21 results on '"Abruzzo, L V"'
Search Results
2. Extramedullary BCR-ABL1-negative myeloid leukemia in a patient with chronic myeloid leukemia and synchronous cytogenetic abnormalities in Philadelphia-positive and -negative clones during imatinib therapy
- Author
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Quintás-Cardama, A, Kantarjian, H, Abruzzo, L V, and Cortes, J
- Published
- 2007
- Full Text
- View/download PDF
3. A novel translocation t(3;21)(p21;q22) in acute myelogenous leukemia preceding a late-appearing Philadelphia chromosome
- Author
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Quintás-Cardama, A, Abruzzo, L V, Giles, F J, Jorgensen, J, Cortes, J, Sarriera, J E, Kantarjian, H, and Verstovsek, S
- Published
- 2006
- Full Text
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4. Association of 3q21q26 syndrome and late-appearing Philadelphia chromosome in acute myeloid leukemia
- Author
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Quintás-Cardama, A, Gibbons, D L, Cortes, J, Bobadilla, D, Slovak, M L, Kantarjian, H, and Abruzzo, L V
- Published
- 2008
- Full Text
- View/download PDF
5. Th17 and non-Th17 interleukin-17-expressing cells in chronic lymphocytic leukemia: delineation, distribution, and clinical relevance
- Author
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Jain, P., primary, Javdan, M., additional, Feger, F. K., additional, Chiu, P. Y., additional, Sison, C., additional, Damle, R. N., additional, Bhuiya, T. A., additional, Sen, F., additional, Abruzzo, L. V., additional, Burger, J. A., additional, Rosenwald, A., additional, Allen, S. L., additional, Kolitz, J. E., additional, Rai, K. R., additional, Chiorazzi, N., additional, and Sherry, B., additional
- Published
- 2011
- Full Text
- View/download PDF
6. Cytokine-induced gene expression of interleukin-8 in human transitional cell carcinomas and renal cell carcinomas
- Author
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Abruzzo, L. V., Thornton, A. J., Liebert, M., Grossman, H. B., Evanoff, H., Westwick, J., Strieter, R. M., and Kunkel, S. L.
- Subjects
Carcinoma, Transitional Cell ,Urologic Neoplasms ,Base Sequence ,Tumor Necrosis Factor-alpha ,Interleukin-8 ,Molecular Sequence Data ,Enzyme-Linked Immunosorbent Assay ,Blotting, Northern ,Gene Expression Regulation, Neoplastic ,Tumor Cells, Cultured ,Humans ,RNA, Messenger ,RNA, Neoplasm ,Carcinoma, Renal Cell ,Research Article - Abstract
Chemotactic cytokines play a critical role in recruiting leukocytes to sites of tissue injury. Interleukin-8 (IL-8) is a chemotactic cytokine secreted by a variety of cells (eg, monocytes, endothelial cells, fibroblasts) during the inflammatory response. In this report, the authors demonstrate that human transitional cell carcinomas and renal cell carcinomas have the capacity to elaborate IL-8 in response to the inflammatory mediators IL-1 beta and tumor necrosis factor (TNF)-alpha. All cell lines expressed high levels of IL-8 mRNA on stimulation with either IL-1 beta or TNF-alpha, but not lipopolysaccharide; one expressed the gene constitutively. The authors selected one transitional cell carcinoma cell line (UM-UC-9) and one renal cell carcinoma cell line (UM-RC-5) for further study. Both displayed a time- and dose-dependent increase in steady-state levels of IL-8 mRNA in response to IL-1 beta and TNF-alpha. Specific mRNA was detectable by 1 hour after stimulation. Secretion of antigenic IL-8 measured by enzyme-linked immunosorbent assay into culture supernatants reflected the kinetics of mRNA expression. Because heat-inactivated TNF-alpha failed to induce synthesis of IL-8 mRNA, and cycloheximide augmented TNF-alpha-induced synthesis, IL-8 expression appears to be a stimulus-specific primary induction phenomenon. As with other inflammatory mediators whose mRNA contains a 3' AU-rich sequence (eg, IL-2, TNF-alpha), the half-life of IL-8 mRNA was short, less than 1 hour. Our data suggest that secretion of IL-8 by malignant cells may partly account for the inflammatory infiltrates associated with some malignant neoplasms.
- Published
- 1992
7. Association of 3q21q26 syndrome and late-appearing Philadelphia chromosome in acute myeloid leukemia
- Author
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Quintás-Cardama, A, primary, Gibbons, D L, additional, Cortes, J, additional, Bobadilla, D, additional, Slovak, M L, additional, Kantarjian, H, additional, and Abruzzo, L V, additional
- Published
- 2007
- Full Text
- View/download PDF
8. Differences in gene expression between B-cell chronic lymphocytic leukemia and normal B cells: a meta-analysis of three microarray studies
- Author
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Wang, J., primary, Coombes, K. R., additional, Highsmith, W. E., additional, Keating, M. J., additional, and Abruzzo, L. V., additional
- Published
- 2004
- Full Text
- View/download PDF
9. Atypical Multidrug Resistance: Breast Cancer Resistance Protein Messenger RNA Expression in Mitoxantrone-Selected Cell Lines
- Author
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Ross, D. D., primary, Yang, W., additional, Abruzzo, L. V., additional, Dalton, W. S., additional, Schneider, E., additional, Lage, H., additional, Dietel, M., additional, Greenberger, L., additional, Cole, S. P. C., additional, and Doyle, L. A., additional
- Published
- 1999
- Full Text
- View/download PDF
10. Enhancer activity of upstream hypersensitive site 2 of the chicken beta-globin cluster is mediated by GATA sites.
- Author
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Abruzzo, L V, primary and Reitman, M, additional
- Published
- 1994
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- View/download PDF
11. Isochromosome 7q: the primary cytogenetic abnormality in hepatosplenic gammadelta T cell lymphoma.
- Author
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Alonsozana, E L C, Stamberg, J, Kumar, D, Jaffe, E S, Medeiros, L J, Frantz, C, Schiffer, C A, O’Connell, B A, Kerman, S, Stass, S A, Abruzzo, L V, Alonsozana, E L, and O'Connell, B A
- Subjects
LYMPHOMAS ,CHROMOSOME abnormalities - Abstract
Malignant lymphomas often have complex, nonrandom chromosomal abnormalities. Hepatosplenic gammadelta T cell lymphoma (gammadelta TCL) is an unusual post-thymic T cell lymphoma that primarily involves liver and spleen, often in young adult males. Few cases have had cytogenetic analysis. We report a consistent isochromosome 7q [i(7q)] abnormality in three cases of hepatosplenic gammadelta TCL, one with i(7q) as the sole abnormality at presentation. Three patients, 15-, 37- and 65-year-old males, presented with hepatosplenomegaly and fevers. Histopathologic, immunophenotypic, and molecular genetic studies supported the diagnosis. Spleen, liver, and bone marrow contained sinusoidal infiltrates of atypical lymphoid cells of T cell immunophenotype. PCR performed on two cases demonstrated clonal T cell receptor gamma gene rearrangements. Cytogenetic analysis of bone marrow showed i(7q) as the sole abnormality at presentation in one case. The second case showed i(7q) in addition to two normal chromosomes 7, and other structural and numerical abnormalities. The third case showed i(7q) and a deletion in the long arm of chromosome 11. These findings support the proposal that i(7q) represents the primary nonrandom cytogenetic abnormality in hepatosplenic gammadelta TCL, and plays a role in its pathogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 1997
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- View/download PDF
12. Primary follicular large cell lymphoma of the testis in a child.
- Author
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Lu D, Medeiros LJ, Eskenazi AE, and Abruzzo LV
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, B-Lymphocytes chemistry, B-Lymphocytes pathology, Biomarkers, Tumor analysis, Child, Cyclophosphamide administration & dosage, DNA, Neoplasm analysis, Doxorubicin administration & dosage, Humans, Immunohistochemistry, Lymphoma, Follicular chemistry, Lymphoma, Follicular therapy, Male, Neoplasm Proteins analysis, Orchiectomy, Polymerase Chain Reaction, Prednisone administration & dosage, Testicular Neoplasms chemistry, Testicular Neoplasms therapy, Treatment Outcome, Vincristine administration & dosage, Lymphoma, Follicular pathology, Testicular Neoplasms pathology
- Abstract
Primary follicular lymphoma of the testis in childhood is extremely rare. To our knowledge, only 5 cases have been reported to date. We report a case in a 6-year-old boy who presented with painless right scrotal enlargement. Right radical orchiectomy revealed a follicular large cell lymphoma with diffuse areas confined to the testis and epididymis, clinical stage IE. Immunohistochemical stains demonstrated that the neoplastic cells were of B-cell lineage, positive for CD10, CD20, CD79a, and BCL-6. Staining for CD21 accentuated networks of dendritic reticulum cells within the nodules. The cells were negative for BCL-2, p53, and T-cell antigens. There was no evidence of the t(14;18) detected by polymerase chain reaction. The data suggest that follicular lymphoma of the testis in children has a different pathogenesis than follicular lymphoma in adults.
- Published
- 2001
- Full Text
- View/download PDF
13. Primary paratesticular lymphoma: a report of 2 cases and review of literature.
- Author
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Vega F, Medeiros LJ, and Abruzzo LV
- Subjects
- Adult, Biomarkers, Tumor metabolism, Epididymis metabolism, Epididymis surgery, Humans, Immunoenzyme Techniques, Lymphoma, B-Cell metabolism, Lymphoma, B-Cell surgery, Lymphoma, Large B-Cell, Diffuse metabolism, Lymphoma, Large B-Cell, Diffuse surgery, Male, Middle Aged, Spermatic Cord metabolism, Spermatic Cord surgery, Testicular Neoplasms metabolism, Testicular Neoplasms surgery, Epididymis pathology, Lymphoma, B-Cell pathology, Lymphoma, Large B-Cell, Diffuse pathology, Spermatic Cord pathology, Testicular Neoplasms pathology
- Abstract
Non-Hodgkin lymphoma arising in the paratesticular organs without testicular involvement is rare. In most previously reported cases, the classification systems that were used are now outdated and/or immunologic studies were not done. We report the clinical and pathologic features of 2 cases of non-Hodgkin lymphoma arising in the epididymis and the spermatic cord. Patient 1 was a 35-year-old man who presented with a painless scrotal mass. Patient 2 was a 61-year-old man who presented with a right inguinal mass. Orchiectomy performed in both patients revealed a mass confined to the epididymis in patient 1 and to the spermatic cord in patient 2. Histologic examination in both cases revealed diffuse large cell lymphoma, and immunohistochemical studies supported B-cell lineage. Subsequent staging studies showed no other site of disease in patient 1 and an isolated mass anterior to the right psoas muscle in patient 2. Malignant lymphoma involving testicular adnexal structures without involvement of the testis is extremely uncommon. To our knowledge, only 6 cases confined to the epididymis and 12 cases confined to the spermatic cord have been reported previously.
- Published
- 2001
- Full Text
- View/download PDF
14. Identifying differentially expressed genes in cDNA microarray experiments.
- Author
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Baggerly KA, Coombes KR, Hess KR, Stivers DN, Abruzzo LV, and Zhang W
- Subjects
- Analysis of Variance, Computational Biology, Glioma genetics, Humans, Models, Statistical, Regression Analysis, Tumor Cells, Cultured, Gene Expression Profiling statistics & numerical data, Oligonucleotide Array Sequence Analysis statistics & numerical data
- Abstract
A major goal of microarray experiments is to determine which genes are differentially expressed between samples. Differential expression has been assessed by taking ratios of expression levels of different samples at a spot on the array and flagging spots (genes) where the magnitude of the fold difference exceeds some threshold. More recent work has attempted to incorporate the fact that the variability of these ratios is not constant. Most methods are variants of Student's t-test. These variants standardize the ratios by dividing by an estimate of the standard deviation of that ratio; spots with large standardized values are flagged. Estimating these standard deviations requires replication of the measurements, either within a slide or between slides, or the use of a model describing what the standard deviation should be. Starting from considerations of the kinetics driving microarray hybridization, we derive models for the intensity of a replicated spot, when replication is performed within and between arrays. Replication within slides leads to a beta-binomial model, and replication between slides leads to a gamma-Poisson model. These models predict how the variance of a log ratio changes with the total intensity of the signal at the spot, independent of the identity of the gene. Ratios for genes with a small amount of total signal are highly variable, whereas ratios for genes with a large amount of total signal are fairly stable. Log ratios are scaled by the standard deviations given by these functions, giving model-based versions of Studentization. An example is given.
- Published
- 2001
- Full Text
- View/download PDF
15. Atypical multidrug resistance: breast cancer resistance protein messenger RNA expression in mitoxantrone-selected cell lines.
- Author
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Ross DD, Yang W, Abruzzo LV, Dalton WS, Schneider E, Lage H, Dietel M, Greenberger L, Cole SP, and Doyle LA
- Subjects
- Blotting, Northern, Blotting, Southern, Breast Neoplasms genetics, Colonic Neoplasms drug therapy, Colonic Neoplasms metabolism, Fibrosarcoma drug therapy, Fibrosarcoma metabolism, Humans, Multiple Myeloma drug therapy, Multiple Myeloma metabolism, Neoplasm Proteins genetics, RNA, Messenger analysis, RNA, Neoplasm analysis, Stomach Neoplasms drug therapy, Stomach Neoplasms metabolism, Tumor Cells, Cultured, Up-Regulation, Antineoplastic Agents pharmacology, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Drug Resistance, Multiple genetics, Drug Resistance, Neoplasm genetics, Gene Expression Regulation, Neoplastic, Mitoxantrone pharmacology, Neoplasm Proteins biosynthesis
- Abstract
Background: Human cancer cell lines grown in the presence of the cytotoxic agent mitoxantrone frequently develop resistance associated with a reduction in intracellular drug accumulation without increased expression of the known drug resistance transporters P-glycoprotein and multidrug resistance protein (also known as multidrug resistance-associated protein). Breast cancer resistance protein (BCRP) is a recently described adenosine triphosphate-binding cassette transporter associated with resistance to mitoxantrone and anthracyclines. This study was undertaken to test the prevalence of BCRP overexpression in cell lines selected for growth in the presence of mitoxantrone., Methods: Total cellular RNA or poly A+ RNA and genomic DNA were isolated from parental and drug-selected cell lines. Expression of BCRP messenger RNA (mRNA) and amplification of the BCRP gene were analyzed by northern and Southern blot hybridization, respectively., Results: A variety of drug-resistant human cancer cell lines derived by selection with mitoxantrone markedly overexpressed BCRP mRNA; these cell lines included sublines of human breast carcinoma (MCF-7), colon carcinoma (S1 and HT29), gastric carcinoma (EPG85-257), fibrosarcoma (EPF86-079), and myeloma (8226) origins. Analysis of genomic DNA from BCRP-overexpressing MCF-7/MX cells demonstrated that the BCRP gene was also amplified in these cells., Conclusions: Overexpression of BCRP mRNA is frequently observed in multidrug-resistant cell lines selected with mitoxantrone, suggesting that BCRP is likely to be a major cellular defense mechanism elicited in response to exposure to this drug. It is likely that BCRP is the putative "mitoxantrone transporter" hypothesized to be present in these cell lines.
- Published
- 1999
- Full Text
- View/download PDF
16. A multidrug resistance transporter from human MCF-7 breast cancer cells.
- Author
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Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK, and Ross DD
- Subjects
- ATP Binding Cassette Transporter, Subfamily G, Member 2, ATP-Binding Cassette Transporters biosynthesis, ATP-Binding Cassette Transporters chemistry, Adenosine Triphosphate metabolism, Amino Acid Sequence, Animals, Breast Neoplasms, Cell Survival drug effects, Cloning, Molecular, DNA Primers, Female, Gene Library, Humans, Molecular Sequence Data, Phylogeny, RNA, Messenger genetics, Recombinant Proteins biosynthesis, Recombinant Proteins chemistry, Reverse Transcriptase Polymerase Chain Reaction, Software, Transfection, Tumor Cells, Cultured, ATP-Binding Cassette Transporters genetics, Antineoplastic Agents toxicity, Daunorubicin pharmacokinetics, Drug Resistance, Multiple, Neoplasm Proteins, Transcription, Genetic
- Abstract
MCF-7/AdrVp is a multidrug-resistant human breast cancer subline that displays an ATP-dependent reduction in the intracellular accumulation of anthracycline anticancer drugs in the absence of overexpression of known multidrug resistance transporters such as P glycoprotein or the multidrug resistance protein. RNA fingerprinting led to the identification of a 2.4-kb mRNA that is overexpressed in MCF-7/AdrVp cells relative to parental MCF-7 cells. The mRNA encodes a 655-aa [corrected] member of the ATP-binding cassette superfamily of transporters that we term breast cancer resistance protein (BCRP). Enforced expression of the full-length BCRP cDNA in MCF-7 breast cancer cells confers resistance to mitoxantrone, doxorubicin, and daunorubicin, reduces daunorubicin accumulation and retention, and causes an ATP-dependent enhancement of the efflux of rhodamine 123 in the cloned transfected cells. BCRP is a xenobiotic transporter that appears to play a major role in the multidrug resistance phenotype of MCF-7/AdrVp human breast cancer cells.
- Published
- 1998
- Full Text
- View/download PDF
17. Posttransplantation lymphoproliferative disorder associated with OKT3 and decreased antiviral prophylaxis in pancreas transplant recipients.
- Author
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Keay S, Oldach D, Wiland A, Klassen D, Schweitzer E, Abruzzo LV, Kumar D, and Bartlett S
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- Acyclovir administration & dosage, Adult, Antiviral Agents administration & dosage, Antiviral Agents therapeutic use, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Ganciclovir administration & dosage, Humans, Immunosuppressive Agents therapeutic use, Lymphoproliferative Disorders chemically induced, Lymphoproliferative Disorders drug therapy, Male, Muromonab-CD3 therapeutic use, Treatment Outcome, Immunosuppressive Agents adverse effects, Lymphoproliferative Disorders etiology, Muromonab-CD3 adverse effects, Pancreas Transplantation adverse effects
- Abstract
Between September 1994 and October 1995, we diagnosed and treated four cases of early onset posttransplantation lymphoproliferative disorder (PTLD) occurring within 62 days of pancreas transplantation. The development of PTLD was associated with both a significantly higher total muromonab-CD3 (OKT3) dose and a lack of ganciclovir/acyclovir prophylaxis, but it was not associated with the total dose of antithymocyte globulin or cytomegalovirus serostatus. All four patients were treated aggressively and survived without evidence of recurrent PTLD more than 1.5 years later. We conclude that the use of a high total dose of OKT3 puts pancreas transplant recipients at increased risk for early onset PTLD, while ganciclovir/acyclovir prophylaxis may help to prevent this disorder; however, if early onset PTLD does occur in these patients, aggressive therapy can lead to a favorable outcome.
- Published
- 1998
- Full Text
- View/download PDF
18. B-cell lymphoma after angioimmunoblastic lymphadenopathy: a case with oligoclonal gene rearrangements associated with Epstein-Barr virus.
- Author
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Abruzzo LV, Schmidt K, Weiss LM, Jaffe ES, Medeiros LJ, Sander CA, and Raffeld M
- Subjects
- Blotting, Southern, Clone Cells, DNA, Viral analysis, Genes, Immunoglobulin, Herpesvirus 4, Human genetics, Humans, Immunoblastic Lymphadenopathy pathology, Immunophenotyping, In Situ Hybridization, Lymph Nodes pathology, Lymphoma, B-Cell immunology, Male, Middle Aged, RNA, Viral analysis, Gene Rearrangement, B-Lymphocyte, Herpesvirus 4, Human pathogenicity, Immunoblastic Lymphadenopathy complications, Lymphoma, B-Cell genetics, Tumor Virus Infections complications
- Abstract
We describe a patient with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), who subsequently developed large-cell immunoblastic lymphoma of B-cell immunophenotype. At the time of the initial diagnosis, histologic examination of an inguinal lymph node showed typical features of AILD, and there was no evidence of a monoclonal B-cell population by immunohistochemical analysis. In situ hybridization and Southern blot analysis for Epstein-Barr virus (EBV) were negative. At autopsy 2 years later, the patient had widespread lymph node and organ involvement by large-cell immunoblastic lymphoma of B-cell immunophenotype. Southern blot analysis performed on DNA extracted from lymph nodes, liver, and spleen showed two patterns of Ig heavy chain and kappa light chain gene rearrangements. The T-cell receptor beta chain gene was in the germline configuration. Analysis with an EBV terminal repeat region probe showed two clonal populations that paralleled the Ig gene rearrangement studies. Double-labeling immunohistochemistry and in situ hybridization confirmed the presence of EBV within the neoplastic B cells. The data support the hypothesis that EBV was not etiologically related to AILD in this case, and that EBV proliferation may occur after the onset of the disease. Further, the data suggest that some B-cell lymphomas that arise in the setting of AILD resemble EBV-associated B-cell lymphomas that arise in other immunodeficiency states.
- Published
- 1993
19. Cytokine-induced gene expression of interleukin-8 in human transitional cell carcinomas and renal cell carcinomas.
- Author
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Abruzzo LV, Thornton AJ, Liebert M, Grossman HB, Evanoff H, Westwick J, Strieter RM, and Kunkel SL
- Subjects
- Base Sequence, Blotting, Northern, Enzyme-Linked Immunosorbent Assay, Humans, Interleukin-8 genetics, Interleukin-8 metabolism, Molecular Sequence Data, RNA, Messenger drug effects, RNA, Neoplasm drug effects, Tumor Cells, Cultured, Carcinoma, Renal Cell metabolism, Carcinoma, Transitional Cell metabolism, Gene Expression Regulation, Neoplastic drug effects, Interleukin-8 biosynthesis, Tumor Necrosis Factor-alpha pharmacology, Urologic Neoplasms metabolism
- Abstract
Chemotactic cytokines play a critical role in recruiting leukocytes to sites of tissue injury. Interleukin-8 (IL-8) is a chemotactic cytokine secreted by a variety of cells (eg, monocytes, endothelial cells, fibroblasts) during the inflammatory response. In this report, the authors demonstrate that human transitional cell carcinomas and renal cell carcinomas have the capacity to elaborate IL-8 in response to the inflammatory mediators IL-1 beta and tumor necrosis factor (TNF)-alpha. All cell lines expressed high levels of IL-8 mRNA on stimulation with either IL-1 beta or TNF-alpha, but not lipopolysaccharide; one expressed the gene constitutively. The authors selected one transitional cell carcinoma cell line (UM-UC-9) and one renal cell carcinoma cell line (UM-RC-5) for further study. Both displayed a time- and dose-dependent increase in steady-state levels of IL-8 mRNA in response to IL-1 beta and TNF-alpha. Specific mRNA was detectable by 1 hour after stimulation. Secretion of antigenic IL-8 measured by enzyme-linked immunosorbent assay into culture supernatants reflected the kinetics of mRNA expression. Because heat-inactivated TNF-alpha failed to induce synthesis of IL-8 mRNA, and cycloheximide augmented TNF-alpha-induced synthesis, IL-8 expression appears to be a stimulus-specific primary induction phenomenon. As with other inflammatory mediators whose mRNA contains a 3' AU-rich sequence (eg, IL-2, TNF-alpha), the half-life of IL-8 mRNA was short, less than 1 hour. Our data suggest that secretion of IL-8 by malignant cells may partly account for the inflammatory infiltrates associated with some malignant neoplasms.
- Published
- 1992
20. Homeostasis of the antibody response: immunoregulation by NK cells.
- Author
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Abruzzo LV and Rowley DA
- Subjects
- Animals, Antibody-Producing Cells immunology, Cells, Cultured, Homeostasis, Killer Cells, Natural radiation effects, Lymphocyte Cooperation, Mice, Poly I-C immunology, Spleen immunology, Antibody Formation, Killer Cells, Natural immunology, Lymphocytes immunology
- Abstract
When injected into mice, the synthetic double-stranded polynucleotide poly(inosinic) X poly(cytidylic) acid induces high natural killer (NK) cell activity within 4 to 12 hours. Induction of NK activity in mice immunized 2 or 3 days previously, or the addition of NK cells to cultures immunized in vitro 2 or 3 days previously, promotes early termination of the ongoing primary immunoglobulin M antibody response. A target for NK cells is a population of accessory cells that has interacted with antigen and is necessary for sustaining the antibody response. The inference is strong that NK cells induced normally by immunization also terminate the usual antibody response in vivo by elimination of antigen-exposed accessory cells.
- Published
- 1983
- Full Text
- View/download PDF
21. In vitro and in vivo interaction between murine fibrosarcoma cells and natural killer cells.
- Author
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Laybourn KA, Hiserodt JC, Abruzzo LV, and Varani J
- Subjects
- Animals, Antibodies, Monoclonal, Cell Line, Cytotoxicity, Immunologic, Glycosphingolipids immunology, Laminin physiology, Mice, Poly I-C immunology, Receptors, Immunologic metabolism, Receptors, Laminin, Fibrosarcoma immunology, G(M1) Ganglioside, Immunity, Innate, Killer Cells, Natural immunology, Lung Neoplasms immunology
- Abstract
Murine fibrosarcoma cells were examined for sensitivity to killing by natural killer (NK) and natural cytotoxic lymphocytes from mouse spleens. These tumor cell lines were sensitive to killing by effector cells which were nonadherent to plastic or nylon wool, Thy-1 negative, asialo-GM1 negative, and present in the spleens of beige mice, nude mice, and A/J mice, as well as in the spleens of normal syngeneic and allogeneic control mice. This indicates that the cytotoxic effects were due to natural cytotoxic lymphocytes rather than to NK lymphocytes, T-cells, or macrophages. Although the fibrosarcoma cells were not killed in vitro by endogenous NK cells, these tumor cells were able to "cold target" compete for Yac-1 (an NK-sensitive target) killing and to bind to asialo-GM1-positive, nonadherent spleen lymphocytes in a target cell binding assay. This suggests that the fibrosarcoma cells were recognized by NK cells. In addition, these cell lines were killed in a 4-h NK cytotoxicity assay by polyinosinic-polycytidylic acid-activated effector lymphocytes. The interaction between NK cells and the murine fibrosarcoma cells may have in vivo significance. When syngeneic mice were treated with anti-asialo-GM1 serum to eliminate NK activity and then given i.v. injections of the fibrosarcoma cells, many more lung tumors developed than in control animals. The structural basis for the recognition of the murine fibrosarcoma cells by the NK effector cells is not known. However, laminin may be involved. When the fibrosarcoma cells, which have receptors for the laminin molecule, were preincubated with laminin, they were reduced in their ability to compete for the killing of Yac-1 cells by the NK effectors and had reduced capacity to bind to NK cells in a target cell binding assay.
- Published
- 1986
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