1.
2.
3.
4.
5.
6.
7.
8.
9.
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN
Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249. [CrossRef]
Mattiuzzi, C.; Sanchis-Gomar, F.; Lippi, G. Concise update on colorectal cancer epidemiology. Ann. Transl. Med. 2019, 7, 609.
[CrossRef]
Beppu, T.; Sakamoto, Y.; Hasegawa, K.; Honda, G.; Tanaka, K.; Kotera, Y.; Nitta, H.; Yoshidome, H.; Hatano, E.; Ueno, M.; et al. A
nomogram predicting disease-free survival in patients with colorectal liver metastases treated with hepatic resection: Multicenter
data collection as a Project Study for Hepatic Surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J. Hepatobiliary
Pancreat. Sci. 2012, 19, 72–84. [CrossRef] [PubMed]
Hackl, C.; Gerken, M.; Loss, M.; Klinkhammer-Schalke, M.; Piso, P.; Schlitt, H.J. A population-based analysis on the rate and
surgical management of colorectal liver metastases in Southern Germany. Int. J. Colorectal Dis. 2011, 26, 1475–1481. [CrossRef]
Karnoub, A.E.; Dash, A.B.; Vo, A.P.; Sullivan, A.; Brooks, M.W.; Bell, G.W.; Richardson, A.L.; Polyak, K.; Tubo, R.; Weinberg, R.A.
Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 2007, 449, 557–563. [CrossRef]
Orimo, A.; Gupta, P.B.; Sgroi, D.C.; Arenzana-Seisdedos, F.; Delaunay, T.; Naeem, R.; Carey, V.J.; Richardson, A.L.; Weinberg, R.A.
Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated
SDF-1/CXCL12 secretion. Cell 2005, 121, 335–348. [CrossRef] [PubMed]
Joyce, J.A.; Pollard, J.W. Microenvironmental regulation of metastasis. Nat. Rev. Cancer 2009, 9, 239–252. [CrossRef] [PubMed]
Hinshaw, D.C.; Shevde, L.A. The Tumor Microenvironment Innately Modulates Cancer Progression. Cancer Res. 2019,
79, 4557–4566. [CrossRef]
Peng, Z.; Ye, M.; Ding, H.; Feng, Z.; Hu, K. Spatial transcriptomics atlas reveals the crosstalk between cancer-associated fibroblasts
and tumor microenvironment components in colorectal cancer. J. Transl. Med. 2022, 20, 302. [CrossRef]
Int. J. Mol. Sci. 2023, 24, 1118
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
17 of 19
Mizuno, R.; Kawada, K.; Itatani, Y.; Ogawa, R.; Kiyasu, Y.; Sakai, Y. The Role of Tumor-Associated Neutrophils in Colorectal
Cancer. Int. J. Mol. Sci. 2019, 20, 529. [CrossRef] [PubMed]
Rashtak, S.; Ruan, X.; Druliner, B.R.; Liu, H.; Therneau, T.; Mouchli, M.; Boardman, L.A. Peripheral Neutrophil to Lymphocyte
Ratio Improves Prognostication in Colon Cancer. Clin. Colorectal Cancer 2017, 16, 115–123.e3. [CrossRef] [PubMed]
Borazan, E.; Balik, A.A.; Bozdag, Z.; Arik, M.K.; Aytekin, A.; Yilmaz, L.; Elci, M.; Baskonus, I. Assessment of the relationship
between neutrophil lymphocyte ratio and prognostic factors in non-metastatic colorectal cancer. Turk. J. Surg. 2017, 33, 185–189.
[CrossRef] [PubMed]
Donskov, F. Immunomonitoring and prognostic relevance of neutrophils in clinical trials. Semin. Cancer Biol. 2013, 23, 200–207.
[CrossRef]
Guthrie, G.J.; Charles, K.A.; Roxburgh, C.S.; Horgan, P.G.; McMillan, D.C.; Clarke, S.J. The systemic inflammation-based
neutrophil-lymphocyte ratio: Experience in patients with cancer. Crit. Rev. Oncol. Hematol. 2013, 88, 218–230. [CrossRef]
[PubMed]
Li, Z.; Zhao, R.; Cui, Y.; Zhou, Y.; Wu, X. The dynamic change of neutrophil to lymphocyte ratio can predict clinical outcome in
stage I-III colon cancer. Sci. Rep. 2018, 8, 9453. [CrossRef] [PubMed]
Templeton, A.J.; McNamara, M.G.; Seruga, B.; Vera-Badillo, F.E.; Aneja, P.; Ocana, A.; Leibowitz-Amit, R.; Sonpavde, G.; Knox, J.J.;
Tran, B.; et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: A systematic review and meta-analysis. J. Natl.
Cancer Inst. 2014, 106, dju124. [CrossRef]
Fridlender, Z.G.; Sun, J.; Kim, S.; Kapoor, V.; Cheng, G.; Ling, L.; Worthen, G.S.; Albelda, S.M. Polarization of tumor-associated
neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell 2009, 16, 183–194. [CrossRef]
Wislez, M.; Rabbe, N.; Marchal, J.; Milleron, B.; Crestani, B.; Mayaud, C.; Antoine, M.; Soler, P.; Cadranel, J. Hepatocyte growth
factor production by neutrophils infiltrating bronchioloalveolar subtype pulmonary adenocarcinoma: Role in tumor progression
and death. Cancer Res. 2003, 63, 1405–1412.
Brinkmann, V.; Reichard, U.; Goosmann, C.; Fauler, B.; Uhlemann, Y.; Weiss, D.S.; Weinrauch, Y.; Zychlinsky, A. Neutrophil
extracellular traps kill bacteria. Science 2004, 303, 1532–1535. [CrossRef]
Thomas, M.P.; Whangbo, J.; McCrossan, G.; Deutsch, A.J.; Martinod, K.; Walch, M.; Lieberman, J. Leukocyte protease binding
to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins. J. Immunol. 2014, 192, 5390–5397.
[CrossRef]
Demers, M.; Wagner, D.D. NETosis: A new factor in tumor progression and cancer-associated thrombosis. Semin. Thromb. Hemost.
2014, 40, 277–283. [CrossRef] [PubMed]
Cools-Lartigue, J.; Spicer, J.; McDonald, B.; Gowing, S.; Chow, S.; Giannias, B.; Bourdeau, F.; Kubes, P.; Ferri, L. Neutrophil
extracellular traps sequester circulating tumor cells and promote metastasis. J. Clin. Investig. 2013, 123, 3446–3458. [CrossRef]
[PubMed]
Chen, Q.; Zhang, L.; Li, X.; Zhuo, W. Neutrophil Extracellular Traps in Tumor Metastasis: Pathological Functions and Clinical
Applications. Cancers 2021, 13, 2832. [CrossRef] [PubMed]
Roskoski, R., Jr. ERK1/2 MAP kinases: Structure, function, and regulation. Pharmacol. Res. 2012, 66, 105–143. [CrossRef]
Kajioka, H.; Kagawa, S.; Ito, A.; Yoshimoto, M.; Sakamoto, S.; Kikuchi, S.; Kuroda, S.; Yoshida, R.; Umeda, Y.; Noma, K.; et al.
Targeting neutrophil extracellular traps with thrombomodulin prevents pancreatic cancer metastasis. Cancer Lett. 2021, 497, 1–13.
[CrossRef]
Najmeh, S.; Cools-Lartigue, J.; Rayes, R.F.; Gowing, S.; Vourtzoumis, P.; Bourdeau, F.; Giannias, B.; Berube, J.; Rousseau, S.; Ferri,
L.E.; et al. Neutrophil extracellular traps sequester circulating tumor cells via beta1-integrin mediated interactions. Int. J. Cancer
2017, 140, 2321–2330. [CrossRef]
Tohme, S.; Yazdani, H.O.; Al-Khafaji, A.B.; Chidi, A.P.; Loughran, P.; Mowen, K.; Wang, Y.; Simmons, R.L.; Huang, H.; Tsung, A.
Neutrophil Extracellular Traps Promote the Development and Progression of Liver Metastases after Surgical Stress. Cancer Res.
2016, 76, 1367–1380. [CrossRef]
Takesue, S.; Ohuchida, K.; Shinkawa, T.; Otsubo, Y.; Matsumoto, S.; Sagara, A.; Yonenaga, A.; Ando, Y.; Kibe, S.;
Nakayama, H.; et al. Neutrophil extracellular traps promote liver micrometastasis in pancreatic ductal adenocarcinoma
via the activation of cancerassociated fibroblasts. Int. J. Oncol. 2020, 56, 596–605. [CrossRef] [PubMed]
Demkow, U. Neutrophil Extracellular Traps (NETs) in Cancer Invasion, Evasion and Metastasis. Cancers 2021, 13, 4495. [CrossRef]
[PubMed]
Najmeh, S.; Cools-Lartigue, J.; Giannias, B.; Spicer, J.; Ferri, L.E. Simplified Human Neutrophil Extracellular Traps (NETs) Isolation
and Handling. J. Vis. Exp. 2015, 98, e52687. [CrossRef]
Köckritz-Blickwede, M.v.; Chow, O.A.; Nizet, V. Fetal calf serum contains heat-stable nucleases that degrade neutrophil extracellular traps. Blood 2009, 114, 5245–5246. [CrossRef] [PubMed]
von Köckritz-Blickwede, M.; Chow, O.; Ghochani, M.; Nizet, V. Visualization and Functional Evaluation of Phagocyte Extracellular
Traps. In Immunology of Infection; Academic Press: Cambridge, MA, USA, 2010; Volume 37, pp. 139–160. [CrossRef]
Papayannopoulos, V.; Metzler, K.D.; Hakkim, A.; Zychlinsky, A. Neutrophil elastase and myeloperoxidase regulate the formation
of neutrophil extracellular traps. J. Cell Biol. 2010, 191, 677–691. [CrossRef] [PubMed]
Int. J. Mol. Sci. 2023, 24, 1118
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
18 of 19
Sebolt-Leopold, J.S.; Dudley, D.T.; Herrera, R.; Van Becelaere, K.; Wiland, A.; Gowan, R.C.; Tecle, H.; Barrett, S.D.; Bridges, A.;
Przybranowski, S.; et al. Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nat. Med. 1999,
5, 810–816. [CrossRef] [PubMed]
Fang, J.Y.; Richardson, B.C. The MAPK signalling pathways and colorectal cancer. Lancet Oncol. 2005, 6, 322–327. [CrossRef]
[PubMed]
Palamidessi, A.; Malinverno, C.; Frittoli, E.; Corallino, S.; Barbieri, E.; Sigismund, S.; Beznoussenko, G.V.; Martini, E.; Garre, M.;
Ferrara, I.; et al. Unjamming overcomes kinetic and proliferation arrest in terminally differentiated cells and promotes collective
motility of carcinoma. Nat. Mater. 2019, 18, 1252–1263. [CrossRef]
Tanaka, S.; Takizawa, K.; Nakamura, F. One-step visualization of natural cell activities in non-labeled living spheroids. Sci. Rep.
2022, 12, 1500. [CrossRef]
Itatani, Y.; Kawada, K.; Fujishita, T.; Kakizaki, F.; Hirai, H.; Matsumoto, T.; Iwamoto, M.; Inamoto, S.; Hatano, E.;
Hasegawa, S.; et al. Loss of SMAD4 from colorectal cancer cells promotes CCL15 expression to recruit CCR1+ myeloid
cells and facilitate liver metastasis. Gastroenterology 2013, 145, 1064–1075.e11. [CrossRef]
Metzler, K.D.; Goosmann, C.; Lubojemska, A.; Zychlinsky, A.; Papayannopoulos, V. A myeloperoxidase-containing complex
regulates neutrophil elastase release and actin dynamics during NETosis. Cell Rep. 2014, 8, 883–896. [CrossRef]
Vorobjeva, N.V.; Chernyak, B.V. NETosis: Molecular Mechanisms, Role in Physiology and Pathology. Biochemistry 2020,
85, 1178–1190. [CrossRef]
Teijeira, A.; Garasa, S.; Gato, M.; Alfaro, C.; Migueliz, I.; Cirella, A.; de Andrea, C.; Ochoa, M.C.; Otano, I.; Etxeberria, I.; et al.
CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere
with Immune Cytotoxicity. Immunity 2020, 52, 856–871.e8. [CrossRef]
Zhu, Y.; Huang, Y.; Ji, Q.; Fu, S.; Gu, J.; Tai, N.; Wang, X. Interplay between Extracellular Matrix and Neutrophils in Diseases. J.
Immunol. Res. 2021, 2021, 8243378. [CrossRef] [PubMed]
Albrengues, J.; Shields, M.A.; Ng, D.; Park, C.G.; Ambrico, A.; Poindexter, M.E.; Upadhyay, P.; Uyeminami, D.L.; Pommier, A.;
Kuttner, V.; et al. Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science
2018, 361, 4227. [CrossRef] [PubMed]
Thalin, C.; Hisada, Y.; Lundstrom, S.; Mackman, N.; Wallen, H. Neutrophil Extracellular Traps: Villains and Targets in Arterial,
Venous, and Cancer-Associated Thrombosis. Arterioscler. Thromb. Vasc. Biol. 2019, 39, 1724–1738. [CrossRef] [PubMed]
Zhang, H.; Lv, H.; Weng, M.; Wang, H.; Cata, J.P.; Chen, W.; Miao, C. Preoperative leukocytosis is associated with increased
tumor-infiltrating neutrophil extracellular traps and worse outcomes in esophageal cancer. Ann. Transl. Med. 2020, 8, 441.
[CrossRef]
Rayes, R.F.; Mouhanna, J.G.; Nicolau, I.; Bourdeau, F.; Giannias, B.; Rousseau, S.; Quail, D.; Walsh, L.; Sangwan, V.; Bertos,
N.; et al. Primary tumors induce neutrophil extracellular traps with targetable metastasis promoting effects. JCI Insight 2019,
5, e128008. [CrossRef]
Zhang, Y.; Hu, Y.; Ma, C.; Sun, H.; Wei, X.; Li, M.; Wei, W.; Zhang, F.; Yang, F.; Wang, H.; et al. Diagnostic, Therapeutic Predictive,
and Prognostic Value of Neutrophil Extracellular Traps in Patients With Gastric Adenocarcinoma. Front. Oncol. 2020, 10, 1036.
[CrossRef]
Yazdani, H.O.; Roy, E.; Comerci, A.J.; van der Windt, D.J.; Zhang, H.; Huang, H.; Loughran, P.; Shiva, S.; Geller, D.A.; Bartlett,
D.L.; et al. Neutrophil Extracellular Traps Drive Mitochondrial Homeostasis in Tumors to Augment Growth. Cancer Res. 2019,
79, 5626–5639. [CrossRef]
Lerman, I.; Hammes, S.R. Neutrophil elastase in the tumor microenvironment. Steroids 2018, 133, 96–101. [CrossRef]
Vaguliene, N.; Zemaitis, M.; Lavinskiene, S.; Miliauskas, S.; Sakalauskas, R. Local and systemic neutrophilic inflammation in
patients with lung cancer and chronic obstructive pulmonary disease. BMC Immunol. 2013, 14, 36. [CrossRef]
Kistowski, M.; Debski, J.; Karczmarski, J.; Paziewska, A.; Oledzki, J.; Mikula, M.; Ostrowski, J.; Dadlez, M. A Strong Neutrophil
Elastase Proteolytic Fingerprint Marks the Carcinoma Tumor Proteome. Mol. Cell. Proteom. 2017, 16, 213–227. [CrossRef]
Akizuki, M.; Fukutomi, T.; Takasugi, M.; Takahashi, S.; Sato, T.; Harao, M.; Mizumoto, T.; Yamashita, J.-I. Prognostic Significance
of Immunoreactive Neutrophil Elastase in Human Breast Cancer: Long-Term Follow-Up Results in 313 Patients. Neoplasia 2007,
9, 260–264. [CrossRef]
Foekens, J.A.; Ries, C.; Look, M.P.; Gippner-Steppert, C.; Klijn, J.G.; Jochum, M. Elevated expression of polymorphonuclear
leukocyte elastase in breast cancer tissue is associated with tamoxifen failure in patients with advanced disease. Br. J. Cancer 2003,
88, 1084–1090. [CrossRef] [PubMed]
Foekens, J.A.; Ries, C.; Look, M.P.; Gippner-Steppert, C.; Klijn, J.G.; Jochum, M. The prognostic value of polymorphonuclear
leukocyte elastase in patients with primary breast cancer. Cancer Res. 2003, 63, 337–341. [PubMed]
Chiossone, L.; Dumas, P.Y.; Vienne, M.; Vivier, E. Natural killer cells and other innate lymphoid cells in cancer. Nat. Rev. Immunol.
2018, 18, 671–688. [CrossRef] [PubMed]
Lavoie, H.; Gagnon, J.; Therrien, M. ERK signalling: A master regulator of cell behaviour, life and fate. Nat. Rev. Mol. Cell Biol.
2020, 21, 607–632. [CrossRef] [PubMed]
Kohri, K.; Ueki, I.F.; Nadel, J.A. Neutrophil elastase induces mucin production by ligand-dependent epidermal growth factor
receptor activation. Am. J. Physiol. Lung Cell. Mol. Physiol. 2002, 283, L531–L540. [CrossRef]
Int. J. Mol. Sci. 2023, 24, 1118
58.
59.
60.
61.
62.
63.
64.
65.
66.
67.
68.
69.
70.
71.
72.
73.
74.
75.
76.
77.
78.
79.
80.
19 of 19
Grosse-Steffen, T.; Giese, T.; Giese, N.; Longerich, T.; Schirmacher, P.; Hansch, G.M.; Gaida, M.M. Epithelial-to-mesenchymal
transition in pancreatic ductal adenocarcinoma and pancreatic tumor cell lines: The role of neutrophils and neutrophil-derived
elastase. Clin. Dev. Immunol. 2012, 2012, 720768. [CrossRef]
Topic, A.; Ljujic, M.; Nikolic, A.; Petrovic-Stanojevic, N.; Dopudja-Pantic, V.; Mitic-Milikic, M.; Radojkovic, D. Alpha-1-antitrypsin
phenotypes and neutrophil elastase gene promoter polymorphisms in lung cancer. Pathol. Oncol. Res. 2011, 17, 75–80. [CrossRef]
Yang, L.; Liu, Q.; Zhang, X.; Liu, X.; Zhou, B.; Chen, J.; Huang, D.; Li, J.; Li, H.; Chen, F.; et al. DNA of neutrophil extracellular
traps promotes cancer metastasis via CCDC25. Nature 2020, 583, 133–138. [CrossRef]
Deryugina, E.; Carre, A.; Ardi, V.; Muramatsu, T.; Schmidt, J.; Pham, C.; Quigley, J.P. Neutrophil Elastase Facilitates Tumor Cell
Intravasation and Early Metastatic Events. iScience 2020, 23, 101799. [CrossRef]
Lee, W.; Ko, S.Y.; Mohamed, M.S.; Kenny, H.A.; Lengyel, E.; Naora, H. Neutrophils facilitate ovarian cancer premetastatic niche
formation in the omentum. J. Exp. Med. 2019, 216, 176–194. [CrossRef] [PubMed]
Zha, C.; Meng, X.; Li, L.; Mi, S.; Qian, D.; Li, Z.; Wu, P.; Hu, S.; Zhao, S.; Cai, J.; et al. Neutrophil extracellular traps mediate the
crosstalk between glioma progression and the tumor microenvironment via the HMGB1/RAGE/IL-8 axis. Cancer Biol. Med. 2020,
17, 154–168. [CrossRef] [PubMed]
Ma, P.P.; Zhu, D.; Liu, B.Z.; Zhong, L.; Zhu, X.Y.; Wang, H.; Zhang, X.; Gao, Y.M.; Hu, X.X. Neutrophil elastase inhibitor on
proliferation and apoptosis of U937 cells. Zhonghua Xue Ye Xue Za Zhi 2013, 34, 507–511. [CrossRef]
Nawa, M.; Osada, S.; Morimitsu, K.; Nonaka, K.; Futamura, M.; Kawaguchi, Y.; Yoshida, K. Growth effect of neutrophil elastase
on breast cancer: Favorable action of sivelestat and application to anti-HER2 therapy. Anticancer Res. 2012, 32, 13–19.
Park, J.; Wysocki, R.W.; Amoozgar, Z.; Maiorino, L.; Fein, M.R.; Jorns, J.; Schott, A.F.; Kinugasa-Katayama, Y.; Lee, Y.; Won,
N.H.; et al. Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps. Sci. Transl. Med. 2016, 8, 361ra138.
[CrossRef]
Xiao, Y.; Cong, M.; Li, J.; He, D.; Wu, Q.; Tian, P.; Wang, Y.; Yang, S.; Liang, C.; Liang, Y.; et al. Cathepsin C promotes breast
cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation. Cancer Cell 2021, 39,
423–437.e427. [CrossRef] [PubMed]
Pu, S.; Wang, D.; Liu, D.; Zhao, Y.; Qi, D.; He, J.; Zhou, G. Effect of sivelestat sodium in patients with acute lung injury or acute
respiratory distress syndrome: A meta-analysis of randomized controlled trials. BMC Pulm. Med. 2017, 17, 148. [CrossRef]
Kessenbrock, K.; Krumbholz, M.; Schonermarck, U.; Back, W.; Gross, W.L.; Werb, Z.; Grone, H.J.; Brinkmann, V.; Jenne, D.E.
Netting neutrophils in autoimmune small-vessel vasculitis. Nat. Med. 2009, 15, 623–625. [CrossRef]
Nie, M.; Yang, L.; Bi, X.; Wang, Y.; Sun, P.; Yang, H.; Liu, P.; Li, Z.; Xia, Y.; Jiang, W. Neutrophil Extracellular Traps Induced by IL8
Promote Diffuse Large B-cell Lymphoma Progression via the TLR9 Signaling. Clin. Cancer Res. 2019, 25, 1867–1879. [CrossRef]
Ogawa, R.; Yamamoto, T.; Hirai, H.; Hanada, K.; Kiyasu, Y.; Nishikawa, G.; Mizuno, R.; Inamoto, S.; Itatani, Y.; Sakai, Y.; et al.
Loss of SMAD4 Promotes Colorectal Cancer Progression by Recruiting Tumor-Associated Neutrophils via the CXCL1/8-CXCR2
Axis. Clin. Cancer Res. 2019, 25, 2887–2899. [CrossRef]
Hanada, K.; Kawada, K.; Nishikawa, G.; Toda, K.; Maekawa, H.; Nishikawa, Y.; Masui, H.; Hirata, W.; Okamoto, M.;
Kiyasu, Y.; et al. Dual blockade of macropinocytosis and asparagine bioavailability shows synergistic anti-tumor effects
on KRAS-mutant colorectal cancer. Cancer Lett. 2021, 522, 129–141. [CrossRef]
Nishikawa, G.; Kawada, K.; Nakagawa, J.; Toda, K.; Ogawa, R.; Inamoto, S.; Mizuno, R.; Itatani, Y.; Sakai, Y. Bone marrow-derived
mesenchymal stem cells promote colorectal cancer progression via CCR5. Cell Death Dis. 2019, 10, 264. [CrossRef] [PubMed]
Wada, Y.; Yoshida, K.; Hihara, J.; Konishi, K.; Tanabe, K.; Ukon, K.; Taomoto, J.; Suzuki, T.; Mizuiri, H. Sivelestat, a specific
neutrophil elastase inhibitor, suppresses the growth of gastric carcinoma cells by preventing the release of transforming growth
factor-alpha. Cancer Sci. 2006, 97, 1037–1043. [CrossRef] [PubMed]
Taya, M.; Garcia-Hernandez, M.L.; Rangel-Moreno, J.; Minor, B.; Gibbons, E.; Hammes, S.R. Neutrophil elastase from myeloid
cells promotes TSC2-null tumor growth. Endocr. Relat. Cancer 2020, 27, 261–274. [CrossRef] [PubMed]
Okeke, E.B.; Louttit, C.; Fry, C.; Najafabadi, A.H.; Han, K.; Nemzek, J.; Moon, J.J. Inhibition of neutrophil elastase prevents
neutrophil extracellular trap formation and rescues mice from endotoxic shock. Biomaterials 2020, 238, 119836. [CrossRef]
[PubMed]
Komatsu, N.; Aoki, K.; Yamada, M.; Yukinaga, H.; Fujita, Y.; Kamioka, Y.; Matsuda, M. Development of an optimized backbone of
FRET biosensors for kinases and GTPases. Mol. Biol. Cell 2011, 22, 4647–4656. [CrossRef]
Aoki, K.; Matsuda, M. Visualization of small GTPase activity with fluorescence resonance energy transfer-based biosensors. Nat.
Protoc. 2009, 4, 1623–1631. [CrossRef]
Mizuno, R.; Kamioka, Y.; Kabashima, K.; Imajo, M.; Sumiyama, K.; Nakasho, E.; Ito, T.; Hamazaki, Y.; Okuchi, Y.; Sakai, Y.; et al.
In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines. J. Exp. Med. 2014,
211, 1123–1136. [CrossRef]
Yuan, Q.; Jiang, Y.W.; Fang, Q.H. Improving effect of Sivelestat on lipopolysaccharide-induced lung injury in rats. APMIS 2014,
122, 810–817. [CrossRef]
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