12 results on '"Yip-Schneider, M T"'
Search Results
2. NOVEL MODEL OF ALCOHOL-INDUCED HEPATOCELLULAR CARCINOMA (HCC): 103
- Author
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Schmidt, C. M., Klein, P. J., Wentz, S. C., Hennig, M. E., Yip-Schneider, M. T., Matos-Bramblia, J. M., and Froehlich, J. C.
- Published
- 2007
3. Regulation of the Raf-1 kinase domain by phosphorylation and 14-3-3 association
- Author
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Yip-Schneider, M T, Miao, W, Lin, A, Barnard, D S, Tzivion, G, and Marshall, M S
- Subjects
Tyrosine 3-Monooxygenase ,hemic and immune systems ,Binding, Competitive ,Peptide Fragments ,Oncogene Protein pp60(v-src) ,Protein Structure, Tertiary ,Enzyme Activation ,Proto-Oncogene Proteins c-raf ,Phosphoserine ,14-3-3 Proteins ,Catalytic Domain ,COS Cells ,Mutation ,Animals ,Tetradecanoylphorbol Acetate ,Phosphorylation ,Research Article ,Protein Binding - Abstract
The Raf-1 kinase domain is kept in an inactive state by the N-terminal regulatory domain. Activation of the kinase domain occurs following release from the N-terminal repression and possible catalytic upregulation. To distinguish the regulatory mechanisms that directly influence the catalytic activity of the enzyme from those which act through the inhibitory domain, the catalytic domain of Raf-1 (CR3) was expressed in COS-7 cells. The role of phosphorylation in the direct regulation of this domain was determined by substituting non-phosphorylatable amino acids for known serine and tyrosine phosphorylation sites. The intrinsic activity of each mutant protein was determined as well as stimulation by v-Src and phorbol esters. Both v-Src and phorbol esters were potent activators of CR3, requiring the serine 338/339 (p21-activated protein kinase, Pak) and tyrosine 340/341 (Src) phosphorylation sites for full stimulation of CR3. In contrast, loss of the serine 497/499 protein kinase C phosphorylation sites had little effect on CR3 activation by either v-Src or phorbol esters. Loss of serine 621, a 14-3-3 adaptor-protein-binding site, prevented activation of CR3 by v-Src or phorbol esters and partially decreased the high basal activity of the kinase fragment. When co-expressed in COS-7 cells, 14-3-3 associated strongly with full-length Raf-1, weakly with wild-type CR3 and not at all with the A621 and D621 CR3 mutants. The role of 14-3-3 in maintaining the activity of the catalytic domain of Raf-1 was investigated further by performing peptide-competition studies with wild-type CR3, wild-type CR3 and v-Src or constitutively active CR3 (CR3[YY340/341DD]). In each case, incubation of the proteins with a phosphoserine-621 Raf-1 peptide, which we show displaced Raf-1 and CR3[YY340/341DD] from 14-3-3, was found to substantially reduce catalytic activity. Taken together, our results support a model of Raf regulation in which the activity of the Raf-1 catalytic domain is directly upregulated by phosphorylation, following relief of inhibition by the N-terminal regulatory domain upon Ras-GTP binding. Moreover, the presence of serine 621 in the free catalytic fragment is required for full CR3 activation by stimulatory factors, and the continuous presence of 14-3-3 at this site is necessary for retaining activity once the kinase is activated.
- Published
- 2000
4. Cyclooxygenase-2 expression in human pancreatic adenocarcinomas
- Author
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Yip-Schneider, M. T., primary
- Published
- 2000
- Full Text
- View/download PDF
5. Lack of elevated MAP kinase (Erk) activity in pancreatic carcinomas despite oncogenic K-ras expression.
- Author
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Yip-Schneider, M T, primary, Lin, A, additional, Barnard, D, additional, Sweeney, C J, additional, and Marshall, M S, additional
- Published
- 1999
- Full Text
- View/download PDF
6. Comparison of skin closure techniques in patients undergoing open pancreaticoduodenectomy: A single center experience.
- Author
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Flick KF, Simpson RE, Soufi M, Fennerty ML, Yip-Schneider MT, Colgate CL, Ceppa EP, House MG, Zyromski NJ, Nakeeb A, and Schmidt CM
- Subjects
- Aged, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Prognosis, Retrospective Studies, United States epidemiology, Pancreaticoduodenectomy methods, Postoperative Complications epidemiology, Wound Closure Techniques
- Abstract
Background: This study evaluated closure techniques and incisional surgical site complications (SSCs) and incisional surgical site infections (SSIs) after pancreaticoduodenectomy (PD)., Methods: Retrospective review of open PDs from 2015 to 2018 was performed. Outcomes were compared among closure techniques (subcuticular + topical skin adhesive (TSA); staples; subcuticular only). SSCs were defined as abscess, cellulitis, seroma, or fat necrosis. SSIs were defined according to the National Surgical Quality Improvement Program (NSQIP)., Results: Patients with subcuticular + TSA (n = 205) were less likely to develop an incisional SSC (9.8%) compared to staples (n = 139) (20.1%) and subcuticular (n = 74) (16.2%) on univariable analysis (P = 0.024). Multivariable analysis revealed no statistically significant difference in incisional SSC between subcuticular + TSA and subcuticular (P = 0.528); a significant difference remained between subcuticular + TSA and staples (P = 0.014). Unadjusted median length of stay (LOS) (days) was significantly longer for staples (9) vs. subcuticular (8) vs. subcuticular + TSA (7); P < 0.001. Incisional SSIs were evaluated separately according to the NSQIP definition. When comparing rates, the subcuticular + TSA group experienced lower incisional SSIs compared to the other two techniques (4.9% vs. 10.1%, 10.8%). However, this difference was not statistically significant by either univariable or multivariable analysis., Conclusions: Subcuticular suture + TSA reduces the risk of incisional SSCs when compared to staples alone after pancreaticoduodenectomy., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
7. Discussion on: Performance of candidate urinary biomarkers for pancreatic cancer - Correlation with pancreatic cyst malignant progression?
- Author
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Yip-Schneider MT, Soufi M, Carr RA, Flick KF, Wu H, and Schmidt CM
- Subjects
- Biomarkers, Humans, Pancreatic Cyst, Pancreatic Neoplasms
- Published
- 2020
- Full Text
- View/download PDF
8. Cell cycle effects of nonsteroidal anti-inflammatory drugs and enhanced growth inhibition in combination with gemcitabine in pancreatic carcinoma cells.
- Author
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Yip-Schneider MT, Sweeney CJ, Jung SH, Crowell PL, and Marshall MS
- Subjects
- Apoptosis drug effects, Blotting, Western, Cell Cycle Proteins biosynthesis, Cell Division drug effects, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors pharmacology, Deoxycytidine analogs & derivatives, Humans, Isoenzymes biosynthesis, Isoenzymes drug effects, Male, Membrane Proteins, Pancreatic Neoplasms metabolism, Prostaglandin-Endoperoxide Synthases biosynthesis, Prostaglandin-Endoperoxide Synthases drug effects, Sulindac pharmacology, Tumor Cells, Cultured, Gemcitabine, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Cell Cycle drug effects, Deoxycytidine pharmacology, Enzyme Inhibitors pharmacology, Pancreatic Neoplasms pathology
- Abstract
Increased cyclooxygenase-2 (COX-2) expression in human pancreatic adenocarcinomas, as well as the growth-inhibitory effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in vitro, suggests that NSAIDs may be an effective treatment for pancreatic cancer. Gemcitabine is currently the most effective chemotherapeutic drug available for patients with pancreatic cancer, but is only minimally effective against this aggressive disease. Clearly, other treatment options must be identified. To design successful therapeutic strategies involving compounds either alone or in combination with others, it is necessary to understand their mechanism of action. In the present study, we evaluated the effects of three NSAIDs (sulindac, indomethacin, and NS-398) or gemcitabine in two human pancreatic carcinoma cell lines, BxPC-3 (COX-2-positive) and PaCa-2 (COX-2-negative), previously shown to be growth-inhibited by these NSAIDs. Effects on cell cycle and apoptosis were investigated by flow cytometry or Western blotting. Treatment with NSAIDs or gemcitabine altered the cell cycle phase distribution as well as the expression of multiple cell cycle regulatory proteins in both cell lines, but did not induce substantial levels of apoptosis. Furthermore, we demonstrated that the combination of the NSAID sulindac or NS-398 with gemcitabine inhibited cell growth to a greater degree than either compound alone. These results indicate that the antiproliferative effects of NSAIDs and gemcitabine in pancreatic tumor cells are primarily due to inhibition of cell cycle progression rather than direct induction of apoptotic cell death, regardless of COX-2 expression. In addition, NSAIDs in combination with gemcitabine may hold promise in the clinic for the treatment of pancreatic cancer.
- Published
- 2001
9. Pancreatic tumor cells with mutant K-ras suppress ERK activity by MEK-dependent induction of MAP kinase phosphatase-2.
- Author
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Yip-Schneider MT, Lin A, and Marshall MS
- Subjects
- Animals, Blotting, Western, Carcinoma enzymology, Cell Line, Down-Regulation, Dual-Specificity Phosphatases, Enzyme Inhibitors pharmacology, Humans, Kinetics, Mitogen-Activated Protein Kinase Phosphatases, Pancreatic Neoplasms enzymology, Phosphorylation drug effects, Protein Phosphatase 2, Rats, Signal Transduction, Time Factors, Tumor Cells, Cultured, Up-Regulation, Vanadates pharmacology, Carcinoma genetics, Gene Expression Regulation, Enzymologic, Genes, ras genetics, Mitogen-Activated Protein Kinase Kinases metabolism, Mitogen-Activated Protein Kinases metabolism, Mutation, Pancreatic Neoplasms genetics, Protein Tyrosine Phosphatases metabolism
- Abstract
Activating mutations within the K-ras gene occur in a high percentage of human pancreatic carcinomas. We reported previously that the presence of oncogenic, activated K-ras in human pancreatic carcinoma cell lines did not result in constitutive activation of the extracellular signal-regulated kinases (ERK1 and ERK2). In the present study, we further characterized the ERK signaling pathway in pancreatic tumor cell lines in order to determine whether the ERK pathway is subject to a compensatory downregulation. We found that the attenuation of serum-induced ERK activation was not due to a delay in the kinetics of ERK phosphorylation. Treatment with the tyrosine phosphatase inhibitor orthovanadate increased the level of ERK phosphorylation, implicating a vanadate-sensitive tyrosine phosphatase in the negative regulation of ERK. Furthermore, expression of a dual specificity phosphatase capable of inactivating ERK known as mitogen-activated protein (MAP) kinase phosphatase-2 (MKP-2) was elevated in most of the pancreatic tumor cell lines and correlated with the presence of active MAP kinase kinase (MEK). Taken together, these results suggest that pancreatic tumor cells expressing oncogenic K-ras compensate, in part, by upregulating the expression of MKP-2 to repress the ERK signaling pathway., (Copyright 2001 Academic Press.)
- Published
- 2001
- Full Text
- View/download PDF
10. Regulation of the Raf-1 kinase domain by phosphorylation and 14-3-3 association.
- Author
-
Yip-Schneider MT, Miao W, Lin A, Barnard DS, Tzivion G, and Marshall MS
- Subjects
- 14-3-3 Proteins, Animals, Binding, Competitive, COS Cells, Catalytic Domain, Enzyme Activation drug effects, Mutation genetics, Oncogene Protein pp60(v-src) genetics, Oncogene Protein pp60(v-src) metabolism, Peptide Fragments chemistry, Peptide Fragments metabolism, Phosphorylation, Phosphoserine metabolism, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins c-raf genetics, Tetradecanoylphorbol Acetate pharmacology, Tyrosine 3-Monooxygenase genetics, Proto-Oncogene Proteins c-raf chemistry, Proto-Oncogene Proteins c-raf metabolism, Tyrosine 3-Monooxygenase metabolism
- Abstract
The Raf-1 kinase domain is kept in an inactive state by the N-terminal regulatory domain. Activation of the kinase domain occurs following release from the N-terminal repression and possible catalytic upregulation. To distinguish the regulatory mechanisms that directly influence the catalytic activity of the enzyme from those which act through the inhibitory domain, the catalytic domain of Raf-1 (CR3) was expressed in COS-7 cells. The role of phosphorylation in the direct regulation of this domain was determined by substituting non-phosphorylatable amino acids for known serine and tyrosine phosphorylation sites. The intrinsic activity of each mutant protein was determined as well as stimulation by v-Src and phorbol esters. Both v-Src and phorbol esters were potent activators of CR3, requiring the serine 338/339 (p21-activated protein kinase, Pak) and tyrosine 340/341 (Src) phosphorylation sites for full stimulation of CR3. In contrast, loss of the serine 497/499 protein kinase C phosphorylation sites had little effect on CR3 activation by either v-Src or phorbol esters. Loss of serine 621, a 14-3-3 adaptor-protein-binding site, prevented activation of CR3 by v-Src or phorbol esters and partially decreased the high basal activity of the kinase fragment. When co-expressed in COS-7 cells, 14-3-3 associated strongly with full-length Raf-1, weakly with wild-type CR3 and not at all with the A621 and D621 CR3 mutants. The role of 14-3-3 in maintaining the activity of the catalytic domain of Raf-1 was investigated further by performing peptide-competition studies with wild-type CR3, wild-type CR3 and v-Src or constitutively active CR3 (CR3[YY340/341DD]). In each case, incubation of the proteins with a phosphoserine-621 Raf-1 peptide, which we show displaced Raf-1 and CR3[YY340/341DD] from 14-3-3, was found to substantially reduce catalytic activity. Taken together, our results support a model of Raf regulation in which the activity of the Raf-1 catalytic domain is directly upregulated by phosphorylation, following relief of inhibition by the N-terminal regulatory domain upon Ras-GTP binding. Moreover, the presence of serine 621 in the free catalytic fragment is required for full CR3 activation by stimulatory factors, and the continuous presence of 14-3-3 at this site is necessary for retaining activity once the kinase is activated.
- Published
- 2000
- Full Text
- View/download PDF
11. Transcriptional induction of pim-1 protein kinase gene expression by interferon gamma and posttranscriptional effects on costimulation with steel factor.
- Author
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Yip-Schneider MT, Horie M, and Broxmeyer HE
- Subjects
- Base Sequence, Binding Sites genetics, Drug Synergism, Gene Expression drug effects, Humans, Leukemia metabolism, Molecular Sequence Data, Promoter Regions, Genetic genetics, Protein Serine-Threonine Kinases biosynthesis, Protein Serine-Threonine Kinases genetics, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins c-pim-1, RNA, Messenger biosynthesis, Recombinant Proteins, Stem Cell Factor, Transcription, Genetic drug effects, Tumor Cells, Cultured, Hematopoietic Cell Growth Factors pharmacology, Interferon-gamma pharmacology, Proto-Oncogene Proteins biosynthesis
- Abstract
Steel factor (SLF) synergizes with interferon gamma (IFN gamma) to stimulate proliferation of the human factor-dependent cell line MO7e. We examined the effects of IFN gamma and SLF treatment, alone or in combination, on the expression of a 33-kD cytoplasmic protein serine/threonine kinase designated pim-1 whose expression has been closely associated with proliferation induced by related myeloid cytokines. IFN gamma alone, but not SLF, stimulated expression of pim-1 RNA and protein in MO7e cells; compared with IFN gamma alone, costimulation with IFN gamma and SLF resulted in a twofold to threefold increase in pim-1 message and protein expression, correlating with synergistic effects on cell proliferation. Both IFN gamma and IFN gamma/SLF induced pim-1 mRNA in the absence of de novo protein synthesis. Nuclear run-on assays showed that, although IFN gamma alone increased the rate of pim-1 gene transcription, costimulation with IFN gamma and SLF did not further potentiate this effect; however, the stability of pim-1 message was significantly enhanced in the presence of both cytokines. An IFN gamma-responsive element within the 5' flanking region of the pim-1 gene that could confer IFN gamma responsiveness on a heterologous promoter was identified. This sequence, designated PMGAS, formed a specific complex with Stat (signal transducers and activators of transcription) 1 alpha (the p91 subunit of the transcription factor ISGF3 [interferon-stimulated gene factor 3]) in IFN gamma-treated cell extracts, suggesting that the transcriptional effects of IFN gamma on pim-1 expression may be mediated by Stat 1 alpha.
- Published
- 1995
12. Characterization of interleukin-7-induced changes in tyrosine phosphorylation and c-myc gene expression in normal human T cells.
- Author
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Yip-Schneider MT, Horie M, and Broxmeyer HE
- Subjects
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Blotting, Northern, Cell Division, Humans, Immunoblotting, Isoquinolines pharmacology, Molecular Weight, Phosphorylation, Phosphotyrosine, Piperazines pharmacology, Protein Kinase Inhibitors, Protein Kinases metabolism, Signal Transduction, T-Lymphocytes cytology, Tetradecanoylphorbol Acetate pharmacology, Transcription, Genetic, Tyrosine metabolism, Gene Expression drug effects, Genes, myc, Interleukin-7 pharmacology, Phosphoproteins metabolism, T-Lymphocytes metabolism, Tyrosine analogs & derivatives
- Abstract
Interleukin-7 (IL-7) is a growth factor involved in regulating lymphopoiesis. We have chosen to study the signal transduction pathway of IL-7 in normal human peripheral blood T lymphocytes. Two early events that occur as a consequence of specific ligand-receptor interaction were examined: activation of protein tyrosine kinases and induction of primary response gene expression. Following treatment of human peripheral blood T cells with IL-7, four cellular proteins with relative molecular weights of 95- (doublet), 105-, and 130-kd were rapidly tyrosine phosphorylated as detected by immunoblotting with an antiphosphotyrosine monoclonal antibody (MAB). The 105-kd tyrosine-phosphorylated protein was membrane-associated after IL-7 stimulation. Treatment of human peripheral blood T cells with IL-7 enhanced expression of the primary response gene c-myc approximately three-fold, as detected by Northern blotting, in the presence or absence of protein synthesis. The rate of c-myc gene transcription increased in the presence of IL-7 and could account for the observed elevation of c-myc RNA levels. In addition, IL-7 treatment induced a slight increase in c-myc message stability. Experiments performed with the protein tyrosine kinase inhibitor genistein and the serine-threonine kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7) demonstrated that these kinases were required for IL-7 enhancement of c-myc expression. Treatment with tetradecanoyl phorbol acetate (TPA), a potent activator of protein kinase C (PKC), in combination with IL-7 induced a level of c-myc expression greater than that elicited by either factor alone, suggesting that TPA and IL-7 utilize cooperative signaling pathways to increase c-myc gene expression.
- Published
- 1993
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