Biomaterial Database

Effects of scheduling and ascites-associated macrophages on combined antiproliferative activity of alpha-2b interferon and gamma-interferon in a clonogenic assay. 1988

J Higashihara, and T Saito, and M E Berens, and C E Welander

Section on Gynecologic Oncology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27103.

Effects of combination treatment with human recombinant alpha-2b interferon (IFN-alpha 2b) and gamma interferon (IFN-gamma) and sequencing of the combination on colony formation of human tumor cells were studied in a human tumor clonogenic assay (HTCA) with or without ascites-associated macrophages (AAM). Five different human tumor cell lines were studied. Three of the five cell lines (ovarian cancer cell line BG-1, cervical cancer cell line ME-180, and melanoma cell line SK-MEL 28) were sensitive to both IFNs. Cervical cancer cell line CaSki was sensitive to IFN-alpha 2b but resistant to IFN-gamma. Endometrial cancer cell line HEC-1A was resistant to both IFNs. Synergistic interaction was observed in BG-1 and SK-MEL 28 with a combination of the IFNs. ME-180 did not exhibit a positive interaction, in spite of its sensitivity to each IFN. CaSki and HEC-1A also did not exhibit a positive combined interaction at clinically achievable concentrations. One sequential combination method (method 1: IFN-alpha 2b----IFN gamma with a 24-h interval) resulted in a similar antitumor effect as the simultaneous combination. A reversed sequential method (method 2: IFN-gamma----IFN-alpha 2b with a 24-h interval) was less effective in three of the five cell lines. In BG-1, AAM enclosed in the lower layer markedly enhanced the antitumor effect of combined IFNs as well as each IFN alone. The antitumor effect with method 1 was significantly greater than that achieved with simultaneous combination or combination according to method 2 in the presence of AAM (P less than 0.01). These results suggest that (1) a synergistic antitumor effect of IFN-alpha 2b and IFN gamma is demonstrable in selected types of tumors, depending upon the sensitivity of each tumor cell line to both IFNs; (2) optimal scheduling for the direct antitumor effect of combined IFNs seems to be long-term exposure of cells to the IFN, the cells being treated with both IFNs either simultaneously or sequentially (IFN-alpha 2b preceding IFN-gamma); and (3) AAM potentiate the antitumor effect of IFNs either alone or in combination. Finally, IFN-alpha 2b may have some priming effects for the indirect effect of IFN gamma mediated through AAM in certain tumor cells.

UI	MeSH Term	Description	Entries
D007370	Interferon Type I	Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).	Interferons Type I,Type I Interferon,Type I Interferons,Interferon, Type I,Interferons, Type I
D007371	Interferon-gamma	The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.	Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D008264	Macrophages	The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)	Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D010051	Ovarian Neoplasms	Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.	Cancer of Ovary,Ovarian Cancer,Cancer of the Ovary,Neoplasms, Ovarian,Ovary Cancer,Ovary Neoplasms,Cancer, Ovarian,Cancer, Ovary,Cancers, Ovarian,Cancers, Ovary,Neoplasm, Ovarian,Neoplasm, Ovary,Neoplasms, Ovary,Ovarian Cancers,Ovarian Neoplasm,Ovary Cancers,Ovary Neoplasm
D002455	Cell Division	The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.	M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D003114	Colony-Forming Units Assay	A cytologic technique for measuring the functional capacity of stem cells by assaying their activity.	Clonogenic Cell Assay,Stem Cell Assay,Clonogenic Cell Assays,Colony Forming Units Assays,Colony-Forming Units Assays,Stem Cell Assays,Assay, Clonogenic Cell,Assay, Colony-Forming Units,Assay, Stem Cell,Assays, Clonogenic Cell,Assays, Colony-Forming Units,Assays, Stem Cell,Colony Forming Units Assay
D003131	Combined Modality Therapy	The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used.	Multimodal Treatment,Therapy, Combined Modality,Combined Modality Therapies,Modality Therapies, Combined,Modality Therapy, Combined,Multimodal Treatments,Therapies, Combined Modality,Treatment, Multimodal,Treatments, Multimodal
D004334	Drug Administration Schedule	Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.	Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man