Comprehensive modeling of the Correa cascade in precancerous lesions of gastric cancer: Leveraging animal, cellular, and organoid systems for translational insights

Table 1 Summary of modeling methods, agents, and animal types used in precancerous lesions of gastric cancer research

Type	Modeling method	Model animals	Modeling time	Observation time	Atrophy	Metaplasia	Dysplasia	Carcinoma	Ref.
MNU	MNU (120 ppm)	C57BL/6 mice	8 weeks	8 weeks	Yes	IM	Yes	No	[19]
	MNU (100-120 ppm)	BALB/c and C57BL/6 mice, Wistar rats	16-30 weeks	31-54 weeks	Yes	Yes	Yes	Yes	[20,72]
	MNU (120 ppm)	db/db mice	20 weeks	30 weeks	No	No	Yes	Yes	[73]
	MNU (300 ppm)	BALB/c mice	16 weeks	16 weeks	No	IM (16 weeks)	No	No	[74]
MNNG	MNNG (200 μg/mL)	SD rats	16 weeks	26 weeks	No	IM (16 weeks)	Yes (16 weeks)	No	[10,75]
	MNNG (200 μg/mL)	SD rats	40 weeks	40 weeks	No	No	Yes (40 weeks)	Yes (40 weeks)	[9]
	MNNG (800 mg/L)	SD rats	10 weeks	34 weeks	Yes (10 weeks)	No	Yes (22 weeks)	Yes (34 weeks)	[11]
	MNNG (150 μg/mL)	BALB/c mice, C57BL/6 mice	6 weeks	14-36 weeks	Yes	IM	Yes	No	[12,13]
CDCA	DCA (0.2%)	INS-GAS mice	6 months	6 months	Yes (5 months)	IM	Yes	No	[23]
	CDCA (20 mmol/L) + 2% sodium salicylate	SD rats	12 weeks	12 weeks	Yes	IM	No	No	[24,25]
	CDCA (20 mmol/L) + 0.1% ammonia + irregular diet	SD rats	16 weeks	16 weeks	Yes				[26]
Acute drug and H. pylori induction	DMP-777	CD-1 rats, C57BL/6 mice	7-14 days	7-14 days	SPEM	No	No	No	[30,76]
	L635	C57BL/6 mice	3 days	3 days	SPEM	No	No	No	[77]
	Tamoxifen (250 mg/kg)	C57BL/6 mice	3 days	3 days	SPEM	Yes	No	No	[31,32]
	Tamoxifen (50 mg/kg)	gp130Y757F/Y757F mice	2 days	16 weeks	SPEM	Yes	Yes	Yes	[33]
	CagA-positive PMSS1	C57BL/6 mice, Tert-/- mice	12 weeks	12 weeks	SPEM	No	No	No	[34]
H. pylori strain	H. felis	C57BL/6 mice	15 months	15 months	Yes	Yes	Yes	Yes	[39]
	H. pylori SS1	C57BL/6 mice	18 months	18 months	Yes	Yes	No	No	[42]
	H. pylori PMSS1	C57BL/6 mice	8 weeks	8 weeks	Yes	Yes	No	No	[43]
	H. pylori HpslyD + strain	C57BL/6 mice	73 weeks	73 weeks	Yes	IM	No	No	[47]
	H. pylori TN2GF4 strain	Mongolian gerbils	18 weeks	18 weeks	Yes (2 weeks)	IM	No	No	[50]
	H. pylori ATCC 43504 strain	Mongolian gerbils	16-18 months	16-18 months	Yes	IM	Yes	Yes	[49]
	H. pylori 7.13 strain	Mongolian gerbils	7-9 weeks	7-9 weeks	Yes	IM (7 weeks)	Yes	Yes (9 weeks)	[52]
Non-H. pylori gastric microbiome	S. anginosus	C57BL/6 mice, germ-free BALB/c mice	48 weeks	48 weeks	Yes (9 months)	Yes (12 months)	Yes (12 months)	No	[53]
	S. anginosus + MNU (240 ppm)	C57BL/6 mice	36 weeks	36 weeks	Yes	Yes	Yes	Yes (9 months)	[53]
MNU + H. pylori	MNU (240 ppm) + HpSS1	C57BL/6 mice	12-16 weeks	50-80 weeks	Yes	IM	Yes	Yes	[55]
	MNU (200 ppm) + H. felis	FVB and B6 mice	36 weeks	36-50 weeks	Yes	Yes	Yes	Yes	[54,78]
	MNU + PMSS1	C57BL/6 mice	12 weeks	40 weeks	Yes	IM	Yes	No	[56]
	MNU (10 ppm) + ATCC 43504	Mongolian gerbil	24 weeks	53 weeks	Yes	IM	Yes	No	[57]
MNU + dietary	MNU (120 ppm) + 10% NaCl	C57BL/6J mice	40 weeks	40 weeks				Yes	[36]
	MNU (120 ppm) + HpSS1 + 10% NaCl	C57BL/6J mice	40 weeks	40 weeks				Yes	[36]
	MNU + DCA	C57BL/6 mice, Lgr5-p53-/- mice	48 weeks	48 weeks		Yes	Yes	No	[59]
	MNU (300 ppm) + irregular diet	BALB/c mice	20 weeks	20 weeks	Yes	IM	Yes	No	[58]
MNNG + H. pylori	MNNG (50 μg/mL) + KMUH-G926	Mongolian gerbil	20 weeks	52 weeks	Yes (32 weeks)	No	Yes	Yes (52 weeks)	[71]
	MNNG (40 μg/mL) + HpSS1	C57BL/6J mice	48 weeks	48 weeks	No	No	Yes (48 weeks)	No	[7]
MNNG composite model	MNNG (200 μg/mL) + saturated salt	Wistar rats	25 weeks	35 weeks	Yes (25 weeks)	IM	Yes (35 weeks)	No	[61]
	MNNG (200 μg/mL) + 0.1% ammonia + irregular fasting	SD rats	20 weeks	20 weeks	Yes	IM	Yes	No	[60]
	MNNG (120 μg/mL) + H. pylori + ammonia	Kunming mice	7 days	120 days	Yes	No	No	No	[16]
	MNNG (170-200 μg/mL) + irregular diet	SD rats, Wistar rats	10-12 weeks	14 weeks	Yes	No	No	No	[62,63]
	MNNG (200 μg/mL) + irregular diet + emotionally stimulated	Wistar rats	24 weeks	24 weeks	Yes	IM	Yes	No	[64]
	MNNG (100 μg/mL) + 2% sodium salicylate	Wistar rats	17 weeks	21 weeks	Yes	IM	Yes	No	[65]
	MNNG (120 μg/mL) + 5% aqueous alcohol solution	Wistar rats	56 weeks	56 weeks	No	No	No	Yes (14 months)	[66]
	MNNG (120-150 μg/mL) + 2% sodium salicylate + irregular fasting + 0.05% ranitidine	Wistar rats	32-40 weeks	32-40 weeks	Yes	Yes	Yes	Yes	[67,68,70]
	MNNG (200 μg/mL) + 40% alcohol + irregular fasting + 0.03% ranitidine	SD rats	40 weeks	40 weeks	Yes	IM	Yes	No	[69]

MNU: N-Nitroso-N-methylurea; MNNG: N-methyl-N’-nitro-N-nitrosoguanidine; CDCA: Chenodeoxycholic acid; H. pylori: Helicobacter pylori; DCA: Deoxycholic acid; H. felis: Helicobacter felis; S. anginosus: Streptococcus anginosus; HpSS1: Helicobacter pylori Sydney strain; INS-GAS: Insulin-gastrin; SD: Sprague-Dawley; Lgr5: Leucine-rich repeat-containing G protein-coupled receptor 5; IM: Intestinal metaplasia.