Takamichi Komori

Publications (8)20.24 Total impact

• Article: Prediction of the response to chemotherapy in advanced esophageal cancer by gene expression profiling of biopsy samples.

  Masaaki Motoori, Ichiro Takemasa, Makoto Yamasaki, Takamichi Komori, Atsushi Takeno, Hiroshi Miyata, Shuji Takiguchi, Yoshiyuki Fujiwara, Takushi Yasuda, Masahiko Yano, Nariaki Matsuura, Kenichi Matsubara, Morito Monden, Masaki Mori, Yuichiro Doki
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  ABSTRACT: To improve the prognosis of advanced esophageal cancer, neoadjuvant chemotherapy (NACT) followed by surgery is a promising treatment strategy. NACT has been shown to improve the prognosis of responders. However, non-responders not only suffer from side-effects, but they also lose precious time to take advantage of other possible treatments. Therefore, it is crucial to establish a reliable method that allows prediction of response before chemotherapy. A biopsy sample can provide valuable information on the biological characteristics of an individual esophageal cancer, which can affect chemosensitivity. Comprehensive gene expression profiling (GEP) using oligonucleotide microarray covering 30,000 human probes was performed in 50 pretreatment endoscopic biopsy samples from 25 patients with esophageal squamous cell cancer (ESCC) who underwent cisplatin-based chemotherapy (two samples per patient). Chemotherapeutic responses were evaluated by the reduction rate of the tumor area on CT scans. Responders were defined as patients with reduction rates of ≥50% and non-responders were defined as patients with <50% decrease. The diagnostic system, that predicts responses to chemotherapy, was constructed with the 199 most informative genes, and showed 82% of accuracy. Furthermore, the predictive performance of this system was confirmed using an additional ten samples with an accuracy of 80%. This study shows that GEP of pretreatment ESCC biopsy samples has the potential to predict responses to chemotherapy.
  International Journal of Oncology 11/2010; 37(5):1113-20. · 2.40 Impact Factor
• Article: The feasibility of using biopsy samples from esophageal cancer for comprehensive gene expression profiling.

  Masaaki Motoori, Ichiro Takemasa, Makoto Yamasaki, Takamichi Komori, Atsushi Takeno, Hiroshi Miyata, Shuji Takiguchi, Yoshiyuki Fujiwara, Takushi Yasuda, Masahiko Yano, Nariaki Matsuura, Kenichi Matsubara, Morito Monden, Masaki Mori, Yuichiro Doki
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  ABSTRACT: Advanced esophageal cancer has been recently treated by multimodal therapy including preoperative chemotherapy or chemoradiotherapy and surgery. A biopsy sample provides a valuable specimen for understanding the biological characteristics of individual esophageal cancer. Pretreatment prediction of the response to chemotherapy or radiotherapy based on biological characteristics using biopsy samples is a desirable goal. In using biopsy samples for molecular analysis, there are two problems; the proportion of cancer cells and the intratumor heterogeneity. This study was conducted to investigate the feasibility of using endoscopic biopsy samples of esophageal squamous cell cancer (ESCC) for comprehensive gene expression profiling (GEP). Comprehensive GEP was performed in 40 bulky ESCC specimens and 10 normal esophageal epithelial specimens from patients who underwent esophageal resection and 52 endoscopic ESCC biopsy samples from 26 patients (two samples per one patient). Unsupervised hierarchical cluster analysis showed distinct profiles between the bulky ESCC specimens and normal epithelial specimens. Also, unsupervised hierarchical cluster analysis revealed distinct profiles between the biopsy ESCC samples and normal epithelial specimens. Moreover, a couple of biopsy samples taken from different locations of the same tumor were closely clustered together. That is, biopsy ESCC samples were distinguished from normal esophageal epithelial specimens and the intratumor heterogeneity of GEP was smaller than intertumor heterogeneity. GEP using biopsy ESCC samples is feasible and has the potential to represent the biological properties.
  International Journal of Oncology 09/2009; 35(2):265-71. · 2.40 Impact Factor
• Article: Gene expression of colorectal cancer: preoperative genetic diagnosis using endoscopic biopsies.

  Takamichi Komori, Ichiro Takemasa, Makoto Yamasaki, Masaaki Motoori, Takeshi Kato, Nobuteru Kikkawa, Naomasa Kawaguchi, Masataka Ikeda, Hirofumi Yamamoto, Mitsugu Sekimoto, Kenichi Matsubara, Nariaki Matsuura, Morito Monden
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  ABSTRACT: In colorectal cancer, to predict the response to chemo- and/or radio-therapy or the existence of lymph node metastasis preoperatively, a more competent diagnostic system is required, in addition to conventional diagnosis based on morphology and pathology. The application of gene expression profiling to preoperative cancer diagnosis using endoscopic biopsies could enable the selection of a more appropriate therapy for patients. In this study, we evaluated the feasibility of gene expression profiling using preoperative biopsies of colorectal tumors in a clinical setting, by investigating the influence of intra-tumor heterogeneity on the profiles and testing the prediction ability of tumor malignancy. Under endoscopic examination, two biopsies were sampled from each of 10 colorectal cancers and 10 adenomas, and their gene expression data were obtained using cDNA microarrays. The intra- and inter-tumor heterogeneities of the profiles were compared with unsupervised clustering analysis. Molecular prediction of tumor malignancy using biopsies was performed with the supervised classification algorithm. In clustering analysis, almost all paired biopsies from the same tumors joined each other. Pearson's correlation coefficients of the profiles between biopsies from the same tumors (mean, 0.83) were significantly greater than those of the profiles between biopsies from other cancers (mean, 0.58) (p<0.0001). In the supervised classification method, malignancy was correctly predicted in 39 out of 40 biopsies with 8-71 informative genes. Gene expression profiling using endoscopic biopsies of colorectal tumors revealed that the intra-tumor heterogeneity was smaller than the inter-tumor heterogeneity and tumor malignancy was correctly predicted. Our findings suggest that the technique of gene expression profiling accurately represents the biological properties of colorectal cancer and could help the preoperative diagnosis of this disease.
  International Journal of Oncology 03/2008; 32(2):367-75. · 2.40 Impact Factor
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  Available from: spandidos-publications.com

  Article: The gene expression profile represents the molecular nature of liver metastasis in colorectal cancer.

  Makoto Yamasaki, Ichiro Takemasa, Takamichi Komori, Shouji Watanabe, Mitsugu Sekimoto, Yuichiro Doki, Kenichi Matsubara, Morito Monden
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  ABSTRACT: The major cause of death in colorectal cancer is related to liver metastasis. Although the metastatic process has been well studied, many aspects of the molecular genetic basis of metastasis remain unclear. Elucidation of the molecular nature of liver metastasis is urgent to improve the outcome of colorectal cancer. We analyzed the chronological gene expression profiles of 104 colorectal samples corresponding to oncogenic development including normal mucosa, localized and metastasized primary tumors, and liver metastatic lesions as fundamental samples using a custom cDNA microarray. The gene expression patterns in 104 samples were classified into four groups closely associated with their metastatic status, and the genes of each group appropriately reflected the metastatic process. To investigate the existence of metastatic potential in primary tumors using metastasis-related genes detected by chronological analysis, we performed a hierarchical cluster and supervised classification analysis of 28 independent primary tumors. Hierarchical cluster analysis segregated the tumors according to their final metastatic status, rather than their clinical stages, and the profile of metastasized primary tumors resembled one of a metastatic lesion apart from a primary lesion rather than one of a non-metastasized primary tumor. Using the supervised classification approach, the expression profile of these genes allowed the classification of tumors diagnosed as localized cancer into two classes, the localized and the metastasized class, according to their final metastatic status. The disease-free survival and overall survival were significantly longer in the localized class than the metastasized class. Chronological analysis of the gene expression profile provides a better understanding of the metastatic process. Our results suggest that the metastatic potential is already encoded in the primary tumor and is detectable by a gene expression profile, which allows the prediction of liver metastasis in patients diagnosed with localized tumors and also the design of new strategies for the treatment and diagnosis of colorectal cancer.
  International Journal of Oncology 02/2007; 30(1):129-38. · 2.40 Impact Factor
• Article: Prediction of peritoneal metastasis in advanced gastric cancer by gene expression profiling of the primary site.

  Masaaki Motoori, Ichiro Takemasa, Yuichiro Doki, Sakae Saito, Hiroshi Miyata, Shuji Takiguchi, Yoshiyuki Fujiwara, Takushi Yasuda, Masahiko Yano, Yukinori Kurokawa, Takamichi Komori, Makoto Yamasaki, Noriko Ueno, Shigeyuki Oba, Shin Ishii, Morito Monden, Kikuya Kato
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  ABSTRACT: Peritoneal metastasis is the most common cause of tumour progression in advanced gastric cancer. Clinicopathological findings including cytologic examination of peritoneal lavage have been applied to assess the risk of peritoneal metastasis, but are sometimes inadequate for predicting peritoneal metastasis in individuals. Hence, we tried to construct a new prediction system for peritoneal metastasis by using a PCR-based high throughput array with 2304 genes. The prediction system, constructed from the learning set comprised of 30 patients with the most informative 18 genes, classified each case into a 'good signature group' or 'poor signature group'. Then, we confirmed the predictive performance in an additional validation set comprised of 24 patients, and the prediction accuracy for peritoneal metastasis was 75%. Kaplan-Meier analysis with peritoneal metastasis revealed significant difference between these two groups (P=0.0225). By combining our system with conventional clinicopathological factors, we can identify high risk cases for peritoneal metastasis more accurately.
  European Journal of Cancer 09/2006; 42(12):1897-903. · 5.54 Impact Factor
• Article: Unusual atrophic change after repeated arterial therapy for hepatocellular carcinoma: report of a case.

  Takamichi Komori, Yo Sasaki, Terumasa Yamada, Hiroaki Ohigashi, Osamu Ishikawa, Etsuo Inoue, Shingo Ishiguro, Toshihito Seki, Shingi Imaoka
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  ABSTRACT: We report the case of a 45-year-old man with advanced hepatocellular carcinoma (HCC) who was able to undergo radical surgery after repeated transarterial therapy. Transarterial chemoembolization was repeated three times, and thereafter, transarterial infusion chemotherapy using Lipiodol was performed on the right hepatic artery. Because notable atrophy of the right lobe and compensated hypertrophy of the left lobe were detected after this therapy, an extended right lobectomy could be performed. Histologically, the HCC showed complete necrosis. The remarkable atrophic change of the right lobe was thought to be due to an obstruction of the right portal veins by the spread of inflammation around the bile duct necrosis, in addition to the narrowing of the hepatic artery. A thorough understanding of this phenomenon and the development of methods to clinically apply it in the treatment of cancer patients may thus lead to an increase in the percentage of resectable cases of advanced HCC.
  Surgery Today 02/2004; 34(1):76-9. · 1.22 Impact Factor
• Article: Prognostic significance of the size of cancer nests in metastatic lymph nodes in human esophageal cancers.

  Takamichi Komori, Yuichiro Doki, Toshiyuki Kabuto, Osamu Ishikawa, Masahiro Hiratsuka, Yo Sasaki, Hiroaki Ohigashi, Kohei Murata, Terumasa Yamada, Isao Miyashiro, Masayuki Mano, Shingo Ishiguro, Shingi Imaoka
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  ABSTRACT: Postoperative survival of patients with esophageal cancers after curative surgery is strongly affected by the presence of lymph node metastasis. The number and location of lymph node metastases have been evaluated and graded, but the clinical significance of their size has not been well investigated. Of 322 esophageal cancer patients who underwent curative operations with radical lymph node dissection, 170 (53%) had lymph node metastasis. A total of 784 metastatic lymph nodes were obtained, and the area of the cancer nests was measured microscopically in the cross section. The data from each patient included the area of the largest cancer nest in the positive nodes (Nmax), classified as Na (<4 mm2), Nb (4-25 mm2), Nc (25-100 mm2), or Nd (>100 mm2). The 170 patients were classified according to the Nmax value: Na, 31 (18.2%); Nb, 35 (20.5%); Nc, 49 (28.8%); and Nd, 55 (32.4%). The 5-year survival rate was 77.7% in patients without lymph node metastasis and 35.4% in those with lymph node metastasis. When classified by Nmax, the 5-year survival rate was 77.8% for Na, 63.9% for Nb, 18.8% for Nc, and 12.8% for Nd. There was no significant difference in the survival rate between Na patients and those without lymph node metastasis. Nmax showed significant correlation with the primary tumor size, depth of tumor invasion, and number and location of metastatic lymph nodes, but not with histologic type or primary tumor location. In multivariate analysis, the Nmax value, the number of lymph node metastases and depth of tumor invasion were independent prognostic factors, while the location of the lymph node metastases was not statistically significant. The area of the largest cancer nest in the lymph nodes was one of the most significant prognostic factors for esophageal cancers. This estimation is objective and reproducible and may be of great importance when deciding the therapeutic modality for patients with esophageal cancers.
  Journal of Surgical Oncology 01/2003; 82(1):19-27. · 2.10 Impact Factor
• Article: Invasive ductal adenocarcinoma of the remnant pancreatic body 9 years after resection of an intraductal papillary-mucinous carcinoma of the pancreatic head: a case report and comparison of DNA sequence in K-ras gene mutation.

  Takamichi Komori, Osamu Ishikawa, Hiroaki Ohigashi, Terumasa Yamada, Yo Sasaki, Shingi Imaoka, Akihiko Nakaizumi, Hiroyuki Uehara, Sachiko Tanaka, Yoshiyuki Mano, Tsutomu Kasugai
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  ABSTRACT: Recently, there have been a few case reports of invasive ductal adenocarcinoma (IDC) developed in the remnant pancreas after partial pancreatectomy for intraductal papillary-mucinous neoplasm (IPMN). It is necessary to clarify their histogenetic relationships among two sporadic tumors and their surrounding duct epithelium and it would be more reliable if genetic analysis is added to the conventional histology. We report a 76-year-old woman who received pancreaticoduodenectomy for IPMN with a focal in situ carcinoma (IPMC), which was transitional to the surrounding duct epithelium with papillary proliferation and a wide variety of dysplasia. Nine years after the operation, she died of IDC in the remnant pancreatic body and its surrounding duct epithelium consisted of hyperplastic mucous cells with slight-mild dysplasia. Analysis of K-ras mutation at codon 12 (wild-GGT) by direct sequencing after polymerase chain reaction indicated that their transitioning patterns differed from each other: CGT in IPMC; no mutation in the mildly dysplastic duct epithelium around IPMC; GAT in IDC of the remnant pancreas; and AGT in mucous cell hyperplasia with mild dysplasia close to the IDC. This is the first report in which the DNA sequence of K-ras mutation was determined for the two sporadic pancreatic cancers and surrounding duct changes. The following two suggestions are made: (1) the cell-origin might have differed between the two types of cancer (IDC and IPMC); and (2) no precursor lesion toward IDC or IPMC was identified in their surrounding duct epithelium.
  Japanese Journal of Clinical Oncology 05/2002; 32(4):146-51. · 1.78 Impact Factor