Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

Hirokazu Taniguchi



Author of

  • +

    P1.03 - Chemotherapy/Targeted Therapy (ID 689)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
    • +

      P1.03-015 - The Relationship between the UGT1A1*27 and UGT1A1*7 Genetic Polymorphisms and Irinotecan-Related Toxicities in Patients with Lung Cancer (ID 7500)

      09:30 - 09:30  |  Author(s): Hirokazu Taniguchi

      • Abstract

      Background:
      Genetic polymorphisms in the UDP-glucuronosyltransferase 1A1 (UGT1A1), UGT1A7, and UGT1A9 genes are associated with interindividual differences in irinotecan toxicities. Purpose: To evaluate the effects of gene polymorphisms, including UGT1A1*7, *27, and *29, on the safety of irinotecan therapy.

      Method:
      The eligibility criteria were as follows: lung cancer patients who were scheduled to undergo irinotecan therapy, aged ≥20 years, and had a performance status of 0-2. After informed consent had been obtained, patients were enrolled, and their blood was collected and used to examine the frequency of the UGT1A1*6, *7, *27, *28, and *29 polymorphisms and the drug concentrations of irinotecan, SN-38, and SN-38G after irinotecan therapy.

      Result:
      Thirty-one patients were enrolled. The patients’ characteristics were as follows: male/female = 25/6, median age (range) = 71 (55-84), stage IIB/IIIA/IIIB/IV = 2/6/11/12, and Ad/Sq/Sm/Oth = 14/10/3/4. The -/-, *6/-, *7/-, *27/-, *28/-, and *29/- UGT1A1 gene polymorphisms were observed in 10 (32%), 10 (32%), 2 (6%), 2 (6%), 7 (23%), and 0 (0%) cases, respectively. There were no homozygous or complex heterozygous polymorphisms. The UGT1A1*27 polymorphism occurred separately from the UGT1A1*28 polymorphism. The lowest leukocyte counts of the patients with the UGT1A1*27 and UGT1A1*6 gene polymorphisms were lower than those seen in the wild-type patients. SN-38 tended to remain in the blood for a prolonged period after the infusion of irinotecan in patients with the UGT1A1*27 or UGT1A1*28 polymorphism. No severe myelotoxicity was seen in the patients with UGT1A1*7.

      Conclusion:
      UGT1A1*27 and UGT1A1*7 are both rare gene polymorphisms. UGT1A1*27 can occur separately from UGT1A1*28 in some circumstances and is related to leukopenia during irinotecan treatment. UGT1A1*7 is less relevant to irinotecan-induced toxicities, and UGT1A1*29 seems to have little clinical impact.

  • +

    P2.07 - Immunology and Immunotherapy (ID 708)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
    • +

      P2.07-045 - A Retrospective Analysis of Nivolumab-Related Pneumonitis in Non-Small Cell Lung Cancer Patients (ID 10051)

      09:30 - 09:30  |  Author(s): Hirokazu Taniguchi

      • Abstract

      Background:
      Nivolumab is a human IgG4 monoclonal antibody that targets programmed cell death-1 (PD-1). In advanced non-small-cell lung cancer patients, nivolumab has been well tolerated. However, some patients develop nivolumab-related pneumonitis.

      Method:
      We retrospectively analyzed the clinical features and prognosis of nivolumab-related pneumonitis in non-small cell lung cancer patients in the institutions of the Nagasaki Thoracic Oncology Group.

      Result:
      From January 1, 2016 to May 31, 2017, 101 non-small cell lung cancer patients were treated with nivolumab monotherapy and 8 patients (7.9%) developed nivolumab-related pneumonitis. 7 were male, and 1 was female, with a median age of 70 years. The histological subtype was squamous cell carcinoma in 3 patients, non-squamous cell carcinoma in 5 patients. 6 patients were stage III or IV. 2 patients were postoperative recurrence. Radiographic pattern was cryptogenic organizing pneumonia (COP) in 6 patients and acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) in 2 patients. The median time from nivolumab treatment initiation to development of pneumonitis was 8.5 weeks (range, 1-16). 2 patients of AIP/ARDS pattern developed pneumonitis within 2 weeks. Bronchoalveolar lavage conducted in 4 patients and bronchoalveolar lavage fluid revealed elevation of lymphocyte in all patients. All patients received corticosteroids. 6 patients of COP pattern had clinical and radiographic improvement. 2 patients of AIP/ARDS pattern worsened clinically and died during the course of pneumonitis treatment. One of patient experienced recurrent pneumonitis in the course of corticosteroid taper.

      Conclusion:
      We retrospectively analyzed the clinical features and prognosis of nivolumab-related pneumonitis in non-small cell lung cancer patients. Nivolumab-related pneumonitis showed variable onset and radiographic patterns. COP pattern was most common. Most patients were successfully treated with corticosteroids, but AIP/ARDS pattern was risk of poor prognosis.

  • +

    P3.03 - Chemotherapy/Targeted Therapy (ID 719)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
    • +

      P3.03-002 - Histone Deacetylase Inhibition Enhances the Antitumor Activity of a MEK Inhibitor in Lung Cancer Cells Harboring RAS Mutations (ID 7917)

      09:30 - 09:30  |  Author(s): Hirokazu Taniguchi

      • Abstract

      Background:
      Non-small-cell lung cancer (NSCLC) can be identified by precise molecular subsets based on genomic alterations that drive tumorigenesis and include mutations in EGFR, KRAS, and various ALK fusions. However, despite effective treatment for EGFR and ALK, promising therapeutics have not been developed for patients with KRAS mutations. Therefore, novel therapeutic strategies for KRAS mutated cancer based on molecular mechanisms are needed to improve their prognosis. It has been reported that one way the RAS-ERK pathway contributes to tumorigenesis is by affecting stability and localization of FOXO3a protein, an important regulator of cell death and the cell cycle.

      Method:
      We used NSCLC cells with RAS mutation to evaluate the effect of a MEK inhibitor in combination with a HDAC inhibitor through the expression and localization of FOXO proteins in vitro and in vivo. Protein expression was examined by Western blotting.

      Result:
      Combined treatment with a MEK inhibitor and a HDAC inhibitor showed synergistic effects on cell viability of RAS mutated lung cancer cells through activation of FOXOs, with a subsequent increase in BIM and cell cycle inhibitors. Moreover, in a mouse xenograft model, the combination of belinostat and trametinib significantly decreases tumor formation through FOXOs by increasing BIM and increase in cell cycle inhibitors p21 and p27.

      Conclusion:
      These findings demonstrate that FOXOs might be one of the critical pathways in RAS driven lung cancer cells, suggesting that the dual molecular targeted therapy for MEK and HDACs may be promising as novel therapeutic strategy in NSCLC with specific populations of RAS mutations.

  • +

    P3.15 - SCLC/Neuroendocrine Tumors (ID 731)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
    • +

      P3.15-001 - The Impact of MET Inhibition on Small-Cell Lung Cancer Cells Exhibiting Aberrant Activation of the HGF/MET Pathway (ID 7898)

      09:30 - 09:30  |  Presenting Author(s): Hirokazu Taniguchi

      • Abstract

      Background:
      Small-cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers, and is characterized as being extremely aggressive, often displaying rapid tumor growth and multiple organ metastases. In addition, the clinical outcome of SCLC patients is poor due to early relapse and acquired resistance to standard chemotherapy treatments. Several molecular targeted therapies were evaluated in SCLC; however, they failed to improve the clinical outcome. The receptor tyrosine kinase MET is a receptor for hepatocyte growth factor (HGF). Although aberrant activation of HGF/MET signaling is known as one of the crucial mechanisms enabling cancer progression and invasion, the mechanisms in SCLC have not been elucidated clearly. The aim of the present study was to evaluate the effect of inhibiting the HGF/MET pathway on tumor progression in SCLC with multi-organ metastasis.

      Method:
      We used eight human SCLC cell lines to elucidate the effect of MET inhibition on tumor progression. MET inhibitors, crizotinib and golvatinib, were used in this study in vitro and in vivo.

      Result:
      We found that the HGF/MET signaling was aberrantly activated in chemo-resistant or chemo-relapsed SCLC cell lines (SBC-5, DMS273, and DMS273-G3H) by the secretion of HGF and/or MET copy number gain. HGF/MET inhibition, induced either by MET inhibitors (crizotinib and golvatinib), or by siRNA-mediated knockdown of HGF or MET, constrained growth of these SCLC cells via the inhibition of ERK and AKT signals. We also revealed that treatment with either crizotinib or golvatinib in vivo suppressed the systemic metastasis of SBC-5 cell tumors in NK cell-depleted SCID mice, predominantly via cell cycle arrest.

      Conclusion:
      These findings reveal that the therapeutic potential of targeting the HGF/MET pathway for inhibition, to constrain tumor progression of SCLC cells exhibiting aberrant activation of HGF/MET signaling. We suggest that it would be clinically valuable to further investigate HGF/MET-mediated signaling in SCLC cells.