scholarly journals Comparison of the cytotoxic effects of single and divided treatment of 4-hydroxycyclophosphamide at the same total dosage amount in canine lymphoma cell lines

2020 ◽  
Vol 65 (No. 2) ◽  
pp. 56-61
Author(s):  
AT Liao ◽  
YC Chen ◽  
SL Wang

Cyclophosphamide is widely used in combination chemotherapy to treat dogs with lymphoma. The metabolite of cyclophosphamide, acrolein, can irritate the urinary bladder and cause sterile haemorrhagic cystitis. The divided administration of cyclophosphamide across multiple days may reduce the occurrence of the cystitis. However, the therapeutic effect of this modification has not been evaluated and compared to the traditional single maximum-tolerated dose. It is difficult to evaluate the cytotoxic effect by the single chemotherapeutic drug in dogs. In order to verify the effect of the single and divided treatment of cyclophosphamide in canine lymphoma, we used two canine lymphoma cell lines (CLBL-1, B-cell lymphoma and UL-1, T-cell lymphoma) to imitate the clinical conditions. The cell viability in the CLBL-1 and UL-1 cells treated by a single dosage of 4-hydroxycyclophosphamide after 48 h were 70.4% and 61.5%, respectively. The cell viability in the CLBL-1 and UL-1 cells treated by the divided dosage of 4-hydroxycyclophosphamide after 48 h were 109.4% and 50.8%. There were no significant differences between the two administration methods in the T-cell lymphoma cell line (P = 0.215). The single full dosage of 4-hydroxycyclophosphamide exhibited a significant cytotoxic effect rather than the divided dosage in B-cell lymphoma cell line (P = 0.007) did. The maximum-tolerated dose of cyclophosphamide is still recommended to be used in dogs with B-cell lymphoma.

Gene ◽  
2000 ◽  
Vol 251 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Koichi Ichimura ◽  
Hiroko Hanafusa ◽  
Hidetaka Takimoto ◽  
Yoichiro Ohgama ◽  
Tadaatsu Akagi ◽  
...  

1997 ◽  
Vol 12 (3) ◽  
pp. 177-186 ◽  
Author(s):  
Aicha Demidem ◽  
Tammy Lam ◽  
Steve Alas ◽  
Kandasamy Hariharan ◽  
Nabil Hanna ◽  
...  

2020 ◽  
Vol 390 (2) ◽  
pp. 111986
Author(s):  
Michael C. Rahe ◽  
Cheryl M.T. Dvorak ◽  
Barry Wiseman ◽  
Daniel Martin ◽  
Michael P. Murtaugh

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4912-4912
Author(s):  
Kazumi Hagiwara ◽  
Yuki Kojima ◽  
Yasuhiko Miyata ◽  
Hirokazu Nagai

Abstract Abstract 4912 Bendamustine, a kind of alkylating agent, has demonstrated a favorable anti-tumor activity both alone and in combination with rituximab in low grade B cell lymphoma. Because the kinase cascades, including B-cell receptor signaling, are necessary for the proliferation and survival of the lymphoma cells, the kinase inhibitors have been developed as molecular target agents of malignant lymphomas. We investigated the cytotoxic effect of bendamustine, both as a single agent and in combination with these new kinase inhibitors in human lymphoid cell lines. We used three B-cell lines, BALL-1 (acute lymphoblastic leukemia), SKLY16 (B-cell lymphoma) and DHL4 (diffuse large B cell lymphoma), and T-cell line THP-6 in this study. These cells were treated with bendamustine alone or combined with enzastaurin (a PKC-β inhibitor), CAL-101 (a p110δ PI3K inhibitor), PCI-32765 (a Btk inhibitor) or R406 (a Syk inhibitor) for 48 hours. Drug-induced cytotoxicity was evaluated using the MTT assay. Cell viability in each experiment was normalized using untreated controls. The treatment with bendamustine alone decreased cell viability in a dose-dependent manner on these three B-cell lines. In contrast, T-cell line THP-6 showed the resistance to bendamusitine. For the combination study, cells were exposed to bendamustine (10μM) and one of these kinase inhibitors at various concentrations simultaneously for 48 hours. CAL-101 and PCI-32765 did not enhance the cytotoxic effect on all of B-cell lines. In BALL-1 and SKLY16 cells, the combination with enzastaurin or R406 resulted in a higher cytotoxic activity than that induced by bendamustine alone. In DHL4 cells, the treatment combined with R406 inhibited cell growth effectively, but not with enzastaurin. To evaluate whether these drug combinations are synergistic, a combination index (CI) was calculated and normalized isobolograms were constructed from non-constant ratio drug combinations using Calcusyn software. The CI values were less than 0. 7 in SKLY16 cells treated with bendamustine and enzastaurin, indicating that these produced synergistic cytotoxic effects in cell line-dependent manner. Our results show that enzastaurin might potentiate the cytotoxic activity of bendamustine in vitro and be a good candidate for the combination with bendamustine. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2004 ◽  
Vol 104 (3) ◽  
pp. 815-821 ◽  
Author(s):  
Li Li ◽  
Sun-Ok Yoon ◽  
Dan-Dan Fu ◽  
Xin Zhang ◽  
Yong Sung Choi

Abstract The lymphoid follicle is a specialized microenvironment for the differentiation of antigen (Ag)–activated B cells; the major stromal cell components in lymphoid follicle are the follicular dendritic cells (FDCs). At the same time, most of the B-cell lymphomas originate from the germinal center, and the generation and blast transformation of B-cell lymphoma occurs in close association with FDCs in the early stage of tumorigenesis. To study the functional roles of FDCs in lymphomagenesis, we established an inducible tumor model. The human B-cell lymphoma cell line, L3055, formed solid tumors only when inoculated with an FDC line, HK. In addition, 2 FDC-signaling molecules (FDC-SMs), a novel protein 8D6 and 4G10/CD44, are required for tumor formation in vivo, because monoclonal antibodies (mAbs) specific to these 2 proteins inhibited lymphomagenesis completely when they were inoculated with L3055 and HK cells. However, these 2 FDC-SMs have distinct functional roles in tumor formation. FDC-SM-8D6 enhances L3055 cell proliferation, whereas FDC-SM-4G10/CD44 inhibits its apoptosis. Identification of the functional roles of these critical FDC-SMs may lead to the discovery of therapeutic drugs that suppress the survival and growth of lymphoma cells.


Oncotarget ◽  
2017 ◽  
Vol 8 (70) ◽  
pp. 114924-114934 ◽  
Author(s):  
Reem Karmali ◽  
Vineela Chukkapalli ◽  
Leo I. Gordon ◽  
Jeffrey A. Borgia ◽  
Andrey Ugolkov ◽  
...  

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