Inhibition of LPS-mediated TLR4 activation abrogates gastric adenocarcinoma-associated peritoneal metastasis.
Ex vivo
Gram negative bacteria
Lipopolysaccharide
Peritoneal metastasis assay
Journal
Clinical & experimental metastasis
ISSN: 1573-7276
Titre abrégé: Clin Exp Metastasis
Pays: Netherlands
ID NLM: 8409970
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
11
02
2021
accepted:
06
11
2021
pubmed:
13
11
2021
medline:
5
4
2022
entrez:
12
11
2021
Statut:
ppublish
Résumé
Surgical resection, the cornerstone of curative intent treatment for gastric adenocarcinoma, is associated with a high rate of infection-related post-operative complications, leading to an increased incidence of metastasis to the peritoneum. However, the mechanisms underlying this process are poorly understood. Lipopolysaccharide (LPS), an antigen from Gram-negative bacteria, represents a potential mechanism via induction of local and systemic inflammation through activation of Toll-like receptor (TLR). Here, we use both a novel ex vivo model of peritoneal metastasis and in vivo animal models to assess gastric cancer cell adhesion to peritoneum both before and after inhibition of the TLR4 pathway. We demonstrate that activation of TLR4 by either LPS or Gram-negative bacteria (E. coli) significantly increases the adherence of gastric cancer cells to human peritoneal mesothelial cells, and that this increased adherence is abrogated by inhibition of the TLR4 signal cascade and downstream TAK1 and MEK1/2 pathways. We also demonstrate that the influence of LPS on adherence extends to peritoneal tissue and metastatic spread. Furthermore, we show that loss of TLR4 at the site of metastasis reduces tumor cell adhesion, implicating the TLR4 signaling cascade in potentiating metastatic adhesion and peritoneal spread. These results identify potential therapeutic targets for the clinical management of patients undergoing resection for gastric cancer.
Identifiants
pubmed: 34767138
doi: 10.1007/s10585-021-10133-8
pii: 10.1007/s10585-021-10133-8
doi:
Substances chimiques
Lipopolysaccharides
0
TLR4 protein, human
0
Toll-Like Receptor 4
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
323-333Subventions
Organisme : CIHR
Pays : Canada
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Castano-Rodriguez N, Kaakoush NO, Mitchell HM (2014) Pattern-recognition receptors and gastric cancer. Front Immunol 5:336. doi: https://doi.org/10.3389/fimmu.2014.00336
doi: 10.3389/fimmu.2014.00336
pubmed: 25101079
pmcid: 4105827
Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66(1):7–30. doi: https://doi.org/10.3322/caac.21332
doi: 10.3322/caac.21332
pubmed: 26742998
Zhang XF, Huang CM, Lu HS, Wu XY, Wang C, Guang GX, Zhang JZ, Zheng CH (2004) Surgical treatment and prognosis of gastric cancer in 2,613 patients. World J Gastroenterol 10(23):3405–3408. doi: https://doi.org/10.3748/wjg.v10.i23.3405
doi: 10.3748/wjg.v10.i23.3405
pubmed: 15526356
pmcid: 4576218
Deng J, Liang H, Wang D, Sun D, Pan Y, Liu Y (2011) Investigation of the recurrence patterns of gastric cancer following a curative resection. Surg Today 41(2):210–215. doi: https://doi.org/10.1007/s00595-009-4251-y
doi: 10.1007/s00595-009-4251-y
pubmed: 21264756
Riihimaki M, Hemminki A, Sundquist K, Sundquist J, Hemminki K (2016) Metastatic spread in patients with gastric cancer. Oncotarget 7(32):52307–52316. doi: https://doi.org/10.18632/oncotarget.10740
doi: 10.18632/oncotarget.10740
pubmed: 27447571
pmcid: 5239553
Arslan NC, Sokmen S, Avkan-Oguz V, Obuz F, Canda AE, Terzi C, Fuzun M (2017) Infectious complications after cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy. Surg Infect (Larchmt) 18(2):157–163. https://doi.org/10.1089/sur.2016.102
doi: 10.1089/sur.2016.102
Xiao H, Xiao Y, Quan H, Liu W, Pan S, Ouyang Y (2017) Intra-abdominal infection after radical gastrectomy for gastric cancer: Incidence, pathogens, risk factors and outcomes. Int J Surg 48:195–200. doi: https://doi.org/10.1016/j.ijsu.2017.07.081
doi: 10.1016/j.ijsu.2017.07.081
pubmed: 28751223
Nespoli A, Gianotti L, Bovo G, Brivio F, Nespoli L, Totis M (2006) Impact of postoperative infections on survival in colon cancer patients. Surg Infect (Larchmt) 7(Suppl 2):S41–S43. doi: https://doi.org/10.1089/sur.2006.7.s2-41
doi: 10.1089/sur.2006.7.s2-41
Tsujimoto H, Ichikura T, Ono S, Sugasawa H, Hiraki S, Sakamoto N, Yaguchi Y, Yoshida K, Matsumoto Y, Hase K (2009) Impact of postoperative infection on long-term survival after potentially curative resection for gastric cancer. Ann Surg Oncol 16(2):311–318. doi: https://doi.org/10.1245/s10434-008-0249-8
doi: 10.1245/s10434-008-0249-8
pubmed: 19037699
Tokunaga M, Tanizawa Y, Bando E, Kawamura T, Terashima M (2013) Poor survival rate in patients with postoperative intra-abdominal infectious complications following curative gastrectomy for gastric cancer. Ann Surg Oncol 20(5):1575–1583. doi: https://doi.org/10.1245/s10434-012-2720-9
doi: 10.1245/s10434-012-2720-9
pubmed: 23076557
Tan HJ, Hafez KS, Ye Z, Wei JT, Miller DC (2012) Postoperative complications and long-term survival among patients treated surgically for renal cell carcinoma. J Urol 187(1):60–66. doi: https://doi.org/10.1016/j.juro.2011.09.031
doi: 10.1016/j.juro.2011.09.031
pubmed: 22114816
Kubota T, Hiki N, Sano T, Nomura S, Nunobe S, Kumagai K, Aikou S, Watanabe R, Kosuga T, Yamaguchi T (2014) Prognostic significance of complications after curative surgery for gastric cancer. Ann Surg Oncol 21(3):891–898. doi: https://doi.org/10.1245/s10434-013-3384-9
doi: 10.1245/s10434-013-3384-9
pubmed: 24254205
Hayashi T, Yoshikawa T, Aoyama T, Hasegawa S, Yamada T, Tsuchida K, Fujikawa H, Sato T, Ogata T, Cho H, Oshima T, Rino Y, Masuda M (2015) Impact of infectious complications on gastric cancer recurrence. Gastric Cancer 18(2):368–374. doi: https://doi.org/10.1007/s10120-014-0361-3
doi: 10.1007/s10120-014-0361-3
pubmed: 24634097
Andreou A, Biebl M, Dadras M, Struecker B, Sauer IM, Thuss-Patience PC, Chopra S, Fikatas P, Bahra M, Seehofer D, Pratschke J, Schmidt SC (2016) Anastomotic leak predicts diminished long-term survival after resection for gastric and esophageal cancer. Surgery 160(1):191–203. doi: https://doi.org/10.1016/j.surg.2016.02.020
doi: 10.1016/j.surg.2016.02.020
pubmed: 27067160
pmcid: 27067160
Sierzega M, Kolodziejczyk P, Kulig J, Polish Gastric Cancer Study G (2010) Impact of anastomotic leakage on long-term survival after total gastrectomy for carcinoma of the stomach. Br J Surg 97(7):1035–1042. doi: https://doi.org/10.1002/bjs.7038
doi: 10.1002/bjs.7038
pubmed: 20632269
Yoo HM, Lee HH, Shim JH, Jeon HM, Park CH, Song KY (2011) Negative impact of leakage on survival of patients undergoing curative resection for advanced gastric cancer. J Surg Oncol 104(7):734–740. doi: https://doi.org/10.1002/jso.22045
doi: 10.1002/jso.22045
pubmed: 21792945
Molteni M, Gemma S, Rossetti C (2016) The role of toll-like receptor 4 in infectious and noninfectious inflammation. Mediators Inflamm. https://doi.org/10.1155/2016/6978936
doi: 10.1155/2016/6978936
pubmed: 27293318
pmcid: 4887650
Hoebe K, Beutler B (2006) TRAF3: a new component of the TLR-signaling apparatus. Trends Mol Med 12(5):187–189. doi: https://doi.org/10.1016/j.molmed.2006.03.008
doi: 10.1016/j.molmed.2006.03.008
pubmed: 16621716
Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, Takeuchi O, Sugiyama M, Okabe M, Takeda K, Akira S (2003) Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301(5633):640–643. doi: https://doi.org/10.1126/science.1087262
doi: 10.1126/science.1087262
pubmed: 12855817
Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4(7):499–511. doi: https://doi.org/10.1038/nri1391
doi: 10.1038/nri1391
pubmed: 15229469
Deguine J, Barton GM (2014) MyD88: a central player in innate immune signaling. F1000Prime Rep 6:97. doi: https://doi.org/10.12703/P6-97
doi: 10.12703/P6-97
pubmed: 25580251
pmcid: 4229726
Kagan JC, Medzhitov R (2006) Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling. Cell 125(5):943–955. doi: https://doi.org/10.1016/j.cell.2006.03.047
doi: 10.1016/j.cell.2006.03.047
pubmed: 16751103
Barton GM, Medzhitov R (2003) Toll-like receptor signaling pathways. Science 300(5625):1524–1525. doi: https://doi.org/10.1126/science.1085536
doi: 10.1126/science.1085536
pubmed: 12791976
Gowing SD, Chow SC, Cools-Lartigue JJ, Chen CB, Najmeh S, Jiang HY, Bourdeau F, Beauchamp A, Mancini U, Angers I, Giannias B, Spicer JD, Rousseau S, Qureshi ST, Ferri LE (2017) Gram-positive pneumonia augments non-small cell lung cancer metastasis via host toll-like receptor 2 activation. Int J Cancer 141(3):561–571. doi: https://doi.org/10.1002/ijc.30734
doi: 10.1002/ijc.30734
pubmed: 28401532
Hsu RY, Chan CH, Spicer JD, Rousseau MC, Giannias B, Rousseau S, Ferri LE (2011) LPS-induced TLR4 signaling in human colorectal cancer cells increases beta1 integrin-mediated cell adhesion and liver metastasis. Cancer Res 71(5):1989–1998. doi: https://doi.org/10.1158/0008-5472.CAN-10-2833
doi: 10.1158/0008-5472.CAN-10-2833
pubmed: 21363926
Andrews EJ, Wang JH, Winter DC, Laug WE, Redmond HP (2001) Tumor cell adhesion to endothelial cells is increased by endotoxin via an upregulation of beta-1 integrin expression. J Surg Res 97(1):14–19. doi: https://doi.org/10.1006/jsre.2001.6090
doi: 10.1006/jsre.2001.6090
pubmed: 11319874
Li J, Yin J, Shen W, Gao R, Liu Y, Chen Y, Li X, Liu C, Xiang R, Luo N (2017) TLR4 promotes breast cancer metastasis via Akt/GSK3beta/beta-catenin pathway upon LPS stimulation. Anat Rec (Hoboken) 300(7):1219–1229. https://doi.org/10.1002/ar.23590
doi: 10.1002/ar.23590
Horiguchi H, Tsujimoto H, Shinomiya N, Matsumoto Y, Sugasawa H, Yamori T, Miyazaki H, Saitoh D, Kishi Y, Ueno H (2020) A potential role of adhesion molecules on lung metastasis enhanced by local inflammation. Anticancer Res 40(11):6171–6178. https://doi.org/10.21873/anticanres.14637
doi: 10.21873/anticanres.14637
pubmed: 33109554
Tanaka S, Saito Y, Kunisawa J, Kurashima Y, Wake T, Suzuki N, Shultz LD, Kiyono H, Ishikawa F (2012) Development of mature and functional human myeloid subsets in hematopoietic stem cell-engrafted NOD/SCID/IL2rgammaKO mice. J Immunol 188(12):6145–6155. doi: https://doi.org/10.4049/jimmunol.1103660
doi: 10.4049/jimmunol.1103660
pubmed: 22611244
Skirecki T, Kawiak J, Machaj E, Pojda Z, Wasilewska D, Czubak J, Hoser G (2015) Early severe impairment of hematopoietic stem and progenitor cells from the bone marrow caused by CLP sepsis and endotoxemia in a humanized mice model. Stem Cell Res Ther 6:142. doi: https://doi.org/10.1186/s13287-015-0135-9
doi: 10.1186/s13287-015-0135-9
pubmed: 26272069
pmcid: 4536694
Rodewohl A, Scholbach J, Leichsenring A, Koberle M, Lange F (2017) Age-dependent cellular reactions of the human immune system of humanized NOD scid gamma mice on LPS stimulus. Innate Immun 23(3):258–275. doi: https://doi.org/10.1177/1753425917690814
doi: 10.1177/1753425917690814
pubmed: 28162006
Klaver YL, Hendriks T, Lomme RM, Rutten HJ, Bleichrodt RP, de Hingh IH (2010) Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery for peritoneal carcinomatosis in an experimental model. Br J Surg 97(12):1874–1880. doi: https://doi.org/10.1002/bjs.7249
doi: 10.1002/bjs.7249
pubmed: 20806291
Jacquet P, Sugarbaker PH (1996) Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res 82:359–374
doi: 10.1007/978-1-4613-1247-5_23
Li W, Ng JM, Wong CC, Ng EKW, Yu J (2018) Molecular alterations of cancer cell and tumour microenvironment in metastatic gastric cancer. Oncogene 37(36):4903–4920. doi: https://doi.org/10.1038/s41388-018-0341-x
doi: 10.1038/s41388-018-0341-x
pubmed: 29795331
pmcid: 6127089
Hwang EH, Kim TH, Oh SM, Lee KB, Yang SJ, Park JH (2016) Toll/IL-1 domain-containing adaptor inducing IFN-beta (TRIF) mediates innate immune responses in murine peritoneal mesothelial cells through TLR3 and TLR4 stimulation. Cytokine 77:127–134. doi: https://doi.org/10.1016/j.cyto.2015.11.010
doi: 10.1016/j.cyto.2015.11.010
pubmed: 26579632
Wang J, Feng X, Zeng Y, Fan J, Wu J, Li Z, Liu X, Huang R, Huang F, Yu X, Yang X (2013) Lipopolysaccharide (LPS)-induced autophagy is involved in the restriction of Escherichia coli in peritoneal mesothelial cells. BMC Microbiol 13:255. doi: https://doi.org/10.1186/1471-2180-13-255
doi: 10.1186/1471-2180-13-255
pubmed: 24219662
pmcid: 3833177
Su B, Ceponis PJ, Lebel S, Huynh H, Sherman PM (2003) Helicobacter pylori activates Toll-like receptor 4 expression in gastrointestinal epithelial cells. Infect Immun 71(6):3496–3502
doi: 10.1128/IAI.71.6.3496-3502.2003
Smith MF Jr, Mitchell A, Li G, Ding S, Fitzmaurice AM, Ryan K, Crowe S, Goldberg JB (2003) Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kappa B activation and chemokine expression by epithelial cells. J Biol Chem 278(35):32552–32560. doi: https://doi.org/10.1074/jbc.M305536200
doi: 10.1074/jbc.M305536200
pubmed: 12807870
Yokota S, Okabayashi T, Rehli M, Fujii N, Amano K (2010) Helicobacter pylori lipopolysaccharides upregulate toll-like receptor 4 expression and proliferation of gastric epithelial cells via the MEK1/2-ERK1/2 mitogen-activated protein kinase pathway. Infect Immun 78(1):468–476. doi: https://doi.org/10.1128/IAI.00903-09
doi: 10.1128/IAI.00903-09
pubmed: 19858308
Kawahara T, Teshima S, Oka A, Sugiyama T, Kishi K, Rokutan K (2001) Type I Helicobacter pylori lipopolysaccharide stimulates toll-like receptor 4 and activates mitogen oxidase 1 in gastric pit cells. Infect Immun 69(7):4382–4389. doi: https://doi.org/10.1128/IAI.69.7.4382-4389.2001
doi: 10.1128/IAI.69.7.4382-4389.2001
pubmed: 11401977
pmcid: 98510
Wroblewski LE, Peek RM Jr, Wilson KT (2010) Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev 23(4):713–739. doi: https://doi.org/10.1128/CMR.00011-10
doi: 10.1128/CMR.00011-10
pubmed: 20930071
pmcid: 2952980
Isaza-Restrepo A, Martin-Saavedra JS, Velez-Leal JL, Vargas-Barato F, Riveros-Duenas R (2018) The peritoneum: beyond the tissue—a review. Front Physiol 9:738. https://doi.org/10.3389/fphys.2018.00738
doi: 10.3389/fphys.2018.00738
pubmed: 29962968
pmcid: 6014125
Yung S, Chan TM (2012) Pathophysiological changes to the peritoneal membrane during PD-related peritonitis: the role of mesothelial cells. Mediators Inflamm. https://doi.org/10.1155/2012/484167
doi: 10.1155/2012/484167
pubmed: 22577250
pmcid: 3337720
Cui L, Johkura K, Liang Y, Teng R, Ogiwara N, Okouchi Y, Asanuma K, Sasaki K (2002) Biodefense function of omental milky spots through cell adhesion molecules and leukocyte proliferation. Cell Tissue Res 310(3):321–330. doi: https://doi.org/10.1007/s00441-002-0636-6
doi: 10.1007/s00441-002-0636-6
pubmed: 12457231
Chow SC, Gowing SD, Cools-Lartigue JJ, Chen CB, Berube J, Yoon HW, Chan CH, Rousseau MC, Bourdeau F, Giannias B, Roussel L, Qureshi ST, Rousseau S, Ferri LE (2015) Gram negative bacteria increase non-small cell lung cancer metastasis via Toll-like receptor 4 activation and mitogen-activated protein kinase phosphorylation. Int J Cancer 136(6):1341–1350. doi: https://doi.org/10.1002/ijc.29111
doi: 10.1002/ijc.29111
pubmed: 25082668
Gowing SD, Chow SC, Cools-Lartigue JJ, Chen CB, Najmeh S, Goodwin-Wilson M, Jiang HY, Bourdeau F, Beauchamp A, Angers I, Giannias B, Spicer JD, Rousseau S, Qureshi ST, Ferri LE (2019) Gram-Negative pneumonia augments non-small cell lung cancer metastasis through host toll-like receptor 4 activation. J Thorac Oncol 14(12):2097–2108. https://doi.org/10.1016/j.jtho.2019.07.023
doi: 10.1016/j.jtho.2019.07.023
pubmed: 31382038
Yang Y, Qiu Y, Tang M, Wu Z, Hu W, Chen C (2017) Expression and function of transforming growth factorbetaactivated protein kinase 1 in gastric cancer. Mol Med Rep 16(3):3103–3110. doi: https://doi.org/10.3892/mmr.2017.6998
doi: 10.3892/mmr.2017.6998
pubmed: 28714004
pmcid: 5548047
Lai AZ, Cory S, Zhao H, Gigoux M, Monast A, Guiot MC, Huang S, Tofigh A, Thompson C, Naujokas M, Marcus VA, Bertos N, Sehat B, Perera RM, Bell ES, Page BD, Gunning PT, Ferri LE, Hallett M, Park M (2014) Dynamic reprogramming of signaling upon met inhibition reveals a mechanism of drug resistance in gastric cancer. Sci Signal 7(322):ra38. doi: https://doi.org/10.1126/scisignal.2004839
doi: 10.1126/scisignal.2004839
pubmed: 24757178
Burnett A, Lecompte MA, Trabulsi N, Dube P, Gervais MK, Trilling B, Cloutier AS, Sideris L (2019) Peritoneal carcinomatosis index predicts survival in colorectal patients undergoing HIPEC using oxaliplatin: a retrospective single-arm cohort study. World J Surg Oncol 17(1):83. doi: https://doi.org/10.1186/s12957-019-1618-4
doi: 10.1186/s12957-019-1618-4
pubmed: 31092250
pmcid: 6521370
Elias D, Faron M, Iuga BS, Honore C, Dumont F, Bourgain JL, Dartigues P, Ducreux M, Goere D (2015) Prognostic similarities and differences in optimally resected liver metastases and peritoneal metastases from colorectal cancers. Ann Surg 261(1):157–163. doi: https://doi.org/10.1097/SLA.0000000000000582
doi: 10.1097/SLA.0000000000000582
pubmed: 24509197
Leiting JL, Grotz TE (2018) Optimizing outcomes for patients with gastric cancer peritoneal carcinomatosis. World J Gastrointest Oncol 10(10):282–289. doi: https://doi.org/10.4251/wjgo.v10.i10.282
doi: 10.4251/wjgo.v10.i10.282
pubmed: 30364780
pmcid: 6198298
Chia CS, You B, Decullier E, Vaudoyer D, Lorimier G, Abboud K, Bereder JM, Arvieux C, Boschetti G, Glehen O, Group BR (2016) Patients with peritoneal carcinomatosis from gastric cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: is cure a possibility? Ann Surg Oncol 23(6):1971–1979. https://doi.org/10.1245/s10434-015-5081-3
doi: 10.1245/s10434-015-5081-3
pubmed: 26753751
da Silva RG, Sugarbaker PH (2006) Analysis of prognostic factors in seventy patients having a complete cytoreduction plus perioperative intraperitoneal chemotherapy for carcinomatosis from colorectal cancer. J Am Coll Surg 203(6):878–886. doi: https://doi.org/10.1016/j.jamcollsurg.2006.08.024
doi: 10.1016/j.jamcollsurg.2006.08.024
pubmed: 17116556
Chua TC, Saxena A, Schellekens JF, Liauw W, Yan TD, Fransi S, Zhao J, Morris DL (2010) Morbidity and mortality outcomes of cytoreductive surgery and perioperative intraperitoneal chemotherapy at a single tertiary institution: towards a new perspective of this treatment. Ann Surg 251(1):101–106. doi: https://doi.org/10.1097/SLA.0b013e3181b5ae43
doi: 10.1097/SLA.0b013e3181b5ae43
pubmed: 19838105
Mizumoto A, Canbay E, Hirano M, Takao N, Matsuda T, Ichinose M, Yonemura Y (2012) Morbidity and mortality outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at a single institution in Japan. Gastroenterol Res Pract. https://doi.org/10.1155/2012/836425
doi: 10.1155/2012/836425
pubmed: 22956941
pmcid: 3432358
Liu JY, Yuan JP, Geng XF, Qu AP, Li Y (2015) Morphological study and comprehensive cellular constituents of milky spots in the human omentum. Int J Clin Exp Pathol 8(10):12877–12884
pubmed: 26722479
pmcid: 4680424
Muccioli M, Benencia F (2014) Toll-like receptors in ovarian cancer as targets for immunotherapies. Front Immunol 5:341. https://doi.org/10.3389/fimmu.2014.00341
doi: 10.3389/fimmu.2014.00341
pubmed: 25101083
pmcid: 4105689
Kelly MG, Alvero AB, Chen R, Silasi DA, Abrahams VM, Chan S, Visintin I, Rutherford T, Mor G (2006) TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer. Cancer Res 66(7):3859–3868. doi: https://doi.org/10.1158/0008-5472.CAN-05-3948
doi: 10.1158/0008-5472.CAN-05-3948
pubmed: 16585214
Franchi L, Warner N, Viani K, Nunez G (2009) Function of Nod-like receptors in microbial recognition and host defense. Immunol Rev 227(1):106–128. doi: https://doi.org/10.1111/j.1600-065X.2008.00734.x
doi: 10.1111/j.1600-065X.2008.00734.x
pubmed: 19120480
pmcid: 2679989
Correa P (2004) The biological model of gastric carcinogenesis. IARC Sci Publ 157:301–310
Matsuo K, Prather CP, Ahn EH, Eno ML, Tierney KE, Yessaian AA, Im DD, Rosenshein NB, Roman LD (2012) Significance of perioperative infection in survival of patients with ovarian cancer. Int J Gynecol Cancer 22(2):245–253. doi: https://doi.org/10.1097/IGC.0b013e31823bd6db
doi: 10.1097/IGC.0b013e31823bd6db
pubmed: 22228425