scholarly journals Identification of immature and mature myeloma cells in the bone marrow of human myelomas

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 564-570 ◽  
Author(s):  
MM Kawano ◽  
N Huang ◽  
H Harada ◽  
Y Harada ◽  
A Sakai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adhesion Molecules ◽  
Proliferative Activity ◽  
M Protein ◽  
Color Analysis ◽  
Myeloma Cells ◽  
A Cell ◽  
Immature Cells ◽  
Human Myeloma Cells

Abstract With regard to the expression of adhesion molecules, human myeloma cells freshly isolated from bone marrow were heterogeneous. By two- color analysis with anti-VLA-5 antibody (PE staining) and FITC-labeled anti-CD38 antibody, we found all myeloma cells located at CD38-strong positive (CD38++) fraction and identified two subpopulations among these myeloma cells: CD38++ VLA-5-(VLA-5-) myeloma cells and CD38++ VLA- 5+ (VLA-5+) myeloma cells. To clarify the biologic character of these two subpopulations, the morphology, in vitro proliferative activity and in vitro M-protein secretion were examined in each fraction isolated by the purification procedure or a cell sorter. Morphologic examination showed that VLA-5- myeloma cells were mostly immature or plasmablastic and VLA-5+ cells were mature myeloma cells. Furthermore, VLA-5- myeloma cells proliferated markedly in vitro and responded to interleukin 6 (IL- 6), a growth factor for myeloma cells, while VLA-5+ myeloma cells showed very low uptakes of 3H-thymidine and no responses to IL-6 but secreted higher amounts of M-protein (immunoglobulin) in vitro significantly. Therefore, we could clarify here heterogeneity of human myeloma cells in the bone marrow with regard to the expression of VLA- 5, one of integrin adhesion molecules; VLA-5- myeloma cells were proliferative immature cells and VLA-5+ cells were mature myeloma cells.

scholarly journals Identification of immature and mature myeloma cells in the bone marrow of human myelomas

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 564-570 ◽  
Author(s):  
MM Kawano ◽  
N Huang ◽  
H Harada ◽  
Y Harada ◽  
A Sakai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adhesion Molecules ◽  
Proliferative Activity ◽  
M Protein ◽  
Color Analysis ◽  
Myeloma Cells ◽  
A Cell ◽  
Immature Cells ◽  
Human Myeloma Cells

With regard to the expression of adhesion molecules, human myeloma cells freshly isolated from bone marrow were heterogeneous. By two- color analysis with anti-VLA-5 antibody (PE staining) and FITC-labeled anti-CD38 antibody, we found all myeloma cells located at CD38-strong positive (CD38++) fraction and identified two subpopulations among these myeloma cells: CD38++ VLA-5-(VLA-5-) myeloma cells and CD38++ VLA- 5+ (VLA-5+) myeloma cells. To clarify the biologic character of these two subpopulations, the morphology, in vitro proliferative activity and in vitro M-protein secretion were examined in each fraction isolated by the purification procedure or a cell sorter. Morphologic examination showed that VLA-5- myeloma cells were mostly immature or plasmablastic and VLA-5+ cells were mature myeloma cells. Furthermore, VLA-5- myeloma cells proliferated markedly in vitro and responded to interleukin 6 (IL- 6), a growth factor for myeloma cells, while VLA-5+ myeloma cells showed very low uptakes of 3H-thymidine and no responses to IL-6 but secreted higher amounts of M-protein (immunoglobulin) in vitro significantly. Therefore, we could clarify here heterogeneity of human myeloma cells in the bone marrow with regard to the expression of VLA- 5, one of integrin adhesion molecules; VLA-5- myeloma cells were proliferative immature cells and VLA-5+ cells were mature myeloma cells.

scholarly journals Separation of human myeloma cells from bone marrow aspirates in multiple myeloma and their proliferation and M-protein secretion in vitro

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 562-566 ◽  
Author(s):  
K Iwato ◽  
M Kawano ◽  
H Asaoku ◽  
O Tanabe ◽  
H Tanaka ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Protein Secretion ◽  
Secretion Rate ◽  
M Protein ◽  
Cell Fraction ◽  
Bone Marrow Mononuclear Cell ◽  
Myeloma Cells ◽  
Human Myeloma Cells

Abstract Human myeloma cells were purified from bone marrow aspirates from patients with multiple myeloma (MM) by Percoll discontinuous density- gradient centrifugation, E rosette formation and treatment with antimyelomonocytic antibody (Leu M1), plus complement. Thus, the purified cell fraction consisted of greater than 90% myeloma cells, even when as little as 15% myeloma cells were contained in bone marrow mononuclear cell fraction, determined by morphological and immunologic examinations. With highly purified myeloma cells from 29 patients with IgG type MM, biologic characteristics such as spontaneous proliferation (3H-TdR uptake) and M-protein secretion rate in vitro were evaluated. Both activities varied among patients within stage I and III, and a 3H- TdR uptake of 255–24, 132 cpm/4 x 10(4) cells, and an M-protein secretion rate of 9 to 72 pg/cell/day, respectively, were recorded. However, in each patient, there was no correlation between 3H-TdR uptake and M-protein secretion rate. These results thus suggest that 3H- TdR uptake and M-protein secretion rate of highly purified myeloma cells are independent biologic parameters, not associated with the clinical stages, and the purification of myeloma cells we describe can contribute to further studies on the biologic characteristics and to understanding of the pathophysiology involved in MM.

scholarly journals Separation of human myeloma cells from bone marrow aspirates in multiple myeloma and their proliferation and M-protein secretion in vitro

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 562-566 ◽  
Author(s):  
K Iwato ◽  
M Kawano ◽  
H Asaoku ◽  
O Tanabe ◽  
H Tanaka ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Protein Secretion ◽  
Secretion Rate ◽  
M Protein ◽  
Cell Fraction ◽  
Bone Marrow Mononuclear Cell ◽  
Myeloma Cells ◽  
Human Myeloma Cells

Human myeloma cells were purified from bone marrow aspirates from patients with multiple myeloma (MM) by Percoll discontinuous density- gradient centrifugation, E rosette formation and treatment with antimyelomonocytic antibody (Leu M1), plus complement. Thus, the purified cell fraction consisted of greater than 90% myeloma cells, even when as little as 15% myeloma cells were contained in bone marrow mononuclear cell fraction, determined by morphological and immunologic examinations. With highly purified myeloma cells from 29 patients with IgG type MM, biologic characteristics such as spontaneous proliferation (3H-TdR uptake) and M-protein secretion rate in vitro were evaluated. Both activities varied among patients within stage I and III, and a 3H- TdR uptake of 255–24, 132 cpm/4 x 10(4) cells, and an M-protein secretion rate of 9 to 72 pg/cell/day, respectively, were recorded. However, in each patient, there was no correlation between 3H-TdR uptake and M-protein secretion rate. These results thus suggest that 3H- TdR uptake and M-protein secretion rate of highly purified myeloma cells are independent biologic parameters, not associated with the clinical stages, and the purification of myeloma cells we describe can contribute to further studies on the biologic characteristics and to understanding of the pathophysiology involved in MM.

scholarly journals Sensitive inhibitory effect of interferon-alpha on M-protein secretion of human myeloma cells

Blood ◽  
1989 ◽  
Vol 74 (5) ◽  
pp. 1718-1722 ◽  
Author(s):  
H Tanaka ◽  
O Tanabe ◽  
K Iwato ◽  
H Asaoku ◽  
H Ishikawa ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Protein Secretion ◽  
Inhibitory Effect ◽  
M Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
In Vitro Proliferation ◽  
Myeloma Cells ◽  
Ifn Alpha ◽  
Human Myeloma Cells

Abstract The effects of interferon-alpha (IFN alpha) on in vitro proliferation and M-protein secretion in human myeloma cells were investigated. Human myeloma cells were purified from bone marrow aspirates in 12 multiple myeloma patients. Purified myeloma cells were cultured for 48 hours with IFN alpha at its lower concentrations (0.1 to 100 U/mL). The cells were then pulsed with 3H-TdR for the last 12 hours and 3H-TdR uptake was measured (in vitro proliferation). After 48-hour culture, supernatants were harvested and the amount of M-protein in these fluids were measured by enzyme-linked immunosorbent assay (ELISA) (in vitro M- protein secretion). In vitro M-protein secretions of myeloma cells were significantly suppressed even at 0.1 U/mL of IFN alpha, while 3H-TdR uptakes were not so suppressed until 10 or 100 U/mL of IFN alpha were added. The expressions of secretory immunoglobulin (Ig) mRNA of these myeloma cells were also selectively suppressed by IFN alpha. Furthermore, after IFN alpha had been administered intramuscularly, 3 to 6 x 10(6) U/d for at least 1 month, in vitro M-protein secretions of these myeloma cells were decreased compared with those before IFN alpha administration. Therefore, these results suggest that IFN alpha has more sensitive inhibitory effect on M-protein secretion of human myeloma cells rather than on myeloma cell proliferation.

scholarly journals Sensitive inhibitory effect of interferon-alpha on M-protein secretion of human myeloma cells

Blood ◽  
1989 ◽  
Vol 74 (5) ◽  
pp. 1718-1722
Author(s):  
H Tanaka ◽  
O Tanabe ◽  
K Iwato ◽  
H Asaoku ◽  
H Ishikawa ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Protein Secretion ◽  
Inhibitory Effect ◽  
M Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
In Vitro Proliferation ◽  
Myeloma Cells ◽  
Ifn Alpha ◽  
Human Myeloma Cells

The effects of interferon-alpha (IFN alpha) on in vitro proliferation and M-protein secretion in human myeloma cells were investigated. Human myeloma cells were purified from bone marrow aspirates in 12 multiple myeloma patients. Purified myeloma cells were cultured for 48 hours with IFN alpha at its lower concentrations (0.1 to 100 U/mL). The cells were then pulsed with 3H-TdR for the last 12 hours and 3H-TdR uptake was measured (in vitro proliferation). After 48-hour culture, supernatants were harvested and the amount of M-protein in these fluids were measured by enzyme-linked immunosorbent assay (ELISA) (in vitro M- protein secretion). In vitro M-protein secretions of myeloma cells were significantly suppressed even at 0.1 U/mL of IFN alpha, while 3H-TdR uptakes were not so suppressed until 10 or 100 U/mL of IFN alpha were added. The expressions of secretory immunoglobulin (Ig) mRNA of these myeloma cells were also selectively suppressed by IFN alpha. Furthermore, after IFN alpha had been administered intramuscularly, 3 to 6 x 10(6) U/d for at least 1 month, in vitro M-protein secretions of these myeloma cells were decreased compared with those before IFN alpha administration. Therefore, these results suggest that IFN alpha has more sensitive inhibitory effect on M-protein secretion of human myeloma cells rather than on myeloma cell proliferation.

scholarly journals A Method for Measurement of Drug Sensitivity of Myeloma Cells Co-Cultured with Bone Marrow Stromal Cells

2013 ◽  
Vol 18 (6) ◽  
pp. 637-646 ◽  
Author(s):  
Kristine Misund ◽  
Katarzyna A. Baranowska ◽  
Toril Holien ◽  
Christoph Rampa ◽  
Dionne C. G. Klein ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Survival ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Large Scale ◽  
Stromal Cell ◽  
Marrow Stromal Cells ◽  
Cell Nuclei ◽  
Myeloma Cells

The tumor microenvironment can profoundly affect tumor cell survival as well as alter antitumor drug activity. However, conventional anticancer drug screening typically is performed in the absence of stromal cells. Here, we analyzed survival of myeloma cells co-cultured with bone marrow stromal cells (BMSC) using an automated fluorescence microscope platform, ScanR. By staining the cell nuclei with DRAQ5, we could distinguish between BMSC and myeloma cells, based on their staining intensity and nuclear shape. Using the apoptotic marker YO-PRO-1, the effects of drug treatment on the viability of the myeloma cells in the presence of stromal cells could be measured. The method does not require cell staining before incubation with drugs, and less than 5000 cells are required per condition. The method can be used for large-scale screening of anticancer drugs on primary myeloma cells. This study shows the importance of stromal cell support for primary myeloma cell survival in vitro, as half of the cell samples had a marked increase in their viability when cultured in the presence of BMSC. Stromal cell–induced protection against common myeloma drugs is also observed with this method.

scholarly journals Percutaneous Exposures of volunteers to polychromatic light (480-3400 nm) trigger systemic mechanism of the human myeloma cells growth delay without any effect on bortezomib cytotoxicity in vitro

LASER THERAPY ◽  
2019 ◽  
Vol 28 (3) ◽  
pp. 164-170
Author(s):  
Natalia V. Kalmykova ◽  
Anna V. Shcherbanyuk ◽  
Sergei I. Moiseev ◽  
Natalia V. Bichkova ◽  
Natalia I. Davidova ◽  
...  
Keyword(s):  
Growth Delay ◽  
Myeloma Cells ◽  
Systemic Mechanism ◽  
Polychromatic Light ◽  
Human Myeloma Cells

Studies on the Clonogenicity of Human Myeloma Cells in vitro

1990 ◽  
Vol 2 (5) ◽  
pp. 271-277
Author(s):  
B. C. Millar ◽  
J. A. Maitland ◽  
J. B. G. Bell ◽  
T. J. McElwain
Keyword(s):  
Myeloma Cells ◽  
Human Myeloma Cells

Granulopoiesis in Shwachman's Syndrome (Pancreatic Insufficiency and Bone Marrow Dysfunction)

PEDIATRICS ◽  
1979 ◽  
Vol 64 (4) ◽  
pp. 515-519
Author(s):  
E. Fred Saunders ◽  
Grant Gall ◽  
Melvin H. Freedman
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Proliferative Activity ◽  
Tritiated Thymidine ◽  
Pancreatic Insufficiency ◽  
Peripheral Blood Lymphocytes ◽  
Exocrine Pancreatic Insufficiency ◽  
Thymidine Uptake ◽  
Blood Leukocytes

Granulopoiesis was studied in 10 children with Shwachman's syndrome (chronic neutropenia and exocrine pancreatic insufficiency). Marrow proliferative activity assessed by determination of mitotic indices and tritiated thymidine uptake into granulocytic cells was normal. Assay of bone marrow granulocyte colony-forming cells (CFU-C) in a methylcellulose tissue culture system demonstrated normal CFU-C numbers in four patients and reduced numbers in five. The granulocyte colonies formed were indistinguishable from normal colonies morphologically. Production of colony-stimulating activity (CSA) from patients' peripheral blood leukocytes appeared normal when tested on control marrow. No serum inhibitors against CFU-C or CSA could be demonstrated using both control and autologous marrow, and co-culture of patients' peripheral blood lymphocytes with control marrow did not inhibit CFU-C growth. We conclude that in Shwachman's syndrome committed granulocytic stem cells are present, and the numbers detected in vitro vary widely as does the clinical neutropenia. The proliferative activity of recognizable granulocytic cells is normal and neither a deficiency of humoral stimulators nor the presence of serum or cellular inhibitors of granulopoiesis can be demonstrated.

Protamine enhances the proliferative activity of hepatocyte growth factor in rats

1998 ◽  
Vol 274 (1) ◽  
pp. G21-G28 ◽  
Author(s):  
Ke-Xin Liu ◽  
Yukio Kato ◽  
Tai-Ichi Kaku ◽  
Kunio Matsumoto ◽  
Toshikazu Nakamura ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Proliferative Activity ◽  
Plasma Clearance ◽  
Mitogenic Response ◽  
Enhancing Effect ◽  
A Cell ◽  
Hepatocyte Growth

The effect of protamine on the proliferative activity of hepatocyte growth factor (HGF) was examined in α-naphthyl isothiocyanate-intoxicated rats. Protamine preinjection increased the hepatocyte labeling index induced by HGF four- to fivefold. A similar effect was also observed in partially hepatectomized rats. Because a cell surface heparin-like substance can bind to HGF and protamine has an affinity for heparin, protamine may affect HGF pharmacokinetics. In fact, protamine injection caused a transient increase in plasma HGF concentrations after administration of HGF and, in vitro, protamine eluted HGF prebound to heparin-Sepharose. Protamine also reduced the plasma clearance of HGF and increased 2.5-fold the exposure of hepatocytes to HGF in vivo. The enhancing effect of protamine on the mitogenic response of hepatocytes to HGF was also observed in vitro (∼2-fold after protamine pretreatment compared with HGF alone), suggesting that the enhancing effect of protamine on HGF-induced liver regeneration results from dual effects exerted by protamine 1) lowering the overall elimination of HGF and 2) directly stimulating hepatocyte mitosis induced by HGF.

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