記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: A third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib, is the standard treatment for patients with non-small cell lung cancer harbouring mutant EGFR. Unfortunately, these patients inevitably acquire resistance to EGFR-TKI therapies, including osimertinib. However, the mechanism associated with this resistance remains unclear. METHODS: A 63-year-old Japanese female with lung adenocarcinoma underwent right upper lobectomy (pT1bN2M0 pStage IIIA, EGFR Ex21 L858R). She manifested post-operative tumour recurrence with multiple lung metastases 8 months later and began gefitinib treatment. The lung lesions re-grew 15 months later, and EGFR T790M mutation was detected in the lung metastasis re-biopsy. She was administered osimertinib; however, it relapsed with pleural effusion 16 months later. We isolated cells from the osimertinib-resistant pleural effusion to establish a novel cell line, ABC-31. RESULTS: Although the EGFR L858R mutation was detected in ABC-31 cells, the T790M mutation was lost. ABC-31 cells were resistant to EGFR-TKIs, including osimertinib. Phospho-receptor tyrosine kinase array revealed activation of the insulin-like growth factor 1 receptor (IGF1R), whereas overexpression of the IGF1R ligand, IGF2, induced IGF1R activation in ABC-31 cells. Combination therapy using EGFR-TKIs and IGF1R inhibitor acted synergistically in vitro. She was re-administered osimertinib since EGFR-TKIs and IGF1R inhibitor combination therapy was impossible in clinical practice. This had a slight and short-lived effect. CONCLUSIONS: Taken together, we have successfully established a new osimertinib-resistant lung adenocarcinoma cell line with activated IGF1R. These ABC-31 cells will help develop novel therapeutic strategies for patients with lung adenocarcinoma resistant to specific treatment via IGF1R activation.

DOI： 10.1093/jjco/hyab048

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Molecular agents targeting the epidermal growth factor receptor (EGFR)-, anaplastic lymphoma kinase (ALK)- or c-ros oncogene 1 (ROS1) alterations have revolutionized the treatment of oncogene-driven non-small-cell lung cancer (NSCLC). However, the emergence of acquired resistance remains a significant challenge, limiting the wider clinical success of these molecular targeted therapies. In this study, we investigated the efficacy of various molecular targeted agents, including erlotinib, alectinib, and crizotinib, combined with anti-vascular endothelial growth factor receptor (VEGFR) 2 therapy. The combination of VEGFR2 blockade with molecular targeted agents enhanced the anti-tumor effects of these agents in xenograft mouse models of EGFR-, ALK-, or ROS1-altered NSCLC. The numbers of CD31-positive blood vessels were significantly lower in the tumors of mice treated with an anti-VEGFR2 antibody combined with molecular targeted agents compared with in those of mice treated with molecular targeted agents alone, implying the antiangiogenic effects of VEGFR2 blockade. Additionally, the combination therapies exerted more potent antiproliferative effects in vitro in EGFR-, ALK-, or ROS1-altered NSCLC cells, implying that VEGFR2 inhibition also has direct anti-tumor effects on cancer cells. Furthermore, VEGFR2 expression was induced following exposure to molecular targeted agents, implying the importance of VEGFR2 signaling in NSCLC patients undergoing molecular targeted therapy. In conclusion, VEGFR2 inhibition enhanced the anti-tumor effects of molecular targeted agents in various oncogene-driven NSCLC models, not only by inhibiting tumor angiogenesis but also by exerting direct antiproliferative effects on cancer cells. Hence, combination therapy with anti-VEGFR2 antibodies and molecular targeted agents could serve as a promising treatment strategy for oncogene-driven NSCLC.

DOI： 10.1111/cas.14801

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: New therapeutic drugs have been developed for non-small cell lung cancer (NSCLC), and the prognosis of advanced NSCLC patients has improved. However, resistance to these drugs is a concern, and re-biopsy is necessary to determine the mechanism of drug resistance. There are many reports about the protocols for re-biopsy, including techniques such as bronchoscopy and computed tomography-guided needle biopsy (CTNB); however, there is no consensus on which method is optimal. Therefore, we retrospectively reviewed the bronchoscopy and CTNB re-biopsies conducted at our hospital. METHODS: We retrospectively analyzed 79 cases of re-biopsies with bronchoscopy or CTNB in patients with NSCLC from January 2014 to December 2016 at our institute. RESULTS: Forty-nine cases of bronchoscopy and 30 cases of CTNB were taken for re-biopsy. The diagnostic rates of bronchoscopy and CTNB were 83.7% and 100%, respectively (p = 0.023). The complication rates of bronchoscopy and CTNB were 18.4% and 36.7%, respectively (p = 0.11), with a statistically significant difference in the incidence of pneumothorax (0% vs. 23.3%, respectively; p < 0.01). Pneumothorax required drainage in 6.7% of all CTNB cases. There were no fatalities in either group. CONCLUSIONS: CTNB showed a higher diagnostic rate; however, it was associated with a higher rate of complications such as pneumothorax. Hence, the optimal modality must be determined individually for each patient.

DOI： 10.1016/j.resinv.2020.12.001

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Immune checkpoint inhibitors offer longer survival than chemotherapy in several clinical trials for advanced non-small cell lung cancer. In subset analyses of clinical trials, immune checkpoint inhibitors extended survival in patients aged ≥65 years, but the effects in patients aged ≥75 years are controversial. We performed multicenter, collaborative and retrospective analyses of immune checkpoint inhibitor efficacy and safety in non-small cell lung cancer patients aged ≥75 years. METHODS: We retrospectively studied 434 advanced non-small cell lung cancer patients who received immune checkpoint inhibitors from December 2015 to December 2017, and retrospectively applied the Geriatric (G) 8 screening tool with medical records. RESULTS: Of the 434 patients who received immune checkpoint inhibitors, 100 were aged ≥75 years. Five patients with performance status 3 were omitted from the final analysis. Immune checkpoint inhibitors were given as a first-line treatment to 20 patients. The objective response rates, median progression-free survival rates and median survival times were 35.0%, 6.1 months and 10.7 months for first-line treatment, and 20.0%, 2.9 months and 14.7 months for second- or later-line treatments, respectively. The median modified G8 score was 11.0. The median survival time was longer in the high modified G8 (≥12.0) group than in the low modified G8 (≤11.0) group (18.7 vs. 8.7 months; P = 0.02). Likewise, the median survival time was 15.5 months (performance status 0-1) vs. 3.2 months (performance status 2) (P < 0.01). The grade ≥ 2 immune-related adverse events incidence was 36.8%. CONCLUSIONS: In this study, immune checkpoint inhibitors were effective and tolerable for patients aged ≥75 years. The modified G8 screening tool and performance status were associated with the outcome of older non-small cell lung cancer patients treated with immune checkpoint inhibitors.

DOI： 10.1093/jjco/hyaa152

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is the standard therapy for non-small cell lung cancer (NSCLC) harboring EGFR mutations, but the resistance is inevitable. The drug-tolerant persister cancer cells are thought to be involved in the resistance. We recently reported that HER2 expression had a negative impact on time-to-treatment-failure in patients with EGFR mutant NSCLC. In this study, we hypothesized that HER2 might be a potential target for alternative combination therapy in NSCLC harboring EGFR mutations. In vitro study showed that the level of HER2 expression had no correlation with the sensitivity to EGFR-TKI, erlotinib but showed some correlation with HER2-inhibitor, ado-trastuzumab emtansine (T-DM1) in multiple EGFR-mutant lung cancer cell lines. In addition, HER2 expression was increased in persister cancer cells in 11-18 cell line harboring EGFR L858R or HCC827 cell line harboring EGFR exon 19 deletion after the exposure to erlotinib in vitro and in vivo. The combination of erlotinib and T-DM1 showed a superior inhibitory effect on cell proliferation compared with those of the erlotinib or T-DM1 alone in either 11-18 or HCC827 cells in vitro. The combination therapy also induced a significantly greater inhibitory effect on tumor growth in xenograft model in mice transplanted with either 11-18 or HCC827 cells compared with erlotinib alone or T-DM1 alone. No body weight loss was observed in these mice. These results suggested that the combination therapy with EGFR-TKI and T-DM1 might be a potentially promising strategy for treating lung cancer harboring EGFR mutations.

DOI： 10.1016/j.bbrc.2020.07.055

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Immune checkpoint inhibitors (ICIs) represent a paradigm shift in the development of cancer treatment. However, it remains to be clarified whether the benefits that they confer differ according to patient age. We conducted a systematic review and meta-analysis to assess age differences in the benefits of ICI treatment.Methods: We systematically searched the PubMed database for randomised controlled trials of ICIs, including PD-1, PD-L1 and CTLA-4 inhibitors across multiple cancer types, such as melanoma, lung cancer and gastric cancer. We extracted trials including hazard ratios (HRs) for death stratified by patient age (cut-off age, 65 years). The primary objective of this study was to assess the difference in ICI efficacy between younger and older patients. We calculated pooled HRs and 95% confidence intervals (CIs) for younger and older cancer patients, and assessed data heterogeneity.Results: We identified 3999 studies in our search. Of these, 24 eligible randomised trials, including a total of 8157 (57%) younger and 6104 (43%) older cancer patients, fulfilled the criteria for our study and were thus further analysed. The pooled HRs of the younger and older patients were 0.76 (95% CI: 0.69-0.84) and 0.80 (95% CI: 0.71-0.86), respectively; the difference in ICI efficacy between younger and older cancer patients was not significant (p = .82). Regarding the PD-1 and PD-L1 inhibitors, the survival benefit was similar in both age groups (HR: 0.74; p = .96), whereas for the CTLA-4 inhibitors, there tended to be less survival benefit for older versus younger patients (HR: 0.90 and 0.77, respectively; p = .26).Conclusions: The survival benefit conferred by ICI was not age-dependent, amongst patients aged 65 years or younger. However, age-dependent benefits may vary amongst different types of ICIs.

DOI： 10.1080/0284186X.2019.1695062

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The highly selective ALK receptor tyrosine kinase (ALK) inhibitor alectinib is standard therapy for ALK-positive lung cancers; however, some tumors quickly develop resistance. Here, we investigated the mechanism associated with rapid acquisition of resistance using clinical samples. METHODS: Autopsied samples were obtained from lung, liver, and renal tumors from a 51-year-old male patient with advanced ALK-positive lung cancer who had acquired resistance to alectinib in only 3 months. We established an alectinib-resistant cell line (ABC-14) from pleural effusion and an alectinib/crizotinib-resistant cell line (ABC-17) and patient-derived xenograft (PDX) model from liver tumors. Additionally, we performed next-generation sequencing, direct DNA sequencing, and quantitative real-time reverse transcription polymerase chain reaction. RESULTS: ABC-14 cells harbored no ALK mutations and were sensitive to crizotinib while also exhibiting MNNG HOS transforming gene (MET) gene amplification and amphiregulin overexpression. Additionally, combined treatment with crizotinib/erlotinib inhibited cell growth. ABC-17 and PDX tumors harbored ALK G1202R, and PDX tumors metastasized to multiple organs in vivo, whereas the third-generation ALK-inhibitor, lorlatinib, diminished tumor growth in vitro and in vivo. Next-generation sequencing indicated high tumor mutation burden and heterogeneous tumor evolution. The autopsied lung tumors harbored ALK G1202R (c. 3604 G>A) and the right renal metastasis harbored ALK G1202R (c. 3604 G>C); the mutation thus comprised different codon changes. CONCLUSIONS: High tumor mutation burden and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. Timely lorlatinib administration or combined therapy with an ALK inhibitor and other receptor tyrosine-kinase inhibitors might constitute a potent strategy.

DOI： 10.1016/j.jtho.2019.07.017

PubMed

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

researchmap

記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Cisplatin-based chemotherapy remains the mainstay treatment for advanced lung cancer; however, it remains controversial whether the efficacy of chemotherapy can be modulated by the immune-checkpoint status. In this study, we investigated the relationship between programmed cell death-ligand 1 (PD-L1) expression status and the efficacy of cisplatin-based chemotherapy by using individual patient data and pathological specimens obtained during our two previously performed prospective studies on the feasibility of short-term low-volume hydration in patients with advanced lung cancer who received cisplatin-based chemotherapy. METHODS: Among 91 patients who participated in the two aforementioned trials, those with assessable tumor specimens were included in this sub-analysis. PD-L1 expression levels were determined using immunohistochemical staining, while the Response Evaluation Criteria in Solid Tumors, version 1.1, were used for determining treatment efficacy. RESULTS: Thirty-two patients were investigated. PD-L1 expression was observed in 8 patients (25.0%; the PD-L1-positive group), with 2 exhibiting a PD-L1 expression of 50% or more. None of the patients in the PD-L1-positive group responded to treatment, while the overall response rate in the PD-L1-negative group was 20.8% (5 of 24; P = 0.296). Both the progression-free survival and overall survival rates were worse in the PD-L1-positive group than in the PD-L1-negative group (3.7 vs. 5.9 months [P = 0.018] and 5.8 vs. 37.3 months [P = 0.070], respectively). CONCLUSION: PD-L1 expression was negatively correlated with survival in patients receiving cisplatin-based chemotherapy.

DOI： 10.1016/j.resinv.2019.04.004

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Osimertinib is a tyrosine kinase inhibitor (TKI) that is an essential agent for the treatment of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). However, there is no established strategy for treatment following acquired resistance to this agent. One potential strategy for treating acquired resistance to EGFR TKIs is re-administration, which has been evaluated mainly using first- or second-generation EGFR TKIs. However, no clinical data are available with which to determine the significance of re-administration of osimertinib, a third-generation EGFR TKI. The aim of this study was to evaluate the efficacy of re-administering osimertinib to patients who had acquired resistance to this agent. PATIENTS AND METHODS: We reviewed the medical records of consecutive patients with advanced NSCLC harboring EGFR-activating mutations and secondary T790M, who had undergone osimertinib re-administration to treat acquired resistance. RESULTS: Seventeen patients were re-administered osimertinib after acquiring resistance to osimertinib. Of these, two received osimertinib to treat carcinomatous meningitis without any measurable lesion. Responses were evaluated in the remaining 15 patients. The objective response and disease control rates were 33% and 73%, respectively. Tumor shrinkage by osimertinib re-administration was associated with that due to initial osimertinib treatment (r = 0.585, 95% confidence interval [CI]: 0.104-0.844). In the remaining two patients without measurable lesions, one exhibited improved clinical symptoms following osimertinib re-administration. The median progression-free survival (PFS) time of all 17 patients was 4.1 months (95% CI: 1.9-6.7). The toxicity of re-administration was low, without interruption of the treatment due to adverse events (AEs). Most patients had grade 2 AEs or lower. CONCLUSIONS: Re-administration of osimertinib for EGFR-mutant NSCLC yielded modest activity with tolerable toxicity.

DOI： 10.1016/j.lungcan.2019.02.021

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2169/internalmedicine.1320-18

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We herein report a case of central diabetes insipidus complicated with thyroid storm. A middle-aged woman who was receiving treatment for Graves' disease suddenly complained of polydipsia, polyuria and general fatigue. Laboratory tests showed hyperthyroidism, hypernatremia, hypoosmolar urine and a decreased plasma vasopressin level. The occurrence of central diabetes insipidus with hyperthyroidism was revealed on the basis of pituitary magnetic resonance imaging, a water deprivation test and a desmopressin test. The clinical co-existence of diabetes insipidus and hyperthyroidism is very rare; however, the complication should be considered when hypernatremia and/or dehydration progress in patients with Graves's disease as a common autoimmune-related etiology.

DOI： 10.2169/internalmedicine.0063-17

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A previously healthy 31-year-old man was referred to us with refractory septic shock accompanied by bilateral conjunctival congestion and erythema of his right lower limb. Nine days after admission, he had bilateral desquamation of the fingertips, and his presentation satisfied the criteria for Kawasaki disease. A serological examination was positive for Yersinia pseudotuberculosis, and he was diagnosed with Far East scarlet-like fever (FESLF). Interestingly, his 11-month-old baby boy had similar symptoms around the same time, indicating the intrafamilial transmission of the pathogen. We should consider FESLF when we encounter a familial occurrence of systemic manifestations of Kawasaki disease.

DOI： 10.2169/internalmedicine.9250-17

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We herein report the first documented case of acute hypersensitivity pneumonitis in which Candida guilliermondii was the possible causative organism. A young Japanese woman presented to our hospital with relapsing respiratory symptoms accompanied by high fever. A detailed interview revealed that the onset of the symptoms occurred shortly after using a humidifier in her home. Her symptoms showed spontaneous improvement soon after admission, and an examination of her bronchoalveolar lavage fluid revealed the specific infiltration of inflammatory cells, which predominantly consisted of lymphocytes. Precipitin testing showed a positive reaction to C. guilliermondii, which was isolated from the home humidifier. Repeated history taking is essential for diagnosing occult respiratory disorders.

DOI： 10.2169/internalmedicine.9055-17

PubMed

researchmap

記述言語：英語  

We present the case of a 40-year-old man with previously treated thymic carcinoma, complaining of gradually worsening back pain. Computed tomography scans of the chest showed multiple pleural disseminated nodules with a pleural effusion in the right thorax. The patient was treated with carboplatin on day 1 plus nab-paclitaxel on day 1 and 8 in cycles repeated every 4 weeks. Objective tumor shrinkage was observed after 4 cycles of this regimen. In addition, the elevated serum cytokeratin 19 fragment level decreased, and the patient's back pain was relieved without any analgesics. Although he experienced grade 4 neutropenia and granulocyte colony-stimulating factor (G-CSF) injection, the severity of thrombocytopenia and nonhematological toxicities such as reversible neuropathy did not exceed grade 1 during the treatment. To our knowledge, this is the first report to demonstrate the efficacy of combination chemotherapy consisting of carboplatin and nab-paclitaxel against thymic carcinoma. This case report suggests that nab-paclitaxel in combination with carboplatin can be a favorable chemotherapy regimen for advanced thymic carcinoma.

DOI： 10.1159/000357938

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 77-year-old woman was admitted because of bilateral hand numbness and dyspnea on exertion. Her serum IgG was increased, and a bone marrow aspiration analysis supported a diagnosis of multiple myeloma. Additionally, computed tomography scans of the chest showed bilateral ground glass attenuations, linear opacities, and consolidations. Transbronchial lung biopsy revealed Congo Red-positive amorphous eosinophilic deposits. She was therefore diagnosed with diffuse parenchymal pulmonary amyloidosis accompanied by multiple myeloma. Following combination chemotherapy including bortezomib, her serum monoclonal protein levels were normalized, and pulmonary function and oxygenation improved.

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We describe the case of a 72-year-old woman with locally advanced lung tumor mimicking primary lung cancer. She was diagnosed with rectal cancer at the age of 65 years and was initially treated with platinum-based chemotherapy and thoracic irradiation as a treatment for primary lung cancer. One year later, a thyroid tumor was detected in her right thyroid lobe and was confirmed to have metastasized from rectal cancer based on pathological findings. Therefore, we suspected that she had metachronous double cancers and treated her with conventional chemotherapy for colorectal cancer. However, new life-threatening multiple lung metastases appeared. We treated her with the drug erlotinib because additional genetic analysis against primary lung tumor revealed typical double-activating epidermal growth factor receptor mutations. Histological review by immunostaining concluded that the primary lung tumor was composed of metastatic tumors from rectal cancer. In addition, genetic analysis revealed that the primary rectal cancer contained nearly the same types of double-activating epidermal growth factor receptor mutations as were present in the lung tumor. This is the first report of a case of rectal adenocarcinoma with double-activating epidermal growth factor receptor mutations.

DOI： 10.1093/jjco/hyr113

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have been strikingly effective in lung cancers harboring activating EGFR mutations. Unfortunately, the cancer cells eventually acquire resistance to EGFR-TKI. Approximately 50% of the acquired resistance involves a secondary T790M mutation. To overcome the resistance, we focused on EGFR suppression using microRNA-7 (miR-7), targeting multiple sites in the 3'-untranslated region of EGFR mRNA. Two EGFR-TKI-sensitive cell lines (PC-9 and H3255) and two EGFR-TKI-resistant cell lines harboring T790M (RPC-9 and H1975) were used. We constructed miR-7-2 containing miR-7-expressing plasmid. After transfection of the miR-7-expressing plasmid, using cationic liposomes, a quantitative PCR and dual luciferase assay were conducted to examine the efficacy. The antiproliferative effect was evaluated using a cell count assay and xenograft model. Protein expression was examined by Western blotting. The miR-7 expression level of the transfectants was approximately 30-fold higher, and the luciferase activity was ablated by 92%. miR-7 significantly inhibited cell growth not only in PC-9 and H3255 but also in RPC-9 and H1975. Expression of insulin receptor substrate-1 (IRS-1), RAF-1, and EGFR was suppressed in the four cell lines. Injection of the miR-7-expressing plasmid revealed marked tumor regression in a mouse xenograft model using RPC-9 and H1975. EGFR, RAF-1, and IRS-1 were suppressed in the residual tumors. These findings indicate promising therapeutic applications of miR-7-expressing plasmids against EGFR oncogene-addicted lung cancers including T790M resistance by liposomal delivery.

DOI： 10.1158/1535-7163.MCT-11-0220

PubMed

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The aim of this study was to evaluate the diagnostic capacity of F-18 fluorodeoxyglucose dual-time-point (DTP) positron emission tomography (PET)/computed tomography (CT) for intrathoracic lymph node (LN) metastases in patients with nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Thirty-four patients had DTP PET/CT, with 60 minutes and 2-hour scans (n=19, NSCLC; n=15, benign pulmonary disease). LN diagnoses were confirmed by surgery or clinical follow-up (n=14, metastatic LNs; n=45, nonmetastatic LNs; n=39, inflammatory LNs). RESULTS: The maximum standardized uptake value (SUVmax) in the metastatic group was significantly higher than those in the nonmetastatic and inflammatory groups on both early- and delayed-phase imaging (each P<0.0001). The retention index (RI) of SUVmax (RI-SUVmax) in the metastatic group was significantly higher than in the nonmetastatic (P=0.0008) and inflammatory groups (P=0.0074). No significant difference was found between SUVmax values of the nonmetastatic and inflammatory groups on early- (P=0.6461) or delayed-phase (P=0.6913), or between RI-SUVmax values of the nonmetastatic and inflammatory groups (P=0.5717). For early-phase SUVmax, the cut-off value for highest accuracy with metastatic LNs was 3.61, yielding a sensitivity of 86.67% and a specificity of 88.00%. For delayed-phase SUVmax, the cut-off value was 4.00, yielding a sensitivity of 91.6% and specificity of 92.9%. For RI-SUVmax, the cut-off value was 20.91%, yielding a sensitivity of 73.6% and specificity of 75.9%. CONCLUSIONS: DTP PET/CT with a semiquantitative technique may improve diagnostic capacity for nodal staging of NSCLC.

DOI： 10.1097/RLU.0b013e31819a1f3d

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ejcts.2008.05.025

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

To investigate the role of an activating epidermal growth factor receptor (EGFR) mutation in lung cancer, we generated transgenic mice expressing the delE748-A752 mutant version of mouse EGFR driven by the SP-C promoter, which is equivalent to the delE746-A750 mutation found in lung cancer patients. Strikingly, the mice invariably developed multifocal lung adenocarcinomas of varying sizes at between 5 and 6 weeks of age, and they died from tumor progression approximately 2 months later if left untreated. Daily oral administration of the EGFR tyrosine kinase inhibitor (TKI) gefitinib (5 mg/kg/day) reduced the total and phosphorylation levels of EGFR to those in wild-type mouse lung tissue; in addition, it abrogated tumor growth within 1 week and prolonged survival to >30 weeks. Interestingly, phosphorylated ErbB2, ErbB3, and thyroid transcriptional factor-1 increased in the transgenic mice compared with those in wild-type mice. They might play some roles in tumors progression in the transgenic mice. This model will be useful for studying the mechanisms of carcinogenesis, chemoprevention, and acquired resistance to EGFR TKIs in lung cancer patients carrying activating EGFR mutations.

DOI： 10.1111/j.1349-7006.2008.00875.x

PubMed

researchmap

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Cases of septic pulmonary embolism (SPE) diagnosed clinically by CT after dental extraction rarely include verification of bacteria from the local infection site. We report the case of a 70-year-old man without background disease suffering severe pyothrax after dental extraction. We detected two species of oral bacteria from his pleural effusion. Treatment was so difficult that it required surgical debridement by video assisted thoracoscopic surgery (VATS), even after the appropriate administration of antibiotics. According to the American Heart Association (AHA) prophylaxis guidelines for preventing infective endocarditis indicate that it is uncommon to prescribe antibiotics to patients without background disease after dental extraction. No appropriate Japanese guidelines exist considering the prevention of SPE causing severe pyothorax as in our case. The hematogenous spread of bacteria such as SPE caused by sepsis after tooth extraction thus requires more attended careful consideration in clinical practice if patients are to be properly protected against potentially serious complications.

PubMed

researchmap

記述言語：英語   出版者・発行元：(一社)日本癌学会  

researchmap

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 26-year-old woman visited the first hospital due to ascites in August 2003, She had continual abdominal pain diagnosed as Irritable bowel disease after a gastrointestinal and colon fiberscopy was performed. Chest-abdominal CT scan revealed normal chest, massive ascites and swollen ovary. To rule out malignancy, surgical biopsy was performed, which brought no significant findings. We focused on the high value of Adenosin deaminase (ADA) in ascites and strongly suspected tuberculotic peritonitis. Consequently, pathologist confirmed the existence of bacterial bodies stained by acid-fast stain after our consultation. Compared with the poor diagnostic accuracy of surgical biopsy, the value of ADA in ascites has a very high sensitivity and specificity. Considering the high risk of being infertile, to begin diagnostic medication of tuberculotic peritonitis is an acceptable choice for young women with a high value of ADA in the ascites.

PubMed

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

researchmap

記述言語：日本語   出版者・発行元：岡山医学会  

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

researchmap

記述言語：英語   出版者・発行元：(一社)日本癌学会  

researchmap

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.AM2019-2131

Web of Science

researchmap

記述言語：日本語   掲載種別：会議報告等   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

researchmap

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 CLINICAL ONCOLOGY  

DOI： 10.1200/JCO.2019.37.15_suppl.e23105

Web of Science

researchmap

記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

researchmap

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.AM2018-4818

Web of Science

researchmap

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.AM2018-1160

Web of Science

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)呼吸研究  

上皮成長因子受容体チロシンキナーゼ阻害薬(EGFR-TKI)に著効を示す臨床検体から発見されたEGFR変異のうち、exon 19 deletionとexon 21 L858Rはその約90%を占めている。筆者らの検討で、これらに相当する遺伝子変異を肺胞上皮細胞に特異的に発現させた遺伝子改変マウスは、ヒトに認められる肺腺癌に相当する腫瘍を生じた。変異EGFRは、mRNAおよび蛋白レベルで肺特異的に高発現し、その過剰リン酸化により、AKTやMAPKといったEGFR経路の下流に位置するシグナル蛋白の活性化が認められた。さらに代表的なEGFRチロシンキナーゼ阻害薬を投与したところ、1週間以内に腫瘍はほぼ完全に消失し、著明に生存期間が延長した。これはヒトにみられるEGFR変異による発がんをよく再現するものであった。この2モデルは未知の発がん機構および新規分子標的薬を、より臨床に近い形で解析するのに非常に有用であると考えられる。(著者抄録)

researchmap

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.AM2011-1158

Web of Science

researchmap

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.AM10-4041

Web of Science

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

researchmap

記述言語：英語   出版者・発行元：(一社)日本癌学会  

researchmap

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  

Web of Science

researchmap

記述言語：日本語   出版者・発行元：(一社)日本呼吸器外科学会  

researchmap

記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

researchmap

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2007&ichushi_jid=J01244&link_issn=&doc_id=20071019290166&doc_link_id=%2Fec7jaluc%2F2007%2F004705%2F166%2F0486-0486%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fec7jaluc%2F2007%2F004705%2F166%2F0486-0486%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif