Targeting Mast Cells Tryptase in Tumor Microenvironment: A Potential Antiangiogenetic Strategy

Table 2

All studies mentioned above that have considered nafamostat mesylate.

Author, reference, year	Drug/s	Tumor target	Molecular mechanisms of action	Results
Jikuhara et al. [49] 2003	nafamostat mesylate	human colon cancer cell line (DLD-1)	(1) inhibition of PAR-2 stimulation via MAPK- and COX-dependent manner; (2) inhibition of VEGF and FGF-2 levels	inhibition of tumor cell growth, angiogenesis, invasion, metastasis
Yoshii et al. [50] 2005	nafamostat mesylate	human colon cancer cell line (DLD-1)	(1) Inhibition of PAR-2 stimulation via MAPK- and COX-dependent manner; (2) Inhibition of the release of IL-6 and GM-CSF	inhibition of angiogenesis, cell growth, invasion, metastasis
Tajima et al. [51] 2001	nafamostat mesylate	several human pancreatic cancer cell lines	antagonizing TAT-induced activation of PAR-2	inhibition of tumor cell growth and invasion
Ohta et al. [52] 2003	nafamostat mesylate	several human pancreatic cancer cell lines	antagonizing TAT-induced activation of PAR-2	inhibition of tumor cell growth and invasion
Uwagawa et al. [53] 2009	(1) nafamostat mesylate; (2) nafamostat mesylate plus gemcitabine	human pancreatic cancer cell line (Panc-1)	Down-regulation of NF-κB with reduction of ICAM-1, IL-8, VEGF, MMP-9, uPA, RRM1	(1) inhibition of tumor cell adhesion and growth, angiogenesis, invasion metastasis; (2) increase of apoptosis; (3) increase of body weight loss of mice
Uwagawa et al. [54] 2009	nafamostat mesylate plus intra-arterial gemcitabine	unresectable locally advanced or metastatic pancreatic cancer; (20 pts)	not analyzed	(1) CBR of 60%; (2) reduction of CA19-9 serum level in 90% of pts; (3) improvement in health-related quality of life
Fujiwara et al. [55] 2011	nafamostat mesylate	human pancreatic cancer cell lines; (AsPC-1, BxPC-3, PANC-1)	down-regulation of IkBα, NF-κB with reduction of ICAM-1, IL-8, VEGF, MMP-9, uPA	(1) increase of cell adhesion, programmed cell death; (2) inhibition of angiogenesis, invasion, metastasis in peritoneal dissemination
Gocho et al. [56] 2013	(1) nafamostat mesylate; (2) nafamostat mesylate; plus oxaliplatin	human pancreatic cancer cell line; (Panc-1) and pancreatic cancer mouse model	down-regulation of NF-κB with reduction of ICAM-1, IL-8, VEGF, MMP-9, uPA, c-IAP1, c-IAP2	(1) increase of cell adhesion, caspase-8-mediated apoptosis; (2) inhibition of PARP, angiogenesis, invasion and metastasis,; (3) synergistic cytotoxic effect

PAR-2, Protease-activated receptor-2; MAPK, mitogen-activated protein kinase; COX, cyclooxygenase; IL, Interleukin; GM-CSF, Granulocyte-macrophage colony stimulating factor; TAT, Tumor-associated trypsinogen; IkB, Inhibitor of NF-κB; NF-κB, Nuclear factor-kappaB; MMPs, metalloproteinases; uPA, urokinase-type plasminogen activator; ICAM-1, Intercellular Adhesion Molecule-1, VEGF, Vascular endothelial growth factor, IAP, Inhibitors of apoptosis.