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  • Wiley  (7)
  • Nakano, Noriyuki  (7)
  • 1
    Online Resource
    Online Resource
    In‐depth proteomics reveals the characteristic developmental profiles of early lung adenocarcinoma with epidermal growth factor receptor mutation
    Wiley ; 2023
    In:  Cancer Medicine Vol. 12, No. 9 ( 2023-05), p. 10755-10767
    Details
    In: Cancer Medicine, Wiley, Vol. 12, No. 9 ( 2023-05), p. 10755-10767
    Abstract: Lung adenocarcinoma progresses stepwise from atypical adenomatous hyperplasia to adenocarcinoma in situ (AIS), followed by minimally invasive adenocarcinoma (MIA), and then obvious invasive adenocarcinoma. In this study, we examined the protein expression profiles of early and epidermal growth factor receptor (EGFR) mutation‐positive lung adenocarcinomas. Methods Fifteen cases of small and EGFR mutation‐positive adenocarcinomas were collected, including AIS, MIA, and small invasive adenocarcinoma (SIA). We examined their protein expression profiles by tandem mass tag (TMT)‐labeling liquid chromatography‐mass spectrometry (LC–MS/MS) and compared the results between AIS and MIA versus SIA. The differentially expressed proteins were then verified by Western blot analysis and immunohistochemistry (IHC). The clinicopathological implications of the proteins were also examined by IHC. Results A total of 4220 proteins were identified by LC–MS/MS analysis. Pathway analysis of the differentially expressed proteins revealed that pathways related to interferon α/β signaling, glutamate and glutamine metabolism, and gluconeogenesis were upregulated in SIA relative to AIS. Among the 13 differentially expressed proteins, cellular retinoic acid binding protein 2 (CRABP2), delta(24)‐sterol reductase (DHCR24), and adenylate kinase 4 (AK4) were expressed significantly more strongly in SIA than in AIS. Patients with high expression of CRABP2, DHCR24, and AK4 showed a significantly poorer outcome than those with low expression. Conclusion In comparison with AIS, SIA shows differences in several different protein expression pathways. Furthermore, CRABP2, DHCR24, and AK4 are useful IHC markers for diagnosis of lung adenocarcinoma invasiveness and may be associated with malignant progression of AIS.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    URL: Article
    DOI: 10.1002/cam4.v12.9
    DOI: 10.1002/cam4.5766
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2659751-2
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  • 2
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    Cyclophilin A expression and its prognostic significance in lung adenocarcinoma
    Wiley ; 2017
    In:  Pathology International Vol. 67, No. 11 ( 2017-11), p. 555-563
    Details
    In: Pathology International, Wiley, Vol. 67, No. 11 ( 2017-11), p. 555-563
    Abstract: Cyclophilin A (CypA) has been reported to be upregulated in malignant tumors. CypA expression is thought to be associated with acquisition of tumor growth and anti‐apoptotic function. Although upregulation of CypA has been reported in lung adenocarcinoma, its clinicopathological significance and roles in malignant progression remain unclear. Here we investigated the implications of CypA expression for outcome in patients with lung adenocarcinoma. Lung adenocarcinoma specimens from 198 cases were selected and reclassified according to the World Health Organization classification (4th edition) and the Noguchi classification. CypA expression was assessed by immunohistochemistry, and the H‐score was calculated on the basis of intensity and proportion. The specificity of the antibody used was confirmed by Western blotting and the cut‐off point was determined from the ROC curve. Sixty‐seven cases (33.8%) had low CypA expression (CypA‐L group) and 131 (66.2%) had high CypA expression (CypA‐H group). Many cases of adenocarcinoma in situ were CypA‐L, and advanced adenocarcinomas tended to be classified as CypA‐H. Clinically, patients with CypA‐H tumors showed a significantly poorer prognosis than those with CypA‐L tumors. This is the first investigation of the implications of the CypA expression level in terms of the clinical characteristics of resected lung adenocarcinomas.
    Type of Medium: Online Resource
    ISSN: 1320-5463 , 1440-1827
    URL: Issue
    URL: Article
    DOI: 10.1111/pin.v67.11
    DOI: 10.1111/pin.12593
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2008574-6
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  • 3
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    Online Resource
    Dickkopf‐related protein 3 promotes cell adhesion and invasion during progression of lung adenocarcinoma
    Wiley ; 2019
    In:  Pathology International Vol. 69, No. 11 ( 2019-11), p. 646-654
    Details
    In: Pathology International, Wiley, Vol. 69, No. 11 ( 2019-11), p. 646-654
    Abstract: Dickkopf‐related protein 3 (DKK3) is one of the DKK family (DKK1‐4), an evolutionally conserved group of secreted glycoproteins characterized by two distinct cysteine‐rich domains. DKK3 is considered to be a tumor suppressor gene. However, it has been shown that 30–50% of various cancers are DKK3‐positive, suggesting that DKK3 may have an additional function other than tumor suppression. In this study, we focused on lung adenocarcinoma, which is the major histological type of lung cancer. We analyzed the relationship between DKK3 expression and clinicopathological features by immunohistochemistry, using 200 lung adenocarcinoma specimens. We found that 40.5% and 59.5% of cases were DKK3‐positive and ‐negative, respectively, and that positive cases had a greater tendency for progression than negative cases ( P   〈  0.05). Furthermore, in vitro analyses demonstrated that DKK3 suppression affected cell adhesion in three DKK3‐expressing lung adenocarcinoma cell lines and that DKK3‐knockdown cells were less invasive in comparison to control cells. These results suggest that DKK3 plays a role in the progression of lung adenocarcinoma by promoting cell adhesion and invasion. DKK3 might be a new extracellular cancer therapeutic target, and it seems important to clarify molecular mechanisms underlying the DKK3 functions depending on cell context.
    Type of Medium: Online Resource
    ISSN: 1320-5463 , 1440-1827
    URL: Issue
    URL: Article
    DOI: 10.1111/pin.v69.11
    DOI: 10.1111/pin.12863
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2008574-6
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  • 4
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    Online Resource
    High expression of ovarian cancer immunoreactive antigen domain containing 2 (OCIAD2) is associated with poor prognosis in lung adenocarcinoma
    Wiley ; 2018
    In:  Pathology International Vol. 68, No. 11 ( 2018-11), p. 596-604
    Details
    In: Pathology International, Wiley, Vol. 68, No. 11 ( 2018-11), p. 596-604
    Abstract: The clinicopathological implications of ovarian cancer immunoreactive antigen domain containing 2 (OCIAD2) in lung adenocarcinoma were investigated. The expression of OCIAD2 in 191 surgically resected lung adenocarcinomas was examined using immunohistochemistry. OCIAD2 expression was quantified using the H‐score and dichotomized as high or low. High OCIAD2 protein expression was significantly correlated with vascular invasion ( P  = 0.0018), lymphatic permeation ( P  = 0.049), T factor ( P  = 0.0024), and pathological stage ( P  = 0.0003). High OCIAD2 expression was significantly associated with poorer overall survival (OS) ( n  = 191, P  = 0.0325). In peripheral‐type lung adenocarcinomas ( n  = 161), high OCIAD2 expression was significantly associated with both poorer OS ( P  = 0.0214) and poorer disease‐free survival ( P  = 0.0496). Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) showed weaker OCIAD2 expression than invasive adenocarcinoma. Among small adenocarcinomas measuring 2 cm or less in greatest dimension classified according to the Noguchi's classification ( n  = 79), invasive adenocarcinomas showed significantly higher OCIAD2 expression than non‐invasive adenocarcinomas ( P  = 0.0007). Interestingly, OCIAD2 was expressed heterogeneously even within a tumor, and its expression was higher in areas of invasion than in areas of in situ spread. Our results suggest that OCIAD2 could be a useful prognostic biomarker of lung adenocarcinoma.
    Type of Medium: Online Resource
    ISSN: 1320-5463 , 1440-1827
    URL: Issue
    URL: Article
    DOI: 10.1111/pin.v68.11
    DOI: 10.1111/pin.12724
    Language: English
    Publisher: Wiley
    Publication Date: 2018
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  • 5
    Online Resource
    Online Resource
    Developmental markers of ganglion cells in the enteric nervous system and their application for evaluation of H irschsprung disease
    Wiley ; 2014
    In:  Pathology International Vol. 64, No. 9 ( 2014-09), p. 432-442
    Details
    In: Pathology International, Wiley, Vol. 64, No. 9 ( 2014-09), p. 432-442
    Abstract: H irschsprung disease ( HSCR ) is a congenital disease resulting from failure of neural crest‐derived ganglion cells to colonize the colon. Conventional diagnostic methods are insufficient for evaluating the ‘functional’ prognosis of HSCR . In order to elucidate the maturation of ganglion cells, 17 immunohistochemical markers were examined. We examined the digestive tracts of 2 human early delivery patients, 2 miniature swine fetuses, 4 little infants, 3 infants, 3 children, 6 adults, and 3 aged individuals. With increasing age, the labeling index ( LI ) for both calretinin and tyrosine hydroxylase ( TH ) increased, whereas that for SOX 10 decreased. We then examined the ‘transitional zone’ of HSCR in 21 affected patients and 18 controls for these three markers. The LI of calretinin and TH were significantly lower than in the controls (median: 3.7 in HSCR and 8.2 in controls, P 〈 0.001, median: 27.9 in HSCR and 44.4 in controls, P 〈 0.001, respectively). In contrast, the LI for SOX 10 showed no significant difference (median: 33.7 in HSCR and 29.2 in controls, P = 0.666) however, hierarchical cluster analysis was able to divide HSCR patients into two groups. These results suggest that immature ganglion cells are present in the transitional zone of HSCR , and that HSCR may have two different pathophysiological processes.
    Type of Medium: Online Resource
    ISSN: 1320-5463 , 1440-1827
    URL: Issue
    URL: Article
    DOI: 10.1111/pin.2014.64.issue-9
    DOI: 10.1111/pin.12191
    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 2008574-6
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  • 6
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    Lung carcinoma representing initially with subacute bilateral isolated hypoglossal nerve palsy: A case of atypical occipital condyle syndrome
    Wiley ; 2019
    In:  Neurology and Clinical Neuroscience Vol. 7, No. 1 ( 2019-01), p. 37-39
    Details
    In: Neurology and Clinical Neuroscience, Wiley, Vol. 7, No. 1 ( 2019-01), p. 37-39
    Abstract: We herein report the case of a 73‐year‐old man presenting bilateral hypoglossal nerve palsy as the initial symptom of metastatic lung cancer. The patient had subacute dysarthria and dysphagia caused by a disturbance in the protrusion of his tongue; He also had severe constant occipital pain, which prevented sleep. MRI showed a mass with contrast enhancement at the skull base. Squamous cell carcinoma was shown by bronchoscopic lung biopsy. In cases of hypoglossal nerve palsy with preceding severe ipsilateral occipital pain, metastatic cancer to the skull base should be considered as occipital condyle syndrome, even though the hypoglossal nerve palsy is bilateral or the patient has no history of malignant tumors. Occipital condyle syndrome with bilateral hypoglossal paralysis may be important as a sign of poor prognosis in cancer.
    Type of Medium: Online Resource
    ISSN: 2049-4173 , 2049-4173
    URL: Issue
    URL: Article
    DOI: 10.1111/ncn3.2019.7.issue-1
    DOI: 10.1111/ncn3.12240
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2706717-8
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  • 7
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    The prognostic significance of N‐myc downregulated gene 1 in lung adenocarcinoma
    Wiley ; 2018
    In:  Pathology International Vol. 68, No. 4 ( 2018-04), p. 224-231
    Details
    In: Pathology International, Wiley, Vol. 68, No. 4 ( 2018-04), p. 224-231
    Abstract: It has been reported that N‐myc downstream regulated gene 1 (NDRG1) is related to the prognosis of non‐small cell lung cancer (NSCLC), and associated with c‐Myc degradation in NSCLC cell lines. However, the relationship of NDRG1 to prognosis or c‐Myc expression in lung adenocarcinoma has not been well clarified. The present study was designed to investigate the prognostic significance of NDRG1 and/or c‐Myc expression in lung adenocarcinoma using immunohistochemistry with a tissue microarray. We examined 184 lung adenocarcinomas and observed low expression of NDRG1 in adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), whereas high expression of NDRG1 was seen in invasive adenocarcinoma. Each of the clinicopathological features except age was significantly correlated with NDRG1 expression. Kaplan‐Meier curves indicated that high expression of NDRG1 was significantly correlated with poor prognosis in comparison with low expression (log‐rank, P   〈  0.001). Univariate and multivariate analyses indicated that vascular invasion ( P  = 0.012), lymphatic permeation ( P  = 0.038), and NDRG1 expression ( P  = 0.026) were independent prognostic factors. Expression of NDRG1 and positivity for c‐Myc were significantly correlated ( P  = 0.005). These findings indicate that NDRG1 expression is associated with both prognosis and c‐Myc expression in lung adenocarcinoma.
    Type of Medium: Online Resource
    ISSN: 1320-5463 , 1440-1827
    URL: Issue
    URL: Article
    DOI: 10.1111/pin.v68.4
    DOI: 10.1111/pin.12644
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2008574-6
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