摘要:

AbstractThe human tumor stem cell (clonogenic) assay (HTCA) is a soft agar system designed for growing fresh human tumor specimens in vitro. The assay has been extensively used in studies both of individual patients' response to chemotherapy and for screening new agents. The technical limitations of this assay have been extensively discussed. The use of this test as a model system to study fundamentals of tumor cell growth has not been stressed. The potentials and limitations of this assay for the study of the regulation of tumor growth are presented.

ISSN:0737-1454    

DOI:10.1002/stem.5530050202

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

年代:1987

数据来源: WILEY

摘要:

AbstractInformation about the differentiation of mast cells has increased remarkably in the past ten years. This progress has resulted from the introduction of techniques which developed in other fields of experimental hematology. Once mast cells were recognized as a progeny of multipotential hematopoietic stem cells, their unique differentiation processes were clarified. Although most of the progeny of stem cells leave the hematopoietic tissue after maturation, undifferentiated precursors of mast cells leave the hematopoietic tissue. Morphologically, unidentifiable precursors migrate in the bloodstream, invade the connective tissues or the mucosa of the alimentary canal, proliferate, and differentiate into mast cells. Even after their morphological differentiation, some mast cells retain an extensive proliferative potential. There are at least two subpopulations of mast cells: a connective‐tissue type and a mucosal type. Connective tissue‐type and mucosal mast cells can be distinguished by histochemical, electron microscopical, biochemical and immunological criteria; however, these two types can interchange, and their phenotypes are determined by the anatomical microenvironment in which their final differentiation occurs. Although biochemical natures of the anatomical microenvironment are unknown, molecules that support proliferation and differentiation of mast cells in vitro have been characterized, i.e., interleukin 3 and interleukin 4. In the next ten years, increased information about the differentiation processes will probably induce further understanding of mast cell functi

ISSN:0737-1454    

DOI:10.1002/stem.5530050203

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

年代:1987

数据来源: WILEY

摘要:

AbstractSuppression of hematopoiesis is far too often the main consequence of antineoplastic therapy, such that the developing degree of myelosuppression and/or thrombocytopenia are usually the rate‐limiting steps to adjuvant therapy. This communication reports the results of studies designed to investigate the capability of lithium to accelerate in vivo hematopoietic recovery following exposure to vinblastine sulfate (VB). Male mice (144 BC3F1) received VB (4 mg/kg/b.w.) i.v. Twenty‐four h following VB, 72 mice received 35 μgm/animal, ultra‐pure lithium carbonate (Li2CO3) i.p. Another 72 mice received either VB or phosphate buffered saline as controls. Beginning 24 h later and continuing on days 2, 5, 7, 9, 12, 21 and 28, three mice from each group were randomly sacrificed and their hematological parameters analyzed. Bone marrow and splenic granulocyte‐macrophage progenitor cells (CFU‐gm) and megakaryocyte progenitor cells (CFU‐meg) content were evaluated. Lithium was unable to prevent the onset of either neutropenia or thrombocytopenia; however, lithium was successful in restoring normal white blood cell and platelet values earlier than the VB control group, thus significantly reducing the period of drug‐induced neutropenia and thrombocytopenia. This lithium‐enhanced hematopoiesis was measured by an accelerated recovery in both marrow and splenic CFU‐gm and CFU‐meg compared to controls. These data demonstrate the efficacy of lithium to accelerate hematopoietic recovery following exposure to cytotoxic

ISSN:0737-1454    

DOI:10.1002/stem.5530050204

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

年代:1987

数据来源: WILEY

摘要:

AbstractRemarkable differences were found between late erythroid progenitors (CFU‐e) in cultures of murine yolk sac cells and those of fetal liver cells with respect to frequency, erythropoietin responsiveness and colony size. Cultures of yolk sac on day 11 of gestation showed a CFU‐e population of lower frequency, less sensitivity to erythropoietin and smaller colony size than those from cultures of day 14 fetal liver cells.As the proportion of CFU‐e to BFU‐e was much lower in yolk sac than that in fetal liver, 48–96 h liquid culture experiments were done with these cells to examine the capacity of their precursors to generate a certain amount of CFU‐e subpopulations. The cultures of yolk sac cells produced large numbers of CFU‐e which formed some large‐sized colonies but those of fetal liver cells generated only a small

ISSN:0737-1454    

DOI:10.1002/stem.5530050205

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

年代:1987

数据来源: WILEY

摘要:

AbstractWhen seeded at low‐density, normal primary explanted granulosa cells will grow to form clones of functionally differentiated cells in both semisolid agar and in liquid culture. The anchorage‐independent clonogenic granulosa cell differs from the anchorage‐dependent granulosa cells detected in clonal liquid culture in a number of properties. 1) Basal cloning efficiency in liquid culture is up to 50‐fold higher than in agar culture. 2) In serum supplemented medium (20% fetal calf serum) cloning efficiency in liquid culture is unaltered in the presence of added epidermal growth factor (EGF), whereas, agar cloning efficiency is augmented six‐fold when cells are incubated under identical conditions. 3) Cells derived from primary anchorage‐independent clones, when dispersed and replated, will generate secondary anchorage‐independent clones and anchorage‐dependent liquid clones. On the other hand, although cells derived from parallel primary anchorage‐dependent clones will also generate secondary anchorage‐dependent clones, generation of secondary anchorage‐independent clones is not detectable. These findings suggest that the anchorage‐independent clonal agar assay may be detecting a developmentally earlier granulosa cell subpopulation than is detectable in t

ISSN:0737-1454    

DOI:10.1002/stem.5530050206

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

年代:1987

数据来源: WILEY

摘要:

AbstractCytotoxic drug sensitivity of normal human lymphocytes and malignant lymphocytes was estimated by a clonogenic method. Malignant T and B lymphocytes were relatively more sensitive than normal T lymphocytes to vincristine and Adriamycin. Since no plateau was observed in the clone survival with associated increasing drug concentration, spontaneous mutants could not be detected. It is suggested that the resistance to “natural product” drugs such as vincristine arises from induced mutations and not from the selection of already existing spontaneous muta

ISSN:0737-1454    

DOI:10.1002/stem.5530050207

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

年代:1987

数据来源: WILEY

摘要:

AbstractWe studied the factors that control the capacity of tumor cells to grow in soft agar. And, we analyzed the effect of cell‐free ascites (CFA) obtained from ovarian cancer patients in combination with various media on the cloning efficiency of H‐134 and OVCAR‐3nuovarian carcinoma cell lines and the WiDr colon carcinoma cell line.Seven batches of CFA consistently enhanced the soft agar growth of tumor cells more efficiently than tested sera. The addition of charcoal‐treated bovine serum albumin (BSA) lowered the amount of CFA required for optimal tumor cell growth. As little as 1.25 ng of epidermal growth factor (EGF)/ml further improved OVCAR‐3nusoft agar growth in combination with all of the amounts of CFA tested. Thus, neither BSA nor EGF seems to account for the colony‐stimulating effect of ascites on tumor cells.Four batches of CFA were tested for stimulating soft agar growth of normal rat kidney (NRK‐49F) fibroblasts; all induced colonies of different morphologies. This effect was potentiated by EGF, which suggests the presence of several transforming growth factorlike activities in CFA.The results show that differences in cloning efficiency of tumor cells of one or two orders of magnitude can be found between standard (anchorage‐dependent growth‐supporting) media and media optimalized for soft agar growth, such as CFA in the presence of EGF. This paper will discuss the similarity in effects of CFA on various tumor cells and NRK cells, and possible implications of the stimulato

ISSN:0737-1454    

DOI:10.1002/stem.5530050208

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

年代:1987

数据来源: WILEY

摘要:

AbstractVanadium is a trace element widely distributed in nature. It interferes with a variety of enzyme systems and is also reported to increase DNA‐synthesis and in vitro clonal growth of human and mouse fibroblasts. The purpose of the present study was to determine the effect of vanadium salts on the in vitro growth of fresh human tumor specimens. Various concentrations of ammonium metavanadate (AMV), vanadyl sulfate trihydrate (VST) and ortho sodium vanadate (OSV) were tested in a human tumor cloning assay (HTCA). Thirty‐four evaluable specimens were tested at concentrations of ≥ 10‐10Mof one or more vanadium salts. At this concentration, colony formation was increased by ≥ 150% as compared to control at one or more concentrations in 16 specimens (47%). Twelve evaluable specimens were tested against various concentrations>10‐10M.Colony formation was inhibited by ≥ 50% of the control at one or more concentrations in all specimens. In further experiments we performed a head‐to‐head comparison of OSV (10‐3M) and our standard positive control for cell kill (chromomycin A3, 100 μg/ml) in 34 specimens. OSV led to a comparable or better cell kill in 28 tumors (82%). We conclude that vanadium salts at low concentrations (≥ 10‐10M) can stimulate in vitro colony formation from human tumors. At higher concentrations (>10‐10M) tumor colony formation is inhibited. OSV might be useful as a very inexpensive positive control in the HTCA. In addition, the value of vanadium salts as antitumor agents should be fu

ISSN:0737-1454    

DOI:10.1002/stem.5530050209

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

年代:1987

数据来源: WILEY

ISSN:0737-1454    

DOI:10.1002/stem.5530050210

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

年代:1987

数据来源: WILEY

ISSN:0737-1454    

DOI:10.1002/stem.5530050201

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

年代:1987

数据来源: WILEY