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J. Osugi



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    P1.01 - Poster Session 1 - Cancer Biology (ID 143)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.01-020 - Expression profile of serotonin 2B receptor (HTR2B) in non-small-cell lung cancer (ID 1872)

      09:30 - 16:30  |  Author(s): J. Osugi

      • Abstract

      Background
      Recently developed molecular targeting drugs are highly effective against various cancers, however the duration of response is limited. To overcome this problem, researchers have sought to find the resistance mechanism and identify novel targets. The majority of the drugs are related to receptors tyrosine kinase (RTKs), and recently, G-protein coupled receptor (GPCR) has also been reported to play a critical role in cancer biology. We thus attempted to identify the target GPCR for the treatment of lung cancer cells.

      Methods
      We analyzed 124 patients with non-small-cell-lung cancer who had undergone surgery from January 2008 through November 2011. Expression levels of GPCR mRNA in the tumor tissues and the adjacent normal tissues were examined by comparative genomic analysis. We then sought to find the relationship between clinical features and the GPCRs that showed differential expression levels between the two types of tissues. In addition, we examined the protein levels of the GPCRs by immunohistochemistry.

      Results
      We identified 3 GPCRs and 1 related molecule. Of the 4 molecules, serotonin receptor 2B (HTR2B) was expressed higher in tumor tissues than in normal tissues. HTR2B was expressed statistically higher in the tumor tissues of female, adenocarcinoma, and non-smokers (p=0.012. 0.001, 0.045, respectively), and tended to be expressed higher in patients who harbored EGFR mutation (p=0.086). No statistically significant differences were observed in relapse-free survival. Immunohistochemistry demonstrated that HTR2B was expressed especially in the invasive front of the tumor.

      Conclusion
      Differential expression of HTR2B between cancer cells and normal tissues and its invasive potential suggest that further investigation into this molecule is needed.

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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 2
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      P1.06-024 - FAM83B, a novel molecular target for lung squamous cell carcinoma. (ID 1869)

      09:30 - 16:30  |  Author(s): J. Osugi

      • Abstract

      Background
      Recently, personalize therapy for non-small cell lung cancer (NSCLC) has been improving and significantly to extract various molecular target. However, development of molecular targeted drugs is proceeding only in lung adenocarcinoma to date, while there are few drugs for lung squamous cell carcinoma (SCC). Therefore, we tried to extract molecular targets for SCC by comprehensive gene expression analysis of clinical specimen.

      Methods
      The subjects of this study consisted of 215 patients with NSCLC who underwent complete resection since 2005 to 2011 in our hospital. They included 102 adenocarcinomas and 113 SCC. First, we tried to extract molecules specific to SCC by tissue array analysis of clinical specimen. We selected FAM83B as a candidate marker for SCC by using comprehensive gene expression analysis. Then, we examined the protein expression of FAM83B in NSCLC tissues by immunoblot and immunohistochemical analysis (IHC). The relationship between the FAM83B expression and clinic-pathological factors was statistically analyzed.

      Results
      FAM83B expression at mRNA level was significantly higher in SCC than in normal lung or adenocarcinoma (P<0.0001). Immunoblot analysis also confirmed this tendency. In IHC, FAM83B was diffusely localized in the cytoplasm and/or plasma membrane. When more than 10% positive area for FAM83B were judged as “positive”, 94.3% (107/113) of SCC and 14.7% (15/102), of adenocarcinoma were positive. If the patients were divided into two subgroups by IHC (54 high-expression patients and 53 low-expression patients), high-expression group was associated with a better disease free survival rate (P=0.042, log-rank test). Figure 1

      Conclusion
      Our results indicated that FAM83B could be a reliable diagnostic and prognostic biomarker for SCC. Biological function of FAM83B in lung cancer is not well known. Further analyses should be required to identify its clinical significance and biological function.

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      P1.06-029 - Serum nitric oxide could be a predictor for the response of bevacizumab in patients with non-small cell lung cancer (ID 2198)

      09:30 - 16:30  |  Author(s): J. Osugi

      • Abstract

      Background
      Bevacizumab (BEV), an inhibitory monoclonal antibody to VEGF, is widely used to treat patients with non-small cell lung cancer (NSCLC), but biomarkers that predict BEV response are controversial. Reportedly, hypertension is linked to response to BEV therapy, possibly because BEV might suppress vascular nitric oxide (NO) production. However, the usefulness of serum NO (NO~s~) as a predictive biomarker for BEV therapy has not previously been shown. Here, we studied the predictive value of NO~s~ in BEV-treated patients with NSCLC.

      Methods
      Fifteen patients with advanced or recurrent NSCLC treated with BEV-based regimens were evaluated retrospectively. Blood samples were taken before treatment (Pre), and after the 1st and 2nd chemotherapy courses (Post~1~ and Post~2~, respectively). NO~s~ (NO~2~[–]/NO~3~[–]) was assayed by the Griess method. Relationships between clinical parameters (e.g., clinical responses, adverse events) were analyzed against NO~s~. This study was approved by the ethics committee of Fukushima Medical University.

      Results
      Median Pre NO~s~ was 62.7 ±42.9 μmol/L (range: 1.9–138.8 μmol/L). NO~s~ tended to decrease at Post~1~ (46.6 ± 30.8 μmol/L; P = 0.246) and Post~2~ (37.6 ± 29.4 μmol/L; P = 0.072) compared to Pre values. Post/Pre NO ratios correlated with hypertension onset (Post~1~/Pre: P = 0.316; Post~2~/Pre: P = 0.148) and clinical response (Post~1~/Pre: P = 0.389; Post~2~/Pre: P = 0.163). Decrease at Post~2~ might correlate with progression-free survival (P = 0.127). NOs level of patients with treatment responder increased at Post PD (P = 0.101).

      Conclusion
      NO~s~, could be a predictive biomarker for response to BEV in patients with NSCLC. Prospective confirmation is needed; we are conducting a prospective translational study of NOs in BEV therapy. Figure 1Figure 2