Papers by Kazuhiro Yoshida
Molecular and clinical oncology, 2015
In 2006, the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) demonstrated that S-... more In 2006, the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) demonstrated that S-1 is an effective adjuvant therapy for gastric cancer. Following that study, S-1 has been used as the standard adjuvant therapy for gastric cancer in Japan. However, the 1-year completion rate was only 65.8% in the ACTS-GC study and feasibility remains a critical issue. We conducted a study to evaluate the feasibility of 2 weekly administration regimens of S-1 as adjuvant chemotherapy in gastric cancer. The criteria for eligibility included histologically proven stage II (excluding T1), IIIA or IIIB gastric cancer with D2 lymph-node dissection. The patients were randomly assigned to either arm A (S-1 administration for 4 weeks followed by 2 weeks of rest) or arm B (S-1 administration for 2 weeks followed by 1 week of rest). In each arm, treatment was continued for 12 months unless recurrence or severe adverse events were observed. The primary endpoint was feasibility (protocol treatment ...
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Indian Journal of Surgical Oncology, 2021
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International Journal of Molecular Sciences, 2020
Cancer-associated adipocytes are known to cause inflammation, leading to cancer progression and m... more Cancer-associated adipocytes are known to cause inflammation, leading to cancer progression and metastasis. The clinicopathological and transcriptomic data from 2256 patients with breast cancer were obtained based on three cohorts: The Cancer Genome Atlas (TCGA), GSE25066, and a study by Yau et al. For the current study, we defined the adipocyte, which is calculated by utilizing a computational algorithm, xCell, as “intratumoral adipocyte”. These intratumoral adipocytes appropriately reflected mature adipocytes in a bulk tumor. The amount of intratumoral adipocytes demonstrated no relationship with survival. Intratumoral adipocyte-high tumors significantly enriched for metastasis and inflammation-related gene sets and are associated with a favorable tumor immune microenvironment, especially in the ER+/HER2- subtype. On the other hand, intratumoral adipocyte-low tumors significantly enriched for cell cycle and cell proliferation-related gene sets. Correspondingly, intratumoral adipoc...
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Cells, 2021
The colon adenoma–carcinoma sequence is a multistep genomic-altering process that occurs during c... more The colon adenoma–carcinoma sequence is a multistep genomic-altering process that occurs during colorectal cancer (CRC) carcinogenesis. Organoids are now commonly used to model both non-cancerous and cancerous tissue. This study aims to investigate how well organoids mimic tissues in the adenoma–carcinoma sequence by comparing their transcriptomes. A total of 234 tissue samples (48 adenomas and 186 CRC) and 60 organoid samples (15 adenomas and 45 CRC) were analyzed. We found that cell-proliferation-related gene sets were consistently enriched in both CRC tissues and organoids compared to adenoma tissues and organoids by gene set enrichment analysis (GSEA). None of the known pathways in the colon adenoma–carcinoma sequence were consistently enriched in CRC organoids. There was no enrichment of the tumor microenvironment-related gene sets in CRC organoids. CRC tissues enriched immune-response-related gene sets, whereas CRC organoids did not. The proportions of infiltrating immune cell...
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Journal of Clinical Medicine, 2020
Cancer-related microRNAs (miRNAs) are emerging as non-invasive biomarkers for colorectal cancer (... more Cancer-related microRNAs (miRNAs) are emerging as non-invasive biomarkers for colorectal cancer (CRC). This study aimed to analyze the correlation between the levels of tissue and plasma miRNAs and clinicopathological characteristics and surgical resection. This study was a prospective study of CRC patients who underwent surgery. Forty-four sample pairs of tissue and plasma were analyzed. The miRNA levels were evaluated by RT-qPCR. The level of tumor tissue MIR92a showed a significant difference in CRC with lymph node metastasis, stage ≥ III, and high lymphatic invasion. In preoperative plasma, there were significant differences in CRC with stage ≥ III (MIR29a) and perineural invasion (MIR21). In multivariate analysis of lymphatic invasion, the levels of both preoperative plasma MIR29a and tumor tissue MIR92a showed significant differences. Furthermore, in cases with higher plasma miRNA level, the levels of plasma MIRs21 and 29a were significantly decreased after the operation. In t...
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International Journal of Molecular Sciences, 2020
microRNA-143 (miR-143) is a well-known tumor suppressive microRNA that exhibits anti-tumoral func... more microRNA-143 (miR-143) is a well-known tumor suppressive microRNA that exhibits anti-tumoral function by targeting KRAS signaling pathways in various malignancies. We hypothesized that miR-143 suppresses breast cancer progression by targeting KRAS and its effector molecules. We further hypothesized that high expression of miR-143 is associated with a favorable tumor immune microenvironment of estrogen receptor (ER)-positive breast cancer patients which result in improved survival. Two major publicly available breast cancer cohorts; The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used. The miR-143 high expression group was associated with increased infiltration of anti-cancer immune cells and decreased pro-cancer immune cells, as well as enrichment of the genes relating to T helper (Th1) cells resulting in improved overall survival (OS) in ER-positive breast cancer patients. To the best of our knowledge, this is the firs...
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International Journal of Molecular Sciences, 2020
Most breast cancer (BC) patients succumb to metastatic disease. MiR-34a is a well-known tumor sup... more Most breast cancer (BC) patients succumb to metastatic disease. MiR-34a is a well-known tumor suppressive microRNA which exerts its anti-cancer functions by playing a role in p53, apoptosis induction, and epithelial-mesenchymal transition (EMT) suppression. Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) cohorts were used to test our hypothesis that miR-34a high BCs translate to less aggressive cancer biology and better survival in large cohorts. There was no association between miR-34a expression levels and clinicopathological features of BC patients except for HER2 positivity. MiR-34a high expressing tumors were associated with lower Nottingham pathological grades and lower MKI67 expression. In agreement, high miR-34a tumors demonstrated lower GSVA scores of cell cycle and cell proliferation-related gene sets. High miR-34a tumors enriched the p53 pathway and apoptosis gene sets. Unexpectedly, high miR-34a tumors also assoc...
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European Journal of Cancer, 2020
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Annals of Gastroenterological Surgery, 2018
The 11th edition of the Japanese Classification of Esophageal Cancer (EC) was published in 2017. ... more The 11th edition of the Japanese Classification of Esophageal Cancer (EC) was published in 2017. Some correction was made in the depth of tumor invasion to be consistent with the TNM classification by the Union for International Cancer Control (UICC). With regard to surgery, short‐term safety and long‐term effectiveness under thoracotomy/video‐assisted thoracoscopic surgery are expected to be proven by the Japan Clinical Oncology Group (JCOG)1409 study. Results of nutritional management and countermeasures for adverse events not only during the perioperative period but also during EC chemotherapy were reported. From now on, the pursuit of low invasiveness and radicality is desired. Esophageal surgery is also expected to be safe at all institutions. To determine the optimal modality of preoperative treatment and a novel chemo(radio)therapy regimen for patients with distant metastasis, the results of the ongoing JCOG1109 and 0807 studies are being released. The effect of the addition ...
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Gastric Cancer, 2018
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Surgical case reports, 2016
The appropriate therapy for metastatic breast cancer must be selected based on the immunohistoche... more The appropriate therapy for metastatic breast cancer must be selected based on the immunohistochemical phenotype of the cancer. However, biopsy for metastatic lesions is difficult. We herein report a patient with incidental appendicitis caused by a metastatic breast cancer which was successfully treated with effective therapy chosen based on the pathological diagnosis obtained on resection. The patient was a 56-year-old female with right breast cancer and an immunohistochemical status of estrogen receptor (ER) (+), progesterone receptor (PgR) (+), human epidermal growth factor receptor 2 (HER2) (3+), and Ki67 40 %. She received epirubicin and cyclophosphamide therapy followed by docetaxel and trastuzumab, and total mastectomy with axillary dissection was performed. Thereafter, she received postmastectomy radiation, adjuvant trastuzumab, and adjuvant hormone therapy with letrozole. One year and 8 months after the operation, she developed right hydronephrosis and swollen para-aortic l...
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Translational gastroenterology and hepatology, 2016
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Journal of Cancer, 2016
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Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, Jan 7, 2015
Conversion therapy for gastric cancer (GC) has been the subject of much recent attention. It is d... more Conversion therapy for gastric cancer (GC) has been the subject of much recent attention. It is defined as a surgical treatment aiming at an R0 resection after chemotherapy for tumors that were originally unresectable or marginally resectable for technical and/or oncological reasons. However, the indications for resection remain to be clarified. In the present review, we focus on the biology and heterogeneous characteristics of stage IV GC and propose new categories of classification. Stage IV GC patients can be divided based on the absence (categories 1 and 2) or presence (categories 3 and 4) of macroscopically detectable peritoneal dissemination, which has a different biological outcome compared to hematological metastasis. Category 1 is defined oncologically as stage IV but the metastasis is technically resectable. Category 2 includes a marginally resectable metastasis or patients for whom the operation would not necessarily be the best choice. Category 3 includes a potentially u...
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Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2015
The Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) demonstrated a survival benef... more The Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) demonstrated a survival benefit by adjuvant S-1 monotherapy in patients who had undergone curative resection of stage II/III gastric cancer, but there is still a need to improve the efficacy of treatment of stage III disease. We investigated the tolerability and safety of S-1 and oxaliplatin as adjuvant chemotherapy for stage III gastric cancer. Japanese patients with stage III gastric cancer who had undergone D2 or more extensive lymphadenectomy were enrolled. In the first cycle, S-1 (40-60 mg/m(2) twice daily) alone was given orally for 2 weeks of a 3-week cycle. From the second cycle, S-1 was administered as in the first cycle and oxaliplatin (100 mg/m(2)) was infused intravenously on day 1. Treatment was continued for 8 cycles. The primary end point was the treatment completion rate for eight cycles. Sixty-three patients were enrolled and 62 patients were included in analysis. The treatment completion rate was 7...
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PloS one, 2015
We examined the pathobiological properties of beclin-1, which is a key regulator of autophagosome... more We examined the pathobiological properties of beclin-1, which is a key regulator of autophagosome formation in invasive ductal carcinoma of the breast, with a particular focus on the cancer microenvironment. Immunohistochemistry demonstrated that cancer cells and stromal mesenchymal cells expressed beclin-1 in 68 and 38 of 115 invasive ductal cancers, respectively. Expression of beclin-1 in cancer or stromal cells alone did not correlate with patient prognosis. In contrast, loss of beclin-1 in cancer cells and overexpression in stromal mesenchymal cells was associated with local cancer recurrence, postoperative lymph node metastasis, and a poor disease-free survival rate. A comprehensive gene expression analysis was performed on a co-culture of breast cancer cells and mesenchymal stromal cells, that latter of which either expressed beclin-1 or was depleted of beclin-1 by siRNA. Notably, siRNA-mediated downregulation of beclin-1 in mesenchymal cells co-cultured with breast cancer cel...
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Anticancer research, 2010
A comparison was made between pancreatic ductal adenocarcinoma (PDAC), pancreatic intraepithelial... more A comparison was made between pancreatic ductal adenocarcinoma (PDAC), pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous carcinoma (IPMC) in order to understand the association between several markers and malignant potential. Fifteen surgically resected PDACs and four IPMCs were subjected to immunohistochemistry with primary antibodies to Ki-67, p53, MUC2, Gli-1, and Claudin-18 (CLDN18). Ki-67, P53, MUC2, Gli-1 and CLDN18 were positive in 6 (50%), 10 (66.6%), 0 (0%), 4 (26.6%), and 6 (40%) of the 15 PDACs, respectively. Low- to high-grade PanIN complexes were found in 2 out of the 15 PDACs. Gli-1 was continuously expressed in low- and high-grade PanINs. CLDN18 was specifically expressed in high-grade PanINs, whereas the corresponding invasive tubules did not express CLDN18. P53 was positively stained in one of the 4 IPMCs in which minimally invasive tubular type carcinomas were observed. Ki-67 and CLDN18 were positively stained in all 4 IPMCs. CLDN18 wa...
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Hiroshima journal of medical sciences, 2005
The aim of this retrospective study was to evaluate the effectiveness of low-dose cisplatin and 5... more The aim of this retrospective study was to evaluate the effectiveness of low-dose cisplatin and 5-fluorouracil (low-dose FP) as an adjuvant chemoradiotherapy for resected advanced squamous cell carcinoma of the esophagus. From 1994 to 1999, 57 patients who showed an invasion of the tumor over the muscularis propria (T2-T4), regional lymph node metastasis (N1), and no distant metastasis (M0) were enrolled in this analysis. Postoperative chemoradiotherapy (CRT group) was performed on 14 of the patients, and they were compared to the patients who underwent surgery alone (S group) using the matched pair algorithm. In the CRT group, chemotherapy of low-dose FP was combined with concurrent radiotherapy after the esophagectomy. A side-effect of severe dysphagia (NCI-CTC Grade 3) was observed in 4 patients (28.6%) and leukocytopenia in 1 patient (7.1%) among the CRT group. The overall survival rate of the CRT group and matched S group were 35.7% and 28.5% at 5 years, respectively, with no s...
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Molecular Pathology, 1995
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International Journal of Cancer, 2005
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Papers by Kazuhiro Yoshida