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Friedman, Daphne Ruth

Overview:

My area of expertise is in leukemias and lymphomas, including Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. My research interests are focused on improving treatment options for patients with hematologic malignancies, through laboratory and clinical research.  I am also a staff physician at the Durham VA Medical Center, and am deeply committed to expanding treatment options for veterans, including working on clinical trials for multiple myeloma, prostate cancer, and lung cancer at the Durham VA.

Positions:

Associate Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2002

M.D. — University of Maryland, College Park

Medical Resident, Medicine

University of Maryland, College Park

Fellow In Hematology Oncology, Medicine

Duke University

Publications:

Lipids and Their Effects in Chronic Lymphocytic Leukemia.

Authors
Friedman, DR
MLA Citation
Friedman, DR. "Lipids and Their Effects in Chronic Lymphocytic Leukemia." EBioMedicine 15 (February 2017): 2-3. (Letter)
PMID
27988133
Source
epmc
Published In
EBioMedicine
Volume
15
Publish Date
2017
Start Page
2
End Page
3
DOI
10.1016/j.ebiom.2016.12.001

Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes: a multi-institutional study.

Monocyte-derived cells, constituents of the cancer microenvironment, support chronic lymphocytic leukemia (CLL) cell survival in vitro via direct cell-cell interaction and secreted factors. We hypothesized that circulating absolute monocyte count (AMC) reflects the monocyte-derived cells in the microenvironment, and that higher AMC is associated with increased CLL cell survival in vivo and thus inferior CLL patient outcomes. We assessed the extent to which AMC at diagnosis of CLL is correlated with clinical outcomes, and whether this information adds to currently used prognostic markers. We evaluated AMC, clinically used prognostic markers, and time to event data from 1,168 CLL patients followed at the Mayo Clinic, the Duke University Medical Center, and the Durham VA Medical Center. Elevated AMC was significantly associated with inferior clinical outcomes, including time to first therapy (TTT) and overall survival (OS). AMC combined with established clinical and molecular prognostic markers significantly improved risk-stratification of CLL patients for TTT. As an elevated AMC at diagnosis is associated with accelerated disease progression, and monocyte-derived cells in the CLL microenvironment promote CLL cell survival and proliferation, these findings suggest that monocytes and monocyte-derived cells are rational therapeutic targets in CLL. Am. J. Hematol. 91:687-691, 2016. © 2016 Wiley Periodicals, Inc.

Authors
Friedman, DR; Sibley, AB; Owzar, K; Chaffee, KG; Slager, S; Kay, NE; Hanson, CA; Ding, W; Shanafelt, TD; Weinberg, JB; Wilcox, RA
MLA Citation
Friedman, DR, Sibley, AB, Owzar, K, Chaffee, KG, Slager, S, Kay, NE, Hanson, CA, Ding, W, Shanafelt, TD, Weinberg, JB, and Wilcox, RA. "Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes: a multi-institutional study." American journal of hematology 91.7 (July 2016): 687-691.
PMID
27037726
Source
epmc
Published In
American Journal of Hematology
Volume
91
Issue
7
Publish Date
2016
Start Page
687
End Page
691
DOI
10.1002/ajh.24376

Abstract A24: The dual PI3K δ/γ inhibitor, RP6530, in combination with ibrutinib or fludarabine, synergistically enhances cytotoxicity in primary CLL cells in vitro.

Authors
Vakkalanka, S; Penmetsa, KV; Chasse, D; Chen, Y; Viswanadha, S; Friedman, DR; Weinberg, JB
MLA Citation
Vakkalanka, S, Penmetsa, KV, Chasse, D, Chen, Y, Viswanadha, S, Friedman, DR, and Weinberg, JB. "Abstract A24: The dual PI3K δ/γ inhibitor, RP6530, in combination with ibrutinib or fludarabine, synergistically enhances cytotoxicity in primary CLL cells in vitro." September 1, 2015.
Source
crossref
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
21
Issue
17 Supplement
Publish Date
2015
Start Page
A24
End Page
A24
DOI
10.1158/1557-3265.HEMMAL14-A24

Perifosine as a potential novel anti-telomerase therapy.

Most tumors circumvent telomere-length imposed replicative limits through expression of telomerase, the reverse transcriptase that maintains telomere length. Substantial evidence that AKT activity is required for telomerase activity exists, indicating that AKT inhibitors may also function as telomerase inhibitors. This possibility has not been investigated in a clinical context despite many clinical trials evaluating AKT inhibitors. We tested if Perifosine, an AKT inhibitor in clinical trials, inhibits telomerase activity and telomere maintenance in tissue culture and orthotopic xenograft models as well as in purified CLL samples from a phase II Perifosine clinical trial. We demonstrate that Perifosine inhibits telomerase activity and induces telomere shortening in a wide variety of cell lines in vitro, though there is substantial heterogeneity in long-term responses to Perifosine between cell lines. Perifosine did reduce primary breast cancer orthotopic xenograft tumor size, but did not impact metastatic burden in a statistically significant manner. However, Perifosine reduced telomerase activity in four of six CLL patients evaluated. Two of the patients were treated for four to six months and shortening of the shortest telomeres occurred in both patients' cells. These results indicate that it may be possible to repurpose Perifosine or other AKT pathway inhibitors as a novel approach to targeting telomerase.

Authors
Holohan, B; Hagiopian, MM; Lai, T-P; Huang, E; Friedman, DR; Wright, WE; Shay, JW
MLA Citation
Holohan, B, Hagiopian, MM, Lai, T-P, Huang, E, Friedman, DR, Wright, WE, and Shay, JW. "Perifosine as a potential novel anti-telomerase therapy." Oncotarget 6.26 (September 2015): 21816-21826.
PMID
26307677
Source
epmc
Published In
Oncotarget
Volume
6
Issue
26
Publish Date
2015
Start Page
21816
End Page
21826

Pan-caspase peptide inhibitor to induce primary chronic lymphocytic leukemia (CLL) cell death through a non-apoptotic and non-necroptotic mechanism

Authors
Friedman, DR; Stewart, T; Guadalupe, E; Brander, DM; Pisetsky, DS; Weinberg, JB
MLA Citation
Friedman, DR, Stewart, T, Guadalupe, E, Brander, DM, Pisetsky, DS, and Weinberg, JB. "Pan-caspase peptide inhibitor to induce primary chronic lymphocytic leukemia (CLL) cell death through a non-apoptotic and non-necroptotic mechanism." May 20, 2015.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
33
Issue
15
Publish Date
2015

Utilization of the Eμ-Myc mouse to model heterogeneity of therapeutic response.

Human aggressive B-cell non-Hodgkin lymphomas (NHL) encompass the continuum between Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL), and display considerable clinical and biologic heterogeneity, most notably related to therapy response. We previously showed that lymphomas arising in the Eμ-Myc transgenic mouse are heterogeneous, mirroring genomic differences between Burkitt lymphoma and DLBCL. Given clinical heterogeneity in NHL and the need to develop strategies to match therapeutics with discrete forms of disease, we investigated the extent to which genomic variation in the Eμ-Myc model predicts response to therapy. We used genomic analyses to classify Eμ-Myc lymphomas, link Eμ-Myc lymphomas with NHL subtypes, and identify lymphomas with predicted resistance to conventional and NF-κB-targeted therapies. Experimental evaluation of these predictions links genomic profiles with distinct outcomes to conventional and targeted therapies in the Eμ-Myc model, and establishes a framework to test novel targeted therapies or combination therapies in specific genomically defined lymphoma subgroups. In turn, this will rationally inform the design of new treatment options for aggressive human NHL.

Authors
Rempel, RE; Jiang, X; Fullerton, P; Tan, TZ; Ye, J; Lau, JA; Mori, S; Chi, J-T; Nevins, JR; Friedman, DR
MLA Citation
Rempel, RE, Jiang, X, Fullerton, P, Tan, TZ, Ye, J, Lau, JA, Mori, S, Chi, J-T, Nevins, JR, and Friedman, DR. "Utilization of the Eμ-Myc mouse to model heterogeneity of therapeutic response." Molecular cancer therapeutics 13.12 (December 2014): 3219-3229.
PMID
25349303
Source
epmc
Published In
Molecular cancer therapeutics
Volume
13
Issue
12
Publish Date
2014
Start Page
3219
End Page
3229
DOI
10.1158/1535-7163.mct-13-0044

Abstract 4518: The PI3K-δ inhibitor TGR-1202 induces cytotoxicity and inhibits phosphorylation of AKT in 17p deleted and non-17p deleted CLL cells in vitro

Authors
Friedman, DR; Simms, T; Allgood, SD; Brander, DM; Sportelli, P; Miskin, HP; Vakkalanka, S; Viswanadha, S; Weinberg, JB; Lanasa, MC
MLA Citation
Friedman, DR, Simms, T, Allgood, SD, Brander, DM, Sportelli, P, Miskin, HP, Vakkalanka, S, Viswanadha, S, Weinberg, JB, and Lanasa, MC. "Abstract 4518: The PI3K-δ inhibitor TGR-1202 induces cytotoxicity and inhibits phosphorylation of AKT in 17p deleted and non-17p deleted CLL cells in vitro." October 1, 2014.
Source
crossref
Published In
Cancer Research
Volume
74
Issue
19 Supplement
Publish Date
2014
Start Page
4518
End Page
4518
DOI
10.1158/1538-7445.AM2014-4518

Perifosine treatment in chronic lymphocytic leukemia: results of a phase II clinical trial and in vitro studies.

Abstract Because of the importance of the phosphoinositide 3-kinase (PI3K)/AKT pathway in chronic lymphocytic leukemia (CLL), we evaluated in vitro cytotoxicity induced by perifosine, an AKT inhibitor, in CLL lymphocytes and found that the mean 50% effective dose (ED50) was 313 nM. We then performed a phase II trial of perifosine in patients with relapsed/refractory CLL to assess response, outcomes, toxicity and ex vivo correlative measures. After 3 months of treatment, six of eight patients showed stable disease, one achieved a partial response and one had progressive disease. Median event-free survival and overall survival in all patients treated were 3.9 and 9.7 months. Adverse events included hematologic, infectious/fever, pain, gastrointestinal and constitutional toxicities. Unexpectedly, AKT phosphorylation in CLL lymphocytes from treated patients was not correlated with response. Additionally, perifosine did not inhibit AKT phosphorylation in cultured CLL lymphocytes. Perifosine is cytotoxic to CLL cells in vitro, and largely induces stabilized disease in vivo, with an AKT-independent mechanism.

Authors
Friedman, DR; Lanasa, MC; Davis, PH; Allgood, SD; Matta, KM; Brander, DM; Chen, Y; Davis, ED; Volkheimer, AD; Moore, JO; Gockerman, JP; Sportelli, P; Weinberg, JB
MLA Citation
Friedman, DR, Lanasa, MC, Davis, PH, Allgood, SD, Matta, KM, Brander, DM, Chen, Y, Davis, ED, Volkheimer, AD, Moore, JO, Gockerman, JP, Sportelli, P, and Weinberg, JB. "Perifosine treatment in chronic lymphocytic leukemia: results of a phase II clinical trial and in vitro studies." Leuk Lymphoma 55.5 (May 2014): 1067-1075.
PMID
23863122
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
55
Issue
5
Publish Date
2014
Start Page
1067
End Page
1075
DOI
10.3109/10428194.2013.824080

CD38 variation as a prognostic factor in chronic lymphocytic leukemia.

Authors
Nipp, RD; Volkheimer, AD; Davis, ED; Chen, Y; Weinberg, JB; Friedman, DR
MLA Citation
Nipp, RD, Volkheimer, AD, Davis, ED, Chen, Y, Weinberg, JB, and Friedman, DR. "CD38 variation as a prognostic factor in chronic lymphocytic leukemia." Leuk Lymphoma 55.1 (January 2014): 191-194. (Letter)
PMID
23510236
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
55
Issue
1
Publish Date
2014
Start Page
191
End Page
194
DOI
10.3109/10428194.2013.786070

"Primum non nocere": the addition of granulocyte-macrophage colony stimulating factor to alemtuzumab in chronic lymphocytic leukemia.

Authors
Friedman, DR
MLA Citation
Friedman, DR. ""Primum non nocere": the addition of granulocyte-macrophage colony stimulating factor to alemtuzumab in chronic lymphocytic leukemia." Leuk Lymphoma 54.3 (March 2013): 441-442.
PMID
22950412
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
54
Issue
3
Publish Date
2013
Start Page
441
End Page
442
DOI
10.3109/10428194.2012.727420

Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function.

Chronic lymphocytic leukemia (CLL) can be immunosuppressive in humans and mice, and CLL cells share multiple phenotypic markers with regulatory B cells that are competent to produce interleukin (IL)-10 (B10 cells). To identify functional links between CLL cells and regulatory B10 cells, the phenotypes and abilities of leukemia cells from 93 patients with overt CLL to express IL-10 were assessed. CD5(+) CLL cells purified from 90% of the patients were IL-10-competent and secreted IL-10 following appropriate ex vivo stimulation. Serum IL-10 levels were also significantly elevated in CLL patients. IL-10-competent cell frequencies were higher among CLLs with IgV(H) mutations, and correlated positively with TCL1 expression. In the TCL1-transgenic (TCL1-Tg) mouse model of CLL, IL-10-competent B cells with the cell surface phenotype of B10 cells expanded significantly with age, preceding the development of overt, CLL-like leukemia. Malignant CLL cells in TCL1-Tg mice also shared immunoregulatory functions with mouse and human B10 cells. Serum IL-10 levels varied in TCL1-Tg mice, but in vivo low-dose lipopolysaccharide treatment induced IL-10 expression in CLL cells and high levels of serum IL-10. Thus, malignant IL-10-competent CLL cells exhibit regulatory functions comparable to normal B10 cells that may contribute to the immunosuppression observed in patients and TCL1-Tg mice.

Authors
DiLillo, DJ; Weinberg, JB; Yoshizaki, A; Horikawa, M; Bryant, JM; Iwata, Y; Matsushita, T; Matta, KM; Chen, Y; Venturi, GM; Russo, G; Gockerman, JP; Moore, JO; Diehl, LF; Volkheimer, AD; Friedman, DR; Lanasa, MC; Hall, RP; Tedder, TF
MLA Citation
DiLillo, DJ, Weinberg, JB, Yoshizaki, A, Horikawa, M, Bryant, JM, Iwata, Y, Matsushita, T, Matta, KM, Chen, Y, Venturi, GM, Russo, G, Gockerman, JP, Moore, JO, Diehl, LF, Volkheimer, AD, Friedman, DR, Lanasa, MC, Hall, RP, and Tedder, TF. "Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function." Leukemia 27.1 (January 2013): 170-182.
PMID
22713648
Source
pubmed
Published In
Leukemia
Volume
27
Issue
1
Publish Date
2013
Start Page
170
End Page
182
DOI
10.1038/leu.2012.165

Clinical and biological relevance of genomic heterogeneity in chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is typically regarded as an indolent B-cell malignancy. However, there is wide variability with regards to need for therapy, time to progressive disease, and treatment response. This clinical variability is due, in part, to biological heterogeneity between individual patients' leukemias. While much has been learned about this biological variation using genomic approaches, it is unclear whether such efforts have sufficiently evaluated biological and clinical heterogeneity in CLL. METHODS: To study the extent of genomic variability in CLL and the biological and clinical attributes of genomic classification in CLL, we evaluated 893 unique CLL samples from fifteen publicly available gene expression profiling datasets. We used unsupervised approaches to divide the data into subgroups, evaluated the biological pathways and genetic aberrations that were associated with the subgroups, and compared prognostic and clinical outcome data between the subgroups. RESULTS: Using an unsupervised approach, we determined that approximately 600 CLL samples are needed to define the spectrum of diversity in CLL genomic expression. We identified seven genomically-defined CLL subgroups that have distinct biological properties, are associated with specific chromosomal deletions and amplifications, and have marked differences in molecular prognostic markers and clinical outcomes. CONCLUSIONS: Our results indicate that investigations focusing on small numbers of patient samples likely provide a biased outlook on CLL biology. These findings may have important implications in identifying patients who should be treated with specific targeted therapies, which could have efficacy against CLL cells that rely on specific biological pathways.

Authors
Friedman, DR; Lucas, JE; Weinberg, JB
MLA Citation
Friedman, DR, Lucas, JE, and Weinberg, JB. "Clinical and biological relevance of genomic heterogeneity in chronic lymphocytic leukemia." PLoS One 8.2 (2013): e57356-.
PMID
23468975
Source
pubmed
Published In
PloS one
Volume
8
Issue
2
Publish Date
2013
Start Page
e57356
DOI
10.1371/journal.pone.0057356

Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function

Chronic lymphocytic leukemia (CLL) can be immunosuppressive in humans and mice, and CLL cells share multiple phenotypic markers with regulatory B cells that are competent to produce interleukin (IL)-10 (B10 cells). To identify functional links between CLL cells and regulatory B10 cells, the phenotypes and abilities of leukemia cells from 93 patients with overt CLL to express IL-10 were assessed. CD5 + CLL cells purified from 90% of the patients were IL-10-competent and secreted IL-10 following appropriate ex vivo stimulation. Serum IL-10 levels were also significantly elevated in CLL patients. IL-10-competent cell frequencies were higher among CLLs with IgV H mutations, and correlated positively with TCL1 expression. In the TCL1-transgenic (TCL1-Tg) mouse model of CLL, IL-10-competent B cells with the cell surface phenotype of B10 cells expanded significantly with age, preceding the development of overt, CLL-like leukemia. Malignant CLL cells in TCL1-Tg mice also shared immunoregulatory functions with mouse and human B10 cells. Serum IL-10 levels varied in TCL1-Tg mice, but in vivo low-dose lipopolysaccharide treatment induced IL-10 expression in CLL cells and high levels of serum IL-10. Thus, malignant IL-10-competent CLL cells exhibit regulatory functions comparable to normal B10 cells that may contribute to the immunosuppression observed in patients and TCL1-Tg mice. © 2013 Macmillan Publishers Limited All rights reserved.

Authors
Dilillo, DJ; Weinberg, JB; Yoshizaki, A; Horikawa, M; Bryant, JM; Iwata, Y; Matsushita, T; Matta, KM; Chen, Y; Venturi, GM; Russo, G; Gockerman, JP; Moore, JO; Diehl, LF; Volkheimer, AD; Friedman, DR; Lanasa, MC; Hall, RP; Tedder, TF
MLA Citation
Dilillo, DJ, Weinberg, JB, Yoshizaki, A, Horikawa, M, Bryant, JM, Iwata, Y, Matsushita, T, Matta, KM, Chen, Y, Venturi, GM, Russo, G, Gockerman, JP, Moore, JO, Diehl, LF, Volkheimer, AD, Friedman, DR, Lanasa, MC, Hall, RP, and Tedder, TF. "Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function." Leukemia 27.1 (2013): 170-182.
Source
scival
Published In
Leukemia
Volume
27
Issue
1
Publish Date
2013
Start Page
170
End Page
182
DOI
10.1038/leu.2012.165

CD38 Variation in Chronic Lymphocytic Leukemia

Authors
Nipp, RD; Weinberg, JB; Volkheimer, AD; Davis, ED; Chen, Y; Friedman, DR
MLA Citation
Nipp, RD, Weinberg, JB, Volkheimer, AD, Davis, ED, Chen, Y, and Friedman, DR. "CD38 Variation in Chronic Lymphocytic Leukemia." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

Modeling Variation in the Human Lymphoma Microenvironment with the E mu-Myc Mouse Model

Authors
Friedman, DR; Rempel, RE; Jiang, X; Nevins, JR
MLA Citation
Friedman, DR, Rempel, RE, Jiang, X, and Nevins, JR. "Modeling Variation in the Human Lymphoma Microenvironment with the E mu-Myc Mouse Model." November 16, 2012.
Source
wos-lite
Published In
Blood
Volume
120
Issue
21
Publish Date
2012

Phase II study of cenersen, an antisense inhibitor of p53, in combination with fludarabine, cyclophosphamide and rituximab for high-risk chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) with deletion or mutation of TP53 have exceedingly poor clinical outcomes. Cenersen, an oligonucleotide targeting TP53, has been shown to abrogate the activity of TP53 gain-of-function mutants and to increase sensitivity of lymphoma cells to cytotoxic chemotherapy in vitro. We combined cenersen with fludarabine, cyclophosphamide and rituximab (FCR) as treatment for patients with high-risk CLL. The purpose of this phase II study was to determine the overall response rate, response duration and toxicity of cenersen administered in combination with FCR. Twenty patients with relapsed or high-risk CLL were evaluated. Nineteen patients were previously treated. The complete response rate was 18%; the overall response rate was 53%. Median progression-free and overall survival was 5.3 and 10.6 months, respectively. The most common serious adverse events were neutropenia and thrombocytopenia. In this single arm phase II study, cenersen combined with FCR yielded clinical responses with acceptable toxicity in patients with high-risk CLL.

Authors
Lanasa, MC; Davis, PH; Datto, M; Li, Z; Gockerman, JP; Moore, JO; DeCastro, CM; Friedman, DR; Diehl, LF; Rehder, C; Cook, H; Daugherty, FJ; Matta, KMB; Weinberg, JB; Rizzieri, D
MLA Citation
Lanasa, MC, Davis, PH, Datto, M, Li, Z, Gockerman, JP, Moore, JO, DeCastro, CM, Friedman, DR, Diehl, LF, Rehder, C, Cook, H, Daugherty, FJ, Matta, KMB, Weinberg, JB, and Rizzieri, D. "Phase II study of cenersen, an antisense inhibitor of p53, in combination with fludarabine, cyclophosphamide and rituximab for high-risk chronic lymphocytic leukemia." Leuk Lymphoma 53.2 (February 2012): 218-224.
PMID
21827374
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
53
Issue
2
Publish Date
2012
Start Page
218
End Page
224
DOI
10.3109/10428194.2011.610012

Chronic Lymphocytic Leukemia Shares a Common Cellular Origin with Regulatory B10 Cells

Authors
Weinberg, JB; DiLillo, DJ; Iwata, Y; Matushita, T; Matta, KM; Venturi, GM; Russo, G; Chen, Y; Gockerman, JP; Moore, JO; Diehl, LF; Volkheimer, AD; Friedman, DR; Lanasa, MC; Hall, RP; Tedder, TJ
MLA Citation
Weinberg, JB, DiLillo, DJ, Iwata, Y, Matushita, T, Matta, KM, Venturi, GM, Russo, G, Chen, Y, Gockerman, JP, Moore, JO, Diehl, LF, Volkheimer, AD, Friedman, DR, Lanasa, MC, Hall, RP, and Tedder, TJ. "Chronic Lymphocytic Leukemia Shares a Common Cellular Origin with Regulatory B10 Cells." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
132
End Page
133

Genomic Heterogeneity in B-Cell Malignancies

Authors
Friedman, DR; Nevins, JR
MLA Citation
Friedman, DR, and Nevins, JR. "Genomic Heterogeneity in B-Cell Malignancies." November 18, 2011.
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
1480
End Page
1480

SET oncoprotein overexpression in B-cell chronic lymphocytic leukemia and non-Hodgkin lymphoma: a predictor of aggressive disease and a new treatment target.

B-cell chronic lymphocytic leukemia (CLL), an incurable leukemia, is characterized by defective apoptosis. We found that the SET oncoprotein, a potent inhibitor of the protein phosphatase 2A (PP2A) tumor suppressor, is overexpressed in primary CLL cells and B-cell non-Hodgkin lymphoma (NHL) cell line cells. In CLL, increased levels of SET correlated significantly with disease severity (shorter time to treatment and overall survival). We developed SET antagonist peptides that bound SET, increased cellular PP2A activity, decreased Mcl-1 expression, and displayed selective cytotoxicity for CLL and NHL cells in vitro. In addition, shRNA for SET was cytotoxic for NHL cells in vitro. The SET antagonist peptide COG449 inhibited growth of NHL tumor xenografts in mice. These data demonstrate that SET is a new treatment target in B-cell malignancies and that SET antagonists represent novel agents for treatment of CLL and NHL.

Authors
Christensen, DJ; Chen, Y; Oddo, J; Matta, KM; Neil, J; Davis, ED; Volkheimer, AD; Lanasa, MC; Friedman, DR; Goodman, BK; Gockerman, JP; Diehl, LF; de Castro, CM; Moore, JO; Vitek, MP; Weinberg, JB
MLA Citation
Christensen, DJ, Chen, Y, Oddo, J, Matta, KM, Neil, J, Davis, ED, Volkheimer, AD, Lanasa, MC, Friedman, DR, Goodman, BK, Gockerman, JP, Diehl, LF, de Castro, CM, Moore, JO, Vitek, MP, and Weinberg, JB. "SET oncoprotein overexpression in B-cell chronic lymphocytic leukemia and non-Hodgkin lymphoma: a predictor of aggressive disease and a new treatment target." Blood 118.15 (October 13, 2011): 4150-4158.
PMID
21844565
Source
pubmed
Published In
Blood
Volume
118
Issue
15
Publish Date
2011
Start Page
4150
End Page
4158
DOI
10.1182/blood-2011-04-351072

Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs.

A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcriptome of normal and malignant B cells through deep sequencing of 31 normal and malignant human B-cell samples that comprise the spectrum of B-cell differentiation and common malignant phenotypes. We identified the expression of 333 known miRNAs, which is more than twice the number previously recognized in any tissue type. We further identified the expression of 286 candidate novel miRNAs in normal and malignant B cells. These miRNAs were validated at a high rate (92%) using quantitative polymerase chain reaction, and we demonstrated their application in the distinction of clinically relevant subgroups of lymphoma. We further demonstrated that a novel miRNA cluster, previously annotated as a hypothetical gene LOC100130622, contains 6 novel miRNAs that regulate the transforming growth factor-β pathway. Thus, our work suggests that more than a third of the miRNAs present in most cellular types are currently unknown and that these miRNAs may regulate important cellular functions.

Authors
Jima, DD; Zhang, J; Jacobs, C; Richards, KL; Dunphy, CH; Choi, WWL; Au, WY; Srivastava, G; Czader, MB; Rizzieri, DA; Lagoo, AS; Lugar, PL; Mann, KP; Flowers, CR; Bernal-Mizrachi, L; Naresh, KN; Evens, AM; Gordon, LI; Luftig, M; Friedman, DR; Weinberg, JB; Thompson, MA; Gill, JI; Liu, Q; How, T; Grubor, V; Gao, Y; Patel, A; Wu, H; Zhu, J; Blobe, GC; Lipsky, PE; Chadburn, A; Dave, SS; Hematologic Malignancies Research Consortium,
MLA Citation
Jima, DD, Zhang, J, Jacobs, C, Richards, KL, Dunphy, CH, Choi, WWL, Au, WY, Srivastava, G, Czader, MB, Rizzieri, DA, Lagoo, AS, Lugar, PL, Mann, KP, Flowers, CR, Bernal-Mizrachi, L, Naresh, KN, Evens, AM, Gordon, LI, Luftig, M, Friedman, DR, Weinberg, JB, Thompson, MA, Gill, JI, Liu, Q, How, T, Grubor, V, Gao, Y, Patel, A, Wu, H, Zhu, J, Blobe, GC, Lipsky, PE, Chadburn, A, Dave, SS, and Hematologic Malignancies Research Consortium, . "Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs." Blood 116.23 (December 2, 2010): e118-e127.
PMID
20733160
Source
pubmed
Published In
Blood
Volume
116
Issue
23
Publish Date
2010
Start Page
e118
End Page
e127
DOI
10.1182/blood-2010-05-285403

Statin use and need for therapy in chronic lymphocytic leukemia.

Authors
Friedman, DR; Magura, LA; Warren, HAC; Harrison, JD; Diehl, LF; Weinberg, JB
MLA Citation
Friedman, DR, Magura, LA, Warren, HAC, Harrison, JD, Diehl, LF, and Weinberg, JB. "Statin use and need for therapy in chronic lymphocytic leukemia." Leukemia & lymphoma 51.12 (December 2010): 2295-2298. (Letter)
PMID
20929315
Source
epmc
Published In
Leukemia & Lymphoma (Informa)
Volume
51
Issue
12
Publish Date
2010
Start Page
2295
End Page
2298
DOI
10.3109/10428194.2010.520050

Pre-Clinical and Interim Results of a Phase II Trial of Perifosine In Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Authors
Friedman, DR; Davis, PH; Lanasa, MC; Moore, JO; Gockerman, JP; Nelson, T; Bond, KM; Jiang, N; Davis, ED; Allgood, SD; Chen, Y; Sportelli, P; Weinberg, JB
MLA Citation
Friedman, DR, Davis, PH, Lanasa, MC, Moore, JO, Gockerman, JP, Nelson, T, Bond, KM, Jiang, N, Davis, ED, Allgood, SD, Chen, Y, Sportelli, P, and Weinberg, JB. "Pre-Clinical and Interim Results of a Phase II Trial of Perifosine In Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)." November 19, 2010.
Source
wos-lite
Published In
Blood
Volume
116
Issue
21
Publish Date
2010
Start Page
768
End Page
769

LMP-420: a novel purine nucleoside analog with potent cytotoxic effects for CLL cells and minimal toxicity for normal hematopoietic cells.

B-cell chronic lymphocytic leukemia (CLL) is characterized by slow accumulation of malignant cells, which are supported in the microenvironment by cell-cell interactions and soluble cytokines such as tumor necrosis factor (TNF). We evaluated the effect of the small molecule TNF inhibitor LMP-420 on primary CLL cells. The mean concentration of LMP-420 required to induce 50% cytotoxicity (ED50) at 72 h was 245 n. LMP-420-induced time- and dose-dependent apoptosis, as shown by annexin V staining, caspase activation and DNA fragmentation. These changes were associated with decreased expression of anti-apoptotic proteins Mcl-1, Bcl-xL and Bcl-2. CLL cells from patients with poor prognostic indicators showed LMP-420 sensitivity equal to that for cells from patients with favorable characteristics. In addition, LMP-420 potentiated the cytotoxic effect of fludarabine and inhibited in vitro proliferation of stimulated CLL cells. Gene expression profiling indicated that the mechanism of action of LMP-420 may involve suppression of nuclear factor-kappaB and immune response pathways in CLL cells. LMP-420 had minimal effects on normal peripheral blood mononuclear cell, B- and T-cell function, and hematopoietic colony formation. Our data suggest that LMP-420 may be a useful treatment for CLL with negligible hematologic toxicities.

Authors
Mowery, YM; Weinberg, JB; Kennedy, MN; Bond, KM; Moore, JO; Lanasa, MC; Gockerman, JP; Diehl, LF; Pizzo, SV; Cianciolo, GJ; Friedman, DR
MLA Citation
Mowery, YM, Weinberg, JB, Kennedy, MN, Bond, KM, Moore, JO, Lanasa, MC, Gockerman, JP, Diehl, LF, Pizzo, SV, Cianciolo, GJ, and Friedman, DR. "LMP-420: a novel purine nucleoside analog with potent cytotoxic effects for CLL cells and minimal toxicity for normal hematopoietic cells." Leukemia 24.9 (September 2010): 1580-1587.
PMID
20613784
Source
epmc
Published In
Leukemia
Volume
24
Issue
9
Publish Date
2010
Start Page
1580
End Page
1587
DOI
10.1038/leu.2010.150

Informational needs assessment of non-Hodgkin lymphoma survivors and their physicians.

Authors
Friedman, DR; Coan, AD; Smith, SK; Herndon, JE; Abernethy, AP
MLA Citation
Friedman, DR, Coan, AD, Smith, SK, Herndon, JE, and Abernethy, AP. "Informational needs assessment of non-Hodgkin lymphoma survivors and their physicians." Am J Hematol 85.7 (July 2010): 528-532. (Letter)
PMID
20575038
Source
pubmed
Published In
American Journal of Hematology
Volume
85
Issue
7
Publish Date
2010
Start Page
528
End Page
532
DOI
10.1002/ajh.21725

The Anti-Inflammatory Investigational Agent LMP-420 Demonstrates in Vitro Cytotoxic Activity against Chronic Lymphocytic Leukemia Cells

Authors
Friedman, DR; Mowery, Y; Kennedy, M; Bond, KM; Weinberg, JB; Cianciolo, GJ
MLA Citation
Friedman, DR, Mowery, Y, Kennedy, M, Bond, KM, Weinberg, JB, and Cianciolo, GJ. "The Anti-Inflammatory Investigational Agent LMP-420 Demonstrates in Vitro Cytotoxic Activity against Chronic Lymphocytic Leukemia Cells." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
931
End Page
931

Influence of Statin Therapy On the Clinical Course of Chronic Lymphocytic Leukemia

Authors
Friedman, DR; Harrison, JD; Magura, LA; Warren, HA; Diehl, LF; Weinberg, JB
MLA Citation
Friedman, DR, Harrison, JD, Magura, LA, Warren, HA, Diehl, LF, and Weinberg, JB. "Influence of Statin Therapy On the Clinical Course of Chronic Lymphocytic Leukemia." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
926
End Page
926

A Comprehensive Identification of the Microrna Transcriptome and Its Application in B Cell Malignancies

Authors
Jacobs, CL; Jima, DD; Zhang, J; Dunphy, C; Richards, KL; Choi, WWL; Srivastava, G; Evens, AM; Gordon, LI; Czader, M; Rizzieri, DA; Lagoo, AS; Mann, KP; Flowers, CR; Naresh, K; Luftig, M; Friedman, DR; Weinberg, JB; Thompson, MA; Gill, J; Kahl, BS; Chadburn, A; Dave, S
MLA Citation
Jacobs, CL, Jima, DD, Zhang, J, Dunphy, C, Richards, KL, Choi, WWL, Srivastava, G, Evens, AM, Gordon, LI, Czader, M, Rizzieri, DA, Lagoo, AS, Mann, KP, Flowers, CR, Naresh, K, Luftig, M, Friedman, DR, Weinberg, JB, Thompson, MA, Gill, J, Kahl, BS, Chadburn, A, and Dave, S. "A Comprehensive Identification of the Microrna Transcriptome and Its Application in B Cell Malignancies." November 20, 2009.
Source
wos-lite
Published In
Blood
Volume
114
Issue
22
Publish Date
2009
Start Page
948
End Page
949

A genomic approach to improve prognosis and predict therapeutic response in chronic lymphocytic leukemia.

PURPOSE: Chronic lymphocytic leukemia (CLL) is a B-cell malignancy characterized by a variable clinical course. Several parameters have prognostic capabilities but are associated with altered response to therapy in only a small subset of patients. EXPERIMENTAL DESIGN: We used gene expression profiling methods to generate predictors of therapy response and prognosis. Genomic signatures that reflect progressive disease and responses to chemotherapy or chemoimmunotherapy were created using cancer cell lines and patient leukemia cell samples. We validated and applied these three signatures to independent clinical data from four cohorts, representing a total of 301 CLL patients. RESULTS: A genomic signature of prognosis created from patient leukemic cell gene expression data coupled with clinical parameters significantly differentiated patients with stable disease from those with progressive disease in the training data set. The progression signature was validated in two independent data sets, showing a capacity to accurately identify patients at risk for progressive disease. In addition, genomic signatures that predict response to chlorambucil or pentostatin, cyclophosphamide, and rituximab were generated and could accurately distinguish responding and nonresponding CLL patients. CONCLUSIONS: Thus, microarray analysis of CLL lymphocytes can be used to refine prognosis and predict response to different therapies. These results have implications for standard and investigational therapeutics in CLL patients.

Authors
Friedman, DR; Weinberg, JB; Barry, WT; Goodman, BK; Volkheimer, AD; Bond, KM; Chen, Y; Jiang, N; Moore, JO; Gockerman, JP; Diehl, LF; Decastro, CM; Potti, A; Nevins, JR
MLA Citation
Friedman, DR, Weinberg, JB, Barry, WT, Goodman, BK, Volkheimer, AD, Bond, KM, Chen, Y, Jiang, N, Moore, JO, Gockerman, JP, Diehl, LF, Decastro, CM, Potti, A, and Nevins, JR. "A genomic approach to improve prognosis and predict therapeutic response in chronic lymphocytic leukemia." Clin Cancer Res 15.22 (November 15, 2009): 6947-6955.
PMID
19861443
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
15
Issue
22
Publish Date
2009
Start Page
6947
End Page
6955
DOI
10.1158/1078-0432.CCR-09-1132

Survivorship care planning needs in diffuse large B-cell lymphoma (DLBCL)

Authors
Friedman, DR; Dupont, AH; Coan, AD; II, HJE; Rowe, KL; Abernethy, AP
MLA Citation
Friedman, DR, Dupont, AH, Coan, AD, II, HJE, Rowe, KL, and Abernethy, AP. "Survivorship care planning needs in diffuse large B-cell lymphoma (DLBCL)." May 20, 2009.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
27
Issue
15
Publish Date
2009

Patterns of microRNA expression characterize stages of human B-cell differentiation.

Mature B-cell differentiation provides an important mechanism for the acquisition of adaptive immunity. Malignancies derived from mature B cells constitute the majority of leukemias and lymphomas. These malignancies often maintain the characteristics of the normal B cells that they are derived from, a feature that is frequently used in their diagnosis. The role of microRNAs in mature B cells is largely unknown. Through concomitant microRNA and mRNA profiling, we demonstrate a potential regulatory role for microRNAs at every stage of the mature B-cell differentiation process. In addition, we have experimentally identified a direct role for the microRNA regulation of key transcription factors in B-cell differentiation: LMO2 and PRDM1 (Blimp1). We also profiled the microRNA of B-cell tumors derived from diffuse large B-cell lymphoma, Burkitt lymphoma, and chronic lymphocytic leukemia. We found that, in contrast to many other malignancies, common B-cell malignancies do not down-regulate microRNA expression. Although these tumors could be distinguished from each other with use of microRNA expression, each tumor type maintained the expression of the lineage-specific microRNAs. Expression of these lineage-specific microRNAs could correctly predict the lineage of B-cell malignancies in more than 95% of the cases. Thus, our data demonstrate that microRNAs may be important in maintaining the mature B-cell phenotype in normal and malignant B cells.

Authors
Zhang, J; Jima, DD; Jacobs, C; Fischer, R; Gottwein, E; Huang, G; Lugar, PL; Lagoo, AS; Rizzieri, DA; Friedman, DR; Weinberg, JB; Lipsky, PE; Dave, SS
MLA Citation
Zhang, J, Jima, DD, Jacobs, C, Fischer, R, Gottwein, E, Huang, G, Lugar, PL, Lagoo, AS, Rizzieri, DA, Friedman, DR, Weinberg, JB, Lipsky, PE, and Dave, SS. "Patterns of microRNA expression characterize stages of human B-cell differentiation." Blood 113.19 (May 7, 2009): 4586-4594.
PMID
19202128
Source
pubmed
Published In
Blood
Volume
113
Issue
19
Publish Date
2009
Start Page
4586
End Page
4594
DOI
10.1182/blood-2008-09-178186

Clinical and molecular predictors of disease severity and survival in chronic lymphocytic leukemia.

Several parameters may predict disease severity and overall survival in chronic lymphocytic leukemia (CLL). The purpose of our study of 190 CLL patients was to compare immunoglobulin heavy chain variable region (IgV(H)) mutation status, cytogenetic abnormalities, and leukemia cell CD38 and Zap-70 to older, traditional parameters. We also wanted to construct a simple, inexpensive prognosis score that would significantly predict TTT and survival in patients at the time of diagnosis and help practicing clinicians. In univariate analyses, patients with higher clinical stage, higher leukocyte count at diagnosis, shorter leukocyte doubling time, elevated serum lactate dehydrogenase (LDH), unmutated immunoglobulin heavy chain variable region (IgV(H)) genes, and higher CD38 had a shorter overall survival and time-to-treatment (TTT). CLL cell Zap-70 expression was higher in patients with unmutated IgV(H), and those with higher Zap-70 tended to have shorter survival. IgV(H)4-34 or IgV(H)1-69 was the most common IgV(H) genes used (16 and 12%, respectively). Of those with IgV(H)1-69, 86% had unmutated IgV(H) and had a significantly shorter TTT. A cytogenetic abnormality was noted in 71% of the patients tested. Patients with 11q22 del and 17p13 del or complex abnormalities were significantly more likely to have unmutated IgV(H). We found that a prognostic score constructed using modified Rai stage, cellular CD38, and serum LDH (parameters easily obtained clinically) significantly predicted TTT and survival in patients at the time of diagnosis and performed as well or better than models using the newer markers.

Authors
Weinberg, JB; Volkheimer, AD; Chen, Y; Beasley, BE; Jiang, N; Lanasa, MC; Friedman, D; Vaccaro, G; Rehder, CW; Decastro, CM; Rizzieri, DA; Diehl, LF; Gockerman, JP; Moore, JO; Goodman, BK; Levesque, MC
MLA Citation
Weinberg, JB, Volkheimer, AD, Chen, Y, Beasley, BE, Jiang, N, Lanasa, MC, Friedman, D, Vaccaro, G, Rehder, CW, Decastro, CM, Rizzieri, DA, Diehl, LF, Gockerman, JP, Moore, JO, Goodman, BK, and Levesque, MC. "Clinical and molecular predictors of disease severity and survival in chronic lymphocytic leukemia." Am J Hematol 82.12 (December 2007): 1063-1070.
PMID
17654680
Source
pubmed
Published In
American Journal of Hematology
Volume
82
Issue
12
Publish Date
2007
Start Page
1063
End Page
1070
DOI
10.1002/ajh.20987

Review of targeted cancer therapies for the palliative care provider Part 1: Small molecules

The incorporation of 'targeted therapies' into standard cancer care has changed how clinicians treat cancer. Small molecule inhibitors, antibodies, and conjugated agents target cancer cells more specifically than traditional chemotherapy. These therapies can be used alone or in combination with chemotherapy in first-line, refractory, or relapsed settings. Although designed to spare normal tissue, these agents do have systemic toxicity. Notably, their toxicity profiles are distinct from those encountered with chemotherapy. These agents have demonstrated efficacy in terms of improved tumour response, survival, symptom control, and/or quality of life. Cancer treatment will continue to change as additional targeted agents are evaluated in clinical trials and are brought into standard medical care. The palliative care clinician is likely to encounter these agents with increasing frequency, making decisions to continue or discontinue therapy, adding targeted agents to improve symptoms, performance status, or quality of life, or advising patients to return to their oncologists for further advice as new agents become available. Presented here, Part I of this review focuses on small molecules. All but one of these agents are oral, and they are all relatively well tolerated. In the future, Part 2 will introduce antibodies and conjugated agents.

Authors
Friedman, DR; Abernethy, AP
MLA Citation
Friedman, DR, and Abernethy, AP. "Review of targeted cancer therapies for the palliative care provider Part 1: Small molecules." Progress in Palliative Care 15.4 (2007): 171-176.
Source
scival
Published In
Progress in Palliative Care
Volume
15
Issue
4
Publish Date
2007
Start Page
171
End Page
176
DOI
10.1179/096992607X177863

Review of targeted cancer therapies for the palliative care provider PART 2: Antibodies and conjugated agents

The incorporation of 'targeted therapies' into standard cancer care has changed how clinicians treat cancer. Small molecule inhibitors, antibodies, and conjugated agents target cancer cells more specifically than traditional chemotherapy. These therapies can be used alone or in combination with chemotherapy in first-line, refractory, or relapsed settings. Although designed to spare normal tissue, these agents do have systemic toxicity. Notably, their toxicity profiles are distinct from those encountered with chemotherapy. These agents have demonstrated efficacy in terms of improved tumour response, survival, symptom control, and/or quality of life. Cancer treatment will continue to change as additional targeted agents are evaluated in clinical trials and are brought into standard medical care. The palliative care clinician is likely to encounter these agents with increasing frequency, making decisions to continue or discontinue therapy, adding targeted agents to improve symptoms, performance status, or quality of life, or advising patients to return to their oncologists for further advice as new agents become available. Presented previously, Part 1 of this review introduced small molecule inhibitors; presented here, Part 2 focuses on antibodies and conjugated agents. The antibodies and conjugated agents are infusional with potentially greater side effects than the small molecules. If used in palliative care, these antibodies and conjugated agents are likely to be administered in conjunction with an oncologist.

Authors
Friedman, DR; Abernethy, AP
MLA Citation
Friedman, DR, and Abernethy, AP. "Review of targeted cancer therapies for the palliative care provider PART 2: Antibodies and conjugated agents." Progress in Palliative Care 15.5 (2007): 225-232.
Source
scival
Published In
Progress in Palliative Care
Volume
15
Issue
5
Publish Date
2007
Start Page
225
End Page
232
DOI
10.1179/096992607X217958

Cocaine-induced pseudovasculitis.

Pseudovasculitis is a disease process that mimics the presentation and possibly the laboratory findings of true vasculitis. However, biopsy specimens do not reveal the typical histopathologic findings expected in vasculitis. One often overlooked cause of pseudovasculitis is cocaine use, which has been described in case reports to cause aggressive nasal destruction and various skin lesions and thus has been confused with Wegener granulomatosis or leukocytoclastic vasculitis. Unfortunately, serologic tests such as antinuclear antibody or antineutrophil cytoplasmic antibody cannot reliably differentiate between these entities. We describe a patient who presented with what was believed to be Wegener granulomatosis affecting the skin and upper airway. However, findings from repeated biopsies did not support this diagnosis, and the only unifying diagnosis was cocaine-induced pseudovasculitis. The ability to recognize and differentiate between true vasculitis and pseudovasculitis is essential for the clinician because treatment options are radically disparate.

Authors
Friedman, DR; Wolfsthal, SD
MLA Citation
Friedman, DR, and Wolfsthal, SD. "Cocaine-induced pseudovasculitis." Mayo Clin Proc 80.5 (May 2005): 671-673.
PMID
15887436
Source
pubmed
Published In
Mayo Clinic Proceedings
Volume
80
Issue
5
Publish Date
2005
Start Page
671
End Page
673
DOI
10.4065/80.5.671

Interleukin-15 augments superoxide production and microbicidal activity of human monocytes against Candida albicans

Interleukin-15 (IL-15) is a newly described cytokine that shares biological activities with IL-2. We report here results demonstrating the ability of IL-15 to enhance superoxide production and antifungal activity of human monocytes. After 18 and 48 h of treatment with IL-15, human elutriated monocytes manifested enhanced superoxide production in response to either phorbol myristate acetate or opsonized Candida albicans blastoconidia. Similar results were obtained when monocytes were treated with IL-2, but to a lesser extent. Combination studies with IL-15 and IL-2 showed no additive or synergistic effects. Following incubation of monocytes with IL-15 for 18 h, there was no significant increase in mRNA transcripts for components of the NADPH oxidase complex, p40-phox, p47-phox, and gp91-phox, suggesting a posttranscriptional modulation of enhanced superoxide production. Antibodies against the γ chain of the IL-2 receptor and, to a lesser extent, against the β chain partially abrogated the IL-15-mediated enhanced superoxide production. Additionally, human monocytes showed enhanced killing activity against C. albicans after 18 h of incubation with IL-15 or IL-2, but this treatment did not enhance the ability of these cells to phagocytose the organism. In addition, the enhanced fungicidal activity seen after 18 h of treatment was no longer detectable after 48 h of cytokine treatment. Culture supernatants from the IL-15-treated monocytes were assayed for the presence of other proinflammatory cytokines. IL-15 treatment did not induce the release of detectable levels of tumor necrosis factor alpha, IL-1β, or IL- 12. Our results indicate that IL-15 upregulates the microbicidal activity of human monocytes against C. albicans.

Authors
Vázquez, N; Walsh, TJ; Friedman, D; Chanock, SJ; Lyman, CA
MLA Citation
Vázquez, N, Walsh, TJ, Friedman, D, Chanock, SJ, and Lyman, CA. "Interleukin-15 augments superoxide production and microbicidal activity of human monocytes against Candida albicans." Infection and Immunity 66.1 (1998): 145-150.
PMID
9423851
Source
scival
Published In
Infection and immunity
Volume
66
Issue
1
Publish Date
1998
Start Page
145
End Page
150
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