Cell Differentiating Agent

2020 ◽  
Author(s):  
Keyword(s):  
Differentiating Agent

scholarly journals CD1d expression in glioblastoma is a promising target for NKT cell-based cancer immunotherapy

2020 ◽  
Author(s):  
Ayaka Hara ◽  
Ryo Koyama-Nasu ◽  
Mariko Takami ◽  
Takahide Toyoda ◽  
Takahiro Aoki ◽  
...  
Keyword(s):  
Tumor Regression ◽  
Inkt Cell ◽  
Glioblastoma Cells ◽  
Inkt Cells ◽  
Nkt Cell ◽  
Promising Target ◽  
Differentiating Agent ◽  
Novel Target ◽  
Orthotopic Xenografts

Abstract Glioblastoma is the most common and aggressive type of brain tumor with high recurrence and fatality rates. Although various therapeutic strategies have been explored, there is currently no effective treatment for glioblastoma. Recently, the number of immunotherapeutic strategies has been tested for malignant brain tumors. Invariant natural killer T (iNKT) cells play an important role in anti-tumor immunity. To address if iNKT cells can target glioblastoma to exert anti-tumor activity, we assessed the expression of CD1d, an antigen-presenting molecule for iNKT cells, on glioblastoma cells. Glioblastoma cells from 10 of 15 patients expressed CD1d, and CD1d-positive glioblastoma cells pulsed with glycolipid ligand induced iNKT cell-mediated cytotoxicity in vitro. Although CD1d expression was low on glioblastoma stem-like cells, retinoic acid, which is the most common differentiating agent, upregulated CD1d expression in these cells and induced iNKT cell-mediated cytotoxicity. Moreover, intracranial administration of human iNKT cells induced tumor regression of CD1d-positive glioblastoma in orthotopic xenografts in NOD/Shi-scid IL-2RγKO (NOG) mice. Thus, CD1d expression represents a novel target for NKT cell-based immunotherapy for glioblastoma patients.

Ras modulates commitment and maturation of 10T½ fibroblasts to adipocytes

1992 ◽  
Vol 70 (10-11) ◽  
pp. 1249-1257 ◽  
Author(s):  
Ying Lu ◽  
Steve Anderson ◽  
Michael J. Corbley ◽  
Yu-Chun Zhou ◽  
Hugh Pross ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Human Cancer ◽  
Low Frequency ◽  
Positive Association ◽  
Mesenchymal Cell ◽  
Negative Regulator ◽  
Ras Gene ◽  
Positive Role ◽  
Adipose Conversion ◽  
Differentiating Agent

The positive association of the ras oncogene with human cancer and the recognition that malignancy may, in part, represent the imbalance between cell proliferation and differentiation have generated intense interest in the potential role of ras in cell differentiation. We investigated this possibility utilizing as a model system the differentiation of the mesenchymal cell line C3H 10T½ (10T½) to adipocytes, and a series of transfectants of 10T½ cells in which the level of the ras gene product (p21ras; Ras) can be effectively up- or down-modulated. In agreement with previous reports, we found that 10T½ cultures, propagated in the resting state for several weeks, spontaneously convert to fat cells at a very low frequency. Downmodulation of endogenous p21ras levels, as a consequence of expression of antisense ras, markedly increased the rapidity and frequency of adipose conversion (6- to 10-fold), which was equivalent in magnitude to that effected by the potent differentiating agent 5-azacytidine. Conversely, overexpression of ras completely inhibited cell differentiation. In addition, adipocytes derived from antisense-ras expressing lines were characterized by a decrease in hormone responsiveness, as well as an apparent deficiency in attaining the terminally differentiated state. These findings suggest that Ras may be a negative regulator of the decision-making step of fibroblast differentiation to adipocytes. In addition, Ras may play an essential positive role in the transduction of hormonal signals necessary for full adipocytic maturation during later progression along the differentiation pathway.Key words: ras protooncogene, cell differentiation, signal transduction, insulin, adipocytes.

Butyrate as a differentiating agent: pharmacokinetics, analogues and current status

1994 ◽  
Vol 78 (1-3) ◽  
pp. 1-5 ◽  
Author(s):  
Harold L. Newmark ◽  
Joanne R. Lupton ◽  
Charles W. Young
Keyword(s):  
Current Status ◽  
Differentiating Agent

Rapid Cyclosporine Tapering and Isotretinoin Usage after Unrelated Donor Hematopoietic Stem Cell Transplantation in Juvenile Myelomonocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5188-5188
Author(s):  
Keon Hee Yoo ◽  
Soo Hyun Lee ◽  
Ki Woong Sung ◽  
Hong Hoe Koo ◽  
Hye Lim Jung
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Juvenile Myelomonocytic Leukemia ◽  
Hematopoietic Stem ◽  
Differentiating Agent ◽  
Myelomonocytic Leukemia ◽  
Disease Free

Abstract Juvenile myelomonocytic leukemia (JMML) is a rare type of childhood leukemias, and allogeneic hematopoietic stem cell transplantation (HSCT) is known to be the only way to cure the disease. Unfortunately, relapse is still the most frequent cause of treatment failure after transplant in JMML. We investigated the feasibility of inducing graft versus leukemia (GVL) effect and the use of a differentiating agent even after unrelated HSCT in children with JMML. Seven consecutive patients with JMML underwent unrelated HSCT at a median age of 17 months. The sources of grafts were bone marrows (n=3) or HLA 1- or 2-antigen mismatched cord bloods (n=4). Only 3 of the 7 patients were in complete remission before transplantation. Intravenous busulfan, cyclophosphamide, and etoposide were used as preparative agents except in one who was conditioned with TBI-based regimen. Cyclosporine was used universally for GVHD prophylaxis with additional use of short-term methotrexate in bone marrow transplants and of methyl-prednisolone in cord blood transplants. Cyclosporine was tapered rapidly from around 1 month post-HSCT and isotretinoin (75–100 mg/m2/day) was used in selected patients who have any risk factors of relapse. Cyclosporine blood levels were 247.8±91.1, 146.6±104.2, and 88.8±52.6 ng/mL at 1, 2, and 3 months post-transplant, respectively. There was no grade 3 or 4 acute GVHD and only 2 patients developed grade 2 acute GVHD which was improved without additional treatment. Chronic GVHD was developed in 3 (1 limited, 2 extensive) of the evaluable 5 patents, which was all resolved after combined use of immune suppressive agents. Initial chimeric status analysis at 1 month revealed complete donor chimerism (CC) in 4 patients, mixed chimerism (MC) in 2 and autologous recovery (AR) in one. One of the patients with MC and the one with AR were in disease-free status. One patient whose chimeric status changed from CC to MC eventually relapsed. One patient with initial MC with residual disease turned to CC with complete remission. Another patient with initial MC but with no evidence of disease is on treatment with isotretinoin without relapse for 3 months even with persistent MC. The patient with AR relapsed early after transplant. Five patients are alive relapse-free and disease-free with a median follow-up of 16 months after transplant. The Kaplan-Meier probability of event-free survival was 66.7%. We suggest that GVL induction strategy with concomittant use of a differentiating agent might have a role to suppress leukemic relapse in JMML.

scholarly journals Transient Downregulation of Nanog and Oct4 Induced by DETA/NO Exposure in Mouse Embryonic Stem Cells Leads to Mesodermal/Endodermal Lineage Differentiation

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Sergio Mora-Castilla ◽  
Juan R. Tejedo ◽  
Rafael Tapia-Limonchi ◽  
Irene Díaz ◽  
Ana B. Hitos ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Histone H3 ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Directed Differentiation ◽  
Lineage Differentiation ◽  
Induction Of Differentiation ◽  
Differentiating Agent ◽  
Pluripotency Genes

The function of pluripotency genes in differentiation is a matter of investigation. We report here that Nanog and Oct4 are reexpressed in two mouse embryonic stem cell (mESC) lines following exposure to the differentiating agent DETA/NO. Both cell lines express a battery of both endoderm and mesoderm markers following induction of differentiation with DETA/NO-based protocols. Confocal analysis of cells undergoing directed differentiation shows that the majority of cells expressing Nanog express also endoderm genes such as Gata4 and FoxA2 (75.4% and 96.2%, resp.). Simultaneously, mRNA of mesodermal markers Flk1 and Mef2c are also regulated by the treatment. Acetylated histone H3 occupancy at the promoter of Nanog is involved in the process of reexpression. Furthermore, Nanog binding to the promoter of Brachyury leads to repression of this gene, thus disrupting mesendoderm transition.

Effects of the Differentiating Agent Hexamethylene Bisacetamide on Normal and Myelodysplastic Hematopoietic Progenitors

1990 ◽  
Vol 82 (24) ◽  
pp. 1926-1931 ◽  
Author(s):  
E. K. Rowinsky ◽  
R. C. Donehower ◽  
J. L. Spivak ◽  
P. J. Burke ◽  
C. A. Griffin ◽  
...  
Keyword(s):  
Hematopoietic Progenitors ◽  
Hexamethylene Bisacetamide ◽  
Differentiating Agent

scholarly journals Proliferative pathways in CD1- CD3+ CD4+ CD8+ T-prolymphocytic leukemic cells: analysis with monoclonal antibodies and cytokines

Blood ◽  
1989 ◽  
Vol 74 (5) ◽  
pp. 1651-1657 ◽  
Author(s):  
MC Turco ◽  
M De Felice ◽  
F Alfinito ◽  
A Lamberti ◽  
F Costanzo ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Interleukin 1 ◽  
Interleukin 2 ◽  
Hla Class I ◽  
Leukemic Cells ◽  
Ifn Gamma ◽  
Prolymphocytic Leukemia ◽  
Activated State ◽  
Normal Functional ◽  
Differentiating Agent

Abstract The antigenic profile and the proliferative pathways in leukemic cells from the patient TRT with T-prolymphocytic leukemia (T-PLL) were analyzed using monoclonal antibodies (MoAbs) and cytokines. T-PLL cells expressed the phenotype CD1- CD3+ CD4+ CD8+. Incubation with the differentiating agent phorbol-12-myristate-13-acetate markedly increased the percentage of cells with the CD4- CD8+ phenotype, suggesting that leukemic cells were already committed towards a differentiated element with the CD4- CD8+ phenotype. T-PLL cells were induced to proliferate by anti-CD2 MoAb 9–1 + 9.6 and by anti-CD3 MoAb OKT3. The two pathways exhibited normal functional interactions and were susceptible to modulation by anti-HLA class I MoAbs. These results indicate that regulation of cell proliferation was preserved to a significant extent in the T-PLL cells analyzed. At variance with normal resting T cells that require previous activation to proliferate when incubated with interleukin-1 (IL-1) or interleukin-2 (IL-2), T-PLL cells proliferated vigorously when incubated with either interleukin. Furthermore, T-PLL cells proliferated when incubated with immune interferon (IFN-gamma). The latter finding parallels the enhancement by IFN-gamma of the proliferative response of lectin-activated murine T lymphocytes. These results suggest that T-PLL cells, which express a high constitutive level of c-myc mRNA, may be in an activated state. The antigenic phenotype and the characteristics of the proliferative pathways of T-PLL cells from the patient TRT are compatible with the possibility that they may be derived from an intermediate thymocyte.

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