scholarly journals Anti-metastatic effect of the TM4SF5-specific peptide vaccine and humanized monoclonal antibody on colon cancer in a mouse lung metastasis model

Oncotarget ◽  
2016 ◽  
Vol 7 (48) ◽  
pp. 79170-79186 ◽  
Author(s):  
Guang Wu ◽  
Dongbum Kim ◽  
Byoung Kwon Park ◽  
Sangkyu Park ◽  
Ji-Hee Ha ◽  
...  
2009 ◽  
Vol 96 (5) ◽  
pp. 550-557 ◽  
Author(s):  
Lawrence T. Dauer ◽  
Daniel C. Boylan ◽  
Matthew J. Williamson ◽  
Jean St. Germain ◽  
Steven M. Larson

2016 ◽  
Vol 16 (4) ◽  
pp. 585-596 ◽  
Author(s):  
Ji-Ye Kee ◽  
Yo-Han Han ◽  
Jinbong Park ◽  
Dae-Seung Kim ◽  
Jeong-Geon Mun ◽  
...  

Background: β-Lapachone is a quinone-containing compound found in red lapacho ( Tabebuia impetiginosa, syn. T avellanedae) trees. Lapacho has been used in traditional medicine by several South and Central American indigenous people to treat various types of cancer. The purpose of this study was to investigate the antimetastatic properties of β-lapachone and the underlying mechanisms using colon cancer cells. Methods: This research used metastatic murine colon cancer cell lines, colon 26 (CT26) and colon 38 (MC38). A WST assay, annexin V assay, cell cycle analysis, wound healing assay, invasion assay, western blot analysis, and real-time reverse transcription–polymerase chain reaction were performed to examine the effects of β-lapachone on metastatic phenotypes and molecular mechanisms. The effect of β-lapachone on lung metastasis was assessed in a mouse experimental metastasis model. Results: We found that the inhibition of proliferation of the colon cancer cell lines by β-lapachone was due to the induction of apoptosis and cell cycle arrest. β-Lapachone induced the apoptosis of CT26 cells through caspase-3, -8, and -9 activation; poly(ADP-ribose) polymerase cleavage; and downregulation of the Bcl-2 family in a dose- and time-dependent manner. In addition, a low concentration of β-lapachone decreased the cell migration and invasion by decreasing the expression of matrix metalloproteinases-2 and -9, and increased the expression of tissue inhibitors of metalloproteinases-1 and -2. Moreover, β-lapachone treatment regulated the expression of epithelial-mesenchymal transition markers such as E- and N-cadherin, vimentin, β-catenin, and Snail in CT26 cells. In the mouse experimental metastasis model, β-lapachone significantly inhibited the lung metastasis of CT26 cells. Conclusions: Our results demonstrated the inhibitory effect of β-lapachone on colorectal lung metastasis. This compound may be useful for developing therapeutic agents to treat metastatic cancer.


2010 ◽  
Vol 78 (1) ◽  
pp. 7
Author(s):  
Jong Man Kim ◽  
Sung Joo Kim ◽  
Jae-Won Joh ◽  
Choon Hyuck David Kwon ◽  
Haejung Park ◽  
...  

1995 ◽  
Vol 35 (6) ◽  
pp. 447-456
Author(s):  
Atsuhide Mori ◽  
Stephen J. Kennel ◽  
Marjan Borssum Waalkes ◽  
Gerrit L. Scherphof ◽  
L. Huang

2014 ◽  
Author(s):  
George E. Sandusky ◽  
Ronne Surface ◽  
Eva Tonsing-Carter ◽  
jayne Silver ◽  
Tony Sinn ◽  
...  

Author(s):  
R.F Meredith ◽  
A Forero ◽  
M Khazaeli ◽  
M Carpenter ◽  
J Schlom ◽  
...  

1995 ◽  
Vol 35 (6) ◽  
pp. 447-456 ◽  
Author(s):  
Atsuhide Mori ◽  
Stephen J. Kennel ◽  
Marjan van Borssum Waalkes ◽  
Gerrit L. Scherphof ◽  
Leaf Huang

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Xuanmao Jiao ◽  
Min Wang ◽  
Zhao Zhang ◽  
Zhiping Li ◽  
Dong Ni ◽  
...  

Abstract Background Triple-negative breast cancer (BCa) (TNBC) is a deadly form of human BCa with limited treatment options and poor prognosis. In our prior analysis of over 2200 breast cancer samples, the G protein-coupled receptor CCR5 was expressed in > 95% of TNBC samples. A humanized monoclonal antibody to CCR5 (leronlimab), used in the treatment of HIV-infected patients, has shown minimal side effects in large patient populations. Methods A humanized monoclonal antibody to CCR5, leronlimab, was used for the first time in tissue culture and in mice to determine binding characteristics to human breast cancer cells, intracellular signaling, and impact on (i) metastasis prevention and (ii) impact on established metastasis. Results Herein, leronlimab was shown to bind CCR5 in multiple breast cancer cell lines. Binding of leronlimab to CCR5 reduced ligand-induced Ca+ 2 signaling, invasion of TNBC into Matrigel, and transwell migration. Leronlimab enhanced the BCa cell killing of the BCa chemotherapy reagent, doxorubicin. In xenografts conducted with Nu/Nu mice, leronlimab reduced lung metastasis of the TNBC cell line, MB-MDA-231, by > 98% at 6 weeks. Treatment with leronlimab reduced the metastatic tumor burden of established TNBC lung metastasis. Conclusions The safety profile of leronlimab, together with strong preclinical evidence to both prevent and reduce established breast cancer metastasis herein, suggests studies of clinical efficacy may be warranted.


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