Faculty Profiles - RAI Kanmei

Papers - RAI Kanmei

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Programmed cell death-ligand 1 expression and efficacy of cisplatin-based chemotherapy in lung cancer: A sub-analysis of data from the two Okayama Lung Cancer Study Group prospective feasibility studies. Reviewed International journal

Kazuya Nishii, Katsuyuki Hotta, Kiichiro Ninomiya, Yuka Kato, Eiki Ichihara, Kadoaki Ohashi, Takashi Ninomiya, Toshio Kubo, Kammei Rai, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

Respiratory investigation 57 ( 5 ) 460 - 465 2019.9

Language：English Publishing type：Research paper (scientific journal)

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

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Re-administration of osimertinib in osimertinib-acquired resistant non-small-cell lung cancer. Reviewed International journal

Eiki Ichihara, Katsuyuki Hotta, Kiichiro Ninomiya, Toshio Kubo, Kadoaki Ohashi, Kammei Rai, Hisaaki Tanaka, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

Lung cancer (Amsterdam, Netherlands) 132 54 - 58 2019.6

Language：English Publishing type：Research paper (scientific journal)

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

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Actinomycosis-induced Trismus with Orbital Involvement. Reviewed

Daisuke Omura, Kammei Rai, Nobuchika Kusano, Fumio Otsuka

Internal medicine (Tokyo, Japan) 58 ( 1 ) 153 - 154 2019.1

Manifestation of Central Diabetes Insipidus in a Patient with Thyroid Storm. Reviewed

Akiko Nakamichi, Kazuki Ocho, Kosuke Oka, Miho Yasuda, Kou Hasegawa, Masaya Iwamuro, Mikako Obika, Kammei Rai, Fumio Otsuka

Internal medicine (Tokyo, Japan) 57 ( 13 ) 1939 - 1942 2018.7

Language：English Publishing type：Research paper (scientific journal)

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

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Far East Scarlet-like Fever Masquerading as Adult-onset Kawasaki Disease. Reviewed

Kazuki Ocho, Masaya Iwamuro, Kou Hasegawa, Hideharu Hagiya, Kammei Rai, Tetsuya Yumoto, Fumio Otsuka

Internal medicine (Tokyo, Japan) 57 ( 3 ) 437 - 440 2018.2

Language：English Publishing type：Research paper (scientific journal)

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

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Hypersensitivity Pneumonitis Caused by a Home Ultrasonic Humidifier Contaminated with Candida guilliermondii. Reviewed

Akemi Ando, Hideharu Hagiya, Takahiro Nada, Kosuke Kimura, Koichi Waseda, Kammei Rai, Yoshihisa Hanayama, Fumio Otsuka

Internal medicine (Tokyo, Japan) 56 ( 22 ) 3109 - 3112 2017.11

Language：English Publishing type：Research paper (scientific journal)

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

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nab-Paclitaxel in Combination with Carboplatin for a Previously Treated Thymic Carcinoma. Reviewed International journal

Go Makimoto, Keiichi Fujiwara, Hiromi Watanabe, Nobuhisa Kameyama, Mizuho Matsushita, Kammei Rai, Ken Sato, Toshiro Yonei, Toshio Sato, Takuo Shibayama

Case reports in oncology 7 ( 1 ) 14 - 7 2014.1

Language：English

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

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Diffuse parenchymal pulmonary amyloidosis showing an objective response to bortezomib-based chemotherapy. Reviewed

Hisao Higo, Keiichi Fujiwara, Hiromi Watanabe, Go Makimoto, Nobuhisa Kameyama, Mizuho Matsushita, Kammei Rai, Ken Sato, Tomoko Inomata, Kazutaka Sunami, Takuo Shibayama

Internal medicine (Tokyo, Japan) 53 ( 16 ) 1809 - 12 2014

Language：English Publishing type：Research paper (scientific journal)

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.

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A case of colorectal cancer with double-activating epidermal growth factor receptor mutations. Reviewed International journal

Kammei Rai, Keiichi Fujiwara, Mizuho Tsushima, Kenichiro Kudo, Makoto Mizuta, Kiyoshi Matsuo, Toshiro Yonei, Ichiro Yamadori, Katsuyuki Kiura, Toshio Sato

Japanese journal of clinical oncology 41 ( 9 ) 1138 - 41 2011.9

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

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

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Liposomal delivery of MicroRNA-7-expressing plasmid overcomes epidermal growth factor receptor tyrosine kinase inhibitor-resistance in lung cancer cells. Reviewed International journal

Kammei Rai, Nagio Takigawa, Sachio Ito, Hiromi Kashihara, Eiki Ichihara, Tatsuji Yasuda, Kenji Shimizu, Mitsune Tanimoto, Katsuyuki Kiura

Molecular cancer therapeutics 10 ( 9 ) 1720 - 7 2011.9

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

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

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術前補助療法進行非小細胞肺癌に対する導入化学放射線療法 Reviewed

枝園和彦, 豊岡伸一, 武本充広, 宗淳一, 山根正修, 大藤剛宏, 堀田勝幸, 頼冠名, 瀧川奈義夫, 田端雅弘, 木浦勝行, 三好新一郎

肺癌 50 ( 5 ) 472 - 472 2010.10

micro RNA 7発現プラスミドによるEGFR依存性腫瘍におけるin vivoでの著明な抗腫瘍効果(Dramatic anti-proliferative effect of designed miR-7 expressing plasmid against EGFR oncogene addicted tumors)

頼冠名, 瀧川奈義夫, 伊藤佐智夫, 木浦勝行, 清水憲二, 谷本光音

日本癌学会総会記事 69回 180 - 180 2010.8

EGFRチロシンキナーゼ阻害剤感受性株、耐性株に対するMicroRNA-7による腫瘍形成抑制効果の検討 Reviewed

頼冠名, 瀧川奈義夫, 伊藤佐智夫, 保田立二, 清水憲二, 谷本光音, 木浦勝行

肺癌 49 ( 5 ) 696 - 696 2009.10

局所進行非小細胞肺癌に対する集学的治療の現状と展望縦隔リンパ節転移を伴う非小細胞肺癌に対する術前放射線同時併用化学療法の治療成績 Reviewed

豊岡伸一, 木浦勝行, 武本充広, 山根正修, 大藤剛宏, 枝園和彦, 堀田勝幸, 頼冠名, 瀧川奈義夫, 田端雅弘, 佐野由文, 伊達洋至, 三好新一郎

肺癌 49 ( 5 ) 578 - 578 2009.10

ゲフィチニブ感受性および耐性細胞株の上皮成長因子受容体に対するMicro-RNA 7による抑制効果(MicroRNA-7 downregulates epidermal growth factor receptor in gefitinib resistant lung adenocarcinoma cells)

頼冠名, 瀧川奈義夫, 伊藤佐智夫, 木浦勝行, 保田立二, 清水憲二, 谷本光音

日本癌学会総会記事 68回 238 - 239 2009.8

Dual-time-point F-18 FDG PET/CT for evaluation of intrathoracic lymph nodes in patients with non-small cell lung cancer. Reviewed International journal

Takayoshi Shinya, Kammei Rai, Yoshihiro Okumura, Keiichi Fujiwara, Kiyoshi Matsuo, Toshiro Yonei, Toshio Sato, Kazuhiko Watanabe, Haruyuki Kawai, Shuhei Sato, Susumu Kanazawa

Clinical nuclear medicine 34 ( 4 ) 216 - 21 2009.4

Language：English Publishing type：Research paper (scientific journal)

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

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局所進行肺非小細胞癌に対する術前放射線同時併用化学療法の検討 Reviewed

枝園和彦, 豊岡伸一, 武本充広, 山根正修, 大藤剛宏, 堀田勝幸, 頼冠名, 瀧川奈義夫, 田端雅弘, 伊達洋至, 佐野由文, 木浦勝行

肺癌 48 ( 5 ) 428 - 428 2008.10

Leiomyoma of the trachea. Reviewed International journal

Hisayuki Shigematsu, Akio Andou, Kammei Rai, Ryohei Higashi

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 34 ( 3 ) 674 - 674 2008.9

Induction of lung adenocarcinoma in transgenic mice expressing activated EGFR driven by the SP-C promoter. International journal

Kadoaki Ohashi, Kammei Rai, Yoshiro Fujiwara, Masahiro Osawa, Seiki Hirano, Katsuyoshi Takata, Eisaku Kondo, Tadashi Yoshino, Minoru Takata, Mitsune Tanimoto, Katsuyuki Kiura

Cancer science 99 ( 9 ) 1747 - 53 2008.9

Language：English Publishing type：Research paper (scientific journal)

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

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[Treatment-refractory-dental-extraction-associated pyothorax involving infection by 2 species of oral originated bacteria requires surgical debridement by video assisted thoracoscopic surgery (VATS)]. Reviewed

Kammei Rai, Kiyoshi Matsuo, Toshiro Yonei, Toshio Sato

Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 82 ( 5 ) 461 - 5 2008.9

Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal)

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.

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