JaLCDOI 10.18926/AMO/52785
FullText URL 68_4_191.pdf
Author Shien, Kazuhiko| Yamamoto, Hiromasa| Soh, Junichi| Miyoshi, Shinichiro| Toyooka, Shinichi|
Abstract Non-small cell lung cancer (NSCLC) harboring an activating mutation within the epidermal growth factor receptor (EGFR) was defined as a clinically distinct molecular group. These lesions show oncogene addiction to EGFR and dramatic responses to the EGFR tyrosine kinase inhibitors (TKIs). Several large Phase III trials have shown that EGFR-TKIs improved the progression-free survival of patients with EGFR mutant NSCLC compared to conventional chemotherapy. However, the long-term effectiveness of EGFR-TKIs is usually limited because of acquired drug resistance. To overcome this resistance to EGFR-TKIs, it will be essential to identify the specific mechanisms underlying the resistance. Many investigators have attempted to identify the mechanisms using preclinical models and drug-resistant clinical samples. As a result, several mechanisms have been showed to be responsible for the resistance, but not all of the relevant mechanisms have been uncovered. In this review, we provide an overview of mechanisms underlying drug-resistance to EGFR-TKIs, focusing on results obtained with preclinical models, and we present some possible strategies to overcome the EGFR-TKI resistance.
Keywords non-small cell lung cancer EGFR mutation tyrosine-kinase inhibitor drug resistance cancer stem cell
Amo Type Review
Publication Title Acta Medica Okayama
Published Date 2014-08
Volume volume68
Issue issue4
Publisher Okayama University Medical School
Start Page 191
End Page 200
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2014 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 25145405
Web of Science KeyUT 000340687500001
JaLCDOI 10.18926/AMO/54978
FullText URL 71_2_105.pdf
Author Shinya, Takayoshi| Tanaka, Takashi| Soh, Junichi| Matsushita, Toshi| Sato, Shuhei| Toyooka, Shinichi| Yoshino, Tadashi| Miyoshi, Shinichiro| Kanazawa, Susumu|
Abstract We retrospectively assessed the dual-time-point (DTP) F-18 FDG PET/CT findings of thymic epithelial neoplasms (TENs) and investigated the diagnostic capacity of PET/CT compared to that of CT for predicting carcinoma. We calculated the ratio of the standardized uptake value of the tumor and that of the aortic arch (T/M ratio) for both the 90-min early scan and the 2-h delayed scan in 56 TEN patients. We used a multivariate logistic regression (MLR) analysis to estimate the CT features of carcinoma. We compared the diagnostic capacities of PET/CT and chest CT using receiver operating characteristic (ROC) analyses. The ROC curve revealed that the appropriate cut-off T/M ratio value for the highest accuracy was 2.39 with 75.0% accuracy. The area under the curve (AUC) was 0.855. The statistical analyses for DTP scans of 35 TEN patients demonstrated 74.3% accuracy and 0.838 AUC for the early scan versus 82.9% and 0.825 for the delayed scan. The MLR analysis indicated that mediastinal fat infiltration was a predictor of carcinoma. The ROC curve obtained for the model yielded an AUC of 0.853. Delayed scanning could improve the diagnostic capacity for carcinoma. The T/M ratio and mediastinal fat infiltration are predictive of carcinoma with moderate diagnostic accuracy.
Keywords thymic epithelial neoplasm thymic carcinoma thymoma dual-time-point PET/CT chest CT
Amo Type Original Article
Publication Title Acta Medica Okayama
Published Date 2017-04
Volume volume71
Issue issue2
Publisher Okayama University Medical School
Start Page 105
End Page 112
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2017 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 28420891
Author Hayashi, Tatsuro| Asano, Hiroaki| Toyooka, Shinichi| Tsukuda, Kazunori| Soh, Junichi| Shien, Tadahiko| Taira, Naruto| Maki, Yuho| Tanaka, Norimitsu| Doihara, Hiroyoshi| Nasu, Yasutomo| Huh, Nam-ho| Miyoshi, Shinichiro|
Published Date 2012-05
Publication Title Journal of Cancer Research and Clinical Oncology
Volume volume138
Issue issue5
Content Type Journal Article
JaLCDOI 10.18926/AMO/53907
FullText URL 69_6_333.pdf
Author Ito, Maiko| Shien, Tadahiko| Kaji, Mitsumasa| Mizoo, Taeko| Iwamoto, Takayuki| Nogami, Tomohiro| Motoki, Takayuki| Taira, Naruto| Doihara, Hiroyoshi| Miyoshi, Shinichiro|
Abstract We evaluated the usefulness of preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) examinations to predict the pathological features in primary breast cancer. In particular, we evaluated the correlation between the maximum standardized uptake values (SUVmax) obtained by 18F-FDG PET/CT and the Ki67 expression in estrogen receptor (ER)-positive invasive ductal carcinoma (IDC). Primary IDC patients operated between March 2009 and July 2013 at Okayama University Hospital were enrolled. We evaluated the correlations between the SUVmax and age, postoperative pT, histological grade, lymph vascular invasion, status of hormone receptor, human epidermal growth factor receptor 2 (HER2), Ki67 expression and node status. The Ki67 expression was classified as high (>14%) versus low (<14%). We enrolled 138 patients with IDC. Their median SUVmax was 3.85 (range:0-52.57). In a univariate analysis, the SUVmax was significantly related to age, pT, histological grade, lymphovascular invasion, hormone receptor status, HER2 status, node status and Ki67. In the 113 patients with ER-positive IDC, there was a significant correlation between Ki67 and SUVmax (p=0.0030). The preoperative 18F-FDG PET/CT results of IDC patients had significant relationships with pathological status parameters. The determination of the preoperative SUVmax might help classify Luminal A and Luminal B patients among luminal-type breast cancer patients.
Keywords breast cancer invasive ductal carcinoma 18F-fluorodeoxyglucose positron emission tomography/computed tomography maximum standardized uptake values clinicopathological features
Amo Type Original Article
Publication Title Acta Medica Okayama
Published Date 2015-12
Volume volume69
Issue issue6
Publisher Okayama University Medical School
Start Page 333
End Page 338
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2015 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 26690243
Web of Science KeyUT 000368434500002
JaLCDOI 10.18926/AMO/54606
FullText URL 70_5_421.pdf
Author Ohki, Takashi| Sugimoto, Seiichiro| Kurosaki, Takeshi| Otani, Shinji| Miyoshi, Kentaroh| Yamane, Masaomi| Miyoshi, Shinichiro| Oto, Takahiro|
Abstract Stent placement is an essential treatment for airway diseases. Although self-expandable metallic stents and silicone stents are commonly applied for the treatment of airway diseases, these stents are unsuitable for the treatment of small airway diseases encountered in pediatric patients and lung transplant recipients with airway complications. Currently, only vascular balloon-expandable metallic stents are available for the treatment of small airway diseases; however, little research has been conducted on the use of these stents in this field. We have launched a prospective feasibility study to clarify the safety and efficacy of balloon-expandable metallic stents for the treatment of airway diseases.
Keywords metallic stent airway disease lung transplantation airway complication airway malignancy
Amo Type Clinical Study Protocols
Publication Title Acta Medica Okayama
Published Date 2016-10
Volume volume70
Issue issue5
Publisher Okayama University Medical School
Start Page 421
End Page 424
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2016 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 27777440
Web of Science KeyUT 000388098700017
JaLCDOI 10.18926/AMO/46629
FullText URL 65_3_179.pdf
Author Teramen, Hirotake| Tsukuda, Kazunori| Tanaka, Norimitsu| Ueno, Tsuyoshi| Kubo, Takafumi| Ando, Midori| Soh, Junichi| Asano, Hiroaki| Pass, Harvery I.| Toyooka, Shinichi| Miyoshi, Shinichiro|
Abstract Suppression of p21 has been implicated in the genesis and progression of many human malignancies. DNA methylation is an important mechanism of gene silencing in human malignancies. In this study, we examined the expression status and aberrant methylaion of p21 in lung cancers and malignant pleural mesotheliomas (MPM). We used 12 small cell lung cancer (SCLC) cell lines, 13 non-small cell lung cancer (NSCLC) cell lines, 50 primary NSCLCs, 6 MPM cell lines and 10 primary MPMs. The expression and methylation of p21 was examined by reverse transcription-PCR (RT-PCR), Western blotting and methylation-specific PCR (MSP) assay. Loss of p21 protein expression was observed in 7 SCLC cell lines (58.3%), 5 NSCLC cell lines (38.5%) and 3 MPM cell lines (50%) while mRNA expression was lost in 2 SCLC cell lines (16.7%), 2 NSCLC cell lines (15.4%) and none of the MPM cell lines. Aberrant methylation of p21 was found in 8.3% of SCLC cell lines, 30.2% of NSCLCs and 6.3% of MPMs. Among primary NSCLCs, methylation in adenocarcinomas was significantly more frequent than in squamous cell carcinomas. Loss of p21 expression was frequently observed in lung cancers and MPMs and aberrant methylation was one of the mechanisms of suppression of p21, especially in NSCLCs.
Keywords p21 methylation lung cancer mesothelioma
Amo Type Original Article
Publication Title Acta Medica Okayama
Published Date 2011-06
Volume volume65
Issue issue3
Publisher Okayama University Medical School
Start Page 179
End Page 184
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language English
Copyright Holders CopyrightⒸ 2011 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 21709715
Web of Science KeyUT 000292017500004