Introduction

Programmed cell death ligand-1 (PD-L1) is known to negatively regulate T-cell activation. Immune checkpoint inhibitors (ICIs) such as nivolumab and pembrolizumab have prolonged survival in gastric cancer (GC) as well as malignant melanoma and lung cancer.

Aims & Methods

The aim of this study was to investigate the affecting factors on the expression of PD-L1 in GC tissue in the Korean population in terms of clinicopathological variables.
Total 216 patients with GC who underwent PD-L1 immunohistochemistry (22C3) were prospectively enrolled at Seoul National University Bundang Hospital from March 2018 to February 2024. Positive PD-L1 expression was defined as a CPS score of 5 or higher. Univariate and multivariate analysis was performed.

Results

Table.Univariate and Multivariate analysis for affecting factors on PD-L1 expression

		Univariate analysis		Multivariate analysis
Variables		OR (95% CI)	p value	OR (95% CI)	p value
EBV infection	EBV negative	Ref.		Ref.
	EBV positive	8.54 (1.59-158.42)	0.043	14.01 (2.23-278.16)	0.019
Tumor location	Non-cardia	Ref.		Ref.
	Cardia	2.78 (1.18-7.35)	0.026​	4.97 (1.17-16.08)	0.005
TNM stage	Stage I	Ref.		Ref.
	Stage II,III, or IV	1.38 (1.00-1.92)	0.049	1.61 (1.09-2.42)	0.018

Multivariate regression (Table) showed some few significant associations between PD-L1 expression and specific factors. EBV infection shows a strong effect in both univariate (odd ratio [OR] 8.54, 95% confidence interval [CI] 1.59-158.42, p=0.043) and multivariate analysis(OR 14.01, CI 2.23-278.16, p=0.019). Cardia portion involvement shows a significant correlation in both univariate (OR 2.78, CI 1.18-7.35, p=0.026) and multivariate analysis(OR 4.97, CI 1.71-16.08, p=0.005). And higher TNM stage also remains significant in both univariate (OR 1.38, CI 1.00-1.92, p=0.049) and multivariate analysis (OR 1.61, CI 1.09-2.42, p=0.018).

Conclusion

EBV infection, cardia involvement, and higher TNM stage were independent factors influencing PD-L1 expression.

Introduction

Gastric cancer (GC) remains one of the most lethal malignancies worldwide, with limited treatment success largely due to immune evasion and tumor heterogeneity ¹. The advent of immune checkpoint inhibitors has revolutionized the treatment of solid tumors ²; however, only a subset of GC patients benefits from PD-1/PD-L1 blockade, suggesting the presence of intrinsic mechanisms regulating immune escape ³. Leukemia Inhibitory Factor (LIF), a multifunctional interleukin (IL)-6 cytokine family, plays an essential role in epithelial repair, embryonic stem cell pluripotency, and immune regulation ⁴. In several type of tumors, LIF is emerging as a key mediator of tumor progression and immune modulation. LIF signals through a heterodimeric receptor complex composed of LIF-receptor (LIFR) and GP130 and promotes JAK/STAT3 pathway activation ^5,6. Notably, oncogenic STAT3 signaling has been shown to drive PD-L1 expression and promote immune suppression across multiple tumor types, including breast cancer ⁷ and NK/T-cell lymphoma, supporting the broader relevance of this axis in tumor immune escape ⁸. Although LIF is known to activate JAK/STAT3 signaling ⁴, its role in regulating PD-L1 expression and establishing an immunosuppressive microenvironment in GC is not fully defined.

Aims & Methods

We aimed to dissect the role of LIF in promoting PD-L1 expression and immune escape in GC and to explore the therapeutic potential of LIF inhibition. Neoplastic and non-neoplastic gastric mucosa from 61 GC patients were analyzed by transcriptomic profiling, immunofluorescence (IF), and tSNE analysis. Expression levels of LIF, PD-L1, and key signaling molecules were quantified. In vitro mechanistic studies, employed human gastric cancer cells (MKN45). MKN45 were exposed to recombinant LIF, with or without LRI-305, a novel LIF receptor antagonist. Western blotting, RT-qPCR, IF, and chromatin immunoprecipitation (ChIP) assays were used to evaluate downstream pathway activation and transcriptional regulation of PD-L1.

Results

Transcriptome analysis revealed a significant upregulation of LIF and PD-L1 in tumor samples, which was confirmed at the protein level by Immunofluorescence analysis. Elevated LIF expression correlated with reduced overall survival and an immunosuppressive tumor microenvironment characterized by increased infiltration of PD1⁺ T cells, Tregs, and LIF⁺ TAM. Functional assays demonstrated that LIF stimulation activated the JAK1/STAT3 pathway, leading to enhanced PD-L1 transcription. This was supported by increased phosphorylation of JAK1 and STAT3 and ChIP data confirming STAT3 recruitment to the PD-L1 promoter. LIF also promoted cell proliferation and epithelial-mesenchymal transition (EMT), indicated by upregulation of SNAIL1. Importantly, LRI-305 treatment abolished these effects, downregulating PD-L1 expression, reducing EMT markers, and restoring pro-apoptotic responses. These findings confirmed that LIF sustains tumor growth and play a pivotal role in immune resistance through STAT3-mediated PD-L1 upregulation.

Conclusion

Our data identify the LIF/STAT3/PD-L1 axis as a crucial pathway driving immune evasion in GC. LIF promotes a tolerogenic tumor microenvironment, impairs anti-tumor immunity and correlates with aggressive tumor behavior and poor prognosis. Pharmacological blockade of LIF signaling using LRI-305 effectively reverses these effects, offering a novel combinatorial strategy to enhance the efficacy of immune checkpoint inhibitors in GC patients.

References

1. Smyth, E. C. et al. Gastric cancer. Lancet 396, 635–648 (2020).
2. Ribas, A. & Wolchok, J. D. Cancer immunotherapy using checkpoint blockade. Science 359, 1350–1355 (2018).
3. Fuchs, C. S. et al. Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncol. 4, e180013 (2018).
4. Di Giorgio, C. et al. Next-Generation Sequencing Analysis of Gastric Cancer Identifies the Leukemia Inhibitory Factor Receptor as a Driving Factor in Gastric Cancer Progression and as a Predictor of Poor Prognosis. Front. Oncol. 12, 939969 (2022).
5. Pascual-García, M. et al. LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8(+) T cell tumor-infiltration impairing anti-PD1 therapy. Nat. Commun. 10, 2416 (2019).
6. Yu, S. et al. Tumor-derived LIF promotes chemoresistance via activating tumor-associated macrophages in gastric cancers. Exp. Cell Res. 406, 112734 (2021).
7. Zerdes, I. et al. STAT3 Activity Promotes Programmed-Death Ligand 1 Expression and Suppresses Immune Responses in Breast Cancer. Cancers (Basel). 11, (2019).
8. Song, T. L. et al. Oncogenic activation of the STAT3 pathway drives PD-L1 expression in natural killer/T-cell lymphoma. Blood 132, 1146–1158 (2018).

Introduction

Epstein-Barr virus (EBV) associated gastric cancer (GC) has been reported to be about 5-16% of all gastric cancers with good prognosis compared to EBV-negative GC. The aim of this study was to evaluate the clinicopathological characteristics of EBV-positive GC including survival analysis in the prospective observational cohort study in a tertiary hospital in South Korea.

Aims & Methods

Total 4,586 patients who underwent EBV in situ hybridization (EBV-ISH) testing among 14,613 patients diagnosed with GC were prospectively enrolled at Seoul National University Bundang Hospital from 2003 to 2023. Data including age, sex, smoking, cancer type and stage, tumor size and location, histologic type, molecular features (p53 expression and MSI), and survival information including causes of death were collected and analyzed.

Results

EBV-positive cancer group showed significant differences compared to EBV-negative cancer group. That is, they showed higher proportion of males (p<0.001), predominant presence in the proximal stomach (p<0.001), higher proportion of undifferentiated cancer (p<0.001), and lower cancer stage (p=0.004) (Table). In Cox multivariate analyses, age (HR 1.022, p<0.001), tumor size (HR 1.118, p<0.001) along with cancer stage (stage 2 HR 5.843, p<0.001; stage3 HR 15.570, p<0.001; stage4 HR 50.075, p<0.001, respectively) were significant risk factors for GC-specific mortality, while EBV positivity was inversely correlated (HR 0.537, p=0.023). In the survival analyses, EBV-positive cancer group showed statistically significant survival advantages over EBV-negative cancer group in both overall (p=0.016) and gastric cancer-specific survival (p=0.005)

Variables		Total patients (n=4,586) (%)	EBV positive (n=456) (%)	EBV negative (n=4,130) (%)	P value
Sex	Male	3028 (66)	404 (88.6)	2624 (63.5)	<0.001
	Female	1558 (34)	52 (11.4)	1503 (36.5)
Location (n=4,579)	Cardia, Body	2076 (45.3)	367 (80.5)	1709 (41.5)	<0.001
	Antrum	2503 (54.7)	89 (19.5)	2414 (58.5)
Histology type (n=3,799)	Differentiated	1891 (49.8)	123 (35.5)	1768 (51.2)	<0.001
	Undifferentiated	1908 (50.2)	223 (64.5)	1685 (48.8)
TNM staging	1	2818 (61.4)	316 (69.3)	2502 (60.6)	0.001
	2	683 (14.9)	52 (11.4)	631 (15.3)
	3 or above	1085 (23.7)	88 (19.3)	997 (24.1)

Overall survival
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GC-specific survival
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Conclusion

EBV-positive GC group was associated with male sex, proximal location, poorly differentiated histology and lower cancer stage, and showed significantly better prognosis than EBV-negative gastric cancer. EBV might play a role in the gastric carcinogenesis to make less metastasis resulting in better survival.

Introduction

The sex differences in the incidence of gastric cancer have been well known. However, uncertainty still exists in terms of prognosis of GC. For example, the US SEER data reports a significantly better prognosis in females than in males, but the prognosis is better in males than in females in Korean Central Cancer Registry data. Roles of molecular markers and gut microbiota as new prognostic factor are emerging recently, but few studies seem to try to reveal sex differences.

Aims & Methods

In this background, we aimed to analyze the differences in GC characteristics according to sex in Korean patients, mainly focused on survival. This was a single-center retrospective study. A total of fifteen thousand patients diagnosed with GC at the Seoul National University Bundang Hospital between 2003 and 2023 were included. Clinicopathological characteristics, histologic types, survival rates with age- and stage-stratification, and associated risk factors were analyzed. Information related to death was cross-verified using medical record review and data from the National Statistical Office.

Results

The ratio of males and females was about 2:1, and there was no differences in stage between sexes. Female patients were significantly younger than males, had more gastric body cancers and tumors with diffuse type or poorly differentiated histology. Females underwent less endoscopic treatment and more surgery, and tumors with microsatellite instability was more common in females, while mutation of p53 was less common. In histological types according to Lauren classification, diffuse type histology was more common in younger patients in both males and females. The proportion of intestinal type GC increased with age, but the proportion increased rapidly in males while increased gradually in females. In Cox multivariate regression analysis for GC-related death, older age, proximal tumor location, diffuse type histology and advanced tumor stage were risk factors. In terms of survival, overall and GC-specific survival did not show significant differences between sexes in the analysis of the total population. However, sex differences in survival reversed with age, that younger females under 50 showed survival disadvantages, but the survival became similar in 50s, and older females over 60 showed survival advantages in both overall and GC-specific survival. Furthermore, in the stratification analysis according to the stage, there were no significant differences in stages I to III. But, stage IV female patients showed significant survival disadvantages. In subgroup analysis of stage IV patients, the differences between males and females in median survival were two months, and female patients were significantly younger and had a higher proportion of diffuse type GC than male patients, which shows aggressive feature and is related to poorer survival.

		Total (N=1,924) (%)	Male (n=1,282) (%)	Female (n=642) (%)	p
Median survival (mo)		10	11	9	0.022
Age (mean±SD)		61.59±14.25	62.41±13.23	59.96±15.97	0.001
Age (in diffuse type patients, mean±SD)		54.55±14.71	56.43±14.29	52.26±14.91	0.001
Lauren classification	Intestinal	554 (48.0)	438 (56.7)	116 (30.4)	<0.001
	Diffuse	574 (49.7)	315 (40.7)	259 (68.0)
	Mixed / Indeterminate	26 (2.3)	20 (2.6)	6 (1.6)

Conclusion

Significant differences in survival between sexes were observed with stratification analysis, although sex itself was not an independent prognostic factor. These age-dependent changes are thought to suggest the effect of sex hormones. These differences should be considered in clinical practice and later research in terms of tailored medicine.

Introduction

Serum pepsinogens (PGs) are the biomarkers for atrophic gastritis and severe gastric inflammation.

Aims & Methods

The aim of this study was to validate the role of PGs in gastric cancer (GC) screening. 1,705 gastric neoplasms (1,287 GC and 418 gastric adenoma (GA)) and 21,425 controls (total 23,130) were enrolled. PGs and anti-Helicobacter pylori (HP) antibody were measured. Area under the curve and receiver operating characteristic curve were calculated to identify the optimal cutoff values for PGs. Multivariate logistic regression and risk stratification were conducted by combining each PG value and anti-HP antibody in GC subtypes.

Characteristics		Total (23,130) (%)	Control (21,425) (%)	Gastric Adenoma (418) (%)	GC (1,287) (%)	p	Intestinal -GC 762 (%)	Diffuse- GC (489) (%)	p
Sex	Female	8,897 (38.5)	8,358 (39.0)	134 (32.1)	405 (31.5)	<0.001	175 (23.0)	219 (44.8)	<0.001
	Male	14,233 (61.5)	13,067 (61.0)	284 (67.9)	882 (68.5)		587 (77.0)	270 (55.2)
Age (mean)		54	54	63	62	<0.001	64	55	<0.001
HP status	Negative	8,119 (35.1)	7,857 (36.7)	54 (12.9)	208 (16.2)	<0.001	137 (18.0)	61 (12.5)	0.008
	Positive	15,009 (64.9)	13,566 (63.3)	364 (87.1)	1,079 (83.8)		625 (82.0)	428 (87.5)
	Missing	2 (0.0)	2 (0.0)	0 (0.0)	0 (0.0)		0 (0.0)	0 (0.0)
PG series (ng/mL)	PGI	52.1 (28.8)	52.4 (27.9)	40.3 (38.85)	50.6 (50.2)	<0.001	44 (42.65)	60.2 (56.75)	<0.001
	PGII	11.2 (10.8)	11.0 (10.3)	12.9 (11.7)	17.5 (19.2)	<0.001	16 (16.63)	21.2 (21.0)	<0.001
	PGI/II ratio	4.6 (2.6)	4.8 (2.6)	3.0 (2.4)	2.9 (2.3)	<0.001	2.9 (2.4)	2.9 (2.1)	0.328

GC, gastric cancer; HP, Helicobacter pylori; PG, pepsinogen.

Results

PGII ≥21 ng/ml was associated with the risk of GA (odds ratio (OR) 1.38, p<0.001), GC (OR 2.77, p<0.001), diffuse-type GC (DGC) (OR 4.26, p<0.001), especially, early-stage DGC (OR 7.11, p<0.001). When GC risk was assessed by combining each PG value and HP antibody, OR showed significance between categories, and even stepwise increment from HP negative to positive and from each PG value negative to positive after adjustment with other confounding GC risk factors.

Conclusion

Each PG value combining HP test can be used as a screening test for high risk subjects with GC, and especially the combination of PGII≥21ng/ml and positive HP status in young female was related to high risk of early-stage DGC.

Introduction

Early gastric cancer (EGC) refers to adenocarcinoma confined to the mucosa or submucosa, regardless of lymph node status. It is increasingly detected due to the widespread implementation of upper gastrointestinal endoscopy, particularly in East Asia. For intramucosal EGC (T1a), endoscopic resection such as endoscopic submucosal dissection (ESD) has been established as the standard of care, given its low risk of lymph node metastasis (LNM) and favorable long-term outcomes. However, the management of submucosal invasive EGC (T1b) remains controversial. The Japan Gastroenterological Endoscopy Society (JGES) recommends additional surgical resection with lymphadenectomy following ESD if pathological evaluation indicates T1b invasion, due to the significantly increased LNM risk. Nonetheless, many patients who undergo surgery for T1b EGC are ultimately found to be node-negative, raising concerns regarding overtreatment and its associated morbidity. This study aimed to evaluate real-world data from a tertiary center in Taiwan to clarify the necessity of additional surgical intervention after ESD in T1b cases.

Aims & Methods

This retrospective cohort study analyzed data from patients diagnosed with EGC between January 2011 and December 2022 at Kaohsiung Chang Gung Memorial Hospital. Inclusion criteria were histologically confirmed Tis, T1a, or T1b gastric adenocarcinoma treated with either ESD or surgical resection. Patients with gastrointestinal stromal tumors, neuroendocrine neoplasms, or advanced-stage disease were excluded. Depth of invasion was evaluated preoperatively using endoscopic ultrasonography (EUS), and pathological staging was confirmed on resected specimens. Patients in the ESD group with submucosal invasion (T1b) were further assessed for curative resection status based on en bloc resection, margin negativity, and absence of lymphovascular invasion. Those with non-curative ESD were referred for additional gastrectomy and lymph node dissection. LNM rates and nodal staging were analyzed based on surgical pathology.

Results

A total of 753 patients met the inclusion criteria, comprising 663 in the surgical group and 90 in the ESD group. Among those undergoing surgery, 124 patients had T1b tumors. Of these, 25 (20.1%) had pathologically confirmed LNM, the majority of which were classified as N1 disease (14/25, 56%), indicating involvement of one to two regional lymph nodes. In contrast, 3 patients in the ESD group were found to have T1b lesions on final pathology. All three underwent additional gastrectomy and lymphadenectomy despite negative margins and no lymphovascular invasion in the initial ESD specimens. None of these patients had detectable LNM post-surgery. Overall, the ESD group showed no cases of local or distant recurrence during follow-up.

Conclusion

Our 10-year institutional data suggest that approximately one in five patients with T1b EGC harbor LNM, with most cases limited to N1 involvement. While current guidelines advocate for additional surgery in T1b EGC to address potential occult metastasis, our findings suggest that in selected patients with favorable pathological features—such as negative margins, no lymphovascular invasion, and limited submucosal depth—ESD alone may be sufficient. This underscores the need for individualized risk stratification models incorporating endoscopic, histologic, and molecular factors to avoid unnecessary surgical morbidity. Prospective studies are warranted to validate such models and optimize treatment pathways for T1b gastric cancer in the era of minimally invasive therapy.

References

1. Sun W, Liu S, Zhang H, et al. Risk factors and clinicopathological characteristics of lymph node metastasis in T1b gastric cancer: A multicenter retrospective study. Cancer Med. 2022;11(11):2234–2243. doi:10.1002/cam4.4602
2. Shichijo S, Uedo N, Kanesaka T, et al. Long-term outcomes after endoscopic submucosal dissection for differentiated-type early gastric cancer that fulfilled expanded indication criteria: a prospective cohort study. J Gastroenterol Hepatol. 2020;35(1):74–81. doi:10.1111/jgh.14780
3. Zhang L, Liu H, Xu C, et al. Lymph node metastasis and prognostic analysis in early gastric cancer: a single-center experience with 1,011 cases. J Gastric Cancer. 2024;24(1):45–53. doi:10.5230/jgc.2024.24.e5
4. Kim YI, Kim CG, Lee JY, et al. Long-term outcomes of endoscopic submucosal dissection with or without additional surgery for T1b gastric cancer. Ann Surg Oncol. 2023;30(5):1234–1242. doi:10.1245/s10434-022-12600-3
5. Fang WL, Huang KH, Chen JH, et al. The risk factors of lymph node metastasis in early gastric cancer. Pathol Oncol Res. 2015;21(4):941–946. doi:10.1007/s12253-015-9920-0
6. Choi KK, Bae JM, Kim SM, et al. The risk of lymph node metastases in 3951 surgically resected mucosal gastric cancers: implications for endoscopic resection. Gastrointest Endosc. 2016;83(5):896–901. doi:10.1016/j.gie.2015.08.052

Introduction

Gastric Cancer (GC) is one of the most common carcinomas world-wide (1) characterised by a peculiar contribution of the tumour microenvironment to the aggressive biology of this malignancy (2). GC progression is characterised by striking changes in lymphatic vessels (LVs) and lymphatic metastasis is the most common feature of GC spread, representing the most significant prognostic factor determining clinical outcomes (3). Recent publications have demonstrated a functional link between the Extra-Cellular Matrix protein EMILIN-1, tumor growth, and lymphangiogenesis. EMILIN-1 is a key structural and functional element in the maintenance of a competent lymphatic vasculature and, as demonstrated in skin and colitis-associated cancer mouse models, exhibits anti-proliferative and oncosuppressive properties through the interaction with α4β1 integrin (4,5,6).

Aims & Methods

We have observed that EMILIN1 is present at lower levels in human gastric malignant and pre-neoplastic samples and this correlates with the presence of abnormal LVs (unpublished preliminary data). The aim of this study is to investigate the role of EMILIN-1 in gastric tumor onset and progression using mouse models of GC.
We used the syngeneic YTN16 gastric cancer cell line (7) in genetically modified EMILIN-1 mice (KO, knock out mice; E933A KI, E933A-mutated Emilin1 Knock-In animals expressing an EMILIN-1 mutant that is unable to interact with α4/α9β1 integrins). KI animals were included to specifically define the effects related to integrin engagement. Cells were injected intraperitoneally (i.p.), sub-cutaneously (s.c.) or into the footpad of 8-week-old C57BL/6 mice; tumors were analyzed after 3 weeks. A protocol using N-methyl-N-nitrosourea (MNU) was also performed on the same animal models to better investigate the role of EMILIN-1 when a chemically-induced gastric carcinogenesis approach was used. Mice were given drinking water ad libitum containing 240 ppm MNU on alternate weeks for a total exposure of 5 weeks and sacrificed after 30 weeks.

Results

To assess tumor growth, mice were injected with the syngeneic GC cell line YTN16 subcutaneously into both flanks. KO and E933A KI mice developed larger and earlier tumors; tumor samples were stained with Lyve-1 and CD31 to identify lymphatic and blood vessels, respectively. While no differences were observed for CD31-positive structures, a statistically significant increase in intratumoral lymphangiogenesis was observed in KO and E933A KI animals. Lymphatic spread was analyzed in detail by means of intra-footpad injection; enhanced lymph node (LN) metastasis of YTN16 transplanted tumors was observed in KO and E933A KI mice. In a model of peritoneal carcinomatosis and dissemination (by intra-peritoneal injection of YTN16), EMILIN-1 mutant animals also had higher histopathologic scores for invasion;
The use of the MNU protocol, that represents an interesting approach to investigate how deficiency of the ECM molecule EMILIN-1 may affect the incidence and frequency of tumour development, further showed that KO mice had higher tumour incidence, bigger adenomas and lower survival after MNU treatment. Similar results were obtained with the E933A KI model.

Conclusion

These results clearly demonstrate that EMILIN-1, exerts a pivotal role in GC onset, progression and dissemination through the involvement of α4/α9β1 integrin. Loss of EMILIN-1 may lead to alterations in the microenvironment able to promote tumorigenesis in the stomach. Our study also provides a novel animal model that, for the first time, targets a component of the gastric tumor microenvironment.

References

(1) Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet Lond Engl. 2020;396:635–48.
(2) Rojas A, Araya P, Gonzalez I, Morales E. Gastric Tumor Microenvironment.Adv Exp Med Biol. 2020;1226:23–35.8
(3) Deng J-Y, Liang H. Clinical significance of lymph node metastasis in gastric cancer. World J Gastroenterol. 2014;20:3967– 75.
(4) Capuano A, Pivetta E, Sartori G, Bosisio G, Favero A, Cover E, et al.Abrogation of EMILIN1-β1 integrin interaction promotes experimental colitis and colon carcinogenesis.Matrix Biol J Int Soc Matrix Biol. 2019;83:97–115.
(5) Capuano A, Pivetta E, Baldissera F, Bosisio G, Wassermann B, Bucciotti F, et al.Integrin binding site within the gC1q domain orchestrates EMILIN-1-induced lymphangiogenesis. Matrix Biol J Int Soc Matrix Biol. 2019;81:34–49.
(6) Danussi C, Petrucco A, Wassermann B, Pivetta E, Modica TM, Del Bel Belluz L, et al.EMILIN1-α4/α9 integrin interaction inhibits dermal fibroblast and keratinocyte proliferation. JCell Biol. 2011;195:131–45.
(7) Yamamoto M, Nomura S, Hosoi A, Nagaoka K, Iino T, Yasuda T, Saito T, Matsushita H, Uchida E, et al. Established gastric cancer cell lines transplantable into C57BL/6 mice show fibroblast growth factor receptor 4 promotion of tumor growth. Cancer Sci. 2018 May;109(5):1480-1492