記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Platinum-based combination therapy plus a programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitor is a standard treatment for patients with stage IV non-small cell lung cancer. However, necitumumab is used with gemcitabine and cisplatin as a first-line treatment option for squamous cell lung cancer (SqCLC). Furthermore, the combination of necitumumab with immune checkpoint inhibitors has the potential to enhance tumor immunity and improve the therapeutic effect. Thus, we planned and initiated this phase I/II study to evaluate the safety and efficacy of necitumumab plus pembrolizumab, nanoparticle albumin-bound (nab)-paclitaxel), and carboplatin therapy for patients with previously untreated SqCLC. PATIENTS AND METHODS: In phase I, the primary endpoint is the tolerability and recommended dose of necitumumab combined with pembrolizumab plus nab-paclitaxel and carboplatin. In phase II, the primary endpoint is the overall response rate. Secondary endpoints are disease control rate, progression-free survival, overall survival, and safety. Forty-two patients will be enrolled in phase II. CONCLUSION: This is the first study to investigate the efficacy and safety of necitumumab plus pembrolizumab combined with platinum-based chemotherapy in patients with previously untreated SqCLC.

DOI： 10.1016/j.cllc.2023.01.008

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記述言語：日本語   出版者・発行元：日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会  

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記述言語：英語  

We present a case of a drug-induced sarcoidosis-like reaction (DISR) in a 34-year-old female patient who had been receiving dupilumab for eosinophilic rhinosinusitis, for seven months. Computerized tomography scans revealed multiple lymphadenopathies, and biopsies performed on the lung and skin lesions showed the presence of non-caseating granulomas. The patient's serum levels of soluble interleukin-2 receptor and angiotensin-converting enzyme were elevated. There were no findings of Mycobacterium spp, or any other bacterial infections. Based on these findings, it was suspected that the sarcoidosis-like reaction observed in this patient was caused by dupilumab. Switching the patient's treatment from dupilumab to mepolizumab improved the DISR.

DOI： 10.1016/j.rmcr.2023.101883

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器内視鏡学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: This subanalysis aimed to provide real-world data on venous thromboembolism (VTE) from patients with lung cancer in the Cancer-VTE Registry. METHODS: The primary outcome was the number of baseline VTE events in patients with lung cancer. The 1-year cumulative incidences of symptomatic VTE; composite VTE (symptomatic and incidental VTE requiring treatment); bleeding; cerebral infarction, transient ischemic attack, and systemic embolic events; and all-cause death were calculated. Clinical trial registration: UMIN000024942. RESULTS: The study enrolled a total of 2377 patients with lung cancer; of these, 119 (5.0%) had VTE (six [0.3%], symptomatic, and 113 [4.8%], asymptomatic) and 14 (0.6%) had pulmonary embolism at baseline. During the follow-up period (mean, 337.7 d), the incidence was 0.6% for symptomatic VTE, 1.8% for composite VTE, 1.5% for bleeding events, 1.3% for cerebral infarction, transient ischemic attack, and systemic embolism, and 19.1% for all-cause death. Composite VTE frequency did not vary by anticancer drug type. Patients with (versus without) VTE at baseline had higher hazard ratios (HRs) for composite VTE (unadjusted HR: 5.29; Gray test p < 0.001) and symptomatic VTE (unadjusted HR: 4.89; Gray test p = 0.007). Patients with VTE at baseline had higher HRs for bleeding events (unadjusted HR: 3.27; Gray test p = 0.010) and all-cause death (unadjusted HR: 2.73; log-rank test p < 0.001) than patients without. In multivariable analysis, patients with baseline VTE prevalence and Eastern Cooperative Oncology Group Performance Status of 2 had increased composite VTE risk during cancer therapy. There were no other risk factors for composite VTE. CONCLUSIONS: Our findings emphasize the importance of VTE screening at cancer diagnosis.

DOI： 10.1016/j.jtocrr.2022.100392

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/cas.15228

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim of the present study was to investigate epidermal growth factor receptor (EGFR) mutations as a prognostic factor for postoperative patients with positive EGFR mutations treated with postoperative platinum-based adjuvant chemotherapy (PBAC), and whether two common EGFR mutations exhibit different responses to PBAC. A total of 110 patients who underwent complete surgical resection were enrolled, and overall survival (OS) and disease-free survival (DFS) were investigated based on EGFR mutation status and PBAC. The 3 year OS rate in patient groups were as follows: Patients with EGFR mutations (MT) undergoing PBAC, 89.3%; MT patients without PBAC, 83.3%; wild-type (WT) patients with PBAC, 82.3%; and WT patients without PBAC, 62.2%. Statistically significant differences were observed between WT patients based on PBAC (P=0.026). No statistically significant differences were observed between MT patients with PBAC and MT patients without PBAC. On the basis of mutation subtypes, the 3 year OS rate of patient groups were as follows: Patients with in-frame deletions in exon19 (19 del) with PBAC, 92.3%; patients with 19 del without PBAC, 85.7%; patients with the point mutation L858R inexon21 (21L858R) with PBAC, 86.7%; and patients with 21L858R without PBAC, 81.5%; the respective 3-year DFS rates were 53.8, 14.3, 40.2 and 26.9%. Statistically significant differences were observed in the DFS rates in 19 del patients, which was dependent on PBAC (P=0.040). EGFR mutation-positive patients exhibited a decreased benefit from PBAC for increasing in survival rate compared with WT patients. It may be necessary to consider postoperative strategies based on EGFR mutations and their subtype in the future.

DOI： 10.3892/ol.2019.11050

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.lungcan.2018.08.027

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier Ireland Ltd  

Objectives: The aim of this study was to conduct comparative analyses of the biological malignant potential of clinical stage IA adenocarcinoma using positron emission tomography/computed tomography (PET/CT), high-resolution CT (HRCT), and three-dimensional CT (3DCT). The predictive performance of these parameters was evaluated in terms of clinical outcomes and pathological invasiveness (positive lymphatic permeation, blood-vessel invasion, pleural invasion, and lymph-node metastasis). Materials and methods: We enrolled 170 patients with c-IA adenocarcinoma who underwent PET/CT, HRCT, and 3D reconstruction of lung structures using the Synapse Vincent system (Fujifilm Corporation, Tokyo, Japan) followed by complete resection. Maximum standardized uptake values (SUVmax) of F18-fluorodeoxyglucose and the size and volume of the solid part of the tumor were quantified and analyzed in relation to surgical outcomes. Results: Univariate analysis demonstrated that all the three parameters and whole-tumor volume were associated with unfavorable disease-free survival (DFS), while the volume of the solid part was the independent predictor on multivariate analysis (p &lt
.001). The receiver operating characteristic curves for pathological invasiveness, determined using the variables dichotomized at each cut-off level (SUVmax 2.4
solid-part size 1.23 cm
solid-part volume 779 mm3), showed that all were significantly correlated with pathological invasiveness and prognosis, whereas the combination of SUVmax and the solid-part volume was the most powerful predictor of survival and pathological invasiveness compared to any other parameters: the 4-year DFS and proportion of pathological invasiveness in patients with SUVmax &gt
2.4 and solid-part volume &gt
779 mm3 versus those with SUVmax ≤ 2.4 or solid-part volume ≤779 mm3 were 81.2% versus 98.3% (p &lt
.001) and 84.3% versus 15.1% (p &lt
.001), respectively. Conclusion: In c-IA adenocarcinoma, the volume of the solid part of the tumor was the independent predictor for unfavorable DFS, and the integration of the volume of the solid part and SUVmax was highly beneficial for the prediction of survival and pathological invasiveness.

DOI： 10.1016/j.lungcan.2018.05.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Granulocyte colony stimulating factor (G-CSF)-producing lung cancer occasionally induces severe inflammation with an abnormally high white blood cell count. Herein, we report a 49-year-old man who suffered from resectable G-CSF-producing non-small cell lung cancer with continuous fever and severe anemia. Red blood cell transfusion was necessary for the anemia of inflammation. The patient underwent complete surgical tumor resection. The histopathological diagnosis was a pleomorphic carcinoma at pathological stage IIB. This is apparently the first successful case of surgical resection of G-CSF-producing lung cancer in a patient with severe anemia and uncontrollable fever.

DOI： 10.1007/s11748-018-0914-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Institute of Anticancer Research  

Background/Aim: The transition rate from first-line epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) to cytotoxic chemotherapy (Ct) is poor. The prognosis according to treatment sequence and the reasons patients could not shift from first-line EGFR-TKIs to Ct were herein analyzed. Patients and Methods: Overall, 159 epidermal growth factor receptor mutation-positive adenocarcinoma patients were enrolled in this study. Results: The median survival times of EGFR-TKIs combined with Ct and EGFR-TKIs were 59.8 months and 22.5 months, respectively (p&lt
0.001) and of patients who received EGFR-TKIs first and Ct first were 38.8 months and 66.4 months, respectively (p=0.016). The main reasons patients could not make the transition to Ct was worsening of performance status and patient’s preference. Conclusion: EGFR-TKIs and Ct lead to a good prognosis in EGFR mutation-positive adenocarcinoma patients. It is necessary to consider the timing when changing the treatment strategy before treatment options are limited.

DOI： 10.21873/anticanres.12574

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Small pulmonary nodules have been detected frequently by computed tomography (CT). Lung cancers with cavity formation are also easily detected. There are a few reports focused on the cavity wall, although cancer cells exist along the cavity wall, not inside. We evaluated the impact of cavity wall thickness on prognosis and assessed the clinicopathological features in non-small cell lung cancer (NSCLC) with cavity formation. Methods: Between 2005 and 2011, 1,313 patients underwent complete resection for NSCLC. Of these cases, we reviewed 65 patients (5.0%) diagnosed with NSCLC with cavity formation by chest CT. We classified the patients into three groups based on the maximum cavity wall thickness, namely, ≤4 mm (Group 1, 8 patients), >4 and ≤15 mm (Group 2, 33 patients), and >15 mm (Group 3, 24 patients). Results: The number of patients with pathological whole tumor size >3 cm was 2 (25%) in Group 1, 17 (52%) in Group 2, and 23 (96%) in Group 3 (P<0.001). Cases with lymph node metastasis were 0 (0%) in Group 1, 5 (15%) in Group 2, and 10 (42%) in Group 3 (P=0.016). The 5-year overall survival (OS) rates were 100% in Group 1, 84.0% in Group 2, and 52.0% in Group 3, with significant differences between Group 1 and Group 3 (P=0.044) and between Group 2 and Group 3 (P=0.034). In univariate analysis, neither whole tumor size nor lymph node metastasis was a prognostic factor for OS (P=0.51, P=0.27). Only cavity wall thickness was a significant prognostic factor by multivariate analysis (P=0.009). Conclusions: Maximum cavity wall thickness was an important prognostic factor in NSCLCs with cavity formation, comparable with other established prognostic factors.

DOI： 10.21037/jtd.2018.01.61

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AME Publishing Company  

Background: In patients with bronchial tumors, we frequently consider endoscopic treatment as the first treatment of choice. All computed tomography (CT) must satisfy several conditions necessary to analyze images by Synapse Vincent. To select safer and more precise approaches for patients with bronchial tumors, we determined the indications and efficacy of virtual navigation intervention for the treatment of bronchial tumors. Methods: We examined the efficacy of virtual navigation bronchial intervention for the treatment of bronchial tumors located at a variety of sites in the tracheobronchial tree using a high-speed 3-dimensional (3D) image analysis system, Synapse Vincent. Constructed images can be utilized to decide on the simulation and interventional strategy as well as for navigation during interventional manipulation in two cases. Results: Synapse Vincent was used to determine the optimal planning of virtual navigation bronchial intervention. Moreover, this system can detect tumor location and alsodepict surrounding tissues, quickly, accurately, and safely. The feasibility and safety of Synapse Vincent in performing useful preoperative simulation and navigation of surgical procedures can lead to safer, more precise, and less invasion for the patient, and makes it easy to construct an image, depending on the purpose, in 5-10 minutes using Synapse Vincent. Moreover, if the lesion is in the parenchyma or sub-bronchial lumen, it helps to perform simulation with virtual skeletal subtraction to estimate potential lesion movement. By using virtual navigation system for simulation, bronchial intervention was performed with no complications safely and precisely. Conclusions: Preoperative simulation using virtual navigation bronchial intervention reduces the surgeon's stress levels, particularly when highly skilled techniques are needed to operate on lesions. This task, including both preoperative simulation and intraoperative navigation, leads to greater safety and precision. These technological instruments are helpful for bronchial intervention procedures, and are also excellent devices for educational training.

DOI： 10.21037/jtd.2017.12.35

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

To date, a number of potential biomarkers for lung squamous cell cancer (SCC) have been identified; however, sensitive biomarkers are currently lacking to detect early stage SCC due to low sensitivity and specificity. In the present study, we compared the 7 serum proteomic profiles of 11 SCC patients, 7 chronic obstructive pulmonary disease (COPD) patients and 7 healthy smokers as controls to identify potential serum biomarkers associated with SCC and COPD. Two-dimensional difference gel electrophoresis (2D-DIGE) and mass-spectrometric analysis (MS) using an affinity column revealed two candidate proteins, haptoglobin (HP) and apolipoprotein 4, as biomarkers of SCC, and alpha-1-antichymotrypsin as a marker of COPD. The iTRAQ technique was also used to identify SCC-specific peptides. HP protein expression was significantly higher in SCC patients than in COPD patients. Furthermore, two HP protein peptides showed significantly higher serum levels in SCC patients than in COPD patients. We established novel polyclonal antibodies for the two HP peptides and subsequently a sandwich enzyme-linked immunosorbent assay (ELISA) for the quantification of these specific peptides in patient and control sera. The sensitivity of detection by ELISA of one HP peptide (HP216) was 70% of SCC patients, 40% of COPDs patients and 13% of healthy controls. We also measured CYFRA, a cytokeratin fragment clinically used as an SCC tumor marker, in all the 28 cases and found CYFRA was detected in only seven SCC cases. However, when the measurement of HP216 was combined with that of CYFRA, 100% (10 of 10 patients) of SCC cases were detected. Our proteomic profiling demonstrates that the SCC-specific HP peptide HP216 may potentially be used as a diagnostic biomarker for SCC.

DOI： 10.3892/ijo.2016.3330

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The genus Methylobacterium tolerates hygiene agents like benzalkonium chloride (BAC), and infection with this organism is an important public health issue. Here, we found that the combination of BAC with particular alcohols at nonlethal concentrations in terms of their solitary uses significantly reduced bacterial viability after only 5 min of exposure. Among the alcohols, Raman spectroscopic analyses showed that pentanol (pentyl alcohol [PeA]) and benzyl alcohol (BzA) accelerated the cellular accumulation of BAC. Fluorescence spectroscopic assays and morphological assays with giant vesicles indicated that PeA rarely attacked membrane structures, while BzA increased the membrane fluidity and destabilized the structures. Other fluorescent spectroscopic assays indicated that PeA and BzA inactivate bacterial membrane proteins, including an efflux pump for BAC transportation. These findings suggested that the inactivation of membrane proteins by PeA and BzA led to the cellular accumulation but that only BzA also enhanced BAC penetration by membrane fluidization at nonlethal concentrations.

DOI： 10.1128/AEM.02515-15

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PJD Publications Ltd  

Background: Carcinomatous meningitis (CM) in non-small cell lung cancer (NSCLC) has no standard treatment and poor prognosis, with a median survival of 4-9 weeks. Recently, NSCLC subgroups with driver mutations were identified, with mutation of epidermal growth factor receptor gene (EGFR) being the most frequent. This retrospective study investigated the frequency and characteristics of CM in EGFR-mutated patients. Methods: From April 2007 to June 2013, consecutive NSCLC patients were screened for EGFR mutations using the PNA-LNA PCR Clamp in one institution. Diagnosis of CM was based on the presence of malignant cells in cerebrospinal fluid and/or MRI detection of leptomeningeal enhancement. Incidence and clinical features of CM patients were investigated from medical records. Results: Of 1343 NSCLC patients, 387 (28.8%) harboring EGFR mutations. Thirty-five patients (2.6%) developed CM
the rate of CM in EGFR-mutated patients (25/387, 6.46%) was significantly higher than in patients lacking the mutations (10/956, 1.04%
p &lt
0.01). Multiplex logistic analysis indicated strong associations between CM and EGFR mutation (p &lt
0.0001), brain metastasis (p &lt
0.0001) and non-squamous cell carcinoma histology (p = 0.026). Conclusions: NSCLC patients with EGFR mutations are more likely to develop CM than those with wild EGFR.

DOI： 10.4993/acrt.23.14

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

Afatinib is an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKl). In a randomized phase 1 study (Lux-Lung 3 study) employing patients harboring EGFR mutations, patients administered afatinib show a significantly longer progression free survival time (PFS) than those administered combination chemotherapy comprising cisplatin and pemetrexed. However, most of the patients (95.2%) treated with afatinib experienced diarrhea. In the present report, 16 patients with EGFR mutations were treated by afatinib at our institution from May 2014 to December 2014. Twelve patients were administered a diarrhea prevention herbal medicine, Hange-shashin-to. Seven of 12 patients (58%) had no diarrhea during the 28 days of therapy. All 4 of the patients who did not receive Hange-shashin- to experienced diarrhea above Grade 1 within 6 days of starting therapy. The rate of diarrhea differed significantly between the patients receiving and not receiving Hangeshashin-to. In conclusion, preventive administration of Hange-shashin- to may reduce the occurrence of diarrhea during afatinib treatment.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1158/1535-7163.MCT-13-0448

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記述言語：英語   出版者・発行元：WILEY-BLACKWELL  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: A phase II study was conducted in order to determine the tumor efficacy and tolerance of alternating chemotherapy for extensive-stage small cell lung cancer (ED-SCLC). PATIENTS AND METHODS: Twenty patients with previously-untreated ED-SCLC were enrolled in the study. At least four courses of chemotherapy consisting of alternation of two drug combinations were given: alternating cycles of amrubicin and cisplatin with weekly administration of irinotecan and cisplatin at 3- or 4-week intervals. RESULTS: The overall response rate was 85.0% (17/20). The median duration of overall survival and progression-free survival were 359 days and 227 days, respectively. Hematological toxicity was the main adverse event. Grade 3 or 4 neutropenia, thrombocytopenia and anemia were observed in 20 (100%), 4 (20%) and 6 (30%) patients, respectively. With regard to non-hematological adverse events, grade 3 or 4 anorexia, diarrhea, febrile neutropenia and infection were observed in 5 (25%), 2 (10%), 2 (10%) and 2 (10%) patients, respectively. No treatment-related death occurred during either regimen. CONCLUSION: The novel alternating non-cross-resistant chemotherapy was probably active against ED-SCLC and had acceptable toxicities. Further evaluation of this treatment for ED-SCLC in randomized phase III trials is warranted.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT INST ANTICANCER RESEARCH  

Background: A phase II study was conducted to determine the tumor efficacy and tolerance of alternating chemotherapy in extensive-stage small-cell lung cancer (ED-SCLC). Patients and Methods: Thirty-six patients with previously untreated ED-SCLC were enrolled in the study. At least four courses of chemotherapy consisting of alternation of two drug combinations were given: alternating cycles of etoposide and carboplatin (EC) with weekly administration of irinotecan and cisplatin (IP) at 3- or 4-week intervals. Results: The overall response rate was 81.8%. The median duration of survival and progression-free survival were 314 days and 144 days, respectively. Hematological toxicity was the main adverse event. Grade 3 or 4 neutropenia, thrombocytopenia and anemia were observed in 69.2, 25.6 and 23.1% of the patients, respectively. Severe diarrhea (10.8%) was remarkable during the IP regimen. Conclusion: This novel alternating chemotherapy for patients with ED-SCLC showed moderate tumor efficacy and an acceptable safety profile.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

Although there are three kinds of stupor in psychiatry, dissociative stupor is the most commonly recognized. In psychiatric clinics or emergency rooms, dissociative stupor is common, but in an oncology setting it is hardly known. Therefore, distinguishing dissociative stupor from consciousness disorder is occasionally difficult, especially in the advanced or terminal phase. We report an advanced lung cancer patient who presented dissociative stupor mimicking consciousness disorder. It is necessary to distinguish between consciousness disorder and dissociative stupor. In addition, consultation with a psychiatrist should be taken into consideration.

DOI： 10.1093/jjco/hys053

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Carcinomatous meningitis (CM) is a severe complication of lung cancer. Here, we report on two EGFR-mutated patients who attained relatively long survivals by erlotinib treatment after diagnosis of CM. The first case is a 59-year-old woman who was diagnosed as adenocarcinoma harboring an EGFR mutation (L858R)
her disease was at stage IV with multiple brain metastases. The time from the initial diagnosis of lung cancer to CM was 364 days. Erlotinib was administered for 5 months, and the survival time from the diagnosis of CM was 278 days. The second case is a 60-year-old man who underwent right lower lobe lobectomy and was diagnosed as adenocarcinoma with an EGFR mutation (E746-750 deletion) and at the pathological stage IIA (pT1N2M0). Later, the disease was recurring as brain metastasis, and progressed to CM 637 days after diagnosis of lung cancer. Erlotinib was administered for 5.5 months, and the survival time from the diagnosis of CM was 281 days. These cases indicate that erlotinib is a reasonable option for the treatment of CM in EGFR-mutated patients.

DOI： 10.4993/acrt.20.58

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Background: Idiopathic interstitial pneumonias (IIPs) are among the most common complications in patients with lung cancer. In such patients with cancer, the most serious expression of toxicity in Japan is acute exacerbation of IIPs caused by anticancer treatment. Nevertheless, there has been no consensus and no evidence presented, regarding optimal treatment for advanced lung cancer with IIP.
Patients and Methods: Chemotherapy-naive patients with advanced small cell lung cancer (SCLC) with IIP who were ineligible for curative radiotherapy were enrolled. Patients received carboplatin every 21 days at a dose of area under the curve 6.0 on day 1 and etoposide at a dose of 100 mg/m(2) on days 1 to 3.
Results: Between July 2002 and October 2008, 17 patients with SCLC with IIP, including 14 men, eight of whom were diagnosed with idiopathic pulmonary fibrosis, were enrolled and treated for a mean of 3.5 cycles of carboplatin plus etoposide. One patient (5.9%; 95% confidence interval, 0-18.4%) with clinically confirmed idiopathic pulmonary fibrosis had acute exacerbation of IIPs associated with the treatment. The overall response rate was 88.2%. The median progression-free survival, median survival time, and 1-year survival rate were 5.5 months, 8.7 months, and 29.4%, respectively.
Conclusion: This is the first report indicating that patients with advanced SCLC with IIPs may benefit from chemotherapy. Patients with advanced SCLC with IIP treated with etoposide and carboplatin combination chemotherapy gain benefits, with safety equivalent to that seen in patients without IIP. The results from this study would support, on ethical grounds, the conduct of a large-scale study to evaluate this regimen.

DOI： 10.1097/JTO.0b013e3182103d3c

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

Epithelial to mesenchymal transition (EMT) is induced by transforming growth factor-beta 1 (TGF-beta 1) and is a crucial event for cancer cells to acquire invasive and metastatic phenotypes. However, the signals that induce EMT in cancer cells have yet to be adequately defined. In this study, a proteomic investigation was performed to understand the signaling pathway of the EMT of lung cancer using two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry. The protein expression profiles of A549 were compared to those of A549 cells treated with TGF-beta 1. Of more than 2,000 protein spots shown by 2D-DIGE, 53 were found to be up- or down-regulated upon induction with TGF-beta 1. In the 53 protein. spots, the protein level of heat shock protein (HSP) 27 was found to increase significantly. HSP27 protein was higher in two different lung cancer cell lines, demonstrating the EMT phenomenon with TGF-beta 1. Notably, the silencing of HSP27 enhanced. spindle integration, resulting in an additive effect with TGF-beta 1-induced EMT. Furthermore, the TGF-beta 1-induced HSP27 increase was not affected by the suppression of Smad2 and Smad3 in A549 cells. These results suggest that HSP27 was involved in TGF-beta 1-induced EMT in a Smad-independent manner in lung cancer cells and may provide an effective clinical strategy in lung cancer patients whose tumors are dependent on TGF-beta 1-induced EMT.

DOI： 10.3892/ol.2010.190

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

It is desirable to find more appropriate therapeutic opportunities in non-small-cell lung cancer (NSCLC) due to the current poor prognosis of affected patients. Recently, several histone deacetylase (HDAC) inhibitors, including suberoylanilide hydroxamic acid (SAHA), have been reported to exhibit antitumor activities against NSCLC. S-1, a novel oral fluorouracil anticancer drug, has been developed for clinical use in the treatment of NSCLC in Japan. Using an MTT assay, we analyzed the growth-inhibitory effect of 5-fluorouracil (5-FU), S-1, and SAHA against three NSCLC cell lines, as well as the breast cancer cell line MCF7 which is known to be highly sensitive to 5-FU. Combined treatment with low-dose SAHA enhanced 5-FU- and S-1-mediated cytotoxicity and resulted in synergistic effects, especially in 5-FU-resistant cells. Both the mRNA and protein expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT), which are associated with 5-FU sensitivity/response, were analyzed in the cells undergoing treatment. 5-Fluorouracil-resistant lung cancer cells displayed high expression of TS mRNA and protein. Suberoylanilide hydroxamic acid down-regulated TS mRNA and protein expression, as well as repressed the rapid induction of this factor during 5-FU treatment, in all examined cell types. We also examined the status of the Rb-E2F1 pathway, with SAHA up-regulating p21waf1/cip1 expression via promoter histone acetylation; this, in turn, blocked the Rb-E2F1 pathway. We conclude that combination therapy with SAHA and S-1 in lung cancer may be promising due to its potential to overcome S-1 resistance via modulation of 5-FU/S-1 sensitivity-associated biomarker (TS) by HDAC inhibitor. (Cancer Sci 2010).

DOI： 10.1111/j.1349-7006.2010.01559.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

Previously, we performed a molecular pharmacological study that applied a combination of DNA microarray-based gene expression profiling and drug sensitivity tests in vitro with a view to designing an improved chemotherapeutic strategy for advanced lung cancer Utilizing recent key technological advances in proteomics, particularly antibody array-based methodologies, the current study aimed to examine the benefit of protein expression profiling in an analogous molecular pharmacological context We performed protein expression analysis in a panel of lung cancer cell lines via an antibody array approach Using a modified NCI program, we related cell line-specific proteomic profiles to the previously determined cytotoxic activity of a selection of commonly used anticancer agents, namely docetaxel, paclitaxel, gemcitabine, vinorelbine, 5-fluorouracil (5-FU), SN38, cisplatin (CDDP) and carboplatin (CBDCA) In addition, we compared these results with those obtained from our prior DNA microarray-based transcriptomic study In our expression-drug correlation analysis using antibody array, gemcitabine consistently belonged to an isolated cluster Docetaxel, paclitaxel, 5-FU, SN38, CBDCA and CDDP were gathered together into one large cluster These results coincided with those generated by the prior transcriptomic study Various genes were commonly listed that differentiated gemcitabine from the others The identified factors associated with drug sensitivities were different between both analyses Our proteomic profiling data provided confirmation of the previous transcript expression-drug sensitivity correlation analysis These results suggest that chemotherapy regimens that include gemcitabine should be evaluated in second-line chemotherapy in cases where the first-line chemotherapy did not include this drug Protein expression-drug sensitivity correlations in lung cancer cells in vitro may provide useful information in determining the most appropriate therapeutic options for lung cancer patients

DOI： 10.3892/etm_00000007

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL TRIBUNE INC  

We herein describe a patient we encountered in whom mediastinal lymph node metastasis of lung cancer with an unknown primary lesion was complicated by both an endocrine abnormality and acanthosis nigricans. A 66-year-old male visited a local hospital and was diagnosed as having acanthosis nigricans. The patient was referred to our hospital for further examination. Computed tomography scans of the chest and the abdomen showed no adverse findings except for an enlargement of the mediastinal lymph node. No malignant lesions were detected in examinations of the upper gastrointestinal tract. Based on the above findings, the lesion was thus considered to possibly be mediastinal lymph node metastasis of an unknown primary tumor or malignant lymphoma. A thoracoscopic biopsy of the mediastinal lymph node was performed. The patient was diagnosed to have mediastinal lymph node metastasis of lung cancer with an unknown primary lesion and endocrine abnormality resulting from paraneoplastic syndrome. Palliative radiation therapy was initiated to prevent superior vena cava syndrome and esophageal passage failure or dysphagia. The cutaneous lesions markedly improved thereafter. The serum levels of adrenocorticotropic hormone decreased. (Ann Thorac Cardiovasc Surg 2009; 15: 397-400)

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATL ACAD SCIENCES  

Fifteen percent of lung cancer cases occur in never-smokers and show characteristics that are molecularly and clinically distinct from those in smokers. Epidermal growth factor receptor (EGFR) gene mutations, which are correlated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), are more frequent in never-smoker lung cancers. In this study, microRNA (miRNA) expression profiling of 28 cases of never-smoker lung cancer identified aberrantly expressed miRNAs, which were much fewer than in lung cancers of smokers and included miRNAs previously identified (e. g., up-regulated miR-21) and unidentified (e. g., down-regulated miR-138) in those smoker cases. The changes in expression of some of these miRNAs, including miR-21, were more remarkable in cases with EGFR mutations than in those without these mutations. A significant correlation between phosphorylated-EGFR (p-EGFR) and miR-21 levels in lung carcinoma cell lines and the suppression of miR-21 by an EGFR-TKI, AG1478, suggest that the EGFR signaling is a pathway positively regulating miR-21 expression. In the never-smoker-derived lung adenocarcinoma cell line H3255 with mutant EGFR and high levels of p-EGFR and miR-21, antisense inhibition of miR-21 enhanced AG1478-induced apoptosis. In a never-smoker-derived adenocarcinoma cell line H441 with wildtype EGFR, the antisense miR-21 not only showed the additive effect with AG1478 but also induced apoptosis by itself. These results suggest that aberrantly increased expression of miR-21, which is enhanced further by the activated EGFR signaling pathway, plays a significant role in lung carcinogenesis in never-smokers, as well as in smokers, and is a potential therapeutic target in both EGFR-mutant and wild-type cases.

DOI： 10.1073/pnas.0905234106

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

DOI： 10.1272/jnms.76.44

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

Patients with idiopathic pulmonary fibrosis (IPF) have an increased risk of developing lung cancer. To identify key molecules involved in malignant transformation in IPF, we analyzed the expression profiles of lung and lung tumor tissue from patients with lung cancer and IPF (lung cancer/IPF) using cDNA arrays and real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Reduced expression of the Smad4 gene was identified in all eight tumor samples from the lung cancer/IPF patients using real-time RT-PCR, Expression levels of Smad4 were significantly lower in tumors from lung cancer/IPF patients than in those from lung cancer patients without IPF or in lung cancer cell lines (p&lt;0.01). Mutational analysis of TGF-beta type II receptor and Smad4 was performed using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). The methylation status of the Smad4 promoter was analyzed using methylation-specific PCR with subsequent sequence analysis. No mutations were detected in the eight tumor samples, but hypermethylated regions were detected in the Smad4 promoter in two of the eight tumors with reduced Smad4 expression. Promoter reporter assays showed that the activity of the Smad4 promoter containing the sequence of the methylated region was significantly stronger than that of the Smad4 promoter with a deleted methylated region (p&lt;0.002). Our findings indicate that the loss of the growth inhibitory response to TGF-beta signaling may be crucial in pulmonary carcinogensis or in the progression of lung cancer in IPF patients in whom TGF-beta is overexpressed; hypermethylation of the Smad4 promoter region may be one mechanism by which this occurs. These findings are useful for the development of preventive measures or treatment for lung cancer patients with IPF.

DOI： 10.3892/mmr_00000064

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Objective and Methods Idiopathic interstitial pneumonias (IIPs) frequently occur in association with lung cancer. However, there is no consensus on the best treatment of acute exacerbation of IIP in lung cancer patients (LC with IIP), including those with iatrogenic acute lung injury resulting from cancer treatments. We aimed to identify an appropriate strategy for treatment of this condition. We analyzed clinical features of 120 LC with IIP, retrospectively.
Results The incidence of acute exacerbation related to anticancer treatment was 22.7%; when the incidence was examined separately for patients receiving chemotherapy or the best supportive care, the incidence was 20.0% and 31.3%, respectively. Additional investigations should be directed to finding suitable regimens for treatment of LC with IIP and the selection of appropriate patients with LC with IIP for chemotherapy. The incidence of acute exacerbation caused by combination regimens of carboplatin + paclitaxel or a platinum agent + etoposide was significantly lower than that of other regimens (0% vs. 18%, respectively; p=0.025, Fisher&apos;s Exact Test). Patients with high levels of C-reactive protein before chemotherapy had a significantly higher risk of developing acute exacerbation (odds ratio 5.60, p=0.028).
Conclusion There was no evidence that anticancer treatment, including chemotherapy, should be avoided in LC with IIP. To establish an appropriate cancer treatment for LC with IIP, a prospective clinical study should be performed to evaluate various treatment modalities in a larger patient population.

DOI： 10.2169/internalmedicine.48.1650

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

To ascertain the potential for histone deacetylase (HDAC) inhibitor-based treatment in non-small cell lung cancer (NSCLC), we analyzed the antitumor effects of trichostatin A (TSA) and suberoylanilide hydroxamic acid (vorinostat) in a panel of 16 NSCLC cell lines via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. TSA and vorinostat both displayed strong antitumor activities in 50% of NSCLC cell lines, suggesting the need for the use of predictive markers to select patients receiving this treatment. There was a strong correlation between the responsiveness to TSA and vorinostat (P &lt; 0.0001). To identify a molecular model of sensitivity to HDAC inhibitor treatment in NSCLC, we conducted a gene expression profiling study using cDNA arrays on the same set of cell lines and related the cytotoxic activity of TSA to corresponding gene expression pattern using a modified National Cancer Institute program. In addition, pathway analysis was done with Pathway Architect software. We used nine genes, which were identified by gene-drug sensitivity correlation and pathway analysis, to build a support vector machine algorithm model by which sensitive cell lines were distinguished from resistant cell lines. The prediction performance of the support vector machine model was validated by an additional nine cell lines, resulting in a prediction value of 100% with respect to determining response to TSA and vorinostat. Our results suggested that (a) HDAC inhibitors may be promising anticancer drugs to NSCLC and (b) the nine-gene classifier is useful in predicting drug sensitivity to HDAC inhibitors and may contribute to achieving individualized therapy for NSCLC patients.

DOI： 10.1158/1535-7163.MCT-07-2140

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

It is known that an epidermal growth factor receptor (EGFR) gene mutation(s) is present in a percentage of non-small cell lung cancers (NSCLCs). Gefitinib, an inhibitor of the tyrosine kinase activity of EGFR, is effective on most of them. The EGFR mutation status alone cannot fully predict the response to gefitinib and the prognosis for the patients. We hypothesized that information on the expression levels of phosphorylated-EGFR and -Akt, and E-cadherin, alone or in combination with information on the EGFR mutation, may refine our ability of prediction. We investigated 24 NSCLCs that had recurred after surgery and were treated with gefitinib. Specimens resected by surgery were subjected to the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp reaction to determine the EGFR mutation status, and to immunohistochemical staining of phosphorylated-EGFR and -Akt, and E-cadherin to determine their expression levels. The EGFR mutation status was predictive of responsive disease (complete response: CR + partial response: PR) and controlled disease (CR + PR + stable disease: SD). Positive E-cadherin staining was predictive of longer time to progression (12.4 vs. 5.9 months, p&lt;0.05) and overall survival (OS) (18.4 vs. 13.0 months, p&lt;0.05). Together the patients with an EGFR mutation and the patients with positive E-cadherin staining defined a patient group with a median OS of 18.4 months and excluded the patient group with the median OS of 3.7 months. Neither p-Akt nor p-EGFR staining was associated with the response and survival. In patients with surgically resected NSCLC tumors, the EGFR mutation status and E-cadherin staining can select patients who will benefit from gefitinib therapy.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1272/jnms.75.53

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

The response rates to combination chemotherapy in metastatic non-small cell lung cancer (NSCLC) cases have been reported to be lower than those to induction chemotherapy in locally advanced cases. To understand the relationship between highly metastatic potential and chemosensitivity, we examined the drug sensitivity of a highly metastatic human lung adenocarcinoma cell subpopulation, PC9/f14, which had been previously established in an experimental metastasis model, to commonly used anti-cancer agents (paclitaxel, SN38, gemcitabine, vindesine, etoposide, cisplatin, and carboplatin) via the 3-(4, 5-dimethylthiazol-2-yl)2, 5-diphenyltetrazolium bromide assay. We found that the PC9/f14 subpopulation, which we previously reported to be resistant to gefitinib, was also resistant to gemcitabine (2'2'-difluoro-2'-deoxy-cytidine), a nucleoside analogue. To clarify the mechanisms of the gemcitabine resistance in this subpopulation, we screened the changes to the protein expression profiles of these cells after exposure to gemcitabine, using a 224-antibody microarray analysis. The exposure to gemcitabine in this subpopulation induced an increase in the expression level of the Bcl-X protein, although this expression remained unchanged in the parent cells. Apoptosis following gemcitabine exposure was depressed in the PC9/f14 subpopulation compared with parent cells, as assessed by flow cytometry and TUNEL assay. In addition, knock-down of Bcl-X by RNA interference methodology induced the recovery of gemcitabine sensitivity in PC9/f14. Phosphorylated Akt, which seems to be involved in the gefitinib resistance of this subpopulation, did not change after gemcitabine exposure. In conclusion, this highly metastatic lung cancer subpopulation had multi-resistant characteristics, to both gemcitabine and gefitinib, which were achieved in different ways, during the process of obtaining its highly metastatic potential. The combination of anti-cancer drugs and inhibition of the molecules related with apoptosis and/or Akt pathway might be beneficial in the treatment of metastatic NSCLC.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

To understand the mechanisms of PTEN inactivation, which is reported to be involved in tumor progression and drug resistance in lung cancer, we analyzed the expression levels of PTEN at mRNA and protein levels, along with the genetic and epigenetic status of the PTEN gene, in a panel of lung cancer cell lines. Western blot analysis showed that six out of 25 (24%) cell lines displayed low expression of PTEN protein. The level of PTEN mRNA correlated well with corresponding protein expression in each of these six cell lines. In two of the six cell lines genomic analysis revealed homozygous deletions of the PTEN gene. Another two of the six cell lines displayed hypermethylation of the PTEN gene promoter assessed by methylation-specific PCR. The levels of PTEN mRNA and protein expression in PC9/f9 and PC9/f14 cells, which are gefitinib-resistant derivatives of the gefitinib-sensitive cell line, PC9, were reduced compared to the parental line. After treatment with the demethylating agent 5-aza-2'deoxycytidine (5-AZA) and the histone deacetyl-transferase (HDAC) inhibitor Trichostatin A (TSA), the expression levels of PTEN mRNA and protein in these four cell lines (PC9/f9, PC9/f14, PC10 and PC14) were actually restored. In summary, reduction in PTEN protein expression was regulated by histone deacetylation and hypermethylation of the gene promoter, as well as homozygous deletion. In addition, we demonstrated that the combination treatment of gefitinib and TSA induced significant growth inhibition in gefitinib-resistant PC9/f9 and PC9/f14 cells. These findings suggest that the combination of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib with the demethylating agent 5-AZA and the HDAC inhibitor TSA may be a useful strategy for the treatment of some lung cancers,

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

We investigated the aberrant expression of plasma proteins in patients with pancreatic cancer. High-abundance plasma proteins (albumin, transferrin, haptoglobin, alpha-1-antitrypsin, IgG and IgA) were depleted by use of an immuno-affinity column, and low-abundance ones were separated into five fractions by anion-exchange chromatography. The fractionated plasma proteins were subjected to 2D-DIGE with highly sensitive fluorescent dyes. The quantitative protein expression profiles obtained by 2D-DIGE were compared between two plasma protein mixtures: one from five non-cancer bearing healthy donors and the other from five patients with pancreatic cancer. Among 1200 protein spots, we found that 33 protein spots were differently expressed between the two mixtures; 27 of these were up-regulated and six were down-regulated in cancer. Mass spectrometry and database searching allowed the identification of the proteins corresponding to the gel spots. Up-regulation of leucine-rich alpha-2-glycoprotein (LRG), which has not previously been implicated in pancreatic cancer, was observed. Western blotting with an anti-LRG antibody validated the up-regulation of LRG in an independent series of plasma samples from healthy controls, patients with chronic pancreatitis, and patients with pancreatic cancer. Our results demonstrate the application of a combination of multi-dimensional liquid chromatography with 2D-DIGE for plasma proteomics and suggest the clinical utility of LRG plasma level measurement. (C) 2007 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jchromb.2007.01.029

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

The poor prognosis of patients with hepatocellular carcinoma (HCC) is attributed to intrahepatic recurrence. To understand the molecular background of early intrahepatic recurrence, we conducted a global protein expression study. We compared the protein expression profiles of the primary HCC tissues of 12 patients who showed intrahepatic recurrence within 6 months post surgery with those of 15 patients who had no recurrence 2 years post surgery. Two-dimensional difference gel electrophoresis identified 23 protein spots, the intensity of which was highly associated with early intrahepatic recurrence. To validate the prediction performance of the identified proteins, we examined additional HCC tissues from 13 HCC patients; six with early intrahepatic recurrence and seven without recurrence. We found that all but one of the 13 patients were grouped according to their recurrence status based on the intensity of the 23 protein spots. Mass spectrometry identified 23 proteins corresponding to the spots. Although 13 of 23 have been previously reported to be correlated with HCC, their association with early intrahepatic recurrence had not been established. The identified proteins are involved in signal transduction pathways, glucose metabolism, cytoskeletal structure, cell adhesion, or function as antioxidants and chaperones. The identified proteins may be candidates for prognostic markers and contribute to the improvement of existing therapeutic strategies.

DOI： 10.1111/j.1349-7006.2007.00441.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

Purpose: We aimed to identify candidate proteins for tumor markers to predict the response to gefitinib treatment.
Experimental Design: We did two-dimensional difference gel electrophoresis to create the protein expression profile of lung adenocarcinoma tissues from patients who showed a different response to gefitinib treatment. We used a support vector machine algorithm to select the proteins that best distinguished 31 responders from 16 nonresponders. The prediction performance of the selected spots was validated by an external sample set, including six responders and eight nonresponders. The results were validated using specific antibodies.
Results: We selected nine proteins that distinguish responders from nonresponders. The predictive performance of the nine proteins was validated examining an additional six responders and eight nonresponders, resulting in positive and negative predictive values of 100% (six of six) and 87.5% (seven of eight), respectively. The differential expression of one of the nine proteins, heart-type fatty acid-binding protein, was successfully validated by ELISA. We also identified 12 proteins as a signature to distinguish tumors based on their epidermal growth factor receptor gene mutation status.
Conclusions: Study of these proteins may contribute to the development of personalized therapy for lung cancer patients.

DOI： 10.1158/1078-0432.CCR-06-1654

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

This case is a 56-year old woman. Steroids were being administered perorally after a thymectomy for myasthenia gravis. A fever of 38-39 degrees Celsius appeared during night, an abnormal shadow showed up on a chest X-ray and the patient was hospitalized. Gaffky No. 2 acid-fast bacilli were detected in the patient's sputum and the chest CT showed diffuse granular-like shadow, the patient was diagnosed as miliary tuberculosis and treatment with combined use of INH, RFP, EB, and PZA was started. Subsequently, fever started to subside and the miliary shadow on chest X-ray improved, however, six weeks after the start of treatment, hoarseness and dysphagia appeared. From the cervical CT and cervical angiography findings, the diagnosis of right subclavian artery impending ruptured aneurysm was made. Because the patient's sputum was acid-fast bacilli positive and because the patient had undergone thymectomy, it was decided that it would be difficult to treat her by a thoracotomy again. Therefore, a right subclavian artery stent insertion, right subclavian artery-right common carotid artery bypass creation operation was carried out with the objective of blocking the flow of blood to the aneurysm. The hoarseness and dysphagia im- proved post-operatively and the patient's progress is being monitored. Tuberculous aneurysms are a rare affection and they are mostly discovered when the autopsy is done, however, this case was diagnosed due to the manifestation of subjective symptoms. While this case was not diagnosed histopathologically, it is envisaged from the clinical progress that this was a tuberculous subclavian aneurysm complicated during the treatment for miliary tuberculosis.

DOI： 10.11400/kekkaku1923.82.111

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Phase III trials evaluating the efficacy of gefitinib (IRESSA) in non-small cell lung cancer (NSCLC) lend support to the need for improved patient selection in terms of gefitinib use. Mutation of the epidermal growth factor receptor (EGFR) gene is reported to be associated with clinical responsiveness to gefitinib. However, gefitinib-sensitive and prolonged stable-disease-defined tumors without EGFR gene mutation have also been reported.
Methods: To identify other key factors involved in gefitinib sensitivity, we analyzed the protein expression of molecules within the EGFR family, PI3K-Akt and Ras/MEK/Erk pathways and examined the sensitivity to gefitinib using the MTT cell proliferation assay in 23 lung cancer cell lines.
Results: We identified one highly sensitive cell line (PC9), eight cell lines displaying intermediate-sensitivity, and 14 resistant cell lines. Only PC9 and PC14 (intermediate-sensitivity) displayed an EGFR gene mutation including amplification. Eight out of the nine cell lines showing sensitivity had Akt phosphorylation without ligand stimulation, while only three out of the 14 resistant lines displayed this characteristic (P = 0.0059). Furthermore, the ratio of phosphor-Akt/total Akt in sensitive cells was higher than that observed in resistant cells (P = 0.0016). Akt phosphorylation was partially inhibited by gefitinib in all sensitive cell lines.
Conclusion: These results suggest that Akt phosphorylation without ligand stimulation may play a key signaling role in gefitinib sensitivity, especially intermediate-sensitivity. In addition, expression analyses of the EGFR family, EGFR gene mutation, and FISH (fluorescence in situ hybridization) analyses showed that the phosphorylated state of EGFR and Akt might be a useful clinical marker of Akt activation without ligand stimulation, in addition to EGFR gene mutation and amplification, particularly in adenocarcinomas.

DOI： 10.1186/1471-2407-6-277

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT INST ANTICANCER RESEARCH  

A gene-drug correlation analysis was previously performed in lung cancer cell lines using the NC160 program. On the basis of this work, a phase I/II pilot study of weekly paclitaxel and carboplatin (CBDCA) was subsequently planned for refractory or recurrent non-small cell lung cancer (NSCLC). Safety and antitumor effects were evaluable in all 30 patients registered for this study. Seven patients were stage IIIB and 23 were stage IV. At level 5 (paclitaxel 100 mg/m(2) and CBDCA AUC5), toxicities were not dose-limiting factors, but three out of the initial six cases had infusion skips. Our recommended dose was paclitaxel 100 mg/m(2) and CBDCA AUC5. The response rate was 50% (9118)(95% CI: 27-73%) in step 5. The median survival time was 12 months. This combination showed a promising clinical activity with mild toxicity and should be selected for the investigational arm of phase III trials to be compared with either docetaxel or pemetrexed.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-V C H VERLAG GMBH  

To investigate aberrant plasma proteins in lung cancer, we compared the proteomic profiles of serum from five lung cancer patients and from four healthy volunteers. Immuno-affinity chromatography was used to deplete highly abundant plasma proteins, and the resulting plasma samples were separated into eight fractions by anion-exchange chromatography. Quantitative protein profiles of the fractionated samples were generated by two-dimensional difference gel electrophoresis, in which the experimental samples and the internal control samples were labeled with different dyes and co-separated by two-dimensional polyacrylamide gel electrophoresis. This approach succeeded in resolving 3890 protein spots. For 364 of the protein spots, the expression level in lung cancer was more than twofold different from that in the healthy volunteers. These differences were statistically significant (Student's t-test, p-value less than 0.05). Mass spectrometric protein identification revealed that the 364 protein spots corresponded to 58 gene products, including the classical plasma proteins and the tissue-leakage proteins catalase, clusterin, ficolin, gelsolin, lumican, tetranectin, triosephosphate isomerase and vitronectin. The combination of multi-dimensional liquid chromatography and two-dimensional difference gel electrophoresis provides a valuable tool for serum proteomics in lung cancer.

DOI： 10.1002/pmic.200500883

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-V C H VERLAG GMBH  

CyDye DIGE Fluor saturation dye (saturation dye, GE Healthcare Amersham Biosciences) enables highly sensitive 2-D PAGE. As the dye reacts with all reduced cysteine thiols, 2-D PAGE can be performed with a lower amount of protein, compared with CyDye DIGE Fluor minimal dye (GE Healthcare Amersham Biosciences), the sensitivity of which is equivalent to that of silver staining. We constructed a 2-D map of the saturation dye-labeled proteins of a liver cancer cell line (HepG2) and identified by MS 92 proteins corresponding to 123 protein spots. Functional classification revealed that the identified proteins had chaperone, protein binding, nucleotide binding, metal ion binding, isomerase activity and motor activity. The functional distribution and the cysteine contents of the proteins were similar to those in the most comprehensive 2-D database of hepatoma cells (Seow et al., Electrophoresis 2000, 21, 1787-1813), where silver staining was used for protein visualization. Hierarchical clustering on the basis of the quantitative expression profiles of the 123 characterized spots labeled with two charge- and mass-matched saturation dyes (Cy3 and Cy5) discriminated between nine hepatocellular carcinoma cell lines and primary cultured hepatocytes from five individuals, suggesting the utility of saturation dye and our database for proteomic studies of liver cancer.

DOI： 10.1002/pmic.200401346

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

The ING1 gene is involved in the regulation of the cell cycle, senescence, and apoptosis and is a novel candidate tumor suppressor gene. ING2, another gene in the ING family, was identified and cloned. The functions of ING1 and ING2 largely depend on the activity of p53. To determine whether an alteration in these genes plays a role in carcinogenesis and tumor progression in lung cancer, we screened 30 human lung cancer cell lines and 31 primary lung cancer tumors for mutations in these genes using polymerase chain reaction-single strand conformation polymorphism (PCRSSCP) and direct sequencing. Our findings failed to uncover any mutations in these genes. We also examined the expression of ING1 and ING2 in lung cancer cell lines that either had or lacked a p53 mutation, and in a control bronchial epithelium cell line, using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). ING1 expression was up-regulated in all 7 lung cancer cell lines that had a p53 mutation, while the expression of ING2 was down-regulated in 6 of 7 lung cancer cell lines that had a p53 mutation. These results suggest that the ING1 and ING2 genes have different roles in lung carcinogenesis and progression, and the ING2 gene may be an independent tumor suppressor candidate on p53.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-V C H VERLAG GMBH  

We performed proteomic studies on lung cancer cells to elucidate the mechanisms that determine histological phenotype. Thirty lung cancer cell lines with three different histological backgrounds (squamous cell carcinoma, small cell lung carcinoma and adenocarcinoma) were subjected to two-dimensional difference gel electrophoresis (2-D DIGE) and grouped by multivariate analyses on the basis of their protein expression profiles. 2-D DIGE achieves more accurate quantification of protein expression by using highly sensitive fluorescence dyes to label the cysteine residues of proteins prior to two-dimensional polyacrylamide gel electrophoresis. We found that hierarchical clustering analysis and principal component analysis divided the cell lines according to their original histology. Spot ranking analysis using a support vector machine algorithm and unsupervised classification methods identified 32 protein spots essential for the classification. The proteins corresponding to the spots were identified by mass spectrometry. Next, lung cancer cells isolated from tumor tissue by laser microdissection were classified on the basis of the expression pattern of these 32 protein spots. Based on the expression profile of the 32 spots, the isolated cancer cells were categorized into three histological groups: the squamous cell carcinoma group, the adenocarcinoma group, and a group of carcinomas with other histological types. In conclusion, our results demonstrate the utility of quantitative proteomic analysis for molecular diagnosis and classification of lung cancer cells.

DOI： 10.1002/pmic.200401166

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Gefitinib (IRESSA), an epidermal growth factor receptor ( EGFR) tyrosine kinase (TK) inhibitor, has antitumour activity in the advanced non-small-cell lung cancer (NSCLC) setting. However, in chemotherapy-naive patients with advanced NSCLC, the addition of gefitinib to standard chemotherapy regimens failed to increase survival. These results suggest the need for improved patient selection and combination rationales for targeted therapies. We have identified subpopulations of an adenocarcinoma cell line that are naturally resistant to gefitinib, and have analysed the cDNA expression profiles, genomic status of EGFR gene and the effect of gefitinib on signalling pathways in these cell lines in order to identify key mechanisms for naturally acquired resistance to gefitinib. Gefitinib-resistant subpopulations demonstrated increased Akt phosphorylation ( not inhibited by gefitinib), reduced PTEN protein expression and loss of the EGFR gene mutation when compared with parental cell lines. These differences in Akt and PTEN protein expression were not evident from the cDNA array profiles. These data suggests that ( 1) the EGFR gene mutation may be possibly lost in some cancer cells with other additional mechanisms for activating Akt, ( 2) reintroduction of PTEN or pharmacological downregulation of the constitutive PI3K - Akt-pathway activity may be an attractive therapeutic strategy in cancers with gefitinib resistance.

DOI： 10.1038/sj.bjc.6602559

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

Purpose: Weekly administrations of CPT-11 plus cisplatin together with an anti-diarrheal. program, the Oral Alkalization and Control of Defecation [Int J Cancer 1999;83:491; Int J Cancer 2001;92:269; Cancer Res 2002;62:179], were evaluated in this phase II study for patients with refractory or relapsed small cell lung cancer. Methods: Patients were treated by weekly administrations of 60 mg/m(2) CPT-11 plus 30 mg/m(2) cisplatin on Days 1, 8 and 15 over 4 weeks. Coinciding with the infusions and for 4 days thereafter, the anti-diarrheal program was practiced using orally administered sodium bicarbonate, magnesium oxide and basic water. Results: Twenty-five patients who had prior treatments of etoposide and platinum containing regimens (16 refractory patients and nine relapsed patients) were entered. The mean dose-intensities of CPT-11 and cisplatin were 154.8 and 77.4 mg/m(2) per course, respectively. Therefore, 86% of the planned dose, was delivered. There were 20 partial responses and an overall response rate of 80% (95% confidence interval, 62-96%) was obtained. The median time to progression and the median survival after starting this regimen were 3.6 and 7.9 months, respectively. The major toxicity was myelosuppression. Grades 3 and 4 neutropenia occurred in 24 and 12% of patients, respectively. One patient with febrile neutropenia was experienced, and Grade 3 diarrhea was observed in 8%. But there was no treatment death. Conclusion: Weekly administrations of CPT-11 plus cisplatin together with Oral Alkalization and Control of Defecation provide a practical and well tolerated regimen that was active for refractory or relapsed small cell lung cancer. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.lungstan.2003.10.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

Reduced expression of the retinoblastoma gene (RB)2/p130 protein, as well as mutation of exons 19, 20, 21, and 22 of the same gene, has been reported in primary lung cancer. However, it has been suggested by other investigators that mutational inactivation and loss of the RB2/p130 gene and protein, respectively, are rare events in lung cancer. In order to determine the contribution and mechanisms of RB2/p130 gene inactivation to lung cancer development and progression, we quantified RB2/p130 mRNA expression levels in a range of human lung cancer cell lines (n=13) by real-time reverse transcription (RT)-polymerase chain reaction (PCR) analysis. In comparison to normal lung tissue, reduced transcription of the RB2/p130 gene was found in all small cell lung cancer cell lines examined, along with six out of the eight nonsmall cell lung cancers tested, most of which had inactivation of RB/p16 pathway. On the basis of Western blot analysis, the expression of RB2/p130 protein was consistent with RNA expression levels in all lung cancer cell lines examined. In addition, the mutational status of the RB2/p130 gene (specifically, exons 19, 20, 21, and 22) was determined in 30 primary lung cancers (from patients with distant metastasis) and 30 lung cancer cell lines by PCR-single strand conformation polymorphism (SSCP) analysis and direct DNA sequencing. There was no evidence of somatic mutations within the RB2/p130 gene in the 60 lung cancer samples (both cell lines and tumors) assessed, including the 11 lung cancer cell lines that displayed reduced expression of the gene. Furthermore, hypermethylation of the RB2/p130 promoter was not found in any of the above-mentioned 11 cell lines, as determined by a DNA methylation assay, combined bisulfite restriction analysis (COBRA). The results of the present study suggest that the reduced RB2/p130 expression seen in lung cancer may be in part transcriptionally mediated, albeit not likely via a mechanism involving hypermethylation of the RB2/p130 promoter. The observed reduction in RB2/p130 gene expression may be due to histone deacetylation, altered mRNA stability, and/or other forms of transcriptional regulation. (C) 2003 Wiley-Liss, Inc.

DOI： 10.1002/mc.10152

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

Using cDNA array-based gene expression profiling, we previously found reduced expression of the Caspase-5 gene in highly metastatic subpopulations of a lung cancer cell line. The Caspase-5 gene contained poly(A) repeats in its coding region, an area that has been reported to be mutated in both endometrial and gastrointestinal tumors displaying evidence of microsatellite instability. In order to determine the contribution of Caspase-5 gene inactivation to lung cancer development and progression, the mutational status of the Caspase-5 poly(A) tract in 30 primary lung cancers with distant metastasis and 30 lung cancer cell lines was determined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. Three somatic mutations of the Caspase-5 gene were found in two out of 30 lung cancer tissues, although no mutations were found in other genes that also contain small nucleotide repeats, such as hMSH3, hMSH6 and BAX. The results of the present study, combined with our prior cDNA array-based gene expression profiling data, suggest that Caspase-5 might be a suppressor gene of highly metastatic potential in lung cancer.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

Patients with lung cancer have a poor prognosis because of the high metastatic potential of the neoplasm. Therefore, identifying new molecular targets for anti-metastatic therapy is very important. To identify novel key factors of tumor metastasis in lung cancer, we established the gene expression profiles of two adenocarcinoma cell line variants, PC9/f9 and PC9/f14, by use of genome-wide human cDNA microarray analysis and comparing these profiles with that of the parental cell line, PC9. The PC9/f9 and PC9/f14 cell lines were selected for analysis because of their high metastatic potential. We identified five genes in the highly metastatic cell lines that showed a significantly enhanced or reduced expression and that had not been reported to be involved in metastasis of lung cancer. One of the overexpressed genes that was identified encoded the beta-galactoside-binding protein LGALS3 (Galectin 3). LGALS3 has been reported to be overexpressed in a variety of human cancers, but not in lung cancer, and to be involved in tumor metastasis. We examined the expression of LGALS3 by use of real-time quantitative reverse transcription-polymerase chain reaction in 38 lung cancer cell lines and in tumor tissue obtained by thoracoscopic biopsy. A population (10130) of the non-small-cell lung cancers examined was found to overexpress the LGALS3 gene at levels three times higher than those of normal epithelial cells. In contrast, all small-cell lung cancers either failed to express the gene or expressed it at a very low level. The mean of the relative expression of the LGALS3 gene in nonsmall-cell lung cancer (3.065 +/- 3.976) was significantly higher than those of small-cell lung cancer (0.02 +/- 0.03) (P &lt; 0.025). This is the first report of alterations of LGALS3 gene expression in lung cancer. These results, together with the previous reports on Galectin 3 function, suggest that Galectin 3 may play a role in the process of metastasis in non-small-cell lung cancer that overexpresses Galectin 3, but not in small-cell cancer. Accordingly, LGALS3 may be a phenotypic marker that excludes small-cell lung cancer and may represent a novel target molecule in non-small-cell lung cancer therapy. (C) 2003 Wiley-Liss, Inc.

DOI： 10.1002/gcc.10205

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

Mitotic checkpoint impairment is present in human lung cancers with chromosomal instability (CIN). Spindle-checkpoint genes have been reported to be mutated in several human cancers; but these mutations are infrequent. Recent reports suggest that the hBUBR1 gene may play an important role in mitotic checkpoint control and in mitotic checkpoint impairment in human cancers. We analyzed the expression of hBUBR1 in lung cancer cell lines using real time quantitative RT-PCR. The expression of BUBR1 was found to be up-regulated in all of these cell lines. In addition, we cloned and characterized the promotor region of hBUBR1 and determined its genomic structure, which includes 23 exons. The open reading frame (ORF) of the hBUBR1 gene comprises exons 1 through 23. There are GC-rich regions located at the flanking region and about 150 bp upstream from exon 1. The promoter region (424 bp upstream from exon 1) showed promoter activity and includes multiple transcription factor consensus binding motifs, including those for Sp1, Nkx-2, CdxA, SRY, MyoD, Ik-2, HNF-3b, Staf, Oct-1, Nkx-2, v-Myb, and AML 1a. Multiple pathways leading to activation of those binding factors may contribute to hBUBR1 gene transcription. Knowledge of the genomic structure and the promoter region of the hBUBR1 gene will facilitate investigation of its role in mitotic checkpoint control and tumor progression in human cancers. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/s0169-5002(02)00218-0

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器外科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器外科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器外科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：英語   出版者・発行元：東京医科大学医学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：日本胸部外科学会-関東甲信越地方会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：英語   出版者・発行元：東京医科大学医学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：日本胸部外科学会-関東甲信越地方会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本レーザー医学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器外科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

DOI： 10.2482/haigan.57.875

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器外科学会  

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記述言語：日本語   出版者・発行元：日本胸部外科学会-関東甲信越地方会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCIENCE INC  

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記述言語：日本語   出版者・発行元：東京医科大学医学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCIENCE INC  

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記述言語：英語   出版者・発行元：東京医科大学医学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCIENCE INC  

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記述言語：日本語  

DOI： 10.2482/haigan.57.875

J-GLOBAL

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

肺動脈内膜肉腫は稀な疾患であり、外科的切除を行わない場合の予後は1.5ヵ月程度と極めて不良である。臨床症状や画像所見からは肺塞栓症との鑑別に苦慮することが多い。今回我々は慢性血栓塞栓性肺高血圧症が疑われた肺動脈内膜肉腫の1例を経験したため報告する。(著者抄録)

DOI： 10.2482/haigan.57.875

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：日本電気泳動学会  

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記述言語：英語   出版者・発行元：東京医科大学医学会  

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記述言語：日本語   出版者・発行元：日本胸部外科学会-関東甲信越地方会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器外科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器外科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器外科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器外科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器外科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：日本臨床プロテオーム研究会  

DOI： 10.14905/jscp.2014.0_13

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

DOI： 10.1111/resp.12184_14

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記述言語：日本語   出版者・発行元：(公財)日本心臓財団  

2007年4月〜2012年3月の原発性肺癌1953例のうち、肺動脈血栓塞栓症(PTE)を合併した18例(男11例、女7例、平均年齢66.4歳)の臨床的特徴を後方視的に検討した。組織型は腺癌が15例、扁平上皮癌・小細胞癌・その他の非小細胞肺癌が各1例ずつであった。病期はstage I〜IIIAが4例、stage IIIBが3例、stage IVが11例であった。発症時の自覚症状は呼吸困難6例、下腿浮腫3例、酸素飽和度低下2例、顔面・頸部の浮腫2例であったが、無症状も5例存在した。EGFR遺伝子変異の解析結果9例が陽性であり、Fisherの正確確率検定ではEGFR変異陽性例で有意にPTE合併が多かった。11例の死亡が確認され、直接死因がPTEであったものは1例、肺癌が9例であった。

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J00679&link_issn=&doc_id=20130718330037&doc_link_id=%2Fah2sinzd%2F2013%2F004507%2F039%2F0869-0871%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fah2sinzd%2F2013%2F004507%2F039%2F0869-0871%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：英語  

Background: Enzastaurin, an oral serine-threonine kinase inhibitor, was initially developed as an ATP-competitive selective inhibitor against protein kinase CΒ. However, the mechanism by which enzastaurin contributes to tumourigenesis remains unclear. Methods: We analysed the anti-tumour effects of enzastaurin in 22 lung cancer cell lines to ascertain the potential for enzastaurin-based treatment of lung cancer. To identify molecules or signalling pathways associated with this sensitivity, we conducted a gene, receptor tyrosine kinases phosphorylation and microRNA expression profiling study on the same set of cell lines.Results:We identified eight genes by pathway analysis of molecules having gene-drug sensitivity correlation, and used them to build a support vector machine algorithm model by which sensitive cell lines were distinguished from resistant cell lines. Pathway analysis revealed that the JAK/STAT signalling pathway was one of the main ones involved in sensitivity to enzastaurin. Overexpression of JAK1 was observed in the sensitive cells by western blotting. Simultaneous administration of enzastaurin and JAK inhibitor inhibited enzastaurin-induced cell growth-inhibitory effect. Furthermore, lentiviral-mediated JAK1-overexpressing cells were more sensitive to enzastaurin than control cells. Conclusion: Our results suggested that the JAK1 pathway may be used as a single predictive biomarker for enzastaurin treatment. The anti-tumour effect of enzastaurin should be evaluated in lung cancer with overexpressed JAK pathway molecules. © 2012 Cancer Research UK All rights reserved.

DOI： 10.1038/bjc.2012.7

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

DOI： 10.1272/manms.6.211

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(公社)東京都臨床検査技師会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM10-3606

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(公社)東京都臨床検査技師会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(株)自然科学社  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(株)総合医学社  

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記述言語：日本語   出版者・発行元：日本臨床プロテオーム研究会  

DOI： 10.14905/jscp.2008.0_3

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記述言語：日本語   出版者・発行元：日本臨床プロテオーム研究会  

DOI： 10.14905/jscp.2008.0_16

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：BLACKWELL PUBLISHING  

Web of Science

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

J-GLOBAL

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.29.4_261_6

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：日本臨床プロテオーム研究会  

【背景】間質性肺炎には高頻度に肺癌が合併することが知られており、その発癌機序、生物学特徴を明らかにすることが予防、治療の上で不可欠と考えられる。TGFβは本症において恒常的に発現が亢進しており、癌化と密接に関わっている可能性がある。また、TGFβによるEpithelial to mesenchymal transition (EMT)は浸潤、転移にも深く関わっている。【目的】肺癌細胞株を用いてTGFβ曝露下での細胞シグナルの変化から間質性肺炎合併肺癌の癌化、浸潤・転移のメカニズムを明らかにする。【方法】我々は、肺癌細胞株A549,Calu-6,SK-Lu 1,VMRC-LCD,IP-LKM（当科樹立間質性肺炎合併肺癌細胞株）をｈTGFβ1曝露下における細胞形態変化、細胞増殖能変化（MTT assay）でスクリーニングし、TGFβ感受性株について、TGFβによるその発現プロファイルの変化をcDNAアレイ、抗体アレイ、二次元電気泳動（２D-DIGE）にて確認した。【結果】肺腺癌細胞株A549は、ｈTGFβ1添加により著明に細胞増殖が抑制され、細胞形態的にEMTを示した。ウエスタンブロットにて上皮系マーカーの低下、間葉系マーカーの上昇を認め、EMTを確認した。抗体アレイの解析では、TGFβ添加により4タンパク質の発現亢進と４タンパク質の発現低下が認められた。また、２D-DIGEによる約2000のタンパク質スポットの発現解析では53のタンパク質の優位な発現変化を認めた。今後、これらの情報を基に機能解析を施行する予定である。

DOI： 10.14905/jscp.2007.0.2.0

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記述言語：日本語   出版者・発行元：日本臨床プロテオーム研究会  

【目的】肺癌治療の成績向上に化学療法の果たす役割が期待されているが、効果は十分なものとは言えず、その原因として抗癌剤耐性化や不応症例の問題が考えられる。今回、肺癌細胞株を用いたプロテオーム解析にて、新規抗癌剤の一つであるジェムシタビンについて感受性因子の検索を試みた。【方法と結果】ジェムシタビン感受性である肺腺癌細胞株PC9と当科で樹立したジェムシタビン耐性を有する高転移株PC9/f14の２つの株で、224の抗体を用いたAntibody arrayによりタンパク質発現プロファイルを作成し、薬剤感受性因子のスクリーニングを行った。Antibody array 解析において、ジェムシタビン暴露後に感受性株ではCalponinの発現上昇を認め、一方、耐性株においてはBcl-Xタンパク質の発現亢進が認められた。次にジェムシタビン暴露後のapoptosis誘導についてFlow CytometryとTunnel法を用いて解析を行った。感受性株のPC9と比べて耐性株のPC9/f14においては、Flow CytometryとTunnel法のいずれにおいても明らかにapoptosis誘導が抑えられていた。さらに耐性株においてBcl-X遺伝子発現をsiRNAにて抑制することでapoptosis誘導がなされ、ジェムシタビン感受性の改善が示されるかについて検討した。その結果、耐性株PC9/f14でBcl-X発現を抑制すると明らかにジェムシタビンの感受性が改善を示した。【結語】今回の解析でBcl-Xタンパク質の発現異常が、ジェムシタビン感受性に関わる因子一つである可能性が示唆された。

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Web of Science

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記述言語：日本語   出版者・発行元：日本癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

「かぜ症候群」は日常診療でもっとも多く診察する病気である.その大部分は1週間以内に軽快するが,咳嗽,喀痰などの下気道症状が加わると,肺癌などの呼吸器疾患との鑑別が必要となる.肺癌の発見動機は,咳嗽,胸痛,全身倦怠感などの「かぜ症候群」とほぼ同様の症状である.持続する咳嗽や血痰,胸痛,呼吸困難などが認められる場合,喀痰検査や胸部X線撮影を行うべきである.肺癌の原因として喫煙が最大のものであるが,最近注目を集めているものとしてアスベストの職業環境曝露がある.他に肺線維症などの呼吸器の既存疾患があげられる.肺癌の危険因子が高い症例では,肺癌の合併に注意し,上記検査が必要である.胸部X線写真による肺癌の検出感度は80%程度といわれているが,肺門部の早期肺癌のように末梢に二次性変化を起こさない限り,胸部X線像に異常陰影を示さない場合もあり,3日間連続採痰による喀痰細胞診を行うことが重要である.また,境界不明瞭で淡く小さな陰影や既存構造との重なりによりX線写真に抽出されているにもかかわらず,検出できないで見落とされる場合もあり,CT検査も考慮されるべきである(著者抄録)

CiNii Books

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.28.1_71_3

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：日本肺癌学会  

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記述言語：日本語   出版者・発行元：日本肺癌学会  

CiNii Books

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記述言語：日本語   出版者・発行元：日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Web of Science

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記述言語：英語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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出版者・発行元：日本プロテオーム学会（日本ヒトプロテオーム機構）  

【背景】膵がんは早期発見が困難であるため手術不能例が多く予後不良な疾患である。早期に膵がんを診断できる鋭敏かつ特異的な腫瘍マーカーが求められている。本研究では膵がん患者の血漿を用い，プロテオーム解析の手法によって，膵がんにおいて発現ならびに翻訳後修飾の異常が認められる血漿タンパク質群を同定した。<BR>【方法】国立がんセンター中央病院を受診した膵がん患者の血漿（n = 5）とボランティアの血漿（n = 5）を使用した。Multiple Affinity Removal Column（Agilent社）を用い，血漿から高容量タンパク質を取り除き低容量タンパク質画分（FT）を得た。 さらにFTを陰イオン交換カラムで5画分に分けた。全血漿，FTは個々人のサンプルで二次元電気泳動を行い，陰イオン交換カラムで分けたサンプルはそれぞれの分画で膵がん患者，ボランティアごとに混合し，二次元電気泳動を行った。二次元電気泳動の方法としては，2D-DIGE（two-dimensional difference gel electrophoresis）法を用いた。膵がん患者とボランティアで2倍以上発現量が変化しているスポットを，画像解析ソフトを用いて検索した。統計学的手法はStudent's t-testを使用し，p<0.01を有意とした。有意に発現量が変化しているスポットは質量分析にてタンパク質を同定した。<BR>【結果】全血漿の二次元電気泳動では290スポットが観察されたが，高容量タンパク質を除いたFTでは403スポットに増加した。さらに陰イオン交換カラムを使用することで観察可能なタンパク質が合計1098スポットに増加した。この増加は分画によりタンパク質サンプルの複雑度を減少させたことによるものと考えられる。膵がん患者において有意に発現量が変化しているスポットが39スポット同定され，質量分析にてタンパク質を同定した。<BR>【結論】多次元液体クロマトグラフィーと二次元電気泳動法を組み合わせた手法は血漿のプロテオーム解析において有効な方法である。同定されたタンパク質は膵がんの腫瘍マーカーとして有用なだけでなく，膵がんの病態の理解にもつながる可能性がある。

DOI： 10.14889/jhupo.2005.0.137.0

CiNii Research

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記述言語：英語   出版者・発行元：日本肺癌学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Web of Science

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記述言語：英語   出版者・発行元：(NPO)日本肺癌学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2004&ichushi_jid=J01244&link_issn=&doc_id=20041006270712&doc_link_id=%2Fec7jaluc%2F2004%2F004405%2F712%2F0659-0659%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fec7jaluc%2F2004%2F004405%2F712%2F0659-0659%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   出版者・発行元：(NPO)日本肺癌学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2004&ichushi_jid=J01244&link_issn=&doc_id=20041006270696&doc_link_id=%2Fec7jaluc%2F2004%2F004405%2F696%2F0651-0651%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fec7jaluc%2F2004%2F004405%2F696%2F0651-0651%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Web of Science

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記述言語：日本語   出版者・発行元：日本癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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Cancer is the leading cause of disease death in Japan. Despite recent progress of early diagnostic modalities and therapeutic management, the long-term survival of cancer patients has been still poor and the extensive efforts to improve the prognosis have been devoted to cancer research. To identify the proteins associated with various clinical states of cancer and to utilize such proteins as diagnostic and prognostic biomarkers, we established the proteome analysis system based on two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and bioinformatics approach. In our system, the quantitative protein expression profiles are generated by two-dimensional difference gel electrophoresis (2D-DIGE), in which protein samples are labeled with fluorescence dyes prior to 2D-PAGE. As high sensitive fluorescent dyes enable high-throughput laser microdissection, 2D-DIGE can achieve accurate clinical proteomic study. Multivariate algorithms and statistical-learning methods determine unique protein expression patterns corresponding to clinical features and mass spectrometric study identifies the proteins involved in the patterns. Proteomic study using cancer cell lines and clinical specimens of various types of cancer revealed that our proteome analysis system can identify the protein expression patters corresponding to 1) original organ and histology, 2) properties of metastasis and invasion, or 3) histological subtype of malignancies.

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記述言語：日本語   出版者・発行元：日本肺癌学会  

CiNii Books

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

CiNii Books

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2003&ichushi_jid=J01244&link_issn=&doc_id=20031023340095&doc_link_id=%2Fec7jaluc%2F2003%2F004305%2F095%2F0480-0480%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fec7jaluc%2F2003%2F004305%2F095%2F0480-0480%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(株)中外医学社  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：英語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本結核病学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(株)篠原出版新社  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本肺癌学会  

CiNii Books

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

化学療法後23例中2例,外科療法後14例中2例,放射線療法後8例中2例にIIPの急性増悪が認められた.治療前の血清CRP値が,急性増悪群は5.12±2.27mg/dl,非増悪群は2.26±2.29mg/dlで急性増悪群が有意に高値であった.一方,ESR,LDH,WBC,PaO2,%VCには有意差は認められなかった.組織学的評価で,急性増悪例と非増悪例に明らかな差は認められなかったが,急性増悪例に組織学的に活動性と思われる症例が存在した.急性増悪した6例中5例は3ヵ月以内に死亡した.IIP合併肺癌症例の肺癌治療は,新しいマーカーや経気管支肺生検などを用い,IIPの活動性のより正確な評価の上に行うべきと考えられた

DOI： 10.2482/haigan.39.955

CiNii Books

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER LUNG ASSOC  

Web of Science

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記述言語：日本語   出版者・発行元：日本肺癌学会  

CiNii Books

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

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記述言語：日本語   出版者・発行元：日本肺癌学会  

CiNii Books

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記述言語：日本語   出版者・発行元：日本肺癌学会  

CiNii Books

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開催年月日： 2021年10月

記述言語：英語  

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開催年月日： 2021年4月

記述言語：日本語  

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開催年月日： 2021年4月

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開催年月日： 2021年4月

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開催年月日： 2021年4月

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開催年月日： 2021年4月

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開催年月日： 2021年4月

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開催年月日： 2021年2月

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開催年月日： 2020年9月

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開催年月日： 2020年2月

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開催年月日： 2019年6月

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開催年月日： 2019年6月

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開催年月日： 2019年6月

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開催年月日： 2018年10月

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開催年月日： 2018年7月

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開催年月日： 2018年7月

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開催年月日： 2018年7月

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開催年月日： 2018年5月

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開催年月日： 2018年5月

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開催年月日： 2018年4月

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開催年月日： 2018年3月

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開催年月日： 2018年2月

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開催年月日： 2018年1月

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開催年月日： 2018年1月

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開催年月日： 2017年11月

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開催年月日： 2017年11月

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開催年月日： 2017年11月

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開催年月日： 2017年10月

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開催年月日： 2017年9月

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開催年月日： 2017年9月

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開催年月日： 2017年9月

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開催年月日： 2017年9月

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開催年月日： 2017年9月

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開催年月日： 2017年5月

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開催年月日： 2017年5月

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開催年月日： 2017年5月

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開催年月日： 2017年5月

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開催年月日： 2017年5月

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開催年月日： 2017年5月

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開催年月日： 2017年5月

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開催年月日： 2017年5月

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開催年月日： 2017年5月

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開催年月日： 2017年5月

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開催年月日： 2017年4月

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開催年月日： 2017年4月

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開催年月日： 2017年4月

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開催年月日： 2017年3月

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開催年月日： 2017年2月

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開催年月日： 2017年1月

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開催年月日： 2017年1月

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開催年月日： 2017年1月

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開催年月日： 2017年1月

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開催年月日： 2017年

記述言語：日本語  

肺動脈内膜肉腫は稀な疾患であり、外科的切除を行わない場合の予後は1.5ヵ月程度と極めて不良である。臨床症状や画像所見からは肺塞栓症との鑑別に苦慮することが多い。今回我々は慢性血栓塞栓性肺高血圧症が疑われた肺動脈内膜肉腫の1例を経験したため報告する。(著者抄録)

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開催年月日： 2016年4月

記述言語：日本語  

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開催年月日： 2016年4月

記述言語：日本語  

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開催年月日： 2016年4月

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開催年月日： 2016年2月

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開催年月日： 2016年1月

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開催年月日： 2016年

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開催年月日： 2016年

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開催年月日： 2014年12月

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開催年月日： 2014年3月

記述言語：英語  

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開催年月日： 2014年

記述言語：日本語  

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開催年月日： 2013年11月

記述言語：英語  

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開催年月日： 2013年7月

記述言語：日本語  

2007年4月〜2012年3月の原発性肺癌1953例のうち、肺動脈血栓塞栓症(PTE)を合併した18例(男11例、女7例、平均年齢66.4歳)の臨床的特徴を後方視的に検討した。組織型は腺癌が15例、扁平上皮癌・小細胞癌・その他の非小細胞肺癌が各1例ずつであった。病期はstage I〜IIIAが4例、stage IIIBが3例、stage IVが11例であった。発症時の自覚症状は呼吸困難6例、下腿浮腫3例、酸素飽和度低下2例、顔面・頸部の浮腫2例であったが、無症状も5例存在した。EGFR遺伝子変異の解析結果9例が陽性であり、Fisherの正確確率検定ではEGFR変異陽性例で有意にPTE合併が多かった。11例の死亡が確認され、直接死因がPTEであったものは1例、肺癌が9例であった。

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J00679&link_issn=&doc_id=20130718330037&doc_link_id=%2Fah2sinzd%2F2013%2F004507%2F039%2F0869-0871%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fah2sinzd%2F2013%2F004507%2F039%2F0869-0871%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

開催年月日： 2013年5月

記述言語：日本語  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J00298&link_issn=&doc_id=20130603320300&doc_link_id=%2Fcf0brond%2F2013%2F0035s1%2F301%2F5227-5227%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcf0brond%2F2013%2F0035s1%2F301%2F5227-5227%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

開催年月日： 2012年10月

記述言語：日本語  

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開催年月日： 2012年10月

記述言語：日本語  

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開催年月日： 2012年3月

記述言語：日本語  

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開催年月日： 2012年2月

記述言語：英語  

Background: Enzastaurin, an oral serine-threonine kinase inhibitor, was initially developed as an ATP-competitive selective inhibitor against protein kinase CΒ. However, the mechanism by which enzastaurin contributes to tumourigenesis remains unclear. Methods: We analysed the anti-tumour effects of enzastaurin in 22 lung cancer cell lines to ascertain the potential for enzastaurin-based treatment of lung cancer. To identify molecules or signalling pathways associated with this sensitivity, we conducted a gene, receptor tyrosine kinases phosphorylation and microRNA expression profiling study on the same set of cell lines.Results:We identified eight genes by pathway analysis of molecules having gene-drug sensitivity correlation, and used them to build a support vector machine algorithm model by which sensitive cell lines were distinguished from resistant cell lines. Pathway analysis revealed that the JAK/STAT signalling pathway was one of the main ones involved in sensitivity to enzastaurin. Overexpression of JAK1 was observed in the sensitive cells by western blotting. Simultaneous administration of enzastaurin and JAK inhibitor inhibited enzastaurin-induced cell growth-inhibitory effect. Furthermore, lentiviral-mediated JAK1-overexpressing cells were more sensitive to enzastaurin than control cells. Conclusion: Our results suggested that the JAK1 pathway may be used as a single predictive biomarker for enzastaurin treatment. The anti-tumour effect of enzastaurin should be evaluated in lung cancer with overexpressed JAK pathway molecules. © 2012 Cancer Research UK All rights reserved.

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開催年月日： 2011年5月

記述言語：日本語  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J00298&link_issn=&doc_id=20110615200210&doc_link_id=%2Fcf0brond%2F2011%2F0033s1%2F213%2F5231-5231%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcf0brond%2F2011%2F0033s1%2F213%2F5231-5231%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

開催年月日： 2010年10月

記述言語：日本語  

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開催年月日： 2010年10月

記述言語：日本語  

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開催年月日： 2010年10月

記述言語：日本語  

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開催年月日： 2010年9月

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開催年月日： 2010年9月

記述言語：日本語  

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開催年月日： 2010年8月

記述言語：日本語  

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開催年月日： 2010年8月

記述言語：英語  

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開催年月日： 2010年

記述言語：日本語  

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開催年月日： 2008年

記述言語：日本語  

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開催年月日： 2007年

記述言語：日本語  

【目的】肺癌治療の成績向上に化学療法の果たす役割が期待されているが、効果は十分なものとは言えず、その原因として抗癌剤耐性化や不応症例の問題が考えられる。今回、肺癌細胞株を用いたプロテオーム解析にて、新規抗癌剤の一つであるジェムシタビンについて感受性因子の検索を試みた。【方法と結果】ジェムシタビン感受性である肺腺癌細胞株PC9と当科で樹立したジェムシタビン耐性を有する高転移株PC9/f14の２つの株で、224の抗体を用いたAntibody arrayによりタンパク質発現プロファイルを作成し、薬剤感受性因子のスクリーニングを行った。Antibody array 解析において、ジェムシタビン暴露後に感受性株ではCalponinの発現上昇を認め、一方、耐性株においてはBcl-Xタンパク質の発現亢進が認められた。次にジェムシタビン暴露後のapoptosis誘導についてFlow CytometryとTunnel法を用いて解析を行った。感受性株のPC9と比べて耐性株のPC9/f14においては、Flow CytometryとTunnel法のいずれにおいても明らかにapoptosis誘導が抑えられていた。さらに耐性株においてBcl-X遺伝子発現をsiRNAにて抑制することでapoptosis誘導がなされ、ジェムシタビン感受性の改善が示されるかについて検討した。その結果、耐性株PC9/f14でBcl-X発現を抑制すると明らかにジェムシタビンの感受性が改善を示した。【結語】今回の解析でBcl-Xタンパク質の発現異常が、ジェムシタビン感受性に関わる因子一つである可能性が示唆された。

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開催年月日： 2006年11月

記述言語：日本語  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2006&ichushi_jid=J01244&link_issn=&doc_id=20061120260651&doc_link_id=%2Fec7jaluc%2F2006%2F004605%2F649%2F0614-0614%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fec7jaluc%2F2006%2F004605%2F649%2F0614-0614%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

開催年月日： 2006年11月

記述言語：日本語  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2006&ichushi_jid=J01244&link_issn=&doc_id=20061120260777&doc_link_id=%2Fec7jaluc%2F2006%2F004605%2F775%2F0646-0646%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fec7jaluc%2F2006%2F004605%2F775%2F0646-0646%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

開催年月日： 2006年11月

記述言語：日本語  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2006&ichushi_jid=J01244&link_issn=&doc_id=20061120260771&doc_link_id=%2Fec7jaluc%2F2006%2F004605%2F769%2F0644-0644%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fec7jaluc%2F2006%2F004605%2F769%2F0644-0644%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif