Publications by authors named "Yuzo Harada"

5 Publications

  • Page 1 of 1

Clinical significance of CD8 and FoxP3 tumor-infiltrating lymphocytes and MFG-E8 expression in lower rectal cancer with preoperative chemoradiotherapy.

Mol Clin Oncol 2021 May 5;14(5):87. Epub 2021 Mar 5.

Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

Preoperative chemoradiotherapy (CRT) for rectal cancer contributes to tumor down-staging and decreases locoregional recurrence. However, each patient shows a significantly different response to CRT. Therefore, the identification of predictive factors to CRT response would be beneficial to avoid unnecessary treatment. Cancer immunity in patients has been suggested to play an important role in the eradication of the tumor by CRT. In the present study, the utility of CD8 and forkhead box P3 (FoxP3) tumor-infiltrating lymphocytes (TILs) and the expression of a novel immuno-regulatory factor, lactadherin (MFG-E8), in predicting CRT effectiveness in patients with rectal cancer was examined. A total of 61 patients with rectal cancer, who underwent curative resection following CRT were included in the study. The numbers of CD8 and FoxP3 TILs in a biopsy taken before CRT and MFG-E8 expression level in the specimens obtained at the time of the surgery after CRT were examined using immunohistochemical staining, and their association with clinicopathological characteristics, including patient survival, was determined. The tumors with more CD8 TILs in the biopsy samples before CRT showed a significantly more favorable CRT response. The patients with tumors and a higher number of CD8 TILs before CRT also exhibited significantly longer disease-free and overall survival times. Higher MFG-E8 expression level in post-CRT specimens was significantly associated with favorable CRT response; however, no significant association was found with any other clinicopathological characteristics, including survival time. The number of CD8 TILs before CRT was a valuable predictor for CRT response and was associated with favorable prognosis in patients with lower rectal cancer and who were treated with CRT. High MFG-E8 expression level after CRT was also associated with a favorable CRT response.
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http://dx.doi.org/10.3892/mco.2021.2249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976375PMC
May 2021

Prognostic impact of doublecortin-like kinase 1 expression in locally advanced rectal cancer treated with preoperative chemoradiotherapy.

APMIS 2018 Jun;126(6):486-493

Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Preoperative chemoradiotherapy (CRT) is a standard therapy for locally advanced rectal cancer; however, the response varies depending on cases. Therefore, CRT-response predictors need to be elucidated. Cancer stem cells (CSCs), comprising a small part of tumors, are associated with tumor progression and recurrence due to their self-renewal and proliferation abilities. Doublecortin-like kinase 1 (DCLK1) is one of the several putative CSC markers; however, the clinical impact of its expression in rectal cancer has not been evaluated. The aim of this study was to clarify the clinical impact of DCLK1 expression in rectal cancer. We immunohistochemically evaluated DCLK1 expression in surgical specimens of 106 rectal cancer patients, including those who underwent preoperative CRT. The correlations between DCLK1 expression, and clinicopathological features and patient prognosis were then assessed. In rectal cancer patients treated with preoperative CRT, DCLK1 expression was significantly correlated with lymph node metastasis (p = 0.02) and poor cancer-specific survival (p = 0.049). However, in patients treated without preoperative therapy, no such correlation was found. DCLK1 expression can be associated with lymph node metastasis and poor cancer-specific survival in rectal cancer patients who receive CRT.
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http://dx.doi.org/10.1111/apm.12852DOI Listing
June 2018

Leucine-rich repeat-containing G protein-coupled receptor 5 and CD133 expression is associated with tumor progression and resistance to preoperative chemoradiotherapy in low rectal cancer.

Oncol Lett 2017 Dec 18;14(6):7791-7798. Epub 2017 Oct 18.

Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan.

Preoperative chemoradiotherapy has been performed as a standard therapy for advanced low rectal cancer. Cancer stem cells (CSCs) have been reported to contribute to resistance to treatment and patient prognosis. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) and cluster of differentiation (CD133) are putative markers for CSCs. However, their prognostic ability remains unknown, and evaluation of a single marker can be insufficient due to the heterogeneity of cancer. LGR5 and CD133 expression was immunohistochemically evaluated in surgical specimens of 56 patients who received curative resection following chemoradiotherapy for advanced low rectal cancer. In addition, the correlations between their expression levels, and clinicopathological features and patient prognosis were asessed. LGR5 expression was significantly correlated with lymphatic invasion, lymph node metastasis, and tumor node metastasic (TNM) stage. CD133 expression was significantly correlated with vascular invasion and the tumor regression grade. Combined expression was significantly correlated with lymphatic invasion, tumor regression grade and TNM stage, but not with overall, and disease-free survival. LGR5 and CD133 expressions may represent useful markers associated with tumor progression and resistance to chemoradiotherapy in patients with low rectal cancer. Furthermore, combined expression of these markers may be a more useful marker compared with the expression of each single marker.
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http://dx.doi.org/10.3892/ol.2017.7207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727605PMC
December 2017

CD133 Expression at the Metastatic Site Predicts Patients' Outcome in Colorectal Cancer with Synchronous Liver Metastasis.

Ann Surg Oncol 2016 06 29;23(6):1916-23. Epub 2016 Jan 29.

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Background: CD133 is a transmembrane protein that is proposed to be a stem cell marker of colorectal cancer (CRC); however, the correlation between CD133 expression and survival of CRC patients with liver metastasis has not been fully examined.

Methods: CD133 expression was evaluated immunohistochemically, both in primary tumors and synchronous liver metastases of 88 consecutive CRC patients, as well as recurrent lesions in the remnant liver of 27 of these 88 patients. The relationship between CD133 expression and clinicopathological characteristics, recurrence-free survival, and overall survival (OS) was analyzed.

Results: CD133 expression in liver metastases (mCD133) was detected in 50 of 88 patients (56.8 %), and had significant correlation with CD133 expression in primary lesions (pCD133) (p < 0.001). CD133 expression in liver recurrent lesions (recCD133) also had a significant correlation with mCD133 (p < 0.001). mCD133+ patients had significantly longer disease-free survival (p = 0.043) and OS (p = 0.014) than mCD133- patients. In addition, mCD133+ patients had a significantly lower rate of extrahepatic recurrence (p < 0.001).

Conclusions: Patients without CD133 expression in liver metastasis had significantly shorter survival, perhaps because mCD133- patients had a significantly higher rate of extrahepatic recurrence.
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http://dx.doi.org/10.1245/s10434-016-5099-1DOI Listing
June 2016

Intraoperative identification of bile duct perforation following ERCP using indocyanine green-fluorescence imaging.

Dig Dis Sci 2014 May 22;59(5):1063-5. Epub 2013 Dec 22.

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan,

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http://dx.doi.org/10.1007/s10620-013-2982-5DOI Listing
May 2014
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