Noriyuki Akita

Shinshu University, Shonai, Nagano, Japan

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Publications (9)32.88 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Oxaliplatin in combination with 5-fluorouuacil and leucovorin (FOLFOX) is one of the most commonly used first-line chemotherapies for patients with advanced or metastatic colorectal cancer. Pulmonary toxicity, including interstitial pneumonia (IP)/peumonitis, is a very rare complication. We report a case of fatal IP associated with FOLFOX therapy in a patient with metastatic rectal cancer. A 74-year-old man with rectal adenocarcinoma and associated liver metastases underwent palliative surgery and 21 cycles of modified FOLFOX6 therapy. After starting the 22nd therapy cycle, the patient developed a high fever with non-productive cough. Chest X-ray demonstrated diffuse ground-glass opacities in both lungs, and computed tomography showed severe disorder of the bilateral lung architecture. On the basis of a lymphocyte stimulation test (DLST), oxaliplatin-induced IP was diagnosed. Intravenous administration of high-dose methylprednisolone was started, but the symptoms and radiological findings were not improved. The patient died of respiratory failure 16days after the last administration of oxaliplatin. Although IP is a rare but potentially fatal complication of oxaliplatin-based treatment in colorectal cancer patients, clinicians should pay careful attention to the clinical respiratory symptoms and radiographic findings in colorectal cancer patients receiving FOLFOX therapy. KeywordsOxaliplatin–Colorectal cancer–Interstitial pneumonia
    Clinical Journal of Gastroenterology 06/2011; 4(3):157-161. DOI:10.1007/s12328-011-0217-x
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    ABSTRACT: Cholangiocarcinoma (CCA) is a common carcinoma of the liver, and the majority of patients with CCA have a poor prognosis due to the lack of effective nonsurgical therapies in addition to its rapid progression and inoperability at the time of diagnosis. The development of novel nonsurgical therapeutics that efficiently target CCA could significantly improve the prognosis for patients presenting with CCA. Here, we describe the iterative production and characterization of a novel peptide, designated COP35 (CCA-binding oligopeptide 35), which binds selectively to human CCA, identified by bacteriophage biopanning using the intrahepatic CCA cell line RBE and the normal cholangiocyte cell line MMNK-1. COP35 was found to augment the growth inhibitory effects of 5-fluorouracil (5-FU) against RBE cells. Utilizing pull-down assay and liquid chromatography, we identify the clathrin heavy chain accompanied by GRP78/BiP as a COP35-binding partner. In summary, we identify COP35 as a possible candidate for peptide-targeted therapies for CCA.
    Molecular Cancer Research 06/2011; 9(6):688-701. DOI:10.1158/1541-7786.MCR-10-0470 · 4.50 Impact Factor
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    ABSTRACT: Anorectal malignant melanoma (AMM) is a relatively rare disease. Because of its poor prognosis, the optimal surgical treatment for AMM is still controversial and difficult to determine. In this paper, we report five cases of AMM that have been treated by surgery and/or other methods at Shinshu University Hospital within the last decade. We also review the present five cases along with 74 other Japanese cases reported between 1997 and 2006 and discuss the role of surgery in the treatment of AMM. Among our AMM patients, two who underwent radical abdominoperineal resection had long survival, while the other three patients who underwent palliative surgery had a poor outcome. On the total of 79 AMM patients, those who underwent curative surgery had a better outcome than those who underwent palliative surgery (p < 0.0001). Furthermore, the outcome of AMM patients at stages 0 and I was better than that of AMM patients at stages II, III, and IV (p < 0.0001). There was no significant difference in survival between AMM patients with and without adjuvant chemotherapy. In conclusion, AMM patients treated by curative surgery can expect long-term survival, although the usefulness of adjuvant chemotherapy for AMM patients is controversial.
    International Journal of Colorectal Disease 12/2008; 23(12):1257-62. DOI:10.1007/s00384-008-0529-6 · 2.42 Impact Factor
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    ABSTRACT: The development of intravascular conjugates that efficiently deliver genes or drugs to tumors is limited by the lack of efficacious targeting ligands. Small targeting peptides, such as those iterated by phage display technology, offer enormous potential for these applications. The majority of reports published to date have focused on the identification of peptides isolated for their ability to bind to human cancer cell lines in vitro, and have failed to account for the loss of polarization and de-differentiation of such cells from their in vivo state. Here, we report a novel approach for the identification of peptides capable of binding specifically to cancer cells derived from clinically resected human colon cancer. In this strategy, laser capture microdissection (LCM) is performed on a surgically resected colon cancer specimen to separate only cancer cells from the specimen. Subsequently, biopanning was performed on the LCM-selected colon cancer cells to identify peptide sequences that bound specifically to them. A peptide containing the SPT motif was selected as the most promising consensus sequence binding specifically to the LCM-selected colon cancer cells. Phage clones displaying the SPT motif demonstrated 9-fold higher binding to colon cancer cells derived from a patient than insertless phage (p < 0.05), while, recovery of the SPT phage from the colon cancer cell lines DLD-1 and HCT-15 was 7-fold higher than that of the control insertless phage (p < 0.05). The binding of SPT phage to colon cancer cells from the patient was confirmed by immunofluorescence. Additionally, a synthesized SPT-containing peptide (SPTKSNS) showed binding activity in the absence of mitogenic effects on colon cancer cells in vitro. In summary, we have introduced LCM into a biopanning procedure and identified a small peptide that binds preferentially to colon cancer cells derived from a clinically resected sample. This procedure could be applicable for the design of customized cancer cell targeting methodologies using clinical biopsy samples from human subjects.
    Journal of Drug Targeting 07/2008; 16(5):396-404. DOI:10.1080/10611860802088796 · 2.72 Impact Factor
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    ABSTRACT: Intravenous targeting of anticancer agents should improve both efficacy and therapeutic index. However, rational design of targeting constructs requires detailed definition of receptor targets and must take account of polarised tissue architecture that may restrict access to chosen receptors from the bloodstream. Bacteriophage biopanning provides a solution to this problem, identifying targeting sequences by functional selection rather than design, although reiterative panning in polarized human tumours has not previously been attempted. Here, we report an ex vivo, intra-arterial method for biopanning in freshly-resected human tumours, enabling reiterative selection of oligopeptide sequences capable of intravascular targeting to human colorectal tumours. Significant consensus was observed after two rounds of panning in tumours from different patients, and lead sequences demonstrated tumour targeting in samples from unrelated patients. This novel approach may be applicable to a wide range of settings, thus enabling iteration of consensus targeting sequences for tumour imaging and selective delivery of anticancer agents.
    Journal of Drug Targeting 06/2007; 15(4):311-9. DOI:10.1080/10611860701195510 · 2.72 Impact Factor
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    ABSTRACT: This is a report of in vivo intraperitoneal biopanning, and we successfully identified a novel peptide to target the multiple peritoneal tumors of gastric cancer. A phage display library was injected directly into the abdominal cavity of mice bearing peritoneal tumors of human gastric cancer, and phages associated with the tumors were subsequently reclaimed from isolated samples. The tumor-associated phages were amplified and the biopanning cycle was repeated five times to enrich for high affinity tumor-selective binding peptides. Finally, a tri-peptide motif, KLP, which showed homology with laminin 5 (a ligand for alpha3beta1 integrin), was identified as a binding peptide for peritoneal tumors of gastric cancer. Phage clones displaying the sequence KLP showed 64-fold higher binding to peritoneal tumors than control phage and were preferentially distributed in tumors rather than in normal organs after intraperitoneal injection into mice. In addition, the KLP phages were more likely to bind to cancer cells in malignant ascites derived from a patient with recurrent gastric cancer. Synthesized peptide containing the motif KLP (SWKLPPS) also showed a strong binding activity to peritoneal tumors without cancer growth effect. Liposomes conjugated with SWKLPPS peptide appeared significantly more often in tumors than control liposomes after intraperitoneal injection into mice. Furthermore, modification of liposomes with SWKLPPS peptide enhanced the antitumor activity of adriamycin on gastric cancer cells. The peptide motif KLP seems a potential targeting ligand for the treatment of peritoneal metastasis of gastric cancer.
    Cancer Science 11/2006; 97(10):1075-81. DOI:10.1111/j.1349-7006.2006.00291.x · 3.48 Impact Factor
  • A. Shimizu · F. Maruta · N. Akita · S. Miwa · S. Miyagawa
    Journal of Hepatology 04/2006; 44. DOI:10.1016/S0168-8278(06)80382-X · 10.40 Impact Factor
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    ABSTRACT: We carried out identification of a small peptide binding to human hepatocellular carcinoma (HCC) cells with the aim of applying the peptide for future HCC-targeted therapy or imaging. The biopanning technique using phage peptide display libraries was performed on HCC cells in vitro, and a phage clone expressing the HCC-binding peptide motif was selected. The binding activity of the selected phage was evaluated by plaque infection assay and immunofluorescence on cell lines. In addition, the binding activity of the peptide-expressing phage was investigated using HCC specimens derived from patients who had undergone hepatectomy for HCC. A heptapetide, Thr-Thr-Pro-Arg-Asp-Ala-Tyr (TTPRDAY), was identified as a motif binding to HCC. TTPRDAY bound specifically to HCC cells in comparison with other cancer cells, and the binding to HCC cells was also confirmed by immunofluorescence. In addition, the synthesized TTPRDAY peptide showed binding activity and a non-mitogenic effect on HCC cells in vitro. TTPRDAY-presenting phage showed more significant binding to HCC cells derived from specimens obtained from actual patients than to non-cancerous liver tissue. The motif TTPRDAY, identified by the biopanning technique, shows significant binding to HCC cells.
    Oncology 02/2006; 71(1-2):136-45. DOI:10.1159/000100479 · 2.61 Impact Factor
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    ABSTRACT: Rice extract has been shown to protect gastric mucosa from stress-induced damage. In this study, the antibiotic effect and the anti-inflammatory effect of orally administered aqueous rice extract on Helicobacter pylori infection and H. pylori-induced gastritis, respectively, in Mongolian gerbils were investigated. Fifty specific-pathogen-free male Mongolian gerbils, seven weeks old, were divided into four groups: uninfected, untreated animals (group A); uninfected, rice extract-treated animals (group B); H. pylori-infected, untreated animals (group C); and H. pylori-infected, rice extract-treated animals (group D). Group C and D animals were killed 12 weeks after H. pylori infection (i.e., at 19 weeks of age) and group A and B animals were also killed at age 19 weeks. The stomachs were removed for histopathological examination with hematoxylin-and-eosin staining and anti-5'-bromo-2'-deoxyuridine (BrdU) immunostaining, and to determine the bacterial burden. Serum anti-H. pylori antibody titers were also tested. In groups A and B, the gastric mucosa showed no inflammatory cell infiltration and a few BrdU-reactive cells. Group C animals developed marked chronic active gastritis in the gastric mucosa, and BrdU-labeled cells in the gastric mucosa markedly increased in number. In group D animals, a significant reduction occurred in the degree of neutrophilic polymorphonuclear cell infiltration into the gastric mucosa, in the BrdU-labeling indices of gastric epithelial cells, and in anti-H. pylori antibody titers in the serum (P < 0.01), compared with although H. pylori was not completely eradicated. The rice extract was effective in suppressing inflammation and epithelial cell proliferation in the gastric mucosa in H. pylori-infected Mongolian gerbils. The rice extract has potential to exhibit a protective effect on H. pylori-related gastric mucosal diseases.
    Journal of Gastroenterology 06/2005; 40(5):459-66. DOI:10.1007/s00535-005-1570-7 · 4.02 Impact Factor