Adaptation of Columbia SK Virus to Sarcoma 180 Ascites Tumor Cells in vivo and Passage in the Cells in vitro.

1961 ◽  
Vol 108 (1) ◽  
pp. 244-248
Author(s):  
E. Furusawa ◽  
W. Cutting
Keyword(s):  
Tumor Cells ◽  
Sarcoma 180 ◽  
Ascites Tumor

THE FORMATION OF 6-MERCAPTOPURINE RIBOSIDE PHOSPHATE IN ASCITES TUMOR CELLS

1959 ◽  
Vol 37 (8) ◽  
pp. 1011-1023 ◽  
Author(s):  
A. R. P. Paterson
Keyword(s):  
Tumor Cells ◽  
Solid Tumor ◽  
Carcinoma Cells ◽  
Sarcoma 180 ◽  
Ascites Tumor ◽  
Enzymatic Methods

A nucleotide metabolite of 6-mercaptopurine has been isolated from Erhlich ascites carcinoma cells exposed to this compound under in vivo and in vitro conditions. By chemical and enzymatic methods, this nucleotide has been identified as 6-mercaptopurine nucleoside-5′-monophosphate.6-Mercaptopurine nucleotide is formed rapidly in the tumor cells in vivo, maximum concentrations being achieved within 0.5 hours after administration of the analogue. Treatment of the tumor cells with 6-mercaptopurine or with azaserine induced a twofold to threefold enhancement in their ability to synthesize 6-mercaptopurine nucleotide.Using isotopic techniques small amounts of 6-mercaptopurine nucleotide were detected in liver, intestine, and a solid tumor. The conversion of 6-mercaptopurine to the nucleotide form was also demonstrated in an ascitic form of Sarcoma 180.

THE FORMATION OF 6-MERCAPTOPURINE RIBOSIDE PHOSPHATE IN ASCITES TUMOR CELLS

1959 ◽  
Vol 37 (1) ◽  
pp. 1011-1023 ◽  
Author(s):  
A. R. P. Paterson
Keyword(s):  
Tumor Cells ◽  
Solid Tumor ◽  
Carcinoma Cells ◽  
Sarcoma 180 ◽  
Ascites Tumor ◽  
Enzymatic Methods

A nucleotide metabolite of 6-mercaptopurine has been isolated from Erhlich ascites carcinoma cells exposed to this compound under in vivo and in vitro conditions. By chemical and enzymatic methods, this nucleotide has been identified as 6-mercaptopurine nucleoside-5′-monophosphate.6-Mercaptopurine nucleotide is formed rapidly in the tumor cells in vivo, maximum concentrations being achieved within 0.5 hours after administration of the analogue. Treatment of the tumor cells with 6-mercaptopurine or with azaserine induced a twofold to threefold enhancement in their ability to synthesize 6-mercaptopurine nucleotide.Using isotopic techniques small amounts of 6-mercaptopurine nucleotide were detected in liver, intestine, and a solid tumor. The conversion of 6-mercaptopurine to the nucleotide form was also demonstrated in an ascitic form of Sarcoma 180.

Attenuation of cytogenetic effects by erythropoietin in human lymphocytes in vitro and P388 ascites tumor cells in vivo treated with irinotecan (CPT-11)

2010 ◽  
Vol 48 (1) ◽  
pp. 242-249 ◽  
Author(s):  
E. Digkas ◽  
D. Kareli ◽  
S. Chrisafi ◽  
T. Passadaki ◽  
E. Mantadakis ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Human Lymphocytes ◽  
Ascites Tumor ◽  
Cytogenetic Effects

scholarly journals RELATION BETWEEN WATER PERMEABILITY AND INTEGRITY OF SULFHYDRYL GROUPS IN MALIGNANT AND NORMAL CELLS

1961 ◽  
Vol 9 (4) ◽  
pp. 733-745 ◽  
Author(s):  
Morris Belkin ◽  
Walter G. Hardy
Keyword(s):  
Tumor Cells ◽  
Cell Lines ◽  
Intraperitoneal Administration ◽  
Malignant Cell ◽  
Sulfhydryl Groups ◽  
Ascites Tumor ◽  
Protein Sulfhydryl ◽  
Protein Sulfhydryl Groups

When malignant cells, animal and human, were exposed in vitro to solutions of heavy metals or other selected compounds, three types of cell blebs were produced: (1) acentric blebs, arising from one side of the cell, e. g., by chlormerodrin, meralluride sodium, mercuric chloride; (2) symmetrical blebs; which completely enveloped the cell, e. g., by strong silver protein, auric chloride, p-chloromercuribenzoate; (3) scallop blebs, numerous small spherical elevations which completely covered the cell, e.g., by N-ethyl-maleimide, trivalent arsenicals, iodoacetamide. As indicated by vital stains and morphologic appearance, the blebs arose in healthy cells. They also can be made to appear in vivo in ascites tumor cells by intraperitoneal administration of a blebbing agent. All the bleb-producing chemicals have the property of reacting with protein-sulfhydryl groups by alkylation, oxidation or mercaptide formation. The three bleb types have been induced in 8 mouse and 2 rat ascites tumor cells; in 4 human and 1 mouse malignant cell lines; and in 3 normal cell lines grown in tissue culture. In contrast, cells from normal solid tissues of liver, lung, spleen, kidney, testis and brain from mouse, rat and rabbit failed to produce blebs. A possible interpretation for these observations is presented.

Efficacy of LY2784544, a Small Molecule Inhibitor Selective for Mutant JAK2 Kinase, In JAK2 V617F-Induced Hematologic Malignancy Models

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4087-4087 ◽  
Author(s):  
Liandong Ma ◽  
Baohui Zhao ◽  
Richard Walgren ◽  
Joshua A Clayton ◽  
Wayne D Blosser ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Tumor Cells ◽  
Oral Treatment ◽  
Jak2 V617f ◽  
Tumor Burden ◽  
Ascites Tumor ◽  
Wild Type ◽  
Erythroid Progenitor

Abstract Abstract 4087 Introduction: The JAK2-V617F mutation is the most common molecular abnormality in the BCR/ABL-negative myeloid proliferative neoplasms (MPNs) and is present in approximately 95% of patients with polycythemia vera (PV) and roughly 60% of patients with either essential thrombocythemia (ET) or primary myelofibrosis (PMF). The JAK2 V617F kinase is constitutively active, oncogenic and recapitulates MPN in murine models. Therefore, mutant JAK2 is a potential therapeutic target for MPNs. Here, we describe the efficacy of the clinical candidate LY2784544; a novel small molecule inhibitor selective for JAK2 V617F mutant, in JAK2 V617F-induced in vitro and in vivo models. Methods: Assessment of the ability of LY2784544 to inhibit the signaling of the V617F mutant or wild type JAK2 was evaluated in Ba/F3 cells expressing V617F or wild type JAK2, whereby the cellular level of phospho-STAT5 (pSTAT5) was measured by a high content imaging (Cellomics) assay. The antiproliferative activity of LY2784544 and its ability to induce apoptosis were examined by Celltiter-Glo Cell Viability and Caspase-Glo 3/7 Apoptosis Assays, respectively. The effect of LY2784544 on JAK3 was investigated in IL-2 stimulated NK-92 (nature killer) cells by measuring the inhibition of JAK3-STAT5 signaling with the Cellomics assay. To examine the in vivo target inhibition, a JAK2 V617F-induced ascites tumor model was established by implanting Ba/F3-JAK2 V617F-GFP cells into the intraperitoneal cavity of severe combined immunodeficiency (SCID) mice. After orally administering LY2784544, the inhibition of pSTAT5 was measured in Ba/F3-JAK2 V617F-GFP ascites tumor cells by fluorescence activated cell sorting (FACS) assay. The anti-tumor efficacy of LY2784544 was investigated in a SCID mouse model of MPN developed by intravenously implanting Ba/F3-JAK2 V617F-GFP cells. After oral treatment for 7 or 14 days, twice daily (BID), tumor burden reduction and the effect on erythroid progenitor cells were determined by measuring the GFP positive tumor cells and CD71/Ter119 positive cells in the spleens with FACS assays, respectively. Results: In the in vitro tests using Ba/F3 cells expressing either wild type or V617F mutant JAK2, LY2784544 potently inhibited the JAK2 V617F-STAT5 signaling at a concentration that was 41-fold lower than that required to inhibit IL-3-activated wild type JAK2-STAT5 signaling (IC50=0.055 μ M for JAK2 V617F vs. 2.26 μ M for WT JAK2). Similarly in the proliferation assay, LY2784544 selectively inhibited the JAK2 V617F-driven cell proliferation (IC50= 0.068 μ M). Inhibition of JAK2 V617F signaling correlated well with the induction of apoptosis (EC50= 0.113 μ M) in Ba/F3 cell model. Consistent with the observed apparent selectivity for the V617F mutant and reduced sensitivity against wild type JAK2, a lower potency was observed with LY2784544 in the IL-3-dependent cell proliferation assay (IC50=1.356 μ M) as well as less effective inhibition of IL-2 dependent JAK3-STAT5 signaling in NK-92 cells (IC50=0.94 μ M). In vivo, LY2784544 effectively inhibited STAT5 phosphorylation in Ba/F3-JAK2 V617F-GFP ascites tumor cells with a Threshold Effective Dose 50 (TED50) of 12.7 mg/kg. Consistent with this effective inhibition of JAK2V617F, LY2784544 also significantly reduced Ba/F3-JAK2 V617F-GFP tumor burden in the JAK2 V617F-induced MPN model with a TED50 of 13.7 mg/kg after oral treatment (BID) for 14 days, indicating that the efficacy of LY2784544 is mediated by pharmacological inhibition of JAK2 V16F-STAT5 pathway. Furthermore, LY2784544 selectively reduced Ba/F3-JAK2 V617F-GFP tumor cells with no effect on CD71/Ter119 positive erythroid progenitors in spleens of SCID mice after oral treatment (BID) for seven days. Conclusions: The in vitro data suggest that constitutively active JAK2 V617F is more sensitive to LY2784544 than cytokine-activated wild type JAK2. Consistent with this observation, in MPN disease model testing, LY2784544 selectively reduces JAK2 V617F tumor cell burden with no effect on erythroid progenitor cells. These findings suggest that as a JAK2 V617F selective targeted therapy, LY2784544 has the potential to induce apoptosis in JAK2 V617F malignant clones while potentially minimizing unintended effects on the normal hematopoietic progenitor cells. These results helped to support the advancement of LY2784544 into an ongoing phase I trial in the MPNs (I3X-MC-JHTA, NCT01134120). Disclosures: Ma: Eli Lilly and Company: Employment. Zhao:Eli Lilly and Company: Employment. Walgren:Eli Lilly and Company: Employment. Clayton:Eli Lilly and Company: Employment. Blosser:Eli Lilly and Company: Employment. Burkholder:Eli Lilly and Company: Employment. Smith:Eli Lilly and Company: Employment.

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