摘要:

AbstractHexamethylene bisacetamide (HMBA), a highly polar compound, induces murine erythroleukemia (MEL) cells to express the erythroid phenotype, including cessation of proliferation. Inducer‐mediated differentiation of MEL (DS19) cells is a multistep process characterized by a latent period during which a number of changes occur including alterations in ion flux, an increase in membrane‐bound protein kinase C (PKC) activity, the appearance of Ca2+and phospholipid‐independent PKC activity in the cytosol, and modulation in expression of a number of genes such as c‐myc,c‐myb,c‐fos and the p53 genes.HMBA‐mediated commitment to terminal differentiation is first detected at about 12 hours and increases in a stochastic fashion until over 95% of the population is recruited to terminal differentiation by 48 to 60 hours. Commitment is associated with persistent suppression of c‐myb gene expression.By 36 to 48 hours, transcription of the globin genes has increased 10 to 30 fold, whereas transcription from rRNA genes is suppressed. The steroid, dexamethasone, or the tumor promoter, phorbol‐12‐myristate‐13‐acetate (TPA), suppress HMBA‐induced MEL cell terminal differentiation. These agents appear to act at a late step during the latent period. MEL cell lines derived from DS19 by selection for resistance to vincristine are: 1) induced to commit without a detectable latent period, 2) markedly more sensitive to HMBA, and 3) resistant to dexamethasone or TPA inhibition of HMBA‐induced commitment. The data suggests that vincristine‐resistant MEL cells express a factor which circumvents essential HMBA‐mediated early events. In vitro studies with HMBA provide a basis for the application of HMBA to clinical therapy of human cancers. Clinical trial

ISSN:0737-1454    

DOI:10.1002/stem.5530060402

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThe modulation of growth of normal and leukemic myeloid progenitor cells in soft agar cultures by recombinant human tumor necrosis factor‐alpha (TNFα) and recombinant human interferon‐gamma (IFNγ) was investigated.TNFαinhibited colony formation of all colony types representing different maturational stages of normal progenitor cells committed to the myeloid lineage with different orders of sensitivity. Blast‐type colonies derived from patients with acute myelogenous leukemia were more sensitive toTNFα inhibition than progenitor cells purified from normal bone marrow or bone marrow from patients with stable‐phase chronic myelogenous leukemia. The response of most colony types toIFNγ was poor. However, whenIFNγ was administered together withTNFα, synergistically enhanced antiproliferative effects were detected in all colony types tested. The antiproliferative action ofIFNγ on myelopoiesis was enhanced in culture by the presence of autologous monocytes, presumedly by inducing endogenous production ofTNFα. However,TNFα seemed to act directly on the progenitor cells themselves to suppress their clonal growth, rather than involving accessory marrow elements such as monocytes and

ISSN:0737-1454    

DOI:10.1002/stem.5530060403

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractA better understanding of the mechanisms involved in the proliferation of splenic colony‐forming units (CFU‐s) during tumor growth is important for the prevention of bone marrow aplasia during chemotherapy. The in vivo growth of EMT6 cells, a colony‐stimulating factor‐secreting mammary tumor, in BALB/c and nude mice resulted in splenomegaly and an increase in the number of splenic granulocyte/macrophage colony‐forming cells (GM‐CFC). Proliferation of CFU‐s, observed in BALB/c mice but not in nude mice, most likely resulted from combined direct and indirect actions of factors secreted by tumor and host cells (in particular helper T cells). These factors were detectable in the serum immediately following tumor cell injection. Thus, the GM‐CFC response to factors secreted by the EMT6 tumors is thymus‐independent while the CFU‐s response is dependent upon the presence of T cells. Finally, we show that EMT6 tumor growth had no effect on the determination of CFU‐s differentiation toward the various

ISSN:0737-1454    

DOI:10.1002/stem.5530060404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractCellulose ester membranes (Millipore©) or polytetrafluoroethylene (Mitex©) membranes were coated with adherent layers taken from Dexter‐type long‐term cultures, 4‐‐5, 8 or 12 weeks after initiation of culture. The cultures were established with marrow taken from untreated mice or, in some cases, from mice treated with a single lethal dose (LD10) of carmustine (BCNU) or cyclophosphamide. In the studies using untreated mice, the cultures went for 8 or 12 weeks and in the drug studies, for 4‐‐5 weeks. The 8 and 12 week cultures were reseeded at 4 weeks. The membranes were implanted into the peritoneal cavities of mice for 3‐‐12 months after which they were removed, fixed, sectioned and stained for histologic study. After 6 months of implantation, about 40% of the membranes coated with cells from non‐drug‐treated mice and 60% of the membranes coated with cells from drug‐treated mice contained hematopoietic elements; often there were foci of trilineal hematopoiesis. Hematopoiesis never occurred without bone formation, but the reverse was not true. Membranes coated with adherent layers established from marrow of mice treated with cyclophosphamide or BCNU showed two main characteristics: 1) they supported hematopoiesis normally, and 2) the regeneration of stroma and hematopoiesis occurred earlier than in membranes coated with stroma derived from normal mice, perhaps because the cells from the drug‐treated mice spent a shorter time in culture. In vitro culture may damage cells required to condition the m

ISSN:0737-1454    

DOI:10.1002/stem.5530060405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThe influence of histamine at various concentrations on the cell cycle state of hematopoietic stem cells (CFU‐s) was investigated. CFU‐s were triggered from the G0state into the S phase of the cell cycle by in vitro treatment of mouse bone marrow cells with high concentrations of histamine. This effect could be antagonized by a histamine H2receptor blocking agent. When bone marrow cells were treated with a histamine H1receptor antagonist prior to histamine treatment, low concentrations of histamine also triggered the entrance of CFU‐s into the DNA synthetic phase. Our findings further suggest the existence of histamine H1and H2receptors on the surface of CFU‐s cells and the antagonistic effect of these two histamine receptor subtypes on the cell cycle state of CFU‐s. Our results also suggest that histamine may participate in regulating the proliferation of hematopoietic stem cells in vivo during immune or inflammatory

ISSN:0737-1454    

DOI:10.1002/stem.5530060406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThe less than self‐evident effect of alterations in cell kinetics on the growth of hemopoietic colonies in the spleens of irradiated mice has important implications for the interpretation of results obtained with this unique multipotential stem cell assay. The effect on colony growth of variation in the principle cell kinetic parameters has been calculated by simulating the growth of spleen colonies so as to provide a guide to the interpretation of experimental results. This data is used to re‐interpret two particular experimental observations on the effect of cytotoxic agents in terms of alterations in the response of stem cells to regulatory factors in place of previous interpretations regarding the differing self‐renewal capacities for subpopulations of stem cells and their sensitivity to various

ISSN:0737-1454    

DOI:10.1002/stem.5530060407

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

ISSN:0737-1454    

DOI:10.1002/stem.5530060408

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY