Cytotoxicityin vitro of blood lymphocytes from bladder cancer patients and controls to allogeneic or autologous tumor cells derived from established cell lines or short-term cultures

1980 ◽  
Vol 25 (1) ◽  
pp. 33-43 ◽  
Author(s):  
M. Troye ◽  
M. Vilien ◽  
G. R. Pape ◽  
P. Perlmann
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Cell Lines ◽  
Autologous Tumor ◽  
Short Term ◽  
Blood Lymphocytes ◽  
Established Cell Lines ◽  
Established Cell

scholarly journals Lymphokine-activated killer cell functions in patients with leukemic B- lymphoproliferative diseases

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2464-2470 ◽  
Author(s):  
D van der Harst ◽  
A Brand ◽  
SA van Luxemburg-Heys ◽  
EM Kooy-Winkelaar ◽  
JJ van Rood
Keyword(s):  
B Cells ◽  
Tumor Cells ◽  
Cell Lines ◽  
Lak Cells ◽  
Autologous Tumor ◽  
Nk Activity ◽  
Malignant Cells ◽  
Lymphoproliferative Diseases ◽  
Short Term

Abstract Nine patients with leukemic B-lymphoproliferative diseases (B-LPD) were evaluated for development of in vitro recombinant interleukin-2 (rIL-2)- activated killer (LAK) cells. B-cell cultures were established from peripheral blood mononuclear cells (PBMNCs) containing 63% +/- 29% malignant cells. Short-term cultures were tested after 5-day activation with 500 U rIL-2/mL. Long-term cultures were maintained for 4 to 6 weeks by weekly addition of 500 U rIL-2 and autologous irradiated feeder cells. In the first week, the cells decreased considerably in the long-term cultures but thereafter cells proliferated (mainly T cells) on the average 300-fold (range 30- to 1,000-fold). In the short- term cultures, there was a 36% reduction of malignant B cells. In long- term cultures, B cells were reduced from 63% to 8%; three cultures still contained greater than 15% B cells. The CD16-positive cell percentage was comparable in both types of cultures and ranged from 2% to 17%. Effector cells lysing the natural killer (NK)-sensitive cell line K562 could be induced in all patients. Except in patients with chronic lymphocytic leukemia (CLL) and high malignant cell numbers, NK activity was already restored after 5 days. Optimal NK activity was obtained after 1.5 to 2.5 weeks. LAK cells killing NK-resistant lymphoma cell lines showed optimal activity after 2 to 3 weeks of culture. However, LAK cells killing greater than 10% of autologous malignant cells were obtained in only one third of the patients. The discrepancy between strong cytolytic activity against the NK-sensitive (K562) target cells obtained in all patients and the cytotoxic activity against NK-resistant cell lines contrasts with the poor development of LAK cells against autologous tumor cells. This discrepancy does not appear to be explained by soluble inhibitory factors released during the tumor cultures, as allogeneic LAK cells were not inhibited by supernatants from patients cultures. Further investigations are warranted to reveal cell-mediated inhibition by tumor cells or suppressor cells.

OBSERVATIONS ON THE EFFECTS OF METHANOL AND FORMALDEHYDE ON ESTABLISHED CELL LINES CULTIVATED IN VITRO

1963 ◽  
Vol 41 (2) ◽  
pp. 299-304 ◽  
Author(s):  
Alice Elliott ◽  
Donald M. Pace
Keyword(s):  
Cell Lines ◽  
Mouse Liver ◽  
Human Lung ◽  
Liver Cells ◽  
Short Term ◽  
Skin Cells ◽  
Established Cell Lines ◽  
Established Cell ◽  
High Concentrations

Short-term experiments were used to investigate the effects of various concentrations of methanol and formaldehyde upon cells grown in vitro. Mouse liver epithelial, HeLa, human lung, and skin cells were exposed to several concentrations of methanol. The same cell lines, except HeLa, were subjected to different concentrations of formaldehyde.Relatively high concentrations of methanol were required to produce rapid toxic effects. Not all cell lines responded alike to methanol. Concentrations of 15 mg/ml were decidedly inhibitory in case of human skin, lung, and HeLa cells. This concentration, however, appeared to enhance growth in liver cells. At higher concentrations the methanol was toxic to liver cells as well as to the others.Concentrations of formaldehyde greater than 0.035 mg/ml were toxic to mouse liver, human lung and skin cells. A concentration of 0.01 mg/ml of formaldehyde inhibited proliferation of these same cells. These three cell lines did not appear to differ significantly in respect to their sensitivity to formaldehyde. Of the substances investigated to date, formaldehyde appears to be the most toxic.

scholarly journals Lymphokine-activated killer cell functions in patients with leukemic B- lymphoproliferative diseases

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2464-2470
Author(s):  
D van der Harst ◽  
A Brand ◽  
SA van Luxemburg-Heys ◽  
EM Kooy-Winkelaar ◽  
JJ van Rood
Keyword(s):  
B Cells ◽  
Tumor Cells ◽  
Cell Lines ◽  
Lak Cells ◽  
Autologous Tumor ◽  
Nk Activity ◽  
Malignant Cells ◽  
Lymphoproliferative Diseases ◽  
Short Term

Nine patients with leukemic B-lymphoproliferative diseases (B-LPD) were evaluated for development of in vitro recombinant interleukin-2 (rIL-2)- activated killer (LAK) cells. B-cell cultures were established from peripheral blood mononuclear cells (PBMNCs) containing 63% +/- 29% malignant cells. Short-term cultures were tested after 5-day activation with 500 U rIL-2/mL. Long-term cultures were maintained for 4 to 6 weeks by weekly addition of 500 U rIL-2 and autologous irradiated feeder cells. In the first week, the cells decreased considerably in the long-term cultures but thereafter cells proliferated (mainly T cells) on the average 300-fold (range 30- to 1,000-fold). In the short- term cultures, there was a 36% reduction of malignant B cells. In long- term cultures, B cells were reduced from 63% to 8%; three cultures still contained greater than 15% B cells. The CD16-positive cell percentage was comparable in both types of cultures and ranged from 2% to 17%. Effector cells lysing the natural killer (NK)-sensitive cell line K562 could be induced in all patients. Except in patients with chronic lymphocytic leukemia (CLL) and high malignant cell numbers, NK activity was already restored after 5 days. Optimal NK activity was obtained after 1.5 to 2.5 weeks. LAK cells killing NK-resistant lymphoma cell lines showed optimal activity after 2 to 3 weeks of culture. However, LAK cells killing greater than 10% of autologous malignant cells were obtained in only one third of the patients. The discrepancy between strong cytolytic activity against the NK-sensitive (K562) target cells obtained in all patients and the cytotoxic activity against NK-resistant cell lines contrasts with the poor development of LAK cells against autologous tumor cells. This discrepancy does not appear to be explained by soluble inhibitory factors released during the tumor cultures, as allogeneic LAK cells were not inhibited by supernatants from patients cultures. Further investigations are warranted to reveal cell-mediated inhibition by tumor cells or suppressor cells.

scholarly journals SIRPαFc, a CD47-Blocking Cancer Immunotherapeutic, Sensitizes Malignant B Cells to Macrophage-Mediated Destruction

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2191-2191
Author(s):  
Natasja Nielsen Viller ◽  
Saman Maleki Vareki ◽  
Karen Dodge ◽  
Hui Chen ◽  
Vivian Lee ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Research Funding ◽  
B Lymphoma ◽  
Established Cell Lines ◽  
Established Cell

Abstract Macrophages commonly infiltrate tumor microenvironments and can phagocytose and destroy malignant cells. Cancer cells, however, can inhibit the tumoricidal activity of macrophages by expressing CD47 on their surface. CD47 delivers an anti-phagocytic ("do not eat") signal by binding signal-regulatory protein α (SIRPα) on the surface of macrophages. There is strong evidence that many liquid and solid tumors exploit the CD47-SIRPα pathway to escape macrophage-mediated destruction. Blockade of this inhibitory axis using a soluble SIRPα-Fc fusion protein (SIRPαFc) has emerged as a promising strategy to neutralize the suppressive effects of CD47 and promote the eradication of tumor cells. Here we have examined the effect of SIRPαFc on malignant human B cells in vitro and in vivo. We first assessed the binding of SIRPαFc to a panel of established cell lines and primary cells from patients with diffuse large B cell lymphoma, Burkitt's lymphoma, multiple myeloma and acute lymphoblastic leukemia. SIRPαFc exhibited strong, dose-dependent binding to all tumor cells, with an average effective half-maximal concentration of approximately 150 nM. Next, the ability of SIRPαFc to promote macrophage-mediated phagocytosis of human tumor cells was examined using confocal microscopy. In cultures left untreated or treated with a control Fc fragment, macrophages exhibited a low level of phagocytosis, consistent with CD47-mediated suppression. Blockade of CD47 on the target cells using SIRPαFc dramatically increased macrophage phagocytosis of tumor cells. The majority of established cell lines and all primary human tumors were sensitized to macrophage-mediated destruction, including both peripheral blood- and bone marrow-derived primary tumor samples. Finally, we assessed the in vivo activity of SIRPαFc in CD20hi (Raji) and CD20low (Namalwa) B lymphoma xenograft models. SIRPαFc treatment significantly reduced Raji growth and increased host mouse survival (time to euthanasia), and completely ablated the growth of Namalwa tumors, the latter being insensitive to rituximab therapy. In conclusion, SIRPαFc demonstrated in vitro activity against a broad range of human B cell tumors and was highly effective at controlling the growth of aggressive B lymphoma xenografts in mice, including a CD20low tumor that was non-responsive to rituximab. These data support the evaluation of SIRPαFc in patients with B cell malignancies. Disclosures Nielsen Viller: Trillium Therapeutics Inc.: Employment. Vareki:Trillium Therapeutics Inc.: Research Funding. Dodge:Trillium Therapeutics Inc.: Employment. Chen:Trillium Therapeutics Inc.: Employment. Lee:Trillium Therapeutics Inc.: Employment. Chai:Trillium Therapeutics Inc.: Employment. Pang:Trillium Therapeutics Inc.: Employment. Wong:Trillium Therapeutics Inc.: Employment. Trudel:Novartis: Honoraria; Oncoethix: Research Funding; BMS: Honoraria; Trillium Therapeutics Inc.: Research Funding; Celgene: Equity Ownership, Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Figueredo:Trillium Therapeutics Inc.: Research Funding. Pampillo:Trillium Therapeutics Inc.: Research Funding. Koropatnick:Trillium Therapeutics Inc.: Research Funding. Petrova:Trillium Therapeutics Inc.: Employment. Uger:Trillium Therapeutics Inc.: Employment.

OBSERVATIONS ON THE EFFECTS OF METHANOL AND FORMALDEHYDE ON ESTABLISHED CELL LINES CULTIVATED IN VITRO

1963 ◽  
Vol 41 (1) ◽  
pp. 299-304
Author(s):  
Alice Elliott ◽  
Donald M. Pace
Keyword(s):  
Cell Lines ◽  
Mouse Liver ◽  
Human Lung ◽  
Liver Cells ◽  
Short Term ◽  
Skin Cells ◽  
Established Cell Lines ◽  
Established Cell ◽  
High Concentrations

Short-term experiments were used to investigate the effects of various concentrations of methanol and formaldehyde upon cells grown in vitro. Mouse liver epithelial, HeLa, human lung, and skin cells were exposed to several concentrations of methanol. The same cell lines, except HeLa, were subjected to different concentrations of formaldehyde.Relatively high concentrations of methanol were required to produce rapid toxic effects. Not all cell lines responded alike to methanol. Concentrations of 15 mg/ml were decidedly inhibitory in case of human skin, lung, and HeLa cells. This concentration, however, appeared to enhance growth in liver cells. At higher concentrations the methanol was toxic to liver cells as well as to the others.Concentrations of formaldehyde greater than 0.035 mg/ml were toxic to mouse liver, human lung and skin cells. A concentration of 0.01 mg/ml of formaldehyde inhibited proliferation of these same cells. These three cell lines did not appear to differ significantly in respect to their sensitivity to formaldehyde. Of the substances investigated to date, formaldehyde appears to be the most toxic.

scholarly journals MMP-7 Serum and Tissue Levels Are Associated with Poor Survival in Platinum-Treated Bladder Cancer Patients

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 48
Author(s):  
Tibor Szarvas ◽  
Michèle J. Hoffmann ◽  
Csilla Olah ◽  
Eszter Szekely ◽  
Andras Kiss ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Checkpoint Inhibitors ◽  
Serum Concentrations ◽  
Serum Samples ◽  
Poor Overall Survival ◽  
Platinum Sensitivity ◽  
Therapeutic Decisions ◽  
Platinum Based Chemotherapy

Chemotherapy resistance is a main cause of therapeutic failure and death in bladder cancer. With the approval of immune checkpoint inhibitors, prediction of platinum treatment became of great clinical importance. Matrix metalloproteinase-7 (MMP-7) was shown to be involved in cisplatin resistance. Therefore, tissue and circulating MMP-7 levels were evaluated in 124 bladder cancer patients who received postoperative platinum-based chemotherapy. Tissue MMP-7 levels were analyzed by immunohistochemistry in 72 formalin-fixed, paraffin-embedded chemo-naïve tumor samples, while MMP-7 serum concentrations were determined in 132 serum samples of an independent cohort of 52 patients. MMP-7 tissue and serum levels were correlated with clinicopathological and follow-up data. MMP-7 gene expression was determined by RT-qPCR in 20 urothelial cancer cell lines and two non-malignant urothelial cell lines. MMP-7 was overexpressed in RT-112 and T-24 cells by stable transfection, to assess its functional involvement in platinum sensitivity. High MMP-7 tissue expression and pretreatment serum concentrations were independently associated with poor overall survival (tissue HR = 2.296, 95%CI = 1.235–4.268 and p = 0.009; serum HR = 2.743, 95%CI = 1.258–5.984 and p = 0.011). Therefore, MMP-7 tissue and serum analysis may help to optimize therapeutic decisions. Stable overexpression in RT-112 and T-24 cells did not affect platinum sensitivity.

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