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Article: Investigating the Role of Tumor-Infiltrating Lymphocytes as Predictors of Lymph Node Metastasis in Deep Submucosal Invasive Colorectal Cancer: A Retrospective Cross-Sectional Study.

Tamari, Hirosato / Kitadai, Yasuhiko / Takigawa, Hidehiko / Yuge, Ryo / Urabe, Yuji / Shimamoto, Fumio / Oka, Shiro

2023 Volume 15, Issue 21

Abstract: The role of tumor-infiltrating T cells (TILs) in colorectal cancer (CRC) and their significance in early-stage CRC remain unknown. We investigated the role of TILs in early-stage CRC, particularly in deep submucosal invasive (T1b) CRC. Sixty patients ... ...

Abstract	The role of tumor-infiltrating T cells (TILs) in colorectal cancer (CRC) and their significance in early-stage CRC remain unknown. We investigated the role of TILs in early-stage CRC, particularly in deep submucosal invasive (T1b) CRC. Sixty patients with CRC (20 each with intramucosal [IM group], submucosal invasive [SM group], and advanced cancer [AD group]) were randomly selected. We examined changes in TILs with tumor invasion and the relationship between TILs and LN metastasis risk. Eighty-four patients with T1b CRC who underwent initial surgical resection with LN dissection or additional surgical resection with LN dissection after endoscopic resection were then selected. TIL phenotype and number were evaluated using triple immunofluorescence for CD4, CD8, and Foxp3. All subtypes were more numerous according to the degree of CRC invasion and more abundant at the invasive front of the tumor (IF) than in the center of the tumor (CT) in the SM and AD groups. The increased Foxp3 cells at the IF and high ratios of Foxp3/CD4 and Foxp3/CD8 positively correlated with LN metastasis. In conclusion, tumor invasion positively correlated with the number of TILs in CRC. The number and ratio of Foxp3 cells at the IF may predict LN metastasis in T1b CRC.
Language	English
Publishing date	2023-10-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15215238
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Article ; Online: Sodium bicarbonate ingestion mitigates the heat-induced hyperventilation and reduction in cerebral blood velocity during exercise in the heat.

Katagiri, Akira / Kitadai, Yasuhiko / Miura, Akira / Fukuba, Yoshiyuki / Fujii, Naoto / Nishiyasu, Takeshi / Tsuji, Bun

Journal of applied physiology (Bethesda, Md. : 1985)

2021 Volume 131, Issue 5, Page(s) 1617–1628

Abstract: Hyperthermia during exercise in the heat causes minute ventilation ([Formula: see text]) to increase, which leads to reductions in arterial ... ...

Abstract	Hyperthermia during exercise in the heat causes minute ventilation ([Formula: see text]) to increase, which leads to reductions in arterial CO
MeSH term(s)	Eating ; Exercise ; Hot Temperature ; Humans ; Hyperventilation ; Male ; Sodium Bicarbonate/pharmacology
Chemical Substances	Sodium Bicarbonate (8MDF5V39QO)
Language	English
Publishing date	2021-09-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	219139-8
ISSN	1522-1601 ; 0021-8987 ; 0161-7567 ; 8750-7587
ISSN (online)	1522-1601
ISSN	0021-8987 ; 0161-7567 ; 8750-7587
DOI	10.1152/japplphysiol.00261.2021
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Article: Comprehensive Analysis of Gene Expression Profiling to Explore Predictive Markers for Eradication Therapy Efficacy against

Takigawa, Hidehiko / Yuge, Ryo / Miyamoto, Ryo / Otani, Rina / Kadota, Hiroki / Hiyama, Yuichi / Hayashi, Ryohei / Urabe, Yuji / Sentani, Kazuhiro / Oue, Naohide / Kitadai, Yasuhiko / Oka, Shiro / Tanaka, Shinji

Cancers

2023 Volume 15, Issue 4

Abstract: Although radiotherapy is the standard treatment ... ...

Abstract	Although radiotherapy is the standard treatment for
Language	English
Publishing date	2023-02-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15041206
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Article ; Online: Angiogenesis and lymphangiogenesis of gastric cancer.

Kitadai, Yasuhiko

Journal of oncology

2010 Volume 2010, Page(s) 468725

Abstract: Tumor angiogenesis is the result of an imbalance between positive and negative angiogenic factors released by tumor and host cells into the microenvironment of the neoplastic tissue. The stroma constitutes a large part of most solid tumors, and cancer- ... ...

Abstract	Tumor angiogenesis is the result of an imbalance between positive and negative angiogenic factors released by tumor and host cells into the microenvironment of the neoplastic tissue. The stroma constitutes a large part of most solid tumors, and cancer-stromal cell interactions contribute functionally to tumor growth and metastasis. Activated fibroblasts and macrophages in tumor stroma play important roles in angiogenesis and tumor progression. In gastric cancer, tumor cells and stromal cells produce various angiogenic factors, including vascular endothelial growth factor, interleukin-8, platelet-derived endothelial cell growth factor, and angiopoietin. In addition, Helicobacter pylori infection increases tumor cell expression of metastasis-related genes including those encoding several angiogenic factors. We review the current understanding of molecular mechanisms involved in angiogenesis and lymphangiogenesis of human gastric cancer.
Language	English
Publishing date	2010-03-29
Publishing country	Egypt
Document type	Journal Article
ZDB-ID	2461349-6
ISSN	1687-8469 ; 1687-8450
ISSN (online)	1687-8469
ISSN	1687-8450
DOI	10.1155/2010/468725
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Article ; Online: Angiogenesis and Lymphangiogenesis of Gastric Cancer

Yasuhiko Kitadai

Journal of Oncology, Vol

2010 Volume 2010

Keywords	Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Language	English
Publishing date	2010-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fatty change of the liver microenvironment influences the metastatic potential of colorectal cancer.

Masaki, Satoshi / Hashimoto, Yoshimi / Kunisho, Shoma / Kimoto, Akiko / Kitadai, Yasuhiko

International journal of experimental pathology

2020 Volume 101, Issue 5, Page(s) 162–170

Abstract: Fatty liver is the most common cause of liver disease, and its prevalence has been increasing globally. Colorectal cancer (CRC) accounts for approximately 10% of all cancers and metastasizes most commonly to the liver. Paget's 'Seed and Soil' theory of ... ...

Abstract	Fatty liver is the most common cause of liver disease, and its prevalence has been increasing globally. Colorectal cancer (CRC) accounts for approximately 10% of all cancers and metastasizes most commonly to the liver. Paget's 'Seed and Soil' theory of metastasis proposed that the secondary growth of cancer cells is dependent on the distal organ microenvironment. This implies that the risk of metastasis may change due to changes in the microenvironment of target organs. However, the association between steatosis, fatty change in the liver microenvironment, and liver metastasis has not been clarified. Here, we induced fatty liver conditions in BALB/c mice using a choline-deficient high-fat diet with 0.1% methionine (CDAHFD) and then injected the CT26 cells to produce experimental metastasis. The number of metastatic tumours was significantly increased in mice with severe fatty liver as compared to control mice. The average size of metastatic tumours was smaller in mice with moderate fatty liver than in control mice. The stromal components, including cancer-associated fibroblasts, tumour-associated macrophages and tumour-infiltrating lymphocytes, were also examined. Metastatic tumours in fatty liver showed invasive growth patterns without a fibrotic capsule. Compared to control groups, the polarization of macrophages and subtypes of tumour-infiltrating lymphocytes differed depending on the extent of fatty liver progression. These results indicated that fatty changes in the liver influenced liver metastasis of CRC. Although moderate fatty changes suppress the growth of metastatic tumours in the liver, a severe fatty microenvironment may promote invasion and metastasis through alteration of the tumour microenvironment (TME).
MeSH term(s)	Animals ; Cell Line, Tumor ; Choline Deficiency ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Fatty Liver/chemically induced ; Fatty Liver/metabolism ; Female ; Humans ; Immunohistochemistry ; Liver/metabolism ; Liver/pathology ; Liver Neoplasms/metabolism ; Liver Neoplasms/secondary ; Macrophages/pathology ; Mice ; Mice, Inbred BALB C ; Tumor Microenvironment
Language	English
Publishing date	2020-08-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1016006-1
ISSN	1365-2613 ; 0958-4625 ; 0007-1021 ; 0959-9673
ISSN (online)	1365-2613
ISSN	0958-4625 ; 0007-1021 ; 0959-9673
DOI	10.1111/iep.12371
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Article: Cancer-stromal cell interaction and tumor angiogenesis in gastric cancer.

Kitadai, Yasuhiko

Cancer microenvironment : official journal of the International Cancer Microenvironment Society

2009 Volume 3, Issue 1, Page(s) 109–116

Abstract: Recent studies in molecular and cellular biology have shown that tumor growth and metastasis are not determined by cancer cells alone but also by a variety of stromal cells. The stroma constitutes a large part of most solid tumors, and cancer-stromal ... ...

Abstract	Recent studies in molecular and cellular biology have shown that tumor growth and metastasis are not determined by cancer cells alone but also by a variety of stromal cells. The stroma constitutes a large part of most solid tumors, and cancer-stromal cell interaction contributes functionally to tumor growth and metastasis. Angiogenesis is the result of an imbalance between positive and negative angiogenic factors released by tumor and host cells into the microenvironment of the neoplastic tissue. In gastric cancer, tumor cells and stromal cells produce various angiogenic factors, including vascular endothelial growth factor, interleukin-8, and platelet-derived endothelial cell growth factor. The microenvironment in the gastric mucosa may also influence the angiogenic phenotype of gastric cancer. Helicobacter pylori infection increases expression of several angiogenic factors by tumor cells. Activated fibroblasts and macrophages in tumor stroma also play an important role in angiogenesis and tumor progression. We review the current understanding of cancer-stromal cell interaction as it pertains to tumor angiogenesis in gastric cancer.
Language	English
Publishing date	2009-12-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2422345-1
ISSN	1875-2284 ; 1875-2292
ISSN (online)	1875-2284
ISSN	1875-2292
DOI	10.1007/s12307-009-0032-9
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Article ; Online: Low-Dose Alcohol-Induced Inhibition of Mouse Orthotopically Transplanted Tumors Is Associated with T-Cell Response.

Kimoto, Akiko / Kunisho, Shoma / Morita, Ryohei / Onishi, Minako / Zhou, Qian / Ono, Atsushi / Miki, Daiki / Shimamoto, Fumio / Kitadai, Yasuhiko

Pathobiology : journal of immunopathology, molecular and cellular biology

2022 Volume 90, Issue 1, Page(s) 22–30

Abstract: Introduction: The effects of low-dose alcohol consumption on colorectal cancer development are not well understood. Epidemiological studies have reported that people who consume small amounts of alcohol have lower mortality rates than both nondrinkers ... ...

Abstract	Introduction: The effects of low-dose alcohol consumption on colorectal cancer development are not well understood. Epidemiological studies have reported that people who consume small amounts of alcohol have lower mortality rates than both nondrinkers and heavy drinkers. This phenomenon has been labeled the "J-curve effect" of alcohol. This study examined the effects of low-dose alcohol (0.5%, 1%, and 2%) on tumor growth in a transplant colon cancer model. Methods: BALB/c and BALB/c nude mice were used to analyze T-cell immunity. Syngeneic CT26 murine colon cancer cells were implanted into the cecal wall, and the resulting T-cell immune effects were monitored. Results: The growth of orthotopic tumors was markedly inhibited upon ingestion of low-dose (0.5%) alcohol compared with that in the control mice. In contrast, cells from the same line were injected into the cecal wall of nude mice, and tumor growth inhibition was not observed. Histopathological and RNA sequence analyses were performed to elucidate the mechanisms underlying tumor growth inhibition. An increase in tumor CD8+ T lymphocytes and changes in cytokine levels were observed. Microbiome analysis using 16S rRNA gene sequencing of cecal contents was performed and revealed Mucispirillum schaedleri and Clostridium cocleatum showed decreased and increased abundance, respectively, in the alcohol group. Discussion/conclusion: Ingesting a threshold amount of alcohol results in the infiltration of T lymphocytes, which may enhance immune responsiveness in mouse colorectal cancer models.
MeSH term(s)	Animals ; Mice ; Mice, Nude ; RNA, Ribosomal, 16S ; Colonic Neoplasms/pathology ; CD8-Positive T-Lymphocytes ; Cytokines ; Ethanol ; Disease Models, Animal ; Mice, Inbred BALB C ; Cell Line, Tumor
Chemical Substances	RNA, Ribosomal, 16S ; Cytokines ; Ethanol (3K9958V90M)
Language	English
Publishing date	2022-05-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1022703-9
ISSN	1423-0291 ; 1015-2008
ISSN (online)	1423-0291
ISSN	1015-2008
DOI	10.1159/000524478
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Article: The Anti-Tumor Effect of the Newly Developed LAT1 Inhibitor JPH203 in Colorectal Carcinoma, According to a Comprehensive Analysis.

Otani, Rina / Takigawa, Hidehiko / Yuge, Ryo / Shimizu, Daisuke / Ariyoshi, Misa / Miyamoto, Ryo / Kadota, Hiroki / Hiyama, Yuichi / Hayashi, Ryohei / Urabe, Yuji / Ishikawa, Akira / Oue, Naohide / Kitadai, Yasuhiko / Oka, Shiro / Tanaka, Shinji

Cancers

2023 Volume 15, Issue 5

Abstract: A novel large neutral amino acid transporter 1 (LAT1)-specific inhibitor, JPH203, is expected to cause cancer-specific starvation and possess anti-tumor effects; however, its anti-tumor mechanism for colorectal cancer (CRC) remains unclear. We analyzed ... ...

Abstract	A novel large neutral amino acid transporter 1 (LAT1)-specific inhibitor, JPH203, is expected to cause cancer-specific starvation and possess anti-tumor effects; however, its anti-tumor mechanism for colorectal cancer (CRC) remains unclear. We analyzed LAT family gene expressions in public databases using UCSC Xena and evaluated LAT1 protein expression using immunohistochemistry in 154 cases of surgically resected CRC. We also evaluated mRNA expression using polymerase chain reaction in 10 CRC cell lines. Furthermore, JPH203 treatment experiments were conducted in vitro and in vivo using an allogeneic immune-responsive mouse model with abundant stroma created via the orthotopic transplantation of the mouse-derived CRC cell line CT26 and mesenchymal stem cells. The treatment experiments were followed by comprehensive gene expression analyses with RNA sequencing. Database analyses and immunohistochemistry research on clinical specimens revealed that LAT1 expression was cancer-dominant, and its increase was accompanied by tumor progression. In vitro, JPH203 was effective in an LAT1 expression-dependent manner. In vivo, JPH203 treatment considerably reduced tumor size and metastasis, and RNA sequencing-based pathway analysis showed that not only tumor growth and amino acid metabolism pathways, but also stromal activation-related pathways were suppressed. The results of the RNA sequencing were validated in the clinical specimens, as well as both in vitro and in vivo. LAT1 expression in CRC plays an important role in tumor progression. JPH203 may inhibit the progression of CRC and tumor stromal activity.
Language	English
Publishing date	2023-02-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15051383
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Article: Indications for Dental Floss Clip Traction During Gastric Endoscopic Submucosal Dissection by Less-Experienced Endoscopists.

Tamari, Hirosato / Oka, Shiro / Kotachi, Takahiro / Teshima, Hajime / Mizuno, Junichi / Fukuhara, Motomitsu / Tanaka, Hidenori / Tsuboi, Akiyoshi / Yamashita, Ken / Yuge, Ryo / Urabe, Yuji / Kitadai, Yasuhiko / Arihiro, Koji / Tanaka, Shinji

Journal of gastric cancer

2023 Volume 23, Issue 4, Page(s) 512–522

Abstract: Purpose: Dental floss clip (DFC) traction-assisted endoscopic submucosal dissection (ESD) is widely performed owing to its simplicity. This study aimed to clarify the appropriate indications for the DFC traction method in early gastric cancer when ESD ... ...

Abstract	Purpose: Dental floss clip (DFC) traction-assisted endoscopic submucosal dissection (ESD) is widely performed owing to its simplicity. This study aimed to clarify the appropriate indications for the DFC traction method in early gastric cancer when ESD is performed by less-experienced endoscopists. Methods and methods: We retrospectively analyzed 1,014 consecutive patients who had undergone gastric ESD performed by less-experienced endoscopists between January 2015 and December 2020. Gastric ESD was performed without DFC in all cases before December 2017 [DFC (-) group, 376 cases], and ESD was performed with DFC in all cases after January 2018 [DFC (+) group, 436 cases]. The procedure time and rates of en bloc resection, complete resection, and adverse events of the groups were compared. Results: The procedure time did not differ significantly between the 2 groups. However, when comparing lesions >20 mm, the procedure time in the DFC (+) group was significantly shorter than that in the DFC (-) group (95±46 vs. 75±31, P<0.01). The procedure time for lesions located in the greater curvature of the upper or middle stomach and lesions >20 mm located in the lesser curvature side of the stomach in the DFC (+) group was significantly shorter than that in the DFC (-) group. Conclusions: The indications for DFC during gastric ESD by less-experienced endoscopists include lesions located in the greater curvature of the upper or middle stomach, and lesions >20 mm located in the lesser curvature of the stomach.
Language	English
Publishing date	2023-11-06
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2637180-7
ISSN	2093-5641 ; 2093-582X
ISSN (online)	2093-5641
ISSN	2093-582X
DOI	10.5230/jgc.2023.23.e37
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