), and for patients with both positive P-gp and P26-bcl-2 and both negative were 15.38% and 48.48%, respectively (P = 0.038). CONCLUSIONS: There is direct relationship between the P-gp, P26-bcl-2 protein expression and the prognosis in intermediate and high grade non-Hodgkin's lymphoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Expression of VEGF-C and its correlation with cervical lymph nodes metastasis of oral cancers].

OBJECTIVE: Vascular endothelial growth factor C (VEGF-C) is known to be capable of inducing cell proliferation of lymphatic endothelia and development of lymphatic vessels. Thus, in the current study the expression of VEGF-C was investigated to understand the mechanism of lymphatic metastasis of oral cancer. METHODS: VEGF-C protein expression in benign and malignant oral lesions was investigated with an immunohistochemical staining assay, followed by light microscopic examination and image analysis. RESULTS: Immunohistostaining of VEGF-C was observed in normal, benign and malignant epithelia, as well as in some lymphatic vessels. The VEGF-C positive rate was significantly higher in squamous carcinomas than in normal tissues and benign lesions. It was also noted that in squamous carcinomas the expression level of VEGF-C correlated well with pathological grades and stages of lymph node metastasis, but not with clinical grades. CONCLUSION: These findings suggest that VEGF-C may promote lymphatic metastasis of oral cancer, and it is possible to be used as a predictor for the lymphatic metastasis and prognosis of oral cancer.

Carcinoma, Squamous Cell↗

[Linkage of allergic rhinitis with HLA-DRB alleles polymorphism].

OBJECTIVE: To investigate whether susceptibility or resistance to allergic rhinitis associated with HLA-DRB alleles. METHOD: Using PCR-SSP (sequence-specific primer polymerase chain reaction), we tested the frequency distribution of HLA-DRB alleles in 41 patients with allergic rhinitis (AR) and 41 healthy controls from Beijing China. RESULT: The frequence of HLA-DRB1 * 0301.2 and HLA-DRB4 * 0101 was lower in AR than in controls (2.44% vs 17.07%, P < 0.05; 29.27% vs 51.22%, P < 0.05). CONCLUSION: HLA-DRB1 * 0301.2 and HLA-DRB4 * 0101 alleles might confer protection against AR.

Adult↗

[Auricular cartilage palisade technique for repairing tympanic membrane perforation].

OBJECTIVE: To study the auricular cartilage palisade technique for repairing tympanic membrane perforation. METHOD: Sixty-six cases of large tympanic membrane perforation were treated with auricular cartilage. The results were compared with that of temporal fascia repairing in 60 ears. RESULTS: The closure rates of tympanic membrane perforation were 92.4% in cartilage group and 80% in temporal fascia group, respectively. There was no significant difference between two groups in hearing improvement. The cartilage is quite suitable for repairing large perforation of the tympanic membrane and for treating adhesive otitis media. CONCLUSION: The auricular cartilage palisade technique is an ideal method for repairing tympanic membrane perforation.

Adult↗

[Endoscopic surgery for nasal inverted papilloma].

OBJECTIVE: To study and perfect the endoscopic surgery for nasal inverted papilloma(IP) and to decrease the recurrence after operation. METHODS: Forty-seven cases who were diagnosed as nasal IP were divided into two groups according to the tumor extension and operated upon and observed for 12-40 months (average 24.6 months). 51% of all cases had been operated on for 1-3 times before the treatment. Thirty-six cases in which the tumor had invaded the lateral nasal wall, middle meatus, partial or total ethmoid and/or sphenoid and infiltrated around the natural ostium of the maxillary sinus had performed transnasal endoscopic surgical procedures(TNESP). Another group (9 cases) in which involvement of the IP had further extended, into the maxillary sinus, had been treated by combination transnasal and Caldwell-Luc endoscopic surgical procedures (CTESP). In order to decrease bleeding during the operation, the body and bases of the IP were irradiated with YAG laser. The tumor was removed using the shaver system. The bony attachment of the IP and neighboring tissues were irradiated in all cases. RESULTS: Forty-five (95.7%) cases were not recurrent. The recurrence of the IP was identified in two cases (4.3%). But in 6 cases (12.8%), during postoperative follow-up management (1-3 months postoperatively) small mass of the IP (pathologically identified) were observed and removed and irradiated with YAG laser immediately. The recurrence was not observed in the one year follow-up period. CONCLUSION: Endoscopic surgical technique combining the irradiation of YAG laser and the application of shaver system is recommended. This procedure was effective and led to a decreased recurrence rate.

Adolescent↗

[Relationship between three inner ear antigens and autoimmune inner ear disease].

OBJECTIVE: To investigate the relationship between three purified inner ear antigens and autoimmune inner ear disease (AIED), and to determine their expressions in normal guinea pig cochleas. METHODS: Guinea pigs were divided into group B, group C and group D and immunized respectively with three subcomponents of crude inner ear antigens (31,000, 42,000-45,000 and 60,000 proteins). Hearing thresholds, serum IgG levels and morphological changes of inner ear were observed. The protein expressions of these antigens were examined by immunohistochemistry. In the control group, antigens were replaced by gel homogenate of polyacrylamide. RESULTS: There were no significant differences of hearing threshold among groups before immunization with inner ear antigens (F = 0.07, P > 0.05). There were no significant changes of hearing thresholds and inner ear morphology in group C and control group. Hearing thresholds dropped in part of animals immunized with 31,000 or 60,000 protein. Hearing threshold of group B and D changed significantly after immunization, as compared with the control group(F = 9.12, P < 0.01). Serum IgG levels increased significantly in all experimental groups compared with the control group(F = 7.46, P < 0.01). The 31,000 protein distributed strictly in cochlear nerve, and 42,000-45,000 or 60,000 protein distributed widely, including the spiral ganglion, Corti's organ, stria vascularis and spiral ligament. CONCLUSIONS: Two subcomponents of 31,000 and 60,000 in crude inner ear antigen could induce autoimmune inner ear disease. The distribution of 31,000 protein was more tissue specific and might be used as a marker protein for clinical diagnosis of autoimmune inner ear disease.

Animals↗

Overexpression of ErbB2 in cancer and ErbB2-targeting strategies.

This past decade has witnessed the remarkable advances in the understanding of the role of the erbB2 gene in cancers and the stunning progress in developing targeted therapies for erbB2-overexpressing cancers. Activation of the ErbB2 receptor signaling pathways can enhance various metastasis-associated properties that lead to an increase of cancer metastasis. Additionally, ErbB2 overexpression confers therapeutic resistance via receptor-mediated antiapoptotic signals. To limit these disastrous effects of the overexpressed ErbB2, various ErbB2-blocking strategies have been developed in the laboratories and several have been tested in clinical trials or approved as therapies for ErbB2 overexpressing cancers. In this article, we will discuss the detrimental effects of the erbB2 gene in cancers, with a focus on breast cancer. We will also outline ErbB2-targeting strategies as potential therapies for ErbB2-overexpressing cancers. Progress in understanding the molecular biology of ErbB2 and in molecular-based treatment of ErbB2-overexpressing tumors will bring great benefits to cancer patients.

Animals↗

Accessible 5'-end of CpG-containing phosphorothioate oligodeoxynucleotides is essential for immunostimulatory activity.

In our ongoing efforts to decipher the sequence and structural requirements in the flanking region of the CpG motif in phosphorothioate oligodeoxynucleotides (PS-oligos), we have examined the requirement of free 5'- and 3'-ends of PS-oligos on immune stimulation. Our model studies using 3'-3'-linked (containing two free 5'-ends) and 5'-5'-linked (containing two free 3'-ends) CpG-containing PS-oligos demonstrate that immunostimulatory activity is significantly reduced when the 5'-end of the PS-oligo is not accessible, rather than the 3'-end, suggesting that the 5'-end plays a critical role in immunostimulatory activity.

Adjuvants, Immunologic↗

Assay of glutathione in individual mouse peritoneal macrophages by capillary zone electrophoresis with electrochemical detection.

Glutathione (GSH) in individual mouse peritoneal macrophages was determined by capillary zone electrophoresis with electrochemical end-column amperometric detection at a gold/mercury amalgam microelectrode. A capillary of 20 microm inner diameter was suitable for determination of GSH in an individual macrophage with a good signal-to-noise ratio. Individual macrophages could be drawn into the capillary with the aid of a inverted microscope. Lysing cells was studied in different buffer solutions. 0.01 mol/liter NaOH was selected to lyse macrophages. In this method, the usual calibration curve of GSH could not be used for the quantification of GSH in individual macrophages. It was found that standard GSH injected after analyzing each cell could be served as external standard. The whole cell injection and the lack of necessity of a derivatization reaction lead to more accurate and precise results. The average amount of GSH in an individual mouse peritoneal macrophage is 5.8 fmol, which is consistent with the literature value.

Animals↗

C-erbB-2/ HER-2 upregulates fascin, an actin-bundling protein associated with cell motility, in human breast cancer cell lines.

The over-expression of c-erbB-2/ HER-2, a receptor tyrosine kinase, correlates with poor prognosis in patients with breast and ovarian cancer. In the human breast cancer cell line, MDA-MB-435, c-erbB-2 over-expression results in increased chemoinvasion and higher metastatic properties in nude mice. However, the mechanisms by which c-erbB-2 increases the malignant potential of cells remains unclear. We have determined that over-expression of c-erbB-2 in MDA-MB-435 cells, and in some additional breast cancer cell lines, is associated with graphic increases in mRNA and protein levels of the actin bundling protein fascin. Heightened fascin expression has been observed in other systems to result in greatly increased cell motility, and indeed, our work employing semi-automated time-lapse microscopy demonstrates that MDA-MB-435 cells over-expressing c-erbB-2 exhibit significantly heightened cellular dynamics and locomotion, while visualization of bundled microfilaments within fixed cells revealed enhanced formation of dendritic-like processes, microspikes and other dynamic actin based structures. To address the means by which c-erbB-2 over-expression might result in elevated fascin levels, we identified multiple perfect match TCF and NF-kappaB consensus sites in fascin's promoter and first intron, which appeared consistent with the greater endogenous transcriptional activities of TCF and NF-kappaB in c-erbB-2 over-expressing MDA-MB-435 cells. While such transcriptional modulation may occur in the context of the intact gene/chromatin, subsequent tests using reporter constructs did not support involvement of these signaling pathways. In conclusion, highly increased fascin levels were observed in MDA-MB-435 over-expressing c-erbB-2, likely contributing to these cells' altered actin dynamics, and increased cell motility and malignancy. Studies in progress aim to discern the means by which c-erbB-2 over-expression leads to transcriptional activation of the fascin gene.

Actins↗

Wild-type p53 suppresses angiogenesis in human leiomyosarcoma and synovial sarcoma by transcriptional suppression of vascular endothelial growth factor expression.

Our recent studies (R. Pollock et al., Clin. Cancer Res., 4: 1985-1994, 1998; M. Milas et al., Cancer Gene Ther., in press, 2000) have shown that the restoration of wild-type (wt) p53 enhances cell cycle control in vitro and inhibits the growth of human soft-tissue sarcoma in severe combined immunodeficient mice. We hypothesized that the antitumor effect of wt p53 overexpression in sarcoma cells is attributable not only to enhanced cell cycle control but also to inhibition of angiogenesis. We evaluated the effect of restoring wt p53 function on angiogenesis in human soft-tissue sarcoma harboring mutant p53. Restoration of wt p53 expression in human leiomyosarcoma SKLMS-1 cells that contain mutant p53 markedly inhibited angiogenesis induced by tumor cells in vivo. Angiogenesis assays using an in vivo Matrigel plug assay demonstrated that less neovascularization in severe combined immunodeficient mice was observed with conditioned medium (CM) from human synovial sarcoma cells expressing wt p53 compared with CM from human synovial sarcoma cells expressing mutant p53. Microvessel density and microvessel counts were lower in tumor xenografts from cells containing wt p53 than in tumor xenografts from cells containing mutant p53. The growth and migration of murine lung endothelial cells were decreased when cells were treated with CM from sarcoma cells expressing wt p53 compared with CM from sarcoma cells expressing mutant p53. The introduction of wt p53 into sarcoma cells containing mutant p53 significantly reduced the expression of vascular endothelial growth factor (VEGF), which is a key mediator of tumor angiogenesis. Stimulation of endothelial cell migration by CM from cells expressing mutant p53 was significantly reduced after anti-VEGF neutralizing antibody was added to the CM. Using luciferase as the reporter of VEGF promoter activity, we found that wt p53 inhibited VEGF promoter activity in SKLMS-1 cells. Deletion analysis defined an 87-bp region (bp -135 to -48) in the VEGF promoter that is necessary for inhibiting VEGF promoter activity by wt p53. The transcription factor Sp1 may be involved in the repression of VEGF promoter activity by wt p53 in SKLMS-1 cells. These data indicated that wt p53 can suppress angiogenesis in human soft-tissue sarcomas by transcriptional repression of VEGF expression.

Animals↗

An efficient recombination system for chromosome engineering in Escherichia coli.

A recombination system has been developed for efficient chromosome engineering in Escherichia coli by using electroporated linear DNA. A defective lambda prophage supplies functions that protect and recombine an electroporated linear DNA substrate in the bacterial cell. The use of recombination eliminates the requirement for standard cloning as all novel joints are engineered by chemical synthesis in vitro and the linear DNA is efficiently recombined into place in vivo. The technology and manipulations required are simple and straightforward. A temperature-dependent repressor tightly controls prophage expression, and, thus, recombination functions can be transiently supplied by shifting cultures to 42 degrees C for 15 min. The efficient prophage recombination system does not require host RecA function and depends primarily on Exo, Beta, and Gam functions expressed from the defective lambda prophage. The defective prophage can be moved to other strains and can be easily removed from any strain. Gene disruptions and modifications of both the bacterial chromosome and bacterial plasmids are possible. This system will be especially useful for the engineering of large bacterial plasmids such as those from bacterial artificial chromosome libraries.

Bacteriophage lambda↗

Immunostimulatory activity of CpG containing phosphorothioate oligodeoxynucleotide is modulated by modification of a single deoxynucleoside.

Phosphorothioate oligodeoxynucleotides (PS-oligos) containing the CpG motif have immunostimulatory properties. Our earlier study had shown that the immunostimulatory activity of PS-oligos containing the CpG motif can be modulated by incorporation of 2'-O-methylribonucleosides (Zhao, Q.; Yu, D.; Agrawal, S. Bioorg. Med. Chem. Lett. 1999, 9, 3453). Here we show that the immunostimulatory activity of a PS-oligo containing a CpG motif can be modulated by substitution of a single deoxynucleoside at specific sites with either 2'-O-methylribonucleoside or 3'-O-methylribonucleoside in the flanking region to CpG motif. Furthermore, substitution of deoxynucleosides with 2'-O-methoxyethoxyribonucleosides also results in modulating immunostimulatory activity of PS-oligos.

Animals↗

Measurement of chloramphenicol by capillary zone electrophoresis following end-column amperometric detection at a carbon fiber micro-disk array electrode.

Capillary zone electrophoresis was employed for the measurement of chloramphenicol using end-column amperometric detection with a carbon fiber micro-disk array electrode, at a constant potential of -1.00 V vs. saturated calomel electrode. The effect of oxygen in the buffer has been investigated. It is found that when the area of the carbon fiber electrode is smaller than 1.1 mm2, the interference of oxygen can be overcome. In this procedure deoxygenation is not necessary. The effect of pH, the concentration of the buffer and the high separation voltage across the capillary on the migration time, electrophoretic peak current and separation efficiency has been studied. The optimum conditions of separation and detection are 8.4x10(-4) mol/l HOAc-3.2x10(-3) mol/l NaOAc for the buffer solution, 20 kV for the separation voltage, 5 kV and 5 s for the injection voltage and the injection time, respectively. The calibration plot was found to be linear in the range 5x10(-6) to 1x10(-3) mol/l and the limit of detection is 9.1x10(-7) mol/l or 1.4 fmol (S/N=2). The relative standard deviation is 1.1% for the migration time and 2.3% for the electrophoretic peak current. The method was applied to the determination of chloramphenicol in human serum.

Anti-Bacterial Agents↗

A new method of quantification of pipemidic-acid by capillary zone electrophoresis with end-column amperometric detection.

Capillary zone electrophoresis was employed for the determination of pipemidic acid using an end-column amperometric detection with a carbon fiber microdisk array electrode, at a constant potential of -1.10 V vs. saturated calomel electrode. The optimum conditions of separation and detection were 1.2 x 10(-4) mol/LNaOAc - 8.8 x 10(-4) mol/ LHOAc for the buffer solution, 20 kV for the separation voltage, 5 kV and 10 s for the injection voltage and the injection time. The limit of detection was 1.05 x 10(-7) mol/L or 189 amol (S/N=3). The relative standard deviation was 0.31% for the migration time and 2.0% for the electrophoretic peak current. The method was applied to determining pipemidic acid in human serum.

Anti-Infective Agents↗

Monitoring myoglobin by capillary zone electrophoresis with end-column amperometric detection.

Capillary zone electrophoresis was employed for the determination of myoglobin in human urine using end-column amperometric detection with a carbon fiber microelectrode at a constant potential of 1.80 V vs. saturated calomel electrode (SCF). The optimum conditions of separation and detection are: 3.73 x 10-4 mol/L sodium diethyl malonyl urea (barbitone sodium), 1.34 x 10-4 mol/L HCl for the buffer solution, 20 kV for separation voltage, 5 kV and 5 s for injection voltage and injection time, respectively. The limit of detection is 4.4 x 10-8 mol/L or 84 amole signal to noise (S/N = 2). The relative standard deviation is 2.9% for the migration time and 2.5% for the electrophoretic peak current. The method can be used for the determination of myoglobin in human urine. The samples can be directly injected and need no pretreatment. The method is also rapid, less than 2 min, and has a recovery rate of 94-106%.

Electrophoresis, Capillary↗

Capillary electrophoresis/electrochemical detection system with on-line deoxygenation.

A capillary electrophoresis (CE)/electrochemical detection system with on-line deoxygenation was developed, consisting of a deoxygenation injector, a deoxygenation protector, and an electrochemical detection cell. When the system was utilized for 60 min, the steady-state current of oxygen detected could be dropped to 3% of the original value for the gold/mercury amalgam electrode and to 8% of the original value for the gold electrode, and the limit of detection could be decreased two orders of magnitude for the reducible analytes such as TI+ (from 3.1 x 10-5 mol/L to 8.0 x 10-7 mol/L) and metronidazole (from 3.8 x 10-5 mol/L to 4.0 x 10-7 mol/L).

Electrochemistry↗

Role of erbB2 in breast cancer chemosensitivity.

The erbB2 gene, which encodes a transmembrane growth factor receptor, is overexpressed in approximately 30% of breast cancers. Overexpressing this gene makes breast cancers resistant to certain chemotherapeutic agents. In this article, we review what is known about ErbB2-mediated chemoresistance and the controversies surrounding it. We also examine the antiapoptotic function of erbB2 as one of the molecular mechanisms of ErbB2-mediated Taxol resistance and describe several emerging strategies for overcoming intrinsic ErbB2-mediated chemoresistance. Finally, we discuss future avenues for studies of chemosensitivity in ErbB2-overexpressing breast cancers that may lead to the development of effective biology-based treatment strategies.

Antibodies, Monoclonal↗