7 results on '"Glinsmann-Gibson BJ"'
Search Results
2. Molecular classification of primary mediastinal large B-cell lymphoma using routinely available tissue specimens.
- Author
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Mottok A, Wright G, Rosenwald A, Ott G, Ramsower C, Campo E, Braziel RM, Delabie J, Weisenburger DD, Song JY, Chan WC, Cook JR, Fu K, Greiner T, Smeland E, Holte H, Savage KJ, Glinsmann-Gibson BJ, Gascoyne RD, Staudt LM, Jaffe ES, Connors JM, Scott DW, Steidl C, and Rimsza LM
- Subjects
- Cohort Studies, Gene Expression Regulation, Neoplastic, Humans, Lymphoma, Large B-Cell, Diffuse classification, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Non-Hodgkin classification, Lymphoma, Non-Hodgkin genetics, Mediastinal Neoplasms classification, Mediastinal Neoplasms genetics, Mediastinum pathology, Paraffin Embedding, Gene Expression Profiling, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Non-Hodgkin diagnosis, Mediastinal Neoplasms diagnosis
- Abstract
Primary mediastinal large B-cell lymphoma (PMBCL) is recognized as a distinct entity in the World Health Organization classification. Currently, the diagnosis relies on consensus of histopathology, clinical variables, and presentation, giving rise to diagnostic inaccuracy in routine practice. Previous studies have demonstrated that PMBCL can be distinguished from subtypes of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures. However, requirement of fresh-frozen biopsy material has precluded the transfer of gene expression-based assays to the clinic. Here, we developed a robust and accurate molecular classification assay (Lymph3Cx) for the distinction of PMBCL from DLBCL subtypes based on gene expression measurements in formalin-fixed, paraffin-embedded tissue. A probabilistic model accounting for classification error, comprising 58 gene features, was trained on 68 cases of PMBCL and DLBCL. Performance of the model was subsequently evaluated in an independent validation cohort of 158 cases and showed high agreement of the Lymph3Cx molecular classification with the clinicopathological diagnosis of an expert panel (frank misclassification rate, 3.8%). Furthermore, we demonstrate reproducibility of the assay with 100% concordance of subtype assignments at 2 independent laboratories. Future studies will determine Lymph3Cx's utility for routine diagnostic purposes and therapeutic decision making., (© 2018 by The American Society of Hematology.)
- Published
- 2018
- Full Text
- View/download PDF
3. Determining cell-of-origin subtypes of diffuse large B-cell lymphoma using gene expression in formalin-fixed paraffin-embedded tissue.
- Author
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Scott DW, Wright GW, Williams PM, Lih CJ, Walsh W, Jaffe ES, Rosenwald A, Campo E, Chan WC, Connors JM, Smeland EB, Mottok A, Braziel RM, Ott G, Delabie J, Tubbs RR, Cook JR, Weisenburger DD, Greiner TC, Glinsmann-Gibson BJ, Fu K, Staudt LM, Gascoyne RD, and Rimsza LM
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Biopsy, Female, Fixatives, Formaldehyde, Humans, Male, Middle Aged, Paraffin Embedding, Tissue Banks, Transcriptome, Young Adult, Cell Lineage genetics, Gene Expression Regulation, Neoplastic, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
The assignment of diffuse large B-cell lymphoma into cell-of-origin (COO) groups is becoming increasingly important with the emergence of novel therapies that have selective biological activity in germinal center B cell-like or activated B cell-like groups. The Lymphoma/Leukemia Molecular Profiling Project's Lymph2Cx assay is a parsimonious digital gene expression (NanoString)-based test for COO assignment in formalin-fixed paraffin-embedded tissue (FFPET). The 20-gene assay was trained using 51 FFPET biopsies; the locked assay was then validated using an independent cohort of 68 FFPET biopsies. Comparisons were made with COO assignment using the original COO model on matched frozen tissue. In the validation cohort, the assay was accurate, with only 1 case with definitive COO being incorrectly assigned, and robust, with >95% concordance of COO assignment between 2 independent laboratories. These qualities, along with the rapid turnaround time, make Lymph2Cx attractive for implementation in clinical trials and, ultimately, patient management.
- Published
- 2014
- Full Text
- View/download PDF
4. A model of sensitivity and resistance to histone deacetylase inhibitors in diffuse large B cell lymphoma: Role of cyclin-dependent kinase inhibitors.
- Author
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Tula-Sanchez AA, Havas AP, Alonge PJ, Klein ME, Doctor SR, Pinkston W, Glinsmann-Gibson BJ, Rimsza LM, and Smith CL
- Subjects
- Apoptosis, Cell Line, Tumor drug effects, Cell Proliferation drug effects, Drug Resistance, Neoplasm, Drug Screening Assays, Antitumor, G2 Phase Cell Cycle Checkpoints, Gene Expression Regulation, Neoplastic drug effects, Humans, Inhibitory Concentration 50, Lymphoma, Large B-Cell, Diffuse metabolism, Phosphorylation, Protein Processing, Post-Translational drug effects, Proto-Oncogene Proteins c-bcl-2 metabolism, Proto-Oncogene Proteins c-myc metabolism, Retinoblastoma Protein metabolism, Up-Regulation drug effects, Antineoplastic Agents pharmacology, Cyclin-Dependent Kinase Inhibitor p21 physiology, Cyclin-Dependent Kinase Inhibitor p27 physiology, Histone Deacetylase Inhibitors pharmacology, Hydroxamic Acids pharmacology, Lymphoma, Large B-Cell, Diffuse drug therapy, Sulfonamides pharmacology
- Abstract
Diffuse large B cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin lymphoma. While the initial treatment strategy is highly effective, relapse occurs in 40% of cases. Histone deacetylase inhibitors (HDACi) are a promising class of anti-cancer drugs but their single agent efficacy against relapsed DLBCL has been variable, ranging from few complete/partial responses to some stable disease. However, most patients showed no response to HDACi monotherapy for unknown reasons. Here we show that sensitivity and resistance to the hydroxamate HDACi, PXD101, can be modeled in DLBCL cell lines. Sensitivity is characterized by G 2/M arrest and apoptosis and resistance by reversible G 1 growth arrest. These responses to PXD101 are independent of several negative prognostic indicators such as DLBCL subtype, BCL2 and MYC co-expression, and p53 mutation, suggesting that HDACi might be used effectively against highly aggressive DLBCL tumors if they are combined with other therapeutics that overcome HDACi resistance. Our investigation of mechanisms underlying HDACi resistance showed that cyclin-dependent kinase inhibitors (CKIs), p21 and p27, are upregulated by PXD101 in a sustained fashion in resistant cell lines concomitant with decreased activity of the cyclin E/cdk2 complex and decreased Rb phosphorylation. PXD101 treatment results in increased association of CKI with the cyclin E/cdk2 complex in resistant cell lines but not in a sensitive line, indicating that the CKIs play a key role in G 1 arrest. The results suggest several treatment strategies that might increase the efficacy of HDACi against aggressive DLBCL.
- Published
- 2013
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5. Partial plasma cell differentiation as a mechanism of lost major histocompatibility complex class II expression in diffuse large B-cell lymphoma.
- Author
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Wilkinson ST, Vanpatten KA, Fernandez DR, Brunhoeber P, Garsha KE, Glinsmann-Gibson BJ, Grogan TM, Teruya-Feldstein J, and Rimsza LM
- Subjects
- Analysis of Variance, Antigens, CD20 genetics, Antigens, CD20 metabolism, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, HLA-DR Antigens genetics, HLA-DR Antigens metabolism, Histocompatibility Antigens Class II metabolism, Humans, Immunohistochemistry, Interferon Regulatory Factors genetics, Interferon Regulatory Factors metabolism, Lymphoma, B-Cell genetics, Lymphoma, B-Cell metabolism, Lymphoma, Large B-Cell, Diffuse metabolism, Oligonucleotide Array Sequence Analysis, Plasma Cells pathology, Positive Regulatory Domain I-Binding Factor 1, Regulatory Factor X Transcription Factors, Repressor Proteins genetics, Repressor Proteins metabolism, Transcription Factors genetics, Transcription Factors metabolism, X-Box Binding Protein 1, Cell Differentiation genetics, Histocompatibility Antigens Class II genetics, Lymphoma, Large B-Cell, Diffuse genetics, Plasma Cells metabolism
- Abstract
Loss of major histocompatibility complex class II (MHC II) expression is associated with poor patient outcome in diffuse large B-cell lymphoma (DLBCL). As MHC II molecules are lost with plasmacytic differentiation in normal cells, we asked whether MHC II loss in DLBCL is associated with an altered differentiation state. We used gene expression profiling, quantum dots, and immunohistochemistry to study the relationship between MHC II and plasma cell markers in DLBCL and plasmablastic lymphoma (PBL). Results demonstrate that MHC II(-) DLBCL immunophenotypically overlap with PBL and demonstrate an inverse correlation between MHC II and plasma cell markers MUM1, PRDM1/Blimp1, and XBP1s. In addition, MHC II expression is significantly higher in germinal center-DLBCL than activated B cell-DLBCL. A minor subset of cases with an unusual pattern of mislocalized punctate MHC II staining and intermediate levels of mRNA is also described. Finally, we show that PBL is negative for MHC II. The results imply a spectrum of MHC II expression that is more frequently diminished in tumors derived from B cells at the later stages of differentiation (with complete loss in PBL). Our observations provide a possible unifying concept that may contribute to the poor outcome reported in all MHC II(-) B-cell tumors.
- Published
- 2012
- Full Text
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6. Cytogenetics and P-glycoprotein (PGP) are independent predictors of treatment outcome in acute myeloid leukemia (AML).
- Author
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Samdani A, Vijapurkar U, Grimm MA, Spier CS, Grogan TM, Glinsmann-Gibson BJ, and List AF
- Subjects
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Analysis of Variance, Antigens, CD34 analysis, Child, Disease-Free Survival, Female, Humans, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute metabolism, Logistic Models, Male, Middle Aged, Multivariate Analysis, Predictive Value of Tests, Remission Induction, Sex Factors, Treatment Outcome, ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism, Chromosome Aberrations, Leukemia, Myeloid, Acute genetics
- Abstract
Clinical and biological features have recognized prognostic significance in acute myeloid leukemia (AML). To evaluate the interaction of these variables and weighted effect on treatment outcome, prognostic variables from 96 previously untreated patients were analyzed for association with expression of the MDR1 gene product P-glycoprotein (Pgp), and effect on response to induction chemotherapy, progression-free survival and overall survival. Multivariate relationships were analyzed using six prognostic variables, including age, cytogenetic pattern, gender, CD34+ surface phenotype, AML type (de novo versus secondary) and Pgp. Univariate comparisons indicate that Pgp (P = 0.0001), cytogenetic pattern (P = 0.0004) and a Cd34+ phenotype (P = 0.0005) are predictive of primary treatment failure, whereas Pgp (P = 0.0001) had the greatest predictive value in multivariate analysis. Only cytogenetic pattern retained prognostic significance (P = 0.0143) for response to induction therapy after adjustment for Pgp. Although all variable except gender were associated with Pgp, specimens harboring the favorable karyotypic abnormalities t(15;17), t(8;21) and inv(16) exclusively lacked Pgp expression. In a multivariate model, both Pgp and cytogenetic pattern predicted response and overall survival, whereas secondary AML and cytogenetic pattern influenced remission duration. These findings indicate that cytogenetic has prognostic relevance that is independent of Pgp, and implies the presence of undefined biological mechanisms affecting chemotherapy resistance.
- Published
- 1996
- Full Text
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7. Regulation of transforming growth factor-alpha mRNA expression in T3M4 human pancreatic carcinoma cells.
- Author
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Glinsmann-Gibson BJ and Korc M
- Subjects
- Dactinomycin pharmacology, Humans, Nucleic Acid Hybridization, Pancreatic Neoplasms genetics, RNA, Messenger drug effects, RNA, Messenger metabolism, RNA, Neoplasm drug effects, RNA, Neoplasm metabolism, Tetradecanoylphorbol Acetate pharmacology, Transforming Growth Factor alpha pharmacology, Tumor Cells, Cultured, Epidermal Growth Factor pharmacology, Gene Expression Regulation, Neoplastic drug effects, Pancreatic Neoplasms metabolism, RNA, Messenger biosynthesis, RNA, Neoplasm biosynthesis, Transforming Growth Factor alpha genetics
- Abstract
Cultured human pancreatic cancer cells produce transforming growth factor-alpha (TGF-alpha), a potent mitogenic polypeptide. In the present study, we investigated the regulation of TGF-alpha mRNA expression in T3M4 human pancreatic carcinoma cells. TGF-alpha mRNA levels were quantitated by densitometric analysis of autoradiographs obtained following hybridization of size-fractionated cytoplasmic RNA with 32P-labeled cRNA coding for human TGF-alpha. There was a twofold increase in TGF-alpha mRNA levels at 2 h following addition of either epidermal growth factor (EGF) or TGF-alpha. However, TGF-alpha mRNA levels declined to near basal levels by 10 h. At 2 h, one-half maximal stimulation of TGF-alpha mRNA levels occurred at 1 nM and maximal stimulation at 4 nM of either EGF or TGF-alpha. The transcriptional inhibitor actinomycin D (Act D) and the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), mimicked the actions of EGF and TGF-alpha. These findings indicate that the regulation of TGF-alpha mRNA expression in T3M4 cells is complex, and is mediated, in part, via the EGF receptor.
- Published
- 1991
- Full Text
- View/download PDF
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