19 results on '"Nakanishi, Yoichi"'
Search Results
2. Identification of Genomic Alterations Acquired During Treatment With EGFR-TKIs in Non-small Cell Lung Cancer
- Author
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KUBO, NAOKI, primary, HARADA, TAISHI, additional, SHIRAISHI, YOSHIMASA, additional, NOSAKI, KANAME, additional, NAKAGAKI, NORIAKI, additional, TAKESHITA, MASAFUMI, additional, OUCHI, HIROSHI, additional, IWAMA, EIJI, additional, TANAKA, KENTARO, additional, OKAMOTO, ISAMU, additional, SASAKI, HIROYUKI, additional, and NAKANISHI, YOICHI, additional
- Published
- 2019
- Full Text
- View/download PDF
3. A Novel Combination Therapy for Human Oxaliplatin-resistant Colorectal Cancer Using Oxaliplatin and Coxsackievirus A11
- Author
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WANG, BEIBEI, primary, OGATA, HISANOBU, additional, TAKISHIMA, YUTO, additional, MIYAMOTO, SHOHEI, additional, INOUE, HIROYUKI, additional, KURODA, MASAKI, additional, YAMADA, KAZUNARI, additional, HIJIKATA, YASUKI, additional, MURAHASHI, MUTSUNORI, additional, SHIMIZU, HIROYUKI, additional, OKAZAKI, TOSHIHIKO, additional, NAKANISHI, YOICHI, additional, and TANI, KENZABURO, additional
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- 2018
- Full Text
- View/download PDF
4. Prognostic Impact of PD-L2 Expression and Association with PD-L1 in Patients with Small-cell Lung Cancer
- Author
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TAKAMORI, SHINKICHI, primary, TAKADA, KAZUKI, additional, AZUMA, KOICHI, additional, JOGO, YUMIKO, additional, KINOSHITA, FUMIHIKO, additional, KOZUMA, YUKA, additional, MATSUBARA, TAICHI, additional, HARATAKE, NAOKI, additional, AKAMINE, TAKAKI, additional, TOYOKAWA, GOUJI, additional, HIRAI, FUMIHIKO, additional, TAGAWA, TETSUZO, additional, OKAMOTO, ISAMU, additional, NAKANISHI, YOICHI, additional, KAWAHARA, AKIHIKO, additional, AKIBA, JUN, additional, ODA, YOSHINAO, additional, and MAEHARA, YOSHIHIKO, additional
- Published
- 2018
- Full Text
- View/download PDF
5. PD-L2 Expression as a Potential Predictive Biomarker for the Response to Anti-PD-1 Drugs in Patients with Non-small Cell Lung Cancer
- Author
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TAKAMORI, SHINKICHI, primary, TAKADA, KAZUKI, additional, TOYOKAWA, GOUJI, additional, AZUMA, KOICHI, additional, SHIMOKAWA, MOTOTSUGU, additional, JOGO, TOMOKO, additional, YAMADA, YUICHI, additional, HIRAI, FUMIHIKO, additional, TAGAWA, TETSUZO, additional, KAWAHARA, AKIHIKO, additional, AKIBA, JUN, additional, OKAMOTO, ISAMU, additional, NAKANISHI, YOICHI, additional, ODA, YOSHINAO, additional, HOSHINO, TOMOAKI, additional, and MAEHARA, YOSHIHIKO, additional
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- 2018
- Full Text
- View/download PDF
6. Clinical Significance of PD-L1 Expression in Brain Metastases from Non-small Cell Lung Cancer.
- Author
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Takamori S, Toyokawa G, Okamoto I, Takada K, Kinoshita F, Kozuma Y, Matsubara T, Haratake N, Akamine T, Mukae N, Hirai F, Tagawa T, Oda Y, Iwaki T, Iihara K, Nakanishi Y, and Maehara Y
- Subjects
- Adult, Aged, Biomarkers, Tumor metabolism, Brain pathology, Brain Neoplasms mortality, Brain Neoplasms secondary, Carcinoma, Non-Small-Cell Lung mortality, Disease-Free Survival, ErbB Receptors genetics, Female, Humans, Lung Neoplasms mortality, Male, Middle Aged, Neoplasm Recurrence, Local pathology, Retrospective Studies, Smoking adverse effects, B7-H1 Antigen metabolism, Brain Neoplasms pathology, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms pathology
- Abstract
Aim: To investigate the association between positivity for programmed cell death-ligand 1 (PD-L1) in brain metastases (BM) and the prognosis or clinical factors in patients with non-small cell lung cancer (NSCLC)., Materials and Methods: Thirty-two patients with surgically resected brain-metastatic NSCLC were enrolled. The PD-L1 expression in BM was analyzed using the antibody against human PD-L1 (clone SP142). The PD-L1 positivity was defined as PD-L1 expression on brain-metastatic tumor cells of ≥5%., Results: Seven (21.9%) out of 32 patients showed PD-L1 positivity in BM. The PD-L1-positive BM group had a significantly shorter brain-specific disease-free survival than the PD-L1-negative BM group (p<0.05). PD-L1 positivity in BM was significantly associated with a heavy smoking history and the administration of radiotherapy for BM before surgery (p<0.05 and p<0.05, respectively)., Conclusion: The PD-L1 expression in BM from NSCLC may be associated with local recurrence following surgery, and the smoking- or radiotherapy-derived effects., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2018
- Full Text
- View/download PDF
7. Discrepancy in Programmed Cell Death-Ligand 1 Between Primary and Metastatic Non-small Cell Lung Cancer.
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Takamori S, Toyokawa G, Okamoto I, Takada K, Kozuma Y, Matsubara T, Haratake N, Akamine T, Katsura M, Mukae N, Shoji F, Okamoto T, Oda Y, Iwaki T, Iihara K, Nakanishi Y, and Maehara Y
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- Adrenal Gland Neoplasms genetics, Adrenal Gland Neoplasms pathology, Adrenal Gland Neoplasms radiotherapy, Adrenal Gland Neoplasms secondary, Adult, Aged, Brain Neoplasms genetics, Brain Neoplasms pathology, Brain Neoplasms radiotherapy, Brain Neoplasms secondary, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung surgery, Female, Gene Expression Regulation, Neoplastic, Humans, Jejunum pathology, Jejunum radiation effects, Male, Middle Aged, Neoplasm Metastasis, Splenic Neoplasms genetics, Splenic Neoplasms pathology, Splenic Neoplasms radiotherapy, Splenic Neoplasms secondary, B7-H1 Antigen genetics, Biomarkers, Tumor genetics, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung radiotherapy
- Abstract
Aim: To investigate the discordance in the programmed cell death-ligand 1 (PD-L1) expression between primary and metastatic tumors and analyze the association between the discordance and the clinical factors in non-small cell lung cancer (NSCLC) patients., Patients and Methods: Twenty-one NSCLC patients who underwent surgery or biopsy for paired primary and metastatic lesions at our Institution from 2005 to 2016 were analyzed. Lesions with the PD-L1 expression being ≥5% were considered PD-L1-positive., Results: The metastatic sites included the brain (n=16), adrenal gland (n=3), spleen (n=1) and jejunum (n=1). Negative conversion of the primary PD-L1-positive NSCLC and positive conversion of the primary PD-L1-negative NSCLC were observed in 3 (14%) and 2 (10%) cases, respectively. Radiotherapy for the metastatic brain lesion before its resection showed a significant relationship with the positive conversion of the primary PD-L1-negative NSCLC (p=0.048)., Conclusion: Radiotherapy-derived effects may contribute to the positive conversion of the primary PD-L1-negative NSCLC., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
8. DBA Lectin Binds to Highly Proliferative Mouse Erythroleukemia Cells.
- Author
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Swain A, Kulkeaw K, Tanaka Y, Nakanishi Y, Shirasawa S, and Sugiyama D
- Subjects
- Animals, Cell Line, Tumor, Leukemia, Erythroblastic, Acute, Mice, Protein Binding, Staining and Labeling, Transcriptome, Cell Proliferation, Plant Lectins chemistry
- Abstract
Background/aim: Hematopoietic malignancies lead to disease states involving abnormal proliferation of blood cells. Ki-67 and carboxyfluorescein succinimidyl ester (CFSE) are assays used to examine the proliferation status of cells but affect cell viability. In this study, we used lectins to bind to surfaces of proliferating cells with different phenotypes while preserving cell viability., Materials and Methods: The mouse lymphocyte Friend leukemia F5-5.F1 cell line was stained using biotin-conjugated lectins from Canavalia ensiformis (ConA), Dolichos biflorus (DBA), Erythrina cristagalli (ECA), Lens culinaris (LCA), Phaseolus vulgaris (PHA-E4), Arachis hypogaea (PNA), Ulex europaeus (UEA) and Triticum vulgaris (WGA) and sorted by fluorescence-activated cell sorting. Morphology, gene expression and proliferation assays were performed on sorted cells., Results: DBA, LCA and PHA-E4 probing sorted cells based on surface phenotype. Gene expression analysis showed that myelocytomatosis oncogene (Myc), cyclin D1 (Ccnd1), and cyclinD2 (Ccnd2) were more highly expressed in the DBA(High) fraction than DBA(Int) and DBA(Neg) fractions. Ki-67 expression and MTS assay correlated with the DBA-binding pattern, with DBA(High) reflecting the highest proliferative tendency., Conclusion: Labeling with DBA allows selection of proliferating cells using flow cytometry., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
- Published
- 2016
9. Biomimetic Peptides for the Treatment of Cancer.
- Author
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Mine Y, Munir H, Nakanishi Y, and Sugiyama D
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- Animals, Antineoplastic Agents therapeutic use, Biomimetics, Humans, Molecular Targeted Therapy, Neoplasms pathology, Peptides therapeutic use, Tumor Microenvironment drug effects, Antineoplastic Agents pharmacology, Neoplasms drug therapy, Peptides pharmacology
- Abstract
Cancer remains one of the leading causes of death worldwide, indicating that current cancer therapies are ineffective. Therefore, new treatments with high specificity and low toxicity are needed. Cancerous cells can be distinguished from normal cells based on expression of key proteins, namely surface proteins, scaffold proteins and signaling molecules. Moreover, cancer cells communicate with the tumor microenvironment consisting of a heterogenous population of cells, extracellular matrix components and soluble factors such as cytokines/chemokines and growth factors. Most therapeutic interventions have been designed to specifically target these proteins of interest. Biomimetic peptides (BPs) are artificially designed peptides that imitate the action of parent proteins or peptides. BPs can be classified into at least three types based on their target molecule: BPs that target (i) cell-surface molecules, (ii) intracellular molecules, and (iii) cancer cell-tumor microenvironment interactions. In this review, we analyze/discuss the current strategies for targeting tumors using BPs., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
- Published
- 2016
10. Aryl Hydrocarbon Receptor Antagonist StemRegenin 1 Promotes the Expansion of Human Promyelocytic Leukemia Cell Line, NB4.
- Author
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Koide R, Kulkeaw K, Tanaka Y, Swain A, Nakanishi Y, and Sugiyama D
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- Apoptosis drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Gene Expression drug effects, Gene Expression Regulation, Neoplastic drug effects, Humans, Leukemia, Promyelocytic, Acute, Receptors, Aryl Hydrocarbon metabolism, Up-Regulation, Purines pharmacology, Receptors, Aryl Hydrocarbon antagonists & inhibitors
- Abstract
Background/aim: StemRegenin 1 (SR1), an antagonist of aryl hydrocarbon receptor (AHR), reportedly promotes expansion of hematopoietic stem cells but its effect on leukemia cells is unclear. This study focused on the role of SR1 in leukemia cell proliferation., Materials and Methods: AHR expression was compared in the cell lines Jurkat, Kasumi-1, NB4 and K562, using real-time polymerase chain reaction. Highly AHR-expressing NB4 cells were cultured with SR1 for 2 and 4 days, and evaluated for viability and gene expression. DNA microarray was also performed., Results: The viability of NB4 cells treated with 1.5 μM SR1 increased at day 4. Expression of B-cell CLL/lymphoma 2 (BCL2) was up-regulated, while that of BCL2 associated X protein (BAX) was down-regulated at day 2. Increased cyclin D1 (CCND1), CCND2 and v-myc avian myelocytomatosis viral oncogene homolog (MYC) expressions were observed at day 4. Global gene expression profiles showed up-regulation of splice variant-related genes and down-regulation of inflammation-related genes., Conclusion: SR1 promotes the expansion of NB4 cells in vitro, implying the need for caution regarding in vivo use of R1., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
- Published
- 2016
11. Phase II Trial of Erlotinib in Elderly Patients with Previously Treated Non-small Cell Lung Cancer: Results of the Lung Oncology Group in Kyushu (LOGiK-0802).
- Author
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Yamada K, Azuma K, Takeshita M, Uchino J, Nishida C, Suetsugu T, Kondo A, Harada T, Eida H, Kishimoto J, Eriguchi G, Takayama K, Nakanishi Y, and Sugio K
- Subjects
- Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung mortality, ErbB Receptors genetics, Erlotinib Hydrochloride adverse effects, Humans, Lung Neoplasms mortality, Male, Mutation, Antineoplastic Agents therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Erlotinib Hydrochloride therapeutic use, Lung Neoplasms drug therapy, Protein Kinase Inhibitors therapeutic use
- Abstract
Background: As the incidence of lung cancer in the elderly is increasing worldwide, there exists a need to develop a clinically effective, less toxic therapy for this patient population. Although erlotinib has shown proven effectiveness against non-small cell lung cancer (NSCLC), few studies have prospectively investigated its application to elderly patients., Patients and Methods: Patients aged ≥75 years with advanced or recurrent NSCLC including wild-type EGFR who had previously received one or two chemotherapy regimens were enrolled in this trial. Erlotinib was initially administered at a dose of 150 mg/day orally until disease progression or unacceptable toxicities occurred. The primary endpoint was the objective response rate., Results: Forty patients were enrolled between May 2009 and January 2014. An objective response was observed in 8 patients (20%, 95%CI=9.1-35.7%), and the disease control rate reached 62.5% (95%CI=45.8-77.3%). After a median follow-up period of 12.2 months (range=1.4-47.2 months), the median progression-free survival period was 5.0 months (95%CI=2.3-7.6 months), and the median survival period was 12.2 months (95%CI=6.1-24.7 months). Major toxicities were skin disorders, fatigue, and anorexia. Most adverse events were grade 2 or less, but 13 patients (32.5%) required a dose reduction. Two patients developed interstitial lung disease, that was nevertheless reversible, and there were no treatment-related deaths., Conclusion: Although the percentage of patients requiring dose reduction seemed relatively higher than that in previous studies, erlotinib is a potentially useful therapeutic option for unselected elderly patients with previously treated advanced or recurrent NSCLC, as has been also shown for younger patients., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
- Published
- 2016
12. Aloe vera Extract Suppresses Proliferation of Neuroblastoma Cells In Vitro.
- Author
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Yonehara A, Tanaka Y, Kulkeaw K, Era T, Nakanishi Y, and Sugiyama D
- Subjects
- Animals, Cell Line, Tumor, Cyclin D2 genetics, Humans, Mice, RNA, Messenger biosynthesis, Aloe metabolism, Antineoplastic Agents pharmacology, Cell Proliferation drug effects, Neuroblastoma drug therapy, Plant Extracts pharmacology
- Abstract
Background/aim: Neuroblastoma is a pediatric solid tumor refractory to eradication by chemotherapy. To determine whether Aloe vera (AV), a pontial anticancer reagent, could be useful in neuroblastoma therapy, we investigated the anti-proliferative effects of an AV protein extract., Materials and Methods: Human neuroblastoma cell lines (IMR-32, TGW, CHP-126 and NBL-S) were cultured with AV protein extract and proliferation status was assessed by cell counting, Ki-67 staining and gene expression., Results: Among tested lines, the number of viable, AV-treated IMR-32 cells significantly decreased 1.98-fold by day 2 and 1.33-fold by day 5 of culture relative to untreated controls (p<0.05). Treatment also decreased the number of Ki-67(+) IMR-32 cells by 13% by day 5 (p<0.05) and, unlike untreated controls, CCND2 mRNA expression levels became undetectable by day 1., Conclusion: AV-protein extract suppresses human IMR-32 neuroblastoma cell proliferation, possibly by suppressing CCND2 transcript levels in vitro., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
- Published
- 2015
13. Apoptosis-inducing Factor, Mitochondrion-associated 2, Regulates Klf1 in a Mouse Erythroleukemia Cell Line.
- Author
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Kojima N, Tanaka Y, Kulkeaw K, Nakanishi Y, Shirasawa S, and Sugiyama D
- Subjects
- Animals, Apoptosis Regulatory Proteins genetics, Cell Line, Tumor, Mice, Oxidoreductases genetics, RNA Interference, RNA, Small Interfering, alpha-Globins biosynthesis, beta-Globins biosynthesis, Apoptosis genetics, Apoptosis Regulatory Proteins physiology, Erythropoiesis genetics, Kruppel-Like Transcription Factors biosynthesis, Leukemia, Erythroblastic, Acute metabolism, Oxidoreductases physiology
- Abstract
Background/aim: Apoptosis-inducing factor, mitochondrion-associated 2 (Aifm2), is a DNA-binding oxoreductase protein that promotes apoptosis. To assess its potential role in erythropoiesis we analyzed the effects of Aifm2 loss-of-function in the murine erythroleukemia line (MEL)., Materials and Methods: MEL cells were transfected with siRNA targeting Aifm2 for 24 h and evaluated by cell counting, flow cytometry with annexin V and PI staining and gene expression analysis., Results: Aifm2 knockdown did not affect the apoptotic status of MEL cells. However, Aifm2 knockdown significantly increased expression of the erythropoietic transcription factor Klf1 (2.9±0.2-fold, p<0.05) and decreased α- and β-globin expression (0.6±0.2-fold, p<0.05 and 0.5±0.2-fold, p<0.01)., Conclusion: Aifm2 may function in differentiation of erythroid MEL cells in vitro., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
- Published
- 2015
14. Dok2 likely down-regulates Klf1 in mouse erythroleukemia cells.
- Author
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Tanaka Y, Kulkeaw K, Inoue T, Tan KS, Nakanishi Y, Shirasawa S, and Sugiyama D
- Subjects
- Animals, Cell Line, Tumor, Down-Regulation, Gene Expression Regulation, Leukemic, Leukemia, Erythroblastic, Acute pathology, Mice, Promoter Regions, Genetic, Adaptor Proteins, Signal Transducing physiology, Kruppel-Like Transcription Factors genetics, Leukemia, Erythroblastic, Acute genetics, Phosphoproteins physiology
- Abstract
Background/aim: Docking protein 2 (Dok2) is an adapter protein which is involved in hematopoiesis. However, it still remains unclear how Dok2 functions in regulation of transcription of hematopoietic genes. To address this issue, we knocked-down Dok2 mRNA in mouse erythroleukemia cells which highly express Dok2 intrinsically., Materials and Methods: Mouse erythroleukemia cells were transfected with Dok2 siRNA for 24 h and gene expression of erythroid differentiation-related genes, such as GATA binding protein 1 (Gata1), Krüppel-like factor 1 (Klf1), α-globin and β-globin were assessed by real-time polymerase chain reaction., Results: Among the tested genes, expression of Klf1 exhibited a 1.94-fold increase when compared to the control 24 h after transfection. Immunocytochemistry and chromatin immunoprecipitation assays revealed that Dok2 protein localizes in the nucleus and binds to the promoter region of Klf1 gene., Conclusion: Dok2 is able to control Klf1 expression by transcriptional regulation through directly binding to its promoter region., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
- Published
- 2014
15. Multicolor analysis of cell surface marker of human leukemia cell lines using flow cytometry.
- Author
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Inoue T, Swain A, Nakanishi Y, and Sugiyama D
- Subjects
- Cell Line, Tumor, HLA-DR Antigens analysis, Humans, Leukemia pathology, Transcription Factors analysis, Antigens, Surface analysis, Flow Cytometry methods, Leukemia immunology
- Abstract
Background: Leukemia cell lines are utilized as tools for molecular analysis. Their implementation in therapy will require standards for quality control, including appropriate selection criteria for functional analysis and efficacy determination., Materials and Methods: Characteristics of six human leukemia cell lines -Kasumi-1, NB-4, MOLM-13, MV-4-11, K562, and Jurkat cells-were investigated using multiple color analysis of surface antigen expression and comparative analysis of gene expression., Results: Differentiation states of Kasumi-1 and MOLM-13 cells are colony-forming units-granulocyte/macrophage equivalent cells to myeloblasts with comparatively high Growth factor independent-1(GFI1) and Transcription factor PU.1 (PU.1) expression, respectively. NB4 and MV-4-11 express high levels of CCAAT/enhancer-binding protein-alpha (CEBPα) and differentiate from myeloblasts to pro-monocytes and myeloblasts, respectively. K562 cells are colony-forming units-erythroid equivalent cells to erythroblasts, with the highest expression of GATA-binding factor 2 (GATA2), GATA1 and Friend of gata-1 (FOG1). Jurkat cells are pro-T to mature T-cells with the highest Neurogenic locus notch-1 homolog protein 1 (NOTCH1) expression., Conclusion: Our study gives a useful guideline of standards for appropriate usage of leukemia cell lines for examining novel targets in vitro., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
- Published
- 2014
16. Kinase activity of protein kinase cα in serum as a diagnostic biomarker of human lung cancer.
- Author
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Kang JH, Mori T, Kitazaki H, Niidome T, Takayama K, Nakanishi Y, and Katayama Y
- Subjects
- Aged, Humans, Middle Aged, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Biomarkers, Tumor blood, Lung Neoplasms blood, Lung Neoplasms diagnosis, Lung Neoplasms enzymology, Protein Kinase C-alpha metabolism
- Abstract
Background: Recently, we reported on the existence of activated protein kinase Cα (PKCα) in blood and the possibility for its use in cancer diagnosis., Materials and Methods: In the present study, serum samples collected from patients with different lung cancer types (small-cell cancer, adenocarcinoma, and anaplastic cancer) were phosphorylated with a PKCα-specific peptide substrate and the phosphorylation ratio was detected by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry., Results: When 13 patient serum samples were phosphorylated with peptide substrates, phosphorylated peaks were obtained in eight samples. However, no peak associated with the phosphorylated peptide was observed using serum samples obtained from 10 healthy persons. Moreover, broadly used cancer biomarkers (progastrin-releasing peptide, carcinoembryonic antigen, and cytokeratin-19 fragment) were identified in eight samples among the 13 samples studied., Conclusion: These results suggest that serum activated PKCα is a reliable biomarker, applicable to lung cancer diagnosis.
- Published
- 2013
17. Adenovirus-mediated inhibitor kappaB gene transfer improves the chemosensitivity to anticancer drugs in human lung cancer in vitro and in vivo.
- Author
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Ni J, Takayama K, Ushijima R, Inoshima N, Uchino J, Harada T, Minami T, Takeshita M, Zhou C, and Nakanishi Y
- Subjects
- Adenoviridae genetics, Animals, Apoptosis, Caspase 3 metabolism, Cell Line, Tumor, Combined Modality Therapy, Drug Resistance, Neoplasm, Gene Transfer Techniques, Humans, Mice, NF-KappaB Inhibitor alpha, NF-kappa B metabolism, Paclitaxel pharmacology, Transfection, Vascular Endothelial Growth Factor A metabolism, Xenograft Model Antitumor Assays, Genes, p53, I-kappa B Proteins genetics, Lung Neoplasms therapy, NF-kappa B genetics
- Abstract
Background: Nuclear factor kappaB (NFkappaB) is a transcription factor which is importantly implicated in cancer cell growth. In a previous report, we confirmed that lung cancer cell growth was suppressed significantly by the blockade of NFkappaB function. In this study the combination effect of chemotherapy and inhibition of NFkappaB on the human lung cancer cell line, NCI-H460, in vitro and in vivo was investigated., Materials and Methods: In the in vitro experiment, 50% of cell growth inhibitory concentrations (IC50) of chemotherapy agents were determined alone or when combined with adenovirus mediated IkappaBalpha gene transfer. Annexin-V/PI stain and caspase 3 activity measurement were used to detect the apoptosis caused by treatment. In the in vivo experiment, the tumor growth suppressive effect of combination treatment was evaluated for tumor-bearing mice. NFkappaB, p53 and VEGF expression in the tumors were also analyzed immunohistologically., Results: Several chemotherapy agents, including paclitaxel, showed lower IC50s when combined with AdIkappaBalpha infection in vitro. Apoptosis through activation of the caspase 3 pathway was enhanced by the combination treatment. For established NCI-H460 tumors, combined treatment significantly inhibited tumor growth. Immunohistochemical staining showed increased expression of p65 after paclitaxel treatment, while paclitaxel in combination with AdIkappaBalpha intratumoral injection eliminated this expression accompanied by the slightly reduced expression of VEGF, with stable p53 status., Conclusion: A combination of chemotherapy and IkappaBalpha could inhibit tumor growth effectively by blocking the expression of NFkappaB and inducing apoptosis. Moreover, it might allow reduction of the dose of chemotherapy agents and provide benefit for clinical application.
- Published
- 2008
18. Immunohistochemical expression of MRP2 and clinical resistance to platinum-based chemotherapy in small cell lung cancer.
- Author
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Ushijima R, Takayama K, Izumi M, Harada T, Horiuchi Y, Uchino J, Hara N, and Nakanishi Y
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, Member 1 biosynthesis, Adult, Aged, Aged, 80 and over, Carcinoma, Small Cell drug therapy, Drug Resistance, Multiple physiology, Female, Gene Expression, Humans, Immunohistochemistry, Lung Neoplasms drug therapy, Male, Middle Aged, Multidrug Resistance-Associated Protein 2, Antineoplastic Agents therapeutic use, Carcinoma, Small Cell metabolism, Drug Resistance, Neoplasm physiology, Lung Neoplasms metabolism, Membrane Transport Proteins biosynthesis, Multidrug Resistance-Associated Proteins biosynthesis, Platinum Compounds therapeutic use
- Abstract
Determining an effective predictor of clinical drug resistance in small cell lung cancer (SCLC) is considered to be important. In this study, the relationship between the expression of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and MRP2, which are the members of ATP-binding cassette superfamily transporter, and of the p53 tumor suppressor gene and the response to chemotherapy were analysed. The expression of P-gp, MRP1, MRP2, and p53 was determined by an immunohistochemical analysis of transbronchial biopsy (TBB) specimens from 61 SCLC patients. The relationship of such expression was also investigated regarding chemotherapy and clinicopathological factors. The response rate in the MRP2-negative group was significantly higher than that in the MRP2-positive group (88% versus 50%). The P-gp-negative group responded significantly better to chemotherapy than the P-gp-positive group, with a response rate of 81% versus 39%. No relationship could be found between the response to chemotherapy and immunostaining for MRP1 or p53. In 37 patients treated with platinum-based chemotherapy, the response rate of patients in the MRP2-negative group was significantly higher than that in the positive group (92% versus 50%). In a multiple logistic regression analysis, MRP2 as well as P-gp were shown to be statistically significant predictors of chemotherapy resistance. These results suggest that immunostaining of MRP2 for TBB specimens may help to predict clinical resistance to platinum agents. This is the first report which indicates that the immunohistochemical expression of MRP2 is positively related to a clinical resistance to platinum.
- Published
- 2007
19. Gene transfer of inhibitor kappaB in human lung cancer cell line NCI-H460 inhibits tumorigenesis and angiogenesis in vivo.
- Author
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Ni J, Takayama K, Inoshima N, Uchino J, Harada A, Minami T, Harada T, Zhou C, and Nakanishi Y
- Subjects
- Adenoviridae genetics, Animals, Apoptosis genetics, Caspase 3, Caspases metabolism, Cell Growth Processes genetics, Cell Line, Tumor, Humans, I-kappa B Proteins biosynthesis, Immunohistochemistry, Lung Neoplasms blood supply, Lung Neoplasms pathology, Mice, Mice, Inbred BALB C, Mice, Nude, NF-KappaB Inhibitor alpha, NF-kappa B metabolism, Neovascularization, Pathologic genetics, Neovascularization, Pathologic pathology, Neovascularization, Pathologic therapy, Transfection, Vascular Endothelial Growth Factor A metabolism, Xenograft Model Antitumor Assays, Genetic Therapy methods, I-kappa B Proteins genetics, Lung Neoplasms genetics, Lung Neoplasms therapy, NF-kappa B antagonists & inhibitors
- Abstract
Background: Nuclear factor kappaB (NFkappaB) is an inducible and ubiquitously expressed transcription factor which is involved in cell survival, differentiation and growth and, thus, has also been implicated in tumor formation and development. Research on the effect of NFkappaB in inhibiting cancer cell growth, however, remains controversial., Materials and Methods: We investigated the effects of overexpressed IkappaBalpha on the proliferation of the human lung cancer cell line H460 in vitro and in vivo using IkappaBalpha-expressing adenovirus., Results: The results suggested that the infection of AdIkappaBalpha blocked NFkappaB activity in H460 cells and significantly inhibited cell proliferation by inducing apoptosis. An in vivo study showed the tumor incidence to be significantly lower in mice implanted with H460 cells infected with AdIkappaBa. For established H460 tumor, the intratumoral injection of AdIkappaBalpha also inhibited the tumor growth due to both a blockade of the NFkappaB activity and an inhibition of the VEGF expression., Conclusion: Adenovirus-mediated IkappaBalpha gene transfer is a promising cancer treatment strategy.
- Published
- 2005
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