Papers by Akihiko Miyanaga
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Cancer Science, Mar 10, 2010
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Annals of Oncology, Jul 1, 2022
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Journal of Clinical Oncology, May 20, 2017
e21660 Background: Prospective and retrospective studies on intrapleural therapy of malignant ple... more e21660 Background: Prospective and retrospective studies on intrapleural therapy of malignant pleural effusion (MPE) have reported that the success rate for controlling pleural effusion was 50–70% at 2.5 months, and that the median post-pleurodesis survival time was 6-9 months. When pleurodesis is unsuccessful, and the lung is not fully expanded after drainage, the patients cannot receive effective chemotherapy. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of MPE. Here, a multicenter phase II trial was conducted to evaluate bevacizumab therapy in non-squamous non-small cell lung carcinoma patients with unsuccessful management of MPE. Methods: Non-squamous NSCLC patients with MPE who had received unsuccessful tube drainage or pleurodesis received chemotherapy with bevacizumab (15 mg/kg) every 3 weeks. The primary endpoint was Pleural effusion control rate (PECR), defined as the percentage of patients without reaccumulation of MPE for 8 weeks. The secondary endpoint was pleural Progression-free survival (PPFS), defined as PFS without reaccumulation of MPE. Results: Fifteen of 20 patients entered received a median of 4 cycles of carboplatin plus paclitaxel or pemetrexed including maintenance therapy with bevacizumab. The PECR was 80% of treated patients (95% CI: 78-82%). PPFS was 16.6 months (95% CI: 11.46-21.80 months). The response rate (RR) and disease control rate (DCR) were 45% (95% CI: 39.6-50.4%), and 80% (95% CI: 78.0-82.0 %), respectively, and the median PFS and overall survival (OS) were 9.8 months (95% CI: 4.38-15.28 months) and 19.6 months (95% CI: 4.38-15.28 months), respectively. Toxicities of grade ≥3 included neutropenia (50.0%), thrombocytopenia (10.0%), proteinuria (10.0%), hypertension (2.0%), pulmonary embolism (5%). Conclusions: The combination of bevacizumab with chemotherapy demonstrated efficacy with acceptable toxicities in controlling MPE in patients with non-squamous NSCLC whose MPE was unsuccessfully controlled by tube drainage or pleurodesis.
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PDF file - 117K, Supplementary Figure S2: Efficiency of transfection with miR134/487b precursors ... more PDF file - 117K, Supplementary Figure S2: Efficiency of transfection with miR134/487b precursors or miR-134/487 inhibitors.
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Journal of Nippon Medical School, 2014
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Oncology Reports, Sep 16, 2014
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Cancer Science, May 3, 2023
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PubMed, Apr 1, 2011
The most used standard therapy for malignant pleural effusion(MPE)is tube thoracostomy drainage, ... more The most used standard therapy for malignant pleural effusion(MPE)is tube thoracostomy drainage, except in cases where there are few pleural effusions or no symptoms. It has been reported that instilling an intrapleural agent is necessary for producing pleurodesis after tube thoracostomy drainage. To date, numerous chemical agents for the treatment of MPE have been studied. These include antibiotics, antineoplastic agents, biological response modifiers and others, that showed various degrees of chemical sclerosis. It was entered on a randomized comparison of tetracycline and bleomycin for treatment of MPE. The rate and time to recurrence were both significantly greater with bleomycin. In comparison, Talc was superior to bleomycin for control of MPE. Therefore, thoracoscopic pleurodesis with talc is now considered to be the gold standard treatment for MPE. However, talc has not been commercially available in Japan. We sought to evaluate the efficacy and toxicity of three intrapleural therapy regimens consisting of bleomycin, OK-432 or cisplatin plus etoposide(PE), for the management of malignant pleural effusion in previously untreated non-small cell lung cancer. The primary endpoint, pleural progression-free survival did not differ significantly between groups. Intrapleural treatment using OK-432 in the management of MPE was selected because it had the highest 4-week pleural progression-free survival rate and toxicity was tolerable. At present, OK- 432 is the standard agent used in Japan.
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Journal of Asthma, Jul 10, 2022
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PubMed, Aug 1, 2015
Tumor angiogenesis contributes to the development of tumor progression. Several vascular endothel... more Tumor angiogenesis contributes to the development of tumor progression. Several vascular endothelial growth factor(VEGF)-targeted agents, administered either as single agents or in combination with chemotherapy, have been shown to benefit patients with advanced-stage malignancies. In particular, bevacizumab is a humanized monoclonal antibody that specifically targets VEGF, inhibiting angiogenesis, thereby impeding tumor growth and survival. It is also possible that combined VEGF and the epidermal growth factor (EGFR) pathway blockade could further enhance antitumor efficacy and help prevent resistance to therapy. Preclinical and clinical studies have shown new various molecular targets and the functional characteristics of tumor angiogenesis, which may provide strategies for improving the therapeutic benefit.
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Japanese Journal of Clinical Oncology, May 9, 2019
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Scientific reports, Mar 31, 2024
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Lung Cancer, Dec 1, 2009
Bi-weekly administrations of nimustine hydrochloride (ACNU) plus paclitaxel were evaluated in thi... more Bi-weekly administrations of nimustine hydrochloride (ACNU) plus paclitaxel were evaluated in this phase II study in patients with refractory small cell lung cancer (SCLC). Patients who had disease progression within 3 months after treatment with irinotecan (CPT-11)-containing regimens were entered. They were treated with every other week administrations of ACNU 50 mg/m(2) plus paclitaxel 110 mg/m(2) on day 1 over 2 weeks. Twenty-four patients (20 males and 4 females, median age of 64 years, 17 patients with Eastern Cooperative Oncology Group [ECOG] performance status [PS] 0-1 and 7 patients with PS 2) participated in the trial. Of the 24 refractory patients after CPT-11 containing regimens, 17 patients had been given etoposide plus platinum. There were six partial responses, and an overall response rate of 25% (95% confidence interval, 10-46%) was obtained. The median time to progression and the median survival time after enrollment into this study were 2.8 and 5.8 months, respectively. The median overall survival from the first-line treatment was 19.5 months. The major toxicity was myelosuppression. Grade 4 neutropenia occurred in 13% of patients, and Grade 4 thrombocytopenia was observed in 13% of patients. There was one treatment-related death, attributed to pneumonitis. Bi-weekly administrations of ACNU plus paclitaxel provided a practical and well-tolerated regimen that was active for CPT-11-refractory SCLC.
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Molecular Cancer Therapeutics, Feb 1, 2014
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Molecular and Cellular Biology / Genetics, Aug 13, 2020
Background: The majority of pulmonary carcinoid (PC) tumors can be cured by surgical resection al... more Background: The majority of pulmonary carcinoid (PC) tumors can be cured by surgical resection alone, but a significant proportion of patients experience recurrence. As PC is insensitive to conventional chemotherapy and a significant proportion of patients develop metastases, further clarification of the molecular mechanisms of metastasis is needed in order to develop targeted therapeutics. Material and Method: We performed comprehensive whole-exome sequencing (WES) of primary tumors and corresponding normal lung tissues from 14 PC patients (including 4 patients who developed postsurgical distant metastasis) and RNA sequencing of primary tumors from 6 PC patients (including 4 patients who developed postsurgical distant metastasis). Exon array-based gene expression analysis was performed in 25 cases of PC. Results: We identified a total of 139 alterations in 136 genes. MUC6 and SPTA1 were recurrently mutated at a frequency of 21% (3/14) and 14% (2/14), respectively. Mucin protein family genes including MUC2, MUC4 and MUC6 were mutated in a mutually exclusive manner in 36% (5/14). Pathway analysis of the mutated genes revealed enrichment of genes involved in mitogen-activated protein kinase (MAPK) signaling, regulation of the actin cytoskeleton and focal adhesion, and transforming growth factor (TGF)-β signaling. RNA sequencing revealed a total of 8 novel fusion transcripts including one derived from a chromosomal translocation between the TRIB2 and PRKCE genes. All of the 8 fusion genes were detected in primary PCs that had developed metastasis after surgical resection. We identified 14 genes up-regulated in 5 PCs that had relapsed after surgical resection. Conclusions: In this study we identified novel somatic mutations and chromosomal rearrangements in PC by examining clinically aggressive cases that had developed postsurgical metastasis. It will be essential to validate the clinical significance of these genetic changes in a larger independent patient cohort. Citation Format: Akihiko Miyanaga, Mari Masuda, Noriko Motoi, Koji Tsuta, Yuka Nakamura, Nobuhiko Nishijima, Shun-ichi Watanabe, Hisao Asamura, Akihiko Tsuchida, Masahiro Seike, Akihiko Gemma, Tesshi Yamada. Whole-exome and RNA sequencing reveals chromosomal rearrangements associated with the recurrence of pulmonary carcinoid [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5892.
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Malignant pleural mesothelioma (MPM) is a rapidly fatal malignancy that is increasing in incidenc... more Malignant pleural mesothelioma (MPM) is a rapidly fatal malignancy that is increasing in incidence in Japan. In this study, we performed gene and microRNA (miRNA) expres¬sion profiling to identify novel therapeutic targets in MPM cells. Based on relative sensitivities to pemetrexed (PEM) and the histone deacetylase (HDAC) inhibitor, vorinostat (SAHA), 211H cells were determined to be the only sensitive MPM cell line out of the 6 tested. On the same series of cell lines, we performed whole genome transcriptomic profiling via DNA microarrays and pathway analysis of the derived data. Of particular note, IL-18 gene expression levels were signifi¬cantly higher in the cell lines that were either drug resistant or displayed intermediate sensitivity, compared to the sensitive 211H cell line. Pathway analysis revealed IL-18 as an impor¬tant gene associated with drug sensitivity of MPM cells. A relationship between IL-18 overexpression and drug resistance was also observed following targeted assessment of 10 cyto¬kine genes using quantitative RT-PCR. miRNA expression profiles were evaluated in the MPM cell line panel in order to discern the mechanism of IL-18 induction in the drug-resistant lines. We found that miR-379 and miR-411 belonged to the same cluster of miRNAs located on chromosome 14q32 that commonly target the IL-18 gene. Luciferase reporter assays revealed that miR-379 and miR-411 directly target the IL-18 gene. Introduction of miR-379 plus miR-411, as well as IL-18 silencing, significantly suppressed the invasive capacity of MESO1 cells in vitro. Furthermore, the use of either PEM or SAHA together with miR-379 plus miR-411 mimics mediated increased sensitivity to these drugs in MESO1 cells. These results suggest that the miR-379/411 cluster may provide new therapeutic opportunities for advanced MPM patients, depending on the nature of IL-18 gene expression. Citation Format: Akihiko Miyanaga, Masahiro Seike, Kazuo Yamamoto, Susumu Takeuchi, Rintaro Noro, Yuji Minegishi, Kaoru Kubota, Akihiko Gemma. miR-379/411 cluster regulates IL-18 and contributes to drug resistance in malignant pleural mesothelioma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 184. doi:10.1158/1538-7445.AM2015-184
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Japanese Journal of Clinical Oncology, May 9, 2016
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Papers by Akihiko Miyanaga