Hiroki Hashida

Tazuke Kofukai Medical Research Institute, Kitano Hospital, Ōsaka, Ōsaka, Japan

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Publications (28)232.74 Total impact

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    ABSTRACT: The patient was a 38-year-old woman who visited our hospital complaining of nausea and abdominal pain. A colonoscopy revealed an advanced cancer in the sigmoid colon. A computed tomography(CT)scan showed left hydronephrosis and lymph node metastasis to the left iliopsoas muscle and left ureter. No distant metastasis was found. Since the surgical margins were likely to be positive with a one-stage resection, 3cycles of FOLFOX4(folinic acid, fluorouracil, and oxaliplatin)were administered after creating a transverse loop colostomy. Although the tumor decreased in size, the surgical margins were still suspected to be positive. For further regional tumor control, radiotherapy(1.8 Gy/day for 25 days)to the medial region of the left iliac bone and oral UFT/LV(uracil and tegafur/Leucovorin)were administered. A partial response(PR)was determined in accordance with the Response Evaluation Criteria in Solid Tumors(RECIST). Sigmoidectomy with partial resection of the left ureter was performed by laparotomy. The histologic response was assessed as Grade 2 and all surgical margins were negative. Preoperative chemoradiotherapy may be an effective therapeutic option for locally advanced colon cancer resistant to conventional preoperative chemotherapy.
    No preview · Article · Sep 2014 · Gan to kagaku ryoho. Cancer & chemotherapy
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    ABSTRACT: A 70-year-old female patient underwent pylorus-preserving pancreaticoduodenectomy for carcinoma of the ampulla of Vater in March 2007. In April 2009, multiple lung metastases were detected by CT scanning. The patient was treated with S-1 (80mg/day, day 1-28, followed by 2-weeks withdrawal)from April 2009. The shrinkage of lung metastases was diagnosed as a complete response based on the Response Evaluation Criteria in Solid Tumors(RECIST). No severe toxicities were observed. S-1 is an effective and safe anti-cancer agent available for lung metastases of carcinoma of the ampulla of Vater.
    No preview · Article · Apr 2012 · Gan to kagaku ryoho. Cancer & chemotherapy

  • No preview · Article · Jul 2011 · Cancer Research
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    ABSTRACT: A pancreatic endometrial cyst is an extremely rare disease. Since 1984, only 7 cases have been reported, including the current case. A 35-year-old woman with a history of recurrent severe left upper abdominal pain of 3 months' duration was found to have a cyst in the pancreatic body on the diagnostic imaging findings. With a preoperative diagnosis of mucous cystic adenoma, she underwent a distal pancreatectomy. The histopathological examination of the specimen revealed a pancreatic endometrial cyst. She complained about severe periodic abdominal pain during the convalescence, without any surgical complications. This study reviews previous reports of pancreatic endometrial cysts, and also discusses the clinicopathological features, pathogenesis, and appropriate treatment for this disease.
    No preview · Article · Jul 2011 · Surgery Today
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    ABSTRACT: Metastasis is responsible for most cancer deaths. Here, we show that Aes (or Grg5) gene functions as an endogenous metastasis suppressor. Expression of Aes was decreased in liver metastases compared with primary colon tumors in both mice and humans. Aes inhibited Notch signaling by converting active Rbpj transcription complexes into repression complexes on insoluble nuclear matrix. In tumor cells, Notch signaling was triggered by ligands on adjoining blood vessels, and stimulated transendothelial migration. Genetic depletion of Aes in Apc(Δ716) intestinal polyposis mice caused marked tumor invasion and intravasation that were suppressed by Notch signaling inhibition. These results suggest that inhibition of Notch signaling can be a promising strategy for prevention and treatment of colon cancer metastasis.
    Full-text · Article · Jan 2011 · Cancer cell
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    ABSTRACT: Recent reports have suggested critical roles of myeloid cells in tumor invasion and metastasis, although these findings have not led to therapeutics. Using a mouse model for liver dissemination, we show that mouse and human colon cancer cells secrete CC-chemokine ligands CCL9 and CCL15, respectively, and recruit CD34(+) Gr-1(-) immature myeloid cells (iMCs). They express CCL9/15 receptor CCR1 and produce matrix metalloproteinases MMP2 and MMP9. Lack of the Ccr1, Mmp2, or Mmp9 gene in the host dramatically suppresses outgrowths of disseminated tumors in the liver. Importantly, CCR1 antagonist BL5923 blocks the iMC accumulation and metastatic colonization and significantly prolongs the survival of tumor-bearing mice. These results suggest that CCR1 antagonists can provide antimetastatic therapies for patients with disseminated colon cancer in the liver.
    Preview · Article · Jul 2010 · Proceedings of the National Academy of Sciences
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    ABSTRACT: Neoadjuvant chemotherapy has been a recent focus in the treatment for advanced gastric cancer. Although the preoperative chemotherapeutic regimen of S-1 and CDDP is regarded as effective, safe and well tolerable according to previous clinical study, we experienced a 74-year-old woman who suffered from life-threatening adverse events including severe myelosuppression during the neoadjuvant chemotherapy. Although the patient did not experience any severe adverse events during the first course of treatment, on day 18 of the second course of chemotherapy, she was hospitalized because of anorexia and severe dehydration, leading to following grade 4 leukopenia/neutropenia, bacteremia, and disseminated intravascular coagulation (DIC). She finally recovered from the life-threatening adverse events with intensive therapy and eventually had a distal gastrectomy. Clinicians need to be alert especially to renal dysfunction that induces severe myelosuppression during chemotherapy with S-1, which contains 5-chloro-2,4-dihydroxypyridine (CDHP), a renal excretory inhibitor of dihydropyrimidine dehydrogenase (DPD).
    No preview · Article · Oct 2008 · Gan to kagaku ryoho. Cancer & chemotherapy
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    ABSTRACT: The immediate early response gene X-1 (IEX-1) is a stress-inducible protein that is involved in the regulation of cell proliferation and apoptosis. The aim of this study was to evaluate the prognostic significance of IEX-1 expression in pancreatic cancer. IEX-1 protein expression was examined on paraffin-embedded specimens from 78 patients with pancreatic ductal adenocarcinoma using immunohistochemistry. The relationships between the IEX-1 expression and other clinicopathological parameters and patient survival were evaluated. A similar analysis was conducted in a subgroup of 48 patients, who underwent a macroscopically curative resection with detailed information on the pathological findings. Among 78 pancreatic cancer patients, 41 patients (53%) were positive for IEX-1 staining. In a multivariate analysis, curative operation (P < .001), pathological stage I-III (P = .001), and positive IEX-1 expression (P = .002) were significantly favorable factors for survival. In a subgroup of 48 patients undergoing a macroscopically curative surgery, IEX-1 expression was positive in 28 patients (58%). A significant negative correlation was observed between the IEX-1 expression and serosal (P = .032) or arterial (P = .040) invasion of tumors. A multivariate analysis demonstrated limited local invasion (pT1-3, P = .021), negative lymph node involvement (pN0, P < .001), and positive IEX-1 expression (P = .004) to be significantly favorable factors for survival. The positive IEX-1 expression in tumor tissues may be associated with a better prognosis in pancreatic cancer. An immunohistochemical assessment of IEX-1 expression may therefore be helpful for predicting patient prognosis in this disease.
    No preview · Article · Feb 2008 · Annals of Surgical Oncology
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    ABSTRACT: Inactivation of TGF-beta family signaling is implicated in colorectal tumor progression. Using cis-Apc(+/Delta716) Smad4(+/-) mutant mice (referred to as cis-Apc/Smad4), a model of invasive colorectal cancer in which TGF-beta family signaling is blocked, we show here that a new type of immature myeloid cell (iMC) is recruited from the bone marrow to the tumor invasion front. These CD34(+) iMCs express the matrix metalloproteinases MMP9 and MMP2 and the CC-chemokine receptor 1 (CCR1) and migrate toward the CCR1 ligand CCL9. In adenocarcinomas, expression of CCL9 is increased in the tumor epithelium. By deleting Ccr1 in the background of the cis-Apc/Smad4 mutant, we further show that lack of CCR1 prevents accumulation of CD34(+) iMCs at the invasion front and suppresses tumor invasion. These results indicate that loss of transforming growth factor-beta family signaling in tumor epithelium causes accumulation of iMCs that promote tumor invasion.
    No preview · Article · May 2007 · Nature Genetics

  • No preview · Article · Jan 2007 · Suizo
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    ABSTRACT: CC chemokine receptor 7 (CCR7) plays a critical role in the migration of activated dendritic cells to regional lymph nodes. Recent studies have shown that CCR7 is involved in metastasis in some malignant diseases. The role of CCR7 in esophageal squamous cell carcinoma (SCC) has not yet been clarified. We performed reverse transcription-PCR analysis for CCR7 in 20 esophageal SCC cell lines and immunohistochemical analysis of 96 esophageal SCC samples. We then performed a cell migration assay, F-actin polymerization, and a phagokinetic assay on esophageal SCC cell lines in the presence of CCL21, a ligand of CCR7. CCR7 mRNA was detected in 9 of 20 esophageal SCC cell lines. Immunoreactive CCR7 was found mainly in esophageal cancer cells. High CCR7 expression was significantly correlated with esophageal SCC lymphatic permeation, lymph node metastasis, tumor depth, and tumor-node-metastasis stage and was associated with poor survival. In vitro studies demonstrated that CCL21 significantly increased the cell migration ability of esophageal SCC cell lines, and pseudopodia formation was induced by CCL21 stimulation. Furthermore, CCL21 markedly enhanced the motility of esophageal carcinoma cell lines by the phagokinetic assay. The results suggested that the CCR7/CCL21 receptor ligand system may play a role in the lymph node metastasis of esophageal SCC.
    No preview · Article · Sep 2003 · Clinical Cancer Research
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    ABSTRACT: Cell motility is an important cellular function closely related to the processes of tumour progression and metastasis. Several members of transmembrane 4 superfamily (TM4SF) have been reported to be associated with cell motility and metastatic potential of solid tumour. The aim of this study is to clarify the clinical significance of the member of TM4SF (MRP-1/CD9, KAI1/CD82 and CD151) in human colon cancer. We studied 146 colon cancer patients who underwent curative surgery and studied the expression of MRP-1/CD9, KAI1/CD82 and CD151 using reverse transcriptase - polymerase chain reaction and immunohistochemistry. We found that 64 patients (43.8%) had MRP-1/CD9-positive tumours and that the overall survival rate of patients with MRP-1/CD9-positive tumours was much higher than that of patients with MRP-1/CD9-negative tumours (89.8 vs 50.8%, P<0.001). In contrast, 63 patients (43.2%) had KAI1/CD82-positive tumours and the overall survival rate of patients with KAI1/CD82-positive tumours was also higher than that of patients with KAI1/CD82-negative tumours (84.8 vs 54.9%, P=0.002). On the other hand, positive CD151 expression had a bad effect on the overall survival rate of patients with colon cancer (61.2 vs 74.9%, P=0.022). In a multivariate analysis, MRP-1/CD9 status was a good indicator of the overall survival (P=0.007). We have shown that the reduction of MRP-1/CD9 and KAI1/CD82 expression, and the increasing CD151 expression are indicators for a poor prognosis in patients with colon cancer. This is a first report describing about the relation between CD151 and colon cancer.
    Full-text · Article · Jul 2003 · British Journal of Cancer
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    ABSTRACT: Recently, we established that a murine monoclonal antibody (MAb) MH8-4 inhibits the motility of the colon cancer cell line RPMI4788 and that it recognizes integrin α3. In addition, we have also cloned the motility-related protein-1 (MRP-1)/cluster of differentiation 9 (CD9) as a metastasis suppressor molecule. We investigated integrin α3 expression in 114 resected colon cancers using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to evaluate whether these experimental results are of relevance in the prognosis of actual colon cancers. Furthermore, we investigated the correlation of integrin α3 with MRP-1/CD9 and KAI1/CD82. Sixty patients (52.6%) were evaluated as integrin α3-positive and 54 patients (47.4%) as integrin α3-negative. Integrin α3 expression was associated with tumor status, lymph node status and pathologic stage. The overall and disease-free survival rates for patients whose tumors were positive for integrin α3 were significantly higher than for those with integrin α3-negative tumors (p < 0.001 and p < 0.001, respectively). This same tendency was observed in node-negative patients (p = 0.007 and p = 0.001, respectively). Integrin α3 was found to be the significant prognostic factor in a multivariate analysis using the Cox proportional hazards model (p = 0.036). A correlation was found between integrin α3 with MRP-1/CD9 and KAI1/CD82 for stage I tumors. However, no correlation was found in stage III tumors. Our data seem to suggest that low expression of integrin α3 is a useful indicator of a poor prognosis for colon cancer patients and that colon cancer progresses following collapse of the complex formed by integrin α3 with MRP-1/CD9 and KAI1/CD82. © 2001 Wiley-Liss, Inc.
    Preview · Article · Feb 2002 · International Journal of Cancer
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    ABSTRACT: Recently, we established that a murine monoclonal antibody (MAb) MH8-4 inhibits the motility of the colon cancer cell line RPMI4788 and that it recognizes integrin alpha3. In addition, we have also cloned the motility-related protein-1 (MRP-1)/cluster of differentiation 9 (CD9) as a metastasis suppressor molecule. We investigated integrin alpha3 expression in 114 resected colon cancers using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to evaluate whether these experimental results are of relevance in the prognosis of actual colon cancers. Furthermore, we investigated the correlation of integrin alpha3 with MRP-1/CD9 and KAI1/CD82. Sixty patients (52.6%) were evaluated as integrin alpha3-positive and 54 patients (47.4%) as integrin alpha3-negative. Integrin alpha3 expression was associated with tumor status, lymph node status and pathologic stage. The overall and disease-free survival rates for patients whose tumors were positive for integrin alpha3 were significantly higher than for those with integrin alpha3-negative tumors (p < 0.001 and p < 0.001, respectively). This same tendency was observed in node-negative patients (p = 0.007 and p = 0.001, respectively). Integrin alpha3 was found to be the significant prognostic factor in a multivariate analysis using the Cox proportional hazards model (p = 0.036). A correlation was found between integrin alpha3 with MRP-1/CD9 and KAI1/CD82 for stage I tumors. However, no correlation was found in stage III tumors. Our data seem to suggest that low expression of integrin alpha3 is a useful indicator of a poor prognosis for colon cancer patients and that colon cancer progresses following collapse of the complex formed by integrin alpha3 with MRP-1/CD9 and KAI1/CD82.
    No preview · Article · Feb 2002 · International Journal of Cancer
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    ABSTRACT: The molecular basis of cell motility is highly complex and is controlled by a number of molecular systems, whereas angiogenesis is an important biological component of tumor progression. The aims of this study were to investigate the possible involvement of proteins at the cell surface in controlling cell motility and angiogenesis, and to identify the cell surface molecules involved in gastrointestinal tumors. We addressed these issues using functional monoclonal antibodies, which inhibit cell motility, endothelial cell migration, and tube formation. Furthermore, we investigated the relationship between this antigen and colon cancer, and showed the prognostic significance in human colon cancer. We established a murine monoclonal antibody MH8-11, which inhibits cell motility and in vitro angiogenesis. This epitope was a 165-kilodalton protein, and the sequencing analysis revealed that it was almost identical to aminopeptidase N (APN)/cluster of differentiation (CD) 13. APN/CD13 expression was associated with tumor status (P = 0.025). The disease-free and overall survival rate for patients with positive APN/CD13 expression tumors was significantly lower than that for patients with negative APN/CD13 expression tumors (P = 0.014, 0.033, respectively). Among 47 node-positive patients, the survival rate of patients with negative APN/CD13 expression was better than that of those with positive APN/CD13 expression. Our data suggest that APN/CD13 is involved in cell motility and angiogenesis, and APN/CD13 expression may be a useful indicator of a poor prognosis for node-positive patients with colon cancer.
    No preview · Article · Feb 2002 · Gastroenterology
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    ABSTRACT: Neutral endopeptidase modulates the growth of lung cancer, while aminopeptidase N degrades the extracellular matrix and is involved in cell motility. We studied the metastasis mechanism to detect novel metastasis-associated molecules and to evaluate them for clinical application. We studied the relationship between the expression of neutral endopeptidase and aminopeptidase N by quantitative reverse transcript-polymerase chain reaction analysis in 132 patients with non-small cell lung cancer undergoing radical surgery from 1991 to 1996. Patients with neutral endopeptidase-positive and aminopeptidase N-negative tumors were defined as group A, those with neutral endopeptidase-positive and aminopeptidase N-positive or neutral endopeptidase-negative and aminopeptidase N-negative tumors as group B, and those with neutral endopeptidase-negative and aminopeptidase N-positive tumors as group C. The 5-year survival of group A patients (92.9%) was significantly better than that of group B patients (64.7%) and much better than that of group C patients (38.2%) (P = 0.0011). Neutral endopeptidase and aminopeptidase N thus have statistically significant P in overall survival in Cox regression (P = 0.019). Neutral endopeptidase and aminopeptidase N gene expressions are significant indicators of prognosis.
    No preview · Article · Sep 2001 · The Japanese Journal of Thoracic and Cardiovascular Surgery

  • No preview · Article · Apr 2001 · Gastroenterology

  • No preview · Article · Apr 2001 · Gastroenterology
  • H Hashida · A Takabayashi · M Adachi · T Imai · K Kondo · N Kohno · Y Yamaoka · M Miyake
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    ABSTRACT: The molecular basis of cell motility is obviously highly complex and is considered to be controlled by a number of molecular systems including cell adhesion molecules, their receptors, cytoskeletal components, a junctional unit connecting cytoskeletal components and membrane receptors, and various peptide growth factors. The possible involvement of proteins at the cell surface in controlling cell motility has been systematically investigated. Previously, we have addressed this question using functional monoclonal antibodies (MAbs), which inhibit cell motility as probes. In order to further identify cell surface molecules involved in metastasis of gastrointestinal tumors, the present study utilized an approach based on the selection of a colon cancer cell line RPMI4788, which showed high motility out of a large number of human gastrointestinal tumor cell lines. MAb MH8-4 was established after immunization of mice with RPMI4788 and selected on the basis of inhibition of RPMI4788 cell migration in a transwell penetration assay. MH8-4 inhibited the phagokinetic tract motility of various cancer cell lines. A cDNA cloning revealed that MH8-4 recognized a specific protein structure, integrin alpha 3. In order to determine whether these experimental results are of relevance with respect to actual human gastrointestinal tumors, we investigated integrin alpha 3 expression in 40 colon cancers with distant metastases. Our immunohistochemical study showed that in almost 27.5% of the cases, the metastatic tumors had lower integrin alpha 3 levels than their corresponding primary tumors. Moreover, there were no primary tumors with lower integrin alpha 3 expression than their corresponding metastatic tumors. Our data suggest that low integrin alpha 3 expression may be associated with the metastatic potential of certain colon cancers.
    No preview · Article · Feb 2001 · International Journal of Oncology
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    ABSTRACT: Previously we showed that MRP-1/CD9 might prevent tumor metastasis by suppression of cell motility and invasion of tissue barriers. The present study explored the possibility of preventing metastasis of mouse melanoma BL6 by expression of MRP-1/CD9 through gene transfer. A replication-deficient adenovirus vector was used for the in vivo transfer of MRP-1/CD9 cDNA. Intratumor injection of an adenovirus vector (rAd-MRP-1/CD9) expressing MRP-1/CD9 resulted in a 73.7% reduction in the number of pulmonary metastases of mice and the median survival time of mice treated with rAd-MRP-1/CD9 was significantly longer than those treated with the rAd-beta-gal vector (103.2 approximately plus;8.5 days vs 71.2 approximately plus;5.2 days, P<0.001 respectively). These results support the expression of MRP-1/CD9 through gene transfer as a therapeutic strategy for preventing metastases and prolonging survival, and support the feasibility of gene transfer in a clinically relevant setting.
    Preview · Article · Nov 2000 · Oncogene

Publication Stats

1k Citations
232.74 Total Impact Points

Institutions

  • 1998-2011
    • Tazuke Kofukai Medical Research Institute, Kitano Hospital
      Ōsaka, Ōsaka, Japan
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
  • 2000-2001
    • Kyoto University
      Kioto, Kyōto, Japan
  • 1996
    • The University of Tokyo
      • Department of Neurology
      Edo, Tōkyō, Japan