Mitsuo Saito

Showa University, Shinagawa, Tōkyō, Japan

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Publications (54)73.65 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A 69-year-old man was diagnosed with advanced esophageal cancer(well-differentiated squamous cell carcinoma). Neoadjuvant chemotherapy consisting of nedaplatin and 5-fluorouracil(5-FU)was initiated. After two courses of chemotherapy, the patient was judged to have achieved a clinical complete response. The patient then decided against undergoing surgery and opted instead to continue with the chemotherapy, receiving five courses in total. However, the esophageal cancer recurred, and subtotal esophagectomy was performed in January 2011. Squamous cell carcinoma with an adenocarcinoma component, which consisted of poorly differentiated squamous cell carcinoma and tubular adenocarcinoma cells, was observed at the primary site. Metastasis of the cancer to the liver was detected 2 months after surgery. The subsequent administration of four courses of docetaxel to the patient did not result in any beneficial effects, and the patient developed carcinomatous pleurisy and died of this complication in November 2011. The patient survived for a total of 21 months after starting chemotherapy. In this case, the chemotherapy itself may have resulted in the dedifferentiation of a welldifferentiated squamous cell carcinoma to result in a poorly differentiated squamous cell carcinoma with an adenocarcinoma component.
    Gan to kagaku ryoho. Cancer & chemotherapy 07/2014; 41(7):909-12.
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    ABSTRACT: For the purpose of detection of colorectal cancers, we tried to detect p16 methylation in the serum of colorectal cancer patients using quantitative methylation-specific polymerase chain reaction (qMSP). Out of 211 serum samples derived from colorectal cancer patients, 14 (7%) exhibited p16 methylation in their serum DNA by qMSP. After completion of qMSP analysis in all specimens, clinicopathological data were correlated with the molecular analysis. Interestingly, a significant difference was observed in the presence of distant metastasis (P = 0.0420). Moreover, a trend was shown toward preferentially developing lymph node metastasis (P = 0.0547), thus suggesting that p16 methylation in serum could be detected more frequently in metastatic colorectal cancer patients. High sensitivity of qMSP makes it possible to detect smaller amounts of tumor DNA in the serum. In principle, the methylation status of a primary tumor is not required in advance to detect circulating tumor DNA, suggesting that qMSP can be used as a screening method for cancer.
    Hepato-gastroenterology 03/2014; 61(130):354-6. · 0.77 Impact Factor
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    ABSTRACT: Background/Aims: Recently, it has been reported that HACE1, the E3 ubiquitin ligase, is epigenetically inactivated in human Wilms' tumors and HACE 1 expression was also down-regulated in colorectal and gastric carcinomas. Methodology: In this study, methylation status of the HACE1 gene was examined in primary carcinomas and the corresponding normal tissues derived from 27 patients with HCC using quantitative methylation-specific PCR (qMSP). Results: Methylation of the HACE1 gene was detected in 18 out of the 27 (67%) HCCs, suggesting that the methylation of HACE1 was frequently observed in HCC. The clinicopathological data were then correlated with these results. In the value of serum AFP (α-fetoprotein), a significant difference was observed (p=0.0025). Conclusions: All stages of HCCs presented HACE1 methylation, indicating that the HACE1 gene has been methylated from the early stages of HCCs.
    Hepato-gastroenterology 06/2013; 60(124):781-3. · 0.77 Impact Factor
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    ABSTRACT: Background/Aims: Recently, we detected that UNC5C expression was downregulated in colon and gastric cancer. Methodology: In the present study, the methylation status of the UNC5C gene was examined in primary carcinomas and the corresponding normal tissues derived from 42 patients with HCC. Results: Methylation of the UNC5C gene was detected in 11 out of the 42 (26%) HCCs, suggesting that the methylation of UNC5C was frequently observed in HCCs. The clinicopathological data were correlated with the methylation results. Conclusions: TNM stage 1 HCC presented UNC5C methylation, indicating that the UNC5C gene has been methylated from the early stages of HCC.
    Hepato-gastroenterology 11/2012; 59(120):2573-5. · 0.77 Impact Factor
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    ABSTRACT: Background/Aims: Recently, it has been reported that WNT5A methylation was frequently detected in colorectal cancers. However, the relationship between the WNT5A methylation and the characteristics of gastric cancer remains unknown. Methodology: Methylation status of the WNT5A gene was examined in primary carcinomas and the corresponding normal tissues derived from 38 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. Results: Aberrant methylation of the WNT5A gene was detected in 7 out of the 38 (18%) primary gastric carcinomas, suggesting that the methylation of WNT5A is observed in gastric carcinomas as well as colorectal ones. The clinicopathological data were correlated with the methylation results. A significant difference was observed in the extent of tumor (p=0.0226). Moreover, a trend was shown towards early TNM stages in methylated tumors (p=0.209). Conclusions: WNT5A was more frequently methylated in early gastric carcinomas.
    Hepato-gastroenterology 11/2012; 59(120):2661-3. · 0.77 Impact Factor
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    ABSTRACT: Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare disease, and many cases are either benign neoplasms or low-graded malignancies; however, a few cases show rapid progressive clinical courses. No effective therapy has yet been established for WDPMP, and the molecular basis of WDPMP tumorigenesis has never been reported. This study shows the malignant transformation of WDPMP in a Japanese female patient, who was alive for 54 months after the initial diagnosis by a laparoscopic biopsy. A molecular analysis of single nucleotide polymorphisms (SNPs), which were located in the neurofibromatosis type 2 (NF2) gene, a tumor suppressor gene assigned to chromosome 22q12.3, revealed the loss of heterozygosity (LOH) of the NF2 gene. Furthermore, SNP analyses determined that LOH was observed in the IL17RA (22q11.1), CHECK2 (22q12.1), and SHANK3 (22q13.3) genes, thus suggesting that NF2 loss occurred through 22q deletions or monosomy 22. The LOH of the NF2 gene was observed in an early stage of WDPMP, thus indicating that LOH of the NF2 gene is an early molecular alteration, and NF2 loss is a molecular mechanism associated not only with malignant pleural mesothelioma, but also with WDPMP.
    Cancer Genetics 10/2012; · 1.92 Impact Factor
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    ABSTRACT: Background, For the purpose of colorectal cancer detection, we investigated fibrillin-2 (FBN2) methylation in the serum of colorectal cancer patients using quantitative methylation-specific polymerase chain reaction (qMSP). Out of 78 patients with colorectal cancer, 49 (63%) exhibited methylation of FBN2 in their tumor tissue DNA, suggesting that FBN2 methylation frequently exists in colorectal cancer. We next examined the methylation status of FBN2 in the serum DNA of patients with colorectal cancer. Out of 49 serum samples, four (8%) exhibited FBN2 methylation in their serum DNA by qMSP, suggesting that FBN2 methylation exists in the serum of colorectal cancer patients. After completion of qMSP analysis in all specimens, clinicopathological data were correlated with the molecular analysis findings. Interestingly, methylation of FBN2 was found in the serum DNA of male (p=0.0167) patients, and in those with hepatic metastasis (p<0.0001). The clinical sensitivity of this assay can be potentially improved by incorporating other common genetic targets such as p53 and KRAS. Advances in technology which will permit for rapid detection of an array of specific mutations and methylation would enhance the utility of this approach.
    Anticancer research 10/2012; 32(10):4371-4. · 1.71 Impact Factor
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    ABSTRACT: Predictors of the response of colorectal cancer to chemotherapy remain poorly understood. We analyzed the mRNA expression levels of enzymes related to sensitivity to 5-fluorouracil derivatives in patients with colorectal cancer. Danenberg tumor profile method (DTP) was used in order to measure mRNA expression levels of thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), and thymidine phosphorylase (TYMP) from 180 patients with colorectal cancer. The relations of expression levels with clinicopathological factors and outcomes were studied. Higher TYMS expression was associated with greater age, DPYD expression with greater age, poorer differentiation and low invasion, and TYMP expression with poorer differentiation and lack of peritoneal metastasis. DPYD expression positively correlated with TYMP expression. In patients with stage IV disease, high DPYD or TYMP expression was associated with poor outcomes. mRNA expression of TYMS, DPYD, and TYMP is associated with distinct characteristics and may be useful for predicting survival in patients with stage IV colorectal cancer.
    Anticancer research 05/2012; 32(5):1757-62. · 1.71 Impact Factor
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    ABSTRACT: Recently, the human deafness, autosomal dominant 5 gene, DFNA5, has frequently been detected in cancer tissues. The methylation status of the DFNA5 gene in colorectal cancer was examined and was compared to the clinocopathological findings. Eighty-five tumor samples and corresponding normal tissues were obtained from patients with colorectal cancer who underwent surgery at our hospital. The methylation status of the DFNA5 gene in these samples was examined by quantitative methylation-specific PCR (qMSP). Subsequently, the clinicopathological findings were correlated with the methylation status of the DFNA5 gene. DFNA5 gene methylation was found in 29 (34%) out of the 85 colorectal carcinomas, suggesting that it was frequently observed in colorectal cancer. A significant correlation with methylation was observed for lymphatic vessel invasion and TNM stage (p=0.0268 and p=0.0189, respectively). DFNA5 might act as a tumor suppressor gene and DFNA5 gene methylation might play an important role in the development of colorectal cancer. Our data implicate DFNA5 gene methylation as a novel molecular biomarker in colorectal cancer.
    Anticancer research 04/2012; 32(4):1319-22. · 1.71 Impact Factor
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    ABSTRACT: In our previous study, we used quantitative methylation-specific polymerase chain reaction (qMSP) to examine the methylation status of tissue factor pathway inhibitor 2 (TFPI2) in the preoperative serum DNA of 215 colorectal cancer patients and found that TFPI2 was methylated in serum DNA from 39 of these patients. In this study, we examined postoperative serum DNA, obtained within one month after surgery from 38 out of the 39 patients and found that TFPI2 was methylated in the serum DNA of only 18 (47%) of these patients, suggesting that TFPI2 methylation in the serum of the remaining colorectal cancer patients was abolished by surgical tumor reduction. Next, we examined the correlation between the presence of TFPI2 methylation in postoperative serum DNA and residual cancer status after surgery. If R0 (no residual cancer) operations were successfully performed, TFPI2 methylation was not detected in postoperative serum. However, if R2 (obvious residual cancer) operations were performed, 17 (77%) out of 22 postoperative sera, still exhibited TFPI2 methylation. Taken together, our results confirm that detection of methylated TFPI2 in serum DNA was derived from colorectal cancer and could serve as a marker of surgical outcome.
    Anticancer research 03/2012; 32(3):787-90. · 1.71 Impact Factor
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    ABSTRACT: Methylation of tissue factor pathway inhibitor-2 (TFPI2) has been detected in the stool of colorectal cancer patients. Using quantitative methylation-specific polymerase chain reaction (qMSP), 39 out of 215 (18%) patients exhibited TFPI2 methylation in their serum DNA, suggesting that a significant number of methylated TFPI2 existed in colorectal cancer patients' sera. Methylation status of the TFPI2 gene was examined in sera derived from 73 patients with gastric cancer using qMSP and the correlation between the methylation status and the clinicopathological findings was evaluated. Out of 73 serum samples, 7 (10%) exhibited TFPI2 methylation in their serum DNA by qMSP, suggesting that TFPI2 methylation existed in the serum of gastric cancer patients. After completion of qMSP analysis of all specimens, clinicopathological data were correlated with the molecular analysis. TFPI2 methylation was significantly more frequently found in serum of patients with lymph node metastasis (p=0.0040) and distant metastasis (p=0.0115). In principle, knowledge of the methylation status of a primary tumor is not required in advance in order to be able to detect circulating tumor DNA. Therefore, qMSP could be used as a cancer screening method.
    Anticancer research 11/2011; 31(11):3835-8. · 1.71 Impact Factor
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    ABSTRACT: Recently, we have reported an important role of epidermal growth factor-like domain 8 (EGFL8) in the progression of colorectal cancer (CRC) and documented EGFL8 to be a novel prognostic biomarker for this malignancy. However, the function of EGFL8 in the other human gastroenterological malignancies such as gastric cancer remains largely unknown. EGFL8 expression in 53 cases of gastric cancer and the corresponding normal tissues were determined by quantitative real-time PCR and the EGFL8 down-regulation score for each patient was calculated. Subsequently, the correlations between EGFL8 down-regulation score and the clinicopathological features of gastric cancer were evaluated. EGFL8 expression was significantly lower in the gastric cancer tissues than the corresponding normal tissues (p=0.0001) and the down-regulation of EGFL8 was evident in 73.6% (39/53) of the gastric carcinomas. More importantly, EGFL8 down-regulation was correlated significantly with peritoneal dissemination (p=0.037) and high TNM stage (p=0.025) of gastric cancer. The down-regulation of EGFL8 might be a novel biomarker for advanced gastric cancer.
    Anticancer research 10/2011; 31(10):3377-80. · 1.71 Impact Factor
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    ABSTRACT: Homeodomein only protein x (HOPX) gene methylation has frequently been detected in cancer tissues. The methylation status of the HOPX gene in colorectal cancer was examined and compared to the clinocopathological findings. Eighty-nine tumor samples and corresponding normal tissues were obtained from colorectal cancer patients who underwent surgery at our hospital. The methylation status of the HOPX gene in these samples was examined by quantitative methylation-specific PCR (qMSP). Subsequently, the clinicopathological findings were correlated with the methylation status of the HOPX gene. HOPX gene methylation was found in 46 (52%) out of the 89 colorectal carcinomas, suggesting that it was frequently observed in colorectal cancer. A significant increase of methylation was observed in the poorly differentiated carcinomas (p=0.0049). HOPX gene methylation could play an important role for the development of colorectal cancer and is closely related to the histological type.
    Anticancer research 09/2011; 31(9):2889-92. · 1.71 Impact Factor
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    ABSTRACT: We examined whether TFPI2 methylation can be used as a molecular marker for colorectal cancers by detecting TFPI2 methylation in colorectal cancer patients' sera by using quantitative methylation-specific polymerase chain reaction (qMSP). The qMSP analysis showed that 39 of 215 (18%) patients exhibited TFPI2 methylation in their serum DNA, suggesting that TFPI2 methylation frequently existed in colorectal cancer patients' sera. After completion of qMSP analysis, clinicopathological data were correlated with molecular data. TFPI2 methylation was significant in the sera of patients with large (p = 0.0022), poorly differentiated carcinoma (p = 0.0164), deep invasion (p = 0.0002), lymph node metastasis (p = 0.0147), or distant metastasis (p < 0.0001). Moreover, TFPI2 methylation was observed more frequently according to the progression of TNM stage, suggesting that serum TFPI2 methylation could be detected more easily in patients with advanced colorectal cancer. We also examined whether serum TFPI2 methylation would be useful in the detection of colorectal cancer, compared to the conventional tumor markers. Detection rates of colorectal cancer using the tumor markers TFPI2 methylation, CEA and CA19-9, in the serum were 18%, 33%, and 17%, respectively. In cases where we combined all three markers, the detection rate was 42%. High sensitivity of qMSP enables detection of smaller amounts of serum tumor DNA. In principle, the methylation status of a primary tumor is not required in advance to detect circulating tumor DNA, suggesting the potential of qMSP as a cancer screening method.
    Cancer letters 07/2011; 311(1):96-100. · 4.86 Impact Factor
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    ABSTRACT: A 55-year-old woman was found to have a type-4 lesion centered on the greater curvature of the lower portion of her stomach during an upper gastrointestinal endoscopic examination.A diagnosis of inoperable advanced gastric carcinoma [type 4, tub 2/por, T3 (SE), N3, H0, P1, cStage IV], complicated by pyloric stenosis, liver dysfunction, and obstructive jaundice untreatable by bile drainage, was made.After obtaining the informed consent of the patient and her family and explain- ing that under the circumstances surgery was not indicated, chemotherapy [S-1 (granules) 80 mg/m2, CDDP 60 mg/m2] was selected. After starting treatment, an improvement in liver dysfunction and jaundice was observed, and at the start of the second course, the patient had become capable of oral feeding.The patient was discharged after completion of the second course. No choices associated with evidence exist for treatment of patients with inoperable advanced gastric cancer (complicated by obstructive jaundice), who are not elderly and have good performance status (PS).We report this case in which improvement of activity of daily living (ADL) was achieved relatively safely by treatment with S-1/CDDP, together with a brief discussion based on the literature.
    Gan to kagaku ryoho. Cancer & chemotherapy 07/2011; 38(7):1197-200.
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    ABSTRACT: In a previous study, we reported a critical role of epidermal growth factor-like domain 7 (EGFL7) in the metastasis of hepatocellular carcinoma (HCC) and documented it to be a prognostic biomarker as well as a potential therapeutic target for HCC. However, the role of EGFL8, the only known paralog of EGFL7, in human malignancies is currently unclear. EGFL8 expression in 101 cases of colorectal cancer (CRC) patients was determined by quantitative reverse transcription-polymerase chain reaction and the clinicopathological features of the CRC patients were correlated with the EGFL8 down-regulation scores. In addition, the survival curve and Cox regression model were also employed to assess the prognostic value of EGFL8 down-regulation. EGFL8 was significantly decreased in CRC tissues (p<0.0001) and the down-regulation of EGFL8 was evidenced in 74.3% (75/101) of the CRC patients. EGFL8 down-regulation correlated significantly to distant metastasis (p=0.038) and high TNM stage (p=0.012) of CRC. The CRC patients with high EGFL8 down-regulation showed either poorer disease-free survival (p=0.0167) or poorer overall survival (p=0.0310) than those with low EGFL8 down-regulation. Multivariable analysis identified EGFL8 down-regulation as an independent prognostic factor for CRC patients (hazard ratio, 12.974; p=0.037). The reduced expression of EGFL8 is closely related to metastastic potential and poor prognosis of CRC, suggesting the down-regulation of EGFL8 as a novel prognostic biomarker for CRC patients.
    Anticancer research 06/2011; 31(6):2249-54. · 1.71 Impact Factor
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    ABSTRACT: Recently, it was shown that the Vimentin gene, usually activated in mesenchymal cells, was highly methylated in colorectal carcinoma. The methylation status of the Vimentin gene was examined in primary carcinomas and the corresponding normal tissues derived from 43 patients with hepatocellular carcinoma (HCC) using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. Aberrant methylation of the Vimentin gene was detected in 24 out of the 43 (56%) primary HCC. This result suggested that the aberrant methylation of the Vimentin gene was frequent in HCC. Subsequently, clinicopathological data were correlated with the methylation status. A significant difference was observed in the value of alpha-fetoprotein (AFP) (p=0.045), maximal tumor size (p=0.048) and TNM stage (p=0.043) between the methylation-positive and -negative cases. Aberrant methylation of Vimetin might be an early event in the course of hepatocarcinogenesis.
    Anticancer research 04/2011; 31(4):1289-91. · 1.71 Impact Factor
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    ABSTRACT: Recently, it has been reported that oncostatin M receptor-β (OSMR) is frequently methylated in primary colon cancer tissues, but not in normal tissues. We examined the methylation status of the OSMR gene in primary carcinomas and the corresponding normal tissues derived from 56 patients with colorectal cancer. The methylation status of the OSMR gene was examined in primary carcinomas and corresponding normal tissues derived from 56 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP), and the correlation between the methylation status and the clinicopathological findings was evaluated. Methylation of the OSMR gene was detected in 18 out of the 56 (32%) primary colon carcinomas. The clinicopathological data were then compared with the methylation results. A significant difference was observed in regard to the extent of tumour (p=0.0442). These results indicated that OSMR was more frequently methylated in non-invasive colorectal carcinomas. OSMR may act as a tumour suppressor in colorectal carcinoma and OSMR methylation may play an important role in non-invasive colorectal cancer.
    Anticancer research 04/2011; 31(4):1293-5. · 1.71 Impact Factor
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    ABSTRACT: Recently, metastasis associated with colon cancer 1 (MACC1) gene was identified by genome-wide search for differentially expressed genes in human colon cancer tissues and metastases. Previously, MACC1 expression was examined in colorectal carcinomas and gastric carcinomas and was found to show significant correlation with peritoneal dissemination. In this study, MACC1 expression was analyzed in 60 samples (tumor and the surrounding non-tumorous liver tissue) collected from 30 patients with hepatocellular carcinoma (HCC) using quantitative real-time polymerase chain reaction (QRT-PCR). Results. MACC1 expression score (tumor:normal) in primary HCC was between 0.01 and 4.59 (average±SD=0.68±0.94). Subsequently, clinicopathological data were correlated with the MACC1 expression. It was found that MACC1 expression showed significant correlation with vascular invasion and α-fetoprotein level (p=0.034, p=0.0098, respectively). These results suggest that MACC1 is more frequently expressed in vascular invasive HCC and may serve as a new parameter for the prognostic prediction of HCC.
    Anticancer research 03/2011; 31(3):777-80. · 1.71 Impact Factor
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    ABSTRACT: The Mus81 gene encodes a critical endonuclease involved in DNA repair and tumor suppression. Our previous study has shown reduced expression of Mus81 in hepatocellular carcinoma and its association with the metastatic potential and prognosis of hepatocellular carcinoma. However, the role of Mus81 in colorectal carcinoma is currently unknown. We therefore carried out the present study to explore the correlation between Mus81 expression and the progression of colorectal carcinoma. Mus81 expression in 92 cases of colorectal carcinoma and matched normal tissues was determined by quantitative real-time polymerase chain reaction. Our results showed that Mus81 expression in colorectal carcinoma tissues was significantly reduced compared with the corresponding normal tissues (P < 0.001) and the downregulation of Mus81 (decreased by more than 50%) was found in 60.9% (56/92) of colorectal carcinoma. Moreover, Mus81 downregulation correlated significantly to hepatic metastasis (P = 0.019) and a high TNM stage (P = 0.025) of colorectal carcinoma. In addition, the decrease of Mus81 was also detected in 10 cases of hepatic metastasis tissues compared with the corresponding primary colorectal carcinoma tissues (P = 0.016). More importantly, colorectal carcinoma patients with apparent Mus81 downregulation have shown significantly poorer overall survival than those with little Mus81 downregulation (P = 0.0374). Also, multivariable Cox regression analysis identified Mus81 downregulation as an independent prognostic factor for colorectal carcinoma (hazard ratio, 1.678; P = 0.040). In conclusion, the reduced expression of Mus81 is closely related to hepatic metastasis and poor prognosis of colorectal carcinoma, indicating Mus81 as a novel prognostic marker for colorectal carcinoma.
    Cancer Science 02/2011; 102(2):472-7. · 3.48 Impact Factor

Publication Stats

272 Citations
73.65 Total Impact Points

Institutions

  • 2009–2012
    • Showa University
      • • Department of General and Gastroenterological Surgery
      • • Department of Surgery
      Shinagawa, Tōkyō, Japan
  • 2011
    • University of Jinan (Jinan, China)
      Chi-nan-shih, Shandong Sheng, China
  • 2010–2011
    • Jinan University (Guangzhou, China)
      Shengcheng, Guangdong, China